Undergraduate Organic Chemistry Lab Manual...
This page intentionally left blank
Copyright © 2009, 2001, 1997, 1992, 1988 New Age International (P) Ltd., Publishers Published by New Age International (P) Ltd., Publishers All rights reserved. No part of this ebook may be reproduced in any form, by photostat, microfilm, xerography, or any other means, or incorporated into any information retrieval system, electronic or mechanical, without the written permission of the publisher. All inquiries should be emailed to
[email protected]
ISBN (13) : 978-81-224-2930-5
PUBLISHING FOR ONE WORLD
NEW AGE INTERNATIONAL (P) LIMITED, PUBLISHERS 4835/24, Ansari Road, Daryaganj, New Delhi - 110002 Visit us at www.newagepublishers.com
Dedicated to the everlasting memory of my departed parents
This page intentionally left blank
PREFACE TO THE FIFTH EDITION
The importance of a laboratory course attached to a theory course is undisputable in science subjects. Chemistry is a practical science and an appropriate correlation between teaching theory and practicals leads to a better understanding. My purpose of writing the earlier editions of the book indeed was to present a laboratory course which correlated with the lecture material. This fresh edition of the manual extends that concern. The overall organization of the book has essentially been retained as that of the fourth edition. An attempt has further been made to make necessary and useful inclusions in different chapters to make it more user friendly. The revised edition now consists of nine chapters instead of earlier eight. Chapter 7 has been divided into two separate chapters. All the chapters have been extensively revised and improved for clarity, accuracy and ease of performance of an experiment. Redundant material has been deleted. Throughout the book chemical reactions have been stressed wherever possible. Chapter 2 which deals with the basic laboratory equipment and techniques has been completely rewritten and expanded. The methods of distillations have particularly been revised to make them more practical. This time care has been exercised to include all the relevant tests and pertinent chemical reactions keeping in mind the chemicals that will be available in a laboratory. Chapters 5–6 concern the tests of compounds and preparation of the derivatives respectively. The derivatives selected are those that can be easily synthesized by simple chemical means, easy to isolate and purify. A method has been described to prepare the derivatives of unsaturated compounds normally the alkenes and the alkynes. More compounds have been included in the tables to cover a wide range of data of m.p. and b.p. This hopefully will assist the students in analysis and eventually identifying an unknown compound. Guidelines for the separation of binary mixtures of organic compounds are given. Chapter 7 in the earlier edition has been split into two chapters, for convenience. This is an obvious change in this edition. Chapter 7 now deals with estimations while Chapter 8 consists of organic preparations. Several changes have been introduced in these chapters. Chapter 7 has been reorganized and certain portions have been rewritten. Isolation and estimation of Vit C is a new inclusion. Chapter 8 deals with the methods of preparing organic compounds, some in a single step while many in multiple steps. A knowledge of reaction mechanism is important in organic chemistry. Therefore, an appropriate mechanism precedes the procedure for every preparation. Proper methods of handling equipment and chemicals, work-up of product, calculation of yields and precautions have been highlighted. Spectroscopy is one of the most valuable tools in the hands of an organic chemist. These methods offer a rapid and most accurate information about the compound under examination. Only two methods (I.R. and N.M.R.) are covered with appropriate examples in the last chapter. Virtually no change has been affected in this chapter.
viii
PREFACE
The logarithmic tables have been dropped. The diagrams have been redrawn. It is a very useful and handy book for all graduate and postgraduate level students. I am indebted to all those readers and users of this book who have laboured to send me their comments and suggestions from time to time. I will certainly welcome their feedback in future as well. I also wish to put on record my gratitude to the authors and publishers of books, monographs and articles whose hard work has immensely guided me in the preparation of this edition. It gives me a great pleasure to acknowledge the love and support of my wife during the preparation of this project. Finally, I gratefully acknowledge the collaboration and dedication of all professionals at the New Age International (P) Ltd., Publishers, New Delhi for the adept handling of this edition. Dr. Raj K. Bansal New Delhi
CONTENTS
Preface ................................................................................................................ vii 1.
SAFETY IN THE CHEMICAL LABORATORY ...................................... 17 1.1 1.2 1.3
1.4 1.5 1.6 1.7
2.
LABORATORY EQUIPMENTS AND TECHNIQUES ........................ 826 2.1 2.2 2.3
2.4 2.5 2.6
3.
Protective Clothing ................................................................................................. 1 1.1.1 Equipment and Apparatus ........................................................................ 2 Handling Chemicals ................................................................................................ 2 Flammable Materials .............................................................................................. 2 1.3.1 Corrosive and Toxic Reagents ................................................................. 2 1.3.2 Irritant and Lachrymatory Chemicals .................................................... 2 Eye Protection ......................................................................................................... 3 Disposal of Chemicals and Solid Wastes ................................................................ 3 Guidelines in Case of Accident or Injury ............................................................... 3 Toxicity and Hazards of Chemicals ........................................................................ 4
Glasswares ............................................................................................................... 8 Assemblies for Reactions ...................................................................................... 14 Distillation ............................................................................................................. 15 2.3.1 Simple Distillation .................................................................................. 15 2.3.2 Fractional Distillation ............................................................................ 18 2.3.3 Distillation Under Reduced Pressure .................................................... 20 2.3.4 Steam Distillation ................................................................................... 21 Crystallization ........................................................................................................ 23 Drying Agents ........................................................................................................ 25 Cleaning Apparatus ............................................................................................... 26
DETECTION OF ELEMENTS ............................................................... 2736 3.1 3.2 3.3 3.4 3.5 3.6 3.7
Physical State ........................................................................................................ Color ................................................................................................................. Odor ................................................................................................................. Acid or Base Character ......................................................................................... Ignition Test ......................................................................................................... Solubility ................................................................................................................ Elemental Analysis ................................................................................................
27 27 28 28 29 29 31
x
CONTENTS
4.
TESTS FOR FUNCTIONAL GROUPS ................................................. 3762 4.1 4.2
Alcoholic Group (ROH) ................................................................................................................. 37 Phenolic Group (AROH) ............................................................................................................... 40
4.3
Carbonyl Group
...................................................................................... 43
4.4
Carboxyl Group
.................................................................................. 49
4.5
Ester Group
4.6
Carbohydrates ........................................................................................................ 50
4.7
Nitro Group
4.8
Amino Group
(NH 2) ...................................................................................................................... 53
4.9
Amide Group
................................................................................... 56
4.10 Anilide Group
........................................................................................ 49
........................................................................................... 52
............................................................................... 57
4.11 Hydrocarbons ......................................................................................................... 58 4.12 Unsaturation
.................................................................................... 59
4.13 Carbonic Acid Derivatives ..................................................................................... 60
5.
TESTS FOR COMMON ORGANIC COMPOUNDS ......................... 63104 5.1 5.2 5.3 5.4 5.5 5.6 5.7 5.8
6.
Alcohols and Phenols ............................................................................................ 63 Carboxylic Acids ..................................................................................................... 73 Aldehydes and Ketones ......................................................................................... 80 Esters ................................................................................................................. 86 Amines ................................................................................................................. 90 Amides and Anilides .............................................................................................. 95 Aryl Halides ........................................................................................................... 98 Miscellaneous Compounds ...................................................................................101
PREPARATION OF DERIVATIVES ................................................ 105142 6.1
Derivatives of Alcohols .........................................................................................105
xi
CONTENTS
6.2 6.3 6.4 6.5 6.6 6.7 6.8 6.9 6.10
Derivatives of Phenols .........................................................................................107 Derivatives of Aldehydes and Ketones ................................................................108 Derivatives of Carboxylic Acids ...........................................................................109 Derivatives of Esters ............................................................................................111 Derivatives of Carbohydrates ..............................................................................111 Derivatives of Amines ..........................................................................................114 Derivatives of Hydrocarbons ...............................................................................115 Derivatives of Alkenes and Alkynes ...................................................................116 Physical Constants ...............................................................................................116 6.10.1 Melting Point .........................................................................................117 6.10.2 Boiling Point ..........................................................................................119 6.11 Separation of Binary Mixtures ............................................................................121 6.12 Physical Constants of some Common Organic Compounds and their Derivatives ...................................................................................................123
7.
ESTIMATION OF FUNCTIONAL GROUPS .................................. 143174 7.1 7.2 7.3
7.4
Estimation of the Number of Hydroxyl (OH) Groups in Alcohols ...................143 Determination of the Purity of Phenol ...............................................................145 Determination of Equivalent Weight of a Carboxylic Acid ...............................147 7.3.1 Silver Salt Method (Gravimetric Method) ............................................147 7.3.2 Volumetric Method ................................................................................148 Determination of Saponification Equivalent of an Ester ...................................149
7.5
Estimation of a Keto
7.6
Estimation of an Aldehyde
7.7 7.8 7.9
Estimation of Sulfur (Messengers Method) in Thiourea ..................................153 Estimation of Nitrogen (Kjeldahl Method) .........................................................154 Estimation of Amino (NH2) Group ......................................................................156
7.10 7.11 7.12 7.13 7.14 7.15 7.16 7.17 7.18 7.19 7.20
Estimation of the Number of Amide Groups .......................................157 Estimation of Glycine (Amino Acid) ....................................................................158 Determination of Percentage Purity of Glucose (A Reducing Sugar) ...............159 Estimation of Saponification Value of an Oil or Fat ..........................................161 Determination of Iodine Number of an Unsaturated Compound .....................162 Estimation of the Reaction Constant (H) .............................................................164 Determination of Chemical Oxygen Demand (COD) .........................................165 Estimation of Keto-Enol Equilibrium of a Keto Ester .......................................166 Determination of the Number of Methoxy (OCH3) Groups ..............................168 Determination of Ascorbic Acid Concentration ..................................................171 Determination of Molecular Weight of a Substance (Rasts Method) ...............173
Group ................................................................150 Group ......................................................151
xii
CONTENTS
8.
ORGANIC PREPARATIONS .............................................................. 175252 8.1
Electrophilic Aromatic Substitution Reactions ..................................................175 8.1.1 Preparation of Nitrobenzene (Nitration) .............................................176 8.1.2 Preparation of o- and p-Nitrophenols ...................................................178 8.1.3 Preparation of 2, 4, 6-Tribromoaniline (Bromination) ........................179 8.1.4 Preparation of Picric Acid (2, 4, 6-Trinitrophenol) ..............................179 8.1.5 Relative Rates of Electrophilic Aromatic Substitution ........................180 8.1.6 The Friedel-Crafts Reaction ..................................................................181 8.1.6 (a) Preparation of o-Benzoylbenzoic Acid (The Friedel-Crafts Reaction) .................................................................................................182 8.1.6 (b) Preparation of Diphenylmethane (The Friedel-Crafts Reaction) .................................................................................................183 8.1.6 (c) Preparation of >-Benzoylpropionic Acid (The Friedel-Crafts Reaction) .................................................................................................184 8.1.6 (d) Preparation of p-Xylene-2-Sulfonic Acid ...............................................185 8.2 The Diels-Alder Reaction .....................................................................................185 8.2.1 Preparation of 9, 10-Dihydroanthracene-9 10-=, >-Succinic Anhydride (The Diels-Alder Reaction) ..................................................185 8.3 The Beckmann Rearrangement ..........................................................................186 8.3.1 Preparation of Benzanilide ...................................................................186 8.4 The Perkin Reaction ............................................................................................187 8.4.1 Preparation of Cinnamic Acid ...............................................................187 8.5 The Cannizzaro Reaction .....................................................................................188 8.5.1 Base-Catalyzed Oxidation-Reduction of Benzaldehyde ........................188 8.6 The Fries Rearrangement ...................................................................................189 8.6.1 Preparation of 2, 5-Dihydroxyacetophenone .......................................189 8.7 The Schötten-Baumann Reaction ........................................................................190 8.7.1 Preparation of Benzanilide ...................................................................190 8.8 Benzilic Acid Rearrangement ..............................................................................191 8.8.1 Preparation of Benzilic Acid ..................................................................191 8.9 The Reimer-Tiemann Reaction ...........................................................................193 8.9.1 Preparation of Salicylaldehyde .............................................................193 8.10 Oxidation and Reduction ......................................................................................194 8.10.1 Preparation of Cyclohexanone (Oxidation) ..........................................194 8.10.2 Preparation of p-Nitrobenzoic Acid (Oxidation) ...................................195 8.10.3 Preparation of Anthraquinone (Oxidation) ..........................................196 8.10.4 Preparation of Adipic Acid (Oxidation) .................................................196 8.10.5 Preparation of Benzoic Acid (Oxidation) ..............................................197 8.10.6 Preparation of Trimethylacetic Acid (Oxidation) .................................198 8.10.7 Preparation of Ethylbenzene (The Wolff-Kishner Reduction) ............199 8.10.8 Preparation of Benzhydrol (Reduction) ................................................200 8.10.9 Preparation and Stereochemistry of Azobenzene (Reduction) ...........200
CONTENTS
8.11
8.12
8.13 8.14
8.15
8.16
8.17 8.18
8.19
8.20 8.21
xiii 8.10.10 Preparation of m-Nitroaniline from m-Dinitrobenzene (Reduction) .202 8.10.11 Reduction of p-Nitroacetophenone (Selective Reduction) ...................202 Organometallic Chemistry ...................................................................................203 8.11.1 Preparation of Benzoic Acid (The Grignard Reaction) ........................203 8.11.2 Preparation of Triphenylmethanol (The Grignard Reaction) .............204 8.11.3 Preparation of p-Toluic Acid from p-Bromotoluene ............................205 Dehydration ..........................................................................................................206 8.12.1 Preparation of Cyclohexene ..................................................................206 8.12.2 Preparation of Succinic Anhydride .......................................................208 8.12.3 Dehydration of Camphor Oxime (Molecular Rearrangement) ...........208 Optical Activity .....................................................................................................209 8.13.1 Resolution of Racemic =-Phenylethylamine ........................................210 Heterocyclic Compounds ......................................................................................211 8.14.1 Preparation of Quinoline (The Skraup Synthesis) ..............................211 8.14.2 Preparation of 2-Phenylindole (The Fischer-Indole Synthesis) .........212 8.14.3 Preparation of 1-Phenyl-3-Methyl-5-Pyrazolone .................................213 8.14.4 Preparation of 5-Hydroxy-1, 3-Benzoxazol-2-One ................................214 8.14.5 Preparation of 1, 2-Diphenyl-5-Nitrobenzimidazole ............................215 Diazotisation .........................................................................................................215 8.15.1 Preparation of p-Iodonitrobenzene .......................................................216 8.15.2 Preparation of p-Chlorotoluene (The Sandmeyer Reaction) ...............216 8.15.3 Preparation of o-Chlorobenzoic Acid (The Sandmeyer Reaction) ......217 Preparation of Dyes ..............................................................................................218 8.16.1 Preparation of Methyl Orange ..............................................................218 8.16.2 Preparation of Phenolphthalein ...........................................................219 8.16.3 Preparation of Fluorescein ...................................................................220 8.16.4 Preparation of Eosin ..............................................................................221 8.16.5 Preparation of Methyl Red ....................................................................221 The Pinacol-pinacolone Rearrangement .............................................................222 Chromatographic Methods ...................................................................................224 8.18.1 Column Chromatography ......................................................................225 8.18.2 Thin Layer Chromatography (TLC) .....................................................227 8.18.3 Paper Chromatography .........................................................................229 Polymerization ......................................................................................................230 8.19.1 Preparation of Phenol-Formaldehyde Resin .......................................231 8.19.2 Preparation of Thiokol Rubber .............................................................231 8.19.3 Polymerization of Styrene ....................................................................232 8.19.4 Preparation of Nylon-66 ........................................................................233 Catalytic Hydrogenation ......................................................................................233 8.20.1 Conversion of Cinnamic Acid to Hydrocinnamic Acid .........................233 Photochemical Reactions .....................................................................................235 8.21.1 Preparation of Benzopinacol .................................................................235 8.21.2 Photochemical Isomerization of Azobenzene ......................................236
xiv
CONTENTS
8.22 The Haloform Reaction ........................................................................................237 8.22.1 Preparation of Iodoform ........................................................................237 8.23 Isolation Experiments ..........................................................................................237 8.23.1 Isolation of Caffeine from Tea ..............................................................237 8.23.2 Isolation of Lycopene from Tomatoes ..................................................238 8.23.3 Isolation of Casein from Milk ...............................................................239 8.23.4 Isolation of Piperine from Pepper ........................................................239 8.23.5 Isolation and Estimation of Aspirin ......................................................240 8.24 Preparation of Triptycene ....................................................................................241 8.25 Addition of Dichlorocarbene to Cyclohexene......................................................242 8.26 Miscellaneous Preparations .................................................................................243 8.26.1 Preparation of Methyl Benzoate ...........................................................243 8.26.2 Preparation of Acetanilide (Acetylation) ..............................................244 8.26.3 Preparation of Aspirin (Acetylation) .....................................................244 8.26.4 Preparation of p-Nitroaniline ...............................................................245 8.26.5 Preparation of Mandelic Acid ................................................................247 8.26.6 Preparation of Anthranilic Acid ............................................................248 8.26.7 Preparation of Phenylurea ...................................................................249 8.26.8 Preparation of 2, 4-Dinitrophenylhydrazine ........................................249 8.26.9 Preparation of 7-Hydroxy-4-Methylcoumarin ......................................250 8.26.10 Preparation of Soap from Fat ...............................................................250 8.26.11 Preparation of p-Bromoaniline .............................................................251
9.
SPECTROSCOPIC METHODS ......................................................... 253267 9.1
9.2
Infrared Spectroscopy (i.r.) ..................................................................................253 9.1.1 Instrumentation .........................................................................................254 9.1.2 Preparation of Sample ...............................................................................254 9.1.3 Interpretation of Spectra ...........................................................................255 Nuclear Magnetic Resonance Spectroscopy (n.m.r.) ..........................................258 9.2.1 Instrumentation and Sample Handling ....................................................260 9.2.2 Interpretation of Spectra ...........................................................................262
Selected References .......................................................................................................269 Appendix 1 ...................................................................................................................................... 271 Appendix 2 ...................................................................................................................................... 273 Appendix 3 ...................................................................................................................................... 278 Appendix 4 ...................................................................................................................................... 279 Appendix 5 ...................................................................................................................................... 281 Appendix 6 ...................................................................................................................................... 282 Selected Journals .......................................................................................................................... 283 Index ................................................................................................................................................ 285
Chapter
1
SAFETY IN THE CHEMICAL LABORATORY
A chemist works in a chemical laboratory which consists of equipments, glasswares, hazardous chemicals, inflammable liquids, etc. Working with these materials is dangerous and consequently the occupation of a chemist is hazardous. A worker must thus create a safe environment to work in the laboratory. It is not only his or her life but of all others that is at risk, therefore, one must be particular about proper safety while working in the laboratory. There are certain guidelines which every one must follow to avoid any accident to himself or to fellow workers. All the persons working in the laboratory should learn simple safety rules through brochures, visual aids or manuals. Besides it is expected that each chemical laboratory is provided at least with a first aid box, fire extinguishers, fire alarm, waste disposal cans, shower, eye washer and a telephone. In the following pages several preliminary guidelines are summarized which should be observed at all times to minimize accidents and injuries while working in the laboratory.
1.1 PROTECTIVE CLOTHING One should enter the laboratory in proper clothing. Appropriate clothing is probably the first caution a worker need to take. A laboratory coat or apron should always be worn while working. Other protective clothing such as gloves and shoes should be used. Expensive clothing should not be worn as they may get damaged by splashing of harmful liquids. A laboratory coat provides enough protection in case of splashes and minimizes the contact of chemicals with the skin. Shorts and skirts should never be worn as they expose large areas of the skin. Special shoes are not necessary, however, using sandals, open-toed shoes and cloth shoes are not safe.
2
LABORATORY MANUAL OF ORGANIC CHEMISTRY
1.1.1 Equipment and Apparatus Equipment should not be handled unless one is sure it is functioning properly. All broken and cracked glasswares should be rejected. Before assembling the apparatus one should be acquainted with the different pieces. Instructor should always be asked when in doubt.
1.2 HANDLING CHEMICALS All chemicals are either dangerous, toxic, hazardous, inflammable or corrosive. If they are not handled rightly they can cause varying degrees of injuries. Acids, alkalies and bromine cause severe burns if brought in contact with the skin. Acetic anhydride and acetyl chloride bring tears to the eyes. Alcohols, benzene, carbon disulfide and ethers are highly inflammable. Diazo compounds, peroxides and azides are explosive. Silver nitrate, mercuric chloride, copper sulfate, etc., are considerably poisonous if taken internally by oversight. An exceptional precaution should be exercised in working with such chemicals. Always read the instructions on the label of the bottle before opening.
1.3 FLAMMABLE MATERIALS Always follow the general guidelines when using flammable materials or fire hazard chemicals and reagents. Solvents form a major part of the inflammable material commonly used in an organic chemistry laboratory. One should not heat a reaction flask containing a solvent using a burner. Such solvents should be distilled or evaporated on a steam bath, hot plate or sand bath. Alcohols, carbon disulfide, benzene, toluene, ether, etc., catch fire easily. Diethyl ether has a very low flash point and has a considerable narcotic effect. Some gases like hydrogen and certain solids such as Lithium aluminum hydride liberate hydrogen on reaction with water which is an extensively inflammable gas. Sodium and potassium undergo explosive reaction with water. Any excess sodium metal in sodium fusion should be destroyed in methanol and not in water.
1.3.1 Corrosive and Toxic Reagents Such reagents require special attention during their use. A corrosive reagent causes visible destruction of or irreversible chemical action at the site of contact. While working with such reagents gloves should be worn. In case of accidental spill or contact with the skin, the affected area should be washed immediately with liberal quantities of water. Phenol, bromine and various mineral acids cause severe burns. Mineral acids are also very corrosive. Toxic chemicals are very harmful on ingestion, inhalation or absorption by skin. These chemicals are also very hazardous to health. A list of hazardous chemicals is given in section 1.7.
1.3.2 Irritant and Lachrymatory Chemicals This class of compounds are highly lachrymatory, such as acid chlorides, thionyl chlorides and acid anhydrides.
SAFETY IN THE CHEMICAL LABORATORY
3
These affect the eyes and the respiratory system. In general, many low boiling compounds can also be listed under this category. These reagents should be handled in the fume hood.
1.4 EYE PROTECTION The human eye is the most valued sense organ and at the same time the most vulnerable because of its fragility. Protection of the eye is most important. Whenever possible eye hazards should be controlled at the source, for example, splashing of liquids, flying objects, enclosures to confine dust, vapors or fumes. Besides safety glasses must always be worn while performing an experiment. Ordinary glasses do not provide adequate protection since they do not have side shields, and also many may not have shatter-proof lenses. Do not look directly into the open mouth of a test tube in which a reaction is being conducted.
1.5 DISPOSAL OF CHEMICALS AND SOLID WASTES In general, a waste is considered hazardous if it is ignitable, corrosive, toxic or reactive. It can be considered that all chemical wastes generated in a chemical laboratory are hazardous. It is observed that waste chemicals if water soluble are simply poured down the drain accompanied with a large amount of tap water. Material not soluble in water is simply thrown out in the trash. All these create serious environmental problems nowadays. It is, therefore, the duty of everyone working in the laboratory not to dispose off the waste in a haphazard manner and thus risk the health of others. Organic solvents are used in plenty and many of them are miscible with water and are inflammable. These should not be thrown in the sink. Different labelled containers should be used for storing the solvents. If possible solvents like acetone, ethanol and benzene may be redistilled for reuse for cleaning purposes. Acids and alkalies should be neutralized before pouring them down the sink. A large amount of solid waste such as filter papers, drying agents, broken glasswares, chromatographic supports, cotton, aluminum foil, etc., is generated in the laboratory. These are non-toxic and should be packaged in suitable containers and disposed off. Toxic material, on the other hand requires special treatment before disposal. The instructor should be consulted on the procedure.
1.6 GUIDELINES IN CASE OF ACCIDENT OR INJURY The above guidelines are intended to prevent accidents in the chemical laboratory. However, in the event of an accident or injury one should know what to do. The first important point is one should not panic, the instructor is to be informed immediately and medical assistance called if necessary. Minor Cuts from broken glasswares are common in the laboratory. The cut should be thoroughly flushed under the tap and then covered with an appropriate bandage. If the cut is serious medical assistance should be sought. Similarly minor burns from hot equipment or chemicals are a constant hazard. Try not to touch hot glass. Wash the affected area with water and ask for medical assistance.
4
LABORATORY MANUAL OF ORGANIC CHEMISTRY
Burning Chemicals and Clothing from low boiling inflammable organic solvents is the most common fire hazard in the laboratory. If the fire is limited to a small container like a beaker then cover it with a wire gauze. Since all inflammable solvents are less dense than water, water should never be used to extinguish fire. Sand is often useful. For larger fires, a fire extinguisher is required which should be available in the laboratory. Learn the location and operation of a fire extinguisher. For fires beyond control, the fire alarm should be sounded and fire services summoned. In the event of ones clothes catching fire, the victim should roll over on the ground to extinguish the fire or should be covered with a fire blanket. A fire extinguisher should not be used on a person.
1.7 TOXICITY AND HAZARDS OF CHEMICALS In our daily life we handle chemicals in one form or the other whether it is in the laboratory or the house or contamination of the atmosphere. Most of these chemicals are inherently toxic and hazardous. Toxicity is the inherent property of a molecule to produce injury on reaching a susceptible site or in an organism. They harm by inhalation, ingestion or absorption by skin. They should, thus be handled with the utmost care to avoid threat to the health and life. For your own health and safety, exercise caution while handling chemicals and minimize your exposure to them. A brief description of the hazardous properties and effects on the human body of some basic chemicals is given below: Acetaldehyde: It is a gas at room temperature, b.p. 21oC, flammable and pungent smelling. The TLV* is 200 ppm. Inhalation of its vapors causes irritation of eyes, skin and respiratory organs. Acetaldehyde should be stored in a cool place. Acetic anhydride: It is a liquid b.p. 139.9oC, possess a pungent odor. It decomposes slowly with water to form acetic acid. The TLV is 5 ppm. Acetic anhydride irritates eyes, skin and mucous membrane and causes nausea. Acetonitrile: It is a colorless liquid, b.p. 81.6oC, possess aromatic odor and is toxic. It is flammable, TLV is 40 ppm, it causes acute headache, dizziness and nausea when inhaled. Acetyl chloride: It is a colorless fuming liquid, b.p. 52oC. With water, it decomposes violently to form acetic acid and hydrochloric acid. It is highly irritant and causes inflammation of skin. Store in well ventilated cool room. Acrolein: It is a colorless, flammable and pungent liquid, b.p. 59.7o C. TLV is 0.1 ppm. Its vapors cause inflammation of eyes, nose, skin and throat. Acrolein should be handled in a fume hood. Ammonia: Ammonia is colorless gas, b.p. 33.5oC. It has a sharp irritating odor and is soluble in most solvents. TLV is 50 ppm. Its inhalation may cause suffocation and damage to lungs. Ammonia is immensely irritant to skin and also causes nausea, cough, bronchitis and pulmonary endema. *TLV (Threshold limit value) is the concentration of an airbone constituent to which a worker may be repeatedly exposed without adverse effect for a normal 8 hr work day.
SAFETY IN THE CHEMICAL LABORATORY
5
Aniline: It is colorless oily liquid, b.p. 184 oC. It darkness on exposure to air. TLV is 5 ppm. It causes dizziness, nausea, abdominal pain and malaise. Benzene: It is a colorless to yellow liquid, b.p. 80oC and highly flammable. TLV is 10 ppm. Breathing benzene causes euphoria, headache, narcosis, dizziness and rapid heart rate. Long term exposure to benzene can affect the bone marrow and decrease red blood cells leading to anemia. Bromine: It is a dark raddish brown liquid, b.p. 58.8oC only slightly soluble in water. Bromine rapidly vaporizes at room temperature, the fumes are very irritating and is an extremely unpleasant chemical. TLV is 0.1 ppm. It causes skin burns, dizziness, headache, bronchitis and nausea. Store in a cool dry place and out of direct sunlight. n-Butanol: It is a colorless liquid, b.p. 177oC. It has a moderate fire risk. TLV is 100 ppm. On inhalation it causes respiratory inflammation, paralysis and dizziness. n-Butyl acetate: It is a volatile liquid with fruity odor, b.p. 126.5oC. TLV is 150 ppm. It causes conjunctivitis, cough, headache and anorexia (loss of appetite). n-Butyllithium: Commercially a stable solution of n-butyllithium is obtained in pentane or heptane. It is strongly irritant and toxic and ignities on contact with moist air. The solution should be preserved below 15 oC. Carbon disulfide: It is a colorless or faintly yellow liquid, b.p. 46 o C and very flammable. Carbon disulfide is a potentially fire hazard and toxic. TLV is 20 ppm. It causes headache, vomiting and abdominal pain. Carbon tetrachloride: It is colorless non-flammable heavy liquid, b.p. 77oC. TLV is 10 ppm. It has sweet odor and is toxic. Carbon tetrachloride causes irritation of eyes, headache, abdominal cramps and nervousness. Chlorine: It is a greenish-yellow gas having a suffocating odor. Chlorine is toxic and irritating. TLV is 1 ppm. Its inhalation causes irritation of eyes, difficult breathing, cough, pain, nausea and cyanosis. Chloroacetyl chloride: It is a colorless or slightly yellow liquid, b.p. 106 o C. Decomposes with water, and is non-combustible. It causes irritation of eyes, nose and throat. Chloroform: It is a colorless, heavy liquid, b.p. 61o C and possesses a sweet taste. It is volatile. TLV is 50 ppm. Chloroform causes unconsciousness, shortness of breath and vomiting. Diazomethane: It is a yellow gas at room temperature and soluble in ether. It decomposes explosively by water or alcohol. It possesses a severe explosion hazard. TLV is 0.2 ppm. Diazomethane is severely toxic and irritant. Diethyl ether: It is a colorless, very volatile and flammable liquid, b.p. 34.5oC. It has a very low flash point. It travels considerable distance to the source of ignition. TLV is 400 ppm. Ether has a penetrating smell. On inhalation it causes headache, vomiting, paralysis and irritation of respiratory tract. Store in a cool area.
6
LABORATORY MANUAL OF ORGANIC CHEMISTRY
1, 2- Dichloroethane: It is colorless oily liquid with chloroform like odor, b.p. 83o C. It is slightly soluble in water but flammable. TLV is 50 ppm. It causes irritation of respiratory tract, headache, weakness, anxiety and convulsions. Formaldehyde: It is a colorless gas with pungent odor, easily soluble in water. It is highly reactive and readily polymerizes with many organic substances. TLV is 3 ppm. Formaldehyde causes conjunctivitis, corneal burns and dermatitis. Hydrazine: It is a colorless, fuming liquid, b.p. 113.5o C. It has penetrating ammoniacal odor. It is highly dangerous. It has fire and explosion risk. TLV is 1 ppm. Hydrazine causes conjunctivitis, irritation of tracheal tract and skin as well as nausea. Hydrogen cyanide: It is a colorless gas possessing faint aromatic odor. It is miscible with water and alcohol. It is flammable and a fire hazard. TLV is 10 ppm. Hydrogen cyanide causes nausea, headache, palpitation, unconsciousness and death. Hydroxylamine : It constitutes of large white flakes or needles, m.p. 33o C. It is highly hygroscopic and unstable. It causes headache, dizziness, dispnea (difficult breathing), vomiting and jaundice. Iodine: It forms heavy, greyish black plates or granules, has a characteristic odor, m.p. 113.5oC. Iodine is soluble in alcohol, carbon disulfide, ether and chloroform. It causes headache, dizziness, cough, pulmonary endema and difficult breathing. Mercury: It is silvery and heavy liquid and has a low vapor pressure (0.002 mm/20 oC). TLV is 0.1 mg/m3. Swallowing causes burning in the mouth and throat, thirst, nausea and bloody diarrhea. Inhalation of mercury vapors cause inflammation of mouth, abdominal cramps, cough and fever. Phenol: It is a white crystalline mass but turns pink on exposure to air, b.p. 182oC. It absorbs moisture from the atmosphere and liquifies. TLV is 5 ppm. Phenol causes burns on contact with skin, pharynx, vomiting, cough and pulmonary endema. Phosgene: It is a colorless gas soluble in water forming pale yellow liquid and noncombustible. Phosgene is extremely toxic. TLV is 0. ppm. It causes headache, rapid respiration, cough, cyanosis, vomiting and pain in the upper abdomen. Phosphorus pentachloride: It is a yellow powder and sublimes at 160165o C without melting. It is flammable, TLV is 1 mg/m3. It causes irritation of eyes, bronchitis and nephritis (inflammation of kidney). Potassium cyanide: It is white amorphous powder. It has a faint almond-like odor. TLV is 5 mg/m3. It is immensely toxic. Pyridine: It is a slightly yellow or colorless liquid, flammable with nauseating odor, b.p. 115oC. TLV is 5 ppm. Pyridine causes conjunctivitis, pruitus (itching), eczema, headache, vomiting and abdominal pain. Styrene: It is a colorless to yellowish oily liquid with penetrating odor and sparingly soluble in water. Styrene readily undergoes polymerization. TLV is 100 ppm. It causes conjunctivitis, lack of appetite, nausea, weakness and drowsiness.
SAFETY IN THE CHEMICAL LABORATORY
7
Thionyl chloride: It is a pale yellow, pungent liquid, b.p 79oC. It is decomposed readily by water. TLV is 5 ppm. It causes conjunctivitis, dermatitis (skin inflammation) and pneumonia. Toluene: It is a colorless and flammable liquid with benzene like odor, b.p. 110.6oC. It is miscible with alcohol, chloroform, ether and acetone. TLV is 200 ppm. Toluene causes dermatitis, nausea, weakness and incoordination. Toluene is also known to cause cancer and nervous system disorders.
References 1. Hazards in the Chemical Laboratory, 4th edn., (Ed. by L. Bretherick), Royal Society of Chemistry, London (1986). 2. Prudent Practices for Handling Hazardous Chemicals in Laboratories, National Research Council, National Academy Press, Washington, D.C. (1981). 3. M.J. Pitt and E. Pitt, Handbook of Laboratory Waste Disposal, Wiley, New York (1985). 4. Sigma-Aldrich Library of Chemical Safety Data, 2nd edn., (Ed. by R.E. Lenga) (1988). 5. D.A. Pipitone, Safe Storage of Laboratory Chemicals, Wiley, New York (1991). 6. M.J. Lefevre, First Aid Manual for Chemical Accidents, Dowden et al., Stroudsberg, Pa (1980). 7. Safe use of Solvents, (Ed. by A.J. Collins and S.G. Luxon), Academic Press, New York (1982).
Chapter
2
LABORATORY EQUIPMENTS AND TECHNIQUES
In an organic chemistry laboratory a variety of glasswares and techniques are used for the synthesis, separation and purification of organic compounds as well as for routine work. The apparatus, however, becomes more sophisticated in a research laboratory. It is highly desirable that the student be familiar with the use and handling of the apparatus. The laboratory techniques described here are basic to almost all experimentation in organic chemistry.
2.1 GLASSWARES A brief discussion of the common types of glasswares and apparatus used in the chemical laboratory is given here.
(a) Flasks These are the common types of flasks used for a variety of purposes. Flasks (a) to (e) are employed for refluxing and distillation. Flasks with standard-taper ground glass joints and those without are in common use in a chemical laboratory. Flasks (a) and (b) are the ones with the ground glass joints. They require greasing and proper cleaning after use.
LABORATORY EQUIPMENTS AND TECHNIQUES
9
The Erlenmeyer flask (f) is used for mixing and titration. Figs. (g) to (i) represent different distillation flasks with condensers attached. The first two are the regular distillation flasks but (i) is called the Claisen flask with a fractionating column.
(b) Measuring devices The Pasteur pipette is used for transferring a small quantity of a solution or a liquid, while other pipettes deliver a fixed volume of the solution. The measuring cylinder (b) is used for measuring approximate volumes.
10
LABORATORY MANUAL OF ORGANIC CHEMISTRY
(c) Condensers The condensers (a) and (b) are used for refluxing and routine distillation. The air condenser (c) is employed if the liquid distilling has a very high boiling point.
(d) Funnels Figure (a) shows an long stem funnel used for transferring or filtering of liquids and reagent solutions, while (b) is the Hirsch funnel for filtering very small solid samples. Whereas (c) and (d) are the separatory funnels used for the extraction of a product from a reaction mixture; (e) is a dropping funnel employed for the addition of a reactant to a reaction flask.
LABORATORY EQUIPMENTS AND TECHNIQUES
11
During the extraction of a product while working with alkaline solutions it is observed that an emulsion is usually formed which prevents the separation of two immiscible layers. The emulsion so formed can be broken up by one of the following two methods. (i) Gently swirling the separatory funnel while holding it in an upright position. (ii) Saturating the aqueous layer of the reaction mixture with a salt such as sodium chloride. The second technique decreases the solubility of the inert organic solutes as well as the extraction solvents such as ether in the water layer. This process is referred to as the salting-out effect. The Buchner funnel and the Buchner flask are used extensively in synthesis for filtration of a solid product.
The arrangement for filtration (c) using a water pump or aspirator is shown in Figure (2.1):
Fig. 2.1: Apparatus for collection of crystals by suction filtration.
12
LABORATORY MANUAL OF ORGANIC CHEMISTRY
A water trap is included between the system and the water aspirator. This tends to prevent water sucking back into the apparatus when a sudden drop in pressure occurs. The vacuum generated depends on the speed of water rushing though the aspirator.
(e) Stirrers These figures represent various types of stirrers used for stirring purposes. These are usually made of glass but those made of stainless steel or teflon are also in common use. A stirrer is attached directly to a small electric motor with the aid of a small pressure tubing and mechanical agitation is achieved.
A magnetic stirrer on the other hand, is a useful device for small quantities and nonviscous reaction mixtures. The stirring is achieved by a magnetic spinner bar which is added to the reaction mixture.
Large scale and viscous reaction mixtures require a mechanical stirrer and need greater power of an external motor unit for turning a stirrer blade. A typical model is shown in fig. 2.2.
LABORATORY EQUIPMENTS AND TECHNIQUES
13
Fig. 2.2: A mechanical stirrer.
(f) Drying apparatus Tube (a) is usually packed with anhydrous calcium chloride and is used to exclude moisture from a reaction vessel. The drying tube is often used if the reaction needs to be performed under dry conditions. The vacuum desiccator finds application for drying a compound at low pressure.
14
LABORATORY MANUAL OF ORGANIC CHEMISTRY
The bottom of the desiccator may be filled either with anhydrous calcium chloride or conc. sulfuric acid. Sometimes, it is difficult to remove the moisture completely from a wet solid in a vacuum desiccator. In that case complete removal of moisture can be achieved using the Abderhalden drying pistol. The apparatus is shown in figure (c). In this case, the solid product is enclosed in a small boat (A) in a glass-stoppered drying tube (B). This tube is heated continuously by refluxing a suitably selected liquid (such as toluene) in the flask (C). The drying tube is connected to a chamber (D) containing an efficient desiccant. Both the drying tube and the desiccant chamber are evacuated by applying vacuum through the stopcock (E). On heating the solvent, the drying tube is surrounded by the hot vapors. The water vapors from the sample are captured by a chemical drying agent such as phosphorus pentoxide placed in (D).
(g) Adapters Adapters (a) and (d) are normally used to facilitate the delivery of a distillate from the condenser to a receiver. A vacuum can also be applied to adapter (d) if needed. Fig. (b) represents a simple distillation head while (c) is the widely used Claisen distillation head.
2.2 ASSEMBLIES FOR REACTIONS In figure 2.3 a round-bottomed flask is fitted with a water condenser. The joints could either be standard or instead a cork can be used to fix the condenser to the flask. This type of setup is employed for refluxing a reaction mixture. Boiling stones are always used to ensure smooth refluxing. A three-necked flask (b) equipped with a water condenser, dropping funnel and a mechanical stirrer with a mercury seal is the most common type of assembly used in synthesis. Mercury seal prevents the escape of gases during stirring. A drying tube can be fixed on the water condenser to exclude atmospheric moisture.
LABORATORY EQUIPMENTS AND TECHNIQUES
15
Fig. 2.3: Apparatus for carrying out reactions.
2.3 DISTILLATION Distillation is a classical technique in the laboratory for the purification of liquids from volatile and non-volatile impurities. It may also be used for the separation of two miscible liquids. The process of distillation may be described as the partial vaporization of a liquid and carrying over and condensation of these vapors back to liquid in a different part of the distillation apparatus. The distilled liquid is called the distillate, depending on the nature and boiling point of the substance to be distilled, different methods of distillation are employed in a chemical laboratory.
2.3.1 Simple Distillation Simple distillation is a laboratory method for the purification of organic solvents. All liquids possess vapor pressure which is always constant at a constant temperature. The vapor pressure is due to the tendency of the liquid molecules to escape from the surface of the liquid. This escaping tendency is different for different liquids. This causes a difference in the vapor pressure and hence the boiling point. For instance, ether evaporates rapidly
16
LABORATORY MANUAL OF ORGANIC CHEMISTRY
while glycerine does so slowly because the vapor pressure of ether is low. The vapor pressure increases with the increase in temperature. If the temperature is raised, the liquid starts boiling. The boiling point of a liquid is defined as the temperature at which its vapor pressure is equal to the external pressure. If the external pressure is 760 mm (i.e., the atmospheric pressure) a liquid starts to boil till its vapor pressure reaches this value. The presence of impurities lowers the vapor pressure and thus increases the boiling point. As stated above, vapor pressure increases as the temperature is raised. This is illustrated nicely in Fig. 2.4. As it is obvious when a pure substance is heated and if the temperature
Va po r p ress ure (a tm )
6 00
4 00
2 00
0
20
40
60
80
Fig. 2.4: The vapor pressure of a liquid versus temperature plot.
is raised, the vapor pressure of the substance becomes equal to the atmospheric pressure and the substance boils. For instance, water boils at 100oC when the external pressure is 760 mm (1 atm). Therefore, water has a vapor pressure 760 mm Hg at 100°C. Two liquids can be separated from one another provided their boiling points are not too close together. Usually the difference in boiling points should not be less than 70oC or more. The apparatus for carrying out a simple distillation is pictured in Fig 2.5. The assembly consists of a round-bottomed distillation flask equipped with a thermometer, a stillhead and a water condenser. Cold water is circulated into the condenser from the lower to upper end. The other end of the condenser is attached to a receiving flask through a receiving adapter. Normal grease is used for greasing the joints. The liquid (or the mixture of liquids) to be distilled is transformed to the distillation flask with the help of a funnel. The flask should not be filled with the liquid more than half. It is now heated with a proper heat source. A water or steam-bath is recommeded for low boiling solvents. An electrically heated oil-bath is needed for high boiling liquids. A Bunsen burner should never be used. Also avoid using a heating mantle, as the temperature is not controllable. The heating should be carried out slowly to prevent super heating of vapors, i.e., rise of temperature above the boiling point, and causing bumping. Bumping is the stage at which a periodically sudden ejection of excessive vapors takes place. At times it can become very dangerous.
LABORATORY EQUIPMENTS AND TECHNIQUES
17
Fig. 2.5: Apparatus for simple distillation.
Before heating the liquid 2-3 small boiling chips should be added to the distillation flask. A boiling chip is a small piece of porcelain tile. The escaping gas bubbles from the boiling chip will break the surface of the liquid and will promote smooth boiling and prevent bumping. The rising vapors of the liquid will pass through the neck of the flask, get condensed by the cold neck and drop back into the flask. This process will continue till an equilibrium is reached between the rising vapors and the condensing liquid. The vapors will then reach the thermometer and through the side tube into the condenser. Since cold water is being circulated through the condenser, the vapors will condense and collect by means of a curved adapter into the receiving flask. The temperature will remain constant till all the liquid has distilled. The impurities remain in the flask. The thermometer should not be immersed into the liquid because in that case, a temperature above the boiling point of liquid is recorded. To observe the correct boiling point, the thermometer be placed ideally in the vapors. The distillation of a liquid may be accomplished either at atmospheric pressure or under reduced pressure. In general, if the boiling point of the sample is above 180°C, then a reduced pressure distillation is recommended. In distillation, we often distill a mixture of two miscible liquids that form ideal solution. An ideal solution is sometimes defined as one which obeys Raoults law. However, there are a number of liquid mixtures that fail to obey this law. Such liquids may form an azeotrope. An azeotope or an azeotropic mixture is a mixture of definite composition that distills at a constant temperature as if it were a pure liquid. The boiling point of an azeotrope differs slightly in some cases from the boiling point of only one component. A familiar example is ethyl alcohol and water containing 95.5 percent ethyl alcohol and 4.5 percent water and boils at 78.15 °C whereas pure alcohol boils at 78.3°C. An azeotropic mixture cannot be separated by simple distillation.
18
LABORATORY MANUAL OF ORGANIC CHEMISTRY
Questions 2.1 What is the function of adding boiling chips to the liquid before heating? 2.2 Describe super heating. 2.3 If a liquid boils at a constant temperature over the whole range, could you conclude that it is pure? 2.4 Why is cold water circulated through a condenser from the lower to the upper end? 2.5 Could you record the correct boiling point if the thermometer tip is immersed into the liquid?
2.3.2 Fractional Distillation Simple distillation is employed for the separation of a binary homogeneous mixture of liquids whose boiling point difference is not less than 70°C. However, for a mixture of liquids with lesser difference in boiling points, separation can be effected by repeating the simple distillation several times. This process apparently is very cumbersome and time consuming. Alternatively, separation of such a mixture may be achieved by introducing a fractionating column. Fractional distillation is simply a method of accomplishing a whole series of repeated distillations into a single continuous operation. A fractionating column, in principle, is the elongation of the neck of the distilling flask which provides an extensive surface area for heat exchange at equilibrium conditions. There are several types of fractionating columns available. In a simple type glass beads or glass helics may be used as packing material in a pyrex glass tube. The packing may be supported by using a metal gauze. In other types indentations with downward slant in the side of the glass tube called Vigreaux column or the glass spiral of the Widmer column may be used. It is generally less effective than the packed column but is good for routine distillation.
LABORATORY EQUIPMENTS AND TECHNIQUES
19
A packed column provides a large surface area for efficient distillation. The efficiency of a column is expressed in terms of theoretical plates. A theoretical plate is the column within the column that is equal to a simple distillation. Therefore, a column with n theoretical plates is equal to n number of distillations. A fractionating column performs the function of several hundred distillations. The apparatus for fractional distillation is shown in Fig. 2.6.
Fig. 2.6: Apparatus for fractional distillation.
This assembly differs from that of simple distillation in that a fractionating column has been incorporated between the distilling flask and the stillhead. A boiling chip is added and the liquid is heated as usual in the distilling flask. The more volatile liquid vaporizes faster than the high boiling liquid, these vapors get condensed on the column packing. This continues and eventually the vapors get enriched in the lower boiling component. Equilibrations occur in all parts of the column and vapors that pass into the receiver are
20
LABORATORY MANUAL OF ORGANIC CHEMISTRY
those of the pure low boiling liquid. The residue in the flask is the high boiling liquid. The temperature remains constant till all the more volatile liquid has been distilled. The temperature than drops a little indicating one component of the mixture has been removed. More heat should be applied at this stage, and the second liquid commences to distill.
Questions 2.6 Define a theoretical plate. 2.7 Explain why a packed fractionating column is more efficient at separating a mixture of closely boiling liquids than an unpacked one. 2.8 If the rate of distillation through a packed column in too rapid, what will be its effect on the efficiency of separation?
2.3.3 Distillation Under Reduced Pressure A liquid boils when its vapor pressure equals the external pressure. Many organic compounds cannot be purified by distillation at ordinary pressure because they decompose when heated even below their known boiling points. Boiling point is dependent on external pressure, therefore, it can be reduced by reducing the pressure. Thus to make the purification of such substances possible they are distilled under reduced pressure. When the pressure is reduced, the substance boils at a lower temperature. This is known as distillation under reduced pressure or vacuum distillation. A vacuum of the order of 0.1 1.0 mm Hg can be obtained by using an oil immersion rotary vacuum pump. It is recommended that vacuum distillation be used if the normal boiling point is greater than about 150°C. An outfit for vacuum distillation is depicted in Fig. 2.7. Suitable standard joint flasks are used. Make sure the joints are greased properly using a good quality vacuum grease. A standard joint round bottom flask is fitted with a Claisen head which is attached to a water condenser. The condenser leads to a receiver consisting of four small round bottom flask usually called a pig through a receiver adapter which is connected to a vacuum pump. Different fractions are collected by simply rotating the adapter. A pressure measuring device is inserted between the vacuum pump and the adapter. The sample is introduced into the distilling flask and heated slowly to make sure that the boiling proceeds smoothly without bumping. A very fine capillary is inserted into the distilling flask to allow a thin stream of air bubble or nitrogen to the boiling liquid. The boiling chips do not work under vacuum. After the distillation is over, remove the heat source first and leave the apparatus to cool to room temperature before releasing the vacuum.
LABORATORY EQUIPMENTS AND TECHNIQUES
21
Fig. 2.7: (a) Apparatus for distillation under reduced pressure (b) Pressure measuring device.
Question 2.9 When 1-phenylethanol is purified by distillation, reduced pressure is always employed? Explain.
2.3.4 Steam Distillation Steam distillation is a method used for the separation of slightly volatile and water (steam) insoluble compounds from non-volatile compounds. It is particularly useful when the volatile component possesses a high boiling point and is likely to decompose if a direct distillation is attempted. This technique also makes possible separation and convenient purification of many light boiling compounds by low temperature distillation. A familiar example is the separation by steam distillation of a mixture of o- and p- nitrophenols obtained by nitration of phenol. A typical apparatus pictured in Fig. 2.8 is used for steam distillation.
22
LABORATORY MANUAL OF ORGANIC CHEMISTRY
Fig. 2.8: Apparatus for steam distillation.
Steam from the generator (or a steam line) is passed through a flask containing the mixture to be separated. The steam inlet tube extends to the bottom of the flask. This flask is also heated directly by a Bunsen burner. The flask is also fitted with a Claisen head and a stillhead. The stillhead contains the thermometer while its other end is attached to a condenser. Since the compounds distil along with water, it is essential to incorporate an adapter between the generator and the distilling flask. Steam also contains water, therefore, it should be removed before admitting the steam into the flask in order to prevent the volume of liquid in the flask which will become exceedingly large. After the distillation is over, the organic compound can be separated from the water-compound mixture in a separatory funnel. If the quantity of the compound is small, then it can be extracted with ether. The ether solution is dried with a drying agent and ether evaporated.
Questions 2.10 Describe the principle of steam distillation. 2.11 Can a mixture of salicyclic acid and p-dichlorobenzene be separated satisfactorily by steam distillation? Give reasons. 2.12 Would you expect bromobenzene to be purified by steam distillation?
LABORATORY EQUIPMENTS AND TECHNIQUES
23
2.4 CRYSTALLIZATION Crystallization is the most effective technique of purifying solid organic compounds. It is though not applicable to substances that react chemically with water. Products of organic reactions are seldom pure as they may be contaminated either with the starting material or some side-product. This will result in lowering of the melting point. Therefore, to obtain reasonably satisfactory physical constants, the substance needs to be purified. To accomplish this, different methods have been employed depending on the physical state of the organic compound. Distillation methods as described earlier are used for the purification of liquids. For solids, on the other hand, the technique of crystallization is employed. A solid substance is dissolved in a suitable solvent at its boiling point and then precipitated in a crystallized form on cooling. The substance is said to be crystallized and this process is referred to as crystallization. Crystallization depends on the differential solubility of a substance in a hot and a cold solvent. It is desirable that the solubility of the substance be high in the hot and low in the cold solvent. The glasswares shown below are frequently used in crystallization.
Purification by crystallization requires much skill and patience. A solvent is generally chosen in which the impurities are more soluble than the solid being purified. Selection of a solvent is not an easy matter though its selection is very important. The matter is simplified, if the substance is known, than the solvent for its crystallization has been reported. In this case one can look up the solvent in the literature. On the other hand, if the substance is new, a suitable solvent must be selected. The best way to find a solvent for a given compound is experimental trial. Different potential solvents may be tried by using a 2530 mg sample of the compound taken in a test tube. In many other cases, the selection of the rule like dissolves may be followed. According to the rule, a substance will dissolve in a solvent containing similar groups, or polar solvents will dissolve polar molecules and non-polar solvents will dissolve non-polar molecules. For instance, for hydrocarbons (nonpolar molecules) use hexane or pet ether. Those molecules containing polar groups such as etc. are more conveniently crystallized from hydroxylic polar solvents such as alcohol. Some general suggestions for selecting a solvent are listed in Table 2.1.
24
LABORATORY MANUAL OF ORGANIC CHEMISTRY
Table 2.1: Common Organic Solvents used for Recrystallization B.P. (°C)
Density
Water
100
1.00
Salts of organic compounds
95% ethanol
78
0.8
Alcohols, esters and acids
Acetone
56.2
0.792
Carbonyl compounds
Ethyl acetate
77.1
0.900
Carbonyl compounds
Diethyl ether
34.5
0.714
Ethers
Pet ether
30-60
0.601
Hydrocarbons and halo compounds
Ligroin
65-75
0.710
Hydrocarbons and halo compounds
Cyclohexane
80.7
0.799
Hydrocarbons
Methanol
65.0
0.791
Alcohols, esters and carboxylic acids
Solvent
Types of compounds that can be recrystallized
If a single solvent is not found satisfactory than a mixture of two solvents may help. The binary mixture of solvents is so chosen that the substance is soluble is one while insoluble in the other. In such a case, the compound is dissolved in one solvent on heating and to the hot solution, the other solvent is added dropwise with swirling the flask till a turbidity appears. At this stage a few drops of the first solvent are added till the solution becomes clear. Keep the solution undisturbed for crystallization. Samples to be crystallized often contain soluble extraneous coloring matter. Therefore, a small amount of activated charcoal, i.e., Norit should be added to the solution and boiled for a few minutes. The amount of charcoal should be kept to a minimum as some of the desired product is invariably absorbed on charcoal. The solution is filtered while still hot to minimize evaporation of the hot solution during filtration. If this is not done, the solvent is likely to crystallize on the filter paper. The filtrate is cooled slowly at first and then in an ice-bath if necessary. Slow cooling of the solution is necessary because it will result in large crystals. Rapid cooling and stirring will lead to smaller crystals. The size of the crystals depends on the rate of cooling. It may be pointed out that rapid formation of solid material amounts to precipitation and is not exactly the same as crystallization. If after cooling the solution, no crystals appear, then it is wise to induce crystallization by adding a few seed crystals of the pure substance already available to the solution. This will provide a nucleus for the crystals to grow, this process is called seeding. If this fails, alternatively the sides of the container may be scratched with a glass rod. This process proves effective in inducing crystallization. But if this also fails then probably there is too much solvent which should be removed by boiling and the remaining solution cooled again. Finally, the solution may be cooled in dry ice-acetone bath if all these attempts fails. If the compound is incapable of crystallization, some other technique such as chromatography may prove helpful.
LABORATORY EQUIPMENTS AND TECHNIQUES
25
After the crystallization is complete, the crystals are filtered in a small Buchner funnel. The filtrate or the solution remaining after the removal of crystals is called the mother liquor. This also contains a significant quantity of crystals. Some solvent may be evaporated from this solution and the remaining solution left for crystallizations to obtain a second crop of the substance. Crystals from mother liquor are almost always somewhat less pure than the crystals which separate first. The crystals are then freed of adhering solvent. For this the crystals are pressed between the folds of filter paper and squeezed. They are then transferred to a clean watch glass. Crystals may be dried in air at room temperature or in a vacuum desiccator. Small samples can be dried in an Aberhalden pistol. The melting point of the substance is finally determined. Two or more crystallizations may be necessary in some cases if a satisfactory melting point is not obtained of the crystallized sample.
Questions 2.13 How is colored product decolorized from a preparation? 2.14 During crystallization, the solution should not be rapidly cooled in ice. Why? 2.15 What objection might be offered to the use of a particularly drying agent in the case listed below: (a)
Calcium chloride for aniline.
(b)
Phosphorus pentoxide for isopropyl alcohol.
(c)
Potassium hydroxide for methyl butyrate.
2.16 Would you recommend suction filtration for a solution in which petroleum ether is the solvent? 2.17 How does the size of crystals depend on the rate of cooling of the solution? 2.18 What is the affect of impurities on the melting point of a compound? 2.19 During recrystallization the solution should not be suddenly cooled in ice. Why?
2.5 DRYING AGENTS It is necessary to dry organic reaction products before further analysis is undertaken. Presence of moisture not only affects the melting point and boiling point but also the success of the subsequent reactions. Solids are normally dried either in air or in a vacuum desiccator. For drying solutions of organic compounds different types of drying agents are employed. These agents either react with water or form a hydrate with it. An ideal drying agent should not react with the organic liquid and be easily separated by filtration from the dried liquid. The agents most often used are anhydrous salts which form hydrates with water and some of these are described below: Calcium sulfate (CaSO4) : It is also known as drierite. It is extremely fast and very efficient drying agent. However, calcium sulfate has a low capacity as two molecules of
calcium sulfate combine with only one molecule of water (2CaSO4 . H2O) to form the hydrate.
26
LABORATORY MANUAL OF ORGANIC CHEMISTRY
Magnesium sulfate (MgSO 4) : It is a good drying agent and forms heptahydrate (MgSO4 . 7H2O). This is probably the most satisfactory reagent for general drying purposes. Besides, it is also cheap. Sodium sulfate (Na2SO4): It is a high capacity reagent but possesses low action and efficiency. It combines with seven and ten molecules of water, and is recommended for removal of water, especially from ether solution of organic compounds. It is less efficient than MgSO4. Calcium chloride (CaCl2) : It is good in terms of both intensity and capacity, though, it cannot be used to dry amines, alcohols, phenols, acids and esters. It is good for halides and hydrocarbons. Potassium carbonate (K2CO3): It is a basic drying agent and is fairly good. It reacts with two molecules of water. It is good for oxygen and nitrogen containing compounds. Potassium hydroxide (KOH): It is a basic drying agent. Phosphorus pentoxide (P2O5): It is an acidic drying reagent. The dried solution can be distilled from the drying agent.
2.6 CLEANING APPARATUS It is very essential that clean glasswares be used for carrying out a reaction. Presence of impurities may have an adverse effect on the desired reactions as well as the purity of the final products. Every piece should be properly washed and dried. Normally any kind of a popular brand of washing powder may be used. But if the apparatus is boiled with a tarry material, then it can be dislodged with a small quantity of commercial acetone or special washing solutions such as chromic acid solution. After this the apparatus should be rinsed with water and washed with soap solution and finally again with water. For drying an electric oven may be used.
Chapter
3
DETECTION OF ELEMENTS
In qualitative organic analysis the principal concern is with the detection and identification of unknown organic compounds. The unknown may be a solid or liquid. The process of identification involves a series of steps that help to establish the identity of the unknown compound. The analysis commences with certain preliminary tests which offer the worker certain clues about the type and class of compound under examination. Any conclusion drawn, however, depends on ones chemical intuition and experience. A systematic analysis of detecting the elements is initially carried out which enables a rational choice of subsequent tests to be performed. It is thus advisable to start with the determination of physical properties and the types of elements present in the unknown compound.
3.1 PHYSICAL STATE The physical state of the unknown compound whether it is a solid or liquid should be indicated as a preliminary examination. The former is somewhat easier to handle than the latter. A solid sometimes becomes wet on keeping because of its hygroscopic nature. This can also happen when two solids are powdered together. After a careful examination of the shape and color of the crystals it may be possible sometimes to determine whether the unknown is single or a mixture of two components. Handle the chemicals with care and never taste anything.
3.2 COLOR Note the color of the unknown compound. Not many organic compounds are colored. A colored sample, therefore, may be characteristic of certain groups of substances or functional group present in the unknown. The color of a compound is attributed to the presence of
28
LABORATORY MANUAL OF ORGANIC CHEMISTRY
chromophoric groups such as NO2, NH2, C O, N N, etc. When such groups are introduced into a molecule, absorption maxima are shifted towards the visible region and the substance appears colored. Many simple phenols, however, attain color on keeping because of atmospheric oxidation. Some examples of typically colored compounds are given below: Table 3.1: Typical Colors of Some Organic Compounds Compound
Color
p-Nitrotoluene
Lemon
o-Nitrophenol, iodoform
Yellow
o-Nitroaniline
Orange
m-Nitroaniline
Golden yellow
p-Nitroaniline
Pale yellow
o-Nitrobenzoic acid
Colorless
Resorcinol
Light pink
p-Cresol
Dark pink
m-Cresol
Dark pink
>-Naphthol
Chacolate
Sulfanilic acid
Grey
Aniline hydrochloride
Colorless but becomes black on keeping
Picric acid
Yellow
Azobenzene
Orange
p-Benzoquinone
Yellow
3.3 ODOR Since a large number of organic compounds possess characteristic odors, it is anticipated that olfaction may disclose the presence of certain groups of substances. Except aromatic carboxylic acids other compounds such as alcohols, esters, aldehydes, amines and ketones possess odor. Care must be exercised in smelling organic compounds as the vapors of a large number of compounds are dangerous. Depending on the experience of the worker it may be possible to relate the unknown to a certain class of compounds, for instance, esters have familiar fruity odor while aromatic hydrocarbons possess characteristic aroma.
3.4 ACID OR BASE CHARACTER Acidic or basic nature of the sample can be easily established by using a litmus or pH paper. A few milligrams of the compound are dissolved in a suitable solvent like water, ethanol or
DETECTION OF ELEMENTS
29
dioxane and tested with litmus paper. A change in color from blue to red indicates that the substance is acidic and red to blue indicates a basic substance. On the other hand, if there is no change then the compound is neutral such as aldehydes, ketones, esters or hydrocarbons. Amines are basic.
3.5 IGNITION TEST A small amount of the sample is placed on a platinum spatula and burnt on a naked flame. This test helps to draw some general inferences. For instance, if the substance burns with a smoky flame then it is considered aromatic but aliphatic if the flame is yellowish. Sulfanilic acid seems to be an exception as it does not burn with a smoky flame. Certain compounds like sugars char and leave a black residue on the spatula and emit a characteristic odor. Organic compounds that do not burn in the ignition test may have a high molecular weight or a high ratio of halogen to hydrogen.
3.6 SOLUBILITY In general, low molecular weight organic compounds containing polar functional groups are soluble in water. Others are soluble in common organic solvents such as ethanol, acetone, benzene, chloroform, etc. The solubility characteristics of a compound may be useful in the classification of the unknown. The quantity of the compound and the solvent employed in the solubility test are critical if reliable information is to be derived. Normally a compound is considered soluble if the solubility of that compound is greater than 3 parts of compound per 100 parts of the solvent at room temperature. In other words, the compound is soluble if it dissolves to the extent of about 30 mg of solid or one drop of the liquid in 1 ml of the solvent. The solvents recommended for use in this test are water, 5% sodium hydroxide, 5% hydrochloric acid and 5% sodium bicarbonate. By checking the solubility of a compound in these reagents, it may be possible to determine whether the unknown has a low molecular weight, neutral compound, an acid, a base or a salt. The following scheme may be useful for classification by means of solubility (p. 30). This chart offers only a guideline of classifying the compounds by means of solubility. It is not essential to test the compounds in all of the solvents, but solvents should be used in the order listed. In case the substance is soluble in water, it should be tested in ether in order to determine if it is a salt. However, if the compound is insoluble in water there is no need to try ether as solvent, rather treated with sodium hydroxide, hydrochloric acid, sodium bicarbonate. If there is a doubt whether or not an appreciable quantity of the substance has dissolved in acid or base, the clear solution should be separated from the rest of the compound and neutralized to see if the original compound separates.
Questions 3.1 What are the inferences drawn from the solubility test? 3.2 Ethyl iodide is polar but unlike such polar compounds as alcohol and acetic acid it is insoluble in water. Explain.
30 LABORATORY MANUAL OF ORGANIC CHEMISTRY
31
DETECTION OF ELEMENTS
3.7 ELEMENTAL ANALYSIS After making the preceding preliminary examinations, the next important class of tests is the detection of elements in the unknown. The elements usually detected are N, S and the halogens (F, Cl, Br, I) whereas C and H are always assumed to be present. The presence of oxygen as a part of the functional group will become apparent later. For the detection of elements the organic substance is first decomposed by fusion with sodium metal to prepare an extract, called the sodium fusion extract. Procedure: Freshly cut a piece of sodium metal about a quarter size of a pea and dry in the
folds of a filter paper (sodium is dangerous, therefore, handle it carefully). Use a sharp knife to cut sodium. Never throw scraps of sodium in water. Place the sodium piece in an ignition tube held with a pair of tongs. Heat the lower part of the tube on a flame until sodium melts. Remove the tube from the flame and rapidly add a small amount (0.2 g of the
solid or 4 drops of the liquid ) of the sample directly over the melted sodium. Again heat the tube to redness, a brisk reaction is observed. Remove the tube from the flame, add another small portion of the unknown sample and heat the tube again till it is red hot. Then immediately immerse the tube in 15 ml of distilled water taken in a china dish, and crush into small pieces with a glass rod. This will hydrolyze sodium and dissolve the ions in water. Boil the mixture for 5 minutes and filter hot to remove the glass splinters. The alkaline filtrate so obtained is usually called the sodium fusion extract. This solution is used in subsequent tests for elemental analysis.
Chemical reactions: C, N
(i) Na (ii) H2 O
+
Na CN
S
Na2
X
Na
+
+
S X
2
X = Cl, Br, I During this process sodium metal combines with the elements present in the sample and converts them into water soluble salts as shown in the above equations.
(a) Tests for nitrogen Take 1 ml of sodium fusion extract in a test tube and add 2 drops of freshly prepared saturated ferrous sulfate solution. A green precipitate should be obtained. In case no such precipitate is obtained, add a few drops of sodium hydroxide solution. At this stage a green precipitate should appear. The green precipitate is due to the formation of Fe(OH) 2 and not due to the presence of nitrogen. Ferrous hydroxide reacts with sodium cyanide to form sodium ferrocyanide. Boil the mixture for 10 sec. and acidify with dil. sulfuric acid, while
32
LABORATORY MANUAL OF ORGANIC CHEMISTRY
shaking till a clear solution is obtained. A Prussian blue color indicates the presence of nitrogen. This is called the Lassaigns test.
Chemical reactions: FeSO4 + 2NaOH Fe(OH)2 + 6 NaCN
3Na 4 Fe(CN) 6 + 2 Fe 2 (SO) 4 3
Fe(OH)2 + Na 2SO4 Na4 Fe(CN)6 + 2NaSO4
Sodium ferrocyanide
Fe4 Fe(CN)6 + 6Na 2SO 4 3
Ferri-ferrocyanide
On boiling the alkaline solution some ferric ions are produced by the oxidation of ferrous ions by air. Both ferrous and ferric hydroxides dissolve on adding dil. sulfuric acid. The ferrocyanide reacts with ferric ions to produce the Prussian blue color of ferriferrocyanide. The alkaline solution should not be acidified by hydrochloric acid because the yellow color due to the ferric chloride formed causes Prussian blue to appear greenish. Ferric chloride, as is usually recommended, should not be added for the same reason.
Questions 3.3 Why should ferrous sulfate solution be fresh and saturated in the test for the detection of nitrogen? 3.4 Would hydrazine hydrochloride give Lassaignes test for nitrogen?
(b) Tests for sulfur The presence of sulfide ion and hence of sulfur in the sodium extract is easily detected since many metal ions (Pb, Ag, etc.) form insoluble sulfides. In a test tube acidify 1 ml of sodium extract with dil. acetic acid. In acid any sulfide ion present is converted to hydrogen sulfide gas. Add 12 drops of lead acetate solution (preferably saturated solution). The appearance of a black precipitate due to the formation of lead sulfide indicates sulfur.
Chemical reactions: Na 2+ S 2− + 2CH3COOH
2CH3COO − Na + + H 2S
(CH3COO)2 Pb + H2S
PbS + 2 CH3COOH
33
DETECTION OF ELEMENTS
Sometimes a brownish precipitate is formed which indicates sulfur containing impurities in the sample. Add 12 drops of freshly prepared solution of sodium nitroprusside to 0.5 ml of the sodium fusion extract in a test tube. A deep red or violet color confirms sulfur.
Chemical reaction:
[
Na 2 + S −2 + Na 2 Fe(CN) 5 NO
]
[
Na 4 Fe(CN) 5 NOS
Sodium nitroprusside
]
(Deep red or violet)
(c) Tests for sulfur and nitrogen present together When both of these elements are present in the unknown, this implies that fusion is incomplete and no sodium cyanide or sodium sulfide is formed but formation of sodium thiocyanate containing both N and S elements takes place. The sodium extract does not respond to individual tests for nitrogen and sulfur. In such a case proceed as follows: Acidify 1 ml of sodium extract with dil. hydrochloric acid and add 12 drops of ferric chloride solution, a blood red color indicates the presence of both sulfur and nitrogen due to the formation of sodium sulfocyanide.
Chemical reactions: C + N + S
Na
NaCNS Sodium thiocyanate
3 NaCNS + FeCl3
Fe (CNS)3 + 3 NaCl Ferric sulfocyanide
(d) Tests for halogens (i) Beilstein test: Make a small loop (23 mm diameter) at one end of a copper wire (10 cm or longer). Insert the other hand of the wire in a cork. Heat the loop to redness in a flame and then cool it. Dip the loop into the unknown and heat it in the nonluminous (blue) flame of the burner appearance of green or blue flame indicates a halogen compound. Try this test, first taking a simple halogen compound such as chlorobenzene. (ii) Silver nitrate test: Acidify 2 ml of the sodium fusion extract with dil. nitric acid and boil. Add several drops of silver nitrate solution. If halogens are present a flocculent white or yellow precipitate which darkens on exposure to light and is soluble in ammonium hydroxide indicates the presence of halogens. The acidification of the sodium fusion extract is necessary before adding silver nitrate solution to prevent the precipitation of silver hydroxide or silver oxide.
34
LABORATORY MANUAL OF ORGANIC CHEMISTRY
Chemical reaction: Na + X + AgNO3
dil. HNO3
AgX + NaNO 3
The above test shows the presence of halogens in the sample. Since all the halogens precipitate in this test as AgX, this determination is incomplete, therefore, the presence of individual halogen has to be made. Fluorine is not detected in this test since silver fluoride is soluble in water. In order to detect the individual halogens proceed as follows. Acidify 2 ml of the sodium extract with dil. nitric acid and boil. Add 45 drops of carbon tetrachloride and 1 ml of fresh chlorine water. Shake the contents vigorously. If the resultant carbon tetrachloride layer is colorless and also a flocculent white precipitate is obtained on the addition of silver nitrate which is soluble in ammonium hydroxide, then it indicates chlorine. A brown color of the carbon tetrachloride layer indicates bromine while a violet color indicates iodine. The advantage in this test is that bromine and iodine have characteristic colors.
Chemical reactions: AgCl + 2 NH3
Ag (NH 3 )2 + Cl − Silver diamine complex
2 NaBr + Cl2 2 NaI + Cl2
2 NaCl + Br2 (Red-orange) 2 NaCl + I2 (Violet)
(e) Detection of more than one halogens If the sample contains more than one halogens then the following procedure may be adopted. This is a sensitive test and thus should be performed carefully. Acidify 2 ml of sodium fusion extract with acetic acid. If the unknown has been shown to contain nitrogen or sulfur then the mixture is boiled to expel hydrogen cyanide or hydrogen sulfide gas and the filtrate is taken. To the filtrate add 34 drops of carbon tetrachloride and several drops of sodium nitrite solution (20%). Appearance of violet color in carbon tetrachloride layer indicates the presence of iodine.
Chemical reaction: 2 NaI + 2 NaNO2 + 4 CH3COOH
I2 + 2 NO + 4CH 3COO Na+ + 2H 2O
Iodine is removed from this solution by a repetition of the above process till the carbon tetrachloride layer becomes colorless. Boil the aqueous layer to remove nitrous oxide.
35
DETECTION OF ELEMENTS
Cool and add a pinch of lead oxide and boil the mixture. If bromine is present a strip of fluorescein paper placed across the mouth of the tube turns pink.
Chemical reaction:
Remove bromine and acidify the aqueous layer with nitric acid and add silver nitrate solution, a heavy white precipitate soluble in ammonium hydroxide indicates chlorine.
Chemical reaction: AgCl + 2 NH4OH
Ag (NH3 )2+ Cl − + H 2O
Alternatively the following procedure may be used if chlorine or one of the other halogens is present. Acidify 2 ml of the sodium extract with dil. nitric acid and add silver nitrate solution. Filter the precipitate and wash twice with distilled water. Transfer the precipitate to a small test tube and shake with 3 ml of ammonium carbonate solution and 2 ml of ammonium hydroxide solution. Filter again and acidify the clear filtrate with dil. nitric acid. Appearance of a flocculent precipitate indicates the presence of chlorine. With another test portion of the sodium extract proceed as in Sec. 2.7(d) to test for bromine or iodine.
(f) Detection of halogens in the presence of nitrogen or sulfur If the sample contains nitrogen or sulfur or both of these elements they should be removed in the form of gaseous compounds. Sodium cyanide if present in sodium fusion extract will form a white precipitate of silver cyanide with silver nitrate which is also soluble in ammonium hydroxide. To 2 ml of the sodium extract add a few drops of dil. nitric acid and boil until the volume is reduced to half. Cyanide or sulfide ions are removed as hydrogen cyanide or hydrogen sulfide gas respectively. Cool the solution and add distilled water followed by silver nitrate solution. A heavy precipitate indicates the presence of halogens.
Chemical reactions: NaCN + HNO3
HCN + NaNO3
Na 2S + 2 HNO 3
H2S + 2 NaNO3
A slight turbidity is not a positive test. To detect the individual halogens proceed as in Sec. 3.7 (d). Fluorine as stated earlier is not detected because silver fluoride is soluble in water. If it is desired to detect fluorine, the following test could be performed.
36
LABORATORY MANUAL OF ORGANIC CHEMISTRY
Take 2 ml of sodium fusion extract and acidify it with glacial acetic acid. Boil the mixture and reduce the volume to one half. With a glass rod, spot this solution on a zirconium - alizarin red S paper. The appearance of a yellow spot is a positive test for the presence of fluorine.
Questions 3.5 Why is the sodium fusion extract acidified before testing for halogens? 3.6 Why should hydrogen cyanide and hydrogen sulfide be expelled before a test is made for halide ion? 3.7 How will you distinguish between a halogen present in the side chain and that in the aromatic nucleus? 3.8 How will you detect chlorine in the presence of iodine? 3.9 Write all the pertinent chemical reactions involved for the detection of chlorine in the presence of nitrogen. 3.10 Why is fluorine not detected in the sodium fusion extract with silver nitrate? Suggest a method for its detection.
Chapter
4
TESTS FOR FUNCTIONAL GROUPS
Detection of a functional group is the next step in the identification of an unknown organic compound. A careful detection of elements is of great help in the establishment of the nature of the functional group. A number of assorted tests for individual groups need to be performed for their identification. In this chapter tests for some selected functional groups will be described.
4.1 ALCOHOLIC GROUP (R–OH) Alcohols may be considered as neutral compounds. They are soluble in water or dioxane. Most alcohols encountered for analysis will be liquid. The following tests can be performed for determining the presence of an OH group in a compound.
(a) Ceric ammonium nitrate test Dissolve 0.5 ml of the unknown compound in 1 ml of water ( or dioxane for water insoluble compounds) and add 1 ml of ceric ammonium nitrate solution. Shake the mixture. A red color is obtained if alcohols are present whereas phenols give a green-brown color.
Chemical reaction:
(b) Xanthate test Add a pellet of potassium hydroxide to 0.5 ml of the unknown liquid sample and warm it till the pellet dissolves. Cool and add a few drops of carbon disulfide and shake. Appearance of a yellow precipitate indicates an alcohol. This test is positive for primary, secondary and tertiary alcohols.
38
LABORATORY MANUAL OF ORGANIC CHEMISTRY
Chemical reactions:
(c) Test with acetyl chloride In a dry test tube, take the unknown sample (0.5 ml of liquid or 500 mg solid ). Add 0.3 ml acetyl chloride dropwise using a pipette. An immediate reaction, indicated by the mixture becoming hot and an ester-like odor is positive indication for an alcohol ( a primary or secondary). Amines and phenols also react, but amines do not give pleasant odors.
(d) Vanadium oxine test In a test tube, place a drop of aqueous ammonium vanadate solution and 1 drop of 8-hydroxyquinoline solution ( oxine) in dil. acetic acid. A green complex of vanadium oxine is formed. Now add 2 ml of alcohol (or a solution in dioxane for water insoluble alcohols ) and shake. A red color is obtained for primary alcohols (ethanol, n-butanol), while secondary alcohols (isopropanol, sec. butanol) yield orange color on keeping, and a light orange color on long standing is obtained in the case of tertiary alcohols ( tert. butanol) test.
(e) Distinction between primary, secondary and tertiary alcohols Once it has been established that an alcoholic group is present, the next logical step is to distinguish between primary, secondary and tertiary alcohols. To achieve this, the unknown is treated with a reagent and the distinction is then made either on the timing of the reaction between the reagent and the compound or on the separation of different products. The Lucas test utilizes the former concept. This test may be used only with water soluble alcohols. Add 34 drops of alcohols to 2 ml of Lucas reagent (anhyd. zinc chloride + conc. hydrochloric acid) in a test tube, shake the mixture and then allow to stand at room temperature. Immediate separation of two phases due to the formation of an insoluble chloride indicates a tertiary alcohol. A cloudy solution is produced in 510 min in the case of secondary alcohol while the solution remains clear for a primary alcohol.
TESTS FOR FUNCTIONAL GROUPS
39
Chemical reactions:
A positive test depends on the fact that alcohol is soluble in the reagent while the alkyl chloride is not. This test fails if zinc chloride is not anhydrous or if the reagent had been sitting on the shelf for a long time. In case of doubt whether the alcohol is tertiary or secondary, conc. hydrochloric acid may be employed. To 1 ml of alcohol in a test tube add 5 ml of conc. hydrochloric acid and shake. A layer of alkyl chloride separates immediately in the case of tertiary alcohol but secondary alcohols react slowly and the solution remains clear (or it may become turbid after sometime).
Chemical reaction:
(f) Chromic acid test A rather rapid test for distinguishing a tertiary from secondary and primary alcohols involves the oxidation with chromic anhydride. Dissolve 1 g of chromic anhydride in 10 ml of conc. sulfuric acid or chromic acid and pour the solution slowly with constant stirring into 30 ml of distilled water. Cool the resultant deep orange solution. This is the oxidizing reagent.
40
LABORATORY MANUAL OF ORGANIC CHEMISTRY
Dissolve 1 drop (10 mg) of the unknown alcohol in 1 ml of pure acetone. Add 1 drop of the above reagent while shaking, the orange color disappears. Primary and secondary alcohols react to give a precipitate that cause the solution to become opaque with a greenish or greenish blue tint. Tertiary alcohols do not react and the test solution remains orange. Any of these changes taking place after two min may be disregarded. For the success of this test the sample should not contain an aldehyde function.
Chemical reactions:
Questions 4.1 What is the basis of the Lucas test? 4.2 Why is it essential to use anhydrous zinc chloride in the Lucas test?
4.2 PHENOLIC GROUP (AR–OH) Phenols are colorless compounds but attain color due to oxidation. Moreover, they are acidic and dissolve in 5% sodium hydroxide solution but not in sodium bicarbonate solution. The tests used to detect phenols are also based on the reactions of the phenolic group. Phenols are generally highly reactive in electrophilic atomatic substitutions. On bromination (bromine water) of phenol, 2,4,6- tribromophenol a white solid compound is obtained.
(a) Ferric chloride test To 1 ml of a dilute solution (50 mg in 1 ml of water or aqueous methanol or ethanol ) of phenol, add 1-2 drops (only) of 5% neutral ferric chloride solution. A colored solution of a complex is produced.
41
TESTS FOR FUNCTIONAL GROUPS
Table 4.1: Observation of Colors in FeCl3 Addition to Phenols Color observed
Compound glass
Blue or bluish violet
Resorcinol, cresols, phloroglucinol, salicylic acid
Green (darkens rapidly)
Catechol
Violet (purple)
Phenol, p-bromophenol, p-chlorophenol
Reddish brown
Pyrogallol
Red violet
m- or p-nitrophenols
Often a white precipitate
=-Naphthol
Green
>-Naphthol
The color produced may not be permanent, therefore, observation should be made at the time of addition. Always use a dilute solution of phenol. This test is negative with m-and p-hydroxybenzoic acids.
Chemical reaction:
The reaction takes place in polar solvents, therefore, a few drops of pyridine are needed
if it is carried out in a non-polar solvent, ( ether, benzene, etc.) . Certain phenols like o-nitrophenol and quinol do not give any color in this test. Ferric complexes are formed in these reactions and polar solvents like methanol is the most suitable medium. Nitrophenols can be expressed as mesomeric structures with a positive charge on the nitrogen atom and competing with ferric ions in their influence on electron pair thus weakening the iron-oxygen bond. Addition of acids destroys the color in this test, p-hydroxybenzoic acid does not give color for this reason. Salicylic acid, on the other hand gives a blue color because it forms a strong complex with ferric chloride.
Question 4.3 Why does o-nitrophenol give no color with FeCl 3 solution?
42
LABORATORY MANUAL OF ORGANIC CHEMISTRY
(b) Liebermann test Place 0.2 g of the unknown in a dry test tube and dissolve in 1 ml of conc. sulfuric acid. Add a few crystals of sodium nitrite. Immediately a blue green or blue violet color is formed. Dilute the contents with water, the color changes to red which turns blue on dilution with sodium hydroxide solution. Color formation is observed due to the production of a salt of indophenol.
Chemical reaction:
Only those phenols possessing a free para position respond to this test. Resorcinol responds to this test.
(c) Phthalein test Heat 0.2 g each of the unknown and phthalic anhydride with only 2 drops of conc. sulfuric acid in a test tube for 1 min. Cool and carefully add the contents to 10% sodium hydroxide solution taken in a beaker. Characteristic colors are obtained. Table 4.2: Colors observed in Phthalein Test Color observed
Likely alcohol
Pink
Phenol
Blue
Catechol
Red solution with green flourescence
Rosorcinol
Deep purple
Hydroquinone
Faint green
=-and >-Naphthols
No color
p-Cresol
43
TESTS FOR FUNCTIONAL GROUPS
Chemical reaction:
Questions 4.4 In the bromination (Br 2 + H 2O) of phenol though hydrogen bromide is evolved but its evolution is not observed why? 4.5 Is bromination of phenol faster in water or carbon tetrachloride?
4.3 CARBONYL GROUP
Tests for the detection of aldehydes and ketones
groups will be discussed under
this section. These are neutral compounds and contain reactive carbonyl group. In most chemical reactions aldehydes are more reactive than ketones. In many cases they undergo similar reactions, for example, addition and reduction. Thus it is necessary at first to
44
LABORATORY MANUAL OF ORGANIC CHEMISTRY
distinguish them from alcohols. One useful method to do this is to treat them with 2,4dinitrophenylhydrazine, whereby a bright orange crystalline solid separates out in the case of carbonyl compounds only, but not alcohols.
The high reactivity of the compounds with this reagent is due to the character of the carbonyl group.
In a test tube take 0.1 g (3 drops if liquid) of the unknown and dissolve in 2 ml of 95% ethanol. Add 23 drops of the 2, 4-dinitrophenylhydrazine solution into the tube and shake. Allow the tube to stand for 15 minutes or till a precipitate is formed. Scratch the sides of the tube if necessary formation of a crystalline yellow or orange-red precipitate indicates an aldehyde or ketone.
Aldehydes are generally more reactive than ketones, the former are identified by oxidizing reagents such as Tollens, Benedict and chromic acid.
(a) Tollens’ test In a test tube place 1 ml of freshly prepared 10% silver nitrate solution. To this add 1 ml of 10% ammonium hydroxide solution shaking it till the precipitate formed just dissolves. This solution contains the silver diamine complex Ag(NH 3)2+ which is a weak oxidizing agent. It is readily reduced to metallic silver. Add a few drops ( 0.2 g) of the unknown along the sides of the tube. A silver mirror is deposited due to the reduction of silver ions to metallic silver in the cold or on warming in a beaker of hot water.
Chemical reaction:
Ketones, ethers and even alcohols do not respond to this test because like aldehydes they cannot be oxidized to carboxylic acids. Aromatic aldehydes respond poorly. =-Hydroxyketones are oxidized, though, to diketons.
TESTS FOR FUNCTIONAL GROUPS
45
(b) Schiff’s test Schiff s reagent consists of an aqueous solution of fuchsine (p-rosaniline hydrochloride) decolorized by passing sulfur dioxide gas. It is a specific test for aldehydes and restoration of the pink color of Schiffs reagent takes place. To 1.5 ml of the reagent (I) add a few drops of the unknown substance. A pink color (II) appears in the presence of an aldehyde in the cold. Do not warm the solution.
Chemical reactions:
The appearance of color is not caused by simple oxidation to fuchsine rather represents a specific reaction of the aldehyde group. Fuchsine leukosulfonic acid (I) reacts with aldehyde and sulfurous acid which on elimination of a molecule of sulfurous acid yields the colored mesomeric cation (II ). The reaction mixture should not be heated otherwise a pink color is obtained even in the absence of an aldehyde. In a strongly acidic solution, formaldehyde yields a blue-violet color. All aliphatic and aromatic aldehydes and p-hydroxybenzaldehyde respond to this test, but salicylaldehyde does not.
46
LABORATORY MANUAL OF ORGANIC CHEMISTRY
(c) Benedict’s solution test This is a modification of Fehlings solution test and consists of alkaline cupric ions complexed with cirrate ions. Place 4 ml of Benedicts reagent in a test tube and add a few drops of the unknown (or a solution of the solid in ethanol or water). Heat the mixture to boiling. A positive test is indicated by the formation of a yellow to red precipitate of cuprous oxide. This test is given only by alphatic aldehydes but the reagent is not capable of oxidizing the aromatic aldehydes such as benzaldehyde. Thus it serves to distinguish between aliphatic and aromatic aldehydes.
Chemical reaction:
(d) Chromic acid test This is another method to distinguish between aldehydes and ketones. This reagent oxidizes primary and secondary alcohols and all aldehydes with a characteristic color change. Dissolve 0.1 g of the substance in 1 ml of good grade acetone in a test tube. To this add one drop of the acidic chromic anhydride reagent and shake the tube. Disappearance of the orange color of the reagent and formation of green or blue green precipitate indicates a positive test for aldehydes. There is no visible color change with tertiary alcohols and ketones.
Chemical reactions:
Ketones respond negatively to the above tests and thus can be distinguished from aldehydes. The following test can be employed for the detection of ketones.
(a) Iodoform test (ketones containing
grouping)
Dissolve 0.1 g of the unknown ketone in 2 ml water (methanol or dioxane for water insoluble
TESTS FOR FUNCTIONAL GROUPS
47
substance). To this add 1 ml of 10% sodium hydroxide solution and iodine-potassium iodide reagent dropwise till a definite dark color of iodine persists. Allow it to stand for several minutes at room temperature. If the color disappears add more reagent till the color persists. Allow to stand for 15 min. A positive test is indicated by the formation of a yellow precipitate of iodoform (m.p. 120 oC) of characteristic odor. If the substance was insoluble in water then at the end of the reaction dilute with 10 ml water.
Chemical reactions: This reaction takes place through the formation of a carbanion, therefore, the hydroxyl ions should always be present in excess.
48
LABORATORY MANUAL OF ORGANIC CHEMISTRY
Aliphatic ketones ( acetone, methyl ethyl ketone, 2-heptanone, methyl propyl ketone, etc.), mixed ketones (acetophenone and its p-substituted derivatives) and alcohols (ethanol, iso-propanol, sec-butanol, 2-octanol, etc.) also respond to this test. Since certain alcohols which can be oxidized to methyl ketones give a positive test in the iodoform reaction this test thus only be carried out if presence of a carbonyl group is confirmed.
(b) m-Dinitrobenzene test This test is also employed preferably for methyl ketones. To a dilute solution of the unknown ketone in ethanol add 1% ethanolic mdinitrobenzene solution and 2 drops of dil. sodium hydroxide solution. Development of a red color is observed. Acetone, methyl ethyl ketone, acetophenone give red color immediately. Benzophenone and benzaldehyde give a light red color in the beginning which deepens on standing. Salicylaldehyde gives a yellow color in the beginning which turns pink on standing. Since m-dinitrobenzene itself gives a pink color with sodium hydroxide solution a sample may be prepared for color comparison.
Questions 4.6 Why are aldehydes more reactive than ketones? 4.7 Why do we not use ethanol as solvent in iodoform test? 4.8 Aldehydes react with neutral potassium permanganate to discharge the purple color and give brown precipitate. Why is this not used as a test for aldehydes? 4.9 A compound gives a positive test with 2, 4-dinitrophenylhydrazine but it does not reduce Tollens reagent. What is the nature of the compound? 4.10 Given are three samples of 3-pentanone, pentanal and 2-pentanone. How would you determine by simple tests which is which? Write chemical reactions. 4.11 Write the product of the reaction:
4.12 How would you distinguish between aliphatic and aromatic aldehydes?
TESTS FOR FUNCTIONAL GROUPS
49
4.4 CARBOXYL GROUP Carboxylic acids do not give characteristic color reactions therefore, for this class of compounds the detection depends on their acidity. This is determined by means of litmus
paper for water soluble acids (lower molecular weight acids) and with sodium bicarbonate for water insoluble acids.
(a) Litmus paper test Dissolve 0.1 g of the unknown in a minimum volume of water. With a glass rod apply a drop on a blue litmus paper. A change to red color indicates the substance to be acidic.
(b) Sodium bicarbonate test Place 0.2 g of the unknown in a test tube and add 1 ml of 5% aqueous sodium bicarbonate solution. Appearance of effervescence indicates the presence of an acid.
Chemical reaction:
This test also differentiates between acids and phenols as the latter are insoluble in sodium bicarbonate solution. However, those phenols which contain electron-withdrawing groups such as 2, 4-dinitrophenol are soluble in sodium bicarbonate. A satisfactory identification of an acid requires the preparation of its appropriate derivative.
Questions 4.13 How would you distinguish between benzoic acid and phenol? 4.14 Would you expect a carboxyl group to form an oxime?
4.5 ESTER GROUP Esters are neutral and many of them possess characteristic fruity smell.
(a) Phenolphthalein test Dissolve two drops of the unknown in 12 ml of ethanol and add two drops of phenolphthalein
50
LABORATORY MANUAL OF ORGANIC CHEMISTRY
indicator and two drops of 0.1 sodium hydroxide solution. If on heating the pink color disappears then an ester is indicated.
(b) Hydroxamic acid test Place 0.1 g of the unknown in a test tube and add 1 ml of hydroxylamine hydrochloride solution in ethanol. Make the solution alkaline with 10% sodium hydroxide solution. Heat the mixture just to boiling. Cool and just acidify the solution with dil. hydrochloric acid. Add 1-2 drops of ferric chloride solution. Development of a red-violet color indicates the presence of an ester. In this test the ester is converted to a hydroxamic acid which then complexes with ferric ions to yield a colored species ferric hydroxymate.
Chemical reactions:
Acid chlorides, amides and anhydrides also respond to this test.
4.6 CARBOHYDRATES Mono- and - disaccharides are colorless solids soluble in water but insoluble in most organic solvents. They do not possess sharp melting points rather decompose on heating. They contain reactive groups which give certain color reactions. A classification into reducing and non-reducing sugars can be affected by the Benedicts reagent. All monosaccharides and many disaccharides are reducing sugars. This is ascribed to the presence of an aldehyde or =-hydroxy keto group in the sugar that can partake in an oxidation-reduction reaction. Disaccharides in which one of the rings is a hemiacetal are reducing sugars, but those in which both rings are in acetal or ketal form are non-reducing sugars. This is based on the fact that they cannot be in equilibrium with the aldehydic or the ketonic form.
TESTS FOR FUNCTIONAL GROUPS
51
(a) Molisch test This is a general test for carbohydrates. Dissolve 0.1 g of the unknown in 1 ml water in a test tube. Add 34 drops of a 10% solution of =-naphthol in ethanol and add 1.5 ml of conc. sulfuric acid along the sides of the tube. A violet or red color is formed at the interface of the two liquids. On shaking, the solution attains a dark violet color.
Glucose and fructose ( monosaccharides), sucrose, lactose and maltose (disaccharides) respond to this test
(b) Charring of carbohydrates If the above test is positive then perform the following test. In a small test tube heat 0.25 g of the carbohydrate with 1 ml of conc. sulfuric acid. Immediate charring takes place, which indicates a carbohydrate.
(c) Benedict’s test To 2 ml of Benedicts reagent, add 0.2 ml of a 2% solution in water of the unknown. Boil the mixture and then allow it to cool. A red precipitate forms with a reducing sugar, while the solution remains clear with a non-reducing sugar.
Chemical reaction:
Identification of individual sugars is established by preparing the osazone (see chapter 6). Certain individual tests may also be employed for each sugar. Glucose Take 2 ml of the aqueous solution of sugar in a test tube add 50 mg of lead acetate and heat to boiling. Add 5 ml of dil. ammonium hydroxide and boil the mixture again for 1 minrose pink color appears. Fructose To 2 ml of the aqueous solution of sugar in a test tube add an equal volume of conc. hydrochloric acid and 10 mg of resorcinol warm the tube in a beaker of boiling water for 2 mina deep red color appears followed by a precipitate.
52
LABORATORY MANUAL OF ORGANIC CHEMISTRY
Galactose Place 0.5 g of the substance in a dry test tube and add 1.5 ml of 50% nitric acid. Allow the tube to stand in a beaker of boiling water until red fumes evolve. Then keep the tube for 15 min in another beaker containing water at 70oCa white precipitate results. Sucrose Sucrose does not reduce Fehlings solution. On treatment with conc. sulfuric acid, it gets charred even in cold. Sucrose also responds to color tests. Dissolve 0.5 g of the substance in 2 ml of distilled water. To this add 0.1 g of resorcinol and 1.5 ml conc. hydrochloric acid. Boil the mixture for 2 mina deep wine red color appears.
Questions 4.15 What is the color due to in the Molisch test for carbohydrates? 4.16 How will you distinguish between reducing and non-reducing sugars? 4.17 How will you distinguish between starch and glucose?
4.7 NITRO GROUP Presence of a nitro group is usually indicated by lengthy reduction or oxidation reactions.
(a) Reduction to hydroxylamine compound Dissolve 0.1 g of the unknown in 2 ml ethanol and add 5 drops of calcium chloride solution. Add a pinch of zinc dust and boil the contents for 5 min. Filter the solution is a test tube containing 1 ml of Tollens reagent. A grey or black precipitate (Ag) indicates the presence of a nitro group. Instead zinc and acetic acid may be used for the reduction of the nitro group. In this test the nitro group is partially reduced to hydroxylamine which is itself a reducing agent and gives a positive Tollens test.
Chemical reactions:
This test is applicable if the original unknown gives a negative Tollens test.
TESTS FOR FUNCTIONAL GROUPS
53
(b) Ferrous hydroxide test Place about 20 mg of the unknown in a small test tube and mix with 1.5 ml of freshly prepared 5% solution of ferrous ammonium sulfate. Add 1 drop of 6 N sulfuric acid followed by 1 ml of 2N potassium hydroxide solution in methanol. Stopper the tube quickly and shake vigorouslyred-brown precipitate is obtained.
Chemical reaction:
Question 4.18 Is the evaluative test for the nitro group applicable to p-nitrobenzaldehyde? Explain.
4.8 AMINO GROUP (–NH2) Amines are basic substances insoluble in water but soluble in mineral acids.
(a) Diazotisation and coupling Dissolve 50 mg of the unknown amine in 2 ml of 2N hydrochloric acid in a test tube. Cool the solution to 5 oC in an ice-bath. In a second test tube cool 50 mg of >-naphthol in 2 ml of 10% sodium hydroxide solution. When the solutions are cooled add sodium nitrite solution to the amine with shaking, followed by the addition of >-naphthol solution. Formation of an orange to red dye is indicative of a primary aromatic amine.
Chemical reaction:
(b) Carbylamine test Place a small amount of the amine in a test tube and dissolve in alcoholic sodium hydroxide solution. Add a few drops of chloroform and warm the mixture gently. A foul odor of isonitrile (carbylamine ) is produced.
54
LABORATORY MANUAL OF ORGANIC CHEMISTRY
Chemical reaction:
This reaction should be performed in the fume chamber. Both aliphatic and aromatic primary amines respond to this test. This test is negative both for secondary and tertiary amines. Before pouring into the sink, the mixture should be acidified with dil. hydrochloric acid. This would convert the isonitrile into the corresponding hydrochloride of the amine. A distinction between a primary aliphatic and aromatic primary amines can be made by the coupling test (part a). An additional test for primary aliphatic amines may be performed.
Add 12 drops of the substance (0.1 g for solid) in a test tube. Add 3 ml water followed by 1 ml acetone. Shake to mix. Add 2 drops of 1% aqueous solution of sodium nitropruside. A red-violet color appears. As in the case of alcohols it is also essential to distinguish between primary, secondary and tertiary amines. This can be achieved by the Hinsberg test.
(c) The Hinsberg test In a test tube add three drops ( or 0.1 g) of the unknown amine, 0.2 g of p-toluensulfonyl chloride and 5 ml of 10% sodium hydroxide solution. Shake the tube for 5 min. If no reaction appears to occur, heat the reaction mixture on a steam-bath for 1 min and cool in ice. On cooling, if no solid separates out then the substance is probably a tartiary amine. If a precipitate appears in the alkaline medium add 5 ml of water and shake. If the precipitate does not dissolve it indicates a secondary amine. If the solution is clear, acidify with dil. hydrochloric acid. Appearance of a precipitate indicates a primary amine.
Chemical reaction: Primary amine
The monosubstituted sulfonamide is soluble in sodium hydroxide solution. A precipitate appears on adding hydrochloric acid.
TESTS FOR FUNCTIONAL GROUPS
55
Secondary amine
The disubstituted sulfonamide is insoluble in sodium hydroxide solution. Tertiary amine
The presence of a secondary amine as indicated by the Hinsberg test can be confirmed as follows: Dissolve 0.1 g of NiCl2 . 6H2O in 20 ml of water and add sufficient carbon disulfide until a small globule remains undissolved after the mixture has been shaken vigorously. To 1 ml of this reagent add 1 ml of conc. ammonium hydroxide followed by a solution of 0.1 g of the unknown in 5 ml of water, to which 2 drops of conc. hydrochloric acid have been added, if necessary to complete dissolution of the amine. Shake a precipitate is formed.
Chemical reaction:
Questions 4.19 How will you distinguish between a primary and secondary amine? 4.20 2, 4-Dinitroaniline does not form a salt with 20% hydrochloric acid. Suggest a reason. 4.21 Why are benzamides of primary amines insoluble in aqueous alkali while the corresponding sulfonamides are soluble? 4.22 Why do tertiary amines not react in the Hinsberg test? 4.23 Write the coupling reactions of benzene diazonium chloride with: (a)>-naphthol (b) Phenol 4.24 Do aromatic primary amines undergo coupling reactions? 4.25 Do aliphatic amines give diazotisation and coupling test? 4.26 During diazotisation why the mineral acid should be used in excess?
56
LABORATORY MANUAL OF ORGANIC CHEMISTRY
4.9 AMIDE GROUP (a) Ammonia evolution test A primary amide can be hydrolyzed to carboxylic acid salt in aqueous sodium hydroxide. In a boiling tube take 0.2 g of the unknown and add 1-2 ml of 10% aqueous sodium hydroxide solution. Boil the contents. Evolution of ammonia gas and a blue color of the red litmus paper indicates the presence of an amide group.
Chemical reactions:
This test fails if hydrogen at the nitrogen atom is replaced by an alkyl or aryl group, then an amine is produced.
(b) Hydroxamic acid test Boil approximately 0.1 g of the unknown with 2 ml of 1N hydroxylamine hydrochloride and 2 ml of 1N potassium hydroxide solution for 3-4 min in a boiling tube. Cool and add a few drops of ferric chloride. A red coloration is observed due to the formation of ferric hydroxymate.
Chemical reactions:
A nitrile can also be hydrolyzed to a carboxylic acid salt similar to a primary amide.
57
TESTS FOR FUNCTIONAL GROUPS
Nitriles are slowly hydrolyzed than amides. They can be rather easily hydrolyzed in conc. sulfuric acid.
A nitrile group also undergoes the hydroxamic acid test to form the following red colored species of ferric hydroxymate.
4.10 ANILIDE GROUP
An anilide is formed by substituting a methyl or an aryl group at the nitrogen atom of an amide. Most of the tests for this functional group, usually involve its hydrolysis to an amine and then performing a test or the resulting amino substance.
(a) Diazotisation and coupling test
This test is applicable to acetanilide
and benzanilide
, i.e. those which yield a primary aromatic amine on hydrolysis.
Note it should be performed only in the absence of an aromatic primary amino group.
58
LABORATORY MANUAL OF ORGANIC CHEMISTRY
Place 0.2 g of the compound in a boiling tube. Add 56 ml of 75% sulfuric acid to it and boil the contents for 5 minutes. Dilute it with 3 ml distilled water and filter. Cool the filtrate in ice to 0 5oC. In the cold solution add 2 ml of 10% sodium nitrite solution. To this mixture add a precooled 50 mg solution of >-naphthol in 2 ml of 10% sodium hydroxide. solution. Formation of an orange to red dye indicates an anilide group.
4.11 HYDROCARBONS Hydrocarbons are neutral compounds and do not contain any functional group. Aromatic hydrocarbons possess characteristic odor and burn with a smoky flame. These are insoluble in water but dissolve in many organic solvents. The following two color tests may be applied for their identification. The colors abtained are usually intense. A light yellow color is inconclusive or negative.
(a) Formalin test It is a sensitive test for aromatic hydrocarbons and colored resinous substances are formed. To a mixture of 2 drops of formalin and 2 ml of conc. sulfuric acid add, 2 drops of the unknown solution in 2 ml carbon tetrachloride. Note the appearance of color (Table 4.3). Table 4.3: Colored Reactions of Aromatic Reactions Class of Compound
Color
Benzene (b.p. 110oC) and monoalkylated derivatives
Dark red color (with some black precipitate)
o-Xylene (b.p. 144o C)
Dark brown precipitate
m-Xylene (b.p. 139oC) p-Xylene (b.p. 138°C)
Violet color (with black precipitate) Same as m-xylene
Diphenyl (m.p. 69oC) Naphthalene (m.p. 80oC)
Dark red color (with black precipitate) Same as for diphenyl
Anthracene (m.p. 216oC)
Dark yellow color (with black precipitate)
59
TESTS FOR FUNCTIONAL GROUPS
(b) Aluminum chloride-chloroform test Dissolve 0.1 g (or 3 drops of liquid ) of the unknown in 1 ml chloroform in a clean dry test tube. Shake the tube vigorously. Add a pinch of anhydrous aluminum chloride with a spatula along the wet sides of the tube. The following characteristic color develop (Table 4.4) Table 4.4: Color Development in the AlCl 3 – CHCl3 Test Class of compound
Color
Benzene
AlCl3 crystals attain a yellow color but soon turn dark orange. The CHCl3 layer is colorless.
Toluene
AlCl3 crystals turn orange
o-Xylene
Orange color, chloroform layer initially colorless but turns yellow on keeping.
m-Xylene
Orange color, chloroform layer colorless.
p-Xylene
Dark red color, chloroform layer colorless.
Diphenyl
Purple color, chloroform layer colorless.
Naphthalene
Green color in the beginning turns blue on keeping.
Phenanthrene
Purple color
Anthracene
Light yellow to green color, chloroform layer colorless.
A Friedel-Crafts reaction probably takes place to form colored derivatives. This test should be performed on aromatic hydrocarbons that have been shown insoluble in conc. sulfuric acid.
4.12 UNSATURATION The presence of a
bond can be ascertained by the following
tests.
(a) Addition of bromine Dissolve 50 mg (or 2 drops) of the unknown in 1 ml of dichloromethane or acetic acid. To this add dropwise a 2% solution of bromine also in carbon tetrachloride. Decolorization of the brown color due to the formation of an addition compound is a positive test for unsaturation.
60
LABORATORY MANUAL OF ORGANIC CHEMISTRY
Chemical reaction:
(b) Baeyer’s test Dissolve 50 mg (or 2 drops) of the unknown compound in acetone or water. Dropwise add a
2% aqueous solution of potassium permanganate (23 drops) and shake. The disappearance of purple color of potassium permanganate and appearance of a sparingly soluble brown manganese dioxide is a positive test for unsaturation.
Chemical reaction:
This test may sometimes lead to wrong conclusions because certain other compounds such as aldehydes, phenols, arylamines, primary and secondary alcohols also decolorize potassium permanganate solution. Therefore, it should be carried out judiciously. This test is thus more general and less specific than the addition of bromine.
Questions 4.27 How will you differentiate between cyclohexene and benzene? 4.28 Name an aromatic compound which reacts readily with bromine both by addition and substitution. 4.29 What is Baeyers reagent? 4.30 How will you distinguish between propene and propyne?
4.13 CARBONIC ACID DERIVATIVES Carbonic acid CO(OH)2 on replacement of the oxygen atom or both the OH groups by groups such as N, S or halogens forms important compounds. However, individual tests for only two of these, i.e., urea and thiourea will be discussed here.
TESTS FOR FUNCTIONAL GROUPS
61
A. Urea (NH2CONH2), m.p. 132oC Urea is a diamide of carbonic acid (H 2CO3). An aqueous solution of urea is virtually neutral.
(a) Biuret test Gently heat 0.2 g of the unknown in a dry test tube until the melted substance just solidifies. Ammonia gas is evolved and white solid remains which is known as biuret. Dissolve the residue in 1 ml of warm water and 1 ml of 10% sodium hydroxide solution. Cool and add 12 drops of very dilute copper sulfate solution. A violet or purple color is a positive test for urea.
Chemical reactions:
(b) Urea nitrate Dissolve 50 mg of urea in 1.5 ml water. Warm, if necessary. Add 1.5 ml of conc. nitric acid and cool. Filter and wash the solid carefully with cold water and dry, m.p. 163 oC.
Thiourea also evolves ammonia gas on heating alone or in the presence of base similar to urea.
(a) Potassium ferrocyanide test In a test tube place 25 mg of the substance and dissolve in 2 ml of dil. acetic acid. Heat until the solution is complete. To the hot solution add 2 ml of potassium ferrocyanide solution, a green color changing to blue is produced. The blue color is obtained immediately if the mixture is heated.
62
LABORATORY MANUAL OF ORGANIC CHEMISTRY
(b) Ferric chloride test In a test tube heat 25 mg of the substance on a flame until the solid melts. Cool and dissolve the solid in 2 ml water. Add 2 ml of ferric chloride solution. Fill the test tube with water and invert, a deep red solution is obtained.
Questions 4.31 What happens when urea is (a)
reacted with hydrazine.
(b)
heated alone.
(c)
refluxed with a base.
4.32 What happens when urea is heated with alkaline KMnO 4 solution?
Chapter
5
TESTS FOR COMMON ORGANIC COMPOUNDS
A large number of organic compounds contain more than one functional groups, and the properties of one group may be masked by the other. Therefore, to classify the compound correctly, additional tests need to be performed. The final decision, however, would rest on
the preparation and identification of its derivative (Chapter 6). In some cases such tests to be described in this chapter may even assist in identifying the compound itself.
5.1 ALCOHOLS AND PHENOLS b.p. (°C) 65
Methyl alcohol CH3OH
It is a colorless liquid miscible with water in all proportions and has a characteristic smell. (a) Place 2 drops of the compound in a test tube. Bend a copper wire into a compact form. Heat it to red hot and drop into the tube a pungent odor of formaldehyde. (b) 3, 5-Dinitrobenzoate, m.p. 107°C.
78
Ethyl alcohol CH3CH2OH
It is a colorless liquid, miscible with water and has a characteristic spirit like odor. (a) It responds to iodoform test. (b) It gives a characteristic strong smell of acetaldehyde on heating with copper wire. (c) 3, 5-Dinitrobenzoate, m.p. 92°C.
64
82
LABORATORY MANUAL OF ORGANIC CHEMISTRY
Isopropyl alcohol (CH3)2CHOH
It is a colorless liquid and miscible with water. (a) In a test tube place 2 ml of iodine solution and add 1 drop of alcohol. Now add dil. sodium hydroxide solution dropwise till the deep brown color of iodine turns pale yellow. Shake the tubea yellow precipitate of iodoform appears. (b) Fit up an apparatus consisting of a 50 ml distilling flask and a water condenser. Place 1 ml of the compound into the flask and 20 ml of the dichromate solution. Distil the mixture until 5 ml of the distillate has been collected. This distillate contains acetone; make a 2, 4-dinitrophenylhydrazone, m.p. 125°C.
83
tert-Butyl alcohol (CH3)3COH
Take 1 ml of the aqueous solution and 4 ml of conc. hydrochloride acid in a test tube and shake. There is an immediate formation of an insoluble liquid, alkyl chloride which forms an oily layer.
96
Allyl alcohol CH2=CHCH2OH
It possesses an irritating odor and is soluble in water. (a) Add 2 drops of the aqueous solution of the alcohol in 4 ml of bromine water. There is an immediate disappearance of bromine color due to the formation of a dibromide, b.p. 212°C. (b) On oxidation with potassium dichromate and dil. sulfuric acid, allyl alcohol forms acrolein which has a more irritating odor than the alcohol itself.
97
n-Propyl alcohol CH3CH2CH2OH
It is a colorless liquid, miscible with water. It is oxidized by hot potassium dichromate and dil. sulfuric acid to propionaldehyde. This can be tested by the addition of Schiffs reagent to the distillatea deep violet-red color is obtained.
100 sec-Butyl alcohol It is soluble in water. (a) Add 1 drop of the aqueous solution of alcohol to 2 ml of iodine solution followed by the addition of dil. sodium hydroxide solution dropwise, till the deep brown color of iodine changes to pale yellow. Shakeyellow precipitate of iodoform appears. (b) On boiling with conc. hydrochloric acid it yields sec butyl chloride, b.p. 67°C.
108 Isobutyl alcohol It is a colorless liquid and is soluble in water.
TESTS FOR COMMON ORGANIC COMPOUNDS
65
On boiling with hot potassium dichromate and dil. sulfuric acid, isobutyraldehyde distils over. This can be tested by the Schiffs reagent.
117 n-Butyl alcohol CH3CH2CH2CH2OH On boiling with hot potassium dichromate and dil. sulfuric acid, butyraldehyde is formed which can be confirmed by testing with the Schiffs reagent.
160 Cyclohexanol It is soluble in water. (a) On boiling with potassium dichromate and dil. sulfuric acid, it forms cyclohexanone, b.p. 115°C, but on oxidation with hot conc. nitric acid, adipic acid m.p. 149°C is obtained. (b) Distillation of cyclohexanol in the presence of catalytic amount of phosphoric acid or conc. sulfuric acid yields cyclohexene, b.p. 83°C.
176 o-Chlorophenol It is slightly soluble in water but completely so in alcohol and ether. It gives violet color with ferric chloride solution.
196 o-Bromophenol It gives violet color with ferric chloride solution. On treatment with bromine water it yields tribromophenol, m.p. 95°C.
197 Ethylene glycol It is a colorless and pleasant odor liquid insoluble in water, soluble in ether. =-Naphthyl carbamate, m.p. 53°C.
197 Linalool
It possesses a pleasant odor and is soluble in water.
66
LABORATORY MANUAL OF ORGANIC CHEMISTRY
(a) Add 2 drops of the aqueous solution of the alcohol to 3 ml of bromine water in a test tube. The bromine color immediately disappears. This shows the presence of unsaturation in linalool. (b) Acetate, b.p. 103°C/30 mm. (c) =-Naphthyl carbamate, m.p. 53°C.
202 m-Cresol It is denser than water and is only slightly soluble in it. (a) With ferric chloride solution it gives a blue-violet color. (b) Benzoate, m.p. 54°C and picrate, m.p. 88°C.
205 Benzyl alcohol C6H5CH2OH It has a faint aromatic ordor. (a) To 2 ml of dil. nitric acid in a test tube and add 1 drop of the alcohol and allow the test tube to stand in a beaker of boiling water. A pale yellow emulsion and a strong odor of bitter almonds develops due to the formation of benzaldehyde. (b) In a 100 ml round-bottomed flask take, 0.25 g of potassium permanganate and dissolve in 2.5 ml of water. Heat the solution to boiling and add 0.5 g of benzyl alcohol. Then allow the flask to stand at room temperature with frequent shaking till the purple color disappears. Filter and acidify the filtrate with conc. hydrochloric acid, benzoic acid is formed, filter wash with cold water and dry. m.p. 121°C.
214 m-Chlorophenol On reaction with 50% nitric acid in the cold it yields a 4-nitro derivative, m.p. 133°C.
220 =-Phenylethyl alcohol It is soluble in water and the aqueous solution has the odor of rose oil. (a) On oxidation (described above under benzyl alcohol ) it yields benzoic acid, m.p. 121°C. (b) Acid phthalate, m.p. 188°C.
TESTS FOR COMMON ORGANIC COMPOUNDS
67
222 Citronellol
(a) It possesses a pleasant odor and unsaturation which can be detected by bromine water. (b) Acetate, b.p. 120°C/15 mm.
230 Geraniol
It possesses the odor of roses as well as unsaturation. (a) With bromine it forms a tetrabromo derivative, m.p. 70°C. (b) Acetate, b.p. 244°C.
m.p. (°C)
30
o-Cresol
It has a carbolic acid odor and gives violet color with ferric chloride solution. (a) In a dry test tube place a few milligrams of phthalic anhydride and twice the amount of the compound. Add 2 drops of conc. sulfuric acid and heat the mixture on a flame gently till the mixture attains a red-brown color. Cool and add a few drops of water to the mixture followed by dil. sodium hydroxide solution dropwise till the solution is alkaline. Appearance of red color indicates o-cresol or phenol. (b) To 2 ml of conc. ammonium hydroxide solution add a pinch of the compound. If the compound is undissolved then it shows o-cresol, but if a clear solution is obtained then it is phenol.
33
Cinnamyl alcohol (a) To 1 drop of bromine solution in 2 ml carbon tetrachloride add 2 drops of the
68
LABORATORY MANUAL OF ORGANIC CHEMISTRY
compound and shake. The brown color of bromine disappears forming a dibromide (m.p. 74°C). (b) On oxidation with potassium permaganate it yields benzoic acid, m.p. 121°C.
35
Terpineol
It also contains unsaturation and decolorizes bromine color. (a) On treatment with gaseous hydrochloric acid it forms a dipentene dihydrochloride, m.p. 50°C. (b) Acetate, m.p. 195°C.
36
p-Cresol
It is a colorless liquid but becomes colored on keeping. It is soluble in organic solvents. Like the ortho isomer it has a carbolic acid odor as well. (a) It yields blue color with ferric chloride solution. (b) With excess bromine it forms a tetrabromo derivative, m.p. 109°C.
42
Phenol
It forms an emulsion with water. (a) With ferric chloride solution it gives a violet color. (b) It can be confirmed by the test listed under o-cresol. (c) With bromine water it is readily brominated to yield a tribromo derivative, m.p. 93°C.
43
p-Chlorophenol
It is insoluble in water but soluble in ethyl alcohol. (a) It gives violet color with ferric chloride solution. (b) On reaction with conc. nitric acid it yields a 2, 6-dinitro derivative, m.p. 81°C.
TESTS FOR COMMON ORGANIC COMPOUNDS
45
69
o-Nitrophenol
It is yellow in color and has a tarry odor. It is readily soluble in hot water and most organic solvents. It gives no color with ferric chloride solution. (a) Dissolve 25 mg of the compound in water and add 2 ml of dil. sodium hydroxide solution. Shakedeep red color. (b) With conc. nitric acid and sulfuric acid it is nitrated to give yields picric acid, m.p. 114°C.
64
p-Bromophenol
With bromine water it yields tribromophenol, m.p. 95°C.
69
Diphenyl carbinol (Benzhydrol)
Colorless crystalline solid, insoluble in water (a)
94
3, 5-Dinitrobenzoate, m.p. 142°C.
=-Naphthol
It gives no color with neutral ferric chloride solution but a white precipitate. (a) Place 0.5 ml of the compound in a test tube. Add 2 ml of dil. sodium hydroxide solution, and 1 drop of chloroform. Warm the mixturea blue color is obtained with both =- and >-napththols. Take a mixture of 10 ml of iodine solution and dil. sodium hydroxide solution in a test tube and add 50 mg of the compound. A violet precipitate appears which darkens rapidly=-naphthol. If there is no change in the solution>-naphthol. (b) Warm a pinch of the substance with dil. sodium hydroxide solution, carbon tetrachloride and some copper powder in a test tubea blue color appears.
70
97
LABORATORY MANUAL OF ORGANIC CHEMISTRY
m-Nitrophenol
It is pale yellow in color but odorless and is soluble in hot water and most organic solvents. (a) Dissolve 25 mg of the compound in hot water, add 2 ml dil. sodium hydroxide solutionorange-red color. (b) Dissolve 25 mg of the compound in 5 ml of water and heat to boiling. Cool and add a few drops of ferric chloride solution violet-red color.
105 Catechol It is readily soluble in water and yields green color with ferric chloride solution. (a) To the aqueous solution of the alcohol in a test tube, add an equal volume of lead acetate solution a white precipitate appears immediately. (b) With bromine it yields a tetrabromo derivative, m.p. 192°C.
110 Resorcinol It is readily soluble in water and gives blue-violet color with ferric chloride solution. (a) In a dry test tube place 25 mg of phthalic anhydride, 50 mg of the compound and 2 drops of conc. sulfuric acid. Heat gently on a flame until the mixture is redbrown in color. Cool and add a few drops of water followed by dil. sodium hydroxide solution till the solution is alkaline. Place one drop of this solution in a second tube and fill it up with water a yellow green fluorescence. (b) Warm 50 mg of the alcohol with dil. sodium hydroxide solution and chloroform red color with green fluorescence.
114 p-Nitrophenol It is pale yellow in color but odorless. It is soluble in hot water, alcohol and ether. (a) To 25 mg of the compound in a test tube add 1 ml of water followed by 2 ml of dil. sodium hydroxide solution an intense yellow color. (b) Dissolve 25 mg of the compound in 5 ml of water and add 2 drops of ferric chloride solution violet red color.
TESTS FOR COMMON ORGANIC COMPOUNDS
71
122 Picric acid
It is light yellow in color and soluble in hot water, alcohol and benzene. (a) To 5 ml of dil. sodium hydroxide solution, add 25 ml of the compound and heat just to boiling. To the intense yellow colored solution obtained, add a drop of ammonium sulfide solution a deep red color.
123 >-Naphthol It gives green color with neutral ferric chloride solution. (a) Perform the test as in =-naphthol. (b) Dissolve a pinch of the substance in a test tube in conc. sodium hydroxide solution and chloroform. Warm the mixture a light bluish green color with a heavy precipitate. =-Naphthol gives a dark blue color.
133 Pyrogallol
It is a white crystalline substance which turns black on exposure to air. It is readily soluble in water. (a) To 2 ml of the aqueous solution add a pinch of ferrous sulfate and shake a blueviolet color. (b) Triacetate, m.p. 161°C.
165 Triphenylmethanol (C6H5)3COH The alcohol is insoluble in water. (a) Add 0.2 g of the substance in 2 ml of conc. sulfuric acid and shake intense yellow color. (b) Acitate, m.p. 88°C.
166 D-Mannitol CH2OH(CHOH)4CH2OH It is a colorless solid, soluble in water but insoluble in ether and alcohol.
72
LABORATORY MANUAL OF ORGANIC CHEMISTRY
(a) To 1 ml of copper sulfate solution in a test tube, add ammonium hydroxide solution till the blue color initially obtained becomes colorless. To this ammoniacal copper sulfate solution add 0.1 g of the substance and shake blue precipitate is formed. (b) Hexaacetate, m.p. 119°C. (c) Hexabenzoate, m.p. 124°C.
170 Quinol It is soluble in water and gives a transient blue color with ferric chloride solution. (a) Dissolve 50 mg of the compound in 2 ml dil. sulfuric acid in a test tube by warming. Cool the solution and add 25 mg of potassium dichromate immediate precipitate of quinhydrone consisting of green needles. (b) Diacetate, m.p. 123°C.
174 o- Aminophenol It is sparingly soluble in cold water but readily so in ether. (a) It gives a dark brown precipitate with ferric chloride solution. (b) With silver nitrate solution, a yellow brown color is obtained slowly but rapidly on warming.
186 p-Aminophenol It is soluble in cold water but sparingly soluble in ether. It gives a purple color with ferric chloride solution.
218 Phloroglucinol
It is soluble in water and gives a transient blue color with ferric chloride solution. (a) Triacetate, m.p. 105°C.
TESTS FOR COMMON ORGANIC COMPOUNDS
73
5.2 CARBOXYLIC ACIDS b.p. (°C) 100 Formic acid HCOOH It is micible with water and has a penetrating odor. (a) To 2 ml of the neutral aqueous solution of the acid add an equal volume of ferric chloride solutiona wine red-color. (b) In a test tube place 2 ml of neutral solution of the acid and 1 ml of mercuric chloride solution. Boil for 30 sec appearance of a white precipitate due to the formation of mercurous chloride due to reduction.
118 Acetic acid CH3COOH It is miscible with water and responds similarly to test (a) for formic acid. In a porcelain dish take 0.5 g of the acid and 2 g of phosphorus pentachloride. Grind the mixture until it becomes liquid. To this crude acid chloride add 10 ml of conc. ammonium hydroxide. When the vigorous reaction has ceased, stir, cool and filter the amide. Wash it with cold water and dry acetamide, m.p. 82°C.
140 Propionic acid CH3CH2COOH It is miscible with water and also gives the color test listed in (a) for formic acid. Amid, m.p. 79°C.
155 Isobutyric acid (CH3)2CHCOOH It is a colorless liquid with unpleasant smell. It is sparingly soluble in water but soluble in alcohol and ether. (a) On heating with conc. sulfuric acid, carbon monoxide and sulfur dioxide are evolved. (b) Amide, m.p. 129°C. (c) Hydrazide, m.p. 104 °C.
162 n-Butyric acid CH3CH2CH2COOH It is miscible with water and has the odor of rancid butter. Amide, m.p. 129°C.
m.p. (°C) 72
Crotonic acid CH3CH=CHCOOH
It is soluble in water. To 2 ml of bromine water add 1 ml of the aqueous solution of the acid bromine color is decolorized.
74
76
LABORATORY MANUAL OF ORGANIC CHEMISTRY
Phenylacetic acid
It is soluble in hot water. It is oxidized by potassium dichromate and sulfuric acid to benzoic acid (m.p. 121°C).
100 Citric acid It is soluble in water and loses water of crystallization at 130°C, forming anhydrous acid (m.p. 153°C). (a) To 3 ml of the neutral solution add 1 ml of calcium chloride solution and heat the mixture to boiling for 1-2 min a heavy white precipitate of calcium citrate. (b) To 1 ml of the neutral solution add 2 drops of sodium introprusside solution a red color which changes to violet on adding acetic acid. (c) Amide, m.p. 215°C
101 Oxalic acid It is soluble in water. (a) Place 50 mg of the acid in a test tube and add 5 drops of conc. sulfuric acid. Gently warm the tube on the flame and turn the mouth of the tube periodically to the flame carbon monoxide burns with a blue flame. (b) In a test tube place one crystal of oxalic acid and a small amount of diphenylamine and heat the mixture with twice the amount of zinc chloride. The mixture first melts and then turns blue due to the formation of a triphenylmethane dye. (c) Dimethyl oxalate, m.p. 54°C.
105 o-Toluic acid It is sparingly soluble in water. In a mortar grind 20 mg of the acid with an equal amount of soda lime. Pour the mixture in an ignition tube and heat smell of toluene.
TESTS FOR COMMON ORGANIC COMPOUNDS
75
110 m-Toluic acid It is sparingly soluble in water. (a) It also yields toluene on heating with soda lime. (b) Amide, m.p. 94°C.
118 Mandelic acid It is soluble in water. To 50 mg of the compound in a test tube add equal volumes of aqueous potassium permanganate and sulfuric acid and heat odor of benzaldehyde.
121 Benzoic acid It is soluble in hot water, but sparingly soluble in cold water. On heating with soda lime it yields benzene.
133 Cinnamic acid It is sparingly soluble in water. (a) On oxidation with potassium permanganate it forms benzoic acid, (m.p. 121.2°C). (b) Amide, m.p. 146°C.
135 Acetylsalicylic acid (Aspirin) It is sparingly soluble in water and gives no color with ferric chloride solution. To 50 mg of the substance in a dry test tube add 10 drops each of methyl alcohol and conc. sulfuric acid and heat gently. Cool and pour into 5 ml of water taken in a beaker smell of methyl salicylate ( oil of wintergreen). (a) Amide, m.p. 138°C.
76
LABORATORY MANUAL OF ORGANIC CHEMISTRY
137 o-Chlorobenzoic acid It is soluble in hot water. (a) Amide, m.p. 106°C.
139 o-Nitrobenzoic acid It is a colorless solid and soluble in boiling water. (a) Grind 20 mg of the acid and an equal amount of soda lime in a mortar. Introduce the mixture in an ignition tube. Heat smell of nitrobenzene (bitter almonds).
(b) Amide, m.p.142°C.
141 m-Nitrobenzoic acid It is pale yellow in color and only slightly soluble in water. Gives the test (a) as in o-nitrobenzoic acid.
144 Anthranilic acid It is soluble in water and in alcohol with a blue fluorescence. (a) With bromine it yields a 2,6-dibromo derivative, m.p. 227°C (b) To 100 mg of the compound in a test tube add 3 ml of acetone, shake to dissolve the solid, then add 1 ml of acetic anhydride. Allow to stand for 2 min then add 5 ml of aqueous sodium hydroxide solution. Sodium hydroxide solution is added to partially neutralize the excess acid, the solution should remain acidic at this stage. Cool and shake. Filter the solid and wash with cold water the acetyl derivative, m.p. 185°C.
150 o-Bromobenzoic acid It is soluble in hot water. Amide, m.p. 155°C.
TESTS FOR COMMON ORGANIC COMPOUNDS
77
152 Adipic acid It is soluble in water (a) Place 20 mg of the compound in a test tube and add twice the amount of resorcinol and 2 drops of conc. sulfuric acid. Heat the mixture gently till it turns reddishbrown. Cool and add several drops of water and then dil. sodium hydroxide solution till alkaline. Take 1 ml of this solution into another test tube and fill it up with water violet-red color. (b) Amide, m.p. 220°C.
155 m-Bromobenzoic acid It is sparingly soluble in water. (a) On fusion with potassium hydroxide this acid gives m-hydroxybenzoic acid (m.p. 200°C). (b) Amide, m.p. 155°C.
158 Salicylic acid It is not soluble in cold water. (a) Add 20 mg of the acid to 2 ml of water and shake. Add 1 drop of ferric chloride solution a violet color. (b) To 50 mg of the acid taken in a dry test tube, add 10 drops each of methyl alcohol and conc. sulfuric acid and heat gently on a flame. Cool and pour the mixture into 5 ml of water taken in a small beaker odor of methyl salicylate (oil of wintergreen).
162 =-Naphthoic acid It is a crystalline solid, insoluble in cold water but soluble in hot water. (a) Heat 0.2 g of the acid with soda lime characteristic smell of napthalene. (b) Amide, m.p. 202°C (c) Anilide, m.p. 163°C
78
LABORATORY MANUAL OF ORGANIC CHEMISTRY
169 Tartaric acid HOOCCHOHCHOHCOOH It is a white crystalline compound. It is readly soluble in water and alcohol. (a) In a test tube, take 0.2 g of the acid and dissolve in 2 ml of water. To this add a few crystals of ferrous sulfate and shake. To this solution add 2 drops of hydrogen peroxide and 2 ml of 5% sodium hydroxide solution a deep violet color appears. (b) In a test tube mix 0.2 g of the acid, 0.2 g resorcinol and 2 ml conc. sulfuric acid mix well and heat the mixture a violet color appears. (c) Amide, m.p. 195°C (d) p-Toluidide, m.p. 264°C.
178 p-Toluic acid It is soluble in hot water and yields toluene on heating with soda lime. Amide, m.p. 158° C.
184 Anisic acid It is slightly soluble in water. On heating with soda lime it yields anisole, m.p. 154°C.
185 Succinic acid It is soluble in water. Place 20 mg of the substance in dry test tube and add twice the amount of resorcinol and 2 drops of conc. sulfuric acid. Gently heat the mixture till it is reddish-brown. Cool and add several drops of water followed by dil. sodium hydroxide solution till alkaline. Take 1 ml of this solution into another test tube and fill it with water a yellow green fluorescence.
186 p-Aminobenzoic acid It has yellowish-red crystals and is soluble in hot water. Heat a pinch of the substance with an equal amount of calcium chloride in a test tube. Cool and add 2 ml of ethanol a red solution.
195 Phthalic acid It is a white solid, soluble in hot water and sparingly soluble in ether and alcohol. (a) On heating above 150°C, it forms phthalic anhydride, m.p. 132°C.
TESTS FOR COMMON ORGANIC COMPOUNDS
79
(b) Mix 0.2 g of the acid with 0.4 g of resorcinol and add 1 ml of conc. sulfuric acid in a test tube. Heat the mixture on a flame till a red-brown in color. Cool and pour in cold water. Add a few drops of 10% sodium hydroxide solution orange-green fluorescence. (c) Amide, m.p. 220°C.
201 m-Hydroxybenzoic acid It is a colorless crystalline solid. It is insoluble in water but soluble in alcohol. It gives no color with ferric chloride solution. (a) The acid on heating with soda lime gives the smell of phenol. (b) Amide, m.p. 167° C (c) Acetate, m.p. 127° C (d) p-Toluidide, m.p. 163°C
214 p-Hydroxybenzoic acid
It is a colorless solid and has needle-like crystals. It is insoluble in water but soluble in alcohol and acetone. It gives a violet or red color with ferric chloride solution. (a) Amide, m.p. 162°C (b) Acetate, m.p. 185°C (c) p-Toluidide, m.p. 208°C
236 p-Chlorobenzoic acid It is a white solid and sparingly soluble in water. Amide, m.p. 179°C.
239 p-Nitrobenzoic acid It is a colorless substance soluble in organic solvents.
80
LABORATORY MANUAL OF ORGANIC CHEMISTRY
Heat 20 mg of the acid with twice the amount of soda-lime in a dry test tube odor of nitrobenzene.
251 p-Bromobenzoic acid It is colorless and sparingly soluble in hot water. Amide, m.p. 189°C.
5.3 ALDEHYDES AND KETONES b.p. (°C) 21
Acetaldehyde CH3CHO
It is miscible with water and has a pungent smell. In dilute aqueous solution the odor resembles that of apples. (a) To 20 ml of the aqueous solution add 2 ml of the 20% potassium hydroxide solution. Heat to boiling for 30 sec the solution turns yellow and then yellow precipitates appear changing to orange. (b) To 2 ml of the aqueous solution and 2 ml of sodium nitroprusside solution then add 5 drops of sodium hydroxide solution a deep wine red color.
49
Propionaldehyde CH3CH2CHO
It is soluble in water and has an odor resembling that of acetaldehyde. (a) To 2 ml of the aqueous solution add 1 ml of dil. sodium hydroxide solution. Boil for 1 min a white precipitate appears which dissolves to give a clear pale yellow solution. (b) 2,4-Dinitrophenylhydrazone, m.p. 155°C.
56
Acetone
It is miscible with water and has a pleasant odor. (a) With iodine solution and dil. sodium hydroxide solution, it yields iodoform (m.p. 119°C) in cold. (b) To 1 ml of aqueous solution of the substance add a few drops of sodium nitropruside solution a red color. (c) 2, 4-Dinitrophenylhydrazone, m.p. 128°C.
TESTS FOR COMMON ORGANIC COMPOUNDS
63
81
Isobutyraldehyde
It is soluble in cold water. 2,4-Dinitrophenylhydrazone, m.p. 182°C.
75
n-Butyraldehyde CH3CH2CH2CHO
It is soluble in cold water. 2,4-Dinitrophenylhydrazone (m.p. 122°C)
80
Methy ethyl ketone
It is miscible with water. 2,4-Dinitrophenylhydrazone, m.p. 111°C.
102 Diethyl ketone It is soluble in cold water 2,4-Dinitrophenylhydrazone, m.p. 143°C.
104 Crotonaldehyde CH3CH = CHCHO It is fairly soluble in cold water and has a pungent odor. (a) To 2 ml of the aqueous solution add 2 ml of dil. sodium hydroxide solution and boil for 30 sec a yellow solution followed by a yellow precipitate turning to orange. (b) To 2 ml of the aqueous solution add 2 ml of sodium nitroprusside solution followed by 1 drop of sodium hydroxide solution a deep wine red color. (c) 2,4-Dinitrophenylhydrazone, m.p. 190°C.
115 p-Hydroxybenzaldehyde It is sparingly soluble in water. To 1 ml of aqueous solution in a test tube add 1 drop of ferric chloride solution a faint violet color. Semicarbazone, m.p. 224°C.
130 Cyclopentanone 2,4-Dinitrophenylhydrazone, m.p. 146°C.
82
LABORATORY MANUAL OF ORGANIC CHEMISTRY
139 Acetyl acetone It is soluble in water and yields an orange-red color with ferric chloride solution. On passing ammonia gas through the ethereal solution of the ketone, ammonium salt is formed, m.p. 65°C.
155 Cyclohexanone It is soluble in cold water. In a 100 ml round-bottomed flask add 1 ml of the substance and 30 ml potassium dichromate solution. Heat to boiling for 5 min. Cool and filter and acidify the filtrate with conc. hydrochloric acid. Filter the adipic acid formed, m.p. 150°C.
179 Benzaldehyde It is strongly soluble in water and has an odor of bitter almonds. (a) It is oxidized by potassium permanganate to benzoic acid, m.p. 121°C. (b) It does not reduce Fehlings solution. (c) In a boiling tube place 1 ml of benzaldehyde, 5 drops of acetone and 5 ml of alcohol and 2 ml of dil. sodium hydroxide solution. Boil the contents for 1 min. Cool and shake vigorously and then dilute with 20 ml of water. Shake and filter the yellow solid dibenzalacetone (C6H5CH=CH2) 2CO, m.p. 112°C.
196 Salicyldehyde It is sparingly soluble in water and gives a violet color with ferric chloride solution. It is oxidized by alkaline potassium permanganate solution to salicylic acid, m.p. 155°C.
202 Acetophenone It is sparingly soluble in water. On oxidation with alkaline potassium permanganate solution it yields benzoic acid, m.p. 121°C. Add 2 drops of the ketone to 2 ml of sodium nitroprusside solution followed by 2 drops of sodium hydroxide solution a wine red color.
TESTS FOR COMMON ORGANIC COMPOUNDS
83
207 Menthone
It is miscible with water and has an odor of peppermint. Semicarbazone, m.p. 184°C.
210 Propiophenone Semicarbazone, m.p. 174°C.
220 Cinnamaldehyde It is insoluble in water and has the odor of cinnamon. (a) On warming with conc. potassium hydroxide solution, it yields cinnamic acid
(m.p. 133°C) and cinnamyl alcohol (b.p. 254°C). Cinnamyl alcohol can be separated
by extracting the mixture with ether and the acid is recovered by acidifying the aqueous solution. (b) It is oxidized by alkaline potassium permanganate solution to benzoic acid, m.p. 121°C.
225 p-Methylacetophenone (a) It gives the same test (a) as under acetophenone. (b) Semicarbazone, m.p. 205°C.
232 p-Chloroacetophenone It is oxidized to p-chlorobenzoic acid, m.p. 236°C.
84
LABORATORY MANUAL OF ORGANIC CHEMISTRY
248 Citral
It possesses an odor of lemon and forms an addition compound on shaking with an aqueous solution of sodium bisulfite. Semicarbazone, m.p. 164°C.
248 p-Anisaldehyde It is insoluble in water. In a 250 ml round-bottomed flask place 250 mg of potassium permanganate and 50 ml of water. Heat to dissolve and cool the solution. Add 1 ml of the aldehyde. Gently shake until the color of potassium permanganate disappears. Cool, filter and acidify the filtrate with conc. hydrochloric acid. Filter the anisic acid, wash with cold water and dry, m.p. 184°C.
252 Cinnamaldehyde It is a colorless oily liquid. It possesses cinnamon odor. It is insoluble in water but soluble in ether. (a) Take 2 ml of the Tollens reagent in a test tube and to it add 0.1 g of the aldehyde. Shake and place in boiling water for 5 min appearance of silver mirror along the sides of the tube. (b) To 2 ml of bromine water in a test tube, add 0.1 g of the substance and shake disappearance of bromine color. (c) Oxime, m.p. 138°C. (d) Phenyl hydrazone, m.p. 168°C.
m.p. (°C)
44
o-Nitrobenzaldehyde
It is yellow in color, slightly soluble in water but soluble in most organic solvents. With potassium permanganate it is oxidized to o-nitrobenzoic acid, m.p. 147°C. Oxime, m.p. 58°C.
TESTS FOR COMMON ORGANIC COMPOUNDS
47
85
p-Chlorobenzaldehyde
Oxidation with potassium permanganate solution yields p-chlorobenzoic acid, m.p. 236°C, 2, 4-dinitrophenylhydrazone m.p. 265°C.
48
Benzophenone
It is insoluble in water and forms a yellow solution in conc. sulfuric acid. (a) Fuse a pinch of the compound with a small piece of sodium metal blue color. (b) 2, 4-Dinitrophenylhydrazone, m.p. 265°C.
56
Chloral hydrate Cl3CCH(OH)2
It has an odor resembling that of cucumber. In a test tube place 70 mg of resorcinol, 2 ml of dil. sodium hydroxide solution and 20 mg of the substance and heat to boiling red color.
58
m-Nitrobenzaldehyde
It is pale yellow, slightly soluble in water. (a) With potassium permanganate it yields m-nitrobenzoic acid, m.p. 140°C (b) Oxime, m.p. 140°C.
134 Benzoin It is insoluble in water. To 100 mg of the substance in a test tube add 1 ml of Fehlings solution and 1 ml of water. Heat to boiling for 30 sec a red precipitate of cupric oxide.
179 Camphor It is insoluble in water and possesses a characteristic odor. Oxime, m.p. 118°C.
86
LABORATORY MANUAL OF ORGANIC CHEMISTRY
5.4 ESTERS b.p. (°C)
57
Methyl acetate
It is colorless liquid. It has fruity smell, soluble in cold water and alcohol. d 0.939
77
Ethyl acetate
It is colorless and soluble in cold water and alcohol. In a 50 ml round-bottomed flask place 1 g of the compound and 20 ml of potassium hydroxide solution. Reflux for 20 min. Distil off the ethyl alcohol and perform the iodoform test with the distillate.
79
Methyl propionate (a) 3, 5-Dinitrobenzoate, m.p. 108°C.
98
Ethyl propionate (a) 3, 5-Dinitrobenzoate, m.p. 88°C.
120 Ethyl n-butyrate
126 n-Butyl acetate
140 n-Butyl propionate
TESTS FOR COMMON ORGANIC COMPOUNDS
87
148 n-Amyl acetate It is a colorless, insoluble in water but soluble in alcohol. d 0.875
170 Ethyl acetoacetate It is colorless has pleasant odor. Sparingly soluble in water but soluble in ether and alcohol. d 1.028 Dissolve 0.1 g of the ester in water by shaking. Add 1 drop of ferric chloride solution red color.
185 Diethyl oxalate It is slightly soluble in water. With excess ammonium hydroxide it yields an oxamide which sublimes without melting.
195 Methyl succinate It is soluble in cold water. d 1.120
197 Phenyl acetate It is insoluble in water and possesses a sweet smell. To 20 mg of the substance add 2 ml of water, boil and add 1 drop of ferric chloride solution blue color.
199 Methyl benzoate It is colorless, in soluble in water. On hydrolysis with dil. hydrochloric acid it yields benzoic acid, m.p. 121°C d 1.089
88
LABORATORY MANUAL OF ORGANIC CHEMISTRY
213 Ethyl benzoate It is a colorless sweet-smelling liquid. On addition of conc. nitric acid to a cold solution in conc. sulfuric acid of the ester, ethyl m-nitrobenzoate is formed, m.p. 217° C. d 1.047
218 Diethyl succinate It is colorless soluble in alcohol. d 1.042
220 Methyl phenylacetate It is colorless, soluble in alcohol. d 1.068
223 Methyl salicylate It is a colorless compound. It smells like winter green oil (an aromatic liquid distilled from the leaves of wintergreen plant) . It is insoluble in water but soluble in alcohol and ether.
228 Ethyl phenylacetate
271 Ethyl cinnamate It is a colorless, insoluble in water but soluble in alcohol. d 1.049 It decolorizes bromine water.
TESTS FOR COMMON ORGANIC COMPOUNDS
89
m.p. (°C)
36
Methyl cinnamate
It is colorless, insoluble in water, soluble in hot alcohol. It decolorizes aqueous bromine solution.
37
Ethyl mandelate
With ammonium hydroxide it yields an amide, m.p. 131°C
42
Phenyl salicylate (Salol)
It is colorless, insoluble in water but soluble in hot alcohol. It gives no color with ferric chloride solution. Acetyl derivative (m.p. 97°C).
45
Methyl anisate
51
Methyl oxalate
It is colorless, insoluble in water but soluble in hot alcohol.
58
Methyl mandelate
With conc. ammonium hydroxide it yields amide, m.p. 131°C.
90
68
LABORATORY MANUAL OF ORGANIC CHEMISTRY
Phenyl benzoate
It is colorless, insoluble in water but soluble in hot alcohol.
70
Methyl p-hydroxybenzoate
It gives a red color with ferric chloride solution.
78
Phenyl cinnamate
116 Ethyl p-hydroxybenzoate It gives violet color with ferric chloride solution. Benzoyl derivative, m.p. 89°C.
5.5 AMINES b.p. (°C) 17
Ethylamine C2H5NH2
It is soluble in water, alcohol and ether. It has an ammoniacal odor. (a) Benzoyl derivative, m.p. 71°C.
49
n-Propylamine CH3CH2CH2NH2
It is miscible with water, alcohol and ether. (a) Hydrochloride, m.p. 159°C.
55
Diethylamine
It possesses a fish-like odor. It is soluble in water and alcohol. Add one drop of the compound to 2 ml of sodium nitropruside solution followed by 1 ml freshly prepared solution of acetaldehyde in water a deep blue color.
TESTS FOR COMMON ORGANIC COMPOUNDS
77
91
n-Butylamine CH3CH2CH2CH2NH2
It is miscible with water. d 0.741 Hydrochloride, m.p. 195°C.
89
Triethylamine
It is miscible with water in all proportions. Picrate, m.p. 173° C.
105 Piperidine It is miscible with water and has an unpleasant odor. p-Toluenesulfonyl derivative, m.p. 100°C.
184 Aniline It is insoluble in water. (a) It responds to carbylamine test with potassium hydroxide and chloroform. (b) Acetyl derivative, m.p. 113°C.
185 Benzylamine C6H5CH2NH2 It is miscible with water. Acetyl derivative, m.p. 60°C.
193 Methyl aniline C6H5NHCH3 Hydrochloride, m.p. 121°C.
199 m-Toluidine (a) Dissolve 2 drops of the substance in 2 ml of 50% sulfuric acid and add a few drops of potassium dichromate solution a yellow-brown color. (b) Acetyl derivative, m.p. 65°C.
92
LABORATORY MANUAL OF ORGANIC CHEMISTRY
200 o-Toluidine It is soluble in cold water. (a) In a test tube dissolve 2 drops of the substance in 2 ml of 50% sulfuric acid. Add a few drops of potassium dichromate solution a blue color. (b) Acetyl derivative, m.p. 112°C.
209 o-Chloroaniline It is a colorless, insoluble in water, soluble in alcohol. It responds to the dye test. (a) It forms a dye with >-naphthol on diazotisation. (b) Benzoyl derivative, m.p. 99°C.
230 m-Chloroaniline It is colorless, insoluble in water but soluble in alcohol and gives the dye test with >-naphthol. Acetyl derivative, m.p. 72°C.
251 m-Bromoaniline It is colorless, insoluble in water but soluble in alcohol. It gives the dye test with >-naphthol. Acetyl derivative, m.p. 87°C.
m.p. (°C)
32
o-Bromoaniline
It is colorless, insoluble in water but soluble in alcohol and ether. It responds to the dye test with >-naphthol. Acetyl derivative, m.p. 99°C.
TESTS FOR COMMON ORGANIC COMPOUNDS
45
93
p-Toluidine
It has a powerful characteristic odor and is soluble in water. (a) To 1 ml of 50% sulfuric acid in a test tube add a pinch of the compound yellow color. (b) With bromine it yields a 2, 6-dibromo derivative, m.p. 73°C.
51
p-Anisidine
It is sparingly soluble in water but soluble in alcohol. It gives the dye test with >-naphthol. (a) Solution of its hydrochloride in water yields violet color with ferric chloride solution. (b) Acetyl derivative, m.p. 127°C.
54
Diphenylamine C6H5NHC6H5
It is insoluble in water but soluble in alcohol. (a) Dissolve 20 mg of the compound in conc. sulfuric acid then add a drop of sodium nitrite solution a blue color. (b) Dissolve another 20 mg of the substance in 1 ml hydrochloric acid and add a few drops of HNO3 a deep blue coloration.
60
=-Naphthylamine
It possesses a bad odor and is slightly soluble in hot water. (a) Its hydrochloride dissolves in water to give a blue precipitate with ferric chloride solution. (b) Picrate, m.p. 161°C.
66
p-Bromoaniline
It is a colorless substance insoluble in water, soluble in alcohol. It responds to the dye test with >-naphthol. Acetyl derivative, m.p. 167°C.
94
70
LABORATORY MANUAL OF ORGANIC CHEMISTRY
p-Chloroaniline
It is soluble in hot water and alcohol. It gives the dye test with >-naphthol. Acetyl derivative, m.p. 179°C.
71
o-Nitroaniline
It is orange yellow in color. It is soluble in hot water, alcohol and ether. It gives the dye test with >-naphthol. Acetyl derivative, m.p. 92°C.
78
s-Trichloroaniline
It is colorless, soluble in alcohol and ether. (a) It responds to the dye test.
113 >-Naphthylamine It is an odorless but pink colored compound and sparingly soluble in hot water with >naphthol. (a) It does not give a blue precipitate with ferric chloride solution. (b) Acetyl derivative, m.p. 132°C.
114 m-Nitroaniline It possesses a yellow color and soluble in hot water. It responds to the dye test. Acetyl derivative, m.p. 155°C.
140 p-Phenylenediamine It is colorless and darkens on exposure. Sparingly soluble in water but soluble in alcohol.
TESTS FOR COMMON ORGANIC COMPOUNDS
95
(a) It responds to the dye test with >-naphthol. (b) Acetyl derivative, m.p. 305°C.
147 p-Nitroaniline It is yellow in color and soluble in hot water. It gives the dye test with >-naphthol. Acetyl derivative, m.p. 215°C.
5.6 AMIDES AND ANILIDES b.p. (°C)
105 Formamide It is soluble in water. On heating it decomposes evolving ammonia gas. (a) To 2 ml of mercuric chloride solution add 1 drop of the compound and heat to boiling for 30 sec a white precipitate of mercurous chloride is obtained. (b) Dissolve 25 mg of the substance in 2 ml of water and then add 2 drops of ferric chloride solution a wine-red color which on heating forms a brown precipitate.
m.p. (°C)
79
Propionamide
It is soluble in water and ether. (a) With 75% sulfuric acid at 120°C it yields propionic acid, b.p. 140°C. (b) One heating with aniline it yields propionanilide, m.p. 103°C.
82
Acetamide
It is readily soluble in water and alcohol. (a) To 2 ml of the aqueous solution, add an equal volume of ferric chloride solution a wine red color yielding a reddish brown precipitate on warming. (b) Picrate, m.p. 107°C.
96
LABORATORY MANUAL OF ORGANIC CHEMISTRY
114 Acetanilide It is soluble in hot water. With 1 mole of bromine in acetic acid it yields p-bromo derivative, m.p. 167°C.
115 n-Butyramide It is readily soluble in water, alcohol and ether. On heating with aniline it yields n-butyranilide, m.p. 90°C.
129 Benzamide It is sparingly soluble in cold water. Mix 50 mg of the substance with three times its amount of soda lime. Introduce the mixture in an ignition tube and heat odor of benzonitrile ( bitter almonds).
133 Salicylamide It is a yellow crystalline solid, sparingly soluble in cold water. (a) It gives violet color with ferric chloride solution. (b) Acetyl derivative, m.p. 143°C.
157 Phenylacetamide It is a colorless substance and sparingly soluble in water. In a boiling tube place 50 mg of the compound and 2 ml of dil. hydrochloric acid. Boil and cool the solution. Neutralize with sodium hydroxide solution and filter the phenylacetic acid, m.p. 76°C.
162 Benzanilide It is colorless or reddish compound, sparingly soluble in alcohol. (a) In a test tube boil 0.5 g of the solid with dil. hydrochloric acid benzoic acid is formed.
TESTS FOR COMMON ORGANIC COMPOUNDS
97
(b) Add bromine solution to 0.5 g of the anilide in a test tube p-bromoanilide, m.p. 204°C.
176 o-Nitrobenzamide It is colorless and soluble in hot water and alcohol. (a) Heat 0.5 g of the amide with sodium hydroxide solution and acidify, o-Nitrobenzoic acid, m.p. 147°C. (b) Boil 0.5 g of the amide in the presence of Sn/HCl anthranilic acid, m.p. 144° C.
192 Biuret NH2CONHCONH2 It is soluble in cold water. (a) Heat 50 mg of the compound in a dry test tube above the melting point strong smell of ammonia gas. (b) To 1 ml of the aqueous solution add an equal volume of copper sulfate solution violet color.
201 p-Nitrobenzamide It is colorless, soluble in hot water and alcohol. (a) Heat 0.5 g of the amide with sodium hydroxide solution and acidifyp-nitrobenzoic acid, m.p. 186°C. (b) On reduction, yields p-aminobenzoic acid, m.p. 186°C.
219 d-Phthalamide It is a colorless substance, sparingly soluble in water. (a) On heating above its melting point ammonia gas is evolved. (b) Place 25 mg of the substance in a dry test tube, add 2 drops of conc. sulfuric acid and warm. Add 50 mg of resorcinol and again heat the mixture gently till it attains a reddish-brown color. Cool and add a few drops of water followed by dil. sodium hydroxide solution till alkaline. Take 1 ml of this solution into another test tube and fill it up with water a green fluorescence.
98
LABORATORY MANUAL OF ORGANIC CHEMISTRY
233 Phthalimide
It is a colorless compound, insoluble in water but soluble in absolute alcohol. (a) It responds to fluorescence test. (b) N-acetate derivative, m.p. 133°C. (c) N-benzoate derivative, m.p. 115°C.
242 Succinamide It is soluble in hot water but insoluble in alcohol and ether. (a) It responds to test (a) as listed for phthalamide. (b) On heating it decomposes to give ammonia and succinimide, m.p. 125°C.
418 Oxamide It is insoluble in water, alcohol or ether. (a) In a test tube place 25 mg of the compound and 5 ml of dil. sodium hydroxide solution. Boil for 30 sec. Acidify the warm solution with glacial acetic acid. Add
23 drops of calcium chloride solution immediately a white precipitate (calcium oxalate) appears.
(b) In a test tube place 75 mg of the compound and 2 ml of dil. sodium hydroxide
solution, followed by 2 drops of copper sulfate solution (Fehlings solution No. 1 ) and shake pink color.
5.7 ARYL HALIDES b.p. (°C)
132 Chlorobenzene It is a colorless, pleasant smelling liquid, insoluble in water but soluble in alcohol, ether or benzene. Chlorbenzene responds to the Beilstein test.
TESTS FOR COMMON ORGANIC COMPOUNDS
99
On warming to 80°C with conc. nitric acid (1 mole) and conc. sulfuric acid it yields p-nitro derivative (m.p. 83°C).
157 Bromobenzene It is slightly colored and pleasant smelling liquid. Insoluble in water but soluble in alcohol and ether. With conc. nitric acid and sulfuric acid at room temperature, it yields a p-nitro derivative, m.p. 120°C. Bromobenzene responds to the Beilstein test.
159 o-Chlorotoluene It is colorless, insoluble in water but soluble in benzene and ether. On oxidation with potassium permanganate solution, it yields o-chlorobenzoic acid, m.p. 140°C.
162 m-Chlorotoluene It is colorless and insoluble in water but soluble in benzene and ether. On oxidation with alkaline potassium permanganate solution yields, m-chlorobenzoic acid, m.p. 153°C.
162 p-Chlorotoluene It is a colorless liquid, insoluble in water, but soluble in benzene and ether. On oxidation with alkaline potassium permanganate solution, it gives p-chlorobenzoic acid, m.p. 236°C.
181 o-Bromotoluene It is colorless, insoluble in water but soluble in ether and alcohol. (a) On oxidation with alkaline potassium permanganate solution, it yields obromobenzoic acid, m.p. 147°C. In a 100 ml round-bottomed flask place 1 ml of the compound and 2.5 g solid potassium permanganate. To the mixture add 40 ml of water, 5 drops of sodium
100
LABORATORY MANUAL OF ORGANIC CHEMISTRY
hydroxide solution. and reflux for 3 hr. Cool and pass sulfur dioxide gas until any purple color and brown precipitate have disappeared. Filter off the white solid, wash with cold water) o-bromobenzoic acid is obtained, m.p. 147°C.
183 m-Bromotoluene It is colorless, insoluble in water, soluble in alcohol. It is oxidized to m-bromobenzoic acid, m.p. 251°C.
m.p. (°C)
53
p-Dichlorobenzene
It has a characteristic odor. It is colorless solid and insoluble in water, soluble in alcohol and ether. Nitration with conc. nitric acid yields, 1,4-dichloro-2-nitrobenzene, m.p. 54°C.
89
p-Dibromobenzene
It is a white crystalline solid, possesses characteristic aromatic odor and insoluble in water but soluble in benzene and ether. Immerse a 50 ml round-bottomed flask in ice-cold water and charge it with 1 ml of the substance, add 2 ml each of ice-cold conc. nitric acid and conc. sulfuric acid through a dropping funnel dropwise. After the addition is complete keep the flask in a hot water-bath for 15 min. Cool and pour the mixture on ice cold water. Crystallize the solid 1,4-dibromo2-nitrobenzene from ethanol, m.p. 126° C.
119 Iodoform
CHI3
It has a characteristic yellow color and possesses an unpleasant odor. It is insoluble in water but soluble in alcohol and ether. (a) Heat 0.1 g of the compound in a test tube violet color due to the evolution of iodine appears. (b) To 0.1 g of the compound in a test tube add 1 ml of alcohol and 2 drops of silver nitrate solution a yellow precipitate. (c) Take 0.2 g of the compound in a test tube, add 1 g of resorcinol and 2 ml of alcoholic sodium hydroxide solution and warm in a beaker of hot water a red color changing to violet.
TESTS FOR COMMON ORGANIC COMPOUNDS
101
5.8 MISCELLANEOUS COMPOUNDS b.p. (°C)
83
Cyclohexene
To 1 ml solution of bromine solution in carbon tetrachloride in a test tube, add 2 drops of the compound immediate decolorization of bromine color. On oxidation with conc. nitric acid it yields adipic acid, m.p. 152°C.
210 Nitrobenzene It is yellow liquid with odor of bitter almonds and insoluble in water. It is soluble in organic solvents. (a) On warming with fumming nitric acid and conc. sulfuric acid it yields m-dinitrobenzene, m.p. 90°C. (b) Boil 1 ml of the compound with 4 ml of stannous chloride solution in conc. hydrochloric acid. To 2 ml of the resulting aniline solution add sodium nitrite solution. Cool and add alkaline solution of >-naphthola scarlet red dye.
220 o-Nitrotoluene It is a pale yellow liquid, smells like nitrobenzene and insoluble in water. (a) In a test tube place 2 drops of the substance and 2 drops of dil. sodium hydroxide solution a deep red color. (b) On oxidation with potassium permanganate solution, it yields o-nitrobenzoic acid, m.p. 147°C.
265 o-Nitroanisole It is insoluble in water but miscible with organic solvents. With conc. nitric acid and sulfuric acid at 0°C, it yields 2,4-dinitro derivative, m.p. 88°C.
102
LABORATORY MANUAL OF ORGANIC CHEMISTRY
268 o-Nitrophenetol It is insoluble in water but miscible with organic solvents. With conc. nitric acid and sulfuric acid, it yields, 2, 4-dinitro derivative, m.p. 86°C.
m.p. (°C)
36
Azoxybenzene
It has bright yellow needles, insoluble in water but soluble in alcohol and ether. In aqueous alcoholic solution, with zinc dust forms orange-red colored azobenzene, m.p. 68°C and then hydrazobenzene, m.p. 131°C.
54
p-Nitroanisole
Insoluble in water but soluble in alcohol and ether. With fuming nitric acid, it yields a 2, 4-dinitro derivative, m.p. 88°C.
54
p-Nitrotoluene
It is very pale yellow solid and has an odor like nitrobenzene. It is insoluble in water but soluble in alcohol.
59
p-Nitrophenetol
It is insoluble in water, sparingly soluble in cold alcohol but readily soluble in ether. With conc. nitric acid and sulfuric acid in cold, it yields a 2, 4-dinitro derivative, m.p. 76°C.
65
Benzenesulfonic acid
It is readily soluble in water. Benzenesulfonamide, m.p. 153°C.
68
Azobenzene C6H5N=NC6N5
It is orange-red in color and sparingly soluble in water.
TESTS FOR COMMON ORGANIC COMPOUNDS
103
(a) When treated with bromine in acetic acid it gives a dibromo derivative, m.p. 187°C. (b) With zinc dust and sodium hydroxide it yields hydrazobenzene, m.p. 131°C.
69
p-Toluenesulfonyl chloride
On boiling with water, it yields p-toluenesulfonic acid, m.p. 92°C.
115 p-Benzoquinone It has a characteristic pungent odor. (a) Dissolve 20 mg of the compound in 1 ml of potassium hydroxide solution, the solution turns brown on standing. (b) It reduces ammoniacal silver nitrate solution, forming a silver mirror. (c) In a test tube place 20 mg of the compound and an equal amount of ferous sulfate. Add 2 ml of dil. sulfuric acid and shake. Add 5 ml of water and warm. A clear yellow solution is obtained. Allow the test tube to stand in cold water for some time green needles of hydroquinone are formed.
137 p-Toluenesulfonamide It is sparingly soluble in cold water but soluble in dil. sodium hydroxide solution, ether or alcohol. (a) On treatment with a mixture of benzyl chloride and sodium hydroxide in alcohol, it yields a benzyl derivative, m.p. 116°C. (b) On oxidation with potassium permanganate solution it produces p-sulfonamidobenzoic acid, m.p. 280°C.
153 Benzenesulfonamide It is sparingly soluble in water but soluble in alcohol and ether. (a) With benzyl chloride ( 1 mol) and sodium hydroxide in alcohol, it yields the benzyl derivative, m.p. 88°C.
104
LABORATORY MANUAL OF ORGANIC CHEMISTRY
153 o-Toluenesulfonamide It is sparingly soluble in cold water but soluble in alcohol and ether. With 75% sulfuric acid it yields toluene, b.p. 110°C.
198 Aniline hydrochloride It is a colorless substance but turns black on storage. It is soluble in water but insoluble in benzene or ether. Dissolve 25 mg of the substance in distilled water in a test tube and a few drops of silver nitrate solution and shake heavy white precipitate of silver chloride.
300 Sulfanilic acid It is a white crystalline solid, soluble in hot water. (a) To 25 mg of the substance add 2 ml of potassium dichromate solution and dil. sulfuric acid and heat to boiling pungent odor of p-benzoquinone. (b) To a solution of 50 mg of the compound in hot water add bromine solution (10 ml bromine) and 1.5 g potassium bromide in 100 ml water. Stir till the liquid is pale yellow. Filter the solid, wash with cold water and dry, 2,4,6-tribromoaniline, m.p. 199°C.
Chapter
6
PREPARATION OF DERIVATIVES
The tests in the preceding chapters help to recognize the unknown into its specific class such as an aldehyde, amine or a carboxylic acid. Then the physical properties of the unknown are compared with those of the representative compounds. Such a comparison often presents several possibilities. The choice, however, can be narrowed down by preparing a derivative. A derivative is usually a solid material which can readily be prepared from the unknown and can be easily isolated and purified. Moreover, it should be crystalline and differ in physical properties from the unknown. Formation of a derivative involves a reaction between the functional group and another reagent. It is thus desirable that the reaction be accomplished in a short period and conditions are controllable. Prepare the derivatives carefully because you are working with small amounts of compounds. Always recrystallize till a constant melting point is obtained. The melting point of a derivative can be used as a proof for the identity of the unknown. A description of various derivatives is intended in this chapter.
6.1 DERIVATIVES OF ALCOHOLS Several types of derivatives can be prepared for the characterization of both alcohols and phenols.
(a) Acetates Acetate esters are particularly useful in the characterization of polyhydric alcohols and are usually easy to prepare.
106
LABORATORY MANUAL OF ORGANIC CHEMISTRY
Procedure: In a boiling tube place 0.5 g (10 drops of the liquid) of alcohol sample, 4 ml pyridine and add 2 ml of freshly distilled acetic anhydride with shaking. Heat the mixture on a water-bath for 5 min. Pour the contents onto ice taken in a beaker and filter off the solid, wash it with dil. hydrochloric acid to remove pyridine. Finally wash with cold water. Recrystallize from hot aqueous ethanol. Take the melting point and compare from the tables.
(b) p-Nitrobenzoates This is generally the most useful ester derivative for the characterization of alcohols.
Procedure: In a small test tube place 0.5 g (10 drops of the liquid ) of alcohol sample, 4 ml pyridine and 1 g p-nitrobenzoyl chloride. Heat the contents for 10 min and pour the mixture on ice water. Filter off the solid on a Buchner funnel, wash with dil. hydrochloric acid to remove pyridine. Recrystallize from aqueous ethanol. Both the above reactions proceed well with primary and secondary alcohols but not with tertiary alcohols.
Question 6.1 Why do tertiary alcohols not react with p-nitrobenzoyl chloride?
(c) =-Naphthylcarbamates (urethane) =-Naphthyl urethane is another useful derivative for the characterization of alcohols.
Procedure: Take the unknown alcohol 1 g (1 ml if liquid) in a dry test tube and to it add 0.5ml of =-naphthyl isocyanate. Shake the contents and allow the tube stand at room temperature for 5 min with occasional shaking. A solid should appear after this period. In case no solid is formed warm on a water-bath and cool again. Scratch the sides of the tube if necessary. Filter the solid and recrystallize from light petroleum.
PREPARATION OF DERIVATIVES
107
6.2 DERIVATIVES OF PHENOLS As a general rule the derivatives prepared for alcohols can be prepared and are useful for phenols as well. Acetates and p-nitrobenzoates can be prepared as in the case of alcohols. In addition, the following derivative may also be useful.
(a) Benzoates The hydroxyl group of phenols can be esterified by the Schötten-Baumann reaction using benzoyl chloride and a base.
Procedure: Place 0.5 ml of the phenol in 2.5 ml of water in a test tube. To this add 2.5 ml of 10% of sodium hydroxide solution followed by 0.3 ml of benzoyl chloride. Stopper the tube and shake for several minutes. The odor of benzoyl chloride should disappear. Collect the solid on a Buchner funnel and wash with cold water. Recrystallize from hot alcohol.
Question 6.2 Write a mechanism for the Schötten-Baumann reaction.
(b) 3, 5-Dinitrobenzoates 3, 5-Dinitrobenzoate esters are useful for both phenols and alcohols.
Procedure: In a 100 ml round bottomed flask equipped with a reflux condenser, place 0.5 g of phenol, 5 ml of pyridine and 1.3 g of 3, 5-dinitrobenzoyl chloride and reflux the mixture gently for 30 min. Cool the contents and pour onto 50 ml of 5% sulfuric acid. Shake the mixture, filter the solid and wash with water. Suspend the solid in 50 ml of 5% sodium hydroxide solution to remove any 3, 5-dinitrobenzoic acid and filter again. Recrystallize the derivative from hot aqueous ethanol.
108
LABORATORY MANUAL OF ORGANIC CHEMISTRY
6.3 DERIVATIVES OF ALDEHYDES AND KETONES These two classes of compounds react with similar reagents to form crystalline solids.
(a) 2, 4-Dinitrophenylhydrazones 2, 4-Dinitrophenylhydrazones, semicarbazones, oximes, etc. are colored solids and have sharp melting points.
Procedure: Place 0.2 g of 2, 4-dinitrophenylhydrazine and 10 ml of ethanol in an Erlenmeyer flask. To this add 5 drops of conc. sulfuric acid and warm to complete the solution. Cool and add 0.2 g of unknown aldehyde (or ketone) dissolved in 1 ml ethanol. Warm the contents in water-bath for 12 min. and then allow to stand for 15-30 min at room temperature. If no solid separates then add water till precipitation is complete. Filter and recrystallize the solid from aqueous ethanol. Alternatively if 2, 4-dinitrophenylhydrazine reagent is provided then proceed as follows: Dissolve 0.2 g of aldehyde (ketone ) in 2 ml of 95% ethanol. To this add 2 ml of the reagent. Shake the mixture vigorously. If a precipitate does not form immediately allow to stand for 15 min. Filter and crystallize the solid from aqueous ethanol. To make a 2, 4-DNP derivative of acetone, instead add acetone dropwise to 2, 4-DNP solution in a test tube, as the derivative is soluble in acetone. In the case of acetophenone if an oily layer persists, keep the tube in ice and stir. The derivative will precipitate out.
Question 6.3 Why is adjustment of pH essential in the above reaction?
(b) Semicarbazones Semicarbazones are easily formed and have sharp melting points.
Procedure: Place 0.5 g of semicarbazide hydrochloride, 0.8 g of sodium acetate, 5 ml of
water and 1 ml of ethanol in a test tube. To this add 500 mg (0.5 ml) of aldehyde or ketone.
PREPARATION OF DERIVATIVES
109
Shake the mixture for a few minutes then warm in a beaker containing water at 7075°C for 10 min. and then allow to cool. The semicarbazone precipitates out from the cold solution on standing. Recrystallize the derivative from hot aqueous ethanol.
(c) Phenylhydrazones
Procedure: Dissolve 0.4 g of phenylhydrazine in 1.5 ml of water and add solution of 0.2 g of aldehyde or ketone dissolved in 5 ml ethanol. Boil the mixture for 1 min, add 2 drops of glacial acetic acid and boil again for 5 min. Cool and add water till a solid separates out. Filter the solid and recrystallize from hot ethanol.
(d) Oximes Aldehydes and ketones form crystalline oxime derivatives on reaction with hydroxylamine hydrochloride.
Procedure: In a test tube, dissolve 0.5 g hydroxylamine hydrochloride and 1 g of sodium acetate in 2 ml water. To the solution add 0.2 g of the unknown carbonyl compound. In case the compound is not soluble in water add ethanol dropwise till a clear solution is obtained. Warm the contents on a water-bath for 15 min and then cool in ice. If a solid does not appear scratch the sides of the tube with a glass rod. Filter the solid and recrystallize from hot aqueous ethanol.
6.4 DERIVATIVES OF CARBOXYLIC ACIDS (a) s-Benzylisothiouronium salts This reaction should not be performed if the solution is alkaline, otherwise benzylthiol is liberated which has obnoxious odor.
Procedure: Dissolve or suspend 0.25 g of the acid in 1 ml of water in a test tube. Add 1 drop of phenolphthalein indicator and then neutralize with 1 N sodium hydroxide solution till a
110
LABORATORY MANUAL OF ORGANIC CHEMISTRY
pink color is obtained. Add 3 drops of 0.1 N hydrochloric acid till the solution is neutral. Now add 1 g of s-benzylisothiouronium chloride dissolved in 3 ml of water. Cool the mixture in an ice-bath. Filter the solid and recrystallize from hot aqueous ethanol. The solution at this stage should become faintly pink. Make sure the solution is neutral.
(b) Amides Amides are useful drivatives of carboxylic acids and can be easily prepared.
Procedure: In a mortar, grind together 0.5 g of the unknown acid and 2 g of phosphorus pentachloride until the mixture becomes liquid. To the crude acid chloride so obtained add slowly 10 ml of liquor ammonia. After the vigorous reaction has stopped, stir and cool. Filter the solid and wash with cold water and recrystallize from hot ethanol.
Question 6.4 Why are amides preferably prepared by the above method and not by treatment of acids with NH3 followed by heating?
(c) Anilides and p-toluids These two derivatives can be prepared by reacting an acid chloride with aniline or p-toluidine.
Procedure: Take 1 g of the unknown acid and prepare the acid chloride either by using PCl5 as in the above experiment or the acid for 30 minutes with 2.5 ml of thionyl chloride in a small round bottom flask. Cool the acid chloride solution and to this add 2 g of amine solution in 20 ml benzene and warm the mixture in a hot water-bath. Cool and transfer the solution in a separatory funnel. Wash the benzene layer successively with 2 ml water, 5 ml of 5 % hydrochloric acid,
PREPARATION OF DERIVATIVES
111
5 ml of 5% sodium hydroxide solution and finally with 5 ml water. Distil benzene and recrystallize the residue from alcohol.
(d) p-Bromophenacyl esters
Procedure: Neutralize with 10% sodium hydroxide solution, a 0.5 g of the acid suspended in 3 ml of water. To this add 5 ml of ethyl alcohol and 0.5 g of p-bromophenacyl bromide and reflux for 1 hr. Cool and collect the solid, wash with water and recrystallize from hot ethanol.
6.5 DERIVATIVES OF ESTERS In the identification of an ester we are faced with the problem of identifying the acid as well as the alcoholic component. The ester can, therefore, be hydrolyzed with dil. sodium hydroxide solution and the acid as well as the alcohol portions are separated and their derivatives prepared. Alternatively, the 3,5-dinitrobenzoate derivative of the unknown ester may be prepared.
Procedure: Mix 2 ml of the ester with 1.5 g of 3,5-dinitrobenzoic acid and 2 drops of conc. sulfuric acid in a 50 ml round bottom flask fited with a reflux condenser. Heat the mixture in an oil-bath at 150°C for 45 min. Cool and add 25 ml ether and transfer the solution to a separatary funnel. Wash the ethereal solution with 5% sodium carbonate solution to remove the acid. Wash the ether solution with water twice. Dry ether solution on sodium sulfate. Filter and evaporate ether. Recrystallize the solid from hot aqueous ethanol.
6.6 DERIVATIVES OF CARBOHYDRATES (a) Osazones Carbohydrates bearing an aldehyde or keto group react with excess phenylhydrazine to produce osazones. In the formation of osazones one carbonyl group is oxidized, therefore, a number of isomeric sugars (of the type OCHCHOHR and CH2OHCOR, i.e., D-glucose, D-mannose and D-fructose) form osazones.
112
LABORATORY MANUAL OF ORGANIC CHEMISTRY
Procedure: In a test tube place 0.2 g sugar, 0.4 g phenylhydrazine, 0.6 g sodium acetate and 4 ml distilled water. Place the tube in a beaker of boiling water. Note the time of immersion and the time of precipitation of the osazone. Shake the tube occasionally. The time required for the precipitation of the osazone may be taken as evidence for the identification of the unknown sugar. The melting points of the osazones being too close are generally of no value. Table 6.1: Some physical properties of carbohydrates Sugar
Specific rotation in water at 20°C
Time for osazone formation (min)
m.p. of osazone (°C)
D-Glucose (hydrates)
+48
45
205
Pentaacetate, =-112, >-132
D-Glucose (anhydrous)
+53
45
205
Pentabenzoate, 179
D-Fructose
92
2
205
Pentaacetate =-70, >-109 Pentabenzoate, 79
Maltose (hydrated)
+129
Soluble
Maltose (anhydrous)
+129
Soluble
Octaacetate, =-125, =-169
D-Galactose (anhydrous)
+82
15
Lactose (anhydrous)
+52
Soluble
Sucrose
+66
30
205
Octaacetate, 69
L-Arabinose
+105
9
166
Pentaacetate, =-94, >-86
D-Xylose
+19
7
164
Pentaacetate, =-59, >-126
201
Derivatives (°C)
Question 6.5 Why is it easy to isolate an osazone than a sugar itself?
PREPARATION OF DERIVATIVES
113
(b) Acetates A carbohydrate need to be completely acetylated in order to avoid any contamination. For this purpose an excess of the acetylating agent, i.e., acetic anhydride is used. The = - or the > - form of the acetate may be obtained depending on the catalyst employed.
>-Acetate Procedure: Dissolve 1 g of powdered unknown carbohydrate and 1 g of powdered fused sodium acetate in 10 ml of acetic anhydride by warming under reflux in a round-bottomed flask. The dissolution may take 30-35 min. After a clear solution is obtained heat for a further period of 2 hr. Pour the hot reaction mixture carefully into 50 ml of ice-cold water with stirring. Stir vigorously with a glass rod to decompose the excess acetic anhydride. Filter the solid and wash with cold water. Recrystallize from hot ethanol.
=-Acetate >-Acetate may be converted into =-acetate as follows: Procedure: Dissolve 0.5 g of the >-acetate in 2.5 ml 2% anhyd. zinc chloride in acetic anhydride in a 100 ml round-bottomed flask. Reflux the mixture on a water-bath for 30 min. Cool and pour the contents into 25 ml ice-cold water and stir vigorously. Filter the solid and wash with cold water. Recrystallize from hot ethanol.
(c) Benzoates Crystalline benzoate derivatives of glucose and fructose are prepared using benzoyl chloride. Procedure: The properties of carbohydrates are listed in table 6.1. In a 100 ml Erlenmeyer flask, dissolve 0.5 g glucose in 5 ml water. To this solution add 15 ml of 10% sodium hydroxide solution and 1 ml of benzoyl chloride. Stopper the flask and shake until the odor of benzoyl chloride has disappeared and a crystalline solid has separated. Filter the solid and wash it with a small quantity of water. Recrystallize from hot ethanol.
114
LABORATORY MANUAL OF ORGANIC CHEMISTRY
6.7 DERIVATIVES OF AMINES A. Primary and secondary amines (a) Benzamides The benzoylation of a primary or secondary amine is frequently achieved by the Schötten Baumann reaction.
This reaction should be performed in the hood. Procedure: In a boiling tube heat about 0.3 g (0.2 ml for liquid) of amine, 3 ml of 10% sodium hydroxide solution. To the mixture add 0.8 ml of benzoyl chloride slowly with vigorous shaking. Heat on a steam-bath for 15 min. Cool and add an excess of 10% sodium hydroxide solution to make the solution alkaline. Collect the solid and recrystallize from hot aqueous ethanol.
Question 6.6 Why do tertiary amines fail to react in this reaction?
(b) p-Toluenesulfonamides p-Toluenesulfonyl chloride reacts with amines to form a p-toluene sulfonamide.
Procedure: In a 50 ml round-bottomed flask reflux a mixture of 0.5 ml (0.5 g ) amine and 0.75 ml of p-toluenesulfonyl chloride in 4 ml of pyridine for 30 min. Pour the hot solution in 25 ml of 5% hydrochloric acid taken into a beaker. Stir the mixture well with a glass rod till solid crystallizes out. Filter the solid and wash with 10 ml water. Recrystallize from aqueous ethanol.
115
PREPARATION OF DERIVATIVES
B. Tertiary amines Picrates are frequently employed as derivatives of the tertiary amines using picric acid. Picrates are colored solids.
Procedure: In a test tube dissolve 1 g of the amine in a minimum amount of ethanol and add a solution of 0.5 g of picric acid also dissolved in a minimum amount of ethanol. Heat on a water-bath at 80°C for 510 min and shake occasionally. Cool and pour the contents onto ice water. Collect the solid, wash thoroughly with water and recrystallize from hot ethanol.
6.8 DERIVATIVES OF HYDROCARBONS (a) Picrates A large number of hydrocarbons also react with picric acid to form addition products, called picrates and are useful in the identification of aromatic hydrocarbons. Procedure: Dissolve equimolar quantities of the hydrocarbon (1 g anthracene ) and picric acid (1.6 g) in two separate test tubes in 3 ml of boiling benzene or ethanol. Mix the solutions while hot and heat at 50 to 60°C for 5 min. Allow the mixture to cool. Filter the picrate and wash with ice cold benzene or ethanol. Determine the melting points. Naphthalene
150°C (Yellow)
Anthracene
142°C (Red)
Phenanthrene
145°C (Yellow)
Acenaphthene
162°C (Orange )
Benzene forms only a labile picrate.
(b) 1, 3, 5 - Trinitrobenzene adducts Procedure: Dissolve 0.2 g of the aromatic hydrocarbon in 1 ml ethanol. To this add 0.2 g of 1, 3, 5-trinitrobenzene dissolved in 2 ml of cold ethanol. Cool the mixture in ice till precipitate forms. Filter and recrystallize the solid from ethanol.
116
LABORATORY MANUAL OF ORGANIC CHEMISTRY
6.9 DERIVATIVES OF ALKENES AND ALKYNES Both the unsaturated alkenes and alkynes may be characterized by preparing their adducts with 2, 4-dinitrobenzenesulfenyl chloride. This reagent adds to the CC unsaturated bonds to form crystalline derivatives.
Preparation of derivative for Alkenes Procedure: In a test tube, take 0.2 g of 2, 4-dinitrobenzenesulfenyl chloride and 0.3 g of the unknown alkene in 2.5 ml of glacial acetic acid. Heat the solution for 15 min on a steam-bath. Cool and pour onto crushed ice taken in a beaker and stir with a glass rod till a solid is obtained. Filter the crude solid and recrystallize from ethanol.
Preparation of derivative for Alkynes Procedure: In a 50 ml Erlenmeyer flask, dissolve 1.5 g of 2, 4-dinitrobenzenesulfenyl chloride in 1.2 ml of 1,1-dichloroethane. Cool the solution in ice for 15 mn. Add 3 ml of the unknown alkyne, shake and allow the mixture to stand at 0°C for 2 hr or until a solid is obtained. Filter the crude solid and recrystallize from ethanol. Note if the crude product is dark in color, decolorize it with activated charcoal.
6.10 PHYSICAL CONSTANTS To establish the identity of the unknown and its derivative the physical constants are determined and the values compared with the known data. We are here concerned mainly
PREPARATION OF DERIVATIVES
117
with the melting and boiling points. Both these constants particularly the melting point represent important criteria for purity of the substance.
6.10.1 Melting Point The melting point of a compound may be described as the temperature at which the solid and the liquid phases exist in equilibrium. In ideal cases if heat is provided to a crystalline
solid no rise in temperature should take place till all the solid has melted (melting point) . Conversely, if heat is removed from such a mixture, the temperature will not drop until all
the liquid has been converted to solid (freezing point). Therefore, the melting and freezing points of a pure substance should be identical. A number of physical properties such as color, odor, crystalline state, refractive index, specific rotation are measured in order to identify an unknown organic compound. Melting point and boiling point, however, are the most frequently determined physical data. For solid substances the most important characteristic is the melting point. It can be determined in the laboratory rapidly and most accurately using simple apparatus and moreover, by using only small quantities of the unknown sample. Furthermore, it furnishes valuable information regarding the identity and purity of the compound under examination. If the substance is completely pure and dry it will have a sharp melting point which is not raised by further purification. As a matter of fact this is also a conventionally accepted criterion for purification. But most apparatus employed for the measurement of melting point are designed for the ease of use rather than accurate determination. In practice, therefore, a melting point range is actually measured rather than a sharp melting point of the substance. If a substance is relatively pure, its melting point range is narrow and the top of the range is very near to the accurate melting point. Is contrast, if a substance is impure then it will have a broad range and moreover, the top of the range is lower than that of the true melting point. In other words, the purification of an impure substance may be accomplished by the determination of the melting point and when this becomes sharp and attains a constant value, the substance is considered pure. It is important to point out here that the range of melting point be reported if a sharp melting point is not observable. The melting range of a compound determined for many compounds may be between 1-2°C. A pure substance will melt in a narrow melting range. Furthermore, suppose the melting point of an unknown compound is determined to be 122°C. A literature survey reveals that there may be several compounds which have a melting point of 122°C. Therefore to, decide the identity of the unknown compound, a small sample of the unknown compound is mixed with a small quantity of the compound from the bottle and the melting point of the mixture popularly known as the mixed melting point is determined. If these two compounds are same then the mixture will melt at the same temperature as each compound does separately. On the other hand, if the compounds are different, the melting point of the mixture will be lower and also have a broad range.
118
LABORATORY MANUAL OF ORGANIC CHEMISTRY
Procedure: A small amount (0.1-0.2 g) of the compound (benzoic acid or urea) is first powdered with a spatula on a porous plate using a glass rod. The substance is then introduced
into a capillary tube ( 5 cm long) to pack it to a height of 3 mm. The capillary is now attached to a thermometer by means of a small rubber band. Note that the top of the thermometer and the capillary tube are at the same level. The thermometer along with the tube is now immersed in a heating bath. A Thiele tube or a Kjeldahls flask with an appropriate liquid may be used. A Thiele tube clamped on iron-stand containing liquid paraffin or conc. sulphuric acid is shown in Fig. 6.1. Heat the bath slowly. The temperature at which the compound commences to liquefy and at which it is completely liquid is recorded as the melting point range. A number of commercially available apparatus are available nowadays. The one shown in Fig. 6.2 requires no liquid and heating is done electrically. Such systems give more reliable melting points.
Fig. 6.1: Assembly for the determination of melting point.
119
PREPARATION OF DERIVATIVES
Fig. 6.2: A melting point block.
Questions 6.7 The sample for the determination of melting point should not be powdered on the filter paper. Why? 6.8 Would a pure compound always give a sharp melting point? 6.9 What does a mixed melting point determination indicate?
6.10.2 Boiling Point The boiling point of a pure liquid is defined as the temperature at which the pressure on the liquid equals the vapor pressure. The observed boiling point is directly proportional to the pressure. As the temperature rises the vapor pressure rises. It is necessary to state the pressure also while writing the b.p., for instance, b.p. 165°C/700 mm. The standard boiling point is typically measured at atmospheric pressure, i.e., 760 mm of Hg. Presence of impurities similar to melting point influence the boiling point of a liquid and it depends on the nature of the impurity A non-volatile impurity may generally lead to sharp boiling point, whereas volatile impurities raise the boiling point. Polar liquids often boil higher them non-polar liquids of the same molecular weight. Associated liquids boil still higher then unassociated ones. A determination of boiling point is useful for the identification of a
120
LABORATORY MANUAL OF ORGANIC CHEMISTRY
pure liquid. A liquid as a rule, will boil at a constant temperature provided the pressure remains constant. Because of its dependence on pressure and its erratic response to impurities the boiling point is generally less reliable than is the m.p. of solids. However, most mixture of liquid boil over a fairly wide temperature range even at constant temperature.
Fig. 6.3: Assembly for the determination of boiling point.
A mixture of two different substances of the same melting point will show a melting point below that of each pure substance of the mixture. In contrast, a mixture of two liquids of the same boiling point will have the same boiling point as each individual one. Thus the boiling point is less useful for identification than the melting point. Boiling point can be determined in an apparatus shown in Fig. 6.3. Procedure : Place 3-4 drops of the liquid whose boiling point is to be determined in an ignition tube. Immerse a capillary tube sealed at the other end in the liquid (if the liquid
rises in the tube in means that it is not properly sealed). Attach the ignition tube to a thermometer by means of a rubber band. Suspend the thermometer in a long-necked flask containing paraffin oil or in a Theile tube. Heat the flask uniformly with a burner, until a rapid stream of bubbles starts coming out of the capillary tube (because the air inside the
tube warms and expands) . At this point remove the burner and permit the flask to cool. The steam of bubbles become slower and the temperature drops until a point is reached
PREPARATION OF DERIVATIVES
121
when the bubbling ceases, and the liquid commences to rise in the capillary tube. This is the boiling point of the liquid.
Question 6.10 If two miscible liquids are found to boil at exactly the same temperature, could the conclusion be drawn that they are identical?
6.11 SEPARATION OF BINARY MIXTURES At some stage during a laboratory course in organic qualitative analysis, the student would be required to separate and identify the components of a mixture of organic compounds. A successful characterization depends on a wise separation of the mixture into sufficiently pure state to permit correct identification. The separation is based on the difference in some physical properties of the components at the time of separation. The important property that we are often concerned with is the difference in solubilities of the constituents in different solvents. In other words, with the experiment involving a separation by extraction procedure. In complicated cases, techniques like fractional distillation or fractional recrystallization may be employed. The first step is a visual inspection; in case two layers or phases are observed, they should be separated by mechanical means, i.e., a simple filtration or use of a separatory funnel. The separation is facilitated by determining the acid-base character of the mixture. This information, however, may not be reliable with regard to the composition of the mixture. Then separation may be attempted by using any one of the following solvents: (a) Cold water (b) Hot water (c) Hydrochloric acid (10%) (d) Sodium bicarbonate (10%) (e) Sodium hydroxide (10%) (f) Organic solvents. The choice of a solvent may be narrowed down by making an elemental analysis on the mixture. For instance, if nitrogen is absent, then there is no need to use hydrochloric acid for dissolution. If an acid is found to be a successful reagent, then the basic component can be recovered from the solution by neutralizing it with a base, on the other band, if it dissolves in sodium bicarbonate solution then the acid from the sodium salt is regenerated by acidifying with hydrochloric acid. In short, an acid is regenerated by using an acid and a base is regenerated by neutralizing the solution with a base. A brief discussion for the separation of several binary mixtures will illustrate the application of the general procedure involved.
122
LABORATORY MANUAL OF ORGANIC CHEMISTRY
(a) Aniline and m-nitrotoluene None of these is soluble in water but both are soluble in ether. An elemental analysis shows the presence of nitrogen and the mixture is basic to litmus. The addition of 10% hydrochloric acid would convert aniline into its salt but will not affect m-nitrotoluene. The latter compound can thus be separated by extraction of the mixture with ether. The aqueous solution is basified with 10% sodium hydroxide solution to obtain aniline.
(b) Bezophenone and benzoic acid None of these is soluble in water but both dissolve in ether. Nitrogen is absent and the mixture is acidic to litmus. Therefore, shake the mixture with 10% sodium hydroxide solution. Benzoic acid would dissolve as its sodium salt but benzophenone would be insoluble. Benzophenone can be obtained by extraction of the mixture with ether. The acid by acidifying the aqueous solution with 10% hydrochloric acid.
(c) Salicylic acid and succinic acid Both these substances are polar and soluble in water. Succinic acid, however, is not expected
to be appreciably soluble in ether because of its higher polarity (two carboxyl groups) . The components can thus be separated by extraction of benzoic acid with ether. Several additional example of binary mixtures and the solvents suggested for their separation are listed below: Table 6.2: Suggested solution for some mixture dissolution Mixture
Suggested Solvents
Benzoic acid + anthracene
Dil. sodium bicarbonate
=-Naphthol + naphthalene
Dil. sodium hydroxide
Urea + phenyl benzoate
Water
p-Toluidine + benzophenone
Dil. hydrochloric acid
p-Nitroaniline + succinic acid
Water
p-Nitrotoluence + benzamide
Hot water
p-Chlorobenzoic acid + benzophenone
Dil. sodium bicarbonate
Aniline + acetophenone
Dil. hydrochloric acid
Mannitol + =-naphthol
Water
Urea + iodoform
Ether
Sucrose + salicylaldehyde
Ether
Table 6.3: Alcohols and Phenols Derivatives Compound
(1)
m.p. (°C)
b.p. (°C)
Solubility Water
3-5-Dinitrobenzoates
F-Nitrobenzoates
m.p. (°C)
m.p. (°C)
(2)
(3)
(4)
(5)
(6)
n-Propyl alcohol
97
Sol
75
35
tert-Butyl alcohol
25
83
Sol
142
116
o-Cresol
30
191
Sol
138
94
p-Cresol
26
202
Sol
189
98
Phenol
43
182
Sol
146
126
p-Chlorophenol
43
217
186
158
o-Nitrophenol
45
216
155
141
p-Ethylphenol
47
130
81
Thymol
51
103
70
p-Methoxyphenol
55
p-Bromophenol
64
191
180
Benzhydrol
68
141
=-Naphthol
94
217
Hot water
Hot water
235
143
Acetates m.p. (°C)
Benzoates m.p. (°C)
(7)
(8)
PREPARATION OF DERIVATIVES
6.12 PHYSICAL CONSTANTS OF SOME COMMON ORGANIC COMPOUNDS AND THEIR DERIVATIVES
69
42 60
56
123
(Contd...)
(2)
m-Nitrophenol
97
(3)
(4)
(5)
(6)
(7)
159
174
56 63
Catechol
105
Sol
152
169
Resorcinol
110
Sol
201
182
d-Sorbitol
110
Sol
p-Nitrophenol
114
Hot water
2,4-Dinitrophenol
114
Picric acid
122
99 186
Sol
159
83
143
76
(8)
124
(1)
129
Benzene picrate m.p.84°C >-Naphthol
123
Insol
186
169
Pyrogallol
133
Sol
205
230
Mannitol
166
Sol
Hydroquinone
170
Sol
70 149 121
263
143
115
o-Chlorophenol
176
o-Bromophenol
195
m-Cresol
202
165
90
m-Chlorophenol
214
159
99
m-Bromophenol
236
LABORATORY MANUAL OF ORGANIC CHEMISTRY
317
Derivatives Compound
(1)
m.p. (°C)
b.p. (°C)
Solubility Water
Amides m.p. (°C)
F-Toluides m.p. (°C)
I-Benzoylisothiouronium salts m.p. (°C)
F-Bromophenyl esters m.p. (°C)
(2)
(3)
(4)
(5)
(6)
(7)
(8)
95
165
89
268
198
242
143
144
146
118
Acetoacetic acid
37
54
2-Phenylbutanoic acid
42
85
Bromoacetic acid
50
91
91
Chloroacetic acid
63
118
162
Cyanoacetic acid
66
120
Phenylacetic acid
76
Glycolic acid
79
120
Iodoacetic acid
83
95
Phenoxyacetic acid
99
102
Hot water
157
100
Sol
Oxalic acid
101
Sol
o-Toluic acid
105
Sp. sol
m-Toluic acid
112
95
4-Phenylbenzoic acid
113
131
2-Acetylbenzoic acid
115
116
Benzoic acid
121
Hot water
215
129
143
189
158
167
119
(Contd...)
125
Citric acid
PREPARATION OF DERIVATIVES
Table 6.4: Carboxylic Acids
(2)
(3)
(4)
(5)
(6)
(7)
(8)
3-Furoic acid
121
169
o-Benzylbenzoic acid
127
165
Cinnamic acid
133
2-Furoic acid
133
Acetylsalicylic acid
135
Hot water
138
Phenylpropiolic acid
136
Insoluble
109
142
m-Nitrobenzoic acid
140
143
162
o-Chlorobenzoic acid
141
p-Chlorobenzoic acid
142
Anthranilic acid
146
Sol
109
149
172
o-Nitrobenzoic acid
147
Hot water
175
109
107
o-Bromobenzoic acid
150
Sp. sol
155
171
Benzilic acid
150
Adipic acid
152
2, 5-Dichlorobenzoic acid
153
m-Bromobenzoic acid
155
m-Chlorobenzoic acid
158
Salicylic acid
158
1-Naphthoic acid
162
205
o-lodobenzoic acid
162
110
Sp. Sol
141 143
Hot water
108
107 131
190
220
163
165
168
126
148
140
155 Sol
155 134
Sol
139
156
(Contd...)
LABORATORY MANUAL OF ORGANIC CHEMISTRY
154 Sol
256
141 142
126
(1)
(2)
(3)
(4)
(5)
2, 4-Dichlorobenzoic acid
164
194
d-Tartaric acid
170
196
m-Aminobenzoic acid
174
111
p-Toluic acid
178
2, 4-Dinitrobenzoic acid
183
Anisic acid
184
2-Naphthoic acid
185
Succinic acid
186
m-lodobenzoic acid
187
p-Aminobenzoic acid
188
Coumarin-1-carboxylic acid
188
Phthalic acid
195
L-Tartaric acid
204
226
3, 4-Dihydroxybenzoic acid
209
268
2, 4-Dihydroxybenzoic acid
213
222
4-Hydroxybenzoic acid
215
162
4-Phenylbenzoic acid
226
223
p-Nitrobenzoic acid
241
Sp. sol
179
p-Chlorobenzoic acid
236
Sp. sol
201
p-Bromobenzoic acid
251
Hot water
159
(6)
(7)
(8)
160
190
153
154
211
158
154
182
136
203 Sp. sol
162 192
Sol
PREPARATION OF DERIVATIVES
(1)
192
260 186
Hot water
114 236
Hot water
220
127
190
204
128
Table 6.5: Aldehydes Derivatives Compound
(1)
m.p. (°C)
b.p. (°C)
Solubility (water)
Phenylhydrazones m.p. (°C)
2, 4-Dinitrophenylhydrazones m.p. (°C)
Semicarbazones m.p. (°C)
(2)
(3)
(4)
(5)
(6)
(7)
34
Pipernal
37
o-Methoxybenzaldehyde
39
o-Aminobenzaldehyde
40
o-Nitrobenzaldehyde
44
Chloral hydrate
56
m-Nitrobenzaldehyde
221
221
266
234
254
215 247
137
265
256
58
293
246
2-Naphthaldehyde
60
270
245
3, 5-Dichlorobenzaldehyde
65
2, 4-Dichlorobenzaldehyde
74
p-Bromobenzaldehyde
67
p-Aminobenzaldehyde
72
126
173
Sol
113 Sol
n-Butyraldehyde
74
Chloral
96
Pentanal
156
131
103
(Contd...)
LABORATORY MANUAL OF ORGANIC CHEMISTRY
1-Naphthaldehyde
(2)
(3)
(4)
(5)
(6)
98
322
(7)
m-Hydroxybenzaldehyde
104
p-Nitrobenzaldehyde
106
p-Hydroxybenzaldehyde
116
Hexanal
131
230
106
Fufural
162
237
206
280 Sp sol
178
221
104
Benzaldehyde
179
Sp sol
158
252
Salicyladehyde
196
Sp sol
143
252
100
m-Methylbenzaldhyde
199
195
204
o-Methylbenzaldehyde
200
104
209
p-Methylbenzaldehyde
205
234
234
o-Chlorobenzaldehyde
213
86
209
p-Chlorobenzaldehyde
214
172
265
o-Bromobenzaldehyde
230
m-Methoxybenzaldehyde
230
233
m-Bromobenzaldehyde
234
228
p-Methoxybenzaldehyde
248
253
210
Cinnamaldehyde
252
255
216
PREPARATION OF DERIVATIVES
(1)
129
130
Table 6.6: Ketones Derivatives Compound
m.p. (°C)
b.p. (°C)
Solubility (water)
Phenylhydrazones m.p. (°C)
2, 4-Dinitrophenylhydrazones m.p. (°C)
Semicarbazones m.p. (°C)
(2)
(3)
(4)
(5)
(6)
(7)
Methyl ethyl ketone
80
Sol
115
146
2-Butanone
82
117
136
Cyclobutanone
100
146
Diethylacetone
102
3-Pentanone
(1)
Sol
139
102
156
179
2-Pentanone
102
144
112
Pinacolone
106
125
158
Chloroacetone
119
125
150
3-Hexanone
125
170
113
2-Hexanone
128
100
Cyclopentanone
131
206
3-Heptanone
148
2-Heptanone
151
164 103
89
123
(Contd...)
LABORATORY MANUAL OF ORGANIC CHEMISTRY
156
(2)
Cyclohexanone
(3)
(4)
155
Sol
Benzoquinone
115
Insol
Benzophenone
49
Insol Insol
(5)
(6)
(7)
160
166 243
238
Acetophenone
202
105
250
Menthone
209
146
189
Propiophenone
220
191
174
Butyrophenone
222
163
181
d-Carvone
230
190
188
p-Chloroacetophenone
232
231
204
o-Methoxyacetophenone
239
183
m-Methoxyacetophenone
240
196
n-Velerophenone
248
166
PREPARATION OF DERIVATIVES
(1)
160
131
132
Table 6.7: Esters Compound (1)
m.p. (°C)
b.p. (°C)
3, 5-Dinitrobenzoate m.p. (°C)
(2)
(3)
(4)
18
Diethyl tartarate
18
Benzyl benzoate
18
(+) Bornyl acetate
27
154
Methyl cinnamate
36
108
Elhyl mandelate
37
Phenyl salicylate
42
Dimethyl tartarate
49
Methyl mandelate
53
Dimethyl oxalate
45
Phenyl benzoate
69
93
2-Naphthyl acetate
71
210
Methyl p-nitrobenzoate
96
108
Ethyl formate
54
93
Methyl acetate
57
108
Ethyl acetate
77
108
Methyl propionate
80
108
iso-Propyl acetate
90
123
(Contd...)
LABORATORY MANUAL OF ORGANIC CHEMISTRY
Dimethyl succinate
(3)
(4)
tert-Butyl acetate
98
142
Methyl acrylate
80
108
Ethyl propionate
100
93
Propyl acetate
102
Methyl butyrate
102
Allyl acetate
104
Cholestryl acetate
(2)
114
Methyl crotonate Hydroquinone diacetate
119 124
Methyl pyruvate
137
Ethyl crotonate
138
Dimethyl terephthalate
PREPARATION OF DERIVATIVES
(1)
141
93
Ethyl chloroacetate
145
Ethyl pyruvate
155
Methyl acetoacetate
170
Cyclohexyl acetate
172
Furfuyl acetate
176
Ethyl acetoacetate
181
Diethyl oxalate
185
Dimethyl succinate
196
58
93
133
(Contd...)
(2)
(4)
Phenyl acetate
197
146
Diethyl malonate
199
93
Methyl benzoate
199
108
C-Butyrolactone
204
Ethyl benzoate
212
93
Benzyl acetate
217
113
Diethyl succinate
218
206
Methyl phenylacetate
220
108
Methyl salicylate
224
Ethyl phenylacetate
228
93
Propyl benzoate
231
74
Ethyl salicylate
234
Diethyl adipate
245
Ethyl cinnamate
271
Diethyl tartarate
280
Dimethyl phthalate
284
Diethyl phthalate
290
Diisobutyl phthalate
327
Dibutyl phthalate
340
93
108
LABORATORY MANUAL OF ORGANIC CHEMISTRY
(3)
134
(1)
Derivatives Compound
m.p. (°C)
b.p. (°C)
Solubility (water)
Acetyl m.p. (°C)
Benzoyl m.p. (°C)
Picrates m.p. (°C)
F-Toluene sulfonamides m.p. (°C)
(2)
(3)
(4)
(5)
(6)
(7)
(8)
Ethylamine
17
Sol
165
63
Ethylmethylamine
36
Sol
135
52
56
Sol
155
55
77
Sol
151
90
Sol
173
229
Insol
(1)
N-Benzylamine
37
2, 6-Dichloroaniline
39
Propylamine
48
Indole
52
Diethylamine 8-Hydroxyquinoline
75
n-Butylamine Pyrrolidine
PREPARATION OF DERIVATIVES
Table 6.8: Amines
75
Triethylamine 2, 4-Diaminotoluene
99
o-Bromoaniline
32
p-Toluidine
45
99
116
90
154
158
118
135
(Contd...)
(2)
(3)
(4)
(5)
(6)
160
161
(7)
(8)
=-Naphthylamine
50
Diphenylamine
54
Insol
167
204
180
p-Bromoaniline
66
Hot water
179
193
178
p-Chloroaniline
71
Hot water
179
193
178
a-Nitroaniline
71
94
98
73
142
152
96
195
133
143
138
o-Phenylenediamine
106
>-Naphthylamine
113
m-Nitroaniline
114
Hot water
116
Pyridine
116
p-Aminophenol
123
Triphenylamine
127
2-Picoline
162
167 Sol
151
234
110
129 131
Cyclohexylamine
2-Aminoethanol
134
690 134
147
110 171
(Contd...)
LABORATORY MANUAL OF ORGANIC CHEMISTRY
Ethylenediamine
p-Nitroaniline
157
102
Piperidine
Pyrole
136
(1)
(2)
o-Hydroxyaniline
174
o-Aminophenol
174
m-Aminoaniline
180
(3)
(4)
(5)
(6)
Sp sol
124
184
(7)
139
Benzyldimethylamine
181
Aniline
184
198 d
N, N-Dimethylaniline
193
163
Dimethylamine
193
p-Aminophenol
(8)
103
PREPARATION OF DERIVATIVES
(1)
184
2, 4, 6-Trinitroaniline
190
o-Toluidine
200
65
Sol
112
143
60
105
124
Benzylamine
185
o-Chloroaniline
207
88
o-Ansidine
218
84
2-Methoxyaniline
225
200
Quinoline
237
203
p-Ansidine
51
246
130
o-Bromoaniline
31
250
99
251
Dibenzylamine
300
116
134
105
64
127
153
136
114 129
90
137
m-Bromoaniline
199
138
Table 6.9: Amides Derivatives Compound
m.p. (°C)
Picrates b.p. (°C)
Acids m.p. (°C)
(2)
(3)
(4)
N-Methylacetamide
31
30
Methyl urethane
52
Phenyl urethane
53
Acetoacetamide
60
Caprolactam
71
Propionamide
81
141
Acetamide
82
118
Acrylamide
85
140
o-Nitroacetanilide
92
Maleimide
93
130
m-Toluamide
97
112
Pentanamide
106
186
Acetanilide
114
216
Butanamide
115
164
Succinimide
126
iso-Butyramide
129
Benzamide
130
m-Chlorobenzamide
134
Phenecetin
134
Salicylamide
142
158
o-Toluamide
143
104
(1)
37
155 121
(Contd...)
LABORATORY MANUAL OF ORGANIC CHEMISTRY
189
(2)
(3)
m-Nitrobenzamide
143
140
Cinnamide
148
133
m-Bromobenzamide
155
155
Phenylacetamide
156
76
p-Toluamide
159
179
o-Bromobenzamide
161
150
p-Hydroxybenzamide
162
215
Benzanilide
169
p-Bromosuccinimide
167
p-Methoxybenzamide
167
m-Hydroxybenzamide
170
N-Bromosuccinimide
173
o-Nitrobenzamide
176
146
p-Chloroacetanilide
179
243
p-Aminobenzamide
183
188
3, 5-Dinitrobenzamide
183
207
p-Bromobenzamide
189
251
p-Nitrobenzamide
200
241
1-Naphthamide
202
182
2, 6-Dichlorobenzamide
202
144
2, 4-Dinitrobenzamide
203
183
Phthalimide
238
210
Succinamide
260 dec
189
(4)
PREPARATION OF DERIVATIVES
(1)
204 185
200
139
140
Table 6.10: Hydrocarbons Compound
m.p. (°C)
b.p. (°C)
Solubility (water)
Nitro derivatives m.p. (°C)
Picrates m.p. (°C)
(2)
(3)
(4)
(5)
(6)
Diphenylmethane
26
262
Insol
172 (2, 2, 4, 4)
1, 2-Diphenylethane
53
284
Insol
180 (2, 4)
Pentamethylbenzene
54
232
Insol
154 (6)
Diphenyl
69
234 (4, 4)
Naphthalene
80
81 (1)
(1)
Benzene
80
89 (1, 3)
84
92
206 (4, 4, 4)
Acenaphthene
96
101 (5)
161
Phenanthrene
100
144
143
70 (2, 4)
88
Toluene
111
Fluorene
114
156 (2)
Unstable
trans-Stilbene
124
120 (1, 3, 5)
Unstable
p-Xylene
138
139 (2, 3, 5)
Unstable
m-Xylene
139
182 (2, 4, 5)
o-Xylene
144
71 (4, 5)
Anthracene
216
138 (unstable)
LABORATORY MANUAL OF ORGANIC CHEMISTRY
Triphenylmethane
PREPARATION OF DERIVATIVES
Table 6.11: Miscellaneous Compound (1)
m.p. (°C)
b.p. (°C)
(2)
(3)
m-Nitroanisole
38
Benzoic anhydride
42
o-Bromonitrobenzene
43
p-Dichlorobenzene
53
173
p-Nitrotoluene
54
238
Maleic anhydride
54
130
m-Chlorotoluene p-Bromobenzene
72 89
Acetanilide
114
Iodoform
119
Succinic anhydride
120
p-Nitrobromobenzene
127
Phthalic anhydride
132
o-Chloronitrobenzene
246
Phthaloyl chloride
280
Sulfanilic acid
288 dec
Aniline hydrochloride
198
141
(Contd...)
(2)
(3) 151
Anisole
155
o-Chlorotoluene
159
m-Chlorotoluene
162
p-Chlorotoluene
162
Phenetole
172
Benzyl chloride
180
o-Dichlorobenzene
180
o-Bromotoluene
182
p-Bromotoluene
184
Benzonitrile
190
Benzoyl chloride
197
2, 4-Dichlorotoluene
201
Phenacyl chloride
210
Nitrobenzene
211
o-Nitrotoluene
220
p-Chlorobenzyl chloride
222
m-Nitrotoluene
233
LABORATORY MANUAL OF ORGANIC CHEMISTRY
Bromoform
142
(1)
Chapter
7
ESTIMATION OF FUNCTIONAL GROUPS
Qualitative organic analysis has been the subject of the preceding chapters, for the identification of organic compounds. It is intended to discuss and perform some experiments of quantitative estimation of functional groups. In these exercise utmost care is needed for accurate working and measurement of correct data. For the preparation of standard solutions, the amounts stated within parenthesis represent the number in g/l of the solution.
7.1 ESTIMATION OF THE NUMBER OF HYDROXYL (–OH) GROUPS IN ALCOHOLS The number of hydroxyl groups in an alcohol or phenol can be estimated by acetylation with acetic anhydride. A known weight of the alcohol is acetylated with freshly distilled acetic anhydride in the presence of dry pyridine and is used in excess. At the end of the reaction excess of the anhydride is hydrolysed with water. Acetic acid so produced is titrated against standard alkali solution in order to determine the amount of the unreacted acetic anhydride.
Chemicals Acetic anhydride distilled. Ethanolic sodium hydroxide solution (0.5 N, 20 g/l). Dry pyridine (pyridine can be dried over potassium hydroxide pellets).
144
LABORATORY MANUAL OF ORGANIC CHEMISTRY
Procedure: First prepare the acetylating mixture by mixing one volume (11.5 g) of acetic anhydride and three volumes (34.5 ml) of dry pyridine in a clean Erlenmeyer flask. Fill a clean dry burette with this mixture and cork it. For the preparation of alcoholic sodium hydroxide solution. Prepare a saturated solution of sodium hydroxide in distilled water in a corked Erlenmeyer flask. Take 14 ml of this solution in a 500 ml volumetric flask and fill it if with ethyl alcohol. Standardize this solution with 0.5 N hydrochloric acid or sulfuric acid or preferably oxalic acid using phenolphthalein indicator. In a 250 ml Erlenmeyer flask equipped with a water condenser, weigh accurately (by transference method) 11.3 g sample (phenol, n-hexanol, cyclohexanol, or benzyl alcohol) and to this add 9 ml acetylating mixture from the burette (use double the amount if the alcohol is dihydric). Shake and reflux the contents on a water-bath for 45 min after replacing the condenser. Remove the flask and add 20 ml distilled water through the condenser and shake to ensure complete hydrolysis of the remaining acetic anhydride. Cool the flask and titrate the contents ( Note I ) against standard sodium hydroxide solution using phenolphthalein as indicator. Carry out a blank control experiment simultaneously using the above procedure with 9 ml of the acetylating mixture without adding alcohol or phenol. The difference in the volumes of sodium hydroxide solution required in the two experiments is equivalent to the difference in the amount of acetic acid formed, i.e., to the acetic acid derived from the acetic anhydride consumed in the actual acetylation of the sample. If the molecular weight of the alcohol is known, the number of OH groups in the alcohol can be determined. The advantage of control experiment is that the absolute concentration of the reagent (hence the exact concentration of acetic anhydride in pyridine) need not be determined. If the same volume of reagent is used in the actual and in the blank or control experiment, the difference gives the actual amount used.
Calculations Weight of the sample = W g Suppose the sample requires V ml and the blank requires V1 ml of 0.5 N sodium hydroxide solution. Difference = (V1 − V ) ml of 0.5 N NaOH or
(V1 − V ) ml of 1 N NaOH 2
1000 ml of 1 N NaOH = 1 g mol. wt. of NaOH = 1 g mol. wt. of acetic acid = 1 OH group/molecule of alcohol \
(V1 − V ) (V1 − V ) ml of 1 N NaOH = OH groups 1000 × 2 2
145
ESTIMATION OF FUNCTIONAL GROUPS
W g of the alcohol sample contains
(V1 − V ) OH groups 1000 × 2
94 g (assuming the sample to be phenol) contains
(V1 − V ) 94 × OH groups/molecule 1000 × 2 W Note I: For better results the sample after refluxing may be diluted to 100 ml in a measuring flask and 10 ml aliquot titrated against a dilute solution (0.1 N) of NaOH.
Question 7.1 What is the purpose of running a blank?
7.2 DETERMINATION OF THE PURITY OF PHENOL The purity of a phenol sample can be determined by bromination using potassium bromatebromide solution as the brominating reagent. Excess bromine is then titrated against standard sodium thiosulfate solution: KBrO3 + 5 KBr + 6 HCl
2 KI + Br 2 I2 + 2 Na2S2O3
6 KCl + 3 Br2 + 3 H2O
2 KBr + I2 Na2S4O6 + 2 NaI
Chemicals Potassium bromate-bromide solution ( 0.2 N). Sodium thiosulfate solution (0.1 N, 25 g/l). Potassium iodide solution (20%). Starch indicator. Procedure: Prepare the potassium bromate-bromide solution by dissolving 75 g potassium bromide and 5.67 g potassium bromate in water and make up the solution to 1 litre in a volumetric flask.
146
LABORATORY MANUAL OF ORGANIC CHEMISTRY
Weigh accurately about 0.250.3 g of phenol sample, dissolve in 5 ml of 10% sodium hydroxide solution and dilute the solution to 250 ml in a volumetric flask. In a 500 ml stoppered flask pipette 25 ml of this solution, 25 ml of potassium bromate-bromide solution and add 25 ml of water. Also add 5 ml of conc. hydrochloric acid and immediately stopper the flask. Shake thoroughly for one min and then allow to stand for 30 min with occasional swirling. Cool the flask in ice and add 10% potassium iodide solution, shake, replace the stopper and allow to stand again for 10 min. Titrate the free iodine against standard sodium thiosulfate solution using starch as indicator. Add the indicator near the end-point, appearance of blue color indicates the end-point. Carry out a blank experiment simultaneously using 25 ml of the potassium bromate-bromide solution and 25 ml of water but no sample, using the above procedure. The blank determination is used to determine the total quantity of bromine generated and also indeterminate losses of the reagent are indentical and thus do not affect the result.
Calculations Weight of phenol taken = W g Volume of 0.1 N Na2S2O3 used for the sample = V ml volume of 0.1 N Na2S2O3 used for blank = V1 ml Volume of 0.1 N Na2 S2O3 used for phenol = (V1 V) ml 1000 ml of 1 N Na2S2O3 solution = 1 g equivalent weight of Na 2S2O3 solution (V1 − V ) × 0 .1 g equiv. weight of Na2S2O3 solution 1000 (V − V ) 1 = Equivalent weight of bromine = 1 × 0.1 × mole of phenol (since according to 1000 6
(V1 V) ml 0.I N Na2S2O3 =
the reaction above, 6 g equivalent of bromine = 1 mole of phenol) (V1 − V ) 0 .1 × 94 × g of phenol (Mol. wt. of phenol = 94) 1000 6
W g of the sample contains 100 g of the sample contains
(V1 − V ) 0.1 × 94 × g of phenol 1000 6 (V1 − V ) 0.1 × 94 100 × × g of phenol, which is the percentage W 1000 6
of phenol in the sample or percentage purity of the phenol sample. The amount of pure phenol is determined in 100 g sample.
Question 7.2 How can monobromination of phenol be achieved?
147
ESTIMATION OF FUNCTIONAL GROUPS
7.3 DETERMINATION OF EQUIVALENT WEIGHT OF A CARBOXYLIC ACID The equivalent weight of a carboxylic acid may be described as the number of grams of the acid required to neutralize one litre of normal alkali. If the basicity of the acid is known, the molecular weight may be calculated. Following two methods are employed for the determination of equivalent weight.
7.3.1 Silver Salt Method (Gravimetric Method) The carboxylic acid is converted to its silver salt which is ignited and the metallic silver formed is weighed.
Chemicals Silver nitrate solution (10%) AgNO 3. Dilute ammonium hydroxide solution (10%).
Procedure: Suspend 0.51 g of a carboxylic acid ( benzoic, phenylacetic, succinic acid, etc.) in 20 ml of distilled water in a 200 ml breaker and slowly add dilute ammonium hydroxide solution. Stir the mixture till the acid dissolves. Expel excess ammonia by warming the breaker on a water-bath till neutral. Cool and add silver nitrate solution to the neutral warm solution while stirring (Note I) to completely precipitate the acid as its silver salt. Filter the solid and wash thoroughly with water, drain and dry the solid in a vacuum desiccator (Note II). Weigh accurately about 0.5 g of the dried salt in a weighed crucible.
Heat the crucible (Note III) on a Bunsen burner first gently and then red hot until all the silver salt has decomposed. Cool the crucible in a desiccator and then determine its weight. Heat again till a constant weight of the crucible and its contents is obtained. Determine the weight of metallic silver formed.
Calculations Weight of silver salt taken = W g Weight of silver after ignition = w g w g of silver is obtained from W g of silver salt 107.9 silver will be obtained from =
107.9 × W g of silver salt w
= Equivalent wt. of silver salt
148
LABORATORY MANUAL OF ORGANIC CHEMISTRY
Equivalent wt. of the acid = Equivalent wt. of silver salt Atomic wt. of Ag + The wt. of H replaced by Ag =
107.9 × W − 107.9 + 1. w
The molecular weight can be obtained by multiplying the basicity with the equivalent weight. Notes I: Check with a litmus paper. II: Silver salt is sensitive to light, drying therefore, should be conducted with minimum exposure to light (cover the flask with carbon paper). III: Heat the whole crucible first on the flame to constant weight.
7.3.2 Volumetric Method A known weight of the acid is dissolved in water (or aqueous ethanol) and then titrated against standard alkali solution. This will determine the neutralization equivalent (equivalent weight) of the acid. The molecular weight is obtained by multiplying it with the basicity, if it is given.
Chemicals Sodium hydroxide solution 0.2 N (8 g/l). Procedure: Weigh accurately 1.52 g of an acid in a 100 ml volumetric flask and dissolve
in water or use enough alcohol (Note I ) to dissolve it. Fill the flask to the attached mark. Pipette out 25 ml of this acid solution in an Erlenmeyer flask, add 2 drops of phenolphthalein indicator and titrate against standard sodium hydroxide solution to a pink end-point. Note the volume of sodium hydroxide solution consumed.
Calculations Weight of the acid taken = W g in 100 ml solution Assume 25 ml of the acid consumes V ml of 0.2 N NaOH 100 ml of the acid will consume =
100 × V of 0.2 N NaOH 25
= 100/25 × V × 1 / 5 N NaOH = 4 V/5 1 N NaOH 4/5 V ml of 1 N NaOH is equivalent to W g of the acid 1000 ml of 1 N NaOH is equivalent to =
100 × W × 5 g of acid. 4V
149
ESTIMATION OF FUNCTIONAL GROUPS
This is also the equivalent weight of the acid. To obtain the molecular weight multiply by basicity. Note I: Use only ethanol to dissolve benzoic acid.
7.4 DETERMINATION OF SAPONIFICATION EQUIVALENT OF AN ESTER Saponification equivalent of an ester is defined as the equivalent weight of an ester as determined by titration with a standard acid. The value is useful in determining the empirical formula of the ester.
Chemicals Alcoholic potassium hydroxide solution (0.5 N). Hydrochloric acid 0.5 N. Potassium hydroxide solution (2 g dissolved in 100 ml 95% ethanol). This solution need not be standardized. Procedure: First prepare a standard potassium hydroxide solution in ethanol. For this dissolve 2 g of potassium hydroxide pellets in 100 ml of 95% ethanol in an Erlenmeyer flask. Allow the solution to settle and then decant it in a volumetric flask. Standardize it with 0.5 N hydrochloric acid solution. Transfer 10 ml of potassium hydroxide solution by means of a pipette into a 50 ml glass-stoppered Erlenmeyer flask. Accurately weigh about 0.5 g of the ester (ethyl benzoate or benzyl acetate) into the flask and replace the stopper. Swirl the flask to mix the ester with potassium hydroxide solution. Reflux the contents of the flask for 3040 min. Wash down the condenser with 25 ml water and cool. Add 2 drops of phenolphthalein and titrate against 0.5 N or 0.25 N hydrochloric acid. Note the volume of the acid consumed. Also run a blank under similar conditions.
Calculations Weight of the ester taken = W g Saponification equivalent =
W × 1000 ml Normality × ( )alkali − (ml × Normality )acid
For an ester of a mono-basic acid the value is equal to the molecular weight whereas for a dibasic acid it will be one half the molecular weight.
150
LABORATORY MANUAL OF ORGANIC CHEMISTRY
Questions 7.3 Can one esterify a carboxylic acid in the presence of a base? 7.4 List some other methods of esterification of a carboxylic acid.
7.5 ESTIMATION OF A KETO
GROUP
Methyl ketones can be estimated by treating with excess standard iodine in an alkaline medium and then titrating the unreacted iodine with standard sodium thiosulfate solution.
Chemicals Iodine solution
0.1 N ( dissolve 20 g potassium iodide and 6.3 g iodine in 100 ml water and make it to 1000 ml in a volumetric flask)
Sodium thiosulfate solution
0.1 N (24.8 g/l)
Sodium hydroxide solution
1 N (40 g/l )
Sulfuric acid
1N
Procedure: In a 250 ml Erlenmeyer flask fitted with a ground glass stopper weigh accurately
0.20.25 g of a ketone (acetone, acetophenone, ethyl methyl ketone, etc.). To this add 30 ml of 1 N sodium hydroxide solution and shake for 10 min. From a burette run 50 ml of 0.1 N iodine solution with constant stirring. Shake thoroughly for 1015 min till yellow crystals of iodoform appear. Acidify the solution with sulfuric acid and titrate against standard sodium thiosulfate solution using starch indicator.
151
ESTIMATION OF FUNCTIONAL GROUPS
Calculations Weight of the ketone taken = W g Vol. of 0.1 N iodine solution added = 50 ml Vol. of 0.1 N Na 2S2O3 needed to react with excess iodine = V ml = volume of 0.1 N I2 unused Volume of iodine that reacted with the ketone = (50 V) ml. Now according to the above reaction sequence 3 moles of I2 = one mole of ketone = 120 g (assuming it to be acetophenone) 1 equivalent of I2 ≡ 1N I2 solution = M/2 I2 solution 6 equivalents of I 2 ≡ 3 MI2 solution ≡ 6000 ml of 1 N I2 solution
≡ (6000 × 10) ml of 0.1 N I2 solution. (6000 × 10) ml of 0.1 N I2 solution contains 120 g of the ketone (50 V) ml of 0.1 N I2 solution W g sample contains =
120 × (50 − V ) g of the ketone 6000 × 10
120 × (50 − V ) g of the ketone 6000 × 10
100 g sample contains =
120 × (50 − V ) × 100 g of the ketone W × 6000 × 10
This is the percentage purity of the ketone, as the amount of pure ketone is determined in 100 g sample.
7.6 ESTIMATION OF AN ALDEHYDE
GROUP
An aldehyde is treated with an excess of sodium bisulfite solution and the unused sodium bisulfite solution is determined idometrically.
152
LABORATORY MANUAL OF ORGANIC CHEMISTRY
Chemicals Iodine solution (0.1 N). Sodium bisulfite solution (12 g/l). Procedure: In a 250 ml Erlenmeyer flask weigh accurately 0.20.25 g of the aldehyde
(propionaldehyde, n-butyraldehyde, etc.) and dissolve in water (alcohol for water insoluble aldehydes). Add 50 ml of sodium bisulfite solution and shake the mixture vigorously. Then allow to stand for 20 min. Titrate the excess bisulfite solution against 0.1 N iodine solution using starch indicator. Note the end-point which will be the appearance of a blue color
(Note I). Also titrate 50 ml of sodium bisulfite solution against 0.1 N iodine solution as
blank.
Calculations Wt. of the aldehyde taken = W g Assume 50 ml of NaHSO3 solution requires V ml of 0.1 N I2 solution and excess NaHSO3 solution requires V1 ml of 0.1 N I2 solution. (V V1) ml of 0.1 N I2 solution is equal to the iodine equivalent to the aldehyde. 1000 ml of 1 N I 2 solution = M/2 equivalent of the aldehyde (M is the mol. wt. of the aldehyde) 1000 ml of 0.1 N I2 solution = M/20 equivalent of the aldehyde
(V V1) ml of 0.1 N I 2 solution
=
Percentage purity of the aldehyde =
(V − V1 ) × M / 20 equivalent of the aldehyde 1000 (V − V1 ) × M / 20 × 100 / W 1000
Note I: Considerable variations of and fading in end-point are experienced during titration. It is probably due to the reversibility of the reaction and instability of the sodium bisulfite adduct. The result may not be very accurate.
Question 7.5 Why is a sharp end-point not observed in the estimation of aldehydes?
153
ESTIMATION OF FUNCTIONAL GROUPS
7.7 ESTIMATION OF SULFUR (MESSENGER’S METHOD) IN THIOUREA Sulfur in an organic compound is estimated by the Messengers method. According to this procedure sulfur of the organic compound is converted into sufluric acid by heating with alkaline potassium permanganate solution. Sulfuric acid is then precipitated with barium chloride solution as barium sulfate which is then estimated gravimetrically. The following reactions pertain to the estimation of sulfur in thiourea:
H2SO4 + BaCI2
BaSO4 + 2 HCl
Chemicals Potassium permanganate solution (0.51 g solid) . Barium chloride solution (5% ). Sodium hydroxide solution (10%). Procedure: Place accurately weighed 0.150.25 g sample of thiourea in a 250 ml roundbottomed flask fitted with an air-condenser. To this add 50 ml of distilled water and 3 ml of 10% sodium hydroxide solution. Shake the contents thoroughly and subsequently add 0.51 g of potassium permanganate in small lots. Add a few pieces of boiling chips, replace the condenser and reflux for 4-5 hrs (Note I) on a sand-bath. After this duration, cool the contents to room temperature and add conc. hydrochloric acid (1015 ml) dropwise to the flask until the purple color of unreacted potassium permanganate is decolorized. Heat the flask again for 1015 min and filter the contents into a beaker. Wash the flask thoroughly and transfer washing on the filter paper. Concentrate the solution to about 50 ml on a burner. Add barium chloride solution dropwise with constant stirring in order to precipitate sulfuric acid produced to barium sulfate. Allow the beaker to stand undisturbed for 30 min. and filter the precipitate on a Whatman filter paper. Wash the precipitate with distilled water (Note II ). Fold the filter paper, place it in a weighed silicon crucible and heat on a Bunsen burner to form ash. Cool the crucible in a desiccator and weigh it again. Determine the weight of barium sulfate precipitate.
Calculations Weight of thiourea taken = W g Weight of barium sulfate precipitate = w g According to the above reaction = 233.4 g of BaSO4 contains 32 g of S Therefore, w g of BaSO 4 =
32 × M g of 5 233 .4
154
LABORATORY MANUAL OF ORGANIC CHEMISTRY
W g sample of thiourea contains =
32 × M g of S 233.4
Percentage of sulfur in thiourea =
w 32 × × 100 233.4 W
Notes I: If the color of potassium permanganate disappears during heating, add more of it. II: Wash till chloride ions are removed. Check the filtrate with silver nitrate solution.
Question 7.6 Why does the purple color disappear on adding hydrochloric acid?
7.8 ESTIMATION OF NITROGEN (KJELDAHL METHOD) The nitrogen containing compound is digested with conc. sulfuric acid in the presence of a catalyst and nitrogen of the sample evolved is converted into ammonium sulfate. Then an excess sodium hydroxide solution is added and ammonia is steam distilled and absorbed in excess standard sulfuric acid solution. The remaining mineral acid is back-titrated against standard sodium hydroxide solution which gives the equivalent of the ammonia obtained from the weight of sample taken. The following reactions involved are illustrated by reference to glycine:
(NH4)2SO4 + 2 NaOH 2 NH3 + H2SO4
2 NH3 + Na2SO4 + 2 H2O
(H4)2SO4
Chemicals Sulfuric acid solution (0.1 N). Sodium hydroxide solution (0.1 N, 4 g/l). Catalyst [a mixture of K 2SO4 (20 g), selenium powder (1 g ) and CuSO4. 5H2O (1 g)] Procedure: Weigh accurately 0.120.2 g of the substance (benzamide, diphenylamine, acetanilide, etc.) in a clean 50 ml Kjeldahl flask. Add 1.0 g of the catalyst and 5 ml of conc. sulfuric acid. Potassium sulfate serves to elevate the boiling point of sulfuric acid while others act as catalyst. Stopper the flask loosely and digest on a sand-bath as shown in Fig. 7.1 in a slightly inclined position for 23 hrs (Note I ) in a hood. After the digestion is complete, cool the
ESTIMATION OF FUNCTIONAL GROUPS
155
flask. In the meantime set up the distillation apparatus as depicted in Fig. 7.2 ( Note II) Transfer the mixture from the Kjeldahl flask into the chamber C. Pass steam into the outer chamber B by turning the stopcock A. Introduce carefully 40 ml of 50% sodium hydroxide solution through the funnel E. Take 50 ml of standard sufuric acid in an Erlenmeyer flask G. Continue to pass steam for 5060 min. to ensure that all the ammonia evolved has been absorbed by the acid. Turn off the stopcock A to cut off the flow of steam. Excess water can be removed from the outlet H.
Fig. 7.1: Kjeldahl flask heated on a sand-bath.
Fig. 7.2: Steam distillation and absorption of ammonia.
The excess of the acid in the Erlenmeyer flask ( G) may be titrated against standard sodium hydroxide solution, using phenolphthalein indicator.
156
LABORATORY MANUAL OF ORGANIC CHEMISTRY
Calculations Weight of the nitrogenous compound taken = W g Volume of 0.1 N H2 SO 4 taken = 50 ml Volume of 0.1 N NaOH solution required to back-titrate the excess acid = V ml Volume of 0.1 N H2SO4 used up for reaction with the ammonia evolved = (50 V) ml (50 V) ml 0.1 N H2SO4 = (50 V) ml of 0.1 N NH3 1000 ml of 1 N NH3 = 17 g of ammonia = 14 g of nitrogen 1000 ml of 0.1 N NH 3 corresponds to 1.4 g of nitrogen. (50 V) ml of 0.1 N NH3 corresponds to Percentage of nitrogen =
(50 − V) × 1.4 g of nitrogen. 1000
(50 − V ) × 1.4 100 × W 1000
Notes I: This is the minimum time required for decomposition and digestion. The duration may be more for certain compounds, for example, nitrogen containing polymeric compounds may require 1012 hrs. II: In case such an apparatus is not available, then simple steam distillation may be used. A water condenser would be inserted between the incoming ammonia and the flask containing standard sulfuric acid.
7.9 ESTIMATION OF AMINO (–NH2) GROUP The estimation of an amino group can be accomplished in the same manner as of an alcoholic group, i.e., by acetylation in the presence of acetic anhydride and dry pyridine, as in the case of alcohols and phenols.
Chemicals Acetic anhydride distilled. Sodium hydroxide solution (0.5 N, 20 g/l). Dry pyridine.
157
ESTIMATION OF FUNCTIONAL GROUPS
Procedure: Prepare the acetylating mixture described as before (Section 7.1.1). In a 250 ml Erlenmeyer flask fitted with a water condenser, weigh accurately about 11.5 g of the amine (aniline, benzylamine, a-naphthylamine, etc.) sample and add 9 ml of the acetylating mixture. Reflux the contents for 45 minutes with frequent stirring. After this period, cool the flask under tap water. Add 15 ml of water to the flask slowly and swirl the flask, cool in ice water. Titrate against 0.5 N sodium hydroxide solution immediately. Also carry out a blank simultaneously using 9 ml of the reagent only.
Calculations Calculate the number of amino groups as was done in the case of alcoholic OH group estimation.
7.10 ESTIMATION OF THE NUMBER OF AMIDE
The number of
GROUPS
groups in an amide may be estimated by its hydrolysis with a
known amount of alkali and back-titrating the unused alkali with a standard acid.
Chemicals Sodium hydroxide solution ( 2 N, 80 g/l). Hydrochloric acid ( 1 N). Procedure: Weigh accurately 0.51 g sample of the amide (benzamide, acetamide, etc.) in a 250 ml round-bottomed flask and dissolve in a small amount of aqueous ethanol. Add 2025 ml of 2 N sodium hydroxide solution and shake. Fit the flask with a water condenser and heat on a sand-bath till the hydrolysis is complete (Note I). This may take 23 hrs. Cool and titrate excess alkali against standard acid using phenolphthalein indicator. Note the volume of the acid consumed.
Calculations Weight of the amid sample taken = W g Vol. of 1 N HCI used
= V ml
1000 ml of 1 N NaOH
= 1 g mol. wt. of NaOH = 1 g mol. wt. of HCI = 1 amide group
158
LABORATORY MANUAL OF ORGANIC CHEMISTRY
V ml of 1 N NaOH will correspond to V/1000 amide groups W g of the amid contains V/1000 amide groups M g (molecular weight) of the amide contains V/1000 × M/W amide groups Note I: Hydrolysis may be completed when no more ammonia gas is evolved.
Question 7.7 Write a chemical reaction for the hydrolysis of an amide in the presence of aqueous acid.
7.11 ESTIMATION OF GLYCINE (Amino Acid) Glycine cannot be estimated directly by titrating with a standard alkali because of the opposing effects of the basic and the acid groups it being a bi-functional compound. The acid is, therefore, first treated with formaldehyde (it is used in the form of an aqueous solution called formalin ) followed by titration with an alkali. But since glycine exists as a zwitterion, it does not react with formaldehyde directly. The acid is therefore converted into its sodium salt by treatment with sodium hydroxide solution which then undergoes reaction with formaldehyde. The following chemical reactions are involved.
It will be noted that the carboxyl group is not involved.
Chemicals Formaldehyde solution (formalin (40%). Sodium hydroxide solution (0.1 N, 4 g/l). Procedure: Weigh accurately 22.5 g of glycine sample in a 250 ml measuring flask, dissolve it in distilled water and fill to the etched mark. Take about 50 ml of 40% formalin from the burette in an Erlenmeyer flask and add 24 drops of phenolphthalein indicator. From a second burette add 0.1 N sodium hydroxide solution, shaking till the solution is faintly pink
159
ESTIMATION OF FUNCTIONAL GROUPS
(Note I ). Pipette 25 ml of glycine solution prepared above in a second Erlenmeyer flask and add 2 drops of phenolphthalein and make it faintly alkaline by the addition of sodium
hydroxide solution ( Note I). To this add 10 ml of the above neutralized formalin solution. The pink color disappears and the solution becomes sufficiently acidic. Titrate the mixture against 0.1 N sodium hydroxide solution till the pink color is restored and note the volume of alkali consumed.
Calculations Weight of glycine taken = W g
Assume 25 ml of the standard glycine solution ( after adding formaldehyde) require V ml of 0.1 N NaOH 250 ml will require 250/25 × V ml of 0.1 N NaOH or V ml of 1 N NaOH 1000 ml of 1 N NaOH = 75 g of glycine 1 ml of N NaOH = % purity of glycine =
V × 75 g of glycine 1000 V × 75 100 × W 1000
The calculation in based on the fact that 1000 ml of 1 N NaOH corresponds to 1 mole of glycine or 75 g of glycine. Thus knowing the molecular weight of the acid its purity can be determined, also if the basicity is given then the molecular weight of the amino acid can also be obtained. Note I: These operations are carried out before mixing the two solutions because formalin contains invariably some formic acid while the amino acids are seldom completely neutral.
Question 7.8 What is the function of adding formalin?
7.12 DETERMINATION OF PERCENTAGE PURITY OF GLUCOSE (A REDUCING SUGAR) Glucose, a reducing sugar, may be estimated by titrating with a standard Fehlings solution, This solution should be prepared fresh when needed since it deteriorates on keeping. Unless a great care is exercised this estimation may not yield good results.
160
LABORATORY MANUAL OF ORGANIC CHEMISTRY
Chemicals Fehlings solution A. Fehlings solution B. Glucose ( AR grade).
Preparation of Fehlings Solution
Solution A: Dissolve accurately weighed 17.32 g of crystalline cupric sulfate ( Copper sulfate. 5H2O) in distilled water and make the solution to 250 ml in a volumetric flask. Solution B: Dissolve 86.5 g of sodium potassium tartarate (Rochelle salt) in warm water in a breaker. Also dissolve 3.5 g of pure sodium hydroxide in water in another beaker. Mix the two solutions and cool. Transfer the solution in a 250 ml volumetric flask and fill it to the mark.
Procedure: The Fehlings solution (combined A and B) can be standardized by titrating with a standard solution of glucose. For this weigh accurately 1.25 g of glucose in a 250 ml measuring flask, dissolve in water and make up the solution to the mark. In an Erlenmeyer flask pipette equal amounts, i.e., 10 ml of each solutions A and B. Titrate this solution (total 20 ml) with glucose solution taken in a burette. Add 1 ml solution of glucose at a time in the beginning and boil the contents after each addition. Near the end-point add 12 drops at one time. The reaction is complete when the blue color has completely disappeared (Note I). Note the volume of glucose solution. From this calculate the weight of glucose equivalent to 1 ml of the Fehlings solution. Normally it is found that 1 ml of the Fehlings solution is equal to 0.0051 g of glucose and 0.0053 g of fructose. Similarly take another 20 ml of the combined Fehlings solution and titrate with the unknown glucose sample solution (assume 100 ml sample is provided).
Calculations Assume 20 ml of the Fehlings solution requires V ml of the unknown glucose solution. Since 1 ml of the Fehlings solution = 0.0051g of glucose Therefore, 20 ml
= 20 × 0.0051 g of glucose
V ml of unknown glucose solution = 20 × 0.0051 g of glucose 100
Therefore
=
20 × 0.0051 × 100 g of glucose V
20 × 0.0051 × 100 g of glucose has been dissolved in 100 ml unknown solution. V
If the weight ( W) of the impure glucose sample is known, then the percentage purity can be calculated.
161
ESTIMATION OF FUNCTIONAL GROUPS
Percentage purity =
20 × 0.0051 × 100 × 100 / W V
Note I: To check for the completion of the reaction, place a drop of the solution with the help of
[
]
glass rod on a glazed tile. Add a drop of K 4 Fe(CN )6 solution (5% solution in 10% glacial acetic acid). Absence of any red precipitate of cupric oxide indicates that the end-point has reached.
7.13 ESTIMATION OF SAPONIFICATION VALUE OF AN OIL OR FAT Natural oils or fats are esters primarily of glycerol and certain long chain carboxylic acids possessing an even number of carbon atoms per molecule. Those which are liquids at ordinary temperature are called oils. Saponification value of an oil or fat may be described as the number of milligrams of potassium hydroxide required to hydrolyse one gram of an oil or fat. It is an indication of the average molecular weight of the fat or the length of the carbon chain of the fatty acid. It is determined on a known weight of an ester which is hydrolysed with an excess of alkali, the unused alkali is back titrated with a standard acid.
Chemicals Alcoholic potassium hydroxide solution ( 0.5 N). Hydrochloric acid (0.5 N and 0.1 N). Preparation of alcoholic potassium hydroxide solution Weigh 5 g of pure potassium hydroxide pellets and dissolve in 250 ml of 95% ethanol in a stoppered bottle. Keep the solution overnight. Filter and standardize against 0.1 N hydrochloric acid solution using phenolphthalein as indicator. Procedure: Weigh accurately 0.51 g of an oil or fat in a 100 ml round bottomed flask. Add 50 ml of standard 0.5 N alc. potassium hydroxide solution. Reflux on a steam-bath till the solution is clear (it may take 1.52 hrs). Cool and dilute it to 250 ml in a volumetric flask.
162
LABORATORY MANUAL OF ORGANIC CHEMISTRY
Pipette out 25 ml of this solution and titrate against 0.1 N hydrochloric acid using phenolphthalein as indicator.
Calculations Weight of the oil or fat taken = W g Assume 25 ml solution requires V ml of 0.1 N HCl and 250 ml solution would require = 250/25 × V ml of 0.1 N HCl = 10 × of V ml 0.1 N HCl =
10 × V × 0.1 ml of 0.1 N HCl 0 .5
= 2V ml of 0.1 N HCl Volume of 0.5 N KOH used = (50 2 V) ml 1000 ml of 1 N KOH = 56 g of KOH 1000 ml of 0.5 N KOH = 28 g of KOH (50 2 V) ml of 0.5 N KOH =
(50 − 2 V) × 28 g of KOH 1000
W g of the fat requires =
(50 − 2 V) × 28 g of KOH 1000
1 g of the fat requires =
(50 − 2 V) 28 × g of KOH 1000 W
(50 − 2 V) 28 × × 1000 mg of KOH 1000 W
or
Therefore, by definition this is the saponification value of the oil or the fat.
7.14 DETERMINATION OF IODINE NUMBER OF AN UNSATURATED COMPOUND The number of
double bonds or olefinic unsaturation in a compound can be
determined by catalytic hydrogenation, i.e., H2 with Pt or Raney nickel as catalyst. The volume of hydrogen gas absorbed is measured and the number of double bonds can be
163
ESTIMATION OF FUNCTIONAL GROUPS
estimated. Most of the classical methods for the determination of unsaturation were concerned primarily for the analysis of animal and vegetable fats and oils. The unsaturation value so determined were expressed as iodine number or bromine number. This value represents the amount of free halogen in grams required for 100 g of the sample molecule. These value display considerable variation by the use of different halogens and thus are of little quantitative organic analysis. Nevertheless, the determination of iodine number will be described here.
Chemicals Wijs solution. Potassium iodide solution (15%). Sodium thiosulfate solution (0.1 N, 24. 8 g/l). Starch indicator. Preparation of Wijs solution: This is simply iodine monochloride solution in acetic acid. It is prepared by dissolving 7.9 g of pure iodine trichloride in 100 ml of glacial acetic acid in a beaker by warming on a water-bath. In another flask dissolve 8.7 g of resublimed iodine in a second portion of warm glacial acetic acid. Mix the two solutions in a 1000 ml volumetric flask and make up the solution to the mark with glacial acetic acid. Store the Wijs solution in a well stoppered amber bottle. Procedure: Weigh accurately 0.150.3 g oil or fat ( cotton seed oil, corn oil, peanut oil, etc. ) in a 250 ml glass-stopped flask (Iodine flask) . To this add 2530 ml of chloroform or carbon tetrachloride to dissolve the sample, warm if necessary. To the solution add 25 ml of the Wijs solution, stopper the flask and shake vigorously for a few minutes. Allow the flask to stand for 30 min with occasional shaking. After this period, add 25 ml of potassium iodide solution and dilute the mixture with 50100 ml of water. Titrate it immediately against 0.1 N sodium thiosulfate solution taken in a burette. Shake vigorously after each addition and again titrate until the yellow color almost disappears. Add starch solution and titrate again to the disappearance of the blue color. Simultaneously perform a blank titration using 25 ml of the iodine monochloride solution.
Calculations The iodine number can be calculated from the following formula: Iodine number =
(V1 − V2 )× N × 127 × 100 W × 1000
Where W represents the weight of the sample. V1 volume of Na2S2O3 solution used for the sample. V2 volume of Na2S2O3 solution used for blank. N normality of Na2S2O3 solution.
164
LABORATORY MANUAL OF ORGANIC CHEMISTRY
7.15 ESTIMATION OF THE REACTION CONSTANT (H) Considerable work has been done to describe the effect of substituents on molecular reactivity in a qualitative fashion. Hammett, however, proposed a quantitative relationship between structure and reactivity. Benzoic acid ionizes according to the following equation:
where K represents the ionization constant. The negative logarithm of K denoted by K a may be taken as a measure of the acid strength. Presence of polar substituents on the benzene ring will increase or decrease the acid strength. This influence of substituents can be realized from the well known Hammett equation, formalized in the following manner: log K/Ka = r s where K and K a are the ionization constants of substituted and unsubstituted benzoic acids s is the substituent constant. r is the reaction constant. A plot of log K/Ka against s is linear with slope equal to r. The reaction constant measures the susceptibility of a reaction to the polar effects of the substituents. The magnitude of the value of r indicates that the reaction in sensitive to the polar effects. It provides information about the nature of the transition state involved in the reaction. A negative value of r shows that the reaction in aided by electron-donating groups and vice versa. To estimate r several substituted benzoic acids are taken and pKas are determined. Since Ka =
and at half-equivalence
[ArCOO ] = [ArCOOH]
K a = H+ +
or
pKa = log H = pH Therefore, a plot of the Hammet equation is drawn between pK (substituted), pKa
(unsubstituted) versus s. The s values for several substitutents have been determined and are given in Table 7.1.
165
ESTIMATION OF FUNCTIONAL GROUPS
Table 7.1: Substituent Constant (σ) Values Group
σm
σp
NH 2
– 0.161
– 0.660
CH2
– 0.069
– 0.170
OH
– 0.002
– 0.357
H
–0
–0
NO 2
0.710
0.778
Cl
0.373
0.227
CN
0.678
0.628
Br
0.390
0.232
Chemicals • Benzoic and substituted benzoic acids. • Sodium hydroxide solution (0.01 N, 0.4 g/l). Procedure: Weigh accurately about 0.2 g benzoic (Note I) in a 100 ml Erlenmeyer flask. Dissolve it in one-half equiv. of standard 0.01 N sodium hydroxide solution in 50 ml of ethanol (Note II). Let the solution equilibrate (it may take 30–45 min), then note the temperature. Measure the pH of this solution on a pH meter and calculate the corresponding pKa. Draw a plot between pKa and σ of the corresponding acids and obtain ρ. Notes I: Each student is assigned an acid. II: For 0.2 g (0.001 mole) of benzoic acid, 0.0005 equiv. of sodium hydroxide (half equiv.) is needed. If sodium hydroxide is 0.01 N, then use 5 ml of this solution.
7.16 DETERMINATION OF CHEMICAL OXYGEN DEMAND (COD) Presence of carbonaceous organic matter tends to deplete the concentration of oxygen in waste waters which is so important for the life of aquatic animals. The COD determination is a measure of the oxygen equivalent of that portion of organic material that is oxidized by a strong oxidizing agent. The value is reported as mg/l of COD. It is an easily determined parameter and is important in the control of waste in treatment plants.
Chemicals • Potassium dichromate solution (0.25 N, 10.26 g/l). • Ferrous ammonium sulfate solution (0.1 N, 39.2 g/l).
166
LABORATORY MANUAL OF ORGANIC CHEMISTRY
Mercuric sulfate crystals. Sulfuric acid and silver sulfate (dissolve 0.45 g of silver sulfate in 5 kg conc. sulfuric acid and leave for two days). Ferroin indicator. Procedure: In a 250 ml round-bottomed flask equipped with a reflux condenser place 0.4 g
of mercuric sulfate (Note I), 20 ml of waste water sample (Note II) and mix. Add to this mixture 10 ml standard potassium dichromate solution followed by 30 ml sulfuric acid
containing silver sulfate ( Note III) , with constant shaking. Add boiling chips, replace, the condenser and reflux for 2 hrs to oxidize the carbonaceous matter. Cool and wash the condenser with 20 ml of distilled water. Transfer the mixture to a 250 ml Erlenmeyer flask. Rinse the round-bottomed flask twice with distilled water. Titrate against 0.1 N ferrous ammonium sulfate solution using 23 drops of ferroin indicator. The end-point is indicated by a change of color from blue-green to reddish brown. A blank using 20 ml of distilled water should also be run simultaneously.
Calculations mg/l COD = where
(V − V1 ) N × 8000 ml sample
V ml of ferrous ammonium sulfate solution used for blank. V1 ml of ferrous ammonium sulfate solution used for the sample. N normality of ferrous ammonium sulfate solution.
Compare the result with other classmates. Notes I: It is used to scavenge the chloride ions. II: A sewage sample may be obtained. III: It is used as a catalyst.
7.17 ESTIMATION OF KETO-ENOL EQUILIBRIUM OF A KETO ESTER Equilibrium constant of ethyl acetoacetate Ethyl acetoacetate, either in solution or in pure state, consists of an equilibrium mixture of two forms known as tautomers. The two forms differ in the position of a hydrogen atom. This phenomenon is known as keto-enol tautomerism. The equilibrium is determined by an indirect method by treating ethyl acetoacetate with bromine ( in the presence of bnaphthol) since the enolic form reacts at a much faster rate than the keto form. The solution cannot be titrated directly with bromine as HBr generated catalyzes keto-enol tautomerization.
ESTIMATION OF FUNCTIONAL GROUPS
167
The function of b-naphthol is to remove excess bromine.
Chemicals Bromine 0.1 M in CH3OH (16 g/l). Potassium iodine solution 0.1 M in H 2O ( 15.6 g/l). Sodium thiosulfate solution 0.1 M (24.8 g/l). b-Naphthol solution 10% in CH3OH. Procedure: Weigh accurately 6.5 g of ethyl acetoacetate in a 100 ml volumetric flask and fill it to the mark with methanol to give 0.5 M solution. (Note I) Pipette 10 ml of this solution in a 250 ml Erlenmeyer flask. Add 10 ml of 0.1 M bromine solution and shake. Immediately add 10 ml of 10% solution of b-naphthol (Note II ). Shake the flask vigorously for 2 min. Add 25 ml of app. 0.1 M aqueous potassium iodide solution and allow to stand for 15 min at room temperature with occasional shaking. Then titrate against standard sodium thiosulfate solution (no indicator ). The solution passes from a wine-red to a colorless form to a light yellow color (Note III). Note the volume of sodium thiosulfate solution consumed.
168
LABORATORY MANUAL OF ORGANIC CHEMISTRY
Calculations Assume volume of 0.1 M Na 2S2O3 solution used = V ml V ml of 0.1 M Na2S2O3 = V/2 ml of 0.1 M I2 = V/20 milli equivalents of 1 N I2 = V/20 milli equivalents of bromo ester = V/20 milli equivalents of enol form = V/20 × 130 mg of enol form = 6.5 V mg of enol form Acetoacetic ester taken = 10 ml of 0.5 M = 10 × 0.5 milli equivalents = 10 × 0.5 × 130 mg = 650 mg Therefore, keto from = 650 6.5 V Keq =
6.5V 650 − 6.5V
This value is around 0.07. Notes I: The concentration of the ester should be known exactly. II: Use a graduated cylinder to measure bromine and b-naphthol solutions. III: The end-point should persist for at least 3 min.
Questions 7.9 Why does the enolic from react with bromine? 7.10 Why is it not necessary to know the exact concentration of Br 2 and b-napthol?
7.18 DETERMINATION OF THE NUMBER OF METHOXY (–OCH3) GROUPS The methoxy group is estimated according to the procedure of Zeisel. A known weight of the compound is decomposed by refluxing with hydroiodic acid whereby it is converted into volatile methyl iodide. It is washed free of hydrogen iodide and iodine and then absorbed in a 4% alcoholic silver nitrate solution. Silver iodide is weighed and estimated gravimetrically as AgI. R OCH 3 + HI
R OH + CH3I
169
ESTIMATION OF FUNCTIONAL GROUPS
A rather more convenient procedure is to absorb the liberated methyl iodide in acetic acid and sodium acetate solution containing bromine and then estimated volumetrically. First iodine monobromide is formed which is further oxidized to iodic acid. Then potassium iodide solution is added to liberate iodine which is titrated against standard sodium thiosulfate solution. The following reactions take place: CH3I + Br2 IBr + 2 Br2 + 3 H2O HIO3 + 5 HI 3 I2 + 6 Na 2S2O3
CH3Br + IBr HIO 3 + 5 HBr 3 I 2 + 3 H 2O Nal + Na2S4O6
Apparatus The apparatus employed is shown in Fig. 7.3. It consists of a pyrex glass two necked roundbottomed flask A. A Liebigs condenser C and a trap D is fitted in one joint and an inlet carbon dioxide tube B is attached to the second joint. The trap D is connected to two receivers E and F. The reaction flask A is immersed in an oil-bath. The left hand side assembly H is a device by means of which the vapor of chloroform boiling in the flask can be passed through the condenser C.
Chemicals Acetic acid-sodium acetate-bromine solution. Dissolve 10 g anhydrous sodium acetate in 100 ml glacial acetic acid. Add 0.3 ml of bromine per 10 ml of solution before use. Sodium acetate solution ( 25%). Sulfuric acid (10%, V/V). Sodium thiosulfate solution (0.05 N, 12.25 g/l) . Starch indicator. Procedure: Pour antimony sodium tartarate ( 810% solution in water) solution in trap D enough to conver the internal tube. This solution will retain hydroiodic acid and Iodine. Charge the tubes E and F with equal quantities (1012 ml) of acetic acid-sodium acetatebromine solution. Weigh 2025 mg of the sample accurately in a tin foil cup, fold it and drop it into the flask A through the inlet B. Also add 0.5 g of phenol, 1.0 ml of distilled propionic anhydride and a few chips of carborundum (Note I). Dissolve the sample completely by warming and introduce 10 ml of hydroiodic acid (Note II) through B and immediately replace the tube and connect to the carbon dioxide source a Kipps apparatus. Now pass chloroform vapors through the condenser C for 10 min and start heating the oil-bath. Adjust the passage of the carbon dioxide through the inlet tube so that the rate of bubbling in the receivers E and F is 12 bubbles/min. If the rate is too rapid some hydroiodic acid will escape absorption.
170
LABORATORY MANUAL OF ORGANIC CHEMISTRY
The oil-bath should attain temperature of 140°C in about 75 min. During this period the reaction is usually complete. In a 250 ml flask fitted with a glass stopper and containing 10 ml of 25% sodium acetate solution, transfer the contents of receivers E and F. The sodium acetate is required to buffer the HBr formed. To destroy excess of bromine, formic acid (90%) is added dropwise unit the smell of bromine is no longer detected (Note III). Replace the stopper and shake the flask. Dilute the contents of the flask to 100 ml with water , 1 g of potassium iodide and 10 ml of sulfuric acid, stopper the flask immediately, swirl gently, allow to stand undisturbed for 3-4 min. The solution is then titrated against standard thiosulfate solution, using starch indicator. A blank may be run using phenol and propionic anhydride.
Fig. 7.3 Assembly for the estimation of methoxy group.
Calculations According to the equations above a convenient conversion factor is obtained as follows:
–OCH3
CH3 I
HIO3
3 I2
6 Na2S2 O3
Weight of the compound taken = W g Volume of 0.05 Na2S2O3 required = V1 ml 6 × 1000 ml, 1 N Na2S2O3 solution = 31 g OCH3 groups 6 × 20 × 1000 ml, 1 N Na2S2O3 solution = 31 g OCH3 groups V1 ml of 0.05 N of Na2S2O3 solution =
31 × V1 g OCH3 groups 120,000
171
ESTIMATION OF FUNCTIONAL GROUPS
Therefore, W g of the unknown contains
Percentage OCH3 group =
31 × V1 g OCH 3 groups 120,000
31 × V1 × 100 =X 120,000 × W
If the molecular weight (M) of the unknown is given then the number of methoxy groups is given by: M× X OCH 3 groups (One OCH 3 group = 31). 100 × 31 Notes I: These reagents help dissolve as alkoxy compound. Chips of carborundum prevent bumping. II: The constant boiling acid ( b.p. 120°C/760 mm ) containing 57% of hydroiodic acid is satisfactory. III: To test destruction of bromine add a drop of methyl red indictor. Decolorization indicates the presence of bromine. Add more formic acid.
7.19 DETERMINATION OF ASCORBIC ACID CONCENTRATION Vit. C is also known as ascorbic acid. It is found in a wide variety of fruits and vegetables. Good sources include: broccoli, lemon, oranges, kiwi fruit, tomatoes, papaya, leafy greens, brussels sprouts, etc. Vit. C is an antioxidant and helps prevent ageing of skin. Concentration of ascorbic acid ( Vit. C ) in fruit juice (lemon, orange) or Vit. C tablets
(Celin ) can be determined by titrating against a solution of 2, 6-dichlorophenol indophenol dye. This dye gives pink coloration in acid solution.
172
LABORATORY MANUAL OF ORGANIC CHEMISTRY
Chemicals Dye Solution: Dissolve sodium salt of the dye (0.125 g) in 240 ml of distilled water in a 250 ml volumetric flask. Make up to the mark with phosphate buffer (equivalent to 0.0165 of K2HPO 4 and 0.0202 g of KH2PO 4 per 250 ml of the solution ).
Standard Ascorbic Acid Solution: Dissolve (just before use) pure 10 mg ascorbic acid in distilled water in a 100 ml volumetric flask.
Source of Vitamin C A vitamin C tablet or fruit juice can be used to estimate the amount of Vit. C.
Vitamin C Tablet Take a Vit. C tablet containing minimum 100 mg of the vitamin. Weigh the tablet accurately. Crush it on a filter paper and transfer the powder to a 100 ml Erlenmeyer flask. Add 500 ml of a cold 1% oxalic acid solution in distilled water. Leave it for some time. Filter the mixture directly into a 1000 ml volumetric flask. Wash the Erlenmeyer flask and the filter paper with 200 ml, 1% oxalic acid solution into the volumetric flask. Fill the flask to the mark with additional 1% oxalic acid solution and mix thoroughly. For calculating the normality of the dye against a standard ascobic acid sample. The normality and the amount of Vit. C can be determined using 5 ml of Vit. C solution.
Fruit Juice Filter 10 ml of orange juice either from the fruit (orange) or from canned juice to remove the pulp. With the help of a burette, transfer 5 ml of the juice in a 50 ml volumetric flask. Dilute the orange juice with 1% oxalic acid solution up to the mark. Procedure: In a clean 100 ml Erlenmeyer flask, pipette 5 ml of juice (Vit. C tablet or fruit juice). Titrate it with 2, 6-dichlorophenolindophenol dye taken in a burette with constant shaking. The end-point is reached when a pink color is obtained. Also carry out a blank without the sample using 5 ml of distilled water only. This is an alternative method to the one described under Vit. C.
Calculations Weight of ascorbic acid dissolved in 100 ml = W g distilled water Volume of dye needed for fruit juice
= V ml
Volume of dye needed for ascorbic acid
= V1 ml
Volume of dye needed for blank
= V2 ml
173
ESTIMATION OF FUNCTIONAL GROUPS
Total amount of Vit. C in fruit juice =
V − V2 × W × Dilution factor V − V1
Dilution factor: In the above case 5 ml fruit juice is diluted to 50 ml therefore, the dilution factor is equal to 10.
7.20 DETERMINATION OF MOLECULAR WEIGHT OF A SUBSTANCE (RAST’S METHOD) The melting (or freezing) point of a pure substance is depressed when an impurity is added. This lowering can be expressed in quantitative form as: Tf = K f m
where Tf is the lowering in freezing point of solute. Kf is the molal depression constant. In Rasts method camphor is used as a solvent because in the molten state it has a high solvent power for organic compounds. Moreover, because of its large molecular depression constant it permits the observation of depression with an ordinary thermometer.
Chemicals Naphthalene, camphor, acetanilide. Determination of molecular weight of acetanilide involves the following two steps: Determination of Kf for camphor: Weigh a clean, dry weighing bottle and place about 0.2 g of naphthalene in it and determine its accurate weight. Add approximately 2 g powdered camphor and also determine the accurate weight of the mixture. Put a glass stopper on the weighing bottle and gently heat on a flame to obtain a clear solution. Shake the bottle to get a homogeneous solution. Cool and withdraw a small portion of the solidified mixture and determine the melting point of the mixture in a capillary tube. Repeat to obtain a satisfactory melting point. Determination of molecular weight of acetanilide: Repeat the procedure described in the above step using approximately the same amounts of chemicals but replace acetanilide for naphthalene. Determine a satisfactory melting point of the mixture.
Calculations Weight of naphthalene = W g Weight of camphor = W1 g Freezing point of the mixture = t°C (mean of 23 determinations) Depression of freezing point = (176 t)°C
174
LABORATORY MANUAL OF ORGANIC CHEMISTRY
where 176°C is the melting point of camphor. W1 g of naphthalene dissolved in W g of
camphor causes a depression of (176 t)°C.
128 g (mol. weight of naphthalene) of naphthalene in 100 g of camphor will cause a depression of: Kf =
(176 − J ) × 1289 91 × 1000
This is the value of Kf Weight of acetanilide = w g Weight of camphor = W g Freezing point of the mixture = t°C Depression of freezing point = (176 t 1)°C w g of acetanilide dissolved in W1 g of camphor causes a depression of (176 t 1)°C. Molecular weight =
w × K f × 1000 W × (176 − t1 )
.
Chapter
8
ORGANIC PREPARATIONS
The student of organic chemistry is also concerned with an important class of laboratory experiments, i.e., organic preparations. It is necessary, therefore, to give an adequate training in this area, such exercises will give the necessary experience and confidence to work later as a skilled research work. The synthetic experience gained at the laboratory stage can be adopted on a large scale. It is intended to describe a number of diverse experiments which meet a number of criteria, i.e., be readily performable within the stipulated laboratory period, cover adequately some concept of organic chemistry and finally the experiment poses some interesting questions in the mind of the student. Furthermore, the selection of experiments is also governed by the ease of the availability of chemicals and essential apparatus. Laboratory procedure and synthetic experiments of various compounds of proven value will be discussed. As far as possible, experiments that involve a certain analytical technique; concept or reaction type have been grouped together. All the experiments will utilise the techniques discussed in Chapter 2. It is important to note that all organic compounds are potentially dangerous and fire hazards are large, and many compounds are poisonous. One should, therefore, be aware of the potential dangers and for safe working, the fume hood should be used as much as possible.
8.1 ELECTROPHILIC AROMATIC SUBSTITUTION REACTIONS In an electrophilic reaction, a hydrogen on the benzene ring is replaced by a strong electrophilic i.e., a positively charged species. Several types of reagents yield substitution products. This reaction is irreversible.
where
176
LABORATORY MANUAL OF ORGANIC CHEMISTRY
An electron deficient species is always the attacking reagent. Electrophilic aramatic substitution reactions are the most widely studied reactions in organic chemistry.
8.1.1 Preparation of Nitrobenzene (Nitration) Aromatic compounds can be nitrated by a variety of nitrating agents. Though a mixture of concentrated nitric acid and concentrated sulfuric acid is frequently employed.
(
)
Mechanistically a nitronium ion NO2+ is first produced form nitric acid and sulfuric acid which attacks the aromatic ring as outlined in the following steps:
Procedure: Take a 200 ml round-bottomed flask fitted with a cork holding a thermometer
(the
bulb extends to the bottom of the flask) and a glass tube (air-condenser) about 30
inches long. Place 16 ml of conc. nitric acid (d 1.42) and 17 ml of conc. sulfuric acid (d 1.84) and cool the nitrating mixture in cold water. To this mixture add dropwise with constant shaking 15 ml (13 g) of benzene. During the addition the temperature should not rise above
60oC (Note I ). Cool the flask in a bath of ice-cold water if necessary. After the addition is complete replace the condenser and warm the flask on a water-bath for 50 min maintaining a temperature between 5060oC. Shake the flask occasionally. Cool and pour the contents in a beaker containing 100 ml of water. Transfer the mixture to a small separatory funnel,
177
ORGANIC PREPARATIONS
and shake. Save the lower organic layer and discard the upper aqueous phase. Wash the organic layer twice with 60 ml portions of water followed by 15 ml of 1 M sodium hydroxide solution and again with water to remove excess nitric acid. Take the organic layer in an Erlenmeyer flask and shake with anhydrous calcium chloride to dry nitrobenzene and filter in a 50 ml distillation flask. Distil using an air-condenser and collect the fraction boiling between 206210oC (Note II). Nitrobenzene is obtained as a clear pale yellow liquid yield, 15-16 g. Notes I: If the temperature is allowed to rise above this limit then dinitration of benzene takes place. II: Do not distil to dryness as the brown mass consisting of m-dinitrobenzene and higher nitro compounds may decompose and cause explosion.
Questions 8.1 Why should the temperature not rise above 60 oC? 8.2 What will happen if the temperature is lowered to 10 oC? 8.3 How will the absence of sulfuric acid influence the rate of nitration?
Calculation of percentage yield of a product One way to determine the success of a synthetic process is to check the yield of the product and purity. The yield is generally expressed as the percentage yield.
Percentage yield =
Actual yield of the pure product × 100 Theoretical yield
Usually, all but one of the reactants are present in excess of the stoichiometric amounts in a preparation. The percentage yield is calculated here by considering the above nitration experiment. In this case nitric acid and sulfuric acid are present in excess, therefore, calculation is made on the basis of benzene alone. From the equation it is evident that theoretically 78 g benzene would yield 123 g of nitrobenzene. Using 13 g of benzene, the theoretical yield would be
13 × 125 = 20.5 g. . 78
The actual yield obtained is 16 g. Thus the percentage yield is equal to
16 × 100 = 77.3 20.5
178
LABORATORY MANUAL OF ORGANIC CHEMISTRY
Yields are obtained frequently in the range of 5580% and are considered satisfactory. In a preparation a yield of 100% in impossible to obtain because loses occur during work-up. However, yields of > 99% are reported as quantitative.
8.1.2 Preparation of o- and p-Nitrophenols Some substances, such as phenol, may be nitrated readily even with dilute nitric acid in aqueous solution. In other cases, acetic acid, acetic anhydride or some other solvent is employed.
The nitration is facilitated under mild conditions because phenol contains a strong activating hydroxyl group and dilute nitric acid is sufficient to introduce the nitro group. The temperature should be controlled otherwise tarry oxidation products are formed. Procedure: In a 250 ml bolt-head flask, mix 18 ml of conc. sulfuric acid with 55 ml of water
(Note I). Dissolve 20 g sodium nitrate in this solution and cool in a cold water-bath. In a
dropping funnel mix 12.5 g of melted phenol with 2.5 ml water to form an emulsion. Add this emulsion to the above solution with constant stirring at such a rate that the temperature does not rise above 20 oC. After the addition is complete, leave the mixture at room temperature for 1 hr shaking occasionally. Then add 50 ml of water, shake well and allow to stand. Decant the aqueous layer and discard it. Repeat this process of washing 23 times with water to ensure the removal of the acid. At this stage a crude mixture of o- and pnitrophenols is obtained.
Separation of the isomers The two isomers are separated by steam distillation. The ortho-isomer is more volatile and less soluble due to H-bonding, while the para-isomer is less volatile and more soluble. To the above residue add 50 ml of water and steam distil the mixture whereby o-nitrophenol passes over. The distillation is considered complete when the solidification of phenol is no longer observed in the condenser. Cool the distillate, o-nitrophenol solidifies in the receiving flask. Filter the solid at the pump on a Buchner funnel and dry in a desiccator. The yield of o-nitrophenol is 3.9 g, m.p. 46 oC. Cool the residue in the distillation flask in an ice-bath for 20 min, and p-nitrophenol solidifies. Filter the solid on a Buchner funnel and wash with water. Transfer the solid to a beaker and boil with 150 ml of 2% hydrochloric acid and 0.4 g of activated charcoal. Filter
ORGANIC PREPARATIONS
179
the hot solution and allow the filtrate to crystallize. Colorless crystals of p-nitrophenol are obtained. The yield is 2.6 g, m.p. 112oC. Note I: Acid should be added to water very slowly. Instead 21 ml of conc. nitric acid and 51 ml of water may be used.
Questions 8.4 Why does o-nitrophenol distil over but not the p-isomer? 8.5 Which of the two isomers is more soluble in water and why?
8.1.3 Preparation of 2, 4, 6-Tribromoaniline (Bromination) Similar to the hydroxy group, an amino group is a powerful activating group of benzene ring in an electrophilic substitution reaction. It is frequently difficult to prevent extensive substitution in the activated ring. For instance, when aniline is treated with bromine in glacial acetic acid at room temperature, the only isolated product is 2, 4, 6-tribromoaniline
Procedure: In a 100 ml Erlenmeyer flask dissolve 2.5 g distilled aniline in 10 g glacial
acetic acid. To this add dropwise a solution of 13.5 g (4.2 ml) of bromine dissolved in 10 ml glacial acetic acid (Note I) with constant shaking in a rotatory motion. Since the reaction is exothermic, cool the flask in cold water during addition. After the addition is complete add 50 ml water to the flask. Filter the yellow solid and dry first between the folds of filter papers and then in air. The yield is 4.3 g, m.p. 120oC. Note I: This preparation should be carried out in a good ventilated hood because bromine is an extremely unpleasant chemical.
Question 8.6 Why does polybromination take place in aniline? How can it be controlled?
8.1.4 Preparation of Picric Acid (2, 4, 6-Trinitrophenol) Picric acid is used for the preparation of molecular complexes, i.e., picrates. It can be prepared starting from phenol by consecutive sulfonation and nitration procedures.
180
LABORATORY MANUAL OF ORGANIC CHEMISTRY
Procedure: Place 7.5 g of phenol and 20 ml of conc. sulfuric acid in a dry round-bottomed flask. Shake the mixture and heat on a water-bath for 30 min. During this period a clear solution of o- and p-phenolsulfonic acids are obtained. Cool the flask in an ice-bath. Now add 22 ml of conc. nitric acid dropwise with constant shaking. An exothermic reaction takes place and copious red fumes (oxides of nitrogen) are evolved and the liquid becomes deep
red in color. Heat the flask in a water-bath (80100oC) for 2 hrs with occasional shaking. Cool the mixture and pour it carefully into about 100 ml of cold water. Filter the solid on a Buchner funnel and wash thoroughly with cold water. Recrystallize the crude picric acid from hot aqueous alcohol, yield 11.5 g., m.p. 122°C.
8.1.5 Relative Rates of Electrophilic Aromatic Substitution The subject of electrophilic substitution is discussed in all organic chemistry textbooks. The emphasis is laid more on the orientation corresponding to substituent already occupying a position on the aromatic ring. Only qualitative statements are made about the relative reactivity of various types of compounds. An estimation of the relative rates will be made here by rate comparison also in a qualitative manner. Procedure: The procedure is designed for a class of 10 students. The idea is to study the rate of bromination for a group of aromatic compounds. These compounds may be divided into two groups. First prepare the following solutions: Dissolve 2 g bromine in 250 ml of 90% acetic acid to obtain a 0.05 M bromine solution and use this as stock solution. Dissolve separately 1.56 g benzene in 100 ml ethyl acetate and in separate containers dissolve phenol (2 g), benzoic acid (1.2 g), methyl benzoate
(2.72 g),
chlorobenzene (1.0 g), toluene (1.0 g), p-xylene ( 1.0 g), nitrobenzene ( 1.2 g), each in about 50 ml of ethyl acetate to give a 0.2 M solution. Now place five clean 2 × 15
mm test tubes on a test tube stand. Add 2 ml of each solution (group A ) in each test tube
(Note I) and 2 ml of bromine solution in each tube from a burette. Note the time of addition in each case. Shake the tubes for a few seconds and then put them on the stand (Note II). Record the time for the loss of bromine color in each test tube (Note III) . Discard the solution in the sink ( fume hood), wash with a small quantity of acetone and dry. Repeat the experiment with the second group of compounds ( group B) using the same volumes of reagents followed by bromine solution. Again note the time for the decolorization of bromine color. Record the results in a tabular form.
181
ORGANIC PREPARATIONS
0.2 M compound solution used
0.05 M bromine solution used
C6H6
2 ml
2 ml
C6H5OH
2 ml
2 ml
C6H6OCH3
2 ml
2 ml
C6H5COOCH3
2 ml
2 ml
C6H5COOH
2 ml
2 ml
C6H6
2 ml
2 ml
C6H5Cl
2 ml
2 ml
C6H5CH3
2 ml
2 ml
2 ml
2 ml
2 ml
2 ml
Time for decolorization
GroupA
Group B
C6H5NO2
By a comparison of time it will be noticed that the color disppears faster in case of compounds bearing electron-donating groups. Notes I: Use a pipette fitted with a rubber suction bulb. II: Avoid exposure of tubes to sunlight. III: The reaction is considered to be complete when the solution attains a very pale yellow color. IV: Do not spill bromine. It is a hazardous chemical.
Questions 8.7 Why is chlorobenzene less reactive than benzene in electrophilic substitution? 8.8 List five common electrophilic substitution reactions as applied to aromatic compounds.
8.1.6 The Friedel-Crafts Reaction The Friedel-Crafts reaction is one of the most general aromatic electrophilic substitution reactions for the preparation of alkyl and acyl derivatives of benzene. It is carried out by using a Lewis acid such as anhydrous aluminum chloride as a catalyst. An inert solvent
182
LABORATORY MANUAL OF ORGANIC CHEMISTRY
such as nitrobenzene, carbon disulfide, etc. may be employed if needed. However, if the aromatic compound is an inexpensive liquid hydrocarbon, for example, benzene it is used both as a reactant and a solvent.
8.1.6(a) Preparation of o-Benzoylbenzoic Acid (The Friedel-Crafts Reaction) In the following preparation, benzene and phthalic anhydride in the presence of aluminum chloride are used. The reaction proceeds with the formation of a reactive acylium ion. At least two molar equivalents of anhydrous aluminum chloride be used because the catalyst coordinates both with the reactant and the product.
Procedure: In a 250 ml round-bottomed flask fitted with a water condenser and drying tube to the top of the condenser place 5 g phthalic anhydride and 25 ml thiophene-free
benzene ( Note I) . Then add 10 g anhydrous aluminum chloride ( Note II) and shake vigorously. An exothermic reaction usually commences at this stage with the evolution of hydrochloric acid gas. A gas trap is attached to the top of the drying tube. After the initial reaction has subsided, heat the flask under reflux in a boiling water-bath carefully for 20 min with frequent shaking. Cool the flask in an ice-bath at the end of heating and add 40 g of crushed ice in small lots with constant shaking. Now add 50 ml of water and 7 ml conc.
hydrochloric acid to hydrolyse the addition complex (Note III) . Remove excess benzene by steam distillation. Transfer the remaining solid to a beaker and allow it to cool in ice-bath. Filter the acid on a Buchner funnel at the pump and wash with cold water. Dissolve the solid in 40 ml of 10% aqueous sodium carbonate solution and filter again to remove insoluble aluminum hydroxide. Acidify the filtrate with conc. hydrochloric acid stirring with a glass rod. The acid separates out as a solid. Filter and dry in air.
The acid obtained above usually has a low melting point (approx. 94oC). The pure anhydrous acid can be prepared by dissolving it in 40 ml of benzene in a round-bottomed flask and heating for 15 min. Transfer to a separatory funnel and remove the water layer. Concentrate the benzene solution to half its volume and precipitate the acid by adding petroleum ether, simultaneously cooling it in an ice-bath. Filter the solid and dry in a vacuum desiccator. The yield of the pure acid is 6.51 g, m.p. 128oC. Notes I: Thiophene-free benzene can be prepared by shaking commercial benzene with conc. sulfuric acid several times in a separatory funnel, subsequently washing with water and distilling after drying over anhyd. calcium chloride.
ORGANIC PREPARATIONS
183
II: Weigh anhyd. aluminum chloride in a stoppered bottle as readily as possible. III: Keep the contents of the flask at room temperature.
Question 8.9 What is the principle involved in the preparation of thiophene-free benzene by washing with conc. sulfuric acid?
8.1.6(b) Preparation of Diphenylmethane (The Friedel-Crafts Reaction) In the presence of Lewis acid catalyst such as aluminum chloride, alkyl halides alkylate benzene to give alkylbenzene. The following experiment is an example of benzylation of benzene by the Friedel-Crafts reaction.
The mechanism of the reaction proceeds in the following steps:
Procedure: In a 250 ml round-bottomed flask, place 19.3 g distilled benzyl chloride and 75 ml sodium-dry benzene. Fit the flask with a water condenser, and a gas trap for collecting hydrochloric acid gas evolved in the reaction is connected to the top of the condenser with the help of a rubber tubing. In a stoppered bottle weigh 6 g of anhyd. aluminum chloride
(Note I). Immerse the flask in an ice-bath. Add about 1 g of aluminum chloride through the
condenser and shake. An exothermic reaction commences with the evolution of hydrochloric acid gas. When the reaction has subsided add another 1 g portion of aluminum chloride. Repeat the addition and shake. Keep the flask well cooled. After the addition is complete,
184
LABORATORY MANUAL OF ORGANIC CHEMISTRY
reflux the contents of the flask for 20 min on a boiling water-bath. Allow to cool, add 50 g of crushed ice and 50 ml water to the flask and shake. Transfer the mixture to a separatory funnel. Discard the lower aqueous layer. Wash the benzene layer with 10% hydrochloric acid followed by water. Dry the benzene solution over anhydrous calcium chloride. The dried liquid is filtered into a distilling flask and distilled to remove benzene. Distil the residue using an air condenser and collect diphenylmethane between 250275 oC (b.p. of pure diphenylmethane is 262oC). The yield is 14.0 g. Note I: Usually an excess of anhydrous aluminum chloride in used.
Question 8.10 What are the limitations of the Friedel-Crafts alkylation?
8.1.6(c) Preparation of >-Benzoylpropionic Acid (The Friedel-Crafts Reaction) Succinic anhydride is employed with a large excess of benzene under the Friedel-Crafts conditions.
Procedure: Fit a 250 ml dry round-bottomed flask with a reflux condenser and a drying tube at the top of it. Charge the flask with 4.2 g of succinic anhydride and 25 ml dry benzene. Support the flask over a water-bath in the fume cupboard (Note I) and add accurately
weighed (Note II) 12.5 g powdered anhyd. aluminum chloride in one portion. First cool the mixture. After the exothermic reaction ceases replace the condenser immediately and heat the flask for 30 min. Shake frequently during this period. If an uncontrollable reaction occurs during heating, cool the flask in a bath of cold water again. Pour the cold mixture in a 250 ml beaker and immerse it in ice. To this add slowly with constant stirring 20 ml of 50% hydrochloric acid. Filter the solid on a Buchner funnel at the pump wash the solid with 10 ml cold dil. hydrochloric acid followed by cold water. Dissolve the crude product so
obtained in sodium carbonate solution (5 g of sodium carbonate dissolved in 30 ml of water ) by boiling. Break the lumps with a glass rod. Filter the solution and cool. Acidify the cold filtrate with 13 ml of conc. hydrochloric acid. Filter the solid, wash with cold water and dry. The yield is 7.0 g, m.p. 115o C. Notes I: Because hydrochloric acid gas is evolved. II: Weigh anhyd. aluminum chloride in a dry weighing bottle.
ORGANIC PREPARATIONS
185
8.1.6(d) Preparation of p-Xylene-2-Sulfonic Acid p-Xylene is readily sulfonated to yield sulfonic acid. Since all the four ortho positions are identical only a single sulfonated product is obtained.
Procedure: Place 5 g ( 6 ml) of xylene in a 100 ml round-bottomed flask. With gentle stirring add carefully 10 ml of conc. sulfuric acid. Heat the mixture for 1015 min on a water-bath. Remove the flask and shake till the layer of p-xylene on the surface has disappeared. Cool the flask at room temperature and to it add 50 ml of water and then immerse the flask in ice till a solid appears. Filter the crystalline acid on a Buchner funnel. Recrystallize from a small quantity of boiling water and dry. The yield is 8.2 g, m.p. 82 oC.
8.2 THE DIELS-ALDER REACTION It is an important reaction for the preparation of cyclic compounds. In this reaction a conjugated diene unites with an unsaturated compound (called the dienophile).
The Diels-Alder reaction in an example of cycloaddition reaction, i.e., a reaction which leads to the formation of a ring. The reaction in frequently carried out thermally but in some cases can be achieved in the presence of a Lewis acid.
8.2.1 Preparation of 9, 10-Dihydroanthracene-9 10-=, >-Succinic Anhydride (The Diels-Alder Reaction) Anthracene and maleic anhydride react on heating to form the title compound.
Procedure: Place 3 g of pure anthracene, 30 ml of dry xylene (Note I) and 1.5 g of maleic anhydride in a 100 ml dry round-bottomed flask. Attach a water condenser and reflux the
186
LABORATORY MANUAL OF ORGANIC CHEMISTRY
contents on a water-bath for 25 min with frequent shaking. Cool the mixture and collect the solid on a Buchner funnel. Recrystallize the adduct from ethyl acetate. The yield is 3.3 g, m.p. 262263 oC. Note I : Dry benzene may be used but the refluxing time should be increased. The yield in this solvent may also be low.
Question 8.11 Write the structure of the Diels-Alder product between cyclopentadiene and benzoquinone.
8.3 THE BECKMANN REARRANGEMENT The rearrangement of a ketoxime to an amide under the catalytic action of a strong acid or thionyl chloride is known as the Beckmann rearrangement.
The reaction proceeds according to the following mechanism:
8.3.1 Preparation of Benzanilide This preparation is accomplished in the following two steps: Step A: Preparation of benzophenone oxime The keto oxime is first prepared by a reaction between benzophenone and hydroxylamine hydrochloride.
ORGANIC PREPARATIONS
187
Procedure: Dissolve 3.6 g benzophenone and 4 g of hydroxylamine hydrochloride
(NH2OH.HCI ) in a 100 ml round-bottomed flask in 50 ml ethanol. Add 35 ml water and shake the mixture. To this solution add 4 g sodium hydroxide pellets in small portions with
constant swirling (Note I). After the addition is complete attach a reflux condenser to the flask and reflux the mixture gently for 40 min. Cool and pour the contents in a beaker containing 200 ml of cold water. Filter to remove any unchanged benzophenone. Acidify the filtrate with dil. sulfuric acid to precipitate the oxime. Filter the solid on a Buchner funnel and wash several times with cold water and dry the solid in the oven at 7080 o C. Recrystallize from ethanol. The yield is 3.7 g, m.p. 142o C. Step B: Preparation of benzanilide Procedure: In an Erlenmeyer flask, dissolve 3 g of benzophenone oxime in 30 ml dry ether
Note (II ). To this add 4 ml of thionyl chloride or a few drops of conc. sulfuric acid or 4 g of phosphorus pentachloride. Shake the mixture for 15 min. Remove ether on a water-bath Note(III). Cool the residue and add 35 ml water. Boil for 105 min. Decant the supernatant liquid and recrystallize the remaining solid from hot ethanol. The yield is 2.4 g, m.p. 162oC. Notes I : If the reaction becomes too vigorous cool the flask under the tap. II : Boil off ether on a water-bath in a fume hood. III : Only sodium dry ether should be used.
8.4 THE PERKIN REACTION The Perkin reaction is used for the preparation of unsaturated compounds, particularly unsaturated carboxylic acids. In this reaction an aromatic aldehyde is condensed with acid anhydride in the presence of sodium or potassium salt which functions as a catalyst.
8.4.1 Preparation of Cinnamic Acid Benzaldehyde is condensed with acetic anhydride in the presence of potassium acetate, followed by hydrolysis. This reaction is useful for the preparation of unsaturated carboxylic acids.
Procedure: Place 10.5 g (10 ml ) of benzaldehyde, 14 ml of acetic anhydride and 6 g of freshly fused sodium acetate (Note I ) in a 200 ml round-bottomed flask. Reflux the mixture
188
LABORATORY MANUAL OF ORGANIC CHEMISTRY
in an oil-bath at 170180oC for 90 min. Foaming occurs initially because of the evolution of carbon dioxide. Cool the flask and add 75 ml of water followed by the addition of 10% sodium hydroxide solution till alkaline. Extract the clear solution with two 35 ml portions of ether to remove any unchanged benzaldehyde. Acidify the aqueous layer with conc. hydrochloric acid until no more carbon dioxide evolves. Filter off the precipitated solid on a Buchner funnel at the pump, wash with water and recrystallize from hot water. The yield is 8.5 g, m.p. 133oC. Note I: Do not use sodium hydroxide a strong base, otherwise the Cannizzaro reaction will take place.
8.5 THE CANNIZZARO REACTION The Perkin reaction is a base-catalyzed oxidation-reduction reaction. In this reaction an aldehyde having no a-hydrogen is treated with acetic anhydride in the presence of potassium hydroxide which acts as a catalyst. If two moles of benzaldehyde are taken, one mole is oxidized to acid and the other is reduced to an alcohol. It is a reaction often used for the preparation of benzyl alcohol. Benzoic acid present as its sodium salt is soluble in water. Benzyl alcohol is insoluble in water and thus can be easily separated from the mixture.
8.5.1 Base-Catalyzed Oxidation-Reduction of Benzaldehyde Aromatic aldehydes are the most common type of compounds which undergo the Cannizzaro reaction. Benzaldehyde in the presence of a strong base forms benzyl alcohol and benzoic acid.
Proceduce: In a 200 ml round-bottomed flask dissolve 12.5 g of potassium hydroxide pellets
in 65 ml water. To the solution add 21.1 g (20 ml) of distilled benzaldehyde. Attach a condenser and reflux the mixture for 1 hr. Cool the flask and add just sufficient water to dissolve any precipitated sodium benzoate. Transfer the mixture to a separatory funnel and extract thrice with 25 ml portions of ether. Save the lower aqueous layer. Wash the combined ether extracts with aqueous sodium bisulfite
( 20% )
solution to remove unchanged
benzaldehyde. Now wash with water and dry the ethereal solution (MgSO4) . Remove ether in the hood on a hot plate and distil the residue and collect benzyl alcohol at 204207°C. The yield is 5.9 g. Take 30 ml conc. hydrochloric acid, 30 ml water and about 60 g crushed ice in a 400 ml beaker. Pour the above aqueous solution slowly into the acid, stirring it constantly. The acid precipitates. Filter off the solid benzoic acid on a Buchner funnel at the pump and wash with cold water. Recrystallize from boiling water. The yield is 8.8 g, m.p. 121°C.
ORGANIC PREPARATIONS
189
Questions 8.12 By what mechanism would sodium bisulfite remove unchanged benzaldehyde from the reaction mixture? 8.13 Write an equation for the reaction of a mixture of benzaldehyde and formaldehyde with conc. sodium hydroxide solution.
8.6 THE FRIES REARRANGEMENT The rearrangement of phenolic esters in the presence of anhydrous aluminum chloride on heating into isomeric hydroxy ketones is called the Fries rearrangement. Phenyl creatate under these conditions is converted into 2- and 4- hydroxyacetophenones. The mixture can be separated by steam distillation.
8.6.1 Preparation of 2, 5-Dihydroxyacetophenone This preparation will be carried out in two steps:
Step A: Preparation of hydroquinone diacetate Procedure: Place 5.5 g of hydroquinone and 10 g of freshly distilled acetic anhydride in a 100 ml dry Erlenmeyer flask. Add 2 drops of conc. sulfuric acid. Shake the flask for 10 min.
190
LABORATORY MANUAL OF ORGANIC CHEMISTRY
Pour the mixture onto 40 g of ice, taken in a beaker. Collect the solid on a Buchner funnel. Recrystallize from hot aqueous ethanol. The yield is 9 g, m.p. 122o C. Step B: Preparation of 2, 5-dihydroxyacetophenone Procedure: In a 100 ml round-bottomed flask, place 4 g powdered hydroquinone diacetate weigh 8.5 g anhyd. aluminum chloride. Grind in a pestle and mortar and immediately add to the flask. Attach an air condenser filled with a drying tube and heat the flask between 115120o C in an oil-bath in the fume hood for 30 min. After this duration, raise the temperature to 150oC. When the evolution of hydrochloric acid gas commences heat at this temperature for 1 hr. Cool the flask, add 50 g of crushed ice and 4 ml conc. hydrochloric acid and swirl. Collect the solid on a Buchner funnel and wash it with cold water. Recrystallize from aqueous boiling ethanol. The yield is 1.8 g, m.p. 202203o C.
Question 8.14 Discuss the mechanism of the Fries rearrangement.
8.7 THE SCHÖTTEN-BAUMANN REACTION This reaction is used for the benzoylation of aromatic amines using benzoyl chloride and aqueous sodium hydroxide solution. Since an amine is more soluble in acid chloride than in sodium hydroxide, reaction occurs preferentially between benzoyl chloride and the amine. Phenols can similarly be benzoylated. In this reaction the function of the base is not clear. It seems not only to neutralize the hydrochlorid acid that would otherwise be liberated, but also to catalyse the reaction. This reaction should be carried out in the fume hood.
8.7.1 Preparation of Benzanilide For benzanilide preparation aniline is treated with benzoyl chloride in the presence of sodium hydroxide solution.
Procedure: In a 100 ml Erlenmeyer flask place 2.6 g (2.5 ml ) of aniline and 25 ml of 10% aqueous sodium hydroxide solution. To this add 4.3 g (3.5 ml) of benzoyl chloride in small portions with vigorous shaking for 1 min after every addition. Cork the flask and shake vigorously for 10 min. The reaction is exothermic and the flask becomes hot. Benzoyl
derivative may separate out as a white powder when the reaction is complete ( Notes I and
ORGANIC PREPARATIONS
191
II). Filter the solid on a Buchner funnel at the pump. Wash several times with water and drain. Recrystallize from boiling alcohol. The yield is 4.4 g, m.p. 162oC. Notes I: This can be established when the reaction mixture no longer smells of benzoyl chloride. II: At this point make sure that the reaction mixture is alkaline.
Question 8.15 Why is an aromatic acid chloride less reactive than the aliphatic acid chloride in the Schötten-Baumann reaction?
8.8 BENZILIC ACID REARRANGEMENT Benzoin, an a-hydroxy ketone obtained from benzaldehyde by the benzoin condensation is oxidized by nitric acid to benzil, an a, b-diketone. This in the presence of patassium hydroxide is converted to benzilic acid and the reaction is called benzilic acid rearrangement. This reaction can be carried out by taking benzil.
8.8.1 Preparation of Benzilic Acid Mechanistically benzil, prepared from benzoin, on refluxing with aqueous alc. potassium hydroxide undergoes a skeletal rearrangement to yield benzilic acid according to the following sequence:
The CN ion is a specific catalyst for condensation. The specificity is attributed to many factors. Through for many years it was believed that only cyanide ion can catalyze
the benzoin condensation, however, recently thiamine hydrochloride (Vitamin B 1) has been found to be an effective catalyst as well.
192
LABORATORY MANUAL OF ORGANIC CHEMISTRY
This preparation involves the following three steps. However, the reaction is frequently accomplished by taking benzin. Step A: Preparation of benzoin Procedure: In a 200 ml round-bottomed flask, place 12.5 g benzaldehyde, 25 g potassium
cyanide (Note I) and add 25 ml ethyl alcohol. Reflux the mixture for 30 min in the hood. Cool the flask and filter the crude benzoin on a Buchner funnel at the pump. Wash thoroughly with cold water and dry. The yield of benzoin is 10.5 g, m.p. 137oC. Step B: Preparation of benzil
Procedure: Place 5.0 g benzoin and 25 ml conc. nitric acid in a 100 ml round-bottomed flask. Equip the flask with an air condenser and heat on a water-bath for 1 hr or till the evolution of the oxides of nitrogen ceases. Pour the contents of the flask in 100 ml of cold water taken in a beaker. A crystalline yellow mass separates out. Collect the solid on a Buchner funnel and wash thoroughly with cold water. Recrystallize from alcohol. The yield is 4.8 g, m.p. 9496o C. Step C: Preparation of benzilic acid Procedure: Place 3 g of benzil in a 100 ml round-bottomed flask and to this add a solution of 3 g of potassium hydroxide in 10 ml of water. Also add 7 ml of ethanol and shake to obtain a bluish-black solution. Replace the water condenser and reflux the mixture on a waterbath for 15 min. Transfer the contents to a China dish and cool it in an ice-bath for 30 min. The potassium salt of benzilic acid separates out. Filter the solid and wash thoroughly with cold water. Dissolve the salt in 30 ml water and acidify the solution with conc. hydrochloric acid with constant stirring. A red-brown precipitate of the acid is formed. Filter and wash with cold water. Recrystallize from boiling water using some activated charcoal. The yield is 3 g, m.p. 150oC. Note I: KCN is a fatal poison, it should be handled carefully and wisely. This reaction should be performed under the strict supervision of the teacher. This preparation should, prefectly be carried out by taking benzil.
Question 8.16 Would alphatic aldehydes undergo step A?
ORGANIC PREPARATIONS
193
8.9 THE REIMER-TIEMANN REACTION In this reaction phenol is converted to o- and p-hydroxybenzaldehydes in the presence of chloroform and sodium hydroxide.
8.9.1 Preparation of Salicylaldehyde An isomeric mixture, in which salicylaldehyde is the major product is obtained from phenol, chloroform and sodium hydroxide. A dichlorocarbene is generated initially from chloroform by the action of base which attacks the benzene ring.
Procedure: In a 250 ml round-bottomed flask fitted with a water condenser and a thermometer, place 20 g sodium hydroxide and dissolve in 20 ml water. To this add a solution of 6.2 g of freshly distilled phenol in 7 ml water. Mix the contents. Heat the flask on a water-bath so that the temperature remains below 6065o C ( Note I ) . Add 15 g
(10.2 ml) of chloroform in small portions over a period of 10 min from a dropping funnel
with efficient stirring. Maintain the temperature below 6065oC by heating or cooling the bath as necessary. Use a thermometer. Heat the mixture on a water-bath for 30 min. Steam distil the mixture to remove unreacted chloroform. Allow the flask to cool and an
194
LABORATORY MANUAL OF ORGANIC CHEMISTRY
orange-red liquid remains in the flask. Acidify it with dil. sulfuric acid carefully and steam distil the mixture again until no more oily drops of salicylaldehyde pass over. The residue in the flask contains p-hydroxybenzaldehyde. Extract the distillate with ether twice to obtain salicylaldehyde as well as some unreacted phenol. Remove ether on a hot water-bath in a hood and transfer the remaining liquid to a separatory funnel and add twice the amount of a saturated solution of sodium bisulfite and shake vigorously for 30 min. Then clamp the separatory funnel on an iron-stand and allow it to stand for 1 hr. Filter the bisulfite adduct on a Buchner funnel. Wash it with a little alcohol and then with ether to remove any phenol. Take the bisulfite compound in a beaker, add dil. sulfuric acid and warm on a water-bath. Cool and extract salicylaldehyde with ether and distil. The product distils between 19597oC. The yield is 2.4 g. To obtain p-hydroxybenzaldehyde (by-product) filter the residue while hot through a filter paper and cool. Extract with ether and remove the solvent on a hot water-bath. Recrystallize the crude solid so obtained from boiling water. The yield is 0.55 g, m.p. 116o C. Note I: The temperature of the bath may be adjusted by cooling or heating as is deemed essential.
8.10 OXIDATION AND REDUCTION Several types of oxidizing and reducing agents are employed in organic syntheses. Their use will be illustrated in the preparation of some compounds.
8.10.1 Preparation of Cyclohexanone (Oxidation) Oxidation of sodium dichromate is a common method for the oxidation of a secondary alcohol to ketone. In this preparation, cyclohexanone is obtained by the oxidation of cyclohexanol.
Nascent oxygen is the active oxidizing opecies and is available according to the following reactions:
Procedure: In a 250 ml Erlenmeyer flask, place 20.5 g Na2Cr2O7.2H2O, 100 ml water and add carefully 9.5 ml conc. sulfuric acid. Shake and cool the resulting orange-red solution of chromic acid to 15o C. In a second Erlenmeyer flask, take 10 g of cyclohexanol and cool this
195
ORGANIC PREPARATIONS
also to 15o C. Use a thermometer. Pour the dichromate solution in one lot to the flask containing cyclohexanol. Shake the flask vigorously. Since the reaction is exothermic and if the temperature rises above 60oC, cool it in an ice-bath (Note I ). When the temperature stops rising allow the flask to stand for 30 min at room temperature. Transfer the reaction mixture to a 250 ml round-bottomed flask, add 100 ml of water, a few pieces of boiling stones and distil without using a thermometer. Distil the mixture until 70 ml of the distillate has collected. Place the distillate in a separatory funnel and shake with a saturated solution of sodium chloride. Collect the upper organic layer. Wash the aqueous layer with 20 ml of ether. Combine the extract with the organic layer and dry (Na 2SO4). Filter and remove ether on a water-bath in a hood. Distill the residue and collect the fraction between 154156 o C. The yield is 6.6 g. Note I: The temperature should not fall below 55 oC or rise above 60 oC.
8.10.2 Preparation of p-Nitrobenzoic Acid (Oxidation) The oxidation of toluene to benzoic acid is extremely slow and cannot be completed in the limited laboratory period. If a nitro group is introduced at the para position, the oxidation of the methyl group is achieved readily.
Procedure: Charge a 250 ml round-bottomed flask with 6.2 g of p-nitrotoluene, 17 g of sodium dichromate (Na Cr O . 2 H O) and 40 ml of water. Add 21 ml of conc. sulfuric acid 2
2
7
2
dropwise to the flask shaking while adding. An exothermic reaction commences, cool the flask under the tap from time to time. When the addition of the acid is complete, reflux the mixture gently for 15 min on a wire gauze. Allow the flask to cool then pour the contents in a beaker containing 40 ml of water. Collect the crude acid on a Buchner funnel and wash twice with water. Transfer the solid from the funnel to a 400 ml beaker and add 20 ml of 5% sulfuric acid. Digest the contents of the beaker on a water-bath for 20 min with frequent stirring with a glass rod for the removal of chromium salt. Allow the beaker to cool and filter again. Dissolve the acid in 50 ml of 5% sodium hydroxide solution and filter to remove any chromium hydroxide and unchanged p-nitrotoluene. Wash the filtrate on a Buchner funnel thoroughly with cold water. Recrystallize from hot benzene. The yield is 5.2 g, m.p. 237oC.
196
LABORATORY MANUAL OF ORGANIC CHEMISTRY
Question 8.17 Would it be possible to attempt preparation of benzaldehyde by permanganate oxidation of toluene?
8.10.3 Preparation of Anthraquinone (Oxidation) Though benzene is very much resistant to oxidation, anthracene can be easily oxidized to 9, 10-anthraquinone using a mixture of sodium dichromate and conc. sulfuric acid.
Procedure: Place 5 g of crystallized anthracene and 50 ml of glacial acetic acid in a 500 ml round-bottomed flask fitted with a reflux condenser. Boil the solution on a Bunsen burner and slowly add a solution of 13 g sodium dichromate prepared in a mixture of 15 ml water and 5 ml conc. sulfuric acid. Place a dropping funnel at the top of the reflux condenser containing 35 ml of glacial acetic acid, add it dropwie to the flask over a period of 15 min. Keep the temperature of the reaction mixture at the boiling point. After the addition is complete, boil for an additional period of 20 min. Cool the flask to allow the separation of solid anthraquinone. Filter and wash the solid with 20 ml of 70% solution of acetic acid and then with cold water. Recrystallize from dil. acetic acid. The yield of anthraquinone is 5.2 g, m.p. 285286oC.
8.10.4 Preparation of Adipic Acid (Oxidation) Adipic acid is obtained by the direct oxidation of cyclohexanol with conc. nitric acid used as an oxidizing agent. In this reaction cyclohexanol is oxidized to cyclohexanone initially which is immediately converted to adipic acid.
Procedure: Fit a 500 ml three-necked flask equipped with a small dropping funnel, a thermometer and an exit tube needed to exit the evolved oxides of nitrogen over the surface
ORGANIC PREPARATIONS
197
of a 50 ml 10% sodium hydroxide contained in a large bottle. Place 20 ml of conc. nitric acid
(d 1.42 ) in the flask and dilute it with 10 ml of water. Take 4 ml of cyclohexanol in the
dropping funnel. Heat the diluted acid to about 85o C and add one drop of cyclohexanol at a time from the dropping funnel. A highly exothermic reaction commences immediately,
when the temperature has fallen to 80o C, add another drop of cyclohexanol (Note I). The addition of cyclohexanol is usually complete in 1520 min. Finally warm the contents of the flask to 99100oC for 5 min and then cool in an ice-bath, adipic acid crystallizes out. Filter the adipic acid under suction and wash with cold water. Recrystallize the acid from a minimum amount of hot water. Filter again and wash with cold water. The yield is 3.1 g, m.p. 152oC. Note I: Do not attempt to add fresh drop of cychlohexanol until the previous one has reacted. Moreover, do not allow any cyclohexanol to accumulate in the flask otherwise an almost violent explosion may take place.
8.10.5 Preparation of Benzoic Acid (Oxidation) Acetophenone cannot be oxidized to benzoic acid by the usual oxidizing agents. For ketones in which one group is methyl, can instead be oxidized by the haloform reaction. Acetophenone in treated with bromine and sodium hydroxide solution whereby benzoic acid and bromoform a liquid are formed in the reaction.
Procedure: Bromine solution is first prepared. In a 250 ml round-bottomed flask, dissolve 1 g of sodium hydroxide in 50 ml of water. To this solution add 40 g of crushed ice. Take the
flask to the fume hood (Note I) and add 2 ml of bromine and shake the flask until bromine dissolves. Add 2 ml of acetophenone dropwise and shake the flask for 10 min. Transfer the contents of the flask to a separatory funnel and withdraw the lower layer of bromoform.Transfer the liquid into a beaker, add about 0.5 g of activated carbon, stir and filter. To the filtrate, add some crushed ice and acidify with dilute sulfuric acid. The solution often has a yellowish orange color at this stage due to the presence of excess bromine. This color can be removed by adding dropwise a solution of sodium bisulfite. Filter again and recrystallize benzoic acid from boiling water. Yield 6.2 g, m.p. 122oC. Note I: With bromine always work in the fume hood.
198
LABORATORY MANUAL OF ORGANIC CHEMISTRY
Question 8.18 What type of ketones are oxidized by sodium hypobromite?
8.10.6 Preparation of Trimethylacetic Acid (Oxidation) Pinacolone on oxidation with sodium hypobromite forms trimethylacetic acid, also known as pivalic acid.
This acid alternatively can also be obtained from Grignard reaction by carbonation of t-butyl chloride followed by protonation of the intermediate complex.
Procedure: Dissolve 40 g sodium hydroxide in 75 ml water in a 500 ml Erlenmeyer flask and cool in ice. Also add 75 g crushed ice. Take the flask to the hood and add 48 g (16.0 ml) of bromine in portions of about 1.0 ml at a time and shake the flask after each addition and wait till all the bromine has dissolved before adding the next lot. Remove the flask from the
ice-bath and add 10 g (12.5 ml) pinacolone over a period of 5 min. Shake the flask and then pour the mixture into a three-necked flask fitted with two dropping funnels. Heat the flask
on a burner till the solution starts boiling and bromoform ( CHBr3) separates out. As soon as the exothermic reaction ceases, distil off the bromoform into a receiver cooled in ice. Collect about 40 ml of the distillate and separate bromoform in a separatory funnel. The yield is 5 ml, b.p. 150oC.
ORGANIC PREPARATIONS
199
Place 35 ml cold conc. sulfuric acid in 50 ml of water into the larger dropping funnel. In the second funnel place 10% sodium thiosulfate solution. Cool the contents of the flask to around 70oC then add sulfuric acid slowly. Because of the presence of excess hypobromite solution, evolution of bromine takes place as the mixture in the flask is acidified. When the red color of bromine appears, stop adding acid and run in some sodium thiosulfate solution. Continue the process of alternate addition of acid and thiosulfate solutions. After the addition is over the solution should be acidic to litmus. At this stage the solution is colorless and trimethylacetic acid separates out as an oil. Distil the mixture and collect the acid which distils over with water. Collect about 75 ml of the distillate, separate the acid in a separatory funnel. The yield is 56 ml, b.p. 164o C/760 mm.
8.10.7 Preparation of Ethylbenzene (The Wolff-Kishner Reduction) Direct reduction of a carbonyl group to a methylene group requires the use of certain special reagents. Such a reduction has been accomplished by the Clemmensen reduction or by the RaNi reduction of thioketal. These reactions suffer from certain drawbacks. The Clemmensen reduction, for instance, is subject to steric hindrance by the presence of neighbouring substituents. An indirect method of reduction of carbonyl to methylene is known as the Wolff-Kishner reduction. Originally the method involved two steps, first forming a hydrazone of the carbonyl compound and second heating the performed hydrazone with sodium ethoxide in a tube. Nowadays, the Huang-Minlon modification is found more convenient. According to this a mixture of carbonyl compound, hydrazine hydrate and potassium hydroxide are heated in a high boiling solvent such as diethylene glycol*. Then the two steps are carried out in a single step. This modification is used in the present preparation.
The reaction has the following mechanism:
*Alternatively, triethylene glycol (b.p. 278°C) (HOCH2 CH2 O CH2 CH2 O CH2 CH2 OH) may be used.
200
LABORATORY MANUAL OF ORGANIC CHEMISTRY
Procedure: In a 200 ml round-bottomed flask, place 9 g of pure acetophenone, 60 ml diethylene glycol
(b.p. 245oC) 10 g potassium hydroxide and 8 ml of 90%
hydrazine hydrate. Add 23 boiling chips. Heat the mixture on a water-bath till most of the potassium hydroxide has dissolved. Attach a water condenser to the flask and reflux on the flame for 1 hr. After this period remove the condenser and distil off most of the water and hydrazine until the temperature of the liquid rises to 200oC (Note I) and collect the distillate. Separate the organic layer in a separatory funnel. Extract the aqueous layer twice with ether. Combine the organic layer and the extracts, dry over anhydrous sodium sulfate. Remove ether and distil the residue and collect the fraction between 134137 oC. The yield is 5.8 g. Note I: Use a thermometer.
8.10.8 Preparation of Benzhydrol (Reduction) Reduction of benzophenone with zinc dust and alc. sodium hydroxide solution, a mild reducing agent, results in the formation of a secondary alcohol, i.e., benzhydrol.
Procedure: Place 6.3 g benzophenone, 65 ml ethanol, 6.3 g sodium hydroxide and 6.3 g of zinc powder in a 200 ml bolt-head flask. Equip the flask with a reflux condenser. Mix the contents and then warm gently on a water-bath for 1.5 hr. Allow the flask to cool to 60o C and then filter the reaction mixture by suction. Wash the residue on the filter paper twice with 5 ml portions of ethanol. Pour the clear filtrate in 250 ml cold water and acidify with 25 ml of conc. hydrochloric acid. A viscous oil separates out which solidifies on cooling or keeping overnight. Filter the solid under suction and recrystallize from 10 ml of hot ethyl alcohol. The yield is 3.9 g, m.pt. 58oC.
8.10.9 Preparation and Stereochemistry of Azobenzene (Reduction) Azobenzene is prepared by reducing nitrobenzene in the presence of a mild reducing agent, i.e., magnesium metal and methyl alcohol.
ORGANIC PREPARATIONS
201
Procedure: In a 250 ml round-bottomed flask equipped with a reflux condenser, place 6.2 g of nitrobenzene and 110 ml of absolute methanol. Add 3 g of a magnesium turnings and a few crystals of iodine. If no reaction takes place, warm the flask. Once the reaction has started no additional heat is necessary. After most of the magnesium has reacted add another 3 g of it and allow it to react completely. Reflux the reaction mixture for 30 min, cool the flask and pour the contents into 200 ml of ice water. Neutralize the alkaline solution
with glacial acetic acid (check with a litmus paper) and cool again. Filter the orange-yellow azobenzene on a Buchner funnel. Recrystallize it from ethanol. The yield is 3.1 g, m.p. 68oC.
Separation of Isomers Azobenzene displays geometric isomerism and exists in the following syn-and antiforms.
These two forms can be separated by column chromatography and their identity is established by ultraviolet spectroscopy. Procedure: Prepare a chromatographic column (Note I) from 10 g of activated alumina and petroleum ether. Dissolve 1 g azobenzene ( Note II) in a minimum amount of ether and apply to the column.
Elute the column with 150 ml of petroleum ether (boiling range 3060o C) . As the solvent runs through the column, a broad orange band of anti-isomer should be observed to move slowly down the column. A yellow narrow band of syn-isomer should remain very near the top of the column. Collect only one fraction in an Erlemeyer flask wrapped in
aluminum foil (Note III) . Now elute the column with a solvent mixture of petroleum ether and 1% methanol, and collect the fraction. Evaporate the solvent from both the fractions on a steam-bath and take the u.v. spectrum in ethanol. The first fraction shows lmax = 321 corresponds to the anti-isomer while the second fraction as a lmax = 280 and is the synisomer. Notes I: Put a glass wool plug at the bottom of a 25 ml burette. Now pour 20 ml of pet ether in the burette and add 10 g of alumina from the top in a continuous stream. The burette should be maintained in a vertical position and clamped on an iron-stand. Then add a layer of sand and drain off the solvent till its lavel is about 2 cm above the level of packing. II: Do not use an old sample of azobenzene. III: Alternatively carbon paper can be wrapped.
202
LABORATORY MANUAL OF ORGANIC CHEMISTRY
8.10.10 Preparation of m-Nitroaniline from m-Dinitrobenzene (Reduction) m-Dinitrobenzene is selectively reduced by sodium bisulfite to obtain m-nitroaniline.
The preparation is carried out in two steps: Step A: Preparation of m-dinitrobenzene Proceduce: In a 100 ml round-bottomed flask, place 11.3 g (7.5 ml) of fuming nitric acid, to this slowly add 18.4 g ( 10.5 ml) of conc. sulfuric acid. Fit the flask with a reflux condenser and through it, add 7.5 g (6.3 ml) of nitrobenzene in four small portions with thorough shaking. After the addition is complete reflux the mixture on a water-bath in a fume hood for 15 min. With frequent shaking, cool and pour the contents into 200 ml of cold water taken in a 600 ml beaker. The product separates out as a pale yellow solid. Filter on a Buchner funnel and wash thoroughly with cold water to remove the acid. To purify mdinitrobenzene, take the crude product in a 100 ml round-bottomed flask with 40 ml of ethanol and reflux on a water-bath till all the solid has dissolved. Filter the hot solution and allow the filtrate to cool. Separate the solid by suction and dry. The yield is 7.2 g, m.p. 8990oC. Step B: Preparation of m-nitroaniline Procedure: In a 250 ml Erlenmeyer flask dissolve 15.0 g of sodium bisulfite (Na 2S. 9H 2O) in 30 ml of water and to the solution add 5.0 g of powdered sodium bicarbonate in small portions with constant stirring. Then add 40 ml of methanol and cool the mixture to 20o C. Filter to remove the precipitated sodium carbonate and wash the solid with a little methanol. The filtrate contains sodium bisulfite (NaHS) solution needed for reduction. Transfer 5 g of m-dinitrobenzene in a 250 ml round-bottomed flask, add 45 ml of methanol and warm. To this add sodium bisulfite solution prepared above. Fix a reflux condenser to the flask and reflux for 20 min (Note I) . Allow the flask to cool and distil most of methanol from a water-bath. Pour the residue from the distilling flask into a beaker and keep stirring. Collect the yellow m-nitroaniline on a Buchner funnel and wash with water. Recrystallize from 75% methanol. The yield is 3.1 g, m.p. 114oC. Note I: Some sodium carbonate may also precipitate at this stage, ignore it.
8.10.11 Reduction of p-Nitroacetophenone (Selective Reduction) Sodium borohydride is a mild reducing agent while lithium aluminum hydride is a powerful reducing agent. Lithium aluminum hydride reduces most functional groups. It is used in dry solvents as it reacts violently with water. Sodium borohydride, on the other hand, is a
ORGANIC PREPARATIONS
203
mild reducing agent and exhibits considerable selectivity. It reduces aldehydes and ketones rapidly. Other functional groups such as
, etc. are either slowly
reduced or are inert. This reagent is used in ethanol or methanol. In the following experiment p-nitroacetophenone in reduced is p-nitro-1-phenyl-1-ethanol using sodium borohydride.
Reduction of benzophenone to benzhydrol of experiment (8.10.8) can also be carried out using sodium borohydride. Procedure: Dissolve 2.2 g p-nitroacetophenone in 28 ml ethanol by warming in an Erlenmeyer flask. Cool the solution in ice to produce a fine suspension of solid. In a test tube dissolve 0.69 sodium borohydride in 1 ml of water and add to the reaction mixture dropwise completing in 30 min. During this time a slight decolorization takes place. Pour the mixture in a beaker containing 20 ml water and 1 ml of concentrated hydrochloric acid. After a few minutes transfer the contents to a separatory funnel and extract twice with 30 ml portions of ether. Dry the combined extracts over anhyd. sodium sulfate. Remove ether on a hot plate to obtain a light brown oil. The p-nitrophenylmethylcarbinol is distilled under reduced pressure, b.p. 1613 oC/4 mm.
Questions 8.19 Write the products obtained by the reduction of m-nitroacetophenone with Sn/HCl and NaBH4 respectively. 8.20 What other reagents besides NaBH4 will reduce acetophenone to 1-phenyl-1-ethanol?
8.11 ORGANOMETALLIC CHEMISTRY Organometallic compounds probably represent one of the single most useful synthetic tools for the preparation of organic compounds. In an organometallic compound, a metal atom is
linked directly to an organic group ( R M ). The bond formed has a high degree of ionic character.
8.11.1 Preparation of Benzoic Acid (The Grignard Reaction) A Grignard reagent has the general formula RMgX. Such reagents are highly reactive and have proven to be of great synthetic utility.
204
LABORATORY MANUAL OF ORGANIC CHEMISTRY
Benzoic acid can be prepared by treating phenyl magnesium bromide (the Grignard reagent) with carbon dioxide and subsequent hydrolysis of the complex.
Procedure: In a 250 ml round-bottomed flask fitted with a reflux condenser, place 2.4 g of dry magnesium turnings in 30 ml of sodium dry ether. To this add slowly 15.7 g (10 ml) of
dry bromobenzene (Note I) and a crystal of iodine. There is an immediate commencement of reaction with ether appearing milky white. If, however, the reaction does not start, warm the flask on a water-bath and remove it after the mixture starts refluxing. This will usually promote the reaction. The reaction subsequently will start itself, boil for 3540 min. After this heat the flask in a beaker of warm water for an additional period of 10 min. Place approximately 15 g of crushed dry ice in a 250 ml beaker and pour into it slowly the Grignard reagent prepared above, with constant stirring. A vigorous reaction ensues and the contents in the flask turn into a pasty mass. Stir it till all the carbon dioxide has evaporated. Add 50 ml of warm water and then acidify the contents with dil. hydrochloric acid in order to generate benzoic acid as well as dissolve the magnesium salt. Cool the beaker in ice and filter. Recrystallize from hot water, yield 6.0 g, m.p. 122oC. Note I : Bromobenzene may be dried over anhydrous calcium chloride.
Question 8.21 Suggest three additional methods for the preparation of benzoic acid.
8.11.2 Preparation of Triphenylmethanol (The Grignard Reaction) Extremely dry conditions are necessary for its preparation. The reaction may preferably be performed under an atmosphere of nitrogen.
ORGANIC PREPARATIONS
205
Procedure: In a 250 ml three-necked flask equipped with a mechanical stirrer, a water condenser, a drying tube and a dropping funnel, place 2.7 g of magnesium turnings in 20 ml sodium dry ether. Also add a crystal of iodine. From the dropping funnel add slowly a solution of 18 g of bromobenzene in 50 ml of dry ether with constant stirring. An exothermic
reaction ensues (Note I). When the addition of bromobenzene is complete reflux the mixture for 5 min to complete the formation of Grignard reagent. Cool the flask in cold water, and add to it a solution of 7.5 g benzophenone in 25 ml of ether taken in the dropping funnel. Reflux for 1015 min on a water-bath. Cool the flask again and pour the contents in a beaker containing 200 g of ice and 60 ml of 20% sulfuric acid. Stir the mixture with a glass rod to decompose the magnesium compound. Transfer to a separatory funnel, discard the aqueous layer. Wash the organic layer with 25 ml of 10% sulfuric acid and then with water. Steam distil the mixture till no more oil passes over. Cool the distillation flask and recrystallize the residue from methanol or benzene. The yield is 8.4 g, m.pt. 160162oC. Note: If the reaction does not commence, warm the flask slightly. Appearance of turbidity indicates the occurrence of the reaction.
Question 8.22 Why are absolutely dry conditions necessary for this reaction?
8.11.3 Preparation of p-Toluic Acid from p-Bromotoluene Organolithium compounds analogous to the Grignard reagents yield carboxylic acids on carbonation. An organolithium compound can be prepared by the replacement of the halo atom of an organic halide by lithium in dry ether under an atmosphere of nitrogen. The resulting organolithium is carbonated with dry ice and subsequently hydrolyzed to yield the acid. This process is demonstrated for the preparation of p-toluic acid from p-bromotoluene.
Procedure: In a 250 ml three-necked fitted with a reflux condenser, mercury seal, stirrer and a small dropping funnel combined with a glass inlet, place 20 ml of anhydrous ether and
flush the flask with dry nitrogen gas. Add 0.95 g of lithium metal (Note I) in the form of shavings and stir. Take a solution of 10.8 g of p-bromotoluene in 20 ml of dry ether in the dropping funnel. Add about 1 ml of this solution into the flask. An exothermic reaction commences immediately because lithium reacts more rapidly with organic halide than magnesium does. Add the remaining solution slowly within a period of 15 min with constant
206
LABORATORY MANUAL OF ORGANIC CHEMISTRY
stirring and simultaneous passage of nitrogen gas. Reflux the resultant solution on a waterbath for 2530 min to complete the reaction. Cool the flask in an ice-bath, dilute with 25 ml of ether and cool again to 50°C with the acid of acetone dry ice mixture. In a 500 ml beaker take 200 g of crushed dry ice and 50 ml ether and stir. To this add slowly the solution of lithium derivative of p-bromotoluene. Rinse the flask with a small quantity of ether and pour into the beaker. Allow the mixture to stand at room temperature for 23 hrs for complete evaporation of dry ice. After this period add 100 ml of water. At this point a solid may appear which dissolves on standing. To this add 20 ml of ether and transfer the contents to a separatory funnel, shake and withdraw the aqueous layer. Wash the aqueous layer twice with ether. Save the extract in a beaker. Shake the remaining aqueous layer with 25 ml of 10% sodium hydroxide solution to obtain the acid as its sodium salt. Heat on a waterbath to drive off the dissolved ether and then cold the solution to 5oC, and strongly acidify with conc. hydrochloric acid to separate p-toluic acid. Collect the solid on a Buchner funnel, wash with cold water and dry. Recrystallize the acid from hot ethanol. The yield is 5.1 g, m.pt. 176177oC. A by-product, namely, di-p-tolylketone is also obtained which can be easily separated from the main product. Dry the combined ether extract over anhydrous megnesium sulfate and remove ether over a water-bath. Recrystallize the residue from hot alcohol, yield 1.8 g, m.pt. 95o C.
8.12 DEHYDRATION Alcohols, acids, oximes, etc. can be made to lose a molecule of water under the action of different types of catalysts. The result is the formation of an unsaturated product.
8.12.1 Preparation of Cyclohexene Dehydration of alcohols requires an acidic catalyst to protonate the hydroxyl group of the alcohol and convert it into a good leaving group. A OH group by itself is a poor leaving group. An equilibrium is established between the reactants and the products:
Therefore, in order to drive this equilibrium to the right, it is necessary to remove one or more of the products as they are formed. This can be accomplished either by distilling the products or by adding a dehydrating agent to remove water. In practice, however, a combination of distillation and dehydration is often employed. Cyclohexanol may be dehydrated using either 9 M sulfuric acid or 85% phosphoric acid.
ORGANIC PREPARATIONS
207
Alcohol dehydration takes place through E1 mechanism.
Procedure: Introduce 10 ml of 9 M sulfuric acid into a Claisen flask. Add a few boiling
chips. In one opening fit a 50 ml dropping funnel (a separatory funnel may be used) and place 20 g cyclohexanol. Fit the other opening with a fractionating column and a thermometer and attach a Liebigs condenser. Make sure that all the glass stoppers fit tightly to prevent losses due to evaporation. Heat the flask in an oil-bath at 160170oC. From the dropping funnel add cyclohexanol dropwise over a period of 45 min. After the addition is complete,
raise the temperature to 190200oC (Note I) and distil. The temperature at the top of the column should remain below 90°C. Transfer the distillate to a separatory funnel and shake with saturated sodium chloride solution. Discard the lower layer. Take the upper layer and dry (MgSO4) . Distil the crude cyclohexene from a 10 ml distilling flask and collect the fraction passing over at 8183oC. The yield is 13 g. The residue remaining in the distillation flask is largely unreacted cyclohexanol. Notes I: 85% phosphoric acid is less efficient and gives less yield. II: Use a thermometer.
Questions 8.23 What other side-products may be formed in the above reaction? 8.24 Write the dehydrohalogenation product.
208
LABORATORY MANUAL OF ORGANIC CHEMISTRY
8.12.2 Preparation of Succinic Anhydride Succinic acid dehydrates on heating with acetic anhydride to yield succinic anhydride.
Procedure: Place 7.5 g of succinic acid in a dry 100 ml round-bottomed flask fitted with a reflux condenser and a drying tube. To this carefully add 12.5 ml of acetic anhydride and heat the mixture on a steam-bath with occasional shaking until a clear solution is obtained. Heat for an additional period of 30 min. Then cool the flask in an ice-bath. Collect the
crystals on a Buchner funnel at the pump and wash with ether (Note I ). The yield is 5.2 g, m.p. 119120oC. Note I: Test the product with cold sodium bicarbonate solution for the presence of unchanged succinic acid.
8.12.3 Dehydration of Camphor Oxime (Molecular Rearrangement) Dehydration of camphor oxime under the Beckmann conditions offers an interesting example of a skeletal rearrangement. The oxime does not produce the usual N-substituted amide, but a nitrile. Mechanistically its formation can be shown as below:
This reaction is carried out in two steps:
209
ORGANIC PREPARATIONS
Step A: Preparation of camphor oxime Procedure : In a 250 ml Erlenmeyer flask place a mixtue of 3 g of camphor, 3 g hydrazine hydrochloride, 3.5 ml of pyridine and 25 ml of ethanol. Shake and warm the flask on a steam-bath for 1 hr. Then distil ethanol under vacuum of an aspirator. Add 25 ml of water to the residue, swirl and filter the solid on a Buchner funnel. Wash the product with 10 ml of cold water. The oxime is obtained in a yield of 2.5 g, m.p. 118119o C. Step B: Dehydration of camphor oxime Procedure: Take 2 g of dry camphor oxime in an Erlenmeyer flask and cool it in an icebath. Then add 1.4 g of freshly distilled acetyl chloride in small lots, shaking the reaction mixture constantly. After the addition is complete, allow it to cool to room temperature. Pour the contents into 50 ml of ice water. Transfer to a separatory funnel and extract the resulting nitrile with a mixture of 10 ml of benzene and 10 ml of sodium bicarbonate solution. Withdraw the organic layer. Wash with water and dry over sodium sulfate. Filler and distil off benzene from a hot water-bath. Transfer the viscous oil to a distillation flask and distil at reduced pressure. The nitrile is obtained as a colorless liquid. The yield is 1.3 g, b.p. 130 132o C/37 mm.
8.13 OPTICAL ACTIVITY Compounds containing an asymmetric carbon atom are optically active, i.e., they rotate the plane of polarized light. The optical rotation of the compound is expressed as a physical constant. It is common to report the specific reaction ( α ) given by the following expression: t
θ
[α ] D = l × c
where
[α]tD is the specific rotation at toC,
θ is the number of degrees through which the
incident beam has been rotated, l ( decimeter) is the length of the sample tube and C is the concentration of solution in g/ml of the solution. The specific rotation is expressed as a dimensionless figure. If the specific rotation of an enantiomer of say menthol is quoted as
[α]20 = + 49.2, the ( +) sign before the value indicates that the plane of incident hight has D been rotated in a clockwise direction, therefore, it is dextrorotatory. The angle of rotation is measured in an instrument called a polarimeter. The instrument consists of a long cylindrical tube containing various parts. A beam of
light (sodium lamp) , emerges plane polarized after passing through the polarizer (a nicol
prism). The light still vibrates in one plane but the plane is tilted due to rotation of the plane of polarization so that it lies at different angle than it did originally. It is then allowed to pass through an analyzer (a second nicol prism). After the light passes through the sample it is no more aligned in a vertical plane and the light is blocked by the analyzer to a certain extent.
210
LABORATORY MANUAL OF ORGANIC CHEMISTRY
In order to allow the polarized light to pass freely, the analyzer must thus be rotated so that it is tilted at the same angle as the emerged polarized light from the sample. For this purpose the analyzer is mounted on a circular dial marked in degrees. The angle of rotation for maximum light to pass through the sample is recorded.
Fig. 8.1 Set up of a polarimeter.
The extent of rotation in terms of specific rotation is calculated with the help of the above expression.
8.13.1 Resolution of Racemic =-Phenylethylamine a-Phenylethylamine may be prepared from acetophenone and ammonium formate. The enantiomers are formed in equal amounts, i.e., a racemic modification is formed. The two optically active forms can be separated by preparing their diastereoisomers and then separating them by standard experimental procedure and finally regenerating the enantiomers. Procedure: Weigh accurately about 5 g of racemic a-phenylethylamine and dissolve in 35 ml of methanol. Determine its specific rotation.
Dissolve 0.028 mole of (+) tartaric acid in 415 ml of methanol in a 1 litre Erlenmeyer
flask by boiling. To the hot solution add the amine solution cautiously (Note I). Add additional a-phenylethylamine to make a total of 0.206 mole of the amine. Allow the solution to stand at room temperature for 24 hrs (Note II). Filter the crystals on a Buchner funnel and wash
them with a small quantity of methanol (Note III) . Dissolve the crystals in about four times their weight of water and slowly add with constant stirring a solution of 8.2 g of sodium hydroxide dissolved in 15 ml water. Extract the resulting mixture four times with 75 ml portions of ether. Combine the ether extracts and wash with 50 ml of saturated sodium chloride solution. Dry the ether solution over magnesium sulfate. Remove ether on a hot plate and distil the residue, (a-phenylethylamine) under aspirator vacuum using a burner because the amine has a b.p. of 9495oC/28 mm. The yield is 5.5 g.
Weigh the amine accurately and dissolve in 35 ml of methanol and measure its specific rotation. The reported specific rotation of the compound is [α ] D = +40.1 20
211
ORGANIC PREPARATIONS
Notes I: Add the amine solution slowly and cautiously to avoid foaming. II: May be kept till the next laboratory period. III: The filtrate contains one isomer.
8.14 HETEROCYCLIC COMPOUNDS Heterocyclic compounds are cyclic compounds in which, in addition to carbon, hetero atoms such as N, S, O, etc. are also present in the ring. The heterocylic rings form a part of many types of natural products. Syntheses of a few heterocyclic compounds will be given here.
8.14.1 Preparation of Quinoline (The Skraup Synthesis) Quinoline is prepared by the Skraup synthesis from aniline, glycerol, sulfuric acid and an oxidizing agent. Nitrobenzene is used as the oxidizing agent in this preparation.
Acrolein
Glycerol is first converted into acrolein by conc. sulfuric acid which subsequently reacts with aniline, followed by oxidation by nitrobenzene to form quinoline. Procedure: Fit a three-necked 250 ml flask with a mechanical stirrer, a reflux condenser and a thermometer. In the flask place 10 g (9.8 ml) of aniline, 15 g glycerol and 400 mg
iodine. Stir the mixture and pour 30 g (16.4 ml) of conc. sulfuric acid slowly down the condenser. An exothermic reaction begins and the temperature rises to 100105o C. Heat the flask gently on an oil-bath at 140 oC. After 15 min raise the temperature to 170 oC and heat for 1 hr. Cool the flask and add 90 ml of 6 N sodium hydroxide solution slowly with
212
LABORATORY MANUAL OF ORGANIC CHEMISTRY
constant shaking. Steam distil the mixture. Distil till no oily drops pass over. Extract the distillate with two 25 ml portions of ether, dry and remove ether on a water-bath. Dissolve the crude product, containing some aniline, in 100 ml of 2.5 N hydrochloric acid in a 250 ml beaker, warm and add 13 g of zinc chloride solution in 22 ml of 2.5 N hydrochloric acid with
constant stirring. Cool the beaker in ice and filter the solid quinoline chlorozincate (Note I) on a Buchner funnel and wash with dil. hydrochloric acid. Transfer the salt to a 250 ml beaker, add 6 ml of water followed by 10% sodium hydroxide solution until the initial precipitate of zinc chloride dissolves completely. Pour the mixture in a separatory funnel and extract quinoline with two 25 ml portions of ether. Dry the combined extracts over anhyd. magnesium sulfate and evaporate ether on a hot water-bath. Distil the residue and collect the fraction distilling between 236238oC. The yield is 6.8 g. Note I: Since quinoline is contaminated with a small amount of aniline, the latter is removed by making its chlorozincate salt which is soluble in water but that of quinoline [(C 9 H7 N)2 ZnCl 4]H2 is insoluble.
8.14.2 Preparation of 2-Phenylindole (The Fischer-Indole Synthesis) This compound is prepared according to the Fischer indole synthesis starting from phenylhydrazine and acetophenone.
The preparation is carried out in the following two steps:
ORGANIC PREPARATIONS
213
Step A: Preparation of acetophenonephenylhydrazone Procedure : In a 100 ml beaker place 6 g of freshly distilled acetophenone and a solution of
5.4 g of phenylhydrazine (Note I) in 20 ml ethanol. To the mixture add 23 drops of glacial acetic acid and heat at 100 o C for 15 min. Cool and filter the solid acetophenone phenylhydrazone. Wash with dil. hydrochloric acid and ethanol, respectively. Recrystallize the product form hot ethanol, m.p. 106oC. Step B: Preparation of 2-phenylindole Procedure: Mix 3 g of the compound prepared in step A with 20 g of polyphosphoric acid
(Note II) in a beaker and heat to boiling for 12 min. Stir with a thermometer maintaining a temperature in the range of 100120°C (Note III). To this add 50 ml of cold water and stir again to dissolve unreacted polyphosphoric acid. Collect the solid on a Buchner funnel, wash with cold water and finally with 5 ml of ethanol. The yield is 2.2 g, m.p. 187o C. Notes I: Phenylhydrazine is very poisonous, if it comes in contact with the skin wash well with water. II: Commercial polyphosphoric acid is difficult to handle because of its high viscosity. It may be prepared fresh by mixing 26 g of phosphorus pentoxide and 14 g of commercial orthophosphoric acid (density = 1.7). III: Use a thermometer.
8.14.3 Preparation of 1-Phenyl-3-Methyl-5-Pyrazolone This compound is formed by heating together ethyl acetoacetate with phenylhydrazine. Phenylmethylpyrozolone is an intermediate in the synthesis of antipyrine.
Procedure: Place 6.4 g of freshly distilled ethyl acetoacetate and 5.4 g of phenylhydrazine in a large test tube or a 100 ml round-bottomed flask. Heat the mixture on a water-bath in a hood with occasional stirring. The clear solution soon becomes turbid due to the formation
214
LABORATORY MANUAL OF ORGANIC CHEMISTRY
of droplets of water. Fit an air condenser and continue heating (135145 oC) for 1 hr. and during this period a heavy reddish syrup separates out. Pour this into a beaker and cool. Stir it with 40 ml of ether. As soon as the crystals separate, cool the beaker in ice and collect the solid on a Buchner funnel. Wash with ether and recrystallize from hot water or alcohol. The yield is 6.5 g., m.p. 127oC.
8.14.4 Preparation of 5-Hydroxy-1, 3-Benzoxazol-2-One p-Benzoquinone and thiourea react in an acidic medium in an addition-cyclization reaction to form the title compound.
The preparation is carried out in two steps: Step A: Preparation of p-benzoquinone.
Procedure: Place 10 g of hydroquinone, 5 g potassium bromate, 5 ml of 1 N sulfuric acid and 100 ml water in a 250 ml bolt-head flask. Fit the flask with a reflux condenser and a thermometer. Heat the mixture slowly to 60 oC on a water-bath. A reddish-brown color starts appearing at 50oC. A clear solution is obtained at 60 oC. After 5 min, heat the reaction mixture to 80°C and maintain this temperature for 10 min with frequent stirring. During this period the reaction mixture turns brownish-yellow. Cool the flask in an ice-bath. Filter the yellow crystals of p-benzoquinone on a Buchner funnel, wash with ice cold water and dry in air. The yield is 7.2 g, m.p. 115.5oC. Step B: Preparation of the final product Procedure: Dissolve 5.7 g thiourea in 35 ml of 2 N hydrochloric acid in a 200 ml round-bottomed flask. To this add 5.4 g p-benzoquinone dissolved in 40 ml glacial acetic acid with constant stirring. After the addition, stir the mixture at room temperature for 30 min during which time a solid separates out. Heat the mixture further on a steam-bath for 1 hr, during which period a clear solution is obtained. Cool the flask in ice-bath till a solid separates. Filter the solid on a Buchner funnel, wash with water and dry. Recrystallize from hot aqueous ethanol. The yield is 9.0 g, m.p. 174175oC.
ORGANIC PREPARATIONS
215
8.14.5 Preparation of 1, 2-Diphenyl-5-Nitrobenzimidazole This compound is prepared by condensing 2-amino-4-nitrophenylamine with benzil (prepared in Section 8.8.1 ) in an acidic medium.
The preparation is carried out in two steps: Step A: Preparation of 2-amino-4-nitrodiphenylamine Procedure: In a 250 ml Erlenmeyer flask, suspend 6 g 2, 4-dinitrodiphenylamine in 50 ml of propanol and conc. ammonium hydroxide solution. Warm the mixture on a steam-bath in
a hood and to the suspension add 18 g sodium sulfide (Na2S.9H2O) in small portions, stirring it continuously. Heat the mixture for an additional period of 30 min and then pour it in 160 ml cold water in a beaker. Immerse the flask in an ice-bath and crystals separate out. Collect the crystals on a Buchner funnel. Dry in air, recrystallize from hot water. The yield is 3.8 g, m.p. 131133o C. Step B: Preparation of 1, 2-diphenyl-5-nitrobenzimidazole Procedure: In a 250 ml Erlenmeyer flask place 2 g of 2-amino-4-nitrodiphenylamine, 2 g of benzil in 40 ml of absolute ethanol and 2 ml conc. hydrochloric acid. Reflux the mixture on a steam-bath for 15 min. Cool and filter the product under suction on a Buchner funnel and wash with cold ethanol. Take 2 g of this intermediate product in a 100 ml round-bottomed flask equipped with a reflux condenser. To this add 12 ml of absolute propanol and 4 ml of conc. hydrochloric acid. Reflux the mixture for 2 hrs. Cool and filter the dark solid on a Buchner funnel. Recrystallize for hot 95% ethanol, use activated charcoal. The yield is 1.5 g, m.p. 181oC.
8.15 DIAZOTISATION The process of forming a diazonium compound from an appropriate primary aromatic amine in the presence of nitrous acid is callled diazotisation. The diazonium compounds are extremely useful in organic syntheses. This is due to the fact that the diazonium group can be replaced by groups such as hydroxy, cyano, halo and hydrogen with great ease. Many compounds that could not be obtained by other means, are easily available through replacement of the diazonium group. The reaction starts by the diazotisation of an amino group of an aniline using sodium nitrite and a mineral acid.
216
LABORATORY MANUAL OF ORGANIC CHEMISTRY
8.15.1 Preparation of p-Iodonitrobenzene In this preparation, p-nitroaniline is diazotised and then treated with KI.
Procedure: In a 250 ml beaker place a mixture of 2.5 g p-nitroaniline, 2 ml conc. sulfuric acid, 15 ml water and stir with a glass rod. Immerse a thermometer in the flask and keep the flask in crushed ice until the temperature lies between 0 and 5o C. In another beaker dissolve 1.3 g of sodium nitrite in 5 ml water and add this solution to the above aniline salt solution slowly with constant stirring and maintaining the temperature below 5 oC ( Note I). Filter the cold solution and add the filtrate to a solution of 5 g potassium iodide in 15 ml of water taken in an Erlenmeyer flask. Filter the solid thus obtained and recrystalize from hot ethanol. The yield is 3.6 g, m.p. 170oC.
Note I: Add a few pieces of crushed ice to the reaction mixture if necessary to maintain the desired temperature.
Question 8.25 Why should the temperature be maintained below 5oC in this preparation?
8.15.2 Preparation of p-Chlorotoluene (The Sandmeyer Reaction) This preparation consists of three steps:
Step A: Preparation of cuprous chloride Cuprous chloride is first prepared by reducing copper sulfate using sodium sulfite in the presence of sodium chloride. +
2−
2Cu2 + 2Cl + SO3 + H2O
2−
2 Cu Cl + SO4 + 2H
+
217
ORGANIC PREPARATIONS
Procedure: Dissolve 30 g of cupric sulfate (CuSO4 . 5H 2O) in 100 ml of water in a 500 ml
round-bottomed flask by heating. Add 10 g sodium chloride (Note I) . In another Erlenmeyer
flask dissolve 7 g of sodium bisulfite in 75 ml of water. Add this solution (reducing solution) to the hot copper sulfate solution during 5 min. Shake well and cool the flask in ice. Step B: Diazotisation Procedure: Place 11 g of p-toluidine, 15 ml of water and 25 ml of conc. hydrochloric acid in a 250 ml Erlenmeyer flask and shake. Keep the flask in an ice-bath. The salt p-toluidine hydrochloride separates out. Dissolve 7 g sodium nitrite in 20 ml of water and add this solution dropwise to the amine salt keeping the temperature between 05oC. Occasionally add ice into the flask. After the addition is over, a clear solution of the soluble diazonium salt is obtained ( Note II).Keep the flask in ice. Step C: The Sandmeyer reaction Procedure: Decant the supernatant liquid from the colorless solid cuprous chloride prepared in ( Step A ) . Wash the white solid with cold water and then dissolve in 45 ml conc. hydrochloric acid. Pour the cold diazonium salt solution slowly in the ice-cold cuprous
chloride solution with constant shaking. The mixture initially becomes very thick (Note
III) . Allow the mixture to come to room temperature with occasional swirling. When the temperature reaches about 15o C, the complex starts decomposing with the evolution of nitrogen and an oil separates out. Warm the contents to 60oC on a water-bath to complete the decomposition. Steam distil the mixture until no more oil passes over. Transfer the distillate to a separatory funnel and remove the lower layer of p-chlorotoluene. Wash it
with 10% sodium hydroxide solution ( Note IV) and subsequently with water. Dry over anhyd. magnesium sulfate, filter and evaporate ether. Distil the residue and collect p-chlorotoluene passing over between 156160oC. The yield is 10.6 g. Notes I: On adding sodium chloride a small precipitate of basic copper chloride may be formed. II: At this stage a small excess of nitrous acid should be present. A blue color should be obtained with a starch iodide paper when touched with a drop of the solution. +
III: Due to the presence of a double salt of p-CH3C6 H4 N2 Cl . CuCl. IV: To remove any p-cresol present.
8.15.3 Preparation of o-Chlorobenzoic Acid (The Sandmeyer Reaction) The acid is obtained from anthranilic acid by the Sandmeyer reaction.
218
LABORATORY MANUAL OF ORGANIC CHEMISTRY
Procedure: In a 250 ml Erlenmeyer flask dissolve 5 g anthranilic acid in a mixture of 7 ml of conc. hydrochloric acid and 35 ml water. Cool the solution to 5o C. In another Erlenmeyer flask prepare a solution of 2.5 g of sodium nitrite in 10 ml water and cool to 5oC. Add this solution to the salt of anthranilic acid slowly and with stirring keeping the temperature at 5oC. After the addition is complete allow the diazotised solution to cool at 5oC. Dissolve 9.3 g of copper sulfate and 8.6 g of sodium chloride in 20 ml of water in a 500 round-bottomed flask. Heat the mixture to boiling, then add 30 ml conc. hydrochloric acid and 5 g of copper turnings and continue heating under reflux till the solution becomes colorless. Cool the cuprous chloride solution in ice and add the cold diazotised solution slowly with shaking. Allow the solution to stand in ice with frequent shaking for 1 hr. Filter the solid and wash with cold water. Recrystallize from hot water. The yield is 4.9 g, m.p. 139140oC.
8.16 PREPARATION OF DYES An important use of diazotisation is in the preparation of dyes. The diazonium compound is coupled with another aromatic nucleus containing an ortho or para directing group. Dyes find applications in industry and as indicators in the laboratory.
8.16.1 Preparation of Methyl Orange This azo dye is prepared by coupling diazotised sulfanilic acid with N, N-dimethylaniline in a weakly acidic solution. Anilines usually require acidic medium.
Procedure: Dissolve 4.8 g of sulfanilic acid in 50 ml of 2.5% sodium carbonate solution in an Erlenmeyer flask by boiling. Cool the solution to 15 o C and to this add 1.9 g sodium nitrite and stir. Pour it in a beaker containing 25 g of crushed ice and 5.0 ml conc. hydrochloric acid. Soon a white precipitate of the diazonium salt separates out. In a second Erlenmeyer flask mix 3.2 ml of dimethylaniline and 2 ml galcical acetic acid to dissolve amine as its salt. Add this solution to the cold suspension of diazotised sulfanilic acid with
ORGANIC PREPARATIONS
219
continuous stirring. Some coupling takes place in the acid medium and the dye imparts red color to the solution. Now add 35 ml of 10% sodium hydroxide solution to produce an orange colored sodium salt. Stir well with a glass rod and add 25 g sodium chloride. Heat the mixture to boiling, then cool in an ice-bath for some time. The dye separates out as orange crystals. Filter, wash with a little ethanol and dry. The yield is 56 g.
Question 8.26 In the preparation of methyl orange, why is sulfanilic acid converted into its sodium salt?
8.16.2 Preparation of Phenolphthalein Phenolphthalein is used as indicator in acid-base titrations. It is prepared by condensing phthalic anhydride with two molecules of phenol. It gives pink color in alkaline solution.
Procedure: Take 19 of phenol in a large tube to this add 0.79 of phthalic anhydride and mix well with a glass rod. Add about 1012 drops of conc. sulfuric acid and stir well with a thermometer. Heat the viscous mass for 45 min at approximately 160 oC. Pour the hot melt into 100 ml of water in a beaker. Filter the solid and wash with cold water. Weigh the dry sample.
220
LABORATORY MANUAL OF ORGANIC CHEMISTRY
8.16.3 Preparation of Fluorescein This dye is a condensation product of phthalic anhydride and two molecules of resorcinol in the presence of anhydrous zinc chloride catalyst.
Procedure: Grind 5 g phthalic anhydride and 7.4 g resorcinol in a mortar. Transfer the mixture to a 250 ml Erlenmeyer flask, immerse a thermometer and heat the flask slowly to
180oC on a sand-bath. In the meantime weigh 2.3 g of anhyd. zinc chloride (Note I) in a small stoppered bottle and add it to the reaction mixture in small lots by stirring with the thermometer after each addition. Continue heating the mixture till it becomes dark red
and highly viscous (Note II). Cool the flask to about 90o C and to this add 70 ml water and 3.5 ml conc. hydrochloric acid. Heat again till zinc salts have dissolved. Filter the colored salt on a Buchner funnel, wash with water, drain well and dry in an oven at 100 oC. The yield is 8.6 g. Notes I: If ZnCl2 appears moist, dry by fusing it in a procelain dish in an oven. II: This may take about 4050 min.
Question 8.27 Why is anhydrous zinc chloride needed in the preparation of fluorescein dye?
ORGANIC PREPARATIONS
221
8.16.4 Preparation of Eosin Eosin is a tetrabromo derivative of fluorescein. Its bromination in the presence of excess bromine leads to eosin.
Procedure: Take 5 g of the dried fluorescein in a 250 ml Erlenmeyer flask and add 25 ml of
ethanol and shake. Weigh 10.8 g of bromine (Note I) and transfer to a dropping funnel. Add bromine slowly to fluorescein solution with constant stirring. When about half of the bromine
has been added a solid appears (Note II). More tetrabromofluorescein precipitates out as the addition is continued. Allow the mixture to stand for 1 hr at room temperature. Filter the solid on a Buchner funnel, wash twice with ethanol and dry in an oven at 100 o C. The yield of the orange dye is 7.2 g. Notes I: Work with bromine is the fume hood. II: This is so because dibromofluorescein is soluble in ethanol.
Questions 8.28 Why do you not observe the evolution of HBr gas during bromination? 8.29 Why do these four places in fluorescein get brominated?
8.16.5 Preparation of Methyl Red This dye is obtained by coupling N, N-dimethylaniline with diazotised anthranilic acid. This dye is used as an indicator.
222
LABORATORY MANUAL OF ORGANIC CHEMISTRY
Procedure: Dissolve 6.5 g of crystallized anthranilic acid in a mixture of 5 ml of conc. hydrochloric acid and 15 ml of water. Filter the solution to remove any suspended particles. Pour the solution in a 250 ml beaker immersed in an ice-bath. To the beaker add 20 g of crushed ice and 8 ml of conc. hydrochloric acid and stir continuously with a glass rod. When the temperature of the solution reaches 23o C, add a cold solution of 3.5 g of sodium nitrite prepared separately in 10 ml water. (Note I). It is essential that during this addition the temperature remains below 5oC (Note II). To the resulting solution of the diazonium salt of anthranilic acid add 8.5 g (8.9 ml) of dimethylaniline slowly with vigorous stirring. After the addition is complete, continue stirring for an additional period of 15 min maintaining the temperature below 5o C (Note III). Keep the reaction mixture aside. Dissolve 6.8 of sodium acetate in 12 ml water and add 6 ml of this solution to the above reaction mixture with continuous cooling and stirring. Allow this mixture to stand overnight in an ice-box at a temperature of not above 7oC. Then add the remaining of the sodium acetate solution with stirring to the cooled mixture. Stir for one hour and again allow to stand for 24 hrs and during this period allow the temperature to rise above 25oC. To this reaction mixture add 2.5 ml of a 40% sodium hydroxide solution with stirring. Filter off the solid at the pump. Wash it with water followed by 10% acetic acid and finally with water. Dry the dye and then suspend it in 40 ml of methanol in a round-bottomed flask. Stir the mixture and reflux for 1 hr. Cool the flask in ice whereby methyl red dye precipitates out. Filter the solid and dry, yield is 7.5 g, m.p. 181182oC. Notes I: Check with a starch paper. II: Otherwise tarry products are formed. III: Add ice if necessary.
8.17 THE PINACOL-PINACOLONE REARRANGEMENT Pinacol (2, 3-dimethyl -2, 3-butanol ) when treated with conc. sulfuric acid rearranges to pinacolone (3, 3-dimethyl-2-butanone). Such a rearrangement is known as the Beckmann rearrangement and proceeds according to the following mechanism:
ORGANIC PREPARATIONS
223
The ketone has been used for the preparation of pivalic acid by oxidation with sodium hypobromite. The preparation is carried out in two steps: Step A: Preparation of pinacol Procedure: Reduction of acetone with most reducing agents yields isopropyl alcohol and a small quantity of pinacol as by-product. However, reduction in the presence of amalgamated magnesium yields a considerable amount of the bimolecular reduction product, pinacol.
Pinacol is isolated as its haxahydrate. Procedure: Fit a 500 ml dry two-necked flask ( Note I) with a reflux condenser, a dropping funnel and place 8 g of magnesium turnings and 100 ml dry benzene. Take a solution of 9 g of mercuric chloride in 75 ml dry acetone in the dropping funnel. Add about 20 ml solution to the flask. If the reaction does not start immediately warm the flask on a steam-bath. Cool the flask in an ice-bath in case the reaction becomes too vigorous. Add the remaining solution from the dropping funnel slowly. After the addition is complete, heat the flask on a steam-bath for 1 hr with occasional shaking. If the formation of solid magnesium pinacolate makes stirring difficult, break the lumps with a glass rod. At the end of 1 hr pour 20 ml of water through the condenser and boil the mixture for 30 min with frequent stirring. This brings about hydrolysis of magnesium pinacolate to magnessium hydroxide and pinacol dissolves in benzene-acetone mixture. Filter the hot solution and return the precipitate of magnessium hydroxide to the flask and reflux again for 1520 min after adding 50 ml of ordinary benzene. Filter the solution again. The combined benzene solution is evaporated in a beaker on a steam-bath to 1/3 of its volume. Then add 15 ml water and cool well in an ice-bath. Pinacol hydrate separates as an oil which immediately solidifies. Filter on a Buchner
funnel, wash with cold benzene and drain. Recrystallize the solid from hot water (Note II) . The yield is 1820 g, m.p. 4647 oC. Notes I: A three-necked flask may instead be used. II: Pinacol hydrate is highly soluble in hot water. If the solution is too dilute to permit crystallization, evaporate some water.
Step B: Preparation of pinacolone
Pinacol rearranges to pinacolone (3, 3-dimethyl-2-butanone ) in the presence of an acid as catalyst.
224
LABORATORY MANUAL OF ORGANIC CHEMISTRY
Procedure: Dissolve 15 g of pinacol hydrate in a solution of 60 ml water and 15 ml conc. sulfuric acid in a 200 ml round-bottomed flask equipped with a reflux condenser. Add a few boiling chips replace the condenser and reflux gently for 15 min. An oily upper layer of pinacol begins to form as boiling progresses. Cool the flask and add 25 ml water and set up for distillation. Distil pinacolone which passes over along with some water. Transfer the distillate to a separatory funnel and separate pinacolone from water. Dry over anhyd. calcium chloride. Purify the product by distillation, using a fractionating column. The yield is 15.0 g, b.p. 106oC.
Some 2, 3-dimethyl-1,3-butadiene (b.p. 70oC) also distils over. To remove it, heat the flask slowly in the beginning and discard 12 ml of the forerun.
Questions 8.30 Explain the mechanism for the fromation of 2-3-dimethyl-1, 3-butadiene in the preparation of pinacolone. 8.31 From which glycol can the following compound be synthesized by a pinacol-pinacolone rearrangement? Write the mechanism.
8.18 CHROMATOGRAPHIC METHODS A widely used technique for the separation of a desired compound from its impurities or a mixture of compounds into its components is chromatography. The name to this technique was given by the Russian chemist, Tswett at the turn of the century. He used it for the separation of colored compounds (chroma, color). Analogous to extraction, chromatography also depends on the principle of phase distribution. In this technique the components of a mixture are selectively adsorbed on a stationary phase and are then dislodged from it by a mobile phase. Various types of chromatographic methods are classified according to the physical states of the different phases involved, i.e., stationary and mobile. The mobile phase can be gas or liquid, while the stationary phase can be solid or liquid. When the separation involves
partitioning between two liquid phases (one of them absorbed on the solid phase) then it is referred to as partition chromatography or liquid-liquid chromatography. Those in which solid-liquid interaction takes place are classified as column Chromatography, high
ORGANIC PREPARATIONS
225
pressure liquid chromatography and ion exchange. In gas liquid chromatography
(glc ), on the other hand, the mobile phase is a gas while the stationary phase is a liquid
coated on a solid. Gel chromatography or gel filtration is a case of an exclusion chromatography in which the solid phase is a gel and separation takes place on the basis of molecular size.
8.18.1 Column Chromatography In this type of chromatography the separation is affected by adsorption on a solid stationary phase. Several types of forces that cause interactions of the substance with the solid are hydrogen-bonding, van der Waals forces, electrostatic interactions. A cylindrical glass column of the type shown below is employed to separate a mixture by column chromatography. To pack a column, first clean it thoroughly and dry. Now position it vertically on an iron-stand with the help of a clamp. Close the stopcock and fill the column with an appropriate solvent. Insert a small plug of glass wool to the bottom of the column. Pour some dry sand so that it forms a 1 cm layer on the top of the glass wool. Add slowly the adsorbent i.e., alumina or a
slurry (if it is silica) on the top of the column with constant tapping the sides of the column. An adsorbent is a porous solid that can retain both solute and solvents. Open the stopcock and allow the solvent to drain out simultaneously at a rate of 12 drops per sec. When all the adsorbent has been added, introduce more sand to form a 1 cm layer at the top of the packing. The column is now ready for use. The adsorbents of common choice are alumina, silica gel, cellulose, charcoal, etc. Several considerations govern the choice of an adsorbent. It should be insoluble in the solvent and must not react with the substance to be separated. The mixture to be separated is then taken in a minimum amount of solvent and introduced
from the top of the column. Then a suitable solvent (mobile phase) is allowed to percolate through the column. The process is known as elution. It is customary to use a relatively non-polar solvent in the beginning. The adsorption depends on both the nature of the solvent and the adsorbent. For effective separation the eluting solvent must be significantly less polar than the components of the mixture. In case the solvent is more polar and strongly adsorbed than the components of the mixture will remain in the mobile phase and little if any, separation will take place. It is also essential that the mixture is soluble in the solvent, otherwise it will remain permanently adsorbed on the adsorbent. Polar solvents are used for eluting strongly adsorbed components while non-polar solvents are used for weakly adsorbed components of a mixture. An approximate order of increasing polarity of some common solvents is as follows: petroleum ether, hexane, carbon tetrachloride, toluene, chloroform, and water. A mixture of two solvents may be more useful for separation in many instances.
226
LABORATORY MANUAL OF ORGANIC CHEMISTRY
Fig. 8.2 A packed adsorption column.
(a) Separation of anthracene from anthracene picrate Anthracene picrate is prepared from anthracene and picric acid. It is a loosely bound compound of the two reagents. The forces holidng them together are weak. When solution of the complex is added on the column picric acid is strongly adsorbed white anthracene is adsorbed only weakly. This as a result, passes rapidly through the column. Technical grade anthracene is often colored and this serves a method for its purification. Procedure: Fix an appropriate cleaned glass column on an iron-stand vertically. Pack the column with 50 g of alumina in the manner described earlier using benzene as solvent. Separate anthracene picrate and dry it. Apply 1 g of this sample dissolved in minimum quantity of benzene to the column with the help of a pipette. Open the stopcock to permit the solvent to flow out. The solute will be adsorbed on the adsorbent. Wash the side of the column with about 2 ml of benzene, and also allow it to run down (Note I) . Add 100150 ml
of benzene and elute anthracene ( Note II) . When all the anthracene has been washed down, wash the column with 50100 ml of ethanol to elute picric acid and collect the elutant in a separate flask. Evaporate first fraction under reduced pressure to obtain anthracene as colorless, highly fluorescent plates of m.p. 216o C. Record the weight of anthracane and determine the total recovery.
227
ORGANIC PREPARATIONS
Notes I: Do not allow the column to get dry, it will develop cracks. II: The completion of elution can be periodically checked by exposing the column to u.v. light. Anthracene shows a strong fluorescene.
8.18.2 Thin Layer Chromatography (TLC) Thin layer chromatography involves the same principle as column chromatography. It is a form of solid-liquid adsorption chromatography in which the stationary phase is spread on a glass plate. Izmailov and Shraiber in 1938 developed this technique. However, it was due
to the efforts of Stahl (1958) that this technique was ultimately accepted as a new modern technique of analytical chemistry. This method is simple, rapid in separation and very efficient. Some sepcial grades of adsorbents are used in TLC. There are different ways of coating the glass plates with an adsorbent such as pouring, dipping, spraying. The solid
adsorbent is spread in a thin layer ( 0.25 mm thickness) on a glass plate with the help of a spreader. The same solid adsorbents used in column chromatography can be used here, however, silica and alumina are most common. It is also more fine and is mixed with a small amount of binder, for instance, plaster of paris or calcium sulfate, so that the adsorbent does not flake off on drying the plate. The sample is applied as a solution in a non-polar solvent at one end of the plate in the form of a symmetrical spot (use a syringe or
a capillary tube) and the spots dried. It is often necessary to repeat this process to get several milligrams of the sample on the plate. Therefore use 23 successive applications for each spot. The plate is then dried and placed in a chamber saturated with the solvent. Solvent for development is selected on the basis of the nature of the components. Do not move or disturb the chamber during development. The various components are then separated depending on the preferential adsorption on the plate. After the solvent has moved a distance of approximately 10 cm on the plate, the plate is taken out and dried. The detection of spots on the chromatogram can be visualized by a number of reagents. For instance, sulfuric acid, potassium permanganate solution, p-anisaldehyde etc. can be sprayed on the plate and the spots are revealed as colored compounds. Iodine is another reagent which is widely used. In this the dried plate is placed in a closed container containing some iodine crystals. The iodine vapors are adsorbed into the areas of the plate containing organic compounds and brown sports appear due to the formation of iodine charge-transfer complexes. Sometime exposure of the plate to u.v. light permits location of the spots for compounds that fluoresce.
Under a given set of conditions (adsorbent, solvent, plate thickness, etc.) TLC technique can be used for identification purpose also. For this purpose RF value which is the ratio of the distance travelled by the substance from the origin to the distance travelled by the solvent from the origin is measured.
RF =
Distance travelled by the substance front Distance travelled by the solvent front
The application of this technique is demonstrated by the following two experiments:
228
LABORATORY MANUAL OF ORGANIC CHEMISTRY
(a) Separation of green leaf pigments Green leaves often contain chlorophylls, carotenoids and xanthophylls. On separation they appear as colored spots. Procedure: In a mortar place 15 ml of a mixture of petroleum ether and ethanol (2 : 1) and a few green leaves ( Note I) . Crush the leaves with a pestle. Transfer the extract with a pipette to a separatory funnel. Swirl (Note II) the extract with an equal volume of water. Discard the lower aqueous layer. Repeat the washing twice with 5 ml portions of water. Washing with water serves to remove ethanol and other water soluble material. Transfer the extract to a small Erlenmeyer flask and dry over 2 g of anhyd. sodium sulfate. Filter and concentrate the solution if necessary by a stream of dry nitrogen. Place a small spot with the help of a capillary tube on a 10 cm TLC plate. The spots must be above the level of the solvent. Allow the spot to dry and develop the chromatogram using chloroform as a
developing solvent. A wide-mouthed bottle (Fig. 8.3) can be used in place of a chamber. A folded piece of filter paper may be placed into the bottle to maintain a saturated atmosphere in the bottle.
Fig. 8.3 Arrangement for developing a TLC plate.
Dry the plate again, and it will be possible to observe as many as eight colored spots. Determine the RF values. In the order of decreasing RF values, the spots may be identified
as carotenes (2 spot, orange ), chlorophyll a (1 spot, blue and green), chlorophyll b (1 spot, green) and xanthophylls (4 spots, yellow).
Notes I: Green leaves or spinach may be used. II: Shaking may lead to emulsion formation.
(b) Separation of 2, 4-dinitrophenylhydrazones The 2, 4-dinitrophenylhydrazone derivative of aldehydes and ketones are colored and can be separated and easily visualized on TLC plates. Procedure: Prepare 2, 4-dinitrophenylhydrazones of acetone, benzaldehyde and acetophenone according to the procedure given earlier. Coat a 10 cm plate using silica gel.
ORGANIC PREPARATIONS
229
Prepare a solution in chloroform or dioxane by mixing 10 mg of each hydrazone. Spot the TLC plate with this mixture solution as well as apply one spot each of the individual pure hydrazone for comparison. Allow the spots to dry and then place the plate in a developing
chamber containing benzene: Petroleum ether (3 : 1 ) solvent. Develop the chromatogram. Remove the plate from the chamber, mark the position of the solvent front and the colored spots. Allow the plate to dry. Estimate the RF values and identify the separation of the mixture with the help of the standard spots.
8.18.3 Paper Chromatography Paper chromatography is similar to thin layer chromatography. In this technique a small spot of the sample is placed near one end of a strip of filter paper. The paper strip is suspended in a jar in such a way that the end of the paper strip is immersed in the developing solvent. The sample is separated into individual spots as the solvent ascends the paper. In this case a distribution takes place between water (adsorbed by the filter paper to an extent
of 20%) and the mobile solvent. It is for this reason it is also referred to as liquid-liquid partition chromatography. The different compounds may be identified by calculating the R F values. Paper chromatography is useful for polar molecules like amino acids. The individual spots of amino acids are visualized by spraying with ninhydrin solution (0.1% solution in
95% ethanol ) and a blue-violet color is produced. The color forming reaction takes place as follows:
230
LABORATORY MANUAL OF ORGANIC CHEMISTRY
Most of the amino acids give blue color (except proline which gives a yellow color) it indicates that the colored product formed is the same in this reaction.
(a) Separation of a mixture of =-amino acids Paper chromatography is a valuable tool for the separation of a-amino acids as they migrate at different rates. Procedure: From Whatmann No 1 filter paper, cut a strip measuring 30 × 10 cm. Draw a line with a pencil about 3 cm from one edge. Prepare amino acid solutions by dissolving 120 mg each of glycine, proline, phenylalanine, leucine and aspartic acid in 20 ml of water. Spot the paper with the mixture of the above amino acids and also put one spot each of the individual acid about 1.5 cm apart. The spot should be 23 mm in diameter. If it is too large it may lead to poor resolution during development. Allow the spots to dry. Fasten the paper with clips and insert it into a glass cylinder containing the developing solvent (n-butanol :
glacial acetic acid : water respectively in a ratio of 4 : 1 : 5). Make sure the paper does not touch the sides of the cylinder and the samples spots are above the level of the solvent. The solvent will rise by capillary action. When the solvent front has migrated two thirds the length of the paper, remove the paper and mark the position of the solvent front. Dry the chromatogram. Now spray it lightly but evenly with ninhydrin solution and dry it again. Heat the chromatogram in an oven at 105oC for 15 min, whereby the colors are visible. Mark the positions of the spots with a pencil and estimate the RF values.
Questions 8.32 What factors govern the choice of a solvent in column chromatography? 8.33 Why do iodine vapors yield colored spots on TLC? 8.34 Why should the initial spots of amino acids must not be too large?
8.19 POLYMERIZATION A polymer may be described as a large molecule formed by linking together a number of smaller molecules. These smaller molecules have low molecular weights and are joined by covalent bonds. The smaller unit is called a monomer. Monomer
(Monomer)n (A polymer)
Those polymers in which the two monomers are bonded end-to-end in a linear manner usually dissolve, become soft when heated and can be moulded are referred to as thermoplastic. On the other hand, if the polymer chains are linked together at several points, the polymer is one large three-dimensional net-work, insoluble and infusible, and
ORGANIC PREPARATIONS
231
cannot be moulded, such polymers are called thermosetting. These polymers are crosedlinked polymers. The process of making high molecular weight compounds is said to be polymerization. Such a process can be initiated by an ionic or radical reaction. Two types of polymers are recognized: (a) addition (b) condensation polymers. Polymers, nowadays, are not difficult to prepare because of the easy availability of the raw material. The synthetic polymers are made from smaller molecules by chemical means. They are also referred to as man-made polymers.
8.19.1 Preparation of Phenol-Formaldehyde Resin The polymers used in industry are also sometime referred to as resins. Formaldehyde condenses readily with phenol in the presence of a catalyst at the o- and p-positions. The resin so obtained is called Novolac having a molecular weight between 1200 and 1500.
Procedure: In a 250 ml round-bottomed flask fitted with a reflux condenser place 65 g of
phenol, 46 g of 37% aq. formaldehyde solution (formalin) and 0.5 g oxalic acid. Reflux for an additional period of 1 hr. The mixture becomes viscous. Add 150 ml of water and cool the flask in ice. Allow the mixture to stand for some time then decant off the supernatant liquid. The resin is obtained as a pasty mass. The yield is 65 g. Water can be removed from the resin at the pump till it becomes a brittle solid.
8.19.2 Preparation of Thiokol Rubber A group of synthetic rubbers are known which do not exactly approximate natural rubber. These substances are called thiokols. These rubbers are prepared from a dihalo organic compound and sodium polysulfide (usually Na2S4).
Procedure: In a 100 ml beaker dissolve 2 g sodium hydroxide in 5060 ml of warm water. Boil the solution and to this add in small lots with constant stirring 4 g of powdered sulfur
(Note I). During addition and stirring the yellow solution turns dark brown. After 5 minutes, allow the solution to cool and decant the dark brown liquid from the undissolved sulfur.
Add 10 ml of 1, 2-dichloroethane (ethylene chloride ) with stirring. Warm the mixture to 6070oC and stir for an additional period of 20 min while rubber polymer separates out as a
232
LABORATORY MANUAL OF ORGANIC CHEMISTRY
lump at the bottom. Pour out the liquid from the beaker in the sink and collect the thiokol rubber. Wash it thoroughly with water under the tap. Dry in the folds of filter papers. The yield is about 1.5 g. Determine the solubility of the polymer in benzene, acetone, 5% sulfuric acid and nitric acid. Note I: If some sulfur remains undissolved filter the solution.
8.19.3 Polymerization of Styrene Polymerization of styrene to polystyrene is an example of addition polymerization. Polystyrene is prepared by a free radical polymerization using benzoyl peroxide as a radical initiator. Trade name for polystyrene is thermocole.
Procedure: In a 100 ml separatory funnel pour 15 ml of commercial styrene and shake with 25 ml of water and 5 ml of 10% sodium hydroxide solution. Discard the aqueous layer and wash the styrene layer thrice with 10 ml portions of water. Dry it over anhyd. calcium chloride in a small Erlenmeyer flask. This process removes the antioxidant usually 2, 6-di tert-butylphenol added to stabilize styrene. Decant styrene from the Erlenmeyer flask into a boiling tube, add 0.3 g benzoyl peroxide and 25 ml toluene. Allow the tube to stand in a beaker of boiling water maintained at 9095oC. Remove the test tube after 1 hr and allow it to cool to room temperature. Pour the solution into 200 ml of methyl alcohol contained in a beaker. Filter the white precipitate of polystyrene on a Buchner funnel and wash with 50 ml of methyl alcohol and dry in air. Determine the solubility of polystrene in benzene, ethyl alcohol, carbon tetrachloride and water.
Question 8.35 How does sodium hydroxide remove the antioxidant from styrene?
ORGANIC PREPARATIONS
233
8.19.4 Preparation of Nylon-66 Nylon-66 is a typical condensation polymer. It is prepared by condensing hexamethylenediamine with adipic acid in the presence of sodium hydroxide.
In the laboratory this polymer is prepared between adipoyl chloride dissolved in a water immiscible organic solvent and a water solution of the diamine. The reaction occurs at the interface of the two solutions and is thus called interfacial polymerization. Procedure: Place a solution of 2 ml of adipoyl chloride in 100 ml hexane in a 200 ml beaker. Make a solution of 2 g hexamethylenediamine and 1.5 g sodium hydroxide in 50 ml water in another beaker. Pour this solution on the adipoyl chloride solution carefully. A polymeric film starts forming immediately at the interface of the two liquids. Remove the polymeric film with a forceps and raise it from the beaker as a continuously forming a rope. Wash the polymer with water thoroughly. Finally wash it with 50% aqueous acetone and allow it to dry in air. Place a small amount of the dried film on a watch glass and melt it carefully on a hot plate so that it does not get charred. Pull the molten polymer with a glass rod to draw it into a fibre.
Question 8.36 Describe interfacial polymerization.
8.20 CATALYTIC HYDROGENATION Catalytic hydrogenation is an important reaction both in the research laboratory and industry. The performance of such an experimet, however, requires the use of special apparatus and potentially hazardous hydrogen gas. A safe and alternative procedure will be described here for the catelytic hydrogenation of cinnamic acid.
8.20.1 Conversion of Cinnamic Acid to Hydrocinnamic Acid Method A: For this reaction palladium on activated carbon is used in tetralin. The latter reagent functions both as a solvent and as a source of hydrogen.
234
LABORATORY MANUAL OF ORGANIC CHEMISTRY
Tetralin is smoothly dehydrogenated to naphthalene and hydrogen is released. The reaction takes place under refluxing conditions and at atmospheric pressure. Procedure: Place 5 g of cinnamic acid in 25 ml tetralin in a 100 ml round-bottomed flask. To this add 0.1 g of 30% palladium on activated carbon. Fit the flask with an air-condenser and reflux the mixture for 1.5 hr. Cool and dilute with 25 ml ether. Filter the palladium catalyst and extract the filtrate with two 10 ml portions of 10% sodium hydroxide solution. The hydrocinnamic acid dissolves in the aqueous layer, save the organic layer for the
isolation of naphthalene (Note I). Acidify the alkaline extract with conc. hydrochloric acid until it is acidic to Congo red paper. Cool and extract again with two 30 ml portions of ether. Dry the ether solution over anhydrous calcium chloride. Distil off ether on a steambath and allow the residue to crystallize. Recrystallize the acid from hot ethanol. The yield is 22.5 g, m.p. 48.5oC. Note I: Naphthalene may be obtained from the organic layer by making its picrate with picric acid.
Method B: The second method consists of the reduction of cinnamic acid by diimide generated in situ by the copper catalyzed oxidation of hydrazine in the presence of an oxidizing agent (H2O2).
ORGANIC PREPARATIONS
235
The reduction of C = C bond with diimide involves a stereospecific addition of hydrogen via a non-polar cyclic transition state. Though in the above reaction both cis and transforms of diimide are formed but the former form is involved in reduction. Procedure: Dissolve 2 g of cinnamic acid in 2.5 g hydrazine (or 4.0 g of hydrazine
hydrate) in a 500 ml beaker. To the clear solution add 25 ml of water and shake (Note I). Immerse the beaker in an ice-bath and to it add with stirring a few crystals of cupric sulfate. To the cooled solution add 10 g hydrogen peroxide (30%) slowly such that the
temperature remains below 30oC as an exothermic reaction commences (Note II). After the addition is complete allow the beaker to stand in the ice-bath for 30 min followed by 10 min at room temperature. Again cool the beaker and add a few ml of 1 : 1 conc. hydrochloric acid with stirring. Hydrocinnamic acid separates out frequently as an oil. Cool to crystallize the oil. Recrystallize from wet ether, yield 0.8 g, m.p. 48.5o C. Notes I: Add water only after cinnamic acid has dissolved in hydrazine hydrate. II: Add cooled hydrogen peroxide dropwise otherwise tarry products would be obtained.
Question 8.37 Name other reducing agents which add in a syn manner to alkenes.
8.21 PHOTOCHEMICAL REACTIONS A thermal reaction is promoted by heat whereas a photochemical reaction derives its energy from the absorption of light radiation. For a photochemical reaction to take place, the substance must absorb energy in the wavelength region in which it is irradiated. This can be determined by the absorption spectrum of the compound. Photochemical reactions have proven invaluable in organic syntheses.
8.21.1 Preparation of Benzopinacol Photochemical preparation of benzopinacol from benzophenone is one of the oldest methods. The reaction can be initiated by sunlight.
Procedure: Place 10 g of benzophenone in a 100 ml round-bottomed flask and dissolve in 6070 ml of isopropyl alcohol by warming. Fill the flask to the neck with more alcohol and
236
LABORATORY MANUAL OF ORGANIC CHEMISTRY
add one drop of glacial acetic acid ( Note I). Stopper the flask tightly which is wired in place. Invert the flask in a 100 ml beaker and expose it to direct bright sunlight. The formation of benzopinacol can be followed by the appearance of colorless crystals around the walls of the flask, as it is only sparingly soluble in alcohol. After 45 hrs some crystals separate out, and 95% of the reaction is complete in about four days (Note II). Chill the flask and filter the crystals on a Buchner funnel. Wash the solid with a small amount of cold ethanol.The product is generally pure, m.p. 188189o C. Notes I: A drop of glacial acetic acid must be added, otherwise enough alkali may be derived from the flask to cleave the diol to benzhydrol and benzophenone. II: If any benzophenone crystallizes out it must be dissolved in alcohol by warming.
8.21.2 Photochemical Isomerization of Azobenzene The isomerization of azobenzene can be accomplished photochemically. The cis-azobenzene is thermodynamically unstable and the position of equilibrium depends on the wavelength
of the incident light. Using a radiation of l = 365 mm, predominantly (90%) cis-compound is obtained. Sunlight can also be used as a source of radiation for this isomerization.
Procedure: Dissolve 0.5 g commercial azobenzene in 500 ml benzene and store the solution
in a stoppered brown bottle. Take two thin-layer chromatography (TLC ) plates and spot each of these plates, using an ordinary capillary tube about 1 cm from the bottom of the plate. Place one plate in the locker where it can be protected from light but expose the other to sunlight for 1 hr. Then develop both the plates in a chamber containing 3 : 1
cyclohaxane-benzene (v/v) to a depth of about 0.5 cm. Remove the plates after the solvent front has travelled to within 1 cm of the top of the silica layer on the plates. Two spots of yellow compound would be visible on each plate. The spot near the starting point is that of the more polar cis-azobenzene while the spot with a larger RF value is due to the non-polar trans-isomer. Measure the relative areas of the two spots on each plate. It may be noticed that depending on the previous history of azobenzene, the cis-compound may be obtained on the irradiated plate.
237
ORGANIC PREPARATIONS
8.22 THE HALOFORM REACTION
When methyl ketones
react with halogens (X2) in aqueous sodium hydroxide
solution they are cleaved to yield a carboxylic acid and haloform (CHX3 ). Accordingly, iodoform is obtained using iodine halogen and a methyl ketone.
8.22.1 Preparation of Iodoform Procedure: Place 3 ml of acetone, 30 ml water and 15 ml of sodium hydroxide ( 10%) solution in an Erlenmeyer flask. To the mixture add iodine solution (12.5 g of iodine dissolved
in a solution of 25 g of potassium iodide in 100 ml of water) dropwise with constant shaking till the color of iodine persists. Heat the contents on a water-bath at 60oC. Add more iodine if the color disappears. Heat till yellow precipitates settle down. Cool, filter and recrystallize from aqueous methanol, the yield is 5 g, m.p. 199oC.
8.23 ISOLATION EXPERIMENTS Methods of isolation are simple enough to be easily adaptable and they do not involve any complicated reactions. The interest in the isolation of compounds from natural sources exists because of their many practical applications. It is also noteworthy that natural products present some of the greatest challenges to modern organic chemists.
8.23.1 Isolation of Caffeine from Tea Caffeine (1, 3, 7-trimethylxanthine) is an alkaloid present in coffee beans, tea leaves, energy drinks and diet cola.
238
LABORATORY MANUAL OF ORGANIC CHEMISTRY
Procedure: Boil on a Bunsen burner 20 g of tea leaves in a 500 ml beaker with 250 ml of distilled water for 25 min. Filter through a Buchner funnel without using the filter paper at the pump to remove the spent tea leaves. To the clear filtrate add, while stirring 60 ml of
10% lead acetate solution to precipitate tannins (naturally occurring polyphenols ). Leave the mixture undisturbed for 23 days. After this period filter it through a glass wool plug and concentrate the filtrate on a sand-bath to about 30 ml. Cool the residual solution and extract it thrice with 25 ml protions of chloroform ( Note I). Combine the chlorform extracts and remove most of the chloroform by simple distillation. Cool the residue and add 40 ml of petroleum ether and stir the mixture for 5 min. The yellow color of the organic extract can be decolorized by shaking with 2 ml of 10% sodium hydroxide solution followed by washing with the same volume of water. Dry the washed extract and remove the solvent under vacuum. Recrystallize the crude caffeine from minimum ( < 1 ml) quantity of boiling water. Determine the yield ad the melting point of the product, m.p. 235237o C.
Test for Caffeine Warm a few milligrams of caffeine with K4[Fe(CN )6] and HNO 3, a Prussian blue color is obtained. Note I: In case an emulsion forms, pass through a filter paper to facilitate the separation of two layers.
Question 8.38 State two sources of caffeine and its color test.
8.23.2 Isolation of Lycopene from Tomatoes Lycopene is a red pigment which is extracted from tomatoes and has the following structure:
In this exercise you will learn to isolate a product from natural source and purify it using column chromatography. Procedure: Weigh about 10 g of red tomato paste (ripe tomatoes can be mashed to prepare a paste ) into a 250 ml round-bottomed flask. Add 25 ml of methanol and 30 ml of
ORGANIC PREPARATIONS
239
dichloromethane. Heat the mixture under reflux for 5 min on a steam-bath with frequent shaking. Filter the mixture under suction and transfer the filtrate to a separatory funnel. Wash this mixture containing lycopene with three portions of 150 ml each with sodium chloride solution. Dry the organic larger over anhydrous magnesium sulfate. Filter and evaporate most of the solvent in vacuum without heating. To separate lycopene from the crude pigment extract, pack the chromatographic column with about 40 g of TLC grade silica gel using hexane. Dissolve the crude red pigment is 5 ml of light petroleum and transfer on the top of the column with a pipette. Elute it with hexane till a yellow band appears. At this stage, change the eluent to 10% acetone in hexane. An orange-red color band will start to appear. Collect a sample of the eluate from the center of this band. Evaporate to dryness under vacuum. Determine the approximate yield of lycopene.
8.23.3 Isolation of Casein from Milk Casein is the phosphoprotein present in milk and contains at least 15 amino acids. It is an amorphous and hygroscopic white solid insoluble in organic solvents. It is present to the extent of 3% in cow milk. The pH of fresh milk is approximately 6.6 and when it is acidified to pH 4.5 casein precipitates. Casein is the chief protein of milk and is the basis of curds and cheese. Procedure: Dilute 140 ml of cow milk with 500 ml water in a 1000 ml beaker and warm to 40o C. Then add dropwise with constant stirring 10% acetic acid to obtain all the casein precipitates. Allow to stand the beaker undisturbed for 5 min. Filter the precipitate on a Buchner funnel and wash successively thrice with 5 ml portions of water, 20 ml of ethanol and 10 ml of ether to remove all the fats. Dry the wet solid in a vacuum desiccator and weigh the dry powder. Test the solubility of casein in water, benzene, 5% hydrochloric acid and 5% sodium hydroxide solution.
8.23.4 Isolation of Piperine from Pepper Piperine is an alkaloid found in black pepper to the extent of 10% by weight and is known to be an amide. It possesses the following structure:
The other constituents of pepper being volatile oils (1.3%), starches (2040%) and water (813%). Piperine can be isolated by extraction of ground pepper with 95% ethanol. In an ideal case the extraction should be carried out in a Soxhlet apparatus as shown in Fig. 8.4. This method requires only a small amount of the organic solvent.
240
LABORATORY MANUAL OF ORGANIC CHEMISTRY
Fig. 8.4 Soxhlet extractor for the extraction of solids.
Procedure: In a 500 ml round-bottomed flask fitted with a reflux condenser add about 350 ml of 95% ethanol. Pack the thimble with 30 g of powdered pepper and place it in the apparatus as shown. The flask is heated for 3 hrs. Material is extracted out of the solid into the hot solvent. Filter the ethanol solution and concentrate the filtrate to 25 ml by distillation. To this residue add 30 ml of warm 2 N ethanolic potassium hydroxide solution. Stir the warm mixture and filter to remove any insoluble material. Warm the solution on a steambath and add 1520 ml of water. At this stage turbidity appears and yellow needles may separate. Keep this solution till the next laboratory period and filter the crude piperine. Recrystallize from acetone to obtain fine yellow needles, m.p. 129131oC.
Question 8.39 Is the piperine isolated expected to be optically active?
8.23.5 Isolation and Estimation of Aspirin Aspirin is acetylsalicyclic acid. It is both an ester and a carboxylic acid. The acid was first synthesized in 1853 and was introduced by Baeyer in 1899 under the trade name aspirin. It soon became the worlds most popular drug. Aspirin is known to lower fever, releive pain and reduce inflammation. The specific function of aspirin in the body was reported in 1971. It was proposed that aspirin inhibits the overproduction of prostaglandins in the body. Prostaglandins are hormonelike compounds that regulate body functions. An oversupply
241
ORGANIC PREPARATIONS
of certain prostaglandins can promote the formation of blood clots that lead to heart attack and strokes while others cause pain, fever and inflammation. Thus, there is a posibility that aspirin reduces these problems by blocking the overproduction of prostaglandins in the body. Aspirin also brings about a reduction of swelling in the joints and leads to relief of pain in people suffering from arthritis.
Isolation Procedure: An aspirin tablet contains aspirin and a starch binder. Powder an aspirin tablet on a filter paper and transfer it to a 25 ml. Erlenmeyer flask. To this add 10 ml of absolute alcohol and boil the mixture on a steam-bath. Aspirin will dissolve. Filter the hot solution and again heat to dryness. Recrystallize the residue from benzene, m.p. 130135 oC.
Estimation The amount of aspirin in a commercial table is determined by titration of its solution in alcohol against standard sodium hydroxide solution. Procedure: Weigh an aspirin table accurately. Powder it on a filter paper and dissolve it in 10 ml of absolute alcohol by boiling. Filter the hot solution in a 150 ml Erlenmeyer flask. Wash the insoluble residue on the filter paper with 3 additional 5 ml portions of hot ethanol. Make sure all the washings are done carefully. Add 20 ml of distilled water and 3 drops of phenolphthalein to the combined filtrates. Titrate the solution against 0.1 M sodium hydroxide solution to a faint pink color end-point. Note the volume of alkali consumed, the total volume of solution is 25 ml. Calculate the amount of aspirin by using the equation:
N × V = N 1 × V1
8.24 PREPARATION OF TRIPTYCENE Triptycene is prepared by the familiar Diels-Alder reaction between anthracene and a highly reactive dienophile namely benzyne. For this purpose benzyne is generated from anthranilic acid.
242
LABORATORY MANUAL OF ORGANIC CHEMISTRY
In this preparation, anthranilic acid is diazotised in the presence of isoamyl alcohol. Benzenediazonium-2-carboxylate is formed. It suffers decomposition to yield benzyne which is trapped by anthracene to form triptycene. Procedure: In a two-necked round-bottomed flask equipped with a reflux condenser and a dropping funnel, place 4 g anthracene and 4 ml isoamyl nitrile in 40 ml 1, 2dimethyoxyethane. Now take a solution of 10.4 g of anthranilic acid in 40 ml of 1, 2dimethyoxyethane in the dropping funnel. Heat the flask gently and pour half of the solution dropwise over a period of 2030 min to the flask. Remove the burner and add 4 ml isoamyl nitrite through the condenser. Again heat and run in the remaining anthranilic acid solution dropwise within a period of 30 min. After the addition of anthranilic acid is complete, reflux the mixture for 15 min. Cool and add into it 20 ml of ethanol and 6 g of sodium hydroxide solution in 80 ml water. Cool the mixture thoroughly in ice. Filter and wash the residue with ice cold aqueous methanol ( 4 : 1) and dry, yield 4 g. This product is contaminated with anthracene. This impurity can be removed by making its Diels-Alder adduct with maleic anhydride. Take this crude solid in a 250 ml round-bottomed flask fitted with an air condenser. To
it add 2 g maleic anhydride and 40 ml of triethylene glycol dimethyl ether (triglyme, b.p.
222oC). Reflux the mixture for 510 min. Then cool to 100oC and to it add 20 ml of ethanol and 1 g sodium hydroxide in 80 ml water. Cool in ice and filter. Wash the residue with aqueous methanol (4 : 1) and dry. Yield of triptycene is 3 g, m.p. 254oC.
Question 8.40 Would you expect the triptycyl anion to be stable?
8.25 ADDITION OF DICHLOROCARBENE TO CYCLOHEXENE Carbenes are neutral divalent carbon compounds. The central carbon atom has six electrons and is electron deficient. They act as reactive intermediates. They have only transient existence and are trapped by alkene derivatives. This type of reaction is of great synthetic utiltiy in the preparation of cyclopropanes. Cyclohexene, for instance, reacts with dichlorocarbene which is generated by treating chloroform with a strong base like potassium t-butoxide, to give 7, 7-dichloro [4.1.0] heptane.
Procedure: Place 20 ml of t-butyl alcohol in an Erlenmeyer flask and to it add 7 g of
potassium metal (Note I) in small portions with stirring. After all the potassium has reacted, cool the flask. To the cold potassium t-butoxide add 16 ml of dry cyclohexene followed by the addition of 3.2 ml chloroform dropwise with constant shaking. After the addition of
ORGANIC PREPARATIONS
243
chloroform is complete, continue shaking for 30 min. Pour the reaction mixture into a separatory funnel containing 25 ml water. Shake and collect the aqueous layer in a beaker.
Extract the aqueous layer thrice with 25 ml portions of petroleum ether (b.p. 4050oC) . Combine the extracts and dry this solution over anhydrous sodium sulfate. Filter and evaporate the solvent on a hot plate. Distil the residue at reduced pressure to obtain the pure product. The product is obtained as a colorless liquid. Determine its yield. Note I: Remove the oily layer on the potassium metal by pressing it between the folds of filter papers before use.
8.26 MISCELLANEOUS PREPARATIONS Several additional preparations are discussed in this section.
8.26.1 Preparation of Methyl Benzoate Carboxylic acids are converted directly to esters by the Fischer esterification method. It is an acid-catalyzed esterification of a carboxylic acid in the presence of alcohol and a mineral acid as catalyst. Heating is necessary for the success of esterification.
The mechanism of esterification proceeds in the following steps:
244
LABORATORY MANUAL OF ORGANIC CHEMISTRY
Fischer esterification is an equilibrium reaction. The yield of the product may be
improved by using an excess of one of the reactants (excess alcohol is frequently used ) or by removing water as it is formed. Procedure: In a 100 ml round-bottomed flask, place 8 g of benzoic acid and 27 ml methanol. Add 0.7 ml of conc. sulfuric acid, mix and add a few boiling chips. Attach a water condenser and reflux the mixture for 1 hr on a steam-bath. Cool the flask and transfer the solution to a separatory funnel. Extract the ester twice with 25 ml portions of ether. Wash the combined ethereal solution with 30 ml water followed by washing with 5% sodium bicarbonate solution until neutral. Finally wash once with water. Dry the solution over anhydrous sodium sulfate, filter and remove ether on a water-bath. Distil the residue using an air condenser. Collect the distillate boiling at 198200o C. The yield is 8 g.
Question 8.41 Suggest a method for the formation of an ester in which an equilibrium of the above type is not involved?
8.26.2 Preparation of Acetanilide (Acetylation) The acetylation process is important because it provides a method for the estimation of amino- and hydroxy-groups.
Procedure: Place 10 ml of aniline, 10 ml of acetic anhydride (Note I) and 10 ml of glacial acetic acid in a dry 200 ml round-bottomed flask equipped with a reflux condenser. Mix the contents, some heat is evolved due to the reaction of acetic anhydride with aniline. Heat the flask on a Bunsen burner for 1520 min. Pour the hot mixture slowly with constant stirring on 200 ml of ice cold water taken in a beaker. Filter the solid on a Buchner funnel and wash with plenty of cold water. Recrystallize the crude acetanilide from boiling water, m.p. 115oC the yield is 10 g. Note I: Acetic anhydride is lachramatory, therefore, work in a fume hood.
8.26.3 Preparation of Aspirin (Acetylation) Aspirin is acetylsalicylic acid and was first synthesized in 1853. Acetylation of a phenol can be carried out in the presence of acetic anhydride and an acid as catalyst to obtain aspirin. The reaction follows the following mechanism:
ORGANIC PREPARATIONS
245
Aspirin reacts with sod. hydroxide solution to form a salt, sod. acetylsalicylate which is soluble in water. Aspirin is the most popular drug in the world. It lowers fever, releives pain and reduces inflammation. There is evidence available that aspirin inhibits the
production of prostaglandins ( hormone-like compounds that regulate body functions ) in the body. Procedure: Dissolve 7.5 g of salicylic acid ( o-hydroxybenzoic acid) in 11.5 g of freshly distilled acetic anhydride in an Erlenmeyer flask. Add 34 drops of conc. sulfuric acid and shake the contents thoroughly. Immerse a thermometer and heat the flask between 5060°C for 1520 min. Cool and add 100 ml water. Filter the solid at the pump on a Buchner funnel and wash it twice with cold water. Press between the folds of filter papers and recrystallize from aqueous ethanol to obtain colorless crystals of aspirin. The yield is 8.8 g, m.p. 135136°C.
Question 8.42 How will you differentiate qualitatively between aspirin and salicylic acid? Suggest a color test.
8.26.4 Preparation of p-Nitroaniline The amino group on the benzene nucleus of an aniline strongly activates both the ortho and para positions. Therefore, direct nitration of aniline leads to a mixture of both the isomers. To avoid the formation of the mixture, the activating effect of the amino group is reduced first by acetylating it. This is followed by nitration of the resulting acetanilide and finally hydrolysis of the p-nitroacetanilide to p-nitroaniline. The preparation of acetanilide will be carried out by an alternative method, than the one described in 8.26.2.
246
LABORATORY MANUAL OF ORGANIC CHEMISTRY
The preparation involves the following three steps: Step A: Preparation of acetanilide Procedure: Add 4.6 ml of conc. hydrochloric acid in a 250 ml Erlenmeyer flask containing 125 ml water and 5.1 g ( 5.0 ml) of aniline. Stir until aniline has completely dissolved as its
hydrochloride salt. To this solution add 6.9 g (6.4 ml ) of freshly distilled acetic anhydride
(Note I)
shaking it till it dissolves. Then immediately add a solution of 8.3 g of sodium acetate in 25 ml water. The sodium acetate neutralizes the hydrochloric acid to form sodium chloride and acetic acid. Shake vigorously and then cool in ice. Filter the solid on a Buchner funnel and wash with 15 ml of cold water and dry. The yield is 4.9 g, m.p. 144°C. Step B: Preparation of p-nitroacetanilide Procedure: Powder 5 g of acetanilide prepared above and dissolve in 5 ml glacial acid in a 250 ml breaker. Heat to dissolve if necessary. To the solution add 15 ml conc. sulfuric acid with vigorous stirring. Immerse the flask in a cooling mixture of ice and salt to bring the temperature to 0°C. Add dropwise from a dropping funnel a pre-cooled mixture of 2.6 g
(1.8 ml) of conc. nitric acid and 2.3 g (1.3 ml) of conc. sulfuric acid with vigorous stirring (Note I). Adjust the rate of addition so that the temperature does not rise above 10°C. After the addition is complete, allow the beaker to stand at room temperature for 30 min. Pour the contents of the flask into 150 g of crushed ice. The o-nitroacetanilide may also be formed in a small amount, being soluble, remains in solution while p-nitroacetanilide precipitates out. Filter the solid on a Buchner funnel and wash thoroughly with cold water. Recrystallize from alcohol. The yield is 5.0 g, m.p. 214°C. Step C: Preparation of p-nitroaniline Procedure: Place 2.5 g of p-nitroacetanilide and 13 ml of 70% sulfuric acid in a 100 ml round-bottomed flask and reflux the mixture for 20 min or until a test sample remains clear upon dilution with 13 times its volumes of water. Pour the hot solution into 250 ml of cold water taken in a beaker and neutralize with 10% sodium hydroxide solution. Cool and filter the yellow crystalline product on a Buchner funnel. Wash it thoroughly with water. Recrystallize from hot water. The yield is 1.6 g, m.p. 148°C. Notes I: Add a little excess of acetic anhydride. II: If available use a mechanical stirrer.
Questions 8.43 Why excess of acetic anhydride is used in the preparation of acetanilide ? 8.44 Between o-nitroaniline and p-nitroaniline, which is more high boiling ?
ORGANIC PREPARATIONS
247
8.26.5 Preparation of Mandelic Acid This is a hydroxy acid which is prepared from benzaldehyde by converting it into a nitrile and subsequent hydrolysis. The intermediate reaction between potassium cyanide and the bisulfite adduct eliminates the hazard of working with the volatile and toxic hydrocyanic acid.
Procedure: Dissolve 5.5 g of sodium bisulfite in 15 ml water by shaking it in a 125 ml Erlenmeyer flask. To the solution add 5 ml benzaldehyde, cork the flask and shake vigorouly till the oily layer of benzaldehyde is converted into the crystalline bisulfite compound. Cool to room temperature and add 7 g potassium cyanide in 13 ml of water and allow the mixture to cool. Stir again and if necessary break the lumps with a glass rod. Mandelonitrile separates as an oil. Transfer the mixture to a separatory funnel, rinse the flask with a small amount of water and ether and then shake the mixture vigorously for 1 min to ensure complete
reaction. Add 10 ml of ether, shake again and discard the aqueous layer (Note I ). Wash the ether extract with 15 ml water followed by 15 ml of saturated sodium chloride solution. Transfer the solution to a distilling flask containing 7 ml each of conc. hydrochloric acid and water. Distil on a steam-bath and collect the distillate in ice-cold receiver. After all the ether has distilled over, remove the condenser and continue heating with frequent stirring to initiate hydrolysis. Heat for 1.5 hr to complete the hydrolysis and at this stage a clear solution is obtained. Cool to room temperature. Transfer the acid solution to a separatory funnel and rinse the flask with a little ether, shake and withdraw the aqueous layer into a flask. Run the ether layer into a distilling flask containing 50 ml benzene. Extract the aqueous layer similarly with two 15 ml portions of ether and add the ethereal solution to the flask containing benzene. Distil the solution again into an ice cold receiver to remove water by azeotropic distillation. The boiling point rises as ether and water are removed. Continue heating the flask till the solution becomes clear again. Disconnect the condenser and decant the hot solution into a 250 ml Erlenmeyer flask whereby the acid separates as a solid. The yield is 5.0 g, m.p. 118119°C. Note I: Discard the aqueous layer into the drain in the sink.
248
LABORATORY MANUAL OF ORGANIC CHEMISTRY
Question 8.45 How do you eliminate the production of hydrocyanic acid in the above preparation?
8.26.6 Preparation of Anthranilic Acid Anthranilic acid is prepared by the Hoffmann bromamide ( Hoffmann rearrangement ) reaction. Phthalimide is first prepared between a reaction of phthalic anhydride and urea. For this preparation phthalimide is often employed as the starting material.
Anthranilic acid preparation requires two steps: Step A: Preparation of phthalimide Procedure: In a pestle and mortar mix thoroughly 6 g pure phthalic anhydride with 1.2 g of urea and introduce the mixture in a 200 ml long-necked round-bottomed flask. Heat the flask in an oil-bath at 130135°C. The contents melt and an effervescence commerces which gradually becomes vigorous. After 1520 min frothing starts taking place which is accompanied by a rise in temperature to 150160°C. The contents of the flask almost become solid at this stage. Remove the flame and allow to cool the flask in the oil-bath. Add 10 ml of water and break the solid. Filter at the pump. Wash with a small quantity of water and dry the product at 100°C. Recrystallize from hot ethanol. The yield is 5.1 g, m.p. 233°C. Step B: Preparation of anthranilic acid Procedure: Dissolve 10 g of sodium hydroxide in 40 ml of water in 100 ml Erlenmeyer
flask and cool the solution to 0°C in an ice-bath. To this add 8.7 g ( 2.8 ml) of bromine carefully in one lot and shake the flask gently until all the bromine has reacted. Since the reaction is exothermic keep the flask at 0°C. In another Erlenmeyer flask dissolve 7.2 sodium hydroxide in 25 ml of water and cool the solution. To the cold solution add 8 g powdered phthalimide in one portion and shake. To the cold solution add sodium hydrobromite solution prepared above and swirl the flask. The temperature may rise to 70°C. Warm the mixture to 80°C for 2 min and filter if necessary, to remove any suspended impurities. Cool this solution in an ice-bath and add 30 ml conc. hydrochloric acid slowly with constant stirring until the solution is just neutral to litmus. Transfer the mixture to a 500 ml beaker and precipitate anthranilic acid by the addition of glacial acetic acid ( Note I). Filter the anthranilic acid and wash well with cold water. Recrystallize from boiling water, dry in an oven at 100°C. The yield is 4.5 g, m.p. 145°C. Note I: Some fuming takes place during this process.
ORGANIC PREPARATIONS
249
Question 8.46 Write a mechanism for the formation of phthalimide from phthalic anhydride and urea.
8.26.7 Preparation of Phenylurea Anilinium cyanate rearranges to phenylurea at room temperature.
Procedure: Prepare a solution of 6 g anilinium hydrochloride in 80 ml of water by adding 1.8 g conc. hydrochloric acid to 4.4 a aniline in a 250 ml Erlenmeyer flask. To this add a solution of 2 g sodium cyanate in 20 ml of water and allow to stand at room temperature for 1 hr till the solid has separated out. Filter it on a Buchner funnel and wash with cold water. Dry in an oven. The yield is 4.9 g, m.p. 146°C.
8.26.8 Preparation of 2, 4-Dinitrophenylhydrazine By treatment of 2, 4-dinitrochlorobenzene with hydrazine at low temperature, the above compound is obtained.
The preparation involves the following two steps: Step A: Preparation of 2, 4-dinitrochlorobenzene Procedure: In a 100 ml round-bottomed flask fitted with an air-condenser, place 5 ml chlorobenzene and 8 ml conc. sulfuric acid. Heat the mixture on a water-bath and to this add a mixture of 10 ml conc. nitric acid and 7 ml conc. sulfuric acid. Stir the mixture during
250
LABORATORY MANUAL OF ORGANIC CHEMISTRY
addition maintaining a temperature below 100°C. After the addition is complete heat the mixture on a water-bath for 1.5 hr. Cool and pour the contents of the flask on 500 g of crushed ice taken in a one litre beaker. Filter the solid and recrystallize from hot alcohol. The yield is 7.0 g, m.p. 53°C. Step B: Preparation of 2, 4-dinitrophenylhydrazine Procedure: Dissolve 5.0 g of pure 2, 4-dinitrochlorobenzene in 10 ml of ethylene glycol
(Note I) in a 100 ml round-bottomed flask. Warm, if necessary, to obtain a clear solution. Cool the flask in an ice-bath to 10°C. Add 1.4 ml of 64% aqueous hydrazine solution dropwise with constant stirring. Addition is done at such a rate that the temperature does not rise above 15°C. When the addition is complete, add 5 ml of methanol and heat the flask on a water-bath for 1520 min. Cool and collect the solid at the pump, wash with a little methanol and dry. The yield is 4.4 g, m.p. 192193°C. Note I: Dioxane as solvent may be employed instead.
8.26.9 Preparation of 7-Hydroxy-4-Methylcoumarin Resorcinol is condensed with acetoacetic ester in the presence of polyphosphoric acid for the preparation of the title compound.
Procedure: In a 250 ml Erlenmeyer flask dissolve 2.8 g of resorcinol, 3.3 g ethyl acetoacetate in 50 ml of water. To the solution add 40 g of polyphosphoric acid and heat on a water-bath at 7080°C stirring with a thermometer. After 20 min, pour the mixture into 200 ml of water contained in a beaker. Collect the yellow solid at the suction. Wash with cold water and dry in the oven at 60°C. Recrystallize from hot ethanol. The yield is 4.1 g, m.p. 105°C.
8.26.10 Preparation of Soap from Fat Carboxylic acids with long, unbranched carbon chains are called fatty acids. Fats and oils belong to the family of esters particularly glycerol and long chain carboxylic acids. The glycerol esters of saturated acids are solids while those of unsaturated acids are liquids at ordinary temperatures and are referred to as oils. Hydrolysis of a fat in the
ORGANIC PREPARATIONS
251
presence of a base (saponification) leads to glycerol and soap, i.e., sodium salt of the long chain fatty acid. Soaps constitute just one type of detergent. A detergent is any substance employed for cleaning an object.
Where R = a long carbon chain. Procedure: In a 250 ml Erlenmeyer flask, weigh 25 g of cotton seed oil or any other fat, add 15 ml of ethanol and 6 g sodium hydroxide dissolved in 25 ml water. Heat the contents of the beaker on a water-bath maintaining a bath temperature between 8090°C. Stir the mixture frequently with a glass rod and continue heating for 1 hr. After this period add 200 ml of saturated sodium chloride solution and cool the mixture to precipitate out soap. Filter it through double the thickness of cheese cloth. Wash the soap on the cloth with 50 ml of cold water and mould it into a cake in a small china dish.
To recover glycerol ( a by-product ) slightly acidify the filtrate from above with hydrochloric acid and evaporate it to dryness. Extract glycerol with 20 ml of absolute alcohol. Decant the alcohol solution from the salt and evaporate on a hot plate. A small residue of glycerol remains. To a little soap solution add a few drops of dilute hydrochloric acid solution. What is the solid precipitate?
Questions 8.47 Describe a soap. Explain the technique salting out. 8.48 What is the reaction of soap with hard water?
8.26.11 Preparation of p-Bromoaniline Bromination of aniline leads to polysubstituted compound, i.e., 2, 4, 6-tribromoaniline as the sole product. This is due to the fact that the amino group is highly activating. However, monosubstitution may be achieved by diminishing the electron-donating capacity of the amino group. For this purpose the amino group is first converted to an acetamide with acetic anhydride to form acetanilide. The acetanilide on bromination yields p-bromoacetanilide and the acyl group is finally removed later by acidic or basic hydrolysis.
252
LABORATORY MANUAL OF ORGANIC CHEMISTRY
The preparation involves three steps: Step A: Preparation of acetanilide. Procedure: Add 4.6 g of conc. hydrochloric acid to 250 ml Erlenmeyer flask containing 125 ml water and 5.1 g (5.0 ml) of aniline. Stir until aniline has completely dissolved. To
this solution add 6.9 g (6.4 ml) of freshly distilled acetic anhydride shaking till the solution is clear. Immediately pour the contents of the flask into a solution of 8.3 g of sodium acetate in 25 ml of water. Shake vigorously and then cool in ice. Filter the solid on a Buchner funnel and wash with 15 ml of cold water and dry in air. The yield is 4.9 g, m.p. 114°C. Step B: Preparation of p-bromoacetanilide Procedure: Take 3.4 g of acetanilide in a 250 ml Erlenmeyer flask and dissolve in 25 ml of acetic acid. In a second flask dissolve 1.3 ml (4.2 g) of bromine in 10 ml of acetic acid
(Note I). Add the bromine solution gradually with constant stirring to the acetanilide solution over a period of 5 min keeping the flask cooled in ice-bath. The bromine color disappears and crystals begin to appear. Allow the flask to stand at room temperature for 30 min. and then pour the contents into 250 ml of water. Stir the mixture well, and cool and add 12 g of sodium bisulfite to remove any excess bromine. Filter the solid on a Buchner funnel, wash thoroughly with water. Recrystallize from ethanol. The yield is 4.5 g, m.p. 167°C. Step C: Preparation of p-bromoaniline Procedure: Place 4 g of p-bromoacetanilide in a 100 ml round-bottomed flask and to this add 35 ml of 5 N hydrochloric acid. Fix a reflux condenser and allow the mixture to boil until all the solid has dissolved. Reflux for another 1520 min. Cool the solution in ice and carefully add 25% of sodium hydroxide solution to make it just alkaline (Note II ). The p-bromoaniline soon separates out. Filter the solid and recrystallize from hot alcohol. The yield is 3.1 g, m.p. 66°C. Notes I:
Work carefully with bromine in the fume hood.
II: Use a pH paper.
Question 8.49 Write a mechanism for the acid hydrolysis of p-bromoacetanilide to p-bromoaniline.
Chapter
9
SPECTROSCOPIC METHODS
The analytical methods discussed in the earlier chapters have been available to organic chemists since long, and undoubtedly have proven of immense value in the identification and structure determination of organic compounds. These are, however, exceedingly time consuming and the information obtained is often inconclusive. Nowadays various spectroscopic methods have greatly facilitated the analysis and they supplement the classical methods. Spectroscopy is a technique for the measurement of the amount of radiation absorbed by the substance at various wavelengths. The spectrum evolves useful information about the functional group and the molecular structure. Only two techniques, namely,
infrared ( i.r.) and nuclear magnetic resonance (n.m.r) will be discussed because these are probably readily available and in conjunction with the wet analysis often provide sufficient information to complete the structural identification of molecules. The spectroscopic methods possess the added advantage in that the measurements can be made in a short time with a very small amount of the material.
9.1 INFRARED SPECTROSCOPY (i.r.) This technique is being used most widely for the identification of organic compounds since the early 1950s. The spectrum is usually very complex and it identifies the functional group in a molecule as well as the type of bonding between various atoms. Organic molecules are not rigid; they rather continuously undergo vibrational and rotational motions. The
molecular vibrations are of two types, namely, stretching and bending (Fig. 9.1) . These vibrations have certain frequencies which are related to the masses of the atoms involved and upon the type of chemical bonding joining the atoms. These frequencies of molecular vibrations correspond to the infrared radiation. When the frequency of radiation corresponds to certain characteristic frequency of molecular vibration, light is absorbed. It is thus possible to identify the functional group from the appearance of the absorption bands. For a molecule to absorb infrared radiation there is a requirement that absorption of energy should result in a net change in the dipole moment of the molecule. Thus carbon monoxide, but not bromine or iodine, absorbs infrared light.
254
LABORATORY MANUAL OF ORGANIC CHEMISTRY
Fig. 9.1: Vibrational modes of groups of atoms.
The infrared region of the electromagnetic spectrum of interest to the organic chemist
occurs rather in a narrow range, i.e., 2 µ (4000 cm1) to 15 µ (666 cm1), 1 µ = 10 4 cm
(10, 000 Å) and is capable of providing useful information. Both wavelength and frequency are commonly used to describe an infrared absorption. The conversion of wavelength to frequency can be affected by the following equation:
(
)
v cm 1 =
104 ( ë in ì )
9.1.1 Instrumentation An infrared instrument may be designed either on a single beam or a double beam principle. A single beam spectrometer consists of a radiation source, an electrically heated carborundum rod, a Nernst filament which is passed through the sample and the emergent beam that is dispersed by a monochromator into its individual wavelengths. The spectrum is then scanned on a special chart paper. A double beam instrument works on a similar principle, except that the original radiation is divided into two beams, one of which passes through the sample while the other through a reference cell. Such an instrument records the difference in the intensities of the two beams.
9.1.2 Preparation of Sample The handling of sample for recording its infrared depends on the physical state of the compound, i.e., whether gas, liquid or solid. A gas sample is placed in a gas tight cell. The cell is made of potassium bromide or rock salt and examined directly. Potassium bromide is transparent in the infrared region. The contact of a cell with moisture must be scrupulously avoided, otherwise it becomes cloudy and transmits very little light. Since glass absorbs strongly in the useful infrared region, it cannot be used for the optical part of a spectrophotometer. Liquid samples that are non-volatile are generally examined as a thin film between two potassium bromide salt plates. One or two drops of the sample are placed between the plates, rubbed uniformly and then placed in the path of light. Solids are generally handled on a pellet produced from a sample and dry potassium bromide in a hydraulic press. The infrared spectra of solids as well as liquids may also be run as solutions in a suitable solvent. The concentration range employed is usually between 2 to 10% by weight. The choice of the solvent depends on the solubility of the sample and characteristic absorptions of the solvent. It is very much desirable to use a solvent having the least
255
SPECTROSCOPIC METHODS
amount of absorption in the i.r. region, solvents often employed are carbon tetrachloride, chloroform and carbon disulfide etc. The solvent used should be completely dry. In addition to the sample cell, a reference cell filled with the same solvent is placed in the reference beam of the instrument. If the solvent absorbs weakly in a given region of the spectrum, its absorption may be cancelled out.
9.1.3 Interpretation of Spectra An infrared spectrum is a plot of wavelength (in µ) or frequency (wave number) as abscissa and a function measuring the absorption of the compound at various wavelengths as ordinate. This function is the percent transmittance, i.e., I/Io × 100 where I is the intensity of light passing through the sample, Io is the intensity of the incident light. The region of maximum absorption, therefore, appears as valleys in the spectrum. An infrared spectrum is usually complex because of the multitude of vibrations that can occur in a molecule containing several atoms and bonds. The interpretation of the spectrum commences with the examination of the major bands (see Table 9.1). The region extending from 7 to 11 µ is often referred to as the fingerprint region of the spectrum. It is characteristic and unique for every compound. In this region the spectra of two dissimilar compounds particularly
differ. A perfect similarity in this region and in other parts of the spectrum (i.e., the spectra are completely superimposable) indicates that the two organic molecules are identical. Comparison of spectra of unknown compounds with those of known compounds can thus be one very useful technique for structure determination. Let us consider the spectrum of 2-butanol
(Fig. 9.2). It shows
absorptions owing to C O and O H stretching vibrations at 1120 cm 1 (8.92 µ) and 3350 cm1 (2.98 µ), respectively, in addition to the hydrocarbon chromophoric groups present.
Fig. 9.2: Infrared spectrum of 2-butanol.
256
LABORATORY MANUAL OF ORGANIC CHEMISTRY
The strong absorption at 3350 cm1 (2.98 µ) is typical of the polymeric association of hydroxyl groups. The non-bonded absorption peak is barely perceptible. If the infrared spectrum is run in a very dilute solution of alcohol in carbon tetrachloride in order to decrease the
chances of hydrogen bond, the band would appear at a shorter wavelength ( higher energy) due to the stretching mode of a free hydroxyl group. The stretching mode of hydrogen bonded OH bonds occurs at a lower energy. Figure (9.3) represents a spectrum of cyclohexanone
In this spectrum,
stretching appears at 1715 cm1 (5.83 µ). The position of absorption is sensitive to ring size and to the degree of conjugation. Thus in cyclopentanone, the
group absorbs at 1751 cm1
(5.7 µ) i.e., at a higher wave number. In case of conjugation, absorption occurs at a lower wave number thus methyl tolyl ketone, absorbs at 1675 cm1 (5.95 µ).
Fig. 9.3: Infrared spectrum of cyclohexanone.
Fig. 9.4: Infrared spectrum of benzamide.
257
SPECTROSCOPIC METHODS
Another example which demonstrates the utility of i.r. is that of benzamide (Fig. 9.4) . The NH stretching absorptions appear as two bands at 3356 cm 1 3110 cm1 ( 3.182 µ) . The
( 2.98 µ )
and
O stretching appears at 1670 cm1 (5.98 µ).
C
Table 9.1: Characteristic Infrared Absorptions of Selected Functional Groups Functional group
Range µ
v ( cm 1)
3.38 3.51
2962 2853
3.29 332
3040 3020
CH (alkyne, C=CH)
3.03
3300
CH (aromatic)
3.30
3030
2.74 2.79 2.72 3.12
3650 3590 3650 3200
2.77 3.12
3600 3200
CºC (alkyne )
5.95 6.17
1680 1620
C=C ( aromatic)
6.25 6.67 4.57 4.76
1600 1500 2260 2100
5.68 5.92
1300 1050
CH (alkane, CH3) CH ( alkene, C=C= C
H H
)
OH (monomeric alcohols, phenols) Hydrogen bonded NH (amines)
C=C ( alkene)
C
O (aldehydes, ketones,
carboxylic acid, esters)
C
O (carboxylic acids )
5.80 5.88
1760 1690
C
O ( esters)
5.71 5.76
1725 1750
C
O (aldehydes)
5.87 5.95
1750 1735
C O (ketones ) g -lactone C NO2 C Cl
5.80 5.87
1705 1680
5.62 5.68 6.37 6.67 12.5 16.7
C Br
16.6 20.0
1725 1705 1780 1760 1760 1690 800 600 600 500
3.82 3.92
500 2600 2550
CI SH
~ 20
258
LABORATORY MANUAL OF ORGANIC CHEMISTRY
9.2 NUCLEAR MAGNETIC RESONANCE SPECTROSCOPY (n.m.r.) The absorption of radio frequency radiation by nuclei is termed as nuclear magnetic resonance and this technique generally became available since early 1960. It has proved to be a powerful technique for structural studies and more so than even infrared spectroscopy. All nuclei possess charge and mass but nuclei of certain atoms possess nuclear spin. A hydrogen atom, for instance, having an uneven number of protons and neutrons in the nucleus, has a spin number I = 1/2. This spinning nucleus may be envisaged as a spinning top with an axis passing through the center (Fig. 9.5). Such a nucleus thus behaves as a tiny magnet and possesses magnetic moment.
Fig. 9.5: Spinning of a nucleus in magnetic field.
When the spinning nucleus is placed in an external magnetic field H 0, the magnetic dipole may either orient with or against the field. The former orientation is a state of high energy while the latter that of low energy. The axis of the spinning proton under the influence of the external field precesses about the axis of the applied field. The frequency, w of precession is given by: ω 0 = γH 0 = 2 πν 0
where g is a constant known as the magnetogyric ratio (a fundamental nuclear constant ) for the hydrogen nucleus and v0 is the frequency of precession. The frequency w thus increases as H0 increases. If electromagnetic radiation of frequency n is applied at right
259
SPECTROSCOPIC METHODS
angles to the applied field, the applied frequency is said to be in resonance with the processional frequency when w = n . At this stage the radiation is absorbed by the nucleus and it undergoes a flip to the next higher energy level. An absorption peak is obtained which can be detected electronically and recorded as a peak on a chart. This is achieved experimentally by applying frequencies which in the case of proton are in the radio frequency
range, generally 60 MHz ( mega Hertz) and corresponds to a wavelength of 5 × 102 cm at a magnetic field of 14,092 gauss. The condition of resonance for a proton can be achieved either by holding H 0 constant and varying n or by maintaining n at a constant value and changing H0. The latter approach, however, is more convenient. Nuclei that have spin and are important to an organic chemist are 1H, 13C, 19F, etc. Most n.m.r. studies have been carried out on hydrogen (proton ) nuclei and the technique is thus referred to as proton
magnetic resonance (p.m.r. or H n.m.r.). In an n.m.r. spectrum an absorption peak is obtained for each type of proton in the molecule and at a different frequency of resonance. This depends on the environment in which the nuclei are present, i.e., the neighbouring nuclei and electrons. A proton in a molecule is surrounded by a cloud of electronic charge. In a magnetic field the electrons orient in such a way that their motion induces a magnetic moment that ordinarily opposes the applied field. As a result the nucleus is exposed to an effective field that is somewhat
smaller (but in some cases larger also) than the external field. In other words, the net magnetic field is slightly less than the applied field. Since the nucleus experiences a smaller field it is said to be shielded. A higher magnetic field must thus be applied to achieve resonance. This gives rise to chemical shift which is described as the difference in the absorption position of a particular proton of a sample from that of the reference proton. There are several types of reference compounds but for protons the positions of the absorption peaks are noted with reference to tetramethylsilane (TMS) a volatile liquid, b.p. 26.4°C used as an internal standard. For this compound a single sharp resonance line occurs at the highest field end of the range of observed proton shifts where it is unlikely to obscure any other proton resonance arising from the sample. This standard is assigned a chemical shift of 0 Hz.
The chemical shift of a proton is determined in units of cps, depending on the oscillator frequency. It has been found convenient to convert such shift into frequency independent units, expressed as delta (d ):
Chemical shift in cps 6 d = Oscillator frequency in cps × 10
260
LABORATORY MANUAL OF ORGANIC CHEMISTRY
The d values are expressed as parts per million (ppm). An alternative scale is tau (t) scale. TMS is assigned an arbitrary value of 10.00. To convert a chemical shift given on the delta scale to tau scale, simply subtract the shift as measured on the delta scale from 10, i.e.,
t = 10.00 – d The chemical shifts (t) for a wide variety of hydrogens are given in Table 9.2.
Fig. 9.6: Diagram of nuclear magnetic resonance spectrometer.
9.2.1 Instrumentation and Sample Handling The sample is mixed in a glass tube whose internal diameter is 23 mm. A few drops of TMS are added and the tube is then placed in the sample holder between the pole faces of a dc electromagnet (Fig. 9.6 ) spaced 1.75 inches apart. The radio frequency single produced by the resonating nuclei is detected by means of a coil that surrounds the sample. The sample holder is rotated which serves to average out the effects of inhomogenities; sharper lines are obtained as a consequence.
261
SPECTROSCOPIC METHODS
Table 9.2: Typical Chemical Shifts of Hydrogens Chemicals shift t
(ppm d)
RCH3
9.1
0.9
R2CH2
8.7
1.3
R3CH
8.5
1.5
4.5 5.4
4.6 5.9
1.5 4
6 8.5
C=CCH3
8.3
1.7
C=CCH3
8.2
1.8
CICH
6.7
3.4
Cl2CH
4.2
5.8
BrCH
6 7.5
2.5 4
O2NCH
5.4 5.8
4.2 4.6
6 6.7
3.3 4
5.9 6.3
3.7 4.1
7 38
2 2.7
01
9, 10
4.5 9 26
1 5.5 4 12
2 to 0.5
10.5 12
59
15
0.1
10.1
C=CH ArH
OCH (alcohol, ether) OCH (esters)
RCH R O RCH ROH ArOH O RCOH RNH2 O ArCH
262
LABORATORY MANUAL OF ORGANIC CHEMISTRY
9.2.2 Interpretation of Spectra Let us consider the spectrum of anisole to demonstrate the utility of n.m.r. technique. The hydrogens of the OCH3 groups are chemically equivalent thus a single peak appears at 6.92 t. The signals down field are those of the aromatic ring. The ortho protons being closer to OCH3 groups are more shielded than meta and para protons and thus appear downfield. After the spectrum is determined it is integrated to estimate the relative number of protons in each absorption.
Fig. 9.7: NMR spectrum of anisole.
The integral tracing is recorded from left to right. The height to which the tracing rises for each group of protons is proportional to the area enclosed by each peak, and therefore, to the number of protons. The spectrum of ethanol ( neat) is shown below (Fig. 9.8 ). As is evident from the structure of ethanol it contains three types of protons and they absorb at different τ values
and correspond to OH (4.63 t), CH2 (6.58 t) and CH3 (8.83 t) . The area beneath each peak corresponds to a numerical ratio of 1 : 2 : 3. Thus n.m.r. is a convenient measure of not only the type but also the number of different protons in the molecule.
SPECTROSCOPIC METHODS
263
Fig. 9.8: NMR spectrum of ethanol (CH 3CH 2OH).
If the spectrum of ethanol is recorded under high resolution (Fig. 9.9) it is found that the spectrum is split, i.e., each peak is split into several peaks. Thus methyl group is split into a triplet and the methylene group into a quartet. This splitting is attributed to the fact that the magnetic field of one set of nuclei is influenced by the spin arrangements of the nuclei in the neighbouring group. In other words, there is a small interaction or coupling between the two groups of nuclei. This phenomenon is known as spin-spin splitting. The
spacing (in cps) of the three components of the methyl group triplet is found to be equal to the spacing of the four components of the methylene group quartet. This spacing is referred to as coupling constant, J, and is a measure of the effectiveness of coupling between two protons with different chemical shifts.
Fig. 9.9: NMR spectrum of ethanol under high resolution.
264
LABORATORY MANUAL OF ORGANIC CHEMISTRY
Figure 8.10 represents the spectrum of a-bromobutyric acid, CH3CH2CHBrCOOH and
demonstrates the splitting by neighbouring protons. Methyl protons appear at 8.92 (triplet),
methylene protons at 7.93 (quintet) and the methene protons at a lower field at 5.77 (triplet). At interesting feature is the carboxyl proton which appears at t = 10.97 ppm
( 0.97 t). Carboxylic acids usually absorb in the region 2.0 to 0.5 t.
Fig. 9.10: NMR spectrum of a-bromobutyric acid.
Questions 9.1 What is the importance of fingerprint region in i.r.? 9.2 What is the purpose of TMS in n.m.r.? 9.3 A compound with the molecular formula C7H6O2 has the following i.r. and n.m.r. spectra. Propose a structure.
SPECTROSCOPIC METHODS
265
266
LABORATORY MANUAL OF ORGANIC CHEMISTRY
9.4 The n.m.r. spectrum of compound with molecular formula C 2 H3 Cl 3 is shown below, suggest a suitable structure.
9.5 An aromatic compound with molecular formula C 10H12O2 gives the hydroxamic acid test and on acid hydrolysis yields C 8H10O and C 2H4 O2 . The n.m.r. spectrum is given below. Suggest a structure for this compound.
SPECTROSCOPIC METHODS
267
9.6 In the following two n.m.r spectra, one corresponds to 3-methyl-3-hydroxy-2-butanone and the other to 2-methyl-3-butyn-1-ol. Find out which is which.
This page intentionally left blank
SELECTED REFERENCES
1. R.L. Shriner, R.C. Fuson and D.Y. Curtin, The Systematic Identification of Organic Compounds, 5th edn., John Wiley, New York (1964). 2. N.D. Cheronis and J.B. Entriken, Identification of Organic Compounds, 2nd edn., John Wiley, New York (1963). 3. D.J. Pasto and C.R. Johnson, Organic Structure Determination, Prentice-Hall, Englewood Cliffs, N.J. (1969). 4. K.T. Finley and J.Wilson, Laboratory Manual in Fundamental Organic Chemistry, Prenticehall, Englewood Cliffs, N.J. (1970). 5. (a) P.E. Fanta and C.S Wang, Limitations of Hinsberg Method for Primry Amines, J. Chem. Educ. 41, 280 (1964). (b) C.R. Gambill, T.D. Roberts and H. Shechter, ibid, 49, 287 (1972). 6. M. Veera and Gaspario, Detection and Identification of Organic Compounds, Plenum Press, New York (1971). 7. H.T. Clark A Handbook of Organic Analysis, Longman, Rochester, N.Y. (1966). 8. A.I. Vogel, Qualitative Organic Analysis, Longman (ELBS). London (1972). 9. J.R. Dyer, Applications of Absorption Spectroscopy of Organic Compounds, Prentice-Hall, Englewood, N.J. (1969). 10. R.M. Silverstein and G.C. Bassler, Spectroscopic Identification of Organic Compounds, 2nd edn., John Wiley, New York (1967). 11. L.J. Bellamy, The Infrared Spectra of Complex Organic Molecules, 2nd edn., John Wiley, New York (1958). 12. K. Nakanishi, Infrared Absorption Spectroscopy, Holden-day, San Franciso (1962). 13. L.M. Jackman and S. Sternhall, Nuclear Magnetic Resonance Spectroscopy, 2nd edn., Pergamon Press, New York (1969). 14. A.I. Vogel, Elementary Practical Organic Chemistry, Part I, 2nd edn., Longman, London (1966).
270
LABORATORY MANUAL OF ORGANIC CHEMISTRY
15. G.Brieger, A Laboratory Manual for Modern Organic Chemistry, Harper and Row, New York (1969). 16. P.T.S. Law and M.Kestner, Preparation of Heterocyclics, J. Org. Chem. 33, 4426 (1968). 17. D.L. Pavia, Caffeine Isolation J. Chem. Educ. 50, 791 (1973), also see R. O. Connor, J. Chem. Educ. 42, 492 (1965). 18. K.L. Lockwood, Solvent Effect on Keto-Enol Equilibrium of Acetoacetic Ester, J. Chem. Educ. 42, 481 (1965). 19. R.K. Bansal, A Textbook of Organic Chemistry, 5th edn., New Age International, New Delhi (2007). 20. G.K. Helmkamp and H.W. Johnson, Jr., Selected Experiments in Organic Chemistry, W. H. Freeman and Co., San Francisco (1964). 21. R.Q. Brewster, C.A. Vanderwerf and W.E. McEwen, Unitized Experiments in Organic Chemistry, 2nd edn., Van Nostrand, New York (1964). 22. W.P. Sorenson and T.W. Campbell, Preparative Methods of Polymer Chemistry, John Wiley, New York (1963). 23. P. Yates and P. Eaton, Lewis-Acid Catalyzed D. A. Reaction, J. Am. Chem. Soc., 82, 4436 (1960); Also see R.K. Bansal, A.W. McCulloch, P.W. Rasmussen and A.G. Mclnnes, Canad, J. Chem. 53, 138 (1975). 24. K.B. Wiberg, Laboratory Techniques in Organic Chemistry, McGraw-Hill, New York (1960). 25. J. Casanova, Relative Rates of Electrophilic Substitution J. Chem. Educ., 41, 341 (1964). 26. R.M. Roberts, L.B. Rodewald and A.S. Wingrove, An Introduction to Modern Experimental Organic Chemistry, Holt, Rinehart and Winston, New York (1985). 27. J.A. Moore and D.L. Dalrymple, Experimental Methods in Organic Chemistry, P.A., (1976). 28. J.W. Hass, J. Chem, Educ., 61, 346, (1974). 29. R.K. Bansal, Organic Reaction Mechanisms, 3rd edn., Tata McGraw-Hill, New Delhi (1998). 30. E.L. Skan and J.C. Arthur, Jr., in Techniques of Chemistry, A. Weissberger and B. W. Rossiter. Ed., Wiley Interscience, New York (1971), Vol. 1, Part 5. Chapter 3. 31. L.M. Harwood, C.J. Moody and J.M. Percy Experimental Organic Chemistry, 2nd edn. Blackwell Scientific Publications, Oxford, Lodon, (1999). 32. J.W. Lehman, Multistep Operational Organic Chemistry, Prectice Hall, Inc. Upper Saddle River, New Jersey.
Appendix
1
PREPARATION OF REAGENTS
1. Isothiouronium chloride reagent Reflux a mixture of 2 g benzyl chloride and 1.2 g of thiourea in 30 ml methanol for 30 min. Then cool the flask in an ice-bath. Collect the solid on a Buchner funnel. Wash the solid several times with small portions of ethyl acetate and dry. 2. Ceric ammonium nitrate solution Dissolve 20 g of ceric ammonium nitrate in 500 ml of warm 2 N nitric acid. 3. Lucas reagent Dissolve with cooling 136 g of anhyd. zinc chloride in 89 ml of conc. hydrochloric acid. 4. 2, 4-Dinitrophenylhydrazine Dissolve 2 g 2, 4-dinitrophenylhydrazine in 15 ml of conc. sulfuric acid. Add the solution to 50 ml of 95% ethanol, then dilute the mixture to 15 ml with distilled water. Mix thoroughly and filter if necessary. 5. Iodine solution Dissolve 20 g potassium iodide and 10 g iodine in 100 ml water. 6. Ammonium vanadate reagent Dissolve 30 mg of ammonium vanadate in 100 ml of water. 7. 8-Hydroxyquinoline Dissolve 2.5 g of 8 hydroxyquinoline in 100 ml of 6% acetic acid. 8. Quinhydrone reagent solution Shake about 0.5 g of p-benzoquinone with 10 ml of water and to this add a solution of 0.5 g of hydroquinone in 1015 ml water. The greenish-black crystals of quinhydrone are formed by an addition reaction. 9. Chlorine water Pass chlorine gas in cold water till a saturated solution is obtained. 10. Molisch reagent Dissolve 1 g =-naphthol in 100 ml of 95% ethanol.
272
LABORATORY MANUAL OF ORGANIC CHEMISTRY
11. Methyl orange indicator Dissolve 1 g of methyl orange in 100 ml of water. 12. Phenolphthalein indicator Dissolve 1 g phenolphthalein in 100 ml of 95% alcohol. 13. Schiff s reagent Dissolve 1 g rosaniline hydrochloride in 100 ml water and pass sulfur dioxide till the solution becomes colorless. 14. Starch solution Make a paste of 1 g soluble starch in 50 ml of boiling water with frequent stirring. Boil the mixture till a clear solution is obtained. 15. Benedicts solution Dissolve 86.5 g crystallized sodium citrate and 50 g anhydrous sodium carbonate in about 350 ml distilled water. Filter if necessary. Add a solution of 8.65 g of crystallized cupric sulfate in 50 ml water with constant stirring. Dilute to 500 ml. 16. Fluorescein test paper In can be prepared by dipping filter paper strips in a dilute ethanolic solution of fluorescein. The paper dries readily and possesses a lemon yellow color. 17. Dichromate solution Dissolve 10 g of sodium dichromate in a mixture of 75 ml water and 25 ml conc. sulfuric acid. 18 Ferric chloride solution Dissolve 1 g ferric chloride in 100 ml of distilled water. 19. Sodium hydroxide solution (aqueous) Dissolve 10 g of sodium hydroxide pellets in 100 ml water. 20. Sodium hydroxide solution (alcoholic) Dissolve 10 g sodium hydroxide pellets in 100 ml alcohol.
Appendix
2
PURIFICATION OF SOLVENTS
Acetic acid, b.p. 118°C Acetic acid is used as a reagent in halogenation reactions. Commercial acid contains traces of acetaldehyde and other oxidizable impurities. These impurities can be eliminated by refluxing the acid with 25% (by weight) of potassium permanganate solution for a period of 26 hrs. The acid is then distilled and the fraction passing at 117118°C is collected. Traces of water, if present, can be removed from the acid by treating it with triacetylborate prepared by warming 1 part of boric acid with 5 parts (by weight) of acetic anhydride and heating to 60°C followed by cooling and filtration the resulting solid. Water reacts with triacetyl borate to form boric and acetic acid. Any contact of the acid with the skin should be avoided. Acetone, b.p. 56.5°C Pure acetone is used as a solvent in many displacement and oxidation-reduction reactions. The commercial sample contains isopropyl alcohol as an impurity. Commercial acetone is refluxed with solid potassium permanganate for 45 hrs. If the purple color deodorizes, add a pinch of potassium permanganate and heat again. Distil the solvent and keep overnight over anhydrous potassium carbonate. Filter and distil again. Collect the fraction passing at 5657°C. Ethyl alcohol, b.p. 78.4°C Ethyl alcohol is used as a reagent in a wide variety of preparations. Alcohol is a mixture of 95.5% alcohol and 0.5% water. Absolute alcohol is always employed to obtain sodium ethoxide required for condensation reactions. Preparation of absolute alcohol is accomplished by treating alcohol with quicklime. In this manner 99.5% alcohol is obtained. The remaining traces of water are removed by distilling the azeotropic mixture with benzene or magnesium turnings and a crystal of iodine. Quicklime is freshly prepared by heating lumps of clean marble in a furnace and then stored in stoppered bottles. In case commercial quicklime it used is should be treated similarly before use. About 200 g freshly heated quicklime is added to 1 litre of commercial ethanol in a round-bottomed flask fitted with a reflux condenser and drying tube, and refluxed for 56 hrs on a water-bath. It is then allowed to stand overnight. The mixture is filtered though glass wool and the filtered alcohol is
274
LABORATORY MANUAL OF ORGANIC CHEMISTRY
distilled with the exclusion of moisture. The alcohol so obtained should be properly stoppered. Extremely dry ethyl alcohol is prepared by treating the alcohol obtained with magnesium turnings and iodine. The following reactions take place: 2C2H5OH + Mg Mg(OC2H5)2 + 2H2O
Mg(OC2H5)2 + H2 2C2H5OH + Mg(OH)2
One litre of alcohol is taken in a found-bottomed flask, and 3.5 of pure dry magnesium turnings and a pinch of iodine crystals are introduced into the flask and the mixture refluxed. Heating is continued till all the metallic magnesium has been converted into its ethylate. Additional amount of iodine is introduced, if necessary. The absolute alcohol is distilled off directly into a container and stoppered properly. Ethyl alcohol is a highly inflammable solvent. Benzene, b.p. 80°C Benzene is used as a solvent in the Friedel-Crafts reaction and in many organic preparations. It is also employed in chromatographic separations. The principal impurity in commercial benzene is thiophene (b.p. 84°C). Thiophene can be removed from benzene by shaking with conc. sulfuric acid (80 ml / l of benzene) in a separatory funnel. The deep yellow layer of the acid is withdrawn and the process is repeated till the acid layer is no more colored. In this process advantage is taken of the fact that thiophene is more readily sulfonated than benzene. Benzene is then washed with water to remove acid and dried over anhydrous calcium chloride. After decanting, benzene is distilled with the exclusion of moisture. Benzene may be stored for some time over sodium wire before distillation. Benzene is a highly inflammable and toxic solvent. Carbon disulfide, b.p. 46°C Carbon disulfide is used as a solvent in organic preparations and in the Friedel-Crafts reaction. The commercial grade carbon disulfide contains several unwanted sulfur compounds. To purify carbon disulfide it is first shaken with mercury metal followed by a saturated solution of mercuric chloride and finally potassium permanganate solution. It is then dried over anhydrous calcium chloride or phosphorus pentoxide overnight and distilled. Like benzene it is also inflammable and toxic. Carbon tetrachloride, b.p. 77°C Carbon tetrachloride is used in several halogenation as a solvent. Carbon disulfide is usually present as an impurity. Commercial carbon tetrachloride is shaken with about one-tenth its volume of a mixture containing concentrated solution of potassium hydroxide in ethanol at 60°C. This process is repeated twice and then washed with a small quantity of conc. sulfuric acid until the acid layer is no more colored. It is subsequently washed with water and distilled after drying over anhydrous calcium chloride. Carbon tetrachloride is useful as a fire extinguisher but in no case is to be use over sodium fire, as a violent explosion may take place.
APPENDIX
275
Chlorobenzene, b.p. 132°C This solvent is used in certain volumetric titrations and for recrystallizing sparingly soluble substances. It can be purified by a careful distillation. Chloroform, b.p. 61°C Chloroform is a reactant in the Reimer-Tiemann reaction. It contains 0.51% of ethanol added as a stabilizer. Chloroform is shaken with conc. sulfuric acid and then washed with water. It is then distilled after drying over anhydrous calcium chloride. Chloroform should never be dried over sodium wire as it may result in an explosion. Dimethylformamide, b.p. 153°C Dimethylformamide is used as a solvent in the Gabriel synthesis, decarboxylation and Ullmann reactions. It is purified by shaking with solid potassium hydroxide in a separatory funnel and then with lime. The solvent is then distilled. Dioxane, b.p. 101°C Dioxane is used in a large number of organic reactions particularly in solvolytic displacement reactions. It is miscible with water in all proportions. It forms complexes with Grignard reagents and, therefore, cannot be used as a substitute for ether. Commercial dioxane contains water and small quantities of
acetaldehyde and glycol acetal
Glycol is hydrolyzed on keeping with the resultant
formation of peroxide. A mixture of 1 litre commercial dioxane, 13.5 ml conc. hydrochloric acid and 100 ml water is refluxed for 12 hrs. A stream of dry nitrogen gas is simultaneously bubbled to entrain acetaldehyde. The solution is allowed to cool to room temperature and solid potassium hydroxide is added till no more of it dissolves and a second layer separates out. Dioxane layer is decanted and refluxed with sodium metal for 1012 hrs and distilled. Peroxide present as impurity, if desired, can be removed by passing the distilled solvent through a column of alumina (80 g for 100200 ml of dioxane). Dioxane vapors are very poisonous. t-Butyl alcohol, b.p. 83°C It is largely employed in esterification and in the preparation of potassium t-butoxide. The alcohol can be purified first by drying over anhyd. calcium sulfate followed by distillation over calcium hydride. Ether, b.p. 34.5°C Ether is used extensively in the organic chemistry laboratory. For most purposes the commercial grade is satisfactory. Water, ethanol and peroxide present in ether can be removed to obtain anhydrous ester for specific purposes.
276
LABORATORY MANUAL OF ORGANIC CHEMISTRY
Preliminary drying is carried out by keeping ether over anhyd. calcium chloride for 24 hrs. Alcohol and water can thus be removed to a great extent. It is filtered into another clean bottle and sodium wire is introduced into it directly from the sodium press and allowed to stand for another 24 hrs. The bottle is stopped when evolution of hydrogen has ceased. Ether may be distilled on a hot plate in the hood. If it is exposed to air, slight oxidation of ether occurs with the formation of peroxide C2H5 OOC2H5. This may cause explosion if ether is distilled to dryness. The presence of peroxide in ether may be detected by the liberation of iodine (brown coloration or blue color with starch) when a small sample is shaken with an equal volume of potassium iodide (2%) solution and a few drops of dil. hydrochloric acid. Peroxides can be destroyed by shaking ether with 5% solution of ferrous sulfate which is weakly acidified with sulfuric acid. Alternatively, either can be passed over a column of alumina (80 g of alumina for 750 ml of ether) whereby the peroxide is retained by alumina. It is very important to note that while working with ether there should be no flame in the vicinity. Toluene, b.p. 110.6°C Toluene also contains sulfur compounds as impurity as does benzene. The main impurity is methyl thiophene (b.p. 112113°C). For purification 1 litre of toluene and 80 ml conc. sulfuric acid are stirred mechanically (or magnetic stirrer) at 30°C by occasional cooling. Toluene is then decanted and treated again with the acid till no more color is extracted. Finally, it is washed with water and dried over anhyd. calcium chloride and then distilled. Ethyl acetate, b.p. 77°C Ethyl acetate is used in recrystallization and in chromatographic separations. Commercial samples of ethyl acetate contain ethanol, water and acetic acid as impurities. The solvent, 100 ml of acetic anhydride and 810 drops of conc. sulfuric acid are refluxed for 4 hrs followed by distillation. Then washed with 5% solution of sodium carbonate. Finally the solvent is distilled after drying over anhyd. potassium carbonate. The last traces of water may be removed by keeping over phosphorus pentoxide. Ethylene glycol, b.p. 197°C This is a useful solvent for water insoluble organic compounds through itself it is miscible with water. It is also an excellent inert medium. Purification may be affected by distillation over sodium.
CH3OCH2CH2 Diglyme CH3OCH2CH2
O , b.p. 160°C
Diglyme (diethylene glycol dimethyl ether) is an excellent medium for reduction by diborane. It is purified by distilling from lithium aluminum hydride. Ligroin and Petroleum ether, b.p. range 40120°C These solvents (b.p. 4060°, 6080°, 80°120°C) are chiefly employed for recrystallization purposes and are obtained from petroleum. They contain some saturated hydrocarbons which through do not interfere with crystallization but are undesirable because of their reactivity. A large number of unsaturated compounds can be removed by shaking with conc. sulfuric acid. The solvent is subsequently shaken with a mixture of potassium permanganate solution and 10%
APPENDIX
277
conc. sulfuric acid to remove the oxidizable components. Finally, it is washed with water dried over anhyd. calcium and distilled. Peroxides are removed as in the case of ether by running over a column of alumina. Tetrahydrofuran, b.p. 65.4°C The solvent finds use in the preparation of Grignard reagents. It is purified by first treating with potassium hydroxide pellets followed by distillations over lithium aluminum hydride. Pridine, b.p. 115°C Pyridine is commonly used for acetylation. Anhydrous pyridine can be prepared by distilling commercial solvent from barium oxide. Alternatively, pyridine can be dried over potassium hydroxide pellets. Nitrobenzene, b.p. 210°C Nitrobenzene is used as a medium in the Friedel-Crafts reaction because aluminum chloride is moderately soluble in it. If it is used for recrystallization, the crystals should be washed with ether or ethyl alcohol to remove the last traces of solvent. Its vapors are poisonous. Dinitrobenzene and aniline are the main impurities present in nitrobenzene. The solvent is purified by steam distillation over dil. sulfuric acid. It is then dried over anhyd. calcium chloride and distilled again. Methanol, b.p. 64.5°C This solvent is used for recrystallization, in the preparation of sodium methoxide and esterification. Acetone and water are the principal impurities. To remove acetone or any other carbonyl impurity a mixture of methanol 0.51, furfural (25 ml) and 10% sodium hydroxide solution (80 ml) is refluxed for several hr. During heating, a resin is formed which removes all the compounds. The solvent is then fractionated. Water is present to the extent of 12%. To obtain absolute methyl alcohol, it is allowed to stand over magnesium turnings (57 g for 1 lit of alcohol) activated by iodine for several hr. After the evolution of hydrogen has ceased the mixture is transferred to a clean round-bottomed flask and refluxed for 23 hrs. Magnesium hydroxide and magnesium methoxide are formed and the alcohol is distilled with the exclusion of air. Methyl alcohol similar to ethyl alcohol is highly inflammable. Methylene chloride, b.p. 41°C. Methylene chloride is used in the Friedel-Crafts reaction as well as in Lewis acid catalyzed DielsAlder reaction. Furthermore, it may be used as a substitute for ether when desired as a solvent for extraction. Commercial solvent is washed with 5% sodium carbonate solution followed by water. It is fractionated after drying over anhyd. s-Tetrachloroethane, b.p. 146°C It is used as a solvent for recrystallization and in the preparation of thiokol. The technical solvent is warmed and stirred for 30 min with 8% conc. sulfuric acid. The upper layer is decanted and the process is repeated till no more color is extracted in the acid. It is then steam distilled, dried over anhyd. calcium chloride and distilled again.
Appendix
3
ATOMIC MASSES OF SOME ELEMENTS
Element
Atomic wt.
Element
Atomic wt.
Magnesium
(Mg)
24.31
Mercury
(Hg)
200.61
Aluminum
(Al)
26.98
Barium
(Ba)
137.36
Boron
(B)
10.02
Nitrogen
(N)
14.007
Bromine
(Br)
79.916
Oxygen
(O)
15.99
Calcium
(Ca)
40.08
Phosphorus
(P)
30.59
Carbon
(C)
12.01
Platinum
(Pt)
195.23
Chlorine
(Cl)
35.45
Potassium
(K)
Copper
(Cu)
63.54
Sodium
(Na)
22.99
Chromium
(Cr)
52.01
Silver
(Ag)
107.87
Fluorine
(F)
18.99
Sulfur
(S)
32.06
Hydrogen
(H)
Zinc
(Zn)
65.37
Iodine
(I)
126.90
Iron
(Fe)
55.85
(Pb)
103.19
Lithium
(Li)
6.94
Lead
1.008
39.102
Appendix
4
PHYSICAL CONSTANTS OF SOME COMMON COMPOUNDS
Compound
B.P. (°C)
Density (g/ml, 20°C)
Dielectric constant (A)
Hazards
Acetic acid
117.9
1.049
6.2
Acetic anhydride
140.0
1.087
20.7
Lachrymator
Acetone
56.2
0.790
20.7
Flammable
Acetonitrile
81.6
0.786
37.5
Flammable
184.0
1.021
17.8
Irritant
80.0
0.874
2.3
Benzaldehyde
179.0
1.041
23.0
Benzoyl chloride
197.0
1.219
Benzyl cyanide
233.5
1.015
Bromobenzene
156.0
1.495
5.4
3.119
3.09
Aniline Benzene
Bromine 1-Butanol (n-butyl aclohol)
117.3
0.810
Irritant
Flammable
Lachrymator
17.5
Irritant Flammable
Carbon tetrachloride
76.5
1.4601
2.2
Inflammable
Cyclohexane
80.7
0.779
1.42
Flammable
Chlorobenzene
132.0
1.105
5.63
Cyclohexanol
161.0
0.962
15.0
Cyclohexanone
156.0
0.947
18.3
39.8
1.327
8.9
Methylene chloride
Inflammble
280 1, 4-Dioxane
LABORATORY MANUAL OF ORGANIC CHEMISTRY
101.3
1.034
2.2
Flammable
Diethyl ether
34.5
0.714
4.3
Flammable
Dimethoxyethane
83.0
0.863
7.2
Flammable
N, N-dimethylformamide
157.0
0.949
36.7
Irritant
Dimethyl sulfoxide
189.0
1.101
46.7
Irritant
Ethyl acetoacetate
181.0
1.025
15.7
77.1
0.900
Ethyl acetate Glycol
5.63
Flammable
1.108
37.0
Flammable
Glycerol
290.0
1.263
42.5
Flammable
Ethanol
78.5
0.789
24.6
Flammable
n-Hexane
69.0
0.660
1.9
Flammable
Methanol
65.0
0.791
32.7
Flammable
n-Pentane
36.1
0.626
1.8
Flammable
Nitrobenzene
211.0
1.203
34.8
Phenol
182.0
1.550
Pyridine
115.5
0.982
12.4
Flammable
67.0
0.889
7.6
Flammable
110.6
0.867
2.4
Flammable
Tetrahydrofuran Toluene
9.78
Inflammable Irritant
Appendix
5
PHYSICAL CONSTANTS OF ACIDS AND BASES
Property
HCl
HNO 3
CH 3COOH
H2SO4
H3PO4
NH4OH
Molecular weight
36.5
63
60
98
98
35
Specific gravity
1.18
1.41
1.06
1.84
1.69
0.90
Molarity (M)
12
16
16
18
14.7
7.4
Normality (N)
12
16
16
36
44
7.4
Volume (ml) of the acid required to make 1 lit of app. 1M solution
84
63
62.5
56
68
134
Appendix
6
MIXTURE FOR COOLING BATHS
Mixture (Salt + ice)
Ratio (Salt + ice)
1. Crushed ice + water (water should cover the ice)
Lowest temperature (app) (°C)
0 5
2. CaCl2 . 6H2 O + ice
1 : 2.5
10
3. NaCl + ice
1:3
20
4. CaCl2 . 6H2 O + ice Dry ice + solvent
1 : 0.8 mixture
40
5. Dry ice + CHCl3
60
6. Dry ice + acetone or ethanol
75
7. Liquid nitrogen
196
SELECTED JOURNALS
1. Journal of American Chemical Society 2. Journal of Organic Chemistry 3. Journal of Chemical Education 4. Journal of Chemical Society (London) 5. Tetrahedron 6. Tetrahedron Letters 7. Annalen der Chemie 8. Berichte der Deutchen Chemischen Gesellschaft 9. Angewandte Chemie International Edition 10. Canadian Journal of Chemistry 11. Indian Journal of Chemistry 12. Australian Journal of Chemistry 13. Bulletin de la Societe Chimique de France 14. Recueil der Travaux Chiminques de Pays-Bas 15. Bulletin Chemical Society Japan 16. Gazetta Chimica Italiana 17. Helvetica Chimica Acta 18. Synthesis 19. Journal of Heterocyclic Chemistry 20. Heterocycles 21. Chemistry in Britain 22. Chemistry and Industry 23. Chemistry and Engineering News
This page intentionally left blank
INDEX
A Abderhalden drying pistol, 13 Acetamide, 95 Acetanilide, 96, 244 Acetic acid, 73 Acetophenone, 82 Acetophenonephenylhydrazone, 213 Acetylsalicylic acid, 135 Activated charcoal, 24 Adapters, 14 Adipic acid, 77, 196 Adipoyl chloride, 233 Adsorbent, 225 Alkene derivative, 116 Alkyne derivative, 116 Allyl alcohol, 64 Aluminum chloride test, 59 Amalgamated magnesium, 223 p-Aminobenzoic acid, 78 o-Aminophenol, 72 p-Aminophenol, 72 2-Amino-4-nitrodiphenylamine, 215 Ammonia evolution test, 55 Aspirin, 75, 244 p-Anisaldehyde, 84 Aniline, 91 Aniline hydrochloride, 104 Anisic acid, 78 p-Anisidine, 93 Anthranilic acid, 76, 144, 217, 221, 241, 248
Anthraquinone, 196 Aspirator, 11 Azeotrope, 17 Azeotropic mixture, 17 Azobenzene, 102, 200, 236
B Bayers test, 60 Beckmann rearrangement, 186 Beilstein test, 33 Benedicts solution, 272 Benedicts test, 46, 51 Benzamide, 96, 272 Benzanilide, 186, 190 Benzaldehyde, 82 Benzenesulfonamide, 103 Benzenesulfonic acid, 102 Benzhydrol, 200 Benzil, 192 Benzilic acid, 191 Benzilic acid rearrangement, 191 Benzoic acid, 75, 197 Benzoin, 85, 192 Benzophenone, 85, 235 Benzopinacol, 235 p-Benzoquinone, 103, 214 o-Benzoylbenzoic acid, 182 >-Benzoylpropionic acid, 184 s-Benzylisothiouronium chloride, 109 Benzyl alcohol, 66
286 Binder, 227 Biuret, 97 Biuret test, 61 Boiling chips, 17 Boiling point, 16, 119 m-Bromoaniline, 92 o-Bromoaniline, 92 p-Bromoaniline, 93, 251 m-Bromobenzoic acid, 77 o-Bromobenzoic acid, 76 p-Bromophenol, 69 o-Bromophenol, 65 m-Bromotoluene, 99 o-Bromotoluene, 99 p-Bromotoluene, 205 Bumping, 16
C Caffiene, 237 Camphor, 85, 209 Camphor oxime, 208 Cannizzaro reaction, 188 Carbylamine test, 53 Casein, 239 Catalytic hydrogenation, 223 Catechol, 70 Ceric ammonium nitrate test, 37 Chemical shift, 259 Chemical oxygen demand (C.O.D.) determination, 165 Chloral hydrate, 85 p-Chloroacetophenone, 83 p-Chloroaniline, 94 m-Chloroaniline, 92 o-Chloroaniline, 92 p-Chlorobenzaldehyde, 85 o-Chlorobenzoic acid, 762, 217 p-Chlorobenzoic acid, 79 p-Chlorophenol, 68 m-Chlorophenol, 66 o-Chlorophenol, 65 p-Chlorotoluene, 99, 216 m-Chlorotoluene, 99 o-Chlorotoluene, 99 Chroma, 224 Chromatographic methods, 224 Chromic acid test, 46 Cinnamic acid, 75, 187, 233 Cinnamyl alcohol, 67 Citral, 84 Citric acid, 74 Citronellol, 67
LABORATORY MANUAL OF ORGANIC CHEMISTRY
Claisen flask, 9 Claisen distillation head, 14 Column chromatography, 225 Condensers, 10 Liebig, 10 p-Cresol, 68 o-Cresol, 67 m-Cresol, 66 Crotonaldehyde, 81 Crotonic acid, 73 Crystallization, 23 Cyclohexanone, 194
D Dehydration, 206 Derivatives, 105 preparation of, s-benzylisothiouronium salts, 109 p-bromophenacyl esters, 111 3, 5-dinitrobenzoates, 107 2, 4-dinitrophenylhydrazones, 108 =-naphthylcarbamates, 106 p-nitrobenzoates, 106 oximes, 109 phenylhydrazones, 109 picrates, 115 semicarbazides, 108 p-toluenesulfonamides, 114 Determination of ascorbic acid concentration, 171 Determination of equivalent weight of a carboxylic acid, 147 Determination of molecular weight of a substance (Rasts method), 162 Diazotisation coupling, 53, 57, 215 p-Dichlorobenzene, 100 Dichlorocarbene, 193, 242 1, 2-Dichloroethane, 231 7, 7-Dichloro [4.1.0] heptane, 242 Diels-Alder reaction, 185 Diethylene glycol, 199 Diethylene glycol dimethyl ether, see diglyme Diglyme, 275 2, 5-Dihydroxyacetophenone, 189 Diimide, 234 2, 3-Dimethyl-1, 3-butadiene, 226 2, 3-Dimethyl-2, 3-butanol, 222 2, 3-Dimethyl-2, 3-butanone, 222 m-Dinitrobenzene, 202 2, 4-Dinitrobenzenesulfenyl chloride, 116 2, 4-Dinitrochlorobenzene, 249 2, 4-Dinitrophenylhydrazine, 44, 249
287
INDEX
1, 2-Diphenyl-5-nitrobenzamidazole, 215 Diphenylamine, 93 Diphenylmethane, 183 Distillate, 15 Distillation, 15 fractional, 18 reduced pressure, 20 simple, 16 steam, 21 2, 6-Di t-butylphenol, 232 Drierite, 25 Dropping funnel, 10 Drying agents, 25
Funnels, 10 buchner, 11 dropping, 10 hirsch, 10 separatory, 10
G Gel chromatography, 225 Gel liquid chromatography, 225 Gel filtration, 225 Geraniol, 67 Grignard reaction, 203
E
H
Ethyl benzoate, 88 Ethyl p-hydroxybenzoate, 90 Elution, 225 Eosin, 221 Erlenmeyer flask, 9 Esterification, 243 Estimations, 143 Estimation of a keto group, 150 Estimation of amino group, 156 Estimation of an aldehyde, 151 Estimation of aspirin, 240 Estimation of glycine (amino acid), 158 Estimation of hydroxyl group in alcohols, 143 Estimation of keto-enol equilibrium, 166 Estimation of methoxy group, 168 Estimation of nitrogen (Kjeldahl method), 154 Estimation of H, 164 Estimation of sulfur (Messengers method), 153 Estimation of unsaturation, 162
Haloform reaction, 237 Hinsberg test, 54 Hoffmann bromamide reaction, 248 Hydrazine, 234 Hydrocinnamic acid, 233 Hydroquinone, 214 Hydroquinone diacetate, 189 Hydroxamic acid test, 56 p-Hydroxybenzaldehyde, 81 5-Hydroxy-1,3-benzoxazol-2-one, 214 m-Hydroxybenzoic acid, 79 p-Hydroxybenzoic acid, 79 7-Hydroxy-4-methylcoumarin, 250 8-Hydroxyquinoline, 270
F Fehlings solution, 160 Ferric chloride test, 61 Ferrous hydroxide test, 52 Finger print region, 255 Fischer-indole synthesis, 212 Eluorescein test paper, 271 Fluorescein, 220 Flasks, 8 Formalin test, 58 Fractional distillation, 18 Friedel-Crafts reaction, 181 Fries rearrangement, 189 Fuchsine (p-rosaniline hydrochloride), 45
I Ideal solution, 17 Indophenol, 42 Infrared spectroscopy, 253 Interfacial polymerization, 233 Iodine solution, 270 Iodoform, 100, 237 Iodoform test, 46 p-Iodonitrobenzene, 216 s-Benylisothiouronium chloride, 110
K Keto-enol tautomerism, 166 Kjeldahl's flask, 155
L Lassaign's test, 32
288 Liebermann reaction, 42 Liebig's condenser, 10 Ligroin, 275 Linalool, 65 Liquid-liquid chromatography, Liquid-liquid partition chromatography, 224 Litmus paper test, 49 Lucas reagent, 270 Lycopene, 238
M Magnetic spinner bar, 12 Magnetic stirrer, 12 Magnetogyric ratio, 258 Mandelic acid, 75, 247 Mannitol, 71 Mechanical stirrer, 13 Melting point, 117 Menthone, 83 Messenger's method, 153 p-Methylacetophenone, 83 Methyl benzoate, 87, 243 Methyl p-hydroxybenzoate, 90 Methyl orange, 218 Methyl oxalate, 88 Methyl phenyl acetate, 88 Methyl red, 221 Methyl salicylate, 88 Mixed melting point, 117 Molisch reagent, 270 Molisch test, 50 Monomer, 230 Mother liquor, 25
N =-Naphthol, 69 >-Naphthol, 53, 71 =-Naphthoic acid, 77 >-Naphthylamine, 94 =-Naphthylamine, 93 =-Naphthylcarbamate, 106 Ninhydrin, 229 p-Nitroacetanilide, 245 p-Nitroacetophenone, 202 o-Nitroaniline, 94 m-Nitroaniline, 94, 202 p-Nitroaniline, 95, 245 o-Nitroanisole, 101 p-Nitroanisole, 102 p-Nitrobenzamide, 97
LABORATORY MANUAL OF ORGANIC CHEMISTRY
Nitrobenzene, 101 m-Nitrobenzaldehyde, 85 o-Nitrobenzaldehyde, 84 p-Nitrobenzoic acid, 79, 195 m-Nitrobenzoic acid, 76 o-Nitrobenzoic acid, 76 o-Nitrophenetole, 102 p-Nitrophenetole, 102 o-Nitrophenol, 69, 102, 178 m-Nitrophenol, 70 p-Nitrophenol, 70, 102, 178 p-Nitrotoluene, 102, 195 o-Nitrotoluene, 101 Norit, 24 Nuclear magnetic resonance spectroscopy, 258 Nylon, 233
O Olfaction, 27 Optical activity, 209 Ordinary funnel, 10 Oxalic acid, 74 Oxamide, 98 Oxidation and reduction, 194
P Paper chromatography, 229 Partition chromatography, 2 Perkin reaction, 187 Phenol, 68 Phenol-formaldehyde resin, 231 Phenolphthalein preparation, 219 Phenolphthalein test, 42, 49 Phenylacetamide, 96 Phenyl acetate, 87 Phenylacetic acid, 74 Phenyl benzoate, 90 Phenyl cinnamate, 90 =-Phenylethyl alcohol, 66 =-Phenylethylamine, 210 Phenylhydrazine, 212, 213 2-Phenylindole, 212 1-Phenyl-3-methyl-5-pyrazolone, 213 Phenyl salicylate, 89 Phenyl urea, 249 Phloroglucinol, 72 Photochemical reaction, 235 Phthalein test, 42 Phthalic acid, 78
289
INDEX
Phthalimide, 97, 248 Picric acid, 179 Pinacol, 223 Pinacol-pinacolone rearrangement, 222 Picric acid, 71 Pinacolone, 223 Piperine, 239 Pipettes, 9 graduated, 9 Pasteur, 9 Pivalic acid, 198 Polarimeter, 209 Polymer, 230 Polyphosphoric acid, 212 Polystyrene, 232 Potassium ferrocyanide test, 61 Preparation of o-and p-nitrophenols, 178 Preparation of diphenylmethane, 183 Preparation of nitrobenzene (nitration), 176 Preparation of picric acid, 179 Preparation of 2, 4, 6-tribromoaniline (Bromination), 179 Pyrogallol, 71
Q Quinhydrone, 72 Quinhydrone reagent, 270 Quinol, 72 Quinoline, 211
R Rast's method, 173 Reducing sugar, 159 RF value, 227 Reimer-Tiemann reaction, 193 Relative rates of electrophilic aromatic substitutions, 180 Resorcinol, 70 Rochelle salt, 159
S Salicylaldehyde, 82, 193 Salicylamide, 96 Salicylic acid, (o-hydroxybenzoic acid), 244 Salting-out effect, 11 Sandmeyer reaction, 216 Saponification value, 161 Schiff's reagent, 271 Schiff's test, 45
Schötten-Baumann reaction, 190 Seeding, 24 Separatory funnel, 10 Simple distillation, 15 Silver diamine complex, 34, 44 Silver salt method, 147 Skraup synthesis, 211 Soap, 250 Sodium bicarbonate test, 49 Sodium borohydride, 203 Sodium fusion extract, 31 Solubility, 29 Soxhlet apparatus, 239 Specific rotation, 209 Spectroscopy, 253 Spin-spin splitting, 263 Starch solution, 271 Steam distillation, 22 Stillhead, 14 Stirrers, 12 Styrene, 232 Succinic acid, 78 Succinimide, 98 Sulfanilic acid, 104
T Tartaric acid, 78 Tautomers, 166 Test for anilide group, 57 Terpineol, 68 Tetralin, 234 Tetramethylsilane, 259 Theoretical plate, 19 Thermocole, 232 Thiele tube, 118 Thin layer chromatography, 227 Thiokol rubber, 231 Thiourea, 61 Tollens test, 44 p-Toluic acid, 205 o-Toluenesulfonamide, 104 p-Toluenesulfonamide, 103 p-Toluenesulfonyl chloride, 103 m-Toluic acid, 75 o-Toluic acid, 74 p-Toluic acid, 78, 205 o-Toluidine, 92 p-Toluidine, 93 m-Toluidine, 91 Toxic chemicals, 3 Toxicity, 4
290 2, 4, 6-Tribromoaniline, 179 2, 4, 6-Tribromophenol, 40 Triethylene glycol, 199 Triethylene glycol dimethyl ether, 242 Triglyme, 242 2, 4, 6-Trinitrophenol, 179 Trimethylacetic acid, 198 Triphenylmethanol, 71, 204 Triptycene, 241
U
LABORATORY MANUAL OF ORGANIC CHEMISTRY
Vacuum distillation, 21 Vanadium oxine test, 38 Vapor pressure, 15 Vibrations, 253 bending, 254 stretching, 254 Vigreux column, 18 Vitamin C, 171
W
Urea, 61 Urea nitrate, 61 Urethane, 106
Water pump, 11 Widmer column, 18 Wiz's solution, 163 Wolff-Kishner reduction, 199
V
X
Vacuum desiccator, 13
Xanthate test, 37
