Chem_Expt 10

CLASSIFICATION TESTS FOR CARBOXYLIC ACID AND DERIVATIVES Sy, Alyssa Lyn Y., Tan, Diovic S., Taqueban, Jillian A., Torno, Katrina A., and Turbolencia, Mirzi S. Group 9 2A Medical Technology Organic Chemistry Laboratory

ABSTRACT Classification tests for carboxylic acid and derivatives include hydrolysis, alcoholysis, aminolysis, and hydroxamic acid test. The sample compounds used for the carboxylic derivatives were acetyl chloride, acetic anhydride, ethyl acetate, acetamide, and benzamide. These compounds underwent the different classification tests assigned to them: acetyl chloride and acetic anhydride (hydrolysis, alcoholysis, and aminolysis); ethyl acetate (hydrolysis and hydroxamic acid test); benzamide (hydrolysis); and acetamide (hydroxamic acid test). Positive results in these classification tests are: the formation of carboxylic acid (hydrolysis); formation of an ester (alcoholysis); formation of an amide (aminolysis); and formation of a deep burgundy discoloration indicating the presence of hydroxamic acid (hydroxamic acid test).

INTRODUCTION Carboxylic acids and their derivatives are the most abundant of all organic compounds, both in the laboratory and in living organisms. Many of the carboxylic acids play important roles in the chemistry of organisms, and a number of them are major industrial chemicals. Acid halides, acid anhydrides, esters, and amides are just some of the many different kinds of carboxylic acid derivatives. The common structural feature of all these compounds is that they contain an acyl group bonded to an electronegative atom or substituent that can act as a leaving group in substitution reactions. As strong organic acids, carboxylic acids react with silver nitrate and sodium bicarbonate to form the corresponding carboxylate salts. The chemistry of all these derivatives is similar and is dominated by a single general reaction type: the nucleophilic acyl substitution reaction. These substitutions take place by addition of a nucleophile to the polar carbonyl group of the acid derivative, followed by expulsion of a leaving group. Acid halide is the most reactive towards a nucleophile, followed by acid anhydride, ester, and the least reactive, the amide. Thus, reactions of these compounds with a given reagent vary with regard to the rate, thermochemistry, and even the completion of the reaction. Acid or acyl halides, due to their reactivity, are good starting materials for synthesis. Esters and amides are important functional groups in biomolecules like fats and proteins. The most common reactions of carboxylic acid derivatives are: substitution by water (hydrolysis) to yield an acid; by an alcohol (alcoholysis) to yield an ester; by an amine (aminolysis) to yield an amide, by hydride ion to yield an alcohol (reduction), and by an organometallic reagent to yield an alcohol (Grignard reaction).

All carboxylic acid derivatives yield the parent carboxylic acid upon reaction with water. Moreover, one derivative can be converted into another, provided the former is more reactive than the latter. The objectives of this experiment were: to differentiate the reactivities of carboxylic acid derivatives; to distinguish carboxylic acid derivatives using classification tests; and to explain through chemical equations and mechanism the reactions involved in each test.

EXPERIMENTAL A. Compounds tested (or Samples used) The following sample compounds were used in this experiment: acetyl chloride; acetic anhydride; ethyl acetate; acetamide; and benzamide. B. Procedure 1. Hydrolysis of Acid Derivatives The hydrolysis of acyl halides and acid anhydride was started by placing 1ml of water into two separate test tubes. Ten drops of acetyl chloride and of acetic anhydride were cautiously added dropwise, then, warming effect was noted on each separate test tube. The resulting mixtures obtained from the first part were divided into two portions. One ml of 2% AgNOз was added to the 1st portion in which precipitation was observed and another 1ml of saturated NaHCOз was added to the 2nd portion after which evolution of gas was noted. These additions of reagents were done on the two separate test tubes. One ml of ethyl acetate was used for the hydrolysis of esters in which 2ml of 25% NaOH solution was added to it. The test tube was covered with a marble and was heated in a boiling water bath for 5 mins. Afterwards, the

mixture was neutralized with 10% HCl solution and the odor was noted with a wafting motion. For the hydrolysis of the amides, a pinch of benzamide was treated with 5ml of 10% NaOH solution and the mixture was heat to boiling. During heating, a piece of moist red litmus paper was held over the test tube to test the reaction of the gas evolved.

acidic hydrolysis to yield carboxylic acids and alkaline hydrolysis to yield carboxylic acid salts, their rates of reaction vary. Thus, acetyl chloride with small alkyl group reacts almost explosively with water. Acetyl chloride is hydrolyzed by water to acetic acid and HCl as seen in Figure 1. O

2. Alcoholysis: Schotten-Baumann Reaction A mixture of 10 drops of acetic acid, 1ml ethanol, and 5 drops of concentrated sulfuric acid (H2SO4) was warmed over a water bath for 2 minutes. The odor of the ester formed was noted. In another mixture of 0.5ml of ethanol, 1ml water, and 0.2ml of acetyl chloride, 2ml of 20% NaOH solution was added. The test tube was stoppered or plugged with a cork or parafilm then the mixture was shaken for several minutes. The odor of the ester formed and the formation of two layers were both noted. 3. Aminolysis: Anilide Formation A few drops of acetyl chloride and of acetic anhydride were added to 0.5ml aniline. The mixture was transferred to a new test tube containing 5ml of water and the formation of precipitate was then noted. 4. Hydroxamic Acid Test A preliminary test should have been done before the test proper but the group didn’t perform this test anymore. In a preliminary test, a yellow color must be produced when 1 drop of 5% FeClз solution was added to the mixture of 2 drops of the sample, 1ml of 95% ethanol, and 1M HCl. If otherwise which means, that if a color other than yellow is obtained, the group cannot perform or cannot proceed to the test proper. Two drops of ethyl acetate and of acetamide was added to 2ml of alcoholic NH2OH∙HCl and 1ml of KOH. The mixture was heated in a boiling water bath for 2 minutes. After it was cooled, 1ml of 5% FeClз was added then; a deep burgundy color was observed which indicated the positive result.

RESULTS AND DISCUSSION 1. Hydrolysis of Acid Derivatives All carboxylic acid derivatives can be hydrolyzed under acidic conditions to carboxylic acids and under basic conditions to carboxylate ions. Cleavage by water, called hydrolysis, is a typical reaction of an acid halide with a nucleophile. Although all acid chlorides undergo

SN acyl CHз C Cl + HOH acetyl chloride O

CHзCOOH + HCl acetic acid

O

SN acyl CHзC O C CHз + HOH acetic anhydride

2 CHзCOOH acetic acid

Figure 1. Hydrolysis of acetyl chloride and acetic anhydride This unwanted reaction usually takes place when an acid chloride is stored in a container that is not carefully sealed to exclude moisture. Hydrolysis of acyl chlorides can be avoided by storing them under dry nitrogen, working under anhydrous conditions, and using dry solvents and reagents. On the other hand, acetic anhydride is not as reactive as acetyl chloride. Even though acid anhydrides undergo reactions with the same nucleophiles that the acid chlorides react with, the rate of reaction is slower. As seen also in Figure 1, acetic anhydride reacts with water to yield two acetic acids. Acetic anhydride is the most carboxylic acid anhydride. It is produced and used in large quantities in industry, primarily for the synthesis of plastics and fibers. Acetyl chloride and acetic anhydride didn’t need to be catalyzed due to their high reactivity whereas ethyl acetate and benzamide needed to be catalyzed to dissociate the proton before the tetrahedral intermediate collapse to react with water. A. Hydrolysis of Acid Derivatives acetyl chloride A.1. acetic anhydride A.2. ethyl acetate A.3. benzamide

Table 1.

Observations w/ H2O

w/ AgNOз white ppt.

w/ sat. NaHCOз warming no ppt. effect white gas warming no ppt. no ppt. effect white gas plastic-balloon like odor basic (moist red litmus paper turned to blue)

Observations on Hydrolysis of Acid Derivatives

During the hydrolysis of acetyl chloride and acetic anhydride as seen in Table 1, a warming effect was observed due to exothermal reaction and formation of the acetic acid, the parent carboxylic acid. The gas that evolved during effervescence of the addition of 2%AgNOз and saturated NaHCOз was due to the evolution of gas. The acetyl chloride when added with 2%AgNOз formed a white precipitate while acetic anhydride did not. Esters are hydrolyzed only very slowly, even in boiling water. Hydrolysis becomes considerably more rapid, however, in the presence of refluxing aqueous acid or base. Ethyl acetate was hydrolyzed using 25% NaOH solution and was neutralized with 10% HCl solution and possessed a plastic-balloon odor. Amides can be hydrolyzed under both acidic and basic conditions. However, amide hydrolysis is quite slow since this derivative exhibits high stability of the amide functional group. The resistance of carboxylic acid amides to hydrolysis is an important characteristic of the amide functional group. Proteins and peptides are large molecules made up of smaller ones joined by amide linkages, and the stability of the C (O)-NH bond is of great biochemical significance. In hydrolysis, benzamide yielded ethanoic acid and amine using 5ml of 10% NaOH solution. The reaction of the gas evolved was tested by holding a piece of moist red litmus paper over the test tube which eventually turned to blue. 2. Alcoholysis: Schotten-Baumann Reaction The cleavage of an organic compound with an alcohol is referred to as alcoholysis. Acid chlorides react with alcohols to yield esters and HCl in a reaction that is directly analogous to hydrolysis. Alcoholysis of acid chlorides is valuable for the synthesis of hindered esters and phenyl esters. Schotten-Baumann is of particular interest because it might be expected that the water and hydroxyl ion present could compete with the alcohol to be acylated and reduce seriously the yield of the product desired. One example for this is the acetyl chloride.

Esters can also be prepared by Fischer esterification—treatment of carboxylic acid with an alcohol in the presence of an acid catalyst. It is reversible, and, in order to achieve high yields of ester, there must be excess of alcohol. One example of this is the acetic acid. O CHзCOOH + CHзCH2OH

CHз C OCH2CHз + HOH

Figure 3. Fisher Esterification on acetic acid

B. Alcoholysis

Observations

acetic acid

fruity odor/plastic balloon-like odor

acetyl chloride

plastic balloon-like odor

Table 2. Observations on Alcoholysis Alcoholysis of acetyl chloride and acetic acid lead to the formation of ester as seen in Table 2. However, acetyl chloride was the faster to react due to its high reactivity towards nucleophiles. In alcoholysis of acetic acid, it yielded an ester which has a fruity odor or plastic balloon-like odor and water. In alcoholysis of acetyl chloride, it yielded an ester and HCl. There was formation of two layers which was due to the differences in solubility and density of ether and aqeous HCl. 3. Aminolysis: Anilide Formation Aminolysis of acetyl chloride and acetic anhydride yielded anilide upon addition of water. Amides cannot undergo aminolysis. Formation of a white precipitate was due to the presence of anilide in the mixture as seen in Table 3. C. Aminolysis

Observations

acetyl chloride

formation of white ppt.

acetic anhydride

formation of white ppt.

Table 3. Observations on Aminolysis: Anilide Formation

O CHзCCl + CHзCH2OH

CHзCOCH2CHз + HOH

Figure 2. Schotten-Baumann Reaction on acetyl chloride

4. Hydroxamic Acid Test In hydroxamic acid test, no catalyst is needed when the nucleophile is nitrogen. No preliminary test has been done. The hydroxamic acid is identified by formation of a red-to-purple color in Acid halide developed a fast reaction than acid amide which reacted slowly.

O

O SN acyl

RC – L + NH2OH

RC NH OH + H-L hydroxamic acid

Shriner, R.L., et al (1980). The Systematic Identification of Organic Compounds: a laboratory manual. 6th ed. New York: John Wiley & Sons, Inc.

Figure 4. General Reaction in Hydroxamic acid Test

Upon being heated with hydroxylamine, ethyl acetate and acetamide were both converted to hydroxamic acid which then resulted into the formation of magenta or deep burgundy coloration as seen in Table 4. Hydroxamic Acid Test Preliminary Test

Observations —

ethyl acetate

deep burgundy color

acetamide

deep burgundy color

Table 4.

Observations on Hydroxamic Acid Test

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