substitution reaction

TERM PAPER CHEMISTRY (CHE 101)

Topic:

SUBSTITUTION REACTIONS

DOA: SEPT 2, 2010 DOR: SEPT30, 2010 DOS: NOV10, 2010

Submitted to:

Ms. Vibhuti Walia

Submitted by:

Mr. Amandeep Singh Khera

Deptt. Of Chemistry

Roll. No. RK6005A19 Reg.No. 11000597 Class

K6005

ACKNOWLEDGEMENT

It acknowledges all the contributors involved in the preparation of this project. Including me, there is a hand of my teachers, some books and internet. I express most gratitude to my subject teacher, who guided me in the right direction. The guidelines provided by her helped me a lot in completing the assignment.

The books and websites I consulted helped me to describe each and every point mentioned in this  project. Help of original creativity and illustration had taken and I have explained each and every aspect of the project precisely.

At last it acknowledges all the members who are involved in the preparation of this project.

 Thanks AMANDEEP SINGH

ABSTRACT

In a subs substi titu tuti tio on reac reacti tion on,, a fun functi ction onal al gr grou oup p in a particu ticullar chemical compound is repla eplace ced d by ano another ther group . In organ rganic ic chem chemis istr try, y, the the electrophilic electrophilic and nucleophilic nucleophilic substitution reactions are of prime importance. After After going going throu through gh this this one one can easily easily under underst stand and what what is sub sub stitution reaction. One can account for various types of substitution reaction n there mechan mechanis ism m i.e. i.e. SN1 and and SN2. SN2. Here Here we will will take take accou account nt of subs substit tituti ution on react reactio ions ns like like nucle nucleop ophi hilic lic subs substit titut utio ion n and and electr electrop ophil hillic lic subs substit tituti ution on react reactio ions. ns. We will will talk talk about about subs substit titut uted ed compo compoun unds ds,, contr control ollin ling g ligan ligand d substitution reactions. We will talk about use of substitution reactions in day to day life and its importance. We will account for applications an d future prospective of substitutions reaction and its day to day need. We will come across how radical substitution reaction occurs n their importance. We will come across various steps required for radical substitution.

TABLE OF CONTENT

1. INTR INTROD ODUC UCTI TION ON 2. NUCLEOPH NUCLEOPHILIC ILIC SUBSTIT SUBSTITUTION UTION 3. ELECTROPH ELECTROPHILIC ILIC SUBSTIT SUBSTITUTIO UTION N

3.1 ELECTROPHILIC AROMATIC SUBSTITUTION 3.2 ELECTROPHILIC ALIPHATIC SUBSTITUTION 4. RADICA RADICAL L SUBST SUBSTITU ITUTIO TION N 5. SUBST SUBSTITU ITUTED TED COMP COMPOUN OUNDS DS 6. MECHAN MECHANISM ISM OF REAC REACTI TION ON

6.1 SN1 MECHANISM 6.2 SN2 MECHANISM 7. APPL APPLIC ICAT ATIO IONS NS 8. FUTURE FUTURE PROSP PROSPECT ECTIVE IVE 9. BIBL BIBLOG OGRA RAPH PHY Y

INTRODUCTION

In a subs substi titu tuti tion on reac reacti tion on,, a func functi tion onal al grou group p in a part partic icul ular ar chem chemic ical al compound is replaced by another group. The term substitution is derived from the word ‘substitute’ which means putting one thing in place of other In organic chemistry, chemistry, the electrophilic and nucleophilic nucleophilic substitution reactions are of prime prime importan importance. ce. Organic Organic substit substitutio ution n reactio reactions ns are classifi classified ed in several main organic reaction types depending on whether the reagent that brings about the substitution is considered an electrophile or a nucleophile, whether a reactive intermediate involved in the reaction is a carbocation, a carbanion or a free radical or whether the substrate is aliphatic or aromatic. Detai Detailed led unde underst rstand andin ing g of a reacti reaction on type type helps helps to predi predict ct the the prod produc uctt outcome in a reaction. It also is helpful for optimizing a reaction with regard to variables such as temperature and choice of solvent.

.

A good example of a substitution reaction is the photochemical chlorination of methane forming methyl chloride.

In the the abov above e reac reacti tio on Cl2 and and CH4 are are reac reacta tant nts s and and take take part part in a substitution reaction. In this reaction Cl replaces H from CH 4 in the presence of sunlight to form CH 3Cl.  There are various substitution reactions include – •

Nucleophilic substitution

•

Electrophilic substitution

•

Radical substitution

•

Substituted compound

NUCLEOPHILIC SUBSTITUTION In organic and inor inorgan ganic ic chem chemistr istry y , nucleop nucleophili hilic c substitu substitution tion is a fundame fundamenta ntall class class of substitu of substitution tion reaction in which an "electron rich" nucleophile selectively bonds with or  attacks the positive or partially positive charge of an atom attached to a group or atom called lled the group. up.

The

posit sitive ive

or

partia rtiall lly y

posit ositiv ive e

atom tom is refe eferred rred to as

an electrophile electrophile.Nucleophilic .Nucleophilic substitution happens when the reagent is a nucleophile, which which means means,, an atom atom or molec molecule ule with with free free elect electron rons. s. A nucleophile reacts reacts with with an aliphatic substrate

in

a nu nucl cleo eoph phil ilic ic

alip al ipha hati tic c

subs su bsti titu tuti tion on reac reacti tion on..

Thes These e

substitutions can be produced by two different mechanisms: unimolecular nucleophilic substitution substitution (SN1) and bimolecular nucleophilic substitution (SN 2). The SN1 mechanism has two steps. In the first step, the leaving group departs, forming a carbocation. In the second step, the nucleophilic reagent attacks the carbocation and forms a sigma bond. This This mech mechan anism ism can resu result lt in either either inver inversio sion n or retent retention ion of confi configur gurat ation ion.. An SN2 reaction has just one step. The attack of the reagent and the expulsion of the leaving group happen simultaneously. This mechanism always results in inversion of  conf config igur urat atio ion. n. When When the the subs substr trat ate e is an aromatic comp compou ound nd the the reac reacti tion on type type is nucleoph nucleophilic ilic aromatic substitution. substitution . Carboxy Carboxylic lic acid derivatives react with nucleophiles in nucl nucleop eophili hilic c acy acyll subs substitu titution tion.. This This kind kind of reac reacti tion on can can be usef useful ul in prep prepar arin ing g compounds. The most general form for the reaction may be given as Nuc: Nuc: + R-LG → R-Nuc + LG: LG :

The electron pair (: ( :) from the nucleophile (Nuc) attacks the substrate (R-LG) forming a new bond, while the leaving group (LG) departs with an electron pair. The principal product in this case is R-Nuc. The nucleophile may be electrically neutral or negatively charged, whereas the substrate is typically neutral or positively charged. An example of nucleophilic substitution is the hydrolysis of an alkyl bromide bromide,, R-Br, under alkaline conditions, where the attacking nucleophile is the OH− and the leaving group is Br -. R-Br + OH − → R-OH + Br −

ELECTROPHILIC SUBSTITUTION

Electrophilic

substitution reactions

an electrophile displaces

a

always hydrogen hydrogen.. Electrophilic

are

group

in

chemical a

aromatic

reactions

compound,

typically

substitution is

in

which but

not

characteristic

of aromatic of aromatic comp compoun ounds ds and and is an impor importa tant nt way way of introd introduc ucing ing funct function ional al group groups s onto benzene rings. The other main reaction type is electrophilic aliphatic substitution .

ELECTROPHILIC AROMATIC SUBSTITUTION – In electrophilic substitution in aromatic compoun compounds ds,, an atom appended to the aromatic ring,, usually hydrogen is replaced by an electrophile. The most important reactions of  ring this type that take plac lace are arom aromatic atic nitr nitratio ation n , arom aromatic atic halo halogena genation tion,, aromatic sulfonation and acylation and alkylating Friedel-Crafts reactions. reactions .

ELECTROPHILIC ALIPHATIC SUBSTITUTION – In electrophilic substitution in aliphatic compo ompoun und ds, an electrophile displaces a functional group. group . This reaction is similar to nucleophilic aliphatic substitution where the reac reacta tant nt is a nucleophile rather rather than than an electrophile electrophile.. Mech Mechan anis ism m is same same that that of  nucleophillic substitution reaction.

RADICAL SUBSTITUTION In free radic ica al halo log genat atio ion n reactions radical substitution takes place with halogen reag reagent ents s and and alkane subs substr trat ates es.. Anot Anothe herr impo import rtan antt clas class s of radi radica call subst substitu itutio tions ns invol involve ves s ar ary yl rad adic ical als s. One example is the hydroxylation of benzene of benzene by Fenton's reagent. reagent . Many oxidation oxidation and reduction reduction reaction reactions s in organic organic chemistry have free radical intermediates intermediates,, for example the oxidation of  aldehydes to carboxylic with ch chrom romic ic aci acid d . Cou Couplin pling g reac reaction tions s can can also also be cons consid ider ered ed radi radica call substitutions. Certain aromatic substitution takes place by radical-nucleophilic aromatic substitution.. Auto-oxidation is a process responsible for deterioration of paints and food substitution and lab hazards such as diethyl ether peroxide. peroxide . The reaction always involves at least two steps, and possibly a third. In the first step called initiation a free radical is created by homolysis homolysis.. Homolysis can be brought about by heat or light but also by radical initiators such as organic peroxides or azo or azo compounds. compounds . Light is used to create two free radicals from one diatomic species. The final step is called termination in which the radical recombines with another radical species. If the reaction is not terminated, but instead the radical group(s) go on to react further, the steps where new radicals are formed and then react is collectively known as propagation because a new radical is created available for secondary reactions.

Examples

SUBSTITUTED COMPOUNDS

Substituted compounds are chemical compounds where one or  more hydrogen atoms of a core structure have been replaced with a functional group like alkyl alkyl,, hydroxy, or halogen or  halogen..

For example benzene is a simple aromatic ring and substituted benzenes are a heterogeneous group of chemicals with a wide spectrum of uses and properties:

Compou general nd formula

Benzene C6H6  Toluene

C6H5-CH3

o-Xylene C6H4(-CH3)2

general structure

Mesityle C6H3(-CH3)3 ne Phenol

C6H5-OH

  Jus Justt a few few subs substi titu tute ted d benz benzen ene e compounds

MECHANISM OF REACTIONS

•

SN1 MECHANISM

The SN1 reaction is a sub substit stitutio ution n reac reaction tion in orga organic nic che chemist mistry ry.. "SN" stan stands ds for nucleophilic for nucleophilic substitution and the "1" represents the fact that the rate-determining step is unimolecular . The rea reacti ction involv volve es a carbocation inte interm rmed edia iate te and and is commonly seen in reactions of secondary or tertiary alkyl halides under strongly basic basic condition conditions s or, under under strongly strongly acidic conditio conditions, ns, with seco secondar ndary y or tert tertiary iary alcohols.. alcohols An example of a reaction taking place with an S N1 rea reactio ction n mec mechan hanism ism is the hydrolysis of tert-butyl bromide with water forming tert-butyl alcohol:

This SN1 reaction takes place in three steps:

•

Formation of a tert-butyl carbocation by separation of a leaving group (a bromide anion) from the carbon atom: this step is slow and reversible reversible.. [4]

•

Nucleophilic attack: attack : the carbocation reacts with the nucleop hile. If  the nucleophile is a neutral molecule (i.e. a solvent solvent)) a third step is required to complete the reaction. When the solvent is water, the intermediate is an oxonium ion. This reaction step is fast.

•

Deprotonation:: Removal of a proton on the protonated nucleophile by Deprotonation water acting as a base forming the alcohol and a hydronium ion. This reaction step is fast.

•

SN2 MECHANISM

The SN2 reaction (also known as bimolecular nucleophilic substitution or as backside attack)

is

a

type

of  nuc  nucleop leophilic hilic

substit sub stitutio ution n,

where

a

lone

pair

from

a nucleop nucleophile hile attacks attacks an electron electron deficien deficientt electrop electrophilic hilic center center and bonds to it, expelling another group called a leaving group. group . Thus the incoming group replaces the leavin leaving g group group in one one step. step. Since Since two two reac reactin ting g spec species ies are involv involved ed in the slow, ra rate te-d -det eter erm min inin ing g

ste st ep of

the reaction reaction,,

this

leads

to

the

namebimolecular nucleophilic substitution, or S N  Among inorgan inorganic ic chemists chemists,, the 2 N2    .  Among SN2 reaction is often known as the interchange mechanism. The

reaction

most

often

occurs

at

an aliphatic sp3 carbon

center

with

an

electronegative, stable leaving group attached to it - 'X' - frequently a halide atom. The breaking of the C-X bond and the formation of the new C-Nu bond occur simultaneously to

form

a tr trans ansiti ition on

state sta te in

which

the

carbon

under

nucleophi lic lic

atta attack ck

is pentaco pentacoordi ordinate nate,, and approxim approximatel ately y sp 2 hybridised hybridised.. The The nucle nucleop ophil hile e attack attacks s the carbon at 180° to the leaving group, group , since this provides the best overlap between the nucleophile's lone pair and the C-X σ* antibonding orbital. The leaving group is then pushed off the opposite side and the product is formed. If the the subs substr trat ate e unde underr nucl nucleo eoph phil ilic ic atta attack ck is chir chiral al,, this this can can lead lead,, alth althou ough gh not not necessarily, to an inversion of  stereochemistry stereochemistry,, called the Walden inversion. inversion .

SN2 reacti reaction on of bromo bromoet ethan hane e with with hydr hydrox oxide ide ion. ion. The The prod product ucts s are are etha ethanol nol and and a bromide ion. In an example of the S N2 reactio ction, n, the att attack ack of OH of OH− (the (the nucl nucleo eoph phil ile) e) on a bromoethane bromoethane (the electrophile) electrophile) results in ethanol ethanol,, with bromide ejected as the leaving group. SN2

attack

occurs

if

the

backside

route

of

attack

is

not sterically

hindered hindered by substituents substituents on the substrate substrate.. Therefore this mechanism usually occurs at an unhinderedpri unhindered primar mary y car carbon bon centre.

APPLICATIONS

1. Total Synthesis of dl  of dl -Physostigmine -Physostigmine

A concise, highly efficient formal total synthesis of dl  of dl -physostigmine -physostigmine is described, using a relatively simple method that should be adaptable to the synthesis of homologous members of  this type of alkaloid. The key step in the synthesis is a new vicarious nucleophilic substitution  p-nit  N-methylpyrrolidinone.  N-methylpyrrolidinone. reacti reaction on betwee between n  p-n itro roani aniso sole le and and a C-si C-sily lyla late ted d deriv derivat ativ ivee of  Subsequent conversion of the initial adduct to the tricyclic framework of physostigmine follows a well-established protocol and provides the key intermediate 8 in high yield. The vicarious nucleophilic substitution reaction has also been extended to six-membered lactams,

with

encouraging

result.

2. Nucleophilic Substitution Reactions In Ionic Liquids

This paper presents a quantitative comparison of the rates of nucleophilic reactions in ionic liquids and molecular solvents. Both neutral and ionic nucleophiles and electrophiles were used and the solvent effects on these various systems were determined using a Linear Solvation Energy Relationship based on the Kamlet-Taft solvent scales. These correlations reveal that different hydrogen bonding and dipolar interactions provide the dominant effects in determining the rate of reaction, depending upon the specific system under study. The results of this system are useful for predicting nucleophilic interactions at metal centres involved in catalytic  processes.

FUTURE PROSPECTIVE

MICROWAVE ASSISTED SYNTHESIS SYNTHESIS OF AZIDES,THIOCYANATES AZIDES,THIOCYANATES AND SULFONES SULFONES IN AN AQUEOUS MEDIUM

A practical, rapid, and efficient microwave (MW) promoted synthesis of various azides, thiocyanates, and sulfones is described in an aqueous medium. This general and expeditious MW-enhanced nucleophilic substitution approach uses easily accessible starting materials such as halides or tosylates in reaction with alkali azides, thiocyanates, or sulfinates in the absence of any phase-transfer catalyst, and a variety of reactive functional groups are tolerated.

BIBLOGRAPHY 

1.

http://en.wikipedia.org/wiki/SN1_reaction

2. http://en.wikipedia.org/wiki/Substitution_reaction 3. http://en.wikipedia.org/wiki/Substitution_reaction# Electrophilic_substit utions

4. http://en.wikipedia.org/wiki/Substitution_reaction#Radical_substitution s

5. http://pubs.acs.org/doi/abs/10.1021/jo061114h 6. dinkneshethiopiatour.com/0s178w3Dr/  7. R CHANG CHEMISTRY  8. PRADEEP CHEMISTRY  9. DINESH CHEMISTRY