aromatic electrophilic substitution paper- c7t

COMPILED AND CIRCULATED BY DR. SK MOHAMMAD AZIZ,

ASSISTANT PROFESSOR, DEPARTMENT OF CHEMISTRY, NARAJOLE RAJ COLLEGE

CHEMISTRY: SEM-III, PAPER- C7T: AROMATIC ELECTROPHILIC SUBSTITUTION

Aromatic Electrophilic

Substitution

Paper- C7T

Narajole Raj College

Department of Chemistry




Introduction:

The most characteristic reaction of benzene and many of its derivatives is

electrophilic aromatic substitution. In an electrophilic aromatic substitution

reaction, a hydrogen of an aromatic ring is substituted by an electrophile—that

is, by a Lewis acid. The general pattern of an electrophilic aromatic substitution

reaction is as follows, where E is the electrophile:

1.1

All electrophilic aromatic substitution reactions occur by similar mechanisms.

This section surveys some of the most common electrophilic aromatic

substitution reactions and their mechanisms.

A. Halogenation of Benzene

When benzene reacts with bromine under harsh conditions—liquid bromine, no

solvent, and the Lewis acid FeBr3 as a catalyst—a reaction occurs in which one

bromine is substituted for a ring hydrogen.

1.2

(Because iron reacts with Br2 to give FeBr3, iron filings can be used in place of

FeBr3.) An analogous chlorination reaction using Cl2 and FeCl3 gives

chlorobenzene. This reaction of benzene with halogens differs from the reaction

of alkenes with halogens in two important ways. First is the type of product




obtained. Alkenes react spontaneously with bromine and chlorine, even in dilute

solution, to give addition products.

1.3

Halogenation of benzene, however, is a substitution reaction; a ring hydrogen is

replaced by a halogen. Second, the reaction conditions for benzene halogenation

are much more severe than the conditions for addition of halogens to an alkene.

The first step in the mechanism of benzene bromination is the formation

of a complex between Br2 and the Lewis acid FeBr3 by a Lewis acid–base

association.

1.4

Formation of this complex results in a formal positive charge on one of the

bromines. A positively charged bromine is a better electron acceptor, and thus a

better leaving group, than a bromine in Br2 itself. Another (and equivalent)

explanation of the leaving-group effect is that –FeBr4 is a weaker base than Br–

. (Remember from Sec. 9.4F that weaker bases are better leaving groups.) –

FeBr4 is essentially the product of a Lewis acid–base association reaction of

Br– with FeBr3. Therefore, in –FeBr4, an electron pair on Br– has already been

donated to Fe, and is thus less available to act as a base, than a “naked” electron

pair on Br– itself.




1.5

The fact that a much better leaving group than ¬Br is required for electrophilic

aromatic substitution illustrates how unreactive the benzene ring is.

1.6

This carbocation is an example of an arenium ion: a carbocation that is formed

by the reaction of an electrophile with a double bond of an aromatic ring.

Although the arenium ion is resonance-stabilized, it is not aromatic. Its

formation disrupts the aromatic stability of the benzene ring. For that reason,

harsh conditions (high temperature and a strong Lewis acid catalyst) are

required for this reaction to proceed at a useful rate. These conditions are much

harsher than those required for bromine addition to an ordinary alkene double




bond (that is, bromine dissolved in an inert solvent, no catalyst, room

temperature or low temperature).

The reaction is completed when a bromide ion (complexed to FeBr3) acts

as a base to remove the ring proton from the arenium ion, regenerate the catalyst

FeBr3, and give the products bromobenzene and HBr.

1.7

Recall that loss of a b-proton is one of the characteristic reactions of

carbocations . Another typical reaction of carbocations—reaction of bromide

ion at the electron-deficient carbon itself—doesn’t occur because the resulting

addition product would not be aromatic:

1.8

By losing a b-proton instead (Eq. 16.7), the carbocation can form

bromobenzene, a stable aromatic compound.

B. The Mechanistic Steps of Electrophilic Aromatic Substitution

Halogenation of benzene is one of many electrophilic aromatic substitution

reactions. The bromination of benzene, for example, is an aromatic substitution

because a hydrogen of benzene (the aromatic compound that undergoes

substitution) is replaced by another group (bromine). The reaction is

electrophilic because the substituting group reacts as an electrophile toward the




benzene p electrons. In bromination, the Lewis acid is a bromine in the complex

of bromine and the FeBr3 catalyst (Eq. 1.6). We’ve considered two other types

of substitution reactions: nucleophilic substitution (the SN2 and SN1 reactions,

Secs. 9.4 and 9.6) and free-radical substitution. In a nucleophilic substitution

reaction, the substituting group acts as a nucleophile; and in free-radical

substitution, free-radical intermediates are involved. Electrophilic aromatic

substitution is the most typical reaction of benzene and its derivatives. As you

learn about other electrophilic substitution reactions, it will help you to

understand them if you can identify in each reaction the following three

mechanistic steps:

Step 1. Generation of an electrophile. The electrophile in bromination is the

complex of bromine with FeBr3, formed as shown in Eq. 1.4

Step 2. Nucleophilic reaction of the p electrons of the aromatic ring with the

electrophile to form a resonance-stabilized carbocation intermediate (an

arenium ion).

1.9a

The electrophile approaches the p-electron cloud of the ring above or below the

plane of the molecule. In the arenium-ion intermediate, the carbon at which the




electrophile reacts becomes sp3-hybridized and tetrahedral. This step in the

bromination mechanism is Eq. 1.6

Step 3. Loss of a proton from the carbocation intermediate to form the

substituted aromatic compound. The proton is lost from the carbon at which

substitution occurs. This carbon again becomes part of the aromatic p-electron

system.

1.9b

Nitration of Benzene

Benzene reacts with concentrated nitric acid, usually in the presence of a

sulfuric acid catalyst, to form nitrobenzene. In this reaction, called nitration, the

nitro group, ¬NO2, is introduced into the benzene ring by electrophilic

substitution.




This reaction fits the mechanistic pattern of the electrophilic aromatic

substitution reaction outlined in the previous section: Step 1. Generation of the

electrophile. In nitration, the electrophile is +NO2, the nitronium ion. This ion is

formed by the acid-catalyzed removal of the elements of water from HNO3.

Step 2. Reaction of the benzene p electrons with the electrophile to form a

resonancestabilized carbocation inter mediate (an arenium ion).

Step 3. Loss of a proton from the carbocation to give a new aromatic compound.




Sulfonation of Benzene

Another electrophilic substitution reaction of benzene is its conversion into

benzenesulfonic acid.

This reaction, called sulfonation, occurs by two mechanisms that operate

simultaneously. Both mechanisms involve sulfur trioxide, a fuming liquid that

reacts violently with water to give H2SO4. The source of SO3 for sulfonation is

usually a solution of SO3 in concentrated H2SO4 called fuming sulfuric acid or

oleum. This material is one of the most acidic Brønsted acids available

commercially.

In one sulfonation mechanism, the electrophile is neutral sulfur trioxide. When

sulfur trioxide reacts with the benzene ring p electrons, an oxygen accepts the

electron pair displaced from sulfur.




1.13

Friedel–Crafts Alkylation of Benzene

The reaction of an alkyl halide with benzene in the presence of a Lewis acid

catalyst gives an alkylbenzene.

This reaction is an example of a Friedel–Crafts alkylation. Recall that an

alkylation is a reaction that results in the transfer of an alkyl group. In a Friedel–

Crafts alkylation, an alkyl group is transferred to an aromatic ring in the

presence of an acid catalyst. In the preceding example, the alkyl group comes

from an alkyl halide and the catalyst is the Lewis acid aluminum trichloride,

AlCl3.

The electrophile in a Friedel–Crafts alkylation is formed by the

complexation of the Lewis acid AlCl3 with the halogen of an alkyl halide in

much the same way that the electrophile in the bromination of benzene is




formed by the complexation of FeBr3 with Br2. If the alkyl halide is secondary

or tertiary, this complex can further react to form carbocation intermediates.

Either the alkyl halide–Lewis acid complex, or the carbocation derived from it,

can serve as the electrophile in a Friedel–Crafts alkylation.

Compare the role of AlCl3 in enhancing the effectiveness of the chloride

leaving group with the similar role of FeBr3 in the bromination of benzene (Eq.

1.5, p. 800) or FeCl3 in the chlorination of benzene:




The reaction of a carbocation with the benzene p electrons is an example of

reaction 1.

Loss of a b-proton to chloride ion completes the alkylation.

Because some carbocations can rearrange, it is not surprising that

rearrangements of alkyl groups are observed in some Friedel–Crafts alkylations

In this example, the alkyl group in the sec-butylbenzene product has rearranged.

Because primary carbocations are too unstable to be involved as intermediates,

it is probably the complex of the alkyl halide and AlCl3 that rearranges. This

complex has enough carbocation character that it behaves like a carbocation.

As we might expect, rearrangement in the Friedel–Crafts alkylation is not

observed if the carbocation intermediate is not prone to rearrangement.




In this example, the alkylating cation is the tert-butyl cation; because it is

tertiary, this carbocation does not rearrange. Alkylbenzenes, such as

butylbenzene that are derived from rearrangementprone alkyl halides, are

generally not prepared by the Friedel–Crafts alkylation, but rather by other

methods. Another complication in Friedel–Crafts alkylation is that the

alkylbenzene products are more reactive than benzene itself This means that the

product can undergo further alkylation, and mixtures of products alkylated to

different extents are observed along with unreacted benzene.

The Friedel-Crafts Acylation

In the presence of aluminum chloride, an acyl chloride reacts with benzene to

give acyl benzene (Scheme 7). The Friedel-Crafts acylation is analogous to the

Friedel-Crafts alkylation, except that the reagent is acyl chloride instead of an

alkyl halide and the product is acyl benzene instead of alkyl benzene.




In the first step a resonance-stabilized acylium ion formed which reacts with

benzene via an electrophilic aromatic substitution reaction to form an acyl

benzene. The carbonyl group in the product has nonbonding electrons that can

form a complex with the Lewis acid (AlCl3). Addition of water hydrolyzes this

complex, giving the free acyl benzene (Scheme 8). Friedel-Crafts reactions do

not occur on strongly deactivated rings, so the acylation stops after one

substitution.

Friedel-Crafts acylations can also be carried out using carboxylic acid

anhydrides. For example, benzene reacts with acetic anhydride in the presence

of Lewis acid to give acetophenone (Scheme 9). Excess of benzene is used in

this reaction to get good yield.




Electrophilic Substitution Reactions with Substituted Benzenes

Substituted benzenes undergo the electrophilic aromatic substitution reactions

such as halogenation, nitration, sulfonation, alkylation and acylation. Some

substituents make the ring more reactive and some make it less reactive than

benzene toward electrophilic aromatic substitution. The rate determining step of

an electrophilic aromatic substitution reaction is the formation of a carbocation

intermediate. So substituents that are capable of donating electrons into the

benzene ring can stabilize the carbocation intermediate, thereby increasing the

rate of electrophilic aromatic substitution.

• In contrast, substituents that withdraw electrons from the benzene ring will

destabilize the carbocation intermediate, thereby decreasing the rate of

electrophilic aromatic substitution. The relative rates of electrophilic aromatic

substitution reaction of benzene and substituted benzenes are given below.

Substituents can donate electrons into a benzene ring or can withdraw from

benzene ring either by inductive effect or resonance effect. Alkyl substituents

that are bonded to a benzene ring can donate electrons inductively. Donation of

electrons through a σ-bond is called inductive electron donation. Withdrawal of

electrons through a σ-bond is called inductive electron withdrawal. For example

methyl group is an electron donating group because of hyperconjugation and

NH3+ group is an electron withdrawing group because it is more




electronegative than a hydrogen. The relative rates of electrophilic substitution

decrease in the following order.

Substituents such as OH, OR and Cl have a lone pair on the atom that is directly

attached to the benzene ring. This lone pair can be delocalized into the ring.

These substituents also withdraw electrons inductively because the atom

attached to the benzene ring is more electronegative than a hydrogen. But

electron donation into the ring by resonance is more significant than inductive

electron withdrawal from the ring.

Substituents such as C=O, C≡N and NO2 withdraw electrons by resonance.

These substituents also withdraw electrons inductively because the atom

attached to the benzene ring is more electronegative than a hydrogen.




• Substituents that make the benzene ring more reactive toward electrophilic

substitution, by donating electrons into the benzene ring, are called the

activating groups. In contrast, substituents that make the benzene ring less

reactive toward electrophilic substitution, by withdrawing electrons from the

benzene ring, are called the deactivating groups.

• Strongly activating substituents such as -NH2, -NHR, -NR2 -OR, and –OH

make the benzene ring more reactive toward electrophilic substitution. The

moderately activating substituents such as –NHCOR and –OCOR, also donate

electrons into the ring by resonance less effectively than that of strongly

activating substituents. Alkyl, aryl, and -CH=CHR groups are weakly activating

substituents.

• Strongly deactivating substituents such as -C≡N, -SO3H, -NO2, and

ammonium ions make the benzene ring less reactive toward electrophilic

substitution. Carbonyl compounds are moderately deactivating substituents and

the halogens are weakly deactivating substituents.

• Substituted benzene undergoes an electrophilic substitution reaction to give an

ortho-isomer, a meta-isomer, a para-isomer or mixture of these isomers. The

substituent already attached to the benzene ring determines the location of the

new substituent.

• All activating substituents and weakly deactivating halogens are ortho-para

directors, and all substituents that are more deactivating are meta directors.




When substituted benzene undergoes an electrophilic substitution reaction, an

ortho-substituted carbocation, a meta-substituted carbocation, and a para-

substituted carbocation can be formed. The relative stabilities of the three

carbocations determine the preferred pathway of the reaction.

• The methoxy substituent (an activating group), for example, donates electron

into the ring and stabilize the ortho- and para-substituted carbocations as

shown. Therefore, the most stable carbocation is obtained by directing the

incoming group to the ortho and para positions. Thus, any substituent that

donates electrons is an ortho-para director.

• In contrast, the ammonuium ion substituent (a deactivating group), for

example, withdraws electron from the ring and destabilize the ortho- and para-

substituted carbocations as shown. Therefore, the most stable carbocation is

obtained by directing the incoming group to the meta position. Thus, any

substituent that withdraws electrons is a meta director.




• In the following examples, the methoxy group and ethyl group are activating

substituents which preferably direct the incoming electrophile to ortho and para

position. These substituted benzenes undergo electrophilic aromatic substitution

faster than benzene.




• A methoxy group is so strongly activating group so that anisole quickly

brominates in water without a catalyst. In the presence of excess bromine, this

reaction proceeds to give the tribromide substituted product.

Electrophilic Substitution Reactions of Substituted Benzenes:

Halogens are deactivating groups, yet they are ortho, para-directors because the

halogens are strongly electronegative, withdrawing electron density from a

carbon atom through the σ-bond, and the halogens have nonbonding electrons

that can donate electron density through π-bonding. If an electrophile reacts at

the ortho or para position, the positive charge of the sigma complex is shared

by the carbon atom bearing the halogen. The nonbonding electrons of the

halogen can further delocalize the charge onto the halogen, giving a halonium

ion structure. This resonance stabilization allows a halogen to be pi-donating,

even though it is sigma-withdrawing.




• Reaction at the meta position gives a sigma complex whose positive charge is

not delocalized onto the halogen-bearing carbon atom. Therefore, the meta

intermediate is not stabilized by the halonium ion structure. Scheme 1 illustrates

the preference for ortho and para substitution in the nitration of chlorobenzene.

• Ortho-para ratio differs with the size of the substituents. Nitration of toluene

preferably gives ortho as the major product where the activating substituent is

methyl group. Electrophilic substitution reaction of ethyl substituted benzene,

however, gives ortho and para isomers equally. Bulky substituent such as tert-

butyl benzene preferably gives para-isomer as the major product




• Benzenes which are having a meta director (a deactivating group) on the ring,

will be too unreactive to undergo either Friedel-Crafts alkylation or Friedel-

Crafts Acylation

• Aniline and N-substituted anilines also do not undergo Friedel-Crafts reactions

because the lone pair on the amino group will form complex with the Lewis

acid and converting the substituent into a deactivating meta director. Tertiary

aromatic amines, however, can undergo electrophilic substitution because the

tertiary amino group is a strong activator




• Phenols are highly reactive substrates for electrophilic aromatic substitution

because of the presence of a strong activating group. So phenols can be

alkylated or acylated using relatively weak Friedel-Crafts catalysts such as HF

Phenoxide ions, generated by treating a phenol with sodium hydroxide, are even

more reactive than phenols toward electrophilic aromatic substitution. It gives

tribromosubstituted phenol when reacts with excess bromine and salicylic acid

when reacts with carbon dioxide




References:

1. Organic Chemistry, Marc Loudon.

2. NPTEL Biotechnology, Cell Biology

aromatic electrophilic substitution paper- c7t

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