Aromatic Electrophilic Substitution Paper- C7T
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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
COMPILED AND CIRCULATED BY DR. SK MOHAMMAD AZIZ,
ASSISTANT PROFESSOR, DEPARTMENT OF CHEMISTRY, NARAJOLE RAJ COLLEGE
CHEMISTRY: SEM-III, PAPER- C7T: AROMATIC ELECTROPHILIC SUBSTITUTION
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
COMPILED AND CIRCULATED BY DR. SK MOHAMMAD AZIZ,
ASSISTANT PROFESSOR, DEPARTMENT OF CHEMISTRY, NARAJOLE RAJ COLLEGE
CHEMISTRY: SEM-III, PAPER- C7T: AROMATIC ELECTROPHILIC SUBSTITUTION
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.
COMPILED AND CIRCULATED BY DR. SK MOHAMMAD AZIZ,
ASSISTANT PROFESSOR, DEPARTMENT OF CHEMISTRY, NARAJOLE RAJ COLLEGE
CHEMISTRY: SEM-III, PAPER- C7T: AROMATIC ELECTROPHILIC SUBSTITUTION
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
COMPILED AND CIRCULATED BY DR. SK MOHAMMAD AZIZ,
ASSISTANT PROFESSOR, DEPARTMENT OF CHEMISTRY, NARAJOLE RAJ COLLEGE
CHEMISTRY: SEM-III, PAPER- C7T: AROMATIC ELECTROPHILIC SUBSTITUTION
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
COMPILED AND CIRCULATED BY DR. SK MOHAMMAD AZIZ,
ASSISTANT PROFESSOR, DEPARTMENT OF CHEMISTRY, NARAJOLE RAJ COLLEGE
CHEMISTRY: SEM-III, PAPER- C7T: AROMATIC ELECTROPHILIC SUBSTITUTION
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
COMPILED AND CIRCULATED BY DR. SK MOHAMMAD AZIZ,
ASSISTANT PROFESSOR, DEPARTMENT OF CHEMISTRY, NARAJOLE RAJ COLLEGE
CHEMISTRY: SEM-III, PAPER- C7T: AROMATIC ELECTROPHILIC SUBSTITUTION
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.
COMPILED AND CIRCULATED BY DR. SK MOHAMMAD AZIZ,
ASSISTANT PROFESSOR, DEPARTMENT OF CHEMISTRY, NARAJOLE RAJ COLLEGE
CHEMISTRY: SEM-III, PAPER- C7T: AROMATIC 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.
COMPILED AND CIRCULATED BY DR. SK MOHAMMAD AZIZ,
ASSISTANT PROFESSOR, DEPARTMENT OF CHEMISTRY, NARAJOLE RAJ COLLEGE
CHEMISTRY: SEM-III, PAPER- C7T: AROMATIC ELECTROPHILIC SUBSTITUTION
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.
COMPILED AND CIRCULATED BY DR. SK MOHAMMAD AZIZ,
ASSISTANT PROFESSOR, DEPARTMENT OF CHEMISTRY, NARAJOLE RAJ COLLEGE
CHEMISTRY: SEM-III, PAPER- C7T: AROMATIC ELECTROPHILIC SUBSTITUTION
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
COMPILED AND CIRCULATED BY DR. SK MOHAMMAD AZIZ,
ASSISTANT PROFESSOR, DEPARTMENT OF CHEMISTRY, NARAJOLE RAJ COLLEGE
CHEMISTRY: SEM-III, PAPER- C7T: AROMATIC ELECTROPHILIC SUBSTITUTION
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:
COMPILED AND CIRCULATED BY DR. SK MOHAMMAD AZIZ,
ASSISTANT PROFESSOR, DEPARTMENT OF CHEMISTRY, NARAJOLE RAJ COLLEGE
CHEMISTRY: SEM-III, PAPER- C7T: AROMATIC ELECTROPHILIC SUBSTITUTION
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.
COMPILED AND CIRCULATED BY DR. SK MOHAMMAD AZIZ,
ASSISTANT PROFESSOR, DEPARTMENT OF CHEMISTRY, NARAJOLE RAJ COLLEGE
CHEMISTRY: SEM-III, PAPER- C7T: AROMATIC ELECTROPHILIC SUBSTITUTION
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.
COMPILED AND CIRCULATED BY DR. SK MOHAMMAD AZIZ,
ASSISTANT PROFESSOR, DEPARTMENT OF CHEMISTRY, NARAJOLE RAJ COLLEGE
CHEMISTRY: SEM-III, PAPER- C7T: AROMATIC ELECTROPHILIC SUBSTITUTION
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.
COMPILED AND CIRCULATED BY DR. SK MOHAMMAD AZIZ,
ASSISTANT PROFESSOR, DEPARTMENT OF CHEMISTRY, NARAJOLE RAJ COLLEGE
CHEMISTRY: SEM-III, PAPER- C7T: AROMATIC ELECTROPHILIC SUBSTITUTION
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
COMPILED AND CIRCULATED BY DR. SK MOHAMMAD AZIZ,
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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.
COMPILED AND CIRCULATED BY DR. SK MOHAMMAD AZIZ,
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• 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.
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ASSISTANT PROFESSOR, DEPARTMENT OF CHEMISTRY, NARAJOLE RAJ COLLEGE
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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.
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• 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.
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• 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.
COMPILED AND CIRCULATED BY DR. SK MOHAMMAD AZIZ,
ASSISTANT PROFESSOR, DEPARTMENT OF CHEMISTRY, NARAJOLE RAJ COLLEGE
CHEMISTRY: SEM-III, PAPER- C7T: AROMATIC ELECTROPHILIC SUBSTITUTION
• 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
COMPILED AND CIRCULATED BY DR. SK MOHAMMAD AZIZ,
ASSISTANT PROFESSOR, DEPARTMENT OF CHEMISTRY, NARAJOLE RAJ COLLEGE
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• 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
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• 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
COMPILED AND CIRCULATED BY DR. SK MOHAMMAD AZIZ,
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References:
1. Organic Chemistry, Marc Loudon.
2. NPTEL Biotechnology, Cell Biology
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