Chapter 12 Reactions of Arenes: Electrophilic Aromatic Substitution

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Chapter 12Reactions of ArenesElectrophilic
Aromatic Substitution
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12.1Representative Electrophilic Aromatic
Substitution Reactions of Benzene
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Electrophilic aromatic substitutions include

• Nitration
• Sulfonation
• Halogenation
• Friedel-Crafts Alkylation
• Friedel-Crafts Acylation

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Table 12.1 Nitration of Benzene
H2SO4

HONO2

H2O
Nitrobenzene(95)
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Table 12.1 Sulfonation of Benzene
heat

HOSO2OH

H2O
Benzenesulfonic acid(100)
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Table 12.1 Halogenation of Benzene
FeBr3

Br2

HBr
Bromobenzene(65-75)
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Table 12.1 Friedel-Crafts Alkylation of Benzene
AlCl3

(CH3)3CCl

HCl
tert-Butylbenzene(60)
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Table 12.1 Friedel-Crafts Acylation of Benzene
AlCl3


HCl
1-Phenyl-1-propanone(88)
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12.2Mechanistic PrinciplesofElectrophilic
Aromatic Substitution
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Step 1 attack of electrophileon p-electron
system of aromatic ring

• highly endothermic
• carbocation is allylic, but not aromatic

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Step 2 loss of a proton from the
carbocationintermediate
H
H
E
H
H
H
H
E

H
H
H
H
H
H

• highly exothermic
• this step restores aromaticity of ring

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Based on this general mechanism

• what remains is to identify the electrophile in
  nitration, sulfonation, halogenation,
  Friedel-Crafts alkylation, and Friedel-Crafts
  acylation to establish the mechanism of specific
  electrophilic aromatic substitutions

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12.3Nitration of Benzene
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Nitration of Benzene
H2SO4

HONO2

H2O
Electrophile isnitronium ion
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Step 1 attack of nitronium cationon p-electron
system of aromatic ring
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Step 2 loss of a proton from the
carbocationintermediate
H
H
NO2
H
H
H
H
NO2

H
H
H
H
H
H
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Where does nitronium ion come from?
H2SO4

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12.4Sulfonation of Benzene
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Sulfonation of Benzene
heat

HOSO2OH

H2O
Several electrophiles present a major one is
sulfur trioxide
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Step 1 attack of sulfur trioxideon p-electron
system of aromatic ring
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Step 2 loss of a proton from the
carbocationintermediate
H
H
SO3
H
H
H
H
SO3

H
H
H
H
H
H
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Step 3 protonation of benzenesulfonate ion
H2SO4
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12.5Halogenation of Benzene
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Halogenation of Benzene
FeBr3

Br2

HBr
Electrophile is a Lewis acid-Lewis basecomplex
between FeBr3 and Br2.
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The Br2-FeBr3 Complex

FeBr3
Lewis base
Lewis acid
Complex

• The Br2-FeBr3 complex is more electrophilic than
  Br2 alone.

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Step 1 attack of Br2-FeBr3 complex on
p-electron system of aromatic ring



Br
Br
FeBr3
H
H
H
H
H
H
FeBr4
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Step 2 loss of a proton from the
carbocationintermediate
H
H
Br
H
H
H
H
Br

H
H
H
H
H
H
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12.6Friedel-Crafts Alkylation of Benzene
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Friedel-Crafts Alkylation of Benzene
AlCl3

(CH3)3CCl

HCl
Electrophile is tert-butyl cation
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Role of AlCl3

• acts as a Lewis acid to promote ionizationof the
  alkyl halide

(CH3)3C
Cl
AlCl3

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Role of AlCl3

• acts as a Lewis acid to promote ionizationof the
  alkyl halide

(CH3)3C
Cl
AlCl3



(CH3)3C
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Step 1 attack of tert-butyl cationon
p-electron system of aromatic ring
H
H
H
H
H
H
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Step 2 loss of a proton from the
carbocationintermediate
H
H
C(CH3)3
H
H
H
H
C(CH3)3

H
H
H
H
H
H
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Rearrangements in Friedel-Crafts Alkylation

• Carbocations are intermediates.
• Therefore, rearrangements can occur

(CH3)2CHCH2Cl
Isobutyl chloride
tert-Butylbenzene(66)
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Rearrangements in Friedel-Crafts Alkylation

• Isobutyl chloride is the alkyl halide.
• But tert-butyl cation is the electrophile.

(CH3)2CHCH2Cl
Isobutyl chloride
tert-Butylbenzene(66)
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Rearrangements in Friedel-Crafts Alkylation


H


H3C
C
CH2
CH3
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Reactions Related to Friedel-Crafts Alkylation
H2SO4

Cyclohexylbenzene(65-68)

• Cyclohexene is protonated by sulfuric acid,
  giving cyclohexyl cation which attacks the
  benzene ring

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12.7Friedel-Crafts Acylation of Benzene
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Friedel-Crafts Acylation of Benzene
O
O
CCH2CH3
AlCl3

CH3CH2CCl

HCl
Electrophile is an acyl cation
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Step 1 attack of the acyl cationon p-electron
system of aromatic ring
H
H
H
H
H
H
H

H
H
H
H
H
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Step 2 loss of a proton from the
carbocationintermediate
H
H
H
H
H
H

H
H
H
H
H
H
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Acid Anhydrides

• can be used instead of acyl chlorides

AlCl3

Acetophenone(76-83)
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12.8Acylation-Reduction
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Acylation-Reduction
permits primary alkyl groups to be attachedto an
aromatic ring
RCCl
AlCl3
Zn(Hg), HCl
CH2R

• Reduction of aldehyde and ketonecarbonyl groups
  using Zn(Hg) and HCl is called the Clemmensen
  reduction.

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Acylation-Reduction
permits primary alkyl groups to be attachedto an
aromatic ring
RCCl
H2NNH2, KOH,triethylene glycol,heat
AlCl3

• Reduction of aldehyde and ketonecarbonyl groups
  by heating with H2NNH2 and KOH is called
  theWolff-Kishner reduction.

CH2R
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Example Prepare isobutylbenzene
(CH3)2CHCH2Cl
CH2CH(CH3)3
AlCl3

• No! Friedel-Crafts alkylation of benzene using
  isobutyl chloride fails because of rearrangement.

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Recall

(CH3)2CHCH2Cl
Isobutyl chloride
tert-Butylbenzene(66)
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Use Acylation-Reduction Instead

AlCl3
Zn(Hg)HCl