Title: Chapter 12 Reactions of Arenes: Electrophilic Aromatic Substitution
1Chapter 12Reactions of ArenesElectrophilic
Aromatic Substitution
212.1Representative Electrophilic Aromatic
Substitution Reactions of Benzene
3Electrophilic aromatic substitutions include
- Nitration
- Sulfonation
- Halogenation
- Friedel-Crafts Alkylation
- Friedel-Crafts Acylation
4Table 12.1 Nitration of Benzene
H2SO4
HONO2
H2O
Nitrobenzene(95)
5Table 12.1 Sulfonation of Benzene
heat
HOSO2OH
H2O
Benzenesulfonic acid(100)
6Table 12.1 Halogenation of Benzene
FeBr3
Br2
HBr
Bromobenzene(65-75)
7Table 12.1 Friedel-Crafts Alkylation of Benzene
AlCl3
(CH3)3CCl
HCl
tert-Butylbenzene(60)
8Table 12.1 Friedel-Crafts Acylation of Benzene
AlCl3
HCl
1-Phenyl-1-propanone(88)
912.2Mechanistic PrinciplesofElectrophilic
Aromatic Substitution
10Step 1 attack of electrophileon ?-electron
system of aromatic ring
- highly endothermic
- carbocation is allylic, but not aromatic
11Step 2 loss of a proton from the
carbocationintermediate
H
H
E
H
H
H
H
- highly exothermic
- this step restores aromaticity of ring
12(No Transcript)
13Based 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
1412.3Nitration of Benzene
15Nitration of Benzene
H2SO4
HONO2
H2O
16Step 1 attack of nitronium cationon ?-electron
system of aromatic ring
17Step 2 loss of a proton from the
carbocationintermediate
H
H
NO2
H
H
H
H
18Where does nitronium ion come from?
H2SO4
1912.4Sulfonation of Benzene
20Sulfonation of Benzene
heat
HOSO2OH
H2O
21Step 1 attack of sulfur trioxideon ?-electron
system of aromatic ring
22Step 2 loss of a proton from the
carbocationintermediate
H
H
SO3
H
H
H
H
23Step 3 protonation of benzenesulfonate ion
H2SO4
2412.5Halogenation of Benzene
25Halogenation of Benzene
FeBr3
Br2
HBr
Electrophile is a Lewis acid-Lewis basecomplex
between FeBr3 and Br2.
26The Br2-FeBr3 Complex
FeBr3
Lewis base
Lewis acid
- The Br2-FeBr3 complex is more electrophilic than
Br2 alone.
27Step 1 attack of Br2-FeBr3 complex on
?-electron system of aromatic ring
Br
Br
FeBr3
H
H
H
H
H
H
28Step 2 loss of a proton from the
carbocationintermediate
H
H
Br
H
H
H
H
2912.6Friedel-Crafts Alkylation of Benzene
30Friedel-Crafts Alkylation of Benzene
AlCl3
(CH3)3CCl
HCl
31Role of AlCl3
- acts as a Lewis acid to promote ionizationof the
alkyl halide
(CH3)3C
Cl
AlCl3
32Step 1 attack of tert-butyl cationon
?-electron system of aromatic ring
H
H
H
H
H
H
33Step 2 loss of a proton from the
carbocationintermediate
H
H
C(CH3)3
H
H
H
H
34Rearrangements in Friedel-Crafts Alkylation
- Carbocations are intermediates.
- Therefore, rearrangements can occur
35Rearrangements in Friedel-Crafts Alkylation
- Isobutyl chloride is the alkyl halide.
- But tert-butyl cation is the electrophile.
(CH3)2CHCH2Cl
Isobutyl chloride
tert-Butylbenzene(66)
36Rearrangements in Friedel-Crafts Alkylation
37Reactions Related to Friedel-Crafts Alkylation
H2SO4
Cyclohexylbenzene(65-68)
- Cyclohexene is protonated by sulfuric acid,
giving cyclohexyl cation which attacks the
benzene ring
3812.7Friedel-Crafts Acylation of Benzene
39Friedel-Crafts Acylation of Benzene
O
O
CCH2CH3
AlCl3
CH3CH2CCl
HCl
40Step 1 attack of the acyl cationon ?-electron
system of aromatic ring
H
H
H
H
H
H
41Step 2 loss of a proton from the
carbocationintermediate
42Acid Anhydrides
- can be used instead of acyl chlorides
AlCl3
Acetophenone(76-83)
4312.8Acylation-Reduction
44Acylation-Reduction
permits primary alkyl groups to be attachedto an
aromatic ring
RCCl
AlCl3
- Reduction of aldehyde and ketonecarbonyl groups
using Zn(Hg) and HCl is called the Clemmensen
reduction.
45Acylation-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
46Example Prepare isobutylbenzene
(CH3)2CHCH2Cl
CH2CH(CH3)3
AlCl3
- No! Friedel-Crafts alkylation of benzene using
isobutyl chloride fails because of rearrangement.
47Recall
(CH3)2CHCH2Cl
Isobutyl chloride
tert-Butylbenzene(66)
48Use Acylation-Reduction Instead
AlCl3