Transcript Organic Chemistry Fifth Edition

Chapter 12
Reactions of Arenes:
Electrophilic Aromatic Substitution
H
+
+E
–
Y
E
+H
Y
12.1
Representative Electrophilic Aromatic
Substitution Reactions of Benzene
H
+
+E
–
Y
E
+H
Y
H
+
+E
–
E
Y
+H
Electrophilic aromatic substitutions include:
Nitration
Sulfonation
Halogenation
Friedel-Crafts Alkylation
Friedel-Crafts Acylation
Y
Table 12.1: Nitration of Benzene
H
+ HONO2
H2SO4
NO2
+ H2O
Nitrobenzene
(95%)
Table 12.1: Sulfonation of Benzene
H
heat
+ HOSO2OH
SO2OH
+ H2O
Benzenesulfonic acid
(100%)
Table 12.1: Halogenation of Benzene
H
+ Br2
FeBr3
Br
+ HBr
Bromobenzene
(65-75%)
Table 12.1: Friedel-Crafts Alkylation of Benzene
H
+ (CH3)3CCl
AlCl3
C(CH3)3
+ HCl
tert-Butylbenzene
(60%)
Table 12.1: Friedel-Crafts Acylation of Benzene
O
O
H
AlCl3
+ CH3CH2CCl
CCH2CH3
+ HCl
1-Phenyl-1-propanone
(88%)
12.2
Mechanistic Principles
of
Electrophilic Aromatic Substitution
Step 1: attack of electrophile
on -electron system of aromatic ring
E+
H
H
H
H
H
H E
H
H
H
+
H
highly endothermic
carbocation is allylic, but not aromatic
H
H
Step 2: loss of a proton from the carbocation
intermediate
H
H
H
E
H
H
H E
H
H
H+
+
H
highly exothermic
this step restores aromaticity of ring
H
H
H E
H
H
+
H
H
H
H
H + E+
H
H
H
H
H
H
E + H+
H
H
H
Based on this general mechanism:
what remains is to identify the electrophile in
nitration, sulfonation, halogenation, FriedelCrafts alkylation, and Friedel-Crafts acylation
to establish the mechanism of specific
electrophilic aromatic substitutions
12.3
Nitration of Benzene
Nitration of Benzene
H
+ HONO2
Electrophile is
nitronium ion
NO2
H2SO4
+ H2O
•• O
••
+
N
O ••
••
Step 1: attack of nitronium cation
on -electron system of aromatic ring
H
H
H
NO2+
H
H
H
H NO2
H
H
+
H
H
H
Step 2: loss of a proton from the carbocation
intermediate
H
H
NO2
H
H
H NO2
H
H
H+
H
+
H
H
H
Where does nitronium ion come from?
••
•• O
+
N
•• O
••
•• –
O ••
••
•• –
O ••
••
••
•• O
H2SO4
+
N
+O
••
H
H
•• O
••
+
N
H
••
O ••
••
+
O
H
••
H
12.4
Sulfonation of Benzene
Sulfonation of Benzene
H
heat
+ HOSO2OH
SO2OH
+ H2O
••
Several electrophiles present:
a major one is sulfur trioxide
•• O
+
S
•• O
••
•• –
O ••
••
Step 1: attack of sulfur trioxide
on -electron system of aromatic ring
H
H
H
SO3
H
H
H
H SO3–
H
H
+
H
H
H
Step 2: loss of a proton from the carbocation
intermediate
H
H
SO3–
H
H
H
H SO3–
H
H+
H
+
H
H
H
Step 3: protonation of benzenesulfonate ion
H
H
SO3–
H
H
H
H2SO4
H
H
H
SO3H
H
H
12.5
Halogenation of Benzene
Halogenation of Benzene
H
+ Br2
FeBr3
Electrophile is a Lewis acid-Lewis base
complex between FeBr3 and Br2.
Br
+ HBr
The Br2-FeBr3 Complex
••
•• Br
••
••
Br ••
••
Lewis base
+ FeBr3
Lewis acid
••
•• Br
••
+
••
Br
••
–
FeBr3
Complex
The Br2-FeBr3 complex is more electrophilic
than Br2 alone.
Step 1: attack of Br2-FeBr3 complex
on -electron system of aromatic ring
H
H
H
Br
H
H
H
+
Br
–
FeBr3
H Br
H
H
+
H
H
H
+ FeBr4–
Step 2: loss of a proton from the carbocation
intermediate
H
H
Br
H
H
H Br
H
H
H+
H
+
H
H
H
12.6
Friedel-Crafts Alkylation of Benzene
Friedel-Crafts Alkylation of Benzene
H
+ (CH3)3CCl
C(CH3)3
AlCl3
+ HCl
H3C
Electrophile is
tert-butyl cation
H3C
+
C
CH3
Role of AlCl3
acts as a Lewis acid to promote ionization
of the alkyl halide
(CH3)3C
••
Cl ••
••
+
AlCl3
(CH3)3C
+
••
(CH3)3C + •• Cl
••
–
AlCl3
+
••
Cl
••
–
AlCl3
Step 1: attack of tert-butyl cation
on -electron system of aromatic ring
H
H
H
+
C(CH3)3
H
H
H
H C(CH3)3
H
H
+
H
H
H
Step 2: loss of a proton from the carbocation
intermediate
H
H
C(CH3)3
H
H
H C(CH3)3
H
H
H+
H
+
H
H
H
Rearrangements in Friedel-Crafts Alkylation
Carbocations are intermediates.
Therefore, rearrangements can occur
H
+ (CH3)2CHCH2Cl
Isobutyl chloride
AlCl3
C(CH3)3
tert-Butylbenzene
(66%)
Rearrangements in Friedel-Crafts Alkylation
Isobutyl chloride is the alkyl halide.
But tert-butyl cation is the
electrophile.
H
+ (CH3)2CHCH2Cl
Isobutyl chloride
AlCl3
C(CH3)3
tert-Butylbenzene
(66%)
Rearrangements in Friedel-Crafts Alkylation
H
H3C
C
CH2
+
••
Cl
••
–
AlCl3
CH3
H
H3C
+
C
CH3
CH2
+
••
•• Cl
••
–
AlCl3
Reactions Related to Friedel-Crafts Alkylation
H
+
H2SO4
Cyclohexylbenzene
(65-68%)
Cyclohexene is protonated by sulfuric acid,
giving cyclohexyl cation which attacks the
benzene ring
12.7
Friedel-Crafts Acylation of Benzene
Friedel-Crafts Acylation of Benzene
O
O
H
AlCl3
+ CH3CH2CCl
CCH2CH3
+ HCl
Electrophile is an acyl cation
+
CH3CH2C
••
O ••
CH3CH2C
+
O ••
Step 1: attack of the acyl cation
on -electron system of aromatic ring
O
H
H
H
CCH2CH3
H +
H
H
O
H
H
H CCH2CH3
+
H
H
H
Step 2: loss of a proton from the carbocation
intermediate
O
H
H
O
CCH2CH3
H
H
H
H CCH2CH3
H
H+
H
+
H
H
H
Acid Anhydrides
can be used instead of acyl chlorides
O
H
O O
AlCl3
CCH3
+ CH3COCCH3
Acetophenone
(76-83%)
O
+ CH3COH
12.8
Acylation-Reduction
Acylation-Reduction
permits primary alkyl groups to be attached
to an aromatic ring
O
H
RCCl
O
CR
AlCl3
Reduction of aldehyde and ketone
carbonyl groups using Zn(Hg) and HCl is
called the Clemmensen reduction.
Zn(Hg), HCl
CH2R
Acylation-Reduction
permits primary alkyl groups to be attached
to an aromatic ring
O
H
RCCl
O
CR
AlCl3
Reduction of aldehyde and ketone
carbonyl groups by heating with H2NNH2
and KOH is called the
Wolff-Kishner reduction.
H2NNH2, KOH,
triethylene glycol,
heat
CH2R
Example: Prepare isobutylbenzene
H
(CH3)2CHCH2Cl
CH2CH(CH3)3
AlCl3
No! Friedel-Crafts alkylation of benzene
using isobutyl chloride fails because of
rearrangement.
Recall
H
+ (CH3)2CHCH2Cl
Isobutyl chloride
AlCl3
C(CH3)3
tert-Butylbenzene
(66%)
Use Acylation-Reduction Instead
O
H
+ (CH3)2CHCCl
AlCl3
Zn(Hg)
HCl
O
CCH(CH3)2
CH2CH(CH3)3