Chapter 12 (Part a) Reactions of Arenes: Electrophilic Aromatic Substitution

1
Chapter 12 (Part a)Reactions of
ArenesElectrophilic Aromatic Substitution
Dr. Wolf's CHM 201 202
12-1
2
Representative Electrophilic Aromatic
Substitution Reactions of Benzene
Dr. Wolf's CHM 201 202
12-2
3
Electrophilic aromatic substitutions include

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

Dr. Wolf's CHM 201 202
12-3
4
Table 12.1 Nitration of Benzene
H2SO4

HONO2

H2O
Nitrobenzene(95)
Dr. Wolf's CHM 201 202
12-4
5
Table 12.1 Sulfonation of Benzene
heat

HOSO2OH

H2O
Benzenesulfonic acid(100)
Dr. Wolf's CHM 201 202
12-5
6
Table 12.1 Halogenation of Benzene
FeBr3

Br2

HBr
Bromobenzene(65-75)
Dr. Wolf's CHM 201 202
12-6
7
Table 12.1 Friedel-Crafts Alkylation of Benzene
AlCl3

(CH3)3CCl

HCl
tert-Butylbenzene(60)
Dr. Wolf's CHM 201 202
12-7
8
Table 12.1 Friedel-Crafts Acylation of Benzene
AlCl3


HCl
1-Phenyl-1-propanone(88)
Dr. Wolf's CHM 201 202
12-8
9
Mechanistic PrinciplesofElectrophilic Aromatic
Substitution
Dr. Wolf's CHM 201 202
12-9
10
Step 1 attack of electrophileon p-electron
system of aromatic ring

• highly endothermic
• carbocation is allylic, but not aromatic

Dr. Wolf's CHM 201 202
12-10
11
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

Dr. Wolf's CHM 201 202
12-11
12
Dr. Wolf's CHM 201 202
12-12
13
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

Dr. Wolf's CHM 201 202
12-13
14
Nitration of Benzene
Dr. Wolf's CHM 201 202
12-14
15
Nitration of Benzene
H2SO4

HONO2

H2O
Electrophile isnitronium ion
Dr. Wolf's CHM 201 202
12-15
16
Step 1 attack of nitronium cationon p-electron
system of aromatic ring
Dr. Wolf's CHM 201 202
12-16
17
Step 2 loss of a proton from the
carbocationintermediate
H
H
NO2
H
H
H
H
NO2

H
H
H
H
H
H
Dr. Wolf's CHM 201 202
12-17
18
Where does nitronium ion come from?
H2SO4

Dr. Wolf's CHM 201 202
12-18
19
Sulfonation of Benzene
Dr. Wolf's CHM 201 202
12-19
20
Sulfonation of Benzene
heat

HOSO2OH

H2O
Several electrophiles present a major one is
sulfur trioxide
Dr. Wolf's CHM 201 202
12-20
21
Step 1 attack of sulfur trioxideon p-electron
system of aromatic ring
Dr. Wolf's CHM 201 202
12-21
22
Step 2 loss of a proton from the
carbocationintermediate
H
H
SO3
H
H
H
H
SO3

H
H
H
H
H
H
Dr. Wolf's CHM 201 202
12-22
23
Step 3 protonation of benzenesulfonate ion
H2SO4
Dr. Wolf's CHM 201 202
12-23
24
Halogenation of Benzene
Dr. Wolf's CHM 201 202
12-24
25
Halogenation of Benzene
FeBr3

Br2

HBr
Electrophile is a Lewis acid-Lewis basecomplex
between FeBr3 and Br2.
Dr. Wolf's CHM 201 202
12-25
26
The Br2-FeBr3 Complex

FeBr3
Lewis base
Lewis acid
Complex

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

Dr. Wolf's CHM 201 202
12-26
27
Step 1 attack of Br2-FeBr3 complex on
p-electron system of aromatic ring



Br
Br
FeBr3
H
H
H
H
H
H
FeBr4
Dr. Wolf's CHM 201 202
12-27
28
Step 2 loss of a proton from the
carbocationintermediate
H
H
Br
H
H
H
H
Br

H
H
H
H
H
H
Dr. Wolf's CHM 201 202
12-28
29
Friedel-Crafts Alkylation of Benzene
Dr. Wolf's CHM 201 202
12-29
30
Friedel-Crafts Alkylation of Benzene
AlCl3

(CH3)3CCl

HCl
Electrophile is tert-butyl cation
Dr. Wolf's CHM 201 202
12-30
31
Role of AlCl3

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

(CH3)3C
Cl
AlCl3

Dr. Wolf's CHM 201 202
12-31
32
Role of AlCl3

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

(CH3)3C
Cl
AlCl3



(CH3)3C
Dr. Wolf's CHM 201 202
12-32
33
Step 1 attack of tert-butyl cationon
p-electron system of aromatic ring
H
H
H
H
H
H
Dr. Wolf's CHM 201 202
12-33
34
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
Dr. Wolf's CHM 201 202
12-34
35
Rearrangements in Friedel-Crafts Alkylation

• Carbocations are intermediates.
• Therefore, rearrangements can occur

(CH3)2CHCH2Cl
Isobutyl chloride
tert-Butylbenzene(66)
Dr. Wolf's CHM 201 202
12-35
36
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)
Dr. Wolf's CHM 201 202
12-36
37
Rearrangements in Friedel-Crafts Alkylation


H


H3C
C
CH2
CH3
Dr. Wolf's CHM 201 202
12-37
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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

Dr. Wolf's CHM 201 202
12-38
39
Friedel-Crafts Acylation of Benzene
Dr. Wolf's CHM 201 202
12-39
40
Friedel-Crafts Acylation of Benzene
O
O
CCH2CH3
AlCl3

CH3CH2CCl

HCl
Electrophile is an acyl cation
Dr. Wolf's CHM 201 202
12-40
41
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
Dr. Wolf's CHM 201 202
12-41
42
Step 2 loss of a proton from the
carbocationintermediate
H
H
H
H
H
H

H
H
H
H
H
H
Dr. Wolf's CHM 201 202
12-42
43
Acid Anhydrides

• can be used instead of acyl chlorides

AlCl3

Acetophenone(76-83)
Dr. Wolf's CHM 201 202
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Acylation-Reduction
Dr. Wolf's CHM 201 202
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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.

Dr. Wolf's CHM 201 202
12-45
46
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
Dr. Wolf's CHM 201 202
12-46
47
Example Prepare isobutylbenzene
(CH3)2CHCH2Cl
CH2CH(CH3)2
AlCl3

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

Dr. Wolf's CHM 201 202
12-47
48
Recall

(CH3)2CHCH2Cl
Isobutyl chloride
tert-Butylbenzene(66)
Dr. Wolf's CHM 201 202
12-48
49
Use Acylation-Reduction Instead

AlCl3
Zn(Hg)HCl
Dr. Wolf's CHM 201 202
12-49
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Rate and Regioselectivity in Electrophilic
Aromatic Substitution

• A substituent already present on the ring can
  affect both the rate and regioselectivityof
  electrophilic aromatic substitution.

Dr. Wolf's CHM 201 202
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Effect on Rate

• Activating substituents increase the rate of
  EAS compared to that of benzene.
• Deactivating substituents decrease the rate of
  EAS compared to benzene.

Dr. Wolf's CHM 201 202
12-51
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Methyl Group

• Toluene undergoes nitration 20-25 times faster
  than benzene.
• A methyl group is an activating substituent.

Dr. Wolf's CHM 201 202
12-52
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Trifluoromethyl Group

• (Trifluoromethyl)benzene undergoes nitration
  40,000 times more slowly than benzene .
• A trifluoromethyl group is adeactivating
  substituent.

Dr. Wolf's CHM 201 202
12-53
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Effect on Regioselectivity

• Ortho-para directors direct an incoming
  electrophile to positions ortho and/or para to
  themselves.
• Meta directors direct an incoming electrophile
  to positions meta to themselves.

Dr. Wolf's CHM 201 202
12-54
55
Nitration of Toluene


34
3
63

• o- and p-nitrotoluene together comprise 97 of
  the product
• a methyl group is an ortho-para director

Dr. Wolf's CHM 201 202
12-55
56
Nitration of (Trifluoromethyl)benzene


3
91
6

• m-nitro(trifluoromethyl)benzene comprises 91 of
  the product
• a trifluoromethyl group is a meta director

Dr. Wolf's CHM 201 202
12-56
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Rate and Regioselectivityin theNitration of
Toluene
Dr. Wolf's CHM 201 202
12-57
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Carbocation Stability Controls Regioselectivity
gives ortho
gives para
gives meta
Dr. Wolf's CHM 201 202
12-58
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Carbocation Stability Controls Regioselectivity
gives ortho
gives para
gives meta
more stable
less stable
Dr. Wolf's CHM 201 202
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ortho Nitration of Toluene
CH3
NO2
H
H
H
H
H
Dr. Wolf's CHM 201 202
12-60
61
ortho Nitration of Toluene
CH3
CH3
NO2
NO2
H
H
H
H

H
H
H
H
H
H
Dr. Wolf's CHM 201 202
12-61
62
ortho Nitration of Toluene
CH3
CH3
CH3
NO2
NO2
NO2
H
H
H

H
H
H

H
H
H
H
H
H
H
H
H

• this resonance form is a tertiary carbocation

Dr. Wolf's CHM 201 202
12-62
63
ortho Nitration of Toluene
CH3
CH3
CH3
NO2
NO2
NO2
H
H
H

H
H
H

H
H
H
H
H
H
H
H
H

• the rate-determining intermediate in the
  orthonitration of toluene has tertiary
  carbocation character

Dr. Wolf's CHM 201 202
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64
para Nitration of Toluene
Dr. Wolf's CHM 201 202
12-64
65
para Nitration of Toluene

• this resonance form is a tertiary carbocation

Dr. Wolf's CHM 201 202
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66
para Nitration of Toluene

• this resonance form is a tertiary carbocation

Dr. Wolf's CHM 201 202
12-66
67
para Nitration of Toluene

• the rate-determining intermediate in the
  paranitration of toluene has tertiary
  carbocation character

Dr. Wolf's CHM 201 202
12-67
68
meta Nitration of Toluene
Dr. Wolf's CHM 201 202
12-68
69
meta Nitration of Toluene

Dr. Wolf's CHM 201 202
12-69
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meta Nitration of Toluene

• all the resonance forms of the rate-determining
  intermediate in the meta nitration of toluene
  have their positive charge on a secondary carbon

Dr. Wolf's CHM 201 202
12-70
71
Nitration of Toluene Interpretation

• The rate-determining intermediates for ortho and
  para nitration each have a resonance form that is
  a tertiary carbocation. All of the resonance
  forms for the rate-determining intermediate in
  meta nitration are secondary carbocations.
• Tertiary carbocations, being more stable, are
  formed faster than secondary ones. Therefore,
  the intermediates for attack at the ortho and
  para positions are formed faster than the
  intermediate for attack at the meta position.
  This explains why the major products are o- and
  p-nitrotoluene.

Dr. Wolf's CHM 201 202
12-71
72
Nitration of Toluene Partial Rate Factors

• The experimentally determined reaction rate can
  be combined with the ortho/meta/para distribution
  to give partial rate factors for substitution at
  the various ring positions.
• Expressed as a numerical value, a partial rate
  factor tells you by how much the rate of
  substitution at a particular position is faster
  (or slower) than at a single position of benzene.

Dr. Wolf's CHM 201 202
12-72
73
Nitration of Toluene Partial Rate Factors
1
42
42
1
1
2.5
2.5
1
1
1
58

• All of the available ring positions in toluene
  are more reactive than a single position of
  benzene.
• A methyl group activates all of the ring
  positions but the effect is greatest at the ortho
  and para positons.
• Steric hindrance by the methyl group makes each
  ortho position slightly less reactive than para.

Dr. Wolf's CHM 201 202
12-73
74
Nitration of Toluene vs. tert-Butylbenzene

• tert-Butyl is activating and ortho-para
  directing
• tert-Butyl crowds the ortho positions and
  decreases the rate of attack at those positions.

Dr. Wolf's CHM 201 202
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75
Generalization

• all alkyl groups are activating and ortho-para
  directing

Dr. Wolf's CHM 201 202
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76
Theory of Directing Effects
77
Rate and Regioselectivityin theNitration of
(Trifluoromethyl)benzene
Dr. Wolf's CHM 201 202
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78
A Key Point

• A methyl group is electron-donating and
  stabilizes a carbocation.
• Because F is so electronegative, a CF3 group
  destabilizes a carbocation.

Dr. Wolf's CHM 201 202
12-77
79
Carbocation Stability Controls Regioselectivity
gives ortho
gives para
gives meta
Dr. Wolf's CHM 201 202
12-78
80
Carbocation Stability Controls Regioselectivity
gives ortho
gives para
gives meta
less stable
more stable
Dr. Wolf's CHM 201 202
12-79
81
ortho Nitration of (Trifluoromethyl)benzene
CF3
NO2
H
H
H
H
H
Dr. Wolf's CHM 201 202
12-80
82
ortho Nitration of (Trifluoromethyl)benzene
CF3
CF3
NO2
NO2
H
H
H
H

H
H
H
H
H
H
Dr. Wolf's CHM 201 202
12-81
83
ortho Nitration of (Trifluoromethyl)benzene
CF3
CF3
CF3
NO2
NO2
NO2
H
H
H

H
H
H

H
H
H
H
H
H
H
H
H

• this resonance form is destabilized

Dr. Wolf's CHM 201 202
12-82
84
ortho Nitration of (Trifluoromethyl)benzene
CF3
CF3
CF3
NO2
NO2
NO2
H
H
H

H
H
H

H
H
H
H
H
H
H
H
H

• one of the resonance forms of the
  rate-determining intermediate in the
  orthonitration of (trifluoromethyl)benzene is
  strongly destabilized

Dr. Wolf's CHM 201 202
12-83
85
para Nitration of (Trifluoromethyl)benzene
Dr. Wolf's CHM 201 202
12-84
86
para Nitration of (Trifluoromethyl)benzene

• this resonance form is destabilized

Dr. Wolf's CHM 201 202
12-85
87
para Nitration of (Trifluoromethyl)benzene

• this resonance form is destabilized

Dr. Wolf's CHM 201 202
12-86
88
para Nitration of (Trifluoromethyl)benzene

• one of the resonance forms of the
  rate-determining intermediate in the
  paranitration of (trifluoromethyl)benzene is
  strongly destabilized

Dr. Wolf's CHM 201 202
12-87
89
meta Nitration of (Trifluoromethyl)benzene
Dr. Wolf's CHM 201 202
12-88
90
meta Nitration of (Trifluoromethyl)benzene

Dr. Wolf's CHM 201 202
12-89
91
meta Nitration of (Trifluoromethyl)benzene

• none of the resonance forms of the
  rate-determining intermediate in the meta
  nitration of (trifluoromethyl)benzene have their
  positive charge on the carbon that bears the CF3
  group

Dr. Wolf's CHM 201 202
12-90
92
Nitration of (Trifluoromethyl)benzene
Interpretation

• The rate-determining intermediates for ortho and
  para nitration each have a resonance form in
  which the positive charge is on a carbon that
  bears a CF3 group. Such a resonance structure is
  strongly destabilized. The intermediate in meta
  nitration avoids such a structure. It is the
  least unstable of three unstable intermediates
  and is the one from which most of the product is
  formed.

Dr. Wolf's CHM 201 202
12-91
93
Nitration of (Trifluoromethyl)benzenePartial
Rate Factors

• All of the available ring positions in
  (trifluoromethyl)benzene are much less reactive
  than a single position of benzene.
• A CF3 group deactivates all of the ring
  positions but the degree of deactivation is
  greatest at the ortho and para positons.

Dr. Wolf's CHM 201 202
12-92
94
Theory of Directing Effects
95
Substituent Effects in ElectrophilicAromatic
SubstitutionActivating Substituents
Dr. Wolf's CHM 201 202
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96
Table 12.2
Classification of Substituents in Electrophilic
Aromatic Substitution Reactions

• Very strongly activating
• Strongly activating
• Activating
• Standard of comparison is H
• Deactivating
• Strongly deactivating
• Very strongly deactivating

Dr. Wolf's CHM 201 202
12-94
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Generalizations

• 1. All activating substituents are ortho-para
  directors.
• 2. Halogen substituents are slightly
  deactivating but ortho-para directing.
• 3. Strongly deactivating substituents are meta
  directors.

Dr. Wolf's CHM 201 202
12-95
98
Electron-Releasing Groups (ERGs)

• are ortho-para directing and activating

ERG
ERGs include R, Ar, and CC
Dr. Wolf's CHM 201 202
12-96
99
Electron-Releasing Groups (ERGs)

• are ortho-para directing and strongly activating

ERG
ERGs such as OH, and OR arestrongly activating
Dr. Wolf's CHM 201 202
12-97
100
Nitration of Phenol

• occurs about 1000 times faster than nitration of
  benzene

HNO3

44
56
Dr. Wolf's CHM 201 202
12-98
101
Bromination of Anisole

• FeBr3 catalyst not necessary

Br2
aceticacid
90
Dr. Wolf's CHM 201 202
12-99
102
Oxygen Lone Pair Stabilizes Intermediate

H
H
H
H
Br
H

• all atomshave octets

Dr. Wolf's CHM 201 202
12-100
103
Electron-Releasing Groups (ERGs)
ERG

• ERGs with a lone pair on the atom
  directlyattached to the ring are ortho-para
  directingand strongly activating

Dr. Wolf's CHM 201 202
12-101
104
Examples

• All of these are ortho-para directingand
  strongly to very strongly activating

Dr. Wolf's CHM 201 202
12-102
105
Lone Pair Stabilizes Intermediates forortho and
para Substitution

• comparable stabilization not possible for
  intermediate leading to meta substitution

Dr. Wolf's CHM 201 202
12-103
106
Substituent Effects in ElectrophilicAromatic
SubstitutionStrongly Deactivating Substituents
Dr. Wolf's CHM 201 202
12-104
107
ERGs Stabilize Intermediates forortho and para
Substitution
Dr. Wolf's CHM 201 202
12-105
108
Electron-withdrawing Groups (EWGs)
DestabilizeIntermediates for ortho and para
Substitution
EWG
EWG
X
H
H
H


H
H
H
H
H
X
H
H

• CF3 is a powerful EWG. It is strongly
  deactivating and meta directing

Dr. Wolf's CHM 201 202
12-106
109
Many EWGs Have a Carbonyl GroupAttached Directly
to the Ring
EWG

• All of these are meta directing and strongly
  deactivating

Dr. Wolf's CHM 201 202
12-107
110
Other EWGs Include
EWG
NO2
SO3H

• All of these are meta directing and strongly
  deactivating

Dr. Wolf's CHM 201 202
12-108
111
Nitration of Benzaldehyde
HNO3
H2SO4
75-84
Dr. Wolf's CHM 201 202
12-109
112
Problem 12.14(a) page 468
Cl
Cl2
FeCl3
62
Dr. Wolf's CHM 201 202
12-110
113
Disulfonation of Benzene
HO3S
SO3
SO3H
H2SO4
90
Dr. Wolf's CHM 201 202
12-111
114
Bromination of Nitrobenzene
Br
Br2
NO2
NO2
Fe
60-75
Dr. Wolf's CHM 201 202
12-112
115
Substituent Effects in ElectrophilicAromatic
SubstitutionHalogens

• F, Cl, Br, and I are ortho-para directing,but
  deactivating

Dr. Wolf's CHM 201 202
12-113
116
Nitration of Chlorobenzene
HNO3


H2SO4
69
1
30

• The rate of nitration of chlorobenzene is about
  30 times slower than that of benzene.

Dr. Wolf's CHM 201 202
12-114
117
Nitration of Toluene vs. Chlorobenzene
Cl
0.029
0.029
0.009
0.009
0.137
Dr. Wolf's CHM 201 202
12-115
118
Halogens

• thus, for the halogens, the inductive and
  resonance effects run counter to each other, but
  the former is somewhat stronger
• the net effect is that halogens are deactivating
  but ortho-para directing

119
Multiple Substituent Effects
Dr. Wolf's CHM 201 202
12-116
120
The Simplest Case

• all possible EAS sites may be equivalent

CH3
CCH3
AlCl3

CH3
99
Dr. Wolf's CHM 201 202
12-117
121
Another Straightforward Case
CH3
Br
NO2
86-90

• directing effects of substituents reinforceeach
  other substitution takes place orthoto the
  methyl group and meta to the nitro group

Dr. Wolf's CHM 201 202
12-118
122
Generalization

• regioselectivity is controlled by themost
  activating substituent

Dr. Wolf's CHM 201 202
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The Simplest Case

• all possible EAS sites may not be equivalent

strongly activating
Br2
aceticacid
87
Dr. Wolf's CHM 201 202
12-120
124
When activating effects are similar...
CH3
NO2
C(CH3)3
88

• substitution occurs ortho to the smaller group

Dr. Wolf's CHM 201 202
12-121
125
Steric effects control regioselectivity
whenelectronic effects are similar
98

• position between two substituents is
  lastposition to be substituted

Dr. Wolf's CHM 201 202
12-122
126
Regioselective Synthesis of Disubstituted
Aromatic Compounds
Dr. Wolf's CHM 201 202
12-123
127
Factors to Consider

• order of introduction of substituents to ensure
  correct orientation

Dr. Wolf's CHM 201 202
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Synthesis of m-Bromoacetophenone

• Which substituent should be introduced first?

Dr. Wolf's CHM 201 202
12-125
129
Synthesis of m-Bromoacetophenone
para

• If bromine is introduced first,
  p-bromoacetophenone is major product.

meta
Dr. Wolf's CHM 201 202
12-126
130
Synthesis of m-Bromoacetophenone
Br2
AlCl3
AlCl3
Dr. Wolf's CHM 201 202
12-127
131
Factors to Consider

• order of introduction of substituents to ensure
  correct orientation
• Friedel-Crafts reactions (alkylation, acylation)
  cannot be carried out on strongly deactivated
  aromatics

Dr. Wolf's CHM 201 202
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Synthesis of m-Nitroacetophenone

• Which substituent should be introduced first?

Dr. Wolf's CHM 201 202
12-129
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Synthesis of m-Nitroacetophenone

• If NO2 is introduced first, the next step
  (Friedel-Crafts acylation) fails.

Dr. Wolf's CHM 201 202
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Synthesis of m-Nitroacetophenone
O2N
HNO3
H2SO4
AlCl3
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Factors to Consider

• order of introduction of substituents to ensure
  correct orientation
• Friedel-Crafts reactions (alkylation, acylation)
  cannot be carried out on strongly deactivated
  aromatics
• sometimes electrophilic aromatic substitution
  must be combined with a functional group
  transformation

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Synthesis of p-Nitrobenzoic Acid from Toluene

• Which first? (oxidation of methyl group or
  nitration of ring)

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Synthesis of p-Nitrobenzoic Acid from Toluene
nitration givesm-nitrobenzoicacid
oxidation givesp-nitrobenzoicacid
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Synthesis of p-Nitrobenzoic Acid from Toluene
HNO3
Na2Cr2O7, H2O H2SO4, heat
H2SO4
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Substitution in Naphthalene
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Naphthalene
H
H
1
H
H
2
H
H
H
H

• two sites possible for electrophilicaromatic
  substitution
• all other sites at which substitution can
  occurare equivalent to 1 and 2

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EAS in Naphthalene
AlCl3
90

• is faster at C-1 than at C-2

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EAS in Naphthalene
E
E
H
H

• when attack is at C-1
• carbocation is stabilized by allylic resonance
• benzenoid character of other ring is maintained

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EAS in Naphthalene
E
H

• when attack is at C-2
• in order for carbocation to be stabilized by
  allylic resonance, the benzenoid character of the
  other ring is sacrificed

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Substitution inHeterocyclic Aromatic Compounds
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Generalization

• There is none.
• There are so many different kinds of
  heterocyclicaromatic compounds that no
  generalizationis possible.
• Some heterocyclic aromatic compoundsare very
  reactive toward electrophilicaromatic
  substitution, others are very unreactive..

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Pyridine

• Pyridine is very unreactive it
  resemblesnitrobenzene in its reactivity.
• Presence of electronegative atom (N) in
  ringcauses p electrons to be held more strongly
  thanin benzene.

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Pyridine
SO3, H2SO4
HgSO4, 230C
71

• Pyridine can be sulfonated at high temperature.
• EAS takes place at C-3.

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Pyrrole, Furan, and Thiophene

• Have 1 less ring atom than benzene or pyridine
  to hold same number of p electrons (6).
• p electrons are held less strongly.
• These compounds are relatively reactive toward
  EAS..

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Example Furan
BF3

CCH3
O
O
75-92

• undergoes EAS readilyC-2 is most reactive
  position

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End of Chapter 12 (Part a)