Reactions of Arenes:

1
Chapter 12

• Reactions of Arenes
• Electrophilic Aromatic Subsititution

2
Electrophilic Aromatic Substitution
3
Mechanism of Electrophilic Aromatic Substitution

• Step 1 Electrophile attacks p electrons of ring
  forming cyclohexadienyl cation.

highly endothermic carbocation is allylic, but
not aromatic
4
Mechanism of Electrophilic Aromatic Substitution

• Step 2 Loss of a proton restores aromaticity of
  ring.

H
H
E
H

H
H
H
highly exothermic this step restores
aromaticity of ring
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(No Transcript)
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The Cyclohexadienyl Cation is Stabilized by
Resonance.
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Nitration of Benzene
H2SO4

HONO2

H2O
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How the Nitronium is Formed
H2SO4
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Sulfonation of Benzene
heat

HOSO2OH

H2O
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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 Bromine-Ferric Bromide Complex

FeBr3
Lewis base
Lewis acid
The Br2-FeBr3 complex is more electrophilic than
Br2 alone.
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Friedel-Crafts Alkylation of Benzene
AlCl3

(CH3)3CCl

HCl
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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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Rearrangements in Friedel-Crafts Alkylations
Carbocations are intermediates. Therefore,
rearrangements can occur
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Rearrangements in Friedel-Crafts Alkylations


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Reactions Related to Friedel-Crafts Alkylations
H2SO4

Cyclohexylbenzene(65-68)
Cyclohexene is protonated by sulfuric acid,
giving cyclohexyl cation which attacks the
benzene ring
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Friedel-Crafts Acylation of Benzene
O
O
CCH2CH3
AlCl3

CH3CH2CCl

HCl
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Acid Anhydrides
can be used instead of acyl chlorides
AlCl3

Acetophenone(76-83)
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Acylation-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.
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Acylation-Reduction
(CH3)2CHCH2Cl
CH2CH(CH3)3
AlCl3
No! Friedel-Crafts alkylation of benzene using
isobutyl chloride fails because of rearrangement.
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Example of Acylation-Reduction
(CH3)2CHCH2Cl
CH2CH(CH3)3
AlCl3
No! Friedel-Crafts alkylation of benzene using
isobutyl chloride fails because of rearrangement.
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Tab. 12.1
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Rate and Regioselectivity of Electrophilic
Aromatic Substitution

• General Principles
• 1. Substituents which release electrons activate
  the ring toward substitution. Substituents which
  withdraw electrons deactivate the ring toward
  substitution.
• 2. The ortho and para positions are most effected
  by electron releasing or withdrawing substituents.

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The Nitration of Toluene


34
3
63
o- and p-nitrotoluene together comprise 97 of
the product a methyl group is an ortho-para
director
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The Nitration of (Trifluoromethyl)benzene


3
91
6
m-nitro(trifluoromethyl)benzene comprises 91 of
the product a trifluoromethyl group is a meta
director
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Nitration of Toluene vs Tert-butyl benzene
tert-Butyl is activating and ortho-para
directing tert-Butyl crowds the ortho positions
and decreases the rate of attack at those
positions.
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Rate Factors for (Trifluoromethyl)benzene
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.
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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

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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.

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Electron Releasing Groups (ERG)
are ortho-para directing and activating
ERG
ERGs include R, Ar, and CC
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Electron Releasing Groups (ERG)
ERG
ERGs with a lone pair on the atom
directlyattached to the ring are ortho-para
directingand strongly activating
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Examples
All of these are ortho-para directingand
strongly to very strongly activating
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Many EWGs Have a Carbonyl GroupAttached Directly
to the Ring
EWG

• All of these are meta directing and strongly
  deactivating

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Other EWGs Include
EWG
NO2
SO3H

• All of these are meta directing and strongly
  deactivating

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Halogens

• Halogen substituents on a benzene ring are
  slightly deactivating ortho-para directors.

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Halogens
HNO3


H2SO4
69
1
30
The rate of nitration of chlorobenzene is about
30 times slower than that of benzene.
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Multiple Substituent Effects

• In general
• 1. Regioselectivity is governed by the most
  activating group.
• 2. Steric Hinderance affects substitution.

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Example
strongly activating
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Steric Effect
position between two substituents is
lastposition to be substituted
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Example (when effects are similar)
substitution occurs ortho to the smaller group
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Substituent Effects on SynthesisSynthesis of
m-Nitroacetophenone

• Which substituent should be introduced first?

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Electrophilic Substitution of 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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Substitution in Heterocyclic Aromatic Compounds

• There are many Heterocyclic Aromatic Compounds.
  Therefore, no generalization can adequately apply
  to all.

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Pyridine
Pyridine is very unreactive it
resemblesnitrobenzene in its reactivity. Presence
of electronegative atom (N) in ringcauses ?
electrons to be held more strongly thanin
benzene.
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Pyrole, Furan, and Thiophene
Have 1 less ring atom than benzene or pyridine
to hold same number of ? electrons (6). ?
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