Reactions of Arenes:

Electrophilic Aromatic Substitution

H E
+ –
+E Y +H Y

part 1
Aromatic Compounds React
Differently Than Alkenes

Cl

+ Cl2 Addition
Cl

Cl
FeCl3
+ Cl2 Substitution
 H E
+ –
+E Y +H Y

Electrophilic aromatic substitutions include:

Nitration (-NO2)
Sulfonation (-SO3H)
Halogenation (-Br or –Cl)
Friedel-Crafts Alkylation (-R)
Friedel-Crafts Acylation
H H2SO4 NO2
+ HONO2
+ H2O

H heat SO2OH
+ HOSO2OH
+ H2O

H FeBr3 Br
+ Br2
+ HBr
H AlCl3 C(CH3)3
+ (CH3)3CCl
+ HCl

O
O
H AlCl3 CCH2CH3
+ CH3CH2CCl
+ HCl
Electrophilic Aromatic Substitution Mechanism

Step 1: attack of electrophile

on -electron system of aromatic ring

E+
H H H H E
H H H +
H
H H H H

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

Step 2: loss of a proton from the carbocation

intermediate

E H H H H
+ H E H
H
H H H+ H H

highly exothermic
this step restores aromaticity of ring
 Nitration of Benzene

NET REACTION

H H2SO4 NO2
+ HONO2
+ H2O

+
Electrophile is
•• O
••
N O ••
••
nitronium ion
Step 1a; Formation of Strong Electrophile

H
O O
H O N + H+ H O N
O + O

H
O +
H O N H2O + O N O
+ O
-
Step 1b: attack of nitronium cation
on -electron system of aromatic ring

NO2+
H H H H NO2
H H H +
H
H H H H

Step 2: Water molecule will abstract a proton

from the carbocation intermediate
H H
H H NO2
H NO2
H +
H H H H+
H H
 Sulfonation of Benzene

H heat SO2OH
+ HOSO2OH
+ H2O

•• •• –
•• O + O ••
••
Several electrophiles present: S
a major one is sulfur trioxide
•• O
••
 Halogenation of Benzene
NET REACTION
H FeBr3 Br
+ Br2
+ HBr

Electrophile is a Lewis acid-Lewis base

complex between FeBr3 and Br2.
+
•• •• •• •• –
•• Br Br •• + FeBr3 •• Br Br FeBr3
•• •• •• ••

Lewis base Lewis acid Complex

Friedel-Crafts Alkylation of Benzene

H AlCl3 C(CH3)3
+ (CH3)3CCl
+ HCl

H3C
Electrophile is +
C CH3
tert-butyl cation
H3C
 Role of AlCl3

acts as a Lewis acid to promote ionization

of the alkyl halide

+
•• •• –
(CH3)3C Cl •• + AlCl3 (CH3)3C Cl AlCl3
•• ••

+ •• –
(CH3)3C + •• Cl AlCl3
••
Rearrangements in Friedel-Crafts Alkylation

Carbocations are intermediates.

Therefore, rearrangements can occur

H C(CH3)3
AlCl3
+ (CH3)2CHCH2Cl

Isobutyl chloride tert-Butylbenzene

(66%)
 Friedel-Crafts Acylation of Benzene

O
O
H AlCl3 CCH2CH3
+ CH3CH2CCl
+ HCl

Electrophile is an acyl cation

+ •• +
CH3CH2C O •• CH3CH2C O ••
 Acylation-Reduction

permits primary alkyl groups to be attached

to an aromatic ring
H2NNH2, KOH,
O O
triethylene glycol,
H CR heat
RCCl
OR
AlCl3 Zn(Hg), HCl

CH2R
 Example: Prepare isobutylbenzene

(CH3)2CHCH2Cl CH2CH(CH3)3

AlCl3 isobutylbenzene

No! Friedel-Crafts alkylation of benzene using isobutyl

chloride fails because of carbocation rearrangement.

C(CH3)3
Actual Product
 Use Acylation-Reduction Instead

+ (CH3)2CHCCl

AlCl3 Zn(Hg) CH2CH(CH3)3

HCl
O

CCH(CH3)2
 Rate and Regioselectivity in
Electrophilic Aromatic Substitution

A substituent already present on the ring

can affect both the rate and regioselectivity
of electrophilic aromatic substitution.
 Effect on Rate

Activating substituents increase the rate

of EAS compared to that of benzene.

(-OH, -CH3)
Deactivating substituents decrease
the rate of EAS compared to benzene.

(-Cl, -NO2)
 Rate of Nitration Depends on
What is Already on the Ring

O-H CH3 H Cl NO2

1000 25 1 0.003 1 X 10 -7

Ring Activators Ring Deactivators

 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.
Placement of 2nd Substituent Depends
on What the 1st Substituent is
NO2 NO2
FeBr3
+ Br 2

Br

NO2

Br Br Br
H2SO4
+ HNO3 +

NO2

NO2 is a meta director;

while Br is an ortho /para director
 Nitration of Toluene

CH3 CH3 CH3 CH3

NO2
HNO3
+ +
acid
NO2
NO2
63% 3% 34%
o- and p-nitrotoluene together comprise 97%
of the product
a methyl group is an ortho-para director
 Mechanism
1. Form Strong Electrophile
2. Electrophile Adds to Benzene Ring to Form
the Most Stable Carbocation
E+
H H H H E
H H H +
H
H H H H

3. Restoration of Aromaticity
 Three Possible Carbocations May Be Formed
Carbocation Stability Controls Regioselectivity

CH3 CH3 CH3

NO2
H H H H H
H +
+ +
H H H H H H
NO2
H H NO2 H
gives ortho gives para gives meta

more stable less stable

 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
 para Nitration of Toluene

CH3 CH3 CH3

H H H + H H H
+ +
H H H H H H
H NO2 H NO2 H NO2
this resonance
form is a tertiary
carbocation
 meta Nitration of Toluene

CH3 CH3 CH3

H H H H H H
+ +

H H H H H + H
NO2 NO2 NO2
H H H
all the resonance forms of the rate-
determining intermediate in the meta nitration
of toluene have their positive charge on a
secondary carbon
 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.
 NET REACTION

OH OH OH

Br
FeBr3
+ Br 2 +

Br
Ortho, Para Attack
 Lone Pair Stabilizes Intermediates for
ortho and para Substitution

+ ERG + ERG
H
H H H
X

H H H H

H H X

comparable stabilization not possible for

intermediate leading to meta substitution
Meta Attack
 Ortho/Para Directors
A. Lone Pair on Atom Bond to Benzene Ring

O H N H N R

H R
-X ; -F, -Cl, -Br, -I
O R N R

B. Alkyl Groups Bond to Benzene Ring

-CH3
-CH2CH3