Aromatic Substitution reactions:

(a) Electrophilic substitution

(b) Nucleophilic Substitution reactions

Electrophilic Aromatic Substitution
Electrophilic addition reaction of an alkene
General Mechanism for Electrophilic Aromatic
Substitution Reactions
The following are the five most common electrophilic
aromatic substitution reactions:
No deuterium/hydrogen isotope effect in most cases.

If the hydrogen departed

• Before the electrophile added

• Or if the arrival of the electrophile and the departure of the
proton were simultaneous

Then we would expect an isotope effect on the rate of reaction if we

replace H by its more massive isotope D

The lack of an isotope effect means that the proton is lost after the
rds.
Isolation of Arenium Ion Intermediates:

Even the simplest arenium ion from benzene has been

detected by NMR at low temperatures (-134 oC).
Halogenation of Benzene
Comparison with Alkenes
• Moister in the air inactivate the catalyst
The order of reactivity of halogen is

F2 > Cl2 > Br2 > I2

Controlled fluorination is difficult.
Nitration of Benzene
Sulfonation of Benzene
Effect of Substitution

➢ Nitration of Toluene is 25 times

faster than benzene.
➢ Nitrobenzene is much less reactive
than benzene.

• Activating groups
• Deactivating groups
• Inductive effect
• Resonance effect
Effect of substituent on orientation
 Alkyl group

• Inductive stabilization

• Activating group

• Ortho/ para directing

The ortho-para ratio
Substituents with non bonding electrons

• 10000 times faster than benzene

• Resonance donating
 Deactivating groups

• 100000 times less reactive than benzene

• Meta directing
 Halogens substituents

Deactivating but ortho para directing

Rate of nitration in benzene derivatives
R in C6H5R Relative rate
OH 1,000
CH3 25
H 1
CH2Cl 0.71
I 0.18
F 0.15
Cl 0.033
Br 0.030
CO2Et 0.0037
NO2 6 x 10-8
NMe3+ 1.2 x 10-8
Friedel–Crafts Acylation of Benzene
Gatterman-Koch formylation
Friedel–Crafts Alkylation of Benzene
For Primary Carbocation
Designing a synthetic scheme
 90 %

+ traces of ortho product

NHCOCH3 NHCOCH3 NHCOCH3

NO2
HNO3
+ Conc. H2SO4 H2SO4

SO3H SO3H

dil. H2SO4

NHCOCH3

NO2
SNAr reaction (substitution nucleophilic Aromatic)
Nature of the leaving group
does not affect the overall
reaction rate.

The only requirement is that

the incoming group be a
stronger base than the group
that is being replaced.
 1 2

EWD groups favor 1 ED groups favor 2

 X

-H

X X

Best leaving group will remove from both.