Electrophilic Aromatic Substitution (Aromatic compounds)

Ar-H = aromatic compound

1. Nitration
Ar-H +

HNO3, H2SO4 Ar-NO2 + H2O

2. Sulfonation
Ar-H + H2SO4, SO3 Ar-SO3H + H2O
3. Halogenation
Ar-H + X2, Fe Ar-X + HX
4. Friedel-Crafts alkylation
Ar-H + R-X, AlCl3 Ar-R + HX

Friedel-Crafts alkylation (variations)

a) Ar-H + R-X, AlCl3 Ar-R + HX

b) Ar-H + R-OH, H+ Ar-R + H2O

c) Ar-H + Alkene, H+ Ar-R

HNO3

NO2

H2SO4
SO3
H2SO4

Br2, Fe

SO3H

Br

CH3CH2-Br
AlCl3

CH2CH3

toluene
CH3

CH3

CH3
HNO3

NO2

H2SO4

+
NO2

CH3
SO3

CH3

CH3
SO3H
+

H2SO4

SO3H
CH3

CH3

CH3
Br2, Fe

Br

+
Br

faster than the same

reactions with
benzene

nitrobenzene
NO2

NO2
HNO3
H2SO4

NO2
SO3

NO2

slower than the same

reactions with
benzene

NO2

H2SO4
SO3H

NO2

NO2
Cl2, Fe
Cl

Substituent groups on a benzene ring affect electrophilic

aromatic substitution reactions in two ways:

1) reactivity
activate (faster than benzene)
or deactivate (slower than benzene)
2) orientation
ortho- + para- direction
or meta- direction

-CH3
activates the benzene ring towards EAS
directs substitution to the ortho- & para- positions

-NO2
deactivates the benzene ring towards EAS
directs substitution to the meta- position

increasing reactivity

Common substituent groups and their effect on EAS:

-NH2, -NHR, -NR2
-OH
-OR
-NHCOCH3
-C6H5
-R
-H
-X
-CHO, -COR
-SO3H
-COOH, -COOR
-CN
-NR3+
-NO2

ortho/para directors

meta directors

OCH3

Br2, Fe

OCH3

OCH3
Br

faster than benzene

+
Br

CHO

CHO
slower than benzene

HNO3, H2SO4
NO2

Br

Br
H2SO4, SO3

Br
SO3H
+

slower than benzene

SO3H

If there is more than one group on the benzene

ring:
1. The group that is more activating (higher
on the list) will direct the next
substitution.
2. You will get little or no substitution
between groups that are meta- to each
other.

CH3

CH3

Br2, Fe
Br

OH

OH

NHCOCH3

NHCOCH3
NO2

HNO3, H2SO4

CH3

CH3
CHO

CHO

CHO

Cl2, Fe

Cl
+

OCH3

OCH3
Cl

OCH3

Orientation and synthesis. Order is important!

synthesis of m-bromonitrobenzene from benzene:
NO2

HNO3

NO2

Br2, Fe

H2SO4

Br

synthesis of p-bromonitrobenzene from benzene:

Br
Br2, Fe

Br

Br

HNO3

NO2
+

H2SO4
NO2

You may assume that you can separate a pure paraisomer from an ortho-/para- mixture.

note: the assumption that you can separate a pure para

isomer from an ortho/para mixture does not apply to any
other mixtures.
synthesis of 1,4-dibromo-2-nitrobenzene from benzene
Br

Br

Br

Br2, Fe

Br2, Fe

Br

Br

NO2

HNO3
H2SO4

Br

Br

separate pure para isomer from ortho/para mixture

NO2
HNO3
H2SO4

NO2

NO2
Br2, Fe

NO2
Br

Br2, Fe
Br

+
Br

Br

Br
cannot assume that these can be separated!

synthesis of benzoic acids by oxidation of CH3

CH3
CH3Br

COOH
KMnO4

AlCl3

heat

CH3

COOH

CH3Br

KMnO4

AlCl3

heat

COOH
HNO3
H2SO4

COOH

CH3

CH3
CH3Br

HNO3

KMnO4

AlCl3

H2SO4

heat
NO2
+ ortho-

NO2

NO2

nitration
HO-NO2 + H2SO4
+
H2O-NO2

+
H2O-NO2 + HSO4-

+
H2O + NO2

H2SO4 + H2O

HSO4- + H3O+

HNO3 + 2 H2SO4 H3O+ + 2 HSO4- + NO2+

nitration:

H3O+

1) HONO2 + 2 H2SO4

2 HSO4- + NO2+

electrophile
2)

NO2+

RDS

resonance

NO2

NO2

NO2

NO2
H

Mechanism for nitration:

H3O+

1) HONO2 + 2 H2SO4

2)

3)

NO2+

RDS

2 HSO4- + NO2+

NO2
H

NO2
H

NO2

+ H+

Mechanism for sulfonation:

1)

H3O+

2 H2SO4

RDS
2)

3)

4)

+ SO3

HSO4-

SO3

SO3H

SO3H

SO3- + H3O+

SO3-

H+

SO3H

+ H2O

Mechanism for halogenation:

1)

Cl-Cl-AlCl3

Cl2 + AlCl3

2)

Cl-Cl-AlCl3

RDS

Cl
H

Cl
3)

AlCl4-

Cl

+ AlCl4-

+ HCl + AlCl3

Mechanism for Friedel-Crafts alkylation:

1)

R-X

FeX3

+ R

2)

3)

R
RDS

FeX4R
H

R
H

+ FeX4-

HX

+ FeX3

Mechanism for Friedel-Crafts with an alcohol & acid

1)

R-OH

2)

ROH2+

ROH2+

+ R

3)

4)

H+

+ H2O
RDS

R
H

R
H

+ H+

Mechanism for Friedel-Crafts with alkene &

acid:
1)

C C

+ R

2)

3)

H+

RDS

R
H

R
H

H+

electrophile in Friedel-Crafts alkylation = carbocation

Generic Electrophilic Aromatic Substitution mechanism:

2)

Y+Z-

1)

Y
H

Z-

RDS

Y
+

Z-

HZ

Why do substituent groups on a benzene ring affect the

reactivity and orientation in the way they do?

electronic effects, pushing or pulling electrons by

the substituent.

Electrons can be donated (pushed) or withdrawn

(pulled) by atoms or groups of atoms via:
Induction due to differences in electronegativities
Resonance delocalization via resonance

H
N
H
R
N
H

unshared pair of electrons on the nitrogen

resonance donating groups
(weaker inductive withdrawal)

R
N
R
R
R N
R

strong inductive withdrawal

(no unshared pair of electrons on the
nitrogen & no resonance possible

O
H

O
R

O
H3C C N
H

resonance donation
(weaker inductive withdrawal)

resonance donation
(weaker inductive withdrawal)

resonance donation
(weaker inductive withdrawal)

resonance donation

H3C

inductive donation
sp3
sp2 ring carbon

inductive withdrawal

O
C
H

O
C
R
resoance withdrawal and
inductive withdrawal
O
C
HO

O
C
RO

N C

resonance and
inductive withdrawal

O
N
O

resonance and
inductive withdrawal

increasing reactivity

Common substituent groups and their effect on reactivity in EAS:

-NH2, -NHR, -NR2

-OH
-OR
-NHCOCH3
-C6H5
-R
-H
-X
-CHO, -COR
-SO3H
-COOH, -COOR
-CN
-NR3+
-NO2

electron donating

electron withdrawing

Electron donating groups activate the benzene ring to

electrophilic aromatic substitution.

1. electron donating groups increase the electron density

in the ring and make it more reactive with
electrophiles.
2. electron donation stabilizes the intermediate
carbocation, lowers the Eact and increases the rate.

CH3

Electron withdrawing groups deactivate the benzene ring to

electrophilic aromatic substitution.

1. electron withdrawing groups decrease the electron density

in the ring and make it less reactive with electrophiles.
2. electron withdrawal destabilizes the intermediate
carbocation, raising the Eact and slowing the rate.

NO2

CF3
electron withdrawing = deactivating & meta-director

PO3H
electron withdrawing = deactivating & meta-director

PH2
electron donating = activating & ortho-/para-director

Br2, Fe

NO2

O
O

Br

+ ortho-

Br2, Fe
Br

Br2, Fe

NO2

+ ortho-

O
+ orthoO

Br

How to draw resonance structures for EAS

Y

Y
H

Y
H

Y
H

Y
H

Y
H

Y
H

Y
ortho-attack

meta-attack

G
para-attack

H Y

H Y

H Y

G
Y
H

H Y
If G is an electron donating group, these structures are
especially stable.

Y
H

Y
H

Y
H

Y
H

Y
ortho-attack

meta-attack

G
para-attack

H Y

H Y

H Y

Electron donating groups stabilize the intermediate

carbocations for ortho- and para- in EAS more than for
meta-. The Eacts for ortho-/para- are lower and the
rates are faster.

Electron donating groups direct ortho-/para- in EAS

G
Y
H
H Y

If G is an electron withdrawing group, these structures

are especially unstable.

Y
H

Y
H

Y
H

Y
H

Y
ortho-attack

meta-attack

G
para-attack

H Y

H Y

H Y

Electron withdrawing groups destabilize the intermediate

carbocations for ortho- and para- in EAS more than for
meta-. The Eacts for ortho-/para- are higher and the
rates are slower.

Electron withdrawing groups direct meta- in EAS

Halogens are electron withdrawing but are ortho/para

directing in EAS.

The halogen atom is unusual in that it is highly

electronegative but also has unshared pairs of electrons
that can be resonance donated to the carbocation.

Y
H

Y
H

ortho-

meta-

Y
H

Y
H

Y
H

X
para-

H Y

H Y

H Y

H Y

halogens are deactivating in EAS but direct ortho and para

increasing reactivity

Common substituent groups and their effect on EAS:

-NH2, -NHR, -NR2
-OH
-OR
-NHCOCH3
-C6H5
-R
-H
-X
-CHO, -COR
-SO3H
-COOH, -COOR
-CN
-NR3+
-NO2

ortho/para directors

meta directors