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 SO3H

Br2, Fe
Br

CH3CH2-Br
CH2CH3
AlCl3
toluene

CH3 CH3 CH3

HNO3 NO2
+
H2SO4
NO2
faster than the same
reactions with
CH3 CH3 CH3
SO3 benzene
SO3H
+
H2SO4

SO3H

CH3 CH3
CH3
Br
Br2, Fe +

Br
nitrobenzene

NO2 NO2
HNO3
H2SO4
NO2

slower than the same

reactions with
NO2 NO2 benzene
SO3
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
 Common substituent groups and their effect on EAS:

-NH2, -NHR, -NR2

-OH
-OR
-NHCOCH3
ortho/para directors
increasing reactivity

-C6H5
-R
-H
-X
-CHO, -COR
-SO3H
-COOH, -COOR
meta directors
-CN
-NR3+
-NO2
OCH3 OCH3 OCH3
Br2, Fe Br
+ faster than benzene

Br

CHO CHO

HNO3, H2SO4 slower than benzene

NO2

Br Br Br
SO3H
H2SO4, SO3
+ 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
HNO3, H2SO4 NO2

CH3 CH3

CHO CHO CHO

Cl2, Fe Cl
+
OCH3 OCH3 OCH3
Cl
Orientation and synthesis. Order is important!
synthesis of m-bromonitrobenzene from benzene:

NO2 NO2
HNO3 Br2, Fe

H2SO4
Br

synthesis of p-bromonitrobenzene from benzene:

Br Br Br
Br2, Fe HNO3 NO2
+
H2SO4
NO2

You may assume that you can separate a pure para-

isomer 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
Br
Br NO2
Br2, Fe Br2, Fe + HNO3
H2SO4
Br Br

separate pure para isomer from ortho/para mixture

NO2 NO2
NO2 NO2
Br
HNO3 Br2, Fe Br2, Fe
+
H2SO4 Br
Br Br
Br

cannot assume that these can be separated!

synthesis of benzoic acids by oxidation of –CH3

CH3 COOH
CH3Br KMnO4

AlCl3 heat

CH3 COOH COOH

CH3Br KMnO4 HNO3
AlCl3 heat H2SO4
NO2

CH3 CH3 COOH

CH3Br HNO3 KMnO4

AlCl3 H2SO4 heat

NO2 NO2

+ ortho-
nitration

+
HO-NO2 + H2SO4  H2O-NO2 + HSO4-

+ +
H2O-NO2  H2O + NO2

H2SO4 + H2O  HSO4- + H3O+

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

 nitration:

1) HONO2 + 2 H2SO4 H3O+ + 2 HSO4- + NO2+

electrophile
RDS
2) + NO2+
resonance

NO2 NO2 NO2

H H H

NO2

H
 Mechanism for nitration:

1) HONO2 + 2 H2SO4 H3O+ + 2 HSO4- + NO2+

RDS NO2
2) + NO2+
H

NO2
3) NO2 + H+
H
Mechanism for sulfonation:

1) 2 H2SO4 H3O+ + HSO4- + SO3

RDS
SO3-
2) + SO3
H

SO3-
3) SO3- + H+
H

4) SO3- + H3O+ SO3H + H2O

Mechanism for halogenation:

1) Cl2 + AlCl3 Cl-Cl-AlCl3

RDS Cl
2) + Cl-Cl-AlCl3 + AlCl4-
H

Cl
3) + AlCl4- Cl + HCl + AlCl3
H
Mechanism for Friedel-Crafts alkylation:

1) R-X + FeX3 R + FeX4-

RDS R
2) + R
H

R
3) + FeX4- R + HX + FeX3
H
Mechanism for Friedel-Crafts with an alcohol & acid

1) R-OH + H+ ROH2+

2) ROH2+ R + H2O

RDS R
3) + R
H

R
4) R + H+
H
Mechanism for Friedel-Crafts with alkene &
acid:

1) C C + H+ R

RDS R
+ R
2)
H

R
3) R + H+
H

electrophile in Friedel-Crafts alkylation = carbocation

“Generic” Electrophilic Aromatic Substitution mechanism:

RDS Y
1) + Y+Z- + Z-
H

Y
2) + Z- Y + HZ
H
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
unshared pair of electrons on the nitrogen
N
resonance donating groups
H
(weaker inductive withdrawal)

R
N
R

R strong inductive withdrawal

R N (no unshared pair of electrons on the
R nitrogen & no resonance possible
 resonance donation
O (weaker inductive withdrawal)
H

resonance donation
O (weaker inductive withdrawal)
R

O
H3C C N resonance donation
(weaker inductive withdrawal)
H
 resonance donation

inductive donation
H3C sp3 sp2 ring carbon

X— 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 resonance and
N inductive withdrawal
O
 Common substituent groups and their effect on reactivity in EAS:

-NH2, -NHR, -NR2

-OH
-OR
-NHCOCH3 electron donating
-C6H5
increasing reactivity

-R
-H
-X
-CHO, -COR
-SO3H
-COOH, -COOR electron withdrawing
-CN
-NR3+
-NO2
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.
H Y

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.
H Y

NO2
CF3

electron withdrawing = deactivating & meta-director

PO3H

electron withdrawing = deactivating & meta-director

PH2

electron donating = activating & ortho-/para-director

 Br2, Fe
Br + ortho-

Br2, Fe
NO2 Br NO2 + ortho-

O
Br2, Fe O
+ ortho-
O
O Br
How to draw resonance structures for EAS

Y Y
H

Y Y
H H
G G G
Y Y Y
H H H ortho-attack

G G G

meta-attack
Y Y Y
H H H

G G
G
para-attack

H Y H Y
H Y
 G G
Y
H

H Y

If G is an electron donating group, these structures are

especially stable.
G G G
Y Y Y
H H H ortho-attack

G G G

meta-attack
Y Y Y
H H H

G G
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 Eact’s for ortho-/para- are lower and the
rates are faster.

Electron donating groups direct ortho-/para- in EAS

 G G
Y
H

H Y

If G is an electron withdrawing group, these structures

are especially unstable.
G G G
Y Y Y
H H H ortho-attack

G G G

meta-attack
Y Y Y
H H H

G G
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 Eact’s 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.
 X X X X
Y Y Y Y
H H H H
ortho-

X X X

meta-
Y Y Y
H H H

X X X
X

para-

H Y H Y H Y
H Y

halogens are deactivating in EAS but direct ortho and para

 Common substituent groups and their effect on EAS:

-NH2, -NHR, -NR2

-OH
-OR
-NHCOCH3
ortho/para directors
increasing reactivity

-C6H5
-R
-H
-X
-CHO, -COR
-SO3H
-COOH, -COOR
meta directors
-CN
-NR3+
-NO2