ELECTROPHILIC AROMATIC SUBSTITUTION

ArH + E+ Ar-E + H+

or E

+ E+ + H+

(i) A halo substituent , -X (Hologenation)

(ii) A nitro group , -NO2 (Nitration)
(iii) An alkyl group , -R (Friedel-Crafts alkylation)
(iv) An acyl group , -COR (Friedel-Crafts acylation)
1) Halogenation
Cl
FeCl3
+ Cl2 + HCl
25o
chlorobenzene (90%)

Br
FeBr3 + HBr
+ Br2

bromobenzene (75%)

2) Nitration
NO2
+ HNO3 + H2SO4 + H3O+ + HSO4-
50o

3) Friedel-Crafts reaction

R
AlCl3
+ R-X + HX Alkylation

alkylbenzene
O
O AlCl3 C
R
+ R-C-Cl + HCl Acylation
A- Friedel-Crafts Alkylation

CH3 CH3

AlCl3 CH3Cl
+ CH3Cl etc.
AlCl3

CH3

B- Friedel-Crafts Acylation
O
O C-CH3
AlCl3
+ CH3-C-Cl + HCl
80o
acetyl chloride acetophenone 97%
(methyl phenyl ketone)

O O
CH3C AlCl3 C-CH3
+ O
80o + CH3COOH
CH3C
O
acetic anhydride

Some synthetic applications of Friedel-Crafts acylation:

O
O C-CH2CH3
AlCl3
+ CH3CH2CCl + HCl
propionyl chloride
ethyl phenyl ketone
Zn/Hg/HCl/ 1)NH2NH2/2)NaOEt/
Clemmensen reduction Wolf-Kishner reduction

CH2CH2CH3

propylbenzene
Activating groups, that cause the ring to be more reactive than

o- , p-directors m-directors

strongly activating
strongly deactivating
-O-
-NH2, -NHR, -NR2 -NO2
-OH -NR3+
moderately activating -CF3, -CCl3

-NHCOCH3, -NHCOR moderately deactivating

-OCH3, -OR
-C N
weakly activating
-SO3H
-CH3, -C2H5, -R -COOH, -COOR
-C6H5 -CHO, -COR
weakly deactivating

-F, -Cl, -Br, -I

Electrophilic substitution in synthesis of benzene derivatives

1) Synthesis of p-chloronitrobenzene:

(I) Cl (II) Cl

Cl2/Fe HNO3
H2SO4
NO2

2) Synthesis of m-chloronitrobenzene:
 (I) NO2 (II) NO2
HNO3 Cl2/Fe
H2SO4
Cl
3) Synthesis of p-nitrobenzoic acid from toluene:

CH3
CH3 CH3
HNO3 NO2
+
H 2S O 4
NO2

COOH

NO2

CH3 COOH
COOH
+ HNO3
KMnO4/H
H2SO4
NO2