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NO2
HONO2 Nitration
H2SO4
SO3 SO3H
Sulfonation
H2SO4
RCl, AlCl3 R
Friedel- Crafts Alkilation
(R can rearrange)
O O
R C Cl, AlCl3 C R
Friedel-Crafts Acylation
The Clemmensen Reduction
Rearrangements of the carbon chain do not occur
in Friedel-Crafts acylation, because acylium ion is
more stable than most other carbocations.
O
O
C
AlCl3 CH2CH3
+ CH3CH2CCl + HCl
HCl, reflux
ethyl phenyl ketone
(90%) propyl benzene
(80%)
Exercise:
Starting with benzene and the appropriate acyl
chloride out line the synthesis of each of the following:
a. butyl benzene
b. (CH3)2CHCH2CH2C6H5
c. benzophenone (C6 H5COC 6H5)
The substitution reaction of the aromatic rings
and the reaction of the side chains of alkyl- and
alkenyl benzenes, offer us a powerful set of
reaction for organic synthesis.
We shall be able to synthesize a large number of
benzene derivatives.
Part of the skill in planning a synthesis is in the
deciding in which reactions should be carried out.
Example: If we want to synthesize
o-bromonitrobenzene we should introduce the
bromine into the ring first because it is an ortho-
para director.
Br Br Br
Br2 HNO3 NO2
+
FeBr3 H2SO4
o-bromonitrobenzene NO2
p-bromonitrobenzene
N C
R O2N
X +
R3N
strongly
deactivating
Reaction of the side chain of alkyl benzenes
Halogenation
CH3 CH2Cl CHCl2 CCl3
Cl2 Cl2 Cl2
h h h
Oxidation
(1)KMnO4, OH-,heat
CH3 CO2H
(2) H3O+
Exercises:
Starting with benzene, outline a synthesis of
(a) m-chlorotoluene
(b) m-chloroethylbenzene
(c) m-nitrobenzoic acid
REPLACEMENT REACTION
OF ARENEDIAZONIUM SALTS
Diazonium salts are highly useful intermediates in
the synthesis of aromatic compounds, because
the azonium group can be replaced by any one of
a number of other atoms or group, including F, -
Cl, -Br, -I, -CN, -OH, and
-H
Diazonium salts are almost always prepared by
diazotizing primary aromatic amines. Primary
arylamines can be synthesized through reduction
of nitro compounds that are readily available
throught direct nitration reaction.
Most arenediazonium unstable at
temperatures above 5-10o C, and many
explode when dry.
Replacement by -OH
Cu2O
H3C N2+HSO4- H3C OH
2+
Cu , H2O
p-toluenediazonium p-cresol
hydrogen sulfate (93%)
The Sulfa Drugs
(-CH3CO2H) 80oC,-H2O
acetanilide SO2Cl
aniline
p-acetamidobenzene-
sulfonyl chloride
O
NH2 NHCCH3 (-HCl)
1. dilute HCl, heat H2N-R
2. HCO3
SO2NHR SO2NHR
sulfanilamide
Exercise:
NH2
O
(1) H2O, H2SO4,heat
CH3CO- +
(2) OH-
NO2 p-nitroaniline
Synthesize o-nitroaniline
O O O
NH2 NHCCH3 NHCCH3
NHCCH3
CH3COCl H2SO4 conc. HNO3 NO2
heat
NH2
NO2 (1) H2O, H2SO4,heat
(2) OH-
Exercises:
Starting with aniline, outline a synthesis of :
a. p-nitroaniline
b. 4-bromo-2-nitroaniline