Reactions review: Benzene and aromatic compounds
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Because of its  electrons, benzene is a nucleophile and is attracted to electrophiles.
Due to the stability of aromatic  system, addition reactions aren’t favored.
Electrophilic aromatic substitution is the predominant reaction mechanism
Hydrogens are easily replaced by electrophilic substituent groups
H
+
Y+
B:
Y
+
HB
Y
resonance-stabilized
carbocation
H
H
Y
Y
Tip: The most common electrophilic substitutions (reactions 1 – 5) can be used synthetically to
provide starting points for preparation of other derivatives (6 – 10)
1) Halogenations: Aryl bromides, aryl chlorides and aryl iodides
FeCl3 can be used to generate an electrophilic
halogen cation from either Br2 or Cl2:
Br - Br + FeCl3
Br 2, FeCl3
Br + + -FeCl3Br
Cl2, FeCl3
Iodine cation is produced by reaction with a
strong oxidizer such as nitric acid or Cu2+:
HNO3
I2
2 I+ + 2 eI2 + 2 Cu2+
Br
I 2, CuCl2
Cl
I
2 I+ + 2Cu+
2) Nitration: Electrophile is a nitronium ion generated from nitric & sulfuric acids:
HNO3
+ H2SO4
O=N=O + H2O + HSO4-
H2SO4, HNO3
NO 2
3) Sulfonation/desulfonation: aryl sulfonates
The electrophile (+SO3H) generated from fuming sulfuric acid reacts with benzene.
The reverse, desulfonation occurs under conditions of heat and dilute acid
H3O+ + SO3
O = S = O + H2O
f uming H2 SO4
SO3H
OH
heat, dilute acid
3b) Alkali fusion:
f uming H SO4
2
Treatment of sulfonates with base produces
phenols
SO3H
1) NaOH
OH
2) H 3O+
heat, dilute acid
(4) & (5) Friedel-Crafts acylations and alkylations
Friedel-Crafts rxns are used to put an R group or an acyl group on benzene. Lewis acid AlCl3 used to
generate an electrophilic “acylium ion” from an acyl or alkyl halide. Either of these electrophilic C
species can undergo a substitution with benzene.
acyl:
alkyl:
Cl
R - C = O + AlCl3
[ R - C = O:
R - Cl + AlCl3
R+ + -AlCl4
R - C = O: ] +
-AlCl4
Alkylated aromatics: The Friedel-Crafts alkylation requires excess benzene, can’t take place with
vinyl or aryl halides due to unstable carbocations and rearrangement of the carbocation possible:
+
H2
C
H 2C
AlCl3
H
C
Cl
C
H2
CH 3
+
H2
C
CH 3
C
H2
CH 3
Aromatic ketones: The Friedel-Crafts acylation reaction requires excess AlCl3 due to tendency of
complexation with carbonyl group and water to hydrolyze the Al salts
O
1. AlCl3
+ H3C C
O
C
Cl
2. H2O
CH 3
+ Al(OH)3 + 3 HCl
Aromatic aldehydes: Benzaldehydes can’t be made by F-C rxn; use Gattermann-Koch formylation:
1) NaOH
2) H 3O+
Reactions that transform substituents: Reactions (1) – (5) can be starting points for
obtaining other substituents by transforming the product to another group
6) Grignard reactions with aryl halides: can prepare alcohols, benzoic acid
Mg, ether
OH
RCHO
Br
Mg Br
C
H
H 3O+
R
O
CO2
C
OH
H 3O+
7) Phenols from aromatic halides:
1) NaOH, H 2O,
o
Cl 340 C, 2500 psi
Elimination followed by addition:
Alkali fusion of benzene sulfonates also
produces phenols (see 3b)
2)
OH
H 3O+
8) Reductions of nitro or carbonyl groups:
Nitrobenzene to aniline:
Wolff-Kishner reduction:
O
SnCl2, H+
NO 2
NH 2
OH-
H2NN2H
H2
C
C
CH3
NaOH
9) Oxidations of alkyl or amine groups:
KMnO 4
CH 3
KMnO4 will oxidize any alkyl group
having benzylic H to a COOH group
COOH
H3O+
Amino group can be
oxidized back to nitro
CF3CO 3H
NH 2
NO 2
10) SN2 reactions at the benzylic carbon: Methyl group is brominated by NBS in a radical
substitution, then the Br can be replaced by nucleophiles in SN2 reaction

NBS
CH 3
CH 2
Nu-
Br
NaOH
CH2
Nu
Gilman
CN-
CH 2
CH 2
OH
CN
C CH2 CH 3
H2
CH 3
Synthesizing polysubstituted benzene derivatives: Does the order of substituent
placement matter? YES!
When making polysubstituted benzenes, consider how the first substituent affects both
the reactivity and orientation of the next substitution (consult Table 16.2)
Ex: Friedel-Crafts reaction won’t proceed when the ring already has a deactivator
Tips in planning synthesis:
 When ortho or para orientation is desired, put the activating group on first
 When meta orientation is desired, the deactivating group should go on first, provided
that it doesn’t completely deactivate the ring (exception is Friedel-Crafts rxn)
 Take advantage of methods to convert activating to deactivating groups
afterwards, for example CH3 to COOH or NH2 to NO2
Example: a multi-step synthesis of p-nitrobenzoic acid
O2N
CH 3
AlCl3
KMnO4
HNO3
CH 3Cl
H 2SO 4
CH 3
H 3O+
O2N
COOH