Organic Chemistry, 5th Edition

L. G. Wade, Jr.

Chapter 17
Reactions of
Aromatic Compounds

Jo Blackburn
Richland College, Dallas, TX
Dallas County Community College District
2003,Prentice Hall
 Electrophilic
Aromatic Substitution
Electrophile substitutes for a hydrogen on
the benzene ring.

=>
Chapter 17 2
Mechanism

=>
Chapter 17 3
 Bromination of Benzene
• Requires a stronger electrophile than Br2.
• Use a strong Lewis acid catalyst, FeBr3.
Br Br FeBr3 Br Br FeBr3
H Animation
H H
H
H H _
Br
Br Br FeBr3 + + FeBr4
H H
Animation
H H
H
H

Br Animation
+ HBr
Chapter 17
=>
4
Energy Diagram
for Bromination

=>
Chapter 17 5
 Chlorination
and Iodination
• Chlorination is similar to bromination.
Use AlCl3 as the Lewis acid catalyst.
• Iodination requires an acidic oxidizing
agent, like nitric acid, which oxidizes the
iodine to an iodonium ion.
+ +
H + HNO3 + 1/2 I2 I + NO2 + H2O

=>
Chapter 17 6
 Nitration of Benzene
Use sulfuric acid with nitric acid to form
the nitronium ion electrophile.
O O H O
_
H O S O H H O N H O N + HSO4
+
O O O

H O O
NO2+ then forms a
H O N H2O + N+
+ sigma complex with
O O benzene, loses H+ to
form nitrobenzene. =>
Chapter 17 7
 Sulfonation
Sulfur trioxide, SO3, in fuming sulfuric acid
is the electrophile.
_
O O O O
S S+ S+ S +
_ _
O O O O O O O O

_ HO
H O O
O S
S O O
S +
O O
O H
benzenesulfonic acid
=>
Chapter 17 8
 Desulfonation
• All steps are reversible, so sulfonic acid
group can be removed by heating in
dilute sulfuric acid.
• This process is used to place deuterium
in place of hydrogen on benzene ring.
H D

H H large excess D D
D2SO4/D2O

H H D D
=>
H D
Chapter 17 Benzene-d6 9
 Nitration of Toluene
• Toluene reacts 25 times faster than benzene.
The methyl group is an activator.
• The product mix contains mostly ortho and
para substituted molecules.

=>
Chapter 17 10
Sigma Complex
Intermediate
is more
stable if
nitration
occurs at
the ortho
or para
position.

Chapter 17
=>
11
Energy Diagram

Chapter 17
=>
12
 Activating, O-, P-
Directing Substituents
• Alkyl groups stabilize the sigma complex
by induction, donating electron density
through the sigma bond.
• Substituents with a lone pair of electrons
stabilize the sigma complex by resonance.
+
OCH3 OCH3
+
NO2 NO2
H =>
H Chapter 17 13
Nitration of Anisole

Ortho attack

Meta attack

Para attack

=>
Chapter 17 14
 The Amino Group
Aniline reacts with bromine water (without a
catalyst) to yield the tribromide. Sodium
bicarbonate is added to neutralize the
HBr that’s also formed.
NH2
NH2
Br Br
3 Br2
H2O, NaHCO3
Br =>
Chapter 17 15
Summary of
Activators

Chapter 17 16 =>
 Deactivating Meta-
Directing Substituents
• Electrophilic substitution reactions for
nitrobenzene are 100,000 times slower
than for benzene.
• The product mix contains mostly the
meta isomer, only small amounts of the
ortho and para isomers.
• Meta-directors deactivate all positions
on the ring, but the meta position is less
deactivated.
Chapter 17
=>17
Ortho Substitution
on Nitrobenzene

=>
Chapter 17 18
Para Substitution
on Nitrobenzene

=>
Chapter 17 19
Meta Substitution
on Nitrobenzene

=>
Chapter 17 20
Energy Diagram

=>
Chapter 17 21
 Structure of Meta-
Directing Deactivators

• The atom attached to the aromatic ring

will have a partial positive charge.
• Electron density is withdrawn
inductively along the sigma bond, so the
ring is less electron-rich than benzene.

=>
Chapter 17 22
Summary of Deactivators

=>
Chapter 17 23
More Deactivators

=>
Chapter 17 24
 Halobenzenes
• Halogens are deactivating toward
electrophilic substitution, but are ortho,
para-directing!
• Since halogens are very electronegative,
they withdraw electron density from the
ring inductively along the sigma bond.
• But halogens have lone pairs of electrons
that can stabilize the sigma complex by
resonance. =>
Chapter 17 25
 Sigma Complex
for Bromobenzene
Ortho attack Para attack

+
+ Br Br
Br Br (+)
+ (+) H
E
E (+) (+)
(+) (+)
E+ H E

Ortho and para attacks produce a bromonium ion

and other resonance structures.
Meta attack
Br
Br
(+)
H No bromonium ion
+
+
E
H
possible with meta attack.
(+) E

=>
Chapter 17 26
Energy Diagram

=>
Chapter 17 27
 Summary of
Directing Effects

Chapter 17 28
=>
 Multiple Substituents
The most strongly activating substituent
will determine the position of the next
substitution. May have mixtures.
OCH3 OCH3 OCH3
SO3H
SO3
+
H2SO4
O2N O 2N O2N
SO3H

=>
Chapter 17 29
Friedel-Crafts Alkylation
• Synthesis of alkyl benzenes from alkyl
halides and a Lewis acid, usually AlCl3.
• Reactions of alkyl halide with Lewis acid
produces a carbocation which is the
electrophile.
• Other sources of carbocations:
alkenes + HF or alcohols + BF3.
=>
Chapter 17 30
 Examples of
Carbocation Formation
Cl CH3 + _
CH3 CH CH3 + AlCl3 C Cl AlCl3
H3C H

_
F
HF +
H2C CH CH3 H3C CH CH3

+ BF3
H O
OH _
BF3 +
H3C CH CH3 H3C CH CH3 H3C CH CH3 + HOBF3
=>
Chapter 17 31
 Formation of
Alkyl Benzene
CH3 H
+C H CH(CH3)2
+
CH3 H

F
- CH3
H F B OH HF
F CH + F
+ CH(CH3)2 B OH
CH3
F
H
=>
Chapter 17 32
 Limitations of
Friedel-Crafts
• Reaction fails if benzene has a substituent
that is more deactivating than halogen.
• Carbocations rearrange. Reaction of
benzene with n-propyl chloride and AlCl3
produces isopropylbenzene.
• The alkylbenzene product is more reactive
than benzene, so polyalkylation occurs.
=>
Chapter 17 33
 Friedel-Crafts
Acylation
• Acyl chloride is used in place of alkyl
chloride.
• The acylium ion intermediate is
resonance stabilized and does not
rearrange like a carbocation.
• The product is a phenyl ketone that is
less reactive than benzene.
=>
Chapter 17 34
Mechanism of Acylation
O O
+ _
R C Cl AlCl3 R C Cl AlCl3

O
+ _ _ + +
R C Cl AlCl3 AlCl4 + R C O R C O

O
O O HCl
C R _
C+ Cl AlCl3 C R +
H AlCl3
R +
H

=>
Chapter 17 35
Clemmensen Reduction
Acylbenzenes can be converted to
alkylbenzenes by treatment with
aqueous HCl and amalgamated zinc.
O
O C CH2CH3 CH2CH2CH3
1) AlCl3
Zn(Hg)
+ CH3CH2C Cl
2) H2O aq. HCl

=>
Chapter 17 36
 Gatterman-Koch
Formylation
• Formyl chloride is unstable. Use a high
pressure mixture of CO, HCl, and catalyst.
• Product is benzaldehyde.
O _
AlCl3/CuCl +
CO + HCl H C Cl H C O AlCl4

O O

C+ C H
+ + HCl
H
=>
Chapter 17 37
 Nucleophilic
Aromatic Substitution
• A nucleophile replaces a leaving group
on the aromatic ring.
• Electron-withdrawing substituents
activate the ring for nucleophilic
substitution.

=>
Chapter 17 38
 Examples of
Nucleophilic Substitution

Chapter 17
=>
39
Addition-Elimination
Mechanism

=>
Chapter 17 40
 Benzyne Mechanism
• Reactant is halobenzene with no electron-
withdrawing groups on the ring.
• Use a very strong base like NaNH2.

Chapter 17
=> 41
 Benzyne Intermediate

_ NH2 NH2
NH2 NH2 _
H H H H
or
H H H H H H H H
CH3 CH3 CH3 CH3

meta-toluidine para-toluidine
=>
Chapter 17 42
Chlorination of Benzene
• Addition to the benzene ring may occur
with high heat and pressure (or light).
• The first Cl2 addition is difficult, but the
next 2 moles add rapidly.
• The product, benzene hexachloride, is
an insecticide.

=>
Chapter 17 43
 Catalytic Hydrogenation
• Elevated heat and pressure is required.
• Possible catalysts: Pt, Pd, Ni, Ru, Rh.
• Reduction cannot be stopped at an
intermediate stage.
CH3 CH3

3 H2, 1000 psi

Ru, 100°C
CH3 CH3 =>

Chapter 17 44
 Birch Reduction:
Regiospecific
• A carbon with an e--withdrawing group
O
is reduced. O
_
C
C O
OH Na, NH3 H
CH3CH2OH

• A carbon with an e--releasing group

is not reduced.
OCH3 OCH3
Li, NH3
(CH3)3COH, THF =>
Chapter 17 45
Birch Mechanism

=>
Chapter 17 46
 Side-Chain Oxidation
Alkylbenzenes are oxidized to benzoic
acid by hot KMnO4 or Na2Cr2O7/H2SO4.
_
CH(CH3)2 COO
-
KMnO4, OH
_
H2O, heat COO
CH CH2

=>
Chapter 17 47
 Side-Chain Halogenation
• Benzylic position is the most reactive.
• Chlorination is not as selective as
bromination, results in mixtures.
• Br2 reacts only at the benzylic position.
Br
CH2CH2CH3 CHCH2CH3
Br2, h

=>
Chapter 17 48
 SN1 Reactions
• Benzylic carbocations are resonance-
stabilized, easily formed.
• Benzyl halides undergo SN1 reactions.

CH3CH2OH, heat
CH2Br CH2OCH2CH3

=>
Chapter 17 49
 SN2 Reactions
• Benzylic halides are 100 times more
reactive than primary halides via SN2.
• Transition state is stabilized by ring.

=>
Chapter 17 50
 Reactions of Phenols
• Some reactions like aliphatic alcohols:
phenol + carboxylic acid  ester
phenol + aq. NaOH  phenoxide ion
• Oxidation to quinones: 1,4-diketones.
O
OH
Na2Cr2O7, H2SO4

CH3 CH3 =>

Chapter 17
O 51
 Quinones
• Hydroquinone is used as a developer
for film. It reacts with light-sensitized
AgBr grains, converting it to black Ag.
• Coenzyme Q is an oxidizing agent
found in the mitochondria of cells.

=>
Chapter 17 52
 Electrophilic
Substitution of Phenols
• Phenols and phenoxides are highly reactive.
• Only a weak catalyst (HF) required for
Friedel-Crafts reaction.
• Tribromination occurs without catalyst.
• Even reacts with CO2. _
_
O O O OH O
- C _ C
CO2, OH O +
H OH

=>
salicylic acid
Chapter 17 53
End of Chapter 17

Chapter 17 54