Organic Chemistry, 6th Edition
L. G. Wade, Jr.
Chapter 17
Reactions of
Aromatic Compounds
Jo Blackburn
Richland College, Dallas, TX
Dallas County Community College District
 2006, Prentice Hall
Electrophilic
Aromatic Substitution
Electrophile substitutes for a hydrogen on
the benzene ring.
=>
Chapter 17
2
1
Mechanism
Step 1: Attack on the electrophile forms the sigma complex.
Step 2: Loss of a proton gives the substitution product.
=>
Chapter 17
3
Bromination of Benzene
• Requires a stronger electrophile than Br2.
• Use a strong Lewis acid catalyst, FeBr3.
Br Br
FeBr3
H
+
Br
H
Br
FeBr3
H
H
H
+
Br
H
Br
-
H
H
Br
FeBr3
+
H
_
+ FeBr4
H
H
H
Br
+
Chapter 17
HBr
=>
4
2
Comparison with Alkenes
• Cyclohexene adds Br2, ∆H = -121 kJ
• Addition to benzene is endothermic, not
normally seen.
• Substitution of Br for H retains
aromaticity, ∆H = -45 kJ.
• Formation of sigma complex is ratelimiting.
=>
Chapter 17
5
Energy Diagram
for Bromination
=>
Chapter 17
6
3
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
+
+ HNO 3 + 1/2 I2
I
+
NO2 + H2O
=>
Chapter 17
7
Nitration of Benzene
Use sulfuric acid with nitric acid to form
the nitronium ion electrophile.
O
H O
S
O H
O
H O
H O N
H O N
+
O
O
O
H O
H O N
+
O
O
H2O +
N+
O
Chapter 17
_
+ HSO 4
NO2+ then forms a
sigma complex with
benzene, loses H+ to
form nitrobenzene. =>
8
4
Sulfonation
Sulfur trioxide, SO3, in fuming sulfuric
acid is the electrophile.
O
_
O
O
S
S+
O
O
O
O
O
O
O
S +
O
HO
O
S
+
O
_
_
H
S
O
S+
_
O
O
H
O
S
O
O
O
benzenesulfonic acid
=>
Chapter 17
9
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.
D
H
H
H
H
H
H
large excess
D2SO4/D2O
D
D
D
D
=>
D
Chapter 17
Benzene-d6
10
5
Nitration of Toluene
• Toluene reacts 25 times faster than benzene.
The methyl group is an activating group.
• The product mix contains mostly ortho and
para substituted molecules.
=>
Chapter 17
11
Sigma Complex
Intermediate
is more
stable if
nitration
occurs at
the ortho
or para
position.
=>
Chapter 17
12
6
Energy Diagram
=>
13
Chapter 17
Activating, O-, PDirecting 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
NO 2
NO2
+
H
H
Chapter 17
=>
14
7
Substitution on Anisole
Chapter 17
=>
15
The Amino Group
Aniline, like anisole, reacts with bromine
water (without a catalyst) to yield the
tribromide. Sodium bicarbonate is added
to neutralize the HBr that’s also formed.
=>
Chapter 17
16
8
Summary of
Activators
Chapter 17
=>
17
Deactivating MetaDirecting 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.
=>18
Chapter 17
9
Ortho Substitution
on Nitrobenzene
=>
Chapter 17
19
Para Substitution
on Nitrobenzene
=>
Chapter 17
20
10
Meta Substitution
on Nitrobenzene
=>
Chapter 17
21
Energy Diagram
=>
Chapter 17
22
11
Structure of MetaDirecting 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
23
Summary of Deactivators
=>
Chapter 17
24
12
More Deactivators
=>
Chapter 17
25
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
26
13
Sigma Complex
for Bromobenzene
Ortho and para attacks produce a bromonium ion
and other resonance structures.
No bromonium ion
possible with meta attack.
=>
Chapter 17
27
Energy Diagram
=>
Chapter 17
28
14
Summary of
Directing Effects
Chapter 17
29
=>
Multiple Substituents
The most strongly activating substituent
will determine the position of the next
substitution. May have mixtures.
OCH3
OCH3
SO3H
SO3
O 2N
H2SO4
OCH3
+
O 2N
O 2N
SO3H
=>
Chapter 17
30
15
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
31
Examples of
Carbocation Formation
Cl
CH3
CH CH3
H2C
OH
H3C
CH CH3
CH CH3
BF3
_
CH3 +
C Cl AlCl3
H3C H
+ AlCl3
_
F
+
H3C CH CH3
HF
+ BF3
H O
H3C
CH CH3
Chapter 17
H3C
_
+
CH CH3 + HOBF3
=>
32
16
Formation of
Alkyl Benzene
CH3
+C
H
H
+
CH3
H
F
F
H
+
CH(CH3)2
CH(CH3)2
-
B OH
CH3
F
CH
+
CH3
H
HF
F
B OH
F
=>
Chapter 17
33
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
34
17
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
35
Mechanism of Acylation
O
O
C
C+
R
+
H
R
Cl
_
AlCl3
O
C
HCl
R +
AlCl3
H
Chapter 17
=>
36
18
Clemmensen Reduction
Acylbenzenes can be converted to
alkylbenzenes by treatment with
aqueous HCl and amalgamated zinc.
O
O
+ CH3CH2C Cl
C CH2CH3
1) AlCl3
2) H2O
CH2CH2CH3
Zn(Hg)
aq. HCl
=>
Chapter 17
37
Gatterman-Koch
Formylation
• Formyl chloride is unstable. Use a high
pressure mixture of CO, HCl, and catalyst.
• Product is benzaldehyde.
O
H C Cl
CO + HCl
+
_
+
H C O AlCl4
AlCl3/CuCl
O
O
C+
C
H
+
HCl
H
Chapter 17
38
=>
19
Nucleophilic
Aromatic Substitution
• A nucleophile replaces a leaving group
on the aromatic ring.
• Electron-withdrawing substituents
activate the ring for nucleophilic
substitution.
=>
Chapter 17
39
Examples of
Nucleophilic Substitution
Chapter 17
=>
40
20
Addition-Elimination
Mechanism
Chapter 17
=>
41
21