CHE 242
Unit VI
The Study of Conjugated
Systems, Aromaticity and
Reactions of Aromatic
Compounds
CHAPTER SEVENTEEN
Terrence P. Sherlock
Burlington County College
2004
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
H
Br
Animation
H
H
H
H
FeBr3
H
H
H
Br
Br
FeBr3
+
H
H
_
+ FeBr4
Animation
H
H
Animation
Br
+
Chapter 17
HBr
=>
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
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
_
+ HSO4
NO2+ then forms a
sigma complex with
benzene, loses H+ to
form nitrobenzene. =>
7
Sulfonation
Sulfur trioxide, SO3, in fuming sulfuric acid
is the electrophile.
O
_
O
O
S
S+
O
O
O
O
O
S+
_
O
O
_
O
S
O
O
H O
S O
+
O
H
_
S +
O
O
HO
O
S
O
benzenesulfonic acid
=>
Chapter 17
8
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
9
Sigma Complex
Intermediate
is more
stable if
nitration
occurs at
the ortho
or para
position.
Chapter 17
=>
10
Energy Diagram
Chapter 17
=>
11
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
NO2
NO2
+
H
H
Chapter 17
=>
12
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
=>
13
Summary of
Activators
Chapter 17
14
=>
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.
=>
Chapter 17
15
Ortho Substitution
on Nitrobenzene
=>
Chapter 17
16
Para Substitution
on Nitrobenzene
=>
Chapter 17
17
Meta Substitution
on Nitrobenzene
=>
Chapter 17
18
Energy Diagram
=>
Chapter 17
19
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
20
Summary of Deactivators
=>
Chapter 17
21
More Deactivators
=>
Chapter 17
22
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
23
Sigma Complex
for Bromobenzene
Para attack
Ortho attack
Br
Br
+
(+)
+
E
Br
Br
(+)
H
E
(+)
+
(+)
(+)
+
E
(+)
H E
Ortho and para attacks produce a bromonium ion
and other resonance structures.
Meta attack
Br
Br
H
(+)
+
+
H
E
(+)
No bromonium ion
possible with meta attack.
E
=>
Chapter 17
24
Multiple Substituents
The most strongly activating substituent
will determine the position of the next
substitution. May have mixtures.
OCH3
OCH3
SO3H
SO3
O2N
H2SO4
OCH3
+
O2N
O2N
SO3H
=>
Chapter 17
25
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
26
Examples of
Carbocation Formation
Cl
CH3
CH CH3
_
CH3 +
C Cl AlCl3
H3C H
+ AlCl3
_
H2C CH CH3
OH
H3C CH CH3
BF3
F
HF
+
H3C CH CH3
+ BF3
H O
H3C CH CH3
Chapter 17
_
+
H3C CH CH3 + HOBF3
=>
27
Formation of
Alkyl Benzene
CH3
H
+C H
+
CH3
H
F
H
+
CH(CH3)2
CH(CH3)2
F
-
B OH
CH3
F
CH
+
CH3
H
HF
F
B OH
F
=>
Chapter 17
28
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
29
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
30
Clemmensen Reduction
Acylbenzenes can be converted to
alkylbenzenes by treatment with
aqueous HCl and amalgamated zinc.
O
O
+ CH3CH2C Cl
1) AlCl3
C CH2CH3
2) H2O
Zn(Hg)
CH2CH2CH3
aq. HCl
=>
Chapter 17
31
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
+
AlCl3/CuCl
O
O
C+
C H
_
+
H C O AlCl4
+
HCl
H
Chapter 17
32
=>
Benzyne Mechanism
• Reactant is halobenzene with no electronwithdrawing groups on the ring.
• Use a very strong base like NaNH2.
Chapter 17
=> 33
Benzyne Intermediate
NH2
H
NH2
NH2
_
NH2
H
H
H
_
or
H
H
CH3
H
H
H
CH3
H
CH3
H
H
CH3
para-toluidine
meta-toluidine
Chapter 17
=>
34
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
35
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
Chapter 17
CH3 =>
36
Side-Chain Oxidation
Alkylbenzenes are oxidized to benzoic
acid by hot KMnO4 or Na2Cr2O7/H2SO4.
CH(CH3)2
-
KMnO4, OH
CH CH2
H2O, heat
_
COO
_
COO
=>
Chapter 17
37
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
Br2, h
CHCH2CH3
=>
Chapter 17
38
SN1 Reactions
• Benzylic carbocations are resonancestabilized, easily formed.
• Benzyl halides undergo SN1 reactions.
CH2Br
CH3CH2OH, heat
CH2OCH2CH3
=>
Chapter 17
39
SN2 Reactions
• Benzylic halides are 100 times more
reactive than primary halides via SN2.
• Transition state is stabilized by ring.
=>
Chapter 17
40
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
41
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
-
CO2, OH
O
C
OH
O
_
+
O
C
H
OH
=>
Chapter 17
salicylic acid
42
POWER POINT IMAGES FROM
“ORGANIC CHEMISTRY, 5TH EDITION”
L.G. WADE
ALL MATERIALS USED WITH PERMISSION OF AUTHOR
PRESENTATION ADAPTED FOR BURLINGTON COUNTY COLLEGE
ORGANIC CHEMISTRY COURSE
BY:
ANNALICIA POEHLER STEFANIE LAYMAN
CALY MARTIN
Chapter 17
43