Download Reactions of Aromatic Compounds

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
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
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
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-, 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
=>
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 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
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 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
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
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
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
SO3H
SO3
O2N
H2SO4
OCH3
+
O2N
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
CH CH3
_
CH3 +
C Cl AlCl3
H3C H
+ AlCl3
_
H2C CH CH3
OH
H3C CH CH3
BF3
F
+
H3C CH CH3
HF
+ BF3
H O
H3C CH CH3
Chapter 17
_
+
H3C CH CH3 + HOBF3
=>
31
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
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
R C Cl
O
+ _
R C Cl AlCl3
AlCl3
O
+ _
R C Cl AlCl3
_
AlCl4
+
+
R C O
O
O
C
C+
R
+
H
R
Cl
_
AlCl3
+
R C O
O
C
HCl
R +
AlCl3
H
=>
Chapter 17
35
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
36
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
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 electronwithdrawing groups on the ring.
• Use a very strong base like NaNH2.
Chapter 17
=> 41
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
=>
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
Chapter 17
CH3
=>
44
Birch Reduction:
Regiospecific
• A carbon with an e--withdrawing group
O
O
is reduced.
C
C
OH
Na, NH3
_
O
H
CH3CH2OH
• A carbon with an e--releasing group
is not reduced.
OCH3
Li, NH3
(CH3)3COH, THF
Chapter 17
OCH3
=>
45
Birch Mechanism
=>
Chapter 17
46
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
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
Br2, h
CHCH2CH3
=>
Chapter 17
48
SN1 Reactions
• Benzylic carbocations are resonancestabilized, easily formed.
• Benzyl halides undergo SN1 reactions.
CH2Br
CH3CH2OH, heat
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
-
CO2, OH
O
C
OH
O
_
+
O
C
H
OH
=>
Chapter 17
salicylic acid
53
End of Chapter 17
Chapter 17
54