Transcript Reactions of Aromatic Compounds

Organic Chemistry, 7th Edition
L. G. Wade, Jr.
Chapter 17
Reactions of Aromatic Compounds
Copyright © 2010 Pearson Education, Inc.
Electrophilic Aromatic
Substitution
 Although benzene’s pi electrons are in a stable aromatic
system, they are available to attack a strong electrophile to give
a carbocation.
 This resonance-stabilized carbocation is called a sigma
complex because the electrophile is joined to the benzene ring
by a new sigma bond.
 Aromaticity is regained by loss of a proton.
Chapter 17
2
Mechanism of Electrophilic
Aromatic Substitution
Chapter 17
3
Bromination of Benzene
Chapter 17
4
Mechanism for the Bromination
of Benzene: Step 1
Br Br
FeBr3
Br
+
Br
FeBr3
(stronger electrophile than Br2)
 Before the electrophilic aromatic substitution can take
place, the electrophile must be activated.
 A strong Lewis acid catalyst, such as FeBr3, should
be used.
Chapter 17
5
Mechanism for the Bromination
of Benzene: Steps 2 and 3
Step 2: Electrophilic attack and formation of the sigma complex.
H
H
H
H
Br
H
H
H
Br
Br
FeBr3
H
H
H
+ FeBr4-
H
H
Step 3: Loss of a proton to give the products.
H
H
H
Br
H
FeBr4H
Br
+ FeBr3 + HBr
H
H
H
H
H
H
Chapter 17
6
Energy Diagram for Bromination
Chapter 17
7
Chlorination and Iodination
 Chlorination is similar to bromination.
AlCl3 is most often used as catalyst, but
FeCl3 will also work.
 Iodination requires an acidic oxidizing
agent, like nitric acid, to produce iodide
cation.
H+ + HNO3 + ½ I2
Chapter 17
I+ + NO2 + H2O
8
Solved Problem 1
Predict the major product(s) of bromination of p-chloroacetanilide.
Solution
The amide group (–NHCOCH3) is a strong activating and directing group because the nitrogen atom
with its nonbonding pair of electrons is bonded to the aromatic ring. The amide group is a stronger
director than the chlorine atom, and substitution occurs mostly at the positions ortho to the amide. Like
an alkoxyl group, the amide is a particularly strong activating group, and the reaction gives some of
the dibrominated product.
Chapter 17
9
Nitration of Benzene
NO2
HNO3
H2SO4
+
H2O
 Sulfuric acid acts as a catalyst, allowing the reaction
to be faster and at lower temperatures.
 HNO3 and H2SO4 react together to form the
electrophile of the reaction: nitronium ion (NO2+).
Chapter 17
10
Mechanism for the Nitration of
Benzene
Chapter 17
11
Reduction of the Nitro Group
NO2
NH2
Zn, Sn, or Fe
aq. HCl
 Treatment with zinc, tin, or iron in dilute acid
will reduce the nitro to an amino group.
 This is the best method for adding an amino
group to the ring.
Chapter 17
12
Sulfonation of Benzene
+
SO3
H2SO4
SO3H
 Sulfur trioxide (SO3) is the electrophile in the
reaction.
 A 7% mixture of SO3 and H2SO4 is commonly
referred to as “fuming sulfuric acid”.
 The —SO3H groups is called a sulfonic acid.
Chapter 17
13
Mechanism of Sulfonation
 Benzene attacks sulfur trioxide, forming a sigma
complex.
 Loss of a proton on the tetrahedral carbon and
reprotonation of oxygen gives benzenesulfonic acid.
Chapter 17
14
Desulfonation Reaction
SO3H
+
H , heat
H
+ H2O
+ H2SO4
 Sulfonation is reversible.
 The sulfonic acid group may be removed
from an aromatic ring by heating in dilute
sulfuric acid.
Chapter 17
15
Mechanism of Desulfonation
 In the desulfonation reaction, a proton adds
to the ring (the electrophile) and loss of sulfur
trioxide gives back benzene.
Chapter 17
16
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
17
Ortho and Para Substitution
 Ortho and para attacks are preferred because their
resonance structures include one tertiary carbocation.
Chapter 17
18
Energy Diagram
Chapter 17
19
Meta Substitution
 When substitution occurs at the meta position, the
positive charge is not delocalized onto the tertiary
carbon, and the methyl groups has a smaller effect
on the stability of the sigma complex.
Chapter 17
20
Alkyl Group Stabilization
CH2CH3
CH2CH3
CH2CH3
CH2CH3
Br
Br2
FeBr3
+
+
Br
o-bromo
(38%)
m-bromo
(< 1%)
Br
p-bromo
(62%)
 Alkyl groups are activating substituents and ortho,
para-directors.
 This effect is called the inductive effect because
alkyl groups can donate electron density to the ring
through the sigma bond, making them more active.
Chapter 17
21
Substituents with Nonbonding
Electrons
Resonance stabilization is provided by a pi bond between
the —OCH3 substituent and the ring.
Chapter 17
22
Meta Attack on Anisole
 Resonance forms show that the methoxy
group cannot stabilize the sigma complex in
the meta substitution.
Chapter 17
23
Bromination of Anisole
 A methoxy group is so strongly activating that
anisole is quickly tribrominated without a
catalyst.
Chapter 17
24
The Amino Group
 Aniline reacts with bromine water (without a
catalyst) to yield the tribromoaniline.
 Sodium bicarbonate is added to neutralize
the HBr that is also formed.
Chapter 17
25
Summary of Activators
Chapter 17
26
Activators and Deactivators
 If the substituent on the ring is electron donating, the
ortho and para positions will be activated.
 If the group is electron withdrawing, the ortho and
para positions will be deactivated.
Chapter 17
27
Nitration of Nitrobenzene
 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.
Chapter 17
28
Ortho Substitution on
Nitrobenzene
 The nitro group is a strongly deactivating group when
considering its resonance forms. The nitrogen
always has a formal positive charge.
 Ortho or para addition will create an especially
unstable intermediate.
Chapter 17
29
Meta Substitution on
Nitrobenzene
 Meta substitution will not put the positive
charge on the same carbon that bears the
nitro group.
Chapter 17
30
Energy Diagram
Chapter 17
31
Deactivators and MetaDirectors
 Most electron withdrawing groups are
deactivators and meta-directors.
 The atom attached to the aromatic ring has a
positive or partial positive charge.
 Electron density is withdrawn inductively
along the sigma bond, so the ring has less
electron density than benzene and thus, it will
be slower to react.
Chapter 17
32
Ortho Attack of Acetophenone
 In ortho and para substitution of acetophenone, one
of the carbon atoms bearing the positive charge is
the carbon attached to the partial positive carbonyl
carbon.
 Since like charges repel, this close proximity of the
two positive charges is especially unstable.
Chapter 17
33
Meta Attack on Acetophenone
 The meta attack on acetophenone avoids
bearing the positive charge on the carbon
attached to the partial positive carbonyl.
Chapter 17
34
Other Deactivators
Chapter 17
35
Nitration of Chlorobenzene
 When chlorobenzene is nitrated the main substitution
products are ortho and para. The meta substitution
product is only obtained in 1% yield.
Chapter 17
36
Halogens Are Deactivators
X
 Inductive Effect: Halogens are deactivating
because they are electronegative and can
withdraw electron density from the ring along
the sigma bond.
Chapter 17
37
Halogens Are Ortho, ParaDirectors
 Resonance Effect: The lone pairs on the
halogen can be used to stabilize the sigma
complex by resonance.
Chapter 17
38
Energy Diagram
Chapter 17
39
Summary of Directing Effects
Chapter 17
40
Effect of Multiple Substituents
 The directing effect of the two (or more)
groups may reinforce each other.
Chapter 17
41
Effect of Multiple Substituents
(Continued)
 The position in between two groups in
Positions 1 and 3 is hindered for substitution,
and it is less reactive.
Chapter 17
42
Effect of Multiple Substituents
(Continued)
OCH3
OCH3
OCH3
Br
Br2
FeBr3
O2N
O2N
O2N
Br
major products obtained
 If directing effects oppose each other, the
most powerful activating group has the
dominant influence.
Chapter 17
43
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.
Chapter 17
44
Mechanism of the Friedel–Crafts
Reaction
Step 1
Step 2
Step 3
Chapter 17
45
Protonation of Alkenes
 An alkene can be protonated by HF.
 This weak acid is preferred because the
fluoride ion is a weak nucleophile and will not
attack the carbocation.
Chapter 17
46
Alcohols and Lewis Acids
 Alcohols can be treated with BF3 to form the
carbocation.
Chapter 17
47
Limitations of Friedel–Crafts
 Reaction fails if benzene has a substituent
that is more deactivating than halogens.
 Rearrangements are possible.
 The alkylbenzene product is more reactive
than benzene, so polyalkylation occurs.
Chapter 17
48
Rearrangements
Chapter 17
49
Solved Problem 2
Devise a synthesis of p-nitro-t-butylbenzene from benzene.
Solution
To make p-nitro-t-butylbenzene, we would first use a Friedel–Crafts reaction to make t-butylbenzene.
Nitration gives the correct product. If we were to make nitrobenzene first, the Friedel–Crafts reaction
to add the t-butyl group would fail.
Chapter 17
50
Friedel–Crafts Acylation
 Acyl chloride is used in place of alkyl chloride.
 The product is a phenyl ketone that is less
reactive than benzene.
Chapter 17
51
Mechanism of Acylation
Step 1: Formation of the acylium ion.
Step 2: Electrophilic attack to form the sigma complex.
Chapter 17
52
Clemmensen Reduction
 The Clemmensen reduction is a way to
convert acylbenzenes to alkylbenzenes by
treatment with aqueous HCl and
amalgamated zinc.
Chapter 17
53
Nucleophilic Aromatic
Substitution
 A nucleophile replaces a leaving group on the
aromatic ring.
 This is an addition–elimination reaction.
 Electron-withdrawing substituents activate the
ring for nucleophilic substitution.
Chapter 17
54
Mechanism of Nucleophilic
Aromatic Substitution
Step 1: Attack by hydroxide gives a resonance-stabilized complex.
Step 2: Loss of chloride gives the product. Step 3: Excess base deprotonates the product.
Chapter 17
55
Activated Positions
 Nitro groups ortho and para to the halogen
stabilize the intermediate (and the transition
state leading to it).
 Electron-withdrawing groups are essential for
the reaction to occur.
Chapter 17
56
Benzyne Reaction: EliminationAddition
 Reactant is halobenzene with no electronwithdrawing groups on the ring.
 Use a very strong base like NaNH2.
Chapter 17
57
Benzyne Mechanism
 Sodium amide abstract a proton.
 The benzyne intermediate forms when the bromide is
expelled and the electrons on the sp2 orbital adjacent
to it overlap with the empty sp2 orbital of the carbon
that lost the bromide.
 Benzynes are very reactive species due to the high
strain of the triple bond.
Chapter 17
58
Nucleophilic Substitution on the
Benzyne Intermediate
Chapter 17
59
Chlorination of Benzene
 Addition to the
benzene ring may
occur with excess of
chlorine under heat
and pressure.
 The first Cl2 addition is
difficult, but the next
two moles add rapidly.
Chapter 17
An insecticide
60
Catalytic Hydrogenation
CH 3
CH 3
3 H 2, 1000 psi
Ru, 100°C
CH 3
CH 3
 Elevated heat and pressure is required.
 Possible catalysts: Pt, Pd, Ni, Ru, Rh.
 Reduction cannot be stopped at an
intermediate stage.
Chapter 17
61
Birch Reduction
H
H
H
H
Na or Li
NH3 (l), ROH
H
H
H
H
H
H
H
H
H
H
 This reaction reduces the aromatic ring to a
nonconjugated 1,4-cyclohexadiene.
 The reducing agent is sodium or lithium in a
mixture of liquid ammonia and alcohol.
Chapter 17
62
Mechanism of the Birch Reduction
Chapter 17
63
Limitations of the Birch Reduction
Chapter 17
64
Side-Chain Oxidation
CH2CH3
KMnO4, NaOH
H2O, 100oC
CO2H
(or Na2Cr2O7, H2SO4 , heat)
 Alkylbenzenes are oxidized to benzoic acid by
heating in basic KMnO4 or heating in
Na2Cr2O7/H2SO4.
 The benzylic carbon will be oxidized to the carboxylic
acid.
Chapter 17
65
Side-Chain Halogenation
Br
CH2CH3
Br2 or NBS
h
CHCH3
 The benzylic position is the most reactive.
 Br2 reacts only at the benzylic position.
 Cl2 is not as selective as bromination, so
results in mixtures.
Chapter 17
66
Mechanism of Side-Chain
Halogenation
Chapter 17
67
SN1 Reactions
 Benzylic carbocations are resonancestabilized, easily formed.
 Benzyl halides undergo SN1 reactions.
CH 2Br
C H 3 CH 2 O H, heat
Chapter 17
C H 2 O CH 2C H 3
68
SN2 Reactions
 Benzylic halides are
100 times more
reactive than
primary halides via
SN2.
 The transition state
is stabilized by a
ring.
Chapter 17
69
Oxidation of Phenols
OH
O
Cl
Cl
Na2Cr2O7
H2SO4
O
2-chloro-1,4-benzoquinone
 Phenol will react with oxidizing agents to produce
quinones.
 Quinones are conjugated 1,4-diketones.
 This can also happen (slowly) in the presence of air.
Chapter 17
70