Organic Chemistry 7e by Wade

1. Chapter 17
Copyright © 2010 Pearson Education, Inc.
Organic Chemistry, 7th
Edition
L. G. Wade, Jr.
Reactions of Aromatic Compounds

2. Chapter 17 2
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.

3. Chapter 17 3
Mechanism of Electrophilic
Aromatic Substitution

4. Chapter 17 4
Bromination of Benzene

5. Chapter 17 5
Mechanism for the
Bromination of Benzene: Step
1
 Before the electrophilic aromatic substitution can take
place, the electrophile must be activated.
 A strong Lewis acid catalyst, such as FeBr3, should
be used.
Br Br FeBr3 Br Br FeBr3
+ -
(stronger electrophile than Br2)

6. Chapter 17 6
H
H
H
H
H
H
Br Br FeBr3
H
H
H
H
H
H
Br
+ FeBr4
-
H
H
H
H
H
H
Br
FeBr4
-
Br
H
H
H
H
H
+ FeBr3 + HBr
Step 2: Electrophilic attack and formation of the sigma complex.
Step 3: Loss of a proton to give the products.
Mechanism for the
Bromination of Benzene: Steps
2 and 3

7. Chapter 17 7
Energy Diagram for Bromination

8. Chapter 17 8
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 I+
+ NO2 + H2O

9. Chapter 17 9
Predict the major product(s) of bromination of p-chloroacetanilide.
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.
Solved Problem 1
Solution

10. Chapter 17 10
Nitration of Benzene
 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
+
).
HNO3
H2SO4
NO2
+ H2O

11. Chapter 17 11
Mechanism for the Nitration of
Benzene

12. Chapter 17 12
Reduction of the Nitro Group
NO2
Zn, Sn, or Fe
aq. HCl
NH2
 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.

13. Chapter 17 13
Sulfonation of Benzene
 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.
SO3H
+ SO3
H2SO4

14. Chapter 17 14
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.

15. Chapter 17 15
Desulfonation Reaction
 Sulfonation is reversible.
 The sulfonic acid group may be removed
from an aromatic ring by heating in dilute
sulfuric acid.
HSO3H
+ H2O
H+
, heat
+ H2SO4

16. Chapter 17 16
Mechanism of Desulfonation
 In the desulfonation reaction, a proton adds
to the ring (the electrophile) and loss of sulfur
trioxide gives back benzene.

17. Chapter 17 17
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.

18. Chapter 17 18
Ortho and Para Substitution
 Ortho and para attacks are preferred because their
resonance structures include one tertiary carbocation.

19. Chapter 17 19
Energy Diagram

20. Chapter 17 20
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.

21. Chapter 17 21
Alkyl Group Stabilization
CH2CH3
Br2
FeBr3
CH2CH3
Br
CH2CH3
Br
CH2CH3
Br
+ +
o-bromo
(38%)
m-bromo
(< 1%)
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.

22. Chapter 17 22
Substituents with Nonbonding
Electrons
Resonance stabilization is provided by a pi bond between
the —OCH3 substituent and the ring.

23. Chapter 17 23
Meta Attack on Anisole
 Resonance forms show that the methoxy
group cannot stabilize the sigma complex in
the meta substitution.

24. Chapter 17 24
Bromination of Anisole
 A methoxy group is so strongly activating that
anisole is quickly tribrominated without a
catalyst.

25. Chapter 17 25
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.

26. Chapter 17 26
Summary of Activators

27. Chapter 17 27
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.

28. Chapter 17 28
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.

29. Chapter 17 29
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.

30. Chapter 17 30
Meta Substitution on
Nitrobenzene
 Meta substitution will not put the positive
charge on the same carbon that bears the
nitro group.

31. Chapter 17 31
Energy Diagram

32. Chapter 17 32
Deactivators and Meta-
Directors
 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.

33. Chapter 17 33
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.

34. Chapter 17 34
Meta Attack on Acetophenone
 The meta attack on acetophenone avoids
bearing the positive charge on the carbon
attached to the partial positive carbonyl.

35. Chapter 17 35
Other Deactivators

36. Chapter 17 36
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.

37. Chapter 17 37
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.

38. Chapter 17 38
Halogens Are Ortho, Para-
Directors
 Resonance Effect: The lone pairs on the
halogen can be used to stabilize the sigma
complex by resonance.

39. Chapter 17 39
Energy Diagram

40. Chapter 17 40
Summary of Directing Effects

41. Chapter 17 41
Effect of Multiple Substituents
 The directing effect of the two (or more)
groups may reinforce each other.

42. Chapter 17 42
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.

43. Chapter 17 43
Effect of Multiple Substituents
(Continued)
OCH3
O2N
Br2
FeBr3
OCH3
O2N
Br
OCH3
O2N
Br
 If directing effects oppose each other, the
most powerful activating group has the
dominant influence.
major products obtained

44. Chapter 17 44
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.

45. Chapter 17 45
Mechanism of the Friedel–Crafts
Reaction
Step 1
Step 2
Step 3

46. Chapter 17 46
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.

47. Chapter 17 47
Alcohols and Lewis Acids
 Alcohols can be treated with BF3 to form the
carbocation.

48. Chapter 17 48
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.

49. Chapter 17 49
Rearrangements

50. Chapter 17 50
Devise a synthesis of p-nitro-t-butylbenzene from benzene.
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.
Solved Problem 2
Solution

51. Chapter 17 51
Friedel–Crafts Acylation
 Acyl chloride is used in place of alkyl chloride.
 The product is a phenyl ketone that is less
reactive than benzene.

52. Chapter 17 52
Mechanism of Acylation
Step 1: Formation of the acylium ion.
Step 2: Electrophilic attack to form the sigma complex.

53. Chapter 17 53
Clemmensen Reduction
 The Clemmensen reduction is a way to
convert acylbenzenes to alkylbenzenes by
treatment with aqueous HCl and
amalgamated zinc.

54. Chapter 17 54
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.

55. Chapter 17 55
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.

56. Chapter 17 56
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.

57. Chapter 17 57
Benzyne Reaction: Elimination-
Addition
 Reactant is halobenzene with no electron-
withdrawing groups on the ring.
 Use a very strong base like NaNH2.

58. Chapter 17 58
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.

59. Chapter 17 59
Nucleophilic Substitution on the
Benzyne Intermediate

60. Chapter 17 60
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. An insecticide

61. Chapter 17 61
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
Ru, 100°C
1000 psi3H2,
CH3
CH3

62. Chapter 17 62
Birch Reduction
H
H
H
H
H
H
Na or Li
NH3 (l), ROH
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.

63. Chapter 17 63
Mechanism of the Birch Reduction

64. Chapter 17 64
Limitations of the Birch Reduction

65. Chapter 17 65
Side-Chain Oxidation
 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.
CH2CH3
(or Na2Cr2O7, H2SO4 , heat)
CO2H
KMnO4, NaOH
H2O, 100oC

66. Chapter 17 66
Side-Chain Halogenation
CH2CH3
Br2 or NBS
hν
CHCH3
Br
 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.

67. Chapter 17 67
Mechanism of Side-Chain
Halogenation

68. Chapter 17 68
SN1 Reactions
 Benzylic carbocations are resonance-
stabilized, easily formed.
 Benzyl halides undergo SN1 reactions.
CH2Br
CH3CH2OH, heat
CH2OCH2CH3

69. Chapter 17 69
SN2 Reactions
 Benzylic halides are
100 times more
reactive than
primary halides via
SN2.
 The transition state
is stabilized by a
ring.

70. Chapter 17 70
Oxidation of Phenols
Na2Cr2O7
H2SO4
OH
Cl
O
Cl
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.