CH 16: Chemistry of Benzene

Renee Y. Becker
CHM 2211
Valencia Community College

1
 Substitution Reactions of Benzene and Its Derivatives

Benzene does not undergo electrophilic

addition

It undergoes electrophilic aromatic

substitution maintaining the aromatic core

Electrophilic aromatic substitution replaces

a proton on benzene with another
electrophile

2
electrophilic aromatic substitution

3
Electrophilic Aromatic Substitution

4
 Halogenation of Benzene

Benzenes electrons participate as a Lewis

base in reactions with Lewis acids

Lewis acid: electron pair acceptor

Lewis base: electron pair donor

The product is formed by loss of a proton, which

is replaced by a halogen

5
 Bromination of Aromatic Rings

Benzenes electrons participate as a Lewis

base in reactions with Lewis acids
The product is formed by loss of a proton, which
is replaced by bromine
FeBr3 is added as a catalyst to polarize the
bromine reagent

Br
FeBr3
+ Br2 + HBr

6
Bromine Polarization

7
 Mechanism 1

Diagram the mechanism for the bromination of

benzene and note the formation of the
carbocation:

8
 Example 1

Draw and name the three possible

products of the bromination of toluene (not
including HBr).

9
 Chlorination of Aromatic Rings

Cl
FeCl3
+ Cl2 + HCl

Same mechanism as Br2 with FeBr3

10
 Iodination of Aromatic Rings

I2 I
+ HI
CuCl2

Iodine is unreactive towards aromatic rings

Oxidizing agents must be added to make
reaction go (H2O2 or CuCl2)
Oxidizing agents oxidize I2 to a usable form
(electrohphillic) that reacts as if it were I+
11
 Mechanism 2: Iodination of Aromatic Rings

I2 + 2 Cu2+ 2 I+ + 2 Cu+

I
I2 +
+ I+ H I
CuCl2

I
+ HI

12
 Nitration of Aromatic Rings

HNO3 NO2
H2O
H2SO4

Electrophile is the nitronium ion (NO2+)

Generated from HNO3 by protonation and
loss of water
13
 Mechanism 3: Nitration of Aromatic Rings

An electrophile must first be generated by

treating concentrated nitric acid with
concentrated sulfuric acid

H
H O NO2 + H2SO4 H O NO2 + HSO4

NO2 H2O
nitronium ion 14
 Mechanism 3: Nitration of Aromatic Rings

The nitronium electrophile is attacked by the

benzene ring (nucleophile)

NO2+ NO2 NO2

H2SO4

15
 Sulfonation of Aromatic Rings

SO2OH
SO3
+ H2O
H2SO4

Fuming sulfuric acid combination of SO3 and H2SO4

Electrophile is HSO3+ or SO3
Reaction is reversible
Favored in forward direction with strong acid
Favored in reverse direction with hot dilute
aqueous acid
16
 Mechanism 4: Sulfonation of Aromatic Rings

H
O O
+ O O
S + H O S OH
S
+ + O S OH
O O
O O O
O

H O
O
O S OH
+ +
S H
O O
+
O
O S OH
O

SO3H
+ H2SO4

17
 Conversion of sulfonic acids

Heating with NaOH at 300 C followed by

neutralization with acid replaces the SO3H group
with an OH

SO3H 1. NaOH, 300o OH

2.H3O

No mechanism
18
 Friedel-Crafts Reaction

CH3
Cl CHCH3
+ CH CHCH AlCl3 + HCl
3 3

benzene 2-chloropropane isopropylbenzene

19
 Mechanism 5: Friedel-Crafts Reaction

Cl AlCl 3

+ + HCl

Cl AlCl3
+ +
+ Cl--AlCl3 -

+
+ H
+
Cl--AlCl3-

+ HCl + AlCl3
20
 Friedel-Crafts Reaction (Alkylation of Aromatic Rings)

the electrophile is a carbocation, R+

only alkyl halides can be used

aryl halides and vinylic halides do not react.

will not occur on aromatic rings substituted by

electron withdrawing substituents

cant eat just one! Its hard to stop after one

substitution

skeletal rearrangements of the alkyl group often

occur when using primary alkyl halides
21
Non-reactive

22
Ring Deactivators

23
 Example 2: Friedel-Crafts Reaction

Diagram the mechanism for the electrophilic

substitution of benzene by 2-chloropentane:

24
 Friedel-Crafts Reaction

Multiple substitutions:
Reaction of benzene with 2-chloro-
2methylpropane.
Polyalkylation

C(CH3)3 C(CH3)3
Cl
+ CH CCH AlCl3 + HCl
3 3
CH3
C(CH3)3
Major
product
25
 Friedel-Crafts Reaction

Skeletal rearrangements in Friedel-Crafts

reactions (hydride shift):
Will rearrange to form more stable carbocation
intermediates
Major
product CH3
CHCH2CH3
CH3CH2CH2CH2Cl
AlCl3
sec-Butylbenzene HCl
+
CH2CH2CH2CH3

Butylbenzene 26
 Friedel-Crafts Reaction

Skeletal rearrangements in Friedel-Crafts

reactions (alkyl shift):
Will rearrange to form more stable carbocation
intermediates

AlCl3
+ Cl
HCl

1-Chloro-2,2- (1,1-Dimethylpropyl)-
dimethylpropane benzene

27
 Example 3:

Which of the following alkyl halides would you

expect to undergo Friedel-Crafts reaction
without rearrangement?
Chloroethane
2-chlorobutane
1-chloropropane
1-chloro-2,2-dimethylpropane
Chlorocyclohexane
28
 Friedel-Crafts Alkylation Summary

Only alkyl halides can be used!!

Will not occur on aromatic rings substituted by
electron withdrawing substituents
Carbonyl and amino groups

Will have polyalkylation

Will have rearrangement to form more stable
carbocation intermediate
Hydride shift or methyl shift
You need to know the mechanism!!!
29
 Friedel-Crafts Acylation

Reaction of benzene with a carboxylic acid

chloride, RCOCl in the presence of AlCl3

Note: the acyl cation does not undergo

rearrangement. It also is not prone to multiple
substitutions.
O
O C
AlCl3 CH2CH3
+ CH3CH2CCl
HCl

30
 Friedel-Crafts Acylation

After acylation we can do a hydrogenation to get

desired alkylated product

AlCl3
HCl

H2
Pd

31
 Mechanism 6: Friedel-Crafts Acylation

Acyl cation
Cl AlCl3
+ H3C C+
CH3 C O+
O O + Cl--AlCl3-

H3C C+
+ O H
+
Cl--AlCl3-

+ HCl + AlCl 3

32
 Substituent Effects in Aromatic Rings

Substituents can cause a compound to be

(much) more or (much) less reactive than
benzene

Substituents affect the orientation of the

reaction the positional relationship is
controlled

ortho- and para-directing activators, ortho-

and para-directing deactivators, and meta-
directing deactivators
33
34
35
 Origins of Substituent Effects

An interplay of inductive effects and resonance

effects

Inductive effect - withdrawal or donation of

electrons through a s bond (comparative
electronegativity)

Resonance effect - withdrawal or donation of

electrons through a bond due to the overlap of
a p orbital on the substituent with a p orbital on
the aromatic ring 36
 Inductive Effects

Controlled by electronegativity and the polarity

of bonds in functional groups

Halogens, C=O, CN, and NO2 withdraw

electrons through s bond connected to ring

Alkyl groups donate electrons

37
38
 Resonance Effects Electron Withdrawal

C=O, CN, NO2 substituents withdraw electrons

from the aromatic ring by resonance

electrons flow from the rings to the

substituents

39
 Resonance Effects Electron Donation

Halogen, OH, alkoxyl (OR), and amino

substituents donate electrons
electrons flow from the substituents to the ring
Effect is greatest at ortho and para

40
 Contrasting Effects

Halogen, OH, OR, withdraw electrons inductively

so that they deactivate the ring

Resonance interactions are generally weaker,

affecting orientation

The strongest effects dominate

41
 An Explanation of Substituent Effects
Activating
groups donate
electrons to the
ring, stabilizing
the Wheland
intermediate
(carbocation)

Deactivating
groups withdraw
electrons from
the ring,
destabilizing the
Wheland
intermediate
42
43
 Ortho- and Para-Directing Activators: Alkyl Groups

Alkyl groups activate: direct further

substitution to positions ortho and para to
themselves

Alkyl group is most effective in the ortho

and para positions

44
45
 Ortho- and Para-Directing Activators: OH and NH2

Alkoxyl, and amino groups have a strong,

electron-donating resonance effect

Most pronounced at the ortho and para

positions

46
47
 Ortho- and Para-Directing Deactivators: Halogens

Electron-withdrawing inductive effect

outweighs weaker electron-donating
resonance effect

Resonance effect is only at the ortho and

para positions, stabilizing carbocation
intermediate

48
49
 Meta-Directing Deactivators

Inductive and resonance effects reinforce

each other

Ortho and para intermediates destabilized

by deactivation from carbocation
intermediate

Resonance cannot produce stabilization

50
51
Summary Table: Effect of Substituents in Aromatic Substitution

52
53
 Is it ortho/para or meta directing?????

All ortho- and para- directors have a lone

pair of electrons on the atom directly
attached to the ring (with the exception of
alkyl, aryl, and CH=CHR groups).

All meta- directors have a positive charge

or a partial positive charge on the atom
attached to the ring.

54
 In Summary:

All activating substituents are ortho/para

directors

The weakly deactivating halogens are

ortho/para directors

All other deactivating substituents are

meta directors

55
 CH3 Example 4:

+ Br2 FeCl3 NO2

Cl2

toluene FeCl3

nitrobenzene

Br

+ Cl2 FeCl3
O
C CH3

bromobenzene HNO3

H2SO4

benzaldehyde 56
 Example 5:

What product(s) would result from the nitration of

each of the following compounds?

propylbenzene
benzenesulfonic acid
iodobenzene
benzaldehyde
cyclohexylbenzene
benzonitrile

57
 Trisubstituted Benzenes: Additivity of Effects

If the directing effects of the two groups are the

same, the result is additive

58
 Substituents with Opposite Effects

If the directing effects of two groups oppose

each other, the more powerful activating group
decides the principal outcome
Usually gives mixtures of products

59
 Meta-Disubstituted Compounds Are Unreactive

The reaction site is too hindered

To make aromatic rings with three

adjacent substituents, it is best to start
with an ortho-disubstituted compound

60
61
 Example 6:
OCH3
Br2
FeBr3
Br

NH2
Br Br2
FeBr3

NO2
Cl Br2
FeBr3

62
 Nucleophilic Aromatic Substitution

Aryl halides with electron-withdrawing substituents ortho

and para react with nucleophiles
Form addition intermediate (Meisenheimer complex) that
is stabilized by electron-withdrawal
Halide ion is lost

Cl OH
O2N NO2 - O2N NO2
1. OH
2. H3O+

NO2 NO2
2,4,6-trinitrochlorobenzene 2,4,6-trinitrophenol

63
 Mechanism 7: Nucleophilic Aromatic Substitution

Cl 130 C OH
+ -
OH + Cl
NO2 NO2

Cl
Cl
- OH
+ OH
NO2 ..
C
NO2

OH
+ Cl
NO2

64
 Cl 130 C OH
+ -OH + Cl
NO2 NO2

o-chloronitrobenzene

Cl HO
130 C
+ Cl
+ -OH

NO2 NO2

p-chloronitrobenzene

Cl

130 C
+ -
OH NR
NO2

m-chloronitrobenzene

65
 Nucleophilic Aromatic Substitution

Br Na+ -NH2 NH2

+ NaBr
NH 3

No Mechanism

66
 Electrophilic and Nucleophilic Substitution

Electrophilic Sub
Favored by electron donating substituents
Stabilize carbocation intermediate

Nucleophilic Sub
Favored by electron withdrawing substituents
Stabilize carbanion intermediate

67
 Bromination of Alkylbenzene Side Chains

Reaction of an alkylbenzene with N-bromo-

succinimide (NBS) and benzoyl peroxide (radical
initiator) introduces Br into the side chain

68
 Bromination of Alkylbenzene Side Chains

Abstraction of a benzylic hydrogen atom

generates an intermediate benzylic radical
Reacts with Br2 to yield product
Br radical cycles back into reaction to carry
chain

No
Mechanism

69
 Oxidation of Aromatic Compounds

Alkyl side chains can be oxidized to CO2H by

strong reagents such as KMnO4 and Na2Cr2O7 if
they have a C-H next to the ring

Converts an alkylbenzene into a benzoic acid,

ArR ArCO2H

70
 Example 7:

KMnO4
H2O

KMnO4
O2 N H2O

KMnO4
H2O

71
 Reduction of Aromatic Compounds

Aromatic rings are inert to catalytic hydrogenation under

conditions that reduce alkene double bonds

Can selectively reduce an alkene double bond in the

presence of an aromatic ring

Reduction of an aromatic ring requires more powerful

reducing conditions (high pressure or rhodium catalysts)

72
 Reduction of Aryl Alkyl Ketones

Aromatic ring activates neighboring carbonyl group

toward reduction

Ketone is converted into an alkylbenzene by catalytic

hydrogenation over Pd catalyst

73
 Reduction of Aryl Nitro Compounds

NO2 NH2
Fe, H3O+
-
OH

NO2 NH2
SnCl2, H3O+

-
OH

NO2
H2, Pd/C NH2

EtOH

74
 Reduction of Aromatic Ring

H2/Pt in ethanol

2000 psi, 25oC

or
H2/(Rh/C) in ethanol

1 atm, 25oC

75
 Synthesis Strategies

These syntheses require planning and

consideration of alternative routes

Its important to pay attention to the order in

which substituents are placed on the ring
meta or or ortho/para directing

When should an added substituent be

modified?

76
 Example 8: Synthesize the following

1. m-bromobenzenesulfonic acid from benzene

2. p-bromobenzenesulfonic acid from benzene

3. p-propylbenzenesulfonic acid from benzene

4. 2-bromo-4-ethylphenol from benzene

77