General

Organic Chemistry
Two credits
Second Semester 2009

King Saud bin Abdulaziz University for Health Science

Reference Book: Organic Chemistry: A Brief Course,

by Robert C. Atkins and Francis A. Carey
Third Edition

Instructor: Rabih O. Al-Kaysi, PhD.

 Lecture 11

Chapter 6

AROMATIC COMPOUNDS
 Reactions of Arenes:
A Preview

1. Some reactions involve the ring.

2. In other reactions the ring is a substituent.
1. Reactions involving the ring
a) Reduction
Catalytic hydrogenation
Birch reduction
b) Electrophilic aromatic substitution

c) Nucleophilic aromatic substitution

2. The ring as a substituent

 Reduction
Reductionof
ofBenzene
BenzeneRings
Rings

catalytic H Birch reduction

hydrogenation
H H

H H

H H H H H
H H
H H
H H
H H
H H H
H
H H H H
The Birch Reduction
 Birch
BirchReduction
Reductionof
ofBenzene
Benzene

H H H
H H Na, NH3 H H

CH3OH
H H H H

H H H
(80%)
Product is non-conjugated diene.
Reaction stops here. There is no further reduction.
Reaction is not hydrogenation. H2 is not involved in any way.
Oxidation of Alkylbenzenes
Site
Siteof
ofOxidation
OxidationisisBenzylic
BenzylicCarbon
Carbon

CH3

or Na2Cr2O7
O
H2SO4
CH2R COH
H2O
or heat

CHR2
Example
Example
O
CH(CH3)2 COH
Na2Cr2O7
H2SO4
H2O
heat
CH3 COH

O
(45%)
Addition Reactions of
Alkenylbenzenes
•hydrogenation
•halogenation
•addition of hydrogen halides
 Hydrogenation
Hydrogenation
CH3 CH3

C CHCH3 CHCH2CH3
H2

Pt
Br Br
(92%)
 Halogenation
Halogenation

Br2
CH CH2 CH CH2

Br Br

(82%)
Addition
Addition of
of Hydrogen
Hydrogen Halides
Halides
Cl

HCl

(75-84%)
Polymerization of
Styrene
Polymerization
Polymerization of
of Styrene
Styrene

H2C CHC6H5

CH2 CH CH2 CH CH2 CH

C6H5 C6H5 C6H5

polystyrene
 Reactions of Arenes:
Electrophilic Aromatic Substitution

H E
+ –
+E Y +H Y
 H E
+ –
+E Y +H Y

Electrophilic
Electrophilic aromatic
aromatic substitutions
substitutions include:
include:

Nitration
Sulfonation
Halogenation
Friedel-Crafts Alkylation
Friedel-Crafts Acylation
 Nitration
Nitrationof
ofBenzene
Benzene

H H2SO4 NO2
+ HONO2
+ H2O

Nitrobenzene
(95%)
 Sulfonation
Sulfonationof
ofBenzene
Benzene

H heat SO2OH
+ HOSO2OH
+ H2O

Benzenesulfonic acid
(100%)
 Halogenation
Halogenationof
ofBenzene
Benzene

H FeBr3 Br2
+ Br2
+ HBr

Bromobenzene
(65-75%)
Friedel-Crafts
Friedel-CraftsAlkylation
Alkylationof
ofBenzene
Benzene

H AlCl3 C(CH3)3
+ (CH3)3CCl
+ HCl

tert-Butylbenzene
(60%)
Friedel-Crafts
Friedel-CraftsAcylation
Acylationof
ofBenzene
Benzene

O
O
H AlCl3 CCH2CH3
+ CH3CH2CCl
+ HCl

1-Phenyl-1-propanone
(88%)
 Mechanistic Principles
of
Electrophilic Aromatic Substitution
Step
Step1:1: attack
attackof
ofelectrophile
electrophile
on-electron
on -electronsystem
systemofofaromatic
aromaticring
ring

E+
H H H H E
H H H +
H
H H H H

highly endothermic
carbocation is allylic, but not aromatic
Step
Step2:
2: loss
lossof
ofaaproton
protonfrom
fromthe
thecarbocation
carbocation
intermediate
intermediate

H H H H E
H E H +
H
H H H+ H H

highly exothermic
this step restores aromaticity of ring
Nitration of Benzene
Nitration
Nitrationof
ofBenzene
Benzene

H H2SO4 NO2
+ HONO2
+ H2O

+
Electrophile is
•• O
••
N O ••
••
nitronium ion
Step
Step1:1: attack
attackof
ofnitronium
nitroniumcation
cation
on-electron
on -electronsystem
systemof ofaromatic
aromaticring
ring

NO2+
H H H H NO2
H H H +
H
H H H H
Step
Step2:
2: loss
lossof
ofaaproton
protonfrom
fromthe
thecarbocation
carbocation
intermediate
intermediate

H H H H NO2
H NO2 H +
H
H H H+ H H
Halogenation of Benzene
 Halogenation
Halogenationof
ofBenzene
Benzene

H FeBr3 Br2
+ Br2
+ HBr

Electrophile is a Lewis acid-Lewis base

complex between FeBr3 and Br2.
 The
TheBr
Br2-FeBr
-FeBr3 Complex
2 3 Complex

+
•• •• •• •• –
•• Br Br •• + FeBr3 •• Br Br FeBr3
•• •• •• ••

Lewis base Lewis acid Complex

The Br2-FeBr3 complex is more electrophilic

than Br2 alone.
 Step
Step1:1: attack
attackof
ofBr
Br2-FeBr
-FeBr3 complex
2 3 complex

on-electron
on -electronsystem
systemof ofaromatic
aromaticring
ring

+ –
Br Br FeBr3
H H H H Br
H H H +
H
H H H H

+ FeBr4–
Step
Step2:
2: loss
lossof
ofaaproton
protonfrom
fromthe
thecarbocation
carbocation
intermediate
intermediate

H H H H Br
H Br H +
H
H H H+ H H
 Rate and Regioselectivity in
Electrophilic Aromatic Substitution

A substituent already present on the ring

can affect both the rate and regioselectivity
of electrophilic aromatic substitution.
 Effect
Effecton
onRate
Rate

Activating substituents increase the rate

of EAS compared to that of benzene.
Deactivating substituents decrease
the rate of EAS compared to benzene.
 Methyl
MethylGroup
Group

Toluene undergoes nitration

CH3
20-25 times faster than
benzene.
A methyl group is an
activating substituent.
 Trifluoromethyl
TrifluoromethylGroup
Group

(Trifluoromethyl)benzene
CF3
undergoes nitration 40,000
times more slowly than benzene .
A trifluoromethyl group is a
deactivating substituent.
 Effect
Effecton
onRegioselectivity
Regioselectivity

Ortho-para directors direct an incoming

electrophile to positions ortho and/or
para to themselves.
Meta directors direct an incoming
electrophile to positions meta to
themselves.
 Nitration
Nitrationof
ofToluene
Toluene

CH3 CH3 CH3 CH3

NO2
HNO3
+ +
acetic
NO2
anhydride
NO2

63% 3% 34%
o- and p-nitrotoluene together comprise 97%
of the product
a methyl group is an ortho-para director
 Nitration
Nitrationof
of(Trifluoromethyl)benzene
(Trifluoromethyl)benzene

CF3 CF3 CF3 CF3

NO2
HNO3
+ +
H2SO4
NO2
NO2

6% 91% 3%
m-nitro(trifluoromethyl)benzene comprises
91% of the product
a trifluoromethyl group is a meta director
Rate and Regioselectivity
in the
Nitration of Toluene
 Carbocation
CarbocationStability
StabilityControls
ControlsRegioselectivity
Regioselectivity

CH3 CH3 CH3

NO2
H H H H H
H +
+ +
H H H H H H
NO2
H H NO2 H
gives ortho gives para gives meta
 Carbocation
CarbocationStability
StabilityControls
ControlsRegioselectivity
Regioselectivity

CH3 CH3 CH3

NO2
H H H H H
H +
+ +
H H H H H H
NO2
H H NO2 H
gives ortho gives para gives meta

more stable less stable

 ortho
orthoNitration
Nitrationof
ofToluene
Toluene

CH3
NO2
H
H
+
H H

H
 ortho
orthoNitration
Nitrationof
ofToluene
Toluene

CH3 CH3
NO2 NO2
H H
H H
+ +
H H H H

H H
 ortho
orthoNitration
Nitrationof
ofToluene
Toluene

CH3 CH3 CH3

NO2 NO2 NO2
H H H +
H H H
+ +
H H H H H H

H H H
this resonance
form is a
tertiary
carbocation
 ortho
orthoNitration
Nitrationof
ofToluene
Toluene

CH3 CH3 CH3

NO2 NO2 NO2
H H H +
H H H
+ +
H H H H H H

H H H

the rate-determining intermediate in the ortho

nitration of toluene has tertiary carbocation
character
 para
paraNitration
Nitrationof
ofToluene
Toluene

CH3

H H
+
H H
H NO2
 para
paraNitration
Nitrationof
ofToluene
Toluene

CH3 CH3

H H H + H
+
H H H H
H NO2 H NO2
this resonance
form is a tertiary
carbocation
 para
paraNitration
Nitrationof
ofToluene
Toluene

CH3 CH3 CH3

H H H + H H H
+ +
H H H H H H
H NO2 H NO2 H NO2
this resonance
form is a tertiary
carbocation
 para
paraNitration
Nitrationof
ofToluene
Toluene

CH3 CH3 CH3

H H H + H H H
+ +
H H H H H H
H NO2 H NO2 H NO2

the rate-determining intermediate in the para

nitration of toluene has tertiary carbocation
character
 meta
metaNitration
Nitrationof
ofToluene
Toluene

CH3

H H
+

H H
NO2
H
 meta
metaNitration
Nitrationof
ofToluene
Toluene

CH3 CH3

H H H H
+ +

H H H H
NO2 NO2
H H
 meta
metaNitration
Nitrationof
ofToluene
Toluene

CH3 CH3 CH3

H H H H H H
+ +

H H H H H + H
NO2 NO2 NO2
H H H
all the resonance forms of the rate-
determining intermediate in the meta nitration
of toluene have their positive charge on a
secondary carbon
 Nitration
Nitrationof
ofToluene:
Toluene: Interpretation
Interpretation

• The rate-determining intermediates for ortho and

para nitration each have a resonance form that is
a tertiary carbocation. All of the resonance forms
for the rate-determining intermediate in meta
nitration are secondary carbocations.
• Tertiary carbocations, being more stable, are
formed faster than secondary ones. Therefore,
the intermediates for attack at the ortho and para
positions are formed faster than the intermediate
for attack at the meta position. This explains why
the major products are o- and p-nitrotoluene.
 Nitration
Nitrationof
ofToluene:
Toluene: Partial
PartialRate
RateFactors
Factors

• The experimentally determined reaction rate can

be combined with the ortho/meta/para distribution
to give partial rate factors for substitution at the
various ring positions.
• Expressed as a numerical value, a partial rate
factor tells you by how much the rate of
substitution at a particular position is faster (or
slower) than at a single position of benzene.
 Rate and Regioselectivity
in the
Nitration of (Trifluoromethyl)benzene
 AAKey
KeyPoint
Point

H3C C+ F3C C+

A methyl group is electron-donating and

stabilizes a carbocation.
Because F is so electronegative, a CF3 group
destabilizes a carbocation.
 Carbocation
CarbocationStability
StabilityControls
ControlsRegioselectivity
Regioselectivity

CF3 CF3 CF3

NO2
H H H H H
H +
+ +
H H H H H H
NO2
H H NO2 H
gives ortho gives para gives meta
 Carbocation
CarbocationStability
StabilityControls
ControlsRegioselectivity
Regioselectivity

CF3 CF3 CF3

NO2
H H H H H
H +
+ +
H H H H H H
NO2
H H NO2 H
gives ortho gives para gives meta

less stable more stable

Substituent Effects in Electrophilic
Aromatic Substitution:
Activating Substituents
 Table
Table12.2
12.2

Classification of Substituents in Electrophilic

Aromatic Substitution Reactions

Very strongly activating

Strongly activating
Activating
Standard of comparison is H
Deactivating
Strongly deactivating
Very strongly deactivating
 Generalizations
Generalizations

1. All activating substituents are

ortho-para directors.
2. Halogen substituents are slightly
deactivating but ortho-para directing.

3. Strongly deactivating substituents are

meta directors.
 Electron-Releasing
Electron-ReleasingGroups
Groups(ERGs)
(ERGs)

are ortho-para directing and activating

ERG

ERGs include —R, —Ar, and —C=C

 Electron-Releasing
Electron-ReleasingGroups
Groups(ERGs)
(ERGs)

are ortho-para directing and strongly activating

ERG

ERGs such as —OH, and —OR are

strongly activating
 Nitration
Nitrationof
ofPhenol
Phenol

occurs about 1000 times faster than nitration

of benzene
OH OH OH
NO2
HNO3
+

NO2

44% 56%
 Bromination
Brominationof
ofAnisole
Anisole

FeBr3 catalyst not necessary

OCH3 OCH3

Br2

acetic
acid
Br
90%
 Electron-Releasing
Electron-ReleasingGroups
Groups(ERGs)
(ERGs)

•• ERG

ERGs with a lone pair on the atom directly

attached to the ring are ortho-para directing
and strongly activating
 Examples
Examples
O
••
•• OH •• ••
•• ERG = •• OR •• OCR

O
•• NH2 •• NHR •• NR2 •• NHCR

All of these are ortho-para directing

and strongly to very strongly activating