ORGANIC CHEMISTRY On-Line

Electrophilic Aromatic Substitution

Characteristic reaction of benzene (& other aromatics) — a hydrogen

atom is replaced by an electrophile

Benzene has 6 p electrons delocalized in 6 p-orbitals overlapping

above and below the plane of the ring
The loosely-held p electrons make the benzene ring electron rich
The 6 p electrons satisfy Hückel's rule, making benzene very stable

Electrophilic aromatic
substitution
 ORGANIC CHEMISTRY On-Line

Electrophilic Aromatic Substitution

Benzene does not undergo addition reactions like other unsaturated
hydrocarbons, because addition would yield a product that is not
aromatic
Substitution of a hydrogen keeps the aromatic ring intact
 ORGANIC CHEMISTRY On-Line

Electrophilic Aromatic Substitution

Five main examples of electrophilic aromatic substitution
 ORGANIC CHEMISTRY On-Line

EAS: General Mechanism

Regardless of the electrophile used, all EAS reactions occur by the
same two-step mechanism — addition of the electrophile (E+) to
form a resonance-stabilized carbocation, followed by deprotonation
with base
 ORGANIC CHEMISTRY On-Line

EAS: General Mechanism

The first step in electrophilic aromatic substitution forms a
carbocation, for which three resonance structures can be drawn
 ORGANIC CHEMISTRY On-Line

EAS: General Mechanism

Energy changes in EAS:
 ORGANIC CHEMISTRY On-Line

EAS: Halogenation
In halogenation, benzene reacts with Cl2 or Br2 in the presence of a
Lewis acid catalyst, such as FeCl3 or FeBr3, to give the aryl halides
chlorobenzene or bromobenzene respectively
Analogous reactions with I2 and F2 are not synthetically useful
because I2 is too unreactive and F2 reacts too violently
 ORGANIC CHEMISTRY On-Line

EAS: Halogenation Mechanism

 ORGANIC CHEMISTRY On-Line

EAS: Nitration
Nitration introduce the nitro group onto the aromatic ring

A mixture of conc. nitric and sulphuric acids forms the electrophile

nitronium ion (NO2+)

It is generated from nitric acid by protonation and loss of water

 ORGANIC CHEMISTRY On-Line

EAS: Nitration
The nitronium ion reacts with benzene to yield a carbocation intermediate

Loss of a proton from this intermediate yields the neutral substitution

product

Nitration is especially useful because the nitro group can be reduced

to the NH2 group
 ORGANIC CHEMISTRY On-Line

EAS: Sulphonation
Sulphonation introduce the sulphonic group onto the aromatic ring
Reaction occurs with sulphuric acid and sulphur trioxide ("fuming
sulphuric acid"), with the product being benzene sulphonic acid
The reactive electrophile is either SO3H+ or neutral SO3
 ORGANIC CHEMISTRY On-Line

EAS: Sulphonation
The reaction is reversible, depending on the reaction conditions
Sulphonation is favoured in strong acid, whereas de-sulphonation
is favoured in hot, dilute aqueous acid
 ORGANIC CHEMISTRY On-Line

EAS: Friedel-Crafts Alkylation

In Friedel-Crafts alkylation, treatment of benzene with an alkyl

halide and a Lewis acid (AlCl3) forms an alkyl benzene
 ORGANIC CHEMISTRY On-Line

EAS: Friedel-Crafts Alkylation Mechanism

 ORGANIC CHEMISTRY On-Line

EAS: Friedel-Crafts Alkylation Mechanism

 ORGANIC CHEMISTRY On-Line

EAS: Friedel-Crafts Alkylation

Limitations: Alkyl halide

Three additional facts about the Friedel-Crafts alkylation should

be kept in mind:
[1] Vinyl halides and aryl halides do not react in Friedel-Crafts
alkylation
 ORGANIC CHEMISTRY On-Line

EAS: Friedel-Crafts Alkylation

Limitations: Carbocation Rearrangements

[2] Rearrangements can occur

These results can be explained by carbocation rearrangements

 ORGANIC CHEMISTRY On-Line

EAS: Friedel-Crafts Alkylation

Limitations: Carbocation Rearrangements
 ORGANIC CHEMISTRY On-Line

EAS: Friedel-Crafts Alkylation

Limitations: Carbocation Rearrangements
Rearrangements can occur even when no free carbocation is
formed initially
 ORGANIC CHEMISTRY On-Line

EAS: Friedel-Crafts Alkylation

Limitations: Functional groups
[3] Other functional groups that form carbocations can also be
used as starting materials
 ORGANIC CHEMISTRY On-Line

EAS: Friedel-Crafts Alkylation

Limitations: Functional groups
Each carbocation can then go on to react with benzene to form a
product of electrophilic aromatic substitution
 ORGANIC CHEMISTRY On-Line

EAS: Friedel-Crafts Alkylation

Limitations: Functional groups
Starting materials that contain both a benzene ring and an
electrophile are capable of intramolecular Friedel-Crafts reactions
 ORGANIC CHEMISTRY On-Line

Limitations
1. Aromatic halides and vinylic
halides do not react.
2. Rings containing EWG and basic
amino groups do not undergo
alkylation.
3. Polyalkylation occurs.
4. Rearrangement of the alkyl
carbocations.
 ORGANIC CHEMISTRY On-Line

EAS: Friedel-Crafts Acylation

In Friedel-Crafts acylation, a benzene ring is treated with an acid
chloride (RCOCl) and AlCl3 to form a ketone
 ORGANIC CHEMISTRY On-Line

EAS: Friedel-Crafts Acylation Mechanism

The Lewis acid AlCl3 ionizes the carbon-halogen bond of the acid
chloride, thus forming a positively-charged carbon electrophile called
an acylium ion, which is resonance-stabilized
The positively-charged carbon atom of the acylium ion then goes on
to react with benzene in the two step mechanism
 ORGANIC CHEMISTRY On-Line

Limitation
1. Rings containing EWG and basic
amino groups do not undergo
acylation.
 ORGANIC CHEMISTRY On-Line

Oxidation and Reduction of Substituted Benzenes

Arenes containing at least one benzylic C—H bond are oxidized with
KMnO4 to benzoic acid

Substrates with more than one alkyl group are oxidized to dicarboxylic
acids; compounds without a benzylic hydrogen are inert to oxidation
 ORGANIC CHEMISTRY On-Line

Oxidation and Reduction of Substituted Benzenes

Ketones formed as products of Friedel-Crafts acylation can be reduced
to alkyl benzenes by two different methods:
1. The Clemmensen reduction—uses zinc and mercury in the
presence of strong acid
2. The Wolff-Kishner reduction—uses hydrazine (NH2NH2) and
strong base (KOH)
 ORGANIC CHEMISTRY On-Line

Oxidation and Reduction of Substituted Benzenes

There are two different ways to introduce an alkyl group on a
benzene ring:
1. A one-step method using Friedel-Crafts alkylation
2. A two-step method using Friedel-Crafts acylation to form a
ketone, followed by reduction
 ORGANIC CHEMISTRY On-Line

Oxidation and Reduction of Substituted Benzenes

Although the two-step method seems more roundabout, it must be
used to synthesize certain alkyl benzenes that cannot be prepared by
the one-step Friedel-Crafts alkylation because of rearrangements
 ORGANIC CHEMISTRY On-Line

Oxidation and Reduction of Substituted Benzenes

A nitro group that has been introduced on a benzene ring by

nitration can readily be reduced to an amino group under a variety
of conditions
 ORGANIC CHEMISTRY On-Line

EAS: Substituted Benzenes

Many substituted benzene rings undergo EAS

Each substituent either increases or decreases the electron density in
the benzene ring, and this affects the course of EAS
Donation of electron density makes benzene more electron rich
Withdrawal of electron density makes benzene less electron rich
Atoms more electron-rich than carbon (N, O & X) pull electron
density away from carbon (electron-withdrawing inductive effect)
Polarizable alkyl groups donate electron density (exhibit an electron-
donating inductive effect)
 ORGANIC CHEMISTRY On-Line

EAS: Substituted Benzenes

EAS is a general reaction of all aromatic compounds, including

polycyclic aromatic hydrocarbons, heterocycles, and substituted
benzene derivatives
A substituent affects two aspects of the EAS reaction:
The rate of the reaction — substituted benzene reacts faster or
slower than benzene itself
The orientation of substitution — the new group is located
either ortho, meta, or para to the existing substituent; the first
substituent determines the position of the second incoming
substituent
 ORGANIC CHEMISTRY On-Line

EAS: Substituted Benzenes

All substituents can be divided into three general types:
 ORGANIC CHEMISTRY On-Line

EAS: Substituted Benzenes

 ORGANIC CHEMISTRY On-Line

EAS: Substituted Benzenes

 ORGANIC CHEMISTRY On-Line

EAS: Substituted Benzenes

The reactivity and directing

effects of common substituted
benzenes
 ORGANIC CHEMISTRY On-Line

EAS: Substituted Benzenes

Considering inductive effects only, the NH2 group withdraws electron

density and CH3 donates electron density
 ORGANIC CHEMISTRY On-Line

EAS: Substituted Benzenes

Resonance effects are only observed with substituents containing
lone pairs or p bonds

An electron-donating resonance effect is observed whenever an

atom/group having lone pairs is directly bonded to a benzene ring
 ORGANIC CHEMISTRY On-Line

EAS: Substituted Benzenes

An electron-withdrawing resonance effect is observed in substituted
benzenes having the general structure:
C6H5-Y=Z, where Z is more electronegative than Y
Seven resonance structures can be drawn for benzaldehyde
(C6H5CHO)
Three of them place a positive charge on a carbon atom of the
benzene ring, the CHO group withdraws electrons from the
benzene ring by a resonance effect
 ORGANIC CHEMISTRY On-Line

EAS: Substituted Benzenes

To predict whether a substituted benzene is more or less electron

rich than benzene itself, consider the net balance of both the
inductive- and resonance effects
Alkyl groups donate electrons by an inductive effect, but they have
no resonance effect (no non-bonded electron pairs or p bonds)
Any alkyl-substituted benzene is more electron rich than benzene
itself
 ORGANIC CHEMISTRY On-Line

EAS: Substituted Benzenes

The inductive- and resonance effects in compounds having the general

structure C6H5-Y=Z (Z more electronegative than Y) are both electron-
withdrawing
 ORGANIC CHEMISTRY On-Line

EAS: Substituted Benzenes

These compounds represent examples of the general structural
features in electron-donating and electron-withdrawing substituents
 ORGANIC CHEMISTRY On-Line

EAS: Substituted Benzenes

Toluene
Toluene reacts faster than benzene in all substitution reactions
The electron-donating CH3 group activates the benzene ring to
electrophilic attack
Ortho and para products predominate
The CH3 group is called an ortho, para director
 ORGANIC CHEMISTRY On-Line

EAS: Substituted Benzenes

Nitrobenzene
It reacts slower than benzene in all substitution reactions
The electron-withdrawing NO2 group deactivates the benzene ring to
electrophilic attack
The meta product predominates
The NO2 group is called a meta director
 ORGANIC CHEMISTRY On-Line

EAS: Substituted Benzenes

Halogens
Halogens are in a class by themselves
 ORGANIC CHEMISTRY On-Line

EAS: Substituted Benzenes

To evaluate the effects of a given substituent, we can use the

following stepwise procedure:
 ORGANIC CHEMISTRY On-Line

EAS: Substituted Benzenes

A CH3 group directs electrophilic attack ortho and para to itself
because an electron-donating inductive effect stabilizes the carbocation
intermediate
 ORGANIC CHEMISTRY On-Line

EAS: Substituted Benzenes

An NH2 group directs electrophilic attack ortho and para to itself
because the carbocation intermediate has additional resonance
stabilization
 ORGANIC CHEMISTRY On-Line

EAS: Substituted Benzenes

With the NO2 group (and all meta directors) meta attack occurs
because attack at the ortho and para position gives a destabilized
carbocation intermediate
 ORGANIC CHEMISTRY On-Line

QUESTIONS
1. Identify each group as having an electron-donating or electron-
withdrawing inductive effect.
(a). CH3CH2CH2CH2―

(b). Br―

(c). CH3CH2O―
 ORGANIC CHEMISTRY On-Line

QUESTIONS
2. Draw the resonance structures and use them to determine whether there is
an electron-donating or withdrawing resonance effect
OCH3

(a).
OCH3 OCH3 OCH3
OCH3

OCH3
 ORGANIC CHEMISTRY On-Line

QUESTIONS
O O O
O

(b).

O
O O

O
 ORGANIC CHEMISTRY On-Line

QUESTIONS
3. Identify as electron-donating or electron-withdrawing
OCH3

(a).

(b).

C(CH3)3

(c).
 ORGANIC CHEMISTRY On-Line

QUESTIONS
4. Predict the products for the following reactions

OCH3

CH3CH2Cl
(a).
AlCl3

Br
HNO3
(b). H2SO4
 ORGANIC CHEMISTRY On-Line

QUESTIONS

NO2

Cl2
(c).
FeCl3
 ORGANIC CHEMISTRY On-Line

QUESTIONS
5. Label each compound as less or more reactive than benzene
C(CH3)3
OH

(a). (b).

OH

N(CH3)3
OCH2CH3
(c). (d).
 ORGANIC CHEMISTRY On-Line

• Primary arylamines react with nitrous acid

(HNO2) to yield stable arenediazonium salts.
+
N
a
N
O
2H
C
l
/
H
S
O
2
4
H
N
O
2

• Diazotization N
H
2
H
N
O
2
N
N

H
S
O
24

The diazonio group (N2) can be replaced by a Nu- in

a substitution reaction.
N
N -
N
u N
u

+N
2
 ORGANIC CHEMISTRY On-Line

Diazonium salts reactions

Br
CuB r

I
N aI

N2 CN COOH
C uCN H 3O +

OH
H 3O +
(o r C u 2O , C u (N O 3)2, H 2O )

H 3P O 2