Chapter 18

Electrophilic Aromatic Substitution

Organic Chemistry, Second Edition

Janice Gorzynski Smith
University of Hawai’i

Prepared by Rabi Ann Musah

State University of New York at Albany

Copyright © The McGraw-Hill Companies, Inc.

Permission required for reproduction or display.
1
 Background

• The characteristic reaction of benzene is electrophilic aromatic

substitution—a hydrogen atom is replaced by an electrophile.

2
 Background

• 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.
• There are five main examples of electrophilic aromatic
substitution.

3
Figure 18.1
Five examples of
electrophilic
aromatic substitution

4
 Background
• Regardless of the electrophile used, all electrophilic aromatic
substitution reactions occur by the same two-step
mechanism—addition of the electrophile E+ to form a
resonance-stabilized carbocation, followed by deprotonation
with base, as shown below:

5
 Background
• The first step in electrophilic aromatic substitution forms a
carbocation, for which three resonance structures can be
drawn. To help keep track of the location of the positive
charge:

6
 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.

7
 Halogenation

• Chlorination proceeds by a similar mechanism.

8
 Figure 18.3
Halogenation Examples of
biologically active
aryl chlorides

9
 Nitration and Sulfonation

• Nitration and sulfonation introduce two different functional

groups into the aromatic ring.
• Nitration is especially useful because the nitro group can be
reduced to an NH2 group.

10
 Nitration and Sulfonation

• Generation of the electrophile in nitration requires

strong acid.

11
 Nitration and Sulfonation

• Generation of the electrophile in sulfonation requires

strong acid.

12
Friedel-Crafts Alkylation and Friedel-Crafts Acylation

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

alkyl halide and a Lewis acid (AlCl3) forms an alkyl
benzene.

13
Friedel-Crafts Alkylation and Friedel-Crafts Acylation

• In Friedel-Crafts acylation, a benzene ring is treated with

an acid chloride (RCOCl) and AlCl3 to form a ketone.
• Because the new group bonded to the benzene ring is
called an acyl group, the transfer of an acyl group from
one atom to another is an acylation.

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15
Friedel-Crafts Alkylation and Friedel-Crafts Acylation

16
Friedel-Crafts Alkylation and Friedel-Crafts Acylation

• In Friedel-Crafts acylation, 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 of
electrophilic aromatic substitution.

17
Friedel-Crafts Alkylation and Friedel-Crafts Acylation

Three additional facts about Friedel-Crafts alkylation

should be kept in mind.

[1] Vinyl halides and aryl halides do not react in Friedel-

Crafts alkylation.

18
Friedel-Crafts Alkylation and Friedel-Crafts Acylation

[2] Rearrangements can occur.

These results can be explained by carbocation

rearrangements.
19
Friedel-Crafts Alkylation and Friedel-Crafts Acylation

20
Friedel-Crafts Alkylation and Friedel-Crafts Acylation

Rearrangements can occur even when no free carbocation

is formed initially.

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Friedel-Crafts Alkylation and Friedel-Crafts Acylation

[3] Other functional groups that form carbocations can

also be used as starting materials.

22
Friedel-Crafts Alkylation and Friedel-Crafts Acylation

Each carbocation can then go on to react with benzene to

form a product of electrophilic aromatic substitution. For
example:

23
Friedel-Crafts Alkylation and Friedel-Crafts Acylation

Starting materials that contain both a benzene ring and an

electrophile are capable of intramolecular Friedel-Crafts
reactions.

24
 Friedel-Crafts Alkylation and Friedel-Crafts Acylation

Figure 18.4 Intramolecular Friedel-Crafts acylation in the synthesis of LSD

25
 Substituted Benzenes

Many substituted benzene rings undergo electrophilic

aromatic substitution.
Each substituent either increases or decreases the
electron density in the benzene ring, and this affects the
course of electrophilic aromatic substitution.

26
 Substituted Benzenes

Considering inductive effects only, the NH2 group

withdraws electron density and CH3 donates electron
density.

27
 Substituted Benzenes

Resonance effects are only observed with substituents

containing lone pairs or π bonds.

An electron-donating resonance effect is observed

whenever an atom Z having a lone pair of electrons is
directly bonded to a benzene ring.

28
 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). Because 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.

29
 Substituted Benzenes

• To predict whether a substituted benzene is more or less

electron rich than benzene itself, we must consider the
net balance of both the inductive and resonance effects.
• For example, alkyl groups donate electrons by an
inductive effect, but they have no resonance effect
because they lack nonbonded electron pairs or π bonds.
• Thus, any alkyl-substituted benzene is more electron
rich than benzene itself.

30
 Substituted Benzenes

• The inductive and resonance effects in compounds having the

general structure C6H5-Y=Z (with Z more electronegative than Y)
are both electron withdrawing.

31
 Substituted Benzenes

• These compounds represent examples of the general

structural features in electron-donating and electron
withdrawing substituents.

32
 Electrophilic Aromatic Substitution
and Substituted Benzenes.

• Electrophilic aromatic substitution is a general reaction

of all aromatic compounds, including polycyclic
aromatic hydrocarbons, heterocycles, and substituted
benzene derivatives.
• A substituent affects two aspects of the electrophilic
aromatic substitution reaction:
1. The rate of the reaction—A substituted benzene
reacts faster or slower than benzene itself.
2. The orientation—The new group is located either
ortho, meta, or para to the existing substituent.
The identity of the first substituent determines the
position of the second incoming substituent.
33
 Electrophilic Aromatic Substitution
and Substituted Benzenes.

• Consider 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.

34
 Electrophilic Aromatic Substitution
and Substituted Benzenes.
• Consider nitrobenzene—It reacts more slowly 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.

35
 Electrophilic Aromatic Substitution
and Substituted Benzenes.

All substituents can be divided into three general types:

36
Electrophilic Aromatic Substitution and Substituted Benzenes.

37
Electrophilic Aromatic Substitution and Substituted Benzenes.

• Keep in mind that halogens are in a class by

themselves.
• Also note that:

38
Electrophilic Aromatic Substitution and Substituted Benzenes.

• To understand how substituents activate or deactivate the ring,

we must consider the first step in electrophilic aromatic
substitution.
• The first step involves addition of the electrophile (E+) to form a
resonance stabilized carbocation.
• The Hammond postulate makes it possible to predict the relative
rate of the reaction by looking at the stability of the carbocation
intermediate.

39
Electrophilic Aromatic Substitution and Substituted Benzenes.

• The principles of inductive effects and resonance effects can

now be used to predict carbocation stability.

40
41
 Orientation Effects in Substituted Benzenes
• There are two general types of ortho, para directors and
one general type of meta director.
• All ortho, para directors are R groups or have a
nonbonded electron pair on the atom bonded to the
benzene ring.
• All meta directors have a full or partial positive charge
on the atom bonded to the benzene ring.

42
 Orientation Effects in Substituted Benzenes

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

the following stepwise procedure:

43
• A CH3 group directs electrophilic attack ortho and para to itself
because an electron-donating inductive effect stabilizes the
carbocation intermediate.

44
• An NH2 group directs electrophilic attack ortho and para to itself
because the carbocation intermediate has additional resonance
stabilization.

45
• With the NO2 group (and all meta directors) meta attack occurs
because attack at the ortho and para position gives a destabilized
carbocation intermediate.

46
Figure 18.7 The reactivity and directing effects of common substituted benzenes

47
Figure 18.7 The reactivity and directing effects
of common substituted benzenes

48
 Limitations in Electrophilic Aromatic Substitutions

• Benzene rings activated by strong electron-donating

groups—OH, NH2, and their derivatives (OR, NHR, and
NR2)—undergo polyhalogenation when treated with X2 and FeX3.

49
 Limitations in Electrophilic Aromatic Substitutions

• A benzene ring deactivated by strong electron-withdrawing

groups (i.e., any of the meta directors) is not electron rich
enough to undergo Friedel-Crafts reactions.

• Friedel-Crafts reactions also do not occur with NH2 groups

because the complex that forms between the NH2 group and the
AlCl3 catalyst deactivates the ring towards Friedel-Crafts
reactions.

50
 Limitations in Electrophilic Aromatic Substitutions

• Treatment of benzene with an alkyl halide and AlCl 3 places an

electron-donor R group on the ring. Since R groups activate the
ring, the alkylated product (C6H5R) is now more reactive than
benzene itself towards further substitution, and it reacts again
with RCl to give products of polyalkylation.

• Polysubstitution does not occur with Friedel-Crafts acylation.

51
 Disubstituted Benzenes

1. When the directing effects of two groups reinforce, the

new substituent is located on the position directed by
both groups.

52
 Disubstituted Benzenes

2. If the directing effects of two groups oppose each

other, the more powerful activator “wins out.”

53
 Disubstituted Benzenes

3. No substitution occurs between two meta substituents

because of crowding.

54
 Synthesis of Benzene Derivatives

In a disubstituted benzene, the directing effects indicate

which substituent must be added to the ring first.

Let us consider the consequences of bromination first

followed by nitration, and nitration first, followed by
bromination.
55
Pathway I, in which bromination precedes nitration, yields the
desired product. Pathway II yields the undesired meta isomer.

56
 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.

57
 Oxidation and Reduction of Substituted Benzenes

A nitro group (NO2) that has been introduced on a benzene

ring by nitration with strong acid can readily be reduced to
an amino group (NH2) under a variety of conditions.

58