Benzene and its Derivatives

Mrs. Sahaya M Nadar

Department of Pharmaceutical Chemistry

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Substituents on Benzene

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 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.

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 Substituted Benzenes

Considering inductive effects only, the NH2 group withdraws electron

density and CH3 donates electron density.

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 Substituted Benzenes

Resonance effects are only observed with substituents containing lone

pairs or  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.

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 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.

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 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  bonds.

• Thus, any alkyl-substituted benzene is more electron rich than benzene itself.

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 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.

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 Substituted Benzenes

• These compounds represent examples of the general structural features

in electron-donating and electron withdrawing substituents.

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 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:
• The rate of the reaction—A substituted benzene reacts faster or slower
than benzene itself.
• 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.

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 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.

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 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.

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 Electrophilic Aromatic Substitution
and Substituted Benzenes.

All substituents can be divided into three general types:

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Electrophilic Aromatic Substitution and Substituted Benzenes.

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 Electrophilic Aromatic Substitution and Substituted Benzenes.

• Keep in mind that halogens are in a class by themselves.

• Also note that:

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 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.

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 Electrophilic Aromatic Substitution and Substituted Benzenes.

• The principles of inductive effects and resonance effects can now be used to
predict carbocation stability.

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 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 non-bonded 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.

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 Orientation Effects in Substituted Benzenes

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

stepwise procedure:

Most Stable Carbocation 20

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

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

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

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The reactivity and directing effects of common substituted benzenes

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The reactivity and directing effects of common substituted benzenes

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 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.

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 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.

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 Limitations in Electrophilic Aromatic Substitutions

• Treatment of benzene with an alkyl halide and AlCl3 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.

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Disubstituted Benzenes

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 Disubstituted Benzenes

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

substituent is located on the position directed by both groups.

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 Disubstituted Benzenes

2. If the directing effects of two groups oppose each other, the more
powerful activator “wins out.”

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 Disubstituted Benzenes

3. No substitution occurs between two meta substituents because of

crowding.

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 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.

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Pathway I, in which bromination precedes nitration, yields the desired
product. Pathway II yields the undesired meta isomer.

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 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.

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 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.

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Formations:

i) Nitration: m-Dintrobenzene

ii) Halogenation: p-Bromoacetanilide

iii) 2,4,6-Tribromoaniline

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