Chapter 19

Reactions of
Benzene and
Substituted
Benzenes

Paula Yurkanis Bruice

University of California,
Santa Barbara

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 Benzene is an Aromatic Compound

Benzene is cyclic, planar, and has an interrupted cloud of π electrons.

Benzene is an unusually stable compound.

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 The Nomenclature of
Substituted Benzenes

some monosubstituted benzenes are named

just by adding the name of the substituent to “benzene”

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 The Nomenclature of
Substituted Benzenes

some monosubstituted benzenes have names

that incorporate the substituent

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 Phenyl and Benzyl Substituents

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 Aryl Means Benzene
or Substituted Benzene

Each of the structures above could be abbreviated as ArOH.

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 How Benzene Reacts

Aromatic compounds such as benzene undergo

electrophilic aromatic substitution reactions.

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 Benzene Reacts with Electrophiles

The  electrons above and below the ring make benzene a nucleophile.

Benzene attacking an electrophile is like an

alkene attacking an electrophile.
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 Benzene Undergoes Substitution,
Not Addition

Aromaticity is restored in the product from electrophilic substitution.

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 An Electrophilic Aromatic Substitution
Reaction

An electrophile (Y+) substitutes for H+.

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 The Mechanism for
Electrophilic Aromatic Substitution

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 Halogenation of Benzene

Bromination or chlorination of benzene requires a Lewis acid catalyst

because benzene’s aromaticity causes it to be less reactive than an
alkene.
Ferric bromide (FeBr3) or ferric chloride (FeCl3) is usually used.

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Generating the Electrophile for Halogenation

Donating a lone pair to a Lewis acid weakens the Br—Br or Cl—Cl bond.

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 The Mechanism for Halogenation

• The electrophile adds to the benzene ring.

• A base in the reaction mixture removes the proton from the carbon that
attacked the electrophile.
• The catalyst is regenerated.

Chlorination occurs by an analogous mechanism.

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 Iodination of Benzene

The electrophile is generated differently.

Hydrogen peroxide is commonly used as the oxidizing agent.

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 The Mechanism for Iodination

• The electrophile adds to the benzene ring.

• A base in the reaction mixture removes the proton from
the carbon that formed the bond with the electrophile.

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 Nitration of Benzene

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 Generating the Electrophile for Nitration

• Sulfuric acid protonates nitric acid.

• Protonated nitric acid loses water

to form the electrophile (the nitronium ion).

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 The Mechanism for Nitration

• The electrophile adds to the benzene ring.

• A base in the reaction mixture removes the proton from
the carbon that formed the bond with the electrophile.

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 Sulfonation of Benzene

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 Generating the Electrophile for Sulfonation

• Sulfuric acid protonates sulfuric acid.

• Protonated sulfuric acid loses water to form the electrophile
(the sulfonium ion).

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 The Mechanism for Sulfonation

• The electrophile adds to the benzene ring.

• A base in the reaction mixture removes the proton from the carbon
that formed the bond with the electrophile.

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 Sulfonation of Benzene is Reversible

If benzenesulfonic acid is heated in dilute acid,

an H+ adds to the ring and the sulfonic acid group comes off the ring.

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 The Mechanism for Desulfonation

• The electrophile adds to the benzene ring.

• A base in the reaction mixture removes the proton from
the carbon that formed the bond with the electrophile.

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 Friedel–Crafts Substitutions

Two electrophilic substitutions are named for the chemists

Charles Friedel and James Crafts.

• Friedel–Crafts acylation places an acyl group on a benzene ring.

• Friedel–Crafts alkylation places an alkyl group on a benzene ring.

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 Friedel–Crafts Acylation

An acyl chloride or an acid anhydride is the source of the acyl group.

A Lewis acid (AlCl3) is required.

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 The Mechanism for
Friedel–Crafts Acylation

• The electrophile adds to the benzene ring.

• A base in the reaction mixture removes the proton from
the carbon that formed the bond with the electrophile.

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 Generating the Electrophile for
Friedel–Crafts Acylation

The acylium ion is the electrophile.

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 AlCl3 Reacts with the Product of
Friedel–Crafts Acylation

More than one equivalent of AlCl3 must be used in a Friedel–Crafts acylation.

AlCl3 forms a complex with the carbonyl group in the product.

Water is added to the reaction mixture to release the product from the complex.

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 The Gatterman–Koch Reaction

Benzaldehyde cannot be made by a Friedel–Crafts acylation

because the needed acyl chloride (formyl chloride) is unstable.

Formyl chloride is generated in the reaction mixture.

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 Friedel–Crafts Alkylation

An alky halide is the source of the alkyl group.

A Lewis acid (AlCl3) is required.

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 Generation of the Electrophile for
Friedel–Crafts Alkylation

A carbocation is the electrophile.

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 The Mechanism for
Friedel–Crafts Alkylation

• The electrophile adds to the benzene ring.

• A base in the reaction mixture removes the proton from the
carbon that formed the bond with the electrophile.

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 There are Limits to Friedel–Crafts Alkylation

The alkylated benzene product is more reactive than benzene.

Therefore, a large excess of benzene is needed to avoid multiple

alkylations of the ring.

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 Carbocation Rearrangement Leads to
an Undesired Product

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 Carbocation Rearrangement Leads to
an Undesired Product

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 Should We Draw Primary Carbocations?

Friedel–Crafts alkylation mechanisms are written as if a primary carbocation

is formed, although we know that primary carbocations are too unstable to
be formed.

A true primary carbocation is never formed.

Instead, an incipient carbocation is formed.

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 Putting a Straight Chain Alkyl Group
on a Ring

• Add the correct number of carbons with a Friedel–Crafts acylation

reaction.
• Reduce the carbonyl group to a methylene group.

(Catalytic hydrogenation reduces only a carbonyl group adjacent to a benzene ring.)

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 Other Ways to Convert a Carbonyl Group
to a Methylene Group

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 The Mechanism for the
Wolff–Kishner Reduction

• The ketone forms a hydrazone following the mechanism for imine formation.

• A hydroxide ion removes a proton from the weakly acidic NH2 group.

• Reprotonation occurs at carbon.

• Another deprotonation, loss of N2, and reprotonation forms the product.

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 Why it is Important to Have More Than
One Way to Carry Out a Reaction

Catalytic hydrogenation reduces

aromatic nitro groups and carbonyl groups.

Wolff–Kishner reduction reduces

only the carbonyl group.

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 Substituents on a Benzene Ring Can Be
Chemically Changed

Bromine will selectively substitute for a benzylic hydrogen

in a radical substitution reaction.

A halogen at the benzylic position can lead to substitution or elimination.

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 Substitution at the Benzylic Position

SN1 and SN2 reactions can lead to a wide variety of substituted benzenes.

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 Elimination at the Benzylic Position

E1 and E2 reactions lead to alkene-substituted benzenes.

(A bulky base is used to encourage elimination over substitution.)

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 Unsaturated Substituents
Can Be Reduced

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 The Benzene Ring is Reduced Only
at High Temperature and Pressure

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 Alkyl Substituents are Oxidized
to Carboxyl Groups

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 Nitro Substituents are Reduced
by Catalytic Hydrogenation

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 Nomenclature of Disubstituted Benzenes

The relative positions of two substituents can be indicated

by numbers or by prefixes.

ortho = adjacent
meta = separated by one carbon
para = opposite one another

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 Nomenclature of Disubstituted Benzenes

• The substituents are listed in alphabetical order.

• The first substituent is given the 1-position.

• The ring is numbered to give the second substituent the lowest possible number.

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 The Effect of Substituents on Reactivity

• Substituents that donate electron density to the benzene ring increase

benzene’s nucleophilicity and stabilize the carbocation intermediate.

• Substituents that withdraw electron density to the benzene ring

decrease benzene’s nucleophilicity and destabilize the carbocation intermediate.

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 The Effect of Substituents on Orientation

When an electrophilic aromatic substitution reaction occurs on a

substituted benzene, where does the new substituent attach itself?

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 Activating substituents
donate electrons by
resonance.

Deactivating substituents
(except ammonium ions)
withdraw electrons inductively
and by resonance

Ammonium ions strongly

withdraw electrons inductively.

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 Ortho–Para Directors

• All activating substituents are ortho–para directors.

• Weakly deactivating substituents (halogens) are ortho–para directors.

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 Meta Directors

All moderately and strongly deactivating substituents are meta directors.

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 Which Carbocation Intermediate
is the Most Stable?

For substituents that donate electrons by resonance,

ortho or para substitution forms a relatively stable resonance contributor.
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 Which Carbocation Intermediate
is the Most Stable?

For substituents that donate electrons inductively,

ortho or para substitution forms a relatively stable resonance contributor.
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 Which Carbocation Intermediate
is the Most Stable?

For substituents that withdraw electrons,

ortho or para substitution forms a relatively unstable resonance contributor.
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 Halogenation with a
Strongly Activating Group Present
halogenation of a ring with a strongly activating substituent
does not require a catalyst

if a catalyst is used,
substitution occurs at all ortho and para positions

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 The Synthesis of Trisubstituted Benzenes

The directing effects of both substituents on a disubstituted benzene

must be considered in deciding where the third group will add.

Both substituents direct to equivalent positions.

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 The Synthesis of Trisubstituted Benzenes

Both substituents direct to equivalent positions.

Addition between two substituents is a minor product

because of steric hindrance.
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 The Synthesis of Trisubstituted Benzenes

Both substituents direct to different positions.

The strong activator wins out over the weak activator.

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 The Synthesis of Trisubstituted Benzenes

Both substituents direct to different positions.

The similar directing ability of the groups leads to
addition at both positions.
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