Chapter 16: Reactions of Substituted Benzenes

Nomenclature of Substituted Benzenes:

In disubstituted benzenes, the relative positions of the
two substituents are indicated by numbers or by prefixes (o; m;
p):

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Substituted benzenes undergo the five electrophilic
aromatic substitution reactions discussed in Chapter 15:

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Reactions of Substituted Benzenes: Effects of Substituents on
Reactivity and Orientation
The slow step of an electrophilic aromatic substitution reaction
is the formation of the carbocation intermediate:

The nature of groups already on an aromatic ring affect both

the reactivity and orientation of future substitution.

Reactivity:
•Electron-donating substituents (Activating groups) increase the
rate of substitution reactions by stabilizing the carbocation
intermediate. Activating groups cause the aromatic ring to be
more reactive than benzene.
•All activating groups are also ortho-para directors.

p- o-
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•Electron-withdrawing substituents (Deactivating groups)
decrease the rate of substitution reactions by destabilizing
the carbocation intermediate. Deactivating groups cause the
aromatic ring to be less reactive than benzene.
•Deactivating Groups are Meta Directors

m-

Electron Donation and Electron Withdrawal occur by:

Resonance
Inductive (sigma-bond)
Hyperconjugation

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 Resonance Electron Donation and Withdrawal
Substituents such as NH2 (NHR, NR2), OH (OR) donate electrons
by resonance, but they also withdraw electrons inductively
(Electron donation into the benzene ring by resonance is more
significant than inductive electron withdrawal from the ring)

These groups are ortho,para-directing substituent

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An ortho,para-directing substituent:

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Resonance donation into the benzene ring competes with
resonance donation into the carbonyl. These substituents are
less effective in donating electrons into the ring because…

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Substituents such as C=O, CΞN, SO3H, and NO2
withdraw electrons by resonance: These groups
are m-directors.

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Halogens withdraw electrons inductively more strongly than
they donate electrons by resonance: O-; p- deactivators

These substituents withdraw electrons both inductively

and by resonance:

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These substituents are powerful electron-withdrawing groups:
Except for the ammonium ions, these substituents withdraw
electrons both inductively and by resonance.

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All activating substituents are ortho–para directors:

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 The Effect of Substituents on pKa

Electron-withdrawing groups stabilize a base and therefore

increase the strength of its conjugate acid
Electron-donating groups destabilize a base and thus
decrease the strength of its conjugate acid

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 The more electronic deficient a substituent on phenol, the
stronger the acid:

To understand the relative pKa values, consider the

delocalization of the phenolate anion (stars show anion
distribution):

Unstable

More stable anion =

lower pKa Stable: “through resonance”
of anion into nitro

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The more electronic deficient a substituent on benzoic acid,
the stronger the acid:

Substituent effect on pKa is minimal in benzoic acids because

only inductive electronic effects are present:
The more electronic deficient a substituent on a protonated
aniline, the stronger the acid:

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The ortho–para product ratio decreases with an increase
in the size of the substituents:

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Methoxy and hydroxy substituents are so strongly activating
that halogenation is carried out without a Lewis acid:

A benzene ring with a meta director cannot

undergo a Friedel–Crafts reaction:

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In designing a disubstituted benzene, consider the order of
substitution:

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The Friedel–Crafts acylation must be carried out first, because
the nitro group is strongly deactivating:

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In the synthesis of para-chlorobenzoic acid from toluene,
the methyl group is oxidized after chlorination:

In the synthesis of meta-chlorobenzoic acid, the methyl

group is oxidized before chlorination:

How is the meta derivative prepared?

Friedel–Crafts acylation-Sulfonation-Carbonyl reduction
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 Synthesis of Trisubstituted Benzenes

Steric hindrance makes the position between the

substituents less accessible

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A strongly activating substituent will win out over a weakly
activating substituent or a deactivating substituent

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 Synthesis of Substituted Benzenes Using Arenediazonium
Salts : Preparation of the Diazonium Salt

Mechanism: See the Textbook

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 Nucleophilic Aromatic Substitution Reactions
Nucleophilic aromatic substitution reactions require at least
one strongly electron-withdrawing substituent to occur:

Electron-withdrawing substituents increase the reactivity of the

benzene ring toward nucleophilic substitution and decrease the
reactivity of the benzene ring toward electrophilic substitution
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The electron-withdrawing substituents must be ortho or para to
the site of nucleophile attack,

so that electrons of the attacking nucleophile can be

delocalized into these substituents
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The incoming group has to be a stronger base than the
group that is being replaced:

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