Organic Chemistry, 7th Edition

L. G. Wade, Jr.

Chapter 17
Reactions of Aromatic Compounds
Class 3
Effect of Multiple Substituents

▪ The directing effect of the two (or more)

groups may reinforce each other.

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 Effect of Multiple Substituents

▪ The position in between two groups in

Positions 1 and 3 is hindered for substitution,
and it is less reactive.

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 Effect of Multiple Substituents
OCH3 OCH3 OCH3
Br
Br2
FeBr3
O2N O2N O2N
Br

major products obtained

▪ If directing effects oppose each other, the

most powerful activating group has the
dominant influence.

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 Solved Problem 1
Predict the major product(s) of bromination of p-chloroacetanilide.

Solution
The amide group (–NHCOCH3) is a strong activating and directing group because the nitrogen atom
with its nonbonding pair of electrons is bonded to the aromatic ring. The amide group is a stronger
director than the chlorine atom, and substitution occurs mostly at the positions ortho to the amide. Like
an alkoxyl group, the amide is a particularly strong activating group, and the reaction gives some of
the dibrominated product.

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 Friedel–Crafts Alkylation

▪ Synthesis of alkyl benzenes from alkyl halides

and a Lewis acid, usually AlCl3.

▪ Reactions of alkyl halide with Lewis acid

produces a carbocation, which is the
electrophile.
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 Mechanism of the Friedel–Crafts
Reaction

Step 1

Step 2

Step 3

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 Protonation of Alkenes

▪ An alkene can be protonated by HF.

▪ This weak acid is preferred because the

fluoride ion is a weak nucleophile and will not
attack the carbocation.
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 Alcohols and Lewis Acids

▪ Alcohols can be treated with BF3 to form the

carbocation.

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 Limitations of Friedel–Crafts

▪ Reaction fails if benzene has a substituent

that is more deactivating than halogens.

▪ Rearrangements are possible.

▪ The alkylbenzene product is more reactive

than benzene, so polyalkylation occurs.

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Rearrangements

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 Solved Problem 2
Devise a synthesis of p-nitro-t-butylbenzene from benzene.

Solution
To make p-nitro-t-butylbenzene, we would first use a Friedel–Crafts reaction to make t-butylbenzene.
Nitration gives the correct product. If we were to make nitrobenzene first, the Friedel–Crafts reaction
to add the t-butyl group would fail.

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 Friedel–Crafts Acylation

▪ Acyl chloride is used in place of alkyl chloride.

▪ The product is a phenyl ketone that is less
reactive than benzene.
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 Mechanism of Acylation

Step 1: Formation of the acylium ion.

Step 2: Electrophilic attack to form the sigma complex.

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 Clemmensen Reduction

▪ The Clemmensen reduction is a way to

convert acylbenzenes to alkylbenzenes by
treatment with aqueous HCl and
amalgamated zinc.

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Nucleophilic Aromatic Substitution

▪ A nucleophile replaces a leaving group on the

aromatic ring.
▪ This is an addition–elimination reaction.
▪ Electron-withdrawing substituents activate the
ring for nucleophilic substitution.
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 Mechanism of Nucleophilic
Aromatic Substitution
Step 1: Attack by hydroxide gives a resonance-stabilized complex.

Step 2: Loss of chloride gives the product. Step 3: Excess base deprotonates the product.

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 Activated Positions

▪ Nitro groups ortho and para to the halogen

stabilize the intermediate (and the transition
state leading to it).
▪ Electron-withdrawing groups are essential for
the reaction to occur.
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 Benzyne Reaction:
Elimination-Addition

▪ Reactant is halobenzene with no electron-

withdrawing groups on the ring.
▪ Use a very strong base like NaNH2.
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 Benzyne Mechanism

▪ Sodium amide abstract a proton.

▪ The benzyne intermediate forms when the bromide is
expelled and the electrons on the sp2 orbital adjacent
to it overlap with the empty sp2 orbital of the carbon
that lost the bromide.
▪ Benzynes are very reactive species due to the high
strain of the triple bond.

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Nucleophilic Substitution on the
Benzyne Intermediate

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 Chlorination of Benzene

▪ Addition to the
benzene ring may
occur with excess of
chlorine under heat
and pressure.

▪ The first Cl2 addition is

difficult, but the next
two moles add rapidly. An insecticide

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 Catalytic Hydrogenation
CH3
CH 3

3 H 2 , 1000 psi
Ru, 100°C
CH 3
CH3

▪ Elevated heat and pressure is required.

▪ Possible catalysts: Pt, Pd, Ni, Ru, Rh.
▪ Reduction cannot be stopped at an
intermediate stage.
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 Birch Reduction
H H H
H H H H
Na or Li
NH3 (l), ROH
H H H H
H H H

▪ This reaction reduces the aromatic ring to a

nonconjugated 1,4-cyclohexadiene.
▪ The reducing agent is sodium or lithium in a
mixture of liquid ammonia and alcohol.

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Mechanism of the Birch Reduction

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Limitations of the Birch Reduction

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 Side-Chain Oxidation
CH2CH3 CO2H
KMnO4, NaOH
H2O, 100oC

(or Na2Cr2O7, H2SO4 , heat)

▪ Alkylbenzenes are oxidized to benzoic acid by

heating in basic KMnO4 or heating in
Na2Cr2O7/H2SO4.
▪ The benzylic carbon will be oxidized to the carboxylic
acid.

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 Side-Chain Halogenation

Br
CH2CH3 CHCH3
Br2 or NBS
h

▪ The benzylic position is the most reactive.

▪ Br2 reacts only at the benzylic position.
▪ Cl2 is not as selective as bromination, so
results in mixtures.

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Mechanism of Side-Chain
Halogenation

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 SN1 Reactions

▪ Benzylic carbocations are resonance-

stabilized, easily formed.
▪ Benzyl halides undergo SN1 reactions.

C H 3 C H 2 O H , h eat
C H 2B r C H 2O C H 2C H 3

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 SN2 Reactions

▪ Benzylic halides are

100 times more
reactive than
primary halides via
SN2.

▪ The transition state

is stabilized by a
ring.

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 Oxidation of Phenols
OH O
Cl Cl
Na2Cr2O7
H2SO4

O
2-chloro-1,4-benzoquinone

▪ Phenol will react with oxidizing agents to produce

quinones.
▪ Quinones are conjugated 1,4-diketones.
▪ This can also happen (slowly) in the presence of air.

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