Chapter 17

Copyright © 2010 Pearson Education, Inc.

Organic Chemistry, 7th EditionL. G. Wade, Jr.

Reactions of Aromatic Compounds

Chapter 17 2

Electrophilic Aromatic Substitution

Although benzene’s pi electrons are in a stable aromatic system, they are available to attack a strong electrophile to give a carbocation.

This resonance-stabilized carbocation is called a sigma complex because the electrophile is joined to the benzene ring by a new sigma bond.

Aromaticity is regained by loss of a proton.

Chapter 17 3

Mechanism of Electrophilic Aromatic Substitution

Chapter 17 4

Bromination of Benzene

Chapter 17 5

Mechanism for the Bromination of Benzene: Step

1

Before the electrophilic aromatic substitution can take place, the electrophile must be activated.

A strong Lewis acid catalyst, such as FeBr3, should be used.

Br Br FeBr3 Br Br FeBr3+ -

(stronger electrophile than Br2)

Chapter 17 6

H

H

H

H

H

H

Br Br FeBr3

H

H

H

H

H

H

Br+ FeBr4

-

H

H

H

H

H

H

Br

FeBr4-

Br

H

H

H

H

H

+ FeBr3 + HBr

Step 2: Electrophilic attack and formation of the sigma complex.

Step 3: Loss of a proton to give the products.

Mechanism for the Bromination of Benzene: Steps

2 and 3

Chapter 17 7

Energy Diagram for Bromination

Chapter 17 8

Chlorination and Iodination

Chlorination is similar to bromination. AlCl3 is most often used as catalyst, but FeCl3 will also work.

Iodination requires an acidic oxidizing agent, like nitric acid, to produce iodide cation.

H+ + HNO3 + ½ I2 I+ + NO2 + H2O

Chapter 17 9

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

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.

Solved Problem 1

Solution

Chapter 17 10

Nitration of Benzene

Sulfuric acid acts as a catalyst, allowing the reaction to be faster and at lower temperatures.

HNO3 and H2SO4 react together to form the electrophile of the reaction: nitronium ion (NO2

+).

HNO3H2SO4

NO2

+ H2O

Chapter 17 11

Mechanism for the Nitration of Benzene

Chapter 17 12

Reduction of the Nitro Group

NO2

Zn, Sn, or Feaq. HCl

NH2

Treatment with zinc, tin, or iron in dilute acid will reduce the nitro to an amino group.

This is the best method for adding an amino group to the ring.

Chapter 17 13

Sulfonation of Benzene

Sulfur trioxide (SO3) is the electrophile in the reaction. A 7% mixture of SO3 and H2SO4 is commonly referred

to as “fuming sulfuric acid”. The —SO3H groups is called a sulfonic acid.

SO3H

+ SO3H2SO4

Chapter 17 14

Mechanism of Sulfonation

Benzene attacks sulfur trioxide, forming a sigma complex.

Loss of a proton on the tetrahedral carbon and reprotonation of oxygen gives benzenesulfonic acid.

Chapter 17 15

Desulfonation Reaction

Sulfonation is reversible. The sulfonic acid group may be removed from

an aromatic ring by heating in dilute sulfuric acid.

HSO3H

+ H2OH+, heat

+ H2SO4

Chapter 17 16

Mechanism of Desulfonation

In the desulfonation reaction, a proton adds to the ring (the electrophile) and loss of sulfur trioxide gives back benzene.

Chapter 17 17

Nitration of Toluene

Toluene reacts 25 times faster than benzene. The methyl group is an activator. The product mix contains mostly ortho and

para substituted molecules.

Chapter 17 18

Ortho and Para Substitution

Ortho and para attacks are preferred because their resonance structures include one tertiary carbocation.

Chapter 17 19

Energy Diagram

Chapter 17 20

Meta Substitution

When substitution occurs at the meta position, the positive charge is not delocalized onto the tertiary carbon, and the methyl groups has a smaller effect on the stability of the sigma complex.

Chapter 17 21

Alkyl Group StabilizationCH2CH3

Br2FeBr3

CH2CH3

Br

CH2CH3

Br

CH2CH3

Br

+ +

o-bromo(38%)

m-bromo(< 1%)

p-bromo(62%)

Alkyl groups are activating substituents and ortho, para-directors.

This effect is called the inductive effect because alkyl groups can donate electron density to the ring through the sigma bond, making them more active.

Chapter 17 22

Substituents with Nonbonding Electrons

Resonance stabilization is provided by a pi bond between the —OCH3 substituent and the ring.

Chapter 17 23

Meta Attack on Anisole

Resonance forms show that the methoxy group cannot stabilize the sigma complex in the meta substitution.

Chapter 17 24

Bromination of Anisole

A methoxy group is so strongly activating that anisole is quickly tribrominated without a catalyst.

Chapter 17 25

The Amino Group

Aniline reacts with bromine water (without a catalyst) to yield the tribromoaniline.

Sodium bicarbonate is added to neutralize the HBr that is also formed.

Chapter 17 26

Summary of Activators

Chapter 17 27

Activators and Deactivators

If the substituent on the ring is electron donating, the ortho and para positions will be activated.

If the group is electron withdrawing, the ortho and para positions will be deactivated.

Chapter 17 28

Nitration of Nitrobenzene

Electrophilic substitution reactions for nitrobenzene are 100,000 times slower than for benzene.

The product mix contains mostly the meta isomer, only small amounts of the ortho and para isomers.

Chapter 17 29

Ortho Substitution on Nitrobenzene

The nitro group is a strongly deactivating group when considering its resonance forms. The nitrogen always has a formal positive charge.

Ortho or para addition will create an especially unstable intermediate.

Chapter 17 30

Meta Substitution on Nitrobenzene

Meta substitution will not put the positive charge on the same carbon that bears the nitro group.

Chapter 17 31

Energy Diagram

Chapter 17 32

Deactivators and Meta- Directors

Most electron withdrawing groups are deactivators and meta-directors.

The atom attached to the aromatic ring has a positive or partial positive charge.

Electron density is withdrawn inductively along the sigma bond, so the ring has less electron density than benzene and thus, it will be slower to react.

Chapter 17 33

Ortho Attack of Acetophenone

In ortho and para substitution of acetophenone, one of the carbon atoms bearing the positive charge is the carbon attached to the partial positive carbonyl carbon.

Since like charges repel, this close proximity of the two positive charges is especially unstable.

Chapter 17 34

Meta Attack on Acetophenone

The meta attack on acetophenone avoids bearing the positive charge on the carbon attached to the partial positive carbonyl.

Chapter 17 35

Other Deactivators

Chapter 17 36

Nitration of Chlorobenzene

When chlorobenzene is nitrated the main substitution products are ortho and para. The meta substitution product is only obtained in 1% yield.

Chapter 17 37

Halogens Are Deactivators

X

Inductive Effect: Halogens are deactivating because they are electronegative and can withdraw electron density from the ring along the sigma bond.

Chapter 17 38

Halogens Are Ortho, Para-Directors

Resonance Effect: The lone pairs on the halogen can be used to stabilize the sigma complex by resonance.

Chapter 17 39

Energy Diagram

Chapter 17 40

Summary of Directing Effects

Chapter 17 41

Effect of Multiple Substituents

The directing effect of the two (or more) groups may reinforce each other.

Chapter 17 42

Effect of Multiple Substituents (Continued)

The position in between two groups in Positions 1 and 3 is hindered for substitution, and it is less reactive.

Chapter 17 43

Effect of Multiple Substituents (Continued)

OCH3

O2N

Br2FeBr3

OCH3

O2N

Br

OCH3

O2N

Br

If directing effects oppose each other, the most powerful activating group has the dominant influence.

major products obtained

Chapter 17 44

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.

Chapter 17 45

Mechanism of the Friedel–Crafts Reaction

Step 1

Step 2

Step 3

Chapter 17 46

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.

Chapter 17 47

Alcohols and Lewis Acids

Alcohols can be treated with BF3 to form the carbocation.

Chapter 17 48

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.

Chapter 17 49

Rearrangements

Chapter 17 50

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

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.

Solved Problem 2

Solution

Chapter 17 51

Friedel–Crafts Acylation

Acyl chloride is used in place of alkyl chloride. The product is a phenyl ketone that is less

reactive than benzene.

Chapter 17 52

Mechanism of Acylation

Step 1: Formation of the acylium ion.

Step 2: Electrophilic attack to form the sigma complex.

Chapter 17 53

Clemmensen Reduction

The Clemmensen reduction is a way to convert acylbenzenes to alkylbenzenes by treatment with aqueous HCl and amalgamated zinc.

Chapter 17 54

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.

Chapter 17 55

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.

Chapter 17 56

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.

Chapter 17 57

Benzyne Reaction: Elimination-Addition

Reactant is halobenzene with no electron-withdrawing groups on the ring.

Use a very strong base like NaNH2.

Chapter 17 58

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.

Chapter 17 59

Nucleophilic Substitution on the Benzyne Intermediate

Chapter 17 60

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

Chapter 17 61

Catalytic Hydrogenation

Elevated heat and pressure is required. Possible catalysts: Pt, Pd, Ni, Ru, Rh. Reduction cannot be stopped at an

intermediate stage.

CH 3

CH 3Ru, 100°C

1000 psi3 H 2,

CH 3

CH 3

Chapter 17 62

Birch Reduction

H

H

H

H

H

HNa or Li

NH3 (l), ROH

H

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.

Chapter 17 63

Mechanism of the Birch Reduction

Chapter 17 64

Limitations of the Birch Reduction

Chapter 17 65

Side-Chain Oxidation

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.

CH2CH3

(or Na2Cr2O7, H2SO4 , heat)

CO2HKMnO4, NaOHH2O, 100oC

Chapter 17 66

Side-Chain Halogenation

CH2CH3 Br2 or NBS

h

CHCH3

Br

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.

Chapter 17 67

Mechanism of Side-Chain Halogenation

Chapter 17 68

SN1 Reactions

Benzylic carbocations are resonance-stabilized, easily formed.

Benzyl halides undergo SN1 reactions.

CH 2BrCH3CH2O H, heat

CH2O CH 2CH3

Chapter 17 69

SN2 Reactions

Benzylic halides are 100 times more reactive than primary halides via SN2.

The transition state is stabilized by a ring.

Chapter 17 70

Oxidation of Phenols

Na2Cr2O7 H2SO4

OH

Cl

O

Cl

O2-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.