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Chapter 17Chapter 17

Aromatic Substitution Reactions

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Arenium ion

resonance stabilization

17.1 Mechanism for Electricphilic Aromatic Substitution

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Example 1.

Example 2.

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Example 2. Mechanism of the nitration of benzene

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Addition reaction vs.Electrophilic aromatic substitution

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H E

<

<

<

E

Stability

Ga < Gs Bezene is very stable so it is very diificult to break the resonance stabilization

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Is the addition reaction possible for a benzene ?

Very difficult because of the stability of the product

E

resonance stabilization

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17.2 Effect of Substituent

17 times faster than the substitution of benzene

Why ?

Resonance stabilization

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Ortho attack

Meta attack

Para attack

Meta and para attack is favored

CH3 is an ortho/para directing group

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Nitration of anisole (methoxy benzene)

10,000 times faster than the substitution of benzene

Why ? Resonance stabilization

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Therefore, any group that has an unshared pair of electrons is the ortho/para director

The effect of methoxy group

1.Inductive effect,

then as the oxygen is electronegative Methoxy is deactivating group not true

2. Resonance effect explanation is possible

This is what scientists are doing, you also should have this attitude, then find reasons. Otherwise no result at all.

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Nitration of nitrobenzene

1. 1017 times slower than the substitution of benzene

2. meta director

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Until now,

Activating group (elecron donating group): ortho/para director

Deactivationg group (elecron withdrawing group): meta dircectot

Exception: Halogens,

ortho/para derector + deactivating group

1. 17 times slower than the substitution of benzene

2. ortho/para director

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FF is highly electronegative, therefore inductive withdrawing effect is stronger than the resonance effect

Cl, Br, I

Cl, Br, and I are not very electronegative, while the resonance effect is not strong enough as the methoxy

Because the overlapping netween 2p AO of carbon and 3p(Cl), 4p(Br), 5p(I) AOs are not good. (2p AO for oxygen)

Still halogens are ortho/para director because there is the resonance effect although it is much weaker.

Nose ring theory !

Accurate experiment results are most important !

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@

Two ortho positions and one para position, therefore statistically the ratio or ortho to para products should be 2 to 1,

Which is generally true! (nitration of toluene)

Steric effect !

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See P 680

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17.3 Effect of Multiple Substituent

Methyl group controls the regiochemistry, because methyl group is a strong activating group

Rule: Groups that are closer to the top of Table 17.1 controls the regiochemistry!

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17.4 Nitration

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Preparation of NO2+

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N with unpaired electrons looks like a activating group and o/p director. But under acidic condition it can be protonated, then deactivating group and m director. Although the amine (strong activating group) conc. is very low, 18% is para product!

A problem occurs with amino substitution

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Amide group: much less basis, still activator and o/p director

Example,

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17.5 Halogenation

Same as the nitration

Resonance stabiliztion,

Activating group faciliate the reaction

Cl

+ AlCl3 + HCl

Mechanism

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17.6 Sulfonation

Fuming sulfuric acid

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Mechanism

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17.7 Friedel-Craft Alkylation

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Mechanism of the Friedel-Craft Alkylation

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Drawbacks

1. The alkyl groups that is added to the ring is an activated group: a large amount of products w/ two or more alkyl groups

2. Aromatic compound w/ strongly deactivating groups cannot be alkylated.

3. Rearrangement

CH3CH2CH2CH2Cl + AlCl3 CH3CH2CH2CH2 AlCl4

CH3CH2CHCH3

Because

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Other ways to generate carbocations

Other examples

Lewis acid is used

Strong acid, TsOH, can eliminate water,

then CH3-ph-CH2+ can be generated

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Synthetic detergents

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BHT and BHA are anti oxidant added to food prepared by Friedel-Crafts alkylation reactions

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17.8 Friedel-Craft Acylation

Generation of acyl cation

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Drawback: like the alkylation, this reaction does not work with strongly deactivated substrates (m directors)

Examples

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Examples

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17.9 Electrophilic Substitution of Polycyclic Aromatic Compounds

Why the 1 position is preferred?

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Containing stable benzene ring

Containing stable benzene ring

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17.10 Nucleophilic Aromatic Substitution; Diazonium ion

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Examples

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17.11 Nucleophilic Aromatic Substitution; Addition-Elimination

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Mechanism

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The order of leaving group ability

Examples

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17.12 Nucleophilic Aromati Substitution; Elimination-Addition

When there is no electron withdrawing group at o/p position, then elimination-addition occurs with very strong base (amide anion) or with weak base at high temperature

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Mechanism

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Benzyne

The existence of benzyne

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17.13 Some Additional Useful ReactionsReduction of nitro group to amine using hydrogen and a catalyst or by using acid and a metal (Fe, Sn, or SnCl2)

H3CH2COCO

Cl

NH2

Application

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Reduction of carbonyl group (aldehyde or ketone) to a methylene group

1. Clemmenson reduction

2. Wolff-Kishner reduction

3. Catalytic hydrogenation

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Oxidation of alkyl groups bonded to the aromatic ring

If the carbon bonded to the ring is not tertiary

H2/Pt reduction vs Wolff-Kishner and Clemmenson reduction

-H2/Pt works for the carbonyl attached to the aromatic ring

-Wolff-Kishner and Clemmenson reduction do not have this restriction

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17.14 Synthesis of Aromatic Compound

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Preparation of o-bromophenol

Preparation of m-chlorobenzene and p-chlorobenzene

HO

+ Br2

HO HO

Br

Br

+ Mixuture

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Preparation of m-bromochlorobenzene

Problem: both chloro and bromo groups are o/p directors

Solution: use NO2, a m director

Preparation of m-bromotoluene

Problem: methyl group is an o/p director

Solution: use NO2, the m director

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Preparation of m-butylbenzenesulfonic acid

Benzene sulfonic acid cannot be alkylated because the Friedel-Craft alkyl- or acylation does not work with deactivating group

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Preparation of

bezene