OrgChem Chap17

Chapter 17

Aromatic Substitution Reactions

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OrgChem Chap17

17.1

Mechanism for Electricphilic Aromatic Substitution

Arenium ion resonance stabilization

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Example 1.

Example 2.

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OrgChem Chap17

Example 2. Mechanism of the nitration of benzene

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Addition reaction vs.

Electrophilic aromatic substitution

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OrgChem Chap17

<

Stability

<

E H E

<

 Ga <  Gs

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

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OrgChem Chap17

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

OrgChem Chap17

17 times faster than the substitution of benzene

Why ? Resonance stabilization

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Ortho attack Meta attack

OrgChem-Chap17

Para attack Meta and para attack is favored CH 3

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is an ortho/para directing group

Nitration of anisole (methoxy benzene) 10,000 times faster than the substitution of benzene Why ?

Resonance stabilization

OrgChem Chap17 10

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.

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

OrgChem Chap17 11

Nitration of nitrobenzene

OrgChem Chap17

1. 10 17 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

OrgChem Chap17

1. 17 times slower than the substitution of benzene 2. ortho/para director

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OrgChem Chap17 F

F 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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OrgChem Chap17 @

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) 16

OrgChem Chap17

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

OrgChem-

controls the regiochemistry!

Chap17 18

17.4

Nitration

OrgChem Chap17 19

Preparation of NO 2 +

OrgChem Chap17 20

A problem occurs with amino substitution 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!

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

OrgChem Chap17 22

17.5

Halogenation

Mechanism Same as the nitration Resonance stabiliztion, Activating group faciliate the reaction

OrgChem-Chap17 Cl

+ AlCl 3 + HCl

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17.6

Sulfonation

OrgChem Chap17

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

OrgChem Chap17

Because

CH 3 CH 2 CH 2 CH 2 Cl + AlCl 3 CH 3 CH 2 CH 2 CH 2 AlCl 4 CH 3 CH 2 CHCH 3 29

Other ways to generate carbocations Strong acid, TsOH, can eliminate water, then CH 3 -ph-CH 2 + can be generated Other examples Lewis acid is used

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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

OrgChem Chap17

Why the 1 position is preferred?

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OrgChem Chap17

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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Not S N 2 but Addition-Elimination

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Examples

OrgChem Chap17

The order of leaving group ability

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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

OrgChem Chap17 45

17.13

Some Additional Useful Reactions

Reduction of nitro group to amine using hydrogen and a catalyst or by using acid and a metal (Fe, Sn, or SnCl 2 )

O H 3 CH 2 COC NH 2 Cl OrgChem Chap17

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

OrgChem Chap17 47

H 2 /Pt reduction vs Wolff-Kishner and Clemmenson reduction

-

H 2 /Pt works for the carbonyl attached to the aromatic ring

-

Wolff-Kishner and Clemmenson reduction do not have this restriction Oxidation of alkyl groups bonded to the aromatic ring

OrgChem Chap17

If the carbon bonded to the ring is not tertiary

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17.14

Synthesis of Aromatic Compound

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Preparation of m-chlorobenzene and p-chlorobenzene Preparation of o-bromophenol

HO HO + Br 2 Br + HO Br Mixuture OrgChem Chap17 50

OrgChem Chap17

Preparation of m-bromochlorobenzene

Problem: both chloro and bromo groups are o/p directors Solution: use NO 2 , a m director

Preparation of m-bromotoluene

Problem: methyl group is an o/p director Solution: use NO 2 , the m director

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OrgChem Chap17

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

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