17.1 Mechanism for Electricphilic Aromatic Substitution

Chapter 17 Chapter 17 pp

A ti S b tit ti

Aromatic Substitution Reactions

Reactions

OrgChem- 1

17.1 Mechanism for Electricphilic Aromatic Substitution

Arenium ion

resonance stabilization

Substitution

resonance stabilization

Example 1.

Example 2 Example 2.

OrgChem- 3

Example 2. Mechanism of the nitration of benzene

Addition reaction vs.

Electrophilic aromatic substitution Electrophilic aromatic substitution

OrgChem- 5

<

Stability

<

E

H E

<

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

Is the addition reaction possible for a benzene ? p

Very difficult because of the stability of the product

E

resonance stabilization

OrgChem- 7

17.2 Effect of Substituent

17 times faster than the substitution of benzenet es aste t a t e subst tut o o be e e

Why ?

Resonance stabilization

Ortho attack

Meta attack

Para attack

M t d tt k i f d

OrgChem-Chap17 9

Meta and para attack is favored

CH₃ is an ortho/para directing group

Nitration of anisole (methoxy benzene)

10,000 times faster than the substitution of benzene

Wh ?

R t bili ti

Why ?

Resonance stabilization

The effect of methoxy group

1.Inductive effect,

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

2. Resonance effect →explanation is possiblep p

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

,

electrons is the ortho/para director

OrgChem- 11

Nitration of nitrobenzene

1. 10¹⁷ times slower than the substitution of benzene

benzene

2. meta director

OrgChem- 13

Until now,

Activating group (elecron donating group): ortho/para director Deactivationg group (elecron withdrawing group): meta

dircectot dircectot

Exception: Halogens,

th / d t d ti ti

ortho/para derector + deactivating group

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

F is highly electronegative, therefore

F

g y g

inductive withdrawing effect is stronger than the resonance effect

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

Cl, Br, I

g enough as the methoxy

Because the overlapping netween 2p AO 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 there is the resonance effect although it is much weaker.

OrgChem- 15

Nose ring theory !

Accurate experiment results are most important !

@

Two ortho positions and one para Two ortho positions and one para

position, therefore statistically the ratio or ortho to para products should be 2 to 1,p p ,

Which is generally true! (nitration of toluene)

toluene)

OrgChem- 17

See P 680

17.3 Effect of Multiple Substituent

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

R l

Rule:

17.4 Nitration

OrgChem- 19

Preparation of NO₂⁺

A problem occurs with amino substitution

N with unpaired electrons looks like a activating group and o/p 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!

activating group) conc. is very low, 18% is para product!

OrgChem- 21

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

Example,

17.5 Halogenation

Mechanism

Same as the nitration Same as the nitration Resonance stabiliztion,

Activating group faciliate the reaction

Cl

+ AlCl + HCl

OrgChem-Chap17 23

Activating group faciliate the reaction + AlCl₃ + HCl

17.6 Sulfonation

Fuming sulfuric acid

OrgChem- 25

Mechanism

17.7 Friedel-Craft Alkylation

OrgChem- 27

Mechanism of the Friedel-Craft Alkylation

Drawbacks

1. The alkyl groups that is added to the ring is an

activated group: a large amount of products w/ two lk l

or more alkyl groups

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

3. Rearrangementg

CH₃CH₂CH₂CH₂Cl + AlCl₃ CH₃CH₂CH₂CH₂ AlCl₄

Because

OrgChem- 29

CH₃CH₂CHCH₃

Because

Other ways to generate carbocations

Strong acid TsOH can eliminate water Strong acid, TsOH, can eliminate water, then CH₃-ph-CH₂⁺ can be generated

Other examples Lewis acid is used

Synthetic detergents

OrgChem- 31

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

17.8 Friedel-Craft Acylation

Generation of acyl cation

OrgChem- 33

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

Examples Examples

Examples

OrgChem- 35

17.9 Electrophilic Substitution of Polycyclic Aromatic Compounds Polycyclic Aromatic Compounds

Why the 1 position is preferred?

Containing

stable benzene ring

Containing stable

stable

benzene ring

OrgChem- 37

17.10 Nucleophilic Aromatic

Substitution; Diazonium ion

Substitution; Diazonium ion

Examples

OrgChem- 39

17.11 Nucleophilic Aromatic S

Substitution; Addition-Elimination

Mechanism

OrgChem- Not S_N2 but Addition-Elimination 41

The order of leaving group ability

Examples

17.12 Nucleophilic Aromati Substitution;

Elimination-Addition Elimination-Addition

When there is no electron withdrawing group at o/p

iti th li i ti dditi ith

position, then elimination-addition occurs with very strong base (amide anion) or with weak base at high temperature

temperature

OrgChem- 43

Mechanism

Benzyne

The existence of benzyne

OrgChem- 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 SnCl₂)

H₃CH₂COC O

NH₂

Cl

Application

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

a methylene group

1. Clemmenson reduction

reduction

2. Wolff-Kishner reduction

3. Catalytic hydrogenation

OrgChem- 47

H₂₂/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

Oxidation of alkyl groups bonded to the aromatic ring

If the carbon bonded to the ring is not tertiary

17.14 Synthesis of Aromatic Compound

OrgChem- 49

Preparation of m-chlorobenzene and p-chlorobenzene

Preparation of o-bromophenol

HO HO

HO

+ Br₂

HO HO

Br

+ Mixuture

Br

Preparation of m-bromochlorobenzene

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

S O

Solution: use NO₂, a m director

Preparation of m-bromotoluene

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

Solution: use NO₂, the m director

OrgChem- 51

Preparation of m-butylbenzenesulfonic acid

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

Preparation of

OrgChem- bezene53