1

CHAPTER 12

Substituted Benzene

12.1 Alkylbenzenes (Ar-R)

Bezylic carbons:

CH3 CH2CH3CH(CH3)2

2

Reactions of Alkylbenzens

1. Free Radical Halogenation

CH2CH3Br2

hvCHCH3

Br

3

2 -Oxidation RKMnO4hot

CO2H

CH3 KMnO4hot

CO2HCH2CH3

hotMnO4

-

CO2H

CHCH3

CH2CH3

hotMnO4

- CO2H

4

Notice: CCH3

CH3

CH3 hotMnO4

-

Benzylic carbon has no hydrogen

No Reaction

CH3

CH3hotMnO4

- CO2H

HO2C

hotMnO4

- CO2H

CO2H

5

Phenols (ArOH)

OH

A phenol has a hydroxyl group directly attached to the benzene ring

SP2- hybridized carbon

C---O bond is not easily broken No substitution or elimination reaction

R-OH + HBr RBr + H2O SN1 or SN2

Ar-OH + HBr No reaction

6

Acidity of Phenols

CH3CH2OH + NaOH CH3CH2O- Na++ H2O Not favored

pKa= 16 pKa=15.7

OH + NaOH O- Na+ + H2O favored

pKa= 10pKa= 15.7

O- + R X OR+ X-

SN2

a phenoxide ion

7

Esterfication of phenols

OH + CH3C

O

OCCH3

O

OCCH3

O

+ CH3CO2H

8

The Kolbe Reaction

OH

1) OH-2) CO2

3) H+

OH

CO2H

Mechanism

OHOH- O-

C OO+ -

O

H

C OO-

OH

CO2-

H+OH

CO2HSalicylic acid

9

Importance of Kolbe Reaction

To Synthesize aspirin

OH

CO2H

CH3COCCH3

O O

+CO2H

OCCH3

O

Acetylsalicylic acid

(Aspirin)

10

The Reimer-Tiemann Reaction

The reaction of phenol with chloroform in the presence of base.

OH1) CHCl3, OH-, 70

2) H2O, H+

C

OH

CHO

Salicylaldehyde

11

Mechanism:

OH- H CCl3- H2O

+CCl3

Cl-CCl2

dichlorocarbene

CCl2O-+ O

HCCl2..

O-

CHCl2

OH-

O-

CHClO

H

O-

H

O

H+

OH

H

O

12

Oxidation of phenols: phenol resists oxidation

Oxidation of hydroquinones (1,4-dimethoxy benzenes)OH

OH

O

O

+ 2 H++ 2e-

O

H

hydroquinone1.4-benzoquinone

(quinone)

O

H

OH

OH

O

H

O

O

+ 2 H++ 2e-

1.2-benzoquinone

13

Preparation of Aniline

HNO3

H2SO4

NO2

NO2Fe, HCl N+H3Cl- OH- NH2

H2, Pd/C or Pt

14

Benzenediazonium Salts

NH2NaNO2, HCl, 0

OC N N Cl-+

+ H2O

benzenediazonium chloride

very reactive Excellent leaving abilty of N2 gas

N N+ _ N2+

Nu -Nu

15

Reactions of benzenediazinium Salts

NH2NaNO2, HCl,

0OC

Cl

CuCl

Br

CuBr

CN

CuCN, KCN

IKI

F

1) HBF4

2) heat

OH

H2O, H+

H

H3PO2

HNO3, H2SO41)

2) H2, Pt

N N Cl-+

16

Coupling reactions

N N+

N N+

N N+

OH N N OH+

CO2H

NH2

N N

CO2H

+ NHCH3+ N N NHCH3

NaNO2, HCl, 0 CO

Azo compound

17

Synthesis involving diazonium salts

CH3 C NCH3? ? ? ?

HNO3, H2SO4

CH3 NO2

1) Fe, HCl

2) OH-

CH3 NH2

NaNO2,

HCl, O CO

CH3 N2+ Cl-

CuCN, KCN

18

Nucleophilic Aromatic Substitution

X Nu - No SN1 or SN2 reaction+

X Nu -+ Nu + X-But

Nucleophilic Aromatic Substitution

19

Examples

Cl10% NaOH

350 300 atmo OH

O2N Cl 10% NaOH

160o

O2N OH

P-nitrophenol

O2N Cl

NO2

NO2

H2Owarm

O2N OH

NO2

NO2

increasingreactivitytoward Nu -

20

Other nucleophiles

O2N Cl

NO2NH3

heat

O2N Cl

NO2CH3CH2S-

heat

O2N NH2

NO2

O2N SCH2CH3

NO2

21

Carbanion Mechanism:If the ring is activated toward nucleophilc substitution by an electron withdrawing group (I,e NO2)

Two steps 1) addition of Nu: to form carbanion

2 (Loss of the halide ion

O2N Clslow

OH-

O2NCl

OH

-

O2N OH

Carbanion intermediate

fast

22

Carbanion intermediate is stabilized by resonance

O2NCl

OH OH

ClN

O

O-

+

NO-

O-

OH

Cl+

OH

ClN

O

O-

+

23

Benzyne Mechanism:

If there is no electron withdrawing substituent on the ring.

ClNH2

-, NH3NH2

Cl

H NH2-

- HClNH2

- NH2

NH3

NH2NH2-

+

Mechanism

Benzyne

24

Benzyne

HH

H

H

25

Syntheses of substituted benzene compounds

• How would you synthesize

• But IF YOU START WITH CHLORINATION

Cl

NO2

HNO3

H2SO4 NO2

Cl

NO2

Cl2FeCl3

Cl

Cl2

FeCl3

HNO3

H2SO4

Cl

NO2

ClNO2

+

o,p-director

26

SynthesesBr

NH2

? ? ?

HNO3H2SO4

NO2

Br2, FeBr3

NO2

Br

1) Fe, HCl

2) OH-

27

Note: Nitro group can be converted to arylamines which in turn can also be converted to aryldiazonium salts,=> making a diversity of substituted products

NO2

1) Fe, HCl

2) OH-NH2

NaNO2, HCl0o

N2+

Nu

Nu

m-director o,p-directoreasily displaced

Notice: Amino group does not undergo Friedel-Crafts reaction because an amino group reacts with Lewis acid since it is basic to form strongly deactivating grouo

NH2+

AlCl3N+H2

Al-Cl3

strongly deactivating

28

Nitrobenzene does not undergo Friedel-Crafts reactions

NO2

RX or RCXO

AlX3No aromatic substitution

Notice: An amino group is o,p-director, but an ammonium group ( -NR3

+) is an m-director and deactivating.

NH2 HNO3+ N+H3 NO3-

o,p-director m-director

29

Sulfonic acid group (-SO3H)

The sulfonic acid group is easily removed and can be displaced by a

variety of reagents.

SO3HH2O, H+ H2SO4+

SO3H OH1) Fused NaOH

2) H2O, H+

30

OHBr? ? ?

Br2, FeBr3

Br

HNO3H2SO4

NO2Br 1) Fe, HCl

2) OH-NH2Br NaNO2,HCl

0oN2

+Br

H2O, H+

31

Br

Br? ? ?

HNO3H2SO4

NO2

Br2, FeBr3

NO2

Br1) Fe, HCl

2) OH- NH2

BrNaNO2,HCl

0N2

+

Br

CuBr

32

CO2H

NH2

? ? ? ?

CH3CH2Cl,AlCl3

CH2CH3

HNO3, H2SO4

CH2CH3

NO2

1) Fe, HCl

2) OH- CH2CH3

NH2

KMnO4

heat

33

OCH3? ? ? ?

NO2

HNO3, H2SO4

NH2

H2,Pd/C

1) NaNO2,HCl

2) H2O, H+

OH

NaOH

O-

CH3I

34

CH3

Cl

CO2H

? ? ? ?

KMno4, heat

CO2H

Cl2, FeCl3

35

HNO3, H2SO4

O2N

CH3

H2N

CH3

H2,Pd/C

1) Cl2, FeCl3

2) NaNO2, HCl

Cl- N2+

CH3

Cl

CH3

Cl

CH3

? ? ? ?

H3PO2