chapter 13 hofmann rearrangement by, g.deepa

CHAPTER 13

Hofmann Rearrangement

BY,

G.DEEPA

The Hofmann Rearrangement

Treatment of amides with bromine in basic solutiongives an amine with loss of the carbonyl carbon.

RCNH2

OBr2

HO–RNH2 + CO3

2–

Examples

(94%)

(CH3)3CCH2CNH2

OBr2, NaOH

H2O(CH3)3CCH2NH2

Br

CNH2

OBr2, KOH

H2O

Br

NH2

(87%)

Mechanism of the Hofmann Rearrangement

•The Hofmann rearrangement involves 6 steps in 3 stages.• 1.  formation of an N‐bromo amide (2 steps)• 2.  conversion of the N‐bromo amide to an 

isocyanate (2 steps)• 3.  hydrolysis of the isocyanate (2 steps)

RCNH2

O

RCNHBr

O

RNCO RNH2

Step 1

O•• ••

– ••H

••

RC

O

N

••

•• H

H

Step 1

O•• ••

– ••H

H

O••••

H

••

RC

O

N

••

•• H

H

RC

O

N

••

••

–

H

••••

Step 2

••••

••Br Br•• ••

••

RC

O

N

••

••

–

H

••••

Step 2

••••

••

••

RC

O

N

••

•• Br

H••••

••Br Br•• ••

••Br•••• ••••

–

RC

O

N

••

••

–

H

••••

Step 3

••

RC

O

N

••

•• ••••

••Br

H

O•• ••

– ••H

Step 3

••

RC

O

N

••

•• ••••

••Br

H

O•• ••

– ••H

••

H

O•• H

C

O

N

••

••

–••••

••••

••Br

R

Step 4

••

C

O

N

••

••R

Br•••• ••••

–

C

O

N

••–

••

••

••••

••Br

R

••

Steps 5 and 6

••

C

O

N

••

••R

H2O

HO–

••

C

O

N

••

••R

O

H

••••••

–

+ CO32–NH2R

••

Mechanism of Diazonium salt formation

H O N O + H +

H 2 O

+

nitrosoniumion

R NH 2

N O++

R NH

H

N O+

N-nitrosoammoniumion

R NH

H

N O+

+ H 2 O R N

H

N O + H 3 O +

N-nitrosamine

R N

H

N Otautomerization

R N N OH

a diazenol

R N N OH + H + R N N OH

H

R N N OH

HR N N + H 2 O

+

a diazoniumion

N OOH

H

+

N OOH

H

+

+

+

N O+

Basicity of amines

The greater the availability of the lone pair electrons on nitrogen, the greater the base.

Kb = [RNH3+] [OH-] / RNH2

In the old days, pKb was a measure of base strength.

pKb = - log Kb

The stronger the base the lower the pKb

EFFECTS ON AMINE BASICITY

1. INDUCTIVE EFFECT - ALKYL SUBSTITUTION

METHYL GROUP INCREASES ELECTRON DENSITY ON N

3.36 3.28 2 METHYLS ARE BETTER THAN ONE

WATCH OUT THREE METHYL GROUPS DECREASES BASICITY pKb = 4.26 - Steric inhibition of solvation of HOH with the NH+ of the R3NH+ cation.

The greater the availability of the lone pair electrons on nitrogen, the greater the base.

Kb = [RNH3+] [OH-] / RNH2

In the old days, pKb was a measure of base strength.

pKb = - log Kb

The stronger the base the lower the pKb

EFFECTS ON AMINE BASICITY

1. INDUCTIVE EFFECT - ALKYL SUBSTITUTION

METHYL GROUP INCREASES ELECTRON DENSITY ON N

3.36 3.28 2 METHYLS ARE BETTER THAN ONE

WATCH OUT THREE METHYL GROUPS DECREASES BASICITY pKb = 4.26 - Steric inhibition of solvation of HOH with the NH+ of the R3NH+ cation.

Reimer‐Tiemann Reaction Mechanism

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