Hofmann Rearrangement PDF

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CHAPTER13 HofmannRearrangement BY, G.DEEPA

TheHofmannRearrangement

Treatment of amides with bromine in basic solution gives an amine with loss of the carbonyl carbon. O RCNH2

Br2 HO–

RNH2

+

CO32–

Examples O (CH3)3CCH2CNH2

Br2, NaOH

(CH3)3CCH2NH2

H2 O O

(94%)

Br2, KOH NH2

CNH2 H2 O Br

Br (87%)

MechanismoftheHofmannRearrangement

O RCNH2

O RCNHBr

RNCO

RNH2

•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)

Step1 ••

O •• – •• •O •

RC •N •

H

••

H

H

Step1 •• – • O• • •

•• • •

O •

H

RC •N •

H

H

•• •• O

H

H

Step2 •• – • O• • •

RC •N •

H

•• • Br • ••

••

Br •• ••

Step2 •• – • O• •

•• O ••

RC •N •

H

RC ••

Br •• ••

•• – • Br • • • ••

• •

H

••

Br •• ••

Step3 ••

O •• RC •N •

••

Br •• ••

H – •• •• O ••

H

Step3 •• – •O• • •

•• • •

R ••

Br •• ••

C •N •

••

Br •• ••

H – •• •• O ••

H

•• O ••

H

Step4 –

•• O ••

C R

•• • •O

R

N ••

r •• •• – • Br • • • ••

Steps5and6 •• •O •

•• O ••

H2 O

C R

C

N ••

R HO–

R

••

NH2

+

CO32–

N •• H

•• – O •• ••

MechanismofDiazonium saltformation H H

O

N

O

+

H

+

H

+

O

N

O

H +

+

O

N

H 2O

O

H

+

N

O

nitrosonium ion H +

R

NH

2

+

+

N

R

O

N

N

O

H N-nitrosoammonium ion H +

R

N

N

O

+

H 2O

R

N

N

+ H 3O

O

H N-nitrosamine

H

R

N

N

R

O

N

N

OH

tautomerization H

a diazenol

R

N

N

R

N

N

+

OH

+

H

+

+

R

N

H

O H

+

H R

O

N

N

N

H a diazonium ion

+

H 2O

+

Basicityofamines The greater the availability of the lone pair electrons on nitrogen, the greater the base. In the old days, pKb was a measure of base strength. Kb = [RNH3+] [OH-] / RNH2

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. In the old days, pKb was a measure of base strength. Kb = [RNH3+] [OH-] / RNH2

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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