1. The Hofmann
Rearrangement
Dr. Khalid Hussain

2. Introduction
 In previous lectures we have discussed the
movement of alkyl or aryl groups etc. that
involves the migration to carbon atom, either
cation or electron deficient (carbene).
 Like carbon, nitrogen can easily be made
electron deficient, R2N** or RN **
* **
 Hence, it is expected to facilitate migration to
itself as it is observed in R3C+ of R2C**

3. Example is Hofmann
rearrangement
Conversion of an amide to an amine
containing 1 carbon less by the action of
alkaline hypobromite (BrO-)
O
BrO-
RCNH2 RNH2 + CO2

4. The Hofmann Rearrangement
Treatment of amides with bromine in basic solution
gives an amine with loss of the carbonyl carbon in
the form of carbon dioxide.
O
Br2/NaOH
RCNH2 RNH2 + CO2

5. The Hofmann Rearrangement
Amides on reacting with bromine and sodium
hydroxide form isocyanate which upon
hydrolysis and decarboxylation produce
amine

6. Examples
O
Br2, NaOH
(CH3)3CCH2CNH2 (CH3)3CCH2NH2
H2O
3,3 dimethyl butylamide 2,2 dimethyl propylamine
O
Br2, KOH
CNH2 NH2
H2O
Br Br

7. Mechanism of rearrangement
1- Removal of proton from nitrogen of the amide
2- Formation of N-bromo amide
3- Removal of another proton from nitrogen
4- migration of alkyl group
5- Formation of isocynate
6-Hydrolysis of isocyanate

8. Mechanism of rearrangement
R C NH2 R C NH-Br
O O
Br2/NaOH OH-
Isocyanate R C N-Br
C N R +
O O
**
R C N
**
Br-
H2O O
-
C N R
O **
R-NH-COOH +
Carbamic acid
CO2 + R-NH2

9. Curtius, degradation of acid azides, and Lossen,
decomposition of hydroximic acid, also involves
Hofmann type rearrangement
O O O
NH2-OH NH2-NH2 hydrazide
R-C-NH-OH R-C-O-Et R-C-NH-NH2
OH- NaNO2 HCl
O O O
-OH- ** Heat +
**
R-C-N-OH R-C-N R-C-N-N N
**
-N2 **
Acyl azide
O==C==N--R
Hydroxamic acid isocyanate

10. Br2
OH-
OH-
-Br