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
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
