Chemical Sciences: A Manual for CSIR-UGC National Eligibility Test for Lectureship and JRF/Named Reactions/Hofmann Rearrangement

The Hofmann rearrangement is the organic reaction of a primary amide to a primary amine with one fewer carbon atom.


 * [[Image:Hofmann Rearrangement Scheme.png|400px|The Hofmann rearrangment]]

The reaction is named after its discoverer: August Wilhelm von Hofmann. This reaction is also sometimes called the Hofmann degradation, and should not be confused with the Hofmann  elimination.

Mechanism
The reaction of bromine with sodium hydroxide forms sodium hypobromite in situ, which transforms the primary amide into an intermediate isocyanate. The intermediate isocyanate is hydrolyzed to a primary amine giving off carbon dioxide.


 * [[Image:Hoffmann_rearrangement_mechanism.svg|400px]]

Variations
Several reagents can substitute for bromine. N-Bromosuccinimide and 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) can effect a Hofmann rearrangement. In the following example, the intermediate isocyanate is trapped by methanol forming a carbamate.
 * [[Image:Hoffmann_Rearrangement_NBS.png|400px|The Hofmann rearrangement using NBS]]

In a similar fashion the intermediate isocyanate can be trapped by tert-butanol yielding the t-butoxycarbonyl (Boc)-protected amine.

A mild alternative to bromine is also (bis(trifluoroacetoxy)iodo)benzene.