Hofmann rearrangement

The Hofmann rearrangement is the organic reaction of a primary amide to a primary amine with one fewer carbon atom. The Hofmann rearrangement is the organic reaction of a primary amide to a primary amine with one fewer carbon atom. 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. The reaction of bromine with sodium hydroxide forms sodium hypobromite in situ, which transforms the primary amide into an intermediate isocyanate. The formation of an intermediate nitrene is not possible because it implies also the formation of a hydroxamic acid as a byproduct, which has never been observed. The intermediate isocyanate is hydrolyzed to a primary amine, giving off carbon dioxide. Several reagents can be substituted for bromine. Sodium hypochlorite, lead tetraacetate, N-bromosuccinimide, (bis(trifluoroacetoxy)iodo)benzene, and 1,8-diazabicycloundec-7-ene (DBU) can effect a Hofmann rearrangement. In the following example, the intermediate isocyanate is trapped by methanol, forming a carbamate. In a similar fashion, the intermediate isocyanate can be trapped by tert-butyl alcohol, yielding the tert-butoxycarbonyl (Boc)-protected amine. The Hofmann Rearrangement also can be used to yield carbamates from α,β-unsaturated or α-hydroxy amides or nitriles from α,β-acetylenic amides in good yields (≈70%). For amiloride, hypobromous acid was used to effect a Hofmann rearrangement.