Hofmann rearrangement

In the Hofmann rearrangement (also Hofmann degradation or Hofmann amide degradation) is a name reaction in organic chemistry, which was named after its discoverer, August Wilhelm von Hofmann. Here is an unsubstituted carboxamide with bromine Br2 is reacted in the presence of a base in water. The result is a to the carbonyl group shortened amine. This elimination of the carbonyl group of the amide is closely related to the Curtius reaction, the Lossen rearrangement, and the Schmidt reaction.

Overview reaction

The Hofmann rearrangement is a degradation of carboxylic acid amides to primary amines.

Mechanism

In the first step, the hydroxide engages a proton of the amino group. In the next step, a positively polarized bromine to the negatively charged nitrogen binds. These two reaction steps can be summarized in one: In an alkaline medium is formed from the reactive bromine hypobromite, which engages with its partial positive charge, the nucleophilic amino group, it creates a N- bromo amide. This can be deprotonated by another hydroxide ion because of its NH- acidity. Of this anion, the bromide is split off and R ( alkyl or aryl group) of the nitrene migrates under formation of an isocyanate to the nitrogen. The isocyanate outsourced to water and reacts to a carbamic acid. It is not stable in aqueous alkaline solution and decarboxylated. This produces a primary amine.

For related reactions, such as the Curtius rearrangement, the Schmidt reaction or the Lossen rearrangement, the intermediate nitrene can be found in the corresponding reaction step does not actually formulate as an intermediate. Rather, in a concerted reaction via a rearrangement forms the isocyanate directly from the N- bromo amide.

Variants

Bromine may be replaced with 1,8- diazabicyclo [5.4.0] undec -7-ene (DBU) as a base by means of other reagents, such as chlorine (Cl2) or N-bromosuccinimide (NBS). In the following example, the intermediate isocyanate is reacted with methanol to form a urethane:

As an alternative to bromine may be ( bis ( trifluoroacetoxy ) iodo ) benzene also used.