Nitrogen Hofmann rearrangement

For the Hofmann rearrangement reaction, a carboxylic amide 1 is treated with hypobromite in aqueous alkaline solution. Initially an A-bromoamide 4 is formed. With two electron-withdrawing substituents at nitrogen the A-bromoamide shows NH-acidity, and can be deprotonated by hydroxide to give the anionic species 5. 

The conversion of an amide in this way is termed the Hofmann reaction or the Hofmann rearrangement. The mechanism of the reaction involves an intramolecular 1,2-carbon-to-nitrogen nucleophilic shift of the alkyl (or aryl) group... 

Generally, hypervalent iodine reagents are often better than traditional reagents of similar reactivity, with respect to efficiency and chemoselectivity - sometimes even stereoselectivity. Unusual reactivity is another interesting feature which has often resulted in unexpected transformation. Examples of such reactions may be found in the oxidation of nitrogen-containing compounds, the Hofmann rearrangement in acidic conditions, the acetalization of carbonyl compounds in alkali, the remote functionalization of steroids, etc. Some unique transformations were effected in the... 

The Hofmann rearrangement also involves a migration to an electron-deficient nitrogen. In this case, an amide is treated with Cl2 or Br2 in aqueous base, resulting in the formation of an amine with one less carbon. The original carbonyl carbon is lost as carbon dioxide. The mechanism is shown in Figure 22.7 and an example is provided by the following equation ... 

In the Hofmann rearrangement, a halide leaving group confers electrophilic character on the nitrogen atom. 

Hofmann rearrangement. Migration to electron-deficient nitrogen... 

Only amides of the type RCNH2 undergo the Hofmann rearrangement. The amide nitrogen must have two protons attached to it, of which one is replaced by bromine to give the A-bromo amide, whereas abstraction of the second by base is neces-... 

Gabriel synthesis, 875—876, 902 Hofmann rearrangement, 807-813, 822 reduction of nitrogen-containing... 

Amides are much less reactive than esters toward nucleophilic acyl substitution. They have greater resonance stabilization by the nitrogen lone pair, and they have a poorer leaving group (NH, in acid, and NH2 in base). Amides do show some special reactions the possibility of deprotonation of the nitrogen in 1° or 2C amides, reduction reactions that may form either amines or aldehydes, and a new process, the Hofmann rearrangement. 

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