Hofmann rearrangement

Hofmann Rearrangement Definition:


When amides are treated with halide and base, a rearrangement occurs, resulting in the loss of carbon dioxide and the formation of an amine.



Hofmann rearrangement Explained:


The Hofmann rearrangement is a special halogenation reaction in which primary amides in the presence of the base are transformed in primary amines by expelling the carbonyl group from molecules.

In this treatment, primary and secondary amides are deprotonated at nitrogen giving amidate ions which are synthetically useful nucleophiles.

And this is the first step of the mechanism. Hydroxide removes the hydrogen from hydrogen. These both hydrogens on the nitrogen next to the carbonyl group are acidic and are readily deprotonated by a base. The nitrogen-hydrogen bond breaks and the amidate ion which is formed is stabilized by resonance.



In the second step, by reforming of the carbonyl group the carbon-nitrogen double bond breaks and these electrons attack the bromine atom which expels the other one.



In the third step, the second proton on the nitrogen is abstracted by the additional base to give an N-bromoamidate. This ion is also resonance stabilized.



The fourth step is Hofmann rearrangement. The ion formed in the previous step contains a weak nitrogen-bromide bond and a good potential leaving group. When carbonyl group is reformed, the loss of the leaving group (bromide ion) followed by the migration of the alkyl (R) group from the carbonyl carbon to nitrogen. The product of this rearrangement is an isocyanate.



And in the last step, hydroxide attacks carbon atom of isocyanate because this carbon is located between two electronegative elements (oxygen and nitrogen) and has a strong positive charge. By this hydrolize, an unstable carbamic acid is formed which decompose to carbon dioxide and the amine.