In the presence of an aqueous base and a halogen, primary amides can lose the carbonyl (as carbon dioxide) and undergo rearrangement to form primary amines. This reaction, called the Hofmann rearrangement, can produce primary amines (aryl and alkyl) in high yields without contamination by secondary and tertiary amines.

In the Curtius rearrangement, acyl azides are converted into primary amines under thermal conditions, accompanied by the loss of gaseous N₂ and CO₂. The loss of nitrogen acts as a driving force to complete the reaction.

The Hofmann and Curtius rearrangement reactions are applied in the synthesis of phentermine (an appetite-suppressant drug) and tranylcypromine (an antidepressant drug), respectively.

If the substrates are optically active, both rearrangement reactions occur with retention of configuration.