Delépine reaction

The Delépine reaction is the organic synthesis of primary amines (4) by reaction of benzyl or alkyl halides (1) with hexamethylenetetramine (2) followed by acid hydrolysis of the quaternary ammonium salt (3).

[1][2] It is named after the French chemist Stéphane Marcel Delépine (1871–1965).

Downsides include that the reaction is often performed using chloroform as solvent, which is toxic, and poor atom economy, including the formation of several equivalents of formaldehyde (a known carcinogen) during quaternary ammonium salt formation.

By refluxing in concentrated ethanolic hydrochloric acid solution this salt is converted to the primary amine together with formaldehyde (as the acetal with ethanol) and ammonium chloride.

Depending on the hydrolysis conditions and structure, the nitrogen might instead be lost from the carbon where it had bonded in the first step to give a benzylic aldehyde (the Sommelet reaction).