On a simple hydrogen cyanide-based access to piperazin-2-ones

This report describes a scope exploration of a rarely used access to piperazin-2-ones from carbonyls, hydrogen cyanide (generated in situ from acetic acid and potassium cyanide) and ethylenediamine as well as N-or C-substituted alkyl 1,2-diamines. Our findings show that this synthesis plausibly proceeds via imines and/or imidazoline intermediates and, upon addition of hydrogen cyanide, to α,δ-diaminonitriles.Their ensuing cyclisation leads to piperazin-2-imines which then require a hydrolysis stage at high temperature, using a microwave oven, to generate the corresponding piperazin-2-ones. Although the reaction proceeds sometimes in very modest yields (ranging from 4 to 84%), its rather large scope (illustrated by 73 original examples) are described here-as well as the many commercially available starting material offer at least a one-pot alternative to prepare original libraries of chemicals featuring a piperazin-2-one component.

Publication History

Received: 25 July 2025

Accepted after revision: 29 August 2025

Accepted Manuscript online:
19 September 2025