Mechanistic Studies on the Michael Addition of Amines and Hydrazines To Nitrostyrenes: Nitroalkane Elimination via a Retro-aza-Henry-Type Process

J Org Chem. 2018 Feb 2;83(3):1176-1184. doi: 10.1021/acs.joc.7b02637. Epub 2018 Jan 11.


In this article we report on the mechanistic studies of the Michael addition of amines and hydrazines to nitrostyrenes. Under the present conditions, the corresponding N-alkyl/aryl substituted benzyl imines and N-methyl/phenyl substituted benzyl hydrazones were observed via a retro-aza-Henry-type process. By combining organic synthesis and characterization experiments with computational chemistry calculations, we reveal that this reaction proceeds via a protic solvent-mediated mechanism. Experiments in deuterated methanol CD3OD reveal the synthesis and isolation of the corresponding deuterated intermediated Michael adduct, results that support the proposed slovent-mediated pathway. From the synthetic point of view, the reaction occurs under mild, noncatalytic conditions and can be used as a useful platform to yield the biologically important N-methyl pyrazoles in a one-pot manner, simple starting with the corresponding nitrostyrenes and the methylhydrazine.

Publication types

  • Research Support, Non-U.S. Gov't