Sustainable purification-free synthesis of N–H ketimines by solid acid catalysis

Abstract

Abstract Among imines, nitrogen-unprotected ketimines ( N –H ketimines) are valuable precursors to nitrogen-containing compounds. However, their applications are limited compared with those of nitrogen-protected ketimines ( N –R ketimines) owing to difficulties in synthesis and purification. We develop remarkably simple methods for synthesizing and isolating high-purity N –H ketimines and N –H ketimine hydrochlorides via the dehydration–condensation of ketones with stoichiometric ammonia, generated in situ with inorganic solid acid catalysts. Our methods offer exceptionally broad substrate scope, use non-toxic and reusable catalysts, do not require tedious synthetic steps, are inexpensive, and are suited to large-scale production. Additionally, ketones can be easily converted to N –R ketimines, α-aminonitriles, and hydantoins in one pot via N –H ketimines. All products can be isolated by filtration or concentration; other purification methods, such as column chromatography, are not required. This study guides the advancement of the design of new transition metal catalysts and pharmaceutical synthesis.