Divergent synthesis of polysubstituted 2H-imidazoles and 3-imidazolines from α-aminoketones, ketones, and ammonium acetate.

Abstract

A divergent multicomponent reaction of α-aminoketone, ketones and ammonium acetate has been developed for the selective synthesis of 2H-imidazoles and 3-imidazolines. Under mild, non-oxidative conditions, the reaction delivers 3-imidazolines, while aerobic oxidation enables further dehydrogenation to furnish aromatic 2H-imidazoles. This protocol features broad substrate compatibility, tolerating diverse aliphatic, heteroatom-containing and drug-derived ketone substrates. Gram-scale and post-modification experiments demonstrate the practicability of the method. Mechanistic investigations reveal that 3-imidazoline acts as a key intermediate toward 2H-imidazole, and ammonium acetate serves as both ammonia source and mild acid promoter. This divergent strategy offers a convenient route to access two important nitrogen heterocycles from identical starting materials.