Catalyst-Free Oxidative Coupling of Amines to Imines in Microdroplets

Imines are valuable intermediates and building blocks in fine chemicals and pharmaceutical synthesis. Oxidative coupling of amines represents an attractive route to imine formation. However, conventional methods rely on metal catalysts, external oxidants, or thermal and photochemical activation, involving multistep processes, harsh conditions, and environmental concerns. Here, we report that amines undergo oxidative coupling to imines within aqueous microdroplets at room temperature, without any catalyst or oxidant. The molecular structures of products were confirmed by mass spectrometry, UV–vis spectroscopy, and 1 H NMR analysis. Substrate scope studies revealed that the microdroplet system enables both self-coupling and cross-coupling of amines, highlighting its broad generality. Radical trapping experiments and density functional theory calculations suggest reactive oxygen species, including hydroxyl radicals and hydrogen peroxide, are likely involved in the oxidative process occurring at the microdroplet interface. This work introduces a simple, rapid, and environmentally benign strategy for imine synthesis and underscores the unique potential of microdroplet chemistry in advancing green oxidative coupling reactions.