Green, fast and simple continuous-flow protocol for the N-alkylation of amines in a biphasic solvent system

Abstract

The alkylation of the nitrogen atom is a key reaction class for the synthesis of building blocks, APIs and other bioactive compounds. Herein, we report a green N-alkylation methodology that combines a simple continuous-flow protocol using readily accessible reagents and environmentally benign solvents, aiming to improve both efficiency and sustainability. This methodology enabled the synthesis of 15 derivatives, varying both the Michael acceptors and amine substrates, with yields of up to 93%. Transformation of selected APIs were also included to demonstrate the applicability of the process. Green-metric calculations were conducted to further highlight the sustainability potential of the methodology.