C-O bond Formation in a Microfluidic Reactor: High Yield SNAr Substitution of Heteroaryl Chlorides

Tetrahedron Lett. 2016 May 11;57(19):2059-2062. doi: 10.1016/j.tetlet.2016.03.095.

Abstract

This study describes our development of a novel and efficient procedure for C-O bond formation under mild conditions, for coupling heteroaryl chlorides with phenols or primary aliphatic alcohols. We utilized a continuous-flow microfluidic reactor for C-O bond formation in electron-deficient pyrimidines and pyridines in a much more facile manner with a cleaner reaction profile, high yield, quick scalability and without the need for the transition metal catalyst. This approach can be of general utility to make C-O bond containing intermediates of industrial importance in a continuous and safe manner.

Keywords: C–O bond; Flow chemistry; Micro-fluidic reactor; SNAr reaction.