Waste minimized synthesis of pharmaceutically active compounds via heterogeneous manganese catalysed C–H oxidation in flow

Abstract

Herein, we present our results on the development of a continuous flow protocol enabling the waste minimised synthesis of relevant pharmaceuticals and natural compounds. Heterogeneous manganese catalytic systems have been used in combination with molecular oxygen to promote the C–H oxidative coupling of 2-aminophenols, benzenetriols and o-phenylenediamines to access a variety of 2-aminophenoxazin-3-ones (2a–i) and related diaminophenazines (2j–k) and purpurogallin (2l) with minimal metal contamination. Making use of safe and green cyclopentyl methyl ether (CPME), this methodology allowed a fast synthesis of fully decorated molecular entities, preserving the stability of the heterogeneous catalyst which showed minimal metal leaching, with minimal waste production (low E-factor).