High Efficiency Microwave Flow Chemistry Towards Synthesis of Functional Materials and Pharmaceutical Cores

Abstract

Microwave (MW) heating benefits organic synthesis by affording higher product yields in shorter time periods than conventional heating, yet it suffers from poor scalability and is limited to polar solvents in typical batch mode reactors. Herein, we report a microwave flow reactor using a solid-state semiconductor MW generator. The tunable, single-mode MW heating allows high efficiency, scalable organic synthesis, rapid reaction optimization and is applicable to non-polar solvents (o-Xylene and CPME can be rapidly heated to ca. 260 oC). Auto-frequency tuning compensates for changes in the microwave absorption properties (permittivity, epsilon) with increasing temperature, affording excellent temperature and process control. This technology unlocked unprecedented g/h productivity of C60/fullerene-indene monoadduct (IC60MA) and facilitated a novel, transition metal-free amide-styrene coupling reaction for synthesis of amide-containing pharmaceutical cores in up to 65 g/h (Figure 1). An ortho-Claisen rearrangement reaction was rapidly optimised.