From Lab Scale to Kilolab Scale using a Multimode Batch Microwave Reactor

Abstract

An evaluation of a new bench-top microwave batch reactor that uses a single 1 L reaction vessel is presented. Several microwave-assisted organic reactions have been scaled-up, including Newman Kwart and Diels-Alder reactions, Pd-catalyzed cross-couplings, heterocycle synthesis, aromatic substitution and a Knoevenagel condensation. A range of different solvents (high and low microwave absorbing), varying reaction times (4 s up to 2 h) and temperatures (120 °C to 250 °C) have been explored in these investigations. For all studied transformations it was possible to perform a direct scale-up (up to 720 mL applied volume) without changing the previously optimized reaction conditions achieved in a laboratory scale single-mode microwave instrument (2-20 mL processing volume), obtaining similar isolated product yields. A scalability up to 360 fold, when moving from 3 mmol up to 1.08 mol, was demonstrated and isolated product yields up to 300 g (2.5 mol scale) in a single run could be accomplished, providing the potential for a kilogram output per day by performing multiple sequential runs