Abstract

Flow Hydrogenations and Oxidations with Heterogeneous Catalysts

Joel Hawkins, Senior Research Fellow, Pfizer Global Research and Development

Flow hydrogenations and aerobic oxidations using heterogeneous catalysts in packed bed reactors will be described for the preparation of pharmaceutical intermediates. In the catalyst bed, the catalyst surface area is extremely high, and pressures and temperatures can be very high, promoting fast reactions by the brief, controlled exposure to these powerful reaction conditions. Rapid chemistry provides high throughput from small reactor volumes and short startup and shutdown times. The catalyst particle size is important, both for this high reactivity and for robust operation. Flowing solutions of organic substrates and gaseous reagents through beds of heterogeneous catalysts can greatly streamline processes if there are no byproducts, e.g. from hydrogen, or only innocuous byproducts, e.g. from oxygen giving water: the product streams can be directly flowed into the next synthetic step or concentrated to the product without added work up steps. In addition to streamlining processes, these reactions provide increased reactivity and/or selectivity relative to their batch reaction counterparts, and cases will be described with increased diastereoselectivity and increased chemoselectivity in flow hydrogenations. Lab and kilolab scale flow reactions will be described, with kinetic measurements relating these two scales.