Batch versus continuous mg-scale synthesis of chalcone epoxide with soluble polyethylene glycol poly- l-leucine catalyst

Abstract

The polyethylene glycol poly- l-leucine catalysed asymmetric epoxidation of chalcone was carried out in a laboratory batch reactor. At initial concentrations of poly- l-leucine, chalcone, peroxide and 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) of 13.47 g/l, 0.0802 mol/l, 0.132 mol/l and 0.22 mol/l, respectively, the conversion was 94.9% and enantioselectivity was 90.3%. The peroxide deprotonation time by DBU and sequence of reactant addition were found to affect the reaction outcome. Based on these results, a suitable protocol for continuous runs was established. These were carried out in a setup comprising two micromixers and two tubular microreactors the first for deprotonation and the second for epoxidation. Slow mixing of the poly- l-leucine catalyst due to its low molecular diffusivity was identified as a potential cause for the worse performance of the continuous system compared to the batch reactor. This however was rectified when peroxide and poly- l-leucine were pre-mixed prior to entering the continuous reactor system.