Experimental strategies for increasing the catalyst turnover number in a continuous Heck coupling reaction

This work presents a continuous Heck coupling reaction combined with organic solvent nanofiltration (OSN) separation of the catalyst in situ, using polymeric membranes at high temperature (80 C) and high concentration of base (>0.9 mol L-1). Two reactor configurations are investigated: a continuous single stirred tank reactor/membrane separator (m-CSTR) and a plug flow reactor (PFR) followed by m-CSTR (PFR-m-CSTR). The combined PFR-m-CSTR configuration was found to be the most promising, achieving conversions above 98% and high catalyst turnover numbers (TONs) of ∼20,000. In addition, low contamination of the product stream (∼27 mg Pd per kg of product) makes this process configuration attractive for the pharmaceutical industry.