Membrane separation between homogeneous palladium-based catalysts and industrial active pharmaceutical ingredients from a complex organic solvent matrix: First approach using ceramic membranes

Palladium-based homogeneous catalysts are indispensable in the pharmaceutical field due to the high reaction yields and high selectivity they can reach. However, they are toxic and sensitive to oxidation. Isolating these complexes from pharmaceutical molecules at the end of the synthesis without degrading both compounds could therefore lead to major environmental and economic gains. This study focuses on the separation between a real pharmaceutical intermediate at around 600 g/mol and a palladium catalyst PdCl 2 (PPh 3 ) 2 at 701.9 g/mol using ceramic membranes in organic solvent phase. For improving this separation, substitute catalysts with higher molecular weights and/or higher steric hindrances had been selected, and MWCO of 1000, 750, and 250 Da had been evaluated. The interest of catalyst enlargement had been confirmed with Pd retentions from 13 % (reference) to 18 % (heavier complex), but this approach was limited by economic aspect which restricted the choice of potential substitutes. Nanofiltration membranes with lower cut-off points have led to slightly higher retentions, but membrane characterization concluded that experimental MWCO were similar between all membranes, therefore raising questions about the definition of MWCO for different manufacturers.