Application of Thiol-Modified Dual-Pore Silica Beads as a Practical Scavenger of Leached Palladium Catalyst in C–C Coupling Reactions

A practical and efficient method for scavenging palladium leached into the reaction mixture using thiol-modified dual-pore silica beads has been developed. Reducing the level of metal contamination, especially palladium, in pharmaceutical and bioactive compounds and fine chemicals to below the regulatory value is quite important for the quality assurance of industrial products. We have evaluated the performance of dual-pore silica beads as a palladium scavenger by investigating their ability to eliminate the divalent palladium ions in dilute palladium(II) acetate in methanol (5 and 50 ppm) and ethyl acetate (5 ppm) solutions. The ability of the dual-pore silica beads to eliminate the palladium species leached from a 10% palladium on carbon (Pd/C) catalyst during the ligand- and copper-free 10% Pd/C-catalyzed Sonogashira-type coupling reaction was also investigated. The thiol-modified dual-pore silica beads exhibit a more rapid and effective elimination ability toward leached palladium species in the reaction mixture in comparison with commercially available conventional thiol-modified silica scavengers because of the effects of diffusion and perfusion due to the dual-pore skeleton of the silica beads. When methanol is used as a dilution and eluent solvent for the filtered reaction mixture, the leached palladium species were removed almost entirely (<1 ppm).