Solid-phase synthesis of a potent cytotoxic Pd(II) pincer complex featuring quinoxaline and thiocarbamate coordination arms

Abstract

A new representative of hybrid pincer ligands has been synthesized by the thiocarbamoylation of a potassium salt of 3-(quinoxalin-2-yl)phenol with ClC(S)NMe₂ to probe its cyclopalladation features in solution and under solvent-free conditions. The compound obtained is shown to readily undergo cyclometalation under the action of PdCl₂(NCPh)₂ upon heating in benzonitrile and, more importantly, in the absence of an added solvent, using the preliminary ground mixture of reactants as the starting material, which provides a powerful and green alternative to the conventional solution-based synthesis. The course and outcome of the solid-phase reaction were analyzed by IR spectroscopy, elemental and SEM/EDS analysis. The possibility to scale up the solid-phase synthesis using a simple thermoreactor was demonstrated for the first time. The resulting palladacycle exhibited high cytotoxic activity against several solid and hematopoietic cancer cell lines.