An efficient heterogeneous catalyst (CuO@ARF) for on-water C-S coupling reaction: an application to the synthesis of phenothiazine structural scaffold

Abstract

Background: Aryl sulfides have significant importance from biological and pharmaceutical aspects. Transition metal-catalyzed carbon-sulfur cross-coupling reaction represents an important tool for the synthesis of sulfides. Among various transition metals, copper salts or oxides have found vast applicability. Results: A simple procedure for the preparation of poly-ionic amberlite resins embedded with copper oxide nanoparticles (CuO NPs) (denoted as CuO@ARF) has been developed, characterized, and employed for the first time as a heterogeneous ligand-free catalyst for 'on-water' C-S cross-coupling reaction. The NPs of CuO with an average size (approximately 2.6 nm), as determined from high resolution transmission electron microscopy (HRTEM) images, are found to be a potentially active, chemoselective, and recyclable catalyst for the preparation of symmetrical and unsymmetrical aryl sulfides. Recycling of the catalyst was performed successfully for five consecutive runs, and apparently no leaching was observed in a hot filtration test. Excellent chemoselectivity between iodo- and bromo-arene has been exploited in step-wise C-S and C-N couplings to synthesize bioactive heterocyclic scaffold phenothiazine. Conclusions: An efficient method is established for the C-S cross-coupling reaction using heterogeneous catalyst CuO@ARF under ligand-free on-water condition. The catalyst is highly chemoselective among different aryl halides, which has been demonstrated in the synthesis heterocyclic scaffold phenothiazine. Furthermore, it is recyclable for five consecutive runs examined.