Synthesis of tetrasubstituted thiophenes on solid-support using the Gewald reaction

The Gewald reaction was performed on solid support. This reaction combines a ketone or aldehyde, an activated nitrile, and sulfur in the presence of a suitable amine base to make tri- and tetrasubstituted thiophenes. After optimizing conditions for maximum yield and purity, the scope of the reaction was investigated. Finally, this method is highlighted in the synthesis of two biologically relevant compounds.