Toward the synthesis of thiadiazole-based therapeutic agents: synthesis, spectroscopic study, X-ray analysis, and cross-coupling reactions of the key intermediate 3,5-diiodo-1,2,4-thiadiazole

Abstract

The 1,2,4-thiadiazole moiety is an important component of several biologically active compounds, and varying substituents on this aromatic ring is one of the possible methods to develop novel thiadiazole-based drugs for medicine. A key building block to this end, namely 3,5-diiodo-1,2,4-thiadiazole (1), has been synthesized and characterized in this work for the first time. 1 has exhibited high selectivity for the replacement of iodine atom at position C5 (carbon next to sulfur) in Sonogashira-type cross-coupling reactions with phenylacetylene. Therefore, 3-iodo-5-(phenylethynyl)-1,2,4-thiadiazole (4) or 3,5-bis(phenylethynyl)-1,2,4-thiadiazole (5) could be synthesized selectively depending on reaction conditions. All three novel molecules have been characterized by NMR, IR, Raman, mass, and UV spectroscopies, and their solid phase structures have been determined by single-crystal X-ray diffraction. 1 is expected to be a key starting material for producing thiadiazole-based therapeutic agents using cross-coupling reactions.