Synthesis, X-Ray Structural Analysis and Computational Studies of a Novel Bis(2-Thienyl)Disulfide Derivative

Abstract

The reaction of ethyl 3-oxobutanoate, carbon disulfide, and chloroacetone in the presence of K2CO3 afforded a novel bis(2-thienyl)disulfide derivative (4). The structure of the synthesized compound was confirmed by spectral and X-ray analyses. Hirshfeld quantitative analysis of molecular packing showed that the H···H (40.8–42.1%), O···H (19.7–23.9%), S···H (11.1–13.8%), and C···H (11.9–12.1%) contacts were the most common intermolecular interactions in the crystal. Density functional theory (DFT) calculations were used to perform the charge population analysis and simulate the experimental NMR chemical shifts. Compound 4 was also evaluated in silico against dihydrofolate reductase to elucidate the binding mechanism and orientation around the active sites.