Synthesis, X-ray crystal structure, Hirshfeld analysis and computational investigation of bis(methylthio)acrylonitrile with antimicrobial and docking evaluation

Abstract

In this investigation, we studied the reactivity of 3-oxopropanenitrile derivatives 3 with CS2 in the presence of sodium hydride to give the acrylonitrile potassium salt intermediate 4 which the easily reacted with methyl iodide to afford the corresponding 2-(3-methylbenzofuran-2-carbonyl)-3,3-bis(methylthio)acrylonitrile (5). The reactants were optimized utilized B3LYP/6-311(G) to elucidate their physical descriptors of them and confirm the stability of compound 5 and its reactivity due to presence of different reactive sites using FMO, ESP and MEP. Moreover, the crystal structure of bis(methylthio)acrylonitrile derivative 5 showed a triclinic structure and P-1 space group, also Hirshfeld analysis of 5 reveled contacts (H….H) with (43.1%), H….C/H….N/H…O/H….S with contributed 4.8%, 5.2, 3.5 and 4.0%, respectively. It also showed higher intramolecular interaction in its molecular packing of strong acceptor-donor interaction in C4—H4A···N1i with distance of 3.423Å and angle = 134.58o. The comparative study between experimental and theoretical results according to its bond length, bond angles, 1HNMR and 13CNMR were in strong correlation with DFT/B3LYP/6-311(G) basis set. Moreover, compound 5 exhibited higher antimicrobial activities when compared with different standard drugs which was confirmed via molecular docking with different types of proteins.