Novel annulated thiophene derivatives: Synthesis, spectroscopic, X-ray, Hirshfeld surface analysis, DFT, biological, cytotoxic and molecular docking studies

Abstract

Ethyl-2-amino-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxylate (1) as a precursor derivative was used for the synthesis of variable heterocyclic compounds through its reactions with different reagents such as 9-anthraldehyde, 4-acetylbiphenyl, ethyl chloroacetate, ethyl benzoylacetate, chloroacetonitrile and diethyl malonate. Both conventional thermal and microwave irradiation techniques were used in the synthetic procedures. Molecular formulae and structures of the obtained derivatives were elucidated using different analytical and spectroscopic tools such as IR, 1H-, 13C-NMR as well as mass spectrometry. Variable structure features were observed for the products. The structure and crystal surface analysis of 1 were also obtained from the X-ray diffraction and Hirshfeld studies. Energy optimized structures of the reported compounds were performed by density functional theory (DFT/B3LYP) with the basis set 6-31 G and double zeta plus polarization (d,p). Quantum reactivity descriptors were calculated and correlated with their biological properties. The reported derivatives were analyzed for antimicrobial and cytotoxic inhibitions. The molecular docking studies of compounds were investigated as well. Structure and activity relationship of the reported compounds were correlated with the data of antimicrobial and cytotoxicity activity.