New Isatin Based Thiosemicarbazone Derivatives: Synthesis, Spectroscopic Characterization and Theoretical Studies

Abstract

New isatin based thiosemicarbazone derivatives (1–7) were synthesized from various isatins and N-phenethylhydrazinecarbothioamide with good yields (61–93%). The thiosemicarbazide was prepared by the reaction of phenethyl isothiocyanate with hydrazine monohydrate. The structures and purity of all newly synthesized compounds were confirmed using standard spectroscopic methods, including 1H, 13C NMR, FT-IR, and elemental analysis. The electronic properties and conformations of the compounds were investigated by the DFT method and the agreement of the calculations with the experimental structural data was discussed comprehensively. The influence of various substituents on the compounds' electronic characteristics, thermodynamic stability, and potential reactivity was examined. The theoretical results revealed that the electronic properties are highly sensitive to the nature of the substituent on the isatin ring. Electron-donating groups were found to increase the HOMO–LUMO energy gap, thereby enhancing kinetic stability, while electron-withdrawing groups narrowed the energy gap, indicating increased chemical reactivity. Among the compounds, compound 7 bearing a nitro group was calculated to exhibit the highest reactivity and to be the most prone to nucleophilic attack. The structural and electronic properties of the synthesized isatin-based phenethyl thiosemicarbazones suggest strong potential for biological applications. Further in vitro and in vivo studies are clearly needed to evaluate their anticancer, enzyme inhibitory, and antimicrobial effects.

Keywords

• Thiosemicarbazones
• isatin
• schiff base
• spectroscopic techniques
• DFT calculations

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