Synthesis, single-crystal exploration, hirshfeld surface analysis, and DFT investigation of the thiosemicarbazones

Abstract

Thiosemicarbazones (TSCs) are considered as one of the most significant classes of organic compounds in recent time due to their applications in pharmaceutical chemistry. Two TSCs, (E)-4-((2-(cyclohexyl-carbamothioyl)hydrazineylidene)methyl)benzoic acid (CHMB) and (E)-2-(4-ethoxy-2-hydroxy-benzylidene)-N-(3-methoxyphenyl)-hydrazine-1-carbothioamide (BMHC), were successfully prepared via condensation reaction using substituted hydrazinecarbothioamide and substituted benzaldehydes. The detailed crystallographic investigation showed that the O-H···O and N-H···S bonding in CHMB and the N-H···O, O-H···S, and C-H···S bonding in BMHC, respectively, are responsible for the crystal packing. The Hirshfeld surface study showed the crystal packing of both compounds to be stabilized by non-covalent interactions. The density functional theory (DFT) study showed that the optimized geometries are close to the experimental structures while the frontier molecular orbital (FMO) analysis implied that CHMB is more reactive in redox reactions. The charge analysis supports the formation of intra- and intermolecular hydrogen bonds whereas the Natural Bonding Orbitals (NBO) analysis implies that both compounds possess noticeable stability, with somewhat higher stability of BMHC. CHMB should be considered as more stable in oxidation reactions than BMHC but should be much more prone to the reduction reactions. The Molecular Electrostatic Potential (MEP) analysis implies noticeable reactivity of both compounds along with formation of the intermolecular hydrogen bonding.