Synthesis of Enaminothiones and Computational Investigation of Intramolecular Hydrogen Bonding Strength and Substituent Effects Using DFT, QTAIM, and NCI.

Abstract

Enaminothiones were prepared, and the effects of aromatic and aliphatic substitutions on the strength of intramolecular hydrogen bonds were studied via DFT calculations (ωB97XD/6‐311++G(d,p)), QTAIM and NCI analyses. The results showed that aromatic substitutions enhance the strength of hydrogen bonds, as they result in shorter S…N distances, higher electron density (ρBCP), and stronger hydrogen bond energy (35.80–36.69 kJ/mol) than those of aliphatic compounds. NMR measurements confirmed this with greater chemical shifts of the NH proton in aromatic compounds (15.74–15.88 ppm), and NCI analysis revealed more negative sign(λ2)ρ values, indicating stronger bonding. This study confirms the role of substitutions in modifying the strength of hydrogen bonds, which may have an impact on the design of pharmaceutical compounds and chemically active materials.