Proton tautomerism and stereoisomerism of 4-amino-1,3-thiazol-2(5H)-one derivatives bearing substituents with opposite electronic effects: Synthesis, structure and spectroscopic studies

New compounds of high pharmacological interest: 5-dimethylaminomethylidene-4-phenylamino-1,3-thiazol-2(5H)-one and 5-methoxycarbonylmethylidene-4-phenylamino-1,3-thiazol-2(5H)-one, were syn-thesized and investigated. Their crystal structure, chemical environment, and intermolecular interactions were studied by X-ray diffraction method and by NMR and FT-IR spectroscopy. The molecular interac-tions in the crystals were analyzed using Density Functional Theory (DFT), Quantum Theory of Atoms in Molecules (QTAIM), Hirshfeld surfaces, and fingerprint plots, with special emphasis on stereoisomerism and proton tautomerism. Both investigated compounds occur in the solution (DMSO) and in the solid state in the amine tautomeric form. The ylidene substituent with electron-donating effect only could sig-nificantly decrease the resonance effect of the carbonylimino group with the phenylamino moiety. In the molecules of both compounds, the phenylamino group has a synperiplanar conformation, and the yli-dene substituent has the Z configuration. The theoretical conformational analysis shows that the coplanar arrangement of the thiazolin-2-one and phenyl systems is preferred.(c) 2022 Published by Elsevier B.V.

Automated summary

New compounds, 5-dimethylaminomethylidene-4-phenylamino-1,3-thiazol-2(5H)-one and 5-methoxycarbonylmethylidene-4-phenylamino-1,3-thiazol-2(5H)-one, were synthesized and studied. Their crystal structure, chemical environment, and intermolecular interactions were analyzed using various methods, including X-ray diffraction, NMR, and FT-IR spectroscopy. The compounds exhibited amine tautomeric form in both solution and solid state, and the molecular interactions were investigated with a focus on stereoisomerism and proton tautomerism. The conformational analysis revealed the preferred coplanar arrangement of the thiazolin-2-one and phenyl systems.