Study of the intermolecular interactions in the crystal structure formation of two new 4,5-disubstituted vicinal triazoles

Abstract

Two new heterocycles, containing the vicinal triazole pharmacophore, were synthesized and studied exhaustively by spectroscopic methods, computational calculations and X-ray diffraction. The compounds (2‑hydroxy‑3,5-dimethylphenyl)[5-(trifluoromethyl)-2H-1,2,3-triazol-4-yl]methanone (a) and (5‑chloro‑2‑hydroxy‑3-methylphenyl)[5-(trifluoromethyl)-2H-1,2,3-triazol-4-yl]methanone (b) are interesting because their structure allows the nitrogen atoms of the pharmacophore to remain free, increasing its interaction potential. Furthermore, 4,5-disubstituted vicinal triazoles have received less attention since they cannot be produced using click chemistry.The crystal structure of both compounds was determined by X-ray diffraction methods. Quantum chemical calculations were implemented to support the analysis of vibrational and electronic spectroscopic properties by Density Functional Theory (DFT). The study of the intermolecular interactions was undertaken through Molecular Electrostatic Potential (MEP) maps, Hirshfeld surfaces (HS), Natural Bond Orbitals (NBO) and Quantum Theory of Atoms in Molecules (QTAIM). Strong (O-H···O and N-H···O) and weak (C-H···F and N-H···F) hydrogen bonding interactions together with F···F, O···C and π···π stacking contacts are the basis on which the sheets and layers of the studied compounds are formed. The dispersive energy component predominates in the stabilization of the layers. The intramolecular hydrogen bonding is much stronger in compound a, since the interaction is influenced by the intramolecular N-H···O contacts. The second-order stabilization energy (E(2), NBO) and the interaction energy (Eint, QTAIM) associated with this interaction support the analysis.