Dualism of 1,2,4-oxadiazole ring in noncovalent interactions with carboxylic group

A number of cyclohexane and cyclohexene carboxylic acids bearing 1,2,4-oxadiazole substituent were prepared via condensation of amidoximes with anhydrides of corresponding dicarboxylic acids. All prepared compounds were studied via HRMS, 1 H and 13 C NMR. In addition, for five acids crystalline structures were obtained via X-ray diffraction analysis. Inspection of these X-ray structures revealed two type previously undescribed noncovalent interactions between oxadiazole ring and carboxylic group: O(carboxyl) center dot center dot center dot C(oxadiazole) and O(oxadiazole) center dot center dot center dot C(carboxyl). Computational investigation by a number of theoretical approaches (the quantum theory of atoms in molecules, the independent gradient model, natural bond orbital, molecular electrostatic potential, and Kohn-Sham energy decomposition analyses, as well as the domain based local pair-natural orbital coupled-cluster and atomic-dipole-moment-corrected Hirshfeld methods) demonstrated that these interactions are caused by the packing effect and have an electrostatic and dispersive nature. (c) 2022 Elsevier B.V. All rights reserved.

Automated summary

A series of cyclohexane and cyclohexene carboxylic acids bearing 1,2,4-oxadiazole substituent were prepared via condensation reactions. The compounds were characterized by HRMS, 1 H and 13 C NMR, and the crystal structures of five acids were determined using X-ray diffraction analysis. Computational investigations revealed previously undescribed noncovalent interactions between the oxadiazole ring and carboxylic group, which were found to be caused by packing effects and have electrostatic and dispersive nature.