Synthesis, X-ray characterization, Hirshfeld surface analysis and DFT calculations on tetrazolyl-phenol derivatives: H-bonds vs C-H•••π/π•••π interactions

Tetrazoles are nitrogen rich heterocycles with a broad spectrum of medicinal properties and potential for use as drugs. A significant number of FDA approved drugs incorporate the tetrazole moiety indicating the versatile pharmaceutical potential associated with this heteroaromatic skeleton. Owing to the higher number of nitrogen atoms and a-lone pairs, tetrazoles offer the opportunity to control structural topology through non-covalent interactions. In this perspective, the present research is focused on the investigation of various non-covalent interactions in a series of tetrazole derivatives (5a-c) incorporating a linear aliphatic chain (eight to fifteen carbon atoms) at N-2 and with a phenol moiety at the only carbon atom of the tetrazole ring. The detailed X-ray crystallographic investigations revealed the formation of various supramolecular architectures employing non-covalent interactions of a diverse nature. Further insights into these intermolecular interactions were obtained using Hirshfeld surface analysis and DFT calculations focusing on the H-bonds, C-H center dot center dot center dot pi/pi center dot center dot center dot pi interactions in the structures. These contacts have been characterized by combining the quantum theory of atoms-in-molecules (QTAIM) with the non-covalent interaction index (NCIplot). (C) 2020 Elsevier B.V. All rights reserved.

Automated summary

Tetrazoles are nitrogen-rich heterocycles with diverse medicinal properties and broad pharmaceutical potential. Research has shown that tetrazoles, due to their higher nitrogen atom content and lone pairs, offer the opportunity to control structural topology through non-covalent interactions, resulting in the formation of various supramolecular architectures.