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

Abstract

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 σ-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…π and π–π 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).