Evaluation of halogen bonding proclivity of oxazole derivatives carrying multiple acceptor sites in cocrystals with perfluorinated iodobenzenes

Abstract

In order to study the competition between halogen bond acceptor sites of multifunctional N,O,X-based halogen bond acceptors (X = S, O, N or π aromatic ring) we have synthesized a family of oxazole derivatives and cocrystallized them with selected iodoperfluorinated benzenes as halogen bond donors. Out of 28 combinations, 19 experiments yielded crystals suitable for single-crystal X-ray diffraction. Structural analysis revealed that in all of the obtained cocrystals the most prominent supramolecular interaction is the I⋯N_oxazole halogen bond with relative shortening values of up to 18%, comparable to I⋯N_pyridine halogen bond shortening values. The acceptors are ditopic in 10 cocrystals and form additional I⋯N, I⋯O or I⋯π halogen bonds. A majority of cocrystals feature one donor molecule per one acceptor molecule. In order to rank the acceptor sites and establish how the electrostatic potential differences impact the supramolecular landscape around these molecules, the values of molecular electrostatic potentials (MEPs) were calculated on their optimized geometries. These calculations were in agreement with experimental observations, since the best (most negative MEP value) acceptor binding site in the series of used oxazoles is the oxazole nitrogen atom. Depending on the difference between MEP values of the oxazole oxygen atom and the peripheral functionalities, additional halogen bonds could potentially be formed with one of these acceptor sites, leading to the formation of two different types of halogen-bonded supramolecular chains.