How the oxazole fragment influences the conformation of the tetraoxazocane ring in a cyclohexanespiro-3′-(1,2,4,5,7-tetraoxazocane): single-crystal X-ray and theoretical study

Abstract

Single crystals of (2S,5R)-2-isopropyl-5-methyl-7-(5-methylisoxazol-3-yl)cyclohexanespiro-3′-(1,2,4,5,7-tetraoxazocane), C16H26N2O5, have been studied via X-ray diffraction. The tetraoxazocane ring adopts a boat–chair conformation in the crystalline state, which is due to intramolecular interactions. Conformational analysis of the tetraoxazocane fragment performed at the B3LYP/6-31G(d,2p) level of theory showed that there are three minima on the potential energy surface, one of which corresponds to the conformation realized in the solid state, but not to a global minimum. Analysis of the geometry and the topological parameters of the electron density at the (3,−1) bond critical points (BCPs), and the charge transfer in the tetraoxazocane ring indicated that there are stereoelectronic effects in the O—C—O and N—C—O fragments. There is a two-cross hyperconjugation in the N—C—O fragment between the lone electron pair of the N atom (lpN) and the antibonding orbital of a C—O bond (σ*C—O) and vice versa between lpO and σ*C—N. The oxazole substituent has a considerable effect on the geometry and the topological parameters of the electron density at the (3,−1) BCPs of the tetraoxazocane ring. The crystal structure is stabilized via intermolecular C—H...N and C—H...O hydrogen bonds, which is unambiguously confirmed with PIXEL calculations, a quantum theory of atoms in molecules (QTAIM) topological analysis of the electron density at the (3,−1) BCPs and a Hirshfeld analysis of the electrostatic potential. The molecules form zigzag chains in the crystal due to intermolecular C—H...N interactions being electrostatic in origin. The molecules are further stacked due to C—H...O hydrogen bonds. The dispersion component in the total stabilization energy of the crystal lattice is 68.09%.