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%.