Synthesis and conformational studies on 1-aryl-cis-2,6-diphenylpiperidines

Abstract

A facile and convenient synthesis of N-aryl-cis-2,6-diphenylpiperidines was achieved via reductive amination of 1,5-diphenyl-1,5-pentanedione with aryl ammonium formate under metal-free and microwave mediated Leuckrdt Wallach reaction conditions. The gas-phase (by Density Functional Theory studies), Liquid phase (by Nuclear Magnetic Resonance spectral analysis) and solid-phase (by X-ray crystallography along with Hirshfeld and Fingerprint plot analysis) structural studies on the title compound showed that the N-aryl, C(2) and C(6) phenyl rings were preferentially oriented equatorially and piperidine ring flattened-chair conformation. Besides, the DFT calculation showed a face-to-face arrangement of N-aryl ring with adjacent phenyl rings, and they were orthogonal to mean plane of the piperidine ring. The single-crystal structure (CCDC 1415313) analysis showed that the title compound crystallized in the monoclinic crystal system with P2(1)/C space group. The crystal packing was stabilized by intermolecular C-H…π interactions. Overall, the orientation of aryl rings looks like that of elephant ears flanking the snout.