Synthesis and crystal structures of five fluorinated diphenidine derivatives

Diphenidine (1a), a dissociative anaesthetic, was first reported in 2013. Since then, a number of derivatives e.g. 2-methoxphenidine (1b) have been produced by clandestine laboratories and sold as research chemicals. Fluorinated diphenidines, namely, [1-(2,6-di-fluoro-phen-yl)-2-phenyl-eth-yl]di-methyl-aza-nium chloride, C₁₆H₁₈F₂N⁺·Cl^-, (I), [1-(2,6-di-fluoro-phen-yl)-2-phenyl-eth-yl](eth-yl)aza-nium chloride di-chloro-methane hemisolvate, 2C₁₆H₁₈F₂N⁺·2Cl^-·CH₂Cl₂, (II), tert-but-yl[1-(2,6-di-fluoro-phen-yl)-2-phenyl-eth-yl]aza-nium chloride, C₁₈H₂₂F₂N⁺·Cl^-, (III), 1-[1-(2,6-di-fluoro-phen-yl)-2-phenyl-eth-yl]pyrrolidin-1-ium chloride, C₁₈H₂₀F₂N⁺·Cl^-, (IV), and 1-[1-(2,3,4,5,6-penta-fluoro-phen-yl)-2-phenyl-eth-yl]piperidin-1-ium chloride, C₁₉H₁₉F₅N⁺·Cl^-, (V), were synthesized and structurally characterized by ¹H, ¹³C and ¹⁹F NMR spectroscopy, and single-crystal X-ray diffraction. All five structures exhibit hydrogen bonding between the quaternary amine hydrogen atoms and the chlorine. The N-H⋯Cl distances for (II) and (III) range from 2.21 to 2.31 Å, whereas (I), (IV) and (V) exhibit shorter N-H⋯Cl distances (2.07-2.20 Å). Compounds (IV) and (V) include pyrrolidine and piperidine rings, respectively; the pyrrolidine ring adopts an envelope conformation whereas the piperidine ring adopts a chair conformation. The crystal packing in compounds (I)-(V) is characterized by C-H⋯π inter-actions; no π-π inter-actions are observed.