Synthesis and crystal structures of five fluorinated diphenidine derivatives

Abstract

The crystal structures of five fluorinated diphenidine mol­ecules obtained as their hydro­chloride salts are reported.

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-di­fluoro­phen­yl)-2-phenyl­eth­yl]di­methyl­aza­nium chloride, C₁₆H₁₈F₂N⁺·Cl⁻, (I), [1-(2,6-di­fluoro­phen­yl)-2-phenyl­eth­yl](eth­yl)aza­nium chloride di­chloro­methane hemisolvate, 2C₁₆H₁₈F₂N⁺·2Cl⁻·CH₂Cl₂, (II), tert-but­yl[1-(2,6-di­fluoro­phen­yl)-2-phenyl­eth­yl]aza­nium chloride, C₁₈H₂₂F₂N⁺·Cl⁻, (III), 1-[1-(2,6-di­fluoro­phen­yl)-2-phenyl­eth­yl]pyrrolidin-1-ium chloride, C₁₈H₂₀F₂N⁺·Cl⁻, (IV), and 1-[1-(2,3,4,5,6-penta­fluoro­phen­yl)-2-phenyl­eth­yl]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 inter­actions; no π–π inter­actions are observed.