Synthesis and crystal structures of five fluorinated diphenidine derivatives

Mewis, Ryan E ORCID: https://orcid.org/0000-0002-3756-6505, Hulme, Matthew C, Marron, Jack, Langley, Stuart K ORCID: https://orcid.org/0000-0002-2241-1551, Sutcliffe, Oliver B ORCID: https://orcid.org/0000-0003-3781-7754 and Benjamin, Sophie L (2025) Synthesis and crystal structures of five fluorinated diphenidine derivatives. Acta Crystallographica Section E Crystallographic Communications, 81 (3). pp. 229-234. ISSN 2056-9890

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Abstract

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.