Synthesis and crystal structures of five fluorinated diphenidine derivatives.
Ryan E Mewis, Matthew C Hulme, Jack Marron, Stuart K Langley, Oliver B Sutcliffe, Sophie L Benjamin
Acta crystallographica. Section E, Crystallographic communications March 1, 2025 DOI: 10.1107/S2056989025001288 (opens in new tab) via PubMed
Summary
AI-generated from the abstractFive fluorinated diphenidine derivatives were synthesized and their structures determined using NMR spectroscopy and X-ray crystallography. All five compounds form hydrogen bonds between their quaternary amine hydrogen atoms and chloride ions. Two compounds show N-H⋯Cl distances of 2.21–2.31 Å, while three exhibit shorter distances of 2.07–2.20 Å. The compound with a pyrrolidine ring adopts an envelope conformation, and the one with a piperidine ring adopts a chair conformation. Crystal packing in all five structures involves C-H⋯π interactions, and no π-π interactions are observed.
Study at a glance
| Characteristics | Structural characterization study Peer reviewed |
|---|---|
| Keywords | Crystal structure Diphenidine Novel psychoactive substances |
| Key finding | Five fluorinated diphenidine derivatives were synthesized and structurally characterized, all showing N-H⋯Cl hydrogen bonds and C-H⋯π interactions in their crystal packing, with no π-π interactions. |
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-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.