title: (3R,4S)-4-(4-Fluorophenyl)-3-hydroxymethyl-1-methylpiperidine: conformation and structure monitoring by vibrational circular dichroism.
abstract: Absorption and vibrational circular dichroism (VCD) spectra of the title compound, a common intermediate in synthesis of many pharmaceuticals, were measured and analyzed in order to determine its absolute configuration and prevailing conformations. The analysis was combined with a systematic conformer search based on relative energies as well as with comparison of experimental and computed NMR shifts. The spectra were interpreted on the basis of ab initio simulations. The results indicate that the compound adopts exclusively a chair conformation of the piperidine ring with all the fluorophenyl, hydroxymethyl, and methyl substituents attached in equatorial positions. A limited rotation of the hydroxymethyl group is most consistent with the observed VCD pattern. VCD parameters were found significantly more sensitive to conformational changes than absorption or NMR. Concentration dependence of the absorption spectra indicated aggregation in concentrated solutions, but involved hydrogen bonds probably do not influence molecular conformation.
authors.affiliation: Department of Analytical Chemistry, Institute of Chemical Technology, Technická 5, 166 28 Praha 6, Czech Republic. bour@uochb.cas.cz
authors.forename: Petr
authors.initials: P
authors.lastname: Bour
authors.forename: Hana
authors.initials: H
authors.lastname: Navrátilová
authors.forename: Vladimír
authors.initials: V
authors.lastname: Setnicka
authors.forename: Marie
authors.initials: M
authors.lastname: Urbanová
authors.forename: Karel
authors.initials: K
authors.lastname: Volka
mesh_terms: D002942:Circular Dichroism; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D008968:Molecular Conformation; D010880:Piperidines / Q000737:chemistry*; D017550:Spectroscopy, Fourier Transform Infrared; D055672:Static Electricity; D013237:Stereoisomerism; D014732:Vibration
chemical_list: D010880:Piperidines