(3R,4S)-4-(4-fluorophenyl)-3-hydroxymethyl-1-methylpiperidine: Conformation and structure monitoring by vibrational circular dichroism
(3R,4S)-4-(4-fluorophenyl)-3-hydroxymethyl-1-methylpiperidine: Conformation and structure monitoring by vibrational circular dichroism
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DOI：
10.1021/jo016094s
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发表时间：
2002-01-11
影响因子：
3.6
通讯作者：
Volka, K
中科院分区：
文献类型：
--
作者：
Bour, P;Navrátilová, H;Volka, K
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.
