Determination of the N-methyl stereochemistry in tropane and granatane derivatives in solution: a computational and NMR spectroscopic study

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• 作者：Ryszard Lazny ; ^{lazny@uwb.edu.pl} ; Artur Ratkiewicz ; Aneta Nodzewska ; Anna Wynimko ; Leszek Siergiejczyk
• 关键词：Tropinone ; Tropine ; Granatanone ; Amine invertomers ; Conformations in solution
• 刊名：Tetrahedron
• 出版年：2012
• 期刊代码：107_00404020
• 类别：ch
• 出版时间：5 August, 2012
• 卷：68
• 期：31
• 页码：6158-6163
• 文件大小：276 K

摘要

Tropane (8-methyl-8-azabicyclo[3.2.1]octane) and granatane (9-methyl-9-azabicyclo[3.3.1]nonane) derivatives undergo fast N-methyl inversion. The distribution of axial and equatorial N-methyl invertomers of protonated and free amine forms in aqueous and methanol solutions was studied by room and low temperature NMR spectroscopy on tropinone, tropine, granatan-3-one (pseudopelletierine or pseudopelletrierin) and 伪-granatan-3-ol. Theoretical (DFT) distributions in both gas phase and solutions are also reported. Applicability of the computational model for the studied system was verified by comparison with invertomer distributions inferred from inverse-gated ¹³C NMR experiments. Among the tested functionals, the BH&HLYP/cc-pVDZ method yields the best agreement with experiment. Moreover, accounting for orbital relaxation upon immersion in the solution was found to be of importance in order to properly reproduce observed distributions.