A Spectroscopic Study of Nicotine Analogue 2-Phenylpyrrolidine (PPD) Using Resonant Two-Photon Ionization (R2PI), Microwave, and 2D NMR Techniques

• Published in: Journal of the American Chemical Society Vol. 131; no. 7; pp. 2638 - 2646
• Main Authors: Martin, Danielle E, Robertson, Evan G, MacLellan, Jonathan G, Godfrey, Peter D, Thompson, Christopher D, Morrison, Richard J. S
• Format: Journal Article
• Language: English
• Published: United States American Chemical Society 25.02.2009
• Subjects: Gases; Mass Spectrometry; Microwaves; Models, Chemical; Models, Molecular; Molecular Conformation; Nicotine - analogs & derivatives; Nicotine - chemistry; Nuclear Magnetic Resonance, Biomolecular - methods; Pyrrolidines - chemistry; Solutions; Thermodynamics
• ISSN: 0002-7863; 1520-5126
• DOI: 10.1021/ja807995n

Conformational preferences of the nicotine analogue 2-phenylpyrrolidine (PPD) have been studied in both gaseous and solution phases. Theoretical calculations at the MP2 and B3LYP levels point to 5−6 stable conformers which differ in three degrees of conformational freedom; torsion between the two rings, inversion at the pyrrolidine (PY) amine, and PY ring puckering, characterized using the Cremer−Pople definition for pseudorotation. Only one conformer has a trans arrangement between the amino hydrogen and the phenyl substituent. It is 6−8 kJ mol−1 more stable than the cis conformers, has a perpendicular ring arrangement, and puckers at the nitrogen atomsimilar to structures reported for nicotine. Resonant two-photon ionization (R2PI) data, including hole burn spectra, indicate only one conformer is present in the free jet expansion, and band contour analysis suggests assignment to the trans conformer. Confirmation was provided by microwave spectroscopy. Fifty-seven lines measured in the 48−72 GHz region were assigned to 206 b-type transitions and fitted to yield rotational constants within 2 MHz of MP2 values predicted for the trans conformer. The solution-phase conformers of PPD were studied using 1D and 2D 1H NMR spectroscopy and solvent-based theoretical calculations. In marked contrast to the gas phase, NMR data reveals only cis conformers present in solution. Calculations confirm increased stability for these conformers when placed in simulated chloroform or water environments. Solvent molecules are believed to disrupt a crucial N···H(ortho) stabilizing interaction present within the trans conformer.