Site of Protonation of Nicotine and Nornicotine in the Gas Phase: Pyridine or Pyrrolidine Nitrogen?

Publisher Website
Google Scholar
Abstract
The gas-phase basicities (GBs) of nornicotine, nicotine, and model pyrrolidines have been measured by FT-ICR. These experimental GBs are compared with those calculated (for the two sites of protonation in the case of nicotine and nornicotine) at the B3LYP/6-311+G(3df,2p)//B3LYP/6-31G(d,p) level, or those estimated from substituent effects on the GBs of 2-substituted pyrrolidines, 2-substituted N-methylpyrrolidines, and 3-substituted pyridines. It is found that, in contrast to the Nsp3 protonation in water, in the gas phase nornicotine is protonated on the pyridine nitrogen, because the effects of an intramolecular CH···Nsp3 hydrogen bond and of the polarizability of the 3-(pyrrolidin-2-yl) substituent add up on the Nsp2 basicity, while the polarizability effect of the 2-(3-pyridyl) substituent on the Nsp3 basicity is canceled by its field/inductive electron-withdrawing effect. The same structural effects operate on the Nsp3 and Nsp2 basicities of nicotine, but here, the polarizability effect of the methyl group puts the pyrrolidine nitrogen basicity very close to that of pyridine. Consequently, protonated nicotine is a mixture of the Nsp3 and Nsp2 protonated forms.
Keywords