Site of protonation of nicotine and nornicotine in the gas phase: pyridine or pyrrolidine nitrogen?
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 Nsp(3) protonation in water, in the gas phase nornicotine is protonated on the pyridine nitrogen, because the effects of an intramolecular CH.Nsp(3) hydrogen bond and of the polarizability of the 3-(pyrrolidin-2-yl) substituent add up on the Nsp(2) basicity, while the polarizability effect of the 2-(3-pyridyl) substituent on the Nsp(3) basicity is canceled by its field/inductive electron-withdrawing effect. The same structural effects operate on the Nsp(3) and Nsp(2) 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 Nsp(3) and Nsp(2) protonated forms.
Laboratoire de Spectrochimie (EA 1149), Université de Nantes, 2, rue de la Houssinière, BP 92208, 44322 Nantes Cedex 3, France.
Jérôme
J
Graton
Michel
M
Berthelot
Jean-François
JF
Gal
Sandrine
S
Girard
Christian
C
Laurence
Jacques
J
Lebreton
Jean-Yves
JY
Le Questel
Pierre-Charles
PC
Maria
Petr
P
Naus
D001665:Binding Sites; D005740:Gases; D008956:Models, Chemical; D008958:Models, Molecular; D008968:Molecular Conformation; D009538:Nicotine / Q000031:analogs & derivatives* / Q000737:chemistry*; D009584:Nitrogen / Q000737:chemistry*; D011522:Protons; D055672:Static Electricity; D013816:Thermodynamics
D005740:Gases; D011522:Protons; D009538:Nicotine; C005311:nornicotine; D009584:Nitrogen