Theoretical and experimental 1H, 13C and 15N NMR studies of N-alkylation of substituted tetrazolo[1,5-a]pyridines.

The (15)N as well as (1)H and (13)C chemical shifts of nine substituted tetrazolopyridines and their corresponding tetrazolopyridinium salts have been determined by using NMR spectroscopy at the natural abundance level of all nuclei in CD(3)CN. In this paper, we report, for the first time, the N-alkylation reaction of electron deficient tetrazolopyridines. The treatment of tetrazolopyridines 5-13 with one equivalent of trialkyloxonium tetrafluoroborate leads to a mixture of two isomers, i.e. N3- and N2-alkyl tetrazolo[1,5-a]pyridinium salts. It has been observed that the N3-isomer is always the major isomer, except in the case of the CF(3) substituent, where the two isomers are obtained in the same amount. The quaternary tetrazolopyridinium nitrogen N3 is shielded by around 100 ppm (parts per million) with respect to the parent tetrazolopyridine. Experimental data are interpreted by means of density functional theory (DFT) calculations, including solvent-induced effects, within the conductor-like polarizable continuum model (CPCM). Good agreements between theoretical and experimental (1)H, (13)C and (15)N NMR were found. The combination of multinuclear magnetic resonance spectroscopy with gauge including atomic orbital (GIAO) DFT calculations is a powerful tool in the structural elucidation for both neutral and cationic heterocycles and in the determination of the orientation of N-alkylation of tetrazolopyridines.