2-Pyridinethiol/2-pyridinethione tautomeric equilibrium. A comparative experimental and computational study

The gas phase and solvent dependent preference of the tautomerization between 2-pyridinethiol (2SH) and 2-pyridinethione (2S) has been assessed using variable temperature Fourier transform infrared (FTIR) experiments, as well as ab initio and density functional theory computations. No spectroscopic evidence (v_S-H stretch) for 2SH was observed in toluene, C₆D₆, heptane, or methylene chloride solutions. Although, C_s 2SH is 2.61 kcal/mol more stable than C_s 2S (CCSD(T)/cc-pVTZ//B3LYP/6-311+G(3df,2p)+ZPE), cyclohexane solvent-field relative energies (IPCM-MP2/6-311+G-(3df,2p)) favor 2S by 1.96 kcal/mol. This is in accord with the FTIR observations and in quantitative agreement with the -2.6 kcal/mol solution (toluene or C₆D₆) calorimetric enthalpy for the 2S/2SH tautomerization favoring the thione. As the intramolecular transition state for the 2S, 2SH tautomerization (2TS*) lies 25 (CBS-Q) to 30 kcal/mol (CCSD/cc-pVTZ) higher in energy than either tautomer, tautomerization probably occurs in the hydrogen bonded dimer. The B3LYP/6-311+G-(3df,2p) optimized C₂ 2SH dimer is 10.23 kcal/mol + ZPE higher in energy than the C_2h 2S dimer and is only 2.95 kcal/mol + ZPE lower in energy than the C₂ 2TS* dimer transition state. Dimerization equilibrium measurements (FTIR, C₆D₆) over the temperature range 22-63°C agree: K_eq²⁹⁸ = 165 ± 40 M^-I, ΔH = -7.0 ± 0.7 kcal/mol, and ΔS = -13.4 ± 3.0 cal/(mol deg). The difference between experimental and B3LYP/6-311+G(3df,2p) [-34.62 cal/(mol deg)] entropy changes is due to solvent effects. The B3LYP/6-311+G(3df,2p) nucleus independent chemical shifts (NICS) are -8.8 and -3.5 ppm 1 Å above the 2SH and 2S ring centers, respectively, and the thiol is aromatic. Although the thione is not aromatic, it is stabilized by the thioamide resonance. In solvent, the large 2S dipole, 2-3 times greater than 2SH, favors the thione tautomer and, in conclusion, 2S is thermodynamically more stable than 2SH in solution.