On tautomeric equilibria in the guanazole molecule. A DFT study

More than 30 guanazole tautomers, conformers, and zwitterions were calculated at the B3LYP/aug-cc-pVDZ level in vacuum and in water solution described by the IEF-PCM method. The most stable four structures were recalculated at the B3LYP/aug-cc-pVTZ level. The 1H guanazole tautomer appeared to be the only one stable in vacuum. The 4H tautomer, next stable in vacuum, is higher in energy by ca. 9.5 kcal/mol. In water (described by the IEF-PCM method), the 4H tautomer remains less stable by ca. 4.5 kcal/mol and the next most stable tautomers are disfavored by about 9 kcal/mol. Possibility of existence of and interconversion between two 1H conformers, which differ in direction of lone electron pairs of the two NH2 groups, was also considered. The interconvertion can proceed either by inversion or by rotation of one of the NH2 groups. The barrier for the invertion is only 100 cm−1 and it is overcome by the NH2 group inversion vibrational modes. Thus such a barrier is apparent rather than real. Barrier to the NH2 group rotation is equal to ca. 6 kcal/mol, and would preserve a given molecular conformation; however, the NH2 group inversion modes make this impossible. The autotropic proton shift between the two neighboring N atoms of the triazole ring was also considered; yet, the barrier for such a shift is ca. 40 kcal/mol high and is very unlikely.