A theoretical study on the sugars' mutarotation: the epimerisation of 2-tetrahydropyranol catalysed by formamidine, benzamidine and by the 2-aminopyridine/2-iminopyridine tautomeric couple

The mutarotation of the model sugar 2-tetrahydropyranol promoted by bifunctional catalysts such as formamidine, benzamidine and 2-aminopyridine/2-iminopyridine was investigated at different computational levels. It was shown that the above catalysts react with the substrate by a concerted double proton transfer (PT), which causes the breaking of the C-O bond of the sugar ring. The occurrence of a purely basic mechanism for benzamidine and formamidine resulted unlikely both in vacuum and in benzene. A complete reaction path was proposed which takes into account the relative energy of minima and transition states as well as the catalyst dimerisation versus substrate-catalyst interactions. The processes catalysed by formamidine and benzamidine displayed nearly coincident energetics, with slightly higher PT activation energies than the previously investigated formic acid and 2-pyridone/2-hydroxypyridine systems. The catalyst tendency to dimerise turned out to be less relevant for formamidine and benzamidine than for formic acid and, especially, for 2-pyridone/2-hydroxypyridine. The 2-aminopyridine/2-iminopyridine tautomeric couple displayed two possible reaction paths very similar to those previously defined for the formamide/formamidic acid tautomeric couple, from the energetical point of view. The occurrence of relatively high PT activation energies raised the question of whether the 2-aminopyridine/2-iminopyridine couple is active as a tautomeric catalysts or by virtue of only the basic group. A possible solution to this problem was discussed. Solvent effects in benzene were shown to cause only small changes with respect to the energetics computed in vacuum.