A theoretical study on the sugars' mutarotation: the epimerization 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.