A theoretical study of hydrogen bonding, proton transfer and kinetic isotope effects in the dimers of 2-tetrahydropyranol and in the 2-tetrahydropyranol-H2O adducts

The catalysed isomerisation of the model sugar 2-tetrahydropyranol (2-THP) was investigated by means of DFT and ab initio calculations in vacuum. This reaction may be promoted by a second 2-THP molecule (self-catalysed proces s) or by a H2O molecule in the framework of hydrogen bonded adducts. Activa tion energies of ca. 30 and 25 kcal mol(-1) respectively were calculated, s o that the above processes are not considered to play a significant role at room temperature. A third type of reaction may take place, namely the ring opening of 2-THP catalysed by an open-chain 2-THP tautomer. This reaction displays an activation energy of ca. 16 kcal mol(-1) but requires the prese nce of a third catalytic species, capable of yielding an initial amount of open-chain tautomer. Kinetic isotope effects (KIE) associated with H/D subs titution were calculated for all considered adducts, resulting in higher ef fects for the H2O-catalysed reaction and for the reaction catalysed by an o pen-chain monomer than for the self-catalysed process. Normal-coordinate de composition analysis performed on the vibrational modes of the transition s tates showed that the calculated KIEs increase with the contribution of O-H stretching modes to the reaction coordinate and decrease with the contribu tion of the stretching of the C-O bond in the sugar ring. The analysis also showed how such contributions affect the different terms which give rise t o the KIE.