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

Abstract

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 process) or by a H₂O molecule in the framework of hydrogen bonded adducts. Activation energies of ca. 30 and 25 kcal mol⁻¹ respectively were calculated, so 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 presence of a third catalytic species, capable of yielding an initial amount of open-chain tautomer. Kinetic isotope effects (KIE) associated with H/D substitution were calculated for all considered adducts, resulting in higher effects for the H₂O-catalysed reaction and for the reaction catalysed by an open-chain monomer than for the self-catalysed process. Normal-coordinate decomposition analysis performed on the vibrational modes of the transition states showed that the calculated KIEs increase with the contribution of O–H stretching modes to the reaction coordinate and decrease with the contribution 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 to the KIE.