(134f) Modeling the Aldose- Ketose Isomerization by Lewis Acids in the Gas Phase and Aqueous Media. A Detailed Mechanistic Study

Conversion of biomass-derived carbohydrates into furan derivatives is a crucial step for the manufacture of value-added chemicals and fuels from abundant biomass. Although considerable success has been achieved in the dehydration of fructose to 5-hydroxylmethylfurfural (HMF), the economics of the process depend heavily on the cost of fructose. Thereby it is extremely important to selectively convert glucose, a cheap hexose, to fructose. Researchers at the Catalysis Center for Energy Innovation have recently discovered homogeneously and heterogeneously catalyzed processes for this isomerization chemistry in aqueous phase using CrCl₃or the zeolite catalyst Sn-beta, respectively.

The aldose-ketose isomerization is a simple but mechanistically ambiguous reaction involving the formal transfer of two hydrogen atoms, from C2 and O2 to C1 and O1 of an α-hydroxy aldehyde to form the corresponding α-hydroxy ketone. In the present paper we employ electronic structure calculations and first-principles Molecular Dynamics simulations (Car-Parrinello MD with Metadynamics acceleration) to investigate the mechanism and energetics of the Lewis-acid catalyzed glucose-fructose isomerization reaction, first in the gas phase and then in solution with explicit water molecules.  Some of the findings that we shall present include:

(1) Formally, the Lewis acid catalysis favors the so-called hydride transfer mechanism from the C2 to the C1 carbon, which is activated by initial deprotonation of the hydroxyl group at the C2 carbon.

(2) By a thorough analysis of the electron charge distribution during the hydride transfer, by means of Natural Bond Orbital analysis and Electron Localization Function analysis, we find that the H transfer from C2 to C1 is more consistent with an electron-proton-electron transfer, both in the gas phase and in solution.

(3) In solution, the solvent plays a very active role in the initial deprotonation of the C2-OH and in the final proton back-donation to the C1-O, the latter being water-mediated.

(4) We present detailed free energy surfaces for all elementary steps of the reaction in solution and compare the MD-predicted equilibrium structures with those revealed by Extended X-ray Absorption Fine Structure Spectroscopy.