Intramolecular interaction induced C-C cleavages in fructose conversion in polar aprotic solvents-origin of the formation of excess formic acid and oligomers

Understanding the mechanism of excess formic acid formation in the dehydration of fructose to HMF would be beneficial to improve HMF selectivity and carbon efficiency. The production of formic acid from keto- d -fructose in polar aprotic solvents, such as THF, DIO, and MTHF, and MIBK solvents without a catalyst was investigated via DFT calculations. It was found that in THF, DIO and MTHF solvents, fructose tended to generate formic acid directly with the catalysis of the intramolecular hydroxyls, especially C6-OH (terminal hydroxyl), while in MIBK, the solvent molecule could react with the intermediates produced in the process, making the barrier of production of acetic acid lower than that of formic acid. Molecular dynamics simulations showed that the lower dielectric polar aprotic solvents (THF, DIO and MTHF) could not destroy the intramolecular H-bonds of hydroxyls in fructose, which could promote the keto-enol tautomerization and hydration steps, facilitating the formation of six-member-ring transition states, which reduced the ring tension and decreased the activation energy greatly, leading to the overproduction of formic acid and oligomers. ETS-NOCV analysis further indicated that the donated electrons from C-O σ-bonds on the carbon chain of fructose made the intramolecular hydroxyls more basic, which could catalyse keto-enol tautomerization with a lower energy barrier than water molecules. To obtain more target products, such as HMF, suitable reaction environments, such as a higher polar aprotic solvent with a low boiling point or restriction of the activity of hydroxyls of fructose, might be selected to destroy the intramolecular interaction and then reduce the overproduction of formic acid and the formation of oligomers. Aprotic solvents with low β and π*, such as THF, DIO, and MTHF, led to the conversion of fructose to excess formic acid via the assistance of intramolecular OH groups.