Formation of 5‑(Hydroxymethyl)furfural by Stepwise Dehydration over TiO₂ with Water-Tolerant Lewis Acid Sites

The reaction mechanism for the formation of 5-(hydroxymethyl)­furfural (HMF) from glucose in water over TiO₂ and phosphate-immobilized TiO₂ (phosphate/TiO₂) with water-tolerant Lewis acid sites was studied using isotopically labeled molecules and ¹³C nuclear magnetic resonance measurements for glucose adsorbed on TiO₂. Scandium trifluoromethanesulfonate (Sc­(OTf)₃), a highly active homogeneous Lewis acid catalyst workable in water, converts glucose into HMF through aldose–ketose isomerization between glucose and fructose involving a hydrogen transfer step and subsequent dehydration of fructose. In contrast to Sc­(OTf)₃, Lewis acid sites on bare TiO₂ and phosphate/TiO₂ do not form HMF through the isomerization–dehydration route but through the stepwise dehydration of glucose via 3-deoxyglucosone as an intermediate. Continuous extraction of the evolved HMF with 2-<i>sec</i>-butylphenol results in the increase in the HMF selectivity for phosphate/TiO₂, even in highly concentrated glucose solution. These results suggest that limiting the reactions between HMF and the surface intermediates improves the efficiency of HMF production