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 mols. and 13C NMR 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 extn. of the evolved HMF with 2-sec-butylphenol results in the increase in the HMF selectivity for phosphate/TiO2, even in highly concd. glucose soln. These results suggest that limiting the reactions between HMF and the surface intermediates improves the efficiency of HMF prodn. [on SciFinder(R)]