Hydrogen sulfate ionic liquid additives with aluminum chloride catalyst in ethanol were found to promote efficient (30 min) one-pot, one-step transformation of glucose into 5-ethoxymethylfurfural (5-EMF) in 37% yields. Spectroscopic measurements (FT-IR, 1H NMR) showed that ionic liquids form multiple hydrogen bonds with glucose and promote its ring opening through ionic liquid-AlCl3 complexes to enable formation of 5-EMF via 5-hydroxymethylfurfural (5-HMF). Reactions performed in dimethyl sulfoxide using (protic, aprotic) ionic liquid additives with and without AlCl3 catalyst showed that both the ionic liquid and AlCl3 were required for efficient transformation of glucose into 5-EMF. The proposed reaction mechanism for 5-EMF synthesis in the ethanol-1-butyl-3-methylimidazolium hydrogen sulfate-AlCl3 reaction system consists of ring opening of glucose to form the 1,2-enediol and dehydration to form 5-HMF that is followed by etherification to the 5-EMF product. The reaction system is effective for glucose transformation and has application to biomass-related compounds.