5-Hydroxymethylfurfural (HMF) is a key platform chemical that may be obtained from various cellulosic (biomass) derivatives. Previously, it has been shown that ionic liquids (ILs) facilitate the catalytic conversion of glucose into HMF. Herein, we demonstrate that the careful design of the IL cation leads to new ionic solvents that enhance the transformation of glucose and more complex carbohydrates into HMF significantly. InSitu NMR spectroscopy and computational modeling pinpoint the key interactions between the IL, catalyst, and substrate that account for the enhanced reactivities observed.