Efficient One-Pot Production of 5-Hydroxymethylfurfural from Glucose in an Acetone–Water Solvent

5-Hydroxymethylfurfural (HMF) is a high-value biomass-derived platform chemical derived from renewable biomass, which is a great alternative to petroleum-based chemicals; however, it cannot be produced on a large scale at present because of the limitation of a low HMF yield and costly production. In this work, an experimental study of one-pot production of HMF from glucose in an acetone–water solvent was conducted. The effects of inorganic salts (in specific, NaCl) on miscible solvents were studied because inorganic salts could affect the phase structure of solvents. We also study the influence of the ratio between Lewis acid and Brønsted acid (L/B) on the dehydration reaction. After parameter optimization experiments, up to 64.5% HMF yield was obtained at the condition of C0 = 1.25 w/v %, CAlCl3 = 1.25 w/v %, CHCl = 10 mmol·L–1, T = 160 °C, and o/a = 80/20, and the optimized L/B was 1.25 kg·mol–1. Finally, an economic and efficient HMF production process including HMF purification and catalyst recycling was proposed; the HMF product could be produced and separated with high recovery (∼88%) and purity (∼85%) in the process. Our findings and analysis would provide support for the choice of the reaction system and bifunctional catalyst synthesis in the subsequent industrial demonstration development.