DFF's diverse applications in pharmaceuticals, fungicides, and polymer synthesis motivate the development of efficient production methods. This study reports the continuous-flow synthesis of DFF from 5-HMF in a packed-bed reactor. The Box-Behnken design coupled with response surface methodology (RSM) was employed to optimize the reaction parameters (catalyst, solvent, temperature, oxygen flow rate, catalyst amount) for DFF yield. Ru/Al2O3 in toluene proved to be the most effective catalyst-solvent combination. The optimal conditions for DFF production were identified as: 140 °C reaction temperature, 10 ml min-1 oxygen flow rate, and 0.15 g catalyst loading. Under these conditions, a DFF yield of 84.2% was achieved.
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