Scalable synthesis of 2,5-diformylfuran in single-phase continuous flow and segmented flow

Abstract

A homogeneous catalytic reaction (NaBr/H₂SO₄) was performed in single-phase continuous flow and segmented flow modes to synthesize 2,5-diformylfuran (DFF), a versatile platform molecule for bio-based polymers, organic conductors, and pharmaceutical intermediates. In the single-phase continuous flow process, the yield was suboptimal at 60%, and the gaseous dimethyl sulfide (DMS) generated as a byproduct formed irregular bubbles, which impeded process stability and presented a potential risk of atmospheric contamination upon leakage. In the second reaction, a custom-designed gas-liquid separator was introduced, which mitigated the risk of hazardous gas leakage and enhanced the process stability. However, the yield remained unsatisfactory at 73%. Subsequently, by employing the segmented flow process, DFF was synthesized with a high yield of 85% within a residence time of 30 min under steady-state flow conditions. Furthermore, by extracting and concentrating the fructose-derived 5-hydroxymethylfurfural (HMF) solution and directly applying it to the segmented flow reaction, DFF was obtained with a yield of 73% based on fructose. This integrated process is anticipated to be a viable strategy for simultaneously ensuring efficiency and safety in commercial DFF production from carbohydrate-derived feedstocks by simplifying catalyst handling, maintaining a stable operation, and effectively controlling potential harmful byproducts.