Green and efficient one-pot synthesis of the bio-based platform molecule 4-hydroxymethyl-2-furfural on a multigram scale

Abstract

This study outlines a detailed process development of dendroketose preparation and its conversion to the bio-based platform molecule 4-hydroxymethyl-2-furfural (4-HMF) through a dehydration reaction in water as a green and sustainable solvent. Initially, dendroketose was synthesized via a monoaldol reaction of dihydroxyacetone (DHA) as a glycerin- or CO-based product, simply using NaOH as a catalyst at various DHA concentrations. We successfully demonstrate preparation of a high loading of dendroketose, resulting in an ecological factor (E-factor, EF) of EF = 1. For the subsequent dehydration of dendroketose to 4-HMF, an optimized process was designed after evaluating various solvents and catalysts. Saturated aqueous NaCl solution offered the highest 4-HMF:5-HMF reaction selectivity of 95%. Optimal conditions for the 4-HMF synthesis were determined as 0.25 M HCl, 80 °C, 100 g per L dendroketose, and a reaction time of 120 minutes, achieving an 80% selectivity towards the formation of total HMF. In addition, scale-up experiments on an elevated lab scale of 100 g dendroketose in combination with a tailor-made reactor set-up for smooth product removal confirmed the identified preferred process conditions, leading to an 89% reaction yield over nine cycles, with an isolated 4-HMF yield of 76%, a purity of 92% and an EF = 0.67. These results also underline the potential of this process and reactor set-up for efficient and scalable 4-HMF production, with further optimization opportunities identified in salt selection, catalyst loadings, and process control strategies.