In most of the reported studies for the production of 5-HMF from biomass in ionic liquids, the 5-HMF was obtained in solution, and the yield of 5-HMF was deter­mined with HPLC or GC without isolation. However, it is of great importance to develop an efficient isolation method for the synthesis of 5-HMF. Wei et al. [102] developed a novel entrainer-intensified vacuum reactive distillation process for the separation of 5-HMF from ionic liquids 1-octyl-3-methylimidazolium chloride ([OMIM][Cl]) that involves heating reaction mixtures under vacuum (ca.300 Pa) to 150-180 °C under a flow of an entrainer (nitrogen), and 95 % of the 5-HMF was recovered from the reaction mixture after 10 min at 180 °C. However, distillation is not a favorable method for the separation of 5-HMF from ionic liquids system, not only because both 5-HMF and ionic liquids have high boiling point, but also because 5-HMF is very reactive and tends to decompose at high temperatures.

Monosaccharides such as fructose and glucose have polarities similar to those of ionic liquids, while 5-HMF has different properties from ionic liquids, which allows separation of 5-HMF from ionic liquids by liquid-liquid extraction. However, an efficient separation solvent is needed to reduce the amount of solvent (low solvent/ feed ratio) required for extraction of 5-HMF from ionic liquid solutions. An ideal extraction solvent should be immiscible with ionic liquids and have a large affinity for 5-HMF. Further, it should be separable from the product, with a method that does not require a large amount of energy. Therefore, it should have a relatively low boiling point to avoid thermal decomposition or polymerization of the 5-HMF and to reduce the energy costs. Many organic solvents such as MIBK (methyl isobutyl ketone) [53], ethyl acetate [20, 63], diethyl ether [29, 45], THF [84], and acetone [60] have been reported to be efficient extraction solvents. Qi et al. [20] tested the separation of 5-HMF from [BMIM][Cl] after reaction by extracting five times with 8 ml of ethyl acetate after 0.5 g of water was added to reduce the viscosity of the ionic liquid. [BMIM][Cl] and fructose were found to be insoluble in ethyl acetate and 5-HMF was the sole product in ethyl acetate phase, and above 95 % of 5-HMF was separated from the reaction mixture after five times extraction. Hu et al. [36] presented 5-HMF synthesis from fructose in a biphasic system of ethyl acetate and choline chloride (ChoCl) with citric acid, and the continuous in-situ extraction of 5-HMF with ethyl acetate led to a 15 % enhancement in the 5-HMF yield in comparison with a neat ionic liquid. For larger-scale production, more efforts have to be made on efficient separation techniques.