Method for separating 5-hydroxymethylfurfural from partially purified product solution of dehydration reaction of six-carbon (C6) carbohydrate

Abstract

The present invention relates to an apparatus and a method for separating 5-hydroxymethylfurfural from a partially purified product solution (PPPS) of a dehydration reaction of a six-carbon (C6) carbohydrate by means of simulated moving bed chromatography technology, and the PPPS substantially contain no humins. In one embodiment, the present invention relates to first removing a hydrophobic solvent from the PPPS, and then treating same in an improved low-temperature three-section SMB chromatography apparatus to separate HMF from an aprotic polar solvent. In another embodiment, the present invention relates to directly subjecting the PPPS to a treatment of an improved low-temperature four-section SMB chromatography apparatus, thereby separating HMF, the hydrophobic solvent, and the aprotic polar solvent in a single chromatography system. The operating temperatures of the SMB chromatography apparatus and method are both controlled below 80°C to avoid unwanted chemical reactions of HMF caused by high temperature. The SMB chromatography apparatus and method each have one section configured to be not directly connected to the remaining sections, so as to allow the respective introduction of two different solvents into different sections, thereby effectively separating and desorbing HMF and other components, saving on the solvent amount, and reducing the operational volume of subsequent steps.

Description

A method for separating 5-hydroxymethylfurfural from a partially purified product solution of a six-carbon (C6) carbohydrate dehydration reaction Technical Field

[0001] The present invention relates to a method and apparatus for separating 5-hydroxymethylfurfural from a partially purified product solution (PPPS) from a six-carbon (C6) carbohydrate dehydration reaction, wherein the PPPS is substantially free of humins. In particular, the present invention relates to a method and apparatus for separating 5-hydroxymethylfurfural from the PPPS using simulated moving bed chromatography. Background Art

[0002] 5-Hydroxymethylfurfural is a biomass-derived platform chemical, primarily prepared from six-carbon (C6) carbohydrates through hydrolysis and dehydration reactions in different systems. Its derivatives can be further developed into various resins, polymers, solvents, and fuels, and therefore have the potential to replace or substitute petrochemical materials.

[0003] The dehydration reaction of hexoses is primarily affected by the catalyst, temperature, and solvent. Acidic catalysts are typically used in various solvents, with the solvent significantly impacting HMF conversion. Dimethyl sulfoxide (DMSO) has been shown to offer high conversion rates, but subsequent separation of HMF from the product solution presents another challenge. Numerous studies have attempted to separate HMF using solvent extraction methods such as MIBK, molecular distillation, or adsorption, with adsorption considered the most cost-effective technique.

[0004] As shown in the reaction flow diagram of Figure 1, after hexose dehydration to HMF, levulinic acid (LA) and formic acid (FA) often undergo secondary hydration with water to form levulinic acid (LA) and formic acid (FA), which then copolymerize with hexose to form humins. The presence of humins often deactivates or renders adsorbents in downstream purification processes inactive. To address this issue, the present inventors have employed a hydrophobic solvent with a log P (octanol-water partition coefficient) between 2.45 and 3.00 and a solubility in water below 0.100 wt% as an extractant to extract the product solution generated by the hexose dehydration reaction. This results in HMF remaining in the organic phase of the hydrophobic solvent, while the humins remain in the aqueous phase. This allows for the successful removal of the humin impurities through a simple phase separation step.

[0005] However, the product solution obtained after the above-mentioned partial purification process still contains three main components: HMF, a hydrophobic solvent (such as toluene), and an aprotic polar solvent (such as DMSO), as well as trace amounts of other byproducts such as LA. In addition, HMF has the characteristics of a low melting point, a high boiling point, and easy solubility with other substances. As a result, it is difficult to effectively separate HMF from its byproducts using common separation methods such as crystallization, distillation, and extraction. In particular, the high boiling point of aprotic polar solvents such as DMSO and HMF is extremely sensitive to temperature, making the separation of HMF and solvents face many problems. Therefore, the relevant industry urgently needs a device and method for low-temperature separation of HMF and byproducts to ensure that HMF can become a sustainable biomass-derived platform chemical in an economically competitive manner.

[0006] Summary of the Invention

[0007] The present invention is the first to disclose that the partially purified product solution (PPPS) obtained from the partial purification of the product solution of a hexahydrocarbon dehydration reaction can be used to effectively separate three main components: HMF, a hydrophobic solvent, and an aprotic polar solvent, using an improved low-temperature simulated moving bed (SMB) chromatography apparatus. Compared to conventional preparative-scale batch chromatography techniques, such as high-performance liquid chromatography (HPLC), the continuous operation of the improved low-temperature SMB chromatography technique of the present invention not only effectively increases overall equipment capacity and enhances the effectiveness of the stationary phase adsorbent, but also reduces operating costs and mobile phase solvent consumption. More importantly, the improved low-temperature SMB chromatography apparatus of the present invention can operate under mild conditions such as low temperature and low humidity, which are friendly to HMF. This overcomes the existing problems of ineffective HMF separation and avoids side reactions during the separation process, ultimately allowing the isolation of high-purity HMF crystals.

[0008] Of particular note, in the improved low-temperature three-zone SMB chromatography device of the present invention, the first zone is not directly connected to the second zone. Preferably, the first zone is fluidically disconnected from the second and third zones, while the second zone is fluidically connected to the third zone. This structural configuration allows two solvents with different polarities or other properties to be introduced into the first zone and the second and third zones, respectively, effectively separating and desorbing HMF from aprotic polar solvents. This also saves solvent usage and reduces the operating volume of subsequent steps. Furthermore, the improved low-temperature three-zone SMB chromatography device of the present invention is equipped with a temperature control assembly to maintain the operating temperature of the entire device below 80°C to prevent undesirable chemical reactions of HMF caused by high temperatures, thereby improving HMF recovery.

[0009] Therefore, according to a first embodiment of the present invention, a modified low-temperature three-zone simulated moving bed (SMB) chromatography apparatus is provided. The apparatus is used to process the mixed solution obtained after removing the hydrophobic solvent from the PPPS, which contains 5-hydroxymethylfurfural (HMF) and an aprotic polar solvent, and to separate HMF from the mixed solution. The modified low-temperature three-zone SMB chromatography apparatus comprises:

[0010] The first, second, and third sections each have at least one chromatography column and are filled with a stationary phase composed of a polar adsorbent, wherein the first section is configured not to be directly connected to the second and third sections, and wherein a second wash end and a purge end for feeding and discharging a second polar wash agent are respectively provided upstream and downstream of the first section, a first wash end for feeding a first non-polar wash agent is provided upstream of the second section, a raw material feed port is provided between the second and third sections as an inlet for the mixed liquid, and a raffinate end is provided downstream of the third section as an outlet for separated HMF, and wherein flow control components are provided at the first wash end, the second wash end, and the raw material feed port, such that the relative volume flow rates of the first non-polar wash agent and the stationary phase in the second and third sections are set to satisfy the following formula (1):

[0011] Wherein m2 and m3 are the relative volume flow rates of the first non-polar eluent and the stationary phase in the second section and the third section, respectively, K A and K B are the retention constants obtained by washing HMF and the aprotic polar solvent in the simulated moving bed with the first non-polar washing agent; and

[0012] A temperature control component is used to control the operating temperature of the chromatography device to be lower than 80°C.

[0013] According to a second embodiment of the present invention, a method for separating 5-hydroxymethylfurfural (HMF) from PPPS is provided, wherein the PPPS comprises an aprotic polar solvent, a hydrophobic solvent, and HMF, and is substantially free of humins and water. The aprotic polar solvent has a substantially higher polarity than HMF, and the HMF has a substantially higher polarity than the hydrophobic solvent. This method involves first removing the hydrophobic solvent from the PPPS, and then subjecting the PPPS to a modified low-temperature three-zone SMB chromatography to separate the HMF from the aprotic polar solvent. The method comprises the following steps:

[0014] A) removing the hydrophobic solvent from the partially purified product solution to obtain a mixed solution comprising HMF and the aprotic polar solvent and substantially free of humins and water;

[0015] B) providing a modified low-temperature three-section simulated moving bed, comprising, in sequence, a first section, a second section, and a third section, each of the sections having at least one chromatography column and filled with a stationary phase composed of a polar adsorbent, wherein the first section is configured not to be directly connected to the second and third sections; and a second wash end and a wash end located upstream and downstream of the first section, for feeding and discharging a second polar wash agent, respectively; a first wash end located upstream of the second section, for feeding a first non-polar wash agent; a raw material feed port located between the second section and the third section, for feeding the partially purified product solution; and a raffinate end located downstream of the third section, serving as an outlet for separated HMF;

[0016] C) feeding the mixed liquor into the improved low-temperature three-section simulated moving bed through the raw material feed port at an operating temperature below 80° C., while causing the first non-polar fluid wash to flow sequentially through the second section and the third section, and causing the stationary phase to simulate movement in a direction opposite to the flow direction of the first non-polar fluid wash, wherein the relative volume flow rates of the first non-polar fluid wash and the stationary phase in the second section and the third section are set to satisfy the following formula (1):

[0017] Wherein m2 and m3 are the relative volume flow rates of the first non-polar eluent and the stationary phase in the second section and the third section, respectively, K A and K B retention constants obtained by washing HMF and the aprotic polar solvent with the first non-polar washing agent in the simulated moving bed, such that HMF moves to the raffinate end with the first non-polar washing agent, and the aprotic polar solvent moves to the first section; and

[0018] D) collecting HMF and a first non-polar wash stream from the raffinate end, and separating HMF from the first non-polar wash stream.

[0019] On the other hand, since the polarity of the hydrophobic solvent and the aprotic polar solvent in the PPPS differ significantly, while HMF has a polarity between these two. Therefore, these three components exhibit different retention behaviors when passing through the polar or nonpolar stationary phase of the SMB. Therefore, by designing a modified low-temperature four-segment SMB chromatography device specifically for processing PPPS, these three main components can be enriched in different segments of the SMB, thereby achieving multi-component separation within a single system. In the modified low-temperature four-segment SMB chromatography device of the present invention, segment 0 is configured not to be directly connected to segment 1. Preferably, segment 0 is fluidically disconnected from segments 1, 2, and 3, while segments 1, 2, and 3 are fluidically connected. This structural configuration allows two solvents of different polarity or other properties to be introduced into segment 0 and segments 1, 2, and 3, respectively, to effectively separate and desorb HMF and other components, thereby saving solvent usage and reducing the operating volume of subsequent steps. The improved low-temperature four-zone SMB chromatography apparatus disclosed herein also features a temperature control assembly for maintaining the operating temperature of the entire apparatus below 80°C. This prevents undesirable chemical reactions of HMF caused by high temperatures, thereby improving HMF recovery. Whether using normal-phase or reversed-phase chromatography columns, the improved low-temperature four-zone SMB chromatography apparatus disclosed herein can successfully separate the three main components of HMF: hydrophobic solvent, and aprotic polar solvent, thereby directly isolating HMF from PPPS.

[0020] Therefore, according to a third embodiment of the present invention, a modified low-temperature four-segment simulated moving bed (SMB) chromatography apparatus is provided, wherein the SMB is composed of several normal phase chromatography columns. This apparatus is suitable for directly processing the PPPS, enabling separation of HMF, a hydrophobic solvent, and an aprotic polar solvent in a single chromatography apparatus. The apparatus comprises:

[0021] The 0th, 1st, 2nd and 3rd sections each have at least one chromatography column and are filled with a stationary phase composed of a polar adsorbent, wherein the 0th section is configured not to be directly connected to the 1st, 2nd and 3rd sections, and wherein a second flow washing end and a cleaning end for feeding and discharging a second polar flow washing agent are respectively provided upstream and downstream of the 0th section, a first flow washing end for feeding a first non-polar flow washing agent is provided upstream of the 1st section, and an extraction end is provided between the 1st section and the 2nd section. The first wash end, the second wash end, and the raw material feed inlet are provided as the outlet of the separated HMF, a raw material feed inlet is provided between the second section and the third section as the inlet of the partially purified product solution, and a raffinate end is provided downstream of the third section as the outlet of the hydrophobic solvent after separation, and flow control components are provided at the first wash end, the second wash end, and the raw material feed inlet, so that the relative volume flow rates of the first non-polar wash agent and the stationary phase in the second section and the third section are set to satisfy the following formula (1):

[0022] Wherein m2 and m3 are the relative volume flow rates of the first non-polar eluent and the stationary phase in the second section and the third section, respectively, K A and K B are the retention constants obtained by washing the hydrophobic solvent and HMF in the simulated moving bed with the first non-polar wash solvent, respectively, and the relative volume flow rates of the second polar wash solvent and the stationary phase in the 0th section are set to satisfy the following formula (3): K C o ≦m o ………(3)

[0023] where K C o represents the Henry constant of the aprotic polar solvent in the 0th segment, m o represents the relative volume flow rates of the second polar eluent and the stationary phase in the 0th section; and

[0024] A temperature control component is used to control the operating temperature of the chromatography device to be lower than 80°C.

[0025] According to a fourth embodiment of the present invention, a modified low-temperature four-zone simulated moving bed (SMB) chromatography apparatus is provided, wherein the SMB is composed of multiple reversed-phase chromatography columns. This apparatus is suitable for directly processing the PPPS, enabling separation of HMF, a hydrophobic solvent, and an aprotic polar solvent in a single chromatography apparatus. The apparatus comprises:

[0026] The 0th, 1st, 2nd and 3rd sections each have at least one chromatography column and are filled with a stationary phase composed of a non-polar adsorbent, wherein the 0th section is configured not to be directly connected to the 1st, 2nd and 3rd sections, and wherein a second flow washing end and a cleaning end for feeding and discharging a second flow washing agent are respectively provided upstream and downstream of the 0th section, a first flow washing end for feeding a first polar flow washing agent is provided upstream of the 1st section, and an extraction end is provided between the 1st section and the 2nd section. The first end of the second section is used as an outlet for the HMF after separation, a raw material feed port is provided between the second section and the third section as an inlet for the partially purified product solution, and a raffinate end is provided downstream of the third section as an outlet for the aprotic polar solvent after separation, and flow control components are provided at the first wash end, the second wash end, and the raw material feed port, so that the relative volume flow rates of the first polar wash solvent and the stationary phase in the second section and the third section are set to satisfy the following formula (1):

[0027] Wherein m2 and m3 are the relative volume flow rates of the first polar eluent and the stationary phase in the second section and the third section, respectively, K A and K B are the retention constants obtained by washing the aprotic polar solvent and HMF in the simulated moving bed with the first polarity washing agent, respectively, and the relative volume flow rate of the second washing agent and the stationary phase in the 0th section is set to satisfy the following formula (3): K C o ≦m o ………(3)

[0028] where K C o represents the Henry constant of the hydrophobic solvent in the 0th segment, m o represents the relative volume flow rates of the second eluent and the stationary phase in the 0th segment; and

[0029] A temperature control component is used to control the operating temperature of the chromatography device to be lower than 80°C.

[0030] According to a fifth embodiment of the present invention, a modified low-temperature four-segment simulated moving bed (SMB) chromatography method is provided, wherein the SMB is composed of multiple normal phase chromatography columns. This method involves directly subjecting the PPPS to four-segment SMB normal phase chromatography, thereby achieving separation of HMF, a hydrophobic solvent, and an aprotic polar solvent in a single chromatography system. The method comprises:

[0031] A) providing a modified low-temperature four-zone simulated moving bed, comprising, in sequence, a 0th zone, a 1st zone, a 2nd zone, and a 3rd zone, each of the zones having at least one chromatography column and filled with a stationary phase composed of a polar adsorbent, wherein the 0th zone is configured to be not directly connected to the 1st, 2nd, and 3rd zones; and a second wash end and a wash end located upstream and downstream of the 0th zone, for feeding and discharging a second polar wash agent, respectively; a first wash end located upstream of the 1st zone, for feeding a first non-polar wash agent; an extraction end located between the 1st zone and the 2nd zone, serving as an outlet for separated HMF; a raw material feed inlet located between the 2nd zone and the 3rd zone, for feeding the partially purified product solution; and a raffinate end located downstream of the 3rd zone, serving as an outlet for the separated hydrophobic solvent;

[0032] B) feeding the partially purified product solution into the improved low-temperature four-section simulated moving bed through the raw material feed port at an operating temperature below 80° C., while causing the first non-polar flow detergent to flow through the first section, the second section, and the third section in sequence, and causing the stationary phase to simulate movement in a direction opposite to the flow direction of the first non-polar flow detergent, wherein the relative volume flow rates of the first non-polar flow detergent and the stationary phase in the second section and the third section are set to satisfy the following formula (1):

[0033] Wherein m2 and m3 are the relative volume flow rates of the first non-polar eluent and the stationary phase in the second section and the third section, respectively, K A and K B are the retention constants obtained by washing the hydrophobic solvent and HMF in the simulated moving bed with the first non-polar washing agent, and the relative volume flow rates of the second polar washing agent and the stationary phase in the 0th section are set to satisfy the following formula (3): K C o ≦m o ………(3)

[0034] where K C o represents the Henry constant of the aprotic polar solvent in the 0th segment, m o represents the relative volume flow rates of the second polar eluent and the stationary phase in the 0th section, such that HMF moves to the extraction end, and the aprotic polar solvent and the hydrophobic solvent move to the 0th section and the 3rd section, respectively; and

[0035] C) collecting HMF and the first non-polar eluent from the extraction end, and separating HMF from the first non-polar eluent.

[0036] According to a sixth embodiment of the present invention, a modified low-temperature four-segment simulated moving bed (SMB) chromatography method is provided, wherein the SMB is composed of multiple reversed-phase chromatography columns. This method involves directly subjecting the PPPS to four-segment SMB reversed-phase chromatography, thereby achieving separation of HMF, a hydrophobic solvent, and an aprotic polar solvent in a single chromatography system. The method comprises:

[0037] A) providing a modified low-temperature four-zone simulated moving bed, comprising, in sequence, a 0th zone, a 1st zone, a 2nd zone, and a 3rd zone, each of the zones having at least one chromatography column and filled with a stationary phase composed of a non-polar adsorbent, wherein the 0th zone is configured to be not directly connected to the 1st, 2nd, and 3rd zones; and a second wash end and a wash end located upstream and downstream of the 0th zone, for feeding and discharging a second wash agent, respectively; a first wash end located upstream of the 1st zone, for feeding a first polar wash agent; an extraction end located between the 1st zone and the 2nd zone, serving as an outlet for separated HMF; a raw material feed inlet located between the 2nd zone and the 3rd zone, for feeding the partially purified product solution; and a raffinate end located downstream of the 3rd zone, serving as an outlet for the separated aprotic polar solvent;

[0038] B) feeding the partially purified product solution into the improved low-temperature four-section simulated moving bed through the raw material feed port at an operating temperature below 80° C., while causing the first polarity flow detergent to flow through the first section, the second section, and the third section in sequence, and causing the stationary phase to simulate movement in a direction opposite to the flow direction of the first polarity flow detergent, wherein the relative volume flow rates of the first polarity flow detergent and the stationary phase in the second section and the third section are set to satisfy the following formula (1):

[0039] Wherein m2 and m3 are the relative volume flow rates of the first polar eluent and the stationary phase in the second section and the third section, respectively, K A and K B are the retention constants obtained by washing the aprotic polar solvent and HMF with the first polar washing agent in the simulated moving bed, respectively, and the relative volume flow rates of the second washing agent and the stationary phase in the 0th section are set to satisfy the following formula (3): K C o ≦m o ………(3)

[0040] where K C o represents the Henry constant of the hydrophobic solvent in the 0th segment, m orepresents the relative volume flow rates of the second eluent and the stationary phase in the 0th section, such that HMF moves to the extraction end, and the hydrophobic solvent and the aprotic polar solvent move to the 0th section and the 3rd section, respectively; and

[0041] C) collecting HMF and the first polar washing agent from the extraction end, and separating HMF from the first polar washing agent.

[0042] In a preferred embodiment, the chromatography apparatus and method further comprises a clean-in-place (CIP) section that is configured to be fluidically isolated from the rest of the SMB to allow a first flow of wash solvent to flow through the CIP section to regenerate the stationary phase.

[0043] In a preferred embodiment, the aprotic polar solvent is selected from the group consisting of dimethyl sulfoxide (DMSO), dimethylacetamide (DMAC), dimethylformamide (DMF), methyl pyrrolidone (NMP), and combinations thereof. In a more preferred embodiment, the aprotic polar solvent is selected from DMSO.

[0044] In a preferred embodiment, the hydrophobic solvent is selected from benzene solvents, more preferably selected from toluene. BRIEF DESCRIPTION OF THE DRAWINGS

[0045] FIG1 shows a conventional method for producing HMF and by-products from the dehydration reaction of six-carbon (C6) carbohydrates.

[0046] FIG2 is a schematic diagram of the manufacturing process of the partially purified product solution of the present invention.

[0047] FIG3 is a flow chart of the first method for separating HMF according to the present invention.

[0048] FIG4 is a schematic structural diagram of an improved low-temperature three-section simulated moving bed chromatography apparatus according to an embodiment of the present invention.

[0049] FIG5 is a flow chart of a second method for separating HMF according to the present invention.

[0050] FIG6 is a schematic structural diagram of an improved low-temperature four-segment simulated moving bed chromatography apparatus according to an embodiment of the present invention.

[0051] FIG. 7A is a calibration curve of HMF according to a preparation example of the present invention.

[0052] FIG. 7B is a DMSO calibration curve according to a preparation example of the present invention.

[0053] FIG. 7C is a LA calibration curve according to a preparation example of the present invention.

[0054] 8A-8C are photographs taken after the product solution was extracted with toluene, showing a relatively transparent hydrophobic phase and a dark lower aqueous phase.

[0055] FIG9 shows the functional relationship between temperature (horizontal axis) and HMF recovery (vertical axis) at different toluene / product solution volume ratios.

[0056] FIG. 10A is a graph showing the activity coefficients of toluene and DMSO according to an embodiment of the present invention.

[0057] FIG. 10B is a temperature-composition phase diagram of a two-component mixture of toluene and DMSO according to an embodiment of the present invention.

[0058] FIG. 11A is a temperature-composition phase diagram of a two-component toluene and DMSO at different pressures according to an embodiment of the present invention.

[0059] FIG. 11B is an XY phase diagram of a binary component of toluene and DMSO at different pressures according to an embodiment of the present invention.

[0060] FIG. 12 is a HPLC / UV analysis chart of a three-segment simulated moving bed eluent according to an embodiment of the present invention.

[0061] FIG13 is an HPLC / UV analysis chart of the washing liquid of the three-segment simulated moving bed according to another embodiment of the present invention.

[0062] FIG. 14 is an HPLC / UV analysis chart of a three-segment simulated moving bed eluent according to another embodiment of the present invention.

[0063] FIG. 15A is a graph showing the activity coefficients of two components of methanol and DMSO according to one embodiment of the present invention.

[0064] 15B is a temperature-composition phase diagram of a two-component methanol and DMSO according to an embodiment of the present invention.

[0065] FIG. 16A is a temperature-composition phase diagram of a two-component structure of methanol and DMSO at different pressures according to an embodiment of the present invention.

[0066] FIG. 16B is an XY phase diagram of a binary component of methanol and DMSO at different pressures according to an embodiment of the present invention.

[0067] FIG17 is a normal phase chromatography chromatogram using ethyl acetate as the eluent according to one embodiment of the present invention.

[0068] FIG18 is a normal phase chromatography chromatogram using methanol as the eluent according to one embodiment of the present invention.

[0069] FIG19 is a schematic structural diagram of an improved low-temperature four-segment simulated moving bed normal phase chromatography apparatus according to a specific example of the present invention.

[0070] FIG20 is a reverse phase chromatography chromatogram using 5% methanol aqueous solution as the eluent according to one embodiment of the present invention.

[0071] FIG21 is a reverse phase chromatography chromatogram using methanol as the eluent according to one embodiment of the present invention.

[0072] FIG22 is a schematic structural diagram of an improved low-temperature four-segment simulated moving bed reverse phase chromatography apparatus according to one embodiment of the present invention.

[0073] Explanation of symbols:

[0074] 1 Hydrophobic phase liquid

[0075] 2 aqueous phase liquid

[0076] 30 temperature control components

[0077] 40 flow control components

[0078] D1 first flow washing end

[0079] D2 second flow washing end

[0080] W cleaning end

[0081] F Raw material feed port

[0082] E extraction end

[0083] R extraction end. DETAILED DESCRIPTION

[0084] The present invention relates to the separation of 5-hydroxymethylfurfural (HMF) from a partially purified product solution obtained by the dehydration reaction of a six-carbon (C6) carbohydrate. As shown in Figure 1, the dehydration reaction of the C6 carbohydrate produces HMF and water. Water then reacts with HMF to produce levulinic acid (LA) and formic acid (FA). Levulinic acid, formic acid, and water polymerize, and then copolymerize with HMF to produce humins. Therefore, after this conventional dehydration reaction, the resulting product solution contains the target product HMF, an aprotic polar solvent such as DMSO, water, and unreacted C6 carbohydrate, as well as byproducts such as LA, FA, and humins. "Humins" herein refer to the primarily amorphous oligomeric or polymeric byproducts produced by the dehydration reaction of the C6 carbohydrate, which typically exhibit a dark color.

[0085] Preparation of Partially Purified Product Solution (PPPS).

[0086] As used herein, the term "partially purified product solution of a six-carbon (C6) carbohydrate dehydration reaction," or simply "partially purified product solution (PPPS)," refers to the solution obtained after the product solution has been subjected to one or more steps for enriching HMF, as described below. These steps include adding a specific proportion of water to the product solution and then extracting it with a hydrophobic solvent to remove humins. The PPPS thus prepared primarily comprises the aprotic polar solvent, the hydrophobic solvent, and HMF, and may also contain trace amounts of LA and FA, and is substantially free of humins and water. The phrase "substantially free of humins and water" herein means that the amounts of humins and water present in the partially purified product solution do not materially affect the purification process disclosed herein, thereby ultimately isolating high-purity HMF crystals. The water content can be measured using a Karl Fischer moisture titrator, the humins can be qualitatively determined by observing the color of the liquid, and the contents of other components such as HMF can be quantitatively analyzed using HPLC.

[0087] As used herein, the term "aprotic polar solvent" includes dimethyl sulfoxide (DMSO), dimethylacetamide (DMAC), dimethylformamide (DMF), methylpyrrolidone (NMP), and combinations thereof. The dehydration reaction of the six-carbon carbohydrate is carried out in the aprotic polar solvent, preferably in DMSO. The six-carbon carbohydrate is preferably selected from the group consisting of fructose, glucose, and combinations thereof, with fructose being particularly preferred. A solid acid is preferably used as the catalyst for the dehydration reaction.

[0088] Figure 2 illustrates the process for preparing PPPS according to the present invention. The product solution obtained from the dehydration reaction of the hexahydrocarbon is first adjusted to contain a specific proportion of water. This allows for separation of two immiscible phases after extraction and assists the hydrophobic solvent in separating the humins, resulting in a more optimally separated hydrophobic and aqueous phases. This specific proportion of water can range from 0.5% to 10% by weight of the total weight of the product solution, preferably from 0.5% to 5%, and more preferably from 1% to 3%. In one embodiment, the step of adjusting the water content comprises dehydrating the product solution until the specific proportion of water is retained. Suitable dehydration treatment methods include any mild dehydration method that does not substantially disrupt the HMF molecular structure or induce chemical changes. Preferably, a water absorbent is added at a relatively low temperature, such as room temperature. Suitable water absorbents include, but are not limited to, molecular sieves, anhydrous sodium sulfate, calcium hydride, activated alumina, barium oxide, and barium sulfate.

[0089] Next, a hydrophobic solvent is mixed with the product solution obtained from the dehydration reaction of the hexahydrocarbon carbohydrate to perform extraction. The term "hydrophobic solvent" as used in the present invention refers to a solvent that is poorly soluble in water and has an n-octanol-water partition coefficient (logP) between 2.45 and 3.00. The "n-octanol-water partition coefficient" referred to herein is a value described in the paper Sangster, J., Octanol-water partition coefficients of simple organic compounds, J. Phys. Chem. Ref. Data, 18(3): 1111-1229 (1989), which represents the ratio of the solubility of a given hydrophobic solvent in n-octanol (non-polar solvent) to water (polar solvent); the higher the value, the less soluble it is in water. Preferably, the solubility of the hydrophobic solvent in water is less than 0.100% by weight. Examples of hydrophobic solvents include, but are not limited to, toluene, 1-hexyne, 1,5-hexadiene, cyclopentane, 1,3-cyclohexadiene, cyclohexene, 1,3,5-cycloheptatriene, styrene, 1-octanol, 2-octanol, 4-octanol, 2,3,6-trimethylphenol, 2,4,6-trimethylphenol, benzhydrol, 4-phenylcyclohexanone, diphenylacetic acid, ethyl benzoate, carbon tetrachloride, 1-chlorobutane, 1-fluorobutane, bromobenzene, chlorobenzene, benzyl bromide, 1-methylindole, 2-methylindole, 3-methylindole, 5-methylindole, 2-phenylpyrrole, 2-phenylpyridine, 4-phenylpyridine, N-phenylpyridine, octanonitrile, 3-nitrotoluene, and combinations thereof. In the present invention, preferred embodiments are benzene solvents, particularly toluene. The logP values ​​and solubility in water of these hydrophobic solvents are listed in Table 1 below.

[0090] Table 1. Octanol-water partition coefficient (logP) and solubility in water of hydrophobic solvents

[0091] The hydrophobic solvent and the product solution obtained from the dehydration reaction are mixed in a volume ratio of greater than or equal to 4 / 1, preferably greater than or equal to 9 / 1, and more preferably greater than or equal to 15 / 1, to achieve a satisfactory HMF recovery rate in the hydrophobic phase, as shown in Preparation Example 2 and Figure 9 below. The separation of the hydrophobic and aqueous phases can be further stabilized by allowing the mixed solution to stand in a temperature-controlled environment. The controlled temperature can be between -40°C and 60°C, preferably between -20°C and 60°C, and more preferably between -10°C and 40°C. This temperature-controlled standing step not only facilitates separation and achieves a satisfactory HMF recovery rate in the hydrophobic phase, but also ensures that the humin content in the hydrophobic phase is sufficiently low so as not to substantially hinder the HMF separation process of the present invention. If the standing temperature exceeds 80°C, HMF is more likely to polymerize, forming humins.

[0092] After extraction, the mixture separates into two immiscible layers: a hydrophobic phase and an aqueous phase. In addition to the hydrophobic solvent and HMF, the hydrophobic phase also contains an aprotic polar solvent and trace amounts of LA and FA. The aqueous phase is primarily composed of humins, giving it a dark color while the hydrophobic phase is relatively transparent, as shown in Preparation Example 2 and Figures 8A-8C below. The hydrophobic and aqueous phases are then separated. Suitable separation procedures include all conventional liquid-liquid separation processes, such as centrifugation. Because the hydrophobic and aqueous phases are essentially immiscible, they can be separated using simple separation techniques. The resulting aqueous phase is rich in humins, an undesirable byproduct, and also contains some residual HMF. This aqueous phase can be discarded directly or subjected to secondary extraction. The hydrophobic phases obtained from these extractions can be combined to increase the overall HMF recovery rate.

[0093] The hydrophobic phase collected through the above preparation process is the starting material, the "partially purified product solution" (PPPS), of the present invention. In one embodiment, the present invention relates to a modified low-temperature three-zone SMB chromatography device. The PPPS undergoes a pretreatment to remove the hydrophobic solvent, and then undergoes treatment on this modified low-temperature three-zone SMB chromatography device to separate HMF from the aprotic polar solvent. In this embodiment, the present invention also encompasses a method for separating HMF using this modified low-temperature three-zone SMB chromatography device. In another embodiment, the present invention relates to a modified low-temperature four-zone simulated moving bed (SMB) chromatography device. The PPPS undergoes direct treatment on this modified low-temperature four-zone SMB chromatography device to separate HMF, the hydrophobic solvent, and the aprotic polar solvent in a single chromatography device. In this embodiment, the present invention also encompasses a method for separating HMF using this modified low-temperature four-zone SMB chromatography device.

[0094] Improved low-temperature three-section simulated moving bed (SMB) chromatography device and method

[0095] The present invention achieves the purification of HMF by a simulated moving bed (SMB) specifically for treating the PPPS. The term "simulated moving bed" used in the present invention refers to a continuously operated adsorption chromatography device that allows the mobile phase to flow continuously in a forward direction and simulates the reverse continuous movement of the stationary phase by regularly switching the positions of the feed port and the discharge port without actually moving the stationary phase. The simulated moving bed can be filled in a single elongated tubular column provided with several feed ports and discharge ports, preferably filled in several tubular columns each having a feed port and a discharge port. In an exemplary embodiment of the present invention, the simulated moving bed is filled in eight tubular columns, but it is obvious to those with ordinary knowledge in the art that each functional section of the simulated moving bed can be provided with one or more tubular columns according to actual needs, and the total number is not limited to eight.

[0096] Figure 3 is a flow chart of a first embodiment of the present invention for separating HMF, which involves first removing the hydrophobic solvent from the PPPS, followed by a three-segment SMB chromatography step to separate HMF from the aprotic polar solvent. The method comprises: (A) removing the hydrophobic solvent from the PPPS to obtain a mixed solution containing HMF and the aprotic polar solvent; (B) providing a three-segment normal phase chromatography simulated moving bed for separating HMF from the mixed solution, wherein the first segment is configured so as not to be directly connected to the second and third segments; (C) sequentially passing a first eluent through the second and third segments at an operating temperature below 80°C, while simulating stationary phase movement in opposite directions, such that HMF migrates to the raffinate end of the third segment along with the first eluent, while the aprotic polar solvent migrates to the first segment; and (D) collecting the HMF and the first eluent from the raffinate end, and separating HMF from the first eluent.

[0097] Step (A) involves removing the hydrophobic solvent from PPPS. Applicable removal means include but are not limited to chemical separation processes such as distillation, fractionation, evaporation, extraction, adsorption, concentration, drying, crystallization, etc., which depends on the chemical properties of the hydrophobic solvent. Preferably, the hydrophobic solvent after recovery can be recycled and used as an extraction agent to extract the product solution obtained by the dehydration reaction of six-carbon carbohydrates. As shown in Example 1 below, in the specific example where the hydrophobic solvent is toluene, step (A) includes distilling, preferably vacuum distilling, and recovering toluene from the PPPS. After removing the hydrophobic solvent, the resulting mixed solution mainly comprises HMF and aprotic polar solvent.

[0098] Step (B) includes providing a modified low-temperature three-section SMB first disclosed by the present invention, which is suitable for separating HMF from the mixed liquid. An important feature of the modified low-temperature three-section SMB is that the operating temperature of the entire device is lower than 80°C, preferably lower than 60°C, and more preferably lower than 40°C. As mentioned above, HMF has the characteristics of low melting point, high boiling point, and easy miscibility with other substances, and HMF is extremely sensitive to temperature. The low-temperature operating characteristics of the present invention can overcome many problems faced when separating HMF from the solvent. Figure 4 shows a structural schematic diagram of a modified low-temperature three-section SMB chromatography device according to a specific example of the present invention. The control of the above-mentioned operating temperature can be achieved by setting a temperature control component 30 in the chromatography device, such as setting a heater and / or a cooler.

[0099] The improved low-temperature three-segment SMB chromatography device disclosed herein comprises three sections: Section 1, Section 2, and Section 3, each containing at least one chromatography column. As shown in Figure 4, the three-segment SMB is composed of eight normal-phase chromatography columns, C1-C8, in a 2 / 3 / 3 configuration. That is, Section 1, Section 2, and Section 3 comprise two, three, and three normal-phase chromatography columns, respectively. Another feature of the improved low-temperature three-segment SMB chromatography device disclosed herein is that Section 1 and Section 2 are not directly connected, unlike conventional three-segment SMB devices, where Section 1 is directly connected to Section 2. Preferably, the first section is configured to be fluidically disconnected from the second and third sections. That is, no fluid channel is provided between the first and second sections or the fluid channel is blocked, while the second and third sections are configured to be fluidically connected, so that the mobile phase in the first section cannot communicate with the mobile phases in the second and third sections. As described in detail below, this structural configuration allows the use of a different type of washing agent in the first section than in the second and third sections. This has the advantage that different types of solvents can be used in different sections to effectively separate and desorb substances with different retention properties. Therefore, compared to using a large amount of a single washing agent for washing, the device of the present invention has the advantages of saving solvent usage and reducing the operating volume of subsequent steps. As shown in FIG4 , the improved low-temperature three-zone SMB chromatography device has a second wash port D2 and a cleaning port W for feeding and discharging a second polar washing agent, respectively, upstream and downstream of the first zone. A first wash port D1 for feeding a first non-polar washing agent is provided upstream of the second zone. A raw material feed port F is provided between the second and third zones as the inlet for the mixed liquid. A raffinate port R is provided downstream of the third zone as the outlet for the separated HMF.

[0100] The term "normal phase chromatography column" herein refers to a chromatography column filled with the same polar adsorbent as the stationary phase, such that when a non-polar first eluent flows through the column, more polar substances are more readily adsorbed by the stationary phase. In a preferred embodiment, the stationary phase is a surface-modified silica adsorbent, such as bare silica gel, and the first polar eluent can be selected from ethyl acetate, n-butyl acetate, n-propanol, methyl isobutyl ketone (MIBK), tetrahydrofuran (THF), isopropanol, methyl ethyl ketone, and combinations thereof. In this embodiment, ethyl acetate is particularly preferred.

[0101] The main components of the mixed liquid are a highly polar aprotic polar solvent and HMF. HMF is also a polar molecule, but its polarity is lower than that of the aprotic polar solvent. "Polar" as used herein refers to a substance having a dielectric constant greater than or equal to 15, while "non-polar" refers to a substance having a dielectric constant less than 15. Taking two aprotic polar solvents suitable for use in the present invention as an example, DMSO has a dielectric constant of approximately 47, while DMF has a dielectric constant of approximately 38. Therefore, in this improved low-temperature three-zone SMB chromatography device, the aprotic polar solvent is more readily adsorbed by the polar stationary phase than HMF. Therefore, in this specific example, the aprotic polar solvent is a highly retentive component, while HMF is an intermediately retentive component.

[0102] In step (C), the mixed liquor is fed into the three-segment simulated moving bed through the raw material feed port F located between the second and third segments, where it comes into contact with the polar stationary phase. Simultaneously, a non-polar first wash solvent is fed into the simulated moving bed through the first wash end D1 located between the first and second segments. The first wash solvent flows sequentially through the second and third segments, while the stationary phase simulates movement in a direction opposite to that of the first wash solvent. At this point, the aprotic polar solvent is adsorbed by the stationary phase in the third segment and, following the simulated movement of the stationary phase, enters the second and first segments, respectively. HMF then moves along with the first wash solvent to the raffinate end R of the third segment.

[0103] As shown in FIG4 , the first wash end D1, the second wash end D2, and the raw material feed port F are each equipped with a flow control assembly 40, such as an HPLC liquid pump, to control the volume of the first wash solvent, the second wash solvent, and the mixed solution fed into the SMB per unit time. To effectively separate the two components, HMF and the aprotic polar solvent, in the three-segment SMB chromatography device, the relative volumetric flow rates of the mobile phase (in this example, the first wash solvent) and the stationary phase in the second and third segments are set to satisfy the following equation (1):

[0104] where m2 and m3 are the relative volume flow rates of the mobile phase and the stationary phase in the second and third segments, respectively (i.e., the volume flow rate of the mobile phase in the segment divided by the volume flow rate of the stationary phase), and K A and K B are the retention constants obtained by washing the intermediate retentive component (HMF in this case) and the strongly retentive component (aprotic polar solvent in this case) with the first stream of washing agent in a simulated moving bed, respectively. Equation (1) is defined according to the trigonometric theory proposed by Yu et al. in 2002 (see Yu, HW and Ching, CB, Optimization of a simulated moving bed based on an approximated Langmuir model. AIChE J. 48(10):2240-2246), which is incorporated herein by reference in its entirety.

[0105] In step (D), HMF that has migrated to the third section along with the first-stream wash is collected from the raffinate end R. Subsequently, HMF is separated from the first-stream wash. Applicable separation methods include, but are not limited to, chemical separation processes such as distillation, fractionation, evaporation, extraction, adsorption, concentration, drying, and crystallization, depending on the chemical properties of the first-stream wash. Preferably, the recovered first-stream wash can be recycled and reused in the simulated moving bed. In the embodiment where the first-stream wash is ethyl acetate, step (D) comprises recovering the ethyl acetate by evaporation, leaving primarily HMF. In preferred embodiments, the separation of HMF may also comprise crystallization, for example, after recovering the ethyl acetate, the HMF is crystallized at room temperature under low humidity through steps such as concentration and drying.

[0106] Step (C) also includes simultaneously washing the first section with a second polar washing agent, which comprises feeding a polar second washing agent into the simulated moving bed via a second washing end D2 located upstream of the first section, allowing the second polar washing agent to flow through the first section. This allows the second polar washing agent to compete with the aprotic polar solvent for the adsorption area of ​​the stationary phase, thereby desorbing the aprotic polar solvent and discharging the aprotic polar solvent from the washing end downstream of the first section. In a preferred embodiment, the second polar washing agent is selected from methanol, acetonitrile, acetic acid, aniline, dimethylformamide, ethylene glycol, and combinations thereof, with methanol being particularly preferred. The eluate primarily contains the aprotic polar solvent and the second polar washing agent. Following this washing step, a further step of separating the aprotic polar solvent and the second polar washing agent may be further included. Applicable separation methods include, but are not limited to, chemical separation processes such as distillation, fractionation, evaporation, extraction, adsorption, concentration, drying, and crystallization, depending on the chemical properties of the aprotic polar solvent and the second polar washing agent. Preferably, the recovered aprotic polar solvent and second polar wash solvent can be recycled. In the embodiment where the second polar wash solvent is methanol, the separation step comprises recovering the methanol by distillation, while retaining the aprotic polar solvent. The conditions for distilling the methanol can be as described in Example 3 below.

[0107] In the improved low-temperature three-zone SMB chromatography device of the present invention, the first zone is not directly connected to the second zone. Preferably, the first zone is fluidically disconnected from the second and third zones. A second wash port D2 is provided upstream of the first zone for feeding a second polar wash solvent, and a first wash port D1 is provided upstream of the second zone for feeding a first non-polar wash solvent. This prevents the second wash solvent from escaping into other zones and mixing with the first wash solvent. This structural configuration allows two solvents of significantly different polarities to be introduced separately into the first zone and the second and third zones, effectively separating HMF and the aprotic polar solvent in the second and third zones, with desorption occurring in the first and third zones, respectively. Of particular note, the inventors discovered that when using a conventional three-zone SMB device (i.e., with the first and second zones directly connected) to separate HMF and DMSO, washing the first zone with a non-polar first eluent (e.g., ethyl acetate) fails to effectively desorb DMSO, requiring significant amounts of solvent to regenerate the stationary phase. The inventors further discovered that, using the improved low-temperature three-zone SMB chromatography device of the present invention (i.e., with the first and second zones not directly connected), HMF and the aprotic polar solvent can be separated in the second and third zones using a first non-polar eluent. Subsequently, washing the first zone with a second polar eluent, such as methanol, a different polar eluent, allows for highly effective DMSO desorption, thereby saving solvent usage and reducing the operating volume of subsequent steps.

[0108] In the improved low-temperature three-zone SMB disclosed herein, a cleaning-in-place (CIP) zone can be positioned upstream of the first zone, preferably comprising a chromatography column. The CIP zone is configured to be not directly connected to the first zone, and preferably, the CIP zone and the first zone are fluidically disconnected, allowing the first non-polar detergent to flow through the CIP zone without escaping into the first zone, thereby regenerating the stationary phase. Therefore, step (C) further comprises simultaneously rinsing the CIP zone with the first non-polar detergent. This allows the column, soaked with the second polar detergent, to be rinsed with the first non-polar detergent during simulated movement from the first zone to the CIP zone before returning to the SMB system. This ensures that the second polar detergent is not carried to the third zone during the simulated movement of the stationary phase.

[0109] Improved low-temperature four-zone simulated moving bed (SMB) chromatography apparatus and method.

[0110] Figure 5 is a flow chart of a second embodiment of the present invention for separating HMF, which involves directly subjecting the PPPS to a four-segment SMB chromatography step to separate HMF, a hydrophobic solvent, and an aprotic polar solvent in a single chromatography system. The method comprises: (A) providing a four-segment simulated moving bed for separating HMF from the PPPS, wherein segment 0 is configured to be not directly connected to segments 1, 2, and 3; (B) flowing a first eluent sequentially through segments 1, 2, and 3 at an operating temperature below 80°C, while causing the stationary phases to simulate movement in opposite directions, such that HMF moves to the extraction end, while the aprotic polar solvent and the hydrophobic solvent move to segments 0 and 3, respectively; and (C) collecting HMF and the first eluent from the extraction end, and separating HMF from the first eluent.

[0111] Step (A) provides a simulated moving bed specifically for separating HMF directly from the aforementioned PPPS. Figure 6 is a schematic diagram of the structure of an improved low-temperature four-segment simulated moving bed chromatography apparatus according to one embodiment of the present invention, comprising four sections, namely, section 0, section 1, section 2, and section 3. As shown in Figure 6 , the four-segment SMB is composed of eight chromatography columns, i.e., sections 0, 1, 2, and 3 are composed of one, two, two, and two columns, respectively. Preferably, a clean-in-place (CIP) section consisting of one column is provided upstream of section 0 for regenerating the stationary phase. This four-segment SMB features a second wash port D2 and a cleaning port W upstream and downstream of segment 0, respectively, for feeding and discharging a second wash agent. A first wash port D1, for feeding a first wash agent, is located upstream of segment 1. An extraction port E is located between segments 1 and 2, serving as an outlet for separated HMF. A feed port F is located between segments 2 and 3, serving as an inlet for PPPS. A raffinate port R is located downstream of segment 3, serving as an outlet for weakly and strongly retentive components. As described below, the term "weakly retentive component" refers to a hydrophobic solvent in normal phase chromatography and an aprotic polar solvent in reversed phase chromatography. The improved low-temperature four-segment SMB chromatography device disclosed herein builds upon the previously described three-segment SMB by adding a segment 0 for desorbing strongly retentive components. By adjusting the flow rate of the mobile phase in each segment, the intermediately retentive component, HMF, is collected at the extraction port E. In this improved low-temperature four-zone SMB chromatography device, the three main components of the PPPS—HMF, a hydrophobic solvent, and an aprotic polar solvent—are separated in zones 2 and 3. The weakly retentive component and the intermediately retentive component, HMF, are separated, while the strongly retentive component is carried to zone 0, where it is desorbed by a second eluent with a strong desorption capacity. As described below, the "strongly retentive component" referred to herein is the aprotic polar solvent in normal phase chromatography and the hydrophobic solvent in reversed phase chromatography.

[0112] As shown in FIG6 , in the improved low-temperature four-segment SMB chromatography device of the present invention, segment 0 is not directly connected to segment 1. Preferably, segment 0 is fluidically disconnected from segments 1, 2, and 3, while segments 1, 2, and 3 are fluidically connected, such that the mobile phase in segment 0 cannot communicate with the mobile phases in segments 1, 2, and 3. As previously mentioned, this structural configuration allows the use of different types of eluents in segment 0 than in segments 1, 2, and 3. This allows for the use of different solvents in different segments to effectively separate and desorb substances with different retention properties.

[0113] As shown in FIG6 , the improved low-temperature four-zone SMB chromatography apparatus of the present invention is equipped with a temperature control component 30 , such as a heater and / or cooler, for controlling the operating temperature of the entire apparatus to below 80° C., preferably below 60° C., and more preferably below 40° C., to prevent undesirable chemical reactions of HMF caused by high temperatures.

[0114] As shown in Examples 6 and 7 below, the present inventors conducted preliminary tests of the four-segment SMB using a single HPLC column system and found that the four-segment SMB disclosed in the present invention could successfully separate the three main components of HMF, hydrophobic solvent, and aprotic polar solvent from each other, regardless of whether a normal phase or reverse phase chromatography column was used, thereby directly separating HMF from PPPS.

[0115] In a preferred embodiment, according to the aforementioned article by Yu et al. on trigonometric theory, in order to effectively separate the three main components of HMF, hydrophobic solvent, and aprotic polar solvent, the relative volume flow rates of the mobile phase and the stationary phase in the second and third sections of the improved low-temperature four-section SMB chromatography device of the present invention are set to satisfy the following formula (1):

[0116] Where m2 and m3 are the relative volume flow rates of the mobile phase (in this case, the first flow detergent) and the stationary phase in the second and third segments, respectively, and K A and K B The retention constants are the retention constants of the weakly retentive component (a hydrophobic solvent in the case of normal phase chromatography and an aprotic polar solvent in the case of reversed phase chromatography) and the intermediately retentive component (HMF in this example) when eluted with the first eluent in a simulated moving bed.

[0117] Preferably, in order to prevent the strongly retentive component (an aprotic polar solvent in the example of normal phase chromatography, and a hydrophobic solvent in the example of reversed phase chromatography) from being discharged at the extraction end (E) along with the intermediate retentive component (HMF in this example), the operations of the second and third sections are set to satisfy the following formula (2):

[0118] Among them, m2, m3 and K B The definition is as above, K C is the retention constant of the strongly retentive component obtained by washing with the first flow eluent in the simulated moving bed, n2 is the number of columns in the second section, and ε is the porosity in the chromatography column.

[0119] In addition, the operation of the 0th segment is also set to satisfy the following formula (3): K C o ≦m o ………(3)

[0120] where K C o Represents the Henry constant of the strongly retentive component in the 0th segment, m o Represents the relative volume flow rate of the mobile phase (the second flow detergent in this example) and the stationary phase in segment 0.

[0121] In one embodiment, the improved low-temperature four-zone SMB chromatography device is composed of several normal phase chromatography columns. The term "normal phase chromatography column" as used herein has the same definition as above. These normal phase chromatography columns are filled with a stationary phase composed of a polar adsorbent. Preferably, the stationary phase is a surface-modified silica adsorbent, such as bare silica gel. The first polar eluent can be selected from ethyl acetate, n-butyl acetate, n-propanol, methyl isobutyl ketone (MIBK), tetrahydrofuran (THF), isopropanol, methyl ethyl ketone, and combinations thereof. In this embodiment, ethyl acetate is particularly preferred. In this embodiment, substances with greater polarity are more readily adsorbed by the stationary phase composed of a polar adsorbent. Therefore, aprotic polar solvents (such as DMSO) are strongly retentive components, HMF is intermediately retentive components, and hydrophobic solvents (such as toluene) are weakly retentive components. In step (B), PPPS is fed into the four-segment simulated moving bed via the feedstock inlet F located between the second and third segments, where it comes into contact with the polar stationary phase. Simultaneously, a non-polar first wash solvent is fed into the simulated moving bed via the first wash end D1 located between segments 0 and 1. The first non-polar wash solvent flows sequentially through segments 1, 2, and 3, causing the stationary phase to simulate movement in a direction opposite to the flow of the first non-polar wash solvent. At this point, the aprotic polar solvent is adsorbed by the stationary phase in segment 3 and, following the simulated movement of the stationary phase, enters segment 0. The intermediate-retaining component, HMF, also migrates upstream to segment 1, where it is washed by the high-speed flow of the first non-polar wash solvent and discharged from the extraction end E. The hydrophobic solvent, along with the first non-polar wash solvent, migrates to segment 3 and is discharged from the raffinate end R.

[0122] In another embodiment, the improved low-temperature four-zone SMB chromatography device is composed of several reversed-phase chromatography columns. The term "reversed-phase chromatography columns" herein means that each column is filled with the same non-polar adsorbent as the stationary phase, allowing a polar first eluent to flow through the column, such that less polar substances are more readily adsorbed by the stationary phase. In a preferred embodiment, the stationary phase is a surface-modified silica adsorbent, such as octadecylsilane (C18), and the first polar eluent is a 5% methanol-water solution. In this embodiment, a hydrophobic solvent (e.g., toluene) is a strongly retentive component, HMF is an intermediately retentive component, and an aprotic polar solvent (e.g., DMSO) is a weakly retentive component. In step (B), PPPS is fed into the four-section SMB via the feedstock inlet F located between sections 2 and 3, where it comes into contact with the non-polar stationary phase. Simultaneously, a first polar detergent is fed into the simulated moving bed via the first wash end D1 located between sections 0 and 1. The first polar detergent flows sequentially through sections 1, 2, and 3, while the stationary phase simulates movement in a direction opposite to the flow of the first polar detergent. At this point, the hydrophobic solvent is adsorbed by the stationary phase in section 3 and, following the simulated movement of the stationary phase, gradually enters sections 2, 1, and finally section 0. The intermediately retentive component, HMF, also migrates upstream to section 1, where it is washed by the high-speed flow of the first polar detergent and discharged from the extraction end E. The aprotic polar solvent travels with the first polar detergent to section 3 and is discharged from the raffinate end R.

[0123] Step (B) also includes simultaneously washing the 0th section with a second flow wash, which includes feeding the second flow wash into the simulated moving bed via a second flow wash end (D2) located in the 0th section, so that the second flow wash flows through the 0th section to wash out the strongly retentive components that have moved to the 0th section. In principle, when the strongly retentive component is an aprotic polar solvent, such as DMSO, a suitable second flow wash is a polar solvent, such as methanol. When the strongly retentive component is a hydrophobic solvent, such as toluene, a suitable second flow wash is a non-polar solvent, such as ethyl acetate. However, the present inventors have found that methanol is also very suitable for removing toluene that has moved to the 0th section, as shown in Example 7. Further separation and recovery means of the second flow wash are as described above.

[0124] In step (C), HMF and the first washing stream are collected from the extraction end E. Subsequently, HMF is separated from the first washing stream. Suitable separation means are as described above.

[0125] As shown in FIG6 , in the improved low-temperature four-zone SMB chromatography device of the present invention, the clean-in-place (CIP) zone is configured to be not directly connected to zone 1. Preferably, the CIP zone is fluidically disconnected from zone 0, allowing the first wash to flow through the CIP zone without escaping into zone 0, thereby regenerating the stationary phase. Therefore, step (B) further comprises simultaneously rinsing the CIP zone with the first wash, allowing the column, soaked with the second wash, to move from zone 0 to the CIP zone, where it is rinsed with the first wash, and then returned to the SMB system. This ensures that the second wash is not carried to zone 3 during the simulated migration of the stationary phase.

[0126] The following examples are for illustrative purposes only and are not intended to limit the scope of the present invention.

[0127] Preparation of 5-hydroxymethylfurfural solution.

[0128] The product solution containing 5-hydroxymethylfurfural (HMF) used in each example was generated by dehydrating a hexose in dimethyl sulfoxide (DMSO). The dehydration reaction was catalyzed by a solid acid. In addition to HMF and DMSO, the product solution also contained levulinic acid, formic acid, water, and humins.

[0129] The product solution was subjected to a dehydration step to remove most of the water in the product solution, as described in Preparation 1.

[0130] Preparation Example 1: Dehydration of product solution.

[0131] 1.1 First, filter the product solution through a filter membrane with a pore size of 0.22 μm;

[0132] 1.2 Then The product solution and the molecular sieve can be dehydrated at a ratio of, for example, 10 mL: 3 g. The mixture is allowed to stand at room temperature for 2 hours to obtain a dehydrated product solution.

[0133] The dehydrated product solution has a dark color, and its color mainly comes from the dark humic substances.

[0134] Analytical method.

[0135] In this example, an analytical method for HMF, DMSO, and LA was established using HPLC / UV equipment. This method was used to quantitatively analyze HMF, DMSO, and LA in samples containing HMF, DMSO, and LA, including the first supernatant, first lower layer, and extract. The equipment and operating conditions are exemplified below.

[0136] HPLC column: Phenomenex 5μm C18 4.6×250mm

[0137] Wash mode and flow rate: isocratic elution, 1 mL / min.

[0138] UV wavelength: 280nm for detecting HMF, 220nm for detecting DMSO, and 266nm for detecting LA.

[0139] Injection volume: 5 μl

[0140] In this preparation example, a series of standard solutions of varying concentrations were prepared for HMF, DMSO, and LA to generate calibration curves. The HMF concentrations were 0.126, 0.314, 0.628, 0.942, and 1.26 mg / mL; the DMSO concentrations were 2.646, 6.614, 9.912, 13.23, and 19.84 mg / mL; and the LA concentrations were 1.0653, 2.6634, 5.3268, and 7.9902 g / L. As shown in Figures 7A-7C , the horizontal axis represents the injected concentration (x) and the vertical axis represents the peak area (y) of the HPLC chromatogram. A standard curve was generated, and the regression equations were: y = 28712x(HMF), y = -7.2851x 2 +335.59x (DMSO) and y=35.43x (LA).

[0141] Extraction of product solution.

[0142] As previously mentioned, toluene is used as the hydrophobic solvent in the preferred embodiment of the present invention. Because toluene has a lower specific gravity than water, the upper layer after extraction and stratification is a relatively transparent hydrophobic phase, primarily containing toluene and dissolved DMSO and HMF, and may also contain LA and FA. The lower layer is an aqueous phase, darker in color, primarily containing FA, water, and humins. In this preparation, stratification was performed using toluene / dehydrated product solution volume ratios (v / v) of 15 / 1, 9 / 1, 4 / 1, and 1 / 1. An exemplary extraction procedure is shown in Preparation 2.

[0143] Preparation Example 2.

[0144] 2.1 Toluene / dehydrated product solution were mixed at volume ratios (v / v) of 15 / 1, 9 / 1, 4 / 1, and 1 / 1, respectively, and five groups were performed for each ratio.

[0145] 2.2 After mixing, place the five groups in a constant temperature water bath at 60℃, 40℃, and 20℃, an ice bath at 0℃, a -20℃ refrigerator with an actual temperature of -22.5℃, and a -40℃ refrigerator with an actual temperature of -36.7℃ for 10 minutes respectively.

[0146] 2.3 After standing, the mixture was centrifuged at 13,000 rpm for 1 minute to separate the layers, yielding a first upper hydrophobic phase and a first lower aqueous phase. Figure 8A is a photograph taken after extraction and separation, showing the upper, relatively transparent hydrophobic phase 1 and the lower, dark aqueous phase 2.

[0147] 2.4 Separate the first upper and first lower liquid layers and record their volumes and weights. Figures 8B and 8C show photographs of the immiscible upper and lower liquid layers after separation and their respective contents in microcentrifuge tubes. Figure 8B shows the relatively transparent first upper hydrophobic phase 1, while Figure 8C shows the dark first lower aqueous phase 2.

[0148] 2.5 The first upper layer was diluted 10-fold with acetone and analyzed by HPLC. The HMF recovery rate was calculated using the following formula: HMF recovery rate = HMF content in the first upper hydrophobic phase (mg) / total HMF in the dehydrated product solution (mg)

[0149] The results are shown in Figure 9 below, where the horizontal axis represents temperature (°C) and the vertical axis represents HMF recovery (%). This experimental chart shows that for HMF recovery to be greater than 50% at different operating temperatures, the toluene / dehydration product solution volume ratio must be greater than or equal to 4 / 1. For HMF recovery to reach 70%, the volume ratio must be greater than or equal to 7 / 1. For HMF recovery to reach 90%, the volume ratio must be greater than or equal to 15 / 1. Furthermore, Figure 9 shows that, at different toluene / dehydration product solution volume ratios, the temperature and recovery ratio exhibit a similar linear relationship. The smaller the toluene / dehydration product solution volume ratio, the greater the slope (e.g., 0.2729 at 4 / 1). Conversely, the smaller the slope (e.g., 0.1386 at 15 / 1), indicating that higher toluene / dehydration product solution volume ratios result in more stable HMF recovery at different operating temperatures, ensuring resistance to ambient temperature variations during production.

[0150] In addition, although the data in Figure 9 show that the HMF recovery rate increases with increasing temperature, it has been observed that the color of the first upper layer liquid also increases with increasing temperature. This means that the content of humins in the first upper layer liquid also increases with increasing temperature. Therefore, temperature is also a controlling factor.

[0151] Example 1: Removal and recovery of hydrophobic solvent.

[0152] 3.1 Referring to Preparation Example 2, toluene and the product solution were mixed in a volume ratio of 9 / 1, allowed to stand at room temperature, and separated to yield an upper hydrophobic phase and a lower aqueous phase. The upper hydrophobic phase and the lower aqueous phase were separated. The upper hydrophobic phase is referred to herein as PPPS, whose main components are HMF, toluene, and DMSO.

[0153] 5.1 DMSO / toluene binary equilibrium data were obtained from the literature and fitted to the experimental data using the binary Margules activity coefficient model. The fitting results are shown in Figures 10A-10B, where Figure 10A shows the activity coefficient fitting result and Figure 10B shows the temperature-composition phase diagram fitting result.

[0154] 5.2 The results in Figures 10A-10B further yield the temperature-composition phase diagram in Figure 11A and the XY phase diagram in Figure 11B. Based on the predicted results shown in Figure 11B, toluene can be separated from DMSO using a vacuum distillation of 10 mmHg and a temperature below 80°C without HMF destruction.

[0155] 5.3 After the toluene is distilled off, a light yellow transparent distillate is left, which mainly contains DMSO and HMF. In the embodiment of the present invention, the distillate is light yellow transparent.

[0156] Example 2: Three-section simulated moving bed.

[0157] As shown in FIG4 , the simulated moving bed 100 may include eight chromatography columns C1 to C8, each having a diameter of, for example, 1 cm ID ×25cm L The column is a stainless steel column, but is not limited thereto. Chromatography columns C1-C2 constitute the first segment, chromatography columns C3-C5 constitute the second segment, and chromatography columns C6-C8 constitute the third segment. The stationary phase is a surface-modified silica filler, which is filled in chromatography columns C1-C8. The first and second eluents constitute the mobile phase.

[0158] As shown in Figure 4 , the first wash end D1 is located between the first and second sections. A first wash agent is injected into the wash end D1, which flows through the second and third sections to remove HMF from the raffinate end R and produce a first wash liquid. A second wash agent is injected into the wash end D2, which flows through the first section to remove DMSO from the wash end W and produce a second wash liquid. The operation is illustrated in Examples 2-1 to 2-3.

[0159] Example 2-1.

[0160] Chromatography columns C1 to C8: Zeochem Eight stainless steel columns are filled with 60, 40-63 μm silica and then attached to the SMB equipment.

[0161] First and second eluents: ethyl acetate and methanol.

[0162] Sample: The distillate obtained in Example 1 was dissolved in ethyl acetate at a volume of 100 g / L. For example, 100 g of the distillate was dissolved in ethyl acetate and the volume was adjusted to 1 L. The volume was then added at a flow rate of 1 mL / min (Q F) is injected into the simulated moving bed 100 from the feed port F.

[0163] First flow wash: at a flow rate of 3 mL / min (Q D ) Ethyl acetate is injected from the first flow washing end D1.

[0164] Second flow wash: at a flow rate of 6 mL / min (Q W ) Methanol is injected from the second flow washing end D2.

[0165] Operating temperature: below 80℃.

[0166] Under the above conditions, the operation was repeated with switching times of 5, 6, 7.5, 8.0, and 8.5 minutes, respectively. The results are shown in Figure 12 and Table 2 below. As the switching time increased, the HMF signal at the raffinate end R gradually increased, while the HMF signal at the wash end W gradually decreased. After a switching time of 7.5 minutes, the HMF signal at the wash end W was almost non-existent.

[0167] Table 2

[0168] In Table 2, the HMF purity is calculated as follows:

[0169] Among them C dried HMF is the HMF concentration (mg / mL) of the dried solution (mg / L), where the dried solution is the solution after evaporation. The HMF recovery rate (Recovery) is calculated as follows:

[0170] where Q R is the flow rate of the first washing liquid at the extraction end R, Q F is the flow rate of the extract solution at the feed end F, C F HMF is the HMF concentration of the extract solution at the feed end F, and Q F is 1 mL / min, C F HMF The HMF recovery rate was 7.25 mg / L. As shown in Table 2, HMF recovery increased with increasing switching time, but purity decreased. This is presumably due to a small amount of DMSO remaining in the first-stream wash, which was not removed during the concentration process and affected HMF purity. HMF Nos. 1-3 exhibited higher purity.

[0171] Example 2-2.

[0172] Example 2-1 was repeated, but the feed rate of the ethyl acetate solution of the raffinate was increased to 2 mL / min, injected from feed port F into the simulated moving bed 100. The switching times were 5.5, 6.5, 7.5, and 8.5 min. The results are shown in Figure 13 and Table 3 below. As the switching time increased, the HMF signal at the raffinate end R gradually increased, while the HMF signal at the wash end W gradually decreased. After a switching time of 7.5 minutes, the HMF signal at the wash end W was almost absent. However, after a switching time of 6.5 minutes, a DMSO signal appeared in the first wash stream from the raffinate end R. This indicates that the column was not effectively cleaned during the cleaning phase, resulting in a large amount of DMSO remaining in the column, affecting the separation and purification process.

[0173] Table 3

[0174] The calculation method of HMF purity and recovery rate in Table 3 is the same as that in Example 2-1, except that Q F is 2mL / min, C F HMF As shown in Table 3, the HMF recovery rate increased with the increase of the switching time. However, in terms of purity, high-purity HMF was only obtained at a switching time of 5.5 minutes (No. 6). At the remaining switching times, the purity decreased due to the large amount of residual DMSO.

[0175] Example 2-3.

[0176] Example 2-1 was repeated, but the feed rate of the ethyl acetate solution of the raffinate was reduced to 0.2 mL / min or 0.1 mL / min, respectively, by injecting it into the simulated moving bed 100 from feed port F. The raffinate feed rate was increased proportionally to 500 g / L and 1120 g / L, respectively. The switching time was 7.5 min, and the results were compared with those of Example 3. As shown in Figure 14 and Table 4 below, all three groups showed almost no HMF signal at the wash end W. However, a trace amount of DMSO signal appeared at a raffinate concentration of 1120 g / L. This indicates that under the conditions of Example 11, DMSO remained in the column, resulting in residual DMSO in the first wash stream at the raffinate end R.

[0177] Table 4

[0178] The calculation method of HMF purity and recovery rate in Table 4 is the same as that in Example 2-1, except that Q F The corresponding C F HMFAs shown in Table 4, the recovery rates of the different concentrations were not significantly different, but in terms of purity, DMSO No. 11 affected the purity of HMF.

[0179] Based on the experimental results of Examples 2-1, 2-2, and 2-3, whether reducing the feed flow rate (Example 2-2) or increasing the feed concentration (Example 2-3) in the simulated moving bed 100, there was no significant change in HMF yield, and satisfactory HMF recovery rates were achieved. Therefore, the maximum feed concentration in the simulated moving bed 100 can be set to 500 g / L to avoid the problem of small amounts of precipitation caused by increasing the feed concentration.

[0180] Example 3: Methanol recovery.

[0181] Because the main components of the second-stream wash solution are methanol and DMSO, we obtained binary equilibrium data for DMSO / methanol from the literature and fitted the experimental data using the binary Margules activity coefficient model. The fitting results are shown in Figures 15A and 15B, with Figure 15A showing the activity coefficient fitting result and Figure 15B showing the temperature-composition phase diagram fitting result.

[0182] The results of Figures 15A-15B further provide the temperature-composition phase diagram of Figure 14A and the XY phase diagram of Figure 16B. Based on the predicted results shown in Figure 16B, methanol and DMSO can be separated by atmospheric distillation.

[0183] Example 4: HMF crystallization.

[0184] The first washes No. 2, 3, 6, and 10 in Examples 2-1 to 2-3 were concentrated at 50° C. and 610 mmHg for 10 minutes to 1 hour. The concentrated first washes were light orange to light yellow solutions.

[0185] The concentrated HMF-containing sample was placed in a 50 mL centrifuge tube containing a silica gel desiccant, sealed, and placed in a -20°C refrigerator overnight to obtain orange-yellow crystals.

[0186] The temperature (Tm) at which HMF crystals completely melt is generally 31-34°C. If the crystals are impure, such as if they contain other impurities, their melting temperature may deviate from the Tm. In this example, the orange-yellow crystals were placed in a constant-temperature water bath and their melting point was measured by gradually increasing the temperature. The HMF crystals were also dissolved in a solvent and analyzed for LA content using HPLC / UV. The results are shown in Table 5 below.

[0187] Table 5

[0188] Example 5: HMF crystallization.

[0189] Take 500 μL of each HMF from Samples 2 and 3 of Example 2-1, and add 2 mL of methyl tertiary butyl ether (MTBE). After mixing thoroughly, ultrasonicate for 30 seconds and place in a -40°C freezer for crystallization. The HMF used is preferably purified HMF, such as an HMF concentrate obtained by low-temperature, reduced-pressure concentration. The HMF-containing samples from Samples 2 and 3 crystallized as a light yellow solid and a dark orange solid, respectively.

[0190] After crystallization, the MTBE was decanted and washed with ice hexane. The crystalline solid was then scooped out and stored in a desiccant.

[0191] The melting point was measured according to the above method, and the results are shown in Table 6 below.

[0192] Table 6

[0193] As shown in Table 6, the use of MTBE can increase the Tm of HMF crystallization to the range of 31-34°C, indicating that its purity has been improved.

[0194] Example 6: Four-segment SMB normal phase chromatography system.

[0195] For the chromatographic separation of HMF, DMSO, and toluene, a four-segment SMB normal phase system was tested using HPLC equipment under the following conditions:

[0196] Column: Zeochem Zeoprep 60 40-63 μm silica 4.6×250 mm

[0197] First flow eluent: ethyl acetate (EA); second flow eluent: methanol (MeOH)

[0198] Flow rate: 1 mL / min

[0199] Detector: RI (410 differential refractometer Waters)

[0200] Loading solvent: EA / MeOH (56 / 44, v / v)

[0201] Operating temperature: below 80°C

[0202] Under the above chromatography conditions, a mixed sample of toluene, DMSO, HMF, and hexane was introduced and eluted with EA or MeOH to obtain an elution profile. Figure 17 shows the elution profile of toluene, DMSO, HMF, and hexane obtained with EA as the eluent. It can be seen that under the elution of ethyl acetate, the retention order of the three components is: toluene < HMF << DMSO, where DMSO is a component with extremely strong retention and is very difficult to desorb with EA. Figure 18 shows the elution profile of toluene, DMSO, HMF, and hexane obtained with MeOH as the eluent. The inventors of the present invention found that by using methanol as the eluent, DMSO can be effectively desorbed in a normal-phase chromatography column.

[0203] Taking hexane as the non-retained component, the system t o was estimated to be 3.001 min. Based on the peak elution time of the non-retained component, the porosity of the chromatography system was 0.722. The retention constants with EA as the eluent were calculated from the peak elution times of the chromatogram, which were 0.104 for toluene, 1.029 for HMF, and infinity (∞) for DMSO. If methanol was used as the eluent instead, the retention constant of DMSO was 1.279, which is summarized in Table 7 below.

[0204] Table 7. Retention times (t d ) of each component in normal-phase chromatography (0.290 min of t

[0205] ) and retention constants

[0206] where t sw is the switching time (minutes), Q i is the liquid volume flow rate of section i (mL / min), V C is the volume of the empty column (mL), and ε = the porosity of the column.

[0207] Table 8. Exemplary four-section SMB operating conditions for separating three components by normal-phase chromatography

[0208] Using a 1×25 cm normal-phase chromatography column and performing normal-phase chromatography under the three different switching time and flow rate conditions listed in Table 8, the three components of HMF, DMSO, and toluene can be effectively separated, obtaining a separation result with a purity > 95%.

[0209] Example 7: Four-zone SMB reversed-phase chromatography system.

[0210] For the chromatographic separation of HMF, DMSO, and toluene, a four-zone SMB reversed-phase chromatography system was tested using an HPLC device under the following conditions:

[0211] Column: Phenomenex 5μm C18 4.6×250mm

[0212] First eluent: 5% methanol aqueous solution (5% MeOH)

[0213] Second eluent: methanol (MeOH)

[0214] Eluent flow rate: 1.0 mL / min

[0215] Detector (wavelength): UV 280nm for HMF; UV220nm for DMSO

[0216] Injection volume: 5 μL

[0217] Operating temperature: below 80°C

[0218] Under the above chromatographic conditions, a mixed sample of toluene, DMSO, HMF, and hexane was introduced and eluted with 5% MeOH or MeOH to obtain an elution profile. Figure 20 shows the elution profile of toluene, DMSO, HMF, and hexane with 5% MeOH as the eluent. It can be seen that under the elution of 5% MeOH, the retention order of the three components is: DMSO < HMF << toluene, where toluene is a component with extremely strong retention and is very difficult to desorb with 5% MeOH. Figure 21 shows the elution profile of toluene, DMSO, HMF, and hexane with MeOH as the eluent. The inventors of the present invention found that by using methanol as the eluent, toluene can be effectively desorbed in the reversed-phase chromatography column.

[0219] Estimate the system t o as 3.102 min. Based on the peak elution time of the non-retained component, the porosity of the chromatography system is 0.747. From the peak elution time of the chromatogram, the retention constants with 5% MeOH as the eluent can be calculated, which are 0.572 for DMSO, 12.105 for HMF, and infinity (∞) for toluene. If methanol is used as the eluent instead, the retention constant of toluene is 0.662, which is summarized in Table 9 below.

[0220] Table 9. Retention times (t d ) and retention constants of each component in reversed-phase chromatography

[0221] Based on the reversed-phase chromatography data in Table 9, and using trigonometric theory to satisfy equations (1) and (3), we calculated that 0.572 ≤ m2, m3 ≤ 12.105, and 0.662 ≤ m0. The relative volumetric flow rates for each segment i were then set using the following equations. This led to the four-segment SMB reversed-phase chromatography system shown in Figure 22 and the operating conditions shown in Table 10 below.

[0222] where t sw is the switching time (minutes), Q i is the liquid volume flow rate in section i (mL / min), V C is the empty column volume (mL), ε = the porosity of the column.

[0223] Table 10. Exemplary four-segment SMB operating conditions for three-component separation using reversed-phase chromatography

[0224] Using a 1×25 cm reversed-phase chromatography column, HMF, DMSO, and toluene can be effectively separated by reversed-phase chromatography under the three different switching time and flow rate conditions listed in Table 10.

Claims

1. A method for separating 5-hydroxymethylfurfural (HMF) from a partially purified product solution of a six-carbon (C6) carbohydrate dehydration reaction, characterized in that: The partially purified product solution comprises an aprotic polar solvent, a hydrophobic solvent and HMF, and is substantially free of humins and water, wherein the polarity of the aprotic polar solvent is substantially higher than the polarity of HMF, and the polarity of HMF is substantially higher than the polarity of the hydrophobic solvent. The method comprises the following steps: A) removing the hydrophobic solvent from the partially purified product solution to obtain a mixed solution comprising HMF and the aprotic polar solvent and substantially free of humins and water; B) providing a modified low-temperature three-section simulated moving bed, which sequentially comprises a first section, a second section and a third section, each of the sections having at least one chromatography column and filled with a stationary phase consisting of a polar adsorbent, wherein the first section is configured not to be directly connected to the second and third sections; and a second flow washing end and a cleaning end located upstream and downstream of the first section, for feeding and discharging a second polar flow washing agent, respectively; a first flow washing end located upstream of the second section, for feeding a first non-polar flow washing agent; a raw material feed port located between the second section and the third section, for feeding the partially purified product solution; and a raffinate end located downstream of the third section, as an outlet for separated HMF; C) feeding the mixed liquor into the improved low-temperature three-section simulated moving bed through the raw material feed port at an operating temperature below 80° C., while allowing the first non-polar flow detergent to flow through the second section and the third section in sequence, and allowing the stationary phase to simulate movement in a direction opposite to the flow direction of the first non-polar flow detergent, wherein the relative volume flow rates of the first non-polar flow detergent and the stationary phase in the second section and the third section are set to satisfy the following formula (1): Wherein m2 and m3 are the relative volume flow rates of the first non-polar eluent and the stationary phase in the second section and the third section, respectively, K A and K B The retention constants of HMF and the aprotic polar solvent respectively obtained by washing with the first non-polar washing agent in the simulated moving bed, such that HMF moves to the raffinate end with the first non-polar washing agent, and the aprotic polar solvent moves to the first section; and D) collecting HMF and a first non-polar wash stream from the raffinate end, and separating HMF from the first non-polar wash stream.

2. A method for separating 5-hydroxymethylfurfural (HMF) from a partially purified product solution of a six-carbon (C6) carbohydrate dehydration reaction, characterized in that: The partially purified product solution comprises an aprotic polar solvent, a hydrophobic solvent and HMF, and is substantially free of humins and water, wherein the polarity of the aprotic polar solvent is substantially higher than the polarity of HMF, and the polarity of HMF is substantially higher than the polarity of the hydrophobic solvent. The method comprises the following steps: A) providing a modified low-temperature four-section simulated moving bed, which sequentially comprises the 0th section, the 1st section, the 2nd section and the 3rd section, each of which has at least one chromatography column and is filled with a stationary phase composed of a polar adsorbent, wherein the 0th section is configured not to be directly connected to the 1st, 2nd and 3rd sections; and a second flow washing end and a cleaning end located upstream and downstream of the 0th section, respectively for feeding and discharging a second polar flow washing agent; a first flow washing end located upstream of the 1st section, for feeding a first non-polar flow washing agent; an extraction end located between the 1st section and the 2nd section, serving as an outlet for HMF after separation; a raw material feed port located between the 2nd section and the 3rd section, for feeding the partially purified product solution; and a raffinate end located downstream of the 3rd section, serving as an outlet for the hydrophobic solvent after separation; B) feeding the partially purified product solution into the improved low-temperature four-section simulated moving bed through the raw material feed port at an operating temperature below 80° C., while allowing the first non-polar flow detergent to flow through the first section, the second section and the third section in sequence, and allowing the stationary phase to simulate movement in a direction opposite to the flow direction of the first non-polar flow detergent, wherein the relative volume flow rates of the first non-polar flow detergent and the stationary phase in the second section and the third section are set to satisfy the following formula (1): Wherein m2 and m3 are the relative volume flow rates of the first non-polar eluent and the stationary phase in the second section and the third section, respectively, K A and K B are the retention constants obtained by washing the hydrophobic solvent and HMF in the simulated moving bed with the first non-polar washing agent, respectively, and the relative volume flow rates of the second polar washing agent and the stationary phase in the 0th section are set to satisfy the following formula (3): K C o ≦m o ………(3) Where K C o represents the Henry constant of the aprotic polar solvent in the 0th segment, m o represents the relative volume flow rates of the second polar eluent and the stationary phase in the 0th section, such that HMF moves to the extraction end, and the aprotic polar solvent and the hydrophobic solvent move to the 0th section and the 3rd section, respectively; and C) collecting HMF and the first non-polar eluent from the extraction end, and separating HMF from the first non-polar eluent.

3. The method according to claim 1, characterized in that The first section is fluidically disconnected from the second and third sections to allow the second polar fluid detergent to flow through the first section without escaping to the second and third sections, and the second and third sections are fluidically connected to allow the first non-polar fluid detergent to flow through the second and third sections in sequence.

4. The method according to claim 2, characterized in that The 0th section is fluidically disconnected from the 1st, 2nd and 3rd sections to allow the second polar fluid detergent to flow through the 0th section without escaping to the 1st, 2nd and 3rd sections, and the 1st, 2nd and 3rd sections are fluidically connected to allow the first non-polar fluid detergent to flow through the 1st, 2nd and 3rd sections in sequence.

5. The method according to claim 1 or 2, characterized in that: The operating temperature of step (B) is below 60°C.

6. The method according to claim 5, characterized in that The operating temperature of step (B) is below 40°C.

7. The method according to claim 1, characterized in that The step (B) includes providing a clean-in-place (CIP) section upstream of the first section, wherein the clean-in-place section is fluidically disconnected from the first section to allow the first non-polar fluid detergent to flow through the clean-in-place section but not escape into the first section, and wherein the step (C) also includes simultaneously rinsing the clean-in-place section with the first non-polar fluid detergent to regenerate the stationary phase.

8. The method according to claim 2, characterized in that The step (A) includes providing a clean-in-place (CIP) section upstream of the 0th section, wherein the CIP section is fluidically disconnected from the 0th section to allow the first non-polar fluid detergent to flow through the CIP section but not escape into the 0th section, and wherein the step (B) also includes simultaneously rinsing the CIP section with the first non-polar fluid detergent to regenerate the stationary phase.

9. The method according to claim 1, characterized in that The first section, the second section and the third section are respectively composed of two, three and three chromatography columns.

10. The method according to claim 2, characterized in that The 0th section, the 1st section, the 2nd section and the 3rd section are respectively composed of one, two, two and two chromatography columns.

11. The method according to claim 1 or 2, characterized in that: The stationary phase is a surface-modified silica adsorbent.

12. The method according to claim 1 or 2, characterized in that: The first non-polar eluent is selected from the group consisting of ethyl acetate, n-butyl acetate, n-propanol, methyl isobutyl ketone (MIBK), tetrahydrofuran (THF), isopropanol, methyl ethyl ketone, and combinations thereof.

13. The method according to claim 12, characterized in that The first non-polar eluent is ethyl acetate.

14. The method according to claim 1 or 2, characterized in that: The second polar eluent is selected from the group consisting of methanol, acetonitrile, acetic acid, aniline, dimethylformamide, ethylene glycol, and combinations thereof.

15. The method according to claim 14, characterized in that The second polar eluent is methanol.

16. The method according to claim 1 or 2, characterized in that: The aprotic polar solvent is selected from the group consisting of dimethyl sulfoxide (DMSO), dimethylacetamide (DMAC), dimethylformamide (DMF), methylpyrrolidone (NMP), and combinations thereof.

17. The method according to claim 16, characterized in that The aprotic polar solvent is selected from dimethyl sulfoxide (DMSO).

18. The method according to claim 1 or 2, characterized in that: The hydrophobic solvent is selected from benzene solvents.

19. The method according to claim 18, characterized in that The hydrophobic solvent is selected from toluene.

20. The method of claim 1, wherein: The step (A) comprises recovering the hydrophobic solvent from the partially purified product solution by vacuum distillation.

21. The method of claim 1, wherein: The step (C) further comprises simultaneously washing the first section with the second polar washing agent, wherein the washing comprises feeding the second polar washing agent through the second washing end, allowing the second polar washing agent to flow through the first section to desorb the aprotic polar solvent, and allowing the aprotic polar solvent to be discharged from the washing end.

22. The method of claim 2, wherein: The step (B) further comprises simultaneously washing the 0th section with the second polar washing agent, wherein the washing comprises feeding the second polar washing agent through the second washing end, allowing the second polar washing agent to flow through the 0th section to desorb the aprotic polar solvent, so that the aprotic polar solvent is discharged from the washing end.

23. The method of claim 1, wherein: This step (D) comprises recovering ethyl acetate by evaporation.

24. The method of claim 23, wherein: The step (D) further comprises, after recovering the ethyl acetate, crystallizing HMF at room temperature with low humidity.

25. The method of claim 2, wherein: This step (C) comprises recovering the ethyl acetate by evaporation.

26. The method of claim 25, wherein: The step (C) further comprises, after recovering the ethyl acetate, crystallizing HMF at room temperature with low humidity.

27. The method of claim 1, wherein: The step (C) further comprises setting the flow rate of the first non-polar washing agent to 3 mL / min, setting the flow rate of the second polar washing agent to 6 mL / min, setting the flow rate of the raw material feed port to 0.2-2 mL / min, and setting the switching time of the chromatography columns to 5 minutes to 8.5 minutes.

28. The method of claim 2, wherein: The step (B) further comprises: setting the relative volume flow rates m2 and m3 of the first non-polar flow wash agent and the stationary phase in the second section and the third section to 0.104≦m2 and m3≦1.029, and setting the relative volume flow rate m2 and m3 of the second polar flow wash agent and the stationary phase in the 0th section to 0.104≦m2 and m3≦1.

029. o Set to 1.279≦m o .

29. The method of claim 2, wherein: The step (B) further comprises: setting the flow rate of the first non-polar eluent to 8 mL / min, setting the flow rate of the raw material feed port to 0.4 mL / min, and setting the switching time of the chromatographic columns to 200-220 seconds.

30. A method for separating 5-hydroxymethylfurfural (HMF) from a partially purified product solution of a six-carbon (C6) carbohydrate dehydration reaction, characterized in that: The partially purified product solution comprises an aprotic polar solvent, a hydrophobic solvent and HMF, and is substantially free of humins and water, wherein the polarity of the aprotic polar solvent is substantially higher than the polarity of HMF, and the polarity of HMF is substantially higher than the polarity of the hydrophobic solvent. The method comprises the following steps: A) providing a modified low-temperature four-section simulated moving bed, which sequentially comprises the 0th section, the 1st section, the 2nd section and the 3rd section, each of which has at least one chromatography column and is filled with a stationary phase composed of a non-polar adsorbent, wherein the 0th section is configured not to be directly connected to the 1st, 2nd and 3rd sections; and a second flow washing end and a cleaning end located upstream and downstream of the 0th section, respectively for feeding and discharging a second flow washing agent; a first flow washing end located upstream of the 1st section, for feeding a first polar flow washing agent; an extraction end located between the 1st section and the 2nd section, serving as an outlet for HMF after separation; a raw material feed port located between the 2nd section and the 3rd section, for feeding the partially purified product solution; and a raffinate end located downstream of the 3rd section, serving as an outlet for the aprotic polar solvent after separation; B) feeding the partially purified product solution into the improved low-temperature four-section simulated moving bed through the raw material feed port at an operating temperature below 80° C., while allowing the first polar flow detergent to flow through the first section, the second section and the third section in sequence, and allowing the stationary phase to simulate movement in a direction opposite to the flow direction of the first polar flow detergent, wherein the relative volume flow rates of the first polar flow detergent and the stationary phase in the second section and the third section are set to satisfy the following formula (1): Wherein m2 and m3 are the relative volume flow rates of the first polar eluent and the stationary phase in the second section and the third section, respectively, K A and K B are the retention constants obtained by washing the aprotic polar solvent and HMF in the simulated moving bed with the first polar washing agent, respectively, and the relative volume flow rates of the second washing agent and the stationary phase in the 0th section are set to satisfy the following formula (3): K C o ≦m o ………(3) Where K C o represents the Henry constant of the hydrophobic solvent in the 0th segment, m o represents the relative volume flow rates of the second eluent and the stationary phase in the 0th section, such that HMF moves to the extraction end, and the hydrophobic solvent and the aprotic polar solvent move to the 0th section and the 3rd section, respectively; and C) collecting HMF and the first polar washing agent from the extraction end, and separating HMF from the first polar washing agent.

31. The method of claim 30, wherein: The 0th section is fluidically disconnected from the 1st, 2nd and 3rd sections to allow the second flow detergent to flow through the 0th section without escaping to the 1st, 2nd and 3rd sections, and the 1st, 2nd and 3rd sections are fluidically connected to allow the first polarity flow detergent to flow through the 1st, 2nd and 3rd sections in sequence.

32. The method of claim 30, wherein: The operating temperature of step (B) is below 60°C.

33. The method of claim 32, wherein: The operating temperature of step (B) is below 40°C.

34. The method of claim 30, wherein: The step (A) includes providing a clean-in-place (CIP) section upstream of the 0th section, wherein the CIP section is fluidically disconnected from the 0th section to allow the first polarity flow detergent to flow through the CIP section but not escape into the 0th section, and wherein the step (B) also includes simultaneously rinsing the CIP section with the first polarity flow detergent to regenerate the stationary phase.

35. The method of claim 30, wherein: The 0th section, the 1st section, the 2nd section and the 3rd section are respectively composed of one, two, two and two chromatography columns.

36. The method of claim 30, wherein: The stationary phase is selected from octadecylsilane (C18), and the first polar eluent is selected from 5% methanol aqueous solution.

37. The method of claim 30, wherein: The second wash solvent is methanol.

38. The method of claim 30, wherein: The aprotic polar solvent is selected from the group consisting of dimethyl sulfoxide (DMSO), dimethylacetamide (DMAC), dimethylformamide (DMF), methyl pyrrolidone (NMP), and combinations thereof.

39. The method of claim 38, wherein: The aprotic polar solvent is selected from dimethyl sulfoxide (DMSO).

40. The method of claim 30, wherein: The hydrophobic solvent is selected from benzene solvents.

41. The method of claim 40, wherein: The hydrophobic solvent is selected from toluene.

42. The method of claim 30, wherein: The step (B) further comprises washing the 0th section with the second washing agent at the same time, wherein the washing comprises feeding the second non-polar washing agent through the second washing end, allowing the second non-polar washing agent to flow through the 0th section to desorb the hydrophobic solvent, so that the hydrophobic solvent is discharged from the washing end.

43. The method of claim 30, wherein: The step (B) further comprises: setting the relative volume flow rates m2, m3 of the first polar washing agent and the stationary phase in the second section and the third section to 0.572≦m2, m3≦12.105, and setting the relative volume flow rate m2, m3 of the second non-polar washing agent and the stationary phase in the 0th section to 0.572≦m2, m3≦12.

105. o Set to 0.662≦m o .

44. The method of claim 30, wherein: The step (B) further comprises: setting the flow rate of the first polarity flow eluent to 8.0 mL / min, setting the flow rate of the raw material feed port to 2.0 mL / min, and setting the switching time of the chromatographic columns to 6-10 minutes.

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