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WO2024082156A1 - 一种利用醇水碱解体系制备三氯蔗糖粗品的方法 - Google Patents

一种利用醇水碱解体系制备三氯蔗糖粗品的方法 Download PDF

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WO2024082156A1
WO2024082156A1 PCT/CN2022/126051 CN2022126051W WO2024082156A1 WO 2024082156 A1 WO2024082156 A1 WO 2024082156A1 CN 2022126051 W CN2022126051 W CN 2022126051W WO 2024082156 A1 WO2024082156 A1 WO 2024082156A1
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Prior art keywords
sucralose
ethyl ester
acetate
water
phase
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PCT/CN2022/126051
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English (en)
French (fr)
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陈永乐
仇鑫
赵程成
黎鹏飞
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安徽金禾实业股份有限公司
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Priority to CN202280004539.7A priority Critical patent/CN116075518B/zh
Priority to PCT/CN2022/126051 priority patent/WO2024082156A1/zh
Publication of WO2024082156A1 publication Critical patent/WO2024082156A1/zh

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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
    • C07H1/00—Processes for the preparation of sugar derivatives
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
    • C07H1/00—Processes for the preparation of sugar derivatives
    • C07H1/06—Separation; Purification
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
    • C07H5/00—Compounds containing saccharide radicals in which the hetero bonds to oxygen have been replaced by the same number of hetero bonds to halogen, nitrogen, sulfur, selenium, or tellurium
    • C07H5/02—Compounds containing saccharide radicals in which the hetero bonds to oxygen have been replaced by the same number of hetero bonds to halogen, nitrogen, sulfur, selenium, or tellurium to halogen
    • Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
    • Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
    • Y02P20/00—Technologies relating to chemical industry
    • Y02P20/10—Process efficiency

Definitions

  • the invention relates to the technical field of fine chemical industry, and in particular to a method for preparing crude sucralose by utilizing an alcohol-water alkaline hydrolysis system.
  • Sucralose commonly known as sucralose
  • sucralose is a new generation of sweeteners made from sucrose, and its sweetness is 600 times that of sucrose. It is considered to be the most valuable "zero-calorie" sugar in the 21st century due to its pure taste, non-metabolism, high sweetness, no calories, good stability and high safety. It is widely used in many fields such as food, beverages, daily chemicals and medicine.
  • Chinese patent CN113004345A discloses a method for continuously synthesizing sucralose. In the presence of alkali metal hydroxide or alkali metal alkoxide, dehydrated sucralose-6-acetate and anhydrous low-carbon alcohol are used as raw materials, and sucralose is prepared by a reactive distillation tower. The conversion rate of sucralose-6-ethyl ester is 99.5-99.9%.
  • Chinese patent CN104004032A discloses a method for preparing sucralose by continuous deacetylation of sucralose-6-acetate, wherein sucralose-6-acetate is subjected to deacetylation reaction in an alcohol solvent and an alkaline catalyst (KOH, NaOH, sodium methoxide, sodium ethoxide, potassium methoxide, potassium ethoxide) and then distilled to obtain crude sucralose, and the sucralose yield is 85.1-86.8%.
  • KOH alkaline catalyst
  • Chinese patent CN112805291A discloses a method for preparing sucralose, wherein sucralose-6-ethyl ester is dissolved in methanol, calcium oxide is added to deacylate the sucralose-6-ethyl ester, and the solution is filtered to obtain a crude sucralose product solution, and the yield of sucralose is 85-93%.
  • Chinese patent CN1814609A discloses a method for improving the yield of sucralose synthesis, wherein sucrose is synthesized into sucrose-6-ethyl ester in a suitable solvent using an azo reagent as a catalyst and acetic acid as an acylating agent; then, sucrose-6-ethyl ester is synthesized by reacting with a suitable chlorination reagent in a non-protonic polar solvent using trichloroacetonitrile as a catalyst; and finally, alcoholysis of sucralose-6-ethyl ester is completed in a KOH/methanol system to synthesize sucralose, with a yield of 63.2-68%.
  • Chinese patent CN101012250A discloses a method for preparing sucralose.
  • the method uses polymer-supported organic tin as a catalyst to react sucrose with an acylating agent to generate sucrose-6-ester with high chemical purity.
  • the sucrose-6-ester is then chlorinated and hydrolyzed with alkali to obtain sucralose.
  • the alkali hydrolysis is carried out in the presence of an alkaline substance (sodium hydroxide, potassium hydroxide) and an organic solvent (methanol or ethanol).
  • the yield of the alkali hydrolysis step is 59.7-75.2%.
  • Chinese patent CN103145772A discloses a method for preparing sucralose, wherein sucralose is obtained by strong base deprotection of sucralose-6-ester, wherein the strong base deprotection agent is sodium methoxide, sodium ethoxide, magnesium methoxide or magnesium ethoxide, and the yield is 77.1-86.8%.
  • an object of the present invention is to provide a method for preparing crude sucralose by using an alcohol-water alkaline hydrolysis system.
  • the method provided by the present invention has a high yield of sucralose.
  • the present invention provides a method for preparing crude sucralose by using an alcohol-water alkaline hydrolysis system, which is characterized by comprising the following steps:
  • the crude aqueous solution of sucralose-6-acetate includes sucralose-6-acetate, sucralose diester and tetrachlorosucrose-6-acetate;
  • step (3) washing the second ethyl ester phase with water to obtain a second aqueous phase and a third ethyl ester phase; extracting the second aqueous phase with ethyl acetate to obtain a third aqueous phase and a fourth ethyl ester phase; and returning the fourth ethyl ester phase to dissolve the crude sucralose concentrate in step (2);
  • the residual amount of ethyl acetate in the syrup is less than 0.5 g/L.
  • the content of sucralose-6-acetate in the first aqueous phase is less than 0.1 g/L.
  • the concentration of methanol in the methanol-water mixed solvent is 10 to 60 wt %.
  • the pH value of the alkaline hydrolysis reaction is 12.0 to 12.5, the temperature is 0 to 20° C., and the time is 0.5 to 2 h.
  • the water content of the crude sucralose concentrate is less than 0.1 wt %.
  • the content of inorganic salt in the second ethyl ester phase is less than 100 ppm.
  • the number of water washings is 5 to 7 times; the volume ratio of the second ethyl ester phase to the water used for the single water washing is 0.1 to 0.3:1; the water phases obtained from the first and second water washings are combined as the second water phase;
  • the aqueous phase obtained from the second to seventh washings is used for washing the second ethyl ester phase in the preparation process of the next batch of crude sucralose.
  • the content of sucralose in the third aqueous phase is less than 0.5 g/L.
  • the water content of the third ethyl ester phase concentrate is less than 0.5 wt%.
  • the sugar content of the crude sucralose ethyl acetate solution is 40-60%.
  • the crystallization temperature is 40 to 60° C. and the time is 4 to 12 hours.
  • the sucralose content in the sixth ethyl ester phase is less than 0.1 g/L.
  • the present invention provides a method for preparing crude sucralose by using an alcohol-water alkaline hydrolysis system.
  • the present invention uses an alkali metal hydroxide as an alkaline hydrolysis reagent, and the alkaline hydrolysis is performed in a methanol-water system.
  • Sucralose-6-acetate, sucralose diester and tetrachlorosucrose-6-acetate are all alkaline hydrolyzed to generate corresponding sucralose and tetrachlorosucrose, and the tetrachlorosucrose is further dechlorinated to form sucralose, so that the sucralose-6-acetate and impurities (sucralose diester and tetrachlorosucrose-6-acetate) in the first aqueous solution are converted into sucralose, thereby significantly improving the raw material conversion rate and the yield of sucralose.
  • the raw material conversion rate and the yield of sucralose in the method provided by the present invention are significantly improved.
  • the present invention performs alkaline hydrolysis in a methanol-water system, which can improve the efficiency of alkaline hydrolysis, reduce the precipitation of fat-soluble impurities during the cooling alkaline hydrolysis process, and cause uneven stirring and reduced mass transfer effect, thereby providing product yield.
  • the method provided by the present invention uses multiple concentrations and multiple extractions and back extractions between ethyl acetate/water dual solvent systems for separation, so that fat-soluble impurities and water-soluble impurities reach a balance in the system, and can also avoid the occurrence of sugar caramelization during the concentration process, thereby allowing sucralose to fully crystallize in ethyl acetate and improve the yield of sucralose.
  • Inorganic salts such as sodium chloride, potassium chloride, and ammonium chloride
  • sucralose can be extracted from the system under heating or room temperature, but the amount of ethyl acetate used is large, and the high-salt wastewater remaining after extraction also needs to be evaporated and crystallized to collect inorganic salts.
  • the method provided by the present invention utilizes the property that inorganic salts (such as sodium chloride, potassium chloride, and ammonium chloride) are insoluble in ethyl acetate.
  • the sucralose alkaline hydrolyzate is directly concentrated to remove water and methanol solvent, and then ethyl acetate is added to dissolve it.
  • Sucralose, water-soluble impurities, and fat-soluble impurities will dissolve in ethyl acetate, while inorganic salts are insoluble in ethyl acetate, thereby effectively separating the inorganic salts from sucralose and reducing the subsequent treatment cost of high-salt wastewater.
  • FIG. 1 is a process flow chart of preparing crude sucralose using an alcohol-water alkaline hydrolysis system in Example 1.
  • the present invention provides a method for preparing crude sucralose by using an alcohol-water alkaline hydrolysis system, comprising the following steps:
  • the crude aqueous solution of sucralose-6-acetate includes sucralose-6-acetate, sucralose diester and tetrachlorosucrose-6-acetate;
  • step (3) washing the second ethyl ester phase with water to obtain a second aqueous phase and a third ethyl ester phase; extracting the second aqueous phase with ethyl acetate to obtain a third aqueous phase and a fourth ethyl ester phase; and returning the fourth ethyl ester phase to dissolve the crude sucralose concentrate in step (2);
  • the invention conducts ethyl acetate extraction on a crude aqueous solution of sucralose-6-acetate to obtain a first ethyl ester phase and a first aqueous phase respectively; the first ethyl ester phase is concentrated to obtain syrup; the syrup is dissolved in a methanol-water mixed solvent to obtain a sucralose-6-acetate methanol aqueous solution; the crude aqueous solution of sucralose-6-acetate comprises sucralose-6-acetate, sucralose diester and tetrachlorosucrose-6-acetate.
  • the content of sucralose-6-acetate is preferably 50-80 g/L, more preferably 50-70 g/L;
  • the mass ratio of sucralose-6-acetate, sucralose diester and tetrachlorosucrose-6-acetate in the raw material solution is preferably 1:0.06-0.15:0.05-0.15, more preferably 1:0.08-0.1:0.06-0.1;
  • the raw material solution preferably also includes NH 4 Cl and organic impurities, and the concentration of the NH 4 Cl is preferably 80-150 g/L, more preferably 85-120 g/L; the concentration of the organic impurities is preferably 30-80 g/L, more preferably 30-50 g/L.
  • the present invention has no particular limitation on the preparation method of the crude sucralose-6-acetate aqueous solution.
  • the crude sucralose-6-acetate aqueous solution of the above components can be obtained by using a preparation method for preparing crude sucrose-6-acetate using sucrose as an initial raw material, which is well known to those skilled in the art.
  • sucrose is used as a raw material
  • N,N-dimethylformamide (DMF) is a solvent
  • organic tin is a catalyst
  • acetic anhydride is used as an acylating agent to prepare a solution containing sucrose-6-acetate; then the obtained solution containing sucrose-6-acetate is sequentially chlorinated (sulfoxide chloride), neutralized with ammonia water, vacuum concentrated to dryness, and dissolved in water to obtain a crude sucralose-6-acetate aqueous solution.
  • the temperature of the ethyl acetate extraction is preferably 40-60°C, more preferably 45-55°C, and further preferably 50°C; the present invention has no special limitation on the number of ethyl acetate extractions, based on the content of sucralose-6-acetate in the aqueous phase (i.e., the first aqueous phase) obtained by ethyl acetate extraction being less than 0.1 g/L, specifically 4-8 times; the time of a single ethyl acetate extraction is preferably 10-30 min, more preferably 15-25 min; the volume ratio of the crude sucralose-6-acetate aqueous solution to the ethyl acetate used for a single ethyl acetate extraction is preferably 1:0.2-0.6, more preferably 1:0.4-0.5.
  • the ethyl ester phases obtained by ethyl acetate extraction are combined into the first ethyl ester phase, and the raffinate phase obtained by the last ethyl acetate extraction is the first aqueous phase, and the first aqueous phase is preferably subjected to high-salt wastewater treatment.
  • the present invention has no special limitation on the concentration method, and a concentration method well known to those skilled in the art can be used, such as vacuum concentration, wherein the concentration temperature is preferably 60 to 80° C., and the vacuum degree is preferably -0.1 to -0.08 MPa (gauge pressure).
  • the present invention has no special limitation on the concentration time, and the concentration can be performed until the residual amount of ethyl acetate in the syrup is less than 0.5 g/L.
  • the present invention can avoid the generation of byproducts such as acetic acid and ethanol from ethyl acetate in the subsequent alkaline hydrolysis step, thereby further improving the purity and yield of sucralose.
  • the concentration of methanol in the methanol-water mixed solvent is preferably 10-60wt%, more preferably 20-50wt%.
  • the concentration of sucralose-6-acetate in the sucralose-6-acetate methanol aqueous solution is preferably 50-100g/L, more preferably 50-80g/L.
  • the present invention mixes the sucralose-6-acetate methanol aqueous solution with an alkali metal hydroxide, performs an alkaline hydrolysis reaction, and adjusts the pH value of the obtained reaction solution to neutral to obtain a sucralose alkaline hydrolyzate; the sucralose alkaline hydrolyzate is concentrated to obtain a crude sucralose concentrate, the crude sucralose concentrate is mixed and dissolved with ethyl acetate, and solid-liquid separation is performed to obtain a second ethyl ester phase.
  • the alkali metal hydroxide preferably includes sodium hydroxide and/or potassium hydroxide; the alkali metal hydroxide is preferably used in the form of an alkali metal hydroxide aqueous solution, and the concentration of the alkali metal hydroxide aqueous solution is preferably 10-40wt%, more preferably 20-35wt%; the present invention has no special limitation on the amount of the alkali metal hydroxide, as long as the pH value during the alkaline hydrolysis reaction is 12-12.5, and the pH value is more preferably 12.1-12.4, and further preferably 12.2-12.3; the temperature of the alkaline hydrolysis reaction is preferably 0-20°C, more preferably 5-15°C, and further preferably 5-10°C; the time of the alkaline hydrolysis reaction is preferably 0.5-2h, more preferably 1-1.5h.
  • the present invention performs alkaline hydrolysis under the above conditions, sucralose diester can be hydrolyzed to generate sucralose, sucralose-6-acetate can be dechlorinated and hydrolyzed to generate sucralose, and can also avoid the generation of byproducts due to the excessively high pH value of the alkaline hydrolysis reaction or the excessively high temperature of the alkaline hydrolysis reaction; the alkaline hydrolysis is performed in a methanol-water system, which can increase the solubility of fat-soluble impurities in the aqueous system under low temperature conditions, thereby improving the alkaline hydrolysis efficiency.
  • the present invention uses alkali metal hydroxide as an alkaline hydrolysis reagent and performs alkaline hydrolysis in a methanol-water system. Compared with the traditional sodium methoxide/methanol reaction system with higher hazard, it is not necessary to use high-purity alkali sucralose-6-acetate, omits the step of purifying sucralose-6-acetate, greatly shortens the process and reduces the production cost.
  • the acid used to adjust the pH value to neutral preferably includes hydrochloric acid; the concentration of the acid is preferably 15-35wt%, more preferably 20-30wt%.
  • the present invention has no particular limitation on the amount of the acid, as long as the system can be neutralized to a pH value of 6.8-7.
  • the present invention has no special limitation on the concentration method, and a concentration method well known to those skilled in the art can be used, such as vacuum concentration; the concentration temperature is preferably 60 to 80°C, and the vacuum degree is preferably -0.1 to -0.08 MPa (gauge pressure).
  • the present invention has no special limitation on the concentration conditions, and the concentration is performed until the water content of the crude sucralose concentrate is less than 0.1wt%.
  • the present invention can avoid the generation of acetic acid, ethanol and other byproducts from ethyl acetate in the subsequent alkaline hydrolysis step by controlling the residual amount of ethyl acetate in the sucralose-6-acetate aqueous solution, thereby further improving the purity and yield of sucralose.
  • the volume ratio of the sucralose-6-acetate methanol aqueous solution to ethyl acetate is preferably 1:0.5-1, and more preferably 1:0.6-0.9.
  • the solid-liquid separation method preferably includes filtration or suction filtration, and the purpose of the solid-liquid separation is to remove alkali metal salts and ammonium chloride; the alkali metal salts preferably include sodium chloride and/or potassium chloride.
  • the content of inorganic salts in the second ethyl ester phase is preferably ⁇ 100ppm.
  • the present invention washes the second ethyl ester phase with water to obtain a second aqueous phase and a third ethyl ester phase, respectively.
  • the number of water washings is preferably 5 to 7 times;
  • the volume ratio of the second ethyl ester phase to the single water used for washing is preferably 0.1 to 0.3:1, more preferably 0.15 to 0.25:1, and further preferably 0.2:1;
  • the present invention preferably combines the aqueous phases obtained from the first to second water washings as the second aqueous phase, and the aqueous phases obtained from the second to seventh water washings are preferably used for washing the second ethyl ester phase in the next batch of crude sucralose preparation process.
  • the aqueous phase obtained from the third water washing is preferably used for washing the second ethyl ester phase in the third batch of crude sucralose preparation process.
  • the aqueous phase is used for the first water washing of the second ethyl ester phase in the next batch of crude sucralose preparation process
  • the aqueous phase obtained by the fourth water washing is used for the second water washing of the second ethyl ester phase in the next batch of crude sucralose preparation process
  • the aqueous phase obtained by the fifth water washing is used for the third water washing of the second ethyl ester phase in the next batch of crude sucrose preparation process
  • the aqueous phase obtained by the sixth water washing is used for the fourth water washing of the second ethyl ester phase in the next batch of crude sucrose preparation process
  • the aqueous phase obtained by the seventh water washing is used for the fifth water washing of the second ethyl ester phase in the next batch of crude sucralose preparation process (i.e., the
  • the second aqueous phase is preferably subjected to ethyl acetate extraction to obtain a third aqueous phase and a fourth ethyl ester phase, respectively; the fourth ethyl ester phase is recycled to step (2) to dissolve the crude sucralose concentrate; the content of sucralose in the third aqueous phase is preferably less than 0.5 g/L; the third aqueous phase is preferably subjected to wastewater treatment.
  • the sucralose remaining in the second aqueous phase enters the fourth ethyl ester phase and is recycled to step (2), which can further improve the yield of sucralose.
  • the present invention mixes the third ethyl ester phase with water and concentrates it to obtain a third ethyl ester phase concentrate; dissolves the third ethyl ester phase concentrate in ethyl acetate to obtain a crude sucralose ethyl acetate liquid; and crystallizes the crude sucralose ethyl acetate liquid to obtain crude sucralose and a fifth ethyl ester phase, respectively.
  • the volume ratio of the third ethyl ester phase to water is preferably 1:0.1-0.3, more preferably 1:0.2.
  • the present invention has no particular limitation on the concentration method, and a concentration method well known to those skilled in the art may be used, such as vacuum concentration.
  • the concentration temperature is preferably 60 to 80° C.
  • the vacuum degree is preferably -0.1 to -0.08 MPa (gauge pressure).
  • the present invention has no particular limitation on the concentration time, and the concentration may be performed until the water content of the third ethyl ester phase concentrate is less than 0.5 wt %.
  • the present invention has no particular limitation on the amount of ethyl acetate used, and the sugar content (Bx) of the crude sucralose ethyl acetate solution is 40-60%, and the sugar content is more preferably 45-55%, and further preferably 50%.
  • the crystallization temperature is preferably 40-60°C, more preferably 45-55°C, and further preferably 50°C; the crystallization time is preferably 4-12h, more preferably 5-10h, and further preferably 6-8h.
  • the present invention preferably further comprises solid-liquid separation to obtain crude sucralose and the fifth ethyl ester phase, respectively.
  • the solid-liquid separation preferably comprises filtration or suction filtration.
  • the present invention preferably further comprises: washing the fifth ethyl ester phase with water to obtain a fourth aqueous phase and a sixth ethyl ester phase respectively; the fourth aqueous phase is preferably reused in step (4) to mix with the third ethyl ester phase; the sixth ethyl ester phase is preferably concentrated to obtain recovered ethyl acetate and sugar residue respectively.
  • the present invention has no particular limitation on the water washing, and the sucralose content in the sixth ethyl ester phase is ⁇ 0.1 g/L.
  • the sugar residue is preferably treated as solid waste.
  • Water-soluble impurities and fat-soluble impurities are both produced by sucrose in a series of reaction processes, and therefore have a similar main structure to sucralose, so that water-soluble impurities, fat-soluble impurities and sucralose all have a certain degree of mutual solubility.
  • the present invention utilizes the relationship between the three, and selects water and ethyl acetate as solvents for removing water-soluble impurities and fat-soluble impurities, so that both solvents can dissolve and carry sucralose, realize the exchange of sucralose in the two solvents, and enrich sucralose in ethyl acetate, and obtain crude sucralose by crystallization therefrom.
  • HPLC high performance liquid chromatography
  • the analytical conditions of the HPLC were: Shimadzu high performance liquid chromatograph, equipped with RID-10A differential refractometer, LC-10ADVP high pressure pump, CTO-10ASVP constant temperature box; chromatographic column: Agilent XDB C18 column (250 mm ⁇ 4.6 mm, 5 ⁇ m); mobile phase: methanol-0.125 wt% potassium dihydrogen phosphate aqueous solution (4:6, v/v); column temperature: 40 ° C; mobile phase flow rate: 1.0 mL/min; wherein methanol (chromatographic grade), potassium dihydrogen phosphate (analytical grade), and water are ultrapure water.
  • the preparation method of the crude aqueous solution of sucralose-6-acetate (referred to as the first aqueous solution, the components are shown in Table 1) used in the following examples is as follows: using sucrose as a raw material, DMF as a solvent, organotin as a catalyst, and acetic anhydride as an acylating agent to prepare a solution containing sucrose-6-acetate; the sucrose-6-acetate solution is sequentially chlorinated, neutralized with ammonia water, concentrated to dryness in vacuo, and dissolved in water to obtain a crude aqueous solution of sucralose-6-acetate.
  • the crude sucralose is prepared using the process flow chart shown in FIG1 , and the specific steps are as follows:
  • sucralose-6-acetate methanol aqueous solution was cooled to 5°C, and then a 32% sodium hydroxide aqueous solution was added dropwise, and alkaline hydrolysis reaction was carried out at 5°C and pH 12.3 for 1 hour.
  • step (5) adding pure water to the fifth ethyl ester phase to wash away residual sugar until the sucralose content is 0.07 g/L, and obtaining a fourth aqueous phase and a sixth ethyl ester phase respectively.
  • the fourth aqueous phase is reused in step (4) and concentrated to dryness together with the third ethyl ester phase;
  • the sixth ethyl ester phase is vacuum concentrated to dryness to obtain recovered ethyl acetate and sugar residue respectively, and the sugar residue is treated as solid waste;
  • step (3) the first to third washings of the second ethyl ester phase were successively carried out using the aqueous phases obtained by the third to fifth washings in step (3) during the preparation of the previous batch of crude sucralose, and the fourth to fifth washings of the second ethyl ester phase were carried out using pure water; in step (4), "adding water to the third ethyl ester phase (
  • the yield is the ratio of the mass of the final sucralose obtained divided by the mass of sucralose-6-acetate completely converted into sucralose. Both sucralose diester and sucralose-6-acetate can be converted into sucralose after alkaline hydrolysis. The theoretical maximum yield in Example 1 is 116.42%.
  • sucralose and impurities are in a state of equilibrium in the ethyl ester phase, that is, the recycling is continued until the sucralose yield is above 105%.
  • the characteristics of the system adopted by the present invention are: thanks to the conversion of sucralose diester and sucralose-6-acetate, sucralose can achieve a yield of more than 110% (calculated based on the conversion of sucralose-6-acetate into sucralose); the mutual washing and recycling of the ester phase and the aqueous phase can avoid the loss of sucralose caused by the residue and wastewater to the greatest extent.
  • the yield is low because the components that can be converted into sucralose in the ethyl acetate and water circulating in the system are low.
  • the yield is calculated by converting all sucralose-6-acetate into sucralose, the yield will exceed 100%.
  • the crude aqueous solution of sucralose-6-acetate also includes other components that can be converted into sucralose (sucralose diester and tetrachlorosucrose-6-acetate).
  • the method provided by the present invention can convert sucralose diester and tetrachlorosucrose-6-acetate into sucralose, thereby significantly improving the yield of sucralose.
  • the method provided by the present invention has a significantly improved yield of sucralose.
  • the present invention uses the crude aqueous solution of sucralose-6-acetate as a raw material, and does not need to be purified, so the process is simpler.
  • the present invention separates inorganic salts from the system before performing ethyl acetate/water double solvent extraction-strip extraction, thereby reducing the difficulty of subsequent high-salt wastewater treatment.
  • the solubility of sucralose in ethyl acetate is relatively low, and the present invention introduces fat-soluble caramel impurities in the system into ethyl acetate during the fourth ethyl ester phase and the fourth aqueous phase are recycled, which can significantly increase the solubility of sucralose in ethyl acetate, and adopts extraction, water washing, and recycling methods to balance the impurities in the system, so that sucralose can be enriched and crystallized in ethyl acetate; by increasing the number of ethyl acetate/water double solvent extraction-strip extraction, it is avoided that the subsequent mother liquor containing sucralose/or washing water needs to return to the concentration step to achieve the purpose of recovery after concentration.
  • the method provided by the present invention uses alkali metal hydroxide for alkaline hydrolysis and ethyl acetate/water dual system for extraction and impurity removal, so that sucralose-6-acetate, sucralose diester and tetrachlorosucrose-6-acetate can be converted into sucralose, and sucralose can be fully enriched and crystallized in the ethyl ester phase, thereby avoiding the loss caused by the need for purification before alkaline hydrolysis of sucralose-6-acetate in the traditional process and the loss of some useful impurities, significantly improving the yield of sucralose, creating greater value, and having great industrial prospects.

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Abstract

本发明提供了一种利用醇水碱解体系制备三氯蔗糖粗品的方法，涉及精细化工技术领域。本发明以三氯蔗糖-6-乙酸酯粗品水溶液为原料，在碱金属氢氧化物和甲醇水体系中进行碱解，能够将三氯蔗糖-6-乙酸酯粗品水溶液中的三氯蔗糖-6-乙酸酯以及氯蔗糖酯类杂质(三氯蔗糖双酯和四氯蔗糖-6-乙酸酯)均转换为三氯蔗糖，从而显著提高了三氯蔗糖的收率。本发明使用多次浓缩以及乙酸乙酯/水双溶剂体系相互间的多次萃取-反萃取进行分离，使脂溶性杂质和水溶性杂质在体系中达到平衡，能避免浓缩过程中糖类焦化的现象发生，使三氯蔗糖在乙酸乙酯中充分结晶，提高三氯蔗糖收率，有效的将无机盐与三氯蔗糖分离，降低后续高盐废水的处理成本。

Description

一种利用醇水碱解体系制备三氯蔗糖粗品的方法 技术领域
本发明涉及精细化工技术领域，特别涉及一种利用醇水碱解体系制备三氯蔗糖粗品的方法。
背景技术
三氯蔗糖，俗称蔗糖素，是一种以蔗糖为原料的新一代甜味剂，其甜度是蔗糖的600倍。因其具有口感纯正、不参与代谢、甜度高、无热量、稳定性好和安全性高等特点，被认为是21世纪最具应用价值的“零卡”糖，被广泛应用于食品、饮料、日化和医药等多个领域。
目前，关于以三氯蔗糖-6-乙酸酯为原料制备三氯蔗糖的方法报道较多，主要有有机胺催化法(例如中国专利CN101260127A、CN112771060A和CN101260127A)、离子交换树脂催化法(例如中国专利CN112409419A和CN102336787A)和碱催化法，其中，碱催化法操作简单、生产成本低，应用最为广泛。
中国专利CN113004345A公开了一种连续合成三氯蔗糖的方法，在碱金属氢氧化物或碱金属醇盐存在的条件下，以脱水三氯蔗糖-6-乙酸酯与无水低碳醇为原料，采用反应精馏塔制备三氯蔗糖，三氯蔗糖-6-乙酯转化率为99.5～99.9％。
中国专利CN104004032A公开了一种三氯蔗糖-6-乙酸酯连续脱乙酰基制三氯蔗糖的方法，将三氯蔗糖-6-乙酸酯在醇溶剂和碱性催化剂(KOH、NaOH、甲醇钠、乙醇钠、甲醇钾、乙醇钾)中进行脱乙酰基反应后精馏，得到三氯蔗糖粗品，三氯蔗糖收率为85.1～86.8％。
中国专利CN112805291A公开了一种三氯蔗糖的制备方法，将三氯蔗糖-6-乙酯溶于甲醇中，加入氧化钙，使三氯蔗糖-6-乙酯发生脱酰基反应，过滤，得到三氯蔗糖粗产品溶液，三氯蔗糖的收率为85～93％。
中国专利CN1814609A公开了一种提高三氯蔗糖合成收率的方法，以偶氮类试剂催化，以醋酸为酰化剂，在适当的溶剂中将蔗糖合成为蔗糖-6-乙酯；再以三氯乙腈催化，在非质子极性溶剂中，和适当的氯化试剂反应，合成三氯蔗糖-6-乙酯；最后在KOH/甲醇体系中，完成三氯蔗糖-6- 乙酯的醇解，进而合成三氯蔗糖，收率为63.2～68％。
中国专利CN101012250A公开了一种制备三氯蔗糖的方法，本发明以聚合物负载的有机锡为催化剂，使蔗糖与酰化试剂反应生成高化学纯度的蔗糖-6-酯，然后蔗糖-6-酯再经氯化、碱水解得到三氯蔗糖，其中，碱水解在碱性物质(氢氧化钠、氢氧化钾)和有机溶剂(甲醇或乙醇)存在条件下进行，其碱水解步骤的收率为59.7～75.2％。
中国专利CN103145772A公开了一种三氯蔗糖的制备方法，将三氯蔗糖-6-酯强碱脱保护得三氯蔗糖，其中，强碱脱保护试剂为甲醇钠、乙醇钠、甲醇镁或乙醇镁，其收率为77.1～86.8％。
然而，上述以高纯度的三氯蔗糖-6-酯为原料制备三氯蔗糖的方法，普遍存在三氯蔗糖收率低的问题。
发明内容
有鉴于此，本发明的目的在于提供一种利用醇水碱解体系制备三氯蔗糖粗品的方法，本发明提供的方法三氯蔗糖收率高。
为了实现上述发明目的，本发明提供以下技术方案：
本发明提供了一种利用醇水碱解体系制备三氯蔗糖粗品的方法，其特征在于，包括以下步骤：
(1)将三氯蔗糖-6-乙酸酯粗品水溶液进行乙酸乙酯萃取，分别得到第一乙酯相和第一水相；将所述第一乙酯相进行浓缩，得到糖浆；将所述糖浆溶解于甲醇水混合溶剂中，得到三氯蔗糖-6-乙酸酯甲醇水溶液；所述三氯蔗糖-6-乙酸酯粗品水溶液中包括三氯蔗糖-6-乙酸酯、三氯蔗糖双酯和四氯蔗糖-6-乙酸酯；
(2)将所述三氯蔗糖-6-乙酸酯甲醇水溶液与碱金属氢氧化物混合，进行碱解反应，调节得到的反应液的pH值至中性，得到三氯蔗糖碱解液；将所述三氯蔗糖碱解液进行浓缩，得到三氯蔗糖粗品浓缩物，将所述三氯蔗糖粗品浓缩物与乙酸乙酯混合溶解，固液分离，得到第二乙酯相；
(3)将所述第二乙酯相进行水洗，分别得到第二水相和第三乙酯相；将所述第二水相进行乙酸乙酯萃取，分别得到第三水相和第四乙酯相；所述第四乙酯相回用于步骤(2)中用于溶解所述三氯蔗糖粗品浓缩物；
(4)将所述第三乙酯相与水混合，进行浓缩，得到第三乙酯相浓缩 物；将所述第三乙酯相浓缩物溶解于乙酸乙酯中，得到三氯蔗糖粗品乙酸乙酯液；将所述三氯蔗糖粗品乙酸乙酯液进行结晶，分别得到三氯蔗糖粗品和第五乙酯相；
(5)将所述第五乙酯相进行水洗，分别得到第四水相和第六乙酯相；所述第四水相回用于步骤(4)中与第三乙酯相混合；将所述第六乙酯相进行浓缩，分别得到回收乙酸乙酯和糖渣。
优选地，步骤(1)中，所述糖浆中乙酸乙酯的残留量＜0.5g/L。
优选地，步骤(1)中，所述第一水相中三氯蔗糖-6-乙酸酯的含量＜0.1g/L。
优选地，步骤(1)中，所述甲醇水混合溶剂中甲醇的浓度为10～60wt％。
优选地，步骤(2)中，所述碱解反应的pH值为12.0～12.5，温度为0～20℃，时间0.5～2h。
优选地，步骤(2)中，所述三氯蔗糖粗品浓缩物的水含量＜0.1wt％。
优选地，步骤(2)中，所述第二乙酯相中的无机盐的含量＜100ppm。
优选地，步骤(3)中，所述水洗的次数为5～7次；所述第二乙酯相与水洗的单次用水的体积比为0.1～0.3：1；将第1～2次水洗得到的水相合并作为第二水相；
所述第2～7次水洗得到的水相用于下一批次三氯蔗糖粗品制备过程中所述第二乙酯相的水洗。
优选地，步骤(3)中，所述第三水相中的三氯蔗糖的含量＜0.5g/L。
优选地，步骤(4)中，所述第三乙酯相浓缩物的水含量＜0.5wt％。
优选地，步骤(4)中，所述三氯蔗糖粗品乙酸乙酯液的糖度为40～60％。
优选地，步骤(4)中，所述结晶的温度为40～60℃，时间4～12h。
优选地，步骤(5)中，所述第六乙酯相中三氯蔗糖含量<0.1g/L。
本发明提供了一种利用醇水碱解体系制备三氯蔗糖粗品的方法。本发明以碱金属氢氧化物作为碱解试剂，碱解在甲醇水体系中进行，三氯蔗糖-6-乙酸酯、三氯蔗糖双酯和四氯蔗糖-6-乙酸酯均会碱解生成对应的三氯蔗糖和四氯蔗糖，四氯蔗糖继续脱氯形成三氯蔗糖，使得第一水溶液中的三氯蔗糖-6-乙酸酯以及杂质(三氯蔗糖双酯和四氯蔗糖-6-乙酸酯)均转换为三氯蔗糖，从而显著提高了原料转化率以及三氯蔗糖的收率，相对于 以高纯度三氯蔗糖-6-乙酸酯为原料进行碱解制备三氯蔗糖的方法，本发明提供的方法中原料转化率和三氯蔗糖的收率显著提高。本发明在甲醇水体系中进行碱解，可提高碱解效率，可减少脂溶性杂质在降温碱解过程中析出，导致搅拌不均、传质效果降低的现象发生，提供产物收率。本发明提供的方法，使用多次浓缩以及乙酸乙酯/水双溶剂体系相互间的多次萃取-反萃取进行分离，使脂溶性杂质和水溶性杂质在体系中达到平衡，还能够避免浓缩过程中糖类焦化的现象发生，进而使得三氯蔗糖在乙酸乙酯中充分结晶，提高三氯蔗糖收率。无机盐(如氯化钠、氯化钾、氯化铵)易溶于水，不溶于乙酸乙酯，在碱解并调节pH值至中性后所得三氯蔗糖碱解液中存在较多的无机盐，若使用乙酸乙酯，在加热或常温下可将三氯蔗糖从体系中萃取出来，但乙酸乙酯的用量较大，且萃取后剩余的高盐废水还需要通过蒸发、结晶处理以收集无机盐。而本发明提供的方法利用无机盐(如氯化钠、氯化钾、氯化铵)不溶于乙酸乙酯的特性，直接将三氯蔗糖碱解液浓缩除去水和甲醇溶剂，然后加入乙酸乙酯溶解，三氯蔗糖、水溶性杂质以及脂溶性杂质会溶于乙酸乙酯中，而无机盐不溶于乙酸乙酯，从而有效的将无机盐与三氯蔗糖分离，降低后续高盐废水的处理成本。
附图说明
图1为实施例1利用醇水碱解体系制备三氯蔗糖粗品的工艺流程图。
具体实施方式
下面结合实施例和附图对本发明进一步说明。
本发明提供了一种利用醇水碱解体系制备三氯蔗糖粗品的方法，包括以下步骤：
(1)将三氯蔗糖-6-乙酸酯粗品水溶液进行乙酸乙酯萃取，分别得到第一乙酯相和第一水相；将所述第一乙酯相进行浓缩，得到糖浆；将所述糖浆溶解于甲醇水混合溶剂中，得到三氯蔗糖-6-乙酸酯甲醇水溶液；所述三氯蔗糖-6-乙酸酯粗品水溶液中包括三氯蔗糖-6-乙酸酯、三氯蔗糖双酯和四氯蔗糖-6-乙酸酯；
(2)将所述三氯蔗糖-6-乙酸酯甲醇水溶液与碱金属氢氧化物混合，进行碱解反应，调节得到的反应液的pH值至中性，得到三氯蔗糖碱解液；将所述三氯蔗糖碱解液进行浓缩得到三氯蔗糖粗品浓缩物，将所述三氯蔗 糖粗品浓缩物与乙酸乙酯混合溶解，固液分离，得到第二乙酯相；
(3)将所述第二乙酯相进行水洗，分别得到第二水相和第三乙酯相；将所述第二水相进行乙酸乙酯萃取，分别得到第三水相和第四乙酯相；所述第四乙酯相回用于步骤(2)中用于溶解所述三氯蔗糖粗品浓缩物；
(4)将所述第三乙酯相与水混合，进行浓缩，得到第三乙酯相浓缩物；将所述第三乙酯相浓缩物溶解于乙酸乙酯中，得到三氯蔗糖粗品乙酸乙酯液；将所述三氯蔗糖粗品乙酸乙酯液进行结晶，分别得到三氯蔗糖粗品和第五乙酯相；
(5)将所述第五乙酯相进行水洗，分别得到第四水相和第六乙酯相；所述第四水相回用于步骤(4)中与第三乙酯相混合；将所述第六乙酯相进行浓缩，分别得到回收乙酸乙酯和糖渣。
在本发明中，若无特殊说明，所有的原料组分均为本领域技术人员熟知的市售商品。
本发明将三氯蔗糖-6-乙酸酯粗品水溶液进行乙酸乙酯萃取，分别得到第一乙酯相和第一水相；将所述第一乙酯相进行浓缩，得到糖浆；将所述糖浆溶解于甲醇水混合溶剂中，得到三氯蔗糖-6-乙酸酯甲醇水溶液；所述三氯蔗糖-6-乙酸酯粗品水溶液中包括三氯蔗糖-6-乙酸酯、三氯蔗糖双酯和四氯蔗糖-6-乙酸酯。
在本发明中，所述原料液中，三氯蔗糖-6-乙酸酯的含量优选为50～80g/L，更优选为50～70g/L；所述原料液中三氯蔗糖-6-乙酸酯、三氯蔗糖双酯和四氯蔗糖-6-乙酸酯的质量比优选为1：0.06～0.15：0.05～0.15，更优选为1：0.08～0.1：0.06～0.1；所述原料液中优选还包括NH 4Cl和有机杂质，所述所述NH 4Cl的浓度优选为80～150g/L，更优选为85～120g/L；所述有机杂质的浓度优选为30～80g/L，更优选为30～50g/L。
本发明对于所述三氯蔗糖-6-乙酸酯粗品水溶液的制备方法没有特殊限定，采用本领域技术人员熟知的以蔗糖为初始原料制备蔗糖-6-乙酸酯粗品的制备方法得到上述组分的三氯蔗糖-6-乙酸酯粗品水溶液即可，具体如：以蔗糖为原料，N,N-二甲基甲酰胺(DMF)为溶剂，有机锡为催化剂，以乙酸酐为酰化剂，制得含有蔗糖-6-乙酸酯的溶液；然后将所得含有蔗糖-6-乙酸酯的溶液依次进行氯化(氯化亚砜)、氨水中和、真空 浓缩至干和加水溶解，得到三氯蔗糖-6-乙酸酯粗品水溶液。
在本发明中，所述乙酸乙酯萃取的温度优选为40～60℃，更优选为45～55℃，进一步优选为50℃；本发明对于所述乙酸乙酯萃取的次数没有特殊限定，以乙酸乙酯萃取得到的水相(即第一水相)中三氯蔗糖-6-乙酸酯的含量＜0.1g/L为准，具体如4～8次；单次乙酸乙酯萃取的时间优选为10～30min，更优选为15～25min；所述三氯蔗糖-6-乙酸酯粗品水溶液与单次乙酸乙酯萃取用乙酸乙酯的体积比优选为1：0.2～0.6，更优选为1：0.4～0.5。在本发明中，在本发明中，乙酸乙酯萃取所得乙酯相合并为第一乙酯相，最后一次乙酸乙酯萃取所得萃余相为第一水相，所述第一水相优选进行高盐废水处理。
本发明对于所述浓缩的方式没有特殊限定，采用本领域技术人员熟知的浓缩方式即可，具体如真空浓缩，所述浓缩的温度优选为60～80℃，真空度优选为-0.1～-0.08MPa(表压)，本发明对于所述浓缩的时间没有特殊限定，浓缩至所述糖浆中乙酸乙酯的残留量＜0.5g/L即可。本发明通过控制如糖浆中乙酸乙酯的残留量，能够避免在后续的碱解步骤中乙酸乙酯生成乙酸、乙醇等副产物，进一步提高了三氯蔗糖的纯度和收率。
在本发明中，所述甲醇水混合溶剂中甲醇的浓度优选为10～60wt％，更优选为20～50wt％。在本发明中，所述三氯蔗糖-6-乙酸酯甲醇水溶液中三氯蔗糖-6-乙酸酯的浓度优选为50～100g/L，更优选为50～80g/L。
得到三氯蔗糖-6-乙酸酯甲醇水溶液后，本发明将所述三氯蔗糖-6-乙酸酯甲醇水溶液与碱金属氢氧化物混合，进行碱解反应，调节得到的反应液的pH值至中性，得到三氯蔗糖碱解液；将所述三氯蔗糖碱解液进行浓缩得到三氯蔗糖粗品浓缩物，将所述三氯蔗糖粗品浓缩物与乙酸乙酯混合溶解，固液分离，得到第二乙酯相。
在本发明中，所述碱金属氢氧化物优选包括氢氧化钠和/或氢氧化钾；所述碱金属氢氧化物优选以碱金属氢氧化物水溶液形式使用，所述碱金属氢氧化物水溶液的浓度优选为10～40wt％，更优选为20～35wt％；本发明对于所述碱金属氢氧化物的用量没有特殊限定，能够将保证碱解反应过程中pH值为12～12.5即可，所述pH值更优选为12.1～12.4，进一步优选为12.2～12.3；所述碱解反应的温度优选为0～20℃，更优选为5～15℃，进一 步优选为5～10℃；所述碱解反应的时间优选为0.5～2h，更优选为1～1.5h。本发明在上述条件下进行碱解反应，三氯蔗糖双酯能够发生水解生成三氯蔗糖，四氯蔗糖-6-乙酸酯能够发生脱氯以及水解反应生成三氯蔗糖，且还能够避免因碱解反应的pH值过高或碱解反应的温度过高而产生副产物；碱解在甲醇水体系中进行，可以增加脂溶性杂质在低温条件下，在含水体系中的溶解度，从而提高碱解效率。而且，本发明以碱金属氢氧化物作为碱解试剂，在甲醇水体系中进行碱解，与传统的具有较高危害性的甲醇钠/甲醇反应体系相比，无需采用高纯度的碱三氯蔗糖-6-乙酸酯，省略了三氯蔗糖-6-乙酸酯的提纯的步骤，大大缩短流程并降低了生产成本。
在本发明中，所述调节pH值至中性采用的酸优选包括盐酸；所述酸的浓度优选为15～35wt％，更优选为20～30wt％。本发明对于所述酸的用量没有特殊限定，能够将体系中和至pH值为6.8～7即可。
本发明对于所述浓缩的方式没有特殊限定，采用本领域技术人员熟知的浓缩方式即可，具体如真空浓缩；所述浓缩的温度优选为60～80℃，真空度优选为-0.1～-0.08MPa(表压)，本发明对于所述浓缩的条件没有特殊限定，浓缩至所述三氯蔗糖粗品浓缩物的水含量＜0.1wt％即可。本发明通过控制三氯蔗糖-6-乙酸酯水溶液中乙酸乙酯的残留量，能够避免在后续的碱解步骤中乙酸乙酯生成乙酸、乙醇等副产物，进一步提高了三氯蔗糖的纯度和收率。
在本发明中，所述三氯蔗糖-6-乙酸酯甲醇水溶液与乙酸乙酯的体积比优选为1：0.5～1，更优选为1：0.6～0.9。
在本发明中，所述固液分离的方式优选包括过滤或抽滤，所述固液分离的目的除去碱金属盐以及氯化铵；所述碱金属盐优选包括氯化钠和/或氯化钾。在本发明中，所述第二乙酯相中的无机盐的含量优选＜100ppm。
得到第二乙酯相后，本发明将所述第二乙酯相进行水洗，分别得到第二水相和第三乙酯相。在本发明中，所述水洗的次数优选为5～7次；所述第二乙酯相与水洗的单次用水的体积比优选为0.1～0.3：1，更优选为0.15～0.25：1，进一步优选为0.2:1；本发明优选将第1～2次水洗得到的水相合并作为第二水相，第2～7次水洗得到的水相优选用于下一批次三氯蔗糖粗品制备过程中所述第二乙酯相的水洗，具体的，第3次水洗得到的 水相用于下一批次三氯蔗糖粗品制备过程中第二乙酯相的第1次水洗，第4次水洗得到的水相用于下一批次三氯蔗糖粗品制备过程中第二乙酯相的第2次水洗，第5次水洗得到的水相用于下一批次蔗糖粗品制备过程中第二乙酯相的第3次水洗，第6次水洗得到的水相用于下一批次蔗糖粗品制备过程中第二乙酯相的第4次水洗，第7次水洗得到的水相用于下一批次第二乙酯相的第5次水洗(即第3～7次水洗得到的水相依次用于下一批次三氯蔗糖粗品制备过程中第二乙酯相的第1～5次水洗)，下一批次三氯蔗糖粗品制备过程中第二乙酯相的第6～7次水洗优选利用纯水进行。
本发明优选将所述第二水相进行乙酸乙酯萃取，分别得到第三水相和第四乙酯相；所述第四乙酯相回用于步骤(2)中用于溶解所述三氯蔗糖粗品浓缩物；所述第三水相中的三氯蔗糖的含量优选＜0.5g/L；所述第三水相优选进行废水处理。在本发明中，第二水相中残留的三氯蔗糖进入到第四乙酯相中回用到步骤(2)中，能够进一步提高三氯蔗糖的收率。
得到第三乙酯相后，本发明将所述第三乙酯相与水混合，进行浓缩，得到第三乙酯相浓缩物；将所述第三乙酯相浓缩物溶解于乙酸乙酯中，得到三氯蔗糖粗品乙酸乙酯液；将所述三氯蔗糖粗品乙酸乙酯液进行结晶，分别得到三氯蔗糖粗品和第五乙酯相。
在本发明中，所述第三乙酯相与水的体积比优选为1：0.1～0.3，更优选为1：0.2。
本发明对于所述浓缩的方式没有特殊限定，采用本领域技术人员熟知的浓缩方式即可，具体如真空浓缩，所述浓缩的温度优选为60～80℃，真空度优选为-0.1～-0.08MPa(表压)，本发明对于所述浓缩的时间没有特殊限定，浓缩至所述第三乙酯相浓缩物的水含量＜0.5wt％即可。
本发明对于所述乙酸乙酯的用量没有特殊限定，以所述三氯蔗糖粗品乙酸乙酯液的糖度(Bx)为40～60％为准，所述糖度更优选为45～55％，进一步优选为50％。
在本发明中，所述结晶的温度优选为40～60℃，更优选为45～55℃，进一步优选为50℃；所述结晶的时间优选为4～12h，更优选为5～10h，进一步优选为6～8h。
完成所述结晶后，本发明优选还包括固液分离，分别得到三氯蔗糖粗 品和第五乙酯相。在本发明中，所述固液分离优选包括过滤或抽滤。
得到第五乙酯相后，本发明优选还包括；将所述第五乙酯相进行水洗，分别得到第四水相和第六乙酯相；所述第四水相优选回用于步骤(4)中与第三乙酯相混合；所述第六乙酯相优选进行浓缩，分别得到回收乙酸乙酯和糖渣。本发明对于所述水洗没有特殊限定，以所述第六乙酯相中三氯蔗糖含量<0.1g/L为准。在本发明中，所述糖渣优选进行固废处理。
水溶性杂质和脂溶性杂质均为蔗糖在一系列反应过程中产生的，因此与三氯蔗糖有类似的主体结构，从而使水溶性杂质、脂溶性杂质和三氯蔗糖之间均有一定的互溶度。本发明正是利用三者之间的关系，通过选用水和乙酸乙酯作为除去水溶性杂质和脂溶性杂质的溶剂，从而利用两种溶剂均可以溶解、夹带三氯蔗糖，实现三氯蔗糖在两种溶剂中的交换，并使三氯蔗糖在乙酸乙酯中富集，并从中结晶获得三氯蔗糖粗品。
下面将结合本发明中的实施例，对本发明中的技术方案进行清楚、完整地描述。显然，所描述的实施例仅仅是本发明一部分实施例，而不是全部的实施例。基于本发明中的实施例，本领域普通技术人员在没有做出创造性劳动前提下所获得的所有其他实施例，都属于本发明保护的范围。
以下各实施例中各物质的含量均采用高效液相色谱(High Performance Liquid Chromatography，HPLC)方法在下述条件下采用外标法测得，高效液相色谱的分析测定条件：日本岛津高效液相色谱仪，配RID-10A示差折光检测，LC-10ADVP高压泵，CTO-10ASVP恒温箱；色谱柱：AgilentXDB C18柱(250mm×4.6mm，5μm)；流动相：甲醇-0.125wt％磷酸氢二钾水溶液(4:6，v/v)；柱温：40℃；流动相流量：1.0mL/min；其中，甲醇(色谱纯)、磷酸氢二钾(分析纯)、水为超纯水。
以下实施例中使用的三氯蔗糖-6-乙酸酯粗品水溶液(记为第一水溶液，成分如表1所示)的制备方法如下：使用蔗糖为原料，DMF为溶剂，有机锡为催化剂，乙酸酐为酰化剂，制得含有蔗糖-6-乙酸酯的溶液；将所述蔗糖-6-乙酸酯溶液依次进行氯化、氨水中和、真空浓缩至干、加水溶解，得到三氯蔗糖-6-乙酸酯粗品水溶液。
表1 第一水溶液的成分
组分 含量
三氯蔗糖-6-乙酸酯 58.7g/L
三氯蔗糖双酯 5.6g/L
四氯蔗糖-6-乙酸酯 4.3g/L
NH 4Cl 86.6g/L
其他有机杂质 30.1g/L
水 82.4wt％
实施例1
采用图1所示的工艺流程图制备三氯蔗糖粗品，具体步骤如下：
(1)将所述第一水溶液1000mL加热至50℃，用乙酸乙酯(单次用量500mL)反复萃取4次，萃取完成后，酯相合并作为第一乙酯相，水相合并作为第一水相；所述第一水相中三氯蔗糖-6-乙酸酯含量为0.08g/L，所述第一水相进行高盐废水处理；将所述第一乙酯相真空浓缩至干(简写为浓干)，在所得糖浆(乙酸乙酯含量＜0.1g/L)中加入50wt％甲醇水混合溶剂溶解，得到1000mL三氯蔗糖-6-乙酸酯甲醇水溶液。
(2)将三氯蔗糖-6-乙酸酯甲醇水溶液降温至5℃，然后滴加浓度为32％的氢氧化钠水溶液，在5℃、pH值为12.3条件下碱解反应1h，反应结束时三氯蔗糖-6-乙酯含量为0.4g/L；然后滴加浓度为30wt％的稀盐酸中和至pH＝7，将所得三氯蔗糖碱解液浓干，在所得三氯蔗糖粗品浓缩物(水含量为0.08wt％)中加入乙酸乙酯(三氯蔗糖-6-乙酸酯甲醇水溶液与乙酸乙酯的体积比＝1：0.6)溶解，过滤，得到第二乙酯相，第二乙酯相氯化钠残余量为97ppm。
(3)将所述第二乙酯相水洗5次(第二乙酯相与水洗的单次用水的体积比＝1:0.15)，其中，第1～2次水洗得到的水相合并为第二水相，全部酯相合并为第三乙酯相；第3～5次水洗得到的水相依次用于下一批次三氯蔗糖粗品制备过程中第二乙酯相的第1～3次水洗。向第二水相中加入2倍体积的乙酸乙酯萃取，分层，分别得到第三水相和第四乙酯相；第三水相中三氯蔗糖含量为0.3g/L，第三水相进行废水处理；第四乙酯相回 用于步骤(2)中用于溶解三氯蔗糖粗品浓缩物；
(4)向所述第三乙酯相中加入水(第三乙酯相与水的体积比＝1：0.2)浓干以除去水与乙酸乙酯，在所得第三乙酯相浓缩物(水含量为0.4wt％)中加入乙酸乙酯将糖度Bx调至55％，然后在45℃条件下结晶10h，抽滤，分别得到三氯蔗糖粗品和第五乙酯相；
(5)向所述第五乙酯相中加入纯水将残糖洗净至三氯蔗糖含量为0.07g/L，分别得到第四水相和第六乙酯相。第四水相回用于步骤(4)中与第三乙酯相共同浓干；第六乙酯相真空浓缩至干，分别得到回收乙酸乙酯和糖渣，所述糖渣进行固废处理；
(6)按照步骤(1)～(5)的操作(记为循环利用0次)，将所述第四乙酯相、第四水相、第五水相(用于第二乙酯相的水洗)循环利用17次，其中，将步骤(2)中的“加入乙酸乙酯(三氯蔗糖-6-乙酸酯甲醇水溶液与乙酸乙酯的体积比＝1：0.6)溶解”替换为“加入实施例1步骤(4)所得第四乙酯相溶解”；步骤(3)中，第二乙酯相的第1～3次水洗依次利用前一批次三氯蔗糖粗品制备过程中步骤(3)中第3～5次水洗得到的水相，第二乙酯相的第4～5次水洗利用纯水进行；将步骤(4)中的“向所述第三乙酯相中加入水(第三乙酯相与水的体积比＝1：0.2)”替换为“向所述第三乙酯相中加入水实施例1步骤(5)得到的第四水相”；
得到的三氯蔗糖粗品的纯度及收率数据如表2所示。
表2 三氯蔗糖粗品纯度及收率
Figure PCTCN2022126051-appb-000001
Figure PCTCN2022126051-appb-000002
注：收率是按照最终获得的三氯蔗糖的质量除以三氯蔗糖-6-乙酸酯完全转化成三氯蔗糖的质量所占比例。三氯蔗糖双酯和四氯蔗糖-6-乙酸酯碱解后均可转化为三氯蔗糖，实施例1中理论最大收率为116.42％。
在循环套用的过程中三氯蔗糖和杂质在乙酯相中处于一种平衡状态，即循环套用至三氯蔗糖收率在105％以上，本发明采用的体系的特点是：得益于三氯蔗糖双酯和四氯蔗糖-6-乙酸酯的转化，三氯蔗糖可实现110％以上的收率(以三氯蔗糖-6-乙酸酯转化成三氯蔗糖计)；酯相与水相的相互洗涤以及套用，可最大程度的避免三氯蔗糖在糖渣和废水中残留造成的损失。
从以上实施例可以发现，在初始的几个操作流程中，例如第1～4循环套用的过程中，由于在体系中循环的乙酸乙酯和水中含有的可转化为三氯蔗糖的成分较低，因此收率较低。循环套用3次以后，如以三氯蔗糖-6-乙酸酯全部转化为三氯蔗糖作为收率计算方式，收率将超过100％，其原因是三氯蔗糖-6-乙酸酯粗品水溶液中还包括了可以转换为三氯蔗糖的其他成分(三氯蔗糖双酯和四氯蔗糖-6-乙酸酯)，本发明提供的方法能够将三氯蔗糖双酯和四氯蔗糖-6-乙酸酯转换为三氯蔗糖，从而显著提高了三氯蔗糖的收率，相对于以高纯度三氯蔗糖-6-乙酸酯为原料进行碱解制备三氯蔗糖的方法，本发明提供的方法三氯蔗糖的收率显著提高，且本发明以三氯蔗糖-6-乙酸酯粗品水溶液为原料，无需对其进行提纯，工艺更加简单。
而且，本发明在进行乙酸乙酯/水双溶剂萃取-反萃取前，将无机盐与体系分离，降低了后续高盐废水的处理难度。三氯蔗糖在乙酸乙酯中的溶解度较低，而本发明在将第四乙酯相和第四水相循环套用过程中将体系中的脂溶性焦糖类杂质引入乙酸乙酯中，可显著增加三氯蔗糖在乙酸乙酯中的溶解度，并采用萃取、水洗、循环套用的方式使体系中的杂质达到平衡，可让三氯蔗糖在乙酸乙酯中富集并结晶；通过增加乙酸乙酯/水双溶剂萃取-反萃取的次数，避免了后续含三氯蔗糖的部分母液/或水洗水需要返回浓缩步骤经过浓缩方能实现回收的目的。此外，在结晶母液(三氯蔗糖粗品乙酸乙酯液)中，由于是乙酸乙酯溶剂体系，脂溶性杂质较多，三氯蔗糖在水中的溶解度较高，因此采用多次水洗的方式可将未结晶的三氯蔗糖回收套用，脂溶性杂质排除。通过以上手段的实施，即可显著提高三氯蔗糖的收率。因此，相对于以高纯度三氯蔗糖-6-乙酸酯为原料进行碱解制备三氯蔗糖的方法，本发明提供的方法具有极为明显的优势。
综上所述，本发明提供的方法采用碱金属氢氧化物进行碱解，乙酸乙酯/水双体系套用萃取除杂，可将三氯蔗糖-6-乙酸酯、三氯蔗糖双酯和四氯蔗糖-6-乙酸酯都转化为三氯蔗糖，并在乙酯相中充分富集以及结晶三氯蔗糖，避免了传统工艺三氯蔗糖-6-乙酸酯碱解前需要提纯所造成的损耗，以及一些有用杂质的流失，显著提高了三氯蔗糖收率，创造更大价值，具有极大的工业化前景。
以上实施例的说明只是用于帮助理解本发明的方法及其核心思想。应当指出，对于本技术领域的普通技术人员来说，在不脱离本发明原理的前提下，还可以对本发明进行若干改进和修饰，这些改进和修饰也落入本发明权利要求的保护范围内。对这些实施例的多种修改对本领域的专业技术人员来说是显而易见的，本文中所定义的一般原理可以在不脱离本发明的精神或范围的情况下在其它实施例中实现。因此，本发明将不会被限制于本文所示的这些实施例，而是要符合与本文所公开的原理和新颖特点相一致的最宽的范围。

Claims (13)

  1. 一种利用醇水碱解体系制备三氯蔗糖粗品的方法，其特征在于，包括以下步骤：
    (1)将三氯蔗糖-6-乙酸酯粗品水溶液进行乙酸乙酯萃取，分别得到第一乙酯相和第一水相；将所述第一乙酯相进行浓缩，得到糖浆；将所述糖浆溶解于甲醇水混合溶剂中，得到三氯蔗糖-6-乙酸酯甲醇水溶液；所述三氯蔗糖-6-乙酸酯粗品水溶液中包括三氯蔗糖-6-乙酸酯、三氯蔗糖双酯和四氯蔗糖-6-乙酸酯；
    (2)将所述三氯蔗糖-6-乙酸酯甲醇水溶液与碱金属氢氧化物混合，进行碱解反应，调节得到的反应液的pH值至中性，得到三氯蔗糖碱解液；将所述三氯蔗糖碱解液进行浓缩，得到三氯蔗糖粗品浓缩物，将所述三氯蔗糖粗品浓缩物与乙酸乙酯混合溶解，固液分离，得到第二乙酯相；
    (3)将所述第二乙酯相进行水洗，分别得到第二水相和第三乙酯相；将所述第二水相进行乙酸乙酯萃取，分别得到第三水相和第四乙酯相；所述第四乙酯相回用于步骤(2)中用于溶解所述三氯蔗糖粗品浓缩物；
    (4)将所述第三乙酯相与水混合，进行浓缩，得到第三乙酯相浓缩物；将所述第三乙酯相浓缩物溶解于乙酸乙酯中，得到三氯蔗糖粗品乙酸乙酯液；将所述三氯蔗糖粗品乙酸乙酯液进行结晶，分别得到三氯蔗糖粗品和第五乙酯相；
    (5)将所述第五乙酯相进行水洗，分别得到第四水相和第六乙酯相；所述第四水相回用于步骤(4)中与第三乙酯相混合；将所述第六乙酯相进行浓缩，分别得到回收乙酸乙酯和糖渣。
  2. 根据权利要求1所述的方法，其特征在于，步骤(1)中，所述糖浆中乙酸乙酯的残留量＜0.5g/L。
  3. 根据权利要求1所述的方法，其特征在于，步骤(1)中，所述第一水相中三氯蔗糖-6-乙酸酯的含量＜0.1g/L。
  4. 根据权利要求1所述的方法，其特征在于，步骤(1)中，所述甲醇水混合溶剂中甲醇的浓度为10～60wt％。
  5. 根据权利要求1所述的方法，其特征在于，步骤(2)中，所述碱解反应的pH值为12.0～12.5，温度为0～20℃，时间0.5～2h。
  6. 根据权利要求1或5所述的方法，其特征在于，步骤(2)中，所述三氯蔗糖粗品浓缩物的水含量＜0.1wt％。
  7. 根据权利要求1或5所述的方法，其特征在于，步骤(2)中，所述第二乙酯相中的无机盐的含量＜100ppm。
  8. 根据权利要求1所述的方法，其特征在于，步骤(3)中，所述水洗的次数为5～7次；所述第二乙酯相与水洗的单次用水的体积比为0.1～0.3：1；将第1～2次水洗得到的水相合并作为第二水相；
    所述第2～7次水洗得到的水相用于下一批次三氯蔗糖粗品制备过程中所述第二乙酯相的水洗。
  9. 根据权利要求1或8所述的方法，其特征在于，步骤(3)中，所述第三水相中的三氯蔗糖的含量＜0.5g/L。
  10. 根据权利要求1所述的方法，其特征在于，步骤(4)中，所述第三乙酯相浓缩物的水含量＜0.5wt％。
  11. 根据权利要求1或10所述的方法，其特征在于，步骤(4)中，所述三氯蔗糖粗品乙酸乙酯液的糖度为40～60％。
  12. 根据权利要求1所述的方法，其特征在于，步骤(4)中，所述结晶的温度为40～60℃，时间4～12h。
  13. 根据权利要求1所述的方法，其特征在于，步骤(5)中，所述第六乙酯相中三氯蔗糖含量<0.1g/L。
PCT/CN2022/126051 2022-10-19 2022-10-19 一种利用醇水碱解体系制备三氯蔗糖粗品的方法 WO2024082156A1 (zh)

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