WO2024082177A1 - 一种利用水解体系制备三氯蔗糖粗品的方法 - Google Patents

一种利用水解体系制备三氯蔗糖粗品的方法 Download PDF

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WO2024082177A1
WO2024082177A1 PCT/CN2022/126186 CN2022126186W WO2024082177A1 WO 2024082177 A1 WO2024082177 A1 WO 2024082177A1 CN 2022126186 W CN2022126186 W CN 2022126186W WO 2024082177 A1 WO2024082177 A1 WO 2024082177A1
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sucralose
ethyl ester
phase
acetate
ethyl acetate
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PCT/CN2022/126186
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English (en)
French (fr)
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陈永乐
沈东东
郭思雨
肖士东
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安徽金禾实业股份有限公司
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Priority to PCT/CN2022/126186 priority Critical patent/WO2024082177A1/zh
Priority to CN202280004529.3A priority patent/CN115956082A/zh
Publication of WO2024082177A1 publication Critical patent/WO2024082177A1/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
    • C07H5/00—Compounds containing saccharide radicals in which the hetero bonds to oxygen have been replaced by the same number of hetero bonds to halogen, nitrogen, sulfur, selenium, or tellurium
    • C07H5/02—Compounds containing saccharide radicals in which the hetero bonds to oxygen have been replaced by the same number of hetero bonds to halogen, nitrogen, sulfur, selenium, or tellurium to halogen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

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  • the present invention relates to the technical field of fine chemicals, and in particular to a method for preparing crude sucralose by utilizing a hydrolysis system.
  • Sucralose commonly known as sucralose, appears as white crystalline powder or granules. It is a new generation of sweetener made from sucrose. Its sweetness is 600 times that of sucrose, with a pure taste and does not participate in human metabolism. It is a "zero-calorie" sugar that can be used by diabetics, patients with cardiovascular and cerebrovascular diseases, and the elderly. It also has the characteristics of good stability and high safety, and is widely used in food, beverages, daily chemicals, medicine and other fields.
  • the production process of sucralose mainly includes the following five steps: (1) esterification reaction: using sucrose as raw material, N,N-dimethylformamide (DMF) as solvent, organotin as catalyst, and acetic anhydride as acylating agent to carry out esterification reaction, and the reaction product is sucrose-6-ethyl ester; (2) chlorination reaction: using sucrose-6-ethyl ester as raw material, DMF and trichloroethane as solvent, and Wei's reagent or phosgene as chlorinating agent to carry out chlorination reaction, and the reaction product is sucralose-6-acetate; (3) purification of sucralose-6-acetate: using liquid The chlorinated liquid obtained by the chlorination reaction is neutralized with alkali or ammonia water, and then the solvent DMF and trichloroethane are recovered by evaporation, and then water is added to dissolve, and then pure sucralose-6-acetate is obtained through multi-stage separation and pur
  • sucralose-6-acetate As raw material, high-purity (99% or more) sucralose-6-acetate must be used and carried out under anhydrous conditions. This is because too much impurities will seriously affect the subsequent purification of sucralose, and the presence of water will affect the transesterification reaction of sucralose-6-ethyl ester, causing sucralose-6-ethyl ester to hydrolyze and generate acetic acid, affecting the quality of subsequent sucralose and reducing the yield.
  • Chinese patent CN113717237A discloses that a neutralized solution containing sucralose-6-acetate is used as a raw material, ethyl acetate extraction is performed, the obtained ester phase containing sucralose-6-acetate is subjected to ozone oxidation to remove some impurities, and then alkaline hydrolysis is performed using a sodium hydroxide/water system, and then purification is performed to obtain sucralose.
  • the patent uses a neutralized solution containing sucralose-6-acetate as a raw material, and its molar yield is 103.7-105.1%, ozone oxidation is required, which will have adverse effects on the environment and human body.
  • an object of the present invention is to provide a method for preparing crude sucralose using a hydrolysis system.
  • the method provided by the present invention has a high sucralose yield and is safe and environmentally friendly.
  • the present invention provides a method for preparing crude sucralose by using a hydrolysis system, comprising the following steps:
  • the raw material liquid is an aqueous solution including sucralose-6-acetate, sucralose diester and tetrachlorosucrose-6-acetate;
  • step (2) washing the second ethyl ester phase with water to obtain a fourth aqueous phase and a third ethyl ester phase, respectively; the fourth aqueous phase is reused in step (2) to dissolve the first ethyl ester phase concentrate;
  • the temperature of the ethyl acetate extraction is 40-60° C., and the number of extractions is 5-8 times; and the volume ratio of the raw material liquid to the ethyl acetate used for a single ethyl acetate extraction is 1:0.2-0.4.
  • the content of sucralose-6-acetate in the first aqueous phase is less than 0.1 g/L.
  • the content of ethyl acetate in the sucralose-6-acetate aqueous solution is less than 0.5 g/L.
  • the pH value of the alkaline hydrolysis reaction is 11 to 13, the temperature is 0 to 10° C., and the time is 3 to 6 hours.
  • the temperature of the hot filtration is 45-70°C.
  • the number of ethyl acetate extractions is 4 to 7 times; the volume ratio of the second aqueous phase to the ethyl acetate used in a single ethyl acetate extraction is 1:1 to 3;
  • the ethyl ester phases obtained from the first and second ethyl ester extractions are combined as the second ethyl ester phase;
  • the ethyl ester phase obtained from the 3rd to 7th ethyl acetate extractions is used for the ethyl acetate extraction of the second aqueous 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 number of water washings is 3 to 5 times; the volume ratio of the second ethyl ester phase to the water used for the single water washing is 1:0.1 to 0.3;
  • the aqueous phase obtained from the first water washing is used as the fourth aqueous phase;
  • the aqueous phase obtained from the 2nd to 5th water washing 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 fourth ethyl ester phase is 40-60%.
  • the crystallization temperature is 40 to 60° C. and the time is 12 to 30 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 using a hydrolysis system.
  • the present invention performs alkaline hydrolysis in an alkali metal hydroxide-water system, and sucralose-6-acetate, sucralose diester and sucralose-6-acetate are all alkaline hydrolyzed in the presence of a strong alkaline aqueous solution to generate corresponding sucralose and sucralose, and sucralose can continue to be dechlorinated in the presence of a strong alkaline aqueous solution to form sucralose, so that sucralose-6-acetate and impurities (sucralose diester and sucralose-6-acetate) in the raw material liquid 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 adopts a dual system of ethyl acetate-water, and can realize mutual application between the dual systems to extract and remove impurities, enrich sucralose, so that sucralose can be crystallized in ethyl acetate in large quantities, and recover sucralose by repeated application, thereby avoiding the loss of sucralose and greatly improving the overall yield of sucralose.
  • the present invention performs alkaline hydrolysis in an alkali metal hydroxide-water system, which can not only replace the traditional sodium methoxide/methanol reaction system with high hazard, but also save the need to purify sucralose-6-acetate before alkaline hydrolysis, and does not need to perform ozone oxidation, which greatly shortens the process and is safe and environmentally friendly.
  • FIG1 is a process flow chart for preparing crude sucralose using a hydrolysis system
  • FIG. 2 is a detailed process flow chart for preparing crude sucralose using a hydrolysis system.
  • the present invention provides a method for preparing crude sucralose by using a hydrolysis system, comprising the following steps:
  • the raw material liquid is an aqueous solution including sucralose-6-acetate, sucralose diester and tetrachlorosucrose-6-acetate;
  • step (2) washing the second ethyl ester phase with water to obtain a fourth aqueous phase and a third ethyl ester phase, respectively; the fourth aqueous phase is reused in step (2) to dissolve the first ethyl ester phase concentrate;
  • the present invention extracts the raw material liquid with ethyl acetate to obtain a first ethyl ester phase and a first aqueous phase respectively; the first ethyl ester phase is concentrated to obtain a first ethyl ester phase concentrate; the raw material liquid is an aqueous solution including sucralose-6-acetate, sucralose diester and tetrachlorosucrose-6-acetate.
  • the present invention has no special limitation on the preparation method of the raw material liquid.
  • a preparation method for preparing a crude sucrose-6-acetate product using sucrose as an initial raw material well known to those skilled in the art can be adopted. Specifically, sucrose is used as a raw material, N,N-dimethylformamide (DMF) is used as a solvent, organic tin is used as a catalyst, and 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 raw material liquid.
  • DMF N,N-dimethylformamide
  • organic tin is used as a catalyst
  • acetic anhydride is used as an acylating agent to prepare a solution containing sucrose-6-acetate
  • the obtained solution containing sucrose-6-acetate is sequentially chlor
  • the content of sucralose-6-acetate is preferably 50-80 g/L, more preferably 50-75 g/L;
  • the mass ratio of sucralose-6-acetate, sucralose diester and tetrachlorosucrose-6-acetate in the raw material solution is preferably 1:0.06-0.15:0.06-0.15, more preferably 1:0.08-0.1:0.09-0.13;
  • 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 84-140 g/L; the concentration of the organic impurities is preferably 30-80 g/L, more preferably 32-73 g/L.
  • 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, and the content of sucralose-6-acetate in the aqueous phase (i.e., the first aqueous phase) obtained by the last ethyl acetate extraction is less than 0.1 g/L, specifically 5-8 times; the time of a single ethyl acetate extraction is preferably 10-30 min, more preferably 15-25 min; the volume ratio of the raw material liquid to the ethyl acetate used for the single ethyl acetate extraction is preferably 1:0.2-0.5, more preferably 1:0.3-0.4.
  • 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 uses hot ethyl acetate (40-60° C.) to extract the raw material liquid, which can reduce the usage of ethyl acetate and increase the dissolution amount of fat-soluble impurities, so as to increase the subsequent solubility of sucralose in ethyl acetate, thereby improving the crystallization sugar content and the sucralose crystallization yield.
  • 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).
  • concentration time is performed until the ethyl acetate content in the obtained first ethyl ester phase concentrate is ⁇ 0.5 g/L.
  • 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 first ethyl ester phase concentrate, thereby further improving the purity and yield of sucralose.
  • the present invention mixes and dissolves the first ethyl ester phase concentrate with water, and concentrates to obtain a sucralose-6-acetate aqueous solution.
  • the volume ratio of the sucralose-6-acetate aqueous solution to the raw material liquid is preferably 1:0.5-1, and more preferably 1:0.6-0.7.
  • the present invention has no special restrictions 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 60-80°C, and the vacuum degree is preferably -0.1-0.08MPa (gauge pressure).
  • the present invention has no special restrictions on the concentration time, and the content of ethyl acetate in the obtained sucralose-6-acetate aqueous solution is ⁇ 0.5g/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 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 present invention mixes the sucralose-6-acetate aqueous solution with an alkali metal hydroxide to perform an alkaline hydrolysis reaction, neutralizes the obtained reaction solution, and then performs hot filtration to obtain a second aqueous 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, and the pH value during the alkaline hydrolysis reaction can be ensured to be 11-13, and the pH value is more preferably 11.5-12.5, and more preferably 12; the temperature of the alkaline hydrolysis reaction is preferably 0-10°C, more preferably 0-8°C, and more preferably 1-5°C; the time of the alkaline hydrolysis reaction is preferably 3-6h, more preferably 3.5-5.5h, and more preferably 4-5h.
  • the alkaline hydrolysis reaction is carried out under the above conditions, and sucralose diester can be hydrolyzed to generate sucralose, and tetrachlorosucrose-6-acetate can be dechlorinated and hydrolyzed to generate sucralose, and the by-products can also be avoided due to the excessively high pH value of the alkaline hydrolysis reaction or the excessively high temperature of the alkaline hydrolysis reaction.
  • the yield of sucralose is significantly improved, and there is no need to purify the crude aqueous solution of sucralose-6-acetate, which greatly shortens the process flow and reduces the production cost.
  • the neutralizing acid preferably includes hydrochloric acid, and the concentration of the hydrochloric 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 temperature of the hot filtration is preferably 45 to 70° C., more preferably 50 to 70° C.
  • the reaction liquid obtained by the alkaline hydrolysis reaction is neutralized and heated to 45 to 70° C., so that the sucralose mixed in the viscous substance can be dissolved, and then hot filtration can remove insoluble substances such as carbon residue and tar, and can also avoid the sucralose from being caramelized due to excessive temperature.
  • the present invention extracts the second aqueous phase with ethyl acetate to obtain a second ethyl ester phase and a third aqueous phase, respectively.
  • the number of ethyl acetate extractions is preferably 4 to 7 times;
  • the volume ratio of the second aqueous phase to the single ethyl acetate extraction with ethyl acetate is preferably 1:1 to 3, more preferably 1:1.5 to 2.5;
  • the present invention preferably combines the ethyl ester phases obtained by the 1st to 2nd ethyl acetate extractions as the second ethyl ester phase;
  • the ethyl ester phases obtained by the 3rd to 7th ethyl acetate extractions are preferably used for the ethyl acetate extraction of the second aqueous phase in the next batch of crude sucralose preparation process.
  • the ethyl ester phase obtained by the 3rd ethyl acetate extraction is used for the 1st ethyl acetate extraction of the second aqueous phase in the next batch of crude sucralose preparation process
  • the ethyl ester phase obtained by the 3rd ethyl acetate extraction is used for the 1st ethyl acetate extraction of the second aqueous phase in the next batch of crude sucralose preparation process.
  • the ethyl ester phase obtained by the 4 ethyl acetate extractions is used for the 2nd ethyl acetate extraction of the second aqueous phase in the next batch of crude sucralose preparation process
  • the ethyl ester phase obtained by the 5th ethyl acetate extraction is used for the 3rd ethyl acetate extraction of the second aqueous phase in the next batch of crude sucrose preparation process
  • the ethyl ester phase obtained by the 6th ethyl acetate extraction is used for the 4th ethyl acetate extraction of the second aqueous phase in the next batch of crude sucrose preparation process
  • the ethyl ester phase obtained by the 7th ethyl acetate extraction is used for the 5th ethyl acetate extraction of the second aqueous phase in the next batch (i.e., the ethyl ester phases obtained by the 3rd to 7th ethy
  • the present invention washes the second ethyl ester phase with water to obtain a fourth aqueous phase and a third ethyl ester phase respectively; the fourth aqueous phase is reused in step (2) to dissolve the first ethyl ester phase concentrate.
  • the number of water washings is preferably 3 to 5 times; the volume ratio of the second ethyl ester phase to the single water used for water washing is preferably 1:0.1 to 0.3, more preferably 1:0.1 to 0.25; in the present invention, the aqueous phase obtained by the first water washing is preferably used as the fourth aqueous phase, and the aqueous phase obtained by the second to fifth water washings is preferably used for the water washing of the second ethyl ester phase in the next batch of crude sucralose preparation process.
  • the aqueous phase obtained by the second water washing is used for the first water washing of the second ethyl ester phase in the next batch of crude sucralose preparation process, and the aqueous phase obtained by the third water washing is used for the fourth aqueous phase.
  • the obtained aqueous phase is used for the second water washing of the second ethyl ester phase in the preparation process of the next batch of crude sucralose
  • the aqueous phase obtained by the fourth water washing is used for the third water washing of the second ethyl ester phase in the preparation process of the next batch of crude sucrose
  • the aqueous phase obtained by the fifth water washing is used for the fourth water washing of the second ethyl ester phase in the preparation process of the next batch of crude sucrose (that is, the aqueous phases obtained by the second to fifth water washings are used sequentially for the first to fourth water washings of the second ethyl ester phase in the preparation process of the next batch of crude sucralose)
  • the fifth water washing of the second ethyl ester phase of the next batch of crude sucralose is preferably carried out with pure water.
  • the third ethyl ester phase is mixed with ethyl acetate, and azeotropic water removal is performed to obtain a third ethyl ester phase concentrate; the third ethyl ester phase concentrate is mixed with ethyl acetate to obtain a fourth ethyl ester phase.
  • 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 present invention has no special limitation on the concentration conditions, and the third ethyl ester phase concentrate can be concentrated to a water content of less than 0.5wt%.
  • the present invention has no special limitation on the amount of ethyl acetate used, and the sugar content (Bx) of the fourth ethyl ester phase is 40-60%, and the sugar content is more preferably 45-60%.
  • the present invention crystallizes the fourth ethyl ester phase to obtain crude sucralose and the fifth ethyl ester phase, respectively.
  • the crystallization temperature is preferably 40-60°C, more preferably 45-55°C; the crystallization time is preferably 12-35h, more preferably 20-34h.
  • the solubility of sucralose in ethyl acetate is low.
  • the present invention introduces fat-soluble caramel impurities in the system into ethyl acetate during the recycling of the fourth and fifth aqueous phases, which can significantly increase the solubility of sucralose in ethyl acetate, and uses extraction, water washing, and recycling to balance the impurities in the system, so that sucralose is enriched and crystallized in ethyl acetate.
  • the present invention crystallizes sucralose under the above temperature conditions, which has the following two major advantages: first, more sucralose can be obtained without more fat-soluble impurities; second, sucralose will not be caramelized due to the high crystallization temperature, thereby improving the yield of sucralose.
  • 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 washes the fifth ethyl ester phase with water to obtain a fifth aqueous phase and a sixth ethyl ester phase, respectively; the fifth aqueous phase is reused in step (2) to dissolve the first ethyl ester phase concentrate.
  • the present invention has no special limitation on the number of times of washing, and the sucralose content in the sixth ethyl ester phase obtained by the last washing is ⁇ 0.1 g/L, specifically 4 to 8 times.
  • the present invention has no special limitation on the amount of water used for the single washing, and the amount of water used for washing well known to those skilled in the art can be used.
  • the volume ratio of the fifth ethyl ester phase to the single washing water is preferably 1:0.4 to 0.6.
  • the sixth ethyl ester phase is preferably concentrated to obtain recovered ethyl acetate and sugar residue, and the sugar residue is preferably treated as solid waste.
  • the solubility of sucralose in water is relatively high.
  • the present invention can recover the uncrystallized sucralose into the fifth aqueous phase by water washing, and the fifth aqueous phase is recycled, which can improve the yield of sucralose and recover it for reuse.
  • the fat-soluble impurities in the sucralose crystals can be removed to improve its purity.
  • Water-soluble impurities and fat-soluble impurities are all produced by sucrose in a series of reaction processes, so they have a similar main structure to sucralose, so that there is a certain mutual solubility between water-soluble impurities, fat-soluble impurities and sucralose.
  • 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 crystallize therefrom to obtain crude sucralose.
  • the solubility of sucralose in ethyl acetate is much smaller than that in water, so in the pretreatment process, the present invention retains more fat-soluble impurities in the system.
  • multiple times and multiple times of ethyl acetate are used to extract sucralose from the alkaline hydrolysis solution.
  • the concentration of sucralose in the ethyl acetate extracted multiple times shows a gradient decline phenomenon, and the sucralose content in the ethyl acetate phase obtained by the first two extractions is relatively high, which is used as the raw material for sucralose crystallization.
  • the remaining batch of ethyl acetate phase is used for extraction of the next batch of alkaline hydrolyzate, so that a saturated ethyl acetate solution of sucralose can be obtained.
  • the content of water-soluble impurities will affect the crystallization of sucralose in the ethyl acetate phase. Therefore, the first two ethyl acetate phases containing sucralose need to be washed with a small amount of pure water for multiple times to remove the water-soluble impurities therein.
  • the concentration of sucralose in the water phase obtained by washing also decreases with the increase of the number of washings.
  • the washing liquid (the fourth aqueous phase) with the highest concentration of sucralose after the first washing is reused to mix and dissolve with the first ethyl ester phase concentrate, and the remaining washing liquid is used for washing the second ethyl ester phase of the next batch of sucralose.
  • the purpose of the concentrated drying treatment of the third ethyl ester phase obtained after washing is to remove the moisture in the system, because the residual moisture will increase the difficulty of crystallization of sucralose in ethyl acetate.
  • fresh ethyl acetate needs to be added to continue concentrated drying in order to remove moisture.
  • the third ethyl ester concentrate is dissolved to a specific sugar content with fresh ethyl acetate, and the fourth ethyl ester phase obtained can be crystallized to obtain crude sucralose.
  • 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 (250mm ⁇ 4.6mm, 5 ⁇ m); mobile phase: methanol-0.125wt% potassium dihydrogen phosphate aqueous solution (4:6, v/v); column temperature: 40°C; mobile phase flow rate: 1.0mL/min; wherein methanol (chromatographic grade), potassium dihydrogen phosphate (analytical grade), and water are ultrapure water.
  • the preparation method of the raw material solution (referred to as the first aqueous solution) used in the following examples is as follows: sucrose is used as a raw material, DMF is used as a solvent, organotin is used as a catalyst, and acetic anhydride is used as an acylating agent to prepare a solution containing sucrose-6-acetate; the obtained solution containing sucrose-6-acetate is then chlorinated (with thionyl chloride), neutralized with ammonia water, concentrated to dryness in vacuo, and dissolved in water to obtain a raw material solution.
  • the crude sucralose is prepared by using the process flow chart shown in FIG1 and FIG2 , and the specific steps are as follows:
  • Extraction step 1000 mL of the first aqueous solution was placed in a 2 L eggplant-shaped bottle, 300 mL of ethyl acetate was added, and the mixture was stirred and extracted at 50° C. for 15 min. The phases were separated to obtain an organic phase and an aqueous phase. The aqueous phase was subjected to the above extraction step for 6 times. After the extraction was completed, the ester phases were combined as the first ethyl ester phase, and the aqueous phase obtained from the last extraction was the first aqueous phase (the content of sucralose-6-acetate was 0.08 g/L, and the first aqueous phase was subjected to high-salt wastewater treatment).
  • composition of the first aqueous solution is shown in Table 1:
  • the aqueous phase obtained from the first water washing is the fourth aqueous phase
  • the fourth aqueous phase is used in step (2) to replace water and mix with the first ethyl ester phase concentrate;
  • the aqueous phase obtained from the 2nd to 6th water washings are used as the 1st to 5th water washings of the second ethyl ester phase in the preparation process of the next batch of crude sucralose, and the ester phase obtained after the washing is the third ethyl ester phase.
  • the third ethyl ester phase was concentrated and dried at 70° C. and ⁇ 0.1 MPa (gauge pressure).
  • ethyl acetate was added (3 times, 300 mL each time) for dehydration to ensure that the water was completely removed. Ethyl acetate was added to the obtained third ethyl ester phase concentrate to adjust the sugar content Bx to 43%, thereby obtaining a fourth ethyl ester phase.
  • Crystallization step crystallize the fourth ethyl ester phase at 45° C. for 24 h, filter and obtain crude sucralose and 420 mL of the fifth ethyl ester phase (after equilibration four times); wash the fifth ethyl ester phase with water for 6 times (each time with 210 mL of water), the ester phase after washing with water is the sixth ester phase (sucralose content 0.03 g/L), concentrate and dry the sixth ester phase to obtain recovered ethyl acetate and sugar residue; combine the aqueous phases as the fifth aqueous phase, and use the fifth aqueous phase in step (2) to replace water and mix with the first ethyl ester phase concentrate.
  • step (1) the fourth aqueous phase and the fifth aqueous phase were recycled 17 times, wherein "adding water to the obtained first ethyl ester phase concentrate to 1000 mL" in step (1) was modified to "mixing the obtained first ethyl ester phase, the fourth aqueous phase and the fifth aqueous phase"; in step (4), the 1st to 4th ethyl acetate extractions of the second aqueous phase were carried out using the ethyl ester phase obtained by the 3rd to 6th ethyl acetate extractions of the second aqueous phase in the preparation process of the previous batch of crude sucralose, and the 5th to 6th ethyl acetate extractions of the second aqueous phase were carried out using pure ethyl acetate; the 1st to 5th water washings of the second ethyl ester phase were carried out using the
  • Yield mass of sucralose/mass of sucralose-6-acetate completely converted to sucralose ⁇ 100%.
  • both sucralose diester and sucralose-6-acetate can be converted into sucralose after alkaline hydrolysis, and the theoretical maximum yield in Example 1 is 121.18%.
  • the crude sucralose was prepared according to the method of Example 1, which differed from Example 1 in that:
  • step (1) the main components of the first solution used are shown in Table 3, the volume of ethyl acetate for a single extraction is 200 mL, the extraction temperature is 60° C., the extraction time is 20 min, the aqueous phase repeats the above extraction steps 7 times, and the content of sucralose-6-acetate in the first aqueous phase is 0.05 g/L;
  • step (2) sucralose-6-acetate aqueous solution (650 mL, ethyl acetate content of 0.37 g/L) was concentrated and dried at 75°C and -0.09 MPa;
  • step (3) the temperature was lowered to 3°C, the alkaline hydrolysis temperature was 3°C, the alkaline hydrolysis pH was 12.5, the alkaline hydrolysis time was 4 hours, the pH was neutralized to 6.9, the hot filtration temperature was 50°C, and the second aqueous phase (700 mL, sucralose-6-acetate content was 0.03 g/L);
  • step (4) 2100 mL of ethyl acetate was added at a time, and the extraction was performed 5 times.
  • the volume of the second ethyl ester phase was 4250 mL.
  • the ethyl ester phases obtained from the 3rd to 5th ethyl acetate extractions were used as the 1st to 3rd ethyl acetate extractions of the second aqueous phase in the preparation process of the next batch of crude sucralose.
  • the washing times were 5 times, and 425 mL of water was used for a single washing.
  • the aqueous phases obtained from the 2nd to 5th washings of the second ethyl ester phase were used as the 1st to 4th washings of the second ethyl ester phase in the preparation process of the next batch of crude sucralose.
  • the mixture was concentrated and dried at 75°C and -0.08 MPa.
  • the ethyl acetate was added 4 times during the concentration and drying process.
  • the amount of ethyl acetate added at a single time was 1000 mL, and Bx was 50%;
  • step (5) the crystallization temperature is 50°C, the crystallization time is 30h, the volume of the fifth ethyl ester phase is 400mL, the number of water washings is 7 times, the water consumption for a single water washing is 160mL, and the sucralose content in the sixth ethyl ester phase is 0.04g/L;
  • the first to third ethyl acetate extractions of the second aqueous phase utilize the ethyl ester phase obtained by the third to fifth ethyl acetate extractions of the second aqueous phase in the preparation process of the previous batch of crude sucralose, and the fourth to fifth ethyl acetate extractions of the second aqueous phase utilize pure ethyl acetate;
  • the first to fourth water washings of the second ethyl ester phase utilize the aqueous phase obtained by the second to fifth water washings of the second ethyl ester phase in the preparation process of the previous batch of crude sucralose, and the fifth water washing of the second ethyl ester phase utilizes pure water;
  • the purity and yield data of the crude sucralose obtained by recycling 17 times are shown in Table 4:
  • the crude sucralose was prepared according to the method of Example 1, which differed from Example 1 in that:
  • step (1) the main components of the first solution used are shown in Table 5, the volume of ethyl acetate used for a single extraction is 400 mL, the extraction temperature is 40° C., the extraction time is 10 min, the aqueous phase repeats the above extraction steps 5 times, and the content of sucralose-6-acetate in the first aqueous phase is 0.02 g/L;
  • step (2) sucralose-6-acetate aqueous solution (600 mL, ethyl acetate content of 0.23 g/L) was concentrated and dried at 80°C and -0.09 MPa;
  • step (3) the temperature was lowered to 5°C, the alkaline hydrolysis temperature was 10°C, the alkaline hydrolysis pH was 11.0, the alkaline hydrolysis time was 6h, the pH was neutralized to 6.8, the hot filtration temperature was 70°C, and the second aqueous phase (635mL, sucralose-6-acetate content was 0.02g/L);
  • step (4) 635 mL of ethyl acetate was added at a time, and the extraction was performed 7 times.
  • the volume of the second ethyl ester phase was 680 mL.
  • the ethyl ester phases obtained from the 3rd to 7th ethyl acetate extractions were used as the 1st to 5th ethyl acetate extractions of the second aqueous phase in the preparation process of the next batch of crude sucralose.
  • the extraction was washed 7 times, and 68 mL of water was used for each washing.
  • the aqueous phases obtained from the 2nd to 7th washings of the second ethyl ester phase were used as the 1st to 6th washings of the second ethyl ester phase in the preparation process of the next batch of crude sucralose.
  • the extraction was concentrated and dried at 80°C and -0.08 MPa.
  • the number of ethyl acetate additions during the concentration and drying process was 4 times, and the amount of ethyl acetate added at a time was 136 mL.
  • Bx was 40%;
  • step (5) the crystallization temperature is 40° C., the crystallization time is 36 h, the volume of the fifth ethyl ester phase is 500 mL, the number of water washes is 5 times, the water volume of a single water wash is 200 mL, and the sucralose content in the sixth ethyl ester phase is 0.01 g/L;
  • step (6) the 1st to 5th ethyl acetate extractions of the second aqueous phase utilize the ethyl ester phase obtained by the 3rd to 7th ethyl acetate extractions of the second aqueous phase in the preparation process of the previous batch of crude sucralose, and the 6th to 7th ethyl acetate extractions of the second aqueous phase utilize pure ethyl acetate; the 1st to 6th water washings of the second ethyl ester phase utilize the aqueous phase obtained by the 2nd to 7th water washings of the second ethyl ester phase in the preparation process of the previous batch of crude sucralose, and the 7th water washing of the second ethyl ester phase is performed with pure water; the purity and yield data of the crude sucralose obtained by recycling 17 times are shown in Table 6:
  • the crude sucralose was prepared according to the method of Example 1, which differed from Example 1 in that:
  • step (1) the main components of the first solution used are shown in Table 7, the volume of ethyl acetate for a single extraction is 400 mL, the extraction temperature is 55° C., the extraction time is 20 min, the aqueous phase repeats the above extraction steps 6 times, and the content of sucralose-6-acetate in the first aqueous phase is 0.04 g/L;
  • step (2) sucralose-6-acetate aqueous solution (680 mL, ethyl acetate content of 0.37 g/L) was concentrated and dried at 65°C and -0.09 MPa;
  • step (3) the temperature was lowered to 4°C, the alkaline hydrolysis temperature was 4°C, the alkaline hydrolysis pH was 11.7, the alkaline hydrolysis time was 5h, the pH was neutralized to 7, the hot filtration temperature was 65°C, and the second aqueous phase (740mL, sucralose-6-acetate content was 0.01g/L);
  • step (4) 1200 mL of ethyl acetate was added at a time, and the extraction was performed 7 times.
  • the volume of the second ethyl ester phase was 2690 mL.
  • the ethyl ester phases obtained from the 3rd to 7th ethyl acetate extractions were successively used as the 1st to 5th ethyl acetate extractions of the second aqueous phase in the preparation process of the next batch of crude sucralose.
  • the washing times were 5 times, and 800 mL of water was used for a single washing.
  • the aqueous phases obtained from the 2nd to 5th washings of the second ethyl ester phase were successively used as the 1st to 4th washings of the second ethyl ester phase in the preparation process of the next batch of crude sucralose.
  • the mixture was concentrated and dried at 70°C and -0.08 MPa.
  • the ethyl acetate was added 3 times during the concentration and drying process, and the amount of ethyl acetate added at a single time was 600 mL.
  • Bx was 53%;
  • step (5) the crystallization temperature is 50° C., the crystallization time is 28 h, the volume of the fifth ethyl ester phase is 390 mL, the number of water washes is 6 times, the water volume of a single water wash is 200 mL, and the sucralose content in the sixth ethyl ester phase is 0.05 g/L;
  • step (6) the 1st to 5th ethyl acetate extractions of the second aqueous phase utilize the ethyl ester phase obtained by the 3rd to 7th ethyl acetate extractions of the second aqueous phase in the preparation process of the previous batch of crude sucralose, and the 6th to 7th ethyl acetate extractions of the second aqueous phase utilize pure ethyl acetate; the 1st to 4th water washings of the second ethyl ester phase utilize the aqueous phase obtained by the 2nd to 5th water washings of the second ethyl ester phase in the preparation process of the previous batch of crude sucralose, and the 5th water washing of the second ethyl ester phase utilizes pure water; the purity and yield data of the crude sucralose obtained by recycling 17 times are shown in Table 8:
  • the crude sucralose was prepared according to the method of Example 1, which differed from Example 1 in that:
  • step (1) the main components of the first solution used are shown in Table 9, the volume of ethyl acetate for a single extraction is 500 mL, the extraction temperature is 60° C., the extraction time is 10 min, the aqueous phase repeats the above extraction steps 6 times, and the content of sucralose-6-acetate in the first aqueous phase is 0.03 g/L;
  • sucralose-6-acetate aqueous solution 700 mL, ethyl acetate content of 0.50 g/L was concentrated and dried at 60°C and -0.09 MPa;
  • step (3) the temperature was lowered to 0°C, the alkaline hydrolysis temperature was 5°C, the alkaline hydrolysis pH was 13.0, the alkaline hydrolysis time was 3h, and the second aqueous phase (770mL, sucralose-6-acetate content was 0.05g/L);
  • step (4) 1540 mL of ethyl acetate was added at a time, and the extraction was performed 7 times.
  • the volume of the second ethyl ester phase was 3360 mL.
  • the ethyl ester phases obtained from the 3rd to 7th ethyl acetate extractions were used as the 1st to 5th ethyl acetate extractions of the second aqueous phase in the preparation process of the next batch of crude sucralose.
  • the number of water washings was 5 times.
  • the aqueous phases obtained from the 2nd to 5th water washings of the second ethyl ester phase were used as the 1st to 4th water washings of the second ethyl ester phase in the preparation process of the next batch of crude sucralose.
  • the single water washing was performed with 500 mL of water.
  • the mixture was concentrated and dried at 60°C and -0.1 MPa.
  • the number of ethyl acetate additions during the concentration and drying process was 3 times.
  • the amount of ethyl acetate added at a time was 700 mL, and Bx was 60%;
  • step (5) the crystallization temperature is 45° C., the crystallization time is 24 h, the volume of the fifth ethyl ester phase is 360 mL, the number of water washes is 7 times, the water consumption for a single water wash is 150 mL, and the sucralose content in the sixth ethyl ester phase is 0.08 g/L;
  • step (6) the 1st to 5th ethyl acetate extractions of the second aqueous phase utilize the ethyl ester phase obtained by the 3rd to 7th ethyl acetate extractions of the second aqueous phase in the preparation process of the previous batch of crude sucralose, and the 6th to 7th ethyl acetate extractions of the second aqueous phase utilize pure ethyl acetate; the 1st to 4th water washings of the second ethyl ester phase utilize the aqueous phase obtained by the 2nd to 5th water washings of the second ethyl ester phase in the preparation process of the previous batch of crude sucralose, and the 5th water washing of the second ethyl ester phase utilizes pure water; the purity and yield data of the crude sucralose obtained by recycling 17 times are shown in Table 10:
  • the crude sucralose was prepared according to the method of Example 1, which differed from Example 1 in that:
  • step (1) the main components of the first solution used are shown in Table 11, the volume of ethyl acetate for a single extraction is 500 mL, the extraction temperature is 45° C., the extraction time is 20 min, the aqueous phase repeats the above extraction steps 7 times, and the content of sucralose-6-acetate in the first aqueous phase is 0.07 g/L;
  • step (2) sucralose-6-acetate aqueous solution (690 mL, ethyl acetate content of 0.32 g/L) was concentrated and dried under 80° C. and ⁇ 0.08 MPa;
  • step (3) the temperature was lowered to 5°C, the alkaline hydrolysis temperature was 5°C, the alkaline hydrolysis pH was 12.8, the alkaline hydrolysis time was 4h, the pH was neutralized to 6.9, the hot filtration temperature was 55°C, and the second aqueous phase (810mL, sucralose-6-acetate content was 0.02g/L);
  • step (4) 2000 mL of ethyl acetate was added at a time, and the extraction was performed 5 times.
  • the volume of the second ethyl ester phase was 4300 mL.
  • the ethyl ester phases obtained from the 3rd to 5th ethyl acetate extractions were used as the 1st to 3rd ethyl acetate extractions of the second aqueous phase in the preparation process of the next batch of crude sucralose.
  • the washing times were 5 times, and 500 mL of water was used for each washing.
  • the aqueous phases obtained from the 2nd to 5th washings of the second ethyl ester phase were used as the 1st to 4th washings of the second ethyl ester phase in the preparation process of the next batch of crude sucralose.
  • the mixture was concentrated and dried at 65° C. and -0.09 MPa.
  • the ethyl acetate was added 4 times during the concentration and drying process, and the amount of ethyl acetate added at a time was 900 mL.
  • Bx was 57%;
  • step (5) the crystallization temperature is 50° C., the crystallization time is 26 h, the volume of the fifth ethyl ester phase is 370 mL, the number of water washings is 6 times, the water consumption for a single water washing is 180 mL, and the sucralose content in the sixth ethyl ester phase is 0.07 g/L;
  • the first to third ethyl acetate extractions of the second aqueous phase utilize the ethyl ester phase obtained by the third to fifth ethyl acetate extractions of the second aqueous phase in the preparation process of the previous batch of crude sucralose, and the fourth to fifth ethyl acetate extractions of the second aqueous phase utilize pure ethyl acetate;
  • the first to fourth water washings of the second ethyl ester phase utilize the aqueous phase obtained by the second to fifth water washings of the second ethyl ester phase in the preparation process of the previous batch of crude sucralose, and the fifth water washing of the second ethyl ester phase utilizes pure water;
  • the purity and yield data of the crude sucralose obtained by recycling 17 times are shown in Table 12:
  • the crude sucralose was prepared according to the method of Example 1, which differed from Example 1 in that:
  • step (1) the main components of the first solution used are shown in Table 13, the volume of ethyl acetate for a single extraction is 200 mL, the extraction temperature is 60° C., the extraction time is 15 min, the aqueous phase repeats the above extraction steps 7 times, and the content of sucralose-6-acetate in the first aqueous phase is 0.06 g/L;
  • step (2) sucralose-6-acetate aqueous solution (630 mL, ethyl acetate content of 0.22 g/L) was concentrated and dried at 70°C and -0.08 MPa;
  • step (3) the temperature was lowered to 3°C, the alkaline hydrolysis temperature was 3°C, the alkaline hydrolysis pH was 12.4, the alkaline hydrolysis time was 3.5 h, the pH was neutralized to 6.8, the hot filtration temperature was 50°C, and the second aqueous phase (670 mL, sucralose-6-acetate content was 0.05 g/L);
  • step (4) the single amount of ethyl acetate added is 1400 mL, the volume of the second ethyl ester phase is 3100 mL, the number of water washings is 5 times, the single water washing uses 700 mL, the aqueous phase obtained from the 2nd to 5th water washings of the second ethyl ester phase is successively used as the 1st to 4th water washings of the second ethyl ester phase in the preparation process of the next batch of crude sucralose, and concentrated and dried under the conditions of 65°C and -0.09 MPa, the number of ethyl acetate added during the concentrated and dried process is 2 times, the single amount of ethyl acetate added is 800 mL, and Bx is 48%;
  • step (5) the crystallization temperature is 40° C., the crystallization time is 34 h, the volume of the fifth ethyl ester phase is 400 mL, the number of water washes is 5 times, the water volume of a single water wash is 200 mL, and the sucralose content in the sixth ethyl ester phase is 0.04 g/L;
  • step (6) the first to fourth water washes of the second ethyl ester phase were carried out using the aqueous phase obtained by the second to fifth water washes of the second ethyl ester phase in the preparation process of the previous batch of crude sucralose, and the fifth water wash of the second ethyl ester phase was carried out using pure water; the purity and yield data of the crude sucralose obtained by recycling 17 times are shown in Table 14:
  • the crude sucralose was prepared according to the method of Example 1, which differed from Example 1 in that:
  • step (1) the main components of the first solution used are shown in Table 15, the volume of ethyl acetate for a single extraction is 300 mL, the extraction temperature is 40° C., the extraction time is 20 min, the aqueous phase repeats the above extraction steps 5 times, and the content of sucralose-6-acetate in the first aqueous phase is 0.09 g/L;
  • step (2) sucralose-6-acetate aqueous solution (600 mL, ethyl acetate content of 0.48 g/L) was concentrated and dried at 70°C and -0.09 MPa;
  • step (3) the temperature was lowered to 1°C, the alkaline hydrolysis temperature was 1°C, the alkaline hydrolysis pH was 12.0, the alkaline hydrolysis time was 4.5 h, the pH was neutralized to 7, the hot filtration temperature was 45°C, and the second aqueous phase (640 mL, sucralose-6-acetate content was 0.04 g/L);
  • step (4) 1000 mL of ethyl acetate was added at a time, and the extraction was performed 7 times.
  • the volume of the second ethyl ester phase was 2200 mL.
  • the ethyl ester phases obtained from the 3rd to 7th ethyl acetate extractions were used as the 1st to 5th ethyl acetate extractions of the second aqueous phase in the preparation process of the next batch of crude sucralose.
  • the washing times were 5 times, and 300 mL of water was used for each washing.
  • the aqueous phases obtained from the 2nd to 5th washings of the second ethyl ester phase were used as the 1st to 4th washings of the second ethyl ester phase in the preparation process of the next batch of crude sucralose.
  • the mixture was concentrated and dried at 80° C. and -0.08 MPa.
  • the ethyl acetate was added twice during the concentration and drying process, and the amount of ethyl acetate added at a time was 800 mL.
  • Bx was 45%;
  • step (5) the crystallization temperature is 40° C., the crystallization time is 32 h, the volume of the fifth ethyl ester phase is 410 mL, the number of water washes is 5 times, the water consumption for a single water wash is 220 mL, and the sucralose content in the sixth ethyl ester phase is 0.02 g/L;
  • step (6) the 1st to 5th ethyl acetate extractions of the second aqueous phase utilize the ethyl ester phase obtained by the 3rd to 7th ethyl acetate extractions of the second aqueous phase in the preparation process of the previous batch of crude sucralose, and the 6th to 7th ethyl acetate extractions of the second aqueous phase utilize pure ethyl acetate; the 1st to 4th water washings of the second ethyl ester phase utilize the aqueous phase obtained by the 2nd to 5th water washings of the second ethyl ester phase in the preparation process of the previous batch of crude sucralose, and the 5th water washing of the second ethyl ester phase utilizes pure water; the purity and yield data of the crude sucralose obtained by recycling 17 times are shown in Table 16:
  • Theoretical maximum yield is 118.35%.
  • sucralose and impurities are in a state of equilibrium in the ethyl ester phase, that is, the sucralose yield is above 105% by controlling the following conditions: (1) the sucralose-6-acetate content in the second aqueous phase after alkaline hydrolysis reaches the specified standard; (2) the residual sugar in the first aqueous phase and the third aqueous phase reaches the specified standard; (3) during crystallization, the water content in the ethyl acetate phase reaches the specified standard; (4) the residual sugar in the sixth ethyl ester phase needs to meet the established standard; (5) the crystallization conditions are stable.
  • sucralose can achieve a yield of more than 110% (based on the conversion of sucralose-6-acetate into sucralose); the mutual washing and application of the ester phase and the aqueous phase can avoid the loss caused by the residue of sucralose in the sugar residue and wastewater to the greatest extent. Moreover, the residual sucralose contained in the fourth aqueous phase and the fifth aqueous phase is fully utilized, thereby improving the yield of sucralose.
  • the yield is low because the ethyl acetate and water circulating in the system contain low components that can be converted into sucralose.
  • the yield will exceed 100%.
  • the first aqueous solution also includes other components (sucralose diester and sucralose-6-acetate) that can be converted into sucralose.
  • the method provided by the present invention can convert sucralose diester and sucralose-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 first aqueous solution as a raw material, and there is no need to purify the crude sucralose-6-acetate. The process is simpler, and the loss of sucralose-6-acetate caused by the need to purify sucralose-6-acetate before alkaline hydrolysis in the traditional process is avoided.
  • the method provided by the present invention has extremely obvious advantages.
  • the present invention stores the aqueous phase (the fourth aqueous phase and the fifth aqueous phase) of a specific step in the production process, and continues to be used to remove ethyl acetate in the alkaline hydrolysis reaction system in the next production process, which can reduce the generation of byproducts acetic acid and ethanol, thereby improving the purity of sucralose; at the same time, the sucralose contained in the fourth aqueous phase and the fifth aqueous phase can be fully utilized by circulating sucralose in the production process without flowing out of the production process, greatly reducing the loss of sucralose and greatly improving the overall yield of sucralose.
  • the yield of sucralose in this process of the crystallization process of the present invention is not high (the ratio of the crystallized product to the crystallization raw material), but the purity of the crude sucralose is high; although the yield of the crystallization process is not high, due to the recycling of the fourth aqueous phase and the fifth aqueous phase, the present production process introduces the fourth aqueous phase and the fifth aqueous phase of the previous process (the uncrystallized sucralose in this process will enter the next production process), so from the perspective of the entire production process, the ratio of the obtained crude sucralose yield to the theoretical yield (theoretical yield calculated based on the input raw materials) is significantly higher than that of the existing production process.
  • the purity of crude sucralose is improved, the difficulty of subsequent treatment is reduced, and the overall yield of the overall raw materials of sucralose is improved.
  • a strong alkali metal oxide is used in the alkaline hydrolysis step to replace the traditional sodium methoxide/methanol reaction system with high hazard, which is safe and environmentally friendly.
  • the fat-soluble caramel impurities in the system are introduced into ethyl acetate, which reduces the difficulty of impurity removal and waste treatment on the one hand, and increases the solubility of sucralose in ethyl acetate on the other hand, so that sucralose is fully enriched and crystallized during the crystallization process, thereby improving the yield.
  • the method provided by the present invention uses an alkali metal hydroxide and water system for alkaline hydrolysis, and an ethyl acetate/water dual system (the fourth aqueous phase and the fifth aqueous phase are recycled to dissolve the first ethyl ester phase concentrate) 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 of sucralose-6-acetate before alkaline hydrolysis 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-乙酸酯的水溶液为原料液，在碱金属氢氧化物和水体系中进行碱解，能够将原料液中的三氯蔗糖-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。

Description

一种利用水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，特别涉及一种利用水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，外观为白色结晶粉末或颗粒，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，口感纯正、不参与人体新陈代谢，可供糖尿病人、心脑血管疾病患者及老年人使用的“零卡”糖，其还具有稳定性好和安全性高等特点，被广泛应用于食品、饮料、日化和医药等多个领域。
目前，三氯蔗糖的生产工艺主要通过以下五步反应：(1)酯化反应：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，乙酸酐为酰化剂进行的酯化反应，反应产物为蔗糖-6-乙酯；(2)氯化反应：以蔗糖-6-乙酯为原料，DMF和三氯乙烷为溶剂，威式试剂或光气为氯化剂进行氯化反应，反应产物为三氯蔗糖-6-乙酸酯；(3)三氯蔗糖-6-乙酸酯提纯：利用液碱或氨水将氯化反应获得的氯化液中和，然后蒸发回收溶剂DMF和三氯乙烷，再加水溶解，再经多级分离提纯等处理步骤获得三氯蔗糖-6-乙酸酯纯品；(4)醇解反应：以高纯度三氯蔗糖-6-乙酸酯为原料，甲醇钠为催化剂，甲醇为溶剂，进行醇解反应，然后和反应物，得到三氯蔗糖；(5)分离提纯：醇解后获得的三氯蔗糖-6-乙酸酯溶液，经脱溶、除杂、结晶和烘干，得到三氯蔗糖纯品。
在以三氯蔗糖-6-乙酸酯为原料进行醇解过程中，需采用高纯度(99％以上)的三氯蔗糖-6-乙酸酯且在无水条件下进行，这是由于过多的杂质会严重影响后续三氯蔗糖的提纯，而且水的存在会影响三氯蔗糖-6-乙酯的酯交换反应，致使三氯蔗糖-6-乙酯水解并生成乙酸，影响后续三氯蔗糖的品质以及降低收率。例如，中国专利CN113004345A、CN104004032A、CN112805291A、CN1814609A、CN101012250A、CN102321122A和CN112771059A、均以高纯度三氯蔗糖-6-乙酸酯为原料经醇解反应制备三氯蔗糖。然而，三氯蔗糖-6-乙酸酯在提纯过程中损耗较大，进而导致三 氯蔗糖的收率比较低。
中国专利CN113717237A公开了以含有三氯蔗糖-6-乙酸酯的中和液为原料，进行乙酸乙酯萃取，将所得含有三氯蔗糖-6-乙酸酯的酯相进行臭氧氧化，除去部分杂质，然后采用氢氧化钠/水体系进行碱解，然后提纯，得到三氯蔗糖。该专利虽然以含有三氯蔗糖-6-乙酸酯的中和液作为原料，其摩尔收率为103.7～105.1％，然而需要进行臭氧氧化，会对环境以及人体造成不利影响。
发明内容
有鉴于此，本发明的目的在于提供一种利用水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且安全环保。
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水解体系制备三氯蔗糖粗品的方法，包括以下步骤：
(1)将原料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，得到第一乙酯相浓缩物；所述原料液为包括三氯蔗糖-6-乙酸酯、三氯蔗糖双酯和四氯蔗糖-6-乙酸酯的水溶液；
(2)将所述第一乙酯相浓缩物与水混合溶解，进行浓缩，得到三氯蔗糖-6-乙酸酯水溶液；
(3)将所述三氯蔗糖-6-乙酸酯水溶液与碱金属氢氧化物混合，进行碱解反应，将得到的反应液进行中和后热过滤，得到第二水相；
(4)将所述第二水相进行乙酸乙酯萃取，分别得到第二乙酯相和第三水相；
(5)将所述第二乙酯相进行水洗，分别得到第四水相和第三乙酯相；所述第四水相回用于步骤(2)中用于溶解所述第一乙酯相浓缩物；
(6)将所述第三乙酯相与乙酸乙酯混合，进行共沸除水，得到第三乙酯相浓缩物；将所述第三乙酯相浓缩物与乙酸乙酯混合，得到第四乙酯相；
(7)将所述第四乙酯相进行结晶，分别得到三氯蔗糖粗品和第五乙酯相；
(8)将所述第五乙酯相进行水洗，分别得到第五水相和第六乙酯相； 所述第五水相回用于步骤(2)用于溶解所述第一乙酯相浓缩物。
优选地，步骤(1)中，所述乙酸乙酯萃取的温度为40～60℃，萃取次数为5～8次；所述原料液与单次乙酸乙酯萃取用乙酸乙酯的体积比为1：0.2～0.4。
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(2)中，所述三氯蔗糖-6-乙酸酯水溶液中乙酸乙酯的含量＜0.5g/L。
优选地，步骤(3)中，所述碱解反应的pH值为11～13，温度为0～10℃，时间3～6h。
优选地，步骤(3)中，所述热过滤的温度为45～70℃。
优选地，步骤(4)中，所述乙酸乙酯萃取的次数为4～7次；所述第二水相与乙酸乙酯萃取单次用乙酸乙酯的体积比为1：1～3；
将第1～2次乙酸乙酯萃取得到的乙酯相合并作为第二乙酯相；
将第3～7次乙酸乙酯萃取得到的乙酯相用于下一批次三氯蔗糖粗品制备过程中所述第二水相的乙酸乙酯萃取。
优选地，步骤(4)中，所述第三水相中三氯蔗糖含量<0.5g/L。
优选地，步骤(5)中，所述水洗的次数为3～5次；所述第二乙酯相与水洗的单次用水的体积比为1：0.1～0.3；
将第1次水洗得到的水相作为第四水相；
将第2～5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(5)中，所述第三水相中的三氯蔗糖的含量＜0.5g/L。
优选地，步骤(6)中，所述第三乙酯相浓缩液的水含量＜0.5wt％。
优选地，步骤(6)中，所述第四乙酯相的糖度为40～60％。
优选地，步骤(7)中，所述结晶的温度为40～60℃，时间12～30h。
优选地，步骤(8)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水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-水体系下进行碱解，三氯蔗糖-6-乙酸酯、三氯蔗糖双酯和四氯蔗糖-6-乙酸酯均会在强碱水溶液存在的情况下碱解，生成对应的 三氯蔗糖和四氯蔗糖，四氯蔗糖可以在强碱水溶液存在的情况下继续脱氯形成三氯蔗糖，使得原料液中的三氯蔗糖-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。本发明采用乙酸乙酯-水的双重体系，可将实现双体系间的相互套用萃取除杂，富集三氯蔗糖，从而使三氯蔗糖能够在乙酸乙酯中大量结晶，并通过反复套用的方式回收三氯蔗糖，避免了三氯蔗糖的损失，大大提高了三氯蔗糖的整体收率。而且，本发明以在碱金属氢氧化物-水体系下进行碱解，不仅可以替代传统的具有较高危害性的甲醇钠/甲醇反应体系，还可省去碱解前需要将三氯蔗糖-6-乙酸酯提纯，也无需进行臭氧氧化，大大缩短流程，且安全环保。
附图说明
图1为利用水解体系制备三氯蔗糖粗品的工艺流程图；
图2为利用水解体系制备三氯蔗糖粗品的详细工艺流程图。
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水解体系制备三氯蔗糖粗品的方法，包括以下步骤：
(1)将原料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，得到第一乙酯相浓缩物；所述原料液为包括三氯蔗糖-6-乙酸酯、三氯蔗糖双酯和四氯蔗糖-6-乙酸酯的水溶液；
(2)将所述第一乙酯相浓缩物与水混合溶解，进行浓缩，得到三氯蔗糖-6-乙酸酯水溶液；
(3)将所述三氯蔗糖-6-乙酸酯水溶液与碱金属氢氧化物混合，进行碱解反应，将得到的反应液进行中和后热过滤，得到第二水相；
(4)将所述第二水相进行乙酸乙酯萃取，分别得到第二乙酯相和第三水相；
(5)将所述第二乙酯相进行水洗，分别得到第四水相和第三乙酯相；所述第四水相回用于步骤(2)中用于溶解所述第一乙酯相浓缩物；
(6)将所述第三乙酯相与乙酸乙酯混合，进行共沸除水，得到第三乙酯相浓缩物；将所述第三乙酯相浓缩物与乙酸乙酯混合，得到第四乙酯相；
(7)将所述第四乙酯相进行结晶，分别得到三氯蔗糖粗品和第五乙酯相；
(8)将所述第五乙酯相进行水洗，分别得到第五水相和第六乙酯相；所述第五水相回用于步骤(2)用于溶解所述第一乙酯相浓缩物。
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。
本发明将原料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，得到第一乙酯相浓缩物；所述原料液为包括三氯蔗糖-6-乙酸酯、三氯蔗糖双酯和四氯蔗糖-6-乙酸酯的水溶液。
本发明对于所述原料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，得到原料液。
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50～75g/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1：0.06～0.15：0.06～0.15，更优选为1：0.08～0.1：0.09～0.13；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84～140g/L；所述有机杂质的浓度优选为30～80g/L，更优选为32～73g/L。
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，以最后一次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5～8次；单次乙酸乙酯萃取的时间优选为10～30min，更优选为15～25min；所述原料液与单次乙酸乙酯萃取用乙酸乙酯的体积比优选为1：0.2～0.5，更优选为1：0.3～0.4。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。
本发明采用热的乙酸乙酯(40～60℃)对原料液进行萃取，能够减少乙酸乙酯的使用量，同时增加脂溶性杂质的溶解量，以利于增加后续三氯蔗糖在乙酸乙酯中的溶解度，进而提高结晶糖度及三氯蔗糖结晶收率。
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，浓缩至所得第一乙酯相浓缩物中乙酸乙酯含量<0.5g/L即可。本发明通过控制第一乙酯相浓缩物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。
得到第一乙酯相浓缩物后，本发明将所述第一乙酯相浓缩物与水混合溶解，进行浓缩，得到三氯蔗糖-6-乙酸酯水溶液。在本发明中，所述三氯蔗糖-6-乙酸酯水溶液与原料液体积比优选为1：0.5～1，更优选为1：0.6～0.7。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，浓缩至所得三氯蔗糖-6-乙酸酯水溶液中乙酸乙酯的含量＜0.5g/L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。
得到三氯蔗糖-6-乙酸酯水溶液后，本发明将所述三氯蔗糖-6-乙酸酯水溶液与碱金属氢氧化物混合，进行碱解反应，将得到的反应液进行中和后热过滤，得到第二水相。
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11～13即可，所述pH值更优选为11.5～12.5，进一步优选为12； 所述碱解反应的温度优选为0～10℃，更优选为0～8℃，进一步优选为1～5℃；所述碱解反应的时间优选为3～6h，更优选为3.5～5.5h，进一步优选为4～5h。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。与以纯三氯蔗糖-6-乙酸酯为原料相比，三氯蔗糖的收率显著提高，而且无需对三氯蔗糖-6-乙酸酯粗品水溶液进行提纯，大大缩短了工艺流程并降低了生产成本。
在本发明中，所述中和用酸优选包括盐酸，所述盐酸的浓度优选为优选为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。
在本发明中，所述热过滤的温度优选为45～70℃，更优选为50～70℃。碱解完成后会产生粘稠物，粘稠物中会夹杂大量的三氯蔗糖，本发明对碱解反应得到的反应液中和后加热至45～70℃，能够使得粘稠物中夹杂的三氯蔗糖溶解，然后进行热过滤能够去除碳渣、焦油等不溶物，同时还能够避免温度过高导致三氯蔗糖焦化。
得到第二水相后，本发明将所述第二水相进行乙酸乙酯萃取，分别得到第二乙酯相和第三水相。在本发明中，所述乙酸乙酯萃取的次数优选为4～7次；所述第二水相与乙酸乙酯萃取单次用乙酸乙酯的体积比优选为1：1～3，更优选为1:1.5～2.5；本发明优选将第1～2次乙酸乙酯萃取得到的乙酯相合并作为第二乙酯相；优选将第3～7次乙酸乙酯萃取所得乙酯相用于下一批次三氯蔗糖粗品制备过程中第二水相的乙酸乙酯萃取，具体的，第3次乙酸乙酯萃取所得乙酯相用于下一批次三氯蔗糖粗品制备过程中第二水相的第1次乙酸乙酯萃取，第4次乙酸乙酯萃取所得乙酯相用于下一批次三氯蔗糖粗品制备过程中第二水相的第2次乙酸乙酯萃取，第5次乙酸乙酯萃取所得乙酯相用于下一批次蔗糖粗品制备过程中第二水相的第3次乙酸乙酯萃取，第6次乙酸乙酯萃取所得乙酯相用于下一批次蔗糖粗品制备过程中第二水相的第4次乙酸乙酯萃取，第7次乙酸乙酯萃取所得乙酯相用于下一批次第二水相的第5次乙酸乙酯萃取(即第3～7次乙酸乙酯萃取所得乙酯相依次用于下一批次三氯蔗糖粗品制备过程中第 二水相的第1～5次乙酸乙酯萃取)，下一批次三氯蔗糖粗品的第二水相的第6～7次乙酸乙酯萃取优选利用纯乙酸乙酯进行。在本发明中，所述第三水相中三氯蔗糖含量优选<0.5g/L。
得到第二乙酯相后，本发明将所述第二乙酯相进行水洗，分别得到第四水相和第三乙酯相；所述第四水相回用于步骤(2)中用于溶解所述第一乙酯相浓缩物。
在本发明中，所述水洗的次数优选为3～5次；所述第二乙酯相与水洗的单次用水的体积比优选为1：0.1～0.3，更优选为1：0.1～0.25；本发明优选将第1次水洗得到的水相作为第四水相，优选将第2～5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水洗，具体的，第2次水洗所得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3次水洗所得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4次水洗所得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5次水洗所得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(即第2～5次水洗所得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1～4次水洗)，下一批次三氯蔗糖粗品的第二乙酯相的第5次水洗优选利用纯水进行。
将所述第三乙酯相与乙酸乙酯混合，进行共沸除水，得到第三乙酯相浓缩物；将所述第三乙酯相浓缩物与乙酸乙酯混合，得到第四乙酯相。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，本发明对于所述浓缩的条件没有特殊限定，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，以所述第四乙酯相的糖度(Bx)为40～60％为准，所述糖度更优选为45～60％。
得到第四乙酯相后，本发明将所述第四乙酯相进行结晶，分别得到三氯蔗糖粗品和第五乙酯相。在本发明中，所述结晶的温度优选为40～60℃，更优选为45～55℃；所述结晶的时间优选为12～35h，更优选为20～34h。三氯蔗糖在乙酸乙酯中的溶解度较低，本发明通过在第四水相和第五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，从而使得三氯蔗糖在乙酸乙酯中富集并结晶。而且，本发明在上述温度条件下对三氯蔗糖进行结晶，具有以下两大优势：一是可获得较多的三氯蔗糖且不会夹杂较多的脂溶性杂质；二是不会因为结晶温度较高而导致三氯蔗糖焦化，从而提高了三氯蔗糖的收率。
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，本发明将所述第五乙酯相进行水洗，分别得到第五水相和第六乙酯相；所述第五水相回用于步骤(2)用于溶解所述第一乙酯相浓缩物。本发明对于所述水洗的次数没有特殊限定，以最后一次水洗所得第六乙酯相中三氯蔗糖含量<0.1g/L为准，具体如4～8次。本发明对于所述水洗的单次用水量没有特殊限定，采用本领域技术人员熟知的水洗用水的用量即可，在本发明的具体实施例中，所述第五乙酯相与水洗的单次用水的体积比优选为1：0.4～0.6。在本发明中，所述第六乙酯相优选进行浓缩，得到回收乙酸乙酯和糖渣，所述糖渣优选进行固废处理。结晶完成后，第五乙酯相中脂溶性杂质较多，三氯蔗糖在水中的溶解度较高，本发明采用水洗的方式能够将未结晶的三氯蔗糖回收至第五水相中，将第五水相进行循环利用，能够提高三氯蔗糖的收率回收套用，同时还能够将三氯蔗糖晶体中的脂溶性杂质排除，提高其纯度。
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。具体的，三氯蔗糖在乙酸乙酯中的溶解度远小于在水中的溶解度，因此在前处理过程中，本发明将较多的脂溶性杂质保留在体系中。碱解反应后，采用多倍、多次的乙酸乙酯将三氯蔗糖从碱解液中萃取出来。此时，三氯蔗糖在多次萃取的乙酸乙酯中的浓度呈现梯度下降的现象，前两次萃取所得乙酸乙酯相中的三氯蔗糖含量较高，作为三氯蔗糖结晶的原料。剩余批次的乙酸乙 酯相用于下一批次的碱解液的萃取，这样可以获得饱和的三氯蔗糖乙酸乙酯溶液。水溶性杂质的含量会影响三氯蔗糖在乙酸乙酯相中的结晶，因此，前两次的含有三氯蔗糖的乙酸乙酯相需要少量纯水多次水洗，从而去除其中的水溶性杂质。水洗所得水相中的三氯蔗糖浓度也随着水洗次数的增加而减少，为了回收此部分三氯蔗糖，将第一次水洗且含三氯蔗糖浓度最高的水洗液(第四水相)回用至与所述第一乙酯相浓缩物混合溶解，剩余水洗液用于下一批次三氯蔗糖第二乙酯相的水洗。水洗后所得第三乙酯相进行浓干处理的目的是除尽体系中的水分，这是由于水分的残留会增加三氯蔗糖在乙酸乙酯中结晶的难度。浓干之后还需要添加新鲜的乙酸乙酯继续浓干，目的是为了除尽水分，此时再用新鲜的乙酸乙酯溶解第三乙酯浓缩物至特定糖度，所得第四乙酯相即可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：Agilent XDB 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原料液(记为第一水溶液)的制备方法：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；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、加水溶解，得到原料液。
实施例1
采用图1和图2所示的工艺流程图制备三氯蔗糖粗品，具体步骤如下：
(1)萃取步骤：将1000mL第一水溶液置于2L的茄形瓶中，加入300mL乙酸乙酯，在50℃条件下搅拌萃取15min，分相，得到有机相和 水相，将所述水相重复上述萃取步骤6次，萃取完成后，酯相合并作为第一乙酯相，最后一次萃取所得水相为第一水相(三氯蔗糖-6-乙酸酯含量为0.08g/L，第一水相进行高盐废水处理)。
其中，第一水溶液的成分如表1所示：
表1第一水溶液的成分
组分 含量
三氯蔗糖-6-乙酸酯 52.0g/L
三氯蔗糖双酯 4.7g/L
四氯蔗糖-6-乙酸酯 5.7g/L
NH 4Cl 84.2g/L
其他有机杂质 30.1g/L
水 84.2％
(2)浓干步骤：将所述第一乙酯相在80℃、-0.08MPa条件下真空浓缩至干(简写为浓干)，在所得第一乙酯相浓缩物中加入水至1000mL，在上述条件下浓缩至600mL，得到三氯蔗糖-6-乙酸酯水溶液(乙酸乙酯含量为0.41g/L)，然后转移至1000mL三口烧瓶中。
(3)碱解步骤：将所得三氯蔗糖-6-乙酸酯水溶液降温至1℃，然后滴加浓度为32wt％的氢氧化钠水溶液)混合均匀，在1℃条件下碱解5h，碱解过程中保持体系的pH值为12.3，碱解结束后滴加浓度为30wt％的稀盐酸中和至pH＝7，加热至50℃进行热过滤，得到第二水相(650mL，三氯蔗糖-6-乙酸酯含量为0.04g/L)和滤渣(固废处理)；
(4)分离步骤：向所述第二水相中加入1.3L乙酸乙酯，在50℃条件下搅拌萃取15min，所得水相重复上述萃取操作，共萃取6次，第1～2次萃取得到的酯相合并作为第二乙酯相(2.8L)，第3～6次乙酸乙酯萃取得到的乙酯相依次作为下一批次三氯蔗糖粗品的制备过程中第二水相的第1～4次乙酸乙酯萃取。在所述第二乙酯相中加入550mL水进行水洗，水洗6次，第1次水洗所得水相为第四水相，所述第四水相用于步骤(2)中代替水与所述第一乙酯相浓缩物混合；第2～6次水洗得到的水相依次下一批次三氯蔗糖粗品的制备过程中第二乙酯相的第1～5水洗，水洗结束后所得酯相为第三乙酯相。将所述第三乙酯相在70℃、-0.1MPa(表压) 条件下浓干，浓干过程中加入乙酸乙酯(加入次数为3次，每次加入300mL)进行脱水以保证水分完全去除，在所得第三乙酯相浓缩物中加入乙酸乙酯调节糖度Bx为43％，得到第四乙酯相。
(5)结晶步骤：将所述第四乙酯相在45℃条件下结晶24h，抽滤，分别得到三氯蔗糖粗品和第五乙酯相420mL(套用4次平衡后)；将所述第五乙酯相水洗6次(每次水用量为210mL)，水洗后的酯相为第六酯相(三氯蔗糖含量0.03g/L)，将所述第六酯相进行浓干，分别得到回收乙酸乙酯和糖渣；合并水相作为第五水相，所述第五水相用于步骤(2)中代替水与所述第一乙酯相浓缩物混合。
(6)按照步骤(1)～(5)的操作(记为循环利用0次)，将所述第四水相、第五水相循环利用17次，其中，将步骤(1)中的“在所得第一乙酯相浓缩物中加入水至1000mL”修改为“将所得第一乙酯相、所述第四水相和第五水相混合”；步骤(4)中，第二水相的第1～4次乙酸乙酯萃取利用上一批次三氯蔗糖粗品的制备过程中第二水相的第3～6次乙酸乙酯萃取得到的乙酯相，第二水相的第5～6次乙酸乙酯萃取利用纯乙酸乙酯进行；第二乙酯相的第1～5水洗利用上一批次三氯蔗糖粗品的制备过程中第二乙酯相的第2～6次水洗得到的水相，第二乙酯相的第6次水洗利用纯水进行；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 PCTCN2022126186-appb-000001
Figure PCTCN2022126186-appb-000002
注：收率＝三氯蔗糖的质量/三氯蔗糖-6-乙酸酯完全转化成三氯蔗糖的质量×100％。第一水溶液中，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121.18％。
实施例2
按照实施例1的方法制备三氯蔗糖粗品，与实施例1的区别在于：
步骤(1)中，使用的第一溶液的主要成分如表3所示，单次萃取用乙酸乙酯体积为200mL，萃取温度为60℃，萃取时间为20min，水相重复上述萃取步骤7次，第一水相中三氯蔗糖-6-乙酸酯含量为0.05g/L；
表3第一溶液成分表
组分 含量
三氯蔗糖-6-乙酸酯 65.0g/L
三氯蔗糖双酯 5.1g/L
四氯蔗糖-6-乙酸酯 6.0g/L
NH 4Cl 102.3g/L
其他有机杂质 37.6g/L
水 76.9％
步骤(2)中，在75℃、-0.09MPa条件下浓干，三氯蔗糖-6-乙酸酯水溶液(650mL，乙酸乙酯含量为0.37g/L)；
步骤(3)中，降温至3℃，碱解温度为3℃，碱解pH＝12.5，碱解时间为4h，中和至pH＝6.9，热过滤温度为50℃，第二水相(700mL，三氯蔗糖-6-乙酸酯含量为0.03g/L)；
步骤(4)中，乙酸乙酯单次加入量2100mL，萃取5次，第二乙酯相体积为4250mL，第3～5次乙酸乙酯萃取得到的乙酯相依次作为下一批次三氯蔗糖粗品的制备过程中第二水相的第1～3次乙酸乙酯萃取，水洗次数为5次，单次水洗用水425mL，第二乙酯相的第2～5次水洗得到的水相依次下一批次三氯蔗糖粗品的制备过程中第二乙酯相的第1～4水洗，在75℃、-0.08MPa条件下浓干，浓干过程中乙酸乙酯加入次数为4次，单次加入乙酸乙酯量为1000mL，Bx为50％；
步骤(5)中，结晶温度为50℃，结晶时间为30h，第五乙酯相体积 为400mL，水洗次数为7次，单次水洗用水量为160mL，第六乙酯相中三氯蔗糖含量为0.04g/L；
步骤(6)中，第二水相的第1～3次乙酸乙酯萃取利用上一批次三氯蔗糖粗品的制备过程中第二水相的第3～5次乙酸乙酯萃取得到的乙酯相，第二水相的第4～5次乙酸乙酯萃取利用纯乙酸乙酯进行；第二乙酯相的第1～4水洗利用上一批次三氯蔗糖粗品的制备过程中第二乙酯相的第2～5次水洗得到的水相，第二乙酯相的第5次水洗利用纯水进行；循环利用17次得到的三氯蔗糖粗品的纯度及收率数据如表4所示：
表4三氯蔗糖粗品纯度及收率
Figure PCTCN2022126186-appb-000003
注：理论最大收率115.72％。
实施例3
按照实施例1的方法制备三氯蔗糖粗品，与实施例1的区别在于：
步骤(1)中，使用的第一溶液的主要成分如表5所示，单次萃取用乙酸乙酯体积为400mL，萃取温度为40℃，萃取时间为10min，水相重复上述萃取步骤5次，第一水相中三氯蔗糖-6-乙酸酯含量为0.02g/L；
表5第一溶液成分表
组分 含量
三氯蔗糖-6-乙酸酯 50.0g/L
三氯蔗糖双酯 5.2g/L
四氯蔗糖-6-乙酸酯 6.3g/L
NH 4Cl 84.9g/L
其他有机杂质 36.7g/L
水 83.7％
步骤(2)中，在80℃、-0.09MPa条件下浓干，三氯蔗糖-6-乙酸酯水溶液(600mL，乙酸乙酯含量为0.23g/L)；
步骤(3)中，降温至5℃，碱解温度为10℃，碱解pH＝11.0，碱解时间为6h，中和至pH＝6.8，热过滤温度为70℃，第二水相(635mL，三氯蔗糖-6-乙酸酯含量为0.02g/L)；
步骤(4)中，乙酸乙酯单次加入量635mL，萃取7次，第二乙酯相体积为680mL，第3～7次乙酸乙酯萃取得到的乙酯相依次作为下一批次三氯蔗糖粗品的制备过程中第二水相的第1～5次乙酸乙酯萃取，水洗次数为7次，单次水洗用水68mL，第二乙酯相的第2～7次水洗得到的水相依次下一批次三氯蔗糖粗品的制备过程中第二乙酯相的第1～6水洗，在80℃、-0.08MPa条件下浓干，浓干过程中乙酸乙酯加入次数为4次，单次加入乙酸乙酯量为136mL，Bx为40％；
步骤(5)中，结晶温度为40℃，结晶时间为36h，第五乙酯相体积为500mL，水洗次数为5次，单次水洗用水量为200mL，第六乙酯相中三氯蔗糖含量为0.01g/L；
步骤(6)中，第二水相的第1～5次乙酸乙酯萃取利用上一批次三氯蔗糖粗品的制备过程中第二水相的第3～7次乙酸乙酯萃取得到的乙酯相，第二水相的第6～7次乙酸乙酯萃取利用纯乙酸乙酯进行；第二乙酯相的第1～6水洗利用上一批次三氯蔗糖粗品的制备过程中第二乙酯相的第2～7次水洗得到的水相，第二乙酯相的第7次水洗利用纯水进行；循环利用17次得到的三氯蔗糖粗品的纯度及收率数据如表6所示：
表6三氯蔗糖粗品纯度及收率
Figure PCTCN2022126186-appb-000004
Figure PCTCN2022126186-appb-000005
注：理论最大收率121.18％。
实施例4
按照实施例1的方法制备三氯蔗糖粗品，与实施例1的区别在于：
步骤(1)中，使用的第一溶液的主要成分如表7所示，单次萃取用乙酸乙酯体积为400mL，萃取温度为55℃，萃取时间为20min，水相重复上述萃取步骤6次，第一水相中三氯蔗糖-6-乙酸酯含量为0.04g/L；
表7第一溶液成分表
组分 含量
三氯蔗糖-6-乙酸酯 71.2g/L
三氯蔗糖双酯 6.3g/L
四氯蔗糖-6-乙酸酯 7.2g/L
NH 4Cl 115.3g/L
其他有机杂质 52.3g/L
水 77.5％
步骤(2)中，在65℃、-0.09MPa条件下浓干，三氯蔗糖-6-乙酸酯水溶液(680mL，乙酸乙酯含量为0.37g/L)；
步骤(3)中，降温至4℃，碱解温度为4℃，碱解pH＝11.7，碱解时间为5h，中和至pH＝7，热过滤温度为65℃，第二水相(740mL，三氯蔗糖-6-乙酸酯含量为0.01g/L)；
步骤(4)中，乙酸乙酯单次加入量1200mL，萃取7次，第二乙酯相体积为2690mL，第3～7次乙酸乙酯萃取得到的乙酯相依次作为下一批 次三氯蔗糖粗品的制备过程中第二水相的第1～5次乙酸乙酯萃取，水洗次数为5次，单次水洗用水800mL，第二乙酯相的第2～5次水洗得到的水相依次下一批次三氯蔗糖粗品的制备过程中第二乙酯相的第1～4水洗，在70℃、-0.08MPa条件下浓干，浓干过程中乙酸乙酯加入次数为3次，单次加入乙酸乙酯量为600mL，Bx为53％；
步骤(5)中，结晶温度为50℃，结晶时间为28h，第五乙酯相体积为390mL，水洗次数为6次，单次水洗用水量为200mL，第六乙酯相中三氯蔗糖含量为0.05g/L；
步骤(6)中，第二水相的第1～5次乙酸乙酯萃取利用上一批次三氯蔗糖粗品的制备过程中第二水相的第3～7次乙酸乙酯萃取得到的乙酯相，第二水相的第6～7次乙酸乙酯萃取利用纯乙酸乙酯进行；第二乙酯相的第1～4水洗利用上一批次三氯蔗糖粗品的制备过程中第二乙酯相的第2～5次水洗得到的水相，第二乙酯相的第5次水洗利用纯水进行；循环利用17次得到的三氯蔗糖粗品的纯度及收率数据如表8所示：
表8三氯蔗糖粗品纯度及收率
Figure PCTCN2022126186-appb-000006
注：理论最大收率117.45％。
实施例5
按照实施例1的方法制备三氯蔗糖粗品，与实施例1的区别在于：
步骤(1)中，使用的第一溶液的主要成分如表9所示，单次萃取用乙酸乙酯体积为500mL，萃取温度为60℃，萃取时间为10min，水相重复上述萃取步骤6次，第一水相中三氯蔗糖-6-乙酸酯含量为0.03g/L；
表9第一溶液成分表
组分 含量
三氯蔗糖-6-乙酸酯 80.0g/L
三氯蔗糖双酯 7.1g/L
四氯蔗糖-6-乙酸酯 8.5g/L
NH 4Cl 131.9g/L
其他有机杂质 69.2g/L
水 73.5％
步骤(2)中，在60℃、-0.09MPa条件下浓干，三氯蔗糖-6-乙酸酯水溶液(700mL，乙酸乙酯含量为0.50g/L)；
步骤(3)中，降温至0℃，碱解温度为5℃，碱解pH＝13.0，碱解时间为3h，第二水相(770mL，三氯蔗糖-6-乙酸酯含量为0.05g/L)；
步骤(4)中，乙酸乙酯单次加入量1540mL，萃取7次，第二乙酯相体积为3360mL，第3～7次乙酸乙酯萃取得到的乙酯相依次作为下一批次三氯蔗糖粗品的制备过程中第二水相的第1～5次乙酸乙酯萃取，水洗次数为5次，第二乙酯相的第2～5次水洗得到的水相依次下一批次三氯蔗糖粗品的制备过程中第二乙酯相的第1～4水洗，单次水洗用水500mL，在60℃、-0.1MPa条件下浓干，浓干过程中乙酸乙酯加入次数为3次，单次加入乙酸乙酯量为700mL，Bx为60％；
步骤(5)中，结晶温度为45℃，结晶时间为24h，第五乙酯相体积为360mL，水洗次数为7次，单次水洗用水量为150mL，第六乙酯相中三氯蔗糖含量为0.08g/L；
步骤(6)中，第二水相的第1～5次乙酸乙酯萃取利用上一批次三氯蔗糖粗品的制备过程中第二水相的第3～7次乙酸乙酯萃取得到的乙酯相，第二水相的第6～7次乙酸乙酯萃取利用纯乙酸乙酯进行；第二乙酯相的第1～4水洗利用上一批次三氯蔗糖粗品的制备过程中第二乙酯相的第2～5次水洗得到的水相，第二乙酯相的第5次水洗利用纯水进行；循环利用 17次得到的三氯蔗糖粗品的纯度及收率数据如表10所示：
表10三氯蔗糖粗品纯度及收率
Figure PCTCN2022126186-appb-000007
注：理论最大收率117.95％。
实施例6
按照实施例1的方法制备三氯蔗糖粗品，与实施例1的区别在于：
步骤(1)中，使用的第一溶液的主要成分如表11所示，单次萃取用乙酸乙酯体积为500mL，萃取温度为45℃，萃取时间为20min，水相重复上述萃取步骤7次，第一水相中三氯蔗糖-6-乙酸酯含量为0.07g/L；
表11第一溶液成分表
组分 含量
三氯蔗糖-6-乙酸酯 76.1g/L
三氯蔗糖双酯 6.7g/L
四氯蔗糖-6-乙酸酯 8.3g/L
NH 4Cl 131.4g/L
其他有机杂质 60.2g/L
水 74.8％
步骤(2)中，在80℃、-0.08MPa条件下浓干，三氯蔗糖-6-乙酸酯水溶液(690mL，乙酸乙酯含量为0.32g/L)；
步骤(3)中，降温至5℃，碱解温度为5℃，碱解pH＝12.8，碱解时间为4h，中和至pH＝6.9，热过滤温度为55℃，第二水相(810mL，三氯蔗糖-6-乙酸酯含量为0.02g/L)；
步骤(4)中，乙酸乙酯单次加入量2000mL，萃取5次，第二乙酯相体积为4300mL，第3～5次乙酸乙酯萃取得到的乙酯相依次作为下一批次三氯蔗糖粗品的制备过程中第二水相的第1～3次乙酸乙酯萃取，水洗次数为5次，单次水洗用水500mL，第二乙酯相的第2～5次水洗得到的水相依次下一批次三氯蔗糖粗品的制备过程中第二乙酯相的第1～4水洗，在65℃、-0.09MPa条件下浓干，浓干过程中乙酸乙酯加入次数为4次，单次加入乙酸乙酯量为900mL，Bx为57％；
步骤(5)中，结晶温度为50℃，结晶时间为26h，第五乙酯相体积为370mL，水洗次数为6次，单次水洗用水量为180mL，第六乙酯相中三氯蔗糖含量为0.07g/L；
步骤(6)中，第二水相的第1～3次乙酸乙酯萃取利用上一批次三氯蔗糖粗品的制备过程中第二水相的第3～5次乙酸乙酯萃取得到的乙酯相，第二水相的第4～5次乙酸乙酯萃取利用纯乙酸乙酯进行；第二乙酯相的第1～4水洗利用上一批次三氯蔗糖粗品的制备过程中第二乙酯相的第2～5次水洗得到的水相，第二乙酯相的第5次水洗利用纯水进行；循环利用17次得到的三氯蔗糖粗品的纯度及收率数据如表12所示：
表12三氯蔗糖粗品纯度及收率
Figure PCTCN2022126186-appb-000008
Figure PCTCN2022126186-appb-000009
注：理论最大收率118.15％。
实施例7
按照实施例1的方法制备三氯蔗糖粗品，与实施例1的区别在于：
步骤(1)中，使用的第一溶液的主要成分如表13所示，单次萃取用乙酸乙酯体积为200mL，萃取温度为60℃，萃取时间为15min，水相重复上述萃取步骤7次，第一水相中三氯蔗糖-6-乙酸酯含量为0.06g/L；
表13第一溶液成分表
组分 含量
三氯蔗糖-6-乙酸酯 61.2g/L
三氯蔗糖双酯 4.7g/L
四氯蔗糖-6-乙酸酯 5.5g/L
NH 4Cl 97.3g/L
其他有机杂质 34.2g/L
水 81.9％
步骤(2)中，在70℃、-0.08MPa条件下浓干，三氯蔗糖-6-乙酸酯水溶液(630mL，乙酸乙酯含量为0.22g/L)；
步骤(3)中，降温至3℃，碱解温度为3℃，碱解pH＝12.4，碱解时间为3.5h，中和至pH＝6.8，热过滤温度为50℃，第二水相(670mL，三氯蔗糖-6-乙酸酯含量为0.05g/L)；
步骤(4)中，乙酸乙酯单次加入量1400mL，第二乙酯相体积为3100mL，水洗次数为5次，单次水洗用水700mL，第二乙酯相的第2～5次水洗得到的水相依次下一批次三氯蔗糖粗品的制备过程中第二乙酯相的第1～4水洗，在65℃、-0.09MPa条件下浓干，浓干过程中乙酸乙酯加入次数为2次，单次加入乙酸乙酯量为800mL，Bx为48％；
步骤(5)中，结晶温度为40℃，结晶时间为34h，第五乙酯相体积为400mL，水洗次数为5次，单次水洗用水量为200mL，第六乙酯相中三氯蔗糖含量为0.04g/L；
步骤(6)中，第二乙酯相的第1～4水洗利用上一批次三氯蔗糖粗品 的制备过程中第二乙酯相的第2～5次水洗得到的水相，第二乙酯相的第5次水洗利用纯水进行；循环利用17次得到的三氯蔗糖粗品的纯度及收率数据如表14所示：
表14三氯蔗糖粗品纯度及收率
Figure PCTCN2022126186-appb-000010
注：理论最大收率115.34％。
实施例8
按照实施例1的方法制备三氯蔗糖粗品，与实施例1的区别在于：
步骤(1)中，使用的第一溶液的主要成分如表15所示，单次萃取用乙酸乙酯体积为300mL，萃取温度为40℃，萃取时间为20min，水相重复上述萃取步骤5次，第一水相中三氯蔗糖-6-乙酸酯含量为0.09g/L；
表15第一溶液成分表
组分 含量
三氯蔗糖-6-乙酸酯 57.7g/L
三氯蔗糖双酯 5.1g/L
四氯蔗糖-6-乙酸酯 6.4g/L
NH 4Cl 89.9g/L
其他有机杂质 33.1g/L
水 82.8％
步骤(2)中，在70℃、-0.09MPa条件下浓干，三氯蔗糖-6-乙酸酯水溶液(600mL，乙酸乙酯含量为0.48g/L)；
步骤(3)中，降温至1℃，碱解温度为1℃，碱解pH＝12.0，碱解时间为4.5h，中和至pH＝7，热过滤温度为45℃，第二水相(640mL，三氯蔗糖-6-乙酸酯含量为0.04g/L)；
步骤(4)中，乙酸乙酯单次加入量1000mL，萃取7次，第二乙酯相体积为2200mL，第3～7次乙酸乙酯萃取得到的乙酯相依次作为下一批次三氯蔗糖粗品的制备过程中第二水相的第1～5次乙酸乙酯萃取，水洗次数为5次，单次水洗用水300mL，第二乙酯相的第2～5次水洗得到的水相依次下一批次三氯蔗糖粗品的制备过程中第二乙酯相的第1～4水洗，在80℃、-0.08MPa条件下浓干，浓干过程中乙酸乙酯加入次数为2次，单次加入乙酸乙酯量为800mL，Bx为45％；
步骤(5)中，结晶温度为40℃，结晶时间为32h，第五乙酯相体积为410mL，水洗次数为5次，单次水洗用水量为220mL，第六乙酯相中三氯蔗糖含量为0.02g/L；
步骤(6)中，第二水相的第1～5次乙酸乙酯萃取利用上一批次三氯蔗糖粗品的制备过程中第二水相的第3～7次乙酸乙酯萃取得到的乙酯相，第二水相的第6～7次乙酸乙酯萃取利用纯乙酸乙酯进行；第二乙酯相的第1～4水洗利用上一批次三氯蔗糖粗品的制备过程中第二乙酯相的第2～5次水洗得到的水相，第二乙酯相的第5次水洗利用纯水进行；循环利用17次得到的三氯蔗糖粗品的纯度及收率数据如表16所示：
表16三氯蔗糖粗品纯度及收率
Figure PCTCN2022126186-appb-000011
Figure PCTCN2022126186-appb-000012
注：理论最大收率118.35％。
套用的过程中使三氯蔗糖和杂质在乙酯相中处于一种平衡状态，即通过控制以下条件使得三氯蔗糖收率在105％以上：(1)碱解后的第二水相中的三氯蔗糖-6-乙酸酯含量达到指定标准；(2)第一水相和第三水相中的残糖达到规定的标准；(3)结晶时，乙酸乙酯相中的水含量达到指定标准；(4)第六乙酯相中的残糖需要达到制定标准；(5)结晶条件稳定。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而造成的损失。而且，第四水相和第五水相中含有残留的三氯蔗糖得到充分利用，提高了三氯蔗糖的收率。
从以上实施例可以发现，在初始的几个操作流程中，例如第1～2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％，其原因是第一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，且本发明以第一水溶液为原料，无需对三氯蔗糖-6-乙酸酯粗品进行提纯，工艺更加简单，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三氯蔗糖-6-乙酸酯的损耗，本发明提供的方法具有极为明显的优势。
本发明将本生产流程中特定步骤的水相(第四水相和第五水相)存储， 在下一生产流程中继续用于除去碱解反应体系中的乙酸乙酯，能够减少副产物乙酸和乙醇的生成，从而提高三氯蔗糖的纯度；同时，通过三氯蔗糖在生产流程内循环没有流出生产流程外，使得第四水相和第五水相中含有的三氯蔗糖能够得到充分利用，大幅减少了三氯蔗糖的损失，大大提高了三氯蔗糖的整体收率。本发明的结晶工艺相较现有结晶工艺三氯蔗糖的本工序的收率不高(结晶产物与结晶原料的比值)，但是三氯蔗糖粗品纯净度高；尽管结晶工序收率不高，但是由于第四水相和第五水相的循环使用，本生产流程引入了上一流程的第四水相和第五水相(本流程未结晶的三氯蔗糖会进入下一生产流程内)，因此从全生产流程来看，获得的三氯蔗糖粗品产量与理论产量(以投入的原料计算理论产量)的比值明显高于现有生产工艺。采用本发明提供的方法以，三氯蔗糖粗品的纯度提高，后续处理的难度降低，三氯蔗糖总体原料的整体收率提高。本发明提供的方法，碱解步骤使用碱金属强氧化物，替代传统的具有较高危害性的甲醇钠/甲醇反应体系，安全环保。在第四水相和第五水相的循环使用过程中将体系中的脂溶性焦糖类杂质引入乙酸乙酯中，一方面降低了除杂的难度以及废弃物处理难度，另外一方面增加三氯蔗糖在乙酸乙酯中的溶解度，使得结晶过程中三氯蔗糖得到充分富集和结晶，提高了收率。
综上所述，本发明提供的方法采用碱金属氢氧化物、水体系中进行碱解，乙酸乙酯/水双体系套用(第四水相和第五水相回用于溶解所述第一乙酯相浓缩物)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 (14)

  1. 一种利用水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)将原料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，得到第一乙酯相浓缩物；所述原料液为包括三氯蔗糖-6-乙酸酯、三氯蔗糖双酯和四氯蔗糖-6-乙酸酯的水溶液；
    (2)将所述第一乙酯相浓缩物与水混合溶解，进行浓缩，得到三氯蔗糖-6-乙酸酯水溶液；
    (3)将所述三氯蔗糖-6-乙酸酯水溶液与碱金属氢氧化物混合，进行碱解反应，将得到的反应液进行中和后热过滤，得到第二水相；
    (4)将所述第二水相进行乙酸乙酯萃取，分别得到第二乙酯相和第三水相；
    (5)将所述第二乙酯相进行水洗，分别得到第四水相和第三乙酯相；所述第四水相回用于步骤(2)中用于溶解所述第一乙酯相浓缩物；
    (6)将所述第三乙酯相与乙酸乙酯混合，进行共沸除水，得到第三乙酯相浓缩物；将所述第三乙酯相浓缩物与乙酸乙酯混合，得到第四乙酯相；
    (7)将所述第四乙酯相进行结晶，分别得到三氯蔗糖粗品和第五乙酯相；
    (8)将所述第五乙酯相进行水洗，分别得到第五水相和第六乙酯相；所述第五水相回用于步骤(2)用于溶解所述第一乙酯相浓缩物。
  2. 根据权利要求1所述的方法，其特征在于，步骤(1)中，所述乙酸乙酯萃取的温度为40～60℃，萃取次数为5～8次；所述原料液与单次乙酸乙酯萃取用乙酸乙酯的体积比为1：0.2～0.4。
  3. 根据权利要求1或2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(2)中，所述三氯蔗糖-6-乙酸酯水溶液中乙酸乙酯的含量＜0.5g/L。
  5. 根据权利要求1所述的方法，其特征在于，步骤(3)中，所述碱解反应的pH值为11～13，温度为0～10℃，时间3～6h。
  6. 根据权利要求1所述的方法，其特征在于，步骤(3)中，所述热过滤的温度为45～70℃。
  7. 根据权利要求1所述的方法，其特征在于，步骤(4)中，所述乙酸乙酯萃取的次数为4～7次；所述第二水相与乙酸乙酯萃取单次用乙酸乙酯的体积比为1：1～3；
    将第1～2次乙酸乙酯萃取得到的乙酯相合并作为第二乙酯相；
    将第3～7次乙酸乙酯萃取得到的乙酯相用于下一批次三氯蔗糖粗品制备过程中所述第二水相的乙酸乙酯萃取。
  8. 根据权利要求1或7所述的方法，其特征在于，步骤(4)中，所述第三水相中三氯蔗糖含量<0.5g/L。
  9. 根据权利要求1所述的方法，其特征在于，步骤(5)中，所述水洗的次数为3～5次；所述第二乙酯相与水洗的单次用水的体积比为1：0.1～0.3；
    将第1次水洗得到的水相作为第四水相；
    将第2～5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。
  10. 根据权利要求1或9所述的方法，其特征在于，步骤(5)中，所述第三水相中的三氯蔗糖的含量＜0.5g/L。
  11. 根据权利要求1所述的方法，其特征在于，步骤(6)中，所述第三乙酯相浓缩液的水含量＜0.5wt％。
  12. 根据权利要求1或11所述的方法，其特征在于，步骤(6)中，所述第四乙酯相的糖度为40～60％。
  13. 根据权利要求1所述的方法，其特征在于，步骤(7)中，所述结晶的温度为40～60℃，时间12～35h。
  14. 根据权利要求1所述的方法，其特征在于，所述第六乙酯相中三氯蔗糖含量<0.1g/L。
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