WO2024082154A1 - 一种利用改进的水解体系制备三氯蔗糖粗品的方法 - Google Patents

一种利用改进的水解体系制备三氯蔗糖粗品的方法 Download PDF

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WO2024082154A1
WO2024082154A1 PCT/CN2022/126043 CN2022126043W WO2024082154A1 WO 2024082154 A1 WO2024082154 A1 WO 2024082154A1 CN 2022126043 W CN2022126043 W CN 2022126043W WO 2024082154 A1 WO2024082154 A1 WO 2024082154A1
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sucralose
ethyl ester
phase
aqueous phase
acetate
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PCT/CN2022/126043
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English (en)
French (fr)
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陈永乐
郭思雨
余瑶
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 CN202280004540.XA priority Critical patent/CN116134043A/zh
Priority to PCT/CN2022/126043 priority patent/WO2024082154A1/zh
Publication of WO2024082154A1 publication Critical patent/WO2024082154A1/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    • C07H5/00—Compounds containing saccharide radicals in which the hetero bonds to oxygen have been replaced by the same number of hetero bonds to halogen, nitrogen, sulfur, selenium, or tellurium
    • C07H5/02—Compounds containing saccharide radicals in which the hetero bonds to oxygen have been replaced by the same number of hetero bonds to halogen, nitrogen, sulfur, selenium, or tellurium to halogen

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  • the invention relates to the technical field of fine chemicals, and in particular to a method for preparing crude sucralose by utilizing an improved 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 involves the following five steps: using sucrose as raw material, esterification, chlorination, alcoholysis, crystallization and separation and purification are carried out in sequence, among which the main process section that affects the total yield of sucralose is chlorination.
  • the mainstream process of chlorination is phosgene chlorination or thionyl chloride chlorination. Both chlorination processes involve high-temperature reactions.
  • Sucralose which is heat-sensitive, will produce a large amount of by-products during the chlorination process.
  • high-purity more than 99%
  • 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 an improved 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 an improved hydrolysis system, comprising the following steps:
  • the first aqueous solution is an aqueous solution comprising sucralose-6-acetate, sucralose diester and tetrachlorosucrose-6-acetate;
  • the first aqueous solution is an aqueous solution comprising sucralose-6-acetate, sucralose diester and tetrachlorosucrose-6-acetate;
  • step (2) washing the first ethyl ester phase with water to obtain a third aqueous phase and a second ethyl ester phase respectively; the third aqueous phase is reused in step (2), wherein the third aqueous phase is mixed and concentrated with the first aqueous solution during the reuse, and then mixed with an alkali metal hydroxide;
  • step (3) washing the fourth ethyl ester phase with water to obtain a fourth aqueous phase and a fifth ethyl ester phase respectively; the fourth aqueous phase is reused in step (2), wherein the fourth aqueous phase is mixed and concentrated with the first aqueous solution during the reuse, and then mixed with an alkali metal hydroxide.
  • the pH value of the alkaline hydrolysis reaction is 12 to 13, the temperature is 5 to 15° C., and the time is 4 to 7 hours.
  • the temperature of the hot filtration is 60-80°C.
  • the temperature of the ethyl acetate extraction is 40-60°C; the number of ethyl acetate extractions is 5-7 times; the volume ratio of the first aqueous phase to the ethyl acetate used in the single ethyl acetate extraction is 1:1-3;
  • the ethyl ester phases obtained from the first and second ethyl acetate extractions are combined as the first 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 first aqueous phase in the preparation process of the next batch of crude sucralose.
  • the content of sucralose in the second aqueous phase is less than 0.5 g/L.
  • the number of water washings is 4 to 6 times; the volume ratio of the first ethyl ester phase to the single water used for the water washing is 1:0.1 to 0.3;
  • the aqueous phases obtained from the first and second water washings are combined as the third aqueous phase;
  • the aqueous phase obtained from the 3rd to 6th water washing is used for washing the first ethyl ester phase in the preparation process of the next batch of crude sucralose.
  • the content of sucralose in the second aqueous phase is less than 0.5 g/L.
  • the water content of the second ethyl ester phase concentrate is less than 0.5 wt%.
  • the sugar content of the third ethyl ester phase is 45-60 wt %.
  • the crystallization temperature is 40 to 60° C. and the time is 24 to 36 hours.
  • the sucralose content in the fifth ethyl ester phase is less than 0.1 g/L.
  • the present invention provides a method for preparing crude sucralose using an improved hydrolysis system.
  • a first aqueous solution (containing sucralose-6-acetate, sucralose diester and tetrachlorosucrose-6-acetate) is directly subjected to alkaline hydrolysis in an alkali metal hydroxide-water system.
  • Sucralose-6-acetate, sucralose diester and tetrachlorosucrose-6-acetate are all subjected to alkaline hydrolysis in the presence of a strong alkaline aqueous solution to generate corresponding sucralose and tetrachlorosucrose.
  • Tetrachlorosucrose 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 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.
  • sucralose-6-acetate and impurities sucralose diester and tetrachlorosucrose-6-acetate
  • 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 and water, and can realize mutual application of the dual systems to extract and remove impurities, enrich sucralose, so that sucralose can be crystallized in ethyl acetate in large quantities, and the sucralose can be recovered by repeated application, thereby avoiding the loss of sucralose and greatly improving the overall yield of sucralose.
  • sucralose-6-acetate using sucrose-6-acetate as raw material
  • ammonia water is used for neutralization after chlorination, which will produce a large amount of ammonium chloride, and ethyl acetate extraction is required before alkaline hydrolysis to separate ammonium chloride (aqueous phase) and sucralose-6-acetate (ethyl acetate phase).
  • the present invention uses alkali metal hydroxide neutralization instead of traditional ammonia water neutralization, and there is no need to perform ethyl acetate extraction to separate ammonium chloride and sucralose-6-acetate first, and alkaline hydrolysis can be directly performed, reducing the amount of ethyl acetate solvent, while avoiding the decomposition of ammonium chloride to produce ammonia gas during alkaline hydrolysis, and the salts produced by neutralization are all chloride salts, which are removed in the subsequent ethyl acetate extraction process, reducing the number and amount of salt wastewater discharge, and relieving the subsequent environmental protection treatment pressure.
  • FIG. 1 is a process flow chart of preparing crude sucralose using an improved hydrolysis system in Example 1.
  • the present invention provides a method for preparing crude sucralose by using an improved hydrolysis system, comprising the following steps:
  • the first aqueous solution is an aqueous solution comprising sucralose-6-acetate, sucralose diester and tetrachlorosucrose-6-acetate;
  • the first aqueous solution is an aqueous solution comprising sucralose-6-acetate, sucralose diester and tetrachlorosucrose-6-acetate;
  • step (2) washing the first ethyl ester phase with water to obtain a third aqueous phase and a second ethyl ester phase respectively; the third aqueous phase is reused in step (2), wherein the third aqueous phase is mixed and concentrated with the first aqueous solution during the reuse, and then mixed with an alkali metal hydroxide;
  • step (3) washing the fourth ethyl ester phase with water to obtain a fourth aqueous phase and a fifth ethyl ester phase respectively; the fourth aqueous phase is reused in step (2), wherein the fourth aqueous phase is mixed and concentrated with the first aqueous solution during the reuse, and then mixed with an alkali metal hydroxide.
  • the present invention sequentially chlorinates, neutralizes with alkali metal hydroxide, concentrates and dissolves in water a solution containing sucrose-6-acetate to obtain a first aqueous solution;
  • the first aqueous solution is an aqueous solution comprising sucralose-6-acetate, sucralose diester and tetrachlorosucrose-6-acetate.
  • the solution containing sucrose-6-acetate is preferably prepared from sucrose.
  • sucrose is used as a raw material
  • N,N-dimethylformamide (DMF) is used as a solvent
  • organic tin is used as a catalyst
  • acetic anhydride is used as an acylating agent to prepare the solution containing sucrose-6-acetate.
  • the present invention has no particular limitation on the preparation method of the solution containing sucrose-6-acetate, and a preparation method well known to those skilled in the art can be used.
  • the alkali metal hydroxide used for neutralization of the alkali metal hydroxide preferably includes sodium hydroxide, and 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%.
  • sucralose-6-acetate In the traditional process of preparing sucralose-6-acetate from sucrose-6-acetate as a raw material, ammonia water is used for neutralization after chlorination, which will produce a large amount of ammonium chloride, and ethyl acetate extraction is required before alkaline hydrolysis to separate ammonium chloride (in the aqueous phase) and sucralose-6-acetate (in the ethyl acetate phase).
  • the present invention uses alkali metal hydroxide neutralization to replace the traditional ammonia water neutralization, and there is no need to perform ethyl acetate extraction to separate ammonium chloride and sucralose-6-acetate first, and alkaline hydrolysis is directly performed, which reduces the amount of ethyl acetate solvent, and avoids the decomposition of ammonium chloride to produce ammonia gas during alkaline hydrolysis.
  • the salts produced by neutralization are all chloride salts, which are removed in the subsequent ethyl acetate extraction process, reducing the number and amount of salt wastewater discharges and relieving the subsequent environmental protection treatment pressure.
  • the present invention uses alkali metal hydroxide for neutralization, and the third and fourth aqueous phases generated in the preparation process of crude sucralose can be used as azeotropic agents, avoiding the use of salt-free water and reducing production costs.
  • the present invention uses alkali metal hydroxide instead of traditional ammonia water for neutralization, which will lead to an increase in the total amount of chloride salts in the first aqueous solution, increase the difficulty of extraction, and the chloride salt concentration in the second aqueous phase is too high and salting out is easy to occur.
  • the present invention can avoid the phenomenon of salting out in the second aqueous phase due to the high chloride salt concentration by controlling the number of extractions of ethyl acetate; the present invention balances the impurities removed by omitting the ethyl acetate extraction step before alkaline hydrolysis, and balances the impurities not removed by omitting the ethyl acetate extraction before alkaline hydrolysis in the fourth aqueous phase for recycling by controlling the number of water washings.
  • the increase of water-soluble impurities in the system affects the crystallization of crude sucralose, but only affects the crystallization time, and has little effect on the yield of sucralose.
  • the present invention uses alkali metal hydroxide instead of traditional ammonia water for neutralization, which leads to an increase in the total amount of chloride salts in the first aqueous solution, it does not affect the yield of sucralose and the overall preparation process, and can significantly reduce the amount of ethyl acetate and the discharge of high-salt wastewater, and achieve a higher yield of sucralose.
  • the content of sucralose-6-acetate is preferably 50-80 g/L, more preferably 55-75 g/L;
  • the mass ratio of sucralose-6-acetate, sucralose diester and tetrachlorosucrose-6-acetate in the first aqueous solution is preferably 1: 0.06-0.15: 0.06-0.15, more preferably 1: 0.08-0.1: 0.09-0.13;
  • the first aqueous solution preferably also includes alkali metal chloride and organic impurities, the concentration of the alkali metal chloride is preferably 80-160 g/L, more preferably 80-120 g/L, the alkali metal chloride preferably includes NaCl and/or KCl, more preferably NaCl;
  • the concentration of the organic impurities is preferably 25-70 g/L, more preferably 29-50 g/L.
  • the present invention has no particular limitation on the chlorination, concentration and water dissolution.
  • the first aqueous solution of the above composition can be obtained by using a method for preparing sucralose-6-acetate using sucrose-6-acetate as a raw material, which is well known to those skilled in the art.
  • the present invention mixes the first 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 first aqueous phase.
  • the alkali metal hydroxide preferably includes sodium hydroxide and/or potassium hydroxide, more preferably sodium hydroxide.
  • the present invention uses sodium hydroxide as a reagent for alkaline hydrolysis reaction, and the production cost is low; 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 12-13, and the pH value is more preferably 12.2-12.8, and further preferably 12.5; the temperature of the alkaline hydrolysis reaction is preferably 5-15°C, more preferably 8-12°C, and further preferably 10°C; the time of the alkaline hydrolysis reaction is preferably 4-7h, more preferably 4.5-6.5h, and further preferably
  • the present invention performs alkaline hydrolysis reaction under the above conditions, so that sucralose diester can be hydrolyzed to generate sucralose, and sucralose-6-acetate can be dechlorinated and hydrolyzed to generate sucralose, and the generation of by-products due to too high pH value or too high temperature of the alkaline hydrolysis reaction can be avoided.
  • 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 60-80° C., more preferably 65-75° C., and further preferably 70° C.
  • the reaction liquid obtained by the alkaline hydrolysis reaction is heated to 60-80° C. for neutralization, 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 at the same time, it can also avoid the sucralose from being caramelized due to excessive temperature.
  • the present invention extracts the first aqueous phase with ethyl acetate to obtain a first ethyl ester phase and a second aqueous phase, respectively.
  • the temperature of the ethyl acetate extraction is preferably 40-60°C, more preferably 45-55°C, and further preferably 50°C; the number of ethyl acetate extractions is preferably 5-7 times; the time of a single ethyl acetate extraction is preferably 10-30 min, more preferably 15-20 min; the volume ratio of the first aqueous phase to the ethyl acetate used in a single ethyl acetate extraction is preferably 1:1-3, more preferably 1:1.5-2.5; in the present invention, the ethyl ester phases obtained by the first to second ethyl acetate extractions are preferably combined as the first ethyl ester phase; the ethyl ester phases obtained by the third to seventh ethyl acetate extractions are preferably used for the ethyl acetate extraction of the first aqueous phase in the preparation process of the next batch of crude sucralose Specifically, the ethyl a
  • the content of sucralose in the second aqueous phase is preferably ⁇ 0.5 g/L.
  • the temperature of the ethyl acetate extraction is preferably 40 to 60° C., more preferably 45 to 55° C.
  • the single ethyl acetate extraction time is preferably 10 to 30 min, more preferably 15 to 25 min, and the ethyl acetate extraction is preferably carried out under stirring conditions.
  • the present invention washes the first ethyl ester phase with water to obtain a third aqueous phase and a second ethyl ester phase respectively; the third aqueous phase is reused in step (2), and during the reuse, the third aqueous phase is mixed and concentrated with the first aqueous solution, and then mixed with an alkali metal hydroxide.
  • the number of water washings is preferably 4 to 6 times; the volume ratio of the first ethyl ester phase to the single water used for water washing is preferably 1:0.1 to 0.3, more preferably 1:0.15 to 0.25; in the present invention, the aqueous phases obtained from the first to second water washings are preferably combined as the third aqueous phase, and the aqueous phases obtained from the third to sixth water washings are preferably used for the water washing of the first ethyl ester phase in the preparation process of the next batch of crude sucralose.
  • the aqueous phase obtained from the third water washing is used for the first water washing of the first ethyl ester phase in the preparation process of the next batch of crude sucralose
  • the aqueous phase obtained from the fourth water washing is used for the first water washing of the first ethyl ester phase in the preparation process of the next batch of crude sucralose.
  • the obtained aqueous phase is used for the second water washing of the first ethyl ester phase in the preparation process of the next batch of crude sucralose
  • the aqueous phase obtained after the fifth water washing is used for the third water washing of the first ethyl ester phase in the preparation process of the next batch of crude sucrose
  • the aqueous phase obtained after the sixth water washing is used for the fourth water washing of the first ethyl ester phase in the preparation process of the next batch of crude sucrose (i.e., the aqueous phases obtained after the third to sixth water washings are used sequentially for the first to fourth water washings of the first ethyl ester phase in the preparation process of the next batch of crude sucralose).
  • the fifth to sixth water washings of the first ethyl ester phase of the next batch of crude sucralose are preferably carried out with pure water.
  • the present invention mixes the second ethyl ester phase with ethyl acetate and performs azeotropic dehydration to obtain a second ethyl ester phase concentrate; and mixes the second ethyl ester phase concentrate with ethyl acetate to obtain a third 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, 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 preferably 60 to 80°C
  • the concentration degree is preferably -0.1 to -0.08 MPa (gauge pressure).
  • concentration time 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 water content of the second ethyl ester phase concentrate is less than 0.5wt%.
  • the present invention has no special limitation on the amount of ethyl acetate, and the sugar content (Bx) of the third ethyl ester phase is 45 to 60%, and the sugar content is more preferably 50 to 55%.
  • the present invention crystallizes the third ethyl ester phase to obtain crude sucralose and a fourth ethyl ester phase, respectively.
  • the crystallization temperature is preferably 40-60°C, more preferably 45-55°C; the crystallization time is preferably 24-36h, more preferably 25-30h.
  • the solubility of sucralose in ethyl acetate is low.
  • the present invention can significantly increase the solubility of sucralose in ethyl acetate by introducing fat-soluble caramel impurities in the system into ethyl acetate during the recycling of the third aqueous phase and the fourth aqueous phase, and adopt 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 a fourth ethyl ester phase, respectively.
  • the solid-liquid separation preferably comprises filtration or suction filtration.
  • the present invention washes the fourth ethyl ester phase with water to obtain a fourth aqueous phase and a fifth ethyl ester phase respectively; the fourth aqueous phase is reused in step (2), and during the reuse, the fourth aqueous phase is mixed and concentrated with the first aqueous solution, and then mixed with an alkali metal hydroxide.
  • the third aqueous phase and the fourth aqueous phase are both recycled in step (2), during the recycling, the third aqueous phase, the fourth aqueous phase and the first aqueous solution are mixed and concentrated to obtain a first aqueous concentrate (a concentrate of the first aqueous solution, the third aqueous phase and the fourth aqueous phase), and then the first aqueous concentrate is mixed with an alkali metal hydroxide; the volume ratio of the first aqueous solution to the first aqueous concentrate is preferably 1:0.5-1, more preferably 1:0.6-1.
  • the present invention has no special limitation on the number of times of water washing, and the sucralose content in the fifth ethyl ester phase obtained by the last water washing is ⁇ 0.1g/L, specifically 4 to 8 times.
  • the volume ratio of the fourth ethyl ester phase to the single water used for water washing is preferably 1:0.5 to 1, and more preferably 1:0.6 to 0.8.
  • the fifth ethyl ester phase is preferably concentrated to obtain recovered ethyl acetate and sugar residue, and the sugar residue is preferably treated as solid waste. After crystallization is completed, there are more fat-soluble impurities in the fourth ethyl ester phase, and the solubility of sucralose in water is high.
  • the present invention adopts a water washing method to recover the uncrystallized sucralose into the fourth aqueous phase, and recycle the fourth aqueous phase, which can improve the recovery rate of sucralose, and at the same time, the fat-soluble impurities in the sucralose crystals can be removed to improve its purity.
  • 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 crude sucralose is prepared using the process flow chart shown in FIG1 , and the specific steps are as follows:
  • sucrose as a raw material, DMF as a solvent, organotin as a catalyst, and acetic anhydride as an acylating agent
  • a solution containing sucrose-6-acetate is prepared; then the obtained solution containing sucrose-6-acetate is sequentially chlorinated, neutralized with a sodium hydroxide aqueous solution, vacuum concentrated to dryness, and dissolved in water to obtain a first aqueous solution.
  • the composition of the first aqueous solution is shown in Table 1:
  • step (2) (4) adding 550 mL of water to the first ethyl ester phase for washing 6 times, wherein the aqueous phase obtained after the first and second washings is the third aqueous phase, and the third aqueous phase is used in step (2) to be mixed with the first aqueous solution and then concentrated; the aqueous phases obtained after the third to sixth washings are used in sequence for the first to fourth washings of the first ethyl ester phase in the preparation process of the next batch of crude sucralose, and the ester phase obtained after the washings is the second ethyl ester phase.
  • the second ethyl ester phase was concentrated at 70° C. and ⁇ 0.09 MPa (gauge pressure). During the concentration process, ethyl acetate was added (3 times, 300 mL each time) for azeotropic dehydration. Ethyl acetate was added to the obtained second ethyl ester phase concentrate (water content ⁇ 0.5 wt%) to adjust the sugar content to Bx of 55%, thereby obtaining a third ethyl ester phase.
  • the fourth ethyl ester phase is washed with water for 6 times (each time with a water dosage of 210 mL), and the ester phase after washing is the sixth ester phase (sucralose content: 0.03 g/L).
  • the sixth ester phase is concentrated and dried to obtain recovered ethyl acetate and sugar residue (solid waste treatment) respectively; the aqueous phases are combined as the fourth aqueous phase, and the fourth aqueous phase is used in step (2) to be mixed with the first aqueous solution and then concentrated.
  • step (3) the ester phase obtained by the 3rd to 6th extraction of the first aqueous phase in the preparation process of the previous batch of crude sucralose is successively used for the 1st to 4th extraction of the first aqueous phase, and pure ethyl acetate is used for 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 116.54%.
  • sucralose and impurities are in a state of equilibrium in the ethyl ester phase, that is, the yield of sucralose is stabilized at more than 105% under the following conditions: (1) the content of sucralose-6-acetate 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 fifth ethyl ester phase needs to reach the specified standard; and (5) the crystallization conditions are stable.
  • the yield is calculated by converting all sucralose-6-acetate into sucralose, and the yield exceeds 100%.
  • the first aqueous solution 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 yield of sucralose provided by the method provided by the present invention is significantly improved.
  • 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, avoiding the loss of sucralose-6-acetate caused by the need to purify sucralose-6-acetate before alkaline hydrolysis in the traditional process.
  • the method provided by the present invention has extremely obvious advantages.
  • the residual sucralose contained in the third aqueous phase and the fourth aqueous phase is fully utilized, thereby improving the yield of sucralose.
  • the method provided by the present invention does not extract the first aqueous solution with ethyl acetate, but uses an alkali metal hydroxide and water system for alkaline hydrolysis, and uses an ethyl acetate/water dual system (the third aqueous phase and the fourth aqueous phase are reused in step (2) to be mixed and concentrated with the first aqueous solution, the ethyl ester phase obtained by the 3rd to 7th ethyl acetate extraction of the first aqueous phase is sequentially used for the 1st to 5th ethyl acetate extraction of the first aqueous phase in the next batch of sucralose crude product preparation process, and the aqueous phase obtained by the 3rd to 6th water washing of the first ethyl ester phase is sequentially used for the 1st to 4th water washing of the first ethyl ester phase in the next batch of sucralose crude product preparation process) to extract and remove impurities, sucra

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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-乙酸酯的水溶液为第一水溶液，在碱金属氢氧化物和水体系中进行碱解，能够将第一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。

Description

一种利用改进的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，特别涉及一种利用改进的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：以蔗糖为原料，依次进行酯化、氯化、醇解、结晶和分离提纯，其中，影响三氯蔗糖总收率的主要工段为氯化。氯化的主流工艺为光气氯化或氯化亚砜氯化，这两种氯化工艺均涉及高温反应，具有热敏性的三氯蔗糖在氯化过程中会产生大量的副产物。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改进的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改进的水解体系制备三氯蔗糖粗品的方法，包括以下步骤：
(1)将含有蔗糖-6-乙酸酯的溶液依次进行氯化、碱金属氢氧化物中和、浓缩和水溶解，得到第一水溶液；所述第一水溶液为包括三氯蔗糖-6-乙酸酯、三氯蔗糖双酯和四氯蔗糖-6-乙酸酯的水溶液；
(2)将第一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，得到第一水相；所述第一水溶液为包括三氯蔗糖-6-乙酸酯、三氯蔗糖双酯和四氯蔗糖-6-乙酸酯的水溶液；
(3)将所述第一水相进行乙酸乙酯萃取，分别得到第一乙酯相和第二水相；
(4)将所述第一乙酯相进行水洗，分别得到第三水相和第二乙酯相；所述第三水相回用于步骤(2)中，所述回用时将所述第三水相与所述第一水溶液混合浓缩，然后再与碱金属氢氧化物混合；
(5)将所述第二乙酯相与乙酸乙酯混合，进行共沸脱水，得到第二乙酯相浓缩物；将所述第二乙酯相浓缩物与乙酸乙酯混合，得到第三乙酯相；
(6)将所述第三乙酯相进行结晶，分别得到三氯蔗糖粗品和第四乙酯相；
(7)将所述第四乙酯相进行水洗，分别得到第四水相和第五乙酯相；所述第四水相回用于步骤(2)中，所述回用时将所述第四水相与所述第一水溶液混合浓缩，然后再与碱金属氢氧化物混合。
优选地，步骤(2)中，所述碱解反应的pH值为12～13，温度为5～15℃，时间4～7h。
优选地，步骤(2)中，所述热过滤的温度为60～80℃。
优选地，步骤(3)中，所述乙酸乙酯萃取的温度为40～60℃；所述乙酸乙酯萃取的次数为5～7次；所述第一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一乙酯相；
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一水相的乙酸乙酯萃取。
优选地，步骤(3)中，所述第二水相中三氯蔗糖含量<0.5g/L。
优选地，步骤(4)中，所述水洗的次数为4～6次；所述第一乙酯相与水洗的单次用水的体积比为1：0.1～0.3；
将第1～2次水洗得到的水相合并作为第三水相；
将第3～6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一乙酯相的水洗。
优选地，步骤(4)中，所述第二水相中的三氯蔗糖的含量＜0.5g/L。
优选地，步骤(5)中，所述第二乙酯相浓缩液的水含量＜0.5wt％。
优选地，步骤(5)中，所述第三乙酯相的糖度为45～60wt％。
优选地，步骤(6)中，所述结晶的温度为40～60℃，时间24～36h。
优选地，步骤(7)中，所述第五乙酯相中三氯蔗糖含量<0.1g/L。
本发明提供了一种利用改进的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-水体系下直接对第一水溶液(含三氯蔗糖-6-乙酸酯、三氯蔗糖双酯和四氯蔗糖-6-乙酸酯)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，以蔗糖-6-乙酸酯为原料制备三氯蔗糖-6-乙酸酯的传统制备方法中，氯化后采用氨水进行中和，会产生大量的氯化铵，在碱解前需要乙 酸乙酯萃取以分离氯化铵(水相)和三氯蔗糖-6-乙酸酯(乙酸乙酯相)。而本发明采用碱金属氢氧化物中和代替传统的氨水中和，无需先进行乙酸乙酯萃取以分离氯化铵和三氯蔗糖-6-乙酸酯，可直接进行碱解，减少了乙酸乙酯溶剂的用量，同时避免了碱解过程中氯化铵分解产生氨气，而且，中和产生的盐均为氯化盐，在后续的乙酸乙酯萃取过程中被除去，减少了盐废水排放次数和排放量，缓解了后续环保处理压力。
附图说明
图1为实施例1利用改进的水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改进的水解体系制备三氯蔗糖粗品的方法，包括以下步骤：
(1)将含有蔗糖-6-乙酸酯的溶液依次进行氯化、碱金属氢氧化物中和、浓缩和水溶解，得到第一水溶液；所述第一水溶液为包括三氯蔗糖-6-乙酸酯、三氯蔗糖双酯和四氯蔗糖-6-乙酸酯的水溶液；
(2)将第一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，得到第一水相；所述第一水溶液为包括三氯蔗糖-6-乙酸酯、三氯蔗糖双酯和四氯蔗糖-6-乙酸酯的水溶液；
(3)将所述第一水相进行乙酸乙酯萃取，分别得到第一乙酯相和第二水相；
(4)将所述第一乙酯相进行水洗，分别得到第三水相和第二乙酯相；所述第三水相回用于步骤(2)中，所述回用时将所述第三水相与所述第一水溶液混合浓缩，然后再与碱金属氢氧化物混合；
(5)将所述第二乙酯相与乙酸乙酯混合，进行共沸脱水，得到第二乙酯相浓缩物；将所述第二乙酯相浓缩物与乙酸乙酯混合，得到第三乙酯相；
(6)将所述第三乙酯相进行结晶，分别得到三氯蔗糖粗品和第四乙酯相；
(7)将所述第四乙酯相进行水洗，分别得到第四水相和第五乙酯相； 所述第四水相回用于步骤(2)中，所述回用时将所述第四水相与所述第一水溶液混合浓缩，然后再与碱金属氢氧化物混合。
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。
本发明将含有蔗糖-6-乙酸酯的溶液依次进行氯化、碱金属氢氧化物中和、浓缩和水溶解，得到第一水溶液；所述第一水溶液为包括三氯蔗糖-6-乙酸酯、三氯蔗糖双酯和四氯蔗糖-6-乙酸酯的水溶液。
在本发明中，所述含有蔗糖-6-乙酸酯的溶液优选由蔗糖制备得到，具体的，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。本发明对于所述含有蔗糖-6-乙酸酯的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制备方法即可。
在本发明中，所述碱金属氢氧化物中和用碱金属氢氧化物优选包括氢氧化钠，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％。传统的以蔗糖-6-乙酸酯为原料制备三氯蔗糖-6-乙酸酯的过程中，氯化后采用氨水进行中和，会产生大量的氯化铵，在碱解前需要乙酸乙酯萃取以分离氯化铵(水相中)和三氯蔗糖-6-乙酸酯(乙酸乙酯相中)。而本发明采用碱金属氢氧化物中和代替传统的氨水中和，无需先进行乙酸乙酯萃取以分离氯化铵和三氯蔗糖-6-乙酸酯，直接进行碱解，减少了乙酸乙酯溶剂的用量，同时避免了碱解过程中氯化铵分解产生氨气，而且，中和产生的盐均为氯化盐，在后续的乙酸乙酯萃取过程中被除去，减少了盐废水排放次数和排放量，缓解了后续环保处理压力。此外，制备第一溶液时，采用氨水中和后需要浓缩回收DMF和三氯乙烷溶剂，为了避免溶剂残留(DMF在碱性条件下易分解)，在浓缩过程中需要加入新鲜无盐水作为共沸剂。而本发明采用碱金属氢氧化物进行中和，可使用三氯蔗糖粗品制备过程中产生的第三水相和第四水相作为共沸剂，避免了无盐水的使用，降低了生产成本。
本发明在制备第一水溶液过程中，采用碱金属氢氧化物代替传统的氨水进行中和，会导致第一水溶液中氯化盐总量增加，萃取难度增加，且第 二水相中氯化盐浓度过高易出现盐析，本发明通过控制乙酸乙酯的萃取次数，能够避免第二水相会因氯化盐浓度过高而产生盐析的现象；本发明通过平衡省略碱解前的乙酸乙酯萃取步骤移出的杂质，通过控制水洗次数将省略碱解前的乙酸乙酯萃取未移出的杂质平衡在循环套用的第四水相中。体系中水溶性杂质增加，影响了三氯蔗糖粗品的结晶，但只是影响了结晶时间，对三氯蔗糖的收率无太大影响。因此，本发明采用碱金属氢氧化物代替传统的氨水进行中和虽然导致第一水溶液中氯化盐总量增加，但是并不会影响三氯蔗糖的收率以及整体制备工艺的进行，而且能够显著降低乙酸乙酯的用量及高盐废水的排放量，并实现三氯蔗糖较高的收率。
在本发明中，所述第一水溶液中，三氯蔗糖-6-乙酸酯的含量优选为50～80g/L，更优选为55～75g/L；所述第一水溶液中三氯蔗糖-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；所述第一水溶液中优选还包括碱金属氯化盐和有机杂质，所述碱金属氯化盐的浓度优选为80～160g/L，更优选为80～120g/L，所述碱金属氯化盐优选包括NaCl和/或KCl，更优选为NaCl；所述有机杂质的浓度优选为25～70g/L，更优选为29～50g/L。
本发明对于所述氯化、浓缩和水溶解没有特殊限定，采用本领域技术人员熟知的的以蔗糖-6-乙酸酯为原料制备三氯蔗糖-6-乙酸酯的方法，得到上述组成的第一水溶液即可。
得到第一水溶液后，本发明将所述第一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，得到第一水相。
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，更优选为氢氧化钠，本发明以氢氧化钠为碱解反应的试剂，生产成本低；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12～13即可，所述pH值更优选为12.2～12.8，进一步优选为12.5；所述碱解反应的温度优选为5～15℃，更优选为8～12℃，进一步优选为10℃；所述碱解反应的时间优选为4～7h，更优选为4.5～6.5h，进一 步优选为5～6h。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60～80℃，更优选为65～75℃，进一步优选为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加热至60～80℃进行中和，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。
得到第一水相后，本发明将所述第一水相进行乙酸乙酯萃取，分别得到第一乙酯相和第二水相。
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℃；所述乙酸乙酯萃取的次数优选为5～7次；单次乙酸乙酯萃取的时间优选为10～30min，更优选为15～20min；所述第一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一乙酯相；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一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一水相的第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一水相的第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一水相的第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一水相的第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一水相的第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一水相的第1～5次乙酸乙酯萃取)，下一批次三氯蔗糖粗品的第一水相的第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，所述第二水相中三氯蔗糖含量优选<0.5g/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℃，单次乙酸乙酯萃取时间优选为10～30min，更优选为15～25min，所述乙酸乙酯萃取优选在搅拌条件下进行。
得到第一乙酯相后，本发明将所述第一乙酯相进行水洗，分别得到第三水相和第二乙酯相；所述第三水相回用于步骤(2)中，所述回用时将所述第三水相与所述第一水溶液混合浓缩，然后再与碱金属氢氧化物混合。
在本发明中，所述水洗的次数优选为4～6次；所述第一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1：0.15～0.25；本发明优选将第1～2次水洗得到的水相合并作为第三水相，优选将第3～6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一乙酯相的水洗，具体的，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一乙酯相的第1次水洗，第4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一乙酯相的第2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一乙酯相的第3次水洗，第6次水洗所得水相用于下一批次蔗糖粗品制备过程中第一乙酯相的第4次水洗(即第3～6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一乙酯相的第1～4次水洗)，下一批次三氯蔗糖粗品的第一乙酯相的第5～6次水洗优选利用纯水进行。
得到第二乙酯相后，本发明将所述第二乙酯相与乙酸乙酯混合，进行共沸脱水，得到第二乙酯相浓缩物；将所述第二乙酯相浓缩物与乙酸乙酯混合，得到第三乙酯相。
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，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，浓缩至所述第二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，以所述第三乙酯相的糖度(Bx)为45～60％为准，所述糖度更优选为50～55％。
得到第三乙酯相后，本发明将所述第三乙酯相进行结晶，分别得到三氯蔗糖粗品和第四乙酯相。
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24～36h，更优选为25～30h。三氯蔗糖在乙酸乙酯中的溶解度较低，本发明通过在第三水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，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四乙酯相。在本发明中，所述固液分离优选包括过滤或抽滤。
得到第四乙酯相后，本发明将所述第四乙酯相进行水洗，分别得到第四水相和第五乙酯相；所述第四水相回用于步骤(2)中，所述回用时将所述第四水相与所述第一水溶液混合浓缩，然后再与碱金属氢氧化物混合。
在本发明中，当所述第三水相和第四水相都回用于步骤(2)时，所述回用时，将所述第三水相、第四水相与所述第一水溶液混合浓缩，得到第一水浓缩液(第一水溶液、第三水相和第四水相的浓缩液)，然后将所述第一水浓缩液与碱金属氢氧化物混合；所述第一水溶液与第一水浓缩液的体积比优选为1：0.5～1，更优选为1：0.6～1。
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五乙酯相中三氯蔗糖含量<0.1g/L为准，具体如4～8次。在本发明中，所述第四乙酯相与水洗的单次用水的体积比优选为1：0.5～1，更优选为1：0.6～0.8。在本发明中，所述第五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，第四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四水相中，将第四水相进行循环利用，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。
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。
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)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、氢氧化钠水溶液中和、真空浓缩至干、加水溶解，得到第一水溶液。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 54.76g/L
三氯蔗糖双酯 2.93g/L
四氯蔗糖-6-乙酸酯 6.04g/L
NaCl 81.38g/L
其他有机杂质 29.11g/L
水 83.8％
(2)将1L第一水溶液置于三口瓶中，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℃、pH＝12.3的条件下碱解6h，滴加浓度为30wt％的稀盐酸中和至pH＝7，加热至70℃后热过滤，得到第 一水相(650mL，三氯蔗糖-6-乙酸酯含量为0.04g/L)和滤渣(固废处理)；
(3)向所述第一水相中加入1.3L乙酸乙酯，在45℃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一乙酯相(2.8L)，第3～6次萃取所得酯相依次用于下一批次三氯蔗糖粗品的制备过程中第一水相的第1～4次乙酸乙酯萃取。
(4)在所述第一乙酯相中加入550mL水进行水洗，水洗6次，第1～2次水洗所得水相为第三水相，所述第三水相用于步骤(2)中与所述第一水溶液混合后浓缩；第3～6次水洗得到的水相依次用于下一批次三氯蔗糖粗品的制备过程中所述第一乙酯相的第1～4次水洗，水洗结束后所得酯相为第二乙酯相。
(5)将所述第二乙酯相在70℃、-0.09MPa(表压)条件下浓缩，浓缩过程中加入乙酸乙酯(加入次数为3次，每次加入300mL)进行共沸脱水，在所得第二乙酯相浓缩物(水含量＜0.5wt％)中加入乙酸乙酯调节糖度至Bx为55％，得到第三乙酯相。
(6)将所述第三乙酯相在55℃条件下结晶30h，抽滤，分别得到三氯蔗糖粗品和第四乙酯相420mL(套用4次平衡后)。
(7)将所述第四乙酯相水洗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(固废处理)；合并水相作为第四水相，所述第四水相用于步骤(2)中与所述第一水溶液混合后浓缩。
(8)按照步骤(1)～(7)的操作(循环利用次数记为0次)，将所述第三水相和第四水相循环利用17次，得到的三氯蔗糖粗品的纯度及收率数据如表2所示；循环利用过程中，将步骤(2)中的“将1L第一水溶液置于三口瓶中”替换为“将第一水溶液置于茄形瓶中，加入所述第三水相和第四水相混合，在80℃、-0.08MPa条件下真空浓缩至600mL，然后转移至三口瓶中”；步骤(3)中，第一水相的第1～4次萃取依次利用上一批次三氯蔗糖粗品的制备过程中第一水相的第3～6次萃取所得酯相，第一水相的第5～6次乙酸乙酯萃取利用纯乙酸乙酯进行；步骤(4)中第一乙酯相的第1～4次水洗利用上一批次三氯蔗糖粗品的制备过程中第一乙酯相的第3～6次水洗得到的水相，第一乙酯相的第5～6次水洗利 用纯水进行。
表2 三氯蔗糖粗品纯度及收率
Figure PCTCN2022126043-appb-000001
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116.54％。
由表2可知，循环套用3次后，三氯蔗糖和杂质在乙酯相中处于一种平衡状态，即通过以下条件使得三氯蔗糖的收率稳定在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)第五乙酯相中的残糖需要达到制定标准；(5)结晶条件稳定。其中，收率以三氯蔗糖-6-乙酸酯全部转化为三氯蔗糖作为收率计算方式，收率超过了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。而且，第三水相和第四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。
综上所述，本发明提供的方法，未对第一水溶液进行乙酸乙酯萃取，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(第三水相和第四水相回用于步骤(2)中与所述第一水溶液混合浓缩，第一水相的的第3～7次乙酸乙酯萃取得到的乙酯相依次用于下一批次三氯蔗糖粗品制备过程中所述第一水相的第1～5次乙酸乙酯萃取，第一乙酯相的将第3～6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所述第一乙酯相的第1～4次水洗)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，具备很高的工业化应用价值。
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 (11)

  1. 一种利用改进的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)将含有蔗糖-6-乙酸酯的溶液依次进行氯化、碱金属氢氧化物中和、浓缩和水溶解，得到第一水溶液；所述第一水溶液为包括三氯蔗糖-6-乙酸酯、三氯蔗糖双酯和四氯蔗糖-6-乙酸酯的水溶液；
    (2)将第一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，得到第一水相；
    (3)将所述第一水相进行乙酸乙酯萃取，分别得到第一乙酯相和第二水相；
    (4)将所述第一乙酯相进行水洗，分别得到第三水相和第二乙酯相；所述第三水相回用于步骤(2)中，所述回用时将所述第三水相与所述第一水溶液混合浓缩，然后再与碱金属氢氧化物混合；
    (5)将所述第二乙酯相与乙酸乙酯混合，进行共沸脱水，得到第二乙酯相浓缩物；将所述第二乙酯相浓缩物与乙酸乙酯混合，得到第三乙酯相；
    (6)将所述第三乙酯相进行结晶，分别得到三氯蔗糖粗品和第四乙酯相；
    (7)将所述第四乙酯相进行水洗，分别得到第四水相和第五乙酯相；所述第四水相回用于步骤(2)中，所述回用时将所述第四水相与所述第一水溶液混合浓缩，然后再与碱金属氢氧化物混合。
  2. 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12～13，温度为5～15℃，时间4～7h。
  3. 根据权利要求1所述的方法，其特征在于，步骤(2)中，所述热过滤的温度为60～80℃。
  4. 根据权利要求1所述的方法，其特征在于，步骤(3)中，所述乙酸乙酯萃取的温度为40～60℃，所述乙酸乙酯萃取的次数为5～7次；所述第一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一乙酯相；
    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 制备过程中所述第一水相的乙酸乙酯萃取。
  5. 根据权利要求1或4所述的方法，其特征在于，步骤(3)中，所述第二水相中三氯蔗糖含量<0.5g/L。
  6. 根据权利要求1所述的方法，其特征在于，步骤(4)中，所述水洗的次数为4～6次；所述第一乙酯相与水洗的单次用水的体积比为1：0.1～0.3；
    将第1～2次水洗得到的水相合并作为第三水相；
    将第3～6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一乙酯相的水洗。
  7. 根据权利要求1或6所述的方法，其特征在于，步骤(4)中，所述第二水相中的三氯蔗糖的含量＜0.5g/L。
  8. 根据权利要求1所述的方法，其特征在于，步骤(5)中，所述第二乙酯相浓缩液的水含量＜0.5wt％。
  9. 根据权利要求1或8所述的方法，其特征在于，步骤(5)中，所述第三乙酯相的糖度为45～60wt％。
  10. 根据权利要求1所述的方法，其特征在于，步骤(6)中，所述结晶的温度为40～60℃，时间24～36h。
  11. 根据权利要求1所述的方法，其特征在于，步骤(7)中，所述第五乙酯相中三氯蔗糖含量<0.1g/L。
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Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN101941995A (zh) * 2009-07-10 2011-01-12 湖北益泰药业有限公司 一种提高三氯蔗糖-6-乙酸酯制备收率的方法
CN109956982A (zh) * 2019-03-29 2019-07-02 翁源广业清怡食品科技有限公司 一种三氯蔗糖的制备方法
CN113677689A (zh) * 2021-07-07 2021-11-19 安徽金禾实业股份有限公司 三氯蔗糖-6-酯的提纯方法
CN113717237A (zh) * 2021-08-17 2021-11-30 安徽金禾实业股份有限公司 一种从三氯蔗糖-6-乙酸酯中和液中制备三氯蔗糖的方法
CN113767109A (zh) * 2021-08-04 2021-12-07 安徽金禾实业股份有限公司 三氯蔗糖的制备方法
CN113939524A (zh) * 2021-07-07 2022-01-14 安徽金禾实业股份有限公司 三氯蔗糖-6-酯的提纯方法

Patent Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN101941995A (zh) * 2009-07-10 2011-01-12 湖北益泰药业有限公司 一种提高三氯蔗糖-6-乙酸酯制备收率的方法
CN109956982A (zh) * 2019-03-29 2019-07-02 翁源广业清怡食品科技有限公司 一种三氯蔗糖的制备方法
CN113677689A (zh) * 2021-07-07 2021-11-19 安徽金禾实业股份有限公司 三氯蔗糖-6-酯的提纯方法
CN113939524A (zh) * 2021-07-07 2022-01-14 安徽金禾实业股份有限公司 三氯蔗糖-6-酯的提纯方法
CN113767109A (zh) * 2021-08-04 2021-12-07 安徽金禾实业股份有限公司 三氯蔗糖的制备方法
CN113717237A (zh) * 2021-08-17 2021-11-30 安徽金禾实业股份有限公司 一种从三氯蔗糖-6-乙酸酯中和液中制备三氯蔗糖的方法

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