WO2024119464A1 - 一种三氯蔗糖的制备方法 - Google Patents

一种三氯蔗糖的制备方法 Download PDF

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WO2024119464A1
WO2024119464A1 PCT/CN2022/137842 CN2022137842W WO2024119464A1 WO 2024119464 A1 WO2024119464 A1 WO 2024119464A1 CN 2022137842 W CN2022137842 W CN 2022137842W WO 2024119464 A1 WO2024119464 A1 WO 2024119464A1
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sucralose
preparation
reaction
solution
aqueous phase
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PCT/CN2022/137842
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English (en)
French (fr)
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陈永乐
张正颂
张�浩
郭士雨
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安徽金禾实业股份有限公司
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Priority to CN202280005504.5A priority Critical patent/CN116368145A/zh
Priority to PCT/CN2022/137842 priority patent/WO2024119464A1/zh
Publication of WO2024119464A1 publication Critical patent/WO2024119464A1/zh

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  • the invention relates to the technical field of fine chemicals, and in particular to a method for preparing sucralose.
  • Sucralose is a sweetener developed by Tate & Lyle and the University of London in the United Kingdom and patented in 1976. It is currently the only functional sweetener made from sucrose, with a sweetness that is 600 times that of sucrose. Due to its pure taste, non-metabolism, high sweetness, no calories, good stability, and high safety, it has been widely used in beverages, food, daily chemicals, medicine and other fields, and is currently one of the best functional sweeteners.
  • the production process of sucralose mainly includes esterification, chlorination, alcoholysis, separation and purification, etc.
  • Its reaction mechanism is to use sucrose as raw material, N,N-dimethylformamide (DMF) as solvent and dehydrating agent, and organic tin ester as catalyst to protect the hydroxyl group at position 6 of sucrose to generate sucrose-6-butyl ester; then chlorinate in the presence of chlorination reagents such as thionyl chloride or phosgene to generate sucralose-6-acetate; finally, react in a methanol/sodium methoxide alcoholysis system or other alkaline hydrolysis system to generate sucralose.
  • This process is long, the amount of solvent used is large, there are many side reactions, and the yield of sucralose is not high, about 40%.
  • the object of the present invention is to provide a method for preparing sucralose.
  • the method provided by the present invention has a short process and a high yield of sucralose.
  • the technical solution adopted by the present invention is:
  • the present invention provides a method for preparing sucralose, comprising the following steps:
  • sucrose, N,N-dimethylformamide, trichloroethane and thionyl chloride to perform a chlorination reaction to obtain a chlorinated product solution; adjusting the pH value of the chlorinated product solution to alkaline, performing a decomposition reaction to obtain tetrachlorosucrose;
  • sucralose, water and an alkaline hydrolysis agent are mixed to perform an alkaline hydrolysis reaction to obtain sucralose.
  • the mixing of sucrose, N,N-dimethylformamide, trichloroethane and thionyl chloride comprises: mixing sucrose with N,N-dimethylformamide to obtain a sucrose constant volume solution; and sequentially dropping the thionyl chloride and the sucrose constant volume solution into the trichloroethane.
  • the sucrose constant volume solution also includes a vacuum dehydration treatment before use, the temperature of the vacuum dehydration treatment is 50-70°C, and the vacuum degree is -0.1MPa; the vacuum dehydration treatment ends when the water content in the condensed and collected N,N-dimethylformamide is less than 0.3wt%.
  • the dropwise addition of the thionyl chloride and the sucrose constant volume solution is performed at -5 to 5°C.
  • the dosage ratio of the sucrose to N,N-dimethylformamide is 1 g: (3-5) mL; the molar ratio of the sucrose to thionyl chloride is 1: (5-10); and the volume ratio of the thionyl chloride to trichloroethane is 1: (4-5).
  • the chlorination reaction includes sequentially performing a first stage insulation reaction, a first heating, a second stage insulation reaction, a second heating, a third stage insulation reaction, a third heating and a fourth stage insulation reaction;
  • the temperature of the first stage insulation reaction is 10-20°C, and the insulation time is 0.5-1h;
  • the temperature of the second stage insulation reaction is 35-45°C, and the insulation time is 0.5-1h;
  • the temperature of the third stage insulation reaction is 75-85°C, and the insulation time is 1-1.5h;
  • the temperature of the fourth stage insulation reaction is 100-110°C, and the insulation time is 1.5-2h.
  • the reagent used to adjust the pH value of the chlorinated product solution is an inorganic alkaline solution.
  • the inorganic alkali solution includes ammonia water, NaOH solution or KOH solution, and the concentration of the inorganic alkali solution is 15-30 wt%.
  • the temperature of the decomposition reaction is 0-10° C., and the insulation time is 0.5-1 h.
  • the decomposition reaction further comprises:
  • the pH value of the decomposition product liquid obtained by the decomposition reaction is adjusted to 6 to 8 to obtain a chlorinated neutralization liquid;
  • the chlorinated neutralized liquid is separated and purified to obtain tetrachlorosucrose.
  • the reagent used to adjust the pH value of the decomposition product solution is an inorganic acid.
  • the inorganic acid is hydrochloric acid; the concentration of the inorganic acid is 35 wt %.
  • the separation and purification comprises:
  • the second ester phase is concentrated to dryness to obtain sucralose.
  • the content of N,N-dimethylformamide in the first aqueous phase is less than 5 g/L, and the content of trichloroethane is less than 1 g/L.
  • the extraction is performed 4 to 6 times, and the volume ratio of butyl acetate to the first aqueous phase used in each extraction is (0.5 to 2):1.
  • the extraction further obtains a second aqueous phase, and the extraction is performed based on a standard that the content of sucralose in the second aqueous phase is less than 0.5 g/L.
  • the decolorizing material is activated carbon, and the volume ratio of the activated carbon to the first ester phase is (0.1-0.3) g:100 mL.
  • the water washing is performed 4 to 6 times, and the volume ratio of water used in each water washing to the first ester phase is (0.1 to 0.2):1.
  • the water washing further obtains a third aqueous phase; after obtaining the third aqueous phase, the method further comprises: extracting the third aqueous phase with butyl acetate to obtain a butyl acetate phase, and the butyl acetate phase is used to extract the next batch of first aqueous phases.
  • the third aqueous phase is extracted with butyl acetate 1 to 2 times, and the volume ratio of butyl acetate to the third aqueous phase used in each extraction is (0.5 to 2):1;
  • the third aqueous phase is extracted with butyl acetate to obtain a fourth aqueous phase, and the extraction is based on the content of sucralose in the fourth aqueous phase being less than 0.5 g/L.
  • the alkaline hydrolysis agent comprises tetramethylammonium hydroxide aqueous solution, tetraethylammonium hydroxide aqueous solution or tetrabutylammonium hydroxide aqueous solution; the concentration of the alkaline hydrolysis agent is 10wt% or 25wt%.
  • the conditions of the alkaline hydrolysis reaction include: pH value of 10.5-12.5, temperature of 0-10° C., and insulation time of 1-4 h.
  • the alkaline hydrolysis reaction further comprises:
  • the pH value of the alkaline hydrolysis product solution obtained by the alkaline hydrolysis reaction is adjusted to 6-8 by using hydrochloric acid to obtain a crude sucralose product aqueous solution;
  • the crude sucralose aqueous solution is concentrated to dryness, the residue is dissolved in methanol, the chloride salt is precipitated, and then solid-liquid separation is performed.
  • the obtained filtrate is concentrated to dryness, and the residue is dissolved in water to obtain an aqueous solution containing sucralose.
  • the volume of the methanol is 4 to 6 times the volume of the aqueous solution of crude sucralose.
  • the content of methanol in the aqueous solution containing sucralose is less than 0.3 g/L.
  • the present invention provides a method for preparing sucralose, comprising the following steps: mixing sucrose, N,N-dimethylformamide, trichloroethane and thionyl chloride, performing a chlorination reaction, and obtaining a chlorinated product liquid; adjusting the pH value of the chlorinated product liquid to alkaline, performing a decomposition reaction, and obtaining tetrachlorosucrose; mixing the tetrachlorosucrose, water and an alkaline hydrolysis agent, performing an alkaline hydrolysis reaction, and obtaining sucralose.
  • the present invention abandons the traditional method of protecting the hydroxyl group at position 6 of sucrose, and directly uses sucrose as a raw material for chlorination to prepare tetrachlorosucrose.
  • the chlorine atom group at position 6 of tetrachlorosucrose has higher activity than other groups, and can be dechlorinated at position 6 under the action of an alkaline hydrolysis agent to finally obtain sucralose.
  • the method provided by the present invention has a short process and a high yield of sucralose.
  • the method provided by the present invention has at least the following beneficial effects:
  • Butyl acetate is used as the extractant.
  • Sucralose has a high solubility in butyl acetate, which can realize the effective separation of sucralose from the system after the chlorination reaction, which is beneficial to reducing the difficulty of subsequent reactions and product purification;
  • the amount of N,N-dimethylformamide solvent used is greatly reduced, which is beneficial to reducing the cost and difficulty of solvent recovery, avoiding the problem of using a large amount of N,N-dimethylformamide solvent in the traditional process, resulting in the easy generation of N,N-dimethylacetamide (DMAC) and tetramethylurea by-products during the solvent recovery process, and alleviating the pressure of subsequent environmental protection treatment; 3.
  • DMAC N,N-dimethylacetamide
  • FIG. 1 is a flow chart of the preparation process of sucralose in the present invention.
  • the present invention provides a method for preparing sucralose, comprising the following steps:
  • sucrose, N,N-dimethylformamide, trichloroethane and thionyl chloride to perform a chlorination reaction to obtain a chlorinated product solution; adjusting the pH value of the chlorinated product solution to alkaline, performing a decomposition reaction to obtain tetrachlorosucrose;
  • sucralose, water and an alkaline hydrolysis agent are mixed to perform an alkaline hydrolysis reaction to obtain sucralose.
  • the raw materials used are commercially available products well known to those skilled in the art; unless otherwise specified, the water used in the present invention is pure water.
  • the present invention mixes sucrose, N,N-dimethylformamide, trichloroethane and thionyl chloride, performs chlorination reaction, and obtains chlorinated product liquid.
  • the dosage ratio of sucrose to N,N-dimethylformamide is preferably 1g:(3-5)mL, more preferably 1g:4mL;
  • the molar ratio of sucrose to thionyl chloride is preferably 1:(5-10), more preferably 1:(7-8);
  • the volume ratio of thionyl chloride to trichloroethane is preferably 1:(4-5), more preferably 1:4.5.
  • the mixing of sucrose, N,N-dimethylformamide, trichloroethane and thionyl chloride preferably includes: mixing sucrose with N,N-dimethylformamide to obtain a sucrose constant volume solution; sequentially adding the thionyl chloride and the sucrose constant volume solution to the trichloroethane.
  • the sucrose constant volume solution preferably also includes a vacuum dehydration treatment before use, and the temperature of the vacuum dehydration treatment is preferably 50-70°C, specifically 50°C, 60°C or 70°C, and a higher temperature easily causes sucrose to caramelize; the vacuum degree is preferably -0.1MPa, and the vacuum degree of the present invention is specifically the instrument pressure.
  • the present invention preferably mixes sucrose with N,N-dimethylformamide, heats to completely dissolve the sucrose, and then performs a vacuum dehydration treatment; the heating temperature is preferably 70-80°C, specifically 70°C, 75°C or 80°C.
  • the vacuum dehydration treatment is preferably terminated when the water content in the condensed and collected N,N-dimethylformamide is less than 0.3wt%.
  • the present invention preferably removes moisture from sucrose by vacuum dehydration treatment.
  • the sugar content in the sucrose constant volume solution after vacuum dehydration treatment is preferably 250-350 g/L.
  • the dropwise addition of the thionyl chloride and the sucrose constant volume solution is preferably performed at -5-5°C, more preferably -2-2°C.
  • the present invention has no special limitation on the dropwise addition rate of the thionyl chloride and the sucrose constant volume solution, as long as the system temperature is controlled within the above range.
  • the chlorination reaction preferably includes a first stage insulation reaction, a first heating, a second stage insulation reaction, a second heating, a third stage insulation reaction, a third heating and a fourth stage insulation reaction in sequence;
  • the temperature of the first stage insulation reaction is preferably 10-20°C, more preferably 15°C, and the insulation time is preferably 0.5-1h; after the first stage insulation reaction, the system temperature is raised to the temperature of the second stage insulation reaction by the first heating; the temperature of the second stage insulation reaction is preferably 35-45°C, more preferably 40°C, and the insulation time is preferably 0.5-1h; after the second stage insulation reaction, the system temperature is raised to the temperature of the third stage insulation reaction by the second heating; the temperature of the third stage insulation reaction is preferably 75-85°C, more preferably 80°C, and the insulation time is preferably 1-1.5h; after the third stage insulation reaction, the system temperature is raised to the temperature of the fourth stage insulation reaction by the third heating; the temperature of the fourth stage insulation reaction is preferably 100-
  • the present invention adjusts the pH value of the chlorinated product liquid to alkaline, performs a decomposition reaction, and obtains sucralose.
  • the reagent used to adjust the pH value of the chlorinated product liquid is preferably an inorganic alkali solution, and the inorganic alkali solution preferably includes ammonia water, NaOH solution or KOH solution, and the concentration of the inorganic alkali solution is preferably 15 to 30wt%.
  • the temperature of the decomposition reaction is preferably 0 to 10°C, more preferably 5°C; the insulation time is preferably 0.5 to 1h.
  • the decomposition reaction preferably further comprises:
  • the pH value of the decomposition product liquid obtained by the decomposition reaction is adjusted to 6 to 8 to obtain a chlorinated neutralization liquid;
  • the chlorinated neutralized liquid is separated and purified to obtain tetrachlorosucrose.
  • the present invention adjusts the pH value of the decomposition product liquid obtained by the decomposition reaction to 6-8 to obtain a chlorinated neutralized liquid.
  • the reagent used to adjust the pH value of the decomposition product liquid is preferably an inorganic acid, and the inorganic acid is preferably hydrochloric acid; the concentration of the inorganic acid is preferably 35wt%.
  • the present invention separates and purifies the chlorinated neutralized solution to obtain sucralose.
  • the separation and purification preferably includes:
  • the second ester phase is concentrated to dryness to obtain sucralose.
  • the present invention concentrates the chlorinated neutralized liquid to dryness, mixes the residue with water, and obtains a first aqueous phase.
  • the present invention preferably removes N,N-dimethylformamide and trichloroethane in the chlorinated neutralized liquid by concentrating the chlorinated neutralized liquid to dryness, and the N,N-dimethylformamide and trichloroethane can be recycled and reused.
  • the content of N,N-dimethylformamide in the first aqueous phase is preferably less than 5g/L, and the content of trichloroethane is preferably less than 1g/L.
  • the present invention uses butyl acetate to extract the first aqueous phase to obtain a first ester phase.
  • the extraction is preferably carried out at room temperature.
  • the number of extractions with butyl acetate is preferably 4 to 6 times;
  • the volume ratio of butyl acetate used in each extraction to the first aqueous phase is preferably (0.5 to 2): 1, more preferably 1: 1;
  • the present invention preferably combines the ester phases obtained from the first two butyl acetate extractions as the first ester phase; the ester phases obtained from the remaining batches of butyl acetate extractions are used for the butyl acetate extraction of the first aqueous phase in the next batch of sucralose preparation process.
  • the ester phase obtained from the third butyl acetate extraction is preferably used for the first butyl acetate extraction of the first aqueous phase in the next batch of sucralose preparation process
  • the ester phase obtained from the fourth butyl acetate extraction is preferably used for the next
  • the ester phase obtained by the second butyl acetate extraction and the fifth butyl acetate extraction of the first aqueous phase in the process of preparing a batch of sucralose is preferably used for the third butyl acetate extraction of the first aqueous phase in the process of preparing the next batch of sucralose
  • the ester phase obtained by the sixth butyl acetate extraction is preferably used for the fourth butyl acetate extraction of the first aqueous phase in the process of preparing the next batch of sucralose (i.e., the ester phases obtained by the third to sixth butyl acetate extractions are sequentially used for the first to fourth butyl acetate extraction
  • the first aqueous phase is preferably extracted with butyl acetate to obtain a second aqueous phase, and the extraction is preferably based on the content of sucralose in the second aqueous phase being less than 0.5 g/L; the second aqueous phase is high-salt wastewater, which can be treated in a conventional manner in the art.
  • the present invention decolorizes and washes the first ester phase in sequence to obtain a second ester phase.
  • the material used for decolorization is preferably activated carbon, and the volume ratio of the mass of the activated carbon to the first ester phase is preferably (0.1-0.3) g:100 mL, more preferably 0.2 g:100 mL.
  • the present invention preferably filters the obtained decolorized liquid and washes the obtained filtrate with water.
  • the number of water washings is preferably 4-6 times; the volume ratio of the water used for each water washing to the first ester phase is preferably (0.1-0.2):1, more preferably 0.15:1; the present invention preferably combines the aqueous phases obtained from the first two water washings as the third aqueous phase; the aqueous phases obtained from the remaining batches of water washings are preferably used for the washing of the first ester phase in the next batch of sucralose preparation process.
  • the aqueous phase obtained from the third water washing is used for the first water washing of the first ester phase in the next batch of sucralose preparation process
  • the aqueous phase obtained from the fourth water washing is used for the first water washing of the first ester phase in the next batch of sucralose preparation process.
  • the aqueous phase is used for the second water washing of the first ester phase in the next batch of sucralose preparation process
  • the aqueous phase obtained by the fifth water washing is used for the third water washing of the first ester phase in the next batch of sucrose preparation process
  • the aqueous phase obtained by the sixth water washing is used for the fourth water washing of the first ester phase in the next batch of sucrose preparation process (that is, the aqueous phases obtained by the third to sixth water washings are used in sequence for the first to fourth water washings of the first ester phase in the next batch of sucralose preparation process; preferably, the fifth to sixth water washings of the second ethyl ester phase in the next batch of sucralose crude preparation process are preferably carried out with pure water).
  • the water washing preferably also obtains a third aqueous phase; after obtaining the third aqueous phase, it is preferably further included: extracting the third aqueous phase with butyl acetate to obtain a butyl acetate phase, and the butyl acetate phase is used to extract the next batch of the first aqueous phase.
  • the number of times the third aqueous phase is extracted with butyl acetate is preferably 1 to 2 times, and the volume ratio of butyl acetate used in each extraction to the third aqueous phase is preferably (0.5 to 2):1.
  • the third aqueous phase is extracted with butyl acetate to obtain a fourth aqueous phase, and the extraction is based on the content of sucralose in the fourth aqueous phase being less than 0.5 g/L; the fourth aqueous phase is wastewater and can be treated according to conventional methods in the art.
  • the present invention concentrates the second ester phase to dryness to obtain sucralose.
  • the present invention preferably removes butyl acetate by concentrating the second ester phase to dryness, and the butyl acetate can be recycled and reused.
  • water is preferably added during the concentration process to assist desolventization.
  • the sucralose obtained after the second ester phase is concentrated to dryness is preferably directly subjected to a subsequent alkaline hydrolysis reaction.
  • the present invention mixes the sucralose, water and an alkaline hydrolysis agent to perform an alkaline hydrolysis reaction to obtain sucralose.
  • the alkaline hydrolysis agent preferably includes an aqueous solution of tetramethylammonium hydroxide, an aqueous solution of tetraethylammonium hydroxide or an aqueous solution of tetrabutylammonium hydroxide; the concentration of the alkaline hydrolysis agent is preferably 10wt% or 25wt% (both are commercially available products).
  • the sucralose obtained after the second ester phase is concentrated to dryness is mixed with water to obtain an aqueous solution of sucralose, and then an alkaline hydrolysis agent is added to the aqueous solution of sucralose; in the present invention, the content of butyl acetate in the aqueous solution of sucralose is preferably ⁇ 0.1g/L.
  • the conditions of the alkaline hydrolysis reaction preferably include: the pH value is preferably 10.5-12.5, more preferably 11.5; the temperature is preferably 0-10°C, more preferably 5°C; the insulation time is preferably 1-4h, more preferably 2.5h.
  • the present invention preferably performs an alkaline hydrolysis reaction under the above conditions, which can ensure the stability and high selectivity of the reaction and is conducive to the generation of sucralose.
  • the alkaline hydrolysis reaction preferably further comprises:
  • the pH value of the alkaline hydrolysis product solution obtained by the alkaline hydrolysis reaction is adjusted to 6-8 by using hydrochloric acid to obtain a crude sucralose product aqueous solution;
  • the crude sucralose aqueous solution is concentrated to dryness, the residue is dissolved in methanol, the chloride salt is precipitated, and then solid-liquid separation is performed.
  • the obtained filtrate is concentrated to dryness, and the residue is dissolved in water to obtain an aqueous solution containing sucralose.
  • the concentration of hydrochloric acid used to adjust the pH value of the alkaline hydrolysis product liquid is preferably 35wt%.
  • the volume of the methanol is preferably 4 to 6 times the volume of the crude sucralose aqueous solution.
  • sucralose is soluble in methanol, and chloride salt is insoluble in methanol, so the residue obtained by concentrating the crude sucralose aqueous solution to dryness can be dissolved in methanol to precipitate chloride salt, and then removed by solid-liquid separation.
  • the content of methanol in the aqueous solution containing sucralose is preferably ⁇ 0.3g/L.
  • the present invention preferably uses a method well known to those skilled in the art to separate sucralose, which will not be described in detail here.
  • the contents of sucrose, sucralose and tetrachlorosucrose were measured by high performance liquid chromatography (HPLC) based on the external standard method under the following conditions.
  • HPLC high performance liquid chromatography
  • the analytical conditions of the HPLC include: Shimadzu high performance liquid chromatograph, equipped with RID-10A differential refractometer, LC-10ADVP high pressure pump, CTO-10ASVP constant temperature box; the chromatographic column is Agilent XDB C18 column (250mm ⁇ 4.6mm, 5 ⁇ m); the mobile phase is methanol and 0.125wt% dipotassium hydrogen phosphate aqueous solution, and the volume ratio of methanol to dipotassium hydrogen phosphate aqueous solution is 4:6; the column temperature is 40°C; the mobile phase flow rate is 1.0mL/min; wherein methanol is chromatographically pure, dipotassium hydrogen phosphate is analytically pure, and water is ultrapure water.
  • Sucralose is prepared according to the process flow chart shown in FIG1 , and the specific steps are as follows:
  • Dehydration step 200 g of sucrose and 600 mL of N,N-dimethylformamide (DMF) were added to a three-necked flask in sequence, heated to 80°C for complete dissolution, then cooled to 50°C, and evacuated to a vacuum degree of -0.1 MPa (instrument pressure) for dehydration.
  • the dehydration was completed and 572 mL of sucrose constant volume solution was obtained.
  • the sucrose content in the sucrose constant volume solution was 349.28 g/L.
  • step (3) Separation step: 2801 mL of the chlorinated neutralized solution obtained in step (2) was concentrated to dryness, DMF and trichloroethane were recovered, pure water was added to assist desolventization during the concentration process, and finally the residue was diluted to 1000 mL with pure water to obtain a first aqueous phase, in which the DMF content was 4.23 g/L and the trichloroethane content was 0.72 g/L. Under room temperature (25° C.), the first aqueous phase was extracted with butyl acetate 6 times, and the volume of butyl acetate used for each extraction was 500 mL.
  • the ester phases obtained from the first two extractions were combined and recorded as the first ester phase, totaling 1183 mL.
  • the ester phases obtained from the last four extractions were used in the butyl acetate extraction step of the first aqueous phase in the next batch of sucralose preparation process; the raffinate aqueous phase was recorded as the second aqueous phase, totaling 703 mL, and was treated as wastewater.
  • the sucralose content in the second aqueous phase was 0.3 g/L. 3.54 g of activated carbon was added to the first ester phase for decolorization, and then the activated carbon was removed by filtration.
  • the first ester phase after decolorization was washed with pure water gradient for 6 times, and the volume of pure water used for each washing was 118 mL, to obtain 1070 mL of the second ester phase.
  • the aqueous phases obtained from the first 2 washings were combined and recorded as the third aqueous phase, a total of 281 mL, and the aqueous phases obtained from the last 4 washings were used in the washing step of the first ester phase in the preparation process of the next batch of sucralose.
  • the third aqueous phase was extracted with butyl acetate 2 times, and the volume of butyl acetate used for each extraction was 140 mL, to obtain 300 mL of butyl acetate phase, which was used for the next batch of extraction of the first aqueous phase, and the residual aqueous phase was recorded as the fourth aqueous phase, which was treated as wastewater, and the sucralose content in the fourth aqueous phase was 0.3 g/L.
  • the second ester phase is concentrated to dryness to recover butyl acetate. Pure water is added to assist desolventization during the concentration process.
  • the obtained residue is diluted to 1000 mL with pure water to obtain a tetrachlorosucrose aqueous solution, wherein the tetrachlorosucrose content of the tetrachlorosucrose aqueous solution is 174.55 g/L and the butyl acetate content is 0.07 g/L.
  • 35 wt % hydrochloric acid was added dropwise to the product system until the pH value of the system was 8, to obtain 1710 mL of a crude sucralose aqueous solution.
  • the crude sucralose aqueous solution is concentrated to dryness, methanol is added for azeotropy during the concentration process, and then the obtained residue is diluted to 6840 mL with methanol.
  • tetraethylammonium chloride is precipitated from the system and separated by suction filtration; the filtrate is concentrated to dryness, and methanol is recovered. Pure water is added to azeotropy with methanol during the concentration process to ensure low methanol residue.
  • the obtained residue is diluted to 1710 mL with pure water to obtain a sucralose aqueous solution, wherein the methanol content of the sucralose aqueous solution is 0.1 g/L, the sucralose content is 83.17 g/L, and the sucralose yield is 61.2%.
  • Dehydration step 200 g of sucrose and 800 mL of N,N-dimethylformamide (DMF) were added to a three-necked flask in sequence, and the mixture was heated to 75°C for complete dissolution. The mixture was then cooled to 60°C and evacuated to a vacuum degree of -0.1 MPa (instrument pressure) for dehydration. When the water content in the condensed and collected DMF was 0.25 wt%, the dehydration was completed, and 663 mL of sucrose constant volume solution was obtained, wherein the sucrose content in the sucrose constant volume solution was 301.32 g/L.
  • DMF N,N-dimethylformamide
  • step (3) Separation step: 2250 mL of the chlorinated neutralization solution obtained in step (2) was concentrated to dryness, DMF and trichloroethane were recovered, pure water was added to assist desolventization during the concentration process, and finally the residue was diluted to 1000 mL with pure water to obtain a first aqueous phase, in which the DMF content was 3.77 g/L and the trichloroethane content was 0.67 g/L. Under room temperature (25° C.), the first aqueous phase was extracted 5 times with butyl acetate, and the volume of butyl acetate used for each extraction was 1000 mL.
  • the ester phases obtained from the first two extractions were combined and recorded as the first ester phase, totaling 2186 mL.
  • the ester phases obtained from the last three extractions were used in the butyl acetate extraction step of the first aqueous phase in the next batch of sucralose preparation process; the raffinate aqueous phase was recorded as the second aqueous phase, totaling 691 mL, and was treated as wastewater.
  • the sucralose content in the second aqueous phase was 0.2 g/L. 4.36g of activated carbon was added to the first ester phase for decolorization, and then the activated carbon was removed by filtration.
  • the first ester phase after decolorization was washed with pure water gradient for 5 times, and the volume of pure water used for each washing was 438mL, to obtain 2065mL of the second ester phase.
  • the aqueous phases obtained from the first two washings were combined and recorded as the third aqueous phase, a total of 908mL, and the aqueous phases obtained from the last three washings were used in the washing step of the first ester phase in the preparation process of the next batch of sucralose.
  • the third aqueous phase was extracted once with 908mL of butyl acetate to obtain 932mL of butyl acetate phase, which was used for the next batch of extraction of the first aqueous phase.
  • the residual aqueous phase was recorded as the fourth aqueous phase and treated as wastewater.
  • the sucralose content in the fourth aqueous phase was 0.2g/L.
  • the second ester phase is concentrated to dryness to recover butyl acetate. Pure water is added to assist desolventization during the concentration process.
  • the obtained residue is diluted to 1000 mL with pure water to obtain a tetrachlorosucrose aqueous solution, wherein the tetrachlorosucrose content of the tetrachlorosucrose aqueous solution is 167.89 g/L and the butyl acetate content is 0.06 g/L.
  • 35 wt % hydrochloric acid was added dropwise to the product system until the pH value of the system was 6, to obtain 1472 mL of a crude sucralose aqueous solution.
  • the crude sucralose aqueous solution is concentrated to dryness, methanol is added for azeotropy during the concentration process, and then the obtained residue is diluted to 7360 mL with methanol.
  • tetrabutylammonium chloride is precipitated from the system and separated by suction filtration; the filtrate is concentrated to dryness, and methanol is recovered. Pure water is added for azeotropy with methanol during the concentration process to ensure low residual methanol.
  • the obtained residue is diluted to 1472 mL with pure water to obtain a sucralose aqueous solution, wherein the methanol content of the sucralose aqueous solution is 0.2 g/L, the sucralose content is 95.99 g/L, and the sucralose yield is 60.8%.
  • sucralose is prepared, and the specific steps are as follows:
  • Dehydration step 200 g of sucrose and 1000 mL of N,N-dimethylformamide (DMF) were added to a three-necked flask in sequence, and the mixture was heated to 70°C for complete dissolution. The temperature was then maintained at 70°C and the mixture was evacuated to a vacuum degree of -0.1 MPa (instrument pressure) for dehydration. When the water content in the condensed and collected DMF was 0.20 wt%, the dehydration was completed and 796 mL of a sucrose constant solution was obtained. The sucrose content in the sucrose constant solution was 251.01 g/L.
  • DMF N,N-dimethylformamide
  • step (3) Separation step: 2360 mL of the chlorinated neutralized solution obtained in step (2) was concentrated to dryness, DMF and trichloroethane were recovered, pure water was added to assist desolventization during the concentration process, and finally the residue was diluted to 1000 mL with pure water to obtain a first aqueous phase, in which the DMF content was 3.91 g/L and the trichloroethane content was 0.42 g/L. Under room temperature (25° C.), the first aqueous phase was extracted 4 times with butyl acetate, and the volume of butyl acetate used for each extraction was 2000 mL.
  • the ester phases obtained from the first two extractions were combined and recorded as the first ester phase, totaling 4193 mL.
  • the ester phases obtained from the second two extractions were used in the butyl acetate extraction step of the first aqueous phase in the next batch of sucralose preparation process; the raffinate aqueous phase was recorded as the second aqueous phase, totaling 685 mL, and was treated as wastewater.
  • the sucralose content in the second aqueous phase was 0.1 g/L. 4.19 g of activated carbon was added to the first ester phase for decolorization, and then the activated carbon was removed by filtration.
  • the first ester phase after decolorization was washed with pure water gradient water 4 times, and the volume of pure water used for each washing was 630 mL, and 4157 mL of the second ester phase was obtained.
  • the aqueous phases obtained from the first two washings were combined and recorded as the third aqueous phase, a total of 1321 mL, and the aqueous phases obtained from the last two washings were used in the washing step of the first ester phase in the preparation process of the next batch of sucralose.
  • the third aqueous phase was extracted once with 2642 mL of butyl acetate to obtain 2670 mL of butyl acetate phase, which was used for the next batch of extraction of the first aqueous phase.
  • the residual aqueous phase was recorded as the fourth aqueous phase and treated as wastewater.
  • the sucralose content in the fourth aqueous phase was 0.1 g/L.
  • the second ester phase is concentrated to dryness to recover butyl acetate. Pure water is added to assist desolventization during the concentration process.
  • the residue is diluted to 1000 mL with pure water to obtain a tetrachlorosucrose aqueous solution, wherein the tetrachlorosucrose content of the tetrachlorosucrose aqueous solution is 170.26 g/L and the butyl acetate content is 0.05 g/L.
  • the crude sucralose aqueous solution is concentrated to dryness, methanol is added for azeotropy during the concentration process, and then the obtained residue is diluted to 8742 mL with methanol.
  • tetramethylammonium chloride is precipitated from the system and separated by suction filtration; the filtrate is concentrated to dryness, methanol is recovered, pure water is added for azeotropy with methanol during the concentration process to ensure low methanol residue, and finally the obtained residue is diluted to 1457 mL with pure water to obtain a sucralose aqueous solution, wherein the methanol content of the sucralose aqueous solution is 0.1 g/L, the sucralose content is 100.50 g/L, and the sucralose yield is 63.0%.

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Abstract

一种三氯蔗糖的制备方法，属于精细化工技术领域。该制备方法包括以下步骤：将蔗糖、N,N-二甲基甲酰胺、三氯乙烷与氯化亚砜混合，进行氯化反应，得到氯化产物料液；将所述氯化产物料液的pH值调节至碱性，进行分解反应，得到四氯蔗糖；将所述四氯蔗糖、水与碱解剂混合，进行碱解反应，得到三氯蔗糖。本方法摒弃了传统的需要对蔗糖6号位进行羟基保护的方法，直接以蔗糖为原料进行氯化，制备得到四氯蔗糖，四氯蔗糖6号位的氯原子基团相对于其他基团具有更高的活性，可以在碱解剂作用下进行6号位的脱氯，最终得到三氯蔗糖。该方法流程短，且三氯蔗糖收率高。

Description

一种三氯蔗糖的制备方法 技术领域
本发明涉及精细化工技术领域，特别涉及一种三氯蔗糖的制备方法。
背景技术
三氯蔗糖(TGS)俗称蔗糖素，是由英国泰莱公司(Tate&Lyie)与伦敦大学共同研制并于1976年申请专利的一种甜味剂，且是目前唯一以蔗糖为原料的功能性甜味剂，甜度可达蔗糖的600倍。因其口感纯正，不参与代谢，且具有甜度高、无热量、稳定性好、安全性高等特点，已广泛应用于饮料、食品、日化、医药等多个领域，是目前最优秀的功能性甜味剂之一。
目前三氯蔗糖的生产工艺主要包括酯化、氯化、醇解以及分离提纯等步骤，其反应机理是以蔗糖为原料、N,N-二甲基甲酰胺(DMF)为溶剂和脱水剂、有机锡酯为催化剂对蔗糖6号位进行羟基保护，生成蔗糖-6-丁酯；然后在氯化亚砜或光气等氯化试剂的存在下氯化生成三氯蔗糖-6-乙酸酯；最后在甲醇/甲醇钠的醇解体系或其它碱解体系中反应，生成三氯蔗糖。该工艺流程长，溶剂使用量大，副反应多，且三氯蔗糖的收率不高，约为40％。
为提高三氯蔗糖的收率，降低成本，诸多研究院所及同行在各工段均开发出不少具有应用价值的工艺，如在醇解工段采用碱性离子交换树脂法(CN112409419A、CN102336787A)、碱金属氧化物法(CN113004345A、CN104004032A、CN112805291A)或碱金属氢氧化物法(CN1814609A、CN101012250A、CN102321122A)，来提高三氯蔗糖-6-乙酸酯生成三氯蔗糖的收率，降低体系中乙酸的含量，从而提高产品品质；又如从三氯蔗糖-6-乙酸酯提纯母液中经氧化或碱解回收三氯蔗糖-6-乙酸酯，从而提高三氯蔗糖的收率(CN113677689A、CN113939524A)。
然而，即便是在如上的技术提升下，三氯蔗糖的主体工艺依然没有改变，仍存在工艺流程长的问题，且三氯蔗糖的收率约为45％，仍较低。
发明内容
本发明的目的在于提供一种三氯蔗糖的制备方法，本发明提供的方法流程短，且三氯蔗糖收率高。
为了解决上述技术问题，本发明采用的技术方案是：
本发明提供了一种三氯蔗糖的制备方法，包括以下步骤：
将蔗糖、N,N-二甲基甲酰胺、三氯乙烷与氯化亚砜混合，进行氯化反应，得到氯化产物料液；将所述氯化产物料液的pH值调节至碱性，进行分解反应，得到四氯蔗糖；
将所述四氯蔗糖、水与碱解剂混合，进行碱解反应，得到三氯蔗糖。
优选地，所述蔗糖、N,N-二甲基甲酰胺、三氯乙烷与氯化亚砜混合包括：将蔗糖与N,N-二甲基甲酰胺混合，得到蔗糖定容液；向所述三氯乙烷中依次滴加所述氯化亚砜与所述蔗糖定容液。
优选地，所述蔗糖定容液使用前还包括真空脱水处理，所述真空脱水处理的温度为50～70℃，真空度为-0.1MPa；所述真空脱水处理在冷凝收集的N,N-二甲基甲酰胺中水含量＜0.3wt％时结束。
优选地，滴加所述氯化亚砜与所述蔗糖定容液在-5～5℃条件下进行。
优选地，所述蔗糖与N,N-二甲基甲酰胺的用量比为1g：(3～5)mL；所述蔗糖与氯化亚砜的摩尔比为1：(5～10)；所述氯化亚砜与三氯乙烷的体积比为1：(4～5)。
优选地，所述氯化反应包括依次进行第一阶段保温反应、第一升温、第二阶段保温反应、第二升温、第三阶段保温反应、第三升温和第四阶段保温反应；所述第一阶段保温反应的温度为10～20℃，保温时间为0.5～1h；所述第二阶段保温反应的温度为35～45℃，保温时间为0.5～1h；所述第三阶段保温反应的温度为75～85℃，保温时间为1～1.5h；所述第四阶段保温反应的温度为100～110℃，保温时间为1.5～2h。
优选地，调节所述氯化产物料液的pH值至碱性在0～10℃条件下进行；所述碱性为pH＝9～11。
优选地，调节所述氯化产物料液pH值所用试剂为无机碱溶液。
优选地，所述无机碱溶液包括氨水、NaOH溶液或KOH溶液，所述无机碱溶液的浓度为15～30wt％。
优选地，所述分解反应的温度为0～10℃，保温时间为0.5～1h。
优选地，所述分解反应后还包括：
将分解反应所得分解产物料液的pH值调节至6～8，得到氯化中和液；
将所述氯化中和液进行分离纯化，得到四氯蔗糖。
优选地，调节所述分解产物料液pH值所用试剂为无机酸。
优选地，所述无机酸为盐酸；所述无机酸的浓度为35wt％。
优选地，所述分离纯化包括：
将所述氯化中和液浓缩至干，将剩余物与水混合，得到第一水相；
采用乙酸丁酯对所述第一水相进行萃取，得到第一酯相；
将所述第一酯相依次进行脱色和水洗，得到第二酯相；
将所述第二酯相浓缩至干，得到四氯蔗糖。
优选地，所述第一水相中N,N-二甲基甲酰胺的含量＜5g/L，三氯乙烷的含量＜1g/L。
优选地，所述萃取的次数为4～6次，每次萃取所用乙酸丁酯与第一水相体积比为(0.5～2)：1。
优选地，所述萃取还得到第二水相，所述萃取以使所述第二水相中四氯蔗糖的含量＜0.5g/L为基准。
优选地，所述脱色所用材料为活性炭，所述活性炭的质量与第一酯相的体积比为(0.1～0.3)g：100mL。
优选地，所述水洗的次数为4～6次，每次水洗所用水与第一酯相的体积比为(0.1～0.2)：1。
优选地，所述水洗还得到第三水相；得到所述第三水相后还包括：采用乙酸丁酯对所述第三水相进行萃取，得到乙酸丁酯相，所述乙酸丁酯相回用于对下一批次第一水相进行萃取。
优选地，采用乙酸丁酯对所述第三水相进行萃取的次数为1～2次，每次萃取所用乙酸丁酯与第三水相的体积比为(0.5～2)：1；
采用乙酸丁酯对所述第三水相进行萃取还得到第四水相，所述萃取以使所述第四水相中四氯蔗糖的含量＜0.5g/L为基准。
优选地，所述碱解剂包括四甲基氢氧化铵水溶液、四乙基氢氧化铵水溶液或四丁基氢氧化铵水溶液；所述碱解剂的浓度为10wt％或25wt％。
优选地，所述碱解反应的条件包括：pH值为10.5～12.5，温度为0～10℃，保温时间为1～4h。
优选地，所述碱解反应后还包括：
采用盐酸将碱解反应所得碱解产物料液的pH值调节至6～8，得到三氯蔗糖粗产物水溶液；
将所述三氯蔗糖粗产物水溶液浓缩至干，将剩余物溶解于甲醇中，析出氯盐后经固液分离，将所得滤液浓缩至干，将剩余物溶解于水中，得到含三氯蔗糖的水溶液。
优选地，所述甲醇的体积为三氯蔗糖粗产物水溶液体积的4～6倍。
优选地，所述含三氯蔗糖的水溶液中甲醇的含量＜0.3g/L。
本发明提供了一种三氯蔗糖的制备方法，包括以下步骤：将蔗糖、N,N-二甲基甲酰胺、三氯乙烷与氯化亚砜混合，进行氯化反应，得到氯化产物料液；将所述氯化产物料液的pH值调节至碱性，进行分解反应，得到四氯蔗糖；将所述四氯蔗糖、水与碱解剂混合，进行碱解反应，得到三氯蔗糖。本发明摒弃了传统的需要对蔗糖6号位进行羟基保护的方法，直接以蔗糖为原料进行氯化，制备得到四氯蔗糖，四氯蔗糖6号位的氯原子基团相对于其他基团具有更高的活性，可以在碱解剂作用下进行6号位的脱氯，最终得到三氯蔗糖。本发明提供的方法流程短，且三氯蔗糖收率高。
进一步地，本发明提供的方法至少还具有以下有益效果：
1、采用乙酸丁酯作为萃取剂，四氯蔗糖在乙酸丁酯中具有较高的溶解性，可实现氯化反应后四氯蔗糖与体系的有效分离，有利于降低后续反应及产品提纯的难度；2、大大降低了N,N-二甲基甲酰胺溶剂的使用量，有利于降低溶剂回收成本及难度，避免了传统工艺中使用大量N,N-二甲基甲酰胺溶剂，导致溶剂回收过程中易产生N,N-二甲基乙酰胺(DMAC)和四甲基脲副产物的问题，缓解了后续环保处理的压力；3、不会产生乙酸副产物，解决了传统工艺中乙酸对设备存在腐蚀及对产品品质有不良影响的问题；4、舍去了有机锡催化剂的使用，从而杜绝了金属锡对产品和环境的威胁；5、缩短反应流程有利于减少副反应的发生，成本低，设备投入少，稳定性高，具备较好的工业应用价值。
附图说明
图1为本发明中三氯蔗糖的制备工艺流程图。
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。
本发明提供了一种三氯蔗糖的制备方法，包括以下步骤：
将蔗糖、N,N-二甲基甲酰胺、三氯乙烷与氯化亚砜混合，进行氯化反应，得到氯化产物料液；将所述氯化产物料液的pH值调节至碱性，进行分解反应，得到四氯蔗糖；
将所述四氯蔗糖、水与碱解剂混合，进行碱解反应，得到三氯蔗糖。
在本发明中，若无特殊说明，所用原料均为本领域技术人员熟知的市售商品；若无特殊说明，本发明所用水为纯水。
本发明将蔗糖、N,N-二甲基甲酰胺、三氯乙烷与氯化亚砜混合，进行氯化反应，得到氯化产物料液。在本发明中，所述蔗糖与N,N-二甲基甲酰胺的用量比优选为1g：(3～5)mL，更优选为1g：4mL；所述蔗糖与氯化亚砜的摩尔比优选为1：(5～10)，更优选为1：(7～8)；所述氯化亚砜与三氯乙烷的体积比优选为1：(4～5)，更优选为1：4.5。
在本发明中，所述蔗糖、N,N-二甲基甲酰胺、三氯乙烷与氯化亚砜混合优选包括：将蔗糖与N,N-二甲基甲酰胺混合，得到蔗糖定容液；向所述三氯乙烷中依次滴加所述氯化亚砜与所述蔗糖定容液。在本发明中，所述蔗糖定容液使用前优选还包括真空脱水处理，所述真空脱水处理的温度优选为50～70℃，具体可以为50℃、60℃或70℃，温度较高容易导致蔗糖焦化；真空度优选为-0.1MPa，本发明所述真空度具体为仪表压力。本发明优选将蔗糖与N,N-二甲基甲酰胺混合，加热使蔗糖完全溶解，然后进行真空脱水处理；所述加热的温度优选为70～80℃，具可以为70℃、75℃或80℃。在本发明中，所述真空脱水处理优选在冷凝收集的N,N-二甲基甲酰胺中水含量＜0.3wt％时结束。本发明优选通过真空脱水处理去除蔗糖中的水分。在本发明中，所述真空脱水处理后的蔗糖定容液中糖含量优选为250～350g/L。在本发明中，滴加所述氯化亚砜与所述蔗糖定容 液优选在-5～5℃条件下进行，更优选为-2～2℃。本发明对所述氯化亚砜与所述蔗糖定容液的滴加速率没有特殊限定，保证体系温度控制在上述范围即可。
在本发明中，所述氯化反应优选包括依次进行第一阶段保温反应、第一升温、第二阶段保温反应、第二升温、第三阶段保温反应、第三升温和第四阶段保温反应；所述第一阶段保温反应的温度优选为10～20℃，更优选为15℃，保温时间优选为0.5～1h；所述第一阶段保温反应后经第一升温将体系温度升至第二阶段保温反应的温度；所述第二阶段保温反应的温度优选为35～45℃，更优选为40℃，保温时间优选为0.5～1h；所述第二阶段保温反应后经第二升温将体系温度升至第三阶段保温反应的温度；所述第三阶段保温反应的温度优选为75～85℃，更优选为80℃，保温时间优选为1～1.5h；所述第三阶段保温反应后经第三升温将体系温度升至第四阶段保温反应的温度；所述第四阶段保温反应的温度优选为100～110℃，更优选为105℃，保温时间优选为1.5～2h。本发明将氯化反应分为上述阶段，能够有效反应，将蔗糖转化为四氯蔗糖，有利于后续三氯蔗糖的制备与分离。
得到氯化产物料液后，本发明将所述氯化产物料液的pH值调节至碱性，进行分解反应，得到四氯蔗糖。在本发明中，调节所述氯化产物料液的pH值至碱性优选在0～10℃条件下进行，更优选为5℃；所述碱性优选为pH＝9～11，更优选为10。在本发明中，调节所述氯化产物料液pH值所用试剂优选为无机碱溶液，所述无机碱溶液优选包括氨水、NaOH溶液或KOH溶液，所述无机碱溶液的浓度优选为15～30wt％。在本发明中，所述分解反应的温度优选为0～10℃，更优选为5℃；保温时间优选为0.5～1h。
在本发明中，所述分解反应后优选还包括：
将分解反应所得分解产物料液的pH值调节至6～8，得到氯化中和液；
将所述氯化中和液进行分离纯化，得到四氯蔗糖。
本发明将分解反应所得分解产物料液的pH值调节至6～8，得到氯化中和液。在本发明中，调节所述分解产物料液pH值所用试剂优选为无机酸，所述无机酸优选为盐酸；所述无机酸的浓度优选为35wt％。
得到氯化中和液后，本发明将所述氯化中和液进行分离纯化，得到四氯蔗糖。在本发明中，所述分离纯化优选包括：
将所述氯化中和液浓缩至干，将剩余物与水混合，得到第一水相；
采用乙酸丁酯对所述第一水相进行萃取，得到第一酯相；
将所述第一酯相依次进行脱色和水洗，得到第二酯相；
将所述第二酯相浓缩至干，得到四氯蔗糖。
本发明将所述氯化中和液浓缩至干，将剩余物与水混合，得到第一水相。本发明优选通过将所述氯化中和液浓缩至干，去除所述氯化中和液中的N,N-二甲基甲酰胺和三氯乙烷，所述N,N-二甲基甲酰胺和三氯乙烷可回收再利用。在本发明中，为了便于实现N,N-二甲基甲酰胺和三氯乙烷的充分去除，优选在所述浓缩过程中加水助脱溶。在本发明中，所述第一水相中N,N-二甲基甲酰胺的含量优选＜5g/L，三氯乙烷的含量优选＜1g/L。
得到第一水相后，本发明采用乙酸丁酯对所述第一水相进行萃取，得到第一酯相。在本发明中，所述萃取优选在室温条件下进行。在本发明中，采用所述乙酸丁酯萃取的次数优选为4～6次；每次萃取所用乙酸丁酯与第一水相的体积比优选为(0.5～2)：1，更优选为1:1；本发明优选将前2次乙酸丁酯萃取得到的酯相合并作为第一酯相；将剩余批次乙酸丁酯萃取所得酯相用于下一批次三氯蔗糖制备过程中第一水相的乙酸丁酯萃取，具体的，以萃取6次为例，第3次乙酸丁酯萃取获得的酯相优选用于下一批次三氯蔗糖制备过程中第一水相的第1次乙酸丁酯萃取，第4次乙酸丁酯萃取获得的酯相优选用于下一批次三氯蔗糖制备过程中第一水相的第2次乙酸丁酯萃取，第5次乙酸丁酯萃取获得的酯相优选用于下一批次三氯蔗糖制备过程中第一水相的第3次乙酸丁酯萃取，第6次乙酸丁酯萃取获得的酯相优选用于下一批次三氯蔗糖制备过程中第一水相的第4次乙酸丁酯萃取(即第3～6次乙酸丁酯萃取获得的酯相依次用于下一批次三氯蔗糖制备过程中第一水相的第1～4次乙酸丁酯萃取；优选地，下一批次三氯蔗糖制备过程中第一水相的第5～6次乙酸丁酯萃取优选利用纯乙酸丁酯进行)。在本发明中，采用乙酸丁酯对所述第一水相进行萃取优选还得到第二水相，所述萃取优选以使所述第二水相中四氯蔗糖的含量＜ 0.5g/L为基准；所述第二水相为高盐废水，按照本领域常规方式对其进行处理即可。
得到第一酯相后，本发明将所述第一酯相依次进行脱色和水洗，得到第二酯相。在本发明中，所述脱色所用材料优选为活性炭，所述活性炭的质量与第一酯相的体积比优选为(0.1～0.3)g：100mL，更优选为0.2g：100mL。所述脱色后，本发明优选将所得脱色料液进行过滤，将所得滤液进行水洗。在本发明中，所述水洗的次数优选为4～6次；每次水洗所用水与第一酯相的体积比优选为(0.1～0.2)：1，更优选为0.15：1；本发明优选将前2次水洗得到的水相合并作为第三水相；将剩余批次水洗得到的水相优选用于下一批次三氯蔗糖制备过程中所述第一酯相的水洗，具体的，以水洗6次为例，第3次水洗获得的水相用于下一批次三氯蔗糖制备过程中第一酯相的第1次水洗，第4次水洗获得的水相用于下一批次三氯蔗糖制备过程中第一酯相的第2次水洗，第5次水洗获得的水相用于下一批次蔗糖制备过程中第一酯相的第3次水洗，第6次水洗获得的水相用于下一批次蔗糖制备过程中第一酯相的第4次水洗(即第3～6次水洗获得的水相依次用于下一批次三氯蔗糖制备过程中第一酯相的第1～4次水洗；优选地，下一批次三氯蔗糖粗品制备过程中第二乙酯相的的第5～6次水洗优选利用纯水进行)。在本发明中，所述水洗优选还得到第三水相；得到所述第三水相后优选还包括：采用乙酸丁酯对所述第三水相进行萃取，得到乙酸丁酯相，所述乙酸丁酯相回用于对下一批次第一水相进行萃取。在本发明中，采用乙酸丁酯对所述第三水相进行萃取的次数优选为1～2次，每次萃取所用乙酸丁酯与第三水相的体积比优选为(0.5～2)：1。在本发明中，采用乙酸丁酯对所述第三水相进行萃取优选还得到第四水相，所述萃取以使所述第四水相中四氯蔗糖的含量＜0.5g/L为基准；所述第四水相为废水，按照本领域常规方式对其进行处理即可。
得到第二酯相后，本发明将所述第二酯相浓缩至干，得到四氯蔗糖。在本发明中，本发明优选通过将所述第二酯相浓缩至干，去除乙酸丁酯，所述乙酸丁酯可回收再利用。在本发明中，为了便于实现乙酸丁酯的充分去除，优选在所述浓缩过程中加水助脱溶。本发明优选将第二酯相浓缩至干后所得四氯蔗糖直接进行后续碱解反应。
得到四氯蔗糖后，本发明将所述四氯蔗糖、水与碱解剂混合，进行碱解反应，得到三氯蔗糖。在本发明中，所述碱解剂优选包括四甲基氢氧化铵水溶液、四乙基氢氧化铵水溶液或四丁基氢氧化铵水溶液；所述碱解剂的浓度优选为10wt％或25wt％(均为市售商品)。本发明优选将第二酯相浓缩至干后所得四氯蔗糖与水混合，得到四氯蔗糖水溶液，然后向所述四氯蔗糖水溶液中加入碱解剂；在本发明中，所述四氯蔗糖水溶液中乙酸丁酯含量优选＜0.1g/L。在本发明中，所述碱解反应的条件优选包括：pH值优选为10.5～12.5，更优选为11.5；温度优选为0～10℃，更优选为5℃；保温时间优选为1～4h，更优选为2.5h。本发明优选在上述条件下进行碱解反应，能够确保反应的稳定性和高选择性，有利于生成三氯蔗糖。
在本发明中，所述碱解反应后优选还包括：
采用盐酸将碱解反应所得碱解产物料液的pH值调节至6～8，得到三氯蔗糖粗产物水溶液；
将所述三氯蔗糖粗产物水溶液浓缩至干，将剩余物溶解于甲醇中，析出氯盐后经固液分离，将所得滤液浓缩至干，将剩余物溶解于水中，得到含三氯蔗糖的水溶液。
在本发明中，调节所述碱解产物料液pH值所用盐酸的浓度优选为35wt％。在本发明中，所述甲醇的体积优选为三氯蔗糖粗产物水溶液体积的4～6倍。在本发明中，三氯蔗糖溶于甲醇中，氯盐不溶于甲醇，故可以通过将所述三氯蔗糖粗产物水溶液浓缩至干所得剩余物溶解于甲醇中，使氯盐析出，再经固液分离将其去除。在本发明中，所述含三氯蔗糖的水溶液中甲醇的含量优选＜0.3g/L。
得到含三氯蔗糖的水溶液后，本发明优选采用本领域技术人员熟知的方法分离得到三氯蔗糖，在此不再赘述。
下面结合实施例对本发明提供的三氯蔗糖的制备方法进行详细地描述，但不能将它们理解为对本发明保护范围的限定。
以下各实施例中蔗糖、三氯蔗糖和四氯蔗糖的含量均采用高效液相色谱(High Performance Liquid Chromatography，HPLC)在下述条件下基于外标法测得，高效液相色谱的分析测定条件包括：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；色谱柱为Agilent XDB C18柱(250mm×4.6mm，5μm)；流动相为甲醇与浓度为0.125wt％的磷酸氢二钾水溶液，所述甲醇与磷酸氢二钾水溶液的体积比为4:6；柱温为40℃；流动相流量为1.0mL/min；其中，甲醇为色谱纯，磷酸氢二钾为分析纯，水为超纯水。
实施例1
按照图1所示的工艺流程图制备三氯蔗糖，具体步骤如下：
(1)脱水步骤：在三口烧瓶中依次加入200g蔗糖和600mL N,N-二甲基甲酰胺(DMF)，加热至80℃完全溶解，然后降温至50℃，抽真空至真空度为-0.1MPa(仪表压力)，进行脱水，当冷凝收集的DMF中水含量为0.29wt％时，脱水完毕，得到蔗糖定容液572mL，所述蔗糖定容液中蔗糖含量为349.28g/L。
(2)氯化反应步骤：在三口烧瓶中加入1700mL三氯乙烷，向所述三氯乙烷中滴加424mL氯化亚砜，滴加过程中控制体系温度为-5℃；氯化亚砜滴加完毕后，再滴加步骤(1)所得蔗糖定容液572mL；蔗糖定容液滴加完毕后，依次升温至10℃保温反应1h、升温至35℃保温反应1h、升温至75℃保温反应1.5h、升温至100℃保温反应2h；反应结束后，将所得产物体系降温至0℃，在搅拌条件下滴加浓度为20wt％的氨水，将体系pH值调节至9后反应1h，之后用浓度为35wt％的盐酸将所得产物体系pH值调节至6，得到氯化中和液2801mL。
(3)分离步骤：将步骤(2)所得氯化中和液2801mL浓缩至干，回收DMF和三氯乙烷，浓缩过程中加纯水助脱溶，最后将所得剩余物用纯水定容至1000mL，得到第一水相，所述第一水相中DMF含量为4.23g/L，三氯乙烷含量为0.72g/L。在室温(25℃)条件下，采用乙酸丁酯萃取所述第一水相6次，每次萃取所用乙酸丁酯的体积为500mL，萃取过程中将前2次萃取所得酯相合并，记为第一酯相，共1183mL，后4次萃取所得酯相用于下一批次三氯蔗糖制备过程中第一水相的乙酸丁酯萃取步骤中；萃余水相记为第二水相，共703mL，作为废水进行处理，所述第二水相中四氯蔗糖含量为0.3g/L。向所述第一酯相中加入3.54g活性炭进行脱色，之后过滤去除活性炭，采用纯水梯度水洗脱色后的第一酯相6次，每次水洗所用纯水的体积为118mL，得到1070mL第二酯相，纯水洗涤过 程中将前2次水洗所得水相合并，记为第三水相，共281mL，后4次水洗所得水相用于下一批次三氯蔗糖制备过程中所述第一酯相的水洗步骤中。采用乙酸丁酯萃取所述第三水相2次，每次萃取所用乙酸丁酯的体积为140mL，得到300mL乙酸丁酯相，用于下一批次萃取第一水相，萃余水相记为第四水相，作为废水进行处理，所述第四水相中四氯蔗糖含量为0.3g/L。将所述第二酯相浓缩至干，回收乙酸丁酯，浓缩过程中加纯水助脱溶，最后将所得剩余物用纯水定容至1000mL，得到四氯蔗糖水溶液，所述四氯蔗糖水溶液中四氯蔗糖含量为174.55g/L，乙酸丁酯含量为0.07g/L。
(4)碱解步骤：将步骤(3)所得四氯蔗糖水溶液1000mL降温至0℃，滴加浓度为10wt％的四乙基氢氧化铵水溶液，滴加过程中控制体系温度为0℃，至体系pH值为11.5时停止滴加，之后保温反应2.5h；反应结束后所得产物体系中四氯蔗糖含量为0.3g/L，向所述产物体系中滴加浓度为35wt％的盐酸至体系pH值为8，得到1710mL三氯蔗糖粗产物水溶液。将所述三氯蔗糖粗产物水溶液浓缩至干，浓缩过程中加甲醇共沸，然后将所得剩余物用甲醇定容至6840mL，此时四乙基氯化铵从体系中析出，抽滤分离；将滤液浓缩至干，回收甲醇，浓缩过程中加纯水与甲醇共沸，确保甲醇低残留，最后将所得剩余物用纯水定容至1710mL，得到三氯蔗糖水溶液，所述三氯蔗糖水溶液中甲醇含量0.1g/L，三氯蔗糖含量为83.17g/L，三氯蔗糖收率为61.2％。
实施例2
(1)脱水步骤：在三口烧瓶中依次加入200g蔗糖和800mL N,N-二甲基甲酰胺(DMF)，加热至75℃完全溶解，然后降温至60℃，抽真空至真空度为-0.1MPa(仪表压力)，进行脱水，当冷凝收集的DMF中水含量为0.25wt％时，脱水完毕，得到蔗糖定容液663mL，所述蔗糖定容液中蔗糖含量为301.32g/L。
(2)氯化反应步骤：在三口烧瓶中加入1350mL三氯乙烷，向所述三氯乙烷中滴加300mL氯化亚砜，滴加过程中控制体系温度为0℃；氯化亚砜滴加完毕后，再滴加步骤(1)所得蔗糖定容液663mL；蔗糖定容液滴加完毕后，依次升温至15℃保温反应45min、升温至40℃保温反应 45min、升温至80℃保温反应1h45min、升温至105℃保温反应1h 15min；反应结束后，将所得产物体系降温至5℃，在搅拌条件下滴加浓度为20wt％的氨水，将体系pH值调节至10后反应45min，之后用浓度为35wt％的盐酸将所得产物体系pH值调节至7，得到氯化中和液2250mL。
(3)分离步骤：将步骤(2)所得氯化中和液2250mL浓缩至干，回收DMF和三氯乙烷，浓缩过程中加纯水助脱溶，最后将所得剩余物用纯水定容至1000mL，得到第一水相，所述第一水相中DMF含量为3.77g/L，三氯乙烷含量为0.67g/L。在室温(25℃)条件下，采用乙酸丁酯萃取所述第一水相5次，每次萃取所用乙酸丁酯的体积为1000mL，萃取过程中将前2次萃取所得酯相合并，记为第一酯相，共2186mL，后3次萃取所得酯相用于下一批次三氯蔗糖制备过程中第一水相的乙酸丁酯萃取步骤中；萃余水相记为第二水相，共691mL，作为废水进行处理，所述第二水相中四氯蔗糖含量为0.2g/L。向所述第一酯相中加入4.36g活性炭进行脱色，之后过滤去除活性炭，采用纯水梯度水洗脱色后的第一酯相5次，每次水洗所用纯水的体积为438mL，得到2065mL第二酯相，纯水洗涤过程中将前2次水洗所得水相合并，记为第三水相，共908mL，后3次水洗所得水相用于下一批次三氯蔗糖制备过程中所述第一酯相的水洗步骤中套用。采用908mL乙酸丁酯萃取所述第三水相1次，得到932mL乙酸丁酯相，用于下一批次萃取第一水相，萃余水相记为第四水相，作为废水进行处理，所述第四水相中四氯蔗糖含量为0.2g/L。将所述第二酯相浓缩至干，回收乙酸丁酯，浓缩过程中加纯水助脱溶，最后将所得剩余物用纯水定容至1000mL，得到四氯蔗糖水溶液，所述四氯蔗糖水溶液中四氯蔗糖含量为167.89g/L，乙酸丁酯含量为0.06g/L。
(4)碱解步骤：将步骤(3)所得四氯蔗糖水溶液1000mL降温至10℃，滴加浓度为25wt％的四丁基氢氧化铵水溶液，滴加过程中控制体系温度为10℃，至体系pH值为12.5时停止滴加，之后保温反应1h；反应结束后所得产物体系中四氯蔗糖含量为0.3g/L，向所述产物体系中滴加浓度为35wt％的盐酸至体系pH值为6，得到1472mL三氯蔗糖粗产物水溶液。将所述三氯蔗糖粗产物水溶液浓缩至干，浓缩过程中加甲醇共沸，然后将所得剩余物用甲醇定容至7360mL，此时四丁基氯化铵从体系中析 出，抽滤分离；将滤液浓缩至干，回收甲醇，浓缩过程中加纯水与甲醇共沸，确保甲醇低残留，最后将所得剩余物用纯水定容至1472mL，得到三氯蔗糖水溶液，所述三氯蔗糖水溶液中甲醇含量0.2g/L，三氯蔗糖含量为95.99g/L，三氯蔗糖收率为60.8％。
实施例3
按照图1所示的工艺流程图制备三氯蔗糖，具体步骤如下：
(1)脱水步骤：在三口烧瓶中依次加入200g蔗糖和1000mL N,N-二甲基甲酰胺(DMF)，加热至70℃完全溶解，然后保持温度为70℃，抽真空至真空度为-0.1MPa(仪表压力)，进行脱水，当冷凝收集的DMF中水含量为0.20wt％时，脱水完毕，得到蔗糖定容液796mL，所述蔗糖定容液中蔗糖含量为251.01g/L。
(2)氯化反应步骤：在三口烧瓶中加入1065mL三氯乙烷，向所述三氯乙烷中滴加213mL氯化亚砜，滴加过程中控制体系温度为5℃；氯化亚砜滴加完毕后，再滴加步骤(1)所得蔗糖定容液796mL；蔗糖定容液滴加完毕后，依次升温至20℃保温反应0.5h、升温至45℃保温反应0.5h、升温至85℃保温反应1h、升温至110℃保温反应1.5h；反应结束后，将所得产物体系降温至5℃，在搅拌条件下滴加浓度为20wt％的氨水，将体系pH值调节至11后反应0.5h，之后用浓度为35wt％的盐酸将所得产物体系pH值调节至8，得到氯化中和液2360mL。
(3)分离步骤：将步骤(2)所得氯化中和液2360mL浓缩至干，回收DMF和三氯乙烷，浓缩过程中加纯水助脱溶，最后将所得剩余物用纯水定容至1000mL，得到第一水相，所述第一水相中DMF含量为3.91g/L，三氯乙烷含量为0.42g/L。在室温(25℃)条件下，采用乙酸丁酯萃取所述第一水相4次，每次萃取所用乙酸丁酯的体积为2000mL，萃取过程中将前2次萃取所得酯相合并，记为第一酯相，共4193mL，后2次萃取所得酯相用于下一批次三氯蔗糖制备过程中第一水相的乙酸丁酯萃取步骤中；萃余水相记为第二水相，共685mL，作为废水进行处理，所述第二水相中四氯蔗糖含量为0.1g/L。向所述第一酯相中加入4.19g活性炭进行脱色，之后过滤去除活性炭，采用纯水梯度水洗脱色后的第一酯相4次，每次水洗所用纯水的体积为630mL，得到4157mL第二酯相，纯水洗涤 过程中将前2次水洗所得水相合并，记为第三水相，共1321mL，后2次水洗所得水相用于下一批次三氯蔗糖制备过程中所述第一酯相的水洗步骤中。采用2642mL乙酸丁酯萃取所述第三水相1次，得到2670mL乙酸丁酯相，用于下一批次萃取第一水相，萃余水相记为第四水相，作为废水进行处理，所述第四水相中四氯蔗糖含量为0.1g/L。将所述第二酯相浓缩至干，回收乙酸丁酯，浓缩过程中加纯水助脱溶，最后将所得剩余物用纯水定容至1000mL，得到四氯蔗糖水溶液，所述四氯蔗糖水溶液中四氯蔗糖含量为170.26g/L，乙酸丁酯含量为0.05g/L。
(4)碱解步骤：将步骤(3)所得四氯蔗糖水溶液1000mL降温至5℃，滴加浓度为10wt％的四甲基氢氧化铵水溶液，滴加过程中控制体系温度为5℃，至体系pH值为10.5时停止滴加，之后保温反应4h；反应结束后所得产物体系中四氯蔗糖含量为0.4g/L，向所述产物体系中滴加浓度为35wt％的盐酸至体系pH值为7，得到1457mL三氯蔗糖粗产物水溶液。将所述三氯蔗糖粗产物水溶液浓缩至干，浓缩过程中加甲醇共沸，然后将所得剩余物用甲醇定容至8742mL，此时四甲基氯化铵从体系中析出，抽滤分离；将滤液浓缩至干，回收甲醇，浓缩过程中加纯水与甲醇共沸，确保甲醇低残留，最后将所得剩余物用纯水定容至1457mL，得到三氯蔗糖水溶液，所述三氯蔗糖水溶液中甲醇含量0.1g/L，三氯蔗糖含量为100.50g/L，三氯蔗糖收率为63.0％。
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 (26)

  1. 一种三氯蔗糖的制备方法，其特征在于，包括以下步骤：
    将蔗糖、N,N-二甲基甲酰胺、三氯乙烷与氯化亚砜混合，进行氯化反应，得到氯化产物料液；将所述氯化产物料液的pH值调节至碱性，进行分解反应，得到四氯蔗糖；
    将所述四氯蔗糖、水与碱解剂混合，进行碱解反应，得到三氯蔗糖。
  2. 根据权利要求1所述的制备方法，其特征在于，所述蔗糖、N,N-二甲基甲酰胺、三氯乙烷与氯化亚砜混合包括：将蔗糖与N,N-二甲基甲酰胺混合，得到蔗糖定容液；向所述三氯乙烷中依次滴加所述氯化亚砜与所述蔗糖定容液。
  3. 根据权利要求2所述的制备方法，其特征在于，所述蔗糖定容液使用前还包括真空脱水处理，所述真空脱水处理的温度为50～70℃，真空度为-0.1MPa；所述真空脱水处理在冷凝收集的N,N-二甲基甲酰胺中水含量＜0.3wt％时结束。
  4. 根据权利要求2所述的制备方法，其特征在于，滴加所述氯化亚砜与所述蔗糖定容液在-5～5℃条件下进行。
  5. 根据权利要求1～4任一项所述的制备方法，其特征在于，所述蔗糖与N,N-二甲基甲酰胺的用量比为1g：(3～5)mL；所述蔗糖与氯化亚砜的摩尔比为1：(5～10)；所述氯化亚砜与三氯乙烷的体积比为1：(4～5)。
  6. 根据权利要求1所述的制备方法，其特征在于，所述氯化反应包括依次进行第一阶段保温反应、第一升温、第二阶段保温反应、第二升温、第三阶段保温反应、第三升温和第四阶段保温反应；所述第一阶段保温反应的温度为10～20℃，保温时间为0.5～1h；所述第二阶段保温反应的温度为35～45℃，保温时间为0.5～1h；所述第三阶段保温反应的温度为75～85℃，保温时间为1～1.5h；所述第四阶段保温反应的温度为100～110℃，保温时间为1.5～2h。
  7. 根据权利要求1所述的制备方法，其特征在于，调节所述氯化产物料液的pH值至碱性在0～10℃条件下进行；所述碱性为pH＝9～11。
  8. 根据权利要求7所述的制备方法，其特征在于，调节所述氯化产 物料液pH值所用试剂为无机碱溶液。
  9. 根据权利要求8所述的制备方法，其特征在于，所述无机碱溶液包括氨水、NaOH溶液或KOH溶液，所述无机碱溶液的浓度为15～30wt％。
  10. 根据权利要求1所述的制备方法，其特征在于，所述分解反应的温度为0～10℃，保温时间为0.5～1h。
  11. 根据权利要求1和7～10任一项所述的制备方法，其特征在于，所述分解反应后还包括：
    将分解反应所得分解产物料液的pH值调节至6～8，得到氯化中和液；
    将所述氯化中和液进行分离纯化，得到四氯蔗糖。
  12. 根据权利要求11所述的制备方法，其特征在于，调节所述分解产物料液pH值所用试剂为无机酸。
  13. 根据权利要求12所述的制备方法，其特征在于，所述无机酸为盐酸；所述无机酸的浓度为35wt％。
  14. 根据权利要求11所述的制备方法，其特征在于，所述分离纯化包括：
    将所述氯化中和液浓缩至干，将剩余物与水混合，得到第一水相；
    采用乙酸丁酯对所述第一水相进行萃取，得到第一酯相；
    将所述第一酯相依次进行脱色和水洗，得到第二酯相；
    将所述第二酯相浓缩至干，得到四氯蔗糖。
  15. 根据权利要求14所述的制备方法，其特征在于，所述第一水相中N,N-二甲基甲酰胺的含量＜5g/L，三氯乙烷的含量＜1g/L。
  16. 根据权利要求14所述的制备方法，其特征在于，所述萃取的次数为4～6次，每次萃取所用乙酸丁酯与第一水相体积比为(0.5～2)：1。
  17. 根据权利要求15或16所述的制备方法，其特征在于，所述萃取还得到第二水相，所述萃取以使所述第二水相中四氯蔗糖的含量＜0.5g/L为基准。
  18. 根据权利要求14所述的制备方法，其特征在于，所述脱色所用材料为活性炭，所述活性炭的质量与第一酯相的体积比为(0.1～0.3)g：100mL。
  19. 根据权利要求14所述的制备方法，其特征在于，所述水洗的次 数为4～6次，每次水洗所用水与第一酯相的体积比为(0.1～0.2)：1。
  20. 根据权利要求14或19所述的制备方法，其特征在于，所述水洗还得到第三水相；得到所述第三水相后还包括：采用乙酸丁酯对所述第三水相进行萃取，得到乙酸丁酯相，所述乙酸丁酯相回用于对下一批次第一水相进行萃取。
  21. 根据权利要求20所述的制备方法，其特征在于，采用乙酸丁酯对所述第三水相进行萃取的次数为1～2次，每次萃取所用乙酸丁酯与第三水相的体积比为(0.5～2)：1；
    采用乙酸丁酯对所述第三水相进行萃取还得到第四水相，所述萃取以使所述第四水相中四氯蔗糖的含量＜0.5g/L为基准。
  22. 根据权利要求1所述的制备方法，其特征在于，所述碱解剂包括四甲基氢氧化铵水溶液、四乙基氢氧化铵水溶液或四丁基氢氧化铵水溶液；所述碱解剂的浓度为10或25wt％。
  23. 根据权利要求1或22所述的制备方法，其特征在于，所述碱解反应的条件包括：pH值为10.5～12.5，温度为0～10℃，保温时间为1～4h。
  24. 根据权利要求1所述的制备方法，其特征在于，所述碱解反应后还包括：
    采用盐酸将碱解反应所得碱解产物料液的pH值调节至6～8，得到三氯蔗糖粗产物水溶液；
    将所述三氯蔗糖粗产物水溶液浓缩至干，将剩余物溶解于甲醇中，析出氯盐后经固液分离，将所得滤液浓缩至干，将剩余物溶解于水中，得到含三氯蔗糖的水溶液。
  25. 根据权利要求24所述的制备方法，其特征在于，所述甲醇的体积为三氯蔗糖粗产物水溶液体积的4～6倍。
  26. 根据权利要求24或25所述的制备方法，其特征在于，所述含三氯蔗糖的水溶液中甲醇的含量＜0.3g/L。
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CN1800194A (zh) * 2006-01-12 2006-07-12 上海迪赛诺维生素有限公司 一种三氯蔗糖的合成方法
CN101619083A (zh) * 2009-06-19 2010-01-06 盐城捷康三氯蔗糖制造有限公司 工业生产三氯蔗糖-6-乙酸酯的氯化方法
US20120184729A1 (en) * 2011-01-19 2012-07-19 Liang Hengbo Method for preparing sucralose with high yield
CN113150047A (zh) * 2021-04-26 2021-07-23 南通市常海食品添加剂有限公司 一种三氯蔗糖-6-乙酸酯分离提取方法
WO2022140931A1 (zh) * 2020-12-28 2022-07-07 安徽金禾实业股份有限公司 蔗糖-6-羧酸酯的氯代方法

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CN1800194A (zh) * 2006-01-12 2006-07-12 上海迪赛诺维生素有限公司 一种三氯蔗糖的合成方法
CN101619083A (zh) * 2009-06-19 2010-01-06 盐城捷康三氯蔗糖制造有限公司 工业生产三氯蔗糖-6-乙酸酯的氯化方法
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