CN115956082A - Method for preparing sucralose crude product by using hydrolysis system - Google Patents
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- CN115956082A CN115956082A CN202280004529.3A CN202280004529A CN115956082A CN 115956082 A CN115956082 A CN 115956082A CN 202280004529 A CN202280004529 A CN 202280004529A CN 115956082 A CN115956082 A CN 115956082A
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- sucralose
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- 239000004376 Sucralose Substances 0.000 title claims abstract description 225
- 235000019408 sucralose Nutrition 0.000 title claims abstract description 225
- BAQAVOSOZGMPRM-QBMZZYIRSA-N sucralose Chemical compound O[C@@H]1[C@@H](O)[C@@H](Cl)[C@@H](CO)O[C@@H]1O[C@@]1(CCl)[C@@H](O)[C@H](O)[C@@H](CCl)O1 BAQAVOSOZGMPRM-QBMZZYIRSA-N 0.000 title claims abstract description 205
- 238000000034 method Methods 0.000 title claims abstract description 80
- 239000012043 crude product Substances 0.000 title claims abstract description 56
- 230000007062 hydrolysis Effects 0.000 title claims description 10
- 238000006460 hydrolysis reaction Methods 0.000 title claims description 10
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims abstract description 442
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 263
- FACOTAQCKSDLDE-YKEUTPDRSA-N [(2R,3R,4R,5R,6R)-6-[(2R,3S,4S,5S)-2,5-bis(chloromethyl)-3,4-dihydroxyoxolan-2-yl]oxy-3-chloro-4,5-dihydroxyoxan-2-yl]methyl acetate Chemical compound O[C@@H]1[C@@H](O)[C@@H](Cl)[C@@H](COC(=O)C)O[C@@H]1O[C@@]1(CCl)[C@@H](O)[C@H](O)[C@@H](CCl)O1 FACOTAQCKSDLDE-YKEUTPDRSA-N 0.000 claims abstract description 84
- 238000005904 alkaline hydrolysis reaction Methods 0.000 claims abstract description 58
- 238000000605 extraction Methods 0.000 claims abstract description 55
- 239000002994 raw material Substances 0.000 claims abstract description 42
- 239000000243 solution Substances 0.000 claims abstract description 42
- 239000007864 aqueous solution Substances 0.000 claims abstract description 38
- -1 sucralose diester Chemical class 0.000 claims abstract description 24
- 235000000346 sugar Nutrition 0.000 claims abstract description 13
- 150000008044 alkali metal hydroxides Chemical class 0.000 claims abstract description 10
- 239000012071 phase Substances 0.000 claims description 348
- 125000004494 ethyl ester group Chemical group 0.000 claims description 118
- 238000005406 washing Methods 0.000 claims description 110
- 238000003810 ethyl acetate extraction Methods 0.000 claims description 72
- 239000008346 aqueous phase Substances 0.000 claims description 57
- 238000002360 preparation method Methods 0.000 claims description 50
- 239000012141 concentrate Substances 0.000 claims description 39
- 238000002425 crystallisation Methods 0.000 claims description 35
- 230000008025 crystallization Effects 0.000 claims description 35
- 150000002148 esters Chemical class 0.000 claims description 29
- 239000007788 liquid Substances 0.000 claims description 23
- 238000002156 mixing Methods 0.000 claims description 16
- 238000001914 filtration Methods 0.000 claims description 15
- 238000006243 chemical reaction Methods 0.000 claims description 11
- 125000004177 diethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 6
- 230000003472 neutralizing effect Effects 0.000 claims description 5
- 230000018044 dehydration Effects 0.000 claims description 4
- 238000006297 dehydration reaction Methods 0.000 claims description 4
- 239000012535 impurity Substances 0.000 abstract description 39
- 239000002904 solvent Substances 0.000 abstract description 9
- 238000000926 separation method Methods 0.000 abstract description 6
- 238000003889 chemical engineering Methods 0.000 abstract description 2
- 239000012847 fine chemical Substances 0.000 abstract description 2
- 238000004939 coking Methods 0.000 abstract 1
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 37
- 239000000047 product Substances 0.000 description 28
- 238000001035 drying Methods 0.000 description 16
- 238000004064 recycling Methods 0.000 description 15
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 12
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 12
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 11
- 239000000203 mixture Substances 0.000 description 11
- 238000004519 manufacturing process Methods 0.000 description 10
- 238000006386 neutralization reaction Methods 0.000 description 10
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 9
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 9
- 238000000746 purification Methods 0.000 description 8
- 229930006000 Sucrose Natural products 0.000 description 7
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 7
- 239000005720 sucrose Substances 0.000 description 7
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 6
- WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 6
- 238000005660 chlorination reaction Methods 0.000 description 6
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 5
- 238000006136 alcoholysis reaction Methods 0.000 description 5
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 4
- 239000006227 byproduct Substances 0.000 description 4
- 239000003054 catalyst Substances 0.000 description 4
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 4
- CBENFWSGALASAD-UHFFFAOYSA-N Ozone Chemical compound [O-][O+]=O CBENFWSGALASAD-UHFFFAOYSA-N 0.000 description 3
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 3
- 229910052783 alkali metal Inorganic materials 0.000 description 3
- 150000001340 alkali metals Chemical class 0.000 description 3
- 239000003795 chemical substances by application Substances 0.000 description 3
- 230000004048 modification Effects 0.000 description 3
- 238000012986 modification Methods 0.000 description 3
- 230000003647 oxidation Effects 0.000 description 3
- 238000007254 oxidation reaction Methods 0.000 description 3
- 239000000126 substance Substances 0.000 description 3
- UOCLXMDMGBRAIB-UHFFFAOYSA-N 1,1,1-trichloroethane Chemical compound CC(Cl)(Cl)Cl UOCLXMDMGBRAIB-UHFFFAOYSA-N 0.000 description 2
- MIDXCONKKJTLDX-UHFFFAOYSA-N 3,5-dimethylcyclopentane-1,2-dione Chemical compound CC1CC(C)C(=O)C1=O MIDXCONKKJTLDX-UHFFFAOYSA-N 0.000 description 2
- 239000002253 acid Substances 0.000 description 2
- 229910021529 ammonia Inorganic materials 0.000 description 2
- 235000013736 caramel Nutrition 0.000 description 2
- 239000007795 chemical reaction product Substances 0.000 description 2
- 238000010586 diagram Methods 0.000 description 2
- ZPWVASYFFYYZEW-UHFFFAOYSA-L dipotassium hydrogen phosphate Chemical compound [K+].[K+].OP([O-])([O-])=O ZPWVASYFFYYZEW-UHFFFAOYSA-L 0.000 description 2
- 230000009977 dual effect Effects 0.000 description 2
- 238000005886 esterification reaction Methods 0.000 description 2
- JEGUKCSWCFPDGT-UHFFFAOYSA-N h2o hydrate Chemical compound O.O JEGUKCSWCFPDGT-UHFFFAOYSA-N 0.000 description 2
- 238000010438 heat treatment Methods 0.000 description 2
- 239000004615 ingredient Substances 0.000 description 2
- 238000009270 solid waste treatment Methods 0.000 description 2
- 238000003756 stirring Methods 0.000 description 2
- 238000000967 suction filtration Methods 0.000 description 2
- 238000004065 wastewater treatment Methods 0.000 description 2
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 1
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
- 208000024172 Cardiovascular disease Diseases 0.000 description 1
- YGYAWVDWMABLBF-UHFFFAOYSA-N Phosgene Chemical compound ClC(Cl)=O YGYAWVDWMABLBF-UHFFFAOYSA-N 0.000 description 1
- 230000002411 adverse Effects 0.000 description 1
- 239000003513 alkali Substances 0.000 description 1
- 235000011114 ammonium hydroxide Nutrition 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 235000013361 beverage Nutrition 0.000 description 1
- 208000026106 cerebrovascular disease Diseases 0.000 description 1
- 239000012295 chemical reaction liquid Substances 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 239000012320 chlorinating reagent Substances 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 235000021551 crystal sugar Nutrition 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 230000002526 effect on cardiovascular system Effects 0.000 description 1
- 230000007613 environmental effect Effects 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 238000001704 evaporation Methods 0.000 description 1
- 238000010812 external standard method Methods 0.000 description 1
- 235000013305 food Nutrition 0.000 description 1
- 235000003599 food sweetener Nutrition 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- 238000004128 high performance liquid chromatography Methods 0.000 description 1
- 230000004060 metabolic process Effects 0.000 description 1
- 239000012074 organic phase Substances 0.000 description 1
- 238000005191 phase separation Methods 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 239000000376 reactant Substances 0.000 description 1
- 238000001448 refractive index detection Methods 0.000 description 1
- 238000004904 shortening Methods 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 239000003765 sweetening agent Substances 0.000 description 1
- 229910021642 ultra pure water Inorganic materials 0.000 description 1
- 239000012498 ultrapure water Substances 0.000 description 1
- 239000011345 viscous material Substances 0.000 description 1
- 239000002699 waste material Substances 0.000 description 1
- 239000002351 wastewater Substances 0.000 description 1
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
- C07H1/00—Processes for the preparation of sugar derivatives
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
- C07H5/00—Compounds containing saccharide radicals in which the hetero bonds to oxygen have been replaced by the same number of hetero bonds to halogen, nitrogen, sulfur, selenium, or tellurium
- C07H5/02—Compounds containing saccharide radicals in which the hetero bonds to oxygen have been replaced by the same number of hetero bonds to halogen, nitrogen, sulfur, selenium, or tellurium to halogen
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
- Y02P20/00—Technologies relating to chemical industry
- Y02P20/10—Process efficiency
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Engineering & Computer Science (AREA)
- Biochemistry (AREA)
- Biotechnology (AREA)
- General Health & Medical Sciences (AREA)
- Genetics & Genomics (AREA)
- Molecular Biology (AREA)
- Saccharide Compounds (AREA)
Abstract
The invention provides a method for preparing a sucralose crude product by using an alcohol-water alkaline hydrolysis system, and relates to the technical field of fine chemical engineering. The method takes the aqueous solution containing the sucralose-6-acetate, the sucralose diester and the tetrachlorosucrose-6-acetate as the raw material solution, and carries out alkaline hydrolysis in an alkali metal hydroxide and water system, so that the sucralose-6-acetate and the sucralose ester impurities (the sucralose diester and the tetrachlorosucrose-6-acetate) in the raw material solution can be converted into the sucralose, and the yield of the sucralose is obviously improved. The invention uses multiple concentration and multiple extraction-back extraction between ethyl acetate/water double solvent systems for separation, so that fat-soluble impurities and water-soluble impurities are balanced in the system, the phenomenon of sugar coking in the concentration process can be avoided, the sucralose is fully crystallized in the ethyl acetate, and the sucralose yield is improved.
Description
Technical Field
The invention relates to the technical field of fine chemical engineering, in particular to a method for preparing a sucralose crude product by using a hydrolysis system.
Background
Sucralose, commonly called sucralose, is white crystalline powder or granules in appearance, is a new generation sweetener using sucrose as a raw material, has the sweetness of 600 times of that of sucrose, has pure taste, does not participate in human metabolism, can be used as 'zero calorie' sugar for diabetics, patients with cardiovascular and cerebrovascular diseases and old people, has the characteristics of good stability, high safety and the like, and is widely applied to a plurality of fields of foods, beverages, daily chemicals, medicines and the like.
At present, the production process of sucralose mainly comprises the following five steps: (1) esterification reaction: carrying out esterification reaction by using sucrose as a raw material, N, N-Dimethylformamide (DMF) as a solvent, organotin as a catalyst and acetic anhydride as an acylating agent to obtain a reaction product of sucrose-6-ethyl ester; (2) chlorination reaction: taking sucrose-6-ethyl ester as a raw material, DMF and trichloroethane as solvents, and a Williams reagent or phosgene as a chlorinating agent to carry out chlorination reaction, wherein a reaction product is sucralose-6-acetate; (3) purifying sucralose-6-acetate: neutralizing a chlorination solution obtained by chlorination reaction by using liquid alkali or ammonia water, evaporating to recover DMF and trichloroethane, dissolving in water, and performing multi-stage separation and purification to obtain a sucralose-6-acetate pure product; (4) alcoholysis reaction: carrying out alcoholysis reaction by taking high-purity sucralose-6-acetate as a raw material, sodium methoxide as a catalyst and methanol as a solvent, and then reacting with the reactant to obtain sucralose; (5) separation and purification: and (3) carrying out desolventizing, impurity removing, crystallizing and drying on the sucralose-6-acetate solution obtained after alcoholysis to obtain a sucralose pure product.
In the alcoholysis process by taking sucralose-6-acetate as a raw material, high-purity (more than 99%) sucralose-6-acetate needs to be adopted and carried out under anhydrous conditions, because excessive impurities can seriously affect the subsequent purification of sucralose, and the existence of water can affect the ester exchange reaction of sucralose-6-ethyl ester, so that the sucralose-6-ethyl ester is hydrolyzed to generate acetic acid, the quality of the subsequent sucralose is affected, and the yield is reduced. For example, in Chinese patents CN113004345A, CN104004032A, CN112805291A, CN1814609A, CN101012250A, CN102321122A and CN112771059A, sucralose is prepared by alcoholysis reaction of high-purity sucralose-6-acetate serving as a raw material. However, sucralose-6-acetate is more lost during the purification process, which in turn results in a lower yield of sucralose.
Chinese patent CN113717237a discloses that neutralization solution containing sucralose-6-acetate is used as a raw material, ethyl acetate extraction is performed, ester phase containing sucralose-6-acetate is subjected to ozone oxidation to remove part of impurities, then alkaline hydrolysis is performed by using a sodium hydroxide/water system, and then purification is performed to obtain sucralose. Although this patent uses a neutralized solution containing sucralose-6-acetate as a raw material, the molar yield is 103.7 to 105.1%, ozone oxidation is required, and this adversely affects the environment and human body.
Disclosure of Invention
In view of the above, the present invention provides a method for preparing a sucralose crude product by using a hydrolysis system, and the method provided by the present invention has the advantages of high sucralose yield, safety and environmental protection.
In order to achieve the above object, the present invention provides the following technical solutions:
the invention provides a method for preparing a sucralose crude product by using a hydrolysis system, which comprises the following steps:
(1) Extracting the raw material liquid with ethyl acetate to obtain a first ethyl ester phase and a first water phase respectively; concentrating the first ethyl ester phase to obtain a first ethyl ester phase concentrate; the raw material liquid is an aqueous solution containing sucralose-6-acetate, sucralose diester and tetrachlorosucrose-6-acetate;
(2) Mixing and dissolving the first ethyl ester phase concentrate and water, and concentrating to obtain a sucralose-6-acetate aqueous solution;
(3) Mixing the sucralose-6-acetate aqueous solution with an alkali metal hydroxide for an alkaline hydrolysis reaction, neutralizing the obtained reaction solution, and then carrying out hot filtration to obtain a second water phase;
(4) Carrying out ethyl acetate extraction on the second water phase to respectively obtain a second ethyl ester phase and a third water phase;
(5) Washing the second diethyl ester phase with water to respectively obtain a fourth water phase and a third diethyl ester phase; the fourth aqueous phase is reused in step (2) for dissolving the first ethyl ester phase concentrate;
(6) Mixing the third ethyl ester phase with ethyl acetate, and carrying out azeotropic dehydration to obtain a third ethyl ester phase concentrate; mixing the third ester phase concentrate with ethyl acetate to obtain a fourth ester phase;
(7) Crystallizing the fourth ethyl ester phase to respectively obtain a sucralose crude product and a fifth ethyl ester phase;
(8) Washing the fifth ethyl ester phase with water to obtain a fifth water phase and a sixth ethyl ester phase respectively; the fifth aqueous phase is recycled to step (2) for dissolving the first ethyl ester phase concentrate.
Preferably, in the step (1), the temperature of the ethyl acetate extraction is 40-60 ℃, and the extraction times are 5-8; the volume ratio of the raw material liquid to ethyl acetate for single-time ethyl acetate extraction is 1:0.2 to 0.4.
Preferably, in step (1), the content of sucralose-6-acetate in the first aqueous phase is less than 0.1g/L.
Preferably, in the step (2), the content of the ethyl acetate in the sucralose-6-acetate aqueous solution is less than 0.5g/L.
Preferably, in the step (3), the pH value of the alkaline hydrolysis reaction is 11-13, the temperature is 0-10 ℃, and the time is 3-6 h.
Preferably, in the step (3), the temperature of the hot filtration is 45 to 70 ℃.
Preferably, in the step (4), the number of times of ethyl acetate extraction is 4-7; the volume ratio of the second water phase to the ethyl acetate used for single-time extraction is 1:1 to 3;
combining ethyl esters obtained by the 1 st to 2 nd times of ethyl acetate extraction to obtain a second ethyl ester phase;
and (3) using the ethyl acetate phase obtained by the ethyl acetate extraction of the 3 rd to 7 th times for the ethyl acetate extraction of the second water phase in the preparation process of the crude sucralose product of the next time.
Preferably, in step (4), the third aqueous phase has a sucralose content of <0.5g/L.
Preferably, in the step (5), the number of times of water washing is 3 to 5; the volume ratio of the second diethyl phase to the single-use water for water washing is 1:0.1 to 0.3;
taking the water phase obtained by the 1 st water washing as a fourth water phase;
and (3) using the water phase obtained by the 2 nd-5 th water washing for the water washing of the second ethyl ester phase in the next sucralose crude product preparation process.
Preferably, in step (5), the third aqueous phase has a sucralose content of <0.5g/L.
Preferably, in step (6), the water content of the concentrate of the third ester phase is <0.5 wt%.
Preferably, in the step (6), the sugar degree of the fourth ethyl ester phase is 40 to 60%.
Preferably, in the step (7), the crystallization temperature is 40-60 ℃ and the time is 12-30 h.
Preferably, in the step (8), the content of sucralose in the sixth ethyl ester phase is less than 0.1g/L.
The invention provides a method for preparing a sucralose crude product by using a hydrolysis system. The method provided by the invention has the advantages that alkaline hydrolysis is carried out in an alkali metal hydroxide-water system, the sucralose-6-acetate, the sucralose diester and the tetrachlorosucrose-6-acetate are subjected to alkaline hydrolysis in the presence of a strong alkaline water solution to generate corresponding sucralose and tetrachlorosucrose, tetrachlorosucrose can be continuously dechlorinated in the presence of a strong alkaline water solution to form sucralose, and the sucralose-6-acetate and impurities (the sucralose diester and the tetrachlorosucrose-6-acetate) in a raw material liquid are converted into sucralose, so that the raw material conversion rate and the sucralose yield are remarkably improved. The invention adopts a dual system of ethyl acetate and water, can realize the mutual indiscriminate application and extraction impurity removal between the dual systems, and enrich the sucralose, thereby leading the sucralose to be capable of crystallizing in the ethyl acetate in a large amount, and recycling the sucralose by a repeated indiscriminate application way, avoiding the loss of the sucralose and greatly improving the overall yield of the sucralose. In addition, the method carries out alkaline hydrolysis in an alkali metal hydroxide-water system, not only can replace the traditional sodium methoxide/methanol reaction system with higher hazard, but also can omit the purification of the sucralose-6-acetate before the alkaline hydrolysis, and does not need ozone oxidation, thereby greatly shortening the flow, and being safe and environment-friendly.
Drawings
FIG. 1 is a process flow diagram for preparing sucralose crude product using a hydrolysis system;
FIG. 2 is a detailed process flow diagram for preparing crude sucralose by using a hydrolysis system.
Detailed Description
The invention is further illustrated below with reference to examples and figures.
The invention provides a method for preparing a sucralose crude product by using a hydrolysis system, which comprises the following steps:
(1) Extracting the raw material liquid by ethyl acetate to respectively obtain a first ethyl ester phase and a first water phase; concentrating the first ethyl ester phase to obtain a first ethyl ester phase concentrate; the raw material liquid is an aqueous solution containing sucralose-6-acetate, sucralose diester and tetrachlorosucrose-6-acetate;
(2) Mixing and dissolving the first ethyl ester phase concentrate and water, and concentrating to obtain a sucralose-6-acetate aqueous solution;
(3) Mixing the sucralose-6-acetate aqueous solution with an alkali metal hydroxide for an alkaline hydrolysis reaction, neutralizing the obtained reaction solution, and then carrying out hot filtration to obtain a second water phase;
(4) Carrying out ethyl acetate extraction on the second water phase to respectively obtain a second ethyl ester phase and a third water phase;
(5) Washing the second ethyl ester phase with water to respectively obtain a fourth water phase and a third ethyl ester phase; the fourth aqueous phase is reused in step (2) for dissolving the first ethyl ester phase concentrate;
(6) Mixing the third ethyl ester phase with ethyl acetate, and carrying out azeotropic dehydration to obtain a third ethyl ester phase concentrate; mixing the third ester phase concentrate with ethyl acetate to obtain a fourth ester phase;
(7) Crystallizing the fourth ethyl ester phase to respectively obtain a sucralose crude product and a fifth ethyl ester phase;
(8) Washing the fifth ethyl ester phase with water to obtain a fifth water phase and a sixth ethyl ester phase respectively; the fifth aqueous phase is recycled to step (2) for dissolving the first ethyl ester phase concentrate.
In the present invention, all the raw material components are commercially available products well known to those skilled in the art unless otherwise specified.
Extracting raw material liquid by ethyl acetate to respectively obtain a first ethyl ester phase and a first water phase; concentrating the first ethyl ester phase to obtain a first ethyl ester phase concentrate; the raw material liquid is an aqueous solution containing sucralose-6-acetate, sucralose diester and tetrachlorosucrose-6-acetate.
The preparation method of the raw material solution is not particularly limited, and a preparation method for preparing a crude sucrose-6-acetate product by taking sucrose as an initial raw material, which is well known to those skilled in the art, is adopted, and the preparation method specifically comprises the following steps: preparing a solution containing sucrose-6-acetate by taking sucrose as a raw material, N, N-Dimethylformamide (DMF) as a solvent, organotin as a catalyst and acetic anhydride as an acylating agent; and then sequentially carrying out chlorination (thionyl chloride) and ammonia neutralization on the obtained solution containing the sucrose-6-acetate, carrying out vacuum concentration until the solution is dry, and adding water for dissolving to obtain a raw material solution.
In the present invention, the content of sucralose-6-acetate in the raw material solution is preferably 50 to 80g/L, and more preferably 50 to 75g/L; the mass ratio of the sucralose-6-acetate, the sucralose diester and the tetrachlorosucrose-6-acetate in the raw material liquid is preferably 1: 0.06-0.15: 0.06 to 0.15, more preferably 1: 0.08-0.1: 0.09 to 0.13; the raw material liquid preferably further comprises NH 4 Cl and organic impurities, said NH 4 The concentration of Cl is preferably 80-150 g/L, and more preferably 84-140 g/L; the concentration of the organic impurities is preferably 30 to 80g/L, more preferably 32 to 73g/L.
In the invention, the temperature of the ethyl acetate extraction is preferably 40-60 ℃, more preferably 45-55 ℃, and further preferably 50 ℃; the invention has no special limitation on the extraction frequency of the ethyl acetate, and the content of the sucralose-6-acetate in the water phase (namely the first water phase) obtained by the last extraction of the ethyl acetate is less than 0.1g/L, specifically 5-8 times; the time for single ethyl acetate extraction is preferably 10-30 min, and more preferably 15-25 min; the volume ratio of the raw material liquid to ethyl acetate for single ethyl acetate extraction is preferably 1:0.2 to 0.5, more preferably 1:0.3 to 0.4. In the invention, ethyl ester phases obtained by ethyl acetate extraction are combined into a first ethyl ester phase, and a raffinate phase obtained by the last ethyl acetate extraction is a first water phase, wherein the first water phase is preferably subjected to high-salt wastewater treatment.
According to the invention, hot ethyl acetate (40-60 ℃) is adopted to extract the raw material liquid, so that the using amount of the ethyl acetate can be reduced, and the dissolving amount of fat-soluble impurities is increased, thereby being beneficial to increasing the solubility of subsequent sucralose in the ethyl acetate, and further improving the crystal sugar degree and the sucralose crystallization yield.
The concentration method is not particularly limited in the present invention, and a concentration method known to those skilled in the art can be adopted, specifically, vacuum concentration is adopted, the concentration temperature is preferably 60-80 ℃, the vacuum degree is preferably-0.1-0.08 MPa (gauge pressure), the concentration time is not particularly limited in the present invention, and the concentration is carried out until the content of ethyl acetate in the obtained first ethyl ester phase concentrate is less than 0.5g/L. According to the method, the residual quantity of the ethyl acetate in the first ethyl acetate phase concentrate is controlled, so that byproducts such as acetic acid and ethanol generated by the ethyl acetate in the subsequent alkaline hydrolysis step can be avoided, and the purity and the yield of the sucralose are further improved.
After the first ethyl ester phase concentrate is obtained, the first ethyl ester phase concentrate is mixed with water for dissolving, and then the mixture is concentrated to obtain the sucralose-6-acetate aqueous solution. In the present invention, the volume ratio of the sucralose-6-acetate aqueous solution to the raw material liquid is preferably 1:0.5 to 1, more preferably 1:0.6 to 0.7. The concentration mode of the invention is not specially limited, and the concentration mode known by the technicians in the field can be adopted, specifically, the concentration is carried out in vacuum, the temperature of the concentration is preferably 60-80 ℃, the vacuum degree is preferably-0.1-0.08 MPa (gauge pressure), the time of the concentration is not specially limited, and the concentration is carried out until the content of the ethyl acetate in the obtained sucralose-6-acetate aqueous solution is less than 0.5g/L. According to the method, the residual quantity of the ethyl acetate in the sucralose-6-acetate aqueous solution is controlled, so that byproducts such as acetic acid and ethanol generated by the ethyl acetate in the subsequent alkaline hydrolysis step can be avoided, and the purity and the yield of the sucralose are further improved.
After the sucralose-6-acetate aqueous solution is obtained, the sucralose-6-acetate aqueous solution is mixed with an alkali metal hydroxide for carrying out an alkaline hydrolysis reaction, and the obtained reaction solution is neutralized and then is filtered thermally to obtain a second aqueous phase.
In the present invention, the alkali metal hydroxide preferably includes sodium hydroxide and/or potassium hydroxide; the alkali metal hydroxide is preferably used in the form of an aqueous alkali metal hydroxide solution, the concentration of which is preferably 10 to 40wt%, more preferably 20 to 35wt%; the dosage of the alkali metal hydroxide is not particularly limited, and the pH value in the alkaline hydrolysis reaction process can be ensured to be 11-13, more preferably 11.5-12.5, and further preferably 12; the temperature of the alkaline hydrolysis reaction is preferably 0-10 ℃, more preferably 0-8 ℃, and further preferably 1-5 ℃; the time for the alkaline hydrolysis reaction is preferably 3 to 6 hours, more preferably 3.5 to 5.5 hours, and still more preferably 4 to 5 hours. The invention carries out the alkaline hydrolysis reaction under the conditions, the sucralose diester can be hydrolyzed to generate sucralose, the tetrachlorosucrose-6-acetate can be dechlorinated and hydrolyzed to generate sucralose, and by-products generated by overhigh pH value of the alkaline hydrolysis reaction or overhigh temperature of the alkaline hydrolysis reaction can be avoided. Compared with the method using pure sucralose-6-acetate as a raw material, the method has the advantages that the yield of the sucralose is obviously improved, and the crude sucralose-6-acetate aqueous solution is not required to be purified, so that the process flow is greatly shortened, and the production cost is reduced.
In the present invention, the acid for neutralization preferably includes hydrochloric acid, and the concentration of the hydrochloric acid is preferably 15 to 35wt%, more preferably 20 to 30wt%. The amount of the acid used in the present invention is not particularly limited, and the system may be neutralized to a pH of 6.8 to 7.
In the present invention, the temperature of the hot filtration is preferably 45 to 70 ℃, more preferably 50 to 70 ℃. The method provided by the invention can be used for neutralizing the reaction liquid obtained by alkaline hydrolysis reaction and then heating to 45-70 ℃, so that the sucralose mixed in the viscous substance can be dissolved, then carrying out thermal filtration can remove insoluble substances such as carbon residue and tar, and simultaneously avoiding the sucralose from being coked due to overhigh temperature.
After the second water phase is obtained, the second water phase is subjected to ethyl acetate extraction to respectively obtain a second ethyl ester phase and a third water phase. In the present invention, the number of times of the ethyl acetate extraction is preferably 4 to 7; the volume ratio of the second aqueous phase to the ethyl acetate used for the single extraction is preferably 1:1 to 3, more preferably 1.5 to 2.5; in the invention, the ethyl ester phase obtained by the extraction of the ethyl acetate for 1 to 2 times is preferably combined to be used as a second ethyl ester phase; preferably, the ethyl acetate phase obtained by the ethyl acetate extraction of the 3 rd to 7 th times is used for ethyl acetate extraction of the second aqueous phase in the next sucralose crude product preparation process, specifically, the ethyl acetate phase obtained by the ethyl acetate extraction of the 3 rd time is used for ethyl acetate extraction of the 1 st time of the second aqueous phase in the next sucralose crude product preparation process, the ethyl acetate phase obtained by the ethyl acetate extraction of the 4 th time is used for ethyl acetate extraction of the 2 nd time of the second aqueous phase in the next sucralose crude product preparation process, the ethyl acetate phase obtained by the ethyl acetate extraction of the 5 th time is used for ethyl acetate extraction of the 3 rd time of the second aqueous phase in the next sucralose crude product preparation process, the ethyl acetate phase obtained by the ethyl acetate extraction of the 6 th time is used for ethyl acetate extraction of the 4 th time of the second aqueous phase in the next sucralose crude product preparation process, the ethyl acetate phase obtained by the ethyl acetate extraction of the 7 th time is used for ethyl acetate extraction of the 5 th time of the second aqueous phase in the next sucralose crude product preparation process (that the ethyl acetate phase obtained by the ethyl acetate extraction of the 3 th to 7 th times is used for ethyl acetate extraction of the first aqueous phase of the second aqueous phase in the next sucralose crude product preparation process), and the ethyl acetate extraction of the next sucralose crude product is preferably used for ethyl acetate extraction of the 6 th time. In the present invention, the sucralose content in the third aqueous phase is preferably <0.5g/L.
After the second diethyl ester phase is obtained, the second diethyl ester phase is washed by water to respectively obtain a fourth water phase and a third diethyl ester phase; the fourth aqueous phase is recycled to step (2) for dissolving the first ethyl ester phase concentrate.
In the present invention, the number of times of the water washing is preferably 3 to 5 times; the volume ratio of the second diethyl ester phase to the water-washed single-use water is preferably 1:0.1 to 0.3, more preferably 1:0.1 to 0.25; in the invention, the water phase obtained by the 1 st water washing is preferably used as a fourth water phase, the water phase obtained by the 2 nd to 5 th water washing is preferably used for water washing of the second diethyl ester phase in the next sucralose crude product preparation process, specifically, the water phase obtained by the 2 nd water washing is used for the 1 st water washing of the second diethyl ester phase in the next sucralose crude product preparation process, the water phase obtained by the 3 rd water washing is used for the 2 nd water washing of the second diethyl ester phase in the next sucralose crude product preparation process, the water phase obtained by the 4 th water washing is used for the 3 rd water washing of the second diethyl ester phase in the next sucralose crude product preparation process, and the water phase obtained by the 5 th water washing is used for the 4 th water washing of the second diethyl ester phase in the next sucralose crude product preparation process (namely, the water phases obtained by the 2 nd to 5 th water washing are sequentially used for the 1 st to 4 th water washing of the second diethyl ester phase in the next sucralose crude product preparation process), and the 5 th water washing of the second diethyl ester phase of the next sucralose crude product is preferably used for pure water.
Mixing the third ethyl ester phase with ethyl acetate, and carrying out azeotropic dehydration to obtain a third ethyl ester phase concentrate; mixing the third ester phase concentrate with ethyl acetate to obtain a fourth ester phase. The present invention is not limited to the above-mentioned concentration method, and can adopt the concentration method known to those skilled in the art, such as vacuum concentration, and the present invention is not limited to the above-mentioned concentration condition, and can concentrate until the water content of said third ethyl ester phase concentrate is less than 0.5wt%. The amount of ethyl acetate used in the present invention is not particularly limited, and is more preferably 45 to 60% based on the sugar degree (Bx) of the fourth ethyl ester phase being 40 to 60%.
After the fourth ester phase is obtained, the fourth ester phase is crystallized to respectively obtain a sucralose crude product and a fifth ester phase. In the present invention, the temperature of the crystallization is preferably 40 to 60 ℃, more preferably 45 to 55 ℃; the crystallization time is preferably 12 to 35 hours, more preferably 20 to 34 hours. The solubility of the sucralose in the ethyl acetate is low, the fat-soluble caramel impurities in the system are introduced into the ethyl acetate in the recycling process of the fourth water phase and the fifth water phase, so that the solubility of the sucralose in the ethyl acetate can be obviously increased, and the impurities in the system are balanced by adopting the modes of extraction, water washing and recycling, so that the sucralose is enriched in the ethyl acetate and crystallized. Moreover, the crystallization of sucralose under the above temperature conditions has the following two advantages: firstly, more sucralose can be obtained without being mixed with more fat-soluble impurities; secondly, the sucralose is not coked due to higher crystallization temperature, thereby improving the yield of the sucralose.
After the crystallization is completed, the method preferably further comprises solid-liquid separation to obtain a sucralose crude product and a fifth ethyl ester phase respectively. In the present invention, the solid-liquid separation preferably includes filtration or suction filtration.
After a fifth ethyl ester phase is obtained, the fifth ethyl ester phase is washed by water to respectively obtain a fifth water phase and a sixth ethyl ester phase; the fifth aqueous phase is recycled to step (2) for dissolving the first ethyl ester phase concentrate. The number of times of the water washing is not particularly limited, and the content of the sucralose in the sixth ethyl ester phase obtained by the last water washing is less than 0.1g/L, specifically 4-8 times. The amount of the water used for washing is not particularly limited, and the amount of the water used for washing is known to those skilled in the art, and in the specific embodiment of the present invention, the volume ratio of the fifth ethyl ester phase to the water used for washing is preferably 1:0.4 to 0.6. In the invention, the sixth ethyl ester phase is preferably concentrated to obtain recovered ethyl acetate and sugar residues, and the sugar residues are preferably subjected to solid waste treatment. After crystallization is completed, fat-soluble impurities in the fifth ethyl ester phase are more, and the solubility of sucralose in water is higher.
The water-soluble impurities and the fat-soluble impurities are generated in a series of reaction processes of sucrose, so that the water-soluble impurities, the fat-soluble impurities and the sucralose have a similar main body structure, and the water-soluble impurities, the fat-soluble impurities and the sucralose have a certain mutual solubility. The invention uses the relationship between the three, and selects water and ethyl acetate as the solvent for removing water-soluble impurities and fat-soluble impurities, thereby using two solvents to dissolve and carry the sucralose, realizing the exchange of the sucralose in the two solvents, enriching the sucralose in the ethyl acetate, and crystallizing the sucralose to obtain the crude sucralose. Specifically, the solubility of sucralose in ethyl acetate is much less than that in water, so that the present invention retains more fat-soluble impurities in the system during pretreatment. After the alkaline hydrolysis reaction, the sucralose is extracted from the alkaline hydrolysis solution by adopting ethyl acetate for multiple times. At this time, the concentration of sucralose in the ethyl acetate obtained by multiple extractions shows a gradient decrease phenomenon, and the sucralose content in the ethyl acetate phase obtained by the previous two extractions is higher and is used as a raw material for sucralose crystallization. The remaining batch of ethyl acetate phase is used for extraction of the next batch of alkaline hydrolysis solution, so that a saturated ethyl sucralose acetate solution can be obtained. The water-soluble impurities content affects the crystallization of sucralose in the ethyl acetate phase, and thus the first two sucralose-containing ethyl acetate phases require a small amount of pure water for multiple water washes to remove the water-soluble impurities. And in order to recover part of the sucralose, the water washing liquid (fourth water phase) which is washed for the first time and has the highest sucralose concentration is recycled to be mixed and dissolved with the first ethyl ester phase concentrate, and the rest water washing liquid is used for washing the second ethyl ester phase of the sucralose in the next batch. The concentration and drying treatment of the obtained triethyl ester phase after washing with water aims to remove the water in the system, because the residual water can increase the crystallization difficulty of the sucralose in the ethyl acetate. After the concentration and the drying, fresh ethyl acetate is added to continue the concentration and the drying, in order to remove the water, at the moment, fresh ethyl acetate is used for dissolving the third ester concentrate to a specific sugar degree, and the obtained fourth ester phase can be crystallized to obtain the crude sucralose.
The technical solution of the present invention will be clearly and completely described below with reference to the embodiments of the present invention. It should be apparent that the described embodiments are only some embodiments of the present invention, and not all embodiments. All other embodiments, which can be obtained by a person skilled in the art without making any creative effort based on the embodiments in the present invention, belong to the protection scope of the present invention.
The content of each substance in each of the following examples was measured by High Performance Liquid Chromatography (HPLC) using an external standard method under the following conditions: a Japanese Shimadzu high performance liquid chromatograph, which is matched with RID-10A refractive index detection, an LC-10ADVP high-pressure pump and a CTO-10ASVP constant temperature box; a chromatographic column: agilentXDB C18 column (250 mm. Times.4.6 mm,5 μm); mobile phase: methanol-0.125 wt% aqueous dipotassium hydrogen phosphate solution (4; column temperature: at 40 ℃; flow rate of mobile phase: 1.0mL/min; wherein, the methanol (chromatographic purity), the dipotassium hydrogen phosphate (analytical purity) and the water are ultrapure water.
Method for preparing the starting material liquid (denoted as first aqueous solution) used in the following examples: using sucrose as a raw material, DMF as a solvent, organotin as a catalyst and acetic anhydride as an acylating agent to prepare a solution containing sucrose-6-acetate; and then sequentially carrying out chlorination (thionyl chloride) and ammonia neutralization on the obtained solution containing the sucrose-6-acetate, carrying out vacuum concentration to dryness, and adding water to dissolve to obtain a raw material solution.
Example 1
The process flow charts shown in fig. 1 and fig. 2 are adopted to prepare the sucralose crude product, and the specific steps are as follows:
(1) An extraction step: putting 1000mL of the first aqueous solution into a 2L eggplant-shaped bottle, adding 300mL of ethyl acetate, stirring and extracting for 15min at 50 ℃, carrying out phase separation to obtain an organic phase and a water phase, repeating the extraction step for 6 times on the water phase, combining the ester phases to obtain a first ethyl ester phase after the extraction is finished, and taking the water phase obtained in the last extraction as a first water phase (the content of sucralose-6-acetate is 0.08g/L, and the first water phase is subjected to high-salt wastewater treatment).
Wherein the composition of the first aqueous solution is shown in table 1:
TABLE 1 composition of the first aqueous solution
| Components | Content (wt.) |
| Sucralose-6-acetate | 52.0g/L |
| Sucralose diester | 4.7g/L |
| Tetrachlorosucrose-6-acetate | 5.7g/L |
| NH 4 Cl | 84.2g/L |
| Other organic impurities | 30.1g/L |
| Water (I) | 84.2％ |
(2) A concentration and drying step: the first ethyl ester phase is concentrated to dryness (abbreviated as concentrated dryness) in vacuum at 80 ℃ and-0.08 MPa, water is added into the obtained first ethyl ester phase concentrate to 1000mL, and the mixture is concentrated to 600mL under the above conditions to obtain an aqueous solution of sucralose-6-acetate (the content of ethyl acetate is 0.41 g/L), and then the aqueous solution is transferred to a 1000mL three-neck flask.
(3) An alkaline hydrolysis step: cooling the obtained sucralose-6-acetate aqueous solution to 1 ℃, then dropwise adding a 32wt% sodium hydroxide aqueous solution), uniformly mixing, carrying out alkaline hydrolysis at 1 ℃ for 5 hours, keeping the pH value of the system to be 12.3 in the alkaline hydrolysis process, dropwise adding 30wt% dilute hydrochloric acid after the alkaline hydrolysis is finished to neutralize to pH =7, heating to 50 ℃, and carrying out heat filtration to obtain a second water phase (650 mL, the content of the sucralose-6-acetate is 0.04 g/L) and filter residues (solid waste treatment);
(4) A separation step: adding 1.3L of ethyl acetate into the second aqueous phase, stirring and extracting for 15min at 50 ℃, repeating the extraction operation on the obtained aqueous phase for 6 times, combining ester phases obtained by the 1 st-2 th extraction to obtain a second ethyl ester phase (2.8L), and using the ethyl ester phase obtained by the 3 rd-6 th ethyl acetate extraction as the 1 st-4 th ethyl acetate extraction of the second aqueous phase in the preparation process of the next crude sucralose product. Adding 550mL of water into the second ethyl ester phase for water washing, wherein the water washing is carried out for 6 times, the water phase obtained by the 1 st water washing is a fourth water phase, and the fourth water phase is used for replacing water in the step (2) and is mixed with the first ethyl ester phase concentrate; and (3) washing the water phases obtained by the 2 nd to 6 th washing with water from the 1 st to 5 th washing of the second ester phase in the preparation process of the next batch of crude sucralose product in sequence, wherein the ester phase obtained after the washing with water is the third ester phase. And (3) concentrating and drying the third ester phase at 70 ℃ and under the condition of-0.1 MPa (gauge pressure), adding ethyl acetate (the adding times are 3 times, and each time 300 mL) in the concentrating and drying process to dehydrate so as to ensure that the water is completely removed, and adding ethyl acetate into the obtained third ester phase concentrate to adjust the sugar degree Bx to be 43% so as to obtain a fourth ester phase.
(5) A crystallization step: crystallizing the fourth ethyl ester phase at 45 ℃ for 24 hours, and performing suction filtration to respectively obtain a sucralose crude product and 420mL of a fifth ethyl ester phase (after 4 times of balance is applied); washing the fifth ethyl ester phase for 6 times (the water consumption is 210mL each time), wherein the ester phase after washing is a sixth ester phase (the content of sucralose is 0.03 g/L), and concentrating and drying the sixth ester phase to respectively obtain recovered ethyl acetate and sugar residues; the combined aqueous phases were used as a fifth aqueous phase which was used in step (2) instead of water to mix with the first ethyl ester phase concentrate.
(6) Recycling the fourth aqueous phase and the fifth aqueous phase 17 times according to the operations (recorded as recycling 0 time) of the steps (1) to (5), wherein "adding water to 1000mL in the obtained first ethyl ester phase concentrate" in the step (1) is modified to "mixing the obtained first ethyl ester phase, the fourth aqueous phase and the fifth aqueous phase"; in the step (4), the ethyl acetate extraction of the 1 st to 4 th times of the second water phase is performed by using the ethyl acetate phase obtained by the ethyl acetate extraction of the 3 rd to 6 th times of the second water phase in the preparation process of the previous batch of crude sucralose product, and the ethyl acetate extraction of the 5 th to 6 th times of the second water phase is performed by using pure ethyl acetate; the 1 st to 5 th water washing of the second diethyl ester phase utilizes the water phase obtained by the 2 nd to 6 th water washing of the second diethyl ester phase in the preparation process of the crude sucralose product of the previous batch, and the 6 th water washing of the second diethyl ester phase is carried out by pure water; the purity and yield data of the crude sucralose product are shown in table 2:
TABLE 2 sucralose crude product purity and yield
Note: yield = mass of sucralose/mass of sucralose-6-acetate completely converted to sucralose × 100%. In the first aqueous solution, both the sucralose diester and the tetrachlorosucrose-6-acetate can be converted into sucralose after alkaline hydrolysis, and the theoretical maximum yield in example 1 is 121.18%.
Example 2
The crude sucralose product is prepared according to the method in example 1, which is different from the method in example 1 in that:
in the step (1), the main components of the used first solution are shown in table 3, the volume of ethyl acetate for single extraction is 200mL, the extraction temperature is 60 ℃, the extraction time is 20min, the extraction step is repeated for 7 times for the aqueous phase, and the content of sucralose-6-acetate in the first aqueous phase is 0.05g/L;
TABLE 3 first solution Components Table
| Components | Content (wt.) |
| Sucralose-6-acetate | 65.0g/L |
| Sucralose diester | 5.1g/L |
| Tetrachlorosucrose-6-acetate | 6.0g/L |
| NH 4 Cl | 102.3g/L |
| Other organic impurities | 37.6g/L |
| Water (W) | 76.9％ |
In the step (2), the mixture is concentrated and dried under the conditions of 75 ℃ and-0.09 MPa, and the sucralose-6-acetate aqueous solution (650 mL, the content of ethyl acetate is 0.37 g/L);
in the step (3), the temperature is reduced to 3 ℃, the alkaline hydrolysis temperature is 3 ℃, the alkaline hydrolysis pH is =12.5, the alkaline hydrolysis time is 4h, the neutralization time is 6.9, the hot filtration temperature is 50 ℃, and a second aqueous phase (700 mL, the content of sucralose-6-acetate is 0.03 g/L);
in the step (4), 2100mL of ethyl acetate is added once, extraction is carried out for 5 times, the volume of the second ethyl acetate phase is 4250mL, the ethyl acetate phase obtained by the 3 rd-5 th time of ethyl acetate extraction is used as the 1 st-3 rd time of ethyl acetate extraction of the second water phase in the preparation process of the next batch of sucralose crude products, the washing frequency is 5 times, 425mL of water is used for washing once, the water phase obtained by the 2 nd-5 th time of water washing of the second ethyl acetate phase is sequentially washed by the 1 st-4 th time of the second ethyl acetate phase in the preparation process of the next batch of sucralose crude products, and the ethyl acetate phase is concentrated and dried under the conditions of 75 ℃ and 0.08MPa, the adding frequency of ethyl acetate is 4 times in the concentrating and drying process, the amount of ethyl acetate added once is 1000mL, and the Bx is 50%;
in the step (5), the crystallization temperature is 50 ℃, the crystallization time is 30h, the volume of the fifth ethyl ester phase is 400mL, the washing frequency is 7 times, the water consumption for single washing is 160mL, and the content of sucralose in the sixth ethyl ester phase is 0.04g/L;
in the step (6), the ethyl acetate extraction of the 1 st to 3 rd times of the second water phase is performed by using the ethyl acetate phase obtained by the ethyl acetate extraction of the 3 rd to 5 th times of the second water phase in the preparation process of the previous batch of crude sucralose product, and the ethyl acetate extraction of the 4 th to 5 th times of the second water phase is performed by using pure ethyl acetate; the 1 st to 4 th water washing of the second diethyl ester phase utilizes the water phase obtained by the 2 nd to 5 th water washing of the second diethyl ester phase in the preparation process of the crude sucralose of the previous batch, and the 5 th water washing of the second diethyl ester phase is carried out by pure water; the purity and yield data of the sucralose crude product obtained by recycling 17 times are shown in table 4:
TABLE 4 sucralose crude purity and yield
Note: theoretical maximum yield 115.72%.
Example 3
The crude sucralose product is prepared according to the method of example 1, which is different from example 1 in that:
in the step (1), the main components of the used first solution are shown in table 5, the volume of ethyl acetate for single extraction is 400mL, the extraction temperature is 40 ℃, the extraction time is 10min, the extraction step is repeated for 5 times for the aqueous phase, and the content of sucralose-6-acetate in the first aqueous phase is 0.02g/L;
TABLE 5 first solution Components Table
| Components | Content (wt.) |
| Sucralose-6-acetate | 50.0g/L |
| Sucralose diester | 5.2g/L |
| Tetrachlorosucrose-6-acetate | 6.3g/L |
| NH 4 Cl | 84.9g/L |
| Other organic impurities | 36.7g/L |
| Water (W) | 83.7％ |
In the step (2), the mixture is concentrated and dried under the conditions of 80 ℃ and-0.09 MPa, and sucralose-6-acetate aqueous solution (600 mL, the content of ethyl acetate is 0.23 g/L);
in the step (3), the temperature is reduced to 5 ℃, the alkaline hydrolysis temperature is 10 ℃, the alkaline hydrolysis pH =11.0, the alkaline hydrolysis time is 6h, the neutralization temperature is 70 ℃, the hot filtration temperature is 70 ℃, and a second aqueous phase (635 mL, the content of sucralose-6-acetate is 0.02 g/L);
in the step (4), 635mL of ethyl acetate is added once, extraction is carried out for 7 times, the volume of the second ethyl acetate phase is 680mL, the ethyl acetate phase obtained by 3-7 times of ethyl acetate extraction is used as the 1 st-5 th time of ethyl acetate extraction of the second water phase in the preparation process of the next batch of sucralose crude products, the washing frequency is 7 times, 68mL of water is used for washing once, the water phase obtained by 2-7 times of washing of the second ethyl ester phase is sequentially washed by the 1 st-6 th time of the second ethyl ester phase in the preparation process of the next batch of sucralose crude products, and then the ethyl acetate phase is concentrated under the conditions of 80 ℃ -0.08MPa, the adding frequency of ethyl acetate is 4 times in the concentrating process, the amount of ethyl acetate added once is 136mL, and the Bx is 40%;
in the step (5), the crystallization temperature is 40 ℃, the crystallization time is 36h, the volume of the fifth ethyl ester phase is 500mL, the washing frequency is 5 times, the water consumption for single washing is 200mL, and the content of sucralose in the sixth ethyl ester phase is 0.01g/L;
in the step (6), the ethyl acetate phase obtained by the ethyl acetate extraction of the second water phase from the 1 st to 5 th times in the preparation process of the crude sucralose product of the previous batch is used for the ethyl acetate extraction of the second water phase from the 3 rd to 7 th times, and the ethyl acetate extraction of the second water phase from the 6 th to 7 th times is carried out by using pure ethyl acetate; the 1 st to 6 th water washing of the second diethyl ester phase utilizes the water phase obtained by the 2 nd to 7 th water washing of the second diethyl ester phase in the preparation process of the crude sucralose product of the previous batch, and the 7 th water washing of the second diethyl ester phase is carried out by pure water; the purity and yield data of the sucralose crude product obtained by 17 times of recycling are shown in table 6:
TABLE 6 sucralose crude product purity and yield
Note: theoretical maximum yield 121.18%.
Example 4
The crude sucralose product is prepared according to the method in example 1, which is different from the method in example 1 in that:
in the step (1), the main components of the used first solution are shown in Table 7, the volume of ethyl acetate for single extraction is 400mL, the extraction temperature is 55 ℃, the extraction time is 20min, the extraction step is repeated for 6 times for the water phase, and the content of sucralose-6-acetate in the first water phase is 0.04g/L;
TABLE 7 first solution Components Table
| Components | Content (c) of |
| Sucralose-6-acetate | 71.2g/L |
| Sucralose diester | 6.3g/L |
| Tetrachlorosucrose-6-acetate | 7.2g/L |
| NH 4 Cl | 115.3g/L |
| Other organic impurities | 52.3g/L |
| Water (W) | 77.5％ |
In the step (2), the mixture is concentrated and dried under the conditions of 65 ℃ and-0.09 MPa, and sucralose-6-acetate aqueous solution (680 mL, the content of ethyl acetate is 0.37 g/L);
in the step (3), the temperature is reduced to 4 ℃, the alkaline hydrolysis temperature is 4 ℃, the alkaline hydrolysis pH =11.7, the alkaline hydrolysis time is 5h, the neutralization time is reduced to pH =7, the thermal filtration temperature is 65 ℃, and the content of a second aqueous phase (740 mL, the content of sucralose-6-acetate is 0.01 g/L);
in the step (4), the single addition of ethyl acetate is 1200mL, the extraction is carried out for 7 times, the volume of the second ethyl acetate phase is 2690mL, the ethyl acetate phase obtained by the 3 rd to 7 th times of ethyl acetate extraction is used as the 1 st to 5 th times of ethyl acetate extraction of the second water phase in the preparation process of the next batch of crude sucralose products, the washing frequency is 5 times, the single washing is 800mL, the water phase obtained by the 2 nd to 5 th times of washing of the second ethyl acetate phase is sequentially washed by the 1 st to 4 th times of water in the preparation process of the second ethyl acetate phase in the next batch of crude sucralose products, the concentrated drying is carried out at the temperature of 70 ℃ and under the pressure of 0.08MPa, the addition of ethyl acetate is 3 times in the concentrated drying process, the single addition of ethyl acetate is 600mL, and the bx is 53%;
in the step (5), the crystallization temperature is 50 ℃, the crystallization time is 28h, the volume of the fifth ethyl ester phase is 390mL, the washing frequency is 6 times, the water consumption for single washing is 200mL, and the content of sucralose in the sixth ethyl ester phase is 0.05g/L;
in the step (6), the ethyl acetate phase obtained by the ethyl acetate extraction of the second water phase from the 1 st to 5 th times in the preparation process of the crude sucralose product of the previous batch is used for the ethyl acetate extraction of the second water phase from the 3 rd to 7 th times, and the ethyl acetate extraction of the second water phase from the 6 th to 7 th times is carried out by using pure ethyl acetate; the 1 st to 4 th water washing of the second diethyl ester phase utilizes the water phase obtained by the 2 nd to 5 th water washing of the second diethyl ester phase in the preparation process of the crude sucralose of the previous batch, and the 5 th water washing of the second diethyl ester phase is carried out by pure water; the purity and yield data of the sucralose crude product obtained by recycling 17 times are shown in table 8:
TABLE 8 sucralose crude product purity and yield
Note: theoretical maximum yield 117.45%.
Example 5
The crude sucralose product is prepared according to the method of example 1, which is different from example 1 in that:
in the step (1), the main components of the used first solution are shown in table 9, the volume of ethyl acetate for single extraction is 500mL, the extraction temperature is 60 ℃, the extraction time is 10min, the extraction step is repeated for 6 times for the aqueous phase, and the content of sucralose-6-acetate in the first aqueous phase is 0.03g/L;
TABLE 9 first solution Components Table
| Components | Content (c) of |
| Sucralose-6-acetate | 80.0g/L |
| Sucralose diester | 7.1g/L |
| Tetrachlorosucrose-6-acetate | 8.5g/L |
| NH 4 Cl | 131.9g/L |
| Other organic impurities | 69.2g/L |
| Water (W) | 73.5％ |
In the step (2), the mixture is concentrated and dried under the conditions of 60 ℃ and-0.09 MPa, and sucralose-6-acetate aqueous solution (700 mL, the content of ethyl acetate is 0.50 g/L);
in the step (3), the temperature is reduced to 0 ℃, the alkaline hydrolysis temperature is 5 ℃, the alkaline hydrolysis pH =13.0, the alkaline hydrolysis time is 3h, and a second water phase (770 mL, the content of sucralose-6-acetate is 0.05 g/L);
in the step (4), the single addition amount of ethyl acetate is 1540mL, the extraction is carried out for 7 times, the volume of the second ethyl ester phase is 3360mL, the ethyl ester phase obtained by the 3-7 times of ethyl acetate extraction is used as the 1-5 times of ethyl acetate extraction of the second water phase in the preparation process of the next batch of crude sucralose products, the washing frequency is 5 times, the water phase obtained by the 2-5 times of washing of the second ethyl ester phase is sequentially washed by the 1-4 times of water of the second ethyl ester phase in the preparation process of the next batch of crude sucralose products, 500mL of water is used for single washing, the ethyl acetate is concentrated and dried under the conditions of 60 ℃ and 0.1MPa, the addition frequency of the ethyl acetate is 3 times in the concentrated and dried process, the single addition amount of the ethyl acetate is 700mL, and the Bx is 60%;
in the step (5), the crystallization temperature is 45 ℃, the crystallization time is 24h, the volume of the fifth ethyl ester phase is 360mL, the washing times are 7 times, the water consumption for single washing is 150mL, and the content of sucralose in the sixth ethyl ester phase is 0.08g/L;
in the step (6), the ethyl acetate phase obtained by the ethyl acetate extraction of the second water phase from the 1 st to the 5 th times in the preparation process of the sucralose crude product of the previous batch is used for the ethyl acetate extraction of the second water phase from the 3 rd to the 7 th times, and the ethyl acetate extraction of the second water phase from the 6 th to the 7 th times is carried out by using pure ethyl acetate; the 1 st to 4 th water washing of the second diethyl ester phase utilizes the water phase obtained by the 2 nd to 5 th water washing of the second diethyl ester phase in the preparation process of the crude sucralose of the previous batch, and the 5 th water washing of the second diethyl ester phase is carried out by pure water; the purity and yield data of the sucralose crude product obtained by recycling 17 times are shown in table 10:
TABLE 10 sucralose crude purity and yield
Note: theoretical maximum yield 117.95%.
Example 6
The crude sucralose product is prepared according to the method of example 1, which is different from example 1 in that:
in the step (1), the main components of the used first solution are shown in table 11, the volume of ethyl acetate for single extraction is 500mL, the extraction temperature is 45 ℃, the extraction time is 20min, the extraction step is repeated for 7 times for the aqueous phase, and the content of sucralose-6-acetate in the first aqueous phase is 0.07g/L;
TABLE 11 first solution ingredients Table
| Components | Content (wt.) |
| Sucralose-6-acetate | 76.1g/L |
| Sucralose diester | 6.7g/L |
| Tetrachlorosucrose-6-acetate | 8.3g/L |
| NH 4 Cl | 131.4g/L |
| Other organic impurities | 60.2g/L |
| Water (I) | 74.8％ |
In the step (2), the mixture is concentrated and dried under the conditions of 80 ℃ and-0.08 MPa, and aqueous solution (690 mL, the content of ethyl acetate is 0.32 g/L) of sucralose-6-acetate is obtained;
in the step (3), the temperature is reduced to 5 ℃, the alkaline hydrolysis temperature is 5 ℃, the alkaline hydrolysis pH =12.8, the alkaline hydrolysis time is 4h, the neutralization temperature is 55 ℃, the hot filtration temperature is 55 ℃, and a second aqueous phase (810 mL, the content of sucralose-6-acetate is 0.02 g/L);
in the step (4), the single addition of ethyl acetate is 2000mL, extraction is carried out for 5 times, the volume of the second ethyl acetate phase is 4300mL, the ethyl acetate phase obtained by the 3 rd to 5 th times of ethyl acetate extraction is used as the 1 st to 3 rd times of ethyl acetate extraction of the second water phase in the preparation process of the next batch of sucralose crude products, the washing frequency is 5 times, 500mL of water is used for single washing, the water phase obtained by the 2 nd to 5 th times of washing of the second ethyl acetate phase is sequentially washed by the 1 st to 4 th times of water in the preparation process of the second ethyl acetate phase in the next batch of sucralose crude products, concentrated drying is carried out under the conditions of 65 ℃ and 0.09MPa, the addition of ethyl acetate is 4 times in the concentrated drying process, the single addition of ethyl acetate is 900mL, and the Bx is 57%;
in the step (5), the crystallization temperature is 50 ℃, the crystallization time is 26h, the volume of the fifth ethyl ester phase is 370mL, the washing frequency is 6 times, the water consumption for single washing is 180mL, and the content of sucralose in the sixth ethyl ester phase is 0.07g/L;
in the step (6), the ethyl acetate extraction of the 1 st to 3 rd times of the second water phase is performed by using the ethyl acetate phase obtained by the ethyl acetate extraction of the 3 rd to 5 th times of the second water phase in the preparation process of the previous batch of crude sucralose product, and the ethyl acetate extraction of the 4 th to 5 th times of the second water phase is performed by using pure ethyl acetate; the 1 st to 4 th water washing of the second diethyl ester phase utilizes the water phase obtained by the 2 nd to 5 th water washing of the second diethyl ester phase in the preparation process of the crude sucralose of the previous batch, and the 5 th water washing of the second diethyl ester phase is carried out by pure water; the purity and yield data of the sucralose crude product obtained by recycling 17 times are shown in table 12:
TABLE 12 sucralose crude product purity and yield
Note: theoretical maximum yield 118.15%.
Example 7
The crude sucralose product is prepared according to the method of example 1, which is different from example 1 in that:
in the step (1), the main components of the used first solution are shown in table 13, the volume of ethyl acetate for single extraction is 200mL, the extraction temperature is 60 ℃, the extraction time is 15min, the extraction step is repeated for 7 times for the aqueous phase, and the content of sucralose-6-acetate in the first aqueous phase is 0.06g/L;
TABLE 13 first solution ingredients Table
| Components | Content (wt.) |
| Sucralose-6-acetate | 61.2g/L |
| Sucralose diester | 4.7g/L |
| Tetrachlorosucrose-6-acetate | 5.5g/L |
| NH 4 Cl | 97.3g/L |
| Other organic impurities | 34.2g/L |
| Water (W) | 81.9％ |
In the step (2), the mixture is concentrated and dried under the conditions of 70 ℃ and-0.08 MPa, and the trichlorosucrose-6-acetate aqueous solution (630 mL, the content of ethyl acetate is 0.22 g/L);
in the step (3), the temperature is reduced to 3 ℃, the alkaline hydrolysis temperature is 3 ℃, the alkaline hydrolysis pH =12.4, the alkaline hydrolysis time is 3.5h, the neutralization temperature is 50 ℃, the hot filtration temperature is 50 ℃, and a second aqueous phase (670 mL, the content of sucralose-6-acetate is 0.05 g/L);
in the step (4), 1400mL of ethyl acetate is added once, 3100mL of the volume of the second diethyl phase, 5 times of washing, 700mL of water is used for washing once, and 1 st to 4 th washing of the second diethyl phase in the preparation process of the next batch of crude sucralose is carried out sequentially by the water phase obtained by the 2 nd to 5 th washing of the second diethyl phase, the ethyl acetate is added 2 times in the concentration and drying process, 800mL of ethyl acetate is added once, and 48% of bx is added;
in the step (5), the crystallization temperature is 40 ℃, the crystallization time is 34h, the volume of the fifth ethyl ester phase is 400mL, the washing frequency is 5 times, the water consumption for single washing is 200mL, and the content of sucralose in the sixth ethyl ester phase is 0.04g/L;
in the step (6), the 1 st to 4 th water washing of the second diethyl ester phase is carried out by using the water phase obtained by the 2 nd to 5 th water washing of the second diethyl ester phase in the preparation process of the previous batch of crude sucralose, and the 5 th water washing of the second diethyl ester phase is carried out by using pure water; the purity and yield data of the sucralose crude product obtained by recycling 17 times are shown in table 14:
TABLE 14 sucralose crude purity and yield
Note: theoretical maximum yield 115.34%.
Example 8
The crude sucralose product is prepared according to the method of example 1, which is different from example 1 in that:
in the step (1), the main components of the used first solution are shown in table 15, the volume of ethyl acetate for single extraction is 300mL, the extraction temperature is 40 ℃, the extraction time is 20min, the extraction step is repeated for 5 times for the aqueous phase, and the content of sucralose-6-acetate in the first aqueous phase is 0.09g/L;
TABLE 15 first solution Components Table
| Components | Content (wt.) |
| Sucralose-6-acetate | 57.7g/L |
| Sucralose diester | 5.1g/L |
| Tetrachlorosucrose-6-acetate | 6.4g/L |
| NH 4 Cl | 89.9g/L |
| Other organic impurities | 33.1g/L |
| Water (W) | 82.8％ |
In the step (2), the mixture is concentrated and dried under the conditions of 70 ℃ and-0.09 MPa, and the trichlorosucrose-6-acetic ester aqueous solution (600 mL, the content of ethyl acetate is 0.48 g/L);
in the step (3), the temperature is reduced to 1 ℃, the alkaline hydrolysis temperature is 1 ℃, the alkaline hydrolysis pH is =12.0, the alkaline hydrolysis time is 4.5h, the neutralization temperature is 45 ℃, the hot filtration temperature is 640mL, and the content of sucralose-6-acetate is 0.04g/L;
in the step (4), the single addition of ethyl acetate is 1000mL, the extraction is carried out for 7 times, the volume of the diethyl phase is 2200mL, the ethyl acetate phase obtained by the 3 rd to 7 th times of ethyl acetate extraction is used as the ethyl acetate extraction of the 1 st to 5 th times of the second water phase in the preparation process of the next batch of crude sucralose, the washing frequency is 5 times, 300mL of water is used for the single washing, the water phase obtained by the 2 nd to 5 th times of the second ethyl acetate phase is sequentially washed by the 1 st to 4 th times of the second ethyl acetate phase in the preparation process of the next batch of crude sucralose, the concentrated drying is carried out under the conditions of 80 ℃ and 0.08MPa, the addition of ethyl acetate is 2 times in the concentrated drying process, the single addition of ethyl acetate is 800mL, and the bx is 45%;
in the step (5), the crystallization temperature is 40 ℃, the crystallization time is 32h, the volume of the fifth ethyl ester phase is 410mL, the washing times are 5 times, the water consumption for single washing is 220mL, and the content of sucralose in the sixth ethyl ester phase is 0.02g/L;
in the step (6), the ethyl acetate phase obtained by the ethyl acetate extraction of the second water phase from the 1 st to the 5 th times in the preparation process of the sucralose crude product of the previous batch is used for the ethyl acetate extraction of the second water phase from the 3 rd to the 7 th times, and the ethyl acetate extraction of the second water phase from the 6 th to the 7 th times is carried out by using pure ethyl acetate; the 1 st to 4 th water washing of the second diethyl ester phase utilizes the water phase obtained by the 2 nd to 5 th water washing of the second diethyl ester phase in the preparation process of the crude sucralose of the previous batch, and the 5 th water washing of the second diethyl ester phase is carried out by pure water; the purity and yield data of the sucralose crude product obtained by recycling 17 times are shown in table 16:
TABLE 16 sucralose crude purity and yield
Note: theoretical maximum yield 118.35%.
In the process of applying, the sucralose and the impurities are in an equilibrium state in the ethyl ester phase, that is, the sucralose yield is more than 105% by controlling 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 water phase and the third water phase reaches the specified standard; (3) During crystallization, the water content in the ethyl acetate phase reaches the specified standard; (4) Residual sugar in the sixth ethyl ester phase needs to reach a set standard; and (5) the crystallization conditions are stable. The system is characterized in that: due to the conversion of sucralose diester and tetrachlorosucrose-6-acetate, sucralose can achieve a yield of greater than 110% (based on the conversion of sucralose-6-acetate to sucralose); the mutual washing and the application of the ester phase and the water phase can avoid the loss of the sucralose caused by the residue in the sugar residue and the waste water to the maximum extent. Moreover, the residual sucralose in the fourth water phase and the fifth water phase is fully utilized, and the yield of the sucralose is improved.
From the above examples, it can be seen that in the initial few operation schemes, for example, in the recycling process of 1 st to 2 nd, the yield is low because the ethyl acetate and water recycled in the system contain lower components convertible to sucralose. After the sucralose-6-acetate is recycled for 3 times, if the sucralose-6-acetate is completely converted into sucralose as a yield calculation mode, the yield exceeds 100%, because the first aqueous solution also comprises other components (sucralose diester and tetrachlorosucrose-6-acetate) capable of being converted into sucralose, the method provided by the invention can convert the sucralose diester and tetrachlorosucrose-6-acetate into sucralose, so that the yield of the sucralose is obviously improved, compared with a method for preparing sucralose by using high-purity sucralose-6-acetate as a raw material and carrying out alkaline hydrolysis, the method provided by the invention has the advantages that the yield of sucralose is obviously improved, the first aqueous solution is used as a raw material, the sucralose-6-acetate crude product does not need to be purified, the process is simpler, the loss of sucralose-6-acetate caused by purification before the sucralose-6-acetate is subjected to alkaline hydrolysis in the traditional process is avoided, and the method provided by the invention has very obvious advantages.
The water phases (the fourth water phase and the fifth water phase) in the specific steps in the production flow are stored and are continuously used for removing the ethyl acetate in the alkaline hydrolysis reaction system in the next production flow, so that the generation of byproducts acetic acid and ethanol can be reduced, and the purity of the sucralose is improved; meanwhile, sucralose does not flow out of the production flow through internal circulation of the sucralose in the production flow, so that sucralose contained in the fourth water phase and the fifth water phase can be fully utilized, the loss of the sucralose is greatly reduced, and the overall yield of the sucralose is greatly improved. Compared with the existing crystallization process, the crystallization process has the advantages that the yield of the process of the sucralose is not high (the ratio of the crystallization product to the crystallization raw material), but the purity of the crude sucralose is high; although the yield of the crystallization process is not high, the fourth aqueous phase and the fifth aqueous phase of the previous process are introduced into the production process due to the recycling of the fourth aqueous phase and the fifth aqueous phase (the non-crystallized sucralose in the current process enters the next production process), so that the ratio of the yield of the crude sucralose product to the theoretical yield (the theoretical yield calculated by the input raw materials) is obviously higher than that of the existing production process from the viewpoint of the whole production process. By adopting the method provided by the invention, the purity of the sucralose crude product is improved, the difficulty of subsequent treatment is reduced, and the overall yield of the sucralose raw material is improved. In the method provided by the invention, the alkaline hydrolysis step uses the alkali metal strong oxide to replace the traditional sodium methoxide/methanol reaction system with higher hazard, and the method is safe and environment-friendly. In the recycling process of the fourth water phase and the fifth water phase, fat-soluble caramel impurities in the system are introduced into the ethyl acetate, so that the difficulty in impurity removal and the difficulty in waste treatment are reduced, and the solubility of the sucralose in the ethyl acetate is increased, so that the sucralose is fully enriched and crystallized in the crystallization process, and the yield is improved.
In conclusion, the method provided by the invention adopts alkali metal hydroxide and a water system to carry out alkaline hydrolysis, the ethyl acetate/water double-system is used for extraction and impurity removal (the fourth water phase and the fifth water phase are used for dissolving the first ethyl ester phase concentrate), the sucralose-6-acetate, the sucralose diester and the tetrachlorosucrose-6-acetate can be converted into the sucralose, and the sucralose is fully enriched and crystallized in the ethyl ester phase, so that the loss caused by purification before the alkaline hydrolysis of the sucralose-6-acetate in the traditional process and the loss of some useful impurities are avoided, the yield of the sucralose is obviously improved, a higher value is created, and the method has a great industrial prospect.
The above description of the embodiments is only intended to facilitate the understanding of the method of the invention and its core idea. It should be noted that, for those skilled in the art, it is possible to make various improvements and modifications to the present invention without departing from the principle of the present invention, and those improvements and modifications also fall within the scope of the claims of the present invention. Various modifications to these embodiments will be readily apparent to those skilled in the art, and the generic principles defined herein may be applied to other embodiments without departing from the spirit or scope of the invention. Thus, the present invention is not intended to be limited to the embodiments shown herein but is to be accorded the widest scope consistent with the principles and novel features disclosed herein.
Claims (14)
1. A method for preparing sucralose crude product by using a hydrolysis system is characterized by comprising the following steps:
(1) Extracting the raw material liquid with ethyl acetate to obtain a first ethyl ester phase and a first water phase respectively; concentrating the first ethyl ester phase to obtain a first ethyl ester phase concentrate; the raw material liquid is an aqueous solution containing sucralose-6-acetate, sucralose diester and tetrachlorosucrose-6-acetate;
(2) Mixing and dissolving the first ethyl ester phase concentrate and water, and concentrating to obtain a sucralose-6-acetate aqueous solution;
(3) Mixing the sucralose-6-acetate aqueous solution with an alkali metal hydroxide for an alkaline hydrolysis reaction, neutralizing the obtained reaction solution, and then carrying out hot filtration to obtain a second water phase;
(4) Carrying out ethyl acetate extraction on the second water phase to respectively obtain a second ethyl ester phase and a third water phase;
(5) Washing the second ethyl ester phase with water to respectively obtain a fourth water phase and a third ethyl ester phase; the fourth aqueous phase is reused in step (2) for dissolving the first ethyl ester phase concentrate;
(6) Mixing the third ethyl ester phase with ethyl acetate, and carrying out azeotropic dehydration to obtain a third ethyl ester phase concentrate; mixing the third ester phase concentrate with ethyl acetate to obtain a fourth ester phase;
(7) Crystallizing the fourth ethyl ester phase to respectively obtain a sucralose crude product and a fifth ethyl ester phase;
(8) Washing the fifth ethyl ester phase with water to obtain a fifth water phase and a sixth ethyl ester phase respectively; the fifth aqueous phase is recycled to step (2) for dissolving the first ethyl ester phase concentrate.
2. The method according to claim 1, wherein in the step (1), the temperature of the ethyl acetate extraction is 40-60 ℃, and the extraction times are 5-8; the volume ratio of the raw material liquid to ethyl acetate for single ethyl acetate extraction is 1:0.2 to 0.4.
3. The process according to claim 1 or 2, wherein in step (1) the sucralose-6-acetate content in the first aqueous phase is <0.1g/L.
4. The method according to claim 1, wherein in step (2), the content of ethyl acetate in the sucralose-6-acetate aqueous solution is less than 0.5g/L.
5. The method according to claim 1, wherein in the step (3), the pH value of the alkaline hydrolysis reaction is 11-13, the temperature is 0-10 ℃, and the time is 3-6 h.
6. The method according to claim 1, wherein the temperature of the hot filtration in the step (3) is 45 to 70 ℃.
7. The method according to claim 1, wherein in the step (4), the number of the ethyl acetate extractions is 4 to 7; the volume ratio of the second aqueous phase to ethyl acetate for single-time extraction is 1:1 to 3;
combining ethyl ester phases obtained by the 1 st to 2 nd times of ethyl acetate extraction to be used as a second ethyl ester phase;
and (4) using the ethyl acetate phase obtained by extracting the ethyl acetate for 3-7 times for extracting the ethyl acetate of the second water phase in the preparation process of the sucralose crude product of the next batch.
8. The process according to claim 1 or 7, wherein in step (4) the sucralose content in the third aqueous phase is <0.5g/L.
9. The method according to claim 1, wherein in the step (5), the number of times of the water washing is 3 to 5; the volume ratio of the second diethyl phase to the single-use water for water washing is 1:0.1 to 0.3;
taking the water phase obtained by the 1 st water washing as a fourth water phase;
and (3) using the water phase obtained by the 2 nd-5 th water washing for the water washing of the second ethyl ester phase in the next sucralose crude product preparation process.
10. The process according to claim 1 or 9, wherein in step (5) the sucralose content in the third aqueous phase is <0.5g/L.
11. The method of claim 1, wherein in step (6), the water content of the third ethyl ester phase concentrate is <0.5 wt.%.
12. The method according to claim 1 or 11, wherein in step (6), the fourth ethyl ester phase has a sugar degree of 40 to 60%.
13. The method according to claim 1, wherein in the step (7), the temperature of the crystallization is 40-60 ℃ and the time is 12-35 h.
14. The method of claim 1, wherein the sucralose content in the sixth ethyl ester phase is <0.1g/L.
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| CN116075518A (en) * | 2022-10-19 | 2023-05-05 | 安徽金禾实业股份有限公司 | Method for preparing crude sucralose by utilizing alcohol-water alkaline hydrolysis system |
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| US5530106A (en) * | 1993-03-12 | 1996-06-25 | Mcneil-Ppc, Inc. | Recovery of sucralose intermediates |
| US5498709A (en) * | 1994-10-17 | 1996-03-12 | Mcneil-Ppc, Inc. | Production of sucralose without intermediate isolation of crystalline sucralose-6-ester |
| US7049435B2 (en) * | 2002-03-08 | 2006-05-23 | Tate & Lyle Public Limited Company | Extractive methods for purifying sucralose |
| CN106674293B (en) * | 2016-12-09 | 2019-05-03 | 福建科宏生物工程股份有限公司 | A method of sucralose-6-acetic ester waste mother liquor is handled using hydrolysis method |
| CN109467578B (en) * | 2018-03-14 | 2022-01-21 | 刘静 | Method for extracting sucralose from multiple mother liquor |
| CN110563780B (en) * | 2019-08-30 | 2020-08-14 | 山东新和成精化科技有限公司 | Post-treatment method of sucralose chlorination liquid and application of sucralose chlorination liquid in preparation of sucralose |
| WO2023279278A1 (en) * | 2021-07-07 | 2023-01-12 | 安徽金禾实业股份有限公司 | Method for purifying sucralose-6-ester |
| WO2023279276A1 (en) * | 2021-07-07 | 2023-01-12 | 安徽金禾实业股份有限公司 | Method for purifying sucralose-6-ester |
| CN113717237B (en) * | 2021-08-17 | 2024-03-29 | 安徽金禾实业股份有限公司 | Method for preparing sucralose from sucralose-6-acetate neutralization solution |
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| CN116075518B (en) * | 2022-10-19 | 2023-12-08 | 安徽金禾实业股份有限公司 | Method for preparing crude sucralose by utilizing alcohol-water alkaline hydrolysis system |
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