A process for the preparation of a trichlorosucrose fine

Abstract

The application provides a preparation method of trichlorosucrose fine product, and relates to the technical field of fine chemical industry.The trichlorosucrose fine product is prepared by the following steps: ethyl acetate beating treatment of trichlorosucrose crude product, twice activated carbon decolorization and impurity removal in different stages, and thrice crystallization, so that the impurities in the trichlorosucrose crude product and the impurities generated due to oxidation in the process of recycling of the crystallization mother liquor can be removed, the problem of impurity enrichment of the crystallization mother liquor in the recycling process is solved, the crystallization mother liquor generated in the refining process can be recycled repeatedly, the loss of the trichlorosucrose in the purification process is reduced, and the yield of the trichlorosucrose is significantly improved.Further, the preparation method of the trichlorosucrose fine product can be effectively combined with the method of the trichlorosucrose crude product, the crystallization mother liquor formed in the preparation process of the trichlorosucrose fine product can be recycled and applied, the yield of the trichlorosucrose is significantly increased, the production cost is significantly reduced, and the method has a high industrialization prospect.

Description

TECHNICAL FIELD

[0001] The present application relates to the field of fine chemical technology, in particular to a preparation method of sucralose fine product. BACKGROUND

[0002] Sucralose, commonly known as sucrose, is a white crystalline powder or granular, which is a new generation of sweetener with sucrose as raw material. Its sweetness is 600 times that of sucrose, and it has pure taste and does not participate in human metabolism, which can be used by diabetics, patients with cardiovascular and cerebrovascular diseases and the elderly. It has the characteristics of good stability and high safety, and is widely used in food, beverage, daily chemical and pharmaceutical fields.

[0003] At present, the production process of sucralose mainly uses sucrose as raw material to obtain sucrose-6-acetate by esterification, sucrose-6-acetate to obtain sucralose-6-acetate by chlorination, and sucralose-6-acetate to obtain sucralose fine product by alcoholysis and purification. Among them, the synthesis of sucrose-6-acetate mainly includes original acetic anhydride process (such as Chinese patents CN106749440A and CN105254684A) and organic tin process (such as Chinese patents CN102639550A and CN1528772A). The synthesis of sucralose-6-acetate mainly includes phosgene / solid phosgene process (CN103328495A and CN1660868A) and chlorosulfoxide process (such as Chinese patents CN101270136A and CN102417526A). There are many methods for preparing sucralose from sucralose-6-acetate, such as sodium methoxide method (such as Chinese patents CN101918421A and CN1176094A), organic amine method (such as Chinese patents CN101260127A, CN112771060A and CN101260127A), basic ion exchange resin method (such as Chinese patents CN112409419A and CN102336787A), alkali metal oxide method (such as Chinese patents CN113004345A, CN104004032A and CN112805291A), and alkali metal hydroxide method (such as Chinese patents CN1814609A, CN101012250A and CN102321122A).

[0004] The traditional production method of sucralose fine product mainly comprises: taking sucralose-6-acetate pure product (the purity is above 99%) as raw material, preparing sucralose crude product through alcoholysis (sodium methoxide / methanol) or alkaline hydrolysis (liquid alkali / water), and then obtaining sucralose fine product through purification (butyl acetate extraction to remove impurities, and then crystallization in water). In the purification process, the crystallization mother liquor is recycled, and needs to be concentrated in the recycling process. However, the above purification step will cause the oxidation of sucralose, forming new impurities, which will be enriched in the recycling process of the crystallization mother liquor, and then affect the crystallization of sucralose. At this time, the crystallization mother liquor (about 5 times) cannot be recycled and can only be treated as waste water. SUMMARY

[0005] Therefore, the purpose of the present application is to provide a preparation method of sucralose fine product. The method provided by the present application can recycle the crystallization mother liquor for multiple times, and has high yield and high purity of sucralose fine product.

[0006] In order to achieve the above-mentioned purpose of the application, the present application provides the following technical scheme:

[0007] The present application provides a preparation method of sucralose fine product, comprising the following steps:

[0008] The present application provides a preparation method of sucralose fine product, comprising the following steps:

[0009] (1) Beating and decolorizing: mixing sucralose crude product and ethyl acetate, carrying out beating, and then carrying out solid-liquid separation to obtain beating mother liquor and beating target product; dissolving the beating target product in water, carrying out activated carbon decolorization on the obtained beating target product aqueous solution to obtain beating and decolorizing target product liquid;

[0010] (2) First crystallization: concentrating the beating and decolorizing target product liquid, and carrying out first crystallization on the obtained beating and decolorizing target product concentrate to obtain first crystallization target product and primary crystallization mother liquor;

[0011] (3) Second crystallization: dissolving the first crystallization target product in water, and carrying out second crystallization on the obtained first crystallization target product aqueous solution to obtain second crystallization target product and secondary crystallization mother liquor; the secondary crystallization mother liquor is used for dissolving the beating target product in step (1);

[0012] (4) third crystallization: dissolving the second crystallization target product in water, and then performing solid-liquid separation on the obtained second crystallization target product aqueous solution after active carbon decolorization to obtain a second crystallization decolorization target product aqueous solution and recovered active carbon respectively; concentrating the second crystallization decolorization target product aqueous solution, and then performing third crystallization on the obtained second crystallization decolorization target product concentrate to obtain third crystallization target product and third crystallization mother liquor respectively; drying the third crystallization target product to obtain sucralose fine product; and the third crystallization mother liquor is used in step (3) to dissolve the first crystallization target product, and the recovered active carbon is used in step (1) to perform active carbon decolorization on the beating target product aqueous solution.

[0013] Preferably, in step (1), the sucralose crude product comprises the following mass percentage of components: sucralose 85-95%, sucralose-6-acetate 0.5-1%, ethyl acetate 1-3%, and caramel-like impurities 1-13.5%.

[0014] Preferably, in step (1), the ratio of the mass of the sucralose crude product to the volume of ethyl acetate for beating is 1 kg: 1-1.5 L.

[0015] Preferably, in step (1), the temperature of the dissolving is 30-50°C.

[0016] The sugar content of the beating target product aqueous solution is 20-40%.

[0017] Preferably, in step (2), the sugar content of the beating decolorization target product concentrate is 40-65%.

[0018] Preferably, in step (2), the temperature of the first crystallization is room temperature, and the time is 8-16 h.

[0019] Preferably, in step (3), the temperature of the dissolving is 40-60°C.

[0020] The sugar content of the first crystallization target product aqueous solution is 40-65%.

[0021] Preferably, in step (3), the temperature of the second crystallization is room temperature, and the time is 8-16 h.

[0022] Preferably, in step (4), the temperature of the dissolving is 40-60°C.

[0023] The sugar content of the second crystallization decolorization target product aqueous solution is 20-30%.

[0024] Preferably, in step (4), the sugar content of the second crystallization decolorization target product concentrate is 40-65%.

[0025] Preferably, in step (4), the temperature of the third crystallization is 30-50°C, and the time is 4-12 h.

[0026] Preferably, the method for preparing the crude sucralose comprises the following steps:

[0027] (a) ethyl acetate extraction of a raw material solution to obtain a first ethyl acetate phase and a first water phase, respectively; concentration of the first ethyl acetate phase to obtain a first ethyl acetate phase concentrate; the raw material solution is an aqueous solution comprising sucralose-6-acetate, sucralose diester and tetra- chlorosucrose-6-acetate;

[0028] (b) mixing and dissolving the first ethyl acetate phase concentrate with water, and concentrating to obtain a sucralose-6-acetate aqueous solution;

[0029] (c) mixing the sucralose-6-acetate aqueous solution with an alkali metal hydroxide to perform an alkaline hydrolysis reaction, and filtering the obtained reaction solution after neutralization to obtain a second water phase;

[0030] (d) ethyl acetate extraction of the second water phase to obtain a second ethyl acetate phase and a third water phase, respectively;

[0031] (e) water washing of the second ethyl acetate phase to obtain a fourth water phase and a third ethyl acetate phase, respectively; the fourth water phase is used for dissolving the first ethyl acetate phase concentrate in step (b);

[0032] (f) mixing the third ethyl acetate phase with ethyl acetate to perform azeotropic water removal to obtain a third ethyl acetate phase concentrate; mixing the third ethyl acetate phase concentrate with ethyl acetate to obtain a fourth ethyl acetate phase;

[0033] (g) crystallization of the fourth ethyl acetate phase to obtain a crude sucralose and a fifth ethyl acetate phase, respectively;

[0034] (h) water washing of the fifth ethyl acetate phase to obtain a fifth water phase and a sixth ethyl acetate phase, respectively; the fifth water phase is used for dissolving the first ethyl acetate phase concentrate in step (b).

[0035] Preferably, the beating mother liquor and the primary crystallization mother liquor are used for preparing the crude sucralose.

[0036] Preferably, when reused, the beating mother liquor is used for dissolving the first ethyl acetate phase concentrate, and the primary crystallization mother liquor is mixed with the third ethyl acetate phase to perform azeotropic water removal.

[0037] Preferably, the sucralose content in the third water phase, the fourth water phase and the fifth water phase is independently <0.5 g / L.

[0038] Preferably, in step (a), the temperature of the ethyl acetate extraction is 40-60℃, and the extraction is performed 5-8 times; the volume ratio of the raw material solution to the ethyl acetate used for a single ethyl acetate extraction is 1:0.2-0.5.

[0039] Preferably, in step (b), the content of ethyl acetate in the aqueous solution of sucralose-6-acetate is <0.5 g / L.

[0040] Preferably, in step (c), the pH value of the alkaline hydrolysis reaction is 11-13, the temperature is 0-10℃, and the time is 3-6 h.

[0041] Preferably, in step (c), the temperature of the neutralization and filtration is independently 50-70℃.

[0042] Preferably, in step (d), the ethyl acetate extraction is performed 4-7 times; the volume ratio of the second aqueous phase to the ethyl acetate used for a single ethyl acetate extraction is 1:1-3.

[0043] The ethyl acetate phases obtained by the first 1-2 ethyl acetate extractions are combined as a second ethyl acetate phase;

[0044] The ethyl acetate phases obtained by the third 3-7 ethyl acetate extractions are used for the ethyl acetate extraction of the second aqueous phase in the preparation of the next batch of sucralose crude product.

[0045] Preferably, in step (e), the water washing is performed 3-6 times; the volume ratio of the second ethyl acetate phase to the water used for a single water washing is 1:0.1-0.3.

[0046] The aqueous phase obtained by the first water washing is used as a fourth aqueous phase;

[0047] The aqueous phases obtained by the second 2-6 water washings are used for the water washing of the second ethyl acetate phase in the preparation of the next batch of sucralose crude product.

[0048] Preferably, in step (f), the water content of the third ethyl acetate phase concentrate is <0.5 wt%.

[0049] Preferably, in step (f), the sugar content of the fourth ethyl acetate phase is 40-60%.

[0050] Preferably, in step (g), the temperature of the crystallization is 40-60℃, and the time is 12-30 h.

[0051] The prior art cannot achieve the material balance between the target product and impurities in the process from the crude sucralose to the fine sucralose, and eventually the mother liquor has to be abandoned after several cycles due to too many impurities. The preparation method provided by the present application can effectively remove the impurities in the crude sucralose and the impurities generated by oxidation during the recycling process of the crystallization mother liquor through ethyl acetate beating treatment of the crude sucralose, twice decolorization and impurity removal by activated carbon at different stages, and three times of crystallization, ensuring the stability of the subsequent crystallization mother liquor and solving the problem of impurity enrichment in the recycling process of the crystallization mother liquor, so that the crystallization mother liquor produced in the refining process can be repeatedly recycled, reducing the loss of sucralose in the purification process and significantly improving the yield of sucralose. By recycling the secondary crystallization mother liquor to dissolve the beating target product and the tertiary crystallization mother liquor to dissolve the first crystallization target product, the residual sucralose in the secondary and tertiary crystallization mother liquors can be fully utilized, reducing the large loss of sucralose during crystallization and significantly improving the yield of sucralose.

[0052] Further, the beating mother liquor contains a large amount of fat-soluble impurities and part of the sucralose, and the primary crystallization mother liquor contains residual sucralose. By using the beating mother liquor and the primary crystallization mother liquor to prepare the crude sucralose, the present application can avoid the loss of sucralose and improve the overall yield of sucralose. The preparation method provided by the present application can effectively realize the combination of the preparation of crude sucralose and the purification of crude sucralose, achieve the balance of sucralose and impurities in the purification process, and realize the long-term and multiple recycling of the mother liquor.

[0053] Further, the present application performs alkaline hydrolysis in an alkali metal hydroxide-water system. Sucralose-6-acetate, sucralose diester and sucralose-6-acetate will be hydrolyzed in the presence of strong alkali solution to generate corresponding sucralose and sucralose, and sucralose can continue to be dechlorinated to form sucralose in the presence of strong alkali solution. The sucralose-6-acetate and impurities (sucralose diester and sucralose-6-acetate) in the raw material liquid are all converted to sucralose, thereby significantly improving the raw material conversion rate and the yield of sucralose. Compared with the method of preparing sucralose by hydrolyzing high-purity sucralose-6-acetate, the raw material conversion rate and the yield of sucralose are significantly improved in the method provided by the present application. The present application adopts a double system of ethyl acetate-water, which can realize mutual recycling extraction and impurity removal between the two systems to enrich sucralose, so that sucralose can be crystallized in large quantities in ethyl acetate, and sucralose can be recycled through repeated recycling, avoiding the loss of sucralose and greatly improving the overall yield of sucralose. Moreover, compared with the traditional sodium methoxide / methanol system hydrolysis, the production cost of the preparation method provided by the present application is low, safe and environmentally friendly. BRIEF DESCRIPTION OF DRAWINGS

[0054] Figure 1 A process flow chart for preparing sucralose fine product;

[0055] Figure 2 A process flow chart for preparing sucralose fine product using hydrolysis system. DETAILED DESCRIPTION

[0056] The present application is further illustrated by the following examples and drawings.

[0057] The present application provides a method for preparing sucralose fine product, comprising the following steps:

[0058] (1) mixing sucralose crude product with ethyl acetate, carrying out beating and solid-liquid separation to obtain beating mother liquor and beating target product respectively; dissolving the beating target product in water, and carrying out activated carbon decolorization on the obtained beating target product aqueous solution to obtain beating decolorization target product liquid;

[0059] (2) concentrating the beating decolorization target product liquid, and carrying out first crystallization on the obtained beating decolorization target product concentrate to obtain first crystallization target product and primary crystallization mother liquor respectively;

[0060] (3) dissolving the first crystallization target product in water, carrying out second crystallization on the obtained first crystallization target product aqueous solution to obtain second crystallization target product and secondary crystallization mother liquor respectively; the secondary crystallization mother liquor is recycled to be used for dissolving the beating target product in step (1);

[0061] (4) dissolving the second crystallization target product in water, carrying out activated carbon decolorization on the obtained second crystallization target product aqueous solution, and then carrying out solid-liquid separation to obtain second crystallization decolorization target product aqueous solution and recovered activated carbon respectively; concentrating the second crystallization decolorization target product aqueous solution, carrying out third crystallization on the obtained second crystallization decolorization target product concentrate to obtain third crystallization target product and tertiary crystallization mother liquor respectively; drying the third crystallization target product to obtain sucralose fine product; the tertiary crystallization mother liquor is recycled to be used for dissolving the first crystallization target product in step (3), and the recovered activated carbon is recycled to be used for activated carbon decolorization on the beating target product aqueous solution in step (1).

[0062] In the present application, all raw material components are commercially available goods well known to those skilled in the art, unless otherwise specified.

[0063] The present application mixes the crude sucralose with ethyl acetate, carries out beating, and then carries out solid-liquid separation to obtain beating mother liquor and beating target product; the beating target product is dissolved in water, the obtained beating target product aqueous solution is mixed with activated carbon to carry out decolorization to obtain beating decolorization target product liquid; the beating mother liquor is used to prepare crude sucralose.

[0064] In the present application, the crude sucralose comprises the following components with mass percentage: sucralose preferably 85-95%, more preferably 88-92%; sucralose-6-acetate preferably 0.5-1%, more preferably 0.6-0.9%; ethyl acetate preferably 1-3%, more preferably 1.5-2.5%; caramel-like impurities preferably 1-13.5%, more preferably 5-10%. In the present application, the mass of the crude sucralose to the volume of ethyl acetate for beating is preferably 1 kg: 1-1.5 L, more preferably 1 kg: 1.1-1.4 L, further preferably 1 kg: 1.3-1.4 L.

[0065] In the present application, the temperature for beating is preferably 20-40℃, more preferably room temperature. The time for beating is preferably 5-15 min, more preferably 10 min; the beating is preferably carried out under stirring. The present application is not particularly limited to the mode for solid-liquid separation, and any mode for solid-liquid separation known to those skilled in the art can be used, such as filtration, suction filtration or pressure filtration. In the present application, the temperature for dissolving is preferably 30-50℃, more preferably 30-45℃, further preferably 30-40℃; the sugar degree (Bx) of the beating target product aqueous solution is preferably 20-40%, more preferably 25-35%, further preferably 30%.

[0066] In the present application, the activated carbon is preferably plant activated carbon, more preferably at least one of coconut shell activated carbon and nutshell activated carbon; coal-based activated carbon will leave sulfur impurities, which will affect the product taste of sucralose, while the plant activated carbon used in the present application has low sulfur content, which will not affect the product quality of sucralose. In the present application, the mass of the activated carbon is preferably 0.5-1% of the dry weight of the crude sucralose, more preferably 0.6-0.9%. In the present application, the temperature for decolorization is preferably 40-50℃, more preferably 45℃, and the time for decolorization is preferably 5-10 min, more preferably 6-8 min; the purpose of the activated carbon decolorization is to remove colored impurities in the crude sucralose. After the activated carbon decolorization is completed, the present application preferably further comprises carrying out solid-liquid separation on the obtained decolorization system to obtain beating decolorization target product liquid and activated carbon residue, respectively. The present application is not particularly limited to the mode for solid-liquid separation, and any mode for solid-liquid separation known to those skilled in the art can be used, such as filtration, suction filtration or pressure filtration. In the present application, the activated carbon residue is preferably subjected to solid waste treatment.

[0067] In the present application, the preparation method of the crude sucralose preferably comprises the following steps:

[0068] (a) ethyl acetate extraction of a raw material solution to obtain a first ethyl acetate phase and a first water phase, respectively; concentration of the first ethyl acetate phase to obtain a first ethyl acetate phase concentrate; the raw material solution is an aqueous solution comprising sucralose-6-acetate, sucralose diester and sucralose-6-acetate;

[0069] (b) mixing and dissolving the first ethyl acetate phase concentrate with water, concentrating to obtain a sucralose-6-acetate aqueous solution;

[0070] (c) mixing the sucralose-6-acetate aqueous solution with an alkali metal hydroxide to perform an alkaline hydrolysis reaction, filtering after neutralization of the obtained reaction solution to obtain a second water phase;

[0071] (d) ethyl acetate extraction of the second water phase to obtain a second ethyl acetate phase and a third water phase, respectively;

[0072] (e) water washing of the second ethyl acetate phase to obtain a fourth water phase and a third ethyl acetate phase, respectively; the fourth water phase is used in step (b) to dissolve the first ethyl acetate phase concentrate;

[0073] (f) mixing the third ethyl acetate phase with ethyl acetate to perform azeotropic water removal to obtain a third ethyl acetate phase concentrate; mixing the third ethyl acetate phase concentrate with ethyl acetate to obtain a fourth ethyl acetate phase;

[0074] (g) crystallization of the fourth ethyl acetate phase to obtain a crude sucralose and a fifth ethyl acetate phase, respectively;

[0075] (h) water washing of the fifth ethyl acetate phase to obtain a fifth water phase and a sixth ethyl acetate phase, respectively; the fifth water phase is used in step (b) to dissolve the first ethyl acetate phase concentrate.

[0076] The raw material liquid is extracted by ethyl acetate to obtain a first ethyl acetate phase and a first water phase; the first ethyl acetate phase is concentrated to obtain a first ethyl acetate phase concentrate; the raw material liquid is an aqueous solution containing sucralose-6-acetate, sucralose diester and tetra-chloro-sucrose-6-acetate. The preparation method of the raw material liquid is not particularly limited in the present application, and the preparation method of sucrose-6-acetate crude product prepared from sucrose as the initial raw material known to those skilled in the art can be used, specifically: sucrose is used as the raw material, N,N-dimethylformamide (DMF) is used as the solvent, organic tin is used as the catalyst, and acetic anhydride is used as the acylating agent to prepare a solution containing sucrose-6-acetate; then the obtained solution containing sucrose-6-acetate is sequentially subjected to chlorination (thionyl chloride), ammonia water neutralization, vacuum concentration to dryness and water dissolution to obtain the raw material liquid. In the present application, the content of sucralose-6-acetate in the raw material liquid is preferably 50-80 g / L, more preferably 55-75 g / L; the mass ratio of sucralose-6-acetate, sucralose diester and tetra-chloro-sucrose-6-acetate in the raw material liquid is preferably 1:0.06-0.15:0.06-0.15; the raw material liquid preferably further comprises NH4Cl and organic impurities, the concentration of NH4Cl is preferably 80-150 g / L, more preferably 80-100 g / L; the concentration of the organic impurities is preferably 30-80 g / L, more preferably 30-50 g / L. In the present application, the temperature of the ethyl acetate extraction is preferably 40-60°C, more preferably 45-55°C, further preferably 50°C; the number of times of the ethyl acetate extraction is not particularly limited in the present application, and the content of sucralose-6-acetate in the water phase (i.e. the first water phase) obtained by the last ethyl acetate extraction is <0.1 g / L, specifically 5-8 times; the time of single ethyl acetate extraction is preferably 10-30 min, more preferably 15-20 min; the volume ratio of the raw material liquid to ethyl acetate for single ethyl acetate extraction is preferably 1:0.2-0.5, more preferably 1:0.3-0.4. In the present application, the ethyl acetate phases obtained by ethyl acetate extraction are combined as the first ethyl acetate phase, the raffinate phase obtained by the last ethyl acetate extraction is the first water phase, and the first water phase is preferably subjected to high-salinity wastewater treatment. The raw material liquid is extracted by hot ethyl acetate (40-60°C) in the present application, which can reduce the use amount of ethyl acetate, increase the dissolution amount of fat-soluble impurities, facilitate the increase of the solubility of subsequent sucralose in ethyl acetate, and further improve the crystallization sugar degree and sucralose crystallization yield.The present application does not have special limitation to the concentrating method, and any concentrating method known to those skilled in the art can be used, such as vacuum concentration. The concentration temperature is preferably 60-80°C, more preferably 65-75°C. The vacuum degree of the concentration is preferably -0.1 to -0.08 MPa (gauge pressure), more preferably -0.09 to -0.08 MPa (gauge pressure). The present application does not have special limitation to the concentration time, and the concentration can be stopped when the ethyl acetate content in the obtained first ethyl ester phase concentrate is less than 0.5 g / L. By controlling the residual amount of ethyl acetate in the first ethyl ester phase concentrate, the present application can avoid the generation of by-products such as acetic acid and ethanol from ethyl acetate in the subsequent alkaline hydrolysis step, and further improve the purity and yield of sucralose.

[0077] After obtaining the first ethyl ester phase concentrate, the present application dissolves the first ethyl ester phase concentrate in water and concentrates to obtain a sucralose-6-acetate aqueous solution. In the present application, the volume ratio of the raw material liquid to water is preferably 1:0.5-1, more preferably 1:0.6-0.8. The present application does not have special limitation to the concentrating method, and any concentrating method known to those skilled in the art can be used, such as vacuum concentration. The concentration temperature is preferably 60-80°C, more preferably 65-75°C. The vacuum degree of the concentration is preferably -0.1 to -0.08 MPa (gauge pressure), more preferably -0.09 to -0.08 MPa (gauge pressure). The present application does not have special limitation to the concentration time, and the concentration can be stopped when the ethyl acetate content in the obtained sucralose-6-acetate aqueous solution is less than 0.5 g / L. By controlling the residual amount of ethyl acetate in the sucralose-6-acetate aqueous solution, the present application can avoid the generation of by-products such as acetic acid and ethanol from ethyl acetate in the subsequent alkaline hydrolysis step, and further improve the purity and yield of sucralose. In the present application, the beating mother liquor is preferably recycled for preparing the crude sucralose, and more preferably used for dissolving the first ethyl ester phase concentrate.

[0078] After obtaining the aqueous solution of sucralose-6-acetate, the present application mixes the aqueous solution of sucralose-6-acetate with alkali metal hydroxide to carry out alkaline hydrolysis reaction, and then filters the obtained reaction solution after neutralization to obtain a second aqueous phase. In the present application, 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 solution of alkali metal hydroxide, and the concentration of the aqueous solution of alkali metal hydroxide is preferably 10-40 wt%, more preferably 20-35 wt%; the present application does not have special limitations on the amount of alkali metal hydroxide, which can only ensure that the pH value during the alkaline hydrolysis reaction is 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 of the alkaline hydrolysis reaction is preferably 3-6h, more preferably 3.5-5.5h, and further preferably 4-5h. The present application carries out alkaline hydrolysis reaction under the above conditions, so that sucralose diester can be hydrolyzed to generate sucralose, sucralose-6-acetate can be dechlorinated and hydrolyzed to generate sucralose, and the generation of by-products due to too high pH value or too high temperature of the alkaline hydrolysis reaction can also be avoided. Compared with using pure sucralose-6-acetate as raw material, the yield of sucralose is significantly improved, and the aqueous solution of crude sucralose-6-acetate does not need to be purified, which greatly shortens the process flow and reduces the production cost. In the present application, the acid for neutralization preferably includes hydrochloric acid, and the concentration of the hydrochloric acid is preferably 15-35 wt%, more preferably 20-30 wt%. The present application does not have special limitations on the amount of the acid, which can only neutralize the system to a pH value of 6.8-7. In the present application, the temperature of the neutralization and filtration is independently preferably 50-70℃, more preferably 55-65℃, and further preferably 60℃. After the alkaline hydrolysis is completed, viscous material will be generated, and a large amount of sucralose will be mixed in the viscous material. The present application heats the reaction solution obtained by the alkaline hydrolysis reaction to 50-70℃ for neutralization, so that the sucralose mixed in the viscous material can be dissolved, and then hot filtration can remove insoluble substances such as carbon residue and tar, and can also avoid the coking of sucralose due to too high temperature.

[0079] After obtaining the second aqueous phase, the second aqueous phase is extracted with ethyl acetate to obtain a second ethyl acetate phase and a third aqueous phase. In the present application, the number of times of ethyl acetate extraction is preferably 4-7; the volume ratio of the second aqueous phase to ethyl acetate in single ethyl acetate extraction is preferably 1:1-3, more preferably 1:1.5-2.5; the present application preferably combines the ethyl acetate phases obtained by the first 1-2 times of ethyl acetate extraction as the second ethyl acetate phase; preferably, the ethyl acetate phases obtained by the third 7 times of ethyl acetate extraction are used for the ethyl acetate extraction of the second aqueous phase in the next batch of sucralose crude preparation process, specifically, the ethyl acetate phase obtained by the third time of ethyl acetate extraction is used for the first time of ethyl acetate extraction of the second aqueous phase in the next batch of sucralose crude preparation process, the ethyl acetate phase obtained by the fourth time of ethyl acetate extraction is used for the second time of ethyl acetate extraction of the second aqueous phase in the next batch of sucralose crude preparation process, the ethyl acetate phase obtained by the fifth time of ethyl acetate extraction is used for the third time of ethyl acetate extraction of the second aqueous phase in the next batch of sucralose crude preparation process, the ethyl acetate phase obtained by the sixth time of ethyl acetate extraction is used for the fourth time of ethyl acetate extraction of the second aqueous phase in the next batch of sucralose crude preparation process, and the ethyl acetate phase obtained by the seventh time of ethyl acetate extraction is used for the fifth time of ethyl acetate extraction of the second aqueous phase in the next batch (i.e., the ethyl acetate phases obtained by the third 7 times of ethyl acetate extraction are used for the first 5 times of ethyl acetate extraction of the second aqueous phase in the next batch of sucralose crude preparation process, respectively); the sixth and seventh times of ethyl acetate extraction of the second aqueous phase of the next batch of sucralose crude are preferably carried out using pure ethyl acetate. In the present application, the content of sucralose in the third aqueous phase is preferably <0.5 g / L.

[0080] After obtaining the second ethyl ester phase, the second ethyl ester phase is washed with water to obtain a fourth water phase and a third ethyl ester phase, respectively; the fourth water phase is used in step (b) for dissolving the first ethyl ester phase concentrate. In the present application, the number of water washing is preferably 3-6 times; the volume ratio of the second ethyl ester phase to the single water used for water washing is preferably 1:0.1-0.3, more preferably 1:0.15-0.25; the water phase obtained by the first water washing is preferably used as the fourth water phase, and the water phases obtained by the second to sixth water washings are preferably used for the water washing of the second ethyl ester phase in the preparation process of the next batch of sucralose crude product, specifically, the water phase obtained by the second water washing is used for the first water washing of the second ethyl ester phase in the preparation process of the next batch of sucralose crude product, the water phase obtained by the third water washing is used for the second water washing of the second ethyl ester phase in the preparation process of the next batch of sucralose crude product, the water phase obtained by the fourth water washing is used for the third water washing of the second ethyl ester phase in the preparation process of the next batch of sucralose crude product, the water phase obtained by the fifth water washing is used for the fourth water washing of the second ethyl ester phase in the preparation process of the next batch of sucralose crude product, and the water phase obtained by the sixth water washing is used for the fifth water washing of the second ethyl ester phase in the preparation process of the next batch of sucralose crude product (i.e., the water phases obtained by the second to sixth water washings are used for the first to fifth water washings of the third ethyl ester phase in the preparation process of the next batch of sucralose crude product, respectively), and the sixth water washing of the second ethyl ester phase in the preparation process of the next batch of sucralose crude product is preferably performed using pure water.

[0081] After obtaining the third ethyl ester phase, the third ethyl ester phase is mixed with ethyl acetate to remove water by azeotropy to obtain a third ethyl ester phase concentrate; the third ethyl ester phase concentrate is mixed with ethyl acetate to obtain a fourth ethyl ester phase. The concentration method in the present application is not particularly limited, and any concentration method known to those skilled in the art can be used, specifically, vacuum concentration; the concentration temperature is preferably 60-80°C, more preferably 65-75°C; the vacuum degree of the concentration is preferably -0.1 to -0.08 MPa (gauge pressure), more preferably -0.09 to -0.08 MPa (gauge pressure); the concentration time in the present application is not particularly limited, and the concentration can be performed until the water content of the third ethyl ester phase concentrate is <0.5 wt%. The amount of ethyl acetate used in the present application is not particularly limited, and the sugar degree of the fourth ethyl ester phase is 40-60%, more preferably 45-55%.

[0082] After obtaining the fourth ethyl ester phase, the fourth ethyl ester phase is crystallized to obtain the crude sucralose and the fifth ethyl ester phase, respectively. In the present application, the temperature for the crystallization is preferably 40-60°C, more preferably 45-55°C; the time for the crystallization is preferably 12-30h, more preferably 15-25h. The solubility of sucralose in ethyl acetate is low, and the fat-soluble caramel impurities in the system are introduced into ethyl acetate during the recycling of the fourth and fifth aqueous phases, which can significantly increase the solubility of sucralose in ethyl acetate, and the impurities in the system are balanced by extraction, water washing and recycling, so that sucralose is enriched and crystallized in ethyl acetate. Moreover, the crystallization of sucralose at the above temperature has the following two advantages: 1) more sucralose can be obtained without being mixed with more fat-soluble impurities; 2) sucralose is not caramelized due to the high crystallization temperature, thereby improving the yield of sucralose. After the crystallization is completed, the present application preferably further comprises solid-liquid separation to obtain the crude sucralose and the fifth ethyl ester phase, respectively. The present application does not have special limitations on the solid-liquid separation method, and the solid-liquid separation method well known to those skilled in the art can be used, such as filtration, suction filtration or pressure filtration.

[0083] After obtaining the fifth ethyl ester phase, the fifth ethyl ester phase is water washed to obtain the fifth aqueous phase and the sixth ethyl ester phase, respectively; the fifth aqueous phase is recycled to step (b) to dissolve the first ethyl ester phase concentrate. The present application does not have special limitations on the number of water washings, and the content of sucralose in the sixth ethyl ester phase obtained by the last water washing is <0.1g / L, specifically 4-8 times. In the present application, the volume ratio of the fifth ethyl ester phase to the single water washing is preferably 1:0.5-1, more preferably 1:0.6-0.8. In the present application, the sixth ethyl ester phase is preferably concentrated to obtain recovered ethyl acetate and sugar residue, and the sugar residue is preferably treated as solid waste. After the crystallization is completed, there are more fat-soluble impurities in the fifth ethyl ester phase, and the solubility of sucralose in water is high, and the water washing method can recover the uncrystallized sucralose into the fifth aqueous phase, which can improve the yield of sucralose and recycling, and also can remove the fat-soluble impurities in the sucralose crystals to improve the purity.

[0084] The water-soluble impurities and the fat-soluble impurities are all sucrose produced in a series of reaction processes, and thus have similar main body structures to the sucralose, so that the water-soluble impurities, the fat-soluble impurities and the sucralose all have certain mutual solubility. The present application is to utilize the relationship among the three, and to select water and ethyl acetate as the solvents for removing the water-soluble impurities and the fat-soluble impurities, so as to utilize the fact that the two solvents can both dissolve and entrain the sucralose, to realize the exchange of the sucralose in the two solvents, and to make the sucralose enriched in the ethyl acetate, and to obtain the sucralose crude product by crystallization. Specifically, the solubility of the sucralose in the ethyl acetate is much smaller than the solubility in water, so that in the pretreatment process, the present application retains more fat-soluble impurities in the system. After the alkaline hydrolysis reaction, the sucralose is extracted from the alkaline hydrolysis solution by using multiple batches and multiple times of ethyl acetate. At this time, the concentration of the sucralose in the multiple times of extraction ethyl acetate presents a gradient decrease phenomenon, and the sucralose content in the ethyl acetate phase obtained by the first two times of extraction is relatively high, and is used as the raw material for the crystallization of the sucralose. The remaining batches of the ethyl acetate phase are used for the extraction of the next batch of alkaline hydrolysis solution, so as to obtain a saturated sucralose ethyl acetate solution. The content of the water-soluble impurities will affect the crystallization of the sucralose in the ethyl acetate phase, so that the ethyl acetate phase containing the sucralose in the first two times needs to be washed by a small amount of pure water for multiple times, so as to remove the water-soluble impurities therein. The concentration of the sucralose in the water phase obtained by the water washing also decreases with the increase of the water washing times, and in order to recover the part of the sucralose, the water washing liquid (the fourth water phase) with the highest concentration of the sucralose after the first water washing is reused to be mixed and dissolved with the first ethyl acetate phase concentrate, and the remaining water washing liquid is used for the water washing of the second ethyl acetate phase of the next batch of sucralose. The purpose of the concentration and drying treatment of the third ethyl acetate phase obtained after the water washing is to remove the moisture in the system, because the residual moisture will increase the difficulty of the crystallization of the sucralose in the ethyl acetate. After the concentration and drying, fresh ethyl acetate needs to be added for further concentration and drying, so as to remove the moisture, and at this time, the third ethyl acetate concentrate is dissolved in fresh ethyl acetate to a specific brix, and the fourth ethyl acetate phase obtained can be crystallized to obtain the sucralose crude product.

[0085] After obtaining the beating and decoloring target product liquid, the present application concentrates the beating and decoloring target product liquid, and crystallizes the obtained beating and decoloring target product concentrate liquid to obtain a first crystallization target product and a primary crystallization mother liquor. In the present application, the concentration temperature is preferably 60-80°C, more preferably 65-75°C; the concentration vacuum is preferably -0.1 to -0.08 MPa (gauge pressure), more preferably -0.09 to -0.08 MPa (gauge pressure); the concentration time is not particularly limited in the present application, and the concentration can be stopped when the sugar content of the obtained beating and decoloring target product concentrate liquid is 40-65%, more preferably 45-60%, and further preferably 50-55%; the concentration under the above conditions can avoid high-temperature coking of sucralose; and the beating and decoloring target product concentrate liquid with too high or too low sugar content is not easy to crystallize. In the present application, the first crystallization temperature is preferably room temperature, and the first crystallization time is preferably 8-16 h, more preferably 10-15 h, and further preferably 12-13 h. After the first crystallization, the present application preferably further comprises solid-liquid separation of the obtained first crystallization system to obtain a first crystallization target product and a primary crystallization mother liquor. The solid-liquid separation method is not particularly limited in the present application, and a method well known to those skilled in the art can be used, such as filtration, suction filtration, or pressure filtration. In the present application, the primary crystallization mother liquor is preferably recycled to prepare the crude sucralose, and more preferably used to remove water by azeotropy after mixing with the third ethyl ester.

[0086] After obtaining the first crystallization target product, the present application dissolves the first crystallization target product in water, and crystallizes the obtained first crystallization target product aqueous solution to obtain a second crystallization target product and a secondary crystallization mother liquor; and the secondary crystallization mother liquor is recycled to dissolve the beating target product in step (1). In the present application, the dissolution temperature is preferably 40-60°C, more preferably 45-55°C, and further preferably 50°C. In the present application, the sugar content of the first crystallization target product aqueous solution is preferably 40-65%, more preferably 45-60%, and further preferably 50-55%. In the present application, the second crystallization temperature is preferably room temperature, and the second crystallization time is preferably 8-16 h, more preferably 10-15 h, and further preferably 12-13 h. After the second crystallization, the present application preferably further comprises solid-liquid separation of the obtained second crystallization system to obtain a second crystallization target product and a secondary crystallization mother liquor. The solid-liquid separation method is not particularly limited in the present application, and a method well known to those skilled in the art can be used, such as filtration, suction filtration, or pressure filtration.

[0087] After obtaining the second crystallization target product, the present application dissolves the second crystallization target product in water, and then carries out solid-liquid separation on the obtained second crystallization target product aqueous solution after active carbon decolorization to obtain a second crystallization decolorization target product aqueous solution and recovered active carbon, respectively; the second crystallization decolorization target product aqueous solution is concentrated, and the obtained second crystallization decolorization target product concentrate is subjected to third crystallization to obtain a third crystallization target product and a third crystallization mother liquor, respectively; the third crystallization target product is dried to obtain a sucralose fine product; and the third crystallization mother liquor is recycled to step (3) for dissolving the first crystallization target product, and the recovered active carbon is recycled to step (1) for active carbon decolorization of the pulping target product aqueous solution. In the present application, the temperature of the dissolving is preferably 40-60°C, more preferably 45-55°C, and further preferably 50°C. In the present application, the sugar degree of the second crystallization target product aqueous solution is preferably 20-30%, more preferably 22-28%, and further preferably 24-26%. In the present application, the active carbon is preferably plant active carbon, and more preferably includes at least one of coconut shell active carbon and nut shell active carbon; coal-based active carbon will leave sulfur impurities, which will affect the product taste of sucralose, and the plant active carbon used in the present application has low sulfur content and will not affect the product quality of sucralose. In the present application, the mass of the active carbon is preferably 0.5-1% of the dry weight of the sucralose coarse product, more preferably 0.6-0.9%, and further preferably 0.7-0.8%; the temperature of the active carbon decolorization is preferably 40-50°C, and more preferably 45°C; and the time of the active carbon decolorization is preferably 5-10 min, and more preferably 6-8 min. The purpose of the active carbon decolorization is to remove residual water-soluble impurities and improve the purity and quality of the sucralose fine product. The present application does not have special limitations on the solid-liquid separation method, and any solid-liquid separation method known to those skilled in the art can be used, such as filtration, suction filtration, or pressure filtration. In the present application, the concentration temperature is preferably 60-80°C, and more preferably 65-75°C; and the vacuum degree of the concentration is preferably -0.1 to -0.08 MPa (gauge pressure), and more preferably -0.09 to -0.08 MPa (gauge pressure). The present application does not have special limitations on the concentration time, and the concentration can be stopped when the sugar degree of the obtained second crystallization decolorization target product concentrate is 40-65%, more preferably 45-60%, and further preferably 50-55%. In the present application, the temperature of the third crystallization is preferably 30-50°C, and more preferably 35-45°C; and the time of the third crystallization is preferably 4-12 h, and more preferably 5-10 h. After the third crystallization is completed, the present application preferably further includes carrying out solid-liquid separation on the obtained crystallization system to obtain a third crystallization target product and a third crystallization mother liquor, respectively. The present application does not have special limitations on the solid-liquid separation method, and any solid-liquid separation method known to those skilled in the art can be used, such as filtration, suction filtration, or pressure filtration.In this invention, the drying temperature is preferably 40-50°C, more preferably 45°C, and the drying time is preferably 8-12 hours, more preferably 10 hours.

[0088] The technical solutions of this invention will be clearly and completely described below with reference to the embodiments thereof. Obviously, the described embodiments are only a part of the embodiments of this invention, and not all of them. All other embodiments obtained by those skilled in the art based on the embodiments of this invention without creative effort are within the scope of protection of this invention.

[0089] The content of each substance in the following examples and comparative examples was determined by high performance liquid chromatography (HPLC) under the following conditions using the external standard method. The analytical conditions for HPLC were as follows: Shimadzu HPLC system equipped with RID-10A differential refractive index detector, LC-10ADVP high-pressure pump, and CTO-10ASVP incubator; chromatographic column: Agilent XDB C18 column (250mm × 4.6mm, 5μm); mobile phase: methanol-0.125wt% dipotassium hydrogen phosphate aqueous solution (4:6, v / v); column temperature: 40℃; mobile phase flow rate: 1.0mL / min; wherein, methanol (chromatographic grade), dipotassium hydrogen phosphate (analytical grade), and water were ultrapure water.

[0090] The following examples and comparative examples illustrate the preparation method of the raw material solution (denoted as the first aqueous solution): using sucrose as the raw material, DMF as the solvent, organotin as the catalyst, and acetic anhydride as the acylating agent, a solution containing sucrose-6-acetate was prepared; then the obtained solution containing sucrose-6-acetate was successively subjected to chlorination (thionyl chloride), neutralization with ammonia water, vacuum concentration to dryness, and dissolution with water to obtain the raw material solution.

[0091] Example 1

[0092] use Figures 1-2 The process flow diagram shown illustrates the preparation of refined sucralose, with the specific steps as follows:

[0093] (1) Extraction step: Add 0.9L of ethyl acetate to 3L of the first aqueous solution, stir and extract for 15min at 50℃, separate the phases to obtain an organic phase and an aqueous phase. Repeat the above extraction step 6 times with the aqueous phase. After extraction, the ester phases are combined as the first ethyl ester phase, and the aqueous phase obtained from the last extraction is the first aqueous phase (the content of sucralose-6-acetate is 0.07g / L, and the first aqueous phase is used for high-salt wastewater treatment). The composition of the first aqueous solution is shown in Table 1:

[0094] Table 1 Composition of the first aqueous solution

[0095] Component Content Sucralose-6-acetate 55.2 g / L Sucralose diester 5.0 g / L Tetrachlorosucrose-6-acetate 5.3 g / L NH4CI 81.7 g / L Other organic impurities 33.5 g / L Water 81.4％

[0096] (2) Concentration step: the first ethyl ester phase was concentrated to dryness (abbreviated as concentration and drying) at 80°C and -0.08 MPa, and water (1800 mL) was added to the obtained first ethyl ester phase concentrate and mixed, and concentrated to 1.8 L under the above conditions to obtain a sucralose-6-acetate aqueous solution (ethyl acetate content was 0.40 g / L), which was then transferred to a three-necked flask.

[0097] (3) Alkaline hydrolysis step: the obtained sucralose-6-acetate aqueous solution was cooled to 1°C, and then a 32 wt% sodium hydroxide aqueous solution was added dropwise and mixed uniformly, and alkaline hydrolysis was carried out at 1°C for 5 h, and the pH value of the system was maintained at 12.2 during the alkaline hydrolysis, and after the alkaline hydrolysis was completed, the system was heated to 50°C, and then a 30 wt% dilute hydrochloric acid was added dropwise to adjust the pH value to 7.5, and filtration was carried out to obtain a second aqueous phase (2 L, sucralose-6-acetate content was 0.04 g / L) and a filter residue (solid waste treatment).

[0098] (4) Separation step: 4 L of ethyl acetate was added to the second aqueous phase, and stirring extraction was carried out at 50°C for 15 min, and the obtained aqueous phase was repeatedly subjected to the above extraction operation, and a total of 6 times of extraction was carried out, and the ester phases obtained by the first and second extractions were combined as a second ethyl ester phase (8.6 L), and the ester phases obtained by the third to sixth ethyl acetate extractions were used for the first to fourth ethyl acetate extractions of the second aqueous phase in the preparation process of the next batch of sucralose crude product, respectively. Water washing was carried out on the second ethyl ester phase by adding 1.6 L of water, and the water washing was carried out for 6 times, and the aqueous phase obtained by the first water washing was a fourth aqueous phase, which was used to replace water to mix with the first ethyl ester phase concentrate in step (2); the aqueous phases obtained by the second to sixth water washings were used for the first to fifth water washings of the second ethyl ester phase in the preparation process of the next batch of sucralose crude product, respectively, and the ester phase obtained after the water washing was completed was a third ethyl ester phase. The third ethyl ester phase was concentrated to dryness at 70°C and -0.1 MPa (gauge pressure), and ethyl acetate (0.9 L was added each time, and the addition was carried out for 3 times) was added during the concentration to dryness to remove water to ensure that the water was completely removed, and ethyl acetate was added to the obtained third ethyl ester phase concentrate to adjust the sugar degree Bx to 45% to obtain a fourth ethyl ester phase.

[0099] (5) Crystallization step: the fourth ethyl ester phase was crystallized at 45°C for 24 h, and suction filtration was carried out to obtain sucralose crude product and a fifth ethyl ester phase 1.3 L (which was used for 4 times of equilibrium), respectively; the fifth ethyl ester phase was water washed for 6 times (the water use amount was 0.6 L each time), and the ester phase after the water washing was a sixth ester phase (sucralose content was 0.02 g / L), and the sixth ester phase was concentrated to dryness to obtain recovered ethyl acetate and sugar residue, respectively; the aqueous phases were combined as a fifth aqueous phase, and the fifth aqueous phase was used to replace water to mix with the first ethyl ester phase concentrate in step (2).

[0100] (6) Beating and decoloring: ethyl acetate is added to the crude sucralose, and beating is performed at room temperature for 10 minutes. Filtration is performed to obtain a beating mother liquor and a beating target product. The beating mother liquor is returned to step (2) to dissolve the first ethyl acetate phase concentrate. The beating target product is dissolved in water at 45°C. Coconut activated carbon is added to the obtained beating target product aqueous solution (sugar content of 20%) to perform decoloring at 40°C for 10 minutes to obtain a beating and decoloring target product liquid. The ratio of the dry weight of the crude sucralose to the volume of the ethyl acetate is 1 kg: 1 L. The mass of the coconut activated carbon is 0.5% of the mass of the dry crude sucralose.

[0101] (7) First crystallization: the beating and decoloring target product liquid is concentrated at 80°C and -0.08 MPa (gauge pressure). The obtained beating and decoloring target product concentrate (sugar content of 40%) is first crystallized at room temperature for 16 hours. Filtration is performed to obtain a first crystallization target product and a primary crystallization mother liquor. The primary crystallization mother liquor is used in step (4) to perform azeotropic water removal after being mixed with the third ethyl acetate phase.

[0102] (8) Second crystallization: the first crystallization target product is dissolved in water at 60°C. The obtained first crystallization target product aqueous solution (sugar content of 65%) is second crystallized at room temperature for 8 hours to obtain a second crystallization target product and a secondary crystallization mother liquor. The secondary crystallization mother liquor is returned to step (6) to dissolve the beating target product.

[0103] (9) Third crystallization: the second crystallization target product is dissolved in water at 50°C. Coconut activated carbon (the mass of the activated carbon is 1% of the dry crude sucralose) is added to the obtained second crystallization target product aqueous solution (sugar content of 25%) to perform decoloring at 45°C for 5 minutes. Filtration is performed to obtain a second crystallization and decoloring target product aqueous solution and recovered activated carbon. The second crystallization and decoloring target product aqueous solution is concentrated at 60°C and -0.1 MPa (gauge pressure). The obtained second crystallization and decoloring target product concentrate (sugar content of 65%) is third crystallized at 50°C for 4 hours to obtain a third crystallization target product and a tertiary crystallization mother liquor. The third crystallization target product is dried to obtain fine sucralose. The tertiary crystallization mother liquor is returned to step (3) to dissolve the first crystallization target product. The recovered activated carbon is returned to step (1) to perform activated carbon decoloring on the beating target product aqueous solution.

[0104] (10) Recycling: The fourth aqueous phase, the fifth aqueous phase, the second ethyl ester phase, the water-washed second ethyl ester phase, and the ethyl acetate-extracted second aqueous phase are recycled 17 times according to the operations of steps (1) to (9) (denoted as recycling 0 times). In step (2), the operation of "mixing the obtained first ethyl ester phase concentrate with water (1800 mL)" is modified to "mixing the obtained first ethyl ester phase, the fourth aqueous phase, the fifth aqueous phase, and the beating mother liquor". In step (4), the operation of "adjusting the sugar content Bx of the obtained third ethyl ester phase concentrate to 43% by adding ethyl acetate" is replaced by "adding the once-crystallized mother liquor to the obtained third ethyl ester phase concentrate, concentrating at 80°C and -0.08 MPa (gauge pressure) to a water content of 0.4 wt%, and then adding ethyl acetate to adjust the sugar content Bx to 43%". The first to fourth ethyl acetate-extracted second aqueous phases are obtained from the third to sixth ethyl acetate-extracted second aqueous phases of the previous batch of sucralose crude product, the fifth and sixth ethyl acetate-extracted second aqueous phases are obtained using pure ethyl acetate, the first to fifth water-washed second ethyl ester phases are obtained from the second to sixth water-washed second ethyl ester phases of the previous batch of sucralose crude product, and the sixth water-washed second ethyl ester phase is obtained using pure water. In step (6), the operation of "dissolving the beating target product in water at 60°C" is replaced by "dissolving the beating target product in water and the twice-crystallized mother liquor at 60°C", and the coconut shell activated carbon in step (6) is replaced by the recovered activated carbon obtained in step (9). In step (8), the operation of "placing the first crystallized target product in water" is replaced by "placing the first crystallized target product in water and the thrice-crystallized mother liquor". The purity and yield data of the sucralose fine product obtained are shown in Table 2:

[0105] Table 2 Purity and yield of sucralose fine product

[0106]

[0107] Note: Yield = mass of sucralose / mass of sucralose-6-acetate completely converted into sucralose x 100%. In the first aqueous solution, both sucralose diester and sucralose-6-acetate can be converted into sucralose after alkaline hydrolysis, and the theoretical maximum yield in Example 1 is 117.48%.

[0108] As shown in Table 2, each mother liquor needs to be recycled at least 4 times to stabilize the yield of the sucralose fine product, and the yield is still above 116% after 17 times of recycling.

[0109] Example 2

[0110] The sucralose fine product is prepared according to the method of Example 1, with the difference from Example 1 being:

[0111] (1) Extraction step: 1.2 L of ethyl acetate was added to 3 L of the first aqueous solution, and the mixture was stirred at 45°C for 10 min to extract, and then the organic phase and the aqueous phase were separated. The above extraction step was repeated 6 times with the aqueous phase, and after the extraction was completed, the ester phases were combined as the first ethyl acetate phase. The aqueous phase obtained in the last extraction was the first aqueous phase (sucralose-6-acetate content: 0.05 g / L, and the first aqueous phase was subjected to high-salt wastewater treatment). The main components of the first solution used are shown in Table 3:

[0112] Table 3: Composition of the first solution

[0113] Component Content Sucralose-6-acetate 51.4 g / L Sucralose diester 5.7 g / L Tetrachlorosucrose-6-acetate 4.8 g / L NH4CI 84.6 g / L Other organic impurities 35.1 g / L Water 82.7％

[0114] (2) Concentration and drying step: The first ethyl acetate phase was concentrated to dryness (abbreviated as concentration and drying) at 80°C and -0.08 MPa. Water (1800 mL) was added to the obtained first ethyl acetate concentrate, and the mixture was concentrated to 1.7 L under the above conditions to obtain a sucralose-6-acetate aqueous solution (ethyl acetate content: 0.26 g / L), which was then transferred to a three-necked flask.

[0115] (3) Alkaline hydrolysis step: The obtained sucralose-6-acetate aqueous solution was cooled to 2°C, and then a 32 wt% aqueous sodium hydroxide solution was added dropwise to the mixture and stirred to mix uniformly. The mixture was subjected to alkaline hydrolysis at 2°C for 5 h while maintaining the pH value of the system at 12.1. After the alkaline hydrolysis was completed, the mixture was heated to 50°C, and then a 30 wt% dilute hydrochloric acid solution was added dropwise to adjust the pH value to 7. Filtration was performed to obtain a second aqueous phase (1.90 L, sucralose-6-acetate content: 0.01 g / L) and a filter residue (solid waste treatment).

[0116] (4) Separation step: 4 L of ethyl acetate was added to the second aqueous phase, and the mixture was stirred at 45°C for 10 min to extract. The above extraction operation was repeated 6 times with the aqueous phase obtained. The ester phases obtained in the first and second extractions were combined as a second ethyl acetate phase (8.5 L). The ester phases obtained in the third to sixth extractions were used in the first to fourth ethyl acetate extractions of the second aqueous phase in the preparation process of the next batch of sucralose crude product, respectively. 1.8 L of water was added to the second ethyl acetate phase to perform water washing 6 times. The aqueous phase obtained in the first water washing was a fourth aqueous phase, which was used to replace water in the mixing of the first ethyl acetate concentrate in step (2). The aqueous phases obtained in the second to sixth water washings were used in the first to fifth water washings of the second ethyl acetate phase in the preparation process of the next batch of sucralose crude product, respectively. After the water washing was completed, the ester phase obtained was a third ethyl acetate phase. The third ethyl acetate phase was concentrated to dryness at 75°C and -0.1 MPa (gauge pressure). Ethyl acetate (0.8 L each time) was added 3 times during the concentration and drying to remove water completely. Ethyl acetate was added to the obtained third ethyl acetate concentrate to adjust the sugar degree Bx to 44% to obtain a fourth ethyl acetate phase.

[0117] (5) Crystallization step: the fourth ethyl ester phase was crystallized at 40 °C for 20 h, and was extracted by filtration, to obtain the crude sucralose and the fifth ethyl ester phase 1.3 L (after 4 times of balance) respectively; the fifth ethyl ester phase was washed with water for 6 times (the amount of water used was 0.55 L each time), and the ester phase after water washing was the sixth ester phase (the sucralose content was 0.06 g / L), and the sixth ester phase was concentrated dry to obtain the recovered ethyl acetate and the sugar residue respectively; the water phase was combined as the fifth water phase, and the fifth water phase was used to replace water to mix with the first ethyl ester phase concentrate in step (2).

[0118] In step (6), the ratio of the dry weight of the crude sucralose to the volume of ethyl acetate was 1 kg: 1.5 L, and the sugar content of the slurry target product aqueous solution was 30%.

[0119] In step (7), the concentration was carried out at 60 °C and -0.1 MPa (gauge pressure), the sugar content of the slurry decolorized target product concentrate was 50%, and the first crystallization time was 16 h.

[0120] In step (8), the dissolving temperature was 50 °C, the sugar content of the first crystallization target product aqueous solution was 55%, and the second crystallization time was 12 h.

[0121] In step (9), the dissolving temperature was 40 °C, the sugar content of the second crystallization target product aqueous solution was 20%, the activated carbon mass was 0.5% of the dry weight of the crude sucralose, the decolorization time was 10 min, the concentration was carried out at 70 °C and -0.09 MPa (gauge pressure), the sugar content of the second crystallization decolorized target product concentrate was 40%, the third crystallization was carried out at 30 °C for 12 h, and the drying was carried out at 50 °C for 8 h.

[0122] In step (10), the purity and yield data of the sucralose fine product obtained by 17 times of recycling were shown in Table 4:

[0123] Table 4 Purity and yield of sucralose fine product

[0124]

[0125]

[0126] Note: The theoretical yield was 119.08%.

[0127] Example 3

[0128] The sucralose fine product was prepared according to the method of Example 1, and the difference from Example 1 was that:

[0129] (1) Extraction step: 0.85 L of ethyl acetate was added to 3 L of the first aqueous solution, and the extraction was stirred at 50°C for 10 min, and the phases were separated to obtain an organic phase and an aqueous phase. The aqueous phase was repeatedly subjected to the above extraction step for 6 times. After the extraction was completed, the ester phases were combined as the first ethyl acetate phase, and the aqueous phase obtained in the last extraction was the first aqueous phase (the content of sucralose-6-acetate was 0.06 g / L, and the first aqueous phase was subjected to high-salt wastewater treatment). The main components of the first solution are shown in Table 5:

[0130] Table 5: Composition of the first solution

[0131] Component Content Sucralose-6-acetate 60.1 g / L Sucralose diester 4.8 g / L Tetrachlorosucrose-6-acetate 4.7 g / L NH4Cl 80.3 g / L Other organic impurities 30.4 g / L Water 82.7％

[0132] (2) Concentration and drying step: the first ethyl acetate phase was concentrated to dryness under vacuum at 80°C and -0.08 MPa (simplified as concentration and drying). Water (1800 mL) was added to the obtained first ethyl acetate concentrate and mixed, and the mixture was concentrated to 1.8 L under the above conditions to obtain a sucralose-6-acetate aqueous solution (the content of ethyl acetate was 0.41 g / L), which was then transferred to a three-necked flask.

[0133] (3) Alkaline hydrolysis step: the obtained sucralose-6-acetate aqueous solution was cooled to 3°C, and then a 32 wt% aqueous sodium hydroxide solution was added dropwise and mixed uniformly. The mixture was subjected to alkaline hydrolysis at 3°C for 6 h, and the pH value of the system was maintained at 12.5 during the hydrolysis. After the hydrolysis was completed, the mixture was heated to 45°C, and then a 30 wt% dilute hydrochloric acid was added dropwise to adjust the pH value to 7. Filtration was performed to obtain a second aqueous phase (2 L, the content of sucralose-6-acetate was 0.05 g / L) and a filter residue (solid waste treatment).

[0134] (4) Separation step: 4.1 L of ethyl acetate was added to the second aqueous phase, and the extraction was stirred at 50°C for 10 min. The obtained aqueous phase was repeatedly subjected to the above extraction operation for 6 times. The ester phases obtained in the first and second extractions were combined as the second ethyl acetate phase (8.5 L). The ester phases obtained in the third to sixth ethyl acetate extractions were used for the first to fourth ethyl acetate extractions of the second aqueous phase in the preparation process of the next batch of sucralose crude product, respectively. 1.7 L of water was added to the second ethyl acetate phase for water washing, and the water washing was performed for 6 times. The aqueous phase obtained in the first water washing was the fourth aqueous phase, which was used to replace water and mix with the first ethyl acetate concentrate in step (2). The aqueous phases obtained in the second to sixth water washings were used for the first to fifth water washings of the second ethyl acetate phase in the preparation process of the next batch of sucralose crude product, respectively. After the water washing was completed, the ester phase was the third ethyl acetate phase. The third ethyl acetate phase was concentrated and dried under vacuum at 80°C and -0.09 MPa (gauge pressure). Ethyl acetate (0.8 L each time) was added for 3 times during the concentration and drying to ensure that the water was completely removed. Ethyl acetate was added to the obtained third ethyl acetate concentrate to adjust the sugar content Bx to 41% to obtain the fourth ethyl acetate phase.

[0135] (5) Crystallization step: the fourth ethyl ester phase was crystallized at 40 °C for 18 h, and was extracted by filtration, to obtain the crude sucralose and the fifth ethyl ester phase 1.1 L (after 4 times of balance) respectively; the fifth ethyl ester phase was washed by water for 6 times (0.55 L of water was used each time), and the ester phase after water washing was the sixth ester phase (the sucralose content was 0.07 g / L), the sixth ester phase was concentrated and dried to obtain the recovered ethyl acetate and the sugar residue respectively; the water phase was combined as the fifth water phase, which was used to replace water to mix with the first ethyl ester phase concentrate in step (2).

[0136] In step (6), the ratio of the dry weight of the crude sucralose to the volume of ethyl acetate was 1 kg: 1.2 L, and the sugar content of the slurry target product aqueous solution was 25%.

[0137] In step (7), the concentration was carried out at 70 °C and -0.09 MPa (gauge pressure), the sugar content of the slurry decolorized target product concentrate was 65%, and the first crystallization time was 8 h.

[0138] In step (8), the dissolving temperature was 40 °C, the sugar content of the first crystallization target product aqueous solution was 40%, and the second crystallization time was 16 h.

[0139] In step (9), the dissolving temperature was 60 °C, the sugar content of the second crystallization target product aqueous solution was 30%, the activated carbon mass was 0.7% of the dry weight of the crude sucralose, the decolorization time was 8 min, the concentration was carried out at 80 °C and -0.08 MPa (gauge pressure), the sugar content of the second crystallization decolorized target product concentrate was 55%, the third crystallization was carried out at 40 °C for 8 h, and the drying was carried out at 45 °C for 10 h.

[0140] In step (10), the purity and yield data of the sucralose fine product obtained by 17 times of recycling were shown in Table 6:

[0141] Table 6 Purity and yield of sucralose fine product

[0142]

[0143] Note: The theoretical yield was 114.79%.

[0144] Mother liquor recycling is one of the important means to improve the yield of target product and reduce production cost. The key to successful recycling is how to separate the impurities enriched in the repeated recycling process from the target product. Only by continuously separating the impurities from the target product and discharging the process system can the stable operation of the process be ensured. Therefore, at which step and in which way the impurities are separated and discharged is the focus of the process. The present application can effectively remove the impurities in the crude product and the impurities produced by oxidation in the crystallization mother liquor recycling process by ethyl acetate beating treatment of the crude sucralose, twice different stage activated carbon impurity removal and third crystallization.

[0145] Moreover, the present application found that if all the mother liquor produced in the purification process of sucralose is recycled, the impurities will be enriched, so that qualified sucralose cannot be obtained, and crystallization cannot be performed after multiple recycling. According to the different characteristics (such as solvent and impurity content) of the mother liquor produced in each preparation step, part of the mother liquor (beating mother liquor and first crystallization mother liquor) is used to prepare crude sucralose, and part of the mother liquor (second crystallization mother liquor and third crystallization mother liquor) is recycled for purification of crude sucralose, so that the recycling of the mother liquor is realized, and crystallization cannot be performed after multiple recycling. The yield of sucralose is significantly improved, and the loss of sucralose in the purification process is reduced.

[0146] In summary, the preparation method of sucralose can be effectively combined with the method of preparing crude sucralose by using a hydrolysis system, the recycling of the mother liquor formed during the preparation of sucralose can be realized, the problem of waste of mother liquor resources is solved, the amount of waste liquid is reduced, the recovery of sucralose is maximized, the yield of sucralose is significantly increased, and food-grade sucralose can be prepared in different forms, which significantly reduces the production cost and has high industrialization prospect.

[0147] The above examples are only used to help understand the method of the present application and its core idea. It should be noted that for ordinary skilled persons in the art, some improvements and modifications can be made to the present application without departing from the principles of the present application, and these improvements and modifications also fall within the protection scope of the claims of the present application. Various modifications of the examples are obvious to those skilled in the art, and the general principles defined herein can be implemented in other embodiments without departing from the spirit or scope of the present application. Therefore, the present application will not be limited to the examples shown herein, but will conform to the widest scope consistent with the principles and novel features disclosed herein.

Claims

1. A method for preparing a refined sucralose product, characterized in that, Includes the following steps: (1) The crude sucralose was mixed with ethyl acetate, and after pulping, solid-liquid separation was performed to obtain pulping mother liquor and pulping target product, respectively; The target product is dissolved in water, and the resulting aqueous solution of the target product is decolorized with activated carbon to obtain a decolorized target product solution; the pulping temperature is 20~40℃ and the time is 5~15min; the mass ratio of crude sucralose to the volume ratio of ethyl acetate is 1kg:1~1.5L. (2) The pulping and decolorizing target product liquid is concentrated, and the obtained pulping and decolorizing target product concentrate is subjected to first crystallization to obtain the first crystallized target product and the first crystallization mother liquor respectively. (3) Dissolve the first crystallization target product in water, and perform a second crystallization on the obtained first crystallization target product aqueous solution to obtain the second crystallization target product and the secondary crystallization mother liquor respectively; The secondary crystallization mother liquor is recycled in step (1) to dissolve the pulping target product; (4) Dissolve the second crystallized target product in water, decolorize the obtained second crystallized target product aqueous solution with activated carbon, and then separate the solid and liquid to obtain the second crystallized decolorized target product aqueous solution and the recovered activated carbon, respectively. The aqueous solution of the second crystallized decolorized target product is concentrated, and the resulting concentrated solution of the second crystallized decolorized target product is subjected to a third crystallization to obtain the third crystallized target product and the mother liquor of the third crystallization. The third crystallized target product is dried to obtain refined sucralose; the mother liquor of the third crystallization is recycled in step (3) to dissolve the first crystallized target product, and the recycled activated carbon is recycled in step (1) to decolorize the aqueous solution of the pulped target product. The method for preparing the crude sucralose product includes the following steps: (a) The feed solution is extracted with ethyl acetate to obtain a first ethyl ester phase and a first aqueous phase, respectively; the first ethyl ester phase is concentrated to obtain a first ethyl ester phase concentrate; the feed solution is an aqueous solution comprising sucralose-6-acetate, sucralose diester and tetrachlorosucralose-6-acetate; (b) The first ethyl ester phase concentrate was mixed with water and dissolved, and then concentrated to obtain an aqueous solution of sucralose-6-acetic acid ester; (c) The aqueous solution of sucralose-6-acetate is mixed with an alkali metal hydroxide to carry out an alkaline hydrolysis reaction. The resulting reaction solution is neutralized and then filtered to obtain a second aqueous phase. (d) The second aqueous phase was extracted with ethyl acetate to obtain a second ethyl ester phase and a third aqueous phase, respectively; (e) The second ethyl ester phase is washed with water to obtain a fourth aqueous phase and a third ethyl ester phase; the fourth aqueous phase is reused in step (b) to dissolve the first ethyl ester phase concentrate. (f) The third ethyl ester phase is mixed with ethyl acetate and subjected to azeotropic dehydration to obtain a concentrated third ethyl ester phase; the concentrated third ethyl ester phase is mixed with ethyl acetate to obtain a fourth ethyl ester phase; (g) The fourth ethyl ester phase is crystallized to obtain crude sucralose and the fifth ethyl ester phase, respectively; (h) The fifth ethyl ester phase is washed with water to obtain a fifth aqueous phase and a sixth ethyl ester phase; the fifth aqueous phase is recycled in step (b) to dissolve the first ethyl ester phase concentrate; The pulping mother liquor is used to dissolve the first ethyl ester phase concentrate; The mother liquor from the first crystallization is mixed with the third ethyl ester and then azeotropically dehydrated.

2. The preparation method according to claim 1, characterized in that, In step (1), the crude sucralose product comprises the following components in mass percentage: 85-95% sucralose, 0.5-1% sucralose-6-acetate, 1-3% ethyl acetate, and 1-13.5% caramel impurities.

3. The preparation method according to claim 1, characterized in that, In step (1), the dissolution temperature is 30~50℃; The sugar content of the target product aqueous solution after pulping is 20-40%.

4. The preparation method according to claim 1, characterized in that, In step (2), the sugar content of the pulping and decolorizing target product concentrate is 40-65%.

5. The preparation method according to claim 1 or 4, characterized in that, In step (2), the temperature of the first crystal is room temperature and the time is 8~16h.

6. The preparation method according to claim 1, characterized in that, In step (3), the melting temperature is 40~60℃; The sugar content of the aqueous solution of the first crystallized target product is 40-65%.

7. The preparation method according to claim 1 or 6, characterized in that, In step (3), the temperature of the second crystallization is room temperature and the time is 8~16h.

8. The preparation method according to claim 1, characterized in that, In step (4), the dissolution temperature is 40~60℃; The sugar content of the aqueous solution of the second crystallized decolorized target product is 20-30%.

9. The preparation method according to claim 1, characterized in that, In step (4), the sugar content of the second crystallized decolorized target product concentrate is 40-65%.

10. The preparation method according to claim 1 or 9, characterized in that, In step (4), the temperature of the third crystallization is 30~50℃ and the time is 4~12h.

11. The method according to claim 1, characterized in that, The sucralose content in the third, fourth, and fifth aqueous phases was independently <0.5 g / L.

12. The method according to claim 1, characterized in that, In step (a), the temperature of the ethyl acetate extraction is 40~60℃, and the number of extractions is 5~8; the volume ratio of the raw material liquid to the ethyl acetate used for a single ethyl acetate extraction is 1:0.2~0.

5.

13. The method according to claim 1, characterized in that, In step (b), the content of ethyl acetate in the aqueous solution of sucralose-6-acetate is <0.5 g / L.

14. The method according to claim 1, characterized in that, In step (c), the pH value of the alkaline hydrolysis reaction is 11~13, the temperature is 0~10℃, and the time is 3~6h.

15. The method according to claim 1, characterized in that, In step (c), the temperature for neutralization and filtration is independently 50~70°C.

16. The method according to claim 1, characterized in that, In step (d), the ethyl acetate extraction is performed 4 to 7 times; the volume ratio of the second aqueous phase to the ethyl acetate used in a single extraction is 1:1 to 3. The ethyl ester phases obtained from the first and second ethyl acetate extractions were combined as the second ethyl ester phase; The ethyl acetate phase obtained from the 3rd to 7th ethyl acetate extractions was used for the ethyl acetate extraction of the second aqueous phase in the next batch of crude sucralose preparation.

17. The method according to claim 11, characterized in that, In step (e), the number of water washes is 3 to 6; the volume ratio of the second ethyl ester phase to the water used in a single water wash is 1:0.1 to 0.

3. The aqueous phase obtained from the first water wash is taken as the fourth aqueous phase; The aqueous phase obtained from the 2nd to 6th water washes is used for washing the second ethyl ester phase in the next batch of crude sucralose preparation.

18. The method according to claim 1, characterized in that, In step (f), the water content of the third ethyl ester phase concentrate is <0.5 wt%.

19. The method according to claim 1, characterized in that, In step (f), the sugar content of the fourth ethyl ester phase is 40-60%.

20. The method according to claim 1 or 19, characterized in that, In step (g), the crystallization temperature is 40~60℃ and the time is 12~30h.

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