A fractional crystallization process of sucralose

Abstract

The present invention provides a process for fractional crystallization of sucralose. The sucrose acylation-chlorination reaction solution is catalytically treated with high-concentration sodium hydroxide to obtain a sucralose mixed solution. The mixed solution is filtered to remove residues and desolvated to obtain an aqueous solution of crude sucralose product. The aqueous solution is extracted step by step with a first and a second organic solvent, so that sucralose is highly enriched in the second organic solvent phase. After decolorization and concentration, a crude sucralose product is obtained. The third and fourth organic solvents are added step by step to completely dissolve it, and finally a "solvent-anti-solvent" crystallization system is formed. After a small amount of seed crystals are added thereto, sucralose crystals are efficiently obtained at room temperature under constant temperature. Through one-step "solvent-anti-solvent" fractional crystallization and one-step pure water recrystallization, a qualified sucralose product (purity > 98%) is obtained after drying. This process greatly simplifies the production steps of sucralose, shortens the three-step reaction of the traditional process to two steps, and at the same time streamlines the purification steps of sucralose, having better industrial value.

Description

Technical Field

[0001] The present invention relates to the field of sucralose crystallization separation, specifically to a method for highly purifying sucralose based on antisolvent crystallization technology, and belongs to the technical field of sucralose production. Background Art

[0002] Sucralose, commonly known as sucralose, is a kind of halogenated sucrose derivative. Sucralose is an artificial sweetener made from sucrose, and its sweetness is 400 - 800 times that of sucrose. Sucralose has been widely used in more than 400 kinds of foods. Low-calorie beverages are the largest market for artificial sweeteners, and low-calorie beverages will be the focus of future market promotion, which will undoubtedly greatly increase the market demand for sucralose. In recent years, the global production capacity, output and market demand of sucralose have been growing steadily. It has become the variety with the fastest growth rate of demand in the sweetening ingredient market, and the market development trend is promising.

[0003] The existing industrial synthesis route of sucralose mainly adopts the single-group protection method. The sucrose raw material needs to go through three chemical reaction processes including acylation, chlorination and alcoholysis, as well as more than 20 separation processes to obtain a qualified sucralose product. Its process flow is cumbersome and lengthy, with high production energy consumption, low efficiency and large solvent consumption, which seriously restricts the industrial production scale of sucralose and the development of the sucralose industry. The third step of base-catalyzed alcoholysis reaction in the sucralose production process is similar and repetitive to the second step of chlorination base quenching and neutralization reaction. The fundamental reason is that the separation efficiency of the intermediate sucralose-6-acetate is much greater than that of sucralose. Therefore, studying the high-efficiency purification technology of sucralose is of great significance for the production of sucralose.

[0004] There are many patent reports on the purification of sucralose at present. For example, US4980463 concentrates the alcoholysis reaction solution and makes it into an aqueous solution of crude sucralose. It uses methyl benzoate for primary extraction, then back extracts with water, followed by decolorization and concentration, and finally crystallizes to obtain pure sucralose. US5498709 uses ethyl acetate solvent to extract the aqueous solution of sucralose, then removes the residual N, N-dimethylformamide by washing with water, and finally concentrates and crystallizes to obtain sucralose. US7049435 uses two non-aromatic organic solvents to extract the aqueous solution of sucralose respectively, so that impurities are retained in the organic solvent and the aqueous phase, and high-purity sucralose is obtained by concentrating and crystallizing from another organic solvent phase. CN1330659 uses non-crystallization methods such as liquid-liquid extraction, extraction precipitation, chromatography or distillation with ethyl acetate and water to purify the crude sucralose solution, and then obtains pure sucralose through three or more steps of continuous crystallization and recycling of the mother liquor. US20090208747 slowly cools and crystallizes in a mixed alcohol solvent to obtain sucralose crystals. CN100567319 uses a mixed solvent of water and alcohol or a mixed solvent of water and ethyl acetate to crystallize sucralose. CN100591684 utilizes the differences in polarity and boiling point of the mixed solvent, concentrates the stronger polar / lower boiling point solvent, and crystallizes to obtain sucralose. CN112543760 extracts non-polar impurities in the aqueous solution of sucralose with ethyl acetate or isopropyl acetate, and the aqueous solution is concentrated and recrystallized to obtain sucralose crystals. However, the above reports all use the sucralose feed solution obtained by the alcoholysis process as the starting material for purification. Among them, the impurities gradually accumulated during the sucrose acylation and chlorination processes have been purified. The whole process requires prior purification of sucralose-6-acetate and one-step alcoholysis reaction, and the process flow is very complex. Summary of the Invention

[0005] The object of the present invention is to solve the above existing technical bottlenecks, and provide a production process for the antisolvent crystallization of sucralose. By using the antisolvent crystallization mechanism, it overcomes the problems of difficult crystallization and slow crystallization rate of the complex sucralose-impurity system, realizes the efficient crystallization and separation of sucralose, shortens the reaction steps, simplifies the purification process, and reduces the production cost of sucralose.

[0006] In order to achieve the above object, the technical solution of the present invention is:

[0007] A production process for the antisolvent crystallization of sucralose, the steps include:

[0008] In the first step, after the sucralose mixture solution is filtered to remove residues and concentrated to remove solvents, it is made into an aqueous solution of crude sucralose products with pure water, and the aqueous solution is further extracted step by step with the first and second organic solvents, so that sucralose is largely enriched in the second organic solvent phase. After decolorization and concentration, crude sucralose products are obtained.

[0009] In the second step, the third and fourth organic solvents are added step by step to completely dissolve the crude sucralose product, finally forming a "solvent-anti-solvent" sucralose precipitation crystallization system. After adding a small amount of seed crystals and stirring, a "solvent-anti-solvent" system is formed. Sucralose crystals are efficiently obtained at a constant temperature at room temperature, and then "solvent-anti-solvent" crystallization is carried out once to obtain solid powder of sucralose. It is dissolved in pure water, cooled for recrystallization, and dried to obtain a qualified sucralose product.

[0010] Further, the sucralose mixed solution in the first step refers to a mixed solution of sucralose obtained by slowly dropping 40-80 wt% aqueous sodium hydroxide solution to pH>10.5 and catalyzing for 1-5 h at -10~40 °C in a sucrose acylation-chlorination reaction solution, and quenching with 36 wt% hydrochloric acid. Its specific composition includes dozens of main chlorinated sucrose by-products such as 4,1',6'-trichlorosucrose, 4,6'-dichlorosucrose, 1',6'-dichlorosucrose, 6,4,6'-trichlorosucrose, 6,1',6'-trichlorosucrose, 2,4,1',6'-tetrachlorosucrose, and 6,4,1',6'-tetrachlorosucrose, as well as organic solvents such as carbon residue, hydrochloride, tar, 1,2-trichloroethane, and N,N'-dimethylformamide. The actual content of 4,1',6'-trichlorosucrose is 1-10 wt%.

[0011] The sucrose acylation-chlorination reaction solution is a material solution obtained by selectively acetylating the 6-position hydroxyl group of sucrose, but directly performing selective chlorination of the 4,1',6'-position hydroxyl groups without purifying sucrose-6-acetate. The method for selectively acetylating the 6-position hydroxyl group of sucrose is the dibutyltin oxide method, and the method for selectively chlorinating the 4,1',6'-position hydroxyl groups is the Vilsmeier reagent method. The specific steps include: (1) Adding the catalyst 1,3-bis(acetyloxy)-1,1,3,3-tetrabutyldistannoxane (DSDA) to the N,N-dimethylformamide solution of sucrose, and carrying out vacuum distillation at 80-90 °C to continuously remove the water generated by the reaction until no liquid can be distilled out. A certain amount of N,N'-dimethylformamide is added, cooled to -5~5 °C, acetic anhydride is dropped, stirred for 3-6 h, and then quenched with deionized water. Finally, cyclohexane is used to extract and recover DSDA in the reaction solution, and acetic acid and water are removed by vacuum distillation at 60-80 °C, and N,N'-dimethylformamide is added to prepare a sucrose acylation synthesis solution. (2) At -5~5 °C, the sucrose acylation synthesis solution is dropped into a mixed solution of 1,1,2-trichloroethane and thionyl chloride, heated to 20-35 °C and stirred for 0.5-1 h, heated to 70-85 °C at 1-2 °C / min and reacted for 1-1.5 h, then heated to 90-100 °C at 0.5-1 °C / min and reacted for 1-1.5 h, and finally heated to 105-115 °C at 0.1-0.3 °C / min for reflux reaction for 1-2 h; to obtain a sucrose acylation-chlorination reaction solution.

[0012] The "filtering to remove residues" in the first step means filtering under suction to remove solid particles such as carbon residues and salts.

[0013] The "concentrating to remove solvents" in the first step means removing more than 90 wt% of organic solvents such as 1,1,2-trichloroethane and N,N'-dimethylformamide by vacuum distillation at 50 - 90 °C.

[0014] Preferably, the first organic solvent in the first step is at least one of butyl acetate, amyl acetate, isoamyl acetate, butyl propionate, and amyl propionate.

[0015] Preferably, the mass ratio of the first organic solvent to the aqueous solution in the first step is 0.2:1 - 2:1.

[0016] Preferably, the second organic solvent in the first step is at least one of ethyl acetate, propyl acetate, isopropyl acetate, and ethyl propionate.

[0017] Preferably, the mass ratio of the second organic solvent to the aqueous solution in the first step is 0.2:1 - 2:1.

[0018] The "decolorizing and concentrating" in the first step means adding activated carbon with a mass 1 / 5 - 1 / 20 times that of the second organic solvent phase for decolorization, filtering the activated carbon, and performing vacuum distillation at 0.07 - 0.1 MPa and 30 - 70 °C for 30 - 240 min to remove the second organic solvent.

[0019] Preferably, the third organic solvent in the second step is at least one of methanol and ethanol.

[0020] Preferably, the mass ratio of the third organic solvent to the crude sucralose product in the second step is 4:1 - 20:1.

[0021] Preferably, the fourth organic solvent in the second step is at least one of oleic acid, linoleic acid, α-linolenic acid, isovaleric acid, n-hexanoic acid, n-heptanoic acid, n-decanoic acid, n-propyl ether, and isopropyl ether.

[0022] Preferably, the mass ratio of the fourth organic solvent to the third organic solvent in the second step is 1:1 - 20:1.

[0023] Preferably, the mass ratio of the sucralose crystal seeds to the third organic solvent in the second step is 0.0008:1 - 0.05:1.

[0024] Preferably, the stirring and crystallization time in the second step is 3 - 24 h.

[0025] Preferably, the crystallization temperature in the second step is any constant temperature within the range of 10 - 40 °C.

[0026] Preferably, the mass ratio of sucralose solid to pure water in the second step is 4:1 to 20:1.

[0027] Preferably, the temperature for recrystallization from pure water in the second step is reduced from 50 - 60 °C to 0 - 10 °C.

[0028] Preferably, the drying temperature in the second step is 40 - 60 °C, the pressure is -0.1 to 0.04 MPa, and the drying time is 12 - 24 h.

[0029] It should be noted that the actual content of sucralose in the sucralose mixture liquid described in the first step is 1 - 10 wt%, and the purity shown by HPLC - ELSD is 30 - 40%. The actual purity of the qualified sucralose product described in the second step exceeds 98%, and the purity shown by HPLC - ELSD is greater than 99.4%.

[0030] Compared with the prior art, the advantages and outstanding effects of the present invention are as follows:

[0031] (1) During the purification of sucralose in the present invention, it has the characteristics of fast crystallization rate, high separation selectivity and yield. At the same time, the "solvent - anti - solvent" crystallization is carried out at a constant room temperature (the error does not exceed ±1 °C), greatly reducing the energy consumption during the crystallization process, and the conditions are mild, the operation is convenient, and it is suitable for industrial application.

[0032] (2) The present invention combines the chlorination alkali neutralization and alkali - catalyzed alcoholysis in the sucralose production process into one, greatly simplifying the production steps of sucralose, directly shortening the three - step reaction of the traditional process to a two - step reaction, and shortening the purification process in the production process, having excellent industrial value. BRIEF DESCRIPTION OF THE DRAWINGS

[0033] Figure 1 is the process route diagram of the sucralose production process of the present invention;

[0034] Figure 2 is the HPLC - ELSD chromatogram before and after the antisolvent crystallization of sucralose in Example 1, a - dichlorosucrose (1’,6’ - dichloro - 1’,6’ - dideoxysucrose, 1,6 - dichloro - 1,6 - dideoxy - D - fructose); b - sucralose; c - sucralose (1’,6,6’ - trichloro - 1’,6,6’ - dideoxysucrose); d - sucralose - 6 - acetate;

[0035] Figure 3 is the FT - IR diagram before and after the antisolvent crystallization of sucralose in Example 1;

[0036] Figure 4 is the XRD diagram before and after the antisolvent crystallization of sucralose in Example 1;

[0037] Figure 5 SEM image after fractional crystallization of sucralose in Example 1. Detailed implementation mode

[0038] The present invention will be described in detail below in conjunction with specific embodiments.

[0039] A fractional crystallization process of sucralose includes the following steps:

[0040] 1) Enrich sucralose in the organic phase by stepwise extraction of the aqueous solution of crude sucralose product, decolorize and concentrate to obtain the crude sucralose product; the stepwise extraction uses a first organic solvent and a second organic solvent;

[0041] 2) Stepwise add a third organic solvent equivalent to 4-20 times the mass of the crude sucralose product and a fourth organic solvent equivalent to 1-20 times the mass of the third organic solvent to completely dissolve the crude sucralose product; add a small amount of seeds thereto and stir to obtain sucralose crystals;

[0042] 3) Stepwise add a third organic solvent equivalent to 4-20 times the mass of the sucralose crystals and a fourth organic solvent equivalent to 1-20 times the mass of the third organic solvent to completely dissolve the sucralose crystals; add a small amount of seeds thereto and stir to obtain sucralose solid powder;

[0043] 4) Dissolve the sucralose solid powder in pure water with a mass 4-20 times that of the powder, cool for recrystallization, and dry the crystallization product to obtain the sucralose product.

[0044] Further, the aqueous solution of the crude sucralose product is a mixed solution of sucralose obtained by subjecting a sucrose acylation-chlorination reaction solution to low-temperature catalytic treatment with high-concentration sodium hydroxide and quenching with hydrochloric acid, and then respectively subjected to solid particle removal treatment and more than 90% organic solvent removal by vacuum distillation and dissolved in pure water.

[0045] Further, the stepwise extraction includes extraction with a first organic solvent and a second organic solvent. The first organic solvent includes butyl acetate, amyl acetate, isoamyl acetate, butyl propionate or pentyl propionate; the second organic solvent includes ethyl acetate, propyl acetate, isopropyl acetate or ethyl propionate.

[0046] Further, the "decolorize and concentrate" means decolorize with activated carbon, filter to remove the activated carbon, and vacuum distill for 30-240 min at 0.07-0.1 MPa and 30-70 °C to remove the organic solvent.

[0047] Further, the third organic solvent includes methanol or ethanol; the fourth organic solvent includes oleic acid, linoleic acid, α-linolenic acid, isovaleric acid, n-caproic acid, n-heptanoic acid, n-decanoic acid, n-propyl ether or isopropyl ether.

[0048] Further, the cooling and recrystallization is carried out by cooling from a temperature of 50-60 °C to 0-10 °C.

[0049] Example 1

[0050] Take 10 g of an aqueous solution of crude sucralose product with a content of 7.5 wt%, add 10 g of butyl acetate for extraction, and separate the aqueous phase and the butyl acetate phase. Then add 10 g of ethyl acetate to the aqueous phase for extraction, and separate the aqueous phase and the ethyl acetate phase. Add 2 g of activated carbon to the organic phase for decolorization, and after filtration, completely evaporate the ethyl acetate at 50 °C and 0.1 MPa to obtain the crude sucralose product. Dissolve the crude sucralose product with 3 g of methanol. After complete dissolution, add 3 g of oleic acid and 0.003 g of high-purity sucralose solid and stir at 30 °C and 1000 r / min. White crystals will continuously precipitate in the system. After 12 h, stop stirring, take out all the solid-liquid, and perform centrifugal separation. Repeat the "methanol-oleic acid" crystallization experiment once on the obtained solid. Finally, dissolve the obtained solid in pure water at 60 °C and remove a small amount of suspended oleic acid, and slowly cool down to 10 °C to obtain sucralose crystals. Dry the crystals in vacuo at 50 °C until completely dry. Through weighing and HPLC-ELSD analysis, the relative content of sucralose is 99.25 wt%.

[0051] Example 2

[0052] Take 10 g of an aqueous solution of crude sucralose product with a content of 7.5 wt%, add 12 g of butyl acetate for extraction, and separate the aqueous phase and the butyl acetate phase. Then add 12 g of ethyl acetate to the aqueous phase for extraction, and separate the aqueous phase and the ethyl acetate phase. Add 2 g of activated carbon to the organic phase for decolorization, and after filtration, completely evaporate the ethyl acetate at 50 °C and 0.1 MPa to obtain the crude sucralose product. Dissolve the crude sucralose product with 2.5 g of methanol. After complete dissolution, add 2.5 g of oleic acid and 0.0025 g of high-purity sucralose solid and stir at 30 °C and 1000 r / min. White crystals will continuously precipitate in the system. After 12 h, stop stirring, take out all the solid-liquid, and perform centrifugal separation. Repeat the "methanol-oleic acid" crystallization experiment once on the obtained solid. Finally, dissolve the obtained solid in pure water at 60 °C and remove a small amount of suspended oleic acid, and slowly cool down to 10 °C to obtain sucralose crystals. Dry the crystals in vacuo at 50 °C until completely dry. Through weighing and HPLC-ELSD analysis, the relative content of sucralose is 99.51 wt%.

[0053] Example 3

[0054] Take 10 g of an aqueous solution of sucralose crude product with a content of 7.5 wt%, add 10 g of butyl propionate for extraction, and separate the aqueous phase and the butyl propionate phase. Then add 10 g of propyl acetate to the aqueous phase for extraction, and separate the aqueous phase and the propyl acetate phase. Add 2 g of activated carbon to the organic phase for decolorization. After filtration, completely evaporate the propyl acetate at 50 °C and 0.1 MPa to obtain the sucralose crude product. Dissolve the sucralose crude product with 3 g of ethanol. After complete dissolution, add 3 g of isopropyl ether and 0.003 g of high-purity sucralose solid, and stir at 30 °C and 1000 r / min. White crystals will continuously precipitate in the system. After 12 h, stop stirring, take out all the solid-liquid, perform centrifugal separation, and repeat the "ethanol-isopropyl ether" crystallization experiment once on the obtained solid. Finally, dissolve the obtained solid in pure water at 60 °C, slowly cool it to 10 °C to obtain sucralose crystals. Dry the crystals in vacuo at 50 °C until completely dry. Through weighing and HPLC-ELSD analysis, the relative content of sucralose is 99.06 wt%.

[0055] Example 4

[0056] Take 10 g of an aqueous solution of sucralose crude product with a content of 7.5 wt%, add 12 g of amyl acetate for extraction, and separate the aqueous phase and the amyl acetate phase. Then add 12 g of isopropyl acetate to the aqueous phase for extraction, and separate the aqueous phase and the isopropyl acetate phase. Add 2 g of activated carbon to the organic phase for decolorization. After filtration, completely evaporate the isopropyl acetate at 50 °C and 0.1 MPa to obtain the sucralose crude product. Dissolve the sucralose crude product with 2.5 g of ethanol. After complete dissolution, add 2.5 g of isovaleric acid and 0.0025 g of high-purity sucralose solid, and stir at 30 °C and 1000 r / min. White crystals will continuously precipitate in the system. After 12 h, stop stirring, take out all the solid-liquid, perform centrifugal separation, and repeat the "ethanol-isovaleric acid" crystallization experiment once on the obtained solid. Finally, dissolve the obtained solid in pure water at 60 °C, slowly cool it to 10 °C to obtain sucralose crystals. Dry the crystals in vacuo at 50 °C until completely dry. Through weighing and HPLC-ELSD analysis, the relative content of sucralose is 99.35 wt%.

[0057] The above detailed description of the production process of a kind of sucralose with reference to the examples is illustrative rather than restrictive. Several examples can be listed within the defined scope. Therefore, changes and modifications without departing from the general concept of the present invention shall fall within the protection scope of the present invention.

Claims

1. A fractional crystallization process of sucralose, characterized in that, It includes the following steps: 1) Enrich sucralose in the organic phase by stepwise extraction of the aqueous solution of crude sucralose products, decolorize and concentrate to obtain crude sucralose products; the stepwise extraction uses a first organic solvent and a second organic solvent; 2) Stepwise add a third organic solvent equivalent to 4 to 20 times the mass of the crude sucralose product and a fourth organic solvent equivalent to 1 to 20 times the mass of the third organic solvent to completely dissolve the crude sucralose product; add a small amount of seeds thereto and stir to obtain sucralose crystals; 3) Stepwise add a third organic solvent equivalent to 4 to 20 times the mass of the sucralose crystals and a fourth organic solvent equivalent to 1 to 20 times the mass of the third organic solvent to completely dissolve the sucralose crystals; add a small amount of seeds thereto and stir to obtain sucralose solid powder; 4) Dissolve the sucralose solid powder in pure water with a mass 4 to 20 times that of the powder, cool for recrystallization, and dry the crystallization product to obtain sucralose products; The stepwise extraction includes extraction with a first organic solvent and a second organic solvent, the first organic solvent includes butyl acetate, amyl acetate or butyl propionate; the second organic solvent includes ethyl acetate, propyl acetate or ethyl propionate; The third organic solvent includes methanol or ethanol; the fourth organic solvent includes oleic acid, isovaleric acid, n-hexanoic acid, n-heptanoic acid, n-decanoic acid or isopropyl ether.

2. The fractional crystallization process of sucralose according to claim 1, characterized in that, The aqueous solution of the crude sucralose product is a mixed solution of sucralose obtained by low-temperature catalytic treatment of a sucrose acylation-chlorination reaction solution with high-concentration sodium hydroxide and quenched with hydrochloric acid, and then is a solution dissolved in pure water after respectively removing solid particles and removing more than 90% of organic solvents by vacuum distillation.

3. The fractional crystallization process of sucralose according to claim 1, characterized in that, The "decolorize and concentrate" means decolorize with activated carbon, filter to remove the activated carbon, and remove organic solvents by vacuum distillation at 0.07 to 0.1 MPa and 30 to 70 °C for 30 to 240 min.

4. The fractional crystallization process of sucralose according to claim 1, characterized in that, The crystallization temperature in steps 2) and 3) is any constant temperature in the range of 10 to 40 °C, with an error not exceeding ±1 °C.

5. The fractional crystallization process of sucralose according to claim 1, characterized in that, The cooling for recrystallization is from a temperature of 50 to 60 °C to 0 to 10 °C.

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