Method for preparing sucralose crude product and application

Abstract

The invention discloses a method for preparing a sucralose crude product and application, and belongs to the technical field of sucralose production.The method comprises the steps that a mixed solution of ethyl acetate and butyl acetate with the volume ratio being 1: (0.5-3) is used for extracting a raw material solution, and the sucralose crude product is obtained; the application refers to application of a mixed solution of ethyl acetate and butyl acetate in preparation of a sucralose crude product, and the volume ratio of ethyl acetate to butyl acetate in the mixed solution is 1: (0.5-3). According to the method disclosed by the invention, substances with strong polarity in the raw material solution are not extracted out through the extraction of the mixed solution of the ethyl acetate and the butyl acetate, the impurity content in the subsequent steps is reduced, the substances can be recycled in a system, the cost is reduced, the sucralose is enriched, the sucralose can be massively crystallized in the mixed solution of the ethyl acetate and the butyl acetate, and the purity of the sucralose is improved. The loss of the sucralose is avoided, and the overall yield of the sucralose is greatly improved. Compared with the prior art, the method has the advantages of less impurity generation, high yield and lower cost.

Description

Technical Field

[0001] The invention belongs to the technical field of sucralose production, and particularly relates to a method for preparing crude sucralose and application thereof. Background Art

[0002] Sucralose is an artificial sweetener made from sucrose, which is 400-800 times sweeter than sucrose. It has a pure taste and does not participate in human metabolism. It is a "zero-calorie" sugar that can be used by diabetics, patients with cardiovascular and cerebrovascular diseases and the elderly. It also has the characteristics of good stability and high safety, and is widely used in many fields such as food, beverages, daily chemicals and medicine.

[0003] At present, the production process of sucralose mainly includes the following five steps: (1) esterification reaction (2) chlorination reaction (3) purification of sucralose-6-acetate (4) alcoholysis reaction (5) separation and purification. In the alcoholysis process using sucralose-6-acetate as raw material, high-purity (more than 99%) sucralose-6-acetate is required, because too much impurities will seriously affect the subsequent purification of sucralose and reduce the yield. Chinese patents CN104004032A, CN112805291A, CN101012250A and CN112771059A all use high-purity sucralose-6-acetate as raw material to prepare sucralose through alcoholysis reaction. However, sucralose-6-acetate is lost greatly during the purification process, which leads to a relatively low yield of sucralose.

[0004] Chinese patents CN115956082A and CN116075518B use an aqueous solution containing sucralose-6-acetate as a raw material, extract with ethyl acetate, remove some impurities from the obtained ester phase containing sucralose-6-acetate, and then use a sodium hydroxide / water system for alkaline hydrolysis and purification to obtain sucralose. Although the patent uses a neutralized solution containing sucralose-6-acetate as a raw material and has a molar yield of 103.7-105.1%, some impurities still remain, affecting the yield and quality. Summary of the invention

[0005] In view of the problems existing in the prior art, the present invention provides a method for preparing crude sucralose, which converts sucralose-6-acetate and impurities (sucralose diester and tetrachlorosucrose-6-acetate) in a raw material liquid into sucralose, thereby significantly improving the raw material conversion rate and the yield of sucralose.

[0006] To achieve the above purpose, the technical solution adopted by the present invention is as follows:

[0007] In a first aspect, the present invention provides use of a mixture of ethyl acetate and butyl acetate in the preparation of crude sucralose.

[0008] In some embodiments, the volume ratio of ethyl acetate to butyl acetate in the mixed solution is 1:0.5-3; preferably 1:0.5-3, 1:0.5-2, 1:0.8-1.2, 1:0.8-1; 1:1-1.2 or 1:1.

[0009] The mixed solution of ethyl acetate and butyl acetate in the present invention is used for extraction so that highly polar substances in the raw material solution are not extracted, thereby reducing the impurity content in the subsequent steps, and the method can be circulated in the system to reduce costs and enrich sucralose. Moreover, sucralose can be crystallized in a large amount in the mixed solution of ethyl acetate and butyl acetate, thereby avoiding the loss of sucralose and greatly improving the overall yield of sucralose.

[0010] In a second aspect, the present invention provides a method for preparing crude sucralose, comprising the following steps:

[0011] (1) extracting the raw material liquid with a mixed solution of ethyl acetate and butyl acetate to obtain a first ester phase and a first aqueous phase; the raw material liquid is an aqueous solution including sucralose-6-acetate, sucralose diester and tetrachlorosucrose-6-acetate;

[0012] (2) concentrating the first ester phase in step (1) to dryness, adding water to dissolve, and concentrating to obtain a sucralose-6-acetate aqueous solution;

[0013] (3) subjecting the aqueous solution of sucralose-6-acetate described in step (2) to alkaline hydrolysis, neutralization, and filtering to obtain a second aqueous phase;

[0014] (4) extracting the second aqueous phase in step (3) with a mixture of ethyl acetate and butyl acetate to obtain a second ester phase and a third aqueous phase;

[0015] (5) washing the second ester phase in step (4) with water to obtain a third ester phase and a fourth aqueous phase;

[0016] (6) After the third ester phase in step (5) is concentrated and dried, a mixture of ethyl acetate and butyl acetate is added and mixed to obtain a concentrate, and then a mixture of ethyl acetate and butyl acetate is added to obtain a fourth ester phase;

[0017] (7) crystallizing the fourth ester phase in step (6) to obtain crude sucralose and a fifth ester phase;

[0018] (8) washing the fifth ester phase in step (7) with water to obtain a sixth ester phase and a fifth aqueous phase;

[0019] (9) Repeat steps (1) to (8) at least twice, and concentrate the sixth ester phase in step (8) to obtain crude sucralose.

[0020] In some embodiments, the volume ratio of the raw material solution to the mixed solution in step (1) is 10:1-5; preferably 10:2-4; more preferably 10:2.5-3.5; and more preferably 10:3.

[0021] In some embodiments, the raw material solution in step (1) includes sucralose-6-acetate, sucralose diester, tetrachlorosucrose-6-acetate, NH4Cl, other organic impurities and water.

[0022] In some embodiments, the content of sucralose-6-acetate is 40-70 g / L; preferably 50-60 g / L; more preferably 53-55 g / L; more preferably 53.5-54 g / L; more preferably 53.8 g / L.

[0023] In some embodiments, the content of sucralose diester is 2-10 g / L; preferably 3-8 g / L; more preferably 3.5-5 g / L; more preferably 4-4.5 g / L; more preferably 4.2 g / L.

[0024] In some embodiments, the content of sucralose-6-acetate is 2-10 g / L; preferably 3-8 g / L; more preferably 5-6 g / L; more preferably 5.2-5.6 g / L; more preferably 5.4 g / L.

[0025] In some embodiments, the content of NH4Cl is 70-90 g / L; preferably 80-87 g / L; further preferably 83-84 g / L; further preferably 83.5-84 g / L; further preferably 83.7 g / L.

[0026] In some embodiments, the content of other organic impurities is 20-50 g / L; preferably 35-37 g / L; more preferably 31-33 g / L; more preferably 31.5-32.3 g / L; more preferably 31.9 g / L.

[0027] In some embodiments, the water content is 70-90 wt %; preferably 80-89 wt %; more preferably 83-87 wt %; more preferably 84.5-85 wt %; more preferably 84.8 wt %.

[0028] In some embodiments, the extraction conditions in steps (1) and (4) are extraction at 55-65°C for 10-20 min, preferably extraction at 60°C for 15 min.

[0029] In some embodiments, the number of extractions in steps (1) and (4) is at least 2 times, preferably 3-15 times; more preferably 3-10 times; more preferably 3-8 times; more preferably 5 times.

[0030] In some embodiments, the concentration in step (2) is concentrated to 50-70% of the volume of the original solvent; preferably 55-65%; more preferably 58-62%; and more preferably 60%.

[0031] In some embodiments, the alkaline hydrolysis reaction in step (3) is: adding alkali solution at -4 to 4°C, reacting for 4-6 hours, the concentration of the alkali solution is 25-45wt%, preferably 30-40wt%; more preferably 33-37wt%; more preferably 35wt%; the pH of the reaction system of the alkaline hydrolysis reaction is 11-13; preferably 11.5-12.5; more preferably 11.8-12.2; more preferably 12; the alkali in the alkali solution is potassium hydroxide and / or sodium hydroxide; preferably potassium hydroxide.

[0032] In some embodiments, the neutralization in step (3) is: adding acid to adjust the pH of the reaction system to 6.5-7.5; preferably 6.8-7.2; more preferably 7; the acid is dilute sulfuric acid, and the mass concentration of the sulfuric acid is 20-40wt%; preferably 25-35wt%; more preferably 28-32wt%; more preferably 30wt%.

[0033] In some embodiments, the number of water washing in step (5) is at least 2 times, preferably 3-15 times; more preferably 3-10 times; more preferably 3-8 times; more preferably 5 times.

[0034] In some embodiments, the sugar content Bx in the fourth ester phase in step (6) is 35-50%; preferably 40-50%; more preferably 43-47%; and more preferably 45%.

[0035] In some embodiments, the crystallization in step (7) is carried out at 40-50°C for 12-36 hours; preferably at 45°C for 24 hours.

[0036] In some embodiments, the number of water washings in step (8) is at least 2 times, preferably 3-15 times; more preferably 3-10 times; more preferably 3-8 times; more preferably 5 times.

[0037] In some embodiments, the extraction in step (4) is divided into 5 times, wherein the ester phases obtained from the 1st to 2nd extractions are combined as the second ester phase; and the ester phases obtained from the 3rd to 5th extractions successively replace the mixed solution of ethyl acetate and butyl acetate used in the 1st to 3rd extractions of the second aqueous phase in step (3).

[0038] In some embodiments, the number of water washings in step (5) is 5 times, and the aqueous phase obtained from the first water washing is used as the fourth aqueous phase; the fourth aqueous phase replaces the water in step (2); the aqueous phases obtained from the second to fifth water washings are used sequentially for the first to fourth water washings of the second ester phase in step (5), and the ester phases obtained from the five water washings are combined as the third ester phase.

[0039] In some embodiments, the fifth aqueous phase in step (8) replaces the water in step (2).

[0040] Compared with the prior art, the present invention has the following beneficial effects:

[0041] (1) The present invention provides a method for preparing crude sucralose. First, the present invention adopts a dual system of ethyl acetate and butyl acetate-water, which can realize mutual extraction and impurity removal between the dual systems, enrich sucralose, so that sucralose can be crystallized in ethyl acetate and butyl acetate in large quantities, avoiding the loss of sucralose and greatly improving the overall yield of sucralose. Second, the present invention performs alkaline hydrolysis under a potassium hydroxide-water system, and sucralose-6-acetate, sucralose diester and tetrachlorosucrose-6-acetate are all alkaline-hydrolyzed in a strong alkaline aqueous solution to generate corresponding sucralose and tetrachlorosucrose. Tetrachlorosucrose can continue to be dechlorinated in a strong alkaline aqueous solution to form sucralose, so that sucralose-6-acetate and impurities (sucralose diester and tetrachlorosucrose-6-acetate) in the raw material liquid are converted into sucralose, thereby significantly improving the raw material conversion rate and the yield of sucralose. Thirdly, the present invention adopts dilute sulfuric acid for neutralization, so that potassium salt is produced in the reaction system, which can be used as fertilizer for subsequent development, thereby developing by-products and increasing profits.

[0042] (2) Compared with the prior art, the present invention produces less impurities, has a higher yield, and has lower cost. DETAILED DESCRIPTION

[0043] The present invention is described below through specific embodiments to make the technical solution of the present invention easier to understand and grasp, but the present invention is not limited thereto, and the described embodiments are only a part of the embodiments of the present invention, rather than all of the embodiments.

[0044] The endpoints and any value of the scope disclosed in this article are not limited to the accurate scope or value, and these scopes or values ​​should be understood to include values ​​close to these scopes or values. For numerical ranges, between the endpoint values ​​of each scope, between the endpoint values ​​of each scope and a separate point value, and between separate point values, one or more new numerical ranges can be combined with each other, and these numerical ranges should be considered as specifically disclosed in this article. Unless the context clearly indicates otherwise, the singular form "one", "a kind of" and "described" as used herein include singular and plural indicators. The numerical range described by the endpoint is included in all numerical values ​​and fractions within the corresponding range, as well as the described endpoint.

[0045] The "concentrated to dryness" mentioned in the present invention refers to vacuum concentration to dryness. Those skilled in the art may adopt conventional temperature and pressure, such as 80°C, -0.08MPa or 70°C, -0.1Mpa.

[0046] The "concentration" mentioned in the present invention is vacuum concentration, and those skilled in the art may adopt conventional temperature and pressure, such as 80°C, -0.08MPa or 70°C, -0.1Mpa.

[0047] Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without creative work should belong to the scope of protection of the present invention. The experimental methods described in the following embodiments are conventional methods unless otherwise specified. The reagents and materials, unless otherwise specified, can be obtained from commercial channels. The following reagent source information is illustrative and should not be used to limit the present invention.

[0048] In this embodiment, the raw material liquid is recorded as the first aqueous solution.

[0049] Example 1

[0050] (1) Extraction step: 1000 mL of the first aqueous solution was placed in a 2 L eggplant-shaped bottle, 300 mL of a mixture of ethyl acetate and butyl acetate (v / v=1:1) was added, and the mixture was stirred and extracted at 60° C. for 15 min. The phases were separated to obtain an organic phase and an aqueous phase. The aqueous phase was subjected to the above extraction step for 5 times. After the extraction was completed, the ester phases were combined as the first ester phase. The aqueous phase obtained from the last extraction was the first aqueous phase (the content of sucralose-6-acetate was 0.09 g / L).

[0051] The composition of the first aqueous solution is shown in Table 1.

[0052] Table 1 Composition of the first aqueous solution

[0053] Components content Sucralose-6-acetate 53.8g / L Sucralose diester 4.2g / L Sucralose-6-acetate 5.4g / L <![CDATA[NH4Cl]]> 83.7g / L Other organic impurities 31.9g / L water 84.8％

[0054] (2) Concentration and drying step: The first ester phase was concentrated and dried at 80° C. and −0.08 MPa, water was added to the obtained first ester phase concentrate to make 1000 mL, and the concentrate was concentrated to 600 mL at 80° C. and −0.08 MPa to obtain a sucralose-6-acetate aqueous solution (ethyl acetate content: 0.43 g / L), which was then transferred to a 1000 mL three-necked flask.

[0055] (3) Alkaline hydrolysis step: The obtained sucralose-6-acetate aqueous solution was cooled to 0°C, and then a 35 wt% potassium hydroxide aqueous solution was added dropwise to mix evenly, and alkaline hydrolysis was performed at 0°C for 5 h. During the alkaline hydrolysis, the pH value of the system was maintained at 12.0. After the alkaline hydrolysis was completed, 30 wt% dilute sulfuric acid was added dropwise to neutralize to pH = 7, and the solution was heated to 60°C for hot filtration to obtain a second aqueous phase (650 mL, sucralose-6-acetate content of 0.04 g / L).

[0056] (4) Separation step: add 1.3L of a mixture of ethyl acetate and butyl acetate (v / v=1:1) to the second aqueous phase, stir and extract at 60°C for 15min, repeat the above extraction operation for the obtained aqueous phase, extract 5 times in total, combine the ester phases obtained from the 1st and 2nd extractions as the second ester phase (2.8L), and the ester phases obtained from the 3rd to 5th extractions with a mixture of ethyl acetate and butyl acetate are successively used as the 1st to 3rd extractions with a mixture of ethyl acetate and butyl acetate of the second aqueous phase in the preparation process of the next batch of crude sucralose. Add 550mL of water to the second ester phase for water washing, wash 5 times, the aqueous phase obtained from the first water washing is the fourth aqueous phase, the fourth aqueous phase is used in step (2) to replace water and mix with the first ester phase concentrate; the aqueous phase obtained from the 2nd to 5th water washings are successively used as the 1st to 4th water washings of the second ester phase in the preparation process of the next batch of crude sucralose, and the ester phase obtained after the washing is the third ester phase. The third ester phase was concentrated and dried at 70° C. and −0.1 MPa (gauge pressure). During the concentration and drying process, a mixed solution of ethyl acetate and butyl acetate was added (the number of additions was 3 times, 300 mL was added each time) for dehydration to ensure that the water was completely removed. A mixed solution of ethyl acetate and butyl acetate was added to the obtained third ester phase concentrate to adjust the sugar content Bx to 45%, thereby obtaining a fourth ester phase.

[0057] (5) Crystallization step: crystallize the fourth ester phase at 45° C. for 24 h, filter and obtain 420 mL of crude sucralose and the fifth ester phase (after equilibration four times); wash the fifth ester phase with water five times (each time with 210 mL of water), the ester phase after washing with water is the sixth ester phase (sucralose content 0.03 g / L), concentrate and dry the sixth ester phase to obtain a mixed solution of recovered ethyl acetate and butyl acetate and a sugar residue; combine the aqueous phases as the fifth aqueous phase, and use the fifth aqueous phase in step (2) to replace water and mix with the first ester phase concentrate.

[0058] (6) According to the operation of steps (1) to (5) (recorded as recycling 0 times), the fourth aqueous phase and the fifth aqueous phase were recycled 15 times, wherein "adding water to 1000 mL of the obtained first ester phase concentrate" in step (1) was modified to "mixing the obtained first ester phase, the fourth aqueous phase and the fifth aqueous phase"; in step (4), the 1st to 3rd extractions of the second aqueous phase with a mixed solution of ethyl acetate and butyl acetate were carried out using the ester phase obtained by the 3rd to 5th extractions of the second aqueous phase with a mixed solution of ethyl acetate and butyl acetate in the preparation process of the previous batch of crude sucralose, and the 4th to 5th extractions of the second aqueous phase with a mixed solution of ethyl acetate and butyl acetate were carried out using a mixed solution of pure ethyl acetate and butyl acetate; the 1st to 4th water washings of the second ester phase were carried out using the aqueous phase obtained by the 2nd to 5th water washings of the second ester phase in the preparation process of the previous batch of crude sucralose, and the 5th water washing of the second ester phase was carried out using pure water; the purity and yield data of the obtained crude sucralose are shown in Table 2.

[0059] Table 2 Purity and yield of crude sucralose

[0060]

[0061] Note: Yield = mass of sucralose / mass of sucralose-6-acetate completely converted to sucralose × 100%.

[0062] Example 2

[0063] The difference between this embodiment and embodiment 1 is that the components of the mixed solution of ethyl acetate and butyl acetate and the first aqueous solution in step (1) are different, and the remaining steps are the same.

[0064] (1) Extraction step: 1000 mL of the first aqueous solution was placed in a 2 L eggplant-shaped bottle, 300 mL of a mixture of ethyl acetate and butyl acetate (v / v=1:0.5) was added, and the mixture was stirred and extracted at 60° C. for 15 min. The phases were separated to obtain an organic phase and an aqueous phase. The aqueous phase was subjected to the above extraction step for 5 times. After the extraction was completed, the ester phases were combined as the first ester phase. The aqueous phase obtained from the last extraction was the first aqueous phase (the content of sucralose-6-acetate was 0.08 g / L).

[0065] The composition of the first aqueous solution is shown in Table 3.

[0066] Table 3 Composition of the first aqueous solution

[0067] Components content Sucralose-6-acetate 53.5g / L Sucralose diester 4.1g / L Sucralose-6-acetate 5.3g / L NH4Cl 83.7g / L Other organic impurities 31.9g / L water 84.8wt%

[0068] (2) Concentration and drying step: The first ester phase was concentrated and dried at 80° C. and −0.08 MPa, water was added to the obtained first ester phase concentrate to make 1000 mL, and the concentrate was concentrated to 600 mL at 80° C. and −0.08 MPa to obtain a sucralose-6-acetate aqueous solution (ethyl acetate content: 0.39 g / L), which was then transferred to a 1000 mL three-necked flask.

[0069] (3) Alkaline hydrolysis step: The obtained sucralose-6-acetate aqueous solution was cooled to 0°C, and then a 35 wt% potassium hydroxide aqueous solution was added dropwise to mix evenly, and alkaline hydrolysis was performed at 0°C for 5 h. During the alkaline hydrolysis, the pH value of the system was maintained at 12.0. After the alkaline hydrolysis was completed, 30 wt% dilute sulfuric acid was added dropwise to neutralize to pH = 7, and the solution was heated to 60°C for hot filtration to obtain a second aqueous phase (660 mL, sucralose-6-acetate content of 0.03 g / L).

[0070] (4) Separation step: add 1.3L of a mixture of ethyl acetate and butyl acetate (v / v=1:0.5) to the second aqueous phase, stir and extract at 60°C for 15min, repeat the above extraction operation for the obtained aqueous phase, extract 5 times in total, combine the ester phases obtained from the 1st and 2nd extractions as the second ester phase (2.8L), and the ester phases obtained from the 3rd to 5th extractions with the mixture of ethyl acetate and butyl acetate are successively used as the 1st to 3rd extractions with the mixture of ethyl acetate and butyl acetate of the second aqueous phase in the preparation process of the next batch of crude sucralose. Add 550mL of water to the second ester phase for water washing, wash 5 times, the aqueous phase obtained from the first water washing is the fourth aqueous phase, the fourth aqueous phase is used in step (2) to replace water and mix with the first ester phase concentrate; the aqueous phase obtained from the 2nd to 5th water washings are successively used as the 1st to 4th water washings of the second ester phase in the preparation process of the next batch of crude sucralose, and the ester phase obtained after the washing is the third ester phase. The third ester phase was concentrated and dried at 70° C. and −0.1 MPa (gauge pressure). During the concentration and drying process, a mixed solution of ethyl acetate and butyl acetate was added (the number of additions was 3 times, 300 mL was added each time) for dehydration to ensure that the water was completely removed. A mixed solution of ethyl acetate and butyl acetate was added to the obtained third ester phase concentrate to adjust the sugar content Bx to 45%, thereby obtaining a fourth ester phase.

[0071] (5) Crystallization step: crystallize the fourth ester phase at 45° C. for 24 h, filter and obtain crude sucralose and 410 mL of the fifth ester phase (after equilibration four times); wash the fifth ester phase with water five times (each time with 200 mL of water), the ester phase after washing with water is the sixth ester phase (sucralose content 0.04 g / L), concentrate and dry the sixth ester phase to obtain a mixed solution of recovered ethyl acetate and butyl acetate and a sugar residue; combine the aqueous phases as the fifth aqueous phase, and use the fifth aqueous phase in step (2) to replace water and mix with the first ester phase concentrate.

[0072] (6) According to the operation of steps (1) to (5) (recorded as recycling 0 times), the fourth aqueous phase and the fifth aqueous phase were recycled 15 times, wherein "adding water to 1000 mL of the obtained first ester phase concentrate" in step (1) was modified to "mixing the obtained first ester phase, the fourth aqueous phase and the fifth aqueous phase"; in step (4), the 1st to 3rd extractions of the second aqueous phase with a mixed solution of ethyl acetate and butyl acetate were carried out using the ester phase obtained by the 3rd to 5th extractions of the second aqueous phase with a mixed solution of ethyl acetate and butyl acetate in the preparation process of the previous batch of crude sucralose, and the 4th to 5th extractions of the second aqueous phase with a mixed solution of ethyl acetate and butyl acetate were carried out using a mixed solution of pure ethyl acetate and butyl acetate; the 1st to 4th water washings of the second ester phase were carried out using the aqueous phase obtained by the 2nd to 5th water washings of the second ester phase in the preparation process of the previous batch of crude sucralose, and the 5th water washing of the second ester phase was carried out using pure water; the purity and yield data of the obtained crude sucralose are shown in Table 4.

[0073] Table 4 Purity and yield of crude sucralose

[0074]

[0075]

[0076] Note: Yield = mass of sucralose / mass of sucralose-6-acetate completely converted to sucralose × 100%.

[0077] Example 3

[0078] The difference between this embodiment and embodiment 1 is that the composition of the mixed solution of ethyl acetate and butyl acetate and the first aqueous solution in step (1) is different, and the remaining steps are the same.

[0079] (1) Extraction step: 1000 mL of the first aqueous solution was placed in a 2 L eggplant-shaped bottle, 300 mL of a mixture of ethyl acetate and butyl acetate (v / v=1:2) was added, and the mixture was stirred and extracted at 60° C. for 15 min. The phases were separated to obtain an organic phase and an aqueous phase. The aqueous phase was subjected to the above extraction step for 5 times. After the extraction was completed, the ester phases were combined as the first ester phase. The aqueous phase obtained from the last extraction was the first aqueous phase (the content of sucralose-6-acetate was 0.07 g / L).

[0080] The volume ratio of ethyl acetate to butyl acetate in the mixed solution of ethyl acetate and butyl acetate is 1:2;

[0081] The composition of the first aqueous solution is shown in Table 5:

[0082] Table 5 Composition of the first aqueous solution

[0083] Components content Sucralose-6-acetate 52.1g / L Sucralose diester 3.4g / L Sucralose-6-acetate 5.8g / L NH4Cl 86.2g / L Other organic impurities 33.7g / L water 89.3wt%

[0084] (2) Concentration and drying step: The first ester phase was concentrated and dried at 80° C. and −0.08 MPa, water was added to the obtained first ester phase concentrate to make 1000 mL, and the mixture was concentrated to 600 mL at 80° C. and −0.08 MPa to obtain a sucralose-6-acetate aqueous solution (ethyl acetate content: 0.35 g / L), which was then transferred to a 1000 mL three-necked flask.

[0085] (3) Alkaline hydrolysis step: The obtained sucralose-6-acetate aqueous solution was cooled to 0°C, and then a 35 wt% potassium hydroxide aqueous solution was added dropwise to mix evenly, and alkaline hydrolysis was performed at 0°C for 5 h. During the alkaline hydrolysis, the pH value of the system was maintained at 12.0. After the alkaline hydrolysis was completed, 30 wt% dilute sulfuric acid was added dropwise to neutralize to pH = 7, and the solution was heated to 60°C for hot filtration to obtain a second aqueous phase (670 mL, sucralose-6-acetate content of 0.05 g / L).

[0086] (4) Separation step: add 1.3L of a mixture of ethyl acetate and butyl acetate (v / v=1:2) to the second aqueous phase, stir and extract at 60°C for 15min, repeat the above extraction operation for the obtained aqueous phase, extract 5 times in total, combine the ester phases obtained from the 1st and 2nd extractions as the second ester phase (2.8L), and the ester phases obtained from the 3rd to 5th extractions with a mixture of ethyl acetate and butyl acetate are successively used as the 1st to 3rd extractions with a mixture of ethyl acetate and butyl acetate of the second aqueous phase in the preparation process of the next batch of crude sucralose. Add 550mL of water to the second ester phase for water washing, wash 5 times, the aqueous phase obtained from the first water washing is the fourth aqueous phase, the fourth aqueous phase is used in step (2) to replace water and mix with the first ester phase concentrate; the aqueous phases obtained from the 2nd to 5th water washings are successively used as the 1st to 4th water washings of the second ester phase in the preparation process of the next batch of crude sucralose, and the ester phase obtained after the washing is the third ester phase. The third ester phase was concentrated and dried at 70° C. and −0.1 MPa (gauge pressure). During the concentration and drying process, a mixed solution of ethyl acetate and butyl acetate was added (the number of additions was 3 times, 300 mL was added each time) for dehydration to ensure that the water was completely removed. A mixed solution of ethyl acetate and butyl acetate was added to the obtained third ester phase concentrate to adjust the sugar content Bx to 45%, thereby obtaining a fourth ester phase.

[0087] (5) Crystallization step: crystallize the fourth ester phase at 45° C. for 24 h, filter and obtain 420 mL of crude sucralose and the fifth ester phase (after equilibration four times); wash the fifth ester phase with water five times (each time with 210 mL of water), the ester phase after washing with water is the sixth ester phase (sucralose content 0.02 g / L), concentrate and dry the sixth ester phase to obtain a mixed solution of recovered ethyl acetate and butyl acetate and a sugar residue; combine the aqueous phases as the fifth aqueous phase, and use the fifth aqueous phase in step (2) to replace water and mix with the first ester phase concentrate.

[0088] (6) According to the operation of steps (1) to (5) (recorded as recycling 0 times), the fourth aqueous phase and the fifth aqueous phase were recycled 15 times, wherein "adding water to 1000 mL of the obtained first ester phase concentrate" in step (1) was modified to "mixing the obtained first ester phase, the fourth aqueous phase and the fifth aqueous phase"; in step (4), the 1st to 3rd extractions of the second aqueous phase with a mixed solution of ethyl acetate and butyl acetate were carried out using the ester phase obtained by the 3rd to 5th extractions of the second aqueous phase with a mixed solution of ethyl acetate and butyl acetate in the preparation process of the previous batch of crude sucralose, and the 4th to 5th extractions of the second aqueous phase with a mixed solution of ethyl acetate and butyl acetate were carried out using a mixed solution of pure ethyl acetate and butyl acetate; the 1st to 4th water washings of the second ester phase were carried out using the aqueous phase obtained by the 2nd to 5th water washings of the second ester phase in the preparation process of the previous batch of crude sucralose, and the 5th water washing of the second ester phase was carried out using pure water; the purity and yield data of the obtained crude sucralose are shown in Table 6.

[0089] Table 6 Purity and yield of crude sucralose

[0090]

[0091] Note: Yield = mass of sucralose / mass of sucralose-6-acetate completely converted to sucralose × 100%.

[0092] Comparative Example 1

[0093] The difference between this comparative example and Example 1 is that the composition of the mixed solution of ethyl acetate and butyl acetate is different. The other steps are the same.

[0094] (1) Extraction step: 1000 mL of the first aqueous solution was placed in a 2 L eggplant-shaped bottle, 300 mL of a mixture of ethyl acetate and butyl acetate (v / v=1:10) was added, and the mixture was stirred and extracted at 60° C. for 15 min. The phases were separated to obtain an organic phase and an aqueous phase. The aqueous phase was subjected to the above extraction step for 5 times. After the extraction was completed, the ester phases were combined as the first ester phase. The aqueous phase obtained from the last extraction was the first aqueous phase (the content of sucralose-6-acetate was 0.05 g / L).

[0095] The volume ratio of ethyl acetate to butyl acetate in the mixed solution of ethyl acetate and butyl acetate is 1:10.

[0096] (2) Concentration and drying step: The first ester phase was concentrated and dried at 80° C. and −0.08 MPa, water was added to the obtained first ester phase concentrate to make 1000 mL, and the concentrate was concentrated to 600 mL at 80° C. and −0.08 MPa to obtain a sucralose-6-acetate aqueous solution (ethyl acetate content: 0.40 g / L), which was then transferred to a 1000 mL three-necked flask.

[0097] (3) Alkaline hydrolysis step: The obtained sucralose-6-acetate aqueous solution was cooled to 0°C, and then a 35 wt% potassium hydroxide aqueous solution was added dropwise to mix evenly, and alkaline hydrolysis was performed at 0°C for 5 h. During the alkaline hydrolysis, the pH value of the system was maintained at 12.0. After the alkaline hydrolysis was completed, 30 wt% dilute sulfuric acid was added dropwise to neutralize to pH = 7, and the solution was heated to 60°C for hot filtration to obtain a second aqueous phase (660 mL, sucralose-6-acetate content of 0.02 g / L).

[0098] (4) Separation step: add 1.3L of a mixture of ethyl acetate and butyl acetate (v / v=1:10) to the second aqueous phase, stir and extract at 60°C for 15min, repeat the above extraction operation for the obtained aqueous phase, extract 5 times in total, combine the ester phases obtained from the 1st and 2nd extractions as the second ester phase (2.7L), and the ester phases obtained from the 3rd to 5th extractions with a mixture of ethyl acetate and butyl acetate are successively used as the 1st to 3rd extractions with a mixture of ethyl acetate and butyl acetate of the second aqueous phase in the preparation process of the next batch of crude sucralose. Add 550mL of water to the second ester phase for water washing, wash 5 times, the aqueous phase obtained from the first water washing is the fourth aqueous phase, the fourth aqueous phase is used in step (2) to replace water and mix with the first ester phase concentrate; the aqueous phases obtained from the 2nd to 5th water washings are successively used as the 1st to 4th water washings of the second ester phase in the preparation process of the next batch of crude sucralose, and the ester phase obtained after the washing is the third ester phase. The third ester phase was concentrated and dried at 70° C. and −0.1 MPa (gauge pressure). During the concentration and drying process, a mixed solution of ethyl acetate and butyl acetate was added (the number of additions was 3 times, 300 mL was added each time) for dehydration to ensure that the water was completely removed. A mixed solution of ethyl acetate and butyl acetate was added to the obtained third ester phase concentrate to adjust the sugar content Bx to 45%, thereby obtaining a fourth ester phase.

[0099] (5) Crystallization step: crystallize the fourth ester phase at 45° C. for 24 h, filter and obtain 430 mL of crude sucralose and the fifth ester phase (after equilibration four times); wash the fifth ester phase with water five times (each time with 210 mL of water), the ester phase after washing with water is the sixth ester phase (sucralose content 0.03 g / L), concentrate and dry the sixth ester phase to obtain a mixed solution of recovered ethyl acetate and butyl acetate and a sugar residue; combine the aqueous phases as the fifth aqueous phase, and use the fifth aqueous phase in step (2) to replace water and mix with the first ester phase concentrate.

[0100] (6) According to the operation of steps (1) to (5) (recorded as recycling 0 times), the fourth aqueous phase and the fifth aqueous phase were recycled 15 times, wherein "adding water to the obtained first ester phase concentrate to 1000 mL" in step (1) was modified to "mixing the obtained first ester phase, the fourth aqueous phase and the fifth aqueous phase"; in step (4), the 1st to 3rd extractions of the second aqueous phase with a mixed solution of ethyl acetate and butyl acetate were carried out using the ester phase obtained by the 3rd to 5th extractions of the second aqueous phase with a mixed solution of ethyl acetate and butyl acetate in the preparation process of the previous batch of crude sucralose, and the 4th to 5th extractions of the second aqueous phase with a mixed solution of ethyl acetate and butyl acetate were carried out using a mixed solution of pure ethyl acetate and butyl acetate; the 1st to 4th water washings of the second ester phase were carried out using the aqueous phase obtained by the 2nd to 5th water washings of the second ester phase in the preparation process of the previous batch of crude sucralose, and the 5th water washing of the second ester phase was carried out using pure water; the purity and yield data of the obtained crude sucralose are shown in Table 7.

[0101] Table 7 Purity and yield of crude sucralose

[0102]

[0103]

[0104] Note: Yield = mass of sucralose / mass of sucralose-6-acetate completely converted to sucralose × 100%.

[0105] Finally, it should be noted that the above content is only used to illustrate the technical solution of the present invention, rather than to limit the scope of protection of the present invention. Simple modifications or equivalent substitutions of the technical solution of the present invention by ordinary technicians in this field do not deviate from the essence and scope of the technical solution of the present invention.

Claims

1. A method for preparing crude sucralose, characterized in that: The steps include: (1) extracting the raw material liquid with a mixed solution of ethyl acetate and butyl acetate to obtain a first ester phase and a first aqueous phase; the raw material liquid is an aqueous solution including sucralose-6-acetate, sucralose diester and tetrachlorosucrose-6-acetate; (2) concentrating the first ester phase in step (1) to dryness, adding water to dissolve, and concentrating to obtain a sucralose-6-acetate aqueous solution; (3) subjecting the aqueous solution of sucralose-6-acetate described in step (2) to alkaline hydrolysis, neutralization, and filtering to obtain a second aqueous phase; (4) extracting the second aqueous phase in step (3) with a mixture of ethyl acetate and butyl acetate to obtain a second ester phase and a third aqueous phase; (5) washing the second ester phase in step (4) with water to obtain a third ester phase and a fourth aqueous phase; (6) After the third ester phase in step (5) is concentrated and dried, a mixture of ethyl acetate and butyl acetate is added and mixed to obtain a concentrate, and then a mixture of ethyl acetate and butyl acetate is added to obtain a fourth ester phase; (7) crystallizing the fourth ester phase in step (6) to obtain crude sucralose and a fifth ester phase; (8) washing the fifth ester phase in step (7) with water to obtain a sixth ester phase and a fifth aqueous phase; (9) repeating steps (1) to (8) at least twice, concentrating and drying the sixth ester phase in step (8) to obtain crude sucralose; The volume ratio of ethyl acetate to butyl acetate in the mixed solution in each step is 1:0.5-3.

2. The method according to claim 1, characterized in that The volume ratio of the raw material liquid to the mixed liquid in step (1) is 10:1-5; The raw material liquid in step (1) comprises sucralose-6-acetate, sucralose diester, tetrachlorosucrose-6-acetate, NH4Cl, other organic impurities and water.

3. The method according to claim 2, characterized in that The content of sucralose-6-acetate is 40-70 g / L, the content of sucralose diester is 2-10 g / L, the content of sucralose-6-acetate is 2-10 g / L, the content of NH4Cl is 70-90 g / L, the content of other organic impurities is 20-50 g / L and the content of water is 70-90 wt%.

4. The method according to claim 1, characterized in that The extraction conditions in steps (1) and (4) are 55-65° C. for 10-20 min; The extractions in steps (1) and (4) are performed at least twice.

5. The method according to claim 1, characterized in that The concentration in step (2) is concentrated to 50-70% of the volume of the original solvent; The alkaline hydrolysis reaction in step (3) is as follows: adding alkaline solution at -4 to 4°C and reacting for 4-6 hours, wherein the concentration of the alkaline solution is 25-45wt%; the pH of the reaction system of the alkaline hydrolysis reaction is 11-13; and the alkali in the alkaline solution is potassium hydroxide and / or sodium hydroxide.

6. The method according to claim 1, characterized in that The number of water washings in steps (5) and (8) is at least 2 times.

7. The method according to any one of claims 1 to 6, characterized in that: The extraction in step (4) is divided into 5 times, wherein the ester phases obtained from the 1st to 2nd extractions are combined as the second ester phase; the ester phases obtained from the 3rd to 5th extractions successively replace the mixed solution of ethyl acetate and butyl acetate used in the 1st to 3rd extractions of the second aqueous phase in step (3).

8. The method according to any one of claims 1 to 6, characterized in that: The number of water washings in step (5) is 5 times, and the aqueous phase obtained from the first water washing is used as the fourth aqueous phase; the fourth aqueous phase replaces the water in step (2); the aqueous phases obtained from the second to fifth water washings are used in sequence for the first to fourth water washings of the second ester phase in step (5), and the ester phases obtained from the five water washings are combined as the third ester phase.

9. The method according to any one of claims 1 to 6, characterized in that: The fifth aqueous phase in step (8) replaces the water in step (2).

10. Use of a mixed solution of ethyl acetate and butyl acetate in the preparation of crude sucralose, wherein the volume ratio of ethyl acetate to butyl acetate in the mixed solution is 1:0.5-3.

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