A kind of preparation method of sucralose

Abstract

The present invention provides a method for preparing sucralose, and belongs to the technical field of fine chemicals. The method for preparing sucralose provided by the present invention comprises the following steps: mixing sucrose, N, N-dimethylformamide, trichloroethane and thionyl chloride, performing a chlorination reaction, and obtaining a chlorinated product liquid; adjusting the pH value of the chlorinated product liquid to alkaline, performing a decomposition reaction, and obtaining tetrachlorosucrose; mixing the tetrachlorosucrose, water and an alkaline hydrolysis agent, performing an alkaline hydrolysis reaction, and obtaining sucralose. The present invention abandons the traditional method of protecting the hydroxyl group at position 6 of sucrose, and directly uses sucrose as a raw material for chlorination to prepare tetrachlorosucrose. The chlorine atom group at position 6 of tetrachlorosucrose has higher activity than other groups, and can be dechlorinated at position 6 under the action of an alkaline hydrolysis agent, and finally obtains sucralose. The method provided by the present invention has a short process and a high yield of sucralose.

Description

Technical Field

[0001] The invention relates to the technical field of fine chemicals, and in particular to a method for preparing sucralose. Background Art

[0002] Sucralose (TGS), commonly known as sucralose, is a sweetener developed by Tate & Lyle and the University of London in the United Kingdom and patented in 1976. It is currently the only functional sweetener using sucrose as raw material, and its sweetness can reach 600 times that of sucrose. Due to its pure taste, non-metabolism, high sweetness, no calories, good stability, and high safety, it has been widely used in beverages, food, daily chemicals, medicine and other fields, and is currently one of the best functional sweeteners.

[0003] At present, the production process of sucralose mainly includes esterification, chlorination, alcoholysis, separation and purification, etc. Its reaction mechanism is to use sucrose as raw material, N,N-dimethylformamide (DMF) as solvent and dehydrating agent, and organic tin ester as catalyst to protect the hydroxyl group at position 6 of sucrose to generate sucrose-6-butyl ester; then chlorinate in the presence of chlorination reagents such as thionyl chloride or phosgene to generate sucralose-6-acetate; finally, react in a methanol / sodium methoxide alcoholysis system or other alkaline hydrolysis system to generate sucralose. This process is long, the amount of solvent used is large, there are many side reactions, and the yield of sucralose is not high, about 40%.

[0004] In order to improve the yield of sucralose and reduce costs, many research institutes and peers have developed a number of processes with application value in various stages, such as the use of alkaline ion exchange resin method (CN112409419A, CN102336787A), alkali metal oxide method (CN113004345A, CN104004032A, CN112805291A) or alkali metal hydroxide method (CN181 4609A, CN101012250A, CN102321122A), to increase the yield of sucralose from sucralose-6-acetate, reduce the content of acetic acid in the system, and thus improve the product quality; another example is to recover sucralose-6-acetate from the sucralose-6-acetate purification mother liquor by oxidation or alkaline hydrolysis, thereby increasing the yield of sucralose (CN113677689A, CN113939524A).

[0005] However, even with the above-mentioned technological improvements, the main process of sucralose has not changed, and there is still a problem of long process flow, and the yield of sucralose is about 45%, which is still relatively low. Summary of the invention

[0006] The object of the present invention is to provide a method for preparing sucralose. The method provided by the present invention has a short process and a high yield of sucralose.

[0007] In order to solve the above technical problems, the technical solution adopted by the present invention is:

[0008] The present invention provides a method for preparing sucralose, comprising the following steps:

[0009] Mixing sucrose, N,N-dimethylformamide, trichloroethane and thionyl chloride to perform a chlorination reaction to obtain a chlorinated product solution; adjusting the pH value of the chlorinated product solution to alkaline, performing a decomposition reaction to obtain tetrachlorosucrose;

[0010] The sucralose, water and an alkaline hydrolysis agent are mixed to perform an alkaline hydrolysis reaction to obtain sucralose.

[0011] Preferably, the mixing of sucrose, N,N-dimethylformamide, trichloroethane and thionyl chloride comprises: mixing sucrose with N,N-dimethylformamide to obtain a sucrose constant volume solution; sequentially adding the thionyl chloride and the sucrose constant volume solution dropwise to the trichloroethane;

[0012] The sucrose constant volume solution also includes a vacuum dehydration treatment before use, the vacuum dehydration treatment temperature is 50-70° C., and the vacuum degree is -0.1 MPa; the vacuum dehydration treatment ends when the water content in the condensed and collected N,N-dimethylformamide is less than 0.3wt%;

[0013] The thionyl chloride and the sucrose constant volume solution are added dropwise at -5 to 5°C.

[0014] Preferably, the dosage ratio of the sucrose to N,N-dimethylformamide is 1 g: (3-5) mL; the molar ratio of the sucrose to thionyl chloride is 1: (5-10); the volume ratio of the thionyl chloride to trichloroethane is 1: (4-5);

[0015] The chlorination reaction comprises a first stage insulation reaction, a first heating, a second stage insulation reaction, a second heating, a third stage insulation reaction, a third heating and a fourth stage insulation reaction in sequence; the temperature of the first stage insulation reaction is 10-20°C, and the insulation time is 0.5-1h; the temperature of the second stage insulation reaction is 35-45°C, and the insulation time is 0.5-1h; the temperature of the third stage insulation reaction is 75-85°C, and the insulation time is 1-1.5h; the temperature of the fourth stage insulation reaction is 100-110°C, and the insulation time is 1.5-2h.

[0016] Preferably, the pH value of the chlorinated product solution is adjusted to alkalinity at 0-10°C; the alkalinity is pH=9-11;

[0017] The reagent used to adjust the pH value of the chlorinated product solution is an inorganic alkali solution.

[0018] Preferably, the temperature of the decomposition reaction is 0-10° C., and the insulation time is 0.5-1 h.

[0019] Preferably, the decomposition reaction further comprises:

[0020] The pH value of the decomposition product liquid obtained by the decomposition reaction is adjusted to 6 to 8 by using an inorganic acid to obtain a chlorinated neutralization liquid;

[0021] The chlorinated neutralized liquid is separated and purified to obtain tetrachlorosucrose.

[0022] Preferably, the separation and purification comprises:

[0023] The chlorinated neutralized liquid is concentrated to dryness, and the residue is mixed with water to obtain a first aqueous phase; the content of N,N-dimethylformamide in the first aqueous phase is less than 5 g / L, and the content of trichloroethane is less than 1 g / L;

[0024] The first aqueous phase is extracted with butyl acetate to obtain a first ester phase and a second aqueous phase; the number of extractions is 4 to 6 times, and the volume ratio of butyl acetate to the first aqueous phase used in each extraction is (0.5 to 2): 1; the extraction is based on the content of sucralose in the second aqueous phase being less than 0.5 g / L;

[0025] The first ester phase is decolorized and washed with water in sequence to obtain a second ester phase and a third aqueous phase; the decolorization material is activated carbon, and the mass ratio of the activated carbon to the volume ratio of the first ester phase is (0.1-0.3) g:100 mL; the washing is performed 4-6 times, and the volume ratio of water used in each washing to the first ester phase is (0.1-0.2):1; the third aqueous phase is extracted with butyl acetate to obtain a butyl acetate phase and a fourth aqueous phase, and the butyl acetate phase is used to extract the next batch of the first aqueous phase; the third aqueous phase is extracted with butyl acetate 1-2 times, and the volume ratio of butyl acetate used in each extraction to the third aqueous phase is (0.5-2):1; the third aqueous phase is extracted with butyl acetate to make the content of sucralose in the fourth aqueous phase less than 0.5 g / L as a benchmark;

[0026] The second ester phase is concentrated to dryness to obtain sucralose.

[0027] Preferably, the alkaline hydrolysis agent comprises tetramethylammonium hydroxide aqueous solution, tetraethylammonium hydroxide aqueous solution or tetrabutylammonium hydroxide aqueous solution; the concentration of the alkaline hydrolysis agent is 10 or 25 wt%.

[0028] Preferably, the conditions of the alkaline hydrolysis reaction include: pH value of 10.5-12.5, temperature of 0-10° C., and insulation time of 1-4 h.

[0029] Preferably, the alkaline hydrolysis reaction further comprises:

[0030] The pH value of the alkaline hydrolysis product solution obtained by the alkaline hydrolysis reaction is adjusted to 6-8 by using hydrochloric acid to obtain a crude sucralose product aqueous solution;

[0031] The crude sucralose aqueous solution is concentrated to dryness, the residue is dissolved in methanol, the chloride salt is precipitated, and then the solid-liquid separation is performed, the obtained filtrate is concentrated to dryness, and the residue is dissolved in water to obtain an aqueous solution containing sucralose; the volume of the methanol is 4 to 6 times the volume of the crude sucralose aqueous solution; the content of methanol in the aqueous solution containing sucralose is less than 0.3 g / L.

[0032] The present invention provides a method for preparing sucralose, comprising the following steps: mixing sucrose, N,N-dimethylformamide, trichloroethane and thionyl chloride, performing a chlorination reaction, and obtaining a chlorinated product liquid; adjusting the pH value of the chlorinated product liquid to alkaline, performing a decomposition reaction, and obtaining tetrachlorosucrose; mixing the tetrachlorosucrose, water and an alkaline hydrolysis agent, performing an alkaline hydrolysis reaction, and obtaining sucralose. The present invention abandons the traditional method of protecting the hydroxyl group at position 6 of sucrose, and directly uses sucrose as a raw material for chlorination to prepare tetrachlorosucrose. The chlorine atom group at position 6 of tetrachlorosucrose has higher activity than other groups, and can be dechlorinated at position 6 under the action of an alkaline hydrolysis agent to finally obtain sucralose. The method provided by the present invention has a short process and a high yield of sucralose.

[0033] Furthermore, the method provided by the present invention has at least the following beneficial effects:

[0034] 1. Butyl acetate is used as the extractant. Sucralose has a high solubility in butyl acetate, which can realize the effective separation of sucralose from the system after the chlorination reaction, which is beneficial to reducing the difficulty of subsequent reactions and product purification; 2. The amount of N,N-dimethylformamide solvent used is greatly reduced, which is beneficial to reducing the cost and difficulty of solvent recovery, avoiding the problem of using a large amount of N,N-dimethylformamide solvent in the traditional process, resulting in the easy generation of N,N-dimethylacetamide (DMAC) and tetramethylurea by-products during the solvent recovery process, and relieving the pressure of subsequent environmental protection treatment; 3. No acetic acid by-product is generated, which solves the problem of acetic acid corrosion to equipment and adverse effects on product quality in the traditional process; 4. The use of organic tin catalyst is abandoned, thereby eliminating the threat of metal tin to products and the environment; 5. Shortening the reaction process is beneficial to reducing the occurrence of side reactions, with low cost, less equipment investment, high stability, and good industrial application value. BRIEF DESCRIPTION OF THE DRAWINGS

[0035] Figure 1 The present invention is a process flow chart for preparing sucralose. DETAILED DESCRIPTION

[0036] The present invention is further described below in conjunction with embodiments and drawings.

[0037] The present invention provides a method for preparing sucralose, comprising the following steps:

[0038] Mixing sucrose, N,N-dimethylformamide, trichloroethane and thionyl chloride to perform a chlorination reaction to obtain a chlorinated product solution; adjusting the pH value of the chlorinated product solution to alkaline, performing a decomposition reaction to obtain tetrachlorosucrose;

[0039] The sucralose, water and an alkaline hydrolysis agent are mixed to perform an alkaline hydrolysis reaction to obtain sucralose.

[0040] In the present invention, unless otherwise specified, the raw materials used are commercially available products well known to those skilled in the art; unless otherwise specified, the water used in the present invention is pure water.

[0041] The present invention mixes sucrose, N,N-dimethylformamide, trichloroethane and thionyl chloride, performs chlorination reaction, and obtains chlorinated product liquid. In the present invention, the dosage ratio of sucrose to N,N-dimethylformamide is preferably 1g:(3-5)mL, more preferably 1g:4mL; the molar ratio of sucrose to thionyl chloride is preferably 1:(5-10), more preferably 1:(7-8); the volume ratio of thionyl chloride to trichloroethane is preferably 1:(4-5), more preferably 1:4.5.

[0042] In the present invention, the mixing of sucrose, N,N-dimethylformamide, trichloroethane and thionyl chloride preferably includes: mixing sucrose with N,N-dimethylformamide to obtain a sucrose constant volume solution; sequentially adding the thionyl chloride and the sucrose constant volume solution to the trichloroethane. In the present invention, the sucrose constant volume solution preferably also includes a vacuum dehydration treatment before use, and the temperature of the vacuum dehydration treatment is preferably 50-70°C, specifically 50°C, 60°C or 70°C, and a higher temperature is prone to cause sucrose caramelization; the vacuum degree is preferably -0.1MPa, and the vacuum degree of the present invention is specifically the instrument pressure. The present invention preferably mixes sucrose with N,N-dimethylformamide, heats to completely dissolve the sucrose, and then performs a vacuum dehydration treatment; the heating temperature is preferably 70-80°C, specifically 70°C, 75°C or 80°C. In the present invention, the vacuum dehydration treatment is preferably terminated when the water content in the condensed and collected N,N-dimethylformamide is less than 0.3wt%. The present invention preferably removes water from sucrose by vacuum dehydration. In the present invention, the sugar content in the sucrose constant volume solution after vacuum dehydration is preferably 250-350 g / L. In the present invention, the dripping of the thionyl chloride and the sucrose constant volume solution is preferably carried out at -5 to 5°C, more preferably -2 to 2°C. The present invention has no special limitation on the dripping rate of the thionyl chloride and the sucrose constant volume solution, as long as the system temperature is controlled within the above range.

[0043] In the present invention, the chlorination reaction preferably includes a first stage insulation reaction, a first heating, a second stage insulation reaction, a second heating, a third stage insulation reaction, a third heating and a fourth stage insulation reaction in sequence; the temperature of the first stage insulation reaction is preferably 10-20°C, more preferably 15°C, and the insulation time is preferably 0.5-1h; after the first stage insulation reaction, the system temperature is raised to the temperature of the second stage insulation reaction by the first heating; the temperature of the second stage insulation reaction is preferably 35-45°C, more preferably 40°C, and the insulation time is preferably 0.5-1h; after the second stage insulation reaction, the system temperature is raised to the temperature of the third stage insulation reaction by the second heating; the temperature of the third stage insulation reaction is preferably 75-85°C, more preferably 80°C, and the insulation time is preferably 1-1.5h; after the third stage insulation reaction, the system temperature is raised to the temperature of the fourth stage insulation reaction by the third heating; the temperature of the fourth stage insulation reaction is preferably 100-110°C, more preferably 105°C, and the insulation time is preferably 1.5-2h. The present invention divides the chlorination reaction into the above-mentioned stages, which can effectively react and convert sucrose into tetrachlorosucrose, which is beneficial to the subsequent preparation and separation of sucralose.

[0044] After obtaining the chlorinated product liquid, the present invention adjusts the pH value of the chlorinated product liquid to alkaline, performs a decomposition reaction, and obtains tetrachlorosucrose. In the present invention, adjusting the pH value of the chlorinated product liquid to alkaline is preferably carried out under the conditions of 0 to 10°C, more preferably 5°C; the alkalinity is preferably pH=9 to 11, more preferably 10. In the present invention, the reagent used to adjust the pH value of the chlorinated product liquid is preferably an inorganic alkali solution, and the inorganic alkali solution preferably includes ammonia water, NaOH solution or KOH solution, and the concentration of the inorganic alkali solution is preferably 15 to 30wt%. In the present invention, the temperature of the decomposition reaction is preferably 0 to 10°C, more preferably 5°C; the insulation time is preferably 0.5 to 1h.

[0045] In the present invention, the decomposition reaction preferably further comprises:

[0046] The pH value of the decomposition product liquid obtained by the decomposition reaction is adjusted to 6 to 8 to obtain a chlorinated neutralization liquid;

[0047] The chlorinated neutralized liquid is separated and purified to obtain tetrachlorosucrose.

[0048] The present invention adjusts the pH value of the decomposition product liquid obtained by the decomposition reaction to 6-8 to obtain a chlorinated neutralized liquid. In the present invention, the reagent used to adjust the pH value of the decomposition product liquid is preferably an inorganic acid, and the inorganic acid is preferably hydrochloric acid; the concentration of the inorganic acid is preferably 35wt%.

[0049] After obtaining the chlorinated neutralized solution, the present invention separates and purifies the chlorinated neutralized solution to obtain tetrachlorosucrose. In the present invention, the separation and purification preferably includes:

[0050] Concentrating the chlorinated neutralized liquid to dryness, and mixing the residue with water to obtain a first aqueous phase;

[0051] extracting the first aqueous phase with butyl acetate to obtain a first ester phase;

[0052] Decolorizing and washing the first ester phase in sequence to obtain a second ester phase;

[0053] The second ester phase is concentrated to dryness to obtain sucralose.

[0054] The present invention concentrates the chlorinated neutralized liquid to dryness, mixes the residue with water, and obtains a first aqueous phase. The present invention preferably removes N,N-dimethylformamide and trichloroethane in the chlorinated neutralized liquid by concentrating the chlorinated neutralized liquid to dryness, and the N,N-dimethylformamide and trichloroethane can be recycled and reused. In the present invention, in order to facilitate the sufficient removal of N,N-dimethylformamide and trichloroethane, it is preferred to add water to assist desolventization during the concentration process. In the present invention, the content of N,N-dimethylformamide in the first aqueous phase is preferably less than 5g / L, and the content of trichloroethane is preferably less than 1g / L.

[0055] After obtaining the first aqueous phase, the present invention uses butyl acetate to extract the first aqueous phase to obtain a first ester phase. In the present invention, the extraction is preferably carried out at room temperature. In the present invention, the number of extractions with butyl acetate is preferably 4 to 6 times; the volume ratio of butyl acetate used in each extraction to the first aqueous phase is preferably (0.5 to 2): 1, more preferably 1: 1; the present invention preferably combines the ester phases obtained from the first two butyl acetate extractions as the first ester phase; the ester phases obtained from the remaining batches of butyl acetate extractions are used for the butyl acetate extraction of the first aqueous phase in the next batch of sucralose preparation process. Specifically, taking 6 extractions as an example, the ester phase obtained from the third butyl acetate extraction is preferably used for the first butyl acetate extraction of the first aqueous phase in the next batch of sucralose preparation process, and the ester phase obtained from the fourth butyl acetate extraction is preferably used for the next The ester phase obtained by the second butyl acetate extraction and the fifth butyl acetate extraction of the first aqueous phase in the preparation process of a batch of sucralose is preferably used for the third butyl acetate extraction of the first aqueous phase in the preparation process of the next batch of sucralose, and the ester phase obtained by the sixth butyl acetate extraction is preferably used for the fourth butyl acetate extraction of the first aqueous phase in the preparation process of the next batch of sucralose (that is, the ester phases obtained by the third to sixth butyl acetate extractions are sequentially used for the first to fourth butyl acetate extractions of the first aqueous phase in the preparation process of the next batch of sucralose; preferably, the fifth to sixth butyl acetate extractions of the first aqueous phase in the preparation process of the next batch of sucralose are preferably carried out using pure butyl acetate). In the present invention, the first aqueous phase is preferably extracted with butyl acetate to obtain a second aqueous phase, and the extraction is preferably based on the content of sucralose in the second aqueous phase being less than 0.5 g / L; the second aqueous phase is high-salt wastewater, which can be treated according to conventional methods in the art.

[0056] After obtaining the first ester phase, the present invention decolorizes and washes the first ester phase in sequence to obtain the second ester phase. In the present invention, the material used for decolorization is preferably activated carbon, and the volume ratio of the mass of the activated carbon to the first ester phase is preferably (0.1-0.3) g:100 mL, more preferably 0.2 g:100 mL. After the decolorization, the present invention preferably filters the obtained decolorized liquid and washes the obtained filtrate with water. In the present invention, the number of water washings is preferably 4-6 times; the volume ratio of the water used for each water washing to the first ester phase is preferably (0.1-0.2):1, more preferably 0.15:1; the present invention preferably combines the aqueous phases obtained from the first two water washings as the third aqueous phase; the aqueous phases obtained from the remaining batches of water washings are preferably used for the washing of the first ester phase in the preparation process of the next batch of sucralose. Specifically, taking 6 water washings as an example, the aqueous phase obtained from the third water washing is used for the first water washing of the first ester phase in the preparation process of the next batch of sucralose, and the aqueous phase obtained from the fourth water washing is used for the first water washing of the first ester phase in the preparation process of the next batch of sucralose. The aqueous phase obtained from the 5th water washing is used for the 2nd water washing of the first ester phase in the next batch of sucralose preparation process, the aqueous phase obtained from the 5th water washing is used for the 3rd water washing of the first ester phase in the next batch of sucrose preparation process, and the aqueous phase obtained from the 6th water washing is used for the 4th water washing of the first ester phase in the next batch of sucrose preparation process (i.e., the aqueous phases obtained from the 3rd to 6th water washings are used in sequence for the 1st to 4th water washings of the first ester phase in the next batch of sucralose preparation process; preferably, the 5th to 6th water washings of the second ethyl ester phase in the next batch of sucralose crude preparation process are preferably carried out with pure water). In the present invention, the water washing preferably also obtains a third aqueous phase; after obtaining the third aqueous phase, it is preferably further included: extracting the third aqueous phase with butyl acetate to obtain a butyl acetate phase, and the butyl acetate phase is used to extract the next batch of the first aqueous phase. In the present invention, the number of times the third aqueous phase is extracted with butyl acetate is preferably 1 to 2 times, and the volume ratio of butyl acetate used in each extraction to the third aqueous phase is preferably (0.5 to 2):1. In the present invention, the third aqueous phase is extracted with butyl acetate to obtain a fourth aqueous phase, and the extraction is based on the content of sucralose in the fourth aqueous phase being less than 0.5 g / L; the fourth aqueous phase is wastewater and can be treated according to conventional methods in the art.

[0057] After obtaining the second ester phase, the present invention concentrates the second ester phase to dryness to obtain sucralose. In the present invention, the present invention preferably removes butyl acetate by concentrating the second ester phase to dryness, and the butyl acetate can be recycled and reused. In the present invention, in order to facilitate the sufficient removal of butyl acetate, water is preferably added during the concentration process to assist desolventization. In the present invention, the sucralose obtained after the second ester phase is concentrated to dryness is preferably directly subjected to a subsequent alkaline hydrolysis reaction.

[0058] After obtaining sucralose, the present invention mixes the sucralose, water and an alkaline hydrolysis agent to perform an alkaline hydrolysis reaction to obtain sucralose. In the present invention, the alkaline hydrolysis agent preferably includes an aqueous solution of tetramethylammonium hydroxide, an aqueous solution of tetraethylammonium hydroxide or an aqueous solution of tetrabutylammonium hydroxide; the concentration of the alkaline hydrolysis agent is preferably 10wt% or 25wt% (both are commercially available products). In the present invention, the sucralose obtained after the second ester phase is concentrated to dryness is preferably mixed with water to obtain an aqueous solution of sucralose, and then an alkaline hydrolysis agent is added to the aqueous solution of sucralose; in the present invention, the content of butyl acetate in the aqueous solution of sucralose is preferably <0.1g / L. In the present invention, the conditions for the alkaline hydrolysis reaction preferably include: the pH value is preferably 10.5-12.5, more preferably 11.5; the temperature is preferably 0-10°C, more preferably 5°C; the insulation time is preferably 1-4h, more preferably 2.5h. The present invention preferably performs an alkaline hydrolysis reaction under the above conditions, which can ensure the stability and high selectivity of the reaction and is conducive to the generation of sucralose.

[0059] In the present invention, the alkaline hydrolysis reaction preferably further comprises:

[0060] The pH value of the alkaline hydrolysis product solution obtained by the alkaline hydrolysis reaction is adjusted to 6-8 by using hydrochloric acid to obtain a crude sucralose product aqueous solution;

[0061] The crude sucralose aqueous solution is concentrated to dryness, the residue is dissolved in methanol, the chloride salt is precipitated, and then solid-liquid separation is performed. The obtained filtrate is concentrated to dryness, and the residue is dissolved in water to obtain an aqueous solution containing sucralose.

[0062] In the present invention, the concentration of hydrochloric acid used to adjust the pH value of the alkaline hydrolysis product liquid is preferably 35wt%. In the present invention, the volume of the methanol is preferably 4 to 6 times the volume of the crude sucralose aqueous solution. In the present invention, sucralose is soluble in methanol, and chloride salt is insoluble in methanol, so the residue obtained by concentrating the crude sucralose aqueous solution to dryness can be dissolved in methanol to precipitate chloride salt, and then removed by solid-liquid separation. In the present invention, the content of methanol in the aqueous solution containing sucralose is preferably <0.3g / L.

[0063] After obtaining the aqueous solution containing sucralose, the present invention preferably uses a method well known to those skilled in the art to separate sucralose, which will not be described in detail here.

[0064] The preparation method of sucralose provided by the present invention is described in detail below in conjunction with the examples, but they should not be construed as limiting the scope of protection of the present invention.

[0065] The contents of sucrose, sucralose and tetrachlorosucrose in the following examples were measured by high performance liquid chromatography (HPLC) based on the external standard method under the following conditions. The analytical conditions of the high performance liquid chromatography include: Shimadzu high performance liquid chromatograph, equipped with RID-10A differential refractive index detection, LC-10ADVP high pressure pump, CTO-10ASVP constant temperature box; the chromatographic column is Agilent XDBC18 column (250mm×4.6mm, 5μm); the mobile phase is methanol and 0.125wt% dipotassium hydrogen phosphate aqueous solution, and the volume ratio of methanol to dipotassium hydrogen phosphate aqueous solution is 4:6; the column temperature is 40°C; the mobile phase flow rate is 1.0mL / min; wherein methanol is chromatographically pure, dipotassium hydrogen phosphate is analytically pure, and water is ultrapure water.

[0066] Example 1

[0067] according to Figure 1 The process flow chart shown in the figure is used to prepare sucralose, and the specific steps are as follows:

[0068] (1) Dehydration step: 200 g of sucrose and 600 mL of N,N-dimethylformamide (DMF) were added to a three-necked flask in sequence, heated to 80° C. to completely dissolve, then cooled to 50° C., evacuated to a vacuum degree of -0.1 MPa (instrument pressure), and dehydrated. When the water content in the condensed and collected DMF was 0.29 wt %, the dehydration was completed, and 572 mL of sucrose constant volume solution was obtained, and the sucrose content in the sucrose constant volume solution was 349.28 g / L.

[0069] (2) Chlorination reaction step: add 1700 mL of trichloroethane to a three-necked flask, and drop 424 mL of thionyl chloride into the trichloroethane, and control the system temperature to -5°C during the dropwise addition; after the dropwise addition of thionyl chloride is completed, drop 572 mL of the sucrose constant volume solution obtained in step (1); after the dropwise addition of the sucrose constant volume solution is completed, heat the mixture to 10°C and keep the reaction for 1 hour, heat the mixture to 35°C and keep the reaction for 1 hour, heat the mixture to 75°C and keep the reaction for 1.5 hours, and heat the mixture to 100°C and keep the reaction for 2 hours; after the reaction is completed, cool the resulting product system to 0°C, drop 20 wt% ammonia water under stirring, adjust the pH value of the system to 9, and react for 1 hour, then adjust the pH value of the resulting product system to 6 with 35 wt% hydrochloric acid, and obtain 2801 mL of chlorinated neutralization solution.

[0070] (3) Separation step: 2801 mL of the chlorinated neutralized solution obtained in step (2) was concentrated to dryness, DMF and trichloroethane were recovered, pure water was added to assist desolventization during the concentration process, and finally the residue was diluted to 1000 mL with pure water to obtain a first aqueous phase, in which the DMF content was 4.23 g / L and the trichloroethane content was 0.72 g / L. Under room temperature (25° C.), the first aqueous phase was extracted with butyl acetate for 6 times, and the volume of butyl acetate used for each extraction was 500 mL. During the extraction process, the ester phases obtained from the first two extractions were combined and recorded as the first ester phase, totaling 1183 mL. The ester phases obtained from the last four extractions were used in the butyl acetate extraction step of the first aqueous phase in the next batch of sucralose preparation process; the raffinate aqueous phase was recorded as the second aqueous phase, totaling 703 mL, and was treated as wastewater. The sucralose content in the second aqueous phase was 0.3 g / L. 3.54 g of activated carbon was added to the first ester phase for decolorization, and then the activated carbon was removed by filtration. The first ester phase after decolorization was washed with pure water gradient for 6 times, and the volume of pure water used for each washing was 118 mL, to obtain 1070 mL of the second ester phase. During the pure water washing process, the aqueous phases obtained from the first 2 washings were combined and recorded as the third aqueous phase, a total of 281 mL, and the aqueous phases obtained from the last 4 washings were used in the washing step of the first ester phase in the preparation process of the next batch of sucralose. The third aqueous phase was extracted with butyl acetate 2 times, and the volume of butyl acetate used for each extraction was 140 mL, to obtain 300 mL of butyl acetate phase, which was used for the next batch of extraction of the first aqueous phase, and the residual aqueous phase was recorded as the fourth aqueous phase, which was treated as wastewater. The sucralose content in the fourth aqueous phase was 0.3 g / L. The second ester phase is concentrated to dryness to recover butyl acetate. Pure water is added to assist desolventization during the concentration process. Finally, the residue is diluted to 1000 mL with pure water to obtain a tetrachlorosucrose aqueous solution, wherein the tetrachlorosucrose content of the tetrachlorosucrose aqueous solution is 174.55 g / L and the butyl acetate content is 0.07 g / L.

[0071] (4) Alkaline hydrolysis step: 1000 mL of the sucralose aqueous solution obtained in step (3) was cooled to 0° C., and a 10 wt % tetraethylammonium hydroxide aqueous solution was added dropwise. During the addition, the system temperature was controlled to be 0° C. The addition was stopped when the pH value of the system was 11.5, and the reaction was then kept warm for 2.5 h. After the reaction was completed, the sucralose content in the product system was 0.3 g / L. 35 wt % hydrochloric acid was added dropwise to the product system until the pH value of the system was 8, to obtain 1710 mL of a crude sucralose aqueous solution. The crude sucralose aqueous solution is concentrated to dryness, methanol is added for azeotropy during the concentration process, and then the obtained residue is diluted to 6840 mL with methanol. At this time, tetraethylammonium chloride is precipitated from the system and separated by suction filtration; the filtrate is concentrated to dryness, and methanol is recovered. Pure water is added to azeotropy with methanol during the concentration process to ensure low residual methanol. Finally, the obtained residue is diluted to 1710 mL with pure water to obtain a sucralose aqueous solution, wherein the methanol content of the sucralose aqueous solution is 0.1 g / L, the sucralose content is 83.17 g / L, and the sucralose yield is 61.2%.

[0072] Example 2

[0073] (1) Dehydration step: 200 g of sucrose and 800 mL of N,N-dimethylformamide (DMF) were added to a three-necked flask in sequence, heated to 75° C. for complete dissolution, then cooled to 60° C., evacuated to a vacuum degree of -0.1 MPa (instrument pressure), and dehydrated. When the water content in the condensed and collected DMF was 0.25 wt %, the dehydration was completed, and 663 mL of sucrose constant volume solution was obtained, wherein the sucrose content in the sucrose constant volume solution was 301.32 g / L.

[0074] (2) Chlorination reaction step: add 1350 mL of trichloroethane to a three-necked flask, add 300 mL of thionyl chloride dropwise to the trichloroethane, and control the system temperature to be 0° C. during the addition process; after the addition of thionyl chloride is completed, add 663 mL of the sucrose constant volume solution obtained in step (1) dropwise; after the addition of the sucrose constant volume solution is completed, heat the mixture to 15° C. and keep the mixture for 45 min, heat the mixture to 40° C. and keep the mixture for 45 min, heat the mixture to 80° C. and keep the mixture for 1 h 45 min, and heat the mixture to 105° C. and keep the mixture for 1 h 15 min; after the reaction is completed, cool the obtained product system to 5° C., add 20 wt % ammonia water dropwise under stirring, adjust the pH value of the system to 10, and react for 45 min, then adjust the pH value of the obtained product system to 7 with 35 wt % hydrochloric acid, to obtain 2250 mL of chlorinated neutralization solution.

[0075] (3) Separation step: 2250 mL of the chlorinated neutralized solution obtained in step (2) was concentrated to dryness, DMF and trichloroethane were recovered, pure water was added to assist desolventization during the concentration process, and finally the residue was diluted to 1000 mL with pure water to obtain a first aqueous phase, in which the DMF content was 3.77 g / L and the trichloroethane content was 0.67 g / L. Under room temperature (25° C.), the first aqueous phase was extracted 5 times with butyl acetate, and the volume of butyl acetate used for each extraction was 1000 mL. During the extraction process, the ester phases obtained from the first two extractions were combined and recorded as the first ester phase, totaling 2186 mL. The ester phases obtained from the last three extractions were used in the butyl acetate extraction step of the first aqueous phase in the next batch of sucralose preparation process; the raffinate aqueous phase was recorded as the second aqueous phase, totaling 691 mL, and was treated as wastewater. The sucralose content in the second aqueous phase was 0.2 g / L. 4.36g of activated carbon was added to the first ester phase for decolorization, and then the activated carbon was removed by filtration. The first ester phase after decolorization was washed with pure water gradient for 5 times, and the volume of pure water used for each washing was 438mL, to obtain 2065mL of the second ester phase. During the pure water washing process, the aqueous phases obtained from the first two washings were combined and recorded as the third aqueous phase, a total of 908mL, and the aqueous phases obtained from the last three washings were used in the washing step of the first ester phase in the preparation process of the next batch of sucralose. The third aqueous phase was extracted once with 908mL of butyl acetate to obtain 932mL of butyl acetate phase, which was used for the next batch of extraction of the first aqueous phase. The residual aqueous phase was recorded as the fourth aqueous phase and treated as wastewater. The sucralose content in the fourth aqueous phase was 0.2g / L. The second ester phase is concentrated to dryness to recover butyl acetate. Pure water is added to assist desolventization during the concentration process. Finally, the obtained residue is diluted to 1000 mL with pure water to obtain a tetrachlorosucrose aqueous solution, wherein the tetrachlorosucrose content of the tetrachlorosucrose aqueous solution is 167.89 g / L and the butyl acetate content is 0.06 g / L.

[0076] (4) Alkaline hydrolysis step: 1000 mL of the tetrachlorosucrose aqueous solution obtained in step (3) was cooled to 10° C., and a 25 wt % tetrabutylammonium hydroxide aqueous solution was added dropwise. During the addition, the system temperature was controlled to be 10° C., and the addition was stopped when the pH value of the system was 12.5. The reaction was then kept warm for 1 hour. After the reaction was completed, the tetrachlorosucrose content in the product system was 0.3 g / L. 35 wt % hydrochloric acid was added dropwise to the product system until the pH value of the system was 6, to obtain 1472 mL of a crude sucralose aqueous solution. The crude sucralose aqueous solution is concentrated to dryness, methanol is added for azeotropy during the concentration process, and then the obtained residue is diluted to 7360 mL with methanol. At this time, tetrabutylammonium chloride is precipitated from the system and separated by suction filtration; the filtrate is concentrated to dryness, and methanol is recovered. Pure water is added for azeotropy with methanol during the concentration process to ensure low methanol residue. Finally, the obtained residue is diluted to 1472 mL with pure water to obtain a sucralose aqueous solution, wherein the methanol content of the sucralose aqueous solution is 0.2 g / L, the sucralose content is 95.99 g / L, and the sucralose yield is 60.8%.

[0077] Example 3

[0078] according to Figure 1 The process flow chart shown in the figure is used to prepare sucralose, and the specific steps are as follows:

[0079] (1) Dehydration step: 200 g of sucrose and 1000 mL of N,N-dimethylformamide (DMF) were added to a three-necked flask in sequence, and the mixture was heated to 70° C. to completely dissolve. The mixture was then evacuated to a vacuum degree of −0.1 MPa (instrument pressure) while maintaining the temperature at 70° C. to perform dehydration. When the water content in the condensed and collected DMF was 0.20 wt %, the dehydration was completed to obtain 796 mL of a sucrose constant solution, wherein the sucrose content in the sucrose constant solution was 251.01 g / L.

[0080] (2) Chlorination reaction step: add 1065 mL of trichloroethane to a three-necked flask, and drop 213 mL of thionyl chloride into the trichloroethane, and control the system temperature to be 5° C. during the dropwise addition; after the dropwise addition of thionyl chloride is completed, drop 796 mL of the sucrose constant volume solution obtained in step (1); after the dropwise addition of the sucrose constant volume solution is completed, heat the mixture to 20° C. and keep the mixture for 0.5 h, heat the mixture to 45° C. and keep the mixture for 0.5 h, heat the mixture to 85° C. and keep the mixture for 1 h, and heat the mixture to 110° C. and keep the mixture for 1.5 h; after the reaction is completed, cool the obtained product system to 5° C., drop 20 wt % ammonia water under stirring, adjust the pH value of the system to 11, and react for 0.5 h, then adjust the pH value of the obtained product system to 8 with 35 wt % hydrochloric acid, and obtain 2360 mL of chlorinated neutralization solution.

[0081] (3) Separation step: 2360 mL of the chlorinated neutralized solution obtained in step (2) was concentrated to dryness, DMF and trichloroethane were recovered, pure water was added to assist desolventization during the concentration process, and finally the residue was diluted to 1000 mL with pure water to obtain a first aqueous phase, in which the DMF content was 3.91 g / L and the trichloroethane content was 0.42 g / L. Under room temperature (25° C.), the first aqueous phase was extracted 4 times with butyl acetate, and the volume of butyl acetate used for each extraction was 2000 mL. During the extraction process, the ester phases obtained from the first two extractions were combined and recorded as the first ester phase, totaling 4193 mL. The ester phases obtained from the second two extractions were used in the butyl acetate extraction step of the first aqueous phase in the next batch of sucralose preparation process; the raffinate aqueous phase was recorded as the second aqueous phase, totaling 685 mL, and was treated as wastewater. The sucralose content in the second aqueous phase was 0.1 g / L. 4.19 g of activated carbon was added to the first ester phase for decolorization, and then the activated carbon was removed by filtration. The first ester phase after decolorization was washed with pure water gradient water 4 times, and the volume of pure water used for each washing was 630 mL, and 4157 mL of the second ester phase was obtained. During the pure water washing process, the aqueous phases obtained from the first two washings were combined and recorded as the third aqueous phase, a total of 1321 mL, and the aqueous phases obtained from the last two washings were used in the washing step of the first ester phase in the preparation process of the next batch of sucralose. The third aqueous phase was extracted once with 2642 mL of butyl acetate to obtain 2670 mL of butyl acetate phase, which was used for the next batch of extraction of the first aqueous phase. The residual aqueous phase was recorded as the fourth aqueous phase and treated as wastewater. The sucralose content in the fourth aqueous phase was 0.1 g / L. The second ester phase is concentrated to dryness to recover butyl acetate. Pure water is added during the concentration process to assist desolventization. Finally, the residue is diluted to 1000 mL with pure water to obtain a tetrachlorosucrose aqueous solution, wherein the tetrachlorosucrose content of the tetrachlorosucrose aqueous solution is 170.26 g / L and the butyl acetate content is 0.05 g / L.

[0082] (4) Alkaline hydrolysis step: 1000 mL of the tetrachlorosucrose aqueous solution obtained in step (3) was cooled to 5° C., and a 10 wt % tetramethylammonium hydroxide aqueous solution was added dropwise. During the addition, the system temperature was controlled to be 5° C. The addition was stopped when the pH value of the system was 10.5, and the reaction was then kept warm for 4 h. After the reaction, the tetrachlorosucrose content in the product system was 0.4 g / L. 35 wt % hydrochloric acid was added dropwise to the product system until the pH value of the system was 7, to obtain 1457 mL of a crude sucralose aqueous solution. The crude sucralose aqueous solution is concentrated to dryness, methanol is added for azeotropy during the concentration process, and then the obtained residue is diluted to 8742 mL with methanol. At this time, tetramethylammonium chloride is precipitated from the system and separated by suction filtration; the filtrate is concentrated to dryness, and methanol is recovered. Pure water is added for azeotropy with methanol during the concentration process to ensure low residual methanol. Finally, the obtained residue is diluted to 1457 mL with pure water to obtain a sucralose aqueous solution, wherein the methanol content of the sucralose aqueous solution is 0.1 g / L, the sucralose content is 100.50 g / L, and the sucralose yield is 63.0%.

[0083] The description of the above embodiments is only used to help understand the method of the present invention and its core idea. It should be noted that for those of ordinary skill in the art, without departing from the principles of the present invention, several improvements and modifications may be made to the present invention, and these improvements and modifications also fall within the scope of protection of the claims of the present invention. The various modifications to these embodiments are obvious to those skilled in the art, and the general principles defined herein may be implemented in other embodiments without departing from the spirit or scope of the present invention. Therefore, the present invention will not be limited to the embodiments shown herein, but will conform to the widest range consistent with the principles and novel features disclosed herein.

Claims

1. A method for preparing sucralose, characterized in that: The following steps are involved: Mixing sucrose, N,N-dimethylformamide, trichloroethane and thionyl chloride to perform a chlorination reaction to obtain a chlorinated product solution; adjusting the pH value of the chlorinated product solution to alkaline, performing a decomposition reaction to obtain tetrachlorosucrose; The sucralose, water and an alkaline hydrolysis agent are mixed to perform an alkaline hydrolysis reaction to obtain sucralose; the alkaline hydrolysis agent is a tetramethylammonium hydroxide aqueous solution, a tetraethylammonium hydroxide aqueous solution or a tetrabutylammonium hydroxide aqueous solution; and the concentration of the alkaline hydrolysis agent is 10 or 25 wt%.

2. The preparation method according to claim 1, characterized in that: The mixing of sucrose, N,N-dimethylformamide, trichloroethane and thionyl chloride comprises: mixing sucrose with N,N-dimethylformamide to obtain a sucrose constant volume solution; and sequentially dropping the thionyl chloride and the sucrose constant volume solution into the trichloroethane; The sucrose constant volume solution also includes a vacuum dehydration treatment before use, the vacuum dehydration treatment temperature is 50-70° C., and the vacuum degree is -0.1 MPa; the vacuum dehydration treatment ends when the water content in the condensed and collected N,N-dimethylformamide is less than 0.3wt%; The thionyl chloride and the sucrose constant volume solution are added dropwise at -5 to 5°C.

3. The preparation method according to claim 1, characterized in that: The dosage ratio of the sucrose to N,N-dimethylformamide is 1 g: (3-5) mL; the molar ratio of the sucrose to thionyl chloride is 1: (5-10); the volume ratio of the thionyl chloride to trichloroethane is 1: (4-5); The chlorination reaction comprises a first stage insulation reaction, a first heating, a second stage insulation reaction, a second heating, a third stage insulation reaction, a third heating and a fourth stage insulation reaction in sequence; the temperature of the first stage insulation reaction is 10-20°C, and the insulation time is 0.5-1h; the temperature of the second stage insulation reaction is 35-45°C, and the insulation time is 0.5-1h; the temperature of the third stage insulation reaction is 75-85°C, and the insulation time is 1-1.5h; the temperature of the fourth stage insulation reaction is 100-110°C, and the insulation time is 1.5-2h.

4. The preparation method according to claim 1, characterized in that: The pH value of the chlorinated product solution is adjusted to alkaline at 0-10°C; the alkalinity is pH=9-11; The reagent used to adjust the pH value of the chlorinated product solution is an inorganic alkali solution.

5. The preparation method according to claim 1, characterized in that: The temperature of the decomposition reaction is 0-10° C., and the insulation time is 0.5-1 h.

6. The preparation method according to any one of claims 1 and 4 to 5, characterized in that: The decomposition reaction also includes: The pH value of the decomposition product liquid obtained by the decomposition reaction is adjusted to 6 to 8 by using an inorganic acid to obtain a chlorinated neutralization liquid; The chlorinated neutralized liquid is separated and purified to obtain tetrachlorosucrose.

7. The preparation method according to claim 6, characterized in that: The separation and purification comprises: The chlorinated neutralized liquid is concentrated to dryness, and the residue is mixed with water to obtain a first aqueous phase; the content of N,N-dimethylformamide in the first aqueous phase is less than 5 g / L, and the content of trichloroethane is less than 1 g / L; The first aqueous phase is extracted with butyl acetate to obtain a first ester phase and a second aqueous phase; the number of extractions is 4 to 6 times, and the volume ratio of butyl acetate to the first aqueous phase used in each extraction is (0.5 to 2): 1; the extraction is based on the content of sucralose in the second aqueous phase being less than 0.5 g / L; The first ester phase is decolorized and washed with water in sequence to obtain a second ester phase and a third aqueous phase; the decolorization material is activated carbon, and the mass ratio of the activated carbon to the volume ratio of the first ester phase is (0.1-0.3) g:100 mL; the washing is performed 4-6 times, and the volume ratio of water used in each washing to the first ester phase is (0.1-0.2):1; the third aqueous phase is extracted with butyl acetate to obtain a butyl acetate phase and a fourth aqueous phase, and the butyl acetate phase is used to extract the next batch of the first aqueous phase; the third aqueous phase is extracted with butyl acetate 1-2 times, and the volume ratio of butyl acetate used in each extraction to the third aqueous phase is (0.5-2):1; the third aqueous phase is extracted with butyl acetate to make the content of sucralose in the fourth aqueous phase less than 0.5 g / L as a benchmark; The second ester phase is concentrated to dryness to obtain sucralose.

8. The preparation method according to claim 1, characterized in that: The conditions of the alkaline hydrolysis reaction include: pH value of 10.5-12.5, temperature of 0-10° C., and insulation time of 1-4 hours.

9. The preparation method according to claim 1, characterized in that: The alkaline hydrolysis reaction further comprises: The pH value of the alkaline hydrolysis product solution obtained by the alkaline hydrolysis reaction is adjusted to 6-8 by using hydrochloric acid to obtain a crude sucralose product aqueous solution; The crude sucralose aqueous solution is concentrated to dryness, the residue is dissolved in methanol, the chloride salt is precipitated, and then the solid-liquid separation is performed, the obtained filtrate is concentrated to dryness, and the residue is dissolved in water to obtain an aqueous solution containing sucralose; the volume of the methanol is 4 to 6 times the volume of the crude sucralose aqueous solution; the content of methanol in the aqueous solution containing sucralose is less than 0.3 g / L.

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