A method for preparing crude sucralose using an improved alcohol-water alkaline hydrolysis system

Abstract

This invention provides a method for preparing crude sucralose using an improved alcohol-water alkaline hydrolysis system, relating to the field of fine chemical technology. Using an aqueous solution of crude sucralose-6-acetate as raw material, the method involves alkaline hydrolysis in an alkali metal hydroxide and methanol-water system. This process converts sucralose-6-acetate and sucralose ester impurities (sucralose diester and tetrachlorosucralose-6-acetate) in the crude sucralose-6-acetate aqueous solution into sucralose, significantly improving the sucralose yield. The invention employs multiple concentrations and multiple extraction-back-extraction processes between the ethyl acetate / water dual solvent system to achieve equilibrium between fat-soluble and water-soluble impurities. This avoids caramelization of sugars during concentration, ensures sufficient crystallization of sucralose in ethyl acetate, improves the sucralose yield, effectively separates inorganic salts from sucralose, and reduces the cost of treating subsequent high-salinity wastewater.

Description

Technical Field

[0001] This invention relates to the field of fine chemical technology, and in particular to a method for preparing crude sucralose using an improved alcohol-water alkaline hydrolysis system. Background Technology

[0002] Sucralose, commonly known as sucralose, is a new generation of sweetener made from sucrose, and its sweetness is 600 times that of sucrose. Due to its pure taste, non-metabolism, high sweetness, zero calories, good stability, and high safety, it is considered the most valuable "zero-calorie" sugar of the 21st century and is widely used in food, beverage, daily chemical, and pharmaceutical fields.

[0003] In the existing technology, the production process of sucralose involves sequentially esterifying, chlorinating, alcoholyzing, crystallizing, and drying sucrose. The esterification stage mainly uses two processes: dibutyltin oxide and trimethyl orthoacetate. The chlorination stage mainly uses two chlorinating agents: phosgene and thionyl chloride. The alcoholyzing stage mainly uses the sodium methoxide / methanol process and the sodium hydroxide alkaline hydrolysis process.

[0004] Taking the alcoholysis section as an example, the current sodium methoxide / methanol production process uses sucralose-6-acetate as a raw material for transesterification. In production, this section requires sucralose-6-acetate to be purified before proceeding; otherwise, subsequent sucralose purification becomes difficult, affecting the sucralose yield. To address this issue, existing methods for preparing sucralose through alcoholysis of sucralose-6-acetate (e.g., Chinese patents CN104004032A, CN112805291A, CN1814609A, CN101012250A) all first purify the synthesized sucralose-6-acetate before alcoholysis. However, the sucralose yield in these methods is consistently below 86.8%, indicating a low yield. Summary of the Invention

[0005] In view of this, the purpose of this invention is to provide a method for preparing crude sucralose using an improved alcohol-water alkaline hydrolysis system, which results in a high sucralose yield.

[0006] To achieve the above-mentioned objectives, the present invention provides the following technical solution:

[0007] This invention provides a method for preparing crude sucralose using an improved alcohol-water alkaline hydrolysis system, comprising the following steps:

[0008] (1) The crude sucralose-6-acetate aqueous solution was extracted with ethyl acetate to obtain a first ethyl ester phase and a first aqueous phase, respectively; the first ethyl ester phase was concentrated to obtain a syrup; the syrup was dissolved in a methanol-water mixed solvent to obtain a sucralose-6-acetate methanol aqueous solution; the crude sucralose-6-acetate aqueous solution includes sucralose-6-acetate, sucralose diester and tetrachlorosucralose-6-acetate;

[0009] (2) The methanol aqueous solution of sucralose-6-acetate is mixed with an alkali metal hydroxide to carry out an alkaline hydrolysis reaction. The resulting reaction solution is neutralized to obtain a sucralose alkaline hydrolysate. The sucralose alkaline hydrolysate is concentrated to obtain a crude sucralose concentrate. The crude sucralose concentrate is dissolved in water to obtain a second aqueous phase.

[0010] (3) The second aqueous phase was extracted with ethyl acetate to obtain a second ethyl ester phase and a third aqueous phase, respectively;

[0011] (4) The second ethyl ester phase is washed with water to obtain the fourth aqueous phase and the third ethyl ester phase respectively; the fourth aqueous phase is reused in step (2) to dissolve the crude sucralose concentrate;

[0012] (5) The third ethyl ester phase is concentrated to obtain a third ethyl ester phase concentrate; the third ethyl ester phase concentrate is dissolved in ethyl acetate to obtain crude sucralose in ethyl acetate solution; the crude sucralose in ethyl acetate solution is crystallized to obtain crude sucralose and the fourth ethyl ester phase, respectively.

[0013] (6) The fourth ethyl ester phase is washed with water to obtain the fifth aqueous phase and the fifth ethyl ester phase respectively; the fifth aqueous phase is recycled in step (2) to dissolve the crude sucralose concentrate.

[0014] Preferably, in step (1), the residual amount of ethyl acetate in the syrup is <0.1 wt%.

[0015] Preferably, in step (1), the content of sucralose-6-acetate in the first aqueous phase is <0.5 g / L.

[0016] Preferably, in step (1), the concentration of methanol in the methanol-water mixed solvent is 10-60 wt%.

[0017] Preferably, in step (2), the pH value of the alkaline hydrolysis reaction is 11.5 to 12.5, the temperature is 0 to 20°C, and the time is 0.5 to 2 hours.

[0018] Preferably, in step (2), the methanol content in the crude sucralose concentrate is <0.1 wt%.

[0019] Preferably, in step (3), the ethyl acetate extraction is performed 5 to 7 times; the volume ratio of the second aqueous phase to the ethyl acetate used in a single extraction is 1:1 to 2.

[0020] The ethyl ester phases obtained from the first and second ethyl acetate extractions were combined as the second ethyl ester phase;

[0021] The ethyl ester phase obtained from the 3rd to 7th ethyl acetate extractions was used for the ethyl acetate extraction of the second aqueous phase in the next batch of crude sucralose preparation.

[0022] Preferably, in step (4), the number of water washes is 4 to 6; the volume ratio of the second ethyl ester phase to the water used in a single water wash is 1:0.1 to 0.15;

[0023] The aqueous phases obtained from the first and second water washes are combined as the fourth aqueous phase;

[0024] The aqueous phase obtained from the 3rd to 6th water washes is used for washing the second ethyl ester phase in the next batch of crude sucralose preparation.

[0025] Preferably, in step (4), the content of sucralose in the third aqueous phase is <0.5g / L.

[0026] Preferably, in step (5), the water content of the third ethyl ester phase concentrate is <0.5 wt%.

[0027] Preferably, in step (5), the sugar content of the crude sucralose ethyl acetate solution is 50-70 wt%.

[0028] Preferably, in step (5), the crystallization temperature is 30-50°C and the time is 6-12 hours.

[0029] Preferably, in step (6), the number of water washes is 3 to 4; the volume ratio of the fourth ethyl ester phase to the water used in a single water wash is 1:0.3 to 0.5.

[0030] The aqueous phases obtained from the first and second water washes are combined as the fifth aqueous phase;

[0031] The aqueous phase obtained from the 3rd and 4th water washes is used for the water wash of the fourth ethyl ester phase in the next batch of crude sucralose preparation.

[0032] Preferably, in step (6), the sucralose content in the fifth ethyl ester phase is <0.1 g / L.

[0033] This invention provides a method for preparing crude sucralose using an improved alcohol-water alkaline hydrolysis system. The invention uses an alkali metal hydroxide as the alkaline hydrolysis reagent, and the hydrolysis is carried out in a methanol-water system. Sucralose-6-acetate, sucralose diester, and sucralose-6-acetate are all hydrolyzed to generate the corresponding sucralose and tetrachlorosucralose. The tetrachlorosucralose further undergoes dechlorination to form sucralose, thus converting sucralose-6-acetate and impurities (sucralose diester and tetrachlorosucralose-6-acetate) in the first aqueous solution into sucralose. This significantly improves the raw material conversion rate and sucralose yield. Compared to methods using high-purity sucralose-6-acetate as a raw material for alkaline hydrolysis to prepare sucralose, the method provided by this invention significantly improves both the raw material conversion rate and sucralose yield. The use of a methanol-water system for alkaline hydrolysis improves the efficiency of the hydrolysis, reduces the precipitation of fat-soluble impurities during the cooling alkaline hydrolysis process, and minimizes uneven stirring and reduced mass transfer, thereby improving product yield. The method provided by this invention uses multiple concentrations and multiple extraction-back-extraction processes between the ethyl acetate / water dual solvent system to separate fat-soluble and water-soluble impurities, achieving equilibrium in the system and preventing caramelization of sugars during concentration. This allows sucralose to fully crystallize in ethyl acetate, increasing the sucralose yield. Inorganic salts (such as sodium chloride, potassium chloride, and ammonium chloride) are readily soluble in water but insoluble in ethyl acetate. The sucralose hydrolysate obtained after alkaline hydrolysis and pH adjustment to neutral contains a significant amount of inorganic salts. If ethyl acetate is used, sucralose can be extracted from the system by heating or at room temperature. However, this requires a large amount of ethyl acetate, and the high-salt wastewater remaining after extraction needs to be treated by evaporation and crystallization to collect the inorganic salts. The method provided by this invention utilizes the characteristic that inorganic salts (such as sodium chloride, potassium chloride, and ammonium chloride) are insoluble in ethyl acetate. It directly concentrates the sucralose alkaline hydrolysis solution to remove water and methanol solvent, and then adds ethyl acetate to dissolve it. Sucralose, water-soluble impurities, and fat-soluble impurities will dissolve in ethyl acetate, while inorganic salts are insoluble in ethyl acetate, thereby effectively separating inorganic salts from sucralose. Moreover, this invention reuses the fourth aqueous phase in step (2) to dissolve the crude sucralose concentrate, without having to reuse it before alkaline hydrolysis, reducing the volume of alkaline hydrolysis solution, lowering alkaline hydrolysis pressure, and reducing the amount of high COD wastewater. This reduces the treatment cost of subsequent high-salt and high-COD wastewater, alleviates subsequent environmental pressure, and has high industrial application value. Attached Figure Description

[0034] Figure 1 The process flow diagram for preparing crude sucralose using the improved alcohol-water alkaline hydrolysis system in Example 1 is shown. Detailed Implementation

[0035] The present invention will be further described below with reference to embodiments and accompanying drawings.

[0036] This invention provides a method for preparing crude sucralose using an improved alcohol-water alkaline hydrolysis system, comprising the following steps:

[0037] (1) The crude sucralose-6-acetate aqueous solution was extracted with ethyl acetate to obtain a first ethyl ester phase and a first aqueous phase, respectively; the first ethyl ester phase was concentrated to obtain a syrup; the syrup was dissolved in a methanol-water mixed solvent to obtain a sucralose-6-acetate methanol aqueous solution; the crude sucralose-6-acetate aqueous solution includes sucralose-6-acetate, sucralose diester and tetrachlorosucralose-6-acetate;

[0038] (2) The methanol aqueous solution of sucralose-6-acetate is mixed with an alkali metal hydroxide to carry out an alkaline hydrolysis reaction. The resulting reaction solution is neutralized to obtain a sucralose alkaline hydrolysate. The sucralose alkaline hydrolysate is concentrated to obtain a crude sucralose concentrate. The crude sucralose concentrate is dissolved in water to obtain a second aqueous phase.

[0039] (3) The second aqueous phase was extracted with ethyl acetate to obtain a second ethyl ester phase and a third aqueous phase, respectively;

[0040] (4) The second ethyl ester phase is washed with water to obtain the fourth aqueous phase and the third ethyl ester phase respectively; the fourth aqueous phase is reused in step (2) to dissolve the crude sucralose concentrate;

[0041] (5) The third ethyl ester phase is concentrated to obtain a third ethyl ester phase concentrate; the third ethyl ester phase concentrate is dissolved in ethyl acetate to obtain crude sucralose in ethyl acetate solution; the crude sucralose in ethyl acetate solution is crystallized to obtain crude sucralose and the fourth ethyl ester phase, respectively.

[0042] (6) The fourth ethyl ester phase is washed with water to obtain the fifth aqueous phase and the fifth ethyl ester phase respectively; the fifth aqueous phase is recycled in step (2) to dissolve the crude sucralose concentrate.

[0043] In this invention, unless otherwise specified, all raw material components are commercially available products well known to those skilled in the art.

[0044] In this invention, crude sucralose-6-acetate aqueous solution is extracted with ethyl acetate to obtain a first ethyl ester phase and a first aqueous phase; the first ethyl ester phase is concentrated to obtain a syrup; the syrup is dissolved in a methanol-water mixed solvent to obtain a sucralose-6-acetate methanol aqueous solution; the crude sucralose-6-acetate aqueous solution includes sucralose-6-acetate, sucralose diester, and tetrachlorosucralose-6-acetate.

[0045] In this invention, the content of sucralose-6-acetate in the raw material solution is preferably 50-80 g / L, more preferably 50-70 g / L; the mass ratio of sucralose-6-acetate, sucralose diester, and sucralose-6-acetate in the raw material solution is preferably 1:0.06-0.15:0.05-0.15, more preferably 1:0.08-0.1:0.06-0.1; the raw material solution preferably also includes NH4Cl and organic impurities, the concentration of NH4Cl is preferably 80-150 g / L, more preferably 85-120 g / L; the concentration of organic impurities is preferably 30-80 g / L, more preferably 30-50 g / L.

[0046] The present invention does not specifically limit the preparation method of the crude sucralose-6-acetate aqueous solution (denoted as the first aqueous solution). The crude sucralose-6-acetate aqueous solution of the above components can be obtained by using a preparation method well known to those skilled in the art that uses sucrose as the initial raw material to prepare crude sucralose-6-acetate. Specifically, for example: using sucrose as the raw material, N,N-dimethylformamide (DMF) as the solvent, organotin as the catalyst, and acetic anhydride as the acylating agent, a solution containing sucralose-6-acetate is prepared; then the obtained solution containing sucralose-6-acetate is successively subjected to chlorination (thionyl chloride), neutralization with ammonia water, vacuum concentration to dryness, and dissolution with water to obtain the crude sucralose-6-acetate aqueous solution.

[0047] In this invention, the preferred temperature for ethyl acetate extraction is 40–60°C, more preferably 45–55°C, and even more preferably 50°C. The invention does not specifically limit the number of ethyl acetate extractions, but the content of sucralose-6-acetate in the aqueous phase obtained from the last ethyl acetate extraction (i.e., the first aqueous phase) is <0.5 g / L, specifically 4–8 times. The preferred extraction time for each ethyl acetate extraction is 10–30 min, more preferably 15–25 min. The preferred volume ratio of the crude sucralose-6-acetate aqueous solution to the ethyl acetate used for the single ethyl acetate extraction is 1:0.2–0.6, more preferably 1:0.4–0.5. In this invention, the first aqueous phase is preferably treated with high-salinity wastewater.

[0048] This invention does not specifically limit the concentration method; any concentration method well-known to those skilled in the art can be used, such as vacuum concentration. The preferred concentration temperature is 60–80°C, and the preferred vacuum degree is -0.1–-0.08 MPa (gauge pressure). This invention does not specifically limit the concentration time; concentration is sufficient until the residual amount of ethyl acetate in the syrup is <0.1 wt%. By controlling the residual amount of ethyl acetate in the syrup, this invention can avoid the formation of byproducts such as acetic acid and ethanol from ethyl acetate in subsequent alkaline hydrolysis steps, further improving the purity and yield of sucralose.

[0049] In this invention, the concentration of methanol in the methanol-water mixed solvent is preferably 10-60 wt%, more preferably 20-50 wt%. In this invention, the concentration of sucralose-6-acetate in the sucralose-6-acetate methanol-water solution is preferably 50-100 g / L, more preferably 50-80 g / L.

[0050] After obtaining a methanol-water solution of sucralose-6-acetate, the present invention mixes the methanol-water solution of sucralose-6-acetate with an alkali metal hydroxide to carry out an alkaline hydrolysis reaction, neutralizes the resulting reaction solution to obtain a sucralose alkaline hydrolysate; concentrates the sucralose alkaline hydrolysate to obtain a crude sucralose concentrate, and dissolves the crude sucralose concentrate in water to obtain a second aqueous phase.

[0051] In this invention, the alkali metal hydroxide preferably includes sodium hydroxide and / or potassium hydroxide, more preferably sodium hydroxide; the alkali metal hydroxide is preferably used in the form of an aqueous solution of alkali metal hydroxide, and the concentration of the aqueous solution of alkali metal hydroxide is preferably 10-40 wt%, more preferably 20-35 wt%; this invention does not have a special limitation on the amount of alkali metal hydroxide used, as long as the pH value of the alkaline hydrolysis reaction is maintained at 11.5-12.5, more preferably 11.8-12.5, and even more preferably 12-12.3; the temperature of the alkaline hydrolysis reaction is preferably 0-20°C, more preferably 5-15°C, and even more preferably 5-10°C; the time of the alkaline hydrolysis reaction is preferably 0.5-2 h, more preferably 1-1.5 h. This invention performs an alkaline hydrolysis reaction under the aforementioned conditions. Sucralose diester undergoes hydrolysis to produce sucralose, and sucralose-6-acetate undergoes dechlorination and hydrolysis to produce sucralose. Furthermore, it avoids the generation of byproducts due to excessively high pH or temperature during the alkaline hydrolysis reaction. The alkaline hydrolysis is carried out in a methanol-water system, which increases the solubility of fat-soluble impurities in the aqueous system at low temperatures, thereby improving the alkaline hydrolysis efficiency. Moreover, this invention uses alkali metal hydroxides as the alkaline hydrolysis reagent in a methanol-water system. Compared to the traditional sodium methoxide / methanol reaction system, which carries out alkaline hydrolysis with higher risks, it eliminates the need for high-purity alkaline sucralose-6-acetate, omitting the purification step of sucralose-6-acetate, significantly shortening the process and reducing production costs.

[0052] In this invention, the acid used for neutralization preferably includes hydrochloric acid; the concentration of the acid is preferably 15-35 wt%, more preferably 20-30 wt%. This invention does not have a particular limitation on the amount of acid used, as long as it can neutralize the system to a pH of 6.8-7.

[0053] The present invention does not have a particular limitation on the concentration method, and any concentration method known to those skilled in the art can be used, such as vacuum concentration. The concentration temperature is preferably 60 to 80°C, and the vacuum degree is preferably -0.1 to -0.08 MPa (gauge pressure). The present invention does not have a particular limitation on the concentration time, and the concentration can be carried out until the methanol content in the crude sucralose concentrate is <0.1 wt%.

[0054] In this invention, the volume ratio of the sucralose-6-acetate methanol aqueous solution to water is preferably 1:0.5 to 1, more preferably 1:0.6 to 0.9.

[0055] After obtaining the second aqueous phase, the present invention extracts the second aqueous phase with ethyl acetate to obtain the second ethyl ester phase and the third aqueous phase, respectively.

[0056] In this invention, the ethyl acetate extraction is preferably performed 5 to 7 times; the volume ratio of the second aqueous phase to the ethyl acetate used in a single ethyl acetate extraction is preferably 1:1 to 2, more preferably 1:1.5; preferably, the ethyl ester phases obtained from the first and second ethyl acetate extractions are combined as the second ethyl ester phase; preferably, the ethyl ester phases obtained from the third to seventh ethyl acetate extractions are used for the ethyl acetate extraction of the second aqueous phase in the next batch of crude sucralose preparation. Specifically, the ethyl ester phase obtained from the third ethyl acetate extraction is used for the first ethyl acetate extraction of the second aqueous phase in the next batch of crude sucralose preparation, and the ethyl ester phase obtained from the fourth ethyl acetate extraction is used for the second ethyl acetate extraction in the next batch of crude sucralose preparation. The ethyl ester phase obtained from the second and fifth ethyl ester extractions of the aqueous phase is used for the third ethyl ester extraction of the second aqueous phase in the next batch of crude sucrose preparation. The ethyl ester phase obtained from the sixth ethyl ester extraction is used for the fourth ethyl ester extraction of the second aqueous phase in the next batch of crude sucrose preparation. The ethyl ester phase obtained from the seventh ethyl ester extraction is used for the fifth ethyl ester extraction of the second aqueous phase in the next batch (i.e., the ethyl ester phases obtained from the third to seventh ethyl ester extractions are used sequentially for the first to fifth ethyl ester extractions of the second aqueous phase in the next batch of crude sucralose preparation). The sixth and seventh ethyl ester extractions of the second aqueous phase in the next batch of crude sucralose preparation are preferably performed using pure ethyl acetate.

[0057] After obtaining the second ethyl ester phase, the present invention washes the second ethyl ester phase with water to obtain the fourth aqueous phase and the third ethyl ester phase respectively; the fourth aqueous phase is reused in step (2) to dissolve the crude sucralose concentrate.

[0058] In this invention, the number of water washes is preferably 4 to 6; the volume ratio of the second ethyl ester phase to the water used in a single wash is preferably 1:0.1 to 0.15, more preferably 1:0.11 to 0.14, and even more preferably 1:0.12 to 0.13; preferably, the aqueous phases obtained from the first and second water washes are combined as the fourth aqueous phase; the aqueous phases obtained from the third to sixth water washes are preferably used for the water wash of the second ethyl ester phase in the next batch of crude sucralose preparation process. Specifically, the aqueous phase obtained from the third water wash is used for the first water wash of the second ethyl ester phase in the next batch of crude sucralose preparation process, and the aqueous phase obtained from the fourth water wash is used for... The aqueous phase obtained from the second and fifth water washes of the second ethyl ester phase in the next batch of crude sucralose preparation is used for the third water wash of the second ethyl ester phase in the next batch of crude sucralose preparation; the aqueous phase obtained from the sixth water wash is used for the fourth water wash of the second ethyl ester phase in the next batch of crude sucralose preparation; and the aqueous phase obtained from the seventh water wash is used for the fifth water wash of the second ethyl ester phase in the next batch of crude sucralose preparation (i.e., the aqueous phases obtained from the third to seventh water washes are used sequentially for the first to fifth water washes of the second ethyl ester phase in the next batch of crude sucralose preparation). The sixth and seventh water washes of the second ethyl ester phase in the next batch of crude sucralose preparation are preferably performed using pure water.

[0059] In this invention, the content of sucralose in the third aqueous phase is preferably <0.5 g / L.

[0060] After obtaining the third ethyl ester phase, the present invention concentrates the third ethyl ester phase to obtain a third ethyl ester phase concentrate; dissolves the third ethyl ester phase concentrate in ethyl acetate to obtain crude sucralose in ethyl acetate solution; and crystallizes the crude sucralose in ethyl acetate solution to obtain crude sucralose and the fourth ethyl ester phase, respectively.

[0061] The present invention does not have a particular limitation on the concentration method, and any concentration method known to those skilled in the art can be used, such as vacuum concentration. The concentration temperature is preferably 60 to 80°C, and the vacuum degree is preferably -0.1 to -0.08 MPa (gauge pressure). The present invention does not have a particular limitation on the concentration time, and the concentration can be carried out until the water content of the third ethyl ester phase concentrate is <0.5 wt%.

[0062] The present invention does not have a particular limitation on the amount of ethyl acetate used, but the sugar content (Bx) of the crude sucralose ethyl acetate solution is 50-70 wt%, more preferably 55-65 wt%, and even more preferably 60 wt%.

[0063] In this invention, the crystallization temperature is preferably 30-50°C, more preferably 35-45°C, and even more preferably 40°C; the crystallization time is preferably 6-12 hours, more preferably 7-11 hours, and even more preferably 8-10 hours.

[0064] After the crystallization is completed, the present invention preferably further includes solid-liquid separation to obtain crude sucralose and a fourth ethyl ester phase, respectively. In the present invention, the solid-liquid separation preferably includes filtration or vacuum filtration.

[0065] After obtaining the fourth ethyl ester phase, the present invention washes the fourth ethyl ester phase with water to obtain the fifth aqueous phase and the fifth ethyl ester phase respectively; the fifth aqueous phase is preferably reused in step (2) to dissolve the crude sucralose concentrate. In this invention, the number of water washings is preferably 3 to 4 times; the volume ratio of the fourth ethyl ester phase to the water used in a single water washing is preferably 1:0.3 to 0.5, more preferably 1:0.35 to 0.45, and even more preferably 1:0.4; this invention preferably combines the aqueous phases obtained from the first and second water washings as the fifth aqueous phase; preferably, the aqueous phases obtained from the third and fourth water washings are used for the water washing of the second ethyl ester phase in the next batch of crude sucralose preparation process. Specifically, the aqueous phase obtained from the third water washing is used for the first water washing of the second ethyl ester phase in the next batch of crude sucralose preparation process, and the aqueous phase obtained from the fourth water washing is used for the second water washing of the second ethyl ester phase in the next batch of crude sucralose preparation process (i.e., the aqueous phases obtained from the third and fourth water washings are used sequentially for the first and second water washings of the second ethyl ester phase in the next batch of crude sucralose preparation process). At this time, the third and fourth water washings of the second ethyl ester phase in the next batch of crude sucralose preparation process are preferably performed using pure water. In this invention, the fifth ethyl ester phase is preferably concentrated to obtain recovered ethyl acetate and sugar residue; the sugar residue is preferably treated as solid waste. In this invention, the sucralose content in the fifth ethyl ester phase is preferably <0.1 g / L. In this invention, the sugar residue is preferably treated as solid waste.

[0066] Both water-soluble and fat-soluble impurities are produced during a series of reactions involving sucrose, and therefore share a similar main structure with sucralose. This results in a certain degree of miscibility between the water-soluble impurities, fat-soluble impurities, and sucralose. This invention utilizes this relationship by selecting water and ethyl acetate as solvents to remove both water-soluble and fat-soluble impurities. Both solvents can dissolve and entrain sucralose, enabling its exchange between the two solvents. The sucralose is then enriched in ethyl acetate and crystallized to obtain crude sucralose.

[0067] The technical solutions of this invention will be clearly and completely described below with reference to the embodiments thereof. Obviously, the described embodiments are only a part of the embodiments of this invention, and not all of them. All other embodiments obtained by those skilled in the art based on the embodiments of this invention without creative effort are within the scope of protection of this invention.

[0068] In the following examples, the content of each substance was determined by high performance liquid chromatography (HPLC) under the following conditions using the external standard method. The analytical conditions for HPLC were as follows: Shimadzu HPLC system equipped with RID-10A differential refractive index detector, LC-10ADVP high-pressure pump, and CTO-10ASVP incubator; chromatographic column: Agilent XDB C18 column (250mm × 4.6mm, 5μm); mobile phase: methanol-0.125wt% dipotassium hydrogen phosphate aqueous solution (4:6, v / v); column temperature: 40℃; mobile phase flow rate: 1.0mL / min; wherein, methanol (chromatographic grade), dipotassium hydrogen phosphate (analytical grade), and water were ultrapure water.

[0069] The preparation method of the crude sucralose-6-acetate aqueous solution (denoted as the first aqueous solution, the composition of which is shown in Table 1) used in the following examples is as follows: using sucrose as raw material, DMF as solvent, organotin as catalyst, and acetic anhydride as acylating agent, a solution containing sucralose-6-acetate is prepared; the sucralose-6-acetate solution is subjected to chlorination, ammonia neutralization, vacuum concentration to dryness, and water dissolution in sequence to obtain the crude sucralose-6-acetate aqueous solution.

[0070] Table 1 Composition of the first aqueous solution

[0071] Components content Sucralose-6-acetate 55.2g / L Sucralose diester 5.4g / L Sucralose-6-acetate 4.0g / L <![CDATA[NH4Cl]]> 88.9g / L Other organic impurities 33.2g / L water 84.1 wt%

[0072] Example 1

[0073] use Figure 1 The process flow diagram shown illustrates the preparation of crude sucralose. The specific steps are as follows:

[0074] (1) Heat 1000 mL of the first aqueous solution and extract it repeatedly 4 times with ethyl acetate (500 mL per extraction) at 45 °C. After extraction, the ester phases are combined as the first ethyl ester phase and the aqueous phases are combined as the first aqueous phase. The content of sucralose-6-acetate in the first aqueous phase is 0.08 g / L. The first aqueous phase is treated as high-salt wastewater. The first ethyl ester phase is concentrated to dryness under vacuum (abbreviated as concentrated dry). 50 wt% methanol aqueous solution is added to the obtained syrup (ethyl acetate content < 0.5 g / L) to dissolve it. The 50 wt% methanol aqueous solution is then brought to a final volume of 800 mL to obtain sucralose-6-acetate methanol aqueous solution.

[0075] (2) Cool the methanol-water solution of sucralose-6-acetate to 7°C, then add 32wt% sodium hydroxide solution dropwise, and perform alkaline hydrolysis reaction at 7°C and pH 12.5 for 1 h. At the end of the reaction, the content of sucralose-6-acetate is 0.4 g / L. Then add 30wt% dilute hydrochloric acid dropwise to neutralize to pH 7. Concentrate the obtained sucralose alkaline hydrolysis solution to dryness, and add water (volume ratio of sucralose-6-acetate methanol-water solution to water = 1:0.7) to the obtained crude sucralose concentrate (methanol content is 0.09wt%) to dissolve it, and obtain the second aqueous phase.

[0076] (3) Ethyl acetate is added to the second aqueous phase for extraction 5 times (the volume ratio of the second aqueous phase to the ethyl acetate used for each extraction is 1:2). The ester phases obtained from the first and second extractions are combined to form the second ethyl ester phase. All aqueous phases are combined to form the third aqueous phase, which is then treated as high-salt wastewater. The ethyl ester phases obtained from the third to fifth ethyl acetate extractions are used sequentially for the first to third ethyl acetate extractions of the second aqueous phase in the next batch of crude sucralose preparation. At this time, the fourth to fifth ethyl acetate extractions of the second aqueous phase in the next batch of crude sucralose preparation are carried out using pure ethyl acetate.

[0077] (4) The second ethyl ester phase is washed with water 4 times (the volume ratio of the second ethyl ester phase to the water used for each wash is 1:0.1) to separate the phases into a third ethyl ester phase and a fourth aqueous phase. The aqueous phase obtained from the first and second washes is used as the fourth aqueous phase and is used in step (2) of the preparation of the next batch of crude sucralose to dissolve the crude sucralose concentrate. The aqueous phase obtained from the third and fourth washes is used in the first and second washes of the second ethyl ester phase in the preparation of the next batch of crude sucralose.

[0078] (5) The third ethyl ester phase was concentrated to remove water and part of ethyl acetate. Ethyl acetate was added to the obtained third ethyl ester phase concentrate (water content was 0.3 wt%) to adjust the sugar content Bx to 55 wt%. Then, it was crystallized at 45 °C for 8 h and filtered to obtain crude sucralose and the fourth ethyl ester phase, respectively.

[0079] (6) Add pure water (volume ratio of fourth ethyl ester phase to pure water = 1:0.5) to the fourth ethyl ester phase to wash away the residual sugar until the sucralose content is 0.08 g / L, and obtain the fifth aqueous phase and the fifth ethyl ester phase respectively. The fifth aqueous phase is used in step (2) of the preparation of the next batch of crude sucralose to dissolve the crude sucralose concentrate; the fifth ethyl ester phase is vacuum concentrated to dryness to obtain recovered ethyl acetate and sugar residue, and the sugar residue is treated as solid waste;

[0080] (7) Following the operations of steps (1) to (5) (recorded as 0 recycling times), the fourth aqueous phase, fifth aqueous phase, sixth aqueous phase, sixth ester phase, and seventh ethyl ester phase are recycled 17 times. In step (3), the phrase "add water (volume ratio of sucralose-6-acetic acid methanol aqueous solution to water = 1:0.7) to the obtained crude sucralose concentrate (water content 0.1 wt%) to dissolve" is replaced with "add the fourth aqueous phase and the fifth aqueous phase to the obtained crude sucralose concentrate to dissolve". In step (3), the first to third ethyl acetate extractions of the second aqueous phase were performed using the ethyl ester phase obtained from the third to fifth ethyl acetate extractions of the second aqueous phase in step (3) of the previous batch of crude sucralose preparation. The fourth to fifth ethyl acetate extractions of the second aqueous phase were performed using pure ethyl acetate. In step (4), the first to second water washes of the second ethyl ester phase were performed using the aqueous phase obtained from the third to fourth water washes of the second ethyl ester phase in step (4) of the previous batch of crude sucralose preparation. The third to fourth water washes of the second ethyl ester phase were performed using pure water. The quality, purity, and yield of the crude sucralose obtained after 17 cycles of repeated cycles are shown in Table 2.

[0081] Table 2 Purity and Yield of Crude Sucralose

[0082]

[0083] Note: Yield is calculated by dividing the final mass of sucralose by the percentage of sucralose-6-acetate completely converted to sucralose. Both sucralose diester and sucralose-6-acetate can be converted to sucralose via alkaline hydrolysis, resulting in actual yields exceeding 100%. The theoretical maximum yield in Example 1 is 117.17%.

[0084] During the application process, the following conditions must be met: the content of sucralose-6-acetic acid in the first aqueous phase < 0.5 g / L, the content of sucralose in the third aqueous phase < 0.5 g / L, and the content of sucralose in the fifth ethyl ester phase < 0.1 g / L. If these conditions are not met, an additional extraction with ethyl acetate or washing with pure water is required to avoid loss of the target compound. During the concentration process of the third ethyl ester phase, the water content in the system must be < 0.5 wt%, and only fresh ethyl acetate can be used to remove water; using other dehydrating agents will affect the subsequent solvent separation. When the water content of the third ethyl ester phase concentrate exceeds 0.5 wt%, it will severely affect the crystallization of sucralose in the ethyl acetate phase.

[0085] During the recycling process, sucralose and impurities are in equilibrium in the ethyl ester phase, meaning the recycling continues until the sucralose yield is above 105%. The system employed in this invention is characterized by: benefiting from the conversion between sucralose diester and sucralose-6-acetate, a sucralose yield of over 110% can be achieved (based on the conversion of sucralose-6-acetate to sucralose); the mutual washing and recycling of the ester and aqueous phases minimizes losses caused by sucralose residue in sugar residue and wastewater. Furthermore, the presence of residual sucralose in the fourth and fifth aqueous phases further improves the sucralose yield.

[0086] As can be seen from the above examples, in the initial few operation processes, such as the first to third cycle, the yield is low because the ethyl acetate and water circulating in the system contain a low amount of components that can be converted into sucralose. After four cycles, if the yield is calculated based on the complete conversion of sucralose-6-acetate to sucralose, the yield will exceed 100%. This is because the crude sucralose-6-acetate aqueous solution also contains other components that can be converted into sucralose (sucralose diester and tetrachlorosucralose-6-acetate). The method provided by this invention can convert sucralose diester and tetrachlorosucralose-6-acetate into sucralose, thereby significantly improving the yield of sucralose. Compared with the method of preparing sucralose by alkaline hydrolysis using high-purity sucralose-6-acetate as raw material, the method provided by this invention significantly improves the yield of sucralose. Furthermore, this invention uses the crude sucralose-6-acetate aqueous solution as raw material, eliminating the need for purification, making the process simpler and avoiding the loss of sucralose-6-acetate caused by the purification required before alkaline hydrolysis in traditional processes.

[0087] Furthermore, this invention separates inorganic salts from the system before performing ethyl acetate / water dual-solvent extraction-back-extraction, reducing the difficulty of subsequent high-salt wastewater treatment. Sucralose has low solubility in ethyl acetate, but this invention introduces fat-soluble caramel impurities into ethyl acetate during the recycling of the fourth ethyl ester phase and the fourth aqueous phase, significantly increasing the solubility of sucralose in ethyl acetate. The extraction, washing, and recycling process balances the impurities in the system, allowing sucralose to accumulate and crystallize in ethyl acetate. By increasing the number of ethyl acetate / water dual-solvent extraction-back-extraction cycles, the need for subsequent sucralose-containing mother liquor / wash water to be returned to the concentration step for recovery is avoided. In addition, in the crystallization mother liquor, due to the ethyl acetate solvent system, there are many fat-soluble impurities. Since sucralose has high solubility in water, multiple washings can recover and reuse the uncrystallized sucralose while removing fat-soluble impurities. Through these methods, the yield of sucralose can be significantly improved. Therefore, compared with the method of preparing sucralose by alkaline hydrolysis using high-purity sucralose-6-acetate as a raw material, the method provided by the present invention has extremely obvious advantages.

[0088] In summary, the method provided by this invention employs alkaline hydrolysis in an alkali metal hydroxide and methanol-water system, followed by extraction and impurity removal using an ethyl acetate / water dual system. This method converts sucralose-6-acetate, sucralose diester, and tetrachlorosucralose-6-acetate into sucralose, which is then fully enriched and crystallized in the ethyl acetate phase. This avoids the losses caused by the purification process required before alkaline hydrolysis of sucralose-6-acetate in traditional processes, as well as the loss of some useful impurities, significantly improving the sucralose yield. Furthermore, the inorganic salts are discharged as a high-salt solution, rather than as solids, achieving the same efficiency in obtaining crude sucralose. Moreover, the aqueous phases (fourth and fifth aqueous phases) containing sucralose produced in the later stages can be used as solvents to dissolve the crude sucralose concentrate, enabling the reuse of the aqueous phase and creating greater value. This method has significant industrial application potential.

[0089] The above description of the embodiments is merely for the purpose of helping to understand the method and core ideas of the present invention. It should be noted that those skilled in the art can make various improvements and modifications to the present invention without departing from its principles, and these improvements and modifications also fall within the protection scope of the claims. Various modifications to these embodiments will be readily apparent to those skilled in the art, and the general principles defined herein can be implemented in other embodiments without departing from the spirit or scope of the invention. Therefore, the present invention is not to be limited to the embodiments shown herein, but is to be accorded the widest scope consistent with the principles and novel features disclosed herein.

Claims

1. A method for preparing crude sucralose using an improved alcohol-water alkaline hydrolysis system, characterized in that, Includes the following steps: (1) The crude sucralose-6-acetate aqueous solution was extracted with ethyl acetate to obtain a first ethyl ester phase and a first aqueous phase; the first ethyl ester phase was concentrated to obtain a syrup; the syrup was dissolved in a methanol-water mixed solvent to obtain a sucralose-6-acetate methanol-water solution; the crude sucralose-6-acetate aqueous solution included sucralose-6-acetate, sucralose diester and tetrachlorosucralose-6-acetate; the residual amount of ethyl acetate in the syrup was <0.1 wt%; the concentration of methanol in the methanol-water mixed solvent was 10~60 wt%; (2) The sucralose-6-acetate methanol aqueous solution is mixed with an alkali metal hydroxide to carry out an alkaline hydrolysis reaction. The resulting reaction solution is neutralized to obtain a sucralose alkaline hydrolysate. The sucralose alkaline hydrolysate is concentrated to obtain a crude sucralose concentrate. The crude sucralose concentrate is dissolved in water to obtain a second aqueous phase. The pH value of the alkaline hydrolysis reaction is 11.5~12.5, the temperature is 0~20℃, and the time is 0.5~2h. The methanol content in the crude sucralose concentrate is <0.1wt%. (3) The second aqueous phase was extracted with ethyl acetate to obtain a second ethyl ester phase and a third aqueous phase, respectively; (4) The second ethyl ester phase is washed with water to obtain the fourth aqueous phase and the third ethyl ester phase respectively; the fourth aqueous phase is reused in step (2) to dissolve the crude sucralose concentrate; (5) The third ethyl ester phase is concentrated to obtain a third ethyl ester phase concentrate; The third ethyl ester phase concentrate was dissolved in ethyl acetate to obtain crude sucralose in ethyl acetate solution; The crude sucralose ethyl acetate solution was crystallized to obtain crude sucralose and a fourth ethyl ester phase; the water content of the concentrated third ethyl ester phase solution was <0.5 wt%; the sugar content of the crude sucralose ethyl acetate solution was 50-70 wt%. (6) The fourth ethyl ester phase is washed with water to obtain the fifth aqueous phase and the fifth ethyl ester phase respectively; the fifth aqueous phase is recycled in step (2) to dissolve the crude sucralose concentrate; The fourth and fifth aqueous phases are recycled until the sucralose yield is above 105%.

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

3. The method according to claim 1, characterized in that, In step (3), the ethyl acetate extraction is performed 5 to 7 times; the volume ratio of the second aqueous phase to the ethyl acetate used in a single extraction is 1:1 to 2. The ethyl ester phases obtained from the first and second ethyl acetate extractions were combined as the second ethyl ester phase; The ethyl acetate phase obtained from the 3rd to 7th ethyl acetate extractions was used for the ethyl acetate extraction of the second aqueous phase in the next batch of crude sucralose preparation.

4. The method according to claim 1, characterized in that, In step (4), the number of water washes is 4 to 6; the volume ratio of the second ethyl ester phase to the water used in a single water wash is 1:0.1 to 0.15; The aqueous phases obtained from the first and second water washes are combined as the fourth aqueous phase; The aqueous phase obtained from the 3rd to 6th water washes is used for the water washing of the second ethyl ester phase in the next batch of crude sucralose preparation.

5. The method according to claim 1 or 4, characterized in that, In step (4), the content of sucralose in the third aqueous phase is <0.5g / L.

6. The method according to claim 1, characterized in that, In step (5), the crystallization temperature is 30~50℃ and the time is 6~12h.

7. The method according to claim 1, characterized in that, In step (6), the number of water washes is 3 to 4; the volume ratio of the fourth ethyl ester phase to the water used in a single water wash is 1:0.3 to 0.5; The aqueous phases obtained from the first and second water washes are combined as the fifth aqueous phase; The aqueous phase obtained from the 3rd and 4th water washes is used for the water wash of the fourth ethyl ester phase in the next batch of crude sucralose preparation.

8. The method according to claim 1, characterized in that, In step (6), the sucralose content in the fifth ethyl ester phase is <0.1 g / L.

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