WO2024082157A1 - Method for preparing crude sucralose using improved alcohol-water alkaline hydrolysis system - Google Patents

Abstract

The present invention relates to the technical field of fine chemical engineering, and provides a method for preparing a crude sucralose by using an alcohol-water alkaline hydrolysis system. According to the present invention, a sucralose-6-acetate crude aqueous solution is used as a raw material, and alkaline hydrolysis is performed in an alkali metal hydroxide and methanol water system, so that sucralose-6-acetate in the sucralose-6-acetate crude aqueous solution and chlorosucrose ester impurities (sucralose diester and tetrachlorosucrose-6-acetate) can be converted into sucralose, thereby remarkably increasing the yield of sucralose. According to the present invention, multiple times of concentration and multiple times of extraction-back extraction between ethyl acetate/water double-solvent system are used for separation, so that fat-soluble impurities and water-soluble impurities are balanced in a system, the phenomenon of saccharides coking in the concentration process can be avoided, sucralose is fully crystallized in ethyl acetate, the yield of sucralose is increased, the inorganic salt is effectively separated from sucralose, and the treatment cost of subsequent high-salinity wastewater is reduced.

Description

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

The invention relates to the technical field of fine chemical industry, and in particular to a method for preparing crude sucralose by utilizing an improved alcohol-water alkaline hydrolysis system.

Background technique

Sucralose, commonly known as sucralose, is a new generation of sweeteners made from sucrose, and its sweetness is 600 times that of sucrose. It is considered to be the most valuable "zero-calorie" sugar in the 21st century due to its pure taste, non-metabolism, high sweetness, no calories, good stability and high safety. It is widely used in many fields such as food, beverages, daily chemicals and medicine.

In the prior art, the production process of sucralose is to sequentially esterify, chlorinate, alcoholyze, crystallize and bake sucrose. The esterification process mainly uses two processes, dibutyltin oxide and trimethyl orthoacetate; the chlorination process mainly uses two chlorination reagents, phosgene and thionyl chloride; and the alcoholysis process mainly uses sodium methoxide/methanol process and sodium hydroxide alkaline hydrolysis process.

Taking the alcoholysis section as an example, the current sodium methoxide/methanol production process is an ester exchange reaction using sucralose-6-acetate as raw material. In production, this section requires that sucralose-6-acetate must be purified before it can be carried out, otherwise the subsequent purification of sucralose will become more difficult, affecting the yield of sucralose. In order to solve the above problems, the existing methods for preparing sucralose by alcoholysis of sucralose-6-acetate, such as Chinese patents CN104004032A, CN112805291A, CN1814609A, CN101012250A), first purify the synthesized sucralose-6-ethyl ester and then perform alcoholysis. However, the yield of sucralose in the above preparation methods is less than 86.8%, and the yield of sucralose is low.

Summary of the invention

In view of this, an object of the present invention is to provide a method for preparing crude sucralose using an improved alcohol-water alkaline hydrolysis system. The method provided by the present invention has a high sucralose yield.

In order to achieve the above-mentioned invention object, the present invention provides the following technical solutions:

The present invention provides a method for preparing crude sucralose by using an improved alcohol-water alkaline hydrolysis system, comprising the following steps:

(1) extracting a crude aqueous solution of sucralose-6-acetate with ethyl acetate to obtain a first ethyl ester phase and a first aqueous phase; concentrating the first ethyl ester phase to obtain a syrup; dissolving the syrup in a methanol-water mixed solvent to obtain a sucralose-6-acetate methanol aqueous solution; the crude aqueous solution of sucralose-6-acetate includes sucralose-6-acetate, sucralose diester and tetrachlorosucrose-6-acetate;

(2) mixing the sucralose-6-acetate methanol aqueous solution with an alkali metal hydroxide to perform an alkaline hydrolysis reaction, neutralizing the obtained reaction solution to obtain a sucralose alkaline hydrolyzate; concentrating the sucralose alkaline hydrolyzate to obtain a crude sucralose concentrate, and dissolving the crude sucralose concentrate in water to obtain a second aqueous phase;

(3) extracting the second aqueous phase with ethyl acetate to obtain a second ethyl ester phase and a third aqueous phase;

(4) washing the second ethyl ester phase with water to obtain a fourth aqueous phase and a third ethyl ester phase, respectively; the fourth aqueous phase is reused in step (2) to dissolve the crude sucralose concentrate;

(5) concentrating the third ethyl ester phase to obtain a third ethyl ester phase concentrate; dissolving the third ethyl ester phase concentrate in ethyl acetate to obtain a crude sucralose ethyl acetate solution; crystallizing the crude sucralose ethyl acetate solution to obtain crude sucralose and a fourth ethyl ester phase, respectively;

(6) washing the fourth ethyl ester phase with water to obtain a fifth aqueous phase and a fifth ethyl ester phase, respectively; the fifth aqueous phase is reused in step (2) to dissolve the crude sucralose concentrate.

Preferably, in step (1), the residual amount of ethyl acetate in the syrup is less than 0.1 wt%.

Preferably, in step (1), the content of sucralose-6-acetate in the first aqueous phase is less than 0.5 g/L.

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

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 h.

Preferably, in step (2), the content of methanol in the crude sucralose concentrate is less than 0.1 wt %.

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

The ethyl ester phases obtained from the first and second ethyl ester extractions are combined as the second ethyl ester phase;

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

Preferably, in step (4), the number of water washings is 4 to 6 times; the volume ratio of the second ethyl ester phase to the water used for the single water washing is 1:0.1 to 0.15;

The aqueous phases obtained from the first and second water washings are combined as the fourth aqueous phase;

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

Preferably, in step (4), the content of sucralose in the third aqueous phase is less than 0.5 g/L.

Preferably, in step (5), the water content of the third ethyl ester phase concentrate is less than 0.5 wt%.

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

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

Preferably, in step (6), the number of water washings is 3 to 4 times; the volume ratio of the fourth ethyl ester phase to the single water used for the water washing is 1:0.3 to 0.5;

The aqueous phases obtained from the first and second water washings are combined as the fifth aqueous phase;

The aqueous phase obtained from the third to fourth water washings is used for washing the fourth ethyl ester phase in the preparation process of the next batch of crude sucralose.

Preferably, in step (6), the sucralose content in the fifth ethyl ester phase is less than 0.1 g/L.

The present invention provides a method for preparing crude sucralose using an improved alcohol-water alkaline hydrolysis system. The present invention uses an alkali metal hydroxide as an alkaline hydrolysis reagent, and the alkaline hydrolysis is performed in a methanol-water system. Sucralose-6-acetate, sucralose diester and sucralose-6-acetate are all alkaline hydrolyzed to generate corresponding sucralose and sucralose, and sucralose continues to be dechlorinated to form sucralose, so that the sucralose-6-acetate and impurities (sucralose diester and sucralose-6-acetate) in the first aqueous solution are converted into sucralose, thereby significantly improving the raw material conversion rate and the yield of sucralose. Compared with the method for preparing sucralose by alkaline hydrolysis using high-purity sucralose-6-acetate as a raw material, the raw material conversion rate and the yield of sucralose in the method provided by the present invention are significantly improved. The present invention performs alkaline hydrolysis in a methanol-water system, which can improve the efficiency of alkaline hydrolysis, reduce the precipitation of fat-soluble impurities during the cooling alkaline hydrolysis process, and cause uneven stirring and reduced mass transfer effect, thereby providing product yield. The method provided by the present invention uses multiple concentrations and multiple extractions and back extractions between ethyl acetate/water dual solvent systems for separation, so that fat-soluble impurities and water-soluble impurities reach a balance in the system, and can also avoid the phenomenon of sugar caramelization during the concentration process, thereby allowing sucralose to fully crystallize in ethyl acetate and improve the yield of sucralose. Inorganic salts (such as sodium chloride, potassium chloride, and ammonium chloride) are easily soluble in water and insoluble in ethyl acetate. After alkaline hydrolysis and adjusting the pH value to neutral, there are more inorganic salts in the sucralose alkaline hydrolyzate obtained. If ethyl acetate is used, sucralose can be extracted from the system under heating or room temperature, but the amount of ethyl acetate used is large, and the high-salt wastewater remaining after extraction also needs to be evaporated and crystallized to collect inorganic salts. The method provided by the present invention utilizes the property that inorganic salts (such as sodium chloride, potassium chloride, and ammonium chloride) are insoluble in ethyl acetate, and directly concentrates the sucralose alkaline hydrolyzate 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 the inorganic salts from sucralose. Moreover, the present invention reuses the fourth aqueous phase in step (2) to dissolve the crude sucralose concentrate, and does not need to be applied before alkaline hydrolysis, thereby reducing the volume of the alkaline hydrolysis solution, reducing the alkaline hydrolysis pressure, and reducing the amount of high COD wastewater, thereby reducing the subsequent treatment costs of high-salt wastewater and high COD wastewater, alleviating subsequent environmental protection pressure, and having high industrial application value.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a process flow chart of preparing crude sucralose using an improved alcohol-water alkaline hydrolysis system in Example 1.

Detailed ways

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

The present invention provides a method for preparing crude sucralose by using an improved alcohol-water alkaline hydrolysis system, comprising the following steps:

(1) extracting a crude aqueous solution of sucralose-6-acetate with ethyl acetate to obtain a first ethyl ester phase and a first aqueous phase; concentrating the first ethyl ester phase to obtain a syrup; dissolving the syrup in a methanol-water mixed solvent to obtain a sucralose-6-acetate methanol aqueous solution; the crude aqueous solution of sucralose-6-acetate includes sucralose-6-acetate, sucralose diester and tetrachlorosucrose-6-acetate;

(2) mixing the sucralose-6-acetate methanol aqueous solution with an alkali metal hydroxide to perform an alkaline hydrolysis reaction, neutralizing the obtained reaction solution to obtain a sucralose alkaline hydrolyzate; concentrating the sucralose alkaline hydrolyzate to obtain a crude sucralose concentrate, and dissolving the crude sucralose concentrate in water to obtain a second aqueous phase;

(3) extracting the second aqueous phase with ethyl acetate to obtain a second ethyl ester phase and a third aqueous phase;

(4) washing the second ethyl ester phase with water to obtain a fourth aqueous phase and a third ethyl ester phase, respectively; the fourth aqueous phase is reused in step (2) to dissolve the crude sucralose concentrate;

(5) concentrating the third ethyl ester phase to obtain a third ethyl ester phase concentrate; dissolving the third ethyl ester phase concentrate in ethyl acetate to obtain a crude sucralose ethyl acetate solution; crystallizing the crude sucralose ethyl acetate solution to obtain crude sucralose and a fourth ethyl ester phase, respectively;

(6) washing the fourth ethyl ester phase with water to obtain a fifth aqueous phase and a fifth ethyl ester phase, respectively; the fifth aqueous phase is reused in step (2) to dissolve the crude sucralose concentrate.

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

The invention conducts ethyl acetate extraction on a crude aqueous solution of sucralose-6-acetate to obtain a first ethyl ester phase and a first aqueous phase respectively; the first ethyl ester phase is concentrated to obtain syrup; the syrup is dissolved in a methanol-water mixed solvent to obtain a sucralose-6-acetate methanol aqueous solution; the crude aqueous solution of sucralose-6-acetate comprises sucralose-6-acetate, sucralose diester and tetrachlorosucrose-6-acetate.

In the present invention, in the raw material solution, the content of sucralose-6-acetate is preferably 50-80 g/L, more preferably 50-70 g/L; the mass ratio of sucralose-6-acetate, sucralose diester and tetrachlorosucrose-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 NH ₄ Cl and organic impurities, and the concentration of the NH ₄ Cl is preferably 80-150 g/L, more preferably 85-120 g/L; the concentration of the organic impurities is preferably 30-80 g/L, more preferably 30-50 g/L.

The present invention has no particular limitation on the preparation method of the crude sucralose-6-acetate aqueous solution (referred to as the first aqueous solution). The crude sucralose-6-acetate aqueous solution of the above components can be obtained by using a preparation method for preparing crude sucrose-6-acetate using sucrose as an initial raw material, which is well known to those skilled in the art. Specifically, sucrose is used as a raw material, N,N-dimethylformamide (DMF) is a solvent, organic tin is a catalyst, and acetic anhydride is used as an acylating agent to prepare a solution containing sucrose-6-acetate; then the obtained solution containing sucrose-6-acetate is sequentially chlorinated (sulfoxide chloride), neutralized with ammonia water, vacuum concentrated to dryness, and dissolved in water to obtain a crude sucralose-6-acetate aqueous solution.

In the present invention, the temperature of the ethyl acetate extraction is preferably 40-60°C, more preferably 45-55°C, and further preferably 50°C; the present invention has no special limitation on the number of ethyl acetate extractions, and the content of sucralose-6-acetate in the aqueous phase (i.e., the first aqueous phase) obtained by the last ethyl acetate extraction is less than 0.5g/L, specifically 4-8 times; the time of a single ethyl acetate extraction is preferably 10-30min, more preferably 15-25min; the volume ratio of the crude sucralose-6-acetate aqueous solution to the ethyl acetate used for the single ethyl acetate extraction is preferably 1:0.2-0.6, more preferably 1:0.4-0.5. In the present invention, the first aqueous phase is preferably subjected to high-salt wastewater treatment.

The present invention has no special limitation on the concentration method, and a concentration method well 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 has no special limitation on the concentration time, and the concentration can be performed until the residual amount of ethyl acetate in the syrup is less than 0.1wt%. The present invention can avoid the generation of byproducts such as acetic acid and ethanol from ethyl acetate in the subsequent alkaline hydrolysis step by controlling the residual amount of ethyl acetate in the syrup, thereby further improving the purity and yield of sucralose.

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

After obtaining the sucralose-6-acetate methanol aqueous solution, the present invention mixes the sucralose-6-acetate methanol aqueous solution with an alkali metal hydroxide to perform an alkaline hydrolysis reaction, neutralizes the obtained reaction solution to obtain a sucralose alkaline hydrolyzate; concentrates the sucralose alkaline hydrolyzate to obtain a crude sucralose concentrate, and dissolves the crude sucralose concentrate in water to obtain a second aqueous phase.

In the present 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 alkali metal hydroxide aqueous solution, and the concentration of the alkali metal hydroxide aqueous solution is preferably 10-40wt%, more preferably 20-35wt%; the present invention has no special limitation on the amount of the alkali metal hydroxide, as long as the pH value of the alkaline hydrolysis reaction is 11.5-12.5, and the pH value is more preferably 11.8-12.5, and further preferably 12-12.3; the temperature of the alkaline hydrolysis reaction is preferably 0-20°C, more preferably 5-15°C, and further preferably 5-10°C; the time of the alkaline hydrolysis reaction is preferably 0.5-2h, more preferably 1-1.5h. The present invention performs alkaline hydrolysis under the above conditions, sucralose diester can be hydrolyzed to generate sucralose, sucralose-6-acetate can be dechlorinated and hydrolyzed to generate sucralose, and the generation of byproducts due to the excessively high pH value of the alkaline hydrolysis reaction or the excessively high temperature of the alkaline hydrolysis reaction can be avoided; the alkaline hydrolysis is performed in a methanol-water system, which can increase the solubility of fat-soluble impurities in an aqueous system under low temperature conditions, thereby improving the efficiency of alkaline hydrolysis. Moreover, the present invention uses an alkali metal hydroxide as an alkaline hydrolysis reagent and performs alkaline hydrolysis in a methanol-water system. Compared with the traditional sodium methoxide/methanol reaction system with higher hazards, it is not necessary to use high-purity alkaline sucralose-6-acetate, and the purification step of sucralose-6-acetate is omitted, which greatly shortens the process and reduces the production cost.

In the present invention, the acid used for neutralization preferably includes hydrochloric acid; the concentration of the acid is preferably 15-35wt%, more preferably 20-30wt%. The present invention has no particular limitation on the amount of the acid, as long as the system can be neutralized to a pH value of 6.8-7.

The present invention has no particular limitation on the concentration method, and a concentration method well known to those skilled in the art may 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 has no particular limitation on the concentration time, and the concentration may be performed until the content of methanol in the crude sucralose concentrate is less than 0.1 wt %.

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

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

In the present invention, the number of ethyl acetate extractions is preferably 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; in the present invention, the ethyl ester phases obtained by the first to second ethyl acetate extractions are preferably combined as the second ethyl ester phase; the ethyl ester phases obtained by the third to seventh ethyl acetate extractions are preferably used for the ethyl acetate extraction of the second aqueous phase in the next batch of crude sucralose preparation process. Specifically, the ethyl ester phase obtained by 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 process, and the fourth ethyl acetate extraction is used for the first ethyl acetate extraction of the second aqueous phase in the next batch of crude sucralose preparation process. The obtained ethyl ester phase is used for the second ethyl acetate extraction of the second aqueous phase in the next batch of crude sucralose preparation process, the ethyl ester phase obtained by the fifth ethyl acetate extraction is used for the third ethyl acetate extraction of the second aqueous phase in the next batch of crude sucrose preparation process, the ethyl ester phase obtained by the sixth ethyl acetate extraction is used for the fourth ethyl acetate extraction of the second aqueous phase in the next batch of crude sucrose preparation process, and the ethyl ester phase obtained by the seventh ethyl acetate extraction is used for the fifth ethyl acetate extraction of the second aqueous phase in the next batch of crude sucralose preparation process (i.e., the ethyl ester phases obtained by the third to seventh ethyl acetate extractions are sequentially used for the first to fifth ethyl acetate extractions of the second aqueous phase in the next batch of crude sucralose preparation process), and the sixth to seventh ethyl acetate extractions of the second aqueous phase in the next batch of crude sucralose preparation process are preferably carried out using pure ethyl acetate.

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

In the present invention, the number of water washings is preferably 4 to 6 times; the volume ratio of the second ethyl ester phase to the single water used for water washing is preferably 1:0.1 to 0.15, more preferably 1:0.11 to 0.14, and further preferably 1:0.12 to 0.13; in the present invention, the aqueous phases obtained from the first to second water washings are preferably combined as the fourth aqueous phase; the aqueous phases obtained from the third to sixth water washings are preferably 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 fourth water washing. The aqueous phase obtained from the fifth water washing is used for the third water washing of the second ethyl ester phase in the next batch of crude sucralose preparation process, the aqueous phase obtained from the sixth water washing is used for the fourth water washing of the second ethyl ester phase in the next batch of crude sucrose preparation process, and the aqueous phase obtained from the seventh water washing is used for the fifth 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 to seventh water washings are used sequentially for the first to fifth water washings of the second ethyl ester phase in the next batch of crude sucralose preparation process). The sixth to seventh water washings of the second ethyl ester phase in the next batch of crude sucralose preparation process are preferably carried out with pure water.

In the present invention, the content of sucralose in the third aqueous phase is preferably less than 0.5 g/L.

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 a crude sucralose ethyl acetate liquid; and crystallizes the crude sucralose ethyl acetate liquid to obtain crude sucralose and a fourth ethyl ester phase, respectively.

The present invention has no particular limitation on the concentration method, and a concentration method well known to those skilled in the art may 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 has no particular limitation on the concentration time, and the concentration may be performed until the water content of the third ethyl ester phase concentrate is less than 0.5 wt %.

The present invention has no particular limitation on the amount of ethyl acetate used, and the sugar content (Bx) of the crude sucralose ethyl acetate solution is 50-70 wt %, and the sugar content is more preferably 55-65 wt %, and further preferably 60 wt %.

In the present invention, the crystallization temperature is preferably 30-50°C, more preferably 35-45°C, and further preferably 40°C; the crystallization time is preferably 6-12h, more preferably 7-11h, and further preferably 8-10h.

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

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

Water-soluble impurities and fat-soluble impurities are both produced by sucrose in a series of reaction processes, and therefore have a similar main structure to sucralose, so that water-soluble impurities, fat-soluble impurities and sucralose all have a certain degree of mutual solubility. The present invention utilizes the relationship between the three, and selects water and ethyl acetate as solvents for removing water-soluble impurities and fat-soluble impurities, so that both solvents can dissolve and carry sucralose, realize the exchange of sucralose in the two solvents, and enrich sucralose in ethyl acetate, and obtain crude sucralose by crystallization therefrom.

The technical solutions in the present invention will be described clearly and completely below in conjunction with the embodiments of the present invention. Obviously, the described embodiments are only a part of the embodiments of the present invention, not all of them. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without creative work are within the scope of protection of the present invention.

The content of each substance in the following embodiments was measured by high performance liquid chromatography (HPLC) under the following conditions using an external standard method. The analytical conditions of the HPLC were: Shimadzu high performance liquid chromatograph, equipped with RID-10A differential refractometer, LC-10ADVP high pressure pump, CTO-10ASVP constant temperature box; chromatographic column: Agilent XDB C18 column (250mm×4.6mm, 5μm); mobile phase: methanol-0.125wt% potassium hydrogen phosphate aqueous solution (4:6, v/v); column temperature: 40°C; mobile phase flow rate: 1.0mL/min; wherein methanol (chromatographic grade), potassium hydrogen phosphate (analytical grade), and water are ultrapure water.

The preparation method of the crude aqueous solution of sucralose-6-acetate (referred to as the first aqueous solution, the components are shown in Table 1) used in the following examples is as follows: using sucrose as a raw material, DMF as a solvent, organotin as a catalyst, and acetic anhydride as an acylating agent to prepare a solution containing sucrose-6-acetate; the sucrose-6-acetate solution is sequentially chlorinated, neutralized with ammonia water, concentrated to dryness in vacuo, and dissolved in water to obtain a crude aqueous solution of sucralose-6-acetate.

Table 1 Composition of the first aqueous solution

Components	content
Sucralose-6-acetate	55.2g/L
Sucralose diester	5.4g/L
Sucralose-6-acetate	4.0g/L
NH 4 Cl	88.9g/L
Other organic impurities	33.2g/L
water	84.1wt％

Example 1

The crude sucralose is prepared using the process flow chart shown in FIG1 , and the specific steps are as follows:

(1) 1000 mL of the first aqueous solution was heated, and extracted with ethyl acetate (500 mL per time) at 45° C. for 4 times. After the extraction, the ester phases were combined as the first ethyl ester phase, and the aqueous phases were combined as the first aqueous phase; the content of sucralose-6-acetate in the first aqueous phase was 0.08 g/L, and the first aqueous phase was subjected to high-salt wastewater treatment; the first ethyl ester phase was vacuum concentrated to dryness (abbreviated as concentrated to dryness), and 50 wt % methanol aqueous solution was added to the obtained syrup (ethyl acetate content <0.5 g/L) to dissolve it, and the 50 wt % methanol aqueous solution was fixed to 800 mL to obtain sucralose-6-acetate methanol aqueous solution.

(2) cooling the sucralose-6-acetate methanol aqueous solution to 7°C, then dropping a 32 wt% sodium hydroxide aqueous solution, and performing alkaline hydrolysis reaction at 7°C and pH 12.5 for 1 hour. At the end of the reaction, the sucralose-6-ethyl ester content was 0.4 g/L. Then dropping a 30 wt% dilute hydrochloric acid solution to neutralize to pH = 7, concentrating the obtained sucralose alkaline hydrolyzate, and adding water (volume ratio of sucralose-6-acetate methanol aqueous solution to water = 1:0.7) to the obtained sucralose crude concentrate (methanol content 0.09 wt%) to dissolve it to obtain a second aqueous phase.

(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 a single extraction = 1:2), and the ester phases obtained from the first and second extractions are combined to form a second ethyl ester phase; all aqueous phases are combined as a third aqueous phase, and the third aqueous phase is subjected to high-salt wastewater treatment; the ethyl ester phases obtained from the third to fifth ethyl acetate extractions are sequentially used for the first to third ethyl acetate extractions of the second aqueous phase in the preparation process of the next batch of crude sucralose. At this time, the fourth to fifth ethyl acetate extractions of the second aqueous phase in the preparation process of the next batch of crude sucralose are carried out using pure ethyl acetate.

(4) washing the second ethyl ester phase with water for 4 times (the volume ratio of the second ethyl ester phase to the water used for a single wash = 1:0.1) and layering to obtain a third ethyl ester phase and a fourth aqueous phase; wherein the aqueous phase obtained from the first and second washes is used as the fourth aqueous phase to dissolve the crude sucralose concentrate in step (2) of preparing the next batch of crude sucralose; and the aqueous phase obtained from the third and fourth washes is used in turn for the first and second washes of the second ethyl ester phase in the process of preparing the next batch of crude sucralose.

(5) the third ethyl ester phase was concentrated and dried to remove water and part of the ethyl acetate, ethyl acetate was added to the obtained third ethyl ester phase concentrate (water content of 0.3 wt%) to adjust the sugar content Bx to 55 wt%, and then crystallized at 45 ° C for 8 h, and filtered to obtain crude sucralose and a fourth ethyl ester phase respectively;

(6) Adding pure water to the fourth ethyl ester phase (the volume ratio of the fourth ethyl ester phase to pure water = 1:0.5) to wash the residual sugar until the sucralose content is 0.08 g/L, and obtaining a fifth aqueous phase and a fifth ethyl ester phase, respectively. The fifth aqueous phase is used to dissolve the sucralose crude concentrate in step (2) of preparing the next batch of sucralose crude products; 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;

(7) According to the operations of steps (1) to (5) (recorded as recycling 0 times), the fourth aqueous phase, the fifth aqueous phase, the sixth aqueous phase, the sixth ester phase and the seventh ethyl ester phase were recycled 17 times, wherein the step (3) of "adding water (volume ratio of sucralose-6-acetate methanol aqueous solution to water = 1:0.7) to dissolve the obtained crude sucralose concentrate (water content of 0.1 wt%)" was replaced by "adding the fourth aqueous phase and the fifth aqueous phase to the obtained crude sucralose concentrate "dissolve"; the first to third ethyl acetate extractions of the second aqueous phase in step (3) are sequentially carried out using the ethyl ester phase obtained by the third to fifth ethyl acetate extractions of the second aqueous phase in step (3) in the process of preparing the previous batch of crude sucralose, and the fourth to fifth ethyl acetate extractions of the second aqueous phase are carried out using pure ethyl acetate; the first to second water washings of the second ethyl ester phase in step (4) are sequentially carried out using the aqueous phase obtained by the third to fourth water washings of the second ethyl ester phase in step (4) in the process of preparing the previous batch of crude sucralose, and the third to fourth water washings of the second ethyl ester phase are washed with pure water. The quality, purity and yield of the crude sucralose obtained by repeating the cycle 17 times are shown in Table 2.

Table 2 Purity and yield of crude sucralose

Note: The yield is the mass of the final sucralose obtained divided by the mass of sucralose-6-acetate completely converted into sucralose. Both sucralose diester and sucralose-6-acetate can be converted into sucralose after alkaline hydrolysis, and the actual yield will exceed 100%. The theoretical maximum yield in Example 1 is 117.17%.

During the application process, the following conditions are met: the content of sucralose-6-acetic acid in the first aqueous phase is less than 0.5g/L, the content of sucralose in the third aqueous phase is less than 0.5g/L, and the content of sucralose in the fifth ethyl ester phase is less than 0.1g/L. If not achieved, an additional extraction with ethyl acetate or pure water washing is required to avoid loss of the target substance. The water content in the system of the third ethyl ester phase is less than 0.5wt% during the concentration process, and only fresh ethyl acetate can be used to carry water. The use of other water-carrying agents will affect the subsequent separation of solvents. When the water content of the concentrate of the third ethyl ester phase exceeds 0.5wt%, it will seriously affect the crystallization of sucralose in the ethyl acetate phase.

During the application process, sucralose and impurities are in a state of equilibrium in the ethyl ester phase, that is, the application is cyclically applied until the sucralose yield is above 105%. The characteristics of the system adopted by the present invention are: thanks to the conversion of sucralose diester and sucralose-6-acetate, sucralose can achieve a yield of more than 110% (calculated by the conversion of sucralose-6-acetate into sucralose); the mutual washing and application of the ester phase and the aqueous phase can avoid the loss caused by the residue of sucralose in the sugar residue and wastewater to the greatest extent. Moreover, the fourth aqueous phase and the fifth aqueous phase contain residual sucralose, which improves the yield of sucralose.

From the above examples, it can be found that in the initial several operation processes, such as the 1st to 3rd cycle application process, the yield is low because the ethyl acetate and water circulating in the system contain low components that can be converted into sucralose. After four cycles, if the yield is calculated based on the conversion of all sucralose-6-acetate into sucralose, the yield will exceed 100%. The reason is that the crude aqueous solution of sucralose-6-acetate also includes other components (sucralose diester and sucralose-6-acetate) that can be converted into sucralose. The method provided by the present invention can convert sucralose diester and sucralose-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 a raw material, the method provided by the present invention has a significantly improved yield of sucralose. In addition, the present invention uses the crude aqueous solution of sucralose-6-acetate as a raw material and does not need to be purified, so the process is simpler, avoiding the loss of sucralose-6-acetate caused by the need to purify sucralose-6-acetate before alkaline hydrolysis in the traditional process.

Moreover, the present invention separates inorganic salts from the system before performing ethyl acetate/water double solvent extraction-strip extraction, thereby reducing the difficulty of subsequent high-salt wastewater treatment. The solubility of sucralose in ethyl acetate is relatively low, and the present invention introduces fat-soluble caramel impurities in the system into ethyl acetate during the fourth ethyl ester phase and the fourth aqueous phase are recycled, which can significantly increase the solubility of sucralose in ethyl acetate, and adopts extraction, water washing, and recycling methods to balance the impurities in the system, so that sucralose can be enriched and crystallized in ethyl acetate; by increasing the number of ethyl acetate/water double solvent extraction-strip extraction, it is avoided that the subsequent mother liquor containing sucralose/or washing water needs to return to the concentration step to achieve the purpose of recovery through concentration. In addition, in the crystallization mother liquor, since it is an ethyl acetate solvent system, there are more fat-soluble impurities, and the solubility of sucralose in water is relatively high, so the uncrystallized sucralose can be recycled and applied by multiple water washings, and fat-soluble impurities are excluded. By the implementation of the above means, 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.

In summary, the method provided by the present invention uses an alkali metal hydroxide and methanol water system for alkaline hydrolysis, and an ethyl acetate/water dual system for extraction and impurity removal, so that sucralose-6-acetate, sucralose diester and tetrachlorosucrose-6-acetate can be converted into sucralose, and sucralose can be fully enriched and crystallized in the ethyl ester phase, thereby avoiding the loss caused by the need for purification before alkaline hydrolysis of sucralose-6-acetate in the traditional process, as well as the loss of some useful impurities, and significantly improving the yield of sucralose. Inorganic salts are discharged in the form of high brine instead of solid form, and the same efficiency of obtaining crude sucralose can also be achieved. Moreover, the aqueous phase containing sucralose (the fourth aqueous phase and the fifth aqueous phase) produced in the latter stage is used as a solvent to dissolve the crude sucralose concentrate, so that the aqueous phase can be used, creating greater value, and having great industrial prospects.

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 (14)

1. A method for preparing crude sucralose using an improved alcohol-water alkaline hydrolysis system, characterized in that it comprises the following steps:

   (1) extracting a crude aqueous solution of sucralose-6-acetate with ethyl acetate to obtain a first ethyl ester phase and a first aqueous phase; concentrating the first ethyl ester phase to obtain a syrup; dissolving the syrup in a methanol-water mixed solvent to obtain a sucralose-6-acetate methanol aqueous solution; the crude aqueous solution of sucralose-6-acetate includes sucralose-6-acetate, sucralose diester and tetrachlorosucrose-6-acetate;

   (2) mixing the sucralose-6-acetate methanol aqueous solution with an alkali metal hydroxide to perform an alkaline hydrolysis reaction, neutralizing the obtained reaction solution to obtain a sucralose alkaline hydrolyzate; concentrating the sucralose alkaline hydrolyzate to obtain a crude sucralose concentrate, and dissolving the crude sucralose concentrate in water to obtain a second aqueous phase;

   (3) extracting the second aqueous phase with ethyl acetate to obtain a second ethyl ester phase and a third aqueous phase;

   (4) washing the second ethyl ester phase with water to obtain a fourth aqueous phase and a third ethyl ester phase, respectively; the fourth aqueous phase is reused in step (2) to dissolve the crude sucralose concentrate;

   (5) concentrating the third ethyl ester phase to obtain a third ethyl ester phase concentrate; dissolving the third ethyl ester phase concentrate in ethyl acetate to obtain a crude sucralose ethyl acetate solution; crystallizing the crude sucralose ethyl acetate solution to obtain crude sucralose and a fourth ethyl ester phase, respectively;

   (6) washing the fourth ethyl ester phase with water to obtain a fifth aqueous phase and a fifth ethyl ester phase, respectively; the fifth aqueous phase is reused in step (2) to dissolve the crude sucralose concentrate.
2. The method according to claim 1, characterized in that in step (1), the residual amount of ethyl acetate in the syrup is less than 0.1wt%.
3. The method according to claim 1, characterized in that in step (1), the content of sucralose-6-acetate in the first aqueous phase is less than 0.5 g/L.
4. The method according to claim 1, characterized in that in step (1), the concentration of methanol in the methanol-water mixed solvent is 10 to 60 wt%.
5. The method according to claim 1, characterized in that 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 2h.
6. The method according to claim 1, characterized in that in step (2), the content of methanol in the crude sucralose concentrate is less than 0.1 wt%.
7. The method according to claim 1, characterized in that, in step (3), the number of ethyl acetate extractions is 5 to 7 times; the volume ratio of the second aqueous phase to the ethyl acetate used in a single ethyl acetate extraction is 1:1 to 2;

   The ethyl ester phases obtained from the first and second ethyl ester extractions are combined as the second ethyl ester phase;

   The ethyl ester phase obtained from the 3rd to 7th ethyl acetate extractions is used for the ethyl acetate extraction of the second aqueous phase in the preparation process of the next batch of crude sucralose.
8. The method according to claim 1, characterized in that, in step (4), the number of water washings is 4 to 6 times; the volume ratio of the second ethyl ester phase to the single water used for the water washing is 1:0.1 to 0.15;

   The aqueous phases obtained from the first and second water washings are combined as the fourth aqueous phase;

   The aqueous phase obtained from the 3rd to 6th water washing is used for washing the second ethyl ester phase in the preparation process of the next batch of crude sucralose.
9. The method according to claim 1 or 8, characterized in that in step (4), the content of sucralose in the third aqueous phase is less than 0.5 g/L.
10. The method according to claim 1, characterized in that in step (5), the water content of the third ethyl ester phase concentrate is less than 0.5wt%.
11. The method according to claim 1 or 10, characterized in that in step (5), the sugar content of the crude sucralose ethyl acetate solution is 50 to 70 wt%.
12. The method according to claim 1, characterized in that in step (5), the crystallization temperature is 30 to 50°C and the time is 6 to 12 hours.
13. The method according to claim 1, characterized in that, in step (6), the number of water washings is 3 to 4 times; the volume ratio of the fourth ethyl ester phase to the single water used for the water washing is 1:0.3 to 0.5;

    The aqueous phases obtained from the first and second water washings are combined as the fifth aqueous phase;

    The aqueous phase obtained from the third to fourth water washings is used for washing the fourth ethyl ester phase in the preparation process of the next batch of crude sucralose.
14. The method according to claim 1, characterized in that the sucralose content in the fifth ethyl ester phase is less than 0.1 g/L.

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