WO2022141229A1 - Sucralose preparation method, crude product solution, and sucralose - Google Patents

Abstract

A sucralose preparation method, a crude product solution, and sucralose, the method comprising: dissolving sucralose-6-ethyl ester in ethanol to form a sucralose-6-ethyl ester reaction solution; distilling the sucralose-6-ethyl ester reaction solution to remove the moisture therein; adding an alkaline catalyst such as sodium hydroxide or potassium hydroxide to the sucralose-6-ethyl ester reaction solution to form a sucralose mixed solution; and filtering the sucralose mixed solution to obtain a sucralose crude product solution.

Description

Preparation method of sucralose, crude product solution and sucralose technical field

The invention belongs to the technical field of fine chemicals, and particularly relates to a preparation method of sucralose, a crude product solution and sucralose.

Background of the Invention

Sucralose belongs to a new generation of sweeteners, which has the advantages of high sweetness, no calories, good stability and high safety, and has a very broad market prospect. Regarding the synthesis process of sucralose, great progress has been made since the advent of sucralose. So far, the mainstream synthesis process is the single-group protection method: the 6-position hydroxyl group with the highest activity of sucrose is selectively protected, usually in the form of acetate, that is, to generate sucrose-6-ethyl ester, sucrose-6-ethyl ester The three hydroxyl groups at the 4, 1' and 6' positions of sucralose are selectively chlorinated to generate sucralose-6-ethyl ester, and the sucralose-6-ethyl ester is deacetylated to generate sucralose.

For the deacetylation step, the existing technology basically adopts a catalytic amount of sodium methoxide (MeONa) as a catalyst, and alcoholysis is carried out in methanol (MeOH) to remove the acetyl group to generate sucralose, and by-product methyl acetate etc. . The use of MeONa/MeOH catalytic system has the advantages of mild conditions, rapid reaction and high yield, but it also has certain disadvantages. For example, MeONa is relatively expensive and cannot be recycled, which increases the production cost; the generated methyl acetate can not be used as a by-product. In the technological process, the types of materials that need to be operated in the technological process are added.

In addition, because the sucralose-6-ethyl ester as the reaction raw material often contains a small amount of water, there is a hydrolysis reaction as a side reaction, which competes with the main reaction of alcoholysis, which not only causes a large amount of waste of catalyst MeONa, but also generates sodium acetate. The cationic resin is exchanged to generate acetic acid, and the acetic acid remains in the sucralose product, which makes the product have an obvious acidic odor, which seriously affects the product quality.

Therefore, there is still a lot of room for improvement and improvement in the process of deacetylating sucralose-6-ethyl ester to synthesize sucralose. It should be noted that the statements herein merely provide background information related to the present application and do not necessarily constitute prior art.

SUMMARY OF THE INVENTION

In view of the above problems, the present application is proposed in order to provide a preparation method of sucralose, its crude product solution and sucralose which overcome the above problems or at least partially solve the above problems.

According to one aspect of the present application, a preparation method of sucralose is provided, comprising:

Dissolving step: dissolving sucralose-6-ethyl ester in ethanol to form a sucralose-6-ethyl ester reaction solution;

Distillation step: distilling the sucralose-6-ethyl ester reaction solution to remove moisture therein;

Catalysis step: adding an alkaline catalyst to the sucralose-6-ethyl ester reaction solution obtained in the distillation step, and reacting under preset conditions, so that the sucralose-6-ethyl ester undergoes a deacylation reaction , forming a mixed solution of sucralose; and

The step of removing impurities: filtering the mixed solution of sucralose to obtain a crude product solution of sucralose.

According to another aspect of the present application, a crude sucralose product solution is provided, which is prepared by the above-mentioned preparation method, wherein the by-product acetic acid content is less than or equal to 230 ppm.

According to yet another aspect of the present application, a sucralose is provided, which is obtained by crystallizing and refining the above-mentioned sucralose crude product solution.

To sum up, the beneficial effects of the present application are as follows: the present application adopts ethanol as a solvent, and the by-product ethyl acetate is a species originally used in the sucralose production process flow, and can be applied to the process, thereby reducing the number of The types of materials to be treated in the sucralose generation process significantly reduce the difficulty and cost of post-treatment; and the water in the reaction system can be removed by azeotropic distillation to avoid the occurrence of hydrolysis side reactions, which greatly reduces the The content of the by-product acetic acid improves the product quality of sucralose; and the catalyst in the present application can be recycled through simple treatment, thereby reducing the production cost of sucralose.

The above description is only an overview of the technical solution of the present application. In order to be able to understand the technical means of the present application more clearly, it can be implemented according to the content of the description, and in order to make the above-mentioned and other purposes, features and advantages of the present application more obvious and easy to understand , and the specific embodiments of the present application are listed below.

Brief Description of Drawings

Various other advantages and benefits will become apparent to those of ordinary skill in the art upon reading the following detailed description of the preferred embodiments. The drawings are for purposes of illustrating preferred embodiments only and are not to be considered limiting of the application. Also, the same components are denoted by the same reference numerals throughout the drawings. In the attached image:

FIG. 1 shows a schematic flowchart of a method for preparing sucralose according to an embodiment of the present application.

MODES OF IMPLEMENTING THE INVENTION

Exemplary embodiments of the present application will be described in more detail below with reference to the accompanying drawings. While exemplary embodiments of the present application are shown in the drawings, it should be understood that the present application may be embodied in various forms and should not be limited by the embodiments set forth herein. Rather, these embodiments are provided so that the application will be more thoroughly understood, and will fully convey the scope of the application to those skilled in the art.

Although MeONa/MeOH (MeONa/MeOH represents the coexistence of the two, specifically using MeONa as a catalyst and MeOH as a solvent) system is a classic combination, it is widely used in the deacetylation of sugars (ie Zemplén reaction), but the MeONa/MeOH system is widely used. As a catalyst, there are many drawbacks, such as large catalyst consumption and difficult recovery; and the by-product methyl acetate increases the material types of the overall reaction system, and increases the difficulty and workload of post-processing.

The idea of the present application is that, in view of the above problems, the inventors found that in the Zemplén reaction system, MeONa can be replaced by many different types of bases, which can be strong bases, weak bases, organic bases or inorganic bases, etc., and also include bases The deacetylation process can be smoothly catalyzed by bases in immobilized form such as anion resins. On this basis, the present application uses ethanol (EtOH) as a solvent, and cheaper and readily available bases as catalysts, such as sodium hydroxide (NaOH), potassium hydroxide (KOH), etc., to successfully realize sucralose-6- At the same time, the catalytic deacetylation process of ethyl ester makes up for many deficiencies of the MeONa/MeOH catalytic system.

In addition, the inventor also found that, because the sucralose-6-ethyl ester as the reaction raw material often contains a small amount of water, in the presence of MeONa, the hydrolysis of the sucralose-6-ethyl ester will be caused, and the hydrolysis reaction is used as a side reaction. , competes with the main reaction of alcoholysis, will consume a large amount of catalyst MeONa, and generate sodium acetate (AcONa), and sodium acetate is exchanged with acidic cation resin to generate acetic acid (HOAc). In the sucralose product, the product has an obvious acidic odor, which seriously affects the product quality. In view of the above problems, the present application adopts the means of distillation to remove the water in the reaction system by azeotroping of ethanol and water, so as to avoid the side reaction of hydrolysis to generate acetic acid.

Fig. 1 shows the schematic flow sheet of the preparation method of sucralose according to an embodiment of the present application, including:

Dissolving step S110: Dissolving sucralose-6-ethyl ester in ethanol to form a sucralose-6-ethyl ester reaction solution.

At present, the most widely used method for preparing sucralose is the single-group protection method. Taking sucralose-6-acetate as an example, the chemical reaction process is shown in the reaction formula (1).

Reaction (1)

From the reaction formula (1), it can be seen that the 6-position hydroxyl group has the highest activity of sucrose. In the single-group protection method, it is protected in the form of acetate. Specifically, sucrose and acetic anhydride are used for protection. The esterification reaction produces sucrose-6-ethyl ester. After the selective chlorination of the three hydroxyl groups at the 4, 1' and 6' positions, the deacylation reaction is carried out to finally generate sucralose. protection to avoid substitution of the hydroxyl group at the 6-position by a chlorine atom.

The present application mainly improves the step of deacetylation. In the prior art, sodium methoxide (MeONa) is usually used as a catalyst and methanol (MeOH) is used as a solvent for the deacetylation reaction. Because there is usually a small amount of water in the sucrose-6-acetate solution, in the process of deacylation, a side reaction of hydrolysis will occur, which will compete with the main reaction of alcoholysis, such as the reaction process such as the reaction formula ( 2) shown.

Reaction (2)

From the prior art shown in reaction formula (2), in the MeONa/MeOH catalytic system process, there is competition between the main reaction of alcoholysis and the side reaction of hydrolysis, and the hydrolysis reaction will consume the catalyst MeONa, and generate sodium acetate, and the sodium acetate is processed by The acid cation resin exchanges to produce acetic acid, which remains in the final product and affects the odor and taste of sucralose. Moreover, methyl acetate is generated by using methanol as a solvent, which increases the types of materials in the reaction system and increases the burden for post-processing.

In view of the above problems, the application adopts ethanol as solvent, it should be noted that the ethanol adopted in the application is dehydrated alcohol, rather than the mixed solution of ethanol and water, and a commercially available product is used.

Distillation step S120: Distill the sucralose-6-ethyl ester reaction solution to remove water therein.

Ethanol and water can be azeotroped, and the water in the system can be brought out by azeotropic distillation of the ethanolic solution of the sucralose-6-ethyl ester containing water. In order to avoid the occurrence of hydrolysis side reactions, the present application is relatively The technology adds a distillation step to remove a small amount of water in the sucralose-6-ethyl ester reaction solution. One or more of the existing techniques can be used for the distillation method.

Catalysis step S130: adding an alkaline catalyst to the sucralose-6-ethyl ester reaction solution obtained in the distillation step, and reacting under preset conditions, so that the sucralose-6-ethyl ester undergoes a deacylation reaction to form trichlorosucralose-6-ethyl ester. Sucrose mixed solution.

After the distillation is completed, a basic catalyst is added to the obtained sucralose-6-ethyl ester reaction solution. In some embodiments, the basic catalyst can be a strong base, a weak base, an organic base, an inorganic base, or a Supported forms of bases such as basic anion resins.

The acyl group at the 6-position of sucralose-6-ethyl ester is removed to become a hydroxyl group, and the sucralose-6-ethyl ester is reduced to sucralose.

and impurity removal step S140: filtering the sucralose mixed solution to obtain a crude sucralose product solution.

Finally, the three-filtered sucrose mixed solution obtained above is filtered to remove the basic catalyst, and the catalyst can be recovered and reused. In the method provided by the present application, the method for removing the catalyst is very simple, and only requires conventional means such as simple filtration, which greatly saves the process cost.

By the method shown in Figure 1, the application uses ethanol as a solvent, and the ethyl acetate of the by-product is a species originally applied in the sucralose production process flow, and can be applied in the process, thereby reducing the generation of sucralose. The types of materials to be treated in the process flow significantly reduce the difficulty and cost of post-processing; and the water in the reaction system can be removed by azeotropic distillation, avoiding the occurrence of hydrolysis side reactions, and greatly reducing the content of by-product acetic acid , the product quality of sucralose is improved; and the catalyst in the present application can be recycled through simple treatment, which reduces the production cost of sucralose.

In some embodiments of the present application, in the above-mentioned preparation method of sucralose, the step of removing impurities further includes: adding an acidic cationic resin to the sucralose mixed solution, and under the condition that the sucralose mixed solution is in a neutral condition , filtered to obtain a crude product solution of sucralose.

In order to further purify the crude sucralose product solution and remove a small amount of metal cations that may remain, acidic cationic resin can be added to it, and the acidic cationic resin can exchange with metal cations and adsorb with other impurities. The sucralose mixed solution is under neutral conditions and filtered to obtain a crude product solution of sucralose with higher purity.

It should be noted that the neutral condition mentioned here is not the condition of pH=7 in the strict sense. In the range of pH=6-8, it can be considered that the sucralose mixed solution has reached the neutral condition.

Amount and source of ethanol

In the present application, the ethanol used as the solvent may be commercially available anhydrous ethanol, and in order to further remove the water therein, distillation may also be performed before use.

In some embodiments of the present application, the amount of ethanol is not limited. In other embodiments, the amount of ethanol is 5-15 mL by volume based on each gram of sucralose-6-ethyl ester. If the consumption of ethanol is less than 5mL by volume, then the consumption of ethanol is insufficient, and the sucralose-6-ethyl ester cannot be completely dissolved; if the consumption of ethanol is greater than 15mL by volume, then the consumption of ethanol is excessive, causing unnecessary waste. , and can not bring other beneficial effects, and will increase the disposal amount of solvent removal in the subsequent sucralose crystallization process.

Distillation conditions

In some embodiments of the present application, the distillation method and distillation conditions are not limited. In other embodiments, in the distillation step, the distillation is atmospheric distillation, the distillation temperature is 78-110° C., and the distillation time is 0.5- 6h.

Ethanol and a small amount of water in the sucralose-6-ethyl ester solution can azeotrope. Under the condition of distillation, ethanol and water azeotrope, thereby removing the water in the sucralose-6-ethyl ester reaction solution.

In some embodiments of the present application, the distillation may be atmospheric distillation, the distillation temperature may be 78-110° C., and the distillation time may be 0.5-6 h. If the distillation temperature is less than 78° and the distillation time is less than 0.5h, the distillation temperature is too low and the distillation time is too short to effectively remove the moisture in the sucralose-6-ethyl ester reaction solution; if the distillation temperature is greater than 110°, the distillation time More than 6h, the distillation temperature is too high, the distillation time is too long, and the solvent ethanol will be taken away in large quantities, which cannot provide a sufficient solvent environment for the subsequent deacylation reaction of sucralose-6-ethyl ester, and the excessively high temperature and overheating. Long distillation times may cause decomposition of the reactants.

In some embodiments of the present application, in order to suppress the occurrence of hydrolysis side reactions, in the distillation step, the moisture content in the sucralose-6-ethyl ester reaction solution may be distilled to ≤5000 ppm, preferably ≤2000 ppm.

Type and dosage of basic catalyst

In some embodiments of the present application, the type of the basic catalyst is not limited. In other embodiments, the basic catalyst is sodium hydroxide and/or potassium hydroxide. Sodium hydroxide and/or potassium hydroxide are cheap and easy to obtain, and have very low solubility in the sucralose-6-ethyl ester reaction solution. After the reaction is completed, it can be separated from the reaction system by a simple filtration process, and Recycling reduces the production cost of sucralose.

In some embodiments of the present application, the amount of the basic catalyst is not limited. In other embodiments, the amount of basic catalyst is based on per gram of sucralose-6-ethyl ester by mass. 0.01～0.1g. If the amount of the basic catalyst is less than 0.01 g by mass, the amount of the catalyst is too small to catalyze the complete deacylation of sucralose-6-ethyl ester in a short time; if the amount of the basic catalyst is greater than 0.1 g by mass g, the amount of catalyst is too much, there is no obvious benefit, and the alkaline environment of the reaction solution is too strong, which may lead to unnecessary side reactions.

preset conditions

In some embodiments of the present application, in the catalytic step, the preset conditions are not limited, as long as the deacylation reaction can be achieved; in other embodiments, the preset conditions are: under stirring conditions, The reaction temperature was set to 10-60°C, and the reaction time was set to 0.5-24 h. Among them, stirring helps the reactant and the catalyst to mix uniformly, so that the reaction proceeds smoothly. If the reaction temperature is less than 10°C and the reaction time is less than 0.5h, the reaction conditions are too mild, the time is too short, and the deacylation reaction cannot proceed completely; if the reaction temperature is higher than 60°C and the reaction time is longer than 6h, the reaction conditions are too intense, And if the time is too long, it may cause unnecessary side effects.

Types and sources of sucralose-6-ethyl ester

Sucralose-6-ethyl ester can be obtained by using the existing single-group protection method to produce sucralose, or can be a commercially available product, which is not limited in this application.

Reaction formula (3) shows the reaction process of the preparation method of sucralose according to another embodiment of the present application, as can be seen from reaction formula (3), sucralose-6-ethyl ester contains a small amount of water, Sucralose-6-ethyl ester is dissolved in ethanol and distilled, and water and ethanol are azeotroped to remove a small amount of water to suppress the side reaction of hydrolysis. Deacylation is carried out by adding sodium hydroxide and/or potassium hydroxide as a catalyst to generate a mixed solution of sucralose, and the mixed solution of sucralose includes sodium hydroxide and/or potassium hydroxide and the by-products ethyl acetate, acetic acid Ethyl ester is a material type in the original sucralose production process, which can be recycled and applied, so after simple filtration, the crude sucralose product solution can be obtained.

Reaction (3)

Measurement method

The test instruments and test conditions of the high performance liquid chromatography involved in this application are as follows:

Shimadzu high performance liquid chromatograph, equipped with RID-10A differential refractive index detection, LC-10ADVP high pressure pump, CTO-10ASVP incubator; chromatographic column: Agilent XDB C18 column (250mm×4.6mm, 5μm); mobile phase: methanol- 0.125% dipotassium hydrogen phosphate aqueous solution (4:6); column temperature: 30°C; flow rate: 1.0 mL/min. Among them, methanol (chromatographic grade), dipotassium hydrogen phosphate (analytical grade), ultrapure water, and other standard substances are required, and the content is measured by the external standard method.

In this application, high performance liquid chromatography can be used to determine the contents of sucralose-6-ethyl ester, acetic acid and sucralose, which will not be repeated in each embodiment.

The determination of water content uses Karl Fischer method, please refer to the prior art, and will not be repeated in each embodiment.

Yield calculation method:

In each embodiment and comparative example, the judging criterion for the complete conversion of sucralose-6-ethyl ester is: sampling the reaction system, and in the high-performance liquid chromatography of the measured sample, excluding the solvent peak, it is displayed on the chromatogram. Among the remaining other species, the relative peak area of sucralose-6-ethyl ester was ≤ 0.5%.

The reaction yield is: the percentage of the actual yield of sucralose measured by the external standard method of high performance liquid chromatography to the theoretical yield of the reaction.

The crude product solution of sucralose obtained by any of the above-mentioned methods can obtain a crude product with less acetic acid content compared to the prior art, and reduce or even avoid the negative impact of acetic acid. In some embodiments of the present application , the acetic acid content in the obtained crude product solution of sucralose is less than or equal to 230ppm, or even lower.

Further, in some embodiments of the present application, the above method may further include: a refining step: crystallizing and purifying the crude sucralose product solution to obtain sucralose crystals.

The obtained crude product solution of sucralose is purified by crystallization to obtain high-purity sucralose crystals. Crystallization can be achieved by one or a combination of methods in the prior art.

Example 1

In a three-necked round-bottomed flask with a volume of 1000 ml, add 100 g of sucralose-6-ethyl ester, add 500 ml of ethanol, and fully dissolve to form a homogeneous solution. The flask was equipped with a distillation device and a mechanical stirring device, the stirring was turned on, heated to 80° C. and maintained for 4 hours. After about 100 ml of distillate was distilled, the water content of the reaction system was determined to be 3500 ppm. Cool the reaction system to 25°C, add 1 g of NaOH to the reaction solution, maintain the reaction at 25°C for 24 hours, determine the residual sucralose-6-ethyl ester by high performance liquid chromatography ≤ 0.5% (relative peak area), stop stirring . The catalyst is removed by filtration, the obtained filtrate contains the crude sucralose product, and the acetic acid content in the filtrate measured by high performance liquid chromatography is below the detection limit. Further, the sucralose product can be further purified according to conventional methods, and the obtained sucralose There is no acidic odor in the finished product. The yield of sucralose from the deacetylation reaction of sucralose-6-ethyl ester determined by high performance liquid chromatography was 90%.

Example 2

In a three-necked round-bottomed flask with a volume of 1000 ml, add 100 g of sucralose-6-ethyl ester, add 600 ml of ethanol, and fully dissolve to form a homogeneous solution. The flask was equipped with a distillation device and a mechanical stirring device, the stirring was turned on, heated to 90° C. and maintained for 2 hours. After about 200 ml of distillate was distilled, the water content of the reaction system was determined to be 3000 ppm. Cool the reaction system to 40°C, add 2 g of KOH to the reaction solution, maintain the reaction at 40°C for 12 hours, determine the residual sucralose-6-ethyl ester by high performance liquid chromatography ≤ 0.5% (relative peak area), stop stirring . The catalyst is removed by filtration, the obtained filtrate contains the crude sucralose product, and the acetic acid content in the filtrate measured by high performance liquid chromatography is below the detection limit. Further, the sucralose product can be further purified according to conventional methods, and the obtained sucralose There is no acidic odor in the finished product. The yield of sucralose by deacetylation of sucralose-6-ethyl ester determined by high performance liquid chromatography was 93%.

Example 3

In a three-necked round-bottomed flask with a volume of 1000 ml, add 100 g of sucralose-6-ethyl ester, add 600 ml of ethanol, and fully dissolve to form a homogeneous solution. The flask was equipped with a distillation device and a mechanical stirring device, the stirring was turned on, heated to 105° C. and maintained for 1 hour. After about 200 ml of distillate was distilled, the water content of the reaction system was determined to be 2000 ppm. Cool the reaction system to 50°C, add 10 grams of NaOH to the reaction solution, maintain the reaction at 50°C for 1 hour, determine the residual sucralose-6-ethyl ester by high performance liquid chromatography ≤ 0.5% (relative peak area), stop stirring . Filter to remove the catalyst, then use a small amount of acidic cation resin to adjust the pH of the filtrate to neutral, filter to remove the resin, the obtained filtrate contains the crude product of sucralose, and the acetic acid content in the filtrate determined by high performance liquid chromatography is below the detection limit, further, The sucralose product can be further purified according to conventional methods, and the obtained sucralose finished product has no acidic odor. The yield of sucralose from the deacetylation reaction of sucralose-6-ethyl ester determined by high performance liquid chromatography was 85%.

Example 4

In a three-necked round-bottomed flask with a volume of 2000 ml, add 100 grams of sucralose-6-ethyl ester, add 1000 ml of ethanol, and fully dissolve to form a homogeneous solution. The flask was equipped with a distillation device and a mechanical stirring device, the stirring was turned on, heated to 80° C. and maintained for 6 hours. After about 400 ml of distillate was distilled, the water content of the reaction system was determined to be 1000 ppm. Cool the reaction system to 25°C, add 5 grams of NaOH to the reaction solution, maintain the reaction at 25°C for 2 hours, determine the residual sucralose-6-ethyl ester by high performance liquid chromatography ≤ 0.5% (relative peak area), stop stirring . Filter to remove the catalyst, then use a small amount of acidic cation resin to adjust the pH of the filtrate to neutral, filter to remove the resin, the obtained filtrate contains the crude product of sucralose, and the acetic acid content in the filtrate determined by high performance liquid chromatography is below the detection limit, further, The sucralose product can be further purified according to conventional methods, and the obtained sucralose finished product has no acidic odor. The yield of sucralose from the deacetylation of sucralose-6-ethyl ester was determined to be 89% by high performance liquid chromatography.

Embodiment 5 (recovery catalyst is applied mechanically)

In a three-necked round-bottomed flask with a volume of 2000 ml, add 100 grams of sucralose-6-ethyl ester, add 1000 ml of ethanol, and fully dissolve to form a homogeneous solution. The flask was equipped with a distillation device and a mechanical stirring device, the stirring was turned on, heated to 80° C. and maintained for 6 hours. After about 400 ml of distillate was distilled, the water content of the reaction system was determined to be 1000 ppm. The reaction system was cooled to 25 ° C, the catalyst recovered in Example 4 was added to the reaction solution, and after maintaining the reaction at 25 ° C for 4 hours, the residual sucralose-6-ethyl ester was determined by high performance liquid chromatography.≤0.5% (relative peak area ), stop stirring. Filter to remove the catalyst, then use a small amount of acidic cation resin to adjust the pH of the filtrate to neutral, filter to remove the resin, the obtained filtrate contains the crude product of sucralose, and the acetic acid content in the filtrate determined by high performance liquid chromatography is below the detection limit, further, The sucralose product can be further purified according to conventional methods, and the obtained sucralose finished product has no acidic odor. The yield of sucralose produced by deacetylation of sucralose-6-ethyl ester was determined by high performance liquid chromatography, and the yield was 84%.

Comparative Example 1 (Deacetylation of MeONa/MeOH System)

In a three-necked round-bottomed flask with a volume of 1000 ml, add 100 g of sucralose-6-ethyl ester, add 300 ml of methanol, fully dissolve to form a homogeneous solution, and add 2 g of sodium methoxide to the solution. Equipped with a mechanical stirring device on the flask, turned on stirring, and maintained the reaction at 25° C. for 6 hours. The residual sucralose-6-ethyl ester was determined by high performance liquid chromatography ≤0.5% (relative peak area), and the stirring was stopped. An appropriate amount of acidic cationic resin was added to the reaction solution, and stirring was maintained at low speed until the pH of the reaction solution was 7. The resin is removed by filtration, the obtained filtrate contains the crude product of sucralose, and the filtrate is determined by high performance liquid chromatography to contain acetic acid, and the content is higher than 230ppm. Further, the sucralose product can be further purified according to conventional methods, and the obtained sucralose The finished product has a distinct acidic odor. The yield of sucralose from the deacetylation of sucralose-6-ethyl ester was determined to be 89% by high performance liquid chromatography.

As can be seen from Examples 1 to 5 and Comparative Example 1, using the method of the present application and using ethanol as a solvent, the water in the sucralose-6-ethyl ester can be removed by distillation and azeotropy, and the side reaction of hydrolysis can be suppressed, so that the The acetic acid content in the product is extremely low, the obtained sucralose finished product has no acidic odor, and the catalyst can be recycled and reused through simple filtration, thereby reducing the generation cost of the sucralose.

To sum up, the beneficial effect of the present application is that the present application uses ethanol as a solvent, and the generated ethyl acetate is a species originally used in the production process of sucralose, and can be applied in the process, thereby reducing three The types of materials to be treated in the production process of chlorosucrose significantly reduce the difficulty and cost of post-treatment; and the water in the reaction system can be removed by azeotropic distillation, avoiding the occurrence of hydrolysis side reactions, and greatly reducing by-products The content of acetic acid improves the product quality of sucralose; and the catalyst in the present application can be recycled through simple treatment, thereby reducing the production cost of sucralose.

The above descriptions are only specific implementations of the present application, and those skilled in the art can make other improvements or modifications on the basis of the above-mentioned embodiments under the above teachings of the present application. Those skilled in the art should understand that the above-mentioned specific description is only to better explain the purpose of the present application, and the protection scope of the present application should be subject to the protection scope of the claims.

Furthermore, those skilled in the art will appreciate that although some of the embodiments described herein include certain features, but not others, included in other embodiments, that combinations of features of different embodiments are intended to be within the scope of the present application within and form different embodiments. For example, in the following claims, any of the claimed embodiments may be used in any combination.

Claims (10)

A preparation method of sucralose, characterized in that, comprising: Dissolving step: dissolving sucralose-6-ethyl ester in ethanol to form a sucralose-6-ethyl ester reaction solution; Distillation step: distilling the sucralose-6-ethyl ester reaction solution to remove moisture therein; Catalysis step: adding an alkaline catalyst to the sucralose-6-ethyl ester reaction solution obtained in the distillation step, and reacting under preset conditions, so that the sucralose-6-ethyl ester undergoes a deacylation reaction , forming a mixed solution of sucralose; and The step of removing impurities: filtering the mixed solution of sucralose to obtain a crude product solution of sucralose. The method according to claim 1, wherein the step of removing impurities further comprises: The acidic cationic resin is added to the sucralose mixed solution, and the sucralose mixed solution is filtered under the condition that the sucralose mixed solution is neutral to obtain a sucralose crude product solution. The method according to claim 1, wherein the consumption of the ethanol is 5-15 mL by volume based on per gram of sucralose-6-ethyl ester. The method according to claim 1, characterized in that, in the distillation step, the distillation is atmospheric distillation, the distillation temperature is 78-110°C, and the distillation time is 0.5-6h. The method according to claim 1, wherein, in the distillation step, the water content in the sucralose-6-ethyl ester reaction solution is distilled to ≤5000ppm, preferably ≤2000ppm. The method according to claim 1, wherein the basic catalyst is sodium hydroxide and/or potassium hydroxide; On the basis of sucralose-6-ethyl ester per gram, the amount of the basic catalyst is recorded as 0.01-0.1 g by mass. The method according to claim 1, wherein, in the catalysis step, the preset conditions are: under stirring, the reaction temperature is set to 10-60°C, and the reaction time is set to 0.5-24h. The method according to any one of claims 1-7, further comprising: Crystallization and purification step: crystallization and purification of the crude sucralose product solution to obtain sucralose crystals. A sucralose crude product solution, prepared by the method according to any one of claims 1 to 7, wherein the acetic acid content is less than or equal to 230 ppm. A kind of sucralose, which is obtained by adopting the sucralose crude product solution crystallization and refining in claim 9.

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