CN112805291A - Preparation method of sucralose, crude product solution and sucralose - Google Patents

Preparation method of sucralose, crude product solution and sucralose Download PDF

Info

Publication number
CN112805291A
CN112805291A CN202080004024.8A CN202080004024A CN112805291A CN 112805291 A CN112805291 A CN 112805291A CN 202080004024 A CN202080004024 A CN 202080004024A CN 112805291 A CN112805291 A CN 112805291A
Authority
CN
China
Prior art keywords
sucralose
ethyl ester
reaction
solution
crude
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Pending
Application number
CN202080004024.8A
Other languages
Chinese (zh)
Inventor
张正颂
赵金刚
钱庆喜
杨志健
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Anhui Jinhe Industrial Co Ltd
Original Assignee
Anhui Jinhe Industrial Co Ltd
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Anhui Jinhe Industrial Co Ltd filed Critical Anhui Jinhe Industrial Co Ltd
Priority to CN2020141528 priority Critical
Publication of CN112805291A publication Critical patent/CN112805291A/en
Pending legal-status Critical Current

Links

Classifications

    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07HSUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
    • C07H1/00Processes for the preparation of sugar derivatives
    • AHUMAN NECESSITIES
    • A23FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23LFOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
    • A23L27/00Spices; Flavouring agents or condiments; Artificial sweetening agents; Table salts; Dietetic salt substitutes; Preparation or treatment thereof
    • A23L27/30Artificial sweetening agents
    • A23L27/33Artificial sweetening agents containing sugars or derivatives
    • A23L27/37Halogenated sugars
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07HSUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
    • C07H1/00Processes for the preparation of sugar derivatives
    • C07H1/06Separation; Purification
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07HSUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
    • C07H5/00Compounds containing saccharide radicals in which the hetero bonds to oxygen have been replaced by the same number of hetero bonds to halogen, nitrogen, sulfur, selenium, or tellurium
    • C07H5/02Compounds containing saccharide radicals in which the hetero bonds to oxygen have been replaced by the same number of hetero bonds to halogen, nitrogen, sulfur, selenium, or tellurium to halogen
    • AHUMAN NECESSITIES
    • A23FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23VINDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES
    • A23V2002/00Food compositions, function of food ingredients or processes for food or foodstuffs

Abstract

The application provides a preparation method of sucralose, a crude product solution and sucralose, wherein the preparation method comprises the following steps: dissolving sucralose-6-ethyl ester in methanol to form a sucralose-6-ethyl ester reaction solution; adding calcium oxide into the sucralose-6-ethyl ester reaction solution, and reacting under a preset condition to perform deacylation reaction on the sucralose-6-ethyl ester to form a sucralose mixed solution; and filtering the sucralose mixed solution to obtain a sucralose crude product solution. According to the method, calcium oxide is used as a catalyst, when the deacylation reaction of the sucralose-6-ethyl ester is catalyzed efficiently and reliably, the calcium oxide can be removed and recycled through simple filtration, the consumption of the catalyst is reduced, and the production cost of the sucralose is reduced to a great extent; in addition, the generation of hydrolysis side reaction is inhibited, so that the content of acetic acid in the final product is reduced, and the product quality is obviously improved.

Description

Preparation method of sucralose, crude product solution and sucralose
Technical Field
The invention belongs to the technical field of fine chemical engineering, and particularly relates to a preparation method of sucralose, a crude product solution and sucralose.
Background
Sucralose belongs to a new generation sweetener, has the advantages of high sweetness, no calorie, good stability, high safety and the like, and has very wide market prospect. The process for synthesizing sucralose has been a major advance since the advent of sucralose. So far, the mainstream synthesis process is a single-group protection method: the 6-hydroxy group with the highest sucrose activity is selectively protected, and is usually in the form of ethyl ester, namely sucrose-6-ethyl ester is generated, the three hydroxy groups at the 4, 1 'and 6' positions of the sucrose-6-ethyl ester are subjected to selective chlorination reaction to generate sucralose-6-ethyl ester, and the sucralose-6-ethyl ester is deacetylated to generate sucralose.
For the deacetylation step, the existing process basically adopts catalytic amount of sodium methoxide (MeONa) as catalyst, and carries out alcoholysis in methanol (MeOH) to remove acetyl, generate sucralose and byproduct methyl acetate, etc. The adoption of the MeONa/MeOH catalytic system has the advantages of mild conditions, rapid reaction, high yield and the like, but also has certain disadvantages, such as the MeONa is relatively expensive and can not be recycled, thereby increasing the production cost; the generated methyl acetate is used as a byproduct, can not be applied to the process flow, and increases the types of materials needing to be operated in the process flow.
In addition, as sucralose-6-ethyl ester used as a reaction raw material often contains a small amount of moisture, hydrolysis reaction exists as a side reaction, and the hydrolysis reaction competes with alcoholysis main reaction, so that not only is a large amount of catalyst MeONa wasted, but also sodium acetate is generated, acetic acid is generated through acid cation resin exchange, and the acetic acid remains in a sucralose product, so that the product has obvious acidic odor, and the product quality is seriously influenced.
Therefore, the process for synthesizing the sucralose by removing the acyl group from the sucralose-6-ethyl ester has great improvement and promotion space. It should be noted that the statements herein merely provide background information related to the present application and may not necessarily constitute prior art.
Disclosure of Invention
In view of the above, the present application has been developed to provide a method of preparing sucralose, a crude product solution, and sucralose that overcome or at least partially solve the above problems.
According to one aspect of the present application, there is provided a method for preparing sucralose, comprising:
a dissolving step: dissolving sucralose-6-ethyl ester in methanol to form a sucralose-6-ethyl ester reaction solution;
a catalysis step: adding calcium oxide into the sucralose-6-ethyl ester reaction solution, and reacting under a preset condition to perform deacylation reaction on the sucralose-6-ethyl ester to form a sucralose mixed solution;
impurity removal: and filtering the sucralose mixed solution to obtain a sucralose crude product solution.
According to another aspect of the present application, a sucralose crude product solution is provided, which is prepared by the above preparation method, wherein the content of acetic acid is less than or equal to 230 ppm.
According to still another aspect of the present application, there is provided a sucralose obtained by crystallization and purification of the above crude sucralose solution.
To sum up, the beneficial effect of this application lies in: calcium oxide is used as a catalyst, and can be removed and recycled through simple filtration while efficiently and reliably catalyzing the deacylation reaction of the sucralose-6-ethyl ester, so that the consumption of the catalyst is reduced, and the production cost of the sucralose is greatly reduced; in addition, the calcium oxide can consume the moisture in the sucralose-6-ethyl ester, inhibit the occurrence of hydrolysis side reaction, reduce the content of acetic acid in the final product and obviously improve the product quality.
The foregoing description is only an overview of the technical solutions of the present application, and the present application can be implemented according to the content of the description in order to make the technical means of the present application more clearly understood, and the following detailed description of the present application is given in order to make the above and other objects, features, and advantages of the present application more clearly understandable.
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 only for purposes of illustrating the preferred embodiments and are not to be construed as limiting the application. Also, like reference numerals are used to refer to like parts throughout the drawings. In the drawings:
fig. 1 shows a schematic flow diagram of a method of making sucralose according to one embodiment of the present application.
Detailed Description
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 to the embodiments set forth herein. Rather, these embodiments are provided so that this disclosure will be thorough and complete, and will fully convey the scope of the disclosure to those skilled in the art.
Although the classical combination of the system MeONa/MeOH (MeONa/MeOH stands for both), in particular MeONa as catalyst and MeOH as solvent, is widely used for deacetylation of carbohydrates (i.e.Zemplein reaction), however, the MeONa/MeOH system as a catalyst suffers from a number of disadvantages, for example, since sucralose-6-ethyl ester as a reaction raw material often contains a small amount of moisture, in the presence of MeONa, hydrolysis of sucralose-6-ethyl ester is caused, the hydrolysis reaction is taken as a side reaction, competing with the main alcoholysis reaction, the catalyst MeONa is consumed in a large amount to generate sodium acetate, the sodium acetate is exchanged by acidic cation resin to generate acetic acid, acetic acid is difficult to remove due to high boiling point and is easy to remain in the final sucralose product, so that the product has obvious acidic odor and the quality of the product is seriously influenced. And because the hydrolysis reaction and the alcoholysis reaction compete, a large amount of catalyst is consumed, and the production cost of the sucralose is increased.
In order to solve the problems, calcium oxide is used as a catalyst, the calcium oxide can efficiently and reliably catalyze deacetylation reaction, the solubility of the calcium oxide in a reaction system is very low, most of the calcium oxide can be removed and recycled through simple filtration, the consumption of the catalyst is reduced, in addition, the calcium oxide can very easily react with water, and water in raw materials is consumed, so that acetic acid generated by hydrolysis side reaction in the deacetylation process is avoided, acetic acid residue cannot be generated in a final sucralose product, the product quality is greatly improved, and the calcium hydroxide generated by the reaction of the calcium oxide with the water can also catalyze the deacetylation reaction.
Fig. 1 shows a schematic flow diagram of a method of making sucralose according to one embodiment of the present application, comprising:
a dissolving step S110: dissolving the sucralose-6-ethyl ester in methanol to form a sucralose-6-ethyl ester reaction solution.
First, sucralose-6-ethyl ester is dissolved in methanol, and then the sucralose-6-ethyl ester and the methanol can form a homogeneous mixture by means of stirring and the like.
Catalytic step S120: adding calcium oxide into the sucralose-6-ethyl ester reaction solution, and reacting under preset conditions to perform deacylation reaction on the sucralose-6-ethyl ester to form a sucralose mixed solution.
At present, the most widely used method for preparing sucralose is a single-group protection method, taking sucralose-6-ethyl ester as an example, and the reaction process is shown as the reaction formula (1).
Reaction formula (1)
From the reaction formula (1), it can be seen that the highest activity of sucrose is 6-hydroxy, and in the single-group protection method, it is protected by using an acylation reagent such as acetic anhydride, specifically, taking acetic anhydride as an example, sucrose acetic anhydride is subjected to esterification reaction to generate sucrose-6-ethyl ester, after the selective chlorination reaction of three hydroxy groups at 4, 1 ', 6' positions is completed, the deacylation reaction is performed to finally generate sucralose, and the 6-hydroxy is protected to prevent the hydroxy group at 6 position from being substituted by chlorine atom.
The method mainly aims at the deacetylation step, and in the prior art, sodium methoxide is generally used as a catalyst, and methanol is used as a solvent for deacetylation reaction. Since a small amount of water is usually present in the sucrose-6-ethyl ester solution, during deacylation, a hydrolysis side reaction occurs, which competes with the alcoholysis main reaction, as shown in equation (2).
Reaction type (2)
In the process of adopting the MeONa/MeOH catalytic system in the prior art shown in the reaction formula (2), competition exists between alcoholysis main reaction and hydrolysis side reaction, the hydrolysis reaction consumes the catalyst MeONa and generates sodium acetate, the sodium acetate generates acetic acid through acidic cation resin exchange, and the acetic acid remains in the final product, so that the color and the taste of the sucralose are affected.
In view of the above situation, in the zemplian reaction system, MeONa can be replaced by many different types of bases, such as strong base, weak base, organic base or inorganic base, and also include base in immobilized form such as basic anion resin, which can catalyze the deacetylation process very well. Calcium oxide is used as a catalyst, and on one hand, the calcium oxide can efficiently and reliably catalyze the deacylation reaction of the sucralose-6-ethyl ester; on the other hand, calcium oxide reacts with water in the sucralose-6-ethyl ester to generate calcium hydroxide, namely, hydrolysis side reaction is inhibited, and the generated calcium hydroxide can also be used as a catalyst to catalyze the deacylation reaction of the sucralose-6-ethyl ester.
Through the catalysis step, the acyl on the 6-position of the sucralose-6-ethyl ester is removed to become hydroxyl, and the sucralose-6-ethyl ester is reduced into sucralose.
And an impurity removal step S130: and filtering the sucralose mixed solution to obtain a sucralose crude product solution.
The solubility of calcium oxide in a reaction system is very low, so that the catalyst can be removed by filtering the obtained three-filter sucrose mixed solution.
By the method shown in the figure 1, calcium oxide is used as a catalyst, and can be removed and recycled through simple filtration while efficiently and reliably catalyzing the deacylation reaction of the sucralose-6-ethyl ester, so that the consumption of the catalyst is reduced, and the production cost of the sucralose is greatly reduced; in addition, the calcium oxide can consume the moisture in the sucralose-6-ethyl ester, inhibit the occurrence of hydrolysis side reaction, reduce the content of acetic acid in the final product and obviously improve the product quality.
In some embodiments of the present application, in the above method for preparing sucralose, the step of removing impurities further comprises: and adding acidic cation resin into the sucralose mixed solution, and filtering under the condition that the sucralose mixed solution is neutral to obtain a sucralose crude product solution.
In order to obtain a further purified sucralose crude product solution, an acidic cation resin can be added, the acidic cation resin can remove a small amount of calcium ions which can be dissolved in the system and other impurities which can exist by adsorption, and then the filtration is carried out under the neutral condition of the system, and the obtained filtrate is the sucralose crude product solution with higher purity.
It should be noted that the neutral condition is not strictly a condition of pH 7, and it is considered that the sucralose mixed solution has reached a neutral condition in a range of pH 6 to 8.
In some embodiments of the present application, the method for preparing sucralose further comprises: and (3) catalyst recovery: and (4) recovering and reusing the catalyst obtained by filtering in the impurity removal step.
In the application, a small amount of the catalyst can be mixed with water to produce calcium hydroxide in the first process, so that most of the recovered catalyst is calcium oxide, and a small amount of calcium hydroxide is also included, and both the calcium oxide and the calcium hydroxide can catalyze the deacylation reaction of the sucralose-6-ethyl ester.
In some embodiments of the present application, the method for preparing sucralose further comprises: and a refining step, wherein the crude sucralose product solution is purified and refined to improve the purity of sucralose.
To further increase the purity of the sucralose, the sucralose may be purified by one or a combination of several of the prior art techniques.
Sources of drugs
In the present application, if not specifically stated, the conventional drugs may be commercially available products, which are not described in detail herein.
The amount and source of methanol
In some embodiments of the present application, the amount of methanol is not limited, and in other embodiments, the amount of methanol is 3 to 10mL per gram of sucralose-6-ethyl ester; if the dosage of the methanol is less than 3mL by volume, the dosage of the methanol is insufficient, and the sucralose-6-ethyl ester cannot be completely dissolved; if the amount of the methanol is more than 10mL by volume, the amount of the methanol is excessive, unnecessary waste is caused, other beneficial effects cannot be brought, and the solvent removal amount of the subsequent sucralose crystallization process is increased.
The amount of calcium oxide
In some embodiments of the present application, the amount of the catalyst is not limited, and in other embodiments, the amount of the calcium oxide is 0.5 to 1.0g by mass per gram of sucralose-6-ethyl ester. If the amount of the calcium oxide is less than 0.5g by mass, the amount of the catalyst is too small to rapidly catalyze the sucralose-6-ethyl ester to perform complete deacylation in a short time; if the amount of the calcium oxide is more than 1.0g by mass, the amount of the catalyst is too large, unnecessary waste is caused, and other beneficial effects cannot be brought about, and moreover, the alkaline environment of the reaction solution is too strong, and unnecessary side reactions may be caused.
Preset conditions
In some embodiments of the present application, in the catalyzing step, the preset conditions are not limited, and the deacylation reaction may be performed; in other embodiments, the preset conditions are: under the condition of stirring, the reaction temperature is set to be 10-60 ℃, and the reaction time is set to be 0.5-24 h. Wherein, stirring helps reactant and catalyst reaction misce bene, makes the reaction go on smoothly. If the reaction temperature is less than 10 ℃ and the reaction time is less than 0.5h, the reaction conditions are too mild, the reaction time is too short, and the deacylation reaction cannot be completely carried out; if the reaction temperature is greater than 60 ℃ and the reaction time is greater than 6 hours, the reaction conditions are too severe and too long, there is no significant benefit, and unnecessary side reactions may be caused.
Sources of sucralose-6-ethyl ester
The sucralose-6-ethyl ester can be obtained in the process of producing sucralose by adopting the existing single group protection method, and can also be a commercially available product.
Reaction formula (3) shows the reaction process of the preparation method of sucralose according to another embodiment of the present application, and it can be seen from reaction formula (3) that sucralose-6-ethyl ester contains a small amount of water, sucralose-6-ethyl ester is dissolved in methanol, then calcium oxide is added as a catalyst to perform deacylation reaction, in this process, calcium oxide reacts with a small amount of water in sucralose-6-ethyl ester to generate calcium hydroxide, and calcium oxide and calcium hydroxide simultaneously catalyze the deacylation reaction of sucralose-6-ethyl ester to generate a sucralose mixed solution.
Reaction type (3)
Measurement means
The instrumentation and test conditions for high performance liquid chromatography referred to in this application are as follows:
a Japanese Shimadzu high performance liquid chromatograph, which is matched with RID-10A refractive index detection, an LC-10ADVP high-pressure pump and a CTO-10ASVP constant temperature box; a chromatographic column: agilent XDB C18 column (250 mm. times.4.6 mm, 5 μm); mobile phase: methanol-0.125% aqueous dipotassium hydrogen phosphate (4: 6); column temperature: 30 ℃; flow rate: 1.0 mL/min. Wherein, methanol (chromatographic purity), dipotassium hydrogen phosphate (analytical purity), ultrapure water and other standard substances are needed, and the content is measured by an external standard method.
In the present application, high performance liquid chromatography can be used to determine the content of sucralose-6-ethyl ester, acetic acid and sucralose, and is not described in detail in each example.
The determination of the water content is performed by karl fischer method, please refer to the prior art, and is not described in detail in each embodiment.
The calculation method of the yield comprises the following steps:
in each example and comparative example, the judgment criteria for complete conversion of sucralose-6-ethyl ester are as follows: sampling the reaction system, and measuring the high performance liquid chromatography of the sampled product, wherein the relative peak area of the sucralose-6-ethyl ester in the rest other species displayed on the chromatogram is less than or equal to 0.5 percent, except the solvent peak.
The reaction yield was: and determining the percentage of the actual yield of the sucralose to the theoretical yield of the reaction by using a high performance liquid chromatography external standard method.
Compared with the prior art, the crude product solution of sucralose obtained by any one of the methods can obtain a crude product with less acetic acid content, and reduce or even avoid the negative effects caused by acetic acid, in some embodiments of the present application, the content of acetic acid in the obtained crude product solution of sucralose is less than or equal to 230ppm, or even lower.
And crystallizing and refining the obtained crude product solution of the sucralose to obtain high-purity sucralose crystals. The crystallization refinement can be achieved by one or a combination of several methods in the prior art.
Example 1
100 g of sucralose-6-ethyl ester and 300 ml of methanol are added into a three-neck round-bottom flask with the volume of 1000 ml, and are fully dissolved to form a homogeneous solution, and 5g of calcium oxide is added into the solution. A mechanical stirring device is arranged on a flask, stirring is started, reaction is carried out for 24 hours at 25 ℃, then the high performance liquid chromatography is used for measuring that the residual of the sucralose-6-ethyl ester is less than or equal to 0.5 percent (relative peak area), and the stirring is stopped. And (3) filtering to remove the catalyst, wherein the obtained filtrate contains a sucralose crude product, and the content of acetic acid in the filtrate is determined to be below the detection limit by high performance liquid chromatography. The yield of sucralose generated by the deacetylation reaction of sucralose-6-ethyl ester determined by high performance liquid chromatography is 85%.
Example 2
100 g of sucralose-6-ethyl ester and 500 ml of methanol are added into a three-neck round-bottom flask with the volume of 1000 ml, and are fully dissolved to form a homogeneous solution, and 20 g of calcium oxide is added into the solution. A mechanical stirring device is arranged on a flask, stirring is started, after reaction is carried out for 6 hours at 40 ℃, high performance liquid chromatography shows that the residual of sucralose-6-ethyl ester is less than or equal to 0.5 percent (relative peak area), and stirring is stopped. Filtering to remove resin, wherein the obtained filtrate contains a sucralose crude product, and the content of acetic acid in the filtrate is determined to be below the detection limit by high performance liquid chromatography. The yield of sucralose generated by the deacetylation reaction of sucralose-6-ethyl ester determined by high performance liquid chromatography is 88%.
Example 3
100 g of sucralose-6-ethyl ester and 500 ml of methanol are added into a three-neck round-bottom flask with the volume of 1000 ml, and are fully dissolved to form a homogeneous solution, and 50 g of calcium oxide is added into the solution. A mechanical stirring device is arranged on a flask, after the reaction is carried out for 2 hours at 25 ℃, the high performance liquid chromatography shows that the residual of the sucralose-6-ethyl ester is less than or equal to 0.5 percent (relative peak area), and the stirring is stopped. And (3) filtering to remove the catalyst, wherein the obtained filtrate contains a sucralose crude product, and the content of acetic acid in the filtrate is determined to be below the detection limit by high performance liquid chromatography. The yield of sucralose generated by the deacetylation reaction of sucralose-6-ethyl ester determined by high performance liquid chromatography was 93%.
Example 4
100 g of sucralose-6-ethyl ester and 1000 ml of methanol are added into a 2000 ml three-neck round-bottom flask, fully dissolved to form a homogeneous solution, and 100 g of calcium oxide is added into the solution. A mechanical stirring device is arranged on a flask, stirring is started, after the reaction is carried out for 1 hour at the temperature of 60 ℃, the high performance liquid chromatography shows that the residual of the sucralose-6-ethyl ester is less than or equal to 0.5 percent (relative peak area), and the stirring is stopped. Filtering to remove the catalyst, adjusting the reaction solution to be neutral by using a small amount of acidic cation resin, filtering to remove the resin, wherein the obtained filtrate contains a sucralose crude product, and the content of acetic acid in the filtrate is determined to be below the detection limit by high performance liquid chromatography. The yield of sucralose generated by the deacetylation reaction of sucralose-6-ethyl ester determined by high performance liquid chromatography is 90%.
Example 5 (recycle catalyst)
100 g of sucralose-6-ethyl ester and 1000 ml of methanol were added to a 2000 ml three-neck round-bottom flask and sufficiently dissolved to form a homogeneous solution, and the catalyst recovered in example 4 was added to the solution. A mechanical stirring device is arranged on a flask, stirring is started, after reaction is carried out for 2 hours at the temperature of 60 ℃, high performance liquid chromatography shows that the residual of the sucralose-6-ethyl ester is less than or equal to 0.5 percent (relative peak area), and stirring is stopped. Filtering to remove the catalyst, adjusting the reaction solution to be neutral by using a small amount of acidic cation resin, filtering to remove the resin, wherein the obtained filtrate contains a sucralose crude product, and the content of acetic acid in the filtrate is determined to be below the detection limit by high performance liquid chromatography. The yield of sucralose generated by the deacetylation reaction of sucralose-6-ethyl ester determined by high performance liquid chromatography is 88%.
Comparative example 1 (deacetylation of MeONa/MeOH System)
100 g of sucralose-6-ethyl ester and 300 ml of methanol are added into a three-neck round-bottom flask with the volume of 1000 ml, and are fully dissolved to form a homogeneous solution, and 2 g of sodium methoxide is added into the solution. A mechanical stirring device is arranged on a flask, stirring is started, reaction is carried out for 6 hours at 25 ℃, then the high performance liquid chromatography is used for measuring that the residual of the sucralose-6-ethyl ester is less than or equal to 0.5 percent (relative peak area), and the stirring is stopped. Adding a proper amount of acidic cation resin into the reaction solution, and keeping stirring at a low speed until the pH of the reaction solution is 7. Filtering to remove resin, wherein the obtained filtrate contains a sucralose crude product, and the content of acetic acid in the filtrate is 230ppm by high performance liquid chromatography. The used acidic cation resin can be recycled after being washed and exchanged for many times by using acid, alkali and the like. The yield of sucralose generated by the deacetylation reaction of sucralose-6-ethyl ester determined by high performance liquid chromatography is 89%.
From examples 1-5 and comparative example 1, it can be seen that, by adopting the method of the present application, calcium oxide is used as a catalyst, and the calcium oxide consumes water in sucralose-6-ethyl ester through a chemical reaction to generate calcium hydroxide, so that a hydrolysis side reaction is inhibited, the content of acetic acid in the product is extremely low, the obtained sucralose finished product has no acidic odor, and the catalyst can be recovered and reused through simple filtration, so that the generation cost of the sucralose is greatly reduced.
To sum up, the beneficial effect of this application lies in: calcium oxide is used as a catalyst, and can be removed and recycled through simple filtration while efficiently and reliably catalyzing the deacylation reaction of the sucralose-6-ethyl ester, so that the consumption of the catalyst is reduced, and the production cost of the sucralose is greatly reduced; in addition, the calcium oxide can consume the moisture in the sucralose-6-ethyl ester, inhibit the occurrence of hydrolysis side reaction, reduce the content of acetic acid in the final product and obviously improve the product quality.
While the foregoing is directed to embodiments of the present application, other modifications and variations of the present application may be devised by those skilled in the art in light of the above teachings. It should be understood by those skilled in the art that the foregoing detailed description is for the purpose of better explaining the present application, and the scope of protection of the present application shall be subject to the scope of protection of the claims.
Furthermore, those skilled in the art will appreciate that while some embodiments described herein include some features included in other embodiments, rather than other features, combinations of features of different embodiments are meant to be within the scope of the application and form different embodiments. For example, in the following claims, any of the claimed embodiments may be used in any combination.

Claims (10)

1. A method for preparing sucralose, comprising:
a dissolving step: dissolving sucralose-6-ethyl ester in methanol to form a sucralose-6-ethyl ester reaction solution;
a catalysis step: adding calcium oxide into the sucralose-6-ethyl ester reaction solution, and reacting under a preset condition to perform deacylation reaction on the sucralose-6-ethyl ester to form a sucralose mixed solution; and
impurity removal: and filtering the sucralose mixed solution to obtain a sucralose crude product solution.
2. The method of claim 1, wherein the purging step further comprises:
and adding acidic cation resin into the sucralose mixed solution, and filtering under the condition that the sucralose mixed solution is neutral to obtain a sucralose crude product solution.
3. The method of claim 1, further comprising:
and (3) catalyst recovery: and recovering and reusing the catalyst obtained by filtering in the impurity removal step.
4. The method of claim 1, further comprising:
and a refining step, wherein the sucralose crude product solution is purified and refined to improve the purity of the sucralose.
5. The method according to claim 1, wherein the amount of methanol is 3-10 mL per gram of sucralose-6-ethyl ester.
6. The method according to claim 1, wherein the calcium oxide is used in an amount of 0.5 to 1.0g by mass per g of sucralose-6-ethyl ester.
7. The method according to claim 1, characterized in that in the catalytic step, the preset conditions are: under the condition of stirring, the reaction temperature is set to be 10-60 ℃, and the reaction time is set to be 0.5-24 h.
8. The method of claim 1, further comprising:
a crystallization step: and crystallizing and purifying the sucralose crude product solution to obtain sucralose crystals.
9. A sucralose crude product solution prepared by the preparation method of any one of claims 1 to 7, wherein the content of acetic acid as a byproduct is less than or equal to 230 ppm.
10. A sucralose purified by crystallization from the crude sucralose solution of claim 9.
CN202080004024.8A 2020-12-30 2020-12-30 Preparation method of sucralose, crude product solution and sucralose Pending CN112805291A (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
CN2020141528 2020-12-30

Publications (1)

Publication Number Publication Date
CN112805291A true CN112805291A (en) 2021-05-14

Family

ID=75809238

Family Applications (1)

Application Number Title Priority Date Filing Date
CN202080004024.8A Pending CN112805291A (en) 2020-12-30 2020-12-30 Preparation method of sucralose, crude product solution and sucralose

Country Status (1)

Country Link
CN (1) CN112805291A (en)

Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN104098615A (en) * 2014-06-09 2014-10-15 华中科技大学 Method for deacylation with hydroxyl ion type alkali as catalyst
CN105859802A (en) * 2016-05-14 2016-08-17 广西科技大学 Sucralose crystallization and purification method

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN104098615A (en) * 2014-06-09 2014-10-15 华中科技大学 Method for deacylation with hydroxyl ion type alkali as catalyst
CN105859802A (en) * 2016-05-14 2016-08-17 广西科技大学 Sucralose crystallization and purification method

Similar Documents

Publication Publication Date Title
US5276181A (en) Catalytic method of hydrogenating glycerol
CN1176094C (en) Synthesis of trichlorosucrose
CN101284850B (en) Purification and crystallization process of sucralose
CN110437294A (en) A method of preparing Trenbolone acetate
CN105132513A (en) Method for preparing amoxicillin or ampicillin in full-water-phase through mode
CN106631776A (en) Green preparation process for synthesizing 12-carbon alcohol ester by double catalytic system
CN103555807B (en) Method for preparing 7-ACA (aminocephalosporanic acid) and obtaining alpha-aminoadipic acid by one-step enzymatic reaction
CN111559995A (en) Preparation process of ascorbic acid ethyl ether
CN103864859B (en) A kind of preparation method of Sucralose
CN112805291A (en) Preparation method of sucralose, crude product solution and sucralose
CN110128449A (en) 7- phenylacetyl amido -3- desacetoxycephalosporanic acid salt and its preparation method and application
CN112771059A (en) Preparation method of sucralose, crude product solution and sucralose
KR20140080748A (en) Method for producing highly pure anhydrosugar alcohols with improved yield by using purification product of waste generated from crystallization procedure
CN113151374A (en) Method for improving yield of sucrose-6-acetate synthesized by enzyme method
US6667397B2 (en) Methods of preparing disaccharide and trisaccharide C6-C12 fatty acid esters with high alpha content and materials therefrom
CN112771060A (en) Preparation method of sucralose, crude product solution and sucralose
CN102108089A (en) Preparation method of 2-deoxy-L-ribose
CN112409419A (en) Method for preparing sucralose by using sucralose-6-ethyl ester
CN109060473B (en) Preparation method of ambroxol hydrochloride impurity reference substance
CN100420697C (en) Method of preparing trichloro sucrose-6-organic acid ester
JPH1087532A (en) Production of arabinitol
CN107698643A (en) A kind of preparation method of dehydroepiandros-sterone
CN103588841B (en) The process for purification of trihydroxy-oestrin
EP1589021A1 (en) Process for producing 2-deoxyaldose compound
CN112574258A (en) Method for controlling sucralose acidity

Legal Events

Date Code Title Description
PB01 Publication
PB01 Publication
SE01 Entry into force of request for substantive examination
SE01 Entry into force of request for substantive examination