CN112409419A - Method for preparing sucralose by using sucralose-6-ethyl ester - Google Patents
Method for preparing sucralose by using sucralose-6-ethyl ester Download PDFInfo
- Publication number
- CN112409419A CN112409419A CN202011384911.0A CN202011384911A CN112409419A CN 112409419 A CN112409419 A CN 112409419A CN 202011384911 A CN202011384911 A CN 202011384911A CN 112409419 A CN112409419 A CN 112409419A
- Authority
- CN
- China
- Prior art keywords
- sucralose
- ethyl ester
- resin
- anion resin
- reaction
- 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
Links
Images
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
- C07H1/00—Processes for the preparation of sugar derivatives
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
- C07H1/00—Processes for the preparation of sugar derivatives
- C07H1/06—Separation; Purification
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
- C07H5/00—Compounds containing saccharide radicals in which the hetero bonds to oxygen have been replaced by the same number of hetero bonds to halogen, nitrogen, sulfur, selenium, or tellurium
- C07H5/02—Compounds containing saccharide radicals in which the hetero bonds to oxygen have been replaced by the same number of hetero bonds to halogen, nitrogen, sulfur, selenium, or tellurium to halogen
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Engineering & Computer Science (AREA)
- Biochemistry (AREA)
- Biotechnology (AREA)
- General Health & Medical Sciences (AREA)
- Genetics & Genomics (AREA)
- Molecular Biology (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
The invention relates to a method for preparing sucralose by sucralose-6-ethyl ester, which comprises the following steps: dissolving sucralose-6-ethyl ester in methanol, wherein the proportion of the sucralose-6-ethyl ester per gram is 3-10 ml of methanol; adding alkaline anion resin into the sucralose-6-ethyl ester solution according to the proportion of sucralose-6-ethyl ester per gram, and stirring and reacting 0.2-2 g of alkaline anion resin at the temperature of 10-60 ℃ for 0.5-24 hours; after the reaction is completed, the reaction solution is filtered to remove the basic anion resin, and a filtrate containing the sucralose crude product is obtained. The invention has the advantages that: the process of removing sodium ions by using the cationic resin is omitted, so that the material loss and the generation of waste water are reduced, and the production cost is comprehensively reduced. The basic anion resin can be simply removed by filtration and can be recovered for reuse. The alkaline anion resin can simultaneously adsorb acetic acid possibly generated in the deacetylation process, and the sour problem caused by residual acetic acid in the product is avoided.
Description
Technical Field
The invention belongs to the technical field of fine chemical engineering, and particularly relates to a method for preparing sucralose by using sucralose-6-ethyl ester.
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 (as shown in fig. 1): that is, the 6-hydroxyl with the highest sucrose activity is selectively protected, and usually in the form of acetate, namely sucrose-6-ethyl ester is generated, and the three hydroxyl at the 4/1 '/6' position 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 subjected to deacetylation protection, so that the sucralose is finally synthesized.
Among them, the existing process basically uses catalytic amount of sodium methoxide (MeONa) as catalyst for deacetylation step, and carries out alcoholysis (i.e. zemplein reaction, as shown in fig. 2) in methanol (MeOH) to deacetylate (with formation of methyl acetate), and has the advantages of mild conditions, rapid reaction and high yield. However, the deacetylation process using the MeONa/MeOH system has obvious disadvantages, such as the MeONa serving as the catalyst cannot be recycled, sodium ions need to be exchanged by using acidic cation resin for removal, the regeneration of the cation resin needs to consume a large amount of acid and alkali and generate a large amount of wastewater, and the like, which causes the problems of complicated operation steps, large material consumption, more generated wastewater and the like in production. More critically, the inventors found that the presence of MeONa leads to hydrolysis of sucralose-6-ethyl ester (as shown in fig. 2), since sucralose-6-ethyl ester as a reaction raw material tends to contain a small amount of moisture: hydrolysis is used as a side reaction, and competes with a main reaction of alcoholysis, a catalyst MeONa is consumed to generate sodium acetate, and acetic acid is finally generated by exchange of acidic cation resin, and is difficult to remove due to the high boiling point of the acetic acid and is easy to remain in a final sucralose product, so that the product has obvious acidic odor, and the quality of the product is seriously influenced; in addition, due to consumption of MeONa by hydrolysis reaction, MeONa is frequently required to be continuously supplemented in the deacetylation reaction process to ensure complete reaction, which causes large MeONa consumption and load of subsequent procedures such as MeONa removal.
Disclosure of Invention
The invention aims to overcome the defects that sucralose products produced by the prior art have obvious acidic odor, seriously affect the product quality and have large MeONa consumption, and provides a method for preparing sucralose by using sucralose-6-ethyl ester.
In order to achieve the purpose, the technical scheme adopted by the invention is as follows:
a method for preparing sucralose by using sucralose-6-ethyl ester is characterized by comprising the following steps:
1) dissolving sucralose-6-ethyl ester in methanol to form a sucralose-6-ethyl ester solution, wherein the dosage proportion of the sucralose-6-ethyl ester per gram is 3-10 ml of methanol for dissolving;
2) adding alkaline anion resin into the sucralose-6-ethyl ester solution, wherein the dosage proportion is that per gram of sucralose-6-ethyl ester, 0.2-2 grams of alkaline anion resin is used, stirring and reacting at the temperature of 10-60 ℃ to fully convert the sucralose-6-ethyl ester, and the reaction time is 0.5-24 hours;
3) after the reaction is finished, filtering the reaction solution to remove the basic anion resin to obtain a filtrate containing the sucralose crude product, wherein the content of acetic acid is below the detection limit.
On the basis of the technical scheme, the following further technical scheme is provided:
further purifying the obtained sucralose crude product to obtain a sucralose finished product, wherein the finished product has no acidic odor.
The basic anion resin is resin containing amino or quaternary ammonium base as basic groups.
The resin containing amino or quaternary ammonium base as basic group includes gel type and macroporous resin, such as 717 strongly basic type I anion resin (hydroxide type), 719 strongly basic type II anion resin (hydroxide type), Amberlyst®Resin A21, Amberlyst®A26-OH type resin, Amberlite®IRA402-OH type resin, Amberlite®Any of the IRA-900-OH type resins, and other brands of equivalent types of resins.
In the above technical scheme, the inventors found that the preparation of sucralose by catalytic deacetylation with basic anionic resin is very advantageous (as shown in fig. 3): on the basis of high-efficiency and reliable catalytic deacetylation, the alkaline anion resin can be removed and recycled through simple filtration, the extra sodium ion removal step is avoided, the operation steps are reduced, the material consumption and the generated wastewater are reduced, particularly, due to the adsorption effect of the alkaline anion resin, the acetic acid possibly generated in the deacetylation process can be adsorbed, so that no acetic acid residue exists in the final sucralose product, and the product quality is greatly improved.
Compared with the existing deacetylation process of the MeONa/MeOH system, the method has the following advantages:
1. the process of removing sodium ions by using the cationic resin is omitted, so that the material loss and the generation of wastewater are reduced, the clean production is facilitated, and the production cost is comprehensively reduced.
2. The basic anionic resin can be simply removed by filtration and can be recycled.
3. The alkaline anion resin can simultaneously adsorb acetic acid possibly generated in the deacetylation process, and the sour problem caused by residual acetic acid in the product is avoided.
Drawings
FIG. 1 is a reaction formula of a process for synthesizing sucralose by a single-group protection method;
FIG. 2 is a schematic representation of the competition between alcoholysis and hydrolysis reactions in a MeONa/MeOH system;
FIG. 3 is a schematic diagram of the deacetylation reaction catalyzed by basic anion resin (taking quaternary ammonium base type resin as an example).
Detailed Description
Example 1 (comparative example: 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 crude sucralose, and the content of acetic acid in the filtrate is 230 ppm as determined 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%.
Example 2
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 20 g of 717 strongly basic type I anion resin (hydroxyl type) is added into the solution. A mechanical stirring device is arranged on the flask, stirring is started, low-speed stirring is maintained (the rotating speed is not more than 500 revolutions per minute) to ensure that the resin is not broken, after the reaction is maintained at 25 ℃ for 24 hours, the residual of the sucralose-6-ethyl ester is determined to be less than or equal to 0.5 percent (relative peak area) by high performance liquid chromatography, and the 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 was 82%.
Example 3
Adding 100 g of sucralose-6-ethyl ester into a 1000 ml three-neck round-bottom flask, adding 500 ml of methanol, fully dissolving to form a homogeneous solution, and adding 50 g of Amberlyst into the solution®Resin A21. The flask was equipped with a mechanical stirring device, the stirring was started, the stirring was maintained at a low speed (speed not more than 500 rpm) to ensure that the resin did not break, and the temperature was maintained at 60 ℃ for reverse reactionAfter the reaction time of 1 hour, 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 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 91%.
Example 4
Adding 100 g of sucralose-6-ethyl ester into a 1000 ml three-neck round-bottom flask, adding 500 ml of methanol, fully dissolving to form a homogeneous solution, and adding 40 g of Amberlyst into the solution®A26-OH type resin. A mechanical stirring device is arranged on a flask, stirring is started, low-speed stirring is maintained (the rotating speed is not more than 500 revolutions per minute) to ensure that the resin is not broken, after the reaction is maintained at 50 ℃ for 2 hours, 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 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 5
Adding 100 g of sucralose-6-ethyl ester into a 2000 ml three-neck round-bottom flask, adding 1000 ml of methanol, fully dissolving to form a homogeneous solution, and adding 200 g of Amberlite into the solution®IRA-900-OH type resin. A mechanical stirring device is arranged on a flask, stirring is started, low-speed stirring is maintained (the rotating speed is not more than 500 revolutions per minute) to ensure that the resin is not broken, after reaction is maintained at 60 ℃ for 6 hours, 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 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, and further, the sucralose product can be further purified according to a conventional method, and the obtained sucralose finished product has no acidic odor. The yield of sucralose generated by the deacetylation reaction of sucralose-6-ethyl ester determined by high performance liquid chromatography was 93%.
Example 6 (recycled resin for use)
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 Amberlite recovered in example 5 was added to the solution®IRA-900-OH type resin. A mechanical stirring device is arranged on a flask, stirring is started, low-speed stirring is maintained (the rotating speed is not more than 500 revolutions per minute) to ensure that the resin is not broken, after the reaction is maintained at 60 ℃ for 12 hours, 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 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 85%.
The foregoing is merely a preferred embodiment of the invention and is not intended to limit the invention in any manner; those skilled in the art can make numerous possible variations and modifications to the present teachings, or modify equivalent embodiments to equivalent variations, without departing from the scope of the present teachings, using the methods and techniques disclosed above. Therefore, any simple modification, equivalent replacement, equivalent change and modification made to the above embodiments according to the technical essence of the present invention are still within the scope of the protection of the technical solution of the present invention.
Claims (4)
1. A method for preparing sucralose by using sucralose-6-ethyl ester is characterized by comprising the following steps:
1) dissolving sucralose-6-ethyl ester in methanol to form a sucralose-6-ethyl ester solution, wherein the dosage proportion of the sucralose-6-ethyl ester per gram is 3-10 ml of methanol for dissolving;
2) adding alkaline anion resin into the sucralose-6-ethyl ester solution, wherein the dosage proportion is that per gram of sucralose-6-ethyl ester, 0.2-2 grams of alkaline anion resin is used, stirring and reacting at the temperature of 10-60 ℃ to fully convert the sucralose-6-ethyl ester, and the reaction time is 0.5-24 hours;
3) after the reaction is completed, filtering the reaction solution to remove the basic anion resin, and obtaining a filtrate containing the sucralose crude product.
2. The method for preparing sucralose from sucralose-6-ethyl ester according to claim 1, comprising the following steps:
further purifying the obtained sucralose crude product to obtain a sucralose finished product, wherein the finished product has no acidic odor.
3. The method for preparing sucralose from sucralose-6-ethyl ester according to claim 1, wherein:
the basic anion resin is resin containing amino or quaternary ammonium base as basic groups.
4. The method for preparing sucralose by using sucralose-6-ethyl ester according to claim 3, wherein:
the resin containing amino or quaternary ammonium base as basic group is any one of the following varieties: 717 strongly basic type I anion resin, 719 strongly basic type II anion resin, Amberlyst®Resin A21, Amberlyst®A26-OH type resin, Amberlite®IRA402-OH type resin, Amberlite®IRA-900-OH type resin.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202011384911.0A CN112409419A (en) | 2020-12-02 | 2020-12-02 | Method for preparing sucralose by using sucralose-6-ethyl ester |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202011384911.0A CN112409419A (en) | 2020-12-02 | 2020-12-02 | Method for preparing sucralose by using sucralose-6-ethyl ester |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN112409419A true CN112409419A (en) | 2021-02-26 |
Family
ID=74829487
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202011384911.0A Pending CN112409419A (en) | 2020-12-02 | 2020-12-02 | Method for preparing sucralose by using sucralose-6-ethyl ester |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN112409419A (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2024082156A1 (en) * | 2022-10-19 | 2024-04-25 | 安徽金禾实业股份有限公司 | Method for preparing sucralose crude product by using alcohol-water alkaline hydrolysis system |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5449772A (en) * | 1991-05-21 | 1995-09-12 | Tate & Lyle Public Ltd. Co. | Continuous process for the preparation of sucrose 6-esters |
| US20070227897A1 (en) * | 2006-04-03 | 2007-10-04 | Guangzhou Kehong Food Additive Co., Ltd. | Process for the preparation of sucralose |
| CN101263153A (en) * | 2005-08-30 | 2008-09-10 | 法马德医疗保险私人有限公司 | Process for production of chlorinated sucrose based on hydrophobic affinity chromatography |
| CN104530144A (en) * | 2014-12-09 | 2015-04-22 | 厦门蓝湾科技有限公司 | Reactor and method for preparing glucosamine sulfate |
-
2020
- 2020-12-02 CN CN202011384911.0A patent/CN112409419A/en active Pending
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5449772A (en) * | 1991-05-21 | 1995-09-12 | Tate & Lyle Public Ltd. Co. | Continuous process for the preparation of sucrose 6-esters |
| CN101263153A (en) * | 2005-08-30 | 2008-09-10 | 法马德医疗保险私人有限公司 | Process for production of chlorinated sucrose based on hydrophobic affinity chromatography |
| US20070227897A1 (en) * | 2006-04-03 | 2007-10-04 | Guangzhou Kehong Food Additive Co., Ltd. | Process for the preparation of sucralose |
| CN104530144A (en) * | 2014-12-09 | 2015-04-22 | 厦门蓝湾科技有限公司 | Reactor and method for preparing glucosamine sulfate |
Non-Patent Citations (4)
| Title |
|---|
| 上海建筑设计研究院主编: "《给水排水设计手册：材料设备：续册 4》", 30 April 1994, 中国建筑工业出版社 * |
| 康文通 等: "新型甜味剂三氯蔗糖的研究", 《中国调味品》 * |
| 湛英杰: "甜味剂三氯蔗糖合成新工艺的探索和优化", 《中国优秀博硕士学位论文全文数据库(硕士) 工程科技Ⅰ辑》 * |
| 王亚楼编著: "《化学制药工艺学》", 31 October 2008, 化学工业出版社 * |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2024082156A1 (en) * | 2022-10-19 | 2024-04-25 | 安徽金禾实业股份有限公司 | Method for preparing sucralose crude product by using alcohol-water alkaline hydrolysis system |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| RU2503722C2 (en) | Method of converting polysaccharides in molten inorganic salt hydrate | |
| CN101284850B (en) | Purification and crystallization process of sucralose | |
| EP3392234B1 (en) | Method for producing ferulic acid from corn brans in high purity and high yield | |
| CN112409419A (en) | Method for preparing sucralose by using sucralose-6-ethyl ester | |
| US20120264929A1 (en) | Method for producing n-acetyl-d-glucosamine | |
| KR20140136476A (en) | Process for preparing dialkyl carbonate and diol products | |
| KR101105460B1 (en) | Method for preparing sugar alcohols using ruthenium zirconia catalyst | |
| CN109759138B (en) | Bimetallic material immobilized phosphotungstic acid catalyst, preparation method and application in cellulose hydrolysis | |
| CN105132513A (en) | Method for preparing amoxicillin or ampicillin in full-water-phase through mode | |
| KR0145350B1 (en) | Preparation process for polyoxyalkylene polyol | |
| US6525229B2 (en) | Process for separating ethylene glycol | |
| CN112771059A (en) | Preparation method of sucralose, crude product solution and sucralose | |
| CN114890898B (en) | Method for recycling waste polyester based on alcoholysis of two-component catalyst | |
| WO2022141228A1 (en) | Preparation method for sucralose, crude product solution and sucralose | |
| WO2016113221A1 (en) | Process for producing a purified liquid sugar stream | |
| WO2022141227A1 (en) | Preparation method for sucralose, crude product solution, and sucralose | |
| US8383815B2 (en) | Heterogeneous ruthenium metal catalyst for the production of hydrocodone, hydromorphone or a derivative thereof | |
| CN110776419B (en) | Green and clean production process for preparing dibutyl phthalate | |
| JP2023525650A (en) | Method for producing acetylated sodium hyaluronate | |
| CN112495442A (en) | Method for recycling and preparing organic tin catalyst in sucrose-6-ethyl ester production | |
| US7459584B2 (en) | Process for the preparation of lactic acid and glyceric acid | |
| CN112574258A (en) | Method for controlling sucralose acidity | |
| CN114478655B (en) | Preparation method of high-purity gastrodin hemihydrate | |
| CN116217635B (en) | Deacidifying and purifying method for sucrose-6-acetate | |
| CN117820392A (en) | Preparation method of sucralose |
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 | ||
| RJ01 | Rejection of invention patent application after publication | ||
| RJ01 | Rejection of invention patent application after publication |
Application publication date: 20210226 |