CN101941995A - Method for improving preparation yield of trichlorosucrose-6-acetic ester - Google Patents
Method for improving preparation yield of trichlorosucrose-6-acetic ester Download PDFInfo
- Publication number
- CN101941995A CN101941995A CN2009100631366A CN200910063136A CN101941995A CN 101941995 A CN101941995 A CN 101941995A CN 2009100631366 A CN2009100631366 A CN 2009100631366A CN 200910063136 A CN200910063136 A CN 200910063136A CN 101941995 A CN101941995 A CN 101941995A
- Authority
- CN
- China
- Prior art keywords
- acetic ester
- sucralose
- temperature
- ethyl acetate
- improves
- 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
Landscapes
- Saccharide Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
The invention discloses a method for improving the preparation yield of trichlorosucrose-6-acetic ester. The method comprises the following steps of: firstly dropwise adding a first chlorinating agent into a mixed solvent consisting of two solvents, dropwise adding dimethyl formamide(DMF) solution of sucrose-6-acetic ester, slowly raising temperature until refuxing, preserving heat for 2 hours, adding ethyl acetate or dichloroethane hot solution of a second chlorinating agent, after adding, raising the temperature to 110 DEG C to further chloridize the mixture, reducing the temperature of the material to the room temperature, neutralizing the material with an alkaline, filtering, concentrating the filtrate under vacuum to obtain a solid, adding water and raising the temperature to dissolve the solid, extracting the solution with an extracting agent, and removing the extracting agent under vacuum to obtain the trichlorosucrose-6-acetic ester. The method has the advantages of easy control on reaction conditions, good chloridizing selectivity and high yield of the trichlorosucrose-6-acetic ester.
Description
Technical field
The invention belongs to field of medicine and chemical technology, relate in particular to a kind of method of producing sucralose-6-acetic ester.
Background technology
Prepare sucralose-6-acetic ester by cane sugar-6-acetic ester, more patented technology is disclosed both at home and abroad, when cane sugar-6-acetic ester being carried out chlorination with the preparation sucralose-6-acetic ester, comprehensive existing patented technology, can obviously find, because the chlorizating agent that they adopt mainly contains sulfur oxychloride, phosphorus trichloride, phosphorus pentachloride and phosphorus oxychloride, phosgene, superpalite or two (trichloromethyl) carbonic ether or the like, chlorization condition to each chlorizating agent has all been done detailed research, but the chlorination yield of various patented technologies is unsatisfactory.By comprehensive comparison to the whole bag of tricks, we find, during with chlorinations such as sulfur oxychloride, phosphorus trichloride, phosphorus pentachloride and phosphorus oxychloride, the large percentage of many chlorine cane sugar-6-acetic esters such as tetrachloro cane sugar-6-acetic ester, pentachloro-cane sugar-6-acetic ester, and during with chlorinations such as phosgene, superpalite or two (trichloromethyl) carbonic ethers, the large percentage of low chlorine cane sugar-6-acetic esters such as a chlorine cane sugar-6-acetic ester, dichloro cane sugar-6-acetic ester.Practice result shows, inorganic chlorizating agent is easy to make the cane sugar-6-acetic ester chlorination excessive under the pyritous situation, and the organic chloride agent exists chlorination speed slow when low temperature, the halfway phenomenon of chlorination, if the high-temp chlorination time is oversize, there is the problem of carbonization and tarring again.
Summary of the invention
The objective of the invention is to overcome the defective of prior art, adopt two kinds of chlorizating agents to divide one-step chlorination, thereby a kind of method that sucralose-6-acetic ester prepares yield that improves is provided cane sugar-6-acetic ester.
Technical scheme of the present invention is achieved in that
A kind of method that sucralose-6-acetic ester prepares yield that improves is provided, at first first kind of chlorizating agent is added dropwise in the mixed solvent of being made up of DMF and ethyl acetate or ethylene dichloride, and then the DMF solution of dropping cane sugar-6-acetic ester, slowly be warming up to reflux temperature (80 ℃), be incubated after 2 hours, the ethyl acetate or the ethylene dichloride hot solution (80 ℃) that add second kind of chlorizating agent in batches, after adding, progressively steam ethyl acetate or ethylene dichloride, make temperature rise to 110 ℃, to the chlorination that further heats up of the material of removing ethyl acetate or ethylene dichloride, the insulation chlorination was reduced to room temperature after 2 hours, with the alkali neutralization, filter, vacuum concentration is done filtrate again.Add the water rising temperature for dissolving again, with extraction agent extraction, vacuum removal extraction agent then adds after the water rising temperature for dissolving decrease temperature crystalline again, obtain the sucralose-6-acetic ester crude product, crude product water or acetic acid ethyl dissolution, decolouring, recrystallization obtain the sucralose-6-acetic ester crystal of white.
Aforesaid a kind of method that sucralose-6-acetic ester prepares yield that improves is characterized in that: first kind of chlorizating agent is any one in sulfur oxychloride, phosphorus trichloride, phosphorus pentachloride and the phosphorus oxychloride; Second kind of chlorizating agent is any one in superpalite or two (trichloromethyl) carbonic ether.
Aforesaid a kind of method that sucralose-6-acetic ester prepares yield that improves, it is characterized in that: before 80 ℃ of the described reflux temperatures, with quantitative sulfur oxychloride, phosphorus trichloride, phosphorus pentachloride or phosphorus oxychloride cane sugar-6-acetic ester is carried out the chlorination first time, after 80 ℃ of described reflux temperatures, cane sugar-6-acetic ester is carried out the chlorination second time with superpalite or two (trichloromethyl) carbonic ether.
Aforesaid a kind of method that sucralose-6-acetic ester prepares yield that improves is characterized in that: the chlorating temperature range is at 80～110 ℃ for the second time.
Aforesaid a kind of method that sucralose-6-acetic ester prepares yield that improves, it is characterized in that: the gained material is neutralized to PH=6.8～7.0 with alkali after the described chlorination second time.
Aforesaid a kind of method that sucralose-6-acetic ester prepares yield that improves is characterized in that: the alkali of described neutralization usefulness is any one of yellow soda ash, sodium hydroxide, ammoniacal liquor.
Aforesaid a kind of method that sucralose-6-acetic ester prepares yield that improves, it is characterized in that: described extraction agent is chloroform, ethyl acetate, ethylene dichloride or butylacetate.
The present invention has the advantage that reaction conditions is easy to control, the chlorination selectivity is good, the sucralose-6-acetic ester yield is high.
Embodiment
The invention will be further described below in conjunction with embodiment,
A kind of method that sucralose-6-acetic ester prepares yield that improves is provided, at first the mixed solvent of 300ml DMF and 100ml ethyl acetate composition is cooled to-5 ℃, the entire reaction system is in-micro-vacuum state of 10cmHg, drip the 75g sulfur oxychloride then, holding temperature-5～5 ℃, drip off back insulated and stirred 1 hour, the mixing solutions of Dropwise 5 0g cane sugar-6-acetic ester and 150ml DMF again, 0～10 ℃ of holding temperature, after dripping off, insulated and stirred 1 hour, slowly be warming up to reflux temperature (80 ℃) then, be incubated after 2 hours, the hot solution (80 ℃) formed of Dropwise 5 0g two (trichloromethyl) carbonic ether and 100ml ethyl acetate again, 80～85 ℃ of holding temperatures, after adding, progressively steam ethyl acetate, make temperature rise to 110 ℃, be incubated after 2 hours, material is reduced to room temperature, be neutralized to PH=6.8～7.0 with 20% ammoniacal liquor again, filter, water in the vacuum removal filtrate and DMF use 200ml water rising temperature for dissolving material again, reduce to after the room temperature with the ethyl acetate extraction of 1 times of volume 4 times, combining extraction liquid, vacuum removal ethyl acetate again is cooled to 5 ℃ of crystallizations 24 hours after adding 200ml water rising temperature for dissolving leftover materials, filter, obtain lurid sucralose-6-acetic ester crude product 48g, be warming up to 80～85 ℃ of dissolvings, add the 2g activated carbon decolorizing with 100ml water, filter, be cooled to 5 ℃ of crystallizations 24 hours, refilter, get the pure white Sucralose-6-acetate crystal 3 8.2g of content 99%.
Embodiment 2:
The mixed solvent of 300ml DMF and 100ml ethylene dichloride composition is cooled to-5 ℃, the entire reaction system is in-micro-vacuum state of 10cmHg, drip the 70g phosphorus trichloride then, holding temperature-5～5 ℃, drip off back insulated and stirred 1 hour, the mixing solutions of Dropwise 5 0g cane sugar-6-acetic ester and 150ml DMF again, 0～10 ℃ of holding temperature, after dripping off, insulated and stirred 1 hour, slowly be warming up to backflow (80 ℃) then, be incubated after 2 hours, drip the hot solution (80 ℃) that 75g superpalite and 100ml ethylene dichloride are formed again.80～85 ℃ of holding temperatures, after adding, progressively steam ethylene dichloride (can apply mechanically), make temperature rise to 110 ℃, be incubated after 2 hours, material is reduced to room temperature, be neutralized to PH=6.8～7.0 with 30% liquid caustic soda again, filter, water in the vacuum removal filtrate and DMF, use 200ml water rising temperature for dissolving material again, reduce to after the room temperature with the ethyl acetate extraction of 1 times of volume 4 times combining extraction liquid, vacuum removal ethyl acetate again, be cooled to 5 ℃ of crystallizations 24 hours after adding 200ml water rising temperature for dissolving leftover materials, filter, obtain xanchromatic sucralose-6-acetic ester crude product 46g, be warming up to 70～75 ℃ of dissolvings with the 200ml ethyl acetate, add the 3g activated carbon decolorizing, filter, be cooled to 5 ℃ of crystallizations 24 hours, refilter, get the white sucralose-6-acetic ester crystal 3 5.2g of content 98.2%.
Though above shown detailed embodiment of the present invention, apparent, those skilled in the art is under prerequisite of the present invention, can carry out the part modifications and changes; The content that description is above mentioned is the illustration of property as an illustration only, is not as limitation of the present invention; What have a technical characterictic described herein a kind ofly improves the method that sucralose-6-acetic ester prepares yield, all falls into this patent protection domain.
Claims (7)
1. one kind is improved the method that sucralose-6-acetic ester prepares yield, at first first kind of chlorizating agent is added dropwise in the mixed solvent of being made up of DMF and ethyl acetate or ethylene dichloride, and then the DMF solution of dropping cane sugar-6-acetic ester, slowly be warming up to reflux temperature, be incubated after 2 hours, the ethyl acetate or the ethylene dichloride hot solution that add second kind of chlorizating agent in batches, after adding, progressively steam ethyl acetate or ethylene dichloride, make temperature rise to 110 ℃, to the chlorination that further heats up of the material of removing ethyl acetate or ethylene dichloride, after finishing, the insulation chlorination reduces to room temperature, with the alkali neutralization, filter, vacuum concentration is done filtrate again.Add the water rising temperature for dissolving again, with extraction agent extraction, vacuum removal extraction agent then adds after the water rising temperature for dissolving decrease temperature crystalline again, obtain the sucralose-6-acetic ester crude product, crude product water or acetic acid ethyl dissolution, decolouring, recrystallization obtain the sucralose-6-acetic ester crystal of white.
2. a kind of method that sucralose-6-acetic ester prepares yield that improves as claimed in claim 1 is characterized in that: first kind of chlorizating agent is any one in sulfur oxychloride, phosphorus trichloride, phosphorus pentachloride and the phosphorus oxychloride; Second kind of chlorizating agent is any one in superpalite or two (trichloromethyl) carbonic ether.
3. a kind of method that sucralose-6-acetic ester prepares yield that improves as claimed in claim 1 or 2, it is characterized in that: before 80 ℃ of the described reflux temperatures, with quantitative sulfur oxychloride, phosphorus trichloride, phosphorus pentachloride or phosphorus oxychloride cane sugar-6-acetic ester is carried out the chlorination first time, after 80 ℃ of described reflux temperatures, cane sugar-6-acetic ester is carried out the chlorination second time with superpalite or two (trichloromethyl) carbonic ether.
4. a kind of method that sucralose-6-acetic ester prepares yield that improves as claimed in claim 3 is characterized in that: described second time, the chlorating temperature range was at 80～110 ℃.
5. a kind of method that sucralose-6-acetic ester prepares yield that improves as claimed in claim 3, it is characterized in that: the gained material is neutralized to PH=6.8～7.0 with alkali after the described chlorination second time.
6. a kind of method that sucralose-6-acetic ester prepares yield that improves as claimed in claim 5 is characterized in that: the alkali of described neutralization usefulness is any one of yellow soda ash, sodium hydroxide, ammoniacal liquor.
7. a kind of method that sucralose-6-acetic ester prepares yield that improves as claimed in claim 1, it is characterized in that: described extraction agent is chloroform, ethyl acetate, ethylene dichloride or butylacetate.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2009100631366A CN101941995A (en) | 2009-07-10 | 2009-07-10 | Method for improving preparation yield of trichlorosucrose-6-acetic ester |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2009100631366A CN101941995A (en) | 2009-07-10 | 2009-07-10 | Method for improving preparation yield of trichlorosucrose-6-acetic ester |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN101941995A true CN101941995A (en) | 2011-01-12 |
Family
ID=43434222
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN2009100631366A Pending CN101941995A (en) | 2009-07-10 | 2009-07-10 | Method for improving preparation yield of trichlorosucrose-6-acetic ester |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN101941995A (en) |
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103012509A (en) * | 2012-12-13 | 2013-04-03 | 福建科宏生物工程有限公司 | Method of separating and purifying sucrose-6-acetate mother liquor by salt fractionation |
| CN109942642A (en) * | 2018-12-10 | 2019-06-28 | 安徽金禾实业股份有限公司 | A kind of method for carrying out chlorination neutralization with dimethylamine in Sucralose production |
| CN110078189A (en) * | 2019-03-29 | 2019-08-02 | 翁源广业清怡食品科技有限公司 | A kind of neutralization method of chlorination liquid |
| WO2024082154A1 (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 improved hydrolysis system |
-
2009
- 2009-07-10 CN CN2009100631366A patent/CN101941995A/en active Pending
Cited By (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103012509A (en) * | 2012-12-13 | 2013-04-03 | 福建科宏生物工程有限公司 | Method of separating and purifying sucrose-6-acetate mother liquor by salt fractionation |
| CN103012509B (en) * | 2012-12-13 | 2015-04-15 | 福建科宏生物工程有限公司 | Method of separating and purifying sucrose-6-acetate mother liquor by salt fractionation |
| CN109942642A (en) * | 2018-12-10 | 2019-06-28 | 安徽金禾实业股份有限公司 | A kind of method for carrying out chlorination neutralization with dimethylamine in Sucralose production |
| CN110078189A (en) * | 2019-03-29 | 2019-08-02 | 翁源广业清怡食品科技有限公司 | A kind of neutralization method of chlorination liquid |
| CN110078189B (en) * | 2019-03-29 | 2022-03-15 | 翁源广业清怡食品科技有限公司 | Neutralization method of chlorination reaction liquid |
| WO2024082154A1 (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 improved hydrolysis system |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN102321122B (en) | Method for preparing sucralose from sucralose-6-acetate | |
| CN102417526B (en) | Method for preparing sucralose-6-ester by utilizing phase transfer catalyst to catalyze and chloridize | |
| CN101270136B (en) | Process for preparing sucrose trichloride-6-ester | |
| CN106349245B (en) | A kind of phosphoric acid Xi Gelieting impurity and its preparation method and application | |
| CN101941995A (en) | Method for improving preparation yield of trichlorosucrose-6-acetic ester | |
| CN105646385A (en) | Production technology of cycloserine | |
| CN104193614B (en) | The preparation method of ibuprofen crystallization | |
| CN101121736B (en) | Method of preparing sucralose | |
| CN103626699A (en) | Industrial preparation method of 4,7-dichloroquinoline | |
| CN103396406B (en) | Preparation method of candesartan cilexetil | |
| CN101914064B (en) | Method for preparing sulfachlororyridazine sodium | |
| CN103319548B (en) | A kind of method of purification of cane sugar-6-acetic ester | |
| CN103435567A (en) | Valsartan refining method | |
| CN101270124B (en) | Novel method for purifying and preparing high-purity fluorandiol and fluorandiol salt | |
| CN102127081B (en) | Preparation method of adenine | |
| CN104829590A (en) | Trelagliptin purification method | |
| CN103193252A (en) | Method for producing potassium chloride by adopting carnallite hot-melt brine | |
| CN107383062A (en) | The ANCE of Ceftibuten parent nucleus 7 preparation method | |
| CN106316950A (en) | Gliquidone preparation method | |
| CN105367483A (en) | Preparation method of donepezil hydrochloride | |
| CN105131050A (en) | Preparation method of chlorinating agent and method therewith for preparing sucralose | |
| CN102924369A (en) | Method for synthesizing 3,5-dibromo-4-iodopyridine by one step | |
| CN106083564B (en) | A kind of synthesis of 2,6- dimethyl phenoxyacetic acid and purification process | |
| CN102250119B (en) | Method for preparing nafcillin sodium monohydrate by using nafcillin acid | |
| CN105175250B (en) | A kind of new method synthesizing ciprofibrate |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C02 | Deemed withdrawal of patent application after publication (patent law 2001) | ||
| WD01 | Invention patent application deemed withdrawn after publication |
Application publication date: 20110112 |