CN102702276B - Postprocessing method for glycal reaction solution - Google Patents
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- CN102702276B CN102702276B CN201210186510.3A CN201210186510A CN102702276B CN 102702276 B CN102702276 B CN 102702276B CN 201210186510 A CN201210186510 A CN 201210186510A CN 102702276 B CN102702276 B CN 102702276B
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Abstract
The invention relates to the technical field of glycal, in particular to a postprocessing method for a glycal reaction solution. The glycal reaction solution is washed with acid within one hour until the aqueous phase PH is acidic or neutral, then the glycal reaction solution is washed until the aqueous phase PH is neutral or alkaline, organic phases are separated, and the purified glycal is obtained after drying. According to the postprocessing method for the glycal reaction solution disclosed by the invention, time, labor and cost are saved, waste eluent which can not be processed can not be largely produced, the yield and the purity of the obtained glycal are high, and the method can be used for production on a large scale.
Description
Technical field
The present invention relates to glycal technical field, particularly a kind of post-treating method of glycal reaction solution.
Background technology
Saccharide compound is the material that people live and activity in production is indispensable, and simultaneously sugar also plays pivotal player in life entity process, and it is together with nucleic acid, protein and be called three large living matters.In recent years, along with the development of glycobiology and people are to the great attention of Carbohydrate drugs, carbohydrate chemistry enters a fast-developing period, and increasing chemist and computer MSR Information system are put in the research to carbohydrate chemistry both at home and abroad.At present, the use of Carbohydrate drugs and sales volume occupy very large ratio on the pharmaceutical market.According to statistics, the quantity of the current Carbohydrate drugs commercially sold nearly more than 500 is planted.Because Carbohydrate drugs great majority all act on cell surface, and do not enter cell interior, therefore this kind of medicine is for whole cell and then the interference to whole body, and than entering tenuigenin, endonuclear medicine is much smaller.In this regard, Carbohydrate drugs should be the minimum medicine of toxic side effect.In addition, it has the advantage of himself as medicine or raw material, as cheap in raw material, be easy to get, and has natural chirality and structure diversity.Therefore, the application of saccharide compound in medicine obtains to be studied widely, and Carbohydrate drugs also more and more obtains the attention of people.
In pharmaceutical synthesis and organic reaction, glycal, as important intermediate, plays extremely important role always.Glycal is most important a kind of derivative of unsaturated monose, and it is widely used in the synthesis of various oligosaccharides, oligose, carbohydrate, the glucosides of O-or C-, nucleoside compound and biomacromolecule.Its derivative is at Medicines and Health Product, and the application in daily cosmetics is also increasingly extensive, and the demand of glycal also increases year by year, and people are day by day dense to the interest of its preparation method.But due to high by the restriction glycal market price of its synthesis condition, limit its application in every respect, therefore, develop efficient a, cheapness, be applicable to prepare on a large scale the route of glycal there is very high learning value and economic benefit.
About the aftertreatment patent of glycal and document all fewer, be all generally utilize chromatography column purify or directly wash, it is refining that the method that salt is washed carries out process.At Master degree candidate's academic dissertation " syntheses and properties of L-arabglycal " that Jiangxi Normal University's model is vertical; paper the 17 page; gained 3; the thick product of 4-bis--O-ethanoyl-L-arabglycal is separated by silica gel column chromatography; eluent V (sherwood oil): V (acetic acid ethyl ester)=4:1; obtain colourless oil liquid, gas chromatographic analysis content is 98.6%.But this separation method can only be used for a small amount of sample separation, for a large amount of refining will be very loaded down with trivial details, both lost time and energy, also wasted a large amount of eluents.For direct washing, the method that salt is washed not only makes glycal purity decline, and also can greatly reduce product yield.
Summary of the invention
In order to solve the problem that the man-hour existed in above glycal aftertreatment is long, eluting agent is large, yield is low, purity is low, it is a kind of time saving and energy saving to the invention provides, and saves cost and the post-treating method of the glycal reaction solution that the purity of products obtained therefrom and yield can be made to improve.
The present invention is achieved by the following measures:
A post-treating method for glycal reaction solution, used pickling to aqueous phase pH for acid or neutral, then is washed till aqueous phase pH for neutral or alkaline, be separated organic phase, be drying to obtain refining glycal in one hour by glycal reaction solution.
Described post-treating method, in described acid, hydrionic volumetric molar concentration is 1.14mol/L-2.85mol/L, and the temperature of acid is 0-10 DEG C.
Described post-treating method, acid pH is 4-7, and alkaline pH is 7-10.
Described post-treating method, then to be washed till aqueous phase pH be 7-10 is use alkali or water to wash.
Described post-treating method, described glycal is acetylize arabglycal, acetylated glucal, acetylize gala glycal, acetylize rhamnal, acetylize Fructus Hordei Germinatus glycal, acetylize breast glycal or acetylize Fructus Hordei Germinatus three glycal.
Described post-treating method; described glycal is 3,4-bis--O-ethanoyl-L-arabglycal, three-O-ethanoyl-D-glucals, three-O-ethanoyl-D-gala glycals, two-O-ethanoyl-L-rhamnals, six-O-ethanoyl-D-Fructus Hordei Germinatus glycals, six-O-ethanoyl-D-breast glycal or nine-O-ethanoyl-D-Fructus Hordei Germinatus three glycals.
Described post-treating method, described alkali is sodium carbonate.
Described post-treating method, described acid is hydrochloric acid or sulfuric acid.
Described post-treating method, any one below described glycal reaction solution adopts in two kinds of methods obtains:
A, reductive agent to be distributed in organic solvent to obtain mixture a, halogeno-sugar organic solvent dissolution to be obtained mixture b, at reflux mixture b is added in mixture a, to obtain final product;
B, reductive agent is distributed in water, adds pH adjusting agent, add halogeno-sugar, room temperature reaction, to obtain final product.
In method a, reductive agent is zinc powder, and organic solvent is the mixed solvent of butanone and ethyl acetate, and halogeno-sugar is 2,3,4-tri--O-ethanoyl-1-bromo-L-arabinose;
In method b, reductive agent is zinc powder, and halogeno-sugar is four-O-ethanoyl-1-bromo-D-semi-lactosis.
Those skilled in the art knows, glycal is unstable under acidic condition, so the yield in order to improve glycal, acid generally all can not be used to process glycal reaction solution, and technical scheme of the present invention overcomes this technology prejudice exactly, use diluted acid to process glycal reaction solution first under certain condition, not only can not reduce glycal yield, yield can be improved on the contrary, and the purity of the glycal obtained is also very high.
Beneficial effect of the present invention: the post-treating method of glycal reaction solution of the present invention, time saving and energy saving, save cost, can not produce the useless elutriant that cannot process in a large number, the glycal yield obtained is high, purity is high, and can on a large scale for the production of.
Embodiment
In order to further explain the present invention, below in conjunction with specific embodiment, the solution of the present invention is described, but should be appreciated that these describe just understands the present invention to further help, instead of the claim of invention is limited.
embodiment 1: prepare glycal reaction solution under water-less environment
The preparation of glycal reaction solution: the mixed solvent adding butanone and ethyl acetate in 5L flask, butanone and ethyl acetate volume ratio are 1:1, add 1.5mol reductive agent zinc powder, stir, obtain mixture a; Use the mixed solvent of butanone and ethyl acetate to dissolve 1mol 2,3,4-tri--O-ethanoyl-1-bromo-L-arabinose, stir to obtain mixture b; Intensification is heated to mixture a in flask and refluxes, and reflux temperature is 80 degree, divides 10 batches to add mixture b at reflux wherein, obtains product 3,4-bis--O-ethanoyl-L-arabglycal reaction solution.
The aftertreatment of glycal reaction solution: after filtering reacting liquid, with hydrogen ion concentration be 1.14mol/L, temperature is that glycal reaction solution is washed till aqueous phase pH is 6 for the dilute hydrochloric acid solution of 2 DEG C, the treatment time is 10min; Phase-splitting, it is 7 that organic phase is washed till aqueous phase pH with the sodium carbonate solution that massfraction is 8% again; Phase-splitting, organic phase, after super-dry is concentrated, obtains product 0.923mol, and detecting purity is 95.6%.
comparative example 1
The preparation of glycal reaction solution is identical with embodiment 1, the method that the aftertreatment of glycal reaction solution adopts chromatography column to purify, and the treatment time is 24 hours, more consuming time than embodiment more than 1 22 little time, obtain useless elutriant 50L, obtain product 0.82mol, purity is 96.7%.
In embodiment 1, the yield of product is higher than comparative example 1, illustrates compared with the method that the post-treating method of glycal reaction solution of the present invention and chromatography column are purified, can carry high product yield, and product purity also can reach a higher level.
embodiment 2: prepare glycal reaction solution under water environment
The preparation of glycal reaction solution: add 4L water in 10L flask; add 8mol sodium bicarbonate white powder to dissolve; then 10mol zinc powder is added; 72g cupric sulfate pentahydrate dissolution of solid; add 1mol tetra--O-ethanoyl-1-bromo-D-semi-lactosi; room temperature reaction 24 hours, obtains product three-O-ethanoyl-D-gala glycal reaction solution.
The aftertreatment of glycal reaction solution: after filtering reacting liquid, with the dilution heat of sulfuric acid that the temperature that hydrogen ion concentration is 2.85mol/L is 10 DEG C, reaction solution being washed till aqueous phase pH is 5, and the treatment time is 20min; Phase-splitting, it is 12 that organic phase is washed till aqueous phase pH with the sodium carbonate solution that massfraction is 20% again; Phase-splitting, it is 7 that organic phase washes with water to aqueous phase pH again, and separating obtained organic phase is carried out drying and concentrated, and obtain product 0.64mol, purity is 94.2%.
Comparative example 2
The preparation of glycal reaction solution is identical with embodiment 2, and the aftertreatment of glycal reaction solution adopts the method for chromatography column purification, and the treatment time is 28 hours, more consuming time than embodiment more than 2 26 little time, obtain useless elutriant how many 45L, obtain product 0.42mol, purity is 96.7%.
Comparative example 3
The preparation of glycal reaction solution is identical with embodiment 2, is 2.85mol/L by hydrogen ion concentration, and temperature is the dilute sulphuric acid processing reaction liquid of 20 DEG C, and other post-processing steps are identical with embodiment 2, obtain product 0.51mol, and purity is 63.7%.
In embodiment 2, the yield of product is than comparative example 2 and comparative example 3 height, and illustrate compared with the method that the post-treating method of glycal reaction solution of the present invention and chromatography column are purified, can carry high product yield, product purity also can reach a higher level.
embodiment 3
In 5L flask, add methylene dichloride, add 1.5mol reductive agent zinc powder, stir, obtain mixture a; Use methylene dichloride to dissolve 1mol tetra--O-ethanoyl-1-bromo-D-Glucose, stir to obtain mixture b; Intensification is heated to mixture a in flask and refluxes, and reflux temperature is 40 degree, divides 10 batches to add mixture b at reflux wherein, obtains product three-O-ethanoyl-D-glucal reaction solution.
The aftertreatment of glycal reaction solution: after filtering reacting liquid, with hydrogen ion concentration be 2mol/L, temperature is that glycal reaction solution is washed till aqueous phase pH is 6.5 for the dilute hydrochloric acid solution of 5 DEG C, the treatment time is 10min; Phase-splitting, organic phase wash with water again to aqueous phase pH be 7.2; Phase-splitting, organic phase, after super-dry is concentrated, obtains product 0.935mol, and detecting purity is 94.6%.
embodiment 4
In 5L flask, add ethyl acetate, add 1.5mol reductive agent zinc powder, then add 0.32mol ammonium chloride, stir, obtain mixture a; Use acetic acid ethyl dissolution 1mol tri--O-ethanoyl-1-bromo-L-rhamnosyl, stir to obtain mixture b; Intensification is heated to mixture a in flask and refluxes, and reflux temperature is 80 degree, divides 10 batches to add mixture b at reflux wherein, obtains product two-O-ethanoyl-L-rhamnal reaction solution.
The aftertreatment of glycal reaction solution: after filtering reacting liquid, with hydrogen ion concentration be 2.2mol/L, temperature is that glycal reaction solution is washed till aqueous phase pH is 5 for the dilute hydrochloric acid solution of 7 DEG C, the treatment time is 5min; Phase-splitting, it is 7.2 that organic phase is washed till aqueous phase pH with 8% sodium carbonate solution again; Phase-splitting, organic phase, after super-dry is concentrated, obtains product 0.915mol, and detecting purity is 92.6%.
Claims (2)
1. a post-treating method for glycal reaction solution, is characterized in that
The preparation of glycal reaction solution: the mixed solvent adding butanone and ethyl acetate in 5L flask, butanone and ethyl acetate volume ratio are 1:1, add 1.5mol reductive agent zinc powder, stir, obtain mixture a; Use the mixed solvent of butanone and ethyl acetate to dissolve 1mol 2,3,4-tri--O-ethanoyl-1-bromo-L-arabinose, stir to obtain mixture b; Intensification is heated to mixture a in flask and refluxes, and reflux temperature is 80 degree, divides 10 batches to add mixture b at reflux wherein, obtains product 3,4-bis--O-ethanoyl-L-arabglycal reaction solution;
The aftertreatment of glycal reaction solution: after filtering reacting liquid, with hydrogen ion concentration be 1.14mol/L, temperature is that glycal reaction solution is washed till aqueous phase pH is 6 for the dilute hydrochloric acid solution of 2 DEG C, the treatment time is 10min; Phase-splitting, it is 7 that organic phase is washed till aqueous phase pH with the sodium carbonate solution that massfraction is 8% again; Phase-splitting, organic phase, after super-dry is concentrated, obtains product 0.923mol, and detecting purity is 95.6%.
2. a post-treating method for glycal reaction solution, is characterized in that
The preparation of glycal reaction solution: add 4L water in 10L flask, add 8mol sodium bicarbonate white powder to dissolve, then 10mol zinc powder is added, 72g cupric sulfate pentahydrate dissolution of solid, add 1mol tetra--O-ethanoyl-1-bromo-D-semi-lactosi, room temperature reaction 24 hours, obtains product three-O-ethanoyl-D-gala glycal reaction solution;
The aftertreatment of glycal reaction solution: after filtering reacting liquid, with the dilution heat of sulfuric acid that the temperature that hydrogen ion concentration is 2.85mol/L is 10 DEG C, reaction solution being washed till aqueous phase pH is 5, and the treatment time is 20min; Phase-splitting, it is 12 that organic phase is washed till aqueous phase pH with the sodium carbonate solution that massfraction is 20% again; Phase-splitting, it is 7 that organic phase washes with water to aqueous phase pH again, and separating obtained organic phase is carried out drying and concentrated, and obtain product 0.64mol, purity is 94.2%.
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| CN103694208B (en) * | 2013-12-23 | 2015-08-05 | 江西苏克尔新材料有限公司 | The preparation method of acetylize L-arabinose alkene |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2008069440A1 (en) * | 2006-12-06 | 2008-06-12 | Samchully Pharm. Co., Ltd. | The preparation method of 2-de0xy-l-rib0se |
| CN101245057A (en) * | 2007-02-13 | 2008-08-20 | 中国科学院成都生物研究所 | Process for producing glucal |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2008069440A1 (en) * | 2006-12-06 | 2008-06-12 | Samchully Pharm. Co., Ltd. | The preparation method of 2-de0xy-l-rib0se |
| CN101245057A (en) * | 2007-02-13 | 2008-08-20 | 中国科学院成都生物研究所 | Process for producing glucal |
Non-Patent Citations (1)
| Title |
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| 2-脱氧-D-葡萄糖的合成;徐淑周 等;《应用化工》;20100630;第39卷(第6期);946-948 * |
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