CN100586941C - Separation purification method from the vitamins C process for producing 3-O-alkyl ascorbic acid aether by one-step - Google Patents
Separation purification method from the vitamins C process for producing 3-O-alkyl ascorbic acid aether by one-step Download PDFInfo
- Publication number
- CN100586941C CN100586941C CN200710130927A CN200710130927A CN100586941C CN 100586941 C CN100586941 C CN 100586941C CN 200710130927 A CN200710130927 A CN 200710130927A CN 200710130927 A CN200710130927 A CN 200710130927A CN 100586941 C CN100586941 C CN 100586941C
- Authority
- CN
- China
- Prior art keywords
- ascorbic acid
- alkyl ascorbic
- vitamins
- acid ether
- effluent liquid
- 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.)
- Active
Links
Landscapes
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Treatment Of Liquids With Adsorbents In General (AREA)
Abstract
The invention discloses from the separation purification method of vitamins C process for producing 3-O-alkyl ascorbic acid aether by one-step.This method comprises the steps: that vitamins C, alkali, alkylating reagent react in solvent, synthetic 3-O-alkyl ascorbic acid ether; Reaction finishes, and reclaims reaction solvent, the resistates thin up, and last strongly basic anion exchange resin post carries out ion-exchange, and washing is to effluent liquid pH≤8; Use the Diluted Acid Washing post again, the effluent liquid that will contain 3-O-alkyl ascorbic acid ether combines, and can not stop wash-out when having 3-O-alkyl ascorbic acid ether in the last effluent liquid; Wash-out carries out concentrating under reduced pressure and crystallization with elutriant after finishing, and obtains the 3-O-alkyl ascorbic acid ether of purifying.The present invention has adopted the separation method of ion-exchange, avoids using a large amount of inflammable and explosive organic solvents, and is safe, and the purification good separating effect is saved cost.
Description
Technical field
The present invention a kind ofly prepares the separation purification method of 3-O-alkyl ascorbic acid ether from the vitamins C one-step synthesis, is specifically related to adopt methods such as ion-exchange that 3-O-alkyl ascorbic acid ether and impurity are carried out separation processes.
Background technology
3-O-alkyl ascorbic acid ether is a kind of very useful vitamin C derivatives, it is not only highly stable on chemical property, is non-discoloring vitamin C derivatives, and is the hydrophilic amphiprotic substance of oleophylic, this has expanded its range of application widely, especially the application in detergents and cosmetic.3-O-alkyl ascorbic acid ether is easy to see through stratum corneum and enters corium, brings into play ascorbic biological effectiveness thereby it enters to be very easy to behind the body be decomposed by intravital biological enzyme.The preparation of 3-O-alkyl ascorbic acid ether at present all is the method by chemosynthesis, and a kind of is three-step synthesis method; Another kind is an one-step synthesis.
One-step synthesis technology is simple, and facility investment is little, and European patent EP 086554 and Japanese Patent JP2005320310 all report to some extent to single stage method.But the one-step synthesis reaction product is complicated, in order to obtain purified product, often purifies by silica gel column chromatography, consumes a large amount of solvents, is not suitable for large-scale commercial production.
Summary of the invention
The object of the present invention is to provide a kind of more cost effective separation purifying technique, remove from and use inflammable and explosive organic solvent, operational safety, the separation efficiency height, cost is low.
The objective of the invention is to realize by following measures:
A kind ofly prepare the separation purification method of 3-O-alkyl ascorbic acid ether from the vitamins C one-step synthesis, this method comprises the steps:
A, vitamins C, alkali, alkylating reagent react in solvent, synthetic 3-O-alkyl ascorbic acid ether; [among the EP086554 vitamins C, alkali, alkylating reagent, solvent are added in the reactor, stir and react 0～80 ℃ of temperature of reaction, vitamins C: alkali: alkylating reagent=1: 1: 1 (mol).Earlier vitamins C, alkali, solvent are added stirring and dissolving in the reactor among the JP2005320310, add the alkylating reagent back flow reaction then, vitamins C: alkali: alkylating reagent=1: 1.1: 1.1 (mol)].
B, reaction finish, and reclaim reaction solvent (can take the mode of underpressure distillation), the resistates thin up, and last strongly basic anion exchange resin post carries out ion-exchange, washing, to effluent liquid PH≤8; Use the Diluted Acid Washing post then, the effluent liquid that will contain 3-O-alkyl ascorbic acid ether combines, and can not stop wash-out when having 3-O-alkyl ascorbic acid ether in the last effluent liquid;
After c, wash-out finish, the effluent liquid that merges is carried out concentrating under reduced pressure and crystallization, obtain the 3-O-alkyl ascorbic acid ether of purifying.
In above-mentioned processing method, used alkali is any in sodium bicarbonate, yellow soda ash, salt of wormwood, sodium methylate or the triethylamine; Used alkylating reagent is any in bromo alkane, alkane iodide, methylsulfonyl alkane or the benzenesulfonyl alkane, and the alkane carbon number is 1～8; Used solvent is any or multiple in methyl alcohol, ethanol, Virahol, tetrahydrofuran (THF), dimethyl sulfoxide (DMSO), dimethyl formamide or the acetone; Used strongly basic anion exchange resin is highly basic acrylic acid type anion exchange resin (as 213,703) or highly basic styrene series anion exchange resin (as 717, D201, D290, D231, AmberlystA26 or Amberlite FPA97).Used diluted acid is that concentration is 0.1～1% organic acid, as formic acid, and acetate, propionic acid etc.Ion exchange process in the method can adopt step ion exchange column, also can adopt continuous ion exchange apparatus.
Beneficial effect: the present invention provides and a kind ofly prepares the separation purification method of 3-O-alkyl ascorbic acid ether from the vitamins C one-step synthesis, and is simple for process, safe, consumes lowly, pollutes few.
Because the present invention has adopted the separation method of ion-exchange, can with the vitamins C and the 3-O-alkyl ascorbic acid ether of resins exchange, separate with the impurity that does not exchange, use the weak acid wash-out again, vitamins C can not wash-out, and 3-O-alkyl ascorbic acid ether is eluted, and has therefore reached the isolating effect of purifying.By adopting this technology, can avoid using a large amount of inflammable and explosive organic solvents, security is higher, has saved production cost.
Embodiment
Below in conjunction with embodiment the present invention is further described in detail.
Embodiment 1:
1.76 the gram vitamins C, 15ml methyl alcohol, 1.2 gram triethylamines stir and make dissolving fully, add 1.3 gram methanesulfonic methyl esters, back flow reaction 2 hours, synthetic 3-O-alkyl ascorbic acid ether.Remove solvent under reduced pressure, residue adds water 4ml dissolving, gets the reaction product aqueous solution, and is standby.
Prepare the glass column that 50ml resin anion(R.A) 717 is housed, resin carries out pre-treatment: with the sodium hydroxide 200ml of the hydrochloric acid of the sodium hydroxide 200ml of 1N, distillation washing 200ml, 1N or sulfuric acid 200ml, distillation washing 200ml, the 1N washing of regenerating, be washed till neutrality with distilled water at last successively.
With above-mentioned reaction product aqueous solution upper prop, wash post with water, until effluent liquid PH≤8.Use 1% aqueous acetic acid instead and wash post, collect effluent liquid, with thin-layer chromatography or liquid chromatographic detection, every collection 10ml detects once, the effluent liquid that will contain product combines, and can not stop wash-out when having product 3-O-methyl xitix in the last effluent liquid.The effluent liquid that will contain product is evaporated to dried, uses the ethyl acetate crystallization, obtains product 3-O-methyl xitix 0.90 gram, liquid chromatographic detection, and with the standard specimen contrast, purity is 98%, yield 47%.
Embodiment 2:
1.76 the gram vitamins C, 15ml dimethyl sulfoxide (DMSO), 0.54 gram sodium methylate, 1.44 gram methyl iodide, stirring at room reaction 24 hours, synthetic 3-O-alkyl ascorbic acid ether.Remove solvent under reduced pressure, residue adds water 4ml dissolving, gets the reaction product aqueous solution, and is standby.
Prepare the glass column that 50ml resin anion(R.A) D201 is housed, resin carries out pre-treatment: with the sodium hydroxide 200ml of the hydrochloric acid of the sodium hydroxide 200ml of 1N, distillation washing 200ml, 1N or sulfuric acid 200ml, distillation washing 200ml, the 1N washing of regenerating, be washed till neutrality with distilled water at last successively.
With above-mentioned reaction product aqueous solution upper prop, wash post with water, until effluent liquid PH≤8.Use 0.5% aqueous formic acid instead and wash post, collect effluent liquid, with thin-layer chromatography or liquid chromatographic detection, every collection 10ml detects once, the effluent liquid that will contain product (3-O-alkyl ascorbic acid ether) combines, and can not stop wash-out when having product 3-O-methyl xitix in the last effluent liquid.
The effluent liquid that will contain product is evaporated to dried, and crystallization is separated out in the resistates cooling.Use re-crystallizing in ethyl acetate, obtain 3-O-methyl xitix 0.92 gram, liquid chromatographic detection, with the standard specimen contrast, purity is 98.5%, yield 48%.
Embodiment 3:
1.76 the gram vitamins C, 15ml tetrahydrofuran (THF)-dimethyl sulfoxide (DMSO) (1: 1 v/v), 1.38 gram salt of wormwood stir and make dissolving fully, add 1.84 gram butyl bromides, stirring at room reaction 24 hours, synthetic 3-O-alkyl ascorbic acid ether.Remove solvent under reduced pressure, residue adds water 5ml dissolving, gets the reaction product aqueous solution, and is standby.
Prepare a glass column that 50ml resin anion(R.A) Amberlite FPA97 is housed, resin carries out pre-treatment: with the sodium hydroxide 200ml of the hydrochloric acid of the sodium hydroxide 200ml of 1N, distillation washing 200ml, 1N or sulfuric acid 200ml, distillation washing 200ml, the 1N washing of regenerating, be washed till neutrality with distilled water at last successively.
With above-mentioned reaction product aqueous solution upper prop, wash post with water, until effluent liquid PH≤8.Use 0.3% the propionic acid aqueous solution instead and wash post, collect effluent liquid, with thin-layer chromatography or liquid chromatographic detection, every collection 20ml detects once, the effluent liquid that will contain product (3-O-alkyl ascorbic acid ether) combines, and can not stop wash-out when having product 3-O-butyl xitix in the last effluent liquid.
The effluent liquid that will contain product is evaporated to dried, uses the ethyl acetate crystallization, obtains product 3-O-butyl xitix 0.70 gram, liquid chromatographic detection, and with the standard specimen contrast, purity is 98.5%, yield 30%.
Claims (6)
1, a kind ofly prepares the separation purification method of 3-O-alkyl ascorbic acid ether, it is characterized in that this method comprises the steps: from the vitamins C one-step synthesis
A, vitamins C, alkali, alkylating reagent react in solvent, synthetic 3-O-alkyl ascorbic acid ether;
B, reaction finish, and reclaim reaction solvent, the resistates thin up, and last strongly basic anion exchange resin post carries out ion-exchange, and washing is to effluent liquid PH≤8; Use the Diluted Acid Washing post then, the effluent liquid that will contain 3-O-alkyl ascorbic acid ether combines, and can not stop wash-out when having 3-O-alkyl ascorbic acid ether in the last effluent liquid;
After c, wash-out finish, the effluent liquid that merges is carried out concentrating under reduced pressure and crystallization, obtain the 3-O-alkyl ascorbic acid ether of purifying.
2, according to claim 1ly prepare the separation purification method of 3-O-alkyl ascorbic acid ether, it is characterized in that used alkali is any in sodium bicarbonate, yellow soda ash, salt of wormwood, sodium methylate or the triethylamine from the vitamins C one-step synthesis; Used alkylating reagent is any in bromo alkane, alkane iodide, methylsulfonyl alkane or the benzenesulfonyl alkane, and the alkane carbon number is 1～8; Used solvent is any or multiple in methyl alcohol, ethanol, Virahol, tetrahydrofuran (THF), dimethyl sulfoxide (DMSO), dimethyl formamide or the acetone.
3, according to claim 1ly prepare the separation purification method of 3-O-alkyl ascorbic acid ether, it is characterized in that used strongly basic anion exchange resin is highly basic acrylic acid type anion exchange resin or highly basic styrene series anion exchange resin from the vitamins C one-step synthesis; Used diluted acid is that concentration is 0.1～1% organic acid.
4, the separation purification method for preparing 3-O-alkyl ascorbic acid ether from the vitamins C one-step synthesis according to claim 3, it is characterized in that the highly basic acrylic acid type anion exchange resin is 213,703, the highly basic styrene series anion exchange resin is 717, D201, D290, D231, AmberlystA26 or Amberlite FPA97.
5, according to claim 3ly prepare the separation purification method of 3-O-alkyl ascorbic acid ether, it is characterized in that organic acid is formic acid, acetate or propionic acid from the vitamins C one-step synthesis.
6, according to claim 3ly prepare the separation purification method of 3-O-alkyl ascorbic acid ether, it is characterized in that ion-exchange adopts step ion exchange column or adopt continuous ion exchange apparatus from the vitamins C one-step synthesis.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN200710130927A CN100586941C (en) | 2007-08-22 | 2007-08-22 | Separation purification method from the vitamins C process for producing 3-O-alkyl ascorbic acid aether by one-step |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN200710130927A CN100586941C (en) | 2007-08-22 | 2007-08-22 | Separation purification method from the vitamins C process for producing 3-O-alkyl ascorbic acid aether by one-step |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN101130534A CN101130534A (en) | 2008-02-27 |
| CN100586941C true CN100586941C (en) | 2010-02-03 |
Family
ID=39127960
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN200710130927A Active CN100586941C (en) | 2007-08-22 | 2007-08-22 | Separation purification method from the vitamins C process for producing 3-O-alkyl ascorbic acid aether by one-step |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN100586941C (en) |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN116410346A (en) * | 2021-12-31 | 2023-07-11 | 华熙生物科技股份有限公司 | Reductive hyaluronic acid ester and preparation method thereof |
-
2007
- 2007-08-22 CN CN200710130927A patent/CN100586941C/en active Active
Also Published As
| Publication number | Publication date |
|---|---|
| CN101130534A (en) | 2008-02-27 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN107501045B (en) | Method for separating and purifying butanetriol from fermentation liquor by using macroporous adsorption resin | |
| CN102627675A (en) | Method for preparing cane sugar-6-ester | |
| CN1453284A (en) | Synthesis of trichlorosucrose | |
| CN103864859B (en) | A kind of preparation method of Sucralose | |
| CN104557845A (en) | Method for preparing lubiprostone compound | |
| CN114605366A (en) | Synthesis method and synthesis system for continuous flow preparation of hydroxypropyl pyranotriol | |
| CN100586941C (en) | Separation purification method from the vitamins C process for producing 3-O-alkyl ascorbic acid aether by one-step | |
| CN102070635B (en) | Preparation method for ganciclovir valine ester derivative | |
| CN102603603B (en) | Method for preparing (S)-oxiracetam | |
| CN104418825B (en) | The method of purification of Lipstatin | |
| CN104961787B (en) | Synthetic method of cordycepin | |
| CN110734443B (en) | Preparation method of tadalafil-related substance I | |
| CN106316935B (en) | A kind of preparation method of Abemaciclib intermediate | |
| CN102203047B (en) | Process for production of optically active organic carboxylic acid | |
| CN114478658A (en) | Synthesis method of monatibavir | |
| CN112142697A (en) | Vc ethyl ether production process | |
| CN102286000A (en) | Preparation method of cefonicid and medicinal salts thereof | |
| CN110003180A (en) | Pyrroles-pyridine-pyrrole class compound post-processing purification process | |
| CN110894198A (en) | Xanthine compound and preparation method and application thereof | |
| CN102603605B (en) | Preparation method of (S)-4-hydroxy-2-oxo-1-pyrrolidineacetamide | |
| CN109305991A (en) | A kind of P1,P4The preparation method of-two (uridine 5 ' -) Magcophos | |
| CN102603604B (en) | Preparation method of (S)-4-hydroxy-2-oxo-1-pyrrolidine acetamide | |
| CN112209809B (en) | Method for decoloring butanetriol fermentation liquor by using anion exchange resin | |
| CN114085130B (en) | Method for synthesizing ((1R,8S,9S, Z) -bicyclo [6.1.0] non-4-en-9-yl) methanol | |
| CN102796145B (en) | Preparation method of sucrose-6-benzoate |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C14 | Grant of patent or utility model | ||
| GR01 | Patent grant |