CN102757367A - Splitting process of racemic ethyl benzene sulfonic acid - Google Patents
Splitting process of racemic ethyl benzene sulfonic acid Download PDFInfo
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- CN102757367A CN102757367A CN2012102519023A CN201210251902A CN102757367A CN 102757367 A CN102757367 A CN 102757367A CN 2012102519023 A CN2012102519023 A CN 2012102519023A CN 201210251902 A CN201210251902 A CN 201210251902A CN 102757367 A CN102757367 A CN 102757367A
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- sulfonic acid
- ethyl sulfonic
- aqueous solution
- benzene sulfonic
- benzene ethyl
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Abstract
The invention relates to a splitting process of racemic ethyl benzene sulfonic acid. As to the problems that a common resolving agent for splitting the ethyl benzene sulfonic acid is an alkaline splitting agent with optical activity, very high in price and not easy to get, the splitting process of the racemic ethyl benzene sulfonic acid is characterized by comprising the steps of: dissolving 1mol of L-p-hydroxyphenylglycine glycine and 1mol of concentrated sulfuric acid into 20mol of water, adding aqueous solution containing racemic ethyl benzene sulfonic acid under a reflux state, keeping refluxing for 1 hour, then cooling to 20 DEG G, separating, washing and drying the complex salt of L-p-hydroxyphenylglycine glycine and D-ethyl benzene sulfonic acid, and neutralizing the complex salt by inorganic base aqueous solution until the PH is 4-8; devitrifying, separating and repeatedly removing salt of the mother liquor by methanol, evaporating to obtain the D-ethyl benzene sulfonic acid, and carrying out racemization applying on the mother liquor under an alkaline condition. According to the invention, the material is convenient to take; and the splitting process is simple, and the splitting efficiency is high.
Description
Technical field
The present invention relates to a kind of resolution process of DL benzene ethyl sulfonic acid.
Background technology
In the production process of left-handed D-pHPG; Therefore the dextrorotation benzene ethyl sulfonic acid that needs single opticity must need resolving agent that DL benzene ethyl sulfonic acid is split, and resolving agent commonly used is the alkaline resolving agent with opticity; Price is all very expensive, and is not easy to obtain.
Summary of the invention
The present invention is directed to the defective that prior art exists, a kind of resolution process of DL benzene ethyl sulfonic acid is provided, the resolution process flow process is simple, and transformation efficiency is high, and cost is lower.
For this reason, the present invention takes following technical scheme: a kind of resolution process of DL benzene ethyl sulfonic acid is characterized in that the left-handed D-pHPG of 1mol and the 1mol vitriol oil are dissolved in the 20mol water; Reflux state adds down the aqueous solution that contains DL benzene ethyl sulfonic acid, adds to keep backflow 1h, reduces temperature to 20 ℃ subsequently; Separate, the dry double salt that obtains left-handed D-pHPG and the formation of dextrorotation benzene ethyl sulfonic acid of washing, above-mentioned double salt is neutralized to PH between 4-8 with inorganic base aqueous solution; Crystallization separates, and mother liquor is with methyl alcohol desalination repeatedly; Evaporate to dryness gets dextrorotation benzene ethyl sulfonic acid, and mother liquor racemization under alkaline condition is applied mechanically.The equation of reaction is following:
Described inorganic base aqueous solution comprises aqueous sodium hydroxide solution, ammoniacal liquor, potassium hydroxide aqueous solution.
Described inorganic base aqueous solution is preferably aqueous sodium hydroxide solution, and pH value is neutralized to 7.
The present invention adopts midbody left-handed D-pHPG in amoxycilline Trihydrate bp commonly used as resolving agent; Utilize this resolving agent to split DL benzene ethyl sulfonic acid; The double salt that left-handed D-pHPG that fractionation obtains and dextrorotation benzene ethyl sulfonic acid form is water-soluble little, is difficult for racemization under the high temperature catalyst-free condition.Utilize inorganic base aqueous solution hydrolysis, crystallization again, separate, desalination obtains the mixed solution of left-handed D-pHPG and dextrorotation benzene ethyl sulfonic acid repeatedly; Its phase purity is 98%; Total recovery is 40%, 21 ° of optically-actives (20 ℃); Raw material of the present invention is taken conveniently, and the resolution process flow process is simple, fractionation efficient is high.
Embodiment
Below in conjunction with embodiment the present invention is further described, but protection scope of the present invention is not limited to the expression scope of embodiment.
A kind of reaction equation of resolution process of DL benzene ethyl sulfonic acid is following:
(±)-PES is a DL benzene ethyl sulfonic acid in the following formula, and (-)-HPG-(+)-PES Salt is the double salt that left-handed D-pHPG and dextrorotation benzene ethyl sulfonic acid form, and (-)-HPG is the left-handed D-pHPG of target product, and (+)-PES is a dextrorotation benzene ethyl sulfonic acid.
2) technology:
The left-handed D-pHPG of 1mol and the 1mol vitriol oil are dissolved in the 20mol water, and reflux state adds the aqueous solution that contains 1mol DL benzene ethyl sulfonic acid down, add to keep backflow 1h; Reduce the temperature to 20 ℃ subsequently, separate, the dry double salt that obtains left-handed D-pHPG and the formation of dextrorotation benzene ethyl sulfonic acid of washing; Double salt is neutralized to PH (preferred 7) between 4-8 with inorganic base aqueous solution (including but not limited to aqueous sodium hydroxide solution, ammoniacal liquor, potassium hydroxide aqueous solution etc., preferred aqueous sodium hydroxide solution); Crystallization separates, and mother liquor is with methyl alcohol desalination repeatedly; Evaporate to dryness gets dextrorotation benzene ethyl sulfonic acid, and liquid phase purity is 98%, and total recovery is 40%; 21 ° of optically-actives (20 ℃, dissolve with methanol), racemization is applied mechanically under the mother liquor alkaline condition.
The present invention adopts midbody left-handed D-pHPG in amoxycilline Trihydrate bp commonly used as resolving agent; Utilize this resolving agent to split DL benzene ethyl sulfonic acid; The double salt that left-handed D-pHPG that fractionation obtains and dextrorotation benzene ethyl sulfonic acid form is water-soluble little, is difficult for racemization under the high temperature catalyst-free condition.Utilize inorganic base aqueous solution hydrolysis, crystallization again, separate, desalination obtains the mixed solution of left-handed D-pHPG and dextrorotation benzene ethyl sulfonic acid repeatedly, and raw material of the present invention is taken conveniently, and the resolution process flow process is simple, fractionation efficient is high.
Claims (3)
1. the resolution process of a DL benzene ethyl sulfonic acid is characterized in that the left-handed D-pHPG of 1mol and the 1mol vitriol oil are dissolved in the 20mol water, and reflux state adds the aqueous solution that contains DL benzene ethyl sulfonic acid down; Add and keep backflow 1h, reduce temperature to 20 ℃ subsequently, separate; The dry double salt that obtains left-handed D-pHPG and the formation of dextrorotation benzene ethyl sulfonic acid of washing, above-mentioned double salt is neutralized to PH between 4-8 with inorganic base aqueous solution, crystallization; Separate; Mother liquor is with methyl alcohol desalination repeatedly, and evaporate to dryness gets dextrorotation benzene ethyl sulfonic acid, and mother liquor racemization under alkaline condition is applied mechanically.
2. the resolution process of a kind of DL benzene ethyl sulfonic acid according to claim 1 is characterized in that described inorganic base aqueous solution comprises aqueous sodium hydroxide solution, ammoniacal liquor, potassium hydroxide aqueous solution.
3. the resolution process of a kind of DL benzene ethyl sulfonic acid according to claim 1 is characterized in that described inorganic base aqueous solution is preferably aqueous sodium hydroxide solution, and pH value is neutralized to 7.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
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| CN2012102519023A CN102757367A (en) | 2012-07-20 | 2012-07-20 | Splitting process of racemic ethyl benzene sulfonic acid |
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| CN2012102519023A CN102757367A (en) | 2012-07-20 | 2012-07-20 | Splitting process of racemic ethyl benzene sulfonic acid |
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| CN102757367A true CN102757367A (en) | 2012-10-31 |
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| CN2012102519023A Pending CN102757367A (en) | 2012-07-20 | 2012-07-20 | Splitting process of racemic ethyl benzene sulfonic acid |
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Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103787929A (en) * | 2014-03-03 | 2014-05-14 | 济南盛弘医药科技有限公司 | D,L-sulfophenylacetic acid resolution method |
| CN110467537A (en) * | 2019-08-08 | 2019-11-19 | 河南新天地药业股份有限公司 | A kind of preparation process of D-HPG |
| CN115850127A (en) * | 2022-11-28 | 2023-03-28 | 湖北省宏源药业科技股份有限公司 | Synthesis method of L-p-hydroxyphenylglycine phenyl ethanesulfonate |
Citations (3)
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|---|---|---|---|---|
| US4415504A (en) * | 1981-09-21 | 1983-11-15 | Tanabe Seiyaku Co., Ltd. | p-Hydroxyphenylglycine.α-phenylethanesulfonate, process for production thereof and utilization thereof in resolution of p-hydroxyphenylglycine |
| US4519955A (en) * | 1983-03-16 | 1985-05-28 | Tanabe Seiyaku Co., Ltd. | Method for optical resolution of DL-α-amino acid or (±)-α-phenylethanesulfonic acid |
| CN102241555A (en) * | 2010-05-13 | 2011-11-16 | 河北科技大学 | Method for preparing photoactived amino acid through resolution |
-
2012
- 2012-07-20 CN CN2012102519023A patent/CN102757367A/en active Pending
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4415504A (en) * | 1981-09-21 | 1983-11-15 | Tanabe Seiyaku Co., Ltd. | p-Hydroxyphenylglycine.α-phenylethanesulfonate, process for production thereof and utilization thereof in resolution of p-hydroxyphenylglycine |
| US4519955A (en) * | 1983-03-16 | 1985-05-28 | Tanabe Seiyaku Co., Ltd. | Method for optical resolution of DL-α-amino acid or (±)-α-phenylethanesulfonic acid |
| CN102241555A (en) * | 2010-05-13 | 2011-11-16 | 河北科技大学 | Method for preparing photoactived amino acid through resolution |
Non-Patent Citations (1)
| Title |
|---|
| 张志霞，: "不对称转换拆分剂-苯乙磺酸的制备研究", 《河北师范大学硕士学位论文》 * |
Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103787929A (en) * | 2014-03-03 | 2014-05-14 | 济南盛弘医药科技有限公司 | D,L-sulfophenylacetic acid resolution method |
| CN103787929B (en) * | 2014-03-03 | 2015-04-15 | 济南盛弘医药科技有限公司 | D,L-sulfophenylacetic acid resolution method |
| CN110467537A (en) * | 2019-08-08 | 2019-11-19 | 河南新天地药业股份有限公司 | A kind of preparation process of D-HPG |
| CN110467537B (en) * | 2019-08-08 | 2022-10-04 | 河南新天地药业股份有限公司 | Preparation process of L-p-hydroxyphenylglycine |
| CN115850127A (en) * | 2022-11-28 | 2023-03-28 | 湖北省宏源药业科技股份有限公司 | Synthesis method of L-p-hydroxyphenylglycine phenyl ethanesulfonate |
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Application publication date: 20121031 |