CN104277027A - Preparation method of (R)-propylene carbonate - Google Patents
Preparation method of (R)-propylene carbonate Download PDFInfo
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- CN104277027A CN104277027A CN201410492312.9A CN201410492312A CN104277027A CN 104277027 A CN104277027 A CN 104277027A CN 201410492312 A CN201410492312 A CN 201410492312A CN 104277027 A CN104277027 A CN 104277027A
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- preparation
- propylene carbonate
- propanediol
- propylene
- catalyzer
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D317/00—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms
- C07D317/08—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3
- C07D317/10—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3 not condensed with other rings
- C07D317/32—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3 not condensed with other rings with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D317/34—Oxygen atoms
- C07D317/36—Alkylene carbonates; Substituted alkylene carbonates
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
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Abstract
The invention relates to a preparation method of (R)-propylene carbonate and belongs to the technical field of medicine production and the technical field of preparation of a tenofovir intermediate particularly. The preparation method comprises the following steps of: activating a catalyst by adopting methylbenzene and acetic acid in air; mixing epoxy propane and the activated catalyst, then dropwise adding water, then stirring to react under the condition of normal temperature, then distilling out (S)-epoxy propane, and then carrying out reduced pressure distillation to obtain (R)-1,2-propanediol; mixing (R)-1,2-propanediol, carbamide and zinc oxide, reacting till the end under the condition of environmental temperature of 100-120 DEG C, then carrying out the reduced pressure distillation to remove (R)-1,2-propanediol, and then continuously distilling to obtain the (R)-propylene carbonate. The preparation method disclosed by the invention is low in production cost. According to the preparation method, the excessive (R)-1,2-propanediol is recovered to be continuously used, and the used raw material urea is more favorable to clean production in comparison with diethyl carbonate.
Description
Technical field
The invention belongs to medicine doctor production technical field, the particularly preparing technical field of tynofovir intermediate, particularly a kind of preparation method of (R)-propylene carbonate.
Background technology
(R)-propylene carbonate is the key intermediate of the anti-AIDS of synthesis and anti-hepatic-B virus medicine tynofovir (Tenofovir).In recent years, following two kinds of methods are all adopted to produce (R)-propylene carbonate both at home and abroad.
First method: obtain (R)-1,2-propylene glycol from racemic epoxide propane Hydrolysis Resolution, and then react with methylcarbonate or diethyl carbonate the method prepared and produce this product.The methyl alcohol produced in this method and methylcarbonate or ethanol and diethyl carbonate all can azeotropic, should not be separated, so raw material can be caused not utilize completely, cause material cost high (see " study on the synthesis of R-propylene carbonate " of the people such as fourth Warburg Pincus, Chen Yu, luckiness; " sodium methoxide catalyzed synthesis (R) propylene carbonate " of the people such as Xia Jianhui, Xu Zhaohui).
Second method: obtain (R)-propylene oxide from racemic epoxide propane Hydrolysis Resolution, then produce this product with carbon dioxide reaction.This method is high to equipment requirements, and produce dangerous large, productive rate is lower.
Summary of the invention
Technical problem to be solved by this invention is to provide the preparation method of one (R)-propylene carbonate, and present method simple general-purpose, operation is convenient, cost is low, selectivity is high, is convenient to suitability for industrialized production.
The present invention includes following steps:
1) in atmosphere, (S, S)-Salen Co catalyzer, toluene and acetic acid mix and blend are reacted, obtains the solid catalyst after activation;
2) under propylene oxide being mixed be placed on 0 ~ 5 DEG C of envrionment temperature with the solid catalyst after activation, instillation water, again under normal temperature condition stirring reaction to reacting end, then air distillation goes out (S)-propylene oxide, underpressure distillation again, obtain high purity, (the R)-1,2-PD of high optical value;
3) (R)-1,2-PD, urea and zinc oxide being mixed, is react to terminating under the condition of 100 ~ 120 DEG C in envrionment temperature, then (R)-1 is removed in underpressure distillation, 2 propylene glycol, then continue distillation, obtain (R)-propylene carbonate.
Reaction formula of the present invention is as follows:
Compare original production technique, feature of the present invention is:
1, compare sodium methoxide catalyzed synthesis technique, this raw materials technology utilization ratio is higher, and cheap, and production cost reduces greatly.Wherein, can continue to use, the relative diethyl carbonate of raw material urea of use after (R) excessive in building-up process-1,2 propylene glycol reclaims, price wants much cheap, in addition, with regard to environmental protection aspect, is more conducive to cleaner production.
2, compare carbon dioxide process synthesis technique, this technological reaction mild condition, be easy to control, lower to the requirement of conversion unit, the security of chemical process improves greatly.In addition, product yield is higher, can reach more than 92%.
In addition, the mixing mol ratio of described (S, S)-Salen Co catalyzer and acetic acid is 1:7 ~ 8, can cross and make catalyst activation abundant under this ratio.
Described propylene oxide is 0.008 ~ 0.006:2.5 ~ 2.2:1 with the mol ratio that mixes of the solid catalyst after activation, water, and this ratio both can ensure the higher yields of product, also ensured the purity of product.
The mixing mol ratio of described (R)-1,2-PD, urea and zinc oxide is 1:0.6 ~ 1:0.007 ~ 0.01, and this ratio can make urea reaction complete, is convenient to product separation and obtains higher yield.
The reaction times of described step 3) is 10 ~ 20 hours.This reaction times is too short, and reaction intermediate transforms not exclusively, long, has new impurity and generates.
Embodiment
1, the preparation of (R)-1,2-PD:
Take (the S of 0.002 mol (0.833g), S)-Salen Co catalyzer is in the flask of 100 mL, add toluene 18.4ml, then add the AcOH of 14.5mmol (0.87g), be then open in air and stir 0.5h catalyzer is activated.Visible reaction system slowly becomes Vandyke brown by brick-red, and namely catalyzer is activated.Then with vacuum pump, toluene is removed, leave auburn solid, the catalyzer namely after activation.
The propylene oxide of 40g and the catalyzer 0.002mol activated are mixed in flask, by mixed system ice bath to 0 ~ 5 DEG C, slowly drip the water of 5.6g simultaneously, then remove ice bath, react 14 h in stirred at rt for another.After reaction terminates, distill out (S)-propylene oxide prior under normal pressure, then use oil pump underpressure distillation, obtain 25.6g (R)-1,2 propylene glycol, yield 98%.
2, the preparation of (R)-propylene carbonate:
In flask, add (R)-1,2 propylene glycol and 0.5 mol urea of 0.6 mol, add the zinc oxide of 0.005 mol (0.4g), stirring reaction 12h under oil bath 100 ~ 120 DEG C of conditions.
After reaction terminates, underpressure distillation goes out excessive R-1,2 propylene glycol; Continue (the R)-propylene carbonate 47g distilling out synthesis.
(R) yield of-propylene carbonate is 92%.
Claims (5)
1. a preparation method for (R)-propylene carbonate, is characterized in that comprising the following steps:
1) in atmosphere, (S, S)-Salen Co catalyzer, toluene and acetic acid mix and blend are reacted, obtains the catalyzer after activation;
2) under propylene oxide being mixed be placed on 0 ~ 5 DEG C of envrionment temperature with the solid catalyst after activation, instillation water, then stirring reaction is to reacting end under normal temperature condition, then air distillation goes out (S)-propylene oxide, decompression steams (R)-1,2-PD again;
3) (R)-1,2-PD, urea and zinc oxide being mixed, is react to terminating under the condition of 100 ~ 120 DEG C in envrionment temperature, then (R)-1 is removed in underpressure distillation, 2 propylene glycol, then continue distillation, obtain (R)-propylene carbonate.
2. preparation method according to claim 1, is characterized in that the mixing mol ratio of described (S, S)-Salen Co catalyzer and acetic acid is 1:7 ~ 8.
3. preparation method according to claim 1, is characterized in that the solid catalyst after described propylene oxide and activation, the mol ratio that mixes of water is 0.008 ~ 0.006:2.5 ~ 2.2:1.
4. preparation method according to claim 1, is characterized in that the mixing mol ratio of described (R)-1,2-PD, urea and zinc oxide is 1:0.6 ~ 1:0.007 ~ 0.01.
5. preparation method according to claim 1 or 4, is characterized in that the reaction times of described step 3) is 10 ~ 20 hours.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201410492312.9A CN104277027A (en) | 2014-09-24 | 2014-09-24 | Preparation method of (R)-propylene carbonate |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201410492312.9A CN104277027A (en) | 2014-09-24 | 2014-09-24 | Preparation method of (R)-propylene carbonate |
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| Publication Number | Publication Date |
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| CN104277027A true CN104277027A (en) | 2015-01-14 |
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| Application Number | Title | Priority Date | Filing Date |
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| CN201410492312.9A Pending CN104277027A (en) | 2014-09-24 | 2014-09-24 | Preparation method of (R)-propylene carbonate |
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Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN107619405A (en) * | 2017-09-25 | 2018-01-23 | 常熟理工学院 | It is a kind of（R）The preparation method of single thiocarbonic acid propylene |
| CN111875577A (en) * | 2020-08-25 | 2020-11-03 | 湖南亚王医药科技有限公司 | Preparation method of R-propylene carbonate |
| CN111943805A (en) * | 2020-09-16 | 2020-11-17 | 安徽工业大学 | Preparation method of (R) -3-chloro-1, 2-propanediol |
-
2014
- 2014-09-24 CN CN201410492312.9A patent/CN104277027A/en active Pending
Non-Patent Citations (2)
| Title |
|---|
| 丁华平等: "R-碳酸丙烯酯的合成研究", 《徐州工程学院学报(自然科学版)》 * |
| 杜伟超: "尿素与1,2-丙二醇催化合成碳酸丙烯酯反应研究", 《中国优秀硕士学位论文全文数据库工程科技I辑》 * |
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN107619405A (en) * | 2017-09-25 | 2018-01-23 | 常熟理工学院 | It is a kind of（R）The preparation method of single thiocarbonic acid propylene |
| CN111875577A (en) * | 2020-08-25 | 2020-11-03 | 湖南亚王医药科技有限公司 | Preparation method of R-propylene carbonate |
| CN111875577B (en) * | 2020-08-25 | 2021-11-09 | 湖南亚王医药科技有限公司 | Preparation method of R-propylene carbonate |
| CN111943805A (en) * | 2020-09-16 | 2020-11-17 | 安徽工业大学 | Preparation method of (R) -3-chloro-1, 2-propanediol |
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Application publication date: 20150114 |