CN104003850A - Preparation method of 2-chloroethoxy-2-ethyoxylethanol - Google Patents
Preparation method of 2-chloroethoxy-2-ethyoxylethanol Download PDFInfo
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- CN104003850A CN104003850A CN201410212574.5A CN201410212574A CN104003850A CN 104003850 A CN104003850 A CN 104003850A CN 201410212574 A CN201410212574 A CN 201410212574A CN 104003850 A CN104003850 A CN 104003850A
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- chloroethoxy
- oxyethyl group
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- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C41/00—Preparation of ethers; Preparation of compounds having groups, groups or groups
- C07C41/01—Preparation of ethers
- C07C41/02—Preparation of ethers from oxiranes
- C07C41/03—Preparation of ethers from oxiranes by reaction of oxirane rings with hydroxy groups
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Abstract
The invention discloses a preparation method of 2-chloroethoxy-2-ethyoxylethanol. The preparation method comprises the steps: with 2-chloroethoxy and ethylene oxide as raw materials, performing a reaction in the presence of a catalyst to firstly obtain 2-ethyoxylethanol, removing the remaining solvent, namely a reactant 2-chlorohydrin, making the 2-ethyoxylethanol continuously react with the re-added ethylene oxide to obtain a target product 2-chloroethoxy-2-ethyoxylethanol. The preparation method has the advantages of being easy to operate during reaction, mild in system, less in side reactions, high in content and yield of products, and less in pollutants generated during the reaction.
Description
Technical field
The invention belongs to chemical field, relate in particular to a kind of medicine intermediate 2-chloroethoxy-2-oxyethyl group di-alcohol, specifically a kind of preparation method of 2-chloroethoxy-2-oxyethyl group di-alcohol.
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Background technology
2-chloroethoxy-2-oxyethyl group di-alcohol, is called for short CEEE, and outward appearance is colourless transparent liquid, and CAS registration number is [5197-62-6], and structural formula is:
2-chloroethoxy-2-oxyethyl group di-alcohol, as the intermediate of the medicines such as Pranedipine Tartrate and LJP-920, is a kind of important intermediate of medication chemistry.
Its synthetic method mainly contains following three kinds:
A: directly carry out etherification reaction by triethylene glycol and HCl and prepare 2-chloroethoxy-2-oxyethyl group di-alcohol, synthetic route is as follows:
The method raw material is easy to get, but side reaction is many, poor selectivity, and yield is low, and cost is higher, is therefore difficult to application and suitability for industrialized production.
B: reacted with HCl by glycol ether, first make 2-chloroethoxy ethanol, then carry out second step with oxyethane and react, preparation 2-chloroethoxy-2-oxyethyl group di-alcohol, synthetic route is as follows:
The method raw material is easy to get, but exists reaction preference poor, and side reaction is many, and yield is low, high in cost of production problem.
C: prepare 2-chloroethoxy-2-oxyethyl group di-alcohol taking Isosorbide-5-Nitrae-dioxane as raw material, synthetic route is as follows:
The method, at present in theoretical research stage, is not suitable for suitability for industrialized production.
The subject matter of above-mentioned the whole bag of tricks is poor selectivity, and yield is low, and preparation difficulty, is unfavorable for suitability for industrialized production.
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Summary of the invention
For the defect existing in above-mentioned prior art, technical problem to be solved by this invention is to provide a kind of preparation method of 2-chloroethoxy-2-oxyethyl group di-alcohol, and described this method will solve preparation method's poor selectivity of the prior art, yield is low, preparation is difficult, be unfavorable for the technical problem of suitability for industrialized production.
The preparation method of a kind of 2-chloroethoxy-2-of the present invention oxyethyl group di-alcohol, comprises the following steps:
1) take reactant ethylene chlorhydrin and first oxyethane, the mol ratio of ethylene chlorhydrin and first oxyethane is 7～9:1, and ethylene chlorhydrin and first oxyethane react under catalyzer existence condition, generates intermediate product 2-chloroethoxy ethanol;
2) material that in step 1), reaction finishes is sloughed to excessive ethylene chlorhydrin under vacuum decompression condition;
3) by step 2) in slough material after ethylene chlorhydrin and continue to react with second batch oxyethane under catalyzer existence condition, described 2-chloroethoxy ethanol and the mol ratio of second batch oxyethane are 1:1.0～1.4;
4) material that in step 3), reaction finishes is distilled under vacuum decompression condition, collect middle runnings, obtain 2-chloroethoxy-2-oxyethyl group di-alcohol crude product;
5) by the 2-chloroethoxy-2-oxyethyl group di-alcohol crude product obtaining in step 4), under vacuum decompression condition, carry out rectifying, collect 2-chloroethoxy-2-oxyethyl group di-alcohol cut, obtain 2-chloroethoxy-2-oxyethyl group di-alcohol product.
Concrete, in step 1), ethylene chlorhydrin is both as reactant, again as solvent.
Further, in described step 1), step 3), used catalyst is boron trifluoride diethyl etherate, and catalyzer add-on is 0.3%～0.6% of material system total mass, and the add-on of described catalyzer is preferably 0.45%.
Further, in described step 1), temperature of reaction is 35-55 DEG C, and the reaction times is 1.5～2 hours; Preferably temperature is 40-50 DEG C.
Further, described step 2) in vacuum tightness be 10-15mmHg, precipitation temperature is 100～110 DEG C.
Further, in described step 3), temperature of reaction is 40-55 DEG C, and the reaction times is 1.5-2 hour; Preferably temperature is 45-55 DEG C.
Further, in described step 4), vacuum distillation temperature is 105-130 DEG C, and vacuum tightness is 5-10mmHg.
Further, in described step 5), vacuum distillation temperature is 108-125 DEG C, and vacuum tightness is 5-10mmHg.
The reaction equation the present invention relates to is as follows:
The present invention, taking ethylene chlorhydrin as raw material, prepares 2-chloroethoxy-2-oxyethyl group di-alcohol by two step etherification reactions, efficiently solves the many and high problem of content of dopant species that direct chlorination method brings.The crude product purity of its 2-chloroethoxy-2-oxyethyl group di-alcohol of preparation method provided by the invention can reach more than 93%, has improved the purity of product, meanwhile, the transformation efficiency of reaction and yield, yield can reach more than 70%, and process costs is significantly reduced.Because reactant can be used as solvent, and solvent can be recycled, and therefore there is no extra solvent reclamation cost; In reaction process, without waste water and other pollutent, three wastes processing cost is reduced greatly, technique is environmental protection more.
The present invention compares with prior art, and its technical progress is significant.Method of the present invention has improved content and the yield of product, has reduced again pollution, is applicable to suitability for industrialized production.
Brief description of the drawings
Fig. 1 is the infrared spectrogram of 2-chloroethoxy-2-oxyethyl group di-alcohol of preparing of the present invention.
Fig. 2 is the hydrogen nuclear magnetic spectrogram of 2-chloroethoxy-2-oxyethyl group di-alcohol of preparing of the present invention.
Fig. 3 is the mass spectrum of 2-chloroethoxy-2-oxyethyl group di-alcohol of preparing of the present invention.
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Embodiment
Embodiment 1
In 1000ml there-necked flask, add ethylene chlorhydrin 685g (8.5mol), catalyzer 3.3g, start agitator and well heater, be warming up to 40 DEG C (for making temperature of reaction maintain 40-50 DEG C, gate ring oxidative ethane to pass into speed, can adopt if desired water-bath temperature control), in flask, slowly pass into 44g oxyethane, the time of passing into is 1.5-2h.For making to react completely, after logical oxyethane finishes, continue stirring reaction 0.5h.Stir and finish, heat up, under reduced pressure, slough excessive ethylene chlorhydrin, vacuum tightness 0.075mPa(water rushes pump), last precipitation temperature is 105 DEG C, and collecting the about 592g(of ethylene chlorhydrin can recycle), in flask, obtain taking intermediate product 2-chloroethoxy ethanol as main material.
Material in there-necked flask is cooled to 45-50 DEG C, adds 0.7g boron trifluoride diethyl etherate, under stirring, pass into 46.2g(1.05mol) oxyethane, the time of passing into is 1.5-2h, for making temperature of reaction maintain 45-55 DEG C, gate ring oxidative ethane to pass into speed, can adopt if desired water-bath temperature control.Meanwhile, for making to react completely, after logical oxyethane finishes, continue stirring reaction 0.5h.After reaction finishes, heat up, under vacuum decompression, distill, getting middle runnings (cut temperature 115-123 DEG C, vacuum tightness 10mmHg) is colourless transparent liquid.By rectifying under the middle runnings vacuum decompression condition of collecting, getting middle runnings (cut temperature 118-121 DEG C, vacuum tightness 10mmHg) is colourless transparent liquid, 123.6g, gas phase content 97.7%, total 73.3%.
Product structure is confirmed: in annex 1 infrared spectrogram, the absorption peak at 3416 places is hydroxyl (OH), and the absorption peak at 1105 places is ehter bond (C-O-C), and 2871 places are hydrocarbon key (CH), and 1064 places are-CH
2-OH.In annex 2 proton magnetic spectrums, 3.685 is peak-to-peak signals of hydrogen on middle two methylene radical of 2-chloroethoxy-2-oxyethyl group di-alcohol structural formula, the 3.763rd, the peak-to-peak signal of hydrogen on the methylene radical adjacent with C-Cl, the 3.735th, the peak-to-peak signal of hydrogen on the methylene radical joining with hydroxyl, the 3.643rd, the peak-to-peak signal of hydrogen on the methylene radical joining with chlorine, the 3.613rd, the peak-to-peak signal of hydrogen on the methylene radical adjacent with C-0H.In annex 3 mass spectrums, 169 molecular ion peak can obviously be confirmed the molecular weight of this material.The structure that can obtain thus 2-chloroethoxy-2-oxyethyl group di-alcohol meets the conclusion of collection of illustrative plates.
Embodiment 2
In 1000ml there-necked flask, add ethylene chlorhydrin 685g (recycling 592g+93g new) (8.5mol), catalyzer 3.3g, start agitator and well heater, be warming up to 40 DEG C (for making temperature of reaction maintain 40-50 DEG C, gate ring oxidative ethane to pass into speed, can adopt if desired water-bath temperature control), in flask, slowly pass into 44g oxyethane, the time of passing into is 1.5-2h.For making to react completely, after logical oxyethane finishes, continue stirring reaction 0.5h.Stir and finish, start to heat up, under reduced pressure, slough excessive ethylene chlorhydrin, vacuum tightness 0.075mPa(water rushes pump), last precipitation temperature is 105 DEG C, collects the about 587g of ethylene chlorhydrin, can continue to apply mechanically, be taking intermediate product 2-chloroethoxy ethanol as main material in flask.
Material in there-necked flask is cooled to 45-50 DEG C, adds 0.7g boron trifluoride diethyl etherate, under stirring, pass into 46.2g(1.05mol) oxyethane, the time of passing into is 1.5-2h, for making temperature of reaction maintain 45-55 DEG C, gate ring oxidative ethane to pass into speed, can adopt if desired water-bath temperature control.For making to react completely, after logical oxyethane finishes, continue stirring reaction 0.5h.After reaction finishes, start to heat up, under vacuum decompression, distill, getting middle runnings (cut temperature 115-123 DEG C, vacuum tightness 10mmHg) is colourless transparent liquid.By middle runnings rectifying under vacuum decompression condition, getting middle runnings (cut temperature 118-121 DEG C, vacuum tightness 10mmHg) is colourless transparent liquid, 122.3g, gas phase content 97.8 %, total recovery 72.5%.
Embodiment 3
Catalyst levels in embodiment 2 is turned down to 0.3% of material total amount, and charge ratio and reaction conditions are in the same manner as in Example 2, obtain product 116.7g after rectifying, gas phase content 97.6%, total recovery 69.2%.
Claims (6)
1. a preparation method for 2-chloroethoxy-2-oxyethyl group di-alcohol, is characterized in that comprising the following steps:
1) take reactant ethylene chlorhydrin and first oxyethane, the mol ratio of ethylene chlorhydrin and first oxyethane is 7～9:1, and ethylene chlorhydrin and first oxyethane react under catalyzer existence condition, generates intermediate product 2-chloroethoxy ethanol;
2) material that in step 1), reaction finishes is steamed to excessive ethylene chlorhydrin under vacuum decompression condition;
3) by step 2) in slough material after ethylene chlorhydrin and continue to react with second batch oxyethane under catalyzer existence condition, described 2-chloroethoxy ethanol and the mol ratio of second batch oxyethane are 1:1.0～1.4;
4) material that in step 3), reaction finishes is distilled under vacuum decompression condition, collect middle runnings, obtain 2-chloroethoxy-2-oxyethyl group di-alcohol crude product;
5) by the 2-chloroethoxy-2-oxyethyl group di-alcohol crude product obtaining in step 4), under vacuum decompression condition, carry out rectifying, collect 2-chloroethoxy-2-oxyethyl group di-alcohol cut, obtain 2-chloroethoxy-2-oxyethyl group di-alcohol.
2. the preparation method of a kind of 2-chloroethoxy-2-oxyethyl group di-alcohol according to claim 1, it is characterized in that: in described step 1), step 3), used catalyst is boron trifluoride diethyl etherate, catalyzer add-on is the 0.3%-0.6% of material system total mass.
3. the preparation method of a kind of 2-chloroethoxy-2-oxyethyl group di-alcohol according to claim 1, is characterized in that: in described step 1), temperature of reaction is 35-55 DEG C, and the reaction times is 1.5-2 hour.
4. the preparation method of a kind of 2-chloroethoxy-2-oxyethyl group di-alcohol according to claim 1, is characterized in that: in described step 3), temperature of reaction is 40-55 DEG C, and the reaction times is 1.5-2 hour.
5. the preparation method of a kind of 2-chloroethoxy-2-oxyethyl group di-alcohol according to claim 1, is characterized in that: in described step 4), vacuum distillation temperature is 105-130 DEG C, and vacuum tightness is 5-10mmHg.
6. the preparation method of a kind of 2-chloroethoxy-2-oxyethyl group di-alcohol according to claim 1, is characterized in that: in described step 5), vacuum distillation temperature is 108-125 DEG C, and vacuum tightness is 5-10mmHg.
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| CN201410212574.5A CN104003850B (en) | 2014-05-20 | 2014-05-20 | A kind of preparation method of 2-chloroethoxy-2-oxyethyl group di-alcohol |
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN106554261A (en) * | 2016-11-25 | 2017-04-05 | 河南龙都石油化工有限公司 | 1 halopropane glycol ether and preparation method thereof |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4283577A (en) * | 1978-09-29 | 1981-08-11 | Produits Chimiques Ugine Kuhlmann | Method for making ethylene chlorohydrin |
| JPS5967235A (en) * | 1982-10-07 | 1984-04-16 | Mitsui Toatsu Chem Inc | Preparation of 2-(2'-chloroethoxy)ethanol |
| JPH02256634A (en) * | 1988-12-05 | 1990-10-17 | Nisso Maruzen Chem Kk | Production of high-purity 2-(2'-chloroethoxy)ethanol |
-
2014
- 2014-05-20 CN CN201410212574.5A patent/CN104003850B/en active Active
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4283577A (en) * | 1978-09-29 | 1981-08-11 | Produits Chimiques Ugine Kuhlmann | Method for making ethylene chlorohydrin |
| JPS5967235A (en) * | 1982-10-07 | 1984-04-16 | Mitsui Toatsu Chem Inc | Preparation of 2-(2'-chloroethoxy)ethanol |
| JPH02256634A (en) * | 1988-12-05 | 1990-10-17 | Nisso Maruzen Chem Kk | Production of high-purity 2-(2'-chloroethoxy)ethanol |
Non-Patent Citations (1)
| Title |
|---|
| 余一成: "安他乐生产路线的研究", 《药学学报》 * |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN106554261A (en) * | 2016-11-25 | 2017-04-05 | 河南龙都石油化工有限公司 | 1 halopropane glycol ether and preparation method thereof |
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Inventor after: Jiang Jibo Inventor after: Huang Qi Inventor after: He Huihong Inventor after: Zhu Jun Inventor after: Ma Peng Inventor after: Han Sheng Inventor after: Ye Fengying Inventor after: Yu Fei Inventor after: Liu Cheng Inventor after: Chen Yongyue Inventor after: Liu Yafeng Inventor after: Liu Fan Inventor before: Han Sheng Inventor before: Ma Peng Inventor before: Yu Fei Inventor before: Liu Cheng Inventor before: Chen Yongyue Inventor before: Liu Yafeng Inventor before: He Huihong Inventor before: Zhu Jun |
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Effective date of registration: 20181129 Address after: Room 3270, Building 1, 215 Union North Road, Fengxian District, Shanghai, 201417 Patentee after: Shanghai wisdom Medical Technology Service Co., Ltd. Address before: 200235 No. 120, Xuhui District, Shanghai, Caobao Road Patentee before: Shanghai Institute of Technology |
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Effective date of registration: 20210128 Address after: Room 301, 965 Halley Road, Zhangjiang hi tech park, Pudong New Area, Shanghai 201203 Patentee after: SHANGHAI CHEMPARTNER Co.,Ltd. Address before: Room 3270, Building 1, 215 Union North Road, Fengxian District, Shanghai, 201417 Patentee before: Shanghai wisdom Medical Technology Service Co.,Ltd. |
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