CN101838249A - Method for preparing high-purity guaiacol glycidyl ether - Google Patents
Method for preparing high-purity guaiacol glycidyl ether Download PDFInfo
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- CN101838249A CN101838249A CN201010144102A CN201010144102A CN101838249A CN 101838249 A CN101838249 A CN 101838249A CN 201010144102 A CN201010144102 A CN 201010144102A CN 201010144102 A CN201010144102 A CN 201010144102A CN 101838249 A CN101838249 A CN 101838249A
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- glycidyl ether
- guaiacol
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- guaiacol glycidyl
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D301/00—Preparation of oxiranes
- C07D301/27—Condensation of epihalohydrins or halohydrins with compounds containing active hydrogen atoms
- C07D301/28—Condensation of epihalohydrins or halohydrins with compounds containing active hydrogen atoms by reaction with hydroxyl radicals
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D303/00—Compounds containing three-membered rings having one oxygen atom as the only ring hetero atom
- C07D303/02—Compounds containing oxirane rings
- C07D303/12—Compounds containing oxirane rings with hydrocarbon radicals, substituted by singly or doubly bound oxygen atoms
- C07D303/18—Compounds containing oxirane rings with hydrocarbon radicals, substituted by singly or doubly bound oxygen atoms by etherified hydroxyl radicals
- C07D303/20—Ethers with hydroxy compounds containing no oxirane rings
- C07D303/24—Ethers with hydroxy compounds containing no oxirane rings with polyhydroxy compounds
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- Chemical Kinetics & Catalysis (AREA)
- Epoxy Compounds (AREA)
Abstract
The invention discloses a method for preparing high-purity guaiacol glycidyl ether, which comprises the following steps of: condensing guaiacol and epoxy chloropropane under the action of a base; performing reduced pressure distillation after the reaction to obtain a crude product of the guaiacol glycidyl ether; and re-crystallizing the crude product by using a C1-C4 lower alcohol solvent to obtain the guaiacol glycidyl ether of which the purity (GC) is over 99.5 percent. The method for preparing the high-purity guaiacol glycidyl ether has the advantages of high yield, good quality, convenient operation and low requirements on equipment, and is very suitable for industrial production.
Description
(1) technical field
The present invention relates to a kind of preparation high purity 1-(2-methoxyl group phenoxy group)-2, the method for 3-propylene oxide (being called guaiacol glycidyl ether among the present invention).
(2) background technology
Guaiacol glycidyl ether is widely used as the intermediate of ranolazine and moprolol, and its structural formula is as follows:
This product mainly is that condensation in the presence of alkali forms by methyl catechol and epoxy chloropropane, and reaction formula is as follows:
Be through two-step reaction in the real reaction; Epoxy chloropropane elder generation's open loop and methyl catechol condensation, and then under the effect of alkali, slough a hydrogenchloride formation oxirane ring.
Report that in patent GB2216520 epoxy chloropropane and methyl catechol reaction finishing back are extracted earlier with the methylene dichloride dilution again, distillation earlier obtains crude product, and fractionation obtains product under high vacuum then.Adopt this method, need to consume a large amount of methylene dichloride, very big to environmental influence, and adopt vacuum fractionation under the high temperature in the purification process, to the equipment requirements harshness.
Describe in WO2008047388, adopt toluene as solvent in the reaction process, epoxy chloropropane and methyl catechol reaction wash with water with methylbenzene extraction after reaction finishes again, and distillation obtains product under 130～150 ℃ of (3bar) situations then.Relate to the big problem of quantity of solvent in this method equally, and, do solvent emulsification easily in the process of extracting with toluene because product density is bigger than water.Also do not mention purification process in this patent, the product purity that obtains has only about 96%.
Under high temperature, all do not mention other process for purification at present in disclosed other document the underpressure distillation.And polymerization easily takes place in product under the high temperature, adopts this method, and degree of purity of production is difficult to improve, and yield is also lower.
(3) summary of the invention
The object of the present invention is to provide a kind of product purity height, help the preparation method of industrialization, low-cost guaiacol glycidyl ether.
In order to obtain highly purified product, several Key Points is arranged in the building-up process of this product: (1) raw material needs to add alkali in reaction process, and in order to control alkali residual in product, the alkali of selecting for use should well separate with product.(2) after reaction finished, the impurity that forms in raw material that unreacted finishes and the reaction process should well separate with product.
In order to control the cost of product, at first should choose cheap material as far as possible, secondly the input on production unit should obtain better controlled, and technology should handled easily, and the intact raw material of unreacted is wanted can reclaim, the solvent use of trying not.
Comprehensive above two aspects, the alkali of using in the reaction selects for use inorganic base that apparent in view advantage is arranged in this respect; Use inorganic base in the reaction, use two phase reaction, can effectively control alkaloids residual in product; Owing to the major impurity that forms in two raw materials and the reaction process all is a liquid at room temperature, and product at room temperature is a solid, therefore adopts the crystalline mode that the purity that improves product is had extraordinary effect; Directly adopt epoxy chloropropane as solvent in the reaction, react the directly recovery set usefulness of back solvent that finishes, environmental pollution is little, and cost is also low.
According to more than, the guaiacol glycidyl ether preparation method who relates among the present invention carries out as follows:
(1) methyl catechol is dissolved in the excessive epoxy chloropropane.Carry out condensation reaction then under the effect of the aqueous solution of mineral alkali and phase-transfer catalyst, after reaction finished, branch vibration layer reclaimed excessive epoxy chloropropane by underpressure distillation.Continue to concentrate the cut of collecting 148～153 ℃/1.33KPa and obtain the guaiacol glycidyl ether crude product.
(2) crude product that step (1) is obtained obtains highly purified guaiacol glycidyl ether with the organic solvent recrystallization.
In step (1), the amount of epoxy chloropropane can be chosen as 1～8 equivalent of methyl catechol, is preferably 2～5 equivalents.Mineral alkali can be selected yellow soda ash, salt of wormwood, sodium hydroxide, potassium hydroxide etc., preferred sodium hydroxide and potassium hydroxide.The concentration of aqueous solution of alkali can select 10%～50%.Phase-transfer catalyst can be selected Tetrabutyl amonium bromide, benzyltriethylammoinium chloride, 4-butyl ammonium hydrogen sulfate, tetrabutylammonium chloride etc.Temperature of reaction is 20 ℃～80 ℃, and wherein preferred temperature is 30～60 ℃.Reaction times is 1～10 hour, and preferable range is 2～5 hours.
In step (2), the organic solvent class can be selected alcohols, ester class and ethers, wherein preferred lower alcohols.C1～C4 lower alcohols solvents such as methyl alcohol, ethanol, n-propyl alcohol, Virahol, butanols more preferably.The crystalline quantity of solvent is 1～10ml/g (a guaiacol glycidyl ether crude product), wherein preferred 2～5ml/g (guaiacol glycidyl ether crude product).Crystallization can natural stirring and crystallizing also can add crystal seed and induce crystallization, for crystallization control speed guarantees preferably to add the purity of product crystal seed and induce crystallization.
Present method yield height, quality is good, and is easy to operate, low for equipment requirements, is a kind of method for preparing high-purity guaiacol glycidyl ether that is fit to very much suitability for industrialized production.
(4) embodiment
Following implementations can help to understand the present invention, but protection scope of the present invention is not limited thereto.
Embodiment 1: preparation guaiacol glycidyl ether crude product
Methyl catechol 44.4g drops in the 250ml reaction flask, adds epoxy chloropropane 99.8g then, and Tetrabutyl amonium bromide 1.16g stirs.The sodium hydroxide solution 64g of dropping 25% drips and finishes, 50～55 ℃ of reactions of controlled temperature 2 hours.After reaction finishes, wash once layering then, the epoxy chloropropane that the organic phase reclaim under reduced pressure is excessive with water.After recovery finishes, heat up and continue distillation, the cut of collecting 148～153 ℃/1.33KPa gets colourless transparent liquid 45.1g, yield 70%, purity: 98% (GC mensuration)
Embodiment 2: the preparation high-purity guaiacol glycidyl ether
30g guaiacol glycidyl ether crude product adds in the 90ml ethanol, is heated to 40 ℃, and it is molten clear to be stirred to solution.Filter, filtrate slowly is cooled to 20 ℃, adds crystal seed, maintains the temperature at 18～20 ℃ of following stirring and crystallizing 2 hours, then temperature is slowly reduced to 0～5 ℃ and stirs 1 hour, filters.25 ℃ of vacuum-dryings of filter cake got white solid 25.5g, yield 85%, purity: 99.8% (GC mensuration) in 12 hours.
Embodiment 3: the preparation high-purity guaiacol glycidyl ether
30g guaiacol glycidyl ether crude product adds in the 90ml methyl alcohol, is heated to 40 ℃, and it is molten clear to be stirred to solution.Filter, filtrate slowly is cooled to 14 ℃, adds behind the crystal seed in 14～16 ℃ of following stirring and crystallizing 2 hours, then temperature is slowly reduced to 0～5 ℃ and stirred 1 hour, filter, 25 ℃ of vacuum-dryings of filter cake got white solid 24g in 12 hours, yield 80%, purity: 99.6% (GC mensuration).
Embodiment 4: the preparation high-purity guaiacol glycidyl ether
30g guaiacol glycidyl ether crude product adds in the 120ml Virahol, is heated to 50 ℃, and it is molten clear to be stirred to solution.Filter, filtrate slowly is cooled to 20 ℃, adds behind the crystal seed in 15～20 ℃ of following stirring and crystallizing 2 hours, then temperature is slowly reduced to 0～5 ℃ and stirred 1 hour, filter, 25 ℃ of vacuum-dryings of filter cake got white solid 26.4g in 12 hours, yield 88%, purity: 99.5% (GC mensuration).
Embodiment 5: the preparation high-purity guaiacol glycidyl ether
30g guaiacol glycidyl ether crude product adds in the 120ml n-propyl alcohol, is heated to 50 ℃, and it is molten clear to be stirred to solution.Filter, filtrate slowly is cooled to 20 ℃, adds behind the crystal seed in 15～20 ℃ of following stirring and crystallizing 2 hours, then temperature is slowly reduced to 0～5 ℃ and stirred 1 hour, filter, 25 ℃ of vacuum-dryings of filter cake got white solid 26.1g in 12 hours, yield 87%, purity: 99.7% (GC mensuration).
Claims (6)
1. method for preparing high-purity guaiacol glycidyl ether, described method is: the condensation under the effect of the aqueous solution of mineral alkali and phase-transfer catalyst of methyl catechol and epoxy chloropropane, reaction finishes the back underpressure distillation and obtains the guaiacol glycidyl ether crude product, and this crude product is obtained highly purified guaiacol glycidyl ether with the lower alcohols solvent recrystallization.
2. the method for claim 1 is characterized in that alkali is aqueous sodium hydroxide solution, potassium hydroxide aqueous solution, aqueous sodium carbonate; Preferred sodium hydroxide and potassium hydroxide.
3. method as claimed in claim 2, the concentration of aqueous solution of alkali can select 10%～50%.
4. the method for claim 1, phase-transfer catalyst can be selected Tetrabutyl amonium bromide, benzyltriethylammoinium chloride, 4-butyl ammonium hydrogen sulfate, tetrabutylammonium chloride etc.
5. the method for claim 1 is characterized in that described lower alcohol is methyl alcohol, ethanol, n-propyl alcohol, Virahol, butanols.
6. method as claimed in claim 5 is characterized in that the crystalline quantity of solvent is 1～10ml/g (a guaiacol glycidyl ether crude product), wherein preferred 2～5ml/g (guaiacol glycidyl ether crude product).
Priority Applications (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201010144102.2A CN101838249B (en) | 2010-03-19 | 2010-03-19 | A kind of method preparing high-purity guaiacol glycidyl ether |
| PCT/CN2010/073337 WO2011113228A1 (en) | 2010-03-19 | 2010-05-28 | A process for preparing guaiacol glycidyl |
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| CN201010144102.2A CN101838249B (en) | 2010-03-19 | 2010-03-19 | A kind of method preparing high-purity guaiacol glycidyl ether |
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| CN101838249A true CN101838249A (en) | 2010-09-22 |
| CN101838249B CN101838249B (en) | 2015-08-19 |
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Cited By (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2011113228A1 (en) * | 2010-03-19 | 2011-09-22 | 浙江华海药业股份有限公司 | A process for preparing guaiacol glycidyl |
| CN102558097A (en) * | 2011-12-27 | 2012-07-11 | 辅仁药业集团有限公司 | Improved method for synthesizing ranolazine |
| CN102964259A (en) * | 2012-12-11 | 2013-03-13 | 上海奥博生物医药技术有限公司 | Preparation method of related substance E of metoprolol |
| CN104262586A (en) * | 2014-10-22 | 2015-01-07 | 中国科学院上海有机化学研究所 | Epoxy resin with high modulus and high glass transition temperature as well as preparation and application thereof |
| WO2016065576A1 (en) * | 2014-10-30 | 2016-05-06 | Tianjin Weijie Pharmaceutical Co., Ltd. | Process for preparation of high purity guaiacol glycidyl ether |
| CN106957426A (en) * | 2017-04-12 | 2017-07-18 | 浩力森化学科技（江苏）有限公司 | A kind of functional resin for lifting cation-type water-thinned anticorrosion with coat covering power and preparation method thereof |
| CN111440131A (en) * | 2020-04-27 | 2020-07-24 | 江苏惠利生物科技有限公司 | Method for refining easy-to-decompose guaiacol glycidyl ether |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| CN101838249B (en) * | 2010-03-19 | 2015-08-19 | 浙江华海药业股份有限公司 | A kind of method preparing high-purity guaiacol glycidyl ether |
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Cited By (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2011113228A1 (en) * | 2010-03-19 | 2011-09-22 | 浙江华海药业股份有限公司 | A process for preparing guaiacol glycidyl |
| CN102558097A (en) * | 2011-12-27 | 2012-07-11 | 辅仁药业集团有限公司 | Improved method for synthesizing ranolazine |
| CN102964259A (en) * | 2012-12-11 | 2013-03-13 | 上海奥博生物医药技术有限公司 | Preparation method of related substance E of metoprolol |
| CN104262586A (en) * | 2014-10-22 | 2015-01-07 | 中国科学院上海有机化学研究所 | Epoxy resin with high modulus and high glass transition temperature as well as preparation and application thereof |
| WO2016065576A1 (en) * | 2014-10-30 | 2016-05-06 | Tianjin Weijie Pharmaceutical Co., Ltd. | Process for preparation of high purity guaiacol glycidyl ether |
| CN106957426A (en) * | 2017-04-12 | 2017-07-18 | 浩力森化学科技（江苏）有限公司 | A kind of functional resin for lifting cation-type water-thinned anticorrosion with coat covering power and preparation method thereof |
| CN106957426B (en) * | 2017-04-12 | 2019-01-25 | 浩力森化学科技（江苏）有限公司 | A kind of functional resin and preparation method thereof promoting cation-type water-thinned anticorrosion with coat covering power |
| CN111440131A (en) * | 2020-04-27 | 2020-07-24 | 江苏惠利生物科技有限公司 | Method for refining easy-to-decompose guaiacol glycidyl ether |
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| Publication number | Publication date |
|---|---|
| WO2011113228A1 (en) | 2011-09-22 |
| CN101838249B (en) | 2015-08-19 |
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