CN101967092A - Method for synthesizing 2,6-dimethyl phenoxyacetic acid - Google Patents
Method for synthesizing 2,6-dimethyl phenoxyacetic acid Download PDFInfo
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- CN101967092A CN101967092A CN2010102163289A CN201010216328A CN101967092A CN 101967092 A CN101967092 A CN 101967092A CN 2010102163289 A CN2010102163289 A CN 2010102163289A CN 201010216328 A CN201010216328 A CN 201010216328A CN 101967092 A CN101967092 A CN 101967092A
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- dimethyl benzene
- dimethyl
- xylenol
- alkali
- fluoroacetic acid
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Abstract
The invention discloses a method for synthesizing 2,6-dimethyl phenoxyacetic acid, comprising the following steps of: (1) adding 2,6-dimethyl phenol to an alkali aqueous solution, wherein the 2,6-dimethyl phenol and alkali are added in the mole ratio of 0.5-1.0:1.0; (2) stirring to dissolve the mixture, then filtering after sufficient reaction, increasing the temperature of a filtering material and dewatering to obtain 2,6-dimethyl phenolate; (3) mixing the 2,6-dimethyl phenolate and chloroacetic acid in the mole ratio of 0.5-1.0:1.0, heating till the 2,6-dimethyl phenolate and the chloroacetic acid are completely melted, and reacting in an inert gas atmosphere; (4) after the reaction is finished, cooling to room temperature, adding water or alkali liquor for washing, and filtering to obtain a crude product; and (5) recrystallizing the crude product to obtain a 2,6-dimethyl phenoxyacetic acid pure product. The synthesizing method has the advantages of simple and convenient operation, short reaction time, easy postprocessing, few side product, high productivity, and the like.
Description
Technical field
The present invention relates to a kind of improved synthetic method, specifically be meant 2, the synthetic method of 6-dimethyl benzene fluoroacetic acid.
Background technology
2,6-dimethyl benzene fluoroacetic acid is a very important intermediate of anti-AIDS drug rltonavir, and its structural formula is as follows:
Introduced two kind 2 among the patent EP0876353A1, the synthetic method of 6-dimethyl benzene fluoroacetic acid:
1) by 2, the 6-xylenol forms by becoming the ether reaction with Mono Chloro Acetic Acid, and the concrete operations step is as follows:
In there-necked flask, add 2,6-xylenol 102.8g (0.842mol), Mono Chloro Acetic Acid 159.6g (1.68mol) and water 1000ml, stirring and dissolving.Slowly add aqueous sodium hydroxide solution 500ml, reflux then.Add Mono Chloro Acetic Acid 79.4g (0.84mol) and sodium hydroxide solution 200ml after two hours.After 19 hours, add Mono Chloro Acetic Acid 39.8g (0.42mol) and sodium hydroxide solution 100ml, continue to reflux, up to 2, the 6-xylenol runs out of.Ice-water bath cooling reaction flask is used salt acid for adjusting pH value to 1 then, can be observed precipitation and produces, and stirs and filters then in 1 hour.The gained solid matter is dissolved in the hot water, and crystallisation by cooling obtains white solid product then.As mentioned above, in this invention 2, the 6-xylenol is dispersed in the solution, and is bigger with the Mono Chloro Acetic Acid difficulty that reacts, therefore, this method needs continual additional Mono Chloro Acetic Acid and sodium hydroxide, and process is loaded down with trivial details, long reaction time, by product is many, and molar yield is greatly about about 74%.
2) by 2,6-xylenol and ethyl bromoacetate react 2,6-dimethyl phenoxy ethyl acetate is sloughed ester group through the lithium hydroxide hydrolysis again and is got product, the concrete operations step is as follows:
With 2,6-xylenol 8.0g (66mmol) is dissolved in the 600ml dioxane, and (18.2ml 164mmol), reaches cesium carbonate 58g (176mmol) to add ethyl bromoacetate then therein.Reacted also reflux 18 hours, and be cooled to room temperature, filter and use the silicagel column purifying then.Products therefrom 2,6-dimethyl phenoxy ethyl acetate 5.15g (24.7mmol) are dissolved in 170ml methyl alcohol and the 56ml water, add the 5.3g lithium hydroxide down at 0 ℃ then, and mixed solution at room temperature stirs 1.5h, vacuum concentration.Gained concentrated solution 0.5M hcl acidifying, then with ethyl acetate 300ml extraction, organic layer is concentrated into dried white solid.There is the starting material costliness in this method, pollutes greatly, and is not suitable for the problem of suitability for industrialized production.
Summary of the invention
The invention provides a kind ofly 2, the synthetic method of 6-dimethyl benzene fluoroacetic acid is in order to solve the above-mentioned problems in the prior art, characteristics easy and simple to handle, that the reaction times is short, aftertreatment is easy, by product is few that this synthetic method has.
The technical solution used in the present invention is as follows:
2, the synthetic method of 6-dimethyl benzene fluoroacetic acid is characterized in that, comprises the steps:
1) in the aqueous solution of alkali, add 2, the 6-xylenol, 2,6-xylenol and alkali add by 0.5～1.0: 1.0 mol ratio;
2) after the mixture stirring and dissolving, fully react after-filtration, filtrate heats up and removes moisture, gets 2,6-dimethyl benzene phenates;
3) with 2,6-dimethyl benzene phenates and Mono Chloro Acetic Acid be 0.5～1.0: 1.0 mixing in molar ratio, are heated to 2, and the complete fusion of 6-dimethyl benzene phenates and Mono Chloro Acetic Acid reacts in atmosphere of inert gases;
4) reaction finish after, be cooled to room temperature, add water or alkali liquid washing, filter crude product;
5) crude product obtains 2 through recrystallization, the pure product of 6-dimethyl benzene fluoroacetic acid.
Reaction formula is as follows:
In the preferred embodiment of the present invention, described alkali is sodium hydroxide or potassium hydroxide, 2, and 6-xylenol and alkali add by 0.6～0.8: 1.0 mol ratio.
In the preferred embodiment of the present invention, 2,6-xylenol sodium and chloroacetic substitution reaction are carried out under 130 ℃～150 ℃ temperature, are higher than 2, molten some temperature of 6-dimethyl benzene fluoroacetic acid.
In the preferred embodiment of the present invention, 2,6-xylenol sodium and chloroacetic substitution reaction are preferably carried out under 140 ℃～145 ℃ temperature, to obtain the optimum response effect.
In the preferred embodiment of the present invention, 2, the reaction times of 6-dimethyl benzene phenates and Mono Chloro Acetic Acid generation substitution reaction is preferably 1.5 hours～and 2 hours.
In the preferred embodiment of the present invention, 2, the recrystallization of 6-dimethyl benzene fluoroacetic acid crude product can carry out in ethanol-water solution.
The present invention is by adding 2 in the aqueous solution of alkali, the reaction of 6-xylenol generates salt, then with the water evaporate to dryness, use 2 again, 6-dimethyl benzene phenates and Mono Chloro Acetic Acid carry out substitution reaction under molten state, its reaction difficulty reduces, and speed of response is accelerated, and also need not the additional Mono Chloro Acetic Acid and the sodium hydroxide of repeated multiple times in the reaction process.Compare with having the substitution reaction of in solution, carrying out now, have characteristics easy and simple to handle, that the reaction times is short, aftertreatment is easy, by product is few.
Embodiment
The present invention will be further described below in conjunction with embodiment, but do not constitute any limitation of the invention.
Embodiment 1
1, add 2 in the 250ml beaker, 6-xylenol 12.2g (0.1mol) is warming up to 40 ℃, add 25%NaOH solution 16g (0.1mol), after the stirring and dissolving, fully react after-filtration, filtrate is warming up to 110 ℃ except that anhydrating, and obtains 2,6-xylenol sodium pressed powder 12.4g.
2, get 2,6-xylenol sodium 12.4g (0.086mol) and Mono Chloro Acetic Acid 8.127g (0.086mol) join in the 250ml exsiccant there-necked flask, under nitrogen atmosphere, heat temperature raising to 150 ℃, isothermal reaction 1.5h, after reaction finishes, the question response bottle cools off a little, to wherein adding 50ml warm water, jolting, after solution is cooled to room temperature, can filter solid crude product.Crude product alcohol-water recrystallization, obtain pure 2,6-dimethyl benzene fluoroacetic acid 12.6g, molar yield 70%.
Embodiment 2
1, add 2 in the 250ml beaker, 6-xylenol 12.2g (0.1mol) adds 30%NaOH solution 18g (0.135mol), after the stirring and dissolving, fully react after-filtration, filtrate is warming up to 110 ℃ except that anhydrating, obtain 2,6-xylenol sodium pressed powder 13.0g.
2, get 2,6-xylenol sodium 13.0g (0.090mol) and Mono Chloro Acetic Acid 8.505g (0.090mol) join in the 250ml exsiccant there-necked flask, under nitrogen atmosphere, heat temperature raising to 130 ℃, isothermal reaction 1.5h, after reaction finishes, the question response bottle cools off a little, to wherein adding 50ml warm water, jolting, after solution is cooled to room temperature, can filter solid crude product.Crude product alcohol-water recrystallization, obtain pure 2,6-dimethyl benzene fluoroacetic acid 13.20g, molar yield 73.2%.
Embodiment 3
1, add 2 in the 250ml beaker, 6-xylenol 12.2g (0.1mol) adds NaOH 6.8g (0.17mol) and water 12g, after the stirring and dissolving, fully react after-filtration, filtrate is warming up to 110 ℃ except that anhydrating, obtain 2,6-xylenol sodium pressed powder 13.0g.
2, get 2,6-xylenol sodium 13.0g (0.090mol) and Mono Chloro Acetic Acid 8.505g (0.090mol) join in the 250ml exsiccant there-necked flask, under nitrogen atmosphere, heat temperature raising to 140 ℃, isothermal reaction 2h, after reaction finishes, the question response bottle cools off a little, to wherein adding 30%NaOH solution 50ml, jolting, after solution is cooled to room temperature, can filter solid crude product.Crude product alcohol-water recrystallization, obtain pure 2,6-dimethyl benzene fluoroacetic acid 13.48g, molar yield 74.8%.
Embodiment 4
1, add 2 in the 250ml beaker, 6-xylenol 12.2g (0.1mol) adds NaOH 7.2g (0.18mol) and water 12g, after the stirring and dissolving, fully react after-filtration, filtrate is warming up to 110 ℃ except that anhydrating, obtain 2,6-xylenol sodium pressed powder 13.0g.
2, get 2,6-xylenol sodium 13.0g (0.090mol) and Mono Chloro Acetic Acid 10.206g (0.108mol) join in the 250ml exsiccant there-necked flask, under nitrogen atmosphere, heat temperature raising to 145 ℃, isothermal reaction 2h, after reaction finishes, the question response bottle cools off a little, to wherein adding 30%NaOH solution 50ml, jolting, after solution is cooled to room temperature, can filter solid crude product.Crude product alcohol-water recrystallization, obtain pure 2,6-dimethyl benzene fluoroacetic acid 14.36g, molar yield 79.7%.
Embodiment 5
1, add 2 in the 250ml beaker, 6-xylenol 12.2g (0.1mol) adds NaOH 8g (0.2mol) and water 12g, after the stirring and dissolving, fully react after-filtration, filtrate is warming up to 110 ℃ except that anhydrating, obtain 2,6-xylenol sodium pressed powder 13.0g.
2, get 2,6-xylenol sodium 13.0g (0.090mol) and Mono Chloro Acetic Acid 10.2g (0.108mol) join in the 250ml exsiccant there-necked flask, under nitrogen atmosphere, heat temperature raising to 145 ℃, isothermal reaction 2h, after reaction finishes, the question response bottle cools off a little, to wherein adding 30%NaOH solution 50ml, jolting, after solution is cooled to room temperature, can filter solid crude product.Crude product alcohol-water recrystallization, obtain pure 2,6-dimethyl benzene fluoroacetic acid 15.50g, molar yield 86.0%.
The foregoing description is a preferred implementation of the present invention; but embodiments of the present invention are not restricted to the described embodiments; other any do not deviate from change, the modification done under spirit of the present invention and the principle, substitutes, combination, simplify; all should be the substitute mode of equivalence, be included within protection scope of the present invention.
Claims (6)
1.2 the synthetic method of 6-dimethyl benzene fluoroacetic acid is characterized in that, comprises the steps:
1) in the aqueous solution of alkali, add 2, the 6-xylenol, 2,6-xylenol and alkali add by 0.5～1.0: 1.0 mol ratio;
2) mixture stirring and dissolving is fully reacted after-filtration, and filtrate heats up and removes moisture, gets 2,6-dimethyl benzene phenates;
3) with 2,6-dimethyl benzene phenates and Mono Chloro Acetic Acid be 0.5～1.0: 1.0 mixing in molar ratio, are heated to 2, and the complete fusion of 6-dimethyl benzene phenates and Mono Chloro Acetic Acid reacts in atmosphere of inert gases;
4) reaction finish after, be cooled to room temperature, add water or alkali liquid washing, filter crude product;
5) crude product obtains 2 through recrystallization, the pure product of 6-dimethyl benzene fluoroacetic acid.
2. according to 2 described in the claim 1, the synthetic method of 6-dimethyl benzene fluoroacetic acid is characterized in that: described alkali is sodium hydroxide or potassium hydroxide, 2, and 6-xylenol and alkali add by 0.6～0.8: 1.0 mol ratio.
3. according to 2 described in the claim 2, the synthetic method of 6-dimethyl benzene fluoroacetic acid is characterized in that: 2, and 6-xylenol sodium and chloroacetic substitution reaction are carried out under 130 ℃～150 ℃ temperature.
4. according to 2 described in the claim 3, the synthetic method of 6-dimethyl benzene fluoroacetic acid is characterized in that: 2, and 6-xylenol sodium and chloroacetic substitution reaction are preferably carried out under 140 ℃～145 ℃ temperature.
5. according to 2 described in claim 3 or 4, the synthetic method of 6-dimethyl benzene fluoroacetic acid is characterized in that: 2, and the reaction times of 6-dimethyl benzene phenates and Mono Chloro Acetic Acid generation substitution reaction is preferably 1.5 hours～and 2 hours.
6. according to 2 described in the claim 5, the synthetic method of 6-dimethyl benzene fluoroacetic acid is characterized in that: 2, and the recrystallization of 6-dimethyl benzene fluoroacetic acid crude product carries out in ethanol-water solution.
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Cited By (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103159610A (en) * | 2013-04-10 | 2013-06-19 | 山东潍坊润丰化工有限公司 | Method for synthesizing phenoxy carboxylate herbicide original medicine |
| CN103351296A (en) * | 2013-07-23 | 2013-10-16 | 山东科源化工有限公司 | Preparation method of high-purity 2,4-D |
| CN106083564A (en) * | 2016-07-28 | 2016-11-09 | 厦门市蔚嘉化学科技有限公司 | The synthesis of a kind of 2,6 dimethyl phenoxyacetic acids and purification process |
| CN106167453A (en) * | 2016-08-04 | 2016-11-30 | 山东省化工研究院 | A kind of preparation method of 2,4 dichlorphenoxyacetic acid methyl ester |
| CN106242971A (en) * | 2016-08-04 | 2016-12-21 | 山东省化工研究院 | A kind of chloracetate synthesis in water technology and the new method of preparation 2,4 D esters thereof |
| CN106278862A (en) * | 2016-08-04 | 2017-01-04 | 山东省化工研究院 | A kind of new technique for synthesizing of 2,4 dichlorphenoxyacetic acids |
| CN108424361A (en) * | 2017-02-13 | 2018-08-21 | 山东润博生物科技有限公司 | A kind of preparation method of 2,4 dichlorophenoxyacetic acid |
| CN108503538A (en) * | 2017-02-28 | 2018-09-07 | 山东润博生物科技有限公司 | The preparation method of one kind 2,4- dichlorphenoxyacetic acids |
| CN108530284A (en) * | 2018-04-08 | 2018-09-14 | 湘潭大学 | The preparation method of o-methyl-benzene fluoroacetic acid |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPH01113336A (en) * | 1987-10-26 | 1989-05-02 | Mitsubishi Petrochem Co Ltd | Production of alkylphenoxyacetic acid |
| CN1208405A (en) * | 1995-12-13 | 1999-02-17 | 艾博特公司 | Retroviral protease inhibiting compounds |
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2010
- 2010-07-02 CN CN2010102163289A patent/CN101967092A/en active Pending
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPH01113336A (en) * | 1987-10-26 | 1989-05-02 | Mitsubishi Petrochem Co Ltd | Production of alkylphenoxyacetic acid |
| CN1208405A (en) * | 1995-12-13 | 1999-02-17 | 艾博特公司 | Retroviral protease inhibiting compounds |
Cited By (11)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103159610A (en) * | 2013-04-10 | 2013-06-19 | 山东潍坊润丰化工有限公司 | Method for synthesizing phenoxy carboxylate herbicide original medicine |
| CN103351296A (en) * | 2013-07-23 | 2013-10-16 | 山东科源化工有限公司 | Preparation method of high-purity 2,4-D |
| CN106083564A (en) * | 2016-07-28 | 2016-11-09 | 厦门市蔚嘉化学科技有限公司 | The synthesis of a kind of 2,6 dimethyl phenoxyacetic acids and purification process |
| CN106083564B (en) * | 2016-07-28 | 2019-02-15 | 厦门市蔚嘉化学科技有限公司 | A kind of synthesis of 2,6- dimethyl phenoxyacetic acid and purification process |
| CN106167453A (en) * | 2016-08-04 | 2016-11-30 | 山东省化工研究院 | A kind of preparation method of 2,4 dichlorphenoxyacetic acid methyl ester |
| CN106242971A (en) * | 2016-08-04 | 2016-12-21 | 山东省化工研究院 | A kind of chloracetate synthesis in water technology and the new method of preparation 2,4 D esters thereof |
| CN106278862A (en) * | 2016-08-04 | 2017-01-04 | 山东省化工研究院 | A kind of new technique for synthesizing of 2,4 dichlorphenoxyacetic acids |
| CN106167453B (en) * | 2016-08-04 | 2019-06-21 | 山东省化工研究院 | A kind of preparation method of 2,4 dichlorophenoxyacetic acid methyl esters |
| CN108424361A (en) * | 2017-02-13 | 2018-08-21 | 山东润博生物科技有限公司 | A kind of preparation method of 2,4 dichlorophenoxyacetic acid |
| CN108503538A (en) * | 2017-02-28 | 2018-09-07 | 山东润博生物科技有限公司 | The preparation method of one kind 2,4- dichlorphenoxyacetic acids |
| CN108530284A (en) * | 2018-04-08 | 2018-09-14 | 湘潭大学 | The preparation method of o-methyl-benzene fluoroacetic acid |
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Application publication date: 20110209 |