CN110240545B - Preparation method of 2- (5-fluoro-2, 4-dinitrophenoxy) acetic acid - Google Patents
Preparation method of 2- (5-fluoro-2, 4-dinitrophenoxy) acetic acid Download PDFInfo
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- CN110240545B CN110240545B CN201810191113.2A CN201810191113A CN110240545B CN 110240545 B CN110240545 B CN 110240545B CN 201810191113 A CN201810191113 A CN 201810191113A CN 110240545 B CN110240545 B CN 110240545B
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- C07—ORGANIC CHEMISTRY
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- C07C201/00—Preparation of esters of nitric or nitrous acid or of compounds containing nitro or nitroso groups bound to a carbon skeleton
- C07C201/06—Preparation of nitro compounds
- C07C201/12—Preparation of nitro compounds by reactions not involving the formation of nitro groups
Abstract
The invention discloses a preparation method of 2- (5-fluoro-2, 4-dinitrophenoxy) acetic acid. The preparation method comprises the following steps: 1, 5-difluoro-2, 4-dinitrobenzene and ethylene glycol are used as raw materials and react under the action of alkali to obtain 2- (5-fluoro-2, 4-dinitrophenoxy) ethanol, and the 2- (5-fluoro-2, 4-dinitrophenoxy) ethanol is oxidized under the action of an oxidant to obtain the 2- (5-fluoro-2, 4-dinitrophenoxy) acetic acid. The preparation method has the advantages of simple process operation, short reaction time, no need of high temperature, high product purity, high yield, green and environment-friendly whole process and less three wastes.
Description
Technical Field
The invention relates to the field of preparation of pesticide raw materials, and particularly relates to a preparation method of 2- (5-fluoro-2, 4-dinitrophenoxy) acetic acid.
Background
2- (5-fluoro-2, 4-dinitrophenoxy) acetic acid is an important pesticide intermediate and is used for preparing N-phenylphthalimide herbicide flumioxazin. 2- (5-fluoro-2, 4-dinitrophenoxy) acetic acid and ester thereof are hydrogenated under the catalysis of palladium/carbon or platinum/carbon to obtain 6-amino-7-fluoro-1, 4-benzoxazine-3 (4H) -ketone (US4803270, Bioscience Biotechnology and Biochemistry,1994,58(4),788-789), and 6-amino-7-fluoro-4-propynyl-1, 4-benzoxazine-3 (4H) -ketone is reacted with 3,4,5, 6-tetrahydrophthalic anhydride to prepare flumioxazin (US5108488, US 4640707).
At present, the literature reports methods for preparing 2- (5-fluoro-2, 4-dinitrophenoxy) acetic acid mainly include a 3-fluorophenol method, a 2, 4-difluoronitrobenzene method and a 1, 5-difluoro-2, 4-dinitrobenzene method.
3-fluorophenol method: 3-fluorophenol reacts with chloroacetic acid to obtain 2-fluorophenoxyacetic acid, and then 2- (5-fluoro-2, 4-dinitrophenoxy) acetic acid is obtained through nitration reaction (US4803270, Bioscience Biotechnology and Biochemistry,1994,58(4),788-789, J.Am.chem.Soc,1959,81(1), 94-101).
The raw material 3-fluorophenol used by the method is high in price and not easy to obtain; the yield of the two steps of reaction is low, so that the total yield of the product is greatly reduced; in addition, ether bonds are easy to break in the nitration process, and the nitration selectivity is not high.
2, 4-difluoronitrobenzene method: firstly, 2, 4-difluoronitrobenzene is subjected to nitration reaction to obtain 1, 5-difluoro-2, 4-dinitrobenzene, and then the 1, 5-difluoro-2, 4-dinitrobenzene reacts with glycolic acid in the presence of alkali to obtain 2- (5-fluoro-2, 4-dinitrophenoxy) acetic acid (CN101948389A)
The yield of the method is 28-81%, because water and glycolic acid can perform a competitive reaction, water needs to be strictly controlled in the reaction process, and the glycolic acid serving as a raw material is expensive and high in production cost.
1, 5-difluoro-2, 4-dinitrobenzene process: 1, 5-difluoro-2, 4-dinitrobenzene and dicyclohexylammonium glycolate are reacted in the presence of an organic solvent and alkali to obtain 2- (5-fluoro-2, 4-dinitrophenoxy) acetic acid (CN 104130128A).
Although the method has a short route, the preparation process of the dicyclohexylammonium glycolate which is used as the raw material needs to use high-price glycolic acid, so that the production cost is high, and the method is not beneficial to commercial production.
Disclosure of Invention
Aiming at the defects in the prior art, the invention provides the method for preparing the 2- (5-fluoro-2, 4-dinitrophenoxy) acetic acid, which has the advantages of high yield, environmental protection, less three wastes and low cost.
A preparation method of 2- (5-fluoro-2, 4-dinitrophenoxy) acetic acid (III) takes 1, 5-difluoro-2, 4-dinitrobenzene (II) and ethylene glycol as raw materials, under the action of alkali, 2- (5-fluoro-2, 4-dinitrophenoxy) ethanol (I) is obtained by reaction, 2- (5-fluoro-2, 4-dinitrophenoxy) ethanol (I) is oxidized by an oxidant to obtain 2- (5-fluoro-2, 4-dinitrophenoxy) acetic acid (III), and the reaction formula is expressed as follows:
the alkali is inorganic alkali or organic alkali; preferably, the inorganic base is sodium hydroxide, potassium hydroxide, anhydrous sodium carbonate or anhydrous potassium carbonate; the organic base is triethylamine or pyridine.
The mass ratio of the 1, 5-difluoro-2, 4-dinitrobenzene to the ethylene glycol is 1: 1-5, and the molar ratio of the alkali to the 1, 5-difluoro-2, 4-dinitrobenzene is 0.5-1.5: 1.
The oxidant is one or more of air, oxygen, hydrogen peroxide or sodium hypochlorite, and the molar ratio of the oxidant to the compound (I) is 1-3: 1. The oxidizing agent is further preferably air or oxygen.
The oxidation reaction is added with a catalyst, the preferable catalyst is a mixture of tetramethyl piperidinyloxy (TEMPO), ferric nitrate nonahydrate and an alkali metal halide such as potassium chloride or potassium bromide, and the molar ratio of the tetramethyl piperidinyloxy, the ferric nitrate nonahydrate and the alkali metal halide to the compound (I) is 1:1:1: 10-100.
Compared with the prior art, the invention has the following remarkable technical effects:
1, 5-difluoro-2, 4-dinitrobenzene and ethylene glycol directly react, a catalyst is not needed, the reaction time is short, and the post-treatment is simple;
2. when the oxidation reaction is carried out, no other toxic by-products are generated, and the method is green and environment-friendly;
3. the product 2- (5-fluoro-2, 4-dinitrophenoxy) acetic acid has high purity and yield;
4. the method has the advantages of simple process operation, short reaction time, no need of high temperature, high product purity and yield, green and environment-friendly whole process, less three wastes and suitability for industrial production.
Detailed Description
The following examples are further detailed descriptions of the present invention, but do not limit the scope of the present invention.
Example 1
6.12g of 1, 5-difluoro-2, 4-dinitrobenzene, 15mL of ethylene glycol and 3.03g of triethylamine were charged into the reactor and reacted at room temperature for 2.5 hours. After the reaction is finished, adding 20ml of water, extracting with 50ml of toluene, washing the organic layer with 20ml of water once, collecting the organic phase, and desolventizing to obtain 2- (5-fluoro-2, 4-dinitrophenoxy) ethanol with the yield of 84%;1H NMR(500MHz,CDCl3)δ8.81(d,J＝7.8Hz,1H),7.04(d,J＝11.9Hz,1H),4.44–4.29(m,2H),4.08(dt,J＝5.8,4.6Hz,2H),2.40(t,J＝6.3Hz,1H)。
example 2
10.2g of 1, 5-difluoro-2, 4-dinitrobenzene, 14mL of ethylene glycol and 4.24g of anhydrous sodium carbonate were charged into a reactor and reacted at room temperature for 3 hours. After the reaction, 30ml of water is added, 55ml of toluene is used for extraction, the organic layer is washed once by 20ml of water, and 2- (5-fluoro-2, 4-dinitrophenoxy) ethanol is obtained after the organic phase is collected and desolventized, wherein the yield is 86%.
Example 3
12.2g of 1, 5-difluoro-2, 4-dinitrobenzene, 23mL of ethylene glycol and 5.05g of triethylamine were charged into a reactor and reacted at room temperature for 2 hours. After the reaction, 35ml of water is added, 55ml of toluene is used for extraction, the organic layer is washed once by 30ml of water, the organic phase is collected and desolventized to obtain the 2- (5-fluoro-2, 4-dinitrophenoxy) ethanol, and the yield is 85 percent.
Example 4
8.16g of 1, 5-difluoro-2, 4-dinitrobenzene, 26mL of ethylene glycol and 2.4g of sodium hydroxide were charged into a reactor and reacted at room temperature for 2 hours. After the reaction, 40ml of water is added, 60ml of toluene is used for extraction, the organic layer is washed once by 30ml of water, the organic phase is collected and desolventized to obtain the 2- (5-fluoro-2, 4-dinitrophenoxy) ethanol with the yield of 87 percent.
Example 5
4.08g of 1, 5-difluoro-2, 4-dinitrobenzene, 17mL of ethylene glycol and 1.58g of pyridine were charged into a reactor and reacted at room temperature for 3 hours. After the reaction, 20ml of water is added, 45ml of toluene is used for extraction, the organic layer is washed once by 20ml of water, and the 2- (5-fluoro-2, 4-dinitrophenoxy) ethanol is obtained after the organic phase is collected and desolventized, wherein the yield is 84%.
Example 6
Adding 14.8g of 2- (5-fluoro-2, 4-dinitrophenoxy) ethanol and 4.48g of sodium hypochlorite into a reaction bottle, heating the mixture to 50 ℃, stirring and reacting for 13 hours, washing the reaction solution with 2 x 50mL of water, concentrating an organic phase, cooling and precipitating 2- (5-fluoro-2, 4-dinitrophenoxy) acetic acid with the yield of 82%.
Example 7
Adding 12.3g of 2- (5-fluoro-2, 4-dinitrophenoxy) ethanol, 17g of 30% hydrogen peroxide and 50mL of toluene into a reaction bottle, heating the mixture to 40 ℃, stirring for reaction for 12 hours, separating liquid, concentrating an organic phase, cooling to separate out 2- (5-fluoro-2, 4-dinitrophenoxy) acetic acid with the yield of 80%.
Example 8
Adding 7.4g of 2- (5-fluoro-2, 4-dinitrophenoxy) ethanol into a reaction bottle, stirring at room temperature for 6h under the air atmosphere (0.1Mpa), indicating that the reaction is complete by TLC, washing the reaction solution with 2 x 50mL of water, concentrating an organic phase, cooling and precipitating 2- (5-fluoro-2, 4-dinitrophenoxy) acetic acid with the purity of 91 percent and the yield of 90 percent.
Example 9
9.8g of 2- (5-fluoro-2, 4-dinitrophenoxy) ethanol and 75mL of toluene are added into a reaction bottle, the mixture is stirred for 16h at room temperature under the oxygen atmosphere (0.1Mpa), TLC shows that the reaction is complete, the reaction solution is washed by 2 x 50mL of water, the organic phase is concentrated, and the 2- (5-fluoro-2, 4-dinitrophenoxy) acetic acid is separated out by cooling, wherein the purity is 92 percent, and the yield is 91.5 percent.
Example 10
10g of 2- (5-fluoro-2, 4-dinitrophenoxy) ethanol, 0.06g of TEMPO and 0.16g of Fe (NO)3)3·9H2O, 0.05g KBr was added to the reaction flask, and stirred at room temperature for 12 hours under an air atmosphere, and TLC showed completion of the reaction. The product 2- (5-fluoro-2, 4-dinitrophenoxy) acetic acid is obtained by post treatment, and the yield is 90 percent.
Example 11
10g of 2- (5-fluoro-2, 4-dinitrophenoxy) ethanol and 1.63g of Fe (NO)3)3·9H2O, 0.63g TEMPO, 0.3g KCl and 50mL 1, 2-dichloroethane were added to the reaction flask and stirred at room temperature for 8h under oxygen atmosphere, TLC showed the reaction was complete. The reaction solution was washed with 2 × 50mL of water, the organic phase was concentrated and cooled to precipitate 2- (5-fluoro-2, 4-dinitrophenoxy) acetic acid with a yield of 97%.
In summary, the above-mentioned embodiments are only preferred embodiments of the present invention, and all equivalent changes and modifications made in the claims of the present invention should be covered by the claims of the present invention.
Claims (7)
1. A preparation method of 2- (5-fluoro-2, 4-dinitrophenoxy) acetic acid (III) is characterized in that 1, 5-difluoro-2, 4-dinitrobenzene (II) and ethylene glycol are used as raw materials and react under the action of alkali to obtain 2- (5-fluoro-2, 4-dinitrophenoxy) ethanol (I), the 2- (5-fluoro-2, 4-dinitrophenoxy) ethanol (I) is oxidized by an oxidant to obtain 2- (5-fluoro-2, 4-dinitrophenoxy) acetic acid (III), and the reaction formula is represented as follows:
wherein the alkali is sodium hydroxide, potassium hydroxide, anhydrous sodium carbonate, anhydrous potassium carbonate, triethylamine or pyridine; the oxidant is one or more of air, oxygen, hydrogen peroxide and sodium hypochlorite.
2. The preparation method according to claim 1, wherein the mass ratio of the 1, 5-difluoro-2, 4-dinitrobenzene to the ethylene glycol is 1:1 to 5, and the molar ratio of the alkali to the 1, 5-difluoro-2, 4-dinitrobenzene is 0.5 to 1.5: 1.
3. The preparation method according to claim 1, wherein the molar ratio of the oxidant to the compound (I) is 1-3: 1.
4. The method of claim 1, wherein the oxidant is air or oxygen.
5. The method of claim 1, wherein a catalyst is added to the oxidation reaction.
6. The preparation method according to claim 5, wherein the catalyst is a mixture of tetramethylpiperidinyloxy, ferric nitrate nonahydrate and an alkali metal halide, and the molar ratio of the tetramethylpiperidinyloxy, ferric nitrate nonahydrate, alkali metal halide to the compound (I) is 1:1:1: 10-100.
7. The method according to claim 6, wherein the alkali metal halide is potassium chloride or potassium bromide.
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| JPH082842B2 (en) * | 1987-09-16 | 1996-01-17 | 住友化学工業株式会社 | Fluorodinitrobenzene derivative and method for producing the same |
| TWI432427B (en) * | 2006-10-23 | 2014-04-01 | Cephalon Inc | Fused bicyclic derivatives of 2,4-diaminopyrimidine as alk and c-met inhibitors |
| CN101948389A (en) * | 2010-08-16 | 2011-01-19 | 北京颖新泰康国际贸易有限公司 | Method for preparing 2-(5-fluoro-2,4-dinitrophenoxy) acetic acid and ester thereof |
| CN102002013B (en) * | 2010-08-16 | 2013-12-04 | 北京颖泰嘉和生物科技有限公司 | Preparation method of 6-amino-7-fluoro-1,4-benzoxazine-3(4H)-ketone |
| CN104130128B (en) * | 2014-07-21 | 2016-08-24 | 浙江省诸暨合力化学对外贸易有限公司 | The synthetic method of phenoxy acetic acid ester and intermediate thereof |
| CN107176899B (en) * | 2016-03-11 | 2021-04-13 | 中国科学院上海有机化学研究所 | Method for preparing acid by oxidizing alcohol or aldehyde with oxygen |
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Effective date of registration: 20230106 Address after: 750336 south of East Taisheng Road, 16th Road, Bayin OBO Industrial Park, Alashan League economic and Technological Development Zone, Inner Mongolia Autonomous Region Patentee after: INNER MONGOLIA SHIJIE CHEMICAL Co.,Ltd. Address before: 226400 Yangkou Chemical Industrial Park, Rudong County, Nantong City, Jiangsu Province Patentee before: MAX (RUDONG) CHEMICALS Co.,Ltd. |