WO2012024920A1 - Procédé pour la préparation de 5-amino-3-cyano-1-(2,6-dichloro-4-trifluorométhylphényl)-4-trifluorométhylsulfinylpyrazole - Google Patents

Procédé pour la préparation de 5-amino-3-cyano-1-(2,6-dichloro-4-trifluorométhylphényl)-4-trifluorométhylsulfinylpyrazole Download PDF

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Publication number
WO2012024920A1
WO2012024920A1 PCT/CN2011/071577 CN2011071577W WO2012024920A1 WO 2012024920 A1 WO2012024920 A1 WO 2012024920A1 CN 2011071577 W CN2011071577 W CN 2011071577W WO 2012024920 A1 WO2012024920 A1 WO 2012024920A1
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acidic medium
acid
solid
reaction
dichloro
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English (en)
Chinese (zh)
Inventor
赵永长
于慧梅
宋蕾
朱笑坤
陈建伟
王文军
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NUTRICHEM INTERNATIONAL CO Ltd
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NUTRICHEM INTERNATIONAL CO Ltd
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D231/00—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings
    • C07D231/02—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings
    • C07D231/10—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
    • C07D231/14—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members 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
    • C07D231/44—Oxygen and nitrogen or sulfur and nitrogen atoms

Definitions

  • the present invention relates to a process for the preparation of 5-amino-3-cyano-1-(2,6-dichloro-4-trifluoromethylphenyl)-4-trifluoromethylsulfinylpyrazole. Background technique
  • fipronil The structure of fipronil is novel and its mechanism of action is unique. Its mechanism is mainly to control the metabolism of chloride by ⁇ -aminobutyric acid (GABA) receptor. It has contact, stomach poisoning and moderate systemic action. It is on lepidoptera and flies. A series of pests such as the genus Coleoptera have high insecticidal activity. Moreover, it has many advantages such as no cross-resistance and safety of use with existing insecticides.
  • GABA ⁇ -aminobutyric acid
  • the agent can be applied to the soil or foliar spray: Applying to the soil can effectively control the corn root beetle, golden worm and the ground tiger; when the leaf is sprayed, it has high levels of the diamondback moth, the cabbage butterfly, the rice glutinous horse, etc. It is effective and has a long-lasting effect.
  • 5-amino-3-cyano-1-(2,6-dichloro-4-trifluoromethylphenyl)-4-trifluoromethylthiopyrazole is an important intermediate for the preparation of fipronil, After the trifluoromethylthio group of the intermediate is oxidized to a trifluoromethylsulfinyl group, fipronil is obtained.
  • the object of the present invention is to overcome the shortcomings of the prior art solvent recovery, and to provide a solvent-recoverable preparation of 5-amino-3-cyano-1-(2,6-dichloro-4-trifluoromethylphenyl). a method of 4-trifluoromethylsulfinylpyrazole.
  • CN1332730A proposes to recover trifluoroacetic acid by adding chlorobenzene and distilling off trifluoroacetic acid, it is inevitable to introduce a large amount of water into the reaction system by using hydrogen peroxide as an oxidizing agent. Acetic acid and water easily form an azeotropic mixture, so that the recovered trifluoroacetic acid is contained There is a large amount of water, plus trifluoroacetic acid and water miscible, the recovered trifluoroacetic acid has a water content of more than 8%.
  • the invention provides a preparation method of 5-amino-3-cyano-1-(2,6-dichloro-4-trifluoromethylphenyl)-4-trifluoromethylsulfinylpyrazole,
  • the 5-amino-3-cyano-1-(2,6-dichloro-4-trifluoromethylphenyl)-4-trifluoromethylsulfinylpyrazole has the formula ( ⁇ ) shown below Structure:
  • the preparation method of the 5-amino-3-cyano-1-(2,6-dichloro-4-trifluoromethylphenyl)-4-trifluoromethylsulfinylpyrazole comprises an acidic medium
  • the solid oxidant is represented by the formula (I)
  • the invention adopts a solid oxidant instead of hydrogen peroxide as an oxidant, reduces the water content in the recovered acidic medium (such as trifluoroacetic acid), realizes the recycling of an acidic medium (such as trifluoroacetic acid), and is suitable for industrial production. Further, the method of the present invention has the advantages of mild reaction conditions and high safety by using a solid oxidizing agent instead of hydrogen peroxide as an oxidizing agent. Detailed ways
  • the compound represented by the following formula (I) is contacted with a solid oxidizing agent in the presence of an acidic medium, and the reaction medium is recovered to obtain a compound represented by the formula ( ⁇ ).
  • the reaction process is as follows:
  • the molar ratio of the compound of the formula (I) to the solid oxidizing agent may be 1: 0.9-6.0, preferably 1 : 1-3, more preferably 1: 1.2 - 1.7, still more preferably 1: 1.3 - 1.5.
  • the solid oxidizing agent may be various oxidizing agents capable of oxidizing a trifluoromethylthio group to a trifluoromethylsulfinyl group at room temperature, preferably including sodium perborate, potassium peroxymonosulfate or sodium percarbonate. And one or more of calcium peroxide and magnesium peroxide, further preferably potassium peroxymonosulfate and/or sodium perborate, wherein the sodium perborate may be hydrated sodium perborate having 1 or 4 crystal waters. .
  • the acidic medium may be a liquid acidic medium and may be selected from one or more of the organic carboxylic acids having the following structural formula:
  • R is halogen or hydrogen
  • R, X, and Y may be the same or different.
  • the halogen may be fluorine, chlorine, bromine or iodine, preferably fluorine.
  • the acidic medium may be one or more of trifluoroacetic acid, difluoroacetic acid, dichloroacetic acid, monofluorodichloroacetic acid and difluoromonochloroacetic acid, further preferably trifluoroacetic acid, difluoroacetic acid One or more of acetic acid and difluoromonochloroacetic acid.
  • the present inventors have found that while using at least one of R, X and Y as an acidic medium of fluorine, hydrated sodium perborate having one or four crystal waters is used as a solid oxidant, and the recovery is lowered.
  • the water content of the acidic medium also reduces the corrosion of the glass container. This may be due to the presence of by-product sodium borate or, possibly, due to the lower water content in the reaction system, which inhibits the production of small amounts of hydrofluoric acid by-products from the fluorine-containing acidic medium, thereby reducing corrosion of the glass container.
  • the acidic medium be an acidic medium in which at least one of R, X and Y is fluorine, and the solid oxidant is hydrated sodium perborate.
  • the inventors have also found that when dichloroacetic acid is used as an acidic medium, compared with the use of a fluorine-containing acidic medium, Reduces corrosion of the glass container.
  • the reason may be that a small amount of hydrofluoric acid by-product produced by a fluorine-containing acidic medium corrodes the glass container, and the use of dichloroacetic acid does not cause corrosion of the glass container due to the absence of the above-mentioned hydrofluoric acid by-product.
  • the use of dichloroacetic acid in combination with various solid oxidants does not present the problem of corrosion of the glass container. Therefore, in the present invention, it is also preferred that the acidic medium is dichloroacetic acid.
  • an aqueous solution of sulfuric acid when used as an acidic medium, it also has better selectivity and yield, and, compared to trifluoroacetic acid, difluoroacetic acid, dichloroacetic acid, monofluorodichloroacetic acid, difluoroacetic acid.
  • An acidic medium such as monochloroacetic acid, which is much easier to obtain in an aqueous solution of sulfuric acid and which is relatively inexpensive, is more suitable for industrial production. Therefore, the acidic medium may also be an aqueous sulfuric acid solution, and the aqueous sulfuric acid solution may have a concentration of 70 to 90% by weight, preferably 80 to 88% by weight.
  • the weight ratio of the compound of the formula (I) to the acidic medium may be from 1:2 to 10, preferably from 1:3 to 8, more preferably from 1:3.5 to 5.
  • the oxidation reaction condition of the compound represented by the formula (I) and the solid oxidizing agent may be carried out by adding the compound of the formula (I) to an acidic medium at -10 ° C to 50 ° C until it is sufficiently dissolved.
  • the solid oxidizing agent is added, and the reaction temperature may be -10 ° C to 50 ° C, preferably 5 to 20 ° C, and more preferably 8 to 12 ° C.
  • the reaction time may be from 1 to 48 hours, preferably from 4 to 6 hours.
  • the oxidizing agent is added in portions, which is more favorable for improving the selectivity of the reaction.
  • the solid oxidizing agent may be added in 3 to 6 portions, wherein the first time is added to the solid oxidizing agent equimolar to the compound represented by the formula (I), and the remaining amount of the solid oxidizing agent may be equally divided into 2 to 5 parts.
  • the mixture obtained by contacting the solid oxidizing agent with the compound of the formula (I) may be contacted with a reducing agent to remove excess oxidizing agent.
  • the reducing agent may be one or more of insurance powder, sodium sulfite, sulfur dioxide and other reducing agents, preferably insurance powder and/or sodium sulfite.
  • the reducing agent is added in such a manner that the amount of the reducing agent is added so as to be able to remove the excess oxidizing agent.
  • a reducing agent may be added so that the mixture just does not allow the starch potassium iodide test paper to change color.
  • the acidic medium when the acidic medium is an organic carboxylic acid represented by the above structural formula, the acidic medium can be distilled off under reduced pressure after removing an excessive amount of the oxidizing agent.
  • the reaction liquid after removing excess oxidant may be diluted with water at a temperature of -5 ° C to 5 ° C, and then filtered to obtain a solid.
  • the product wherein the weight ratio of the amount of water used for dilution to the aqueous solution of sulfuric acid is 1-3:1.
  • the method provided by the present invention may further comprise recrystallizing the product after distilling off the acidic medium under reduced pressure.
  • the solvent used for the recrystallization may be one or more of toluene, chlorobenzene, ethyl acetate, and an alcohol having 1 to 4 carbon atoms.
  • the method of recrystallization may be: firstly purifying the solid product of the acidic medium under water pressure to remove residual acid and inorganic salt, and then dissolving the solid product by heating with a solvent until the solid is completely dissolved, and slowly cooling the clear solution. Recrystallization from 0 to 5 ° C, then at 0-5 ° C for 2 hours, filtering to obtain crystal Body product.
  • the amount of water for washing may be 0.8 to 3 parts by weight
  • the amount of solvent used for recrystallization may be 0.2 to 2 parts by weight, based on 1 part by weight of the product obtained by distilling off the acidic medium under reduced pressure.
  • the present invention is more advantageous in the recovery of trifluoroacetic acid than the hydrogen peroxide and trifluoroacetic acid systems because of the large amount of water present in the system due to oxidation using a solid oxidizing agent.
  • the solid obtained by filtration was heated to 300 g of chlorobenzene to completely dissolve, and then slowly cooled at 0-5 ° C, and then kept for 2 hours, filtered and dried to obtain 122 g of a white solid, which was detected by GC.
  • the main component of the white solid is 5-amino-3-cyano- 1-(2,6-Dichloro-4-trifluoromethylphenyl)-4-trifluoromethylsulfinylpyrazole having a purity of 95% and a yield of 93%.
  • the temperature of the reaction system was maintained at 10-12 ° C, and 49.9 g (concentration: 30%, 0.44 mol) H 2 0 2 was slowly added dropwise, time control At 2h; keep the temperature at 10-12 ° C for 5h, GC to monitor the completion of the reaction, until the conversion of raw materials is greater than 98%; add 350g of chlorobenzene, azeotropic distillation under reduced pressure to recover a mixture of trifluoroacetic acid, chlorobenzene and water 440 g of trifluoroacetic acid having a water content of 8.5% was obtained by liquid separation. After the azeotropic distillation under reduced pressure, the chlorobenzene was distilled under reduced pressure until no fraction was obtained.
  • the reaction was further incubated for 3 hours, and the degree of reaction was monitored by GC until the conversion of the raw material was more than 98%, and sodium sulfite was added in portions. In order to remove the oxide, (0.1g per batch), the reaction was terminated. The total amount of sodium sulfite added was such that the reaction system could not change the color of the starch potassium iodide test paper, and the mixture was stirred for 5 minutes, and trifluoroacetic acid was distilled under reduced pressure to obtain water content.
  • the reaction was further incubated for 3 h, and the degree of completion of the reaction was monitored by GC until the conversion of the raw material was more than 99%, and sodium sulfite was added in portions to remove the oxide (0.1 g per batch) to terminate the reaction.
  • the degree of completion of the reaction was monitored by GC until the conversion of the raw material was greater than 98%, and sodium sulfite was added in portions to remove the oxide (0.1 g per batch). To terminate the reaction. Control the batch or total amount of sodium sulfite added, so that the reaction system can not just change the color of the starch potassium iodide test paper, stir for 5 minutes, dichloroacetic acid is distilled off under reduced pressure to obtain 420 g of anhydrous dichloroacetic acid.
  • the degree of completion of the reaction was monitored by GC until the conversion of the raw material was greater than 98%, and sodium sulfite was added in portions to remove oxides (0.1 g per batch). To terminate the reaction. Control the batch or total amount of sodium sulfite added so that the reaction system just does not change the color of the starch potassium iodide test paper, stir for 5 minutes, and recover by distillation under reduced pressure to obtain a water content of less than 2% by weight of trifluoroacetic acid.
  • the white solid was mainly 5-amino-3-cyano-1-(2,6-dichloro-4-trifluoromethylphenyl)-4-trifluoro Methylsulfinylpyrazole, purity 96%, yield 89.2%.
  • the above experiment was repeated 10 times using the above 1000 ml reaction flask, and it was found that the bottom of the reaction bottle contacting the reaction solution was no longer transparent and the edges were blurred, indicating that the reaction system had a certain glass. Corrosion effect.
  • the degree of completion of the reaction was monitored by GC until the conversion of the raw material was greater than 98%, and the SO 2 gas was introduced to remove the oxide to terminate the reaction. Control the total amount of S0 2 gas inflow, so that the reaction system just can not make the starch potassium iodide test paper discoloration, stir for 5 minutes, put the reaction bottle in an ice water bath, add 1800g water to the reaction droplet, at the reaction liquid temperature After being reduced to 0 °, it was filtered to give a white solid, 110 g, which was determined by GC.
  • the main component of the white solid was 5-amino-3-cyano-1-(2,6-dichloro-4-trifluoromethylphenyl) -4-trifluoromethylsulfinylpyrazole, purity 91%, yield 84%.

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  • Organic Chemistry (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)

Abstract

L'invention porte sur un procédé pour la préparation de 5-amino-3-cyano-1-(2,6-dichloro-4-trifluorométhylphényl)-4-trifluorométhylsulfinylpyrazole (Fipronil) (II). Ce procédé comprend l'oxydation de 5-amino-3-cyano-1-(2,6-dichloro-4-trifluorométhylphényl)-4-trifluorométhylthiopyrazole (formule (I)), utilisé comme matière par un oxydant solide dans un milieu acide, la récupération du milieu réactionnel et l'obtention de Fipronil.
PCT/CN2011/071577 2010-08-25 2011-03-07 Procédé pour la préparation de 5-amino-3-cyano-1-(2,6-dichloro-4-trifluorométhylphényl)-4-trifluorométhylsulfinylpyrazole Ceased WO2012024920A1 (fr)

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CN201010263034.1 2010-08-25
CN 201010263034 CN101955460B (zh) 2010-08-25 2010-08-25 一种制备5-氨基-3-氰基-1-（2,6-二氯-4-三氟甲基苯基）-4-三氟甲基亚磺酰基吡唑的方法

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CN101955460B (zh) * 2010-08-25 2012-12-12 北京颖泰嘉和生物科技有限公司 一种制备5-氨基-3-氰基-1-（2,6-二氯-4-三氟甲基苯基）-4-三氟甲基亚磺酰基吡唑的方法
BRPI1104747B1 (pt) * 2011-09-14 2017-11-28 Rotam Agrochem International Company Limited Process for the preparation of n-substituted pyrazole compounds
CN114213330A (zh) * 2021-12-29 2022-03-22 天和药业股份有限公司 一种氟虫腈精制母液的处理方法
CN115594635A (zh) * 2022-09-29 2023-01-13 浙江美诺华药物化学有限公司（Cn） 一种去氯氟虫腈的合成方法

Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN101250158A (zh) * 2008-04-02 2008-08-27 湖南化工研究院 一种氟虫腈的制备方法
WO2009077853A1 (fr) * 2007-12-19 2009-06-25 Vétoquinol Procédé de préparation du fipronil et de ses analogues
CN101544607A (zh) * 2009-04-30 2009-09-30 宁波中化化学品有限公司 一种含三氟甲基亚磺酰基的1-芳基吡唑化合物的合成方法
CN101955460A (zh) * 2010-08-25 2011-01-26 北京颖新泰康国际贸易有限公司 一种制备5-氨基-3-氰基-1-（2,6-二氯-4-三氟甲基苯基）-4-三氟甲基亚磺酰基吡唑的方法

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2009077853A1 (fr) * 2007-12-19 2009-06-25 Vétoquinol Procédé de préparation du fipronil et de ses analogues
CN101250158A (zh) * 2008-04-02 2008-08-27 湖南化工研究院 一种氟虫腈的制备方法
CN101544607A (zh) * 2009-04-30 2009-09-30 宁波中化化学品有限公司 一种含三氟甲基亚磺酰基的1-芳基吡唑化合物的合成方法
CN101955460A (zh) * 2010-08-25 2011-01-26 北京颖新泰康国际贸易有限公司 一种制备5-氨基-3-氰基-1-（2,6-二氯-4-三氟甲基苯基）-4-三氟甲基亚磺酰基吡唑的方法

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