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WO2013026391A1 - Procédé de synthèse d'azoxystrobine et intermédiaire exclusif utilisé dans sa synthèse - Google Patents

Procédé de synthèse d'azoxystrobine et intermédiaire exclusif utilisé dans sa synthèse Download PDF

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Publication number
WO2013026391A1
WO2013026391A1 PCT/CN2012/080434 CN2012080434W WO2013026391A1 WO 2013026391 A1 WO2013026391 A1 WO 2013026391A1 CN 2012080434 W CN2012080434 W CN 2012080434W WO 2013026391 A1 WO2013026391 A1 WO 2013026391A1
Authority
WO
WIPO (PCT)
Prior art keywords
reaction
hours
toluene
azoxystrobin
catalyst
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Ceased
Application number
PCT/CN2012/080434
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English (en)
Chinese (zh)
Inventor
丁永良
代小妮
蔡宗杨
邓术清
韩丹
杨莹
曹超
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Chongqing Unisplendour Chemical Co Ltd
Original Assignee
Chongqing Unisplendour Chemical Co Ltd
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Chongqing Unisplendour Chemical Co Ltd filed Critical Chongqing Unisplendour Chemical Co Ltd
Publication of WO2013026391A1 publication Critical patent/WO2013026391A1/fr
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

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Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
    • C07D239/02—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings
    • C07D239/24—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members
    • C07D239/28—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more 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, directly attached to ring carbon atoms
    • C07D239/32—One oxygen, sulfur or nitrogen atom
    • C07D239/34—One oxygen atom
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
    • C07D239/02—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings
    • C07D239/24—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members
    • C07D239/28—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more 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, directly attached to ring carbon atoms
    • C07D239/46—Two or more oxygen, sulphur or nitrogen atoms
    • C07D239/52—Two oxygen atoms

Definitions

  • the invention relates to a process for synthesizing chemical substances, in particular to synthesis
  • (E)-2-[2-(6-Chloropyridin-4-yloxy)phenyl]-3-decyloxydecyl acrylate is an important intermediate for the synthesis of azoxystrobin.
  • the existing synthesis process of (E)-2-[2-(6-chloropyrimidin-4-yloxy)phenyl]-3-methoxypropenyl acrylate is mainly as follows:
  • Step-by-step method The main reaction formula is:
  • sodium decoxide 1: 4
  • poor atomic economy excessive sodium sterol needs to be neutralized with acetic acid, not only consume a large amount of organic acid, but also produce solid waste sodium acetate;
  • the main object of the present invention is to provide a method for synthesizing (E)-2-[2-(6-chloropyrimidin-4-yloxy)phenyl]-3-indolyl decyl acrylate. Single can significantly increase the yield of the product and shorten the synthesis time.
  • the technical solution adopted by the present invention is: a synthetic (E) -2- [2-(6-chloropyrimidine-4- The method for the base oxy)phenyl] _ 3-decyloxy decyl acrylate, the steps comprising: a: the raw material 3_( ⁇ -decyloxy) fluorenylenebenzofuran-2_(3H)-one with a carbonic acid clock The mixture is stirred in a solvent of 0. 4 - 0. 6 hours;
  • reaction system is dissolved in toluene, washed with water to remove a water-soluble substance such as an inorganic salt, and then distilled to recover a solvent of toluene, and then the crude product is dissolved in butyl acetate to filter impurities, followed by liquid phase cooling and recrystallization to obtain a target product.
  • the sodium algoxide may be added to the sodium alginate solution in step a, or a solid sodium sterol and a sterol may be added.
  • the weak base added in step a (such as 4A) ensures that the ring opening reaction is always in an alkaline atmosphere, avoiding the opening of the ring-opening product to produce by-products.
  • the addition of the catalyst DABC0 allows the coupling reaction to be completed quickly, greatly reducing the reaction time. In this way, the production time can be controlled within 10 hours, and the production efficiency is greatly improved.
  • step c it is detected that the content of the coupling product in the reaction system is less than 1% as the reaction end point. At this time, the target product content can reach more than 80%, and the final product yield is above 70%. And it also saves production time to the greatest extent.
  • the reaction time was 0. 5 hours.
  • the cooling temperature is the cooling temperature of the commonly used industrial cooling equipment, which is convenient for the equipment; the preferred time is the time value that can guarantee the process index and the most economical. 5 ⁇
  • the reaction time was 1. 5 hours.
  • the heating temperature was 140 °C. The rate of reaction and conversion at this temperature have outstanding effects.
  • the main chemical reaction formula for production is:
  • Another object of the present invention is to provide a process for producing the above-mentioned synthetic (E)-2-[2-(6-chloropyrimidin-4-yloxy)phenyl]-3-indolyl decyl acrylate.
  • the azoxystrobin method allows the synthesis process of azoxystrobin to be simple, which can significantly improve the yield of the product and shorten the synthesis time.
  • the technical solution adopted is: a method for synthesizing azoxystrobin, the steps comprising: a: mixing the raw material 3_( ⁇ -mercaptooxy)-fluorenylenebenzofuran-2-(3H)-one with a carbonic acid clock in the crucible In a benzene solvent, it is cooled to 0-10 ° C, sodium decoxide is added, and the reaction is carried out for 0.4-0.6 hours;
  • step C it is detected that the content of the coupling product in the reaction system is less than 1% as the reaction end point, and then the operation of the step d is performed.
  • the amount of (E) -2- [2-(6-chloropyrimidin-4-yloxy)phenyl]-3-methoxy decyl acrylate can be more than 80%, and the synthesis of azoxystrobin The product yield is also the largest, while at the same time maximizing production time.
  • the cooling temperature is the cooling temperature of the commonly used industrial cooling equipment, which is convenient for the equipment; the preferred time is the time value that can guarantee both the process index and the most economical.
  • the reaction time is 1.5 hours.
  • the heating temperature was 140 °C. The rate of reaction and conversion at this temperature have outstanding effects.
  • the improvement of the invention lies in the improvement of the process and the control index.
  • the ratio of the raw materials, the amount of the catalyst, etc. it can be determined according to the theoretical calculation or referring to the prior art, and is not the technical improvement of the present invention, and the space is no longer saved. A detailed description.
  • the steps are:
  • the steps are:
  • the steps are:
  • the steps are:
  • step a sodium decoxide and decyl alcohol are successively added, and other preferred process conditions are combined, and the yield and product purity are unexpectedly significantly improved.
  • the steps are:
  • the steps are:
  • the steps are:
  • azoxystrobin was directly added to the system, and the azoxystrobin product was isolated and purified to obtain 52.6 g of azoxystrobin product, and the yield of azoxystrobin was 65.2%.
  • the purity of azoxystrobin was 96.9 °/ by HPLC. .
  • the steps are:
  • azoxystrobin was directly added to the system, and 59.4 g of azoxystrobin product was isolated and purified, and the yield of azoxystrobin was 67.5%. The purity of azoxystrobin was 97.9% by HPLC.

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Plural Heterocyclic Compounds (AREA)
  • Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
  • Indole Compounds (AREA)

Abstract

L'invention porte sur un procédé de synthèse d'azoxystrobine et sur un intermédiaire utilisé dans sa synthèse, comprenant les étapes consistant à : mélanger les matières de départ 3-(α-méthoxy)méthylènebenzofurane-2(3H)-cétone et carbonate de potassium dans du solvant méthylbenzène, refroidir à 0-10°C, ajouter du méthylate de sodium et faire réagir pendant 0,4-0,6 heure, ajouter du 4,6-dichloropyrimide et un catalyseur DABCO, faire réagir pendant 1-2 heures, filtrer et enlever le sel inorganique, laver le filtrat, distiller et récupérer le méthylbenzène ; ajouter un catalyseur hydrosulfate de potassium au résidu distillé de l'étape précédente et, sous pression réduite, chauffer à 132-145°C pour réaction ; après cela, ajouter directement du 2-hydroxybenzonitrile pour synthétiser l'azoxystrobine ou, après dissolution dans du méthylbenzène, laver et récupérer le solvant, puis recristalliser et filtrer pour donner l'intermédiaire acrylate de (E)-2-[2-(6-chloropyrimid-4-yloxy)phényl]-3-méthoxyméthyle.
PCT/CN2012/080434 2011-08-24 2012-08-21 Procédé de synthèse d'azoxystrobine et intermédiaire exclusif utilisé dans sa synthèse Ceased WO2013026391A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
CN201110244816.5A CN102311392B (zh) 2011-08-24 2011-08-24 嘧菌酯及其合成中专用中间体的合成方法
CN201110244816.5 2011-08-24

Publications (1)

Publication Number Publication Date
WO2013026391A1 true WO2013026391A1 (fr) 2013-02-28

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Country Link
CN (1) CN102311392B (fr)
WO (1) WO2013026391A1 (fr)

Cited By (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN104974097A (zh) * 2015-05-29 2015-10-14 重庆紫光化工股份有限公司 一种嘧菌酯的合成方法
CN105396349A (zh) * 2015-11-24 2016-03-16 重庆欣欣向荣精细化工有限公司 用于乙基香兰素的过滤装置
AU2014317729B2 (en) * 2013-09-05 2018-03-22 Nutrichem Company Limited Methods for preparing azoxystrobin and intermediate thereof
WO2019178947A1 (fr) * 2018-03-23 2019-09-26 帕潘纳(北京)科技有限公司 Procédé de préparation d'azoxystrobine et de son intermédiaire
CN114685375A (zh) * 2020-12-28 2022-07-01 北京颖泰嘉和生物科技股份有限公司 [2-(6-氯嘧啶-4-氧)苯基]-3,3-二甲氧基丙烯酸甲酯的制备方法

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CN102311392B (zh) * 2011-08-24 2014-01-22 重庆紫光化工股份有限公司 嘧菌酯及其合成中专用中间体的合成方法
CN103214423B (zh) 2013-03-20 2016-03-16 北京颖泰嘉和生物科技股份有限公司 一种丙烯酸酯类化合物的制备方法
CN103265496B (zh) * 2013-05-16 2015-02-25 北京颖泰嘉和生物科技有限公司 一种嘧菌酯的制备方法
CN104725321B (zh) * 2013-12-20 2017-11-21 上海泰禾国际贸易有限公司 一种嘧菌酯中间体的制备方法
CN104230819B (zh) * 2014-09-16 2017-05-03 重庆紫光国际化工有限责任公司 嘧菌酯的合成方法
CN104230822B (zh) * 2014-09-16 2017-03-08 重庆紫光国际化工有限责任公司 嘧菌酯的合成方法
CN104230821B (zh) * 2014-09-16 2016-07-06 重庆紫光国际化工有限责任公司 嘧菌酯的合成方法
CN104230820B (zh) * 2014-09-16 2016-09-28 重庆紫光国际化工有限责任公司 嘧菌酯的合成方法
CN107602480A (zh) * 2017-09-07 2018-01-19 连云港立本作物科技有限公司 嘧菌酯的制备方法
CN109721545B (zh) * 2017-10-31 2020-09-11 南通泰禾化工股份有限公司 一种嘧菌酯中间体的制备方法
CN108516962A (zh) * 2018-05-21 2018-09-11 帕潘纳(北京)科技有限公司 一种嘧菌酯中间体的制备方法
BR112021020912A2 (pt) 2019-04-18 2022-06-07 Upl Ltd Processo para o preparo de compostos de estrobilurina ativos como fungicidas, e intermediários dos mesmos
WO2020212919A1 (fr) * 2019-04-18 2020-10-22 Upl Limited Procédé de préparation d'azoxystrobine et ses intermédiaires
CN112174897B (zh) * 2020-09-18 2021-08-03 广东石油化工学院 一种嘧菌酯中间体的制备方法
CN114685376B (zh) * 2020-12-28 2024-06-07 北京颖泰嘉和生物科技股份有限公司 嘧菌酯中间体的制备方法
CN114957134B (zh) * 2022-05-26 2024-07-16 安徽广信农化股份有限公司 一种制备嘧菌酯及其中间体的方法
CN116120241B (zh) * 2023-02-27 2024-07-16 江苏快达农化股份有限公司 一种复合催化剂合成嘧菌酯中间体的方法
CN116924997A (zh) * 2023-07-14 2023-10-24 江苏剑牌农化股份有限公司 一种嘧菌酯中间体的制备方法

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CN102399195A (zh) * 2011-12-08 2012-04-04 北京颖新泰康国际贸易有限公司 一种嘧菌酯中间体的合成方法

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Cited By (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
AU2014317729B2 (en) * 2013-09-05 2018-03-22 Nutrichem Company Limited Methods for preparing azoxystrobin and intermediate thereof
CN104974097A (zh) * 2015-05-29 2015-10-14 重庆紫光化工股份有限公司 一种嘧菌酯的合成方法
CN104974097B (zh) * 2015-05-29 2018-04-17 重庆紫光化工股份有限公司 一种嘧菌酯的合成方法
CN105396349A (zh) * 2015-11-24 2016-03-16 重庆欣欣向荣精细化工有限公司 用于乙基香兰素的过滤装置
CN105396349B (zh) * 2015-11-24 2024-05-14 重庆欣欣向荣精细化工有限公司 用于乙基香兰素的过滤装置
WO2019178947A1 (fr) * 2018-03-23 2019-09-26 帕潘纳(北京)科技有限公司 Procédé de préparation d'azoxystrobine et de son intermédiaire
US11214552B2 (en) 2018-03-23 2022-01-04 Purpana (Beijing) Technologies Co., Ltd Preparation method for azoxystrobin and intermediate thereof
CN114685375A (zh) * 2020-12-28 2022-07-01 北京颖泰嘉和生物科技股份有限公司 [2-(6-氯嘧啶-4-氧)苯基]-3,3-二甲氧基丙烯酸甲酯的制备方法

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CN102311392B (zh) 2014-01-22

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