WO2014203270A2 - Procédé de préparation de dérivés d'acrylate - Google Patents

Procédé de préparation de dérivés d'acrylate Download PDF

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Publication number
WO2014203270A2
WO2014203270A2 PCT/IN2014/000303 IN2014000303W WO2014203270A2 WO 2014203270 A2 WO2014203270 A2 WO 2014203270A2 IN 2014000303 W IN2014000303 W IN 2014000303W WO 2014203270 A2 WO2014203270 A2 WO 2014203270A2
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WO
WIPO (PCT)
Prior art keywords
reaction
range
solvent
methyl
steps
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Application number
PCT/IN2014/000303
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English (en)
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WO2014203270A3 (fr
Inventor
Vinay DURGAM
Sai Lakshmi BIKKINI
Komali BOTLA
Sivarami Reddy BONTHU
Original Assignee
Bhagiradha Chemicals & Industries Limited
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Publication date
Application filed by Bhagiradha Chemicals & Industries Limited filed Critical Bhagiradha Chemicals & Industries Limited
Publication of WO2014203270A2 publication Critical patent/WO2014203270A2/fr
Publication of WO2014203270A3 publication Critical patent/WO2014203270A3/fr

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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

Definitions

  • the present invention relates to the process for preparation of Methyl 2-[2-(6-chloropyrimidin- 4-yloxy)phenyl]-3,3-dimethoxypropionate and (E) Methyl 2-[2-(6-chloropyrimidine-4-yloxy) phenyl]-3-methoxypropenoate, which are important intermediates in the preparation of Azoxystrobin, a fungicide widely used world over in the protection of food and fruit crops.
  • Methyl 2-[2-(6-chloropyrimidin-4-yloxy)phenyl]-3,3-dimethoxypropionate (structure-1] and (E) Methyl 2-[2-(6-chloropyrimidine-4-yloxy) phenyl]-3-methoxypropenoate (structure -2) can be made in high yielding process and more economical for industrial production.
  • Structure-1 and Structure-2 can be made using 4,6-dichloropyrimidine (structure - 4) and 3-(alpha-methoxy)methylene benzofuran-2(3H)-one (Structure-3) in a solvent and in the presence of sodium methoxide.
  • US patent 5760250 refers to the preparation of Structure -1 and structure-2 in various solvents like acetonitrile, Tetrahydrofuran and methylacetate.
  • the yield mentioned in the above patent is very low and time consuming. Handling of Tetrahydrofuran is uneconomical as distillation losses are more.
  • UK Patent application no GB2291874 refers to the preparation of methyl 3,3-dimethoxy-2-[2- hydroxyphenyl]propionate using structure-3 and sodium methoxide in methanol under low temperature and subsequent neutralization with acetic acid.
  • Major impurity formed in the above process is structure-5 when neutralized with acetic acid and the formed compound doesn't react with 4,6-dichloropyrimidine to yield structure-1 or structure-2.
  • One of the major drawbacks in the process is that methanol is used in excess and under base presence, methanol has to be removed under vacuum at less than or equal to 10C to proceed for the next reaction with 4,6- dichloropyrimidine, if structure-1 and structure-2 are to be prepared, but removal of methanol under 10C temperature industrially is not economical and time consuming, methanol cannot be removed completely as sodium methoxide is present in excess.
  • the above patent also refers to the formation of structure -1 and structure-2 in 51% yielding process. The above process results in the formation of structure-5 compound at significant levels which effects the yield as condensation with 4,6-dichloropyrimidine is done after neutralization with acetic acid. The condensation reaction takes place in Dimethylformamide and under presence of potassium carbonate, which involves different solvents and again for purification another solvent has to be used, which is industrially not feasible.
  • World patent WO9807707 refers mainly for the formation of structure-2 from structure -1 with acetic anhydride and methane sulfonic acid.
  • the above patent also mentions formation of structure- 1 in the presence of sodium methoxide employing Methyl formate as solvent.
  • Methyl formate is very low boiling solvent and industrially distillation losses are unavoidable.
  • the reaction process involves formation of major impurity 4-chloro-6-methoxy pyrimidine (structure-6) which affects the yield.
  • structure-6 major impurity 4-chloro-6-methoxy pyrimidine
  • Chinese patent CN101157657 refers for the formation of Structure-1 and structure-2 using lewis acid such as titanium tetrachloride with trimethylorthoformate or methyl formate for formylating 2-(2-[6-chloropyrimidloxy]phenyl)methylacetate.
  • lewis acid such as titanium tetrachloride with trimethylorthoformate or methyl formate for formylating 2-(2-[6-chloropyrimidloxy]phenyl)methylacetate.
  • lewis acid such as titanium tetrachloride with trimethylorthoformate or methyl formate for formylating 2-(2-[6-chloropyrimidloxy]phenyl)methylacetate.
  • the above process involves usage of titanium tetrachloride in excess, which is unfavorable for the industry and major drawback of this reaction lies in the hydrolysis of the said formylated product. Without completion of hydrolysis the yields of the reaction are quite low.
  • the present invention in this process involves resolving the said above problems.
  • the process is very easy to handle and mostly happens in single solvent without implementing different solvents.
  • the process involves reacting structure-3 with structure-4 in the presence of nonpolar solvent with sodium methoxide in methanol under the action of catalyst which is bicyclic, tricyclic organic catalysts and are very cheap in terms of commercial usuage.
  • the catalyst used in this patent are mostly Tirphenyl phosphine, Adamantane, and Hexamine, and are used for the condensation reaction in nonpolar solvent or polar aprotic solvents in reduced time.
  • Adamantane, tricyclo-[3.3.1.1] decane ring, is a colorless crystalline solid with a characteristic camphor smell. It opputunates the condensation reaction of (E) Methyl 2-[2-[6-chloropyrimidine-4- yloxy) phenyl]-3-methoxypropenoate with o-cyanopehnol at a greater rate.
  • Hexamine which is a tetrahedron and similar to Adamatane cage like structure, with only having Nitrogens molecules on its corner, facilitates the reaction for greater purity and higher conversion to form structure-1 and structure-2. It is a highly water soluble catalyst, which helps in removal of the catalyst by water wash, without carrying forward till the end of product. Triphenyl phosphine is of choice which helps in improving the reaction rate at a higher rate.
  • the present invention mentioned here provides a process for the preparation of structure- 1 and structure-2 comprising the following steps:
  • the said process involves nonpolar or polar aprotic solvents, and inorganics can be removed easily and washed with water.
  • the solvents are more like toluene, dichloroethane, dichloromethane, xylene, dichlorobenzene, chlorobenzene.
  • the base used in the process can be of alkali carbonate or metal hydroxide, metal carbonate, organic carbonates, and organic bases.
  • Base used can be of potassium hydroxide, sodium hydroxide, sodium carbonate, potassium carbonate, triethylamine, trimethylamine, ethylene carbonate, bicarbonates such as sodium bicarbonate, potassium bicarbonate.
  • the ratio of base to be used with respective of structure-3 compound is in the range of 1.0:0.1 to 2.0, preferably in the range of 1.0:0.1 to 1.2 most preferably in the range of 1.0:0.8 to 1.2.
  • the compound of structure-7 can be made easily in the presence of sodium methoxide in methanol, however retaining in the same form, is much more difficult as it may soon convert into structure-5 compound just by acidification or by removing methanol. This reaction for the formation of structure-7 cannot be made easily in other solvents.
  • this invention provides an easy way to form structure-7 compound without forming any impurities, and avoiding methanol removal, as methanol is used in very little quantity.
  • the process describes a simple way of obtaining structure-7 in the presence of sodium methoxide in methanol and in nonpolar solvent.
  • the condensation reaction for the structure-7 compound and structure-4 compound is done in the presence of catalyst in nonpolar solvent and in single pot only.
  • catalyst usually methanol absence can facilitate the condensation reaction fast in polar solvents and in nonpolar solvents reactions happen at a prolonged time.
  • the catalyst facilitate the reaction at a faster rate in nonpolar solvents.
  • the catalyst used in the process is in the range of 1:0.005 to 10, preferably in the range of 1.0:0.005 to 10.
  • the catalyst used in the process is Hexamine or Triphenylphosphine or Adamantane in anhydrous form or in hydrous form with moisture content in the range of 0.1 to 0.5%. Most preferably moisture content to be less than or equal to 0.3%.
  • the Structure-3 to structure-4 ratios are in the range of 1.0:1.0-1.5, preferably in the range of 1.0:1.2.

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
  • Agricultural Chemicals And Associated Chemicals (AREA)

Abstract

La présente invention concerne le procédé de préparation de méthyl 2-[2-(6-chloropyrimidin-4-yloxy) phényl]-3,3-dimethoxypropionate et (E) méthyl 2-[2-(6-chloropyrimidine-4-yloxy) phényl]-3-méthoxypropénoate, qui sont des intermédiaires importants dans la préparation de l'azoxystrobine, un fongicide largement utilisé dans le monde dans la protection d'aliments et de cultures fruitières.
PCT/IN2014/000303 2013-06-19 2014-05-06 Procédé de préparation de dérivés d'acrylate WO2014203270A2 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
IN2658/CHE/2013 2013-06-19
IN2658CH2013 2013-06-19

Publications (2)

Publication Number Publication Date
WO2014203270A2 true WO2014203270A2 (fr) 2014-12-24
WO2014203270A3 WO2014203270A3 (fr) 2015-02-19

Family

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Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/IN2014/000303 WO2014203270A2 (fr) 2013-06-19 2014-05-06 Procédé de préparation de dérivés d'acrylate

Country Status (1)

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WO (1) WO2014203270A2 (fr)

Cited By (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN104926736A (zh) * 2015-05-29 2015-09-23 重庆紫光化工股份有限公司 一种嘧菌酯及其中间体的合成方法
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
AU2018253450B2 (en) * 2017-10-31 2019-09-26 Cac Nantong Chemical Co., Ltd Method for preparing azoxystrobin intermediates
CN114685376A (zh) * 2020-12-28 2022-07-01 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

Family Cites Families (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GB9415291D0 (en) * 1994-07-28 1994-09-21 Zeneca Ltd Chemical process
GB0508422D0 (en) * 2005-04-26 2005-06-01 Syngenta Ltd Chemical process
CN101973943B (zh) * 2010-09-26 2012-11-21 重庆紫光化工股份有限公司 (e)-2-[2-(6-氯嘧啶-4-基氧)苯基]-3-甲氧基丙烯酸甲酯的制备方法

Cited By (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN104926736A (zh) * 2015-05-29 2015-09-23 重庆紫光化工股份有限公司 一种嘧菌酯及其中间体的合成方法
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
AU2018253450B2 (en) * 2017-10-31 2019-09-26 Cac Nantong Chemical Co., Ltd Method for preparing azoxystrobin intermediates
CN114685376A (zh) * 2020-12-28 2022-07-01 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
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

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