WO2019233209A1 - 一种s体茚虫威的制备方法 - Google Patents

一种s体茚虫威的制备方法 Download PDF

Info

Publication number
WO2019233209A1
WO2019233209A1 PCT/CN2019/084224 CN2019084224W WO2019233209A1 WO 2019233209 A1 WO2019233209 A1 WO 2019233209A1 CN 2019084224 W CN2019084224 W CN 2019084224W WO 2019233209 A1 WO2019233209 A1 WO 2019233209A1
Authority
WO
WIPO (PCT)
Prior art keywords
zirconium
catalyst
indoxacarb
reaction
tert
Prior art date
Application number
PCT/CN2019/084224
Other languages
English (en)
French (fr)
Inventor
薄蕾芳
成道泉
刘建成
冯培良
刘花敏
王中洋
Original Assignee
京博农化科技有限公司
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 京博农化科技有限公司 filed Critical 京博农化科技有限公司
Priority to EP19815254.8A priority Critical patent/EP3804853B1/en
Priority to US16/954,081 priority patent/US11639336B2/en
Publication of WO2019233209A1 publication Critical patent/WO2019233209A1/zh

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D273/00—Heterocyclic compounds containing rings having nitrogen and oxygen atoms as the only ring hetero atoms, not provided for by groups C07D261/00 - C07D271/00
    • C07D273/02—Heterocyclic compounds containing rings having nitrogen and oxygen atoms as the only ring hetero atoms, not provided for by groups C07D261/00 - C07D271/00 having two nitrogen atoms and only one oxygen atom
    • C07D273/04—Six-membered rings
    • C—CHEMISTRY; METALLURGY
    • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08G—MACROMOLECULAR COMPOUNDS OBTAINED OTHERWISE THAN BY REACTIONS ONLY INVOLVING UNSATURATED CARBON-TO-CARBON BONDS
    • C08G12/00—Condensation polymers of aldehydes or ketones with only compounds containing hydrogen attached to nitrogen
    • C08G12/02—Condensation polymers of aldehydes or ketones with only compounds containing hydrogen attached to nitrogen of aldehydes
    • C08G12/04—Condensation polymers of aldehydes or ketones with only compounds containing hydrogen attached to nitrogen of aldehydes with acyclic or carbocyclic compounds
    • C08G12/06—Amines
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J31/00—Catalysts comprising hydrides, coordination complexes or organic compounds
    • B01J31/16—Catalysts comprising hydrides, coordination complexes or organic compounds containing coordination complexes
    • B01J31/22—Organic complexes
    • B01J31/2204—Organic complexes the ligands containing oxygen or sulfur as complexing atoms
    • B01J31/2208—Oxygen, e.g. acetylacetonates
    • B01J31/2217—At least one oxygen and one nitrogen atom present as complexing atoms in an at least bidentate or bridging ligand
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J31/00—Catalysts comprising hydrides, coordination complexes or organic compounds
    • B01J31/40—Regeneration or reactivation
    • B01J31/4015—Regeneration or reactivation of catalysts containing metals
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
    • C07B53/00—Asymmetric syntheses
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C67/00—Preparation of carboxylic acid esters
    • C07C67/30—Preparation of carboxylic acid esters by modifying the acid moiety of the ester, such modification not being an introduction of an ester group
    • C07C67/31—Preparation of carboxylic acid esters by modifying the acid moiety of the ester, such modification not being an introduction of an ester group by introduction of functional groups containing oxygen only in singly bound form
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J2531/00—Additional information regarding catalytic systems classified in B01J31/00
    • B01J2531/02—Compositional aspects of complexes used, e.g. polynuclearity
    • B01J2531/0213—Complexes without C-metal linkages
    • B01J2531/0216—Bi- or polynuclear complexes, i.e. comprising two or more metal coordination centres, without metal-metal bonds, e.g. Cp(Lx)Zr-imidazole-Zr(Lx)Cp
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J2531/00—Additional information regarding catalytic systems classified in B01J31/00
    • B01J2531/02—Compositional aspects of complexes used, e.g. polynuclearity
    • B01J2531/0238—Complexes comprising multidentate ligands, i.e. more than 2 ionic or coordinative bonds from the central metal to the ligand, the latter having at least two donor atoms, e.g. N, O, S, P
    • B01J2531/0241—Rigid ligands, e.g. extended sp2-carbon frameworks or geminal di- or trisubstitution
    • B01J2531/0252—Salen ligands or analogues, e.g. derived from ethylenediamine and salicylaldehyde
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J2531/00—Additional information regarding catalytic systems classified in B01J31/00
    • B01J2531/40—Complexes comprising metals of Group IV (IVA or IVB) as the central metal
    • B01J2531/48—Zirconium
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J31/00—Catalysts comprising hydrides, coordination complexes or organic compounds
    • B01J31/16—Catalysts comprising hydrides, coordination complexes or organic compounds containing coordination complexes
    • B01J31/1691—Coordination polymers, e.g. metal-organic frameworks [MOF]
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J31/00—Catalysts comprising hydrides, coordination complexes or organic compounds
    • B01J31/16—Catalysts comprising hydrides, coordination complexes or organic compounds containing coordination complexes
    • B01J31/22—Organic complexes
    • B01J31/2204—Organic complexes the ligands containing oxygen or sulfur as complexing atoms
    • B01J31/2208—Oxygen, e.g. acetylacetonates
    • B01J31/2226—Anionic ligands, i.e. the overall ligand carries at least one formal negative charge
    • B01J31/2243—At least one oxygen and one nitrogen atom present as complexing atoms in an at least bidentate or bridging ligand
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
    • C07B2200/00—Indexing scheme relating to specific properties of organic compounds
    • C07B2200/07—Optical isomers
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C2602/00—Systems containing two condensed rings
    • C07C2602/02—Systems containing two condensed rings the rings having only two atoms in common
    • C07C2602/04—One of the condensed rings being a six-membered aromatic ring
    • C07C2602/08—One of the condensed rings being a six-membered aromatic ring the other ring being five-membered, e.g. indane

Definitions

  • the invention relates to the field of chemical synthesis, and specifically discloses a method for preparing S body indoxacarb.
  • Indoxacarb is a new type of high-efficiency, low-toxic oxadiazine insecticide developed by DuPont of the United States. It has dual effects of contact killing and stomach toxicity, and effectively solves the problem of resistance to pests. It has no cross-resistance with other insecticides such as pyrethroids, organophosphorus, and urethanes, which can well solve the problems of rice leaf roller, pupae, and resistant diamondback moth that are difficult to prevent in the market today. In addition, indoxacarb has a very wide insecticidal spectrum, one medicine and multiple preventions. While controlling nocturnal moth pests, it also has a good inhibitory effect on blind maggots, so it is a good comprehensive management tool.
  • indoxacarb was successively registered and listed in the United States, France, China and many other countries as "risk-reducing products" in 2001. It is the latest variety of green pesticides and is also the Ministry of Agriculture of China. Large-scale demonstration and promotion of alternative high-toxicity, high-residue pesticide varieties. In 2008, its global sales reached more than 200 million US dollars.
  • the purpose of the present invention is to overcome the shortcomings of the prior art, and provide a brand-new catalyst and a method for preparing S body indoxacarb using the catalyst.
  • the catalyst includes 3-tert-butyl-5-chloromethyl salicylate. Aldehyde and cyclohexanediamine are prepared as raw materials, and the catalyst is used to replace the original cinchona base catalysts such as sinkonin, and is applied to tert-butyl hydroperoxide and 5-chloro-2-methoxycarbonyl-1-indene
  • the selectivity in the process of asymmetric synthesis is greatly improved, and the S content is increased from 75% to more than 98%, and the recycling of highly efficient chiral catalyst is realized, which greatly reduces the production cost.
  • the synthesis process of the catalyst is simple and is favorable for industrialization, which lays a good foundation for the production of high-quality indoxacarb.
  • the inventor first provided a brand new chiral catalyst containing metal zirconium.
  • the preparation reaction equation is as follows:
  • the cyclohexanediamine is chiral cyclohexanediamine, the molar ratio of 3-tert-butyl-5-chloromethylsalicylaldehyde to cyclohexanediamine is 1: 1-1, and the amount of solvent is 3-tert-butyl -5-chloromethyl salicylaldehyde is 4-6 times the mass;
  • the solvent is selected from the group consisting of methanol, ethanol, dichloromethane, and dichloroethane;
  • methanol is used
  • the solvent is selected from the group consisting of toluene, xylene, dichloroethane, n-hexane, and t-butanol;
  • toluene is used
  • the reducing agent is selected from one of sodium borohydride, potassium borohydride, and lithium aluminum hydride; and the molar ratio of the reducing agent to 3-tert-butyl-5-chloromethylsalicylic aldehyde is 1-1.2: 1;
  • the zirconium compound is selected from zirconium hydroxide, zirconyl chloride, zirconium oxide, zirconium chloride, zirconium acetylacetonate, zirconium trifluoroacetylacetone, zirconium n-propanolate, zirconium tert-butoxide, zirconium phosphate, and zirconium bromide
  • zirconium hydroxide zirconyl chloride, zirconium oxide, zirconium chloride, zirconium acetylacetonate, zirconium trifluoroacetylacetone, zirconium n-propanolate, zirconium tert-butoxide, zirconium phosphate, and zirconium bromide
  • the preparation process of S-body indoxacarb is as follows: (This process can refer to the 2014 master's degree awarded by Zhejiang University (The synthetic route disclosed in the paper "Synthesis of Indoxacarb, a Novel and Highly Efficient Chiral Insecticide, and Its Polymorphic Forms")
  • tert-butyl hydroperoxide and 5-chloro-2-methoxycarbonyl-1-indenone ester were added for an asymmetric synthesis reaction, in which 5-chloro-2-methoxycarbonyl-1 -The molar ratio of indenone ester: tert-butyl hydroperoxide: catalyst is 1: 1.2-1.5: 0.05-0.1, and the temperature can be raised to 60-120 ° C under reflux for 4 hours. The obtained mixture can be filtered to recover the polymer catalyst.
  • the obtained filtrate can be distilled under reduced pressure to obtain the key intermediate 5-chloro-2-methoxycarbonyl-2-hydroxy-1-indanone; at the same time, the recovered catalyst is put into the toluene solvent to form a suspension, and can continue to participate The above asymmetric synthesis reaction;
  • the catalyst and the method provided in the present invention can be recycled and used, which greatly reduces the production cost.
  • the catalyst has a simple synthesis process, is conducive to industrialization, and lays a good foundation for producing high-quality indoxacarb.
  • the catalyst provided by the present invention can be used to prepare an indoxacarb drug with an S-body content ⁇ 98%.
  • the high-efficiency chiral catalyst replaced the original cinchona base and other catalysts, which greatly improved the selectivity in asymmetric synthesis, and the S-body content was increased from 75% to more than 98%.
  • the preparation of chiral catalysts introduces metal zirconium compounds, which greatly improves the reaction speed of asymmetric reactions. The reaction speed is shortened from the original 24 hours to 4 hours.
  • the catalyst has a simple synthesis process and is conducive to industrialization, laying a foundation for the production of high-quality indoxacarb A good foundation.
  • Embodiment 1 A chiral catalyst containing metal zirconium and a method for preparing S body indoxacarb using the catalyst.
  • the preparation method is as follows:
  • step (3) A 2000 mL clean, anhydrous reaction flask was charged with the ligand polymer in step (2), and then 50 mL of toluene and 3.78 g (0.1 mol) of sodium borohydride were added, and the reaction was heated at reflux.
  • the method for preparing S body indoxacarb using the above catalyst can adopt the conventional synthetic route disclosed in the 2014 master's degree thesis "Synthesis of Indoxacarb, a Novel and Highly Efficient Chiral Insecticide, and Its Polymorphic Forms". among them:
  • Example 2 A chiral catalyst containing metal zirconium and a method for preparing S body indoxacarb using the catalyst, the preparation method is as follows:
  • step (3) A 2000 mL clean, anhydrous reaction flask was charged with the ligand polymer in step (2), and then 50 mL of toluene and 5.4 g (0.1 mol) of potassium borohydride were added, and the reaction was heated at reflux.
  • the method for preparing S body indoxacarb using the above catalyst can adopt the conventional synthetic route disclosed in the 2014 master's degree thesis "Synthesis of Indoxacarb, a Novel and Highly Efficient Chiral Insecticide, and Its Polymorphic Forms". among them:
  • Example 2 The catalyst recovered by filtration in Example 2 was added to toluene, and then 113 g of tert-butyl hydroperoxide and 224 g of 5-chloro-2-methoxycarbonyl-1-indenone ester and 1200 mL of toluene were added for an asymmetric synthesis reaction, and the temperature was raised. The reaction was refluxed at 110 ° C for 4 hours. After the reaction is completed, the metal polymer catalyst is recovered by filtration. The obtained filtrate can be distilled under reduced pressure to obtain the key intermediate 5-chloro-2-methoxycarbonyl-2-hydroxy-1-indanone. At the same time, the recovered catalyst is put into 50 mL. A suspension was formed in the toluene solvent to continue the asymmetric synthesis reaction; the prepared intermediate was prepared according to the conventional prior art to obtain S body indoxacarb.
  • the catalyst provided by the present invention has a stable structure and is not easy to be lost during the reaction. It is verified by small tests that the indoxacarb S-body content obtained after ten application is still higher than the production level of DuPont (90% S-body content). According to the calculation of the catalyst applied ten times, the cost of using the catalyst is more than 30,000 yuan lower than that of DuPont, which has greater economic and environmental benefits.
  • the catalyst provided by the present invention improves the selectivity in the asymmetric synthesis process, and the S body content is increased from 75% to more than 98%.
  • the preparation of chiral catalysts introduces metal zirconium compounds, which greatly improves the reaction speed of asymmetric reactions.
  • the reaction speed is shortened from the original 24 hours to 4 hours.
  • it is combined with a chiral diamine ligand to enhance the Selectivity during symmetric synthesis.

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Engineering & Computer Science (AREA)
  • Materials Engineering (AREA)
  • Health & Medical Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Polymers & Plastics (AREA)
  • Inorganic Chemistry (AREA)
  • Catalysts (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)

Abstract

催化剂以及利用该催化剂制备S体茚虫威的方法，该催化剂以入3-叔丁基-5-氯甲基水杨醛和环己二胺为原料制备而成，并以该催化剂代替了原来的辛克宁等金鸡纳碱类催化剂，应用于叔丁基过氧化氢和5-氯-2-甲氧羰基-1-茚酮酯的不对称合成反应中，大大提高了不对称合成过程中的选择性，S体含量从75％提升至98％以上，且实现了高效手性催化剂的循环利用，大大降低了生产成本，该催化剂的合成工艺简单，利于工业化，为生产高品质的茚虫威奠定了良好的基础。

Description

一种S体茚虫威的制备方法 技术领域
本发明涉及化学合成领域，具体公开了一种S体茚虫威的制备方法。
背景技术
茚虫威为美国杜邦公司研发的一种新型、高效、低毒噁二嗪类杀虫剂，具有触杀与胃毒双重功效，有效解决抗性害虫。与其他杀虫剂如菊酯、有机磷、氨基甲酸酯类均无交互抗性，可以很好的解决目前市场上难防的稻纵卷叶螟、二化螟及抗性小菜蛾问题。此外，茚虫威具有极宽的杀虫谱，一药多防，在防治夜蛾类害虫的同时，对盲蝽蟓等还具有很好的抑制作用，因此是一种很好的综合治理工具，可以很好的解决目前多种农药混用后的残留及环境污染问题。茚虫威由于其独特的作用机制、市场前景广阔，2001年在美国、法国、中国等世界许多国家作为“降低风险产品”陆续登记上市，是目前绿色杀虫剂的最新品种，也是我国农业部大面积示范推广的替代高毒、高残留农药品种。2008年其全球销售额达到2亿美元以上。
该产品于1991年12月21日在中国申请专利，2011年12月21日专利到期。随着茚虫威专利期的结束，国内多家企业开始了茚虫威产品的合成工艺研究与生产，但合成得到的茚虫威原药为S与R的混合体，S:R＝3:1，其中原药中的R体没有药效，造成环境污染，用药成本高。因此开发一种S体茚虫威原药的合成方法成为国内外研究的热点。目前合成茚虫威原药使用的催化剂主要有以下两条：
第一，采用辛克宁等金鸡纳碱类催化剂，但是该类催化剂效率低下，合成得到的茚虫威原药S体含量在70％左右；
第二，采用金属配合物类催化剂，2007年美国杜邦公司报道了金属锆催化剂，但是该类催化剂不能回收利用，生产成本较高，且得到的茚虫威原药S体含量在90％左右；
因此如何克服上述茚虫威原药S体合成过程中催化剂和合成方法存在的缺陷成为本领域亟待解决的问题之一。
发明内容
本发明的目的在于克服现有技术缺点，提供了一种全新的催化剂以及利用该催化剂制备S体茚虫威的方法，所述的催化剂以入3-叔丁基-5-氯甲基水杨醛和环己二胺为原料制备而成，并以该催化剂代替了原来的辛克宁等金鸡纳碱类催化剂，应用于叔丁基过氧化氢和5-氯-2-甲氧羰基-1-茚酮酯的不对称合成反应中，大大提高了不对称合成过程中的选择性，S体含量从75％提升至98％以上，且实现了高效手性催化剂的循环利用，大大降低了生产成本，该催化剂的合成工艺简单，利于工业化，为生产高品质的茚虫威奠定了良好的基础。
本发明技术方案如下：
发明人首先提供了一种全新的含金属锆的手性催化剂，其制备反应方程式如下：
Figure PCTCN2019084224-appb-000001
具体步骤为：
(1)、20-30℃下向反应瓶中加入3-叔丁基-5-氯甲基水杨醛和溶剂，然后向体系内滴加环己二胺，控制滴加速度为0.1mL/min；
其中环己二胺为手性环己二胺，3-叔丁基-5-氯甲基水杨醛与环己二胺的摩尔比为1:1-1.5，溶剂用量为3-叔丁基-5-氯甲基水杨醛质量4-6倍；
所述的溶剂选自甲醇、乙醇、二氯甲烷、二氯乙烷中的一种；
优选采用甲醇；
(2)、滴加完成升温至40-80℃回流反应，反应结束后，降温至0-20℃，过滤得配体聚合物，烘干称重；
(3)、向反应瓶中投入上步获得的配体聚合物和2倍配体聚合物质量的溶剂，然后投入还原剂，升温至80-140℃，进行回流反应4-6小时；
所述的溶剂选自甲苯、二甲苯、二氯乙烷、正己烷、叔丁醇中的一种；
优选采用甲苯；
所述的还原剂选自硼氢化钠、硼氢化钾、氢化铝锂中的一种；其用量与3-叔丁基-5-氯甲基水杨醛的摩尔比为1-1.2:1；
(4)、向上述体系中加入金属锆化合物，充分溶胀后，升温至80-100℃，保温反应2-4小时得聚合催化剂溶液；
其中所述的锆化合物选自氢氧化锆、氯化氧锆、氧化锆、氯化锆、乙酰丙酮锆、三氟乙酰丙酮锆、正丙醇锆、叔丁醇锆、磷酸锆、溴化锆中的一种；
优选采用乙酰丙酮锆；
且所述锆化合物：3-叔丁基-5-氯甲基水杨醛的摩尔比为1:1-2；
上述制备工艺中：
首先，将3-叔丁基-5-氯甲基水杨醛和甲醇投入反应瓶中，然后向体系中滴加环己二胺，环己二胺在反应过程中起到桥梁连接的作用，将不同的3-叔丁基-5-氯甲基水杨醛连接成配合物单体，通过控制环己二胺的滴加速度，使配合物的单体生成均匀可控；然后升温反应使不同的单体发生聚合反应，长时间回流使单体充分聚合，待聚合物全部生成后，由于聚合物的分子量较大，且在溶剂中的溶解性较差，聚合物在体系中逐渐析出，降温过滤得到聚合物配体。
其次，向反应瓶中加入甲苯和上述的聚合物配体，然后加入还原剂使C＝N进 行加氢还原，使N提供电子对便于配位，然后向体系中加入金属锆化合物，由于聚合物在甲苯中的溶解性较差，使其充分溶胀浸泡后，通过升温高温反应，使金属钻入聚合物配体中，发生配位反应，生成聚合有机配体的配合物催化剂。由于聚合物配体不溶于甲苯，生成的配合物催化剂悬浮于甲苯溶剂中。可以以其为反应体系直接进行后续的S体茚虫威制备，具体如下：
在获得了上述的催化剂之后，发明人又将其应用到了S体茚虫威的制备过程中，所述S体茚虫威的制备过程如下：(该过程可参考浙江大学2014年度授予的硕士学位论文《新颖高效手性杀虫剂茚虫威的合成工艺及其多晶型研究》公开的合成路线)
Figure PCTCN2019084224-appb-000002
上述反应过程与常规技术类似，但是其中5-氯-2-甲氧羰基-1-茚酮酯转化为5-氯-2-甲氧羰基-2-羟基-1-茚酮的过程中采用了上述的催化剂，其具体反应过程如下：
上述反应为不对称合成反应，具体步骤是：
向上述方法获得的聚合催化剂溶液中加入叔丁基过氧化氢和5-氯-2-甲氧羰基-1-茚酮酯进行不对称合成反应，其中5-氯-2-甲氧羰基-1-茚酮酯：叔丁基过氧化氢：催化剂的摩尔比为1:1.2-1.5：0.05-0.1，升温至60-120℃回流反应4小时即可，所获得的混合物经过滤回收聚合物催化剂，获得的滤液经减压蒸馏即 可获得关键中间体5-氯-2-甲氧羰基-2-羟基-1-茚酮；同时将回收的催化剂投入到甲苯溶剂中形成悬浮液即可继续参与上述不对称合成反应；
获得了上述的5-氯-2-甲氧羰基-2-羟基-1-茚酮后，即可按照上述的常规合成路线与肼基甲酸苄酯及二乙氧基甲烷反应，最后加氢脱保护与4-三氟甲氧基苯基氨基甲酸甲酯合成S体茚虫威原药。
最终获得的S体茚虫威经检测，其中的S体茚虫威含量达到98％以上，远高于现有采用辛克宁等金鸡纳碱类催化剂的70％左右含量；也明显高于美国杜邦公司报道的金属锆催化剂制备的茚虫威原药S体含量在90％的水平；
同时，本发明所述提供的上述催化剂和方法，催化剂可以循环利用，大大降低了生产成本，该催化剂的合成工艺简单，利于工业化，为生产高品质的茚虫威奠定了良好的基础。
综上所述，采用本发明提供的催化剂可制备S体含量≥98％的茚虫威原药。用高效手性催化剂代替了原来的辛克宁等金鸡纳碱类催化剂，大大提高了不对称合成过程中的选择性，S体含量从75％提升至98％以上。其中手性催化剂的制备引入了金属锆类化合物，大大提升了不对称反应的反应速度，反应速度从原来的24小时缩短为4小时，同时配以手性二胺类体配体，增强了不对称合成过程中的选择性，并且有机聚合配体的引入实现了高效手性催化剂的循环利用，大大降低了生产成本，该催化剂的合成工艺简单，利于工业化，为生产高品质的茚虫威奠定了良好的基础。
具体实施方式
实施例1一种含金属锆的手性催化剂及利用该催化剂制备S体茚虫威的方法，其制备方法如下：
(1)100mL干净无水的反应瓶中加入22.65g(0.1mol)3-叔丁基-5-氯甲基水杨醛，然后加入50mL甲醇，然后称取11.4g(0.1mol)环己二胺，于20-25℃缓慢滴加。
(2)滴加完成升温至65-70℃回流反应，反应结束后，降温至10℃，过滤得 配体聚合物，烘干称重。
(3)2000mL干净无水的反应瓶投入步骤(2)中的配体聚合物，然后加入50mL甲苯和3.78g(0.1mol)硼氢化钠，升温回流反应。
(4)向上述反应体系中加入24.35g(0.05mol)乙酰丙酮锆，充分浸泡后升温至80℃，保温反应得聚合催化剂的甲苯溶液。
利用上述催化剂制备S体茚虫威的方法，可采用浙江大学2014年度授予的硕士学位论文《新颖高效手性杀虫剂茚虫威的合成工艺及其多晶型研究》公开的常规合成路线，其中：
(5)向上述步骤(4)获得的催化剂甲苯溶液中加入225g叔丁基过氧化氢和449g5-氯-2-甲氧羰基-1-茚酮酯以及1000mL甲苯进行不对称合成反应，升温110℃回流反应4小时；反应完成后过滤回收金属聚合物催化剂，获得的滤液经减压蒸馏即可获得关键中间体5-氯-2-甲氧羰基-2-羟基-1-茚酮；同时将回收的化剂投入到50mL甲苯溶剂中形成悬浮液继续进行不对称合成反应；
(6)将上述减压蒸馏浓缩得关键中间体5-氯-2-甲氧羰基-2-羟基-1-茚酮，按照说明书中所示的现有合成路线与肼基甲酸苄酯及二乙氧基甲烷反应，最后加氢脱保护与4-三氟甲氧基苯基氨基甲酸甲酯合成S体茚虫威原药，经检测S体含量为98.6％。
实施例2一种含金属锆的手性催化剂及利用该催化剂制备S体茚虫威的方法，其制备方法如下：
(1)100mL干净无水的反应瓶中加入22.65g(0.1mol)3-叔丁基-5-氯甲基水杨醛，然后加入50mL甲醇，然后称取17.1g(0.15mol)环己二胺，于20-25℃缓慢滴加。
(2)滴加完成升温至65-70℃回流反应，反应结束后，降温至10℃，过滤得配体聚合物，烘干称重。
(3)2000mL干净无水的反应瓶投入步骤(2)中的配体聚合物，然后加入50mL甲苯和5.4g(0.1mol)硼氢化钾，升温回流反应。
(4)向上述反应体系中加入24.35g(0.05mol)乙酰丙酮锆，充分溶胀后升温至80℃，保温反应得聚合催化剂的甲苯溶液；
利用上述催化剂制备S体茚虫威的方法，可采用浙江大学2014年度授予的硕士学位论文《新颖高效手性杀虫剂茚虫威的合成工艺及其多晶型研究》公开的常规合成路线，其中：
(5)向上述步骤(4)获得的催化剂甲苯溶液中加入113g叔丁基过氧化氢和224g5-氯-2-甲氧羰基-1-茚酮酯以及1200mL甲苯进行不对称合成反应，升温110℃回流反应4小时。反应完成后过滤回收金属聚合物催化剂，获得的滤液经减压蒸馏即可获得关键中间体5-氯-2-甲氧羰基-2-羟基-1-茚酮；同时将回收的催化剂投入到50mL甲苯溶剂中形成悬浮液继续进行不对称合成反应；
(6)将上述减压蒸馏浓缩得关键中间体5-氯-2-甲氧羰基-2-羟基-1-茚酮，按照说明书中所示的现有合成路线与肼基甲酸苄酯及二乙氧基甲烷反应，最后加氢脱保护与4-三氟甲氧基苯基氨基甲酸甲酯合成S体茚虫威原药，经检测S体含量为98.9％。
实施例3.金属聚合物催化剂的回收利用
将实施例2中过滤回收得的催化剂加入到甲苯中，然后加入113g叔丁基过氧化氢和224g5-氯-2-甲氧羰基-1-茚酮酯以及1200mL甲苯进行不对称合成反应，升温110℃回流反应4小时。反应完成后过滤回收金属聚合物催化剂，获得的滤液经减压蒸馏即可获得关键中间体5-氯-2-甲氧羰基-2-羟基-1-茚酮；同时将回收的催化剂投入到50mL甲苯溶剂中形成悬浮液继续进行不对称合成反应；制备得到的中间体按照常规现有技术制备得到S体茚虫威。
套用次数与反应收率和S体含量的相关实验结果如下表所示：
序号 收率(％) S体含量(％) 备注
1 58.1 98.9 第一次套用
2 57.9 98.8 第二次套用
3 57.8 98.7 第三次套用
4 57.7 98.5 第四次套用
5 57.5 98.2 第五次套用
6 57.4 97.8 第六次套用
7 57.3 97.3 第七次套用
8 57.1 96.9 第八次套用
9 57 96.4 第九次套用
10 56.6 96 第十次套用
可见本发明所提供的催化剂结构稳定，反应过程中不易损耗，小试验证套用十次后得到的茚虫威S体含量仍高于杜邦公司(90％S体含量)生产水平。按照催化剂套用十次进行核算，该催化剂使用成本较杜邦公司下降3万元以上，具有较大的经济效益和环境效益。
综上所述，可见本发明所提供的催化剂提高了不对称合成过程中的选择性，S体含量从75％提升至98％以上。其中手性催化剂的制备引入了金属锆类化合物，大大提升了不对称反应的反应速度，反应速度从原来的24小时缩短为4小时，同时配以手性二胺类体配体，增强了不对称合成过程中的选择性。

Claims (8)

  1. 一种S体茚虫威的制备方法：其特征是：采用含金属锆的手性催化剂对不对称合成反应进行催化，所述的含金属锆的手性催化剂的制备方法如下：(1)、20-30℃下向反应瓶中加入3-叔丁基-5-氯甲基水杨醛和溶剂，然后向体系内滴加环己二胺，控制滴加速度为0.1mL/min；(2)、滴加完成升温至40-80℃回流反应，反应结束后，降温至0-20℃，过滤得配体聚合物，烘干称重；(3)、向反应瓶中投入上步获得的配体聚合物和2倍配体聚合物质量的溶剂，然后投入还原剂，升温至80-140℃，进行回流反应4-6小时；(4)、向上述体系中加入金属锆化合物，充分溶胀后，升温至80-100℃，保温反应2-4小时得聚合催化剂溶液；其反应方程式如下：
    Figure PCTCN2019084224-appb-100001
  2. 根据权利要求1所述S体茚虫威的制备方法，其特征是：还包括如下步骤：向上述方法获得的聚合催化剂溶液中加入叔丁基过氧化氢和5-氯-2-甲氧羰基-1-茚酮酯进行不对称合成反应，其中5-氯-2-甲氧羰基-1-茚酮酯：叔丁基过氧化氢：催化剂的摩尔比为1:1.2-1.5：0.05-0.1，升温至60-120℃回流反应4小时即可，所获得的混合物 经过滤回收聚合物催化剂，获得的滤液经减压蒸馏即可获得关键中间体5-氯-2-甲氧羰基-2-羟基-1-茚酮；同时将回收的催化剂投入到甲苯溶剂中形成悬浮液即可继续参与上述不对称合成反应；获得了上述的5-氯-2-甲氧羰基-2-羟基-1-茚酮后，即可按照常规合成路线与肼基甲酸苄酯及二乙氧基甲烷反应，最后加氢脱保护与4-三氟甲氧基苯基氨基甲酸甲酯合成S体茚虫威原药。
  3. 根据权利要求1所述S体茚虫威的制备方法，其特征是：其中步骤(1)中所述环己二胺为手性环己二胺，3-叔丁基-5-氯甲基水杨醛与环己二胺的摩尔比为1:1-1.5，溶剂用量为3-叔丁基-5-氯甲基水杨醛质量4-6倍；所述的溶剂选自甲醇、乙醇、二氯甲烷、二氯乙烷中的一种。
  4. 根据权利要求3所述S体茚虫威的制备方法，其特征是：所述的溶剂选自甲醇。
  5. 根据权利要求1所述S体茚虫威的制备方法，其特征是：其中步骤(3)中所述的溶剂选自甲苯、二甲苯、二氯乙烷、正己烷、叔丁醇中的一种；所述的还原剂选自硼氢化钠、硼氢化钾、氢化铝锂中的一种；其用量与3-叔丁基-5-氯甲基水杨醛的摩尔比为1-1.2:1。
  6. 根据权利要求5所述S体茚虫威的制备方法，其特征是：步骤(3)中所述的溶剂为甲苯。
  7. 根据权利要求1所述S体茚虫威的制备方法，其特征是：其中步骤(4)中所述的锆化合物选自氢氧化锆、氯化氧锆、氧化锆、氯化锆、乙酰丙酮锆、三氟乙酰丙酮锆、正丙醇锆、叔丁醇锆、磷酸锆、溴化锆中的一种；且所述锆化合物：3-叔丁基-5-氯甲基水杨醛的摩尔比为1:1-2。
  8. 根据权利要求7所述S体茚虫威的制备方法，其特征是：其中步骤(4)中所述的锆化合物为乙酰丙酮锆。
PCT/CN2019/084224 2018-06-08 2019-04-25 一种s体茚虫威的制备方法 WO2019233209A1 (zh)

Priority Applications (2)

Application Number Priority Date Filing Date Title
EP19815254.8A EP3804853B1 (en) 2018-06-08 2019-04-25 Preparation method for s-indoxacarb
US16/954,081 US11639336B2 (en) 2018-06-08 2019-04-25 Preparation method for S-indoxacarb

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
CN201810591874.7A CN109701655B (zh) 2018-06-08 2018-06-08 一种s体茚虫威的制备方法
CN201810591874.7 2018-06-08

Publications (1)

Publication Number Publication Date
WO2019233209A1 true WO2019233209A1 (zh) 2019-12-12

Family

ID=66253743

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/CN2019/084224 WO2019233209A1 (zh) 2018-06-08 2019-04-25 一种s体茚虫威的制备方法

Country Status (4)

Country Link
US (1) US11639336B2 (zh)
EP (1) EP3804853B1 (zh)
CN (1) CN109701655B (zh)
WO (1) WO2019233209A1 (zh)

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN111747850A (zh) * 2020-08-06 2020-10-09 山东京博生物科技有限公司 一锅法合成5-氯-1-氧代-2，3-二氢-1h-茚-2-羧酸甲酯的方法
CN114671749A (zh) * 2022-04-01 2022-06-28 国科广化韶关新材料研究院 一种含锆环保型聚氨酯催化剂的制备方法及其应用

Families Citing this family (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN110511217B (zh) * 2019-09-25 2022-01-28 京博农化科技有限公司 一种催化茚虫威关键中间体合成的催化剂及其应用
CN113277948B (zh) * 2021-05-24 2022-09-27 京博农化科技有限公司 一种制备高含量茚虫威中间体的制备方法
CN114181080B (zh) * 2021-12-21 2023-11-07 阜新睿光氟化学有限公司 5-氯-2-甲氧羰基-2-羟基-1-茚酮的绿色制备方法

Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN1630555A (zh) * 2001-06-29 2005-06-22 纳幕尔杜邦公司 应用锆催化剂羟基化β－二羰基化合物的方法
CN101062903A (zh) * 2001-06-29 2007-10-31 纳幕尔杜邦公司 锆配合物催化剂及其手性配体
CN106397351A (zh) * 2016-08-31 2017-02-15 京博农化科技股份有限公司 一种茚虫威中间体的制备方法

Family Cites Families (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US8207365B2 (en) * 2005-03-14 2012-06-26 Georgia Tech Research Corporation Polymeric salen compounds and methods thereof
CN102631946B (zh) * 2012-04-09 2014-01-08 复旦大学 Ⅳb族[n,n,o,o]配合物烯烃聚合催化剂及其制备方法和应用
CN104262285B (zh) * 2014-07-24 2016-08-17 浙江大学 农用杀虫剂茚虫威中间体的合成法
CN105521826B (zh) * 2015-12-08 2018-12-21 大连理工大学 一种锆催化剂及其制备手性α-羟基-β-酮酸酯化合物的方法

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN1630555A (zh) * 2001-06-29 2005-06-22 纳幕尔杜邦公司 应用锆催化剂羟基化β－二羰基化合物的方法
CN101062903A (zh) * 2001-06-29 2007-10-31 纳幕尔杜邦公司 锆配合物催化剂及其手性配体
CN106397351A (zh) * 2016-08-31 2017-02-15 京博农化科技股份有限公司 一种茚虫威中间体的制备方法

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
See also references of EP3804853A4 *

Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN111747850A (zh) * 2020-08-06 2020-10-09 山东京博生物科技有限公司 一锅法合成5-氯-1-氧代-2，3-二氢-1h-茚-2-羧酸甲酯的方法
CN111747850B (zh) * 2020-08-06 2022-12-06 山东京博生物科技有限公司 一锅法合成5-氯-1-氧代-2，3-二氢-1h-茚-2-羧酸甲酯的方法
CN114671749A (zh) * 2022-04-01 2022-06-28 国科广化韶关新材料研究院 一种含锆环保型聚氨酯催化剂的制备方法及其应用

Also Published As

Publication number Publication date
US20210171476A1 (en) 2021-06-10
CN109701655A (zh) 2019-05-03
EP3804853A1 (en) 2021-04-14
EP3804853A4 (en) 2021-08-04
US11639336B2 (en) 2023-05-02
EP3804853B1 (en) 2022-03-23
CN109701655B (zh) 2019-11-19

Similar Documents

Publication Publication Date Title
WO2019233209A1 (zh) 一种s体茚虫威的制备方法
CN107406411B (zh) (r,s)-烟碱的制备方法
Sato et al. Csp3–Csp3 homocoupling reaction of benzyl halides catalyzed by rhodium
DE112006001798B4 (de) Übergangsmetallkomplexe und diese enthaltende Katalysatorzusammensetzungen
WO2019233211A1 (zh) 一种高光学茚虫威中间体的制备方法
Matharu et al. Asymmetric Transfer Hydrogenation of C O and C N Bonds by Tethered RhIII Catalysts
JP2000514436A (ja) 官能化されたフェロセニルジホスフィン類、その製造法、及びその用途
Paley Enantiomerically pure planar chiral organometallic complexes via facially selective π-complexation
DE60208305T2 (de) Verfahren zur Herstellung von optisch-aktiven Aminalkoholen
US20230151035A1 (en) Preparation method for and application of chiral spirocyclic phosphine-nitrogen-phosphine tridentate ligand and iridium catalyst thereof
CN110511217B (zh) 一种催化茚虫威关键中间体合成的催化剂及其应用
US7256311B2 (en) Process for hydrogenating unactivated imines using ruthenium complexes as catalysts
CN104803871A (zh) 一种制备普瑞巴林中间体的方法
Bastin et al. Enantioselective alkylation of benzaldehyde with diethylzinc catalyzed by 1, 1′-and 1, 2-disubstituted ferrocenyl amino alcohols
CN106256816B (zh) 一种α,β-不饱和羰基化合物的E-异构体制备Z-异构体的方法
Ho et al. Tandem [1, 2]‐Wittig Rearrangement/Lactonization of γ‐Benzyloxy Vinylogous Urethanes: Application to the Synthetic Studies of Maculalactone A, Planchol C and γ‐Lycorane
CN101519374B (zh) 一种手性吡啶类芳环氨基醇的衍生物的合成方法及其部分中间产物与最终产物
CN107382813B (zh) 格列美脲关键中间体的合成方法
CN103709072B (zh) 一种光活性三氟甲基胺类化合物及其制备方法
DE19915602A1 (de) 3-Amino-4-arylpropan-1-ol-Derivate, deren Herstellung und Verwendung
JP2003513117A (ja) オレフィンの重合用触媒
US6919292B2 (en) Transition metal compound, coordinative compound, catalyst for polymerization of olefin, and process for polymerization of olefin using the catalyst
CN114790189B (zh) 瑞卢戈利中间体的制备方法
CN102698798A (zh) 一种多孔铁基催化剂及其应用
KR102434452B1 (ko) 가교제 화합물의 제조 방법

Legal Events

Date Code Title Description
121 Ep: the epo has been informed by wipo that ep was designated in this application

Ref document number: 19815254

Country of ref document: EP

Kind code of ref document: A1

NENP Non-entry into the national phase

Ref country code: DE

ENP Entry into the national phase

Ref document number: 2019815254

Country of ref document: EP

Effective date: 20210111