WO2018023980A1 - 丙硫菌唑中间体1-氯-1-乙酰基环丙烷的合成方法 - Google Patents

丙硫菌唑中间体1-氯-1-乙酰基环丙烷的合成方法 Download PDF

Info

Publication number
WO2018023980A1
WO2018023980A1 PCT/CN2017/077663 CN2017077663W WO2018023980A1 WO 2018023980 A1 WO2018023980 A1 WO 2018023980A1 CN 2017077663 W CN2017077663 W CN 2017077663W WO 2018023980 A1 WO2018023980 A1 WO 2018023980A1
Authority
WO
WIPO (PCT)
Prior art keywords
chloro
reaction
oxobutyrate
haloethyl
sulfonate
Prior art date
Application number
PCT/CN2017/077663
Other languages
English (en)
French (fr)
Inventor
陈国云
罗治斌
谢吉民
王晨
刘润兴
Original Assignee
扬州天辰精细化工有限公司
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 扬州天辰精细化工有限公司 filed Critical 扬州天辰精细化工有限公司
Publication of WO2018023980A1 publication Critical patent/WO2018023980A1/zh

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C45/00—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds
    • C07C45/61—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups
    • C07C45/67—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups by isomerisation; by change of size of the carbon skeleton
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C45/00—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds
    • C07C45/61—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups
    • C07C45/67—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups by isomerisation; by change of size of the carbon skeleton
    • C07C45/673—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups by isomerisation; by change of size of the carbon skeleton by change of size of the carbon skeleton
    • C07C45/676—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups by isomerisation; by change of size of the carbon skeleton by change of size of the carbon skeleton by elimination of carboxyl groups
    • 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
    • C07C67/307—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 halogen; by substitution of halogen atoms by other halogen atoms
    • 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
    • C07C67/333—Preparation of carboxylic acid esters by modifying the acid moiety of the ester, such modification not being an introduction of an ester group by isomerisation; by change of size of the carbon skeleton
    • C07C67/343—Preparation of carboxylic acid esters by modifying the acid moiety of the ester, such modification not being an introduction of an ester group by isomerisation; by change of size of the carbon skeleton by increase in the number of carbon atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C49/00—Ketones; Ketenes; Dimeric ketenes; Ketonic chelates
    • C07C49/29—Saturated compounds containing keto groups bound to rings
    • C07C49/327—Saturated compounds containing keto groups bound to rings containing halogen

Definitions

  • the invention relates to the technical field of chemical production, in particular to a new industrial synthesis method of 1-chloro-1-acetylcyclopropane.
  • Prothioconazole (common name: prothioconazole) is a novel broad-spectrum triazole thione fungicide. Prothioconazole is mainly used to control many diseases such as wheat, barley, rape, peanut, rice and bean crops. It has good control effects on all wheat diseases, such as powdery mildew, sheath blight, blight, leaf spot, rust, sclerotinia, net blotch, and moiré in wheat and barley. It can also control soil-borne diseases such as sclerotinia sclerotiorum and main foliar diseases such as gray mold, black spot, brown spot, black smut, sclerotinia and rust, etc.
  • Prothioconazole not only has good safety to crops, but also has good anti-disease and curative effect, and it has obvious yield increase. Compared with triazole fungicides, prothioconazole has a broader spectrum of sterilization.
  • prothioconazole There are several routes for the synthesis of prothioconazole, which are obtained by multi-step reaction of 1-chlorocyclopropionyl chloride and 1-chloro-1-acetylcyclopropane as main raw materials. Among them, 1-chloro-1-acetylcyclopropane is stable in nature and the price is more reasonable. Therefore, most of the production processes use 1-chloro-1-acetylcyclopropane as a starting material to prepare prothioconazole.
  • the typical synthetic route is as follows:
  • the object of the present invention is to provide a novel synthetic method suitable for industrial production of 1-chloro-1-acetylcyclopropane, a key intermediate of prothioconazole.
  • R is an alkyl group of 1 to 4 carbons, or a phenyl group, or a benzyl group;
  • X is a halogen, or a p-toluenesulfonyloxy group (OTs), or a methanesulfonyloxy group (OMs).
  • Compound (2) 2-(2-haloethyl)-3-oxobutyrate or 2-(2-sulfonateethyl)-3-oxobutyrate.
  • Compound (3) 2-(2-haloethyl)-2-chloro-3-oxobutanoate or 2-(2-sulfonateethyl)-2-chloro-3-oxobutyl Acid ester.
  • the invention optimizes the production process of the existing 1-chloro-1-acetylcyclopropane, reduces the three wastes, is safe, reliable, high efficiency, high reaction yield, low cost, and is a high quality 1-chloro-1-acetyl A method for synthesizing a cyclopropane.
  • the halogen is chlorine or bromine, and from the viewpoint of cost, the chlorine is optimally selected.
  • the temperature condition of the monoalkylation reaction is 40 to 60 ° C, and the side reaction is the least.
  • step 1) a single alkylation reaction is carried out under the protection of nitrogen with acetone as a solvent, sodium iodide, potassium iodide or tetrabutylammonium iodide as a catalyst, and potassium carbonate or sodium carbonate as an alkali raw material.
  • the charge ratio of the 1,2-dihaloalkane to the alkyl acetoacetate is from 3 to 5:1, and the excess 1,2-dihaloalkane can reduce the formation of by-products: in addition, the excess The 1,2-dihaloalkane can be recycled.
  • the temperature condition of the chlorination reaction is -10 to 10 °C.
  • step 2) 2-(2-haloethyl)-3-oxobutyrate or 2-(2-sulfonateethyl)-3-oxobutyrate is first dissolved in In dichloromethane, sulfonyl chloride is added dropwise to carry out chlorination reaction. After completion of the reaction, ice water is added, and the organic layer is obtained after stirring, and then washed with brine and dried to obtain 2-(2-haloethyl)-2-chloro 3-oxobutyrate or 2-(2-sulfonateethyl)-2-chloro-3-oxobutanoate.
  • the temperature condition of the hydrolysis reaction is 100 to 110 °C.
  • step 3 2-(2-haloethyl)-2-chloro-3-oxobutyrate or 2-(2-sulfonateethyl)-2-chloro-3 is first introduced.
  • - Oxybutyrate is dissolved in glacial acetic acid, and then concentrated hydrochloric acid solution is added to carry out hydrolysis reaction.
  • glacial acetic acid is distilled off, and the residue is extracted with tert-butyl methyl ether to obtain an organic phase, which is washed successively with brine, dried and concentrated. Distillation under reduced pressure gave 3,5-dichloropentan-2-one or 3-chloro-4-sulfonate pentan-2-one.
  • the temperature condition of the ring closure reaction is 80 to 100 °C.
  • the lye is an aqueous solution of sodium hydroxide or an aqueous solution of potassium hydroxide;
  • the quaternary ammonium salt is tetrabutylammonium chloride, tetrabutylammonium bromide or dodecyltrimethyl chloride. Ammonium, as well as other similar phase transfer catalysts or crown ether catalysts.
  • the lye is an aqueous solution of sodium hydroxide; and the quaternary ammonium salt is tetrabutylammonium bromide.
  • the invention has the advantages that the raw materials of the reaction are cheap and easy to obtain, and the solvent used is easy to recycle and apply.
  • the reaction yield of each step is high and the operation is simple, and it is suitable for industrial production.

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)

Abstract

丙硫菌唑中间体1-氯-1-乙酰基环丙烷的合成方法，涉及化工生产技术领域，将乙酰乙酸烷基酯和1,2-二卤代烷或乙二醇二磺酸酯混合进行单烷基化反应，再经氯化反应后，再与强酸混合进行水解，取得3,5-二氯戊烷-2-酮或3-氯-4-磺酸酯基戊烷-2-酮；最后以季铵盐为催化剂，将3,5-二氯戊烷-2-酮或3-氯-4-磺酸酯基戊烷-2-酮和碱液混合进行关环反应，取得1-氯-1-乙酰基环丙烷。本发明降低了成本，减少三废，安全可靠，反应收率高。

Description

丙硫菌唑中间体1-氯-1-乙酰基环丙烷的合成方法 技术领域
本发明涉及化工生产技术领域，具体涉及1-氯-1-乙酰基环丙烷的新产业化合成方法。
背景技术
丙硫菌唑(通用名称：prothioconazole)是一种新型广谱三唑硫酮类杀菌剂。丙硫菌唑主要用于防治禾谷类作物如小麦、大麦、油菜、花生、水稻和豆类作物等众多病害。儿乎对所有麦类病害都有很好的防治效果，如小麦和大麦的白粉病、纹枯病、枯萎病、叶斑病、锈病、菌核病、网斑病、云纹病等。还能防治油莱和花生的土传病害，如菌核病，以及主要叶面病害，如灰霉病、黑斑病、褐斑病、黑胫病、菌核病和锈病等，不仅具有很好的内吸活性，优异的保护、治疗和铲除活性，且持效期长。丙硫菌唑对作物不仅具有良好的安全性，防病治病效果好，而且增产明显，同三唑类杀茵剂相比，丙硫菌唑具有更广谱的杀菌活住。
丙硫菌唑的合成主要有几条工艺路线，分别由1-氯环丙甲酰氯和1-氯-1-乙酰基环丙烷为主要原料经多步反应得到产品。其中1-氯-1-乙酰基环丙烷性质稳定，且价格更为合理，因此大部分生产工艺均以1-氯-1-乙酰基环丙烷作为起始原料制备丙硫菌唑。典型的合成路线见下式：
Figure PCTCN2017077663-appb-000001
其中起始原料1-氯-1-乙酰基环丙烷的合成对丙硫菌唑的合成有着重要的意义。
目前1-氯-1-乙酰基环丙烷的合成工艺采取的是以丁内酯为原料的方案，如下式：
Figure PCTCN2017077663-appb-000002
此路线中乙醇钠和丁内酯价格较高，且在第一步反应用到，导致了整个成本偏高。
发明内容
发明目的是提供丙硫菌唑关键中间体1-氯-1-乙酰基环丙烷新的、适合产业化生产的合成方法。
本发明合成技术方案包括以下步骤：
1)将乙酰乙酸烷基酯和过量1,2-二卤代烷或乙二醇二磺酸酯混合，在反应体系的温度为40～60℃的条件下进行单烷基化反应，取得2-(2-卤代乙基)-3-氧代丁酸酯或2-(2-磺酸酯基乙基)-3-氧代丁酸酯；
2)将2-(2-卤代乙基)-3-氧代丁酸酯或2-(2-磺酸酯基乙基)-3-氧代丁酸酯与氯气或磺酰氯混合，在反应体系的温度为-10～10℃的条件下进行氯化反应，取得2-(2-卤代乙基)-2-氯-3-氧代丁酸酯或2-(2-磺酸酯基乙基)-2-氯-3-氧代丁酸酯；
3)将2-(2-卤代乙基)-2-氯-3-氧代丁酸酯或2-(2-磺酸酯基乙基)-2-氯-3-氧代丁酸酯和强酸混合，在反应体系的温度为100～110℃的条件下进行水解，取得3,5-二氯戊烷-2-酮或3-氯-4-磺酸酯基戊烷-2-酮；
4)以季铵盐为催化剂，将3,5-二氯戊烷-2-酮或3-氯-4-磺酸酯基戊烷-2-酮和碱液混合，在反应体系的温度为80～100℃的条件下进行关环反应，取得1-氯-1-乙酰基环丙烷。
以上化学反应式如下：
Figure PCTCN2017077663-appb-000003
以上各分子结构式中，R为1-4个碳的烷基，或苯基，或苄基；X为卤素，或对甲苯磺酰氧基(OTs)，或甲磺酰氧基(OMs)。
以上化学反应式中各化合物说明：
化合物(1)：乙酰乙酸烷基酯。
化合物(2)：2-(2-卤代乙基)-3-氧代丁酸酯或2-(2-磺酸酯基乙基)-3-氧代丁酸酯。
化合物(3)：2-(2-卤代乙基)-2-氯-3-氧代丁酸酯或2-(2-磺酸酯基乙基)-2-氯-3-氧代丁酸酯。
化合物(4)：3,5-二氯戊烷-2-酮或3-氯-4-磺酸酯基戊烷-2-酮。
化合物(5)：1-氯-1-乙酰基环丙烷。
本发明优化了现有1-氯-1-乙酰基环丙烷的生产工艺，减少三废，安全可靠，高效率，高反应收率，成本低，是一种高质量的1-氯-1-乙酰基环丙烷的合成方法。
进一步地，本发明所述步骤1)中，所述卤素为氯或溴，从成本角度考虑，最优选择为氯。
所述步骤1)中，所述单烷基化反应的温度条件为40～60℃，副反应最少。
所述步骤1)中，以丙酮为溶剂，以碘化钠，碘化钾或者四丁基碘化铵为催化剂，以碳酸钾或碳酸钠为碱原料，在氮气保护下进行单烷基化反应。
所述步骤1)中，所述1,2-二卤代烷与乙酰乙酸烷基酯的投料质量比为3～5∶1，过量的1,2-二卤代烷可以减少副产物的生成：另外，过量的1,2-二卤代烷可以回收套用。
本发明所述步骤2)中，所述氯化反应的温度条件为-10～10℃。
所述步骤2)中，先将2-(2-卤代乙基)-3-氧代丁酸酯或2-(2-磺酸酯基乙基)-3-氧代丁酸酯溶解于二氯甲烷中，再滴加磺酰氯进行氯化反应，反应完成后加入冰水，搅拌后取得有机层，再用盐水洗涤、干燥，取得2-(2-卤代乙基)-2-氯-3-氧代丁酸酯或2-(2-磺酸酯基乙基)-2-氯-3-氧代丁酸酯。
所述步骤3)中，所述水解反应的温度条件为100～110℃。
所述步骤3)中，先将2-(2-卤代乙基)-2-氯-3-氧代丁酸酯或2-(2-磺酸酯基乙基)-2-氯-3-氧代丁酸酯溶解于冰醋酸中，再加入浓盐酸溶液进行水解反应，反应结束后蒸馏回收冰醋酸，残余物用叔丁基甲基醚提取取得有机相，再依次经盐水洗涤、干燥、浓缩、减压蒸馏，取得3,5-二氯戊烷-2-酮或3-氯-4-磺酸酯基戊烷-2-酮。
所述步骤4)中，所述关环反应的温度条件为80～100℃。
先将3,5-二氯戊烷-2-酮或3-氯-4-磺酸酯基戊烷-2-酮溶于甲苯 中，再加入碱液、季铵盐，在反应体系的温度为80～100℃的条件进行关环反应，反应结束取有机相，再用盐水洗涤、硫酸钠干燥后，经精馏柱减压蒸馏回收甲苯，残余物继续减压精馏得到化合物(5)——1-氯-1-乙酰基环丙烷。
所述步骤4)中，所述碱液为氢氧化钠水溶液或氢氧化钾水溶液；所述季铵盐为四丁基氯化铵、四丁基溴化铵或十二烷基三甲基氯化铵，以及其他类似作用的相转移催化剂或者冠醚催化剂。
优选的所述碱液为氢氧化钠水溶液；所述季铵盐为四丁基溴化铵。
本发明的有益之处在于，反应的原料便宜易得，所用溶剂均易回收套用。各步反应收率高且操作简便，适宜于工业化生产。
具体实施方式
一、生产工艺：
1、中间体化合物(2)的合成：
在三口圆底烧瓶中加入化合物(1)(223.5g，1.72mol)和丙酮(1100毫升)，加入固体碘化钠(12.9g，0.086mol)，1,2-二氯乙烷(681g，8.88mol)及无水碳酸钾(285g，2.06mol)，氮气保护下升温到55℃，保持微沸回流状态搅拌24小时，气相检测反应，化合物(1)的转化率大于96％，浓缩回收溶剂丙酮及二氯乙烷，残余物用叔丁基甲基醚提取，过滤，洗涤固体，滤液用盐水洗涤，干燥后浓缩，高真空减压蒸馏得化合物(2)265g，气相纯度大于97％，产率80％。
2、中间体化合物(3)的合成：
在三口圆底烧瓶中加入化合物(2)(250克，1.3mol)及二氯甲烷(1250毫升)，降温到0℃，开启搅拌，滴加磺酰氯(193克，1.43mol)，控制体系温度-10到10℃之间，1～2小时滴加完毕，滴完保温搅拌1h，GC中控原料全部反应完，加入500毫升冰水，搅拌30分钟，分去水层，有机层再用盐水洗涤2次，硫酸钠干燥后浓缩回收二氯甲烷，残余物减压蒸馏得无色液体产品274g，气相纯度大于95％，收率93％。
3、中间体化合物(4)的合成：
在三口圆底烧瓶中加入化合物(3)(250g，1.1mol)，1000毫升冰醋酸，以及36％的浓盐酸(335g，3.3mol)，加热到100-110度，保温反应8小时，GC检测原料反应完全，加上精馏柱减压蒸馏回收冰醋酸套用到下一批反应，残余物用叔丁基甲基醚提取，有机相盐水洗涤，硫酸钠干燥后浓缩，减压蒸馏得到产品化合物(4)155g，气相纯度大于97％，收率91％。
4、1-氯-1-乙酰基环丙烷(5)的合成：
在三口圆底烧瓶中加入化合物(4)(140g，0.9mol)，700毫升甲苯，以及40％的氢氧化钠或氢氧化钾溶液(99g，0.99mol)，再加入四丁基溴化铵固体(14.5g，0.045mol)加热到80～100℃，保温反应24小时，GC检测原料反应完全，分去水层，有机相再用盐水洗涤，硫酸钠干燥，加上精馏柱减压蒸馏回收甲苯，残余物继续减压精馏，收集70～72℃/120mmHg馏分得到无色透明 液体产品化合物(5)87.5g，气相纯度大于98％，收率82％。1H NMR(400MHz,CDCl3)δ1.36-1.62(m,4H),2.46(s,3H)。

Claims (9)

  1. 丙硫菌唑中间体1-氯-1-乙酰基环丙烷的合成方法，其特征在于包括以下步骤：
    1)将乙酰乙酸烷基酯和过量1,2-二卤代烷或乙二醇二磺酸酯混合，在反应体系的温度为40～60℃的条件下进行单烷基化反应，取得2-(2-卤代乙基)-3-氧代丁酸酯或2-(2-磺酸酯基乙基)-3-氧代丁酸酯；
    2)将2-(2-卤代乙基)-3-氧代丁酸酯或2-(2-磺酸酯基乙基)-3-氧代丁酸酯与氯气或磺酰氯混合，在反应体系的温度为-10～10℃的条件下进行氯化反应，取得2-(2-卤代乙基)-2-氯-3-氧代丁酸酯或2-(2-磺酸酯基乙基)-2-氯-3-氧代丁酸酯；
    3)将2-(2-卤代乙基)-2-氯-3-氧代丁酸酯或2-(2-磺酸酯基乙基)-2-氯-3-氧代丁酸酯和强酸混合，在反应体系的温度为100～110℃的条件下进行水解，取得3,5-二氯戊烷-2-酮或3-氯-4-磺酸酯基戊烷-2-酮；
    4)以季铵盐为催化剂，将3,5-二氯戊烷-2-酮或3-氯-4-磺酸酯基戊烷-2-酮和碱液混合，在反应体系的温度为80～100℃的条件下进行关环反应，取得1-氯-1-乙酰基环丙烷。
  2. 根据权利要求1所述的合成方法，其特征在于所述步骤1)中，所述卤素为氯或溴。
  3. 根据权利要求1所述的合成方法，其特征在于所述步骤1)中，以丙酮为溶剂，以碘化钠，碘化钾或者四丁基碘化铵为催化剂，以碳 酸钾或碳酸钠为碱原料，在氮气保护下进行单烷基化反应。
  4. 根据权利要求1或2或3所述的合成方法，其特征在于所述步骤1)中，所述1,2-二卤代烷与乙酰乙酸烷基酯的投料质量比为3～5∶1。
  5. 根据权利要求1所述的合成方法，其特征在于所述步骤2)中，先将2-(2-卤代乙基)-3-氧代丁酸酯或2-(2-磺酸酯基乙基)-3-氧代丁酸酯溶解于二氯甲烷中，再滴加磺酰氯进行氯化反应，反应完成后加入冰水，搅拌后取得有机层，再用盐水洗涤、干燥，取得2-(2-卤代乙基)-2-氯-3-氧代丁酸酯或2-(2-磺酸酯基乙基)-2-氯-3-氧代丁酸酯。
  6. 根据权利要求1所述的合成方法，其特征在于所述步骤3)中，先将2-(2-卤代乙基)-2-氯-3-氧代丁酸酯或2-(2-磺酸酯基乙基)-2-氯-3-氧代丁酸酯溶解于冰醋酸中，再加入浓盐酸溶液进行水解反应，反应结束后蒸馏回收冰醋酸，残余物用叔丁基甲基醚提取取得有机相，再依次经盐水洗涤、干燥、浓缩、减压蒸馏，取得3,5-二氯戊烷-2-酮或3-氯-4-磺酸酯基戊烷-2-酮。
  7. 根据权利要求1所述的合成方法，其特征在于所述步骤4)中，先将3,5-二氯戊烷-2-酮或3-氯-4-磺酸酯基戊烷-2-酮溶于甲苯中，再加入碱液、季铵盐，在反应体系的温度为80～100℃的条件进行关环反应，反应结束取有机相，再用盐水洗涤、硫酸钠干燥后，经精馏柱减压蒸馏回收甲苯，残余物继续减压精馏得到1-氯-1-乙酰基环丙烷。
  8. 根据权利要求1所述的合成方法，所述步骤4)中，所述碱液为氢氧化钠水溶液或氢氧化钾水溶液；所述季铵盐为四丁基氯化铵、四丁基溴化铵或十二烷基三甲基氯化铵。
  9. 根据权利要求1所述的合成方法，所述步骤4)中，所述碱液为氢氧化钠水溶液；所述季铵盐为四丁基溴化铵。
PCT/CN2017/077663 2016-08-05 2017-03-22 丙硫菌唑中间体1-氯-1-乙酰基环丙烷的合成方法 WO2018023980A1 (zh)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
CN201610632705.4A CN106278850B (zh) 2016-08-05 2016-08-05 丙硫菌唑中间体1-氯-1-乙酰基环丙烷的合成方法
CN201610632705.4 2016-08-05

Publications (1)

Publication Number Publication Date
WO2018023980A1 true WO2018023980A1 (zh) 2018-02-08

Family

ID=57665408

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/CN2017/077663 WO2018023980A1 (zh) 2016-08-05 2017-03-22 丙硫菌唑中间体1-氯-1-乙酰基环丙烷的合成方法

Country Status (2)

Country Link
CN (1) CN106278850B (zh)
WO (1) WO2018023980A1 (zh)

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN115594651A (zh) * 2022-10-25 2023-01-13 宁夏一帆生物科技有限公司（Cn） 一种3-乙酰基-3-氯二氢呋喃-2(3h)-酮的合成方法

Families Citing this family (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN106278850B (zh) * 2016-08-05 2018-10-16 扬州天辰精细化工有限公司 丙硫菌唑中间体1-氯-1-乙酰基环丙烷的合成方法
CN107473948B (zh) * 2017-09-26 2020-07-14 安徽国星生物化学有限公司 一种由乙酰乙酸乙酯制备3,5-二氯-2-戊酮的合成方法
CN108440267A (zh) * 2018-03-29 2018-08-24 连云港市金囤农化有限公司 1-氯-1-乙酰基环丙烷的合成方法
CN110627627A (zh) * 2019-09-20 2019-12-31 江苏澄扬作物科技有限公司 1-（1-氯环丙基）-2-（2-氯苯基）乙酮的制备方法及其中间体
CN111205176B (zh) * 2020-01-14 2022-06-14 大连九信精细化工有限公司 一种3,5-二卤代-2-戊酮的合成方法
CN112794849B (zh) * 2020-12-31 2022-05-31 重庆医科大学 3-(2-氯乙基)-2-甲基-4H-吡啶并[1,2-a]嘧啶-4-酮的合成方法
CN115010587B (zh) * 2022-07-15 2024-04-30 辽宁众辉生物科技有限公司 一种清洁的1-乙酰基-1-氯环丙烷合成方法
CN117105759B (zh) * 2023-10-24 2024-02-02 江苏七洲绿色化工股份有限公司 一种连续制备2-氯-1-（1-氯环丙基）乙酮的方法

Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US2497483A (en) * 1948-12-14 1950-02-14 Us Rubber Co 1-acetyl-2-methyl-2-chloromethylcyclopropane
US5079374A (en) * 1987-07-10 1992-01-07 Bayer Aktiengesellschaft Fungicidal and plant growth-regulating hydroxyalkyl-azolyl derivatives
CN103709023A (zh) * 2013-12-24 2014-04-09 秦永其 3,5-二氯-2-戊酮的合成方法
CN104292089A (zh) * 2014-09-30 2015-01-21 大连九信生物化工科技有限公司 一种1-氯-1’-氯乙酰基环丙烷的合成工艺
CN106278850A (zh) * 2016-08-05 2017-01-04 扬州天辰精细化工有限公司 丙硫菌唑中间体1‑氯‑1‑乙酰基环丙烷的合成方法

Family Cites Families (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE4206917A1 (de) * 1992-03-05 1993-09-09 Bayer Ag Verfahren zur herstellung von 1-fluorcyclopropyl-methyl-keton

Patent Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US2497483A (en) * 1948-12-14 1950-02-14 Us Rubber Co 1-acetyl-2-methyl-2-chloromethylcyclopropane
US5079374A (en) * 1987-07-10 1992-01-07 Bayer Aktiengesellschaft Fungicidal and plant growth-regulating hydroxyalkyl-azolyl derivatives
CN103709023A (zh) * 2013-12-24 2014-04-09 秦永其 3,5-二氯-2-戊酮的合成方法
CN104292089A (zh) * 2014-09-30 2015-01-21 大连九信生物化工科技有限公司 一种1-氯-1’-氯乙酰基环丙烷的合成工艺
CN106278850A (zh) * 2016-08-05 2017-01-04 扬州天辰精细化工有限公司 丙硫菌唑中间体1‑氯‑1‑乙酰基环丙烷的合成方法

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN115594651A (zh) * 2022-10-25 2023-01-13 宁夏一帆生物科技有限公司（Cn） 一种3-乙酰基-3-氯二氢呋喃-2(3h)-酮的合成方法

Also Published As

Publication number Publication date
CN106278850A (zh) 2017-01-04
CN106278850B (zh) 2018-10-16

Similar Documents

Publication Publication Date Title
WO2018023980A1 (zh) 丙硫菌唑中间体1-氯-1-乙酰基环丙烷的合成方法
WO2020147861A1 (zh) 一种β-三氟甲基酰胺类化合物的电化学制备方法
DK3215481T3 (en) PROCEDURE FOR PREPARING BIPHENYLAMINES OF AZOBENZENES USING RUTHENIUM CATALYZE
CN111303051A (zh) 制5-(3,6-二氢-2,6-二氧-4-三氟甲基-1(2h)-嘧啶基)苯硫酚方法
CN113735701A (zh) 一种8-羟基-2,2,14,14-四甲基十五烷二酸的制备方法
CN109836350A (zh) 阿托伐他汀关键中间体的环保制备方法
CN107406374B (zh) 制备3-氯-2-乙烯基苯基磺酸酯的方法
WO2006080555A1 (ja) （ｚ）－１－フェニル－１－（ｎ，ｎ－ジエチルアミノカルボニル）－２－フタルイミドメチルシクロプロパンの製造方法
EP3577099B1 (en) A novel process for the synthesis of 1-aryl-1-trifluoromethylcyclopropanes
TW201607918A (zh) 用於製備４－［［（苯甲醯基）胺基］磺基］苯甲醯基氯化物之方法及醯基胺磺醯基苯甲醯胺之製備
JP3663229B2 (ja) ４−ハロ−２′−ニトロブチロフエノン化合物の製造方法
JP2023527071A (ja) （４－イソプロポキシ－２－メチル）フェニルイソプロピルケトンの調製法
JP7495881B2 (ja) ３，４－ジクロロ－ｎ－（２－シアノフェニル）－５－イソチアゾールカルボキサミドの製造方法
CN109503343B (zh) 一种光引发剂184的制备方法
CN113754612B (zh) 一种西地那非中间体的制备方法
CN106631867B (zh) 一种合成2-苯甲酰氨基-3-芳基丙烯酸酯的方法
NO20025652L (no) Fremgangsmåte for fremstilling av trifluoretoksysubstituerte benzosyrer
CN107074699B (zh) 用于制备5-溴-1,2,3-三氯苯的方法
WO2023082149A1 (en) Process and intermediates for preparation of isofetamid
CN110003111B (zh) 一种2-芳基-3-醚基-3-吡唑丙烯腈类化合物的制备方法
WO2022002117A1 (zh) 一种制备含异恶唑啉脲嘧啶类化合物中间体的方法
JP2008533099A (ja) ５−ハロ−２，４，６−トリフルオロイソフタル酸の製造方法
JP4608888B2 (ja) ２−シアノ−２−（４−テトラヒドロピラニル）酢酸エステルの製法
JP4171965B2 (ja) ４，４−ジフルオロ−３−ブテン−１−オール誘導体の製造法
CN116813508A (zh) 高选择性合成5-卤代-2-甲基苯甲酸的方法

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: 17836164

Country of ref document: EP

Kind code of ref document: A1

NENP Non-entry into the national phase

Ref country code: DE

122 Ep: pct application non-entry in european phase

Ref document number: 17836164

Country of ref document: EP

Kind code of ref document: A1

122 Ep: pct application non-entry in european phase

Ref document number: 17836164

Country of ref document: EP

Kind code of ref document: A1

32PN Ep: public notification in the ep bulletin as address of the adressee cannot be established

Free format text: NOTING OF LOSS OF RIGHTS PURSUANT TO RULE 112(1) EPC (EPO FORM 1205A DATED 22.08.2019)

122 Ep: pct application non-entry in european phase

Ref document number: 17836164

Country of ref document: EP

Kind code of ref document: A1