Preparation method of isoxazole compound and isoxazole compound intermediate

A compound and isoxazole technology, applied in the field of organic synthesis, can solve the problems of dangerous post-processing process, many impurities and high cost, and achieve the effects of avoiding safety and three waste problems, high product purity and low cost

Active Publication Date: 2016-06-29
ZHEJIANG ZHUJI UNITED CHEM
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

This preparation method not only has low yield and many impurities, but also the use of highly toxic cyanide reagents leads to dangerous post-treatment process, high cost and many wastes.

Method used

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  • Preparation method of isoxazole compound and isoxazole compound intermediate
  • Preparation method of isoxazole compound and isoxazole compound intermediate
  • Preparation method of isoxazole compound and isoxazole compound intermediate

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preparation example Construction

[0035] A preparation method of isoxazole compounds, comprising the steps of:

[0036] Step A, in a solvent and in the presence of a base, compound (I) reacts with compound (II) at a certain temperature, and then continues to react with an oxidant to obtain an intermediate compound (III);

[0037] Step B, compound (III) reacts with an acid chloride reagent, and then reacts with alcohol at a certain temperature to obtain compound (IV), or reacts compound (III) with an alkylating agent at a certain temperature under the action of a base to obtain compound ( IV);

[0038] Step C, in a solvent, compound (IV) reacts with sulfide (V) at a certain temperature to obtain compound (VI);

[0039] Step D, in a solvent and in the presence of a base, compound (VI) and methyl ketone (VII) are condensed at a certain temperature to obtain compound (VIII);

[0040] Step E, in a solvent, after compound (VIII) and orthoformate (IX) and acid anhydride carry out ene etherification reaction at a ce...

Embodiment 1

[0060] Embodiment 1: the preparation of 4-chloro-3-nitrobenzotrifluoride

[0061] In a 1000mL three-necked flask, add 400g of p-chlorobenzotrifluoride, add a mixed acid of 273g of 98% sulfuric acid and 190g of 98% nitric acid dropwise at 30°C, continue to react for 4 hours after the dropwise addition, separate the organic layer, and wash the organic layer twice , to obtain 480g of 4-chloro-3-nitrobenzotrifluoride.

Embodiment 2

[0062] Embodiment 2: Preparation of 2-nitro-4-trifluoromethylbenzoic acid

[0063] In a 1000mL three-necked flask equipped with a thermometer, add 500g of DMF, 180g of potassium carbonate, and 78g of ethyl cyanoacetate. 150 g of 4-chloro-3-nitrobenzotrifluoride was added, and the temperature of the reactant was controlled within 50°C. After the dropwise addition, the reaction was continued to stir for 1 hour. Add 230g35%H dropwise 2 o 2 After the dropwise addition was completed, the reaction was continued for 2 hours, hydrogen peroxide was quenched, solvent removal was added, water was added, acidified with hydrochloric acid, filtered, washed with water, and dried to obtain 149g of 2-nitro-4-trifluoromethylbenzoic acid. 1 H-NMRδppm (DMSO-d 6 ): 14.39 (br, 1H), 8.46 (s, 1H), 8.21 (d, J=8.0Hz, 1H), 8.09 (d, J=8.0Hz, 1H).

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Abstract

The present invention discloses a preparation method of an isoxazole compound and an isoxazole compound intermediate. According to the method, an intermediate acid (III) is prepared by substitution reaction of a compound (I) as a raw material and a compound (II) in the presence of a base and then oxidation reaction; an intermediate (IV) is prepared by methyl esterification of the intermediate acid (III); an intermediate (VI) is prepared by thionation of the intermediate (IV); an intermediate (VIII) is prepared by condensation of the intermediate (VI) and cyclopropyl methyl ketone under basic conditions; an intermediate (X) is prepared by ene-etherification reaction of the intermediate (VIII) and ortho-formate and then cyclization with hydroxylamine hydrochloride; and the isoxazole compound (XI) is prepared by oxidation of methylthio groups of the intermediate (X) by hydrogen peroxide. Raw materials are readily available, yield is high, purity is high, three-waste is low, cost is low, and the preparation method has good industrial value.

Description

technical field [0001] The invention belongs to the field of organic synthesis, and in particular relates to a synthesis method of isoxazole compounds and intermediates thereof. Background technique [0002] Isoxazole compounds are an important class of organic compounds, which are widely used in the fields of medicine and pesticides. For example, isoxaflutole, a new herbicide developed by Bayer, is widely used in corn and sugarcane fields to control gramineous weeds and broadleaf weeds. CN1069267, CN1057524, CN1135210 disclose the preparation method of isoxaflutole, its synthesis process is to use 2-nitro-4-trifluoromethylbenzoic acid (a) as raw material, obtain 2-nitro- Methyl 4-trifluoromethylbenzoate (b), intermediate (b) reacts with sodium methylthiolate to obtain 2-methylthio-4-trifluoromethylbenzoic acid methyl ester (c), intermediate (c ) and cyclopropyl ketone are condensed under alkaline conditions to obtain 3-cyclopropyl-1-(2-methylthio-4-trifluoromethylphenyl) ...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07D261/08C07C205/58C07C201/12C07C323/62C07C319/14
CPCC07C201/12C07C205/58C07C319/14C07C323/62C07D261/08
Inventor 苏叶华史界平陆建鑫张天浩蔡国平虞小华陈邦池
Owner ZHEJIANG ZHUJI UNITED CHEM
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