CN114380762A

CN114380762A - Isoxazoline hydrazide derivative and preparation method and application thereof

Info

Publication number: CN114380762A
Application number: CN202210075862.5A
Authority: CN
Inventors: 李亚辉; 宋宝安; 张文博; 师少杰; 魏文超
Original assignee: Guizhou University
Current assignee: Guizhou University
Priority date: 2022-01-23
Filing date: 2022-01-23
Publication date: 2022-04-22

Abstract

The invention relates to the field of chemical industry and pesticides, in particular to an isoxazoline-containing hydrazide derivative, and a preparation method and application thereof. The invention reports a method for preparing hydrazide by reacting isoxazoline ester with hydrazine hydrate and reacting with acyl chloride or aldehyde to prepare isoxazoline-containing hydrazide derivatives (structures shown in the formulas (I) and (II)) which have good insecticidal activity on spodoptera frugiperda. A pesticide or a salt thereof which is useful for controlling lepidopteran pests such as Spodoptera frugiperda which are harmful to crops such as corn and sorghum, and a pest control agent containing the same. The structure and the preparation process are simple, the bisazide insecticidal composition can be used as a good substitute for a bishydrazide insecticide, and the application prospect is wide.

Description

Isoxazoline hydrazide derivative and preparation method and application thereof

Technical Field

The invention relates to the field of chemical industry and pesticides, in particular to isoxazoline hydrazide derivatives, and a preparation method and application thereof.

Background

The pesticide is taken as an important agricultural production data all the time, and the development of agricultural civilization of human beings is powerfully promoted. Especially after the twentieth century, pesticides have played a great role in increasing crop yield, delaying the growth of the world hungry population, and controlling excessive reproduction of pests. Spodoptera frugiperda is native to the tropics and subtropical regions of America, is a recognized important agricultural pest in the world, can harm more than 300 plants, and has the characteristics of more generations in the year, long harm time and large loss. Migrating from Burma to China in 12 and 11 months in 2018, and spreading to 26 provinces (cities and autonomous regions) in 10 months in 2019. They mainly damage corn and other cereal crops, and can reduce corn yield by 20% -40%, and in severe cases, can reduce corn yield by more than 70%. The data display of the information center of Ministry of agriculture is influenced by potential moth disasters, and the corn production demand gap of China is expanding at present. If the effective prevention and treatment are not carried out, the food safety of China is seriously threatened. Chemical pesticides are the main way to control spodoptera frugiperda, but because of their strong reproductive capacity, spodoptera frugiperda has developed obvious resistance to a variety of pesticides. Research shows that the Spodoptera frugiperda has moderate to high level resistance genes to organophosphorus, carbamate, nicotine and diamide chemical insecticides due to unreasonable application; the field resistance to chlorpyrifos, methyl parathion, diazinon, meprobamate, dichlorvos and malathion is 12-271 times, p-flubendiamide (500 times), chlorantraniliprole (160 times) and p-spinetoram (14 times). At present, joint control and joint control are mainly carried out on Spodoptera frugiperda everywhere through the existing medicament, and few pesticide creations are carried out on Spodoptera frugiperda, so that the development of novel efficient low-risk pesticide without cross resistance with the existing pesticide is urgently needed to prevent the situation that no pesticide is available.

The hydrazide insecticide is different from natural ecdysone, can simulate the interaction of 20E and an ecdysone receptor complex to realize the function of the ecdysone, and has the characteristics of slight toxicity, even no toxicity and difficult generation of drug resistance. In view of the fact that Spodoptera frugiperda has generated higher-level resistance to organophosphorus, carbamate, nicotine and bisamide chemical insecticides, the development of efficient bishydrazide substitute medicaments has great significance. However, the traditional diacylhydrazine pesticide skeleton has the defect of slow effect, and how to develop a novel efficient and low-toxicity hydrazide pesticide is a problem to be solved by scientists. Isoxazolines are five-membered heterocycles containing nitrogen (N) and oxygen (O) atoms, which have abundant biological activities, but are often used in molecules such as pharmaceuticals and veterinary drugs. The patent intends to develop a synthetic method of isoxazoline hydrazide derivatives and apply the isoxazoline hydrazide derivatives in the control of agricultural pests.

In conclusion, the hydrazide pesticide can simulate ecdysone, can effectively control hemiptera, lepidoptera and other pests, and becomes a new hot point for developing pesticides. But also has the defect of slow response in the aspect of preventing and controlling Spodoptera frugiperda by the existing hydrazide pesticide.

Disclosure of Invention

In view of the above, the invention introduces an isoxazoline structure, develops a series of isoxazoline hydrazide derivatives through the reaction between ester and hydrazine hydrate, and shows good insecticidal activity on spodoptera frugiperda. Introduction of an isoxazoline unit into a hydrazide structure is expected to develop an agricultural pest control agent having a novel structure.

In order to achieve the above object, the present invention provides the following technical solutions:

in a first aspect, the present invention provides isoxazoline hydrazide derivatives having a structure represented by formula (I) or formula (II), or stereoisomers, or pharmaceutically acceptable salts, or solvates, or prodrug molecules thereof:

wherein:

r1, R2 or R3 are each independently selected from: halogen, cyano, nitro, cyanoalkyl, hydroxyalkyl, amino, formyl, halogen-free or halogen-containing alkyl, alkenyl, alkynyl, cycloalkyl, alkoxy, alkylthio, alkylcarbonyl, alkoxycarbonyl, alkylaminoalkyl or alkoxyalkyl, unsubstituted or substituted aryl, heteroaryl, arylalkyl or heteroarylalkyl;

r4 is selected from hydrogen, halogen, cyano, nitro, optionally substituted or unsubstituted alkyl;

r5 or R6 are independently selected from one or more of methyl or alkyl optionally substituted with halogen, alkoxy optionally substituted with unsubstituted, cyano, halogen, cycloalkyl optionally substituted with unsubstituted, aryl optionally substituted with unsubstituted, preferably R5 or R6 are independently selected from

Z is selected from O or S.

In some embodiments of the invention, the isoxazoline hydrazide derivative, or a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, or a solvate thereof, or a prodrug molecule thereof,

r1, R2 or R3 are independently selected from hydrogen, deuterium, halogen, nitro, hydroxy, amino, mercapto, methyl, ethyl, n-propyl, sec-propyl, n-butyl, sec-butyl, isobutyl, phenyl, benzyl, pyridyl, -CH2CH2CN, -CHNCH 3, -CH2CH2CH2CN, -CH2 CHNCH 3, -CHNCH 2CH3, -CH2CH2F, -CHFCH3, -CH2CH2CH2F, -CH2CHFCH3, -CHFCH2CH3, -CH2CH2Cl, -CHClCH3, -CH2CH2Cl, -CH2CHClCH3, -CHClCH2CH3, -CH2CH2Br, -CHBrCH3, -CH2CH2CH2Br, -CH2CHBrCH3 or-CHBrCH 2CH 3;

r4 is selected from hydrogen, halogen, nitro, cyano, methyl, ethyl, N-propyl, isopropyl, sec-propyl, N-butyl, sec-butyl, isobutyl, phenyl, benzyl, pyridyl, -CF3, -SCH3, -CF2CF3, -CH2OCH3, -CH2OCH2CF3, -CH2SCH3, -CH2S (O) CH3, -CH2SO2CH3, -CH2SCF3, -OCH3, -OCH2CH3, -OCHF2, -OCF3, -OCF2Br, -OCF2CHF2, -SCH3, -SCH2CH3, -SCF3, -N (CH3)2, -C O) CH3, -C (O) NH2 or-C (S) NH 2;

r5 or R6 are independently selected from the group consisting of methyl, ethyl, n-propyl, sec-propyl, n-butyl, sec-butyl, isobutyl, tert-butyl, methylcyclopropyl, phenyl, benzyl, pyridyl, pyrazolyl, pyrrolyl, furyl, thienyl, thiazolyl, benzopyranyl, pyridazine, pyrimidine, pyrazine, -CH2CH2CN, -CHNCH 3, -CH2CH2CH2CN, -CH2 CHNCH 3, -CHNCH 2CH3, -CH2CH2F, -CHFCH3, -CH2CH2CH2F, -CH2CHFCH3, -CHFCH2CH3, -CH2CH2Cl, -CHCl 3, -CH2CH2CH2Cl, -CH2CHClCH3, -CHClCH2CH3, -CH2CH2Br, -CHBrCH3, -CH2CH2CH2Br, -CH2CHBrCH3, -CHBrCH2CH3,

In some embodiments of the invention, the isoxazoline hydrazide derivatives, including but not limited to:

in a second aspect, the invention further provides a preparation method of the isoxazoline hydrazide derivative, or a stereoisomer, a pharmaceutically acceptable salt, a solvate or a prodrug molecule thereof, wherein the isoxazoline hydrazide derivative is prepared by using an isoxazoline ester and hydrazine hydrate as raw materials, and reacting the raw materials with acyl chloride or aldehyde.

In some embodiments of the invention, the derivatives are prepared by a process comprising:

preferably, further comprising:

preferably, further comprising:

further comprising:

preferably, further comprising:

preferably, further comprising:

in a third aspect, the present invention further provides a composition comprising the isoxazoline hydrazide derivative, or a stereoisomer, or a pharmaceutically acceptable salt, or a solvate thereof, or a prodrug molecule thereof, or the isoxazoline hydrazide derivative prepared by the preparation method, or a stereoisomer, or a pharmaceutically acceptable salt, or a solvate thereof, or a prodrug molecule thereof, and any other effective ingredients.

In some embodiments of the invention, the composition includes, but is not limited to, a pesticide.

In a fourth aspect, the invention also provides a preparation comprising the composition and acceptable auxiliary materials or auxiliary agents.

In some embodiments of the invention, the formulation comprises one or more of Emulsifiable Concentrate (EC), Dust (DP), Wettable Powder (WP), Granules (GR), Aqueous Solution (AS), Suspension Concentrate (SC), ultra low volume spray (ULV), Soluble Powder (SP), Microcapsules (MC), smoke (FU), aqueous Emulsion (EW), water dispersible granules (WG).

In a fifth aspect, the invention further provides the isoxazoline hydrazide derivative, or a stereoisomer, or a pharmaceutically acceptable salt, or a solvate, or a prodrug molecule thereof, the isoxazoline hydrazide derivative prepared by the preparation method, or a stereoisomer, or a pharmaceutically acceptable salt, or a solvate, or a prodrug molecule thereof, and the application of the composition, or the preparation in controlling agricultural pests;

preferably, the agricultural pest includes, but is not limited to, lepidopteran and/or hemipteran pests; more preferably, the agricultural pest includes, but is not limited to, one or more of diamond back moth, spodoptera frugiperda, rice planthopper or aphid.

In a sixth aspect, the invention further provides a method for controlling agricultural pests, wherein the isoxazoline hydrazide derivative, or a stereoisomer, or a pharmaceutically acceptable salt, or a solvate, or a prodrug molecule thereof is taken, the isoxazoline hydrazide derivative, or a stereoisomer, or a pharmaceutically acceptable salt, or a solvate, or a prodrug molecule thereof prepared by the preparation method acts on pests or living environments thereof;

The invention provides a method for preparing hydrazide by reacting isoxazoline ester with hydrazine hydrate, and reacting with acyl chloride or aldehyde to prepare isoxazoline-containing hydrazide derivatives (structures shown in formulas (I) and (II)), which has good insecticidal activity on Spodoptera frugiperda. A pesticide or a salt thereof which is useful for controlling lepidopteran pests such as Spodoptera frugiperda which are harmful to crops such as corn and sorghum, and a pest control agent containing the same. The structure and the preparation process are simple, the bisazide insecticidal composition can be used as a good substitute for a bishydrazide insecticide, and the application prospect is wide.

Detailed Description

The invention discloses isoxazoline hydrazide derivatives, and a preparation method and application thereof, and a person skilled in the art can appropriately improve process parameters by referring to the content. It is expressly intended that all such similar substitutes and modifications which would be obvious to one skilled in the art are deemed to be included in the invention. While the methods and applications of this invention have been described in terms of preferred embodiments, it will be apparent to those of ordinary skill in the art that variations and modifications in the methods and applications described herein, as well as other suitable variations and combinations, may be made to implement and use the techniques of this invention without departing from the spirit and scope of the invention.

The invention aims to provide an isoxazoline derivative containing a hydrazide unit and a preparation method thereof.

It is still another object of the present invention to provide a composition comprising the above compound or a stereoisomer thereof, or a salt or solvate thereof.

It is a further object of the present invention to provide the above compounds or stereoisomers thereof, or salts or solvates thereof, or the use of said compositions.

Another object of the present invention is to provide a method for controlling agricultural pests using the above compound or a stereoisomer thereof, or a salt or solvate thereof, or the composition.

The isoxazoline derivative containing the hydrazide derivative has the structural general formula (I), (II) as follows:

in order to realize the purpose, the invention adopts the following technical scheme:

wherein:

Z is selected from O or S.

The substitution refers to the optional substitution of one or more of halogen, nitryl, hydroxyl, amino, sulfydryl, C1-C6 alkyl;

the preparation method of the derivative comprises the following steps:

preferably, further comprising:

preferably, further comprising:

further comprising:

preferably, further comprising:

preferably, further comprising:

the invention also provides a composition containing the compound or the stereoisomer or the salt or the solvate thereof, and an agriculturally acceptable auxiliary agent or bactericide, pesticide or herbicide; preferably, the formulation of the composition is selected from Emulsifiable Concentrates (EC), Dusts (DP), Wettable Powders (WP), Granules (GR), Aqueous Solutions (AS), Suspension Concentrates (SC), ultra low volume sprays (ULV), Soluble Powders (SP), Microcapsules (MC), smoking agents (FU), aqueous Emulsions (EW), water dispersible granules (WG).

The compound or the stereoisomer thereof, or the salt or the solvate thereof, or the composition can be used for controlling agricultural pests, wherein the agricultural pests are lepidoptera pests and hemiptera pests; more preferably, the agricultural pest is plutella xylostella, spodoptera frugiperda, and plant hopper.

The invention provides a method for preventing and controlling agricultural pests, which enables the compound or the stereoisomer thereof, the salt thereof or the solvate thereof, or the composition to act on the pests or the living environment thereof; preferably, the agricultural pest is a lepidopteran pest and a hemipteran pest; more preferably, the agricultural pest is plutella xylostella, spodoptera frugiperda, and plant hopper.

The term "alkyl" as used herein is intended to include both branched and straight chain saturated hydrocarbon radicals having the specified number of carbon atoms. For example, "C1-10 alkyl" (or alkylene) is intended to be C1, C2, C3, C4, C5, C6, C7, C8, C9 and C10 alkyl. Further, for example, "C1-6 alkyl" denotes an alkyl group having 1 to 6 carbon atoms. Alkyl groups may be unsubstituted or substituted such that one or more of its hydrogen atoms are replaced with another chemical group. Examples of alkyl groups include, but are not limited to, methyl (Me), ethyl (Et), propyl (e.g., n-propyl and isopropyl), butyl (e.g., n-butyl, isobutyl, t-butyl), pentyl (e.g., n-pentyl, isopentyl, neopentyl), and the like.

"alkenyl" is a hydrocarbon group that includes both straight and branched chain structures and has one or more carbon-carbon double bonds that occur at any stable point in the chain. For example, "C2-6 alkenyl" (or alkenylene) is intended to include C2, C3, C4, C5, and C6 alkenyl. Examples of alkenyl groups include, but are not limited to, ethenyl, 1-propenyl, 2-butenyl, 3-butenyl, 2-pentenyl, 3-pentenyl, 4-pentenyl, 2-hexenyl, 3-hexenyl, 4-hexenyl, 5-hexenyl, 2-methyl-2-propenyl, 4-methyl-3-pentenyl, and the like.

The term "cycloalkyl" refers to cycloalkyl groups, including mono-, bi-or polycyclic ring systems. C3-7 cycloalkyl is intended to include C3, C4, C5, C6 and C7 cycloalkyl. Examples of cycloalkyl groups include, but are not limited to, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, norbornyl, and the like. As used herein, "carbocycle" or "carbocycle residue" refers to any stable 3,4, 5, 6 or 7-membered monocyclic or bicyclic or 7, 8, 9, 10, 11, 12 or 13-membered bi-or tricyclic ring which may be saturated, partially unsaturated, unsaturated or aromatic. Examples of such carbocycles include, but are not limited to, cyclopropyl, cyclobutyl, cyclobutenyl, cyclopentyl, pentenyl, cyclohexyl, cyclohexenyl, cycloheptyl, cycloheptenyl, adamantyl, cyclooctyl, cyclooctenyl, cyclooctadiene, [3.3.0] bicyclooctane, [4.3.0] bicyclononane, [4.4.0] bicyclodecane, [2.2.2] bicyclooctane, fluorenyl, phenyl, naphthyl, indanyl, adamantyl, anthracenyl, and tetrahydronaphthyl (tetralin). As mentioned above, bridged rings are also included in the definition of carbocyclic rings (e.g., [2.2.2] bicyclooctane). Preferred carbocycles, if not otherwise stated, are cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl and phenyl. When the term "carbocycle" is used, it is intended to include "aryl". A bridged ring occurs when one or more carbon atoms connects two non-adjacent carbon atoms. Preferred bridges are one or two carbon atoms. It is pointed out that the bridge always converts a single ring into a double ring. When the rings are bridged, substituents of the rings are also present on the bridge.

The term "aryl" refers to monocyclic or bicyclic aromatic hydrocarbon groups having 6 to 12 carbon atoms in the ring portion, such as phenyl and naphthyl.

The term "halogen" or "halogen atom" refers to fluorine, chlorine, bromine and iodine.

The term "heteroaryl" refers to substituted and unsubstituted aromatic 5 or 6 membered monocyclic groups, 9-or 10-membered bicyclic groups, and 11 to 14 membered tricyclic groups having at least one heteroatom (O, S or N) in at least one ring, said heteroatom containing ring preferably having 1, 2 or 3 heteroatoms selected from O, S and N. The heteroatom-containing heteroaryl groups can contain one or two oxygen or sulfur atoms per ring and/or from 1 to 4 nitrogen atoms, provided that the total number of heteroatoms in each ring is 4 or less and each ring has at least one carbon atom. The fused rings completing the bicyclic and tricyclic groups may contain only carbon atoms and may be saturated, partially saturated, or unsaturated. The nitrogen and sulfur atoms may optionally be oxidized and the nitrogen atoms may optionally be quaternized. Bicyclic or tricyclic heteroaryl groups must include at least one fully aromatic ring, but other fused rings may be aromatic or non-aromatic. The heteroaryl group may be attached at any available nitrogen or carbon atom of any ring. If the other ring is cycloalkyl or heterocyclic, it is additionally optionally substituted with ═ O (oxygen), as valency permits.

The isoxazoline hydrazide derivative provided by the invention has good insecticidal activity on spodoptera frugiperda. A pesticide or a salt thereof which is useful for controlling lepidopteran pests such as Spodoptera frugiperda which are harmful to crops such as corn and sorghum, and a pest control agent containing the same. The structure and the preparation process are simple, the bisazide insecticidal composition can be used as a good substitute for a bishydrazide insecticide, and the application prospect is wide.

In the isoxazoline hydrazide derivative and the preparation method and the application thereof provided by the invention, the used raw materials and reagents can be purchased from the market.

The invention is further illustrated by the following examples:

example 1: 4- (5- (3, 5-dichlorophenyl) -5- (trifluoromethyl) -4, 5-dihydroisoxazol-3-yl) -N' - (4-fluorobenzoyl) -2-methylbenzoyl hydrazine

(1) Preparation of methyl (E) -4- ((hydroxyimino) methyl) -2-methylbenzoate

Adding potassium carbonate (13.8g, 100mmol) and hydroxylamine hydrochloride (6.9g, 100mmol) into 50ml of methanol solution, dropwise adding 4-formyl-2-methyl benzoate (17.8g, 100mmol), reacting at 35 ℃ for 2-4h, after the reaction is completed, washing with water, extracting with ethyl acetate for three times, desolventizing the reaction mixture under reduced pressure, stirring with silica gel, and separating by a chromatographic column to obtain 17.7g of white solid with the yield of 92%.

(2) Preparation of methyl 4- (5- (3, 5-dichlorophenyl) -5- (trifluoromethyl) -4, 5-dihydroisoxazol-3-yl) -2-methylbenzoate:

methyl (E) -4- ((hydroxyimino) methyl) -2-methylbenzoate (9.65g, 50mmol), NCS (9.97g, 75mmol) and DMF (75mL) were mixed in a 250mL three-necked flask and reacted at 40 ℃ for 2-4 h. After the reaction is finished, 1, 3-dichloro-5- (3,3, 3-trifluoroprop-1-en-2-yl) benzene (15.6g, 65mmol) and triethylamine (10.1 g.100mol) are added for reaction at room temperature for 18h, the reaction mixture is decompressed and desolventized, silica gel is stirred, a chromatographic column is used for separating to obtain 19.4g of white solid, and the yield is 90%.

(3) Preparation of 4- (5- (3, 5-dichlorophenyl) -5- (trifluoromethyl) -4, 5-dihydroisoxazol-3-yl) -2-methylbenzoyl hydrazine:

methyl 4- (5- (3, 5-dichlorophenyl) -5- (trifluoromethyl) -4, 5-dihydroisoxazol-3-yl) -2-methylbenzoate (4.31g, 10mmol), 80% hydrazine hydrate (12.5g, 20mmol) and methanol (100mL) were added to a 500mL three-necked round-bottomed flask, and after the reaction was heated to reflux for 8-12 h, the reaction was cooled to room temperature, 50mL of a saturated aqueous sodium chloride solution was added, ethyl acetate was extracted (3X 100mL), the organic phases were combined, dried over anhydrous sodium sulfate, and the solvent was rotary-dried to give a pale yellow solid (3.92 g, yield 91%).

(4) Preparation of 4- (5- (3, 5-dichlorophenyl) -5- (trifluoromethyl) -4, 5-dihydroisoxazol-3-yl) -N' - (4-fluorobenzoyl) -2-methylbenzoyl hydrazine:

4- (5- (3, 5-dichlorophenyl) -5- (trifluoromethyl) -4, 5-dihydroisoxazol-3-yl) -2-methylbenzoyl hydrazine (0.431g, 1mmol) and triethylamine (0.131g, 1.3mmol) were charged into a 100mL three-necked round-bottomed flask, 10mL of dichloromethane was added, and a solution of 4-fluorobenzoyl chloride (0.204g, 1.3mmol) in dichloromethane was added dropwise, followed by reaction at room temperature for 8 to 12 hours. After the reaction, the reaction mixture was desolventized under reduced pressure, stirred with silica gel, and separated by column chromatography to obtain 0.304g of a yellow solid with a yield of 55%.

Example 2: 4- (5- (3, 5-dichlorophenyl) -5- (trifluoromethyl) -4, 5-dihydroisoxazol-3-yl) -2-methyl-N' - (4- (trifluoromethyl) benzoyl) benzoylhydrazine

(1) Preparation of methyl 4- (5- (3, 5-dichlorophenyl) -5- (trifluoromethyl) -4, 5-dihydroisoxazol-3-yl) -2-methylbenzoate: the same as in (2) of example 1;

(2) preparation of 4- (5- (3, 5-dichlorophenyl) -5- (trifluoromethyl) -4, 5-dihydroisoxazol-3-yl) -2-methylbenzoyl hydrazine: the same as in (3) in example 1;

(3) preparation of 4- (5- (3, 5-dichlorophenyl) -5- (trifluoromethyl) -4, 5-dihydroisoxazol-3-yl) -N' - (4-trifluoromethylbenzoyl) -2-methylbenzoyl hydrazine:

4- (5- (3, 5-dichlorophenyl) -5- (trifluoromethyl) -4, 5-dihydroisoxazol-3-yl) -2-methylbenzoyl hydrazine (0.431g, 1mmol) and triethylamine (0.131g, 1.3mmol) were charged into a 100mL three-necked round-bottomed flask, 10mL of dichloromethane was added, and a solution of 4-trifluoromethylbenzoyl chloride (0.270g, 1.3mmol) in dichloromethane was added dropwise and reacted at room temperature for 8 to 12 hours. After the reaction, the reaction mixture was desolventized under reduced pressure, stirred with silica gel, and separated by a column chromatography to obtain 0.313g of a yellow solid with a yield of 52%.

Example 3: n' - (cyclopropanecarbonyl) -4- (5- (3, 5-dichlorophenyl) -5- (trifluoromethyl) -4, 5-dihydroisoxazol-3-yl) benzoylhydrazine

(3) preparation of N' - (cyclopropanecarbonyl) -4- (5- (3, 5-dichlorophenyl) -5- (trifluoromethyl) -4, 5-dihydroisoxazol-3-yl) -2-methylbenzoyl hydrazine:

4- (5- (3, 5-dichlorophenyl) -5- (trifluoromethyl) -4, 5-dihydroisoxazol-3-yl) -2-methylbenzoyl hydrazine (0.431g, 1mmol) and triethylamine (0.131g, 1.3mmol) were charged into a 100mL three-necked round-bottomed flask, 10mL of dichloromethane was added, and a solution of cyclopropylacyl chloride (0.135g, 1.3mmol) in dichloromethane was added dropwise, followed by reaction at room temperature for 8 to 12 hours. After the reaction, the reaction mixture was desolventized under reduced pressure, stirred with silica gel, and separated by a column chromatography to obtain 0.364g of a yellow solid with a yield of 73%.

Example 4: 4- (5- (3, 5-dichlorophenyl) -5- (trifluoromethyl) -4, 5-dihydroisoxazol-3-yl) -N' - (2-fluoro-4-methylbenzoyl) -2-methylbenzoyl hydrazine

(3) preparation of 4- (5- (3, 5-dichlorophenyl) -5- (trifluoromethyl) -4, 5-dihydroisoxazol-3-yl) -N' - (2-fluoro-4-methylbenzoyl) -2-methylbenzoyl hydrazine:

4- (5- (3, 5-dichlorophenyl) -5- (trifluoromethyl) -4, 5-dihydroisoxazol-3-yl) -2-methylbenzoyl hydrazine (0.431g, 1mmol) and triethylamine (0.224g, 1.3mmol) were charged into a 100mL three-necked round-bottomed flask, 10mL of dichloromethane was added, a solution of 2-fluoro-4-methylbenzoyl chloride (0.200g, 1.3mmol) in dichloromethane was added dropwise, and the mixture was reacted at room temperature for 8 to 12 hours. After the reaction, the reaction mixture was desolventized under reduced pressure, stirred with silica gel, and separated by column chromatography to obtain 0.210g of a yellow solid with a yield of 37%.

Example 5: 4- (5- (3, 5-dichlorophenyl) -5- (trifluoromethyl) -4, 5-dihydroisoxazol-3-yl) -N' - (2-fluoro-5-methylbenzoyl) -2-methylbenzoyl hydrazine

(3) preparation of 4- (5- (3, 5-dichlorophenyl) -5- (trifluoromethyl) -4, 5-dihydroisoxazol-3-yl) -N' - (2-fluoro-5-methylbenzoyl) -2-methylbenzoyl hydrazine:

4- (5- (3, 5-dichlorophenyl) -5- (trifluoromethyl) -4, 5-dihydroisoxazol-3-yl) -2-methylbenzoyl hydrazine (0.431g, 1mmol) and triethylamine (0.224g, 1.3mmol) were charged into a 100mL three-necked round-bottomed flask, 10mL of dichloromethane was added, a solution of 2-fluoro-5-methylbenzoyl chloride (0.200g, 1.3mmol) in dichloromethane was added dropwise, and the mixture was reacted at room temperature for 8 to 12 hours. After the reaction, the reaction mixture was desolventized under reduced pressure, stirred with silica gel, and separated by column chromatography to obtain 0.244g of yellow solid with a yield of 43%.

Example 6: 4- (5- (3, 5-dichlorophenyl) -5- (trifluoromethyl) -4, 5-dihydroisoxazol-3-yl) -N' - (2-fluoro-4- (trifluoromethyl) benzoyl) -2-methylbenzoyl hydrazine

(3) preparation of 4- (5- (3, 5-dichlorophenyl) -5- (trifluoromethyl) -4, 5-dihydroisoxazol-3-yl) -N' - (2-fluoro-4- (trifluoromethyl) benzoyl) -2-methylbenzoyl hydrazine:

4- (5- (3, 5-dichlorophenyl) -5- (trifluoromethyl) -4, 5-dihydroisoxazol-3-yl) -2-methylbenzoyl hydrazine (0.431g, 1mmol) and triethylamine (0.224g, 1.3mmol) were charged into a 100mL three-necked round-bottomed flask, 10mL of dichloromethane was added, and a solution of 2-fluoro-4-trifluoromethylbenzoyl chloride (0.294g, 1.3mmol) in dichloromethane was added dropwise and reacted at room temperature for 8 to 12 hours. After the reaction is finished, the reaction mixture is decompressed and desolventized, the silica gel is stirred, and a chromatographic column is used for separating to obtain 0.373g of yellow solid, wherein the yield is 60%.

Example 7: 4- (5- (3, 5-dichlorophenyl) -5- (trifluoromethyl) -4, 5-dihydroisoxazol-3-yl) -2-methyl-N' - (4- (trifluoromethoxy) benzoyl) benzoylhydrazine

(3) preparation of 4- (5- (3, 5-dichlorophenyl) -5- (trifluoromethyl) -4, 5-dihydroisoxazol-3-yl) -2-methyl-N' - (4- (trifluoromethoxy) benzoyl hydrazine:

4- (5- (3, 5-dichlorophenyl) -5- (trifluoromethyl) -4, 5-dihydroisoxazol-3-yl) -2-methylbenzoyl hydrazine (0.431g, 1mmol) and triethylamine (0.224g, 1.3mmol) were charged into a 100mL three-necked round-bottomed flask, 10mL of dichloromethane was added, and a solution of 2-fluoro-4-trifluoromethylbenzoyl chloride (0.294g, 1.3mmol) in dichloromethane was added dropwise and reacted at room temperature for 8 to 12 hours. After the reaction, the reaction mixture was desolventized under reduced pressure, stirred with silica gel, and separated by a column chromatography to obtain 0.341g of a yellow solid with a yield of 55%.

Example 8: 4- (5- (3, 5-dichlorophenyl) -5- (trifluoromethyl) -4, 5-dihydroisoxazol-3-yl) -N' - (3-fluoro-5- (trifluoromethyl) benzoyl) -2-methylbenzoyl hydrazine

(3) preparation of 4- (5- (3, 5-dichlorophenyl) -5- (trifluoromethyl) -4, 5-dihydroisoxazol-3-yl) -N' - (3-fluoro-5- (trifluoromethyl) benzoyl) -2-methylbenzoyl hydrazine:

4- (5- (3, 5-dichlorophenyl) -5- (trifluoromethyl) -4, 5-dihydroisoxazol-3-yl) -2-methylbenzoyl hydrazine (0.431g, 1mmol) and triethylamine (0.224g, 1.3mmol) were charged into a 100mL three-necked round-bottomed flask, 10mL of dichloromethane was added, a solution of 3-fluoro-5-trifluoromethylbenzoyl chloride (0.294g, 1.3mmol) in dichloromethane was added dropwise, and the mixture was reacted at room temperature for 8 to 12 hours. After the reaction, the reaction mixture was desolventized under reduced pressure, stirred with silica gel, and separated by a column chromatography to obtain 0.255g of a yellow solid with a yield of 41%.

Example 9: n' - (4-bromo-3-chlorobenzoyl) -4- (5- (3, 5-dichlorophenyl) -5- (trifluoromethyl) -4, 5-dihydroisoxazol-3-yl) -2-methylbenzoyl hydrazine

(3) preparation of N' - (4-bromo-3-chlorobenzoyl) -4- (5- (3, 5-dichlorophenyl) -5- (trifluoromethyl) -4, 5-dihydroisoxazol-3-yl) -2-methylbenzoyl hydrazine:

4- (5- (3, 5-dichlorophenyl) -5- (trifluoromethyl) -4, 5-dihydroisoxazol-3-yl) -2-methylbenzoyl hydrazine (0.431g, 1mmol) and triethylamine (0.224g, 1.3mmol) were charged into a 100mL three-necked round-bottomed flask, 10mL of dichloromethane was added, a solution of 3-chloro-4-bromobenzoyl chloride (0.294g, 1.3mmol) in dichloromethane was added dropwise, and the mixture was reacted at room temperature for 8 to 12 hours. After the reaction, the reaction mixture was desolventized under reduced pressure, stirred with silica gel, and separated by a column chromatography to obtain 0.265g of a yellow solid with a yield of 41%.

Example 10: 2-bromo-N' - (4- (5- (3, 5-dichlorophenyl) -5- (trifluoromethyl) -4, 5-dihydroisoxazol-3-yl) -2-methylbenzoyl) -4-fluorobenzoyl hydrazine

(3) 2-bromo-N' - (4- (5- (3, 5-dichlorophenyl) -5- (trifluoromethyl) -4, 5-dihydroisoxazol-3-yl) -2-methylbenzoyl) -4-fluorobenzoyl hydrazine:

4- (5- (3, 5-dichlorophenyl) -5- (trifluoromethyl) -4, 5-dihydroisoxazol-3-yl) -2-methylbenzoyl hydrazine (0.431g, 1mmol) and triethylamine (0.224g, 1.3mmol) were charged into a 100mL three-necked round-bottomed flask, 10mL of dichloromethane was added, and a solution of 2-bromo-4-fluorobenzoyl chloride (0.305g, 1.3mmol) in dichloromethane was added dropwise, followed by reaction at room temperature for 8 to 12 hours. After the reaction, the reaction mixture was desolventized under reduced pressure, stirred with silica gel, and separated by column chromatography to obtain 0.266g of a yellow solid with a yield of 42%.

Example 11: n' - (2-chloro-6-fluorobenzoyl) -4- (5- (3, 5-dichlorophenyl) -5- (trifluoromethyl) -4, 5-dihydroisoxazol-3-yl) -2-methylbenzoyl hydrazine

4- (5- (3, 5-dichlorophenyl) -5- (trifluoromethyl) -4, 5-dihydroisoxazol-3-yl) -2-methylbenzoyl hydrazine (0.431g, 1mmol) and triethylamine (0.224g, 1.3mmol) were charged into a 100mL three-necked round-bottomed flask, 10mL of dichloromethane was added, a dichloromethane solution of 2-fluoro-6-chlorobenzoyl chloride (0.250g, 1.3mmol) was added dropwise, and the reaction was carried out at room temperature for 8 to 12 hours. After the reaction, the reaction mixture was desolventized under reduced pressure, stirred with silica gel, and separated by column chromatography to obtain 0.247g of yellow solid with a yield of 42%.

Example 12: n' - (4- (5- (3, 5-dichlorophenyl) -5- (trifluoromethyl) -4, 5-dihydroisoxazol-3-yl) -2-methylbenzoyl) -2,4, 5-trifluorobenzoylhydrazine

(3) n' - (4- (5- (3, 5-dichlorophenyl) -5- (trifluoromethyl) -4, 5-dihydroisoxazol-3-yl) -2-methylbenzoyl) -2,4, 5-trifluorobenzoyl hydrazine:

4- (5- (3, 5-dichlorophenyl) -5- (trifluoromethyl) -4, 5-dihydroisoxazol-3-yl) -2-methylbenzoyl hydrazine (0.431g, 1mmol) and triethylamine (0.224g, 1.3mmol) were charged into a 100mL three-necked round-bottomed flask, 10mL of dichloromethane was added, a solution of 2,4, 5-trifluorobenzoyl chloride (0.252g, 1.3mmol) in dichloromethane was added dropwise, and the mixture was reacted at room temperature for 8 to 12 hours. After the reaction is finished, the reaction mixture is decompressed and desolventized, the silica gel is stirred, and a chromatographic column is used for separating to obtain 0.295g of yellow solid, wherein the yield is 50%.

Example 13: 4- (5- (3, 5-dichlorophenyl) -5- (trifluoromethyl) -4, 5-dihydroisoxazol-3-yl) -N' - (2-fluorobenzoyl) -2-methylbenzoyl hydrazine

(3)4- (5- (3, 5-dichlorophenyl) -5- (trifluoromethyl) -4, 5-dihydroisoxazol-3-yl) -N' - (2-fluorobenzoyl) -2-methylbenzoyl hydrazine:

4- (5- (3, 5-dichlorophenyl) -5- (trifluoromethyl) -4, 5-dihydroisoxazol-3-yl) -2-methylbenzoyl hydrazine (0.431g, 1mmol) and triethylamine (0.224g, 1.3mmol) were charged into a 100mL three-necked round-bottomed flask, 10mL of dichloromethane was added, and a solution of 2-fluorobenzoyl chloride (0.205g, 1.3mmol) in dichloromethane was added dropwise, followed by reaction at room temperature for 8 to 12 hours. After the reaction, the reaction mixture was desolventized under reduced pressure, stirred with silica gel, and separated by a column chromatography to obtain 0.265g of a yellow solid with a yield of 48%.

Example 14: 4- (5- (3, 5-dichlorophenyl) -5- (trifluoromethyl) -4, 5-dihydroisoxazol-3-yl) -N' - (5-fluoro-2-methylbenzoyl) -2-methylbenzoyl hydrazine

4- (5- (3, 5-dichlorophenyl) -5- (trifluoromethyl) -4, 5-dihydroisoxazol-3-yl) -2-methylbenzoyl hydrazine (0.431g, 1mmol) and triethylamine (0.224g, 1.3mmol) were charged into a 100mL three-necked round-bottomed flask, 10mL of dichloromethane was added, a solution of 2-methyl-4-fluorobenzoyl chloride (0.224g, 1.3mmol) in dichloromethane was added dropwise, and the mixture was reacted at room temperature for 8 to 12 hours. After the reaction, the reaction mixture was desolventized under reduced pressure, stirred with silica gel, and separated by a column chromatography to obtain 0.260g of a yellow solid with a yield of 45%.

Example 15: 4- (5- (3, 5-dichlorophenyl) -5- (trifluoromethyl) -4, 5-dihydroisoxazol-3-yl) -N' - (2-fluoro-6-iodobenzoyl) -2-methylbenzoyl hydrazine

(3)4- (5- (3, 5-dichlorophenyl) -5- (trifluoromethyl) -4, 5-dihydroisoxazol-3-yl) -N' - (2-fluoro-6-iodobenzoyl) -2-methylbenzoyl hydrazine:

4- (5- (3, 5-dichlorophenyl) -5- (trifluoromethyl) -4, 5-dihydroisoxazol-3-yl) -2-methylbenzoyl hydrazine (0.431g, 1mmol) and triethylamine (0.224g, 1.3mmol) were charged into a 100mL three-necked round-bottomed flask, 10mL of dichloromethane was added, and a solution of 2-fluoro-6-iodobenzoyl chloride (0.369g, 1.3mmol) in dichloromethane was added dropwise and reacted at room temperature for 8 to 12 hours. After the reaction is finished, the reaction mixture is decompressed and desolventized, the silica gel is stirred, and a chromatographic column is used for separating to obtain 0.272g of yellow solid, wherein the yield is 40%.

Example 16: n' - (3-chlorobenzoyl) -4- (5- (3, 5-dichlorophenyl) -5- (trifluoromethyl) -4, 5-dihydroisoxazol-3-yl) -2-methylbenzoyl hydrazine

(3) n' - (3-chlorobenzoyl) -4- (5- (3, 5-dichlorophenyl) -5- (trifluoromethyl) -4, 5-dihydroisoxazol-3-yl) -2-methylbenzoyl hydrazine:

4- (5- (3, 5-dichlorophenyl) -5- (trifluoromethyl) -4, 5-dihydroisoxazol-3-yl) -2-methylbenzoyl hydrazine (0.431g, 1mmol) and triethylamine (0.224g, 1.3mmol) were charged into a 100mL three-necked round-bottomed flask, 10mL of dichloromethane was added, and a solution of 3-chlorobenzoyl chloride (0.226g, 1.3mmol) in dichloromethane was added dropwise, followed by reaction at room temperature for 8 to 12 hours. After the reaction, the reaction mixture was desolventized under reduced pressure, stirred with silica gel, and separated by column chromatography to obtain 0.210g of a yellow solid with a yield of 37%.

Example 17: n' - (4-chlorobenzoyl) -4- (5- (3, 5-dichlorophenyl) -5- (trifluoromethyl) -4, 5-dihydroisoxazol-3-yl) -2-methylbenzoyl hydrazine

(3) n' - (4-chlorobenzoyl) -4- (5- (3, 5-dichlorophenyl) -5- (trifluoromethyl) -4, 5-dihydroisoxazol-3-yl) -2-methylbenzoyl hydrazine:

4- (5- (3, 5-dichlorophenyl) -5- (trifluoromethyl) -4, 5-dihydroisoxazol-3-yl) -2-methylbenzoyl hydrazine (0.431g, 1mmol) and triethylamine (0.224g, 1.3mmol) were charged into a 100mL three-necked round-bottomed flask, 10mL of dichloromethane was added, and a solution of 4-chlorobenzoyl chloride (0.226g, 1.3mmol) in dichloromethane was added dropwise, followed by reaction at room temperature for 8 to 12 hours. After the reaction is finished, the reaction mixture is decompressed and desolventized, the silica gel is mixed with a sample, and the yellow solid is separated by a chromatographic column and is 0.199g, and the yield is 35%.

Example 18: n' - (3, 5-bis (trifluoromethyl) benzoyl) -4- (5- (3, 5-dichlorophenyl) -5- (trifluoromethyl) -4, 5-dihydroisoxazol-3-yl) -2-methylbenzoyl hydrazine

(3) n' - (3, 5-bis (trifluoromethyl) benzoyl) -4- (5- (3, 5-dichlorophenyl) -5- (trifluoromethyl) -4, 5-dihydroisoxazol-3-yl) -2-methylbenzoyl hydrazine:

4- (5- (3, 5-dichlorophenyl) -5- (trifluoromethyl) -4, 5-dihydroisoxazol-3-yl) -2-methylbenzoyl hydrazine (0.431g, 1mmol) and triethylamine (0.224g, 1.3mmol) were charged into a 100mL three-necked round-bottomed flask, 10mL of dichloromethane was added, a solution of 3, 5-bis (trifluoromethyl) benzoyl chloride (0.226g, 1.3mmol) in dichloromethane was added dropwise, and the mixture was reacted at room temperature for 8 to 12 hours. After the reaction, the reaction mixture was desolventized under reduced pressure, stirred with silica gel, and separated by a column chromatography to obtain 0.221g of a yellow solid with a yield of 33%.

Example 19: 4- (5- (3, 5-dichlorophenyl) -5- (trifluoromethyl) -4, 5-dihydroisoxazol-3-yl) -N' - (3-fluorobenzoyl) -2-methylbenzoyl hydrazine

(3)4- (5- (3, 5-dichlorophenyl) -5- (trifluoromethyl) -4, 5-dihydroisoxazol-3-yl) -N' - (3-fluorobenzoyl) -2-methylbenzoyl hydrazine:

4- (5- (3, 5-dichlorophenyl) -5- (trifluoromethyl) -4, 5-dihydroisoxazol-3-yl) -2-methylbenzoyl hydrazine (0.431g, 1mmol) and triethylamine (0.224g, 1.3mmol) were charged into a 100mL three-necked round-bottomed flask, 10mL of dichloromethane was added, and a solution of 3-fluorobenzoyl chloride (0.205g, 1.3mmol) in dichloromethane was added dropwise and reacted at room temperature for 8 to 12 hours. After the reaction, the reaction mixture was desolventized under reduced pressure, stirred with silica gel, and separated by column chromatography to obtain 0.238g of a yellow solid with a yield of 43%.

Example 20: 4-bromo-N' - (4- (5- (3, 5-dichlorophenyl) -5- (trifluoromethyl) -4, 5-dihydroisoxazol-3-yl) -2-methylbenzoyl) -2, 6-difluorobenzoyl hydrazine

(3) 4-bromo-N' - (4- (5- (3, 5-dichlorophenyl) -5- (trifluoromethyl) -4, 5-dihydroisoxazol-3-yl) -2-methylbenzoyl) -2, 6-difluorobenzoyl hydrazine:

4- (5- (3, 5-dichlorophenyl) -5- (trifluoromethyl) -4, 5-dihydroisoxazol-3-yl) -2-methylbenzoyl hydrazine (0.431g, 1mmol) and triethylamine (0.224g, 1.3mmol) were charged into a 100mL three-necked round-bottomed flask, 10mL of dichloromethane was added, and a solution of 3, 5-difluoro-4-bromobenzoyl chloride (0.232g, 1.3mmol) in dichloromethane was added dropwise and reacted at room temperature for 8 to 12 hours. After the reaction, the reaction mixture was desolventized under reduced pressure, stirred with silica gel, and separated by a column chromatography to obtain 0.266g of a yellow solid with a yield of 41%.

Example 21: n' - (4- (5- (3, 5-dichlorophenyl) -5- (trifluoromethyl) -4, 5-dihydroisoxazol-3-yl) -2-methylbenzoyl) -2-fluoro-3-nitrobenzoyl hydrazide

(3) n' - (4- (5- (3, 5-dichlorophenyl) -5- (trifluoromethyl) -4, 5-dihydroisoxazol-3-yl) -2-methylbenzoyl) -2-fluoro-3-nitrobenzoyl hydrazide:

4- (5- (3, 5-dichlorophenyl) -5- (trifluoromethyl) -4, 5-dihydroisoxazol-3-yl) -2-methylbenzoyl hydrazine (0.431g, 1mmol) and triethylamine (0.224g, 1.3mmol) were charged into a 100mL three-necked round-bottomed flask, 10mL of dichloromethane was added, and a solution of 3, 5-difluoro-4-bromobenzoyl chloride (0.64g, 1.3mmol) in dichloromethane was added dropwise and reacted at room temperature for 8 to 12 hours. After the reaction is finished, the reaction mixture is decompressed and desolventized, the silica gel is stirred, and a chromatographic column is used for separating to obtain 0.215g of yellow solid, wherein the yield is 36%.

Example 22: 4- (5- (3, 5-dichlorophenyl) -5- (trifluoromethyl) -4, 5-dihydroisoxazol-3-yl) -N' - (2, 4-difluorobenzoyl) -2-methylbenzoyl hydrazine

(3)4- (5- (3, 5-dichlorophenyl) -5- (trifluoromethyl) -4, 5-dihydroisoxazol-3-yl) -N' - (2, 4-difluorobenzoyl) -2-methylbenzoyl hydrazine:

4- (5- (3, 5-dichlorophenyl) -5- (trifluoromethyl) -4, 5-dihydroisoxazol-3-yl) -2-methylbenzoyl hydrazine (0.431g, 1mmol) and triethylamine (0.224g, 1.3mmol) were charged into a 100mL three-necked round-bottomed flask, 10mL of dichloromethane was added, and a solution of 3, 4-difluorobenzoyl chloride (0.229g, 1.3mmol) in dichloromethane was added dropwise and reacted at room temperature for 8 to 12 hours. After the reaction is finished, the reaction mixture is decompressed and desolventized, the silica gel is stirred, and a chromatographic column is used for separating to obtain 0.408g of yellow solid, wherein the yield is 72%.

Example 23: 4-chloro-N' - (4- (5- (3, 5-dichlorophenyl) -5- (trifluoromethyl) -4, 5-dihydroisoxazol-3-yl) -2-methylbenzoyl) -3-ethyl-1-methyl-1H-pyrazole-5-carbohydrazide

4- (5- (3, 5-dichlorophenyl) -5- (trifluoromethyl) -4, 5-dihydroisoxazol-3-yl) -2-methylbenzoyl hydrazine (0.431g, 1mmol) and triethylamine (0.224g, 1.3mmol) were charged into a 100mL three-necked round-bottomed flask, 10mL of dichloromethane was added, and a solution of 4-chloro-3-ethyl-1-methyl-1H-pyrazole-5-carbonyl chloride (0.269g, 1.3mmol) in dichloromethane was added dropwise, followed by reaction at room temperature for 8 to 12 hours. After the reaction, the reaction mixture was desolventized under reduced pressure, stirred with silica gel, and separated by column chromatography to obtain 0.228g of a yellow solid with a yield of 37%.

Example 24: 4- (5- (3, 5-dichlorophenyl) -5- (trifluoromethyl) -4, 5-dihydroisoxazol-3-yl) -N' - (4-fluorobenzoyl) benzoyl hydrazine

(3)4- (5- (3, 5-dichlorophenyl) -5- (trifluoromethyl) -4, 5-dihydroisoxazol-3-yl) -N' - (4-fluorobenzoyl) benzoyl hydrazine:

4- (5- (3, 5-dichlorophenyl) -5- (trifluoromethyl) -4, 5-dihydroisoxazol-3-yl) -2-methylbenzoyl hydrazine (0.431g, 1mmol) and triethylamine (0.224g, 1.3mmol) were charged into a 100mL three-necked round-bottomed flask, 10mL of dichloromethane was added, and a solution of 4-fluorobenzoyl chloride (0.205g, 1.3mmol) in dichloromethane was added dropwise, followed by reaction at room temperature for 8 to 12 hours. After the reaction, the reaction mixture was desolventized under reduced pressure, stirred with silica gel, and separated by a column chromatography to obtain 0.335g of a yellow solid with a yield of 62%.

Example 25: n' - (4- (5- (3, 5-dichlorophenyl) -5- (trifluoromethyl) -4, 5-dihydroisoxazol-3-yl) benzoyl) -2, 4-difluorobenzoyl hydrazine

(3) n' - (4- (5- (3, 5-dichlorophenyl) -5- (trifluoromethyl) -4, 5-dihydroisoxazol-3-yl) benzoyl) -2, 4-difluorobenzoyl hydrazine:

4- (5- (3, 5-dichlorophenyl) -5- (trifluoromethyl) -4, 5-dihydroisoxazol-3-yl) -2-methylbenzoyl hydrazine (0.431g, 1mmol) and triethylamine (0.224g, 1.3mmol) were charged into a 100mL three-necked round-bottomed flask, 10mL of dichloromethane was added, and a solution of 2, 4-difluorobenzoyl chloride (0.229g, 1.3mmol) in dichloromethane was added dropwise and reacted at room temperature for 8 to 12 hours. After the reaction, the reaction mixture was desolventized under reduced pressure, stirred with silica gel, and separated by a column chromatography to obtain 0.226g of a white solid with a yield of 41%.

Example 26: 3- (5- (3, 5-dichlorophenyl) -5- (trifluoromethyl) -4, 5-dihydroisoxazol-3-yl) -N' - (4-fluorobenzoyl) benzoyl hydrazine

(1) Preparation of methyl 4- (5- (3, 5-dichlorophenyl) -5- (trifluoromethyl) -4, 5-dihydroisoxazol-3-yl) -2-methylbenzoate:

methyl (E) -3- ((hydroxyimino) methyl) benzoate (8.95g, 50mmol), NCS (9.97g, 75mmol) and DMF (75mL) were mixed in a 250mL three-necked flask and reacted at 40 ℃ for 2-4 h. After the reaction is finished, 1, 3-dichloro-5- (3,3, 3-trifluoroprop-1-en-2-yl) benzene (15.6g, 65mmol) and triethylamine (10.1 g.100mol) are added for reaction at room temperature for 18h, the reaction mixture is decompressed and desolventized, silica gel is stirred, a chromatographic column is used for separating to obtain 19.2g of white solid, and the yield is 92%.

(2) Preparation of 4- (5- (3, 5-dichlorophenyl) -5- (trifluoromethyl) -4, 5-dihydroisoxazol-3-yl) -2-methylbenzoyl hydrazine:

methyl 4- (5- (3, 5-dichlorophenyl) -5- (trifluoromethyl) -4, 5-dihydroisoxazol-3-yl) -2-methylbenzoate (0.431g, 1mmol), 80% hydrazine hydrate (1.25g, 20mmol) and methanol (10mL) were added to a 500mL three-necked round-bottomed flask, and after the reaction was heated to reflux for 8-12 h, the reaction was cooled to room temperature, 50mL of a saturated aqueous sodium chloride solution was added, ethyl acetate was extracted (3X 10mL), the organic phases were combined, dried over anhydrous sodium sulfate, and the solvent was spin-dried to give 0.313g of a pale yellow solid.

4- (5- (3, 5-dichlorophenyl) -5- (trifluoromethyl) -4, 5-dihydroisoxazol-3-yl) -2-methylbenzoyl hydrazine (0.209g, 0.5mmol) and triethylamine (0.066g, 0.65mmol) were charged into a 100mL three-necked round-bottomed flask, 10mL of dichloromethane was added, and a solution of 4-fluorobenzoyl chloride (0.102g, 0.65mmol) in dichloromethane was added dropwise, followed by reaction at room temperature for 8 to 12 hours. After the reaction, the reaction mixture was desolventized under reduced pressure, stirred with silica gel and separated by a column chromatography to obtain 0.167g of a white solid.

Example 27: 4- (5- (3, 5-dichlorophenyl) -5- (trifluoromethyl) -4, 5-dihydroisoxazol-3-yl) -N' - (2, 6-dimethylbenzoyl) -2-methylbenzoyl hydrazine

(1) Preparation of methyl 4- (5- (3, 5-dichlorophenyl) -5- (trifluoromethyl) -4, 5-dihydroisoxazol-3-yl) -2-methylbenzoate: the same as in example 26 (1);

(2) preparation of 4- (5- (3, 5-dichlorophenyl) -5- (trifluoromethyl) -4, 5-dihydroisoxazol-3-yl) -2-methylbenzoyl hydrazine: the same as in example 26 (2);

(3)4- (5- (3, 5-dichlorophenyl) -5- (trifluoromethyl) -4, 5-dihydroisoxazol-3-yl) -N' - (2, 6-dimethylbenzoyl) -2-methylbenzoyl hydrazine:

4- (5- (3, 5-dichlorophenyl) -5- (trifluoromethyl) -4, 5-dihydroisoxazol-3-yl) -2-methylbenzoyl hydrazine (0.209g, 0.5mmol) and triethylamine (0.066g, 0.65mmol) were charged into a 100mL three-necked round-bottomed flask, 10mL of dichloromethane was added, a solution of 2, 6-dimethylbenzoyl chloride (0.109g, 0.65mmol) in dichloromethane was added dropwise, and the mixture was reacted at room temperature for 8 to 12 hours. After the reaction is finished, the reaction mixture is decompressed and desolventized, the silica gel is stirred, and the white solid of 0.90g is obtained by chromatographic column separation.

Example 28: 4- (5- (3, 5-dichlorophenyl) -5- (trifluoromethyl) -4, 5-dihydroisoxazol-3-yl) -N' - (3, 5-dimethylbenzoyl) -2-methylbenzoyl hydrazine

(3)4- (5- (3, 5-dichlorophenyl) -5- (trifluoromethyl) -4, 5-dihydroisoxazol-3-yl) -N' - (3, 5-dimethylbenzoyl) -2-methylbenzoyl hydrazine:

4- (5- (3, 5-dichlorophenyl) -5- (trifluoromethyl) -4, 5-dihydroisoxazol-3-yl) -2-methylbenzoyl hydrazine (0.209g, 0.5mmol) and triethylamine (0.066g, 0.65mmol) were charged into a 100mL three-necked round-bottomed flask, 10mL of dichloromethane was added, a solution of 3, 5-dimethylbenzoyl chloride (0.109g, 0.65mmol) in dichloromethane was added dropwise, and the mixture was reacted at room temperature for 8 to 12 hours. After the reaction, the reaction mixture was desolventized under reduced pressure, stirred with silica gel and separated by a column chromatography to obtain 0.147g of a white solid.

Example 29: 4- (5- (3, 5-dichlorophenyl) -5- (trifluoromethyl) -4, 5-dihydroisoxazol-3-yl) -N' - (4-methoxybenzoyl) -2-methylbenzoyl hydrazine

(1)4- (5- (3, 5-dichlorophenyl) -5- (trifluoromethyl) -4, 5-dihydroisoxazol-3-yl) -N' - (4-methoxybenzoyl) -2-methylbenzoyl hydrazine:

4- (5- (3, 5-dichlorophenyl) -5- (trifluoromethyl) -4, 5-dihydroisoxazol-3-yl) -2-methylbenzoyl hydrazine (0.209g, 0.5mmol) and triethylamine (0.066g, 0.65mmol) were charged into a 100mL three-necked round-bottomed flask, 10mL of dichloromethane was added, and a solution of 4-methoxybenzoyl chloride (0.110g, 0.65mmol) in dichloromethane was added dropwise, followed by reaction at room temperature for 8 to 12 hours. After the reaction, the reaction mixture was desolventized under reduced pressure, stirred with silica gel and separated by a column chromatography to obtain 0.169.5g of a white solid.

Example 30: 4- (5- (3, 5-dichlorophenyl) -5- (trifluoromethyl) -4, 5-dihydroisoxazol-3-yl) -2-methyl-N' - (2-methylbenzoyl) benzoyl hydrazine

(3)4- (5- (3, 5-dichlorophenyl) -5- (trifluoromethyl) -4, 5-dihydroisoxazol-3-yl) -N' - (2-methylbenzoyl) -2-methylbenzoyl hydrazine:

4- (5- (3, 5-dichlorophenyl) -5- (trifluoromethyl) -4, 5-dihydroisoxazol-3-yl) -2-methylbenzoyl hydrazine (0.209g, 0.5mmol) and triethylamine (0.066g, 0.65mmol) were charged into a 100mL three-necked round-bottomed flask, 10mL of dichloromethane was added, and a solution of 2-methylbenzoyl chloride (0.100g, 0.65mmol) in dichloromethane was added dropwise, followed by reaction at room temperature for 8 to 12 hours. After the reaction, the reaction mixture was desolventized under reduced pressure, stirred with silica gel and separated by a column chromatography to obtain 0.178.5g of a white solid.

Example 31: 4- (5- (3, 5-dichlorophenyl) -5- (trifluoromethyl) -4, 5-dihydroisoxazol-3-yl) -N' - (3-methoxybenzoyl) -2-methylbenzoyl hydrazine

(3)4- (5- (3, 5-dichlorophenyl) -5- (trifluoromethyl) -4, 5-dihydroisoxazol-3-yl) -N' - (3-methoxybenzoyl) -2-methylbenzoyl hydrazine:

4- (5- (3, 5-dichlorophenyl) -5- (trifluoromethyl) -4, 5-dihydroisoxazol-3-yl) -2-methylbenzoyl hydrazine (0.209g, 0.5mmol) and triethylamine (0.066g, 0.65mmol) were charged into a 100mL three-necked round-bottomed flask, 10mL of dichloromethane was added, and a solution of 3-methoxybenzoyl chloride (0.111g, 0.65mmol) in dichloromethane was added dropwise and reacted at room temperature for 8 to 12 hours. After the reaction, the reaction mixture was desolventized under reduced pressure, stirred with silica gel and separated by a column chromatography to obtain 0.147g of a white solid.

Example 32: 4- (5- (3, 5-dichlorophenyl) -5- (trifluoromethyl) -4, 5-dihydroisoxazol-3-yl) -2-methyl-N' - (2-methyl-4- (methylsulfonyl) benzoyl) hydrazide

(3)4- (5- (3, 5-dichlorophenyl) -5- (trifluoromethyl) -4, 5-dihydroisoxazol-3-yl) -2-methyl-N' - (2-methyl-4- (methylsulfonyl) benzoyl) hydrazide:

4- (5- (3, 5-dichlorophenyl) -5- (trifluoromethyl) -4, 5-dihydroisoxazol-3-yl) -2-methylbenzoyl hydrazine (0.209g, 0.5mmol) and triethylamine (0.066g, 0.65mmol) were charged into a 100mL three-necked round-bottomed flask, 10mL of dichloromethane was added, a solution of 2-methyl-4- (methylsulfonyl) benzoyl chloride (0.150g, 0.65mmol) in dichloromethane was added dropwise, and the mixture was reacted at room temperature for 8 to 12 hours. After the reaction is finished, the reaction mixture is decompressed and desolventized, the silica gel is stirred, and the white solid of 0.125g is obtained by chromatographic column separation.

Example 33: n' - (4- (5- (3, 5-dichlorophenyl) -5- (trifluoromethyl) -4, 5-dihydroisoxazol-3-yl) -2-methylbenzoyl) -2-fluoro-3-nitrobenzoyl hydrazide

4- (5- (3, 5-dichlorophenyl) -5- (trifluoromethyl) -4, 5-dihydroisoxazol-3-yl) -2-methylbenzoyl hydrazine (0.209g, 0.5mmol) and triethylamine (0.066g, 0.65mmol) were charged into a 100mL three-necked round-bottomed flask, 10mL of dichloromethane was added, a dichloromethane solution of 2-fluoro-3-nitrobenzoyl chloride (0.132g, 0.65mmol) was added dropwise, and the reaction was carried out at room temperature for 8 to 12 hours. After the reaction, the reaction mixture was desolventized under reduced pressure, stirred with silica gel and separated by a column chromatography to obtain 0.107g of a white solid.

Example 34: n' - (3-chloro-2, 2-dimethylpropionyl) -4- (5- (3, 5-dichlorophenyl) -5- (trifluoromethyl) -4, 5-dihydroisoxazol-3-yl) -2-methylbenzoyl hydrazine

(3) n' - (3-chloro-2, 2-dimethylpropionyl) -4- (5- (3, 5-dichlorophenyl) -5- (trifluoromethyl) -4, 5-dihydroisoxazol-3-yl) -2-methylbenzoyl hydrazine:

4- (5- (3, 5-dichlorophenyl) -5- (trifluoromethyl) -4, 5-dihydroisoxazol-3-yl) -2-methylbenzoyl hydrazine (0.209g, 0.5mmol) and triethylamine (0.066g, 0.65mmol) were charged into a 100mL three-necked round-bottomed flask, 10mL of dichloromethane was added, a solution of 3-chloro-2, 2-dimethylpropionyl chloride (0.101g, 0.65mmol) in dichloromethane was added dropwise, and the reaction was carried out at room temperature for 8 to 12 hours. After the reaction is finished, the reaction mixture is decompressed and desolventized, the silica gel is stirred, and the white solid of 0.85g is obtained by chromatographic column separation.

Example 35: 4- (5- (3, 5-dichlorophenyl) -5- (trifluoromethyl) -4, 5-dihydroisoxazol-3-yl) -N' - (2, 4-difluorobenzoyl) -2-methylbenzoyl hydrazine

4- (5- (3, 5-dichlorophenyl) -5- (trifluoromethyl) -4, 5-dihydroisoxazol-3-yl) -2-methylbenzoyl hydrazine (0.209g, 0.5mmol) and triethylamine (0.066g, 0.65mmol) were charged into a 100mL three-necked round-bottomed flask, 10mL of dichloromethane was added, a solution of 2, 2-difluorobenzoyl chloride (0.114g, 0,65mmol) in dichloromethane was added dropwise, and the mixture was reacted at room temperature for 8 to 12 hours. After the reaction, the reaction mixture was desolventized under reduced pressure, stirred with silica gel and separated by a column chromatography to obtain 0.206g of a white solid.

Example 36: 4-chloro-N' - (4- (5- (3, 5-dichlorophenyl) -5- (trifluoromethyl) -4, 5-dihydroisoxazol-3-yl) -2-methylbenzoyl) -3-ethyl-1-methyl-1H-pyrazole-5-carbohydrazide

(3) 4-chloro-N' - (4- (5- (3, 5-dichlorophenyl) -5- (trifluoromethyl) -4, 5-dihydroisoxazol-3-yl) -2-methylbenzoyl) -3-ethyl-1-methyl-1H-pyrazole-5-carbohydrazide:

4- (5- (3, 5-dichlorophenyl) -5- (trifluoromethyl) -4, 5-dihydroisoxazol-3-yl) -2-methylbenzoyl hydrazine (0.209g, 0.5mmol) and triethylamine (0.066g, 0.65mmol) were charged into a 100mL three-necked round-bottomed flask, 10mL of dichloromethane was added, a solution of 4-chloro-3-ethyl-1-methyl-1H-pyrazole-5-carbonyl chloride (0.134g, 0,65mmol) in dichloromethane was added dropwise, and the mixture was reacted at room temperature for 8 to 12 hours. After the reaction, the reaction mixture was desolventized under reduced pressure, stirred with silica gel and separated by a column chromatography to obtain 0.111g of a white solid.

Example 37: 4- (5- (3, 5-dichlorophenyl) -5- (trifluoromethyl) -4, 5-dihydroisoxazol-3-yl) -N' - (2-methoxyacetyl) -2-methylbenzoyl hydrazine

(3)4- (5- (3, 5-dichlorophenyl) -5- (trifluoromethyl) -4, 5-dihydroisoxazol-3-yl) -N' - (2-methoxyacetyl) -2-methylbenzoyl hydrazine:

4- (5- (3, 5-dichlorophenyl) -5- (trifluoromethyl) -4, 5-dihydroisoxazol-3-yl) -2-methylbenzoyl hydrazine (0.209g, 0.5mmol) and triethylamine (0.066g, 0.65mmol) were charged into a 100mL three-necked round-bottomed flask, 10mL of dichloromethane was added, and a solution of 2-methoxyacetyl chloride (0.70g, 0,65mmol) in dichloromethane was added dropwise, followed by reaction at room temperature for 8 to 12 hours. After the reaction, the reaction mixture was desolventized under reduced pressure, stirred with silica gel and separated by a column chromatography to obtain 0.106g of a white solid.

Example 38: n' - (4-Chlorobenzylidene) -4- (5- (3, 5-dichlorophenyl) -5- (trifluoromethyl) -4, 5-dihydroisoxazol-3-yl) -2-methylbenzoyl hydrazine

(3) n' - (4-Chlorobenzylidene) -4- (5- (3, 5-dichlorophenyl) -5- (trifluoromethyl) -4, 5-dihydroisoxazol-3-yl) -2-methylbenzoyl hydrazine:

4- (5- (3, 5-dichlorophenyl) -5- (trifluoromethyl) -4, 5-dihydroisoxazol-3-yl) -2-methylbenzoyl hydrazine (0.209g, 0.5mmol) was charged into a 100mL three-necked round-bottomed flask, 10mL ethanol was added, 4-chlorobenzaldehyde (0.70g, 0.5mmol) was added dropwise, and the reaction was carried out at 85 ℃ for 2 h. After the reaction is finished, the reaction mixture is decompressed and desolventized, the silica gel is stirred, and the white solid of 0.125g is obtained by chromatographic column separation.

Example 39: n' - (4-fluorobenzylidene) -4- (5- (3, 5-dichlorophenyl) -5- (trifluoromethyl) -4, 5-dihydroisoxazol-3-yl) -2-methylbenzoyl hydrazine

4- (5- (3, 5-dichlorophenyl) -5- (trifluoromethyl) -4, 5-dihydroisoxazol-3-yl) -2-methylbenzoyl hydrazine (0.209g, 0.5mmol) was charged into a 100mL three-necked round-bottomed flask, 10mL ethanol was added, 4-fluorobenzaldehyde (0.62g, 0.5mmol) was added dropwise, and the reaction was carried out at 85 ℃ for 2 h. After the reaction, the reaction mixture was desolventized under reduced pressure, stirred with silica gel and separated by a column chromatography to obtain 0.140g of a white solid.

Example 40: n' - (2, 6-Dichlorobenzylidene) -4- (5- (3, 5-dichlorophenyl) -5- (trifluoromethyl) -4, 5-dihydroisoxazol-3-yl) -2-methylbenzoyl hydrazine

(3) n' - (2, 6-Dichlorobenzylidene) -4- (5- (3, 5-dichlorophenyl) -5- (trifluoromethyl) -4, 5-dihydroisoxazol-3-yl) -2-methylbenzoyl hydrazine:

4- (5- (3, 5-dichlorophenyl) -5- (trifluoromethyl) -4, 5-dihydroisoxazol-3-yl) -2-methylbenzoyl hydrazine (0.209g, 0.5mmol) was charged into a 100mL three-necked round-bottomed flask, 10mL ethanol was added, 2, 6-dichlorobenzaldehyde (0.088g, 0.5mmol) was added dropwise, and the reaction was carried out at 85 ℃ for 2 h. After the reaction, the reaction mixture was desolventized under reduced pressure, stirred with silica gel and separated by a column chromatography to obtain 0.159g of a white solid.

Example 41: n' - (4-bromobenzylidene) -4- (5- (3, 5-dichlorophenyl) -5- (trifluoromethyl) -4, 5-dihydroisoxazol-3-yl) -2-methylbenzoyl hydrazine

(3) n' - (4-bromobenzylidene) -4- (5- (3, 5-dichlorophenyl) -5- (trifluoromethyl) -4, 5-dihydroisoxazol-3-yl) -2-methylbenzoyl hydrazine:

4- (5- (3, 5-dichlorophenyl) -5- (trifluoromethyl) -4, 5-dihydroisoxazol-3-yl) -2-methylbenzohydrazide (0.209g, 0.5mmol) was charged into a 100mL three-necked round-bottomed flask, 10mL ethanol was added, 4-bromobenzaldehyde (0.093g, 0.5mmol) was added dropwise, and the reaction was carried out at 85 ℃ for 2 h. After the reaction, the reaction mixture was desolventized under reduced pressure, stirred with silica gel and separated by a column chromatography to obtain 0.165g of a white solid.

Example 42: n' - (3-hydroxybenzylidene) -4- (5- (3, 5-dichlorophenyl) -5- (trifluoromethyl) -4, 5-dihydroisoxazol-3-yl) -2-methylbenzoyl hydrazine

(3) n' - (3-hydroxybenzylidene) -4- (5- (3, 5-dichlorophenyl) -5- (trifluoromethyl) -4, 5-dihydroisoxazol-3-yl) -2-methylbenzoyl hydrazine:

4- (5- (3, 5-dichlorophenyl) -5- (trifluoromethyl) -4, 5-dihydroisoxazol-3-yl) -2-methylbenzoyl hydrazine (0.209g, 0.5mmol) was charged into a 100mL three-necked round-bottomed flask, 10mL ethanol was added, 3-hydroxybenzaldehyde (0.061g, 0.5mmol) was added dropwise, and the reaction was carried out at 85 ℃ for 2 hours. After the reaction, the reaction mixture was desolventized under reduced pressure, stirred with silica gel and separated by a column chromatography to obtain 0.131g of a white solid.

TABLE 1 appearance, yield and melting Point of partial Compounds of formula I

"-" indicates no test

Nuclear magnetic resonance hydrogen spectrum of the compound (A), (B), (C)¹H NMR) and carbon Spectroscopy (¹³C NMR) data are shown in table 2.

TABLE 2 spectroscopic data for some of the compounds of the examples

Bioassay test example 1: and (3) measuring the biological activity of the target compound for indoor control of diamondback moth.

The target compound was dissolved in DMF solution and diluted with distilled water to give a stock solution with a concentration of 1g/L, and then diluted with TW-80 to give test solutions of 100.0, 10.0. mu.g/mL and other concentrations.

Taking a certain size of the white cabbage, putting the white cabbage into the test solution for 15 seconds, taking the white cabbage out, putting the white cabbage into a culture dish, and airing. Selecting healthy 3-year-old early larvae with consistent individual size. 10-20 larvae are inoculated into each culture dish. Each concentration was set to 3 replicates. After the inoculation of the test insect culture dish, the test insect culture dish is put back to the normal breeding environment of the diamondback moth, and the death rate is checked at the corresponding time after the treatment according to the characteristics of the test medicament.

The rice seedlings in the flowerpots are infected by 10 diamondback moths (adults), 2mL of test solution is sprayed, a TW-80 solution containing DMF is used as a blank control, each group is repeated three times, the treated sogatella furcifera is put in a greenhouse (the temperature is 26 +/-2 ℃, the humidity is 85 +/-5%, and the illumination/night is 16/8h) for feeding, and the number of dead insects is recorded after 48 h. Lethality and corrected lethality were calculated as follows, and the activity data is shown in table 3:

lethality rate (number of dead insects)/(total number of treated insects) × 100

Corrected lethality rate (treatment lethality-blank lethality)/(1-blank lethality) × 100

TABLE 3 lethality of the compounds prepared in the examples section to Plutella xylostella

"-" indicates no test

Raw test example 2: and (3) measuring the biological activity of the target compound for indoor control of spodoptera frugiperda.

The target compound was dissolved in DMF solution and diluted with distilled water to give a stock solution with a concentration of 1g/L, and then diluted with TW-80 to give test solutions of 100.0, 10.0. mu.g/mL and other concentrations. 100ul of the corresponding concentration of the medicament is respectively taken and dripped into the prepared feed in advance, and the feed is dried for standby.

Placing 12 Spodoptera frugiperda in the feed, using TW-80 solution containing DMF as blank control, repeating each group for three times, feeding the Spodoptera frugiperda in a greenhouse (temperature 26 + -2 deg.C, humidity 85 + -5%, illumination/night 16/8h), and recording the dead number of insects after 48 h. Lethality and corrected lethality were calculated as follows, and the activity data is shown in table 4:

TABLE 4 lethality of the compounds prepared in the examples section to Spodoptera frugiperda

"-" indicates no test

The insecticidal activity result shows that the compound has certain insecticidal activity, and the insecticidal activity of part of target compounds on spodoptera frugiperda is measured by a membrane method. As can be seen from table 4, most of the compounds had some insecticidal activity. According to the analysis of structure-activity relationship, R⁴When the compound contains fluorine aromatic ring and cyclopropyl, the compound shows better insecticidal activity. Among them, the compounds S1, S3, S10, S13 and S19 had the best activity, and the lethality to plutella xylostella and spodoptera frugiperda was 100% at a concentration of 100. mu.g/mL, and the lethality to spodoptera frugiperda was 100% at a concentration of 10. mu.g/mL for the compounds S1, S3, S13 and S19, respectively.

TABLE 5 LC of Compound L14 against Spodoptera frugiperda₅₀Value (48h)

The insecticidal activity of part of target compounds on spodoptera frugiperda is measured by a feed pharmaco-membrane method (tables 4 and 5), and the result shows that most compounds have certain insecticidal activity. In particular, L14 has 100% lethality to Spodoptera frugiperda at a concentration of 10 mg/L. Further concentration reduction tests show that L14 has excellent insecticidal activity on spodoptera frugiperda and is superior to a control medicament chlorantraniliprole. Preliminary structure-activity relationship research shows that 2-fluorine, 3-fluorine and 4-fluorine have significantly better insecticidal activity on Spodoptera frugiperda than other functional groups.

The foregoing is only a preferred embodiment of the present invention, and it should be noted that, for those skilled in the art, various modifications and decorations can be made without departing from the principle of the present invention, and these modifications and decorations should also be regarded as the protection scope of the present invention.

Claims

1. An isoxazoline hydrazide derivative, or a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, or a solvate thereof, or a prodrug molecule thereof, wherein the structure of the isoxazoline hydrazide derivative is represented by formula (I) or formula (II):

wherein:

Z is selected from O or S.

2. The isoxazoline hydrazide derivative according to claim 1, or a stereoisomer, or a pharmaceutically acceptable salt thereof, or a solvate thereof, or a prodrug molecule thereof,

3. The isoxazoline hydrazide derivative, or a stereoisomer, or a pharmaceutically acceptable salt, or a solvate thereof, or a prodrug molecule thereof according to claim 1 or 2, wherein the isoxazoline hydrazide derivative includes but is not limited to:

4. the method for producing an isoxazoline hydrazide derivative, or a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, or a solvate thereof, or a prodrug molecule thereof according to any one of claims 1 to 3, wherein the hydrazide is produced from an isoxazoline ester and hydrazine hydrate, and the isoxazoline hydrazide derivative is produced by reacting the hydrazide with an acid chloride or an aldehyde.

5. A composition comprising the isoxazoline hydrazide derivative according to any one of claims 1 to 3, or a stereoisomer, or a pharmaceutically acceptable salt, or a solvate thereof, or a prodrug molecule thereof, or the isoxazoline hydrazide derivative prepared by the preparation method according to claim 4, or a stereoisomer, or a pharmaceutically acceptable salt, or a solvate thereof, or a prodrug molecule thereof, and any other active ingredient.

6. The composition of claim 5, which includes, but is not limited to, an insecticide.

7. Formulation comprising a composition according to claim 5 or 6 and acceptable adjuvants or adjuvants.

8. The formulation of claim 7, wherein the formulation comprises one or more of Emulsifiable Concentrate (EC), Dust (DP), Wettable Powder (WP), Granules (GR), Aqueous Solution (AS), Suspension Concentrate (SC), ultra low volume spray (ULV), Soluble Powder (SP), Microcapsule (MC), smoke agent (FU), aqueous Emulsion (EW), water dispersible granules (WG).

9. Use of an isoxazoline hydrazide derivative, or a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, or a solvate thereof, or a prodrug molecule thereof according to any one of claims 1 to 3, the isoxazoline hydrazide derivative prepared by the preparation method according to claim 4, or a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, or a solvate thereof, or a prodrug molecule thereof, the composition according to claim 5 or 6, or the formulation according to claim 7 or 8 for controlling agricultural pests;

10. A method for preventing and controlling agricultural diseases and insect pests is characterized by comprising the following steps: taking the isoxazoline hydrazide derivative, or a stereoisomer, or a pharmaceutically acceptable salt, or a solvate thereof, or a prodrug molecule thereof according to any one of claims 1 to 3, the isoxazoline hydrazide derivative, or a stereoisomer, or a pharmaceutically acceptable salt thereof, or a solvate thereof, or a prodrug molecule thereof prepared by the preparation method according to claim 4, the composition according to claim 5 or 6, or the formulation according to claim 7 or 8, for acting on harmful substances or living environments thereof;