WO2020030095A1 - Pharmaceutical composition containing meta-diamide compound and use thereof - Google Patents

Abstract

A pharmaceutical composition containing a meta-diamide compound and use thereof. The pharmaceutical composition comprises an active ingredient A and an active ingredient B. The active ingredient A is a meta-diamide compound having a structure as shown in formula I, and the active ingredient B comprises any one or a combination of two of other bactericides, insecticides or acaricides. The active ingredient A and the active ingredient B have a synergistic effect, the use amount of the composition is greatly reduced compared with that of an insecticide having a single active ingredient, the control effect is greatly improved, and the control profile is enlarged. Said composition can be applied to various plant diseases and insect pests of crops such as vegetables, fruit trees, flowers, cereals, oil plants and sugar plants as well as those in the field of horticulture and forestry, and can delay the development of drug resistance.

Description

Pharmaceutical composition containing metadiamide compound and application thereof Technical field

The present application belongs to the technical field of pest control compositions, and relates to a pharmaceutical composition containing a metadiamide compound and an application thereof.

Background technique

In the production of crops such as agriculture and horticulture, the damage caused by pests is still very significant. The pests have resistance to existing pesticides and the environment is not friendly to existing pesticides. There has been a need to develop better activity and lower dosages. New environmentally friendly pesticides or pesticide compositions.

For example, CN101208009A discloses that a composition containing a metadiamide compound has an insecticidal effect, and various types of pesticides and fungicides of various structure types in the prior art are widely used in various crops. With the continuous use of pesticides, pests and diseases will become resistant to some existing pesticide products, and the insecticidal activity of existing pesticide varieties may not always meet the needs of many agricultural practices.

Insecticide compositions have an important role in improving the effectiveness of insecticides, expanding the spectrum of control, and delaying the development of resistance. Therefore, in the art, it is still desirable to develop more efficient pesticide compositions to meet the needs of agriculture and the forestry industry.

Summary of the invention

Aiming at the problems existing in the prior art, the purpose of the present application is to provide a pharmaceutical composition containing an m-diamide compound and its application. The pharmaceutical composition has a synergistic effect, and can prevent and control diseases caused by pests and diseases. A variety of agricultural and forestry pests and diseases.

To achieve this, the following technical solutions are used in this application:

In one aspect, the present application provides a pharmaceutical composition containing an m-diamide compound. The pharmaceutical composition includes an active ingredient A and an active ingredient B. The active ingredient A is an amide compound having a structure represented by Formula I. The active ingredient B includes any one or a combination of two other fungicides, insecticides or acaricides;

Wherein Z is selected from hydrogen, fluorine, chlorine, bromine, iodine, cyano, nitro, hydroxyl, substituted or unsubstituted 3-10 membered heterocyclic group, C ₁ -C ₆ alkyl, C ₁ -C ₆ haloalkane , C ₁ -C ₆ alkoxy, C ₁ -C ₆ haloalkoxy, C ₁ -C ₆ alkylsulfinyl, C ₁ -C ₆ haloalkylsulfinyl, C ₁ -C ₆ alkylsulfonyl Acyl or C ₁ -C ₆ haloalkylsulfonyl; Q is selected from C ₃ -C ₈ cycloalkyl or C ₃ -C ₈ halocycloalkyl; X is selected from hydrogen, fluorine or trifluoromethyl; Y _{1 is} selected From fluorine, chlorine, bromine, iodine, cyano, nitro, C ₁ -C ₆ alkyl, C ₁ -C ₆ haloalkyl, C ₁ -C ₆ haloalkoxy, C ₂ -C ₄ alkenyl, C ₂ -C ₄ haloalkenyl, C ₂ -C ₄ alkynyl, C ₂ -C ₄ haloalkynyl, C ₃ -C ₈ cycloalkyl, C ₃ -C ₈ halocycloalkyl, C ₁ -C ₆ alkylcarbonyl, C ₁ -C ₆ alkylsulfinyl, C ₁ -C ₆ haloalkylsulfinyl, C ₁ -C ₆ alkylsulfonyl or C ₁ -C ₆ haloalkylsulfonyl; Y ₂ selected From chlorine, bromine, iodine, cyano, nitro, C ₁ -C ₆ haloalkyl, C ₁ -C ₆ haloalkoxy, C ₂ -C ₄ alkenyl, C ₂ -C ₄ haloalkenyl, C ₂ -C ₄ alkynyl, C ₂ -C ₄ haloalkynyl, C ₃ -C ₈ cycloalkyl, C ₃ -C ₈ Generation cycloalkyl, C ₁ -C ₆ alkylcarbonyl, C ₁ -C ₆ alkylsulfinyl, C ₁ -C ₆ haloalkylsulfinyl group, C ₁ -C ₆ alkylsulfonyl or C ₁ -C ₆ haloalkylsulfonyl; R _{1 is} selected from hydrogen, fluorine or methoxy; R _{2 is} selected from fluorine or trifluoromethyl; R ₃ and R ₄ are each independently selected from hydrogen, halogen, cyano, nitro, C _1- C ₆ alkyl, C ₁ -C ₆ haloalkyl, C ₃ -C ₈ cycloalkyl or C ₃ -C ₈ halocycloalkyl; m represents an integer from 0 to 5; n represents an integer from 0 to 3 ; W ₁ and W _{2 are} independently an oxygen atom or a sulfur atom.

The pharmaceutical composition using the m-bisamide compound having the structure shown by the formula I as described in the present application as the active ingredient A and blended with the active ingredient B has a synergistic effect between the active ingredient A and the active ingredient B. On the one hand, It can reduce the use of a single active ingredient, on the other hand, the control effect is significantly improved, and because the active ingredient A can reach more than 90% of the insecticidal activity at a low dose, the effect is fast, and the insecticidal activity can be exerted after one day of application It can achieve high insecticidal activity within 3 days, and has good fast-acting properties, so that the pharmaceutical composition containing it also has good fast-acting properties, and because the effect is good at low doses, reducing the concentration of the drug is too large. Damage to plants and humans, and less drug residues during application, which is more conducive to environmental protection.

Preferably, the heterocyclic group is selected from oxadiazolyl, oxazolyl, isoxazolyl, isoxazoline, pyrazolyl, pyrazoline, furanyl, thienyl, pyridyl, pyrimidinyl , Pyridazinyl, pyrazinyl, benzoxazolyl, benzothiazolyl, benzimidazolyl, benzothiadiazolyl, quinolinyl, isoquinolinyl, quinoxaline, or quinazoline.

In the present application, the 3-10 membered heterocyclyl group substituted by R ₅ substituted 3-10 membered heterocyclyl, said R ₅ is selected from hydrogen, halo, cyano, nitro, C ₁ -C ₆ alkyl, C ₁ -C ₆ haloalkyl, C ₁ -C ₆ alkoxy or C ₁ -C ₆ haloalkoxy.

In the m-bisamide compound represented by formula I in the present application, when m Z groups connected to a benzene ring, when m is greater than 1, a plurality of Z groups may be the same or different. Similarly, when the substituent X on the benzene ring is greater than 1, multiple X groups may be the same or different.

In the present application, as a preferred technical solution, in Formula I,

Z is selected from hydrogen, fluorine, chlorine, bromine, iodine, cyano, nitro, hydroxy, 3-10 membered heterocyclic group, 3-10 membered heterocyclic group substituted with at least one R ₅ , C ₁ -C ₆ Alkyl, C ₁ -C ₆ haloalkyl, C ₁ -C ₆ alkoxy, C ₁ -C ₆ haloalkoxy, C ₁ -C ₆ alkylsulfinyl, C ₁ -C ₆ haloalkylsulfinyl , C ₁ -C ₆ alkylsulfonyl or C ₁ -C ₆ haloalkylsulfonyl; Q is selected from C ₃ -C ₈ cycloalkyl or C ₃ -C ₈ halocycloalkyl; X is selected from hydrogen or fluorine ; Y _{1 is} selected from fluorine, chlorine, bromine, iodine, cyano, nitro, C ₁ -C ₆ alkyl, C ₁ -C ₆ haloalkyl, C ₁ -C ₆ haloalkoxy; Y _{2 is} selected from chlorine, Bromine, iodine, cyano, nitro, C ₁ -C ₆ alkyl, C ₁ -C ₆ haloalkyl, C ₁ -C ₆ haloalkoxy C ₁ -C ₆ alkylcarbonyl, C ₁ -C ₆ alkyl Sulfinyl, C ₁ -C ₆ haloalkylsulfinyl, C ₁ -C ₆ alkylsulfonyl or C ₁ -C ₆ haloalkylsulfonyl; R _{1 is} selected from hydrogen, fluorine or methoxy; R _{2 is} selected From fluorine or trifluoromethyl; R ₃ and R ₄ are each independently selected from hydrogen, halogen, cyano, nitro, C ₁ -C ₆ alkyl, C ₁ -C ₆ haloalkyl, C ₃ -C ₈ ring alkyl or C ₃ -C ₈ halocycloalkyl group; R ₅ is selected from , Halo, cyano, nitro, C ₁ -C ₆ alkyl, C ₁ -C ₆ haloalkyl, C ₁ -C ₆ alkoxy or C ₁ -C ₆ haloalkoxy group; m represents an integer of 0 to 5, N represents an integer of 0 to 3; W ₁ and W _{2 are} independently an oxygen atom or a sulfur atom.

In this application, as another preferred technical solution, in Formula I, Z is selected from hydrogen, fluorine, chlorine, bromine, iodine, cyano, nitro, hydroxyl, methoxy, methyl, trifluoromethyl, penta Fluoroethyl, heptafluoroisopropyl, difluoromethoxy, trifluoromethoxy, methylsulfinyl, trifluoromethylsulfinyl, methanesulfonyl, trifluoromethanesulfonyl, or 5-trifluoro Methyl-1,2,3-thiadiazol-3-yl; m represents an integer from 0 to 5; Q is selected from cyclopropyl, 1-chlorocyclopropyl, 1-fluorocyclopropyl, cyclobutyl group, cyclopentyl, cyclohexyl, cycloheptyl or cyclooctyl; X is selected hydrogen; Y ₁ selected from bromo, iodo, trifluoromethyl, pentafluoroethyl, heptafluoroisopropyl group, or a trifluoromethanesulfonyloxy Oxygen; Y _{2 is} selected from the group consisting of chlorine, bromine, iodine, cyano, nitro, methyl, ethyl, isopropyl, tert-butyl, acetyl, trifluoroacetyl, propionyl, isopropylamide, trifluoro Methyl, pentafluoroethyl, heptafluoroisopropyl, trifluoromethoxy, methylsulfinyl, trifluoromethylsulfinyl, methanesulfonyl or trifluoromethanesulfonyl; R _{1 is} selected from hydrogen, fluoro or methoxy; R ₂ is selected from fluoro; R ₃ and R ₄ are each independently selected from hydrogen, fluoro, chloro, bromo, iodo Cyano, nitro, methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, tert-butyl, n-pentyl, 2-pentyl, neopentyl, isopentyl, 4 -Methyl-2-pentyl, n-hexyl, monofluoromethyl, difluoromethyl, trifluoromethyl, monochloromethyl, dichloromethyl, trichloromethyl, pentafluoroethyl, heptafluoroiso Propyl, cyclopropyl, cyclobutyl, cyclopentyl, perfluorocyclopropyl, perfluorocyclobutyl or perfluorocyclopentyl; W ₁ and W ₂ are oxygen atoms.

As a further preferred technical solution of the present application, the m-diamide compound is any one of the compounds shown in Table 1 below having the general formula I.

Table 1

Where H is a hydrogen atom, F is a fluorine atom, Cl is a chlorine atom, Br is a bromine atom, I is an iodine atom, CN is a cyano group, NO _{2 is a} nitro group, Me is a methyl group, OMe is a methoxy group, and CHCl ₂ Is dichloromethyl, CH ₂ Cl is monochloromethyl, CCl ₃ is trichloromethyl, CHF ₂ is difluoromethyl, CH ₂ F is monofluoromethyl, CF ₃ is trifluoromethyl, OCF ₃ Is trifluoromethoxy, c-Pr is cyclopropyl, c-Bu is cyclobutyl, c-Pent is cyclopentyl, c-Hex is cyclohexyl, in the group

Represents the group attachment position. The number in front of the substituent represents the position of the substituent on the benzene ring. For example, 4-trifluoromethoxy represents the 4-position of trifluoromethoxy on the benzene ring, and 4-cyano represents the cyano group on the benzene ring. Position, 2,3-difluoro represents two fluorine atoms in the 2 and 3 positions of the benzene ring, and 3,4-difluoro represents two fluorine atoms in the 3 and 4 positions of the benzene ring, respectively. .

Preferably, in formula I, Z is selected from hydrogen, fluorine, chlorine, bromine, iodine, cyano, nitro, trifluoromethyl, pentafluoroethyl, heptafluoroisopropyl, difluoromethoxy, tris Fluoromethoxy, methylsulfinyl, trifluoromethylsulfinyl, methanesulfonyl or trifluoromethanesulfonyl; m represents an integer from 0 to 5, and Q is selected from cyclopropyl 1-chlorocyclopropyl ; Y _{1 is} selected from bromine or iodine; Y _{2 is} selected from bromine, methyl, isopropyl, tert-butyl, acetyl, trifluoromethyl or trifluoromethoxy; R _{1 is} selected from hydrogen, methoxy or Fluorine; R _{2 is} selected from fluorine; R ₃ and R ₄ are each independently selected from hydrogen, chlorine, methyl, monochloromethyl, trifluoromethyl or cyclopropyl, and W ₁ and W ₂ are oxygen atoms.

In this application, as a more preferred technical solution, the m-diamide compound is any one or a combination of at least two selected from the following compounds:

The alkyl group in the present application refers to a straight or branched chain form, such as methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, n-pentyl, Isoamyl, n-hexyl and other groups. Haloalkyl refers to a group in which an alkyl group is substituted with one or more halogen atoms. The alkoxy group refers to a group having an oxygen atom at the terminal end of the alkyl group, such as methoxy, ethoxy, n-propoxy, isopropoxy, tert-butoxy and the like. Haloalkoxy refers to a group in which an alkoxy group is substituted with one or more halogen atoms. Halogen is F, Cl, Br or I.

The term "C1-C6 alkyl" as used herein refers to a straight or branched chain alkyl group having 1 to 6 carbon atoms, and includes, but is not limited to, methyl, ethyl, n-propyl, isopropyl, and n-butyl Base, isobutyl, sec-butyl, tert-butyl, n-pentyl, isopentyl, n-hexyl and the like. The term "C1-C6 alkoxy" refers to a straight or branched chain alkoxy group having 1 to 6 carbon atoms and includes, without limitation, methoxy, ethoxy, n-propoxy, isopropoxy And terbutoxy. "C1-C6 haloalkyl" refers to a linear or branched alkyl group having 1 to 6 carbon atoms substituted with a halogen atom, and includes, without limitation, trifluoromethyl, difluoromethyl, 1,1,1- Trifluoroethyl, pentafluoroethyl, heptafluoron-propyl, heptafluoroisopropyl and the like. The term "C3-C8 cycloalkyl" as used herein refers to a cyclic alkyl group having 3 to 8 carbon atoms on the ring, and includes, without limitation, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, Cycloheptyl, cyclooctyl, etc. The term "C3-C8 halocycloalkyl" as used herein refers to a cyclic alkyl group having 3 to 8 carbon atoms substituted with halogens on the ring, and includes, without limitation, 1-chlorocyclopropyl, 1- Fluorocyclopropyl, perfluorocyclopropyl, 1-chlorocyclobutyl, 1-chlorocyclopentyl and the like.

In this application, C1-C6, C3-C8, etc. before the specific group indicate the number of carbon atoms contained in the group, for example, C1-C6 indicates that the number of carbon atoms can be 1, 2, 3, 4, 5 Or 6 groups, C3-C8 represents a group with 3, 4, 5, 6, 7, or 8 carbon atoms, C2-C4 represents a group with 2, 3, or 4 carbon atoms, etc. And so on.

In addition, in this application, "i-" means iso, "s-" means secondary, "t-" means tertiary, "Me" means methyl, "Et" means ethyl, and "i-Pr""Meansisopropyl," c-Pr "means cyclopropyl," c-Bu "means cyclopropyl," c-Pent "means cyclopentyl," c-Hex "means cyclohexyl, and" t-Bu " Represents tert-butyl, "CF ₃ " represents trifluoromethyl, "OCF ₃ " represents trifluoromethoxy, "methanesulfonyl" represents difluoromethoxy, "H" represents a hydrogen atom, and "F" represents fluorine Atom, "Cl" represents a chlorine atom, "Br" represents a bromine atom, "I" represents an iodine atom, "O" represents an oxygen atom, "S" represents a sulfur atom, "Ac" represents an acetyl group, and "OMe" represents a methoxy group "OEt" means ethoxy, "O- (i-Pr)" means isopropoxy, "OCF ₃ " means trifluoromethoxy, "-CN" means cyano, and "-NO ₂ " means Nitro.

The compound of the general formula I of the present application can be prepared by the following method. Unless otherwise noted, each group in the reaction formula has the same definition as above.

Preparation method 1:

The structure of the compound of the general formula I of the present application is as follows, which can be prepared by the following method:

Among them, LG is selected from fluorine, chlorine, bromine, C ₁ -C ₁₂ alkoxy, C ₁ -C ₁₂ alkylacyl or C ₁ -C ₁₂ alkylacyloxy; R ₁ , R ₂ , R ₃ , R _{4, Y 1, Y 2,} Q, W 1, W 2, X, Z, m, n is the same as defined above, are not repeated here.

1- (i): A compound of the general formula III is reacted with a compound of the general formula IV to obtain a compound of the general formula V.

Preferably, the molar ratio of the compound of the general formula III to the compound of the general formula IV is 0.5-2: 1, for example, 0.5: 1, 0.8: 1, 1: 1, 1.2: 1, 1.4: 1, 1.5: 1, 1.8 : 1 or 2: 1.

In the present application, the reaction described in step 1- (i) is performed in the presence of a basic substance, which is an organic base and / or an inorganic base.

Preferably, the organic base is triethylamine, N, N-diisopropylethylamine, N, N-dimethylaniline, pyridine, sodium carbonate, potassium carbonate, sodium methoxide, sodium ethoxide, sodium tert-butoxide Or any one or a combination of at least two of potassium tert-butoxide.

Preferably, the inorganic base is any one or a combination of at least two of sodium hydroxide, potassium hydroxide or sodium hydride.

Preferably, the solvent for the reaction in step 1- (i) is selected from the group consisting of dichloromethane, chloroform, toluene, ethyl acetate, acetone, acetonitrile, tetrahydrofuran, dioxane, N, N-dimethylformamide, di Any one or a combination of at least two of methyl sulfoxide or hexamethylphosphoryl triamine.

Preferably, the temperature of the reaction in step 1- (i) is greater than or equal to room temperature and less than or equal to the boiling point of the reaction solvent, such as 25 ° C, 30 ° C, 35 ° C, 40 ° C, 45 ° C, 50 ° C, 60 ° C, 70 ° C. , 75 ° C, 80 ° C, 85 ° C, 90 ° C, etc., or the reaction is carried out at the boiling point of the solvent, that is, under reflux.

Preferably, the reaction time in step 1- (i) is 0.5-48 hours, such as 0.5 hours, 1 hour, 3 hours, 5 hours, 8 hours, 10 hours, 12 hours, 15 hours, 18 hours, 20 hours , 23 hours, 25 hours, 28 hours, 30 hours, 33 hours, 35 hours, 38 hours, 40 hours, 44 hours, or 48 hours.

1- (ii): A compound of the general formula V is reacted with a compound of the general formula VI to obtain a compound of the general formula VII.

Preferably, the molar ratio of the compound of general formula V to the compound of general formula VI is 0.5-2: 1, for example, 0.5: 1, 0.8: 1, 1: 1, 1.2: 1, 1.4: 1, 1.6: 1, 1.8 : 1 or 2: 1.

In the present application, the reaction described in step 1- (ii) is performed in the presence of a basic substance, which is an organic base and / or an inorganic base.

Preferably, the organic base is triethylamine, N, N-diisopropylethylamine, N, N-dimethylaniline, pyridine, sodium carbonate, potassium carbonate, sodium methoxide, sodium ethoxide, sodium tert-butoxide Or any one or a combination of at least two of potassium tert-butoxide.

Preferably, the inorganic base is any one or a combination of at least two of sodium hydroxide, potassium hydroxide or sodium hydride.

Preferably, the solvent for the reaction in step 1- (ii) is selected from the group consisting of dichloromethane, chloroform, toluene, ethyl acetate, acetonitrile, tetrahydrofuran, dioxane, N, N-dimethylformamide, dimethyl Any one or a combination of at least two of sulfoxide or hexamethylphosphoryltriamine.

Preferably, the reaction temperature in step 1- (ii) is greater than or equal to -10 ° C and less than or equal to the boiling point of the reaction solvent, such as -10 ° C, -5 ° C, 0 ° C, 5 ° C, 10 ° C, 15 ° C, 20 The reaction is carried out at a temperature of 25 ° C, 25 ° C, 30 ° C, 35 ° C, 40 ° C, 45 ° C, 50 ° C, 60 ° C, 70 ° C, 75 ° C, 80 ° C, 85 ° C, 90 ° C, or the boiling point of the solvent, which is the reflux state.

Preferably, the reaction time in step 1- (ii) is 0.5-48 hours, such as 0.5 hours, 1 hour, 3 hours, 5 hours, 8 hours, 10 hours, 12 hours, 15 hours, 18 hours, 20 hours , 23 hours, 25 hours, 28 hours, 30 hours, 33 hours, 35 hours, 38 hours, 40 hours, 44 hours, or 48 hours.

1- (iii): A compound of the general formula VII is hydrolyzed to obtain a compound of the general formula VIII.

The hydrolysis in step 1- (iii) is performed in any one or a mixed solvent of at least two of water, methanol, ethanol, tetrahydrofuran or dioxane.

Preferably, the hydrolysis in step 1- (iii) is performed in the presence of a basic substance, which is preferably lithium hydroxide, sodium hydroxide or potassium hydroxide.

Preferably, the amount of the basic substance is 1-5 times the molar amount of the compound of the general formula VII, for example, 1 times, 1.3 times, 1.5 times, 1.8 times, 2 times, 2.5 times, 3 times, 3.5 times, and 4 times. , 4.5 times or 5 times.

1- (iv): A compound of the general formula VIII is subjected to a substitution reaction to obtain a compound of the general formula II.

In this step, a compound of the general formula VIII and a compound containing an LG group such as thionyl chloride, oxalyl chloride, phosgene, phosphoryl chloride, phosphorus pentachloride, phosphorus trichloride, and thionyl bromide are known by a known method. , Triphosgene, phosphorus tribromide or isopropyl chloroformate, etc., to prepare a compound represented by general formula II.

1- (v): Compound of general formula II reacts with compound of general formula IX to obtain compound of general formula I

Preferably, the molar ratio of the compound of the general formula II to the compound of the general formula IX is 0.5-2: 1, for example, 0.5: 1, 0.8: 1, 1: 1, 1.2: 1, 1.4: 1, 1.6: 1, 1.8 : 1 or 2: 1.

In the present application, the reaction described in step 1- (v) is performed in the presence of a basic substance, which is an organic base and / or an inorganic base.

Preferably, the organic base is trimethylamine, triethylamine, diisopropylethylamine, tri-n-butylamine, pyridine, piperidine, 3-methylpyridine, 2,6-dimethyl Any one or a combination of at least two of pyridine, N-methylmorpholine, 3-methylimidazole, 4-N, N-dimethylaminopyridine, an alkali metal alcoholate, and lithium amine.

Preferably, the alkali metal alcoholate is sodium methoxide and / or sodium ethoxide. Preferably, the lithium amino is lithium diisopropylamide.

Preferably, the inorganic base is any one or a combination of at least two of alkali metal hydroxides, carbonates or phosphates.

Preferably, the alkali metal hydroxide is any one or a combination of at least two of lithium hydroxide, sodium hydroxide, or potassium hydroxide. Preferably, the carbonate is any one or a combination of at least two of sodium bicarbonate, sodium carbonate or potassium carbonate. Preferably, the phosphate is dipotassium hydrogen phosphate and / or trisodium phosphate.

Preferably, the solvent of the reaction in step 1- (v) is a halogenated hydrocarbon, an aromatic hydrocarbon, a chain or cyclic ether, an ester, a ketone, a nitrile or an aprotic polar inert solvent. Any one or a combination of at least two.

Preferably, the halogenated hydrocarbon is any one or a combination of at least two of dichloromethane, chloroform, or carbon tetrachloride. Preferably, the aromatic hydrocarbon is any one or a combination of at least two of benzene, toluene, xylene, chlorobenzene or dichlorobenzene. Preferably, the chain or cyclic ethers are any one or a combination of at least two of diethyl ether, tetrahydrofuran, dioxane, or 1,2-dimethoxyethane. Preferably, the ester is ethyl acetate and / or butyl acetate. Preferably, the ketone is any one or a combination of at least two of acetone, methyl isobutyl ketone and cyclohexanone. Preferably, the nitriles are acetonitrile and / or propionitrile. Preferably, the aprotic polar inert solvent is 1,3-dimethyl-2-imidazolinone, sulfolane, dimethylsulfoxide, N, N-dimethylformamide, N-methylpyrrolidone, Any one or a combination of at least two of N, N-dimethylacetamide or hexamethylphosphoramide.

Preferably, the reaction temperature in step 1- (v) is -70 ° C or more and the boiling point of the reaction solvent, for example, -70 ° C, -50 ° C, -30 ° C, -10 ° C, -5 ° C, 0 ℃, 15 ℃, 25 ℃, 30 ℃, 35 ℃, 40 ℃, 45 ℃, 50 ℃, 60 ℃, 70 ℃, 75 ℃, 80 ℃, 85 ℃, 90 ℃, etc. Perform the reaction.

Preferably, the reaction time in step 1- (v) is 0.5-48 hours, such as 0.5 hours, 1 hour, 3 hours, 5 hours, 8 hours, 10 hours, 12 hours, 15 hours, 18 hours, 20 hours , 23 hours, 25 hours, 28 hours, 30 hours, 33 hours, 35 hours, 38 hours, 40 hours, 44 hours, or 48 hours.

Preparation method 2:

The compound of the general formula I of the present application can be prepared by another method as follows:

Among them, the definitions of R ₁ , R ₂ , R ₃ , R ₄ , Y ₁ , Y ₂ , QW ₁ , W ₂ , X, Z, m, n, and LG are the same as above, and are not repeated here.

2- (i): Halogenation of a compound of general formula X to obtain a compound of general formula XI

That is, in this step, a compound of the general formula X and thionyl chloride, oxalyl chloride, phosgene chloride, phosphoryl chloride, phosphorus pentachloride, phosphorus trichloride, thionyl bromide, triphosgene, and tribromide are made by a known method in this step. Phosphoride, isopropyl chloroformate and the like are reacted to prepare a compound represented by the general formula XI containing an LG group.

2- (ii): A compound of the general formula XI is reacted with a compound of the general formula IX to obtain a compound of the general formula XII.

The compound represented by the general formula XI is reacted with the compound represented by the general formula IX under the same conditions as described in 1- (v) to prepare a compound represented by the general formula XII.

2- (iii): Compound of general formula XII is reduced to obtain compound of general formula XIII

The aromatic carboxylic acid amide derivative having a nitro group represented by the general formula XII can be reduced to produce an aromatic carboxylic acid amide derivative having an amine group represented by the general formula XIII.

Examples of the reduction reaction include a method using a hydrogenation reaction and a method using a metal compound (such as stannous chloride) or a metal (zinc powder, iron powder, etc.).

The hydrogenation reaction method can be used in a suitable solvent in the presence of a catalyst, under normal pressure or under pressure, in a hydrogen atmosphere. Examples of the catalyst in the hydrogenation reaction include palladium catalysts such as palladium-carbon, cobalt catalysts, ruthenium catalysts, and platinum catalysts. Examples of the solvent include alcohols such as methanol and ethanol; aromatic hydrocarbons such as benzene and toluene; chain or cyclic ethers such as diethyl ether and tetrahydrofuran; and esters such as ethyl acetate.

Preferably, the pressure of the hydrogenation reaction is 0.1-10 MPa, for example, 0.1 MPa, 0.5 MPa, 0.8 MPa, 1 MPa, 1.5 MPa, 2 MPa, 3 MPa, 4 MPa, 5 MPa, 6 MPa, 7 MPa, 8 MPa, 9 MPa, or 10 MPa.

Preferably, the temperature of the hydrogenation reaction is -20 ° C or higher and the boiling point of the reaction solvent, for example, -20 ° C, -10 ° C, -5 ° C, 0 ° C, 5 ° C, 10 ° C, 15 ° C, or 20 ° C. , 25 ° C, 30 ° C, 35 ° C, 40 ° C, 45 ° C, 50 ° C, 60 ° C, 70 ° C, 75 ° C, 80 ° C, etc., or the reaction is carried out at the boiling point of the solvent, which is the reflux state.

Preferably, the time of the hydrogenation reaction is 0.5-48 hours, such as 0.5 hours, 1 hour, 3 hours, 5 hours, 8 hours, 10 hours, 12 hours, 15 hours, 18 hours, 20 hours, 23 hours, 25 Hours, 28 hours, 30 hours, 33 hours, 35 hours, 38 hours, 40 hours, 44 hours, or 48 hours.

Preferably, the method using a metal compound or a metal is performed in any one or a mixed solvent of at least two of methanol, ethanol, or ethyl acetate.

Preferably, the metal compound is stannous chloride, and the metal is any one or a combination of at least two of zinc powder or iron powder.

Preferably, the reaction temperature of the method using a metal compound or a metal is -10 ° C or more and the boiling point of the reaction solvent, for example, -10 ° C, -5 ° C, 0 ° C, 5 ° C, 10 ° C, The reaction is performed at 15 ° C, 20 ° C, 25 ° C, 30 ° C, 35 ° C, 40 ° C, 45 ° C, 50 ° C, 60 ° C, 70 ° C, 75 ° C, 80 ° C, or the boiling point of the solvent, ie, under reflux.

Preferably, the reaction time of the method using a metal compound or a metal is 0.5-48 hours, for example, 0.5 hours, 1 hour, 3 hours, 5 hours, 8 hours, 10 hours, 12 hours, 15 hours, 18 hours, 20 hours, 23 hours, 25 hours, 28 hours, 30 hours, 33 hours, 35 hours, 38 hours, 40 hours, 44 hours, or 48 hours.

2- (ix): A compound of the general formula XIII is reacted with a compound of the general formula IV to obtain a compound of the general formula XIV.

A compound represented by the general formula XIII is reacted with a compound represented by the general formula IV under the same conditions as described in Step 1- (i) to prepare a compound represented by the general formula XII.

2- (v): A compound of the general formula XIV is reacted with a compound of the general formula VI to obtain a compound of the general formula I.

The compound represented by the general formula XIV and the compound represented by the general formula VI are reacted under the same conditions as described in Step 1- (ii) to prepare a compound represented by the general formula XII.

Preferably, the active ingredient B is selected from any one or a combination of at least two fungicides, insecticides or acaricides currently available.

Preferably, the active ingredient B is selected from the group consisting of nicotine, rotenone, veratridine, matrine, dermatol, mineral oil, imazapyr, thiamethoxam, imidacloprid, clothianidin, clothianidin, and pyrimidine Insecticides, nitenpyram, dimethoxam, piperididin, chlorothiline, flufenamid, flufenamid, triflumezopyrim, flupyradifurone (chemical name 4-[(6- Chloro-3-pyridylmethyl) (2,2-difluoroethyl) amino] -furan-2 (5H) one), spinosad, ethyl spinosad, chlorpyrifos, methyl chlorpyrifos, dimethoate, Dimethoate, Dichlorvos, Triazophos, Phoxim, Thiazophos, Diazphos, Malathion, Methamidophos, Hydrazine, Fethion, Paramephos, Promethaphos, Sulfur Dan, chloranthrene, cigawe, bupropion, bupropion, prothiocarb, metronidazole, aphid, aldicarb, neuracarb, thiodicarb, methiocarb, menadicarb, Isoprocarb, secbutacarb, fipronil, fipronil, ethiprole, permethrin, cyfluthrin, dexfenfluthrin, tetrafluthrin, tetrafluthrin, Deltamethrin, cypermethrin, cis-cypermethrin, Z- Cypermethrin, lambda cyhalothrin, fenvalerate, fenvalerate, deltamethrin, tefluthrin, cypermethrin, bifenthrin, allethrin, permethrin, alkyne Promethrin, Fluthrin, Fenvalerate, S-Fenvalerate, Fenvalerate, Permethrin, Fenvalerate, Permethrin, Bicythrin, Refined Bicythrin, Pyrethrin Avermectin, avermectin, avermectin benzoate, pyriproxyfen, phenoxycarb, pymetrozine, tetrabenazine, thiazinone, thiamethoxone, ethiprole, flufenox, lice Mite urea, fluorophenylurea, fluazinam, diflubenzuron, butyl ether urea, chlorpromil, halfenuron, fluoxuron, fenflubenzuron, cyclic carbazide, methoxyfenozide, fenzozide, Furan hydrazide, pyraclostrobin, fenaquinone, nitraclopyr, acetazol, fenflufen, bifenazate, pyraclostrobin, pyraclostrobin, pyraclostrobin, pyraclostrobin, fluorine Acarid, diclofenac, bromofen, triazotin, phentermin, dimethylformamide, pyraclostrobin, indoxacarb, cyanfludizone, spirotetramat, spirotetramat, spiropidion (chemical Name: 3- (4-chloro-2,6-dimethylbenzene ) -8-methoxy-1-methyl-2-oxo-1,8-diazaspiro [4.5] dec-3-en-4-ylethyl carbonate), chlorantraniliprole, fluorine Bentamol, Bromocyanide, Cyclophram, Tetrachloropyramid, Tetraniliprole, Insecticidal, Insecticidal, Fenitrothion, Azadirachtin, Bacillus thuringiensis, Bacillus robustus, Bacillus sphaericus, Acetyl mite Tetra, Tetraacetaldehyde, isocycloseram (chemical name: 4- [5- (3,5-dichloro-4-fluorophenyl) -4,5-monohydro-5- (trifluoromethyl) -3- Isoxazolyl] -N- (2-ethyl-3-oxo-4-isoxazolidinyl) 2-methylbenzamide), tyclopyrazoflor (chemical name: N- [3-chloro-1- ( 3-pyridyl) -1H-pyrazol-4-yl] -N-ethyl-3-[(3,3,3-trifluoropropyl) thio] propanamide), flupyrimin (chemical name: N- ((E) -1- (6-chloro-3-pyridylmethyl) pyridine-2 (1H) -subunit] -2,2,2-trifluoroacetamide), oxazosulfyl (chemical name: 2- [3 -(Ethylsulfonyl) -2-pyridyl] -5-[(trifluoromethyl) sulfonyl] benzoxazole), benzpyrimoxan (5- (1,3-dioxan-2-yl)- 4- [4- (trifluoromethyl) benzyloxy] pyrimidine), fluazaindolizine, fluxametamide, dicloromezotiaz (dichlorothiapyrimidine), t ioxazafen (chemical name: 3-phenyl-5- (thiophen-2-yl) -1,2,4-oxadiazole), fluensulfone (bifluorosulfone), fluhexafon, pyrifluquinazon, prothioconazole, anisole methyl Cycloconazole, fluconazole, enazol, nitrilazole, flusilazole, fenconazole, tebuconazole, hexaconazole, acetonitrile, penconazole, propiconazole, tetrafluoroetherazole, triazole Alcohol, biphenyltriazole, triazolone, azoxystrobin, azoxystrobin, trisoxystrobin, picoxystrobin, pyrazoxystrobin, fluoxastrobin, trisoxystrobin, syringaresin, dimethoxan Oxystrobin, fenoxystrobin, pyraclostrobin, metalaxyl, metalaxyl, fluamide, thiafuramide, bifenapram, fluoxastrobin, fenpropenazole, fluoxastrobin , Fluoxastrobin, fluoxastrobin, pyraclostrobin, fluoxanil, flufenamid, valprocarb, thiazolamide, dimethylam, pyraclostrobin, fluoxazim, Rice blast amide, veracol, fluthiazolyl ethyl ketone, thiabendazole, bacterazole, prochloraz, rice blast ester, nitrile cream, fluconazole, humilis, allocarbazone, ethizob , Clotridime, sclerotia, carbendazim hydrochloride, etimicarb, Carbendazim, benomyl, methylthiocarbam, Jinggangmycin, zotocin, streptomycin sulfate, polyoxin, kasugamycin, wuningmycin, mycoxalol, metalaxyl, Dimethomorph, flumorph, tridemorpholine, azoxystromine, pyrimidin, acetaminophen, dicyananthraquinone, Daisenlian, Formex, Zinc and Zinc, Zinc Zinc, diphosphine, aluminum triethylphosphonate, chlorothalonil, rice blast spirit, tricyclazole, pentachloronitrobenzene, carbostyronitrile, flupronil, sodium disulfonate, fluazinam, copper thiazole, Any one or a combination of at least two of potassium dihydrogen phosphate, sulfur, copper hydroxide, activated ester, or flurazole activated ester.

Wherein, when the active ingredient A is selected from the following compounds,

B is not selected from the group consisting of avermectin, methylaminoavermectin benzoate, spinosyn, ethyl spinosad, ivermectin, mibemycin, thiamethoxam, imidacloprid, clothianidin, Clothianidin, acetamiprid, nitenpyram, dipyridam, epoxipyram, flupurone, flufenacil, nitrflufenid, pymetrozine, thiazidone, trifluorobenzimid , Dichlorothiapyrimidine, diprofen, pyrifluquinazon, benzpyrimoxan, anisoleconazole, tebuconazole, prothioconazole, cyclopropazol, azoxystrobin, oxystrobin, pyraclostrobin , Picoxystrobin, metalaxyl, metalaxyl, flupronil, prochloraz, cyprodin, polyoxin, Jinggangmycin, kasugamycin, zotocin, thiamethoxam, Imidacloprid, clothianidin, clothianidin, acetamiprid, nitenpyram, diflubenzuron, epoxifen, flupyramid, flubendicarb, flubendicarb, acetamiprid, thiamethoxam Ketones, trifluorobenzimid, dichlorothiapyrimidine, diprofen, pyrifluquinazon, benzpyrimoxan, anisole, tebuconazole, tebuconazole, prothioconazole, cyclopropazol, azoxystrobin, oxystrobin , Fenoxystrobin, picoxystrobin, metalaxyl, metalaxyl, flupronil, prochloraz, cyprodin, chlorantraniliprole, flubendiamide, bromocyanid, tetrachloro Intrapyramid, Tetrabenpyramid, Chlorflufenamid, Cyclofazone, Fluoxazolamide, Fipronil, Acetofen, Acetoniprole, Indoxacarb, Tetrabenzuron, Tetrabenzuron, Tebufenac Carbendiamide, chlorfenuron, methoxid, acetamiprid, chlorpyrifos, acephate, phoxim, dichlorvos, fenthion, fenprofen, triazophos, beta-cyhalothrin , Deltamethrin, cypermethrin, bifenthrin, permethrin, permethrin, lavalin, deltamethrin, permethrin, bifenthrin, permethrin, permethrin, Insecticidal, insecticidal double, insecticidal ring, carbendazim, diflubenzuron, flubenzuron, imazapyr, pyriproxyfen or fenzozide.

Further preferably, the active ingredient B is selected from the group consisting of fenpyram, thiamethoxam, clothianidin, imidacloprid, acetamiprid, nitenpyram, diflubenzuron, flufenacil, triflumezopyrimide, and triflumezopyrim , Flupyradifurone, spinosyn, ethyl spinosad, chlorpyrifos, triazophos, chlorfenapyr, fipronil, fipronil, fipronil, deltamethrin, beta-cypermethrin, beta-cyhalothrin, Bifenthrin, fenvalerate, fenvalerate, tefluthrin, beta-cypermethrin, avermectin, methylaminoavermectin benzoate, pymetrozine, ethiprole, flubendicarb Urea, lufenuron, fluazinam, diflubenzuron, butyl ether urea, flubenzuron, chlorfenuron, methoxyfenozide, fenzozide, furan hydrazide, nitraclopyr, acetazolazole , Fenflufen, bifenazate, pyridaben, triazotin, phentermin, bismuth, indoxacarb, fenflufen, chlorantraniliprole, flubendiamide, bromocyanide Amide, Cyclopramid, Tetrachloropyramid, Insecticidal Mono, Insecticidal Double, Fenitrothion, Bacillus thuringiensis, Bacillus sphaericus, Acetylmite, Isocycloseram, Tyclo pyrazoflor, flupyrimin, oxazosulfyl, benzpyrimoxan, fluazaindolizine, fluxametamide, dicloromezotiaz, tioxazafen, fluensulfone, fluhexafon, pyrifluquinazon, prothioconazole, anisole, mesotriazole, flucyclazole, tebuconazole, hexazol, jinggangmycin, spring ray Mycin, tricyclazole, azoxystrobin, azoxystrobin, picoxystrobin, pyraclostrobin, prochloraz, flupronil, veracol, metalaxyl, metalaxyl, biphenylpyridine Any one or a combination of at least two of fenoxystrobin, fluoxastrobin, or fluoxamide.

Further preferably, the active ingredient B is selected from the group consisting of fenpyram, thiamethoxam, imidacloprid, acetamiprid, nitenpyram, fenflufenacil, flufenacil, triflumezopyrim, flupyradifurone, and more Bactericidin, ethyl spinosad, chlorpyrifos, pyracronil, fipronil, deltamethrin, beta-cyhalothrin, bifenthrin, fenvalerate, fenvalerate, tefluthrin , Beta-cyhalothrin, avermectin, avermectin benzoate, pymetrozine, ethiprole, flubendicarb, flubenzuron, fluazinam, butyl ether urea, flubenzuron, alpha Oxfenazide, Nitrofen, Acetofen, Tebufenpyr, Bifenazate, Pyridoxam, Triazotin, Phentermin, Dimethoam, Indoxacarb, Cyflufenazone, Chlorantraniliprole, flubendiamide, bromocrifamide, tetrachloropyramid, insecticidal single, insecticidal double, fenitrothion, Bacillus thuringiensis, acetylfenite, isocycloseram, tyclopyrazoflor, flupyrimin, oxazosulfyl, benzpyrimoxan, fluazaindolizine, fluxametamide, dicloromezotiaz, tioxazafen, fluensulfone, pyrifluquinazon, propylsulfur Myclobutanil, fenpropiconazole, fluconazole, tebuconazole, hexaconazole, Jinggangmycin, tricyclazole, azoxystrobin, oxystrobin, picoxystrobin, pyraclostrobin, biphenyl Any one or a combination of at least two of pyraclostrobin, fluopyramide, prochloraz, flupronil, metalaxyl, or veracol.

As a preferred technical solution of the present application, the medicinal composition containing the metadiamide compound is a medicinal composition comprising the metadiamide compound (active ingredient A) and the active ingredient B as the active ingredients described in Table 2 below:

Table 2

* The numbers correspond to the numbers of the compounds listed in Table 1 above

Preferably, the weight ratio of the active ingredient A and the active ingredient B described in this application is 200: 1-1: 200, for example, 200: 1, 180: 1, 150: 1, 130: 1, 100: 1, 80: 1 , 60: 1, 40: 1, 20: 1, 10: 1, 1: 1, 1:10, 1:30, 1:50, 1:80, 1: 100, 1: 120, 1: 140, 1 : 160, 1: 180 or 1: 200.

In the present application, the pharmaceutical composition containing a metadiamide compound has different preferred weight ratios according to the active ingredient A and active ingredient B contained in it. As a preferred technical solution of the present application, when When the active ingredient A and the active ingredient B of the amide compound pharmaceutical composition are selected from the ingredients shown in Table 3, their preferred weight ratios and particularly preferred weight ratios are shown in Table 3.

table 3

Active ingredient A: Active ingredient B	Preferred weight ratio	Particularly preferred weight ratio
Compound of formula I: Avermectin	100: 1-1: 100	50: 1-1: 10
Compound of formula I: lambda-cyhalothrin	100: 1-1: 100	60: 1-1: 5
Compound of formula I: ethyl spinosad	100: 1-1: 100	20: 1-1: 20
Compound of formula I: Deltamethrin	50: 1-1: 50	10: 1-1: 10
Compound of Formula I: Fenpropathrin	50: 1-1: 50	10: 1-1: 10
Compound of Formula I: Methylavermectin Benzoate	100: 1-1: 100	20: 1-1: 20
Compound of formula I: flubendicarb	50: 1-1: 50	20: 1-1: 20
Compound of formula I: flubenzuron	50: 1-1: 50	20: 1-1: 20
Compound of Formula I: Pyridaben	50: 1-1: 50	10: 1-1: 10
Compound of formula I: chlorantraniliprole	100: 1-1: 100	20: 1-1: 20
Compound of formula I: Thiamethoxam	60: 1-1: 50	20: 1-1: 30
Compound of formula I: clothianidin	60: 1-1: 60	40: 1-1: 40
Compound of formula I	50: 1-1: 50	10: 1-1: 30
Compound of formula I: Nitenpyram	50: 1-1: 50	20: 1-1: 20
Compound of formula I: pymetrozine	100: 1-1: 100	30: 1-1: 30
Compound of formula I: chlorpyrifos	50: 1-1: 50	20: 1-1: 30
Compound of formula I: flubendiamide	100: 1-1: 100	20: 1-1: 20
Compound of formula I: tefluthrin	50: 1-1: 50	20: 1-1: 20
Compound of formula I: lufenuron	50: 1-1: 50	20: 1-1: 20
Compound of formula I: methoxyfenozide	50: 1-1: 50	20: 1-1: 20
Compound of formula I: Diformamidine	50: 1-1: 50	20: 1-1: 20
Compound of formula I: acetamiprid	60: 1-1: 50	10: 1-1: 30
Compound of Formula I: Spinosad	100: 1-1: 100	20: 1-1: 30
Compound of formula I: ethiprole	50: 1-1: 50	20: 1-1: 20
Compound of formula I: flufenacil	50: 1-1: 50	20: 1-1: 20
Compound of formula I: pyracronil	50: 1-1: 50	20: 1-1: 20

Compound of formula I: bifenthrin	50: 1-1: 50	20: 1-1: 20
Compound of formula I: fenflufena	50: 1-1: 50	20: 1-1: 20
Compound of formula I: fluazimid	100: 1-1: 100	20: 1-1: 20
Compound of formula I: fluazinam	50: 1-1: 50	20: 1-1: 20
Compound of formula I: Biphenylhydrazide	50: 1-1: 50	20: 1-1: 20
Compound of formula I: Indoxacarb	50: 1-1: 50	20: 1-1: 20
Compound of formula I: Cypermethram	50: 1-1: 50	20: 1-1: 20
Compound of formula I: acetazolonitrile	50: 1-1: 50	20: 1-1: 20
Compound of formula I: Cyflufenazone	50: 1-1: 50	20: 1-1: 20
Compound of formula I: Tetrachloropyramid	100: 1-1: 100	20: 1-1: 20
Compound of formula I: Fenvalerate	50: 1-1: 50	20: 1-1: 20
Compound of formula I: Butylurea	50: 1-1: 50	20: 1-1: 20
Compound of Formula I: (Fipronil + Flupronil)	50: 1-1: 50	20: 1-1: 20
Compound of formula I: (tebuconazole + oxystrobin)	50: 1-1: 50	20: 1-1: 20
Compound of formula I: (Difenoconazole + veracol)	50: 1-1: 50	20: 1-1: 20

In the present application, the m-diamide compound may also be replaced with a tautomer, an enantiomer, a diastereomer or a salt thereof.

In the present application, a pharmaceutical composition containing the tautomer, enantiomer, diastereomer, or a salt of the m-diamide compound can also exert the same properties as the m-diamide-containing compound described in the present application. The pharmaceutical composition has the same action effect, good insecticidal effect and fast-acting effect at a low dose.

On the other hand, the present application provides the application of the pharmaceutical composition containing an m-bisamide compound as described above for controlling plant diseases or insect pests in agriculture, forestry, and horticulture.

The pharmaceutical composition containing an amide compound of the present application is suitable for controlling various agricultural and forestry, horticultural pests, and health pests and diseases that harm rice, corn, wheat, potatoes, fruit trees, vegetables, other crops, and flowers.

In this application, the pests include lepidoptera, coleoptera, hemiptera, tarptera, diptera, orthoptera, homoptera, isoptera, hymenoptera, and spider mite pests.

Preferably, the pests include but are not limited to: cotton bollworm, diamondback moth, Spodoptera exigua, Spodoptera litura, Pieris rapae, diploid pupae, pupae trichoderma, big pupae, Spodoptera frugipera, rice leaf roller, rice Thrips, western flower thrips, melon thrips, onion thrips, ginger thrips, mango thrips, peach aphid, cotton aphid, alfalfa aphid, apple yellow aphid, wheat aphid, jumping beetle, stink bug, gray planthopper, Brown planthopper, white-backed planthopper, termite, mosquito fly, spider mite, citrus red spider.

The composition of the present application has a wide range of applications, and the scope of plants or crops to be applied mainly includes the following categories: vegetables, cucumbers, loofahs, watermelons, melon, pumpkins, hanging melon, spinach, celery, cabbage, cabbage, gourd, pepper, eggplant , Tomato, shallot, ginger, garlic, leek, strawberry, lettuce, kidney bean, cowpea, broad bean, radish, carrot, potato, yam; cereal, wheat, barley, corn, rice, sorghum; fruit tree, apple, pear, banana , Citrus, grape, lychee, mango; flowers, peony, rose, flamingo; oil crops, peanuts, soybeans, rape, sunflower, sesame; sugar crops, sugar beets, sugar cane; other crops, such as potatoes, sweet potatoes, tobacco and Tea; horticulture, forestry, home health, public health areas, etc .; the above-listed plants or crops have no limiting effect on the scope of use of pesticide compositions.

In another aspect, the present application provides the use of a pharmaceutical composition containing an m-bisamide compound as described above in seed treatment of plants, crops, or flowers.

In another aspect, the present application provides a pharmaceutical formulation comprising a pharmaceutical composition containing an m-diamide compound as described above and an agrochemically acceptable adjuvant and / or carrier.

Preferably, in the pharmaceutical preparation, the weight percentage content of the mesodiamide compound-containing pharmaceutical composition is 0.01-99%, such as 0.01%, 0.1%, 1%, 3%, 5%, 8 %, 10%, 15%, 18%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95% or 99%.

Preferably, the agrochemically acceptable adjuvant includes any one or at least one of a dispersant, a wetting agent, an emulsifier, an antifreeze, a thickener, a defoamer, a preservative, a stabilizer, or a colorant. A combination of the two.

Preferably, the dispersant includes lignin sulfonate, alkylphenol polyoxyethylene ether, naphthalenesulfonic acid formaldehyde condensate sodium salt, fatty amine polyoxyethylene ether, fatty acid polyoxyethylene ester, glycerin fatty acid ester polyoxylate Vinyl ether, polycarboxylate, formaldehyde condensate, calcium alkylbenzenesulfonate, alkylphenol polyoxyethylene ether. The wetting agent is selected from the group consisting of sodium lauryl sulfate, alkyl naphthalene sulfonate, pulverized powder BX, polyoxyethylene ether, EO / PO block polyether, fatty alcohol polyoxyethylene ether, and fatty alcohol polyoxylate. Vinyl ether sulfate, sodium alkyl phosphate, alkyl naphthalene sulfonate, alkyl phenol polyoxyvinyl sulfate. The emulsifier is selected from dodecylbenzenesulfonate, alkylnaphthalenesulfonate, alkylsulfonate, alkylphenol polyoxyethylene ether, benzylphenol polyoxyethylene, phenethylphenol polyoxyethylene Ether, fatty amine polyoxyethylene ether. The antifreeze is selected from ethylene glycol, propylene glycol, and glycerol. The thickener is selected from the group consisting of xanthan gum, hydroxymethyl cellulose, hydroxyethyl cellulose, hydroxypropyl starch, methyl cellulose, sodium starch phosphate, magnesium aluminum silicate, and polyvinyl alcohol. The defoamer is selected from the group consisting of silicone oil, silicone compounds, tributyl phosphate, C10-20 saturated fatty acid compounds, and polyether defoamers. The preservative is selected from the group consisting of formaldehyde, phenyl salicylate, butyl parahydroxybenzoate, and potassium sorbate, and the stabilizer is selected from triphenyl phosphite, epichlorohydrin, epoxy soybean oil, and silicic acid. Magnesium aluminum, the colorant is selected from the group consisting of azo pigments, titanium oxide, and iron oxide.

Preferably, the carrier includes a filler and / or a solvent;

Preferably, the agrochemically acceptable carrier includes a solid carrier and / or a liquid carrier.

Preferably, the solid support includes natural or synthetic clays and silicates, such as natural silica and diatomaceous earth; magnesium silicates such as talc; magnesium aluminum silicates such as kaolinite, kaolin, montmorillonite, and mica; White carbon black, calcium carbonate, light calcium carbonate; calcium sulfate; limestone; sodium sulfate; amine salts such as ammonium sulfate and hexamethylene diamine. Liquid carriers include water and organic solvents. Organic solvents include aromatic hydrocarbons such as xylene, benzene, xylene, toluene, etc .; chlorinated hydrocarbons such as chlorobenzene, vinyl chloride, trichloromethane, dichloromethane, etc .; aliphatic hydrocarbons such as petroleum distillates, Cyclohexane, light mineral oil; alcohols such as isopropanol, butanol, ethylene glycol, propylene glycol, glycerol, and cyclohexanol and their ethers and esters; ketones such as acetone, cyclohexanone, and dimethyl Formamide and N-methyl-pyrrolidone.

During the formulation of the pesticide composition (i.e. the pharmaceutical preparation), the active ingredient may be mixed with a liquid carrier and / or a solid carrier, and auxiliary agents such as emulsifiers, dispersants, stabilizers, wetting agents, adhesives Mixtures, defoamers, antioxidants, etc.

Preferably, the dosage form of the pharmaceutical preparation is a solution, a soluble powder, a soluble granule, an emulsifiable concentrate, a wettable powder, an aqueous emulsion, a suspending agent, a dispersible oil suspending agent, a water-dispersible granule, and a microcapsule suspending agent. , Granules, microemulsions, suspension emulsions, microcapsule suspension-suspensions, ultra-low-volume liquids, hot aerosols, film-spreading oils, suspended seed coatings, dry powders for seeds, suspensions for seeds, and seeds for Powder dissolving agent, seed treatment dispersible powder, seed treatment emulsion or seed treatment liquid.

Preferably, the dosage form of the pharmaceutical preparation is a solution, a soluble granule, a suspension, an emulsifiable concentrate, a wettable powder, an aqueous emulsion, a water-dispersible granule, a dispersible oil suspension, a microcapsule suspension, and an ultra-low capacity. Liquid, hot aerosol, suspension seed coating or seed treatment dispersible powder.

In another aspect, the present application provides a method for controlling plant diseases, which method is: applying an effective dose of a pharmaceutical composition containing an m-diamide compound as described above to a plant disease to be controlled or a growth medium thereof. Or a pharmaceutical formulation as described above.

Preferably, the effective dose is 10-1000g per hectare, such as 10g, 20g, 50g, 80g, 100g, 120g, 150g, 180g, 200g, 250g, 300g, 350g, 400g, 450g, 500g, 600g, 700g, 800g 900g or 1000g, preferably 20-500g per hectare.

The composition of the present application may be applied to the disease or its growth medium in the form of a formulation. The compound of the general formula I is dissolved or dispersed in a carrier as an active ingredient or formulated into a formulation for easier dispersion when used as a fungicide. For example: these chemical preparations can be formulated as solution, emulsifiable concentrate, wettable powder, water emulsion, suspension, dispersible oil suspension, water-dispersible granule, seed treatment, microcapsule suspension, granule, microemulsion , Suspension emulsion, suspension-microcapsule suspension and so on.

Compared with the prior art, this application has the following beneficial effects:

Compared with traditional pesticides, the pesticide composition of the present application has the following advantages in use:

(1) The combination of active ingredient A and active ingredient B in this application has a synergistic effect. The amount of the composition used is greatly reduced compared with the single active ingredient insecticide, acaricide or fungicide, and the control effect is significantly improved;

(2) The control spectrum has been expanded, and it can be applied to the control of various pests and diseases in vegetables, fruit trees, flowers, cereals, oil, sugar and other crops and horticulture, forestry and health;

(3) Delay the development of drug resistance, and use two or more compounds with a combination of action mechanisms to effectively prevent or slow down pests' resistance to a class of compounds with a mechanism of action.

detailed description

The technical solutions of the present application are further described below through specific implementations. Those skilled in the art should understand that the embodiments are merely to help understand the application, and should not be considered as a specific limitation to the application.

Synthesis Example

Synthesis Example 1

N- [2,6-dibromo-4- (1,1,1,2,3,3,3-heptafluoroprop-2-yl) phenyl] -3- [N- (cyclopropylmethyl) Synthesis of benzamido] -2-fluorobenzamide (Compound No. 2), the specific synthesis method is as follows:

(1) Synthesis of 2-fluoro- [3- (cyclopropylmethyl) amino] benzoic acid methyl ester

To the reaction flask were added methyl 2-fluoro-3-aminobenzoate (20 g, 118.23 mmol), bromomethylcyclopropane (20.75 g, 153.70 mmol), and N, N-dimethylformamide (200 mL) in that order. After stirring for 16 h under reflux conditions, when TLC monitored that the reaction was no longer in progress, the heating was turned off to end the reaction. After the reaction solution was cooled to room temperature, water (200 mL) was added to the reaction solution, and extracted with ethyl acetate (100 mL). The organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. Purification by column chromatography (eluent was petroleum ether: ethyl acetate = 10: 1) to obtain methyl 2-fluoro- (3- (cyclopropylmethyl) amino) benzoate (13 g, yield, pale yellow liquid) 49.39%).

(2) Synthesis of methyl 2-fluoro-3- (N- (cyclopropylmethyl) benzamide) benzoate

Add benzoic acid (6.67g, 53.78mmol), toluene (50mL), and dichlorosulfoxide (31.99g, 268.9mmol) to the reaction bottle in this order, and react under reflux for 2h. Concentrate the toluene under reduced pressure. The residue was dissolved in tetrahydrofuran (30 mL) until use. Dissolve methyl 2-fluoro-3- (N-cyclopropylmethylamino) benzoate (10.00 g, 44.82 mmol) in tetrahydrofuran (100 mL), add pyridine (4.25 g, 53.78 mmol), and add the solution dropwise. The obtained benzoyl chloride tetrahydrofuran solution was stirred at room temperature for 4 h. When TLC monitored that the reaction was no longer in progress, the reaction was terminated. The reaction solution was dissolved in ethyl acetate (50 mL), and the organic layer was sequentially washed with 2M hydrochloric acid and saturated sodium bicarbonate, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was purified by column chromatography (eluent). The liquid was petroleum ether: ethyl acetate = 8: 1) to obtain 2-fluoro-3- (N- (cyclopropylmethyl) benzamide) benzoic acid methyl ester (13.00 g, yield 88.70%) as a colorless liquid product. ).

(3) Synthesis of 2-fluoro-3- (N- (cyclopropylmethyl) benzamide) benzoic acid

Methyl 2-fluoro-3- (N- (cyclopropylmethyl) benzamide) benzoate (13.00 g, 40.88 mmol) was dissolved in methanol (100 mL), and a 10% aqueous sodium hydroxide solution (6.54 g) was added. , 163.52 mmol, 65.4 mL), after stirring at room temperature for 2 h, the reaction was monitored by TLC for completion. The methanol was concentrated and removed under reduced pressure. The concentrated residue was dissolved in water (100 mL) and extracted with ethyl acetate (50 mL). The organic phase was discarded, and the pH of the aqueous phase was adjusted to 7 with a 2M aqueous hydrochloric acid solution. (100 mL) extraction, the organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, and then concentrated under reduced pressure to obtain a colorless solution product 2-fluoro-3- (N- (cyclopropylmethyl) benzamide) benzene Formic acid (12.00 g, yield 93.82%).

(4) N- [2,6-Dibromo-4- (1,1,1,2,3,3,3-heptafluoroprop-2-yl) phenyl] -3- [N- (cyclopropyl Synthesis of methyl) benzamide] -2-fluorobenzamide

To the reaction flask were added 2-fluoro-3- (N- (cyclopropylmethyl) benzamide) benzoic acid (0.40 g, 1.28 mmol), toluene (6 mL), and dichlorosulfoxide (0.76 g, 6.40 mmol) in this order. ), Stirred for 2 h under reflux, concentrated toluene under reduced pressure, and dissolved the concentrated residue in tetrahydrofuran (3 mL) for use.

2,6-Dibromo-4-heptafluoroisopropylaniline (0.53g, 1.28mmol) was dissolved in tetrahydrofuran (4mL), and lithium diisopropylaminoamide (0.77mL, 1.54mmol) was added dropwise at -70 ° C. After 5 min, a one-step solution of tetrahydrofuran was added dropwise, and the mixture was stirred at -70 ° C for 30 min. The temperature was raised to room temperature and stirred for 30 min. When TLC monitored that the reaction was no longer in progress, the reaction was terminated. Water (20 mL) was added to the reaction solution, and the mixture was extracted with ethyl acetate (20 mL). The organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was purified by column chromatography (eluent was Petroleum ether: ethyl acetate = 5: 1), the target product (0.17 g, yield 18.64%) was obtained as a white solid.

The ¹ H NMR (400 MHz, CDCl ₃ -d) data of Compound 2 is as follows (δ [ppm]): 8.15-7.85 (m, 4H), 7.63-7.49 (m, 1H), 7.48-7.15 (m, 5H), 3.86 (d, J = 65.5 Hz, 2H), 1.15 (s, 1H), 0.50 (s, 2H), 0.20 (d, J = 30.6 Hz, 2H).

Synthesis Example 2

N- [2-Bromo-4- (1,1,1,2,3,3,3-heptafluoroprop-2-yl) -6-trifluoromethoxyphenyl] -3- [N- ( Cyclopropylmethyl) benzamide] Synthesis of 2-fluorobenzamide (Compound No. 5)

To the reaction flask were added 2-fluoro-3- (N- (cyclopropylmethyl) benzamide) benzoic acid (0.50 g, 1.60 mmol), toluene (6 mL), and dichlorosulfoxide (1.07 g, 9.00 mmol) in this order. ), Stirred for 2 h under reflux, concentrated toluene under reduced pressure, and dissolved the concentrated residue in tetrahydrofuran (3 mL) for use.

2-Bromo-4-heptafluoroisopropyl-6-trifluoromethoxyaniline (0.68g, 1.60mmol) was dissolved in tetrahydrofuran (4mL), and 2M lithium diisopropylamide was added dropwise at -70 ° C. Tetrahydrofuran solution (0.96mL, 1.93mmol). After 5min, a one-step tetrahydrofuran solution was added dropwise, and the mixture was stirred at -70 ° C for 30min. The temperature was raised to room temperature and stirred for 30min. When thin layer chromatography (TLC) monitors that the reaction is no longer in progress, the reaction is terminated. Water (20 mL) was added to the reaction solution, and the mixture was extracted with ethyl acetate (20 mL). The organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was purified by column chromatography (eluent was Petroleum ether: ethyl acetate = 5: 1), the target product (0.24 g, yield 20.50%) was obtained as a white solid.

The ¹ H NMR (400 MHz, CDCl ₃ -d) data of Compound 5 is as follows (δ [ppm]): 8.01-7.81 (m, 2H), 7.58–7.51 (m, 3H), 7.35-7.21 (m, 6H), 3.85 (d, J = 64.0 Hz, 2H), 1.20-1.13 (m, 1H), 0.50 (d, J = 7.8 Hz, 2H), 0.20 (d, J = 32.0 Hz, 2H).

Synthesis Example 3

N- [2-Bromo-4- (1,1,1,2,3,3,3-heptafluoroprop-2-yl) -6- (trifluoromethyl) phenyl] -3- [N- Preparation of (cyclobutylmethyl) benzamido] -2-fluorobenzamide (Compound No. 209):

(1) Add 2-fluoro-3- (N- (cyclobutylmethyl) benzamide) benzoic acid (0.40g, 1.22mmol), toluene (6mL), dichlorosulfoxide (0.73g, 6.11) to the reaction bottle in this order mmol), the reaction was stirred under reflux for 2 h, toluene was concentrated under reduced pressure, and the concentrated residue was dissolved in tetrahydrofuran (3 mL) until use.

2-Bromo-6-trifluoromethyl-4-heptafluoroisopropylaniline (0.50 g, 1.22 mmol) was dissolved in tetrahydrofuran (4 mL), and lithium diisopropylaminoamide (0.73 mL) was added dropwise at -70 ° C. , 1.46 mmol), 5 minutes later, a one-step tetrahydrofuran solution was added dropwise, and the mixture was stirred at -70 ° C for 30 minutes. The temperature was raised to room temperature and stirred for 30 minutes. When TLC monitored that the reaction was no longer in progress, the reaction was terminated. Water (20 mL) was added to the reaction solution, and the mixture was extracted with ethyl acetate (20 mL). The organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was purified by column chromatography (eluent was Petroleum ether: ethyl acetate = 5: 1), the target product (0.08 g, yield 9.13%) was obtained as a yellow solid.

The ¹ H NMR (400 MHz, CDCl ₃ -d) data of Compound 209 is as follows (δ [ppm]): 8.15 (s, 1H), 8.05–7.95 (m, 2H), 7.92 (s, 1H), 7.51–7.43 ( m, 1H), 7.29 (s, 3H), 7.20 (s, 2H), 4.03 (d, J = 53.8Hz, 2H), 2.68 (s, 1H), 2.03–1.67 (m, 6H).

Synthesis Example 4

N- [2-Bromo-4- (1,1,1,2,3,3,3-heptafluoroprop-2-yl) -6- (trifluoromethyl) phenyl] -3- [N- (Cyclohexylmethyl) benzamido] -2-fluorobenzamide (Compound No. 257) was prepared as follows:

(1) Add 2-fluoro-3- (N- (cyclohexylmethyl) benzamide) benzoic acid (0.44g, 1.24mmol), toluene (6mL), and dichlorosulfoxide (0.74g) to the reaction bottle in this order. , 6.19 mmol), stirred for 2 h under reflux conditions, concentrated toluene under reduced pressure, and dissolved the concentrated residue in tetrahydrofuran (3 mL) for use.

(2) Dissolve 2-bromo-6-trifluoromethyl-4-heptafluoroisopropylaniline (0.51g, 1.24mmol) in tetrahydrofuran (4mL), and dropwise add lithium diisopropylamide at -70 ° C (0.74 mL, 1.48 mmol). After 5 min, a one-step solution of tetrahydrofuran was added dropwise, and the mixture was stirred at -70 ° C for 30 min. The temperature was raised to room temperature and stirred for 30 min. When TLC monitored that the reaction was no longer in progress, the reaction was terminated. Water (20 mL) was added to the reaction solution, and the mixture was extracted with ethyl acetate (20 mL). The organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was purified by column chromatography (eluent was Petroleum ether: ethyl acetate = 5: 1), the target product (0.086 g, yield 9.32%) was obtained as a yellow solid.

The 1H NMR (400 MHz, CDCl ₃ -d) data of Compound 257 is as follows (δ [ppm]): 8.12 (s, 1H), 7.93 (d, J = 28.8 Hz, 2H), 7.49 (s, 1H), 7.22 ( d, J = 33.5 Hz, 6H), 3.87 (d, J = 6.7 Hz, 1H), 3.74 (s, 1H), 2.90 (s, 1H), 1.80–1.53 (m, 10H).

Synthesis Example 5

N- [2,6-dibromo-4- (1,1,1,2,3,3,3-heptafluoroprop-2-yl)]-3- [N- (cyclopropylmethyl) -4 -Cyanobenzamide] -2-fluorobenzamide (Compound No. 279):

(1) Synthesis of methyl 2-fluoro-3- (N- (cyclopropylmethyl) -4-cyanobenzamide) benzoate

To the reaction flask were added 4-cyanobenzoic acid (0.80 g, 5.38 mmol), toluene (6 mL), dichlorosulfoxide (3.2 g, 26.9 mmol) in this order, and the reaction was stirred under reflux for 2 h, and the toluene was concentrated under reduced pressure. , The concentrated residue was dissolved in tetrahydrofuran (3 mL) for use. Methyl 2-fluoro- (3- (cyclopropylmethyl) amino) benzoate (1.0 g, 4.48 mmol) was dissolved in tetrahydrofuran (6 mL), and triethylamine (0.74 g, 5.38 mmol) was added, and 4 was added dropwise. -A solution of cyanobenzoyl chloride in tetrahydrofuran, stirred at room temperature for 4h. When TLC monitored that the reaction was no longer in progress, the reaction was terminated. Water (20 mL) was added to the reaction solution, and the mixture was extracted with ethyl acetate (20 mL). The organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was purified by column chromatography (eluent was Petroleum ether: ethyl acetate = 3: 1) to obtain 2-fluoro-3- (4-cyano-N- (cyclopropylmethyl) benzamide) benzoic acid methyl ester (1.40 g, yield Rate 88.83%).

(2) Synthesis of 2-fluoro-3- (N- (cyclopropylmethyl) -4-cyanobenzamide) benzoic acid

Dissolve methyl 2-fluoro-3- (N- (cyclopropylmethyl) -4-cyanobenzamide) benzoate (1.40 g, 3.96 mmol) in methanol (20 mL), and add 10% hydrogen Aqueous sodium oxide solution (0.63 g, 15.86 mmol, 6.3 mL) was stirred at room temperature for 2 h. The reaction was monitored by TLC for completion. The methanol was concentrated and removed under reduced pressure. The concentrated residue was dissolved in water (20 mL) and extracted with ethyl acetate (10 mL). The organic phase was discarded, and the pH of the aqueous phase was adjusted to 7 with a 2M aqueous hydrochloric acid solution. (10 mL), the organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure to obtain 2-fluoro-3- (N- (cyclopropylmethyl) -4-cyanobenzamide group ) Benzoic acid (1.30 g, yield 96.79%), white solid.

(3) N- [2,6-Dibromo-4- (1,1,1,2,3,3,3-heptafluoroprop-2-yl)]-3- [N- (cyclopropylmethyl ) -4-cyanobenzamide] Synthesis of 2-fluorobenzamide

To the reaction flask were added 2-fluoro-3- (N- (cyclopropylmethyl) -4-cyano-benzamide) benzoic acid (0.75 g, 2.22 mmol), toluene (6 mL), and dichlorosulfoxide in this order. (1.31 g, 11.10 mmol), stirred for 2 h under reflux, and concentrated toluene under reduced pressure. The concentrated residue was dissolved in tetrahydrofuran (3 mL) until use.

2,6-Dibromo-4-heptafluoroisopropylaniline (0.91g, 2.22mmol) was dissolved in tetrahydrofuran (4mL), and lithium diisopropylaminoamide (1.30mL, 2.66mmol) was added dropwise at -70 ° C. After 5 min, a one-step solution of tetrahydrofuran was added dropwise, and the mixture was stirred at -70 ° C for 30 min. The temperature was raised to room temperature and stirred for 30 min. When TLC monitored that the reaction was no longer in progress, the reaction was terminated. Water (20 mL) was added to the reaction solution, and the mixture was extracted with ethyl acetate (20 mL). The organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was purified by column chromatography (eluent was Petroleum ether: ethyl acetate = 3: 1) to obtain the target product (0.28 g, yield 17.18%).

¹ H NMR (400MHz, Chloroform-d) δ of compound 279 8.07 (s, 1H), 7.97–7.81 (m, 2H), 7.61–7.38 (m, 4H), 7.29 (s, 1H), 7.11 (d , J = 5.3Hz, 1H), 3.89 (s, 1H), 3.82-3.70 (m, 1H), 1.09 (s, 1H), 0.65–0.44 (m, 2H), 0.20 (d, J = 29.6Hz, 2H).

Synthesis Example 6

N- [2-Bromo-4- (1,1,1,2,3,3,3-heptafluoroprop-2-yl) -6- (trifluoromethyl) phenyl] -3- [N- Synthesis of (cyclopropylmethyl) -4-cyanobenzamide] -2-fluorobenzamide (Compound No. 281):

To the reaction flask were added 2-fluoro-3- [N- (cyclopropylmethyl) -4-cyanobenzamide] benzoic acid (0.75 g, 2.22 mmol), toluene (6 mL), and dichlorosulfoxide ( 1.31 g, 11.10 mmol), stirred under reflux for 2 h, and concentrated under reduced pressure. The concentrated residue was dissolved in tetrahydrofuran (3 mL) for use.

2-Bromo-6-trifluoromethyl-4-heptafluoroisopropylaniline (0.90 g, 2.22 mmol) was dissolved in tetrahydrofuran (4 mL), and lithium diisopropylamino (1.30 mL) was added dropwise at -70 ° C. , 2.66 mmol), 5 minutes later, the 2-fluoro-3- [N- (cyclopropylmethyl) -4-cyanobenzamide] benzoyl chloride tetrahydrofuran solution prepared in one step was added dropwise, and the mixture was stirred at -70 ° C. 30min, warm to room temperature and continue stirring for 30min. When TLC monitored that the reaction was no longer in progress, the reaction was terminated. A saturated ammonium chloride aqueous solution (20 mL) was added to the reaction solution, and the mixture was extracted with ethyl acetate (20 mL). The organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was purified by column chromatography ( The eluent was petroleum ether: ethyl acetate = 3: 1), and N- [2-bromo-4- (1,1,1,2,3,3,3-heptafluoroprop-2-yl)- 6- (trifluoromethyl) phenyl] -3- [N- (cyclopropylmethyl) -4-cyanobenzamido] -2-fluorobenzamide (0.24 g, yield 14.91%).

¹ H NMR (400 MHz, CDCl ₃ -d), δ [ppm] of compound 281: 8.14 (d, J = 2.0 Hz, 1 H), 8.12-7.94 (m, 2 H), 7.91 (t, J = 1.4 Hz, 1H), 7.58-7.39 (m, 4H), 7.32 (t, J = 7.9Hz, 1H), 3.81 (dd, J = 76.0, 18.8Hz, 2H), 1.11 (br s, 1H), 0.5 (br s , 2H), 0.20 (d, J = 36.7 Hz, 2H).

Synthesis Example 7

N- [2-Bromo-4- (1,1,1,2,3,3,3-heptafluoroprop-2-yl) -6-trifluoromethoxyphenyl] -3- [N- ( (Cyclopropylmethyl) -4-cyanobenzamide] -2-fluorobenzamide (Compound No. 282)

To the reaction flask were added 2-fluoro-3- (N- (cyclopropylmethyl) -4-cyanobenzamide) benzoic acid (0.51 g, 1.50 mmol), toluene (6 mL), and dichlorosulfoxide ( 1.31 g, 11.10 mmol), stirred for 2 h under reflux, and concentrated toluene under reduced pressure. The concentrated residue was dissolved in tetrahydrofuran (3 mL) for use.

2-Bromo-4-heptafluoroisopropyl-6-trifluoromethoxyaniline (0.64g, 1.50mmol) was dissolved in tetrahydrofuran (4mL), and 2M lithium diisopropylaminoamide was added dropwise at -70 ° C. Tetrahydrofuran solution (0.90mL, 1.80mmol). After 5min, a one-step tetrahydrofuran solution was added dropwise, and the mixture was stirred at -70 ° C for 30min. The temperature was raised to room temperature and stirred for 30min. When TLC monitored that the reaction was no longer in progress, the reaction was terminated. Water (20 mL) was added to the reaction solution, and the mixture was extracted with ethyl acetate (20 mL). The organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was purified by column chromatography (eluent was Petroleum ether: ethyl acetate = 3: 1) to obtain the target product (0.17 g, yield 15.04%).

The ¹ H NMR (400 MHz, DMSO-d6)) data of Compound 282 is as follows (δ [ppm]): 10.55 (s, 1H), 8.11 (d, J = 2.0 Hz, 1H), 7.82-7.35 (m, 4H) , 7.65-7.22 (m, 4H), 3.88-3.60 (m, 2H), 1.09-0.92 (m, 1H), 0.42 (d, J = 8.0Hz, 2H), 0.13 (d, J = 27.9Hz, 2H ).

Synthesis Example 8

N- [2-Bromo-4- (1,1,1,2,3,3,3-heptafluoroprop-2-yl) -6- (trifluoromethyl) phenyl] -3- [N- Preparation of (cyclopropylmethyl) -4- (trifluoromethyl) benzamido] -2-fluorobenzamide (Compound No. 484):

(1) Add 2-fluoro-3- (4-trifluoromethyl-N- (cyclopropylmethyl) benzamide) benzoic acid (0.45g, 1.12mmol) and toluene (6mL) to the reaction bottle in this order. Dichlorosulfoxide (0.67 g, 5.60 mmol) was stirred for 2 h under reflux, and toluene was concentrated under reduced pressure. The concentrated residue was dissolved in tetrahydrofuran (3 mL) for use.

(2) Dissolve 2-bromo-6-trifluoromethyl-4-heptafluoroisopropylaniline (0.46 g, 1.12 mmol) in tetrahydrofuran (4 mL), and dropwise add lithium diisopropylamide at -70 ° C. (0.70 mL, 1.42 mmol). After 5 min, a one-step solution of tetrahydrofuran was added dropwise, and the mixture was stirred at -70 ° C for 30 min. The temperature was raised to room temperature and stirred for 30 min. When TLC monitored that the reaction was no longer in progress, the reaction was terminated. Water (20 mL) was added to the reaction solution, and the mixture was extracted with ethyl acetate (20 mL). The organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was purified by column chromatography (eluent was Petroleum ether: ethyl acetate = 3: 1) to obtain the target product (0.11 g, yield 13.75%).

The ¹ H NMR (400MHz, CDCl ₃ -d) data of compound 484 is as follows (δ [ppm]): 8.21–7.79 (m, 4H), 7.66–7.28 (m, 5H), 3.85 (d, J = 104.7Hz, 2H), 1.12 (s, 1H), 0.51 (s, 2H), 0.20 (d, J = 42.7Hz, 1H).

Synthesis Example 9

N- [2-Bromo-4- (1,1,1,2,3,3,3-heptafluoroprop-2-yl) -6- (trifluoromethyl) phenyl] -3- [N- (Cyclopropylmethyl) -4-chlorobenzamido] -2-fluorobenzamide (Compound No. 526) was prepared as follows:

(1) Add 2-fluoro-3- (4-chloro-N- (cyclopropylmethyl) benzamide) benzoic acid (0.60g, 1.76mmol), toluene (6mL), and dichloromethane to the reaction bottle in this order. Sulfone (1.04 g, 8.80 mmol) was stirred under reflux for 2 h, and toluene was concentrated under reduced pressure. The concentrated residue was dissolved in tetrahydrofuran (3 mL) for use.

(2) Dissolve 2-bromo-6-trifluoromethyl-4-heptafluoroisopropylaniline (0.72 g, 1.76 mmol) in tetrahydrofuran (4 mL), and dropwise add lithium diisopropylamide at -70 ° C. (1.05 mL, 2.11 mmol). After 5 min, a one-step solution of tetrahydrofuran was added dropwise, and the mixture was stirred at -70 ° C for 30 min. The temperature was raised to room temperature and stirred for 30 min. When TLC monitored that the reaction was no longer in progress, the reaction was terminated. Water (20 mL) was added to the reaction solution, and the mixture was extracted with ethyl acetate (20 mL). The organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was purified by column chromatography (eluent was Petroleum ether: ethyl acetate = 3: 1) to obtain the target product (0.15 g, yield 11.63%).

The ¹ H NMR (400MHz, CDCl ₃ -d) data of compound 526 is as follows (δ [ppm]): 8.18–7.84 (m, 4H), 7.53 (t, J = 7.7Hz, 1H), 7.37–7.07 (m, 4H), 3.81 (d, J = 85.0 Hz, 2H), 1.11 (s, 1H), 0.49 (s, 2H), 0.17 (d, J = 32.1 Hz, 2H).

Synthesis Example 10

N- [2-Bromo-4- (1,1,1,2,3,3,3-heptafluoroprop-2-yl) -6- (trifluoromethyl) phenyl] -3- [N- (Cyclopropylmethyl) -4-fluorobenzamide] -2-fluorobenzamide (Compound No. 620) was prepared as follows:

To the reaction flask were added 2-fluoro-3- [N- (cyclopropylmethyl) -4-fluoro-benzamide] benzoic acid (2.20 g, 6.67 mmol), toluene (20 mL), and dichlorosulfoxide ( 3.97 g, 33.35 mmol), stirred under reflux for 2 h, and concentrated under reduced pressure to obtain 2-fluoro-3- [N- (cyclopropylmethyl) -4-fluorobenzamide] benzoyl chloride. 2-Bromo-6-trifluoromethyl-4-heptafluoroisopropylaniline (3.26g, 7.99mmol), N, N diisopropylethylamine (1.72g, 13.30mmol), 4-N, N -Dimethylaminopyridine (0.33g, 2.69mmol) was added to 2-fluoro-3- [N- (cyclopropylmethyl) -4-fluorobenzamide] benzoyl chloride, and stirred at 120 ° C for reaction After 2h, the heating was stopped. Water (20 mL) was added to the reaction solution, and the mixture was extracted with ethyl acetate (20 mL). The organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was purified by column chromatography (eluent was PE: EA = 3: 1) to obtain the target product (1.80 g, yield 37.5%).

¹ H NMR (400 MHz, DMSO-d ₆ ) δ [ppm] of compound 620: 10.56 (s, 1H), 8.41 (s, 1H), 7.95 (s, 1H), 7.70-7.56 (m, 2H), 7.38 -7.32 (m, 3H), 7.09 (br s, 2H), 3.69 (br s, 2H), 1.03-1.01 (m, 1H), 0.41-0.39 (m, 2H), 0.08-0.06 (m, 2H) .

Synthesis Example 11

N- [2-Bromo-4- (1,1,1,3,3,3-hexafluoroprop-2-yl) -6-trifluoromethylphenyl] -3- [N- (cyclopropylmethyl Preparation of 4-fluorobenzamide] -2-fluorobenzamide (Compound No. 75)

(1) N- [2-Bromo-4- (1,1,1,2,3,3,3-heptafluoroprop-2-yl) -6-trifluoromethylphenyl] -2-fluoro- Synthesis of 3-nitrobenzamide

To the reaction flask were added 2-fluoro-3-nitrobenzoic acid (2.28g, 12.32mmol), toluene (20mL), dichlorosulfoxide (7.33g, 61.59mmol) in this order, and the reaction was stirred under reflux for 2h. It was concentrated under reduced pressure to obtain 2-fluoro-3-nitrobenzoyl chloride. 2-Bromo-4- (1,1,1,2,3,3,3-heptafluoroprop-2-yl) -6-trifluoromethylaniline (4.56 g, 11.18 mmol), N, N- Diisopropylethylamine (4.11g, 3.18mmol) and 4-N, N-dimethylpyridine (0.28g, 2.24mmol) were added to 2-fluoro-3-nitrobenzoyl chloride chloride, and the temperature was raised to 110 The reaction was carried out at a temperature of 8 ° C. After 8 hours, the reaction solution was cooled to room temperature, and 100 mL of ethyl acetate and 100 mL of water were added. The layers were separated and extracted. The organic layer was taken out. The residue was purified by column chromatography (eluent was petroleum ether: ethyl acetate = 94: 6) to obtain the target product (3.8 g, yield 59.2%).

(2) 3-nitro-N- [2-bromo-4- (1,1,1,3,3,3-hexafluoroprop-2-yl) -6-trifluoromethylphenyl] -2 -Fluorobenzamide synthesis

N- [2-Bromo-4- (1,1,1,2,3,3,3-heptafluoroprop-2-yl) -6-trifluoromethylphenyl] -2-fluoro-3- Nitrobenzamide (1.28 g, 2.0 mmol) was dissolved in dimethyl sulfoxide (15 mL), sodium borohydride (155 mg, 4.0 mmol) was added in portions, and the temperature was raised to 60 ° C for 4.0 h. The reaction solution was cooled to room temperature, and 50 mL of water was added to the reaction solution. The mixture was extracted with 50 mL of ethyl acetate, and the organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was purified by column chromatography. (The eluent was petroleum ether: ethyl acetate = 85: 15), 0.8 g of a yellow oil was obtained, and the yield was 71%.

(3) 3-amino-N- [2-bromo-4- (1,1,1,3,3,3-hexafluoroprop-2-yl) -6-trifluoromethylphenyl] -2- Synthesis of flubenzamide

N- [2-Bromo-4- (1,1,1,3,3,3-hexafluoroprop-2-yl) -6-trifluoromethylphenyl] -2-fluoro-3-nitro Benzoamide (773 mg, 1.39 mmol) was dissolved in ethanol (20 mL), concentrated hydrochloric acid (0.2 mL) and stannous chloride dihydrate (1.25 g, 5.56 mmol) were added in that order, and refluxing was added for 3 h. The reaction solution was evaporated to dryness under reduced pressure, and the Ph value of the solution was adjusted to 12 with a 10% sodium hydroxide aqueous solution, and extracted with ethyl acetate (50 mL). The organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, and then decompressed. It was concentrated under reduced pressure, and the residue was purified by column chromatography (eluent was petroleum ether: ethyl acetate = 5: 1) to obtain 669 mg of a yellow solid with a yield of 91.27%.

(4) N- [2-Bromo-4- (1,1,1,3,3,3-hexafluoroprop-2-yl) -6-trifluoromethylphenyl] -3- (cyclopropylmethyl) Of phenylamino) -2-fluorobenzamide

3-amino-N- [2-bromo-4- (1,1,1,3,3,3-hexafluoroprop-2-yl) -6-trifluoromethylphenyl] -2-fluorobenzene Formamide (669 mg, 1.27 mmol) was dissolved in 1,2-dichloroethane (20 mL), cyclopropanal (83 mg, 1.14 mmol), and trifluoroacetic acid (870 mg, 7.62 mmol) were added in that order, and the mixture was stirred at room temperature for 10 minutes. Sodium triacetoxyborohydride (810 mg, 3.81 mmol) was added in portions. When the thin layer chromatography showed that the reaction was no longer in progress, the reaction was terminated. A saturated sodium bicarbonate aqueous solution was added to the reaction solution, the pH was adjusted to 8, and the mixture was extracted with dichloromethane (20 mL). The organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was passed through a column. Purification by chromatography (eluent was petroleum ether: ethyl acetate = 10: 1) to obtain a pale yellow solid (387 mg, yield 52.58%).

(5) N- [2-Bromo-4- (1,1,1,3,3,3-hexafluoroprop-2-yl) -6-trifluoromethylphenyl] -3- [N- ( Cyclopropylmethyl) -4-fluorobenzamide] -2-fluorobenzamide

In N- [2-bromo-4- (1,1,1,3,3,3-hexafluoroprop-2-yl) -6-trifluoromethylphenyl] -3- (cyclopropylmethylamino ) -2-Fluorobenzoamide (0.38 g, 0.65 mmol) in a solution of tetrahydrofuran (5 mL), pyridine (210 mg, 2.6 mmol), and p-fluorobenzoyl chloride (120 mg, 0.78 mmol) were sequentially added, and the mixture was reacted at reflux for 2.5 hours. The reaction solution was cooled to room temperature, and 20 mL of water was added. The organic layer was taken with 20 mL of ethyl acetate. The organic layer was washed with 5% dilute hydrochloric acid, saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was subjected to column chromatography. Purification (eluent was petroleum ether: ethyl acetate = 6: 1) to obtain a white solid (372 mg, yield 81.40%).

The ¹ H NMR (400 MHz, DMSO-d6) data of Compound 75 is as follows (δ [ppm]): 10.57 (s, 1H), 8.43 (d, J = 2.0 Hz, 1 H), 7.97 (d, J = 2.0 Hz, 1H), 7.81-7.47 (m, 2H), 7.60-7.51 (m, 2H), 7.22-7.16 (m, 1H), 7.10 (br s, 2H), 3.77 (d, J = 6.8Hz, 2H), 1.08-0.99 (m, 1H), 0.46-0.41 (m, 2H), 0.15-0.12 (m, 2H).

Synthesis Example 12

N- [2-Bromo-4- (1,1,1,2,3,3,3-heptafluoroprop-2-yl) -6- (trifluoromethyl) phenyl] -3- [N- (1-Cyclopropyl-ethyl) -benzamido] -2-fluorobenzamide (Compound No. 45) was prepared as follows:

(1) Synthesis of methyl 3- [N- (1-cyclopropylethyl) amino] -2-fluorobenzoate

Methyl 2-fluoro-3-aminobenzoate (2.00 g, 11.82 mmol) was dissolved in 1,2-dichloroethane (65 mL), and cyclopropylmethyl ketone (2.98 g, 35.47 mmol) was sequentially added at room temperature. ), Trifluoroacetic acid (8.08 g, 70.92 mmol) and sodium triacetylborohydride (7.51 g, 35.47 mmol), the reaction was heated to 45 ° C. for 1 h. When TLC monitored that the reaction was no longer in progress, the reaction was terminated. A saturated NaHCO ₃ solution (50 mL) was added to the reaction solution, and extracted with dichloromethane (80 mL). The organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was purified by column chromatography (leaching). The washing solution was petroleum ether: ethyl acetate = 10: 1) to obtain the target product (1.50 g, yield 53.5%) as a colorless oil.

(2) Synthesis of 3- [N- (1-cyclopropyl-ethyl) benzamido] -2-fluorobenzoate

Add benzoic acid (1.54 g, 12.64 mmol), toluene (15 mL), and dichlorosulfoxide (6.27 g, 52.68 mmol) to the reaction bottle in this order, and stir the reaction under reflux for 2 h. Concentrate the toluene under reduced pressure. The residue was dissolved in tetrahydrofuran (5 mL) until use.

Methyl 3- [N- (1-cyclopropylethyl) amino] -2-fluorobenzoate (2.50 g, 10.54 mmol) was dissolved in tetrahydrofuran (15 mL), and triethylamine (1.60 g, 15.80 mmol) was added sequentially. ) And the tetrahydrofuran solution of the acid chloride prepared in the previous step, and stirred at 80 ° C. for 6 h. When TLC monitored that the reaction was no longer in progress, the reaction was terminated. Water (50 mL) was added to the reaction solution, and the mixture was extracted with ethyl acetate (60 mL). The organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was purified by column chromatography (eluent was Petroleum ether: ethyl acetate = 10: 1), the target product (1.03 g, yield 28.6%) was obtained as a yellow solid.

(3) 3- [N- (1-Cyclopropyl) -ethyl) benzamido] -2-fluorobenzoic acid

Methyl 3-[(1-cyclopropyl-ethyl) benzamido] -2-fluorobenzoate (1.00 g, 2.93 mmol) was dissolved in methanol (10 mL), and a 10% aqueous sodium hydroxide solution was added. (0.46 g, 11.72 mmol, 4.6 mL) and stirred at room temperature for 2 h. The reaction was monitored by TLC for completion. The methanol was concentrated and removed under reduced pressure. The concentrated residue was dissolved in water (20 mL) and extracted with ethyl acetate (10 mL). The organic phase was discarded, and the pH of the aqueous phase was adjusted to 3 with a 2M aqueous hydrochloric acid solution. (10 mL) was extracted, and the organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, and then concentrated under reduced pressure to obtain the target product (0.60 g, yield 62.6%).

(4) N- (2-bromo-4- (1,1,1,2,3,3,3-heptafluoroprop-2-yl) -6- (trifluoromethyl) phenyl) -3- Synthesis of (N- (1-cyclopropyl-ethyl) benzamide) -2-fluorobenzamide

To the reaction flask were added 3- (N- (1-cyclopropyl) -ethyl) benzamido) -2-fluorobenzoic acid (0.60 g, 1.83 mmol), toluene (6 mL), and dichlorosulfoxide ( 1.09 g, 9.16 mmol), stirred at 140 ° C. for 2 h, and concentrated toluene under reduced pressure. The concentrated residue was dissolved in tetrahydrofuran (2 mL) for use.

2-Bromo-6-trifluoromethyl-4-heptafluoroisopropylaniline (0.75 g, 1.83 mmol) was dissolved in tetrahydrofuran (6 mL), and lithium diisopropylaminoamide (1.10 mL) was added dropwise at -70 ° C. , 2.20 mmol). After 5 min, a one-step solution of tetrahydrofuran was added dropwise, and the mixture was stirred at -70 ° C for 30 min. The temperature was raised to room temperature and continued to be stirred for 30 min. When TLC monitored that the reaction was no longer in progress, the reaction was terminated. Water (20 mL) was added to the reaction solution, and the mixture was extracted with ethyl acetate (20 mL). The organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was purified by column chromatography (eluent was Petroleum ether: ethyl acetate = 5: 1), the target product (0.23 g, yield 17.5%) was obtained as a yellow solid.

The ¹ H NMR (400 MHz, CDCl ₃ -d) data of Compound 45 is as follows (δ [ppm]): 8.19 (s, 1H), 8.05–7.95 (m, 1H), 7.89 (s, 1H), 7.77–7.73 ( m, 1H), 7.56--7.52 (m, 1H), 7.28--7.11 (m, 6H), 4.26--4.23 (m, 1H), 1.63 (s, 2H), 1.51 (s, 1H), 0.89--0.40 ( m, 5H).

In addition to the compounds described above, some of the compounds in Table 1 are prepared or can be prepared by a similar method as in Synthesis Examples 1-12, and the NMR data of some of the compounds synthesized with reference to Synthesis Examples 1-12 are given in Table 4 below.

Table 4

Synthesis Example 13

N- [2-Bromo-4- (1,1,1,2,3,3,3-heptafluoroprop-2-yl) -6- (trifluoromethyl) phenyl] -3- [N- Preparation of (cyclopropylmethyl) -4- (5-trifluoromethyl-1,2,4-oxadiazol-3-yl) benzamido] -2-fluorobenzamide (Compound No. 602) :

(1) Add N- (2-bromo-4- (heptafluoroisopropan-2-yl) -6-trifluoromethylphenyl) -3- (N- (cyclopropylmethyl) to the reaction bottle in order. 4- (N`-hydroxycarbamoyl) benzamide) -2-fluorobenzamide (0.06 g, 0.08 mmol), dichloromethane (3 mL), trifluoroacetic anhydride (0.08 g, 0.40 mmol), The reaction was refluxed at 45 ° C for 2h. When TLC monitored that the reaction was no longer in progress, the reaction was terminated. Water (30 mL) was added to the reaction solution, and the mixture was extracted with dichloromethane (30 mL). The organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was purified by column chromatography (eluent was Petroleum ether: ethyl acetate = 3: 1) to obtain the target product (0.025 g, yield 37.80%) as a white solid.

ESI-MS of compound 602: m / z = 840.0 [M + H].

Other compounds of the general formula I of the present application can be synthesized with reference to the methods described above.

Formulation examples

The following examples are used to illustrate the composition ratio and preparation method of the present application:

Formulation example 1, 20% compound 9 · furanid solution (the concentration refers to the sum of the concentrations of compound 9 and furanid in its solution)

Table 5 20% Compound 9 · furacloprid solution

name	Hundred percent (W / W,%)	Note
Compound 9	10	Active ingredient A
Dinotefuran	10	Active ingredient B
Propylene glycol methyl ether	12	Cosolvent
Fatty alcohol polyoxyethylene ether (AEO-9)	5	moisturizer
Deionized water	Make up 100	Solvent

Preparation method: Calculate the amount of each material according to the formula. In a 250ml three-necked flask, add deionized water, add propylene glycol methyl ether, then add compound 9, furfuran, heat to 30-40 ° C and stir for 2 hours. Finally add AEO -9 is uniformly dissolved, and filtered to obtain a solution containing 18% of compound 309 · furacloprid.

Formulation Example 2, 35% Compound 13 · Chlorpyrifos EC

Table 6 35% Compound 13 · Chlorpyrifos EC

name	Hundred percent (W / W,%)	Note
Compound 13	5	Active ingredient A
Chlorpyrifos	30	Active ingredient B
Calcium dodecylbenzenesulfonate	5	Emulsifier
Castor oil polyoxyethylene ether	5	Emulsifier
Xylene	Make up 100	Solvent

Preparation method: Calculate the amount of each material according to the formula. In a 250mL three-necked flask, add xylene, add compound 13, chlorpyrifos, calcium dodecylbenzenesulfonate, and castor oil polyoxyethylene ether, and stir at 40-50 ° C After 1.5 hours, filtering, 45% compound 4 · chlorpyrifos EC was obtained.

Formulation Example 3, 30% Compound 616 · Avermectin Wettable Powder

Table 7 30% Compound 616 · Avermectin Wettable Powder

name	Hundred percent (W / W,%)	Note
Compound 616	25	Active ingredient A
Avermectin	5	Active ingredient B
Sodium dodecyl sulfate	1.5	moisturizer
Sodium lignosulfonate	6	Dispersant
Kaolin	Make up 100	Carrier

Preparation method: Calculate the amount of each material according to the formula. After compound 616, avermectin, sodium lauryl sulfate, sodium lignin sulfonate, and kaolin are mixed evenly, use an air jet mill to pulverize to an average particle size of 10 microns. That is, 30% of compound 616 · avermectin wettable powder was obtained.

Formulation Example 4, 15% Compound 627 · Methamidophosphine Water Emulsion

Table 8 15% Compound 627 · Methamidophosphine Water Emulsion

Preparation method: Calculate the amount of each material according to the formula, dissolve compound 627, acephate, castor oil polyoxyethylene ether, and xylene uniformly at 40-50 ° C as phase A; deionized water, propylene glycol, and three Styrylphenol polyoxyethylene ether phosphate is stirred and dissolved uniformly as phase B; under high shear, phase A is slowly added to phase B, sheared to an average particle diameter of 1.5 microns, and 0.1 part of carson 10 parts 1% The xanthan gum solution was stirred for 30 minutes to obtain a 15% compound 627 · acephate aqueous emulsion.

Formulation Example 5, 38% Compound 628 · ethaconazole suspension

Table 9 38% Compound 628 · Ebendazole Suspension

Preparation method: Calculate the amount of each material according to the formula, stir and dissolve the deionized water, propylene glycol, tristyryl phenol polyoxyethylene ether phosphate, sodium lignin sulfonate, carson, and defoamer, and add acetazole Shear with compound 628 uniformly, and then grind it to an average particle size of 2 micrometers with a sand mill. Add 10 parts of a 1% xanthan gum solution and stir for 30 minutes to obtain 38% compound 628 · ethaconazole suspension.

Formulation Example 6, 25% Compound 632 · Chlorantraniliprole Water Dispersible Granules

Table 10 25% Compound 632 · Chlorantraniliprole Water Dispersible Granules

name

Hundred percent (W / W,%)

Note

Compound 632	15	Active ingredient A
Chlorantraniliprole	10	Active ingredient B
Sodium dodecyl sulfate	1.5	moisturizer
Sodium lignosulfonate	6	Dispersant
Naphthalene formaldehyde polymer sodium sulfonate	2	Dispersant
Ammonium sulfate	5	Disintegrant
corn starch	20	filler
Kaolin	Make up 100	filler

Preparation method: Calculate the amount of each material according to the formula, and mix compound 632, chlorantraniliprole, sodium lauryl sulfate, sodium lignin sulfonate, sodium naphthalene formaldehyde polymer sulfonate, ammonium sulfate, corn starch, and kaolin Homogeneous, pulverized to an average particle size of 10-15 microns by a jet mill, kneaded with 17% of the powder, and then granulated by rotary extrusion, dried at 50 ° C for 3 hours, and sieved to obtain 25% of the compound 632. Chlorantraniliprole water dispersible granules.

Formulation Example 7, 15% Compound 636 · methylaminoavermectin benzoate dispersible oil suspension

Table 11 15% Compound 636 · methylamino Avermectin benzoate dispersible oil suspension

name	Hundred percent (W / W,%)	Note
Compound 636	10	Active ingredient A
Methylavermectin benzoate	5	Active ingredient B
Fatty acid polyoxyethylene ether	12	Emulsifier
Styrylphenol polyoxyethylene ether	4	Emulsifier
Organic bentonite	1	Thickener
Fumed silica	1	stabilizer
Methyl oleate	Make up 100	Carrier

Preparation method: Calculate the amount of each material according to the formula, stir and dissolve methyl oleate, fatty acid polyoxyethylene ether, and styrylphenol polyoxyethylene ether, and add compound 636, methylamino avermectin benzoate, The organic bentonite and fumed silica were uniformly sheared, and then ground to an average particle diameter of 4 microns by a sand mill to obtain 15% of a compound 636 · methylaminoavermectin benzoate dispersible oil suspension agent.

Formulation Example 8, 40% Compound 644 · Froxacin · thiamethoxam Suspension Seed Coating

Table 12 40% Compounds

Preparation method: Calculate the amount of each material according to the formula. Dissolve the deionized water, urea, defoaming agent, dye, 1799, tristyryl phenol polyoxyethylene ether phosphate, fatty alcohol polyoxyethylene ether, and cardon to dissolve them uniformly. Add compound 644, fluprothalin, and thiamethoxam to shear uniformly, and then grind it to an average particle size of 2 microns with a sand mill. Add 10 parts of 1% xanthan gum solution and stir for 30 minutes to obtain 40% compound 644 ·. Bacteriochloride · thiamethoxam suspension seed coating agent.

Formulation Example 9, 20% Compound 627 · Indoxacarb Microcapsule Suspension

Table 13 20% Compound 627 · Indoxacarb Microcapsule Suspension

Preparation method: Calculate the amount of each material according to the formula. Dissolve compound 627, indoxacarb, polyaryl polymethylene polyisocyanate, and xylene uniformly at 40-50 degrees as Phase A; take deionized water, D-800, propylene glycol, uniformly dissolve, as phase B; under high shear, slowly add phase A to phase B, cut to an average particle size of 2 to 3 microns, then add the material to a three-necked flask, add hexane Amine was stirred and reacted at 50-60 ° C for 10 hours, and tristyrylphenol polyoxyethylene ether phosphate, carson, 1522, and 1% xanthan gum solution were added and stirred for 1 hour to obtain 20% compound 627. Indoxacarb Microencapsulated suspension.

Biometric Example

Bioassay Example 1

In this embodiment, the insecticidal activity of the prepared m-bisamide compound on pupae diploid is determined by the following method:

Cultivate rice in a plastic pot with a diameter of 9cm and a height of 10cm in the greenhouse. When the rice grows to a plant height of about 25cm, choose a robust and consistent growing rice seedling, cut the ground part, remove the leaves, and retain the rice stalk, about 8cm Long, spare. The rice stem immersion method is used to pour the medicine solution into a petri dish (the amount of the medicine solution is about 40 mL), and the rice stem is immersed in the medicine solution. After soaking for 10s, take it out and place it in a cool place to dry. Put a moisturizing cotton ball at the bottom of the glass finger tube, put 5 treated rice stalks into each tube, and receive 10 third-instar larvae of larvae, repeat each treatment 3 times, seal the tube with a cotton black cloth, and tighten the rubber band. Place in a light incubator at 28 ° C in the dark. The number of live worms was investigated 3 days after the treatment, and the total number of insects was also investigated 3 days after the treatment. The mortality of each treatment was calculated.

The test results are as follows:

The following compounds have a good insecticidal effect and preventive effect (that is, the mortality rate leading to the death of pests at the test concentration of the compound) ≥90% 3 days after the concentration of the compound is 50 ppm: Compounds 7, 9, 12, 279, 527, 536 , 558, 607, 625, 626, 637, 638, 640, 642, 645, 646.

The following compounds have a good insecticidal effect at a concentration of 10 ppm, and 3 days after treatment, with a control effect ≥90%: Compounds 11, 13, 209, 310, 485, 510, 511, 528, 554, 555, 556, 562, 566 , 568, 569, 579, 581, 599, 601, 606, 616, 617, 623, 627, 628, 630, 632, 635, 636, 639.

The following compounds have a good insecticidal effect at a concentration of 5 ppm, 3 days after the treatment, and the control effect is ≥90%: Compounds 4, 5, 281, 282, 309, 484, 526, 553, 600, 620, 621, 644, 649 , 650.

Bioassay Example 2

In this embodiment, the insecticidal activity test of Plutella xylostella is carried out, and the specific method is as follows:

The activity test was carried out by leaf-dip feeding. The leaf dish is immersed in the medicinal solution for 10s, and then dried in a petri dish, 4 dishes per dish, and filter paper is placed in the petri dish to moisturize. Ten dishes of Plutella xylostella were received in each dish and repeated three times. It was placed in a light incubator at a temperature of 25 ° C under 14hL: 10hD and cultured. The number of dead insects of Plutella xylostella was investigated at 1, 2 and 3 days after the administration, and the mortality was calculated.

The test results are as follows:

When the concentration of the following compounds is 10 ppm, the insecticidal effect on Plutella xylostella is better 3 days after the treatment, and the control effect is ≥90%: Compounds 2, 7, 9, 11, 12, 279, 527, 555, 558, 602, 607, 622, 623, 624, 625, 626, 637, 646.

When the concentration of the following compounds is 1 ppm, the insecticidal effect on Plutella xylostella is better 3 days after the treatment, and the control effect is ≥90%: Compounds 13, 60, 75, 76, 77, 78, 79, 80, 310, 484, 485, 510,528,536,537,556,579,599,600,606,616,617,621,628,632,633,634,635,636,639,644,645,649,650,673.

When the concentration of the following compounds is 0.4 ppm, the insecticidal effect on Plutella xylostella is better 3 days after the treatment, and the control effect is ≥90%: Compounds 4, 5, 45, 209, 281, 282, 309, 526, 553, 554, 620 , 627.

Bioassay Example 3

In this embodiment, the insecticidal activity test of Spodoptera litura is carried out, and the specific method is as follows:

The activity test was carried out by leaf-dip feeding. The leaf dish is immersed in the medicinal solution for 10s, and then dried in a petri dish, 4 dishes per dish, and filter paper is placed in the petri dish to moisturize. Ten dishes of Spodoptera litura were tested in each dish and repeated 3 times. It was placed in a light incubator at a temperature of 25 ° C under 14hL: 10hD and cultured. The number of dead insects of Spodoptera litura was investigated 3 days after the treatment, and the mortality was calculated.

The test results are as follows:

When the concentration of the following compounds is 10 ppm, the insecticidal effect on Spodoptera litura is better 3 days after the treatment, and the control effect is ≥90%: Compounds 4, 5, 11, 13, 209, 553, 554, 555, 566, 567, 568 , 569, 579, 599, 601, 623, 630, 673.

When the concentration of the following compounds is 1 ppm, the insecticidal effect on Spodoptera litura is better 3 days after the treatment, and the control effect is ≥90%: compounds 281, 282, 484, 526, 553, 600, 620, 644, 649, 650.

Bioassay Example 4

In this embodiment, the insecticidal activity test of Spodoptera exigua is carried out, and the specific method is as follows:

The activity test was carried out by leaf-dip feeding. The leaf dish is immersed in the medicinal solution for 10s, and then dried in a petri dish, 4 dishes per dish, and filter paper is placed in the petri dish to moisturize. Ten dishes of beet armyworm were received in each dish, and repeated 3 times. It was placed in a light incubator at a temperature of 25 ° C under 14hL: 10hD and cultured. The number of dead beetles of beet armyworm was investigated 3 days after the treatment, and the mortality was calculated.

The test results are as follows:

When the concentration of the following compounds is 10 ppm, the insecticidal effect on beet armyworm is better 3 days after the treatment, and the control effect is ≥90%: Compounds 5,282,484,526,553,568,600,644,649,650,673 .

When the concentration of the following compounds is 1 ppm, the insecticidal effect on Spodoptera exigua will be better 3 days after the treatment, and the control effect will be ≥90%: Compounds 4,281, 11, 13, 209, 484, 526, 553, 554, 555, 566 , 569, 579, 599, 601, 620, 623, 630.

Test Example 5

In this example, the indoor biological activity of the compound against the armyworm is tested, and the specific method is as follows:

The corn seedling feeding method was used for the activity test. Cut the above-ground part of fresh corn seedlings grown indoors, about 10cm, and set aside. The corn seedlings were immersed in the medicinal solution for 10s, and after being dried in a cool place, cut into 3 to 5 cm leaf sections, and placed in a petri dish, and placed 3 corn seedlings per dish. Ten 10th instar larvae of the armyworm were inserted into each well and repeated three times. Place in a light incubator at 25 ° C, and culture in the dark. 1,2,3 days after treatment, the reaction symptoms were investigated, and the mortality was calculated.

When the concentration of some of the compounds of the present application is 1 ppm, the control effect on the armyworm (ie, the mortality of the armyworm) is ≥90% 3 days after the medicine, and the serial numbers of the compounds are: 2, 4, 5, 9, 11, 12, 13, 45, 168, 278, 281, 282, 309, 510, 526, 527, 528, 536, 554, 555, 556, 562, 566, 567, 569, 579, 599, 600, 601, 606, 607, 620, 623, 624, 625, 626, 630, 637, 640, 644, 645, 646, 649, 650, 673.

Test Example 6

Biological activity of test compounds against thrips on soybeans in this example (greenhouse)

Test time: 2018.05.25 ～ 2018.06.07

Test system: Thrips populations that naturally occur on soybeans grown in greenhouses, with a base of occurrence greater than 100 heads per compound leaf, and thrips are in the active phase. (Sensitivity of the population to the medicament. Monitoring results under the same conditions: ethyl polysterilization 50mg / L dose of 66.55% after 6 days).

Area of the plot: 10m ² , no repeats.

Test agent: 5% SL (compound 5% + emulsifier 5% + solvent make up 100%) for each compound.

Method: Spray treatment of stems and leaves.

① Application time: Thrips is in the period of adult and larval activity, and the number of applications: 1 time.

② Water consumption: Based on the dose mg / kg, the stems and leaves are sprayed with moist drips from the upper leaves.

③Investigation indicators: Investigate the number of thrips on the leaves, count 1 leaf with 3 single leaf compound leaves, and randomly investigate 3 leaves.

④ Investigation time and frequency: 2 days and 6 days after the drug investigation respectively, a total of 2 investigations.

Results and analysis The field activity results of compound 281 on soybean thrips are shown in Table 14.

Table 14 Field activity of compound 4 on soybean yellow thrips (Shanghai Qingpu, 2018.06)

Bioassay Example 5

In this example, it is verified that the pharmaceutical composition containing the active ingredient compound 616 and beta-cypermethrin has a synergistic effect on cotton bollworm.

(1) Purpose: To test the indoor virulence activity of a composition containing the effective ingredient compound 616 and lambda-cyhalothrin against cotton bollworm, and evaluate the type of combined action of the effective ingredient compound 616 and lambda-cyhalothrin.

(2) Method: Soaking method

① Test target: cotton bollworm, 3rd instar larva.

② Drug configuration: Drug name: Compound 616, beta-cyhalothrin, both of which are the original drugs.

Mother liquor preparation: According to the proportion and dosage of the test design, weigh a certain amount of the original drug, dissolve it with N, N-dimethylformamide (DMF), and then add 0.05% Tween 80 water to prepare a mother liquor of a certain concentration.

Preparation of medicinal solution: 5 to 7 doses are set for each ratio. According to the design of the experiment, the mother liquor is diluted to the test dose in turn.

③ Chemical treatment: immerse the cotton bollworm larva in the medicinal solution for 10s, and then put the test insects into a 24-well plate with feed, one per well, and 24 test insects per treatment. When dipping, the same medicament is performed in order from low concentration to high concentration, and a blank control and a solvent control are set.

After treatment, it was placed in a light incubator at a temperature of 25 ± 1 ℃ and a light-dark ratio of 15h: 9h.

④ Results investigation: The number of dead insects was investigated 3 days after the treatment.

⑤ Data processing: DPS (v16.05) statistical analysis software was used to calculate the LC ₅₀ value of each drug and its 95% confidence limit.

The co-toxicity coefficient (CTC value) of the mixture is calculated according to formula (1), formula (2), and formula (3):

In the formula: ATI-mixture measured virulence index;

S—LC _{50 of} standard pesticides in milligrams per liter (mg / L);

LC _{50 of} M-mixture, unit is milligram per liter (mg / L).

TTI = A × PA + B × PB ............................................................... ··························(2)

In the formula: TTI-mixture theoretical virulence index;

A—A pharmaceutical toxicity index;

The percentage content of PA-A agent in the mixture, the unit is percentage (%);

B—B pharmaceutical toxicity index;

The percentage content of PB-B agent in the mixture, the unit is percentage (%).

In the formula: CTC—co-toxicity coefficient; ATI—mixture measured virulence index; TTI—mixture theoretical virulence index.

The co-toxicity coefficient (CTC) ≥ 120 of the compounding agent is synergistic; CTC ≤ 80 is antagonistic; 80 <CTC <120 is additive.

(3) The results are shown in Table 15

Table 15 Co-toxicity statistics on the 3rd instar larvae of cotton bollworm (3d after treatment)

(4) Evaluation of the combined effect of the composition: The results show that compound 616 and lambda-cyhalothrin have good activity against cotton bollworm; compound 616 and lambda-cyhalothrin are mixed, 60: 1 ～ 1: 60 The synergistic coefficients of each ratio are 91-139, all of which show an additive or synergistic effect; at a ratio of 60: 1 to 1: 3, they appear synergistic effects.

Bioassay Example 6

In this example, it is verified that the composition containing the active ingredient compound 627 and avermectin has a synergistic effect on diospyridine

(1) Purpose: To test the indoor virulence activity of a composition containing the effective ingredient compound 627 and avermectin on pupae, and to evaluate the type of combined action of the effective ingredient compound 627 and avermectin.

(2) Method: Rice stem dipping method

① Test target: Pupae diploid, 3rd instar larva.

② Drug configuration: drug name: compound 627, avermectin, are the original drug.

Mother liquor preparation: According to the proportion and dosage of the test design, weigh a certain amount of the original drug, dissolve it with N, N-dimethylformamide (DMF), and then add 0.05% Tween 80 water to prepare a mother liquor of a certain concentration.

Preparation of medicinal solution: 5 to 7 doses are set for each ratio. According to the design of the experiment, the mother liquor is diluted to the test dose in turn.

③ Medicament treatment: immerse the prepared rice stems in the medicinal solution for 10s, dry them and put them into finger tubes, and then put the test insects into the finger tubes with rice stems, 10 heads per tube, each treatment 30 Head test insect. When dipping, the same medicament is performed in order from low concentration to high concentration, and a blank control and a solvent control are set. After treatment, it was placed in a light incubator at a temperature of 28 ± 1 ℃ and a light-dark ratio of 16h: 8h.

④ Results investigation: The number of dead insects was investigated 3 days after the treatment.

⑤ Data processing: DPS (v16.05) statistical analysis software was used to calculate the LC ₅₀ value of each drug and its 95% confidence limit.

The co-toxicity coefficient (CTC value) of the mixture is calculated according to the formula of the biological test example 1:

The co-toxicity coefficient (CTC) ≥ 120 of the compounding agent is synergistic; CTC ≤ 80 is antagonistic; 80 <CTC <120 is additive.

(3) The results are shown in Table 16.

Table 16 Statistics on the co-toxicity coefficients of the 3rd instar larvae of pupae (2d)

(4) Evaluation of the combined action of the composition

The results showed that both compound 627 and avermectin had good activity on dioscorea. The compound of compound 627 and avermectin had a synergy coefficient of 91-180 for each ratio of 100: 1 to 1: 100. It appears as an additive or synergistic effect; it appears as a synergistic effect at a ratio of 50: 1 to 1:10.

Bioassay example 7

In this example, it was verified that the composition containing the active ingredient compound 628 and indoxacarb had synergistic effects on Spodoptera exigua.

(1) Objective: To test the indoor virulence activity of a composition containing the active ingredient compound 628 and indoxacarb against Spodoptera exigua, and evaluate the type of combined action of the active ingredient compound 628 and indoxacarb.

(2) Method: soaking leaf method

① Test target: Spodoptera exigua, 4th instar larva.

② Drug configuration: Drug name: Compound 628, indoxacarb, are the original drug.

Mother liquor preparation: According to the proportion and dosage of the test design, weigh a certain amount of the original drug, dissolve it with N, N-dimethylformamide (DMF), and then add 0.05% Tween 80 water to prepare a mother liquor of a certain concentration. Preparation of medicinal solution: 5 to 7 doses are set for each ratio. According to the design of the experiment, the mother liquor is diluted to the test dose in turn.

③ Medicament treatment: immerse the leaf dish in the medicinal solution for 10s, dry it and put it into a 24-well plate. One test insect is connected to each well, and 24 test insects are processed. When dipping, the same medicament is performed in order from low concentration to high concentration, and a blank control and a solvent control are set.

After treatment, place it in a light incubator at a temperature of 27 ± 1 ° C.

④ Results investigation: The number of dead insects was investigated 3 days after the treatment.

⑤ Data processing: DPS (v16.05) statistical analysis software was used to calculate the LC ₅₀ value of each drug and its 95% confidence limit.

The co-toxicity coefficient (CTC value) of the mixture is calculated according to the formula of the biological test example 1:

The co-toxicity coefficient (CTC) ≥ 120 of the compounding agent is synergistic; CTC ≤ 80 is antagonistic; 80 <CTC <120 is additive.

(3) The results are shown in Table 17.

Table 17 Statistics on co-toxicity coefficients of 4th instar larvae of Spodoptera exigua (3d after treatment)

(4) Evaluation of the combined effect of the composition: The results show that compound 628 and indoxacarb have good activity against Spodoptera exigua; compound 628 and indoxacarb are compounded, and the ratios of 40: 1 to 1:40 increase. The coefficient of effectiveness is 106 to 227, all of which show an additive or synergistic effect; at a ratio of 30: 1 to 1: 5, they exhibit a synergistic effect.

Bioassay Example 8

In this example, it was verified that the composition containing the active ingredient compound 632 and clothianidin had a synergistic effect on brown planthoppers

(1) Purpose: To test the indoor virulence activity of a composition containing the active ingredient compound 632 and clothianidin on brown planthoppers, and to evaluate the type of combined action of the active ingredient compound 632 and clothianidin.

(2) Method: Rice seedling dipping method

① Test target: brown planthopper, 3rd instar nymph.

② Drug configuration: Drug name: Compound 632, clothianidin, are the original drug. Mother liquor preparation: According to the proportion and dosage of the test design, weigh a certain amount of the original drug, dissolve it with N, N-dimethylformamide (DMF), and then add 0.05% Tween 80 water to prepare a mother liquor of a certain concentration.

Preparation of medicinal solution: 5 to 7 doses are set for each ratio. According to the design of the experiment, the mother liquor is diluted to the test dose in turn.

③Pharmacy treatment:

The rice seedlings were immersed in the medicinal solution for 10s, and then filled into disposable cups. Each cup received 15 insects, sealed with plastic wrap, and treated 45 test insects. When dipping, the same medicament is performed in order from low concentration to high concentration, and a blank control and a solvent control are set.

After the treatment, it was placed in a light incubator at a temperature of 28 ± 1 ℃ and a light-dark ratio of 15h: 9h.

④ Results investigation

The number of dead insects was investigated 3d after the treatment.

⑤ Data processing

The DPS (v16.05) statistical analysis software was used to calculate the LC ₅₀ value of each agent and its 95% confidence limit.

The co-toxicity coefficient (CTC value) of the mixture is calculated according to the formula of the biological test example 1:

The co-toxicity coefficient (CTC) ≥ 120 of the compounding agent is synergistic; CTC ≤ 80 is antagonistic; 80 <CTC <120 is additive.

(3) The results are shown in Table 18.

Table 18 Statistics on the co-toxicity coefficients of the 3rd instar nymphs of the brown planthopper (3d after treatment)

(4) Evaluation of the combined effect of the composition: The results show that compound 632 and clothianidin have good activity against brown planthoppers; compound 632 and clothianidin have a synergistic coefficient of 60: 1 to 1:60 in each combination From 101 to 296, they all showed additive or synergistic effects; at the ratio of 40: 1 to 1:40, they showed synergistic effects.

Bioassay Example 9

In this example, it is verified that the composition containing the active ingredient compound 627 and thiamethoxam has a synergistic effect on alfalfa

(1) Purpose: To test the indoor virulence activity of a composition containing the effective ingredient compound 627 and thiamethoxam on alfalfa aphid, and evaluate the type of combined action of the effective ingredient compound 627 and thiamethoxam.

(2) Method: Soaking method

① Test target: alfalfa aphid, 3-day-old nymph.

② Drug configuration: drug name: compound 627, thiamethoxam, are the original drug. Mother liquor preparation: According to the proportion and dosage of the test design, weigh a certain amount of the original drug, dissolve it with N, N-dimethylformamide (DMF), and then add 0.05% Tween 80 water to prepare a mother liquor of a certain concentration.

Preparation of medicinal solution: 5 to 7 doses are set for each ratio. According to the design of the experiment, the mother liquor is diluted to the test dose in turn.

③ Medicinal treatment: immerse the nymph leaves in the medicinal solution for 10s, insert it into a penicillin bottle filled with water, seal it, dry it, cover it with a transparent plastic cup, repeat 15 to 30 aphids each time, and repeat the treatment 3 times. When dipping, the same medicament is performed in order from low concentration to high concentration, and a blank control and a solvent control are set. After the treatment, it was placed in an observation room with an indoor temperature of 19 to 26 ° C., a humidity of 35% to 65%, and a culture rack with 14Lh: 10Dh light.

④ Results investigation: The number of dead insects was investigated 3 days after the treatment.

⑤ Data processing: DPS (v16.05) statistical analysis software was used to calculate the LC ₅₀ value of each drug and its 95% confidence limit.

The co-toxicity coefficient (CTC value) of the mixture is calculated according to the formula of the biological test example 1:

The co-toxicity coefficient (CTC) ≥ 120 of the compounding agent is synergistic; CTC ≤ 80 is antagonistic; 80 <CTC <120 is additive.

(3) The results are shown in Table 19.

Table 19 Statistics on co-toxicity coefficients of alfalfa aphids 3 days old nymphs (3d after treatment)

(4) Evaluation of the combined effect of the composition: The results show that compound 627 and thiamethoxam have good activity on alfalfa aphid; compound 627 and thiamethoxam are mixed, and the synergism of each ratio of 60: 1 to 1:10 is synergistic. The coefficients are 89 ～ 312, all of which appear as additive or synergistic effects; at the ratio of 1: 3-20: 1, they appear synergistic effects.

Bioassay Example 10

In this example, it is verified that the composition containing the active ingredient compound 510 and diphenylhydrazide has a synergistic effect on Tetranychus cinnabarinus

(1) Objective: To test the indoor virulence activity of a composition containing the effective ingredient compound 510 and diphenylhydrazide to Tetranychus cinnabarinus, and to evaluate the type of combined action of the effective ingredient compound 510 and diphenylhydrazide.

(2) Method: Soaking method

① Test target: Tetranychus cinnabarinus, adult mite.

② Drug configuration: Drug name: Compound 510, biphenylhydrazine ester, are the original drug.

Mother liquor preparation: According to the proportion and dosage of the test design, weigh a certain amount of the original drug, dissolve it with N, N-dimethylformamide (DMF), and then add 0.05% Tween 80 water to prepare a mother liquor of a certain concentration. Preparation of medicinal solution: 5 to 7 doses are set for each ratio. According to the design of the experiment, the mother liquor is diluted to the test dose in turn.

③ Medicament treatment: immerse the mite-leaving leaf in the medicinal solution for 10s, insert it into a penicillin bottle filled with water, seal it, dry it, and cover it with a transparent plastic cup. Each repetition is 15 or more mites, and each treatment is repeated 3 times. . When dipping, the same medicament is performed in order from low concentration to high concentration, and a blank control and a solvent control are set. After the treatment, it was placed in an observation room with an indoor temperature of 19 to 26 ° C., a humidity of 35% to 65%, and a culture rack with 14Lh: 10Dh light.

④ Results investigation: The number of dead mites was investigated 3 days after the treatment.

⑤ Data processing: DPS (v16.05) statistical analysis software was used to calculate the LC ₅₀ value of each drug and its 95% confidence limit.

The co-toxicity coefficient (CTC value) of the mixture is calculated according to the formula of the biological test example 1:

The co-toxicity coefficient (CTC) ≥ 120 of the compounding agent is synergistic; CTC ≤ 80 is antagonistic; 80 <CTC <120 is additive.

(3) The results are shown in Table 20.

Table 20 Statistics of co-toxicity coefficients against adult spider mites, C. cinnabarinus (3d after treatment)

(4) Evaluation of the combined effect of the composition: The results show that both compound 510 and biphenylhydrazide have good activity against adult spider mites, Tetranychus cinnabarinus; compound 510 and biphenylhydrazide are compounded at a ratio of 50: 1 to 1:50. The synergistic coefficient is 81-158, all of which show an additive or synergistic effect; the synergistic effect is shown at a ratio of 1:15 to 5: 1.

Bioassay Example 11: The composition of active ingredient A is a compound of formula I and active ingredient B is avermectin, methylamino avermectin benzoate, ethyl spinosad, etc. Activity test

Target: 3rd instar larvae of pupae, indoor breeding.

Method: Rice stem dipping method. METHODS Same as bioassay example 1. The evaluation methods and standards are as follows:

Synergistic effect = actual mortality%-theoretical mortality%

Theoretical mortality = 1-(1-mortality of active ingredient A at this dose) (1-mortality of active ingredient B at this dose)

Synergistic effect ≥20 means significant synergy; 10≤ synergistic effect <20, synergistic effect; -10≤ synergistic effect <10, synergistic effect; synergistic effect <-10, antagonistic, negative value The greater the degree of antagonism.

The results are shown in Table 21. From the results, it can be seen that the effective ingredient A is compound 616, which has excellent activity on pyrene disulfide; the effective ingredient B is avermectin, methylamino avermectin benzoate, ethyl poly When it is bactericidin, it has excellent activity on dioxin; when A and B are combined, the combined effect is synergistic.

Table 21 Insecticidal activity of the test reagents against pupae

Bioassay Example 12: Active ingredient A is a compound of formula I and active ingredient and B is methylamino Avermectin benzoate, chlorantraniliprole, etc., and its activity is tested against slimeworms

Methods: Soaking method. The operation description is as follows: With reference to NY / 1154.6-2006, the main operation description is as follows: immerse 10 test insects in the medicinal solution for 10s, dry them and place them in petri dishes, put 4 clean corn leaf sections in each dish, and petri dishes Put filter paper inside to moisturize. 3 repetitions. It was placed in a light incubator at a temperature of 25 ° C under 14hL: 10hD and cultured. The number of dead and live insects of the armyworm was investigated 3 days after the administration, and the mortality was calculated.

The evaluation method was the same as that in Example 11.

The results are shown in Table 22. From the results, it can be seen that when the active ingredient A is compounds 9, 13, 60, 75, 209, 387, 611, 624, 644, 673, it has excellent activity against the armyworm; the effective ingredient B is Methylamino Avermectin Benzoate, Chlorantraniliprole, Diflubenzuron, Flufenazone, Indoxacarb, Indoxacarb, Tetrabenzuron, Cyflufenamid, and Amidacid Has excellent activity; when A and B are combined, the combined effect appears to be synergistic or significant synergistic.

Table 22 Insecticide activity against testworms in laboratory

The applicant states that the present application uses the above examples to describe the pharmaceutical composition containing the metadiamide compound and its application, but this application is not limited to the above examples, which does not mean that this application must rely on the above implementation Cases can be implemented. Those skilled in the art should understand that any improvement to this application, equivalent replacement of each raw material of the product of this application, addition of auxiliary components, selection of specific methods, etc., all fall within the scope of protection and disclosure of this application.

Claims (18)

1. A pharmaceutical composition containing a metadiamide compound, wherein the pharmaceutical composition includes an active ingredient A and an active ingredient B, the active ingredient A is an amide compound having a structure represented by Formula I, and the active ingredient B Including any one or a combination of other fungicides, insecticides or acaricides;

   

   Wherein Z is selected from hydrogen, fluorine, chlorine, bromine, iodine, cyano, nitro, hydroxyl, substituted or unsubstituted 3-10 membered heterocyclic group, C ₁ -C ₆ alkyl, C ₁ -C ₆ haloalkane , C ₁ -C ₆ alkoxy, C ₁ -C ₆ haloalkoxy, C ₁ -C ₆ alkylsulfinyl, C ₁ -C ₆ haloalkylsulfinyl, C ₁ -C ₆ alkylsulfonyl Acyl or C ₁ -C ₆ haloalkylsulfonyl; Q is selected from C ₃ -C ₈ cycloalkyl or C ₃ -C ₈ halocycloalkyl; X is selected from hydrogen, fluorine or trifluoromethyl; Y _{1 is} selected From fluorine, chlorine, bromine, iodine, cyano, nitro, C ₁ -C ₆ alkyl, C ₁ -C ₆ haloalkyl, C ₁ -C ₆ haloalkoxy, C ₂ -C ₄ alkenyl, C ₂ -C ₄ haloalkenyl, C ₂ -C ₄ alkynyl, C ₂ -C ₄ haloalkynyl, C ₃ -C ₈ cycloalkyl, C ₃ -C ₈ halocycloalkyl, C ₁ -C ₆ alkylcarbonyl, C ₁ -C ₆ alkylsulfinyl, C ₁ -C ₆ haloalkylsulfinyl, C ₁ -C ₆ alkylsulfonyl or C ₁ -C ₆ haloalkylsulfonyl; Y ₂ selected From chlorine, bromine, iodine, cyano, nitro, C ₁ -C ₆ haloalkyl, C ₁ -C ₆ haloalkoxy, C ₂ -C ₄ alkenyl, C ₂ -C ₄ haloalkenyl, C ₂ -C ₄ alkynyl, C ₂ -C ₄ haloalkynyl, C ₃ -C ₈ cycloalkyl, C ₃ -C ₈ Generation cycloalkyl, C ₁ -C ₆ alkylcarbonyl, C ₁ -C ₆ alkylsulfinyl, C ₁ -C ₆ haloalkylsulfinyl group, C ₁ -C ₆ alkylsulfonyl or C ₁ -C ₆ haloalkylsulfonyl; R _{1 is} selected from hydrogen, fluorine or methoxy; R _{2 is} selected from fluorine or trifluoromethyl; R ₃ and R ₄ are each independently selected from hydrogen, halogen, cyano, nitro, C _1- C ₆ alkyl, C ₁ -C ₆ haloalkyl, C ₃ -C ₈ cycloalkyl or C ₃ -C ₈ halocycloalkyl; m represents an integer from 0 to 5; n represents an integer from 0 to 3 ; W ₁ and W _{2 are} independently an oxygen atom or a sulfur atom.
2. The pharmaceutical composition according to claim 1, wherein the heterocyclic group is selected from the group consisting of oxadiazolyl, oxazolyl, isoxazolyl, isoxazoline, pyrazolyl, Pyrazolinyl, furyl, thienyl, pyridyl, pyrimidinyl, pyridazinyl, pyrazinyl, benzoxazolyl, benzothiazolyl, benzimidazolyl, benzothiadiazolyl, quinoline Group, isoquinolinyl, quinoxaline or quinazoline.
3. The pharmaceutical composition containing m-lactam compound according to claim 1, wherein said 3-10 membered heterocyclyl group substituted by R ₅ substituted 3-10 membered heterocyclyl, R ₅ is selected from the Hydrogen, halogen, cyano, nitro, C ₁ -C ₆ alkyl, C ₁ -C ₆ haloalkyl, C ₁ -C ₆ alkoxy or C ₁ -C ₆ haloalkoxy.
4. The pharmaceutical composition according to claim 1, wherein Z is selected from the group consisting of hydrogen, fluorine, chlorine, bromine, iodine, cyano, nitro, hydroxyl, 3-10 membered heterocyclic group, and at least 1 R ₅ substituted 3-10 membered heterocyclyl, C ₁ -C ₆ alkyl, C ₁ -C ₆ haloalkyl, C ₁ -C ₆ alkoxy, C ₁ -C ₆ haloalkoxy, C ₁ -C ₆ alkylsulfinyl, C ₁ -C ₆ haloalkylsulfinyl, C ₁ -C ₆ alkylsulfonyl or C ₁ -C ₆ haloalkylsulfonyl; Q is selected from C ₃ -C ₈ cycloalkane Or C ₃ -C ₈ halocycloalkyl; X is selected from hydrogen or fluorine; Y _{1 is} selected from fluorine, chlorine, bromine, iodine, cyano, nitro, C ₁ -C ₆ alkyl, C ₁ -C ₆ haloalkyl, C ₁ -C ₆ haloalkoxy; Y _{2 is} selected from chlorine, bromine, iodine, cyano, nitro, C ₁ -C ₆ alkyl, C ₁ -C ₆ haloalkyl, C ₁ -C ₆ Haloalkoxy C ₁ -C ₆ alkylcarbonyl, C ₁ -C ₆ alkylsulfinyl, C ₁ -C ₆ haloalkylsulfinyl, C ₁ -C ₆ alkylsulfonyl or C ₁ -C ₆ haloalkane R _{1 is} selected from hydrogen, fluorine or methoxy; R _{2 is} selected from fluorine or trifluoromethyl; R ₃ and R ₄ are each independently selected from hydrogen, halogen, cyano, nitro, C _1- C ₆ alkyl , C ₁ -C ₆ haloalkyl, C ₃ -C ₈ cycloalkyl or C ₃ -C ₈ halocycloalkyl group; R ₅ is selected from hydrogen, halo, cyano, nitro, C ₁ -C ₆ alkyl , C ₁ -C ₆ haloalkyl, C ₁ -C ₆ alkoxy or C ₁ -C ₆ haloalkoxy; m represents an integer from 0 to 5; n represents an integer from 0 to 3; W ₁ and W _{2 are} independently It is an oxygen atom or a sulfur atom.
5. The pharmaceutical composition containing an m-diamide compound according to claim 1, wherein Z is selected from the group consisting of hydrogen, fluorine, chlorine, bromine, iodine, cyano, nitro, hydroxyl, methoxy, methyl, and trifluoromethyl Methyl, pentafluoroethyl, heptafluoroisopropyl, difluoromethoxy, trifluoromethoxy, methylsulfinyl, trifluoromethylsulfinyl, methanesulfonyl, trifluoromethanesulfonyl or 5 -Trifluoromethyl-1,2,3-thiadiazol-3-yl; m represents an integer from 0 to 5; Q is selected from cyclopropyl, 1-chlorocyclopropyl, 1-fluorocyclopropyl , cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl or cyclooctyl; X is selected hydrogen; Y ₁ selected from bromo, iodo, trifluoromethyl, pentafluoroethyl, heptafluoroisopropyl or Trifluoromethoxy; Y ₂ selected from chlorine, bromine, iodine, cyano, nitro, methyl, ethyl, isopropyl, tert-butyl, acetyl, trifluoroacetyl, propionyl, isopropylamide , Trifluoromethyl, pentafluoroethyl, heptafluoroisopropyl, trifluoromethoxy, methylsulfinyl, trifluoromethylsulfinyl, methanesulfonyl or trifluoromethanesulfonyl; R ₁ selected from hydrogen, fluoro or methoxy; R ₂ is selected from fluoro; R ₃ and R ₄ are each independently selected from hydrogen Fluorine, chlorine, bromine, iodine, cyano, nitro, methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, tert-butyl, n-pentyl, 2-pentyl, neo Pentyl, isopentyl, 4-methyl-2-pentyl, n-hexyl, monofluoromethyl, difluoromethyl, trifluoromethyl, monochloromethyl, dichloromethyl, trichloromethyl, Pentafluoroethyl, heptafluoroisopropyl, cyclopropyl, cyclobutyl, cyclopentyl, perfluorocyclopropyl, perfluorocyclobutyl or perfluorocyclopentyl; W ₁ and W ₂ are Oxygen atom.
6. The pharmaceutical composition containing an m-diamide compound according to claim 1, wherein in the formula I, Z is selected from the group consisting of hydrogen, fluorine, chlorine, bromine, iodine, cyano, nitro, trifluoromethyl, and pentafluoro Ethyl, heptafluoroisopropyl, difluoromethoxy, trifluoromethoxy, methylsulfinyl, trifluoromethylsulfinyl, methanesulfonyl, or trifluoromethanesulfonyl; m represents 0 to 5 An integer of Q, selected from cyclopropyl 1-chlorocyclopropyl; Y ₁ selected from bromine or iodine; Y ₂ selected from bromine, methyl, isopropyl, tert-butyl, acetyl, trifluoromethyl or Trifluoromethoxy; R _{1 is} selected from hydrogen, methoxy or fluorine; R _{2 is} selected from fluorine; R ₃ and R ₄ are each independently selected from hydrogen, chlorine, methyl, monochloromethyl, trifluoromethyl Or cyclopropyl, W ₁ and W ₂ are oxygen atoms.
7. The pharmaceutical composition containing a metadiamide compound according to any one of claims 1-6, wherein the metadiamide compound is any one or a combination of at least two selected from the following compounds:

   

   

   

   

   

   
8. The pharmaceutical composition containing a metadiamide compound according to any one of claims 1 to 7, wherein the active ingredient B is selected from the group consisting of nicotine, rotenone, veratrine, matrine, matrine, Mineral oil, imidacloprid, thiamethoxam, imidacloprid, clothianidin, clothianidin, acetamiprid, nitenpyram, furacid, piperidin, chlorothiline, flufenapyronitrile, flufendi Carbendiamide, triflumezopyrim, flupyradifurone, spinosyn, ethyl spinosad, chlorpyrifos, methyl chlorpyrifos, dimethoate, omethoate, dichlorvos, triazophos, phoxim, thiazophos, diaziphos, malathion Phosphorus, acephate, thiophosphine, fenitrothion, parathion, profenfos, endosulfan, pyracronitrile, chlorpyramid, trimethoprim, prothiocarb, metronid Carbamazepine, carbamazepine, aldicarb, chlorhexidine, thiodicarb, methiocarb, menadicarb, isoprocarb, secbutacarb, fipronil, fipronil, ethiprole, permethrin, Cypermethrin, dextranmethrin, tefluthrin, tefluthrin, deltamethrin, cypermethrin, cypermethrin, Z-cypermethrin, Cyhalothrin, Permethrin, Permethrin, Tetramethrin, Permethrin, Cyfluthrin, Bifenthrin, Allmethrin, Permethrin, Permethrin Esters, fenvalerate, fenvalerate, S-fenvalerate, fenvalerate, tefluthrin, fenvalerate, permethrin, beta-cypermethrin, refined beta-cypermethrin, pyrethrin, arsenal Avermectin, avermectin benzoate, pyriproxyfen, phenoxycarb, pymetrozine, tetramazine, thiazinone, thiafenidone, ethiprole, flubendicarb, fenuron , Fluflubenzuron, Fluflumicarbazone, Diflubenzuron, Butylurea, Mildecarbazone, Flufenazone, Fluorylurea, Flubenzuron, Cyclofenazid, Methofenazide, Insectrazide, Furans Hydrazide, pyraclostrobin, fenaquinone, fenapyr, acetazolonitrile, fenflufen, bifenazate, azoxyfen, pyrimidin, pyraclostrobin, pyraclostrobin, flufenazone , Dicofol, bromofenat, trimethoxam, phentermin, dimethylformamide, pyraclostrobin, indoxacarb, cyanfludizone, spirotetramat, spirotetramat, spiropidion, chlorfenben Formamide, flubendiamide, and cyprofenil , Cyclobromide, Tetrachloropyramid, Tetraniliprole, Insecticidal Single, Insecticidal Double, Raptan, Azadirachtin, Bacillus thuringiensis, Bacillus robustus, Bacillus sphaericus, Acetyl mite, Tetraacetaldehyde, isocycloseram , Tyclopyrazoflor, flupyrimin, oxazosulfyl, benzpyrimoxan, fluazaindolizine, fluxametamide, dicloromezotiaz, tioxazafen, fluensulfone, fluhexafon, pyrifluquinazon, prothioconazole, fenpropiazole, fluoxazole, enazol, nitrilazole, flusilazole, Fenconazole, Tebuconazole, Tebuconazole, Paclobutanil, Penconazole, Propiconazole, Tetraflurane, Triazole, Biphenyltriazole, Triazolone, Azoxystrobin, Tetrafenil , Oxystrobin, picoxystrobin, pyraclostrobin, fluoxastrobin, trisoxystrobin, syringarestrobin, enazoxystrobin, enazoxystrobin, azoxystrobin, metalaxyl, methaxam Moraxantine, flubendiamide, thiafuramide, bifenapram, flubendiamide, fenpropenil, flubendiamide, fluoxastrobin, fluoxastrobin, pyraclostrobin, flubendicarb Paclosporin, fluamide, valprocarb, thiazolid, diacetylenic bacteria , Boscalid, fluoxastrobin, blasticillamide, veracil, fluthiazolyl, thiabendazole, imazalil, prochloraz, blasticid, acetonitrile, fluconazole, rot Mildew, Isocarbazone, Vinyl Sclerotin, Clodiazol, Sclerotia sclerotia, Crimsoncarb hydrochloride, etimicarb, carbendazim, benomyl, methylthiocarbam, jinggangmycin, medium Bacteriocin, streptomycin sulfate, polyoxin, kasugamycin, wuningmycin, oxacillin, oxaphene, dimethomorph, flumorph, tridemorph, azoxystrobin, Pyrimethanil, acetaminophen, dicyananthraquinone, Daisenlian, Fumeishuang, Zinc and Zinc, Zinc and Zinc, Zinc, Zinc, Phosphon, Aluminum , Tricyclazole, pentachloronitrobenzene, carbostyronitrile, flupronil, sodium disulfonate, fluazinam, copper thiazole, potassium dihydrogen phosphate, sulfur, copper hydroxide, activated ester, or fluoxazole activated ester Any one or a combination of at least two.
9. The pharmaceutical composition containing a metadiamide compound according to claim 8, wherein when the active ingredient A is selected from the following compounds,

   

   

   B is not selected from the group consisting of avermectin, methylaminoavermectin benzoate, spinosyn, ethyl spinosad, ivermectin, mibemycin, thiamethoxam, imidacloprid, clothianidin, Clothianidin, acetamiprid, nitenpyram, dipyridam, epoxipyram, flupurone, flufenacil, nitrflufenid, pymetrozine, thiazidone, trifluorobenzimid , Dichlorothiapyrimidine, diprofen, pyrifluquinazon, benzpyrimoxan, anisoleconazole, tebuconazole, prothioconazole, cyclopropazol, azoxystrobin, oxystrobin, pyraclostrobin , Picoxystrobin, metalaxyl, metalaxyl, flupronil, prochloraz, cyprodin, polyoxin, Jinggangmycin, kasugamycin, zotocin, thiamethoxam, Imidacloprid, clothianidin, clothianidin, acetamiprid, nitenpyram, diflubenzuron, epoxifen, flupyramid, flubendicarb, flubendicarb, acetamiprid, thiamethoxam Ketones, trifluorobenzimid, dichlorothiapyrimidine, diprofen, pyrifluquinazon, benzpyrimoxan, anisole, tebuconazole, tebuconazole, prothioconazole, cyclopropazol, azoxystrobin, oxystrobin , Fenoxystrobin, picoxystrobin, metalaxyl, metalaxyl, flupronil, prochloraz, cyprodin, chlorantraniliprole, flubendiamide, bromocyanid, tetrachloro Intrapyramid, Tetrabenpyramid, Chlorflufenamid, Cyclofazone, Fluoxazolamide, Fipronil, Acetofen, Acetoniprole, Indoxacarb, Tetrabenzuron, Tetrabenzuron, Tebufenac Carbendiamide, chlorfenuron, methoxid, acetamiprid, chlorpyrifos, acephate, phoxim, dichlorvos, fenthion, fenprofen, triazophos, beta-cyhalothrin , Deltamethrin, cypermethrin, bifenthrin, permethrin, permethrin, lavalin, deltamethrin, permethrin, bifenthrin, permethrin, permethrin, Insecticidal, insecticidal double, insecticidal ring, carbendazim, diflubenzuron, flubenzuron, imazapyr, pyriproxyfen or fenzozide.
10. The medicinal composition containing a metadiamide compound according to claim 8, wherein the active ingredient B is selected from the group consisting of imazafen, thiamethoxam, clothianidin, imidacloprid, acetamiprid, nitenpyram, furan Fipronil, flubendicarb, triflumezopyrim, flupyradifurone, spinosyn, etoxanthin, chlorpyrifos, triazophos, chlorfenapyr, fipronil, fipronil, ethiprole, Deltamethrin, beta-cypermethrin, beta-cyfluthrin, bifenthrin, fenvalerate, fenvalerate, tefluthrin, beta-cypermethrin, avermectin, avermectin Benzoate, pymetrozine, ethiprole, flubenzuron, fenflubenzuron, fluazinam, diflubenzuron, butylurea, flubenzuron, chlorfenuron, methoxyfenozide, fenzozide , Furanyl hydrazide, acetonitrile, acetazolonitrile, fenflufene, bifenazate, pyridaben, triazotin, phentermin, dimethylformamidine, indoxacarb, cyanfludizone , Chlorantraniliprole, flubendiamide, bromocyanide, cypromethoxam, tetrachloropyramid, insecticidal single, insecticidal double, fenitrothion, su Yun Bacillus, Bacillus sphaericus, alkynemite, isocycloseram, tyclopyrazoflor, flupyrimin, oxazosulfyl, benzpyrimoxan, fluazaindolizine, fluxametamide, dicloromezotiaz, tioxazafen, fluensulfone, fluhexafon, pyrifluquinazon, flurazole Azoxystrobin, hexazol, jinggangmycin, kasugamycin, tricyclazole, azoxystrobin, oxystrobin, picoxystrobin, pyraclostrobin, prochloraz, prochlorazin, veracol, Any one or a combination of at least two of metalaxyl, metalaxyl, benzimid, fluoxastrobin, or fluoxamide.
11. The medicinal composition containing a metadiamide compound according to claim 8, wherein the active ingredient B is selected from the group consisting of imazafen, thiamethoxam, imidacloprid, acetamiprid, nitenpyram, diflubenzuron, and fluorine Acetamiprid, flufenamid, triflumezopyrim, flupyradifurone, spinosad, ethyl spinosad, chlorpyrifos, pyraclostrobin, fipronil, deltamethrin, beta-cyhalothrin, bifenthrin , Fenvalerate, fenvalerate, tefluthrin, beta-cypermethrin, avermectin, avermectin benzoate, pymetrozine, ethiprole, flubenzuron, lice mites Urea, fluoxuron, butyl ether urea, fenflur urea, methoxyfenozide, nitraclopyr, acetazol, fenflufen, bifenazate, pyridaben, triazotin, phentermine Tin, fenformin, indoxacarb, fenflubenzuron, chlorantraniliprole, flubendiamide, bromocyanidin, tetrachloropyramid, insecticidal, insecticidal, fenitrothion, Bacillus thuringiensis , Alkynemite, isocycloseram, tyclopyrazoflor, flupyrimin, oxazosulfyl, benzpyrimoxan, fluazaindolizine, fluxametamide, dicloro mezotiaz, tioxazafen, fluensulfone, pyrifluquinazon, prothioconazole, anisole, tebuconazole, fluconazole, tebuconazole, hexaconazole, Jinggangmycin, tricyclazole, azoxystrobin, oxystrobin, picoxystrobin Any one or a combination of at least two of esters, pyraclostrobin, bifenapram, fluopyramide, prochloraz, flupronil, metalaxyl, or veracol.
12. The pharmaceutical composition containing an m-diamide compound according to any one of claims 1 to 11, wherein a weight ratio of the active ingredient A and the active ingredient B is 200: 1-1: 200.
13. The pharmaceutical composition containing an isodiamide compound according to claim 12, wherein when the active ingredient B in the pharmaceutical composition containing the isodiamide compound is avermectin, the active ingredient A and the active ingredient B The weight ratio is 100: 1-1: 100, preferably 50: 1-1: 10;

    When the active ingredient B in the mesodiamide compound-containing pharmaceutical composition is lambda-cyhalothrin, the weight ratio of the active ingredient A and the active ingredient B is 100: 1-1: 100, preferably 60: 1- 1: 5;

    When the active ingredient B in the mesodiamide compound-containing pharmaceutical composition is ethyl spinosad, the weight ratio of the active ingredient A and the active ingredient B is 100: 1-1: 100, and preferably 20: 1-1. : 20;

    When the active ingredient B in the mesodiamide compound-containing pharmaceutical composition is deltamethrin, the weight ratio of the active ingredient A and the active ingredient B is 50: 1-1: 50, preferably 10: 1-1: 10;

    When the active ingredient B in the mesodiamide compound-containing pharmaceutical composition is fenvalerate, the weight ratio of the active ingredient A and the active ingredient B is 50: 1-1: 50, preferably 10: 1-1: 10;

    When the active ingredient B in the mesodiamide compound-containing pharmaceutical composition is methylaminoavermectin benzoate, the weight ratio of the active ingredient A and the active ingredient B is 100: 1-1: 100, preferably 20: 1-1: 20;

    When the active ingredient B in the mesodiamide compound-containing pharmaceutical composition is flubendicarb, the weight ratio of the active ingredient A and the active ingredient B is 50: 1-1: 50, and preferably 20: 1-1: 20. ;

    When the active ingredient B in the mesodiamide compound-containing pharmaceutical composition is fluoremide, the weight ratio of the active ingredient A and the active ingredient B is 50: 1-1: 50, preferably 20: 1-1: 20 ;

    When the active ingredient B in the mesodiamide compound-containing pharmaceutical composition is pyridaben, the weight ratio of the active ingredient A and the active ingredient B is 50: 1-1: 50, preferably 10: 1-1: 10 ;

    When the active ingredient B in the mesodiamide compound-containing pharmaceutical composition is chlorantraniliprole, the weight ratio of the active ingredient A and the active ingredient B is 100: 1-1: 100, and preferably 20: 1-1. : 20;

    When the active ingredient B in the mesodiamide compound-containing pharmaceutical composition is thiamethoxam, the weight ratio of the active ingredient A and the active ingredient B is 60: 1-1: 50, preferably 20: 1-1: 30 ;

    When the active ingredient B in the pharmaceutical composition containing a metadiamide compound is clothianidin, the weight ratio of the active ingredient A and the active ingredient B is 60: 1-1: 60, preferably 40: 1-1: 40. ;

    When the active ingredient B in the mesodiamide compound-containing pharmaceutical composition is dinotefuran, the weight ratio of the active ingredient A and the active ingredient B is 50: 1-1: 50, and preferably 10: 1-1: 30. ;

    When the active ingredient B in the pharmaceutical composition containing a metadiamide compound is nitenpyram, the weight ratio of the active ingredient A and the active ingredient B is 50: 1-1: 50, preferably 20: 1-1: 20;

    When the active ingredient B in the mesodiamide compound-containing pharmaceutical composition is pymetrozine, the weight ratio of the active ingredient A and the active ingredient B is 100: 1-1: 100, preferably 30: 1-1: 30 ;

    When the active ingredient B in the mesodiamide compound-containing pharmaceutical composition is chlorpyrifos, the weight ratio of the active ingredient A and the active ingredient B is 50: 1-1: 50, preferably 20: 1-1: 30;

    When the active ingredient B in the pharmaceutical composition containing a metadiamide compound is flubendicarb or flubendiamide, the weight ratio of the active ingredient A and the active ingredient B is 100: 1-1: 100, preferably 20 : 1-1: 20;

    When the active ingredient B in the mesodiamide compound-containing pharmaceutical composition is tefluthrin, lufenuron, methoxyfenozide, bismuth, acetimidazole, flufenacil, and fenpyrazole , Bifenthrin, fenpyramine, fenvalerate, butanyl urea, fluazinium, bifenazate, indoxacarb, cyanmethoxam, acetazolonitrile, or fenflufen The weight ratio of A and active ingredient B is 50: 1-1: 50, preferably 20: 1-1: 20;

    When the active ingredient B in the mesodiamide compound-containing pharmaceutical composition is acetamiprid, the weight ratio of the active ingredient A and the active ingredient B is 60: 1-1: 50, and preferably 10: 1-1: 30. ;

    When the active ingredient B in the mesodiamide compound-containing pharmaceutical composition is spinosad, the weight ratio of the active ingredient A and the active ingredient B is 100: 1-1: 100, and preferably 20: 1-1: 30. ;

    When the active ingredient B in the pharmaceutical composition containing a metadiamide compound is triclosan, the weight ratio of the active ingredient A and the active ingredient B is 100: 1-1: 100, preferably 20: 1-1: 20;

    When the active ingredient B in the mesodiamide compound-containing pharmaceutical composition is a combination of fipronil and flupronil, the weight ratio of the active ingredient A and the active ingredient B is 50: 1-1: 50, preferably 20 : 1-1: 20;

    When the active ingredient B in the mesodiamide compound-containing pharmaceutical composition is a combination of tebuconazole and oxystrobin, the weight ratio of the active ingredient A and the active ingredient B is 50: 1-1: 50, preferably 20: 1-1: 20; or

    When the active ingredient B in the mesodiamide compound-containing pharmaceutical composition is a combination of anisoleconazole and veracol, the weight ratio of the active ingredient A and the active ingredient B is 50: 1-1: 50, It is preferably 20: 1-1: 20.
14. The use of a pharmaceutical composition containing an m-diamide compound according to any one of claims 1 to 13 for controlling plant diseases or insect pests in agriculture, forestry, and horticulture.
15. The use of a pharmaceutical composition containing a metadiamide compound according to any one of claims 1 to 13 for seed treatment of plants, crops or flowers.
16. A pharmaceutical preparation, which comprises a pharmaceutical composition containing an m-diamide compound as described above, and an agrochemically acceptable adjuvant and / or carrier;

    Preferably, the carrier includes a filler and / or a solvent;

    Preferably, the agrochemically acceptable adjuvant includes any one or at least one of a dispersant, a wetting agent, an emulsifier, an antifreeze, a thickener, a defoamer, a preservative, a stabilizer, or a colorant. A combination of the two

    Preferably, the dosage form of the pharmaceutical preparation is a solution, a soluble powder, a soluble granule, an emulsifiable concentrate, a wettable powder, an aqueous emulsion, a suspending agent, a dispersible oil suspending agent, a water-dispersible granule, and a microcapsule suspending agent. , Granules, microemulsions, suspension emulsions, microcapsule suspension-suspensions, ultra-low-volume liquids, hot aerosols, film-spreading oils, suspended seed coatings, dry powders for seeds, suspensions for seeds, and seeds for Dissolving powder, seed treatment dispersible powder, seed treatment emulsion or seed treatment liquid;

    Preferably, the dosage form of the pharmaceutical preparation is a solution, a soluble granule, a suspension, an emulsifiable concentrate, a wettable powder, an aqueous emulsion, a water-dispersible granule, a dispersible oil suspension, a microcapsule suspension, and an ultra-low capacity. Liquid, hot aerosol, suspension seed coating or seed treatment dispersible powder.
17. The pharmaceutical preparation according to claim 16, wherein in the pharmaceutical preparation, the weight percentage content of the mesodiamide compound-containing pharmaceutical composition is 0.01-99%.
18. A method for controlling plant pests, comprising: applying an effective dose of a medicinal compound containing a mesodiamide compound according to any one of claims 1 to 5 to a plant disease to be controlled or a growth medium thereof. Or a pharmaceutical preparation according to claim 8 or 9;

    Preferably, the effective dose is 10-1000 g per hectare, preferably 20-500 g per hectare.