WO2020030092A1 - Pharmaceutical composition containing m-diamide compound and application thereof - Google Patents

Abstract

A pharmaceutical composition containing an m-diamide compound and an application thereof. The pharmaceutical composition comprises an active component A and an active component B, wherein the active component A is the m-diamide compound having a structure represented by formula I, and the active component B is a combination of any one or two of other pesticides or bactericides. The composition containing the active component A and the active component B has the unique effects of synergistic interaction, resistant pest control, enlargement of an activity spectrum, virus-transmitting insect control and the like, and can effectively prevent and treat various diseases and insect pests on crops such as rice, corn, wheat, vegetables, fruit trees, flowers, oil materials, sugar materials and the like as well as gardening and forestry.

Description

Pharmaceutical composition containing metadiamide compound and application thereof Technical field

The present application belongs to the technical field of prevention and control of harmful organisms by pharmaceutical compositions, and relates to a pharmaceutical composition containing an isodiamide compound and an application thereof, and in particular, to a composition containing an isodiamide compound and an agricultural antibiotic and an application thereof.

Background technique

In the production of crops such as agriculture and horticulture, the damage caused by pests and diseases 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 desired to develop more efficient insecticide compositions or insecticidal bactericidal 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 pesticides or fungicides;

Wherein Z is selected from hydrogen, fluorine, chlorine, bromine, iodine, cyano, nitro, substituted or unsubstituted 3-10 membered heterocyclic group, 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, 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 is} selected from 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 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;

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 of 0 to 5 (for example, 0, 1, 2, 3, 4 or 5); n represents an integer of 0 to 3 (for example, 0, 1, 2 or 3); W ₁ and W _{2 are} independently an oxygen atom Or 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 amount of a single active ingredient, on the other hand, the control effect is significantly improved, and since the active ingredient A can reach an insecticidal activity of more than 80%, or even 90% -100% at a low dose, the effect is fast. After a few days, the insecticidal activity can be exerted, and a high insecticidal activity can be achieved within 3 days. It can reduce the damage to plants and humans caused by excessive drug concentration, and make less drug residues during application, which is more conducive to environmental protection.

Preferably, the present application provides a pharmaceutical composition containing a compound substituted at the 3-position of m-diamide with an N-cyclopropylmethyl derivative. The pharmaceutical composition includes active ingredient A and active ingredient B. The active ingredient A It is an m-bisamide compound having a structure represented by Formula II, and the active ingredient B includes any one or a combination of other fungicides, insecticides, or acaricides;

In Formula II,

Z is selected from the group consisting of hydrogen, fluorine, chlorine, bromine, iodine, cyano, C ₁ -C ₆ haloalkyl, C ₁ -C ₆ haloalkoxy, C ₁ -C ₆ alkylsulfonyl, or C ₁ -C ₆ haloalkyl Sulfonyl

Y is selected from C ₁ -C ₆ haloalkyl or C ₁ -C ₆ haloalkoxy;

R is selected from hydrogen or methyl.

In this application, an m-bisamide compound having a structure represented by Formula II is further preferred, and it is compounded with active ingredient B as an active ingredient of a pharmaceutical composition. Good results can be achieved at low doses, resulting in less drug residues and more environmental protection.

In the present application, as a preferred technical solution, in Formula I, Z is selected from hydrogen, fluorine, chlorine, bromine, iodine, cyano, trifluoromethoxy, trifluoromethyl, methanesulfonyl, or trifluoromethanesulfonyl. ; Y is selected from trifluoromethyl or trifluoromethoxy; R is selected from hydrogen or methyl.

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

Table 1 Active ingredients A

In Table 1, 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, CF ₃ is a trifluoromethyl group, OCF ₃ is a trifluoromethoxy group, MeS (O) ₂ represents methanesulfonyl, and CF ₃ S (O) ₂ represents trifluoromethanesulfonyl.

In this application, as a particularly preferred technical solution, the m-diamide compound is any one or a combination of at least two selected from the following compounds 1-14:

In this application, the active ingredient B was selected. There are more than 680 known active ingredients of pesticides, and more than 100 commonly used active ingredients. Most of them have different degrees of resistance. Agricultural antibiotics insecticides or fungicides, because they come from biological sources, are environmentally friendly and have low dosages, but they also have drug resistance. In actual production, they have to increase the amount of drugs used. The active ingredient B is selected from any one or a combination of antibiotic bactericides, insecticides, or acaricides in the prior art.

Preferably, the active ingredient B is selected from the group consisting of avermectin, methylaminoavermectin benzoate (formin salt), spinosad, ethyl spinosad, ivermectin, Mibel Any one or a combination of two or more pesticides, fungicides, such as biotin, polyoxin, Jinggangmycin, kasugamycin, and bacteriocin.

As a further preferred technical solution of the present application, the pharmaceutical composition containing the metadiamide compound is a pharmaceutical composition containing the metadiamide compound (active ingredient A) and the active ingredient B described in Table 2 below, but not Limited to the combinations listed in the table.

Table 2

As a preferred technical solution of the present application, the medicinal composition containing an m-bisamide compound is a medicinal composition containing the active ingredient A and the active ingredient B described in Table 1, and the active ingredient B is not limited to the above-mentioned antibiotic-based pharmaceutical products.

The combined effects of the pharmaceutical composition were tested using harmful organisms such as rice cockroach, rice leaf roller, vegetable diamondback moth, vegetable beet armyworm, eggplant thrips, wheat armyworm, wheat scab, rice sheath blight, A synergistic composition was found.

The weight ratio of the active ingredient A and the active ingredient B described herein is 200: 1 to 1: 200, for example, 200: 1, 180: 1, 150: 1, 130: 1, 100: 1, 80: 1, and 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 the metadiamide compound has different preferred weight ratios according to the difference between the active ingredient A and the active ingredient B. As a preferred technical solution of the present application, when the active ingredient is When A and active ingredient B are selected from the components described 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: 50
Compound of formula I: ethyl spinosad	100: 1 ～ 1: 100	50: 1 ～ 1: 50
Compound of Formula I: Methylavermectin Benzoate	100: 1 ～ 1: 100	80: 1 ～ 1: 80
Compound of Formula I: Spinosad	100: 1 ～ 1: 100	60: 1 ～ 1: 60
Compound of Formula I: Polyclonal	100: 1 ～ 1: 100	20: 1 ～ 1: 20
Compound of formula I: Jinggangmycin	100: 1 ～ 1: 100	50: 1 ～ 1: 50

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.

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.

On the other hand, the present application provides the application of the pharmaceutical composition or pharmaceutical preparation containing the metadiamide compound as described above in the prevention, control of plant diseases or insect pests in agriculture, forestry, and horticulture.

The medicinal composition or medicinal preparation containing the metadiamide compound described in the present application is suitable for controlling various agricultural, forestry, horticultural pests and sanitary pests that harm rice, corn, wheat, potato, fruit trees, vegetables, other crops and flowers, and Disease.

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 the pharmaceutical composition.

In the present application, the pests include lepidoptera, coleoptera, hemiptera, tarptera, diptera, orthoptera, homoptera, isoptera, hymenoptera, and spider mite, said Diseases include diseases caused by semi-known bacteria, ascomycetes, basidiomycetes, and the like.

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 diseases include, but are not limited to, wheat scab, rice sheath blight, rice blast and the like.

In the present application, the method of using the pharmaceutical composition or pharmaceutical preparation is spraying, soil treatment, seed treatment, flight prevention, and the like.

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 method for controlling plant diseases and insect pests, which method is: applying an effective dose of the above-mentioned pharmaceutical composition containing metadiamide compounds to a plant disease to be controlled or a growth medium thereof Or pharmaceutical preparations.

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 (especially the compound of the general formula II) 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 pharmaceutical composition of the present application has the following advantages in use:

(1) The composition 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 alone, and the control effect is significantly improved; due to the significant resistance of active ingredient A to resistant pests The activity also solves the prevention and control of important crop diseases and insect pests such as diploid pupae, diamondback moth, thrips and other important crops.

(2) Because of the different action mechanisms of active ingredient A and active ingredient B, the drug resistance can be delayed after compounding, which is an effective resistance risk management tool and extends the life cycle of the drug.

(3) The active ingredient A described in this application is compounded with the active ingredient B of different control objects, which expands the spectrum of control and saves labor costs of medication, and can be applied to vegetables, fruit trees, flowers, cereals, oil, sugar, etc. Crops, horticulture, forestry, health and various diseases and insect pests. In addition, it has extremely high activity against newly emerged Spodoptera frugiperda, which can be used for emergency prevention and control, which is conducive to maintaining environmental ecological security and social stability.

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

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

To the reaction flask were sequentially added methyl 2-fluoro-3-aminobenzoate (20 g, 118.23 mmol), bromomethylcyclopropane (20.75 g, 153.70 mmol), potassium carbonate (21.24 g, 153.70 mmol), N, N-dimethylformamide (200 mL) was stirred under reflux for 16 h. When the reaction was monitored by TLC, 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 a pale yellow liquid product 2-fluoro- [3- (cyclopropylmethyl) amino [methyl benzoate (13 g, yield 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) benzamido] 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 concentrated under reduced pressure to obtain a colorless solution product, 2-fluoro-3- [N- (cyclopropylmethyl) benzamide] Benzoic acid (12.00 g, yield 93.82%), after standing overnight, turned into a white solid.

(4) N- [2-Bromo-4- (1,1,1,2,3,3,3-heptafluoroprop-2-yl) -6- (trifluoromethyl) phenyl] -3- Synthesis of [N- (cyclopropylmethyl) benzamide] -2-fluorobenzamide

To the reaction flask were added 2-fluoro-3- (N- (cyclopropylmethyl) benzamido) benzoic acid (0.40 g, 1.28 mmol), toluene (6 mL), and dichlorosulfoxide (0.75 g, 6.40) in this order. mmol), stirred at 140 ° C. for 2 h, and concentrated under reduced pressure. The concentrated residue was dissolved in tetrahydrofuran (3 mL) until use.

2-Bromo-6-trifluoromethyl-4-heptafluoroisopropylaniline (0.52 g, 1.28 mmol) was dissolved in tetrahydrofuran (4 mL), and lithium diisopropylaminoamide (0.77 mL) was added dropwise at -70 ° C. , 1.54 mmol), 5 minutes later, a tetrafluorofuran solution of 2-fluoro-3- [N- (cyclopropylmethyl) benzamido] benzoyl chloride synthesized in one step was added dropwise, stirred at -70 ° C for 30 minutes, and raised to Stirring was continued for 30 min at room temperature. 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 N- [2-bromo-4- (1,1,1,2,3,3,3-heptafluoroprop-2-yl) -6- (tri Fluoromethyl) phenyl] -3- [N- (cyclopropylmethyl) -benzamido] -2-fluorobenzamide (0.25 g, yield 27.84%).

¹ H NMR of compound 1 (400 MHz, CDCl ₃ -d), δ [ppm]: 8.15 (d, J = 2.1 Hz, 1 H), 8.03 (br s, 2 H), 7.92 (d, J = 2.1 Hz, 1 H ), 7.55 (br s, 1H), 7.35-7.21 (m, 5H), 3.84 (d, J = 93.6 Hz, 2H), 1.14 (br s, 1H), 0.59-0.40 (m, 2H), 0.20 ( d, J = 42.2Hz, 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. 3)

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 3 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 (cyclopropylmethyl) -4-cyanobenzamide] -2-fluorobenzamide (Compound No. 4):

(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 give 2-fluoro-3- [N- (cyclopropylmethyl) -4-cyanobenzamide] 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) extraction, the organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, and then concentrated under reduced pressure to obtain 2-fluoro-3- [N- (cyclopropylmethyl) -4-cyanobenzamide ] Benzoic acid (1.30 g, yield 96.79%), white solid.

(3) N- [2-Bromo-4- (1,1,1,2,3,3,3-heptafluoroprop-2-yl) -6- (trifluoromethyl) phenyl] -3- Synthesis of [N- (cyclopropylmethyl) -4-cyanobenzamide] -2-fluorobenzamide:

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 of compound 4 (400 MHz, CDCl ₃ -d), δ [ppm]: 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 4

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. 7):

(1) Add 2-fluoro-3- [N- (cyclopropylmethyl) -4-trifluoromethylbenzamide] 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%).

¹ H NMR (400MHz, CDCl ₃ -d) δ [ppm] of Compound 7: 8.21-7.79 (m, 4H), 7.66-7.28 (m, 5H), 3.85 (d, J = 104.7Hz, 2H), 1.12 (br s, 1H), 0.51 (br s, 2H), 0.20 (d, J = 42.7 Hz, 1H).

Synthesis Example 5

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. 8) 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 8: 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 6

N- [2-Bromo-4- (1,1,1,2,3,3,3-heptafluoroprop-2-yl) -6- (trifluoromethyl) phenyl] -3- [N- (Cyclopropylmethyl) -4-chlorobenzamide] -2-fluorobenzamide (Compound No. 10) was prepared as follows:

(1) Add 2-fluoro-3- [N- (cyclopropylmethyl) -4-chlorobenzamide] benzoic acid (0.60 g, 1.76 mmol), toluene (6 mL), 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%).

¹ H NMR (400MHz, CDCl ₃ -d) δ [ppm] of Compound 10: 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 (br s, 1H), 0.49 (br s, 2H), 0.17 (d, J = 32.1 Hz, 2H).

Synthesis Example 7

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. 2) 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 triacetoxyborohydride (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 methyl 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.

Dissolve methyl 3- [N- (1-cyclopropyl) ethyl) amino] -2-fluorobenzoate (2.50 g, 10.54 mmol) in tetrahydrofuran (15 mL), and add triethylamine (1.60 g, 15.80 in this order). mmol) and the tetrahydrofuran solution of the acid chloride prepared in the previous step, and the reaction was 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. Ester (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.

¹ H NMR (400MHz, CDCl ₃ -d), δ [ppm] of compound 2: 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 (br s, 2H), 1.51 (br s, 1H), 0.89-0.40 (m , 5H).

Except for the compounds described above, some of the compounds in Table 1 were prepared by a similar method as in Synthesis Examples 1-7, and the NMR data of some of the compounds synthesized with reference to Synthesis Examples 1-7 are given in Table 4 below.

Table 4

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: 24% compound 6. Jinggangmycin solution

The composition of the 24% compound 6 · jinggangmycin solution is shown in Table 5 below:

table 5

name	Hundred percent (W / W,%)	Note
Compound 6	12	Active ingredient A
Jinggangmycin	12	Active ingredient B
Propylene glycol methyl ether	10	Cosolvent
Fatty alcohol polyoxyethylene ether	6	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 6, Jinggangmycin, heat to 30-40 ° C and stir for 2 hours. Finally add fat Alcohol polyoxyethylene ether, dissolved uniformly, and filtered to obtain a solution of 24% compound 6. Jinggangmycin.

Formulation Example 2: 10% Compound 8 · Avermectin EC

The composition of 10% Compound 8 · Avermectin EC is shown in Table 6 below:

Table 6

name	Hundred percent (W / W,%)	Note
Compound 8	5	Active ingredient A
Avermectin	5	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-neck flask, add xylene, add compound 8, avermectin, calcium dodecylbenzenesulfonate, and castor oil polyoxyethylene ether. Stir at 50 ° C for 1.5 hours and filter to obtain 10% Compound 8. Avermectin EC.

Formulation Example 3: 30% Compound 4 · Polyoxin Wettable Powder

The 30% compound 4 · polyoxin wettable powder is shown in Table 7:

Table 7

name	Hundred percent (W / W,%)	Note
Compound 4	25	Active ingredient A
Polymycin	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 mixing compound 4, polyoxin, sodium lauryl sulfate, sodium lignin sulfonate, and kaolin, uniformly pulverize to an average particle size of 10 microns with a jet mill That is, 30% of compound 4 · polyoxin wettable powder was obtained.

Formulation Example 4: 25% Compound 2 · Jinggangmycin Water Emulsion

25% Compound 2 · Jinggangmycin water emulsion is shown in Table 8:

Table 8

Preparation method: Calculate the amount of each material according to the formula, dissolve Compound 2, Jinggangmycin, castor oil polyoxyethylene ether, and xylene uniformly at 40-50 ° C as Phase A; deionized water, propylene glycol, and tribenzene Vinylphenol polyoxyethylene ether phosphate is stirred and dissolved uniformly as Phase B; under high shear, add Phase A to Phase B slowly, cut to an average particle size of 1.5 microns, and add 0.1 parts of Carson 10 parts of 1% yellow The original gum solution was stirred for 30 minutes to obtain 25% Compound 2 · Jinggangmycin water emulsion.

Formulation example 5: 15% compound 8. ethyl spinosad suspension

15% Compound 8 · ethyl spinosad suspension agent is shown in Table 9:

Table 9

name	Hundred percent (W / W,%)	Note
Compound 8	10	Active ingredient A
Ethyl spinosad	5	Active ingredient B
Fatty alcohol polyoxyethylene ether	1.5	moisturizer
Tristyryl phenol polyoxyethylene ether phosphate	2	Dispersant
Sodium lignosulfonate	3	Dispersant
Propylene glycol	4	antifreeze
1% xanthan gum solution	10	Thickener
Casson	0.1	preservative
Polydimethylsiloxane	0.2	Silicone defoamer
Deionized water	Make up 100	Carrier

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, add ethyl poly The bactericidin and compound 8 were sheared uniformly, and then ground to an average particle diameter of 2 microns by a sand mill, and 10 parts of a 1% xanthan gum solution was added and stirred for 30 minutes to obtain 15% of a compound 8 · ethyl spinosad suspension.

Formulation Example 6: 25% Compound 3 · Avermectin Water Dispersible Granules

25% Compound 3 · Avermectin water-dispersed granules are shown in Table 10:

Table 10

name	Hundred percent (W / W,%)	Note
Compound 3	20	Active ingredient A
Avermectin	5	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 3, avermectin, sodium lauryl sulfate, sodium lignin sulfonate, sodium naphthalene formaldehyde polymer sulfonate, ammonium sulfate, corn starch, and kaolin. , Pulverized by an air jet mill to an average particle size of 10 to 15 microns, kneaded by adding 17% of the powder amount, and then granulated by rotary extrusion, dried at 50 ° C for 3 hours, and sieved to obtain 25% compound 3 · Avermectin water-dispersible granules.

Formulation Example 7: 5% Compound 1 · Aminoavermectin benzoate dispersible oil suspension

The 5% compound 1 · methylaminoavermectin benzoate dispersible oil suspension is shown in Table 11:

Table 11

name	Hundred percent (W / W,%)	Note
Compound 1	3	Active ingredient A
Methylavermectin benzoate	2	Active ingredient B
Fatty acid polyoxyethylene ether	10	Emulsifier
Styrylphenol polyoxyethylene ether	3	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, add compound 1, methylamino Avermectin benzoate, The organic bentonite and fumed silica were sheared uniformly, and then ground to an average particle diameter of 4 micrometers by a sand mill to obtain a 5% compound 1 · methylaminoavermectin benzoate dispersible oil suspension agent.

Formulation Example 8: 35% Compound 10 · Aminoavermectin Benzoate Microcapsule Suspension

The 35% compound 10 · methylaminoavermectin benzoate microcapsule suspension is shown in Table 12:

Table 12

name	Hundred percent (W / W,%)	Note
Compound 10	15	Active ingredient
Methylavermectin benzoate	20	Active ingredient
Polyaryl polymethylene polyisocyanate	2	Capsule
Tristyryl phenol polyoxyethylene ether phosphate	2	Dispersant
EO / PO polymer (D-800)	3	Emulsifier
Propylene glycol	4	antifreeze
Xylene	20	Solvent
Hexamethylene diamine	0.5	Capsule
1% xanthan gum solution	10	Thickener
Casson	0.1	preservative
Polydimethylsiloxane	0.2	Defoamer

Deionized water

Make up 100

Carrier

Preparation method: Calculate the amount of each material according to the formula. Dissolve compound 10, methylamino avermectin benzoate, polyaryl polymethylene polyisocyanate, and xylene uniformly at 40-50 degrees as Phase A. ; Another take deionized water, D-800, propylene glycol, dissolve uniformly, as phase B; under high shear, slowly add phase A to phase B, cut to an average particle size of 2 to 3 microns, and then add the material to In a three-necked flask, hexamethylene diamine was added, and the reaction was stirred at 50 to 60 ° C for 10 hours. Tristyrenol phenol polyoxyethylene ether phosphate, kasson, an antifoaming agent, and a 1% xanthan gum solution were stirred for 1 hour. 35% Compound 10 · Aminoavermectin Benzoate Microcapsule Suspension was obtained.

Biometric Example

The following examples are used to illustrate the partial implementation of the technical solution of the present application, and the present application is not limited to the following examples.

Bioassay Example 1: Active ingredient A has significant activity against various pests

Targets: Plutella xylostella 3rd instar larvae, armyworm 3rd instar larvae, diploid pupae 3rd instar larvae, all reared indoors.

Methods: Plutella xylostella + leaf soaking feeding method, slimeworm + leaf soaking feeding method, diploid pupae + rice stem soaking method.

Plutella xylostella + leaf soaking feeding method. With reference to NY / 1154.14-2008, the main operation description is as follows: immerse the clean bract leaf dish in the medicinal solution for 10s, dry it and place it in petri dishes, 4 dishes per dish, put filter paper 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 and live insects of Plutella xylostella was investigated 3 days after the administration, and the mortality was calculated.

Feeding on slime + dipping leaf. With reference to NY / 1154.14-2008, the main operation description is as follows: immerse the clean corn leaf section in the medicinal solution for 10s, dry it and place it in petri dishes, 4 pieces per dish, put filter paper in the petri dish to moisturize. Ten dishes of slimeworms were received in each dish, and 3 replicates were performed. 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.

Erhuan + rice stalk dipping method. With reference to NY / T1154.11-2008, the main operation is as follows: immerse the cleaned rice stalks in the medicinal solution for 10s, remove them, place them in a cool place to dry, put them into finger tubes, and insert 10 third-instar larvae. Each treatment was repeated 3 times. The mouth of the tube was sealed with a black cotton cloth. The rubber band was tied tightly and placed in a light incubator at 28 ° C in the dark. The number of dead worms in P. chinensis was investigated 3 days after the treatment, and the mortality of each treatment was calculated.

The results are shown in Table 13. From the results, it can be seen that compounds 1-14 all have extremely significant insecticidal activity.

Table 13

Bioassay Example 2: The composition of active ingredient A is a compound of formula II 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 14. From the results, it can be seen that when the active ingredient A is compound 4, compound 6, compound 7, compound 8, compound 9, compound 10, compound 11, compound 12, compound 13, Excellent activity; when the active ingredient B is avermectin, methylamino avermectin benzoate, and ethyl spinosad, it has excellent activity on dioxin; when A and B are combined, the combined effect is increased Efficiency and significant efficiency gains.

Table 14 Insecticidal activity of the test reagents against pupae

Bioassay Example 3 : Active ingredient A is a compound of formula II and active ingredient B is avermectin, ivermectin, spinosad, etc., and its activity is tested against Plutella xylostella

Target: Plutella xylostella 3rd instar larvae, reared indoors.

Methods: The method was described in the same way as in Example 1. The evaluation method was the same as in Example 2.

The results are shown in Table 15. It can be seen from the results that when the active ingredient A is Compound 1, it has excellent activity against Plutella xylostella; when the active ingredient B is Avermectin, Ivermectin, and Spinosad, it is Has excellent activity; when A and B are combined, the combined effect appears to be synergistic or significant synergistic.

Table 15 Insecticide activity against Plutella xylostella

Test agent or combination name	Dose mg / L	3d mortality%	Theoretical mortality%	Synergy effect	Joint mode of action
Compound 1	0.01	36.67	/	/	/
Avermectin	0.06	70	/	/	/
Ivermectin	0.4	75	/	/	/
Spinosad	0.06	60	/	/	/
Compound 1 + Avermectin	0.01 + 0.06	100	68.35	31.65	Significant synergy
Compound 1 + Ivermectin	0.01 + 0.4	100	84.17	15.83	Synergy
Compound 1+ spinosad	0.01 + 0.06	100	74.67	25.33	Significant synergy

Bioassay Example 4: The composition of active ingredient A is a compound of formula II and active ingredient and B is methylaminoavermectin benzoate, ivermectin, mibelin

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 2.

The results are shown in Table 16. From the results, it can be seen that when the active ingredient A is compound 3 and compound 5, it has excellent activity against the armyworm; the active ingredient B is methylaminoavermectin benzoate, ivermectin When mibemycin is used, it has excellent activity against the armyworm. When A and B are combined, the combined effect is synergistic or significantly synergistic.

Table 16 Insecticide activity against testworms in laboratory

Bioassay Example 5: Activity test of a combination of compound 8 and avermectin on pyrene disulfide

Insect source: 3rd instar larvae of pupae, indoor breeding.

Method: Rice stalk immersion method, the operation description is described in Example 1. The evaluation method is referred to NY / T1154.7-2006, and the co-toxicity coefficient is used for evaluation.

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 actual virulence index;

S—LC _{50 of} standard medicine, unit is milligram per liter (mg / L);

M—LC _{50 of the} test agent in milligrams per liter (mg / L).

TTI = A × P _A + B × P _B ······································ ····························(2)

In the formula: TTI-mixture theoretical virulence index;

A—A actual virulence index of medicament;

P _A —A percentage content of the agent in the mixture, the unit is percentage (%);

B—B actual virulence index of medicament;

The percentage of P _B —B agent in the mixture, the unit is percentage (%).

In the formula: CTC—co-toxicity coefficient; ATI—mixture actual 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.

The results are shown in Table 17. From the results, it can be seen that compound 8 and avermectin both have good activity on Diosmium Diosmium; compound 8 and avermectin are mixed in a ratio of 100: 1 to 1: 100. The co-toxicity coefficient is 100.28 ～ 157.02, which shows an additive or synergistic effect; when the compound 8 and avermectin ratio is 100: 1 to 1: 5, the co-toxic coefficient is greater than 120, which shows a synergistic effect.

Table 17 Co-toxicity coefficients of the compound 8 and avermectin on dioxin (3d after treatment)

Bioassay Example 6: Activity Test of a Composition of Compound 3 and Methyl Avermectin Benzoate on Spodoptera exigua

Insect source: 3rd instar larvae of Spodoptera exigua, reared indoors.

Methods: Soaked leaf dish feeding method. The operation description is as follows: immerse the clean bract leaf dish in the medicinal solution for 10s, dry it, and place it in a 24-well plate. Each well receives one test of beet armyworm, and each handles 24. It was placed in a light incubator at a temperature of 25 ° C under 14hL: 10hD and cultured. The number of dead and alive insects was investigated 3 days after the administration, and the mortality was calculated.

Statistical evaluation contemporaneous test example 5

The results are shown in Table 18. From the results, it can be seen that both compound 3 and methylamino avermectin benzoate have good activity against Spodoptera exigua; compound 3 and methylamino avermectin benzoate are complex. When the ratio is 160: 1 to 1: 160, the co-toxicity coefficient is 101.05 to 277.48, which shows an additive or synergistic effect. When the ratio is 40: 1 to 1:80, the co-toxicity coefficient is greater than 120, which shows an increase. Effect.

Table 18 Co-toxicity coefficients of compound 3 and methylaminoavermectin benzoate on Spodoptera exigua (3d after treatment)

Bioassay Example 7: Activity Test of a Compound 1 and Spinosad Composition on Plutella xylostella

Insect source: Plutella xylostella 3rd instar larvae, reared indoors.

Methods: The method of feeding by leaf immersion dish was described in the same test example 1 and the statistical evaluation of the same test example 5 was performed.

The results are shown in Table 19. From the results, it can be seen that compound 1 and spinosad have good activity against Plutella xylostella; the co-toxicity coefficient of compound 1 and spinosad is compounded at a ratio of 200: 1 to 1: 200. It is 94.12 ～ 212.13, showing an additive or synergistic effect; when the ratio is 120: 1 to 1:60, the co-toxicity coefficients are all greater than 120, showing a synergistic effect.

Table 19 Co-toxicity coefficients of the compound 1 and spinosad composition against Plutella xylostella

Bioassay Example 8: Test of the activity of the composition of compound 9 and ethyl spinosad against Plutella xylostella

Insect source: Plutella xylostella 3rd instar larvae, reared indoors.

Method: Leaf soaking method. Operation description Contemporaneous test embodiment 1, statistical evaluation of concomitant test embodiment 5.

The results are shown in Table 20. From the results, it can be seen that compound 9 and ethyl spinosad have good activity against Plutella xylostella; compound 9 and ethyl spinosad are mixed at a ratio of 100: 1 to 1: 100. The co-toxicity coefficient is 102.27 to 314.59, which shows an additive or synergistic effect; when the ratio is 50: 1 to 1:50, the co-toxicity coefficient is greater than 120, which shows a synergistic effect.

Table 20 Co-toxicity coefficients of the compound 9 and ethyl spinosad against Plutella xylostella (3d after treatment)

Bioassay Example 9: Activity test of a compound 12 and avermectin on Plutella xylostella

Insect source: Plutella xylostella 3rd instar larvae, reared indoors.

Method: Leaf soaking method. Operation description Contemporaneous test embodiment 1, statistical evaluation of concomitant test embodiment 5.

The results are shown in Table 21. From the results, it can be seen that compound 12 and avermectin have good activity against Plutella xylostella; compound 12 and avermectin are compounded at a total ratio of 100: 1 to 1: 100. The toxicity coefficient is 91.55 ～ 241.44, which shows an additive or synergistic effect. When the ratio is 50: 1 ～ 1: 50, the co-toxicity coefficients are all greater than 120, showing a synergistic effect.

Table 21 Co-toxicity coefficients of compound 12 and avermectin on Plutella xylostella

Bioassay Example 10: 25% compound 10 · polyoxin wettable powder (compound 10 mass concentration of 10%, polyoxin mass concentration of 15%) Field control of wheat scab, and armyworm control

Crops and metallurgical objects: wheat, early flowering period, scab, slime

Method: Foliar spray method, water consumption 45L / 667m ²

The results are shown in Table 22. From the results, it can be seen that the 25% compound 10 · polymycin WP has excellent control effects on wheat scab and armyworm, and has achieved the purpose of expanding the spectrum of activity and saving the number of medications.

Table 22 Statistics of the investigation results of the tested pesticides against wheat scab and armyworm

Bioassay Example 11: 24% Compound 8 · Jinggangmycin solution (Compound 8 mass concentration is 12%, Jinggangmycin mass concentration is 12%) Field control of rice leaf curl, and rice sheath blight

Crops and targets: rice, leaf roller, rice sheath blight

Method: Foliar spray method, water consumption 45L / 667m ²

The results are shown in Table 23. From the results, it can be seen that the 24% compound 8 · Jinggangmycin solution has excellent control effects on rice leaf curl and rice sheath blight, and has expanded the spectrum of activity and saved medicine. The purpose of the number of times.

Table 23 Statistics of the investigation results of the tested pesticides against rice leaf curl and rice sheath blight

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 (15)

1. A pharmaceutical composition containing a metadiamide compound, comprising 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 includes other pesticides Or any one or a combination of two fungicides;

   

   In Formula I, Z is selected from hydrogen, fluorine, chlorine, bromine, iodine, cyano, nitro, substituted or unsubstituted 3-10 membered heterocyclyl, 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 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 halocycloalkyl 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 alkane Group, C ₁ -C ₆ haloalkyl, C ₃ -C ₈ cycloalkyl or C ₃ -C ₈ halocycloalkyl; m represents an integer of 0 to 5; n represents an integer of 0 to 3; W ₁ and W _{2 is} independently an oxygen atom or a sulfur atom.
2. The pharmaceutical composition containing a metadiamide compound according to claim 1, wherein the active ingredient A is a metadiamide compound having a structure represented by Formula II:

   

   In Formula II,

   Z is selected from the group consisting of hydrogen, fluorine, chlorine, bromine, iodine, cyano, C ₁ -C ₆ haloalkyl, C ₁ -C ₆ haloalkoxy, C ₁ -C ₆ alkylsulfonyl, or C ₁ -C ₆ haloalkyl Sulfonyl

   Y is selected from C ₁ -C ₆ haloalkyl or C ₁ -C ₆ haloalkoxy;

   R is selected from hydrogen or methyl.
3. The pharmaceutical composition containing an m-bisamide compound according to claim 2, wherein in Formula II,

   Z is selected from hydrogen, fluorine, chlorine, bromine, iodine, cyano, trifluoromethoxy, trifluoromethyl, methanesulfonyl or trifluoromethanesulfonyl;

   Y is selected from trifluoromethyl or trifluoromethoxy;

   R is selected from hydrogen or methyl.
4. The pharmaceutical composition containing an m-bisamide compound according to any one of claims 1 to 3, wherein the m-bisamide compound is any one or at least two selected from the following compounds 1-14 combination:

   
5. The pharmaceutical composition containing a metadiamide compound according to any one of claims 1 to 4, wherein the active ingredient B is any one or two of an antibiotic insecticide, a bactericide or an acaricide. Combination.
6. The medicinal composition containing a metadiamide compound according to claim 5, wherein the active ingredient B is selected from the group consisting of avermectin, methylamino avermectin benzoate, spinosyn, and ethylpoly Any one or a combination of bactericidin, ivermectin, mibelmycin, polyoxin, Jinggangmycin, kasugamycin, or nystatin.
7. The pharmaceutical composition containing an m-bisamide compound according to any one of claims 1-6, wherein a weight ratio of the active ingredient A and the active ingredient B is 200: 1-1: 200.
8. The pharmaceutical composition containing an isodiamide compound according to claim 7, 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: 50;

   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 80: 1 ～ 1: 80;

   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 60: 1 to 1:60. ;

   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 50: 1-1. : 50;

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

   When the active ingredient B in the mesodiamide compound-containing pharmaceutical composition is Jinggangmycin, the weight ratio of the active ingredient A and the active ingredient B is 100: 1-1: 100, and preferably 50: 1-1: 50. .
9. A pharmaceutical preparation comprising the pharmaceutical composition containing an m-diamide compound according to any one of claims 1 to 8 and an agrochemically acceptable adjuvant and / or a carrier.
10. The pharmaceutical formulation according to claim 9, wherein the agrochemically acceptable adjuvant includes a dispersant, a wetting agent, an emulsifier, an antifreeze, a thickener, a defoamer, a preservative, a stabilizer, or a dye Any one or a combination of at least two of the agents; and

    The carrier includes a filler and / or a solvent.
11. The pharmaceutical preparation according to claim 9, wherein 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, water Dispersing granules, microcapsule suspensions, granules, microemulsions, suspension emulsions, microcapsule suspension-suspensions, ultra-low-volume liquids, thermal sprays, film spreading oils, suspension seed coatings, seed treatment dry powders, Seed treatment suspending agent, seed treatment soluble 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.
12. The pharmaceutical preparation according to claim 9, wherein in the pharmaceutical preparation, the weight percentage content of the mesodiamide compound-containing pharmaceutical composition is 0.01-99%, preferably 0.5-95%.
13. Use of the pharmaceutical composition according to any one of claims 1 to 8 or the pharmaceutical preparation according to any one of claims 9 to 12 for controlling plant diseases or insect pests in agriculture, forestry, and horticulture;

    Preferably, spraying, watering or seed treatment is used during application.
14. A method for controlling plant diseases and insect pests, which is: applying an effective dose of the medicinal amide compound-containing pharmaceutical composition according to any one of claims 1 to 8 to a plant disease or pest that needs to be controlled or a growth medium thereof. Or a pharmaceutical preparation according to any one of claims 9-12.
15. The method according to claim 14, wherein the effective dose is 10-1000 g per hectare, preferably 20-500 g per hectare.