An amide compound having a sterilization and insecticidal effect and use thereof

Abstract

The application discloses an amide compound with sterilization and insecticidal effects and application thereof, and the amide compound has a structure shown in formula I, wherein R1 is defined in the description. The compound has excellent insecticidal and sterilization effects, and has wide application prospects in preventing and treating diseases and insect pests of crops.

Description

Technical Field

[0001] This invention belongs to the field of pesticide chemistry, specifically relating to an amide compound with both fungicidal and insecticidal effects. This invention also relates to compositions comprising the compounds of this invention and their application in agricultural prevention of plant diseases and pests. Technical Background

[0002] Plant parasitic nematodes are important plant pathogens, characterized by their concealment, multi-hostability, persistence, and ease of transmission. Their populations grow rapidly and are difficult to control, severely impacting the yield and economic benefits of grains, vegetables, and cash crops in my country. Their main host crops include soybeans, potatoes, cotton, corn, tomatoes, carrots, and sugar beets. Currently, nematode damage is becoming increasingly serious, posing a significant threat to crop production. Globally, nematode damage causes crop yield reductions of up to 14% annually, resulting in economic losses of US$80-100 billion. In my country, nematode infestations cause crop yield reductions as high as 12% annually, with soybean yield losses due to nematodes alone ranging from 5% to 80% annually. Parasitic nematodes damage plant roots, and after infection, they easily trigger fungal infections, exacerbating bacterial, fungal, and viral damage, thus impairing plant growth and reducing crop yield and quality.

[0003] Plant diseases are also a significant factor in reduced plant yields. Amide compounds are used for sterilization primarily by inhibiting mitochondrial respiration by blocking electron transfer in succinate dehydrogenase in the respiratory chain, and are characterized by a broad-spectrum bactericidal effect and good bactericidal efficacy.

[0004] The applicant previously reported a class of novel amide compounds in patent CN116947749A, with the following general formula:

[0005]

[0006] These compounds have good insecticidal effects.

[0007] CN106242998A reports a class of diamide compounds with insecticidal activity, which have the following structure:

[0008]

[0009] CN104024225A discloses a class of compounds that kill insecticidal organisms, having the following structure.

[0010]

[0011] Long-term use of pesticides can lead to resistance and reduce their effectiveness. Therefore, the search for superior active compounds has been a hot topic and trend in this field of research. Summary of the Invention

[0012] This invention provides an amide compound with excellent bactericidal and insecticidal effects, its preparation method, and its application.

[0013] To achieve the above objectives, a first aspect of the present invention provides an amide compound of formula I, its isomers, or salts thereof.

[0014] ,

[0015] I

[0016] R1 is selected from halogens or halogenated C1-C6 alkyl groups.

[0017] A second aspect of the present invention provides a composition comprising an adjuvant and a compound and / or a salt thereof described in the first aspect of the present invention; wherein the adjuvant is selected from at least one of surfactants, solid diluents and liquid diluents.

[0018] A third aspect of the present invention provides the use of the compounds and / or salts thereof described in the first aspect of the present invention and the compositions described in the second aspect of the present invention in the prevention and control of plant fungal and insect pests.

[0019] Beneficial effects of the invention

[0020] The compound of this invention has both insecticidal and bactericidal effects, and has broad application prospects. Detailed Implementation

[0021] To make the objectives, technical solutions, and advantages of the embodiments of the present invention clearer, the technical solutions in the embodiments of the present invention will be clearly and completely described below. Obviously, the described embodiments are only some embodiments of the present invention, not all embodiments. Based on the embodiments of the present invention, all other embodiments obtained by those skilled in the art without creative effort are within the scope of protection of the present invention. Unless otherwise expressly stated, throughout the specification and claims, the term "comprising" or its variations such as "including" or "comprising of," etc., will be understood to include the stated components or steps, without excluding the presence of other substances or steps.

[0022] Furthermore, to better illustrate the present invention, numerous specific details are provided in the following detailed embodiments.

[0023] Those skilled in the art will understand that the present invention can be practiced even without certain specific details. In some embodiments, materials, methods, and means well known to those skilled in the art are not described in detail in order to highlight the spirit of the invention.

[0024] When the compounds of the present invention can exist in tautomer form, the compounds described above and below should be understood, where applicable, to also include the corresponding tautomer forms, even if such tautomer forms are not explicitly mentioned in each case.

[0025] If the compound of Formula I described in this invention has one or more chiral centers and is therefore present as an enantiomer or diastereomer, then the pure enantiomer, the racemic version, or the diastereomer may be used in the compositions of this invention.

[0026] Any asymmetric atom (e.g., carbon, etc.) in the compounds disclosed in this invention can exist in racemic or enantiomerically enriched forms, such as (R)-, (S)-, or (R,S)- configurations.

[0027] If the compounds of Formula I described in this invention have functional groups that can be ionized, they can also be used as agricultural salts or mixtures thereof. The salts described in this invention can be inorganic salts such as hydrochlorides, hydrobroms, sulfates, nitrates, and phosphates, but are not limited thereto. They can also be organic acid salts such as formates, acetates, oxalates, fumarates, methanesulfonates, and benzenesulfonates, but are not limited thereto.

[0028] As used herein, the term "alkyl" (and in other groups containing alkyl, such as the alkyl portion of a haloalkyl, the alkyl structural portion of an alkylsulfinyl, an alkylsulfonyl, or a haloalkylsulfonyl) in each case means a straight-chain or branched alkyl group generally having 1-20 carbon atoms, often 1-10 carbon atoms, preferably 1-6 carbon atoms, and especially 1-4 carbon atoms. Examples of C1-C4 alkyl groups are methyl, ethyl, n-propyl, isopropyl, n-butyl, 1-methylpropyl (sec-butyl), 2-methylpropyl (isobutyl), and 1,1-dimethylethyl (tert-butyl). Examples of C1-C6 alkyl groups, in addition to those mentioned for C1-C4 alkyl groups, include n-pentyl, 1-methylbutyl, 2-methylbutyl, 3-methylbutyl, 2,2-dimethylpropyl, 1-ethylpropyl, 1,1-dimethylpropyl, 1,2-dimethylpropyl, hexyl, 1-methylpentyl, 2-methylpentyl, 3-methylpentyl, 4-methylpentyl, 1,1-dimethylbutyl, 1,2-dimethylbutyl, 1,3-dimethylbutyl, 2,2-dimethylbutyl, 2,3-dimethylbutyl, 3,3-dimethylbutyl, 1-ethylbutyl, 2-ethylbutyl, 1,1,2-trimethylpropyl, 1,2,2-trimethylpropyl, 1-ethyl-1-methylpropyl, or 1-ethyl-2-methylpropyl.

[0029] In this invention, the halogen is typically fluorine, chlorine, bromine, or iodine, preferably fluorine, bromine, or chlorine. Correspondingly, this also applies to halogens combined with other structures, such as alkyl halogens. Alkyl halogens preferably have a chain length of 1 to 6 carbon atoms, more preferably a chain length of 1 to 4 carbon atoms. Examples of alkyl halogens include fluoromethyl, difluoromethyl, trifluoromethyl, chloromethyl, dichloromethyl, trichloromethyl, 2,2,2-trifluoroethyl, 2-fluoroethyl, 2-chloroethyl, pentafluoroethyl, 1,1-difluoro-2,2,2-trichloroethyl, 2,2,3,3-tetrafluoroethyl, and 2,2,2-trichloroethyl; preferably fluoromethyl, difluoromethyl, trifluoromethyl, trichloromethyl, difluorochloromethyl, and dichlorofluoromethyl.

[0030] Unless otherwise specified, the percentage content in this invention refers to the percentage content by mass.

[0031] This invention first provides a compound of formula I, its isomers, or salts thereof.

[0032] ,

[0033] I

[0034] R1 is selected from halogens or halogenated C1-C6 alkyl groups, preferably chlorine and trifluoromethyl, and particularly preferably chlorine.

[0035] The preferred compounds of this invention are as follows:

[0036] .

[0037] The preferred compound of this invention is .

[0038] The compounds particularly preferred by this invention exhibit unexpected technical effects in terms of insecticidal and bactericidal properties compared to compounds disclosed in the prior art.

[0039] The present invention also provides a pesticide composition, wherein the compound described herein isomer or salt thereof.

[0040] This invention also provides an application of the compound of this invention in the prevention and control of plant diseases.

[0041] This invention relates to the use of the compound or a composition containing the compound as a fungicide and insecticide in agriculture or horticulture for controlling or preventing beneficial plants from being affected by diseases and pests.

[0042] The diseases described in this invention include, but are not limited to, the following:

[0043] Oomycete diseases, such as downy mildew, white rust, damping-off, cottony rot, blight, and late blight;

[0044] Deuteromycete diseases, such as wilt, root rot, damping-off, anthracnose, verticillium wilt, black spot, gray mold, brown spot, black spot, leaf spot, early blight, ring spot, leaf blight, stem base rot, etc.

[0045] Basidiomycete diseases, such as rust and smut;

[0046] Ascomycete diseases, such as powdery mildew, sclerotinia rot (sclerotinia rot of flax, rapeseed, soybean, peanut, tobacco, pepper, eggplant, bean, pea, cucumber, bitter gourd, winter melon, watermelon, celery), and black spot, etc.

[0047] Compounds containing formula I or their salts as active ingredients can be used as nematicides to control nematodes in the soil of fruit trees, vegetables, other crops, and ornamental plants.

[0048] Examples of nematodes to which the nematicides of this invention can be applied include, but are not limited to, root-knot nematodes such as *Symplocos spp.*, *Cymplocos javanica*, *Cymplocos spp.*, and *Cymplocos spp.*; stem nematodes such as *Potato rot nematode* (stem rot nematode) and *Cymplocos spp.*; short-bodied nematodes such as *Northern root rot nematode* (piercing short-bodied nematode), *Chrysanthemum root rot nematode* (pseudo-short-bodied nematode), *Coffee root rot nematode* (coffee short-bodied nematode), *Tea root rot nematode* (Russ short-bodied nematode), and *Juglans regia* (damaged short-bodied nematode); and globular cyst nematodes such as *Golden nematode* (potato golden nematode). The nematodes include: potato cyst nematodes (potato white nematode); *Heterodera* nematodes such as soybean cyst nematode and beet cyst nematode; *Syngonium* nematodes such as rice tip nematode, chrysanthemum leaf bud nematode (chrysanthemum nematode), and strawberry nematode (strawberry nematode); *Eusynostella* nematodes such as fungi-eating nematode (oat true synostella); *Piercing Nematode* nematodes such as *Piercing Nematode* (banana piercing nematode); *Padna* nematodes such as citrus nematode (semi-piercing nematode); *Micrococcus* nematodes such as kidney-shaped micrococcus; and tree-borne nematodes such as pine wood nematode. Furthermore, the nematicidal composition of this invention is also effective against animal parasitic nematodes, such as ascarids, pinworms, *Anisakis*, filamentous nematodes, *Wuceta bancrystal*, *Cyclophorus*, and *Gnathostoma*.

[0049] The plant species that can be used with the compounds of this invention are not particularly limited; examples include, for instance, cereals (e.g., rice, barley, wheat, rye, oats, corn, sorghum, etc.), legumes (soybeans, mung beans, broad beans, peas, peanuts, etc.), fruit trees / fruits (apples, citrus, pears, grapes, peaches, Japanese apricots, cherries, walnuts, apricots, bananas, strawberries, etc.), vegetables (cabbage, tomatoes, spinach, cabbage, lettuce, onions, scallions, green peppers, etc.), and root vegetables (carrots, potatoes, sweet potatoes, radishes, etc.). (e.g., radish, lotus root, bulrush, etc.), industrial crops (e.g., cotton, hemp, paper mulberry, daphne, rapeseed, sugar beet, hops, sugarcane, sugar beet, olive, rubber, coffee, tobacco, tea, etc.), berries (e.g., pumpkin, cucumber, watermelon, melon, etc.), forage grasses (e.g., orchard grass, sorghum, timothy grass, alfalfa, purple alfalfa, etc.), turfgrass (e.g., Korean zoysia grass, creeping bentgrass, etc.), spice crops (e.g., lavender, rosemary, thyme, parsley, pepper, ginger, etc.), and flowers (e.g., chrysanthemum, rose, orchid, etc.).

[0050] The compounds of this invention are generally used as insecticidal active ingredients in compositions, i.e., formulations, and typically also include pesticide-acceptable surfactants and carriers. The carrier can be a solid carrier or a liquid carrier.

[0051] Suitable solid carriers include 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; silica, calcium carbonate, light calcium carbonate; calcium sulfate; limestone; sodium sulfate; ammonium salts, such as ammonium sulfate, hexamethylenediamine and urea, etc.

[0052] Liquid carriers include water and organic solvents. When water is used as a solvent or diluent, organic solvents can also be used as auxiliaries or antifreeze additives. Useful liquefied gaseous fillers or carriers are those liquids that are gaseous at standard temperatures and pressures, such as aerosol propellants like halogenated hydrocarbons, as well as butane, propane, nitrogen, and carbon dioxide, etc.

[0053] Suitable organic solvents include aromatic hydrocarbons, such as benzene, xylene, and toluene; chlorinated hydrocarbons, such as chlorobenzene, vinyl chloride, chloroform, and dichloromethane; aliphatic hydrocarbons, such as petroleum fractions, cyclohexane, and light mineral oils; alcohols, such as isopropanol, butanol, ethylene glycol, glycerol, and cyclohexanol; their ethers and esters; ketones, such as acetone, cyclohexanone, dimethylformamide, and N-methylpyrrolidone; vegetable oils, such as soybean oil, rapeseed oil, and cottonseed oil, etc.

[0054] Suitable surfactants (adjuvants, emulsifiers, dispersants, protective colloids, wetting agents, and binders) include all common ionic and nonionic substances, such as ethoxylated nonylphenol, polyalkylene glycol ethers of straight-chain or branched alcohols, reaction products of alkylphenols with ethylene oxide and / or propylene oxide, reaction products of fatty acid amines with ethylene oxide and / or propylene oxide, as well as fatty acid esters, alkyl sulfonates, alkyl sulfates, alkyl ether sulfates, alkyl ether phosphates, aryl sulfates, ethoxylated arylalkylphenols (such as tristyryl-phenol-ethoxylated compounds), and ethoxylated and propoxylated arylalkylphenols such as sulfated and phosphorylated arylalkylphenol-ethoxylated and -ethoxylated and -propoxylated compounds. Other examples are natural and synthetic water-soluble polymers, such as lignin sulfonates, gelatin, gum arabic, phospholipids, starch, hydrophobically modified starch, and cellulose derivatives, particularly cellulose esters and cellulose ethers, as well as polyvinyl alcohol, polyvinyl acetate, polyvinylpyrrolidone, polyacrylic acid, polymethacrylic acid, and copolymers of (meth)acrylic acid and (meth)acrylates, copolymers of methacrylic acid and methacrylates neutralized with alkali metal hydroxides, and optionally substituted naphthalene sulfonates condensates with formaldehyde. The presence of a surfactant is necessary if one of the active ingredients and / or one of the inert carriers is insoluble in water and the application is carried out in water.

[0055] The pesticide fungicide / insecticide described in this invention can be prepared by common methods. For example, the active substance is mixed with a liquid solvent and / or a solid carrier, and surfactants such as emulsifiers, dispersants, stabilizers, and wetting agents are added. Other adjuvants may also be added, such as binders, defoamers, foaming agents, antioxidants, crystallization inhibitors, viscosity modifiers, suspending agents, spray droplet modifiers, pigments, neutralizers and buffers, corrosion inhibitors, dyes, fragrances, spreading agents, penetration enhancers, micronutrients, dispersants, thickeners, freezing point depressants, antimicrobial agents, etc.

[0056] The pesticide fungicide / insecticide described in this invention can be applied in its formulation form or in an application form prepared therefrom. Such application forms include, but are not limited to, capsule suspensions, fine granules, foaming agents, pastes, suspension concentrates, emulsion concentrates, soluble concentrates, suspensions, wettable powders, soluble powders, powders and granules, water-soluble and water-dispersible granules or tablets, etc.

[0057] The formulations described in this invention may also contain other components, such as other fungicides, insecticides, herbicides, plant growth regulators, attractants, acaricides, nematicides, fertilizers, and safeners, which can be formulated together with liquid fertilizers or solid or granular fertilizer carriers such as ammonium nitrate and urea, or mixed with fine sand or soil.

[0058] When pesticide compositions containing compounds of Formula I of the present invention are used to control plant diseases and pests, the formulations may be emulsifiable concentrates, wettable powders, or microemulsions, etc., and are typically applied by diluting these formulations with water to a concentration of the active ingredient [i.e., the compound of Formula I of the present invention] in the range of 0.01 to 5000 ppm. Granules or powders can be applied without dilution. Research results show that the compounds of Formula I of the present invention, at concentrations of 0.01 to 100 ppm (0.01 mg / L to 100 mg / L), and preferably in the range of 0.01 ppm to 10 ppm, exhibit at least 90% inhibition or lethality against plant diseases and pests. Particularly preferred compounds exhibit at least 80% inhibition or lethality against certain diseases and pests in the range of 0.1 ppm to 1.5 ppm.

[0059] I. Preparation Examples

[0060] In this specification, if there are any differences between chemical names and chemical structures, the structure is preferred. Generally, the compounds of this invention can be prepared by the methods described herein, unless further specified. The raw materials, reagents, etc., used to prepare the compounds of this invention are commercially available or can be prepared by methods conventional in the art.

[0061] Example 1 Synthesis of N-(1-(3,5-dichloropyridin-2-yl)cyclopropyl)methyl)-2-(difluoromethyl)benzamide (compound I-1)

[0062] (1) Synthesis of methyl 2-cyano-2-(3,5-dichloropyridin-2-yl)acetate

[0063]

[0064] In a 250ml four-necked flask equipped with a stirrer, thermometer, and condenser, add DMF (100ml), 2,3,5-trichloropyridine (18.2g, 0.1mol), potassium carbonate (16.6g, 0.12mol), and dropwise add methyl cyanoacetate (14.9ml, 0.15mol). Heat to 110°C. o C. After reacting for 8 hours, the HPLC monitoring showed that the reactant was less than 10% remaining. The mixture was diluted with water (300 ml), extracted with ethyl acetate (100 ml x 3), washed with saturated brine (100 ml x 3), concentrated under reduced pressure, and purified by column chromatography to obtain methyl 2-cyano-2-(3,5-dichloropyridin-2-yl)acetate (15 g, 0.061 mol), a yellow solid, with a yield of 61%.

[0065] (2) Synthesis of 2-(3,5-dichloropyridin-2-yl)acetonitrile

[0066]

[0067] In a 250 ml four-necked flask equipped with a stirrer, thermometer, and condenser, methanol (100 ml), methyl 2-cyano-2-(3,5-dichloropyridin-2-yl)acetate (15 g, 0.061 mol), and 50% sulfuric acid aqueous solution (100 ml) were added. The mixture was heated under reflux for 24 hours. The reaction was monitored by HPLC until it ended. The mixture was diluted with water (300 ml), extracted with ethyl acetate (100 ml x 3), washed with saturated brine (100 ml x 3), concentrated under reduced pressure, and purified by column chromatography of the crude product to obtain 2-(3,5-dichloropyridin-2-yl)acetonitrile (10 g, 0.054 mol), a pale yellow oily liquid, with a yield of 89%.

[0068] (3) Synthesis of 1-(3,5-dichloropyridin-2-yl)cyclopropane-1-onitrile

[0069]

[0070] Add 100ml of DMF to a 250ml four-necked flask equipped with a stirrer, thermometer, and condenser. 2-(3,5-dichloropyridin-2-yl)acetonitrile (10 g, 0.054 mol) was cooled to below 0 °C, and 60% sodium hydride (5 g, 0.125 mol) was added in portions. The reaction temperature did not exceed 30 °C. After the addition was complete, the mixture was stirred at room temperature for 15 minutes. Then, 1,2-dibromoethane (13 g, 0.07 mol) was slowly added dropwise. The reaction temperature did not exceed 30 °C. After the addition was complete, the mixture was stirred at room temperature for 4 hours. The reaction was monitored by HPLC until complete. The reaction was quenched by adding 20 ml of saturated ammonium chloride aqueous solution to the reaction solution. The mixture was diluted with water (300 ml), extracted with ethyl acetate (100 ml x 3), washed with saturated brine (100 ml x 3), concentrated under reduced pressure, and purified by column chromatography of the crude product to obtain 1-(3,5-dichloropyridin-2-yl)cyclopropane-1-onitrile (10 g, 0.047 mol), a pale yellow solid, with a yield of 87%.

[0071] (4) Synthesis of (1-(3,5-dichloropyridin-2-yl)cyclopropyl)methylamine

[0072]

[0073] In a 250 ml autoclave, methanol (100 ml), Raney nickel (1 g), a 7 M ammonia methanol solution (8.7 ml, 0.06 mol), and 1-(3,5-dichloropyridin-2-yl)cyclopropane-1-onitrile (10 g, 0.047 mol) were added. Hydrogen gas was introduced, and the mixture was heated to 30 °C for 8 hours. The reaction was monitored by HPLC until it ended. The mixture was then filtered, concentrated, and 11 g of crude 1-(3,5-dichloropyridin-2-yl)cyclopropyl)methylamine was obtained as an oily liquid.

[0074] (5) Synthesis of N-(1-(3,5-dichloropyridin-2-yl)cyclopropyl)methyl)-2-(difluoromethyl)benzamide

[0075]

[0076] In a 250 ml four-necked flask equipped with a stirrer, thermometer, and condenser, THF (50 ml), crude 1-(3,5-dichloropyridin-2-yl)cyclopropyl)methylamine (3 g, 0.014 mol), 2-difluoromethylbenzoic acid (2.49 g, 0.014 mol), HATU (8.0 g, 0.021 mol), and TEA (2.2 g, 0.021 mol) were added. The mixture was reacted at room temperature for 4 hours. The reaction was monitored by HPLC until it ended. The mixture was diluted with water (150 ml), extracted with ethyl acetate (50 ml x 3), washed with saturated brine (50 ml x 3), concentrated under reduced pressure, and purified by column chromatography to obtain N-(1-(3,5-dichloropyridin-2-yl)cyclopropyl)methyl)-2-(difluoromethyl)benzamide (3 g, 0.008 mol), a white solid, with a yield of 58%. 1 H NMR (500 MHz, DMSO-d6) δ 8.71 (t, J = 6.2 Hz, 1H), 8.51 – 8.41 (m, 1H), 8.17 (d, J = 2.2 Hz, 1H), 7.68 (dd, J = 8.7, 4.9Hz, 1H), 7.65 – 7.56 (m, 2H), 7.55 – 7.47 (m, 1H), 6.99 (t, J = 55.6 Hz, 1H), 3.58 (d, J = 6.2 Hz, 2H), 1.09 – 1.06 (m, 2H), 0.94-0.90 (m, 2H).

[0077] Example 2 Synthesis of N-(1-(3-chloro-5-trifluoromethylpyridin-2-yl)cyclopropyl)methyl)-2-(difluoromethyl)benzamide (compound I-2)

[0078] (1) Synthesis of methyl 2-cyano-2-(3-chloro-5-trifluoromethylpyridin-2-yl)acetate

[0079]

[0080] In a 250 ml four-necked flask equipped with a stirrer, thermometer, and condenser, DMF (100 ml), 5-trifluoromethyl-2,3-dichloropyridine (21.6 g, 0.1 mol), and potassium carbonate (16.6 g, 0.12 mol) were added. Methyl cyanoacetate (14.9 ml, 0.15 mol) was added dropwise. The mixture was heated to 110 °C and reacted for 8 hours. The reaction was monitored by HPLC until it ended. The mixture was diluted with water (300 ml), extracted with ethyl acetate (100 ml x 3), washed with saturated brine (100 ml x 3), concentrated under reduced pressure, and purified by column chromatography to obtain methyl 2-cyano-2-(3-chloro-5-trifluoromethylpyridin-2-yl)acetate (25 g, 0.09 mol), with a yield of 90%.

[0081] (2) Synthesis of 2-(3-chloro-5-trifluoromethylpyridin-2-yl)acetonitrile

[0082]

[0083] In a 250 ml four-necked flask equipped with a stirrer, thermometer, and condenser, methanol (100 ml), methyl 2-cyano-2-(3-chloro-5-trifluoromethylpyridin-2-yl)acetate (15 g, 0.054 mol), and 50% sulfuric acid aqueous solution (100 ml) were added. The mixture was heated under reflux for 24 hours. After the reaction was completed as monitored by HPLC, the mixture was diluted with water (300 ml), extracted with ethyl acetate (100 ml x 3), washed with saturated brine (100 ml x 3), concentrated under reduced pressure, and purified by column chromatography to obtain 2-(3-chloro-5-trifluoromethylpyridin-2-yl)acetonitrile (10.8 g, 0.049 mol), a white solid, with a yield of 91%.

[0084] (3) Synthesis of 1-(3-chloro-5-trifluoromethylpyridin-2-yl)cyclopropane-1-onitrile

[0085]

[0086] In a 250ml four-necked flask equipped with a stirrer, thermometer, and condenser, add 100ml of DMF and 10.8g (0.049mol) of 2-(3-chloro-5-trifluoromethylpyridin-2-yl)acetonitrile. Cool the system to 0°C. o Add sodium hydride (5g, 0.125mol) with a 60% content in batches below 30°C, and the reaction temperature should not exceed 30°C. o C. After the addition is complete, stir at room temperature for 15 minutes, then slowly add 1,2-dibromoethane (13g, 0.07mol) dropwise, keeping the reaction temperature below 30°C. oC. After the addition was complete, the mixture was stirred at room temperature for 4 hours. The reaction was monitored by HPLC until it ended. The reaction was quenched by adding saturated ammonium chloride aqueous solution (20 ml). The mixture was diluted with water (300 ml), extracted with ethyl acetate (100 ml x 3), washed with saturated brine (100 ml x 3), concentrated under reduced pressure, and purified by column chromatography of the crude product to obtain 1-(3-chloro-5-trifluoromethylpyridin-2-yl)cyclopropane-1-onitrile (10 g, 0.040 mol), a white solid with a yield of 82%.

[0087] (4) Synthesis of (1-(3-chloro-5-trifluoromethylpyridin-2-yl)cyclopropyl)methylamine

[0088]

[0089] In a 250 ml autoclave, methanol (100 ml), Raney nickel (1 g), a 7 M ammonia methanol solution (8.7 ml, 0.06 mol), and 1-(3-chloro-5-trifluoromethylpyridin-2-yl)cyclopropane-1-onitrile (10 g, 0.04 mol) were added. Hydrogen gas was introduced, and the mixture was heated to 30 °C for 8 hours. After the reaction was completed by HPLC monitoring, the mixture was filtered and concentrated to obtain 11 g of crude (1-(3-chloro-5-trifluoromethylpyridin-2-yl)cyclopropyl)methylamine, which was an oily liquid.

[0090] (5) Synthesis of N-(1-(3-chloro-5-trifluoromethylpyridin-2-yl)cyclopropyl)methyl)-2-(difluoromethyl)benzamide

[0091]

[0092] In a 250 ml four-necked flask equipped with a stirrer, thermometer, and condenser, 50 ml of THF, crude (1-(3-chloro-5-trifluoromethylpyridin-2-yl)cyclopropyl)methylamine (3 g, 0.012 mol), 2-difluoromethylbenzoic acid (2.11 g, 0.012 mol), HATU (6.84 g, 0.018 mol), and TEA (1.8 g, 0.018 mol) were added. The mixture was reacted at room temperature for 4 hours under HPLC monitoring. After dilution with 300 ml of water, extraction with ethyl acetate (100 ml x 3), washing with saturated brine (100 ml x 3), concentration under reduced pressure, and purification by column chromatography of the crude product, N-(1-(3-chloro-5-trifluoromethylpyridin-2-yl)cyclopropyl)methyl)-2-(difluoromethyl)benzamide (3 g, 0.007 mol) was obtained as a white solid with a yield of 61%. 1H NMR (500 MHz, DMSO-d6) δ 8.79 (d, J = 2.0Hz, 1H), 8.76 (t, J =6.3 Hz, 1H), 8.41 (d, J = 2.1 Hz, 1H), 7.69 – 7.64 (m,1H), 7.64 – 7.57 (m, 2H), 7.57 – 7.46 (m, 1H), 6.88 (t, J = 55.7 Hz, 1H), 3.64 (d, J = 6.3 Hz, 2H), 1.13 – 1.10 (m, 2H), 0.99-0.97 (m, 2H).

[0093] The control compound CK was synthesized according to the above embodiments, as shown in Table 1.

[0094] Table 1. Comparison Compounds

[0095]

[0096] II. Bioactivity Assay

[0097] 1) Assay for the nematode-killing activity of southern root-knot nematodes

[0098] 1. Test reagents

[0099] Compounds I-1, I-2 and the control compound (CK) were prepared in the applicant's laboratory.

[0100] 2. Preparation of pharmaceuticals

[0101] Pharmaceutical preparation: Dissolve the compound of the present invention and the reference drug in acetone, then add Tween 80 and dilute with water to the corresponding mass concentrations: 5.000 ppm, 2.500 ppm, 1.250 ppm and 0.625 ppm for later use.

[0102] 3. Test target preparation

[0103] Plant large-leaf water spinach in areas severely affected by root-knot nematodes. After 3 months of planting, remove the above-ground parts, wash the roots, prepare a solution containing 1% food-grade brilliant blue, soak the water spinach roots in the brilliant blue solution for 10 minutes, rinse with clean water, and the nematode eggs will turn blue. Pick out the eggs with tweezers and put them in clean water. The eggs will hatch into nematodes. Use the solution of nematodes that have hatched for 2 days for testing, and use the eggs picked out on the same day for testing.

[0104] 4. Life test

[0105] 100 μL of the hatched nematodes or egg fluid was placed into the wells of a culture plate. 100 μL of each of the prepared drug concentrations was added to the culture plate. The room temperature was maintained at 25°C during the experiment. Each concentration was replicated three times, with observations at 24 h and 48 h. A blank control (water without the drug) was provided.

[0106] 5. Survey and statistics

[0107] Statistical analysis of root-knot nematodes: Under stereomicroscopic examination at various concentrations, the total number of nematodes and the number of dead nematodes were recorded over 24 hours, and the mortality rate was calculated. The nematode mortality criterion was that the nematode body appeared as a straight or wavy line and showed no movement within 30 seconds.

[0108] Statistical analysis of root-knot nematode eggs: The total number of nematode eggs that hatched after 48 hours was examined under a stereomicroscope at various concentrations, and the inhibition rate of the compound on nematode egg hatching was calculated.

[0109] Mortality rate (%) = (Number of dead nematodes / Total number of nematodes) × 100%;

[0110] Corrected mortality rate (%) = (treatment nematode mortality rate - control nematode mortality rate) / (1 - control nematode mortality rate) × 100%.

[0111] Relative inhibition rate (%) = (number of control hatched nematodes - number of treatment hatched nematodes) / number of control hatched nematodes × 100%.

[0112] Table 2. Indoor activity results of root-knot nematodes.

[0113]

[0114] Table 3. Indoor viability results of root-knot nematode eggs

[0115]

[0116] (ii) Indoor activity test against Fusarium graminearum

[0117] (1) Test strains

[0118] Fusarium graminearum was isolated, purified, identified, and preserved in our laboratory.

[0119] (2) Pharmaceutical preparation

[0120] The required amounts of compound I-1, compound I-2, and control compound (CK) were calculated based on the content of the active ingredient and prepared into a high-concentration stock solution of 10,000 ppm by adding water. This stock solution was then diluted to the corresponding concentration. If the original drug showed poor solubility during preparation, an appropriate amount of organic solvent could be added to aid dissolution. Five concentration gradients were set up: 100 ppm, 50 ppm, 25 ppm, 12.5 ppm, and 6.25 ppm.

[0121] (3) Experimental methods

[0122] The preparation process for the PDA culture medium required in the experiment is as follows: Weigh 40.1g of PDA culture medium powder and dissolve it completely in 1L of sterile water. After complete dissolution, dispense 200mL of culture medium into Erlenmeyer flasks, then sterilize them in an autoclave before use. Prepare the corresponding amount of culture medium according to the experimental dosage.

[0123] The prepared stock solution was diluted to a suitable concentration and mixed with sterilized PDA medium at a certain ratio to prepare a series of drug-containing PDA mediums with varying concentrations. These mediums were then evenly poured into 8.5cm petri dishes and inoculated with bacterial pellets. Drug-free PDA medium was used as a blank control. Each treatment was replicated three times.

[0124] (4) Survey, recording and measurement methods

[0125] After applying the medication and inoculating the bacteria, at 25 o After incubation at constant temperature for 7 days, the colony diameter was investigated using the cross-sectional method. The average diameter of each treatment colony was calculated, and the inhibition rate was calculated using the following formula:

[0126] Inhibition rate (%) = (Control colony diameter - Treated colony diameter) / (Control colony diameter - Mycelial cake diameter) × 100%

[0127] Note: The diameter of the mushroom cake is usually 1cm.

[0128] Table 4. Indoor activity test efficacy of compounds against Fusarium graminearum

[0129]

[0130] III) Efficacy test of drugs for controlling root-knot nematode disease in potted cucumbers

[0131] (1) Calculate the required amounts of compound I-1, compound I-2, and control compound (CK) according to the content of active ingredients, and prepare a high-concentration 10% stock solution. Then dilute with water to the corresponding concentration. If the original drug has poor solubility during preparation, an appropriate amount of organic solvent can be added to aid dissolution. Set three concentration gradients: 50 ppm, 25 ppm, and 12.5 ppm.

[0132] (2) Test conditions

[0133] The experimental subject was root-knot nematode (Meloidogyne), and the crop was cucumber (variety: Miaoshou). The experiment was conducted in a constant temperature incubation room. The potted cucumbers were in the 3-4 true leaf stage, and all plants were managed with the same fertilizer and water, resulting in uniform growth, making it suitable for conducting experiments on the control of root-knot nematode disease in potted plants with different concentrations.

[0134] (3) Experimental arrangement

[0135] Each treatment consisted of four pots, with one pot serving as a replicate. A blank control (water) was included. 300 ml of water was used per planting hole. The cultivated cucumber seedlings were transplanted into potted soil. Once the seedlings had 3-4 true leaves, the experiment was conducted. Approximately 2000 nematodes hatched indoors were inoculated into each pot. Seven days after inoculation, the roots were drenched with the nematode solution. This was followed by three more inoculations, each one week apart, for a total of four inoculations.

[0136] (4) Measurement method

[0137] Potted plants were placed in a constant-temperature incubation room at 27℃ with 12 hours of light per day. Watering was normal during the experiment. The experimental soil was loam with a pH of 6.7. A follow-up survey was conducted 60 days after inoculation to count the number of root knots in each treatment.

[0138] Therapeutic effect (%) = {(mean number of root knots in blank control - mean number of root knots in treatment) / mean number of root knots in blank control} * 100%

[0139] Table 5. Therapeutic effects of compounds on cucumber root-knot nematode disease

[0140]

[0141] As shown in Table 5, the compounds of this invention have a good therapeutic effect on cucumber root-knot nematode disease.

[0142] The preferred embodiments of the present invention have been described in detail above; however, the present invention is not limited thereto. Within the scope of the inventive concept, various simple modifications can be made to the technical solutions of the present invention, including combinations of various technical features in any other suitable manner. These simple modifications and combinations should also be considered as the content disclosed in the present invention and are all within the protection scope of the present invention.

Claims

1. A compound or a salt thereof, characterized in that, Selected from the following compounds, 。 2. A pesticide composition, characterized in that, Contains the compound of claim 1 or a salt thereof.

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