Derivatives of targeted pyruvate kinase as well as preparation method and application of derivatives

Abstract

The invention relates to a pyruvate kinase-targeted compound shown as a formula I, a preparation method and application thereof, and application of the pyruvate kinase-targeted compound serving as a plant antibacterial agent, and part of the pyruvate kinase-targeted compound shows excellent bactericidal activity.

Description

Technical Field

[0001] This invention belongs to the field of pesticide chemistry, specifically relating to thiazole-containing diamide derivatives that target pyruvate kinase, their preparation methods, and uses. Background Technology

[0002] Crop production relies heavily on the use of chemical pesticides to manage insects, plant pathogens, and weeds that affect crop yields. Chemical pesticides, with their high efficiency and relatively low cost, have become a significant driver of increased yields per unit area of ​​farmland. However, the intense selective pressures imposed by chemical pesticides, coupled with a lack of effective resistance management practices, have led to the widespread evolution of resistance to these pesticides in insects, plant pathogens, and weeds. Therefore, there is an increasing need for effective and safe pesticides with novel molecular targets to address the evolving resistance of insects, plant pathogens, and weeds and ensure food security.

[0003] Based on the previously discovered highly bactericidal compound YZK-C22, this study utilized new life science technologies to identify its target as pyruvate kinase (Zhao B, et al.). J. Agric. Food Chem. ,2018, 66: 12439 12452; Zhao B, and others , Food and Agricultural Immunology 2019, 30(1): 533-547). Pyruvate kinase, as a novel potential fungicide target, is of great significance for the creation of new pesticides, especially new fungicides. The inventors previously discovered a series of novel 1,3,4-oxadiazole-thiazolium lead compounds that target pyruvate kinase, providing new options and feasible solutions for the research on the creation of new pesticides. Summary of the Invention

[0004] The purpose of this invention is to provide a thiazole-containing diamide derivative that targets pyruvate kinase.

[0005] The first aspect of this invention provides a compound of Formula I, or a stereoisomer thereof, or an agriculturally chemically acceptable salt thereof: ; Formula I; R1 is selected from C1-C6 straight-chain or branched alkyl groups, halogen-substituted C1-C6 straight-chain or branched alkyl groups, C3-C6 cycloalkyl groups, and C6-C6 cycloalkyl groups. 12 Aryl groups or C5-C groups containing N, O, or S atoms 12 heteroaryl; the C5-C 12 Aryl groups or C6-C groups containing N, O, or S atoms 12The heteroaryl group can be further optionally influenced by one, two, or three independent R groups. 1a replace, R 1a Selected from hydrogen, halogens, or C1-C6 straight-chain or branched alkyl groups; R2 is selected from C6-C 12 Aryl, C6-C 12 Aryl groups or C5-C groups containing N, O, or S atoms 12 heteroaryl; the C6-C 12 Aryl, C5-C 12 Aryl groups or C5-C groups containing N, O, or S atoms 12 The heteroaryl group can be further optionally influenced by one, two, or three independent R groups. 2a replace; R 2a Selected from hydrogen, halogen, halogen-substituted C1-C6 straight-chain or branched alkyl groups or C1-C6 straight-chain or branched alkyl groups.

[0006] Preferably, the compound of formula I is selected from the following structures. or ; Formula Ia and Formula Ib.

[0007] More preferably, R1 is selected from cyclopropyl, trifluoromethyl, phenyl, or naphthyl; the phenyl or naphthyl group may be optionally replaced by one, two, or three independent R1 groups. 1a replace, R 1a Selected from halogens; And / or, R2 is selected from phenyl, pyridyl, isothiazolyl, or thiophene; said phenyl, pyridyl, isothiazolyl, or thiophene The base can be further optionally assigned to one, two, or three independent R. 2a replace; R 2a Selected from halogens, halogen-substituted C1-C6 straight-chain or branched alkyl groups, or C1-C6 straight-chain or branched alkyl groups.

[0008] Further preferred: R1 is selected from -CF3 , or ; R2 is selected from , , , , , , , , or .

[0009] The present invention provides the compound of Formula I, specifically as follows: .

[0010] A second aspect of the present invention provides a pesticide composition comprising the compound of formula I, formula Ia, formula Ib, or a stereoisomer thereof, or an agriculturally chemically acceptable salt thereof, and a carrier; wherein the carrier is in liquid or solid form.

[0011] The third aspect of the present invention provides the application of the compound of formula I, the compound of formula Ia, the compound of formula Ib or their stereoisomers, or their agriculturally chemically acceptable salts or the pesticide composition thereof in the control of plant fungal diseases. Preferably, the plant fungal diseases are pathogens of early blight of tomato, Botrytis cinerea, brown spot of peanut, Fusarium graminearum, ring rot of apple, Rhizoctonia solani, Fusarium oxysporum, Fusarium verticillata, or Sclerotinia sclerotiorum.

[0012] The fourth aspect of the present invention is a bactericide, characterized in that the bactericide contains a bactericidal effective amount of at least one of the following: a compound of formula I, a compound of formula Ia, a compound of formula Ib or a stereoisomer thereof, or an agriculturally chemically acceptable salt thereof, and optionally contains excipients.

[0013] More preferably, the formulation of the bactericide is selected from at least one of emulsifiable concentrate, suspension concentrate, wettable powder, powder, granule, aqueous solution, mother liquor, and masterbatch.

[0014] The fifth aspect of the present invention provides a method for controlling or preventing the infection of useful plants by plant pathogenic microorganisms, wherein an effective amount of the said compound having formula I, formula Ia, formula Ib, or a composition containing such compound as an active ingredient is applied to the plant, its parts, or its location.

[0015] The sixth aspect of the present invention provides the following preparation method, ; Thioxamid ethyl ester was dissolved in anhydrous ethanol. Compound 1-cyclopropyl-2-bromoethylone I-1a was added dropwise under stirring at room temperature. After the addition was complete, the reaction system was transferred to an oil bath and heated under reflux. The reaction was monitored by TLC. After the reaction was complete, the solvent was removed by rotary evaporation, and the mixture was dissolved in an appropriate amount of ethyl acetate. The solution was washed twice with saturated sodium chloride solution, and the organic layer was dried over anhydrous sodium sulfate. After vacuum filtration, the residue was treated with petroleum ether / ethyl acetate (3:1 to 5:1) with a boiling range of 60–90 °C. yes / yes Using 100-200 mesh silica gel column chromatography as the eluent, intermediate I-2a was obtained.

[0016] Compound I-2a was dissolved in anhydrous ethanol, and 80% hydrazine hydrate was added dropwise under stirring at room temperature. After the addition was complete, the reaction system was transferred to an oil bath and heated under reflux. The reaction was monitored by TLC. After the reaction was complete, the mixture was cooled to room temperature and stirred for another 1-2 hours to obtain a large amount of solid. The solid intermediate I-3a was obtained by vacuum filtration.

[0017] Intermediate I-3a was dissolved in dichloromethane with 2-chloronicotinyl chloride and triethylamine, and then reacted at room temperature. After the reaction was complete, the mixture was extracted with a saturated sodium bicarbonate solution, followed by extraction with dichloromethane. The combined organic layers were washed with a saturated sodium chloride solution and dried over anhydrous sodium sulfate. The residue was filtered under reduced pressure and then treated with petroleum ether / ethyl acetate (1:1 to 3:1) with a boiling range of 60–90 °C. yes / yes Using 1 / 2 as the eluent, the target compound I was obtained by silica gel column chromatography.

[0018] The seventh aspect of this invention provides the application of compounds of formula I, Ia, and Ib in combination with insecticides for the control of agricultural, forestry, and horticultural plant pests: The compounds of formula I, Ia, and Ib of this invention are combined with any one or two commercial insecticides to form an insecticidal composition for the control of agricultural, forestry, and horticultural plant pests, wherein the commercial insecticide is selected from: imidacloprid, difenoconazole, acetamiprid, emamectin benzoate, mibamectin, abamectin, spinosad, and heptapoxetine. Flufenoxam, cypermethrin, lambda-cyhalothrin, deltamethrin, cypermethrin, β-cypermethrin, λ-cypermethrin, dichlorvos, permethrin, allethrin, bifenthrin, permethrin, fenpyroxene, flufenoxuron, flufenoxuron, imidacloprid, acetamiprid, chlorpyrifos, thiamethoxam, thiamethoxam, dinotefuran, fenpropathrin, diflubenzuron, diflubenzuron, diflubenzuron, flufenoxuron, flufenoxuron, flufenoxuron, acetamiprid, lufenuron , including chlorfenapyr, flufenoxuron, polyfluorourea, flufenoxuron, diphenylfluorourea, flufenoxuron, fenflurfen, fenflurfen, furazolidone, chlorfenapyr, methoxyfenozide, cyclophosphamide, dichlorvos, quinalphos, pyridaben, leafhopper spray, carbaryl, imidacloprid, isoprocarb, pymetrozine, methyl parathion, methyl parathion, bromopropylate, thiamethoxam, azoxystrobin, pyridaben, tetradifon, propargite, difenoconazole, pymetrozine, spirodiclofen, spirotetramat, triazophos, thiamethoxam, and more. The insecticides include: imidacloprid, chlorfenapyr, tetrachlorfenapyr, flufenoxuron, flufenoxuron, cyanfenoxuron, butenpyram, azoxystrobin, bromonoxin, pyrazinone, etoxazole, pyridaben, pyriproxyfen, emamectin, pendimethalin; the compound containing formula I, formula Ia, and formula Ib of the present invention has a mass percentage content of 1%-90% in the insecticidal composition, and the ratio of the compound containing formula I, formula Ia, and formula Ib of the present invention to the aforementioned commercial insecticides is 1% by mass. 99% to 99% 1%; the formulation of the insecticidal composition is selected from: seed treatment emulsions, water-in-oil emulsions, microemulsions, suspensions, capsule suspensions, water-soluble granules, fine granules, soluble concentrates, poisoned grains, block poisoned baits, granular poisoned baits, flake poisoned baits, concentrated poisoned baits, slow-release blocks, electrostatic sprays, oil-in-water emulsions, smoke cans, smoke candles, smoke tubes, smoke sticks, smoke sheets, smoke pellets, gas generators, ointments, thermal fogging agents, cold fogging agents, aerosols, solid / liquid mixtures, liquid / liquid mixtures, solid / solid mixtures, medicated paints, microparticles, tracking powders, oil suspensions, oil-dispersible powders, concentrated gels, spraying agents, seed coating agents, smearing agents, film-forming oils, ultra-low volume liquids, vapor release agents; the plant pests for which the insecticidal composition is applicable are selected from: *Gnaphalium affine*. Noctuid moth, spider mite, Oriental migratory locust, spotted locust, Chinese rice locust, Japanese yellow-spined locust, single-spined mole cricket, oriental mole cricket, rice thrips, tobacco thrips, greenhouse thrips, rice tube thrips, wheat tube thrips, greenhouse whitefly, tobacco whitefly, black-tailed leafhopper, large green leafhopper, cotton leafhopper, spotted lanternfly, brown planthopper, white-backed planthopper, gray planthopper, sugarcane flat-horned planthopper, cotton aphid, wheat two-forked aphid, wheat Long-tubed aphid, peach aphid, sorghum aphid, radish aphid, cottony cushion scale, mulberry shield scale, arrowhead shield scale, pear round scale, white wax insect, red wax scale, Korean ball scale, pear lace bug, banana lace bug, slender horned flower bug, small flower bug, needle-edged bug, rice spider-edged bug, rice brown bug, rice black bug, rice green bug, green mirid bug, alfalfa mirid bug, medium black mirid bug, large lacewing, beautiful lacewing, Chinese lacewing, grain moth, clothes moth, yellow spiny bug. Moths, including brown tussock moth, flat tussock moth, wheat moth, cotton bollworm, sweet potato wheat moth, diamondback moth, peach fruit moth, soybean fruit moth, peach fruit moth, apple top leafroller, brown-banded long leafroller, false yellow leafroller, rice stem borer, soybean pod borer, corn borer, three-spined rice stem borer, cabbage stem borer, rice leaf roller, striped stem borer, cotton leaf roller, peach borer, armyworm, beet armyworm, rice stem borer, and cotton leaf roller. Bridge worms, beet armyworm, corn borer, cotton bollworm, *Dalbergia odorifera*, small cutworm, large cutworm, yellow cutworm, tussock moth, gypsy moth, sweet potato hawk moth, bean hawk moth, straight-striped rice skipper, hidden-striped rice skipper, citrus swallowtail butterfly, white-banded swallowtail butterfly, cabbage white butterfly, ramie red nymph, ramie yellow nymph, bean blister beetle, golden ground beetle, wrinkled sheath beetle, wheat ear ground beetle, furrow wireworm, slender-breasted wireworm. Millet beetle, black beetle, citrus shrew beetle, golden-edged shrew beetle, yellow mealworm, black mealworm, red flour beetle, mixed flour beetle, green scarab beetle, dark scarab beetle, North China large black-breasted scarab beetle, mulberry longhorn beetle, star longhorn beetle, orange brown longhorn beetle, peach red-necked longhorn beetle, large ape leaf beetle, small ape leaf beetle, yellow cucumber beetle, yellow striped flea beetle, green bean weevil, pea weevil, broad bean weevil, corn weevil, rice weevil, wheat Sawflies, pear fruit wasps, yellow-banded ichneumon wasps, armyworm white-spotted ichneumon wasps, larval ichneumon wasps, cotton bollworm toothed ichneumon wasps, larval black-spotted wart ichneumon wasps, mosquitoes, flies, horseflies, wheat red midge, wheat yellow midge, rice gall midge, citrus fruit fly, melon fruit fly, wheat leaf leafminer, American serpentine leafminer, bean stalk black leafminer, wheat straw fly, seed fly, onion fly, turnip fly, umbrella-skirted parasitic fly, corn borer parasitic fly, armyworm;The insecticidal composition is suitable for use with plants selected from: rice, wheat, barley, oats, corn, sorghum, sweet potato, potato, cassava, soybean, snow pea, broad bean, pea, mung bean, adzuki bean, cotton, silkworm, peanut, rapeseed, sesame, sunflower, beet, sugarcane, coffee, cocoa, ginseng, fritillaria, rubber, coconut, oil palm, sisal, tobacco, tomato, chili pepper, radish, cucumber, cabbage, celery, pickled mustard greens, beet, rapeseed, onion, garlic, watermelon, cantaloupe, honeydew melon, papaya, apple, citrus and peach trees, tea, wild vegetables, bamboo shoots, hops, pepper, banana, papaya, orchid, and bonsai.

[0019] This invention also provides the application of compounds containing formula I, Ia, and Ib in combination with fungicides in the prevention and control of diseases in agricultural, forestry, and horticultural plants. The fungicides of this invention, in combination with any one or two of commercial fungicides, form a fungicidal composition for the prevention and control of diseases in agricultural, forestry, and horticultural plants. The commercial fungicides are selected from: benzothiadiazole, thiamethoxam, methyl thiamethoxam, isothiazamide, ribavirin, antofenfen, ningnanmycin, or salicylic acid, cymoxanil, thiram, thiram, mancozeb, fosetyl-aluminum, thiophanate-methyl, chlorothalonil, dichlorvos, iprodione, benzyl benzoate, thiophanate-methyl, thiophanate-methyl, metalaxyl, flumorph, dimethomorph, high-efficiency metalaxyl, high-efficiency benzyl benzoate, etc. Cyclofenac, Sulfovir, Methoxyfenac, Thifluzamide, Leaf blight phthalate, Cyclopropionyl amide, Cyclofluzamide, Cyclopyridamole, Cyclopyridamole, Silthiazamide, Carbendazim, Oxychlorophenoxyacetic acid, Carbendazim, Mefluzamide, Carbendazim, Fluopyram, Furapilamide, Thifluzamide, Cyclopyridamole, Pyrimethanil, Pyraclostrobin, Bifenopyram, Fluopyram, Fluopyram, Fluopyram Fluopyram, benzylfluopyram, isothiazamide, fluopyram hydroxylamine, fluopyram, fluopyram, dimethomorph, benzylfluopyram, ethoxysulfuron, iprodione, pyraclostrobin, fenpyroxime, fluopyram, fenpyroxime, fenpyroxime, pyraclostrobin, azoxystrobin, fenpyroxime, oxadiazon, fenpyroxime, fenpyroxime, oxadiazon, furazolidone, cyproconazole, difenoconazole Cycloazole, Tebuconazole, High-efficiency Tebuconazole, Fluconazole, Cyproconazole, Fluquinazole, Flusilazole, Tebuconazole, Hexaconazole, Imidazole, Izoxystrobin, Imidazole, Tebuconazole, Cyproconazole, Tebuconazole, Prothioconazole, Silozolid, Tebuconazole, Tebuconazole, Tebuconazole, Triadimefon, Mefenoxam, Bifenthrin, Thiamethoxam, Mefenoxam, Imazalil, High-efficiency Imazalil, Prochloraz, Fluconazole, Cyazofamid, Imazalil Azoxystrobin, oxadiazon, isoprothiolane, oxadiazon, pyraclostrobin, oxadixyl, oxazolidinone, thiamethoxam, terbufos, fenthiamethoxam, dodecyl morpholine, butyl morpholine, tridemorpholine, seed dressing agent, fludioxonil, fluazinam, pyridaben, cyclopyridam, fluazinam, pyridaben, pyrimethanil, pyrimethanil, thifluzamide, pyrimethanil, pyrimethanil, chlorpyrifos, fluazinam Pyrimidinol, acaricide, dicyandioxanone, ethoxyquinoline, hydroxyquinoline, propoxyquinoline, phenoxyquinoline, ethoxycarb, isopropoxyl, benomyl, cymoxanil, sulfadiazine, difenoconazole, isoprothiolane, pyraclostrobin, methyl thiophanate, kasugamycin, polyoxin, polyoxin, effectivemycin, jinggangmycin, streptomycin, metalaxyl, furazolidone, benzalkonium chloride, furazolidone, carbendazim, benomyl, thiophanate-methyl, triadimefon, ethirimol sulfonate, dimethomorph, ethirimol, captan, captan, vinclozolin, fluchlorothalonil, chlorothalonil, isoprothiolane, isoprothiolane, tebuconazole, pentachloronitrobenzene, propineb, aluminum tris(ethylphosphonate), sulfur, Bordeaux mixture, copper sulfate, copper oxychloride, cuprous oxide, copper hydroxide, benomyl.The fungicides include: pendimethalin, pyridaben, tetrachlorophthalide, quinclorac, spirocycline, tricyclazole, pyrazosulfuron, doxycycline, biguanidine octyl salt, biguanidine octylamine, chlorpyrifos, benzylsulfamethoxam, toluenesulfonamide, indole ester, sodium dichloroisocyanurate, quinclorac, allylbenzylthiazide, bromonitol, iodomethyl, methyl methoxide, dimethoate, dazomet, dichloroisopropyl ether, thiamethoxam, fenpropathrin, fenpropathrin, fenpropathrin, thiophanate-methyl, thiocarbamate, thiophanate-methyl, dichloroisonicotinic acid, and allylisothiazide; the total mass percentage of compounds of formula I, Ia, and Ib in the fungicidal composition of the present invention is 1%-90%, and the mass percentage of compounds of formula I, Ia, and Ib of the present invention to the aforementioned commercial fungicides is 1%. 99% to 99% 1%; the formulation of the bactericidal composition is selected from: seed treatment emulsions, water-in-oil emulsions, microemulsions, suspensions, capsule suspensions, water-soluble granules, fine granules, soluble concentrates, poisoned grains, block poisoned bait, granular poisoned bait, flake poisoned bait, concentrated poisoned bait, slow-release blocks, electrostatic sprays, oil-in-water emulsions, smoke cans, smoke candles, smoke tubes, smoke sticks, smoke sheets, smoke pellets, gas generators, ointments, hot fogging agents, cold fogging agents, aerosols, solid / liquid mixtures, liquid / liquid mixtures, solid / solid mixtures, medicated paints, microparticles, tracking powders, oil suspensions, oil-dispersible powders, concentrated gels, pouring agents, seed coating agents, coating agents, film-forming oils, ultra-low volume liquids, vapor release agents; the plant diseases for which the bactericidal composition is applicable are selected from: rice seedling rot, asparagus Eggplant root rot, potato late blight, tobacco black shank, millet powdery mildew, grape downy mildew, lettuce downy mildew, cucumber downy mildew, cucumber anthracnose; the plants suitable for the fungicide composition are selected from: rice, wheat, barley, oats, corn, sorghum, sweet potato, potato, cassava, soybean, snow pea, broad bean, pea, mung bean, adzuki bean, cotton, silkworm, peanut, rapeseed, sesame, sunflower, beet, sugarcane, coffee, cocoa, ginseng, fritillaria, rubber, coconut, oil palm, sisal, tobacco, tomato, pepper, radish, cucumber, cabbage, celery, pickled mustard greens, beet, rapeseed, onion, garlic, watermelon, cantaloupe, honeydew melon, papaya, apple, citrus and peach trees, tea, wild vegetables, bamboo shoots, hops, pepper, banana, papaya, orchid, bonsai.

[0020] The eighth aspect of this invention provides the application of compounds of formula I, Ia, and Ib combined with antiviral agents in the control of viral diseases in agricultural, forestry, and horticultural plants. The compounds of formula I, Ia, and Ib of this invention are combined with any one or two of commercial antiviral agents to form an antiviral composition for the control of viral diseases in agricultural, forestry, and horticultural plants. The commercial antiviral agents are selected from: benzothiadiazole, thiamethoxam, isothiazamide, ribavirin, antoflavone, ningnanmycin, methamidophos, or salicylic acid, pyrimethanil, dichloroisonicotinic acid, allylisothiazide, jinggangmycin, and morpholine guanidine hydrochloride. The total mass percentage of compounds of formula I, Ia, and Ib in the antiviral composition is 1%-90%, and the ratio of compounds of formula I, Ia, and Ib of this invention to the aforementioned commercial antiviral agents is 1% by mass. 99% to 99% 1%; the formulation of the antiviral composition is selected from: seed treatment emulsions, water-in-oil emulsions, microemulsions, suspensions, capsule suspensions, water-soluble granules, fine granules, soluble concentrates, poisoned grains, block poisoned baits, granular poisoned baits, flake poisoned baits, concentrated poisoned baits, slow-release blocks, electrostatic sprays, oil-in-water emulsions, smoke cans, smoke candles, smoke tubes, smoke sticks, smoke sheets, smoke pellets, gas generators, ointments, hot fogging agents, cold fogging agents, aerosols, solid / liquid mixtures, liquid / liquid mixtures, solid / solid mixtures, medicated paints, microparticles, tracking powders, oil suspensions, oil-dispersible powders, concentrated gels, spraying agents, seed coating agents, coating agents, film-forming oils, ultra-low volume liquids, vapor release agents; the viral diseases controlled by the antiviral composition are selected from: rice dwarf virus, yellow dwarf virus, rice stripe virus, tomato Fern leaf virus disease, pepper mosaic virus disease, tobacco vein necrosis virus disease, maize dwarf mosaic virus, cauliflower mosaic virus, citrus virus disease, Cymbidium faberi leaf virus, Cymbidium faberi ringspot virus; the plants used for prevention and control of the antiviral composition are selected from: rice, wheat, barley, oats, corn, sorghum, sweet potato, potato, cassava, soybean, snow pea, broad bean, pea, mung bean, adzuki bean, cotton, silkworm, peanut, rapeseed, sesame, sunflower, beet, sugarcane, coffee, cocoa, ginseng, fritillaria, rubber, coconut, oil palm, sisal, tobacco, tomato, pepper, radish, cucumber, cabbage, celery, pickled mustard greens, beet, rapeseed, onion, garlic, watermelon, cantaloupe, honeydew melon, papaya, apple, citrus and peach trees, tea, wild vegetables, bamboo shoots, hops, pepper, banana, papaya, orchid, bonsai.

[0021] The ninth aspect of this invention provides the application of compounds of formula I, Ia, and Ib combined with acaricides in the control of mite pests in agricultural, forestry, and horticultural plants. The compounds of formula I, Ia, and Ib of this invention are combined with any one or two of commercial acaricides to form acaricide compositions for the control of mite pests in agricultural, forestry, and horticultural plants. The commercial acaricides are selected from: dichlorvos, heptamethrin, methamidophos, dibromophos, pyrimiphos, chlorpyrifos, ethion, chlorfenapyr, fenpyrophos, methyl pyrimiphos, quinalphos, abamectin, acephate, chlorpyrifos, chlorpyrifos, chlorpyrifos, chlorfenapyr, chlorpyrifos, chlorfenapyr, bifenthrin, chlorpyrifos, etc. Cypermethrin, Lambda-cyhalothrin, Cypermethrin, Flufenoxuron, Lambda-cyhalothrin, Bromoflufenoxuron, Bifenazate, Benthiocarb, Butanilox, Carbofuran, Carbofuran, Dimethoate, Benomyl, Chlorpyrifos, Butanilox, Carbofuran, Benzyl benzoate, Bromofenoxuron, Diflubenzuron, Acaricide, Flufenoxuron, Liuyangmycin, Chlorfenapyr, Bacillus thuringiensis, Acaricide, Liuyangmycin, Abamectin, Doramectin, Epranomycin, Ivermectin, Selamectin, Moxicillin, Pyrethroid, Nicotine, Matrine, Azadirachtin, Rotenone, Pyridaben, Pyridaben, Azoxystrobin, Tetramethrin, Propylthiamethoxam, Thiamethoxam, Spirodiclofen, Pyrimethanil 、 Acaricides, dicofol, and pyridaben; the total mass percentage of compounds of formula I, Ia, and Ib in the acaricide composition of this invention is 1%-90%, and the ratio of compounds of formula I, Ia, and Ib of this invention to the commercial acaricide is 1% by mass. 99% to 99% 1%; the formulation of the acaricide composition is selected from: seed treatment emulsions, water-in-oil emulsions, microemulsions, suspensions, capsule suspensions, water-soluble granules, fine granules, soluble concentrates, poisoned grains, block poisoned baits, granular poisoned baits, flake poisoned baits, concentrated poisoned baits, slow-release blocks, electrostatic sprays, oil-in-water emulsions, smoke cans, smoke candles, smoke tubes, smoke sticks, smoke sheets, smoke pellets, gas generators, ointments, hot fogging agents, cold fogging agents, aerosols, solid / liquid mixtures, liquid / liquid mixtures, solid / solid mixtures, medicated paints, microparticles, tracking powders, oil suspensions, oil-dispersible powders, concentrated gels, pouring agents, seed coating agents, smearing agents, film-forming oils, ultra-low volume liquids, vapor release agents; the mites controlled by the acaricide composition are selected from: mites from the Tetranychidae and Trichophyton families. The acaricide composition is used to control harmful mites, including those belonging to the families Erythroides, Chlorophyta, and Chlorophyta. These mites are global agricultural, forestry, horticultural, and sanitary pests. The plants used for control are selected from: rice, wheat, barley, oats, corn, sorghum, sweet potato, potato, cassava, soybean, snow pea, broad bean, pea, mung bean, adzuki bean, cotton, silkworm, peanut, rapeseed, sesame, sunflower, beet, sugarcane, coffee, cocoa, ginseng, fritillaria, rubber, coconut, oil palm, sisal, tobacco, tomato, chili pepper, radish, cucumber, cabbage, celery, pickled mustard greens, beet, rapeseed, onion, garlic, watermelon, cantaloupe, honeydew melon, papaya, apple, citrus and peach trees, tea, wild vegetables, bamboo shoots, hops, pepper, banana, papaya, orchid, and bonsai.

[0022] The tenth aspect of this invention provides the use of compounds of formula I, Ia, and Ib in the preparation of pesticide compositions. The pesticide compositions prepared by the present invention using compounds of formula I, Ia, and Ib contain the compounds of formula I, Ia, and Ib of the present invention as active ingredients, wherein the active ingredient has a mass percentage content of 0.1% to 99.9%, the solid or liquid adjuvant has a mass percentage content of 99.9% to 0.1%, and further contains, optionally, 0% to 25% by mass of a surfactant.

[0023] The eleventh aspect of this invention provides the application of compounds containing formula I, Ia, and Ib in the preparation of pesticide compound compositions. The compounds containing formula I, Ia, and Ib of this invention can be compounded with other commercial pesticides, namely insecticides, acaricides, fungicides, antiviral agents, or plant activators, to prepare pesticide compound compositions. These compound compositions contain the compounds containing formula I, Ia, and Ib of this invention and other commercial pesticides, namely insecticides, acaricides, fungicides, antiviral agents, or plant activators, as active ingredients. The ratio of the compounds containing formula I, Ia, and Ib of this invention to other commercial pesticides, namely insecticides, acaricides, fungicides, antiviral agents, or plant activators, is 1% by mass. 99% to 99% 1%, with an active ingredient content of 0.1% to 99.9% by mass, solid or liquid additives of 99.9% to 0.1% by mass, and optionally surfactants of 0% to 25% by mass.

[0024] The following is an explanation and description of the terminology used in this invention: The compounds and derivatives provided in this invention can be named according to the IUPAC (International Union of Pure and Applied Chemistry) or CAS (Chemical Abstracts Service, Columbus, OH) nomenclature system.

[0025] Regarding the definition of terms used in this invention: Unless otherwise stated, the initial definitions provided for groups or terms herein apply to the groups or terms used throughout this specification; for terms not specifically defined herein, the meanings that a person skilled in the art would give them should be given based on the disclosure and context.

[0026] "Substitution" refers to the replacement of hydrogen atoms in a molecule by other different atoms or molecules.

[0027] The minimum and maximum carbon atom content in hydrocarbon groups are indicated by prefixes. For example, the prefix Ca-b alkyl indicates any alkyl group containing "a" to "b" carbon atoms. Therefore, for example, "C1-4 alkyl" refers to an alkyl group containing 1 to 4 carbon atoms.

[0028] The term "alkyl" refers to a saturated hydrocarbon chain having a specified number of member atoms. For example, C1-6 alkyl refers to an alkyl group having 1 to 6 member atoms, such as 1 to 4 member atoms. Alkyl groups can be straight-chain or branched. Representative branched alkyl groups have one, two, or three branches. Alkyl groups may optionally be substituted by one or more substituents as defined herein. Alkyl groups include methyl, ethyl, propyl (n-propyl and isopropyl), butyl (n-butyl, isobutyl, and tert-butyl), pentyl (n-pentyl, isopentyl, and neopentyl), and hexyl, 2,2-dimethylbutyl, and 2,3-dimethylbutyl, etc. The term "C1-C3 alkyl" refers to a straight-chain or branched saturated hydrocarbon group having 1 to 3 carbon atoms. Alkyl groups may also be part of other groups, such as C1-C6 alkoxy groups.

[0029] The term "C6-C" 10 "Aryl" refers to an all-carbon monocyclic or fused polycyclic group with 6 to 10 carbon atoms and a fully conjugated π-electron system. Typical examples include, but are not limited to, phenyl, naphthyl, and biphenyl groups.

[0030] The term "heteroaryl" refers to a monocyclic or fused cyclic group containing one, two, three, or four cyclic heteroatoms selected from N, O, or S, with the remaining ring atoms being C, and possessing a fully conjugated π-electron system. The term "C5-C" 12 "Heteroaryl" refers to a heteroaryl group containing 3 to 10 carbon atoms in its ring. (C5-C) 10 Heteroaryl groups include, but are not limited to, pyrrole, furanyl, thiophene, imidazolyl, oxazolyl, thiazolyl, pyrazolyl, pyrimidinyl, pyridinyl, and isothiazolyl.

[0031] The term "halogen" refers to fluorine, chlorine, bromine, or iodine.

[0032] The term "halogenated alkyl" refers to an alkyl group in which the hydrogen atom can be replaced by one or more halogen atoms. For example, C1-4 halogenated alkyl refers to an alkyl group containing 1 to 4 carbon atoms in which the hydrogen atom is replaced by one or more halogen atoms.

[0033] Obviously, based on the above description of the present invention, and according to common technical knowledge and conventional methods in the field, various other modifications, substitutions or alterations can be made without departing from the basic technical concept of the present invention.

[0034] Beneficial technical effects of the present invention: 1. The compounds of this invention are based on the core bi-heterocyclic skeleton of the potential pyruvate kinase inhibitor 1,3,4-oxadiazole-thiazolium. By combining the ring-opening strategy, a series of thiazole-containing diamide derivatives were designed and derived. Based on the structure-activity relationship found in the experiment, the design and synthesis of target compounds with better bactericidal activity were guided. Finally, a class of thiazole-containing diamide derivatives were obtained, and their biological activities were systematically screened and evaluated.

[0035] 2. The compounds of the present invention, formulas Ib, If, Ih, Ij, Ik, In, Io, Ir, and Is, exhibit high bactericidal activity. Attached Figure Description

[0036] Figure 1 Compound gw-34 has an EC50 effect on Rhizoctonia solani. 50 Test results. Detailed Implementation

[0037] The present invention is further illustrated by the following examples, but these are not intended to limit the invention.

[0038] Intermediate Example 1: Preparation of Compound I-2a Add 12 mmol of thiocarbamate to a 200 mL round-bottom flask, dissolved in 40 mL of anhydrous ethanol. Add 10 mmol of 1-cyclopropyl-2-bromoethylone I-1a dropwise with stirring at room temperature. After the addition is complete, transfer the reaction mixture to an oil bath and heat to 80 °C. Reflux for 2–4 h, monitoring the reaction by TLC. After the reaction is complete, remove the solvent by rotary evaporation, dissolve the residue in ethyl acetate, wash twice with saturated sodium chloride solution, and dry the organic layer with anhydrous sodium sulfate. After vacuum filtration, reflux the residue with petroleum ether / ethyl acetate (3:1–5:1) with a boiling range of 60–90 °C. yes / yes Using 100-200 mesh silica gel column chromatography as the eluent, intermediate I-2a was obtained.

[0039] Intermediate Example 1: Preparation of Compound I-3a Compound I-2a (10 mmol) was added to a 200 mL round-bottom flask and dissolved in 40 mL of anhydrous ethanol. 80% hydrazine hydrate (12 mmol) was added dropwise while stirring at room temperature. After the addition was complete, the reaction system was transferred to an oil bath and heated to 80 °C. The reaction was refluxed for 2-4 h and monitored by TLC. After the reaction was complete, it was cooled to room temperature and the reaction was stirred for another 1-2 h to obtain a large amount of solid. The solid intermediate I-3a was obtained by vacuum filtration.

[0040] Example 1: Preparation of compound gw-34 Intermediate I-3a (2.0 mmol), 2-chloronicotinyl chloride (2.0 mmol), triethylamine (2.2 mmol), and 20 mL of dichlorophenoxyacetic acid were added to a 50 mL round-bottom flask and reacted at room temperature for 4 hours. After the reaction was complete, the mixture was extracted twice with saturated sodium bicarbonate solution (50 mL × 2), followed by extraction twice with dichloromethane (50 mL × 2). The combined organic layers were washed twice with saturated sodium chloride solution and dried over anhydrous sodium sulfate. The residue was filtered under reduced pressure and then treated with petroleum ether / ethyl acetate (1:1 to 3:1) with a boiling range of 60–90 °C. yes / yes Using 100-200 mesh silica gel column chromatography as the eluent, the target compound gw-34 was purified as a white solid with a yield of 52%.

[0041] 1 H NMR (500 MHz, DMSO) δ 10.81 (s, 1H), 10.69 (s, 1H), 8.56 (dd, J =4.8, 1.9 Hz, 1H), 7.95 (dd, J = 7.5, 1.9 Hz, 1H), 7.69 (s, 1H), 7.58 (ddd, J=7.4, 4.8, 2.6 Hz, 1H), 2.18 (tt, J = 7.9, 5.3 Hz, 1H), 1.03 – 0.92 (m, 4H). 13 CNMR (126 MHz, DMSO) δ 164.71 (s), 160.83 (s), 160.48 (s), 158.84 (s), 151.51 (s), 147.43 (s), 139.09 (s), 131.26 (s), 123.60 (s), 118.39 (s), 12.36 (s), 8.90 (s). Example 2: Preparation of compound gw-36 Compound gw-36 was prepared using a similar preparation method to that used in intermediates Examples 1-2 and Example 1. 1 H NMR(500 MHz, DMSO) δ 10.62 (s, 2H), 7.68 (s, 1H), 7.58 – 7.49 (m, 3H), 7.50 –7.44 (m, 1H), 2.24 – 2.11 (m, 1H), 0.95 (t, J = 16.3 Hz, 4H). 13 C NMR (126 MHz, DMSO) δ 165.89 (s), 161.07 (s), 160.42 (s), 158.85 (s), 134.91 (s), 132.06 (s), 130.96 (s), 130.42 (s), 129.86 (s), 127.65 (s), 118.26 (s), 12.36 (s), 8.89 (s). Example 3: Preparation of compound gw-38 Compound GW-38 was prepared using a similar preparation method to that used in intermediates Examples 1-2 and Example 1. 1 H NMR (500 MHz, DMSO) δ 10.74 (s, 1H), 10.56 (s, 1H), 7.76 (d, J = 1.9 Hz, 1H), 7.68(s, 1H), 7.61 – 7.56 (m, 1H), 7.53 (d, J = 8.2 Hz, 1H), 2.17 (tt, J = 8.0, 5.2Hz, 1H), 1.00 – 0.93 (m, 4H).13 C NMR (126 MHz, DMSO) δ 165.10 (s), 160.90 (s), 160.46 (s), 158.86 (s), 135.88 (s), 133.72 (s), 132.26 (s), 131.19 (s), 130.03 (s), 127.95 (s), 118.34 (s), 12.35 (s), 8.88 (s). Example 4: Preparation of compound gw-39 Compound GW-39 was prepared using a similar preparation method to that used in intermediates Examples 1-2 and Example 1. 1 H NMR (500 MHz, DMSO) δ 10.85 (s, 1H), 10.80 (s, 1H), 7.68 (s, 1H), 7.55 (t, J = 2.5Hz, 1H), 7.54 (s, 1H), 7.49 (dd, J = 9.2, 6.7 Hz, 1H), 2.17 (dq, J = 13.2, 6.6Hz, 1H), 0.97 (d, J = 6.6 Hz, 4H). 13 C NMR (126 MHz, DMSO) δ 162.95 (s), 161.09 (s), 160.41 (s), 158.61 (s), 134.93 (s), 132.31 (s), 132.16 (s), 128.71 (s), 118.30 (s), 12.40 (s), 8.92 (s). Example 5: Preparation of compound gw-41 Compound GW-41 was prepared using a similar preparation method to that used in intermediates Examples 1-2 and Example 1. 1 H NMR(500 MHz, DMSO) δ 10.61 (s, 1H), 10.26 (s, 1H), 7.67 (s, 1H), 7.43 – 7.36 (m,2H), 7.29 (t, J = 8.4 Hz, 2H), 2.42 (d, J = 8.3 Hz, 3H), 2.17 (tt, J = 8.0, 5.2Hz, 1H), 0.96 (tt, J= 4.3, 2.2 Hz, 4H). 13 C NMR (126 MHz, DMSO) δ 168.67 (s),161.19 (s), 160.41 (s), 159.00 (s), 136.39 (s), 135.20 (s), 131.04 (s),130.42 (s), 127.79 (s), 126.03 (s), 118.23 (s), 19.75 (s), 12.36 (s), 8.87 (s). Example 6: Preparation of compound gw-42 Compound GW-42 was prepared using a similar preparation method to that used in intermediates Examples 1-2 and Example 1. 1 H NMR (500 MHz, DMSO) δ 10.76 (s, 1H), 10.58 (s, 1H), 7.85 (d, J = 7.7 Hz, 1H), 7.81(t, J = 7.4 Hz, 1H), 7.73 (t, J = 7.5 Hz, 1H), 7.68 (s, 2H), 2.23 – 2.10 (m,1H), 0.97 (d, J = 8.1 Hz, 4H). 13 C NMR (126 MHz, DMSO) δ 166.67 (s), 161.01 (s), 160.45 (s), 158.96 (s), 134.39 (s), 132.97 (s), 131.06 (s), 129.65 (s), 127.04 (q, J = 31.8 Hz), 126.98 (d, J = 4.8 Hz), 124.00 (d, J = 273.8 Hz),118.29 (s), 12.36 (s), 8.88 (s). Example 7: Preparation of compound gw-43 Compound GW-43 was prepared using a similar preparation method to that used in intermediates Examples 1-2 and Example 1. 1 H NMR (500 MHz, DMSO) δ 10.72 (s, 1H), 10.43 (s, 1H), 7.71 – 7.64 (m, 2H), 7.60 (tdd, J= 7.2, 5.3, 1.7 Hz, 1H), 7.35 (ddd, J = 9.9, 7.2, 6.1 Hz, 2H), 2.18(ddd, J = 7.8, 6.4, 3.9 Hz, 1H), 0.96 (dq, J = 3.4, 2.2 Hz, 4H). 13 C NMR (126MHz, DMSO) δ 163.75 (s), 161.04 (s), 160.45 (s), 159.74 (d, J = 250.8 Hz),158.91 (s), 133.64 (d, J = 8.4 Hz), 130.62 (d, J = 2.6 Hz), 125.07 (d, J = 3.1Hz), 122.55 (d, J = 14.6 Hz), 118.26 (s), 116.81 (d, J = 21.4 Hz), 12.36 (s), 8.89 (s). Example 8: Preparation of compound gw-45 Compound GW-45 was prepared using a similar preparation method to that used in intermediates Examples 1-2 and Example 1. 1 H NMR (500 MHz, DMSO) δ 11.01 (s, 1H), 10.96 (s, 1H), 7.70 (s, 1H), 2.19 (dq, J =8.2, 5.0 Hz, 1H), 1.02 – 0.86 (m, 4H). 13 C NMR (126 MHz, DMSO) δ 160.60 (s),160.48 (s), 158.76 (s), 157.31 (s), 153.95 (s), 148.68 (s), 122.12 (s),118.60 (s), 12.34 (s), 8.91 (s). Example 9: Preparation of compound gw-48 Compound GW-48 was prepared using a similar preparation method to that used in intermediates Examples 1-2 and Example 1. 1H NMR (500 MHz, DMSO) δ 11.22 (s, 1H), 10.94 (s, 1H), 8.90 (s, 1H), 8.56 (dd, J =4.8, 1.9 Hz, 1H), 7.96 (dd, J = 7.5, 1.9 Hz, 1H), 7.58 (dd, J = 7.5, 4.8 Hz, 1H). 13 C NMR (126 MHz, DMSO) δ 164.87 (s), 164.58 (s), 157.96 (s), 151.56 (s), 147.44 (s), 143.97 (q, J = 37.5 Hz), 139.09 (s), 131.11 (s), 129.66 (s), 123.60 (s), 120.57 (q, J = 270.8 Hz). Example 10: Preparation of compound YTF-1 Compound YTF-1 was prepared using a similar preparation method to that used in intermediates Examples 1-2 and Example 1. 1 H NMR(500 MHz, DMSO) δ 11.09 (s, 1H), 10.81 (s, 1H), 8.59 – 8.55 (m, 1H), 8.51 (s,1H), 8.13 (dd, J = 7.6, 1.9 Hz, 1H), 8.00 – 7.95 (m, 1H), 7.63 (dd, J = 7.8, 1.4 Hz, 1H), 7.59 (dt, J = 8.3, 4.2 Hz, 1H), 7.53 – 7.44 (m, 2H). 13 C NMR (126MHz, DMSO) δ 164.70 (s), 161.02 (s), 158.75 (s), 152.50 (s), 151.54 (s), 147.45 (s), 139.11 (s), 132.54 (s), 132.36 (s), 131.63 (s), 131.25 (s), 130.86 (s), 130.69 (s), 127.92 (s), 125.33 (s), 123.61 (s). Example 11: Preparation of compound YTF-2 Compound YTF-2 was prepared using a similar preparation method to that used in intermediates Examples 1-2 and Example 1. 1 H NMR (500 MHz, DMSO) δ 10.84 (s, 2H), 8.40 (s, 1H), 8.03 (d, J = 6.7 Hz, 1H), 7.88 (d, J = 11.5 Hz, 1H), 7.81 (d, J = 4.9 Hz, 1H), 7.65 – 7.57 (m, 1H), 7.52 –7.37 (m, 2H), 7.24 – 7.17 (m, 1H). 13 C NMR (126 MHz, DMSO) δ 160.64 (s), 158.14 (s), 152.42 (s), 138.46 (s), 132.79 (s), 132.38 (s), 131.66 (s), 131.54 (s), 130.75 (s), 130.56 (s), 129.19 (s), 128.53 (s), 127.85 (s), 124.60 (s), 124.55 (s). Example 12: Preparation of compound YTF-3 Compound YTF-3 was prepared using a similar preparation method to that used in intermediates Examples 1-2 and Example 1. 1 H NMR (500 MHz, DMSO) δ 11.04 (s, 1H), 10.59 (s, 1H), 8.51 (s, 1H), 8.14 (dd, J =7.6, 1.9 Hz, 1H), 7.63 (dd, J = 7.8, 1.4 Hz, 1H), 7.59 – 7.53 (m, 3H), 7.53 –7.50 (m, 1H), 7.48 (ddd, J = 7.2, 4.1, 1.5 Hz, 2H). 13C NMR (126 MHz, DMSO) δ165.91 (s), 161.17 (s), 158.81 (s), 152.44 (s), 134.85 (s), 132.54 (s), 132.37 (s), 132.11 (s), 131.61 (s), 130.97 (s), 130.87 (s), 130.68 (s), 130.45 (s), 129.88 (s), 127.92 (s), 127.68 (s), 125.26 (s). Example 13: Preparation of compound YTF-4 Compound YTF-4 was prepared using a similar preparation method to that used in intermediates Examples 1-2 and Example 1. 1 H NMR (500 MHz, DMSO) δ 11.08 (s, 1H), 10.69 (s, 1H), 8.51 (s, 1H), 8.13 (dd, J =7.6, 1.7 Hz, 1H), 7.77 (d, J = 1.7 Hz, 1H), 7.61 (ddd, J = 10.1, 8.0, 1.4 Hz,2H), 7.57 (d, J = 8.2 Hz, 1H), 7.53 – 7.45 (m, 2H). 13 C NMR (126 MHz, DMSO) δ165.13 (s), 161.05 (s), 158.81 (s), 152.49 (s), 135.94 (s), 133.65 (s), 132.53 (s), 132.35 (s), 132.28 (s), 131.62 (s), 131.21 (s), 130.86 (s), 130.69 (s), 130.05 (s), 127.98 (s), 127.92 (s), 125.31 (s). Example 14: Preparation of compound YTF-5 Compound YTF-5 was prepared using a similar preparation method to that used in intermediates Examples 1-2 and Example 1. 1 H NMR (500 MHz, DMSO) δ 11.17 (s, 1H), 10.90 (s, 1H), 8.52 (s, 1H), 8.18 (dd, J=7.6, 1.8 Hz, 1H), 7.63 (dd, J = 7.8, 1.3 Hz, 1H), 7.58 – 7.53 (m, 3H), 7.53 –7.45 (m, 3H). 13 C NMR (126 MHz, DMSO) δ 165.83 (s), 162.95 (s), 161.21 (s), 158.53 (s), 152.38 (s), 135.12 (s), 134.91 (s), 132.53 (s), 132.43 (s),132.30 (s), 132.20 (s), 131.88 (s), 131.56 (s), 130.87 (s), 130.65 (s), 130.42 (s), 128.73 (s), 128.68 (s), 127.89 (s), 125.23(s). Example 15: Preparation of compound YTF-7 Compound YTF-7 was prepared using a similar preparation method to that used in intermediates Examples 1-2 and Example 1. 1 H NMR (500 MHz, DMSO) δ 10.89 (s, 1H), 10.38 (s, 1H), 8.49 (s, 1H), 8.11 (dd, J =7.6, 1.6 Hz, 1H), 7.63 (dd, J = 7.8, 1.3 Hz, 1H), 7.49 (dtd, J = 17.0, 7.4, 1.5Hz, 2H), 7.45 – 7.38 (m, 2H), 7.30 (t, J = 8.2 Hz, 2H), 2.44 (s, 3H). 13 C NMR (126 MHz, DMSO) δ 168.87 (s), 168.57 (s), 158.89 (s), 152.44 (s), 136.42 (s), 135.18 (s), 132.62 (s), 132.36 (s), 131.64 (s), 131.07 (s), 130.85 (s), 130.66 (s), 130.45 (s), 127.91 (s), 127.82 (s), 126.05 (s), 125.12 (s), 19.78(s). Example 16: Preparation of compound YTF-12 Compound YTF-12 was prepared using a similar preparation method to that used in intermediates Examples 1-2 and Example 1. 1 HNMR (500 MHz, DMSO) δ 11.13 (s, 1H), 10.84 (s, 1H), 8.58 (dd, J = 4.8, 1.9 Hz,1H), 8.54 (s, 1H), 8.20 – 8.13 (m, 2H), 8.00 (dd, J = 7.5, 1.9 Hz, 1H), 7.61(dd, J = 7.5, 4.8 Hz, 1H), 7.52 (t, J = 7.6 Hz, 2H), 7.43 (t, J = 7.4 Hz, 1H). 13 CNMR (126 MHz, DMSO) δ 164.80 (s), 161.54 (s), 158.83 (s), 156.09 (s), 151.57(s), 147.45 (s), 139.12 (s), 133.82 (s), 131.25 (s), 129.36 (s), 129.19 (s), 126.83 (s), 123.65 (s), 120.46 (s). Example 17: Preparation of compound YTF-13 Compound YTF-13 was prepared using a similar preparation method to that used in intermediates Examples 1-2 and Example 1. 1 HNMR (500 MHz, DMSO) δ 11.13 (s, 1H), 10.97 (s, 1H), 8.76 (s, 1H), 8.67 (s,1H), 8.59 (dt, J = 6.8, 3.4 Hz, 1H), 8.30 (dd, J = 8.6, 1.7 Hz, 1H), 8.07 (d, J = 8.6 Hz, 1H), 8.03 (dd, J = 7.5, 1.9 Hz, 1H), 8.00 (dd, J = 12.0, 5.7 Hz, 2H),7.65 – 7.62 (m, 1H), 7.59 (ddd, J= 8.1, 5.2, 1.7 Hz, 2H). 13 C NMR (126 MHz, DMSO) δ 164.84 (s), 161.72 (s), 158.85 (s), 156.03 (s), 151.57 (s), 147.48 (s), 139.15 (s), 133.59 (s), 133.42 (s), 131.32 (s), 131.29 (s), 128.97 (s),128.62 (s), 128.25 (s), 127.27 (s), 127.05 (s), 125.78 (s), 124.78 (s),123.66 (s), 120.92 (s). Example 18: Preparation of compound YTF-15 Compound YTF-15 was prepared using a similar preparation method to that used in intermediates Examples 1-2 and Example 1. 1 HNMR (500 MHz, DMSO) δ 11.15 (s, 1H), 10.66 (s, 1H), 8.76 (s, 1H), 8.66 (s,1H), 8.29 (dd, J = 8.6, 1.7 Hz, 1H), 8.06 (d, J = 8.6 Hz, 1H), 7.98 (d, J = 8.1Hz, 2H), 7.63 – 7.53 (m, 5H), 7.51 (td, J = 7.3, 1.2 Hz, 1H). 13 C NMR (126 MHz, DMSO) δ 166.05 (s), 161.84 (s), 158.90 (s), 155.99 (s), 134.88 (s), 133.59 (s), 133.42 (s), 132.15 (s), 131.34 (s), 130.99 (s), 130.47 (s), 129.90 (s),128.96 (s), 128.61 (s), 128.25 (s), 127.72 (s), 127.27 (s), 127.04 (s),125.78 (s), 124.78 (s), 120.84 (s). Example 19: Preparation of compound ZP-12 Compound ZP-12 was prepared using a similar preparation method to that used in intermediates Examples 1-2 and Example 1. 1 H NMR (500 MHz, DMSO) δ 10.73 (s, 2H), 8.47 (s, 1H), 8.19 – 8.12 (m, 2H), 7.58 (d, J = 9.1 Hz, 2H), 7.56 (s, 3H), 7.51 (dd, J = 9.1, 6.8 Hz, 1H). 13 C NMR (126 MHz, DMSO) δ 167.93 (s), 162.92 (s), 159.72 (s), 149.26 (s), 135.10 (s), 132.93 (s), 132.34 (s), 132.11 (s), 131.34 (s), 129.72 (s), 128.71 (s), 127.06 (s), 125.85 (s). Example 20: Preparation of compound ZP-13 Compound ZP-13 was prepared using a similar preparation method to that used in intermediates Examples 1-2 and Example 1. 1 H NMR (500 MHz, DMSO) δ 10.66 (s, 1H), 10.54 (d, J = 19.7 Hz, 1H), 8.48 (d, J = 12.0Hz, 1H), 8.13 (t, J = 14.4 Hz, 2H), 7.57 (s, 5H), 7.54 – 7.45 (m, 2H). 13 C NMR (126 MHz, DMSO) δ 167.95 (s), 166.00 (s), 160.09 (s), 149.23 (s), 135.06 (s), 132.91 (s), 132.02 (s), 131.35 (s), 130.99 (s), 130.42 (s), 129.92 (s), 129.75 (s), 127.65 (s), 127.03 (s), 125.85 (s). Example 21: Preparation of compound ZP-14 Compound ZP-14 was prepared using a similar preparation method to that used in intermediates Examples 1-2 and Example 1. 1H NMR (500 MHz, DMSO) δ 10.69 (s, 1H), 10.60 (s, 1H), 8.47 (s, 1H), 8.14 (dd, J =7.3, 2.1 Hz, 2H), 7.77 (t, J = 3.3 Hz, 1H), 7.60 (d, J = 1.9 Hz, 2H), 7.57 (dd, J = 8.6, 3.0 Hz, 3H). 13 C NMR (126 MHz, DMSO) δ 167.99 (s), 165.19 (s), 160.07 (s), 149.13 (s), 135.83 (s), 133.90 (s), 132.89 (s), 132.29 (s), 131.35 (s),131.25 (s), 130.03 (s), 129.74 (s), 127.95 (s), 127.02 (s), 125.94 (s). Example 22: Preparation of compound ZP-15 Compound ZP-15 was prepared using a similar preparation method to that used in intermediates Examples 1-2 and Example 1. 1 H NMR(500 MHz, DMSO) δ 10.84 (s, 1H), 10.72 (s, 1H), 8.47 (s, 1H), 8.18 – 8.13 (m,2H), 7.58 (d, J = 4.7 Hz, 2H), 7.56 (d, J = 2.0 Hz, 3H), 7.51 (dd, J = 9.1, 6.8Hz, 1H). 13 C NMR (126 MHz, DMSO) δ 167.93 (s), 162.92 (s), 159.72 (s), 149.26(s), 135.10 (s), 132.93 (s), 132.34 (s), 132.11 (s), 131.34 (s), 129.72 (s), 128.71 (s), 127.06 (s), 125.85 (s). Example 23: Preparation of compound ZP-18 Compound ZP-18 was prepared using a similar preparation method to that used in intermediates Examples 1-2 and Example 1.13 C NMR (126 MHz, DMSO) δ 167.98 (s), 166.80 (d, J = 6.8 Hz), 160.17 (s), 149.25 (s), 134.64 (s), 134.63 (s), 132.97 (s), 132.91 (s), 131.33 (s), 131.01 (s), 129.73 (s), 127.06 (q, J = 31.4 Hz), 127.03 (s), 126.96 (s), 125.88 (s), 124.06 (q, J = 273.9 Hz). Example 24: Preparation of compound ZP-20 Compound ZP-20 was prepared using a similar preparation method to that used in intermediates Examples 1-2 and Example 1. 1 H NMR (500 MHz, DMSO) δ 11.06 (d, J = 106.6 Hz, 1H), 10.85 (s, 1H), 8.50 (d, J = 4.5Hz, 1H), 8.17 – 8.07 (m, 2H), 7.61 – 7.51 (m, 3H). 13 C NMR (126 MHz, DMSO) δ168.14 (s), 159.91 (s), 157.35 (s), 154.22 (s), 148.77 (s), 148.65 (s), 132.81 (s), 131.40 (s), 129.76 (s), 127.02 (s), 126.34 (s), 122.03 (s). Example 1 The bactericidal or bacteriostatic activity of the thiazole diamide compound of formula I in this invention is determined by the mycelial growth rate method. The mycelial growth rate method is a bactericidal toxicity determination method that uses the growth rate of pathogenic fungal hyphae on a culture medium containing different concentrations of the agent to determine the bactericidal and bacteriostatic abilities of the agent. The specific steps are as follows: (1) Preparation of drug-loaded plates. Take 10 mg of the test compound and use 400 μL of... N , NDissolve the reagent in dimethylformamide and bring the volume to 20 mL with a sterile aqueous solution containing 0.1% Tween 80 emulsifier, obtaining a test reagent solution with a concentration of 500 μg / mL. Prepare the culture medium containing the reagent in a laminar flow hood. Pipette 4 mL of the test reagent solution into a sterile 50 mL centrifuge tube, add 36 mL of potato dextrose agar (PDA) medium, mix well, pour into sterile petri dishes, and after cooling, obtain a culture medium plate containing 50 μg / mL of the test reagent. Add the appropriate volume... N , N - Dimethylformamide and PDA medium containing 0.1% Tween 80 in sterile water were used as controls.

[0042] (2) Prepare the mycelium. Inoculate the long-term stored mycelium onto drug-free PDA medium and activate it 1-2 times. After the mycelium grows well, use a 4 mm diameter punch to cut the mycelium at the outer 1 / 3 of the colony.

[0043] (3) Inoculation of mycelial cakes. Use an inoculation needle to transfer the mycelial cakes to the center of the drug-coated plate, with the aerial mycelial side facing down. After sealing with sealing film, place the plate in an inverted incubator at a constant temperature of 24±1℃. Each treatment is replicated 3 times.

[0044] (4) Data collection. When the colonies of the blank control were close to the edge of the petri dish, the colony diameter was measured twice using the "cross-cross method", and the average value was used to represent the colony size.

[0045] (5) Data Analysis. Substitute the data into the growth rate calculation formula to calculate the mycelial growth inhibition rate of different compounds. The tested strains represent most of the typical plant pathogens actually occurring in the field in my country's agricultural production; their codes and names are as follows: As The Latin name of the tomato early blight pathogen is: Alternaria solani , Bc The fungus causing gray mold in cucumbers has the Latin name: Botrytis cinerea , Ca The fungus causing brown spot in peanuts has the Latin name: Cercospora arachidicola , Fg Fusarium graminearum, the causal agent of the disease, has the Latin name: Fusarium gramineae , Pp Apple ring rot fungus, its Latin name is: Physalospora piricola , Rs. The fungus causing rice sheath blight has the Latin name: Rhizoctonia solani Ss: Sclerotinia sclerotiorum, the causal agent of rapeseed disease, has the Latin name: Sclerotinia sclerotiorum Fusarium scutellatus, Fusarium oxysporum ( F. o ) and Fusarium pseudoverticum, Fusarium verticillium ( F. v ) 。

[0046] The formula for calculating the mycelial growth inhibition rate is as follows: ; Table 1. Antibacterial activity of the thiazole-containing diamide compound of formula I of the present invention (inhibition rate at 50 μg / mL / %) ; Note: The pathogen causing early blight of tomatoes. A. solani ( A. s Botrytis cinerea, B. cinerea ( B. c Peanut brown spot pathogen, C. arachidicola ( C. a Fusarium graminearum, F. graminearum ( F. g Apple ring rot pathogen, P. piricola ( P. p ); Table 2. Antibacterial activity of the thiazole-containing diamide compound of formula I of the present invention (inhibition rate at 50 μg / mL / %) ; Rhizoctonia solani, R. solani ( R.s ); Sclerotium sclerotiorum, S. sclerotiorum ( S. s Fusarium scutellatus, Fusarium oxysporum ( F. o ); Fusarium pseudoverticum, Fusarium verticillium ( F. v ).

[0047] Commercially available agents thifluzamide and triamcinolone were used as positive controls. Table 1-2 shows the in vitro bactericidal activity at a concentration of 50 μg / mL, indicating that the target compound in this invention exhibits a certain degree of in vitro bactericidal activity against all nine tested pathogenic fungi. Compound ZP-15... A. solani The inhibition rate was 66.7%, showing antibacterial activity comparable to thifluzamide (67.2%).

[0048] Compounds gw-39, gw-43, gw-45, ytf-3, ytf-5, ytf-7 and zp-15 pairs B. cinerea The inhibition rates ranged from 64.0% to 94.6%, all superior to thifluzamide (32.4%). Compound gw-45 showed an inhibition rate of 94.6%, comparable to that of triamcinolone (96.1%). Compounds gw-34 and gw-36 showed inhibition rates against... R. solani The inhibitory activity was 100% for both, demonstrating superior inhibitory activity compared to triamcinolone (95.3%) and thifluzamide (90.2%). (See attached diagram in the product manual.) Figure 1 Compound GW-45 is effective against...S. sclerotia The inhibition rate was 80.7%, which was better than that of thifluzamide (15.2%).

[0049] In summary, compounds ZP-15, GW-34, GW-36, GW-39, GW-43, GW-45, YTF-3, YTF-5, and YTF-7 exhibited good bactericidal activity.

[0050] The above description is merely a preferred embodiment of the present invention, but the scope of protection of the present invention is not limited thereto. Any variations or substitutions that can be easily conceived by those skilled in the art within the technical scope disclosed in the present invention should be included within the scope of protection of the present invention. Therefore, the scope of protection of the present invention should be determined by the scope of the claims.

Claims

1. The compound represented by Formula I, or its stereoisomers, or its agriculturally acceptable salts: ； Formula I; in, R1 is selected from C1-C6 straight-chain or branched alkyl groups, halogen-substituted C1-C6 straight-chain or branched alkyl groups, C3-C6 cycloalkyl groups, and C6-C6 cycloalkyl groups. 12 Aryl groups or C5-C groups containing N, O, or S atoms 12 heteroaryl; the C5-C 12 Aryl groups or C6-C groups containing N, O, or S atoms 12 The heteroaryl group can be further optionally influenced by one, two, or three independent R groups. 1a replace, R 1a Selected from hydrogen, halogens, or C1-C6 straight-chain or branched alkyl groups; R2 is selected from C6-C 12 Aryl groups or C5-C groups containing N, O, or S atoms 12 heteroaryl; the C6-C 12 Aryl, C5-C 12 Aryl groups or C5-C groups containing N, O, or S atoms 12 The heteroaryl group can be further optionally influenced by one, two, or three independent R groups. 2a replace; R 2a Selected from hydrogen, halogen, halogen-substituted C1-C6 straight-chain or branched alkyl groups or C1-C6 straight-chain or branched alkyl groups.

2. The compound, or its stereoisomer, or its agriculturally acceptable salt according to claim 1, characterized in that: The compound of formula I is selected from the following structures. or ; Formula Ia and Formula Ib.

3. The compound, or its stereoisomer, or its agriculturally acceptable salt according to claims 1-2, characterized in that: R1 is selected from cyclopropyl, trifluoromethyl, phenyl, or naphthyl; the phenyl or naphthyl group may further optionally be replaced by one, two, or three independent R1 groups. 1a replace, R 1a Selected from halogens; And / or, R2 is selected from phenyl, pyridyl, isothiazolyl, or thiophene; said phenyl, pyridyl, isothiazolyl, or thiophene The base can be further optionally assigned to one, two, or three independent R. 2a replace; R 2a Selected from halogens, halogen-substituted C1-C6 straight-chain or branched alkyl groups, or C1-C6 straight-chain or branched alkyl groups.

4. The compound according to claims 1-2, or its stereoisomer, or its agriculturally chemically acceptable salt. Its features are: R1 is selected from -CF3 , or ; R2 is selected from , , , , , , , , or .

5. The compound according to any one of claims 1-3, or its stereoisomer, or its agriculturally chemically acceptable salt, characterized in that: The compound described in Formula I is specifically: 。 6. A pesticide composition comprising at least one compound of Formula I according to any one of claims 1-5, or a stereoisomer thereof, or an agriculturally chemically acceptable salt thereof, and a carrier; said carrier being in liquid or solid form.

7. The application of the compound of formula I, or its stereoisomer, or its agrochemically acceptable salt, or the pesticide composition of claim 6, in the control of plant fungal diseases, preferably wherein the plant fungal disease is a pathogen causing early blight of tomato, Botrytis cinerea, brown spot of peanut, Fusarium graminearum, ring rot of apple, Rhizoctonia solani, Fusarium oxysporum, Fusarium verticillata, or Sclerotinia sclerotiorum.

8. A bactericide, characterized in that, The disinfectant contains a bactericidal effective amount of at least one of the compounds of formula I according to any one of claims 1-5, or a stereoisomer thereof, or an agriculturally chemically acceptable salt thereof, and optionally contains excipients.

9. The bactericide according to claim 8, characterized in that, The formulation of the bactericide is selected from at least one of emulsifiable concentrate, suspension concentrate, wettable powder, powder, granule, aqueous solution, mother liquor, and masterbatch.

10. A method for controlling or preventing the infection of useful plants by plant pathogenic microorganisms, wherein a fungicide effective amount of a compound having formula I according to any one of claims 1 to 5, or a composition containing such compound as an active ingredient, is applied to said plant, its parts, or its location.

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