CN112358474A - Difluoropyrazole thiazole methanamide derivatives and preparation method and application thereof - Google Patents
Difluoropyrazole thiazole methanamide derivatives and preparation method and application thereof Download PDFInfo
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- CN112358474A CN112358474A CN202011199735.3A CN202011199735A CN112358474A CN 112358474 A CN112358474 A CN 112358474A CN 202011199735 A CN202011199735 A CN 202011199735A CN 112358474 A CN112358474 A CN 112358474A
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
- C07D417/04—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings directly linked by a ring-member-to-ring-member bond
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- A—HUMAN NECESSITIES
- A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
- A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
- A01N43/00—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds
- A01N43/72—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with nitrogen atoms and oxygen or sulfur atoms as ring hetero atoms
- A01N43/74—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with nitrogen atoms and oxygen or sulfur atoms as ring hetero atoms five-membered rings with one nitrogen atom and either one oxygen atom or one sulfur atom in positions 1,3
- A01N43/78—1,3-Thiazoles; Hydrogenated 1,3-thiazoles
Abstract
The invention provides difluoropyrazole thiazole formamide derivatives, and a preparation method and application thereof, and particularly relates to difluoropyrazole thiazole formamide derivatives, wherein the chemical structure general formula of the difluoropyrazole thiazole formamide derivatives is shown as formula I:
Description
Technical Field
The technical scheme of the invention relates to a difluoro pyrazole formamide compound containing thiazole, in particular to an N-phenethyl thiazole-4-formamide derivative.
Background
Thiazole is a five-membered heterocyclic compound containing nitrogen and sulfur atoms, and thiazole derivatives have wide application and development prospects in a plurality of fields such as medicines, pesticides, materials, biological coloring agents, supermolecule chemistry and the like.
Fungicides such as succinate dehydrogenase inhibitors have been known for over 50 years; carboxin developed by the american co-venture company was successfully marketed in 1966 earlier than triazoles and strobilurins, and until 2009, the action committee on fungicide resistance classified such fungicides alone according to their mechanism of action, due to their action on succinate dehydrogenase of the mitochondrial respiratory system of pathogenic bacteria.
Since the carboxin was reported in 1966, succinate dehydrogenase inhibitor bactericides have undergone three generations of succession, the biological activity is improved, the bactericidal spectrum is expanded, the compounds can be used for preventing and treating various diseases on a plurality of crops, and the compounds become a very important bactericide variety in the production (Zhang Yibin, world pesticide, 2007, 29 (1): 1-7); among them, boscalid marketed in 2003 is an important milestone in the development history of succinate dehydrogenase inhibitor bactericides, and is a first truly broad-spectrum succinate dehydrogenase inhibitor bactericide (facial courage, et al, pesticides, 2008, 47 (2): 132-plus 135), thereby attracting numerous companies to review the products and invest energy and financial resources in the field to create new pesticides.
Because SDHIs bactericides have single action sites and pay attention to resistance risks, FRAC classifies the SDHIs bactericides as medium-to-high resistance risk medicaments, resistance researches on the SDHIs bactericides have more reports, field or indoor resistant strains are obtained in many germs, but the main related varieties are carboxin and boscalid (Liliang, et al. pesticides 2011, 50 (3): 165-169).
In order to find and discover pesticide lead and candidate compounds with higher efficiency, broad spectrum, low toxicity and no cross resistance, the invention introduces thiazole into the lead structure of difluoropyrazole formamide, designs and synthesizes difluoropyrazole thiazole formamide derivatives, and screens and evaluates the biological activity of the system.
Disclosure of Invention
The technical problem to be solved by the invention is as follows: provides a synthesis method of novel difluoropyrazole thiazole formamide derivatives, provides a method for regulating and controlling the biological activity of agricultural, horticultural and sanitary and forestry plant pests and plant pathogens by using the compounds and a determination method thereof, and also provides applications of the compounds in the agricultural field, the horticultural field, the forestry field and the sanitary field.
The technical scheme adopted by the invention for solving the technical problem is as follows: the chemical structural general formula of the difluoropyrazole thiazole methanamide compound with insecticidal, acaricidal activity, bactericidal activity, plant virus resistance activity and plant disease resistance induction activity in the agricultural field, the horticultural field and the forestry field is shown as I:
wherein Het is selected from: thiazol-2, 4-yl, thiazol-4, 2-yl; r is selected from: phenyl, 2-chlorophenyl, 4-chlorophenyl, 2, 4-dichlorophenyl, 4-fluorophenyl, 4-methylphenyl, 4-trifluoromethylphenyl, 4-trifluoromethoxyphenyl; n is 2 to 4.
The synthetic route of the difluoropyrazole thiazole methanamide derivative I and the intermediate thereof is as follows:
synthetic route of intermediate 5, 10
Synthetic route to Compounds I
Wherein, the substituents Het and R are defined as the above; het is selected from: thiazol-2, 4-yl, thiazol-4, 2-yl; r is selected from: phenyl, 2-chlorophenyl, 4-chlorophenyl, 2, 4-dichlorophenyl, 4-fluorophenyl, 4-methylphenyl, 4-trifluoromethylphenyl, 4-trifluoromethoxyphenyl; n is 2 to 4.
The synthetic method of the difluoropyrazole heterocyclic formamide derivative is the same as that in patent CN 110128419A
The invention provides application of the difluoropyrazole thiazole methanamide derivative I in preparation of a fungicide.
The invention provides application of the difluoropyrazole thiazole methanamide derivative I in preparation of an anti-tobacco mosaic virus agent.
The invention provides application of difluoropyrazole thiazole methanamide derivatives I in preparation of plant activators for inducing tobacco to resist tobacco mosaic virus.
The invention provides application of the difluoropyrazole thiazole methanamide derivative I in preventing and treating agricultural and forestry and horticultural plant insect pests.
Co-applying the difluoropyrazole thiazole carboxamide derivative I with an agrochemical; the agrochemical is selected from: one or more of insecticide, bactericide, plant virus resisting agent and acaricide.
The difluoropyrazole thiazole methanamide derivative I and any one or two of the insecticides are combined to form an insecticidal composition for preventing and controlling agricultural and forestry and horticultural plant insect pests;
the insecticide is selected from: methoprene, diazinon, acetamiprid, emamectin benzoate, milbemectin, abamectin, pleocidin, metaflumethrin, meperfluthrin, cyfluthrin, beta-cypermethrin, lambda-cyhalothrin, permethrin, allethrin, bifenthrin, permethrin, flumethrin, cyfluthrin, imidacloprid, nitenpyram, imidaclothianidin, thiacloprid, thiamethoxam, clothianidin, dinotefuran, cotinine, dinotefuran, diflubenzuron, chlorbenzuron, tefluazuron, flufenoxuron, lufenuron, chlorflufenoxuron, fluazuron, diflubenzuron, fluazuron, tezine, fluazuron, tezine, teflufenozide, tebufenozide, tezine, flufenozide, tebufenozide, tezine, tebufenozide, methoxyfenozide, chromafenozide, dichlorvos, quinalphos, pyridaphenthion, cicada powder, carbaryl, pirimicarb, metolcarb, isoprocarb, cartap, fenobucarb, tetrafenozide, fenitrothion, hexythiazox, carbaryl, fenisobromolate, hexythiazox, pyridate, clofentezine, spirodiclofen, spirotetramat, butirofenthiuron, buprofezin, monosultap, dimehypo, chlorantraniliprole, tetrachlorantranilide, flubendiamide, cyhalodiamide, butenafloxacin, tolfenpyrad, chlorfenapyr, pyraflufen, pyrazinone, etoxazole, tebufenpyrad, pyridaben, emamectin, and guadipyridamole;
the mass percentage of the difluoropyrazole thiazole methanamide derivative I in the insecticidal composition is 1-90%; preferably, the mass percentage of the difluoropyrazole thiazole methanamide derivative I to the pesticide is 1 percent to 99 percent to 1 percent;
the insecticide composition is processed into a dosage form selected from the group consisting of: seed treatment emulsions, aqueous emulsions, microemulsions, suspoemulsions, capsule suspensions, water soluble granules, fine granules, soluble concentrates, venoms, block baits, granular baits, tablet baits, concentrated baits, sustained release blocks, electrostatic sprays, oil-in-water emulsions, aerosol cans, aerosol candles, aerosol cartridges, aerosol sticks, aerosol tablets, aerosol pellets, gas generants, ointments, hot fogging formulations, cold fogging formulations, aerosols, solid/liquid mixtures, liquid/liquid mixtures, solid/solid mixtures, lacquers, microgranules, chasing powders, oil suspensions, oil dispersible powders, concentrated gels, pour-on formulations, seed coatings, paints, film-forming oils, ultra-low volume liquids, vapor release agents;
the plant insect pests protected by the insecticidal composition are selected from: spodoptera frugiperda, red spider, locusta tenella, locusta sprengeri, chinese rice locust, burley locust, mole cricket orientalis, thrips oryzae, thrips tabaci, thrips oryzae, thrips tritici, aleyrodids fumosoroseus, cicada melanogaster, big leafhopper, cotton leafhopper, lesser leafhopper, brown plant hopper, white back plant hopper, gray plant hopper, sugarcane planthopper, cotton aphid, binary aphid, wheat aphid, green pipe aphid, peach aphid, sorghum aphid, radish aphid, mealybug, lybug, lygus bugs, arrowhead bug, round green scale, white wax insect, red wax insect, armyworm, green ball nut, pear netting, banana netting, stinkbug, tiny laceleaf fly, green fly, rice bollworm, rice moth, black armyworm, black rice moth, black rice green peach, Pink bollworm, sweet potato wheat moth, diamond back moth, peach fruit borer, soybean pod borer, peach fruit borer, apple tip leaf roller moth, brown banded leaf roller moth, pardos leaf roller moth, striped rice borer, pod borer, corn borer, yellow rice borer, cabbage moth, rice leaf roller borer, striped rice borer, cotton leaf borer, peach borer, armyworm, prodenia litura, rice bollworm, cotton small bridgehead moth, beet armyworm, sesamia inferen, cotton bollworm, Dinodon diamond-back moth, agrotis, yellow cutworm, robber venom moth, gypsy moth, sweet potato hawkmoth, bean hawkmoth, straight grain rice skipper, cryptophyte butterfly, caeruleuca, caeruleuciscus nigra, yellow mealyratus caeruleucade, yellow meadowrue, yellow rice beetle, yellow tiger, red ramie yellow vanne, yellow rice borer, yellow rice, Tribolium castaneum, verdigris, black tortoise, branchia palustris, longicorn beetle, pink neck longicorn beetle, ape leaf worm, yellow melon, flea beetle, mung bean weevil, pea weevil, broad bean weevil, corn weevil, rice weevil, wheat leaf bee, pear fruit bee, yellow stripe wasp, armyworm white star ichneumonid, sandfly bractenoconid, cotton bollworm tooth-lipped ichneumonid, borer black spot wart, mosquito, fly, horsefly, red mud fly, yellow leaf sucking serous, rice gall mosquito fly, citrus fruit fly, melon fruit fly, wheat leaf gray fly, American fly, black stalk black fly, wheat stem fly, seed fly, onion fly, radish skirt, eupatorium, corn borer, and armyworm;
the plants protected by the insecticidal composition are as follows: rice, wheat, barley, oats, corn, sorghum, sweet potato, cassava, soybean, sweet broad bean, pea, mung bean, small bean, cotton, silkworm, peanut, rape, sesame, sunflower, sugar beet, sugarcane, coffee, cocoa, ginseng, fritillaria, rubber, coconut, oil palm, sisal, tobacco, tomato, chili, radish, cucumber, cabbage, celery, tuber mustard, sugar beet, rape, shallot, garlic, watermelon, melon, cantaloupe, papaya, apple, citrus, peach, tea, wild vegetables, bamboo shoots, hops, pepper, banana, papaya, orchid, bonsai.
The difluoropyrazole thiazole methanamide derivative I and any one or two of the bactericides are combined to form a bactericidal composition for preventing and treating diseases of agricultural, forestry and horticultural plants;
the bactericide is selected from: benzothiadiazole, tiadinil, thianamide, methicillin, 4-methyl-1, 2, 3-thiadiazole-5-carboxylic acid, 4-methyl-1, 2, 3-thiadiazole-5-sodium formate, 4-methyl-1, 2, 3-thiadiazole-5-ethyl formate, DL-beta-aminobutyric acid, isotianil, 3, 4-dichloroisothiazole-5-carboxylic acid, 3, 4-dichloroisothiazole-5-sodium formate, 3, 4-dichloroisothiazole-5-ethyl formate, ribavirin, antofine, ningnanmycin or salicylic acid, cyanamide, thiram, ziram, mancozeb, fosetyl, thiophanate-methyl, chlorothalonil, chlormadinone, procymidone, fenpropidium rust, Thiophanate methyl, thiophanate, metalaxyl-M, flumorph, dimethomorph, metalaxyl-M, benalaxyl-M, diclocyanamide, sulfentram, sulfsulfamide, thifluzamide, folpet, cyprodinil, cyhalodiamide, silthiopham, carboxin, oxim-methyl, mefuram, fenazamide, flutolanil, furametpyr, thifluzamide, boscalid, penthiopyrad, isopyrazamide, bixafen, fluopyram, fluxastrobin, fluxapyroxad, flufenapyr, benconazole, iprovalicarb, flutriafolan, flufenpyrazamide, flufenacetmid, fluoxastrobin, fenhexamid, iprodione, trifloxystrobin, kresoximtrobin, trifloxystrobin, fenstrobin, fenstrobilurin, fenpyraclostrobin, fluoxastrobin, fluoxastrobilurin, fluoxastrobil, Enestroburin, dimethomorph, difenoconazole, bromhexine, epoxiconazole, bromuconazole, cyproconazole, difenoconazole, diniconazole, difenoconazole, epoxiconazole, fenbuconazole, fluquinconazole, flusilazole, flutriafol, hexaconazole, imibenconazole, ipconazole, metconazole, myclobutanil, penconazole, propiconazole, prothioconazole, simeconazole, tebuconazole, tetraconazole, triadimenol, triticonazole, bitertanol, thiabendazole, imazalil, prochloraz, triflumizole, cyazofamid, fenamidone, imidazole, pefurazoate, famoxadone, pyridinozole, prodiamine, ethaboxam, hymexazol, penoxsulam, fenthion, fenpropimorph, tridemorph, fenpyroxanil, fluazinam, fenpropiconazole, fenpyrazamide, fluazinam, cyprodinil, flufenamidone, fenpyrad, fenpyro, Mepanipyrim, pyrimethanil, fenarimol, fluoropyrimidinol, mefenamate, dithianon, ethoxyquin, hydroxyquinoline, propoxymine, phenoxyquinoline, diethofencarb, iprovalicarb, benthiavalicarb, propamocarb, sulbencarb, edifenphos, iprobenfos, pyrazofos, tolclofos-methyl, blasticidin, kasugamycin, polyoxin, validamycin, streptomycin, metalaxyl, furalaxyl, benomyl, thiophanate-methyl, triadimefon, bupirimate, dimethirimol, ethirimol, captan, folpet, vinclozolin, fluocinolone, dimethachlon, chlorothalonil, isoprothiolane, pefurazone, bismerzole, quintozene, propineb, fosetyl, sulfur, polidocusate, cuprous oxide, cupric chloride, cupric oxide, cupric hydroxide, Metrafenone, pencycuron, pyridaben, tetrachlorophthalide, pyroquilon, spiroxamine, tricyclazole, azinam, dodine, diguanidinium salt, diguanidinium, niclosamide, bentiamine, tolfenpyrad, indole ester, sodium disulfate, quinconazole, probenazole, bronopol, methyl iodide, metam, dichloline ester, dazomet, dichloroisopropyl ether, fosthiazate, fosfenthion, fenamiphos, thiothifenthion, methiocarb, sulfuryl fluoride, dichloropropylene, dichloroisonicotinic acid, allylisothiazole;
the difluoropyrazole thiazole methanamide derivative I accounts for 1-90% of the total mass of the bactericidal composition; the mass percentage of the difluoropyrazole thiazole methanamide derivative I to the bactericide is 1 percent to 99 percent to 1 percent;
the bactericidal composition is processed into a dosage form selected from the group consisting of: seed treatment emulsions, aqueous emulsions, microemulsions, suspoemulsions, capsule suspensions, water soluble granules, fine granules, soluble concentrates, venoms, block baits, granular baits, tablet baits, concentrated baits, sustained release blocks, electrostatic sprays, oil-in-water emulsions, aerosol cans, aerosol candles, aerosol cartridges, aerosol sticks, aerosol tablets, aerosol pellets, gas generants, ointments, hot fogging formulations, cold fogging formulations, aerosols, solid/liquid mixtures, liquid/liquid mixtures, solid/solid mixtures, lacquers, microgranules, chasing powders, oil suspensions, oil dispersible powders, concentrated gels, pour-on formulations, seed coatings, paints, film-forming oils, ultra-low volume liquids, vapor release agents;
the plant diseases protected by the bactericidal composition are selected from the following group: rice seedling blight, tomato root rot, potato late blight, tobacco black shank, millet powdery mildew, grape downy mildew, lettuce downy mildew, cucumber anthracnose;
the plants suitable for the bactericidal composition are selected from the group consisting of: rice, wheat, barley, oats, corn, sorghum, sweet potato, cassava, soybean, sweet broad bean, pea, mung bean, small bean, cotton, silkworm, peanut, rape, sesame, sunflower, sugar beet, sugarcane, coffee, cocoa, ginseng, fritillaria, rubber, coconut, oil palm, sisal, tobacco, tomato, chili, radish, cucumber, cabbage, celery, tuber mustard, sugar beet, rape, shallot, garlic, watermelon, melon, cantaloupe, papaya, apple, citrus and peach, tea, wild vegetables, bamboo shoots, hops, pepper, banana, papaya, orchid, bonsai.
The difluoropyrazole thiazole methanamide derivative I and any one or two of the antiviral medicaments are combined to form an antiviral composition for preventing and treating virus diseases of agricultural, forestry and horticultural plants;
the antiviral agent is selected from: benzothiadiazole, tiadinil, isotianil, 4-methyl-1, 2, 3-thiadiazole-5-carboxylic acid, 4-methyl-1, 2, 3-thiadiazole-5-sodium formate, 4-methyl-1, 2, 3-thiadiazole-5-ethyl formate, 3, 4-dichloroisothiazole-5-carboxylic acid, 3, 4-dichloroisothiazole-5-sodium formate, 3, 4-dichloroisothiazole-5-ethyl formate, DL-beta-aminobutyric acid, 2, 6-dichloroisonicotinic acid, N-cyanomethyl-2-chloroisonicotinamide, probenazole, virazole, antofine, ningnanmycin, thiamide, methiothiamide or salicylic acid, pyriminomycin, Dichloroisonicotinic acid, probenazole, validamycin, moroxydine hydrochloride;
the total mass percentage of the difluoropyrazole thiazole methanamide derivative I in the antiviral composition is 1-90%; preferably, the ratio of the difluoropyrazole thiazole carboxamide derivative I to the anti-plant virus agent is 1 percent to 99 percent to 1 percent in percentage by mass;
the antiviral composition is processed into a dosage form selected from: seed treatment emulsions, aqueous emulsions, microemulsions, suspoemulsions, capsule suspensions, water soluble granules, fine granules, soluble concentrates, venoms, block baits, granular baits, tablet baits, concentrated baits, sustained release blocks, electrostatic sprays, oil-in-water emulsions, aerosol cans, aerosol candles, aerosol cartridges, aerosol sticks, aerosol tablets, aerosol pellets, gas generants, ointments, hot fogging formulations, cold fogging formulations, aerosols, solid/liquid mixtures, liquid/liquid mixtures, solid/solid mixtures, lacquers, microgranules, chasing powders, oil suspensions, oil dispersible powders, concentrated gels, pour-on formulations, seed coatings, paints, film-forming oils, ultra-low volume liquids, vapor release agents;
the antiviral composition can be used for preventing and treating viral diseases selected from: rice dwarf, yellow dwarf, stripe disease, tomato fern leaf virus, pepper mosaic virus, tobacco vein necrosis virus, maize dwarf mosaic, cauliflower mosaic, citrus virus, cymbidium mosaic, cymbidium ringspot virus;
the plant protected by the antiviral composition is selected from the following plants: rice, wheat, barley, oats, corn, sorghum, sweet potato, cassava, soybean, sweet broad bean, pea, mung bean, small bean, cotton, silkworm, peanut, rape, sesame, sunflower, sugar beet, sugarcane, coffee, cocoa, ginseng, fritillaria, rubber, coconut, oil palm, sisal, tobacco, tomato, chili, radish, cucumber, cabbage, celery, tuber mustard, sugar beet, rape, shallot, garlic, watermelon, melon, cantaloupe, papaya, apple, citrus and peach, tea, wild vegetables, bamboo shoots, hops, pepper, banana, papaya, orchid, bonsai.
The difluoropyrazole thiazole methanamide derivative I and any one or two of the acaricides are combined to form an acaricide composition for preventing and controlling mite damage of agricultural and forestry and horticultural plants;
the acaricide is selected from: dichlorvos, heptenophos, metofos, monocrotophos, phosphorus dibromide, pyrimidophos, chloromethylthion, ethion, chlorfenvinphos, vofenthion, pirimiphos, phoxim, isocarbophos, amicarbazone, chlormephos, fluthrin, bifenthrin, cyhalothrin, lambda-cyhalothrin, fenpropathrin, flumethrin, fluvalinate, bifenthrin, bifenazate, fenobucarb, butoxycarb, carbofuran, monocarb, benomyl, cloxacarb, butathiocarb, lufenuron, benzyl benzoate, bromopropylate, cyflumetofen, dimethrin, flufenpyr, fluazuron, bleomycin, chlortetracycline, abamectin, avermectin, lium, lividin, doramectin, epothidin, ivermectin, simethiofen, dimethofos, dimethrin, dimethoxim, fosetyl, chlorfenapyr, isofos, chlorfenapyr, dimethoxim, fluazurin, Nicotine, matrine, azadirachtin, rotenone, tebufenpyrad, pyridaben, fenpyroximate, clofentezine, propargite, hexythiazox, spirodiclofen, fluacrypyrim, propargite and pyridaben;
the difluoropyrazole thiazole methanamide derivative I accounts for 1-90% of the acaricidal composition in total mass percentage; the ratio of the difluoropyrazole thiazole methanamide derivative I to the acaricide is 1 to 99 to 1 percent in percentage by mass;
the acaricidal composition is processed into a dosage form selected from the following: seed treatment emulsions, aqueous emulsions, microemulsions, suspoemulsions, capsule suspensions, water soluble granules, fine granules, soluble concentrates, venoms, block baits, granular baits, tablet baits, concentrated baits, sustained release blocks, electrostatic sprays, oil-in-water emulsions, aerosol cans, aerosol candles, aerosol cartridges, aerosol sticks, aerosol tablets, aerosol pellets, gas generants, ointments, hot fogging formulations, cold fogging formulations, aerosols, solid/liquid mixtures, liquid/liquid mixtures, solid/solid mixtures, lacquers, microgranules, chasing powders, oil suspensions, oil dispersible powders, concentrated gels, pour-on formulations, seed coatings, paints, film-forming oils, ultra-low volume liquids, vapor release agents;
the mite damage controlled by the mite-killing composition is selected from the following groups: the mite is selected from spider mite family, furaciidae, gall mite family, Tetranychus genus, and pest mites of gall mite family, which are world agricultural pest mites, forestry pest mites, horticultural pest mites, and health pest mites;
the plant for protecting the acaricidal composition is selected from the following plants: rice, wheat, barley, oats, corn, sorghum, sweet potato, cassava, soybean, sweet broad bean, pea, mung bean, small bean, cotton, silkworm, peanut, rape, sesame, sunflower, sugar beet, sugarcane, coffee, cocoa, ginseng, fritillaria, rubber, coconut, oil palm, sisal, tobacco, tomato, chili, radish, cucumber, cabbage, celery, tuber mustard, sugar beet, rape, shallot, garlic, watermelon, melon, cantaloupe, papaya, apple, citrus and peach, tea, wild vegetables, bamboo shoots, hops, pepper, banana, papaya, orchid, bonsai.
The biological activity of the difluoropyrazole thiazole methanamide derivative I is determined as follows:
and N, bactericidal activity determination of the difluoropyrazole thiazole carboxamide derivative I:
the bactericidal or bacteriostatic activity of the difluoropyrazole thiazole formamide I adopts a thallus growth rate measuring method, and the specific steps are as follows: dissolving 1.8 mg of sample in 2 drops of N, N-dimethylformamide, diluting with a water solution containing a certain amount of Tween 20 emulsifier to 500 micrograms/ml of medicament, sucking 1 ml of the medicament to be tested in a culture dish under an aseptic condition, adding 9 ml of PDA culture medium, shaking uniformly to prepare a medicament-containing flat plate with the concentration of 50 micrograms/ml, taking the flat plate added with 1 ml of sterile water as a blank control, cutting a bacterial disc by a puncher with the diameter of 4 mm along the outer edge of hypha, moving the bacterial disc to the medicament-containing flat plate, placing the bacterial disc in an equilateral triangle, repeating the treatment for 3 times, placing the culture dish in a constant temperature incubator with the temperature of 24 +/-1 ℃ for culture, investigating the expansion diameter of each treated bacterial disc after the diameter of the control bacterial colony is expanded to 2-3 cm, calculating the relative bacteriostasis rate by comparing with the blank control, wherein the strain is the species of most typical plant pathogenic bacteria actually occurring in the agricultural production of China, the code numbers and names are as follows: AS: tomato early blight, its latin name is: alternaria solani, BC: the cucumber botrytis cinerea with the latin name as follows: botrytis cinerea, CA: peanut brown spot pathogen, its latin name is: cercospora arachidicola, GZ: wheat scab, its latin name is: gibberella zeae, PI: the late blight of potato, its latin name is: phytophthora infestans (Mont.) de Bary, PP: apple ring rot, its latin name is: physiosporia piricola, PS: rhizoctonia solani, the Latin name of which is: pellicularia sasakii, RC: rhizoctonia cerealis, with the latin name: rhizoctonia cerealis, SS: sclerotinia sclerotiorum, its latin name is: sclerotina sclerotiorum.
The invention has the beneficial effects that: the difluoropyrazole thiazole carboxamide derivative I is subjected to lead optimization, and the difluoropyrazole thiazole carboxamide derivative is subjected to screening of antibacterial activity.
The synthesis, biological activity and application of difluoropyrazole thiazole carboxamide derivative I are more specifically illustrated by specific preparation and biological activity determination examples, which are only used for specifically illustrating the invention and not limiting the invention, in particular, the biological activity is only illustrated and not limiting the patent, and the specific embodiments are as follows:
example 1: preparation of Compound HZS-1-65:
a50 ml single neck round bottom flask was charged with 0.58 mmol of 1, 1.16 mmol of N, N-diisopropylethylamine dissolved in dichloromethane and stirred at room temperature. Adding 0.64 mmol of benzotriazole-1-yl-oxytripyrrolidinophosphonium hexafluorophosphate (PyBop) under the ice-bath condition, stirring for 15 minutes, adding 0.58 mmol of 2, stirring at room temperature overnight, washing with 10 ml of water, separating the water outlet layer, extracting twice with dichloromethane (5 ml. times.2), combining the organic layers, washing once with 10 ml of saturated sodium chloride solution, separating the water outlet layer, extracting twice with dichloromethane (5 ml. times.2), combining the organic layers, and drying with anhydrous sodium sulfate; vacuum filtering, concentrating the filtrate to remove solvent, and purifying by column chromatography with petroleum ether/ethyl acetate (4: 1, volume/volume) eluent to obtain corresponding product I with yield: 87 percent; the nuclear magnetic data are as follows:1H NMR(400MHz，CDCl3) δ 8.01(s, 1H), 7.84(s, 1H), 7.33(s, 1H), 7.16(s, 4H), 6.97(t, J ═ 53.9Hz, 1H), 3.97(s, 3H), 3.70(q, J ═ 6.7Hz, 2H), 2.89(t, J ═ 6.9Hz, 2H), 2.34(s, 3H). The preparation amount of the compound and the volume of the reaction vessel are enlarged or reduced according to the corresponding proportion; the physicochemical and structural parameters of the compounds are shown in Table 1.
Example 2: the antibacterial activity determination result of the difluoropyrazole thiazole methanamide derivative I comprises the following steps:
the codes and names of the common plant pathogenic fungi tested by the invention are as follows: AS: tomato early blight, its latin name is: alternaria solani, BC: the cucumber botrytis cinerea with the latin name as follows: botrytis cinerea, CA: peanut brown spot pathogen, its latin name is: cercospora arachidicola, GZ: wheat scab, its latin name is: gibberella zeae, PI: the late blight of potato, its latin name is: phytophthora infestans (Mont.) de Bary, PP: apple ring rot, its latin name is: physiosporia piricola, PS: rhizoctonia solani, the Latin name of which is: pellicularia sasakii, RC: rhizoctonia cerealis, named latin: rhizoctonia cerealis, SS: sclerotinia sclerotiorum, its latin name is: the strains have good representativeness and can represent the species of most pathogenic bacteria in the field in agricultural production.
The results of the cell growth rate method are shown in Table 2, and Table 2 shows that all the compounds synthesized by the invention have bactericidal activity of different degrees at 50 micrograms/ml. The chemical structure reported in patent CN 110128419a is closest to the chemical structure of the present invention. The bactericidal activity of part of the compounds of the invention on specific strains is better than that of the compounds with the best bactericidal activity in the compounds reported in patent CN 110128419A, that is, the bactericidal activity of the target compound is unexpectedly and greatly improved due to the introduction of specific groups. For botrytis cinerea, the inhibition rate of the compounds HZS-1-89, HZS-1-63, HZS-1-82 and HZS-1-65 of the invention reaches more than 50%, wherein the bactericidal activity of the compounds HZS-1-89 reaches 86%, which is more than 20% higher than that of the control thifluzamide, and is superior to the compound YB02-154 (78%) with the best activity reported in patent CN 110128419A; the activity on the wheat scabies shows that the inhibition rates of the compounds HZS-1-62, HZS-1-63, HZS-1-82, HZS-1-65, HZS-1-81, HZS-1-67, HZS-1-83, HZS-1-84, HZS-1-69, HZS-1-86, HZS-1-71 and HZS-1-72 are all higher than 50 percent and are better than those of the control drugs fluxapyroxad and thifluzamide, particularly the bactericidal activity of the compounds HZS-1-65 is highest and reaches 71 percent; for ring rot apple germs, the inhibition rate of the compound HZS-1-90 is 45 percent, which is equivalent to that of the control drugs fluxapyroxad and thifluzamide; for sclerotinia sclerotiorum, the bactericidal activity of the compounds HZS-1-84, HZS-1-90, HZS-1-82, HZS-1-81, HZS-1-70, HZS-1-86, HZS-1-85, HZS-1-69 and HZS-1-71 is more than 80 percent, and is equivalent to that of the control drugs fluxapyroxad and thifluzamide, wherein the inhibition rate of the compounds HZS-1-85 is more than 90 percent, is better than that of the control drugs fluxad and thifluzamide, and is equivalent to that of the compound YB02-117(97 percent) with the best activity reported in patent CN 110128419A; for rhizoctonia cerealis, the bactericidal activity of the compounds HZS-1-63, HZS-1-82, HZS-1-65, HZS-1-81, HZS-1-66, HZS-1-86, HZS-1-90, HZS-1-67, HZS-1-83, HZS-1-84, HZS-1-85, HZS-1-86, HZS-1-71 is more than 70%, which is more than 10% higher than that of the control drugs fluxapyroxad and thifluzamide, especially the bactericidal activity of the compounds HZS-1-84 is the highest and reaches 91%, which is nearly 50% higher than that of the control drug fluxapyroxad, which is better than the best-active YB02-166 (90%) reported in the compound patent CN 110128419 a; the activity on rice sheath blight bacteria shows that the bactericidal activity of the compounds HZS-1-63, HZS-1-65, HZS-1-90 and HZS-1-84 is over 50 percent and is over 30 percent higher than that of the control drugs fluxapyroxad and thifluzamide; for potato late blight bacteria, the bactericidal activity of the compounds HZS-1-63, HZS-1-65, HZS-1-81 and HZS-1-84 is more than 40 percent, and the bactericidal activity is superior to that of fluxapyroxad and thifluzamide serving as control drugs.
Example 3: the application of the difluoropyrazole thiazole methanamide derivative I in the preparation of the pesticide composition comprises the following steps:
the difluoropyrazole thiazole methanamide derivative I is used for preparing a pesticide composition, the composition contains the difluoropyrazole thiazole methanamide derivative I and an intermediate thereof as active ingredients, the content of the active ingredients is 0.1 to 99.9 percent by weight, 99.9 to 0.1 percent by weight of solid or liquid auxiliary agents and optional 0 to 50 percent by weight of surfactant.
Example 4: the application of the difluoropyrazole thiazole methanamide derivative I in the preparation of the pesticide compound composition comprises the following steps:
the difluoropyrazole thiazole methanamide derivative I and the intermediate thereof can be used for preparing other commercial pesticides, namely insecticide, acaricide, bactericide, antiviral agent or plant activator, to prepare the pesticide compound composition, the compound composition comprises the difluoropyrazole thiazole methanamide derivative I and the intermediate thereof and other commercial pesticides, namely an insecticide, an acaricide, a bactericide, an antiviral agent or a plant activator as an active ingredient, the difluoropyrazole thiazole carboxamide derivative I and the intermediate thereof of the invention and other commercial pesticides, the proportion of the insecticide, acaricide, bactericide, antiviral agent or plant activator is 1 percent to 99 percent to 1 percent by mass, the content of the active ingredient is 0.1 percent to 99.9 percent by weight, 99.9 percent to 0.1 percent by weight of solid or liquid auxiliary agent and optional 0 percent to 50 percent by weight of surfactant.
Example 5: the application of the difluoropyrazole thiazole methanamide derivative I and the pesticide composition in preventing and treating agricultural, forestry and horticultural plant insect pests is as follows:
the difluoropyrazole thiazole methanamide derivative I and any one or two of commercial insecticides are combined to form an insecticidal composition for preventing and treating agricultural and forestry and horticultural plant insect pests, wherein the commercial insecticide is selected from the following components: methoprene, diazinon, acetamiprid, emamectin benzoate, milbemectin, abamectin, pleocidin, metaflumethrin, meperfluthrin, cyfluthrin, beta-cypermethrin, lambda-cyhalothrin, permethrin, allethrin, bifenthrin, permethrin, flumethrin, cyfluthrin, imidacloprid, nitenpyram, imidaclothianidin, thiacloprid, thiamethoxam, clothianidin, dinotefuran, cotinine, dinotefuran, diflubenzuron, chlorbenzuron, tefluazuron, flufenoxuron, lufenuron, chlorflufenoxuron, fluazuron, diflubenzuron, fluazuron, tezine, fluazuron, tezine, teflufenozide, tebufenozide, tezine, flufenozide, tebufenozide, tezine, tebufenozide, methoxyfenozide, chromafenozide, dichlorvos, quinalphos, pyridaphenthion, cicada powder, carbaryl, pirimicarb, metolcarb, isoprocarb, cartap, fenobucarb, tetrafenozide, fenitrothion, hexythiazox, carbaryl, fenisobromolate, hexythiazox, pyridate, clofentezine, spirodiclofen, spirotetramat, butirofenthiuron, buprofezin, monosultap, dimehypo, chlorantraniliprole, tetrachlorantranilide, flubendiamide, cyhalodiamide, butenafloxacin, tolfenpyrad, chlorfenapyr, pyraflufen, pyrazinone, etoxazole, tebufenpyrad, pyridaben, emamectin, and guadipyridamole; the mass percentage of the difluoropyrazole thiazole methanamide derivative I in the insecticidal composition is 1-90%, and the mass percentage of the difluoropyrazole thiazole methanamide derivative I and the commercial insecticide is 1% to 99% to 1%; the insecticide composition is processed into a dosage form selected from the group consisting of: seed treatment emulsions, aqueous emulsions, microemulsions, suspoemulsions, capsule suspensions, water soluble granules, fine granules, soluble concentrates, venoms, block baits, granular baits, tablet baits, concentrated baits, sustained release blocks, electrostatic sprays, oil-in-water emulsions, aerosol cans, aerosol candles, aerosol cartridges, aerosol sticks, aerosol tablets, aerosol pellets, gas generants, ointments, hot fogging formulations, cold fogging formulations, aerosols, solid/liquid mixtures, liquid/liquid mixtures, solid/solid mixtures, lacquers, microgranules, chasing powders, oil suspensions, oil dispersible powders, concentrated gels, pour-on formulations, seed coatings, paints, film-forming oils, ultra-low volume liquids, vapor release agents; the plant insect pests protected by the insecticidal composition are selected from: meadow spodoptera, red spider, east Asian migratory locust, spruce-bug, Chinese rice locust, japanese yellow-back locust, single-prick mole cricket, oriental mole cricket, rice thrips, thrips tabaci, green house thrips, rice straw thistle, wheat simple pipe thrips, green house whitefly, bemisia tabaci, black tail hopper, big leaf hopper, cotton leafhopper, lesser leafhopper, brown plant hopper, white back plant hopper, gray plant hopper, sugarcane flat leaf planthopper, cotton aphid, binary wheat aphid, wheat straw aphid, peach aphid, sorghum aphid, radish aphid, mealybug, lybug, stinkbug, arrowhead bug, round scale, white insect, red wax insect, red worm, mealybug, pear net, banana net bug, tiny flower bug, laceleaf fly, green fly, rice moth, black armyworm, black fly, black rice moth, black armyworm, black rice moth, black rice plant, pink bollworm, sweet potato wheat moth, diamond back moth, peach fruit borer, soybean pod borer, peach fruit borer, apple tip leaf roller moth, brown banded leaf roller moth, pardos leaf roller moth, striped rice borer, pod borer, corn borer, yellow rice borer, cabbage moth, rice leaf roller borer, striped rice borer, cotton leaf borer, peach borer, armyworm, prodenia litura, rice bollworm, cotton small bridgehead moth, beet armyworm, sesamia inferen, cotton bollworm, Dinodon diamond-back moth, agrotis, yellow cutworm, robber venom moth, gypsy moth, sweet potato hawkmoth, bean hawkmoth, straight grain rice skipper, cryptophyte butterfly, caeruleuca, caeruleuciscus nigra, yellow mealyratus caeruleucade, yellow meadowrue, yellow rice beetle, yellow tiger, red ramie yellow vanne, yellow rice borer, yellow rice, Tribolium castaneum, verdigris, black tortoise, branchia palustris, longicorn beetle, pink neck longicorn beetle, ape leaf worm, yellow melon, flea beetle, mung bean weevil, pea weevil, broad bean weevil, corn weevil, rice weevil, wheat leaf bee, pear fruit bee, yellow stripe wasp, armyworm white star ichneumonid, sandfly bractenoconid, cotton bollworm tooth-lipped ichneumonid, borer black spot wart, mosquito, fly, horsefly, red mud fly, yellow leaf sucking serous, rice gall mosquito fly, citrus fruit fly, melon fruit fly, wheat leaf gray fly, American fly, black stalk black fly, wheat stem fly, seed fly, onion fly, radish skirt, eupatorium, corn borer, and armyworm; the plants protected by the insecticidal composition are selected from the group consisting of: rice, wheat, barley, oats, corn, sorghum, sweet potato, cassava, soybean, sweet broad bean, pea, mung bean, small bean, cotton, silkworm, peanut, rape, sesame, sunflower, sugar beet, sugarcane, coffee, cocoa, ginseng, fritillaria, rubber, coconut, oil palm, sisal, tobacco, tomato, chili, radish, cucumber, cabbage, celery, tuber mustard, sugar beet, rape, shallot, garlic, watermelon, melon, cantaloupe, papaya, apple, citrus and peach, tea, wild vegetables, bamboo shoots, hops, pepper, banana, papaya, orchid, bonsai.
Example 6: the application of the difluoropyrazole thiazole methanamide derivative I and the bactericide composition in preventing and treating agricultural, forestry and horticultural plant diseases is as follows:
the difluoropyrazole thiazole methanamide derivative I and any one or two of commercial bactericides form a bactericidal composition for preventing and treating agricultural and forestry and horticultural plant diseases, wherein the commercial bactericides are selected from: benzothiadiazole, tiadinil, thianamide, methicillin, 4-methyl-1, 2, 3-thiadiazole-5-carboxylic acid, 4-methyl-1, 2, 3-thiadiazole-5-sodium formate, 4-methyl-1, 2, 3-thiadiazole-5-ethyl formate, DL-beta-aminobutyric acid, isotianil, 3, 4-dichloroisothiazole-5-carboxylic acid, 3, 4-dichloroisothiazole-5-sodium formate, 3, 4-dichloroisothiazole-5-ethyl formate, ribavirin, antofine, ningnanmycin or salicylic acid, cyanamide, thiram, ziram, mancozeb, fosetyl, thiophanate-methyl, chlorothalonil, chlormadinone, procymidone, fenpropidium rust, Thiophanate methyl, thiophanate, metalaxyl-M, flumorph, dimethomorph, metalaxyl-M, benalaxyl-M, diclocyanamide, sulfentram, sulfsulfamide, thifluzamide, folpet, cyprodinil, cyhalodiamide, silthiopham, carboxin, oxim-methyl, mefuram, fenazamide, flutolanil, furametpyr, thifluzamide, boscalid, penthiopyrad, isopyrazamide, bixafen, fluopyram, fluxastrobin, fluxapyroxad, flufenapyr, benconazole, iprovalicarb, flutriafolan, flufenpyrazamide, flufenacetmid, fluoxastrobin, fenhexamid, iprodione, trifloxystrobin, kresoximtrobin, trifloxystrobin, fenstrobin, fenstrobilurin, fenpyraclostrobin, fluoxastrobin, fluoxastrobilurin, fluoxastrobil, Enestroburin, dimethomorph, difenoconazole, bromhexine, epoxiconazole, bromuconazole, cyproconazole, difenoconazole, diniconazole, difenoconazole, epoxiconazole, fenbuconazole, fluquinconazole, flusilazole, flutriafol, hexaconazole, imibenconazole, ipconazole, metconazole, myclobutanil, penconazole, propiconazole, prothioconazole, simeconazole, tebuconazole, tetraconazole, triadimenol, triticonazole, bitertanol, thiabendazole, imazalil, prochloraz, triflumizole, cyazofamid, fenamidone, imidazole, pefurazoate, famoxadone, pyridinozole, prodiamine, ethaboxam, hymexazol, penoxsulam, fenthion, fenpropimorph, tridemorph, fenpyroxanil, fluazinam, fenpropiconazole, fenpyrazamide, fluazinam, cyprodinil, flufenamidone, fenpyrad, fenpyro, Mepanipyrim, pyrimethanil, fenarimol, fluoropyrimidinol, mefenamate, dithianon, ethoxyquin, hydroxyquinoline, propoxymine, phenoxyquinoline, diethofencarb, iprovalicarb, benthiavalicarb, propamocarb, sulbencarb, edifenphos, iprobenfos, pyrazofos, tolclofos-methyl, blasticidin, kasugamycin, polyoxin, validamycin, streptomycin, metalaxyl, furalaxyl, benomyl, thiophanate-methyl, triadimefon, bupirimate, dimethirimol, ethirimol, captan, folpet, vinclozolin, fluocinolone, dimethachlon, chlorothalonil, isoprothiolane, pefurazone, bismerzole, quintozene, propineb, fosetyl, sulfur, polidocusate, cuprous oxide, cupric chloride, cupric oxide, cupric hydroxide, Metrafenone, pencycuron, pyridaben, tetrachlorophthalide, pyroquilon, spiroxamine, tricyclazole, azinam, dodine, diguanidinium salt, diguanidinium, niclosamide, bentiamine, tolfenpyrad, indole ester, sodium disulfate, quinconazole, probenazole, bronopol, methyl iodide, metam, dichloline ester, dazomet, dichloroisopropyl ether, fosthiazate, fosfenthion, fenamiphos, thiothifenthion, methiocarb, sulfuryl fluoride, dichloropropylene, dichloroisonicotinic acid, allylisothiazole; the total mass percentage of the difluoropyrazole thiazole methanamide derivative I in the bactericidal composition is 1% -90%, and the mass percentage of the difluoropyrazole thiazole methanamide derivative I and the commercial bactericide is 1% to 99% to 1%; the bactericidal composition is processed into a dosage form selected from the group consisting of: seed treatment emulsions, aqueous emulsions, microemulsions, suspoemulsions, capsule suspensions, water soluble granules, fine granules, soluble concentrates, venoms, block baits, granular baits, tablet baits, concentrated baits, sustained release blocks, electrostatic sprays, oil-in-water emulsions, aerosol cans, aerosol candles, aerosol cartridges, aerosol sticks, aerosol tablets, aerosol pellets, gas generants, ointments, hot fogging formulations, cold fogging formulations, aerosols, solid/liquid mixtures, liquid/liquid mixtures, solid/solid mixtures, lacquers, microgranules, chasing powders, oil suspensions, oil dispersible powders, concentrated gels, pour-on formulations, seed coatings, paints, film-forming oils, ultra-low volume liquids, vapor release agents; the plant diseases protected by the bactericidal composition are selected from the following group: rice seedling blight, tomato root rot, potato late blight, tobacco black shank, millet powdery mildew, grape downy mildew, lettuce downy mildew, cucumber anthracnose; the plants suitable for the bactericidal composition are selected from the group consisting of: rice, wheat, barley, oats, corn, sorghum, sweet potato, cassava, soybean, sweet broad bean, pea, mung bean, small bean, cotton, silkworm, peanut, rape, sesame, sunflower, sugar beet, sugarcane, coffee, cocoa, ginseng, fritillaria, rubber, coconut, oil palm, sisal, tobacco, tomato, chili, radish, cucumber, cabbage, celery, tuber mustard, sugar beet, rape, shallot, garlic, watermelon, melon, cantaloupe, papaya, apple, citrus and peach, tea, wild vegetables, bamboo shoots, hops, pepper, banana, papaya, orchid, bonsai.
Example 7: the application of the difluoropyrazole thiazole carboxamide derivative I and the plant virus resisting agent in preventing and treating virus diseases of agricultural, forestry and horticultural plants is as follows:
the difluoropyrazole thiazole carboxamide derivative I and any one or two of commercial antiviral medicaments form an antiviral composition for preventing and treating virus diseases of agricultural, forestry and horticultural plants, wherein the commercial antiviral medicaments are selected from: benzothiadiazole, tiadinil, isotianil, 4-methyl-1, 2, 3-thiadiazole-5-carboxylic acid, 4-methyl-1, 2, 3-thiadiazole-5-sodium formate, 4-methyl-1, 2, 3-thiadiazole-5-ethyl formate, 3, 4-dichloroisothiazole-5-carboxylic acid, 3, 4-dichloroisothiazole-5-sodium formate, 3, 4-dichloroisothiazole-5-ethyl formate, DL-beta-aminobutyric acid, ribavirin, antofine, ningnanmycin, thiaamide, mehtothiazolamide or salicylic acid, pyriminomycin, dichloroisonicotinic acid, probenazole, validamycin hydrochloride; the total mass percentage content of the difluoropyrazole thiazole methanamide derivative I in the antiviral composition is 1-90%, and the mass percentage of the difluoropyrazole thiazole methanamide derivative I and the commercial anti-plant virus agent is 1-99-1%; the antiviral composition is processed into a dosage form selected from: seed treatment emulsions, aqueous emulsions, microemulsions, suspoemulsions, capsule suspensions, water soluble granules, fine granules, soluble concentrates, venoms, block baits, granular baits, tablet baits, concentrated baits, sustained release blocks, electrostatic sprays, oil-in-water emulsions, aerosol cans, aerosol candles, aerosol cartridges, aerosol sticks, aerosol tablets, aerosol pellets, gas generants, ointments, hot fogging formulations, cold fogging formulations, aerosols, solid/liquid mixtures, liquid/liquid mixtures, solid/solid mixtures, lacquers, microgranules, chasing powders, oil suspensions, oil dispersible powders, concentrated gels, pour-on formulations, seed coatings, paints, film-forming oils, ultra-low volume liquids, vapor release agents; the antiviral composition can be used for preventing and treating viral diseases selected from: rice dwarf, yellow dwarf, stripe disease, tomato fern leaf virus, pepper mosaic virus, tobacco vein necrosis virus, maize dwarf mosaic, cauliflower mosaic, citrus virus, cymbidium mosaic, cymbidium ringspot virus; the plant protected by the antiviral composition is selected from the following plants: rice, wheat, barley, oats, corn, sorghum, sweet potato, cassava, soybean, sweet broad bean, pea, mung bean, small bean, cotton, silkworm, peanut, rape, sesame, sunflower, sugar beet, sugarcane, coffee, cocoa, ginseng, fritillaria, rubber, coconut, oil palm, sisal, tobacco, tomato, chili, radish, cucumber, cabbage, celery, tuber mustard, sugar beet, rape, shallot, garlic, watermelon, melon, cantaloupe, papaya, apple, citrus and peach, tea, wild vegetables, bamboo shoots, hops, pepper, banana, papaya, orchid, bonsai.
Example 8: the application of the difluoropyrazole thiazole methanamide derivative I and the acaricide in preventing and treating the mite damage of agricultural, forestry and horticultural plants is as follows:
the difluoropyrazole thiazole methanamide derivative I and any one or two of commercial acaricides form an acaricidal composition for preventing and controlling acarid damages of agricultural and forestry and horticultural plants, wherein the commercial acaricides are selected from the following groups: dichlorvos, heptenophos, metofos, monocrotophos, phosphorus dibromide, pyrimidophos, chloromethylthion, ethion, chlorfenvinphos, vofenthion, pirimiphos, phoxim, isocarbophos, amicarbazone, chlormephos, fluthrin, bifenthrin, cyhalothrin, lambda-cyhalothrin, fenpropathrin, flumethrin, fluvalinate, bifenthrin, bifenazate, fenobucarb, butoxycarb, carbofuran, monocarb, benomyl, cloxacarb, butathiocarb, lufenuron, benzyl benzoate, bromopropylate, cyflumetofen, dimethrin, flufenpyr, fluazuron, bleomycin, chlortetracycline, abamectin, avermectin, lium, lividin, doramectin, epothidin, ivermectin, simethiofen, dimethofos, dimethrin, dimethoxim, fosetyl, chlorfenapyr, isofos, chlorfenapyr, dimethoxim, fluazurin, Nicotine, matrine, azadirachtin, rotenone, tebufenpyrad, pyridaben, fenpyroximate, clofentezine, propargite, hexythiazox, spirodiclofen, fluacrypyrim, propargite and pyridaben; the difluoropyrazole thiazole methanamide derivative I accounts for 1 to 90 percent of the total mass percentage of the acaricidal composition, and the ratio of the difluoropyrazole thiazole methanamide derivative I to the commercial acaricide accounts for 1 to 99 to 1 percent of the mass percentage; the acaricidal composition is processed into a dosage form selected from the following: seed treatment emulsions, aqueous emulsions, microemulsions, suspoemulsions, capsule suspensions, water soluble granules, fine granules, soluble concentrates, venoms, block baits, granular baits, tablet baits, concentrated baits, sustained release blocks, electrostatic sprays, oil-in-water emulsions, aerosol cans, aerosol candles, aerosol cartridges, aerosol sticks, aerosol tablets, aerosol pellets, gas generants, ointments, hot fogging formulations, cold fogging formulations, aerosols, solid/liquid mixtures, liquid/liquid mixtures, solid/solid mixtures, lacquers, microgranules, chasing powders, oil suspensions, oil dispersible powders, concentrated gels, pour-on formulations, seed coatings, paints, film-forming oils, ultra-low volume liquids, vapor release agents; the mite damage controlled by the mite-killing composition is selected from the following groups: the mite is selected from spider mite family, furaciidae, goiter family, Tetranychus genus, and pest mites of the goiter family, which are world agricultural pest mites, forestry pest mites, horticultural pest mites, and health pest mites; the plant for protecting the acaricidal composition is selected from the following plants: rice, wheat, barley, oats, corn, sorghum, sweet potato, cassava, soybean, sweet broad bean, pea, mung bean, small bean, cotton, silkworm, peanut, rape, sesame, sunflower, sugar beet, sugarcane, coffee, cocoa, ginseng, fritillaria, rubber, coconut, oil palm, sisal, tobacco, tomato, chili, radish, cucumber, cabbage, celery, tuber mustard, sugar beet, rape, shallot, garlic, watermelon, melon, cantaloupe, papaya, apple, citrus and peach, tea, wild vegetables, bamboo shoots, hops, pepper, banana, papaya, orchid, bonsai.
Industrial applicability
The invention provides difluoropyrazole thiazole formamide derivatives; the derivative can regulate and control the growth, development and damage of agricultural, horticultural and sanitary pests and plant pathogens of forestry plants, can be used for killing insects, killing mites, sterilizing, resisting plant viruses and inducing plants to generate disease resistance in the agricultural field, the horticultural field and the forestry field, and has better economic value and application prospect.
TABLE 2 bacteriostatic activity of difluoropyrazole thiazole carboxamide derivative I of the present invention (inhibition rate of 50. mu.g/ml/%)
| Serial number | Compound (I) | A.s | B.c | C.a | G.z | P.i | P.p | P.s | R.c | S.s |
| 1 | HZS-1-62 | 26 | 39 | 31 | 54 | 38 | 24 | 39 | 54 | 18 |
| 2 | HZS-1-89 | 19 | 86 | 29 | 46 | 33 | 22 | 45 | 67 | 64 |
| 3 | HZS-1-63 | 41 | 72 | 39 | 55 | 40 | 28 | 51 | 73 | 60 |
| 4 | HZS-1-82 | 41 | 50 | 42 | 66 | 33 | 27 | 40 | 71 | 80 |
| 5 | HZS-1-65 | 44 | 59 | 41 | 71 | 47 | 34 | 52 | 79 | 69 |
| 6 | HZS-1-81 | 34 | 46 | 31 | 63 | 40 | 32 | 46 | 82 | 80 |
| 7 | HZS-1-66 | 37 | 35 | 37 | 46 | 37 | 7 | 42 | 85 | 53 |
| 8 | HZS-1-90 | 42 | 34 | 42 | 45 | 37 | 45 | 51 | 89 | 82 |
| 9 | HZS-1-67 | 38 | 30 | 28 | 59 | 31 | 18 | 36 | 86 | 65 |
| 10 | HZS-1-83 | 32 | 42 | 34 | 64 | 27 | 24 | 38 | 87 | 62 |
| 11 | HZS-1-68 | 8 | / | 7 | 11 | 8 | 6 | 28 | 23 | 15 |
| 12 | HZS-1-84 | 37 | / | 34 | 55 | 48 | 21 | 54 | 91 | 82 |
| 13 | HZS-1-69 | 30 | / | 26 | 65 | 25 | 16 | 40 | 65 | 84 |
| 14 | HZS-1-85 | 44 | / | 37 | 28 | 33 | 14 | 40 | 83 | 94 |
| 15 | HZS-1-70 | 23 | / | 21 | 46 | 30 | 9 | 46 | 68 | 83 |
| 16 | HZS-1-86 | 34 | / | 39 | 59 | 33 | 21 | 39 | 82 | 83 |
| 17 | HZS-1-71 | 25 | / | 21 | 54 | 25 | 15 | 32 | 73 | 86 |
| 18 | HZS-1-87 | 25 | / | 22 | 46 | 25 | 11 | 35 | 51 | 67 |
| 19 | HZS-1-72 | 29 | / | 37 | 54 | 33 | 37 | 33 | 69 | 46 |
| 20 | HZS-1-88 | 29 | / | 28 | 38 | 28 | 6 | 23 | 26 | 69 |
| 21 | Fluxapyroxad | 74 | 100 | 86 | 41 | 13 | 48 | 15 | 41 | 83 |
| 22 | Thifluzamide | 65 | 59 | 82 | 35 | 13 | 39 | 15 | 56 | 88 |
/: not determined
A.s: tomato early blight, its latin name is: alternaria solani, b.c: the cucumber botrytis cinerea with the latin name as follows: botrytis cinerea, C.a: peanut brown spot pathogen, its latin name is: cercospora arachidicola, G.z: wheat scab, its latin name is: gibberella zeae, P.i: the late blight of potato, its latin name is: phytophthora infestans (Mont.) de barr, P.p: apple ring rot, its latin name is: physiosporia piricola, P.s: rhizoctonia solani, the Latin name of which is: pellicularia sasakii, R.c: rhizoctonia cerealis, with the latin name: rhizoctonia cere, S.s: sclerotinia sclerotiorum, its latin name is: sclerotina sclerotomalis.
Claims (7)
1. A difluoropyrazole thiazole carboxamide derivative is characterized by simultaneously containing difluoropyrazole and thiazole structures and having a structural general formula shown in a formula I:
wherein Het is selected from: thiazol-2, 4-yl, thiazol-4, 2-yl; r is selected from: phenyl, 2-chlorophenyl, 4-chlorophenyl, 2, 4-dichlorophenyl, 4-fluorophenyl, 4-methylphenyl, 4-trifluoromethylphenyl, 4-trifluoromethoxyphenyl; n is 2 to 4.
2. The specific synthetic route and method of difluoropyrazole thiazole carboxamide derivative I according to claim 1 are:
the definition of the substituent is as defined in claim 1, and the specific synthetic method comprises the following steps:
A. preparation of difluoropyrazole thiazolecarboxamide derivative I:
i is prepared by reacting intermediate difluoropyrazolothiazoformic acid, benzotriazol-1-yl-oxy-tripyrrolidinophosphonium hexafluorophosphate and N, N-diisopropylethylamine with substituted amine R- (CH) in dichloromethane solvent2)n-NH2Stirring at room temperature for reaction; the substituents are as defined in claim 1.
3. Use of the difluoropyrazole thiazole carboxamide derivative I as claimed in claim 1 for the preparation of agricultural fungicides.
4. An agricultural fungicidal composition comprising the difluoropyrazole thiazole carboxamide derivative I as claimed in claim 1 and an intermediate, which can be prepared as an agricultural fungicidal composition comprising the difluoropyrazole thiazole carboxamide derivative I as claimed in claim 1 as an active ingredient in an amount of 0.1 to 99.9% by weight, 99.9 to 0.1% by weight of a solid or liquid adjuvant, and optionally 0 to 25% by weight of a surfactant.
5. An agricultural sterilization compound composition, which comprises the difluoropyrazole thiazole carboxamide derivative I as claimed in claim 1 and other commercial bactericides as active ingredients, wherein the mass percentage of the difluoropyrazole thiazole carboxamide derivative I to the other commercial bactericides is 1 percent to 99 percent to 1 percent, the content of the active ingredients is 1 to 99 percent by weight, and the weight of the active ingredients is 99 to 1 percent of solid or liquid auxiliary agents.
6. An agricultural insecticidal and acaricidal compound composition, which comprises the difluoropyrazole thiazole carboxamide derivative I as claimed in claim 1 and other commercial insecticidal and acaricidal agents as active ingredients, wherein the mass percentage of the difluoropyrazole thiazole carboxamide derivative I to the other commercial insecticidal and acaricidal agents is 1% to 99% to 1%, the content of the active ingredients is 1 to 99% by weight, and 99 to 1% by weight of solid or liquid auxiliary agents.
7. A compound composition of an anti-plant virus agent, which comprises the difluoropyrazole thiazole carboxamide derivative I and other commercial anti-plant virus agents in the claim 1, wherein the proportions of the difluoropyrazole thiazole carboxamide derivative I and the other commercial anti-plant virus agents are 1 percent to 99 percent to 1 percent, the weight percentage of the active ingredients is 1 to 99 percent, and the weight percentage of the active ingredients is 99 to 1 percent of solid or liquid auxiliary agents.
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