CN116891466A - Pyrazole-containing dithiazole carboxamide derivative and preparation method and application thereof - Google Patents

Pyrazole-containing dithiazole carboxamide derivative and preparation method and application thereof Download PDF

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CN116891466A
CN116891466A CN202310905524.4A CN202310905524A CN116891466A CN 116891466 A CN116891466 A CN 116891466A CN 202310905524 A CN202310905524 A CN 202310905524A CN 116891466 A CN116891466 A CN 116891466A
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pyrazole
dithiazole
compound
carboxamide derivative
solution
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范志金
李坤
张越
于振武
洪泽宇
唐良富
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Nankai University
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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
    • 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
    • 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
    • A01N61/00—Biocides, pest repellants or attractants, or plant growth regulators containing substances of unknown or undetermined composition, e.g. substances characterised only by the mode of action
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01P—BIOCIDAL, PEST REPELLANT, PEST ATTRACTANT OR PLANT GROWTH REGULATORY ACTIVITY OF CHEMICAL COMPOUNDS OR PREPARATIONS
    • A01P1/00—Disinfectants; Antimicrobial compounds or mixtures thereof
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01P—BIOCIDAL, PEST REPELLANT, PEST ATTRACTANT OR PLANT GROWTH REGULATORY ACTIVITY OF CHEMICAL COMPOUNDS OR PREPARATIONS
    • A01P3/00—Fungicides
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01P—BIOCIDAL, PEST REPELLANT, PEST ATTRACTANT OR PLANT GROWTH REGULATORY ACTIVITY OF CHEMICAL COMPOUNDS OR PREPARATIONS
    • A01P7/00—Arthropodicides
    • A01P7/02—Acaricides
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01P—BIOCIDAL, PEST REPELLANT, PEST ATTRACTANT OR PLANT GROWTH REGULATORY ACTIVITY OF CHEMICAL COMPOUNDS OR PREPARATIONS
    • A01P7/00—Arthropodicides
    • A01P7/04—Insecticides
    • 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
    • C07D417/14—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 three or more hetero rings

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  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Environmental Sciences (AREA)
  • Zoology (AREA)
  • Pest Control & Pesticides (AREA)
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  • Organic Chemistry (AREA)
  • Engineering & Computer Science (AREA)
  • Wood Science & Technology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • General Health & Medical Sciences (AREA)
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  • Agronomy & Crop Science (AREA)
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Abstract

The invention provides a pyrazole-containing dithiazole carboxamide derivative, a preparation method and application thereof, in particular to a derivativeThe chemical structural general formula of the material is shown in formula I:

Description

Pyrazole-containing dithiazole carboxamide derivative and preparation method and application thereof
Technical Field
The technical scheme of the invention belongs to the field of pesticides, and particularly relates to a pyrazole-containing dithiazole carboxamide derivative, a preparation method and application thereof.
Background
Wheat is an important food crop in the world. As the population grows, so does the demand for wheat. However, wheat diseases not only affect the production of wheat, but also have a certain effect on the quality and commercial value of wheat, wherein wheat sheath blight is the main disease. In the prevention and treatment of wheat diseases, bactericides play an irreplaceable role. At present, the traditional wheat disease prevention and control pesticides are fewer, and the development of new pesticides is to solve the wheat disease and ensure the key break-through of wheat yield increase. The creation of new pesticides is an important guarantee for pesticide decrement and synergy in China. With the development of green ecological agriculture, the creation of green pesticides is a trend and challenge for the future development of pesticides (Shao Xusheng et al, world pesticides 2020, 42 (04): 16-24.).
Succinate Dehydrogenase (SDH) is an ideal bactericidal target, and SDH inhibitors exert their bactericidal activity by disrupting the mitochondrial tricarboxylic acid cycle and respiratory chain. SDHIs has been widely used to control botrytis cinerea and sclerotinia sclerotiorum, with a unique mechanism of action. Succinate dehydrogenase inhibitors (SDHIs) have been on the market successfully by carboxin (Earbox) developed by the United states patent Laiyaku in 1966. Since carboxin was marketed, succinic dehydrogenase inhibitor bactericides have been studied for three generations, have improved bioactivity and have expanded the bactericidal spectrum, and have become a very important class of bactericides (Zhang Yibin, world pesticides, 2007, 29 (1) 1-7). Boscalid, marketed in 2003, is an important milestone in the history of development of succinate dehydrogenase inhibitor-based fungicides, the first truly broad-spectrum succinate dehydrogenase inhibitor-based fungicides (Yan Fanyong, et al, pesticides, 2008, 47 (2): 132-135). Until 2009, the committee on the action of resistance to bactericides categorized such bactericides alone according to mechanism of action. To date, 24 SDHIs have been commercialized. Fungal resistance is developed due to prolonged or excessive application of SDHI bactericides. Therefore, new SDHIs without cross-resistance are always necessary in modern plant protection.
In order to find and discover pesticide lead and candidate compounds which are more efficient, broad-spectrum, low-toxicity and free of cross resistance, thiazole and difluoro pyrazole structures are combined, and a class of pyrazole-dithiazole carboxamide derivatives is designed and synthesized, so that an SDHI bactericide with high bactericidal activity is expected to be designed and synthesized. Therefore, based on the angles of reasonable design of pesticide molecules and creation of green pesticides, a series of pyrazole-contained thiazole carboxamide derivatives are designed and synthesized by adopting the principle of active structure splicing and the like, and the bactericidal activity of the system is evaluated.
Disclosure of Invention
The technical problems to be solved by the invention are as follows: provides a novel synthesis method of pyrazole-containing thiazole carboxamide derivatives, provides biological activities and determination methods of the compounds for regulating and controlling agricultural, horticultural and hygienic plant pests and plant pathogens in forestry, and simultaneously provides application of the compounds in the agricultural field, the horticultural field, the forestry field and the hygienic field.
The technical scheme adopted by the invention for solving the technical problems is as follows: the chemical structural general formula of the pyrazole-thiazole carboxamide derivative with insecticidal, acaricidal, bactericidal, anti-plant virus and induced plant disease resistance activity in the agricultural, horticultural and forestry fields is shown as I:
Wherein R is selected from: 1-isopropoxy-3-phenyl; 3-phenoxy-1-phenyl; 1,2,3, 4-tetrahydronaphthalen-5-yl; 2, 3-indan-4-yl; 1-naphthyl; 1- (tert-butyl) -3-phenyl; 2-bromo-3-methyl-1-phenyl; m-isopropylphenyl; 1,1' -biphenyl-3-yl; 4 '-chloro-1, 1' -biphenyl-2-yl; benzo [ d ] [1,3] diazol-4-yl; 1, 3-dibromo-5- (trifluoromethoxy) benzene-2-yl; 1, 3-dichloro-5- (trifluoromethoxy) benzene-2-yl; 1,3, 5-trichloro-2-yl; 1-bromo-3-methoxybenzene-5-yl; 2-bromo-1- (trifluoromethoxy) benzene-4-yl; 1-bromo-2- (trifluoromethyl) benzene-4-yl; 1-bromo-3-methoxybenzene-5-yl; 2-bromo-1-methoxybenzene-4-yl; 2-bromo-4- (trifluoromethyl) benzene-1-yl.
The synthesis route of the pyrazole-containing dithiazole carboxamide derivative I and the intermediate thereof is as follows:
the synthesis method of the pyrazole-containing dithiazole carboxamide derivative I comprises the following steps:
A. preparation of compound 2:
adding oxalyl chloride and N, N-dimethylformamide into the compound 1 and dichloromethane, after stirring reaction at room temperature, concentrating under reduced pressure, evaporating solvent, and diluting with dichloromethane; dropwise adding the dichloromethane solution of the residue into the 25% ammonia water solution of the single-neck round-bottom flask by using a constant-pressure dropping funnel under the ice bath condition, stirring overnight, and carrying out vacuum suction filtration to obtain a compound 2;
B. Preparation of compound 3:
adding 2 and Lawson reagents into a reaction bottle, dissolving in tetrahydrofuran solution, heating and refluxing, spotting a plate to judge that the reaction is finished, carrying out vacuum filtration, concentrating filtrate, and removing a solvent; dissolving and diluting with ethyl acetate, washing with saturated potassium carbonate solution, separating out water layer, and extracting with ethyl acetate; the combined organic layers were washed with saturated sodium chloride solution and dried over anhydrous sodium sulfate; vacuum filtering, concentrating the filtrate to remove solvent; purifying by petroleum ether/ethyl acetate eluent column chromatography to obtain compound 3;
C. preparation of Compound 4:
adding 3 into a reaction bottle, dissolving in ethanol, and dropwise adding ethyl bromopyruvate by using a syringe; heating and refluxing the mixed solution, carrying out reduced pressure suction filtration after the point plate monitoring reaction is finished, and concentrating filtrate to remove solvent; dissolving and diluting with ethyl acetate, washing with saturated sodium bicarbonate solution, separating out water layer, and extracting with ethyl acetate; the combined organic layers were washed with saturated sodium chloride solution and dried over anhydrous sodium sulfate; vacuum filtering, concentrating the filtrate to remove solvent, and purifying by petroleum ether/ethyl acetate eluent column chromatography to obtain compound 4;
D. preparation of compound 5:
adding 4 into a mixed solution of sodium hydroxide solution and ethanol in a single-neck round bottom flask, and gradually heating and refluxing; after the reaction is completed, pouring the reaction solution into a beaker, adjusting the pH of the solution by hydrochloric acid, and filtering to obtain a compound 5;
E. Preparation of Compound I:
adding 5, N-diisopropylethylamine into a reaction flask, dissolving in dichloromethane, and stirring at room temperature; after the solid is dissolved, adding benzotriazol-1-yl-oxy-tripyrrolidinyl phosphate hexafluorophosphate under ice bath condition, adding corresponding amine, stirring overnight at room temperature, washing with water after the reaction is finished, separating out an aqueous layer, extracting with dichloromethane, washing a combined organic layer with saturated sodium chloride solution, and drying with anhydrous sodium sulfate; vacuum filtering, concentrating the filtrate to remove solvent, and purifying with petroleum ether/ethyl acetate eluent column chromatography to obtain the corresponding product.
F. Use of pyrazole-containing dithiazole carboxamide derivatives I:
the invention provides the use of the pyrazole-containing dithiazole carboxamide derivatives I for the preparation of fungicides.
The invention provides application of pyrazole-containing dithiazole carboxamide derivative I in preparing tobacco mosaic virus resisting agents.
The invention provides application of pyrazole-containing dithiazole carboxamide derivative I in preparing a plant activator for inducing tobacco to resist tobacco mosaic virus.
The invention provides application of the pyrazole-containing dithiazole carboxamide derivative I in controlling insect pests of agricultural and forestry and horticultural plants.
G. Composition containing pyrazole dithiazole carboxamide derivative I and application thereof:
the pyrazole-containing dithiazole carboxamide derivative I is co-applied with an agrochemical; the agricultural chemical is selected from: one or more of insecticide, bactericide, plant virus resisting agent and acaricide.
The pyrazole-containing dithiazole carboxamide derivative I and any one or two of the pesticides are combined to form an insecticidal composition for controlling agricultural and forestry plant insect pests;
the insecticide is selected from: permethrin, ethofenprox, flumethrin, cyhalothrin, imidacloprid, nitenpyram imidaclothiz, thiacloprid, thiamethoxam, clothianidin, dinotefuran, collidine permethrin, ethofenprox, flumethrin, cyhalothrin, imidacloprid, nitenpyram, imidaclothiz, thiacloprid, thiamethoxam, clothianidin, dinotefuran, collidine, tolfenpyrad daphne, chlorfluazuron, polyfluorourea, flufenuron, bisfenuron fluazuron, oxazine, bistrifluron, furtebufenozide, tebufenozide, chlorfenozide, methomyl, chromafenozide, dichlorvos, quetiapine, pyridaphethione, leafhopper powder, carbaryl, pirimicarb, carbofuran, isoprocarb, cartap, fenobucarb, she Feisan, carbaryl, cartap, fenitrothion, hexythiazox, fenpyroximate, pyridaben, clofentezine, propargite, diafenthiuron, pymetrozine, spirodiclofen, spirotetramat, azocyclotin, buprofezin, monosultap, dimefon, chlorfenapyr, tetrachlorethamide, flufenamid, cyantraniliprole, chlorfenapyr, tolfenpyrad, pyrazinone, etoxazole, tebufenpyrad, flufenamid, pyridaben;
The mass percentage of the pyrazole-contained dithiazole carboxamide derivative I in the insecticidal composition is 1% -90%; preferably, the ratio of the pyrazole-containing dithiazole carboxamide derivative I to the pesticide is 1 percent to 99 percent by mass percent to 1 percent;
the formulation of the insecticidal composition is selected from the group consisting of: seed treatment emulsions, aqueous emulsions, microemulsions, suspoemulsions, capsule suspensions, water-soluble granules, fine granules, soluble concentrates, cereals, blocky baits, granular baits, sheeted baits, concentrated baits, slow release blocks, electrostatic sprays, oil-in-water emulsions, aerosol cans, aerosol candles, aerosol cans, aerosol sticks, aerosol flakes, aerosol pellets, aerosols, ointments, hot aerosols, cold aerosols, solid/liquid mixed packages, liquid/liquid mixed packages, solid/solid mixed packages, paint, microgranules, tracing powders, oil suspensions, oil dispersible powders, concentrated gels, sprinkles, seed coatings, spreads, film forming oils, ultra low volume liquids, vapor release agents;
the plant insect pest controlled by the insecticidal composition is selected from the group consisting of: spodoptera frugiperda, red spider, migratory locust, fomes officinalis, chinese rice locust, japanese Huang Jihuang, mole cricket, thrips oryzae, thrips tabaci, thrips pratensis, thrips oryzae, thrips katzenii, thrips mairei Jian Guan, white fly, bemisia tabaci, black tail leafhopper, dyer woad leaf hopper, cotton leafhopper, cerclage, brown planthopper, white-back planthopper, white planthopper, sugarcane horn planthopper, cotton aphid, wheat binary aphid, wheat long tube aphid, peach aphid sorghum aphid, radish aphid, meadow bug, sang Dun meadow bug, cerclage, meadow wax bug, red meadow bug, korean meadow bug, pear net bug, banana net bug, tendril bug, tiny flower bug, needle bug, red meadow bug, and red meadow bug the plant bug comprises Oryza sativa Linne, apolygus lucorum, hyriopsis schlegeli, hyriopsis sinensis, plutella xylostella, apolylis armyworm, phlebia xylostella, philippica armyworm, apolylis, apolytis sinensis, oryza sativa Linne, orthosiphon, and Orthosiphon moths, pink bollworms, sweet potato moths, plutella xylostellas, peach fruit borers, soybean fruit borers, apple leaf roller, brown leaf roller, yellow leaf roller, chilo suppressalis, pod borers, and corn borer, rice borer, cabbage borer, rice leaf roller, striped borer, cotton roll She Yeming, peach borer, armyworm, prodenia litura, rice borer fly, cotton budworm, beet armyworm, borer, cotton bollworm, ding point diamond-back, cotton bollworm, cotton boll moth, cotton bollworm, cotton boll moth, cotton tiger, cutworm, yellow cutworm, pirate, gypsy moth, sweet potato astromoth, bean astromoth, straight line rice butterfly, hidden line valley butterfly, citrus butterfly, yu bela butterfly, cabbage butterfly, ramie red vanado butterfly, ramie yellow vanado butterfly, bean genkwa, jin Xingbu nail, cuckoo beetle, ear beetle, ditch gold needle worm, fine chest gold needle worm, valley beetle, black bark beetle, citrus gill worm, jin Yuanji butcher, yellow meal worm, black meal worm, red-yellow larch, hybrid larch, copper green ali tortoise, dark black tortoise, giant black gill tortoise, mulberry longhorn, star longhorn, orange-brown longhorn, peach-red longhorn beetle, great ape leaf worm, small ape leaf worm, yellow-head melon, yellow-curved striped flea beetle, green bean image, pea image, broad bean image, corn image, rice image, wheat leaf bee, pear fruit bee, yellow-banded cornflower, armyworm white star-shaped hornet, bollworm cantilever, cotton bollworm tooth-lip hornet, borer black spot wart, mosquito, fly, tabanus, wheat red-absorbing plasmach, wheat Huang Xi thick beetle, rice gall midge, citrus fruit fly, melon fruit fly, wheat She Hui, american leaf fly, bean stalk black fly, wheat straw fly, seed fly, onion fly, radish fly, umbrella-skirt, corn borer, myza fly, and insect;
The plants controlled by the insecticidal composition are selected from the group consisting of: rice, wheat, barley, oat, corn, sorghum, sweet potato, tapioca, soybean, netherlands, broad bean, pea, mung bean, cotton, mulberry, peanut, canola, sesame, sunflower, sugar beet, sugarcane, coffee, cocoa, ginseng, fritillaria, rubber, coconut, oil palm, sisal, tobacco, tomato, chilli, radish, cucumber, cabbage, celery, mustard, beet, rape, onion, garlic, watermelon, melon, cantaloupe, papaya, apple, citrus and peach, tea, wild herbs, bamboo shoots, hops, peppers, banana, papaya, orchid, bonsai.
The composition containing the pyrazole dithiazole carboxamide derivative I and any one or two of the bactericides is used for preventing and controlling plant diseases of agriculture, forestry and gardening;
the bactericide is selected from the group consisting of: benzothiadiazole, tiadinil, mefenamide, DL-beta-aminobutyric acid, isotiadinil, ribavirin, antofine, ningnanmycin or salicylic acid, cymoxanil, thiram, ziram, mancozeb, fosetyl-aluminum, thiophanate-methyl, chlorothalonil, cortisone, procymidone, fenpropidin, thiophanate-methyl, metalaxyl-M, flumorph, dimethomorph, high-efficiency metalaxyl, high-efficiency benalaxyl, dicyclopentadienyl-amine Sulfosamine, methanesulfonamide, thiaflufenamid, phyllostatin, cyclopropylamide, cycloflufenamid, cycloxaprid, cyromazine, silthiopham, carboxin, mefloxamide, mefenamid, flufenamid, furazamide, thifluzamide, boscalid, pyrimethanil, boscalid, isopyrazam, bixafen, fluopyram, epoxiconazole, fluxapyroxad, fluxad penflufen, ipratropium, fluoxastrobin amide, fluocinolone acetonide, mandipropamid, zoxamide, ethirimol, iprodione, azoxystrobin, dimoxystrobin, fluoxastrobin, trifloxystrobin, and other drugs kresoxim-methyl, phenoxymycylamine, trifloxystrobin, picoxystrobin, pyraclostrobin, trifloxystrobin, enestroburin, epoxiconazole, furfuryl, cyproconazole, difenoconazole, diniconazole, cyproconazole, trifloxystrobin, and trifloxystrobin kresoxim-methyl, phenoxymycylamine, orysastrobin, picoxystrobin, pyraclostrobin, trifloxystrobin, enoxystrobin, trifloxystrobin, pyraclostrobin, trifloxystrobin, the composition comprises the components of the alkene oxime amine, the epoxiconazole, the furfuryl myclobutanil, the cyproconazole, the difenoconazole, the diniconazole, famoxadone, boscalid, hymexazol, oxadixyl, ethaboxam, hymexazol, xin Sai ketone, benzothiophene, dodemorph, fenpropimorph, tridemorph, fenpiclonil, fludioxonil, fluazinam, pyripyroxime, cyprodinil, fluoxastrobin, boscalid, cyprodinil, fluoxastrobin, thifluzamide, cyprodinil, pyrimethanil, pyribenzoxim, flubenomyl, fenamidone, dithianon ethoxyquin, hydroxyquinoline, propoxyquinoline, phenoxyquinoline, diethofencarb, iprovalicarb, benthiavalicarb, propamocarb, sulfencarb, diphenfos, iprobenfos, pirimiphos, tolclofos-methyl, blasticidin, kasugamycin, polyoxin, validamycin, streptomycin, metalaxyl, furalaxyl, benalaxyl, furalaxyl, carbendazim, benomyl, thiophanate-methyl triazolone, bupirimate, dimethirimol, ethirimol, captan, folpet, ethephon, fluocinolone, dimethachlon, chlorothalonil, trifloxystrobin, isoprothiolane, metrafenib, propineb, fosetyl-aluminum, sulfur, bordeaux, copper sulfate, cupric oxychloride, cuprous oxide, cupric hydroxide, metrafenone, pencycuron, pyridazone, tetrachlorophthalein, fluquindoxazone, spiroxamine, tricyclazole, zinone, dodine, biguanide, octopamide, chloronitramine, benomyl, tosulfamide, indolyl, sodium disulzin, quizalofoone, probenazole, bronopol, methyl iodide, carb, dixyl, dazomet, dichloroisopropyl, triclophos, fenphos, methoprene, triazophos, thiofluoride, dichloroprop, dichlorvos, isoprothiazole;
The total mass percentage of the pyrazole-containing dithiazole carboxamide derivative I in the bactericidal composition is 1% -90%; the ratio of the pyrazole-contained dithiazole carboxamide derivative I to the bactericide is 1 to 99 to 1 percent by mass percent;
the dosage form of the bactericidal composition is selected from the group consisting of: seed treatment emulsions, aqueous emulsions, microemulsions, suspoemulsions, capsule suspensions, water-soluble granules, fine granules, soluble concentrates, cereals, blocky baits, granular baits, sheeted baits, concentrated baits, slow release blocks, electrostatic sprays, oil-in-water emulsions, aerosol cans, aerosol candles, aerosol cans, aerosol sticks, aerosol flakes, aerosol pellets, aerosols, ointments, hot aerosols, cold aerosols, solid/liquid mixed packages, liquid/liquid mixed packages, solid/solid mixed packages, paint, microgranules, tracing powders, oil suspensions, oil dispersible powders, concentrated gels, sprinkles, seed coatings, spreads, film forming oils, ultra low volume liquids, vapor release agents;
the plant diseases controlled by the bactericidal composition are selected from the group consisting of: seedling blight, tomato root rot, potato late blight, tobacco black shank, millet powdery mildew, grape downy mildew, lettuce downy mildew, cucumber anthracnose;
Plants for which the fungicidal composition is suitable are selected from: rice, wheat, barley, oat, corn, sorghum, sweet potato, tapioca, soybean, netherlands, broad bean, pea, mung bean, cotton, mulberry, peanut, canola, sesame, sunflower, sugar beet, sugarcane, coffee, cocoa, ginseng, fritillaria, rubber, coconut, oil palm, sisal, tobacco, tomato, chilli, radish, cucumber, cabbage, celery, mustard, beet, rape, onion, garlic, watermelon, melon, cantaloupe, papaya, apple, citrus and peach, tea, wild herbs, bamboo shoots, hops, peppers, banana, papaya, orchid, bonsai.
The pyrazole-containing dithiazole carboxamide derivative I and any one or two of the antiviral agents are combined to form an antiviral composition for preventing and treating viral diseases of agricultural and forestry plants and horticultural plants;
the antiviral agent is selected from: benzothiadiazole, tiadinil, isotiadinil DL- β -aminobutyric acid, 2, 6-dichloroisonicotinic acid, N-cyanomethyl-2-chloroisonicotinamide, allylisothiazole, ribavirin, antofine, ningnanmycin, methiadipamide or salicylic acid, pyrimidomycin, dichloroisonicotinic acid, allylisothiazole, validamycin, moroxydine hydrochloride;
The total mass percentage of the pyrazole-containing dithiazole carboxamide derivative I in the antiviral composition is 1% -90%; preferably, the ratio of the pyrazole-containing dithiazole carboxamide derivative I to the plant virus resisting agent is 1 to 99 to 1 percent by mass;
the antiviral composition is formulated in 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, cereals, blocky baits, granular baits, sheeted baits, concentrated baits, slow release blocks, electrostatic sprays, oil-in-water emulsions, aerosol cans, aerosol candles, aerosol cans, aerosol sticks, aerosol flakes, aerosol pellets, aerosols, ointments, hot aerosols, cold aerosols, solid/liquid mixed packages, liquid/liquid mixed packages, solid/solid mixed packages, paint, microgranules, tracing powders, oil suspensions, oil dispersible powders, concentrated gels, sprinkles, seed coatings, spreads, film forming oils, ultra low volume liquids, vapor release agents;
the virus diseases prevented and treated by the antiviral composition are selected from the following: rice dwarf, yellow dwarf, stripe disease, tomato fern leaf virus, pepper mosaic virus, tobacco vein necrosis virus, maize dwarf mosaic, cauliflower mosaic virus, citrus virus, cymbidium mosaic virus, cymbidium ringspot virus;
The plants for which the antiviral composition is used for control are selected from: rice, wheat, barley, oat, corn, sorghum, sweet potato, tapioca, soybean, netherlands, broad bean, pea, mung bean, cotton, mulberry, peanut, canola, sesame, sunflower, sugar beet, sugarcane, coffee, cocoa, ginseng, fritillaria, rubber, coconut, oil palm, sisal, tobacco, tomato, chilli, radish, cucumber, cabbage, celery, mustard, beet, rape, onion, garlic, watermelon, melon, cantaloupe, papaya, apple, citrus and peach, tea, wild herbs, bamboo shoots, hops, peppers, banana, papaya, orchid, bonsai.
The acaricidal composition formed by the combination of the pyrazole-contained thiazole carboxamide derivative I and any one or two of the acaricides is used for controlling the acarid of agricultural and forestry and horticultural plants;
the acaricide is selected from the group consisting of: dichlorvos, heptylphosphines, fast-acting phoxims, dibromophoxims, pyrimidophos, chlormethiphos, ethion, chlorfenphos, valphos, methyl pyrimidothioate, quetiaphos, triazamate, chlorpyrifos, fenphos, flumethrin, bifenthrin, cyhalothrin, lambda-cyhalothrin, fenpropathrin, flumethrin, cyfluthrin, bromfluthrin, bifenazate, benfuracarb, butanone, carbofuran, mefenoxam, benomyl, chlormefos, ding Liusu carbofuran acarb, benzyl benzoate, bromopropylate, cyflumetofen, chloranil, flumetofen, flufenoxuron, liuyangmycin, chongmycin, thuringiensis, acaricide, liuyangmycin, avermectin, doramectin, eprinomectin, ivermectin, siramectin, moxidectin, pyrethrin, nicotine, matrine, azadirachtin, rotenone, tebufenpyrad, pyridaben, fenpyroximate, clofentezine, propargite, hexythiazox, spirodiclofen, azoxystrobin, acaricide, clofentezine;
The total mass percentage of the pyrazole-containing dithiazole carboxamide derivative I in the acaricidal composition is 1% -90%; the ratio of the pyrazole-contained dithiazole carboxamide derivative I to the acaricide is 1 to 99 to 1 percent by mass percent;
the formulation of the acaricidal composition is selected from the group consisting of: seed treatment emulsions, aqueous emulsions, microemulsions, suspoemulsions, capsule suspensions, water-soluble granules, fine granules, soluble concentrates, cereals, blocky baits, granular baits, sheeted baits, concentrated baits, slow release blocks, electrostatic sprays, oil-in-water emulsions, aerosol cans, aerosol candles, aerosol cans, aerosol sticks, aerosol flakes, aerosol pellets, aerosols, ointments, hot aerosols, cold aerosols, solid/liquid mixed packages, liquid/liquid mixed packages, solid/solid mixed packages, paint, microgranules, tracing powders, oil suspensions, oil dispersible powders, concentrated gels, sprinkles, seed coatings, spreads, film forming oils, ultra low volume liquids, vapor release agents;
the mite injury prevented and controlled by the mite-killing composition is selected from the following components: the mites are selected from the group consisting of spider mites, tetranychidae, furwire mites, goiter mites, red spider mites, goiter mites, said mites being world-wide agricultural, forestry, horticultural and hygiene mites;
The plants for which the acaricidal composition is used for control are selected from the group consisting of: rice, wheat, barley, oat, corn, sorghum, sweet potato, tapioca, soybean, netherlands, broad bean, pea, mung bean, cotton, mulberry, peanut, canola, sesame, sunflower, sugar beet, sugarcane, coffee, cocoa, ginseng, fritillaria, rubber, coconut, oil palm, sisal, tobacco, tomato, chilli, radish, cucumber, cabbage, celery, mustard, beet, rape, onion, garlic, watermelon, melon, cantaloupe, papaya, apple, citrus and peach, tea, wild herbs, bamboo shoots, hops, peppers, banana, papaya, orchid, bonsai.
The bioactivity of the pyrazole-containing dithiazole carboxamide derivative I is determined as follows:
the bactericidal activity of the pyrazole-thiazole carboxamide derivative I is measured:
the bactericidal or bacteriostatic activity of the pyrazole-thiazole carboxamide derivative I is determined by a thallus growth rate assay method, and the method comprises the following specific steps: 1.8 mg of sample is dissolved in 2 drops of dimethyl sulfoxide, then the sample is diluted to 500 micrograms/ml of medicament by using an aqueous solution containing a certain amount of Tween 20 emulsifier, 1 ml of medicament to be tested is respectively sucked into a culture dish under the aseptic condition, 9 ml of PDA culture medium is respectively added, 50 micrograms/ml of medicament-containing flat plate is prepared after shaking uniformly, 1 ml of sterilized water is added to serve as blank control, a bacterial dish is cut along the outer edge of hypha by using a puncher with the diameter of 4 mm, the bacterial dish is moved to the medicament-containing flat plate to be placed in an equilateral triangle, each treatment is repeated for 3 times, the culture dish is placed in a constant temperature incubator with the temperature of 24+/-1 ℃ for culture, the expansion diameter of each bacterial dish is investigated after the diameter of a control colony is expanded to 2-3 cm, the average value is calculated, and the relative antibacterial rate is compared with the blank control, and the bacterial is the species of most of typical plant pathogenic bacteria actually generated in fields in agricultural production in China, and the code and name is as follows: a.s: the Latin name of the early blight bacteria of tomato is: alternaria solani, b.c: the Latin name of the Botrytis cinerea is: botrytis cinerea, C.a: peanut brown spot germ, its latin name is: cercospora arachidicola, F.g: fusarium graminearum, its Latin name is: fusarium graminearum, F.v: fusarium verticillium, the Latin name of which is: fusarium verticillioides, P.p: apple ring rot germ, its latin name is: physalospora piricola, R.c: rhizoctonia cerealis, its Latin name is: rhizoctonia cerealis, R.s: rhizoctonia solani, its Latin name is: rhizoctonia solani, S.s: sclerotinia sclerotiorum, the Latin name of which is: sclerotinia sclerotiorum.
The beneficial effects of the invention are as follows: leading optimization is carried out on the pyrazole-contained dithiazole carboxamide derivative I, and antibacterial activity screening is carried out on the pyrazole-contained dithiazole carboxamide derivative I.
The synthesis and biological activity and use of the pyrazole-containing dithiazole carboxamide derivatives I are more specifically illustrated by specific preparation and biological activity assay examples, which are provided solely for the purpose of illustrating the invention and not for the purpose of limiting the same, in particular the biological activity is provided solely for the purpose of illustrating the invention and not for the purpose of limiting the same, as follows:
example 1: preparation of Compound I-4:
(1) 1 (10.00 g, 56.78 mmol) and 100 ml of dichloromethane were added to a 250 ml single neck round bottom flask, oxalyl chloride (9.7 ml, 113.56 mmol) and 3 drops of N, N-dimethylformamide were added dropwise to the 1 dichloromethane solution and stirred at room temperature for 30 minutes. After the reaction, the solution was yellow and transparent, the solvent was evaporated under reduced pressure, and diluted with dichloromethane. A dichloromethane solution of 3- (difluoromethyl) -1-methyl-1H-pyrazole-4-carbonyl chloride was added dropwise to a 25% aqueous ammonia solution (15.44 g, 227.12 mmol) in a 250 ml single-neck round bottom flask with a constant pressure dropping funnel under ice-bath conditions, and stirred overnight to give a white solid. Suction filtration under reduced pressure gave 9.74 g of the product as a white solid with a yield of 98%.
(2) 2 (5.00 g, 28.55 mmol) and Lawson's reagent (6.93 g, 17.13 mmol) were added to a 100 ml single neck round bottom flask, dissolved in 30 ml tetrahydrofuran solution, heated to reflux at 60℃for 30 minutes, and the reaction was judged to be complete by spotting. After the reaction was completed, suction filtration was performed under reduced pressure, and the filtrate was concentrated to remove the solvent. The mixture was diluted with 20 ml of ethyl acetate, washed twice with 20 ml of saturated potassium carbonate solution, and the aqueous layer was separated and extracted twice with 10 ml of ethyl acetate. The combined organic layers were washed once with 10 ml of saturated sodium chloride solution and dried over anhydrous sodium sulfate. Vacuum filtering, concentrating filtrate to remove solvent. Purification by column chromatography with petroleum ether/ethyl acetate=2:1 (volume ratio) eluent afforded product 3 as a yellow solid. The yield was 5.01 g and 92%.
(3) Into a 50 ml two-neck round bottom flask was added 3 (0.50 g, 2.62 mmol) dissolved in 20 ml ethanol and ethyl bromopyruvate (0.45 ml, 2.88 mmol) was added dropwise with a syringe. The mixed solution was heated to reflux at 80 degrees celsius for 2 hours and the reaction was monitored by spot-plating. After the reaction was completed, suction filtration was performed under reduced pressure, and the filtrate was concentrated to remove the solvent. The mixture was diluted with 20 ml of ethyl acetate, washed twice with 10 ml of saturated sodium bicarbonate solution, and the aqueous layer was separated and extracted twice with 10 ml of ethyl acetate. The combined organic layers were washed once with 10 ml of saturated sodium chloride solution and dried over anhydrous sodium sulfate. Vacuum filtration, concentration of the filtrate to remove solvent, column chromatography purification with petroleum ether/ethyl acetate=2:1 (volume ratio) eluent gave 4 as a beige solid in a yield of 0.87 g and 86%.
(4) Into a 250 ml single neck round bottom flask was added 4 (4.02 g, 13.99 mmol) in 80 ml of a mixed solution of 2 mol per liter sodium hydroxide and 15 ml ethanol, which was gradually heated to 80 degrees celsius and refluxed for 30 minutes. The reaction was completed and a yellow clear solution was obtained. The reaction was cooled to room temperature, the reaction solution was poured into a 250 ml beaker, the ph=2 of the solution was adjusted with 2 mol per liter of hydrochloric acid, and the solution was filtered to give a beige solid 5 in a yield of 3.28 g and a yield of 91%.
(5) Into a 50 ml single neck round bottom flask was added 5 (0.10 g, 0.39 mmol) and N, N-diisopropylethylamine (0.13 ml, 0.77 mmol), dissolved in dichloromethane and stirred at room temperature. After dissolution of the solid, benzotriazol-1-yl-oxy-tripyrrolidinylphosphine hexafluorophosphate (0.22 g, 0.42 mmol) was added under ice-bath conditions, after stirring for 15 minutes, 3-isopropoxyaniline (62 μl, 0.39 mmol) was added, stirring overnight at room temperature, after completion of the reaction, the aqueous layer was separated and extracted twice with 5 ml of dichloromethane, the organic layer was combined, washed once with 10 ml of saturated sodium chloride solution, and dried over anhydrous sodium sulfate. Vacuum filtering, concentrating the filtrate to remove solvent, and purifying with petroleum ether/ethyl acetate 2:1 (volume ratio) eluent column chromatography to obtain compound I with yield of 0.145 g and 95%
Example 2: the antibacterial activity measurement result of the pyrazole dithiazole carboxamide derivative I:
the codes and names of the common plant pathogenic fungi tested by the invention are as follows: a.s: the Latin name of the early blight bacteria of tomato is: alternaria solani, b.c: the Latin name of the Botrytis cinerea is: botrytis cinerea, C.a: peanut brown spot germ, its latin name is: cercospora arachidicola, F.g: fusarium graminearum, its Latin name is: fusarium graminearum, F.v: fusarium verticillium, the Latin name of which is: fusarium verticillioides, P.p: apple ring rot germ, its latin name is: physalospora piricola, R.c: rhizoctonia cerealis, its Latin name is: rhizoctonia cerealis, R.s: rhizoctonia solani, its Latin name is: rhizoctonia solani, S.s: sclerotinia sclerotiorum, the Latin name of which is: sclerotinia sclerotiorum. These species are well representative and can represent the species of most pathogenic bacteria occurring 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 with different degrees at 50 micrograms/milliliter; commercial thifluzamide is the most closely related commercial germicide to the chemical structure of the present patent. The invention uses thifluzamide as positive control to carry out the determination of the biological activity of the novel compound; the results show that: for the gray mold bacteria of cucumber, the bactericidal activity of the compounds I-1, I-2, I-4, I-5, I-7, I-9, I-10 and I-12 is above 60%, wherein the inhibition rate of the compounds I-4 and I-9 reaches 80%, and the inhibition rate of the control thifluzamide is 59%; for fusarium graminearum, the inhibition rates of the compounds I-4, I-6, I-8, I-9, I-10 and I-12 are all above 50%, and especially the bactericidal activity of the compound I-8 is 73% respectively and is higher than that of a positive control drug thifluzamide by 35%; for Fusarium verticillium, the inhibition rates of the compounds I-2, I-4, I-5 and I-7 are all above 30%, which is higher than that of a positive control medicine thifluzamide by 22%; for apple ring rot, the bactericidal activity of the compound I-5 is 47% and is higher than that of a positive control drug thifluzamide by 39%; for the Rhizoctonia cerealis, the inhibition rates of the compounds I-4, I-5 and I-9 are above 50%, and the positive control drug thifluzamide is 56%; for Rhizoctonia solani, the bactericidal activity of the compounds I-1, I-2, I-4, I-5, I-7 and I-9 is above 50%, and the reference thifluzamide is 85%. In conclusion, the compounds I-4, I-5 and I-9 show higher bactericidal activity.
Example 3: the invention relates to application of pyrazole-containing dithiazole carboxamide derivative I in preparation of pesticide composition:
the pyrazole-contained dithiazole carboxamide derivative I of the invention is used for preparing pesticide compositions, the compositions contain the pyrazole-contained dithiazole carboxamide derivative I of the invention and intermediates thereof as active ingredients, the mass percent of the active ingredients is 0.1 to 99.9 percent, the mass percent of solid or liquid auxiliary agents is 99.9 to 0.1 percent, and the compositions further contain surfactant which is optionally 0 to 50 mass percent.
Example 4: the invention relates to application of pyrazole-containing dithiazole carboxamide derivative I in preparing pesticide compound compositions:
the pyrazole-containing dithiazole carboxamide derivative I and the intermediate thereof can be compounded with other commodity pesticides, namely, insecticides, acaricides, bactericides, antiviral agents or plant activators to prepare pesticide compound compositions, the compound compositions comprise the pyrazole-containing dithiazole carboxamide derivative I and the intermediate thereof and the commodity pesticides, namely, the insecticides, acaricides, bactericides, antiviral agents or plant activators as active ingredients, and the ratio of the pyrazole-containing dithiazole carboxamide derivative I and the intermediate thereof to the other commodity pesticides, namely, the insecticides, acaricides, bactericides, antiviral agents or plant activators is 1% -99% -1% by mass, the mass percentage of the active ingredients is 0.1% -99.9%, the mass percentage of the solid or liquid auxiliary agents is 99.9% -0.1% by mass percentage, and the surfactant is optionally 0% -50% by mass percentage.
Example 5: the application of the pyrazole-containing dithiazole carboxamide derivative I and the pesticide combination in controlling insect pests of agricultural and forestry and horticultural plants:
the insecticidal composition formed by combining any one or two of pyrazole-contained thiazole carboxamide derivatives I and commercial insecticide is used for preventing and controlling insect pests of agriculture, forestry and horticulture plants, wherein the commercial insecticide is selected from the following components: permethrin, ethofenprox, flumethrin, cyfluthrin, imidacloprid, nitenpyram imidaclothiz, thiacloprid, thiamethoxam, clothianidin, dinotefuran, clonidine, daphne permethrin, ethofenprox, flumethrin, fluvalinate, imidacloprid, nitenpyram, imidaclothiz, thiacloprid, thiamethoxam, clothianidin, dinotefuran, clonidine, danadzum diflubenzuron, chlorbenzuron, chlorfluazuron, lufenuron, chlorfluazuron, novaluron, polyfluofluazuron, flucycloxuron, bisfenuron fluazuron, oxazine, bistrifluron, furtebufenozide, tebufenozide, chlorfenozide, methomyl, chromafenozide, dichlorvos, quetiapine, pyridaphethione, leafhopper powder, carbaryl, pirimicarb, carbofuran, isoprocarb, cartap, fenobucarb, she Feisan, carbaryl, cartap, fenitrothion, hexythiazox, fenpyroximate, pyridaben, clofentezine, propargite, diafenthiuron, pymetrozine, spirodiclofen, spirotetramat, azocyclotin, buprofezin, monosultap, dimefon, chlorfenapyr, tetrachlorethamide, flufenamid, cyantraniliprole, chlorfenapyr, tolfenpyrad, pyrazinone, etoxazole, tebufenpyrad, flufenamid, pyridaben; the mass percentage of the pyrazole-containing dithiazole carboxamide derivative I in the insecticidal composition is 1% -90%, and the mass percentage of the pyrazole-containing dithiazole carboxamide derivative I to the commercial insecticide is 1% -99% -1%; the formulation of the insecticidal composition is selected from the group consisting of: seed treatment emulsions, aqueous emulsions, microemulsions, suspoemulsions, capsule suspensions, water-soluble granules, fine granules, soluble concentrates, cereals, blocky baits, granular baits, sheeted baits, concentrated baits, slow release blocks, electrostatic sprays, oil-in-water emulsions, aerosol cans, aerosol candles, aerosol cans, aerosol sticks, aerosol flakes, aerosol pellets, aerosols, ointments, hot aerosols, cold aerosols, solid/liquid mixed packages, liquid/liquid mixed packages, solid/solid mixed packages, paint, microgranules, tracing powders, oil suspensions, oil dispersible powders, concentrated gels, sprinkles, seed coatings, spreads, film forming oils, ultra low volume liquids, vapor release agents; the plant insect pest for which the insecticidal composition is suitable is selected from the group consisting of: spodoptera frugiperda, red spider, migratory locust, fomes officinalis, chinese rice locust, japanese Huang Jihuang, mole cricket, thrips oryzae, thrips tabaci, thrips pratensis, thrips oryzae, thrips katzenii, thrips mairei Jian Guan, white fly, bemisia tabaci, black tail leafhopper, dyer woad leaf hopper, cotton leafhopper, cerclage, brown planthopper, white-back planthopper, white planthopper, sugarcane horn planthopper, cotton aphid, wheat binary aphid, wheat long tube aphid, peach aphid sorghum aphid, radish aphid, meadow bug, sang Dun meadow bug, cerclage, meadow wax bug, red meadow bug, korean meadow bug, pear net bug, banana net bug, tendril bug, tiny flower bug, needle bug, red meadow bug, and red meadow bug the plant bug comprises Oryza sativa Linne, apolygus lucorum, hyriopsis schlegeli, hyriopsis sinensis, plutella xylostella, apolylis armyworm, phlebia xylostella, philippica armyworm, apolylis, apolytis sinensis, oryza sativa Linne, orthosiphon, and Orthosiphon moths, pink bollworms, sweet potato moths, plutella xylostellas, peach fruit borers, soybean fruit borers, apple leaf roller, brown leaf roller, yellow leaf roller, chilo suppressalis, pod borers, and corn borer, rice borer, cabbage borer, rice leaf roller, striped borer, cotton roll She Yeming, peach borer, armyworm, prodenia litura, rice borer fly, cotton budworm, beet armyworm, borer, cotton bollworm, ding point diamond-back, cotton bollworm, cotton boll moth, cotton bollworm, cotton boll moth, cotton tiger, cutworm, yellow cutworm, pirate, gypsy, sweet potato astromoth, bean astromoth, straight line rice butterfly, hidden line valley butterfly, citrus phoenix butterfly, yu bel phoenix butterfly, cabbage butterfly, ramie red vanity butterfly, ramie yellow vanity butterfly, bean genkwa, jin Xingbu nail, cuckoo-bark beetle, ear beetle, ditch needle worm, fine chest needle worm, valley bark beetle, black bark beetle, citrus gill worm, jin Yuanji butcher, yellow meal worm, black meal worm, red-yellow larch, hybrid larch, copper green ali tortoise, dark black tortoise, giant black gill tortoise, mulberry longhorn, star longhorn, orange-brown longhorn, peach-red longhorn beetle, great ape leaf worm, small ape leaf worm, yellow-head melon, yellow-curved striped flea beetle, green bean image, pea image, broad bean image, corn image, rice image, wheat leaf bee, pear fruit bee, yellow-banded cornflower, armyworm white star-shaped hornet, bollworm cantilever, cotton bollworm tooth-lip hornet, borer black spot wart, mosquito, fly, tabanus, wheat red-absorbing plasmach, wheat Huang Xi thick beetle, rice gall midge, citrus fruit fly, melon fruit fly, wheat She Hui, american leaf fly, bean stalk black fly, wheat straw fly, seed fly, onion fly, radish fly, umbrella-skirt, corn borer, myza fly, and insect; plants to which the insecticidal composition is applicable are selected from: rice, wheat, barley, oat, corn, sorghum, sweet potato, tapioca, soybean, netherlands, broad bean, pea, mung bean, cotton, mulberry, peanut, canola, sesame, sunflower, sugar beet, sugarcane, coffee, cocoa, ginseng, fritillaria, rubber, coconut, oil palm, sisal, tobacco, tomato, chilli, radish, cucumber, cabbage, celery, mustard, beet, rape, onion, garlic, watermelon, melon, cantaloupe, papaya, apple, citrus and peach, tea, wild herbs, bamboo shoots, hops, peppers, banana, papaya, orchid, bonsai.
Example 6: the application of the pyrazole-containing dithiazole carboxamide derivative I and the bactericide composition in preventing and controlling agricultural and forestry and gardening plant diseases:
the bactericidal composition is formed by combining any one or two of pyrazole-thiazole carboxamide derivatives I and commercial bactericides, and is used for preventing and controlling plant diseases of agriculture, forestry and gardening, wherein the commercial bactericides are selected from the following group: benzothiadiazoles, tiadinils, mefenacets, isotiadinils, ribavirin, antofine, ningnanmycin or salicylic acid, cymoxanil, thiram, ziram, mancozeb, fosetyl-aluminum, thiophanate-methyl, chlorothalonil, prednisone, procymidone, fenpropidin, thiophanate-methyl, metalaxyl-M, flumorph, dimethomorph, high-efficiency metalaxyl, high-efficiency benalaxyl, mechlorethamine, sulfenamid methanesulfonamide, thiabendazole, leaf-carrier, cyclopropylamide, cyflufenamid, cycloxaprid, fenhexamid, silthiopham, carboxin, mefloxuron, formamide, mechlorethamine, flufenamid, fenhexamid, fenpyrad-ethyl, fenpyrad, fenpyralimid, flux, cyx, furametpyr, thifluzamide, boscalid, penthiopyrad, isopyrazam, bixafen, fluopyram, cyproconazole, fluxapyroxad, penflufen Isoprothiazamine, fluxapyroxad hydroxylamine, fluoxyfen amide, fluocinolide, mandipropamid, zoxamide, ethaboxam, iprodione, azoxystrobin, dimoxystrobin, fluoxastrobin, kresoxim-methyl, trifloxystrobin, picoxystrobin, pyraclostrobin, trifloxystrobin, enoximate, enoximide, epoxiconazole, furfuryl, cyproconazole, difenoconazole, diniconazole, high-efficiency diniconazole, epoxiconazole fenbuconazole, fluquinconazole, flusilazole, flutriafol, hexaconazole, imibenconazole, ipconazole, metconazole, myclobutanil, penconazole, propiconazole, prothioconazole, simeconazole, tebuconazole, triadimenol, myclobutanil, penconazole, propiconazole, and penconazole, and tebuconazole, respectively, and the like sterilizing azole, bitertanol, thiabendazole, corncob-tannin, imazalil, high-efficiency imazalil, prochloraz, triflumizole, cyazofamid, imidazolone, oxdiazole, fenoxanil, famoxadone, boscalid, pyribenzoxim, prochloraz, fenbuconazole, fenpican, fenbuconazole, and other active compounds, hymexazol, oxadixyl, ethaboxam, hymexazol, xin Sai ketone, benthiavalicarb-isopropyl, dode-morph, fenpropimorph, tridemorph, fenpiclonil, fluazinam, pyripyroxime, cyprodinil, fluoxastrobin, cyprodinil, fluoxastrobin, thifluzamide, cyprodinil, pyrimethanil, pyribenzoxim, flubenyrimidine alcohol, fenamic, dithianon, ethoxyquinoline, hydroxyquinoline propiquin, phenoxyquinoline, diethofencarb, iprovalicarb, benthiavalicarb, propamocarb, fenoxanil, iprobenfos, pyraclostrobin, tolclofos-methyl, blasticidin, kasugamycin, polyoxin, validamycin, streptomycin, metalaxyl, furalaxyl, benalaxyl, furalamide, carbendazim, benomyl, thiophanate-methyl, triazolone, bupirimate the composition comprises pyriminostrobin, ethirimol, captan, folpet, ethephon, fluocinolone acetonide, dimethachlon, chlorothalonil, isoprothiolane, metrafil, pentrinitrobenzene, propineb, fosetyl-aluminum, sulfur, bordeaux, copper sulfate, cupric oxychloride, cuprous oxide, cupric hydroxide, metrafenone, pencycuron, pyridazinone, tetrachlorophthalide, fluquintone, spiroxamine, tricyclazole, zindolac, dodine, biguanidine, bispyrifos, chlornitramine, benzenesulfonamide, toschlorfenamide, indole esters, sodium, fluquintoxyl, probenazole, bronopol, iodomethane, valicarb, dixyl, dazomet, dichlorvos, fos, fenphos, triazophos, carbosulfan, sulfur, dichloropropene, dichlorisonicotinic acid, and probenazole; the total mass percentage of the pyrazole-containing dithiazole carboxamide derivative I in the bactericidal composition is 1% -90%, and the mass percentage of the pyrazole-containing dithiazole carboxamide derivative I and the commodity bactericide is 1% -99% -1%; the dosage form of the bactericidal composition is selected from the group consisting of: seed treatment emulsions, aqueous emulsions, microemulsions, suspoemulsions, capsule suspensions, water-soluble granules, fine granules, soluble concentrates, cereals, blocky baits, granular baits, sheeted baits, concentrated baits, slow release blocks, electrostatic sprays, oil-in-water emulsions, aerosol cans, aerosol candles, aerosol cans, aerosol sticks, aerosol flakes, aerosol pellets, aerosols, ointments, hot aerosols, cold aerosols, solid/liquid mixed packages, liquid/liquid mixed packages, solid/solid mixed packages, paint, microgranules, tracing powders, oil suspensions, oil dispersible powders, concentrated gels, sprinkles, seed coatings, spreads, film forming oils, ultra low volume liquids, vapor release agents; plant diseases for which the fungicidal composition is suitable are selected from: seedling blight, tomato root rot, potato late blight, tobacco black shank, millet powdery mildew, grape downy mildew, lettuce downy mildew, cucumber anthracnose; plants for which the fungicidal composition is suitable are selected from: rice, wheat, barley, oat, corn, sorghum, sweet potato, tapioca, soybean, netherlands, broad bean, pea, mung bean, cotton, mulberry, peanut, canola, sesame, sunflower, sugar beet, sugarcane, coffee, cocoa, ginseng, fritillaria, rubber, coconut, oil palm, sisal, tobacco, tomato, chilli, radish, cucumber, cabbage, celery, mustard, beet, rape, onion, garlic, watermelon, melon, cantaloupe, papaya, apple, citrus and peach, tea, wild herbs, bamboo shoots, hops, peppers, banana, papaya, orchid, bonsai.
Example 7: the application of the pyrazole-containing dithiazole carboxamide derivative I and the combination of the anti-plant virus agent in preventing and controlling viral diseases of agriculture and forestry and gardening plants:
the pyrazole-containing dithiazole carboxamide derivative I of the invention is combined with any one or two of commercial antiviral agents to form an antiviral composition for controlling viral diseases of agricultural, forestry and horticultural plants, wherein the commercial antiviral agents are selected from the group consisting of: benzothiadiazole, tiadinil, isotiadinil, ribavirin, antofine, ningnanmycin, mefenacet or salicylic acid, pyriminomycin, isonicotinic acid dichloride, allylisothiazole, validamycin, moroxydine hydrochloride; the total mass percentage of the pyrazole-containing dithiazole carboxamide derivative I in the antiviral composition is 1% -90%, and the mass percentage of the pyrazole-containing dithiazole carboxamide derivative I to the commercial plant virus resisting agent is 1% -99% -1%; the antiviral composition is formulated in 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, cereals, blocky baits, granular baits, sheeted baits, concentrated baits, slow release blocks, electrostatic sprays, oil-in-water emulsions, aerosol cans, aerosol candles, aerosol cans, aerosol sticks, aerosol flakes, aerosol pellets, aerosols, ointments, hot aerosols, cold aerosols, solid/liquid mixed packages, liquid/liquid mixed packages, solid/solid mixed packages, paint, microgranules, tracing powders, oil suspensions, oil dispersible powders, concentrated gels, sprinkles, seed coatings, spreads, film forming oils, ultra low volume liquids, vapor release agents; the virus diseases prevented and treated by the antiviral composition are selected from the following: rice dwarf, yellow dwarf, stripe disease, tomato fern leaf virus, pepper mosaic virus, tobacco vein necrosis virus, maize dwarf mosaic, cauliflower mosaic virus, citrus virus, cymbidium mosaic virus, cymbidium ringspot virus; the plants for which the antiviral composition is used for control are selected from: rice, wheat, barley, oat, corn, sorghum, sweet potato, tapioca, soybean, netherlands, broad bean, pea, mung bean, cotton, mulberry, peanut, canola, sesame, sunflower, sugar beet, sugarcane, coffee, cocoa, ginseng, fritillaria, rubber, coconut, oil palm, sisal, tobacco, tomato, chilli, radish, cucumber, cabbage, celery, mustard, beet, rape, onion, garlic, watermelon, melon, cantaloupe, papaya, apple, citrus and peach, tea, wild herbs, bamboo shoots, hops, peppers, banana, papaya, orchid, bonsai.
Example 8: the application of the combination of the pyrazole-containing dithiazole carboxamide derivative I and the acaricide in controlling mites of agricultural and forestry and horticultural plants:
the mite-killing composition formed by combining any one or two of pyrazole-thiazole carboxamide derivatives I and commercial acaricides is used for preventing and controlling mites of agricultural, forestry and horticultural plants, and the commercial acaricides are selected from the following: dichlorvos, heptylphosphines, fast-acting phoxims, dibromophoxims, pyrimidophos, chlormethiphos, ethion, chlorfenphos, valphos, methyl pyrimidothioate, quetiaphos, triazamate, chlorpyrifos, fenphos, flumethrin, bifenthrin, cyhalothrin, lambda-cyhalothrin, fenpropathrin, flumethrin, cyfluthrin, bromfluthrin, bifenazate, benfuracarb, butanone, carbofuran, mefenoxam, benomyl, chlormefos, ding Liusu carbofuran acarb, benzyl benzoate, bromopropylate, cyflumetofen, chloranil, flumetofen, flufenoxuron, liuyangmycin, chongmycin, thuringiensis, acaricide, liuyangmycin, avermectin, doramectin, eprinomectin, ivermectin, siramectin, moxidectin, pyrethrin, nicotine, matrine, azadirachtin, rotenone, tebufenpyrad, pyridaben, fenpyroximate, clofentezine, propargite, hexythiazox, spirodiclofen, azoxystrobin, acaricide, clofentezine; the total mass percentage of the pyrazole-containing dithiazole carboxamide derivative I in the acaricidal composition is 1% -90%, and the mass percentage of the pyrazole-containing dithiazole carboxamide derivative I to the commercial acaricide is 1% -99% -1%; the formulation of the acaricidal composition is selected from the group consisting of: seed treatment emulsions, aqueous emulsions, microemulsions, suspoemulsions, capsule suspensions, water-soluble granules, fine granules, soluble concentrates, cereals, blocky baits, granular baits, sheeted baits, concentrated baits, slow release blocks, electrostatic sprays, oil-in-water emulsions, aerosol cans, aerosol candles, aerosol cans, aerosol sticks, aerosol flakes, aerosol pellets, aerosols, ointments, hot aerosols, cold aerosols, solid/liquid mixed packages, liquid/liquid mixed packages, solid/solid mixed packages, paint, microgranules, tracing powders, oil suspensions, oil dispersible powders, concentrated gels, sprinkles, seed coatings, spreads, film forming oils, ultra low volume liquids, vapor release agents; the mite injury prevented and controlled by the mite-killing composition is selected from the following components: the mites are selected from the group consisting of Tetranychidae, phyllophaceae, fusarium, goiter, tetranychus, and goiter, and are world agricultural, forestry, horticultural, and hygiene mites; the plants for which the acaricidal composition is used for control are selected from the group consisting of: rice, wheat, barley, oat, corn, sorghum, sweet potato, tapioca, soybean, netherlands, broad bean, pea, mung bean, cotton, mulberry, peanut, canola, sesame, sunflower, sugar beet, sugarcane, coffee, cocoa, ginseng, fritillaria, rubber, coconut, oil palm, sisal, tobacco, tomato, chilli, radish, cucumber, cabbage, celery, mustard, beet, rape, onion, garlic, watermelon, melon, cantaloupe, papaya, apple, citrus and peach, tea, wild herbs, bamboo shoots, hops, peppers, banana, papaya, orchid, bonsai.
Industrial applicability
The invention provides pyrazole-containing dithiazole carboxamide derivatives. The derivative can regulate and control the biological activity of plant pests and plant pathogens in agriculture, gardening and sanitation and forestry, can be used for killing insects, mites, bacteria and plant viruses in the agricultural field, the gardening field and the forestry field, induces plants to generate disease resistance, and has good economic value and application prospect.
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TABLE 2 bacteriostatic Activity of the pyrazole-containing dithiazole carboxamide derivative I of the present invention (inhibition rate of 50. Mu.g/ml/%)
Sequence number Numbering of compounds A.s B.c C.a F.g F.v P.p R.c R.s S.s
1 I-1 15 63 31 47 25 22 26 53 21
2 I-2 25 66 41 45 30 32 33 53 26
3 I-3 0 21 17 33 24 16 29 21 8
4 I-4 15 81 21 58 35 35 50 60 19
5 I-5 35 79 35 40 45 47 59 60 26
6 I-6 0 44 17 54 15 6 25 33 7
7 I-7 11 58 24 47 30 32 38 58 26
8 I-8 9 59 10 73 11 10 15 8 0
9 I-9 11 100 31 66 24 21 80 56 14
10 I-10 19 59 21 66 15 20 17 34 0.
11 I-11 11 37 29 44 8 12 17 47 0
12 I-12 0 60 29 64 10 0 0 34 0
13 Thifluzamide 65 59 82 35 22 39 56 85 88
A.s: the Latin name of the early blight bacteria of tomato is: alternaria solani, b.c: the Latin name of the Botrytis cinerea is: botrytis cinerea, C.a: peanut brown spot germ, its latin name is: cercospora arachidicola, F.g: fusarium graminearum, its Latin name is: fusarium graminearum, F.v: fusarium verticillium, the Latin name of which is: fusarium verticillioides, P.p: apple ring rot germ, its latin name is: physalospora piricola, R.c: rhizoctonia cerealis, its Latin name is: rhizoctonia cerealis, R.s: rhizoctonia solani, its Latin name is: rhizoctonia solani, S.s: sclerotinia sclerotiorum, the Latin name of which is: sclerotinia sclerotiorum.

Claims (7)

1. A pyrazole-containing dithiazole carboxamide derivative is characterized in that the structure of pyrazole and thiazole simultaneously has a structural general formula shown in a formula I:
wherein R is selected from: 1-isopropoxy-3-phenyl, 3-phenoxy-1-phenyl, 1,2,3, 4-tetrahydronaphthalen-5-yl, 2, 3-indan-4-yl, 1-naphthyl, 1- (tert-butyl) -3-phenyl, 2-bromo-3-methyl-1-phenyl, m-isopropylphenyl, 1' -biphenyl-3-yl, 4' -chloro-1, 1' -biphenyl-2-yl, benzo [ d ] [1,3] diazol-4-yl, 1, 3-dibromo-5- (trifluoromethoxy) benzene-2-yl, 1, 3-dichloro-5- (trifluoromethoxy) benzene-2-yl, 1,3, 5-trichlorobenzene-2-yl, 1-bromo-3-methoxybenzene-5-yl, 2-bromo-1- (trifluoromethoxy) benzene-4-yl, 1-bromo-2- (trifluoromethyl) benzene-4-yl, 1-bromo-3-methoxybenzene-5-yl, 2-bromo-1-4-methoxy-2-methyl-4-yl, trifluoromethyl-2-bromo-4-phenyl.
2. The specific synthetic route and method of the N-heterocyclic aromatic hydrazone derivative I according to claim 1 are as follows:
the definition of the substituent is as in claim 1, and the specific synthesis method comprises the following steps:
A. preparation of compound 2:
adding oxalyl chloride and N, N-dimethylformamide into the compound 1 and dichloromethane, after stirring reaction at room temperature, concentrating under reduced pressure, evaporating solvent, and diluting with dichloromethane; dropwise adding the dichloromethane solution of the residue into the 25% ammonia water solution of the single-neck round-bottom flask by using a constant-pressure dropping funnel under the ice bath condition, stirring overnight, and carrying out vacuum suction filtration to obtain a compound 2;
B. Preparation of compound 3:
adding 2 and Lawson reagents into a reaction bottle, dissolving in tetrahydrofuran solution, heating and refluxing, spotting a plate to judge that the reaction is finished, carrying out vacuum filtration, concentrating filtrate, and removing a solvent; dissolving and diluting with ethyl acetate, washing with saturated potassium carbonate solution, separating out water layer, and extracting with ethyl acetate; the combined organic layers were washed with saturated sodium chloride solution and dried over anhydrous sodium sulfate; vacuum filtering, concentrating the filtrate to remove solvent; purifying by petroleum ether/ethyl acetate eluent column chromatography to obtain compound 3;
C. preparation of Compound 4:
adding 3 into a reaction bottle, dissolving in ethanol, and dropwise adding ethyl bromopyruvate by using a syringe; heating and refluxing the mixed solution, carrying out reduced pressure suction filtration after the point plate monitoring reaction is finished, and concentrating filtrate to remove solvent; dissolving and diluting with ethyl acetate, washing with saturated sodium bicarbonate solution, separating out water layer, and extracting with ethyl acetate; the combined organic layers were washed with saturated sodium chloride solution and dried over anhydrous sodium sulfate; vacuum filtering, concentrating the filtrate to remove solvent, and purifying by petroleum ether/ethyl acetate eluent column chromatography to obtain compound 4;
D. preparation of compound 5:
adding 4 into a mixed solution of sodium hydroxide solution and ethanol in a single-neck round bottom flask, and gradually heating and refluxing; after the reaction is completed, pouring the reaction solution into a beaker, adjusting the pH of the solution by hydrochloric acid, and filtering to obtain a compound 5;
E. Preparation of Compound I:
adding 5, N-diisopropylethylamine into a reaction flask, dissolving in dichloromethane, and stirring at room temperature; after the solid is dissolved, adding benzotriazol-1-yl-oxy-tripyrrolidinyl phosphate hexafluorophosphate under ice bath condition, adding corresponding amine, stirring overnight at room temperature, washing with water after the reaction is finished, separating out an aqueous layer, extracting with dichloromethane, washing a combined organic layer with saturated sodium chloride solution, and drying with anhydrous sodium sulfate; vacuum filtering, concentrating the filtrate to remove solvent, and purifying with petroleum ether/ethyl acetate eluent column chromatography to obtain the corresponding product.
3. Use of a pyrazole-containing dithiazole carboxamide derivative I as described in claim 1 for the preparation of an agricultural fungicide.
4. An agricultural fungicidal composition comprising the pyrazole-containing dithiazole carboxamide derivative I as defined in claim 1 and an intermediate, which can be prepared as an agricultural fungicidal composition comprising the pyrazole-containing dithiazole carboxamide derivative I as defined 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 comprises the pyrazole-contained dithiazole formamide derivative I and other commercial bactericides as active ingredients, wherein the mass percentage of the pyrazole-contained dithiazole formamide derivative I to the other commercial bactericides is 1 to 99 to 1 percent, and the content of the active ingredients is 1 to 99 percent by weight and 99 to 1 percent by weight of solid or liquid auxiliary agent.
6. An agricultural insecticidal and acaricidal compound composition comprises the pyrazole-contained dithiazole carboxamide derivative I and other commercial pesticides and acaricides as active ingredients, wherein the mass percentage of the pyrazole-contained dithiazole carboxamide derivative I to other commercial pesticides and acaricides is 1% -99% -1%, the content of the active ingredients is 1% -99% by weight, and the content of the active ingredients is 99% -1% by weight of solid or liquid auxiliary agents.
7. An anti-plant virus agent compound composition comprising the pyrazole-containing dithiazole carboxamide derivative I according to claim 1 and other commercial anti-plant virus agents as active ingredients, wherein the ratio of the pyrazole-containing dithiazole carboxamide derivative I to the other commercial anti-plant virus agents is 1% to 99% to 1% by mass, and the content of the active ingredients is 1 to 99% by weight, and 99 to 1% by weight of a solid or liquid auxiliary agent.
CN202310905524.4A 2023-07-24 2023-07-24 Pyrazole-containing dithiazole carboxamide derivative and preparation method and application thereof Pending CN116891466A (en)

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