CN112480103A - Coumarin derivatives containing 3, 4-dichloroisothiazole and preparation method and application thereof - Google Patents
Coumarin derivatives containing 3, 4-dichloroisothiazole and preparation method and application thereof Download PDFInfo
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- 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
- A01N43/80—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 1,2
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Abstract
The invention provides coumarin derivatives containing 3, 4-dichloroisothiazole, a preparation method and application thereof, and particularly relates to coumarin compounds containing 3, 4-dichloroisothiazole, wherein the chemical structural general formula of the coumarin compounds is shown as formula I: i:
Description
Technical Field
The technical scheme of the invention relates to a coumarin compound containing 3, 4-dichloroisothiazole, in particular to a coumarin compound of 3, 4-dichloroisothiazole, namely a 7-or 5-hydroxy coumarin derivative of a 4-bit 3, 4-dichloroisothiazole heterocycle.
Background
The heterocyclic compound has high-efficiency, low-toxicity and broad-spectrum biological activity, and most of the biological active compounds reported in patent documents have heterocyclic structures; the literature reports that the five-membered heterocyclic compound has the activities of a plant activator, a bactericide, a plant growth regulator and an insecticide (Chendanping, modern pesticide, 2014, 14 (2): 5-10), wherein the coumarin compound has the physiological activities of cancer resistance, antibiosis, anti-inflammation, antioxidation and the like, and also has good agricultural activities of insecticide, sterilization and the like. Recent researches show that the coumarin compound has more outstanding acaricidal activity and unique action targets, and has the potential of developing novel acaricides (Liu loop forest, etc.. the agricultural and pharmaceutical science, 2019, 21 (5-6): 692-.
The agricultural bactericide plays an irreplaceable role in ensuring the grain safety, at present, the agricultural bactericide has a plurality of varieties, but has few action targets, and the varieties with the same action mechanism are easy to generate drug resistance and cross resistance after being applied, so that the development of more high-efficiency low-toxicity environment-compatible new bactericides is the demand of pesticide decrement application strategy and high-toxicity pesticide variety replacement; in order to search for a new guide and a new action target of the bactericide, the invention aims at the foundation of the excavation of the new action target, carries out guide optimization and the research of the action target thereof based on the guide structure of an active natural product and by combining the means of creating reasonable molecular design of a new pesticide so as to obtain a new high-activity compound or a new action target, and contributes to the enrichment of the variety and the action target of the bactericide and the overcoming of drug resistance.
In order to find and discover pesticide lead and candidate compounds which are more efficient, broad-spectrum, low-toxicity, low-ecological-risk and free of cross resistance, the invention introduces 3, 4-dichloroisothiazole heterocycle into the lead structure of coumarin, designs and synthesizes 4-position 3, 4-dichloroisothiazole heterocycle 7-position or 5-position hydroxycoumarin 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 4-position 3, 4-dichloroisothiazole heterocyclic 7-position or 5-position hydroxycoumarin derivatives, provides a method for regulating and controlling the biological activity of agricultural, horticultural and sanitary pests and plant pathogens of forestry plants and a determination method thereof by using the compounds, and simultaneously provides application 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 coumarin derivative containing 3, 4-dichloroisothiazole, which has insecticidal, acaricidal, bactericidal and plant virus resistant activities and can induce plants to generate disease resistant activities in the fields of agriculture, horticulture and forestry, is shown as I:
I：
wherein R is1Selected from: hydrogen, methyl, chlorine. R2Selected from: hydrogen, methyl, ethyl, fluorine, chlorine.
The synthetic route of the coumarin derivative I containing 3, 4-dichloroisothiazole and the intermediate thereof is as follows:
the synthesis method of the coumarin derivative I containing 3, 4-dichloroisothiazole comprises the following steps:
synthesizing a coumarin derivative I containing 3, 4-dichloroisothiazole:
3, 4-dichloroisothiazole-beta-keto ester 1(1.0 mmol) and substituted resorcinol 2(1.1 mmol) were dispersed in dry trifluoroacetic acid (2.0 ml) and the solution was stirred at room temperature. Heating and refluxing for 2-12 hours. After the reaction was completed by thin layer chromatography, the reaction mixture was concentrated, ethyl acetate (10 ml) and water (10 ml) were added, the mixture was stirred and left to stand for separation, the aqueous phase was extracted with ethyl acetate (2 × 10 ml), the organic phases were combined, the organic phase was washed successively with saturated sodium bicarbonate solution, water and saturated brine, and dried by adding anhydrous sodium sulfate. Vacuum filtering, concentrating, and performing column chromatography (V)Petroleum ether∶VEthyl acetateAnd (2) purifying the obtained product at a ratio of 10: 1-3: 1) to obtain the coumarin derivative I containing 3, 4-dichloroisothiazole. The preparation amount of the compound I and the volume of a reaction vessel are enlarged or reduced according to corresponding proportion;
wherein, the substituent R1、R2As defined above; r1Selected from: hydrogen, methyl, chlorine. R2Selected from: hydrogen, methyl, ethyl, fluorine, chlorine.
The invention provides application of the coumarin derivative I containing 3, 4-dichloroisothiazole in preparation of fungicides.
The invention provides application of the coumarin derivative I containing 3, 4-dichloroisothiazole in preparation of a tobacco mosaic virus resistant agent.
The invention provides application of the coumarin derivative I containing 3, 4-dichloroisothiazole in preparation of a plant activator for inducing tobacco to resist tobacco mosaic virus.
The invention provides application of the coumarin derivative I containing 3, 4-dichloroisothiazole in prevention and treatment of agricultural and forestry and horticultural plant insect pests.
The coumarin derivative I containing the 3, 4-dichloroisothiazole is applied together with agricultural chemicals; the agrochemical is selected from: one or more of insecticide, bactericide, plant virus resisting agent and acaricide.
The coumarin derivative I containing the 3, 4-dichloroisothiazole and any one or two of the insecticides are combined to form an insecticidal composition for preventing and treating insect pests of agricultural and forestry and horticultural plants;
the insecticide is selected from: methoprene, diazinon, acetamiprid, emamectin benzoate, milbemectin, abamectin, pleocidin, metaflumethrin, cyhalothrin, lambda-cypermethrin, lambda-cyhalothrin, permethrin, allethrin, bifenthrin, permethrin, flumethrin, cyhalothrin, imidacloprid, nitenpyram, imidacloprid, thiacloprid, thiamethoxam, clothianidin, dinotefuran, flufenoxuron, lufenuron, chlorfluazuron, fluazuron, diflubenzuron, fluazuron, teuron, novaluron, flufenoxuron, fluazuron, flufenoxuron, fluazuron, tezine, flufenozide, teflufenozide, tebufenozide, tezine, flufenozide, tebufenozide, flufenozide, flufeno, Chlorantraniliprole, methoxyfenozide, chromafenozide, dichlorvos, quinalphos, pyridaphenthion, cicada powder, carbaryl, pirimicarb, metolcarb, isoprocarb, cartap, fenobucarb, tetrafenozide, fenitrothion, chlorfenpyr, tetrafenozide, fenitrothion, hexythiazox, fenpyroximate, pyridaben, clofentezine, diafenthiuron, pymetrozine, spirodiclofen, spirotetramat, azocyclotin, buprofezin, monosultap, dimehypo, chlorantraniliprole, tetrachlorantranilide, flubendiamide, cyantraniliprole, crotafloxacin, tolfenpyrazamide, chlorfenapyr, imazemazone, imazalil, tebufenpyrad, pyridalyl, pyriproxyfen, emamectin, and guadipyridamole;
the mass percentage of the coumarin derivative I containing 3, 4-dichloroisothiazole in the insecticidal composition is 1% -90%; preferably, the ratio of the 3, 4-dichloroisothiazole-containing coumarin derivative I to the pesticide is 1 to 99 to 1 percent in percentage by mass;
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 controlled by the insecticidal composition are selected from: meadow spodoptera, red spider, east Asian migratory locust, spruce-bug, Chinese rice locust, japanese yellow-back locust, mole cricket alone, mole cricket orientalis, rice thrips, thrips tabaci, green house thrips, rice thrips, simply tubular thrips, green house whitefly, black tail hopper, big leafhopper, cotton leafhopper, lesser leafhopper, brown plant hopper, white back plant hopper, gray plant hopper, sugarcane planthopper, cotton aphid, binary wheat aphid, green peach aphid, sorghum aphid, radish aphid, mealybug, lybug, stinkbug, arrowhead, round scale, white insect, red wax insect, red insect, mealybug, pear net, banana net bug, small horned bug, tiny laceleaf fly, green fly, rice moth, black armyworm, black rice moth, black rice green fly, black rice plant, black rice, 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 controlled by the insecticidal composition are 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 coumarin derivative I containing the 3, 4-dichloroisothiazole 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, thifluzamide, DL-beta-aminobutyric acid, isotianil, ribavirin, antofine, ningnanmycin or salicylic acid, cymoxanil, thiram, mancozeb, fosetyl-aluminium, thiophanate-methyl, chlorothalonil, dichlorvos, procymidone, fenpropidin, thiophanate-methyl, metalaxyl-M, flumorphine, dimethomorph, propamocarb, dichlormid, flusulfamide, sulfenamide, thifluvalicarb-isopropyl, cyprodinil, cyhalodiamide, silthiopham, carboxin, metalaxyl oxide, furamex, triflumimide, furametryn, thifluzamide, boscalid, penthiopyrad, pyrazopyram, bixafen, fluopyram, fluoxafen, epoxiconazole, fenpyraclostrobin, flutriafolan, flufenazamide, flufenapyr-methyl, flufenamate, flufenapyr, thiflufenamate, flufenamate, flufenapyr, thiflufenamate, benconazole, iprazole, flufenacet, fluxapyroxad, flufenacet, flufenamid, mandipropamid, fenhexamid, ethiprole, iprodione, azoxystrobin, dimoxystrobin, fluoxastrobin, kresoxim-methyl, metominostrobin, picoxystrobin, trifloxystrobin, enestroburin, alkene oxime amine, epoxiconazole, bromuconazole, cyproconazole, difenoconazole, diniconazole, tebuconazole, fenbuconazole, fluquinconazole, flusilazole, flutriafol, hexaconazole, ipconazole, metconazole, myclobutanil, penconazole, propiconazole, prothioconazole, simeconazole, tebuconazole, tetraconazole, triadimenol, triticonazole, bitertanol, thiabendazole, imazalil, prochloraz, cyazofamid, pyraclostrobin, fenamidone, famoxadone, isoprothiolane, imazalil, Pyrisoxazole, hymexazol, oxadixyl, ethaboxam, hymexazol, octreone, thiobencarb, dodemorph, fenpropimorph, tridemorph, fenpiclonil, fludioxonil, fluazinam, pyrifenox, cyprodinil, fluopicolide, pyrimethanil, cyprodinil, mepanipyrim, pyrimethanil, fenamidol, fluoropyrimidinol, flufenamidol, fenamiphen, dithianon, ethoxyquinoline, hydroxyquinoline, propoxymine, phenoxyquinoline, diethofencarb, iprovalicarb, benthiavalicarb, propamocarb, edifenphos, iprobenfos, pyrazophos, tolon, tolfenclofos, kasugamycin, polyoxin, validamycin, jinggangmycin, streptomycin, metalaxyl, furalaxyl, benalaxyl, furalaxyl, carbendazim, benomyl, thiophanaton, thizalone, triadimefon, fenamidone, fenamidothiobac, pyrimethanil, Ethirimol, captafol, captan, folpet, vinclozolin, fluoxynil, dimethachlon, chlorothalonil, isoprothiolane, metconazole, quintozene, propineb, fosetyl-aluminum, sulfur, bordeaux, copper sulfate, copper oxychloride, cuprous oxide, copper hydroxide, metrafenone, pencycuron, pyridaben, tetrachlorophthalide, pyroquilon, spiroxamine, tricyclazole, fluazinam, dodine, iminoctadine, octylamine, clonidine, benthiamid, indoxyl, diuron, quinconazole, probenazole, bronopol, methyl iodide, metam, fenamate, dazomet, dichloroprofen, fosthiazate, foscarnet, fenamiphos, dichlofos, thiocarb, thioflonicamid, dichloropropylene, dichlorisoisothiazole;
the total mass percentage of the 3, 4-dichloroisothiazole-containing coumarin derivative I in the bactericidal composition is 1% -90%; the ratio of the 3, 4-dichloroisothiazole-containing coumarin derivative I to the bactericide is 1 to 99 to 1 percent by mass 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 controlled by the bactericidal composition are selected from: 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 coumarin derivative I containing the 3, 4-dichloroisothiazole and any one or two of the antiviral medicaments 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 DL-beta-aminobutyric acid, 2, 6-dichloroisonicotinic acid, N-cyanomethyl-2-chloroisonicotinamide, allylisothiazole, ribavirin, antofine, ningnanmycin, methicillin-induced amine or salicylic acid, pyriminomycin, dichloroisonicotinic acid, allylisothiazole, validamycin, moroxydine hydrochloride;
the total mass percentage of the coumarin derivative I containing the 3, 4-dichloroisothiazole in the antiviral composition is 1-90%; preferably, the ratio of the 3, 4-dichloroisothiazole-containing coumarin 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 plants for preventing and treating the antiviral composition are 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 coumarin derivative I containing the 3, 4-dichloroisothiazole and any one or two of the acaricides are combined to form an acaricide composition for preventing and controlling acarid pests of agricultural, forestry and horticultural plants;
the acaricide is selected from: dichlorvos, heptenophos, metophos, dibromophos, pirimiphos-methyl, ethion, chlorfenvinphos, vofenphos, pirimiphos-methyl, quinalphos, aphidmethomyl, amicarbaz, chlorfenphos, phosmet, fluthrin, bifenthrin, cyhalothrin, lambda-cyhalothrin, fenpropathrin, bifenazate, fenobucarb, butoxycarb, oxamyl, carbofuran, monocarb, benomyl, cloxacarb, butathion, lufenuron, benzoate, bromopropylate, cyflumetofen, flufenpyr, flufenoxuron, chlorfenapyr, sumicin, miticide, ruscin, avermectin, doramectin, norubicin, eprinomectin, ivermectin, larmectin, moxidectin, chrysanthemin, nicotine, alkali, dimethomorphin, chlorfenapyr, Nimbin, rotenone, tebufenpyrad, pyridaben, fenpyroximate, clofentezine, propargite, hexythiazox, spirodiclofen, fluacrypyrim, acaricide, propargite and pyridaben;
the total mass percentage of the coumarin derivative I containing the 3, 4-dichloroisothiazole in the acaricidal composition is 1% -90%; the ratio of the 3, 4-dichloroisothiazole-containing coumarin derivative I to the acaricide is 1 to 99 to 1 percent by mass percent;
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 controlling 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 coumarin derivative I containing 3, 4-dichloroisothiazole is determined as follows:
the bactericidal activity of the coumarin derivative I containing 3, 4-dichloroisothiazole is determined as follows:
the bactericidal or bacteriostatic activity of the coumarin derivative I containing 3, 4-dichloroisothiazole is measured by a thallus growth rate measuring method, and the method comprises the following specific steps: dissolving 1.8 mg of sample in 2 drops of dimethyl sulfoxide, diluting the sample to 500 micrograms/ml of medicament with aqueous solution containing a certain amount of Tween 20 emulsifier, sucking 1 ml of the reagent to be tested in a culture dish under an aseptic condition, adding 9 ml of PDA culture medium respectively, shaking uniformly to prepare a 50 micrograms/ml medicament-containing flat plate, 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 to be placed in an equilateral triangle, repeating the treatment for 3 times, placing the culture dish in a constant-temperature culture box at 24 +/-1 ℃ for culturing, 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 average value, comparing with the blank control to calculate the relative bacteriostasis rate, wherein the test bacterial strain is the species of most of typical plant pathogenic bacteria actually generated in the field in agricultural production in 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 coumarin derivative I containing 3, 4-dichloroisothiazole is subjected to lead optimization, and the coumarin derivative I containing 3, 4-dichloroisothiazole is subjected to antibacterial activity screening.
The synthesis, biological activity and application of coumarin derivatives I containing 3, 4-dichloroisothiazole 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 implementation modes are as follows:
example 1: preparation of Compound I-1:
3, 4-Dichloroisothiazole- β -keto ester 1-2a (268 mg, 1.0 mmol) and resorcinol (121 mg, 1.1 mmol) were dispersed in dry trifluoroacetic acid (2.0 ml) and the solution was stirred at room temperature. The reaction was heated under reflux for 12 hours. After the reaction was completed by thin layer chromatography, the reaction mixture was concentrated, ethyl acetate (10 ml) and water (10 ml) were added, the mixture was stirred and left to stand for separation, the aqueous phase was extracted with ethyl acetate (2 × 10 ml), the organic phases were combined, the organic phase was washed successively with saturated sodium bicarbonate solution, water and saturated brine, and dried by adding anhydrous sodium sulfate. Vacuum filtering, concentrating, and performing column chromatography (V)Petroleum ether∶VEthyl acetatePurifying the obtained product at a ratio of 10: 1-3: 1) to obtain a coumarin derivative I-1 containing 3, 4-dichloroisothiazole, wherein the yield is 85%; the nuclear magnetic data are as follows:1h NMR (400M Hz, DMSO-d6) δ 10.82(s, 1H), 7.22(d, J ═ 8.5Hz, 1H), 6.87-6.69(M, 2H), 6.41(s, 1H). The preparation amount of the compound I-1 and the volume of a reaction vessel are enlarged or reduced according to corresponding proportion;
the physicochemical and structural parameters of compound I are shown in Table 1.
Example 2: the determination result of the antibacterial activity of the coumarin derivative I containing 3, 4-dichloroisothiazole 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, with the latin name: 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. For the rhizoctonia cerealis, the inhibition rates of the compounds LY01-43, LY01-98, LY01-99, LY02-1, LY02-2, LY02-3, LY02-5, LY02-6, LY02-7, LY02-8, LY02-12, LY02-14, LY02-15, LY02-16, LY02-19, LY02-39, LY02-41 and LY02-47 reach over 90 percent, wherein the inhibition rates of the compounds LY01-43, LY01-98, LY01-99 and LY02-47 reach 100 percent and are respectively higher than that of the control drugs of azoxystrobin, pyraclostrobin, boscalid, isopyrazam 40 percent, 20 percent, 30 percent and 20 percent; for the verticillium pomorum, the inhibition rates of compounds LY01-43, LY01-98, LY01-99, LY02-1, LY02-2, LY02-3, LY02-5, LY02-7, LY02-12, LY02-14, LY02-15, LY02-39 and LY02-47 are all more than 90%, wherein the inhibition rate of the compound LY01-99 is up to 100%, which is respectively more than 30%, 10%, 30% and 10% higher than that of control drugs of azoxystrobin, pyraclostrobin, boscalid and isopyrazam; for sclerotinia sclerotiorum, the inhibition rates of compounds LY02-1, LY02-3, LY02-5, LY02-6, LY02-14, LY02-19, LY02-41 and LY02-47 are all more than 90 percent, and are equivalent to the control drugs of azoxystrobin, pyraclostrobin, boscalid and isopyrazam; the activity of the compound LY01-43, LY01-98, LY01-99, LY02-1, LY02-3, LY02-6, LY02-7, LY02-12, LY02-14, LY02-15, LY02-39, LY02-41 and LY02-47 shows that the inhibition rate is more than 80%, which is respectively higher than that of the control medicines azoxystrobin, boscalid and isopyrazam by more than 10%, 30% and 50%, and is equivalent to that of the control medicines pyraclostrobin, especially the inhibition rates of the compound LY01-99 and LY02-3 are the highest and reach 98%, and the antibacterial effect is better than that of the control medicines azoxystrobin, pyraclostrobin, boscalid and isopyrazam; for botrytis cinerea, the inhibition rates of compounds LY01-43, LY01-98, LY01-99, LY02-1, LY02-2, LY02-3, LY02-5, LY02-6, LY02-7, LY02-8, LY02-12, LY02-14, LY02-15, LY02-16, LY02-19, LY02-39, LY02-40, LY02-41 and LY02-47 are all more than 80%, better than that of the control drug azoxystrobin, equal to that of the control drug pyraclostrobin and slightly inferior to that of the control drugs boscalid and isopyrazam, wherein the inhibition rates of compounds LY02-1, LY02-3, LY02-5, LY02-6, LY02-7, LY02-12, 02-14, 02-15, LY02-41 and LY 3647-47 are higher than that of LY 02-47; for potato late blight bacteria, the inhibition rates of compounds LY01-43, LY01-99, LY02-1, LY02-2, LY02-3, LY02-7, LY02-8, LY02-12, LY02-15, LY02-16, LY02-39 and LY02-47 are all more than 80%, which are respectively more than 20%, 30% and 20% higher than those of control drugs azoxystrobin, pyraclostrobin, boscalid and isopyrazam, wherein the inhibition rate of the compound LY01-99 is the highest and reaches 92%; for peanut brown spot pathogen, the inhibition rate of compounds LY01-43, LY01-99, LY02-1, LY02-2, LY02-3, LY02-5, LY02-6, LY02-7, LY02-14, LY02-15, LY02-39, LY02-41 and LY02-47 reaches more than 80 percent, is 30 percent higher than that of the control drug azoxystrobin, is equivalent to the control drug pyraclostrobin, and is slightly inferior to the control drugs boscalid and isopyrazam; wherein the inhibition rates of compounds LY01-43, LY02-1, LY02-5, LY02-39, LY02-41 and LY02-47 are all above 90%; for the early blight of tomato, the inhibition rates of compounds LY01-43, LY01-98, LY01-99, LY02-1, LY02-2, LY02-3, LY02-6, LY02-7, LY02-8, LY02-12, LY02-14, LY02-16, LY02-19, LY02-39, LY02-41 and LY02-47 are all above 70 percent, are 30 percent higher than that of the control drug azoxystrobin and are equivalent to that of the control drugs boscalid and isopyrazam and are slightly inferior to that of the control drugs boscalid and isopyrazam; particularly, the inhibition rate of compound LY02-47 reaches 88%; the activity on rhizoctonia solani shows that the inhibition rate of compounds LY01-43, LY01-98, LY01-99, LY02-1, LY02-2, LY02-3, LY02-5, LY02-6, LY02-7, LY02-8, LY02-12, LY02-14, LY02-15, LY02-16, LY02-39, LY02-41 and LY02-47 reaches more than 70 percent, is respectively higher than that of control drugs boscalid and isopyrazam by more than 30 percent and 20 percent, is equivalent to that of the control drugs kresoxim-methyl and pyraclostrobin, and particularly reaches 89 percent of the inhibition rate of the compounds LY 01-43; in conclusion, compounds LY01-43, LY01-99, LY02-1, LY02-3, LY02-5, LY02-41, LY02-47 show broad-spectrum bactericidal activity.
Example 3: the application of the coumarin derivative I containing 3, 4-dichloroisothiazole in preparing the pesticide composition comprises the following steps:
the invention relates to a pesticide composition prepared from 3, 4-dichloroisothiazole-containing coumarin derivatives I, which comprises the 3, 4-dichloroisothiazole-containing coumarin derivatives I and intermediates thereof as active ingredients, wherein the active ingredients comprise 0.1-99.9% by weight of solid or liquid auxiliaries 99.9-0.1% by weight of solid or liquid auxiliaries and optionally 0-50% by weight of surfactant.
Example 4: the application of the coumarin derivative I containing 3, 4-dichloroisothiazole in preparing the pesticide compound composition comprises the following steps:
the coumarin derivative I containing 3, 4-dichloroisothiazole and the intermediate thereof can be compounded with other commercial pesticides, namely insecticides, acaricides, bactericides, antiviral agents or plant activators to prepare a pesticide compound composition, the compound composition comprises the coumarin derivative I containing 3, 4-dichloroisothiazole and the intermediate thereof and other commercial pesticides, namely insecticides, acaricides, bactericides, antiviral agents or plant activators, as active ingredients, the coumarin derivative I containing 3, 4-dichloroisothiazole and the intermediate thereof and other commercial pesticides, namely insecticides, acaricides, bactericides, antiviral agents or plant activators, are mixed according to the mass percentage of 1 percent to 99 percent to 1 percent, the content of the active ingredients is 0.1 to 99.9 percent by weight, and the solid or liquid auxiliary agent is 99.9 to 0.1 percent by weight, and optionally from 0 to 50% by weight of a surfactant.
Example 5: the application of the combination of the coumarin derivative I containing the 3, 4-dichloroisothiazole and the pesticide in preventing and treating the insect pests of agricultural, forestry and horticultural plants is as follows:
the 3, 4-dichloroisothiazole-containing coumarin derivative I and one or two of commercial insecticides are combined to form a pesticidal composition for controlling agricultural and forestry and horticultural plant pests, wherein the commercial insecticide is selected from the following components: methoprene, diazinon, acetamiprid, emamectin benzoate, milbemectin, abamectin, pleocidin, metaflumethrin, cyhalothrin, lambda-cypermethrin, lambda-cyhalothrin, permethrin, allethrin, bifenthrin, permethrin, flumethrin, cyhalothrin, imidacloprid, nitenpyram, imidacloprid, thiacloprid, thiamethoxam, clothianidin, dinotefuran, flufenoxuron, lufenuron, chlorfluazuron, fluazuron, diflubenzuron, fluazuron, teuron, novaluron, flufenoxuron, fluazuron, flufenoxuron, fluazuron, tezine, flufenozide, teflufenozide, tebufenozide, tezine, flufenozide, tebufenozide, flufenozide, flufeno, Chlorantraniliprole, methoxyfenozide, chromafenozide, dichlorvos, quinalphos, pyridaphenthion, cicada powder, carbaryl, pirimicarb, metolcarb, isoprocarb, cartap, fenobucarb, tetrafenozide, fenitrothion, chlorfenpyr, tetrafenozide, fenitrothion, hexythiazox, fenpyroximate, pyridaben, clofentezine, diafenthiuron, pymetrozine, spirodiclofen, spirotetramat, azocyclotin, buprofezin, monosultap, dimehypo, chlorantraniliprole, tetrachlorantranilide, flubendiamide, cyantraniliprole, crotafloxacin, tolfenpyrazamide, chlorfenapyr, imazemazone, imazalil, tebufenpyrad, pyridalyl, pyriproxyfen, emamectin, and guadipyridamole; the mass percentage of the 3, 4-dichloroisothiazole-containing coumarin derivative I in the insecticidal composition is 1% -90%, and the mass percentage of the 3, 4-dichloroisothiazole-containing coumarin 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 controlled 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 controlled by the insecticidal composition are 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 6: the application of the combination of the coumarin derivative I containing the 3, 4-dichloroisothiazole and the bactericide in preventing and treating agricultural, forestry and horticultural plant diseases comprises the following steps:
the 3, 4-dichloroisothiazole-containing coumarin derivative I and one or two of commercial bactericides are combined to form a bactericidal composition for preventing and treating agricultural, forestry and horticultural plant diseases, wherein the commercial bactericides are selected from the following components: benzothiadiazole, tiadinil, 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, cymoxanil, thiram, mancozeb, fosetyl-aluminium, thiophanate-methyl, chlorothalonil, dichlorson, procymidone, fenpropidin, thiophanate-methyl, Thiophanate, metalaxyl-M, flumorph, dimethomorph, metalaxyl-M, benalaxyl-M, diclorocyanid, sulfenamide, thifluzamide, folpet, cyprodinil, cyflufenamid, fenhexamid, silthiopham, carboxin, oxicarb, mepiquat-chloride, fenazamide, flutolanil, furametpyr, thifluzamide, boscalid, penthiopyrad, isopyrazamide, bixafen, fluopyram, flufenamide, flufenapyr, fenpyrad, iprodione, fenpyrad, flufen-ethyl, trifloxystrobin, metominostrobin, trifloxystrobin, trifloxys, Dimethomorph, epoxiconazole, bromuconazole, cyproconazole, difenoconazole, diniconazole, tebuconazole, epoxiconazole, fenbuconazole, fluquinconazole, flusilazole, flutriafol, hexaconazole, imibenconazole, ipconazole, metconazole, myclobutanil, penconazole, propiconazole, prothioconazole, simeconazole, tebuconazole, tetraconazole, triadimenol, triticonazole, bitertanol, thiabendazole, fuberidazole, imazalil, prochloraz, triflumizole, cyazofamid, fenamidone, oxfendazole, pyrazofen, pyrazofenoxate, difenoconazole, oxadixyl, metoclopramide, hymexazol, octhiolone, benthiazoline, dodecorph, fenpropimorph, tridemorph, fenpyroxafen, fluazinam, boscalid, fenbutamol, fenpyrazamide, fenpyraclostrobin, fluazinam, fenthizamide, fenpyraclostrobin, fluzamine, fenbutamol, fenpyraclostrobin, fluzamine, flutriafolan, flutriafolpet, fluazinam, Pyrimethanil, fenarimol, flufenarimol, mefenamate, dithianon, ethoxyquin, hydroxyquinoline, propoxymine, phenoxyquinoline, diethofencarb, iprovalicarb, benthiavalicarb, propamocarb, sulbencarb, edifenphos, iprobenfos, pyraoxystrobin, tolclofos-methyl, blasticidin, kasugamycin, polyoxin, validamycin, streptomycin, metalaxyl, furalaxyl, benomyl, thiophanate-methyl, triadimefon, bupirimate, dimethirimol, ethirimol, captan, folpet, ethephrilil, flucloxacillin, dimethachlon, chlorothalonil, isoprothiolane, pefurazone, metconazole, quintozene, propineb, fosetyl, sulfur, polidol, cuprous oxide, cupric hydroxide, metrafenone, copper oxide, metrafenone, copper oxide, benezide, isoprothiolane, piridol, carbenicillin, carbenicin, polyoxin, chlorfenapyr, Pencycuron, pyridaben, tetrachlorophthalide, pyroquilon, spiroxamine, tricyclazole, azinam, dodine, diguanidinium salt, diguanidinium amine, niclosamide, benthiamid, tolfenbutamid, indoleester, sodium diuron, quinacrone, probenazole, bronopol, methyl iodide, metam, dichlofenamate, dazomet, dichloroisopropyl ether, fosthiazate, fosfon, fenamiphos, dichlofenthion, dichlorisonic acid, probenazole; the total mass percentage of the coumarin derivative I containing 3, 4-dichloroisothiazole in the bactericidal composition is 1% -90%, and the mass percentage of the coumarin derivative I containing 3, 4-dichloroisothiazole and the commercial bactericide is 1% -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 controlled by the bactericidal composition are selected from: 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 combination of the coumarin derivative I containing 3, 4-dichloroisothiazole and the plant virus resisting agent in preventing and treating virus diseases of agricultural, forestry and horticultural plants is as follows:
the coumarin derivative I containing 3, 4-dichloroisothiazole 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: diazosulfide, tiadinil, isotianil, DL-beta-aminobutyric acid, ribavirin, antofine, ningnanmycin, methicillin or salicylic acid, pyriminomycin, dichloroisonicotinic acid, probenazole, validamycin, moroxydine hydrochloride; the total mass percentage of the coumarin derivative I containing 3, 4-dichloroisothiazole in the antiviral composition is 1% -90%, and the ratio of the coumarin derivative I containing 3, 4-dichloroisothiazole to the commercial anti-plant virus agent is 1% to 99% to 1% 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 plants for preventing and treating the antiviral composition are 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 combination of the coumarin derivative I containing the 3, 4-dichloroisothiazole and the acaricide in preventing and treating the mite damage of agricultural, forestry and horticultural plants is as follows:
the coumarin derivative I containing 3, 4-dichloroisothiazole and any one or two of commercial acaricides form an acaricidal composition for preventing and controlling agricultural and forestry and horticultural plant acarids, and the commercial acaricides are selected from the following groups: dichlorvos, heptenophos, metophos, dibromophos, pirimiphos-methyl, ethion, chlorfenvinphos, vofenphos, pirimiphos-methyl, quinalphos, aphidmethomyl, amicarbaz, chlorfenphos, phosmet, fluthrin, bifenthrin, cyhalothrin, lambda-cyhalothrin, fenpropathrin, bifenazate, fenobucarb, butoxycarb, oxamyl, carbofuran, monocarb, benomyl, cloxacarb, butathion, lufenuron, benzoate, bromopropylate, cyflumetofen, flufenpyr, flufenoxuron, chlorfenapyr, sumicin, miticide, ruscin, avermectin, doramectin, norubicin, eprinomectin, ivermectin, larmectin, moxidectin, chrysanthemin, nicotine, alkali, dimethomorphin, chlorfenapyr, Nimbin, rotenone, tebufenpyrad, pyridaben, fenpyroximate, clofentezine, propargite, hexythiazox, spirodiclofen, fluacrypyrim, acaricide, propargite and pyridaben; the total mass percentage of the coumarin derivative I containing 3, 4-dichloroisothiazole in the acaricidal composition is 1% -90%, and the ratio of the coumarin derivative I containing 3, 4-dichloroisothiazole to the commercial acaricide is 1% to 99% to 1% 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, 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 controlling 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 coumarin derivatives containing 3, 4-dichloroisothiazole. The derivative can regulate and control the biological activity 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 1 chemical structure and physicochemical parameters of 3, 4-dichloroisothiazole-containing coumarin derivatives I of the present invention
Table 2 bacteriostatic activity of 3, 4-dichloroisothiazole-containing coumarin derivatives I of the present invention (inhibition rate of 50 μ g/ml/%)
| Serial number | Compound (I) | R.c | P.p | S.s | G.z | B.c | P.i | C.a | A.s | P.s |
| 1 | LY01-43 | 100 | 98 | 78 | 86 | 87 | 84 | 92 | 77 | 89 |
| 2 | LY01-98 | 100 | 91 | 65 | 81 | 83 | 75 | 79 | 73 | 71 |
| 3 | LY01-99 | 100 | 100 | 87 | 98 | 98 | 92 | 81 | 78 | 87 |
| 4 | LY01-102 | 80 | 32 | 51 | 53 | 60 | 20 | 71 | 43 | 24 |
| 5 | LY01-107 | 48 | 41 | 52 | 31 | 13 | 25 | 28 | 10 | 22 |
| 6 | LY02-1 | 98 | 98 | 98 | 92 | 95 | 84 | 92 | 80 | 85 |
| 7 | LY02-2 | 98 | 93 | 78 | 77 | 85 | 84 | 84 | 70 | 83 |
| 8 | LY02-3 | 98 | 98 | 95 | 98 | 95 | 90 | 81 | 78 | 87 |
| 9 | LY02-5 | 96 | 98 | 98 | 75 | 92 | 75 | 95 | 68 | 75 |
| 10 | LY02-6 | 98 | 76 | 96 | 86 | 92 | 79 | 81 | 80 | 79 |
| 11 | LY02-7 | 98 | 96 | 77 | 94 | 92 | 84 | 87 | 78 | 85 |
| 12 | LY02-8 | 98 | 87 | 62 | 67 | 82 | 84 | 68 | 73 | 83 |
| 13 | LY02-12 | 98 | 98 | 83 | 85 | 95 | 84 | 79 | 75 | 81 |
| 14 | LY02-13 | 65 | 34 | 58 | 30 | 45 | 23 | 41 | 28 | 22 |
| 15 | LY02-14 | 98 | 93 | 95 | 83 | 92 | 68 | 81 | 70 | 68 |
| 16 | LY02-15 | 98 | 93 | 71 | 83 | 90 | 87 | 81 | 65 | 85 |
| 17 | LY02-16 | 98 | 87 | 67 | 78 | 85 | 81 | 73 | 70 | 81 |
| 18 | LY02-18 | 60 | 31 | 71 | 55 | 47 | 32 | 33 | 15 | 24 |
| 19 | LY02-19 | 96 | 86 | 94 | 72 | 85 | 68 | 76 | 70 | 66 |
| 20 | LY02-39 | 98 | 96 | 82 | 92 | 85 | 84 | 92 | 78 | 83 |
| 21 | LY02-40 | 73 | 35 | 21 | 50 | 88 | 38 | 52 | 30 | 24 |
| 22 | LY02-41 | 90 | 85 | 96 | 92 | 93 | 78 | 97 | 68 | 77 |
| 23 | LY02-47 | 100 | 98 | 95 | 85 | 90 | 81 | 95 | 88 | 79 |
| 24 | Kresoxim-methyl | 56 | 69 | 92 | 68 | 26 | 60 | 54 | 42 | 64 |
| 25 | Pyraclostrobin (Kresoxim-methyl) | 80 | 81 | 100 | 86 | 90 | 62 | 83 | 70 | 66 |
| 26 | Boscalid | 67 | 67 | 96 | 44 | 100 | 37 | 100 | 100 | 37 |
| 27 | Pyrazolonaphthioides | 73 | 88 | 94 | 21 | 100 | 54 | 100 | 96 | 48 |
R.c: rhizoctonia cerealis, with the latin name: rhizoctonia cere, P.p: apple ring rot, its latin name is: physiosporia piricola, S.s: sclerotinia sclerotiorum, its latin name is: sclerotina sclerotomalis, G.z: wheat scab, its latin name is: gibberella zeae, b.c: the cucumber botrytis cinerea with the latin name as follows: botrytis cinerea, P.i: the late blight of potato, its latin name is: phytophthora infestans (Mont.) de barr, C.a: peanut brown spot pathogen, its latin name is: cercospora arachidicola, A.s: tomato early blight, its latin name is: alternaria solani, P.s: rhizoctonia solani, the Latin name of which is: pellieularia sasaikii.
Claims (7)
1. The coumarin derivatives containing 3, 4-dichloroisothiazole are characterized by simultaneously containing 3, 4-dichloroisothiazole heterocycle and 7-position or 5-position hydroxycoumarin structure, and have a structural general formula shown in a formula I:
wherein R is1Selected from: hydrogen, methyl, chlorine; r2Selected from: hydrogen, methyl, ethyl, fluorine, chlorine.
2. The specific synthetic route and method of the 3, 4-dichloroisothiazole-containing coumarin derivative I according to claim 1 are as follows:
the definition of the substituent is as defined in claim 1, and the specific synthetic method comprises the following steps:
synthesizing a coumarin derivative I containing 3, 4-dichloroisothiazole:
3, 4-dichloroisothiazole-beta-keto ester 1(1.0 mmol) and substituted resorcinol 2(1.1 mmol) were dispersed in dry trifluoroacetic acid (2.0 ml) and the solution was stirred at room temperature; heating and refluxing for 2-12 hours; after the thin-layer chromatography detection reaction is finished, concentrating the reaction solution, adding ethyl acetate (10 ml) and water (10 ml), stirring, standing and layering, extracting the water phase with ethyl acetate (2X 10 ml), combining the organic phases, washing the organic phases with saturated sodium bicarbonate solution, water and saturated salt solution in turn, and adding anhydrous sodium sulfate for drying; vacuum filtering, concentrating, and performing column chromatography (V)Petroleum ether∶VEthyl acetatePurifying the obtained product at a ratio of 10: 1-3: 1) to obtain a coumarin derivative I containing 3, 4-dichloroisothiazole; amount and reaction volume for the preparation of Compound IThe volume of the device is enlarged or reduced according to the corresponding proportion; the substituents are as defined in claim 1.
3. Use of the 3, 4-dichloroisothiazole-containing coumarin derivative I according to claim 1 for preparing agricultural fungicides.
4. An agricultural fungicidal composition comprising the 3, 4-dichloroisothiazole-containing coumarin derivative I according to claim 1 and an intermediate, wherein the agricultural fungicidal composition comprises the 3, 4-dichloroisothiazole-containing coumarin derivative I according to 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 coumarin derivative I containing 3, 4-dichloroisothiazole and other commercial bactericides as claimed in claim 1 as active ingredients, wherein the proportion of the coumarin derivative I containing 3, 4-dichloroisothiazole and other commercial bactericides is 1% to 99% to 1% by mass, the content of the active ingredients is 1 to 99% by weight, and the solid or liquid auxiliary agent is 99 to 1% by weight.
6. An agricultural insecticidal and acaricidal compound composition, which comprises the coumarin derivative I containing 3, 4-dichloroisothiazole as claimed in claim 1 and other commercial insecticidal and acaricidal agents as active ingredients, wherein the insecticidal and acaricidal ratio of the coumarin derivative I containing 3, 4-dichloroisothiazole to the other commercial insecticidal and acaricidal agents is 1% to 99% to 1% by mass, the content of the active ingredients is 1 to 99% by weight, and the content of the solid or liquid auxiliaries is 99 to 1% by weight.
7. A compound composition of an anti-plant virus agent comprises the coumarin derivative I containing 3, 4-dichloroisothiazole and other commercial anti-plant virus agents, wherein the coumarin derivative I containing 3, 4-dichloroisothiazole and the other commercial anti-plant virus agents are compounded to serve as active ingredients, the mass percentage of the coumarin derivative I containing 3, 4-dichloroisothiazole to the other commercial anti-plant virus agents is 1: 99-99: 1%, the content of the active ingredients is 1-99% by weight, and 99-1% by weight of solid or liquid auxiliaries.
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| CN113767923A (en) * | 2021-09-13 | 2021-12-10 | 广西壮族自治区亚热带作物研究所（广西亚热带农产品加工研究所） | Novel chemical agent for preventing and treating tea yellow mites |
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| CN113767923A (en) * | 2021-09-13 | 2021-12-10 | 广西壮族自治区亚热带作物研究所（广西亚热带农产品加工研究所） | Novel chemical agent for preventing and treating tea yellow mites |
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