CN113929697B - 1,3, 4-Oxadiazole psoralen derivatives, and preparation method and application thereof - Google Patents

1,3, 4-Oxadiazole psoralen derivatives, and preparation method and application thereof Download PDF

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CN113929697B
CN113929697B CN202111351143.3A CN202111351143A CN113929697B CN 113929697 B CN113929697 B CN 113929697B CN 202111351143 A CN202111351143 A CN 202111351143A CN 113929697 B CN113929697 B CN 113929697B
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oxadiazole
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psoralen
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CN113929697A (en
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范志金
董静月
洪泽宇
李坤
高卫
陈蕾
唐良富
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Nankai University
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D493/00—Heterocyclic compounds containing oxygen atoms as the only ring hetero atoms in the condensed system
    • C07D493/02—Heterocyclic compounds containing oxygen atoms as the only ring hetero atoms in the condensed system in which the condensed system contains two hetero rings
    • C07D493/04—Ortho-condensed systems
    • 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
    • A01N43/90—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having two or more relevant hetero rings, condensed among themselves or with a common carbocyclic ring system

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Abstract

The invention provides 1,3, 4-oxadiazole psoralen derivatives, a preparation method and application thereof, and in particular relates to 1,3, 4-oxadiazole psoralen derivatives, the chemical structural general formula of which is shown in formula l:

Description

1,3, 4-Oxadiazole psoralen derivatives, 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 1,3, 4-oxadiazole psoralen compound, and a preparation method and application thereof.
Background
Plant-derived pesticides have been the hotspot in the research of new pesticides as part of biorational pesticides. The botanical pesticide can degrade in nature and generally does not pollute the environment and agricultural products. The possibility of toxicity accumulation in the environment and human body is low, the agricultural product is relatively safe to human and livestock, has the characteristics of low toxicity and low residue, and can keep the high quality of the agricultural product (Li Xiaofei and the like. Southern agriculture, 2018, 12 (13): 40-42, 45.). The psoralen is used as an important plant source medicine intermediate, and has wide application value in the fields of food, medicine, pesticide and the like. The agricultural bactericide prepared by taking the psoralen as the active ingredient has excellent bactericidal activity, can be applied to preventing and treating diseases of various crops, is particularly suitable for preventing and treating agricultural fungal diseases such as sclerotinia rot of colza, sheath blight of rice, scab of wheat and the like, and is an ideal bactericide in agriculture.
The heterocyclic compound contains atoms such as nitrogen, oxygen, sulfur and the like, has high-efficiency, low-toxicity and broad-spectrum biological activity, and plays an important role in the design and synthesis of novel green pesticides. The literature reports that five-membered heterocyclic compounds have various activities such as insect disinfestation, bacteriostasis, weeding, plant growth regulation and the like (Chen Danping, modern pesticides, 2014, 14 (2): 5-10.); wherein, 1,3, 4-oxadiazole is used as a common nitrogen-containing five-membered heterocycle, has good biological activity and pharmacological activity, such as anti-tumor, anti-HIV, anticonvulsive, anti-virus, insecticidal, weeding, sterilization and the like, and is widely applied to the fields of pesticides, medicines and the like (Yang Zihui and the like. Kunming university school of medicine 2017, 39 (6): 85-88). For example, the herbicide oxadiazon can effectively prevent and kill various annual monocotyledonous and dicotyledonous weeds, and the pesticide oxadiazon has contact or stomach poisoning effect on insects, and can be used for preventing and controlling pests such as cockroaches, aphids, leafhoppers and the like. In addition, it has excellent electron injection and transport functions and is widely used in organic electroluminescent materials. And the parent nucleus structure has hydrogen bond receptor characteristics, and can effectively improve the lipophilicity and the toxicological and pharmacokinetics characteristics of the drug, so that the 1,3, 4-oxadiazole structure is still often selected as an effective active group in the creation of new pesticides.
In order to find and discover pesticide lead and candidate compounds which are more efficient, broad-spectrum, low in toxicity and ecological risk and have no interactive resistance, the invention introduces a1, 3, 4-oxadiazole structure into a lead structure of psoralen, designs and synthesizes a class of 1,3, 4-oxadiazole psoralen derivatives, and screens and evaluates the biological activity of the system.
Disclosure of Invention
The technical problems to be solved by the invention are as follows: provides a novel synthesis method of 1,3, 4-oxadiazole psoralen derivatives, provides biological activities of the compounds for regulating and controlling agricultural, horticultural and hygienic plant pests and plant pathogens in forestry and a determination method thereof, and 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 1,3, 4-oxadiazole psoralen compound with insecticidal, acaricidal, bactericidal, anti-plant virus and induced plant disease resistance activity in the agricultural field, the horticultural field and the forestry field is shown as I:
Wherein R 1 is selected from: hydrogen, 4-fluoro; r 2 is selected from: 4-methylbenzyl, 4-fluorobenzyl, 3-methylbenzyl, 4-nitrobenzyl, o-methylbenzyl, 4-chlorobenzyl, propargyl, 4-iodobenzyl, n-propyl, 2-naphthylmethyl, allyl, 2, 4-dichlorobenzyl, 4-tert-butylbenzyl, cyclopropylmethyl, 4-chlorobenzoylmethyl, 2-cyano-5-pyridylmethyl, 3-bromobenzyl, (E) -2- (2-methoxy-1- (methoxyimino) -2-oxoethyl) benzyl, (E) -2- (1, 3-dimethoxy-3-oxoprop-1-en-2-yl) benzyl, 3-methylbut-2-enyl, benzoylmethyl, 4-trifluoromethoxybenzyl, 2- (4-chlorophenyl) ethyl.
The synthetic route of the 1,3, 4-oxadiazole psoralen derivative I and the intermediate thereof is as follows:
The synthesis method of the 1,3, 4-oxadiazole psoralen derivative I comprises the following steps:
A. preparation of compound 3:
Adding the compound 1 into a reaction bottle, adding the compound 2, then slowly dropwise adding 98% concentrated sulfuric acid under stirring, and stirring at room temperature; after the reaction is finished, adding a proper amount of methanol, then pouring the methanol into ice water to generate a large amount of white solid, and carrying out suction filtration and drying to obtain a compound 3;
B. Preparation of compound 5:
Taking a compound 3, adding a proper amount of anhydrous acetonitrile into a reaction bottle, then sequentially adding potassium carbonate, potassium iodide and a compound 4 under stirring, and heating and refluxing; after the reaction is finished, removing most acetonitrile under reduced pressure, adding water and ethyl acetate for extraction, washing an organic phase with saturated sodium chloride solution, drying with anhydrous sodium sulfate, carrying out vacuum filtration, concentrating filtrate to remove solvent, and purifying by column chromatography to obtain a compound 5;
C. preparation of Compound 6:
Adding a proper amount of isopropanol into a reaction bottle, slowly dropwise adding 1 mol/L sodium hydroxide solution under stirring, and heating for reflux; after the reaction is finished, removing most of isopropanol under reduced pressure, regulating the pH value of a system to be 1-2 by using 1 mol/L hydrochloric acid solution, and carrying out suction filtration and drying on the generated solid to obtain a compound 6;
D. preparation of compound 7:
Taking a compound 6, adding a proper amount of absolute methanol into a reaction bottle, then slowly dropwise adding 98% concentrated sulfuric acid under stirring, and heating and refluxing; after the reaction is finished, removing most of methanol under reduced pressure, adding water and ethyl acetate into residues for extraction, washing an organic phase with saturated sodium chloride solution, drying with anhydrous sodium sulfate, carrying out vacuum filtration, concentrating filtrate to remove solvent, and purifying by column chromatography to obtain a compound 7;
E. preparation of Compound 8:
Taking a compound 7, adding a proper amount of methanol into a reaction bottle, slowly dropwise adding 80% hydrazine hydrate under stirring, and heating and refluxing; after the reaction is finished, removing most of methanol under reduced pressure, adding water and ethyl acetate into residues for extraction, washing an organic phase with saturated sodium chloride solution, drying with anhydrous sodium sulfate, carrying out reduced pressure suction filtration, concentrating filtrate to remove solvent, and purifying by column chromatography to obtain a compound 8;
F. Preparation of Compound 9:
Adding a proper amount of absolute ethyl alcohol into a reaction bottle, adding potassium hydroxide under stirring, slowly dripping carbon disulfide, and heating for reflux; after the reaction is finished, removing most of ethanol under reduced pressure, adding 1mol/L hydrochloric acid solution into residues to adjust the pH value of a system to be 1-2, extracting ethyl acetate, washing an organic phase with saturated sodium chloride solution, drying with anhydrous sodium sulfate, carrying out vacuum filtration, concentrating filtrate to remove a solvent, and purifying by column chromatography to obtain a compound 9;
G. preparation of Compound I-a:
Adding a proper amount of N, N-dimethylformamide into a reaction bottle, sequentially adding potassium hydroxide, chlorinated hydrocarbon or brominated hydrocarbon, and stirring at room temperature; after the reaction is finished, adding a proper amount of water and ethyl acetate for extraction, washing an organic phase with a saturated sodium chloride solution, drying with anhydrous sodium sulfate, carrying out vacuum filtration, concentrating filtrate to remove a solvent, and purifying by column chromatography to obtain the compound I-a;
H. Preparation of Compound I-b:
Under the low-temperature ice bath condition, taking a compound I-a, adding a proper amount of dichloromethane into a reaction bottle, then slowly dropwise adding a dichloromethane solution in which m-chloroperoxybenzoic acid is dissolved, and moving the system to room temperature for stirring; after the reaction is finished, removing most of dichloromethane under reduced pressure, adding a proper amount of ethyl acetate into residues, washing with 0.25 mol/L disodium hydrogen phosphate solution and saturated sodium chloride solution in sequence, drying with anhydrous sodium sulfate, carrying out vacuum filtration, concentrating filtrate to remove solvent, and purifying by column chromatography to obtain a compound I-b;
I. Preparation of Compounds I-c:
under the low-temperature ice bath condition, taking a compound I-a, adding a proper amount of acetic acid into a reaction bottle, slowly dropwise adding a hydrogen peroxide solution in which ammonium molybdate is dissolved under stirring, and then moving the system to room temperature for stirring; after the reaction is finished, adding water and ethyl acetate for extraction, washing an organic phase by using a saturated sodium bisulfate solution and a saturated sodium chloride solution in sequence, drying by using anhydrous sodium sulfate, carrying out vacuum filtration, concentrating filtrate to remove a solvent, and purifying by column chromatography to obtain a compound I-c;
as a preferred embodiment, the synthesis method of the 1,3, 4-oxadiazole psoralen derivatives comprises the following steps:
A. preparation of compound 3:
Into a 100 ml round bottom flask were added 18.2 mmol resorcinol and 18.2 mmol dimethyl acetylsuccinate followed by slowly dropwise adding 2.73 ml 98% concentrated sulfuric acid with stirring, after which the reaction was stirred at room temperature overnight. Monitoring TLC, adding 30 ml of absolute methanol after the reaction is finished, pouring the absolute methanol into ice water to generate a large amount of white solid, filtering the solid, washing a crude product with diethyl ether, and recrystallizing the crude product with ethanol-water to obtain a compound 3; the amount of compound 3 prepared and the volume of the reaction vessel are scaled up or down accordingly.
B. Preparation of compound 5:
to a 100 ml round bottom flask were added 4.03 mmol of compound 3 and 30 ml of anhydrous acetonitrile, 4.836 mmol of compound 4, 16.12 mmol of anhydrous potassium carbonate and 0.403 mmol of potassium iodide in this order with stirring at room temperature, and then the reaction system was heated to reflux for 5 hours. TLC monitoring, standing and cooling to room temperature after the reaction is finished, decompressing and removing most of the solvent, adding 30 ml of water into the residue, extracting with ethyl acetate three times (15 ml multiplied by 3), washing the organic phase with saturated sodium chloride solution three times (15 ml multiplied by 3), and combining the organic layers and drying with anhydrous sodium sulfate; vacuum filtering, concentrating the filtrate to remove solvent, and purifying with petroleum ether/ethyl acetate (3:1, v/v) eluent column chromatography to obtain compound 5; the amount of compound 5 prepared and the volume of the reaction vessel are scaled up or down accordingly.
C. preparation of Compound 6:
Into a 100 ml round bottom flask were added 1g of compound 5 and 30ml of isopropanol, 30ml of 1 mol/l sodium hydroxide solution was slowly added dropwise with stirring at room temperature, and the reaction system was heated under reflux for 4 hours after the addition. Monitoring by TLC, standing the system after the reaction is finished, cooling to room temperature, decompressing and removing most of isopropanol, adding 1 mol/L hydrochloric acid solution into the remainder to adjust the pH value of the system to be 1, precipitating a large amount of solids, carrying out suction filtration and drying to obtain a compound 6; the amount of compound 6 prepared and the volume of the reaction vessel are scaled up or down accordingly.
D. preparation of compound 7:
1 g of Compound 6 and 30 ml of absolute methanol are added into a 100ml round-bottom flask, 1.5 ml of 98% concentrated sulfuric acid is slowly added dropwise under stirring at room temperature, and the reaction system is heated and refluxed for 5 hours after the addition. Monitoring by TLC, standing the system after the reaction is finished, cooling to room temperature, removing most of methanol under reduced pressure, adding 30 ml of water into the residue, extracting with ethyl acetate three times (15 ml×3), washing the organic phase with saturated sodium chloride solution three times (15 ml×3), and drying the combined organic layer with anhydrous sodium sulfate; vacuum filtering, concentrating the filtrate to remove solvent, and purifying with petroleum ether/ethyl acetate (3:1, v/v) eluent column chromatography to obtain compound 7; the amount of compound 7 prepared and the volume of the reaction vessel are scaled up or down accordingly.
E. preparation of Compound 8:
1 mmol of Compound 7 and 30ml of methanol were charged into a 100 ml round-bottom flask, 4 mmol of 80% hydrazine hydrate was slowly added dropwise with stirring at room temperature, and the reaction system was heated under reflux for 8 hours after the addition was completed. Monitoring by TLC, standing the system after the reaction is finished, cooling to room temperature, removing most of methanol under reduced pressure, adding 30ml of water into the residue, extracting with ethyl acetate three times (15 ml×3), washing the organic phase with saturated sodium chloride solution three times (15 ml×3), and drying the combined organic layer with anhydrous sodium sulfate; vacuum filtering, concentrating the filtrate to remove solvent, and purifying by column chromatography with dichloromethane/methanol (15:1, v/v) eluent to obtain compound 8; the amount of compound 8 prepared and the volume of the reaction vessel are scaled up or down accordingly.
F. Preparation of Compound 9:
1 mmol of Compound 8 and 20 ml of absolute ethanol were added to a 100 ml round bottom flask, 1.2 mmol of potassium hydroxide was added with stirring at room temperature, 3 mmol of carbon disulfide was slowly added after 5 minutes, and then the reaction was heated under reflux for 6 hours. Monitoring by TLC, standing the system, cooling to room temperature after the reaction is finished, decompressing and removing most of ethanol, adding 15 ml of water into the residue, adjusting the pH value of the system to be 1-2 by using 1 mol/l hydrochloric acid solution, extracting three times (15 ml multiplied by 3) by ethyl acetate, washing the organic phase three times (15 ml multiplied by 3) by using saturated sodium chloride solution, and drying the combined organic layer by using anhydrous sodium sulfate; vacuum filtering, concentrating the filtrate to remove solvent, and purifying by column chromatography with dichloromethane/methanol (17:1, v/v) eluent to obtain compound 9; the amount of compound 9 prepared and the volume of the reaction vessel are scaled up or down accordingly.
G. preparation of Compound I-a:
To a 100 ml round bottom flask were added 1 mmol of compound 9 and 20 ml of N, N-dimethylformamide, 2.3 mmol of potassium hydroxide and 1.2 mmol of bromohydrocarbon or chlorohydrocarbon in this order with stirring at room temperature, and then the reaction system was stirred at room temperature for 8 hours. TLC was monitored, after completion of the reaction, 15ml of water was added, extraction was performed three times with ethyl acetate (15 ml×3), the organic phase was washed three times with saturated sodium chloride solution (15 ml×3), and the combined organic layers were dried over anhydrous sodium sulfate; vacuum filtering, concentrating the filtrate to remove solvent, and purifying by column chromatography with dichloromethane/methanol (30:1, volume/volume) eluent to obtain compound I-a; the amount of compound I-a prepared and the volume of the reaction vessel are scaled up or down accordingly.
H. Preparation of Compound I-b:
1 mmol of Compound I-a and 20 ml of methylene chloride were charged into a 100 ml round bottom flask under ice bath at low temperature, 1.6 mmol of m-chloroperoxybenzoic acid was slowly added with stirring, and then the reaction system was allowed to stand at room temperature for reaction for 6 hours. After the completion of the reaction, most of methylene chloride was removed under reduced pressure by TLC, the reaction was extracted three times with ethyl acetate (15 ml. Times.3), the organic phase was washed three times with 0.25 mol/L disodium hydrogen phosphate solution (15 ml. Times.3) and saturated sodium chloride solution (15 ml. Times.3), and the combined organic layers were dried over anhydrous sodium sulfate; vacuum filtering, concentrating the filtrate to remove solvent, and purifying by column chromatography with dichloromethane/methanol (40:1, volume/volume) eluent to obtain compound I-b; the amount of compound I-b prepared and the volume of the reaction vessel are scaled up or down accordingly.
I. Preparation of Compounds I-c:
Under the condition of low-temperature ice bath, 1 mmol of compound I-a and 20 ml of anhydrous acetic acid are added into a 100 ml round bottom flask, a 30% hydrogen peroxide solution with 0.05 mmol of ammonium molybdate dissolved therein and 6mmol of the solution are slowly added dropwise under stirring, and then the reaction system is moved to room temperature for reaction for 8 hours. After the completion of the reaction, 15 ml of water was added and extracted three times with ethyl acetate (15 ml×3), and the organic phase was washed three times with a saturated sodium bisulfate solution (15 ml×3) and a saturated sodium chloride solution (15 ml×3) in this order, and the combined organic layers were dried over anhydrous sodium sulfate; vacuum filtering, concentrating the filtrate to remove solvent, and purifying with dichloromethane/methanol (20:1, volume/volume) eluent column chromatography to obtain compound I-c; the amount of compound I-c prepared and the volume of the reaction vessel are scaled up or down accordingly.
Wherein R 1 is selected from: hydrogen, 4-fluoro; r 2 is selected from: 4-methylbenzyl, 4-fluorobenzyl, 3-methylbenzyl, 4-nitrobenzyl, o-methylbenzyl, 4-chlorobenzyl, propargyl, 4-iodobenzyl, n-propyl, 2-naphthylmethyl, allyl, 2, 4-dichlorobenzyl, 4-tert-butylbenzyl, cyclopropylmethyl, 4-chlorobenzoylmethyl, 2-cyano-5-pyridylmethyl, 3-bromobenzyl, (E) -2- (2-methoxy-1- (methoxyimino) -2-oxoethyl) benzyl, (E) -2- (1, 3-dimethoxy-3-oxoprop-1-en-2-yl) benzyl, 3-methylbut-2-enyl, benzoylmethyl, 4-trifluoromethoxybenzyl, 2- (4-chlorophenyl) ethyl.
The invention provides application of the 1,3, 4-oxadiazole psoralen derivatives I in preparing fungicides.
The invention provides application of the 1,3, 4-oxadiazole psoralen derivative I in preparing a tobacco mosaic virus resisting agent.
The invention provides application of the 1,3, 4-oxadiazole psoralen derivative I in preparation of a plant activator for inducing tobacco to resist tobacco mosaic virus.
The invention provides application of the 1,3, 4-oxadiazole psoralen derivatives I in preventing and controlling insect pests of agricultural and forestry and horticultural plants.
The 1,3, 4-oxadiazole psoralen derivatives I and agricultural chemicals are applied together; the agricultural chemical is selected from: one or more of insecticide, bactericide, plant virus resisting agent and acaricide.
The 1,3, 4-oxadiazole psoralen derivative I and any one or two of the pesticides are combined to form an insecticidal composition which is used for preventing and controlling insect pests of agriculture, forestry and horticulture plants;
The insecticide is selected from: bifenthrin, permethrin, ethofenprox, flumethrin, fluramid, imidacloprid nitenpyram, imidaclothiz, thiacloprid, thiamethoxam, clothianidin, dinotefuran, collidine bifenthrin, permethrin, ethofenprox, flumethrin, fluramid, 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, fenoxacarb, fenoxaprop-p-ethyl, pyridalyl, clomazone, clofentezine, propargite, diafenthiuron, pymetrozine, spirodiclofen, spirotetramat, azocyclotin, buprofezin, monosultap, chlorfenapyr, tetrachlorethamide, flufenamid, cyanogen, butene fipronil, tolfenpyrad, chlorfenapyr, pyrazinone, etoxazole, tebufenpyrad, pyridaben, pyrifos, tebufenozide;
The mass percentage content of the 1,3, 4-oxadiazole psoralen derivatives I in the insecticidal composition is 1% -90%; preferably, the ratio of the 1,3, 4-oxadiazole psoralen derivatives I to the insecticide is 1 to 99 percent by mass 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, white fly, bemisia tabaci, black tail leafhopper, green 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, mealy bugs, sang Dun scale, sagittaria verrucosa, piricosa, meadow wax beetles, korean ball mealy bugs, pear net bugs, banana net bugs, lygus lucorum, small flower bugs, needle-border bugs, rice spider border bugs, brown bugs, rice black bugs, green bugs, alfalfa bugs, medium black bugs, chrysopa, lilaces, chinese chrysopa, moth, clothes moths, yellow thorns, brown moths, flat moths 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 leaf roller 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, 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, chest needle worm, valley bark beetle, black bark beetle, citrus gill worm, jin Yuanji budworm, yellow meal worm, black meal worm, red-yellow larch, hybrid-yellow larch, copper green-yellow larch, dark-black tortoise, giant-black gill-white tortoise, mulberry longhorn, star longhorn, orange-brown longhorn, peach-red longhorn, great ape leaf worm, small ape leaf worm, yellow-head melon, yellow-curved striped flea, green bean image, pea image, broad bean image, corn image, rice image, wheat leaf bee, pear-fruit bee, yellow-banded cornflower, armyworm white star-cornflower, boll fly-hanging cornflower, cotton bollworm tooth-lip cornflower, borer black spot wart, mosquito, fly, horsefly, wheat red-sucking maggot, wheat Huang Xi thick beetle, rice gall midge, citrus fruit fly, melon fruit fly, wheat She Hui fly, american leaf fly, bean stalk black fly, wheat fly, seed fly, onion fly, radish fly, umbrella-skirt, corn borer, myalid 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 1,3, 4-oxadiazole psoralen derivative I and any one or two of the bactericides are combined to form a bactericidal composition for preventing and controlling plant diseases of agriculture, forestry and gardening;
The bactericide is selected from the group consisting of: benzothiadiazole, tiadinil, thiabendazole, methidathiamide, 4-methyl-1, 2, 3-thiabendazole-5-carboxylic acid, sodium 4-methyl-1, 2, 3-thiabendazole-5-carboxylate, ethyl 4-methyl-1, 2, 3-thiabendazole-5-carboxylate, DL-beta-aminobutyric acid, isothiabendazole, 3, 4-dichloroisothiazole-5-carboxylic acid, sodium 3, 4-dichloroisothiazole-5-carboxylate, ethyl 3, 4-dichloroisothiazole-5-carboxylate, ribavirin, antofen, ningnanmycin or salicylic acid, cymoxanil, thiram, ziram, mancozeb, fosetyl, thiophanate, chlorothalonil, difenoconazole, benomyl, fenpropizine, thiophanate, tolfenpropazine, triflumine, dimethomorph, high-efficiency mebendazole, mechlor, flufenamide, sulfenamide methanesulfonamide, thiabendazole, leaf-carrier, cyclopropylamide, cyflufenamid, cycloxaprid, fenhexamid, silthiopham, carboxin oxide, mefenoxam formamide, metolachlor, flufenamide, furametpyr, thifluzamide, boscalid, penthiopyrad, isopyrazam, bixafen, fluopyram, flupyraclostrobin, flupyrad, flupyraclostrobin, flupirtine formamide, metolachlor, fluoamide, furametpyr, thifluzamide, boscalid, fluxapyroxad, fluzamide, fluxad, flud, penthiopyrad, isopyrazam, bixafen, fluopyram, trifloxystrobin, enestroburin, epoxiconazole, furfuryl azole, cyproconazole, difenoconazole, diniconazole, high-efficiency diniconazole, epoxiconazole, fenbuconazole, fluquinconazole, flusilazole, flutriafol, epoxiconazole, difenoconazole, propiconazole, epoxiconazole, hexaconazole, imibenconazole, ipconazole, metconazole, myclobutanil, penconazole, propiconazole, prothioconazole, simeconazole, tebuconazole, tetraconazole, triadimenol, triticonazole, bitertanol, thiabendazole, epoxiconazole, difenoconazole, tebuconazole, and the like corncob, imazalil, high-efficiency imazalil, prochloraz, triflumizole, cyazofamid, imidazolone, oxaimidazole, fenoxanil, famoxadone, oxadone, oxadixyl, ethaboxam, hymexazol, xin Sai ketone, benthiavalicarb-isopropyl, dode-morpholine, fenpropimorph, tridemorph, fenpiclonil, fludioxonil, fluazinam, pyripyroxim, cyprodinil, fluoxastrobin, cyprodinil fluoxastrobin, azoxystrobin, cyprodinil, pyrimethanil, chloropyrimol, flubenyrimol, fenamidone, dithianon, ethoxyquinoline, hydroxyquinoline, propiquin, phenoxyquinoline, diethofencarb, iprovalicarb, benthiavalicarb, propamocarb, sulfencarb, diphenfos, iprobenfos, pyrifos, tolclofos-methyl, blasticidin, kasugamycin, polyoxin, validamycin, streptomycin, metalaxyl, furalaxyl, benalaxyl, furalaxyl, carbendazim, benomyl, thiophanate-methyl, triazolone, bupirimate, dimethirimol, ethirimol, captan, folpet, ethephon, fluclomazone, dimethachlor, chlorothalonil, isoprothiolane, metconazole, pentachloronitrobenzene, propineb, triclophate, aluminum, sulphur, copper sulphate, copper chloride solution, chlorpyrifos, cuprous oxide, copper hydroxide, metrafenone, pencycuron, pyridazinone, tetrachlorophthalide, fluquindox, spiroxamine, tricyclazole, zinyl, dodine, guanamine, chlornitramine, bensulfenamide, indolyl ester, sodium disultone, quinocetone, probenazole, bronitol, methyl iodide, carb, diline ester, dazomet, diisopropyl ether, fosthiazate, fenitrothion, triazophos, carbosulfan, triadimefon, sulfuryl fluoride, dichloropropene, dichloroisonicotinic acid, and allylisothiazole;
The total mass percentage of the 1,3, 4-oxadiazole psoralen derivatives I in the bactericidal composition is 1% -90%; the mass percentage of the 1,3, 4-oxadiazole psoralen derivative I to the bactericide is 1 to 99 to 1 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 1,3, 4-oxadiazole psoralen derivative I and any one or two of the antiviral agents are combined to form an antiviral composition which is used for preventing and controlling agricultural and forestry and gardening plant virus diseases;
The antiviral agent is selected from: benzothiadiazole, tiadinil, isotiadinil, 4-methyl-1, 2, 3-thiadiazole-5-carboxylic acid, sodium 4-methyl-1, 2, 3-thiadiazole-5-carboxylate, ethyl 4-methyl-1, 2, 3-thiadiazole-5-carboxylate, 3, 4-dichloroisothiazole-5-carboxylic acid, sodium 3, 4-dichloroisothiazole-5-carboxylate, ethyl 3, 4-dichloroisothiazole-5-carboxylate, DL-beta-aminobutyric acid, 2, 6-dichloroisonicotinic acid, N-cyanomethyl-2-chloroisonicotinamide, allylisothiazole, ribavirin, antofine, ningnanmycin, thiamide, methiadipamide or salicylic acid, pyrimidone, dichloroisonicotinic acid, allylisothiazole, validoxylamine, validamycin, moroxydine hydrochloride;
The total mass percentage of the 1,3, 4-oxadiazole psoralen derivatives I in the antiviral composition is 1% -90%; preferably, the ratio of the 1,3, 4-oxadiazole psoralen derivatives I to the plant virus resisting agent is 1 percent to 99 percent 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.
Any one or two of the 1,3, 4-oxadiazole psoralen derivatives I and the acaricide are combined to form an acaricidal composition which is used for preventing and controlling mites of agricultural and forestry and horticultural plants;
The acaricide is selected from the group consisting of: dichlorvos, heptylphosphines, acephate, dibromophosphorus, pyrimidine phosphorus, chlormethiphos, ethion, chlorfenphos, vos methyl pyrifos, quetiapine, aphid, amifos, chlorimfos, iminofos, flumethrin, bifenthrin cyhalothrin, lambda-cyhalothrin, fenpropathrin, flumetofen, fenhexamid, fenfluramine, bifenthrin, benfuracarb, carbofuran, fenoxacarb, benomyl, clomazone, ding Liusu methomyl, fenbucarb, fenbucin 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 1,3, 4-oxadiazole psoralen derivatives I in the acaricidal composition is 1% -90%; the mass percentage of the 1,3, 4-oxadiazole psoralen derivative I to the acaricide is 1 to 99 to 1 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 biological activity of the 1,3, 4-oxadiazole psoralen derivatives I is measured as follows:
N. determination of bactericidal activity of 1,3, 4-oxadiazole psoralen derivatives I of the invention:
the bactericidal or bacteriostatic activity of the psoralen I containing 1,3, 4-oxadiazole adopts a thallus growth rate measuring method, and the specific steps are as follows: 1.8 mg of sample is dissolved in 2 drops of N, N-dimethylformamide, 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, the culture dish is uniformly shaken to prepare 50 micrograms/ml of medicament-containing flat plates, 1 ml of sterilized water is added to serve as blank control, a puncher with the diameter of 4mm is used for cutting a fungus disk along the outer edge of hypha, the fungus disk is moved onto the medicament-containing flat plates to be placed in an equilateral triangle shape, each treatment is repeated for 3 times, the culture dish is placed into a constant temperature incubator with the temperature of 24+/-1 ℃ for culture, the expansion diameter of each treatment fungus disk is investigated after the diameter of a control colony is expanded to be 2-3 cm, the average value is calculated, and compared with the blank control, and the sample strain is the species of most typical plant pathogenic bacteria actually generated in the agricultural production in China, and the code and name are as follows: AS: the Latin name of the early blight bacteria of tomato is: ALTERNARIA SOLANI, BC: the Latin name of the Botrytis cinerea is: botrytis cinerea, CA: peanut brown spot germ, its latin name is: cercospora arachidicola, GZ: the gibberella wheat germ has the Latin name: gibberella zeae, PP: apple ring rot germ, its latin name is: physalospora piricola, PS: rhizoctonia solani, its Latin name is: pellicularia sasakii, SS: sclerotinia sclerotiorum, the Latin name of which is: sclerotinia sclerotiorum.
The beneficial effects of the invention are as follows: the 1,3, 4-oxadiazole psoralen derivatives I are optimized in advance, and the 1,3, 4-oxadiazole psoralen derivatives are screened for antibacterial activity.
The synthesis and biological activity and application of the 1,3, 4-oxadiazole psoralen derivatives I are more specifically described by specific preparation and biological activity measurement examples, the examples are only used for specifically describing the invention and not limiting the invention, and particularly the biological activity is only used for illustrating but not limiting the patent, and the specific embodiments are as follows:
Example 1: preparation of compound 3:
Into a 100ml round bottom flask were added 18.2 mmol resorcinol and 18.2 mmol dimethyl acetylsuccinate followed by slowly dropwise adding 2.73 ml 98% concentrated sulfuric acid with stirring, after which the reaction was stirred at room temperature overnight. Monitoring TLC, adding 30 ml of absolute methanol after the reaction is finished, pouring the absolute methanol into ice water to generate a large amount of white solid, filtering the solid, washing a crude product with diethyl ether, and recrystallizing the crude product with ethanol-water to obtain a compound 3; yield 81%; the nuclear magnetic data were obtained by scaling up or down the volume of the reaction vessel and the amount of compound 3 prepared as follows ：1H NMR(400MHz,DMSO)δ10.50(s,1H),7.59(d,J＝8.8Hz,1H),6.79(dd,J＝8.7,2.1Hz,1H),6.69(d,J＝2.1Hz,1H),3.61(s,2H),3.57(s,3H),2.30(s,3H)..
Example 2: preparation of compound 5:
To a 100 ml round bottom flask were added 1 mmol of compound 3 and 30ml of anhydrous acetonitrile, and 1.2 mmol of compound 4, 4 mmol of anhydrous potassium carbonate and 0.1 mmol of potassium iodide were sequentially added with stirring at room temperature, followed by heating and refluxing the reaction system for 5 hours. TLC monitoring, standing and cooling to room temperature after the reaction is finished, decompressing and removing most of acetonitrile, adding 30ml of water into the residue, extracting with ethyl acetate three times (15 ml multiplied by 3), washing an organic phase three times (15 ml multiplied by 3) with saturated sodium chloride solution, and combining organic layers and drying with anhydrous sodium sulfate; vacuum filtering, concentrating the filtrate to remove solvent, and purifying with petroleum ether/ethyl acetate (3:1, v/v) eluent column chromatography to obtain compound 5; the yield thereof was found to be 65%; the nuclear magnetic data were obtained by scaling up or down the volume of the reaction vessel and the amount of compound 5 prepared as follows ：1H NMR(400MHz,DMSO)δ8.12(s,2H),7.74(d,J＝8.8Hz,1H),7.42(t,J＝8.5Hz,2H),7.10(s,1H),7.04(d,J＝8.7Hz,1H),5.73(s,2H),3.67(s,2H),3.62(s,3H),2.38(s,3H)..
Example 3: preparation of Compound 6:
Into a 100 ml round bottom flask, 2g of compound 5 and 30 ml of isopropyl alcohol were charged, 60 ml of 1 mol/l sodium hydroxide solution was slowly added dropwise with stirring at room temperature, and the reaction system was heated under reflux for 4 hours after the addition. Monitoring by TLC, standing the system after the reaction is finished, cooling to room temperature, decompressing and removing most of isopropanol, adding 1 mol/L hydrochloric acid solution into the remainder to adjust the pH value of the system to be 1, precipitating a large amount of solids, carrying out suction filtration and drying to obtain a compound 6; yield 61%; the nuclear magnetic data were obtained by scaling up or down the volume of the reaction vessel and the amount of compound 6 prepared as follows ：1H NMR(400MHz,DMSO)δ12.29(s,1H),8.30(s,1H),7.98(s,1H),7.70(s,1H),7.61(s,1H),7.22(s,2H),3.49(s,2H),2.36(s,3H)..
Example 4: preparation of compound 7:
1g of Compound 6 and 30 ml of absolute methanol are added into a 100 ml round-bottomed flask, 1.5ml of 98% concentrated sulfuric acid is slowly added dropwise under stirring at room temperature, and the reaction system is heated under reflux for 6 hours after the addition. Monitoring by TLC, standing the system after the reaction is finished, cooling to room temperature, removing most of methanol under reduced pressure, adding 15 ml of water into the residue, extracting with ethyl acetate three times (15 ml multiplied by 3), washing the organic phase with saturated sodium chloride solution three times (15 ml multiplied by 3), and combining the organic layers to be dried with anhydrous sodium sulfate; vacuum filtering, concentrating the filtrate to remove solvent, and purifying with petroleum ether/ethyl acetate (3:1, v/v) eluent column chromatography to obtain compound 7; yield 79%; the nuclear magnetic data were obtained by scaling up or down the volume of the reaction vessel and the amount of compound 7 prepared as follows ：1H NMR(400MHz,DMSO)δ8.47(s,1H),8.17(s,1H),7.87(dd,J＝8.7,5.5Hz,2H),7.80(s,1H),7.38(t,J＝8.8Hz,2H),3.75(s,2H),3.63(s,3H),2.55(s,3H)..
Example 5: preparation of Compound 8:
1 mmol of Compound 7 and 30 ml of methanol were charged into a 100 ml round-bottom flask, 4 mmol of 80% hydrazine hydrate was slowly added dropwise with stirring at room temperature, and the reaction system was heated under reflux for 6 hours after the addition was completed. Monitoring by TLC, standing the system after the reaction is finished, cooling to room temperature, removing most of methanol under reduced pressure, adding 15 ml of water into the residue, extracting with ethyl acetate three times (15 ml multiplied by 3), washing the organic phase with saturated sodium chloride solution three times (15 ml multiplied by 3), and combining the organic layers to be dried with anhydrous sodium sulfate; vacuum filtering, concentrating the filtrate to remove solvent, and purifying by column chromatography with dichloromethane/methanol (15:1, v/v) eluent to obtain compound 8; the yield thereof was found to be 53%; the nuclear magnetic data were obtained by scaling up or down the volume of the reaction vessel and the amount of compound 8 prepared as follows ：1H NMR(400MHz,DMSO)δ9.18(s,1H),8.44(s,1H),8.09(s,1H),7.85(s,2H),7.73(s,1H),7.38(s,2H),4.30(s,2H),3.51(s,2H),3.41(s,3H)..
Example 6: preparation of Compound 9:
Into a 100 ml round bottom flask was added 0.2g of compound 8 and 20ml of absolute ethanol, 0.033 g of potassium hydroxide was added with stirring, 0.11 g of carbon disulphide was slowly added after 5 minutes, and then the reaction system was heated under reflux for 5 hours. Monitoring by TLC, standing the system, cooling to room temperature after the reaction is finished, decompressing and removing most of ethanol, adding 15 ml of water into the residue, adjusting the pH value of the system to be 1-2 by using 1 mol/l hydrochloric acid solution, extracting three times (15 ml multiplied by 3) by ethyl acetate, washing the organic phase three times (15 ml multiplied by 3) by using saturated sodium chloride solution, and drying the combined organic layer by using anhydrous sodium sulfate; vacuum filtering, concentrating the filtrate to remove solvent, and purifying by column chromatography with dichloromethane/methanol (17:1, v/v) eluent to obtain compound 9; the yield thereof was found to be 77%; the nuclear magnetic data were obtained by scaling up or down the volume of the reaction vessel and the amount of compound 9 prepared as follows ：1H NMR(400MHz,DMSO)δ14.40(s,1H),8.47(s,1H),8.18(s,1H),7.89-7.83(m,2H),7.80(s,1H),7.37(t,J＝8.6Hz,2H),4.15(s,2H),2.63(s,3H)..
Example 7: preparation of Compound I-a:
A100 ml round bottom flask was charged with 0.2 g of Compound 9 and 20ml of N, N-dimethylformamide, followed by 0.063 g of potassium hydroxide and 0.175 g of 4-iodobenzyl bromide with stirring, and the system was then stirred at room temperature for 8 hours. TLC was monitored, after completion of the reaction, 30ml of water was added, extraction was performed three times with ethyl acetate (15 ml×3), the organic phase was washed three times with saturated sodium chloride solution (15 ml×3), and the combined organic layers were dried over anhydrous sodium sulfate; vacuum filtering, concentrating the filtrate to remove solvent, and purifying by column chromatography with dichloromethane/methanol (30:1, volume/volume) eluent to obtain compound I-a; yield: 71-95%; when R 1 is 4-fluorophenyl and R 2 is 4-iodobenzyl, the nuclear magnetic data of the compound I-a-1 is that the prepared amount of the compound I-a-1 and the volume of the reaction vessel are enlarged or reduced according to corresponding proportions as follows ：1H NMR(400MHz,DMSO)δ8.40(s,1H),8.09(s,1H),7.84-7.77(m,2H),7.70(s,1H),7.55(d,J＝7.9Hz,2H),7.33(t,J＝8.6Hz,2H),7.15(d,J＝7.9Hz,2H),4.37(s,2H),4.22(s,2H),2.56(s,3H).; the physicochemical and structural parameters of compound I-a are shown in Table 1.
Example 8: preparation of Compound I-b:
In a 100ml round bottom flask, 0.58 g of compound I-a-1 and 20ml of methylene chloride were charged under ice bath at low temperature, 0.256 g of m-chloroperoxybenzoic acid was slowly added with stirring, and then the reaction system was allowed to stand at room temperature for reaction for 6 hours. After the completion of the reaction, most of methylene chloride was removed under reduced pressure by TLC, the reaction was extracted three times with ethyl acetate (15 ml. Times.3), the organic phase was washed three times with 0.25 mol/L disodium hydrogen phosphate solution (15 ml. Times.3) and saturated sodium chloride solution (15 ml. Times.3), and the combined organic layers were dried over anhydrous sodium sulfate; vacuum filtering, concentrating the filtrate to remove solvent, and purifying by column chromatography with dichloromethane/methanol (40:1, volume/volume) eluent to obtain compound I-b; yield: 65-91%; when R 1 is 4-fluorophenyl and R 2 is 4-iodobenzyl, the nuclear magnetic data of the compound I-b-1 is that the prepared amount of the compound I-b-1 and the volume of the reaction vessel are enlarged or reduced according to corresponding proportions as follows ：1H NMR(400MHz,DMSO)δ8.45(s,1H),8.17(s,1H),7.84(dd,J＝8.2,5.5Hz,2H),7.79(s,1H),7.63(d,J＝8.1Hz,2H),7.36(t,J＝8.7Hz,2H),7.01(d,J＝8.0Hz,2H),4.68(q,J＝12.7Hz,2H),4.39(s,2H),2.63(s,3H).; the physicochemical and structural parameters of compound I-b are shown in Table 1.
Example 9: preparation of Compounds I-c:
Under the condition of low-temperature ice bath, 0.1 g of compound I-a-2 and 15ml of anhydrous acetic acid are added into a 100 ml round bottom flask, 10.7 ml of 30% hydrogen peroxide solution in which 2mg of ammonium molybdate is dissolved is slowly added dropwise under stirring, and then the reaction system is moved to room temperature for reaction for 8 hours. After the completion of the reaction, 15ml of water was added and extracted three times with ethyl acetate (15 ml×3), and the organic phase was washed three times with a saturated sodium bisulfate solution (15 ml×3) and a saturated sodium chloride solution (15 ml×3) in this order, and the combined organic layers were dried over anhydrous sodium sulfate; vacuum filtering, concentrating the filtrate to remove solvent, and purifying with dichloromethane/methanol (20:1, volume/volume) eluent column chromatography to obtain compound I-c; yield: 93%. When R 1 is phenyl and R 2 is 4-trifluoromethoxybenzyl, the nuclear magnetic data of the compound I-c-1 is that the prepared amount of the compound I-c-1 and the volume of the reaction vessel are enlarged or reduced according to corresponding proportions as follows ：1H NMR(400MHz,DMSO)δ8.51(s,1H),8.27(s,1H),7.87-7.81(m,3H),7.55(t,J＝7.5Hz,2H),7.46-7.41(m,3H),7.31(d,J＝8.1Hz,2H),5.25(s,2H),4.41(s,2H),2.65(s,3H).; the physicochemical and structural parameters of compounds I-c are shown in Table 1.
Example 10: the antibacterial activity measurement result of the 1,3, 4-oxadiazole psoralen 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, G.z: the gibberella wheat germ has the Latin name: gibberella zeae, P.p: apple ring rot germ, its latin name is: physalospora piricola, P.s: rhizoctonia solani, its Latin name is: pellicularia sasakii, S.s: sclerotinia sclerotiorum, the Latin name of which is: sclerotinia sclerotiorumalis 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 assay are shown in Table 2, and Table 2 shows that all the compounds synthesized in the present invention have different degrees of bactericidal activity at 50. Mu.g/ml. For tomato early blight bacteria, the inhibition rate of the compounds DJY-2-105, DJY-2-160, DJY-2-173, DJY-2-180, DJY-2-192, DJY-2-194, DJY-2-176 and DJY-2-200 of the invention is more than 65%, which is higher than that of the contrast drugs psoralen and YZK-C2210%; for gray mold bacteria of cucumber, the inhibition rate of the compounds DJY-2-160, DJY-2-174, DJY-2-170, DJY-2-178, DJY-2-184, DJY-2-176, DJY-2-199 and DJY-2-200 is more than 75%, the bactericidal activity of the compounds DJY-2-174, DJY-2-170 and DJY-2-176 is more than 95% and the bactericidal activity of the compounds DJY-2-174, DJY-2-170 and DJY-2-176 is more than 2220% higher than that of the control drugs psoralen and YZK-C; for brown spot germ of peanut, the inhibition rate of the compounds DJY-2-106, DJY-2-160, DJY-2-174 and DJY-2-127 is above 70%, which is equal to or higher than that of the control drugs psoralen and YZK-C22, wherein the sterilization activity of the compound DJY-2-160 is highest and is up to 88%, which is higher than that of the control drugs psoralen by above 20%; for the wheat scabies bacteria, the inhibition rate of the compounds DJY-2-105, DJY-2-112, DJY-2-129, DJY-2-160, DJY-2-168, DJY-2-173, DJY-2-174, DJY-2-192 and DJY-2-200 is more than 60 percent, which is equal to or higher than that of the control drugs psoralen and YZK-C22, wherein the inhibition rate of the compounds DJY-2-105, DJY-2-160 and DJY-2-168 is nearly 10 percent higher than that of the control drugs psoralen; for apple ring rot fungi, the inhibition rate of the compounds DJY-2-117, DJY-2-160, DJY-2-169, DJY-2-173, DJY-2-171, DJY-2-174, DJY-2-180 and DJY-2-192 is above 60 percent, which is above 20 percent higher than that of the control drug psoralen; for Rhizoctonia solani, the inhibition rate of the compounds DJY-2-160 and DJY-2-192 is more than 70%, which is more than 20% higher than that of the reference medicine psoralen; for Sclerotinia sclerotiorum, the inhibition rate of the compounds DJY-2-160, DJY-2-174, DJY-2-192 and DJY-2-194 is more than 65%, which is superior to that of the control drugs psoralen and YZK-C22, wherein the inhibition rate of the compounds DJY-2-174, DJY-2-192 and DJY-2-194 is more than 10% higher than that of the control drugs psoralen.
Example 11: the application of the 1,3, 4-oxadiazole psoralen derivative I in preparing pesticide compositions comprises the following steps:
The 1,3, 4-oxadiazole psoralen derivative I of the invention is used for preparing a pesticide composition, and the composition contains the 1,3, 4-oxadiazole psoralen derivative I and an intermediate thereof as active ingredients, wherein the content of the active ingredients is 0.1 to 99.9 percent by weight, 99.9 to 0.1 percent by weight of solid or liquid auxiliary agent and optionally 0 to 50 percent by weight of surfactant.
Example 12: the application of the 1,3, 4-oxadiazole psoralen derivative I in preparing pesticide compound compositions comprises the following steps:
the 1,3, 4-oxadiazole psoralen 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 1,3, 4-oxadiazole psoralen derivative I and the intermediate thereof and other commodity pesticides, namely, insecticides, acaricides, bactericides, antiviral agents or plant activators as active ingredients, and the 1,3, 4-oxadiazole psoralen derivative I and the intermediate thereof and other commodity pesticides, namely, the insecticides, acaricides, bactericides, antiviral agents or plant activators, according to the invention have the mass percentage of 1% -99% -1%, the content of 0.1% -99.9% by weight of solid or liquid auxiliary agents, 99.9% -0.1% by weight of active ingredients and optionally 0% -50% by weight of surfactants.
Example 13: the application of the 1,3, 4-oxadiazole psoralen derivative I and the pesticide combination in the prevention and treatment of agricultural and forestry plant insect pests and gardening plant insect pests:
The 1,3, 4-oxadiazole psoralen derivative I is combined with any one or two of commercial pesticides to form an insecticidal composition for preventing and controlling insect pests of agriculture, forestry and horticultural plants, wherein the commercial pesticides are selected from the group consisting of: bifenthrin, permethrin, ethofenprox, flumethrin, fluramid, imidacloprid nitenpyram, imidaclothiz, thiacloprid, thiamethoxam, clothianidin, dinotefuran, collidine bifenthrin, permethrin, ethofenprox, flumethrin, fluramid, 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, fenoxacarb, fenoxaprop-p-ethyl, pyridalyl, clomazone, clofentezine, propargite, diafenthiuron, pymetrozine, spirodiclofen, spirotetramat, azocyclotin, buprofezin, monosultap, chlorfenapyr, tetrachlorethamide, flufenamid, cyanogen, butene fipronil, tolfenpyrad, chlorfenapyr, pyrazinone, etoxazole, tebufenpyrad, pyridaben, pyrifos, tebufenozide; the mass percentage of the 1,3, 4-oxadiazole psoralen derivative I in the insecticidal composition is 1% -90%, and the mass percentage of the 1,3, 4-oxadiazole psoralen 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 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, white fly, bemisia tabaci, black tail leafhopper, green 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, mealy bugs, sang Dun scale, sagittaria verrucosa, piricosa, meadow wax beetles, korean ball mealy bugs, pear net bugs, banana net bugs, lygus lucorum, small flower bugs, needle-border bugs, rice spider border bugs, brown bugs, rice black bugs, green bugs, alfalfa bugs, medium black bugs, chrysopa, lilaces, chinese chrysopa, moth, clothes moths, yellow thorns, brown moths, flat moths 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 leaf roller 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, 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, chest needle worm, valley bark beetle, black bark beetle, citrus gill worm, jin Yuanji budworm, yellow meal worm, black meal worm, red-yellow larch, hybrid-yellow larch, copper green-yellow larch, dark-black tortoise, giant-black gill-white tortoise, mulberry longhorn, star longhorn, orange-brown longhorn, peach-red longhorn, great ape leaf worm, small ape leaf worm, yellow-head melon, yellow-curved striped flea, green bean image, pea image, broad bean image, corn image, rice image, wheat leaf bee, pear-fruit bee, yellow-banded cornflower, armyworm white star-cornflower, boll fly-hanging cornflower, cotton bollworm tooth-lip cornflower, borer black spot wart, mosquito, fly, horsefly, wheat red-sucking maggot, wheat Huang Xi thick beetle, rice gall midge, citrus fruit fly, melon fruit fly, wheat She Hui fly, american leaf fly, bean stalk black fly, wheat fly, seed fly, onion fly, radish fly, umbrella-skirt, corn borer, myalid 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.
Example 14: the application of the 1,3, 4-oxadiazole psoralen derivative I and the bactericide combination in preventing and controlling plant diseases of agriculture, forestry and gardening is that:
The 1,3, 4-oxadiazole psoralen derivative I is combined with any one or two of commercial bactericides to form a bactericidal composition for preventing and controlling plant diseases of agriculture, forestry and gardening, wherein the commercial bactericides are selected from the group consisting of: benzothiadiazole, tiadinil, thiabendazole, methidathiamide, 4-methyl-1, 2, 3-thiabendazole-5-carboxylic acid, sodium 4-methyl-1, 2, 3-thiabendazole-5-carboxylate, ethyl 4-methyl-1, 2, 3-thiabendazole-5-carboxylate, DL-beta-aminobutyric acid, isothiabendazole, 3, 4-dichloroisothiazole-5-carboxylic acid, sodium 3, 4-dichloroisothiazole-5-carboxylate, ethyl 3, 4-dichloroisothiazole-5-carboxylate, ribavirin, antofen, ningnanmycin or salicylic acid, cymoxanil, thiram, ziram, mancozeb, fosetyl, thiophanate, chlorothalonil, difenoconazole, benomyl, fenpropizine, thiophanate, tolfenpropazine, triflumine, dimethomorph, high-efficiency mebendazole, mechlor, flufenamide, sulfenamide methanesulfonamide, thiabendazole, leaf-carrier, cyclopropylamide, cyflufenamid, cycloxaprid, fenhexamid, silthiopham, carboxin oxide, mefenoxam formamide, metolachlor, flufenamide, furametpyr, thifluzamide, boscalid, penthiopyrad, isopyrazam, bixafen, fluopyram, flupyraclostrobin, flupyrad, flupyraclostrobin, flupirtine formamide, metolachlor, fluoamide, furametpyr, thifluzamide, boscalid, fluxapyroxad, fluzamide, fluxad, flud, penthiopyrad, isopyrazam, bixafen, fluopyram, trifloxystrobin, enestroburin, epoxiconazole, furfuryl azole, cyproconazole, difenoconazole, diniconazole, high-efficiency diniconazole, epoxiconazole, fenbuconazole, fluquinconazole, flusilazole, flutriafol, epoxiconazole, difenoconazole, propiconazole, epoxiconazole, hexaconazole, imibenconazole, ipconazole, metconazole, myclobutanil, penconazole, propiconazole, prothioconazole, simeconazole, tebuconazole, tetraconazole, triadimenol, triticonazole, bitertanol, thiabendazole, epoxiconazole, difenoconazole, tebuconazole, and the like corncob, imazalil, high-efficiency imazalil, prochloraz, triflumizole, cyazofamid, imidazolone, oxaimidazole, fenoxanil, famoxadone, oxadone, oxadixyl, ethaboxam, hymexazol, xin Sai ketone, benthiavalicarb-isopropyl, dode-morpholine, fenpropimorph, tridemorph, fenpiclonil, fludioxonil, fluazinam, pyripyroxim, cyprodinil, fluoxastrobin, cyprodinil fluoxastrobin, azoxystrobin, cyprodinil, pyrimethanil, chloropyrimol, flubenyrimol, fenamidone, dithianon, ethoxyquinoline, hydroxyquinoline, propiquin, phenoxyquinoline, diethofencarb, iprovalicarb, benthiavalicarb, propamocarb, sulfencarb, diphenfos, iprobenfos, pyrifos, tolclofos-methyl, blasticidin, kasugamycin, polyoxin, validamycin, streptomycin, metalaxyl, furalaxyl, benalaxyl, furalaxyl, carbendazim, benomyl, thiophanate-methyl, triazolone, bupirimate, dimethirimol, ethirimol, captan, folpet, ethephon, fluclomazone, dimethachlor, chlorothalonil, isoprothiolane, metconazole, pentachloronitrobenzene, propineb, triclophate, aluminum, sulphur, copper sulphate, copper chloride solution, chlorpyrifos, cuprous oxide, copper hydroxide, metrafenone, pencycuron, pyridazinone, tetrachlorophthalide, fluquindox, spiroxamine, tricyclazole, zinyl, dodine, guanamine, chlornitramine, bensulfenamide, indolyl ester, sodium disultone, quinocetone, probenazole, bronitol, methyl iodide, carb, diline ester, dazomet, diisopropyl ether, fosthiazate, fenitrothion, triazophos, carbosulfan, triadimefon, sulfuryl fluoride, dichloropropene, dichloroisonicotinic acid, and allylisothiazole; the total mass percentage of the 1,3, 4-oxadiazole psoralen derivative I in the sterilization composition is 1% -90%, and the weight percentage of the 1,3, 4-oxadiazole psoralen derivative I and the commercial sterilization agent 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; 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.
Example 15: the application of the 1,3, 4-oxadiazole psoralen derivative I and the anti-plant virus agent in preventing and controlling the virus diseases of agriculture and forestry and gardening plants:
The 1,3, 4-oxadiazole psoralen derivative I is combined with any one or two of commercial antiviral agents to form an antiviral composition for preventing and treating viral diseases of agricultural, forestry and horticultural plants, wherein the commercial antiviral agents are selected from the group consisting of: benzothiadiazole, tiadinil, isotiadinil, 4-methyl-1, 2, 3-thiadiazole-5-carboxylic acid, sodium 4-methyl-1, 2, 3-thiadiazole-5-carboxylate, ethyl 4-methyl-1, 2, 3-thiadiazole-5-carboxylate, 3, 4-dichloroisothiazole-5-carboxylic acid, sodium 3, 4-dichloroisothiazole-5-carboxylate, ethyl 3, 4-dichloroisothiazole-5-carboxylate, DL-beta-aminobutyric acid, ribavirin, antofine, ningnanmycin, thiamide, mefenamide or salicylic acid, pyrimidomycin, dichloroisonicotinic acid, allylisothiazole, validoxylamine, validamycin, moroxydine hydrochloride; the total mass percentage of the 1,3, 4-oxadiazole psoralen derivatives I in the antiviral composition is 1% -90%, and the mass percentage of the 1,3, 4-oxadiazole psoralen derivatives 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 16: the application of the 1,3, 4-oxadiazole psoralen derivative I and acaricide combination in controlling agricultural and forestry and horticultural plant acarid is that:
Any one or two of the 1,3, 4-oxadiazole psoralen derivatives I and commercial acaricides are combined to form the acaricide composition which is used for preventing and controlling mites of agricultural, forestry and horticultural plants, and the commercial acaricide is selected from the following: dichlorvos, heptylphosphines, acephate, dibromophosphorus, pyrimidine phosphorus, chlormethiphos, ethion, chlorfenphos, vos methyl pyrifos, quetiapine, aphid, amifos, chlorimfos, iminofos, flumethrin, bifenthrin cyhalothrin, lambda-cyhalothrin, fenpropathrin, flumetofen, fenhexamid, fenfluramine, bifenthrin, benfuracarb, carbofuran, fenoxacarb, benomyl, clomazone, ding Liusu methomyl, fenbucarb, fenbucin 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 1,3, 4-oxadiazole psoralen derivatives I in the acaricidal composition is 1% -90%, and the mass percentage of the 1,3, 4-oxadiazole psoralen derivatives 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 1,3, 4-oxadiazole psoralen 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.
TABLE 2 bacteriostatic Activity of 1,3, 4-oxadiazole psoralen derivatives I (inhibition rate 50. Mu.g/ml/%)
Sequence number Compounds of formula (I) A.s B.c C.a G.z P.p P.s S.s
1 DJY-2-103 64 45 30 39 32 17 44
2 DJY-2-104 60 31 28 48 21 21 37
3 DJY-2-105 78 42 17 75 15 28 33
4 DJY-2-106 63 29 72 29 5 36 61
5 DJY-2-107 57 40 24 52 38 24 24
6 DJY-2-109 64 39 14 52 21 21 35
7 DJY-2-111 63 47 37 45 38 15 43
8 DJY-2-112 58 49 31 70 25 25 57
9 DJY-2-114 56 58 47 40 43 21 60
10 DJY-2-115 44 55 21 49 19 13 45
11 DJY-2-117 47 42 48 46 76 17 35
12 DJY-2-123 34 34 29 56 28 18 46
13 DJY-2-121 59 50 38 24 24 9 52
14 DJY-2-129 43 47 38 61 12 11 55
15 DJY-2-120 65 41 21 29 32 26 47
16 DJY-2-116 38 73 19 34 11 22 39
17 DJY-2-108 57 43 35 25 26 24 53
18 DJY-2-160 89 85 88 73 77 77 65
19 DJY-2-168 65 58 59 72 53 38 55
20 DJY-2-169 63 42 64 52 63 53 59
21 DJY-2-173 75 49 63 67 75 23 62
22 DJY-2-171 66 45 60 51 72 27 57
23 DJY-2-174 60 99 72 61 64 43 70
24 DJY-2-170 64 100 62 53 58 36 61
25 DJY-2-178 50 88 62 40 31 28 48
26 DJY-2-180 72 44 59 34 65 38 56
27 DJY-2-179 35 36 56 46 43 21 25
28 DJY-2-181 37 48 55 39 38 23 53
29 DJY-2-192 70 66 46 67 70 74 76
30 DJY-2-197 64 53 61 48 59 24 59
31 DJY-2-194 75 61 59 52 58 23 73
32 DJY-2-184 61 87 64 56 61 26 37
33 DJY-2-176 72 99 63 52 53 25 54
34 DJY-2-199 37 57 32 50 38 31 22
35 DJY-2-200 79 84 61 62 61 48 42
36 DJY-2-127 65 34 74 58 62 59 32
37 Psoralen 56 50 65 63 44 52 58
38 YZK-C22 58 72 74 75 57 81 61
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, G.z: the gibberella wheat germ has the Latin name: gibberella zeae, P.p: apple ring rot germ, its latin name is: physalospora piricola, P.s: rhizoctonia solani, its Latin name is: pellicularia sasakii, S.s: sclerotinia sclerotiorum, the Latin name of which is: sclerotinia sclerotiorumalis.

Claims (5)

1. The 1,3, 4-oxadiazole psoralen derivatives are characterized by containing 1,3, 4-oxadiazole and psoralen structures at the same time, and have a structural general formula shown in a formula I:
Wherein R 1 is selected from: hydrogen, 4-fluoro; r 2 is selected from 3-methylbenzyl, allyl, (E) -2- (2-methoxy-1- (methoxyimino) -2-oxoethyl) benzyl, (E) -2- (1, 3-dimethoxy-3-oxoprop-1-en-2-yl) benzyl, 3-methylbut-2-enyl, benzoylmethyl, 4-trifluoromethoxybenzyl, 2- (4-chlorophenyl) ethyl.
2. The specific synthetic route and method of the 1,3, 4-oxadiazole psoralen derivatives according to claim 1 are as follows:
the definition of the substituent is as follows,
R 1 is selected from: hydrogen, 4-fluoro; r 2 is selected from 3-methylbenzyl, allyl, (E) -2- (2-methoxy-1- (methoxyimino) -2-oxoethyl) benzyl, (E) -2- (1, 3-dimethoxy-3-oxoprop-1-en-2-yl) benzyl, 3-methylbut-2-enyl, benzoylmethyl, 4-trifluoromethoxybenzyl, 2- (4-chlorophenyl) ethyl;
the specific synthesis method comprises the following steps:
A. preparation of compound 3:
Adding the compound 1 into a reaction bottle, adding the compound 2, then slowly dropwise adding 98% concentrated sulfuric acid under stirring, and stirring at room temperature; after the reaction is finished, adding a proper amount of methanol, then pouring the methanol into ice water to generate a large amount of white solid, and carrying out suction filtration and drying to obtain a compound 3;
B. Preparation of compound 5:
Taking a compound 3, adding a proper amount of anhydrous acetonitrile into a reaction bottle, then sequentially adding potassium carbonate, potassium iodide and a compound 4 under stirring, and heating and refluxing; after the reaction is finished, removing most acetonitrile under reduced pressure, adding water and ethyl acetate for extraction, washing an organic phase with saturated sodium chloride solution, drying with anhydrous sodium sulfate, carrying out vacuum filtration, concentrating filtrate to remove solvent, and purifying by column chromatography to obtain a compound 5;
C. preparation of Compound 6:
Adding a proper amount of isopropanol into a reaction bottle, slowly dropwise adding 1 mol/L sodium hydroxide solution under stirring, and heating for reflux; after the reaction is finished, removing most of isopropanol under reduced pressure, regulating the pH value of a system to be 1-2 by using 1 mol/L hydrochloric acid solution, and carrying out suction filtration and drying on the generated solid to obtain a compound 6;
D. preparation of compound 7:
Taking a compound 6, adding a proper amount of absolute methanol into a reaction bottle, then slowly dropwise adding 98% concentrated sulfuric acid under stirring, and heating and refluxing; after the reaction is finished, removing most of methanol under reduced pressure, adding water and ethyl acetate into residues for extraction, washing an organic phase with saturated sodium chloride solution, drying with anhydrous sodium sulfate, carrying out vacuum filtration, concentrating filtrate to remove solvent, and purifying by column chromatography to obtain a compound 7;
E. preparation of Compound 8:
Taking a compound 7, adding a proper amount of methanol into a reaction bottle, slowly dropwise adding 80% hydrazine hydrate under stirring, and heating and refluxing; after the reaction is finished, removing most of methanol under reduced pressure, adding water and ethyl acetate into residues for extraction, washing an organic phase with saturated sodium chloride solution, drying with anhydrous sodium sulfate, carrying out reduced pressure suction filtration, concentrating filtrate to remove solvent, and purifying by column chromatography to obtain a compound 8;
F. Preparation of Compound 9:
Adding a proper amount of absolute ethyl alcohol into a reaction bottle, adding potassium hydroxide under stirring, slowly dripping carbon disulfide, and heating for reflux; after the reaction is finished, removing most of ethanol under reduced pressure, adding 1mol/L hydrochloric acid solution into residues to adjust the pH value of a system to be 1-2, extracting ethyl acetate, washing an organic phase with saturated sodium chloride solution, drying with anhydrous sodium sulfate, carrying out vacuum filtration, concentrating filtrate to remove a solvent, and purifying by column chromatography to obtain a compound 9;
G. preparation of Compound I-a:
Adding a proper amount of N, N-dimethylformamide into a reaction bottle, sequentially adding potassium hydroxide, R 2 -Cl or R 2 -Br, and stirring at room temperature; after the reaction is finished, adding a proper amount of water and ethyl acetate for extraction, washing an organic phase with a saturated sodium chloride solution, drying with anhydrous sodium sulfate, carrying out vacuum filtration, concentrating filtrate to remove a solvent, and purifying by column chromatography to obtain the compound I-a;
H. Preparation of Compound I-b:
Under the low-temperature ice bath condition, taking a compound I-a, adding a proper amount of dichloromethane into a reaction bottle, then slowly dropwise adding a dichloromethane solution in which m-chloroperoxybenzoic acid is dissolved, and moving the system to room temperature for stirring; after the reaction is finished, removing most of dichloromethane under reduced pressure, adding a proper amount of ethyl acetate into residues, washing with 0.25 mol/L disodium hydrogen phosphate solution and saturated sodium chloride solution in sequence, drying with anhydrous sodium sulfate, carrying out vacuum filtration, concentrating filtrate to remove solvent, and purifying by column chromatography to obtain a compound I-b;
I. Preparation of Compounds I-c:
Under the low-temperature ice bath condition, taking a compound I-a, adding a proper amount of acetic acid into a reaction bottle, slowly dropwise adding a hydrogen peroxide solution in which ammonium molybdate is dissolved under stirring, and then moving the system to room temperature for stirring; after the reaction, water and ethyl acetate are added for extraction, the organic phase is washed by saturated sodium bisulfate solution and saturated sodium chloride solution in sequence, dried by anhydrous sodium sulfate, filtered under reduced pressure, the filtrate is concentrated to remove the solvent, and the compound I-c is obtained by column chromatography purification.
3. Use of the 1,3, 4-oxadiazole psoralen derivatives of claim 1 in the preparation of an agricultural fungicide; the fungi controlled by the agricultural fungicide are selected from: alternaria solani, botrytis cinerea, brown spot of peanut, alternaria wheat, rhizoctonia cerealis, rhizoctonia solani, and Sclerotinia oleander.
4. An agricultural bactericidal composition comprising the 1,3, 4-oxadiazole psoralen derivative according to claim 1 as an active ingredient; the composition comprises from 0.1% to 99.9% by weight of active ingredient, from 99.9% to 0.1% by weight of solid or liquid adjuvant, and optionally from 0 to 25% by weight of surfactant.
5. An agricultural bactericidal compound composition comprising the 1,3, 4-oxadiazole psoralen derivative of claim 1 and other commercial bactericides as active ingredients; the ratio of the 1,3, 4-oxadiazole psoralen derivatives to other commercial bactericides is 1 percent to 99 percent to 1 percent by mass, and the compound composition comprises 1 percent to 99 percent by weight of active ingredients and 99 percent to 1 percent by weight of solid or liquid auxiliary agents.
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Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN1566114A (en) * 2003-06-16 2005-01-19 高和英 Novel psoralen derivative for annihilating live virus or germ

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US8071642B2 (en) * 2007-06-28 2011-12-06 Rutgers, The State University Of New Jersey Dimethyl amino ethyl ether psoralens and methods for their production and use

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* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN1566114A (en) * 2003-06-16 2005-01-19 高和英 Novel psoralen derivative for annihilating live virus or germ

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* Cited by examiner, † Cited by third party
Title
Design, synthesis and docking studies of new furobenzopyranones and pyranobenzopyranones as photoreagent towards DNA and as antimicrobial agents;Farag, Nahla A. H. 等;European Journal of Medicinal Chemistry;第45卷(第01期);第317-325页 *

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