CN112480022A

CN112480022A - 3, 4-dichloroisothiazole-beta-keto acid ester derivatives, and preparation method and application thereof

Info

Publication number: CN112480022A
Application number: CN202110006446.5A
Authority: CN
Inventors: 范志金; 吕游; 王炜博; 李坤; 张越; 陈蕾; 郝泽生; 张乃楼; 刘笑宇; 高卫
Original assignee: Nankai University
Current assignee: Nankai University
Priority date: 2021-01-05
Filing date: 2021-01-05
Publication date: 2021-03-12

Abstract

The invention provides 5- (3, 4-dichloroisothiazole) -beta-ketonic acid ester derivatives, a preparation method and application thereof, and particularly relates to the 5- (3, 4-dichloroisothiazole) -beta-ketonic acid ester derivatives, wherein the chemical structure general formula of the derivatives is shown as formula I: i:

Description

3, 4-dichloroisothiazole-beta-keto acid ester derivatives, and preparation method and application thereof

Technical Field

The technical scheme of the invention relates to an isothiazole beta-ketoacid ester derivative, in particular to a 3, 4-dichloroisothiazole-beta-ketoacid ester derivative, and specifically to a 5- (3, 4-dichloroisothiazole) -beta-ketoacid ester derivative.

Background

The heterocyclic compound is an important source for the structure development of pesticides, and is a common high-efficiency, low-toxicity and broad-spectrum bioactive lead compound. Most of active molecules reported in the literature have heterocyclic structures. In the related pesticide patents, N-containing heterocycles (pyridine, pyrazole, pyrimidine and the like), sulfur-containing heterocycles, thiazole, fused heterocycles and the like account for more than half of the total number, but N-and S-containing compounds (including thiazole, isothiazole, thiadiazole and the like) often have wide biological activity. Most of the bioactive compounds reported in the patent literature have heterocyclic structures; five-membered heterocyclic compounds are reported in the literature to have activity as plant activators, fungicides, plant growth regulators and insecticides (Chendan Nu et al, modern pesticides, 2014, 14 (2): 5-10.).

The beta-keto ester compound is a special molecular skeleton with both nucleophilic and electrophilic functional groups, the beta-ketocarbonyl group has strong electron withdrawing property, and can further strengthen the acidity of sigma-H to make the whole molecule produce enol tautomerism, and because of enol isomerism, a conjugated structure exists between hydrogen bond and carbon-carbon double bond in the molecule, which further strengthens the stability of enol form and also strengthens the reactivity of enol form as nucleophilic reagent. The beta-keto acid ester compound can continuously perform enol tautomerism in an acidic or basic environment and can be combined with various metal chelates, so that the beta-keto acid ester compound can perform various reactions, can construct carbon-carbon bonds, carbon-heteroatom bonds or carbon-halogen bonds, and can be further converted into various more valuable intermediates, such as various heterocycles like coumarin, pyrimidine rings, pyrazole rings, oxazole rings and the like, and provides a complex core skeleton for the intermediates (Govender, T.et al.chemical reviews 2016, 116 (16): 9375-.

In order to search and discover pesticide lead and candidate compounds with higher efficiency, broad spectrum, low toxicity, low ecological risk and no cross resistance, the invention combines the 3, 4-dichloroisothiazole heterocycle and the beta-ketonic acid ester structure, designs and synthesizes a class of 3, 4-dichloroisothiazole-beta-ketonic acid ester 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 a novel 3, 4-dichloroisothiazole-beta-keto acid ester derivative, provides a method for regulating and controlling the biological activity of agricultural, horticultural and sanitary plant pests and plant pathogens by using the compound and a determination method thereof, and simultaneously provides application of the compound 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 5- (3, 4-dichloroisothiazole) -beta-ketonic acid ester compound with insecticidal, acaricidal, bactericidal and plant virus resistant activities in the agricultural field, the horticultural field and the forestry field and used for inducing plants to generate disease resistant activities is shown as I:

I：

wherein R is¹Selected from: hydrogen, methyl, ethyl, fluorine, chlorine; r²Selected from: methyl, ethyl, alkyl.

The synthetic route of the 3, 4-dichloroisothiazole-beta-keto acid ester derivative I is as follows:

The synthesis of compounds I-1 to I-3 in the above synthetic route can be divided into two conditions, condition A and condition B, according to the reaction conditions.

Wherein R is¹Selected from: hydrogen, methyl, ethyl; r²Selected from: methyl, ethyl, alkyl.

The other synthetic route of the 3, 4-dichloroisothiazole-beta-keto acid ester derivative I is as follows:

wherein R is¹Selected from: hydrogen, fluorine; r²Selected from: methyl, ethyl, alkyl.

The invention also discloses a synthesis route of the 3, 4-dichloroisothiazole-beta-keto acid ester derivative I-1, which comprises the following steps:

wherein R is²Selected from: methyl, ethyl, alkyl.

The 3, 4-dichloroisothiazole-beta-keto acid ester derivative I-1 can be prepared by the following synthetic route:

wherein R is²Selected from: methyl, ethyl, alkyl.

The synthesis of compound I-1 in the above route can be classified into two conditions, condition C and condition D, depending on the reaction conditions.

Wherein R is²Selected from: methyl, ethylAn alkyl group.

The synthesis method of the 3, 4-dichloroisothiazole-beta-keto acid ester derivative I comprises the following steps:

synthesizing a 3, 4-dichloroisothiazole-beta-keto acid ester derivative I:

route one condition a:

dissolving compound II (5.0 g, 27.9 mmol) and zinc powder (4.56 g, 69.8 mmol) in 100 ml of dry tetrahydrofuran, adding methanesulfonic acid (135 mg, 1.4 mmol) at room temperature, refluxing the reaction solution for 15 minutes under nitrogen protection, slowly adding dropwise substituted ethyl bromoacetate (55.9 mmol), and after the addition is completed, continuing the reflux reaction for 1-3 hours. Monitoring the reaction by thin-layer chromatography, cooling to room temperature after the reaction is finished, filtering, dripping 30 ml of 3 mol/L hydrochloric acid at room temperature, stirring for 1 hour at room temperature, monitoring the reaction by thin-layer chromatography, and finishing the reaction. The layers were separated by settling, the aqueous phase was extracted with ethyl acetate (3X 30 ml), the organic phases were combined, the organic phase was washed with saturated sodium chloride solution and dried by adding anhydrous sodium sulfate. Vacuum filtering, concentrating, and performing column chromatography (V)_{Petroleum ether}∶V_{Ethyl acetate}And (2) purifying at a ratio of 20: 1-10: 1) to obtain a target product I. The amount of the compound can be enlarged or reduced according to the corresponding proportion, the material ratio II to the substituted alkyl bromoacetate is selected from any proportion between 1: 1 and 1: 5, the reaction time is selected from any time between 1 hour and 20 hours, the material ratio II to the zinc powder is selected from any proportion between 1: 1 and 1: 5, and the material ratio II to the methanesulfonic acid is selected from any proportion between 100: 1 and 10: 1.

Route one condition B:

dissolving a compound II (5.0 g, 27.9 mmol) and zinc powder (4.56 g, 69.8 mmol) in 100 ml of dry tetrahydrofuran, adding cuprous bromide (200 mg, 1.4 mmol) and iodine (355 mg, 1.4 mmol) at room temperature under the protection of argon gas until the color of the reaction solution fades, refluxing the reaction solution for 15 minutes, slowly dropwise adding substituted bromoacetic acid alkyl ester (55.9 mmol), and continuing to reflux and react for 1-3 hours after the dropwise addition is finished. Monitoring the reaction by thin-layer chromatography, cooling to room temperature after the reaction is finished, filtering, and dripping 3 mol/L salt at room temperatureAcid 30 ml and then stirred at room temperature for 1 hour, and the reaction was monitored by thin layer chromatography until the reaction was complete. The layers were separated by settling, the aqueous phase was extracted with ethyl acetate (3X 30 ml), the organic phases were combined, the organic phase was washed with saturated sodium chloride solution and dried by adding anhydrous sodium sulfate. Vacuum filtering, concentrating, and performing column chromatography (V)_{Petroleum ether}∶V_{Ethyl acetate}And (2) purifying at a ratio of 20: 1-10: 1) to obtain a target product I. The amount of the compound can be enlarged or reduced according to the corresponding proportion, the material ratio II to the substituted alkyl bromoacetate is selected from any proportion between 1: 1 and 1: 5, the reaction time is selected from any time between 1 hour and 20 hours, the material ratio II to the zinc powder is selected from any proportion between 1: 1 and 1: 5, and the material ratio II to the brominated imino ketone is selected from any proportion between 100: 1 and 10: 1.

Route one 3, 4-dichloroisothiazole-beta-keto acid ester derivative I-4 synthesis:

compound I-1(18.7 mmol) was dissolved in dry dichloromethane, and sulfonyl chloride (7.55 g, 56.0 mmol) was added dropwise at room temperature, after completion of the addition, at room temperature for 3 hours, followed by heating under reflux for 3 hours. After the thin layer chromatography detection reaction is finished, the reaction solution is concentrated and subjected to column chromatography (V)_{Petroleum ether}∶V_{Ethyl acetate}And (2) purifying at a ratio of 20: 1-10: 1) to obtain the target product I-4. The dosage of the compound can be enlarged or reduced according to the corresponding proportion, the range of the material ratio I-1: sulfonyl chloride is selected from any proportion between 1: 1 and 1: 5, and the reaction time is selected from any time between 1 hour and 20 hours.

Route one 3, 4-dichloroisothiazole-beta-keto acid ester derivative I-5:

compound I-1(18.7 mmol) is dissolved in dry acetonitrile and 1-chloromethyl-4-fluoro-1, 4-diazabicyclo [2.2.2 ] is added at room temperature]Octane bis (tetrafluoroborate) salt (19.64 mmol) was reacted under reflux for 3 hours. After the thin layer chromatography detection reaction is finished, the reaction solution is concentrated and subjected to column chromatography (V)_{Petroleum ether}∶V_{Ethyl acetate}And (2) purifying at a ratio of 20: 1-10: 1) to obtain the target product I-5. The dosage of the compound can be enlarged or reduced according to the corresponding proportion, and the material ratio is I-1: 1-chloromethyl-4-fluorine-1, 4-diazabicyclo [2.2.2]OctaneThe range of bis (tetrafluoroborate) salt is selected from any ratio between 1: 1 and 1: 5, and the reaction time is selected from any time between 1 hour and 20 hours.

The synthesis of the bis 3, 4-dichloroisothiazole-beta-ketonic acid ester derivative I comprises the following steps:

compound IV (50.8 mmol) and anhydrous magnesium chloride (8.8 g, 92.4 mmol) were dispersed in dry tetrahydrofuran, triethylamine (9.35 g, 92.4 mmol) was slowly added dropwise to the reaction flask under ice-bath conditions, after completion of the addition, reaction was carried out at room temperature for 2 hours, then compound III (10.0 g, 46.2 mmol) was slowly added dropwise to the reaction flask under ice-bath conditions, and after completion of the addition, reaction was carried out at room temperature overnight, and PH was adjusted to 1 with 3 mol/l hydrochloric acid, and reaction was carried out at room temperature for 1 hour. After the reaction is finished; the mixture was allowed to stand for separation, the aqueous phase was extracted with ethyl acetate (3X 30 ml), the organic phases were combined, and the organic phase was washed successively with a saturated sodium bicarbonate solution, water and a saturated saline solution, and dried with anhydrous sodium sulfate. And carrying out suction filtration and concentration to obtain a target product I. The amount of the compound can be enlarged or reduced according to the corresponding proportion, the range of the material ratio III to IV is selected from any proportion between 1: 2 and 2: 1, the reaction time is selected from any time between 1 hour and 20 hours, and the range of the material ratio III to the addition amount of the magnesium chloride is selected from any proportion between 1: 1 and 1: 2.

The synthesis of the 3, 4-dichloroisothiazole-beta-ketonic acid ester derivative I-1 comprises the following steps:

meldrum's acid (1.44 g, 10 mmol) was dissolved in dichloromethane, argon was used as a shield, and after adding a base (20 mmol) in an ice-water bath and stirring for 15 minutes, Compound III (2.17 g, 10 mmol) was added dropwise to the reaction mixture, and after 1.5 hours at 0 ℃, the reaction was continued at room temperature for 3.0 hours. After the reaction is finished; acidification with 3 mol/l hydrochloric acid, standing for layering, extraction of the aqueous phase with dichloromethane (3X 30 ml), combination of the organic phases, washing of the organic phase with water, saturated brine in succession, drying with anhydrous sodium sulfate. Filtering, concentrating, and performing column chromatography (V)_{Methylene dichloride}∶V_MethanolAnd (2) purifying at a ratio of 20: 1-10: 1) to obtain an intermediate V. The dosage of the compound can be enlarged or reduced according to the corresponding proportion, and the material ratio III is selected according to the range of the Meldrum's acidFrom 1: 5 to 5: 1, the reaction time is chosen from any time between 1 hour and 20 hours, and the feed ratio III: base is chosen from any ratio between 1: 5 and 5: 1.

And (3) dissolving the intermediate V (10 mmol) with alkyl alcohol, heating, refluxing and reacting overnight, and after the reaction is finished, concentrating the reaction solution to dryness to obtain the target compound I-1.

The synthesis of the tetra 3, 4-dichloroisothiazole-beta-ketonic acid ester derivative I-1 comprises the following steps:

route four condition C:

adding magnesium strips (292 mg, 12 mmol) and iodine simple substances (38 mg, 0.12 mmol) into a 100 ml three-neck flask, dissolving the magnesium strips and the iodine simple substances by using carbon tetrachloride, adding a little ethanol, adding a toluene solution of dialkyl malonate (12 mmol) after the reaction is stable, reacting at room temperature, distilling under reduced pressure to evaporate the solvent after the magnesium strips completely disappear, carrying the solvent by using toluene once, adding toluene as the solvent, dropwise adding a compound III (2.17 g, 10 mmol), and reacting at room temperature overnight; after the reaction is finished; acidification with 3 mol/l hydrochloric acid, standing for layering, extraction of the aqueous phase with ethyl acetate (3X 30 ml), combination of the organic phases, washing of the organic phase with water, saturated brine successively, addition of anhydrous sodium sulfate and drying. Filtering, concentrating, and performing column chromatography (V)_{Methylene dichloride}∶V_MethanolAnd (2) purifying at a ratio of 20: 1-10: 1) to obtain an intermediate VI. The dosage of the compound can be enlarged or reduced according to the corresponding proportion, the material ratio III to the dialkyl malonate is selected from any proportion between 1: 5 and 5: 1, the reaction time is selected from any time between 1 hour and 20 hours, and the material ratio III to the magnesium to the iodine is selected from any proportion between 1: 5 and 100: 1.

Route four condition D:

dialkyl malonate (50.8 mmol) and anhydrous magnesium chloride (8.8 g, 92.4 mmol) were dispersed in dry tetrahydrofuran, triethylamine (9.35 g, 92.4 mmol) was slowly dropped into the reaction flask under ice-bath conditions, after the dropping, the reaction was carried out at room temperature for 2 hours, then compound III (10.0 g, 46.2 mmol) was slowly dropped into the reaction flask under ice-bath conditions,after the addition, the reaction was allowed to proceed overnight at room temperature, and the reaction was carried out at room temperature for 1 hour with 3 mol/l hydrochloric acid at pH 1. After the reaction is finished; the mixture was allowed to stand for separation, the aqueous phase was extracted with ethyl acetate (3X 30 ml), and the organic phases were combined, washed successively with water and saturated brine, and dried over anhydrous sodium sulfate. Filtering, concentrating, and performing column chromatography (V)_{Methylene dichloride}∶V_MethanolAnd (2) purifying at a ratio of 20: 1-10: 1) to obtain an intermediate VI. The dosage of the compound can be enlarged or reduced according to the corresponding proportion, the range of the material ratio III to the dialkyl malonate is selected from any proportion between 1: 5 and 5: 1, the reaction time is selected from any time between 1 hour and 20 hours, the range of the material ratio III to the magnesium chloride is selected from any proportion between 1: 5 and 5: 1, and the range of the material ratio III to the triethylamine is selected from any proportion between 1: 5 and 5: 1.

Dissolving the intermediate VI (10 mmol) with alkyl alcohol, adding strong acid (hydrochloric acid, sulfuric acid and the like) as a catalyst, heating, refluxing and reacting overnight, and concentrating the reaction solution to dryness after the reaction is finished to obtain the target compound I-1.

The invention provides application of the 3, 4-dichloroisothiazole-beta-keto acid ester derivative I in preparation of a fungicide.

The invention provides application of the 3, 4-dichloroisothiazole-beta-keto acid ester derivative I in preparation of a tobacco mosaic virus resistant agent.

The invention provides application of the 3, 4-dichloroisothiazole-beta-keto acid ester derivative I in preparation of a plant activator for inducing tobacco to resist tobacco mosaic virus.

The invention provides application of the 3, 4-dichloroisothiazole-beta-keto acid ester derivative I in prevention and treatment of agricultural and forestry and horticultural plant insect pests.

The 3, 4-dichloroisothiazole-beta-keto acid ester derivative I is applied together with agricultural chemicals; the agrochemical is selected from: one or more of insecticide, bactericide, plant virus resisting agent and acaricide.

The 3, 4-dichloroisothiazole-beta-keto acid ester derivative I and any one or two of the insecticides are combined to form an insecticidal composition for preventing and treating agricultural and forestry and horticultural plant insect pests;

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 3, 4-dichloroisothiazole-beta-ketonic acid ester derivative I in the insecticidal composition is 1-90%; preferably, the mass percentage of the 3, 4-dichloroisothiazole-beta-ketonic acid ester derivative I to the pesticide 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.

The 3, 4-dichloroisothiazole-beta-keto acid ester derivative I and any one or two of the bactericides are combined to form a bactericidal composition for preventing and treating agricultural and forestry and horticultural plant diseases;

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, zoxamide, ethirimide, iprodione, azoxystrobin, dimoxystrobin, fluoxastrobin, kresoxim-methyl, metominostrobin, picoxystrobin, pyraclostrobin, trifloxystrobin, enestroburin, alkene oxime amine, epoxiconazole, bromuconazole, cyproconazole, difenoconazole, diniconazole, tebuconazole, fenbuconazole, fluquinconazole, flusilazole, flutriafol, hexaconazole, imibenconazole, ipconazole, metconazole, myclobutanil, penconazole, propiconazole, prothioconazole, simeconazole, tebuconazole, tetraconazole, triadimenol, triticonazole, bitertanol, thiabendazole, imazalil, prochloraz, cyazofamid, pyraclostrobin, 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 3, 4-dichloroisothiazole-beta-ketonic acid ester derivative I accounts for 1-90% of the total mass of the sterilization composition; the ratio of the 3, 4-dichloroisothiazole-beta-ketonic acid ester 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 3, 4-dichloroisothiazole-beta-ketonic acid ester derivative I 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 3, 4-dichloroisothiazole-beta-ketonic acid ester derivative I accounts for 1-90% of the antiviral composition in percentage by mass; preferably, the ratio of the 3, 4-dichloroisothiazole-beta-ketonic acid ester derivative I to the anti-plant virus agent is 1 to 99 to 1 percent by mass percent;

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 3, 4-dichloroisothiazole-beta-ketonic acid ester derivative I 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 3, 4-dichloroisothiazole-beta-ketonic acid ester derivative I accounts for 1-90% of the acaricidal composition in total mass percentage; the ratio of the 3, 4-dichloroisothiazole-beta-ketonic acid ester 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 3, 4-dichloroisothiazole-beta-keto acid ester derivative I is determined as follows:

the bactericidal activity of the 3, 4-dichloroisothiazole-beta-keto acid ester derivative I is determined as follows:

the bactericidal or bacteriostatic activity of the 3, 4-dichloroisothiazole-beta-ketonic acid ester derivative I adopts 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, PP: apple ring rot, its latin name is: physiosporia piricola, RS: rhizoctonia solani with the latin name: rhizoctonia solani, SS: sclerotinia sclerotiorum, its latin name is: sclerotina sclerotiorum.

The invention has the beneficial effects that: the 3, 4-dichloroisothiazole-beta-ketonic acid ester derivative I is subjected to lead optimization, and the 3, 4-dichloroisothiazole-beta-ketonic acid ester derivative I is screened for antibacterial activity.

The synthesis, biological activity and application of the 3, 4-dichloroisothiazole-beta-keto acid ester derivative I are more specifically illustrated by specific preparation and biological activity measurement examples, which are only used for specifically illustrating the invention and not limiting the invention, and particularly, the biological activity is only illustrated and not limiting the patent, and the specific embodiments are as follows:

example 1: preparation of Compound ly-1-11:

dissolving compound II (5.0 g, 27.9 mmol) and zinc powder (4.56 g, 69.8 mmol) in 100 ml of dry tetrahydrofuran, adding methanesulfonic acid (135 mg, 1.4 mmol) at room temperature, refluxing the reaction solution for 15 minutes under nitrogen protection, slowly adding ethyl bromoacetate (9.33 g, 55.9 mmol) dropwise, and after the addition is completed, continuing the reflux reaction for 1-3 hours. Monitoring the reaction by thin-layer chromatography, cooling to room temperature after the reaction is finished, filtering, dripping 30 ml of 3 mol/L hydrochloric acid at room temperature, stirring for 1 hour at room temperature, monitoring the reaction by thin-layer chromatography, and finishing the reaction. The layers were separated by settling, the aqueous phase was extracted with ethyl acetate (3X 30 ml), the organic phases were combined, the organic phase was washed with saturated sodium chloride solution and dried by adding anhydrous sodium sulfate. Vacuum filtering, concentrating, and performing column chromatography (V)_{Petroleum ether}∶V_{Ethyl acetate}20: 1-10: 1) to obtain a target product ly-1-11; the yield is 68 percent; the nuclear magnetic data are as follows:¹H NMR(400MHz，CDCl₃) δ 12.46(s, 1H), 6.15(s, 1H), 4.29(q, J ═ 7.2Hz, 2H), 1.35(t, J ═ 7.1Hz, 3H). The amount of the compound ly-1-11 to be prepared and the volume of the reaction vessel are enlarged or reduced in a corresponding ratio.

Example 2: preparation of Compound ly-1-25:

compound ly-1-11(5.0 g, 18.7 mmol) was dissolved in dry dichloromethane, and sulfonyl chloride (7.55 g, 56.0 mmol) was added dropwise at room temperature, and after completion of the addition, the reaction was carried out at room temperature for 3 hours, followed by heating under reflux for 3 hours. After TLC detection reaction, the reaction solution is concentrated and subjected to column chromatography (V)_{Petroleum ether}∶V_{Ethyl acetate}And (20: 1) to 10: 1) purifying to obtain the target product ly-1-25. (ii) a The yield is 98 percent; the nuclear magnetic data are as follows:¹H NMR(400MHz，CDCl₃)δ12.67(s，1H) 4.40(q, J ═ 7.1Hz, 2H), 1.41(t, J ═ 7.1Hz, 3H). The amount of the compound ly-1-25 to be prepared and the volume of the reaction vessel are enlarged or reduced in a corresponding ratio.

Example 3: preparation of Compound ly-1-117:

alpha-fluoro malonic acid monoethyl ester potassium salt (9.56 g, 50.8 mmol) and anhydrous magnesium chloride (8.8 g, 92.4 mmol) were dispersed in dry tetrahydrofuran, triethylamine (9.35 g, 92.4 mmol) was slowly added dropwise to the reaction flask under ice-bath conditions, after completion of the addition, the reaction was carried out at room temperature for 2 hours, then compound 1-1b (10.0 g, 46.2 mmol) was slowly added dropwise to the reaction flask under ice-bath conditions, after completion of the addition, the reaction was carried out at room temperature overnight, and the pH was adjusted to 1 with 3 mol/l hydrochloric acid and reacted at room temperature for 1 hour. After the reaction is completed. The mixture was allowed to stand for separation, the aqueous phase was extracted with ethyl acetate (3X 30 ml), the organic phases were combined, and the organic phase was washed successively with a saturated sodium bicarbonate solution, water and a saturated saline solution, and dried with anhydrous sodium sulfate. Vacuum filtering, concentrating, and performing column chromatography (V)_{Petroleum ether}∶V_{Ethyl acetate}20: 1-10: 1) to obtain a target product ly-1-117; the yield is 90 percent; the nuclear magnetic data are as follows:¹H NMR(400MHz，CDCl₃) δ 5.84(d, J ═ 48.1Hz, 1H), 4.35(q, J ═ 7.1Hz, 2H), 1.33(t, J ═ 7.1Hz, 3H). The amount of the compound ly-1-117 prepared and the volume of the reaction vessel are enlarged or reduced in a corresponding ratio.

The physicochemical and structural parameters of compound I are shown in Table 1.

Example 4: preparation of ethyl 3- (3, 4-dichloroisothiazol-5-yl) -3-oxopropanoate:

the preparation method comprises the steps of weighing monoethyl malonate potassium salt (0.84 g, 4.85 mmol) and anhydrous magnesium chloride (0.53 g, 5.54 mmol), placing the materials into a reaction bottle, stirring the materials with magnetons, adding 10.0 ml of tetrahydrofuran and under the protection of argon, dropwise adding triethylamine at the temperature of 0-25 ℃, and stirring the materials at room temperature for 1-2 hours. Dropwise adding a tetrahydrofuran-dissolved compound A (0.57 ml, 4.62 mmol) solution at a temperature of-5 to 25 ℃, and stirring at room temperature for 1 to 20 hours after the dropwise addition. After the reaction, 3 mol of dilute hydrochloric acid per liter is used for adjusting the pH value to 2-3, and then the reaction is carried out for 1-2 hours at room temperature. After the reaction is finished, adding a proper amount of water, extracting for 2-3 times by using ethyl acetate, combining organic phases, washing by using saturated saline solution, and drying by using anhydrous sodium sulfate. The organic solvent was distilled off to give E as a yellow solid. The amount of the compound can be enlarged or reduced according to the corresponding ratio, the range of the material ratio A to B is selected from any ratio between 1: 2 and 2: 1, the reaction time is selected from any time between 1 hour and 20 hours, the addition range of the material ratio A to C is selected from any ratio between 1: 1 and 1: 2, and typical experimental results after changing the conditions are shown in Table 2.

Example 5: the result of the determination of the antibacterial activity of the 3, 4-dichloroisothiazole-beta-keto acid ester derivative I is as follows:

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, PP: apple ring rot, its latin name is: physiosporia piricola, RS: rhizoctonia solani with the latin name: rhizoctonia solani, 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 3, and Table 3 shows that all the compounds synthesized by the invention have bactericidal activity of different degrees at 50 micrograms/ml. For rhizoctonia solani, the inhibition rates of the compounds LY01-11, LY01-25, LY01-108 and LY01-136 reach more than 80%, wherein the inhibition rates of the compounds LY01-11 and LY01-25 reach 100%, which are respectively higher than that of the control drugs azoxystrobin, pyraclostrobin, boscalid and isopyrazam by more than 40%, 20%, 30% and 20%; for apple ring rot germs, the compound has poor effect on the whole, and the inhibition rate is 15-46%. For sclerotinia sclerotiorum, the compound has poor effect on the whole, and the inhibition rate is 16-42%. The activity of the compound on the gibberella zeae shows that the compound has poor effect on the whole, the inhibition rate of the compound is 26-47%, and the compound is superior to a reference drug, namely the isopyrazam and is equivalent to the reference drug, namely the boscalid. For botrytis cinerea, the inhibition rate of compound LY01-11 reaches 56%, which is superior to that of the control azoxystrobin. For peanut brown spot germs, the compound has poor effect on the whole, and the inhibition rate is 30-50%. For the tomato early blight bacteria, the inhibition rates of compounds LY01-11 and LY01-25 reach 62% and 65%, and are superior to those of the control azoxystrobin. In conclusion, the compounds LY01-11 and LY01-25 show good bactericidal activity on rhizoctonia solani and early blight of tomato.

Example 6: the application of the 3, 4-dichloroisothiazole-beta-keto acid ester derivative I in preparing the pesticide composition comprises the following steps:

the 3, 4-dichloroisothiazole-beta-ketonic acid ester derivative I is used for preparing a pesticide composition, the composition contains the 3, 4-dichloroisothiazole-beta-ketonic acid ester derivative I and an intermediate thereof as active ingredients, and 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 7: the application of the 3, 4-dichloroisothiazole-beta-keto acid ester derivative I in preparing the pesticide compound composition comprises the following steps:

the 3, 4-dichloroisothiazole-beta-keto acid ester derivative I 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 3, 4-dichloroisothiazole-beta-keto acid ester derivative I and the intermediate thereof and other commercial pesticides, namely insecticides, acaricides, bactericides, antiviral agents or plant activators, as active ingredients, the 3, 4-dichloroisothiazole-beta-keto acid ester derivative I and the intermediate thereof are mixed with other commercial pesticides, namely insecticides, acaricides, bactericides, antiviral agents or plant activators in a ratio of 1 to 99 percent by mass to 1 percent by mass, and the content of the active ingredients is 0.1 to 99.9 percent by weight, 99.9% to 0.1% by weight of a solid or liquid adjuvant, and optionally 0 to 50% by weight of a surfactant.

Example 8: the application of the 3, 4-dichloroisothiazole-beta-keto acid ester derivative I and the pesticide composition in preventing and treating the agricultural and forestry and horticultural plant insect pests:

the 3, 4-dichloroisothiazole-beta-keto acid ester derivative I and any 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-beta-ketonic acid ester derivative I in the insecticidal composition is 1-90%, and the mass percentage of the 3, 4-dichloroisothiazole-beta-ketonic acid ester derivative I and the commercial insecticide is 1: 99-99: 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, 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.

Example 9: the application of the 3, 4-dichloroisothiazole-beta-keto acid ester derivative I and the bactericide in preventing and treating agricultural, forestry and horticultural plant diseases comprises the following steps:

the 3, 4-dichloroisothiazole-beta-keto acid ester derivative I and any one or two of commercial bactericides are combined to form a bactericidal composition for preventing and treating agricultural and forestry and horticultural plant diseases, wherein the commercial bactericides are selected from the following group: benzothiadiazole, tiadinil, thifluzamide, isotianil, ribavirin, antofine, ningnanmycin or salicylic acid, cymoxanil, thiram, mancozeb, fosetyl-aluminium, thiophanate-methyl, chlorothalonil, dichlorvos, procymidone, fenpropidin, thiophanate-methyl, metalaxyl-M, flumorphine, dimethomorph, metalaxyl-M, benalaxyl-M, dichlormid, sulfmate, thifluzamide, phyllophthal-des, cyprodinil, fenhexamid, fenpyrad, carboxin, oxycarboxin, mepanilate, metryzamide, triflumimide, furametpyr, thifluzamide, boscalide, penthiopyrad, isopyramide, flupyraflupyraflupyraclostrobin, fluopyram, epoxiconazole, flufenpyraclostrobin, flufenazamide, flufenacetrimol, propiconazole, iprodione, prochloraz, boscalid, pyraclostrobin, flufenacetrimonazide, thiflufenazamide, Fluxapyroxad, flufenacet amide, fluxafen, mandipropamid, zoxamide, ethiprole, iprodione, azoxystrobin, dimoxystrobin, fluoxastrobin, kresoxim-methyl, metominostrobin, fluoxastrobin, picoxystrobin, pyraclostrobin, trifloxystrobin, enestroburin, difenoconazole, epoxiconazole, bromuconazole, furconazole, cyproconazole, difenoconazole, diniconazole, epoxiconazole, fenbuconazole, fluquinconazole, flusilazole, flutriafol, hexaconazole, imibenconazole, ipconazole, metconazole, myclobutanil, penconazole, propiconazole, prothioconazole, simeconazole, tebuconazole, tetraconazole, triadimenol, bitertanol, thiabendazole, fuberidazole, imazalil, prochloraz, triflumizole, imazalone, imazalil, isoprothiolane, oxazofen, oxadixyl, imaza, Ethaboxam, hymexazol, octreotide, benthiocyanic, dodecacylmorpholine, fenpropimorph, tridemorph, fenpiclonil, fludioxonil, fluazinam, pyrifenox, cyprodinil, fluopicolide, pyrimethanil, cyprodinil, fluopyram, mepanipyrim, pyrimethanil, fenarimol, flufenarimol, imazamox, dithianon, ethoxyquin, hydroxyquinoline, propoxymidine, phenoxyquinoline, diethofencarb, iprovalicarb, benthiavalicarb, propamocarb, bendiocarb, iprobenfos, pyrazophos, tolon-methyl, blasticidin, kasugamycin, polyoxin, validamycin, streptomycin, metalaxyl, furalaxyl, benalaxyl, furalamide, carbendazim, benomyl, thiophanate-methyl, triadimefon, etridiazoline, dimerate, ethiofenphos, ethiprole, ethirimol, ethiprole, pencyazone, captopril, Folpet, vinclozolin, dichlorflupyr, dimethachlon, chlorothalonil, isoprothiolane, pyrifenozin, bismerthiazol, quintozene, propineb, fosetyl-aluminum, sulfur, boldo liquid, copper sulfate, copper oxychloride, cuprous oxide, copper hydroxide, metrafenone, pencycuron, pyridaben, tetrachlorophthalide, pyroquilon, spiroxamine, tricyclazole, fluazinam, dodine, iminoctadine, niclosamide, clononamid, tolbutamid, indoxyl, sodium diuron, quinacridone, probenazole, bronopol, methyl iodide, metam, dichlofenamate, dazomet, dazomethyl, dichloroisopropyl ether, fosthiazate, foscarnet, dichlofos, dichlofenthion, thiocarb, dichloropropenyl, dichloropropenonicin, probenazole; the 3, 4-dichloroisothiazole-beta-ketonic acid ester derivative I accounts for 1-90 percent of the total mass of the sterilization composition, and the 3, 4-dichloroisothiazole-beta-ketonic acid ester derivative I and the commercial bactericide account for 1 to 99 to 1 percent; the bactericidal composition is processed into a dosage form selected from the group consisting of: seed treatment emulsions, aqueous emulsions, microemulsions, suspoemulsions, capsule suspensions, water soluble granules, fine granules, soluble concentrates, venoms, block baits, granular baits, tablet baits, concentrated baits, sustained release blocks, electrostatic sprays, oil-in-water emulsions, aerosol cans, aerosol candles, aerosol cartridges, aerosol sticks, aerosol tablets, aerosol pellets, gas generants, ointments, hot fogging formulations, cold fogging formulations, aerosols, solid/liquid mixtures, liquid/liquid mixtures, solid/solid mixtures, lacquers, microgranules, chasing powders, oil suspensions, oil dispersible powders, concentrated gels, pour-on formulations, seed coatings, paints, film-forming oils, ultra-low volume liquids, vapor release agents; the plant diseases 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 10: the application of the 3, 4-dichloroisothiazole-beta-keto acid ester derivative I and the plant virus resisting agent in preventing and treating virus diseases of agricultural, forestry and horticultural plants is as follows:

the 3, 4-dichloroisothiazole-beta-keto acid ester derivative I and 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 medicament is selected from the following components: diazosulfide, tiadinil, isotianil, DL-beta-aminobutyric acid, ribavirin, antofine, ningnanmycin, methicillin or salicylic acid, pyriminomycin, dichloroisonicotinic acid, probenazole, validamycin, moroxydine hydrochloride; the 3, 4-dichloroisothiazole-beta-ketonic acid ester derivative I accounts for 1-90% of the total mass of the antiviral composition, and the 3, 4-dichloroisothiazole-beta-ketonic acid ester derivative I and the commodity plant virus resisting agent are in a ratio of 1-99-1% by mass; the dosage form processed by the antiviral composition is selected from the following components: 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 11: the application of the 3, 4-dichloroisothiazole-beta-ketonic acid ester derivative I and the acaricide in preventing and controlling the mite damage of agricultural, forestry and horticultural plants is as follows:

the 3, 4-dichloroisothiazole-beta-ketonic acid ester derivative I and any one or two of commercial acaricides form an acaricidal composition for preventing and controlling agricultural and forestry and horticultural plant acarids, wherein 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 3, 4-dichloroisothiazole-beta-ketonic acid ester derivative I accounts for 1-90% of the total mass percentage of the acaricidal composition, and the 3, 4-dichloroisothiazole-beta-ketonic acid ester derivative I and the commercial acaricide are in a ratio of 1: 99% to 99: 1% in mass percentage; the acaricidal composition is processed into a dosage form selected from the following: seed treatment emulsions, aqueous emulsions, microemulsions, suspoemulsions, capsule suspensions, water soluble granules, fine granules, soluble concentrates, venoms, block baits, granular baits, tablet baits, concentrated baits, sustained release blocks, electrostatic sprays, oil-in-water emulsions, aerosol cans, aerosol candles, aerosol cartridges, aerosol sticks, aerosol tablets, aerosol pellets, gas generants, ointments, hot fogging formulations, cold fogging formulations, aerosols, solid/liquid mixtures, liquid/liquid mixtures, solid/solid mixtures, lacquers, microgranules, chasing powders, oil suspensions, oil dispersible powders, concentrated gels, pour-on formulations, seed coatings, paints, film-forming oils, ultra-low volume liquids, vapor release agents; the mite damage controlled by the mite-killing composition is selected from the following groups: the mite is selected from spider mite family, furaciidae, goiter family, Tetranychus genus, and pest mites of the goiter family, which are world agricultural pest mites, forestry pest mites, horticultural pest mites, and health pest mites; the plant for 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 a 3, 4-dichloroisothiazole-beta-keto acid ester derivative I. 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 33 bacteriostatic activity of 4-dichloroisothiazole-beta-ketonic acid ester derivative I (inhibition rate of 50. mu.g/ml/%)

Serial number	Compound (I)	R.s	P.p	S.s	G.z	B.c	C.a	A.s
									1	LY01-11	100	28	32	45	56	45	62
2	LY01-25	100	46	42	43	47	48	65
									3	LY01-108	83	27	32	47	42	30	28
4	LY01-117	64	15	16	26	12	50	37
									5	LY01-136	87	33	32	47	48	30	40
6	Kresoxim-methyl	56	69	92	68	26	54	42
									7	Pyraclostrobin (Kresoxim-methyl)	80	81	100	86	90	83	70
8	Boscalid	67	67	96	44	100	100	100
									9	Pyrazolonaphthioides	73	88	94	21	100	100	96

R.s: rhizoctonia solani with the latin name: rhizoctonia solani, 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, C.a: peanut brown spot pathogen, its latin name is: cercospora arachidicola, A.s: tomato early blight, its latin name is: alternaria solani.

Claims

1. A3, 4-dichloroisothiazole-beta-ketonic acid ester derivative I is a 5- (3, 4-dichloroisothiazole) -beta-ketonic acid ester derivative, and is characterized by simultaneously containing a 3, 4-dichloroisothiazole heterocycle and a beta-ketonic acid ester structure, and the structural general formula is shown in formula I:

2. The specific synthetic route and method of the 3, 4-dichloroisothiazole-beta-keto acid ester derivative I according to claim 1 are as follows:

the first synthetic route of the 3, 4-dichloroisothiazole-beta-keto acid ester derivative I is as follows:

wherein R is¹Selected from: hydrogen, methyl, ethyl, fluorine, chlorine; r²Selected from: methyl, ethyl, alkyl;

in the first synthesis route, the synthesis of the compounds I-1 to I-3 can be divided into a condition A and a condition B according to reaction conditions;

wherein R is¹Selected from: hydrogen, methyl, ethyl; r²Selected from: methyl, ethyl, alkyl;

the second synthetic route of the 3, 4-dichloroisothiazole-beta-keto acid ester derivative I, namely the 5- (3, 4-dichloroisothiazole) -beta-keto acid ester derivative I, is as follows:

wherein R is¹Selected from: hydrogen, fluorine; r²Selected from: methyl, ethyl, alkyl;

the synthetic route III of the 5- (3, 4-dichloroisothiazole) -beta-keto acid ester derivative I-1 is as follows:

wherein R is²Selected from: methyl, ethyl, alkyl;

the synthesis route of the 3, 4-dichloroisothiazole-beta-keto acid ester derivative I-1, namely the 5- (3, 4-dichloroisothiazole) -beta-keto acid ester derivative I-1, is as follows:

wherein R is²Selected from: methyl, ethyl, alkyl;

in the fourth synthetic route, the synthesis of the compound I-1 can be divided into a condition C and a condition D according to reaction conditions;

wherein R is²Selected from: methyl, ethyl, alkyl;

the definition of the substituent is as defined in claim 1, and the specific synthetic method comprises the following steps:

the synthesis method of the 5- (3, 4-dichloroisothiazole) -beta-keto acid ester derivative I comprises the following steps:

synthesis of 5- (3, 4-dichloroisothiazole) -beta-keto acid ester derivative I:

route one condition a:

dissolving a compound II (5.0 g, 27.9 mmol) and zinc powder (4.56 g, 69.8 mmol) in 100 ml of dry tetrahydrofuran, adding methanesulfonic acid (135 mg, 1.4 mmol) at room temperature, refluxing the reaction solution for 15 minutes under the protection of nitrogen, slowly dropwise adding substituted ethyl bromoacetate (55.9 mmol), and continuing the reflux reaction for 1-3 hours after the dropwise addition is finished; monitoring the reaction by thin-layer chromatography, cooling to room temperature after the reaction is finished, andfiltering, dripping 30 ml of 3 mol/L hydrochloric acid at room temperature, stirring for 1 hour at room temperature, monitoring the reaction by thin-layer chromatography, and after the reaction is finished; standing for layering, extracting the water phase with ethyl acetate (3 × 30 ml), combining the organic phases, washing the organic phase with saturated sodium chloride solution, and adding anhydrous sodium sulfate for drying; vacuum filtering, concentrating, and performing column chromatography (V)_{Petroleum ether}∶V_{Ethyl acetate}Purifying at a ratio of 20: 1-10: 1) to obtain a target product I; the dosage of the compound can be enlarged or reduced according to the corresponding proportion, the material ratio II to the substituted bromoacetic acid alkyl ester is selected from any proportion between 1: 1 and 1: 5, the reaction time is selected from any time between 1 hour and 20 hours, the material ratio II to the zinc powder is selected from any proportion between 1: 1 and 1: 5, and the material ratio II to the methanesulfonic acid is selected from any proportion between 100: 1 and 10: 1;

route one condition B:

dissolving a compound II (5.0 g, 27.9 mmol) and zinc powder (4.56 g, 69.8 mmol) in 100 ml of dry tetrahydrofuran, adding cuprous bromide (200 mg, 1.4 mmol) and iodine (355 mg, 1.4 mmol) at room temperature under the protection of argon gas until the color of a reaction solution fades, refluxing the reaction solution for 15 minutes, slowly dropwise adding substituted bromoacetic acid alkyl ester (55.9 mmol), and continuously refluxing and reacting for 1-3 hours after dropwise adding is finished; monitoring the reaction by thin-layer chromatography, cooling to room temperature after the reaction is finished, filtering, dripping 30 ml of 3 mol/L hydrochloric acid at room temperature, stirring for 1 hour at room temperature, monitoring the reaction by thin-layer chromatography, and after the reaction is finished; standing for layering, extracting the water phase with ethyl acetate (3 × 30 ml), combining the organic phases, washing the organic phase with saturated sodium chloride solution, and adding anhydrous sodium sulfate for drying; vacuum filtering, concentrating, and performing column chromatography (V)_{Petroleum ether}∶V_{Ethyl acetate}Purifying at a ratio of 20: 1-10: 1) to obtain a target product I; the dosage of the compound can be enlarged or reduced according to the corresponding proportion, the material ratio II to the substituted alkyl bromoacetate is selected from any proportion between 1: 1 and 1: 5, the reaction time is selected from any time between 1 hour and 20 hours, the material ratio II to the zinc powder is selected from any proportion between 1: 1 and 1: 5, the material ratio II to the brominated imino ketone and the iodine is selected from 100: 1 to 10: 1Any ratio between 1: 1;

route one synthesis of 5- (3, 4-dichloroisothiazole) -beta-keto acid ester derivative I-4:

dissolving a compound I-1(18.7 mmol) in dry dichloromethane, dropwise adding sulfonyl chloride (7.55 g, 56.0 mmol) at room temperature, reacting at room temperature for 3 hours after dropwise adding, and then heating and refluxing for 3 hours; after the thin layer chromatography detection reaction is finished, the reaction solution is concentrated and subjected to column chromatography (V)_{Petroleum ether}∶V_{Ethyl acetate}Purifying at a ratio of 20: 1-10: 1) to obtain a target product I-4; the dosage of the compound can be enlarged or reduced according to the corresponding proportion, the range of the material ratio I-1: sulfonyl chloride is selected from any proportion between 1: 1 and 1: 5, and the reaction time is selected from any time between 1 hour and 20 hours;

route one synthesis of 5- (3, 4-dichloroisothiazole) -beta-keto acid ester derivative I-5:

compound I-1(18.7 mmol) is dissolved in dry acetonitrile and 1-chloromethyl-4-fluoro-1, 4-diazabicyclo [2.2.2 ] is added at room temperature]Octane bis (tetrafluoroborate) salt (19.64 mmol) was reacted under reflux for 3 hours; after the thin layer chromatography detection reaction is finished, the reaction solution is concentrated and subjected to column chromatography (V)_{Petroleum ether}∶V_{Ethyl acetate}20: 1-10: 1) to obtain a target product I-5; the dosage of the compound can be enlarged or reduced according to the corresponding proportion, and the material ratio is I-1: 1-chloromethyl-4-fluorine-1, 4-diazabicyclo [2.2.2]Octane bis (tetrafluoroborate) salt in a range selected from any ratio between 1: 1 to 1: 5 and a reaction time selected from any time between 1 hour to 20 hours;

route synthesis of bis 5- (3, 4-dichloroisothiazole) - β -keto acid ester derivative I:

dispersing compound IV (50.8 mmol) and anhydrous magnesium chloride (8.8 g, 92.4 mmol) in dry tetrahydrofuran, slowly adding triethylamine (9.35 g, 92.4 mmol) dropwise into a reaction bottle under ice bath conditions, reacting at room temperature for 2 hours after dropwise addition, slowly adding compound III (10.0 g, 46.2 mmol) dropwise into the reaction bottle under ice bath conditions, reacting at room temperature overnight after dropwise addition, and reacting at room temperature for 1 hour at the pH value of 1 by using 3 mol/L hydrochloric acid; after the reaction is finished; standing for layering, extracting the water phase with ethyl acetate (3 × 30 ml), mixing the organic phases, washing the organic phase with saturated sodium bicarbonate solution, water and saturated saline solution in sequence, and adding anhydrous sodium sulfate for drying; carrying out suction filtration and concentration to obtain a target product I; the dosage of the compound can be enlarged or reduced according to the corresponding proportion, the range of the material ratio III to IV is selected from any proportion between 1: 2 and 2: 1, the reaction time is selected from any time between 1 hour and 20 hours, and the range of the addition of the material ratio III to the magnesium chloride is selected from any proportion between 1: 1 and 1: 2;

route synthesis of tris 5- (3, 4-dichloroisothiazole) - β -keto acid ester derivative I-1:

dissolving Meldrum's acid (1.44 g, 10 mmol) with dichloromethane, stirring for 15 minutes under protection of argon, adding alkali (20 mmol) in an ice-water bath, dropwise adding compound III (2.17 g, 10 mmol) into the reaction solution, reacting at 0 ℃ for 1.5 hours, and continuing to react at room temperature for 3.0 hours; after the reaction is finished; acidifying with 3 mol/L hydrochloric acid, standing for layering, extracting the aqueous phase with dichloromethane (3 × 30 ml), combining the organic phases, washing the organic phase with water and saturated saline solution successively, and adding anhydrous sodium sulfate for drying; filtering, concentrating, and performing column chromatography (V)_{Methylene dichloride}∶V_MethanolPurifying at a ratio of 20: 1-10: 1) to obtain an intermediate V; the dosage of the compound can be enlarged or reduced according to the corresponding proportion, the range of the material ratio III to the Meldrum's acid is selected from any proportion between 1: 5 and 5: 1, the reaction time is selected from any time between 1 hour and 20 hours, and the range of the addition of the material ratio III to the alkali is selected from any proportion between 1: 5 and 5: 1;

dissolving the intermediate V (10 mmol) with alkyl alcohol, heating, refluxing and reacting overnight, and after the reaction is finished, concentrating the reaction solution to dryness to obtain a target compound I-1;

route synthesis of tetrakis 5- (3, 4-dichloroisothiazole) - β -keto acid ester derivative I-1:

route four condition C:

adding magnesium strip (292 mg, 12 mmol) and iodine simple substance (38 mg, 0.12 mmol) into a 100 ml three-neck flask, dissolving with carbon tetrachloride, adding a little ethanol, and allowing the reaction to be stableAfter the reaction is finished, adding a toluene solution of dialkyl malonate (12 mmol), reacting at room temperature, distilling the solvent under reduced pressure after magnesium strips completely disappear, carrying the solvent with toluene once, adding toluene as the solvent, dropwise adding a compound III (2.17 g and 10 mmol), and reacting at room temperature overnight; after the reaction is finished; acidifying with 3 mol/L hydrochloric acid, standing for layering, extracting the aqueous phase with ethyl acetate (3 × 30 ml), combining the organic phases, washing the organic phase with water and saturated saline solution successively, and adding anhydrous sodium sulfate for drying; filtering, concentrating, and performing column chromatography (V)_{Methylene dichloride}∶V_MethanolPurifying at a ratio of 20: 1-10: 1) to obtain an intermediate VI; the dosage of the compound can be enlarged or reduced according to the corresponding proportion, the range of the material ratio III to the dialkyl malonate is selected from any proportion between 1: 5 and 5: 1, the reaction time is selected from any time between 1 hour and 20 hours, and the adding amount range of the material ratio III to the magnesium to the iodine is selected from any proportion between 1: 5 and 100: 1;

route four condition D:

dispersing dialkyl malonate (50.8 mmol) and anhydrous magnesium chloride (8.8 g, 92.4 mmol) in dry tetrahydrofuran, slowly dropwise adding triethylamine (9.35 g, 92.4 mmol) into a reaction bottle under an ice bath condition, reacting at room temperature for 2 hours after dropwise adding, slowly dropwise adding compound III (10.0 g, 46.2 mmol) into the reaction bottle under an ice bath condition, reacting at room temperature overnight after dropwise adding, and reacting at room temperature for 1 hour at the pH value of 1 by adjusting 3 mol/L of hydrochloric acid; after the reaction is finished; standing for layering, extracting the water phase with ethyl acetate (3 × 30 ml), mixing the organic phases, washing the organic phase with water and saturated saline solution, adding anhydrous sodium sulfate, and drying; filtering, concentrating, and performing column chromatography (V)_{Methylene dichloride}∶V_MethanolPurifying at a ratio of 20: 1-10: 1) to obtain an intermediate VI; the dosage of the compound can be enlarged or reduced according to the corresponding proportion, the range of the material ratio III to the dialkyl malonate is selected from any proportion between 1: 5 and 5: 1, the reaction time is selected from any time between 1 hour and 20 hours, the adding amount range of the material ratio III to the magnesium chloride is selected from any proportion between 1: 5 and 5: 1, and the material ratio III to the triethylamineThe addition amount range is selected from any ratio between 1: 5 and 5: 1;

dissolving the intermediate VI (10 mmol) with alkyl alcohol, adding strong acid (hydrochloric acid, sulfuric acid and the like) as a catalyst, heating, refluxing and reacting overnight, and concentrating the reaction solution to dryness after the reaction is finished to obtain a target compound I-1;

the preparation amount of the compound I and the volume of a reaction vessel are enlarged or reduced according to corresponding proportion; the substituents are as defined in claim 1.

3. The use of the 3, 4-dichloroisothiazole- β -keto acid ester derivative I according to claim 1 for preparing an agricultural fungicide.

4. An agricultural fungicidal composition comprising the 3, 4-dichloroisothiazole- β -keto acid ester derivative I according to claim 1 and an intermediate, wherein the agricultural fungicidal composition comprises the 3, 4-dichloroisothiazole- β -keto acid ester 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 auxiliary agent, and optionally 0 to 25% by weight of a surfactant.

5. An agricultural sterilization compound composition, which comprises the 3, 4-dichloroisothiazole-beta-ketoacid ester derivative I as claimed in claim 1 and other commercial bactericides which are compounded to serve as active ingredients, wherein the proportion of the 5- (3, 4-dichloroisothiazole) -beta-ketoacid ester derivative I to the other commercial bactericides is 1 percent to 99 percent to 1 percent by mass, the content of the active ingredients is 1 to 99 percent by weight, and the content of the solid or liquid auxiliary agents is 99 to 1 percent by weight.

6. An agricultural insecticidal and acaricidal compound composition, which comprises the 3, 4-dichloroisothiazole-beta-ketoacid ester derivative I as claimed in claim 1 and other commercial insecticidal and acaricidal agents as active ingredients, wherein the proportion of the 5- (3, 4-dichloroisothiazole) -beta-ketoacid ester derivative I 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 active ingredients is 99 to 1% by weight of solid or liquid auxiliaries.

7. A compound composition of an anti-plant virus agent comprises the 3, 4-dichloroisothiazole-beta-keto acid ester derivative I and other commercial anti-plant virus agents, wherein the 3, 4-dichloroisothiazole-beta-keto acid ester derivative I is compounded with the other commercial anti-plant virus agents to serve as an active ingredient, the ratio of the 5- (3, 4-dichloroisothiazole) -beta-keto acid ester derivative I to the other commercial anti-plant virus agents is 1% to 99% to 1% by mass, the content of the active ingredient is 1 to 99% by weight, and the content of the active ingredient is 99 to 1% by weight of a solid or liquid auxiliary agent.