Thiazolo-piperidine-containing derivative as well as preparation method and application thereof

Abstract

The invention provides a thiazole-containing piperidine derivative as well as a preparation method and application thereof, and particularly relates to a derivative of which the chemical structural general formula is shown as a formula I: # imgabs0 #. The invention discloses the structural general formula and the synthesis method of the compound and application of the compound as an insecticide, a bactericide and a plant virus resisting agent. The invention also relates to application and a preparation method of the compound in preventing and treating insect pests, diseases and virus diseases of agricultural, forestry and horticultural plants in combination with agriculturally acceptable auxiliaries or synergists and commercial insecticides, bactericides, plant virus resisting agents and acaricides.

Description

Technical Field

[0001] The technical solution of the invention belongs to the field of pesticides, and specifically relates to thiazolopiperidine derivatives and preparation methods and uses thereof. Background Art

[0002] Green pesticides are strategic materials for the national economy and play an important role in ensuring crop yields and food security. However, with the extensive use of pesticides, problems such as resistance of pests and diseases, pesticide residues and environmental pollution have also arisen. Therefore, the creation of high-efficiency, low-residue and environmentally friendly pesticides has become a top priority in the creation of new pesticides (Shao Xusheng et al. World Pesticides, 2020, 42, 16-24).

[0003] Natural products refer to metabolites or secondary metabolites produced by plants, microorganisms and animals, and have characteristics such as structural diversity, biocompatibility and novel mechanisms. Natural products are one of the important sources of agricultural chemical leads. Thiazole is a heterocyclic compound widely found in natural products, with biological activities such as bactericidal, insecticidal, anti-tumor and antiviral. Cystothiazole A is a natural product isolated from the culture medium of the myxobacterium Cystobacter fuscus, which has good broad-spectrum fungicidal activity against five common plant pathogenic fungi (Ojika, M..et al. J. Antibiot. 1998, 51, 275–281.; Williams, DR et al. J. Org. Chem. 2001, 66, 8463–8469.); Bacillamide is a natural product isolated from the marine bacterium Bacillus endophyticus, which has good fungicidal activity against algae (Churro, C..et al. J. Appl. Phycol. 2009, 21, 429–442.; Aaron, MS et al. J. Nat. Prod. 2007, 70, 1793–1795.).

[0004] Piperidine is a saturated nitrogen-containing heterocyclic compound widely found in alkaloids. Under physiological conditions, the nitrogen atom on the piperidine ring will be ionized, which is beneficial to improving the bioavailability and water solubility of the compound. Many commercial pesticides contain piperidine structures, such as fenpropidin, piperidine and fluazifop-butyl.

[0005] In order to discover more efficient, broad-spectrum, low-toxic and non-cross-resistance pesticide lead and candidate compounds, the present invention combines thiazole and piperidine rings to design and synthesize a class of thiazolopiperidine derivatives, and conducts systematic screening and evaluation of biological activity. Summary of the invention

[0006] The technical problem to be solved by the present invention is to provide a method for synthesizing a new class of thiazolyl piperidine derivatives, to provide a method for determining the biological activity of such compounds in regulating agricultural, horticultural, sanitary and forestry plant pests and plant pathogens, and to provide the application of these compounds in the fields of agriculture, horticulture, forestry and sanitation.

[0007] The English abbreviations used in the present invention are as follows: pyrrolidine, i-PrOH, NH 4 CN (cyanamide), S 8 (sublimed sulfur), HATU (2-(7-azobenzotriazole)-N,N,N',N'-tetramethyluronium hexafluorophosphate), DIPEA (N,N-diisopropylethylamine), DCM (dichloromethane), HCl (hydrogen chloride), EA (ethyl acetate), EDCI (1-(3-dimethylaminopropyl)-3-ethylcarbodiimide), HOBT (1-hydroxybenzotriazole), Et 3 N(Triethylamine).

[0008] The technical solution adopted by the present invention to solve the technical problem is: the chemical structure of the thiazolopiperidine derivative having insecticidal, acaricidal, bactericidal, anti-plant virus activity and inducing plant disease resistance activity in the agricultural, horticultural and forestry fields is shown in I:

[0009] I:

[0010] Where R 1 Selected from: trifluoromethyl, trichloromethyl, cyclopropyl, phenyl, 3-chlorophenyl, 3,4-dichloroisothiazol-5-yl, 4-methyl-1,2,3-thiadiazol-5-yl, 3-(difluoromethyl)-1-methyl-1H-pyrazol-4-yl; R 2 Selected from: trifluoromethyl, trichloromethyl, cyclopropyl, phenyl, 2-bromophenyl, 3-bromophenyl, 4-bromophenyl, thien-2-yl, thiazol-2-yl, tert-butoxy, ethoxy, isopropoxy, butoxy, phenoxy, 4-methoxyphenoxy, 4-nitrophenoxy.

[0011] The synthetic route of the thiazolyl piperidine derivative I of the present invention is as follows:

[0012]

[0013] The synthesis method of the thiazolopiperidine derivative I of the present invention is divided into the following steps:

[0014] A. Preparation of Compound 1:

[0015] Compound 1 is prepared by heating reaction of N-tert-butyloxycarbonyl-4-piperidone, cyanamide and sublimed sulfur under the action of an organic base such as pyrrolidine:

[0016] A 500 ml three-necked flask was added with isopropanol (75 ml), N-tert-butyloxycarbonyl-4-piperidone (25.0 mmol) and pyrrolidine (26.2 mmol) in sequence at room temperature. The system was then heated to 55 degrees Celsius and the reaction continued at this temperature for 2 hours. The heating was then turned off and the system was allowed to return to room temperature. An isopropanol solution (75 ml) of cyanamide (26.2 mmol) and sublimed sulfur (3.1 mmol) were then added to the system. The system was then stirred and reacted at room temperature for 10 hours. The reaction of the raw material was monitored by thin layer chromatography. The solvent was then removed by concentration under reduced pressure. The mixture was purified by column chromatography using dichloromethane / methanol (20:1, volume ratio) as an eluent to obtain a white solid (16.0 mmol), i.e., compound 1.

[0017] B. Preparation of Compound Ia:

[0018] Compound Ia is prepared by stirring the reaction of compound 1 and compound 2 in the presence of 2-(7-azobenzotriazole)-N,N,N',N'-tetramethyluronium hexafluorophosphate and N,N-diisopropylethylamine at room temperature:

[0019] In a 100 ml single-necked flask, dichloromethane (10 ml), 2-(7-azobenzotriazole)-N,N,N',N'-tetramethyluronium hexafluorophosphate (7.4 mmol), and different substituted carboxylic acids R 1 -COOH (6.2 mmol) and N,N-diisopropylethylamine (12.3 mmol), stirred for 20 minutes, then added the compound 1 (6.8 mmol) obtained in the previous step to the system, and then the system continued to stir and react at room temperature for 10 hours, and the reaction of the raw materials was completed after monitoring by thin layer chromatography, and then the organic phase was washed with a saturated sodium chloride solution and dried with anhydrous sodium sulfate, and then concentrated under reduced pressure to remove the solvent, and purified by column chromatography with petroleum ether / ethyl acetate (1:1, volume ratio) as an eluent to obtain compound Ia; the carboxylic acid is selected from: trifluoroacetic acid, trichloroacetic acid, cyclopropylcarboxylic acid, benzoic acid, 3-chlorobenzoic acid, 3,4-dichloroisothiazole-5-carboxylic acid, 4-methyl-1,2,3-thiadiazole-5-carboxylic acid, 3-(difluoromethyl)-1-methyl-1H-pyrazole-4-carboxylic acid;

[0020] C. Preparation of Compound 3:

[0021] Compound 3 is prepared by reacting compound Ia with a solution of hydrogen chloride in ethyl acetate at room temperature:

[0022] In a 100 ml single-necked flask, compound Ia (5.0 mmol) obtained in the previous step was added to a 4 mol HCl ethyl acetate solution (30 ml) at room temperature, and then stirred for reaction for 15 minutes. After the reaction was completed, the filter cake was washed with ethyl acetate and dried to obtain a white powder (3.5 mmol), i.e., compound 3;

[0023] D. Preparation of Compound Ib:

[0024] Compound Ib is prepared by stirring and reacting compound 3 and compound 4 under the action of 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide, 1-hydroxybenzotriazole and triethylamine at room temperature:

[0025] Take a 100 ml single-necked flask, add dichloromethane (10 ml), 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide (1.8 mmol), 1-hydroxybenzotriazole (1.6 mmol) and different substituted carboxylic acids R in sequence at room temperature. 2 -COOH (1.6 mmol), after stirring for 20 minutes, triethylamine (4.7 mmol) and the intermediate 3 (1.5 mmol) obtained in the previous step were added to the system, and then the system was stirred for 10 hours at room temperature. The reaction of the raw materials was monitored by thin layer chromatography. After that, the organic phase was washed with a saturated sodium chloride solution and dried with anhydrous sodium sulfate, and then concentrated under reduced pressure to remove the solvent, and purified by column chromatography with petroleum ether / ethyl acetate (3:1, volume ratio) as an eluent to obtain compound Ib; the carboxylic acid is selected from the group consisting of trifluoroacetic acid, trichloroacetic acid, cyclopropylcarboxylic acid, benzoic acid, 2-bromobenzoic acid, 3-bromobenzoic acid, 4-bromobenzoic acid, thiophene-2-carboxylic acid, and thiazole-2-carboxylic acid;

[0026] E. Preparation of Compound Ic:

[0027] Compound Ic is prepared by reacting compound 3 with compound 5 under stirring at room temperature in the presence of triethylamine:

[0028] Take a 100 ml single-necked flask and add dichloromethane (10 ml), the intermediate 3 obtained in the previous step (0.3 mmol), triethylamine (0.3 mmol) and different substituted acyl chlorides ClCOO-R in sequence at room temperature. 2 (0.3 mmol), and then the system was stirred and reacted for 10 hours at room temperature. The reaction of the raw materials was monitored by thin layer chromatography. The organic phase was washed with a saturated sodium chloride solution and dried over anhydrous sodium sulfate. The solvent was then removed by concentration under reduced pressure and purified by column chromatography using petroleum ether / ethyl acetate (3:1, volume ratio) as an eluent to obtain compound Ic; the acyl chloride was selected from: ethoxycarbonyl chloride, isopropoxycarbonyl chloride, butoxycarbonyl chloride, phenoxycarbonyl chloride, 4-methoxyphenoxycarbonyl chloride, and 4-nitrophenoxycarbonyl chloride.

[0029] G. Uses of Thiazolopiperidine Derivatives I:

[0030] The present invention provides use of a thiazolopiperidine derivative I in preparing an insecticide.

[0031] The invention provides use of a thiazole-piperidine derivative I in preparing a fungicide. The fungi controlled by the fungicide are tomato early blight, cucumber gray mold, peanut brown spot, wheat fusarium, apple ring rot, rice sheath blight and rapeseed sclerotinia.

[0032] The present invention provides use of a thiazolopiperidine derivative I in preparing an anti-tobacco mosaic virus agent.

[0033] The invention provides the use of a thiazolopiperidine derivative I in preparing a plant immune activator for inducing tobacco resistance to tobacco mosaic virus and the use of a thiazolopiperidine derivative I in inducing Arabidopsis resistance to Arabidopsis downy mildew.

[0034] It should be noted that plant immune activators were also called plant activators or inducers in the past. They can induce host plants to produce broad-spectrum and long-lasting disease resistance.

[0035] The present invention provides a pesticide composition containing a thiazole piperidine derivative I which is suitable for preventing and controlling insect pests and pathogens of agricultural, forestry and horticultural plants and inducing plants to produce defense capabilities against plant pests and pathogens. The above-mentioned pesticide composition includes an agricultural fungicide composition, an agricultural insecticide composition, an agricultural anti-plant virus composition, and an agricultural plant immune activator composition. The composition contains the thiazole piperidine derivative described in claim 1 as an active ingredient; the composition contains 0.1% to 99.9% by weight of the active ingredient, 99.9% to 0.1% by weight of a solid or liquid adjuvant, and 0 to 25% by weight of a surfactant.

[0036] H. Compositions containing thiazolopiperidine derivatives I and uses thereof:

[0037] An agricultural composition is formed by combining thiazolopiperidine derivative I and commercial pesticides for application; the commercial pesticides are selected from: one or more of insecticides, fungicides, anti-plant virus agents, acaricides, and plant immune activators. The composition contains thiazolopiperidine derivative I and other commercial insecticides, fungicides, anti-plant virus agents, acaricides, and plant immune activators as active ingredients; the content of the active ingredient in the composition is 1%:99% to 99%:1% by weight, and the composite composition contains 1% to 99% by weight of active ingredients, 99% to 1% by weight of solid or liquid adjuvants, and 0 to 25% by weight of surfactants. The specific combination is as follows:

[0038] The thiazolopiperidine derivative I is combined with any one or two of the insecticides to form an insecticidal composition for controlling agricultural, forestry and horticultural plant pests;

[0039] The insecticide is selected from the group consisting of methoprene, dimethoate, acetamiprid, avermectin, mibemycin, avermectin, spinosad, tefluthrin, cypermethrin, cypermethrin, cypermethrin, deltamethrin, cypermethrin, β-cypermethrin, λ-cypermethrin, cypermethrin, allethrin, bifenthrin, permethrin, ether cypermethrin, flumethrin, cypermethrin, imidacloprid, nitenpyram, chlorthiazolin, thiacloprid, thiamethoxam, clothianidin, dinotefuran, clothianidin, datenam, diflubenzuron, diflubenzuron, flufenoxuron, acetamiprid, lufenuron, chlorpyrifos, flufenuron, polyflubenzuron, flufenuron , bisbenzenefluanid, chlorfluazuron, anthracene, bistrifluanid, furanfenozide, fenfenozide, chlorfenapyr, methoxyfenozide, chlorfenapyr, dichlorvos, quinalphos, pyridazine, leafhopper powder, carbaryl, pirimicarb, mefenamic acid, isoprocarb, cartap, fenbutyl, leaf flying powder, carbaryl, cartap, bromocriptine, hexythiazox, fenpyroximate, pyridabenzan, clofenazine, fenpyroximate, pyrimidine, pyridabenzan, clofenazine, fenpyroximate, pyrimidine, pyridabenzan, spirocyclon, spirocyclon, spirocyclon, triazotin, buprofezin, insecticide single, insecticide double, chlorantraniliprole, tetrachlorantraniliprole, flubendiamide, flucyram, cyanamide, butene flubendiamide, tolfenpyrad, bromofenapyr, pyrazinone, etoxazole, cypermethrin, pyridabenzan, pyriproxyfen, emamectin, pyrimidine;

[0040] The mass percentage of the thiazolin-piperidine derivative I in the insecticide composition is 1%-90%; preferably, the mass percentage of the thiazolin-piperidine derivative I to the insecticide is 1%:99% to 99%:1%;

[0041] The dosage form of the insecticide composition is selected from the group consisting of seed treatment emulsion, aqueous emulsion, microemulsion, suspoemulsion, capsule suspension, water-soluble granule, fine granule, soluble concentrate, poisonous grain, block poison bait, granular poison bait, sheet poison bait, concentrated poison bait, slow-release block, electrostatic spray, oil-in-water emulsion, smoke can, smoke candle, smoke tube, smoke stick, smoke sheet, smoke pill, gasifier, ointment, hot fog, cold fog, aerosol, solid / liquid mixed agent, liquid / liquid mixed agent, solid / solid mixed agent, lacquer, microgranule, tracking powder, oil suspension, oil dispersible powder, concentrated glue, pouring agent, seed coating agent, smear, film-forming oil agent, ultra-low volume liquid agent, steam release agent;

[0042] The plant pests controlled by the insecticide composition are selected from: fall armyworm, red spider, East Asian migratory locust, cloud-spotted locust, Chinese rice locust, Japanese yellow-spine locust, single-spined mole cricket, oriental mole cricket, rice thrips, tobacco thrips, greenhouse thrips, rice tube thrips, wheat tube thrips, greenhouse whitefly, Bemisia tabaci, black-tailed leafhopper, green leafhopper, cotton leafhopper, spotted wax cicada, brown planthopper, white-backed planthopper, gray planthopper, sugarcane flat-horned planthopper, cotton aphid, wheat aphid, wheat long-tube aphid, peach aphid, sorghum aphid, radish aphid, cotton scale, mulberry shield scale, arrow-pointed shield scale, pear round scale, white wax insect, red wax scale, Korean ball-hard scale , pear web bug, banana web bug, fine-horned flower bug, tiny flower bug, needle-edged bug, rice spider bug, rice brown bug, rice black bug, rice green bug, green stink bug, alfalfa stink bug, middle black stink bug, big lacewings, beautiful lacewings, Chinese lacewings, grain moth, clothes moth, yellow thorn moth, brown thorn moth, flat thorn moth, wheat moth, cotton pink bollworm, sweet potato wheat moth, diamondback moth, peach borer, soybean borer, peach borer, apple top leaf roller, brown-banded long leaf roller, quasi-small yellow leaf roller, striped stem borer, bean pod borer, corn borer, yellow stem borer, cabbage borer, rice leaf roller, striped stem borer, cotton leaf roller, peach borer, sticky insect, twill Noctuidae, rice borer, cotton bridgeworm, beet armyworm, stem borer, cotton bollworm, Dingdian diamond drill, small cutworm, large cutworm, yellow cutworm, thief moth, gypsy moth, sweet potato hawkmoth, bean hawkmoth, straight-striped rice hesperid, hidden grain hesperid, citrus swallowtail, jade-belt swallowtail, cabbage butterfly, ramie red admiral, ramie yellow admiral, bean sedge, Venus carabid, wrinkled sheath carabid, wheat ear carabid, ditch wireworm, fine-breasted wireworm, grain spot beetle, black skin beetle, citrus small borax, golden-margin borax, yellow mealworm, black mealworm, red flour beetle, mixed flour beetle, copper green exotic beetle, dark beetle, North China giant Black-gilled scarab beetle, mulberry longhorn beetle, star longhorn beetle, orange brown longhorn beetle, peach-necked longhorn beetle, big monkey leafworm, small monkey leafworm, yellow melon beetle, yellow-striped flea beetle, mung bean weevil, pea weevil, broad bean weevil, corn weevil, rice weevil, wheat sawfly, pear sawfly, yellow-banded ichneumon wasp, white-star ichneumon wasp of sticky insect, hanging cocoon ichneumon wasp of cotton bollworm, black-spotted warty ichneumon wasp of stem borer, mosquito, fly, horsefly, red wheat midge, yellow wheat midge, rice gall midge, citrus fruit fly, melon fruit fly, wheat leaf gray leafminer, American spotted leafminer, bean stalk black leafminer, wheat stalk fly, seed fly, onion fly, radish fly, skirt chasing fly, corn borer fly, and sticky insect;

[0043] The plants controlled by the insecticide composition are selected from the group consisting of: rice, wheat, barley, oats, corn, sorghum, sweet potato, potato, cassava, soybean, snow pea, broad bean, pea, mung bean, adzuki bean, cotton, sericulture, peanut, rapeseed, sesame, sunflower, beet, sugarcane, coffee, cocoa, ginseng, fritillaria, rubber, coconut, oil palm, sisal, tobacco, tomato, pepper, radish, cucumber, cabbage, celery, mustard tuber, beet, rapeseed, onion, garlic, watermelon, melon, cantaloupe, papaya, apple, citrus and peach, tea, wild vegetables, bamboo shoots, hops, pepper, banana, papaya, orchid, and bonsai.

[0044] The thiazolopiperidine derivative I is combined with any one or two of the fungicides to form a fungicide composition for preventing and controlling agricultural, forestry and horticultural plant diseases;

[0045] The fungicide is selected from the group consisting of benzothiadiazole, thiazolamide, thiazolamide, DL-β-aminobutyric acid, isothiopyrad, viravirin, anthofen, ningnanmycin or salicylic acid, cymoxanil, thiram, zinc thiram, mancozeb, ethyl phosphine aluminum, methyl thiophanate, chlorothalonil, dichlorobenzene, procymidone, fenpropidin, methyl thiophanate, thiophanate, metalaxyl, flumorph, dimethomorph, high-efficiency metalaxyl, high-efficiency bensulfuron, dichlorocyanamide, sulfaquinoxaline, sulfaquinoxaline, thiofluanid, chlorothalonil, cyproconazole, cyprodinil, cyfluanid, cyprodinil, cyanamide, cyprodinil ... Azopyraclostrobin, Fluoxathiapiprolin, Fluoxathiapiprolin, Isopropyltrifloxacin, Fluoxathiapiprolin, Fluoxathiapiprolin, Fluoxathiapiprolin, Dimethomorph, Zoxystrobin, Ethioprolin, Iprodione, Azoxystrobin, Dimethomorph, Fluoxathiapiprolin, Dimethomorph, Ethiostrobin ... azole, cyproconazole, difenoconazole, diniconazole, high-efficiency diniconazole, fluepiconazole, nitrobenazole, fluquinconazole, flusilazole, flutriafol, hexaconazole, imidazole, cyproconazole, metconazole, myclobutanil, penconazole, propiconazole, prothioconazole, silyfloxacin, tebuconazole, tetrafluconazole, triadimenol, trichlorfonazole, bifenthrin, thiabendazole, wheat spike, imazalil, high-efficiency imazalil, prochloraz, Flubaccon, cyazofamid, imidacloprid, oxacloprid, oxacloprid, oxacloprid, oxacloprid, oxacloprid, oxathiapiprolin, oxadixyl, oxathiapiprolin, oxathiapiprolin, oxathiapiprolin, oxathiapiprolin, oxathiapiprolin, oxathiapiprolin, oxathiapiprolin, oxathiapiprolin, oxathiapiprolin, oxathiapiprolin, oxathiapiprolin, oxathiapiprolin, oxathiapiprolin, oxathiapiprolin, oxathiapiprolin, oxathiapiprolin, oxathiapiprolin, oxathiapiprolin, oxathiapiprolin, oxathiapiprolin, oxathiapiprolin, oxathiapiprolin, oxathiapiprolin, oxathiapiprolin, oxathiapiprolin, oxathiapiprolin, oxathiapiprolin, oxathiapiprolin, oxathiapiprolin, oxathiapiprolin, Bensulfuron, furamide, carbendazim, benomyl, methyl thiophanate, triadimefon, ethiminol sulfonate, dimethoate, ethiminol, captan, foltan, vinyl sclerotin, fluchloric acid sclerotin, sclerotin, thiophanate-methyl, chlorothalonil, rice blast, rice blast, leaf chloranil, pentachloronitrobenzene, propineb, fosetyl-aluminum, sulfur, Bordeaux mixture, copper sulfate, copper oxychloride, cuprous oxide, copper hydroxide, bensulfuron, pencuron, pyraclostrobin, tetrachlorophthalide, pyroquilone, spiroxafil, tricyclazole, thiamethoxam, polypyrimidine, biguanide salt, biguanide octylamine, chloranil, benzylsulfuron, toluenesulfuron, indole ester, sodium sulfensulfuron, quinoline, allyl thiazole, bronopol, iodomethane, metamethylenetetramine, dazomethanil, dichloroisopropyl ether, thiathion, fensulfuron, chloranil,Oxamyl, sulfuryl fluoride, dichloropropylene, dichloroisonicotinic acid, allylisothiazole;

[0046] The total mass percentage of the thiazolyl piperidine derivative I in the bactericidal composition is 1%-90%; the mass percentage of the thiazolyl piperidine derivative I to the bactericide is 1%:99% to 99%:1%;

[0047] The dosage form of the bactericidal composition is selected from the group consisting of seed treatment emulsion, aqueous emulsion, microemulsion, suspoemulsion, capsule suspension, water-soluble granule, fine granule, soluble concentrate, poisonous grain, block poison bait, granular poison bait, sheet poison bait, concentrated poison bait, slow-release block, electrostatic spray, oil-in-water emulsion, smoke can, smoke candle, smoke tube, smoke stick, smoke sheet, smoke pill, gasifier, ointment, hot mist, cold mist, aerosol, solid / liquid mixed agent, liquid / liquid mixed agent, solid / solid mixed agent, lacquer, microgranule, tracking powder, oil suspension, oil dispersible powder, concentrated glue, pouring agent, seed coating agent, smear, film-forming oil agent, ultra-low volume liquid agent, steam release agent;

[0048] The plant diseases controlled by the bactericidal composition are selected from: rice seedling rot, tomato root rot, potato late blight, tobacco black shank, millet powdery mildew, grape downy mildew, lettuce downy mildew, cucumber downy mildew, cucumber anthracnose;

[0049] The plants suitable for the fungicidal composition are selected from the group consisting of: rice, wheat, barley, oats, corn, sorghum, sweet potato, potato, cassava, soybean, snow pea, broad bean, pea, mung bean, adzuki bean, cotton, sericulture, peanut, rapeseed, sesame, sunflower, beet, sugarcane, coffee, cocoa, ginseng, fritillaria, rubber, coconut, oil palm, sisal, tobacco, tomato, pepper, radish, cucumber, cabbage, celery, mustard tuber, beet, rapeseed, onion, garlic, watermelon, melon, cantaloupe, papaya, apple, citrus and peach, tea, wild vegetables, bamboo shoots, hops, pepper, banana, papaya, orchid, and bonsai.

[0050] The thiazolopiperidine derivative I is combined with any one or two of the antiviral agents to form an antiviral composition for preventing and controlling viral diseases of agricultural, forestry and horticultural plants;

[0051] The antiviral agent is selected from: benzothiadiazole, thiazolamide, isothiazolamide DL-β-aminobutyric acid, 2,6-dichloroisonicotinic acid, N-cyanomethyl-2-chloroisonicotinamide, allylisothiazole, ribavirin, anthofin, ningnanmycin, methiothiazolamide or salicylic acid, pyrimidine, dichloroisonicotinic acid, allylisothiazole, Jinggangmycin, guanidine hydrochloride;

[0052] The total mass percentage of the thiazolopiperidine derivative I in the antiviral composition is 1%-90%; preferably, the mass percentage of the thiazolopiperidine derivative I to the anti-plant virus agent is 1%:99% to 99%:1%;

[0053] The dosage form of the antiviral composition is selected from the group consisting of seed treatment emulsion, aqueous emulsion, microemulsion, suspoemulsion, capsule suspension, water-soluble granule, fine granule, soluble concentrate, poisonous grain, block poison bait, granular poison bait, sheet poison bait, concentrated poison bait, slow-release block, electrostatic spray, oil-in-water emulsion, smoke can, smoke candle, smoke tube, smoke stick, smoke sheet, smoke pill, gasifier, ointment, hot mist, cold mist, aerosol, solid / liquid mixed agent, liquid / liquid mixed agent, solid / solid mixed agent, lacquer, microgranule, tracking powder, oil suspension, oil dispersible powder, concentrated glue, pouring agent, seed coating agent, smear, film-forming oil agent, ultra-low volume liquid agent, steam release agent;

[0054] The virus diseases controlled by the antiviral composition are selected from: rice dwarf disease, yellow dwarf disease, stripe leaf blight, tomato fern leaf virus disease, pepper mosaic virus disease, tobacco vein necrosis virus disease, corn dwarf mosaic virus, cauliflower mosaic virus, citrus virus disease, Jianlan orchid leaf virus, and Jianlan ringspot virus;

[0055] The plants for prevention and treatment of the antiviral composition are selected from the group consisting of rice, wheat, barley, oats, corn, sorghum, sweet potato, potato, cassava, soybean, snow pea, broad bean, pea, mung bean, adzuki bean, cotton, sericulture, peanut, rapeseed, sesame, sunflower, beet, sugarcane, coffee, cocoa, ginseng, fritillaria, rubber, coconut, oil palm, sisal, tobacco, tomato, pepper, radish, cucumber, cabbage, celery, mustard tuber, beet, rapeseed, onion, garlic, watermelon, melon, cantaloupe, papaya, apple, citrus and peach, tea, wild vegetables, bamboo shoots, hops, pepper, banana, papaya, orchid, and bonsai.

[0056] The thiazolopiperidine derivative I is combined with any one or two of the acaricides to form an acaricidal composition for preventing and controlling acaricide damage in agriculture, forestry and horticultural plants;

[0057] The acaricide is selected from the group consisting of dichlorvos, heptylphos, cypermethrin, dibromophos, pyrimidophos, chlormethoxam, ethion, acaricide, phosalone, methyl pyrimidophos, quinalphos, aphidox, chlormethoxam, phosmet, flumethrin, bifenthrin, cyhalothrin, cyhalothrin, cyhalothrin, cyhalothrin, cyhalothrin, cyhalothrin, cyhalothrin, bifenthrin, fenthiocarb, butanone, oxamyl, cypermethrin, long-lasting cypermethrin, benomyl, chlormethrin ... Wei, butyralidone, cypermethrin, benzyl benzoate, bromocriptine, cyfluthrin, acequinoxaline, flumioxon, flufenoxuron, liuyangmycin, cypermethrin, thuringin, miticide, liuyangmycin, avermectin, doramectin, eprinomectin, ivermectin, selamectin, moxidectin, pyrethrin, nicotine, matrine, azadirachtin, rotenone, cypermethrin, pyraclostrobin, cypermethrin ...

[0058] The total mass percentage of the thiazolopiperidine derivative I in the acaricide composition is 1%-90%; the mass percentage of the thiazolopiperidine derivative I to the acaricide is 1%:99% to 99%:1%;

[0059] The dosage form of the acaricide composition is selected from the group consisting of seed treatment emulsion, aqueous emulsion, microemulsion, suspoemulsion, capsule suspension, water-soluble granule, fine granule, soluble concentrate, poisonous grain, block poison bait, granular poison bait, sheet poison bait, concentrated poison bait, slow-release block, electrostatic spray, oil-in-water emulsion, smoke can, smoke candle, smoke tube, smoke stick, smoke sheet, smoke pill, gasifier, ointment, hot fog, cold fog, aerosol, solid / liquid mixed agent, liquid / liquid mixed agent, solid / solid mixed agent, lacquer, microgranule, tracking powder, oil suspension, oil dispersible powder, concentrated glue, pouring agent, seed coating agent, smear, film-forming oil agent, ultra-low volume liquid agent, steam release agent;

[0060] The mite pests controlled by the acaricidal composition are selected from the group consisting of pests of Tetranychus, Tenebriophyidae, Furonematodes, Cynocephalus, Tetranychus, and Cynocephalus, and the pests are global agricultural pests, forestry pests, gardening pests, and hygiene pests;

[0061] The plants for the control of the acaricide composition are selected from the group consisting of rice, wheat, barley, oats, corn, sorghum, sweet potatoes, potatoes, cassava, soybeans, snow peas, broad beans, peas, mung beans, adzuki beans, cotton, sericulture, peanuts, rapeseed, sesame, sunflowers, sugar beets, sugar cane, coffee, cocoa, ginseng, fritillaria, rubber, coconut, oil palm, sisal, tobacco, tomatoes, peppers, radishes, cucumbers, cabbages, celery, mustard tubers, sugar beets, rapeseed, onions, garlic, watermelons, melons, cantaloupes, papayas, apples, citrus and peach trees, tea, wild vegetables, bamboo shoots, hops, peppers, bananas, papayas, orchids, and bonsai.

[0062] The biological activity of the thiazolopiperidine derivative I described in the present invention is determined as follows:

[0063] Determination of fungicidal activity of the thiazolopiperidine derivative I of the present invention:

[0064] The bactericidal or antibacterial activity of the thiazolopiperidine derivative I of the present invention is determined by a bacterial growth rate determination method, which specifically comprises the following steps: 1.8 mg of a sample is dissolved in 2 drops of dimethyl sulfoxide, and then diluted to 500 μg / ml of the drug with an aqueous solution containing a certain amount of Tween 20 emulsifier, 1 ml of each test drug is aseptically drawn into a culture dish, and then 9 ml of potato dextrose agar medium is added to each dish, and after being shaken well, a 50 μg / ml drug-containing plate is prepared, and a plate with 1 ml of sterilized water added is used as a blank control, and a plate with a diameter of 4 mm is used to measure the bactericidal or antibacterial activity of the thiazolopiperidine derivative I of the present invention is measured by a bacterial growth rate determination method, and specifically comprises the following steps: 1.8 mg of a sample is dissolved in 2 drops of dimethyl sulfoxide, and then diluted to 500 μg / ml of the drug with an aqueous solution containing a certain amount of Tween 20 emulsifier, 1 ml of each test drug is aseptically drawn into a culture dish, and then 9 ml of potato dextrose agar medium is added to each dish, and then 50 μg / ml of drug-containing plate is prepared after being shaken well, and a plate with 1 ml of sterilized water added is used as a blank control, and a plate with a diameter of 4 mm is used to measure the bactericidal or antibacterial activity of the thiazolopiperidine derivative I of the present invention ... Use a cork puncher to cut the bacterial disc along the outer edge of the hyphae, move it to the drug-containing plate, and place it in an equilateral triangle. Repeat each treatment 3 times, and place the culture dish in a constant temperature incubator at 24±1 degrees Celsius for cultivation. After the diameter of the control colony expands to 2-3 cm, investigate the expansion diameter of the bacterial disc of each treatment, calculate the average value, and calculate the relative inhibition rate by comparing with the blank control. The test strains are most of the typical plant pathogens that actually occur in the field in my country's agricultural production. Their codes and names are as follows: As: Tomato early blight pathogen, its Latin name is: Alternaria solani, Bc: Cucumber gray mold, its Latin name is: Botrytis cinerea, Ca: Peanut brown spot fungus, its Latin name is: Cercospora arachidicola, Fg: Grainaceous Fusarium, its Latin name is: Fusarium graminearum, Fv: Verticillium fusarium, its Latin name is: Fusarium verticillioides, Pp: Apple ring rot fungus, its Latin name is: Physalosporapiricola, Rs: Rice sheath blight fungus, its Latin name is: Rhizoctonia solani, Ss: Rapeseed Sclerotinia, its Latin name is: Sclerotinia sclerotiorum.

[0065] The present invention further specifically illustrates the synthesis, biological activity and application of thiazolopiperidine derivatives I through specific preparation and biological activity determination examples. The examples are only used to specifically illustrate the present invention but not to limit the present invention. In particular, the biological activity is only an example and not to limit the present invention. The specific implementation methods are as follows:

[0066] Example 1: Preparation of Compound I-6:

[0067] Take a 500 ml three-necked flask, add isopropanol (75 ml), N-tert-butyloxycarbonyl-4-piperidone (5.0 g, 25.0 mmol) and pyrrolidine (1.9 g, 26.2 mmol) in sequence at room temperature, then heat the system to 55 degrees Celsius, and continue to react at this temperature for 2 hours, then turn off the heating and wait for the system to return to room temperature, then add cyanamide (1.1 g, 26.2 mmol) isopropanol solution (75 ml) and sublimed sulfur (1.1 g, 3.1 mmol) to the system, then continue to stir the system at room temperature for 10 hours, and monitor the reaction of the raw materials by thin layer chromatography. Then, concentrate under reduced pressure to remove the solvent, and purify by column chromatography with dichloromethane / methanol (20:1, volume ratio) as eluent to obtain a white solid (6.4 g, 16.0 mmol), i.e., compound 1, with a yield of 64%.

[0068] To a 100 ml single-necked flask, dichloromethane (10 ml), 2-(7-azobenzotriazole)-N,N,N',N'-tetramethyluronium hexafluorophosphate (2.8 g, 7.4 mmol), 3,4-dichloroisothiazole-5-carboxylic acid (1.2 g, 6.2 mmol) and N,N-diisopropylethylamine (1.6 g, 12.3 mmol) were added in sequence. After stirring for 20 minutes, compound 1 (1.7 g, 6.8 mmol) obtained in the previous step was added to the system. Then the system continued to stir and react at room temperature for 10 hours. Thin layer chromatography monitored the complete reaction of the raw materials. The organic phase was then washed with a saturated sodium chloride solution and dried over anhydrous sodium sulfate. The solvent was then removed by concentration under reduced pressure and purified by column chromatography with petroleum ether / ethyl acetate (1:1, volume ratio) as the eluent to obtain a yellow solid (2.4 g, 5.6 mmol), i.e., compound I-6, with a yield of 92%.

[0069] Example 2: Preparation of Compound I-12:

[0070] Take a 100 ml single-necked flask and add the compound I-6 (2.1 g, 5.0 mmol) obtained in the previous step to a 4 mol hydrogen chloride ethyl acetate solution (30 ml) at room temperature. Then stir the reaction for 15 minutes. After the reaction is completed, filter and wash the filter cake with ethyl acetate. After drying, a white powder (1.3 g, 3.5 mmol) is obtained, namely compound 3, with a yield of 70%.

[0071] A 100 ml single-necked flask was added with dichloromethane (10 ml), 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide (186 mg, 0.969 mmol), 1-hydroxybenzotriazole (116 mg, 0.848 mmol) and benzoic acid (105 mg, 0.848 mmol) in sequence at room temperature. After stirring for 20 minutes, triethylamine (262 mg, 2.583 mmol) and the intermediate 3 (301 mg, 0.807 mmol) obtained in the previous step were added to the system. The system was then stirred at room temperature for 10 hours. The reaction of the raw material was monitored by thin layer chromatography. The organic phase was then washed with a saturated sodium chloride solution and dried over anhydrous sodium sulfate. The solvent was then removed by concentration under reduced pressure. The mixture was purified by column chromatography using petroleum ether / ethyl acetate (3:1, volume ratio) as the eluent to obtain a yellow solid (260 mg, 0.592 mmol), i.e., compound I-12, with a yield of 73%.

[0072] Example 3: Preparation of Compound I-18:

[0073] Take a 100 ml single-necked flask, add dichloromethane (10 ml), the intermediate 3 obtained in the previous step (100 mg, 0.269 mmol), triethylamine (29 mg, 0.282 mmol) and ethoxycarbonyl chloride (28 mg, 0.256 mmol) in turn at room temperature, and then continue to stir the system at room temperature for 10 hours. TLC monitoring shows that the reaction of the raw materials is complete. The organic phase is then washed with a saturated sodium chloride solution and dried over anhydrous sodium sulfate. The solvent is then removed by concentration under reduced pressure, and the compound is purified by column chromatography using petroleum ether / ethyl acetate (3:1, volume ratio) as an eluent to obtain a yellow solid compound (77 mg, 0.188 mmol), i.e., compound I-18, with a yield of 73%.

[0074] Example 4: Antibacterial activity test results of the thiazolopiperidine derivative I of the present invention:

[0075] The codes and names of the common plant pathogenic fungi tested by the present invention are as follows: As: Alternaria solani, Bc: Botrytis cinerea, Ca: Cercospora arachidicola, Fg: Fusarium graminearum, Fv: Fusarium verticillioides, Pp: Physalospora piricola, Rs: Rhizoctonia solani, Ss: Sclerotinia sclerotiorum. These strains are very representative and can represent most of the species of pathogens occurring in the field during agricultural production.

[0076] The results of the bacterial growth rate method are shown in Table 2, which shows that all the compounds synthesized in the present invention have different degrees of fungicidal activity. The present invention uses commercial fungicides such as thiophanate-methyl and pyraclostrobin as positive controls to carry out the determination of the biological activity of new compounds; the results show that the inhibition rates of compounds I-6, I-9, I-16, and I-19 on Rhizoctonia solani are all over 70%, among which the inhibition rate of compound I-19 is 82%, which is equivalent to the control thiophanate-methyl (inhibition rate is 87%), and the inhibition rates of compounds I-6, I-8, I-16, and I-19 on cucumber gray mold are all over 75%, which are better than the control thiophanate-methyl (inhibition rate is 29%), and the inhibition rate of compound I-6 on 7 plant pathogens is over 60%, and the inhibition rate on cucumber gray mold and peanut brown spot pathogen is over 75%; further EC 50 The measurements showed that the EC values ​​of I-6, I-8, I-16, I-19 and I-21 against cucumber gray mold 50 The values ​​ranged from 0.43 to 8.79 μg / mL, among which compound I-16 had an EC value of 0. 50 The EC 50 value was 31.55 μg / mL) and pyraclostrobin (EC 50 The EC values ​​of compounds I-6, I-16 and I-19 against Rhizoctonia solani were 1.70 μg / mL. 50 The values ​​ranged from 1.13 to 3.23 μg / mL. The EC values ​​of compound I-6 against five plant pathogenic fungi were 50 The values ​​ranged from 3.23 to 29.69 μg / mL, with broad-spectrum bactericidal activity.

[0077] Example 5: Application of the thiazolopiperidine derivative I of the present invention in combination with an insecticide in preventing and controlling insect pests in agriculture, forestry and horticultural plants:

[0078] The thiazolopiperidine derivative I of the present invention is combined with any one or two of commercial insecticides to form an insecticidal composition for controlling agricultural, forestry and horticultural plant pests. The commercial insecticide is selected from the group consisting of methoprene, dimethoate, acetamiprid, avermectin, mibemycin, avermectin, spinosad, tefluthrin, cypermethrin, high-efficiency cypermethrin, high-efficiency cypermethrin, tri-cyhalothrin, deltamethrin, cypermethrin, β-cypermethrin, λ-cypermethrin, dichlorophenoxyacetic acid, permethrin, allethrin, bifenthrin, permethrin, etherpermethrin, flumethrin, fluvalinate, pyrimethrin, chlorpyrifos ... Beethoprid, nitenpyram, chlorthiophene, thiacloprid, thiamethoxam, clothianidin, dimethoate, clothianidin, datenam, diflubenzuron, diflubenzuron, diflubenzuron, diflubenzuron, flufenoxuron, acetamiprid, lufenuron, chlorfenapyr, flufenoxuron, flufenoxuron, flufenoxuron, flufenoxuron, flufenoxuron, flufenoxuron, flufenoxuron, bistriflubenzuron, furanthinofen, fenfenoxadone, chlorfenapyr, methoxyfenoxadone, chlorfenapyr, chlorfenapyr, chlorfenapyr, chlorfenapyr, chlorfenapyr, chlorfenapyr, chlorfenapyr, chlorfenapyr, chlorfenapyr, chlorfenapyr, chlorfenapyr, quinalphos, pyridazine, leafhopper powder, carbaryl, pirimicarb, mefenamic acid, isoprocarb, cartap, fenbutylcarb, leaf flying powder, carbaryl, cartap, bromopyralid, hexathiapiprolin, fenpyrad, pyridabenzane, cypermethrin , butyrate uron, pymetrozine, spiroclofen, spirothiocarb, spirothiocarb, spirothiocarb, triazotin, buprofezin, dimethoate, dimethoate, chlorantraniliprole, tetrachlorvinphos, flubendiamide, flucyantraniliprole, cyantraniliprole, butene fipronil, tolfenpyrad, chlorfenapyr, pyrazinone, etoxazole, cypermethrin, pyriproxyfen, pyriproxyfen, emamectin, pyrimidine; the mass percentage of the thiazolinone-piperidin derivative I of the present invention in the insecticidal composition is 1%-90%, and the mass percentage of the thiazolinone-piperidin derivative I of the present invention to the aforementioned commercial insecticide is 1%:99% to 99%:1%; the dosage form processed by the insecticidal composition Selected from: seed treatment emulsion, aqueous emulsion, microemulsion, suspoemulsion, capsule suspension, water-soluble granule, fine granule, soluble concentrate, poisonous grain, block poison bait, granular poison bait, sheet poison bait, concentrated poison bait, slow-release block, electrostatic spray, oil-in-water emulsion, smoke can, smoke candle, smoke tube, smoke stick, smoke sheet, smoke pill, gasifier, ointment, hot mist, cold mist, aerosol, solid / liquid mixed agent, liquid / liquid mixed agent, solid / solid mixed agent, lacquer, microgranule, tracking powder, oil suspension, oil dispersible powder, concentrated glue, pouring agent, seed coating agent, smear, film-forming oil agent, ultra-low volume liquid agent, steam release agent;The insecticide composition is applicable to plant pests selected from the group consisting of fall armyworm, red spider, East Asian migratory locust, cloud-spotted locust, Chinese rice locust, Japanese yellow-spine locust, single-spined mole cricket, oriental mole cricket, rice thrips, tobacco thrips, greenhouse thrips, rice tube thrips, wheat tube thrips, greenhouse whitefly, Bemisia tabaci, black-tailed leafhopper, green leafhopper, cotton leafhopper, spotted wax cicada, brown planthopper, white-backed Planthoppers, gray planthoppers, sugarcane flat-horned planthoppers, cotton aphids, wheat aphids, wheat long-tubed aphids, peach aphids, sorghum aphids, radish aphids, cotton scale, mulberry shield scale, arrow-pointed shield scale, pear round scale, white wax insect, red wax scale, Korean ball-hard scale, pear web bug, banana web bug, fine-horned flower bug, tiny flower bug, needle-edge bug, rice spider bug, rice brown bug, rice black bug, rice green bug, green blind bug, alfalfa blind bug, Middle black blind bug, large lacewings, beautiful lacewings, Chinese lacewings, grain moth, clothes moth, yellow thorn moth, brown thorn moth, flat thorn moth, wheat moth, cotton bollworm, sweet potato moth, diamondback moth, peach borer, soybean borer, peach borer, apple top leaf roller, brown-banded long leaf roller, quasi-small yellow leaf roller, striped stem borer, bean pod borer, corn borer, yellow stem borer, cabbage borer, rice leaf roller , striped borer, cotton leaf roller, peach borer, armyworm, armyworm, rice borer, cotton bridge worm, beet armyworm, greater stem borer, cotton bollworm, Dingdian diamond drill, small cutworm, large cutworm, yellow cutworm, thief moth, gypsy moth, sweet potato hawkmoth, bean hawkmoth, straight-striped rice hesperid, hidden grain hesperid, citrus swallowtail, jade-belt butterfly, cabbage butterfly, ramie red admiral, ramie yellow admiral Butterfly, bean lycopersicum, Venus carabiner, wrinkled carabiner, wheat ear carabiner, groove wireworm, fine-breasted wireworm, grain spot beetle, black skin beetle, citrus small jellyfish, golden edge jellyfish, yellow mealworm, black mealworm, red flour beetle, mixed flour beetle, copper green beetle, dark beetle, North China black gill beetle, mulberry longhorn beetle, star longhorn beetle, orange brown longhorn beetle, pink neck longhorn beetle, big monkey leaf beetle, small Ape leaf beetle, yellow melon beetle, yellow striped flea beetle, mung bean weevil, pea weevil, broad bean weevil, corn weevil, rice weevil, wheat sawfly, pear fruit bee, yellow-banded ichneumon wasp, white-star ichneumon wasp, hanging cocoon ichneumon wasp, cotton bollworm tooth-lipped ichneumon wasp, black-spotted warty ichneumon wasp, mosquito, fly, horsefly, red wheat midge, yellow wheat midge, rice gall midge, citrus fruit fly, melon fruit fly, wheat leaf ash leafminer, American spotted leafminer flies, bean stalk black miners, wheat stalk flies, seed flies, onion flies, radish flies, umbrella skirt chasing flies, corn borer flies, armyworms; the insecticide composition is applicable to plants selected from: rice, wheat, barley, oats, corn, sorghum, sweet potatoes, potatoes, cassava, soybeans, snow peas, broad beans, peas, mung beans, adzuki beans, cotton, sericulture, peanuts, rapeseed, sesame, sunflower, beet, sugarcane, coffee, cocoa, ginseng, fritillaria, rubber, coconut, oil palm, sisal, tobacco, tomato, pepper, radish, cucumber, cabbage, celery, mustard tuber, beet, rapeseed, onion, garlic, watermelon, melon, cantaloupe, papaya, apple, citrus and peach trees, tea, wild vegetables, bamboo shoots, hops, pepper, banana, papaya, orchid, bonsai. ;

[0079] Example 6: Application of the thiazolopiperidine derivative I of the present invention in combination with a fungicide in preventing and controlling agricultural, forestry and horticultural plant diseases:

[0080] The thiazolopiperidine derivative I of the present invention is combined with any one or two of the commercial fungicides to form a fungicide composition for preventing and controlling agricultural, forestry and horticultural plant diseases. The commercial fungicides are selected from: benzothiadiazole, thiazolamide, thiazolamide, isothiazolamide, viravir, anthofin, ningnanmycin or salicylic acid, cymoxanil, thiram, zinc thiram, mancozeb, fosetyl-aluminum, methyl thiophanate, chlorothalonil, dichlorvos, procymidone, fenpropidin, methyl thiophanate, thiophanate, metalaxyl-methyl, flumorph, dimethomorph, high-efficiency metalaxyl, high-efficiency bensulfuron, dichlorocyanamide, sulfaquinoxaline, sulfaquinoxaline, thiofluanid, chlorothalonil, cyclamic acid, cyanamide, silthiophanate, carboxin, oxycarboxin, mefoam, furyl Amine, oxadiazine, flutolanil, furazolidone, thiofuranil, boscalid, penthiopyrad, pyraclostrobin, bixafen, fluopyram, fluoxazolidone, flutolanil, flutolanil, isopyram ... Fluoxastrobin, kresoxim-methyl, fenoxystrobin, oxazolidinone, pyraclostrobin, oxazolidinone, oxazolidinone, oxazolidinone, oxazolidinone, oxazolidinone, cyproconazole, fenpropimorph, diniconazole, high-efficiency diniconazole, epoxiconazole, nitrobenzene, fluquinconazole, flusilazole, flutriafol, hexaconazole, imipenem, cyproconazole, metconazole, myclobutanil, penconazole, propiconazole, prothioconazole, Silafluazole, tebuconazole, tetrafluanidazole, triadimenol, trichlorfon, bifenthrin, thiabendazole, wheat spike, imazalil, high-efficiency imazalil, prochloraz, triflumizole, cyazofamid, imidacloprid, oxamidazole, pyraclostrobin, oxadiazine, oxadiazine, trifloxystrobin, thiabendazole, oxadiazine, trifloxystrobin, thiabendazole, octhiazol, thiabendazole, dodecanone, fenpropimorph, tridecanone, seed dressing Fluazifop, fludioxonil, fluazifop, pyraclostrobin, fluopicolide ... Bacterial phosphorus, methyl tolclofos, blasticide, kasugamycin, polyoxin, polyoxin, validamycin, Jinggangmycin, streptomycin, metalaxyl, furalaxyl, bensulfuron, furamide, carbendazim, benomyl, methyl thiophanate, triadimefon, pyrimidine sulfonate, dimethylpyrimidine, pyrimidine, captan, captan, folpet, vinyl sclerotin, fluchloric acid sclerotin, sclerotin, thiophanate-methyl, chlorothalonil, chloronitrobenzene, propineb, fosetyl-aluminum, sulfur, Bordeaux mixture, copper sulfate, copper oxychloride, cuprous oxide, copper hydroxide, mefenamic acid, pentyclofosinate, pyridamyl, tetrachlorophthalide, pyroquinone, spiroxanil, tricyclazole, quinacridone, polypyrimidine, biguanide salt, biguanide amine, chlornitrile, benzylsulfuron, toluenesulfuron, indole ester, sodium sulfone,Quinclorac, allylbenzazole, bronopol, iodomethane, metamethylenetetracycline, dazomethan, dichloroisopropyl ether, thiazothion, fenthiophos, cypermethrin, dimethoate, butyralidone, oxamyl, sulfuryl fluoride, dichloropropylene, dichloroisonicotinic acid, allylisothiazole; the total mass percentage of the thiazolinone-containing piperidine derivative I in the fungicide composition is 1%-90%, and the amount percentage of the thiazolinone-containing piperidine derivative I of the present invention to the aforementioned commercial fungicide is 1%:99% to 99%:1%; The dosage form of the bactericidal composition is selected from: seed treatment emulsion, aqueous emulsion, microemulsion, suspoemulsion, capsule suspension, water-soluble granules, fine granules, soluble concentrate, poison valley, block poison bait, granular poison bait, sheet poison bait, concentrated poison bait, slow-release block, electrostatic spray, oil-in-water emulsion, smoke can, smoke candle, smoke tube, smoke stick, smoke sheet, smoke pill, gasifier, ointment, hot fog, cold fog, aerosol, solid / liquid mixed agent, liquid / liquid mixed agent, solid / solid mixed agent, medicine The present invention relates to a kind of fungicide composition, which is suitable for the following plant diseases: rice seedling rot, tomato root rot, potato late blight, tobacco black shank, millet powdery mildew, grape downy mildew, lettuce downy mildew, cucumber downy mildew, cucumber anthracnose; the plants suitable for the fungicide composition are selected from the group consisting of rice, wheat, barley, oats, corn, sorghum, sweet potato, etc. Potatoes, potatoes, cassava, soybeans, snow peas, broad beans, peas, mung beans, red beans, cotton, sericulture, peanuts, rapeseed, sesame, sunflowers, beets, sugar cane, coffee, cocoa, ginseng, Fritillaria, rubber, coconut, oil palm, sisal, tobacco, tomatoes, peppers, radishes, cucumbers, cabbage, celery, mustard tubers, beets, rapeseed, onions, garlic, watermelons, melons, cantaloupes, papayas, apples, citrus and peaches, tea, wild vegetables, bamboo shoots, hops, peppers, bananas, papayas, orchids, bonsai.

[0081] Example 7: Application of the combination of the thiazolopiperidine derivative I of the present invention and an anti-plant virus agent in preventing and controlling viral diseases of agricultural, forestry and horticultural plants:

[0082] The thiazolopiperidine derivative I of the present invention is combined with any one or two of commercial antiviral agents to form an antiviral composition for preventing and controlling viral diseases of agricultural, forestry and horticultural plants. The commercial antiviral agent is selected from: benzothiadiazole, thiazolamide, isothiazolamide, ribavirin, anthofin, ningnanmycin, methiazolamide or salicylic acid, pyrimidine, dichloroisonicotinic acid, allylisothiazole, jinggangmycin, and guanidine hydrochloride; the total mass percentage of the thiazolopiperidine derivative I of the present invention in the antiviral composition is 1%-90%, and the thiazolopiperidine derivative I of the present invention is 1%-90%. The ratio of the azole piperidine derivative I to the aforementioned commercial anti-plant virus agent is 1%:99% to 99%:1% by mass; the dosage form processed by the anti-virus composition is selected from: seed treatment emulsion, aqueous emulsion, microemulsion, suspoemulsion, capsule suspension, water-soluble granules, fine granules, soluble concentrate, poison valley, block poison bait, granular poison bait, sheet poison bait, concentrated poison bait, slow-release block, electrostatic spray, water-in-oil emulsion, smoke can, smoke candle, smoke tube, smoke stick, smoke sheet, smoke pill, gasifier, ointment, hot fog agent, cold fog agent, aerosol, solid / liquid mixture The invention relates to a composition comprising a composition for preventing and treating viral diseases, a liquid / liquid mixed composition, a solid / solid mixed composition, a lacquer, a microgranule, a tracking powder, an oil suspension, an oil dispersible powder, a concentrated gel, a pouring agent, a seed coating agent, a smear, a film-forming oil agent, an ultra-low volume liquid agent, and a steam release agent; the viral diseases prevented and treated by the antiviral composition are selected from the group consisting of: rice dwarf disease, yellow dwarf disease, stripe leaf blight, tomato fern leaf virus disease, pepper mosaic virus disease, tobacco vein necrosis virus disease, corn dwarf mosaic disease, cauliflower mosaic virus, citrus virus disease, Jianlan orchid leaf virus, and Jianlan ringspot virus; the antiviral composition is used to prevent and treat plants Selected from: rice, wheat, barley, oats, corn, sorghum, sweet potato, potato, cassava, soybean, snow pea, broad bean, pea, mung bean, adzuki bean, cotton, sericulture, peanut, rapeseed, sesame, sunflower, beet, sugarcane, coffee, cocoa, ginseng, fritillaria, rubber, coconut, oil palm, sisal, tobacco, tomato, pepper, radish, cucumber, cabbage, celery, mustard tuber, beet, rapeseed, onion, garlic, watermelon, melon, cantaloupe, papaya, apple, citrus and peach trees, tea, wild vegetables, bamboo shoots, hops, pepper, banana, papaya, orchid, bonsai.

[0083] Example 8: Application of the combination of the thiazolopiperidine derivative I of the present invention and acaricide in preventing and controlling mite damage in agriculture, forestry and horticultural plants:

[0084] The thiazolopiperidine derivative I of the present invention is combined with any one or two of the commercial acaricides to form an acaricide composition for preventing and controlling mite pests in agriculture, forestry and horticultural plants. The commercial acaricide is selected from the group consisting of dichlorvos, heptylphos, cypermethrin, dibromophos, pyrimidophos, chlormethoxam, ethion, cypermethrin, phosalone, methyl pyrimidophos, quinalphos, aphidox, chlormethoxam, chlormethoxam, phosmet, flumethoxam, acralthrin, bifenthrin, cyhalothrin, cyhalothrin, cyhalothrin, cyhalothrin, cyhalothrin, cyhalothrin, cyhalothrin, bifenthrin, fenthiocarb, butanone, oxamyl, cypermethrin, long-lasting carb, benomyl, chlormethoxam, butanone, cypermethrin, benzyl benzoate, bromothioate, Cyflumetofen, acequinoxaline, fluazifop, flufenoxuron, liuyangmycin, acaricide, thuringin, acaricide, liuyangmycin, avermectin, doramectin, eprinomectin, ivermectin, selamectin, moxidectin, pyrethrin, nicotine, matrine, azadirachtin, rotenone, tebufenamide, pyridabenzamide, fenpyraclostrobin, clofenazine, fenpropathrin, hexythiazox, spirocyclopentyl, pyrimidine, fenpyraclostrobin, fenpyraclostrobin, propargite, pyridabenzamide; the total mass percentage of the thiazolopiperidone derivative I in the acaricide composition is 1%-90%, and the ratio of the thiazolopiperidone derivative I to the commercial acaricide is 1%:99% to 99%:1% by mass; the formulation of the acaricide composition is selected from: seeds Treatment emulsion, aqueous emulsion, microemulsion, suspoemulsion, capsule suspension, water-soluble granule, fine granule, soluble concentrate, poison valley, block bait, granular bait, sheet bait, concentrated bait, slow-release block, electrostatic spray, oil-in-water emulsion, smoke can, smoke candle, smoke tube, smoke stick, smoke sheet, smoke pill, gasifier, ointment, hot mist, cold mist, aerosol, solid / liquid mixed agent, liquid / liquid mixed agent, solid / solid mixed agent, lacquer, microgranule, tracking powder, oil suspension, oil dispersible powder, concentrated glue, pouring agent, seed coating agent, smear, film-forming oil, ultra-low volume liquid, steam release agent; the mite pests controlled by the acaricide composition are selected from: the mite pests are selected from Tetranychus, Tenebriophyidae, Furonematodes, Gall Mites, Red Pest mites of the genus Tetranychus and the family Tetranychus, which are global agricultural pests, forestry pests, gardening pests and sanitary pests; the plants for which the miticide composition is used to control are selected from the group consisting of rice, wheat, barley, oats, corn, sorghum, sweet potatoes, potatoes, cassava, soybeans, snow peas, broad beans, peas, mung beans, adzuki beans, cotton, sericulture, peanuts, rapeseed, sesame, sunflowers, sugar beets, sugar cane, coffee, cocoa, ginseng, fritillaria, rubber, coconut, oil palm, sisal, tobacco, tomatoes, peppers, radishes, cucumbers, cabbages, celery, mustard tubers, sugar beets, rapeseed, onions, garlic, watermelons, melons, cantaloupes, papayas, apples, citrus and peach trees, tea, wild vegetables, bamboo shoots, hops, peppers, bananas, papayas, orchids and bonsai.

[0085] Example 9: Application of the thiazolopiperidine derivative I of the present invention in the preparation of a pesticide composition:

[0086] The pesticide composition prepared by the thiazole-piperidine derivative I of the present invention contains the thiazole-piperidine derivative I of the present invention as an active ingredient, the mass percentage of the active ingredient is 0.1% to 99.9%, the mass percentage of a solid or liquid auxiliary agent is 99.9% to 0.1%, and further contains an optional surfactant in an amount of 0 to 25% by mass.

[0087] Example 10: Application of the thiazolopiperidine derivative I of the present invention in the preparation of a pesticide compound composition:

[0088] The thiazolyl piperidine derivative I of the present invention can be compounded with other commercial pesticides, i.e., insecticides, miticides, fungicides, antiviral agents or plant immune activators to prepare a pesticide compound composition. The compound composition comprises the thiazolyl piperidine derivative I of the present invention and commercial pesticides, i.e., insecticides, miticides, fungicides, antiviral agents or plant immune activators as active ingredients. The ratio of the thiazolyl piperidine derivative I of the present invention to the other commercial pesticides, i.e., insecticides, miticides, fungicides, antiviral agents or plant immune activators is 1%:99% to 99%:1% by mass, the mass percentage of the active ingredient is 0.1% to 99.9%, 99.9% to 0.1% by mass of solid or liquid adjuvants, and optionally 0 to 25% by mass of surfactants.

[0089] Industrial Applicability

[0090] The present invention provides a class of thiazolopiperidine derivatives; the derivatives of the present invention can regulate the biological activities of agricultural, horticultural, sanitary and forestry plant pests and plant pathogens, can be used in the agricultural, horticultural and forestry fields to kill insects, mites, bacteria, resist plant viruses, and induce plants to produce disease resistance, and have good economic value and application prospects.

[0091] Table 1 Chemical structures and physicochemical parameters of thiazolyl piperidine derivatives of the present invention

[0092]

[0093] Table 2 Antibacterial activity of thiazolopiperidine derivatives I of the present invention (inhibition rate at 50 μg / ml / %)

[0094]

[0095] As: Tomato early blight pathogen, its Latin name is: Alternaria solani, Bc: Cucumber gray mold pathogen, its Latin name is: Botrytis cinerea, Ca: Peanut brown spot pathogen, its Latin name is: Cercospora arachidicola, Fg: Grainaceous Fusarium graminearum, Fv: Verticillium fusarium, its Latin name is: Fusarium verticillioides, Pp: Apple ring rot pathogen, its Latin name is: Physalosporapiricola, Rs: Rice sheath blight pathogen, its Latin name is: Rhizoctonia solani, Ss: Rapeseed sclerotinia pathogen, its Latin name is: Sclerotinia sclerotiorum.

[0096] Table 3 Results of precise toxicity determination of antibacterial activity of thiazolopiperidine derivatives I of the present invention (EC 50 :μg / mL)

[0097]

Claims

1. A class of thiazolyl piperidine derivatives having the general structural formula shown in Formula I: in, R 1 Selected from: trifluoromethyl, trichloromethyl, cyclopropyl, phenyl, 3-chlorophenyl, 3,4-dichloroisothiazol-5-yl, 4-methyl-1,2,3-thiadiazol-5-yl, 3-(difluoromethyl)-1-methyl-1H-pyrazol-4-yl; R 2 Selected from: trifluoromethyl, trichloromethyl, cyclopropyl, phenyl, 2-bromophenyl, 3-bromophenyl, 4-bromophenyl, thien-2-yl, thiazol-2-yl, tert-butoxy, ethoxy, isopropoxy, butoxy, phenoxy, 4-methoxyphenoxy, 4-nitrophenoxy.

2. The specific synthetic route and method of the thiazolopiperidine derivative I according to claim 1 are: The definition of the substituent is as described in claim 1, and the specific synthesis method is divided into the following steps: Compound 1 is prepared by heating reaction of N-tert-butyloxycarbonyl-4-piperidone, cyanamide and sublimed sulfur under the action of an organic base such as pyrrolidine; Compound Ia is prepared by stirring reaction of Compound 1 and Compound 2 under the action of 2-(7-azobenzotriazole)-N,N,N',N'-tetramethyluronium hexafluorophosphate and N,N-diisopropylethylamine at room temperature; Compound 3 is prepared by reacting Compound Ia and ethyl acetate solution of hydrogen chloride at room temperature; Compound Ib is prepared by stirring reaction of Compound 3 and Compound 4 under the action of 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide, 1-hydroxybenzotriazole and triethylamine at room temperature; Compound Ic is prepared by stirring reaction of Compound 3 and Compound 5 under the action of triethylamine at room temperature; A. Preparation of Compound 1: A 500 ml three-necked flask was used to sequentially add isopropanol (75 ml), N-tert-butyloxycarbonyl-4-piperidone (25.0 mmol) and pyrrolidine (26.2 mmol) at room temperature. The system was then heated to 55 degrees Celsius and the reaction continued at this temperature for 2 hours. The heating was then turned off and the system was allowed to return to room temperature. An isopropanol solution (75 ml) of cyanamide (26.2 mmol) and sublimed sulfur (3.1 mmol) were then added to the system. The system was then stirred and reacted at room temperature for 10 hours. The reaction of the raw material was monitored by thin layer chromatography. The solvent was then removed by concentration under reduced pressure. The mixture was purified by column chromatography using dichloromethane / methanol (20:1, volume ratio) as an eluent to obtain a white solid (16.0 mmol), namely, intermediate 1. B. Preparation of Compound Ia: In a 100 ml single-necked flask, dichloromethane (10 ml), 2-(7-azobenzotriazole)-N,N,N',N'-tetramethyluronium hexafluorophosphate (7.4 mmol), and different substituted carboxylic acids R 1 -COOH (6.2 mmol) and N,N-diisopropylethylamine (12.3 mmol), stirred for 20 minutes, then added the compound 1 (6.8 mmol) obtained in the previous step to the system, and then the system continued to stir and react for 10 hours at room temperature, and the reaction of the raw materials was completed after monitoring by thin layer chromatography, and then the organic phase was washed with a saturated sodium chloride solution and dried with anhydrous sodium sulfate, and then concentrated under reduced pressure to remove the solvent, and purified by column chromatography with petroleum ether / ethyl acetate (1:1, volume ratio) as an eluent to obtain compound Ia; the carboxylic acid is selected from: trifluoroacetic acid, trichloroacetic acid, cyclopropylcarboxylic acid, benzoic acid, 3-chlorobenzoic acid, 3,4-dichloroisothiazole-5-carboxylic acid, 4-methyl-1,2,3-thiadiazole-5-carboxylic acid, 3-(difluoromethyl)-1-methyl-1H-pyrazole-4-carboxylic acid; C. Preparation of Compound 3: In a 100 ml single-necked flask, compound Ia (5.0 mmol) obtained in the previous step was added to a 4 mol HCl ethyl acetate solution (30 ml) at room temperature, and then stirred for reaction for 15 minutes. After the reaction was completed, the filter cake was washed with ethyl acetate and dried to obtain a white powder (3.5 mmol), i.e., compound 3; D. Preparation of Compound Ib: Take a 100 ml single-necked flask and add dichloromethane (10 ml), 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide (1.8 mmol), 1-hydroxybenzotriazole (1.6 mmol) and different substituted carboxylic acids R in sequence at room temperature. 2 -COOH (1.6 mmol), after stirring for 20 minutes, triethylamine (4.7 mmol) and the intermediate 3 (1.5 mmol) obtained in the previous step were added to the system, and then the system was stirred for 10 hours at room temperature. The reaction of the raw materials was monitored by thin layer chromatography. After that, the organic phase was washed with a saturated sodium chloride solution and dried with anhydrous sodium sulfate, and then concentrated under reduced pressure to remove the solvent, and purified by column chromatography with petroleum ether / ethyl acetate (3:1, volume ratio) as an eluent to obtain compound Ib; the carboxylic acid is selected from the group consisting of trifluoroacetic acid, trichloroacetic acid, cyclopropylcarboxylic acid, benzoic acid, 2-bromobenzoic acid, 3-bromobenzoic acid, 4-bromobenzoic acid, thiophene-2-carboxylic acid, and thiazole-2-carboxylic acid; E. Preparation of Compound Ic: Take a 100 ml single-necked flask and add dichloromethane (10 ml), the intermediate 3 obtained in the previous step (0.7 mmol), triethylamine (2.2 mmol) and different substituted acyl chlorides ClCOO-R in sequence at room temperature. 2 (0.6 mmol), and then the system was stirred and reacted at room temperature for 10 hours. The reaction of the raw materials was monitored by thin layer chromatography. The organic phase was washed with a saturated sodium chloride solution and dried over anhydrous sodium sulfate. The solvent was then removed by concentration under reduced pressure and purified by column chromatography using petroleum ether / ethyl acetate (3:1, volume ratio) as an eluent to obtain compound Ic; the acyl chloride was selected from: ethoxycarbonyl chloride, isopropoxycarbonyl chloride, butoxycarbonyl chloride, phenoxycarbonyl chloride, 4-methoxyphenoxycarbonyl chloride, and 4-nitrophenoxycarbonyl chloride.

3. Use of the thiazolopiperidine derivative according to claim 1 in the preparation of an agricultural fungicide, wherein the fungi controlled by the fungicide are tomato early blight, cucumber gray mold, peanut brown spot, wheat fusarium, apple ring rot, rice sheath blight, and rapeseed sclerotinia.

4. Use of the thiazolopiperidine derivative according to claim 1 in the preparation of an agricultural plant immune activator, wherein the plant immune activator is used to control Arabidopsis downy mildew.

5. An agricultural fungicide composition, comprising the thiazolopiperidine derivative according to claim 1 as an active ingredient; The composition comprises 0.1% to 99.9% by weight of active ingredients, 99.9% to 0.1% by weight of solid or liquid adjuvants, and 0 to 25% by weight of a surfactant.

6. An agricultural fungicide compound composition, which comprises the thiazolyl piperidine derivative according to claim 1 and other commercial fungicides as active ingredients; the ratio of the thiazolyl piperidine derivative to the other commercial fungicides is 1%:99% to 99%:1% by weight, and the compound composition comprises 1% to 99% by weight of the active ingredient, 99% to 1% by weight of a solid or liquid adjuvant, and 0 to 25% by weight of a surfactant.

7. An agricultural insecticide and acaricide compound composition, which comprises the thiazolyl piperidine derivative according to claim 1 and other commercial fungicides as active ingredients; the ratio of the thiazolyl piperidine derivative to the other commercial insecticides and acaricides is 1%:99% to 99%:1% by weight, and the compound composition comprises 1% to 99% by weight of the active ingredient, 99% to 1% by weight of a solid or liquid adjuvant, and 0 to 25% by weight of a surfactant.

8. A composite composition of anti-plant virus agents, comprising the thiazolyl piperidine derivative according to claim 1 and other commercial fungicides as active ingredients; the ratio of the thiazolyl piperidine derivative and the other commercial anti-plant virus agents is 1%:99% to 99%:1% by weight, and the composite composition comprises 1% to 99% by weight of the active ingredient, 99% to 1% by weight of a solid or liquid adjuvant, and 0 to 25% by weight of a surfactant.

9. A plant immune activator compound composition, comprising the thiazolopiperidine derivative according to claim 1 and other commercial fungicides as active ingredients; the ratio of the thiazolopiperidine derivative to the other commercial plant immune activator is 1%:99% to 99%:1% by weight, and the compound composition comprises 1% to 99% by weight of the active ingredient, 99% to 1% by weight of a solid or liquid adjuvant, and 0 to 25% by weight of a surfactant.

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