CN108864075B - Isothiazole bithiazole derivative and preparation method and application thereof - Google Patents

Abstract

The invention provides isothiazole bithiazole derivatives, a preparation method and application thereof, and relates to isothiazole bithiazole compounds, which have a chemical structure general formula shown in formula V:

Description

Isothiazole bithiazole derivative and preparation method and application thereof

Technical Field

The technical scheme of the invention relates to N-containing S-containing isothiazole bithiazole derivatives, in particular to 3, 4-dichloroisothiazole bithiazole compounds.

Background

Heterocyclic compounds are used as effective active structures of a plurality of medicines, are widely used for the creation research of new pesticides, and enable modern pesticides to enter a new green and efficient stage. In recent years, most of heterocyclic compounds have been developed as N-containing heterocycles, and pyridine, pyrazole, imidazole, pyrimidine, triazole, thiazole, and fused heterocycle are mainly used (liu chang. world pesticides, chemical industry press, 2012). In 1962, thiazole compounds became the focus of agricultural chemicals research after the successful development of the fungicide thiabendazole (Thiabendazole) (Brown H D, Matzuk A R, Ilves I R, et al. Antiparatactic drugs. IV.2- (4-Thiazolyl) azimidazole, a new insecticidal [ J ]. Journal of the American Chemical Society, 1961, 83). In 2007, DuPont newly developed a piperidyl thiazole isoxazolide fungicide Oxathiapiprolin (paster, et al. Fungicide amides, WO 2008091580A 2) with excellent control effect on diseases of potatoes, grapes, vegetables and other characteristic crops. Oxathiapiprolin is a fungicide with good biological activity on oomycetes, particularly has special effect on downy mildew, but has a medium and high level of resistance risk due to single action site. In 1956 Adams and Slack reported for the first time and synthesized isothiazole rings by benzisothiazole (Adams A, Slack R. isothiazolazole: A new monnulear heterocyclic system [ J ]. Journal of the Chemical Society, 1959: 3061-: benziothiazolinone (benziothiazolinone), probenazole (oryzamate) and isotianil (isotianil). Isotianil is an isothiazole fungicide with resistance-inducing effect developed by bayer corporation in 1999 (Assmann, Lutz, et al, preparation of isothiazolecarboxamides as plants protectants, WO9924413 a2), which not only has strong biological activity against fungi, such as rhizomatous bacteria, oomycetes, chytrid, ascomycetes, etc., but also has a certain poisoning effect against insects (xiao yan, wangsun, huangjie, etc.. the novel fungicide isotianil [ J ] chinese pesticide, 2012 (1): 31-34.), in particular, the active sub-structure 3, 4-dichloroisothiazole has plant growth regulating effect (Chen l., synthesis, and fungal activity of 3, 4-dichloroisothiazole, rsc.20151, 3145).

The invention utilizes the principle of pesticide molecular design to combine 3, 4-dichloroisothiazole and piperidyl thiazole, designs and synthesizes a series of new isothiazole bithiazole compounds, and carries out systematic biological activity screening so as to provide more high-efficiency and low-resistance risk candidate compounds for the creation of new pesticides.

Disclosure of Invention

The technical problem to be solved by the invention is as follows: provides a synthesis method of novel isothiazole bithiazole derivatives, provides a method for regulating and controlling the biological activity of agricultural, horticultural and sanitary pests and plant pathogens of forestry plants by using the compounds and measuring the biological activity, and also provides application of the compounds in the agricultural field, the horticultural field, the forestry field and the sanitary field.

The technical scheme adopted by the invention for solving the technical problem is as follows: the chemical structural general formula of the isothiazole bithiazole derivative with insecticidal activity, bactericidal activity, plant virus resistance activity and disease resistance activity induced by plants in the agricultural field, the horticultural field, the forestry field and the sanitary field is shown as formula V:

V：

r is selected from H, H HCl, tert-butyloxycarbonyl,

C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy, C2-C6 alkenyl, C2-C6 haloalkenyl, C2-C6 alkynyl, C2-C6 haloalkynyl, C3-C6 cycloalkyl, substituted morpholin-1-yl, substituted tetrahydropyrrole-1-yl, phenyl, or halogen-substituted phenyl, or C1-C6 alkyl-substituted phenyl or C1-C6 haloalkyl-substituted phenyl or C3-C6 cycloalkyl-substituted phenyl, or nitro-substituted phenyl, or C2-C6 alkenyl-substituted phenyl, or C2-C6 haloalkenyl-substituted phenyl, or C6-C6 cycloalkenyl-substituted phenyl, or C6-C6 haloalkynyl-substituted phenyl, or C6-C6 cycloalkynyl-substituted phenyl, Pyridyl, or halogen substituted pyridyl, or C1-C6 alkyl substituted pyridyl, or C1-C6 haloalkyl substituted pyridyl, or C3-C6 cycloalkyl-substituted pyridyl, or nitro-substituted pyridyl, or C2-C6 alkenyl-substituted pyridyl, or C2-C6 haloalkenyl-substituted pyridyl, or C3-C6 cycloalkenyl-substituted pyridyl, or C6-C6 alkynyl-substituted pyridyl, or C6-C6 haloalkynyl-substituted pyridyl, or C6-C6 cycloalkynyl-substituted pyridyl, pyrimidinyl, or halogen-substituted pyrimidinyl, or C6-C6 alkyl-substituted pyrimidinyl, or C6-C6 haloalkyl-substituted pyrimidinyl, or C6-C6 cycloalkyl-substituted pyrimidinyl, or nitro-substituted pyrimidinyl, or C6-C6 alkenyl-substituted pyrimidinyl, or C6-C6 haloalkenyl-substituted pyrimidinyl, or C6-C6 cycloalkenyl-substituted pyrimidinyl, or C6-C6 alkynyl-substituted pyrimidinyl, or C6-C6 haloalkynyl-substituted pyrimidinyl, or C6-C6 cycloalkynyl-C6, A substituted five-or six-membered heteroaryl group containing 1 or 2N atoms, a substituted five-or six-membered heteroaryl group containing 1 or 2S atoms, a substituted five-or six-membered heteroaryl group containing 1 or 2O atoms, a substituted five-or six-membered heteroaryl group containing 1N atom and 1S atom, a substituted five-or six-membered heteroaryl group containing 1N atom and 1O atom, a substituted five-or six-membered heteroaryl group containing 2N atoms and 1S atom, a substituted five-or six-membered heteroaryl group containing 2N atoms and 1O atom; the five-or six-membered heteroaryl group is selected from: substituted furyl, thienyl, pyrrolyl, imidazolyl, pyrazolyl, thiazolyl, isothiazolyl, oxazolyl, isoxazolyl, oxadiazolyl, thiadiazolyl, pyridyl, pyridazinyl, pyrimidinyl, pyrazinyl, triazinyl, tetrazinyl, indolyl, benzothienyl, benzofuranyl, benzimidazolyl, indazolyl, benzotriazolyl, benzothiazolyl, benzothiadiazolyl, benzoxazolyl, isomerized quinolinyl, isomerized isoquinolinyl, phthalazinyl, quinoxalinyl, quinazolinyl, cinnolinyl or naphthyridinyl, alkyl-or alkenyl-substituted silicon groups;

wherein R is selected from H, phenyl, or halogen substituted phenyl, or C1-C6 alkyl substituted phenyl, or C1-C6 haloalkyl substituted phenyl, or C3-C6 cycloalkyl substituted phenyl, or nitro substituted phenyl, or C2-C6 alkenyl substituted phenyl, or C2-C6 haloalkenyl substituted phenyl, or C3-C6 cycloalkenyl substituted phenyl, or C2-C6 alkynyl substituted phenyl, or C2-C6 haloalkynyl substituted phenyl, or C3-C6 cycloalkynyl substituted phenyl, pyridyl, or halogen substituted pyridyl, or C1-C6 alkyl substituted pyridyl, or C1-C6 haloalkyl substituted pyridyl, or C3-C6 cycloalkyl substituted pyridyl, or nitro substituted pyridyl, or C2-C6 alkenyl substituted pyridyl, or C2-C6 haloalkenyl substituted pyridyl, Or C3-C6 cycloalkenyl-substituted pyridyl, or C2-C6 alkynyl-substituted pyridyl, or C2-C6 haloalkynyl-substituted pyridyl, or C3-C6 cycloalkynyl-substituted pyridyl, pyrimidinyl, or halogen-substituted pyrimidinyl, or C1-C6 alkyl-substituted pyrimidinyl, or C1-C6 haloalkyl-substituted pyrimidinyl, or C3-C6 cycloalkyl-substituted pyrimidinyl, or nitro-substituted pyrimidinyl, or C2-C6 alkenyl-substituted pyrimidinyl, or C2-C6 haloalkenyl-substituted pyrimidinyl, or C3-C6 cycloalkenyl-substituted pyrimidinyl, or C2-C6 alkynyl-substituted pyrimidinyl, or C2-C6 haloalkynyl-substituted pyrimidinyl, or C3-C6 cycloalkynyl-substituted pyrimidinyl, pyrazolyl, or halogen-substituted pyrazolyl, or C1-C6 alkyl-substituted pyrazolyl, Or C1-C6 haloalkyl-substituted pyrazolyl, or C3-C6 cycloalkyl-substituted pyrazolyl, or nitro-substituted pyrazolyl, or C2-C6 alkenyl-substituted pyrazolyl, or C2-C6 haloalkenyl-substituted pyrazolyl, or C3-C6 cycloalkenyl-substituted pyrazolyl, or C2-C6 alkynyl-substituted pyrazolyl or C2-C6 haloalkynyl-substituted pyrazolyl or C3-C6 cycloalkynyl-substituted pyrazolyl, or halogen-substituted pyrazolyl, or C6-C6 alkyl-substituted pyrazolyl, or C6-C6 haloalkyl-substituted pyrazolyl, or C6-C6 cycloalkyl-substituted pyrazolyl, or nitro-substituted pyrazolyl, or C6-C6 alkenyl-substituted pyrazolyl, or C6-C6 haloalkenyl-substituted pyrazolyl, or C6-C6 cycloalkenyl-substituted pyrazolyl, Or C2-C6 alkynyl-substituted pyrazolyl or C2-C6 haloalkynyl-substituted pyrazolyl or C3-C6 cycloalkynyl-substituted pyrazolyl, substituted five-or six-membered heteroaryl group having 1 or 2N atoms, substituted five-or six-membered heteroaryl group having 1 or 2S atoms, substituted five-or six-membered heteroaryl group having 1 or 2O atoms, five-or six-membered substituted heteroaryl group having 1N atom and 1S atom, substituted five-or six-membered heteroaryl group having 1N atom and 1O atom, substituted five-or six-membered heteroaryl group having 2N atoms and 1S atom, substituted five-or six-membered heteroaryl group having 2N atoms and 1O atom; the five-or six-membered heteroaryl group is selected from: substituted furyl, thienyl, pyrrolyl, imidazolyl, thiazolyl, isothiazolyl, oxazolyl, isoxazolyl, oxadiazolyl, thiadiazolyl, pyridyl, pyridazinyl, pyrimidinyl, pyrazinyl, triazinyl, tetrazinyl, indolyl, benzothienyl, benzofuranyl, benzimidazolyl, indazolyl, benzotriazolyl, benzothiazolyl, benzothiadiazolyl, benzoxazolyl, isomerized quinolinyl, isomerized isoquinolinyl, phthalazinyl, quinoxalinyl, quinazolinyl, cinnolinyl or naphthyridinyl, alkyl-or alkenyl-substituted silicon groups.

Halogen in the above definitions is fluorine, chlorine, bromine or iodine;

the alkyl, alkenyl or alkynyl is a linear or branched alkyl; alkyl is selected by itself or as part of another substituent from methyl, ethyl, propyl, butyl, pentyl, hexyl and isomers thereof selected from isopropyl, isobutyl, sec-butyl, tert-butyl, isopentyl or tert-pentyl;

the haloalkyl group is selected from the group consisting of one or more of the same or different halogen atoms, and the haloalkyl group is selected from CH₂Cl、CHCl₂、CCl₃、CH₂F、CHF₂、CF₃、CF₃CH₂、CH₃CF₂、CF₃CF₂Or CCl₃CCl₂；

The cycloalkyl group is selected by itself or as part of another substituent from cyclopropyl, cyclobutyl, cyclopentyl or cyclohexyl;

the alkenyl group is selected as such or as part of another substituent from vinyl, allyl, 1-propenyl, buten-2-yl, buten-3-yl, penten-1-yl, penten-3-yl, hexen-1-yl or 4-methyl-3-pentenyl;

the alkynyl group is selected by itself or as part of another substituent from ethynyl, propyn-1-yl, propyn-2-yl, butyn-1-yl, butyn-2-yl, 1-methyl-2-butynyl, hexyn-1-yl or 1-ethyl-2-butynyl.

The synthesis method of the isothiazole bithiazole derivative V comprises the following steps:

wherein, the substituent R is defined as the above, when the thiazole ring substitutes H at the 4-position of piperidine, the structure of V is shown as the following V-1:

wherein the substituent R is as defined above;

r is preferably selected from the group consisting of H, H HCl, t-butyloxycarbonyl, benzoyl, cyclohexanoyl, cyclopropylformyl, phenylacetyl, 3-fluoroacetoyl, cyclopropylacetyl, 4-fluorobenzoyl, 3-fluorobenzoyl, 2, 6-difluorobenzoyl, 4-chlorobenzoyl, 2, 4-dichlorobenzoyl, 3-chlorobenzoyl, 4-bromobenzoyl, 3-trifluoromethylbenzoyl, 4-methoxybenzoyl, 4-methylbenzoyl, 4-cyanobenzoyl, 1-R¹-5-trifluoromethyl-1H-pyrazole-4-formyl, 5-chloro-1-R²-3-trifluoromethyl-1H-pyrazole-4-formyl, 5- (difluoromethyl) -1-R³-1H-pyrazole-4-formyl, 3- (difluoromethyl) -1-methyl-1H-pyrazole-4-formyl, 1-methylpyrazole-4-formyl, (3, 5-dimethylpyrazol-1-yl) -1-acetyl, 3-trifluoromethyl-5-methyl-1-pyrazoleacetyl, 3-bromo-1- (3-chloro-2-pyridinyl) -1H-pyrazole-5-formyl.

R is as defined above¹Selected from phenyl, 4-fluorophenyl, 4-chlorophenyl, 4-bromophenyl, 4-trifluoromethylphenyl, 2, 4-dichlorophenyl, 3-fluorophenyl; r²Selected from phenyl, 4-fluorophenyl, 4-chlorophenyl, 4-bromophenyl, 4-trifluoromethylphenyl; r³Is selected from phenyl, 4-fluorophenyl, 4-chlorophenyl, 4-bromophenyl, 2, 4-dichlorophenyl.

When the thiazole ring substitutes H at the 3-position of piperidine, the structure of V is shown as V-2 below:

wherein the substituent R is as defined above;

r is selected from: t-butoxycarbonyl, H, acetyl, vinylformyl, benzoyl, 3-fluorobenzoyl, 3-trifluoromethylbenzoyl, 3-methoxybenzoyl, 3-nitrobenzoyl, 3-chlorobenzoyl, 3-methylbenzoyl, 3-bromobenzoyl.

The compound V can be prepared by condensation of an acid and an amine, depending on the starting materials for the reaction of the carbonyl-containing compound.

The specific method for synthesizing the target compound and measuring the biological activity comprises the following steps:

A. preparation of intermediate III:

adding 0.27 g of intermediate I into a 50 ml single-neck round-bottom flask, dissolving with 15 ml of tetrahydrofuran, adding 0.267 g of intermediate II into a reaction system, carrying out reflux reaction for 3 hours, filtering after the reaction is finished, obtaining filtrate and filter residue, wherein the filter residue is intermediate IV (yield: 16% -24%), removing the solvent from the filtrate through rotary evaporation, dissolving the filtrate with ethyl acetate, washing the filtrate with 1 mol/L NaOH solution, washing the filtrate with saturated sodium chloride, drying with anhydrous sodium sulfate, carrying out suction filtration, removing the solvent through rotary evaporation, purifying the residue through 200-300-mesh silica gel column chromatography to obtain intermediate III, wherein the eluent is ethyl acetate/60-90 ℃ fraction petroleum ether which is 1/15, and the yield is 46% -49% calculated by using the obtained pure product. The amount of intermediate III prepared and the volume of the reaction vessel are enlarged or reduced according to the corresponding proportion. The chemical structure and physicochemical parameters of intermediate III are shown in Table 1.

B. Preparation of intermediate IV:

putting 0.19 g of intermediate III into a 50 ml double-mouth round-bottom flask, adding 5 ml of anhydrous dichloromethane under the protection of nitrogen to dissolve, dropwise adding 1 ml of trifluoroacetic acid into a reaction bottle under the ice bath condition, reacting at room temperature for 2 hours, after the reaction is finished, adding 1 mol/L of sodium hydroxide solution under the ice bath condition to adjust the pH value to 8, separating an organic layer, back-extracting an aqueous layer once by using 20 ml of dichloromethane, collecting the organic layer, combining the organic layers, washing the organic layer once by using saturated sodium chloride, drying the anhydrous sodium sulfate, performing suction filtration, and removing the solvent by rotary evaporation to obtain an intermediate IV, wherein the yield is 90.5%, and the preparation amount of the intermediate IV and the volume of a reaction container are enlarged or reduced according to corresponding proportion. The chemical structure and physicochemical parameters of intermediate IV are shown in Table 1.

C. Preparation of isothiazolidinothiazole derivative V:

when R is H.HCl, the corresponding hydrochloride salt V of the compound is synthesized by the following method:

adding 0.12 g of compound IV into a 50 ml single-neck round-bottom flask, dissolving the compound IV by 10 ml of anhydrous methanol, stirring the mixture at room temperature, adding an excessive 4 mol/L dioxane solution of hydrogen chloride into the reaction, continuously stirring the mixture at room temperature for 3 hours, directly concentrating the reaction solution after the reaction is finished to remove an organic solvent, adding a proper amount of anhydrous ethanol into the flask, continuously concentrating the mixture to remove a small amount of water, and finally obtaining a white solid product V with the yield of 100%; the preparation amount of the compound V and the volume of the reaction vessel are enlarged or reduced according to corresponding proportion; the chemical structure and the physicochemical parameters of compound V are shown in Table 1.

When R is carbonyl compound, the method for synthesizing the corresponding hydrochloride V of the compound is as follows:

adding 0.49 mmol of carboxylic acid, 0.56 mmol of 1- (3-dimethylaminopropyl) -3-ethylcarbodiimide hydrochloride and 0.49 mmol of 1-hydroxybenzotriazole into a 50 ml double-neck round-bottom flask in turn, adding 10 ml of dried dichloromethane under ice bath condition for dissolving under nitrogen protection, removing the ice bath after 5 minutes of ice bath, stirring at room temperature for 1 hour, then adding 0.47 mmol of dichloromethane solution of intermediate IV under ice bath condition, finally adding 0.56 mmol of triethylamine, stirring at room temperature overnight, after reaction, adding 10 ml of water into the reaction system, separating an organic layer, washing the organic layer with saturated sodium bicarbonate and saturated sodium chloride in turn, drying with anhydrous sodium sulfate, carrying out suction filtration, rotationally evaporating to remove the solvent, purifying the residue by 200-300-mesh silica gel column chromatography to obtain an intermediate V, wherein the eluent is ethyl acetate/60-90 ℃ fraction petroleum ether (1/16-1/1), the yield is calculated by using the obtained pure product, and the yield is 59-100%. The amount of intermediate V prepared and the volume of the reaction vessel are enlarged or reduced according to the corresponding proportion. The chemical structure and physicochemical parameters of intermediate V are shown in Table 1.

D. The bactericidal activity of the isothiazole bithiazole derivative V of the invention is determined as follows:

the bactericidal or bacteriostatic activity of the isothiazole bithiazole derivative V adopts a thallus growth rate measuring method, and the specific steps are as follows: dissolving 1.8 mg of sample in proper amount of dimethylformamide, diluting with a water solution containing a certain amount of Tween 20 emulsifier to 500 microgram/ml of medicament, sucking 1 ml of the test medicament under an aseptic condition, injecting into a culture dish, adding 9 ml of PDA culture medium, shaking uniformly to prepare a 50 microgram/ml medicament-containing flat plate, taking the flat plate added with 1 ml of sterile water as a blank control, cutting a bacteria plate along the outer edge of hyphae by using a puncher with the diameter of 4 mm, transferring onto the medicament-containing flat plate, placing in an equilateral triangle, repeating the treatment for 3 times, placing the culture dish in a constant temperature culture box at 24 +/-1 ℃ for culture, investigating the expansion diameter of each treated bacteria plate after the diameter of the control bacterial colony is expanded to 2-3 cm, calculating the relative bacteriostasis rate by comparing with the blank control, wherein the test strain is the species of most typical plant pathogenic bacteria actually generated in the field in agricultural production in China, the code numbers and names are as follows: BC: the cucumber botrytis cinerea with the latin name as follows: botrytis cinerea, CA: peanut brown spot pathogen, its latin name is: cercospora arachidicola, GZ: wheat scab, its latin name is: gibberella zeae, PI: the late blight of potato, its latin name is: phytophthora infestans (Mont.) de Bary, PP: apple ring rot, its latin name is: physiosporia piricola, PS: rhizoctonia solani, the Latin name of which is: pellicularia sasakii, RC: rhizoctonia cerealis, with the latin name: rhizoctonia cerealis, SS: sclerotinia sclerotiorum, its latin name is: sclerotina sclerotiorum.

E. The isothiazole bithiazole derivative V and the intermediate thereof have the in-vivo bactericidal activity

Determination of the in vivo bactericidal activity of isothiazole bithiazole derivative V and its intermediates, the fungus tested was selected as typified by cucumber downy mildew latin, which is known under the name of (Pseudoperonospora cubensis (berk. et cut.) rosov, abbreviated as PCB). The specific test method is as follows: 0.01 g of the compound was weighed into 0.5 ml of DMF and diluted to the test concentration by adding aqueous solution (containing 1% Tween 80). The test liquid medicine is sprayed on the plants, the plants are dried for 2 hours, corresponding colonies are inoculated on the plants after 24 hours, mixed liquor of acetone, methanol and water (containing 1 percent Tween 80) in a volume ratio of 1: 2 is sprayed on each test to serve as blank control, the inhibition percentage of germs is calculated by comparing with the blank control, and the disease grading is carried out between the condition that the germs are completely inhibited by 100 and the condition that the germs are not inhibited by 0. The commercial fungicide fluorothiazole pyrithylone served as a positive control.

F. The activity of the isothiazole bithiazole derivative V and the intermediate thereof for resisting the tobacco mosaic virus is determined as follows:

the treatment mode is as follows:

the screening method of the anti-TMV therapeutic activity of the isothiazole bithiazole derivative V and the intermediate thereof comprises the following steps: adopting a living body friction inoculation method, carrying out friction inoculation on common tobacco seedlings with consistent seedling ages by carborundum on the 1 st day to obtain TMV, brushing medicine on the 3 rd day, and treating the following steps: the test compound solution is used for 2 to 3 times, 10 milliliters each time, the determination concentration is 100 micrograms/milliliter, the disease condition is checked on the 7 th day, the treatment antiviral effect of the test compound on TMV is calculated according to the following formula by integrating the number of disease spots, each treatment is repeated for 3 times, and water, ribavirin, BTH, TDL, ningnanmycin and the lead compound are respectively adopted as a blank control and a standard medicament control; the treatment effect was calculated from the examination results after 7 days:

wherein R is the antiviral therapeutic effect of the test compound on TMV in units: percent; CK is the average number of scorched spots of the clear water control leaf, unit: a plurality of; i is the average number of leaf blight after treatment with test compound, units: a plurality of;

protection mode:

the screening method of the anti-TMV protective activity of the isothiazole bithiazole derivative V and the intermediate thereof comprises the following steps: adopting a living body friction inoculation method, brushing medicine on the 1 st day and carrying out friction inoculation on TMV on the 3 rd day by carborundum on common tobacco seedlings with consistent seedling ages, wherein the treatment method comprises the following steps: the test compound solution is brushed for 2 to 3 times, 10 milliliters each time, the determination concentration is 100 micrograms/milliliter, the disease condition is checked on the 7 th day, the protective antiviral effect of the test compound on TMV is calculated according to the following formula by integrating the number of disease spots, each treatment is repeated for 3 times, and water, ribavirin, BTH, TDL, ningnanmycin and the lead compound are respectively selected as a blank control and a standard medicament control.

Wherein, R is the antiviral protection effect of the test compound on TMV, and the unit is: percent; CK is the average number of scorched spots of the clear water control leaf, unit: a plurality of; i is the average number of scorched spots of the leaves after the test compound protection treatment, unit: a plurality of;

passivation mode:

the screening method of the anti-TMV inactivation activity of the isothiazole bithiazole derivative V and the intermediate thereof comprises the following steps: a living body rubbing inoculation method is adopted, a new compound, a target compound and TMV are mixed for about 5 hours, common tobacco seedlings with the same seedling age are selected, 10 ml of mixed liquid of the target compound and the TMV and carborundum are used for rubbing inoculation to dip-dye tobacco leaves for 3 pieces, the concentration of a test compound in the mixed liquid is 100 micrograms/ml, the disease occurrence condition is checked on the 7 th day, the passivation antiviral effect of the test compound on the TMV is calculated according to the following formula by integrating the number of dead spots, each treatment is repeated for 3 times, and water, ribavirin, BTH, TDL, ningnanmycin and the lead compound of the invention are respectively selected as a blank control and a standard medicament control.

Wherein, R is the antiviral inactivation effect of the test compound TMV, and the unit is: percent; CK is the average number of scorched spots of the clear water control leaf, unit: a plurality of; i is the average number of scorched spots of the leaves after passivation with the test compound, unit: a plurality of;

induction mode:

the screening method of the anti-TMV induction activity of the isothiazole bithiazole derivative V and the intermediate thereof comprises the following steps: the living body is measured by a leaf soaking method, common tobacco seedlings with consistent seedling ages are brushed with medicines on day 1, medicines on day 3 and medicines on day 5, and viruses are grafted on newly grown leaves on day 7, and the treatment method is as follows: the test compound solution is tested 2 to 3 times, 10 milliliters each time, the determination concentration is 100 micrograms/milliliter, the disease condition is checked after 7 days of virus inoculation, the induced antiviral effect of the test compound on TMV is calculated according to the following formula by integrating the number of disease spots, each treatment is repeated for 3 times, and the blank control and the standard medicament control are respectively selected from water, ribavirin, BTH, TDL, ningnanmycin and the lead compound of the invention.

Wherein, R is the induction effect of the test compound on the TMV resistance of the tobacco, and the unit is as follows: percent; CK is the average number of scorched spots of the clear water control leaf, unit: a plurality of; i is the average number of scorched spots of the leaves after the induction treatment with the test compound, unit: and (4) respectively.

G. The isothiazole bithiazole derivative V and the intermediate thereof have the following insecticidal activity to armyworm:

the isothiazole bithiazole derivative V and the intermediate thereof have insecticidal activity on armyworms screened by a leaf soaking method: weighing 2 mg of medicine sample on an analytical balance, putting the medicine sample in a 10 ml penicillin glass bottle, adding 10 ml acetone to obtain a mother solution of 100 micrograms/ml, covering a rubber plug to vibrate and dissolve, then diluting the medicine solution into a working solution of 5 micrograms/ml by using acetone, dipping the corn leaves by using straight-head ophthalmic tweezers for 2-3 seconds, and throwing off residual liquid; 1 tablet at a time, 8 tablets per sample; sequentially placing the samples on processing paper according to the sample marking sequence, placing the samples into a culture dish with 10 cm marks after liquid medicine is dried, using an elbow ophthalmic forceps to insert 10 heads of 3-year-old primary armyworm larvae, placing the test treatment in a constant-temperature standard insect culturing room to culture for 72 hours, and then checking the result, using a small brush pen or the forceps to lightly touch the larva bodies, and using the fact that the larvae are completely immobile as the death standard; corn leaves impregnated with acetone solution were blank.

The invention has the beneficial effects that: the isothiazole bithiazole derivative V is subjected to lead optimization, and the synthesized new compound is subjected to screening of insecticidal activity, bacteriostatic activity and antiviral activity.

The synthesis, biological activity and application of isothiazole bithiazole derivative V are more specifically illustrated by specific preparation and biological activity determination examples, which are only used for specifically illustrating the invention and not limiting the invention, and particularly, the biological activity is only illustrated but not limiting the patent, and the specific embodiments are as follows:

example 1: preparation of intermediate III-1:

adding 0.27 g of intermediate I into a 50 ml single-neck round-bottom flask, dissolving with 15 ml of tetrahydrofuran, adding 0.267 g of intermediate II N-Boc-piperidine-4-thiocarbamide into a reaction system, carrying out reflux reaction for 3 hours, filtering after the reaction is finished, obtaining filtrate and filter residue, wherein the filter residue is intermediate IV-1 (yield: 16%), removing the solvent from the filtrate through rotary evaporation, dissolving with ethyl acetate, washing with 1 mol/L NaOH solution, washing with saturated sodium chloride, drying with anhydrous sodium sulfate, carrying out suction filtration, removing the solvent through rotary evaporation, purifying the residue through 200-300-mesh silica gel column chromatography to obtain intermediate III-1, wherein the eluent is ethyl acetate/60-90 ℃ fraction petroleum ether 1/15, and the yield is 46% calculated by using the obtained pure product.¹H NMR(400MHz，CDCl3)δ8.04(s，1H)，4.34-4.10(m，2H)，3.19(m，1H)，2.93(t，J＝12.1Hz，2H)，2.13(t J＝12.7Hz，2H)，1.87-1.66(m，3H)，1.46(d，J＝22.8Hz，9H).¹³C NMR(101MHz，CDCl3)δ175.31(s)，155.10(s)，154.66(s)，148.73(s)，143.35(s)，116.74(s)，79.75(s)，43.40(s)，40.38(s)，32.19(s)，28.44(s).

Example 2: preparation of intermediate VII-2:

adding 0.1 g of compound I into a 50 ml single-neck round-bottom flask, dissolving with 15 ml of tetrahydrofuran, adding 0.09 g of an intermediate II-2N-Boc-piperidine-3-thiocarbamide into a reaction system, carrying out reflux reaction for 3 hours, filtering after the reaction is finished to obtain a filtrate and a filter residue, wherein the filter residue is an intermediate IV-2 (yield: 24%), removing the solvent from the filtrate through rotary evaporation, dissolving with ethyl acetate, washing with 1 mol/L NaOH solution, washing with saturated sodium chloride, drying with anhydrous sodium sulfate, carrying out suction filtration, removing the solvent through rotary evaporation, purifying the residue through 200-300-mesh silica gel column chromatography to obtain an intermediate III-2, and using ethyl acetate as an eluent/60-90 ℃ fraction petroleum ether as 1/15, and calculating the yield of the obtained pure product to be 49%. 1H NMR (400MHz, CDCl 3). delta.8.07 (s, 1H), 4.32(m, 1H), 4.00(d, 1H), 3.22(m, 1H), 2.98(m, 1H), 2.25(d, 1H), 1.83(m, 2H), 1.74-1.58(m, 2H), 1.49(s, 9H), 1.36-1.20(m, 1H).

Example 3: preparation of intermediate VIII-1:

placing 0.19 g of intermediate III-1 into a 50 ml double-mouth round-bottom flask, adding 5 ml of anhydrous dichloromethane under the protection of nitrogen to dissolve, dropwise adding 1 ml of trifluoroacetic acid into a reaction bottle under the ice bath condition, reacting at room temperature for 2 hours, after the reaction is finished, adding 1 mol/L sodium hydroxide solution under the ice bath condition to adjust the pH value to 8, separating an organic layer, performing back extraction on an aqueous layer by using 20 ml of dichloromethane once, collecting the organic layer, combining the organic layers, washing the organic layer once by using saturated sodium chloride, drying the anhydrous sodium sulfate, performing suction filtration, and removing the solvent by rotary evaporation to obtain an intermediate IV-1, wherein the yield is calculated by using the obtained pure product and is 90.5%.¹H NMR(400MHz，CDCl3)δ8.04(s，1H)，5.31(s，1H)，3.33-3.11(m，3H)，2.78(t，J＝11.7Hz，2H)，2.14(t，J＝11.9Hz，2H)，1.76(m，2H).¹³C NMR(101MHz，CDCl3)δ176.51(s)，155.26(s)，148.73(s)，143.20(s)，116.66(s)，46.25(s)，40.86(s)，33.66(s).

Example 4: preparation of isothiazolidinepiperidine derivative Wqf-2 when R1 is H · HCl:

adding 0.12 g of compound IV-1 into a 50 ml single-neck round-bottom flask, dissolving the compound IV-1 by 10 ml of anhydrous methanol, stirring the mixture at room temperature, adding an excessive 4 mol/L dioxane solution of hydrogen chloride into the reaction, continuously stirring the mixture at room temperature for 3 hours, directly concentrating the reaction solution after the reaction is finished to remove an organic solvent, adding a proper amount of anhydrous ethanol into the flask, continuously concentrating the mixture to remove a small amount of water to finally obtain a white solid product wqf-2, and calculating the yield by using the obtained pure product, wherein the yield is 100%.¹H NMR(400MHz，DMSO)δ9.54(s，1H)，9.32(s，1H)，8.50(d，J＝16.0Hz，1H)，3.35(m，2H)，3.05(m，2H)，2.53(d，J＝14.0Hz，1H)，2.24(s，2H)，2.04(t，J＝11.8Hz，2H).¹³C NMR(101MHz，DMSO)δ175.30(s)，155.55(s)，148.38(s)，142.10(s)，120.05(s)，42.85(s)，37.28(s)，28.76(s).

Example 5: when R is₁Preparation of isothiazolidinepothiylpiperidine derivative Wqf-4 for benzoyl:

adding 0.04 g of benzoic acid, 0.072 g of 1- (3-dimethylaminopropyl) -3-ethylcarbodiimide hydrochloride and 0.044 g of 1-hydroxybenzotriazole into a 50 ml double-neck round-bottom flask in sequence under the protection of nitrogen, adding 10 ml of dry dichloromethane for dissolution under ice bath conditions, removing the ice bath after 5 minutes of ice bath, stirring for 1 hour at room temperature, adding 0.1 g of dichloromethane solution of intermediate IV-1 under ice bath conditions, and finally adding 0.038 g of triethyl phosphateAfter the reaction is completed, 10 ml of water is added into the reaction system, an organic layer is separated, the organic layer is washed by saturated sodium bicarbonate and saturated sodium chloride, dried by anhydrous sodium sulfate, filtered by suction, the solvent is removed by rotary evaporation, and the residue is purified by 200-300 mesh silica gel column chromatography to obtain a white solid Wqf-4, wherein the eluent is ethyl acetate/60-90 ℃ fraction petroleum ether (1/16-1/1), and the yield is 100%. 1H NMR (400MHz, CDCl3) delta 7.95(d, J ═ 5.4Hz, 1H), 7.34(d, J ═ 9.6Hz, 5H), 4.68(m, 1H), 3.81(m, 1H), 3.23(m, 1H), 3.04(t, J ═ 55.1Hz, 2H), 2.10(t, J ═ 47.2Hz, 2H), 1.74(m, 2H).¹³C NMR(101MHz，CDCl3)δ174.60(s)，170.57(s)，155.00(s)，148.72(s)，143.31(s)，135.78(s)，129.81(s)，128.57(s)，126.94(s)，117.00(s)，40.25(s)，32.12(s)，29.71(s).

Example 6: the result of the in vitro antibacterial activity determination of the piperidine thiazole derivative V of the invention 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, PI: the late blight of potato, its latin name is: phytophthora infestans (Mont.) de Bary, PP: apple ring rot, its latin name is: physiosporia piricola, PS: rhizoctonia solani, the Latin name of which is: pellicularia sasakii, RC: rhizoctonia cerealis, with the latin name: rhizoctonia cerealis, SS: sclerotinia sclerotiorum, its latin name is: sclerotina sclerotiorum, a species that can represent the majority of the pathogenic species occurring in the field in agricultural production. The results of the measurement of the growth rate of the thalli are shown in table 2, and the table 2 shows that all the compounds of the isothiazole bithiazole synthesized by the invention have bactericidal activity of different degrees at 50 micrograms/ml. For potato late blight, the inhibitory activity of the compounds Wqf1, Wqf2, Wqf16, Wqf17, Wqf18 and Wqf51 is more than 40%, and the inhibitory activity is higher than that of the lead compounds isotianil (the inhibitory rate of the compound to potato late blight is 26%) and OxathiThe apiprolan (the inhibition rate of the potato late blight is 16%) is more than 10%. The activity results on the cercospora arachidicola show that the inhibitory activity of compounds Wqf1, Wqf2, Wqf11, Wqf15, Wqf16, Wqf17, Wqf18, Wqf21, Wqf24, Wqf25, Wqf26, Wqf28, Wqf37, Wqf38, Wqf43 and Wqf46 is more than 45%, the activity is more than 10% higher than that of lead compounds isotianil (the inhibitory rate on the peanut brown spot is 17%) and Oxathiapiprolin (the inhibitory rate on the peanut brown spot is 32%), the activity of compounds Wqf11, Wqf2-21 and Wqf46 on the peanut brown spot is more than 70%, and the activity of compounds Wqf11 and Wqf46 on the peanut brown spot is more than 85%. The activity test result on the tomato early blight bacteria shows that the antibacterial activity of the compounds Wqf1, Wqf2, Wqf5, Wqf15, Wqf16, Wqf17, Wqf18, Wqf23, Wqf24, Wqf25, Wqf26, Wqf27, Wqf28, Wqf38, Wqf41, Wqf43, Wqf44, Wqf46, Wqf47, Wqf48, Wqf49 and Wqf52 is more than 35%, the antibacterial activity is more than 10% higher than that of the lead compounds isotianil (the inhibition rate on the tomato early blight is 23%) and Oxathiapiprolin (the inhibition rate on the tomato early blight is 10%), wherein the antibacterial activity of the compounds Wqf1, Wqf16, Wqf17, Wqf2-26, Wqf44 and Wqf46 is more than 60%, and the activity of the compound Wqf46 is the highest and is 86%. The activity test on cucumber gray mold bacteria shows that the bacteriostatic activity of Wqf1, Wqf2, Wqf16, Wqf29, Wqf31, Wqf32, Wqf33, Wqf34, Wqf35, Wqf36 and Wqf38 is more than 56 percent, the activity is higher than that of a lead compound isotianil (the inhibition rate on cucumber gray mold is 7 percent) and that of Oxathiapiprolin (the inhibition rate on cucumber gray mold is 56 percent), the bactericidal activity of the compounds Wqf1, Wqf16, Wqf29, Wqf32 and Wqf34 is more than 10 percent of that of the compound Oxathiapiprolin, and the inhibition rate of Wqf1 and Wqf29 on cucumber gray mold can reach more than 70 percent. The activity test on wheat scab bacteria shows that the bacteriostatic activity of the compounds Wqf1, Wqf11, Wqf15, Wqf16, Wqf17, Wqf18, Wqf23, Wqf25, Wqf26, Wqf27, Wqf38, Wqf43, Wqf44 and Wqf46 is more than 50%, the bactericidal activity of the compounds is more than 30% higher than that of the lead compound isotianil, wherein the bacteriostatic activity of the compound Wqf46 on wheat scab is the highest and is 94%. The activity test of the ring rot apple bacteria shows that the compounds Wqf1, Wqf2 and Wqf8. Wqf13, Wqf15, Wqf16, Wqf17, Wqf21, Wqf22, Wqf24, Wqf25, Wqf26, Wqf38, Wqf44 and Wqf52 have the antibacterial activity of more than 35 percent, the activity of the compound is higher than that of the lead compound isotianil (the inhibition rate of the compound to the apple ring spot is 24 percent) and that of Oxathiapiprolin (the inhibition rate of the compound to the apple ring spot is 16 percent), and the antibacterial activity of the compound Wqf1, Wqf17, Wqf25, Wqf2-26 and Wqf44 is higher than 60 percent. The activity test on sclerotinia sclerotiorum shows that the bacteriostatic activity of the compounds Wqf1, Wqf2, Wqf3, Wqf4, Wqf7, Wqf11, Wqf13, Wqf14, Wqf15, Wqf16, Wqf17, Wqf18, Wqf28, Wqf31, Wqf34, Wqf35, Wqf36, Wqf39, Wqf40, Wqf41, Wqf42, Wqf47, Wqf50 and Wqf51 is more than 60 percent, the activity is more than 15 percent of that of a lead compound isotianil (the inhibition rate on sclerotinia sclerotiorum disease is 45 percent), particularly, the inhibition rates of the compounds Wqf1, Wqf2, Wqf7, Wqf11 and Wqf13 on sclerotinia sclerotiorum disease are all 100 percent, and the activity is higher than that of the lead compound Oxathiapiprolin (the inhibition rate on sclerotiorum disease is 90 percent). The activity test on the rhizoctonia cerealis shows that the bacteriostatic activity of the compounds Wqf1, Wqf2, Wqf15, Wqf16, Wqf17, Wqf18, Wqf21, Wqf22, Wqf24, Wqf25, Wqf26, Wqf32, Wqf38, Wqf44, Wqf46, Wqf47, Wqf49 and Wqf53 is more than 30%, the activity of the compounds is more than 10% higher than that of the lead compounds isotianil (the inhibition rate on the rhizoctonia cerealis is 16%) and Oxathiapiprolin (the inhibition rate on the rhizoctonia cerealis is 20%), the inhibition rate of the compounds Wqf1, Wqf2, Wqf18 and Wqf25 on the rhizoctonia cerealis is more than 65%, and the inhibition rate of the compound Wqf1 on the rhizoctonia cerealis is 96%. The activity test of the compounds for rhizoctonia solani shows that the bacteriostatic activity of the compounds Wqf1, Wqf2, Wqf15, Wqf16, Wqf17, Wqf18, Wqf25, Wqf35, Wqf38 and Wqf44 is more than 35%, the activity of the compounds is higher than that of the lead compounds isotianil (the inhibition rate of the compounds for rhizoctonia cerealis is 22%) and Oxathiapiprolin (the inhibition rate of the compounds for rhizoctonia cerealis is 25%) and the inhibitory activity of the compounds Wqf1, Wqf2 and Wqf44 for rhizoctonia solani is more than 60%, wherein the inhibition rate of the compound Wqf1 for the rhizoctonia solani is 82%, and the invention further performs precise toxicity test result (EC) on the compounds with the bacteriostatic activity of more than 70 at 50 micrograms/ml (EC)₅₀Microgram of/ml), as shown in Table 3, for Fusarium oxysporum, compounds Wqf11 and Wqf21 had their EC against it₅₀The values are all below 25 microgram/ml, and the active bacteria are higher than a control compound Oxathiapiprolin (EC)₅₀: 79.20 μ g/ml), in particular compound Wqf11, which has EC against brown spot pathogen₅₀The value is only 5.57 micrograms/ml, and for tomato early blight bacteria, the compound Wqf44 has better inhibitory activity and EC₅₀The value can reach 8.92 micrograms/ml, and for botrytis cinerea, the EC of the compound Wqf1 for the botrytis cinerea is₅₀The value is 11.41 microgram/ml, which is 1/3 of the control drug Oxathiapiprolin, for Gibberella tritici, although the activity of the tested compounds is inferior to that of the control Oxathiapiprolin, the compounds Wqf13, Wqf44 and Wqf38 also show better bacteriostatic activity, EC₅₀The values are 15.03, 15.60 and 7.67. mu.g/ml respectively, and the inhibitory activity of the compound Wqf1 on Sclerotinia sclerotiorum is equivalent to that of the control drug Oxathiapiprolin, EC₅₀The values are all close to 6.00. mu.g/ml, and the EC of Wqf7, Wqf11 and Wqf13 is applied to the values₅₀All values are much lower than Oxathiapiprolin, in particular, EC of Compound Wqf11 against Sclerotinia sclerotiorum₅₀The value was 0.045. mu.g/ml, only the EC of Oxathiapiprolin for Sclerotinia sclerotiorum₅₀(5.98. mu.g/ml) 1/130 for Rhizoctonia cerealis, compound Wqf1 and Wqf2 for its EC₅₀Values were 15.60 and 7.67 μ g/ml, respectively. Therefore, the new compound designed and synthesized by the invention has obviously improved bactericidal activity of a target compound compared with that of a lead compound Oxathiapiprolin due to the difference of introduced substituent groups, which is a place for creatively distinguishing the invention from the prior invention.

To date, the inventors have designed the chemical structures and EC of several most active compounds among the synthesized thiazolopiperidine-containing compounds₅₀The results of the value measurements are shown in tables 4 and 5, and from table 4: the compounds have good inhibitory activity on Sclerotinia sclerotiorum, and the compound IIA-13 has good inhibitory activity on EC of Rhizoctonia Cerealis (RC)₅₀The value is 39.76 mug/mL, and the EC of the compounds VIA-17, VIA-19, VIA-23 and VIA-27 on Sclerotinia Sclerotiorum (SS)₅₀The values were 31.22. mu.g/mL, 30.58. mu.g/mL, 5.68. mu.g/mL, and 5.74. mu.g/mL, respectively.EC of compound VIB-13 on Botrytis Cinerea (BC)₅₀The value was 34.72. mu.g/mL. Compared with the results in the table 3, the bactericidal activity of the compound designed and formed by the invention is obviously better than that of the positive control compound Oxathiapiprolin and all other thiazolepiperidine high-activity compounds designed and synthesized by the subject group of the inventor. Therefore, the biological activity of the target compound is unexpectedly and remarkably improved due to the creative introduction of isothiazole into the target molecule and direct connection of isothiazole with a thiazole ring of the inventor, and the results of design synthesis and biological activity test of the compounds show that the compounds with novel structures have good creativity.

Example 7: insecticidal activity results of isothiazolidinothiazole derivative V of the present invention:

the results of the insecticidal activity assay of isothiazolyl bithiazole derivative V are shown in table 6, and table 6 shows: when the concentration of the test reagent is 100 micrograms/ml, after the observation effect is carried out for 72 hours, the lead compound Oxathiapiprolin has no toxic activity on cotton bollworms and corn borers, the toxic activity on armyworms is only 15 percent, the compound in the invention has certain toxic activity on armyworms, cotton bollworms and corn borers, the activity test on the armyworms shows that the toxic activity of the compounds Wqf14, Wqf28 and Wqf42 on the armyworms is more than 70 percent and more than 55 percent higher than that of the lead compound Oxathiapiprolin, the toxic activity of the compounds Wqf28 and Wqf42 on the armyworms is 100 percent at 100 micrograms/ml, which is equivalent to that of positive control ethiprolide, particularly, when the concentration is reduced to 50 micrograms/ml, the toxic activity of the ethiprolide on the armyworms is only 50 percent, while the toxic activity of the compound Wqf28 on the armyworms is still 100 percent, the activity test on the cotton bollworms shows that when the concentration of the test reagent is 100 micrograms/ml, the poisoning activity of the compounds Wqf28 and Wqf42 to cotton bollworm is more than 75 percent, which are both higher than that of lead compounds isotianil and Oxathiapiprolin, and is more than 55 percent higher than thiamethoxam, the poisoning activity of the compound Wqf42 to cotton bollworm is 75 percent, which is equivalent to positive control ethiprole, the poisoning activity of the compound Wqf28 to cotton bollworm is 100% when the concentration of the test reagent is 100 microgram/ml, which is 25% higher than that of positive control ethiprole, the activity test of the corn borer shows that when the concentration of the reagent is 100 micrograms/ml, the poisoning activity of the compounds Wqf28 and Wqf42 on corn borers is more than 45 percent, which are both higher than that of lead compounds isotianil and Oxathiapiprolin, and is more than 25 percent higher than thiamethoxam, the poisoning activity of the compound Wqf28 to corn borer is 100 percent and is 35 percent higher than that of positive control ethiprole, when the concentration is reduced to 50 micrograms/ml, the poisoning activity of the compound Wqf28 on the corn borer can reach 55%.

Example 8: the application of the piperidine thiazole derivative, agriculturally acceptable auxiliary agents and commercial insecticides in preparing compound insecticides comprises the following steps:

the piperidine thiazole derivative, an agriculturally acceptable auxiliary and one or more commercial insecticides are combined to prepare the compound insecticide. The commercial pesticide is selected from: chlorpyrifos, diazinon, acetamiprid, emamectin benzoate, milbemectin, abamectin, pleocidin, fenvalerate, cypermethrin, Lambda-cyhalothrin, cyfluthrin, deltamethrin, fenpropathrin, Beta-cyfluthrin, Lambda-cyhalothrin, permethrin, allethrin, cyfluthrin, bifenthrin, permethrin, ethrin, flumethrin, cyhalothrin, imidacloprid, acetamiprid, nitenpyram, imidacloprid, thiacloprid, thiamethoxam, dinotefuran, clothianidin, dinotefuran, diflubenzuron, chlorbenzuron, tefluazuron, flufenoxuron, lufenuron, toxflufenoxuron, Novaluron, novifu 1umuron, and its CAS 02, 3-121451-Novaluron, cyflufenoxuron, cyhalonil, cyhalothrin, cy, Chlorfluazuron, Bay SIR 6874 namely {1- [ (3.5-dichloro-4) 4-nitrophenoxyphenyl 3-3- (2-chlorobenzene) -urea }, Bay SIR-8514 namely [1- (4-trifluoromethoxyphenyl) -3- (2-chlorobenzene) -urea ], flufenoxuron, Bistrifulon namely Bistrifluron, fufenozide, tebufenozide, chlorfenapyr, methoxyfenozide, chromafenozide, dimethoate, omethoate, dichlorvos, acephate, triazophos, quinalphos, pyridaphenthion, chlorzofos, tetrafenox, pirimicarb, metolcarb, fenobucarb, proparacarb, carbosulfan, cartap, fenitrothion, fenisobromolate, hexythiazox, pyridaben, clofentezine, propargite, propargyl, Diafenthiuron, prothiocarb, pymetrozine, spirodiclofen, spirotetramat, butene-fipronil, azocyclotin, buprofezin, fenamiphos, fipronil, monosultap, dimehypo, chlorantraniliprole, flubendiamide, cyantraniliprole, tebufenpyrad, chlorfenapyr, pyrazinone, etoxazole, tebufenpyrad, pyridaben, pyriproxyfen, emamectin; the total mass percentage content of the piperidine thiazole derivative in the obtained compound insecticide is 1-90 percent, and the mass percentage of the piperidine thiazole derivative and the commercial insecticide is 1 percent to 99 percent to 1 percent; the formulation suitable for the compound pesticide is selected from a seed treatment emulsion, an aqueous emulsion, a large granule, a microemulsion, a suspoemulsion, a water soluble granule, a soluble concentrated agent, a water dispersible granule, a poison valley, an aerosol, a block poison bait, a slow release block, a concentrated poison bait, a capsule granule, a microcapsule suspension, a dry-mixed seed powder, a missible oil, an electrostatic spray, an aqueous oil-in-water emulsion, an oil-in-water emulsion, a smoke tank, a fine granule, a smoke candle, a smoke cylinder, a smoke rod, a seed treatment suspension, a smoke tablet, a smoke pill, a granular poison bait, an air forming agent, a drift powder, an ointment, a hot fogging agent, a solid/liquid mixed agent, a liquid/liquid mixed agent, a cold fogging agent, a solid/solid mixed agent, a medicinal paint, a fine granule, an oil suspension agent, an oil dispersible powder, a flaky poison bait, a concentrated gel agent, a pouring agent, a seed coating agent, a smearing agent, a small, Any one of soluble powder, seed treatment water soluble powder, ultra-low volume suspending agent, tracing powder, ultra-low volume liquid, steam releasing agent and wet-mixed seed water dispersible powder; the plant suitable for the compound pesticide is selected from rice, wheat, barley, oat, corn, sorghum, sweet potato, cassava, soybean, sweet broad bean, pea, mung bean, small bean, cotton, silkworm, peanut, rape, sesame, sunflower, beet, sugarcane, coffee, cocoa, ginseng, fritillaria, rubber, coconut, oil palm, sisal, tobacco, tomato, hot pepper, radish, cucumber, cabbage, celery, tuber mustard, beet, rape, shallot, garlic, watermelon, melon, cantaloupe, papaya, apple, orange, peach, tea, potherb, bamboo shoot, hop, pepper, banana, papaya, orchid, bonsai; the insect pest controlled by the compound pesticide is selected from east Asian planthopper, spruce car locust, Chinese rice locust, Japanese yellow locust, single-thorn mole cricket, oriental mole cricket, rice thrips, tobacco thrips, greenhouse thrips, rice straw thistle, wheat simple pipe thrips, greenhouse white fly, tobacco whitefly, black tail hopper, big leaf hopper, cotton leafhopper, leaf hopper, leaf spot cicada, brown plant hopper, white back plant hopper, gray plant hopper, sugarcane flat angle plant hopper, cotton aphid, binary wheat aphid, wheat straw aphid, peach aphid, sorghum aphid, radish aphid, mealybug, stinkbug, pear bug, white wax insect, red wax insect, fresh mealybug, pear net, banana net bug, tiny bugs, tiny flower fly bug, lacewing fly, rice-wing, brown spider, rice moth, black armyworm, black rice moth, black armyworm, black rice moth, black rice green fly, black rice plant hopper, green plant hopper, black rice plant, Wheat moth, pink bollworm, sweet potato moth, diamond back moth, peach fruit borer, soybean pod borer, peach fruit borer, apple tip leaf roller, brown banded leaf roller, pseudolariciresia pulvinata, striped rice borer, bean pod borer, corn borer, yellow rice borer, cabbage moth, rice leaf roller, striped rice borer, cotton leaf roller, peach borer, armyworm, prodenia litura, rice bollworm, cotton bollworm, beet armyworm, pink bollworm, diamond-point diamond-greenbrier, black tiger, yellow cutworm, pirate moth, gypsy moth, sweet potato hawkmoth, bean hawkmoth, straight-line butterfly, cryptophysalia leucopteris, butterfly, jade belt butterfly, cabbage pink butterfly, red butterfly ramie, ramie yellow cabbage caterpillar, yellow turnip lilac, yellow cabbage caterpillar, yellow beetle, gold beetle, yellow beetle, pink beetle, yellow beetle, pink beetle, yellow beetle, black, Mealworm, tribolium castaneum, Aerugo, Holotrichia diomphalia Bates, Monochamus aurantiaca, Monochamus orbiculatus, Monochamus wallichus, Calomelas flavus, Calomelas fir, pissodes radiata, Vibrio fabus, Zedoides zeae, Mimoset germars, Ceripomoea piricola, Brachyspiraea chalcogramma, Sciaenopsis invicta, Sciadoptera chrysosporium, Sciadoptera infantopus, Sciadoptera infanensis, Musca murella hui, Gekko luteo, Muscat, Musca lutea virens, Musca citri, Musca citrella hulus, Musca muris, Musca murella hui, Musca praecolus, Musca praeco.

Example 9: the application of the piperidine thiazole derivative, agriculturally acceptable auxiliary agents and commercial bactericides in preparing compound bactericides comprises the following steps:

the piperidine thiazole derivative disclosed by the invention is combined with an agriculturally acceptable auxiliary and one or more commercial bactericides to prepare a compound bactericide. The commercial bactericide is selected from diazosulfide, tiadinil, methidam, 4-methyl-1, 2, 3-thiadiazole-5-formic acid, 4-methyl-1, 2, 3-thiadiazole-5-sodium formate, 4-methyl-1, 2, 3-thiadiazole-5-ethyl formate, 4-bromomethyl-1, 2, 3-thiadiazole-5-ethyl formate, 4-iodomethyl-1, 2, 3-thiadiazole-5-ethyl formate, 4-bromomethyl-5-methyl-1, 2, 3-thiadiazole, 4-iodomethyl-5-methyl-1, 2, 3-thiadiazole and 4, 4-dibromomethyl-1, ethyl 2, 3-thiadiazole-5-carboxylate, 3, 4-dichloroisothiazole-5-carboxylic acid, sodium 3, 4-dichloroisothiazole-5-carboxylate, ethyl 3, 4-dichloroisothiazole-5-carboxylate, DL-beta-aminobutyric acid, isotianil, ribavirin, antofine, ningnanmycin, thiiramide, salicylic acid, pyriminomycin, dichloroisonicotinic acid, probenazole, cymoxanil, thiram, ziram, mancozeb, fosetyl-aluminium, thiophanate-methyl, chlorothalonil, chlorcoson, procymidone, fenpropidin, thiophanate-methyl, propamocarb-ethyl, salicylic acid, flumorph, dimethomorph, propamocarb-ethyl, diclocyanide, flusulfamide, thiflufenamid, flutolanilide, bisoprostol, cyprodin, cyprodinil, thifluzamide, thifluazid-methyl, Cyflufenamid, fenhexamid, cyamed, silthiopham, furametpyr, penthiopyrad, mandipropamid, zoxamide, difuramide, carboxin, ethiprole, iprodione, azoxystrobin, dimoxystrobin, kresoxim-methyl, metominostrobin, orysastrobin, picoxystrobin, pyraclostrobin, trifloxystrobin, enestroburin, dimethomoxamine, epoxiconazole, bromuconazole, cyproconazole, difenoconazole, diniconazole, epoxiconazole, fenbuconazole, fluquinconazole, flusilazole, flutriafol, hexaconazole, imibenconazole, ipconazole, metconazole, myclobutanil, penconazole, propiconazole, prothioconazole, simeconazole, tebuconazole, tetraconazole, triadimenol, triticonazole, thiabendazole, maifanin, imazalil, prochloraz, cycuronazole, cyazofamid, imazalil, cyazofamid, isoprozachlor, isoprozazolium, isoprothiolane, pefurazofamil, pyrimethanil, tebuconazole, tebuc, Famoxadone, pyrisoxazole, hymexazol, oxadixyl, ethaboxam, hymexazol, octhiolone, thiobensulam, dodecacylmorpholine, fenpropimorph, tridemorph, fenpiclonil, fludioxonil, fluazinam, pyrifenox, cyprodinil, boscalid, fluopicolide, pyrimethanil, cyprodinil, fluopyram, mepanipyrim, pyrimethanil, fenarimol, fenamiphos, dithianon, ethoxyquin, hydroxyquinoline, propoxymine, phenoxyquinoline, diethofencarb, iprovalicarb, benthiavalicarb, propamocarb, edifenphos, iprobenfos, pirifolin, tolclofos-methyl, blastin, kasugamycin, polyoxin, validamycin, jinggangmycin, streptomycin, metalaxyl, furalaxyl, benalaxyl, furalaxyl, furalazide, benomyl, trifloxystrobin, carbendazim, thiophanaton, thiophanate, triazolone, bupirimate, dimetridol, ethirimol, captafol, captan, folpet, vinclozolin, fluocinolone, dimethachlon, isoprothiolane, pyrifenozin, metconazole, quintozene, mancozeb, propineb, fosetyl-aluminum, sulfur, boldo, copper sulfate, cupric chloride, cuprous oxide, copper hydroxide, metrafenone, pencycuron, pyridazone, tetrachlorophthalide, pyroquilon, spiroxamine, tricyclazole, azinam-ethyl, dodine, iminoctadine, clonidine, niclosamide, bensulam, tolbutamide, indole ester, diuron, quinconone, probenazole, bronopol, iodomethane, metam, dichlofenamate, dazomet, isopropin, fosthiazate, thiotep, fenthion, ethoprophos, fenamiphos, dichlorvophos, chloprophos, clofos, thion, thiocarb, thion, dichlorvos, dichlor, Carbofuran, sulfuryl fluoride, dichloropropene, dichloroisonicotinic acid, probenazole; the total mass percentage content of the piperidine thiazole derivative in the obtained compound bactericide is 1-90 percent, and the mass percentage of the piperidine thiazole derivative and the commercial bactericide is 1 percent to 99 percent to 1 percent; the formulation suitable for the compound bactericide is selected from any one of the following formulations: wettable powders, microcapsule suspensions, dispersible liquid formulations, dispersible solid formulations, seed treatment emulsions, aqueous emulsions, macrogranules, microemulsions, oil suspensions, pesticide-coated seeds, water-soluble granules, soluble concentrates, water-dispersible granules, cuds, aerosols, chunk baits, sustained release chunks, concentrated baits, capsule granules, dry mix powders, emulsifiable concentrates, electrostatic sprays, water-in-oil emulsions, oil-in-water emulsions, aerosol canisters, fine granules, aerosol candles, aerosol canisters, aerosol sticks, seed treatment suspensions, aerosol tablets, aerosol pellets, granular baits, propellants, drift powders, ointments, hot fogging formulations, solid/liquid mixtures, liquid/liquid mixtures, cold fogging formulations, solid/solid mixtures, lacquers, seed treatment liquids, microgranules, oil-dispersible powders, tablet baits, concentrated jellies, pour-on formulations, Smearing agent, suspending emulsion, film-forming oil agent, soluble powder, seed treatment water soluble powder, ultra-low volume suspending agent, tracing powder, ultra-low volume liquid, steam releasing agent, and wet-mixed seed water dispersible powder; the plant suitable for the compound bactericide is selected from rice, wheat, barley, oat, corn, sorghum, sweet potato, cassava, soybean, sweet broad bean, pea, mung bean, small bean, cotton, silkworm, peanut, rape, sesame, sunflower, beet, sugarcane, coffee, cocoa, ginseng, fritillaria, rubber, coconut, oil palm, sisal, tobacco, tomato, pepper, radish, cucumber, Chinese cabbage, celery, tuber mustard, beet, rape, shallot, garlic, watermelon, melon, cantaloupe, papaya, apple, orange, peach, tea, potherb, bamboo shoot, hop, pepper, banana, papaya, orchid, bonsai; the compound bactericide is suitable for preventing and treating diseases and is selected from the following groups: wheat rust, wheat scab, wheat powdery mildew, wheat virus disease, wheat snow mold leaf blight, wheat helminthosporium leaf spot, wheat smut, wheat take-all, wheat sharp eyespot, wheat downy mildew, potato late blight, potato cancer, potato scab, potato early blight, potato ring rot, potato bacterial wilt, potato black shank, potato virus and viroid diseases, potato soft rot, potato dry rot, potato verticillium wilt, potato black nevus, potato bacterial wilt, potato ring rot, potato black shank, potato soft rot, cotton wilt, cotton leaf spot, russet leaf spot, cotton damping-off, cotton anthracnose, cotton wilt, cotton fusarium wilt, cotton wilt, rice sheath blight, rice leaf blight, flax leaf spot, wheat blight, wheat scab, wheat leaf spot, wheat scab, potato ring rot, potato leaf spot, potato black rot, potato leaf blight, rice blast, rice leaf blight, wheat scab, wheat rot, wheat scab, wheat scab, Sclerotinia rot of rice, bakanae disease of rice, downy mildew of rice, false smut of rice, sheath rot of rice, bacterial leaf blight of rice, bacterial leaf streak of rice, bacterial basal rot of rice, stripe disease of rice, dwarf of black streaked rice, black sclerotinia stem rot of rice, big spot of corn, small spot of corn, round spot of corn, brown spot of corn, sheath blight of corn, rust disease of corn, head smut of corn, bacterial wilt of corn, black powdery mildew of corn, dry rot disease of corn, virosis of corn and stem rot of corn, sclerotinia rot of colza, virosis of colza, downy mildew of colza, white rust disease of colza, root rot of soybean, sclerotinia rot of soybean, gray spot of soybean, virosis of soybean mosaic, nematode of soybean cyst, nematode of soybean root knot, rust disease of soybean, anthracnose of soybean, bacterial leaf blight of soybean, downy mildew of peanut, peanut bacterial leaf, bacterial leaf rot of soybean, bacterial wilt of peanut, bacterial leaf rot of soybean, bacterial leaf of soybean, Peanut stem rot, peanut root rot, peanut brown spot, peanut net blotch, peanut yellowing disease, peanut scab, tobacco bacterial wilt, tobacco wildfire, tobacco hollow stem disease, tobacco angular leaf spot, tobacco black shank, tobacco brown spot, tobacco frog eye disease, tobacco anthracnose, tobacco root black rot, tobacco fusarium root rot, tobacco damping off, tobacco leaf spot, tobacco powdery mildew, tobacco southern blight, tobacco black spot, tobacco mosaic disease, cucumber mosaic disease, tobacco leaf erosion, Chinese cabbage downy mildew, Chinese cabbage soft rot, Chinese cabbage dry burn heart disease, Chinese cabbage virus disease, Chinese cabbage black rot, Chinese cabbage anthracnose, Chinese cabbage clubrood, tomato bacterial spot, tomato late blight, tomato stalk rot, tomato powdery mildew, tomato damping off, tomato sunset leaf disease, tomato bacterial leaf blight, tomato yellow leaf curl leaf virus, tomato leaf curl leaf spot disease, tobacco leaf, Tomato leaf mold, tomato virus disease, tomato late blight, tomato damping-off and damping-off, tomato deformed fruit, tomato perforated fruit, tomato black ring virus disease, tomato rot stem nematode disease, tomato fruit bull disease, tomato black point root rot, tomato cladosporium cucumerinum, tomato heart rot, tomato root mold fruit rot, tomato low temperature disorder, tomato giant bud disease, tomato physiological leaf rolling disease, tomato damping-off, tomato flower and fruit drop, tomato bud blight, tomato soft rot, tomato stem rot, tomato damping-off, tomato sunscald, tomato scab, tomato red powdery mildew, tomato virus disease, tomato fruit cracking disease, tomato canker, tomato navel rot, tomato sesame leaf spot, tomato bacterial spot, tomato leaf spot virus disease, tomato yellow leaf curl virus disease, eggplant soft rot, eggplant sclerotinia rot, eggplant green rot, tomato bacterial blight, tomato bacterial wilt, tomato rot and bacterial wilt, tomato rot resistance, tomato bacterial, Eggplant brown streak disease, eggplant verticillium wilt, eggplant leaf spot disease, eggplant early blight, eggplant virus disease, eggplant leaf spot disease, eggplant leaf mold disease, eggplant powdery mildew, eggplant spot disease, eggplant coal spot disease, eggplant brown spot disease, eggplant black blight, eggplant anthracnose, eggplant root mold soft rot, eggplant blight, eggplant gray mold, eggplant stem basal rot, pepper green pepper virus disease, pepper early blight, pepper white spot disease, pepper leaf spot disease, pepper tiger skin disease, pepper soil mildew, pepper blight, pepper sclerotinia rot, pepper sunscald disease, pepper virus disease, pepper malformation, pepper navel rot, pepper soft rot, pepper scab, pepper stripe virus disease, pepper soft rot, pepper black mold, pepper spot blight, pepper black spot disease, pepper yellow wilt, pepper bacterial leaf spot disease, pepper brown rot, pepper bacterial leaf spot disease, pepper brown rot, Pepper root rot, pepper damping off, pepper anthracnose, pepper brown spot, pepper downy mildew, pepper gray mold, pepper leaf blight, pepper leaf mold, pepper damping-off, pepper blight, grape downy mildew, grape powdery mildew, grape brown spot, grape leaf roll, grape fanleaf disease, grape rust, grape ring spot, grape leaf spot, grape brown spot, grape ring spot, grape gray spot, grape young tip atrophy, grape mosaic, grape atrophy, grape stripe, grape golden yellow, grape infectious necrosis, grape yellow spot, grape ear bud disease, grape leaf vein necrosis, grape leaf spot virus, grape star, grape pierce disease, grape white rot, grape anthracnose, grape house blight, grape gray mold, grape black rot, grape house blight, grape coal spot disease, grape leaf blight, grape anthracnose, grape leaf spot disease, grape anthrac, Grape brown spot disease, grape mildew, grape bitter rot, grape branch rot, grape penicilliosis, grape alternaria rot, apple tree rot, apple dry rot, apple ring rot, apple branch canker, apple blister canker, apple red skin disease, apple stem blight, apple branch blight, apple anthracnose, apple core mildew, apple rust, apple blossom rot, apple brown rot, apple black rot, apple blight, apple smut, apple brown spot, apple alternaria leaf spot, apple gray spot, apple powdery mildew, apple scab, apple silver leaf disease, apple invasive root rot, apple southern blight, apple leaf rot, apple leaf violet rot, apple leaf rot, apple canker, apple rot, apple rust, apple leaf rust, apple mosaic, apple green wrinkle, apple leaf rot, apple leaf blight, apple leaf rot, apple leaf blight, apple leaf rot, apple leaf rot, Apple fruit rot, apple lobular disease, apple yellow leaf disease, apple bitter pox disease, apple water core disease, apple tiger's skin disease, red jade apple spot disease, golden crown apple rust, apple penicilliosis, apple soft rot, apple pulp pink rot, apple pulp brown stain, apple brown core disease, pear scab, pear ring rot, pear southern blight, pear tree rot, pear dry blight, pear rust, pear black spot, pear gray spot, pear brown spot, pear rust, pear top rot, pear fruit rot, pear yellow leaf disease, peach anthracnose, peach fruit rot, peach soft rot, peach ulcer, peach tree rot, peach brown rot, peach scab, peach teratopathy, peach smut, peach leaf rot, peach tree leaf curl, peach fungal leaf spot, peach tree bacterial leaf spot, peach tree perforation disease, peach leaf spot, peach leaf rust, peach leaf spot, peach leaf rot, peach leaf spot, peach, Peach gummosis, peach tree rot, peach tree stem blight, peach root canceration, peach root rot, peach root knot nematode disease, citrus yellow shoot disease, citrus dehiscence, citrus leaf shattering disease, citrus recession disease, citrus atrophy disease, citrus canker, citrus scab, citrus anthracnose, citrus foot rot, citrus resinoid disease, citrus gummosis, citrus soot leaf disease, citrus powdery mildew, citrus lipid point yellow spot disease, citrus lipoid point yellow spot disease, citrus red skin disease, citrus plaster disease, citrus seedling stage blight, citrus seedling blight, banana bunchy top disease, banana mosaic heart rot, banana fusarium wilt, banana cercospora leaf spot disease, banana endodiplospora leaf spot disease, banana sinomontana leaf spot disease, banana scab, banana leaf blast, banana leaf rot, banana crown rot, cabbage bacterial black spot disease, cabbage bacterial blight, black rot disease, banana, Cabbage black spot, cabbage brown spot, cabbage head break, cabbage virus disease, cabbage soft rot, cabbage early bolting disease, cabbage downy mildew, cabbage anthracnose, cabbage black shank, sugarcane pineapple disease, sugarcane smut, sugarcane ratoon stunting disease, sugarcane brown streak disease, sugarcane rust disease, sorghum smut, sorghum leaf spot, sorghum anthracnose, sorghum leaf spot, and sorghum leaf spot.

Example 10: the piperidine thiazole derivative provided by the invention, an agriculturally acceptable auxiliary agent, a commodity antiviral agent and a plant activator are combined to prepare a compound plant virus resisting agent and a plant activator, and the application comprises the following steps:

the piperidine thiazole derivative disclosed by the invention is combined with an agriculturally acceptable auxiliary agent, one or more commodity antiviral agents and a plant activator to prepare a compound plant virus resisting agent and a plant activator. The commercial antiviral agents, plant activators are selected from: benzothiadiazole, tiadinil, methidazole, 4-methyl-1, 2, 3-thiadiazole-5-carboxylic acid, 4-methyl-1, 2, 3-thiadiazole-5-sodium formate, 4-methyl-1, 2, 3-thiadiazole-5-ethyl formate, 4-bromomethyl-1, 2, 3-thiadiazole-5-ethyl formate, 4-iodomethyl-1, 2, 3-thiadiazole-5-ethyl formate, 4-bromomethyl-5-methyl-1, 2, 3-thiadiazole, 4-iodomethyl-5-methyl-1, 2, 3-thiadiazole, 4-dibromomethyl-1, 2, 3-thiadiazole-5-ethyl formate, methyl-5-ethyl formate, ethyl-methyl-4, 4-dibromomethyl-1, 3-thiadiazole-5-ethyl formate, and their pharmaceutically acceptable salts, 3, 4-dichloroisothiazole-5-carboxylic acid, 3, 4-dichloroisothiazole-5-sodium formate, ethyl 3, 4-dichloroisothiazole-5-carboxylate, DL-beta-aminobutyric acid, ribavirin, antofine, ningnanmycin, methicillin, salicylic acid, pyriminomycin, dichloroisonicotinic acid, probenazole, validamycin; the total mass percentage content of the piperidine thiazole derivative in the obtained compound plant virus resisting agent and plant activator is 1-90%, and the mass percentage of the piperidine thiazole derivative, the commercial antiviral agent and the plant activator is 1: 99-99: 1; the dosage forms of the compound plant virus resisting agent and the plant activator are selected from wettable powder, microcapsule suspending agent, dispersible liquid preparation, dispersible solid preparation, seed treatment emulsion, aqueous emulsion, large granule, microemulsion, oil suspending agent, seed coated with pesticide, water soluble granule, soluble concentrate, water dispersible granule, poison valley, aerosol, massive poison bait, slow release block, poison bait, capsule granule, dry mixed seed powder, missible oil, electrostatic spray, water-in-oil emulsion, oil-in-water emulsion, smoke tank, fine granule, smoke candle, smoke cylinder, smoke rod, seed treatment suspending agent, smoke tablet, smoke pill, granular poison bait, gas generating agent, drift powder, ointment, hot fogging concentrate, solid/liquid mixed packaging agent, liquid/liquid mixed packaging agent, cold fogging concentrate, solid/solid mixed packaging agent, medicinal paint, seed treatment suspending agent, micro-particle agent, Any one of oil dispersible powder, sheet poison bait, concentrated colloid, sprinkling agent, smearing agent, suspending emulsion, film forming oil agent, soluble powder, seed treatment water soluble powder, ultra-low volume suspending agent, tracing powder, ultra-low volume liquid, steam releasing agent, and wet-mixed seed water dispersible powder; the plant suitable for the compound plant virus resisting agent and the plant activating agent is selected from rice, wheat, barley, oat, corn, sorghum, sweet potato, cassava, soybean, lotus bean, broad bean, pea, mung bean, small bean, cotton, silkworm, peanut, rape, sesame, sunflower, beet, sugarcane, coffee, cocoa, ginseng, fritillaria, rubber, coconut, oil palm, sisal, tobacco, tomato, chili, radish, cucumber, Chinese cabbage, celery, tuber mustard, beet, rape, shallot, garlic, watermelon, melon, cantaloupe, papaya, apple, orange, peach tree, tea, wild cabbage, bamboo shoot, hop, pepper, banana, papaya, orchid and bonsai; the compound plant virus resisting agent and the plant activator are suitable for virus diseases selected from any one of rice dwarf disease, yellow dwarf disease, stripe disease, tomato fern leaf virus disease, pepper mosaic virus disease, tobacco vein necrosis virus disease, maize dwarf mosaic disease, cauliflower mosaic virus, citrus virus disease, cymbidium mosaic virus and cymbidium ringspot virus.

Example 11: the piperidine thiazole derivative, the agriculturally acceptable auxiliary agent and the commercial acaricide are combined to prepare a compound acaricide and the application thereof in preventing and controlling plant mites:

the piperidine thiazole derivative, the agriculturally acceptable auxiliary agent and one or more commercial acaricides are combined to prepare a compound acaricide and the application of the compound acaricide in preventing and controlling plant mites. The commercial acaricide is selected from azocyclotin, cyhexatin, fenbutatin oxide, triphosphatin, chlorfenvinphos, methylcarbamate, bafenphos, dichlorvos, heptenophos, metophos, monocrotophos, phosphorus dibromide, chlorpyrifos, pyrimidophos, chloromethion, omethoate, dichlorvos, ethion, malathion, chlorfenvinphos, fenthion, phoxim, pirimiphos, methamidophos, amiphos, phos, flupropathrin, bifenthrin, cyhalothrin, lambda-cyhalothrin, fenpropathrin, flucythrinate, flumethrin, fluvalinate, brofluvalinate, bifenthrin, fenobuconazole, fenobucarb, carbofuran, aldicarb, methiocarb, dichlorvone, carbofuran, monocarb, benomyl, clofenpropathrin, carbofuran, carbosulfan, thion, thio, Varroamidine, amitraz, chlordimeform, benzamate, fenisobromolate, cyflumetofen, fenaminoquinone, fluaphis, flufenoxuron, dactinomycin, chlortetracycline, thuringiensis, miticide, liuyangmycin, abamectin, doramectin, eprinomectin, ivermectin, selamectin, moxidectin, pyrethrin, nicotine, matrine, azadirachtin, rotenone, tebufenpyrad, pyridaben, fenpyroximate, clofentezine, propargite, hexythiazox, fluacrypyrim, pyrimidifen, miticide, propargite, pyridaben; the total mass percentage of the piperidine thiazole derivative in the composition of the compound acaricide is 1-90%, and the mass percentage of the piperidine thiazole derivative and the commercial acaricide is 1: 99-99: 1; the dosage form of the compound acaricide is selected from wettable powder, microcapsule suspending agent, dispersible liquid preparation, dispersible solid preparation, seed treatment emulsion, aqueous emulsion, large granule preparation, microemulsion, oil suspending agent, seed coated with pesticide, water soluble granule preparation, soluble concentrate preparation, water dispersible granule preparation, poison valley, aerosol, block poison bait, sustained release block, concentrated poison bait, capsule granule preparation, dry mixed seed powder, missible oil, electrostatic spray, water-in-oil emulsion, oil-in-water emulsion, smoke tank, fine granule preparation, smoke candle, smoke cylinder, smoke rod, seed treatment suspending agent, smoke tablet, smoke pill, granular poison bait, gas former, drift powder, ointment, hot fogging concentrate, solid/liquid mixed agent, liquid/liquid mixed agent, cold liquid, solid/solid mixed agent, medicinal paint, seed treatment atomizing agent, oil dispersible powder, oil, solid/liquid mixed agent, solid/solid mixed agent, medicinal paint, seed treatment atomizing agent, oil dispersible powder, any one of a flaky poison bait, a concentrated colloid agent, a pouring agent, a smearing agent, a suspending emulsion, a film-forming oil agent, a soluble powder, a seed treatment water-soluble powder, an ultra-low volume suspending agent, a tracing powder, an ultra-low volume liquid, a steam releasing agent and a wet-mixed seed water-dispersible powder; the plant suitable for the compound acaricide is selected from rice, wheat, barley, oat, corn, sorghum, sweet potato, cassava, soybean, sweet broad bean, pea, mung bean, small bean, cotton, silkworm, peanut, rape, sesame, sunflower, beet, sugarcane, coffee, cocoa, ginseng, fritillaria, rubber, coconut, oil palm, sisal, tobacco, tomato, pepper, radish, cucumber, Chinese cabbage, celery, tuber mustard, beet, rape, shallot, garlic, watermelon, melon, cantaloupe, papaya, apple, orange, peach, tea, potherb, bamboo shoot, hop, pepper, banana, papaya, orchid, bonsai; the acarid suitable for the compound acaricide is selected from harmful acarids of Tetranychidae, Paralichthys, Furoids, gall acaridae, Tetranychus, gall acaridae, which are agricultural harmful acarids in the world, forestry harmful acarids, horticultural harmful acarids and sanitary harmful acarids.

Table 2 in vitro bacteriostatic activity of isothiazolidinothiazole derivative V of the present invention and its intermediate (inhibition rate of 50 μ g/ml/%)

PI: the late blight of potato, its latin name is: phytophthora infestans (Mont.) de barr, CA: peanut brown spot pathogen, its latin name is: cercospora arachidicola, AS: tomato early blight, its latin name is: alternaria solani, BC: the cucumber botrytis cinerea with the latin name as follows: botrytis cinerea, GZ: wheat scab, its latin name is: gibberella zeae, PP: apple ring rot, its latin name is: physiosporia piricola, SS: sclerotinia sclerotiorum, its latin name is: sclerotina sclerotiorum, RC: rhizoctonia cerealis, with the latin name: rhizoctonia cerealis, PS: rhizoctonia solani, the Latin name of which is: pellicularia sasakii.

TABLE 3 precise virulence determination results (EC) for isothiazolothiazole derivative V and its intermediates of the present invention₅₀Microgram/ml)

Table 4 chemical structures of other highly active thiazoleperidine compounds discovered by the inventors' problem group

TABLE 5 Precisive virulence of other highly active thiazoleperidine compounds discovered by the inventors' problem group

Compound (I)	Fungi	Linear regression equation	R2	EC50(μg/mL)
					IIA-13	Rhizoctonia cerealis (Fr.) Kuntze	y＝0.6141x+4.0178	0.9600	39.76
IIA-17	Sclerotinia sclerotiorum	y＝0.5801x+4.1331	0.9830	31.22
					IIA-19	Sclerotinia sclerotiorum	y＝0.8251x+3.7745	0.9350	30.58
IIA-23	Sclerotinia sclerotiorum	y＝0.8898x+4.3288	0.9195	5.68
					IIA-27	Sclerotinia sclerotiorum	y＝0.4923x+4.6263	0.9350	5.74
Azoxystrobin	Sclerotinia sclerotiorum	y＝0.6749x+4.4378	0.8700	6.81
					IIB-13	Cucumber gray mold	y＝0.9484x+3.5389	0.9470	34.72
Azoxystrobin	Cucumber gray mold	y＝1.0431x+3.5389	4.0344	8.43

Claims (4)

1. An isothiazole bithiazole derivative is characterized in that: has a general structural formula shown as formula V:

according to different substituents R, the specific compound name is as follows:

3, 4-dichloro-5- (2- (piperidin-4-yl) thiazol-4-yl) isothiazole

3, 4-dichloro-5- (2- (piperidin-4-yl) thiazol-4-yl) isothiazole hydrochloride

4- (4- (3, 4-Dichloroisothiazol-5-yl) thiazol-2-yl) piperidine-1-carboxylic acid tert-butyl ester

(4- (4- (3, 4-dichloroisothiazol-5-yl) thiazol-2-yl) piperidin-1-yl) (phenyl) methanone

Cyclohexyl (4- (4- (3, 4-dichloroisothiazol-5-yl) thiazol-2-yl) piperidin-1-yl) methanone

Cyclopropyl (4- (4- (3, 4-dichloroisothiazol-5-yl) thiazol-2-yl) piperidin-1-yl) methanone

1- (4- (4- (3, 4-dichloroisothiazol-5-yl) thiazol-2-yl) piperidin-1-yl) -2-phenyleth-1-one

1- (4- (4- (3, 4-dichloroisothiazol-5-yl) thiazol-2-yl) piperidin-1-yl) -2- (3-fluorophenyl) ethan-1-one

2-cyclopropyl-1- (4- (4- (3, 4-dichloroisothiazol-5-yl) thiazol-2-yl) piperidin-1-yl) ethan-1-one

(4- (4- (3, 4-dichloroisothiazol-5-yl) thiazol-2-yl) piperidin-1-yl) (4-fluorophenyl) methanone

(4- (4- (3, 4-dichloroisothiazol-5-yl) thiazol-2-yl) piperidin-1-yl) (3-fluorophenyl) methanone

(4- (4- (3, 4-dichloroisothiazol-5-yl) thiazol-2-yl) piperidin-1-yl) (2-fluorophenyl) methanone

(4- (4- (3, 4-dichloroisothiazol-5-yl) thiazol-2-yl) piperidin-1-yl) (2, 6-difluorophenyl) methanone

(4-chlorophenyl) (4- (4- (3, 4-dichloroisothiazol-5-yl) thiazol-2-yl) piperidin-1-yl) methanone

(4- (4- (3, 4-dichloroisothiazol-5-yl) thiazol-2-yl) piperidin-1-yl) (2, 4-dichlorophenyl) methanone

(3-chlorophenyl) (4- (4- (3, 4-dichloroisothiazol-5-yl) thiazol-2-yl) piperidin-1-yl) methanone

(4-bromophenyl) (4- (4- (3, 4-dichloroisothiazol-5-yl) thiazol-2-yl) piperidin-1-yl) methanone

(3-bromophenyl) (4- (4- (3, 4-dichloroisothiazol-5-yl) thiazol-2-yl) piperidin-1-yl) methanone

(4- (4- (3, 4-dichloroisothiazol-5-yl) thiazol-2-yl) piperidin-1-yl) (3- (trifluoromethyl) phenyl) methanone

(4- (4- (3, 4-dichloroisothiazol-5-yl) thiazol-2-yl) piperidin-1-yl) (4-methoxyphenyl) methanone

(4- (4- (3, 4-dichloroisothiazol-5-yl) thiazol-2-yl) piperidin-1-yl) (p-tolyl) methanone

4- (4- (4- (3, 4-dichloroisothiazol-5-yl) thiazol-2-yl) piperidine-1-carbonyl) benzonitrile

(4- (4- (3, 4-dichloroisothiazol-5-yl) thiazol-2-yl) piperidin-1-yl) (1-phenyl-5- (trifluoromethyl) -1H-pyrazol-4-yl) methanone

(4- (4- (3, 4-dichloroisothiazol-5-yl) thiazol-2-yl) piperidin-1-yl) (1- (4-fluorophenyl) -5- (trifluoromethyl) -1H-pyrazol-4-yl) methanone

(1- (4-chlorophenyl) -5- (trifluoromethyl) -1H-pyrazol-4-yl) (4- (4- (3, 4-dichloroisothiazol-5-yl) thiazol-2-yl) piperidin-1-yl) methanone

(1- (4-bromophenyl) -5- (trifluoromethyl) -1H-pyrazol-4-yl) (4- (4- (3, 4-dichloroisothiazol-5-yl) thiazol-2-yl) piperidin-1-yl) methanone

(4- (4- (3, 4-dichloroisothiazol-5-yl) thiazol-2-yl) piperidin-1-yl) (5- (trifluoromethyl) -1- (4- (trifluoromethyl) phenyl) -1H-pyrazol-4-yl) methanone

(4- (4- (3, 4-dichloroisothiazol-5-yl) thiazol-2-yl) piperidin-1-yl) (1- (2, 4-dichlorophenyl) -5- (trifluoromethyl) -1H-pyrazolopiperidin-4-yl) methanone

(4- (4- (3, 4-dichloroisothiazol-5-yl) thiazol-2-yl) piperidin-1-yl) (1- (3-fluorophenyl) -5- (trifluoromethyl) -1H-pyrazol-4-yl) methanone

(5-chloro-1-phenyl-3- (trifluoromethyl) -1H-pyrazol-4-yl) (4- (4- (3, 4-dichloroisothiazol-5-yl) thiazol-2-yl) piperidin-1-yl) methanone

(5-chloro-1- (4-fluorophenyl) -3- (trifluoromethyl) -1H-pyrazol-4-yl) (4- (4- (3, 4-dichloroisothiazol-5-yl) thiazol-2-yl) piperidin-1-yl) methanone

(5-chloro-1- (4-chlorophenyl) -3- (trifluoromethyl) -1H-pyrazol-4-yl) (4- (4- (3, 4-dichloroisothiazol-5-yl) thiazol-2-yl) piperidin-1-yl) methanone

(1- (4-bromophenyl) -5-chloro-3- (trifluoromethyl) -1H-pyrazol-4-yl) (4- (4- (3, 4-dichloroisothiazol-5-yl) thiazol-2-yl) piperidin-1-yl) methanone

(5-chloro-3- (trifluoromethyl) -1- (4- (trifluoromethyl) phenyl) -1H-pyrazol-4-yl) (4- (4- (3, 4-dichloroisothiazol-5-yl) thiazol-2-yl) piperidin-1-yl) methanone

(4- (4- (3, 4-dichloroisothiazol-5-yl) thiazol-2-yl) piperidin-1-yl) (5- (difluoromethyl) -1-phenyl-1H-pyrazol-4-yl) methanone

(4- (4- (3, 4-dichloroisothiazol-5-yl) thiazol-2-yl) piperidin-1-yl) (5- (difluoromethyl) -1- (4-fluorophenyl) -1H-pyrazol-4-yl) methanone

(1- (4-chlorophenyl) -5- (difluoromethyl) -1H-pyrazol-4-yl) (4- (4- (3, 4-dichloroisothiazol-5-yl) thiazol-2-yl) piperidin-1-yl) methanone

(1- (4-bromophenyl) -5- (difluoromethyl) -1H-pyrazol-4-yl) (4- (4- (3, 4-dichloroisothiazol-5-yl) thiazol-2-yl) piperidin-1-yl) methanone

(4- (4- (3, 4-dichloroisothiazol-5-yl) thiazol-2-yl) piperidin-1-yl) (1- (2, 4-dichlorophenyl) -5- (difluoromethyl) -1H-pyrazolopiperidin-4-yl) methanone

(4- (4- (3, 4-dichloroisothiazol-5-yl) thiazol-2-yl) piperidin-1-yl) (3- (difluoromethyl) -1-methyl-1H-pyrazol-4-yl) methanone

(4- (4- (3, 4-dichloroisothiazol-5-yl) thiazol-2-yl) piperidin-1-yl) (1-methyl-1H-pyrazol-4-yl) methanone

1- (4- (4- (3, 4-dichloroisothiazol-5-yl) thiazol-2-yl) piperidin-1-yl) -2- (3, 5-dimethyl-1H-pyrazol-1-yl) ethan-1-one

1- (4- (4- (3, 4-dichloroisothiazol-5-yl) thiazol-2-yl) piperidin-1-yl) -2- (5-methyl-3- (trifluoromethyl) -1H-pyrazol-1-yl) ethan-1-one

(3-bromo-1- (3-chloropyridin-2-yl) -1H-pyrazol-5-yl) (4- (4- (3, 4-dichloroisothiazol-5-yl) thiazol-2-yl) piperidin-1-yl) piperi dine-1-yl) methanone

3- (4- (3, 4-Dichloroisothiazol-5-yl) thiazol-2-yl) piperidine-1-carboxylic acid tert-butyl ester

3, 4-dichloro-5- (2- (piperidin-3-yl) thiazol-4-yl) isothiazole

1- (3- (4- (3, 4-dichloroisothiazol-5-yl) thiazol-2-yl) piperidin-1-yl) ethan-1-one

1- (3- (4- (3, 4-dichloroisothiazol-5-yl) thiazol-2-yl) piperidin-1-yl) prop-2-en-1-one

(3- (4- (3, 4-dichloroisothiazol-5-yl) thiazol-2-yl) piperidin-1-yl) (phenyl) methanone

(3- (4- (3, 4-dichloroisothiazol-5-yl) thiazol-2-yl) piperidin-1-yl) (3-fluorophenyl) methanone

(3- (4- (3, 4-dichloroisothiazol-5-yl) thiazol-2-yl) piperidin-1-yl) (3- (trifluoromethyl) phenyl) methanone

(3- (4- (3, 4-dichloroisothiazol-5-yl) thiazol-2-yl) piperidin-1-yl) (3-methoxyphenyl) methanone

(3- (4- (3, 4-dichloroisothiazol-5-yl) thiazol-2-yl) piperidin-1-yl) (3-nitrophenyl) methanone

(3-chlorophenyl) (3- (4- (3, 4-dichloroisothiazol-5-yl) thiazol-2-yl) piperidin-1-yl) methanone

(3- (4- (3, 4-dichloroisothiazol-5-yl) thiazol-2-yl) piperidin-1-yl) (m-tolyl) methanone

(3-bromophenyl) (3- (4- (3, 4-dichloroisothiazol-5-yl) thiazol-2-yl) piperidin-1-yl) methanone.

2. A pesticidal composition comprising the isothiazolium bithiazole derivative V described in claim 1 as an active ingredient in an amount of 0.1 to 99% by mass, 99.9 to 1% by mass of a solid or liquid adjuvant, and optionally 0 to 25% by mass of a surfactant.

3. Use of the isothiazolidinothiazole derivative V of claim 1 for the preparation of fungicides.

4. Use of the isothiazolidinothiazole derivative V of claim 1 for the preparation of insecticides.