CN111675706A - Isothiazole bithiazole amide derivatives, and preparation method and application thereof - Google Patents
Isothiazole bithiazole amide derivatives, and preparation method and application thereof Download PDFInfo
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- C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
- C07D417/04—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings directly linked by a ring-member-to-ring-member bond
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- A01N43/00—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds
- A01N43/72—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with nitrogen atoms and oxygen or sulfur atoms as ring hetero atoms
- A01N43/80—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with nitrogen atoms and oxygen or sulfur atoms as ring hetero atoms five-membered rings with one nitrogen atom and either one oxygen atom or one sulfur atom in positions 1,2
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- A01N43/00—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds
- A01N43/72—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with nitrogen atoms and oxygen or sulfur atoms as ring hetero atoms
- A01N43/84—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with nitrogen atoms and oxygen or sulfur atoms as ring hetero atoms six-membered rings with one nitrogen atom and either one oxygen atom or one sulfur atom in positions 1,4
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Abstract
The invention provides isothiazole bithiazole amide derivatives, a preparation method and application thereof, and relates to 3, 4-dichloroisothiazole bithiazole amide derivatives, wherein the chemical structure general formula of the isothiazole bithiazole amide derivatives is shown in a formula IV:
Description
Technical Field
The technical scheme of the invention relates to isothiazole amide compounds, in particular to isothiazole bithiazole amide derivatives.
Background
Heterocyclic compounds are widely distributed in nature and play a crucial role in the metabolism of all living cells. According to the current pesticide development situation, nitrogen-containing heterocyclic compounds are still the key point of chemical pesticide research, wherein thiazole and isothiazole hybridization plays a crucial role in medicinal chemistry due to a unique conjugated system.
Thiazole and isothiazole belong to nitrogen-containing, sulfur-containing and aromatic heterocyclic compounds; substituted thiazoles have some of the following characteristics: relatively high stability, easy synthesis, lactone bactericidal unit, high hydrophilicity and lipophilicity, and easy metabolism. (Chawla A, et al. journal of Global Trends in Pharmaceutical Sciences, 2014, 5 (2): 1641-1648.). They are widely used in the fields of medicines and agricultural chemicals, such as the commercial bactericides isotianil (isotianil), oryzaline (amicarthiazol), thifluzamide (thifluzamide), ethaboxam (ethaboxam), benthiavalicarb (benthiavalicarb), and oxathiapiprolin (oxathiapigenin), and the like.
The pest control is an indispensable link in the agricultural production process, chemical control is the most commonly used and most effective control method at present, but due to abuse of drugs, serious resistance problems occur, so that the research of designing novel pesticide varieties with high efficiency, low toxicity and broad spectrum and biological activity is always focused.
According to the characteristics of pesticide creation, an active substructure splicing principle is utilized, an isothiazole group with induced disease-resistant activity is introduced into a thiazole amide structure with biological activity, and a class of isothiazole bithiazole amide derivatives, a preparation method and application thereof are designed and synthesized, and systematic screening and evaluation of biological activity are simultaneously carried out, so that more green pesticide candidate varieties with high activity, low resistance risk and high environmental compatibility are discovered.
Disclosure of Invention
The technical problem to be solved by the invention is as follows: provides a class of isothiazole bithiazole amide derivatives, provides biological activity of the compounds for regulating and controlling agricultural, horticultural and sanitary and forestry plant pathogens and a determination method thereof, and simultaneously provides applications 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 general chemical structure formula of the isothiazole bithiazole amide derivatives with bactericidal activity in the agricultural field, the horticultural field and the forestry field is shown as formula IV:
wherein n is 0, 1, 2, 3, 4; r is selected from: hydrogen, C1-C6Alkyl radical, C1-C6Haloalkyl, C1-C6Alkoxy radical, C1-C6Haloalkoxy, C2-C6Alkenyl radical, C2-C6Haloalkenyl, C2-C6Alkynyl, C2-C6Halogenated alkynyl, hydroxy, C3-C6Cycloalkyl, substituted piperidin-1-yl, substituted morpholin-1-yl, substituted tetrahydropyrroln-1-yl, phenyl, or halogen substitutionOr C is phenyl1-C6Alkyl-substituted phenyl or C1-C6Haloalkyl-substituted phenyl or C3-C6Cycloalkyl-substituted phenyl, or nitro-substituted phenyl, or C2-C6Phenyl substituted by alkenyl, or C2-C6Phenyl substituted by haloalkenyl, or C3-C6Phenyl substituted by cycloalkenyl, or C2-C6Alkynyl-substituted phenyl or C2-C6Phenyl or C substituted by haloalkynyl3-C6Cycloalkynyl-substituted phenyl, pyridyl, or halogen-substituted pyridyl, or C1-C6Alkyl-substituted pyridyl, or C1-C6Haloalkyl-substituted pyridyl, or C3-C6Cycloalkyl-substituted pyridyl or nitro-substituted pyridyl, or C2-C6Alkenyl-substituted pyridyl, or C2-C6Haloalkenyl-substituted pyridyl, or C3-C6Cycloalkenyl-substituted pyridyl, or C2-C6Alkynyl-substituted pyridyl or C2-C6Halogenoalkynyl-substituted pyridyl or C3-C6Cycloalkynyl-substituted pyridyl, pyrimidinyl, or halo-substituted pyrimidinyl, or C1-C6Alkyl-substituted pyrimidinyl, or C1-C6Pyrimidinyl substituted by haloalkyl, or C3-C6Cycloalkyl-substituted pyrimidinyl, or nitro-substituted pyrimidinyl, or C2-C6Alkenyl-substituted pyrimidinyl, or C2-C6Pyrimidinyl substituted by haloalkenyl, or C3-C6Pyrimidinyl substituted by cycloalkenyl, or C2-C6Alkynyl-substituted pyrimidinyl or C2-C6Halogenoalkynyl-substituted pyrimidinyl or C3-C6Cycloalkynyl-substituted pyrimidinyl, substituted five-or six-membered heteroaryl having 1 or 2N atoms, substituted five-or six-membered heteroaryl having 1 or 2S atoms, substituted five-or six-membered heteroaryl having 1 or 2O atoms, substituted five-or six-membered heteroaryl having 1N atom and 1S atom, substituted five-or six-membered heteroaryl having 1N atom and 1O atom, substituted one having 1N atom and 1O atomA substituted five-or six-membered heteroaryl group, 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.
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 amide derivative comprises the following steps:
wherein n is 0, 1, 2, 3, 4; r is selected from: 3-methylphenylethyl, 2-chlorophenylethyl, phenylbutyl, 3-bromophenylmethyl, 1-methylpiperidin-4-yl, (2-ethyl) morpholin-4-yl, 4-fluorophenylmethyl.
The specific method for synthesizing the isothiazole bithiazole amide derivative and measuring the biological activity comprises the following steps of: monitoring by thin layer chromatography, yield
A. Preparation of compound IV:
adding 3 mmol of compound II into a 100 ml round-bottom flask, adding solvent dichloromethane solution and 3.6 mmol of acid-binding agent triethylamine, finally adding 3.6 mmol of amino substituent, and stirring at room temperature for 3 hours; after the reaction is completely monitored by thin-layer chromatography, decompression concentration is carried out firstly, the solvent is removed, ethyl acetate is used for dilution, water washing is carried out, ethyl acetate is used for extraction for 3 times, organic layers are combined, saturated sodium chloride is used for washing the organic layers, anhydrous sodium sulfate is used for drying, suction filtration is carried out, the solvent is removed under reduced pressure, the residue is purified by 100-200-mesh silica gel column chromatography, the eluent is petroleum ether and ethyl acetate at the temperature of 60-90 ℃, the volume ratio is 20: 1-10: 1 according to the characteristics of products, and the solid compound IV is obtained, and the yield is 20-90%. Relevant parameters for compound IV are shown in table 1.
And (3) monitoring by thin-layer chromatography: production yield thin layer chromatography monitoring b. preparation of compound II:
a100-ml round-bottom flask was charged with 3 mmol of Compound I, dissolved in an ethanol solution, and 3.3 mmol of thioamino monoethyl ester was added thereto and heated under reflux for 3 hours. After the thin-layer chromatography monitoring reaction is completed, firstly carrying out reduced pressure concentration to remove the solvent, diluting with ethyl acetate, washing with saturated sodium bicarbonate, extracting with ethyl acetate for 3 times, combining organic layers, washing the organic layers with saturated sodium chloride, drying with anhydrous sodium sulfate, carrying out suction filtration, removing the solvent under reduced pressure, carrying out chromatography purification on the residue through a 100-200-mesh silica gel column, wherein an eluent is petroleum ether and ethyl acetate at the temperature of 60-90 ℃, and the volume ratio of the petroleum ether to the ethyl acetate is 20: 1, so as to obtain a solid compound II, and the yield is 36%. The amount of compound II prepared and the volume of the reaction vessel are scaled up or down accordingly.
C. The determination of the bactericidal activity of the isothiazole bithiazole amide derivative IV of the invention comprises the following steps:
the bactericidal or bacteriostatic activity of the isothiazole bithiazole amide derivative IV is measured by a thallus growth rate method, and the method comprises the following specific steps: dissolving 1.8 mg of sample in 2 drops of N, N-dimethylformamide, diluting with a water solution containing a certain amount of Tween 20 emulsifier to 500 micrograms/ml of medicament, sucking 1 ml of the medicament to be tested in a culture dish under an aseptic condition, adding 9 ml of PDA culture medium, shaking uniformly to prepare a medicament-containing flat plate with the concentration of 50 micrograms/ml, taking the flat plate added with 1 ml of sterile water as a blank control, cutting a bacterial disc by a puncher with the diameter of 4 mm along the outer edge of hypha, moving the bacterial disc to the medicament-containing flat plate, placing the bacterial disc in an equilateral triangle, repeating the treatment for 3 times, placing the culture dish in a constant temperature incubator with the temperature of 24 +/-1 ℃ for culture, investigating the expansion diameter of each treated bacterial disc after the diameter of the control bacterial colony is expanded to be more than 2 cm, calculating the relative bacteriostasis rate by comparing with the blank control, wherein the strain is the species of most typical plant pathogenic bacteria actually generated in the field in agricultural production of China, the code numbers and names are as follows: AS: tomato early blight, its latin name is: alternaria solani, BC: the cucumber botrytis cinerea with the latin name as follows: botrytis cinerea, 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. CA: peanut brown spot pathogen, its latin name is: cercospora arachidicola.
The invention has the beneficial effects that: the isothiazole bithiazole amide derivative IV is subjected to lead optimization, and the isothiazole bithiazole amide derivative IV is screened for antibacterial activity.
The synthesis, biological activity and application of isothiazole bithiazole amide derivative IV 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:
and (3) monitoring by thin-layer chromatography: 1, yield thin layer chromatography monitoring: yield example 1: preparation of Compound IV-1:
adding 3 mmol of compound II into a 100 ml round-bottom flask, adding 30 ml of dichloromethane solution and 3.6 mmol of acid-binding agent triethylamine, finally adding 3.6 mmol of p-fluorophenylethylamine, and stirring at room temperature for 3 hours; after the reaction is completely monitored by thin-layer chromatography, decompression concentration is carried out firstly, the solvent is removed, ethyl acetate is used for dilution, water washing is carried out, ethyl acetate is used for extraction for 3 times, organic layers are combined, saturated sodium chloride is used for washing the organic layers, anhydrous sodium sulfate is used for drying, suction filtration is carried out, the solvent is removed under reduced pressure, the residue is purified by 100-200-mesh silica gel column chromatography, the eluent is petroleum ether and ethyl acetate with the temperature of 60-90 ℃, the volume ratio of the petroleum ether to the ethyl acetate is 15: 1, the solid compound IV-B-1 is obtained, and the yield is 24. Of the compound1H NMR(400MHz，CDCl3)8.40(s，1H)，7.57(s，1H)，7.38(s，2H)，7.08(t，J＝8.0Hz，2H)，4.67(d，J＝5.5Hz，2H).
Example 2: the bactericidal activity determination result of the isothiazole bithiazole amide derivative IV of the invention is as follows:
the codes and names of the common plant pathogenic fungi tested by the invention are as follows: PI: the late blight of potato, its latin name is: phytophthora infestans (Mont.) de Bary, SS: sclerotinia sclerotiorum, its latin name is: sclerotina sclerotiorum, BC: the cucumber botrytis cinerea with the latin name as follows: botrytis cinerea, GZ: wheat scab, its latin name is: gibberella zeae, AS: tomato early blight, its latin name is: alternariolani, RC: rhizoctonia cerealis, with the latin name: rhizoctonia cerealis, PP: apple ring rot, its latin name is: physiosporia piricola, PS: rhizoctonia solani, the Latin name of which is: pellicularia sasakii. CA: peanut brown spot pathogen, its latin name is: cercospora arachidicola. These species represent the species of most pathogenic bacteria occurring in the field in agricultural production.
The results of the bacteria growth rate method are shown in table 2, and table 2 shows that most of the compounds of the invention have certain bacteriostatic activity on the tested bacteria under the in vitro condition at 50 micrograms/ml. The activity test result on potato late blight bacteria shows that the bacteriostatic activity of all the compounds is not high, but ZS-93 is higher than isotianil (the inhibition rate on potato late blight bacteria is 3%) and thifluzamide (the inhibition rate on potato late blight bacteria is 20%). The activity test on sclerotinia sclerotiorum shows that all the compounds have higher bacteriostatic activity, wherein ZS-93, ZS-94 and ZS-95 are higher than isotianil (the inhibition rate on sclerotinia sclerotiorum is 52%). The activity test on the botrytis cinerea shows that the activity of the compound is better, wherein the bacteriostatic activity of ZS-90, ZS-92 and ZS-93 is higher than that of isotianil (the inhibition rate on the botrytis cinerea is 43%). The activity test on the wheat scab bacteria shows that the bacteriostatic activity of the compounds ZS-94 and ZS-95 is higher than that of isotianil (the inhibition rate on cucumber botrytis cinerea is 10%) and thifluzamide (the inhibition rate on cucumber botrytis cinerea is 20%). The activity result on the early blight of tomato shows that the bacteriostatic activity of most compounds is higher than or equal to that of isotianil (the inhibition rate on the early blight of tomato is 11%), and the bacteriostatic activity of all compounds is lower than that of thifluzamide (the inhibition rate on the early blight of tomato is 69%). The activity test of the rhizoctonia cerealis shows that most compounds have lower bacteriostatic activity. The activity test on the physalospora piricola shows that the activity of most of compounds is higher than that of isotianil (the inhibition rate on the physalospora piricola is 20%). The activity test on rhizoctonia solani shows that all the compounds show certain bacteriostatic activity, and the ZS-93 activity is higher than that of isotianil (the inhibition rate on rhizoctonia solani is 11%) and thifluzamide (the inhibition rate on rhizoctonia solani is 17%). The activity test of the peanut brown spot germ shows that the bacteriostatic activity of all the compounds is lower than that of thifluzamide (the inhibition rate of the peanut brown spot germ is 90 percent).
Example 3: the application of the isothiazole bithiazole amide derivative IV in the preparation of the pesticide composition comprises the following steps:
the isothiazole bithiazole amide derivative IV can be compounded with other commercial insecticides, acaricides, bactericides, antiviral agents or plant activators to prepare a pesticide composition, the composition comprises the isothiazole bithiazole amide derivative IV and an intermediate thereof as active ingredients, the mass percentage of the active ingredients and other commercial insecticides, acaricides, bactericides, antiviral agents or plant activators is 1 percent to 99 percent to 1 percent, the content of the active ingredients is 0.1 to 99.9 percent by weight, 99.9 to 0.1 percent by weight of solid or liquid auxiliaries, and optionally 0 to 25 percent by weight of surfactants.
Example 4: the application of the isothiazole bithiazole amide derivative IV and the pesticide composition in preventing and treating the agricultural and forestry and horticultural plant insect pests:
all isothiazole bithiazole amide derivatives IV of the invention are combined with any one or two of commercial insecticides to form an insecticidal composition for preventing and treating agricultural and forestry and horticultural plant insect pests; the commodity pesticide is a pesticide which is allowed to be registered and used by the agricultural administration part of China; the mass percentage of the isothiazole bithiazole amide derivative IV and the intermediate thereof in the insecticidal composition is 1-90%, 99-10% of solid or liquid auxiliary agent and optionally 0-25% of surfactant, and the proportion of the isothiazole bithiazole amide derivative IV and the commercial insecticide is 1: 99-99: 1%; the insecticide composition is processed into a dosage form selected from the group consisting of: any one of a seed treatment emulsion, an aqueous emulsion, a macrogranule, a microemulsion, a water-soluble granule, a soluble concentrate, a water-dispersible granule, a poison valley, an aerosol, a block poison bait, a sustained-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-in-oil emulsion, an oil-in-water emulsion, a smoke canister, a fine granule, a smoke candle, a smoke canister, a smoke stick, a seed treatment suspension, a smoke tablet, a smoke pellet, a granular poison bait, a hot fogging concentrate, a medicinal paint, a fine granule, an oil suspension, an oil-dispersible powder, a flaky poison bait, a concentrated colloid, a pouring agent, a seed coating 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 suspension, a chasing powder; the plant insect pests controlled by the insecticidal composition are common insect pests in farmlands; the plants controlled by the insecticidal composition are common grain crops and economic crops in agricultural production and horticultural crops.
Example 5: the application of the isothiazole bithiazole amide derivative IV and the bactericide composition in preventing and treating agricultural, forestry and horticultural plant diseases comprises the following steps:
all isothiazole bithiazole amide derivatives IV of the invention are combined with any one or two of commercial bactericides to form a bactericidal composition for preventing and treating agricultural and forestry and horticultural plant diseases, wherein the commercial bactericides are bactericides which are allowed to be registered and used by the agricultural director of China; the total mass percentage of the isothiazole bithiazole amide derivative IV in the sterilization composition is 1-90%, 99-10% of solid or liquid auxiliary agent and optionally 0-25% of surfactant, and the mass percentage of the isothiazole bithiazole amide derivative IV and the commercial bactericide is 1: 99: 1; the bactericidal composition is processed into a dosage form selected from the group consisting of: any one of a seed treatment emulsion, an aqueous emulsion, a macrogranule, a microemulsion, a water-soluble granule, a soluble concentrate, a water-dispersible granule, a poison valley, an aerosol, a block poison bait, a sustained-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-in-oil emulsion, an oil-in-water emulsion, a smoke canister, a fine granule, a smoke candle, a smoke canister, a smoke stick, a seed treatment suspension, a smoke tablet, a smoke pellet, a granular poison bait, a hot fogging concentrate, a medicinal paint, a fine granule, an oil suspension, an oil-dispersible powder, a flaky poison bait, a concentrated colloid, a pouring agent, a seed coating 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 suspension, a chasing powder; the plant diseases controlled by the bactericidal composition are common plant diseases of farmlands; the plants suitable for the sterilizing composition are common grain crops, economic crops and horticultural crops in agricultural production.
Example 6: the application of the isothiazole bithiazole amide derivative IV and the plant virus resisting agent in preventing and treating the virus diseases of agricultural, forestry and horticultural plants is as follows:
all isothiazole bithiazole amide derivatives IV of the invention are combined with any one or two of commercial antiviral medicaments to form an antiviral composition for preventing and treating virus diseases of agricultural, forestry and horticultural plants, and the commercial antiviral medicaments are antiviral medicaments allowed to be registered and used by the agricultural director part in China; the total mass percentage of the isothiazole bithiazole amide derivative IV in the antiviral composition is 1-90%, 99-10% of solid or liquid auxiliary agent and optionally 0-25% of surfactant, and the mass percentage of the isothiazole bithiazole amide derivative IV and the commercial anti-plant virus agent is 1% -99% -1%; the antiviral composition is processed into a dosage form selected from: any one of a seed treatment emulsion, an aqueous emulsion, a macrogranule, a microemulsion, a water-soluble granule, a soluble concentrate, a water-dispersible granule, a poison valley, an aerosol, a block poison bait, a sustained-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-in-oil emulsion, an oil-in-water emulsion, a smoke canister, a fine granule, a smoke candle, a smoke canister, a smoke stick, a seed treatment suspension, a smoke tablet, a smoke pellet, a granular poison bait, a hot fogging concentrate, a medicinal paint, a fine granule, an oil suspension, an oil-dispersible powder, a flaky poison bait, a concentrated colloid, a pouring agent, a seed coating 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 suspension, a chasing powder; the virus diseases controlled by the antiviral composition are plant virus diseases common to farmlands; the plants suitable for the antiviral composition are common grain crops and economic crops in agricultural production and horticultural crops.
Example 7: the application of the isothiazole bithiazole amide derivative IV and acaricide combination in preventing and treating the mite damage of agricultural, forestry and horticultural plants is as follows:
all isothiazole bithiazole amide derivatives IV are combined with any one or two of commercial acaricides to form an acaricidal composition for preventing and controlling the acarid damage of agricultural and forestry and horticultural plants, wherein the commercial acaricides are acaricides which are allowed to be registered in the agricultural director part of China; the total mass percentage of the isothiazole bithiazole amide derivative IV in the acaricidal composition is 1% -90%, 99% -10% of solid or liquid auxiliary agent by weight and optionally 0% -25% of surfactant by weight, and the mass percentage of the isothiazole bithiazole amide derivative IV to the commercial acaricide is 1: 99% -99: 1%; the acaricidal composition is processed into a dosage form selected from the following: any one of a seed treatment emulsion, an aqueous emulsion, a macrogranule, a microemulsion, a water-soluble granule, a soluble concentrate, a water-dispersible granule, a poison valley, an aerosol, a block poison bait, a sustained-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-in-oil emulsion, an oil-in-water emulsion, a smoke canister, a fine granule, a smoke candle, a smoke canister, a smoke stick, a seed treatment suspension, a smoke tablet, a smoke pellet, a granular poison bait, a hot fogging concentrate, a medicinal paint, a fine granule, an oil suspension, an oil-dispersible powder, a flaky poison bait, a concentrated colloid, a pouring agent, a seed coating 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 suspension, a chasing powder; the mite damage prevented and controlled by the mite-killing composition is common plant virus mite damage in farmlands; the acaricidal composition is suitable for plants which are common grain crops and economic crops in agricultural production and horticultural crops.
TABLE 1 chemical Structure and physicochemical parameters of isothiazole-bithiazolamide derivatives IV of the invention
TABLE 2 bacteriostatic activity of isothiazolidinamide derivatives IV of the present invention (inhibition rate of 50. mu.g/ml/%)
| Serial number | Numbering | PI | SS | BC | GZ | CA | AS | RC | PP | PS |
| 1 | ZS-88 | / | / | / | / | / | / | / | / | / |
| 2 | ZS-89 | 5 | 28 | 16 | 3 | 14 | 26 | 24 | 12 | 13 |
| 3 | ZS-90 | 5 | 39 | 55 | 0 | 14 | 6 | 12 | 12 | 13 |
| 4 | ZS-91 | 18 | 36 | 5 | 19 | 17 | 11 | 12 | 12 | 3 |
| 5 | ZS-92 | 16 | 31 | 55 | 16 | 14 | 9 | 37 | 22 | 10 |
| 6 | ZS-93 | 29 | 61 | 48 | 19 | 36 | 34 | 0 | 49 | 27 |
| 7 | ZS-94 | 3 | 66 | 20 | 48 | 29 | 14 | 19 | 20 | 14 |
| 8 | ZS-95 | 3 | 70 | 22 | 38 | 46 | 42 | 38 | 39 | 11 |
| 9 | Isotianil | 3 | 52 | 43 | 10 | 21 | 11 | 62 | 20 | 11 |
| 10 | Thifluzamide | 20 | 91 | 87 | 20 | 90 | 69 | 67 | 69 | 17 |
AS: tomato early blight, its latin name is: alternaria solani, PI: the late blight of potato, its latin name is: phytophthora infestans (Mont.) de Bary, SS: sclerotinia sclerotiorum, its latin name is: sclerotina sclerotiorum, BC: the cucumber botrytis cinerea with the latin name as follows: botrytis cinerea, GZ: wheat scab, its latin name is: gibberella zeae, RC: rhizoctonia cerealis, with the latin name: rhizoctoniacealis, PP: apple ring rot, its latin name is: physiosporia piricola, PS: rhizoctonia solani, the Latin name of which is: pellicularia sasakii, CA: peanut brown spot pathogen, its latin name is: cercosporarachidiacola.
Claims (7)
1. An isothiazole bithiazole amide derivative is characterized by containing isothiazole and thiazole bicyclic groups and having a structural general formula shown in a formula IV:
wherein n is 0, 1, 2, 3, 4; r is selected from: 3-methylphenylethyl, 2-chlorophenylethyl, phenylbutyl, 3-bromophenylmethyl, 1-methylpiperidin-4-yl, 2-ethylmorpholin-4-yl, 4-fluorophenylmethyl.
2. The specific synthetic route and method of isothiazolidineamide derivative IV according to claim 1 is:
the definition of the substituent is as defined in claim 1, and the specific synthetic method comprises the following steps:
A. preparation of compound II:
the intermediate II is prepared by heating, refluxing and stirring the compound I, the thioamino monoethyl ester and a solvent ethanol solution for reaction;
B. isothiazole bithiazole amide derivative IV:
isothiazole bithiazole amide derivative IV prepared from intermediateII and amino substituent, and solvent dichloromethane and acid-binding agent Et3N is prepared by stirring at room temperature, wherein the substituent in the isothiazolebiazolamide derivative IV is defined as in claim 1.
3. Use of isothiazolidinyl bithiazolamide derivatives IV and intermediates thereof as claimed in claim 1 for the preparation of agricultural fungicides.
4. An agricultural fungicidal composition which can be prepared by comprising the isothiazole-bithiazole amide derivative IV of claim 1 and an intermediate thereof, which comprises the isothiazole bithiazole amide derivative IV of claim 1 and an intermediate thereof as an active ingredient in an amount of 0.1 to 99.9% by weight, 99.9 to 0.1% by weight of a solid or liquid adjuvant, and optionally 0 to 25% by weight of a surfactant.
5. An agricultural sterilization compound composition, which comprises the isothiazole bithiazole amide derivative IV and the intermediate thereof as claimed in claim 1 and other commercial bactericides which are compounded to serve as active ingredients, wherein the mass percentage of the isothiazole bithiazole amide derivative IV and the intermediate thereof to the other commercial bactericides is 1 percent to 99 percent to 1 percent, the content of the active ingredients is 1 to 99 percent by weight, and the weight of the active ingredients is 99 to 1 percent of solid or liquid auxiliary agents.
6. An agricultural insecticidal and acaricidal compound composition, which comprises the isothiazole bithiazole amide derivative IV and the intermediate thereof in claim 1 and other commercial insecticidal and acaricidal agents in a compound way to serve as active ingredients, wherein the mass percentage of the isothiazole bithiazole amide derivative IV and the intermediate thereof to other commercial bactericides is 1 to 99 to 1, the content of the active ingredients is 1 to 99 percent by weight, and the weight of the active ingredients is 99 to 1 percent by weight of solid or liquid auxiliaries.
7. A plant activator compound composition comprises the isothiazole bithiazole amide derivative IV and an intermediate thereof as defined in claim 1 and other commercial plant activators as active ingredients, wherein the mass percentage of the isothiazole bithiazole amide derivative IV and the intermediate thereof to other commercial bactericides is 1 to 99 to 1 percent, the content of the active ingredients is 1 to 99 percent by weight, and 99 to 1 percent by weight of solid or liquid auxiliary agents.
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