WO2019001361A1 - 一种胡椒酸衍生物及其制备和应用 - Google Patents

一种胡椒酸衍生物及其制备和应用 Download PDF

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WO2019001361A1
WO2019001361A1 PCT/CN2018/092393 CN2018092393W WO2019001361A1 WO 2019001361 A1 WO2019001361 A1 WO 2019001361A1 CN 2018092393 W CN2018092393 W CN 2018092393W WO 2019001361 A1 WO2019001361 A1 WO 2019001361A1
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formula
compound
halogen
acid derivative
och
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PCT/CN2018/092393
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English (en)
French (fr)
Inventor
吴鸿飞
徐靖博
刘少武
于海波
常秀辉
孙芹
徐利保
程学明
杨浩
孙宁宁
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沈阳中化农药化工研发有限公司
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Priority to BR112019027444-8A priority Critical patent/BR112019027444B1/pt
Priority to US16/625,296 priority patent/US11891371B2/en
Priority to ES18823683T priority patent/ES2909305T3/es
Priority to EP18823683.0A priority patent/EP3647305B1/en
Publication of WO2019001361A1 publication Critical patent/WO2019001361A1/zh

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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D317/00—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms
    • C07D317/08—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3
    • C07D317/44—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3 ortho- or peri-condensed with carbocyclic rings or ring systems
    • C07D317/46—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3 ortho- or peri-condensed with carbocyclic rings or ring systems condensed with one six-membered ring
    • C07D317/48—Methylenedioxybenzenes or hydrogenated methylenedioxybenzenes, unsubstituted on the hetero ring
    • C07D317/62—Methylenedioxybenzenes or hydrogenated methylenedioxybenzenes, unsubstituted on the hetero ring with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to atoms of the carbocyclic ring
    • C07D317/68—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D317/00—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms
    • C07D317/08—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3
    • C07D317/44—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3 ortho- or peri-condensed with carbocyclic rings or ring systems
    • C07D317/46—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3 ortho- or peri-condensed with carbocyclic rings or ring systems condensed with one six-membered ring
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
    • A01N43/00—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds
    • A01N43/02—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with one or more oxygen or sulfur atoms as the only ring hetero atoms
    • A01N43/24—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with one or more oxygen or sulfur atoms as the only ring hetero atoms with two or more hetero atoms
    • A01N43/26—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with one or more oxygen or sulfur atoms as the only ring hetero atoms with two or more hetero atoms five-membered rings
    • A01N43/28—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with one or more oxygen or sulfur atoms as the only ring hetero atoms with two or more hetero atoms five-membered rings with two hetero atoms in positions 1,3
    • A01N43/30—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with one or more oxygen or sulfur atoms as the only ring hetero atoms with two or more hetero atoms five-membered rings with two hetero atoms in positions 1,3 with two oxygen atoms in positions 1,3, condensed with a carbocyclic ring
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01P—BIOCIDAL, PEST REPELLANT, PEST ATTRACTANT OR PLANT GROWTH REGULATORY ACTIVITY OF CHEMICAL COMPOUNDS OR PREPARATIONS
    • A01P3/00—Fungicides
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01P—BIOCIDAL, PEST REPELLANT, PEST ATTRACTANT OR PLANT GROWTH REGULATORY ACTIVITY OF CHEMICAL COMPOUNDS OR PREPARATIONS
    • A01P7/00—Arthropodicides

Definitions

  • the invention belongs to the field of insecticides, acaricides and fungicides, in particular to a piperonic acid derivative and its preparation and application.
  • the corresponding control object After the insecticide, acaricide or bactericide has been used for a period of time, the corresponding control object will be resistant to it, so it is necessary to continuously develop new or improved insecticides, acaricides or fungicides, and compositions thereof. .
  • Structural modification with natural active molecules as a precursor is an important way to discover medicines and pesticides. There are few reports on the discovery of pesticides in pepper as the natural active ingredient, pepper acid.
  • WO2005073165A1 discloses insecticidal compound KC 1 (Compound No. 160 Patent) active against Spodoptera litura and Plutella xylostella were equal to or greater than 70% at a concentration of 100ppm.
  • US8853440B2 discloses a 4-heptafluoroisopropylaniline insecticidal compound KC 2 (English name: Broflanilide, patent number is compound 3-1) and KC 3 (patent number is compound 3-14) at a concentration of 1 ppm. Both Spodoptera litura and Plutella xylostella have activity greater than or equal to 70%.
  • the present invention is based on the natural product, piperonic acid, by introducing an appropriate 4-heptafluoroisopropylaniline active substructure to give a compound of formula I, and obtaining unexpectedly good biological activity results.
  • the pipered acid derivative and its insecticidal, acaricidal and bactericidal activities shown in the present invention have not been reported.
  • a piperonic acid derivative as shown in Formula I:
  • X 1 is selected from halogen
  • X 2 is selected from H or halogen
  • R is selected from H, C 1 -C 3 alkyl or halogenated C 1 -C 3 alkyl
  • Y 1 is selected from halogen or halogenated C 1 -C 3 alkyl
  • Y 2 is selected from halogen or halogenated C 1 -C 3 alkyl.
  • More preferred compounds in the present invention are:
  • X 1 is selected from F, Cl or Br
  • X 2 is selected from H, F, Cl or Br;
  • R is selected from H, methyl or halomethyl
  • Y 1 is selected from the group consisting of F, Cl, Br, I or a halogenated methyl group
  • Y 2 is selected from F, Cl, Br, I or a halomethyl group.
  • X 1 is selected from F
  • X 2 is selected from H or F
  • R is selected from H, methyl or halomethyl
  • Y 1 is selected from the group consisting of F, Cl, Br, I or a halogenated methyl group
  • Y 2 is selected from F, Cl, Br, I or a halomethyl group.
  • Still further preferred compounds of the invention are: Formula I
  • X 1 is selected from F
  • X 2 is selected from F
  • R is selected from H or methyl
  • Y 1 is selected from the group consisting of F, Cl, Br, I or a halogenated methyl group
  • Y 2 is selected from F, Cl, Br, I or a halomethyl group.
  • Still further preferred compounds of the invention are: Formula I
  • X 1 is selected from F
  • X 2 is selected from F
  • R is selected from H or methyl
  • Y 1 is selected from F, Cl, Br or I;
  • Y 2 is selected from F, Cl, Br, I or a halomethyl group.
  • the invention also includes a compound of the formula II,
  • X 1 is selected from halogen
  • X 2 is selected from H or halogen
  • R is selected from H, C 1 -C 3 alkyl or halogenated C 1 -C 3 alkyl
  • LG is selected from C 1 -C 6 alkoxy, OH or halogen.
  • More preferred compounds in the present invention are: in Formula II
  • X 1 is selected from F, Cl or Br
  • X 2 is selected from H, F, Cl or Br;
  • R is selected from H, methyl or halomethyl
  • LG is selected from C 1 -C 6 alkoxy, OH or halogen.
  • X 1 is selected from F
  • X 2 is selected from H or F
  • R is selected from H, methyl or halomethyl
  • LG is selected from C 1 -C 6 alkoxy, OH or halogen.
  • Still further preferred compounds of the invention are: Formula I
  • X 1 is selected from F
  • X 2 is selected from F
  • R is selected from H, methyl
  • LG is selected from C 1 -C 3 alkoxy, OH, F, Cl, Br or I.
  • LG in the compound of the formula II is E(C 1 -C 6 alkoxy) in the formula II-a in the following formula, OH in the formula II-b or in the formula II-c M (halogen) isomerized group.
  • the specific synthesis method is as follows.
  • the compound of the formula III-1 is reacted with a suitable acyl chloride reagent (such as oxalyl chloride and thionyl chloride) to prepare the acid chloride III-2, which is then reacted with a compound of the formula IV (substituted aniline) to give a compound of the formula II-a.
  • a suitable acyl chloride reagent such as oxalyl chloride and thionyl chloride
  • a compound of the formula IV substituted aniline
  • the compound of the formula II-a (substituted benzoate) is hydrolyzed to give the compound of the formula II-b (substituted benzoic acid).
  • the compound of the formula II-b (substituted benzoic acid) is reacted with a suitable acid halide reagent such as oxalyl chloride, thionyl chloride, phosphorus tribromide and phosphorus oxybromide to obtain a compound of the formula II-c (substituted benzene)
  • a suitable acid halide reagent such as oxalyl chloride, thionyl chloride, phosphorus tribromide and phosphorus oxybromide
  • the formyl halide is then reacted with a compound of the formula V (substituted aniline) to give a compound of the formula I.
  • the compound of formula II-a can be directly subjected to an amidolytic reaction with a compound of formula V to provide a compound of formula I.
  • a compound of formula I can be obtained by direct condensation of a compound of formula II-b with a compound of formula V.
  • the compound of the formula III-1 is reacted with a suitable acid chlorinating reagent such as oxalyl chloride and thionyl chloride to prepare an acid chloride, which is then reacted with a compound of the formula VI (substituted aniline) to give a compound of the formula I.
  • a suitable acid chlorinating reagent such as oxalyl chloride and thionyl chloride to prepare an acid chloride, which is then reacted with a compound of the formula VI (substituted aniline) to give a compound of the formula I.
  • Halogen means F, Cl, Br or I.
  • Alkyl a linear, branched or cyclic alkyl group such as methyl, ethyl, n-propyl, isopropyl or cyclopropyl.
  • Haloalkyl a linear, branched or cyclic alkyl group in which a hydrogen atom may be partially or completely substituted by a halogen such as chloromethyl, dichloromethyl, trichloromethyl, fluoromethyl, Difluoromethyl, trifluoromethyl, pentafluoroethyl or heptafluoroisopropyl.
  • a halogen such as chloromethyl, dichloromethyl, trichloromethyl, fluoromethyl, Difluoromethyl, trifluoromethyl, pentafluoroethyl or heptafluoroisopropyl.
  • Alkoxy a linear, branched or cyclic alkoxy group such as methoxy, ethoxy, n-propoxy, isopropoxy, cyclopropyloxy or n-butoxy.
  • Intermediate IV, intermediate V and intermediate VI can be prepared according to the method of US8853440B2.
  • the intermediate III-1, the acid halide reagent, other conventional starting materials and reagents are usually commercially available or can be prepared according to a conventional method.
  • the compound of the formula I is a chirality structural compound due to the difference between X 1 and X 2 , in which case the compound may be a single chiral isomer or a mixture of two chiral isomers.
  • the form of the compound of the formula I to be protected by the present invention is not limited by the form in which the above isomer structure exists.
  • the entire molecule may have a large difference in the transport properties or binding to the receptor in organisms such as insects and plants.
  • the difference in activity will also be large, and the molecular transport properties and suitability for binding to the receptor are unpredictable and require a lot of creative labor to be known.
  • the piperonic acid derivatives (compounds of the formula I) of the invention have unexpectedly high insecticidal activity and high acaricidal activity, and can control the following pests: lepidoptera Pests such as armyworm, beet armyworm and diamondback moth; Homoptera pests such as peach aphid, spider mites and locusts; hemipteran pests such as corn scorpion, tomato scorpion and rice skunk; Target pests such as cotton scorpion horses, thrips and soybeans, etc.; coleopteran pests such as potato beetles and armor; dipteran pests such as flies and mosquitoes; hymenoptera pests such as bees and ants .
  • lepidoptera Pests such as armyworm, beet armyworm and diamondback moth
  • Homoptera pests such as peach aphid, spider mites and locusts
  • hemipteran pests such as corn scorpion, tomato scor
  • the following pests can be controlled: Aphididae (two-spotted spider mites, cinnabar leaf mites, apple whole-clawed scorpion, citrus full-clawed scorpion, etc.), scorpionidae, scorpionidae, and the like. Accordingly, the present invention also encompasses the use of the compounds of formula I for controlling pests and pests in the agricultural, forestry and sanitary fields.
  • the piperonic acid derivative of the present invention has high bactericidal activity and can control the following diseases: rice blast, late blight, gray mold, powdery mildew, anthracnose and downy mildew. Accordingly, the present invention also encompasses the use of the compounds of formula I for the control of diseases in the agricultural, forestry and sanitary fields.
  • the present invention also encompasses a pesticidal, acaricidal and bactericidal composition
  • a pesticidal, acaricidal and bactericidal composition comprising a compound of the above formula I and an agricultural, forestry or sanitary neighborhood acceptable carrier;
  • the compound is shown as the active ingredient, and the active ingredient is present in the composition in an amount of from 0.1 to 99% by weight.
  • the composition may include a compound of the above formula I in the form of a heterostructure.
  • the composition may be used in the form of a dry powder, a wettable powder, an emulsifiable concentrate, a microemulsion, a paste, a granule, a solution, a suspending agent, etc., and the choice of the type of the composition depends on the particular application.
  • compositions are prepared in a known manner, for example by diluting or dissolving the active substance with a solvent medium and/or a solid diluent, optionally in the presence of a surfactant.
  • Useful solid diluents or carriers can be silica, kaolin, bentonite, talc, diatomaceous earth, dolomite, calcium carbonate, magnesia, chalk, clay, synthetic silicates, attapulgite, sepiolite, and the like.
  • useful liquid diluents are aromatic organic solvents (mixtures of xylene or alkylbenzenes, chlorobenzene, etc.), paraffins (petroleum fractions), alcohols (methanol, propanol, butanol, octanol, glycerol). ), esters (ethyl acetate, isobutyl acetate, etc.), ketones (cyclohexanone, acetone, acetophenone, isophorone, ethyl amyl ketone, etc.), amides (N, N-II) Methylformamide, N-methylpyrrolidone, etc.).
  • Usable surfactants are alkyl sulfonates, alkyl aryl sulfonates, alkyl phenol ethoxylates, polyoxyethylene sorbitan fatty acid esters, lignosulfonates and the like.
  • compositions may also contain special additives for specific purposes such as binders such as gum arabic, polyvinyl alcohol, polyvinylpyrrolidone and the like.
  • the concentration of the active ingredient in the above composition may vary within a wide range depending on the active ingredient, its intended use, environmental conditions, and the type of preparation employed. Generally, the concentration of the active ingredient ranges from 1 to 90%, preferably from 5 to 50%.
  • the technical solution of the present invention also includes a method of controlling pests by applying the pesticidal composition of the present invention to the pest or the growth medium thereof.
  • a more suitable effective amount is usually selected from 10 grams to 1000 grams per hectare, preferably from 20 grams to 500 grams per hectare.
  • the technical solution of the present invention also includes a method of controlling pests by applying the pesticidal composition of the present invention to the pest or the growth medium thereof.
  • a more suitable effective amount is usually selected from 10 grams to 1000 grams per hectare, preferably from 20 grams to 500 grams per hectare.
  • the technical solution of the present invention also includes a method of controlling a disease by applying the pesticidal composition of the present invention to the disease or its growth medium.
  • a more suitable effective amount is usually selected from 10 grams to 1000 grams per hectare, preferably from 20 grams to 500 grams per hectare.
  • the addition of one or more other fungicides, insecticides, acaricides, herbicides, plant growth regulators to the pesticidal, acaricidal and bactericidal compositions of the present invention Or fertilizers, etc. can produce additional advantages and effects.
  • the invention adopts the natural product piperonic acid as the lead, and obtains the compound of the general formula I by introducing an appropriate 4-heptafluoroisopropylaniline active substructure, and the opportunity of interaction and binding between the molecule and the receptor is enhanced by introducing a new structure.
  • the unexpectedly good biological activity results in insecticidal, acaricidal and bactericidal activities are obtained, so that the piperonic acid derivative obtained by the present invention has more comprehensive biological properties.
  • reaction solution was cooled to room temperature, and the insoluble material was filtered and evaporated, and ethyl acetate (100 mL) was added, and the mixture was washed with saturated aqueous sodium hydrogencarbonate and brine, and the organic phase was separated. The organic solvent was evaporated under reduced pressure, and the residue was purified mjjjjjj ).
  • reaction solution was cooled to room temperature, stirred well, and the solid was gradually precipitated, filtered, and the filter cake was purified by column chromatography to give the title compound as a white solid (0.57 g, yield: 84% (N-(2-bromo-6-trifluoro) -4--4-heptafluoroisopropylphenyl)-2-fluoro-3-methylaminobenzamide.
  • reaction solution was cooled to room temperature, stirred well, and the solid was gradually precipitated, filtered, and the filter cake was separated and purified by column chromatography to give the title compound as a white solid, 0.55 g, yield 83% (N-(2-bromo-6-trifluoromethyl) Based on -4-heptafluoroisopropylphenyl)-2-fluoro-3-aminobenzamide.
  • the reaction solution was cooled to room temperature, and the insoluble material was filtered out, and the acetonitrile was evaporated under reduced pressure, and ethyl acetate (30 mL) was added to dissolve, and the mixture was washed successively with saturated aqueous sodium hydrogen carbonate and brine, and the organic phase was separated. After drying over magnesium sulfate, the organic solvent was evaporated, evaporated, evaporated, mjjjjjjjjjjjjj Aniline meter).
  • reaction solution was cooled to room temperature, stirred well, and the solid was gradually precipitated, and filtered, and the filter cake was purified by column chromatography to give the title compound as a white solid, 0.60 g, melting point: 157-158 ° C, yield 87% (N-(2, 6-Dibromo-4-heptafluoroisopropylphenyl)-2-fluoro-3-methylaminobenzamide.
  • the ethyl 2-fluoro-3-aminobenzamide (0.51 g, 0.9 mmol) was warmed to 110 ° C and was then taken to work.
  • the reaction solution was cooled to room temperature, stirred well, and the solid was gradually precipitated, and filtered, and the filter cake was purified by column chromatography to give the title compound as a white solid, 0.54 g, melting point: 176-177 ° C, yield 80% (N-(2, 6-Dibromo-4-heptafluoroisopropylphenyl)-2-fluoro-3-aminobenzamide.
  • the solubility of the test compound is dissolved in acetone or dimethyl sulfoxide, and then formulated into a desired concentration of 50 ml of the test solution with 0.1% Tween 80 solution, acetone or dimethyl sulfoxide in the total solution.
  • the content does not exceed 10% and is ready for use.
  • the middle leaves of fresh corn were cut into 3 cm sections, and immersed in the prepared liquid for 10 seconds. After being dried in the shade, they were placed in a petri dish with a filter paper of 9 cm in diameter, and the healthy test insects were connected. 3 years old), 14 treatments per treatment, 4 trials were repeated, and the water treatment was set as a blank control. After the treatment, the cells were cultured at 24 ° C, relative humidity of 60% - 70%, and natural light. After 72 hours, the number of viable animals was investigated, and the mortality was calculated.
  • Table 1 Parallel determination results of compound I-8, I-51, KC 1 and KC 3 against armyworm activity (mortality, %)
  • the cabbage leaves cultured at room temperature were selected, the surface wax layer was removed, and a circular disc with a diameter of 2 cm was punched with a puncher, and immersed in the prepared liquid for 10 seconds, dried and placed on a filter paper.
  • a petri dish with a diameter of 9 cm a neat healthy test insect (2 years old) was inserted, and each treatment was carried out for 10 times.
  • the test was set to repeat 4 times, and the water treatment was set as a blank control. After the treatment, the cells were cultured at 24 ° C, relative humidity of 60% - 70%, and natural light. After 72 hours, the number of surviving insects was investigated, and the mortality was calculated.
  • the cabbage leaves were punched into a 1 cm diameter leaf disc with a puncher and sprayed with a hand-held Airbrush. A certain concentration of the test compound was sprayed on the front and back of each leaf disc. The amount of liquid sprayed was 0.5 ml.
  • the test was set to repeat 3 times, and the water treatment was set as a blank control. After the treatment, the cells were cultured at 24 ° C, relative humidity of 60% - 70%, and without light, and the number of viable animals was investigated after 96 hours to calculate the mortality.
  • the results of parallel determination of the activities of Compound I-8 and KC 2 (Compound 3-1 in US8853440B2) on Spodoptera exigua are shown in Table 2.
  • compounds I-8 and I-51 had better control effects against peach aphid at a concentration of 10 mg/L, and the mortality rate was above 80%.
  • test compound A certain concentration of test compound was sprayed on the page at the peak of hatching of rice leaf roller, with a spray volume of 450 liters per hectare.
  • the rice plot has an area of 32 square meters and is repeated three times. The number of viable animals was investigated 15 days later and the mortality was calculated.
  • the results of parallel determination of the activities of Compounds I-8 and KC 2 against Cnaphalocrocis medinalis are shown in Table 3.
  • Table 3 Parallel determination of the activity of compound I-8 and KC 2 on rice leaf roller (mortality, %)
  • the solubility of the test compound is dissolved in acetone or dimethyl sulfoxide, and then formulated into a desired concentration of 50 ml of the test solution with 0.1% Tween 80 solution, acetone or dimethyl sulfoxide in the total solution.
  • the content does not exceed 10%.
  • control compounds C 1 and C 2 are the non-listed compounds included in the scope of the disclosure of the patent AU2004315003B2.
  • the parallel determination results of the activities of the compounds I-8, KC 1 , KC 2 , KC 3 , C 1 and C 2 on the mites of T. cinnabarinus are shown in Table 5.
  • Table 4 Parallel determination of the activity of compounds I-8, KC 1 , KC 2 , KC 3 , C 1 and C 2 on the mites of T. cinnabarinus (mortality, %)
  • the 3rd instar larvae were tested by the mixed drug method.
  • the acetone solution of 1000mg/L of the test compound was diluted to the required concentration with a certain concentration of milk powder solution according to the experimental design dose, and then mixed with a pipetting gun.
  • the toxic milk powder solution was evenly added to a petri dish with a diameter of 6 cm and a filter paper, and 1 ml of each dish was placed in the Petri dish.
  • the test was set up in 3 replicates, placed in a standard observation room after treatment, and investigated after 72 hours. The number of surviving animals was calculated and the mortality was calculated.
  • Table 6 The results of parallel determination of the activity of Compound I-51 and KC 2 against Musca domestica larvae are shown in Table 6.
  • the test compound According to the solubility of the test compound, it is dissolved in acetone, methanol or DMF, and then prepared with 0.1% Tween 80 solution to prepare the desired concentration of 50 ml of the test solution, the content of acetone or dimethyl sulfoxide in the total solution. No more than 5%.
  • the two-leaf cucumber seedlings with uniform growth were selected and sprayed with a certain concentration of test compound.
  • the cucumber downy mildew spore suspension was inoculated and then placed in an artificial climate chamber. After the disease was infested, it was transferred to the greenhouse. After 5 days, according to the incidence of the blank control, the control effect was investigated by visual inspection. The control effect was recorded with 100%-0, 100% indicating no disease, and 0 indicating that the degree of treatment was comparable to the blank control.
  • Compounds I-8 and I-51 were more than 90% effective against cucumber downy mildew at a concentration of 400 mg/L.

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Abstract

一种胡椒酸衍生物及其制备和应用。结构如通式I所示。通式I化合物具有优异的杀虫、杀螨和杀菌活性，可用于防治各种害虫、害螨或有害病菌。

Description

一种胡椒酸衍生物及其制备和应用 技术领域
本发明属于杀虫剂、杀螨剂和杀菌剂领域，具体涉及一种胡椒酸衍生物及其制备和应用。
背景技术
杀虫剂、杀螨剂或杀菌剂在使用一段时间后，对应的防治对象会对其产生抗性，所以需要不断研发新型或改进的杀虫剂、杀螨剂或杀菌剂，及其组合物。
以天然活性分子为先导进行结构修饰是医药和农药发现的一种重要途径。胡椒中天然活性成分胡椒酸作为先导进行农药发现研究报道较少。
WO2005073165A1、US2007275980A1和US20140206727A1公开了杀虫化合物KC 1(专利编号为化合物160)在100ppm浓度下对斜纹夜蛾和小菜蛾的活性均大于或等于70％。
Figure PCTCN2018092393-appb-000001
US8853440B2公开了含4-七氟异丙基苯胺类杀虫化合物KC 2(英文通用名：Broflanilide，专利编号为化合物3-1)和KC 3(专利编号为化合物3-14)在1ppm浓度下对斜纹夜蛾和小菜蛾的活性均大于或等于70％。
Figure PCTCN2018092393-appb-000002
本发明以天然产物胡椒酸为先导，通过引入适当的4-七氟异丙基苯胺类活性亚结构得到通式I化合物，并获得了意外好的生物活性结果。本发明所示的胡椒酸衍生物及其杀虫、杀螨剂和杀菌活性未见报道。
发明内容
本发明的目的在于提供一种胡椒酸衍生物及其制备和作为杀虫剂、杀螨剂和杀菌剂的应用。
为实现上述目的，本发明的技术方案如下：
一种胡椒酸衍生物，如通式I所示：
Figure PCTCN2018092393-appb-000003
式中：
X 1选自卤素；
X 2选自H或卤素；
R选自H、C 1-C 3烷基或卤代C 1-C 3烷基；
Y 1选自卤素或卤代C 1-C 3烷基；
Y 2选自卤素或卤代C 1-C 3烷基。
本发明中较优选的化合物为：通式I中
X 1选自F、Cl或Br；
X 2选自H、F、Cl或Br；
R选自H、甲基或卤代甲基；
Y 1选自F、Cl、Br、I或卤代甲基；
Y 2选自F、Cl、Br、I或卤代甲基。
本发明中进一步优选的化合物为：通式I中
X 1选自F；
X 2选自H或F；
R选自H、甲基或卤代甲基；
Y 1选自F、Cl、Br、I或卤代甲基；
Y 2选自F、Cl、Br、I或卤代甲基。
本发明中再进一步优选的化合物为：通式I中
X 1选自F；
X 2选自F；
R选自H或甲基；
Y 1选自F、Cl、Br、I或卤代甲基；
Y 2选自F、Cl、Br、I或卤代甲基。
本发明中又进一步优选的化合物为：通式I中
X 1选自F；
X 2选自F；
R选自H或甲基；
Y 1选自F、Cl、Br或I；
Y 2选自F、Cl、Br、I或卤代甲基。
本发明还包括一种通式II所示化合物，
Figure PCTCN2018092393-appb-000004
式中：
X 1选自卤素；
X 2选自H或卤素；
R选自H、C 1-C 3烷基或卤代C 1-C 3烷基；
LG选自C 1-C 6烷氧基、OH或卤素。
本发明中较优选的化合物为：通式II中
X 1选自F、Cl或Br；
X 2选自H、F、Cl或Br；
R选自H、甲基或卤代甲基；
LG选自C 1-C 6烷氧基、OH或卤素。
本发明中进一步优选的化合物为：通式II中
X 1选自F；
X 2选自H或F；
R选自H、甲基或卤代甲基；
LG选自C 1-C 6烷氧基、OH或卤素。
本发明中再进一步优选的化合物为：通式I中
X 1选自F；
X 2选自F；
R选自H、甲基；
LG选自C 1-C 3烷氧基、OH、F、Cl、Br或I。
本发明的通式I化合物可按照以下方法制备，除另有注明外，式中各基团的定义同前。方法一
Figure PCTCN2018092393-appb-000005
式中，通式II化合物中的LG为下式中的通式II-a中的E(C 1-C 6烷氧基)、通式II-b中的OH或通式II-c中的M(卤素)等离去基团。具体合成方法如下，
Figure PCTCN2018092393-appb-000006
通式III-1化合物与适宜的酰氯化试剂(如草酰氯和氯化亚砜等)反应制备酰氯III-2，再与通式IV化合物(取代苯胺)反应制得通式II-a化合物。通式II-a化合物(取代苯甲酸酯)水解得通式II-b化合物(取代苯甲酸)。通式II-b化合物(取代苯甲酸)与适宜的酰卤化试剂(如草酰氯、氯化亚砜、三溴化磷和三溴氧磷等)反应制得通式II-c化合物(取代苯甲酰卤)，再与通式V化合物(取代苯胺)反应制得通式I化合物。
或者通式II-a化合物与通式V化合物进行胺解反应直接制得通式I化合物。
或者通式II-b化合物与通式V化合物直接缩合制得通式I化合物。
方法二
Figure PCTCN2018092393-appb-000007
通式III-1化合物与适宜的酰氯化试剂(如草酰氯和氯化亚砜等)反应制备酰氯，再与通式VI化合物(取代苯胺)反应制得通式I化合物。
上面给出的通式化合物的定义中，汇集所用术语一般代表如下取代基：
卤素：指F、Cl、Br或I。
烷基：直链、支链或环状烷基，例如甲基、乙基、正丙基、异丙基或环丙基等。
卤代烷基：直链、支链或环状烷基，在这些烷基上的氢原子可部分或全部被卤素所取代，例如氯甲基、二氯甲基、三氯甲基、氟甲基、二氟甲基、三氟甲基、五氟乙基或七氟异丙基等。
烷氧基：直链、支链或环状烷氧基，例如甲氧基、乙氧基、正丙氧基、异丙氧基、环丙基氧基或正丁氧基等。
上述制备方法中所涉及的原料及中间体来源如下：
中间体IV、中间体V和中间体VI可以按US8853440B2方法制备。
中间体III-1、酰卤化试剂、其它常规原料和试剂通常有市售，也可按照常规方法自制。
在本发明的化合物中，由于X 1和X 2的不同，通式I化合物是手性(chirality)结构化合物，此时，化合物可以以单一手性异构体或两种手性异构体混合形式存在，本发明所要保护的通式I所示化合物并不受上述异构体结构存在形式限定。
表1中列出的具体化合物可以用来说明本发明，但并不限定本发明。
表1
Figure PCTCN2018092393-appb-000008
编号 X 1 X 2 R Y 1 Y 2
I-1 F F H I I
I-2 F F H Br CF 3
I-3 F F H Cl Cl
I-4 F F H F F
I-5 F F H Br I
I-6 F F H Br Cl
I-7 F F H Br F
I-8 F F H Br Br
I-9 F F H I Cl
I-10 F F H F Cl
I-11 F F H F I
I-12 F F H F CF 3
I-13 F F H Cl CF 3
I-14 F F H I CF 3
I-15 F F H CF 3 CF 3
I-16 F F H F CF 2CF 3
I-17 F F H F CF(CF 3) 2
I-18 F F H Br CF 2CF 3
I-19 F F H Br CF(CF 3) 2
I-20 F F H Cl CF 2CF 3
I-21 F F H Cl CF(CF 3) 2
I-22 F F H I CF 2CF 3
I-23 F F H I CF(CF 3) 2
I-24 F F H F CHF 2
I-25 F F H Cl CHF 2
I-26 F F H I CHF 2
I-27 F F H Br CHF 2
I-28 F F H F CH 2F
I-29 F F H Cl CH 2F
I-30 F F H I CH 2F
I-31 F F H Br CH 2F
I-32 F F H F CH 2Cl
I-33 F F H Cl CH 2Cl
I-34 F F H I CH 2Cl
I-35 F F H Br CH 2Cl
I-36 F F H F CH 2Br
I-37 F F H Cl CH 2Br
I-38 F F H I CH 2Br
I-39 F F H Br CH 2Br
I-40 F F H F CH 2I
I-41 F F H Cl CH 2I
I-42 F F H I CH 2I
I-43 F F H Br CH 2I
I-44 F F CH 3 I I
I-45 F F CH 3 Br CF 3
I-46 F F CH 3 Cl Cl
I-47 F F CH 3 F F
I-48 F F CH 3 Br I
I-49 F F CH 3 Br Cl
I-50 F F CH 3 Br F
I-51 F F CH 3 Br Br
I-52 F F CH 3 I Cl
I-53 F F CH 3 F Cl
I-54 F F CH 3 F I
I-55 F F CH 3 F CF 3
I-56 F F CH 3 Cl CF 3
I-57 F F CH 3 I CF 3
I-58 F F CH 3 CF 3 CF 3
I-59 F F CH 3 F CF 2CF 3
I-60 F F CH 3 F CF(CF 3) 2
I-61 F F CH 3 Br CF 2CF 3
I-62 F F CH 3 Br CF(CF 3) 2
I-63 F F CH 3 Cl CF 2CF 3
I-64 F F CH 3 Cl CF(CF 3) 2
I-65 F F CH 3 I CF 2CF 3
I-66 F F CH 3 I CF(CF 3) 2
I-67 F F CH 3 F CHF 2
I-68 F F CH 3 Cl CHF 2
I-69 F F CH 3 I CHF 2
I-70 F F CH 3 Br CHF 2
I-71 F F CH 3 F CH 2F
I-72 F F CH 3 Cl CH 2F
I-73 F F CH 3 I CH 2F
I-74 F F CH 3 Br CH 2F
I-75 F F CH 3 F CH 2Cl
I-76 F F CH 3 Cl CH 2Cl
I-77 F F CH 3 I CH 2Cl
I-78 F F CH 3 Br CH 2Cl
I-79 F F CH 3 F CH 2Br
I-80 F F CH 3 Cl CH 2Br
I-81 F F CH 3 I CH 2Br
I-82 F F CH 3 Br CH 2Br
I-83 F F CH 3 F CH 2I
I-84 F F CH 3 Cl CH 2I
I-85 F F CH 3 I CH 2I
I-86 F F CH 3 Br CH 2I
I-87 Cl Cl H I I
I-88 Cl Cl H Br CF 3
I-89 Cl Cl H Cl Cl
I-90 Cl Cl H F F
I-91 Cl Cl H Br I
I-92 Cl Cl H Br Cl
I-93 Cl Cl H Br F
I-94 Cl Cl H Br Br
I-95 Cl Cl H I Cl
I-96 Cl Cl H F Cl
I-97 Cl Cl H F I
I-98 Cl Cl H F CF 3
I-99 Cl Cl H Cl CF 3
I-100 Cl Cl H I CF 3
I-101 Cl Cl H CF 3 CF 3
I-102 Cl Cl H F CF 2CF 3
I-103 Cl Cl H F CF(CF 3) 2
I-104 Cl Cl H Br CF 2CF 3
I-105 Cl Cl H Br CF(CF 3) 2
I-106 Cl Cl H Cl CF 2CF 3
I-107 Cl Cl H Cl CF(CF 3) 2
I-108 Cl Cl H I CF 2CF 3
I-109 Cl Cl H I CF(CF 3) 2
I-110 Cl Cl H F CHF 2
I-111 Cl Cl H Cl CHF 2
I-112 Cl Cl H I CHF 2
I-113 Cl Cl H Br CHF 2
I-114 Cl Cl H F CH 2F
I-115 Cl Cl H Cl CH 2F
I-116 Cl Cl H I CH 2F
I-117 Cl Cl H Br CH 2F
I-118 Cl Cl H F CH 2Cl
I-119 Cl Cl H Cl CH 2Cl
I-120 Cl Cl H I CH 2Cl
I-121 Cl Cl H Br CH 2Cl
I-122 Cl Cl H F CH 2Br
I-123 Cl Cl H Cl CH 2Br
I-124 Cl Cl H I CH 2Br
I-125 Cl Cl H Br CH 2Br
I-126 Cl Cl H F CH 2I
I-127 Cl Cl H Cl CH 2I
I-128 Cl Cl H I CH 2I
I-129 Cl Cl H Br CH 2I
I-130 Cl Cl CH 3 I I
I-131 Cl Cl CH 3 Br CF 3
I-132 Cl Cl CH 3 Cl Cl
I-133 Cl Cl CH 3 F F
I-134 Cl Cl CH 3 Br I
I-135 Cl Cl CH 3 Br Cl
I-136 Cl Cl CH 3 Br F
I-137 Cl Cl CH 3 Br Br
I-138 Cl Cl CH 3 I Cl
I-139 Cl Cl CH 3 F Cl
I-140 Cl Cl CH 3 F I
I-141 Cl Cl CH 3 F CF 3
I-142 Cl Cl CH 3 Cl CF 3
I-143 Cl Cl CH 3 I CF 3
I-144 Cl Cl CH 3 CF 3 CF 3
I-145 Cl Cl CH 3 F CF 2CF 3
I-146 Cl Cl CH 3 F CF(CF 3) 2
I-147 Cl Cl CH 3 Br CF 2CF 3
I-148 Cl Cl CH 3 Br CF(CF 3) 2
I-149 Cl Cl CH 3 Cl CF 2CF 3
I-150 Cl Cl CH 3 Cl CF(CF 3) 2
I-151 Cl Cl CH 3 I CF 2CF 3
I-152 Cl Cl CH 3 I CF(CF 3) 2
I-153 Cl Cl CH 3 F CHF 2
I-154 Cl Cl CH 3 Cl CHF 2
I-155 Cl Cl CH 3 I CHF 2
I-156 Cl Cl CH 3 Br CHF 2
I-157 Cl Cl CH 3 F CH 2F
I-158 Cl Cl CH 3 Cl CH 2F
I-159 Cl Cl CH 3 I CH 2F
I-160 Cl Cl CH 3 Br CH 2F
I-161 Cl Cl CH 3 F CH 2Cl
I-162 Cl Cl CH 3 Cl CH 2Cl
I-163 Cl Cl CH 3 I CH 2Cl
I-164 Cl Cl CH 3 Br CH 2Cl
I-165 Cl Cl CH 3 F CH 2Br
I-166 Cl Cl CH 3 Cl CH 2Br
I-167 Cl Cl CH 3 I CH 2Br
I-168 Cl Cl CH 3 Br CH 2Br
I-169 Cl Cl CH 3 F CH 2I
I-170 Cl Cl CH 3 Cl CH 2I
I-171 Cl Cl CH 3 I CH 2I
I-172 Cl Cl CH 3 Br CH 2I
I-173 F H H Br CF 3
I-174 F H H Br I
I-175 F H H Br Br
I-176 F H H Br Cl
I-177 F H CH 3 Br CF 3
I-178 F H CH 3 Br I
I-179 F H CH 3 Br Br
I-180 F H CH 3 Br Cl
I-181 F H H Cl Cl
I-182 F H CH 3 F F
I-183 F H CH 3 I I
I-184 F H H Cl CF 3
I-185 Br Br H Br CF 3
I-186 Br Br H Br I
I-187 Br Br H Br Br
I-188 Br Br H Br Cl
I-189 Br Br CH 3 Br CF 3
I-190 Br Br CH 3 Br I
I-191 Br Br CH 3 Br Br
I-192 Br Br CH 3 Br Cl
I-193 Br Br H Cl Cl
I-194 Br Br CH 3 F F
I-195 Br Br CH 3 I I
I-196 Br Br H Cl CF 3
I-197 I I H Cl CF 3
I-198 I I H CF 3 CF 3
I-199 I I H Br CF 3
I-200 I I H Br Br
I-201 I I H Br I
I-202 I I H F Br
I-203 I I H F CF 3
I-204 I I H Cl Br
部分化合物的 1H NMR(300MHz，CDCl 3，ppm)及物化性质如下：
Figure PCTCN2018092393-appb-000009
同时，表2中列出的具体化合物为上述制备方法一反应式中通式II化合物，其可以用来说明本发明，但并不限定本发明。
表2
Figure PCTCN2018092393-appb-000010
Figure PCTCN2018092393-appb-000011
编号 X 1 X 2 R LG
II-1 F F H OCH 3
II-2 F F H OCH 2CH 3
II-3 F F H OCH 2CH 2CH 3
II-4 F F H OCH(CH 3) 2
II-5 F F H OCH 2CH 2CH 2CH 3
II-6 F F H OC(CH 3) 3
II-7 F F H OH
II-8 F F H F
II-9 F F H Cl
II-10 F F H Br
II-11 F F H I
II-12 F F CH 3 OCH 3
II-13 F F CH 3 OCH 2CH 3
II-14 F F CH 3 OCH 2CH 2CH 3
II-15 F F CH 3 OCH(CH 3) 2
II-16 F F CH 3 OCH 2CH 2CH 2CH 3
II-17 F F CH 3 OC(CH 3) 3
II-18 F F CH 3 OH
II-19 F F CH 3 F
II-20 F F CH 3 Cl
II-21 F F CH 3 Br
II-22 F F CH 3 I
II-23 F H H OCH 3
II-24 F H H OCH 2CH 3
II-25 F H H OCH 2CH 2CH 3
II-26 F H H OCH(CH 3) 2
II-27 F H H OCH 2CH 2CH 2CH 3
II-28 F H H OC(CH 3) 3
II-29 F H H OH
II-30 F H H F
II-31 F H H Cl
II-32 F H H Br
II-33 F H H I
II-34 F H CH 3 OCH 3
II-35 F H CH 3 OCH 2CH 3
II-36 F H CH 3 OCH 2CH 2CH 3
II-37 F H CH 3 OCH(CH 3) 2
II-38 F H CH 3 OCH 2CH 2CH 2CH 3
II-39 F H CH 3 OC(CH 3) 3
II-40 F H CH 3 OH
II-41 F H CH 3 F
II-42 F H CH 3 Cl
II-43 F H CH 3 Br
II-44 F H CH 3 I
II-45 Cl Cl H OCH 3
II-46 Cl Cl H OCH 2CH 3
II-47 Cl Cl H OCH 2CH 2CH 3
II-48 Cl Cl H OCH(CH 3) 2
II-49 Cl Cl H OCH 2CH 2CH 2CH 3
II-50 Cl Cl H OC(CH 3) 3
II-51 Cl Cl H OH
II-52 Cl Cl H F
II-53 Cl Cl H Cl
II-54 Cl Cl H Br
II-55 Cl Cl H I
II-56 Cl Cl CH 3 OCH 3
II-57 Cl Cl CH 3 OCH 2CH 3
II-58 Cl Cl CH 3 OCH 2CH 2CH 3
II-59 Cl Cl CH 3 OCH(CH 3) 2
II-60 Cl Cl CH 3 OCH 2CH 2CH 2CH 3
II-61 Cl Cl CH 3 OC(CH 3) 3
II-62 Cl Cl CH 3 OH
II-63 Cl Cl CH 3 F
II-64 Cl Cl CH 3 Cl
II-65 Cl Cl CH 3 Br
II-66 Cl Cl CH 3 I
II-67 Br Br H OCH 3
II-68 Br Br H OCH 2CH 3
II-69 Br Br H OCH 2CH 2CH 3
II-70 Br Br H OCH(CH 3) 2
II-71 Br Br H OCH 2CH 2CH 2CH 3
II-72 Br Br H OC(CH 3) 3
II-73 Br Br H OH
II-74 Br Br H F
II-75 Br Br H Cl
II-76 Br Br H Br
II-77 Br Br H I
II-78 Br Br CH 3 OCH 3
II-79 Br Br CH 3 OCH 2CH 3
II-80 Br Br CH 3 OCH 2CH 2CH 3
II-81 Br Br CH 3 OCH(CH 3) 2
II-82 Br Br CH 3 OCH 2CH 2CH 2CH 3
II-83 Br Br CH 3 OC(CH 3) 3
II-84 Br Br CH 3 OH
II-85 Br Br CH 3 F
II-86 Br Br CH 3 Cl
II-87 Br Br CH 3 Br
II-88 Br Br CH 3 I
II-89 I I H OCH 3
II-90 I I H OCH 2CH 3
II-91 I I H OCH 2CH 2CH 3
II-92 I I H OCH(CH 3) 2
II-93 I I H OCH 2CH 2CH 2CH 3
II-94 I I H OC(CH 3) 3
II-95 I I H OH
II-96 I I H F
II-97 I I H Cl
II-98 I I H Br
II-99 I I H I
II-100 I I CH 3 OCH 3
II-101 I I CH 3 OCH 2CH 3
II-102 I I CH 3 OCH 2CH 2CH 3
II-103 I I CH 3 OCH(CH 3) 2
II-104 I I CH 3 OCH 2CH 2CH 2CH 3
II-105 I I CH 3 OC(CH 3) 3
II-106 I I CH 3 OH
II-107 I I CH 3 F
II-108 I I CH 3 Cl
II-109 I I CH 3 Br
部分化合物的 1H NMR(300MHz,CDCl 3,ppm)及物化性质如下：
Figure PCTCN2018092393-appb-000012
在有机分子中，由于取代基的电负性、体积大小或空间构型的不同，整个分子在昆虫和植物等生物体内的输导性能或与受体结合差异性会很大，表现出的生物活性差异也会有很大，而分子的输导性能和与受体结合的合适性是不可预测的，需要大量的创造性劳动才能获知。
同已知化合物KC 1、KC 2或KC 3相比，本发明的胡椒酸衍生物(通式I化合物)具有意想不到的高杀虫活性和高杀螨活性，可以防治如下害虫：鳞翅目害虫，如粘虫、甜菜夜蛾和小菜蛾等；同翅目害虫，如桃蚜、叶婵和飞虱等；半翅目害虫，如玉米长蝽、番茄盲蝽和稻臭椿等；缨翅目害虫，如棉蓟马、苜蓿蓟马和黄豆蓟马等；鞘翅目害虫，如马铃薯甲虫和叩甲等；双翅目害虫，如蝇和蚊等；膜翅目害虫，如蜂和蚁等。可以防治如下害螨：叶螨科(二斑叶螨、朱砂叶螨、苹果全爪螨、柑橘全爪螨等)、瘿螨科、跗线螨科等。因此，本发明还包括通 式I化合物用于农业、林业及卫生领域中控制虫害和螨害的用途。
本发明的胡椒酸衍生物具有高杀菌活性，可以控制如下病害：稻瘟病、晚疫病、灰霉病、白粉病、炭疽病和霜霉病等。因此，本发明还包括通式I化合物用于农业、林业及卫生领域中控制病害的用途。
本发明还包括一种杀虫、杀螨和杀菌组合物，所述组合物中含上述通式I所示化合物和农业、林业或卫生邻域上可接受的载体；以所述通式I所示化合物为活性组分，所述组合物中活性组分的重量百分含量为0.1-99％。所述组合物可包括各异体结构存在形式的上述通式I所示的化合物。
组合物的使用形式可以是干粉、可湿性粉剂、乳油、微乳剂、糊剂、颗粒剂、溶液、悬浮剂等，组合物类型的选择取决于具体的应用。
组合物是以已知方式制备的，例如任选在表面活性剂的存在下，通过用溶剂介质和/或固体稀释剂稀释或溶解活性物质。
可用的固体稀释剂或载体可以是二氧化硅、高岭土、膨润土、滑石、硅藻土、白云石、碳酸钙、氧化镁、白垩、粘土、合成硅酸盐、硅镁土、海泡石等。
除水以外，可用的液体稀释剂是芳族有机溶剂(二甲苯或烷基苯的混合物、氯苯等)、石蜡(石油馏分)、醇类(甲醇、丙醇、丁醇、辛醇、甘油)、酯类(乙酸乙酯、乙酸异丁酯等)、酮类(环己酮、丙酮、苯乙酮、异佛尔酮、乙基戊基酮等)、酰胺类(N,N-二甲基甲酰胺、N-甲基吡咯烷酮等)。
可用的表面活性剂是烷基磺酸盐、烷基芳基磺酸盐、烷基酚聚氧乙烯醚、聚氧乙烯山梨醇脂肪酸酯、木质素磺酸盐等。
组合物还可含特殊的添加剂用于特定的目的，例如粘合剂如阿拉伯胶、聚乙烯醇、聚乙烯吡咯烷酮等。
上述组合物中活性成分的浓度可根据活性成分、其使用目的、环境条件和采用的制剂类型而在较宽范围内改变。通常，活性成分的浓度范围是1-90％，优选5-50％。
本发明的技术方案还包括防治害虫的方法：将本发明的杀虫组合物施于所述的害虫或其生长介质上。通常选择的较为适宜有效量为每公顷10克到1000克，优选有效量为每公顷20克到500克。
本发明的技术方案还包括防治害螨的方法：将本发明的杀虫组合物施于所述的害螨或其生长介质上。通常选择的较为适宜有效量为每公顷10克到1000克，优选有效量为每公顷20克到500克。
本发明的技术方案还包括防治病害的方法：将本发明的杀虫组合物施于所述的病害或其生长介质上。通常选择的较为适宜有效量为每公顷10克到1000克，优选有效量为每公顷20克到500克。
对于某些应用，如在农业上，在本发明的杀虫、杀螨和杀菌组合物中加入一种或多种其它的杀菌剂、杀虫剂、杀螨剂、除草剂、植物生长调节剂或肥料等，可产生附加的优点和效果。
应该明确的是，在本发明的权利要求所限定的范围内，可以进行各种变换和改动。
本发明所具有的优点：
本发明以天然产物胡椒酸为先导，通过引入适当的4-七氟异丙基苯胺类活性亚结构得到通式I化合物，由于引入新的结构，提高了分子与受体相互作用和结合的机会，获得了在杀虫、杀螨剂和杀菌活性中意外好的生物活性结果，使得本发明获得的胡椒酸衍生物具有更全面的生物学特性。
具体实施方式
以下具体实施例用来进一步说明本发明，但本发明绝非限于这些例子。
合成实施例
实施例1：化合物I-45的制备
1)N-(2-溴-6-三氟甲基-4-七氟异丙基苯基)-2-氟-3-硝基苯甲酰胺的制备
Figure PCTCN2018092393-appb-000013
向反应瓶中加入2-氟-3-硝基苯甲酸(9.72g，52.4mmol)、氯化亚砜(40.05g)和DMF(0.40g)，升温至80℃反应8小时，减压蒸出氯化亚砜，得到酰氯，加入1,3-二甲基-2-咪唑啉酮(160mL)、2-溴-6-三氟甲基-4-七氟异丙基苯胺(16.40g，40.0mmol)和碘化钾(1.68g)，升温至100℃反应48小时。反应液降至室温，过滤除去不溶物，加入乙酸乙酯(100mL)溶解，依次用饱和碳酸氢钠水溶液和饱和食盐水洗涤，分出有机相，将有机相用无水硫酸镁干燥，过滤后减压蒸出有机溶剂，残余物经柱色谱分离纯化得标题物，白色固体2.10g，收率为9％(以2-溴-6-三氟甲基-4-七氟异丙基苯胺计)。
1H NMR(300MHz,CDCl 3,ppm):8.47-8.42(m,1H),8.32-8.26(m,1H),8.21(d,1H),8.17(s,1H),7.94(s,1H),7.55-7.49(m,1H).
2)N-(2-溴-6-三氟甲基-4-七氟异丙基苯基)-2-氟-3-氨基苯甲酰胺的制备
Figure PCTCN2018092393-appb-000014
向反应瓶中加入N-(2-溴-6-三氟甲基-4-七氟异丙基苯基)-2-氟-3-硝基苯甲酰胺(1.44g，2.5mmol)、二氧六环(10mL)和氯化亚锡(2.28g，10.0mmol))，缓慢滴入浓盐酸(2mL)。升温至60-65℃反应，TLC监测至反应完全。冷却至室温，将反应液倾入冰水(15mL)中，加入乙酸乙酯(30mL)，缓慢加入氢氧化钠中和至pH＝8-9。将析出的沉淀经硅藻土过滤后，用乙酸乙酯洗涤滤饼，将滤液分层。用无水硫酸镁干燥有机相，减压蒸出有机溶剂，残余物经柱色谱分离纯化得标题物，黄色固体1.26g，收率为91％。
1H NMR(300MHz,CDCl 3,ppm):8.29(d,1H),8.13(s,1H),7.91(s,1H),7.50-7.44(m,1H),7.12-7.07(m,1H),7.04-6.94(m,1H),3.93(br.s,2H).
3)N-(2-溴-6-三氟甲基-4-七氟异丙基苯基)-2-氟-3-甲胺基苯甲酰胺的制备
Figure PCTCN2018092393-appb-000015
向反应瓶中加入浓硫酸(3mL)和N-(2-溴-6-三氟甲基-4-七氟异丙基苯基)-2-氟-3-氨基苯甲酰胺(0.55g，1.0mmol)，充分搅拌溶解。保持温度在30-35℃，缓慢滴入甲醛水溶液(2mL)，滴毕，升温至40℃继续反应，TLC监测至反应完全。冷却至室温，将反应液缓慢倾入冰水(10mL)中，充分搅拌，析出固体，过滤，滤饼经柱色谱分离纯化得标题物，白色固体0.52g，收率为92％。
1H NMR(300MHz,CDCl 3,ppm):8.28(d,1H),8.13(s,1H),7.90(s,1H),7.40-7.36(m,1H),7.19-7.14(m,1H),6.93-6.88(m,1H),4.13(br.s,1H),2.94(s,3H).
4)N-(2-溴-6-三氟甲基-4-七氟异丙基苯基)-2-氟-3-(N-甲基-2,2-二氟-1,3-苯并二噁茂-5-甲酰胺基)苯甲酰胺(化合物I-45)的制备
Figure PCTCN2018092393-appb-000016
向反应瓶中加入2,2-二氟-1,3-苯并二噁茂-5-甲酸(0.21g，1.0mmol)、氯化亚砜(1.02g)、甲苯(10mL)和DMF(1滴)，升温至80℃反应4小时，减压蒸出氯化亚砜，得到的酰氯溶于甲苯(20mL)中，加入N-(2-溴-6-三氟甲基-4-七氟异丙基苯基)-2-氟-3-甲胺基苯甲酰胺(0.51g，0.9mmol)升温至110℃反应，TLC监测至反应完全。反应液降至室温，充分搅拌，逐渐析出固体，过滤，滤饼经柱色谱分离纯化得标题物，白色固体0.57g，收率为84％(以N-(2-溴-6-三氟甲基-4-七氟异丙基苯基)-2-氟-3-甲胺基苯甲酰胺计)。
1H NMR(300MHz,CDCl 3,ppm):8.13-8.04(m,3H),7.91(s,1H),7.52-7.47(m,1H),7.37-7.31(m,1H),7.20(s,1H),7.02(d,1H),6.87(d,1H),3.51(s,3H).
实施例2：化合物I-2的制备
Figure PCTCN2018092393-appb-000017
向反应瓶中加入2,2-二氟-1,3-苯并二噁茂-5-甲酸(0.21g，1.0mmol)、氯化亚砜(1.08g)、甲苯(10mL)和DMF(1滴)，升温至80℃反应4小时，减压蒸出氯化亚砜，得到的酰氯溶于甲苯(20mL)中，加入N-(2-溴-6-三氟甲基-4-七氟异丙基苯基)-2-氟-3-氨基苯甲酰胺(0.50g，0.9mmol)升温至110℃反应，TLC监测至反应完全。反应液降至室温，充分搅拌，逐渐析出固体，过滤，滤饼经柱色谱分离纯化得标题物，白色固体0.55g，收率为83％(以N-(2-溴-6-三氟甲基-4-七氟异丙基苯基)-2-氟-3-氨基苯甲酰胺计)。
1H NMR(300MHz,CDCl 3,ppm):8.20(s,1H),7.99(s,1H),7.47(d,1H),7.38(s,1H),6.96-6.80(m,4H),6.71-6.65(m,1H).
实施例3：化合物I-51的制备
1)N-(2,6-二溴-4-七氟异丙基苯基)-2-氟-3-硝基苯甲酰胺的制备
Figure PCTCN2018092393-appb-000018
向反应瓶中加入2-氟-3-硝基苯甲酸(3.71g，20.0mmol)、氯化亚砜(16.05g)和DMF(0.20g)，升温至80℃反应6小时，减压蒸出氯化亚砜，得到酰氯，加入乙腈(40mL)、2,6- 二溴-4-七氟异丙基苯胺(4.23g，10.0mmol)、碘化钾(0.42g)，升温至100℃反应，TLC监测至反应完全，约8小时。反应液降至室温，过滤除去不溶物，减压蒸出乙腈，加入乙酸乙酯(30mL)溶解，依次用饱和碳酸氢钠水溶液和饱和食盐水洗涤，分出有机相，将有机相用无水硫酸镁干燥，过滤后减压蒸出有机溶剂，残余物经柱色谱分离纯化得标题物，白色固体5.42g，收率为91％(以2,6-二溴-4-七氟异丙基苯胺计)。
1H NMR(300MHz,CDCl 3,ppm):8.51-8.46(m,1H),8.31-8.27(m,1H),8.16(d,1H),7.91(s,2H),7.55-7.51(m,1H).
2)N-(2,6-二溴-4-七氟异丙基苯基)-2-氟-3-氨基苯甲酰胺的制备
Figure PCTCN2018092393-appb-000019
向反应瓶中加入N-(2,6-二溴-4-七氟异丙基苯基)-2-氟-3-硝基苯甲酰胺(1.48g，2.5mmol)、二氧六环(10mL)和氯化亚锡(2.28g，10.0mmol))，缓慢滴入浓盐酸(2mL)。升温至60-65℃反应，TLC监测至反应完全。冷却至室温，将反应液倾入冰水(15mL)中，加入乙酸乙酯(30mL)，缓慢加入氢氧化钠中和至pH＝8-9。将析出的沉淀经硅藻土过滤后，用乙酸乙酯洗涤滤饼，将滤液分层。用无水硫酸镁干燥有机相，减压蒸出有机溶剂，残余物经柱色谱分离纯化得标题物，黄色固体1.30g，收率为92％。
1H NMR(300MHz,CDCl 3,ppm):8.28(d,1H),8.13(s,1H),7.90(s,1H),7.49-7.47(m,1H),7.13-7.10(m,1H),7.04-6.99(m,1H),3.94(br.s,1H).
3)N-(2,6-二溴-4-七氟异丙基苯基)-2-氟-3-(甲胺基)苯甲酰胺的制备
Figure PCTCN2018092393-appb-000020
向反应瓶中加入浓硫酸(3mL)和N-(2,6-二溴-4-七氟异丙基苯基)-2-氟-3-氨基苯甲酰胺(0.56g，1.0mmol)，充分搅拌溶解。保持温度在30-35℃，缓慢滴入甲醛水溶液(2mL)，滴毕，升温至40℃继续反应，TLC监测至反应完全。冷却至室温，将反应液缓慢倾入冰水(10mL)中，充分搅拌，析出固体，过滤，滤饼经柱色谱分离纯化得标题物，白色固体0.54g，收率为93％。
1H NMR(300MHz,CDCl 3,ppm):8.20(d,1H),7.87(s,2H),7.43-7.29(m,1H),7.20-7.18(m,1H),6.93-6.88(m,1H),4.91-4.87(m,1H),2.94(d,3H).
4)N-(2,6-二溴-4-七氟异丙基苯基)-2-氟-3-(N-甲基-2,2-二氟-1,3-苯并二噁茂-5-甲酰胺基)苯甲酰胺(化合物I-51)的制备
Figure PCTCN2018092393-appb-000021
向反应瓶中加入2,2-二氟-1,3-苯并二噁茂-5-甲酸(0.21g，1.0mmol)、氯化亚砜(1.01g)、甲苯(10mL)和DMF(1滴)，升温至80℃反应4小时，减压蒸出氯化亚砜，得到的酰氯溶 于甲苯(20mL)中，加入N-(2,6-二溴-4-七氟异丙基苯基)-2-氟-3-甲胺基苯甲酰胺(0.52g，0.9mmol)升温至110℃反应，TLC监测至反应完全。反应液降至室温，充分搅拌，逐渐析出固体，过滤，滤饼经柱色谱分离纯化得标题物，白色固体0.60g，熔点：157-158℃，收率为87％(以N-(2,6-二溴-4-七氟异丙基苯基)-2-氟-3-甲胺基苯甲酰胺计)。
1H NMR(300MHz,CDCl 3,ppm):8.09-8.04(m,2H),7.87(s,2H),7.47-7.43(m,1H),7.34-7.29(m,1H),7.20(s,1H),7.05(d,1H),6.89(d,1H),3.50(s,3H).
实施例4：化合物I-8的制备
Figure PCTCN2018092393-appb-000022
向反应瓶中加入2,2-二氟-1,3-苯并二噁茂-5-甲酸(0.21g，1.0mmol)、氯化亚砜(1.06g)、甲苯(10mL)和DMF(1滴)，升温至80℃反应4小时，减压蒸出氯化亚砜，得到的酰氯溶于甲苯(20mL)中，加入N-(2,6-二溴-4-七氟异丙基苯基)-2-氟-3-氨基苯甲酰胺(0.51g，0.9mmol)升温至110℃反应，TLC监测至反应完全。反应液降至室温，充分搅拌，逐渐析出固体，过滤，滤饼经柱色谱分离纯化得标题物，白色固体0.54g，熔点：176-177℃，收率为80％(以N-(2,6-二溴-4-七氟异丙基苯基)-2-氟-3-氨基苯甲酰胺计)。
1H NMR(300MHz,CDCl 3,ppm):8.57-8.52(m,1H),8.17-8.12(m,2H),7.90-7.86(m,3H),7.70-7.68(m,2H),7.39-7.34(m,1H),7.20(d,1H).
实施例5：化合物I-5的制备
1)2-氟-3-(2,2-二氟-1,3-苯并二噁茂-5-甲酰胺基)苯甲酸甲酯(化合物II-1)的制备
Figure PCTCN2018092393-appb-000023
向反应瓶中加入2,2-二氟-1,3-苯并二噁茂-5-甲酸(4.08g，20mmol)、氯化亚砜(21.40g)和DMF(0.10g)，升温回流6小时，减压蒸出氯化亚砜，得到酰氯，加入甲苯(30mL)和2-氟-3-氨基苯甲酸甲酯(3.42g，20mmol)，升温回流3小时，冷却至室温后，有固体析出，过滤，滤饼经柱色谱分离纯化得标题物，白色固体5.89g，熔点：130-131℃，收率为82％(以2-氟-3-氨基苯甲酸甲酯计)。
1H NMR(300MHz,CDCl 3,ppm):10.15(s,1H),7.93-7.87(m,3H),7.74-7.69(m,1H),7.41(d,1H),7.34-7.28(m,1H),3.89(s,3H).
2)2-氟-3-(2,2-二氟-1,3-苯并二噁茂-5-甲酰胺基)苯甲酸(化合物II-7)的制备
Figure PCTCN2018092393-appb-000024
向反应瓶中加入氢氧化钠(0.62g，15mmol)、水(10mL)和甲醇(10mL)，待氢氧化钠溶解后，加入2-氟-3-(2,2-二氟-1,3-苯并二噁茂-5-甲酰胺基)苯甲酸甲酯(3.57g，10mmol) 升温至60-65℃反应，TLC监测至反应完全。冷却至室温，加入乙酸乙酯(5mL)，萃取分层，水相边搅拌边用1N盐酸调节至pH＝2-3，析出固体，过滤，滤饼干燥得标题物，白色固体3.13g，熔点：266-267℃，收率为91％。
1H NMR(300MHz,CDCl 3,ppm):13.18(br.s,1H),10.21(s,1H),7.95-7.90(m,2H),7.84-7.80(m,1H),7.74-7.69(m,1H),7.51(d,1H),7.31-7.26(m,1H).
3)N-(2-碘-6-溴-4-七氟异丙基苯基)-2-氟-3-(2,2-二氟-1,3-苯并二噁茂-5-甲酰胺基)苯甲酰胺(化合物I-5)的制备
Figure PCTCN2018092393-appb-000025
向反应瓶中加入2-氟-3-(2,2-二氟-1,3-苯并二噁茂-5-甲酰氨基)苯甲酸(2.06g，6.0mmol)、氯化亚砜(3.60g)、甲苯(10mL)和DMF(1滴)，升温至100℃反应4小时，减压蒸出氯化亚砜和甲苯，得到酰氯(化合物II-9)，白色固体(熔点:155-156℃)，加入乙腈(15mL)、2-碘-6-溴-4-七氟异丙基苯胺(1.88g，4.0mmol)和碘化钾(0.17g，1.0mmol)，升温回流反应8小时。冷却至室温，加入乙酸乙酯(30mL)，依次用饱和碳酸氢钠水溶液和饱和食盐水洗涤，用无水硫酸镁干燥，过滤，减压蒸出溶剂，残余物经柱色谱分离纯化得标题物，白色固体2.58g，收率为81％(以2-碘-6-溴-4-七氟异丙基苯胺计)。
化合物II-9: 1H NMR(300MHz,CDCl 3,ppm):8.80-8.75(m,1H),8.05(br.s,1H),7.90-7.85(m,1H),7.66-7.64(m,2H),7.39-7.33(m,1H),7.20(d,1H).
化合物I-5: 1H NMR(300MHz,CDCl 3,ppm):8.62-8.57(m,1H),8.12-8.05(m,3H),7.96-7.91(m,2H),7.70-7.68(m,2H),7.42-7.36(m,1H),7.21(d,1H).
实施例6：化合物I-48的制备
1)2-氟-3-(N-甲基-2,2-二氟-1,3-苯并二噁茂-5-甲酰胺基)苯甲酸甲酯(化合物II-12)的制备
Figure PCTCN2018092393-appb-000026
向反应瓶中加入2,2-二氟-1,3-苯并二噁茂-5-甲酸(4.08g，20mmol)、氯化亚砜(21.40g)和DMF(0.10g)，升温回流6小时，减压蒸出氯化亚砜，得到酰氯，加入甲苯(30mL)和2-氟-3-甲胺基苯甲酸甲酯(3.70g，20mmol)，升温回流3小时，冷却至室温后，有固体析出，过滤，滤饼经柱色谱分离纯化得标题物，白色固体5.90g，收率为79％(以2-氟-3-甲胺基苯甲酸甲酯计)。
1H NMR(300MHz,CDCl 3,ppm):7.86-7.80(m,1H),7.26-7.22(m,1H),7.14-7.09(m,2H),7.03(d,1H),6.85(d,1H),3.94(s,3H),3.42(s,3H).
2)2-氟-3-(N-甲基-2,2-二氟-1,3-苯并二噁茂-5-甲酰胺基)苯甲酸(化合物II-18)的制备
Figure PCTCN2018092393-appb-000027
向反应瓶中加入氢氧化钠(0.62g，15mmol)、水(10mL)和甲醇(10mL)，待氢氧化钠溶解后，加入2-氟-3-(N-甲基-2,2-二氟-1,3-苯并二噁茂-5-甲酰胺基)苯甲酸甲酯(3.71g，10mmol)升温至60-65℃反应，TLC监测至反应完全。冷却至室温，加入乙酸乙酯(5mL)，萃取分层，水相边搅拌边用1N盐酸调节至pH＝2-3，析出固体，过滤，滤饼干燥得标题物，白色固体3.15g，收率为88％。
1H NMR(300MHz,CDCl 3,ppm):13.09(br.s,1H),7.86-7.83(m,1H),7.76-7.71(m,2H),7.59-7.55(m,1H),7.39(d,1H),7.21-7.16(m,1H),3.32(s,3H).
3)N-(2-碘-6-溴-4-七氟异丙基苯基)-2-氟-3-(N-甲基-2,2-二氟-1,3-苯并二噁茂-5-甲酰胺基)苯甲酰胺(化合物I-48)的制备
Figure PCTCN2018092393-appb-000028
向反应瓶中加入2-氟-3-(N-甲基-2,2-二氟-1,3-苯并二噁茂-5-甲酰氨基)苯甲酸(2.14g，6.0mmol)、三溴化磷(0.42g)和甲苯(10mL)，升温至100℃反应4小时，减压蒸出甲苯，得到酰溴(化合物II-21)，黄色油，加入乙腈(15mL)、2-碘-6-溴-4-七氟异丙基苯胺(1.88g，4.0mmol)和碘化钾(0.17g，1.0mmol)，升温回流反应8小时。冷却至室温，加入乙酸乙酯(30mL)，依次用饱和碳酸氢钠水溶液和饱和食盐水洗涤，用无水硫酸镁干燥，过滤，减压蒸出溶剂，残余物经柱色谱分离纯化得标题物，白色固体2.64g，熔点：185-186℃，收率为81％(以2-碘-6-溴-4-七氟异丙基苯胺计)。
化合物I-48: 1H NMR(300MHz,CDCl 3,ppm):8.10-8.03(m,3H),7.89(s,1H),7.49-7.44(m,1H),7.35-7.30(m,1H),7.20(s,1H),7.05(d,1H),6.88(d,1H),3.50(s,3H).
实施例7：化合物I-8的制备
Figure PCTCN2018092393-appb-000029
向反应瓶中加入2-氟-3-(2,2-二氟-1,3-苯并二噁茂-5-甲酰氨基)苯甲酸(2.06g，6.0mmol)、对硝基苯磺酰氯(1.33g，6.0mmol)、乙腈(25mL)和三乙胺(0.67g，6.6mmol)，升温回流反应4小时，加入2,6-二溴-4-七氟异丙基苯胺(1.69g，4.0mmol)和碘化钾(0.17g，1.0mmol)，继续回流反应24小时。冷却至室温，加入乙酸乙酯(30mL)，依次用饱和碳酸氢钠水溶液和饱和食盐水洗涤，用无水硫酸镁干燥，过滤，减压蒸出溶剂，残余物经柱色谱分离纯化得标题物，白色固体1.82g，熔点：176-177℃，收率为60％(以2,6-二溴-4-七氟异丙基苯胺计)。
实施例8：化合物I-44的制备
Figure PCTCN2018092393-appb-000030
向反应瓶中加入2-氟-3-(N-甲基-2,2-二氟-1,3-苯并二噁茂-5-甲酰氨基)苯甲酸(2.14g，6.0mmol)、氯化亚砜(3.60g)、甲苯(10mL)，升温至100℃反应6小时，减压蒸出氯化亚砜和甲苯，得到酰氯(化合物II-20)，黄色油，加入乙腈(15mL)、2,6-二碘-4-七氟异丙基苯胺(2.07g，4.0mmol)和碘化钾(0.17g，1.0mmol)，升温回流反应8小时。冷却至室温，加入乙酸乙酯(30mL)，依次用饱和碳酸氢钠水溶液和饱和食盐水洗涤，用无水硫酸镁干燥，过滤，减压蒸出溶剂，残余物经柱色谱分离纯化得标题物，白色固体2.70g，收率为78％(以2,6-二碘-4-七氟异丙基苯胺计)。
化合物I-44: 1H NMR(300MHz,CDCl 3,ppm):8.08-8.03(m,2H),7.86(s,2H),7.45-7.41(m,1H),7.33-7.28(m,1H),7.20(s,1H),7.05(d,1H),6.90(d,1H),3.50(s,3H).
同时按照上述记载的方式还能够制备获得通式I所示的其它化合物。
生物活性测定
实施例9杀虫活性测定
根据待测化合物的溶解性，用丙酮或二甲基亚砜溶解，然后用0.1％的吐温80溶液配制成所需浓度的待测液50毫升，丙酮或二甲基亚砜在总溶液中的含量不超过10％，待用。
实施例9.1对粘虫活性的测定
选新鲜玉米中部叶片剪成3厘米小段，放入至上述配制好的药液中浸渍10秒，阴干后置于放有滤纸的直径为9厘米的培养皿中，接入整齐的健康试虫(3龄)，每处理14头，试验设4次重复，设清水处理为空白对照。处理后放入24℃、相对湿度60％-70％、自然光照的室内培养，72小时后调查存活虫数，计算死亡率。
部分供试的化合物中，化合物I-2、I-5、I-8、I-44、I-45、I-48和I-51在浓度为0.3mg/L时对粘虫的防效较好，死亡率在90％以上。
按照以上试验方法，选取化合物I-8、I-51和已知化合物KC 1(US2014206727A1中的化合物160)和KC 3(US8853440B2中的化合物3-14)进行杀粘虫活性的平行测定，试验结果见表1。
表1：化合物I-8、I-51、KC 1和KC 3对粘虫活性的平行测定结果(死亡率，％)
Figure PCTCN2018092393-appb-000031
实施例9.2对小菜蛾活性的测定
选室温培养的甘蓝叶片，除去表面蜡质层，用打孔器打成直径为2厘米的圆形叶碟，放入至配制好的药液中浸渍10秒，阴干后置于放有滤纸的直径为9厘米的培养皿中，接入整齐的健康试虫(2龄)，每处理10头，试验设4次重复，设清水处理为空白对照。处理后放入24℃、相 对湿度60％-70％、自然光照的室内培养，72小时后调查存活虫数，计算死亡率。
部分供试的化合物中，化合物I-2、I-5、I-8、I-44、I-45、I-48和I-51在浓度为1mg/L时对小菜蛾的防效较好，死亡率在90％以上。
实施例9.3对甜菜夜蛾活性的测定
将甘蓝叶片用打孔器打成直径1厘米的叶碟，用手持式Airbrush喷雾处理，一定浓度的测试化合物在每叶碟正反面喷雾，喷液量为0.5毫升，阴干后每处理接入12头试虫(3龄)，试验设3次重复，设清水处理为空白对照。处理后放入24℃、相对湿度60％-70％、无光照的室内培养，96小时后调查存活虫数，计算死亡率。化合物I-8和KC 2(US8853440B2中的化合物3-1)对甜菜夜蛾活性的平行测定结果见表2。
表2：化合物I-8和KC 2对甜菜夜蛾活性的平行测定结果(死亡率，％)
Figure PCTCN2018092393-appb-000032
实施例9.4对桃蚜活性的测定
取直径6厘米培养皿，皿底覆一层滤纸，并滴加适量自来水保湿。从培养桃蚜的甘蓝植株上剪取大小适宜(直径约3厘米)且长有15-30头蚜虫的甘蓝叶片，去除有翅蚜和叶片正面的蚜虫，调查结束后，叶背向置于培养皿内，用手持式Airbrush喷雾器进行喷雾处理，压力为10psi(约0.7kg/cm 2),喷液量为0.5毫升，试验设3次重复，处理后置于标准观察室内，48小时后调查存活数，计算死亡率。
部分供试的化合物中，化合物I-8和I-51在浓度为10mg/L时对桃蚜的防效较好，死亡率在80％以上。
实施例9.5对稻纵卷叶螟的田间小区活性测定
一定浓度的测试化合物在稻纵卷叶螟孵化高峰期进行页面喷雾处理，喷液量为每公顷450升。水稻小区面积为32平方米，3次重复。15天后调查存活虫数，计算死亡率。化合物I-8和KC 2对稻纵卷叶螟活性的平行测定结果见表3。
表3：化合物I-8和KC 2对稻纵卷叶螟活性的平行测定结果(死亡率，％)
Figure PCTCN2018092393-appb-000033
实施例10杀螨活性测定
根据待测化合物的溶解性，用丙酮或二甲基亚砜溶解，然后用0.1％的吐温80溶液配制成所需浓度的待测液50毫升，丙酮或二甲基亚砜在总溶液中的含量不超过10％。
取两片真叶菜豆苗，接种朱砂叶螨成螨并调查基数后，用手持式Airbrush喷雾器进行整株喷雾处理，试验设3次重复，处理后置于标准观察室，72小时后调查存活螨数，计算死亡率。对照化合物C 1和C 2(结构式如下)为专利AU2004315003B2公开范围所包含的非列表化合物。化合物I-8、KC 1、KC 2、KC 3、C 1和C 2对朱砂叶螨成螨活性的平行测定结果见表5。
Figure PCTCN2018092393-appb-000034
表4：化合物I-8、KC 1、KC 2、KC 3、C 1和C 2对朱砂叶螨成螨活性的平行测定结果(死亡率，％)
Figure PCTCN2018092393-appb-000035
实施例11杀家蝇幼虫活性测定
采用饲料混毒法对3龄家蝇幼虫测试，按照试验设计剂量用一定浓度的奶粉溶液将1000mg/L的待测化合物的丙酮储液稀释成所需浓度药液，再用移液枪将混毒奶粉溶液均匀加入直径为6cm并放有滤纸的培养皿中，每皿1ml，将3龄家蝇幼虫接入培养皿内，试验设3次重复，处理后置于标准观察室，72h后调查存活虫数，计算死亡率。化合物I-51和KC 2对家蝇幼虫活性的平行测定结果见表6。
表5：化合物I-51和KC 2对家蝇幼虫活性的平行测定结果(死亡率，％)
Figure PCTCN2018092393-appb-000036
实施例12杀菌活性测定
根据待测化合物的溶解性，用丙酮、甲醇或DMF溶解，然后用0.1％的吐温80溶液配制成所需浓度的待测液50毫升，丙酮或二甲基亚砜在总溶液中的含量不超过5％。
选生长整齐一致的两叶期黄瓜幼苗，用一定浓度测试化合物喷雾处理，处理后24小时后接种黄瓜霜霉病孢子悬浮液，然后放入人工气候室培养，待病害侵染后，移入温室正常培养，5天后根据空白对照的发病情况，采用目测法调查防治效果。用100％-0记录防效，100％表示不发病，0表示处理的发病程度同空白对照相当。
部分供试的化合物中，化合物I-8和I-51在浓度为400mg/L时对黄瓜霜霉病的防效达90％以上。
通过本发明上述记载的制备过程获得的通式I所示的其它化合物也具有上述相应的特性，达到意想不到的效果。

Claims (10)

  1. 一种胡椒酸衍生物，其特征在于：胡椒酸衍生物结构如通式I所示：
    Figure PCTCN2018092393-appb-100001
    式中：
    X 1选自卤素；
    X 2选自H或卤素；
    R选自H、C 1-C 3烷基或卤代C 1-C 3烷基；
    Y 1选自卤素或卤代C 1-C 3烷基；
    Y 2选自卤素或卤代C 1-C 3烷基。
  2. 按权利要求1所述的胡椒酸衍生物，其特征在于：所述通式I中：
    X 1选自F、Cl或Br；
    X 2选自H、F、Cl或Br；
    R选自H、甲基或卤代甲基；
    Y 1选自F、Cl、Br、I或卤代甲基；
    Y 2选自F、Cl、Br、I或卤代甲基。
  3. 按权利要求2所述的胡椒酸衍生物，其特征在于：所述通式I中：
    X 1选自F；
    X 2选自H或F。
  4. 按权利要求3所述的胡椒酸衍生物，其特征在于：所述通式I中：
    X 2选自F；
    R选自H或甲基。
  5. 一种化合物，其特征在于：化合物如通式II所示：
    Figure PCTCN2018092393-appb-100002
    X 1选自卤素；
    X 2选自H或卤素；
    R选自H、C 1-C 3烷基或卤代C 1-C 3烷基；
    LG选自C 1-C 6烷氧基、OH或卤素。
  6. 按权利要求5所述的化合物，其特征在于：式中：
    X 1选自F、Cl或Br；
    X 2选自H、F、Cl或Br；
    R选自H、甲基或卤代甲基。
  7. 一种权利要求1所述的胡椒酸衍生物的制备方法，其特征在于：通式II化合物与通式V化合物反应制备通式I化合物，反应式为：
    Figure PCTCN2018092393-appb-100003
    通式II中LG选自C 1-C 6烷氧基、OH或卤素；
    当LG选自C 1-C 6烷氧基时，通式II为通式II-a；当LG选自OH时，通式II为通式II-b；当LG选自卤素时，通式II为通式II-c；
    具体制备方法为：通式II-a化合物水解得通式II-b化合物，通式II-b化合物与适宜的酰卤化试剂反应制得通式II-c化合物，再与通式V化合物反应制得通式I化合物；
    或，通式II-a化合物与通式V化合物直接胺解反应制得通式I化合物；
    或，通式II-b化合物与通式V化合物直接缩合反应制得通式I化合物。
  8. 一种按照权利要求1-4任意一项所述的胡椒酸衍生物在农业、林业或卫生领域用作杀虫剂、杀螨剂或杀菌剂的用途。
  9. 一种杀虫、杀螨或杀菌组合物，含有权利要求1-4任意一项所述的胡椒酸衍生物为活性组分和农业、林业或卫生上可接受的载体，组合物中活性组分的重量百分含量为1-99％。
  10. 一种控制害虫、害螨或有害病菌的方法，其特征在于：将权利要求9所述的组合物以每公顷10克到1000克的有效剂量施于需要控制的害虫、害螨或有害病菌上，或其生长的介质上。
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BR112019027444A2 (pt) 2020-07-07
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EP3647305A1 (en) 2020-05-06
ES2909305T3 (es) 2022-05-06
US20200181107A1 (en) 2020-06-11
BR112019027444B1 (pt) 2023-05-02
US11891371B2 (en) 2024-02-06
CN109206397B (zh) 2022-06-07
EP3647305B1 (en) 2022-02-23

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