WO2017004734A1 - 苄基腙类化合物及其制备方法与应用 - Google Patents

苄基腙类化合物及其制备方法与应用 Download PDF

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WO2017004734A1
WO2017004734A1 PCT/CN2015/000489 CN2015000489W WO2017004734A1 WO 2017004734 A1 WO2017004734 A1 WO 2017004734A1 CN 2015000489 W CN2015000489 W CN 2015000489W WO 2017004734 A1 WO2017004734 A1 WO 2017004734A1
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formula
group
compound
nmr
alkyl
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PCT/CN2015/000489
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French (fr)
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覃兆海
贾长青
肖玉梅
袁小勇
马永强
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中国农业大学
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    • 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
    • A01N35/00—Biocides, pest repellants or attractants, or plant growth regulators containing organic compounds containing a carbon atom having two bonds to hetero atoms with at the most one bond to halogen, e.g. aldehyde radical
    • A01N35/08—Biocides, pest repellants or attractants, or plant growth regulators containing organic compounds containing a carbon atom having two bonds to hetero atoms with at the most one bond to halogen, e.g. aldehyde radical at least one of the bonds to hetero atoms is to nitrogen
    • A01N35/10—Biocides, pest repellants or attractants, or plant growth regulators containing organic compounds containing a carbon atom having two bonds to hetero atoms with at the most one bond to halogen, e.g. aldehyde radical at least one of the bonds to hetero atoms is to nitrogen containing a carbon-to-nitrogen double bond
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C251/00—Compounds containing nitrogen atoms doubly-bound to a carbon skeleton
    • C07C251/72—Hydrazones
    • C07C251/74—Hydrazones having doubly-bound carbon atoms of hydrazone groups bound to hydrogen atoms or to acyclic carbon atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C251/00—Compounds containing nitrogen atoms doubly-bound to a carbon skeleton
    • C07C251/72—Hydrazones
    • C07C251/74—Hydrazones having doubly-bound carbon atoms of hydrazone groups bound to hydrogen atoms or to acyclic carbon atoms
    • C07C251/76—Hydrazones having doubly-bound carbon atoms of hydrazone groups bound to hydrogen atoms or to acyclic carbon atoms to carbon atoms of a saturated carbon skeleton
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C251/00—Compounds containing nitrogen atoms doubly-bound to a carbon skeleton
    • C07C251/72—Hydrazones
    • C07C251/86—Hydrazones having doubly-bound carbon atoms of hydrazone groups bound to carbon atoms of six-membered aromatic rings

Definitions

  • the invention belongs to the field of preparation and application of agricultural fungicides and insecticides, and particularly relates to a benzyl hydrazine compound and a preparation method and application thereof.
  • the methoxy acrylate fungicide is a kind of excellent agricultural fungicide derived from the bactericidal natural antibiotic Strobilurin A. This kind of bactericide is broad-spectrum, high-efficiency, and shows good for almost all fungal diseases. Activity has played an important role in protecting agricultural production.
  • X is selected from CH or N; Y is selected from any one of O, S and NH; R 1 is selected from C 1 - C 8 alkyl, allyl, propargyl, benzyl a benzoyl group, a C 1 -C 5 fatty acyl group, a C 1 -C 5 alkoxycarbonyl group, a cyano group, a carbamoyl group and a thiocarbamoyl group; R 2 is selected from C 1 -C 12 Any one of alkyl, Q 1 and Q 2 ; R 3 is selected from hydrogen, C 1 -C 5 alkyl, Q 1 and Q 2 ;
  • the binding site of R 4 is at least one of the remaining 5 binding sites, wherein, when m>1, R 4 may be the same or different; and the binding site of R 5 is at least of the remaining 4 binding sites.
  • R 5 may be the same or different, wherein, in Q 2 , N may be located at any of the 2, 3, and 4 positions.
  • the benzyl hydrazine compound provided by the present invention has a structural formula of the formula I, preferably a structure: in the formula I, X is selected from CH or N; Y is selected from O or NH; and R 1 is selected from C Any one of a straight or branched alkoxycarbonyl group, a benzoyl group, a cyano group, a carbamoyl group and a thiocarbamoyl group of 1 to C 4 ; R 2 is selected from Q 1 or Q 2 ; and R 3 is selected from the group consisting of Q 1 or Q 2 ; Hydrogen or a C 1 -C 2 alkyl group;
  • the benzyl hydrazine compound provided by the present invention has a structural formula of the formula I, and is further preferably a structure in which X is selected from CH or N; Y is selected from O or NH; and R 1 is selected from the group consisting of a linear or branched alkoxycarbonyl group of C 1 to C 4 , a cyano group; R 2 is selected from Q 1 or Q 2 ; and R 3 is selected from hydrogen or methyl;
  • Halogen refers to fluorine, chlorine, bromine, and iodine.
  • Alkyl a linear or branched alkyl group such as methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, tert-butyl, tert-amyl.
  • the aryl moiety in the aryl group and the aryloxy group includes a phenyl group, a pyridyl group, a furyl group and the like.
  • geometric isomers are formed by attachment of different substituents by carbon-carbon double bonds or carbon-nitrogen double bonds (different configurations are represented by Z and E, respectively).
  • the compound of formula I may be a Z isomer, an E isomer, or a mixture of the two in any ratio.
  • the compounds of the formula I according to the invention may in particular be selected from the following numbered compounds:
  • N in the pyridine ring attached to (R 5 ) n in the above table may be located at the 2, 3 or 4 position.
  • the method for preparing a benzyl hydrazine compound (the compound of the formula I) provided by the invention comprises the steps of: condensing a compound represented by the formula IV and a compound of the formula V in an organic solvent in the presence of a catalyst; The compound of formula I is obtained.
  • R 1 , R 1 and R 3 are the same as defined in the formula I; in the formula V, X and Y are the same as defined in the formula I.
  • the catalyst is a base selected from at least one of sodium hydride, sodium amide, lithium amide, lithium diisopropylamide, n-butyllithium and phenyllithium.
  • the molar ratio of the catalyst to the compound of formula IV is 1: (1.2 to 3).
  • the reaction temperature of the condensation reaction is -5 to 100 ° C, preferably 10 to 50 ° C, specifically 25 ° C, and the reaction time is 2 to 12 h, specifically 4 to 9 h.
  • the molar ratio of the compound of the formula IV to the compound of the formula V is 1: (1-2), specifically 1: (1-1.3).
  • the organic solvent is at least one selected from the group consisting of N,N-dimethylformamide (DMF), N-methylpyrrolidone, and ethylene glycol dimethyl ether.
  • the condensation reaction is preferably carried out as follows: the catalyst and the compound of the formula IV are stirred in an organic solvent at -10 to 5 ° C for 0.5 to 2 h, and the compound of the formula V is added thereto at -5 to 100. The reaction is carried out at ° C for 2-12 h to give the compound of formula I.
  • the compound of the formula IV is prepared by reacting a compound of the formula II and a compound of the formula III in an organic solvent to obtain a compound of the formula IV.
  • R 1 is as defined in the formula I; in the formula III, R 2 and R 3 are the same as defined in the formula I.
  • the reaction temperature of the reaction is -20 to 50 ° C, and the reaction time is 1-6 h.
  • the organic solvent is methanol or ethanol.
  • the compounds of the formula II, the formula III and the formula V are all commercially available, for example, the compound of the formula II may specifically be an alkyl hydrazine, an aryl hydrazine, an acyl hydrazine, an alkoxycarbonyl hydrazine or a semicarbazide.
  • the compound of the formula II may specifically be an alkyl hydrazine, an aryl hydrazine, an acyl hydrazine, an alkoxycarbonyl hydrazine or a semicarbazide.
  • the method for preparing a bactericidal and/or insecticidal composition comprises the steps of: preparing a benzyl sulfonium compound (a compound of the formula I) and an agriculturally acceptable carrier.
  • the benzyl quinone compound may be either a single compound of the invention or a mixture of several compounds of the invention.
  • the agriculturally acceptable carrier has the following characteristics: 1) it is convenient to be applied to the site to be treated after preparation with the active ingredient, for example: plants, seeds or soil; 2) is advantageous for storage, transportation or handling; 3) can be It is a solid or liquid, including substances that are usually gaseous but have been compressed into a liquid.
  • carriers commonly used in the formulation of insecticidal and bactericidal compositions for use in the preparation of agriculture can be used.
  • the agriculturally acceptable carrier may in particular be selected from solid carriers and/or liquid carriers.
  • the solid support is selected from at least one of natural or synthetic silicate, ammonium sulfate, calcium sulfate, aluminum silicate, natural or synthetic resins, polychlorophenol, starch, bentonite, and wax, wherein
  • the natural or synthetic silicate may be specifically selected from at least one of attapulgite, talc, aluminum silicate, diatomaceous earth, mica, montmorillonite and calcium silicate
  • the natural or synthetic resin may be specifically selected from the group consisting of At least one of a benzofuran resin, a styrene polymer (having a molecular weight of 50,000-200,000), and a styrene copolymer (such as a styrene-butadiene copolymer);
  • the wax may be specifically selected from the group consisting of beeswax and/or Or paraffin.
  • the liquid carrier is at least one selected from the group consisting of water, a C 1 -C 4 alcohol, a C 3 -C 8 ketone, an aromatic hydrocarbon, a petroleum fraction, and a C 6 -C 12 chlorinated hydrocarbon, wherein the alcohol is specifically It may be ethanol and/or ethylene glycol, and the ketone may specifically be at least one of acetophenone, acetone, methyl ethyl ketone and cyclohexanone, and the aromatic hydrocarbon may specifically be at least one of benzene, toluene and xylene.
  • the petroleum fraction may specifically be kerosene and/or mineral oil, and the chlorinated hydrocarbon may specifically be at least one of carbon tetrachloride, dichloromethane and trichloroethane.
  • Typical bactericide and/or insecticide compositions are typically processed into the form of a concentrate which is used for transport and which is diluted by the user prior to administration.
  • the bactericide and/or insecticide composition provided by the present invention may further comprise a surfactant.
  • the surfactant may be added in an amount acceptable for the agricultural fungicide and/or the insecticide.
  • the surfactant is selected from at least one of an emulsifier, a dispersant, a wetting agent, and a penetrating agent.
  • the emulsifier may be specifically selected from the group consisting of agricultural milk 500# (calcium alkyl benzoate), agricultural milk 600# phosphate (phenyl phenol polyoxyethyl ether), agricultural milk 700# (alkylphenol formaldehyde resin polyoxygen) At least one of ethyl ether), agricultural milk 1600# (phenethyl phenol polyoxyethyl polypropylene ether), polyoxyalkylene alkyl aryl ether, and ethylene oxide-propylene oxide block copolymerkind.
  • agricultural milk 500# calcium alkyl benzoate
  • agricultural milk 600# phosphate phenyl phenol polyoxyethyl ether
  • agricultural milk 700# alkylphenol formaldehyde resin polyoxygen
  • At least one of ethyl ether agricultural milk 1600# (phenethyl phenol polyoxyethyl polypropylene ether), polyoxyalkylene alkyl aryl ether, and ethylene oxide-propylene
  • the dispersing agent may be specifically selected from the group consisting of polycarboxylates, lignosulfonates, alkylphenol polyoxyethylene formaldehyde condensate sulfates, calcium alkylbenzenesulfonates, sodium benzenesulfonate condensate sodium salts, and lauric sulfate Sodium, at least one of a sulfonated castor oil sodium salt, a sodium alkyl aryl sulfonate, an alkylphenol polyoxyethylene pyrimidine, a fatty acid polyoxyethylene ester, and an ester polyoxyethylene pyrimidine.
  • the wetting agent may specifically be selected from at least one of sodium lauryl sulfate, sodium dodecylbenzenesulfonate, pull-up powder BX, saponin powder, silkworm, and sapindus powder.
  • the penetrant may be specifically selected from at least one of a siloxane polyoxyethylene ether, an alkyl aryl sulfonate, an alcohol ether succinate, and a phenol ether succinate.
  • auxiliaries may be appropriately added to the bactericide and/or insecticide composition of the present invention.
  • the amount of the other auxiliary agent added may be an acceptable amount in the agricultural fungicide and/or the insecticide.
  • the other auxiliary agent may be selected from at least one of a disintegrant, an antifoaming agent, an antifreezing agent, and a thickener.
  • the disintegrant is selected from at least one of bentonite, urea, ammonium sulfate, aluminum chloride, and glucose.
  • the antifoaming agent is selected from at least one of a silicone oil, a silicone compound, a C10-C20 saturated fatty acid compound, and a C8-C10 fatty alcohol compound.
  • the antifreeze agent is selected from at least one of ethylene glycol, propylene glycol, glycerin, and polyethylene glycol.
  • the thickener is selected from at least one of xanthan gum, polyvinyl alcohol, and polyethylene glycol.
  • the corresponding components can be added according to a method known to those skilled in the art, thereby preparing a wettable powder, a powder, a granule, a concentrated emulsion, and an emulsifiable concentrate.
  • dosage forms such as suspending agents, aerosols or aerosols.
  • an effective amount of the bactericidal and/or insecticidal composition of the present invention can be applied according to different crops and diseases, and can be carried out by foliar spray, seed treatment or soil treatment.
  • one or more other bactericides may be added to the bactericide and/or insecticide compositions of the present invention to provide additional advantages and effects; the compounds of Formula I may also be Mixtures of fungicides and/or insecticides.
  • the compound of the formula I of the present invention has broad-spectrum and excellent bactericidal activity and can be used for controlling diseases caused by four common pathogenic fungi: ascomycetes, basidiomycetes, deuteromycetes and oomycetes diseases on various crops. . Good control results can be obtained at very low doses.
  • the compound of the formula I has a certain systemic property and can be used as a foliar and soil fungicide to control diseases on various crops.
  • pepper blight tomato early blight, tomato late blight, rice blast, wheat leaf spot, apple ring disease, rice sheath blight, rice blast, rice blast, rice seedling disease, Wheat powdery mildew, rapeseed sclerotinia, cucumber downy mildew, cucumber blight, cucumber gray mold, cucumber powdery mildew or apple powdery mildew.
  • the compound of the formula I of the present invention also has good insecticidal and acaricidal activity, such as: Ia-84, Id-397, Ih-259, etc., and can be used for controlling pests and mites on various crops.
  • the side chain of the benzyl quinone compound prepared by the invention is a benzyl hydrazine structure, and the benzyl quinone compound and the composition containing the same can control the plant at a small dose (eg: crop: pepper, tomato, rice, wheat) , apples, rapeseed and cucumbers, etc.) harmful fungi and pests (such as: armyworm, diamondback moth, peach aphid and cinnabar), with broad-spectrum and excellent bactericidal and insecticidal effects.
  • a small dose eg: crop: pepper, tomato, rice, wheat
  • apples, rapeseed and cucumbers e., etc.
  • harmful fungi and pests such as: armyworm, diamondback moth, peach aphid and cinnabar
  • Figure 1 is a flow diagram showing the preparation of the compound of formula I.
  • compound Ic-228 white powder, melting point 126-128 ° C, yield 70%, 1 H NMR and 13 C NMR are as follows:
  • composition of the composition comprising the compound of the formula I is as follows: (The following components are all in weight percent, and the active component is metered in after one hundred percent)
  • Composition of wettable powder 50% of compound of formula I, 5% of dispersant polycarboxylate, 3% of wetting agent sodium lauryl sulfate, solid carrier or disintegrant bentonite 42%; The mixture is mixed to obtain a mixture, which is subjected to jet milling to obtain a 50% wettable powder.
  • composition of the emulsifiable concentrate 30% of the compound of the formula I, 12% of the emulsifier polyoxyalkylene alkyl aryl ether, 10% of the alkyl aryl sulfonate sulfonate, 48% of the liquid carrier cyclohexanone; The ratios were mixed to give a clear solution of 30% of the compound.
  • composition of water-dispersible granules 70% of the compound of formula I, dispersant alkyl benzene sulfonate 3%, dispersant lignin sulfonate 3%, wetting agent sodium lauryl sulfate 4%, solid carrier or filler starch 20%; the components are mixed in the above ratio to obtain 70% of the compound of formula I Water dispersible granules.
  • the test method is as follows: using a live pot assay method: the original drug of the compound of formula I to be tested (ie, the pure compound of formula I) is used in a small amount of N, N-di Methylformamide was dissolved, diluted with water to the required scale, involving the experimental group and the control group: the experimental group was spray applied to the plant test material, and the disease was inoculated 24 hours later; the control group was not sprayed onto the plant test material.
  • Control effect (1 - disease index after treatment / blank control disease index) ⁇ 100%
  • Compounds Ia-87, Ic-124, and Ih-261 were applied to tomato early blight, rice blast, wheat leaf spot, apple ring disease, rice sheath blight, rice blast, rice when spray application rate was 50 ppm.
  • the control effects of rice false smut, rice seedling disease, rapeseed sclerotium, cucumber downy mildew, cucumber gray mold and cucumber powdery mildew all exceeded 80%.
  • Example 11 Determination of insecticidal and acaricidal activity:
  • Insecticides and mites are tested for insecticidal activity by measuring the compound of formula I with a small amount of N,N-dimethylformamide and diluting with water to the desired scale;
  • the armyworm, the diamondback moth, the peach aphid and the cinnabar leafhopper were used as test materials, and the insecticidal activity was measured by the airbrush spray method.
  • the airbrush spray treatment pressure was 10 psi, and the spray volume was 0.5 ml. After 2-3 days after treatment, the mortality of the tested materials was investigated.
  • the mortality rates of the compound Ic-315, Ih246, and Id-374 against the armyworm, the diamondback moth, the peach aphid, and the cinnabar were more than 60%.
  • the compound of the formula I provided by the invention has broad-spectrum and excellent bactericidal activity and can be used for controlling the diseases caused by four common pathogenic fungi: ascomycetes, basidiomycetes, deuteromycetes and oomycetes on various crops. Disease. Good control results can be obtained at low doses and are widely used in plant fungicides and/or insecticides.

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Abstract

本发明公开了一种式I所示化合物及其制备方法与应用。所述式I中，各取代基的定义见说明书。制备方法包括如下步骤：在催化剂存在下，将式IV所示化合物和式V所示化合物于有机溶剂中进行缩合反应，得到式I所示化合物，该制备方法简单，所得式I所示化合物可用于防治在多种植物上由卵菌、担子菌、子囊菌和半知菌类等多种病菌引起的病害，对小麦白粉病、玉米锈病、西瓜炭疽病等效果尤佳，在低浓度下即可取得很好的防治效果。同时式I所示化合物中的部分化合物还有很好的杀虫和杀螨活性，可用于防治多种作物上的害虫和螨。故在农业和其它领域中可用作杀菌剂或杀虫剂。

Description

苄基腙类化合物及其制备方法与应用 技术领域
本发明属于农用杀菌剂和杀虫剂的制备及应用领域，具体涉及一种苄基腙类化合物及其制备方法与应用。
背景技术
甲氧基丙烯酸酯类杀菌剂是源于具有杀菌活性的天然抗生素Strobilurin A的一类效果卓越的农用杀菌剂，该类杀菌剂广谱、高效，对几乎所有真菌类病害都显示出很好的活性，对农业生产起到了重要的保护作用。
关于甲氧基丙烯酸酯类化合物的结构改造非常多，这些改造多在侧链上的变化，但结构仅有二芳醚类、苄醚类和苄肟醚类三种，结构类型和应用范围有限，同时，此类化合物作为杀菌剂也逐渐产生严重的抗性问题。
发明公开
本发明的目的在于提供一种苄基腙类化合物及其制备方法。
本发明所提供的苄基腙类化合物的结构通式如式I所示：
Figure PCTCN2015000489-appb-000001
所述式I中，X选自CH或N；Y选自O、S和NH中的任一种；R1选自C1-C8的烷基、烯丙基、炔丙基、苄基、苯甲酰基、C1-C5脂肪酰基、C1-C5的烷氧羰基、氰基、氨基甲酰基和硫代氨基甲酰基中的任一种；R2选自C1-C12烷基、Q1和Q2中的任一种；R3选自氢、C1-C5的烷基、Q1和Q2中的任一种；
Figure PCTCN2015000489-appb-000002
其中，所述Q1和Q2中，R4和R5均选自氢、C1-C5的烷基、C1-C5的烷氧基、C1-C5的氟代烷基、C1-C5的氟代烷氧基、卤素、硝基、氰基、苯氧基、吡啶氧基、甲磺酰基和三氟甲磺酰基中的至少一种，所述卤素选自氟、氯、溴和碘中的任一种；m＝0-5；n＝0-4。
R4的结合位点为剩余的5个结合位点中的至少一个，其中，当m>1时，R4可相同或不同；R5的结合位点为剩余4个结合位点中的至少一个，其中，当n>1时，R5可相同或不同，其中，Q2中，N可位于2、3和4位中的任一处。
本发明所提供的苄基腙类化合物的结构通式如式I所示，优选为如下结构：所述式I中，X选自CH或N；Y选自O或NH；R1选自C1～C4的直链或支链烷氧羰基、苯甲酰基、氰基、氨基甲酰基和硫代氨基甲酰基中的任一种；R2选自Q1或Q2；R3选自氢或C1-C2的烷基；
其中，所述Q1和Q2中，R4和R5均选自C1-C5的烷基、三氟甲基、三氟甲氧基、苯氧基、卤素、硝基、氰基、吡啶氧基、甲磺酰基和三氟甲磺酰基中的至少一种；m＝0-3；n＝0-2。
本发明所提供的苄基腙类化合物的结构通式如式I所示，进一步优选为如下结构：所述式I中，X选自CH或N；Y选自O或NH；R1选自C1～C4的直链或支链烷氧羰基、氰基；R2选自Q1或Q2；R3选自氢或甲基；
其中，所述Q1和Q2中，R4和R5均选自三氟甲基、三氟甲氧基、苯氧基、氟、氯、硝基、氰基、吡啶氧基、甲磺酰基和三氟甲磺酰基中的至少一种；m＝0-3，n＝0-2。
本发明的所述的式I化合物的定义中所涉及到的术语代表如下取代基：
卤素：指氟、氯、溴、碘。
烷基：直链或支链烷基，例如：甲基、乙基、正丙基、异丙基、正丁基、异丁基、叔丁基、叔戊基。
芳基以及芳氧基中的芳基部分包括苯基、吡啶基、呋喃基等。
此外，本发明所述的式I化合物中，因碳-碳双键或碳-氮双键连接不同取代基而形成几何异构体(分别以Z和E来表示不同的构型)。本发明所 述的式I化合物可为Z型异构体，亦可为E型异构体，或者两者任何比例的混合物。
本发明的所述的式I化合物具体可选自如下编号的化合物：
Figure PCTCN2015000489-appb-000003
Figure PCTCN2015000489-appb-000004
Figure PCTCN2015000489-appb-000005
Figure PCTCN2015000489-appb-000006
Figure PCTCN2015000489-appb-000007
Figure PCTCN2015000489-appb-000008
Figure PCTCN2015000489-appb-000009
Figure PCTCN2015000489-appb-000010
Figure PCTCN2015000489-appb-000011
Figure PCTCN2015000489-appb-000012
Figure PCTCN2015000489-appb-000013
Figure PCTCN2015000489-appb-000014
Figure PCTCN2015000489-appb-000015
Figure PCTCN2015000489-appb-000016
Figure PCTCN2015000489-appb-000017
Figure PCTCN2015000489-appb-000018
Figure PCTCN2015000489-appb-000019
Figure PCTCN2015000489-appb-000020
Figure PCTCN2015000489-appb-000021
Figure PCTCN2015000489-appb-000022
Figure PCTCN2015000489-appb-000023
Figure PCTCN2015000489-appb-000024
Figure PCTCN2015000489-appb-000025
Figure PCTCN2015000489-appb-000026
Figure PCTCN2015000489-appb-000027
Figure PCTCN2015000489-appb-000028
Figure PCTCN2015000489-appb-000029
Figure PCTCN2015000489-appb-000030
Figure PCTCN2015000489-appb-000031
注：上表中与(R5)n相连的吡啶环中的N可位于2、3或4位。
本发明所提供的苄基腙类化合物(式I所示化合物)的制备方法，包括如下步骤：在催化剂存在下，将式IV所示化合物和式V所示化合物于有机溶剂中进行缩合反应，得到式I所示化合物。
Figure PCTCN2015000489-appb-000032
所述式IV中，R1、R1和R3的定义均同式I；所述式V中，X和Y的定义均同式I。
上述制备方法中，所述催化剂为碱，所述碱选自氢化钠、氨基钠、氨基锂、二异丙基氨基锂、正丁基锂和苯基锂中的至少一种。
所述催化剂和式IV所示化合物的摩尔比为1:(1.2～3)。
所述缩合反应的反应温度为-5～100℃，优选为10～50℃，具体可为25℃，反应时间为2-12h，具体可为4-9h。
所述式IV所示化合物和式V所示化合物的摩尔比为1：(1-2)，具体可为1：(1-1.3)。
所述有机溶剂选自N,N-二甲基甲酰胺(DMF)、N-甲基吡咯烷酮和乙二醇二甲醚中的至少一种。
所述缩合反应优选为按如下步骤进行：将催化剂和式IV所示化合物在有机溶剂中，于-10-5℃下搅拌0.5-2h，再向其中加入式V所示化合物于-5～100℃下反应2-12h，得到式I所示化合物。
上述制备方法中，式IV所示化合物按如下方法制备得到：将式II所示化合物和式III所示化合物于有机溶剂中进行反应，得到式IV所示化合物，
Figure PCTCN2015000489-appb-000033
所述式II中，R1的定义同式I；所述式III中，R2和R3的定义均同式I。
其中，II所示化合物和式III所示化合物的摩尔比为1：(1-2)，具体可为1:1。
所述反应的反应温度为-20～50℃，反应时间为1-6h。
所述有机溶剂为甲醇或乙醇。
所述式II、式III和式V所示化合物均可通过商业途径购得，如：式II所示化合物具体可为烷基肼、芳基肼、酰基肼、烷氧羰基肼、氨基脲、氨基硫脲或氰基肼等
本发明的再一个目的是提供一种杀菌剂和/或杀虫剂组合物及其制备方法，该组合物包括苄基腙类化合物(式I所示化合物)和农业上可接受的载体，其中，该组合物中苄基腙类化合物(活性成分)的重量百分含量为0.1～99％，具体可为30～60％。
本发明所提供的杀菌剂和/或杀虫剂组合物的制备方法，包括如下步骤：将苄基腙类化合物(式I所示化合物)和农业上可接受的载体混合即可制备得到。
所述苄基腙类化合物既可为本发明的单一化合物，也可为本发明几种化合物的混合物。
所述农业上可接受的载体具有如下特点：1)与活性成分配制后便于施用于待处理的位点，例如：植物、种子或土壤；2)有利于贮存、运输或操作；3)可为是固体或液体，包括通常为气体但已压缩成液体的物质。总之，在配制农业上所用杀虫、杀菌组合物中常用的载体均可使用。
所述农业上可接受的载体具体可选自固体载体和/或液体载体。
所述固体载体选自天然或合成的硅酸盐、硫酸铵、硫酸钙、氧化硅酸铝、天然或合成的树脂、多氯苯酚、淀粉、膨润土和蜡中的至少一种，其中，所述天然或合成的硅酸盐具体可选自硅镁土、滑石、硅酸铝、硅藻土、云母、蒙脱石和硅酸钙中的至少一种，所述天然或合成的树脂具体可选自苯并呋喃树脂、苯乙烯聚合物(分子量为5-20万)和苯乙烯共聚物(如：苯乙烯-丁二烯共聚物)中的至少一种；所述蜡具体可选自蜂蜡和/或石蜡。
所述液体载体选自水、C1-C4的醇、C3-C8的酮、芳烃、石油馏分和C6-C12的氯代烃中的至少一种，其中，所述醇具体可为乙醇和/或乙二醇， 所述酮具体可为苯乙酮、丙酮、甲乙酮和环己酮中的至少一种，所述芳烃具体可为苯、甲苯和二甲苯中的至少一种，所述石油馏分具体可为煤油和/或矿物油，所述氯代烃具体可为四氯化碳、二氯甲烷和三氯乙烷中的至少一种。
一般杀菌剂和/或杀虫剂组合物通常会被加工成浓缩物的形式，并以此用于运输，在施用之前由使用者将其稀释。
为了利于稀释，本发明所提供的杀菌剂和/或杀虫剂组合物，还可包括表面活性剂。
所述表面活性剂的添加量为农业上用杀菌剂和/或杀虫剂中可接受的量即可。
所述表面活性剂选自乳化剂、分散剂、润湿剂和渗透剂中的至少一种。
所述乳化剂具体可选自农乳500#(烷基苯黄酸钙)，农乳600#磷酸酯(苯基酚聚氧乙基醚)、农乳700#(烷基酚甲醛树脂聚氧乙基醚)、农乳1600#(苯乙基酚聚氧乙基聚丙烯基醚)、聚氧化烯基烷基芳基醚和环氧乙烷-环氧丙烷嵌段共聚物中的至少一种。
所述分散剂具体可选自聚羧酸盐、木质素磺酸盐、烷基酚聚氧乙烯甲醛缩合物硫酸盐、烷基苯磺酸钙盐、苯磺酸甲醛缩合物钠盐、硫酸月桂酸钠，磺化蓖麻油钠盐、磺酸烷基芳基酯钠，烷基酚聚氧乙烯嘧、脂肪酸聚氧乙烯酯和酯聚氧乙烯嘧中的至少一种。
所述润湿剂具体可选自十二烷基硫酸钠、十二烷基苯磺酸钠、拉开粉BX、皂角粉、蚕沙和无患子粉中的至少一种。
所述渗透剂具体可选自硅氧烷聚氧乙烯醚、磺酸烷基芳酯、醇醚琥珀酸盐和酚醚琥珀酸盐中的至少一种。
当然，本发明所述杀菌剂和/或杀虫剂组合物中，还可适当添加其他助剂。
所述其他助剂的添加量为农业上用杀菌剂和/或杀虫剂中可接受的量即可。
所述其他助剂可选自崩解剂、消泡剂、抗冻剂和增稠剂中的至少一种。
所述崩解剂选自膨润土、尿素、硫酸铵、氯化铝和葡萄糖中的至少一种。
所述消泡剂选自硅油、硅酮类化合物、C10-C20饱和脂肪酸类化合物、C8-C10脂肪醇类化合物中的至少一种。
所述抗冻剂选自乙二醇、丙二醇、丙三醇和聚乙二醇中的至少一种。
所述增稠剂选自黄原酸胶、聚乙烯醇和聚乙二醇中的至少一种。
本发明所制备得到的杀菌剂和/或杀虫剂组合物中，可按照本领域技术人员所公知的方法，加入相应成分，从而制备得到可湿性粉剂、粉剂、颗粒剂、浓乳剂、乳油，悬浮剂、气雾剂或烟雾剂等多种剂型。
同时，可根据不同的作物及病害施用有效量的本发明的杀菌剂和/或杀虫剂组合物，可用叶面喷雾、种子处理或土壤处理的方法实施。
在某些方面，可在本发明的杀菌剂和/或杀虫剂组合物中加入一种或多种其它杀菌剂，使其产生附加的优点和效果；亦可将式I所示化合物与其它杀菌剂和/或杀虫剂混用。
此外，本发明所提供的式I所示化合物及其组合物在制备植物杀菌剂和/或杀虫剂中的应用也属于本发明的保护范围。
本发明的式I所示化合物具有广谱而优异的杀菌活性，可用于防治在多种作物上由四大致病真菌纲：子囊菌、担子菌、半知菌和卵菌纲病害引起的病害。在很低的剂量下即可获得很好的防治效果。同时，该类式I所示化合物具有一定的内吸性并可用作叶面和土壤杀菌剂，防治多种作物上的病害。具体可防止如下病害：辣椒疫病、番茄早疫病、番茄晚疫病、水稻稻瘟病、小麦叶斑病、苹果轮纹病、水稻纹枯病、水稻稻瘟病、水稻稻曲病、水稻恶苗病、小麦白粉病、油菜菌核病、黄瓜霜霉病、黄瓜枯萎病、黄瓜灰霉病、黄瓜白粉病或苹果白粉病。
此外，本发明的部分式I所示化合物还具有较好的杀虫和杀螨活性，如：Ia-84、Id-397、Ih-259等，可用于防治多种作物上害虫和螨。
本发明制备得到苄基腙类化合物的侧链为苄基腙结构，该苄基腙类化合物及含其的组合物在小剂量下即可防治植物(如：农作物：辣椒、番茄、水稻、小麦、苹果、油菜和黄瓜等)有害真菌和害虫(如：粘虫、小菜蛾、桃蚜和朱砂叶螨等)，具有广谱而优异的杀菌和杀虫效果。
附图说明
图1为式I所示化合物的制备流程图。
实施发明的最佳方式
下面通过具体实施例对本发明进行说明，但本发明并不局限于此。
下述实施例中所述实验方法，如无特殊说明，均为常规方法；所述试剂和材料，如无特殊说明，均可从商业途径获得。
一、式I所示化合物的制备实施例如下：相应的制备流程图如图1所示：
实施例1、制备化合物Ia-4：
在100mL三口瓶中加入含有0.93g(6.9mmol)1-苯亚甲基-2-甲基肼(1-benzylidene-2-methylhydrazine)的DMF溶液15mL，降温至5℃以下，加入0.53g(12mmol)质量分数为70％NaH油分散粒剂，搅拌1h后，加入(E)-2-(2-溴甲基)苯基-2-甲氧亚氨基乙酸甲酯2.35g(8.2mmol)，升温至室温(25℃)继续反应8h。加水淬灭，有灰色固体析出，柱层析得白色粉末2.2g，产率82％，熔点78-80℃。
1H NMR(300MHz,CDCl3)δ，2.93(s,3H),3.04(s,3H),3.75(s,3H),3.81(s,3H),3.85(s,2H),7.22-7.95(m,9H),8.11(s,1H).
13C NMR(75MHz,CDCl3)δ23.0,44.2,50.6,59.1,60.2,104.6,126.2,126.8,127.4,128.2,128.6,128.9,130.8,133.0,137.5,158.4,164.0,168.5.
编号Ia-1～Ia-14至Id-1～Id-14的化合物均按实施例1中的方法制备得到。
其中，化合物Ia-11：灰白色粉末，产率为77％，熔点77-79℃，1H NMR和13C NMR如下：
1H NMR(300MHz,CDCl3)δ1.23(S,9H),2.95(s,3H),3.77(S,3H),3.80(s,3H),3.81(s,2H),7.21-7.89(m,9H),8.13(s,1H).
13C NMR(75MHz,CDCl3)δ17.7,28.1,52.5,52.8,60.0,77.2,104.6,126.2,126.8,127.4,128.4,128.8,128.9,130.5,131.1,133.6,137.2,158.4,164.0,168.8。
化合物Ib-11：白色粉末，熔点102-104℃，产率为82％，1H NMR和13C NMR如下：
1H NMR(300MHz,CDCl3)δ1.27(s,9H),2.73(s,3H),2.95(s,3H),3.80(s,3H),3.81(s,2H),7.21-7.95(m,9H),8.01(s,1H).
13C NMR(75MHz,CDCl3)δ17.5,26.3,28.7,51.4,59.8,77.6,104.1,126.1,126.8,127.9,128.0,128.8,128.9,130.7,131.2,133.4,137.6,158.4,168.2,172.5。
化合物Ic-11：淡黄色粉末，熔点86-88℃，产率为73％，1H NMR和13C NMR如下：
1H NMR(300MHz,CDCl3)δ1.28(s,9H),2.97(s,3H),3.72(s,3H),3.80(s,2H),3.96(s,3H),7.24-7.96(m,9H)；
13C NMR(75MHz,CDCl3)δ17.3,28.3,52.5,52.7,64.3,77.4,123.0,125.3,127.1,128.2,128.8,130.8,131.0,131.1,131.7,137.5,149.7,163.7,168.8。
化合物Id-11：白色粉末，熔点108-110℃，产率为89％，1H NMR和13C NMR如下：
1H NMR(300MHz,CDCl3)δ1.32(s,9H),2.66(s,3H),2.98(s,3H),3.82(s,2H),3.96(s,3H),7.50-7.93(m,9H)；
13C NMR(75MHz,CDCl3)δ17.8,26.2,28.6,64.4,77.5,123.7,125.0,127.4,128.2,128.6,130.8,131.2,131.4,131.9,137.1,151.7,164.2,168.8。
实施例2：制备化合物Ic-109：
在100ml三口瓶中加入2-(1-(4-氯苯基)亚乙基)肼基羧酸乙酯(0.5g,0.0021mol)，DMF 15mL，降温至5℃以下，加入0.13g(0.00315mol)质量分数为70％NaH油分散粒剂，搅拌1h，后加入(E)-2-(2-溴甲基)苯基-2-甲氧亚氨基乙酸甲酯0.72g(0.0025mol)，升温至室温(25℃)继续反应9h,加水淬灭，有固体析出，柱层析得淡黄色固体0.71g，产率77％，熔点123-125℃，1H NMR和13C NMR如下：
1H NMR(300MHz,DMSO)δ7.80(d,J＝8.6Hz,2H),7.50(d,J＝8.6Hz,2H),7.39～7.34(m,,3H),7.16～7.15(m,1H),4.62(s,2H),4.08(q,J＝7.0Hz,2H),3.93(s,3H),3.66(s,3H),1.99(s,3H),1.17(t,J＝7.1Hz,3H).
13C NMR(75MHz,DMSO)δ169.65,162.93,152.44,148.94,135.86,135.80,135.61,130.08,129.42,128.88,128.71,128.65,127.38,63.52,61.89,52.65,52.20,40.62,40.34,40.07,39.79,39.51,39.23,38.95,16.82,14.56.
编号Ia-15～Ia-264至Id-15～Id-264、Ie-1～Ie-240至Ih-1～Ih-240的化合物均按实施例2中的方法制备得到。
其中，化合物Ic-228：白色粉末，熔点126-128℃，产率为70％，1H NMR和13C NMR如下：
1H NMR(300MHz,DMSO)δ8.26(d,J＝9.1Hz,2H),8.01(d,J＝9.1Hz,2H),7.42–7.26(m,3H),7.14(m,1H),4.64(s,2H),3.93(s,3H),3.66(s,3H),2.04(s,3H),1.39(s,9H).
13C NMR(75MHz,DMSO)δ168.25,162.95,151.06,148.96,148.65,143.16,135.95,130.09,129.37,128.88,128.72,128.27,127.37,123.72,81.12,63.55,52.67,27.99,17.35.
化合物Ic-259：白色固体，熔点149-151℃，产率为79％，1H NMR和13C NMR如下：
1H NMR(300MHz,CDCl3)δ8.38–8.30(m,1H),8.14～8.12(m,1H),8.02～7.99(m,1H),7.53～7.50(m,2H),7.42–7.29(m,2H),7.17～7.13(m,2H),4.99(s,2H),4.14(s,3H),3.96(s,3H),1.62(s,9H).
13C NMR(75MHz,DMSO)δ163.07,152.96,148.75,148.39,138.12,136.76,133.58,132.69,130.62,129.93,129.51,128.84,127.47,125.78,123.82,120.84,81.92,63.77,52.97,45.88,28.02.
化合物If-222：白色固体，熔点162-164℃，产率为76％，1H NMR和13C NMR如下：
1H NMR(300MHz,CDCl3)δ1.38(s,9H),2.95(s,3H),3.68(s,3H),3.93(s,3H),6.10(s,2H),7.10-7.71(m,5H),8.54(d,1H),9.04(d,1H)；
13C NMR(75MHz,DMSO)δ17.3,28.5,51.4,52.8,64.1,84.4,121.5,124.3,125.0,125.2,126.8,130.0,130.6,136.9,139.1,149.7,152.4,153.4,154.7,163.5,168.8.
实施例3、制备化合物If-283：
在100ml三口瓶中加入(0.5g,2.3mmol)2-((6-氯吡啶-3-基)亚甲基)-1- 腈基肼，DMF 15mL，降温至5℃以下，加入0.12g(3.3mmol)质量分数为70％NaH油分散粒剂，搅拌1h后加入0.79g(2.8mmol)(E)-2-(2-溴甲基)苯基-2-甲氧亚氨基乙酸甲酯，升温至室温(25℃)继续反应5h。加水淬灭，有固体析出，柱层析纯化得黄色粉末0.73g，产率80％，熔点170-172℃，1H NMR和13C NMR如下：
1H NMR(300MHz,DMSO)δ8.69(d,J＝1.9Hz,1H),8.12(dd,J＝8.4,2.6Hz,1H),7.60(d,J＝8.5Hz,1H),7.50-40(m,3H),7.26-7.21(m,1H),4.60(s,2H),3.94(s,3H),3.70(s,3H),2.38(s,3H).
13C NMR(75MHz,DMSO)δ162.86,162.06,152.22,148.84,148.43,137.94,132.94,131.80,130.82,130.23,129.73,129.20,128.65,124.39,112.95,63.72,58.31,52.86,15.96.
编号Ia-265～Ia-330至Id-265～Id-330、Ie-241～Ie-301至Ih-241～Ih-301的化合物均按实施例3中的方法制备得到。
其中，化合物Ic-296：白色固体，熔点156-158℃，产率为71％，1H NMR和13C NMR如下：
1H NMR(300MHz,DMSO)δ7.71-7.58(m,2H),7.54-7.35(m,,6H),7.31–7.14(m,1H),4.57(s,2H),3.94(s,3H),3.70(s,3H),2.35(s,3H).
13C NMR(75MHz,DMSO)δ165.61,162.85,148.87,136.54,133.09,130.94,130.83,130.17,129.68,129.19,128.74,128.56,127.03,113.53,63.70,58.18,52.82,16.22.
化合物Ic-315：白色固体，熔点172-174℃，产率为73％，1H NMR和13C NMR如下：
1H NMR(300MHz,DMSO)δ7.91(d,J＝8.3Hz,2H),7.80(d,J＝8.3Hz,2H),7.55～7.49(m,3H),7.29～7.26(m,1H),4.62(s,2H),3.94(s,3H),3.70(s,3H),2.40(s,3H).
13C NMR(75MHz,DMSO)δ163.73,162.85,148.85,140.46,132.96,130.94,130.81,130.52,130.15,129.71,129.22,128.62,127.85,126.00,125.67,125.62,122.39,112.97,63.70,58.38,52.65,16.33.
实施例4、制备化合物Ic-361：
在100mL三口瓶中加入含有0.41g(2.3mmol)2-(1-苯基亚乙基)肼基甲 酰胺的DMF溶液15mL，降温至5℃以下，加入0.12g(3.3mmol)质量分数为70％NaH油分散粒剂，搅拌1h后加入0.79g(2.8mmol)(E)-2-(2-溴甲基)苯基-2-甲氧亚氨基乙酸甲酯，升温至室温(25℃)继续反应4h。加水淬灭，有固体析出，柱层析纯化得白色粉末，产率65％，熔点184-186℃，1H NMR和13C NMR如下：
1H NMR(300MHz,DMSO)δ2.93(s,3H),3.62(s,3H),3.95(s,3H),5.92(s,2H),7.12-7.86(m,9H),8.11(bs,2H)；
13C NMR(75MHz,DMSO)δ19.3,51.2,52.8,64.4,122.7,125.6,126.8,128.0,129.0,130.5,130.8,131.1,136.9,137.4,149.0,155.2,163.3,170.0.
编号Ia-331～Ia-394至Id-331～Id-394、Ie-302～Ie-362至Ih-302～IH-362的化合物均按实施例4中的方法制备得到。
其中化合物Ia-336：白色固体，产率74％，mp 207-209℃，1H NMR和13C NMR如下：
1H NMR(300MHz,DMSO)δ3.23(s,3H),3.76(s,3H),6.31(s,2H),7.18-7.75(m,10H),8.41(bs,1H)；
13C NMR(75MHz,DMSO)δ49.5,50.6,59.1,104.7,125.6,126.5,127.7,128.2,129.1,129.8,130.0,130.6,133.5,134.6,143.5,155.4,158.2,164.7.
化合物Ie-331：白色固体，产率56％，mp 241-243℃，1H NMR和13C NMR如下：
1H NMR(300MHz,DMSO)δ3.36(s,3H),3.62(s,3H),3.77(s,3H),6.34(s,2H),7.03(s,1H),7.21-7.74(m,9H),8.49(s,1H)；
13C NMR(75MHz,DMSO)δ49.4,50.3,54.1,59.5,104.2,115.6,116.2,126.2,126.6,127.7,129.9,134.1,134.6,140.5,146.9,155.3,157.1,158.3,164.5.
实施例5、制备化合物Ic-400：
在100mL三口瓶中加入含有0.64g(2.3mmol)2-(1-(4-氯苯基)亚乙基)肼基硫代甲酰胺的DMF 15mL，降温至5℃以下，加入0.12g(3.3mmol)质量分数为70％NaH油分散粒剂，搅拌1h后加入0.79g(2.8mmol)(E)-2-(2-溴甲基)苯基-2-甲氧亚氨基乙酸甲酯，升温至室温(25℃)继续反应4h。加水淬灭，有白色固体析出，柱层析，得白色粉末，产率72％，熔点 178-180℃，1H NMR和13C NMR如下：
1H NMR(300MHz,DMSO)δ2.90(s,3H),3.58(s,3H),3.63(s,3H),5.69(s,2H),7.21-7.86(m,8H),8.01(bs,2H)；
13C NMR(75MHz,DMSO)δ20.3,52.0,56.4,64.0,121.4,125.3,126.5,128.1,128.8,130.0,130.7,135.4,136.8,136.9,149.2,163.6,170.1,176.6.
编号Ia-395～Ia-402至Id-395～Id-402的化合物均按实施例5中的方法制备得到。
其中化合物Ia-400：白色固体，产率70％，mp 211-213℃，1H NMR和13C NMR如下：
1H NMR(300MHz,DMSO)δ2.95(s,3H),3.53(s,3H),3.72(s,3H),5.60(s,2H),7.12(s,1H),7.20-7.94(m,8H),8.41(bs,2H)；
13C NMR(75MHz,DMSO)δ21.1,50.7,57.2,59.6,105.0,126.0,126.4,127.3,128.2,128.9,129.9,132.5,134.1,135.6,136.6,158.4,164.3,170.0,176.2.
化合物Ic-397：白色固体，产率64％，mp 257-259℃，1H NMR和13C NMR如下：
1H NMR(300MHz,DMSO)δ3.64(s,3H),4.00(s,3H),5.85(s,2H),7.23-8.62(m,11H).
13C NMR(75MHz,DMSO)δ50.7,56.6,64.3,121.5,123.7,124.0,124.9,126.0,129.6,131.1,136.3,139.3,146.2,149.7,150.0,163.5,176.0.
实施例6、制备化合物Ic-404：
在100ml三口瓶中加入含有0.58g(2.3mmol)N'-(1-(4-氯苯基)亚乙基)特戊酰肼的MF 15mL，降温至5℃以下，加入0.12g(3.3mmol)质量分数为70％NaH油分散粒剂，搅拌1h后加入0.79g(2.8mmol)(E)-2-(2-溴甲基)苯基-2-甲氧亚氨基乙酸甲酯，升温至室温(25℃)继续反应4h。加水淬灭，有白色固体析出，柱层析，得白色粉末，产率46％，熔点148-150℃，1H NMR和13C NMR如下：
1H NMR(300MHz,CDCl3)δ1.24(s,9H),2.90(s,3H),3.65(s,3H),3.88(s,3H),6.04(s,2H),7.20-7.88(m,8H)；
13C NMR(75MHz,CDCl3)δ20.0,28.6,39.5,50.7,52.7,64.3,122.0, 125.3,126.8,128.2,128.9,130.1,130.8,135.6,136.6,136.9,149.7,163.7,170.1,183.0.
编号Ia-403～Ia-405至Id-403～Id-405的化合物均按实施例6中的方法制备得到。
其中化合物Ic-403：白色固体，产率78％，mp 195-197℃，1H NMR和13C NMR如下：
1H NMR(300MHz,CDCl3)δ2.16(s,3H),2.91(s,3H),3.66(s,3H),3.92(s,3H),6.14(s,2H),7.21-7.954(m,9H).
13C NMR(75MHz,CDCl3)δ20.0,24.6,49.4,52.8,64.5,120.9,125.2,126.5,128.0,128.4,130.0,130.7,130.9,136.3,136.9,149.1,163.0,168.2,170.3.
化合物Id-403：白色固体，产率68％，mp 207-209℃，1H NMR和13C NMR如下：
1H NMR(300MHz,CDCl3)δ2.14(s,3H),2.77(s,3H),3.00(s,3H),3.92(s,3H),6.19(s,2H),7.28-8.06(m,10H).
13C NMR(75MHz,CDCl3)δ20.2,24.9,26.0,49.8,63.8,120.6,125.0,126.1,128.2,128.7,130.5,131.1,132.8,136.3,137.2,151.4,163.6,168.7,170.3.
二、包含式I所示化合物的组合物的实施例如下：(以下各组分均以重量百分含量计，活性组分折百后计量加入)
实施例7、制备含有50％式I所示化合物的可湿性粉剂：
可湿性粉剂的组成：式I所示化合物50％、分散剂聚羧酸盐5％、润湿剂十二烷基硫酸钠3％、固体载体或崩解剂膨润土42％；将各组分按所述比例混合得到混合物，对其进行气流粉碎，即可制得50％可湿性粉剂。
实施例8、制备含有30％式I所示化合物的乳油：
乳油的组成：式I所示化合物30％、乳化剂聚氧化烯基烷基芳基醚12％、渗透剂磺酸烷基芳酯10％、液体载体环己酮48％；将各组分按所述比例混合得到30％化合物的透明溶液。
实施例9、制备含有60％式I化合物的水分散粒剂：
水分散粒剂的组成：式I所示化合物70％、分散剂烷基苯磺酸钙盐 3％、分散剂木质素磺酸盐3％、润湿剂十二烷基硫酸钠4％、固体载体或填料淀粉20％；将各组分按所述比例混合制得70％式I化合物的水分散粒剂。
三、生物活性测定：
实施例10、杀菌活性测定：
用本发明式I化合物对植物的各种菌病害进行试验，试验方法如下：采用活体盆栽测定方法：将待测的式I化合物原药(即纯的式I化合物)用少量N,N-二甲基甲酰胺溶解，用水稀释至所需刻度，涉及实验组和对照组：实验组为喷雾施药到植物试材上，24h后进行病害接种；对照组未喷雾施药到植物试材上，24h后进行病害接种；将两组植物试材均放置于恒温恒湿(25±2℃，相对湿度60％)培养箱中，使感染继续，待对照组充分发病后(通常为一周)，进行评估调查，部分测试结果如下：
当喷雾施药剂量为500ppm时，Ia-1～Id-1至Ia-405～Id-405中的大部分化合物对辣椒疫病和小麦白粉病的防效为100％，当喷雾施药剂量为50ppm时，Ia-1～Id-1至Ia-405～Id-405的化合物防效为70-100％。
当喷雾施药剂量为100ppm时，化合物Ia-66、Ia-87、Ib-75、Ic-124、Ic-299、Id-238、If182、Ig217、Ih-261、Ij-53等对辣椒疫病和小麦白粉病的防效均为100％，防效的计算公式如下：
防效＝(1-药剂处理后病情指数/空白对照病情指数)×100％
选取Ic-299与现有产品嘧菌酯分别作其杀菌活性试验，试验结果如下表1所示：
表1、杀菌活性对比试验结果
Figure PCTCN2015000489-appb-000034
当喷雾施药剂量为50ppm时，化合物Ia-87、Ic-124、Ih-261对番茄早疫病、水稻稻瘟病、小麦叶斑病、苹果轮纹病、水稻纹枯病、水稻稻瘟病、水稻稻曲病、水稻恶苗病、油菜菌核病、黄瓜霜霉病、黄瓜灰霉病和黄瓜白粉病的防效均超过80％。
实施例11、杀虫杀螨活性测定：
对昆虫和螨类进行了杀虫活性测定，测定的方法如下：将式I化合物用少量N,N-二甲基甲酰胺溶解，用水稀释至所需刻度；
以粘虫、小菜蛾、桃蚜和朱砂叶螨为供试材料，用airbrush喷雾法进行杀虫活性测定，airbrush喷雾处理的压力为10psi，喷液量为0.5ml。处理后2-3日后，调查供试材料的死亡率，部分测试结果如下：
当airbrush喷雾法的施药剂量为500ppm时，化合物Ic-315、Ih246、Id-374对粘虫、小菜蛾、桃蚜、朱砂叶螨死亡率均超过60％。
工业应用
本发明提供的式I所示化合物具有广谱而优异的杀菌活性，可用于防治在多种作物上由四大致病真菌纲：子囊菌、担子菌、半知菌和卵菌纲病害引起的病害。在低剂量下即可获得很好的防治效果，在植物杀菌剂和/或杀虫剂中有广泛的应用。

Claims (10)

  1. 式I所示化合物：
    Figure PCTCN2015000489-appb-100001
    所述式I中，X选自CH或N；Y选自O、S和NH中的任一种；R1选自C1-C8的烷基、烯丙基、炔丙基、苄基、苯甲酰基、C1～C5的脂肪酰基、C1～C5的烷氧羰基、氰基、氨基甲酰基和硫代氨基甲酰基中的任一种；R2选自C1-C12烷基、Q1和Q2中的任一种；R3选自氢、C1-C5的烷基、Q1和Q2中的任一种；
    Figure PCTCN2015000489-appb-100002
    其中，所述Q1和Q2中，R4和R5均选自氢、C1-C5的烷基、C1-C5的烷氧基、C1-C5的氟代烷基、C1-C5的氟代烷氧基、卤素、硝基、氰基、苯氧基、吡啶氧基、甲磺酰基和三氟甲磺酰基中的至少一种，所述卤素选自氟、氯、溴和碘中的任一种；m＝0-5；n＝0-4；
    R4的结合位点为剩余的5个结合位点中的至少一个，其中，当m>1时，R4相同或不同；R5的结合位点为剩余4个结合位点中的至少一个，其中，当n>1时，R5相同或不同，其中，Q2中，N位于2、3和4位中的任一处。
  2. 根据权利要求1所述的式I所示化合物，其特征在于：所述式I中，Y选自O或NH；R1选自C1～C4的直链或支链烷氧羰基、苯甲酰基、氰基、氨基甲酰基和硫代氨基甲酰基中的任一种；R2选自Q1或Q2；R3选自氢或C1-C2的烷基；
    其中，所述Q1和Q2中，R4和R5均选自C1-C5的烷基、三氟甲基、三氟甲氧基、苯氧基、卤素、硝基、氰基、吡啶氧基、甲磺酰基和三氟甲磺酰基中的至少一种；m＝0-3，n＝0-2。
  3. 根据权利要求2所述的式I所示化合物，其特征在于：所述式I 中，R1选自C1～C4的直链或支链烷氧羰基、或者氰基；R3选自氢或甲基；
    其中，所述Q1和Q2中，R4和R5均选自三氟甲基、三氟甲氧基、苯氧基、氟、氯、硝基、氰基、吡啶氧基、甲磺酰基和三氟甲磺酰基中的至少一种。
  4. 权利要求1-3中任一项所述的式I所示化合物的制备方法，包括如下步骤：在催化剂存在下，将式IV所示化合物和式V所示化合物于有机溶剂中进行缩合反应，得到式I所示化合物；
    Figure PCTCN2015000489-appb-100003
    所述式IV中，R1、R1和R3的定义均同式I；所述式V中，X和Y的定义均同式I。
  5. 根据权利要求4所述的式I所示化合物的制备方法，其特征在于：所述催化剂为碱，所述碱选自氢化钠、氨基钠、氨基锂、二异丙基氨基锂、正丁基锂和苯基锂中的至少一种；
    所述催化剂和式IV所示化合物的摩尔比为1:(1.2～3)；
    所述缩合反应的反应温度为-5～100℃，反应时间为2-12h；所述式IV所示化合物和式V所示化合物的摩尔比为1：(1-2)；
    所述有机溶剂选自N,N-二甲基甲酰胺、N-甲基吡咯烷酮和乙二醇二甲醚中的至少一种。
  6. 根据权利要求4或5所述的式I所示化合物的制备方法，其特征在于：所述缩合反应按如下步骤进行：将催化剂和式IV所示化合物在有机溶剂中，于-10-5℃下搅拌0.5-2h，再向其中加入式V所示化合物于-5～100℃下反应2-12h，得到式I所示化合物；
    式IV所示化合物按如下方法制备得到：将式II所示化合物和式III所示化合物于有机溶剂中进行反应，得到式IV所示化合物；
    Figure PCTCN2015000489-appb-100004
    Figure PCTCN2015000489-appb-100005
    所述式II中，R1的定义同式I；所述式III中，R2和R3的定义均同式I；
    其中，II所示化合物和式III所示化合物的摩尔比为1：(1-2)；
    所述反应的反应温度为-20～50℃，反应时间为1-6h；
    所述有机溶剂为甲醇或乙醇。
  7. 一种组合物，包括权利要求1-3中任一项所述的式I所示化合物和农业上可接受的载体，其中，该组合物中式I所示化合物的重量百分含量为0.1～99％。
  8. 根据权利要求7所述的组合物，其特征在于：所述农业上可接受的载体选自固体载体和/或液体载体；
    所述固体载体选自天然或合成的硅酸盐、硫酸铵、硫酸钙、氧化硅酸铝、天然或合成的树脂、多氯苯酚、淀粉、膨润土和蜡中的至少一种，其中，所述天然或合成的硅酸盐选自硅镁土、滑石、硅酸铝、硅藻土、云母、蒙脱石和硅酸钙中的至少一种，所述天然或合成的树脂选自苯并呋喃树脂、苯乙烯聚合物和苯乙烯共聚物中的至少一种；所述蜡选自蜂蜡和/或石蜡；
    所述液体载体选自水、C1-C4的醇、C3-C8的酮、芳烃、石油馏分和C6-C12的氯代烃中的至少一种，其中，所述醇为乙醇和/或乙二醇；所述酮为苯乙酮、丙酮、甲乙酮和环己酮中的至少一种；所述芳烃为苯、甲苯和二甲苯中的至少一种；所述石油馏分为煤油和/或矿物油；所述氯代烃为四氯化碳、二氯甲烷和三氯乙烷中的至少一种。
  9. 根据权利要求7或8所述的组合物，其特征在于：所述组合物中，还包括表面活性剂；
    所述表面活性剂选自乳化剂、分散剂、润湿剂和渗透剂中的至少一种；
    所述乳化剂选自烷基苯黄酸钙，苯基酚聚氧乙基醚、烷基酚甲醛树脂聚氧乙基醚、苯乙基酚聚氧乙基聚丙烯基醚、聚氧化烯基烷基芳基醚和环氧乙烷-环氧丙烷嵌段共聚物中的至少一种；
    所述分散剂选自聚羧酸盐、木质素磺酸盐、烷基酚聚氧乙烯甲醛缩合 物硫酸盐、烷基苯磺酸钙盐、苯磺酸甲醛缩合物钠盐、硫酸月桂酸钠，磺化蓖麻油钠盐、磺酸烷基芳基酯钠，烷基酚聚氧乙烯嘧、脂肪酸聚氧乙烯酯和酯聚氧乙烯嘧中的至少一种；
    所述润湿剂选自十二烷基硫酸钠、十二烷基苯磺酸钠、拉开粉BX、皂角粉、蚕沙和无患子粉中的至少一种；
    所述组合物中，还包括其他助剂；
    所述其他助剂选自崩解剂、消泡剂、抗冻剂和增稠剂中的至少一种；
    所述崩解剂选自膨润土、尿素、硫酸铵、氯化铝和葡萄糖中的至少一种；
    所述消泡剂选自硅油、硅酮类化合物、C10-C20饱和脂肪酸类化合物、C8-C10脂肪醇类化合物中的至少一种；
    所述抗冻剂选自乙二醇、丙二醇、丙三醇和聚乙二醇中的至少一种；
    所述的增稠剂选自黄原酸胶、聚乙烯醇和聚乙二醇中的至少一种。
  10. 权利要求1-3中任一项所述的式I所示化合物和/或权利要求7-9中任一项所述的组合物在制备植物杀菌剂和/或杀虫剂中的应用。
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