WO2010075760A1 - 具有杀虫活性的含氮杂环化合物、其制备及用途 - Google Patents

具有杀虫活性的含氮杂环化合物、其制备及用途 Download PDF

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WO2010075760A1
WO2010075760A1 PCT/CN2009/076131 CN2009076131W WO2010075760A1 WO 2010075760 A1 WO2010075760 A1 WO 2010075760A1 CN 2009076131 W CN2009076131 W CN 2009076131W WO 2010075760 A1 WO2010075760 A1 WO 2010075760A1
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group
compound
cis
acceptable salt
alkyl
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PCT/CN2009/076131
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English (en)
French (fr)
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李忠
钱旭红
杨小宝
徐晓勇
陶黎明
宋恭华
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华东理工大学
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    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D417/00Heterocyclic 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
    • C07D417/02Heterocyclic 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
    • C07D417/04Heterocyclic 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
    • AHUMAN NECESSITIES
    • A01AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01NPRESERVATION 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
    • A01N43/00Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds
    • A01N43/34Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with one nitrogen atom as the only ring hetero atom
    • A01N43/40Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with one nitrogen atom as the only ring hetero atom six-membered rings
    • AHUMAN NECESSITIES
    • A01AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01NPRESERVATION 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
    • A01N43/00Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds
    • A01N43/72Biocides, 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
    • A01N43/74Biocides, 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 1,3
    • A01N43/781,3-Thiazoles; Hydrogenated 1,3-thiazoles
    • AHUMAN NECESSITIES
    • A01AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01NPRESERVATION 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
    • A01N43/00Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds
    • A01N43/90Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having two or more relevant hetero rings, condensed among themselves or with a common carbocyclic ring system
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D471/00Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
    • C07D471/02Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
    • C07D471/04Ortho-condensed systems

Definitions

  • Nitrogen-containing heterocyclic compound having insecticidal activity preparation thereof and use thereof
  • the invention relates to a novel insecticide of neonicotinoid type, a preparation method and application thereof.
  • Another object of the invention is to provide protection for growing and harvested crops from insect attack and infestation.
  • is a five- or six-membered heterocyclic group containing nitrogen, oxygen and/or sulfur, a halogenated five- or six-membered heterocyclic group containing nitrogen, oxygen and/or sulfur, or a substituted or unsubstituted phenyl group, Wherein the substituent is one or more selected from the group consisting of 1-3; such as: halogen, d- 4 haloalkyl or d- 4 chloroalkoxy;
  • R 2 and R 3 are each independently H, d- 6 alkyl, allyl, benzyl, alkoxyalkyl having 2 to 4 C, alkoxycarbonyl having 1 to 3 C, phenoxy Carbonyl group, having 2-6 C alkynylcarbonyl groups, having 2 to 3 C alkenylcarbonyl groups, having 3 to 6 C cycloalkylcarbonyl groups, benzoyl or substituted benzoyl groups, furancarbonyl groups, or ⁇ , ⁇ -dimethylcarbonyl, or R 2 and R 3 together form -CH 2 -CH 2 - or -CH 2 -CH 2 -CH 2 -; -CH 2 -XR-CH 2 -, wherein X is a hetero atom selected from N, 0 or S, and R is a d. 6 alkyl or alkoxy group on a hetero atom;
  • R 4 is H, d 6 alkyl, allyl, alkenyl, benzyl, 5- or 6-membered heterocyclic group containing nitrogen, oxygen and/or sulfur, 3 ⁇ 4 generation of nitrogen, oxygen and/or sulfur a five- or six-membered heterocyclic group, or a substituted or unsubstituted phenyl group;
  • Y is nitro, cyano, trifluoromethyl, trifluoroacetyl, or trifluoromethanesulfonyl
  • Z is nitro, cyano, ester, amide, methylcarboxy, methylhydroxy, or trifluoromethyl.
  • it is selected from the group consisting of pyridyl, thiazolyl, pyrimidinyl, tetrahydrofuranyl, oxazolyl, or a halogen thereof.
  • a halogenated pyridyl group, a halogenated thiazolyl group, a halogenated pyrimidinyl group, a halogenated tetrahydrofuranyl group, or a halogenated oxazolyl group more preferably the halogenated product is a chlorinated product.
  • R 2 , R 3 are hydrogen or Cw alkyl, or together form -CH 2 -CH 2 - or -CH 2 -CH 2 -CH 2 -, -CH2-XR-CH2- Wherein X is a hetero atom such as N, 0, S, and R is a C1-6 alkyl or alkoxy group on the hetero atom.
  • R 2 , R 3 are hydrogen or CM alkyl, preferably hydrogen, methyl or ethyl, or together with R 3 form -CH 2 -CH 2 - or -CH 2 -CH 2 -CH 2 -.
  • R 4 is H, d- 6 alkyl, substituted or unsubstituted pyridyl, thiazolyl, pyrimidinyl, tetrahydrofuranyl, oxazolyl, or substituted or unsubstituted phenyl.
  • R 4 is a differently substituted phenyl group.
  • R 5 , R 6 are hydrogen, sulfonyl, or carbonyl. In a preferred embodiment, R 5 and R 6 are hydrogen.
  • Y is a nitro group or a cyano group.
  • Y is a nitro group.
  • Z is nitro, cyano, ester, or trifluoromethyl.
  • Y is cyano, trifluoromethyl or ester.
  • an agricultural composition comprising:
  • component (a) comprises from 0.01 to 99.9% by weight, preferably from 0.05 to 90% by weight, of the agricultural composition.
  • the agricultural composition is used to kill or prevent pests selected from the group consisting of Coleoptera, Lepidoptera, Hemiptera, Orthoptera, Isoptera or Diptera.
  • the pest has a sucking or sucking mouthpart.
  • the pest is aphid, planthopper, whitefly, spider mites, thrips, cotton bollworm, cabbage caterpillar, diamondback moth, Spodoptera litura, or armyworm.
  • the agricultural composition further comprises other active substances selected from the group consisting of: insecticides, baits, fungicides, acaricides, nematicides, fungicides or growth control Agent.
  • a third aspect of the invention there is provided the use of the above agricultural composition of the invention for killing or preventing agricultural pests, sanitary pests and pests harmful to animal health; or for killing or preventing agricultural pests, sanitary pests And insecticide compositions that are harmful to animal health.
  • a pesticidal and/or pest control method comprising applying the above agricultural composition to a plant body that is or may be subject to pests, soil surrounding the environment or environment.
  • a compound of the invention an optical isomer, a cis-trans isomer or a pesticide-acceptable salt thereof, or a combination thereof, in the preparation of a pesticide composition.
  • a process for the preparation of the above-mentioned compound, optical isomer, cis-trans isomer or agrochemically acceptable salt thereof comprising: formulating the formula I in the presence of a catalyst The compound, the compound of the formula II and the compound of the formula III are reacted in a reaction solvent at a reaction temperature for a certain period of time to obtain a compound of the formula A: Wherein R 2 , R 3 , R 4 , Y and Z are as defined above.
  • reaction solvent is water, ethanol, methanol, acetonitrile, dimethyl sulfoxide, hydrazine, hydrazine-dimethylformamide, formic acid, acetic acid.
  • reaction solvent is selected from acetonitrile or ethanol, preferably ethanol.
  • reaction temperature is from 0 to 200 °C.
  • reaction time is from 3 to 24 hours.
  • the catalyst is a proline or proline derivative, piperidine, DBU, DMAP, triethylamine, diisopropylethylamine, pyridine or a substituted pyridine, hydrochloric acid, formic acid , acetic acid, boron trifluoride, aluminum trichloride, ferric chloride.
  • the catalyst is selected from the group consisting of concentrated hydrochloric acid, valine or piperidine, preferably piperidine.
  • the method comprises the steps of: using 10% piperidine in an ethanol solution, performing the following reaction for 3-24 hours under reflux conditions, and then performing alkylation under an organic base condition to obtain Compound of formula A:
  • a process for the preparation of the agricultural composition of the second aspect of the invention comprising the steps of: (a) the compound of the first aspect of the invention, its optical isomer, Isomers or agrochemically acceptable salts, or combinations thereof; mixed with (b) an agriculturally acceptable carrier and/or excipient to form an agricultural composition.
  • the inventors have retained the active pharmacophore nitromethylene on the basis of the structure of the existing nitromethylene-based neonicotinoid insecticide through long-term and in-depth research, and introduced 1,4-two. Hydropyridine structure, the structure of neonicotinoid insecticides was changed, and a new class of neonicotinoid compounds was unexpectedly synthesized for the first time. The compound has significantly improved insecticidal activity and has an expanded insecticidal activity. Spectrum. On this basis, the inventors completed the present invention. Group definition
  • hydrocarbyl refers to a saturated or unsaturated group containing only carbon, hydrogen, such as alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, aryl, etc. having from 1 to 6 carbon atoms. Preferred are alkyl, alkenyl or alkynyl groups.
  • alkenyl refers to a straight or branched alkenyl group having 2 to 6 carbon atoms, such as ethenyl, allyl, 1-propenyl, isopropenyl, 1-butenyl, 2-butene Base, or a similar group.
  • alkynyl refers to a straight or branched alkynyl group having 2 to 6 carbon atoms, such as ethynyl, propynyl and the like.
  • cycloalkyl refers to cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, or cycloheptyl, and the like.
  • alkyl refers to a straight or branched alkyl group having from 1 to 6 carbon atoms, such as methyl, ethyl, propyl, isopropyl, butyl, isobutyl, sec-butyl. , tert-butyl, or the like.
  • C alkoxy refers to a straight or branched alkoxy group having from 1 to 6 carbon atoms, such as methoxy, ethoxy, propoxy, isopropoxy, butoxy, isobutyl An oxy group, a sec-butoxy group, a tert-butoxy group, or the like.
  • halogen means fluoro, chloro, bromo, or iodo.
  • halogenated refers to a group substituted with one or more of the above halogen atoms, which may be the same or different, such as a trifluoromethyl group, a pentafluoroethyl group, or the like.
  • c 5 -12 aryl refers to a monocyclic to tricyclic aromatic hydrocarbon group such as phenyl, naphthyl, or the like.
  • aralkyl refers to an alkyl group substituted with the above aryl group.
  • five- or six-membered heterocyclic group refers to a five- or six-membered ring containing one or more heteroatoms selected from nitrogen, oxygen or sulfur, such as pyridyl, thiazolyl, pyrimidinyl, tetrahydrofuranyl, or Azolyl and the like. Insecticidal activity of the active substance of the present invention
  • active substance of the invention or “active compound of the invention” means a compound of the invention, an optical isomer, a cis-trans isomer or a pesticide-accepting salt thereof, having 1,4 - dihydrogen Pyridine structure, which has significant insecticidal activity, and an expanded insecticidal spectrum.
  • agrochemically acceptable salt means that the anion of the salt is known and acceptable in forming the pharmaceutically acceptable salt of the pesticide.
  • the salt is preferably water soluble.
  • the acid addition salts formed from the compounds of formula (A) include salts formed with inorganic acids, such as hydrochlorides, phosphates, sulfates, nitrates; and salts formed from organic acids, such as acetates. , benzoate.
  • the active material of the present invention can be used for controlling and eliminating a wide range of agricultural and forestry plant pests, storing cereal pests, and public health pests.
  • insecticide is a general term for substances having the effect of controlling all the pests mentioned above.
  • pests include, but are not limited to, coleopteran insects, tw H iSUopM zeamais, Tribolium castanetmi, ⁇ Wi ⁇ (enosepilachna vigintioctomaculata), and twenty-eight ladybugs (Hewfwe zYac/ma sparsa), Fine-chested beetle ( gr/ot ⁇ / ⁇ c/co//// , Anomala cupripes, four-grain 1313 tortoise CPop ⁇ a quadri guttata), potato leaf beetle (Mo"o/3 ⁇ 4?ta hieroglyphic a) , ⁇ h . ⁇ (Monochamus alternatus) , ⁇ -(Echi oc emus squameus) , P ⁇ Ep [Basiprionota bisignata), Anoplophora chinensis, Apripona germari, Achilles tendon /i «c/co
  • Fej (A phis gossydii) , radish tooth (Jpopz/s erj ⁇ /m/ pseudobrassicae) , 3 ⁇ 43 ⁇ 43 ⁇ 4 1*3 Tabaci); Orthoptera, such as German cockroach C6/atfe ⁇ 2 germaw/ca), American cockroach ( ⁇ rp/aweto amer/caw), African cockroach (Gryllotalpa africana), or Asian cockroach (Joc m /grator/ ⁇ ); Isoptera, such as Solenopsis invicta, or Coptotermes formosanus; Diptera, such as Musca domestica, ⁇ k k. ⁇ .
  • Aedes Aegypti), ⁇ (Delia platura), - ⁇ i ⁇ Culex sp.), or Anopheles sinensis 1 ⁇ 2o; ⁇ e/ ⁇ sinensis); pests that endanger animal health, such as tiny calves Boc ⁇ /z// ⁇ microplus ), Haemaphysalis longicornis, Hyalomma anatolicum, ⁇ . ⁇ (Hpoderma spp.), liver slices ⁇ i (Fascio!a hepatica), Bayes Monitz practice ⁇ (Moniezia blanchard), 3 ⁇ 4 3 ⁇ 4 ⁇ ⁇ il (Ostertagia spp.), Hi i3 ⁇ 4 (Trypanosoma enansi, Babesia bigeminal, etc.).
  • pests that endanger animal health such as tiny calves Boc ⁇ /z// ⁇ microplus ), Haemaphysalis longicornis, Hyalomma anatolicum,
  • the compound of the invention has special effects especially for sucking and sucking mouthparts pests such as aphids, leafhoppers, planthoppers, thrips, whiteflies and the like.
  • Insecticide composition containing the active substance of the present invention containing the active substance of the present invention
  • the active substance of the present invention can be prepared into a pesticide composition in a conventional manner.
  • These active compounds can be formulated into conventional preparations such as solutions, emulsions, suspensions, powders, foams, pastes, granules; aerosols, natural and synthetic materials impregnated with active substances, Microcapsules in polymers, coatings for seeds, and preparations for use with combustion devices, such as smoked cartridges, smoked cans and smokers, as well as ULV cold mist and hot fog ( Warm mist) formulation.
  • preparations can be produced by known methods, for example, by mixing the active compound with an extender, which is a liquid or liquefied gas or solid diluent or carrier, and optionally a surfactant Emulsifiers and/or dispersants and/or bubble formers.
  • an extender which is a liquid or liquefied gas or solid diluent or carrier
  • a surfactant Emulsifiers and/or dispersants and/or bubble formers for example, when water is used as an extender, an organic solvent can also be used as an auxiliary.
  • a liquid solvent When a liquid solvent is used as the diluent or carrier, it is basically suitable, such as: aromatic hydrocarbons such as xylene, toluene or alkylnaphthalene; chlorinated aromatic or chlorinated aliphatic hydrocarbons such as chlorobenzene, vinyl chloride Or methylene chloride; aliphatic hydrocarbons such as cyclohexane or paraffin, such as mineral oil; alcohols such as ethanol or ethylene glycol and their ethers and lipids; ketones such as acetone, methyl ethyl ketone, methyl Butyl ketone or cyclohexanone; or less common polar solvents such as dimethylformamide and dimethyl sulfoxide, and water.
  • aromatic hydrocarbons such as xylene, toluene or alkylnaphthalene
  • chlorinated aromatic or chlorinated aliphatic hydrocarbons such as chlorobenzene, vinyl chloride Or methylene
  • a diluent or carrier for liquefied gas it is meant a liquid which will become a gas at normal temperature and pressure, such as an aerosol propellant such as a halogenated hydrocarbon and butane, propane, nitrogen and carbon dioxide.
  • an aerosol propellant such as a halogenated hydrocarbon and butane, propane, nitrogen and carbon dioxide.
  • Solid supports can be used on the ground for natural minerals such as kaolin, clay, talc, quartz, activated clay, montmorillonite, or diatomaceous earth, and ground synthetic minerals such as highly dispersed silicic acid, alumina and silicates.
  • the solid carrier for the granules is a ground and graded natural stone, such as calcite, marble, pumice, sepiolite and dolomite, as well as inorganic and organic coarse powder granules, and organic materials such as sawdust, coconut shell, Corn cobs and granules of tobacco stems.
  • a nonionic and anionic emulsified column can be used as the emulsifier and I or the foam forming agent.
  • polyoxyethylene-fatty acid esters polyoxyethylene-fatty alcohol ethers, such as alkylaryl polyglycol ethers, alkyl sulfonates, alkyl sulfates, aryl sulfonates, and white Protein hydrolysate.
  • Dispersing agents include, for example, lignin sulphite waste liquid and methyl cellulose.
  • Binders such as carboxymethylcellulose and natural and synthetic polymers in the form of powders, granules or emulsions such as gum arabic, polyvinyl alcohol and polyvinyl acetate may be used in the formulation.
  • Colorants such as inorganic dyes such as iron oxide, oxidized diamonds and Prussian blue; organic dyes such as organic dyes such as azo dyes or metal phthalocyanine dyes; and trace nutrients such as iron, lanthanum, boron, copper may be used. , cobalt, aluminum and zinc salts, etc.
  • the active compounds of the present invention may be formulated as a mixture with other active compounds in their commercial preparations or in the dosage forms prepared from these preparations.
  • These other active compounds are insecticides, baits, fungicides, killing agents. Tinctures, nematicides, fungicides, growth control agents, etc.
  • Insecticides include, for example, phosphates, carbamates, pyrethrins, chlorinated hydrocarbons, benzoylureas, nematotoxins, and substances produced by microorganisms such as avermectin.
  • the active compounds of the present invention may also be formulated as a mixture with synergists in their commercial preparations in the dosage form prepared from these preparations.
  • synergists are compounds which increase the action of the active compound. Since the active compound itself is active, it is not necessary to add a synergist.
  • formulations usually contain from 0.001 to 99.99% by weight, preferably from 0.01 to 99.9% by weight, more preferably from 0.05 to 90% by weight, of the active compound of the invention, of the insecticidal composition.
  • concentration of the active compound can vary over a wide range.
  • concentration of active compound in the dosage form used may range from 0.0000001 to 100% (g/v), preferably between 0.0001 and 1%.
  • Aromatic aldehyde (4.5 mmol, 1 50 mol %) was dissolved in absolute ethanol (30 mL) at room temperature, then malononitrile (4.5 mmol, 1 50 mol %) was added and stirring was continued, and piperidine was added dropwise. After stirring for 10 to 4 hours, the nitromethylene compound (3 mmol, 150 mol%) was added and the mixture was heated to reflux for 3 to 24 hours, cooled, filtered, and washed twice with dichloromethane to give a solid compound.
  • Example 10 A yellow solid was obtained after filtration, yield: 79%, m.p. 3 ⁇ 4 NMR
  • Example 12 A yellow solid was obtained after filtration, yield 65%, m.p.: 2521.
  • Example 19 A yellow solid was obtained after filtration, yield 10%, m.p.: 217.1-217.3.
  • Aphids belong to Homoptera pests and have a sucking mouthparts, which is a common crop pest.
  • the soybean meal cracc/rara was used as the test object and tested by the dipping method.
  • Operation process Accurately weigh various samples, add ⁇ , ⁇ -dimethylformamide to make 10g/L mother liquor, and dilute it to a concentration of 500 ug/mL with 0.2mL/LTntonX-100 aqueous solution. . Wait After being stably sucked on the bean sprouts, the wingless mites are immersed in the medicinal solution with a concentration of 500 ug/mL together with the bean sprouts, and taken out after 5 s. The excess liquid is sucked up with absorbent paper, and transferred to a clean vessel and kept at a constant temperature of 23 °C. Three replicates per concentration were used and the control group was an aqueous solution containing 0.2 mL/L Triton X-100. After 24 hours of treatment, the number of dead insects tested was counted and the mortality (%;) was calculated.
  • Mortality (%) (control live number - number of live insects) / number of live insects X 100%
  • the following components were prepared in proportion: 25% (by weight, the same below) of any of the compounds 1 - 71; 5% polyoxyethylene sorbitol hexaoleate; 70% higher aliphatic hydrocarbon oil.
  • the components were ground together in a sand mill until the solid particles fell below about 5 microns.
  • the resulting viscous suspension can be used as it is, but it can also be used after emulsification in water.
  • the following components were prepared in proportion: 25% of compound 1 -71 of any compound; 3% hydrated attapulgit; 10% calcium lignosulfonate; 0.5% sodium dihydrogen phosphate; 61.5% water.
  • the components are ground together in a ball mill until the solid particles fall below about 10 microns. This aqueous suspension can be used directly.

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Abstract

本发明涉及具有通式(A)的化合物或者该化合物的光学异构体、顺反异构体或农药学上可接受的盐, 及其制备方法。 本发明还涉及包含上述化合物、 或者其光学异构体、顺反异构体或农药学上可接受的盐的农用组合物,所述农用组合物的用途。 5 所述化合物及其衍生物对同翅目、鳞翅目等农林业害虫,例如蚜虫、飞虱、粉虱、叶蝉、蓟马、棉铃虫、菜青虫、小菜蛾、斜纹夜蛾、粘虫等具有高的杀虫活性。

Description

具有杀虫活性的含氮杂环化合物、 其制备及用途
技术领域
本发明涉及一种类新烟碱类的新型杀虫剂、 及其制备方法和应用。 技术背景
20世纪 80年代中期拜耳公司 (Bayer)开发出第一个新烟碱类杀虫剂吡虫啉,成 为最成功的新型杀虫剂之一, 以吡虫啉为代表的新烟碱类杀虫剂因杀虫活性高, 杀虫谱广, 对哺乳动物和水生动物毒性低, 且有良好的系统物性及适当的田间稳 定性和环境友好性, 成为新农药创制的重要热点领域。 后来又相继开发出噻虫啉、 噻虫胺、 噻虫嗪、 啶虫脒、 烯啶虫胺、 呋虫胺等一系列烟碱类杀虫剂 (欧洲专利 247477 , 296453、 685477、 235725 , 235725 , 315826、 192060、 244777 , 0386565、 580553、 和 103 1566, 日本专利 62292765、 8259568、 8291 171、 和 7242633)。
但是由于吡虫啉过量频繁使用造成的较为严重的抗性问题以及由于结构相似 性带来的新烟碱杀虫剂之间的交互抗性, 在一定程度上限制了该类化合物的应用, 成为制约此类化合物发展的重要问题, 同时新烟碱类杀虫剂主要对同翅目和鞘翅 目害虫高效, 其相对较窄的杀虫谱也限制了虫害防治方面的用药选择性。
因此, 如何对具有高活性的硝基亚甲基化合物进行结构改造, 以产生新的、 更 有效的杀虫剂, 解决新烟碱类杀虫剂的抗性问题, 扩大杀虫谱, 使其应用于杀虫 剂就成为本发明需要解决的技术问题。 发明内容
本发明目的在于, 提供一类更高效的防治害虫的化合物及其制备方法。
本发明的另一个目的是为生长中的和收获的作物不受昆虫攻击和侵扰而提供 保护。 在本发明的第一方面, 提供了一种具有通式 (A)所示结构的化合物, 或所述化 合物的光学异构体、 顺反异构体或农药学上可接受的盐:
Figure imgf000002_0001
式中: !^为含氮、 氧和 /或硫的五元或六元杂环基, 卤代的含氮、 氧和 /或硫的五元或 六元杂环基, 或者取代或未取代的苯基, 其中, 所述取代基为选自下组中的一个 或多个 (如 1-3个;): 卤素, d— 4卤代烷基或 d— 4氯代烷氧基;
R2、 R3各自独立地为 H, d_6烷基, 烯丙基, 苄基, 带 2-4个 C的烷氧基烷基, 带 1-3个 C的烷氧基羰基, 苯氧羰基, 带 2-6个 C的炔基羰基, 带 2-3个 C的烯 基羰基, 带 3-6个 C的环烷基羰基, 苯甲酰基或取代的苯甲酰基, 呋喃羰基, 或 Ν,Ν-二甲基羰基, 或者 R2 禾卩 R3 共同构成 -CH2-CH2-或 -CH2-CH2-CH2-; -CH2-XR-CH2-, 其中 X为选自 N, 0或 S的杂原子, R是杂原子上的 d.6烷基或 烷氧基;
R4为 H, d_6烷基, 烯丙基, 烯基, 苄基, 含氮、 氧和 /或硫的五元或六元杂 环基, ¾代的含氮、 氧和 /或硫的五元或六元杂环基, 或取代或未取代的苯基;
R5和 R6各自独立地为 H, d_6烷基, 烯丙基, 苄基, 带 2-4个 C的烷氧基烷 基, 带 1 -3个 C的烷氧基羰基, 苯氧羰基, 带 2-6个 C的炔基羰基, 带 2-3个 C 的烯基羰基, 带 3-6个 C的环烷基羰基, 苯甲酰基或取代的苯甲酰基, 磺酰基, 含氮、 氧和 /或硫的五元或六元杂环羰基, ¾代的含氮、 氧和 /或硫的五元或六元杂 环羰基, 或 Ν,Ν-二甲基羰基, 或者 和 共同构成 -CH2-(CH2)n-CH2- (n = 0, 1, 2, 3, 或 4);
Y为硝基, 氰基, 三氟甲基, 三氟乙酰基, 或三氟甲磺酰基;
Z为硝基, 氰基, 酯基, 酰胺基, 甲羧基, 甲羟基, 或三氟甲基。
在一个优选的实施方式中, 选自: 吡啶基、 噻唑基、 嘧啶基、 四氢呋喃基、 噁唑基, 或其卤代物。
在一个优选例中, 为卤代的吡啶基、 卤代的噻唑基、 卤代的嘧啶基、 卤代 的四氢呋喃基、 或卤代的噁唑基, 更优选所述卤代物为氯代物。 在另一个优选例中, !^为
Figure imgf000003_0001
在另一个优选实施方式中, R2、 R3为氢或 Cw烷基, 或者 和 共同构成 -CH2-CH2-或 -CH2-CH2-CH2-, -CH2-XR-CH2-, 其中 X为 N, 0, S等杂原子, R是 杂原子上的 C1-6烷基或烷氧基。
在一个优选例中, R2、 R3为氢或 CM烷基, 优选氢、 甲基或乙基, 或者 和 R3共同构成 -CH2-CH2-或 -CH2-CH2-CH2-。
在另一个优选的实施方式中, R4为 H, d_6烷基, 取代或未取代的吡啶基、 噻 唑基、 嘧啶基、 四氢呋喃基、 噁唑基, 或取代或未取代的苯基。
在一个优选例中, 为甲基、 乙基、 或丙基, 或者 R4是不同取代的苯基。 在另一个优选的实施方式中, R5、 R6为氢, 磺酰基, 或羰基。 在一个优选例中, R5、 R6为氢。
在另一个优选的实施方式中, Y为硝基或氰基。
在一个优选例中, Y为硝基。
在另一个优选的实施方式中, Z为硝基, 氰基, 酯基, 或三氟甲基。
在一个优选例中, Y为氰基, 三氟甲基或者酯基。
在本发明的第二方面, 提供了一种农用组合物, 其包含:
(a) 0.001 -99.99重量%的本发明第一方面中所述的化合物、 其光学异构体、 顺 反异构体或农药学上可接受的盐、 或者它们的组合; 以及
(b) 农药学上可接受的载体和 /或赋形剂。
在一个优选例中, 组分 (a)占所述农用组合物的 0.01 -99.9重量%, 优选 0.05-90 重量%。
在一个优选的实施方式中,所述农用组合物用于杀灭或预防选自下组的害虫: 鞘翅目、 鳞翅目、 半翅目、 直翅目、 等翅目或双翅目昆虫。
在一个优选例中, 所述害虫具有刺吸式或锉吸式口器。
在另一优选例中, 所述害虫为蚜虫、 飞虱、 粉虱、 叶蝉、 蓟马、 棉铃虫、 菜 青虫、 小菜蛾、 斜紋夜蛾、 或粘虫。
在另一优选例中,所述农用组合物还包含其它活性物质,所述其它活性物质选 自: 杀虫剂、 饵剂、 杀菌剂、 杀螨剂、 杀线虫剂、 杀真菌剂或生长控制剂。
在本发明的第三方面, 本提供本发明上述农用组合物的用途, 用于杀灭或预 防农业害虫、 卫生害虫和危害动物健康的害虫; 或用作用于杀灭或预防农业害虫、 卫生害虫和危害动物健康的杀虫剂组合物。
在本发明的第四方面, 提供了一种杀虫和 /或防虫方法, 所述方法包括将上述 农用组合物施加于遭受或可能遭受虫害的植物体、 其周围的土壤或环境中。
在本发明的第五方面, 提供了本发明上述化合物、 其光学异构体、 顺反异构 体或农药学上可接受的盐、 或它们的组合在制备杀虫剂组合物中的用途。
在本发明的第六方面, 提供了本发明上述化合物、 其光学异构体、顺反异构体 或农药学上可接受的盐的制备方法, 所述方法包括, 在催化剂存在时使式 I 的化 合物、式 II的化合物和式 III的化合物在一定反应温度下在反应溶剂中反应一定时 间, 从而得到式 A的化合物:
Figure imgf000004_0001
式中, R2、 R3、 R4、 Y和 Z如上文中所定义。
在另一优选例中, 所述反应溶剂为水, 乙醇, 甲醇, 乙腈, 二甲基亚砜, Ν,Ν- 二甲基甲酰胺, 甲酸, 乙酸。
在另一优选例中, 所述反应溶剂选自乙腈或乙醇, 优选乙醇。
在另一优选例中, 所述反应温度为 0-200 °C。
在另一优选例中, 所述反应时间为 3-24小时。
在另一优选例中, 所述催化剂是脯氨酸或脯氨酸衍生物, 哌啶, DBU, DMAP, 三乙胺, 二异丙基乙胺, 吡啶或者含有取代基的吡啶, 盐酸, 甲酸, 乙酸, 三氟 化硼, 三氯化铝, 三氯化铁。
在另一优选例中, 所述催化剂选自浓盐酸、 脯氨酸或哌啶, 优选哌啶。
在一个优选的实施方式中, 所述方法包括步骤: 在乙醇溶液中使用 10%的哌 啶, 于回流条件下, 进行如下反应 3-24小时, 然后在有机碱条件下进行烷基化从 而获得通式 A的化合物:
Figure imgf000005_0001
在本发明的第七方面, 提供了制备本发明第二方面所述农用组合物的方法, 包括步骤: 将 (a)本发明第一方面中所述的化合物、 其光学异构体、 顺反异构体或 农药学上可接受的盐、 或者它们的组合; 与 (b) 农药学上可接受的载体和 /或赋形 剂进行混合, 从而形成农用组合物。 具体实施方式
本发明人通过长期而深入的研究, 在现有的硝基亚甲基类新烟碱杀虫剂的结 构基础之上保留了活性药效团硝基亚甲基, 引入了 1,4-二氢吡啶结构, 对新烟碱 类杀虫剂结构进行了骨架的改变, 从而意外地首次合成了一类新型的类新烟碱化 合物, 该化合物的杀虫活性显著提高, 并具有扩大的杀虫谱。 在此基础上, 发明 人完成了本发明。 基团定义
如本文所用, 术语 " 烃基" 是指具有 1 -6个碳原子的烷基、 烯基、 炔基、 环烷基、 环烯基、 芳基等仅含碳、 氢的饱和或不饱和基团, 优选烷基、 烯基或炔 基。 术语 "烯基" 指具有 2-6 个碳原子的直链或支链的烯基, 例如乙烯基、 烯丙 基、 1 -丙烯基、 异丙烯基、 1 -丁烯基、 2-丁烯基、 或类似基团。
术语 "炔基" 是指具有 2-6 个碳原子的直链或支链的炔基, 例如乙炔基、 丙 炔基等。
术语 "环烷基" 指环丙基、 环丁基、 环戊基、 环己基、 或环庚基等。
如本文所用, 术语 " 烷基"指具有 1 -6个碳原子的直链或支链烷基, 例如 甲基、 乙基、 丙基、 异丙基、 丁基、 异丁基、 仲丁基、 叔丁基、 或类似基团。
术语 " C^烷氧基" 指具有 1 -6个碳原子的直链或支链烷氧基, 例如甲氧基、 乙氧基、 丙氧基、 异丙氧基、 丁氧基、 异丁氧基、 仲丁氧基、 叔丁氧基、 或类似 基团。
术语 "卤素" 指氟、 氯、 溴、 或碘。 术语 "卤代的" 指被相同或不同的一个 或多个上述卤原子取代的基团, 例如三氟甲基、 五氟乙基、 或类似基团。
术语 " c5_12芳基"指单环至三环的芳族烃基, 例如苯基、 萘基、 或类似基团。 术语 "芳烷基" 指被上述芳基取代的 烷基。
术语 "五元或六元杂环基" 指含一个或多个选自氮、 氧或硫的杂原子的五元 或六元环, 例如吡啶基、 噻唑基、 嘧啶基、 四氢呋喃基、 或噁唑基等。 本发明活性物质的杀虫活性
术语 "本发明的活性物质" 或 "本发明的活性化合物" 是指本发明化合物、 其光学异构体、 顺反异构体或农药学上可接受的盐, 其具有 1 ,4-二氢吡啶结构, 其具有显著的杀虫活性, 以及扩大的杀虫谱。
术语 "农药学上可接受的盐" 意指该盐的阴离子在形成杀虫剂药学上可接受 的盐时为已了解的和可接受的。 该盐较好的为水溶性的。 合适的, 由式 (A)的化合 物形成的酸加成盐包括有无机酸形成的盐, 例如盐酸盐、 磷酸盐、 硫酸盐、 硝酸 盐; 及包括有机酸形成的盐, 如醋酸盐, 苯甲酸盐。
本发明的活性物质能用作控制和消灭广泛的农林植物害虫、贮藏谷类的害虫、 以及公共卫生害虫等。 在本说明书中, "杀虫剂" 是具有防治上述提到的所有害 虫的作用的物质的统称。
害虫的例子包括但不限于: 鞘翅目昆虫, tw H iSUopM zeamais) , 赤拟 谷盜 (Tribolium castanetmi) , ^^ Wi^ ( enosepilachna vigintioctomaculata) , 二十 八星瓢虫 (Hewfwe zYac/ma sparsa) , 细胸叩头虫 ( gr/ot^ /^c/co/// , 红脚绿金龟 (Anomala cupripes) , 四紋 1313金龟 CPop〃a quadri guttata) , 马铃薯叶甲 (Mo"o/¾?ta hieroglyphic a) , ^h .^ (Monochamus alternatus) , ^ -(Echi oc emus squameus) , P† Ep [Basiprionota bisignata) ,星天牛 (Anoplophora chinensis) ,桑天牛 (Apripona germari) , 胼腹小蠹
Figure imgf000007_0001
/i«c/co〃/ ; 鳞翅目 昆虫, 如舞毒娥 tifopar), 夭幕毛 ikXMalacosoma neustria testacec), 黄杨 i¼ (Diaphania perspectalis) , 大袋蛾 (C7a"a variegata) , M ¾ {Cnidocampa flauescens) , ¾ j¾ ¾ ¾ i¾ {Dendrolimus punctatus) , 古毒蛾 (Orgy/a gonostigma), 白 l¾ ® ¾ (Paranthrene tabaniformis) , 斜紋夜蛾 (S ot/op tera litura) , 二化螺 (Czz7o suppressalis), 玉米螺 (Ostrinia nubilalis), 粉斑螺 (Ephestia cautella), 棉卷蛾 (Adoxophyes orana) , ¾ ^ ¾ ¾ (laspyresia splendana) ,小地老虎 (Agrotis fucosa),
Figure imgf000007_0002
xylostella) , tn ¾ ¾ (Phyllocnistis citrella), 或东方粘虫
Figure imgf000007_0003
c/wct/ce;w), IS¾ Ml {Nilaparvata lugens) , ^,Ψτϊ^ϊ (Pseudococcus corns tocki), 矢尖虫介 (f/wfl s yanonensis) , ^^S(M zus persicae), ^ !fej (A phis gossydii) , 萝卜虫牙 (Jpopz/s erj^/m/ pseudobrassicae) , ¾¾¾ 1*3
Figure imgf000007_0004
tabaci); 直翅目昆 虫, 如德国小蠊 C6/atfe〃<2 germaw/ca), 美国大蠊 ( ^rp/aweto amer/caw), 非洲蝼蛄 (Gryllotalpa africana), 或亚洲飞蝗 (Joc m/grator/α); 等翅目昆虫, 如入侵红火蚁 (Solenopsis invicta) , 或家白虫义 (Coptotermes formosanus); 双翅目昆虫, 如家虫黾 (Musca domestica) , ^k k.^ . Aedes aegypti), ^^(Delia platura), -^i{Culex sp.), 或中华按蚊 ½o;^e/^ sinensis); 危害动物健康的害虫, 如微小牛蜱 Boc^/z//^ microplus) , 长角血蜱 (Haemaphysalis longicornis) , 小亚璃目艮蜱 (Hyalomma anatolicum) , ^.^(Hpoderma spp.), 肝片吸 }i (Fascio!a hepatica), 贝氏莫尼茨 练^ (Moniezia blanchard) , ¾ ¾ΙτΨί ^ il(Ostertagia spp.) , Hi i¾ (Trypanosoma enansi, Babesia bigeminal等。
本发明涉及的化合物尤其对刺吸式、 锉吸式口器害虫如: 蚜虫、 叶蝉、 飞虱、 蓟马、 粉虱等农林害虫有特效。 含本发明活性物质的杀虫剂组合物
可将本发明的活性物质以常规的方法制备成杀虫剂组合物。 这些活性化合物 可做成常规的制剂, 例如溶液剂, 乳剂, 混悬剂, 粉剂, 泡沬剂, 糊剂, 颗粒剂; 气雾剂, 用活性物质浸渍的天然的和合成的材料, 在多聚物中的微胶囊, 用于种 子的包衣复方, 和与燃烧装置一块使用的制剂, 例如烟熏药筒, 烟熏罐和烟熏盘, 以及 ULV冷雾 (Cold mist)和热雾 (Warm mist)制剂。
这些制剂可用已知的方法生产, 例如, 将活性化合物与扩充剂混合, 这些扩 充剂就是液体的或液化气的或固体的稀释剂或载体, 并可任意选用表面活性剂即 乳化剂和 /或分散剂和 /或泡沬形成剂。 例如在用水作扩充剂时, 有机溶剂也可 用作助剂。
用液体溶剂作稀释剂或载体时, 基本上是合适的, 如: 芳香烃类, 例如二甲 苯, 甲苯或烷基萘; 氯化的芳香或氯化的脂肪烃类, 例如氯苯, 氯乙烯或二氯甲 烷; 脂肪烃类, 例如环己烷或石蜡, 例如矿物油熘分; 醇类, 例如乙醇或乙二醇 以及它们的醚和脂类; 酮类, 例如丙酮, 甲乙酮, 甲基异丁基酮或环已酮; 或不 常用的极性溶剂, 例如二甲基甲酰胺和二甲基亚砜, 以及水。
就液化气的稀释剂或载体说, 指的是在常温常压下将成为气体的液体, 例如 气溶胶推进剂, 如卤化的烃类以及丁烷, 丙烷, 氮气和二氧化碳。
固体载体可用地面天然的矿物质, 例如高岭土, 粘土, 滑石, 石英, 活性白 土, 蒙脱土, 或硅藻土, 和地面合成的矿物质, 例如高度分散的硅酸, 氧化铝和 硅酸盐。 供颗粒用的固体载体是碾碎的和分级的天然告石, 例如方解石, 大理石, 浮石, 海泡石和白云石, 以及无机和有机粗粉合成的颗粒, 和有机材料例如锯木 屑, 椰子壳, 玉米棒子和烟草梗的颗粒等。
非离子的和阴离子的乳化列可用作乳化剂和 I或泡沬形成剂。 例如聚氧乙烯- 脂肪酸酯类, 聚氧乙烯-脂肪醇醚类, 例如烷芳基聚乙二醇醚类, 烷基磺酸酯类, 烷基硫酸酯类, 芳基磺酸酯类以及白蛋白水解产物。 分散剂包括, 例如木质素亚 硫酸盐废液和甲基纤维素。
在制剂中可以用粘合剂, 例如羧甲基纤维素和以粉末, 颗粒或乳液形式的天 然和合成的多聚物, 例如阿拉伯胶, 聚乙烯基醇和聚乙烯醋酸酯。
可以用着色剂例如无机染料, 如氧化铁, 氧化钻和普鲁士蓝; 有机染料, 如 有机染料, 如偶氯染料或金属钛菁染料; 和用痕量营养剂, 如铁, 猛, 硼, 铜, 钴, 铝和锌的盐等。
本发明的这些活性化合物可与其他活性化合物制成一种混合物存在于它们的 商品制剂中或从这些制剂制备的使用剂型中, 这些其他的活性化合物为杀虫剂, 合饵, 杀菌剂, 杀螨剂, 杀线虫剂, 杀真菌剂, 生长控制剂等。 杀虫剂包括, 例 如磷酸酯类, 氨基甲酸酯类, 除虫菊酯类, 氯化烃类, 苯甲酰脲类, 沙蚕毒素类 以及由微生物产生的物质, 如阿维菌素。
此外, 本发明的这些活性化合物也可与增效剂制成一种混合物存在于它们的 商品制剂中成从这些制剂制备的使用剂型中。 增效剂是提高活性化合物作用的化 合物, 由于活性化合物本身有活性, 也可不必加增效剂。
这些制剂通常含有占所述杀虫剂组合物 0.001 -99.99重量%,优选 0.01 -99.9重 量%, 更优选 0.05-90重量%的本发明的活性化合物。 从商品制剂制成使用剂型中 的活性化合物的浓度可在广阔的范围内变动。 使用剂型中的活性化合物的浓度可 从 0.0000001 - 100%(g/v), 最好在 0.0001与 1 %之间。 本发明化合物的制备方法
通式 (A)化合物的合成方法如下:
Figure imgf000009_0001
EtOH, 回流
Re
Figure imgf000009_0002
实施例
下面结合具体实施例, 进一步阐述本发明。 应理解, 这些实施例仅用于说明 本发明而不用于限制本发明的范围。 下列实施例中未注明具体条件的实验方法, 通常按照常规条件, 或按照制造厂商所建议的条件。 除非另外说明, 否则百分比 和份数按重量计算。 实施例 1-22 : 1,4-二氢吡啶类硝基亚甲基化合物的制备
Figure imgf000009_0003
在室温条件下将芳香醛 (4.5 mmol , 1 50 mol %)溶解在无水乙醇 (30 mL)溶液中, 然后加入丙二腈 (4.5 mmol , 1 50 mol %)继续搅拌, 滴加哌啶(10 mol %)后搅拌 2-4 小时, 然后加入硝基亚甲基化合物 (3 mmol , 150 mol %)升温回流 3-24小时, 冷却 后过滤, 二氯甲烷洗涤 3次, 得到固体化合物。
Figure imgf000010_0001
实施例 1
实施例 1: 过滤后得到黄色固体, 产率为 82%, 熔点: 223.2-223.7°C。 NMR (400 MHz, DMSO-d6) ^3.93-4.01 (m, 3H), 4.08-4.17 (m, 1H), 4.72 (s, 1H), 4.74 (s, 2H), 6.54 (s, 2H, NH2), 6.98 (dd, J= 1.4, 7.8 Hz, 1H), 7.15-7.23 (m, 3H), 7.28 (d, J = 8.0 Hz, 1H), 7.64 (dd, J = 2.6, 8.2 Hz, 1H), 8.28 (d, J = 2.0 Hz, 1H)。 13CNMR (100 MHz, DMSO-d6) ^41.52, 43.90, 51.05, 51.46, 60.12, 106.17, 121.21, 124.39, 126.69, 126.96, 128.73, 131.40, 139.48, 144.78, 149.51, 149.61, 149.90, 152.90。 MS (ESI) m/z 409 (M + H)0 C2。H17C1N602计算值: C, 58.75; H, 4.19; N, 20.56。 实测值: C, 58.77; H, 3.89; N, 20.40。
Figure imgf000010_0002
实施例 2
实施例 2: 过滤后得到黄色固体, 产率为 78%, 熔点: 253.5-253.9°C。 NMR (400 MHz, DMSO-d6) ^4.02-4.15 (m, 4H), 4.70 (d, J= 15.6 Hz, 1H), 4.77 (d, J= 16.0 Hz, 1H), 4.81 (s, 1H), 6.70 (s, 2H, NH2), 7.21 (d, J= 8.0 Hz, 1H), 7.22 (d, J= 8.8 Hz, 2H), 7.60 (dd, J = 1.6, 8.0 Hz, 1H), 8.05 (d, J= 8.4 Hz, 2H), 8.17 (s, 1H)。 13CNMR(100MHz, DMSO-d6) ^41.58, 43.91, 51.34, 51.85, 58.47, 105.60, 120.83, 124.02, 124.26, 128.11, 131.28, 139.45, 146.58, 149.46, 149.93, 150.04, 152.08, 152.16。 MS (ESI) m/z 454 (M + H)。 C2。H16C1N704计算 值: C, 52.93; H, 3.55; N, 21.60。 实测值: C, 52.90; H, 3.39; N, 21.48。
Figure imgf000010_0003
实施例 3
实施例 3: 过滤后得到黄色固体, 产率为 59%, 熔点: 244.3-245.1°C。 NMR (400 MHz, DMSO-d6) 54.01-4.15 (m, 4H), 4.69 (d, J= 16.0 Hz, 1H), 4.74 (d, J= 16.0 Hz, 1H), 4.87 (s, 1H), 6.73 (s, 2H, NH2), 7.17 (d, J= 8.4 Hz, 1H), 7.44 (d, J = 7.6 Hz, 1H), 7.51 (t, J = 7.8 Hz, 1H), 7.60 (dd, J = 2.4, 8.4 Hz, 1H), 7.88 (t, J= 1.8 Hz, 1H), 8.07 (dd, J= 1.2, 8.0 Hz, 1H), 8.17 (d, J = 2.4Hz, 1H)。 13CNMR (100 MHz, DMSO-d6) δ 41.30, 43.96, 51.42, 51.53, 58.45, 105.83, 120.88, 121.39, 122.20, 124.14, 130.38, 131.18, 133.72, 139.37, 146.87, 148.07, 149.45, 149.81, 150.17, 152.32。 MS (ESI) m/z 454 (M + H)0 C20H16ClN7O4计算 值: C, 52.93; H, 3.55; N, 21.60。 实测值: C, 52.82; H, 3.22; N, 21.38。
Figure imgf000011_0001
实施例 4
实施例 4: 过滤后得到黄色固体, 产率为 41%, 熔点: 224.6-245.8 °C。 NMR (400 MHz, DMSO-d6) 4.00-4.13 (m, 4H), 4.68-4.77 (m, 3H), 6.67 (s, 2H, NH2), 7.16 (d, J = 8.4 Hz, 1H), 7.24 (d, J = 8.0 Hz, 2H), 7.63 (dd, J =2.4, 8.2 Hz, 1H), 7.64 (d, J= 8.4 Hz, 2H), 8.18 (s, 1H)。 13CNMR(100 MHz, DMSO-d6) 41.80, 43.89, 51.39, 51.70, 58.62, 105.66, 109.86, 119.36, 120.88, 124.30, 127.90, 131.27, 132.72, 139.42, 149.45, 149.92, 149.93, 150.10, 152.26。 MS (ESI) m/z 456 (M + Na)o C2。H16C1N702计算值: C, 58.14; H, 3.72; N, 22.60。 实测值: C, 58.00; H, 3.50; N, 22.49。
Figure imgf000011_0002
实施例 5
实施例 5: 过滤后得到黄色固体, 产率为 65%, 熔点: 246.4-247.5°C。 NMR (400 MHz, DMSO-d6) ^3.99-4.14 (rn, 4H), 4.73 (s, 2H), 4.78 (s, 1H), 6.65 (s, 2H, NH2), 7.24 (d, J= 8.0 Hz, 1H), 7.36 (d, J=7.2Hz, 1H), 7.43 (t, J=7.2Hz, 1H), 7.50 (s, 1H), 7.62 (s, 2H), 8.22 (s, 1H)。 13CNMR(100 MHz, DMSO-d6) δ 41.55, 43.92, 51.48, 51.57, 58.90, 105.74, 111.76, 119.38, 120.91, 124.21, 129.94, 130.51, 131.02, 131.26, 132.15, 139.39, 146.35, 149.48, 149.82, 149.90, 152.42。 HRMS (ESI) C21H16C1N702 +Na 计算值: 456.0952; 实测值: 456.0970。
Figure imgf000012_0001
实施例 6
实施例 6: 过滤后得到黄色固体, 产率为 61%, 熔点: 191.5-192.0°C。 NMR (400 MHz, DMSO-d6) ^3.97-4.16 (m, 4H), 4.74 (s, 3H), 6.60 (s, 2H, NH2), 7.10 (d, J= 8.8 Hz, 2H), 7.18 (d, J= 8.0 Hz, 2H), 7.28 (d, J= 8.4 Hz, 1H), 7.65 (dd, J=2.6, 8.2 Hz, 1H), 8.26 (d, J=2.0Hz, 1H)。 13C NMR (100 MHz, DMSO-d6) δ 41.13, 43.89, 51.36, 51.50, 59.46, 105.92, 119.29, 121.06, 121.20, 121.84, 124.28, 128.62, 131.40, 139.47, 144.14, 147.40, 149.59, 149.67, 149.90, 152.58。 MS (ESI) m/z 515 (M +Na)。 HRMS (ESI) C21H16C1F3N603 + Na 计算值 515.0822; 实测值 515.0832ο
Figure imgf000012_0002
实施例 7
实施例 7: 过滤后得到黄色固体, 产率为 64%, 熔点: 237.7-238.2°C。 NMR (400 MHz, DMSO-d6) ^3.91-4.15 (m, 4H), 4.73 (s, 3H), 6.62 (s, 2H, NH2), 6.97 (d, J =1.6 Hz, 1H), 7.17 (t, J= 7.8 Hz, 1H), 7.26 (t, J= 1.8 Hz, 1H), 7.28 (d, J= 8.0 Hz, 1H), 7.37-7.39 (m, 1H), 7.65 (dd, J= 2.4, 8.4 Hz, 1H), 8.25, (d, J =2.0 Hz, 1H)。 13C NMR (100 MHz, DMSO-d6) ^41.40, 43.92, 51.12, 51.53, 59.17, 105.81, 121.02, 122.05, 124.31, 125.96, 129.59, 129.98, 131.00, 131.28, 139.37, 147.52, 149.53, 149.79, 149.88, 152.67。 MS (; ESI) m/z 509 ( 1 + Na)。 C2。H16BrClN602计算值: C, 49.25; H, 3.31; N, 17.23。 实测值: C, 49.19; H, 3.01; N, 17.05。
Figure imgf000012_0003
实施例 8
实施例 8:过滤后得到黄色固体,产率为 60%,熔点: 123.7°C (分解)。 1HNMR (400 MHz, DMSO-t/6) ^4.01 (m, 3H), 4.10 (m, 1H), 4.73 (s, 1H), 4.76 (s, 1H), 5.74 (s, 1H), 6.65 (s, 2H, NH2), 7.09 (dd, J = 2.0, 8.4 Hz, 1H), 7.28 (d, J= 8.0 Hz, 1H), 7.32 (d, J=2.0Hz, 1H), 7.39 (dd, J= 1.2, 8.4 Hz, 1H), 7.69 (dd, J = 2.4, 8.0 Hz, 1H), 8.24 (d, J = 2.4 Hz, 1H)。 13C NMR (100 MHz, OMSO-d6) 31.11, 41.19, 43.91, 51.44, 51.59, 58.76, 105.53, 119.26, 120.89, 121.82, 123.32, 124.15, 126.16, 127.51, 129.21, 131.28, 139.39, 143.07, 146.07, 149.51, 149.91, 152.39。 HRMS (ESI) C21H15C12F3N603 + Na 计算值 549.0432; 实测值 549.0453。
Figure imgf000013_0001
实施例 9
实施例 9: 过滤后得到黄色固体, 产率为 22%, 熔点: 247.9-250.0°C。 NMR
(400 MHz, OMSO-d6) S4.07 (m, 4H), 4.75 (s, 2H), 5.03 (s, 1H), 6.54 (s, 2H, NH2), 7.04 (d, J =6.0 Hz, 1H), 7.44 (t, J =8.0 Hz, 2H), 7.62 (d, J= 1.6 Hz, 1H), 7.79 (dd, J =2.4, 8.0 Hz, 1H), 8.30 (d, J= 1.6 Hz, 1H)。 13C NMR (100 MHz, OMSO-d6) S31.93, 43.91, 51.69, 51.78, 60.32, 106.71, 120.09, 122.48, 124.50, 125.52, 125.58, 131.52, 131.86, 132.23, 133.23, 139.78, 144.38, 149.65, 149.71, 150.07, 152.26。 HRMS (ESI) C21H15C12F3N602 + H 计算值 511.0664; 实测值 511.0677。
Figure imgf000013_0002
实施例 10
实施例 10:过滤后得到黄色固体,产率为 79%,熔点: 233.5-233.8°C。 ¾ NMR
(400 MHz, DMSO-t/6) ^3.95-4.06 (m, 3H), 4.13-4.16 (m, 1H), 4.75 (s, 2H), 4.93 (s, 1H), 6.57 (s, 2H, NH2), 6.81 (t, J= 6.8 Hz, 1H), 7.02 (m, 1H), 7.24 (m, 1H), 7.34 (d, J=8.4Hz, 1H), 7.73 (dd, J=2.4, 8.4 Hz, 1H), 8.26 (d, J=2.4Hz, 1H)。 13C NMR (100 MHz, DMSO-t/6) ^37.28, 43.97, 51.33, 51.55, 58.96, 104.88, 115.89, 116.06, 120.57, 124.31, 124.91, 131.24, 134.19, 134.29, 139.65, 146.63, 146.76, 148.73, 148.87, 149.21, 149.51, 149.57, 149.68, 149.98, 151.18, 151.30, 152.55。 HRMS (ESI) C2。H15C1F2N602 + Na 计算值 467.0811; 实测值 467.0807。
Figure imgf000014_0001
实施例 11
实施例 11: 过滤后得到黄色固体,产率为 49%, 熔点: 261.7-262.1°C。 ipiNMR (400 MHz, DMSO-d6) ^4.01-4.14 (m, 4H), 4.72 (d, J= 15.6 Hz, 1H), 4.78 (d, J= 16.0 Hz, 1H), 5.14 (s, 1H), 6.53 (s, 2H, NH2), 6.98 (d, J= 8.4 Hz, 1H), 7.20 (dd, J = 2.0, 8.0 Hz, 1H), 7.42 (d, J= 8.0 Hz, 1H), 7.46 (d, J = 2.0 Hz, 1H), 7.77 (dd, J = 2.2, 8.2 Hz, 1H), 8.31, (d, J= 1.6 Hz, 1H)。 13C NMR (100 MHz, DMSO-d6) ^39.67, 43.88, 51.31, 51.85, 59.12, 105.54, 120.39, 124.46, 127.89, 129.05, 131.42, 131.62, 132.12, 133.00, 139.79, 141.47, 149.49, 149.74, 150.03, 152.71。 MS (ESI) m/z All (M + H)0 C2。H15C13N602计算值: C, 50.28; H, 3.16; N, 17.59。 实测值: C, 50.36; H, 2.90; N, 17.38。
Figure imgf000014_0002
实施例 12
实施例 12:过滤后得到黄色固体,产率为 65%,熔点: 252.1-253.0°C。 NMR (400 MHz, DMSO-d6) ^3.96-4.18 (m, 4H), 4.77 (t, J= 17.0 Hz, 2H), 4.89 (s, 1H), 6.56 (s, 2H, NH2), 7.01 (t, J=8.2Hz, 1H), 7.09 (d, J= 8.0 Hz, 1H), 7.23 (d, J= 10.4 Hz, 1H), 7.36 (d, J= 8.0 Hz, 1H), 7.72 (d, J= 8.0 Hz, 1H), 8.26 (s, 1H)。 13CNMR (100 MHz, DMSO-d6) ^43.95, 51.44, 51.52, 56.51, 58.95, 104.94, 116.28, 116.54, 120.60, 124.39, 124.88, 124.91, 130.65, 130.78, 131.15, 131.20, 131.29, 132.29, 132.39, 139.64, 149.53, 149.68, 150.11, 152.46, 158.83, 160.31。 HRMS (ESI) C20H15Cl2FN6O2 + Na 计算值 483.0515; 实测值 483.0523。
Figure imgf000015_0001
实施例 13
实施例 13:过滤后得到黄色固体,产率为 72%,熔点: 265.4-265.8°C。 NMR (400 MHz, DMSO-d6) 3.98-4.05 (m, 3H), 4.09-4.12 (m, 1H), 4.71 (d, J= 15.6 Hz, 1H), 4.76 (d, J= 15.6 Hz, 1H), 5.12 (s, 1H), 6.53 (s, 2H, NH2), 6.89 (d, J= 8.4 Hz, 1H), 7.31 (dd, J = 2.0, 8.0 Hz, 1H), 7.42 (d, J= 8.0Hz, 1H), 7.56 (d, J = 2.0 Hz, 1H), 7.76 (dd, J=2.4, 8.4 Hz, 1H), 8.30 (d, J = 2.0 Hz, 1H)。 13C NMR (100 MHz, DMSO-d6) 40.10, 43.88, 51.33, 51.85, 59.01, 105.51, 120.25, 120.39, 124.48, 130.78, 131.43, 131.77, 131.92, 133.23, 139.80, 141.86, 149.49, 149.74, 150.04, 152.68。 HRMS (ESI) C20H15BrCl2N6O2 + Na 计算值 542.9715; 实测值 542.9741。
Figure imgf000015_0002
实施例 14
实施例 14:过滤后得到黄色固体,产率为 40%,熔点: 202.6-203.2°C。 NMR (400 MHz, DMSO-d6) ^2.23 (s, 3H), 3.90-4.01 (m, 3H), 4.14-4.20 (m, 1H), 4.73 (d, J= 16.0 Hz, 1H), 4.78 (d, J= 15.6Hz, 1H), 4.84 (s, 1H), 6.49 (s, 2H, NH2), 6.82 (dd, J =2.0, 7.6 Hz, 1H), 6.90 (dd, J= 8.6, 10.6 Hz, 1H), 6.99-7.02 (m, 1H), 7.35 (d, J=8.4Hz, 1H), 7.70 (dd, J =2.2, 8.2 Hz, 1H), 8.29 (d, J=2.4Hz, 1H)。 13C NMR (100 MHz, DMSO-d6) ^20.72, 37.57, 43.97, 50.77, 51.46, 59.68, 105.02, 115.47, 115.68, 120.74, 124.35, 129.21, 129.28, 130.03, 130.07, 130.99, 131.12, 131.27, 133.59, 133.62, 139.64, 149.33, 149.71, 149.90, 152.90, 157.47, 159.88。 MS (ESI) m/z441 (M + H)。 C21H18C1FN602计算值: C, 57.21; H, 4.12; N, 19.06。 实测值: C, 56.98; H, 3.78; N, 18.79。 HRMS (ESI) C21H18C1FN602 + H 计算值 441.1242; 实测值 441.1225。
Figure imgf000016_0001
实施例 15:过滤后得到黄色固体,产率为 63%,熔点: 236.2-236.9°C。 NMR (400 MHz, OMSO-d6) S2A\ (s, 3H), 3.96-4.14 (m, 4H), 4.75 (d, J= 16.0 Hz, 1H), 4.77 (d, J= 15.6 Hz, 1H), 4.99 (d, J= 2.0 Hz, 1H), 6.48 (s, 2H, NH2), 6.61 (dd, J=2.4, 10.0 Hz, 1H), 6.85-6.90 (m, 1H), 7.09-7.12 (m, 1H), 7.40 (d, J= 8.4 Hz, 1H), 7.83 (dd, J =2.4, 8.0 Hz, 1H), 8.31 (d, J = 2.0Hz, 1H)。 13CNMR (100 MHz, OMSO-d6) ^18.66, 38.25, 43.94, 51.09, 51.96, 60.55, 106.64, 113.44, 113.65, 113.81, 114.02, 120.89, 124.39, 130.69, 130.72, 131.47, 131.74, 131.82, 139.64, 146.54, 146.59, 148.95, 149.59, 149.92, 152.85, 160.39, 162.79。 HRMS (ESI) C21H18C1FN602 + Na 计算值 463.1061; 实测值 463.1056。
Figure imgf000016_0002
实施例 16
实施例 16:过滤后得到黄色固体,产率为 84%,熔点: 235.0-235.6°Co 1H雇 R (400 MHz, OMSO-d6) ^3.90-4.03 (m, 3H), 4.15-4.21 (m, 1H), 4.73 (s, 2H), 4.93 (s, 1H), 6.60 (s, 2H, NH2), 7.28 (d, J= 8.8 Hz, 1H), 7.32 (d, J= 8.4 Hz, 1H), 7.53 (dd, J = 2.0, 6.8 Hz, 1H), 7.67-7.70 (m, 2H), 8.25 (d, J=2.4Hz, 1H)。 13C NMR(100 MHz, OMSO-d6) S3S.69, 44.01, 50.96, 51.58, 58.34, 104.53, 117.36, 117.59, 120.53, 122.94, 124.26, 125.29, 125.58, 125.61, 125.65, 126.61, 126.65, 126.71, 126.75, 127.45, 127.49, 131.11, 132.55, 132.69, 139.54, 149.68, 149.78, 149.92, 152.58。 HRMS (ESI) C21H15C1F4N602 + Na 计算值 517.0779; 实测值 517.0786。
Figure imgf000016_0003
实施例 17
实施例 17:过滤后得到黄色固体 产率为 68%,熔点: 228.2-228.7°C。 HNMR (400 MHz, DMSO-t/6) ^4.02-4.12 (m, 4H), 4.74 (d, J=4.0Hz, 2H), 4.78 (s, 1H), 6.68 (s, 2H, NH2), 7.03 (d, J= 8.0 Hz, 1H), 7.10 (d, J= 11.6 Hz, 1H), 7.24 (d, J= 8.0 Hz, 1H), 7.59 (t, J= 8.0 Hz, 1H), 7.67 (dd, J= 2.4, 8.4 Hz, 1H), 8.21 (d, J=2.4Hz, 1H)。 13CNMR(100 MHz, OMSO-d6) δ Ι.62, 43.90, 51.52, 51.74, 58.36, 105.40, 115.23, 115.43, 120.79, 123.46, 123.49, 124.13, 127.61, 127.65, 131.23, 139.46, 149.51, 149.88, 150.04, 152.22, 152.89, 152.96。 HRMS (ESI) C21H15C1F4N602 + Na 计算值 517.0779; 实测值 517.0775。
Figure imgf000017_0001
实施例 18
实施例 18:过滤后得到黄色固体,产率为 32%,熔点: 257.4-258.4°C。 NMR (400 MHz, DMSO-d6) ^2.39 (s, 3H), 3.97-4.09 (m, 4H), 4.72 (d, J = 16.0 Hz, 1H), 4.76 (d, J= 16.8 Hz, 1H), 4.93 (d, J= 1.6 Hz, 1H), 6.51 (s, 2H, NH2), 6.75 (d, J = 9.6 Hz, 1H), 7.37 (d, J= 8.0 Hz, 1H), 7.41 (d, J = 7.2 Hz, 1H), 7.81 (dd, J =2.6, 8.2 Hz, 1H), 8.27 (d, J =2.0 Hz, 1H)。 13C NMR (100 MHz, DMSO-d6) ^18.26, 38.11, 43.91, 51.35, 51.96, 59.89, 105.53, 105.74, 106.42, 115.43, 115.65, 120.79, 124.33, 131.47, 132.94, 132.97, 134.28, 139.67, 146.40, 146.45, 149.00, 149.57, 149.96, 152.60, 156.35, 158.77。 MS (ESI) m/z 5\9(M + H)。 C21H17BrFN602计算值: C, 48.53; H, 3.30; N, 16.17。 实测值: C, 48.28; H, 2.98; N, 16.02。
Figure imgf000017_0002
实施例 19
实施例 19:过滤后得到黄色固体,产率为 10%,熔点: 217.1-217.3°C。 ¾ NMR (400 MHz, OMSO-d6) S3.73 (s, 3H), 3.89-4.41 (m, 4H), 4.49 (s, 1H), 4.66 (s, 1H), 4.75 (d, J= 2.4 Hz, 1H), 6.51 (s, 2H, NH2), 6.75-6.77 (m, 2H), 6.87 (s, 1H), 6.90 (s, 1H), 7.31 (d, J = 8.0 Hz, 1H), 7.65 (dd, J = 2.8, 8.0 Hz, 1H), 8.27 (d, J = 2.4 Hz, 1H)。 13C NMR (100 MHz, OMSO-d6) S 2.90, 43.89, 45.65, 48.44, 51.11, 51.37, 55.46, 60.46, 106.61, 114.08, 124.39, 124.79, 127.72, 131.45, 136.81, 139.49, 139.66, 149.38, 149.61, 149.
C21H19C1N603 + H 计算值 439.1285; 实测值 439.1274。
Figure imgf000018_0001
实施例 20
实施例 20: 过滤后得到黄色固体, 产率为 59%, 熔点: 180.1-180.9°C。 ipiNMR (400 MHz, OMSO-d6) S2A4 (s, 3H), 3.92-4.04 (m, 4H), 4.84 (d, J= 15.6 Hz, 1H), 4.94 (d, J= 15.6 Hz, 1H), 5.03 (s, 1H), 6.48 (s, 2H, NH2), 6.65 (d, J = 9.6 Hz, 1H), 6.86-6.90 (m, 1H), 7.10-7.14 (m, 1H), 7.59 (s, 1H)。 13CNMR(100 MHz, OMSO-d6) ^ 38.18, 43.92, 47.65, 50.27, 60.68, 106.96, 113.53, 113.74, 113.83, 114.04, 120.81, 130.78, 131.79, 131.86, 134.95, 142.16, 146.41, 146.46, 148.86, 152.03, 152.48, 160.46, 162.86。HRMS (ESI) C19H16C1FN602S + H 计算值 447.0806; 实测值 447.0793ο
Figure imgf000018_0002
实施例 21
实施例 21:过滤后得到黄色固体,产率为 88%,熔点: 247.7-248.2°C。 NMR (400 MHz, OMSO-d6) ^1.04 (t, J= 14.0 Hz, 3H), 3.91-3.99 (m, 2H), 4.08 (s, 1H), 4.11 (t, J= 8.1 Hz, 1H), 4.16-4.19 (m, 1H), 4.76 (q, 2H), 5.25(s, 1H), 7.16(d, J= 8.0 Hz, 1H), 7.42(m, 3H), 7.58(dd, J = 2.6, 8.4 Hz, 1H), 7.66(s, 2H, NH2), 7.85(s, 1H), 8.00 (d, J= 8.0 Hz, 1H), 8.17 (d, J =2.4 Hz, 1H)。 13C NMR(100 MHz, DMSO-d6) ^14.71, 43.39, 51.05, 79.20, 107.35, 121.45, 121.72, 124.14, 129.94, 131.20, 133.80, 139.35, 140.30, 147.69, 148.37, 149.47, 149.84, 150.82, 152.75, 167.83。 HRMS (ESI) C22H21C1N606 + K 计算值 539.0848; 实测 值 539.0839。
Figure imgf000019_0001
实施例 22
实施例 22:柱层析得到黄色固体,产率为 80%,熔点: 225.5-226.0°C。 ¾ NMR (400 MHz, DMSO-d6) ^2.05 (s, 3H), 4.20-4.45 (m, 4H), 4.79 (d, J= 15.6 Hz, 1H), 4.89 (d, J= 16.0Hz, 1H), 4.90 (s, 1H), 7.28 (d, J= 8.0 Hz, 1H), 7.32 (d, J= 8.8 Hz, 2H), 7.67 (dd, J= 1.6, 8.0 Hz, 1H), 8.25 (d, J=8.4Hz, 2H), 8.37 (s, 1H)。 13CNMR (100 MHz, DMSO-d6) ^20.16, 42.58, 44.91, 52.34, 52.85, 59.47, 106.60, 121.83, 125.02, 125.26, 129.11, 132.28, 140.45, 147.58, 150.46, 150.93, 151.04, 153.08, 153.16, 168.1。 MS (ESI) m/z 454 (M + H)。 HRMS (ESI) C22H18C1N705 + Na 计算值 518.0956; 实测值 518.0962。 实施例 23-24: 1,4-二氢吡啶类硝基亚甲基化合物的制备
Figure imgf000019_0002
:=CN, C〇〇C2H: 将 1.08 g(0.004 mol)N-((6-氯吡啶 -3-基)甲基) -N-乙基 -N-甲基 -2-硝基乙烯基
-1,1-二胺与 0.636 g(0.006mol)苯甲醛, 0.006 mol丙二腈或氰乙酸乙酯置于 50 ml 乙醇中, 加入催化量的哌啶, 加热至回流反应 10h, 反应结束将溶剂旋干, 得固体 产物。
Figure imgf000019_0003
实施例 23 实施例 23:柱层析得化合物 0.568g,产率 33.5%,熔点:215.5- 216.0°C。1HNMR (400 Mz, OMSO-d6): δ 8.45 (s, 0.38Η), 8.03 (s, 0.62H), 7.85 (d, J= 7.6 Hz, 0.37H), 7.53 (d, J =1.2 Hz, 0.45H), 7.09-7.34 (m, 4.71H), 6.81(s, 1.17H), 6.64 (s, 1.55H), 4.91(s, 0.31H), 4.75 (s, 0.54H), 4.41-4.81(m, 1.20H), 4.11 (d, J= 14.4 Hz, 0.55H), 3.26-3.32 (m, 1.25H), 3.15 (s, 0.96H), 3.11 (s, 1.92H), 2.97-3.05(m, 0.52H), 2.66-2.71(m, 0.37H), 1.19(s, 1.78H), 0.93(s, 1.21H)。 13C NMR (100 Mz, DMSO-t/6): δ 155.3, 155.1, 154.9, 153.8, 150.3, 150.2, 149.8143.6, 142.7, 140.6, 139.8, 131.5, 131.2, 129.2, 128.9, 127.3, 126.9, 126.2, 125.9, 124.6, 124.5, 120.5, 120.4, 117.9, 116.5,66.0, 65.4, 51.0, 50.6, 48.4, 46.3, 38.9, 38.0, 13.9, 13.7。 HRMS (ESI) C21H21C1N602 + Na 计算值 447.1313; 实测值 447.1311。
Figure imgf000020_0001
实施例 24
实施例 24:柱层析得到黄色固体,产率为 45%,熔点: 263.5-263.0°C。 NMR (400 Mz, DMSOO: δ 8.41 (s, 0.12H), 7.90 (s, 0.47H), 7.84 (d, J= 7.2 Hz, 0.11H), 7.66 (d, J= 8.0 Hz, 0.29H), 7.41-7.51 (m, 1.73H), 7.26 (dd, Jl =2.0 Hz, J2 = 8.0 Hz, 0.34H), 7.14 (d, J = 8.4 Hz, 0.06H), 6.94 (d, J =8.4 Hz, 0.35H), 6.67 (d, J= 8.8 Hz, 0.34H), 6.02 (s, 0.1 OH), 5.87 (s, 0.36H), 4.51 (s, 0.21H), 4.40 (d, J= 14.4 Hz, 0.38H), 4.25 (d, J= 14.8 Hz, 0.36H), 3.86-3.99 (m, 0.99H), 3.34-3.42 (m, 2.13H), 1.23 (t, Jl = 7.2 Hz, J2 = 14.4 Hz, 1.13H), 1.10 (t, Jl = 6.8 Hz, 0.36H), 1.04(t, Jl = 7.2 Hz, 1.21H), 0.83 (t, Jl = 6.8 Hz, 0.36H)。 HRMS (ESI) C24H25F3N504 + H 计算值 574.1236; 实测值 574.1213。 实施例 25: 本发明化合物的杀虫活性测试
(1): 对蚜虫的杀虫活性
蚜虫属于同翅目害虫,具有刺吸口器,是一种常见的农作物害虫。以豆蚜 cracc/rara)为测试对象, 采用浸渍法测试。
操作过程: 准确称量各种样品, 分别加入 Ν,Ν-二甲基甲酰胺配制成 10g/L母 液, 实验时用含 0.2mL/LTntonX-100的水溶液将其稀释至 500 ug/mL的浓度。 待 无翅成蚜在豆芽上稳定吸食后, 连同豆芽一起浸入浓度为 500 ug/mL的药液中, 5s后取出, 用吸水纸吸去多余药液, 移入干净器皿中于 23 °C恒温饲养。 每浓度设 3次重复, 对照组为含 0.2 mL/L Triton X-100的水溶液。 处理 24小时后, 统计试 蚜的死亡虫数, 并计算死亡率(%;)。
死亡率 (%) = (对照活虫数 -处理活虫数 )/对照活虫数 X 100%
(2): 对粘虫的杀虫活性
采用浸叶饲喂法。将新鲜的玉米叶片在上述溶液中浸渍 3秒,然后在室温下凉 干, 供试虫取食, 24h后检查并计算试虫的死亡率(%)(公式同上), 每处理使用 10 试虫, 设 3次重复。 以清水处理作空白对照。
Figure imgf000021_0001
Figure imgf000022_0001
TCl9.0/600ZN3/X3d 09.S.0/0T0Z OAV
Figure imgf000023_0001
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9t ΐ9 JSD JSD H 89
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it 0L JSD JSD H 09
\ς 06 JSD JSD H 69
9t £8 JSD JSD H 85
6t 68 JSD JSD H O I
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NzO
TCl9 .0/600ZN3/X3d 09 .S .0/0T0Z OAV 70 共同组成 H N02 C02Et 61 38
-CH2-CH2-
71 共同组成 NC— <^~^> ~ H N02 C02Et 72 47
-CH2-CH2- 实施例 26. 含有本发明化合物的杀虫剂组合物的制备
(a) 油状悬浮液
按比例准备以下组分: 25% (重量百分比, 下同)化合物 1 -71中任一种化合物; 5%聚氧乙烯山梨醇六油酸酯; 70%高级脂肪族烃油。将各组分在沙磨中一起研 磨, 直到固体颗粒降至约 5微米以下为止。 所得的粘稠悬浮液可直接使用, 但 也可在水中乳化后使用。
(b) 水悬浮液
按比例准备以下组分: 25%化合物 1 -71 中任一种化合物; 3%水合硅镁土 (hydrate attapulgit) ; 10%木质素磺酸钙; 0.5%磷酸二氢钠; 61.5%水。 将各组分在 球磨机中一起研磨, 直到固体颗粒降至约 10微米以下为止。 该水悬浮液可直接使 用。
(c) 饵剂
按比例准备以下组分: 0. 1 -10%化合物 1 -71中任一种化合物; 80%小麦面粉; 19.9-10%糖蜜。 将这些组分完全混合, 按需要形成饵形状。 可食用饵可以分散到 卫生害虫所侵染的场所, 例如家居或工业场所, 诸如厨房、 医院或商店或户外区 域, 以通过口服摄入来防治害虫。 在本发明提及的所有文献都在本申请中引用作为参考, 就如同每一篇文献被 单独引用作为参考那样。 此外应理解, 在阅读了本发明的上述讲授内容之后, 本 领域技术人员可以对本发明作各种改动或修改, 这些等价形式同样落于本申请所 附权利要求书所限定的范围。

Claims

权 利 要 求
1. 一种具有通式 (A)所示结构的化合物, 或所述化合物的光学异构体、顺反 异构体或农药学上可接受的盐:
Figure imgf000026_0001
式中:
!^为含氮、 氧和 /或硫的五元或六元杂环基, ¾代的含氮、 氧和 /或硫的五元 或六元杂环基, 或者取代或未取代的苯基, 其中, 所述取代基为选自下组中的 一个或多个: 卤素, 4卤代烷基或 4氯代烷氧基;
R2、 R3各自独立地为 H, d_6烷基, 烯丙基, 苄基, 带 2-4个 C的烷氧基 烷基, 带 1-3个 C的烷氧基羰基, 苯氧羰基, 带 2-6个 C的炔基羰基, 带 2-3 个 C的烯基羰基, 带 3-6个 C的环烷基羰基, 苯甲酰基或取代的苯甲酰基, 呋 喃羰基,或 Ν,Ν-二甲基羰基,或者 R2和 R3共同构成 -CH2-CH2-或 -CH2-CH2-CH2-; -CH2-XR-CH2-, 其中 X为选自 N, O,或 S的杂原子, R是杂原子上的 d_6烷基 或烷氧基;
为 H, d_6烷基, 烯丙基, 烯基, 苄基, 含氮、 氧和 /或硫的五元或六元 杂环基, ¾代的含氮、氧和 /或硫的五元或六元杂环基,或取代或未取代的苯基;
R5和 R6各自独立地为 H, d_6烷基, 烯丙基, 苄基, 带 2-4个 C的烷氧基 烷基, 带 1-3个 C的烷氧基羰基, 苯氧羰基, 带 2-6个 C的炔基羰基, 带 2-3 个 C的烯基羰基, 带 3-6个 C的环烷基羰基, 苯甲酰基或取代的苯甲酰基, 磺 酰基, 含氮、 氧和 /或硫的五元或六元杂环羰基, ¾代的含氮、 氧和 /或硫的五 元或六元杂环羰基, 或 Ν,Ν-二甲基羰基, 或者 R5 和 R6 共同构成 -CH2-(CH2)n-CH2- (n = 0, 1, 2, 3, 4);
Y为硝基, 氰基, 三氟甲基, 三氟乙酰基, 或三氟甲磺酰基;
z为硝基, 氰基, 酯基, 酰胺基, 甲羧基, 甲羟基, 或三氟甲基。
2. 如权利要求 1所述的化合物、 或所述化合物的光学异构体、 顺反异构体 或农药学上可接受的盐, 其特征在于, 选自: 吡啶基、 噻唑基、 嘧啶基、 四 氢呋喃基、 噁唑基或其卤代物。
3. 如权利要求 1所述的化合物、 或所述化合物的光学异构体、 顺反异构体 或农药学上可接受的盐, 其特征在于, R2、 R3为氢或 (^_6烷基, 或者 R2和 R3 共同构成 -CH2-CH2-或 -CH2-CH2-CH2-。
4. 如权利要求 1所述的化合物、 或所述化合物的光学异构体、 顺反异构体 或农药学上可接受的盐, 其特征在于, R4为 H, d_6烷基, 取代或未取代的吡 啶基、 噻唑基、 嘧啶基、 四氢呋喃基、 噁唑基, 取代或未取代的苯基。
5. 如权利要求 1所述的化合物、 或所述化合物的光学异构体、 顺反异构体 或农药学上可接受的盐, 其特征在于, R5、 R6为氢, 磺酰基, 或羰基。
6. 如权利要求 1所述的化合物、 或所述化合物的光学异构体、 顺反异构体 或农药学上可接受的盐, 其特征在于, Y为硝基或氰基。
7. 如权利要求 1所述的化合物、 或所述化合物的光学异构体、 顺反异构体 或农药学上可接受的盐, 其特征在于, Z为硝基, 氰基, 酯基, 或三氟甲基。
8. 一种农用组合物, 其包含:
(a) 0.001-99.99重量%的权利要求 1-7中任一项所述的化合物、 其光学异构 体、 顺反异构体或农药学上可接受的盐、 或者它们的组合; 以及
(b) 农药学上可接受的载体和 /或赋形剂。
9. 如权利要求 8所述的农用组合物的用途, 其特征在于, 用于杀灭或预防 农业害虫、卫生害虫和危害动物健康的害虫;或用作用于杀灭或预防农业害虫、 卫生害虫和危害动物健康的杀虫剂组合物。
10. 如权利要求 1-7中任一项所述的化合物、 其光学异构体、 顺反异构体或 农药学上可接受的盐的制备方法, 所述方法包括, 在催化剂存在时使式 I的化 合物、 式 II的化合物和式 III的化合物在反应溶剂中反应得到式 A的化合物:
Figure imgf000027_0001
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