WO2014079354A1 - Acrylonitrile compounds and uses thereof - Google Patents

Acrylonitrile compounds and uses thereof Download PDF

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WO2014079354A1
WO2014079354A1 PCT/CN2013/087479 CN2013087479W WO2014079354A1 WO 2014079354 A1 WO2014079354 A1 WO 2014079354A1 CN 2013087479 W CN2013087479 W CN 2013087479W WO 2014079354 A1 WO2014079354 A1 WO 2014079354A1
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compound
mol
formula
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reaction
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PCT/CN2013/087479
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French (fr)
Chinese (zh)
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杨辉斌
李斌
宋玉泉
褚岩凤
王斌
刘红翼
冯聪
李琴
王洋
英君伍
陈霖
于海波
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中国中化股份有限公司
沈阳化工研究院有限公司
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Priority claimed from CN201210484457.5A external-priority patent/CN103833668B/en
Priority claimed from CN201210484570.3A external-priority patent/CN103833744B/en
Priority claimed from CN201210484280.9A external-priority patent/CN103833670B/en
Application filed by 中国中化股份有限公司, 沈阳化工研究院有限公司 filed Critical 中国中化股份有限公司
Publication of WO2014079354A1 publication Critical patent/WO2014079354A1/en

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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
    • A01N43/00—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds
    • A01N43/48—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with two nitrogen atoms as the only ring hetero atoms
    • A01N43/56—1,2-Diazoles; Hydrogenated 1,2-diazoles
    • 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
    • A01N43/72—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with nitrogen atoms and oxygen or sulfur atoms as ring hetero atoms
    • A01N43/74—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with nitrogen atoms and oxygen or sulfur atoms as ring hetero atoms five-membered rings with one nitrogen atom and either one oxygen atom or one sulfur atom in positions 1,3
    • A01N43/76—1,3-Oxazoles; Hydrogenated 1,3-oxazoles
    • 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
    • A01N43/72—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with nitrogen atoms and oxygen or sulfur atoms as ring hetero atoms
    • A01N43/74—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with nitrogen atoms and oxygen or sulfur atoms as ring hetero atoms five-membered rings with one nitrogen atom and either one oxygen atom or one sulfur atom in positions 1,3
    • A01N43/78—1,3-Thiazoles; Hydrogenated 1,3-thiazoles
    • 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
    • A01N47/00—Biocides, pest repellants or attractants, or plant growth regulators containing organic compounds containing a carbon atom not being member of a ring and having no bond to a carbon or hydrogen atom, e.g. derivatives of carbonic acid
    • A01N47/02—Biocides, pest repellants or attractants, or plant growth regulators containing organic compounds containing a carbon atom not being member of a ring and having no bond to a carbon or hydrogen atom, e.g. derivatives of carbonic acid the carbon atom having no bond to a nitrogen atom
    • A01N47/06—Biocides, pest repellants or attractants, or plant growth regulators containing organic compounds containing a carbon atom not being member of a ring and having no bond to a carbon or hydrogen atom, e.g. derivatives of carbonic acid the carbon atom having no bond to a nitrogen atom containing —O—CO—O— groups; Thio analogues thereof
    • 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
    • A01N53/00—Biocides, pest repellants or attractants, or plant growth regulators containing cyclopropane carboxylic acids or derivatives thereof
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D231/00—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings
    • C07D231/02—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings
    • C07D231/10—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
    • C07D231/12—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D231/00—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings
    • C07D231/02—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings
    • C07D231/10—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
    • C07D231/14—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members 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 ring carbon atoms
    • C07D231/16—Halogen atoms or nitro radicals
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D263/00—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings
    • C07D263/02—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings not condensed with other rings
    • C07D263/30—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
    • C07D263/32—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D277/00—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings
    • C07D277/02—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings
    • C07D277/20—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
    • C07D277/22—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
    • C07D277/30—Radicals substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D277/00—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings
    • C07D277/02—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings
    • C07D277/20—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
    • C07D277/32—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members 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 ring carbon atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
    • C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
    • C07D413/06—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
    • C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
    • C07D417/06—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms

Definitions

  • the invention belongs to the field of insecticides. Specifically, it relates to an acrylonitrile compound and its use.
  • the compound KC 4 has a high control effect against Myzus persicae at a concentration of 25 ppm.
  • CN101875633 discloses the acaricidal activity of 1-ethylpyrazoles, and KC 5 (No. 5 in the patent) has a control effect on cinnabarinus at a concentration of 2.5 ppm of more than 90%.
  • An object of the present invention is to provide a novel structure of an acrylonitrile compound which can be applied to the control of sanitary pests for agricultural, forestry or non-therapeutic purposes.
  • the present invention provides an acrylonitrile compound, as shown in Formula I: In the formula:
  • R is selected from C r C 6 fluorenyl, C r C 6 halo fluorenyl, C 3 -C 8 cycloalkyl or C r C 6 alkoxy or phenyl, and the hydrogen on the phenyl ring is further substituted by the following substituent Substitution: halogen, cyano, nitro, methyl or halomethyl;
  • A is selected from the following groups:
  • X 2 is selected from the group consisting of hydrogen, halogen, cyano or methyl
  • 3 ⁇ 4 is selected from the group consisting of chlorine, trifluoromethyl or nitro;
  • R 2 is selected from H or halogen
  • R is selected from -C 6 fluorenyl, C r C 6 halodecyl, C 3 -C 8 cyclodecyl or -C 6 alkoxy or phenyl;
  • A is selected from the following groups:
  • X 2 is selected from the group consisting of hydrogen, halogen or methyl
  • X 3 is selected from chlorine or trifluoromethyl
  • Q is selected from the following groups: Selected from H or halogen;
  • R 2 is selected from H or halogen
  • R is selected from C 3 -C 6 alkyl, C 3 -C 6 haloalkyl or C r C 4 alkoxy;
  • A is selected from the following groups:
  • Xi is selected from chlorine
  • X 2 is selected from hydrogen
  • ⁇ 3 is selected from trifluoromethyl
  • R 2 is selected from H, fluorine or chlorine
  • Alkyl refers to a straight or branched form, such as methyl, ethyl, n-propyl, isopropyl, and the like.
  • the cycloalkyl group includes a cyclopropyl group, a cyclobutyl group, a cyclopropylmethyl group, a methylcyclopropyl group and the like.
  • the haloalkyl group means a group in which an alkyl group is substituted by one or more halogen atoms, such as a chloroethyl group, a trifluoromethyl group or the like.
  • the alkoxy group means a group having an oxygen atom bonded to the terminal of the alkyl group, and examples thereof include a methoxy group, an ethoxy group, a n-propoxy group, an isopropoxy group and the like.
  • Halogen means fluorine, chlorine, bromine or iodine.
  • the stereoisomer means that in the formula I, the substituents CN and OCOR on the carbon-carbon double bond are on the same side (Z configuration) or both sides (E configuration) of the double bond.
  • the compounds of formula I of the present invention can be prepared by the following methods, wherein the groups in the formula are as defined above.
  • L represents a suitable leaving group such as chlorine, bromine or p-toluenesulfonyloxy.
  • the compound of the formula II is reacted with a compound of the formula III in a suitable solvent at a temperature of from -10 ° C to reflux temperature for from 0.5 to 48 hours to give the object compound I.
  • suitable solvents are selected from the group consisting of dichloromethane, chloroform, carbon tetrachloride, hexane, benzene, toluene, ethyl acetate, acetonitrile, tetrahydrofuran, dioxane, hydrazine, hydrazine-dimethylformamide or dimethylene. Sulfone and the like.
  • Suitable bases may be selected from organic bases such as triethylamine, hydrazine, hydrazine-dimethylaniline, pyridine, sodium methoxide, sodium t-butoxide or potassium t-butoxide; or inorganic bases such as sodium hydroxide, potassium hydroxide , sodium bicarbonate, sodium carbonate or sodium hydride.
  • the compounds of formula I are stereoisomeric depending on the difference in reaction conditions or the starting materials.
  • the substituents on the carbon-carbon double bond CN and OCOR are on the same side of the double bond ( ⁇ configuration) or on both sides ( ⁇ configuration).
  • An isomer excess product or a single isomer can be obtained by selecting an appropriate starting material or controlling the reaction conditions.
  • the single isomer can also be obtained by conventional means of separation of the crude product, for example by column chromatography, recrystallization, or the like.
  • the structure of these isomers can be determined by conventional analytical methods such as X-ray single crystal diffraction, nuclear magnetic resonance, and the like.
  • ⁇ represents a suitable leaving group such as chlorine, bromine, pyrazolyl, imidazolylmethoxy, ethoxy or p-toluenesulfonyloxy and the like.
  • the compound of the formula IV is reacted with a compound of the formula V in a suitable solvent in the presence of a base at a temperature of from -10 ° C to the boiling point for 0.5 to 48 hours to obtain a compound of the formula II.
  • Suitable solvents are mainly selected from the group consisting of: dichloromethane, chloroform, carbon tetrachloride, benzene, toluene, methanol, ethanol, ethyl acetate, acetonitrile, tetrahydrofuran, dioxane, hydrazine, hydrazine-dimethylformamide, Methyl sulfoxide, 2-methylpentane, methylcyclopentane, hexane, cyclohexane, methylcyclohexane, heptane, octane, decane, dibutyl ether, ethylene glycol dimethyl ether , ethylene glycol diethyl ether, ethylene glycol dibutyl ether, ethylene glycol monomethyl ether, ethylene glycol monoethyl ether, ethylene glycol monobutyl ether, etc., or two or three different a mixture of solvents.
  • Suitable bases are selected from the group consisting of organic bases such as triethylamine, hydrazine, hydrazine-dimethylaniline, pyridine, 2-methylpyridine, 3-methylpyridine, 4-methylpyridine, 5-ethyl-2-methyl Pyridine, 2,3-lutidine, 2,4-lutidine, 3,5-lutidine, 2,6-lutidine, 2,4,6-trimethylpyridine, quin Or a base such as sodium hydroxide, potassium hydroxide, sodium carbonate or potassium carbonate.
  • organic bases such as triethylamine, hydrazine, hydrazine-dimethylaniline, pyridine, 2-methylpyridine, 3-methylpyridine, 4-methylpyridine, 5-ethyl-2-methyl Pyridine, 2,3-lutidine, 2,4-lutidine, 3,5-lutidine, 2,6-lutidine, 2,4,6-trimethylpyridine, quin
  • a base such as sodium hydroxide, potassium hydroxide, sodium carbonate or
  • Tables 1 - 3 list the structural and physical properties of some of the compounds.
  • Compound 1-151 7.95 (s, IH), 7.39 (m, 3H), 2.26 (s, 3H), 1.72 (q, 2H), 1.30 (s, 6H), 0.93 (t, 3H).
  • Compound 1-158 7.95 (d, 1H), 7.70 (m, 2H), 7.48 (m, 2H), 7.35 (m, IH), 6.75 (d, IH), 2.61 (s, 3H), 1.29 (s , 6H).
  • Compound 2-3 7.90 (m, 2H), 7.70 (s, 1H), 7.48 (m, 3H), 6.54 (s, 1H), 4.24 (q, 2H), 2.59 (t, 2H) (s, 3H) ), 1.66 (sext, 2H), 1.49 (t, 3H), 0.91 (t, 3H).
  • Compound 2-5 7.91 (m, 2H), 7.68 (s, 1H), 7.48 (m, 3H), 6.48 (s, IH), 4.26 (q, 2H), 2.60 (hept., 1H), 2.32 ( s, 3H), 1.51 (t, 3H), 1.21 (d, 6H).
  • Compound 2-66 7.94 (s, IH), 7.43 (m, IH), 7.07 (m, 2H), 6.63 (s, IH), 4.26 (q, 2H), 4.25 (q, 2H),
  • Compound 2-68 7.93 (s, 1H), 7.43 (m, 1H), 7.06 (m, 2H), 6.63 (s, 1H), 4.89 (hept., 1H), 4.24 (q, 2H), 2.32 ( s, 3H), 1.47 (t, 3H), 1.24 (d, 6H).
  • Compound 2-104 8.08 (s, 1H), 8.07 (m, IH), 7.46 (m, 1H), 7.25 (m, 2H), 6.34 (s, 1H), 4.25 (q, 2H), 2.30 (s , 3H), 1.66 (q, 2H), 1.53 (t, 3H), 1.28 (s, 6H), 0.79 (t, 3H;).
  • Compound 2-116 8.10 (s, 1H), 7.95 (m, 1H), 7.51 (m, 1H), 7.40 (m, 2H), 6.34 (s, 1H), 4.25 (q, 2H), 2.30 (s , 3H), 1.65 (q, 2H), 1.53 (t, 3H), 1.26 (s, 6H), 0.78 (t, 3H;).
  • Compound 2-138 8.13 (s, IH), 7.46 (m, IH), 7.07 (m, 2H), 6.49 (s, IH), 4.24 (q, 2H), 2.90 (hept., IH), 2.31 ( s, 3H), 1.49 (t, 3H), 1.25 (d, 6H).
  • Compound 2-202 7.99 (d, IH), 7.72 (m, 2H), 7.47 (m, 2H), 7.38 (m, IH), 6.83 (d, IH), 6.61 (s, IH), 4.26 (q , 2H), 3.99 (d, 2H), 2.32 (s, 3H), 2.01 (hept., 1H), 1.48 (t, 3H), 0.92 (d, 6H).
  • Compound 3-11 7.96-7.90 (m, 2H), 7.80-7.77 (m, 2H), 7.72-7.60 (m, 3H), 7.47-7.44 (m, 3H), 3.05-2.91 (m, IH), 1.80-1.74 (m, 4H), 1.65-1.54 (m, 4H).
  • Compound 3-175 8.00 (d, 1H), 7.90 (d, 1H), 7.79 (d, 1H), 7.72-7.65 (m, 4H), 7.52 (d, 1H),
  • the acrylonitrile compound of the invention has high insecticidal activity and can control Plutella xylostella, Spodoptera exigua, Spodoptera litura, Helicoverpa armigera, Grass armyworm, Spodoptera litura, Bean, Soybean, Beet, and cotton aphid , apple tart, peach aphid, corn bran, whitefly, leafhopper, planthopper, rice planthopper, whitefly, cotton net, tomato blind dragonfly, rice green grass, rice skunk, cotton scorpion horse, hummer, Soybeans, potato beetles, armor, flies, mosquitoes and other pests.
  • the acrylonitrile compound of the present invention has unexpectedly high insecticidal activity as compared with the known acrylonitrile compound. Accordingly, the present invention also encompasses the use of a compound of formula I for controlling pests.
  • the present invention also encompasses pesticidal compositions having a compound of formula I as an active ingredient.
  • the active ingredient in the pesticidal composition is present in an amount between 1 and 99% by weight.
  • agricultural, forestry or hygienic acceptable carriers are also included in the pesticidal composition.
  • the compositions of the invention may be administered in the form of a formulation.
  • the compound of the formula I is dissolved or dispersed in the carrier as an active ingredient or formulated into a formulation for easier dispersion when used as an insecticide.
  • These chemicals can be formulated as wettable powders or creams.
  • at least one liquid or solid carrier is added, and a suitable surfactant may be added as needed.
  • the technical solution of the present invention also includes a method of controlling pests:
  • the insecticidal composition of the present invention is applied to a pest to be controlled or a growth medium thereof.
  • a more suitable effective amount is usually selected from 10 g to 1000 g per hectare, and an effective amount is preferably 50 g to 500 g per hectare.
  • one or more other fungicides, insecticides, herbicides, plant growth regulators or fertilizers may be added to the pesticidal composition of the invention, thereby producing additional The advantages and effects.
  • the obtained aqueous phase was acidified with concentrated hydrochloric acid to pH 2-3, and extracted with 3 ⁇ 150 ml of ethyl acetate. After washing with a saturated aqueous solution of sodium chloride (150 ml), dried over anhydrous magnesium sulfate and evaporated. 2-(2-Phenylthiazol-4-yl)acrylonitrile, yellow solid, yield 51%.
  • aqueous phase was adjusted to pH 2 to 3 with hydrochloric acid, and then extracted with ethyl acetate (3 ⁇ 25 ml). 3-methylpyrazol-5-yl)-2-(2-phenylthiazol-4-yl)acrylonitrile, brown oil, yield 57%.
  • aqueous phase was acidified with concentrated hydrochloric acid to pH 2-3, extracted with 3 ⁇ 100 ml of ethyl acetate, and the organic phase was saturated aqueous sodium hydrogen carbonate (100) ML), saturated sodium chloride solution After washing (100 ml), dried over anhydrous magnesium sulfate and evaporated. Acrylonitrile, yellow oil, yield 61%.
  • reaction mixture was cooled to 30 ° C or less, and the reaction mixture was poured into 50 ml of water and extracted with ethyl acetate (100 ml). The obtained organic layer was washed with saturated aqueous sodium hydrogen carbonate (100 ml) and saturated aqueous sodium chloride (100 ml) Drying over anhydrous magnesium sulfate, EtOAc (EtOAc m.) 39%.
  • reaction mixture was poured into 50 ml of water and washed with ethyl acetate 2x 20 ml, and the organic phase was discarded.
  • the aqueous phase was adjusted to pH 2 to 3 with hydrochloric acid to precipitate a solid, which was filtered and dried to give 2.00 g of intermediate 3-hydroxy-3-(2-chloro-4-methylthiazol-5-yl)-2-(2) -(2,6-Difluorophenyl)oxazol-4-yl)acrylonitrile, yellow solid, yield 58%.
  • reaction mixture was poured into 50 ml of water, and washed with ethyl acetate 2 ⁇ 20 ml, and the organic phase was discarded.
  • the aqueous phase was adjusted to pH 2 to 3 with hydrochloric acid to precipitate a solid, which was filtered and dried to give 5.20 g of intermediate 3-hydroxy-3-(1-ethyl-3-methyl-1H-pyrazol-5-yl) 2-(2-(2,6-Difluorophenyl)oxazol-4-yl)acrylonitrile, yellow solid, yield 80%.
  • reaction mixture was poured into 50 ml of water and extracted with ethyl acetate (2 ⁇ 50 ml).
  • the obtained organic phase was saturated with 15 ml of saturated aqueous sodium hydrogen carbonate After washing with a sodium aqueous solution, dried over anhydrous magnesium sulfate, and evaporated, evaporated, evaporated, evaporated, , yield 67%.
  • reaction mixture was poured into 50 ml of water and extracted with ethyl acetate (2 ⁇ 50 ml). After washing with 15 ml of a saturated aqueous solution of sodium hydrogencarbonate and brine (25 ml of saturated aqueous sodium chloride), dried over anhydrous magnesium sulfate and evaporated. 1:5) 0.33 g of compound 2-287, yellow oil, yield 85%.
  • aqueous phase was adjusted to pH 2 to 3 with hydrochloric acid to precipitate a solid, which was filtered and dried to give 2.00 g of 3-hydroxy-3-(2-trifluoromethylphenyl)-2-(2-(2, 6-) Fluorophenyl)oxazole-4-yl)acrylonitrile, yellow solid, yield 67%.
  • reaction mixture was poured into 50 ml of water and washed with ethyl acetate 2x 20 ml, and the organic phase was discarded.
  • the aqueous phase was adjusted to pH 2 to 3 with hydrochloric acid, and then extracted with ethyl acetate (3 ⁇ 25 ml), dried over anhydrous magnesium sulfate.
  • the obtained aqueous phase was acidified with concentrated hydrochloric acid to pH 2-3, extracted with 3 ⁇ 100 ml of ethyl acetate After washing with a saturated aqueous solution of sodium chloride (100 ml), dried over anhydrous magnesium sulfate - pyrazol-3-yl)-3-hydroxyacrylonitrile, yellow solid, yield 85%, m.p.: 118-120.
  • the original pharmaceutically acceptable acetone or dimethyl sulfoxide is dissolved, and then 1% is used.
  • the Tween 80 solution is prepared to a desired concentration of 50 ml of the test solution, and the content of acetone or dimethyl sulfoxide in the solution is not more than 10%.
  • the insecticidal mortality activity was graded as follows: A: 100%; B: 99-80; C: 79-60; D: 59%-0.
  • the cabbage leaves were punched into 2 cm diameter discs with a puncher and sprayed with Airbrush at a pressure of 10 psi (about 0.7 kg/cm 2 ). The spray was sprayed on the front and back of each leaf with a spray volume of 0.5 mL. After the dryness, 10 heads of 2nd intestines were connected to each treatment, and each treatment was repeated 3 times. After the treatment, the cells were cultured at 25 ° C and a relative humidity of 60 to 70%, and the number of viable animals was investigated after 72 hours, and the mortality was calculated and classified.
  • the following compounds had better control effects on Plutella xylostella at a concentration of 600 ppm, and the mortality rate was above B: 1-2, 1-3, 1-4, 1-10, 1-16 , 1-17, 1-22, 1-23, 1-25, 1-33, 1-37, 1-38,
  • the corn leaves were cut into 2 cm sections and sprayed with Airbrush at a pressure of 10 psi (about 0.7 kg/cm 2 ).
  • the spray was sprayed on the front and back of each leaf section with a spray volume of 0.5 mL.
  • 10 heads of 2nd intestines were connected to each treatment, and each treatment was repeated 3 times.
  • the cells were cultured at 25 ° C and a relative humidity of 60 to 70%, and the number of viable animals was investigated after 72 hours, and the mortality was calculated and classified.
  • the following compounds had better control effect against armyworms at a concentration of 600 ppm, and the mortality rate was above grade B: 1-2, 1-3, 1-4, 1-5, 1-16 , 1-22, 1-23, 1-25, 1-37, 1-38, 1-44, 1-45, 1-47,
  • the following compounds had better control effect against armyworms at a concentration of 100 ppm, and the mortality rate was above grade B: 1-37, 1-38, 1-47, 1-48, 1-53 , 1-63, 1-64, 1-151, 2-48, 2-173, 2-174, 2-247, 3-2, 3-3, 3-4, 3-5, 3-6, 3 -7, 3-8, 3-22, 3-15, 3-17, 3-26, 3-28, 3-34, 3-35, 3-44, 3-45, 3-47, 3-52 , 3-54, 3-57, 3-59, 3-65, 3-67, 3-79, 3-98, 3-115, 3-117, 3-123, 3-125, 3-170, 3 -175.

Abstract

Disclosed are acrylonitrile compounds with novel structure or stereoisomers thereof, and the structure of the compounds is as shown by the general formula (I): In the formula: R is selected from C1-C6 alkyl, C1-C6 haloalkyl, C3-C8 cycloalkyl, C1-C6 alkoxy or phenyl, and hydrogens on the benzene ring can be further replaced by the following substituents: halogen, cyano, nitro, methyl or halomethyl; A is selected from the following groups: formula (A1), formula (A2), or formula (A3); Q is selected from the following groups: formula (Q1), formula (Q2), or formula (Q3); or stereoisomers thereof. See the definitions of the groups in the formulas in the specification. The compounds of the general formula (I) have excellent insecticidal activity, and can be used to control pests.

Description

丙烯腈类化合物及其应用  Acrylonitrile compounds and their applications
技术领域 Technical field
本发明属于杀虫剂领域。 具体涉及一种丙烯腈类化合物及其应用。  The invention belongs to the field of insecticides. Specifically, it relates to an acrylonitrile compound and its use.
背景技术  Background technique
由于杀虫剂在使用一段时间后， 害虫会对其产生抗性， 因此， 需要不断发明新型的和改 进的具杀虫活性的化合物和组合物。 同时， 随着人们对农畜产品等日益增长的需要和对环境 保护的日益重视， 也一直需要使用成本更低、 对环境友好的新的杀虫剂。  Since insecticides are resistant to insecticides after a period of use, it is necessary to continuously invent new and improved insecticidal compounds and compositions. At the same time, with the growing demand for agricultural and livestock products and the increasing emphasis on environmental protection, there is always a need to use new, less costly, environmentally friendly pesticides.
日产化学工业株式会社在 WO9740009 申请中， 公开了具有杀虫、 杀螨或杀菌活性的乙 烯衍生物， 报道了下列化合物 Kd (专利中编号 11-63 )禾 B KC2 (专利中编号 11-15 ) 的杀虫活 性； 在 JP2005008628申请中， 报道了化合物 KC3 (专利中编号 1 ) 的制备及杀虫活性。 它们 在 500 ppm的浓度下对桃蚜防效均在 80%以上。在 WO2007100160和 WO2007100161申请中， 进一步公开了化合物 KC4 (专利中编号 1 ) 的制备、 杀虫活性及合成工艺研究， 化合物 KC4 在 25 ppm的浓度下对桃蚜具有高的防治效果。 CN101875633公开了 1-乙基吡唑类化合物的 杀螨活性， KC5 (专利中编号 5 ) 在 2.5 ppm浓度下对朱砂叶螨防效在 90%以上。 Nissan Chemical Industry Co., Ltd., in the application of WO9740009, discloses an ethylene derivative having insecticidal, acaricidal or bactericidal activity, and the following compound Kd (patent number 11-63) and B KC 2 (patent number 11-15) is reported. Insecticidal activity; In the application of JP2005008628, the preparation and insecticidal activity of the compound KC 3 (No. 1 in the patent) was reported. They are more than 80% effective against peach aphid at a concentration of 500 ppm. In WO2007100160 and WO2007100161 applications further disclosed Preparation, insecticidal activity and synthesis of Compound KC 4 (Patent No. 1), the compound KC 4 has a high control effect against Myzus persicae at a concentration of 25 ppm. CN101875633 discloses the acaricidal activity of 1-ethylpyrazoles, and KC 5 (No. 5 in the patent) has a control effect on cinnabarinus at a concentration of 2.5 ppm of more than 90%.
Figure imgf000003_0001
Figure imgf000003_0001
发明内容  Summary of the invention
本发明的目的在于提供一种结构新颖的丙烯腈类化合物， 它可应用于农业、 林业或非治 疗目的的卫生上害虫的防治。  SUMMARY OF THE INVENTION An object of the present invention is to provide a novel structure of an acrylonitrile compound which can be applied to the control of sanitary pests for agricultural, forestry or non-therapeutic purposes.
本发明的技术方案如下：  The technical solution of the present invention is as follows:
本发明提供了一种丙烯腈类化合物， 如通式 I所示:
Figure imgf000003_0002
式中： The present invention provides an acrylonitrile compound, as shown in Formula I:
Figure imgf000003_0002
In the formula:
R选自 CrC6垸基、 CrC6卤代垸基、 C3-C8环烷基或 CrC6烷氧基或苯基， 苯环上的氢还 进一步被如下取代基取代： 卤素、 氰基、 硝基、 甲基或卤代甲基； R is selected from C r C 6 fluorenyl, C r C 6 halo fluorenyl, C 3 -C 8 cycloalkyl or C r C 6 alkoxy or phenyl, and the hydrogen on the phenyl ring is further substituted by the following substituent Substitution: halogen, cyano, nitro, methyl or halomethyl;
A选自如下基团：  A is selected from the following groups:
Figure imgf000004_0001
选自氯、 溴或碘；
Figure imgf000004_0001
Selected from chlorine, bromine or iodine;
X2选自氢、 卤素、 氰基或甲基; X 2 is selected from the group consisting of hydrogen, halogen, cyano or methyl;
¾选自氯、 三氟甲基或硝基；  3⁄4 is selected from the group consisting of chlorine, trifluoromethyl or nitro;
Q选自如下基  Q is selected from the following bases
Figure imgf000004_0002
Figure imgf000004_0002
选自 H、 卤素、 甲基或三氟甲基；  Selected from H, halogen, methyl or trifluoromethyl;
R2选自 H或卤素； R 2 is selected from H or halogen;
或其立体异构体。  Or a stereoisomer thereof.
本发明进一步优选的化合物为， 通式 I中：  Further preferred compounds of the invention are those of formula I:
R选自 -C6垸基、 CrC6卤代垸基、 C3-C8环垸基或 -C6烷氧基或苯基; R is selected from -C 6 fluorenyl, C r C 6 halodecyl, C 3 -C 8 cyclodecyl or -C 6 alkoxy or phenyl;
A选自如下基团：  A is selected from the following groups:
Figure imgf000004_0003
Figure imgf000004_0003
选自氯或溴；  Selected from chlorine or bromine;
X2选自氢、 卤素或甲基； X 2 is selected from the group consisting of hydrogen, halogen or methyl;
X3选自氯或三氟甲基； X 3 is selected from chlorine or trifluoromethyl;
Q选自如下基团：
Figure imgf000004_0004
选自 H或卤素； Q is selected from the following groups:
Figure imgf000004_0004
Selected from H or halogen;
R2选自 H或卤素； R 2 is selected from H or halogen;
或其立体异构体。  Or a stereoisomer thereof.
本发明更进一步优选的化合物为， 通式 I中：  Further preferred compounds of the invention are those of formula I:
R选自 C3-C6烷基、 C3-C6卤代烷基或 CrC4烷氧基; R is selected from C 3 -C 6 alkyl, C 3 -C 6 haloalkyl or C r C 4 alkoxy;
A选自如下基团：  A is selected from the following groups:
Figure imgf000005_0001
Figure imgf000005_0001
Xi选自氯；  Xi is selected from chlorine;
X2选自氢； X 2 is selected from hydrogen;
χ3选自三氟甲基; χ 3 is selected from trifluoromethyl;
Q选自如下基  Q is selected from the following bases
Figure imgf000005_0002
Figure imgf000005_0002
选自 H、 氟或氯；  Selected from H, fluorine or chlorine;
R2选自 H、 氟或氯； R 2 is selected from H, fluorine or chlorine;
或其立体异构体。  Or a stereoisomer thereof.
上面给出的通式 I化合物的定义中， 汇集所用术语一般定义如下：  In the definitions of the compounds of formula I given above, the terms used in the collection are generally defined as follows:
烷基是指直链或支链形式， 例如甲基、 乙基、 正丙基、 异丙基等。 环烷基包括环丙基、 环丁基、 环丙基甲基、 甲基环丙基等。 卤代烷基是指烷基被一个或多个卤原子取代的基团， 如氯乙基、 三氟甲基等。 烷氧基是指烷基末端连有氧原子的基团， 例如甲氧基、 乙氧基、 正 丙氧基、 异丙氧基等。 卤素是指氟、 氯、 溴、 碘。 立体异构体是指在式 I中， 碳碳双键上的 取代基 CN和 OCOR在双键的同一侧 （Z构型） 或两侧 （E构型）。  Alkyl refers to a straight or branched form, such as methyl, ethyl, n-propyl, isopropyl, and the like. The cycloalkyl group includes a cyclopropyl group, a cyclobutyl group, a cyclopropylmethyl group, a methylcyclopropyl group and the like. The haloalkyl group means a group in which an alkyl group is substituted by one or more halogen atoms, such as a chloroethyl group, a trifluoromethyl group or the like. The alkoxy group means a group having an oxygen atom bonded to the terminal of the alkyl group, and examples thereof include a methoxy group, an ethoxy group, a n-propoxy group, an isopropoxy group and the like. Halogen means fluorine, chlorine, bromine or iodine. The stereoisomer means that in the formula I, the substituents CN and OCOR on the carbon-carbon double bond are on the same side (Z configuration) or both sides (E configuration) of the double bond.
本发明的通式 I化合物可由如下方法制备， 反应式中各基团定义同前。
Figure imgf000005_0003
The compounds of formula I of the present invention can be prepared by the following methods, wherein the groups in the formula are as defined above.
Figure imgf000005_0003
II III I  II III I
式中： L代表合适的离去基团， 如氯、 溴或对甲苯磺酰氧基等。  Wherein: L represents a suitable leaving group such as chlorine, bromine or p-toluenesulfonyloxy.
通式 II化合物与通式 III化合物在适宜的溶剂中、 温度为 -10°C到回流温度下反应 0.5-48 小时制得目标化合物 I。 适宜的溶剂选自二氯甲烷、 氯仿、 四氯化碳、 己烷、 苯、 甲苯、 乙酸乙酯、 乙腈、 四氢 呋喃、 二氧六环、 Ν, Ν-二甲基甲酰胺或二甲基亚砜等。 The compound of the formula II is reacted with a compound of the formula III in a suitable solvent at a temperature of from -10 ° C to reflux temperature for from 0.5 to 48 hours to give the object compound I. Suitable solvents are selected from the group consisting of dichloromethane, chloroform, carbon tetrachloride, hexane, benzene, toluene, ethyl acetate, acetonitrile, tetrahydrofuran, dioxane, hydrazine, hydrazine-dimethylformamide or dimethylene. Sulfone and the like.
加入适宜的碱类物质对反应有利。 适宜的碱可以选自有机碱， 例如三乙胺、 Ν, Ν-二甲基 苯胺、 吡啶、 甲醇钠、 叔丁醇钠或叔丁醇钾等； 或无机碱如氢氧化钠、 氢氧化钾、 碳酸氢钠、 碳酸钠或氢化钠等。  The addition of a suitable base material is advantageous for the reaction. Suitable bases may be selected from organic bases such as triethylamine, hydrazine, hydrazine-dimethylaniline, pyridine, sodium methoxide, sodium t-butoxide or potassium t-butoxide; or inorganic bases such as sodium hydroxide, potassium hydroxide , sodium bicarbonate, sodium carbonate or sodium hydride.
根据反应条件的差异或起始原料的不同， 通式 I化合物存在立体异构现象。 例如碳碳双 键上的取代基 CN和 OCOR在双键的同一侧 （Ζ构型） 或两侧 （Ε构型） 。 通过选择适当的 起始原料或控制反应条件， 可以得到一种异构体过量的产物或单一异构体。 也可以通过对粗 产物进行常规手段的分离， 例如通过柱色谱、 重结晶等方法， 得到单一异构体。 这些异构体 的结构可通过 X-射线单晶衍射， 核磁共振等常规分析方法确定。  The compounds of formula I are stereoisomeric depending on the difference in reaction conditions or the starting materials. For example, the substituents on the carbon-carbon double bond CN and OCOR are on the same side of the double bond (Ζ configuration) or on both sides (Ε configuration). An isomer excess product or a single isomer can be obtained by selecting an appropriate starting material or controlling the reaction conditions. The single isomer can also be obtained by conventional means of separation of the crude product, for example by column chromatography, recrystallization, or the like. The structure of these isomers can be determined by conventional analytical methods such as X-ray single crystal diffraction, nuclear magnetic resonance, and the like.
通式 III化合物有市售。  Compounds of formula III are commercially available.
通式 II化合物的制备方法如下：
Figure imgf000006_0001
式中： ！^代表合适的离去基团， 如氯、 溴、 吡唑基、 咪唑基 甲氧基、 乙氧基或对甲苯 磺酰氧基等。 The preparation method of the compound of the general formula II is as follows:
Figure imgf000006_0001
In the formula: ! ^ represents a suitable leaving group such as chlorine, bromine, pyrazolyl, imidazolylmethoxy, ethoxy or p-toluenesulfonyloxy and the like.
通式 IV化合物与通式 V化合物在适宜的溶剂中、 在碱的存在下、 温度为 -10°C到沸点下 反应 0.5-48小时制得通式化合物 II。  The compound of the formula IV is reacted with a compound of the formula V in a suitable solvent in the presence of a base at a temperature of from -10 ° C to the boiling point for 0.5 to 48 hours to obtain a compound of the formula II.
适宜的溶剂主要选自： 二氯甲烷、 氯仿、 四氯化碳、 苯、 甲苯、 甲醇、 乙醇、 乙酸乙酯、 乙腈、 四氢呋喃、 二氧六环、 Ν, Ν-二甲基甲酰胺、 二甲基亚砜、 2-甲基戊烷、 甲基环戊烷、 己烷、 环己烷、 甲基环己烷、 庚烷、 辛烷、 壬烷、 丁醚、 乙二醇二甲基醚、 乙二醇二乙基醚、 乙二醇二丁基醚、 乙二醇单甲基醚、 乙二醇单乙基醚、 乙二醇单丁基醚等， 或者如上两种或 三种不同溶剂的混合物。  Suitable solvents are mainly selected from the group consisting of: dichloromethane, chloroform, carbon tetrachloride, benzene, toluene, methanol, ethanol, ethyl acetate, acetonitrile, tetrahydrofuran, dioxane, hydrazine, hydrazine-dimethylformamide, Methyl sulfoxide, 2-methylpentane, methylcyclopentane, hexane, cyclohexane, methylcyclohexane, heptane, octane, decane, dibutyl ether, ethylene glycol dimethyl ether , ethylene glycol diethyl ether, ethylene glycol dibutyl ether, ethylene glycol monomethyl ether, ethylene glycol monoethyl ether, ethylene glycol monobutyl ether, etc., or two or three different a mixture of solvents.
加入适宜的碱类物质对反应有利。 适宜的碱选自有机碱如三乙胺、 Ν, Ν-二甲基苯胺、 吡 啶、 2-甲基吡啶、 3-甲基吡啶、 4-甲基吡啶、 5-乙基 -2-甲基吡啶、 2, 3-二甲基吡啶、 2, 4-二甲 基吡啶、 3, 5-二甲基吡啶、 2, 6-二甲基吡啶、 2, 4, 6-三甲基吡啶、 喹啉、 甲醇钠、 乙醇钠、 叔 丁醇钠或叔丁醇钾等， 或无机碱如氢氧化钠、 氢氧化钾、 碳酸钠或碳酸钾等。  The addition of a suitable base material is advantageous for the reaction. Suitable bases are selected from the group consisting of organic bases such as triethylamine, hydrazine, hydrazine-dimethylaniline, pyridine, 2-methylpyridine, 3-methylpyridine, 4-methylpyridine, 5-ethyl-2-methyl Pyridine, 2,3-lutidine, 2,4-lutidine, 3,5-lutidine, 2,6-lutidine, 2,4,6-trimethylpyridine, quin Or a base such as sodium hydroxide, potassium hydroxide, sodium carbonate or potassium carbonate.
通式 IV化合物的具体制备 WO9740009、 DE2633992中描述的操作方法。  Specific Preparation of Compounds of Formula IV The method of operation described in WO9740009, DE2633992.
通式 V化合物的具体制备参见 Tetrahedron Lett., 2005, 46, 2251， J. Med. Chem., 1973, 16, 978， US 6096898， CN101875633。  For the specific preparation of compounds of formula V, see Tetrahedron Lett., 2005, 46, 2251, J. Med. Chem., 1973, 16, 978, US 6096898, CN101875633.
表 1-表 3列出了部分化合物的结构和物理性质。 Tables 1 - 3 list the structural and physical properties of some of the compounds.
Figure imgf000007_0001
Figure imgf000007_0001
) ) ) )
Figure imgf000007_0002
Figure imgf000008_0001
-58 Qi F CI / Z/E=3: l 黄色固体 （129-13ΓΟ
Figure imgf000007_0002
Figure imgf000008_0001
-58 Qi F CI / Z/E=3: l Yellow solid (129-13ΓΟ)
CICI
-59 Qi F CI H / Z或 E-59 Qi F CI H / Z or E
-60 Qi F CI Z或 E-60 Qi F CI Z or E
-61 Qi F CI ) Z或 E-61 Qi F CI ) Z or E
-62 Qi F CI OCH3 Z或 E-62 Qi F CI OCH 3 Z or E
-63 Qi F CI OCH2CH3 Z/E= l:3 黄色固体 （105-107°C )-64 Qi F CI OCH(CH3)2 Z/E= l:3 黄色固体 （ 87-89 °C )-65 Qi CI CI CH3 Z或 E-63 Qi F CI OCH 2 CH 3 Z/E= l:3 yellow solid (105-107°C)-64 Qi F CI OCH(CH 3 ) 2 Z/E= l:3 yellow solid ( 87-89 ° C )-65 Qi CI CI CH 3 Z or E
-66 Qi CI CI C(CH3)3 Z或 E-66 Qi CI CI C(CH 3 ) 3 Z or E
-67 Qi CI CI / Z或 E -68 Qi CI CI H 尸 Z或 E-67 Qi CI CI / Z or E -68 Qi CI CI H Corpse Z or E
-69 Qi CI CI M Z或 E-69 Qi CI CI M Z or E
-70 Qi CI CI ) Z或 E-70 Qi CI CI ) Z or E
-71 Qi CI CI 0CH3 Z或 E-71 Qi CI CI 0CH3 Z or E
-72 Q2 H H CH3 Z或 E-72 Q 2 HH CH 3 Z or E
-73 Q2 H H C(CH3)3 E 黄色固体 （ 97-99 °C )-74 Q2 H H C(CH3)3 Z 黄色固体 （114-116°C )-75 Q2 H H / E 白色固体 (85-86°C ) -76 Q2 H H / Z 蜡状固体 -77 Q2 H H H 尸 Z或 E-73 Q 2 HHC(CH 3 ) 3 E Yellow solid ( 97-99 ° C )-74 Q 2 HHC(CH 3 ) 3 Z Yellow solid (114-116 ° C)-75 Q 2 HH / E White solid ( 85-86°C ) -76 Q 2 HH / Z Waxy Solid -77 Q 2 HHH Corpse Z or E
-78 Q2 H H M Z或 E-78 Q 2 HHMZ or E
-79 Q2 H H ) Z或 E-79 Q 2 HH ) Z or E
-80 Q2 H H 0CH3 Z或 E-80 Q 2 HH 0CH3 Z or E
-81 Q2 H H OCH2CH3 E 黄色固体 （ 104-105 °C )-82 Q2 H H OCH2CH3 Z-81 Q 2 HH OCH 2 CH 3 E Yellow solid (104-105 °C)-82 Q 2 HH OCH 2 CH 3 Z
-83 Q2 H H OCH(CH3)2 E 白色固体 ( 103-104 °C )-84 Q2 H H OCH(CH3)2 Z-83 Q 2 HH OCH(CH 3 ) 2 E White solid ( 103-104 ° C )-84 Q 2 HH OCH(CH 3 ) 2 Z
-85 Q2 H F CH3 Z或 E-85 Q 2 HF CH 3 Z or E
-86 Q2 H F C(CH3)3 E 白色固体 (98-10ΓΟ-87 Q2 H F C(CH3)3 Z-86 Q 2 HFC(CH 3 ) 3 E White solid (98-10ΓΟ-87 Q 2 HFC(CH 3 ) 3 Z
-88 Q2 H F / -88 Q 2 HF /
卜 E 白色固体 （ 101-104 °C ) -89 Q2 H F / Z Bu E white solid (101-104 °C) -89 Q 2 HF / Z
CI CI
-90 Q H F H /-90 Q H F H /
2 Z或 E 2 Z or E
-91 Q2 H F Z或 E-91 Q 2 HFZ or E
-92 Q2 H F ) Z或 E-92 Q 2 HF ) Z or E
-93 Q2 H F OCH3 Z或 E-93 Q 2 HF OCH 3 Z or E
-94 Q2 H F OCH2CH3 E 白色固体 ( 101-103 °C)-95 Q2 H F OCH2CH3 Z-94 Q 2 HF OCH 2 CH 3 E White solid (101-103 °C)-95 Q 2 HF OCH 2 CH 3 Z
-96 Q2 H F OCH(CH3)2 E 白色固体 ( 107-110°C)-97 Q2 H F OCH(CH3)2 Z-96 Q 2 HF OCH(CH 3 ) 2 E White solid (107-110°C)-97 Q 2 HF OCH(CH 3 ) 2 Z
-98 Q2 H CI CH3 Z或 E-98 Q 2 H CI CH 3 Z or E
-99 Q2 H CI C(CH3)3 E 白色固体 (112-114°C)-100 Q2 H CI C(CH3)3 Z-99 Q 2 H CI C(CH 3 ) 3 E White solid (112-114 ° C) -100 Q 2 H CI C(CH 3 ) 3 Z
-101 Q2 H CI / Z/E=l:2 白色固体 ( 80-83 °C) -102 Q2 H CI H尸 Z或 E-101 Q 2 H CI / Z/E=l:2 White solid (80-83 °C) -102 Q 2 H CI H corpse Z or E
-103 Q2 H CI M Z或 E-103 Q 2 H CI MZ or E
-104 Q2 H CI K> Z或 E-104 Q 2 H CI K> Z or E
-105 Q2 H CI ) Z或 E-105 Q 2 H CI ) Z or E
-106 Q2 H CI 0CH3 Z或 E-106 Q 2 H CI 0CH3 Z or E
-107 Q2 H CI OCH2CH3 E 黄色固体 （ 76-78 °C)-108 Q2 H CI OCH2CH3 Z-107 Q 2 H CI OCH 2 CH 3 E Yellow solid (76-78 °C)-108 Q 2 H CI OCH 2 CH 3 Z
-109 Q2 H CI OCH(CH3)2 E 白色固体 ( 103-105 °C)-110 Q2 H CI OCH(CH3)2 Z-109 Q 2 H CI OCH(CH 3 ) 2 E White solid (103-105 °C)-110 Q 2 H CI OCH(CH 3 ) 2 Z
-111 Q2 H Br CH3 Z或 E-111 Q 2 H Br CH 3 Z or E
-112 Q2 H Br C(CH3)3 E 白色固体 (108-110°C)-113 Q2 H Br C(CH3)3 Z 白色固体 (113-114°C)-114 Q2 H Br / E 黄色固体 （93-94 °C) -115 Q2 H Br / Z/E=l:3 白色固体 （116-117°C) -112 Q 2 H Br C(CH 3 ) 3 E White solid (108-110 ° C)-113 Q 2 H Br C(CH 3 ) 3 Z White solid (113-114 ° C)-114 Q 2 H Br / E Yellow solid (93-94 °C) -115 Q 2 H Br / Z/E=l:3 White solid (116-117 ° C)
CI CI
-116 Q2 H Br H / Z或 E-116 Q 2 H Br H / Z or E
-117 Q2 H Br Z或 E-117 Q 2 H Br Z or E
-118 Q2 H Br ) Z或 E-118 Q 2 H Br ) Z or E
-119 Q2 H Br 0CH3 Z或 E
Figure imgf000011_0001
Figure imgf000012_0001
-181 Q3 H CI Z或 E-182 Q3 H CI OCH3 Z或 E-183 Q3 H Br CH3 Z或 E-184 Q3 H Br C(CH3)3 Z或 E-185 Q3 H Br / Z或 E -119 Q 2 H Br 0CH3 Z or E
Figure imgf000011_0001
Figure imgf000012_0001
-181 Q 3 H CI Z or E-182 Q 3 H CI OCH 3 Z or E-183 Q 3 H Br CH 3 Z or E-184 Q 3 H Br C(CH 3 ) 3 Z or E-185 Q 3 H Br / Z or E
CI CI
-186 Q3 H Br H / Z或 E-187 Q3 H Br M Z或 E-188 Q3 H Br ) Z或 E-189 Q3 H Br 0CH3 Z或 E-190 Q3 F F CH3 Z或 E-191 Q3 F F C(CH3)3 Z或 E-192 Q3 F F / -186 Q 3 H Br H / Z or E-187 Q 3 H Br MZ or E-188 Q 3 H Br ) Z or E-189 Q 3 H Br 0CH3 Z or E-190 Q 3 FF CH 3 Z or E -191 Q 3 FFC(CH 3 ) 3 Z or E-192 Q 3 FF /
卜 Z或 E -193 Q3 F F H 尸 Z或 E-194 Q3 F F M Z或 E-195 Q3 F F ) Z或 E-196 Q3 F F 0CH3 Z或 E-197 Q3 F CI CH3 Z或 E-198 Q3 F CI C(CH3)3 Z或 E-199 Q3 F CI / Z或 E -200 Q3 F CI H 尸 Z或 E-201 Q3 F CI M Z或 E-202 Q3 F CI 0CH3 Z或 E-203 Q3 F CI OC(CH3)3 Z或 E-204 Q3 CI CI CH3 Z或 E-205 Q3 CI CI C(CH3)3 Z或 E-206 Q3 CI CI / Z或 E Z Z or E -193 Q 3 FFH Corpse Z or E-194 Q 3 FFMZ or E-195 Q 3 FF ) Z or E-196 Q 3 FF 0CH3 Z or E-197 Q 3 F CI CH 3 Z or E- 198 Q 3 F CI C(CH 3 ) 3 Z or E-199 Q 3 F CI / Z or E -200 Q 3 F CI H Corpse Z or E-201 Q 3 F CI MZ or E-202 Q 3 F CI 0CH3 Z or E-203 Q 3 F CI OC(CH 3 ) 3 Z or E-204 Q 3 CI CI CH 3 Z or E-205 Q 3 CI CI C(CH 3 ) 3 Z or E-206 Q 3 CI CI / Z or E
CI CI
-207 Q3 CI CI H / Z或 E-208 Q3 CI CI Z或 E-209 Q3 CI CI ) Z或 E-210 Q3 CI CI 0CH3 Z或 E 部分化合物的 1H NMR (300MHz, CDC13)数据如下： -207 Q 3 CI CI H / Z or E-208 Q 3 CI CI Z or E-209 Q 3 CI CI ) Z or E-210 Q 3 CI CI 0CH3 Z or E The 1H NMR (300MHz, CDC1 3 ) data for some of the compounds are as follows:
化合物 1-2： 7.93 (m, 2H), 7.66 (s, IH), 7.47 (m, 3H), 2.63 (s, 3H), 1.26 (s, 9H)。  Compound 1-2: 7.93 (m, 2H), 7.66 (s, IH), 7.47 (m, 3H), 2.63 (s, 3H), 1.26 (s, 9H).
化合物 1-3： 7.67 (m, 2H), 7.52 (s, IH), 7.41 (m, 3H), 2.19 (s, 3H), 1.33 (s, 9H)。  Compound 1-3: 7.67 (m, 2H), 7.52 (s, IH), 7.41 (m, 3H), 2.19 (s, 3H), 1.33 (s, 9H).
化合物 1-4： 7.94 (m， 2H)， 7.66 (s, IH), 7.47 (m， 3H)， 2.63 (s, 3H)， 1.62 (q， 2H)， 1.21 (s, 6H)， 0.77 (t, 3H) o  Compound 1-4: 7.94 (m, 2H), 7.66 (s, IH), 7.47 (m, 3H), 2.63 (s, 3H), 1.62 (q, 2H), 1.21 (s, 6H), 0.77 (t , 3H) o
化合物 1-10： 7.96 (m, 2H)， 7.75 (s, 1H)， 7.47 (m, 3H)， 4.28 (m, 2H)， 2.60 (s, 3H)， 1.34 (t, Compound 1-10: 7.96 (m, 2H), 7.75 (s, 1H), 7.47 (m, 3H), 4.28 (m, 2H), 2.60 (s, 3H), 1.34 (t,
3H)。 3H).
化合物 1-14： 8.27 (m, 1H)， 7.75 (s, 1H)， 7.44 (m, 1H)， 7.23 (m, 2H)， 2.63 (s, 3H)， 1.26 (s, Compounds 1-14: 8.27 (m, 1H), 7.75 (s, 1H), 7.44 (m, 1H), 7.23 (m, 2H), 2.63 (s, 3H), 1.26 (s,
9H)。 9H).
化合物 1-15： 7.75 (m, 1H)， 7.63 (s, 1H)， 7.42 (m, 1H)， 7.22 (m, 2H)， 2.18 (s, 3H)， 1.37 (s, Compounds 1-15: 7.75 (m, 1H), 7.63 (s, 1H), 7.42 (m, 1H), 7.22 (m, 2H), 2.18 (s, 3H), 1.37 (s,
9H)。 9H).
化合物 1-25： 8.19 (m, 1H)， 7.80 (s, 1H)， 7.51 (m, 1H)， 7.39 (m, 2H)， 2.63 (s, 3H)， 1.22 (s, Compounds 1-25: 8.19 (m, 1H), 7.80 (s, 1H), 7.51 (m, 1H), 7.39 (m, 2H), 2.63 (s, 3H), 1.22 (s,
9H)。 9H).
化合物 1-27： 8.20 (m， IH), 7.80 (s, IH), 7.52 (m， IH), 7.39 (m， 2H)， 2.62 (s, 3H)， 1.59 (q， 2H)， 1.17 (s，6H)， 0.74 (t，3H)。  Compounds 1-27: 8.20 (m, IH), 7.80 (s, IH), 7.52 (m, IH), 7.39 (m, 2H), 2.62 (s, 3H), 1.59 (q, 2H), 1.17 (s , 6H), 0.74 (t, 3H).
化合物 1-34： 8.32 (m， 1H)， 7.89 (s, 1H)， 7.52 (m， 1H)， 7.39 (m， 2H)， 4.89 (hept., 1H)， 2.60 (s, 3H), 1.25 (d, 6H)。  Compound 1-34: 8.32 (m, 1H), 7.89 (s, 1H), 7.52 (m, 1H), 7.39 (m, 2H), 4.89 (hept., 1H), 2.60 (s, 3H), 1.25 ( d, 6H).
化合物 1-37： 8.00 (m, IH), 7.81 (s, IH), 7.71 (m, IH), 7.41 (m, IH), 7.31 (m, IH), 2.62 (s, 3H), 1.20 (s, 9H)。  Compound 1-37: 8.00 (m, IH), 7.81 (s, IH), 7.71 (m, IH), 7.41 (m, IH), 7.31 (m, IH), 2.62 (s, 3H), 1.20 (s , 9H).
化合物 1-38： 7.69 (m, 2H), 7.64 (s, IH), 7.36 (m, IH), 7.26 (m, IH), 2.17 (s, 3H), 1.37 (s, Compound 1-38: 7.69 (m, 2H), 7.64 (s, IH), 7.36 (m, IH), 7.26 (m, IH), 2.17 (s, 3H), 1.37 (s,
9H)。 9H).
化合物 1-56： 7.92 (s, IH), 7.41 (m, IH), 7.35 (m, IH), 7.11 (m, IH), 2.62 (s, 3H), 1.15 (s, Compound 1-56: 7.92 (s, IH), 7.41 (m, IH), 7.35 (m, IH), 7.11 (m, IH), 2.62 (s, 3H), 1.15 (s,
9H)。 9H).
化合物 1-73： 8.04 (m, 3H), 7.48 (m, 3H), 2.60 (s, 3H), 1.36 (s, 9H)。  Compound 1-73: 8.04 (m, 3H), 7.48 (m, 3H), 2.60 (s, 3H), 1.36 (s, 9H).
化合物 1-74: 7.85 (m, 3H), 7.44 (m, 3H), 2.28 (s, 3H), 1.36 (s, 9H)。  Compound 1-74: 7.85 (m, 3H), 7.44 (m, 3H), 2.28 (s, 3H), 1.36 (s, 9H).
化合物 1-75： 8.05 (m, 2H), 8.03 (s, IH), 7.50 (m, 3H), 2.60 (s, 3H), 1.71 (q, 2H), 1.32 (s, 6H), 0.86 (t, 3H)。  Compound 1-75: 8.05 (m, 2H), 8.03 (s, IH), 7.50 (m, 3H), 2.60 (s, 3H), 1.71 (q, 2H), 1.32 (s, 6H), 0.86 (t , 3H).
化合物 1-76： 7.86 (m， 2H)， 7.83 (s, IH), 7.47 (m， 3H)， 2.28 (s, 3H)， 1.73 (q， 2H)， 1.31 (s, 6H)， 0.93 (t, 3H)。  Compound 1-76: 7.86 (m, 2H), 7.83 (s, IH), 7.47 (m, 3H), 2.28 (s, 3H), 1.73 (q, 2H), 1.31 (s, 6H), 0.93 (t , 3H).
化合物 1-81： 8.07 (m, 3H), 7.50 (m, 3H), 4.34 (q, 2H), 2.59 (s, 3H), 1.39 (t, 3H)。  Compound 1-81: 8.07 (m, 3H), 7.50 (m, 3H), 4.34 (q, 2H), 2.59 (s, 3H), 1.39 (t, 3H).
化合物 1-83： 8.07 (m, 2H), 8.07 (s, IH), 7.50 (m, 3H), 4.94 (hept., IH), 2.59 (s, 3H), 1.36 (d, Compound 1-83: 8.07 (m, 2H), 8.07 (s, IH), 7.50 (m, 3H), 4.94 (hept., IH), 2.59 (s, 3H), 1.36 (d,
6H)。 6H).
化合物 1-86： 8.08 (s, IH), 8.03 (m, IH), 7.49 (m, IH), 7.24 (m, 2H), 2.60 (s, 3H), 1.33 (s, Compound 1-86: 8.08 (s, IH), 8.03 (m, IH), 7.49 (m, IH), 7.24 (m, 2H), 2.60 (s, 3H), 1.33 (s,
9H)。 9H).
化合物 1-88： 8.08 (s, IH), 8.04 (m， IH), 7.49 (m， IH), 7.23 (m， 2H)， 2.60 (s, 3H)， 1.68 (q， 2H)， Compound 1-88: 8.08 (s, IH), 8.04 (m, IH), 7.49 (m, IH), 7.23 (m, 2H), 2.60 (s, 3H), 1.68 (q, 2H),
1.29 (s, 6H), 0.83 (t, 3H)。 化合物 1-94: 8.13 (s, 1H)， 8.07 (m, IH), 7.50 (m, 1H)， 7.25 (m, 2H), 4.33 (q, 2H), 2.59 (s, 3H), 1.38 (t, 3H 1.29 (s, 6H), 0.83 (t, 3H). Compound 1-94: 8.13 (s, 1H), 8.07 (m, IH), 7.50 (m, 1H), 7.25 (m, 2H), 4.33 (q, 2H), 2.59 (s, 3H), 1.38 (t , 3H
化合物 1-96： 8.13 (s, 1H)， 8.09 (m， 1H)， 7.50 (m， 1H)， 7.24 (m， 2H)， 4.95 (hept., IH), 2.59 (s, 3H)， 1.35 (d， 6H)。  Compound 1-96: 8.13 (s, 1H), 8.09 (m, 1H), 7.50 (m, 1H), 7.24 (m, 2H), 4.95 (hept., IH), 2.59 (s, 3H), 1.35 ( d, 6H).
化合物 1-99： 8.10 (s, IH), 7.94 (m, IH), 7.52 (m, 1H)， 7.41 (m, 2H), 2.61 (s, 3H), 1.31 (s, Compound 1-99: 8.10 (s, IH), 7.94 (m, IH), 7.52 (m, 1H), 7.41 (m, 2H), 2.61 (s, 3H), 1.31 (s,
9H)。 9H).
化合物 1-107： 8.15 (s, 1H)， 8.03 (m, IH), 7.53 (m， IH), 7.40 (m, 2H), 4.31 (q, 2H), 2.59 (s, 3H), 1.35 (t, 3H  Compound 1-107: 8.15 (s, 1H), 8.03 (m, IH), 7.53 (m, IH), 7.40 (m, 2H), 4.31 (q, 2H), 2.59 (s, 3H), 1.35 (t , 3H
化合物 1-109： 8.14 (s， 1H)， 8.03 (m, 1H)， 7.52 (m， 1H)， 7.41 (m, 2H)， 4.93 (hept., IH), 2.58 (s, 3H), 1.32 (d, 6H  Compound 1-109: 8.14 (s, 1H), 8.03 (m, 1H), 7.52 (m, 1H), 7.41 (m, 2H), 4.93 (hept., IH), 2.58 (s, 3H), 1.32 ( d, 6H
化合物 1-112: 8.10 (s, 1H)， 7.87 (m， 1H)， 7.72 (m， IH), 7.42 (m， 1H)， 7.35 (m， 1H)， 2.60 (s, 3H)， 1.30 (s, 9H)。  Compound 1-112: 8.10 (s, 1H), 7.87 (m, 1H), 7.72 (m, IH), 7.42 (m, 1H), 7.35 (m, 1H), 2.60 (s, 3H), 1.30 (s , 9H).
化合物 1-113： 7.95 (s, IH), 7.82 (m， 1H)， 7.68 (m， IH), 7.40 (m， 1H)， 7.33 (m， IH), 2.28 (s, 3H)， 1.35 (s, 9H)。  Compound 1-113: 7.95 (s, IH), 7.82 (m, 1H), 7.68 (m, IH), 7.40 (m, 1H), 7.33 (m, IH), 2.28 (s, 3H), 1.35 (s , 9H).
化合物 1-114： 8.10 (s, 1H)， 7.86 (m, 1H)， 7.72 (m， IH), 7.38 (m, 2H), 2.60 (s, 3H), 1.66 (q, Compound 1-114: 8.10 (s, 1H), 7.86 (m, 1H), 7.72 (m, IH), 7.38 (m, 2H), 2.60 (s, 3H), 1.66 (q,
2H), 1.26 (s, 6H), 0.81 (t, 3H)。 2H), 1.26 (s, 6H), 0.81 (t, 3H).
化合物 1-120: 8.15 (s, 1H)， 7.97 (m, IH), 7.73 (m, IH), 7.39 (m, 2H), 4.31 (q, 2H), 2.59 (s, 3H), 1.34 (t, 3H)。  Compound 1-120: 8.15 (s, 1H), 7.97 (m, IH), 7.73 (m, IH), 7.39 (m, 2H), 4.31 (q, 2H), 2.59 (s, 3H), 1.34 (t , 3H).
化合物 1-122： 8.15 (s, 1H)， 7.97 (m， 1H)， 7.73 (m， IH), 7.43 (m， 1H)， 7.35 (m， 1H)， 4.93 (hept., IH), 2.59 (s, 3H), 1.32 (d, 6H)。  Compound 1-122: 8.15 (s, 1H), 7.97 (m, 1H), 7.73 (m, IH), 7.43 (m, 1H), 7.35 (m, 1H), 4.93 (hept., IH), 2.59 ( s, 3H), 1.32 (d, 6H).
化合物 1-125： 8.14 (s, 1H)， 7.48 (m, 1H)， 7.07 (m， 2H), 2.60 (s, 3H)， 1.27 (s, 9H  Compound 1-125: 8.14 (s, 1H), 7.48 (m, 1H), 7.07 (m, 2H), 2.60 (s, 3H), 1.27 (s, 9H)
化合物 1-127： 8.14 (s, 1H)， 7.46 (m, IH), 7.06 (m， 2H)， 2.60 (s, 3H), 1.65 (q， 2H)， 1.23 (s, 6H), 0.80 (t, 3H  Compound 1-127: 8.14 (s, 1H), 7.46 (m, IH), 7.06 (m, 2H), 2.60 (s, 3H), 1.65 (q, 2H), 1.23 (s, 6H), 0.80 (t , 3H
化合物 1-132: 8.18 (s, 1H)， 7.49 (m, IH), 7.07 (m, 2H)， 3.94 (s, 3H), 2.59 (s, 3H)。  Compound 1-132: 8.18 (s, 1H), 7.49 (m, IH), 7.07 (m, 2H), 3.94 (s, 3H), 2.59 (s, 3H).
化合物 1-137: 8.18 (s, IH), 7.47 (m, IH), 7.34 (m, IH), 7.17 (m, IH), 2.61 (s, 3H), 1.27 (s, Compound 1-137: 8.18 (s, IH), 7.47 (m, IH), 7.34 (m, IH), 7.17 (m, IH), 2.61 (s, 3H), 1.27 (s,
9H)。 9H).
化合物 1-139： 8.15 (s, 1H)， 7.46 (m， 1H)， 7.34 (m， IH), 7.15 (m， 1H)， 2.60 (s, 3H), 1.63 (q， 2H), 1.22 (s, 6H), 0.78 (t, 3H；)。  Compound 1-139: 8.15 (s, 1H), 7.46 (m, 1H), 7.34 (m, IH), 7.15 (m, 1H), 2.60 (s, 3H), 1.63 (q, 2H), 1.22 (s , 6H), 0.78 (t, 3H;).
化合物 1-145: 8.20 (s, 1H)， 7.45 (m, IH), 7.34 (m， 1H)， 7.12 (m, IH), 6.93 (hept., IH), 2.59 (s, 3H), 1.30 (d, 6H  Compound 1-145: 8.20 (s, 1H), 7.45 (m, IH), 7.34 (m, 1H), 7.12 (m, IH), 6.93 (hept., IH), 2.59 (s, 3H), 1.30 ( d, 6H
化合物 1-148： 8.14 (s, 1H)， 7.43 (m， 3H)， 2.61 (s, 3H)， 1.25 (s, 9H)。  Compound 1-148: 8.14 (s, 1H), 7.43 (m, 3H), 2.61 (s, 3H), 1.25 (s, 9H).
化合物 1-151 : 7.95 (s, IH), 7.39 (m, 3H), 2.26 (s, 3H), 1.72 (q, 2H), 1.30 (s, 6H), 0.93 (t, 3H)。 化合物 1-158： 7.95 (d, 1H)， 7.70 (m， 2H)， 7.48 (m， 2H), 7.35 (m， IH), 6.75 (d, IH), 2.61 (s, 3H)， 1.29 (s, 6H)。  Compound 1-151: 7.95 (s, IH), 7.39 (m, 3H), 2.26 (s, 3H), 1.72 (q, 2H), 1.30 (s, 6H), 0.93 (t, 3H). Compound 1-158: 7.95 (d, 1H), 7.70 (m, 2H), 7.48 (m, 2H), 7.35 (m, IH), 6.75 (d, IH), 2.61 (s, 3H), 1.29 (s , 6H).
化合物 1-160: 7.95 (d, 1H)， 7.71 (m, 2H), 7.47 (m， 2H), 7.36 (m, IH), 6.76 (d, IH), 2.63 (s, Compound 1-160: 7.95 (d, 1H), 7.71 (m, 2H), 7.47 (m, 2H), 7.36 (m, IH), 6.76 (d, IH), 2.63 (s,
3H), 1.65 (q, 2H), 1.24 (s, 6H)， 0.79 (t, 3H)。 化合物 1-165： 7.99 (d, IH), 7.72 (m， 2H)， 7.48 (m， 2H)， 7.36 (m， IH), 6.81 (d, IH), 3.90 (sH), 2.59 (s, 3H)。 3H), 1.65 (q, 2H), 1.24 (s, 6H), 0.79 (t, 3H). Compound 1-165: 7.99 (d, IH), 7.72 (m, 2H), 7.48 (m, 2H), 7.36 (m, IH), 6.81 (d, IH), 3.90 (sH), 2.59 (s, 3H ).
表 2  Table 2
Figure imgf000016_0001
)
Figure imgf000016_0001
)
)
Figure imgf000017_0001
) )
Figure imgf000017_0001
)
Figure imgf000018_0001
-86 H Qi Cl Cl Z或 E
Figure imgf000018_0001
-86 H Qi Cl Cl Z or E
-87 H Qi Cl Cl OCH3 Z或 E-87 H Qi Cl Cl OCH 3 Z or E
-88 H Q2 H H CH3 Z或 E-88 HQ 2 HH CH 3 Z or E
-89 H Q2 H H C(CH3)3 E 紫色固体 （136-137°C )-90 H Q2 H H C(CH3)3 Z 白色固体 （120-li rC )-91 H Q2 H H / -89 HQ 2 HHC(CH 3 ) 3 E Purple solid (136-137 ° C)-90 HQ 2 HHC(CH 3 ) 3 Z White solid (120-li rC )-91 HQ 2 HH /
h E 白色固体 （105-107°C ) -92 H Q2 H H / h E white solid (105-107 ° C) -92 HQ 2 HH /
h Z/E=3:2 黄色固体 ( 101-103 °C ) -93 H Q2 H H H 尸 Z或 Eh Z/E=3:2 yellow solid (101-103 °C) -93 HQ 2 HHH corpse Z or E
-94 H Q2 H H Z或 E-94 HQ 2 HHZ or E
-95 H Q2 H H HO Z或 E-95 HQ 2 HH HO Z or E
-96 H Q2 H H 0CH3 Z或 E-96 HQ 2 HH 0CH3 Z or E
-97 H Q2 H H OCH2CH3 E 黄色固体 （ 118-120 °C )-98 H Q2 H H OCH2CH3 Z 白色固体 （ 76-78 °C )-99 H Q2 H H OCH(CH3)2 E 白色固体 （97-99°C )-100 H Q2 H H OCH(CH3)2 Z-97 HQ 2 HH OCH 2 CH 3 E Yellow solid ( 118-120 ° C )-98 HQ 2 HH OCH 2 CH 3 Z White solid ( 76-78 ° C )-99 HQ 2 HH OCH(CH 3 ) 2 E White solid (97-99 ° C) -100 HQ 2 HH OCH(CH 3 ) 2 Z
-101 H Q2 H F CH3 Z或 E-101 HQ 2 HF CH 3 Z or E
-102 H Q2 H F C(CH3)3 E 白色固体 （146-147°C )-103 H Q2 H F C(CH3)3 Z-102 HQ 2 HFC(CH 3 ) 3 E White solid (146-147°C)-103 HQ 2 HFC(CH 3 ) 3 Z
-104 H Q2 H F / E 白色固体 （101-102°C ) -105 H Q2 H F / -104 HQ 2 HF / E White solid (101-102 ° C) -105 HQ 2 HF /
卜 Z  Bu Z
Cl Cl
-106 H Q2 H F / -106 HQ 2 HF /
h Z或 E h Z or E
-107 H Q2 H F Z或 E-107 HQ 2 HFZ or E
-108 H Q2 H F ) Z或 E-108 HQ 2 HF ) Z or E
-109 H Q2 H F 0CH3 Z或 E-109 HQ 2 HF 0CH3 Z or E
-110 H Q2 H F OCH2CH3 E 白色固体 ( lio-iirc )-111 H Q2 H F OCH2CH3 Z-110 HQ 2 HF OCH 2 CH 3 E White solid ( lio-iirc )-111 HQ 2 HF OCH 2 CH 3 Z
-112 H Q2 H F OCH(CH3)2 E 白色固体 （104-105°C )-113 H Q2 H F OCH(CH3)2 Z-112 HQ 2 HF OCH(CH 3 ) 2 E White solid (104-105 ° C)-113 HQ 2 HF OCH(CH 3 ) 2 Z
-114 H Q2 H Cl CH3 Z或 E-114 HQ 2 H Cl CH 3 Z or E
-115 H Q2 H Cl C(CH3)3 Z/E=l:l 黄色油-116 H Q2 H Cl / E 白色固体 （loo-iorc ) -117 H Q2 H CI / -115 HQ 2 H Cl C(CH 3 ) 3 Z/E=l:l yellow oil-116 HQ 2 H Cl / E white solid (loo-iorc ) -117 HQ 2 H CI /
h z  h z
CI CI
-118 H / -118 H /
Q2 H CI h Z或 EQ 2 H CI h Z or E
-119 H Q2 H CI Z或 E-119 HQ 2 H CI Z or E
-120 H Q2 H CI HO Z或 E-120 HQ 2 H CI HO Z or E
-121 H Q2 H CI OCH3 Z或 E-121 HQ 2 H CI OCH 3 Z or E
-122 H Q2 H CI OCH2CH3 E 白色固体 (116-117°C )-123 H Q2 H CI OCH2CH3 Z-122 HQ 2 H CI OCH 2 CH 3 E White solid (116-117°C)-123 HQ 2 H CI OCH 2 CH 3 Z
-124 H Q2 H CI OCH(CH3)2 E 白色固体 （88-89°C )-125 H Q2 H CI OCH(CH3)2 Z-124 HQ 2 H CI OCH(CH 3 ) 2 E White solid (88-89 ° C) -125 HQ 2 H CI OCH(CH 3 ) 2 Z
-126 H Q2 H Br CH3 Z或 E-126 HQ 2 H Br CH 3 Z or E
-127 H Q2 H Br C(CH3)3 Z/E=l:l 白色固体 ( 103-105 °C )-128 H Q2 H Br / -127 HQ 2 H Br C(CH 3 ) 3 Z/E=l:l White solid (103-105 °C)-128 HQ 2 H Br /
卜 Z/E=4:5 白色固体 （ 90-93 °C ) Bu Z/E=4:5 white solid (90-93 °C)
CICI
-129 H Q2 H Br / -129 HQ 2 H Br /
h Z或 E h Z or E
-130 H Q2 H Br Z或 E-130 HQ 2 H Br Z or E
-131 H Q2 H Br ) Z或 E-131 HQ 2 H Br ) Z or E
-132 H Q2 H Br 0CH3 Z或 E-132 HQ 2 H Br 0CH3 Z or E
-133 H Q2 H Br OCH2CH3 E 白色固体 （116-118°C )-134 H Q2 H Br OCH2CH3 Z-133 HQ 2 H Br OCH 2 CH 3 E White solid (116-118 ° C) -134 HQ 2 H Br OCH 2 CH 3 Z
-135 H Q2 H Br OCH(CH3)2 E 白色固体 （115-116°C )-136 H Q2 H Br OCH(CH3)2 Z-135 HQ 2 H Br OCH(CH 3 ) 2 E White solid (115-116 ° C) -136 HQ 2 H Br OCH(CH 3 ) 2 Z
-137 H Q2 F F CH3 Z或 E-137 HQ 2 FF CH 3 Z or E
-138 H Q2 F F CH(CH3)2 E 黄色油-138 HQ 2 FF CH(CH 3 ) 2 E Yellow oil
-139 H Q2 F F CH(CH3)2 Z-139 HQ 2 FF CH(CH 3 ) 2 Z
-140 H Q2 F F C(CH3)3 E 黄色油-140 HQ 2 FFC(CH 3 ) 3 E Yellow oil
-141 H Q2 F F C(CH3)3 Z/E=l:l 黄色油-141 HQ 2 FFC(CH 3 ) 3 Z/E=l:l yellow oil
-142 H Q2 F F / -142 HQ 2 FF /
卜 E 黄色固体 （ 128-129 °C ) -143 H Q2 F F / Bu E yellow solid (128-129 °C) -143 HQ 2 FF /
卜 Z 白色固体 （130-133°C ) Bu Z white solid (130-133 ° C)
CICI
-144 H Q2 F F / -144 HQ 2 FF /
h E 黄色油  h E yellow oil
CI CI
-145 H Q2 F F / -145 HQ 2 FF /
h Z h Z
-146 H Q2 F F E 黄色油-146 HQ 2 FFE yellow oil
-147 H Q2 F F Z -147 HQ 2 FFZ
Figure imgf000021_0001
-180 H Q2 Cl Cl OCH2CH3 Z
Figure imgf000021_0001
-180 HQ 2 Cl Cl OCH 2 CH 3 Z
-181 H Q2 Cl Cl OCH(CH3)2 E 白色固体 （167-168°C )-182 H Q2 Cl Cl OCH(CH3)2 Z-181 HQ 2 Cl Cl OCH(CH 3 ) 2 E White solid (167-168°C)-182 HQ 2 Cl Cl OCH(CH 3 ) 2 Z
-183 H Q3 H H CH3 Z或 E-183 HQ 3 HH CH 3 Z or E
-184 H Q3 H H C(CH3)3 E 黄色油-185 H Q3 H H C(CH3)3 Z-184 HQ 3 HHC(CH 3 ) 3 E Yellow oil -185 HQ 3 HHC(CH 3 ) 3 Z
-186 H Q3 H H / -186 HQ 3 HH /
卜 E 白色固体 （127°C ) -187 H Q3 H H / Bu E White solid (127 ° C) -187 HQ 3 HH /
卜 Z  Bu Z
Cl Cl
-188 H H / -188 H H /
Q3 H h E 白色固体 (176°C) Q 3 H h E White solid (176°C)
Cl Cl
-189 H Q3 H H / -189 HQ 3 HH /
h Z h Z
-190 H Q3 H H E 黄色油-191 H Q3 H H Z-190 HQ 3 HHE Yellow oil-191 HQ 3 HHZ
-192 H Q3 H H K> E 黄色固体 （100°C )-193 H Q3 H H Z-192 HQ 3 HH K> E Yellow solid (100°C)-193 HQ 3 HHZ
-194 H Q3 H H E 白色固体 （86°C )-195 H Q3 H H Z-194 HQ 3 HHE White solid (86°C)-195 HQ 3 HHZ
-196 H Q3 H H ) E 白色固体 （157°C )-197 H Q3 H H ) Z-196 HQ 3 HH ) E White solid (157°C)-197 HQ 3 HH ) Z
-198 H Q3 H H OCH3 Z/E=l:6 黄色油-199 H Q3 H H OCH2CH3 Z/E=l:2 黄色油-200 H Q3 H H OCH(CH3)2 E 黄色油-201 H Q3 H H OCH(CH3)2 Z 黄色油-202 H Q3 H H OCH2CH(CH3)2 E 黄色油-203 H Q3 H H OCH2CH(CH3)2 Z 黄色油-204 H Q3 H F CH3 Z或 E-198 HQ 3 HH OCH 3 Z/E=l:6 yellow oil-199 HQ 3 HH OCH 2 CH 3 Z/E=l:2 yellow oil-200 HQ 3 HH OCH(CH 3 ) 2 E yellow oil-201 HQ 3 HH OCH(CH 3 ) 2 Z Yellow oil-202 HQ 3 HH OCH 2 CH(CH 3 ) 2 E Yellow oil-203 HQ 3 HH OCH 2 CH(CH 3 ) 2 Z Yellow oil-204 HQ 3 HF CH 3 Z or E
-205 H Q3 H F C(CH3)3 Z或 E-205 HQ 3 HFC(CH 3 ) 3 Z or E
-206 H Q3 H F / -206 HQ 3 HF /
h Z或 E  h Z or E
Cl Cl
-207 H Q3 H F / -207 HQ 3 HF /
h Z或 E h Z or E
-208 H Q3 H F Z或 E-208 HQ 3 HFZ or E
-209 H Q3 H F ) Z或 E-209 HQ 3 HF ) Z or E
-210 H Q3 H F 0CH3 Z或 E-210 HQ 3 HF 0CH3 Z or E
-211 H Q3 H Cl CH3 Z或 E -212 H Q3 H CI C(CH3)3 Z或 E -213 H Q3 H CI / -211 HQ 3 H Cl CH 3 Z or E -212 HQ 3 H CI C(CH 3 ) 3 Z or E -213 HQ 3 H CI /
卜 Z或 E -214 H Q3 H CI H 尸 Z或 E-215 H Q3 H CI Z或 E-216 H Q3 H CI HO Z或 E-217 H Q3 H CI OCH3 Z或 E-218 H Q3 H Br CH3 Z或 E-219 H Q3 H Br C(CH3)3 Z或 E-220 H Q3 H Br / Z Z or E -214 HQ 3 H CI H Corpse Z or E-215 HQ 3 H CI Z or E-216 HQ 3 H CI HO Z or E-217 HQ 3 H CI OCH 3 Z or E-218 HQ 3 H Br CH 3 Z or E-219 HQ 3 H Br C(CH 3 ) 3 Z or E-220 HQ 3 H Br /
卜 Z或 E Bu Z or E
CICI
-221 H / -221 H /
Q3 H Br h Z或 E-222 H Q3 H Br Z或 E-223 H Q3 H Br ) Z或 E-224 H Q3 H Br 0CH3 Z或 E-225 H Q3 F F CH3 Z或 E-226 H Q3 F F C(CH3)3 Z或 E-227 H Q3 F F 卜 / Z或 E -228 H Q3 F F H 尸 Z或 E -229 H Q3 F F Z或 E-230 H Q3 F F HO Z或 E-231 H Q3 F F 0CH3 Z或 E-232 H Q3 F CI CH3 Z或 E-233 H Q3 F CI C(CH3)3 Z或 E-234 H Q3 F CI h / Z或 E Q 3 H Br h Z or E-222 HQ 3 H Br Z or E-223 HQ 3 H Br ) Z or E-224 HQ 3 H Br 0CH3 Z or E-225 HQ 3 FF CH 3 Z or E-226 HQ 3 FFC(CH 3 ) 3 Z or E-227 HQ 3 FF Bu / Z or E -228 HQ 3 FFH Corpse Z or E - 229 HQ 3 FFZ or E-230 HQ 3 FF HO Z or E-231 HQ 3 FF 0CH3 Z or E-232 HQ 3 F CI CH 3 Z or E-233 HQ 3 F CI C(CH 3 ) 3 Z or E-234 HQ 3 F CI h / Z or E
CI CI
-235 H Q I /-235 H Q I /
3 F C h Z或 E-236 H Q3 F CI Z或 E-237 H Q3 F CI ) Z或 E-238 H Q3 F CI OCH3 Z或 E-239 H Q3 CI CI CH3 Z或 E-240 H Q3 CI CI C(CH3)3 Z或 E-241 H Q3 CI CI 卜 / Z或 E
Figure imgf000024_0001
2-274 CI Q2 H CI / 3 FC h Z or E-236 HQ 3 F CI Z or E-237 HQ 3 F CI ) Z or E-238 HQ 3 F CI OCH3 Z or E-239 HQ 3 CI CI CH 3 Z or E-240 HQ 3 CI CI C(CH 3 ) 3 Z or E-241 HQ 3 CI CI Bu / Z or E
Figure imgf000024_0001
2-274 CI Q 2 H CI /
h Z  h Z
CI  CI
2-275 CI Q2 H CI / 2-275 CI Q 2 H CI /
h Z或 E  h Z or E
2-276 CI Q2 H CI Z或 E 2-276 CI Q 2 H CI Z or E
2-277 CI Q2 H CI HO Z或 E 2-277 CI Q 2 H CI HO Z or E
2-278 CI Q2 H CI OCH3 Z或 E 2-278 CI Q 2 H CI OCH 3 Z or E
2-279 CI Q2 H CI OCH2CH3 Z/E=2:3 黄色油 2-279 CI Q 2 H CI OCH 2 CH 3 Z/E=2:3 yellow oil
2-280 CI Q2 H CI OCH(CH3)2 E 黄色固体 （99-lOrC ) 2-280 CI Q 2 H CI OCH(CH 3 ) 2 E Yellow solid (99-lOrC )
2-281 CI Q2 H CI OCH(CH3)2 Z 2-281 CI Q 2 H CI OCH(CH 3 ) 2 Z
2-282 CI Q2 F F CH3 Z或 E 2-282 CI Q 2 FF CH 3 Z or E
2-283 CI Q2 F F C(CH3)3 E 黄色油 2-283 CI Q 2 FFC(CH 3 ) 3 E Yellow oil
2-284 CI Q2 F F C(CH3)3 Z 2-284 CI Q 2 FFC(CH 3 ) 3 Z
2-285 CI Q2 F F / 2-285 CI Q 2 FF /
卜 E 黄色油  Bu E yellow oil
2-286 CI Q2 F F / 2-286 CI Q 2 FF /
h Z  h Z
CI  CI
2-287 CI Q2 F F / 2-287 CI Q 2 FF /
h E 黄色油  h E yellow oil
CI  CI
2-288 CI Q2 F F / 2-288 CI Q 2 FF /
h Z  h Z
2-289 CI Q2 F F Z或 E 2-289 CI Q 2 FFZ or E
2-290 CI Q2 F F ) Z或 E 2-290 CI Q 2 FF ) Z or E
2-291 CI Q2 F F 0CH3 Z或 E 2-291 CI Q 2 FF 0CH3 Z or E
2-292 CI Q2 F F OCH2CH3 E 黄色固体 2-292 CI Q 2 FF OCH 2 CH 3 E Yellow solid
2-293 CI Q2 F F OCH2CH3 Z 2-293 CI Q 2 FF OCH 2 CH 3 Z
2-294 CI Q2 F F OCH(CH3)2 E 白色固体 （115-117°C) 2-294 CI Q 2 FF OCH(CH 3 ) 2 E White solid (115-117 ° C)
2-295 CI Q2 F F OCH(CH3)2 Z 2-295 CI Q 2 FF OCH(CH 3 ) 2 Z
2-296 CI Q2 F F OCH2CH(CH3)2 E 黄色固体 2-296 CI Q 2 FF OCH 2 CH(CH 3 ) 2 E Yellow solid
2-297 CI Q2 F F OCH2CH(CH3)2 Z 2-297 CI Q 2 FF OCH 2 CH(CH 3 ) 2 Z
2-298 CI Q3 H H C(CH3)3 Z或 E 2-298 CI Q 3 HHC(CH 3 ) 3 Z or E
2-299 CI Q3 H H ) Z或 E 2-299 CI Q 3 HH ) Z or E
2-300 CI Q3 H H OCH2CH(CH3)2 Z或 E 2-300 CI Q 3 HH OCH 2 CH(CH 3 ) 2 Z or E
部分化合物的 1H NMR (300MHz, CDC13)数据如下： The 1H NMR (300MHz, CDC1 3 ) data for some of the compounds are as follows:
化合物 2-1： 7.91 (m， 2H), 7.72 (s, IH), 7.49 (m， 3H)， 6.57 (s, IH), 4.24 (q， 2H)， 2.32 (s, 3H) (t, 3H)。 Compound 2-1: 7.91 (m, 2H), 7.72 (s, IH), 7.49 (m, 3H), 6.57 (s, IH), 4.24 (q, 2H), 2.32 (s, 3H) (t, 3H) ).
化合物 2-3： 7.90(m, 2H)， 7.70 (s, 1H)， 7.48 (m， 3H)， 6.54 (s, 1H)， 4.24 (q， 2H)， 2.59 (t， 2H) (s, 3H)， 1.66 (sext, 2H)， 1.49 (t, 3H)， 0.91 (t, 3H)。 化合物 2-5： 7.91 (m， 2H)， 7.68 (s, 1H)， 7.48 (m， 3H), 6.48 (s, IH), 4.26 (q， 2H)， 2.60 (hept., 1H)， 2.32 (s, 3H), 1.51 (t, 3H)， 1.21 (d, 6H)。 Compound 2-3: 7.90 (m, 2H), 7.70 (s, 1H), 7.48 (m, 3H), 6.54 (s, 1H), 4.24 (q, 2H), 2.59 (t, 2H) (s, 3H) ), 1.66 (sext, 2H), 1.49 (t, 3H), 0.91 (t, 3H). Compound 2-5: 7.91 (m, 2H), 7.68 (s, 1H), 7.48 (m, 3H), 6.48 (s, IH), 4.26 (q, 2H), 2.60 (hept., 1H), 2.32 ( s, 3H), 1.51 (t, 3H), 1.21 (d, 6H).
化合物 2-7： 7.94 (m, 2H)， 7.65 (s, IH), 7.46 (m, 3H), 6.37 (s, IH), 4.28 (q, 2H), 2.31 (s, 3H), 1.55 (t, 3H)， 1.25 (s，9H)。  Compound 2-7: 7.94 (m, 2H), 7.65 (s, IH), 7.46 (m, 3H), 6.37 (s, IH), 4.28 (q, 2H), 2.31 (s, 3H), 1.55 (t , 3H), 1.25 (s, 9H).
化合物 2-9： 7.95 (m, 2H)， 7.65 (s, IH), 7.46 (m, 3H), 6.35 (s, IH), 4.28 (q, 2H), 2.32 (s, 3H), Compound 2-9: 7.95 (m, 2H), 7.65 (s, IH), 7.46 (m, 3H), 6.35 (s, IH), 4.28 (q, 2H), 2.32 (s, 3H),
1.59 (q, 2H), 1.55 (t, 3H)， 1.22 (s, 6H), 0.73 (t, 3H)。 1.59 (q, 2H), 1.55 (t, 3H), 1.22 (s, 6H), 0.73 (t, 3H).
化合物 2-10: 7.72 (m， 2H), 7.41 (m, 3H), 7.20 (s, 1H)， 6.18 (s, IH), 3.84 (q, 2H), 2.34 (s, 3H), 1.72 (q, 2H), 1.37 (t, 3H), 1.29 (s, 9H), 0.92 (t, 3H)。  Compound 2-10: 7.72 (m, 2H), 7.41 (m, 3H), 7.20 (s, 1H), 6.18 (s, IH), 3.84 (q, 2H), 2.34 (s, 3H), 1.72 (q , 2H), 1.37 (t, 3H), 1.29 (s, 9H), 0.92 (t, 3H).
化合物 2-11 : 7.93 (m, 2H)， 7.71 (s, IH), 7.47 (m, 3H)， 6.30 (s, IH), 4.28 (q, 2H)， 3.62 (s, 2H), 2.32 (s, 3H), 1.55 (t, 3H), 1.32 (s, 6H)。  Compound 2-11: 7.93 (m, 2H), 7.71 (s, IH), 7.47 (m, 3H), 6.30 (s, IH), 4.28 (q, 2H), 3.62 (s, 2H), 2.32 (s , 3H), 1.55 (t, 3H), 1.32 (s, 6H).
化合物 2-13: 8.01 (m, 2H), 7.71 (s, IH), 7.47 (m, 3H), 6.57 (s, IH), 4.26 (q, 2H), 2.32 (s, 3H), 1.92 (m, IH), 1.48 (t， 3H)， 1.13-1.03 (m, 4H)。  Compound 2-13: 8.01 (m, 2H), 7.71 (s, IH), 7.47 (m, 3H), 6.57 (s, IH), 4.26 (q, 2H), 2.32 (s, 3H), 1.92 (m , IH), 1.48 (t, 3H), 1.13-1.03 (m, 4H).
化合物 2-17： 7.97 (m, 2H)， 7.75 (s, IH), 7.47 (m, 3H)， 6.64 (s, IH), 4.26 (q, 2H)， 3.87 (s, 3H), 2.32 (s, 3H), 1.49 (t, 3H)。  Compound 2-17: 7.97 (m, 2H), 7.75 (s, IH), 7.47 (m, 3H), 6.64 (s, IH), 4.26 (q, 2H), 3.87 (s, 3H), 2.32 (s , 3H), 1.49 (t, 3H).
化合物 2-19： 7.98 (m， 2H)， 7.74 (s, IH), 7.46 (m， 3H), 6.63 (s, IH), 4.28 (q， 2H)， 4.26 (q, 2H), Compounds 2-19: 7.98 (m, 2H), 7.74 (s, IH), 7.46 (m, 3H), 6.63 (s, IH), 4.28 (q, 2H), 4.26 (q, 2H),
2.32 (s, 3H), 1.49 (t, 3H)， 1.32 (t, 3H)。 2.32 (s, 3H), 1.49 (t, 3H), 1.32 (t, 3H).
化合物 2-35: 8.22 (m, 1H)， 7.79 (s, IH), 7.51 (m, IH), 7.40 (m, 2H), 6.38 (s, IH), 4.28 (q， 2H), 2.32 (s, 3H), 1.55 (t, 3H), 1.22 (s, 9H)。  Compound 2-35: 8.22 (m, 1H), 7.79 (s, IH), 7.51 (m, IH), 7.40 (m, 2H), 6.38 (s, IH), 4.28 (q, 2H), 2.32 (s , 3H), 1.55 (t, 3H), 1.22 (s, 9H).
化合物 2-37: 8.24 (m, IH), 7.80 (s, IH), 7.51 (m, IH), 7.39 (m, 2H), 6.35 (s, IH), 4.28 (q, 2H), 2.31 (s, 3H), 1.59 (q, 2H), 1.51 (t, 3H), 1.17 (s, 6H), 0.72 (t, 3H)。  Compound 2-37: 8.24 (m, IH), 7.80 (s, IH), 7.51 (m, IH), 7.39 (m, 2H), 6.35 (s, IH), 4.28 (q, 2H), 2.31 (s , 3H), 1.59 (q, 2H), 1.51 (t, 3H), 1.17 (s, 6H), 0.72 (t, 3H).
化合物 2-43: 8.33 (m， 1H)， 7.89 (s, IH), 7.52 (m， 1H)， 7.40 (m, 2H), 6.63 (s, 1H)， 4.28 (q, 2H), 4.25 (q, 2H), 2.33 (s, 3H), 1.49 (t, 3H), 1.27 (t, 3H)。  Compound 2-43: 8.33 (m, 1H), 7.89 (s, IH), 7.52 (m, 1H), 7.40 (m, 2H), 6.63 (s, 1H), 4.28 (q, 2H), 4.25 (q , 2H), 2.33 (s, 3H), 1.49 (t, 3H), 1.27 (t, 3H).
化合物 2-58： 7.87 (s, 1H)， 7.44 (m, 1H)， 7.06 (m， 2H)， 6.40 (s, 1H)， 4.26 (q， 2H)， 2.31 (s, 3H), 1.53 (t, 3H), 1.19 (s, 9H) o  Compound 2-58: 7.87 (s, 1H), 7.44 (m, 1H), 7.06 (m, 2H), 6.40 (s, 1H), 4.26 (q, 2H), 2.31 (s, 3H), 1.53 (t , 3H), 1.19 (s, 9H) o
化合物 2-66： 7.94 (s, IH), 7.43 (m, IH), 7.07 (m, 2H), 6.63 (s, IH), 4.26 (q, 2H), 4.25 (q, 2H), Compound 2-66: 7.94 (s, IH), 7.43 (m, IH), 7.07 (m, 2H), 6.63 (s, IH), 4.26 (q, 2H), 4.25 (q, 2H),
2.32 (s, 3H)， 1.47 (t, 3H)， 1.28 (t, 3H)。 2.32 (s, 3H), 1.47 (t, 3H), 1.28 (t, 3H).
化合物 2-68： 7.93 (s, 1H)， 7.43 (m， 1H)， 7.06 (m， 2H)， 6.63 (s, 1H)， 4.89 (hept., 1H)， 4.24 (q， 2H), 2.32 (s, 3H)， 1.47 (t, 3H)， 1.24 (d, 6H)。  Compound 2-68: 7.93 (s, 1H), 7.43 (m, 1H), 7.06 (m, 2H), 6.63 (s, 1H), 4.89 (hept., 1H), 4.24 (q, 2H), 2.32 ( s, 3H), 1.47 (t, 3H), 1.24 (d, 6H).
化合物 2-71 : 7.91 (s, 1H), 7.41 (m, IH), 7.35 (m， lH)，7.14 (m, IH), 6.42 (s, 1H)， 4.25 (q, 2H), 2.31 (s, 3H), 1.51 (t, 3H)， 1.15 (s, 9H)。  Compound 2-71: 7.91 (s, 1H), 7.41 (m, IH), 7.35 (m, lH), 7.14 (m, IH), 6.42 (s, 1H), 4.25 (q, 2H), 2.31 (s , 3H), 1.51 (t, 3H), 1.15 (s, 9H).
化合物 2-73: 7.91 (s, 1H)， 7.42 (m， 1H)， 7.35 (m， 1H)， 7.11 (m， 1H)， 6.39 (s, 1H)， 4.26 (q, 2H)， 2.30 (s， 3H)， 1.62 (q， 2H)， 1.50 (t, 3H), 1.11 (s, 6H)， 0.65 (t, 3H)。  Compound 2-73: 7.91 (s, 1H), 7.42 (m, 1H), 7.35 (m, 1H), 7.11 (m, 1H), 6.39 (s, 1H), 4.26 (q, 2H), 2.30 (s , 3H), 1.62 (q, 2H), 1.50 (t, 3H), 1.11 (s, 6H), 0.65 (t, 3H).
化合物 2-89： 8.04 (m, 2H)， 8.02 (s, IH), 7.49 (m, 3H), 6.37 (s, IH), 4.25 (q, 2H), 2.31 (s, 3H), 1.53 (t, 3H)， 1.35 (s，9H)。  Compound 2-89: 8.04 (m, 2H), 8.02 (s, IH), 7.49 (m, 3H), 6.37 (s, IH), 4.25 (q, 2H), 2.31 (s, 3H), 1.53 (t , 3H), 1.35 (s, 9H).
化合物 2-90： 7.92 (m， 2H), 7.45 (m, 3H), 7.39 (s, 1H)， 6.18 (s, IH), 3.93 (q, 2H)， 2.33 (s, 3H), Compound 2-90: 7.92 (m, 2H), 7.45 (m, 3H), 7.39 (s, 1H), 6.18 (s, IH), 3.93 (q, 2H), 2.33 (s, 3H),
1.36 (t, 3H), 1.34 (s，9H)。 化合物 2-91： 8.05 (m, 2H), 8.02 (s, 1H)， 7.50 (m， 3H)， 6.34 (s, IH), 4.25 (q， 2H)， 2.30 (s, 3H), 1.68 (q， 2H)， 1.53 (t, 3H), 1.30 (s, 6H)， 0.81 (t, 3H)。 1.36 (t, 3H), 1.34 (s, 9H). Compound 2-91: 8.05 (m, 2H), 8.02 (s, 1H), 7.50 (m, 3H), 6.34 (s, IH), 4.25 (q, 2H), 2.30 (s, 3H), 1.68 (q , 2H), 1.53 (t, 3H), 1.30 (s, 6H), 0.81 (t, 3H).
化合物 2-97： 8.07 (m， 2H)， 8.06 (s, 1H)， 7.49 (m， 3H)， 6.61 (s, 1H)， 4.32 (q， 2H)， 4.24 (q， 2H)， 2.32 (s, 3H)， 1.48 (t, 3H), 1.37 (t, 3H)。  Compound 2-97: 8.07 (m, 2H), 8.06 (s, 1H), 7.49 (m, 3H), 6.61 (s, 1H), 4.32 (q, 2H), 4.24 (q, 2H), 2.32 (s , 3H), 1.48 (t, 3H), 1.37 (t, 3H).
化合物 2-98： 7.91 (m, 2H), 7.45 (m， 3H)， 7.45 (s, 1H)， 6.27 (s, IH), 4.30 (q， 2H)， 3.95 (q, 2H), Compound 2-98: 7.91 (m, 2H), 7.45 (m, 3H), 7.45 (s, 1H), 6.27 (s, IH), 4.30 (q, 2H), 3.95 (q, 2H),
2.34 (s, 3H), 1.37 (t， 3H), 1.36 (t, 3H)。 2.34 (s, 3H), 1.37 (t, 3H), 1.36 (t, 3H).
化合物 2-99： 8.08 (m, 2H)， 8.07 (s, 1H)， 7.49 (m， 3H)， 6.62 (s, IH), 4.94 (hept., 1H)， 4.24 (q, 2H), 2.32 (s, 3H)， 1.48 (t, 3H), 1.35 (d， 6H)。  Compound 2-99: 8.08 (m, 2H), 8.07 (s, 1H), 7.49 (m, 3H), 6.62 (s, IH), 4.94 (hept., 1H), 4.24 (q, 2H), 2.32 ( s, 3H), 1.48 (t, 3H), 1.35 (d, 6H).
化合物 2-102： 8.08 (s, IH), 8.04 (m， IH), 7.47 (m， IH), 7.23 (m， 2H)， 6.37 (s, IH), 4.25 (q， 2H), 2.31 (s, 3H)， 1.53 (t, 3H)， 1.32 (s, 9H)。  Compound 2-102: 8.08 (s, IH), 8.04 (m, IH), 7.47 (m, IH), 7.23 (m, 2H), 6.37 (s, IH), 4.25 (q, 2H), 2.31 (s , 3H), 1.53 (t, 3H), 1.32 (s, 9H).
化合物 2-104： 8.08 (s, 1H)， 8.07 (m， IH), 7.46 (m， 1H)， 7.25 (m， 2H), 6.34 (s, 1H)， 4.25 (q, 2H), 2.30 (s, 3H)， 1.66 (q, 2H), 1.53 (t, 3H)， 1.28 (s, 6H), 0.79 (t, 3H；)。  Compound 2-104: 8.08 (s, 1H), 8.07 (m, IH), 7.46 (m, 1H), 7.25 (m, 2H), 6.34 (s, 1H), 4.25 (q, 2H), 2.30 (s , 3H), 1.66 (q, 2H), 1.53 (t, 3H), 1.28 (s, 6H), 0.79 (t, 3H;).
化合物 2-110: 8.12 (s, 1H)， 8.08 (m, IH), 7.50 (m， 1H)， 7.25 (m， 2H), 6.39 (s, 1H)， 4.32 (q, 2H), 4.25 (q， 2H)， 2.32 (s, 3H), 1.47 (t, 3H)， 1.37 (t, 3H)。  Compound 2-110: 8.12 (s, 1H), 8.08 (m, IH), 7.50 (m, 1H), 7.25 (m, 2H), 6.39 (s, 1H), 4.32 (q, 2H), 4.25 (q , 2H), 2.32 (s, 3H), 1.47 (t, 3H), 1.37 (t, 3H).
化合物 2-112： 8.12 (s, 1H)， 8.08 (m， 1H)， 7.49 (m， 1H)， 7.24 (m， 2H)， 6.38 (s, 1H)， 4.93 (hept., Compound 2-112: 8.12 (s, 1H), 8.08 (m, 1H), 7.49 (m, 1H), 7.24 (m, 2H), 6.38 (s, 1H), 4.93 (hept.,
IH), 4.24 (q， 2H)， 2.32 (s, 3H)， 1.48 (t， 3H)， 1.27 (d， 6H)。 IH), 4.24 (q, 2H), 2.32 (s, 3H), 1.48 (t, 3H), 1.27 (d, 6H).
化合物 2-116： 8.10 (s, 1H)， 7.95 (m， 1H)， 7.51 (m， 1H)， 7.40 (m， 2H), 6.34 (s, 1H)， 4.25 (q, 2H), 2.30 (s, 3H)， 1.65 (q, 2H), 1.53 (t, 3H)， 1.26 (s, 6H), 0.78 (t, 3H；)。  Compound 2-116: 8.10 (s, 1H), 7.95 (m, 1H), 7.51 (m, 1H), 7.40 (m, 2H), 6.34 (s, 1H), 4.25 (q, 2H), 2.30 (s , 3H), 1.65 (q, 2H), 1.53 (t, 3H), 1.26 (s, 6H), 0.78 (t, 3H;).
化合物 2-122： 8.15 (s, IH), 8.03 (m， IH), 7.51 (m， 1H)， 7.39 (m， 2H), 6.61 (s, 1H)， 4.29 (q, 2H), 4.24 (q, 2H), 2.32 (s, 3H), 1.48 (t, 3H), 1.33 (t, 3H) o  Compound 2-122: 8.15 (s, IH), 8.03 (m, IH), 7.51 (m, 1H), 7.39 (m, 2H), 6.61 (s, 1H), 4.29 (q, 2H), 4.24 (q , 2H), 2.32 (s, 3H), 1.48 (t, 3H), 1.33 (t, 3H) o
化合物 2-124： 8.15 (s, 1H)， 8.05 (m， 1H)， 7.53 (m， 1H)， 7.40 (m， 2H)， 6.61 (s, 1H)， 4.90 (hept., IH), 4.24 (q, 2H), 2.32 (s, 3H), 1.48 (t, 3H), 1.31 (d, 6H)。  Compound 2-124: 8.15 (s, 1H), 8.05 (m, 1H), 7.53 (m, 1H), 7.40 (m, 2H), 6.61 (s, 1H), 4.90 (hept., IH), 4.24 ( q, 2H), 2.32 (s, 3H), 1.48 (t, 3H), 1.31 (d, 6H).
化合物 2-133： 8.16 (s, 1H)， 7.98 (m， 1H)， 7.74 (m， 1H)， 7.73 (m， IH), 7.35 (m， 1H)， 6.36 (s, IH), 4.29 (q, 2H), 4.24 (q, 2H), 2.32 (s, 3H)， 1.48 (t, 3H), 1.33 (t, 3H) o  Compound 2-133: 8.16 (s, 1H), 7.98 (m, 1H), 7.74 (m, 1H), 7.73 (m, IH), 7.35 (m, 1H), 6.36 (s, IH), 4.29 (q , 2H), 4.24 (q, 2H), 2.32 (s, 3H), 1.48 (t, 3H), 1.33 (t, 3H) o
化合物 2-135: 8.15 (s, IH), 7.97 (m， 1H)， 7.73 (m, IH), 7.43 (m， IH), 7.34 (m, 1H)， 6.37 (s, Compound 2-135: 8.15 (s, IH), 7.97 (m, 1H), 7.73 (m, IH), 7.43 (m, IH), 7.34 (m, 1H), 6.37 (s,
IH), 4.92 (hept., 1H)， 4.24 (q, 2H), 2.32 (s, 3H), 1.48 (t, 3H), 1.30 (d, 6H)。 IH), 4.92 (hept., 1H), 4.24 (q, 2H), 2.32 (s, 3H), 1.48 (t, 3H), 1.30 (d, 6H).
化合物 2-138： 8.13 (s, IH), 7.46 (m， IH), 7.07 (m， 2H)， 6.49 (s, IH), 4.24 (q， 2H)， 2.90 (hept., IH), 2.31 (s, 3H)， 1.49 (t, 3H)， 1.25 (d， 6H)。  Compound 2-138: 8.13 (s, IH), 7.46 (m, IH), 7.07 (m, 2H), 6.49 (s, IH), 4.24 (q, 2H), 2.90 (hept., IH), 2.31 ( s, 3H), 1.49 (t, 3H), 1.25 (d, 6H).
化合物 2-140： 8.13 (s, 1H)， 7.48 (m， IH), 7.07 (m， 2H)， 6.39 (s, IH), 4.25 (q， 2H)， 2.31 (s, 3H), 1.52 (t, 3H)， 1.29 (s, 9H)。  Compound 2-140: 8.13 (s, 1H), 7.48 (m, IH), 7.07 (m, 2H), 6.39 (s, IH), 4.25 (q, 2H), 2.31 (s, 3H), 1.52 (t , 3H), 1.29 (s, 9H).
化合物 2-142： 8.13 (s, 1H)， 7.49 (m， 1H)， 7.06 (m, 2H)， 6.36 (s, IH), 4.25 (q， 2H)， 2.30 (s, 3H), 1.64 (q， 2H)， 1.52 (t, 3H), 1.25 (s, 6H)， 0.76 (t, 3H)。  Compound 2-142: 8.13 (s, 1H), 7.49 (m, 1H), 7.06 (m, 2H), 6.36 (s, IH), 4.25 (q, 2H), 2.30 (s, 3H), 1.64 (q , 2H), 1.52 (t, 3H), 1.25 (s, 6H), 0.76 (t, 3H).
化合物 2-143： 7.47 (s, 1H)， 7.44 (m， 1H)， 7.01 (m， 2H)， 6.19 (s, IH), 3.93 (q， 2H)， 2.31 (s, 3H), 1.71 (q， 2H)， 1.36 (t, 3H)， 1.28 (s, 6H)， 0.90 (t, 3H)。  Compound 2-143: 7.47 (s, 1H), 7.44 (m, 1H), 7.01 (m, 2H), 6.19 (s, IH), 3.93 (q, 2H), 2.31 (s, 3H), 1.71 (q , 2H), 1.36 (t, 3H), 1.28 (s, 6H), 0.90 (t, 3H).
化合物 2-144： 8.19 (s, 1H)， 7.51 (m， 1H)， 7.08 (m， 2H)， 6.40 (s, IH), 4.25 (q， 2H)， 3.69 (s, 2H), Compound 2-144: 8.19 (s, 1H), 7.51 (m, 1H), 7.08 (m, 2H), 6.40 (s, IH), 4.25 (q, 2H), 3.69 (s, 2H),
2.31 (s, 3H)， 1.52 (t, 3H), 1.37 (s, 6H)。 化合物 2-146: 8.15 (s, IH), 7.44 (m, 1H)， 7.07 (m, 2H), 6.56 (s, IH), 4.24 (q, 2H), 2.31 (s， 3H)， 1.94 (m, IH), 1.49 (t, 3H), 1.14 (m, 2H), 1.06 (m, 2H)。 2.31 (s, 3H), 1.52 (t, 3H), 1.37 (s, 6H). Compound 2-146: 8.15 (s, IH), 7.44 (m, 1H), 7.07 (m, 2H), 6.56 (s, IH), 4.24 (q, 2H), 2.31 (s, 3H), 1.94 (m , IH), 1.49 (t, 3H), 1.14 (m, 2H), 1.06 (m, 2H).
化合物 2-148： 8.11 (s, 1H)， 7.46 (m， 1H)， 7.07 (m， 2H)， 6.53 (s, IH), 4.23 (q， 2H)， 3.33 (m， 1H)， 2.33 (m， 2H)， 2.31 (s, 3H)， 1.96 (m， 2H)， 1.47 (t, 3H)。  Compound 2-148: 8.11 (s, 1H), 7.46 (m, 1H), 7.07 (m, 2H), 6.53 (s, IH), 4.23 (q, 2H), 3.33 (m, 1H), 2.33 (m , 2H), 2.31 (s, 3H), 1.96 (m, 2H), 1.47 (t, 3H).
化合物 2-150： 8.13 (s, IH), 7.46 (m， IH), 7.07 (m, 2H), 6.49 (s, IH), 4.24 (q, 2H), 2.92 (m， Compound 2-150: 8.13 (s, IH), 7.46 (m, IH), 7.07 (m, 2H), 6.49 (s, IH), 4.24 (q, 2H), 2.92 (m,
1H)， 2.31 (s, 3H), 1.94-1.59 (m， 8H)， 1.48 (t, 3H)。 1H), 2.31 (s, 3H), 1.94-1.59 (m, 8H), 1.48 (t, 3H).
化合物 2-152: 8.18 (s, IH), 7.47 (m, IH), 7.07 (m, 2H), 6.63 (s, IH), 4.24 (q, 2H), 3.92 (s, 2H)， 2.31 (s, 3H)， 1.46 (t, 3H)。  Compound 2-152: 8.18 (s, IH), 7.47 (m, IH), 7.07 (m, 2H), 6.63 (s, IH), 4.24 (q, 2H), 3.92 (s, 2H), 2.31 (s , 3H), 1.46 (t, 3H).
化合物 2-154： 8.18 (s, 1H)， 7.45 (m， 1H)， 7.06 (m， 2H)， 6.62 (s, 1H)， 4.32 (q， 2H)， 4.25 (q， 2H), 2.31 (s, 3H)， 1.47 (t, 3H)， 1.34 (t, 3H)。  Compound 2-154: 8.18 (s, 1H), 7.45 (m, 1H), 7.06 (m, 2H), 6.62 (s, 1H), 4.32 (q, 2H), 4.25 (q, 2H), 2.31 (s , 3H), 1.47 (t, 3H), 1.34 (t, 3H).
化合物 2-156： 8.18 (s, IH), 7.48 (m， 1H)， 7.06 (m, 2H), 6.62 (s, 1H)， 4.93 (hept., 1H)， 4.24 (q, 2H), 2.31 (s, 3H), 1.47 (t, 3H), 1.31 (d， 6H)。  Compound 2-156: 8.18 (s, IH), 7.48 (m, 1H), 7.06 (m, 2H), 6.62 (s, 1H), 4.93 (hept., 1H), 4.24 (q, 2H), 2.31 ( s, 3H), 1.47 (t, 3H), 1.31 (d, 6H).
化合物 2-160： 8.21 (s， 1H)， 7.45 (m， 1H)， 7.34 (m， 1H)， 7.15 (m， IH), 6.62 (s, 1H)， 4.30 (q， 2H)， 4.27 (q， 2H)， 2.32 (s， 3H)， 1.47 (t, 3H)， 1.30 (t, 3H)。  Compound 2-160: 8.21 (s, 1H), 7.45 (m, 1H), 7.34 (m, 1H), 7.15 (m, IH), 6.62 (s, 1H), 4.30 (q, 2H), 4.27 (q , 2H), 2.32 (s, 3H), 1.47 (t, 3H), 1.30 (t, 3H).
化合物 2-168： 8.20 (s, 1H)， 7.43 (m， 1H)， 7.34 (m， 1H)， 7.14 (m， 1H)， 6.61 (s, 1H)， 4.93 (hept., Compound 2-168: 8.20 (s, 1H), 7.43 (m, 1H), 7.34 (m, 1H), 7.14 (m, 1H), 6.61 (s, 1H), 4.93 (hept.,
IH), 4.24 (q， 2H)， 2.32 (s, 3H)， 1.47 (t, 3H)， 1.28 (d， 6H)。 IH), 4.24 (q, 2H), 2.32 (s, 3H), 1.47 (t, 3H), 1.28 (d, 6H).
化合物 2-172： 7.39 (m, 3H), 7.38 (s, 1H)， 6.20 (s, IH), 3.94 (q, 2H), 2.29 (s, 3H), 1.37 (t, 3H)， 1.34 (s, 9H)。  Compound 2-172: 7.39 (m, 3H), 7.38 (s, 1H), 6.20 (s, IH), 3.94 (q, 2H), 2.29 (s, 3H), 1.37 (t, 3H), 1.34 (s , 9H).
化合物 2-173： 8.13 (s, 1H)， 7.43 (m， 3H), 6.37 (s, 1H)， 4.25 (q， 2H)， 2.30 (s, 3H), 1.61 (q， 2H)， 1.53 (t, 3H)， 1.21 (s, 6H), 0.74 (t, 3H)。  Compound 2-173: 8.13 (s, 1H), 7.43 (m, 3H), 6.37 (s, 1H), 4.25 (q, 2H), 2.30 (s, 3H), 1.61 (q, 2H), 1.53 (t , 3H), 1.21 (s, 6H), 0.74 (t, 3H).
化合物 2-174： 7.38 (m， 3H)， 7.38 (s, 1H)， 6.20 (s, 1H)， 3.94 (q， 2H)， 2.29 (s, 3H)， 1.71 (q， 2H)， 1.37 (t, 3H)， 1.29 (s, 6H)， 0.90 (t, 3H)。  Compound 2-174: 7.38 (m, 3H), 7.38 (s, 1H), 6.20 (s, 1H), 3.94 (q, 2H), 2.29 (s, 3H), 1.71 (q, 2H), 1.37 (t , 3H), 1.29 (s, 6H), 0.90 (t, 3H).
化合物 2-179： 8.20 (s, 1H)， 7.44 (m， 3H)， 6.61 (s, 1H)， 4.28 (q， 2H)， 4.24 (q， 2H)， 2.31 (s, 3H)， 1.48 (t, 3H)， 1.28 (t, 3H)。  Compound 2-179: 8.20 (s, 1H), 7.44 (m, 3H), 6.61 (s, 1H), 4.28 (q, 2H), 4.24 (q, 2H), 2.31 (s, 3H), 1.48 (t , 3H), 1.28 (t, 3H).
化合物 2-181： 8.19 (s, 1H)， 7.43 (m, 3H), 6.62 (s, 1H)， 4.92 (hept., IH), 4.24 (q， 2H)， 2.31 (s, Compound 2-181: 8.19 (s, 1H), 7.43 (m, 3H), 6.62 (s, 1H), 4.92 (hept., IH), 4.24 (q, 2H), 2.31 (s,
3H), 1.48 (t, 3H)， 1.26 (d, 6H)。 3H), 1.48 (t, 3H), 1.26 (d, 6H).
化合物 2-184: 7.95 (d, IH), 7.71 (m, 2H)， 7.48 (m, 2H), 7.35 (m, IH), 6.76 (d, IH), 6.35 (s, IH), 4.26 (q， 2H)， 2.31 (s, 3H)， 1.54 (t， 3H)， 1.28 (s, 9H)。  Compound 2-184: 7.95 (d, IH), 7.71 (m, 2H), 7.48 (m, 2H), 7.35 (m, IH), 6.76 (d, IH), 6.35 (s, IH), 4.26 (q , 2H), 2.31 (s, 3H), 1.54 (t, 3H), 1.28 (s, 9H).
化合物 2-186: 7.95 (d, 1H)， 7.71 (m， 2H), 7.47 (m， 2H)， 7.36 (m， IH), 6.76 (d， 1H)， 6.33 (s, IH), 4.26 (q, 2H)， 2.30 (s, 3H), 1.63 (q, 2H)， 1.54 (t, 3H), 1.19 (s, 6H)， 0.76 (t, 3H)。  Compound 2-186: 7.95 (d, 1H), 7.71 (m, 2H), 7.47 (m, 2H), 7.36 (m, IH), 6.76 (d, 1H), 6.33 (s, IH), 4.26 (q , 2H), 2.30 (s, 3H), 1.63 (q, 2H), 1.54 (t, 3H), 1.19 (s, 6H), 0.76 (t, 3H).
化合物 2-188： 7.95 (d, IH), 7.69 (m， 2H), 7.48 (m, 2H), 7.34 (m， IH), 6.81 (d, 1H)， 6.35 (s, 1H)， 4.27 (q， 2H), 3.65 (s, 2H), 2.31 (s, 3H), 1.54 (t, 3H), 1.35 (s, 6H)。  Compound 2-188: 7.95 (d, IH), 7.69 (m, 2H), 7.48 (m, 2H), 7.34 (m, IH), 6.81 (d, 1H), 6.35 (s, 1H), 4.27 (q , 2H), 3.65 (s, 2H), 2.31 (s, 3H), 1.54 (t, 3H), 1.35 (s, 6H).
化合物 2-190： 7.96 (d, IH), 7.71 (m， 2H), 7.46 (m， 2H)， 7.34 (m， IH), 6.77 (d, IH), 6.33 (s, IH), 4.26 (q, 2H), 2.32 (s, 3H), 1.92 (m, IH), 1.48 (t, 3H), 1.13-1.03 (m, 4H)。  Compound 2-190: 7.96 (d, IH), 7.71 (m, 2H), 7.46 (m, 2H), 7.34 (m, IH), 6.77 (d, IH), 6.33 (s, IH), 4.26 (q , 2H), 2.32 (s, 3H), 1.92 (m, IH), 1.48 (t, 3H), 1.13-1.03 (m, 4H).
化合物 2-192: 7.94 (d, IH), 7.68 (m, 2H)， 7.47 (m, 2H), 7.35 (m, IH), 6.74 (d, IH), 6.50 (s, Compound 2-192: 7.94 (d, IH), 7.68 (m, 2H), 7.47 (m, 2H), 7.35 (m, IH), 6.74 (d, IH), 6.50 (s,
IH), 4.23 (q, 2H)， 3.40 (pent., IH), 2.31 (s, 3H), 2.45-2.25 (m, 2H)， 2.10-1.92 (m, 2H), 1.49 (t, 3H)。 (I, H. 3H).
化合物 2-194： 7.95 (d, IH), 7.70 (m， 2H)， 7.47 (m， 2H)， 7.35 (m， IH), 6.76 (d, IH), 6.46 (s, IH), 4.25 (q， 2H)， 3.01 (pent., 1H)， 2.33 (s, 3H)， 1.96-1.85 (m, 4H)， 1.69-1.58 (m, 4H)， 1.50 (t, 3H)。  Compound 2-194: 7.95 (d, IH), 7.70 (m, 2H), 7.47 (m, 2H), 7.35 (m, IH), 6.76 (d, IH), 6.46 (s, IH), 4.25 (q , 2H), 3.01 (pent., 1H), 2.33 (s, 3H), 1.96-1.85 (m, 4H), 1.69-1.58 (m, 4H), 1.50 (t, 3H).
化合物 2-196： 7.95 (d, IH), 7.68 (m， 2H)， 7.46 (m， 2H)， 7.35 (m， IH), 6.76 (d, IH), 6.45 (s, Compound 2-196: 7.95 (d, IH), 7.68 (m, 2H), 7.46 (m, 2H), 7.35 (m, IH), 6.76 (d, IH), 6.45 (s,
IH), 4.25 (q， 2H)， 2.58 (m, IH), 2.31 (s, 3H)， 2.08-1.95 (m, 2H)， 1.77-1.70 (m, 4H)， 1.50 (t， 3H)， 1.52-1.48 (m, 2H)， 1.33-1.28 (m, 2H)。 IH), 4.25 (q, 2H), 2.58 (m, IH), 2.31 (s, 3H), 2.08-1.95 (m, 2H), 1.77-1.70 (m, 4H), 1.50 (t, 3H), 1.52 -1.48 (m, 2H), 1.33-1.28 (m, 2H).
化合物 2-200： 7.98 (d, IH), 7.74 (m， 2H)， 7.47 (m， 2H)， 7.38 (m， IH), 6.82 (d, IH), 6.61 (s, IH), 4.91 (pent., IH), 4.24 (q， 2H)， 2.32 (s, 3H)， 1.48 (t, 3H)， 1.29 (d, 6H)。  Compound 2-200: 7.98 (d, IH), 7.74 (m, 2H), 7.47 (m, 2H), 7.38 (m, IH), 6.82 (d, IH), 6.61 (s, IH), 4.91 (pent) ., IH), 4.24 (q, 2H), 2.32 (s, 3H), 1.48 (t, 3H), 1.29 (d, 6H).
化合物 2-201： 7.81 (d, IH), 7.63 (m， 2H)， 7.44 (m， 2H)， 7.33 (m， IH), 6.29 (s, IH), 5.81 (d, Compound 2-201: 7.81 (d, IH), 7.63 (m, 2H), 7.44 (m, 2H), 7.33 (m, IH), 6.29 (s, IH), 5.81 (d,
IH), 4.92 (hept., 1H)， 3.90 (q， 2H)， 2.33 (s, 3H)， 1.48 (t， 3H)， 1.33 (d, 6H)。 IH), 4.92 (hept., 1H), 3.90 (q, 2H), 2.33 (s, 3H), 1.48 (t, 3H), 1.33 (d, 6H).
化合物 2-202： 7.99 (d, IH), 7.72 (m， 2H)， 7.47 (m， 2H)， 7.38 (m， IH), 6.83 (d, IH), 6.61 (s, IH), 4.26 (q， 2H)， 3.99 (d, 2H)， 2.32 (s, 3H)， 2.01 (hept., 1H)， 1.48 (t， 3H)， 0.92 (d， 6H)。  Compound 2-202: 7.99 (d, IH), 7.72 (m, 2H), 7.47 (m, 2H), 7.38 (m, IH), 6.83 (d, IH), 6.61 (s, IH), 4.26 (q , 2H), 3.99 (d, 2H), 2.32 (s, 3H), 2.01 (hept., 1H), 1.48 (t, 3H), 0.92 (d, 6H).
化合物 2-203： 7.81 (d, IH), 7.64 (m， 2H)， 7.45 (m， 2H)， 7.35 (m， IH), 6.29 (s, IH), 5.81 (d, 1H)， 4.02 (d， 2H)， 3.90 (q， 2H)， 2.33 (s, 3H)， 2.08 (hept., 1H)， 1.32 (t， 3H)， 0.97 (d， 6H)。  Compound 2-203: 7.81 (d, IH), 7.64 (m, 2H), 7.45 (m, 2H), 7.35 (m, IH), 6.29 (s, IH), 5.81 (d, 1H), 4.02 (d , 2H), 3.90 (q, 2H), 2.33 (s, 3H), 2.08 (hept., 1H), 1.32 (t, 3H), 0.97 (d, 6H).
化合物 2-283: 8.19 (s, 1H)， 7.48 (m， 1H)， 7.07 (m， 2H)， 4.23 (q， 2H)， 2.28 (s, 3H)， 1.53 (t， 3H)， 1.31 (s, 9H)。  Compound 2-283: 8.19 (s, 1H), 7.48 (m, 1H), 7.07 (m, 2H), 4.23 (q, 2H), 2.28 (s, 3H), 1.53 (t, 3H), 1.31 (s , 9H).
化合物 2-285: 8.19 (s, 1H)， 7.46 (m， 1H)， 7.06 (m， 2H)， 4.22 (q， 2H)， 2.27 (s, 3H)， 1.65 (q， 2H) 1.53 (t, 3H)， 1.27 (s, 6H)， 0.77 (t, 3H)。  Compound 2-285: 8.19 (s, 1H), 7.46 (m, 1H), 7.06 (m, 2H), 4.22 (q, 2H), 2.27 (s, 3H), 1.65 (q, 2H) 1.53 (t, 3H), 1.27 (s, 6H), 0.77 (t, 3H).
化合物 2-287： 8.25 (s, 1H)， 7.51 (m， 1H)， 7.08 (m， 2H)， 4.22 (q， 2H)， 3.70 (s, 2H)， 2.28 (s, 3H) Compound 2-287: 8.25 (s, 1H), 7.51 (m, 1H), 7.08 (m, 2H), 4.22 (q, 2H), 3.70 (s, 2H), 2.28 (s, 3H)
1.52 (t, 3H), 1.39 (s, 6H)。 1.52 (t, 3H), 1.39 (s, 6H).
化合物 2-292: 8.24 (s, 1H)， 7.48 (m， 1H)， 7.07 (m， 2H)， 4.31 (q， 2H)， 4.20 (q， 2H)， 2.29 (s, 3H) 1.47 (t, 3H)， 1.35 (t, 3H)。  Compound 2-292: 8.24 (s, 1H), 7.48 (m, 1H), 7.07 (m, 2H), 4.31 (q, 2H), 4.20 (q, 2H), 2.29 (s, 3H) 1.47 (t, 3H), 1.35 (t, 3H).
化合物 2-296: 8.24 (s, 1H)， 7.46 (m， 1H)， 7.06 (m， 2H)， 4.20 (q， 2H)， 4.03 (d, 2H)， 2.29 (s, 3H) 2.03 (m, 1H)， 1.47 (t， 3H)， 0.93 (d, 6H)。  Compound 2-296: 8.24 (s, 1H), 7.46 (m, 1H), 7.06 (m, 2H), 4.20 (q, 2H), 4.03 (d, 2H), 2.29 (s, 3H) 2.03 (m, 1H), 1.47 (t, 3H), 0.93 (d, 6H).
表 3  table 3
Figure imgf000029_0001
化合物 Q Ri R2 R 化合物构型 外观 （熔点 °c)
Figure imgf000029_0001
Compound Q Ri R 2 R Compound Configuration Appearance (Melting Point °c)
3-1 Qi H H CH3 Z或 E 3-1 Qi HH CH 3 Z or E
3-2 Qi H H C(CH3)3 E 黄色油 3-2 Qi HHC(CH 3 ) 3 E Yellow oil
3-3 Qi H H C(CH3)3 Z 白色固体 （ 142-144 °C )3-3 Qi HHC(CH 3 ) 3 Z White solid (142-144 °C)
3-4 Qi H H E 黄色油 ) 3-4 Qi HHE yellow oil )
Figure imgf000030_0001
Figure imgf000030_0001
) )
) ) ) )
Figure imgf000031_0001
Figure imgf000031_0001
Figure imgf000032_0001
-98 Q2 H CI / Z/E=l:l 黄色油
Figure imgf000032_0001
-98 Q 2 H CI / Z/E=l:l yellow oil
CI CI
-99 Q2 H CI H / Z或 E-99 Q 2 H CI H / Z or E
-100 Q2 H CI Z或 E-100 Q 2 H CI Z or E
-101 Q2 H CI ) Z或 E-101 Q 2 H CI ) Z or E
-102 Q2 H CI OCH3 Z或 E-102 Q 2 H CI OCH 3 Z or E
-103 Q2 H CI OCH2CH3 E 白色固体 （ 123-125 °C )-104 Q2 H CI OCH2CH3 Z-103 Q 2 H CI OCH 2 CH 3 E White solid ( 123-125 ° C )-104 Q 2 H CI OCH 2 CH 3 Z
-105 Q2 H CI OCH(CH3)2 E 白色固体 （129-130°C )-106 Q2 H CI OCH(CH3)2 Z-105 Q 2 H CI OCH(CH 3 ) 2 E White solid (129-130 ° C )-106 Q 2 H CI OCH(CH 3 ) 2 Z
-107 Q2 H Br CH3 Z或 E-107 Q 2 H Br CH 3 Z or E
-108 Q2 H Br C(CH3)3 Z或 E-108 Q 2 H Br C(CH 3 ) 3 Z or E
-109 Q2 H Br / Z或 E -109 Q 2 H Br / Z or E
CI CI
-110 Q2 H Br H / Z或 E-110 Q 2 H Br H / Z or E
-111 Q2 H Br Z或 E-111 Q 2 H Br Z or E
-112 Q2 H Br ) Z或 E-112 Q 2 H Br ) Z or E
-113 Q2 H Br 0CH3 Z或 E-113 Q 2 H Br 0CH3 Z or E
-114 Q2 F F CH3 Z或 E-114 Q 2 FF CH 3 Z or E
-115 Q2 F F C(CH3)3 E 黄色油-115 Q 2 FFC(CH 3 ) 3 E Yellow oil
-116 Q2 F F C(CH3)3 Z-116 Q 2 FFC(CH 3 ) 3 Z
-117 Q2 F F / E 白色固体 （139-14CTC ) -118 Q2 F F / Z -117 Q 2 FF / E White solid (139-14CTC) -118 Q 2 FF / Z
CI CI
-119 Q2 F F H / Z或 E-119 Q 2 FFH / Z or E
-120 Q2 F F Z或 E-120 Q 2 FFZ or E
-121 Q2 F F ) Z或 E-121 Q 2 FF ) Z or E
-122 Q2 F F 0CH3 E 白色固体 (85-86°C )-123 Q2 F F OCH(CH3)2 E 黄色油-122 Q 2 FF 0CH3 E White solid (85-86°C)-123 Q 2 FF OCH(CH 3 ) 2 E Yellow oil
-124 Q2 F F OCH(CH3)2 Z-124 Q 2 FF OCH(CH 3 ) 2 Z
-125 Q2 F F OCH2CH(CH3)2 E 黄色油-125 Q 2 FF OCH 2 CH(CH 3 ) 2 E Yellow oil
-126 Q2 F F OCH2CH(CH3)2 Z-126 Q 2 FF OCH 2 CH(CH 3 ) 2 Z
-127 Q2 F CI CH3 Z或 E-127 Q 2 F CI CH 3 Z or E
-128 Q2 F CI C(CH3)3 Z或 E -129 Q2 F CI / Z或 E -128 Q 2 F CI C(CH 3 ) 3 Z or E -129 Q 2 F CI / Z or E
CI CI
-130 Q2 F CI H / Z或 E-130 Q 2 F CI H / Z or E
-131 Q2 F CI Z或 E-131 Q 2 F CI Z or E
-132 Q2 F CI ) Z或 E-132 Q 2 F CI ) Z or E
-133 Q2 F CI OCH3 Z或 E-133 Q 2 F CI OCH 3 Z or E
-134 Q2 CI CI CH3 Z或 E-134 Q 2 CI CI CH 3 Z or E
-135 Q2 CI CI C(CH3)3 Z或 E-135 Q 2 CI CI C(CH 3 ) 3 Z or E
-136 Q2 CI CI / -136 Q 2 CI CI /
卜 Z或 E -137 Q2 CI CI H 尸 Z或 EBu Z or E - 137 Q 2 CI CI H corpse Z or E
-138 Q2 CI CI Z或 E-138 Q 2 CI CI Z or E
-139 Q2 CI CI ) Z或 E-139 Q 2 CI CI ) Z or E
-140 Q2 CI CI 0CH3 Z或 E-140 Q 2 CI CI 0CH3 Z or E
-141 Q3 H H CH3 Z或 E-141 Q 3 HH CH 3 Z or E
-142 Q3 H H CH(CH3)2 E 黄色油-143 Q3 H H CH(CH3)2 Z-142 Q 3 HH CH(CH 3 ) 2 E Yellow oil-143 Q 3 HH CH(CH 3 ) 2 Z
-144 Q3 H H C(CH3)3 E 黄色油-145 Q3 H H C(CH3)3 Z-144 Q 3 HHC(CH 3 ) 3 E yellow oil -145 Q 3 HHC(CH 3 ) 3 Z
-146 Q3 H H / E 黄色油 -147 Q3 H H / Z -148 Q3 H H H 尸 E 黄色油 -149 Q3 H H H 尸 Z-146 Q 3 HH / E Yellow Oil - 147 Q 3 HH / Z -148 Q 3 HHH Corpse E Yellow Oil - 149 Q 3 HHH Corpse Z
-150 Q3 H H E 黄色油-151 Q3 H H M Z-150 Q 3 HHE Yellow Oil - 151 Q 3 HHMZ
-152 Q3 H H K> E 黄色油-153 Q3 H H K> Z-152 Q 3 HH K> E Yellow oil-153 Q 3 HH K> Z
-154 Q3 H H HO Z或 E-154 Q 3 HH HO Z or E
-155 Q3 H H 0CH3 Z/E=l:4 黄色固体 （ 102-104 °C )-156 Q3 H H OCH2CH3 Z/E=l:2 黄色油-157 Q3 H H OCH(CH3)2 Z/E=l:2 黄色油-158 Q3 H H OCH2CH(CH3)2 E 黄色油-159 Q3 H H OCH2CH(CH3)2 Z -160 Q3 H F CH3 Z或 E-155 Q 3 HH 0CH3 Z/E=l:4 yellow solid ( 102-104 ° C )-156 Q 3 HH OCH 2 CH 3 Z/E=l:2 yellow oil-157 Q 3 HH OCH(CH 3 ) 2 Z/E=l:2 yellow oil-158 Q 3 HH OCH 2 CH(CH 3 ) 2 E yellow oil-159 Q 3 HH OCH 2 CH(CH 3 ) 2 Z -160 Q 3 HF CH 3 Z or E
-161 Q3 H F C(CH3)3 Z或 E-161 Q 3 HFC(CH 3 ) 3 Z or E
-162 Q3 H F / -162 Q 3 HF /
卜 Z或 E -163 Q3 H F H 尸 Z或 EBu Z or E -163 Q 3 HFH corpse Z or E
-164 Q3 H F M Z或 E-164 Q 3 HFMZ or E
-165 Q3 H F Z或 E-165 Q 3 HFZ or E
-166 Q3 H F OCH3 Z或 E-166 Q 3 HF OCH 3 Z or E
-167 Q3 H CI CH3 Z或 E-167 Q 3 H CI CH 3 Z or E
-168 Q3 H CI C(CH3)3 E 黄色油-169 Q3 H CI C(CH3)3 Z-168 Q 3 H CI C(CH 3 ) 3 E Yellow oil -169 Q 3 H CI C(CH 3 ) 3 Z
-170 Q3 H CI / -170 Q 3 H CI /
卜 E 黄色油 -171 Q3 H CI / Bu E yellow oil -171 Q 3 H CI /
卜 Z -172 Q3 H CI H 尸 Z或 EZ Z - 172 Q 3 H CI H 尸 Z or E
-173 Q3 H CI M Z或 E-173 Q 3 H CI MZ or E
-174 Q3 H CI Z或 E-174 Q 3 H CI Z or E
-175 Q3 H CI 0CH3 E 黄色油-176 Q3 H CI OCH(CH3)2 Z/E=l:3 黄色油-177 Q3 H CI OCH2CH(CH3)2 Z/E=l:3 黄色油-178 Q3 H Br CH3 Z或 E-175 Q 3 H CI 0CH3 E Yellow oil -176 Q 3 H CI OCH(CH 3 ) 2 Z/E=l:3 Yellow oil-177 Q 3 H CI OCH 2 CH(CH 3 ) 2 Z/E=l :3 yellow oil-178 Q 3 H Br CH 3 Z or E
-179 Q3 H Br C(CH3)3 Z或 E-179 Q 3 H Br C(CH 3 ) 3 Z or E
-180 Q3 H Br / -180 Q 3 H Br /
卜 Z或 E -181 Q3 H Br H 尸 Z或 EBu Z or E -181 Q 3 H Br H corpse Z or E
-182 Q3 H Br M Z或 E-182 Q 3 H Br MZ or E
-183 Q3 H Br ) Z或 E-183 Q 3 H Br ) Z or E
-184 Q3 H Br 0CH3 Z或 E-184 Q 3 H Br 0CH3 Z or E
-185 Q3 F F CH3 Z或 E-185 Q 3 FF CH 3 Z or E
-186 Q3 F F C(CH3)3 Z或 E-186 Q 3 FFC(CH 3 ) 3 Z or E
-187 Q3 F F / Z或 E -188 Q3 F F H 尸 Z或 E-187 Q 3 FF / Z or E -188 Q 3 FFH corpse Z or E
-189 Q3 F F Z或 E-189 Q 3 FFZ or E
-190 Q3 F F Z或 E 3-191 Q3 F F OCH3 Z或 E -190 Q 3 FFZ or E 3-191 Q 3 FF OCH 3 Z or E
3-192 Q3 F CI CH3 Z或 E 3-192 Q 3 F CI CH 3 Z or E
3-193 Q3 F CI C(CH3)3 Z或 E 3-193 Q 3 F CI C(CH 3 ) 3 Z or E
3-194 Q3 F CI / 3-194 Q 3 F CI /
卜 Z或 E  Bu Z or E
CI  CI
3-195 Q3 F CI H / Z或 E 3-195 Q 3 F CI H / Z or E
3-196 Q3 F CI Z或 E 3-196 Q 3 F CI Z or E
3-197 Q3 F CI HO Z或 E 3-197 Q 3 F CI HO Z or E
3-198 Q3 F CI 0CH3 Z或 E 3-198 Q 3 F CI 0CH3 Z or E
3-199 Q3 CI CI CH3 Z或 E 3-199 Q 3 CI CI CH 3 Z or E
3-200 Q3 CI CI C(CH3)3 Z或 E 3-200 Q 3 CI CI C(CH 3 ) 3 Z or E
3-201 Q3 CI CI / 3-201 Q 3 CI CI /
卜 Z或 E  Bu Z or E
3-202 Q3 CI CI H 尸 Z或 E 3-202 Q 3 CI CI H Corpse Z or E
3-203 Q3 CI CI Z或 E 3-203 Q 3 CI CI Z or E
3-204 Q3 CI CI HO Z或 E 3-204 Q 3 CI CI HO Z or E
3-205 Q3 CI CI 0CH3 Z或 E 3-205 Q 3 CI CI 0CH3 Z or E
3-206 Q3 CI CI OCH2CH3 Z或 E 3-206 Q 3 CI CI OCH 2 CH 3 Z or E
部分化合物的 1H NMR (300MHz, CDC13)数据如下： The 1H NMR (300MHz, CDC1 3 ) data for some of the compounds are as follows:
化合物 3-2： 7.98-7.95 (m， 2H)， 7.89 (m， 1H)， 7.79 (m， 1H)， 7.73-7.61 (m， 3H)， 7.49-7.44 (m， 3H), 1.32 (s, 9H)。  Compound 3-2: 7.98-7.95 (m, 2H), 7.89 (m, 1H), 7.79 (m, 1H), 7.73-7.61 (m, 3H), 7.49-7.44 (m, 3H), 1.32 (s, 9H).
化合物 3-3: 7.81-7.79 (m， IH), 7.61-7.56 (m， 3H)， 7.46-7.43 (m， 2H) , 7.37-7.28 (m， 4H)， 1.32 (s, 9H) o  Compound 3-3: 7.81-7.79 (m, IH), 7.61-7.56 (m, 3H), 7.46-7.43 (m, 2H), 7.37-7.28 (m, 4H), 1.32 (s, 9H) o
化合物 3-4： 7.98-7.95 (m， 2H)， 7.89 (m， IH), 7.79 (m， IH), 7.70-7.63 (m， 3H)， 7.47-7.45 (m， IH), 1.58-1.52 (q， 2H)， 1.16 (s, 6H)， 0.58 (t, 3H)。  Compound 3-4: 7.98-7.95 (m, 2H), 7.89 (m, IH), 7.79 (m, IH), 7.70-7.63 (m, 3H), 7.47-7.45 (m, IH), 1.58-1.52 ( q, 2H), 1.16 (s, 6H), 0.58 (t, 3H).
化合物 3-5： 7.77 (m， 1H)， 7.61-7.55 (m， 3H)， 7.45-7.42 (m， 2H)， 7.35-7.28 (m， 3H)， 7.27-7.25 (m, IH), 1.69-1.60 (q, 2H), 1.22 (s, 6H), 0.82-0.77 (t, 3H)。  Compound 3-5: 7.77 (m, 1H), 7.61-7.55 (m, 3H), 7.45-7.42 (m, 2H), 7.35-7.28 (m, 3H), 7.27-7.25 (m, IH), 1.69- 1.60 (q, 2H), 1.22 (s, 6H), 0.82-0.77 (t, 3H).
化合物 3-7: 7.82-7.79 (m， IH), 7.60-7.58 (m， 3H)， 7.45-7.42 (m， 2H)， 7.36-7.29 (m， 3H)， Compound 3-7: 7.82-7.79 (m, IH), 7.60-7.58 (m, 3H), 7.45-7.42 (m, 2H), 7.36-7.29 (m, 3H),
7.28-7.27 (m, IH), 3.62 (s, 2H), 1.36 (s, 6H)。 7.28-7.27 (m, IH), 3.62 (s, 2H), 1.36 (s, 6H).
化合物 3-8: 8.03-7.99 (m, 2H), 7.73-7.72 (m, IH), 7.49-7.45 (m, 5H), 7.05-7.00 (m, 2H), 1.95-1.80 (m, 2H)， 1.02-0.97 (m, 4H)。  Compound 3-8: 8.03-7.99 (m, 2H), 7.73-7.72 (m, IH), 7.49-7.45 (m, 5H), 7.05-7.00 (m, 2H), 1.95-1.80 (m, 2H), 1.02-0.97 (m, 4H).
化合物 3-11： 7.96-7.90 (m， 2H)， 7.80-7.77 (m， 2H)， 7.72-7.60 (m， 3H)， 7.47-7.44 (m， 3H)， 3.05-2.91 (m， IH), 1.80-1.74 (m， 4H)， 1.65-1.54 (m， 4H)。  Compound 3-11: 7.96-7.90 (m, 2H), 7.80-7.77 (m, 2H), 7.72-7.60 (m, 3H), 7.47-7.44 (m, 3H), 3.05-2.91 (m, IH), 1.80-1.74 (m, 4H), 1.65-1.54 (m, 4H).
化合物 3-15： 8.00-7.98 (m， 2H)， 7.89 (m， 1H)， 7.80 (m， 1H)， 7.72 (s, 1H)， 7.73-7.67 (m， 2H)， Compound 3-15: 8.00-7.98 (m, 2H), 7.89 (m, 1H), 7.80 (m, 1H), 7.72 (s, 1H), 7.73-7.67 (m, 2H),
7.46 (m， 3H)， 7.49-7.44 ( q， 2H)， 4.28-4.20 ( q， 2H)， 1.33-1.25 (t， 3H)。 7.46 (m, 3H), 7.49-7.44 (q, 2H), 4.28-4.20 (q, 2H), 1.33-1.25 (t, 3H).
化合物 3-26： 8.26 (m， IH), 7.89 (m， IH), 7.83 (s, IH), 7.78 (m， IH), 7.71 (m， 2H)， 7.49 (m， lH), 7.38 ( m, 2H), 1.17 (s, 9H)。 Compounds 3-26: 8.26 (m, IH), 7.89 (m, IH), 7.83 (s, IH), 7.78 (m, IH), 7.71 (m, 2H), 7.49 (m, lH), 7.38 (m, 2H), 1.17 (s, 9H).
化合物 3-28： 8.26 (m， IH), 7.90 (m， 1H)， 7.83 (s, IH), 7.80 (m， 1H)， 7.67 (m, 2H)， 7.50 (m， IH), 7.39 ( m, 2H), 1.53 (q, 2H)， 1.15 (s, 6H), 0.57 (t, 3H)。  Compounds 3-28: 8.26 (m, IH), 7.90 (m, 1H), 7.83 (s, IH), 7.80 (m, 1H), 7.67 (m, 2H), 7.50 (m, IH), 7.39 ( m , 2H), 1.53 (q, 2H), 1.15 (s, 6H), 0.57 (t, 3H).
化合物 3-45: 7.78 (m, IH), 7.53 (m, 3H), 7.32 (s, IH), 7.30 (m, IH), 6.93 (m, 2H), 1.31 (s, 9H) o  Compound 3-45: 7.78 (m, IH), 7.53 (m, 3H), 7.32 (s, IH), 7.30 (m, IH), 6.93 (m, 2H), 1.31 (s, 9H) o
化合物 3-47： 7.73 (m, 1H)， 7.53 (m, 3H), 7.33 (s, 1H)， 7.30 (m, IH), 6.93 (m, 2H), 1.60 (q, 2H), 1.19 (s, 6H), 0.89 (t, 3H) o  Compound 3-47: 7.73 (m, 1H), 7.53 (m, 3H), 7.33 (s, 1H), 7.30 (m, IH), 6.93 (m, 2H), 1.60 (q, 2H), 1.19 (s , 6H), 0.89 (t, 3H) o
化合物 3-52： 7.97 (s, 1H)， 7.93 (m, 1H)， 7.81 (m， 1H)， 7.74 (m, 2H), 7.41 (m， 1H)， 7.06 (m, 2H)， 4.23 (q, 2H)， 1.26 (t, 3H)。  Compounds 3-52: 7.97 (s, 1H), 7.93 (m, 1H), 7.81 (m, 1H), 7.74 (m, 2H), 7.41 (m, 1H), 7.06 (m, 2H), 4.23 (q , 2H), 1.26 (t, 3H).
化合物 3-54: 7.98 (s, IH), 7.93 (m， 1H)， 7.81 (m， 2H)， 7.68 (m， 2H)， 7.41 (m， 1H)， 7.05 (m， Compound 3-54: 7.98 (s, IH), 7.93 (m, 1H), 7.81 (m, 2H), 7.68 (m, 2H), 7.41 (m, 1H), 7.05 (m,
2H), 4.85 (hept., IH), 1.23 (d, 6H)。 2H), 4.85 (hept., IH), 1.23 (d, 6H).
化合物 3-57： 7.91 (s, 1H)， 7.88 (m， 1H)， 7.78 (m， 1H)， 7.67 (m， 2H)， 7.34 (m， 2H)， 7.11 (m， IH), 1.09 (s, 9H)。  Compounds 3-57: 7.91 (s, 1H), 7.88 (m, 1H), 7.78 (m, 1H), 7.67 (m, 2H), 7.34 (m, 2H), 7.11 (m, IH), 1.09 (s , 9H).
化合物 3-59： 7.90 (s, 1H)， 7.87 (m, 1H)， 7.76 (m， 1H)， 7.64 (m, 2H)， 7.42 (m， 1H)， 7.34 (m, 1H)， 7.13 (m, 1H)， 1.61 (q, 2H)， 1.21 (s, 6H), 0.91 (t, 3H)。  Compounds 3-59: 7.90 (s, 1H), 7.87 (m, 1H), 7.76 (m, 1H), 7.64 (m, 2H), 7.42 (m, 1H), 7.34 (m, 1H), 7.13 (m , 1H), 1.61 (q, 2H), 1.21 (s, 6H), 0.91 (t, 3H).
化合物 3-65： 8.03 (s, IH), 7.91 (m， 1H)， 7.80 (m， IH), 7.68 (m， 2H)， 7.38 (m， 2H)， 7.13 (m， 1H)， 4.17 (q, 2H), 1.18 (t, 3H)。  Compound 3-65: 8.03 (s, IH), 7.91 (m, 1H), 7.80 (m, IH), 7.68 (m, 2H), 7.38 (m, 2H), 7.13 (m, 1H), 4.17 (q , 2H), 1.18 (t, 3H).
化合物 3-76： 8.00 (s, 1H)， 7.97-7.92 (m， 2H)， 7.81-7.75 (m， 2H)， 7.69 (m， 2H)， 7.46 (m， 3H)， 1.27 (s, 9H)。  Compound 3-76: 8.00 (s, 1H), 7.97-7.92 (m, 2H), 7.81-7.75 (m, 2H), 7.69 (m, 2H), 7.46 (m, 3H), 1.27 (s, 9H) .
化合物 3-77： 7.98-7.90 (m， 2H), 7.82-7.77 (m， 2H)， 7.72 (s, IH), 7.69 (m， 2H)， 7.46 (m, 3H)， Compound 3-77: 7.98-7.90 (m, 2H), 7.82-7.77 (m, 2H), 7.72 (s, IH), 7.69 (m, 2H), 7.46 (m, 3H),
1.35 (s, 9H) c 1.35 (s, 9H) c
化合物 3-79： 8.09-8.05 (m， 2H), 8.03 (s, 1H)， 7.84-7.76 (m, 2H), 7.70-7.62 (m, 2H)， 7.50-7.44 (m, 3H), 1.59 (q, 2H), 1.27 (s, 6H), 0.67 (t, 3H)。  Compound 3-79: 8.09-8.05 (m, 2H), 8.03 (s, 1H), 7.84-7.76 (m, 2H), 7.70-7.62 (m, 2H), 7.50-7.44 (m, 3H), 1.59 ( q, 2H), 1.27 (s, 6H), 0.67 (t, 3H).
化合物 3-84： 8.01 (s, 1H)， 7.94-7.90 (m， 2H)， 7.82-7.77 (m， 2H)， 7.69 (m， 2H)， 7.46 (m， 3H)， 4.24 (q，2H)， 1.28 (t，3H)。  Compound 3-84: 8.01 (s, 1H), 7.94-7.90 (m, 2H), 7.82-7.77 (m, 2H), 7.69 (m, 2H), 7.46 (m, 3H), 4.24 (q, 2H) , 1.28 (t, 3H).
化合物 3-86： 8.13 (s, IH), 8.11-8.08 (m, 2H), 7.88-7.80 (m, 2H), 7.74-7.63 (m, 2H)， 7.49-7.44 (m， 3H), 4.87 (hept., IH), 1.30 (d, 6H)。  Compound 3-86: 8.13 (s, IH), 8.11-8.08 (m, 2H), 7.88-7.80 (m, 2H), 7.74-7.63 (m, 2H), 7.49-7.44 (m, 3H), 4.87 ( Hept., IH), 1.30 (d, 6H).
化合物 3-96： 8.12 (s, 1H)， 7.99 (m, IH), 7.85 (m， 1H)， 7.78 (m, IH), 7.67 (m， 2H), 7.53 (m, IH), 7.40 (m, 2H), 1.27 (s, 9H)。  Compound 3-96: 8.12 (s, 1H), 7.99 (m, IH), 7.85 (m, 1H), 7.78 (m, IH), 7.67 (m, 2H), 7.53 (m, IH), 7.40 (m , 2H), 1.27 (s, 9H).
化合物 3-103： 8.22 (s, IH), 8.07 (m， 1H)， 7.88 (m， IH), 7.81 (m， 1H)， 7.71 (m， 2H)， 7.52 (m， Compound 3-103: 8.22 (s, IH), 8.07 (m, 1H), 7.88 (m, IH), 7.81 (m, 1H), 7.71 (m, 2H), 7.52 (m,
IH), 7.40 (m， 2H)， 4.25 (q， 2H)， 1.31 (t， 3H)。 IH), 7.40 (m, 2H), 4.25 (q, 2H), 1.31 (t, 3H).
化合物 3-105： 8.22 (s, IH), 8.07 (m, IH), 7.88 (m, IH), 7.81 (m, IH), 7.70 (m, 2H)， 7.52 (m, IH), 7.40 (m， 2H)， 4.85 (hept., IH), 1.28 (d， 6H)。  Compound 3-105: 8.22 (s, IH), 8.07 (m, IH), 7.88 (m, IH), 7.81 (m, IH), 7.70 (m, 2H), 7.52 (m, IH), 7.40 (m , 2H), 4.85 (hept., IH), 1.28 (d, 6H).
化合物 3-115： 8.15 (s, 1H)， 7.80 (m， 2H)， 7.66 (m， 2H), 7.46 (m， 1H)， 7.06 (m， 2H), 1.27 (s, 9H) o  Compound 3-115: 8.15 (s, 1H), 7.80 (m, 2H), 7.66 (m, 2H), 7.46 (m, 1H), 7.06 (m, 2H), 1.27 (s, 9H) o
化合物 3-117： 8.14 (s, IH), 7.81 (m, 2H), 7.65 (m， 2H)， 7.47 (m, 1H)， 7.06 (m， 2H), 1.59 (q, 2H)， 1.22 (s, 6H), 0.92 (t, 3H)。 Compound 3-117: 8.14 (s, IH), 7.81 (m, 2H), 7.65 (m, 2H), 7.47 (m, 1H), 7.06 (m, 2H), 1.59 (q, 2H), 1.22 (s, 6H), 0.92 (t, 3H).
化合物 3-122： 8.25 (s, 1H)， 7.84 (m， 2H)， 7.73 (m， 2H)， 7.47 (m， 1H)， 7.06 (m， 2H)， 3.85 (s, Compound 3-122: 8.25 (s, 1H), 7.84 (m, 2H), 7.73 (m, 2H), 7.47 (m, 1H), 7.06 (m, 2H), 3.85 (s,
3H)。 3H).
化合物 3-123： 8.26 (s, 1H), 7.85 (m, 2H), 7.72 (m, 2H), 7.47 (m, 1H), 7.06 (m, 2H), 4.86 (hept., 1H), 1.28 (d, 6H)。  Compound 3-123: 8.26 (s, 1H), 7.85 (m, 2H), 7.72 (m, 2H), 7.47 (m, 1H), 7.06 (m, 2H), 4.86 (hept., 1H), 1.28 ( d, 6H).
化合物 3-125： 8.25 (s, 1H)， 7.85 (m， 2H)， 7.72 (m， 2H)， 7.47 (m， 1H)， 7.06 (m， 2H)， 3.97 (d， 2H)， 1.97 (m, 1H)， 0.95 (d, 6H)。  Compound 3-125: 8.25 (s, 1H), 7.85 (m, 2H), 7.72 (m, 2H), 7.47 (m, 1H), 7.06 (m, 2H), 3.97 (d, 2H), 1.97 (m , 1H), 0.95 (d, 6H).
化合物 3-142： 7.96 (d, 1H)， 7.91 (d, 1H)， 7.79-7.67 (m， 3H)， 7.49-7.44 (m， 3H)， 7.36-7.33 (m. 2H)， 6.80 (d, 1H)， 2.83-2.79 (m， 1H)， 1.20 (d, 6H)。  Compound 3-142: 7.96 (d, 1H), 7.91 (d, 1H), 7.79-7.67 (m, 3H), 7.49-7.44 (m, 3H), 7.36-7.33 (m. 2H), 6.80 (d, 1H), 2.83-2.79 (m, 1H), 1.20 (d, 6H).
化合物 3-144： 7.96 (d, 1H), 7.90 (d, 1H), 7.77-7.63 (m, 3H), 7.50-7.45 (m, 3H), 7.36-7.33 (m. Compound 3-144: 7.96 (d, 1H), 7.90 (d, 1H), 7.77-7.63 (m, 3H), 7.50-7.45 (m, 3H), 7.36-7.33 (m.
2H), 6.80 (d, 1H)， 1.23 (s，9H)。 2H), 6.80 (d, 1H), 1.23 (s, 9H).
化合物 3-146： 7.94 (d, 1H), 7.91 (d, 1H), 7.77-7.63 (m, 3H), 7.47 (m, 3H), 7.36-7.33 (m, 2H), 6.80 (d, 1H), 1.62-1.59 (q, 2H), 1.19 (s, 6H) , 0.57 (t, 3H)。  Compound 3-146: 7.94 (d, 1H), 7.91 (d, 1H), 7.77-7.63 (m, 3H), 7.47 (m, 3H), 7.36-7.33 (m, 2H), 6.80 (d, 1H) , 1.62-1.59 (q, 2H), 1.19 (s, 6H), 0.57 (t, 3H).
化合物 3-148： 7.96 (d, 1H), 7.91 (m, 1H), 7.79-7.67 (m, 3H), 7.49-7.44 (m, 3H), 7.36-7.33 (m， 2H)， 6.80 (d, 1H), 3.63 (s, 2H)， 1.30 (s, 6H)。  Compound 3-148: 7.96 (d, 1H), 7.91 (m, 1H), 7.79-7.67 (m, 3H), 7.49-7.44 (m, 3H), 7.36-7.33 (m, 2H), 6.80 (d, 1H), 3.63 (s, 2H), 1.30 (s, 6H).
化合物 3-150： 7.96 (d, 1H), 7.91 (d, 1H), 7.79-7.67 (m, 3H), 7.49-7.44 (m, 3H), 7.36-7.33 (m. 2H)， 6.80 (d, 1H)， 1.90-1.80 (m， 1H)， 1.09-1.03 (m， 4H)。  Compound 3-150: 7.96 (d, 1H), 7.91 (d, 1H), 7.79-7.67 (m, 3H), 7.49-7.44 (m, 3H), 7.36-7.33 (m. 2H), 6.80 (d, 1H), 1.90-1.80 (m, 1H), 1.09-1.03 (m, 4H).
化合物 3-152： 7.96 (d, 1H), 7.91 (d, 1H), 7.79-7.67 (m, 3H), 7.49-7.44 (m, 3H), 7.36-7.33 (m. 2H)， 6.77 (d， 1H), 3.42-3.36 (m， 1H), 2.36-2.21 (m， 4H)， 2.04-1.94 (m，2H)。  Compound 3-152: 7.96 (d, 1H), 7.91 (d, 1H), 7.79-7.67 (m, 3H), 7.49-7.44 (m, 3H), 7.36-7.33 (m. 2H), 6.77 (d, 1H), 3.42-3.36 (m, 1H), 2.36-2.21 (m, 4H), 2.04-1.94 (m, 2H).
化合物 3-158： 8.00 (d, 1H), 7.91 (d, 1H), 7.79-7.67 (m, 3H), 7.49-7.44 (m, 3H), 7.36-7.33 (m. Compound 3-158: 8.00 (d, 1H), 7.91 (d, 1H), 7.79-7.67 (m, 3H), 7.49-7.44 (m, 3H), 7.36-7.33 (m.
2H)， 6.87 (d， 1H), 3.95 (d, 2H) , 2.06-1.91 (m， 1H) , 0.91 (d, 6H)。 2H), 6.87 (d, 1H), 3.95 (d, 2H), 2.06-1.91 (m, 1H), 0.91 (d, 6H).
化合物 3-168： 7.94 (d， 1H)， 7.88 (d, 1H)， 7.78 (d, 1H)， 7.71-7.63 (m， 4H)， 7.55-7.52 (m， 1H)， Compound 3-168: 7.94 (d, 1H), 7.88 (d, 1H), 7.78 (d, 1H), 7.71-7.63 (m, 4H), 7.55-7.52 (m, 1H),
7.39- 7.37 (m， 1H), 6.80 (d, 1H), 1.23 (s, 9H)。 7.39- 7.37 (m, 1H), 6.80 (d, 1H), 1.23 (s, 9H).
化合物 3-170： 7.94 (d, 1H), 7.87 (d, 1H), 7.69-7.62 (m， 4H)， 7.52 (d, 1H), 7.40-7.37 (m， 2H)， 6.81 (d, 1H), 1.62-1.59 (m, 2H), 1.19 (s, 6H) , 0.57 (t, 3H)。  Compound 3-170: 7.94 (d, 1H), 7.87 (d, 1H), 7.69-7.62 (m, 4H), 7.52 (d, 1H), 7.40-7.37 (m, 2H), 6.81 (d, 1H) , 1.62-1.59 (m, 2H), 1.19 (s, 6H), 0.57 (t, 3H).
化合物 3-175: 8.00 (d, 1H)， 7.90 (d, 1H)， 7.79 (d, 1H)， 7.72-7.65 (m， 4H)， 7.52 (d， 1H)， Compound 3-175: 8.00 (d, 1H), 7.90 (d, 1H), 7.79 (d, 1H), 7.72-7.65 (m, 4H), 7.52 (d, 1H),
7.40- 7.34 (m， 2H)， 6.88 (d, 1H), 3.81 (s, 3H)。 7.40- 7.34 (m, 2H), 6.88 (d, 1H), 3.81 (s, 3H).
本发明的丙烯腈类化合物具有高的杀虫活性， 可防治小菜蛾、 甜菜夜蛾、 斜纹夜蛾、 棉 铃虫、 草地粘虫、 粉纹夜蛾、 豌蚜、 豆蚜、 甜菜蚜、 棉蚜、 苹果蚜、 桃蚜、 玉米蚜、 粉虱、 叶蝉、 飞虱、 稻飞虱、 粉蚧、 棉网蝽、 番茄盲蝽、 稻绿蝽、 稻臭蝽、 棉蓟马、 苜蓿蓟马、 黄 豆蓟马、 马铃薯甲虫、 叩甲、 蝇、 蚊等多种害虫。 同已知的丙烯腈类化合物相比， 本发明的 丙烯腈类化合物具有意想不到的高杀虫活性。 因此， 本发明还包括通式 I化合物用于控制害 虫的用途。  The acrylonitrile compound of the invention has high insecticidal activity and can control Plutella xylostella, Spodoptera exigua, Spodoptera litura, Helicoverpa armigera, Grass armyworm, Spodoptera litura, Bean, Soybean, Beet, and cotton aphid , apple tart, peach aphid, corn bran, whitefly, leafhopper, planthopper, rice planthopper, whitefly, cotton net, tomato blind dragonfly, rice green grass, rice skunk, cotton scorpion horse, hummer, Soybeans, potato beetles, armor, flies, mosquitoes and other pests. The acrylonitrile compound of the present invention has unexpectedly high insecticidal activity as compared with the known acrylonitrile compound. Accordingly, the present invention also encompasses the use of a compound of formula I for controlling pests.
本发明还包括以通式 I化合物作为活性组分的杀虫组合物。 该杀虫组合物中活性组分的 重量百分含量在 1-99%之间。 该杀虫组合物中还包括农业、 林业或卫生上可接受的载体。 本发明的组合物可以制剂的形式施用。 通式 I化合物作为活性组分溶解或分散于载体中 或配制成制剂以便作为杀虫剂使用时更易于分散。 例如： 这些化学制剂可被制成可湿性粉剂 或乳油。 在这些组合物中， 至少加入一种液体或固体载体， 并且当需要时可以加入适当的表 面活性剂。 The present invention also encompasses pesticidal compositions having a compound of formula I as an active ingredient. The active ingredient in the pesticidal composition is present in an amount between 1 and 99% by weight. Also included in the pesticidal composition are agricultural, forestry or hygienic acceptable carriers. The compositions of the invention may be administered in the form of a formulation. The compound of the formula I is dissolved or dispersed in the carrier as an active ingredient or formulated into a formulation for easier dispersion when used as an insecticide. For example: These chemicals can be formulated as wettable powders or creams. In these compositions, at least one liquid or solid carrier is added, and a suitable surfactant may be added as needed.
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需要控制的害虫 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 50克到 500克。  The technical solution of the present invention also includes a method of controlling pests: The insecticidal composition of the present invention is applied to a pest to be controlled or a growth medium thereof. A more suitable effective amount is usually selected from 10 g to 1000 g per hectare, and an effective amount is preferably 50 g to 500 g per hectare.
对于某些应用，例如在农业上可在本发明的杀虫组合物中加入一种或多种其它的杀菌剂、 杀虫剂、 除草剂、 植物生长调节剂或肥料等， 由此可产生附加的优点和效果。  For certain applications, for example, in agriculture, one or more other fungicides, insecticides, herbicides, plant growth regulators or fertilizers may be added to the pesticidal composition of the invention, thereby producing additional The advantages and effects.
应明确的是， 在本发明的权利要求所限定的范围内， 可进行各种变换和改动。  It is to be understood that various changes and modifications may be made within the scope of the appended claims.
具体实》式 Concrete
下列合成实施例及生测试验结果可用来进一步说明本发明， 但不意味着限制本发明。 合成实施例  The following synthetic examples and bioassay results can be used to further illustrate the invention, but are not meant to limit the invention. Synthesis example
实施例 1、 化合物 1-2、 1-3的制备  Example 1. Preparation of Compounds 1-2, 1-3
(1) 4-氯甲基 -2-苯基噻唑的制备
Figure imgf000039_0001
(1) Preparation of 4-chloromethyl-2-phenylthiazole
Figure imgf000039_0001
向三口瓶内加入硫代苯甲酰胺 (20.00克， 0.146摩尔），甲醇 200毫升， 1, 3-二氯丙酮（22.21 克， 0.157摩尔）， 升温至回流， 回流反应 3小时。 反应结束后降温至 30°C以下， 反应液倾入 50毫升水中， 用 3x50毫升乙酸乙酯萃取， 所得有机相用饱和碳酸氢钠水溶液（50毫升）、 饱 和氯化钠水溶液 （50毫升） 洗涤后， 用无水硫酸镁干燥， 减压浓縮后， 残余物通过柱色谱分 离（淋洗液： 乙酸乙酯:石油醚 = 1:10)得 21.00克 4-氯甲基 -2-苯基噻唑，黄色油， 收率： 69%。  To a three-necked flask was added thiobenzamide (20.00 g, 0.146 mol), methanol (200 ml, 1, 3-dichloroacetone (22.21 g, 0.157 mol), and the mixture was warmed to reflux and refluxed for 3 hours. After the completion of the reaction, the temperature was lowered to 30 ° C or less, and the reaction mixture was poured into 50 ml of water and extracted with 3×50 ml of ethyl acetate. The obtained organic phase was washed with saturated aqueous sodium hydrogen carbonate (50 ml) and saturated aqueous sodium chloride (50 ml) After drying over anhydrous magnesium sulfate and concentrating under reduced pressure, the residue was purified by column chromatography (eluent: ethyl acetate: petroleum ether = 1:10). Thiazole, yellow oil, yield: 69%.
(2) 2-(2-苯基 -4-基)乙腈的制备
Figure imgf000039_0002
(2) Preparation of 2-(2-phenyl-4-yl)acetonitrile
Figure imgf000039_0002
向反应瓶内加入氰化钠 （4.91克， 0.100摩尔）， 水 100毫升， 滴加 4-氯甲基 -2-苯基噻唑 (21.00克， 0.100摩尔） 的乙醇 （100毫升） 溶液， 滴加完毕， 升温至回流， 回流 16小时。 反应结束后将反应液倾入 200毫升水中， 用 3x200毫升乙酸乙酯萃取， 所得有机相用饱和氯 化钠水溶液 （200 毫升） 洗涤后， 用无水硫酸镁干燥， 减压浓縮后， 残余物通过柱色谱分离 (淋洗液： 乙酸乙酯:石油醚 = 1:10) 得 13.22克 2-(2-苯基噻唑 -4-基)乙腈， 黄色固体， 收率 66 %。  Add sodium cyanide (4.91 g, 0.100 mol), 100 ml of water to the reaction flask, and add a solution of 4-chloromethyl-2-phenylthiazole (21.00 g, 0.100 mol) in ethanol (100 ml) dropwise. After completion, the temperature was raised to reflux and refluxed for 16 hours. After the completion of the reaction, the reaction mixture was poured into EtOAc EtOAc (EtOAc m. The product was separated by column chromatography (EtOAc:EtOAc:EtOAc:EtOAc)
(3) 3-(2-氯 -4-甲基噻唑 -5-基) -3-羟基 -2-(2-苯基噻唑 -4-基)丙烯腈的制备
Figure imgf000040_0001
(3) Preparation of 3-(2-chloro-4-methylthiazol-5-yl)-3-hydroxy-2-(2-phenylthiazol-4-yl)acrylonitrile
Figure imgf000040_0001
在冰水浴下， 向反应瓶内加入 2-(2-苯基噻唑 -4-基)乙腈 （3.00克， 0.015摩尔）， （2-氯 -4- 甲基噻唑 -5-基) (1H-吡唑小基)甲酮（3.72克， 0.018摩尔）， 四氢呋喃 40毫升， 搅拌约 1小时， 分批加入叔丁醇钾 （3.36克， 0.030摩尔）， 加料结束， 反应液升温至室温， 室温反应 6小时。 反应液倾入 150毫升水中，用 100毫升乙酸乙酯萃取，所得水相用浓盐酸调酸至 pH值为 2~3， 用 3x150毫升乙酸乙酯萃取， 有机相经饱和碳酸氢钠水溶液 （150毫升）、 饱和氯化钠水溶液 ( 150毫升） 洗涤后， 用无水硫酸镁干燥， 浓縮后得 2.63克 3-(2-氯 -4-甲基噻唑 -5-基) -3-羟基 -2-(2-苯基噻唑 -4-基)丙烯腈， 黄色固体， 收率 51 %。  In an ice water bath, 2-(2-phenylthiazol-4-yl)acetonitrile (3.00 g, 0.015 mol), (2-chloro-4-methylthiazole-5-yl) (1H-) was added to the reaction flask. Pyrazole small base) ketone (3.72 g, 0.018 mol), tetrahydrofuran 40 ml, stirred for about 1 hour, potassium tert-butoxide (3.36 g, 0.030 mol) was added portionwise, the reaction was completed, the reaction was warmed to room temperature, and reacted at room temperature. 6 hours. The reaction mixture was poured into 150 ml of water and extracted with 100 ml of ethyl acetate. The obtained aqueous phase was acidified with concentrated hydrochloric acid to pH 2-3, and extracted with 3×150 ml of ethyl acetate. After washing with a saturated aqueous solution of sodium chloride (150 ml), dried over anhydrous magnesium sulfate and evaporated. 2-(2-Phenylthiazol-4-yl)acrylonitrile, yellow solid, yield 51%.
(4) 化合 1-2的制备  (4) Preparation of compound 1-2
Figure imgf000040_0002
Figure imgf000040_0002
在冰水浴下， 向反应瓶内加入 3-(2-氯 -4-甲基噻唑 -5-基) -3-羟基 -2-(2-苯基噻唑 -4-基)丙烯 腈（0.36克， 0.001摩尔）， 乙腈 10毫升， 三乙胺（0.10克， 0.001摩尔）， 再将新戊酰氯 (0.12 克， 0.001摩尔） 滴加到反应瓶内， 滴加结束， 升温至室温搅拌反应 2小时， 反应液倾入 50 毫升水中， 用乙酸乙酯 100毫升萃取， 所得有机相用饱和碳酸氢钠水溶液 （100毫升）、 饱和 氯化钠水溶液洗涤后 （100毫升）， 用无水硫酸镁干燥， 减压浓縮后， 残余物通过柱色谱分离 (淋洗液： 乙酸乙酯:石油醚 = 1:20)， 得到 0.21克化合物 1-2， 黄色油， 收率 49%。  In the ice water bath, 3-(2-chloro-4-methylthiazol-5-yl)-3-hydroxy-2-(2-phenylthiazol-4-yl)acrylonitrile (0.36 g) was added to the reaction flask. , 0.001 mol), acetonitrile 10 ml, triethylamine (0.10 g, 0.001 mol), and then pivaloyl chloride (0.12 g, 0.001 mol) was added dropwise to the reaction flask, the dropwise addition was completed, and the mixture was warmed to room temperature and stirred for 2 hours. The reaction mixture was poured into 50 ml of EtOAc (EtOAc m. After concentration under reduced pressure, the residue was evaporated to mjjjjjjjjjjjjj
(5) 化合物 1-3的制备  (5) Preparation of Compound 1-3
Figure imgf000040_0003
Figure imgf000040_0003
向反应瓶内加入 3-(2-氯 -4-甲基噻唑 -5-基) -3-羟基 -2-(2-苯基噻唑 -4-基)丙烯腈 （0.72克， 0.002摩尔）， 碳酸氢钠 （0.34克， 0.004摩尔）， 甲苯 20毫升， 4-二甲氨基吡啶 (催化量)， 四 丁基溴化铵 (催化量)， 升温至 100°C， 再将新戊酰氯 （0.24克， 0.002摩尔） 滴加到反应瓶内， 滴加结束， 继续反应 2小时。 反应液降温至 30°C以下， 反应液倾入 50毫升水中， 用乙酸乙 酯 100毫升萃取， 所得有机相用饱和碳酸氢钠水溶液 （100毫升）、 饱和氯化钠水溶液洗涤后 ( 100毫升）， 用无水硫酸镁干燥， 减压浓縮后， 残余物通过柱色谱分离（淋洗液： 乙酸乙酯: 石油醚 = 1:30)， 得到 0.30克化合物 1-3， 黄色油， 收率 41%。 实施例 2、 化合物 2-7的制备 To the reaction flask was added 3-(2-chloro-4-methylthiazol-5-yl)-3-hydroxy-2-(2-phenylthiazol-4-yl)acrylonitrile (0.72 g, 0.002 mol). Sodium bicarbonate (0.34 g, 0.004 mol), toluene 20 ml, 4-dimethylaminopyridine (catalytic amount), tetrabutylammonium bromide (catalytic amount), warmed to 100 ° C, then pivaloyl chloride (0.24 G, 0.002 mol) was added dropwise to the reaction flask, and the addition was completed, and the reaction was continued for 2 hours. The reaction solution was cooled to 30 ° C or less, and the reaction mixture was poured into 50 ml of water and extracted with ethyl acetate (100 ml). The obtained organic layer was washed with saturated aqueous sodium hydrogen carbonate (100 ml) and saturated aqueous sodium chloride (100 ml) After drying over anhydrous magnesium sulfate, and the residue was evaporated to dryness crystalljjjjjjjjjjjjjjjj 41%. Example 2 Preparation of Compound 2-7
(1) 3-羟基 -3-(1-乙基 -3-甲基吡唑 -5-基) -2-(2-苯基噻唑 -4-基)丙烯腈的合成  (1) Synthesis of 3-hydroxy-3-(1-ethyl-3-methylpyrazole-5-yl)-2-(2-phenylthiazole-4-yl)acrylonitrile
Figure imgf000041_0001
Figure imgf000041_0001
在冰水浴下， 向 100毫升反应瓶内加入 2-苯基 -4-氰甲基噻唑 （3.00克， 0.015摩尔） ， 无水四氢呋喃 25毫升， （1-乙基 -3-甲基 -1H-吡唑 -5-基) (1H-吡唑小基)甲酮 （1.02克， 0.005摩 尔） ， 再将叔丁醇钾 （3.37克， 0.030摩尔） 少量多次地加入到反应瓶内， 升温至室温搅拌反 应 4小时， 将反应液倾入 50毫升水中， 用乙酸乙酯 2x20毫升洗涤， 弃去有机相。 将水相用 盐酸调节体系 pH=2〜3， 再用乙酸乙酯 3x25毫升充分萃取， 用无水硫酸镁干燥， 减压浓縮得 到 2.86克中间体 3-羟基 -3-(1-乙基 -3-甲基吡唑 -5-基) -2-(2-苯基噻唑 -4-基)丙烯腈， 褐色油， 收 率 57%。  To a 100 ml reaction flask was added 2-phenyl-4-cyanomethylthiazole (3.00 g, 0.015 mol) in anhydrous water bath, 25 ml of anhydrous tetrahydrofuran, (1-ethyl-3-methyl-1H- Pyrazol-5-yl) (1H-pyrazole small) ketone (1.02 g, 0.005 mol), then potassium t-butoxide (3.37 g, 0.030 mol) was added in small portions to the reaction flask, and the temperature was raised to The reaction was stirred at room temperature for 4 hours, and the mixture was poured into 50 ml of water, washed with ethyl acetate 2x 20 ml, and the organic phase was discarded. The aqueous phase was adjusted to pH 2 to 3 with hydrochloric acid, and then extracted with ethyl acetate (3×25 ml). 3-methylpyrazol-5-yl)-2-(2-phenylthiazol-4-yl)acrylonitrile, brown oil, yield 57%.
(2) 化合物 2-7的合成  (2) Synthesis of compound 2-7
Figure imgf000041_0002
Figure imgf000041_0002
在冰水浴下， 向 50毫升反应瓶内依次加入 3-羟基 -3-(1-乙基 -3-甲基吡唑 -5-基) -2-(2-苯基 噻唑 -4-基)丙烯腈 （0.30克， 0.001摩尔) ， 乙腈 15毫升和三乙胺 （0.47克， 0.005摩尔) ， 再将特戊酰氯（0.47克， 0.004摩尔）滴加到反应瓶内， 升温至室温搅拌反应 4小时， 反应液 倾入 50毫升水中， 用乙酸乙酯萃取 （2x50毫升） ， 所得有机相用 15毫升饱和碳酸氢钠水溶 液、 25毫升饱和氯化钠水溶液洗涤后， 用无水硫酸镁干燥， 减压浓縮后， 残余物通过柱色谱 分离 （淋洗液： 乙酸乙酯:石油醚 = 1:8) 得到 0.15克化合物 2-7， 黄色油， 收率 39%。  In a 50 ml reaction flask, 3-hydroxy-3-(1-ethyl-3-methylpyrazol-5-yl)-2-(2-phenylthiazol-4-yl) was added in an ice water bath. Acrylonitrile (0.30 g, 0.001 mol), acetonitrile 15 ml and triethylamine (0.47 g, 0.005 mol), then pivaloyl chloride (0.47 g, 0.004 mol) was added dropwise to the reaction flask, and the mixture was warmed to room temperature and stirred for reaction 4 The reaction mixture was poured into 50 ml of water and extracted with ethyl acetate (2×50 ml). The obtained organic phase was washed with 15 ml of saturated aqueous sodium hydrogen carbonate and 25 ml of saturated aqueous sodium chloride and dried over anhydrous magnesium sulfate. After concentration by pressure, the residue was purified by column chromatography (EtOAc:EtOAc:EtOAc:EtOAc:
实施例 3、 化合物 3-4、 3-5的制备  Example 3, Preparation of Compounds 3-4, 3-5
(1) 3-(2- (三氟甲基)苯基) -3-羟基 -2-(2-苯基噻唑 -5-基)丙烯腈的合成  (1) Synthesis of 3-(2-(trifluoromethyl)phenyl)-3-hydroxy-2-(2-phenylthiazole-5-yl)acrylonitrile
Figure imgf000041_0003
Figure imgf000041_0003
在冰水浴下， 向反应瓶内加入 4-氰甲基 -2-苯基噻唑 （2.00克， 0.010摩尔）， （2- (三氟甲 基)苯基) (1H-吡唑 -1-基)甲酮（2.40克， 0.010摩尔）， 四氢呋喃 20毫升， 搅拌约 1小时， 分批 加入叔丁醇钾 （2.24克， 0.020摩尔）， 加料结束， 反应液升温至室温， 室温反应 6小时。 反 应液倾入 100毫升水中， 用 100毫升乙酸乙酯萃取， 所得水相用浓盐酸调酸至 pH值为 2~3， 用 3x100毫升乙酸乙酯萃取， 有机相经饱和碳酸氢钠水溶液 （100毫升）、 饱和氯化钠水溶液 ( 100毫升）洗涤后， 用无水硫酸镁干燥，浓縮后得 2.10克 3-(2- (三氟甲基)苯基) -3-羟基 -2-(2- 苯基噻唑 -5-基)丙烯腈， 黄色油， 收率 61 %。 In an ice water bath, 4-cyanomethyl-2-phenylthiazole (2.00 g, 0.010 mol), (2-(trifluoromethyl)phenyl) (1H-pyrazol-1-yl) was added to the reaction flask. Ketone (2.40 g, 0.010 mol), 20 ml of tetrahydrofuran, stirred for about 1 hour, potassium tert-butoxide (2.24 g, 0.020 mol) was added portionwise, and after the addition was completed, the reaction mixture was warmed to room temperature and allowed to react at room temperature for 6 hours. The reaction solution was poured into 100 ml of water and extracted with 100 ml of ethyl acetate. The obtained aqueous phase was acidified with concentrated hydrochloric acid to pH 2-3, extracted with 3×100 ml of ethyl acetate, and the organic phase was saturated aqueous sodium hydrogen carbonate (100) ML), saturated sodium chloride solution After washing (100 ml), dried over anhydrous magnesium sulfate and evaporated. Acrylonitrile, yellow oil, yield 61%.
(2) 化合物 3-4的合成  (2) Synthesis of compound 3-4
Figure imgf000042_0001
Figure imgf000042_0001
在冰水浴下， 向反应瓶内加入 3-(2- (三氟甲基)苯基) -3-羟基 -2-(2-苯基噻唑 -5-基)丙烯腈 ( 0.37克， 0.001摩尔）， 乙腈 10毫升， 三乙胺 （0.10克， 0.001摩尔）， 再将 2, 2-二甲基丁酰 氯 （0.13克， 0.001摩尔）滴加到反应瓶内， 滴加结束， 升温至室温搅拌反应 2小时， 反应液 倾入 50毫升水中，用乙酸乙酯 100毫升萃取，所得有机相用饱和碳酸氢钠水溶液（100毫升）、 饱和氯化钠水溶液洗涤后 （100毫升）， 用无水硫酸镁干燥， 减压浓縮后， 残余物通过柱色谱 分离 （淋洗液： 乙酸乙酯:石油醚 = 1:20)， 得到 0.14克化合物 3-4， 黄色油， 收率 22%。  3-(2-(Trifluoromethyl)phenyl)-3-hydroxy-2-(2-phenylthiazol-5-yl)acrylonitrile (0.37 g, 0.001 mol) was added to the reaction flask under ice-water bath ), 10 ml of acetonitrile, triethylamine (0.10 g, 0.001 mol), and then 2,2-dimethylbutyryl chloride (0.13 g, 0.001 mol) was added dropwise to the reaction flask, the addition was completed, and the mixture was warmed to room temperature and stirred. After the reaction was carried out for 2 hours, the reaction mixture was poured into 50 ml of water and extracted with ethyl acetate (100 ml), and the obtained organic layer was washed with saturated aqueous sodium hydrogen carbonate (100 ml) and saturated aqueous sodium chloride (100 ml) The residue was purified by column chromatography (eluent: ethyl acetate: petroleum ether = 1:20) to afford 0.14 g of Compound 3-4 as a yellow oil.
(3)  (3)
Figure imgf000042_0002
Figure imgf000042_0002
向反应瓶内加入 3-(2- (三氟甲基)苯基) -3-羟基 -2-(2-苯基噻唑 -5-基)丙烯腈（0.74克， 0.002 摩尔）， 碳酸氢钠 （0.17克， 0.002摩尔）， 甲苯 20毫升， 4-二甲氨基吡啶 (催化量)， 四丁基 溴化铵 (催化量)， 升温至 100°C， 再将 2, 2-二甲基丁酰氯 （0.26克， 0.002摩尔） 滴加到反应 瓶内， 滴加结束， 继续反应 2小时。 反应液降温至 30°C以下， 反应液倾入 50毫升水中， 用 乙酸乙酯 100毫升萃取， 所得有机相用饱和碳酸氢钠水溶液 （100毫升）、 饱和氯化钠水溶液 洗涤后 （100毫升）， 用无水硫酸镁干燥， 减压浓縮后， 残余物通过柱色谱分离 （淋洗液： 乙 酸乙酯:石油醚 = 1:30)， 得到 0.25克化合物 3-5， 白色固体， 收率 39%。  To the reaction flask was added 3-(2-(trifluoromethyl)phenyl)-3-hydroxy-2-(2-phenylthiazol-5-yl)acrylonitrile (0.74 g, 0.002 mol), sodium bicarbonate (0.17 g, 0.002 mol), toluene 20 ml, 4-dimethylaminopyridine (catalytic amount), tetrabutylammonium bromide (catalytic amount), warmed to 100 ° C, then 2,2-dimethylbutyl The acid chloride (0.26 g, 0.002 mol) was added dropwise to the reaction flask, and the dropwise addition was completed, and the reaction was continued for 2 hours. The reaction mixture was cooled to 30 ° C or less, and the reaction mixture was poured into 50 ml of water and extracted with ethyl acetate (100 ml). The obtained organic layer was washed with saturated aqueous sodium hydrogen carbonate (100 ml) and saturated aqueous sodium chloride (100 ml) Drying over anhydrous magnesium sulfate, EtOAc (EtOAc m.) 39%.
实施例 4、 化合物 1-132的制备  Example 4 Preparation of Compound 1-132
(1) 4-氯甲基 -2-(2, 6-二氟苯基)噁唑的制备  (1) Preparation of 4-chloromethyl-2-(2,6-difluorophenyl)oxazole
Figure imgf000042_0003
Figure imgf000042_0003
向 100毫升圆底烧瓶中加入 2, 6-二氟苯甲酰胺 （10.00克， 0.064摩尔） 和 1,3-二氯丙酮 ( 16.20克， 0.128摩尔）， 升温至回流并保持反应在回流条件下进行 4小时。 停止反应后， 自 然冷却至室温， 倾入 500毫升水中， 用 3x100毫升乙酸乙酯萃取， 有机相经 3x100毫升饱和 氯化钠水溶液洗涤后， 用无水硫酸镁干燥， 浓縮后柱色谱分离 （淋洗液： 乙酸乙酯:石油醚 = 1:3) 得到 11.50克 4-氯甲基 -2-(2, 6-二氟苯基)噁唑， 黄色固体， 收率 76%。Add 2,6-difluorobenzamide (10.00 g, 0.064 mol) and 1,3-dichloroacetone (16.20 g, 0.128 mol) to a 100 mL round bottom flask, warm to reflux and keep the reaction under reflux Take 4 hours. After stopping the reaction, since After cooling to room temperature, it was poured into 500 ml of water, extracted with 3×100 ml of ethyl acetate. The organic phase was washed with 3×100 ml of saturated aqueous sodium chloride and dried over anhydrous magnesium sulfate. Ethyl acetate: petroleum ether = 1:3) 11.50 g of 4-chloromethyl-2-(2,6-difluorophenyl)oxazole as a yellow solid, yield 76%.
2) 2-(2, 6-二氟苯基) -4-氰甲基噁唑的制备  2) Preparation of 2-(2,6-difluorophenyl)-4-cyanomethyloxazole
Figure imgf000043_0001
Figure imgf000043_0001
室温下 50毫升圆底烧瓶中加入 4-氯甲基 -2-(2, 6-二氟苯基)噁唑 （20.00克， 0.087摩尔）， 加入乙醇 50毫升充分溶解， 加入氰化钠 （5.10克， 0.105摩尔）， 升温至回流并保持反应在回 流条件下进行 4小时。 停止反应后， 自然冷却至室温， 倾入 100毫升水中， 用 3x30毫升乙酸 乙酯萃取， 有机相经 3x50毫升饱和氯化钠水溶液洗涤后， 用无水硫酸镁干燥， 浓縮后柱色谱 分离 （淋洗液： 乙酸乙酯:石油醚 = 1:1 ) 得 14.60克 2-(2, 6-二氟苯基) -4-氰甲基噁唑， 白色固 体， 收率 76%。  4-chloromethyl-2-(2,6-difluorophenyl)oxazole (20.00 g, 0.087 mol) was added to a 50 ml round bottom flask at room temperature, dissolved in 50 ml of ethanol, and sodium cyanide (5.10) was added. Gram, 0.105 mol), warmed to reflux and the reaction was maintained at reflux for 4 h. After the reaction was stopped, it was cooled to room temperature, poured into 100 ml of water, and extracted with 3×30 ml of ethyl acetate. The organic phase was washed with 3×50 ml of saturated aqueous sodium chloride and dried over anhydrous magnesium sulfate. Eluent: ethyl acetate: petroleum ether = 1:1) yielded 14.60 g of 2-(2,6-difluorophenyl)-4-cyanomethyloxazole as a white solid, yield 76%.
(3 3-羟基 -3-(2-氯 -4-甲基噻唑 -5-基) -2-(2-(2, 6-二氟苯基)噁唑 -4-基)丙烯腈的制备  Preparation of (3 3-hydroxy-3-(2-chloro-4-methylthiazol-5-yl)-2-(2-(2,6-difluorophenyl)oxazol-4-yl)acrylonitrile
Figure imgf000043_0002
Figure imgf000043_0002
在冰水浴下， 向 100毫升反应瓶内加入 2-(2, 6-二氟苯基) -4-氰甲基噁唑 （2.00克， 0.009 摩尔） ， 无水四氢呋喃 25毫升， （2-氯 -4-甲基噻唑 -5-基) (1H-吡唑小基)甲酮 （2.50克， 0.011 摩尔） ， 再将叔丁醇钾 （2.30克， 0.018摩尔）少量多次地加入到反应瓶内， 升温至室温搅拌 反应 4小时， 将反应液倾入 50毫升水中， 用乙酸乙酯 2x20毫升洗涤， 弃去有机相。 将水相 用盐酸调节体系 pH=2〜3， 析出固体， 过滤晾干得到 2.00克中间体 3-羟基 -3-(2-氯 -4-甲基噻 唑 -5-基) -2-(2-(2, 6-二氟苯基)噁唑 -4-基)丙烯腈， 黄色固体， 收率 58%。  To a 100 ml reaction flask was added 2-(2,6-difluorophenyl)-4-cyanomethyloxazole (2.00 g, 0.009 mol) in anhydrous water bath, 25 ml of anhydrous tetrahydrofuran, (2-chloro 4-methylthiazole-5-yl) (1H-pyrazole small) ketone (2.50 g, 0.011 mol), then potassium t-butoxide (2.30 g, 0.018 mol) was added in small portions to the reaction flask. The mixture was heated to room temperature and stirred for 4 hours. The reaction mixture was poured into 50 ml of water and washed with ethyl acetate 2x 20 ml, and the organic phase was discarded. The aqueous phase was adjusted to pH 2 to 3 with hydrochloric acid to precipitate a solid, which was filtered and dried to give 2.00 g of intermediate 3-hydroxy-3-(2-chloro-4-methylthiazol-5-yl)-2-(2) -(2,6-Difluorophenyl)oxazol-4-yl)acrylonitrile, yellow solid, yield 58%.
(4 化合物 1-132的制备  (4 Preparation of Compound 1-132
Figure imgf000043_0003
Figure imgf000043_0003
在冰水浴下， 向 50毫升反应瓶内依次加入 3-羟基 -3-(2-氯 -4-甲基噻唑 -5-基) -2-(2-(2, 6-二 氟苯基)噁唑 -4-基)丙烯腈 (0.30克， 0.001摩尔) ， 乙腈 15毫升和三乙胺 （0.10克， 0.001摩 尔）， 再将氯甲酸甲酯（0.10克， 0.001摩尔）滴加到反应瓶内， 升温至室温搅拌反应 4小时， 反应液倾入 50毫升水中， 用乙酸乙酯萃取 （2x50毫升） ， 所得有机相用 15毫升饱和碳酸氢 钠水溶液、 25毫升饱和氯化钠水溶液洗涤后， 用无水硫酸镁干燥， 减压浓縮后， 残余物通过 柱色谱分离（淋洗液： 乙酸乙酯:石油醚 = 1:3)得到 0.20克化合物 1-132， 黄色油， 收率 51%。 实施例 5、 化合物 2-140的制备 3-Hydroxy-3-(2-chloro-4-methylthiazol-5-yl)-2-(2-(2,6-difluorophenyl) was added to a 50 ml reaction flask in an ice water bath. Oxazol-4-yl)acrylonitrile (0.30 g, 0.001 mol), acetonitrile 15 ml and triethylamine (0.10 g, 0.001 mol), then methyl chloroformate (0.10 g, 0.001 mol) was added dropwise to the reaction flask The mixture was warmed to room temperature and stirred for 4 hours. The reaction mixture was poured into 50 ml of water, and ethyl acetate (2×50 ml) was evaporated. The organic phase was washed with 15 ml of saturated aqueous sodium hydrogen carbonate and 25 ml of saturated aqueous sodium chloride. After drying over anhydrous magnesium sulfate and EtOAc (EtOAc m. . Example 5 Preparation of Compound 2-140
(1) -羟基 -3-(1-乙基 -3-甲基 -1H-吡唑 -5-基) -2-(2-(2, 6-二氟苯基)噁唑 -4-基)丙烯腈的合成  (1) -Hydroxy-3-(1-ethyl-3-methyl-1H-pyrazol-5-yl)-2-(2-(2,6-difluorophenyl)oxazol-4-yl ) Synthesis of acrylonitrile
在冰水浴下， 向 100毫升反应瓶内加入 2-(2, 6-二氟苯基) -4-氰甲基噁唑 （4.00克， 0.018 摩尔） ， 无水四氢呋喃 50毫升， （1-乙基 -3-甲基 -1H-吡唑 -5-基) (1H-吡唑小基)甲酮 （4.08克， 0.020摩尔） ， 再将叔丁醇钾 （4.07克， 0.036摩尔） 少量多次地加入到反应瓶内， 升温至室 温搅拌反应 4小时， 将反应液倾入 50毫升水中， 用乙酸乙酯 2x20毫升洗涤， 弃去有机相。 将水相用盐酸调节体系 pH=2〜3，析出固体，过滤晾干得到 5.20克中间体 3-羟基 -3-(1-乙基 -3- 甲基 -1H-吡唑 -5-基) -2-(2-(2, 6-二氟苯基)噁唑 -4-基)丙烯腈， 黄色固体， 收率 80%。  To a 100 ml reaction flask was added 2-(2,6-difluorophenyl)-4-cyanomethyloxazole (4.00 g, 0.018 mol) in an ice-water bath, anhydrous tetrahydrofuran 50 ml, (1-B 3-methyl-1H-pyrazol-5-yl) (1H-pyrazole small) ketone (4.08 g, 0.020 mol), then potassium t-butoxide (4.07 g, 0.036 mol) The mixture was poured into a reaction flask, and the mixture was warmed to room temperature and stirred for 4 hours. The reaction mixture was poured into 50 ml of water, and washed with ethyl acetate 2×20 ml, and the organic phase was discarded. The aqueous phase was adjusted to pH 2 to 3 with hydrochloric acid to precipitate a solid, which was filtered and dried to give 5.20 g of intermediate 3-hydroxy-3-(1-ethyl-3-methyl-1H-pyrazol-5-yl) 2-(2-(2,6-Difluorophenyl)oxazol-4-yl)acrylonitrile, yellow solid, yield 80%.
(2) -140的合成  (2) Synthesis of -140
Figure imgf000044_0002
Figure imgf000044_0002
在冰水浴下，向 50毫升反应瓶内依次加入 3-羟基 -3-(1-乙基 -3-甲基 -1H-吡唑 -5-基) -2-(2-(2, 6-二氟苯基)噁唑 -4-基)丙烯腈（0.30克， 0.001摩尔)， 乙腈 15毫升和三乙胺（0.12克， 0.001 摩尔） ， 再将氯甲酸甲酯 （0.10克， 0.001摩尔）滴加到反应瓶内， 升温至室温搅拌反应 4小 时， 反应液倾入 50毫升水中， 用乙酸乙酯萃取 （2x50毫升） ， 所得有机相用 15毫升饱和碳 酸氢钠水溶液、 25毫升饱和氯化钠水溶液洗涤后， 用无水硫酸镁干燥， 减压浓縮后， 残余物 通过柱色谱分离 （淋洗液： 乙酸乙酯:石油醚 = 1:5)得到 0.25克化合物 2-140， 黄色油， 收率 67%。  In a 50 ml reaction flask, 3-hydroxy-3-(1-ethyl-3-methyl-1H-pyrazol-5-yl)-2-(2-(2, 6-) was added in an ice water bath. Difluorophenyl)oxazole-4-yl)acrylonitrile (0.30 g, 0.001 mol), acetonitrile 15 ml and triethylamine (0.12 g, 0.001 mol), then methyl chloroformate (0.10 g, 0.001 mol) The mixture was added dropwise to the reaction mixture, and the mixture was warmed to room temperature and stirred for 4 hours. The reaction mixture was poured into 50 ml of water and extracted with ethyl acetate (2×50 ml). The obtained organic phase was saturated with 15 ml of saturated aqueous sodium hydrogen carbonate After washing with a sodium aqueous solution, dried over anhydrous magnesium sulfate, and evaporated, evaporated, evaporated, evaporated, , yield 67%.
实施例 6、 化合物 2-152的制备  Example 6. Preparation of Compound 2-152
Figure imgf000044_0003
Figure imgf000044_0003
在冰水浴下，向 50毫升反应瓶内依次加入 3-羟基 -3-(1-乙基 -3-甲基 -1H-吡唑 -5-基) -2-(2-(2, 6-二氟苯基)噁唑 -4-基)丙烯腈（0.30克， 0.001摩尔)， 乙腈 15毫升和三乙胺（0.10克， 0.001 摩尔） ， 再将氯甲酸甲酯 （0.10克， 0.001摩尔）滴加到反应瓶内， 升温至室温搅拌反应 4小 时， 反应液倾入 50毫升水中， 用乙酸乙酯萃取 （2x50毫升） ， 所得有机相用 15毫升饱和碳 酸氢钠水溶液、 25毫升饱和氯化钠水溶液洗涤后， 用无水硫酸镁干燥， 减压浓縮后， 残余物 通过柱色谱分离 （淋洗液： 乙酸乙酯:石油醚 = 1:5)得到 0.23克化合物 2-152， 黄色油， 收率 66%。 In a 50 ml reaction flask, 3-hydroxy-3-(1-ethyl-3-methyl-1H-pyrazol-5-yl)-2-(2-(2, 6-) was added in an ice water bath. Difluorophenyl)oxazole-4-yl)acrylonitrile (0.30 g, 0.001 mol), acetonitrile 15 ml and triethylamine (0.10 g, 0.001 mol), then methyl chloroformate (0.10 g, 0.001 mol) The mixture was added dropwise to the reaction mixture, and the mixture was warmed to room temperature and stirred for 4 hours. The reaction mixture was poured into 50 ml of water and extracted with ethyl acetate (2×50 ml). The obtained organic phase was saturated with 15 ml of saturated aqueous sodium hydrogen carbonate After washing with a sodium aqueous solution, it was dried over anhydrous magnesium sulfate and concentrated under reduced pressure. Separation by column chromatography (eluent: ethyl acetate: petroleum ether = 1:5) afforded 0.23 g of Compound 2-152 as a yellow oil.
实施例 7、 化合物 2-287的制备  Example 7. Preparation of Compound 2-287
(1) 3-羟基 -3-(4-氯 -1-乙基 -3-甲基吡唑 -5-基) -2-(2-(2, 6-二 -4-基)丙烯腈的合成  (1) 3-Hydroxy-3-(4-chloro-1-ethyl-3-methylpyrazol-5-yl)-2-(2-(2,6-di-4-yl)acrylonitrile Synthesis
Figure imgf000045_0001
Figure imgf000045_0001
在冰水浴下， 向 100毫升反应瓶内加入 2-(2, 6-二氟苯基) -4-氰甲基噁唑 （4.00克， 0.018 摩尔） ， 无水四氢呋喃 50毫升， （4-氯小乙基 -3-甲基 -1H-吡唑 -5-基) (1H-吡唑小基)甲酮（4.77 克， 0.020摩尔） ， 再将叔丁醇钾 （4.07克， 0.036摩尔） 少量多次地加入到反应瓶内， 升温 至室温搅拌反应 4小时， 将反应液倾入 50毫升水中， 用乙酸乙酯 2x20毫升洗涤， 弃去有机 相。 将水相用盐酸调节体系 pH=2〜3， 析出固体， 过滤晾干得到 5.77克中间体 3-羟基 -3-(4- 氯 -1-乙基 -3-甲基 -1H-吡唑 -5-基) -2-(2-(2, 6-二氟苯基)噁唑 -4-基)丙烯腈，黄色固体，收率 82%。  To a 100 ml reaction flask was added 2-(2,6-difluorophenyl)-4-cyanomethyloxazole (4.00 g, 0.018 mol) in an ice-water bath, anhydrous tetrahydrofuran 50 ml, (4-chloro Small ethyl-3-methyl-1H-pyrazol-5-yl) (1H-pyrazole small) ketone (4.77 g, 0.020 mol), then potassium tert-butoxide (4.07 g, 0.036 mol) It was added to the reaction flask several times, and the mixture was warmed to room temperature and stirred for 4 hours. The reaction mixture was poured into 50 ml of water and washed with ethyl acetate 2×20 ml, and the organic phase was discarded. The aqueous phase was adjusted to pH 2 to 3 with hydrochloric acid, and the solid was precipitated, which was filtered and dried to give 5.77 g of intermediate 3-hydroxy-3-(4-chloro-1-ethyl-3-methyl-1H-pyrazole- 5-yl)-2-(2-(2,6-difluorophenyl)oxazol-4-yl)acrylonitrile, yellow solid, yield 82%.
(2) 化合物 2-287的合成  (2) Synthesis of compound 2-287
Figure imgf000045_0002
Figure imgf000045_0002
在冰水浴下， 向 50 毫升反应瓶内依次加入 3-羟基 -3-(4-氯 -1-乙基 -3-甲基 -1H-B比唑 -5- 基) -2-(2-(2, 6-二氟苯基)噁唑 -4-基)丙烯腈（0.30克， 0.001摩尔）， 乙腈 15毫升和三乙胺（0.12 克， 0.001摩尔） ， 再将 3-氯 -2, 2-二甲基丙酰氯 （0.15克， 0.001摩尔） 滴加到反应瓶内， 升 温至室温搅拌反应 4小时， 反应液倾入 50毫升水中， 用乙酸乙酯萃取 （2x50毫升） ， 所得 有机相用 15毫升饱和碳酸氢钠水溶液、 25毫升饱和氯化钠水溶液洗涤后， 用无水硫酸镁干 燥， 减压浓縮后， 残余物通过柱色谱分离 （淋洗液： 乙酸乙酯:石油醚 = 1:5) 得到 0.33克化 合物 2-287， 黄色油， 收率 85%。  3-Hydroxy-3-(4-chloro-1-ethyl-3-methyl-1H-Bbiazole-5-yl)-2-(2-) was added to a 50 ml reaction flask in an ice water bath. (2,6-Difluorophenyl)oxazol-4-yl)acrylonitrile (0.30 g, 0.001 mol), acetonitrile 15 ml and triethylamine (0.12 g, 0.001 mol), then 3-chloro-2, 2-Dimethylpropanoyl chloride (0.15 g, 0.001 mol) was added dropwise to the reaction flask, and the mixture was warmed to room temperature and stirred for 4 hours. The reaction mixture was poured into 50 ml of water and extracted with ethyl acetate (2×50 ml). After washing with 15 ml of a saturated aqueous solution of sodium hydrogencarbonate and brine (25 ml of saturated aqueous sodium chloride), dried over anhydrous magnesium sulfate and evaporated. 1:5) 0.33 g of compound 2-287, yellow oil, yield 85%.
实施例 8、 化合物 3-122的制备  Example 8. Preparation of Compound 3-122
(1) 3-羟基 -3-(2-三氟甲基苯基 )-2-(2-(2, 6-二氟苯基)噁唑 -4-  (1) 3-Hydroxy-3-(2-trifluoromethylphenyl)-2-(2-(2,6-difluorophenyl)oxazole-4-
Figure imgf000045_0003
Figure imgf000045_0003
在冰水浴下， 向 100毫升反应瓶内加入 2-(2, 6-二氟苯基) -4-氰甲基噁唑 （2.00克， 0.009 摩尔）， 无水四氢呋喃 25毫升， (2-三氟甲基苯基 )(1Η-吡唑小基)甲酮 (2.60克， 0.011摩尔）， 再将叔丁醇钾（2.30克， 0.018摩尔）少量多次地加入到反应瓶内， 升温至室温搅拌反应 4小 时， 将反应液倾入 50毫升水中， 用乙酸乙酯 2x20毫升洗涤， 弃去有机相。 将水相用盐酸调 节体系 pH=2〜3， 析出固体， 过滤晾干得到 2.00克 3-羟基 -3-(2-三氟甲基苯基 )-2-(2-(2, 6-二氟 苯基)噁唑 -4-基)丙烯腈， 黄色固体， 收率 67%。 To a 100 ml reaction flask was added 2-(2,6-difluorophenyl)-4-cyanomethyloxazole (2.00 g, 0.009 mol) in an ice-water bath, anhydrous tetrahydrofuran 25 ml, (2-three Fluoromethylphenyl) (1Η-pyrazole small) ketone (2.60 g, 0.011 mol), potassium tert-butoxide (2.30 g, 0.018 mol) was added to the reaction flask in small portions, and the temperature was raised to room temperature. Stirring reaction 4 small The reaction solution was poured into 50 ml of water, washed with ethyl acetate (2×20 ml), and the organic phase was discarded. The aqueous phase was adjusted to pH 2 to 3 with hydrochloric acid to precipitate a solid, which was filtered and dried to give 2.00 g of 3-hydroxy-3-(2-trifluoromethylphenyl)-2-(2-(2, 6-) Fluorophenyl)oxazole-4-yl)acrylonitrile, yellow solid, yield 67%.
(2) -122的合成  (2) Synthesis of -122
Figure imgf000046_0001
Figure imgf000046_0001
在冰水浴下， 向 50毫升反应瓶内依次加入 3-羟基 -3-(2-三氟甲基苯基 )-2-(2-(2, 6-二氟苯 基)噁唑—4-基)丙烯腈 (0.30克， 0.001摩尔）， 乙腈 15毫升和三乙胺 （0.10克， 0.001摩尔）， 再将氯甲酸甲酯（0.10克， 0.001摩尔）滴加到反应瓶内， 升温至室温搅拌反应 4小时， 反应 液倾入 50毫升水中， 用乙酸乙酯萃取 （2x50毫升）， 所得有机相用 15毫升饱和碳酸氢钠水 溶液、 25毫升饱和氯化钠水溶液洗涤后， 用无水硫酸镁干燥， 减压浓縮后， 残余物通过柱色 谱分离 （淋洗液： 乙酸乙酯:石油醚 = 1:3) 得到 0.20克化合物 3-122， 白色固体， 收率 56%。  3-Hydroxy-3-(2-trifluoromethylphenyl)-2-(2-(2,6-difluorophenyl)oxazole-4 was added to a 50 ml reaction flask in an ice water bath. Acrylonitrile (0.30 g, 0.001 mol), 15 ml of acetonitrile and triethylamine (0.10 g, 0.001 mol), and then methyl chloroformate (0.10 g, 0.001 mol) was added dropwise to the reaction flask and allowed to warm to room temperature. The reaction was stirred for 4 hours, and the reaction mixture was poured into 50 ml of water, and ethyl acetate (2×50 ml) was obtained, and the obtained organic phase was washed with 15 ml of saturated aqueous sodium hydrogen carbonate and 25 ml of saturated aqueous sodium chloride After drying and concentrating under reduced pressure, the residue was evaporated. mjjjjjjj
实施例 9、 化合物 1-158的制备  Example 9. Preparation of Compound 1-158
(1) 3-甲基 -1-苯基 -1H-吡唑的制备
Figure imgf000046_0002
(1) Preparation of 3-methyl-1-phenyl-1H-pyrazole
Figure imgf000046_0002
向反应瓶内加入苯肼 （5.00克， 0.046摩尔） ， 4, 4-二甲氧基 -2-丁酮 （7.30克， 0.055摩 尔)) ， 乙醇 40毫升， 升温至回流， 回流 2小时。 向反应液中滴加浓盐酸 （0.5毫升） ， 继续 回流 2小时。 反应结束后降温至 30°C以下， 反应液倾入 200毫升水中， 用 3x150毫升乙酸乙 酯萃取， 所得有机相用饱和氯化钠水溶液 （150 毫升） 洗涤后， 用无水硫酸镁干燥， 减压浓 縮后，残余物通过柱色谱分离（淋洗液：乙酸乙酯:石油醚 = 1:10)得 5.00克 3-甲基 -1-苯基 -1H- 吡唑， 黄色油， 收率 68 %。  To the reaction flask were placed phenylhydrazine (5.00 g, 0.046 mol), 4,4-dimethoxy-2-butanone (7.30 g, 0.055 mol), and 40 ml of ethanol, which was warmed to reflux and refluxed for 2 hr. Concentrated hydrochloric acid (0.5 ml) was added dropwise to the reaction mixture, and reflux was continued for 2 hr. After the completion of the reaction, the temperature was lowered to 30 ° C or less, and the reaction mixture was poured into 200 ml of water and extracted with 3×150 ml of ethyl acetate. The obtained organic layer was washed with saturated aqueous sodium chloride (150 ml) and dried over anhydrous magnesium sulfate. After concentration by pressure, the residue was purified by column chromatography (eluent: ethyl acetate: petroleum ether = 1:10) to give 5.00 g of 3-methyl-1-phenyl-1H-pyrazole, yellow oil, yield 68%.
(2) 3-溴甲基
Figure imgf000046_0003
(2) 3-bromomethyl
Figure imgf000046_0003
向反应瓶内加入 3-甲基小苯基 -1H-吡唑 （0.50克， 0.003摩尔） ， 甲苯 5毫升， 升温至 70°C， 向反应液加入 N-溴代丁二酰亚胺 （0.40克， 0.003摩尔） ， 偶氮二异丁腈 (催化量)， 加 毕， 反应液升温至回流， 回流反应 1小时。 反应结束后降温至 30°C以下， 反应液倾入 50毫 升水中， 用 3x50毫升乙酸乙酯萃取， 所得有机相用饱和碳酸氢钠水溶液 （50毫升） 、 饱和 氯化钠水溶液 （50毫升） 洗涤后， 用无水硫酸镁干燥， 减压浓縮后， 残余物通过柱色谱分离 (淋洗液:乙酸乙酯:石油醚 = 1:100)得 0.40克 3-溴甲基小苯基 -1H-吡唑，黄色油，收率 56% (3) 2-(1-苯基 -1H-吡唑 -3-基)乙腈的制备
Figure imgf000047_0001
3-methylphenylidene-1H-pyrazole (0.50 g, 0.003 mol), toluene 5 ml was added to the reaction flask, and the temperature was raised to 70 ° C, and N-bromosuccinimide (0.40) was added to the reaction mixture. Gram, 0.003 mol), azobisisobutyronitrile (catalytic amount), after the addition, the reaction solution was heated to reflux and refluxed for 1 hour. After the completion of the reaction, the temperature was lowered to 30 ° C or less, and the reaction mixture was poured into 50 ml of water and extracted with 3×50 ml of ethyl acetate. The obtained organic layer was washed with saturated aqueous sodium hydrogen sulfate (50 ml) and saturated aqueous sodium chloride (50 ml) After drying over anhydrous magnesium sulfate and concentrating under reduced pressure, the residue was purified by column chromatography (eluent: ethyl acetate: petroleum ether = 1:100) to give 0.40 g of 3-bromomethyl phenyl-1H. -pyrazole, yellow oil, yield 56% (3) Preparation of 2-(1-phenyl-1H-pyrazol-3-yl)acetonitrile
Figure imgf000047_0001
向反应瓶内加入 3-溴甲基 -1-苯基 -1H-吡唑 （0.55克， 0.003摩尔) ， 二甲基亚砜 5毫升， 氰化钠 （0.15克， 0.003摩尔） ， 室温反应 6小时。 反应结束后将反应液倾入 100毫升水中， 用 3x100毫升乙酸乙酯萃取， 所得有机相用饱和氯化钠水溶液 （100毫升） 洗涤后， 用无水 硫酸镁干燥， 减压浓縮后， 残余物通过柱色谱分离（淋洗液： 乙酸乙酯:石油醚 = 1:20)得 0.20 克 2-(1-苯基 -1H-吡唑 -3-基)乙腈， 黄色油， 收率 36%。  3-bromomethyl-1-phenyl-1H-pyrazole (0.55 g, 0.003 mol), dimethyl sulfoxide 5 ml, sodium cyanide (0.15 g, 0.003 mol) were added to the reaction flask. hour. After the completion of the reaction, the reaction mixture was poured into water (100 ml), EtOAc (EtOAc) Separation by column chromatography (eluent: ethyl acetate: petroleum ether = 1:20) afforded 0.20 g of 2-(1-phenyl-1H-pyrazol-3-yl)acetonitrile as a yellow oil, yield 36% .
(4) 3-羟基 -3-(2-氯 -4-甲基噻唑 -5-基) -2-(1-苯基吡唑 -3-基)丙烯腈的制备
Figure imgf000047_0002
(4) Preparation of 3-hydroxy-3-(2-chloro-4-methylthiazol-5-yl)-2-(1-phenylpyrazol-3-yl)acrylonitrile
Figure imgf000047_0002
在冰水浴下， 向 50毫升反应瓶内加入 1-苯基 -3-氰甲基 -1H-吡唑（0.80克， 0.004摩尔）， 无水四氢呋喃 25毫升， （2-氯 -4-甲基噻唑 -5-基) (1H-吡唑小基)甲酮 （1.20克， 0.005摩尔) ， 再将叔丁醇钾 （1.00克， 0.09摩尔） 少量多次地加入到反应瓶内， 升温至室温搅拌反应 4小 时， 将反应液倾入 50毫升水中， 用乙酸乙酯 2x20毫升洗涤， 弃去有机相。 将水相用盐酸调 节体系 pH=2〜3， 析出固体， 过滤晾干得到 0.90 克中间体 3-羟基 -3-(2-氯 -4-甲基噻唑 -5- 基) -2-(1-苯基吡唑 -3-基)丙烯腈， 黄色固体， 收率 60%。  In a 50 ml reaction flask, 1-phenyl-3-cyanomethyl-1H-pyrazole (0.80 g, 0.004 mol), anhydrous tetrahydrofuran 25 ml, (2-chloro-4-methyl) Thiazol-5-yl) (1H-pyrazole small) ketone (1.20 g, 0.005 mol), then potassium t-butoxide (1.00 g, 0.09 mol) was added in small portions to the reaction flask and allowed to warm to room temperature. The reaction was stirred for 4 hours, and the reaction mixture was poured into 50 ml of water, washed with ethyl acetate 2x 20 ml, and the organic phase was discarded. The aqueous phase was adjusted to pH 2 to 3 with hydrochloric acid to precipitate a solid, which was filtered and dried to give <RTI ID=0.0>> -Phenylpyrazol-3-yl)acrylonitrile, yellow solid, yield 60%.
(5) 化合物 1-158的制备  (5) Preparation of compound 1-158
Figure imgf000047_0003
Figure imgf000047_0003
在冰水浴下， 向 50毫升反应瓶内依次加入 3-羟基 -3-(2-氯 -4-甲基噻唑 -5-基) -2-(1-苯基吡 唑 -3-基)丙烯腈 （0.30克， 0.001摩尔） ， 乙腈 15毫升和三乙胺 （0.11克， 0.001摩尔） ， 再 将特戊酰氯（0.12克， 0.001摩尔）滴加到反应瓶内， 升温至室温搅拌反应 4小时， 反应液倾 入 50毫升水中， 用乙酸乙酯萃取（2x50毫升）， 所得有机相用 15毫升饱和碳酸氢钠水溶液、 25毫升饱和氯化钠水溶液洗涤后， 用无水硫酸镁干燥， 减压浓縮后， 残余物通过柱色谱分离 (淋洗液： 乙酸乙酯:石油醚 = 1:5) 得到 0.15克化合物 1-158， 黄色油， 收率 44%。  3-Hydroxy-3-(2-chloro-4-methylthiazol-5-yl)-2-(1-phenylpyrazol-3-yl)propene was added to a 50 ml reaction flask in an ice water bath. Nitrile (0.30 g, 0.001 mol), acetonitrile 15 ml and triethylamine (0.11 g, 0.001 mol), then pivaloyl chloride (0.12 g, 0.001 mol) was added dropwise to the reaction flask, and the mixture was warmed to room temperature and stirred for 4 hours. The reaction mixture was poured into 50 ml of water and extracted with ethyl acetate (2×50 ml). The obtained organic layer was washed with 15 ml of aq. After concentration, the residue was purified by column chromatography (EtOAc:EtOAc:EtOAc:EtOAc)
实施例 10、 化合物 2-198的制备  Example 10 Preparation of Compound 2-198
(1) 3-羟基 -3-(1-乙基 -3-
Figure imgf000047_0004
在冰水浴下， 向 50毫升反应瓶内加入 1-苯基 -3-氰甲基 -1H-吡唑（0.92克， 0.005摩尔）， 无水四氢呋喃 25毫升， （1-乙基 -3-甲基 -1H-吡唑 -5-基) (1H-吡唑小基)甲酮 （1.02克， 0.005摩 尔） ， 再将叔丁醇钾 （1.12克， 0.010摩尔） 少量多次地加入到反应瓶内， 升温至室温搅拌反 应 4小时， 将反应液倾入 50毫升水中， 用乙酸乙酯 2x20毫升洗涤， 弃去有机相。 将水相用 盐酸调节体系 pH=2〜3， 再用乙酸乙酯 3x25毫升充分萃取， 用无水硫酸镁干燥， 减压浓縮得 到 0.96克中间体 3-(1-乙基 -3-甲基 -1H-吡唑 -5-基) -3-羟基 -2-(2-甲基小苯基 -1H-吡唑 -3-基)丙烯 腈， 黄色油， 收率 60%。 (1) 3-hydroxy-3-(1-ethyl-3-
Figure imgf000047_0004
In a 50 ml reaction flask, 1-phenyl-3-cyanomethyl-1H-pyrazole (0.92 g, 0.005 mol), anhydrous tetrahydrofuran 25 ml, (1-ethyl-3-methyl) -1-1H-pyrazol-5-yl) (1H-pyrazole small) ketone (1.02 g, 0.005 mol), then potassium t-butoxide (1.12 g, 0.010 mol) was added in small portions to the reaction flask The mixture was heated to room temperature and stirred for 4 hours. The reaction mixture was poured into 50 ml of water and washed with ethyl acetate 2x 20 ml, and the organic phase was discarded. The aqueous phase was adjusted to pH 2 to 3 with hydrochloric acid, and then extracted with ethyl acetate (3×25 ml), dried over anhydrous magnesium sulfate. -1H-pyrazol-5-yl)-3-hydroxy-2-(2-methylphenylphenyl-1H-pyrazol-3-yl)acrylonitrile, yellow oil, yield 60%.
(2)  (2)
Figure imgf000048_0001
Figure imgf000048_0001
在冰水浴下， 向反应瓶内加入 3-(1-乙基 -3-甲基 -1H-吡唑 -5-基) -3-羟基 -2-(2-甲基 -1-苯基 In the ice water bath, 3-(1-ethyl-3-methyl-1H-pyrazole-5-yl)-3-hydroxy-2-(2-methyl-1-phenyl) was added to the reaction flask.
-1H-吡唑 -3-基)丙烯腈（0.30克， 0.001摩尔）， 乙腈 20毫升， 三乙胺 (0.11克， 0.001摩尔）， 再将氯甲酸甲酯 （0.09克， 0.001摩尔） 滴加到反应瓶内， 滴加结束， 升温至室温搅拌反应 4 小时， 反应液倾入 50毫升水中， 用乙酸乙酯萃取 （2x50毫升） ， 所得有机相用 15毫升饱和 碳酸氢钠水溶液、 25毫升饱和氯化钠水溶液洗涤后， 用无水硫酸镁干燥， 减压浓縮后， 残余 物通过柱色谱分离（淋洗液： 乙酸乙酯:石油醚 = 1:5)得到 0.15克化合物 2-198为一组立体异 构体混合物 （Z:E=1:6) ， 黄色油， 收率 45%。 -1H-pyrazol-3-yl)acrylonitrile (0.30 g, 0.001 mol), acetonitrile 20 ml, triethylamine (0.11 g, 0.001 mol), then methyl chloroformate (0.09 g, 0.001 mol) was added dropwise Into the reaction flask, the dropwise addition was completed, and the mixture was warmed to room temperature and stirred for 4 hours. The reaction mixture was poured into 50 ml of water and extracted with ethyl acetate (2×50 ml). The obtained organic phase was saturated with 15 ml of saturated aqueous sodium hydrogencarbonate and 25 ml. After washing with an aqueous solution of sodium chloride, dried over anhydrous magnesium sulfate, and evaporated, evaporated, evaporated. A mixture of stereoisomers (Z: E = 1:6), yellow oil, yield 45%.
实施例 11、 化合物 3-144的制备  Example 11, Preparation of Compound 3-144
(1) 3-(2- -2-(1-苯基 -1H-吡唑 -3-基) -3-羟基丙烯腈的合成  (1) Synthesis of 3-(2- -2-(1-phenyl-1H-pyrazol-3-yl)-3-hydroxyacrylonitrile
Figure imgf000048_0002
Figure imgf000048_0002
在冰水浴下， 向反应瓶内加入 3-氰甲基 -1-苯基 -1H-吡唑 （0.50克， 0.003摩尔）， （2-三氟 甲基苯基) (1H-吡唑小基)甲酮 （0.96克， 0.004摩尔）， 四氢呋喃 5毫升， 搅拌约 1小时， 分 批加入叔丁醇钾 （0.67克， 0.006摩尔）， 加料结束， 反应液升温至室温， 室温反应 6小时。 反应液倾入 100毫升水中，用 100毫升乙酸乙酯萃取，所得水相用浓盐酸调酸至 pH值为 2~3， 用 3x100毫升乙酸乙酯萃取， 有机相经饱和碳酸氢钠水溶液 （100毫升）、 饱和氯化钠水溶液 ( 100毫升）洗涤后，用无水硫酸镁干燥，浓縮后得 0.90克 3-(2-三氟甲基苯基 )-2-(1-苯基 -1H- 吡唑 -3-基) -3-羟基丙烯腈， 黄色固体， 收率 85 %， 熔点： 118-120°C。  In an ice water bath, 3-cyanomethyl-1-phenyl-1H-pyrazole (0.50 g, 0.003 mol), (2-trifluoromethylphenyl) (1H-pyrazole small group) was added to the reaction flask. Ketone (0.96 g, 0.004 mol), 5 ml of tetrahydrofuran, stirred for about 1 hour, potassium tert-butoxide (0.67 g, 0.006 mol) was added portionwise, and after the addition was completed, the reaction mixture was warmed to room temperature and allowed to react at room temperature for 6 hours. The reaction mixture was poured into 100 ml of water and extracted with 100 ml of ethyl acetate. The obtained aqueous phase was acidified with concentrated hydrochloric acid to pH 2-3, extracted with 3×100 ml of ethyl acetate After washing with a saturated aqueous solution of sodium chloride (100 ml), dried over anhydrous magnesium sulfate - pyrazol-3-yl)-3-hydroxyacrylonitrile, yellow solid, yield 85%, m.p.: 118-120.
(2) 化合物 3-144的合成
Figure imgf000049_0001
(2) Synthesis of compound 3-144
Figure imgf000049_0001
在冰水浴下，向反应瓶内加入 3-(2-三氟甲基苯基 )-2-(1-苯基 -1H-吡唑 -3-基) -3-羟基丙烯腈 (0.36克， 0.001摩尔）， 乙腈 5毫升， 三乙胺 （0.10克， 0.001摩尔）， 再将新戊酰氯 (0.12 克， 0.001摩尔） 滴加到反应瓶内， 滴加结束， 升温至室温搅拌反应 2小时， 反应液倾入 50 毫升水中， 用乙酸乙酯 3x100毫升萃取， 所得有机相用饱和碳酸氢钠水溶液 （100毫升）、 饱 和氯化钠水溶液洗涤后 （100毫升）， 用无水硫酸镁干燥， 减压浓縮后， 残余物通过柱色谱分 离 （淋洗液： 乙酸乙酯:石油醚 = 1:15)， 得到 0.30克化合物 3-144， 黄色油， 收率 68%。  3-(2-Trifluoromethylphenyl)-2-(1-phenyl-1H-pyrazol-3-yl)-3-hydroxyacrylonitrile (0.36 g, was added to the reaction flask under ice-water bath. 0.001 mol), acetonitrile 5 ml, triethylamine (0.10 g, 0.001 mol), p-pivaloyl chloride (0.12 g, 0.001 mol) was added dropwise to the reaction flask, the dropwise addition was completed, and the mixture was warmed to room temperature and stirred for 2 hours. The reaction mixture was poured into 50 ml of water and extracted with ethyl acetate (3×100 ml). The obtained organic layer was washed with saturated aqueous sodium hydrogen carbonate (100 ml) and saturated aqueous sodium chloride (100 ml) After concentration by pressure, the residue was purified by column chromatography (EtOAc:EtOAc:EtOAc:EtOAc)
实施例 1 -156的制备  Example 1 - 156 Preparation
Figure imgf000049_0002
Figure imgf000049_0002
在冰水浴下，向反应瓶内加入 3-(2-三氟甲基苯基 )-2-(1-苯基 -1H-吡唑 -3-基) -3-羟基丙烯腈 In the ice water bath, 3-(2-trifluoromethylphenyl)-2-(1-phenyl-1H-pyrazol-3-yl)-3-hydroxyacrylonitrile was added to the reaction flask.
(0.36克， 0.001摩尔）， 乙腈 5毫升， 三乙胺（0.10克， 0.001摩尔）， 再将氯甲酸乙酯 (0.11 克， 0.001摩尔） 滴加到反应瓶内， 滴加结束， 升温至室温搅拌反应 2小时， 反应液倾入 50 毫升水中， 用乙酸乙酯 3x100毫升萃取， 所得有机相用饱和碳酸氢钠水溶液 （100毫升）、 饱 和氯化钠水溶液洗涤后 （100毫升）， 用无水硫酸镁干燥， 减压浓縮后， 残余物通过柱色谱分 离 （淋洗液： 乙酸乙酯:石油醚 = 1:15)， 得到 0.21克化合物 3-156， 为一组立体异构体混合物 (Z:E=1:2)， 黄色油， 收率 49%。 (0.36 g, 0.001 mol), acetonitrile 5 ml, triethylamine (0.10 g, 0.001 mol), then ethyl chloroformate (0.11 g, 0.001 mol) was added dropwise to the reaction flask, the addition was completed, and the temperature was raised to room temperature. The reaction was stirred for 2 hours, and the reaction mixture was poured into 50 ml of EtOAc (EtOAc)EtOAc. After drying over magnesium sulfate and concentrating under reduced pressure, the residue was purified by column chromatography (eluent: ethyl acetate: petroleum ether = 1:15) to give 0.21 g of compound 3-156 as a mixture of stereoisomers ( Z: E = 1: 2), yellow oil, yield 49%.
生物活性测定  Biological activity assay
根据待测化合物的溶解性， 原药用丙酮或二甲亚砜溶解， 然后用 1%。的吐温 80溶液配制 成所需浓度的待测液 50毫升， 丙酮或二甲亚砜在溶液中的含量不超过 10%。 杀虫死亡率活 性分级如下： A: 100%； B: 99 -80 ； C: 79 -60 ； D: 59%-0。  Depending on the solubility of the test compound, the original pharmaceutically acceptable acetone or dimethyl sulfoxide is dissolved, and then 1% is used. The Tween 80 solution is prepared to a desired concentration of 50 ml of the test solution, and the content of acetone or dimethyl sulfoxide in the solution is not more than 10%. The insecticidal mortality activity was graded as follows: A: 100%; B: 99-80; C: 79-60; D: 59%-0.
实施例 13、 杀虫活性的测定  Example 13. Determination of insecticidal activity
13.1 杀桃蚜活性的测定  13.1 Determination of the activity of chlorpyrifos
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， 去除有翅蚜及叶片正 面的蚜虫， 调查基数后， 叶背向上置于培养皿内， 用手持式 Airbrush喷雾器进行喷雾处理， 压力为 lO psi (约合 0.7 kg/cm2)， 喷液量为 0.5 mL， 每处理 3次重复， 处理后置于标准观察室 内， 48小时后调查存活虫数， 计算死亡率并分级。 Take a 6 cm diameter petri dish, cover the bottom of the dish with a layer of filter paper, and add a proper amount of tap water to moisturize. The cabbage leaves of suitable size (about 3 cm in diameter) and 15 to 30 aphids were cut from the cabbage plants of the peach aphid, and the aphids on the front of the winged mites and leaves were removed. After investigating the base, the leaves were placed upside down. In the dish, spray with a hand-held Airbrush sprayer at a pressure of 10 psi (about 0.7 kg/cm 2 ), a spray volume of 0.5 mL, three replicates per treatment, and placed in a standard observation chamber after treatment, 48 hours later. Investigate the number of survivors, calculate mortality and grade.
按照以上方法， 部分测试化合物与已知化合物 Kd (WO9740009中的 11-63号化合物）、 KC2 ( WO9740009 中的 11-15 号化合物）、 KC3 ( JP2005008628 中的 1 号化合物）、 KC4 (WO2007100160中的 1号化合物） 禾 B KC5 (CN101875633中的 5号化合物） 进行了杀桃蚜 活性的平行测定。 试验结果见表 4。 According to the above method, a part of the test compound and the known compound Kd (compound No. 11-63 in WO9740009), KC 2 (compound No. 11-15 in WO9740009), KC 3 (compound No. 1 in JP2005008628), KC 4 (Compound No. 1 in WO2007100160) Wo B KC 5 (Compound No. 5 in CN101875633) Parallel measurement of the activity of Aquilaria serrata was carried out. The test results are shown in Table 4.
表 4: 丙烯腈化合物与已知化合物杀桃蚜活性平行比较  Table 4: Parallel comparison of acrylonitrile compounds with known compounds
Figure imgf000050_0001
Figure imgf000051_0002
Figure imgf000050_0001
Figure imgf000051_0002
Figure imgf000051_0001
Figure imgf000051_0001
3-115 A B 3-115 A B
3-117 A A  3-117 A A
3-122 A B  3-122 A B
3-123 A B  3-123 A B
3-125 A B  3-125 A B
3-146 A B  3-146 A B
3-157 A B  3-157 A B
3-158 A B  3-158 A B
3-170 A B  3-170 A B
3-176 A B  3-176 A B
Kd C D  Kd C D
KC2 D D KC 2 DD
KC3 B C KC 3 BC
KC4 A D KC 4 AD
KC5 D D KC 5 DD
13.2 杀小菜蛾活性的测定 13.2 Determination of the activity of Plutella xylostella
将甘蓝叶片用打孔器打成直径 2厘米的叶碟， 用 Airbrush喷雾处理， 压力为 10 psi (约合 0.7 kg/cm2), 每叶碟正反面喷雾， 喷液量为 0.5 mL。 阴干后每处理接入 10头 2龄试虫， 每处 理 3次重复。 处理后放入 25°C、 相对湿度 60〜70%观察室内培养， 72小时后调查存活虫数， 计算死亡率并分级。 The cabbage leaves were punched into 2 cm diameter discs with a puncher and sprayed with Airbrush at a pressure of 10 psi (about 0.7 kg/cm 2 ). The spray was sprayed on the front and back of each leaf with a spray volume of 0.5 mL. After the dryness, 10 heads of 2nd intestines were connected to each treatment, and each treatment was repeated 3 times. After the treatment, the cells were cultured at 25 ° C and a relative humidity of 60 to 70%, and the number of viable animals was investigated after 72 hours, and the mortality was calculated and classified.
部分供试的化合物中， 下列化合物在浓度为 600 ppm时对小菜蛾的防治效果较好， 死亡 率在 B 级以上： 1-2、 1-3、 1-4、 1-10、 1-16、 1-17、 1-22、 1-23、 1-25、 1-33、 1-37、 1-38、 Among the compounds tested, the following compounds had better control effects on Plutella xylostella at a concentration of 600 ppm, and the mortality rate was above B: 1-2, 1-3, 1-4, 1-10, 1-16 , 1-17, 1-22, 1-23, 1-25, 1-33, 1-37, 1-38,
1— 44、 1-45、 1-47、 1-48、 1-53、 1-54、 1-58、 1-63、 1-64、 1-86、 1-88、 1-94、 1-99、 1-101、 1-107、 1-114、 1-120、 1-122、 1-125、 1-127、 1-135、 1-139、 1-151、 1-156、 1-160、 2-1、 2-3、1-44, 1-45, 1-47, 1-48, 1-53, 1-54, 1-58, 1-63, 1-64, 1-86, 1-88, 1-94, 1- 99, 1-101, 1-107, 1-114, 1-120, 1-122, 1-125, 1-127, 1-135, 1-139, 1-151, 1-156, 1-160, 2-1, 2-3,
2- 5、 2-7、 2-10、 2-11、 2-13、 2-17、 2-19、 2-21、 2-22、 2-24、 2-25、 2-26、 2-27、 2-32、 2-33、 2-35、 2-37、 2-43、 2-45、 2-47、 2-49、 2-55、 2-56、 2-58、 2-61、 2-66、 2-68、 2-71、 2-73、 2-79、 2-80、 2-104、 2-110、 2-116、 2-124、 2-141、 2-142、 2-143、 2-152、 2-154、 2-156、 2-160、2- 5, 2-7, 2-10, 2-11, 2-13, 2-17, 2-19, 2-21, 2-22, 2-24, 2-25, 2-26, 2- 27, 2-32, 2-33, 2-35, 2-37, 2-43, 2-45, 2-47, 2-49, 2-55, 2-56, 2-58, 2-61, 2-66, 2-68, 2-71, 2-73, 2-79, 2-80, 2-104, 2-110, 2-116, 2-124, 2-141, 2-142, 2- 143, 2-152, 2-154, 2-156, 2-160,
2- 161、 2-166、 2-168、 2-172、 2-173、 2-174、 2-179、 2-181、 2-247、 2-248、 2-249、 2-250、 2-255、 2-260、 2-261、 2-266、 2-268、 2-271、 2-273、 2-279、 2-280、 2-285、 2-292、 2-294、2- 161, 2-166, 2-168, 2-172, 2-173, 2-174, 2-179, 2-181, 2-247, 2-248, 2-249, 2-250, 2- 255, 2-260, 2-261, 2-266, 2-268, 2-271, 2-273, 2-279, 2-280, 2-285, 2-292, 2-294,
3- 2、 3-4、 3-5、 3-6、 3-7、 3-8、 3-9、 3-17、 3-26、 3-34、 3-44、 3-45、 3-47、 3-52、 3-54、 3-57、 3-59、 3-65、 3-67、 3-79、 3-86、 3-98、 3-103、 3-105、 3-144、 3-150、 3-152、 3-156、 3-157、 3-158、 3-168、 3-170、 3-175、 3-176、 3-177。 3- 2, 3-4, 3-5, 3-6, 3-7, 3-8, 3-9, 3-17, 3-26, 3-34, 3-44, 3-45, 3- 47, 3-52, 3-54, 3-57, 3-59, 3-65, 3-67, 3-79, 3-86, 3-98, 3-103, 3-105, 3-144, 3-150, 3-152, 3-156, 3-157, 3-158, 3-168, 3-170, 3-175, 3-176, 3-177.
部分供试的化合物中， 下列化合物在浓度为 100 ppm时对小菜蛾的防治效果较好， 死亡 率在 B级以上： 1-58、 1-63、 2-3、 2-19、 2-68、 2-172、 2-173、 2-285、 3-2、 3-4、 3-5、 3-6、 Among the compounds tested, the following compounds had better control effects on Plutella xylostella at a concentration of 100 ppm, and the mortality rate was above Grade B: 1-58, 1-63, 2-3, 2-19, 2-68 , 2-172, 2-173, 2-285, 3-2, 3-4, 3-5, 3-6,
3-7、 3-8、 3-9、 3-17、 3-44、 3-45、 3-47、 3-52、 3-54、 3-57、 3-59、 3-65、 3-67、 3-144、 3-150、 3-152、 3-156、 3-157、 3-158、 3-168、 3-170、 3-175、 3-176、 3-177。 3-7, 3-8, 3-9, 3-17, 3-44, 3-45, 3-47, 3-52, 3-54, 3-57, 3-59, 3-65, 3- 67, 3-144, 3-150, 3-152, 3-156, 3-157, 3-158, 3-168, 3-170, 3-175, 3-176, 3-177.
13.3 杀粘虫活性的测定  13.3 Determination of the activity of killer
将玉米叶片剪成长 2厘米的叶段， 用 Airbrush喷雾处理， 压力为 10 psi (约合 0.7 kg/cm2), 每叶段正反面喷雾， 喷液量为 0.5 mL。 阴干后每处理接入 10头 2龄试虫， 每处理 3次重复。 处理后放入 25°C、相对湿度 60〜70%观察室内培养， 72小时后调查存活虫数， 计算死亡率并 分级。 The corn leaves were cut into 2 cm sections and sprayed with Airbrush at a pressure of 10 psi (about 0.7 kg/cm 2 ). The spray was sprayed on the front and back of each leaf section with a spray volume of 0.5 mL. After the dryness, 10 heads of 2nd intestines were connected to each treatment, and each treatment was repeated 3 times. After the treatment, the cells were cultured at 25 ° C and a relative humidity of 60 to 70%, and the number of viable animals was investigated after 72 hours, and the mortality was calculated and classified.
部分供试的化合物中， 下列化合物在浓度为 600 ppm时对粘虫的防治效果较好， 死亡率 在 B级以上： 1-2、 1-3、 1-4、 1-5、 1-16、 1-22、 1-23、 1-25、 1-37、 1-38、 1-44、 1-45、 1-47、 Among the compounds tested, the following compounds had better control effect against armyworms at a concentration of 600 ppm, and the mortality rate was above grade B: 1-2, 1-3, 1-4, 1-5, 1-16 , 1-22, 1-23, 1-25, 1-37, 1-38, 1-44, 1-45, 1-47,
1- 48、 1-53、 1-58、 1-63、 1-64、 1-86、 1-88、 1-94、 1-96、 1-99、 1-101、 1-107、 1-114、 1-120、 1-122、 1-151、 1-156、 2-1、 2-3、 2-5、 2-7、 2-11、 2-13、 2-17、 2-19、 2-21、 2-24、 2-25、 2-26、1-48, 1-53, 1-58, 1-63, 1-64, 1-86, 1-88, 1-94, 1-96, 1-99, 1-101, 1-107, 1- 114, 1-120, 1-122, 1-151, 1-156, 2-1, 2-3, 2-5, 2-7, 2-11, 2-13, 2-17, 2-19, 2-21, 2-24, 2-25, 2-26,
2- 27、 2-32、 2-33、 2-35、 2-37、 2-43、 2-45、 2-47、 2-48、 2-58、 2-61、 2-66、 2-71、 2-73、 2-79、 2-80、 2-104、 2-112、 2-115、 2-122、 2-135、 2-138、 2-141、 2-142、 2-143、 2-144、 2-156、 2-160、 2-161、 2-166、 2-168、 2-172、 2-173、 2-174、 2-179、 2-181、 2-186、 2-190、 2-192、2- 27, 2-32, 2-33, 2-35, 2-37, 2-43, 2-45, 2-47, 2-48, 2-58, 2-61, 2-66, 2- 71, 2-73, 2-79, 2-80, 2-104, 2-112, 2-115, 2-122, 2-135, 2-138, 2-141, 2-142, 2-143, 2-144, 2-156, 2-160, 2-161, 2-166, 2-168, 2-172, 2-173, 2-174, 2-179, 2-181, 2-186, 2- 190, 2-192,
2- 198、 2-199、 2-203、 2-247、 2-248、 2-249、 2-250、 2-255、 2-260、 2-261、 2-266、 2-268、 2-271、 2-273、 2-279、 2-280、 2-283、 2-285、 2-292、 2-294、 3-2、 3-3、 3-4、 3-5、 3-6、 3-7、2- 198, 2-199, 2-203, 2-247, 2-248, 2-249, 2-250, 2-255, 2-260, 2-261, 2-266, 2-268, 2- 271, 2-273, 2-279, 2-280, 2-283, 2-285, 2-292, 2-294, 3-2, 3-3, 3-4, 3-5, 3-6, 3-7,
3- 8、 3-22、 3-15、 3-17、 3-26、 3-28、 3-34、 3-35、 3-44、 3-45、 3-47、 3-52、 3-54、 3-57、 3-59、 3-65、 3-67、 3-79、 3-86、 3-98、 3-103、 3-105、 3-115、 3-117、 3-123、 3-125、 3-170、 3-175。 3- 8, 3-22, 3-15, 3-17, 3-26, 3-28, 3-34, 3-35, 3-44, 3-45, 3-47, 3-52, 3- 54, 3-57, 3-59, 3-65, 3-67, 3-79, 3-86, 3-98, 3-103, 3-105, 3-115, 3-117, 3-123, 3-125, 3-170, 3-175.
部分供试的化合物中， 下列化合物在浓度为 100 ppm时对粘虫的防治效果较好， 死亡率 在 B级以上： 1-37、 1-38、 1-47、 1-48、 1-53、 1-63、 1-64、 1-151、 2-48、 2-173、 2-174、 2-247、 3-2、 3-3、 3-4、 3-5、 3-6、 3-7、 3-8、 3-22、 3-15、 3-17、 3-26、 3-28、 3-34、 3-35、 3-44、 3-45、 3-47、 3-52、 3-54、 3-57、 3-59、 3-65、 3-67、 3-79、 3-98、 3-115、 3-117、 3-123、 3-125、 3-170、 3-175。  Among the compounds tested, the following compounds had better control effect against armyworms at a concentration of 100 ppm, and the mortality rate was above grade B: 1-37, 1-38, 1-47, 1-48, 1-53 , 1-63, 1-64, 1-151, 2-48, 2-173, 2-174, 2-247, 3-2, 3-3, 3-4, 3-5, 3-6, 3 -7, 3-8, 3-22, 3-15, 3-17, 3-26, 3-28, 3-34, 3-35, 3-44, 3-45, 3-47, 3-52 , 3-54, 3-57, 3-59, 3-65, 3-67, 3-79, 3-98, 3-115, 3-117, 3-123, 3-125, 3-170, 3 -175.

Claims

1、 一种丙烯腈类化合物， 如通式 I所示：
Figure imgf000054_0001
1. An acrylonitrile compound, as shown in Formula I:
Figure imgf000054_0001
I  I
式中：  In the formula:
R选自 CrC6烷基、 CrC6卤代烷基、 C3-C8环烷基或 C C6烷氧基或苯基， 苯环上的氢还 可进一步被如下取代基取代： 卤素、 氰基、 硝基、 甲基或卤代甲基； R is selected from C r C 6 alkyl, C r C 6 haloalkyl, C 3 -C 8 cycloalkyl or CC 6 alkoxy or phenyl, and the hydrogen on the phenyl ring may be further substituted with the following substituent: halogen , cyano, nitro, methyl or halomethyl;
A选自如下基团：  A is selected from the following groups:
Figure imgf000054_0002
1选自氯、 溴或碘；
Figure imgf000054_0002
1 is selected from chlorine, bromine or iodine;
X2选自氢、 卤素、 氰基或甲基; X 2 is selected from the group consisting of hydrogen, halogen, cyano or methyl;
X3选自氯、 三氟甲基或硝基： X 3 is selected from the group consisting of chlorine, trifluoromethyl or nitro:
Q选自如下基  Q is selected from the following bases
Figure imgf000054_0003
Figure imgf000054_0003
选自 H、 卤素、 甲基或三氟甲基；  Selected from H, halogen, methyl or trifluoromethyl;
R2选自 H或卤素； R 2 is selected from H or halogen;
或其立体异构体。  Or a stereoisomer thereof.
2、 按照权利要求 1所述的化合物， 其特征在于， 通式 I中：  2. A compound according to claim 1 wherein, in formula I:
R选自 CrC6烷基、 d-C6卤代垸基、 C3-C8环垸基或 CrC6垸氧基或苯基: R is selected from C r C 6 alkyl, dC 6 halogenated fluorenyl, C 3 -C 8 cyclodecyl or C r C 6 decyloxy or phenyl:
A选自如下基团：  A is selected from the following groups:
Figure imgf000054_0004
Figure imgf000054_0004
A, A A, 选自氯或溴； A, AA, Selected from chlorine or bromine;
x2选自氢、 卤素或甲基; x 2 is selected from the group consisting of hydrogen, halogen or methyl;
¾选自氯或三氟甲基；  3⁄4 is selected from chlorine or trifluoromethyl;
Q选自如下基  Q is selected from the following bases
Figure imgf000055_0001
Figure imgf000055_0001
选自 H或卤素；  Selected from H or halogen;
R2选自 H或卤素； R 2 is selected from H or halogen;
或其立体异构体。  Or a stereoisomer thereof.
3、 按照权利要求 2所述的化合物， 其特征在于， 通式 I中:  3. A compound according to claim 2, characterized in that, in the formula I:
R选自 C3-C6烷基、 C3-C6卤代烷基或 CrC4烷氧基； R is selected from C 3 -C 6 alkyl, C 3 -C 6 haloalkyl or C r C 4 alkoxy;
A选自如下基团：  A is selected from the following groups:
Figure imgf000055_0002
1选自氯；
Figure imgf000055_0002
1 is selected from chlorine;
X2选自氢； X 2 is selected from hydrogen;
X3选自三氟甲基; X 3 is selected from trifluoromethyl;
Q选自如下基  Q is selected from the following bases
Figure imgf000055_0003
Figure imgf000055_0003
选自 H、 氟或氯；  Selected from H, fluorine or chlorine;
R2选自 H、 氟或氯； R 2 is selected from H, fluorine or chlorine;
或其立体异构体。  Or a stereoisomer thereof.
4、 一种按照权利要求 1所述的通式 I化合物控制害虫的用途。  4. Use of a compound of formula I according to claim 1 for controlling pests.
5、 一种杀虫组合物， 含有如权利要求 1所述的通式 I所示化合物为活性组分和农业、 林 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%。  5. A pesticidal composition comprising a compound of the formula I according to claim 1 as an active ingredient and an agricultural, forest or hygienic acceptable carrier, the weight percent of active ingredient in the composition It is 1-99%.
6、一种控制害虫的方法，其特征在于：将权利要求 5所述的组合物以每公顷 10克到 1000 的有效剂量施于需要控制的害虫或其生长的介质上。  A method of controlling pests, characterized in that the composition of claim 5 is applied to a pest to be controlled or a medium for growth thereof at an effective dose of from 10 g to 1000 per hectare.
PCT/CN2013/087479 2012-11-23 2013-11-20 Acrylonitrile compounds and uses thereof WO2014079354A1 (en)

Applications Claiming Priority (6)

Application Number Priority Date Filing Date Title
CN201210484457.5A CN103833668B (en) 2012-11-23 2012-11-23 O-trifluoromethyl phenylpropen nitrile compounds and application thereof
CN201210484570.3A CN103833744B (en) 2012-11-23 2012-11-23 1 ethyl pyrazolyl acrylonitrile compound and application thereof
CN201210484570.3 2012-11-23
CN201210484280.9A CN103833670B (en) 2012-11-23 2012-11-23 2-chlorine thiazolyl acrylonitrile compounds and application thereof
CN201210484280.9 2012-11-23
CN201210484457.5 2012-11-23

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Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPH11124306A (en) * 1997-10-22 1999-05-11 Nissan Chem Ind Ltd Insecticidal, acaricidal and fungicidal composition
CN1216530A (en) * 1996-04-25 1999-05-12 日产化学工业株式会社 Ethylene derivatives and pest controlling agents
WO2007100160A1 (en) * 2006-03-03 2007-09-07 Nissan Chemical Industries, Ltd. Acrylonitrile compounds
WO2011144593A1 (en) * 2010-05-18 2011-11-24 Basf Se Pesticidal mixtures comprising insecticides and pyraclostrobin

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN1216530A (en) * 1996-04-25 1999-05-12 日产化学工业株式会社 Ethylene derivatives and pest controlling agents
JPH11124306A (en) * 1997-10-22 1999-05-11 Nissan Chem Ind Ltd Insecticidal, acaricidal and fungicidal composition
WO2007100160A1 (en) * 2006-03-03 2007-09-07 Nissan Chemical Industries, Ltd. Acrylonitrile compounds
WO2011144593A1 (en) * 2010-05-18 2011-11-24 Basf Se Pesticidal mixtures comprising insecticides and pyraclostrobin

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