WO2020156298A1 - Application of malononitrile compound as bactericide - Google Patents

Application of malononitrile compound as bactericide Download PDF

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WO2020156298A1
WO2020156298A1 PCT/CN2020/073096 CN2020073096W WO2020156298A1 WO 2020156298 A1 WO2020156298 A1 WO 2020156298A1 CN 2020073096 W CN2020073096 W CN 2020073096W WO 2020156298 A1 WO2020156298 A1 WO 2020156298A1
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acid
general formula
substituent
consistent
turn
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PCT/CN2020/073096
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张立新
张静
张力群
康卓
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沈阳化工大学
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    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
    • A01N37/00—Biocides, pest repellants or attractants, or plant growth regulators containing organic compounds containing a carbon atom having three bonds to hetero atoms with at the most two bonds to halogen, e.g. carboxylic acids
    • A01N37/44—Biocides, pest repellants or attractants, or plant growth regulators containing organic compounds containing a carbon atom having three bonds to hetero atoms with at the most two bonds to halogen, e.g. carboxylic acids containing at least one carboxylic group or a thio analogue, or a derivative thereof, and a nitrogen atom attached to the same carbon skeleton by a single or double bond, this nitrogen atom not being a member of a derivative or of a thio analogue of a carboxylic group, e.g. amino-carboxylic acids
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
    • A01N43/00—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds
    • A01N43/02—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with one or more oxygen or sulfur atoms as the only ring hetero atoms
    • A01N43/04—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with one or more oxygen or sulfur atoms as the only ring hetero atoms with one hetero atom
    • A01N43/06—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with one or more oxygen or sulfur atoms as the only ring hetero atoms with one hetero atom five-membered rings
    • A01N43/08—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with one or more oxygen or sulfur atoms as the only ring hetero atoms with one hetero atom five-membered rings with oxygen as the ring hetero atom
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
    • A01N43/00—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds
    • A01N43/02—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with one or more oxygen or sulfur atoms as the only ring hetero atoms
    • A01N43/04—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with one or more oxygen or sulfur atoms as the only ring hetero atoms with one hetero atom
    • A01N43/06—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with one or more oxygen or sulfur atoms as the only ring hetero atoms with one hetero atom five-membered rings
    • A01N43/10—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with one or more oxygen or sulfur atoms as the only ring hetero atoms with one hetero atom five-membered rings with sulfur as the ring hetero atom
    • 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
    • A01N43/34—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with one nitrogen atom as the only ring hetero atom
    • A01N43/40—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with one nitrogen atom as the only ring hetero atom six-membered rings
    • 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
    • A01N43/64—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with three nitrogen atoms as the only ring hetero atoms
    • A01N43/647—Triazoles; Hydrogenated triazoles
    • A01N43/653—1,2,4-Triazoles; Hydrogenated 1,2,4-triazoles
    • 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
    • A01N53/00—Biocides, pest repellants or attractants, or plant growth regulators containing cyclopropane carboxylic acids or derivatives thereof
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C253/00—Preparation of carboxylic acid nitriles
    • C07C253/30—Preparation of carboxylic acid nitriles by reactions not involving the formation of cyano groups
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C255/00—Carboxylic acid nitriles
    • C07C255/01—Carboxylic acid nitriles having cyano groups bound to acyclic carbon atoms
    • C07C255/30—Carboxylic acid nitriles having cyano groups bound to acyclic carbon atoms containing cyano groups and singly-bound nitrogen atoms, not being further bound to other hetero atoms, bound to the same unsaturated acyclic carbon skeleton
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D271/00—Heterocyclic compounds containing five-membered rings having two nitrogen atoms and one oxygen atom as the only ring hetero atoms
    • C07D271/02—Heterocyclic compounds containing five-membered rings having two nitrogen atoms and one oxygen atom as the only ring hetero atoms not condensed with other rings
    • C07D271/10—1,3,4-Oxadiazoles; Hydrogenated 1,3,4-oxadiazoles
    • 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
    • C07D277/28—Radicals substituted by nitrogen atoms

Definitions

  • the invention belongs to the field of agricultural bactericides, and specifically relates to the application of a malononitrile compound as a bactericide.
  • Bacterial diseases have become the second most common disease in China’s agricultural production after fungal diseases. According to incomplete statistics, the area of bacterial diseases currently occurring in China is 120 million mu, and the market capacity of bacterial disease control exceeds 20 100 million yuan.
  • agents for the prevention and control of bacterial diseases mainly include relatively large amounts of copper preparations (including organic or inorganic copper preparations) and antibiotic products; among them, copper preparations have low control effects and a large amount of heavy metals are sprayed into the environment. Pollution of soil, water and food has caused environmental and food safety concerns; on the other hand, the massive use of antibiotics may cause human pathogens to become resistant to medical antibiotics.
  • the purpose of the present invention is to provide a malononitrile compound represented by general formula I as a bactericide in the fields of agriculture, forestry or health.
  • n is selected from 0, 1, 2 or 3;
  • W is selected from one of the groups represented by W 1 -W 10 :
  • Y 1 , Y 2 , Y 3 , and Y 4 are each independently selected from hydrogen, halogen, cyano, C 1 -C 6 alkyl, halo C 1 -C 6 alkyl, C 1 -C 6 alkoxy, Halogenated C 1 -C 6 alkoxy, C 1 -C 6 alkylthio or halogenated C 1 -C 6 alkylthio;
  • Z 1 , Z 2 , Z 3 , Z 4 , Z 5 , Z 6 , and Z 7 are each independently selected from hydrogen, halogen or C 1 -C 6 alkyl;
  • R 1 is selected from hydrogen, hydroxyl, mercapto, amino, cyano, C 1 -C 6 alkyl, C 1 -C 6 alkoxy, halogenated C 1 -C 6 alkoxy, C 1 -C 6 alkyl sulfide Group, halogenated C 1 -C 6 alkylthio, C 1 -C 6 alkylamino or C 1 -C 6 dialkylamino;
  • R 2 is selected from hydrogen, C 1 -C 6 alkyl, halogenated C 1 -C 6 alkyl, cyano C 1 -C 6 alkyl, C 1 -C 6 alkylcarbonyl, C 3 -C 6 cycloalkane Carbonyl or C 1 -C 6 alkoxycarbonyl;
  • the preferred compound is:
  • n is selected from 0 or 1;
  • W is selected from one of the groups represented by W 1 -W 10 :
  • Y 1 , Y 2 , Y 3 , and Y 4 are each independently selected from hydrogen, halogen, cyano, C 1 -C 4 alkyl, halo C 1 -C 4 alkyl, C 1 -C 4 alkoxy, Halogenated C 1 -C 4 alkoxy, C 1 -C 4 alkylthio or halogenated C 1 -C 4 alkylthio;
  • Z 1 , Z 2 , Z 3 , Z 4 , Z 5 , Z 6 , and Z 7 are each independently selected from hydrogen, halogen or C 1 -C 4 alkyl;
  • R 1 is selected from hydrogen, hydroxyl, mercapto, amino, cyano, C 1 -C 4 alkyl, C 1 -C 4 alkoxy, halogenated C 1 -C 4 alkoxy, C 1 -C 4 alkyl sulfide Group, halogenated C 1 -C 4 alkylthio, C 1 -C 4 alkylamino or C 1 -C 4 dialkylamino;
  • R 2 is selected from hydrogen, C 1 -C 4 alkyl, halogenated C 1 -C 4 alkyl, cyano C 1 -C 4 alkyl, C 1 -C 4 alkylcarbonyl, C 3 -C 6 cycloalkane Carbonyl or C 1 -C 4 alkoxycarbonyl;
  • n is selected from 0 or 1;
  • W is selected from one of the groups represented by W 1 -W 10 :
  • X 1 , X 2 , X 3 , X 4 , and X 5 are each independently selected from hydrogen, fluorine, chlorine, bromine, cyano, nitro, hydroxyl, mercapto, amino, carboxy, methyl, ethyl, n-propyl , Isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, monochloromethyl, dichloromethyl, trichloromethyl, monobromomethyl, dibromomethyl, tribromomethyl , Monofluoromethyl, difluoromethyl, trifluoromethyl, 2,2,2-trifluoroethyl, heptafluoroisopropyl, methoxy, ethoxy, n-propoxy, isopropoxy , Difluoromethoxy, trifluoromethoxy, methylthio, ethylthio, trifluoromethylthio, 2,2,2-trifluoro
  • Y 1 , Y 2 , Y 3 , and Y 4 are each independently selected from hydrogen, fluorine, chlorine, bromine, cyano, methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec Butyl, tert-butyl, monochloromethyl, dichloromethyl, trichloromethyl, monobromomethyl, dibromomethyl, tribromomethyl, monofluoromethyl, difluoromethyl, trifluoromethyl Group, 2,2,2-trifluoroethyl, heptafluoroisopropyl, methoxy, ethoxy, n-propoxy, isopropoxy, difluoromethoxy, trifluoromethoxy, methyl Thio, ethylthio, trifluoromethylthio or 2,2,2-trifluoroethylthio;
  • Z 1 , Z 2 , Z 3 , Z 4 , Z 5 , Z 6 , and Z 7 are each independently selected from hydrogen, fluorine, chlorine, bromine, methyl, ethyl, n-propyl, isopropyl, n-butyl , Isobutyl, sec-butyl or tert-butyl;
  • R 1 is selected from hydrogen, hydroxyl, mercapto, amino, cyano, methyl, ethyl, n-propyl, n-butyl, methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy Group, methylthio, ethylthio, n-propylthio, n-butylthio, methylamino, ethylamino, n-propylamino or n-butylamino;
  • R 2 is selected from hydrogen, methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, cyanomethyl, 2,2,2-trifluoroethyl , Acetyl, n-propionyl, cyclopropylformyl, methoxycarbonyl, ethoxycarbonyl, n-propoxycarbonyl or n-butoxycarbonyl;
  • n is selected from 0 or 1;
  • W is selected from one of the groups represented by W 1 -W 10 :
  • Y 1 , Y 2 , Y 3 , and Y 4 are selected from hydrogen;
  • Z 1 , Z 2 , Z 3 , Z 4 , Z 5 , Z 6 , and Z 7 are selected from hydrogen;
  • R 1 is selected from hydrogen, amino, methyl, methoxy, ethoxy, methylthio, ethylthio, methylamino or ethylamino;
  • R 2 is selected from hydrogen, methyl, ethyl, 2,2,2-trifluoroethyl, cyanomethyl, acetyl, n-propionyl, cyclopropylformyl, methoxycarbonyl or ethoxycarbonyl;
  • Halogen refers to fluorine, chlorine, bromine or iodine.
  • Alkyl straight or branched chain alkyl, such as methyl, ethyl, n-propyl, isopropyl or different butyl, pentyl or hexyl isomers.
  • Halogenated alkyl groups straight or branched chain alkyl groups.
  • the hydrogen atoms on these alkyl groups can be partially or completely replaced by halogens, such as monochloromethyl, dichloromethyl, trichloromethyl, monobromomethyl, and dichloromethyl.
  • Cyanoalkyl straight or branched chain alkyl groups, the hydrogen atoms on these alkyl groups can be partially or completely replaced by cyano groups, such as cyanomethyl (CNCH 2 -), cyanoethyl (CNCH 2 CH 2- ), CNCH 2 CH 2 CH 2 -, CNCH 2 CH 2 CH 2 CH 2 -etc.
  • Alkoxy straight or branched chain alkyl, connected to the structure via oxygen atom bond, such as methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy, tert-butoxy, etc. .
  • Halogenated alkoxy groups straight or branched chain alkoxy groups, the hydrogen atoms on these alkoxy groups can be partially or completely replaced by halogens, such as chloromethoxy, dichloromethoxy, trichloromethoxy, fluorine Methoxy, difluoromethoxy, trifluoromethoxy, chlorofluoromethoxy, 2,2,2-trifluoroethoxy, etc.
  • halogens such as chloromethoxy, dichloromethoxy, trichloromethoxy, fluorine Methoxy, difluoromethoxy, trifluoromethoxy, chlorofluoromethoxy, 2,2,2-trifluoroethoxy, etc.
  • Alkylthio straight or branched chain alkyl, connected to the structure via a sulfur atom bond, such as methylthio, ethylthio and the like.
  • Halogenated alkylthio linear or branched alkylthio, the hydrogen atoms on these alkylthio groups can be partially or completely replaced by halogen, such as difluoromethylthio, trifluoromethylthio, 2,2,2- Trifluoroethylthio and so on.
  • Alkylamino straight or branched chain alkyl, connected to the structure via a nitrogen atom bond, such as methylamino, ethylamino, n-propylamino, isopropylamino or isomeric butylamine.
  • Dialkylamino Two identical or different linear or branched alkyl groups are connected to the structure via a nitrogen atom bond, such as N,N-dimethylamino, N-methyl-N-ethylamino, etc.
  • Alkylcarbonyl The alkyl group is connected to the structure via the carbonyl group, such as acetyl (CH3CO-), n-propionyl (CH3CH2CO-) and so on.
  • Cycloalkylcarbonyl Cycloalkyl is attached to the structure via a carbonyl group, such as cyclopropylformyl.
  • Alkoxycarbonyl alkyl-O-CO-, such as methoxycarbonyl (CH 3 OCO-), ethoxycarbonyl (CH 3 CH 2 OCO-), n-propoxycarbonyl (CH 3 CH 2 CH 2 OCO-), n-butoxycarbonyl (CH 3 CH 2 CH 2 CH 2 OCO-), etc.
  • Table 22 In the general formula IW 1 -1, when R 1 ⁇ OCH 2 CH 3 and R 2 ⁇ CH 3 , the substituent R is consistent with Table 1, which represents the compound number 22.1-22.360, corresponding to 1.1- in Table 1 in turn 1.360.
  • Table 32 In the general formula IW 1 -1, when R 1 ⁇ OCH 3 and R 2 ⁇ CH 2 CH 3 , the substituent R is consistent with Table 1, and the representative compound number is 32.1-32.360, corresponding to 1.1- in Table 1 in turn 1.360.
  • Table 43 In the general formula IW 1 -1, when R 1 ⁇ OCH 3 and R 2 ⁇ CH 2 CN, the substituent R is consistent with Table 1, and the representative compound number is 43.1-43.360, corresponding to 1.1-1.360 in Table 1 in turn .
  • Table 120 In the general formula IW 1 -0, when R 1 ⁇ OCH 3 and R 2 ⁇ CH 3 , the substituent R is consistent with Table 1, and the representative compound number is 120.1-120.360, corresponding to 1.1-1.360 of Table 1 in turn.
  • Table 142 In the general formula IW 1 -0, when R 1 ⁇ OCH 3 and R 2 ⁇ CH 2 CN, the substituent R is consistent with Table 1, and the representative compound number is 142.1-142.360, corresponding to 1.1-1.360 in Table 1 in turn .
  • the compound of general formula I of the present invention can be prepared according to the following method (each group in the formula is defined as above unless otherwise specified):
  • Method 1 When R 1 is hydrogen or C 1 -C 6 alkyl, the compound of general formula I can be prepared by the following method (where Alkoxyl represents C 1 -C 6 alkoxy, such as methoxy, ethoxy Wait):
  • the compound of general formula II-1 and the compound of general formula III-1 are reacted in a suitable solvent at a temperature from -10°C to the boiling point of the solvent for 0.5-48 hours to obtain a compound of general formula I-1; the reaction can be carried out in the presence of a base .
  • suitable solvents can be the same or different, and can be alcohols (e.g., methanol, ethanol, etc.), aromatic hydrocarbons (e.g., benzene, toluene, xylene, etc.), ketones (e.g., acetone, methyl ethyl ketone, methyl Isobutyl ketone, etc.), halogenated hydrocarbons (such as chloroform, dichloromethane, etc.), esters (such as methyl acetate, ethyl acetate, etc.), ethers (such as tetrahydrofuran, dioxane, diethyl ether) , 1,2-dimethoxyethane, etc.), polar solvents (such as water, acetonitrile, dioxane, N,N-dimethylformamide, N-methylpyrrolidone, dimethylene Sulfone, etc.) or a mixed solvent of the above solvents.
  • alcohols
  • the bases can be the same or different, and can be organic bases such as trimethylamine, triethylamine, pyridine, DBU, 4-dimethylaminopyridine (eg, trimethylamine, triethylamine, pyridine, DBU, 4-dimethylaminopyridine, etc.) , Alkali metal hydrides (such as sodium hydride, potassium hydride, etc.), alkali metal hydroxides (such as sodium hydroxide, potassium hydroxide, etc.), alkaline earth metal hydroxides (such as calcium hydroxide, etc.), alkali Metal carbonates (such as sodium carbonate, potassium carbonate, etc.), alkali metal bicarbonates (such as sodium bicarbonate, etc.), metal alkoxides (such as sodium methoxide, sodium ethoxide, potassium ethoxide, potassium tert-butoxide, tertiary Sodium butoxide, etc.).
  • Alkali metal hydrides such as sodium hydride, potassium hydr
  • Method 2 When R 1 is C 1 -C 6 alkylthio or halogenated C 1 -C 6 alkylthio, the compound of general formula I can be prepared according to the following method (where A represents C 1 -C 6 alkyl Or halogenated C 1 -C 6 alkyl):
  • the method of preparing the compound of general formula I-4 from the compound of general formula I-3 is the same as the method of preparing the compound of general formula I-2 from the compound of general formula I-1.
  • suitable solvents can be the same or different, and can be alcohols (e.g., methanol, ethanol, etc.), aromatic hydrocarbons (e.g., benzene, toluene, xylene, etc.), ketones (e.g., acetone, methyl ethyl ketone, methyl Isobutyl ketone, etc.), halogenated hydrocarbons (such as chloroform, dichloromethane, etc.), esters (such as methyl acetate, ethyl acetate, etc.), ethers (such as tetrahydrofuran, dioxane, diethyl ether) , 1,2-dimethoxyethane, etc.), polar solvents (such as water, acetonitrile, dioxane, N,N-dimethylformamide, N-methylpyrrolidone, dimethylene Sulfone, etc.) or a mixed solvent of the above solvents.
  • alcohols
  • the bases can be the same or different, and can be organic bases such as trimethylamine, triethylamine, pyridine, DBU, 4-dimethylaminopyridine (eg, trimethylamine, triethylamine, pyridine, DBU, 4-dimethylaminopyridine, etc.) , Alkali metal hydrides (such as sodium hydride, potassium hydride, etc.), alkali metal hydroxides (such as sodium hydroxide, potassium hydroxide, etc.), alkaline earth metal hydroxides (such as calcium hydroxide, etc.), alkali Metal carbonates (such as sodium carbonate, potassium carbonate, etc.), alkali metal bicarbonates (such as sodium bicarbonate, etc.), metal alkoxides (such as sodium methoxide, sodium ethoxide, potassium ethoxide, potassium tert-butoxide, tertiary Sodium butoxide, etc.).
  • Alkali metal hydrides such as sodium hydride, potassium hydr
  • the nucleophile is sodium hydroxide, potassium hydroxide, lithium hydroxide, sodium hydrosulfide, sodium amide, ammonia, C 1 -C 6 alkyl ammonia (such as methylamine, ethylamine, etc.) or its hydrochloric acid Salt (such as methylamine hydrochloride, ethylamine hydrochloride, etc.).
  • Suitable bases are preferably trimethylamine, triethylamine, pyridine, and carbonic acid. Potassium, sodium carbonate, potassium bicarbonate, sodium bicarbonate, etc.
  • suitable solvents can be the same or different, and can be alcohols (e.g., methanol, ethanol, etc.), aromatic hydrocarbons (e.g., benzene, toluene, xylene, etc.), ketones (e.g., acetone, methyl ethyl ketone, methyl Isobutyl ketone, etc.), halogenated hydrocarbons (such as chloroform, dichloromethane, etc.), esters (such as methyl acetate, ethyl acetate, etc.), ethers (such as tetrahydrofuran, dioxane, diethyl ether) , 1,2-dimethoxyethane, etc.), polar solvents (such as water, acetonitrile, dioxane, N,N-dimethylformamide, N-methylpyrrolidone, dimethylene Sulfone, etc.) or a mixed solvent of the above solvents.
  • alcohols
  • the nucleophile is sodium cyanide, potassium cyanide, alkali metal salts of C 1 -C 6 alkanols (such as sodium methoxide, potassium methoxide, sodium ethoxide, potassium ethoxide, etc.), halogenated C 1 -C 6 Alkali metal salt of alkanol (such as sodium 2,2,2-trifluoroethoxide or potassium 2,2,2-trifluoroethoxide, etc.), C 1 -C 6 dialkyl ammonia (such as N,N-dimethyl Ammonia, N-methyl-N-ethylamine, etc.) or its hydrochloride (such as N,N-dimethylammonium hydrochloride, N-methyl-N-ethylammonium hydrochloride, etc.).
  • C 1 -C 6 alkanols such as sodium methoxide, potassium methoxide, sodium ethoxide, potassium ethoxide, etc.
  • Suitable bases are preferably trimethylamine, triethylamine, pyridine, Potassium carbonate, sodium carbonate, potassium bicarbonate, sodium bicarbonate, etc.
  • suitable solvents can be the same or different, and can be alcohols (e.g., methanol, ethanol, etc.), aromatic hydrocarbons (e.g., benzene, toluene, xylene, etc.), ketones (e.g., acetone, methyl ethyl ketone, methyl Isobutyl ketone, etc.), halogenated hydrocarbons (such as chloroform, dichloromethane, etc.), esters (such as methyl acetate, ethyl acetate, etc.), ethers (such as tetrahydrofuran, dioxane, diethyl ether) , 1,2-dimethoxyethane, etc.), polar solvents (such as water, acetonitrile, dioxane, N,N-dimethylformamide, N-methylpyrrolidone, dimethylene Sulfone, etc.) or a mixed solvent of the above solvents.
  • alcohols
  • the method for preparing compounds of general formula I-8 from compounds of general formula I-7 is the same as the method for preparing compounds of general formula I-2 from compounds of general formula I-1.
  • R 1 is hydrogen or C 1 -C 6 alkyl
  • the compound of general formula II-1 can be prepared by reacting compound of general formula III-2 with compound of general formula I-9.
  • the method for preparing the compound of the general formula I-9 from the compound of the general formula II-1 is the same as the method for preparing the compound of the general formula I-1 from the compound of the general formula II-1.
  • R 1 is not hydrogen or C 1 -C 6 alkyl (where K represents hydroxyl, mercapto, amino, cyano, C 1 -C 6 alkoxy, halogenated C 1 -C 6 alkoxy Group, C 1 -C 6 alkylamino or C 1 -C 6 dialkylamino):
  • the compound of general formula II-2 can be reacted with compound of general formula III-2 to prepare compound of general formula I-10.
  • the method for preparing the compound of the general formula I-10 from the compound of the general formula II-2 is the same as the method for preparing the compound of the general formula I-3 from the compound of the general formula II-2.
  • the compound of general formula I-10 can be prepared by reacting the compound of general formula I-10 with a nucleophile.
  • the method for preparing the compound of the general formula I-11 from the compound of the general formula I-10 is the same as the method for preparing the compound of the general formula I-6 from the compound of the general formula I-4 or preparing the compound of the general formula I-8 from the compound of the general formula I-4.
  • the compound of general formula II-1 can be purchased or according to known methods (for example, US2503524, RSC Advances, 6(29), 24491-24500; 2016, Huaxue Shiji, 35(9), 849-850; 2013, WO2010019637, WO2014139326, WO2004009602 , WO2005117909, WO2010086118).
  • the compound of general formula II-2 can be purchased or according to known methods (e.g. Organic Process Research & Development, 15(3), 556-564; 2011, CN102001977, WO2018089786, Journal of Enzyme Inhibition and Medicinal Chemistry, 28(1), 163-171 ; The method described in 2013).
  • the compound of general formula III-1, compound of general formula III-2 and other raw materials and reagents can be purchased or self-made according to conventional methods.
  • the compound represented by the general formula I of the present invention is used to control plant bacterial diseases, and can be used to prevent and control a variety of plant bacterial diseases, such as fruit spot disease (such as melon fruit spot, etc.), leaf spot disease (such as tomato bacteria) Leaf spot disease, etc.), bacterial wilt (such as tomato bacterial wilt, potato bacterial wilt, etc.), bacterial blight, canker disease (such as citrus canker, kiwi fruit canker, etc.), soft rot (such as soft Chinese cabbage) Rot, etc.), bacterial angular leaf spot (such as cucumber bacterial angular leaf spot, etc.), bacterial leaf streak (such as rice bacterial leaf spot, etc.), leaf blight, bacterial leaf blight (such as rice white leaf Blight, etc.), wildfire and bacterial scab.
  • plant bacterial diseases such as fruit spot disease (such as melon fruit spot, etc.), leaf spot disease (such as tomato bacteria) Leaf spot disease, etc.), bacterial w
  • the compounds represented by the general formula I of the present invention can be prepared separately, which are further described in detail as follows:
  • the raw material 2-(bis(methylthio)methylene)malononitrile can be prepared according to known methods, for example, refer to the method reported in Organic Process Research & Development, 15(3), 556-564; 2011.
  • Example 26 Determination of the control effect on plant bacterial diseases
  • the compound of the present invention has been used for the prevention and control of various plant bacterial diseases.
  • the test procedure is as follows:
  • melon fruit spot disease For melon fruit spot disease, dissolve the test compound with a small amount of N,N dimethylformamide and dilute with water to the required concentration.
  • the pathogenic bacteria cultivated to the stable growth period are mixed with the quantitative compound solution uniformly, the melon seeds that have been germinated are soaked in the mixture of the bacterial solution and the compound for half an hour, and then the seeds are sown in the earthworm soil culture cup and placed in the greenhouse Medium moisturizing culture, usually cultured for two weeks, after the control is fully onset, the control effect investigation will be carried out.
  • the compound is sprayed on the surface of the plant test material, the surface drug solution is air-dried in a cool place, and the pathogenic bacteria liquid cultured to a stable growth stage is sprayed on the surface of the plant test material, and then the plant test material is placed in a greenhouse for moisturizing culture. It is usually cultivated for about ten days, and after the control has fully developed disease, the control effect investigation will be conducted.

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Abstract

Disclosed by the present invention is an application of a malononitrile compound as represented by general formula I as a bactericide. See the description for the definition of each substituent in the formula. The compound represented by general formula I has excellent bactericidal activity and can be used to control various plant bacterial diseases.

Description

一种丙二腈类化合物作为杀细菌剂的应用Application of a kind of malononitrile compound as bactericide 技术领域Technical field
本发明属农用杀细菌剂领域，具体地涉及一种丙二腈类化合物作为杀细菌剂的应用。The invention belongs to the field of agricultural bactericides, and specifically relates to the application of a malononitrile compound as a bactericide.
背景技术Background technique
细菌性病害已成为我国农业生产中仅次于真菌性病害的第二大常发性病害，据不完全统计，我国细菌性病害目前发生面积在1.2亿亩次，细菌性病害防治市场容量超过20亿元。目前农业生产中，防治细菌性病害药剂主要包括用量较大的铜制剂(包括有机或无机铜制剂)和抗生素类产品；其中，铜制剂的防效较低并且大量的重金属喷施到环境中，对土壤、水体和食品形成污染，引发环境及食品的安全担忧；而另一方面，抗生素的大量使用，可能引起人体病原菌对医用抗生素产生抗药性。其它能用于农业细菌治疗的仅有少量品种，实际生产中受到抗性及防效的双重限制，推广面积较小。因此，研发新型、高效、低毒、环境友好型细菌性病害防治药剂是非常必要而迫切的。Bacterial diseases have become the second most common disease in China’s agricultural production after fungal diseases. According to incomplete statistics, the area of bacterial diseases currently occurring in China is 120 million mu, and the market capacity of bacterial disease control exceeds 20 100 million yuan. At present, in agricultural production, agents for the prevention and control of bacterial diseases mainly include relatively large amounts of copper preparations (including organic or inorganic copper preparations) and antibiotic products; among them, copper preparations have low control effects and a large amount of heavy metals are sprayed into the environment. Pollution of soil, water and food has caused environmental and food safety concerns; on the other hand, the massive use of antibiotics may cause human pathogens to become resistant to medical antibiotics. There are only a small number of other varieties that can be used for agricultural bacteria treatment. In actual production, they are restricted by resistance and control effect, and the promotion area is small. Therefore, it is very necessary and urgent to develop new, high-efficiency, low-toxicity, and environmentally-friendly antibacterial agents for bacterial diseases.
现有技术中，如本发明所示的丙二腈类化合物作为杀细菌剂的应用未见报道。In the prior art, the application of malononitrile compounds as shown in the present invention as bactericides has not been reported.
发明内容Summary of the invention
本发明的目的是提供一种如通式I所示的丙二腈类化合物在农业、林业或卫生领域中作为杀细菌剂的应用。The purpose of the present invention is to provide a malononitrile compound represented by general formula I as a bactericide in the fields of agriculture, forestry or health.
本发明的技术方案如下：The technical scheme of the present invention is as follows:
一种丙二腈类化合物作为杀细菌剂的应用，丙二腈类化合物结构如通式I所示：The application of a malononitrile compound as a bactericide, the structure of the malononitrile compound is shown in general formula I:
Figure PCTCN2020073096-appb-000001
Figure PCTCN2020073096-appb-000001
式中：Where:
n选自0、1、2或3；n is selected from 0, 1, 2 or 3;
W选自W 1-W 10所示基团之一： W is selected from one of the groups represented by W 1 -W 10 :
Figure PCTCN2020073096-appb-000002
Figure PCTCN2020073096-appb-000002
X 1、X 2、X 3、X 4、X 5各自独立地选自氢、卤素、氰基、硝基、羟基、巯基、氨基、羧基、C 1-C 6烷基、卤代C 1-C 6烷基、C 1-C 6烷氧基、卤代C 1-C 6烷氧基、C 1-C 6烷硫基、卤代C 1-C 6烷硫基、C 1-C 6烷基氨基、C 1-C 6二烷基氨基、C 1-C 6烷基羰基、C 1-C 6烷氧基羰基、-NHCH＝C(CN) 2或-CH 2NHCH＝C(CN) 2； X 1 , X 2 , X 3 , X 4 , and X 5 are each independently selected from hydrogen, halogen, cyano, nitro, hydroxyl, mercapto, amino, carboxy, C 1 -C 6 alkyl, halogenated C 1- C 6 alkyl, C 1 -C 6 alkoxy, halogenated C 1 -C 6 alkoxy, C 1 -C 6 alkylthio, halogenated C 1 -C 6 alkylthio, C 1 -C 6 Alkylamino, C 1 -C 6 dialkylamino, C 1 -C 6 alkylcarbonyl, C 1 -C 6 alkoxycarbonyl, -NHCH=C(CN) 2 or -CH 2 NHCH=C(CN ) 2 ;
Y 1、Y 2、Y 3、Y 4各自独立地选自氢、卤素、氰基、C 1-C 6烷基、卤代C 1-C 6烷基、C 1-C 6烷氧基、卤代C 1-C 6烷氧基、C 1-C 6烷硫基或卤代C 1-C 6烷硫基； Y 1 , Y 2 , Y 3 , and Y 4 are each independently selected from hydrogen, halogen, cyano, C 1 -C 6 alkyl, halo C 1 -C 6 alkyl, C 1 -C 6 alkoxy, Halogenated C 1 -C 6 alkoxy, C 1 -C 6 alkylthio or halogenated C 1 -C 6 alkylthio;
Z 1、Z 2、Z 3、Z 4、Z 5、Z 6、Z 7各自独立地选自氢、卤素或C 1-C 6烷基； Z 1 , Z 2 , Z 3 , Z 4 , Z 5 , Z 6 , and Z 7 are each independently selected from hydrogen, halogen or C 1 -C 6 alkyl;
R 1选自氢、羟基、巯基、氨基、氰基、C 1-C 6烷基、C 1-C 6烷氧基、卤代C 1-C 6烷氧基、C 1-C 6烷硫基、卤代C 1-C 6烷硫基、C 1-C 6烷基氨基或C 1-C 6二烷基氨基； R 1 is selected from hydrogen, hydroxyl, mercapto, amino, cyano, C 1 -C 6 alkyl, C 1 -C 6 alkoxy, halogenated C 1 -C 6 alkoxy, C 1 -C 6 alkyl sulfide Group, halogenated C 1 -C 6 alkylthio, C 1 -C 6 alkylamino or C 1 -C 6 dialkylamino;
R 2选自氢、C 1-C 6烷基、卤代C 1-C 6烷基、氰基C 1-C 6烷基、C 1-C 6烷基羰基、C 3-C 6环烷基羰基或C 1-C 6烷氧基羰基； R 2 is selected from hydrogen, C 1 -C 6 alkyl, halogenated C 1 -C 6 alkyl, cyano C 1 -C 6 alkyl, C 1 -C 6 alkylcarbonyl, C 3 -C 6 cycloalkane Carbonyl or C 1 -C 6 alkoxycarbonyl;
或通式I化合物的盐。Or the salt of the compound of formula I.
通式I化合物作为杀细菌剂的应用时较优选的化合物为：When the compound of formula I is used as a bactericide, the preferred compound is:
n选自0或1；n is selected from 0 or 1;
W选自W 1-W 10所示基团之一： W is selected from one of the groups represented by W 1 -W 10 :
X 1、X 2、X 3、X 4、X 5各自独立地选自氢、卤素、氰基、硝基、羟基、巯基、氨基、羧基、C 1-C 4烷基、卤代C 1-C 4烷基、C 1-C 4烷氧基、卤代C 1-C 4烷氧基、C 1-C 4烷硫基、卤代C 1-C 4烷硫基、C 1-C 4烷基氨基、C 1-C 4二烷基氨基、C 1-C 4烷基羰基、C 1-C 4烷氧基羰基、-NHCH＝C(CN) 2或-CH 2NHCH＝C(CN) 2； X 1 , X 2 , X 3 , X 4 , and X 5 are each independently selected from hydrogen, halogen, cyano, nitro, hydroxyl, mercapto, amino, carboxy, C 1 -C 4 alkyl, halogenated C 1- C 4 alkyl, C 1 -C 4 alkoxy, halogenated C 1 -C 4 alkoxy, C 1 -C 4 alkylthio, halogenated C 1 -C 4 alkylthio, C 1 -C 4 Alkylamino, C 1 -C 4 dialkylamino, C 1 -C 4 alkylcarbonyl, C 1 -C 4 alkoxycarbonyl, -NHCH=C(CN) 2 or -CH 2 NHCH=C(CN ) 2 ;
Y 1、Y 2、Y 3、Y 4各自独立地选自氢、卤素、氰基、C 1-C 4烷基、卤代C 1-C 4烷基、C 1-C 4烷氧基、卤代C 1-C 4烷氧基、C 1-C 4烷硫基或卤代C 1-C 4烷硫基； Y 1 , Y 2 , Y 3 , and Y 4 are each independently selected from hydrogen, halogen, cyano, C 1 -C 4 alkyl, halo C 1 -C 4 alkyl, C 1 -C 4 alkoxy, Halogenated C 1 -C 4 alkoxy, C 1 -C 4 alkylthio or halogenated C 1 -C 4 alkylthio;
Z 1、Z 2、Z 3、Z 4、Z 5、Z 6、Z 7各自独立地选自氢、卤素或C 1-C 4烷基； Z 1 , Z 2 , Z 3 , Z 4 , Z 5 , Z 6 , and Z 7 are each independently selected from hydrogen, halogen or C 1 -C 4 alkyl;
R 1选自氢、羟基、巯基、氨基、氰基、C 1-C 4烷基、C 1-C 4烷氧基、卤代C 1-C 4烷氧基、C 1-C 4烷硫基、卤代C 1-C 4烷硫基、C 1-C 4烷基氨基或C 1-C 4二烷基氨基； R 1 is selected from hydrogen, hydroxyl, mercapto, amino, cyano, C 1 -C 4 alkyl, C 1 -C 4 alkoxy, halogenated C 1 -C 4 alkoxy, C 1 -C 4 alkyl sulfide Group, halogenated C 1 -C 4 alkylthio, C 1 -C 4 alkylamino or C 1 -C 4 dialkylamino;
R 2选自氢、C 1-C 4烷基、卤代C 1-C 4烷基、氰基C 1-C 4烷基、C 1-C 4烷基羰基、C 3-C 6环烷基羰基或C 1-C 4烷氧基羰基； R 2 is selected from hydrogen, C 1 -C 4 alkyl, halogenated C 1 -C 4 alkyl, cyano C 1 -C 4 alkyl, C 1 -C 4 alkylcarbonyl, C 3 -C 6 cycloalkane Carbonyl or C 1 -C 4 alkoxycarbonyl;
或通式I化合物与盐酸、氢溴酸、硫酸、磷酸、甲酸、乙酸、丙酸、丁酸、戊酸、三氟乙酸、草酸、丙二酸、甲磺酸、4-甲苯磺酸、苹果酸、富马酸、乳酸、马来酸、水杨酸、酒石酸或柠檬酸形成的盐。Or a compound of general formula I and hydrochloric acid, hydrobromic acid, sulfuric acid, phosphoric acid, formic acid, acetic acid, propionic acid, butyric acid, valeric acid, trifluoroacetic acid, oxalic acid, malonic acid, methanesulfonic acid, 4-toluenesulfonic acid, apple Salts of acid, fumaric acid, lactic acid, maleic acid, salicylic acid, tartaric acid or citric acid.
通式I化合物作为杀细菌剂的应用时进一步优选的化合物为：When the compound of general formula I is used as a bactericide, further preferred compounds are:
n选自0或1；n is selected from 0 or 1;
W选自W 1-W 10所示基团之一： W is selected from one of the groups represented by W 1 -W 10 :
X 1、X 2、X 3、X 4、X 5各自独立地选自氢、氟、氯、溴、氰基、硝基、羟基、巯基、氨基、羧基、甲基、乙基、正丙基、异丙基、正丁基、异丁基、仲丁基、叔丁基、一氯甲基、二氯甲基、三氯甲基、一溴甲基、二溴甲基、三溴甲基、一氟甲基、二氟甲基、三氟甲基、2,2,2-三氟乙基、七氟异丙基、甲氧基、乙氧基、正丙氧基、异丙氧基、二氟甲氧基、三氟甲氧基、甲硫基、乙硫基、三氟甲硫基、2,2,2-三氟乙硫基、甲氨基、乙氨基、N,N-二甲基氨基、-NHCH＝C(CN) 2或-CH 2NHCH＝C(CN) 2； X 1 , X 2 , X 3 , X 4 , and X 5 are each independently selected from hydrogen, fluorine, chlorine, bromine, cyano, nitro, hydroxyl, mercapto, amino, carboxy, methyl, ethyl, n-propyl , Isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, monochloromethyl, dichloromethyl, trichloromethyl, monobromomethyl, dibromomethyl, tribromomethyl , Monofluoromethyl, difluoromethyl, trifluoromethyl, 2,2,2-trifluoroethyl, heptafluoroisopropyl, methoxy, ethoxy, n-propoxy, isopropoxy , Difluoromethoxy, trifluoromethoxy, methylthio, ethylthio, trifluoromethylthio, 2,2,2-trifluoroethylthio, methylamino, ethylamino, N,N-di Methylamino, -NHCH=C(CN) 2 or -CH 2 NHCH=C(CN) 2 ;
Y 1、Y 2、Y 3、Y 4各自独立地选自氢、氟、氯、溴、氰基、甲基、乙基、正丙基、异丙基、正丁基、异丁基、仲丁基、叔丁基、一氯甲基、二氯甲基、三氯甲基、一溴甲基、二溴甲基、三溴甲基、一氟甲基、二氟甲基、三氟甲基、2,2,2-三氟乙基、七氟异丙基、甲氧基、乙氧基、正丙氧基、异丙氧基、二氟甲氧基、三氟甲氧基、甲硫基、乙硫基、三氟甲硫基或2,2,2-三氟乙硫基； Y 1 , Y 2 , Y 3 , and Y 4 are each independently selected from hydrogen, fluorine, chlorine, bromine, cyano, methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec Butyl, tert-butyl, monochloromethyl, dichloromethyl, trichloromethyl, monobromomethyl, dibromomethyl, tribromomethyl, monofluoromethyl, difluoromethyl, trifluoromethyl Group, 2,2,2-trifluoroethyl, heptafluoroisopropyl, methoxy, ethoxy, n-propoxy, isopropoxy, difluoromethoxy, trifluoromethoxy, methyl Thio, ethylthio, trifluoromethylthio or 2,2,2-trifluoroethylthio;
Z 1、Z 2、Z 3、Z 4、Z 5、Z 6、Z 7各自独立地选自氢、氟、氯、溴、甲基、乙基、正丙基、异丙基、正丁基、异丁基、仲丁基或叔丁基； Z 1 , Z 2 , Z 3 , Z 4 , Z 5 , Z 6 , and Z 7 are each independently selected from hydrogen, fluorine, chlorine, bromine, methyl, ethyl, n-propyl, isopropyl, n-butyl , Isobutyl, sec-butyl or tert-butyl;
R 1选自氢、羟基、巯基、氨基、氰基、甲基、乙基、正丙基、正丁基、甲氧基、乙氧基、正丙氧基、异丙氧基、正丁氧基、甲硫基、乙硫基、正丙硫基、正丁硫基、甲氨基、乙氨基、正丙氨基或正丁氨基； R 1 is selected from hydrogen, hydroxyl, mercapto, amino, cyano, methyl, ethyl, n-propyl, n-butyl, methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy Group, methylthio, ethylthio, n-propylthio, n-butylthio, methylamino, ethylamino, n-propylamino or n-butylamino;
R 2选自氢、甲基、乙基、正丙基、异丙基、正丁基、异丁基、仲丁基、叔丁基、氰甲基、2,2,2-三氟乙基、乙酰基、正丙酰基、环丙基甲酰基、甲氧基羰基、乙氧基羰基、正丙氧基羰基或正丁氧基羰基； R 2 is selected from hydrogen, methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, cyanomethyl, 2,2,2-trifluoroethyl , Acetyl, n-propionyl, cyclopropylformyl, methoxycarbonyl, ethoxycarbonyl, n-propoxycarbonyl or n-butoxycarbonyl;
或通式I化合物与盐酸、氢溴酸、硫酸、磷酸、甲酸、乙酸、丙酸、丁酸、戊酸、三氟乙酸、草酸、丙二酸、甲磺酸、4-甲苯磺酸、苹果酸、富马酸、乳酸、马来酸、水杨酸、酒石酸或柠檬酸形成的盐。Or a compound of general formula I and hydrochloric acid, hydrobromic acid, sulfuric acid, phosphoric acid, formic acid, acetic acid, propionic acid, butyric acid, valeric acid, trifluoroacetic acid, oxalic acid, malonic acid, methanesulfonic acid, 4-toluenesulfonic acid, apple Salts of acid, fumaric acid, lactic acid, maleic acid, salicylic acid, tartaric acid or citric acid.
通式I化合物作为杀细菌剂的应用时更进一步优选的化合物为：When the compound of general formula I is used as a bactericide, further preferred compounds are:
n选自0或1；n is selected from 0 or 1;
W选自W 1-W 10所示基团之一： W is selected from one of the groups represented by W 1 -W 10 :
X 1、X 2、X 3、X 4、X 5各自独立地选自氢、氟、氯、溴、氰基、硝基、羟基、巯基、氨基、羧基、甲基、乙基、正丙基、异丙基、正丁基、异丁基、仲丁基、叔丁基、三氟甲基、甲氧基、乙氧基、三氟甲氧基、甲硫基、甲氨基、N,N-二甲基氨基、-NHCH＝C(CN) 2或-CH 2NHCH＝C(CN) 2； X 1 , X 2 , X 3 , X 4 , and X 5 are each independently selected from hydrogen, fluorine, chlorine, bromine, cyano, nitro, hydroxyl, mercapto, amino, carboxy, methyl, ethyl, n-propyl , Isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, trifluoromethyl, methoxy, ethoxy, trifluoromethoxy, methylthio, methylamino, N, N -Dimethylamino, -NHCH=C(CN) 2 or -CH 2 NHCH=C(CN) 2 ;
Y 1、Y 2、Y 3、Y 4选自氢； Y 1 , Y 2 , Y 3 , and Y 4 are selected from hydrogen;
Z 1、Z 2、Z 3、Z 4、Z 5、Z 6、Z 7选自氢； Z 1 , Z 2 , Z 3 , Z 4 , Z 5 , Z 6 , and Z 7 are selected from hydrogen;
R 1选自氢、氨基、甲基、甲氧基、乙氧基、甲硫基、乙硫基、甲氨基或乙氨基； R 1 is selected from hydrogen, amino, methyl, methoxy, ethoxy, methylthio, ethylthio, methylamino or ethylamino;
R 2选自氢、甲基、乙基、2,2,2-三氟乙基、氰甲基、乙酰基、正丙酰基、环丙基甲酰基、甲氧基羰基或乙氧基羰基； R 2 is selected from hydrogen, methyl, ethyl, 2,2,2-trifluoroethyl, cyanomethyl, acetyl, n-propionyl, cyclopropylformyl, methoxycarbonyl or ethoxycarbonyl;
或通式I化合物与盐酸、氢溴酸、硫酸、磷酸、甲酸、乙酸、丙酸、丁酸、戊酸、三氟乙酸、草酸、丙二酸、甲磺酸、4-甲苯磺酸、苹果酸、富马酸、乳酸、马来酸、水杨酸、酒石酸或柠檬酸形成的盐。Or a compound of general formula I and hydrochloric acid, hydrobromic acid, sulfuric acid, phosphoric acid, formic acid, acetic acid, propionic acid, butyric acid, valeric acid, trifluoroacetic acid, oxalic acid, malonic acid, methanesulfonic acid, 4-toluenesulfonic acid, apple Salts of acid, fumaric acid, lactic acid, maleic acid, salicylic acid, tartaric acid or citric acid.
上面给出的通式化合物的定义中，汇集所用术语一般代表如下取代基：In the definitions of compounds of the general formula given above, the terms used in pooling generally represent the following substituents:
卤素：指氟、氯、溴或碘。Halogen: refers to fluorine, chlorine, bromine or iodine.
烷基：直链或支链烷基，例如甲基、乙基、正丙基、异丙基或不同的丁基、戊基或己基异构体等。Alkyl: straight or branched chain alkyl, such as methyl, ethyl, n-propyl, isopropyl or different butyl, pentyl or hexyl isomers.
卤代烷基：直链或支链烷基，在这些烷基上的氢原子可部分或全部被卤素所取代，例如一氯甲基、二氯甲基、三氯甲基、一溴甲基、二溴甲基、三溴甲基、一氟甲基、二氟甲基、三氟甲基、2,2,2-三氟乙基、七氟异丙基等。Halogenated alkyl groups: straight or branched chain alkyl groups. The hydrogen atoms on these alkyl groups can be partially or completely replaced by halogens, such as monochloromethyl, dichloromethyl, trichloromethyl, monobromomethyl, and dichloromethyl. Bromomethyl, tribromomethyl, monofluoromethyl, difluoromethyl, trifluoromethyl, 2,2,2-trifluoroethyl, heptafluoroisopropyl, etc.
氰基烷基：直链或支链烷基，在这些烷基上的氢原子可部分或全部被氰基所取代，例如氰甲基(CNCH 2-)、氰乙基(CNCH 2CH 2-)、CNCH 2CH 2CH 2-、CNCH 2CH 2CH 2CH 2-等。 Cyanoalkyl: straight or branched chain alkyl groups, the hydrogen atoms on these alkyl groups can be partially or completely replaced by cyano groups, such as cyanomethyl (CNCH 2 -), cyanoethyl (CNCH 2 CH 2- ), CNCH 2 CH 2 CH 2 -, CNCH 2 CH 2 CH 2 CH 2 -etc.
烷氧基：直链或支链烷基，经氧原子键连接到结构上，例如甲氧基、乙氧基、正丙氧基、异丙氧基、正丁氧基、叔丁氧基等。Alkoxy: straight or branched chain alkyl, connected to the structure via oxygen atom bond, such as methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy, tert-butoxy, etc. .
卤代烷氧基：直链或支链烷氧基，在这些烷氧基上的氢原子可部分或全部被卤素所取代，例如氯甲氧基、二氯甲氧基、三氯甲氧基、氟甲氧基、二氟甲氧基、三氟甲氧基、氯氟甲氧基、2,2,2-三氟乙氧基等。Halogenated alkoxy groups: straight or branched chain alkoxy groups, the hydrogen atoms on these alkoxy groups can be partially or completely replaced by halogens, such as chloromethoxy, dichloromethoxy, trichloromethoxy, fluorine Methoxy, difluoromethoxy, trifluoromethoxy, chlorofluoromethoxy, 2,2,2-trifluoroethoxy, etc.
烷硫基：直链或支链烷基，经硫原子键连接到结构上，例如甲硫基、乙硫基等。Alkylthio: straight or branched chain alkyl, connected to the structure via a sulfur atom bond, such as methylthio, ethylthio and the like.
卤代烷硫基：直链或支链烷硫基，在这些烷硫基上的氢原子可部分或全部被卤素所取代，例如二氟甲硫基、三氟甲硫基、2,2,2-三氟乙硫基等。Halogenated alkylthio: linear or branched alkylthio, the hydrogen atoms on these alkylthio groups can be partially or completely replaced by halogen, such as difluoromethylthio, trifluoromethylthio, 2,2,2- Trifluoroethylthio and so on.
烷基氨基：直链或支链烷基，经氮原子键连接到结构上，例如甲氨基、乙氨基、正丙基氨基、异丙基氨基或同分异构的丁基胺。Alkylamino: straight or branched chain alkyl, connected to the structure via a nitrogen atom bond, such as methylamino, ethylamino, n-propylamino, isopropylamino or isomeric butylamine.
二烷基氨基：两个相同或不同的直链或支链烷基，经氮原子键连接到结构上，例如N,N-二甲基氨基、N-甲基-N-乙基氨基等。Dialkylamino: Two identical or different linear or branched alkyl groups are connected to the structure via a nitrogen atom bond, such as N,N-dimethylamino, N-methyl-N-ethylamino, etc.
烷基羰基：烷基经羰基连接到结构上，例如乙酰基(CH3CO-)，正丙酰基(CH3CH2CO-)等。Alkylcarbonyl: The alkyl group is connected to the structure via the carbonyl group, such as acetyl (CH3CO-), n-propionyl (CH3CH2CO-) and so on.
环烷基羰基：环烷基经羰基连接到结构上，例如环丙基甲酰基。Cycloalkylcarbonyl: Cycloalkyl is attached to the structure via a carbonyl group, such as cyclopropylformyl.
烷氧基羰基：烷基-O-CO-，例如甲氧基羰基(CH 3OCO-)、乙氧基羰基(CH 3CH 2OCO-)、正丙氧基羰基(CH 3CH 2CH 2OCO-)、正丁氧基羰基(CH 3CH 2CH 2CH 2OCO-)等。 Alkoxycarbonyl: alkyl-O-CO-, such as methoxycarbonyl (CH 3 OCO-), ethoxycarbonyl (CH 3 CH 2 OCO-), n-propoxycarbonyl (CH 3 CH 2 CH 2 OCO-), n-butoxycarbonyl (CH 3 CH 2 CH 2 CH 2 OCO-), etc.
本发明部分通式I化合物如表1～表218所示，但本发明绝非仅限于这些化合物。Some of the compounds of general formula I of the present invention are shown in Table 1 to Table 218, but the present invention is by no means limited to these compounds.
通式I中，当W＝W 1且n＝1时，通式I化合物以通式I-W 1-1表示(为便于叙述，W 1的取代基X 1、X 2、X 3、X 4、X 5以R表示，下同)。 Formula I, where W = W 1, and n = 1, compounds of Formula I represented by the formula IW 1 -1 (for ease of description, W substituent X 1, X 2 1 a, X 3, X 4, X 5 is represented by R, the same below).
Figure PCTCN2020073096-appb-000003
Figure PCTCN2020073096-appb-000003
表1：通式I-W 1-1中，当R 1＝R 2＝H时，R为不同的取代基见表1，代表化合物编号为1.1-1.360。 Table 1: In the general formula IW 1 -1, when R 1 =R 2 =H, R is a different substituent. See Table 1, which represents compound numbers from 1.1-1.360.
表1Table 1
Figure PCTCN2020073096-appb-000004
Figure PCTCN2020073096-appb-000004
Figure PCTCN2020073096-appb-000005
Figure PCTCN2020073096-appb-000005
Figure PCTCN2020073096-appb-000006
Figure PCTCN2020073096-appb-000006
表2：通式I-W 1-1中，当R 1＝CH 3且R 2＝H时，取代基R与表1一致，代表化合物编号为2.1-2.360，依次对应表1的1.1-1.360。 Table 2: In the general formula IW 1 -1, when R 1 =CH 3 and R 2 =H, the substituent R is consistent with Table 1, and represents the compound number 2.1-2.360, corresponding to 1.1-1.360 of Table 1 in turn.
表3：通式I-W 1-1中，当R 1＝CH 2CH 3且R 2＝H时，取代基R与表1一致，代表化合物编号为3.1-3.360，依次对应表1的1.1-1.360。 Table 3: In the general formula IW 1 -1, when R 1 ＝CH 2 CH 3 and R 2 ＝H, the substituent R is consistent with Table 1, and the representative compound number is 3.1-3.360, corresponding to 1.1-1.360 of Table 1 in turn .
表4：通式I-W 1-1中，当R 1＝SCH 3且R 2＝H时，取代基R与表1一致，代表化合物编号为4.1-4.360，依次对应表1的1.1-1.360。 Table 4: In the general formula IW 1 -1, when R 1 =SCH 3 and R 2 =H, the substituent R is consistent with Table 1, and the representative compound number is 4.1-4.360, corresponding to 1.1-1.360 of Table 1 in turn.
表5：通式I-W 1-1中，当R 1＝SCH 2CH 3且R 2＝H时，取代基R与表1一致，代表化 合物编号为5.1-5.360，依次对应表1的1.1-1.360。 Table 5: In the general formula IW 1 -1, when R 1 =SCH 2 CH 3 and R 2 =H, the substituent R is consistent with Table 1, and the representative compound number is 5.1-5.360, corresponding to 1.1-1.360 in Table 1 in turn .
表6：通式I-W 1-1中，当R 1＝NH 2且R 2＝H时，取代基R与表1一致，代表化合物编号为6.1-6.360，依次对应表1的1.1-1.360。 Table 6: In the general formula IW 1 -1, when R 1 =NH 2 and R 2 =H, the substituent R is consistent with Table 1, and the representative compound number is 6.1-6.360, corresponding to 1.1-1.360 of Table 1 in turn.
表7：通式I-W 1-1中，当R 1＝NHCH 3且R 2＝H时，取代基R与表1一致，代表化合物编号为7.1-7.360，依次对应表1的1.1-1.360。 Table 7: In the general formula IW 1 -1, when R 1 =NHCH 3 and R 2 =H, the substituent R is consistent with Table 1, and the representative compound number is 7.1-7.360, corresponding to 1.1-1.360 of Table 1 in turn.
表8：通式I-W 1-1中，当R 1＝NHCH 2CH 3且R 2＝H时，取代基R与表1一致，代表化合物编号为8.1-8.360，依次对应表1的1.1-1.360。 Table 8: In the general formula IW 1 -1, when R 1 =NHCH 2 CH 3 and R 2 =H, the substituent R is consistent with Table 1, and the representative compound number is 8.1-8.360, corresponding to 1.1-1.360 of Table 1 in turn .
表9：通式I-W 1-1中，当R 1＝N(CH 3) 2且R 2＝H时，取代基R与表1一致，代表化合物编号为9.1-9.360，依次对应表1的1.1-1.360。 Table 9: In the general formula IW 1 -1, when R 1 =N(CH 3 ) 2 and R 2 =H, the substituent R is consistent with Table 1, which represents the compound number 9.1-9.360, corresponding to 1.1 in Table 1 in turn -1.360.
表10：通式I-W 1-1中，当R 1＝OCH 3且R 2＝H时，取代基R与表1一致，代表化合物编号为10.1-10.360，依次对应表1的1.1-1.360。 Table 10: In the general formula IW 1 -1, when R 1 =OCH 3 and R 2 =H, the substituent R is consistent with Table 1, and the representative compound numbers are 10.1-10.360, corresponding to 1.1-1.360 in Table 1 in turn.
表11：通式I-W 1-1中，当R 1＝OCH 2CH 3且R 2＝H时，取代基R与表1一致，代表化合物编号为11.1-11.360，依次对应表1的1.1-1.360。 Table 11: In the general formula IW 1 -1, when R 1 ＝OCH 2 CH 3 and R 2 ＝H, the substituent R is consistent with Table 1, and the representative compound number is 11.1-11.360, corresponding to 1.1-1.360 in Table 1 in turn .
表12：通式I-W 1-1中，当R 1＝H且R 2＝CH 3时，取代基R与表1一致，代表化合物编号为12.1-12.360，依次对应表1的1.1-1.360。 Table 12: In the general formula IW 1 -1, when R 1 =H and R 2 =CH 3 , the substituent R is consistent with Table 1, and the representative compound number is 12.1-12.360, corresponding to 1.1-1.360 of Table 1 in turn.
表13：通式I-W 1-1中，当R 1＝CH 3且R 2＝CH 3时，取代基R与表1一致，代表化合物编号为13.1-13.360，依次对应表1的1.1-1.360。 Table 13: In the general formula IW 1 -1, when R 1 =CH 3 and R 2 =CH 3 , the substituent R is consistent with Table 1, and the representative compound numbers are 13.1-13.360, corresponding to 1.1-1.360 in Table 1 in turn.
表14：通式I-W 1-1中，当R 1＝CH 2CH 3且R 2＝CH 3时，取代基R与表1一致，代表化合物编号为14.1-14.360，依次对应表1的1.1-1.360。 Table 14: In the general formula IW 1 -1, when R 1 ＝CH 2 CH 3 and R 2 ＝CH 3 , the substituent R is consistent with Table 1, and the representative compound number is 14.1-14.360, corresponding to 1.1- in Table 1 in turn 1.360.
表15：通式I-W 1-1中，当R 1＝SCH 3且R 2＝CH 3时，取代基R与表1一致，代表化合物编号为15.1-15.360，依次对应表1的1.1-1.360。 Table 15: In the general formula IW 1 -1, when R 1 =SCH 3 and R 2 =CH 3 , the substituent R is consistent with Table 1, and the representative compound number is 15.1-15.360, corresponding to 1.1-1.360 of Table 1 in turn.
表16：通式I-W 1-1中，当R 1＝SCH 2CH 3且R 2＝CH 3时，取代基R与表1一致，代表化合物编号为16.1-16.360，依次对应表1的1.1-1.360。 Table 16: In the general formula IW 1 -1, when R 1 =SCH 2 CH 3 and R 2 =CH 3 , the substituent R is consistent with Table 1, and the representative compound number is 16.1-16.360, corresponding to 1.1- in Table 1 in turn 1.360.
表17：通式I-W 1-1中，当R 1＝NH 2且R 2＝CH 3时，取代基R与表1一致，代表化合物编号为17.1-17.360，依次对应表1的1.1-1.360。 Table 17: In the general formula IW 1 -1, when R 1 =NH 2 and R 2 =CH 3 , the substituent R is consistent with Table 1, and the representative compound number is 17.1-17.360, corresponding to 1.1-1.360 of Table 1 in turn.
表18：通式I-W 1-1中，当R 1＝NHCH 3且R 2＝CH 3时，取代基R与表1一致，代表化合物编号为18.1-18.360，依次对应表1的1.1-1.360。 Table 18: In the general formula IW 1 -1, when R 1 =NHCH 3 and R 2 =CH 3 , the substituent R is consistent with Table 1, and the representative compound number is 18.1-18.360, corresponding to 1.1-1.360 of Table 1 in turn.
表19：通式I-W 1-1中，当R 1＝NHCH 2CH 3且R 2＝CH 3时，取代基R与表1一致，代表化合物编号为19.1-19.360，依次对应表1的1.1-1.360。 Table 19: In the general formula IW 1 -1, when R 1 =NHCH 2 CH 3 and R 2 =CH 3 , the substituent R is consistent with Table 1, which represents compound numbers 19.1-19.360, corresponding to 1.1- in Table 1 in turn 1.360.
表20：通式I-W 1-1中，当R 1＝N(CH 3) 2且R 2＝CH 3时，取代基R与表1一致，代表化合物编号为20.1-20.360，依次对应表1的1.1-1.360。 Table 20: In the general formula IW 1 -1, when R 1 ＝N(CH 3 ) 2 and R 2 ＝CH 3 , the substituent R is consistent with Table 1, and represents the compound number of 20.1-20.360, corresponding to Table 1 in turn 1.1-1.360.
表21：通式I-W 1-1中，当R 1＝OCH 3且R 2＝CH 3时，取代基R与表1一致，代表化合物编号为21.1-21.360，依次对应表1的1.1-1.360。 Table 21: In the general formula IW 1 -1, when R 1 =OCH 3 and R 2 =CH 3 , the substituent R is consistent with Table 1, and the representative compound number is 21.1-21.360, corresponding to 1.1-1.360 of Table 1 in turn.
表22：通式I-W 1-1中，当R 1＝OCH 2CH 3且R 2＝CH 3时，取代基R与表1一致，代表化合物编号为22.1-22.360，依次对应表1的1.1-1.360。 Table 22: In the general formula IW 1 -1, when R 1 ═OCH 2 CH 3 and R 2 ═CH 3 , the substituent R is consistent with Table 1, which represents the compound number 22.1-22.360, corresponding to 1.1- in Table 1 in turn 1.360.
表23：通式I-W 1-1中，当R 1＝H且R 2＝CH 2CH 3时，取代基R与表1一致，代表化合物编号为23.1-23.360，依次对应表1的1.1-1.360。 Table 23: In the general formula IW 1 -1, when R 1 =H and R 2 =CH 2 CH 3 , the substituent R is consistent with Table 1, and the representative compound number is 23.1-23.360, corresponding to 1.1-1.360 in Table 1 in turn .
表24：通式I-W 1-1中，当R 1＝CH 3且R 2＝CH 2CH 3时，取代基R与表1一致，代表化合物编号为24.1-24.360，依次对应表1的1.1-1.360。 Table 24: In the general formula IW 1 -1, when R 1 ＝CH 3 and R 2 ＝CH 2 CH 3 , the substituent R is consistent with Table 1, and the representative compound number is 24.1-24.360, corresponding to 1.1- in Table 1 in turn 1.360.
表25：通式I-W 1-1中，当R 1＝CH 2CH 3且R 2＝CH 2CH 3时，取代基R与表1一致，代表化合物编号为25.1-25.360，依次对应表1的1.1-1.360。 Table 25: In the general formula IW 1 -1, when R 1 ＝CH 2 CH 3 and R 2 ＝CH 2 CH 3 , the substituent R is consistent with Table 1, which represents compound numbers 25.1-25.360, corresponding to those in Table 1. 1.1-1.360.
表26：通式I-W 1-1中，当R 1＝SCH 3且R 2＝CH 2CH 3时，取代基R与表1一致，代表化合物编号为26.1-26.360，依次对应表1的1.1-1.360。 Table 26: In the general formula IW 1 -1, when R 1 =SCH 3 and R 2 =CH 2 CH 3 , the substituent R is consistent with Table 1, and the representative compound number is 26.1-26.360, corresponding to 1.1- in Table 1. 1.360.
表27：通式I-W 1-1中，当R 1＝SCH 2CH 3且R 2＝CH 2CH 3时，取代基R与表1一致， 代表化合物编号为27.1-27.360，依次对应表1的1.1-1.360。 Table 27: In the general formula IW 1 -1, when R 1 =SCH 2 CH 3 and R 2 =CH 2 CH 3 , the substituent R is consistent with Table 1, which represents the compound number 27.1-27.360, corresponding to Table 1 in turn 1.1-1.360.
表28：通式I-W 1-1中，当R 1＝NH 2且R 2＝CH 2CH 3时，取代基R与表1一致，代表化合物编号为28.1-28.360，依次对应表1的1.1-1.360。 Table 28: In the general formula IW 1 -1, when R 1 =NH 2 and R 2 =CH 2 CH 3 , the substituent R is consistent with Table 1, and the representative compound number is 28.1-28.360, corresponding to 1.1- in Table 1 in turn 1.360.
表29：通式I-W 1-1中，当R 1＝NHCH 3且R 2＝CH 2CH 3时，取代基R与表1一致，代表化合物编号为29.1-29.360，依次对应表1的1.1-1.360。 Table 29: In the general formula IW 1 -1, when R 1 =NHCH 3 and R 2 =CH 2 CH 3 , the substituent R is consistent with Table 1, which represents the compound number 29.1-29.360, corresponding to 1.1- in Table 1 in turn 1.360.
表30：通式I-W 1-1中，当R 1＝NHCH 2CH 3且R 2＝CH 2CH 3时，取代基R与表1一致，代表化合物编号为30.1-30.360，依次对应表1的1.1-1.360。 Table 30: In the general formula IW 1 -1, when R 1 ＝NHCH 2 CH 3 and R 2 ＝CH 2 CH 3 , the substituent R is consistent with Table 1, which represents the compound number of 30.1-30.360, corresponding to Table 1 in turn 1.1-1.360.
表31：通式I-W 1-1中，当R 1＝N(CH 3) 2且R 2＝CH 2CH 3时，取代基R与表1一致，代表化合物编号为31.1-31.360，依次对应表1的1.1-1.360。 Table 31: In the general formula IW 1 -1, when R 1 ＝N(CH 3 ) 2 and R 2 ＝CH 2 CH 3 , the substituent R is consistent with Table 1, which represents compound numbers 31.1-31.360, corresponding to the table in turn 1 of 1.1-1.360.
表32：通式I-W 1-1中，当R 1＝OCH 3且R 2＝CH 2CH 3时，取代基R与表1一致，代表化合物编号为32.1-32.360，依次对应表1的1.1-1.360。 Table 32: In the general formula IW 1 -1, when R 1 ═OCH 3 and R 2 ═CH 2 CH 3 , the substituent R is consistent with Table 1, and the representative compound number is 32.1-32.360, corresponding to 1.1- in Table 1 in turn 1.360.
表33：通式I-W 1-1中，当R 1＝OCH 2CH 3且R 2＝CH 2CH 3时，取代基R与表1一致，代表化合物编号为33.1-33.360，依次对应表1的1.1-1.360。 Table 33: In the general formula IW 1 -1, when R 1 ＝OCH 2 CH 3 and R 2 ＝CH 2 CH 3 , the substituent R is consistent with Table 1, and represents the compound number 33.1-33.360, which corresponds to that in Table 1. 1.1-1.360.
表34：通式I-W 1-1中，当R 1＝H且R 2＝CH 2CN时，取代基R与表1一致，代表化合物编号为34.1-34.360，依次对应表1的1.1-1.360。 Table 34: In the general formula IW 1 -1, when R 1 =H and R 2 =CH 2 CN, the substituent R is consistent with Table 1, and the representative compound number is 34.1-34.360, corresponding to 1.1-1.360 of Table 1 in turn.
表35：通式I-W 1-1中，当R 1＝CH 3且R 2＝CH 2CN时，取代基R与表1一致，代表化合物编号为35.1-35.360，依次对应表1的1.1-1.360。 Table 35: In the general formula IW 1 -1, when R 1 =CH 3 and R 2 =CH 2 CN, the substituent R is consistent with Table 1, and the representative compound number is 35.1-35.360, corresponding to 1.1-1.360 in Table 1 in turn .
表36：通式I-W 1-1中，当R 1＝CH 2CH 3且R 2＝CH 2CN时，取代基R与表1一致，代表化合物编号为36.1-36.360，依次对应表1的1.1-1.360。 Table 36: In the general formula IW 1 -1, when R 1 =CH 2 CH 3 and R 2 =CH 2 CN, the substituent R is consistent with Table 1, which represents the compound number 36.1-36.360, corresponding to 1.1 in Table 1. -1.360.
表37：通式I-W 1-1中，当R 1＝SCH 3且R 2＝CH 2CN时，取代基R与表1一致，代表化合物编号为37.1-37.360，依次对应表1的1.1-1.360。 Table 37: In the general formula IW 1 -1, when R 1 =SCH 3 and R 2 =CH 2 CN, the substituent R is consistent with Table 1, and the representative compound number is 37.1-37.360, corresponding to 1.1-1.360 in Table 1 in turn .
表38：通式I-W 1-1中，当R 1＝SCH 2CH 3且R 2＝CH 2CN时，取代基R与表1一致，代表化合物编号为38.1-38.360，依次对应表1的1.1-1.360。 Table 38: In the general formula IW 1 -1, when R 1 =SCH 2 CH 3 and R 2 =CH 2 CN, the substituent R is consistent with Table 1, and the representative compound number is 38.1-38.360, corresponding to 1.1 in Table 1. -1.360.
表39：通式I-W 1-1中，当R 1＝NH 2且R 2＝CH 2CN时，取代基R与表1一致，代表化合物编号为39.1-39.360，依次对应表1的1.1-1.360。 Table 39: In the general formula IW 1 -1, when R 1 =NH 2 and R 2 =CH 2 CN, the substituent R is consistent with Table 1, and the representative compound number is 39.1-39.360, corresponding to 1.1-1.360 in Table 1 in turn .
表40：通式I-W 1-1中，当R 1＝NHCH 3且R 2＝CH 2CN时，取代基R与表1一致，代表化合物编号为40.1-40.360，依次对应表1的1.1-1.360。 Table 40: In the general formula IW 1 -1, when R 1 =NHCH 3 and R 2 =CH 2 CN, the substituent R is consistent with Table 1, and the representative compound number is 40.1-40.360, corresponding to 1.1-1.360 in Table 1 in turn .
表41：通式I-W 1-1中，当R 1＝NHCH 2CH 3且R 2＝CH 2CN时，取代基R与表1一致，代表化合物编号为41.1-41.360，依次对应表1的1.1-1.360。 Table 41: In the general formula IW 1 -1, when R 1 =NHCH 2 CH 3 and R 2 =CH 2 CN, the substituent R is consistent with Table 1, which represents the compound number 41.1-41.360, corresponding to 1.1 in Table 1 in turn -1.360.
表42：通式I-W 1-1中，当R 1＝N(CH 3) 2且R 2＝CH 2CN时，取代基R与表1一致，代表化合物编号为42.1-42.360，依次对应表1的1.1-1.360。 Table 42: In the general formula IW 1 -1, when R 1 ＝N(CH 3 ) 2 and R 2 ＝CH 2 CN, the substituent R is consistent with Table 1, which represents compound numbers 42.1-42.360, corresponding to Table 1 in turn 1.1-1.360.
表43：通式I-W 1-1中，当R 1＝OCH 3且R 2＝CH 2CN时，取代基R与表1一致，代表化合物编号为43.1-43.360，依次对应表1的1.1-1.360。 Table 43: In the general formula IW 1 -1, when R 1 ═OCH 3 and R 2 ═CH 2 CN, the substituent R is consistent with Table 1, and the representative compound number is 43.1-43.360, corresponding to 1.1-1.360 in Table 1 in turn .
表44：通式I-W 1-1中，当R 1＝OCH 2CH 3且R 2＝CH 2CN时，取代基R与表1一致，代表化合物编号为44.1-44.360，依次对应表1的1.1-1.360。 Table 44: In the general formula IW 1 -1, when R 1 ＝OCH 2 CH 3 and R 2 ＝CH 2 CN, the substituent R is consistent with Table 1, which represents the compound number 44.1-44.360, corresponding to 1.1 in Table 1. -1.360.
表45：通式I-W 1-1中，当R 1＝H且R 2＝乙酰基时，取代基R与表1一致，代表化合物编号为45.1-45.360，依次对应表1的1.1-1.360。 Table 45: In the general formula IW 1 -1, when R 1 =H and R 2 =acetyl, the substituent R is consistent with Table 1, and the representative compound number is 45.1-45.360, corresponding to 1.1-1.360 of Table 1 in turn.
表46：通式I-W 1-1中，当R 1＝CH 3且R 2＝乙酰基时，取代基R与表1一致，代表化合物编号为46.1-46.360，依次对应表1的1.1-1.360。 Table 46: In the general formula IW 1 -1, when R 1 =CH 3 and R 2 =acetyl, the substituent R is consistent with Table 1, and the representative compound number is 46.1-46.360, corresponding to 1.1-1.360 of Table 1 in turn.
表47：通式I-W 1-1中，当R 1＝CH 2CH 3且R 2＝乙酰基时，取代基R与表1一致，代表化合物编号为47.1-47.360，依次对应表1的1.1-1.360。 Table 47: In the general formula IW 1 -1, when R 1 =CH 2 CH 3 and R 2 =acetyl, the substituent R is consistent with Table 1, and the representative compound number is 47.1-47.360, corresponding to 1.1- in Table 1 in turn 1.360.
表48：通式I-W 1-1中，当R 1＝SCH 3且R 2＝乙酰基时，取代基R与表1一致，代表化合物编号为48.1-48.360，依次对应表1的1.1-1.360。 Table 48: In the general formula IW 1 -1, when R 1 =SCH 3 and R 2 =acetyl, the substituent R is consistent with Table 1, and the representative compound number is 48.1-48.360, corresponding to 1.1-1.360 of Table 1 in turn.
表49：通式I-W 1-1中，当R 1＝SCH 2CH 3且R 2＝乙酰基时，取代基R与表1一致， 代表化合物编号为49.1-49.360，依次对应表1的1.1-1.360。 Table 49: In the general formula IW 1 -1, when R 1 =SCH 2 CH 3 and R 2 =acetyl, the substituent R is consistent with Table 1, and the representative compound number is 49.1-49.360, corresponding to 1.1- in Table 1 in turn 1.360.
表50：通式I-W 1-1中，当R 1＝NH 2且R 2＝乙酰基时，取代基R与表1一致，代表化合物编号为50.1-50.360，依次对应表1的1.1-1.360。 Table 50: In the general formula IW 1 -1, when R 1 =NH 2 and R 2 =acetyl, the substituent R is consistent with Table 1, and the representative compound number is 50.1-50.360, corresponding to 1.1-1.360 of Table 1 in turn.
表51：通式I-W 1-1中，当R 1＝NHCH 3且R 2＝乙酰基时，取代基R与表1一致，代表化合物编号为51.1-51.360，依次对应表1的1.1-1.360。 Table 51: In the general formula IW 1 -1, when R 1 =NHCH 3 and R 2 =acetyl, the substituent R is consistent with Table 1, and the representative compound number is 51.1-51.360, corresponding to 1.1-1.360 of Table 1 in turn.
表52：通式I-W 1-1中，当R 1＝NHCH 2CH 3且R 2＝乙酰基时，取代基R与表1一致，代表化合物编号为52.1-52.360，依次对应表1的1.1-1.360。 Table 52: In the general formula IW 1 -1, when R 1 =NHCH 2 CH 3 and R 2 =acetyl, the substituent R is consistent with Table 1, and the representative compound number is 52.1-52.360, corresponding to 1.1- in Table 1 in turn 1.360.
表53：通式I-W 1-1中，当R 1＝N(CH 3) 2且R 2＝乙酰基时，取代基R与表1一致，代表化合物编号为53.1-53.360，依次对应表1的1.1-1.360。 Table 53: In the general formula IW 1 -1, when R 1 =N(CH 3 ) 2 and R 2 =acetyl, the substituent R is consistent with Table 1, and represents the compound number of 53.1-53.360, corresponding to Table 1 in turn 1.1-1.360.
表54：通式I-W 1-1中，当R 1＝OCH 3且R 2＝乙酰基时，取代基R与表1一致，代表化合物编号为54.1-54.360，依次对应表1的1.1-1.360。 Table 54: In the general formula IW 1 -1, when R 1 =OCH 3 and R 2 =acetyl, the substituent R is consistent with Table 1, and the representative compound number is 54.1-54.360, corresponding to 1.1-1.360 in Table 1 in turn.
表55：通式I-W 1-1中，当R 1＝OCH 2CH 3且R 2＝乙酰基时，取代基R与表1一致，代表化合物编号为55.1-55.360，依次对应表1的1.1-1.360。 Table 55: In the general formula IW 1 -1, when R 1 =OCH 2 CH 3 and R 2 =acetyl, the substituent R is consistent with Table 1, and the representative compound number is 55.1-55.360, corresponding to 1.1- in Table 1. 1.360.
表56：通式I-W 1-1中，当R 1＝H且R 2＝正丙酰基时，取代基R与表1一致，代表化合物编号为56.1-56.360，依次对应表1的1.1-1.360。 Table 56: In the general formula IW 1 -1, when R 1 =H and R 2 =n-propionyl, the substituent R is consistent with Table 1, and the representative compound number is 56.1-56.360, corresponding to 1.1-1.360 in Table 1 in turn.
表57：通式I-W 1-1中，当R 1＝CH 3且R 2＝正丙酰基时，取代基R与表1一致，代表化合物编号为57.1-57.360，依次对应表1的1.1-1.360。 Table 57: In the general formula IW 1 -1, when R 1 =CH 3 and R 2 =n-propionyl, the substituent R is consistent with Table 1, and the representative compound number is 57.1-57.360, corresponding to 1.1-1.360 in Table 1 in turn .
表58：通式I-W 1-1中，当R 1＝CH 2CH 3且R 2＝正丙酰基时，取代基R与表1一致，代表化合物编号为58.1-58.360，依次对应表1的1.1-1.360。 Table 58: In the general formula IW 1 -1, when R 1 =CH 2 CH 3 and R 2 =n-propionyl, the substituent R is consistent with Table 1, and the representative compound number is 58.1-58.360, corresponding to 1.1 in Table 1. -1.360.
表59：通式I-W 1-1中，当R 1＝SCH 3且R 2＝正丙酰基时，取代基R与表1一致，代表化合物编号为59.1-59.360，依次对应表1的1.1-1.360。 Table 59: In the general formula IW 1 -1, when R 1 =SCH 3 and R 2 =n-propionyl, the substituent R is consistent with Table 1, and the representative compound number is 59.1-59.360, corresponding to 1.1-1.360 of Table 1 in turn .
表60：通式I-W 1-1中，当R 1＝SCH 2CH 3且R 2＝正丙酰基时，取代基R与表1一致，代表化合物编号为60.1-60.360，依次对应表1的1.1-1.360。 Table 60: In the general formula IW 1 -1, when R 1 =SCH 2 CH 3 and R 2 =n-propionyl, the substituent R is consistent with Table 1, and the representative compound number is 60.1-60.360, corresponding to 1.1 in Table 1 in turn -1.360.
表61：通式I-W 1-1中，当R 1＝NH 2且R 2＝正丙酰基时，取代基R与表1一致，代表化合物编号为61.1-61.360，依次对应表1的1.1-1.360。 Table 61: In the general formula IW 1 -1, when R 1 =NH 2 and R 2 = n-propionyl, the substituent R is consistent with Table 1, and the representative compound number is 61.1-61.360, corresponding to 1.1-1.360 of Table 1 in turn .
表62：通式I-W 1-1中，当R 1＝NHCH 3且R 2＝正丙酰基时，取代基R与表1一致，代表化合物编号为62.1-62.360，依次对应表1的1.1-1.360。 Table 62: In the general formula IW 1 -1, when R 1 =NHCH 3 and R 2 = n-propionyl, the substituent R is consistent with Table 1, and the representative compound number is 62.1-62.360, corresponding to 1.1-1.360 in Table 1 in turn .
表63：通式I-W 1-1中，当R 1＝NHCH 2CH 3且R 2＝正丙酰基时，取代基R与表1一致，代表化合物编号为63.1-63.360，依次对应表1的1.1-1.360。 Table 63: In the general formula IW 1 -1, when R 1 =NHCH 2 CH 3 and R 2 = n-propionyl, the substituent R is consistent with Table 1, representing the compound number of 63.1-63.360, corresponding to 1.1 in Table 1 in turn -1.360.
表64：通式I-W 1-1中，当R 1＝N(CH 3) 2且R 2＝正丙酰基时，取代基R与表1一致，代表化合物编号为64.1-64.360，依次对应表1的1.1-1.360。 Table 64: In the general formula IW 1 -1, when R 1 =N(CH 3 ) 2 and R 2 =n-propionyl, the substituent R is consistent with Table 1, which represents the compound number of 64.1-64.360, corresponding to Table 1 in turn 1.1-1.360.
表65：通式I-W 1-1中，当R 1＝OCH 3且R 2＝正丙酰基时，取代基R与表1一致，代表化合物编号为65.1-65.360，依次对应表1的1.1-1.360。 Table 65: In the general formula IW 1 -1, when R 1 =OCH 3 and R 2 =n-propionyl, the substituent R is consistent with Table 1, and the representative compound number is 65.1-65.360, corresponding to 1.1-1.360 in Table 1 in turn .
表66：通式I-W 1-1中，当R 1＝OCH 2CH 3且R 2＝正丙酰基时，取代基R与表1一致，代表化合物编号为66.1-66.360，依次对应表1的1.1-1.360。 Table 66: In the general formula IW 1 -1, when R 1 =OCH 2 CH 3 and R 2 =n-propionyl, the substituent R is consistent with Table 1, and represents the compound number 66.1-66.360, corresponding to 1.1 in Table 1 in turn -1.360.
表67：通式I-W 1-1中，当R 1＝H且R 2＝环丙基甲酰基时，取代基R与表1一致，代表化合物编号为67.1-67.360，依次对应表1的1.1-1.360。 Table 67: In the general formula IW 1 -1, when R 1 =H and R 2 =cyclopropylformyl, the substituent R is consistent with Table 1, and the representative compound number is 67.1-67.360, corresponding to 1.1- in Table 1 in turn 1.360.
表68：通式I-W 1-1中，当R 1＝CH 3且R 2＝环丙基甲酰基时，取代基R与表1一致，代表化合物编号为68.1-68.360，依次对应表1的1.1-1.360。 Table 68: In the general formula IW 1 -1, when R 1 =CH 3 and R 2 =cyclopropylformyl, the substituent R is consistent with Table 1, and the representative compound number is 68.1-68.360, corresponding to 1.1 in Table 1 in turn -1.360.
表69：通式I-W 1-1中，当R 1＝CH 2CH 3且R 2＝环丙基甲酰基时，取代基R与表1一致，代表化合物编号为69.1-69.360，依次对应表1的1.1-1.360。 Table 69: In the general formula IW 1 -1, when R 1 =CH 2 CH 3 and R 2 =cyclopropylformyl, the substituent R is consistent with Table 1, representing compound numbers 69.1-69.360, corresponding to Table 1 in turn 1.1-1.360.
表70：通式I-W 1-1中，当R 1＝SCH 3且R 2＝环丙基甲酰基时，取代基R与表1一致，代表化合物编号为70.1-70.360，依次对应表1的1.1-1.360。 Table 70: In the general formula IW 1 -1, when R 1 =SCH 3 and R 2 =cyclopropylformyl, the substituent R is consistent with Table 1, and the representative compound number is 70.1-70.360, corresponding to 1.1 in Table 1 in turn -1.360.
表71：通式I-W 1-1中，当R 1＝SCH 2CH 3且R 2＝环丙基甲酰基时，取代基R与表1 一致，代表化合物编号为71.1-71.360，依次对应表1的1.1-1.360。 Table 71: In the general formula IW 1 -1, when R 1 =SCH 2 CH 3 and R 2 =cyclopropylformyl, the substituent R is consistent with Table 1, representing compound numbers 71.1-71.360, corresponding to Table 1 in turn 1.1-1.360.
表72：通式I-W 1-1中，当R 1＝NH 2且R 2＝环丙基甲酰基时，取代基R与表1一致，代表化合物编号为72.1-72.360，依次对应表1的1.1-1.360。 Table 72: In the general formula IW 1 -1, when R 1 =NH 2 and R 2 =cyclopropylformyl, the substituent R is consistent with Table 1, and the representative compound number is 72.1-72.360, corresponding to 1.1 in Table 1 in turn -1.360.
表73：通式I-W 1-1中，当R 1＝NHCH 3且R 2＝环丙基甲酰基时，取代基R与表1一致，代表化合物编号为73.1-73.360，依次对应表1的1.1-1.360。 Table 73: In the general formula IW 1 -1, when R 1 =NHCH 3 and R 2 =cyclopropylformyl, the substituent R is consistent with Table 1, representing compound numbers 73.1-73.360, corresponding to 1.1 in Table 1 in turn -1.360.
表74：通式I-W 1-1中，当R 1＝NHCH 2CH 3且R 2＝环丙基甲酰基时，取代基R与表1一致，代表化合物编号为74.1-74.360，依次对应表1的1.1-1.360。 Table 74: In the general formula IW 1 -1, when R 1 =NHCH 2 CH 3 and R 2 =cyclopropylformyl, the substituent R is consistent with Table 1, which represents compound numbers 74.1-74.360, corresponding to Table 1 in turn 1.1-1.360.
表75：通式I-W 1-1中，当R 1＝N(CH 3) 2且R 2＝环丙基甲酰基时，取代基R与表1一致，代表化合物编号为75.1-75.360，依次对应表1的1.1-1.360。 Table 75: In the general formula IW 1 -1, when R 1 =N(CH 3 ) 2 and R 2 =cyclopropylformyl, the substituent R is consistent with Table 1, representing compound numbers 75.1-75.360, corresponding in turn Table 1. 1.1-1.360.
表76：通式I-W 1-1中，当R 1＝OCH 3且R 2＝环丙基甲酰基时，取代基R与表1一致，代表化合物编号为76.1-76.360，依次对应表1的1.1-1.360。 Table 76: In the general formula IW 1 -1, when R 1 =OCH 3 and R 2 =cyclopropylformyl, the substituent R is consistent with Table 1, representing compound numbers 76.1-76.360, corresponding to 1.1 in Table 1 in turn -1.360.
表77：通式I-W 1-1中，当R 1＝OCH 2CH 3且R 2＝环丙基甲酰基时，取代基R与表1一致，代表化合物编号为77.1-77.360，依次对应表1的1.1-1.360。 Table 77: In the general formula IW 1 -1, when R 1 =OCH 2 CH 3 and R 2 =cyclopropylformyl, the substituent R is consistent with Table 1, which represents compound numbers 77.1-77.360, corresponding to Table 1 in turn 1.1-1.360.
表78：通式I-W 1-1中，当R 1＝H且R 2＝甲氧基羰基时，取代基R与表1一致，代表化合物编号为78.1-78.360，依次对应表1的1.1-1.360。 Table 78: In the general formula IW 1 -1, when R 1 =H and R 2 =methoxycarbonyl, the substituent R is consistent with Table 1, and the representative compound number is 78.1-78.360, corresponding to 1.1-1.360 in Table 1 in turn .
表79：通式I-W 1-1中，当R 1＝CH 3且R 2＝甲氧基羰基时，取代基R与表1一致，代表化合物编号为79.1-79.360，依次对应表1的1.1-1.360。 Table 79: In the general formula IW 1 -1, when R 1 =CH 3 and R 2 =methoxycarbonyl, the substituent R is consistent with Table 1, and the representative compound number is 79.1-79.360, corresponding to 1.1- in Table 1 in turn 1.360.
表80：通式I-W 1-1中，当R 1＝CH 2CH 3且R 2＝甲氧基羰基时，取代基R与表1一致，代表化合物编号为80.1-80.360，依次对应表1的1.1-1.360。 Table 80: In the general formula IW 1 -1, when R 1 =CH 2 CH 3 and R 2 =methoxycarbonyl, the substituent R is consistent with Table 1, and represents the compound number 80.1-80.360, corresponding to Table 1 in turn 1.1-1.360.
表81：通式I-W 1-1中，当R 1＝SCH 3且R 2＝甲氧基羰基时，取代基R与表1一致，代表化合物编号为81.1-81.360，依次对应表1的1.1-1.360。 Table 81: In the general formula IW 1 -1, when R 1 =SCH 3 and R 2 =methoxycarbonyl, the substituent R is consistent with Table 1, and the representative compound number is 81.1-81.360, corresponding to 1.1- in Table 1 in turn 1.360.
表82：通式I-W 1-1中，当R 1＝SCH 2CH 3且R 2＝甲氧基羰基时，取代基R与表1一致，代表化合物编号为82.1-82.360，依次对应表1的1.1-1.360。 Table 82: In the general formula IW 1 -1, when R 1 =SCH 2 CH 3 and R 2 =methoxycarbonyl, the substituent R is consistent with Table 1, which represents compound numbers 82.1-82.360, corresponding to those in Table 1. 1.1-1.360.
表83：通式I-W 1-1中，当R 1＝NH 2且R 2＝甲氧基羰基时，取代基R与表1一致，代表化合物编号为83.1-83.360，依次对应表1的1.1-1.360。 Table 83: In the general formula IW 1 -1, when R 1 =NH 2 and R 2 =methoxycarbonyl, the substituent R is consistent with Table 1, and the representative compound number is 83.1-83.360, corresponding to 1.1- in Table 1 in turn 1.360.
表84：通式I-W 1-1中，当R 1＝NHCH 3且R 2＝甲氧基羰基时，取代基R与表1一致，代表化合物编号为84.1-84.360，依次对应表1的1.1-1.360。 Table 84: In the general formula IW 1 -1, when R 1 =NHCH 3 and R 2 =methoxycarbonyl, the substituent R is consistent with Table 1, and the representative compound number is 84.1-84.360, corresponding to 1.1- in Table 1 in turn 1.360.
表85：通式I-W 1-1中，当R 1＝NHCH 2CH 3且R 2＝甲氧基羰基时，取代基R与表1一致，代表化合物编号为85.1-85.360，依次对应表1的1.1-1.360。 Table 85: In the general formula IW 1 -1, when R 1 =NHCH 2 CH 3 and R 2 =methoxycarbonyl, the substituent R is consistent with Table 1, and represents the compound number 85.1-85.360, corresponding to Table 1 in turn 1.1-1.360.
表86：通式I-W 1-1中，当R 1＝N(CH 3) 2且R 2＝甲氧基羰基时，取代基R与表1一致，代表化合物编号为86.1-86.360，依次对应表1的1.1-1.360。 Table 86: In the general formula IW 1 -1, when R 1 =N(CH 3 ) 2 and R 2 =methoxycarbonyl, the substituent R is consistent with Table 1, representing compound numbers 86.1-86.360, corresponding to the table in turn 1 of 1.1-1.360.
表87：通式I-W 1-1中，当R 1＝OCH 3且R 2＝甲氧基羰基时，取代基R与表1一致，代表化合物编号为87.1-87.360，依次对应表1的1.1-1.360。 Table 87: In the general formula IW 1 -1, when R 1 =OCH 3 and R 2 =methoxycarbonyl, the substituent R is consistent with Table 1, and the representative compound number is 87.1-87.360, corresponding to 1.1- in Table 1 in turn 1.360.
表88：通式I-W 1-1中，当R 1＝OCH 2CH 3且R 2＝甲氧基羰基时，取代基R与表1一致，代表化合物编号为88.1-88.360，依次对应表1的1.1-1.360。 Table 88: In the general formula IW 1 -1, when R 1 =OCH 2 CH 3 and R 2 =methoxycarbonyl, the substituent R is consistent with Table 1, and represents the compound number 88.1-88.360, corresponding to Table 1 in turn 1.1-1.360.
表89：通式I-W 1-1中，当R 1＝H且R 2＝乙氧基羰基时，取代基R与表1一致，代表化合物编号为89.1-89.360，依次对应表1的1.1-1.360。 Table 89: In the general formula IW 1 -1, when R 1 =H and R 2 =ethoxycarbonyl, the substituent R is consistent with Table 1, and the representative compound number is 89.1-89.360, corresponding to 1.1-1.360 of Table 1 in turn .
表90：通式I-W 1-1中，当R 1＝CH 3且R 2＝乙氧基羰基时，取代基R与表1一致，代表化合物编号为90.1-90.360，依次对应表1的1.1-1.360。 Table 90: In the general formula IW 1 -1, when R 1 =CH 3 and R 2 =ethoxycarbonyl, the substituent R is consistent with Table 1, and the representative compound number is 90.1-90.360, corresponding to 1.1- in Table 1 in turn 1.360.
表91：通式I-W 1-1中，当R 1＝CH 2CH 3且R 2＝乙氧基羰基时，取代基R与表1一致，代表化合物编号为91.1-91.360，依次对应表1的1.1-1.360。 Table 91: In the general formula IW 1 -1, when R 1 =CH 2 CH 3 and R 2 =ethoxycarbonyl, the substituent R is consistent with Table 1, and represents compound numbers 91.1-91.360, corresponding to those in Table 1 in turn 1.1-1.360.
表92：通式I-W 1-1中，当R 1＝SCH 3且R 2＝乙氧基羰基时，取代基R与表1一致，代表化合物编号为92.1-92.360，依次对应表1的1.1-1.360。 Table 92: In the general formula IW 1 -1, when R 1 =SCH 3 and R 2 =ethoxycarbonyl, the substituent R is consistent with Table 1, and the representative compound number is 92.1-92.360, corresponding to 1.1- in Table 1 in turn 1.360.
表93：通式I-W 1-1中，当R 1＝SCH 2CH 3且R 2＝乙氧基羰基时，取代基R与表1一 致，代表化合物编号为93.1-93.360，依次对应表1的1.1-1.360。 Table 93: In the general formula IW 1 -1, when R 1 =SCH 2 CH 3 and R 2 =ethoxycarbonyl, the substituent R is consistent with Table 1, representing compound numbers 93.1-93.360, corresponding to those in Table 1 in turn 1.1-1.360.
表94：通式I-W 1-1中，当R 1＝NH 2且R 2＝乙氧基羰基时，取代基R与表1一致，代表化合物编号为94.1-94.360，依次对应表1的1.1-1.360。 Table 94: In the general formula IW 1 -1, when R 1 =NH 2 and R 2 =ethoxycarbonyl, the substituent R is consistent with Table 1, and the representative compound number is 94.1-94.360, corresponding to 1.1- in Table 1 in turn 1.360.
表95：通式I-W 1-1中，当R 1＝NHCH 3且R 2＝乙氧基羰基时，取代基R与表1一致，代表化合物编号为95.1-95.360，依次对应表1的1.1-1.360。 Table 95: In the general formula IW 1 -1, when R 1 =NHCH 3 and R 2 =ethoxycarbonyl, the substituent R is consistent with Table 1, and the representative compound number is 95.1-95.360, corresponding to 1.1- in Table 1 in turn 1.360.
表96：通式I-W 1-1中，当R 1＝NHCH 2CH 3且R 2＝乙氧基羰基时，取代基R与表1一致，代表化合物编号为96.1-96.360，依次对应表1的1.1-1.360。 Table 96: In the general formula IW 1 -1, when R 1 =NHCH 2 CH 3 and R 2 =ethoxycarbonyl, the substituent R is consistent with Table 1, representing compound numbers 96.1-96.360, corresponding to those in Table 1 in turn 1.1-1.360.
表97：通式I-W 1-1中，当R 1＝N(CH 3) 2且R 2＝乙氧基羰基时，取代基R与表1一致，代表化合物编号为97.1-97.360，依次对应表1的1.1-1.360。 Table 97: In the general formula IW 1 -1, when R 1 =N(CH 3 ) 2 and R 2 =ethoxycarbonyl, the substituent R is consistent with Table 1, which represents compound numbers 97.1-97.360, corresponding to the table in turn 1 of 1.1-1.360.
表98：通式I-W 1-1中，当R 1＝OCH 3且R 2＝乙氧基羰基时，取代基R与表1一致，代表化合物编号为98.1-98.360，依次对应表1的1.1-1.360。 Table 98: In the general formula IW 1 -1, when R 1 =OCH 3 and R 2 =ethoxycarbonyl, the substituent R is consistent with Table 1, and the representative compound number is 98.1-98.360, corresponding to 1.1- in Table 1 in turn 1.360.
表99：通式I-W 1-1中，当R 1＝OCH 2CH 3且R 2＝乙氧基羰基时，取代基R与表1一致，代表化合物编号为99.1-99.360，依次对应表1的1.1-1.360。 Table 99: In the general formula IW 1 -1, when R 1 =OCH 2 CH 3 and R 2 =ethoxycarbonyl, the substituent R is consistent with Table 1, representing compound numbers 99.1-99.360, corresponding to those in Table 1. 1.1-1.360.
通式I中，当W＝W 1且n＝0时，通式I化合物以通式I-W 1-0表示。 In the general formula I, when W=W 1 and n=0, the compound of the general formula I is represented by the general formula IW 1 -0.
Figure PCTCN2020073096-appb-000007
Figure PCTCN2020073096-appb-000007
表100：通式I-W 1-0中，当R 1＝H且R 2＝H时，取代基R与表1一致，代表化合物编号为100.1-100.360，依次对应表1的1.1-1.360。 Table 100: In the general formula IW 1 -0, when R 1 =H and R 2 =H, the substituent R is consistent with Table 1, and represents the compound number 100.1-100.360, corresponding to 1.1-1.360 in Table 1 in turn.
表101：通式I-W 1-0中，当R 1＝CH 3且R 2＝H时，取代基R与表1一致，代表化合物编号为101.1-101.360，依次对应表1的1.1-1.360。 Table 101: In the general formula IW 1 -0, when R 1 =CH 3 and R 2 =H, the substituent R is consistent with Table 1, and the representative compound number is 101.1-101.360, corresponding to 1.1-1.360 of Table 1 in turn.
表102：通式I-W 1-0中，当R 1＝CH 2CH 3且R 2＝H时，取代基R与表1一致，代表化合物编号为102.1-102.360，依次对应表1的1.1-1.360。 Table 102: In the general formula IW 1 -0, when R 1 =CH 2 CH 3 and R 2 =H, the substituent R is consistent with Table 1, and the representative compound number is 102.1-102.360, corresponding to 1.1-1.360 in Table 1 in turn .
表103：通式I-W 1-0中，当R 1＝SCH 3且R 2＝H时，取代基R与表1一致，代表化合物编号为103.1-103.360，依次对应表1的1.1-1.360。 Table 103: In the general formula IW 1 -0, when R 1 =SCH 3 and R 2 =H, the substituent R is consistent with Table 1, and the representative compound number is 103.1-103.360, corresponding to 1.1-1.360 of Table 1 in turn.
表104：通式I-W 1-0中，当R 1＝SCH 2CH 3且R 2＝H时，取代基R与表1一致，代表化合物编号为104.1-104.360，依次对应表1的1.1-1.360。 Table 104: In the general formula IW 1 -0, when R 1 =SCH 2 CH 3 and R 2 =H, the substituent R is consistent with Table 1, and the representative compound number is 104.1-104.360, corresponding to 1.1-1.360 in Table 1 in turn .
表105：通式I-W 1-0中，当R 1＝NH 2且R 2＝H时，取代基R与表1一致，代表化合物编号为105.1-105.360，依次对应表1的1.1-1.360。 Table 105: In the general formula IW 1 -0, when R 1 =NH 2 and R 2 =H, the substituent R is consistent with Table 1, and the representative compound number is 105.1-105.360, corresponding to 1.1-1.360 of Table 1 in turn.
表106：通式I-W 1-0中，当R 1＝NHCH 3且R 2＝H时，取代基R与表1一致，代表化合物编号为106.1-106.360，依次对应表1的1.1-1.360。 Table 106: In the general formula IW 1 -0, when R 1 =NHCH 3 and R 2 =H, the substituent R is consistent with Table 1, and the representative compound number is 106.1-106.360, corresponding to 1.1-1.360 of Table 1 in turn.
表107：通式I-W 1-0中，当R 1＝NHCH 2CH 3且R 2＝H时，取代基R与表1一致，代表化合物编号为107.1-107.360，依次对应表1的1.1-1.360。 Table 107: In the general formula IW 1 -0, when R 1 =NHCH 2 CH 3 and R 2 =H, the substituent R is consistent with Table 1, and the representative compound number is 107.1-107.360, corresponding to 1.1-1.360 in Table 1 in turn .
表108：通式I-W 1-0中，当R 1＝N(CH 3) 2且R 2＝H时，取代基R与表1一致，代表化合物编号为108.1-108.360，依次对应表1的1.1-1.360。 Table 108: In the general formula IW 1 -0, when R 1 ＝N(CH 3 ) 2 and R 2 ＝H, the substituent R is consistent with Table 1, representing the compound number of 108.1-108.360, corresponding to 1.1 in Table 1 in turn -1.360.
表109：通式I-W 1-0中，当R 1＝OCH 3且R 2＝H时，取代基R与表1一致，代表化合物编号为109.1-109.360，依次对应表1的1.1-1.360。 Table 109: In the general formula IW 1 -0, when R 1 =OCH 3 and R 2 =H, the substituent R is consistent with Table 1, and the representative compound number is 109.1-109.360, corresponding to 1.1-1.360 of Table 1 in turn.
表110：通式I-W 1-0中，当R 1＝OCH 2CH 3且R 2＝H时，取代基R与表1一致，代表化合物编号为110.1-110.360，依次对应表1的1.1-1.360。 Table 110: In the general formula IW 1 -0, when R 1 ＝OCH 2 CH 3 and R 2 ＝H, the substituent R is consistent with Table 1, and the representative compound number is 110.1-110.360, corresponding to 1.1-1.360 of Table 1 in turn .
表111：通式I-W 1-0中，当R 1＝H且R 2＝CH 3时，取代基R与表1一致，代表化合物编号为111.1-111.360，依次对应表1的1.1-1.360。 Table 111: In the general formula IW 1 -0, when R 1 =H and R 2 =CH 3 , the substituent R is consistent with Table 1, and the representative compound number is 111.1-111.360, corresponding to 1.1-1.360 in Table 1 in turn.
表112：通式I-W 1-0中，当R 1＝CH 3且R 2＝CH 3时，取代基R与表1一致，代表化 合物编号为112.1-112.360，依次对应表1的1.1-1.360。 Table 112: Formula IW 1 -0, where R 1 = CH 3 and R 2 = CH 3, the substituents R are consistent with Table 1, the representative compounds are numbered 112.1-112.360, Table 1 in turn corresponds to the 1.1-1.360.
表113：通式I-W 1-0中，当R 1＝CH 2CH 3且R 2＝CH 3时，取代基R与表1一致，代表化合物编号为113.1-113.360，依次对应表1的1.1-1.360。 Table 113: In the general formula IW 1 -0, when R 1 =CH 2 CH 3 and R 2 =CH 3 , the substituent R is consistent with Table 1, which represents the compound number 113.1-113.360, corresponding to 1.1- in Table 1 1.360.
表114：通式I-W 1-0中，当R 1＝SCH 3且R 2＝CH 3时，取代基R与表1一致，代表化合物编号为114.1-114.360，依次对应表1的1.1-1.360。 Table 114: In the general formula IW 1 -0, when R 1 =SCH 3 and R 2 =CH 3 , the substituent R is consistent with Table 1, and the representative compound number is 114.1-114.360, corresponding to 1.1-1.360 of Table 1 in turn.
表115：通式I-W 1-0中，当R 1＝SCH 2CH 3且R 2＝CH 3时，取代基R与表1一致，代表化合物编号为115.1-115.360，依次对应表1的1.1-1.360。 Table 115: In the general formula IW 1 -0, when R 1 =SCH 2 CH 3 and R 2 =CH 3 , the substituent R is consistent with Table 1, and the representative compound number is 115.1-115.360, corresponding to 1.1- in Table 1 in turn 1.360.
表116：通式I-W 1-0中，当R 1＝NH 2且R 2＝CH 3时，取代基R与表1一致，代表化合物编号为116.1-116.360，依次对应表1的1.1-1.360。 Table 116: In the general formula IW 1 -0, when R 1 =NH 2 and R 2 =CH 3 , the substituent R is consistent with Table 1, and the representative compound number is 116.1-116.360, corresponding to 1.1-1.360 of Table 1 in turn.
表117：通式I-W 1-0中，当R 1＝NHCH 3且R 2＝CH 3时，取代基R与表1一致，代表化合物编号为117.1-117.360，依次对应表1的1.1-1.360。 Table 117: Formula IW 1 -0, where R 1 = NHCH 3 and R 2 = CH 3, the substituent R is consistent with Table 1, the representative compounds are numbered 117.1-117.360, Table 1 in turn corresponds to the 1.1-1.360.
表118：通式I-W 1-0中，当R 1＝NHCH 2CH 3且R 2＝CH 3时，取代基R与表1一致，代表化合物编号为118.1-118.360，依次对应表1的1.1-1.360。 Table 118: In the general formula IW 1 -0, when R 1 =NHCH 2 CH 3 and R 2 =CH 3 , the substituent R is consistent with Table 1, which represents compound numbers 118.1-118.360, corresponding to 1.1- in Table 1 in turn 1.360.
表119：通式I-W 1-0中，当R 1＝N(CH 3) 2且R 2＝CH 3时，取代基R与表1一致，代表化合物编号为119-119.360，依次对应表1的1.1-1.360。 Table 119: In the general formula IW 1 -0, when R 1 ＝N(CH 3 ) 2 and R 2 ＝CH 3 , the substituent R is consistent with Table 1, and represents the compound number 119-119.360, which corresponds to Table 1 in turn 1.1-1.360.
表120：通式I-W 1-0中，当R 1＝OCH 3且R 2＝CH 3时，取代基R与表1一致，代表化合物编号为120.1-120.360，依次对应表1的1.1-1.360。 Table 120: In the general formula IW 1 -0, when R 1 ═OCH 3 and R 2 ═CH 3 , the substituent R is consistent with Table 1, and the representative compound number is 120.1-120.360, corresponding to 1.1-1.360 of Table 1 in turn.
表121：通式I-W 1-0中，当R 1＝OCH 2CH 3且R 2＝CH 3时，取代基R与表1一致，代表化合物编号为121.1-121.360，依次对应表1的1.1-1.360。 Table 121: In the general formula IW 1 -0, when R 1 ＝OCH 2 CH 3 and R 2 ＝CH 3 , the substituent R is consistent with Table 1, and the representative compound number is 121.1-121.360, corresponding to 1.1- in Table 1 in turn 1.360.
表122：通式I-W 1-0中，当R 1＝H且R 2＝CH 2CH 3时，取代基R与表1一致，代表化合物编号为122.1-122.360，依次对应表1的1.1-1.360。 Table 122: In the general formula IW 1 -0, when R 1 =H and R 2 =CH 2 CH 3 , the substituent R is consistent with Table 1, and the representative compound number is 122.1-122.360, corresponding to 1.1-1.360 in Table 1 in turn .
表123：通式I-W 1-0中，当R 1＝CH 3且R 2＝CH 2CH 3时，取代基R与表1一致，代表化合物编号为123.1-123.360，依次对应表1的1.1-1.360。 Table 123: In the general formula IW 1 -0, when R 1 =CH 3 and R 2 =CH 2 CH 3 , the substituent R is consistent with Table 1, which represents the compound number 123.1-123.360, corresponding to 1.1- in Table 1 1.360.
表124：通式I-W 1-0中，当R 1＝CH 2CH 3且R 2＝CH 2CH 3时，取代基R与表1一致，代表化合物编号为124.1-124.360，依次对应表1的1.1-1.360。 Table 124: In the general formula IW 1 -0, when R 1 =CH 2 CH 3 and R 2 =CH 2 CH 3 , the substituent R is consistent with Table 1, which represents compound numbers 124.1-124.360, corresponding to those in Table 1 in turn 1.1-1.360.
表125：通式I-W 1-0中，当R 1＝SCH 3且R 2＝CH 2CH 3时，取代基R与表1一致，代表化合物编号为125.1-125.360，依次对应表1的1.1-1.360。 Table 125: In the general formula IW 1 -0, when R 1 =SCH 3 and R 2 =CH 2 CH 3 , the substituent R is consistent with Table 1, and the representative compound number is 125.1-125.360, corresponding to 1.1- in Table 1 in turn 1.360.
表126：通式I-W 1-0中，当R 1＝SCH 2CH 3且R 2＝CH 2CH 3时，取代基R与表1一致，代表化合物编号为126.1-126.360，依次对应表1的1.1-1.360。 Table 126: In the general formula IW 1 -0, when R 1 =SCH 2 CH 3 and R 2 =CH 2 CH 3 , the substituent R is consistent with Table 1, which represents compound numbers 126.1-126.360, corresponding to those in Table 1. 1.1-1.360.
表127：通式I-W 1-0中，当R 1＝NH 2且R 2＝CH 2CH 3时，取代基R与表1一致，代表化合物编号为127.1-127.360，依次对应表1的1.1-1.360。 Table 127: In the general formula IW 1 -0, when R 1 =NH 2 and R 2 =CH 2 CH 3 , the substituent R is consistent with Table 1, and the representative compound number is 127.1-127.360, corresponding to 1.1- in Table 1 in turn 1.360.
表128：通式I-W 1-0中，当R 1＝NHCH 3且R 2＝CH 2CH 3时，取代基R与表1一致，代表化合物编号为128.1-128.360，依次对应表1的1.1-1.360。 Table 128: In the general formula IW 1 -0, when R 1 ＝NHCH 3 and R 2 ＝CH 2 CH 3 , the substituent R is consistent with Table 1, and the representative compound number is 128.1-128.360, corresponding to 1.1- of Table 1 in turn 1.360.
表129：通式I-W 1-0中，当R 1＝NHCH 2CH 3且R 2＝CH 2CH 3时，取代基R与表1一致，代表化合物编号为129.1-129.360，依次对应表1的1.1-1.360。 Table 129: In the general formula IW 1 -0, when R 1 =NHCH 2 CH 3 and R 2 =CH 2 CH 3 , the substituent R is consistent with Table 1, representing the compound numbers 129.1-129.360, corresponding to those in Table 1 in turn 1.1-1.360.
表130：通式I-W 1-0中，当R 1＝N(CH 3) 2且R 2＝CH 2CH 3时，取代基R与表1一致，代表化合物编号为130.1-130.360，依次对应表1的1.1-1.360。 Table 130: In the general formula IW 1 -0, when R 1 ＝N(CH 3 ) 2 and R 2 ＝CH 2 CH 3 , the substituent R is consistent with Table 1, which represents compound numbers 130.1-130.360, corresponding to the table in turn 1 of 1.1-1.360.
表131：通式I-W 1-0中，当R 1＝OCH 3且R 2＝CH 2CH 3时，取代基R与表1一致，代表化合物编号为131.1-131.360，依次对应表1的1.1-1.360。 Table 131: In the general formula IW 1 -0, when R 1 ＝OCH 3 and R 2 ＝CH 2 CH 3 , the substituent R is consistent with Table 1, and the representative compound number is 131.1-131.360, corresponding to 1.1- in Table 1 in turn 1.360.
表132：通式I-W 1-0中，当R 1＝OCH 2CH 3且R 2＝CH 2CH 3时，取代基R与表1一致，代表化合物编号为132.1-132.360，依次对应表1的1.1-1.360。 Table 132: In the general formula IW 1 -0, when R 1 ＝OCH 2 CH 3 and R 2 ＝CH 2 CH 3 , the substituent R is consistent with Table 1, which represents compound numbers 132.1-132.360, corresponding to those in Table 1. 1.1-1.360.
表133：通式I-W 1-0中，当R 1＝H且R 2＝CH 2CN时，取代基R与表1一致，代表化合物编号为133.1-133.360，依次对应表1的1.1-1.360。 Table 133: In the general formula IW 1 -0, when R 1 =H and R 2 =CH 2 CN, the substituent R is consistent with Table 1, and the representative compound number is 133.1-133.360, corresponding to 1.1-1.360 of Table 1 in turn.
表134：通式I-W 1-0中，当R 1＝CH 3且R 2＝CH 2CN时，取代基R与表1一致，代 表化合物编号为134.1-134.360，依次对应表1的1.1-1.360。 Table 134: In the general formula IW 1 -0, when R 1 =CH 3 and R 2 =CH 2 CN, the substituent R is consistent with Table 1, and the representative compound number is 134.1-134.360, corresponding to 1.1-1.360 in Table 1 in turn .
表135：通式I-W 1-0中，当R 1＝CH 2CH 3且R 2＝CH 2CN时，取代基R与表1一致，代表化合物编号为135.1-135.360，依次对应表1的1.1-1.360。 Table 135: In the general formula IW 1 -0, when R 1 =CH 2 CH 3 and R 2 =CH 2 CN, the substituent R is consistent with Table 1, which represents the compound number 135.1-135.360, corresponding to 1.1 in Table 1 in turn -1.360.
表136：通式I-W 1-0中，当R 1＝SCH 3且R 2＝CH 2CN时，取代基R与表1一致，代表化合物编号为136.1-136.360，依次对应表1的1.1-1.360。 Table 136: In the general formula IW 1 -0, when R 1 =SCH 3 and R 2 =CH 2 CN, the substituent R is consistent with Table 1, and the representative compound number is 136.1-136.360, corresponding to 1.1-1.360 in Table 1 in turn .
表137：通式I-W 1-0中，当R 1＝SCH 2CH 3且R 2＝CH 2CN时，取代基R与表1一致，代表化合物编号为137.1-137.360，依次对应表1的1.1-1.360。 Table 137: In the general formula IW 1 -0, when R 1 =SCH 2 CH 3 and R 2 =CH 2 CN, the substituent R is consistent with Table 1, which represents compound numbers 137.1-137.360, corresponding to 1.1 in Table 1 in turn -1.360.
表138：通式I-W 1-0中，当R 1＝NH 2且R 2＝CH 2CN时，取代基R与表1一致，代表化合物编号为138.1-138.360，依次对应表1的1.1-1.360。 Table 138: In the general formula IW 1 -0, when R 1 =NH 2 and R 2 =CH 2 CN, the substituent R is consistent with Table 1, and the representative compound number is 138.1-138.360, corresponding to 1.1-1.360 in Table 1 in turn .
表139：通式I-W 1-0中，当R 1＝NHCH 3且R 2＝CH 2CN时，取代基R与表1一致，代表化合物编号为139.1-139.360，依次对应表1的1.1-1.360。 Table 139: In the general formula IW 1 -0, when R 1 =NHCH 3 and R 2 =CH 2 CN, the substituent R is consistent with Table 1, and the representative compound number is 139.1-139.360, corresponding to 1.1-1.360 in Table 1 in turn .
表140：通式I-W 1-0中，当R 1＝NHCH 2CH 3且R 2＝CH 2CN时，取代基R与表1一致，代表化合物编号为140.1-140.360，依次对应表1的1.1-1.360。 Table 140: In the general formula IW 1 -0, when R 1 =NHCH 2 CH 3 and R 2 =CH 2 CN, the substituent R is consistent with Table 1, which represents the compound number 140.1-140.360, corresponding to 1.1 in Table 1 in turn -1.360.
表141：通式I-W 1-0中，当R 1＝N(CH 3) 2且R 2＝CH 2CN时，取代基R与表1一致，代表化合物编号为141.1-141.360，依次对应表1的1.1-1.360。 Table 141: In the general formula IW 1 -0, when R 1 ＝N(CH 3 ) 2 and R 2 ＝CH 2 CN, the substituent R is consistent with Table 1, which represents compound numbers 141.1-141.360, corresponding to Table 1 in turn 1.1-1.360.
表142：通式I-W 1-0中，当R 1＝OCH 3且R 2＝CH 2CN时，取代基R与表1一致，代表化合物编号为142.1-142.360，依次对应表1的1.1-1.360。 Table 142: In the general formula IW 1 -0, when R 1 ═OCH 3 and R 2 ═CH 2 CN, the substituent R is consistent with Table 1, and the representative compound number is 142.1-142.360, corresponding to 1.1-1.360 in Table 1 in turn .
表143：通式I-W 1-0中，当R 1＝OCH 2CH 3且R 2＝CH 2CN时，取代基R与表1一致，代表化合物编号为143.1-143.360，依次对应表1的1.1-1.360。 Table 143: In the general formula IW 1 -0, when R 1 ＝OCH 2 CH 3 and R 2 ＝CH 2 CN, the substituent R is consistent with Table 1, which represents the compound number 143.1-143.360, corresponding to 1.1 in Table 1 in turn -1.360.
表144：通式I-W 1-0中，当R 1＝H且R 2＝乙酰基时，取代基R与表1一致，代表化合物编号为144.1-144.360，依次对应表1的1.1-1.360。 Table 144: In the general formula IW 1 -0, when R 1 =H and R 2 =acetyl, the substituent R is consistent with Table 1, and the representative compound number is 144.1-144.360, corresponding to 1.1-1.360 of Table 1 in turn.
表145：通式I-W 1-0中，当R 1＝CH 3且R 2＝乙酰基时，取代基R与表1一致，代表化合物编号为145.1-145.360，依次对应表1的1.1-1.360。 Table 145: Formula IW 1 -0, when R 1 = CH 3 and R 2 = acetyl group, substituent group R is consistent with Table 1, the representative compounds are numbered 145.1-145.360, Table 1 in turn corresponds to the 1.1-1.360.
表146：通式I-W 1-0中，当R 1＝CH 2CH 3且R 2＝乙酰基时，取代基R与表1一致，代表化合物编号为146.1-146.360，依次对应表1的1.1-1.360。 Table 146: In the general formula IW 1 -0, when R 1 =CH 2 CH 3 and R 2 =acetyl, the substituent R is consistent with Table 1, and the representative compound number is 146.1-146.360, corresponding to 1.1- in Table 1 in turn 1.360.
表147：通式I-W 1-0中，当R 1＝SCH 3且R 2＝乙酰基时，取代基R与表1一致，代表化合物编号为147.1-147.360，依次对应表1的1.1-1.360。 Table 147: In the general formula IW 1 -0, when R 1 =SCH 3 and R 2 =acetyl, the substituent R is consistent with Table 1, and the representative compound number is 147.1-147.360, corresponding to 1.1-1.360 of Table 1 in turn.
表148：通式I-W 1-0中，当R 1＝SCH 2CH 3且R 2＝乙酰基时，取代基R与表1一致，代表化合物编号为148.1-148.360，依次对应表1的1.1-1.360。 Table 148: In the general formula IW 1 -0, when R 1 =SCH 2 CH 3 and R 2 =acetyl, the substituent R is consistent with Table 1, and the representative compound number is 148.1-148.360, corresponding to 1.1- in Table 1 in turn 1.360.
表149：通式I-W 1-0中，当R 1＝NH 2且R 2＝乙酰基时，取代基R与表1一致，代表化合物编号为149.1-149.360，依次对应表1的1.1-1.360。 Table 149: Formula IW 1 -0, when R 1 = NH 2 and R 2 = acetyl group, substituent group R is consistent with Table 1, the representative compounds are numbered 149.1-149.360, Table 1 in turn corresponds to the 1.1-1.360.
表150：通式I-W 1-0中，当R 1＝NHCH 3且R 2＝乙酰基时，取代基R与表1一致，代表化合物编号为150.1-150.360，依次对应表1的1.1-1.360。 Table 150: In the general formula IW 1 -0, when R 1 =NHCH 3 and R 2 =acetyl, the substituent R is consistent with Table 1, and the representative compound number is 150.1-150.360, corresponding to 1.1-1.360 in Table 1 in turn.
表151：通式I-W 1-0中，当R 1＝NHCH 2CH 3且R 2＝乙酰基时，取代基R与表1一致，代表化合物编号为151.1-151.360，依次对应表1的1.1-1.360。 Table 151: In the general formula IW 1 -0, when R 1 =NHCH 2 CH 3 and R 2 =acetyl, the substituent R is consistent with Table 1, and the representative compound number is 151.1-151.360, corresponding to 1.1- in Table 1 in turn 1.360.
表152：通式I-W 1-0中，当R 1＝N(CH 3) 2且R 2＝乙酰基时，取代基R与表1一致，代表化合物编号为152.1-152.360，依次对应表1的1.1-1.360。 Table 152: In the general formula IW 1 -0, when R 1 =N(CH 3 ) 2 and R 2 =acetyl, the substituent R is consistent with Table 1, and represents the compound number 152.1-152.360, corresponding to Table 1 in turn 1.1-1.360.
表153：通式I-W 1-0中，当R 1＝OCH 3且R 2＝乙酰基时，取代基R与表1一致，代表化合物编号为153.1-153.360，依次对应表1的1.1-1.360。 Table 153: In the general formula IW 1 -0, when R 1 =OCH 3 and R 2 =acetyl, the substituent R is consistent with Table 1, and the representative compound number is 153.1-153.360, corresponding to 1.1-1.360 of Table 1 in turn.
表154：通式I-W 1-0中，当R 1＝OCH 2CH 3且R 2＝乙酰基时，取代基R与表1一致，代表化合物编号为154.1-154.360，依次对应表1的1.1-1.360。 Table 154: In the general formula IW 1 -0, when R 1 =OCH 2 CH 3 and R 2 =acetyl, the substituent R is consistent with Table 1, and the representative compound number is 154.1-154.360, corresponding to 1.1- in Table 1 in turn 1.360.
表155：通式I-W 1-0中，当R 1＝H且R 2＝正丙酰基时，取代基R与表1一致，代表化合物编号为155.1-155.360，依次对应表1的1.1-1.360。 Table 155: In the general formula IW 1 -0, when R 1 =H and R 2 =n-propionyl, the substituent R is consistent with Table 1, and the representative compound number is 155.1-155.360, corresponding to 1.1-1.360 of Table 1 in turn.
表156：通式I-W 1-0中，当R 1＝CH 3且R 2＝正丙酰基时，取代基R与表1一致，代 表化合物编号为156.1-156.360，依次对应表1的1.1-1.360。 Table 156: In the general formula IW 1 -0, when R 1 =CH 3 and R 2 =n-propionyl, the substituent R is consistent with Table 1, and the representative compound number is 156.1-156.360, corresponding to 1.1-1.360 in Table 1 in turn .
表157：通式I-W 1-0中，当R 1＝CH 2CH 3且R 2＝正丙酰基时，取代基R与表1一致，代表化合物编号为157.1-157.360，依次对应表1的1.1-1.360。 Table 157: In the general formula IW 1 -0, when R 1 =CH 2 CH 3 and R 2 =n-propionyl, the substituent R is consistent with Table 1, and the representative compound number is 157.1-157.360, corresponding to 1.1 in Table 1 in turn -1.360.
表158：通式I-W 1-0中，当R 1＝SCH 3且R 2＝正丙酰基时，取代基R与表1一致，代表化合物编号为158.1-158.360，依次对应表1的1.1-1.360。 Table 158: In the general formula IW 1 -0, when R 1 =SCH 3 and R 2 =n-propionyl, the substituent R is consistent with Table 1, and the representative compound number is 158.1-158.360, corresponding to 1.1-1.360 in Table 1 in turn .
表159：通式I-W 1-0中，当R 1＝SCH 2CH 3且R 2＝正丙酰基时，取代基R与表1一致，代表化合物编号为159.1-159.360，依次对应表1的1.1-1.360。 Table 159: In the general formula IW 1 -0, when R 1 =SCH 2 CH 3 and R 2 =n-propionyl, the substituent R is consistent with Table 1, and the representative compound number is 159.1-159.360, corresponding to 1.1 in Table 1 in turn -1.360.
表160：通式I-W 1-0中，当R 1＝NH 2且R 2＝正丙酰基时，取代基R与表1一致，代表化合物编号为160.1-160.360，依次对应表1的1.1-1.360。 Table 160: In the general formula IW 1 -0, when R 1 =NH 2 and R 2 = n-propionyl, the substituent R is consistent with Table 1, and the representative compound number is 160.1-160.360, corresponding to 1.1-1.360 in Table 1 in turn .
表161：通式I-W 1-0中，当R 1＝NHCH 3且R 2＝正丙酰基时，取代基R与表1一致，代表化合物编号为161.1-161.360，依次对应表1的1.1-1.360。 Table 161: In the general formula IW 1 -0, when R 1 =NHCH 3 and R 2 =n-propionyl, the substituent R is consistent with Table 1, and the representative compound number is 161.1-161.360, corresponding to 1.1-1.360 in Table 1 in turn .
表162：通式I-W1-0中，当R 1＝NHCH 2CH 3且R 2＝正丙酰基时，取代基R与表1一致，代表化合物编号为162.1-162.360，依次对应表1的1.1-1.360。 Table 162: In the general formula I-W1-0, when R 1 =NHCH 2 CH 3 and R 2 = n-propionyl, the substituent R is consistent with Table 1, which represents compound numbers 162.1-162.360, corresponding to those in Table 1. 1.1-1.360.
表163：通式I-W 1-0中，当R 1＝N(CH 3) 2且R 2＝正丙酰基时，取代基R与表1一致，代表化合物编号为163.1-163.360，依次对应表1的1.1-1.360。 Table 163: In the general formula IW 1 -0, when R 1 =N(CH 3 ) 2 and R 2 =n-propionyl, the substituent R is consistent with Table 1, representing compound numbers 163.1-163.360, corresponding to Table 1 in turn 1.1-1.360.
表164：通式I-W 1-0中，当R 1＝OCH 3且R 2＝正丙酰基时，取代基R与表1一致，代表化合物编号为164.1-164.360，依次对应表1的1.1-1.360。 Table 164: In the general formula IW 1 -0, when R 1 =OCH 3 and R 2 =n-propionyl, the substituent R is consistent with Table 1, and the representative compound number is 164.1-164.360, corresponding to 1.1-1.360 in Table 1 in turn .
表165：通式I-W 1-0中，当R 1＝OCH 2CH 3且R 2＝正丙酰基时，取代基R与表1一致，代表化合物编号为165.1-165.360，依次对应表1的1.1-1.360。 Table 165: In the general formula IW 1 -0, when R 1 =OCH 2 CH 3 and R 2 =n-propionyl, the substituent R is consistent with Table 1, which represents compound numbers 165.1-165.360, corresponding to 1.1 in Table 1 in turn -1.360.
表166：通式I-W 1-0中，当R 1＝H且R 2＝环丙基甲酰基时，取代基R与表1一致，代表化合物编号为166.1-166.360，依次对应表1的1.1-1.360。 Table 166: In the general formula IW 1 -0, when R 1 =H and R 2 =cyclopropylformyl, the substituent R is consistent with Table 1, and the representative compound number is 166.1-166.360, corresponding to 1.1- in Table 1 in turn 1.360.
表167：通式I-W 1-0中，当R 1＝CH 3且R 2＝环丙基甲酰基时，取代基R与表1一致，代表化合物编号为167.1-167.360，依次对应表1的1.1-1.360。 Table 167: In the general formula IW 1 -0, when R 1 =CH 3 and R 2 =cyclopropylformyl, the substituent R is consistent with Table 1, which represents compound numbers 167.1-167.360, corresponding to 1.1 in Table 1 in turn -1.360.
表168：通式I-W 1-0中，当R 1＝CH 2CH 3且R 2＝环丙基甲酰基时，取代基R与表1一致，代表化合物编号为168.1-168.360，依次对应表1的1.1-1.360。 Table 168: In the general formula IW 1 -0, when R 1 =CH 2 CH 3 and R 2 =cyclopropylformyl, the substituent R is consistent with Table 1, representing the compound number of 168.1–168.360, corresponding to Table 1 in turn 1.1-1.360.
表169：通式I-W 1-0中，当R 1＝SCH 3且R 2＝环丙基甲酰基时，取代基R与表1一致，代表化合物编号为169.1-169.360，依次对应表1的1.1-1.360。 Table 169: In the general formula IW 1 -0, when R 1 =SCH 3 and R 2 =cyclopropylformyl, the substituent R is consistent with Table 1, and the representative compound number is 169.1-169.360, corresponding to 1.1 in Table 1 in turn -1.360.
表170：通式I-W 1-0中，当R 1＝SCH 2CH 3且R 2＝环丙基甲酰基时，取代基R与表1一致，代表化合物编号为170.1-170.360，依次对应表1的1.1-1.360。 Table 170: In the general formula IW 1 -0, when R 1 =SCH 2 CH 3 and R 2 =cyclopropylformyl, the substituent R is consistent with Table 1, representing compound numbers 170.1-170.360, corresponding to Table 1 in turn 1.1-1.360.
表171：通式I-W 1-0中，当R 1＝NH 2且R 2＝环丙基甲酰基时，取代基R与表1一致，代表化合物编号为171.1-171.360，依次对应表1的1.1-1.360。 Table 171: In the general formula IW 1 -0, when R 1 =NH 2 and R 2 =cyclopropylformyl, the substituent R is consistent with Table 1, and the representative compound number is 171.1-171.360, corresponding to 1.1 in Table 1 in turn -1.360.
表172：通式I-W 1-0中，当R 1＝NHCH 3且R 2＝环丙基甲酰基时，取代基R与表1一致，代表化合物编号为172.1-172.360，依次对应表1的1.1-1.360。 Table 172: In the general formula IW 1 -0, when R 1 =NHCH 3 and R 2 =cyclopropylformyl, the substituent R is consistent with Table 1, representing compound numbers 172.1-172.360, corresponding to 1.1 in Table 1 in turn -1.360.
表173：通式I-W 1-0中，当R 1＝NHCH 2CH 3且R 2＝环丙基甲酰基时，取代基R与表1一致，代表化合物编号为173.1-173.360，依次对应表1的1.1-1.360。 Table 173: In the general formula IW 1 -0, when R 1 =NHCH 2 CH 3 and R 2 =cyclopropylformyl, the substituent R is consistent with Table 1, representing compound numbers 173.1-173.360, corresponding to Table 1 in turn 1.1-1.360.
表174：通式I-W 1-0中，当R 1＝N(CH 3) 2且R 2＝环丙基甲酰基时，取代基R与表1一致，代表化合物编号为174.1-174.360，依次对应表1的1.1-1.360。 Table 174: In the general formula IW 1 -0, when R 1 =N(CH 3 ) 2 and R 2 =cyclopropylformyl, the substituent R is consistent with Table 1, which represents compound numbers 174.1-174.360, corresponding in turn Table 1. 1.1-1.360.
表175：通式I-W 1-0中，当R 1＝OCH 3且R 2＝环丙基甲酰基时，取代基R与表1一致，代表化合物编号为175.1-175.360，依次对应表1的1.1-1.360。 Table 175: In the general formula IW 1 -0, when R 1 =OCH 3 and R 2 =cyclopropylformyl, the substituent R is consistent with Table 1, which represents compound numbers 175.1-175.360, corresponding to 1.1 in Table 1 in turn -1.360.
表176：通式I-W 1-0中，当R 1＝OCH 2CH 3且R 2＝环丙基甲酰基时，取代基R与表1一致，代表化合物编号为176.1-176.360，依次对应表1的1.1-1.360。 Table 176: In the general formula IW 1 -0, when R 1 =OCH 2 CH 3 and R 2 =cyclopropylformyl, the substituent R is consistent with Table 1, representing compound numbers 176.1-176.360, corresponding to Table 1 in turn 1.1-1.360.
表177：通式I-W 1-0中，当R 1＝H且R 2＝甲氧基羰基时，取代基R与表1一致，代表化合物编号为177.1-177.360，依次对应表1的1.1-1.360。 Table 177: In the general formula IW 1 -0, when R 1 =H and R 2 =methoxycarbonyl, the substituent R is consistent with Table 1, and the representative compound number is 177.1-177.360, corresponding to 1.1-1.360 in Table 1 in turn .
表178：通式I-W 1-0中，当R 1＝CH 3且R 2＝甲氧基羰基时，取代基R与表1一致， 代表化合物编号为178.1-178.360，依次对应表1的1.1-1.360。 Table 178: In the general formula IW 1 -0, when R 1 =CH 3 and R 2 =methoxycarbonyl, the substituent R is consistent with Table 1, and the representative compound number is 178.1-178.360, corresponding to 1.1- in Table 1 in turn 1.360.
表179：通式I-W 1-0中，当R 1＝CH 2CH 3且R 2＝甲氧基羰基时，取代基R与表1一致，代表化合物编号为179.1-179.360，依次对应表1的1.1-1.360。 Table 179: In the general formula IW 1 -0, when R 1 =CH 2 CH 3 and R 2 =methoxycarbonyl, the substituent R is consistent with Table 1, which represents compound numbers 179.1-179.360, corresponding to those in Table 1 in turn 1.1-1.360.
表180：通式I-W 1-0中，当R 1＝SCH 3且R 2＝甲氧基羰基时，取代基R与表1一致，代表化合物编号为180.1-180.360，依次对应表1的1.1-1.360。 Table 180: In the general formula IW 1 -0, when R 1 =SCH 3 and R 2 =methoxycarbonyl, the substituent R is consistent with Table 1, and the representative compound number is 180.1-180.360, corresponding to 1.1- in Table 1 in turn 1.360.
表181：通式I-W 1-0中，当R 1＝SCH 2CH 3且R 2＝甲氧基羰基时，取代基R与表1一致，代表化合物编号为181.1-181.360，依次对应表1的1.1-1.360。 Table 181: In the general formula IW 1 -0, when R 1 =SCH 2 CH 3 and R 2 =methoxycarbonyl, the substituent R is consistent with Table 1, which represents compound numbers 181.1-181.360, corresponding to those in Table 1. 1.1-1.360.
表182：通式I-W 1-0中，当R 1＝NH 2且R 2＝甲氧基羰基时，取代基R与表1一致，代表化合物编号为182.1-182.360，依次对应表1的1.1-1.360。 Table 182: In the general formula IW 1 -0, when R 1 =NH 2 and R 2 =methoxycarbonyl, the substituent R is consistent with Table 1, and the representative compound number is 182.1-182.360, corresponding to 1.1- in Table 1 in turn 1.360.
表183：通式I-W 1-0中，当R 1＝NHCH 3且R 2＝甲氧基羰基时，取代基R与表1一致，代表化合物编号为183.1-183.360，依次对应表1的1.1-1.360。 Table 183: In the general formula IW 1 -0, when R 1 =NHCH 3 and R 2 =methoxycarbonyl, the substituent R is consistent with Table 1, and the representative compound number is 183.1-183.360, corresponding to 1.1- in Table 1 in turn 1.360.
表184：通式I-W 1-0中，当R 1＝NHCH 2CH 3且R 2＝甲氧基羰基时，取代基R与表1一致，代表化合物编号为184.1-184.360，依次对应表1的1.1-1.360。 Table 184: In the general formula IW 1 -0, when R 1 =NHCH 2 CH 3 and R 2 =methoxycarbonyl, the substituent R is consistent with Table 1, which represents compound numbers 184.1-184.360, corresponding to Table 1 in turn 1.1-1.360.
表185：通式I-W 1-0中，当R 1＝N(CH 3) 2且R 2＝甲氧基羰基时，取代基R与表1一致，代表化合物编号为185.1-185.360，依次对应表1的1.1-1.360。 Table 185: In the general formula IW 1 -0, when R 1 =N(CH 3 ) 2 and R 2 =methoxycarbonyl, the substituent R is consistent with Table 1, representing compound numbers 185.1-185.360, corresponding to the table in turn 1 of 1.1-1.360.
表186：通式I-W 1-0中，当R 1＝OCH 3且R 2＝甲氧基羰基时，取代基R与表1一致，代表化合物编号为186.1-186.360，依次对应表1的1.1-1.360。 Table 186: In the general formula IW 1 -0, when R 1 =OCH 3 and R 2 =methoxycarbonyl, the substituent R is consistent with Table 1, and the representative compound number is 186.1-186.360, corresponding to 1.1- in Table 1 in turn 1.360.
表187：通式I-W 1-0中，当R 1＝OCH 2CH 3且R 2＝甲氧基羰基时，取代基R与表1一致，代表化合物编号为187.1-187.360，依次对应表1的1.1-1.360。 Table 187: In the general formula IW 1 -0, when R 1 =OCH 2 CH 3 and R 2 =methoxycarbonyl, the substituent R is consistent with Table 1, and represents the compound number 187.1-187.360, corresponding to Table 1 in turn 1.1-1.360.
表188：通式I-W 1-0中，当R 1＝H且R 2＝乙氧基羰基时，取代基R与表1一致，代表化合物编号为188.1-188.360，依次对应表1的1.1-1.360。 Table 188: In the general formula IW 1 -0, when R 1 =H and R 2 =ethoxycarbonyl, the substituent R is consistent with Table 1, and the representative compound number is 188.1-188.360, corresponding to 1.1-1.360 in Table 1 in turn .
表189：通式I-W 1-0中，当R 1＝CH 3且R 2＝乙氧基羰基时，取代基R与表1一致，代表化合物编号为189.1-189.360，依次对应表1的1.1-1.360。 Table 189: In the general formula IW 1 -0, when R 1 =CH 3 and R 2 =ethoxycarbonyl, the substituent R is consistent with Table 1, and the representative compound number is 189.1-189.360, corresponding to 1.1- in Table 1 in turn 1.360.
表190：通式I-W 1-0中，当R 1＝CH 2CH 3且R 2＝乙氧基羰基时，取代基R与表1一致，代表化合物编号为190.1-190.360，依次对应表1的1.1-1.360。 Table 190: In the general formula IW 1 -0, when R 1 =CH 2 CH 3 and R 2 =ethoxycarbonyl, the substituent R is consistent with Table 1, which represents compound numbers 190.1-190.360, corresponding to those in Table 1 in turn 1.1-1.360.
表191：通式I-W 1-0中，当R 1＝SCH 3且R 2＝乙氧基羰基时，取代基R与表1一致，代表化合物编号为191.1-191.360，依次对应表1的1.1-1.360。 Table 191: In the general formula IW 1 -0, when R 1 =SCH 3 and R 2 =ethoxycarbonyl, the substituent R is consistent with Table 1, and the representative compound number is 191.1-191.360, corresponding to 1.1- in Table 1 in turn 1.360.
表192：通式I-W 1-0中，当R 1＝SCH 2CH 3且R 2＝乙氧基羰基时，取代基R与表1一致，代表化合物编号为192.1-192.360，依次对应表1的1.1-1.360。 Table 192: In the general formula IW 1 -0, when R 1 =SCH 2 CH 3 and R 2 =ethoxycarbonyl, the substituent R is consistent with Table 1, which represents compound numbers 192.1-192.360, corresponding to those in Table 1. 1.1-1.360.
表193：通式I-W 1-0中，当R 1＝NH 2且R 2＝乙氧基羰基时，取代基R与表1一致，代表化合物编号为193.1-193.360，依次对应表1的1.1-1.360。 Table 193: In the general formula IW 1 -0, when R 1 =NH 2 and R 2 =ethoxycarbonyl, the substituent R is consistent with Table 1, and the representative compound number is 193.1-193.360, corresponding to 1.1- in Table 1 in turn 1.360.
表194：通式I-W 1-0中，当R 1＝NHCH 3且R 2＝乙氧基羰基时，取代基R与表1一致，代表化合物编号为194.1-194.360，依次对应表1的1.1-1.360。 Table 194: In the general formula IW 1 -0, when R 1 =NHCH 3 and R 2 =ethoxycarbonyl, the substituent R is consistent with Table 1, and the representative compound number is 194.1-194.360, corresponding to 1.1- in Table 1 in turn 1.360.
表195：通式I-W 1-0中，当R 1＝NHCH 2CH 3且R 2＝乙氧基羰基时，取代基R与表1一致，代表化合物编号为195.1-195.360，依次对应表1的1.1-1.360。 Table 195: In the general formula IW 1 -0, when R 1 =NHCH 2 CH 3 and R 2 =ethoxycarbonyl, the substituent R is consistent with Table 1, and represents the compound number of 195.1-195.360, corresponding to Table 1 in turn 1.1-1.360.
表196：通式I-W 1-0中，当R 1＝N(CH 3) 2且R 2＝乙氧基羰基时，取代基R与表1一致，代表化合物编号为196.1-196.360，依次对应表1的1.1-1.360。 Table 196: In the general formula IW 1 -0, when R 1 =N(CH 3 ) 2 and R 2 =ethoxycarbonyl, the substituent R is consistent with Table 1, which represents compound numbers 196.1-196.360, corresponding to the table in turn 1 of 1.1-1.360.
表197：通式I-W 1-0中，当R 1＝OCH 3且R 2＝乙氧基羰基时，取代基R与表1一致，代表化合物编号为197.1-197.360，依次对应表1的1.1-1.360。 Table 197: In the general formula IW 1 -0, when R 1 =OCH 3 and R 2 =ethoxycarbonyl, the substituent R is consistent with Table 1, and the representative compound number is 197.1-197.360, corresponding to 1.1- in Table 1 in turn 1.360.
表198：通式I-W 1-0中，当R 1＝OCH 2CH 3且R 2＝乙氧基羰基时，取代基R与表1一致，代表化合物编号为198.1-198.360，依次对应表1的1.1-1.360。 Table 198: In the general formula IW 1 -0, when R 1 =OCH 2 CH 3 and R 2 =ethoxycarbonyl, the substituent R is consistent with Table 1, and represents the compound number 198.1-198.360, corresponding to Table 1 in turn 1.1-1.360.
通式I中，当W＝W 9，Z 1＝Z 2＝Z 3＝Z 4＝Z 5＝Z 6＝Z 7＝H且n＝0时，通式I化合物以通式I-W 9表示。 When the formula I, where W = W 9, Z 1 = Z 2 = Z 3 = Z 4 = Z 5 = Z 6 = Z 7 = H and n = 0, compounds of Formula I represented by the general formula IW 9.
Figure PCTCN2020073096-appb-000008
Figure PCTCN2020073096-appb-000008
表199：通式I-W 9中，当R 2＝H时，R 1为不同的取代基见表199，代表化合物编号为199.1-199.9。 Table 199: In the general formula IW 9 , when R 2 =H, R 1 is a different substituent. See Table 199, which represents compound numbers from 199.1-199.9.
表199Table 199
编号Numbering R 1 R 1 编号Numbering R 1 R 1 编号Numbering R 1 R 1
199.1199.1 HH 199.2199.2 CH 3 CH 3 199.3199.3 CH 2CH 3 CH 2 CH 3
199.4199.4 SCH 3 SCH 3 199.5199.5 SCH 2CH 3 SCH 2 CH 3 199.6199.6 NH 2 NH 2
199.7199.7 NHCH 3 NHCH 3 199.8199.8 OCH 3 OCH 3 199.9199.9 OCH 2CH 3 OCH 2 CH 3
表200：通式I-W 9中，当R 2＝CH 3时，R 1为不同的取代基与表199一致，代表化合物编号为200.1-200.9，依次对应表199的199.1-199.9。 Table 200: In the general formula IW 9 , when R 2 =CH 3 , R 1 is a different substituent. It is consistent with Table 199, representing the compound number 200.1-200.9, corresponding to 199.1-199.9 in Table 199 in turn.
表201：通式I-W 9中，当R 2＝CH 2CH 3时，R 1为不同的取代基与表199一致，代表化合物编号为201.1-201.9，依次对应表199的199.1-199.9。 Table 201: In the general formula IW 9 , when R 2 =CH 2 CH 3 , R 1 is a different substituent. It is consistent with Table 199, representing the compound number 201.1-201.9, corresponding to 199.1-199.9 in Table 199 in turn.
表202：通式I-W 9中，当R 2＝乙酰基时，R 1为不同的取代基与表199一致，代表化合物编号为202.1-202.9，依次对应表199的199.1-199.9。 Table 202: In the general formula IW 9 , when R 2 = acetyl, R 1 is a different substituent. It is consistent with Table 199, and the representative compound number is 202.1-202.9, corresponding to 199.1-199.9 in Table 199 in turn.
表203：通式I-W 9中，当R 2＝甲氧基羰基时，R 1为不同的取代基与表199一致，代表化合物编号为203.1-203.9，依次对应表199的199.1-199.9。 Table 203: In the general formula IW 9 , when R 2 = methoxycarbonyl, R 1 is a different substituent. It is consistent with Table 199, representing the compound number 203.1-203.9, corresponding to 199.1-199.9 in Table 199 in turn.
表204：通式I-W 9中，当R 2＝乙氧基羰基时，R 1为不同的取代基与表199一致，代表化合物编号为204.1-204.9，依次对应表199的199.1-199.9。 Table 204: In the general formula IW 9 , when R 2 = ethoxycarbonyl, R 1 is a different substituent. It is consistent with Table 199, representing the compound number 204.1-204.9, corresponding to 199.1-199.9 in Table 199 in turn.
通式I中，当W＝W 10，Z 1＝Z 2＝Z 3＝Z 4＝Z 5＝Z 6＝Z 7＝H且n＝0时，通式I化合物以通式I-W 10表示。 When the formula I, where W = W 10, Z 1 = Z 2 = Z 3 = Z 4 = Z 5 = Z 6 = Z 7 = H and n = 0, the formula I compounds represented by the general formula IW 10.
Figure PCTCN2020073096-appb-000009
Figure PCTCN2020073096-appb-000009
表205：通式I-W 10中，当R 2＝H时，R 1为不同的取代基与表199一致，代表化合物编号为205.1-205.9，依次对应表199的199.1-199.9。 Table 205: In the general formula IW 10 , when R 2 =H, R 1 is a different substituent. It is consistent with Table 199, and the representative compound number is 205.1-205.9, corresponding to 199.1-199.9 in Table 199 in turn.
表206：通式I-W 10中，当R 2＝CH 3时，R 1为不同的取代基与表199一致，代表化合物编号为206.1-206.9，依次对应表199的199.1-199.9。 Table 206: In the general formula IW 10 , when R 2 =CH 3 , R 1 is a different substituent. It is consistent with Table 199, representing the compound number 206.1-206.9, corresponding to 199.1-199.9 in Table 199 in turn.
表207：通式I-W 10中，当R 2＝CH 2CH 3时，R 1为不同的取代基与表199一致，代表化合物编号为207.1-207.9，依次对应表199的199.1-199.9。 Table 207: In the general formula IW 10 , when R 2 =CH 2 CH 3 , R 1 is a different substituent. It is consistent with Table 199, representing compound numbers 207.1-207.9, corresponding to 199.1-199.9 in Table 199 in turn.
表208：通式I-W 10中，当R 2＝乙酰基时，R 1为不同的取代基与表199一致，代表化合物编号为208.1-208.9，依次对应表199的199.1-199.9。 Table 208: In the general formula IW 10 , when R 2 = acetyl, R 1 is a different substituent. It is consistent with Table 199, and the representative compound number is 208.1-208.9, corresponding to 199.1-199.9 in Table 199 in turn.
表209：通式I-W 10中，当R 2＝甲氧基羰基时，R 1为不同的取代基与表199一致，代表化合物编号为209.1-209.9，依次对应表199的199.1-199.9。 Table 209: In the general formula IW 10 , when R 2 = methoxycarbonyl, R 1 is a different substituent. It is consistent with Table 199, representing the compound number of 209.1-209.9, corresponding to 199.1-199.9 of Table 199 in turn.
表210：通式I-W 10中，当R 2＝乙氧基羰基时，R 1为不同的取代基与表199一致，代表化合物编号为210.1-210.9，依次对应表199的199.1-199.9。 Table 210: In the general formula IW 10 , when R 2 = ethoxycarbonyl, R 1 is a different substituent. It is consistent with Table 199 and represents compound numbers 210.1-210.9, corresponding to 199.1-199.9 in Table 199 in turn.
通式I中，当W＝W 2，Y 1＝Y 2＝Y 3＝Y 4＝H且n＝1时，通式I化合物以通式I-W 2表示。 Formula I, where W = W 2, Y 1 = Y 2 = Y 3 = Y 4 = H and n = 1, compounds of Formula I represented by Formula IW 2.
Figure PCTCN2020073096-appb-000010
Figure PCTCN2020073096-appb-000010
表211：通式I-W 2中，当R 2＝H时，R 1为不同的取代基与表199一致，代表化合物编号为211.1-211.9，依次对应表199的199.1-199.9。 Table 211: In the general formula IW 2 , when R 2 =H, R 1 is a different substituent. It is consistent with Table 199, and the representative compound number is 211.1-211.9, corresponding to 199.1-199.9 in Table 199 in turn.
通式I中，当W＝W 3，Y 1＝Y 2＝Y 3＝Y 4＝H且n＝1时，通式I化合物以通式I-W 3表示。 Formula I, when W = W 3, Y 1 = Y 2 = Y 3 = Y 4 = H and n = 1, compounds of Formula I represented by Formula 3 IW.
Figure PCTCN2020073096-appb-000011
Figure PCTCN2020073096-appb-000011
表212：通式I-W 3中，当R 2＝H时，R 1为不同的取代基与表199一致，代表化合物编号为212.1-212.9，依次对应表199的199.1-199.9。 Table 212: In the general formula IW 3 , when R 2 =H, R 1 is a different substituent. It is consistent with Table 199, representing compound numbers 212.1-212.9, corresponding to 199.1-199.9 in Table 199 in turn.
通式I中，当W＝W 4，Y 1＝Y 2＝Y 3＝Y 4＝H且n＝1时，通式I化合物以通式I-W 4表示。 Formula I, where W = W 4, Y 1 = Y 2 = Y 3 = Y 4 = H and n = 1, compounds of Formula I represented by Formula 4 IW.
Figure PCTCN2020073096-appb-000012
Figure PCTCN2020073096-appb-000012
表213：通式I-W 4中，当R 2＝H时，R 1为不同的取代基与表199一致，代表化合物编号为213.1-213.9，依次对应表199的199.1-199.9。 Table 213: In the general formula IW 4 , when R 2 =H, R 1 is a different substituent. It is consistent with Table 199, representing compound numbers 213.1-213.9, corresponding to 199.1-199.9 in Table 199 in turn.
通式I中，当W＝W 5，Y 1＝Y 2＝Y 3＝H且n＝1时，通式I化合物以通式I-W 5表示。 When the formula I, where W = W 5, Y 1 = Y 2 = Y 3 = H and n = 1, compounds of Formula I represented by Formula IW 5.
Figure PCTCN2020073096-appb-000013
Figure PCTCN2020073096-appb-000013
表214：通式I-W 5中，当R 2＝H时，R 1为不同的取代基与表199一致，代表化合物编号为214.1-214.9，依次对应表199的199.1-199.9。 Table 214: In the general formula IW 5 , when R 2 =H, R 1 is a different substituent. It is consistent with Table 199, representing compound numbers 214.1-214.9, corresponding to 199.1-199.9 in Table 199 in turn.
通式I中，当W＝W 6，Y 1＝Y 2＝Y 3＝H且n＝1时，通式I化合物以通式I-W 6表示。 Formula I, when W = W 6, Y 1 = Y 2 = Y 3 = H and n = 1, compounds of Formula I represented by Formula IW 6.
Figure PCTCN2020073096-appb-000014
Figure PCTCN2020073096-appb-000014
表215：通式I-W 6中，当R 2＝H时，R 1为不同的取代基与表199一致，代表化合物编号为215.1-215.9，依次对应表199的199.1-199.9。 Table 215: In the general formula IW 6 , when R 2 =H, R 1 is a different substituent. It is consistent with Table 199, representing compound numbers 215.1-215.9, corresponding to 199.1-199.9 in Table 199 in turn.
通式I中，当W＝W 7，Y 1＝Y 2＝Y 3＝H且n＝1时，通式I化合物以通式I-W 7表示。 Formula I, when W = W 7, Y 1 = Y 2 = Y 3 = H and n = 1, compounds of Formula I represented by Formula 7 IW.
Figure PCTCN2020073096-appb-000015
Figure PCTCN2020073096-appb-000015
Figure PCTCN2020073096-appb-000016
Figure PCTCN2020073096-appb-000016
表216：通式I-W 7中，当R 2＝H时，R 1为不同的取代基与表199一致，代表化合物编号为216.1-216.9，依次对应表199的199.1-199.9。 Table 216: In the general formula IW 7 , when R 2 =H, R 1 is a different substituent. It is consistent with Table 199, representing compound numbers 216.1-216.9, corresponding to 199.1-199.9 in Table 199 in turn.
通式I中，当W＝W 8，Y 1＝Y 2＝Y 3＝H且n＝1时，通式I化合物以通式I-W 8表示。 Formula I, when W = W 8, Y 1 = Y 2 = Y 3 = H and n = 1, compounds of Formula I represented by Formula 8 IW.
Figure PCTCN2020073096-appb-000017
Figure PCTCN2020073096-appb-000017
表217：通式I-W 8中，当R 2＝H时，R 1为不同的取代基与表199一致，代表化合物编号为217.1-217.9，依次对应表199的199.1-199.9。 Table 217: In the general formula IW 8 , when R 2 =H, R 1 is a different substituent. It is consistent with Table 199, representing compound numbers 217.1-217.9, corresponding to 199.1-199.9 in Table 199 in turn.
表218：如下化合物，Table 218: The following compounds,
表218Table 218
Figure PCTCN2020073096-appb-000018
Figure PCTCN2020073096-appb-000018
本发明部分化合物的物化性质如表219所示，其核磁及质谱数据如表220所示：The physical and chemical properties of some of the compounds of the present invention are shown in Table 219, and their nuclear magnetic and mass spectrometry data are shown in Table 220:
表219Table 219
Figure PCTCN2020073096-appb-000019
Figure PCTCN2020073096-appb-000019
Figure PCTCN2020073096-appb-000020
Figure PCTCN2020073096-appb-000020
Figure PCTCN2020073096-appb-000021
Figure PCTCN2020073096-appb-000021
Figure PCTCN2020073096-appb-000022
Figure PCTCN2020073096-appb-000022
Figure PCTCN2020073096-appb-000023
Figure PCTCN2020073096-appb-000023
Figure PCTCN2020073096-appb-000024
Figure PCTCN2020073096-appb-000024
Figure PCTCN2020073096-appb-000025
Figure PCTCN2020073096-appb-000025
注：表219中“-”表示无cas号。Note: "-" in Table 219 means no cas number.
表220Table 220
Figure PCTCN2020073096-appb-000026
Figure PCTCN2020073096-appb-000026
Figure PCTCN2020073096-appb-000027
Figure PCTCN2020073096-appb-000027
Figure PCTCN2020073096-appb-000028
Figure PCTCN2020073096-appb-000028
Figure PCTCN2020073096-appb-000029
Figure PCTCN2020073096-appb-000029
Figure PCTCN2020073096-appb-000030
Figure PCTCN2020073096-appb-000030
本发明的通式I化合物可按照以下方法制备(式中各基团除另有说明外定义同前)：The compound of general formula I of the present invention can be prepared according to the following method (each group in the formula is defined as above unless otherwise specified):
方法1：当R 1为氢或C 1-C 6烷基时，通式I化合物可按以下方法进行制备(式中Alkoxyl表示C 1-C 6烷氧基，如甲氧基、乙氧基等)： Method 1: When R 1 is hydrogen or C 1 -C 6 alkyl, the compound of general formula I can be prepared by the following method (where Alkoxyl represents C 1 -C 6 alkoxy, such as methoxy, ethoxy Wait):
Figure PCTCN2020073096-appb-000031
Figure PCTCN2020073096-appb-000031
通式II-1化合物与通式III-1化合物在适宜的溶剂中，在温度从-10℃到溶剂沸点下反应0.5-48小时可制得通式I-1化合物；反应可在碱存在进行。The compound of general formula II-1 and the compound of general formula III-1 are reacted in a suitable solvent at a temperature from -10°C to the boiling point of the solvent for 0.5-48 hours to obtain a compound of general formula I-1; the reaction can be carried out in the presence of a base .
通式I-1化合物与烷基化试剂(如碘甲烷、碘乙烷、碘丙烷、硫酸二甲酯、硫酸二乙酯、2,2,2-三氟碘乙烷、氯乙腈、溴乙腈等)或酰基化试剂(如乙酰氯、正丙酰氯、乙酸酐、环丙基甲酰氯、氯甲酸甲酯、氯甲酸乙酯等)在适宜的溶剂中，在温度从-10℃到溶剂沸点下反应0.5-48小时可制得通式I-2化合物；反应可在碱存在进行。Compounds of general formula I-1 and alkylating reagents (such as methyl iodide, ethyl iodide, propane iodide, dimethyl sulfate, diethyl sulfate, 2,2,2-trifluoroiodoethane, chloroacetonitrile, bromoacetonitrile Etc.) or acylating reagents (such as acetyl chloride, n-propionyl chloride, acetic anhydride, cyclopropylformyl chloride, methyl chloroformate, ethyl chloroformate, etc.) in a suitable solvent at a temperature from -10°C to the boiling point of the solvent The compound of general formula I-2 can be prepared by reacting for 0.5-48 hours; the reaction can be carried out in the presence of a base.
上述反应中，适宜的溶剂可相同或不同，可为醇类(如，甲醇、乙醇等)、芳烃类(如，苯、甲苯、二甲苯等)、酮类(如，丙酮、甲乙酮、甲基异丁基酮等)、卤代烃类(如，氯仿、二氯甲烷等)、酯类(如，乙酸甲酯、乙酸乙酯等)、醚类(如，四氢呋喃、二噁烷、二乙醚、1,2-二甲氧基乙烷等)、极性溶剂类(如，水、乙腈、二氧六环、N,N-二甲基甲酰胺、N-甲基吡咯烷酮、二甲基亚砜等)或上述溶剂的混合溶剂。碱可相同或不同，可为三甲胺、三乙胺、吡啶、DBU、4-二甲氨基吡啶等有机碱(如，三甲胺、三乙胺、吡啶、DBU、4-二甲氨基吡啶等)、碱金属氢化物(如，氢化钠、氢化钾等)、碱金属氢氧化物(如，氢氧化钠、氢氧化钾等)、碱土类金属氢氧化物(如，氢氧化钙等)、碱金属碳酸盐(如，碳酸钠、碳酸钾等)、碱金属碳酸氢盐(如，碳酸氢钠等)、金属醇盐(如，甲醇钠、乙醇钠、乙醇钾、叔丁醇钾、叔丁醇钠等)。In the above reaction, suitable solvents can be the same or different, and can be alcohols (e.g., methanol, ethanol, etc.), aromatic hydrocarbons (e.g., benzene, toluene, xylene, etc.), ketones (e.g., acetone, methyl ethyl ketone, methyl Isobutyl ketone, etc.), halogenated hydrocarbons (such as chloroform, dichloromethane, etc.), esters (such as methyl acetate, ethyl acetate, etc.), ethers (such as tetrahydrofuran, dioxane, diethyl ether) , 1,2-dimethoxyethane, etc.), polar solvents (such as water, acetonitrile, dioxane, N,N-dimethylformamide, N-methylpyrrolidone, dimethylene Sulfone, etc.) or a mixed solvent of the above solvents. The bases can be the same or different, and can be organic bases such as trimethylamine, triethylamine, pyridine, DBU, 4-dimethylaminopyridine (eg, trimethylamine, triethylamine, pyridine, DBU, 4-dimethylaminopyridine, etc.) , Alkali metal hydrides (such as sodium hydride, potassium hydride, etc.), alkali metal hydroxides (such as sodium hydroxide, potassium hydroxide, etc.), alkaline earth metal hydroxides (such as calcium hydroxide, etc.), alkali Metal carbonates (such as sodium carbonate, potassium carbonate, etc.), alkali metal bicarbonates (such as sodium bicarbonate, etc.), metal alkoxides (such as sodium methoxide, sodium ethoxide, potassium ethoxide, potassium tert-butoxide, tertiary Sodium butoxide, etc.).
方法2：当R 1为C 1-C 6烷硫基或卤代C 1-C 6烷硫基时，通式I化合物可按以下方法进行制备(式中A表示C 1-C 6烷基或卤代C 1-C 6烷基)： Method 2: When R 1 is C 1 -C 6 alkylthio or halogenated C 1 -C 6 alkylthio, the compound of general formula I can be prepared according to the following method (where A represents C 1 -C 6 alkyl Or halogenated C 1 -C 6 alkyl):
Figure PCTCN2020073096-appb-000032
Figure PCTCN2020073096-appb-000032
通式II-2化合物与通式III-1化合物在适宜的溶剂中，在温度从-10℃到溶剂沸点下反应0.5-48小时可制得通式I-3化合物；在该反应中，通式II-2化合物:通式III-1化合物≥1:1(摩尔比)；反应可在碱存在进行。Compounds of general formula II-2 and compounds of general formula III-1 are reacted in a suitable solvent at a temperature from -10°C to the boiling point of the solvent for 0.5-48 hours to obtain compounds of general formula I-3; in this reaction, Compound of formula II-2: compound of general formula III-1 ≥ 1:1 (molar ratio); the reaction can be carried out in the presence of a base.
由通式I-3化合物制备通式I-4化合物的方法与由通式I-1化合物制备通式I-2化合物的方法相同。The method of preparing the compound of general formula I-4 from the compound of general formula I-3 is the same as the method of preparing the compound of general formula I-2 from the compound of general formula I-1.
上述反应中，适宜的溶剂可相同或不同，可为醇类(如，甲醇、乙醇等)、芳烃类(如，苯、甲苯、二甲苯等)、酮类(如，丙酮、甲乙酮、甲基异丁基酮等)、卤代烃类(如，氯仿、二氯甲烷等)、酯类(如，乙酸甲酯、乙酸乙酯等)、醚类(如，四氢呋喃、二噁烷、二乙醚、1,2-二甲氧基乙烷等)、极性溶剂类(如，水、乙腈、二氧六环、N,N-二甲基甲酰胺、N-甲基吡咯烷酮、二甲基亚砜等)或上述溶剂的混合溶剂。碱可相同或不同，可为三甲胺、三乙胺、吡啶、DBU、4-二甲氨基吡啶等有机碱(如，三甲胺、三乙胺、吡啶、DBU、4-二甲氨基吡啶等)、碱金属氢化物(如，氢化钠、氢化钾等)、碱金属氢氧化物(如，氢氧化钠、氢氧化钾等)、碱土类金属氢氧化物(如，氢氧化钙等)、碱金属碳酸盐(如，碳酸钠、碳酸钾等)、碱金属碳酸氢盐(如，碳酸氢钠等)、金属醇盐(如，甲醇钠、乙醇钠、乙醇钾、叔丁醇钾、叔丁醇钠等)。In the above reaction, suitable solvents can be the same or different, and can be alcohols (e.g., methanol, ethanol, etc.), aromatic hydrocarbons (e.g., benzene, toluene, xylene, etc.), ketones (e.g., acetone, methyl ethyl ketone, methyl Isobutyl ketone, etc.), halogenated hydrocarbons (such as chloroform, dichloromethane, etc.), esters (such as methyl acetate, ethyl acetate, etc.), ethers (such as tetrahydrofuran, dioxane, diethyl ether) , 1,2-dimethoxyethane, etc.), polar solvents (such as water, acetonitrile, dioxane, N,N-dimethylformamide, N-methylpyrrolidone, dimethylene Sulfone, etc.) or a mixed solvent of the above solvents. The bases can be the same or different, and can be organic bases such as trimethylamine, triethylamine, pyridine, DBU, 4-dimethylaminopyridine (eg, trimethylamine, triethylamine, pyridine, DBU, 4-dimethylaminopyridine, etc.) , Alkali metal hydrides (such as sodium hydride, potassium hydride, etc.), alkali metal hydroxides (such as sodium hydroxide, potassium hydroxide, etc.), alkaline earth metal hydroxides (such as calcium hydroxide, etc.), alkali Metal carbonates (such as sodium carbonate, potassium carbonate, etc.), alkali metal bicarbonates (such as sodium bicarbonate, etc.), metal alkoxides (such as sodium methoxide, sodium ethoxide, potassium ethoxide, potassium tert-butoxide, tertiary Sodium butoxide, etc.).
方法3：当R 1为羟基、巯基、氨基或C 1-C 6烷基氨基时，通式I化合物可按以下方法进行制备： Method 3: When R 1 is a hydroxyl group, a mercapto group, an amino group or a C 1 -C 6 alkylamino group, the compound of general formula I can be prepared as follows:
Figure PCTCN2020073096-appb-000033
Figure PCTCN2020073096-appb-000033
通式I-3化合物与亲核试剂在适宜的溶剂中，在温度从-10℃到溶剂沸点下反应0.5-48小时可制得通式I-5化合物；通式I-4化合物与亲核试剂在适宜的溶剂中，在温度从-10℃到溶剂沸点下反应0.5-48小时可制得通式I-6化合物。Compounds of general formula I-3 and nucleophiles are reacted in a suitable solvent at a temperature from -10°C to the boiling point of the solvent for 0.5-48 hours to prepare compounds of general formula I-5; compounds of general formula I-4 and nucleophiles The reagents are reacted in a suitable solvent at a temperature from -10°C to the boiling point of the solvent for 0.5-48 hours to prepare a compound of general formula I-6.
上述反应中，亲核试剂为氢氧化钠、氢氧化钾、氢氧化锂、硫氢化钠、氨基钠、氨水、C 1-C 6烷基氨(如甲胺、乙胺等)或其盐酸盐(如甲胺盐酸盐、乙胺盐酸盐等)。 In the above reaction, the nucleophile is sodium hydroxide, potassium hydroxide, lithium hydroxide, sodium hydrosulfide, sodium amide, ammonia, C 1 -C 6 alkyl ammonia (such as methylamine, ethylamine, etc.) or its hydrochloric acid Salt (such as methylamine hydrochloride, ethylamine hydrochloride, etc.).
上述反应中，当亲核试剂为C 1-C 6烷基氨盐酸盐时，反应需要适宜的碱参与，以中和盐酸盐，适宜的碱优选三甲胺、三乙胺、吡啶、碳酸钾、碳酸钠、碳酸氢钾、碳酸氢钠等。 In the above reaction, when the nucleophile is C 1 -C 6 alkyl ammonia hydrochloride, the reaction requires the participation of a suitable base to neutralize the hydrochloride. Suitable bases are preferably trimethylamine, triethylamine, pyridine, and carbonic acid. Potassium, sodium carbonate, potassium bicarbonate, sodium bicarbonate, etc.
上述反应中，适宜的溶剂可相同或不同，可为醇类(如，甲醇、乙醇等)、芳烃类(如，苯、甲苯、二甲苯等)、酮类(如，丙酮、甲乙酮、甲基异丁基酮等)、卤代烃类(如，氯仿、二氯甲烷等)、酯类(如，乙酸甲酯、乙酸乙酯等)、醚类(如，四氢呋喃、二噁烷、二乙醚、1,2-二甲氧基乙烷等)、极性溶剂类(如，水、乙腈、二氧六环、N,N-二甲基甲酰胺、N-甲基吡咯烷酮、二甲基亚砜等)或上述溶剂的混合溶剂。In the above reaction, suitable solvents can be the same or different, and can be alcohols (e.g., methanol, ethanol, etc.), aromatic hydrocarbons (e.g., benzene, toluene, xylene, etc.), ketones (e.g., acetone, methyl ethyl ketone, methyl Isobutyl ketone, etc.), halogenated hydrocarbons (such as chloroform, dichloromethane, etc.), esters (such as methyl acetate, ethyl acetate, etc.), ethers (such as tetrahydrofuran, dioxane, diethyl ether) , 1,2-dimethoxyethane, etc.), polar solvents (such as water, acetonitrile, dioxane, N,N-dimethylformamide, N-methylpyrrolidone, dimethylene Sulfone, etc.) or a mixed solvent of the above solvents.
方法4：当R 1为氰基、C 1-C 6烷氧基、卤代C 1-C 6烷氧基或C 1-C 6二烷基氨基时，通式I化合物可按以下方法进行制备： Method 4: When R 1 is cyano, C 1 -C 6 alkoxy, halogenated C 1 -C 6 alkoxy or C 1 -C 6 dialkylamino, the compound of general formula I can be carried out as follows preparation:
Figure PCTCN2020073096-appb-000034
Figure PCTCN2020073096-appb-000034
通式I-3化合物与亲核试剂在适宜的溶剂中，在温度从-10℃到溶剂沸点下反应0.5-48小时可制得通式I-7化合物；通式I-4化合物与亲核试剂在适宜的溶剂中，在温度从-10℃到溶剂沸点下反应0.5-48小时可制得通式I-8化合物。Compounds of general formula I-3 and nucleophiles are reacted in a suitable solvent at a temperature from -10°C to the boiling point of the solvent for 0.5-48 hours to prepare compounds of general formula I-7; compounds of general formula I-4 and nucleophiles The reagents are reacted in a suitable solvent at a temperature from -10°C to the boiling point of the solvent for 0.5-48 hours to prepare a compound of general formula I-8.
上述反应中，亲核试剂为氰化钠、氰化钾、C 1-C 6烷醇的碱金属盐(如甲醇钠、甲醇钾、乙醇钠、乙醇钾等)、卤代C 1-C 6烷醇的碱金属盐(如2,2,2-三氟乙醇钠或2,2,2-三氟乙醇钾等)、C 1-C 6二烷基氨(如N,N-二甲基氨、N-甲基-N-乙基氨等)或其盐酸盐(如N,N-二甲基氨盐酸盐、N-甲基-N-乙基氨盐酸盐等)。 In the above reaction, the nucleophile is sodium cyanide, potassium cyanide, alkali metal salts of C 1 -C 6 alkanols (such as sodium methoxide, potassium methoxide, sodium ethoxide, potassium ethoxide, etc.), halogenated C 1 -C 6 Alkali metal salt of alkanol (such as sodium 2,2,2-trifluoroethoxide or potassium 2,2,2-trifluoroethoxide, etc.), C 1 -C 6 dialkyl ammonia (such as N,N-dimethyl Ammonia, N-methyl-N-ethylamine, etc.) or its hydrochloride (such as N,N-dimethylammonium hydrochloride, N-methyl-N-ethylammonium hydrochloride, etc.).
上述反应中，当亲核试剂为C 1-C 6二烷基氨盐酸盐时，反应需要适宜的碱参与，以中和盐酸盐，适宜的碱优选三甲胺、三乙胺、吡啶、碳酸钾、碳酸钠、碳酸氢钾、碳酸氢钠等。 In the above reaction, when the nucleophile is C 1 -C 6 dialkylamine hydrochloride, the reaction requires the participation of a suitable base to neutralize the hydrochloride. Suitable bases are preferably trimethylamine, triethylamine, pyridine, Potassium carbonate, sodium carbonate, potassium bicarbonate, sodium bicarbonate, etc.
上述反应中，适宜的溶剂可相同或不同，可为醇类(如，甲醇、乙醇等)、芳烃类(如，苯、甲苯、二甲苯等)、酮类(如，丙酮、甲乙酮、甲基异丁基酮等)、卤代烃类(如，氯仿、二氯甲烷等)、酯类(如，乙酸甲酯、乙酸乙酯等)、醚类(如，四氢呋喃、二噁烷、二乙醚、1,2-二甲氧基乙烷等)、极性溶剂类(如，水、乙腈、二氧六环、N,N-二甲基甲酰胺、N-甲基吡咯烷酮、二甲基亚砜等)或上述溶剂的混合溶剂。In the above reaction, suitable solvents can be the same or different, and can be alcohols (e.g., methanol, ethanol, etc.), aromatic hydrocarbons (e.g., benzene, toluene, xylene, etc.), ketones (e.g., acetone, methyl ethyl ketone, methyl Isobutyl ketone, etc.), halogenated hydrocarbons (such as chloroform, dichloromethane, etc.), esters (such as methyl acetate, ethyl acetate, etc.), ethers (such as tetrahydrofuran, dioxane, diethyl ether) , 1,2-dimethoxyethane, etc.), polar solvents (such as water, acetonitrile, dioxane, N,N-dimethylformamide, N-methylpyrrolidone, dimethylene Sulfone, etc.) or a mixed solvent of the above solvents.
由通式I-7化合物制备通式I-8化合物的方法与由通式I-1化合物制备通式I-2化合物的方法相同。The method for preparing compounds of general formula I-8 from compounds of general formula I-7 is the same as the method for preparing compounds of general formula I-2 from compounds of general formula I-1.
方法5：当R 2为C 1-C 6烷基、卤代C 1-C 6烷基或氰基C 1-C 6烷基时，通式I化合物可按以下方法进行制备： Method 5: When R 2 is C 1 -C 6 alkyl, halo C 1 -C 6 alkyl or cyano C 1 -C 6 alkyl, the compound of general formula I can be prepared as follows:
(1)当R 1为氢或C 1-C 6烷基时： (1) When R 1 is hydrogen or C 1 -C 6 alkyl:
Figure PCTCN2020073096-appb-000035
Figure PCTCN2020073096-appb-000035
通式II-1化合物与通式III-2化合物反应可制得通式I-9化合物。The compound of general formula II-1 can be prepared by reacting compound of general formula III-2 with compound of general formula I-9.
由通式II-1化合物制备通式I-9化合物的方法与由通式II-1化合物制备通式I-1化合物的方法相同。The method for preparing the compound of the general formula I-9 from the compound of the general formula II-1 is the same as the method for preparing the compound of the general formula I-1 from the compound of the general formula II-1.
(2)当R 1不为氢或C 1-C 6烷基时(式中K表示羟基、巯基、氨基、氰基、C 1-C 6烷氧基、卤代C 1-C 6烷氧基、C 1-C 6烷基氨基或C 1-C 6二烷基氨基)： (2) When R 1 is not hydrogen or C 1 -C 6 alkyl (where K represents hydroxyl, mercapto, amino, cyano, C 1 -C 6 alkoxy, halogenated C 1 -C 6 alkoxy Group, C 1 -C 6 alkylamino or C 1 -C 6 dialkylamino):
Figure PCTCN2020073096-appb-000036
Figure PCTCN2020073096-appb-000036
通式II-2化合物与通式III-2化合物反应可制得通式I-10化合物。The compound of general formula II-2 can be reacted with compound of general formula III-2 to prepare compound of general formula I-10.
由通式II-2化合物制备通式I-10化合物的方法与由通式II-2化合物制备通式I-3化合物的方法相同。The method for preparing the compound of the general formula I-10 from the compound of the general formula II-2 is the same as the method for preparing the compound of the general formula I-3 from the compound of the general formula II-2.
通式I-10化合物与亲核试剂反应可制得通式I-11化合物。The compound of general formula I-10 can be prepared by reacting the compound of general formula I-10 with a nucleophile.
由通式I-10化合物制备通式I-11化合物与由通式I-4化合物制备通式I-6化合物或由通式I-4化合物制备通式I-8化合物的方法相同。The method for preparing the compound of the general formula I-11 from the compound of the general formula I-10 is the same as the method for preparing the compound of the general formula I-6 from the compound of the general formula I-4 or preparing the compound of the general formula I-8 from the compound of the general formula I-4.
通式II-1化合物可以通过购买或按公知方法(例如US2503524、RSC Advances,6(29),24491-24500；2016、Huaxue Shiji,35(9),849-850；2013、WO2010019637、WO2014139326、WO2004009602、WO2005117909、WO2010086118中所描述的方法)制备。The compound of general formula II-1 can be purchased or according to known methods (for example, US2503524, RSC Advances, 6(29), 24491-24500; 2016, Huaxue Shiji, 35(9), 849-850; 2013, WO2010019637, WO2014139326, WO2004009602 , WO2005117909, WO2010086118).
通式II-2化合物可以通过购买或按公知方法(例如Organic Process Research&Development,15(3),556-564；2011、CN102001977、WO2018089786、Journal of Enzyme Inhibition and Medicinal Chemistry,28(1),163-171；2013中所描述的方法)制备。The compound of general formula II-2 can be purchased or according to known methods (e.g. Organic Process Research & Development, 15(3), 556-564; 2011, CN102001977, WO2018089786, Journal of Enzyme Inhibition and Medicinal Chemistry, 28(1), 163-171 ; The method described in 2013).
通式III-1化合物、通式III-2化合物及其它原料和试剂可以通过购买或者按照常规方法自制。The compound of general formula III-1, compound of general formula III-2 and other raw materials and reagents can be purchased or self-made according to conventional methods.
本发明通式I所示的化合物用于控制植物细菌性病害的用途，可用于防治多种植物细菌性病害，例如果斑病(如甜瓜果斑病等)、叶斑病(如番茄细菌性叶斑病等)、青枯病(如番茄青枯病、马铃薯青枯病等)、细菌性疫病、溃疡病(如柑橘溃疡病、猕猴桃溃疡病等)、软腐病(如大白菜软腐病等)、细菌性角斑病(如黄瓜细菌性角斑病等)、细菌性条斑病(如水稻细菌性条斑病等)、叶枯病、白叶枯病(如水稻白叶枯病等)、野火病和细菌性疮痂病等。The compound represented by the general formula I of the present invention is used to control plant bacterial diseases, and can be used to prevent and control a variety of plant bacterial diseases, such as fruit spot disease (such as melon fruit spot, etc.), leaf spot disease (such as tomato bacteria) Leaf spot disease, etc.), bacterial wilt (such as tomato bacterial wilt, potato bacterial wilt, etc.), bacterial blight, canker disease (such as citrus canker, kiwi fruit canker, etc.), soft rot (such as soft Chinese cabbage) Rot, etc.), bacterial angular leaf spot (such as cucumber bacterial angular leaf spot, etc.), bacterial leaf streak (such as rice bacterial leaf spot, etc.), leaf blight, bacterial leaf blight (such as rice white leaf Blight, etc.), wildfire and bacterial scab.
具体实施方式detailed description
以下具体实施例用来进一步说明本发明，但本发明绝非限于这些例子。(除另有注明外，所用原料均有市售)The following specific examples are used to further illustrate the present invention, but the present invention is by no means limited to these examples. (Unless otherwise noted, all raw materials used are commercially available)
合成实施例Synthesis Example
按照上述记载的合成路线，采用不同的原料化合物，即可分别制备获得本发明通式I所示化合物，进一步具体描述如下：According to the synthetic route described above, using different raw material compounds, the compounds represented by the general formula I of the present invention can be prepared separately, which are further described in detail as follows:
实施例1：化合物1.116的制备Example 1: Preparation of compound 1.116
Figure PCTCN2020073096-appb-000037
Figure PCTCN2020073096-appb-000037
50毫升反应瓶中加入3,4-二氯苄胺(0.30克，1.71毫摩尔)、乙氧基亚甲基丙二腈(0.22克，1.80毫摩尔)和20毫升乙醇，室温搅拌反应，TLC监测反应完毕后，减压蒸除大部分乙醇，冷却、过滤、得到白色固体0.42克。Add 3,4-dichlorobenzylamine (0.30 g, 1.71 mmol), ethoxymethylene malononitrile (0.22 g, 1.80 mmol) and 20 ml of ethanol to a 50 ml reaction flask. Stir at room temperature for reaction, TLC After monitoring the completion of the reaction, most of the ethanol was evaporated under reduced pressure, cooled and filtered to obtain 0.42 g of white solid.
实施例2：化合物1.360的制备Example 2: Preparation of compound 1.360
Figure PCTCN2020073096-appb-000038
Figure PCTCN2020073096-appb-000038
100毫升反应瓶中加入苄胺(2.00克，18.68毫摩尔)、乙氧基亚甲基丙二腈(2.28克，18.67毫摩尔)和50毫升乙醇，80℃回流反应，TLC监测反应完毕后，减压蒸除大部分乙醇，冷却、过滤、得到黄色固体3.08克。Add benzylamine (2.00 g, 18.68 mmol), ethoxymethylene malononitrile (2.28 g, 18.67 mmol) and 50 ml ethanol to a 100 ml reaction flask. The reaction was refluxed at 80°C. After the reaction was monitored by TLC, Most of the ethanol was evaporated under reduced pressure, cooled and filtered to obtain 3.08 g of yellow solid.
实施例3：化合物2.116的制备Example 3: Preparation of compound 2.116
Figure PCTCN2020073096-appb-000039
Figure PCTCN2020073096-appb-000039
100毫升反应瓶中加入3,4-二氯苄胺(1.00克，5.71毫摩尔)、2-(1-乙氧基亚乙 基)丙二腈(0.78克，5.73毫摩尔)和50毫升乙醇，80℃回流反应，TLC监测反应完毕后，减压蒸除大部分乙醇，冷却、过滤、得到白色固体1.36克。Add 3,4-dichlorobenzylamine (1.00 g, 5.71 mmol), 2-(1-ethoxyethylene) malononitrile (0.78 g, 5.73 mmol) and 50 ml ethanol into a 100 ml reaction flask The reaction was refluxed at 80°C. After the reaction was monitored by TLC, most of the ethanol was evaporated under reduced pressure, cooled and filtered to obtain 1.36 g of white solid.
实施例4：化合物2.360的制备Example 4: Preparation of compound 2.360
Figure PCTCN2020073096-appb-000040
Figure PCTCN2020073096-appb-000040
100毫升反应瓶中加入苄胺(1.00克，9.34毫摩尔)、2-(1-乙氧基亚乙基)丙二腈(1.27克，9.33毫摩尔)和50毫升乙醇，80℃回流反应，TLC监测反应完毕后，减压蒸除大部分乙醇，冷却、过滤、得到白色固体1.66克。Add benzylamine (1.00 g, 9.34 mmol), 2-(1-ethoxyethylene) malononitrile (1.27 g, 9.33 mmol) and 50 ml ethanol to a 100 ml reaction flask, and react under reflux at 80°C. After the reaction was monitored by TLC, most of the ethanol was evaporated under reduced pressure, cooled and filtered to obtain 1.66 g of white solid.
实施例5：化合物4.19的制备Example 5: Preparation of compound 4.19
Figure PCTCN2020073096-appb-000041
Figure PCTCN2020073096-appb-000041
50毫升反应瓶中加入2-甲基苄胺(0.50克，4.13毫摩尔)、2-(双(甲硫基)亚甲基)丙二腈(0.71克，4.18毫摩尔)和25毫升甲醇，65℃回流反应，TLC监测反应完毕后，减压蒸除大部分甲醇，冷却、过滤、得到白色固体0.90克。Add 2-methylbenzylamine (0.50 g, 4.13 mmol), 2-(bis(methylthio)methylene)malononitrile (0.71 g, 4.18 mmol) and 25 ml methanol into a 50 ml reaction flask, The reaction was refluxed at 65°C. After the reaction was monitored by TLC, most of the methanol was evaporated under reduced pressure, cooled, filtered, and 0.90 g of white solid was obtained.
原料2-(双(甲硫基)亚甲基)丙二腈可按公知方法进行制备，例如参照Organic Process Research&Development,15(3),556-564；2011所报道的方法。The raw material 2-(bis(methylthio)methylene)malononitrile can be prepared according to known methods, for example, refer to the method reported in Organic Process Research & Development, 15(3), 556-564; 2011.
实施例6：化合物4.360的制备Example 6: Preparation of compound 4.360
Figure PCTCN2020073096-appb-000042
Figure PCTCN2020073096-appb-000042
100毫升反应瓶中加入苄胺(1.00克，9.34毫摩尔)、2-(双(甲硫基)亚甲基)丙二腈(1.59克，9.35毫摩尔)和50毫升甲醇，65℃回流反应，TLC监测反应完毕后，减压蒸除大部分甲醇，冷却、过滤、得到白色固体2.14克。Add benzylamine (1.00 g, 9.34 mmol), 2-(bis(methylthio)methylene)malononitrile (1.59 g, 9.35 mmol) and 50 ml methanol to a 100 ml reaction flask, and react at 65°C under reflux After the reaction was monitored by TLC, most of the methanol was evaporated under reduced pressure, cooled and filtered to obtain 2.14 g of white solid.
实施例7：化合物6.19的制备Example 7: Preparation of Compound 6.19
Figure PCTCN2020073096-appb-000043
Figure PCTCN2020073096-appb-000043
称取化合物4.19(0.50克，2.06毫摩尔)、氨水(0.72克，20.55毫摩尔)和100毫升乙醇，置于250毫升反应瓶中，80℃回流反应，TLC监测反应完毕后，减压脱溶、柱层析后得到白色固体0.40克。Weigh compound 4.19 (0.50 g, 2.06 mmol), ammonia (0.72 g, 20.55 mmol) and 100 ml of ethanol, put them in a 250 ml reaction flask, and reflux at 80°C for reaction. After the reaction is monitored by TLC, the solution is removed under reduced pressure After column chromatography, 0.40 g of white solid is obtained.
实施例8：化合物6.360的制备Example 8: Preparation of Compound 6.360
Figure PCTCN2020073096-appb-000044
Figure PCTCN2020073096-appb-000044
称取化合物4.360(0.15克，4.37毫摩尔)、氨水(0.23克，6.56毫摩尔)和50毫升乙醇，置于100毫升反应瓶中，80℃回流反应，TLC监测反应完毕后，减压脱溶、 柱层析后得到白色固体0.13克。Weigh compound 4.360 (0.15 g, 4.37 mmol), ammonia (0.23 g, 6.56 mmol) and 50 ml of ethanol, put them in a 100 ml reaction flask, and reflux at 80°C for reaction. After the reaction is monitored by TLC, the solution is removed under reduced pressure. , After column chromatography, 0.13 g of white solid is obtained.
实施例9：化合物7.19的制备Example 9: Preparation of Compound 7.19
Figure PCTCN2020073096-appb-000045
Figure PCTCN2020073096-appb-000045
称取化合物4.19(0.50克，2.06毫摩尔)、甲胺盐酸盐(0.69克，10.22毫摩尔)、三乙胺5毫升和40毫升乙醇，置于100毫升反应瓶中，80℃回流反应，TLC监测反应完毕后，减压脱溶、柱层析后得到白色固体0.47克。Weigh compound 4.19 (0.50 g, 2.06 mmol), methylamine hydrochloride (0.69 g, 10.22 mmol), 5 mL of triethylamine and 40 mL of ethanol, place them in a 100 mL reaction flask, and react under reflux at 80°C. After the reaction was monitored by TLC, the solvent was removed under reduced pressure, and 0.47 g of white solid was obtained after column chromatography.
实施例10：化合物7.360的制备Example 10: Preparation of Compound 7.360
Figure PCTCN2020073096-appb-000046
Figure PCTCN2020073096-appb-000046
称取化合物4.360(0.12克，0.52毫摩尔)、甲胺盐酸盐(0.18克，2.67毫摩尔)、三乙胺5毫升和20毫升乙醇，置于50毫升反应瓶中，80℃回流反应，TLC监测反应完毕后，减压脱溶、柱层析后得到白色固体0.11克。Weigh compound 4.360 (0.12 g, 0.52 mmol), methylamine hydrochloride (0.18 g, 2.67 mmol), 5 mL of triethylamine and 20 mL of ethanol, place them in a 50 mL reaction flask, and react under reflux at 80°C. After the reaction was monitored by TLC, the solvent was removed under reduced pressure, and 0.11 g of white solid was obtained after column chromatography.
实施例11：化合物10.19的制备Example 11: Preparation of compound 10.19
Figure PCTCN2020073096-appb-000047
Figure PCTCN2020073096-appb-000047
称取化合物4.19(0.50克，2.06毫摩尔)、甲醇钠(0.56克，10.37毫摩尔)、三乙胺5毫升和25毫升乙醇，置于50毫升反应瓶中，80℃回流反应，TLC监测反应完毕后，减压脱溶、柱层析后得到白色固体0.47克。Weigh compound 4.19 (0.50 g, 2.06 mmol), sodium methoxide (0.56 g, 10.37 mmol), 5 ml of triethylamine and 25 ml of ethanol, place them in a 50 ml reaction flask, and reflux at 80°C for the reaction. TLC monitors the reaction After completion, solvent removal under reduced pressure and column chromatography to obtain 0.47 g of white solid.
实施例12：化合物10.360的制备Example 12: Preparation of compound 10.360
Figure PCTCN2020073096-appb-000048
Figure PCTCN2020073096-appb-000048
称取化合物4.360(0.15克，0.65毫摩尔)、甲醇钠(0.18克，3.33毫摩尔)、三乙胺5毫升和25毫升乙醇，置于50毫升反应瓶中，80℃回流反应，TLC监测反应完毕后，减压脱溶、柱层析后得到白色固体0.14克。Weigh compound 4.360 (0.15 g, 0.65 mmol), sodium methoxide (0.18 g, 3.33 mmol), 5 ml of triethylamine and 25 ml of ethanol, put them in a 50 ml reaction flask, reflux at 80°C for reaction, and monitor the reaction by TLC After completion, solvent removal under reduced pressure, column chromatography to obtain 0.14 g of white solid.
实施例13：化合物12.116的制备Example 13: Preparation of compound 12.116
Figure PCTCN2020073096-appb-000049
Figure PCTCN2020073096-appb-000049
50毫升反应瓶中加入N-甲基苄胺(1.00克，8.26毫摩尔)、乙氧基亚甲基丙二腈(1.01克，8.28毫摩尔)和30毫升乙醇，80℃回流反应，TLC监测反应完毕后，减压蒸除大部分乙醇，冷却、过滤、得到白色固体1.75克。Add N-methylbenzylamine (1.00 g, 8.26 mmol), ethoxymethylene malononitrile (1.01 g, 8.28 mmol) and 30 ml ethanol to a 50 ml reaction flask, and the reaction was refluxed at 80°C, followed by TLC monitoring After the reaction was completed, most of the ethanol was evaporated under reduced pressure, cooled, filtered, and 1.75 g of white solid was obtained.
实施例14：化合物15.360的制备Example 14: Preparation of Compound 15.360
Figure PCTCN2020073096-appb-000050
Figure PCTCN2020073096-appb-000050
100毫升反应瓶中加入N-甲基苄胺(1.00克，8.26毫摩尔)、2-(双(甲硫基)亚甲基)丙二腈(1.50克，8.82毫摩尔)和40毫升甲醇，65℃回流反应，TLC监测反应完毕后，减压蒸除大部分甲醇，冷却、过滤、得到白色固体1.61克。Add N-methylbenzylamine (1.00 g, 8.26 mmol), 2-(bis(methylthio)methylene)malononitrile (1.50 g, 8.82 mmol) and 40 ml methanol into a 100 ml reaction flask, The reaction was refluxed at 65°C. After the reaction was monitored by TLC, most of the methanol was evaporated under reduced pressure, cooled and filtered to obtain 1.61 g of white solid.
实施例15：化合物34.116的制备Example 15: Preparation of compound 34.116
Figure PCTCN2020073096-appb-000051
Figure PCTCN2020073096-appb-000051
称取化合物1.116(0.29克，1.16毫摩尔)、溴乙腈(0.14克，1.18毫摩尔)、氢化钠(0.04克，1.00毫摩尔)和25毫升四氢呋喃，置于50毫升单口瓶中，常温搅拌反应，TLC监测反应完毕后，减压脱溶、柱层析后得到白色固体0.13克。Weigh compound 1.116 (0.29 g, 1.16 mmol), bromoacetonitrile (0.14 g, 1.18 mmol), sodium hydride (0.04 g, 1.00 mmol) and 25 ml of tetrahydrofuran, place them in a 50 ml single-necked flask, and stir to react at room temperature. After the reaction is monitored by TLC, the solvent is removed under reduced pressure, and 0.13 g of white solid is obtained after column chromatography.
实施例16：化合物67.116的制备Example 16: Preparation of Compound 67.116
Figure PCTCN2020073096-appb-000052
Figure PCTCN2020073096-appb-000052
称取化合物1.116(0.38克，1.51毫摩尔)、环丙基甲酰氯(0.16克，1.54毫摩尔)和30毫升甲苯，置于50毫升单口瓶中，110℃回流反应，TLC监测反应完毕后，减压脱溶、柱层析后得到黄色固体0.17克。Weigh compound 1.116 (0.38 g, 1.51 mmol), cyclopropylformyl chloride (0.16 g, 1.54 mmol) and 30 ml of toluene, put them in a 50 ml single-necked flask, and react under reflux at 110°C. After the reaction is monitored by TLC, After solvent removal under reduced pressure and column chromatography, 0.17 g of yellow solid was obtained.
实施例17：化合物89.116的制备Example 17: Preparation of compound 89.116
Figure PCTCN2020073096-appb-000053
Figure PCTCN2020073096-appb-000053
称取化合物1.116(0.45克，1.79毫摩尔)、氯甲酸乙酯(0.20克，1.89毫摩尔)、氢化钠(0.068克，1.70毫摩尔)和25毫升四氢呋喃，置于50毫升单口瓶中，常温搅拌反应，TLC监测反应完毕后，减压脱溶、柱层析后得到黄色固体0.18克。Weigh compound 1.116 (0.45 g, 1.79 mmol), ethyl chloroformate (0.20 g, 1.89 mmol), sodium hydride (0.068 g, 1.70 mmol) and 25 ml of tetrahydrofuran and place them in a 50 ml single-necked flask at room temperature The reaction was stirred and TLC monitored after the reaction was completed, the solution was removed under reduced pressure, and 0.18 g of a yellow solid was obtained after column chromatography.
实施例18：化合物100.7的制备Example 18: Preparation of Compound 100.7
Figure PCTCN2020073096-appb-000054
Figure PCTCN2020073096-appb-000054
50毫升反应瓶中加入4-氟苯胺(1.00克，9.00毫摩尔)、乙氧基亚甲基丙二腈(1.10克，9.01毫摩尔)和30毫升乙醇，80℃回流反应，TLC监测反应完毕后，减压蒸除大部分乙醇，冷却、过滤、得到白色固体1.18克。Add 4-fluoroaniline (1.00 g, 9.00 mmol), ethoxymethylene malononitrile (1.10 g, 9.01 mmol) and 30 ml of ethanol into a 50 ml reaction flask, and react under reflux at 80°C. TLC monitors the completion of the reaction After that, most of the ethanol was evaporated under reduced pressure, cooled and filtered to obtain 1.18 g of white solid.
实施例19：化合物103.360的制备Example 19: Preparation of Compound 103.360
Figure PCTCN2020073096-appb-000055
Figure PCTCN2020073096-appb-000055
100毫升反应瓶中加入苯胺(3.00克，32.24毫摩尔)、2-(双(甲硫基)亚甲基)丙二腈(5.48克，32.24毫摩尔)和50毫升甲醇，65℃回流反应，TLC监测反应完毕后，减压蒸除大部分甲醇，冷却、过滤、得到白色固体4.85克。Add aniline (3.00 g, 32.24 mmol), 2-(bis(methylthio)methylene)malononitrile (5.48 g, 32.24 mmol) and 50 ml methanol into a 100 ml reaction flask, and react at 65°C under reflux. After the reaction was monitored by TLC, most of the methanol was evaporated under reduced pressure, cooled and filtered to obtain 4.85 g of white solid.
实施例20：化合物105.360的制备Example 20: Preparation of compound 105.360
Figure PCTCN2020073096-appb-000056
Figure PCTCN2020073096-appb-000056
称取化合物100.360(1.00克，2.06毫摩尔)、氨水(1.53克，43.66毫摩尔)和30毫升乙醇，置于50毫升反应瓶中，80℃回流反应，TLC监测反应完毕后，减压脱溶、柱层析后得到白色固体0.10克。Weigh compound 100.360 (1.00 g, 2.06 mmol), ammonia (1.53 g, 43.66 mmol) and 30 ml ethanol, put them in a 50 ml reaction flask, reflux the reaction at 80°C, and remove the solvent under reduced pressure after TLC monitoring. After column chromatography, 0.10 g of white solid is obtained.
实施例21：化合物199.4的制备Example 21: Preparation of Compound 199.4
Figure PCTCN2020073096-appb-000057
Figure PCTCN2020073096-appb-000057
称取1-萘胺(2.00克，13.97毫摩尔)、2-(双(甲硫基)亚甲基)丙二腈(0.84克，14.71毫摩尔)、氢化钠(0.84克，21.00毫摩尔)和30毫升四氢呋喃，置于50毫升单口瓶中，65℃回流反应，TLC监测反应完毕后，减压蒸除大部分四氢呋喃，冷却、过滤、得到白色固体3.00克。Weigh out 1-naphthylamine (2.00 g, 13.97 mmol), 2-(bis(methylthio)methylene)malononitrile (0.84 g, 14.71 mmol), sodium hydride (0.84 g, 21.00 mmol) Put 30 ml of tetrahydrofuran and 30 ml of tetrahydrofuran in a 50 ml single-necked flask and react under reflux at 65°C. After the reaction is monitored by TLC, most of the tetrahydrofuran is evaporated under reduced pressure, cooled and filtered to obtain 3.00 g of white solid.
实施例22：化合物211.1的制备Example 22: Preparation of Compound 211.1
Figure PCTCN2020073096-appb-000058
Figure PCTCN2020073096-appb-000058
称取2-氨甲基吡啶(0.30克，2.78毫摩尔)、乙氧基亚甲基丙二腈(0.34克，2.78毫摩尔)和30毫升乙醇，置于50毫升单口瓶中，80℃回流反应，TLC监测反应完毕后，减压蒸除大部分乙醇，冷却、过滤、得到棕色固体0.51克。Weigh 2-aminomethylpyridine (0.30 g, 2.78 mmol), ethoxymethylene malononitrile (0.34 g, 2.78 mmol) and 30 ml ethanol, put them in a 50 ml single-neck flask, and reflux at 80°C After the reaction was monitored by TLC, most of the ethanol was evaporated under reduced pressure, cooled, filtered, and 0.51 g of brown solid was obtained.
实施例23：化合物214.1的制备Example 23: Preparation of Compound 214.1
Figure PCTCN2020073096-appb-000059
Figure PCTCN2020073096-appb-000059
50毫升反应瓶中加入2-噻吩甲胺(0.50克，4.42毫摩尔)、乙氧基亚甲基丙二腈(0.54克，4.42毫摩尔)和25毫升乙醇，80℃回流反应，TLC监测反应完毕后，减压蒸除大部分乙醇，冷却、过滤、得到白色固体0.84克。Add 2-theienylmethylamine (0.50 g, 4.42 mmol), ethoxymethylene malononitrile (0.54 g, 4.42 mmol) and 25 ml ethanol to a 50 ml reaction flask. The reaction was refluxed at 80°C and the reaction was monitored by TLC. After completion, most of the ethanol was evaporated under reduced pressure, cooled and filtered to obtain 0.84 g of white solid.
实施例24：化合物218.1的制备Example 24: Preparation of Compound 218.1
Figure PCTCN2020073096-appb-000060
Figure PCTCN2020073096-appb-000060
50毫升反应瓶中加入3,4-二氯苯乙胺(1.00克，5.29毫摩尔)、乙氧基亚甲基丙二腈(0.65克，5.32毫摩尔)和30毫升乙醇，80℃回流反应，TLC监测反应完毕后，减压蒸除大部分乙醇，冷却、过滤、得到黄色固体1.12克。Add 3,4-dichlorophenethylamine (1.00 g, 5.29 mmol), ethoxymethylene malononitrile (0.65 g, 5.32 mmol) and 30 ml ethanol to a 50 ml reaction flask, and react at 80°C under reflux After the reaction was monitored by TLC, most of the ethanol was evaporated under reduced pressure, cooled and filtered to obtain 1.12 g of yellow solid.
实施例25：化合物218.2的制备Example 25: Preparation of Compound 218.2
Figure PCTCN2020073096-appb-000061
Figure PCTCN2020073096-appb-000061
50毫升反应瓶中加入3-苯基丙-1-胺(1.00克，7.40毫摩尔)、乙氧基亚甲基丙二腈(0.91克，7.45毫摩尔)和30毫升乙醇，80℃回流反应，TLC监测反应完毕后，减压蒸除大部分乙醇，冷却、过滤、得到黄色固体1.17克。Add 3-phenylpropan-1-amine (1.00 g, 7.40 mmol), ethoxymethylene malononitrile (0.91 g, 7.45 mmol) and 30 ml ethanol to a 50 ml reaction flask, and react under reflux at 80°C After the reaction was monitored by TLC, most of the ethanol was evaporated under reduced pressure, cooled and filtered to obtain 1.17 g of yellow solid.
参照以上实施例可以制备本发明通式I中其它化合物。With reference to the above examples, other compounds of the general formula I of the present invention can be prepared.
生物活性测定Biological activity determination
实施例26：对植物细菌病害防治效果的测定Example 26: Determination of the control effect on plant bacterial diseases
用本发明的化合物对多种植物细菌性病害进行了防效测定，针对不同的细菌性病害，试验程序如下：The compound of the present invention has been used for the prevention and control of various plant bacterial diseases. For different bacterial diseases, the test procedure is as follows:
甜瓜果斑病，将待测化合物用少量N,N二甲基甲酰胺溶解，用水稀释至所需要的浓度。将培养至稳定生长期的病原细菌与定量化合物溶液混合均匀，将经过催芽的甜瓜种子放入菌液与化合物的混合液中浸泡半小时，再将种子播种于蚯蚓土培养杯中，放入温室中保湿培养，一般培养两周时间，待对照充分发病后进行防效调查。For melon fruit spot disease, dissolve the test compound with a small amount of N,N dimethylformamide and dilute with water to the required concentration. The pathogenic bacteria cultivated to the stable growth period are mixed with the quantitative compound solution uniformly, the melon seeds that have been germinated are soaked in the mixture of the bacterial solution and the compound for half an hour, and then the seeds are sown in the earthworm soil culture cup and placed in the greenhouse Medium moisturizing culture, usually cultured for two weeks, after the control is fully onset, the control effect investigation will be carried out.
大白菜软腐病，切取2厘米见方的白菜叶片，放入垫有双层滤纸的玻璃培养皿中。将用N，N二甲基甲酰胺溶解，并用水稀释至所需浓度的化合物喷雾于白菜叶片表面，于通风橱内晾干白菜叶片表面药液后，使用接种针在白菜叶片表面针刺造成伤口，将培养至稳定生长期的大白菜软腐病菌取5微升加入伤口内，进行接种。最后将试材放入培养箱中避光培养48小时，待对照充分发病后进行防效调查。For Chinese cabbage soft rot, cut 2 cm square cabbage leaves and put them in a glass petri dish lined with double filter paper. The compound dissolved in N,N dimethylformamide and diluted with water to the required concentration is sprayed on the surface of the cabbage leaves. After drying the liquid on the surface of the cabbage leaves in a fume hood, the inoculation needle is used to acupuncture the surface of the cabbage leaves. In the wound, 5 microliters of soft rot fungus of Chinese cabbage cultivated to a stable growth period is added to the wound for inoculation. Finally, the test materials were placed in an incubator for 48 hours in the dark, and the control effect was investigated after the control fully developed disease.
黄瓜细菌性角斑病、番茄细菌性叶斑病、水稻细菌性条斑病、水稻白叶枯病，将待测化合物用少量N，N二甲基甲酰胺溶解，用水稀释至所需要的浓度。将化合物其喷雾于植物试材表面，于阴凉处风干表面药液后，将培养至稳定生长期的病原细菌菌液喷雾接种于植物试材表面，然后将植物试材放入温室中保湿培养。通常培养十天左右，待对照充分发病后，进行防效调查。Cucumber bacterial angular leaf spot, tomato bacterial leaf spot, rice bacterial leaf spot, rice bacterial leaf blight, dissolve the test compound with a small amount of N,N dimethylformamide, and dilute with water to the required concentration . The compound is sprayed on the surface of the plant test material, the surface drug solution is air-dried in a cool place, and the pathogenic bacteria liquid cultured to a stable growth stage is sprayed on the surface of the plant test material, and then the plant test material is placed in a greenhouse for moisturizing culture. It is usually cultivated for about ten days, and after the control has fully developed disease, the control effect investigation will be conducted.
测试结果如下：The test results are as follows:
600mg/L时，化合物1.1、1.2、1.3、1.4、1.5、1.6、1.7、1.8、1.9、1.19、1.22、1.25、1.36、1.40、1.43、1.45、1.102、1.107、1.116、1.173、1.360、2.8、2.19、2.36、2.116、2.360、4.7、4.8、4.19、4.22、4.36、4.45、4.116、4.173、4.360、6.19、6.36、6.45、6.360、7.19、7.36、7.360、10.19、10.36、10.360、12.116、15.360、34.116、67.116、89.116、100.6、100.7、100.8、100.17、100.19、100.22、100.25、100.36、100.43、100.45、100.107、100.116、100.173、100.360、103.36、103.360、105.360、199.1、199.4、211.1、212.1、214.1、215.1、216.1、218.1、218.2对甜瓜果斑病的防效为100％。At 600mg/L, compounds 1.1, 1.2, 1.3, 1.4, 1.5, 1.6, 1.7, 1.8, 1.9, 1.19, 1.22, 1.25, 1.36, 1.40, 1.43, 1.45, 1.102, 1.107, 1.116, 1.173, 1.360, 2.8, 2.19, 2.36, 2.116, 2.360, 4.7, 4.8, 4.19, 4.22, 4.36, 4.45, 4.116, 4.173, 4.360, 6.19, 6.36, 6.45, 6.360, 7.19, 7.36, 7.360, 10.19, 10.36, 10.360, 12.116, 15.360, 34.116, 67.116, 89.116, 100.6, 100.7, 100.8, 100.17, 100.19, 100.22, 100.25, 100.36, 100.43, 100.45, 100.107, 100.116, 100.173, 100.360, 103.36, 103.360, 105.360, 199.1, 199.4, 211.1, 212.1, 214.1, The control effect of 215.1, 216.1, 218.1, 218.2 on melon fruit spot disease was 100%.
400mg/L时，化合物1.1、1.2、1.3、1.4、1.5、1.6、1.7、1.8、1.9、1.19、1.22、 1.25、1.36、1.40、1.43、1.45、1.102、1.107、1.116、1.173、1.360、2.8、2.19、2.36、2.116、2.360、4.7、4.8、4.19、4.22、4.36、4.45、4.116、4.173、4.360、6.19、6.36、6.45、6.360、7.19、7.36、7.360、10.19、10.36、10.360、12.116、15.360、34.116、67.116、89.116、100.6、100.7、100.8、100.17、100.19、100.22、100.25、100.36、100.43、100.45、100.107、100.116、100.173、100.360、103.36、103.360、105.360、199.1、199.4、211.1、212.1、214.1、215.1、216.1、218.1、218.2对黄瓜细菌性角斑病、水稻细菌性条斑病或水稻白叶枯病的防效为100％。At 400 mg/L, compounds 1.1, 1.2, 1.3, 1.4, 1.5, 1.6, 1.7, 1.8, 1.9, 1.19, 1.22, 1.25, 1.36, 1.40, 1.43, 1.45, 1.102, 1.107, 1.116, 1.173, 1.360, 2.8, 2.19, 2.36, 2.116, 2.360, 4.7, 4.8, 4.19, 4.22, 4.36, 4.45, 4.116, 4.173, 4.360, 6.19, 6.36, 6.45, 6.360, 7.19, 7.36, 7.360, 10.19, 10.36, 10.360, 12.116, 15.360, 34.116, 67.116, 89.116, 100.6, 100.7, 100.8, 100.17, 100.19, 100.22, 100.25, 100.36, 100.43, 100.45, 100.107, 100.116, 100.173, 100.360, 103.36, 103.360, 105.360, 199.1, 199.4, 211.1, 212.1, 214.1, The control effect of 215.1, 216.1, 218.1, 218.2 on cucumber bacterial angular leaf spot, rice bacterial leaf streak or rice bacterial leaf blight is 100%.
400mg/L时，化合物1.1、1.2、1.3、1.4、1.5、1.6、1.7、1.8、1.9、1.19、1.22、1.25、1.36、1.40、1.43、1.45、1.102、1.107、1.116、1.173、1.360、2.8、2.19、2.36、2.116、2.360、4.7、4.8、4.19、4.22、4.36、4.45、4.116、4.173、4.360、6.19、6.36、6.45、6.360、7.19、7.36、7.360、10.19、10.36、10.360、12.116、15.360、34.116、67.116、89.116、100.6、100.7、100.8、100.17、100.19、100.22、100.25、100.36、100.43、100.45、100.107、100.116、100.173、100.360、103.36、103.360、105.360、199.1、199.4、211.1、212.1、214.1、215.1、216.1、218.1、218.2对大白菜软腐病和番茄细菌性叶斑病的防效为100％。At 400 mg/L, compounds 1.1, 1.2, 1.3, 1.4, 1.5, 1.6, 1.7, 1.8, 1.9, 1.19, 1.22, 1.25, 1.36, 1.40, 1.43, 1.45, 1.102, 1.107, 1.116, 1.173, 1.360, 2.8, 2.19, 2.36, 2.116, 2.360, 4.7, 4.8, 4.19, 4.22, 4.36, 4.45, 4.116, 4.173, 4.360, 6.19, 6.36, 6.45, 6.360, 7.19, 7.36, 7.360, 10.19, 10.36, 10.360, 12.116, 15.360, 34.116, 67.116, 89.116, 100.6, 100.7, 100.8, 100.17, 100.19, 100.22, 100.25, 100.36, 100.43, 100.45, 100.107, 100.116, 100.173, 100.360, 103.36, 103.360, 105.360, 199.1, 199.4, 211.1, 212.1, 214.1, The control effect of 215.1, 216.1, 218.1, 218.2 on Chinese cabbage soft rot and tomato bacterial leaf spot is 100%.

Claims (6)

  1. 一种丙二腈类化合物作为杀细菌剂的应用，其特征在于，丙二腈类化合物作为杀细菌剂的应用；其中，丙二腈类化合物结构如通式I所示：An application of a malononitrile compound as a bactericide is characterized by the application of a malononitrile compound as a bactericide; wherein the structure of the malononitrile compound is shown in general formula I:
    Figure PCTCN2020073096-appb-100001
    Figure PCTCN2020073096-appb-100001
    式中：Where:
    n选自0、1、2或3；n is selected from 0, 1, 2 or 3;
    W选自W 1-W 10所示基团之一： W is selected from one of the groups represented by W 1 -W 10 :
    Figure PCTCN2020073096-appb-100002
    Figure PCTCN2020073096-appb-100002
    X 1、X 2、X 3、X 4、X 5各自独立地选自氢、卤素、氰基、硝基、羟基、巯基、氨基、羧基、C 1-C 6烷基、卤代C 1-C 6烷基、C 1-C 6烷氧基、卤代C 1-C 6烷氧基、C 1-C 6烷硫基、卤代C 1-C 6烷硫基、C 1-C 6烷基氨基、C 1-C 6二烷基氨基、C 1-C 6烷基羰基、C 1-C 6烷氧基羰基、-NHCH＝C(CN) 2或-CH 2NHCH＝C(CN) 2； X 1 , X 2 , X 3 , X 4 , and X 5 are each independently selected from hydrogen, halogen, cyano, nitro, hydroxyl, mercapto, amino, carboxy, C 1 -C 6 alkyl, halogenated C 1- C 6 alkyl, C 1 -C 6 alkoxy, halogenated C 1 -C 6 alkoxy, C 1 -C 6 alkylthio, halogenated C 1 -C 6 alkylthio, C 1 -C 6 Alkylamino, C 1 -C 6 dialkylamino, C 1 -C 6 alkylcarbonyl, C 1 -C 6 alkoxycarbonyl, -NHCH=C(CN) 2 or -CH 2 NHCH=C(CN ) 2 ;
    Y 1、Y 2、Y 3、Y 4各自独立地选自氢、卤素、氰基、C 1-C 6烷基、卤代C 1-C 6烷基、C 1-C 6烷氧基、卤代C 1-C 6烷氧基、C 1-C 6烷硫基或卤代C 1-C 6烷硫基； Y 1 , Y 2 , Y 3 , and Y 4 are each independently selected from hydrogen, halogen, cyano, C 1 -C 6 alkyl, halo C 1 -C 6 alkyl, C 1 -C 6 alkoxy, Halogenated C 1 -C 6 alkoxy, C 1 -C 6 alkylthio or halogenated C 1 -C 6 alkylthio;
    Z 1、Z 2、Z 3、Z 4、Z 5、Z 6、Z 7各自独立地选自氢、卤素或C 1-C 6烷基； Z 1 , Z 2 , Z 3 , Z 4 , Z 5 , Z 6 , and Z 7 are each independently selected from hydrogen, halogen or C 1 -C 6 alkyl;
    R 1选自氢、羟基、巯基、氨基、氰基、C 1-C 6烷基、C 1-C 6烷氧基、卤代C 1-C 6烷氧基、C 1-C 6烷硫基、卤代C 1-C 6烷硫基、C 1-C 6烷基氨基或C 1-C 6二烷基氨基； R 1 is selected from hydrogen, hydroxyl, mercapto, amino, cyano, C 1 -C 6 alkyl, C 1 -C 6 alkoxy, halogenated C 1 -C 6 alkoxy, C 1 -C 6 alkyl sulfide Group, halogenated C 1 -C 6 alkylthio, C 1 -C 6 alkylamino or C 1 -C 6 dialkylamino;
    R 2选自氢、C 1-C 6烷基、卤代C 1-C 6烷基、氰基C 1-C 6烷基、C 1-C 6烷基羰基、C 3-C 6环烷基羰基或C 1-C 6烷氧基羰基； R 2 is selected from hydrogen, C 1 -C 6 alkyl, halogenated C 1 -C 6 alkyl, cyano C 1 -C 6 alkyl, C 1 -C 6 alkylcarbonyl, C 3 -C 6 cycloalkane Carbonyl or C 1 -C 6 alkoxycarbonyl;
    或通式I化合物的盐。Or the salt of the compound of formula I.
  2. 根据权利要求1所述的丙二腈类化合物作为杀细菌剂的应用，其特征在于，所述化合物通式I中，The use of the malononitrile compound as a bactericide according to claim 1, characterized in that, in the general formula I,
    n选自0或1；n is selected from 0 or 1;
    W选自W 1-W 10所示基团之一： W is selected from one of the groups represented by W 1 -W 10 :
    X 1、X 2、X 3、X 4、X 5各自独立地选自氢、卤素、氰基、硝基、羟基、巯基、氨基、羧基、C 1-C 4烷基、卤代C 1-C 4烷基、C 1-C 4烷氧基、卤代C 1-C 4烷氧基、C 1-C 4烷硫基、卤代C 1-C 4烷硫基、C 1-C 4烷基氨基、C 1-C 4二烷基氨基、C 1-C 4烷基羰基、C 1-C 4烷氧基羰基、-NHCH＝C(CN) 2或-CH 2NHCH＝C(CN) 2； X 1 , X 2 , X 3 , X 4 , and X 5 are each independently selected from hydrogen, halogen, cyano, nitro, hydroxyl, mercapto, amino, carboxy, C 1 -C 4 alkyl, halogenated C 1- C 4 alkyl, C 1 -C 4 alkoxy, halogenated C 1 -C 4 alkoxy, C 1 -C 4 alkylthio, halogenated C 1 -C 4 alkylthio, C 1 -C 4 Alkylamino, C 1 -C 4 dialkylamino, C 1 -C 4 alkylcarbonyl, C 1 -C 4 alkoxycarbonyl, -NHCH=C(CN) 2 or -CH 2 NHCH=C(CN ) 2 ;
    Y 1、Y 2、Y 3、Y 4各自独立地选自氢、卤素、氰基、C 1-C 4烷基、卤代C 1-C 4烷基、C 1-C 4烷氧基、卤代C 1-C 4烷氧基、C 1-C 4烷硫基或卤代C 1-C 4烷硫基； Y 1 , Y 2 , Y 3 , and Y 4 are each independently selected from hydrogen, halogen, cyano, C 1 -C 4 alkyl, halo C 1 -C 4 alkyl, C 1 -C 4 alkoxy, Halogenated C 1 -C 4 alkoxy, C 1 -C 4 alkylthio or halogenated C 1 -C 4 alkylthio;
    Z 1、Z 2、Z 3、Z 4、Z 5、Z 6、Z 7各自独立地选自氢、卤素或C 1-C 4烷基； Z 1 , Z 2 , Z 3 , Z 4 , Z 5 , Z 6 , and Z 7 are each independently selected from hydrogen, halogen or C 1 -C 4 alkyl;
    R 1选自氢、羟基、巯基、氨基、氰基、C 1-C 4烷基、C 1-C 4烷氧基、卤代C 1-C 4烷氧基、C 1-C 4烷硫基、卤代C 1-C 4烷硫基、C 1-C 4烷基氨基或C 1-C 4二烷基氨基； R 1 is selected from hydrogen, hydroxyl, mercapto, amino, cyano, C 1 -C 4 alkyl, C 1 -C 4 alkoxy, halogenated C 1 -C 4 alkoxy, C 1 -C 4 alkyl sulfide Group, halogenated C 1 -C 4 alkylthio, C 1 -C 4 alkylamino or C 1 -C 4 dialkylamino;
    R 2选自氢、C 1-C 4烷基、卤代C 1-C 4烷基、氰基C 1-C 4烷基、C 1-C 4烷基羰基、C 3-C 6环烷基羰基或C 1-C 4烷氧基羰基； R 2 is selected from hydrogen, C 1 -C 4 alkyl, halogenated C 1 -C 4 alkyl, cyano C 1 -C 4 alkyl, C 1 -C 4 alkylcarbonyl, C 3 -C 6 cycloalkane Carbonyl or C 1 -C 4 alkoxycarbonyl;
    或通式I化合物与盐酸、氢溴酸、硫酸、磷酸、甲酸、乙酸、丙酸、丁酸、戊酸、三氟乙酸、草酸、丙二酸、甲磺酸、4-甲苯磺酸、苹果酸、富马酸、乳酸、马来酸、水杨酸、酒石酸或柠檬酸形成的盐。Or a compound of general formula I and hydrochloric acid, hydrobromic acid, sulfuric acid, phosphoric acid, formic acid, acetic acid, propionic acid, butyric acid, valeric acid, trifluoroacetic acid, oxalic acid, malonic acid, methanesulfonic acid, 4-toluenesulfonic acid, apple Salts of acid, fumaric acid, lactic acid, maleic acid, salicylic acid, tartaric acid or citric acid.
  3. 根据权利要求2所述的丙二腈类化合物作为杀细菌剂的应用，其特征在于，所述化合物通式I中，The use of the malononitrile compound as a bactericide according to claim 2, characterized in that, in the general formula I,
    n选自0或1；n is selected from 0 or 1;
    W选自W 1-W 10所示基团之一： W is selected from one of the groups represented by W 1 -W 10 :
    X 1、X 2、X 3、X 4、X 5各自独立地选自氢、氟、氯、溴、氰基、硝基、羟基、巯基、氨基、羧基、甲基、乙基、正丙基、异丙基、正丁基、异丁基、仲丁基、叔丁基、一氯甲基、二氯甲基、三氯甲基、一溴甲基、二溴甲基、三溴甲基、一氟甲基、二氟甲基、三氟甲基、2,2,2-三氟乙基、七氟异丙基、甲氧基、乙氧基、正丙氧基、异丙氧基、二氟甲氧基、三氟甲氧基、甲硫基、乙硫基、三氟甲硫基、2,2,2-三氟乙硫基、甲氨基、乙氨基、N,N-二甲基氨基、-NHCH＝C(CN) 2或-CH 2NHCH＝C(CN) 2； X 1 , X 2 , X 3 , X 4 , and X 5 are each independently selected from hydrogen, fluorine, chlorine, bromine, cyano, nitro, hydroxyl, mercapto, amino, carboxy, methyl, ethyl, n-propyl , Isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, monochloromethyl, dichloromethyl, trichloromethyl, monobromomethyl, dibromomethyl, tribromomethyl , Monofluoromethyl, difluoromethyl, trifluoromethyl, 2,2,2-trifluoroethyl, heptafluoroisopropyl, methoxy, ethoxy, n-propoxy, isopropoxy , Difluoromethoxy, trifluoromethoxy, methylthio, ethylthio, trifluoromethylthio, 2,2,2-trifluoroethylthio, methylamino, ethylamino, N,N-di Methylamino, -NHCH=C(CN) 2 or -CH 2 NHCH=C(CN) 2 ;
    Y 1、Y 2、Y 3、Y 4各自独立地选自氢、氟、氯、溴、氰基、甲基、乙基、正丙基、异丙基、正丁基、异丁基、仲丁基、叔丁基、一氯甲基、二氯甲基、三氯甲基、一溴甲基、二溴甲基、三溴甲基、一氟甲基、二氟甲基、三氟甲基、2,2,2-三氟乙基、七氟异丙基、甲氧基、乙氧基、正丙氧基、异丙氧基、二氟甲氧基、三氟甲氧基、甲硫基、乙硫基、三氟甲硫基或2,2,2-三氟乙硫基； Y 1 , Y 2 , Y 3 , and Y 4 are each independently selected from hydrogen, fluorine, chlorine, bromine, cyano, methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec Butyl, tert-butyl, monochloromethyl, dichloromethyl, trichloromethyl, monobromomethyl, dibromomethyl, tribromomethyl, monofluoromethyl, difluoromethyl, trifluoromethyl Group, 2,2,2-trifluoroethyl, heptafluoroisopropyl, methoxy, ethoxy, n-propoxy, isopropoxy, difluoromethoxy, trifluoromethoxy, methyl Thio, ethylthio, trifluoromethylthio or 2,2,2-trifluoroethylthio;
    Z 1、Z 2、Z 3、Z 4、Z 5、Z 6、Z 7各自独立地选自氢、氟、氯、溴、甲基、乙基、正丙基、异丙基、正丁基、异丁基、仲丁基或叔丁基； Z 1 , Z 2 , Z 3 , Z 4 , Z 5 , Z 6 , and Z 7 are each independently selected from hydrogen, fluorine, chlorine, bromine, methyl, ethyl, n-propyl, isopropyl, n-butyl , Isobutyl, sec-butyl or tert-butyl;
    R 1选自氢、羟基、巯基、氨基、氰基、甲基、乙基、正丙基、正丁基、甲氧基、乙氧基、正丙氧基、异丙氧基、正丁氧基、甲硫基、乙硫基、正丙硫基、正丁硫基、甲氨基、乙氨基、正丙氨基或正丁氨基； R 1 is selected from hydrogen, hydroxyl, mercapto, amino, cyano, methyl, ethyl, n-propyl, n-butyl, methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy Group, methylthio, ethylthio, n-propylthio, n-butylthio, methylamino, ethylamino, n-propylamino or n-butylamino;
    R 2选自氢、甲基、乙基、正丙基、异丙基、正丁基、异丁基、仲丁基、叔丁基、氰甲基、2,2,2-三氟乙基、乙酰基、正丙酰基、环丙基甲酰基、甲氧基羰基、乙氧基羰基、正丙氧基羰基或正丁氧基羰基； R 2 is selected from hydrogen, methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, cyanomethyl, 2,2,2-trifluoroethyl , Acetyl, n-propionyl, cyclopropylformyl, methoxycarbonyl, ethoxycarbonyl, n-propoxycarbonyl or n-butoxycarbonyl;
    或通式I化合物与盐酸、氢溴酸、硫酸、磷酸、甲酸、乙酸、丙酸、丁酸、戊酸、三氟乙酸、草酸、丙二酸、甲磺酸、4-甲苯磺酸、苹果酸、富马酸、乳酸、马来酸、水杨酸、酒石酸或柠檬酸形成的盐。Or a compound of general formula I and hydrochloric acid, hydrobromic acid, sulfuric acid, phosphoric acid, formic acid, acetic acid, propionic acid, butyric acid, valeric acid, trifluoroacetic acid, oxalic acid, malonic acid, methanesulfonic acid, 4-toluenesulfonic acid, apple Salts of acid, fumaric acid, lactic acid, maleic acid, salicylic acid, tartaric acid or citric acid.
  4. 根据权利要求3所述的丙二腈类化合物作为杀细菌剂的应用，其特征在于，所述化合物通式I中，The use of the malononitrile compound as a bactericide according to claim 3, characterized in that, in the general formula I,
    n选自0或1；n is selected from 0 or 1;
    W选自W 1-W 10所示基团之一： W is selected from one of the groups represented by W 1 -W 10 :
    X 1、X 2、X 3、X 4、X 5各自独立地选自氢、氟、氯、溴、氰基、硝基、羟基、巯基、氨基、羧基、甲基、乙基、正丙基、异丙基、正丁基、异丁基、仲丁基、叔丁基、三氟 甲基、甲氧基、乙氧基、三氟甲氧基、甲硫基、甲氨基、N,N-二甲基氨基、-NHCH＝C(CN) 2或-CH 2NHCH＝C(CN) 2； X 1 , X 2 , X 3 , X 4 , and X 5 are each independently selected from hydrogen, fluorine, chlorine, bromine, cyano, nitro, hydroxyl, mercapto, amino, carboxy, methyl, ethyl, n-propyl , Isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, trifluoromethyl, methoxy, ethoxy, trifluoromethoxy, methylthio, methylamino, N, N -Dimethylamino, -NHCH=C(CN) 2 or -CH 2 NHCH=C(CN) 2 ;
    Y 1、Y 2、Y 3、Y 4选自氢； Y 1 , Y 2 , Y 3 , and Y 4 are selected from hydrogen;
    Z 1、Z 2、Z 3、Z 4、Z 5、Z 6、Z 7选自氢； Z 1 , Z 2 , Z 3 , Z 4 , Z 5 , Z 6 , and Z 7 are selected from hydrogen;
    R 1选自氢、氨基、甲基、甲氧基、乙氧基、甲硫基、乙硫基、甲氨基或乙氨基； R 1 is selected from hydrogen, amino, methyl, methoxy, ethoxy, methylthio, ethylthio, methylamino or ethylamino;
    R 2选自氢、甲基、乙基、2,2,2-三氟乙基、氰甲基、乙酰基、正丙酰基、环丙基甲酰基、甲氧基羰基或乙氧基羰基； R 2 is selected from hydrogen, methyl, ethyl, 2,2,2-trifluoroethyl, cyanomethyl, acetyl, n-propionyl, cyclopropylformyl, methoxycarbonyl or ethoxycarbonyl;
    或通式I化合物与盐酸、氢溴酸、硫酸、磷酸、甲酸、乙酸、丙酸、丁酸、戊酸、三氟乙酸、草酸、丙二酸、甲磺酸、4-甲苯磺酸、苹果酸、富马酸、乳酸、马来酸、水杨酸、酒石酸或柠檬酸形成的盐。Or a compound of general formula I and hydrochloric acid, hydrobromic acid, sulfuric acid, phosphoric acid, formic acid, acetic acid, propionic acid, butyric acid, valeric acid, trifluoroacetic acid, oxalic acid, malonic acid, methanesulfonic acid, 4-toluenesulfonic acid, apple Salts of acid, fumaric acid, lactic acid, maleic acid, salicylic acid, tartaric acid or citric acid.
  5. 根据权利要求1-4任意一项所述的丙二腈类化合物作为杀细菌剂的应用，其特征在于：所述通式I所示的化合物在作为用于控制植物细菌性病害中的应用。The use of the malononitrile compound as a bactericide according to any one of claims 1 to 4, characterized in that the compound represented by the general formula I is used as an application for controlling plant bacterial diseases.
  6. 根据权利要求5所述的丙二腈类化合物作为杀细菌剂的应用，其特征在于：所述植物细菌性病害为果斑病、叶斑病、青枯病、细菌性疫病、溃疡病、软腐病、细菌性角斑病、细菌性条斑病、叶枯病、白叶枯病、野火病或细菌性疮痂病。The use of the malononitrile compound as a bactericide according to claim 5, characterized in that: the plant bacterial disease is fruit spot, leaf spot, bacterial wilt, bacterial blight, ulcer, soft Rot, bacterial angular leaf spot, bacterial leaf spot, leaf blight, bacterial leaf blight, wildfire or bacterial scab.
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