CN110396083B - Pyridazinonyl-contained butenolide compound and application thereof - Google Patents

Pyridazinonyl-contained butenolide compound and application thereof Download PDF

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CN110396083B
CN110396083B CN201810373876.9A CN201810373876A CN110396083B CN 110396083 B CN110396083 B CN 110396083B CN 201810373876 A CN201810373876 A CN 201810373876A CN 110396083 B CN110396083 B CN 110396083B
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关爱莹
王明安
孙芹
杨金龙
赵宇
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Shenyang Sinochem Agrochemicals R&D Co Ltd
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    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
    • A01N43/00—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds
    • A01N43/48—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with two nitrogen atoms as the only ring hetero atoms
    • A01N43/58—1,2-Diazines; Hydrogenated 1,2-diazines
    • 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
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    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
    • C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
    • C07D405/12—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a chain containing hetero atoms as chain links
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
    • C07D405/14—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing three or more hetero rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
    • C07D417/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing three or more hetero rings

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Abstract

The invention belongs to the field of chemistry, and particularly relates to a compound containing pyridazinone-group butenolide and a structural formula of a compound using the same, wherein the structural formula is shown as a general formula I, and definitions of all substituents in the formula are shown in an instruction. The compounds of the general formula I show excellent activity on various pathogenic bacteria in the agricultural or other fields, and can be advantageously used for protecting crops, livestock and livestock which are important in the agricultural and horticultural industries and the environment where human beings are frequently used from the harmful bacteria.

Description

Pyridazinonyl-contained butenolide compound and application thereof
Technical Field
The invention belongs to the field of chemistry, and particularly relates to a compound containing pyridazinone-group butenolide and application thereof.
Background
Patent CN104370891 discloses that 5- (butenolide-3-ethylidene) -2-aminoimidazolidinone compounds represented by the following general formula TB have good bactericidal effects on various plant pathogenic bacteria such as rice sheath blight disease, sclerotinia rot of colza and phytophthora capsici.
Figure BDA0001638987870000011
Patent WO 9619469 discloses 4-substituted phenylbutenolide compounds represented by the following general formula for use in treatment of cyclooxygenase-2 mediated diseases.
Figure BDA0001638987870000012
(Y may be selected from O; R)5R6Either O or S)
However, the compounds containing pyridazinone-group butenolide, the structures of which are shown in the general formula I, are not reported.
Disclosure of Invention
The invention aims to provide a pyridazinone-containing butenolide compound capable of controlling various pathogenic bacteria and application thereof in preparing medicines for preventing and treating pathogenic bacteria in agriculture or other fields.
In order to achieve the purpose, the technical scheme of the invention is as follows:
the invention provides a butenolide compound, which is a compound shown as a general formula I,
Figure BDA0001638987870000013
Figure BDA0001638987870000021
in the formula:
R1selected from hydrogen, C1-C12Alkyl, benzyl, substituted by 1-5R9Substituted benzyl, heteroarylmethyl or substituted by 1-5R9Substituted heteroarylmethyl;
R2selected from hydrogen or halogen;
R3selected from hydrogen, benzyl or substituted by 1-5R9A substituted benzyl group;
R4、R5each independently selected from hydrogen, cyano or C1-C12An alkyl group;
R6selected from hydrogen, C1-C12Alkyl radical, C1-C12Cycloalkyl, unsubstituted or substituted by 1-5R9Substituted aryl or heteroaryl;
R7、R8each independently selected from hydrogen or C1-C12An alkyl group;
R7and R8Can also form a ternary, quaternary, quinary, hexahydric, heptatomic or octatomic ring containing C, N, O or S together with the connected carbon atoms;
x is selected from NR10O or S;
R9selected from halogen, hydroxy, amino, cyano, nitro, C1-C12Alkyl, halo C1-C12Alkyl, aryl, heteroaryl, and heteroaryl,C1-C12Alkoxy, halo C1-C12Alkoxy radical, C3-C12Cycloalkyl radical, C1-C12Alkylamino, halogeno C1-C12Alkylamino radical, di (C)1-C12Alkyl) amino, halo-di (C)1-C12Alkyl) amino, C (═ O) NR11R12、C1-C12Alkylthio, halo C1-C12Alkylthio radical, C2-C12Alkenyl radical, C2-C12Alkynyl, C2-C12Alkenyloxy, halogeno C2-C12Alkenyloxy radical, C2-C12Alkynyloxy, halo C2-C12Alkynyloxy, C1-C12Alkylsulfonyl, halo C1-C12Alkylsulfonyl radical, C1-C12Alkylcarbonyl, halo C1-C12Alkylcarbonyl group, C1-C12Alkoxycarbonyl, halo C1-C12Alkoxycarbonyl group, C1-C12Alkoxy radical C1-C12Alkyl, halo C1-C12Alkoxy radical C1-C12Alkyl radical, C1-C12Alkylthio group C1-C12Alkyl, halo C1-C12Alkylthio group C1-C12Alkyl radical, C1-C12Alkoxycarbonyl radical C1-C12Alkyl, halo C1-C12Alkoxycarbonyl radical C1-C12Alkyl radical, C1-C12Alkylthio carbonyl group C1-C12Alkyl, halo C1-C12Alkylthio carbonyl group C1-C12Alkyl radical, C1-C12Alkylcarbonyloxy, halo C1-C12Alkylcarbonyloxy, C1-C12Alkoxycarbonyloxy, halo C1-C12Alkoxycarbonyloxy, C1-C12Alkylsulfonyloxy, halo C1-C12Alkylsulfonyloxy, C1-C12Alkoxy radical C1-C12Alkoxy or halo C1-C12Alkoxy radical C1-C12An alkoxy group;
R11、R12same or different are respectively selected from hydrogen and C1-C12Alkyl or halo C1-C12An alkyl group;
R10selected from hydrogen, hydroxy, formyl, C1-C12Alkyl, halo C1-C12Alkyl radical, C1-C12Alkoxy, halo C1-C12Alkoxy radical, C3-C12Cycloalkyl radical, C1-C12Alkylthio radical, C2-C12Alkenyl radical, C2-C12Alkynyl, halo C2-C12Alkenyl, halo C2-C12Alkynyl, C1-C12Alkoxy radical C1-C12Alkyl, halo C1-C12Alkoxy radical C1-C12Alkyl radical, C1-C12Alkylthio group C1-C12Alkyl, halo C1-C12Alkylthio group C1-C12Alkyl radical, C1-C12Alkylsulfinyl, halogeno C1-C12Alkylsulfinyl radical, C1-C12Alkylsulfonyl, halo C1-C12Alkylsulfonyl radical, C1-C12Alkylaminosulfonyl, di (C)1-C12Alkyl) aminosulfonyl, C1-C12Alkylsulfonylaminocarbonyl group, C1-C12Alkylcarbonylaminosulfonyl radical, C3-C12Cycloalkyloxycarbonyl radical, C1-C12Alkylcarbonyl, halo C1-C12Alkylcarbonyl group, C1-C12Alkoxycarbonyl, halo C1-C12Alkoxycarbonyl group, C1-C12Alkyl carbonyl radical C1-C12Alkyl radical, C1-C12Alkoxycarbonyl radical C1-C12Alkyl radical, C1-C12Alkylaminocarbonyl, di (C)1-C12Alkyl) aminocarbonyl, C2-C12Alkenyloxycarbonyl radical, C2-C12AlkynyloxycarbonylBase, C1-C12Alkoxy radical C1-C12Alkoxycarbonyl group, C1-C12Alkylaminosulfur or di (C)1-C12Alkyl) aminosulfanyl.
Preferably, in the compound of formula I:
R1selected from hydrogen, C1-C6Alkyl, benzyl, substituted by 1-4R9Substituted benzyl, pyridylmethyl, substituted by 1-4R9Substituted pyridylmethyl, thiazolylmethyl or substituted with 1-4R9Substituted thiazolylmethyl;
R2selected from hydrogen or halogen;
R3selected from hydrogen, benzyl or substituted by 1-4R9A substituted benzyl group;
R4、R5each independently selected from hydrogen, cyano or C1-C6An alkyl group;
R6selected from hydrogen, C1-C6Alkyl radical, C1-C6Cycloalkyl, unsubstituted or substituted by 1-4R9Substituted aryl or heteroaryl;
R7、R8each independently selected from hydrogen or C1-C6An alkyl group;
R7and R8Can also form a ternary, quaternary, quinary, hexahydric, heptatomic or octatomic ring containing C, N, O or S together with the connected carbon atoms;
x is selected from NR10O or S;
R9selected from halogen, hydroxy, amino, cyano, nitro, C1-C6Alkyl, halo C1-C6Alkyl radical, C1-C6Alkoxy, halo C1-C6Alkoxy radical, C3-C8Cycloalkyl, C1-C6Alkylamino, halogeno C1-C6Alkylamino radical, di (C)1-C6Alkyl) amino, halo-di (C)1-C6Alkyl) amino, C (═ O) NR11R12、C1-C6Alkylthio, halo C1-C6Alkylthio group、C2-C8Alkenyl radical, C2-C8Alkynyl, C2-C8Alkenyloxy, halogeno C2-C8Alkenyloxy radical, C2-C8Alkynyloxy, halo C2-C8Alkynyloxy, C1-C6Alkylsulfonyl, halo C1-C6Alkylsulfonyl radical, C1-C6Alkylcarbonyl, halo C1-C6Alkylcarbonyl group, C1-C6Alkoxycarbonyl, halo C1-C6Alkoxycarbonyl group, C1-C6Alkoxy radical C1-C6Alkyl, halo C1-C6Alkoxy radical C1-C6Alkyl radical, C1-C6Alkylthio group C1-C6Alkyl, halo C1-C6Alkylthio group C1-C6Alkyl radical, C1-C6Alkoxycarbonyl radical C1-C6Alkyl, halo C1-C6Alkoxycarbonyl radical C1-C6Alkyl radical, C1-C6Alkylthio carbonyl group C1-C6Alkyl, halo C1-C6Alkylthio carbonyl group C1-C6Alkyl radical, C1-C6Alkylcarbonyloxy, halo C1-C6Alkylcarbonyloxy, C1-C6Alkoxycarbonyloxy, halo C1-C6Alkoxycarbonyloxy, C1-C6Alkylsulfonyloxy, halo C1-C6Alkylsulfonyloxy, C1-C6Alkoxy radical C1-C6Alkoxy or halo C1-C6Alkoxy radical C1-C6An alkoxy group;
R11、R12same or different are respectively selected from hydrogen and C1-C6Alkyl or halo C1-C6An alkyl group;
R10selected from hydrogen, hydroxy, formyl, C1-C6Alkyl, halo C1-C6Alkyl radical, C1-C6Alkoxy, halo C1-C6Alkoxy radical,C3-C8Cycloalkyl radical, C1-C6Alkylthio radical, C2-C8Alkenyl radical, C2-C8Alkynyl, halo C2-C8Alkenyl, halo C2-C8Alkynyl, C1-C6Alkoxy radical C1-C6Alkyl, halo C1-C6Alkoxy radical C1-C6Alkyl radical, C1-C6Alkylthio group C1-C6Alkyl, halo C1-C6Alkylthio group C1-C6Alkyl radical, C1-C6Alkylsulfinyl, halogeno C1-C6Alkylsulfinyl radical, C1-C6Alkylsulfonyl, halo C1-C6Alkylsulfonyl radical, C1-C6Alkylaminosulfonyl, di (C)1-C6Alkyl) aminosulfonyl, C1-C6Alkylsulfonylaminocarbonyl group, C1-C6Alkylcarbonylaminosulfonyl radical, C3-C6Cycloalkyloxycarbonyl radical, C1-C6Alkylcarbonyl, halo C1-C6Alkylcarbonyl group, C1-C6Alkoxycarbonyl, halo C1-C6Alkoxycarbonyl group, C1-C6Alkyl carbonyl radical C1-C6Alkyl radical, C1-C6Alkoxycarbonyl radical C1-C6Alkyl radical, C1-C6Alkylaminocarbonyl, di (C)1-C6Alkyl) aminocarbonyl, C2-C6Alkenyloxycarbonyl radical, C2-C6Alkynyloxycarbonyl group, C1-C6Alkoxy radical C1-C6Alkoxycarbonyl group, C1-C6Alkylaminosulfenyl or di (C)1-C6Alkyl) aminosulfanyl.
Further preferably, in the compound of formula I:
R1selected from hydrogen, C1-C4Alkyl, benzyl, substituted by 1-3R9Substituted benzyl, pyridylmethyl, substituted by 1-3R9Substituted pyridylmethyl, thiazolylmethyl or substituted by 1 to 3R9Substituted thiazolylmethyl;
R2selected from hydrogen or halogen;
R3selected from hydrogen, benzyl or substituted by 1-3R9A substituted benzyl group;
R4、R5each independently selected from hydrogen, cyano or C1-C4An alkyl group;
R6selected from hydrogen, C1-C4Alkyl radical, C1-C4Cycloalkyl, unsubstituted or substituted by 1-3R9Substituted aryl or heteroaryl;
R7、R8each independently selected from hydrogen or C1-C4An alkyl group;
R7and R8And optionally together with the linking carbon atom to form a saturated five-or six-membered carbocyclic ring;
x is selected from O or S;
R9selected from halogen, hydroxy, amino, cyano, nitro, C1-C4Alkyl, halo C1-C4Alkyl radical, C1-C4Alkoxy, halo C1-C4Alkoxy radical, C3-C6Cycloalkyl radical, C1-C4Alkylamino, halogeno C1-C4Alkylamino radical, di (C)1-C4Alkyl) amino, halo-di (C)1-C4Alkyl) amino, C (═ O) N (CH)3)2、C1-C4Alkylthio, halo C1-C4Alkylthio radical, C1-C4Alkylsulfonyl, halo C1-C4Alkylsulfonyl radical, C1-C4Alkylcarbonyl, halo C1-C4Alkylcarbonyl group, C1-C4Alkoxycarbonyl, halo C1-C4An alkoxycarbonyl group.
Still further preferably, in the compound of formula I:
R1selected from hydrogen, methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, isobutyl, tert-butyl, benzyl, substituted by 1-3R9Substituted benzyl, pyridineRadical methyl radical, by 1-3R9Substituted pyridylmethyl, thiazolylmethyl or substituted by 1 to 3R9Substituted thiazolylmethyl;
R2selected from hydrogen, fluorine, chlorine, bromine or iodine;
R3selected from hydrogen, benzyl or substituted by 1-3R9A substituted benzyl group;
R4、R5each independently selected from hydrogen, cyano, methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, isobutyl or tert-butyl;
R6selected from hydrogen, methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, isobutyl, tert-butyl, cyclopropyl, cyclobutyl, unsubstituted or substituted by 1-3R9Substituted aryl or heteroaryl;
R7、R8each independently selected from hydrogen, methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, isobutyl, tert-butyl, cyclopropyl or cyclobutyl;
R7and R8And optionally together with the linking carbon atom to form a saturated five-or six-membered carbocyclic ring;
x is selected from O or S;
R9selected from halogen, hydroxy, amino, cyano, nitro, C1-C4Alkyl, halo C1-C4Alkyl radical, C1-C4Alkoxy, halo C1-C4Alkoxy radical, C3-C6Cycloalkyl radical, C1-C4Alkylamino, halogeno C1-C4Alkylamino radical, di (C)1-C4Alkyl) amino, halo-di (C)1-C4Alkyl) amino, C (═ O) N (CH)3)2、C1-C4Alkylthio, halo C1-C4Alkylthio radical, C1-C4Alkylsulfonyl, halo C1-C4Alkylsulfonyl radical, C1-C4Alkylcarbonyl, halo C1-C4Alkylcarbonyl group, C1-C4Alkoxycarbonyl, halo C1-C4An alkoxycarbonyl group.
More preferably, in the compounds of formula I:
R1selected from hydrogen, methyl, ethyl, n-propyl, isopropyl, n-butyl, tert-butyl, p-chlorobenzyl, 2-chloropyridine-5-methyl or 2-chlorothiazole 5-methyl;
R2selected from hydrogen, chlorine or bromine;
R3selected from hydrogen;
R4selected from hydrogen or cyano;
R5selected from hydrogen, methyl, ethyl, n-propyl or isopropyl;
R6selected from methyl or phenyl;
R7、R8is selected from methyl;
R7and R8And optionally together with the linking carbon atom to form a saturated five-or six-membered carbocyclic ring;
x is selected from O or S.
In the definitions of the compounds of the general formula I given above, the terms used are generally defined as follows:
halogen: refers to fluorine, chlorine, bromine or iodine. Alkyl groups: straight-chain or branched alkyl groups, such as methyl, ethyl, propyl, isopropyl, n-butyl or tert-butyl. Cycloalkyl: substituted or unsubstituted cyclic alkyl groups, such as cyclopropyl, cyclopentyl or cyclohexyl. Substituents such as methyl, halogen, and the like. Halogenated alkyl groups: straight-chain or branched alkyl groups in which the hydrogen atoms may be partially or completely substituted with halogen atoms, for example, chloromethyl, dichloromethyl, trichloromethyl, fluoromethyl, difluoromethyl, trifluoromethyl and the like. Alkylsulfinyl group: straight or branched chain alkyl groups are attached to the structure via a sulfinyl (-SO-) group, such as methylsulfinyl. Haloalkylsulfinyl group: straight-chain or branched alkylsulfinyl groups in which the hydrogen atoms of the alkyl group may be partially or fully substituted by halogen atoms. Haloalkylsulfonyl group: straight-chain or branched alkylsulfonyl wherein the hydrogen atoms of the alkyl group may be partially or wholly substituted by halogen atoms. Alkylaminosulfenyl: such as CH3NHS-、C2H5NHS-. Dialkylaminosulfenyl: such as (CH)3)2NS-、(C2H5)2NS-. Alkylaminosulfonyl: alkyl-NH-SO2-. Dialkylaminosulfonyl: (alkyl group)2-N-SO2-. Alkylsulfonylaminocarbonyl group: alkyl-SO2-NH-CO-. Alkylcarbonylaminosulfonyl: alkyl-CO-NH-SO2-. Alkylcarbonylalkyl group: alkyl-CO-alkyl-. Alkylsulfonyloxy group: alkyl-S (O)2-O-. Haloalkylsulfonyloxy: the hydrogen atoms of the alkyl group of the alkylsulfonyloxy group may be partially or wholly substituted by halogen atoms, e.g. CF3-SO2-O. Cycloalkyloxycarbonyl group: such as cyclopropyloxycarbonyl, cyclohexyloxycarbonyl, and the like. Alkoxy groups: straight or branched chain alkyl groups attached to the structure via oxygen atom linkages. Haloalkoxy groups: straight-chain or branched alkoxy groups in which the hydrogen atoms may be partially or completely replaced by halogen atoms. For example, chloromethoxy, dichloromethoxy, trichloromethoxy, fluoromethoxy, difluoromethoxy, trifluoromethoxy, chlorofluoromethoxy, trifluoroethoxy and the like. Halogenated alkoxycarbonyl group: the hydrogen atoms of the alkyl group of the alkoxycarbonyl group may be partially or wholly replaced by halogen atoms, e.g. ClCH2CH2OCO-、CF3CH2OCO-, etc. Alkoxyalkyl groups: alkyl-O-alkyl-, e.g. CH3OCH2-. Haloalkoxyalkyl groups: the hydrogen atoms of the alkyl groups of alkoxyalkyl groups may be partially or fully substituted by halogen atoms, e.g. ClCH2CH2OCH2-、CF3CH2OCH2-and the like. Alkoxycarbonylalkyl groups: alkoxycarbonyl-alkyl-, e.g. CH3OCOCH2-. Haloalkoxycarbonylalkyl: the hydrogen atoms of the alkyl group of the alkoxycarbonylalkyl group may be partially or fully substituted by halogen atoms, e.g. CF3CH2OCOCH2-. Alkylcarbonyloxy group: such as CH3COO-, etc. Haloalkylcarbonyloxy: the hydrogen atoms of the alkylcarbonyloxy group may be partially or fully substituted by halogen atoms, e.g. CF3COO-, etc. Alkoxycarbonyloxy: alkoxycarbonyl-oxy-, e.g. CH3OCOO-. Haloalkoxycarbonyl group: the hydrogen atoms of the alkyl group of the alkoxycarbonyloxy group may be partially or wholly substituted by halogen atoms, e.g. CF3OCOO-。Alkylthio-carbonylalkyl: alkylthiocarbonyl-alkyl-, e.g. CH3SCOCH2-. Haloalkylthiocarbonylalkyl: the hydrogen atoms of the alkyl group of the alkylthiocarbonylalkyl group may be partially or wholly substituted by halogen atoms, e.g. CF3CH2SCOCH2-. Alkoxyalkoxy group: such as CH3OCH2O-, etc. Haloalkoxyalkyl: the hydrogen atoms of the alkoxy groups being partially or wholly replaced by halogen atoms, e.g. CF3OCH2O-is formed. Alkoxy alkoxycarbonyl group: such as CH3OCH2CH2OCO-, etc. Alkylthio group: straight or branched chain alkyl groups attached to the structure via a sulfur atom. Haloalkylthio: straight-chain or branched alkylthio groups in which the hydrogen atoms may be partially or wholly replaced by halogen atoms. For example, chloromethylthio, dichloromethylthio, trichloromethylthio, fluoromethylthio, difluoromethylthio, trifluoromethylthio, chlorofluoromethylthio and the like. Alkylthioalkyl: alkyl-S-alkyl-, e.g. CH3SCH2-. Haloalkylthioalkyl: the hydrogen atoms of the alkyl group of an alkylthioalkyl group may be partially or fully substituted by halogen atoms, e.g. ClCH2CH2SCH2-、CF3CH2SCH2-and the like. Alkylamino group: straight or branched chain alkyl, linked to the structure via a nitrogen atom. Haloalkylamino group: straight-chain or branched alkylamino, the hydrogen atoms on these alkyl groups may be partially or completely substituted by halogen atoms. Dialkylamino group: such as (CH)3)2N-，(CH3CH2)2N-is provided. Halogenated dialkylamino group: the hydrogen atoms of the alkyl groups being partially or wholly replaced by halogen atoms, e.g. (CF)3)2N-，(CF3CH2)2N-is provided. Alkenyl: straight-chain or branched alkenes, for example ethenyl, 1-propenyl, 2-propenyl and the different butenyl, pentenyl and hexenyl isomers. Alkenyl also includes polyenes such as 1, 2-allenyl and 2, 4-hexadienyl. Halogenated alkenyl groups: straight-chain or branched alkenes in which the hydrogen atoms may be partially or completely replaced by halogen atoms. Alkenyloxy: linear or branched alkenes linked to the structure via oxygen atoms. Halogenated alkenyloxy group: linear or branched alkenyloxy radicals, in whichThe hydrogen atoms on these alkenyloxy groups may be partially or fully substituted by halogen atoms. Alkenylthio group: linear or branched alkenes linked to the structure via a sulfur atom bond. Such as CH2＝CHCH2S-. Alkenyloxycarbonyl radical: such as CH2＝CHCH2OCO-, etc. Alkynyl: straight-chain or branched alkynes, for example ethynyl, 1-propynyl, 2-propynyl and the different butynyl, pentynyl and hexynyl isomers. Alkynyl also includes groups consisting of multiple triple bonds, such as 2, 5-hexadiynyl. Halogenated alkynyl group: straight-chain or branched alkynes, in which the hydrogen atoms may be partially or completely replaced by halogen atoms. Alkynyloxy: straight or branched alkynes, linked to the structure via oxygen atom bonds. Haloalkynyloxy: straight-chain or branched alkynyloxy, in which the hydrogen atoms may be partially or completely substituted by halogen atoms. Alkynyloxycarbonyl group: such as CH ≡ CCH2OCO-, etc. An alkylsulfonyl group: straight or branched chain alkyl via sulfonyl (-SO)2-) is attached to a structure, such as a methylsulfonyl group. Haloalkylsulfonyl group: straight-chain or branched alkylsulfonyl wherein the hydrogen atoms of the alkyl group may be partially or wholly substituted by halogen atoms. An alkylcarbonyl group: the alkyl radical being bound to the structure via a carbonyl group, e.g. CH3CO-，CH3CH2CO-. Halogenated alkylcarbonyl group: the hydrogen atoms of the alkyl group of the alkylcarbonyl group may be partially or fully substituted by halogen atoms, e.g. CF3CO-. Alkoxycarbonyl group: the alkoxy group is attached to the structure via a carbonyl group. Such as CH3OCO-，CH3CH2OCO-. Aminocarbonyl group: such as NH2CO-. Alkyl amino carbonyl: alkyl-NH-CO-, e.g. CH3NHCO-，CH3CH2NHCO-. Dialkylaminocarbonyl group: such as (CH)3)2NCO-，(CH3CH2)2NCO-. The aryl moiety in (hetero) aryl, (hetero) arylalkyl, (hetero) arylcarbonyl, (hetero) arylmethylcarbonyl, (hetero) arylcarbonylalkyl, (hetero) aryloxycarbonyl, (hetero) arylalkyloxycarbonyl, and the like includes phenyl or naphthyl. Heteroaryl is a five or six membered ring containing 1 or more heteroatoms N, O, S. Such as furyl, pyrazolyl, thiazolyl, pyridyl, pyrimidinyl, pyrazinyl, pyridazinyl, triazinyl, quinolinyl, and the like. (hetero) aryl group: such as phenylAnd the like. (hetero) arylalkyl: such as benzyl, phenethyl, p-chlorobenzyl, 2-chloropyridin-5-yl, 2-chloro-thiazol-5-yl, and the like. (hetero) arylcarbonyl group: such as benzoyl, 4-chlorobenzoyl and the like. (hetero) arylmethylcarbonyl: such as PhCH2CO-. (hetero) arylcarbonylalkyl: such as PhCOCH2-. (hetero) aryloxycarbonyl group: such as phenoxycarbonyl, 4-chlorophenoxycarbonyl, 4-nitrophenoxycarbonyl, naphthyloxycarbonyl, etc. Arylalkyloxycarbonyl group: such as benzyloxycarbonyl, 4-chlorobenzyloxycarbonyl, 4-trifluoromethylbenzyloxycarbonyl and the like. (hetero) arylalkyloxycarbonyl: such as PhCH2OCO-、4-Cl-PhCH2OCO-, etc.
Some of the compounds of the present invention can be illustrated by specific compounds listed in tables 1 to 80, but are not intended to limit the present invention.
Figure BDA0001638987870000061
When R is2＝R3＝R4＝H，R5＝R6＝CH3，R7，R8＝-(CH2)5-, X ═ O, R1The substituents are shown in Table 1, and represent the compound numbers of 1-21 in sequence.
TABLE 1
Figure BDA0001638987870000071
Table 2: in the general formula I, when R2＝Cl，R3＝R4＝H，R5＝R6＝CH3，R7，R8＝-(CH2)5-, X ═ O, substituent R1In accordance with the substituents shown in Table 1, the substituents correspond in turn to 1-1-1-21 of Table 1, and represent compounds numbered in turn 2-1-2-21.
Table 3: in the general formula I, when R2＝Br，R3＝R4＝H，R5＝R6＝CH3，R7，R8＝-(CH2)5-, X ═ O, substituent R1In accordance with the substituents shown in Table 1, the substituents correspond in turn to 1-1-1-21 of Table 1, and represent the compounds having the numbers of 3-1-3-21 in turn.
Table 4: in the general formula I, when R2＝R4＝H，R3＝Ph(CH2)，R5＝R6＝CH3，R7，R8＝-(CH2)5-, X ═ O, substituent R1In accordance with the substituents shown in Table 1, the substituents correspond in turn to 1-1-1-21 of Table 1, and represent the compounds having the numbers of 4-1-4-21 in turn.
Table 5: in the general formula I, when R2＝Cl，R3＝Ph(CH2)，R4＝H，R5＝R6＝CH3，R7，R8＝-(CH2)5-, X ═ O, substituent R1In accordance with the substituents shown in Table 1, the substituents correspond in turn to 1-1-1-21 of Table 1, and represent compounds numbered in turn 5-1-5-21.
Table 6: in the general formula I, when R2＝Br，R3＝Ph(CH2)，R4＝H，R5＝R6＝CH3，R7，R8＝-(CH2)5When X is O, the substituent R1In accordance with the substituents shown in Table 1, the substituents correspond in turn to 1-1-1-21 of Table 1, and represent compounds numbered in turn 6-1-6-21.
Table 7: in the general formula I, when R2＝R3＝R4＝H，R5＝CH3，R6＝Ph，R7，R8＝-(CH2)5-, X ═ O, substituent R1In accordance with the substituents shown in Table 1, the substituents correspond in turn to 1-1-1-21 of Table 1, and represent the compounds having the numbers in turn from 7-1 to 7-21.
Table 8: in the general formula I, when R2＝Cl，R3＝R4＝H，R5＝CH3，R6＝Ph，R7，R8＝-(CH2)5-, X ═ O, substituent R1In accordance with the substituents shown in Table 1, the substituents are in turn in pairsThe numbers of the compounds represented by 1-1-1-21 in Table 1 are 8-1-8-21 in this order.
Table 9: in the general formula I, when R2＝Br，R3＝R4＝H，R5＝CH3，R6＝Ph，R7，R8＝-(CH2)5-, X ═ O, substituent R1In accordance with the substituents shown in Table 1, the substituents correspond in turn to 1-1-1-21 of Table 1, and represent the compounds in the number sequence 9-1-9-21.
Table 10: in the general formula I, when R2＝R4＝H，R3＝Ph(CH2)，R5＝CH3，R6＝Ph，R7，R8＝-(CH2)5-, X ═ O, substituent R1In accordance with the substituents shown in Table 1, the substituents correspond in turn to 1-1-1-21 of Table 1, and represent the compounds having the numbers of 10-1-10-21 in turn.
Table 11: in the general formula I, when R2＝Cl，R3＝Ph(CH2)，R4＝H，R5＝CH3，R6＝Ph，R7，R8＝-(CH2)5-, X ═ O, substituent R1In accordance with the substituents shown in Table 1, the substituents correspond in sequence to 1-1-1-21 of Table 1, and represent the compounds numbered in sequence from 11-1-11-21.
Table 12: in the general formula I, when R2＝Br，R3＝Ph(CH2)，R4＝H，R5＝CH3，R6＝Ph，R7，R8＝-(CH2)5-, X ═ O, substituent R1In accordance with the substituents shown in Table 1, the substituents correspond in turn to 1-1-1-21 of Table 1, and represent the compounds having the numbers of 12-1-12-21 in turn.
Table 13: in the general formula I, when R2＝R3＝R4＝H，R5＝R6＝CH3，R7，R8＝-(CH2)4-, X ═ O, substituent R1In accordance with the substituents shown in Table 1, the substituents correspond in turn to 1-1-1-21 of Table 1, and represent the compounds having the numbers of 13-1-13-21 in turn.
Table 14: in the general formula I, when R2＝Cl，R3＝R4＝H，R5＝R6＝CH3，R7，R8＝-(CH2)4-, X ═ O, substituent R1In accordance with the substituents shown in Table 1, the substituents correspond in turn to 1-1-1-21 of Table 1, and represent the compounds numbered in turn 14-1-14-21.
Table 15: in the general formula I, when R2＝Br，R3＝R4＝H，R5＝R6＝CH3，R7，R8＝-(CH2)4-, X ═ O, substituent R1In accordance with the substituents shown in Table 1, the substituents correspond in turn to 1-1-1-21 of Table 1, representing compounds numbered in turn 15-1-15-21.
Table 16: in the general formula I, when R2＝R4＝H，R3＝Ph(CH2)，R5＝R6＝CH3，R7，R8＝-(CH2)4-, X ═ O, substituent R1In accordance with the substituents shown in Table 1, the substituents correspond in turn to 1-1-1-21 of Table 1, and represent the compounds having the numbers of 16-1-16-21 in turn.
Table 17: in the general formula I, when R2＝Cl，R3＝Ph(CH2)，R4＝H，R5＝R6＝CH3，R7，R8＝-(CH2)4-, X ═ O, substituent R1In accordance with the substituents shown in Table 1, the substituents correspond in turn to 1-1-1-21 of Table 1, and represent the compounds in the number sequence 17-1-17-21.
Table 18: in the general formula I, when R2＝Br，R3＝Ph(CH2)，R4＝H，R5＝R6＝CH3，R7，R8＝-(CH2)4When X is O, the substituent R1In accordance with the substituents shown in Table 1, the substituents correspond in turn to 1-1-1-21 of Table 1, and represent the compounds in the number sequence 18-1-18-21.
Table 19: in the general formula I, when R2＝R3＝R4＝H，R5＝CH3，R6＝Ph，R7，R8＝-(CH2)4When X is O, the substituent R1In accordance with the substituents shown in Table 1, the substituents correspond in turn to 1-1-1-21 of Table 1, and represent the compounds having the numbers of 19-1-19-21 in turn.
Table 20: in the general formula I, when R2＝Cl，R3＝R4＝H，R5＝CH3，R6＝Ph，R7，R8＝-(CH2)4-, X ═ O, substituent R1In accordance with the substituents shown in Table 1, the substituents correspond in turn to 1-1-1-21 of Table 1, and represent the compounds having the numbers of 20-1-20-21 in turn.
Table 21: in the general formula I, when R2＝Br，R3＝R4＝H，R5＝CH3，R6＝Ph，R7，R8＝-(CH2)4-, X ═ O, substituent R1In accordance with the substituents shown in Table 1, the substituents correspond in turn to 1-1-1-21 of Table 1, and represent the compounds numbered in turn 21-1-21.
Table 22: in the general formula I, when R2＝R4＝H，R3＝Ph(CH2)，R5＝CH3，R6＝Ph，R7，R8＝-(CH2)4-, X ═ O, substituent R1In accordance with the substituents shown in Table 1, the substituents correspond in turn to 1-1-1-21 of Table 1, and represent the compounds having the numbers in turn of 22-1-22-21.
Table 23: in the general formula I, when R2＝Cl，R3＝Ph(CH2)，R4＝H，R5＝CH3，R6＝Ph，R7，R8＝-(CH2)4-, X ═ O, substituent R1In accordance with the substituents shown in Table 1, the substituents correspond in turn to 1-1-1-21 of Table 1, and represent the compounds in the number sequence 23-1-23-21.
Table 24: in the general formula I, when R2＝Br，R3＝Ph(CH2)，R4＝H，R5＝CH3，R6＝Ph，R7，R8＝-(CH2)4-, X ═ O, substituent R1In accordance with the substituents shown in Table 1, the substituents correspond in turn to 1-1-1-21 of Table 1, and represent the compounds having the numbers of 24-1-24-21 in turn.
Table 25: in the general formula I, when R2＝R3＝R4＝H，R5＝R6＝CH3，R7，R8＝-(CH2)5When X is S, the substituent R1In accordance with the substituents shown in Table 1, the substituents correspond in turn to 1-1-1-21 of Table 1, and represent the compounds having the numbers of 25-1-25-21 in turn.
Table 26: in the general formula I, when R2＝Cl，R3＝R4＝H，R5＝R6＝CH3，R7，R8＝-(CH2)5When X is S, the substituent R1In accordance with the substituents shown in Table 1, the substituents correspond in turn to 1-1-1-21 of Table 1, and represent the compounds having the numbers of 26-1-26-21 in turn.
Table 27: in the general formula I, when R2＝Br，R3＝R4＝H，R5＝R6＝CH3，R7，R8＝-(CH2)5When X is S, the substituent R1In accordance with the substituents shown in Table 1, the substituents correspond in turn to 1-1-1-21 of Table 1, and represent the compounds having the numbers of 27-1-27-21 in turn.
Table 28: in the general formula I, when R2＝R4＝H，R3＝Ph(CH2)，R5＝R6＝CH3，R7，R8＝-(CH2)5When X is S, the substituent R1In accordance with the substituents shown in Table 1, the substituents correspond in turn to 1-1-1-21 of Table 1, and represent the compounds having the numbers in turn from 28-1-28-21.
Table 29: in the general formula I, when R2＝Cl，R3＝Ph(CH2)，R4＝H，R5＝R6＝CH3，R7，R8＝-(CH2)5When X is S, the substituent R1In accordance with the substituents shown in Table 1, the substituents correspond in turn to 1-1-1-21 of Table 1, and represent the compounds numbered in turn 29-1-29-21.
Table 30: in the general formula I, when R2＝Br，R3＝Ph(CH2)，R4＝H，R5＝R6＝CH3，R7，R8＝-(CH2)5When X is S, the substituent R1In accordance with the substituents shown in Table 1, the substituents correspond in turn to 1-1-1-21 of Table 1, and represent the compounds having the numbers of 30-1-30-21 in turn.
Table 31: in the general formula I, when R2＝R3＝R4＝H，R5＝CH3，R6＝Ph，R7，R8＝-(CH2)5When X is S, the substituent R1In accordance with the substituents shown in Table 1, the substituents correspond in turn to 1-1-1-21 of Table 1, and represent the compound numbers in turn 31-1-31-21.
Table 32: in the general formula I, when R2＝Cl，R3＝R4＝H，R5＝CH3，R6＝Ph，R7，R8＝-(CH2)5When X is S, the substituent R1In accordance with the substituents shown in Table 1, the substituents correspond in turn to 1-1-1-21 of Table 1, and represent the compounds having the numbers in turn from 32-1 to 32-21.
Table 33: in the general formula I, when R2＝Br，R3＝R4＝H，R5＝CH3，R6＝Ph，R7，R8＝-(CH2)5When X is S, the substituent R1In accordance with the substituents shown in Table 1, the substituents correspond in turn to 1-1-1-21 of Table 1, and represent the compound numbers 33-1-33-21 in turn.
Table 34: in the general formula I, when R2＝R4＝H，R3＝Ph(CH2)，R5＝CH3，R6＝Ph，R7，R8＝-(CH2)5When X is S, the substituent R1In accordance with the substituents shown in Table 1, the substituents correspond to 1-1-1-21 of Table 1 in the order named, and represent compoundsThe numbers are 34-1-34-21 in sequence.
Table 35: in the general formula I, when R2＝Cl，R3＝Ph(CH2)，R4＝H，R5＝CH3，R6＝Ph，R7，R8＝-(CH2)5When X is S, the substituent R1In accordance with the substituents shown in Table 1, the substituents correspond in sequence to 1-1-1-21 of Table 1, and represent the numbers of the compounds in sequence from 35-1 to 35-21.
Table 36: in the general formula I, when R2＝Br，R3＝Ph(CH2)，R4＝H，R5＝CH3，R6＝Ph，R7，R8＝-(CH2)5When X is S, the substituent R1In accordance with the substituents shown in Table 1, the substituents correspond in turn to 1-1-1-21 of Table 1, and represent the compound numbers in turn 36-1-36-21.
Table 37: in the general formula I, when R2＝R3＝R4＝H，R5＝R6＝CH3，R7，R8＝-(CH2)4When X is S, the substituent R1In accordance with the substituents shown in Table 1, the substituents correspond in turn to 1-1-1-21 of Table 1, and represent the compound numbers in turn 37-1-37-21.
Table 38: in the general formula I, when R2＝Cl，R3＝R4＝H，R5＝R6＝CH3，R7，R8＝-(CH2)4When X is S, the substituent R1In accordance with the substituents shown in Table 1, the substituents correspond in turn to 1-1-1-21 of Table 1, and represent the compounds numbered in turn 38-1-38-21.
Table 39: in the general formula I, when R2＝Br，R3＝R4＝H，R5＝R6＝CH3，R7，R8＝-(CH2)4When X is S, the substituent R1In accordance with the substituents shown in Table 1, the substituents correspond in turn to 1-1-1-21 of Table 1, and represent the compounds having the numbers in turn from 39-1 to 39-21.
Table 40: in the general formula I, when R2＝R4＝H，R3＝Ph(CH2)，R5＝R6＝CH3，R7，R8＝-(CH2)4When X is S, the substituent R1In accordance with the substituents shown in Table 1, the substituents correspond in turn to 1-1-1-21 of Table 1, and represent the compounds having the numbers of 40-1-40-21 in turn.
Table 41: in the general formula I, when R2＝Cl，R3＝Ph(CH2)，R4＝H，R5＝R6＝CH3，R7，R8＝-(CH2)4When X is S, the substituent R1In accordance with the substituents shown in Table 1, the substituents correspond in turn to 1-1-1-21 of Table 1, and represent the compounds numbered in turn 41-1-41-21.
Table 42: in the general formula I, when R2＝Br，R3＝Ph(CH2)，R4＝H，R5＝R6＝CH3，R7，R8＝-(CH2)4When X is S, the substituent R1In accordance with the substituents shown in Table 1, the substituents correspond in turn to 1-1-1-21 of Table 1, and represent the compounds having the numbers of 42-1-42-21 in turn.
Table 43: in the general formula I, when R2＝R3＝R4＝H，R5＝CH3，R6＝Ph，R7，R8＝-(CH2)4When X is S, the substituent R1In accordance with the substituents shown in Table 1, the substituents correspond in turn to 1-1-1-21 of Table 1, and represent the compounds having the numbers of 43-1-43-21 in turn.
Table 44: in the general formula I, when R2＝Cl，R3＝R4＝H，R5＝CH3，R6＝Ph，R7，R8＝-(CH2)4When X is S, the substituent R1In accordance with the substituents shown in Table 1, the substituents correspond in turn to 1-1-1-21 of Table 1, and represent the compounds having the numbers in turn from 44-1 to 44-21.
Table 45: in the general formula I, when R2＝Br，R3＝R4＝H，R5＝CH3，R6＝Ph，R7，R8＝-(CH2)4When X is S, the substituent R1In accordance with the substituents shown in Table 1, the substituents correspond in turn to 1-1-1-21 of Table 1, and represent the compounds having the numbers of 45-1-45-21 in turn.
Table 46: in the general formula I, when R2＝R4＝H，R3＝Ph(CH2)，R5＝CH3，R6＝Ph，R7，R8＝-(CH2)4When X is S, the substituent R1In accordance with the substituents shown in Table 1, the substituents correspond in turn to 1-1-1-21 of Table 1, and represent the compound numbers in turn 46-1-46-21.
Table 47: in the general formula I, when R2＝Cl，R3＝Ph(CH2)，R4＝H，R5＝CH3，R6＝Ph，R7，R8＝-(CH2)4When X is S, the substituent R1In accordance with the substituents shown in Table 1, the substituents correspond in turn to 1-1-1-21 of Table 1, and represent the compounds having the numbers in turn 47-1-47-21.
Table 48: in the general formula I, when R2＝Br，R3＝Ph(CH2)，R4＝H，R5＝CH3，R6＝Ph，R7，R8＝-(CH2)4When X is S, the substituent R1In accordance with the substituents shown in Table 1, the substituents correspond in turn to 1-1-1-21 of Table 1, and represent the compounds having the numbers of 48-1-48-21 in turn.
Table 49: in the general formula I, when R2＝R3＝R4＝H，R5＝R6＝R7＝R8＝CH3When X is O, the substituent R1In accordance with the substituents shown in Table 1, the substituents correspond in turn to 1-1-1-21 of Table 1, and represent the compounds numbered in turn 49-1-49-21.
Table 50: in the general formula I, when R2＝Cl，R3＝R4＝H，R5＝R6＝R7＝R8＝CH3When X is O, the substituent R1And substitution shown in Table 1The radicals are consistent, the substituents correspond to 1-1-1-21 in sequence in the table 1, and the number of the representative compound is 50-1-50-21 in sequence.
Table 51: in the general formula I, when R2＝Br，R3＝R4＝H，R5＝R6＝R7＝R8＝CH3When X is O, the substituent R1In accordance with the substituents shown in Table 1, the substituents correspond in turn to 1-1-1-21 of Table 1, and represent the compound numbers in turn 51-1-51-21.
Table 52: in the general formula I, when R2＝R4＝H，R3＝Ph(CH2)，R5＝R6＝R7＝R8＝CH3When X is O, the substituent R1In accordance with the substituents shown in Table 1, the substituents correspond in turn to 1-1-1-21 of Table 1, and represent the compound numbers 52-1-52-21 in turn.
Table 53: in the general formula I, when R2＝Cl，R3＝Ph(CH2)，R4＝H，R5＝R6＝R7＝R8＝CH3When X is O, the substituent R1In accordance with the substituents shown in Table 1, the substituents correspond in turn to 1-1-1-21 of Table 1, and represent the compounds numbered in turn from 53-1-53-21.
Table 54: in the general formula I, when R2＝Br，R3＝Ph(CH2)，R4＝H，R5＝R6＝R7＝R8＝CH3When X is O, the substituent R1In accordance with the substituents shown in Table 1, the substituents correspond in turn to 1-1-1-21 of Table 1, and represent the compound numbers in turn 54-1-54-21.
Table 55: in the general formula I, when R2＝R3＝R4＝H，R5＝R7＝R8＝CH3，R6When Ph and X is O, the substituent R1In accordance with the substituents shown in Table 1, the substituents correspond in turn to 1-1-1-21 of Table 1, and represent the compounds numbered in turn from 55-1-55-21.
Table 56: in the general formula I, when R2＝Cl，R3＝R4＝H，R5＝R7＝R8＝CH3，R6When Ph and X is O, the substituent R1In accordance with the substituents shown in Table 1, the substituents correspond in turn to 1-1-1-21 of Table 1, and represent the compounds having the numbers of 56-1-56-21 in turn.
Table 57: in the general formula I, when R2＝Br，R3＝R4＝H，R5＝R7＝R8＝CH3，R6When Ph and X is O, the substituent R1In accordance with the substituents shown in Table 1, the substituents correspond in turn to 1-1-1-21 of Table 1, and represent the compounds having the numbers of 57-1-57-21 in turn.
Table 58: in the general formula I, when R2＝R4＝H，R3＝Ph(CH2)，R5＝R7＝R8＝CH3，R6When Ph and X is O, the substituent R1In accordance with the substituents shown in Table 1, the substituents correspond in turn to 1-1-1-21 of Table 1, and represent the compound numbers in turn 58-1-58-21.
Table 59: in the general formula I, when R2＝Cl，R3＝Ph(CH2)，R4＝H，R5＝R7＝R8＝CH3，R6When Ph and X is O, the substituent R1In accordance with the substituents shown in Table 1, the substituents correspond in turn to 1-1-1-21 of Table 1, and represent the compound numbers of 59-1-59-21 in turn.
Table 60: in the general formula I, when R2＝Br，R3＝Ph(CH2)，R4＝H，R5＝R7＝R8＝CH3，R6When Ph and X is O, the substituent R1In accordance with the substituents shown in Table 1, the substituents correspond in turn to 1-1-1-21 of Table 1, and represent the compounds having the numbers of 60-1-60-21 in turn.
Table 61: in the general formula I, when R2＝R3＝R4＝H，R5＝R6＝R7＝R8＝CH3When X is S, the substituent R1In accordance with the substituents shown in Table 1, the substituents correspond in turn to 1-1-1-21 of Table 1, and represent the compound numbers in turn 61-1-61-21.
Table 62: in the general formula I, when R2＝Cl，R3＝R4＝H，R5＝R6＝R7＝R8＝CH3When X is S, the substituent R1In accordance with the substituents shown in Table 1, the substituents correspond in turn to 1-1-1-21 of Table 1, and represent the compounds having the numbers in turn from 62-1 to 62-21.
Table 63: in the general formula I, when R2＝Br，R3＝R4＝H，R5＝R6＝R7＝R8＝CH3When X is S, the substituent R1In accordance with the substituents shown in Table 1, the substituents correspond in turn to 1-1-1-21 of Table 1, and represent the compounds numbered in turn 63-1-63-21.
Table 64: in the general formula I, when R2＝R4＝H，R3＝Ph(CH2)，R5＝R6＝R7＝R8＝CH3When X is S, the substituent R1In accordance with the substituents shown in Table 1, the substituents correspond in turn to 1-1-1-21 of Table 1, and represent the compound numbers of 64-1-64-21 in turn.
Table 65: in the general formula I, when R2＝Cl，R3＝Ph(CH2)，R4＝H，R5＝R6＝R7＝R8＝CH3When X is S, the substituent R1In accordance with the substituents shown in Table 1, the substituents correspond in turn to 1-1-1-21 of Table 1, and represent the compounds having the numbers in turn from 65-1 to 65-21.
Table 66: in the general formula I, when R2＝Br，R3＝Ph(CH2)，R4＝H，R5＝R6＝R7＝R8＝CH3When X is S, the substituent R1In accordance with the substituents shown in Table 1, the substituents correspond in turn to 1-1-1-21 of Table 1, and represent the compound numbers in turn 66-1-66-21.
Table 67: in the general formula I, when R2＝R3＝R4＝H，R5＝R7＝R8＝CH3，R6When Ph and X is S, the substituent R1In accordance with the substituents shown in Table 1, the substituents correspond in sequence to1-1-1-21 in Table 1 represents the compound numbers 67-1-67-21 in this order.
Table 68: in the general formula I, when R2＝Cl，R3＝R4＝H，R5＝R7＝R8＝CH3，R6When Ph and X is S, the substituent R1In accordance with the substituents shown in Table 1, the substituents correspond in turn to 1-1-1-21 of Table 1, and represent the compounds having the numbers of 68-1-68-21 in turn.
Table 69: in the general formula I, when R2＝Br，R3＝R4＝H，R5＝R7＝R8＝CH3，R6When Ph and X is S, the substituent R1In accordance with the substituents shown in Table 1, the substituents correspond in turn to 1-1-1-21 of Table 1, and represent the compound numbers 69-1-69-21 in turn.
Table 70: in the general formula I, when R2＝R4＝H，R3＝Ph(CH2)，R5＝R7＝R8＝CH3，R6When Ph and X is S, the substituent R1In accordance with the substituents shown in Table 1, the substituents correspond in turn to 1-1-1-21 of Table 1, and represent the compounds in the number sequence 70-1-70-21.
Table 71: in the general formula I, when R2＝Cl，R3＝Ph(CH2)，R4＝H，R5＝R7＝R8＝CH3，R6When Ph and X is S, the substituent R1In accordance with the substituents shown in Table 1, the substituents correspond in turn to 1-1-1-21 of Table 1, and represent the compound numbers in turn 71-1-71-21.
Table 72: in the general formula I, when R2＝Br，R3＝Ph(CH2)，R4＝H，R5＝R7＝R8＝CH3，R6When Ph and X is S, the substituent R1In accordance with the substituents shown in Table 1, the substituents correspond in turn to 1-1-1-21 of Table 1, and represent the compounds having the numbers of 72-1-72-21 in turn.
Table 73: in the general formula I, when R2＝Cl，R3＝H，R4＝CN，R5＝R6＝CH3，R7，R8＝-(CH2)5When X is S, the substituent R1In accordance with the substituents shown in Table 1, the substituents correspond in turn to 1-1-1-21 of Table 1, and represent the compound numbers in turn 73-1-73-21.
Table 74: in the general formula I, when R2＝Cl，R3＝H，R4＝CN，R5＝CH3，R6＝Ph，R7，R8＝-(CH2)5When X is S, the substituent R1In accordance with the substituents shown in Table 1, the substituents correspond in turn to 1-1-1-21 of Table 1, and represent the compound numbers 74-1-74-21 in turn.
Table 75: in the general formula I, when R2＝Cl，R3＝H，R4＝CN，R5＝R6＝R7＝R8＝CH3When X is S, the substituent R1In accordance with the substituents shown in Table 1, the substituents correspond in sequence to 1-1-1-21 of Table 1, and represent the compounds in the sequence of compound numbers 75-1-75-21.
Table 76: in the general formula I, when R2＝Cl，R3＝H，R4＝CN，R5＝R7＝R8＝CH3，R6When Ph and X is S, the substituent R1In accordance with the substituents shown in Table 1, the substituents correspond in turn to 1-1-1-21 of Table 1, and represent the compounds having the numbers of 76-1-76-21 in turn.
Table 77: in the general formula I, when R2＝Cl，R3＝H，R4＝CN，R5＝R6＝CH3，R7，R8＝-(CH2)5-, X ═ O, substituent R1In accordance with the substituents shown in Table 1, the substituents correspond in turn to 1-1-1-21 of Table 1, and represent the compound numbers in turn 77-1-77-21.
Table 78: in the general formula I, when R2＝Cl，R3＝H，R4＝CN，R5＝CH3，R6＝Ph，R7，R8＝-(CH2)5-, X ═ O, substituent R1In accordance with the substituents shown in Table 1, the substituents correspond in turn to those of Table 11-1-1-21, and the number of the representative compound is 78-1-78-21 in sequence.
Table 79: in the general formula I, when R2＝Cl，R3＝H，R4＝CN，R5＝R6＝R7＝R8＝CH3When X is O, the substituent R1In accordance with the substituents shown in Table 1, the substituents correspond in turn to 1-1-1-21 of Table 1, and represent the compounds whose numbers are in turn 79-1-79-21.
Table 80: in the general formula I, when R2＝Cl，R3＝H，R4＝CN，R5＝R7＝R8＝CH3，R6When Ph and X is O, the substituent R1In accordance with the substituents shown in Table 1, the substituents correspond in turn to 1-1-1-21 of Table 1, and represent the compounds in the numbers of 80-1-80-21 in turn.
The compounds of the invention are prepared according to the following process, the reaction scheme being as follows, wherein the groups are as defined above unless otherwise stated:
according to the different definitions of X, the compounds of general formula I are prepared as follows:
(1) when X ═ O (with R)4＝H，R5＝CH3For example),
Figure BDA0001638987870000141
(2) when X ═ O (with R)4＝CN，R5＝CH3For example),
Figure BDA0001638987870000142
(3) when X ═ S (with R)4＝H，R5＝CH3For example),
Figure BDA0001638987870000143
(4) when X is NR10When (with R)4＝R10＝H，R5＝CH3For example) of the above-described,
Figure BDA0001638987870000144
intermediates II-1, II-2, VI-1 and III-1 respectively; and intermediates V-1 and III-2, can react in a suitable solvent under alkaline conditions to obtain compounds of general formulas I-1, I-2, I-4 and I-3 respectively;
suitable bases may be selected from, for example, potassium hydroxide, sodium carbonate, potassium carbonate, sodium bicarbonate, triethylamine, pyridine, sodium methoxide, sodium ethoxide, sodium hydride, potassium tert-butoxide, sodium tert-butoxide, etc.
The reaction is carried out in a suitable solvent, which may be selected from, for example, tetrahydrofuran, 1, 4-dioxane, acetonitrile, toluene, xylene, benzene, N-dimethylformamide, N-methylpyrrolidone, dimethylsulfoxide, acetone, or butanone.
The reaction temperature may be between room temperature and the boiling temperature of the solvent, and is usually 20 to 100 ℃.
The reaction time is 30 minutes to 20 hours, usually 1 to 10 hours.
When R is1In the case of hydrogen or alkyl, the intermediate III moiety is prepared commercially or by reference to known procedures for the preparation of WO 2016112298.
When R is1Is benzyl, substituted by 1-5R9Benzyl further substituted, heteroarylmethyl, or substituted by 1-5R9For further substituted heteroarylmethyl, intermediate III refers to known procedures for the preparation of WO 2017069226.
Intermediate IV is prepared with reference to CN 104370891A; Chen.J.chem.2017, 35, 1133-1140; synthesis.2017,49,4663-4669.
Intermediate II-1 was prepared from intermediate IV-1 by methods described in adv. Synth. Catal.2013,355, 947-956.
Intermediate II-2 was prepared from intermediate IV-1 by methods described in Bioorganic & Medicinal Chemistry,2004,12, 979-.
Intermediate V-1 was prepared from intermediate II-1 by the method described in CN 103772356.
Intermediate VI-1 was prepared from intermediate V-1 by the method described in Journal of Organic Chemistry,1983,48, 3412-22.
The compound of the general formula I shows excellent activity on various pathogenic bacteria in agriculture or other fields. Therefore, the technical scheme of the invention also comprises the application of the compound shown in the general formula I in the preparation of bactericides in agriculture, horticulture or other fields.
The examples of diseases mentioned below are intended only to illustrate the invention, but in no way limit it.
The compounds of the general formula I can be used for controlling the following diseases: oomycete diseases such as downy mildew (cucumber downy mildew, rape downy mildew, soybean downy mildew, beet downy mildew, sugarcane downy mildew, tobacco downy mildew, pea downy mildew, loofah downy mildew, wax gourd downy mildew, melon downy mildew, Chinese cabbage downy mildew, spinach downy mildew, radish downy mildew, grape downy mildew, onion downy mildew), white rust (rape white rust, Chinese cabbage white rust), damping-off (rape damping-off, tobacco damping-off, tomato damping-off, pepper damping-off, eggplant damping-off, cucumber damping-off, cotton seedling damping-off), cotton rot (hot pepper rot, loofah sponge rot, wax gourd blight), epidemic diseases (broad bean blight, cucumber blight, pumpkin blight, melon blight, hot pepper, leek blight, garlic blight, cotton blight, tomato blight, etc.; fungi imperfecti diseases such as wilt (sweet potato wilt, cotton wilt, sesame wilt, castor wilt, tomato wilt, bean wilt, cucumber wilt, pumpkin wilt, winter melon wilt, watermelon wilt, sweet melon wilt, hot pepper wilt, broad bean wilt, rape wilt, soybean wilt), root rot (hot pepper root rot, eggplant root rot, bean rot, cucumber root rot, bitter gourd root rot, cotton black root rot, broad bean root rot), damping off (seedling blight of cotton, sesame seedling blight, hot pepper seedling blight, cucumber damping off, cabbage stalk rot), anthracnose (sorghum anthracnose, cotton anthracnose, kenaf anthracnose, jute anthracnose, flax anthracnose, tobacco anthracnose, mulberry leaf, hot pepper, bean disease, cucumber anthracnose, red sesame anthracnose, jute anthracnose, flax anthracnose, tobacco anthracnose, eggplant disease, hot pepper anthracnose, vegetable bean disease, and cucumber blight, Balsam pear anthracnose, pumpkin anthracnose, wax gourd anthracnose, watermelon anthracnose, melon anthracnose, litchi anthracnose), verticillium wilt (cotton verticillium wilt, sunflower verticillium wilt, tomato verticillium wilt, hot pepper verticillium wilt, eggplant verticillium wilt), scab (pumpkin scab, wax gourd scab, melon scab), gray mold (boll gray mold, red ramie gray mold, tomato gray mold, hot pepper gray mold, bean gray mold, celery gray mold, spinach gray mold, kiwi gray mold), brown spot (cotton brown spot, jute brown spot, beet brown spot, peanut brown spot, pepper brown spot, wax gourd brown spot, soybean brown spot, sunflower brown spot, pea brown spot, broad bean brown spot), black spot (flax brown spot, rape black spot, sesame black spot, sunflower black spot, castor black spot, tomato black spot, tomato black spot, tomato black spot, tomato black spot, tomato black spot, tomato, Pepper black spot, eggplant black spot, bean black spot, cucumber black spot, celery black spot, carrot black rot, carrot black spot, apple black spot, peanut black spot), spot blight (tomato spot blight, pepper spot blight, celery spot blight), early blight (tomato early blight, pepper early blight, eggplant early blight, potato early blight, celery early blight), ring spot (soybean ring spot, sesame ring spot, bean ring spot), leaf blight (sesame leaf blight, sunflower leaf blight, watermelon leaf blight, melon leaf blight), stem base rot (tomato stem base rot, bean stem base rot), and others (corn round spot, kenaf waist fold, rice blast, black sheath blight, sugarcane eye spot, cotton boll aspergillosis, peanut crown rot, soybean stem blight, soybean black spot, melon big spot, peanut net spot, tea leaf spot, red leaf spot, black leaf spot, peanut net spot, tea leaf spot, tomato black spot, potato leaf spot, potato black spot, tomato leaf spot, etc, Pepper white spot disease, white gourd leaf spot disease, celery black rot disease, spinach heart rot disease, kenaf leaf mold disease, kenaf spot disease, jute stem spot disease, soybean purple spot disease, sesame leaf spot disease, castor gray spot disease, tea brown leaf spot disease, eggplant brown orbicular spot disease, kidney bean red spot disease, bitter gourd leukoderma, watermelon spot disease, jute bottom rot disease, sunflower root stem rot disease, kidney bean carbon rot disease, soybean target spot disease, eggplant rod spore leaf spot disease, cucumber target spot disease, tomato leaf mold, eggplant leaf mold, broad bean red spot disease and the like); basidiomycete diseases such as rust (wheat stripe rust, wheat stalk rust, wheat leaf rust, peanut rust, sunflower rust, sugarcane rust, leek rust, onion rust, chestnut rust, soybean rust), smut (maize head smut, maize smut, sorghum head smut, sorghum loose smut, sorghum stalk smut, chestnut kernel smut, sugarcane head smut, kidney bean rust) and others (such as wheat sharp eyespot, rice sheath blight, etc.); ascomycetous diseases, such as powdery mildew (wheat powdery mildew, rape powdery mildew, sesame powdery mildew, sunflower powdery mildew, beet powdery mildew, eggplant powdery mildew, pea powdery mildew, towel gourd powdery mildew, pumpkin powdery mildew, wax gourd powdery mildew, melon powdery mildew, grape powdery mildew, broad bean powdery mildew), sclerotinia rot (flax sclerotinia rot, rape sclerotinia rot, soybean sclerotinia rot, peanut sclerotinia rot, tobacco sclerotinia rot, pepper sclerotinia rot, eggplant sclerotinia rot, kidney bean sclerotinia rot, pea sclerotinia rot, cucumber sclerotinia rot, bitter gourd sclerotinia rot, wax gourd sclerotinia rot, watermelon sclerotinia rot, celery sclerotinia rot), scab (apple scab, pear scab) and the like.
Owing to their positive properties, the abovementioned compounds can be used advantageously for protecting crops, livestock and breeding animals of agricultural and horticultural importance, as well as the environment which is frequently encountered by humans, against harmful bacteria.
Detailed Description
The following specific examples are intended to further illustrate the invention, but the invention is in no way limited to these examples (all materials are commercially available unless otherwise indicated).
Synthetic examples
Example 1: preparation of intermediate 3- (1-hydroxyethyl) -4-phenyl-1-oxaspiro [4.5] dec-3-en-2-one
The intermediate 3-acetyl-4-phenyl-1-oxaspiro [4.5]]Dec-3-en-2-one (2.70g, 0.01mol) was dissolved in 30mL ethanol and NaBH was added thereto4(0.57g, 0.015mol), stirring and reacting for 1h at room temperature, after TLC monitoring reaction, decompressing and distilling to remove the solvent, then adding ethyl acetate and water for extraction, washing an organic phase with saturated common salt, drying with anhydrous magnesium sulfate, filtering, decompressing and desolventizing to obtain 2.50g of white solid with a melting point of 114-.1H NMR(600MHz,CDCl3)δ:0.95-1.95+1.64-1.79(m,10H,cyclohexyl-10H),1.40(d,J＝6.6Hz,3H,CH3),3.07(d,J＝9.6Hz,1H,OH),4.37(q,1H,CH),7.13-7.15(m,2H,Ph-3,5-2H),7.44-7.45(m,3H,Ph-2,4,6-3H)；13C NMR(CDCl3,150MHz)δ:21.91,23.12,24.23,33.21(J＝68.7Hz),63.14,88.53,127.35,128.70,129.09,129.90,131.28,166.03,172.11.HRMS m/z:272.1411[M+H]+(calcd[M+H]+272.1412).
Example 2: preparation of intermediate 3- (1-chloroethyl) -4-phenyl-1-oxaspiro [4.5] dec-3-en-2-one
The intermediate 3- (1-hydroxyethyl) -4-phenyl-1-oxaspiro [4.5]]Dissolving dec-3-en-2-one (2.72g, 0.01mol) in 20mL dichloromethane, dropwise adding thionyl chloride (1mL) under ice bath, stirring at room temperature for reaction for 2h, after TLC monitoring reaction, evaporating under reduced pressure to remove solvent and redundant thionyl chloride, adding water and ethyl acetate for extraction, washing an organic phase with saturated common salt water, drying with anhydrous magnesium sulfate, filtering, and removing solvent under reduced pressure to obtain 2.61g white solid with melting point 126 and 127 ℃, yield 90%250。1H NMR(600MHz,CDCl3)δ:1.05-1.11+1.55-1.82(m,10H,cyclohexyl-10H),1.71(d,J＝7.2Hz,3H,CH3),4.63(q,H,CH),7.19-7.21(m,2H,Ph-3,5-2H),7.47-7.48(m,3H,Ph-2,4,6-3H)；13C NMR(CDCl3,150MHz)δ:21.77,22.42,24.23,33.12(J＝21.6Hz),48.42,87.48,127.31,128.51,128.76,129.33,131.10,168.14,169.70.HRMS m/z:290.1071[M+H]+(calcd[M+H]+290.1074).
Example 3: preparation of the compound 2-tert-butyl-4-chloro-5- (1- (2-oxo-4-phenyl-1-oxaspiro [4.5] dec-3-en-3-yl) ethoxy) pyridazin-3 (2H) -one (Compound 8-9)
Reacting 3- (1-hydroxyethyl) -4-phenyl-1-oxaspiro [4.5]]Dec-3-en-2-one (2.72g, 0.01mol), potassium carbonate (1.66g, 0.012 mol), 2-tert-butyl-4, 5-dichloropyridazin-3 (2H) -one (commercially available, 2.42g, 0.011mol), dissolved in 20mLN, N-dimethylformamide, the reaction mixture was reacted at 80 ℃ for 1H, TLC monitored the completion of the reaction, ethyl acetate and water were added to extract, the organic phase was washed with saturated brine, dried over anhydrous magnesium sulfate, filtered, desolventized under reduced pressure, and the residue was column-layeredSeparating (eluent is ethyl acetate and petroleum ether (boiling range 60-90 deg.C), volume ratio is 1: 4) to obtain compound 8-9, 2.87g, colorless oily substance, yield is 63%254。1H NMR(300MHz,CDCl3)δ:0.80-1.90(m,10H,cyclohexyl-10H),1.58(d,J＝6.6Hz,3H,CH3),1.64(s,9H,t-Bu),5.35(q,1H,CH),6.98-7.01(m,2H,Ph-3,5-2H),7.35-7.42(m,3H,Ph-2,4,6-3H),7.60(s,1H,Pyridazin-H).13C NMR(CDCl3,75MHz)δ:19.96,21.54,23.85,27.55,32.70,32.92,35.75,70.57,88.33,125.47,126.72,128.20,128.33,128.36,129.04,152.19,158.55,170.26,170.63.HRMS m/z:456.1819[M+H]+(calcd[M+H]+456.1816).
Example 4: preparation of the compound 2-tert-butyl-4-chloro-5- (1- (2-oxo-4-phenyl-1-oxaspiro [4.5] dec-3-en-3-yl) ethylthio) pyridazin-3 (2H) -one (Compound 32-9)
Reacting 3- (1-chloroethyl) -4-phenyl-1-oxaspiro [4.5]Deca-3-en-2-one (2.90g, 0.01mol), 2-tert-butyl-4-chloro-5-mercaptopyridazin-3 (2H) -one (commercially available, 2.18g, 0.01mol), potassium carbonate (2.07g, 0.015mol) were dissolved in 20mLN, N-dimethylformamide, the reaction mixture was reacted at 80 ℃ for 2H, TLC monitored for completion of the reaction, ethyl acetate and water were added for extraction, the organic phase was washed with saturated brine, dried over anhydrous magnesium sulfate, filtered, desolventized under reduced pressure, and column chromatography of the residue (eluent ethyl acetate and petroleum ether (boiling range 60-90 ℃) at volume ratio of 1: 6) gave 32-9, 2.55g, white solid, melting point 93-95 ℃ and yield 54%.1H NMR(300MHz,CDCl3)δ:0.80-1.85(m,10H,cyclohexyl-10H),1.60(d,J＝3.6Hz,3H,CH3),1.65(s,9H,t-Bu-9H),4.30(q,1H,CH),7.33-7.37(m,2H,Ph-3,5-2H),7.44-7.48(m,3H,Ph-2,4,6-3H),7.50(s,1H,Pyridazinone-H).13C NMR(CDCl3,75MHz)δ:19.51,21.55,23.90,27.43,32.71,33.28,35.61,65.98,87.66,127.01,127.75,128.36,128.48,129.17,130.68,132.04,138.72,168.38,169.97.HRMS m/z:472.1588[M+H]+(calcd[M+H]+472.1587).
Meanwhile, other compounds represented by the general formula I of the present invention can be obtained by substituting the corresponding raw materials according to the contents described in the above synthetic examples.
Examples of measurement of biological Activity
The compound of the invention has good activity to various germs in the agricultural field.
Example 5: measurement of fungicidal Activity
The compound sample of the invention is used for carrying out in vitro bacteriostatic activity or in vivo protection effect tests on various fungal diseases of plants. The results of the bactericidal activity measurement are shown in the following examples.
(1) In vitro bactericidal activity assay
The measurement method is as follows: a high-throughput screening method is adopted, namely a compound sample to be detected is dissolved by using a proper solvent (the type of the solvent is acetone, methanol, DMF and the like, and is selected according to the dissolving capacity of the solvent on the sample) to prepare a liquid to be detected with the required concentration. Under an ultraclean working environment, adding a solution to be detected into micropores of a 96-hole culture plate, adding a pathogen propagule suspension into the micropore, and placing the treated culture plate in a constant-temperature incubator for culture. And (4) surveying after 24 hours, wherein the germination or growth condition of the pathogen propagules is visually observed during surveying, and the bacteriostatic activity of the compound is evaluated according to the germination or growth condition of the control treatment.
The in vitro bacteriostatic activity (expressed as inhibition) of some compounds was tested as follows:
inhibition rate against rice blast germs:
at a dose of 25ppm, the inhibition rate of compounds 32-9 and the like on rice blast is more than 80%.
(2) In vivo protective Activity assay
The measurement method is as follows: the living potted plant determination method is adopted, i.e. a sample of the compound to be tested is dissolved by a small amount of solvent (the type of the solvent is acetone, methanol, DMF, etc., and is selected according to the dissolving capacity of the solvent to the sample, and the volume ratio of the solvent amount to the liquid spraying amount is equal to or less than 0.05), and diluted by water containing 0.1 percent of Tween 80 to prepare the liquid to be tested with the required concentration. The solution to be tested is sprayed on diseased host plants (the host plants are standard potted seedlings cultured in a greenhouse) on a crop sprayer, and disease inoculation is carried out after 24 hours. According to the characteristics of diseases, inoculating the disease plants needing temperature and moisture control culture, then culturing in an artificial climate chamber, transferring into a greenhouse for culture after the diseases are infected, and directly inoculating and culturing the disease plants without moisture control culture in the greenhouse. The compound disease control effect evaluation is carried out after the control is sufficiently ill (usually, one week).
The results of the in vivo protective activity test of some compounds are as follows:
under the dosage of 400ppm, the content of the active ingredients,
the control effect of the compounds 8-9, 32-9 and the like on cucumber downy mildew is more than 95 percent;
8-9 compounds and the like, and the control effect on wheat powdery mildew is more than 95 percent;
the compound 8-9 and the like have the corn rust prevention effect of more than 95 percent;
32-9 compounds and the like, and the control effect on the melon anthracnose reaches more than 85 percent.
The other compounds of the general formula I according to the invention were tested accordingly in the manner described above for the determination of the biological activity, and also had the corresponding activity.

Claims (4)

1. A pyridazinone-containing butenolide compound is characterized in that: a compound of formula I;
Figure 776512DEST_PATH_IMAGE001
I
R1selected from hydrogen, C1-C4Alkyl or benzyl;
R2selected from halogens;
R3selected from hydrogen;
R4、R5each independently selected from hydrogen, cyano or C1-C4An alkyl group;
R6is selected from phenyl;
R7and R8A saturated five-or six-membered carbocyclic ring with the carbon atom to which it is attached;
x is selected from O or S.
2. The pyridazinonyl butenolide compound according to claim 1, wherein: in the compounds of the general formula I:
R1selected from hydrogen, methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, isobutyl, tert-butyl or benzyl;
R2selected from fluorine, chlorine, bromine or iodine;
R3selected from hydrogen;
R4、R5each independently selected from hydrogen, cyano, methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, isobutyl or tert-butyl;
R6is selected from phenyl;
R7and R8A saturated five-or six-membered carbocyclic ring with the carbon atom to which it is attached;
x is selected from O or S.
3. The pyridazinonyl butenolide compound according to claim 2, wherein: in the compounds of the general formula I:
R1selected from hydrogen, methyl, ethyl, n-propyl, isopropyl, n-butyl or tert-butyl;
R2selected from chlorine or bromine;
R3selected from hydrogen;
R4selected from hydrogen or cyano;
R5selected from hydrogen, methyl, ethyl, n-propyl or isopropyl;
R6is selected from phenyl;
R7and R8A saturated five-or six-membered carbocyclic ring with the carbon atom to which it is attached;
x is selected from O or S.
4. Use of the pyridazinonyl-butenolide-containing compound according to claim 1 as a fungicide drug in the field of agriculture or horticulture.
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