3-phenylisoxazoline-5-carboxamide compound, preparation method therefor, herbicidal composition thereof and use thereof

Abstract

The present invention relates to the field of herbicidal pesticides, and specifically relates to a 3-phenylisoxazolidine-5-carboxamide compound as represented by general formula (I), a stereoisomer thereof, an agriculturally acceptable salt thereof, a preparation method therefor, a herbicidal composition thereof and the use thereof in the field of plant protection. X1, X2, X3, R1, Z and G are as defined herein.

Description

A 3-phenylisoxazoline-5-carboxamide compound, its preparation method, herbicidal composition and application Technical Field

[0001] This invention relates to the field of pesticides and herbicides, specifically to a 3-phenylisooxazoline-5-carboxamide compound, its stereoisomers, its agriculturally acceptable salts, its preparation method, herbicidal compositions, and applications. Background Technology

[0002] Chemical weed control using herbicides is the most economical and effective method for weed control. However, long-term, continuous, and high-dose use of a single herbicide or a herbicide with a single mode of action can easily lead to problems such as herbicide resistance and the evolution of resistance in weeds. Developing new types of pesticides is the core means to solve these problems.

[0003] WO2012130798A8, WO2014048827A1, WO2019145245A1, and WO2020182723A1 describe a 3-phenylisoxazolin-5-carboxamide compound and its use as a herbicide.

[0004] Bayer subsequently developed the herbicide icafolin-methyl (compound I-10 listed in patent WO2018228985A1), which is a mixture of two diastereomers:

[0005] .

[0006] WO2019034602A1 discloses CK1 (listed compound I-25) and CK2 (listed compound I-26) in Table 1 of the specification:

[0007] The herbicidal activity of these known compounds in the prior art, especially their herbicidal activity at low application rates and / or their compatibility with crop plants, still need to be improved. Summary of the Invention

[0008] Therefore, the object of the present invention is to provide compounds that have strong herbicidal activity, especially even at low application rates, sufficiently low toxicity to humans and animals, and / or high compatibility with crops, and that also exhibit a broad activity spectrum across a wide range of undesirable plants.

[0009] Surprisingly, 3-phenylisoxazoline-5-carboxamide compounds of formula (I) as defined below, their stereoisomers, and their agrochemically acceptable salts have been found to have excellent herbicidal activity against a broad spectrum of economically important monocot and dicot annual pests.

[0010] Therefore, the present invention provides 3-phenylisooxazoline-5-carboxamide compounds of formula (I), their stereoisomers, or agriculturally acceptable salts thereof:

[0011] in,

[0012] R1 represents -CN or F.

[0013] or

[0014] Represents C1-C5 alkyl, C3-C6 cycloalkyl, C2-C5 alkenyl, C2-C5 alkynyl or C1-C5 alkoxy, each of which is substituted by m1 groups selected from halogen, -CN, -OH and C1-C5 alkoxy;

[0015] G represents -OR3 or -NR4R5;

[0016] R3 represents H.

[0017] or

[0018] Representing C1-C 12 Alkyl, C3-C7 cycloalkyl, C3-C7 cycloalkyl-C1-C8 alkyl, C2-C8 alkenyl, C2-C8 ynyl, C5-C6 cycloalkenyl, -N=(C1-C6 cycloalkyl), -N=C(C1-C5 alkyl)2, phenyl, C1-C4 alkyl-phenyl, aromatic heterocyclic, or C1-C4 alkyl-aromatic heterocyclic, each optionally surrounded by m3 groups selected from halogen, -CN, -OH, C1-C6 alkoxy, C1-C6 alkoxycarbonyl, aromatic heterocyclic, aryl, and -S(O). n Substitution of the group in R2;

[0019] R4 and R5 independently represent H, -OH, and Cl-C, respectively. 12 Alkyl, C1-C3 alkoxy, C1-C6 alkoxy-C1-C3 alkyl, C1-C6 alkoxy carbonyl-C1-C6 alkyl, N(C1-C3 alkyl)2 or -S(O) n R2,

[0020] or

[0021] R4 and R5 together with the nitrogen atom to which they are attached form saturated, partially unsaturated, or fully unsaturated five-, six-, or seven-membered rings, which may contain r carbon atoms and o oxygen atoms in addition to nitrogen atoms and are optionally substituted by m4 groups selected from halogens, C1-C6 alkyl groups, halo-C1-C6 alkyl groups, oxo groups, and -CO2R6 groups.

[0022] R6 represents H.

[0023] or

[0024] Represents C1-C8 alkyl, C3-C6 cycloalkyl, C3-C8 alkenyl or C3-C8 alkynyl, each optionally substituted with m5 groups selected from halogen, -CN and C1-C2 alkoxy groups;

[0025] Z represents any one of Z-1 to Z-7. The meanings of Z-1 to Z-7 are as follows:

[0026] X3 represents H, F, Cl, Br, or I.

[0027] X1 and X2 independently represent H, F, Cl, Br, I, -OH, -CN, -NO2, and -S(O), respectively. n R2 or -CO2R6,

[0028] or

[0029] Represents C1-C3 alkyl, C1-C3 alkoxy, C3-C4 cycloalkyl, C2-C3 alkenyl or C2-C3 alkynyl, each of which is substituted by m6 groups selected from F, Cl, Br and I;

[0030] R2 represents a C1-C4 alkyl or a C3-C4 cycloalkyl, each of which is substituted by m2 groups selected from F and Cl;

[0031] m1 can be 0, 1, 2, or 3;

[0032] m2 can be 0, 1, 2, or 3;

[0033] m3 is 0, 1, 2, 3, 4, 5, 6, 7 or 8;

[0034] m4 can be 0, 1, 2, 3, 4 or 5;

[0035] m5 can be 0, 1, 2, 3, 4 or 5;

[0036] m6 can be 0, 1, 2, or 3;

[0037] n is 0, 1, or 2;

[0038] o can be 0, 1, or 2;

[0039] r can be 3, 4, 5, or 6.

[0040] Preferably,

[0041] in,

[0042] R1 represents a C1-C3 alkyl, C3-C4 cycloalkyl, C2-C3 alkenyl, C2-C3 alkynyl, or C1-C3 alkoxy group, each of which is substituted by m1 groups selected from the following groups: halogen, -CN, -OH, and C1-C2 alkoxy.

[0043] G represents -OR3 or -NR4R5;

[0044] R3 represents H.

[0045] or

[0046] Representing C1-C 10 Alkyl, C3-C6 cycloalkyl, C3-C6 cycloalkyl-C1-C6 alkyl, C2-C6 alkenyl, C5-C6 cycloalkenyl, -N=(C1-C5 cycloalkyl), -N=C(C1-C3 alkyl)2, phenyl, C1-C3 alkyl-phenyl, aromatic heterocyclic, C1-C3 alkyl-aromatic heterocyclic, or C2-C6 ynyl, each substituted by m3 groups selected from the following: F, Cl, Br, I, -CN, -OH, -S(O). n R2, C1-C4 alkoxy, aryl and aromatic heterocyclic groups;

[0047] R4 and R5 independently represent H, -OH, C1-C6 alkyl, C1-C3 alkoxy, C1-C3 alkoxy, -C1-C3 alkyl, or -S(O). n R2, or

[0048] R4 and R5 together with the nitrogen atom to which they are attached form a saturated or partially unsaturated or fully unsaturated five- or six-membered ring, which may contain r carbon atoms and o oxygen atoms in addition to the nitrogen atom and may optionally be substituted by m4 groups selected from halogen, C1-C6 alkyl, halogen-C1-C6 alkyl, oxo, and -CO2R6 groups.

[0049] R2 represents C1-C4 alkyl;

[0050] R6 represents H.

[0051] or

[0052] Represents C1-C6 alkyl, C3-C6 cycloalkyl, C3-C8 alkenyl or C3-C8 alkynyl, each optionally substituted with m5 groups selected from halogen, -CN and C1-C2 alkoxy groups;

[0053] m1 can be 0, 1, 2, or 3;

[0054] m3 is 0, 1, 2, 3, 4, 5, 6, 7 or 8;

[0055] m4 can be 0, 1, 2, 3, or 4;

[0056] m5 can be 0, 1, 2, or 3;

[0057] n is 0, 1, or 2;

[0058] o can be 0, 1, or 2;

[0059] r is 3, 4, or 5.

[0060] More preferably,

[0061] in,

[0062] R1 represents a C1-C3 alkyl, C2-C3 alkenyl, C2-C3 alkynyl, or C1-C3 alkoxy group, each of which is substituted by m1 groups selected from F, Cl, and Br.

[0063] G represents -OR3 or -NR4R5;

[0064] R3 represents H.

[0065] or

[0066] Represents C1-C7 alkyl, C3-C6 cycloalkyl, C3-C6 cycloalkyl-C1-C6 alkyl, C2-C6 alkenyl, C5-C6 cycloalkenyl, C2-C6 alkynyl, C1-C3 alkoxy-C1-C3 alkyl, -N=C(C1-C3 alkyl)2, phenyl, C1-C3 alkyl-phenyl-, aromatic heterocyclic, C1-C3 alkyl-aromatic heterocyclic-, phenyl-C1-C3 alkyl- or aromatic heterocyclic-C1-C3 alkyl-, each substituted by m3 groups selected from the following: F, Cl, Br, I, -CN, -OH, -OCH3 or -S(O). n R2;

[0067] R4 and R5 independently represent H, -OH, C1-C6 alkyl, C1-C3 alkoxy, or -S(O). n R2;

[0068] or

[0069] R4 and R5 together with the nitrogen atoms they are attached to form saturated five-membered or six-membered rings, which contain four or five carbon atoms in addition to nitrogen atoms.

[0070] R2 represents C1-C3 alkyl;

[0071] m1 can be 0, 1, 2, or 3;

[0072] m3 is 0, 1, 2, 3, 4, 5, 6, 7 or 8;

[0073] n is 0, 1, or 2.

[0074] More preferably,

[0075] in,

[0076] R1 represents -CH3, -CH=CH2, -CF=CH2, -CF3, -CF2H, -CH2F, -CH2Cl, -CF2CH3, or -OCH3;

[0077] G represents -OR3 or -NR4R5;

[0078] R3 represents H.

[0079] or

[0080] Represents -CH3, -CH2CH3, -CH2CH2CH3, -CH(CH3)2, -CH2CH2CH2CH3, -CH2CH(CH3)2, -CH(CH3)CH2CH3, -C(CH3)3, -(CH2)4CH3, -(CH2)5CH3, -(CH2)6CH3, -CH2CH =CH2, -CH2CH2CH=CH2, -CH2CH=CHCH3, -CH(CH3)CH=CH2, -CH2C≡CH, (S)-CH(CH3)C≡CH, (R)-CH(CH3)C≡CH, -CH2C≡CCH3, -CH(CH2CH3)C≡CH, -CH2CH2S(O) n CH3、-CH2CH2S(O) n CH2CH3, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, -CH2-cyclopropyl, -CH2-cyclobutyl, -CH2-cyclopentyl, -CH2-cyclohexyl, -CH2CH2CN, -CH2CF3, -CH2CF2H, -CH2CH2F, -CH2CH2Cl, -CH2CH2Br, -CH2CCl3, -CH2CF2CF3, -CH2(CF2)2H, -CH2(CF2)3H, -CH2(CF2)4H, -CH2CH2OCH3, -(CH2)3OCH3, (S)-CH2CH(CH3)OCH3, (S)-CH(CH3)C H2OCH3, (R)-CH2CH(CH3)OCH3, (R)-CH(CH3)CH2OCH3, -CH2CH2OCH2CH3, -N=C(CH3)2, -C6H5, p-CH3-C6H4-, pF-C6H4-, p-Cl-C6H4-, p-Br-C6H4-, -CH2-C6H5, p-CH3-C6H4-CH2-, pF-C6H4-CH2-, p-Cl-C6H4-CH2-, p-Br-C6H4-CH2-, p-CN-C6H4-CH2-, p-CH3O-C6H4-CH2- or 3-pyridyl;

[0081] n is 0, 1, or 2;

[0082] or

[0083] R4 and R5 independently represent H, -CH3, -CH2CH3, -OH, -OCH3, -OCH2CH3, -OCH(CH3)2, or -SO2CH3, or

[0084] R4 and R5, together with the nitrogen atom they are attached to, form a saturated five- or six-membered ring, which contains four or five carbon atoms in addition to the nitrogen atom.

[0085] More preferably,

[0086] in,

[0087] Z represents Z-1, Z-2, or Z-5;

[0088] X3 represents H or F;

[0089] X1 and X2 each independently represent H, F, Cl, Br, or -CN.

[0090] or

[0091] Represents C1-C3 alkyl or C1-C3 alkoxy groups, each of which is substituted by m6 groups selected from F, Cl and Br;

[0092] m6 can be 0, 1, 2, or 3.

[0093] More preferably,

[0094] in,

[0095] Z represents Z-2;

[0096] X3 represents H or F;

[0097] X1 and X2 each independently represent H, F, Cl, Br, -CH3, -CN, -OCH3, -CF3, -CF2H, -OCF3, or -OCF2H.

[0098] In the definitions of compounds of general formula (I) given above, the terms used in the compilation are generally defined as follows:

[0099] Alkyl groups refer to saturated straight-chain or branched hydrocarbon groups having a specified number of carbon atoms in each case, such as C1-C6-alkyl groups, including methyl, ethyl, propyl, 1-methylethyl, butyl, 1-methylpropyl, 2-methylpropyl, 1,1-dimethylethyl, pentyl, 1-methylbutyl, 2-methylbutyl, 3-methylbutyl, 2,2-dimethylpropyl, 1-ethylpropyl, hexyl, 1,1-dimethylpropyl, 1,2-dimethylpropyl, etc. 1-Methylpentyl, 2-methylpentyl, 3-methylpentyl, 4-methylpentyl, 1,1-dimethylbutyl, 1,2-dimethylbutyl, 1,3-dimethylbutyl, 2,2-dimethylbutyl, 2,3-dimethylbutyl, 3,3-dimethylbutyl, 1-ethylbutyl, 2-ethylbutyl, 1,1,2-trimethylpropyl, 1,2,2-trimethylpropyl, 1-ethyl-1-methylpropyl, and 1-ethyl-2-methylpropyl.

[0100] Halogen-substituted alkyl groups refer to the following straight-chain or branched alkyl groups in which some or all of the hydrogen atoms can be replaced by halogen atoms, such as C1-C2-halogenated alkyl groups, such as chloromethyl, bromomethyl, dichloromethyl, trichloromethyl, fluoromethyl, difluoromethyl, trifluoromethyl, chlorofluoromethyl, dichlorofluoromethyl, chlorodifluoromethyl, 1-chloroethyl, 1-bromoethyl, 1-fluoroethyl, 2-fluoroethyl, 2,2-difluoroethyl, 2,2,2-trifluoroethyl, 2-chloro-2-fluoroethyl, 2-chloro-2,2-difluoroethyl, 2,2,2-dichloro-2-fluoroethyl, 2,2,2-trichloroethyl, pentafluoroethyl, and 1,1,1-trifluoropropyl-2-yl.

[0101] Alkenyl refers to an unsaturated straight-chain or branched hydrocarbon group that has a specified number of carbon atoms and a double bond at any position in each case, such as C2-C6-alkenyl groups, including vinyl, 1-propenyl, 2-propenyl, 1-methylvinyl, 1-butenyl, 2-butenyl, 3-butenyl, 1-methyl-1-propenyl, 2-methyl-1-propenyl, 1-methyl-2-propenyl, 2-methyl-2-propenyl, 1-pentenyl, 2-pentenyl, 3-pentenyl, 4-pentenyl, 1-methyl-1-butenyl, 2-methyl-1-butenyl, 3-methyl-1-butenyl, 1-methyl-2-butenyl, 2-methyl- 2-Butenyl, 3-methyl-2-butenyl, 1-methyl-3-butenyl, 2-methyl-3-butenyl, 3-methyl-3-butenyl, 1,1-dimethyl-2-propenyl, 1,2-dimethyl-1-propenyl, 1,2-dimethyl-2-propenyl, 1-ethyl-1-propenyl, 1-ethyl-2-propenyl, 1-hexenyl, 2-hexenyl, 3-hexenyl, 4-hexenyl, 5-hexenyl, 1-methyl-1-pentenyl, 2-methyl-1-pentenyl, 3-methyl-1-pentenyl, 4-methyl-1-pentenyl, 1-methyl-2-pentenyl, 2-methyl-2-pentenyl, 3-methyl- 2-Pentenyl, 4-Methyl-2-pentenyl, 1-Methyl-3-pentenyl, 2-Methyl-3-pentenyl, 3-Methyl-3-pentenyl, 4-Methyl-3-pentenyl, 1-Methyl-4-pentenyl, 2-Methyl-4-pentenyl, 3-Methyl-4-pentenyl, 4-Methyl-4-pentenyl, 1,1-Dimethyl-2-butenyl, 1,1-Dimethyl-3-butenyl, 1,2-Dimethyl-1-butenyl, 1,2-Dimethyl-2-butenyl, 1,2-Dimethyl-3-butenyl, 1,3-Dimethyl-1-butenyl, 1,3-Dimethyl-2-butenyl, 1,3-Dimethyl-3-butenyl 2,2-Dimethyl-3-butenyl, 2,3-Dimethyl-1-butenyl, 2,3-Dimethyl-2-butenyl, 2,3-Dimethyl-3-butenyl, 3,3-Dimethyl-1-butenyl, 3,3-Dimethyl-2-butenyl, 1-Ethyl-1-butenyl, 1-Ethyl-2-butenyl, 1-Ethyl-3-butenyl, 2-Ethyl-1-butenyl, 2-Ethyl-2-butenyl, 2-Ethyl-3-butenyl, 1,1,2-Trimethyl-2-propenyl, 1-Ethyl-1-methyl-2-propenyl, 1-Ethyl-2-methyl-1-propenyl and 1-Ethyl-2-methyl-2-propenyl.

[0102] An alkynyl group refers to a straight-chain or branched hydrocarbon group that has a specified number of carbon atoms and a triple bond at any position in each case, such as C2-C6-alkynyl groups, including ethynyl, 1-propynyl, 2-propynyl (or propynyl), 1-butynyl, 2-butynyl, 3-butynyl, 1-methyl-2-propynyl, 1-pentynyl, 2-pentynyl, 3-pentynyl, 4-pentynyl, 3-methyl-1-butynyl, 1-methyl-2-butynyl, 1-methyl-3-butynyl, 2-methyl-3-butynyl, 1,1-dimethyl-2-propynyl, 1-ethyl-2-propynyl, 1-hexynyl, 2-hexynyl, 3-hexynyl, 4-hexynyl, 5- Hexynyl, 3-methyl-1-pentynyl, 4-methyl-1-pentynyl, 1-methyl-2-pentynyl, 4-methyl-2-pentynyl, 1-methyl-3-pentynyl, 2-methyl-3-pentynyl, 1-methyl-4-pentynyl, 2-methyl-4-pentynyl, 3-methyl-4-pentynyl, 1,1-dimethyl-2-butynyl, 1,1-dimethyl-3-butynyl, 1,2-dimethyl-3-butynyl, 2,2-dimethyl-3-butynyl, 3,3-dimethyl-1-butynyl, 1-ethyl-2-butynyl, 1-ethyl-3-butynyl, 2-ethyl-3-butynyl and 1-ethyl-1-methyl-2-propynyl.

[0103] Cycloalkyl refers to a carbocyclic saturated ring system having preferably 3-8 ring carbon atoms, such as cyclopropyl, cyclobutyl, cyclopentyl, or cyclohexyl. In the case of optionally substituted cycloalkyl, it includes cyclic systems with substituents, and also includes substituents having a double bond on the cycloalkyl group, such as alkylene groups, like methylene groups.

[0104] In the case of optionally substituted cycloalkyl groups, polycyclic aliphatic systems are also included, such as bicyclo[1.1.0]but-1-yl, bicyclo[1.1.0]but-2-yl, bicyclo[2.1.0]pent-1-yl, bicyclo[2.1.0]pent-2-yl, bicyclo[2.1.0]pent-5-yl, bicyclo[2.2.1]hept-2-yl (norkenyl), adamantane-1-yl, and adamantane-2-yl.

[0105] In the case of substituted cycloalkyl groups, spirocycloaliphatic systems are also included, such as spiro[2.2]pent-1-yl, spiro[2.3]hex-1-yl, spiro[2.3]hex-4-yl, and 3-spiro[2.3]hex-5-yl.

[0106] Cycloalkenyl refers to a partially unsaturated, non-aromatic cyclic system having preferably 4-8 carbon atoms, such as 1-cyclobutenyl, 2-cyclobutenyl, 1-cyclopentenyl, 2-cyclopentenyl, 3-cyclopentenyl, or 1-cyclohexenyl, 2-cyclohexenyl, 3-cyclohexenyl, 1,3-cyclohexadienyl, or 1,4-cyclohexadienyl, and also includes substituents having a double bond on the cycloalkenyl group, such as alkylene groups, like methylene groups. In the case of optionally substituted cycloalkenyl groups, the description corresponding to substituted cycloalkyl groups applies accordingly.

[0107] Alkoxy refers to a saturated straight-chain or branched alkoxy group having a specified number of carbon atoms in each case, such as C1-C6-alkoxy groups, including methoxy, ethoxy, propoxy, 1-methylethoxy, butoxy, 1-methylpropoxy, 2-methylpropoxy, 1,1-dimethylethoxy, pentoxy, 1-methylbutoxy, 2-methylbutoxy, 3-methylbutoxy, 2,2-dimethylpropoxy, 1-ethylpropoxy, hexoxy, 1,1-dimethylpropoxy, and 1,2-dimethylpropoxy. The compounds are: 1-methylpentoxy, 2-methylpentoxy, 3-methylpentoxy, 4-methylpentoxy, 1,1-dimethylbutoxy, 1,2-dimethylbutoxy, 1,3-dimethylbutoxy, 2,2-dimethylbutoxy, 2,3-dimethylbutoxy, 3,3-dimethylbutoxy, 1-ethylbutoxy, 2-ethylbutoxy, 1,1,2-trimethylpropoxy, 1,2,2-trimethylpropoxy, 1-ethyl-1-methylpropoxy, and 1-ethyl-2-methylpropoxy. Halogen-substituted alkoxy groups refer to the following straight-chain or branched alkoxy groups having a specified number of carbon atoms in each case: wherein in these groups, some or all of the hydrogen atoms may be replaced by halogen atoms as described above, such as C1-C2-haloalkoxy groups, including chloromethoxy, bromomethoxy, dichloromethoxy, trichloromethoxy, fluoromethoxy, difluoromethoxy, trifluoromethoxy, chlorofluoromethoxy, dichlorofluoromethoxy, chlorodifluoromethoxy, 1-chloroethoxy, 1-bromoethoxy, 1-fluoroethoxy, 2-fluoroethoxy, 2,2-difluoroethoxy, 2,2,2-trifluoroethoxy, 2-chloro-2-fluoroethoxy, 2-chloro-2,2-difluoroethoxy, 2,2,2-dichloro-2-fluoroethoxy, 2,2,2-trichloroethoxy, pentafluoroethoxy, and 1,1,1-trifluoroprop-2-oxy.

[0108] Aromatic refers to a phenyl group that is optionally substituted with 0 to 5 groups selected from the following groups: fluorine, chlorine, bromine, iodine, cyano, hydroxyl, C1-C3-alkyl, C1-C3-alkoxy, C3-C4-cycloalkyl, C2-C3-alkenyl, and C2-C3-ynyl.

[0109] The term "halogen" refers to fluorine, chlorine, bromine, or iodine. If the term is used with a group, then "halogen" refers to a fluorine, chlorine, bromine, or iodine atom.

[0110] Depending on the nature and linkage of the substituents, compounds of formula (I) can exist as stereoisomers. For example, enantiomers and diastereomers may occur when one or more asymmetrically substituted carbon atoms and / or sulfoxides are present. Stereoisomers can be obtained from the mixture obtained during the preparation process using conventional separation methods, such as chromatographic separation. Similarly, stereoisomers can be selectively prepared by using optically active raw materials and / or auxiliaries in a stereoselective reaction.

[0111] The present invention also relates to all stereoisomers covered by but not specifically defined by formula (I) and mixtures thereof. However, for simplicity, the compounds of formula (I) will always be referred to below, although this should be understood to mean not only the pure compounds, but also, where appropriate, mixtures of isomeric compounds in different amounts.

[0112] Based on the properties of the substituents defined above, compounds of formula (I) are acidic and can form salts, and if suitable, can also form internal salts, or form adducts with inorganic or organic bases or with metal ions. If compounds of formula (I) contain a hydroxyl group, a carboxyl group, or other groups that cause acidity, these compounds can react with a base to form a salt. Suitable bases are, for example, hydroxides, carbonates, and bicarbonates of alkali metals and alkaline earth metals, particularly sodium, potassium, magnesium, and calcium; and ammonia; primary, secondary, and tertiary amines having C1-C4-alkyl groups; monoalkylolamines, dialkylolamines, and trialkylolamines of C1-C4-alkanols; choline and choline chloride; and organic amines such as trialkylamines, morpholine, piperidine, or pyridine. These salts are compounds in which the acidic hydrogen is replaced by an agriculturally suitable cation, for example, metal salts, especially alkali metal or alkaline earth metal salts, especially sodium and potassium salts; or ammonium salts, organic amine salts, or quaternary ammonium salts, for example having the formula [NRR′R″R″′]. + Salts of cations (where R to R″′ each independently represents an organic group, particularly alkyl, aryl, aralkyl, or alkylaryl). Also suitable are alkyl sulfonium salts and alkyl oxide sulfonium salts, such as C1-C4-trialkyl sulfonium salts and C1-C4-trialkyl oxide sulfonium salts.

[0113] Compounds of formula (I) can be formed into salts by adding a suitable inorganic or organic acid to a basic group; the inorganic acid being, for example, HCl, HBr, H₂SO₄, H₃PO₄, or HNO₃; the organic acid being, for example, a carboxylic acid (e.g., formic acid, acetic acid, propionic acid, oxalic acid, lactic acid, or salicylic acid) or a sulfonic acid (e.g., p-toluenesulfonic acid); and the basic group being, for example, an amino, alkylamino, dialkylamino, piperidinyl, morpholinyl, or pyridinyl group. In this case, the salts contain the conjugate base of the acid as an anion.

[0114] Suitable substituents (e.g., sulfonic acids or carboxylic acids) in deprotonated form can form internal salts with groups that are themselves protonable (e.g., amino groups).

[0115] If a group is substituted by multiple groups, it means that the group is substituted by one or more of the same or different groups mentioned above.

[0116] In all formulas specified below, unless otherwise defined, substituents and symbols have the same meaning as described in formula (I). Arrows in chemical formulas indicate sites attached to the rest of the molecule.

[0117] The following describes the definitions of preferred, particularly preferred, and very particularly preferred for each substituent. Other substituents of general formula (I) not specified below have the definitions given above.

[0118] Examples of compounds of general formula (I) are shown in tabular form below. Table 1 below lists the substituents in formula (I) as defined in general terms.

[0119] Table 1 shows the compounds of formula (I).

[0120] The compounds of the present invention can be prepared by the various methods listed below:

[0121] Route 1:

[0122] In routes 1 and below, the definitions of each substituent are the same as above. The 1,3-dipolar cycloaddition of such nitrile oxides with suitable dipolarophiles is described, for example, in the following reviews: 1,3 dipolar Cycloaddition Chemistry, edited by Padwa, Wiley, New York, 1984; Kanemasa and Tsuge, Heterocycles 1990, 30, 719. For the preparation of chlorooximes, see Kim, Jae N., Ryu, Eung K. J. Org. Chem. 1992, 57, 6649.

[0123] The compounds of the present invention with substituted 4- and 5-positions in the isoxazoline ring system can also be prepared by 1,3-dipolar cycloaddition using a suitable 1,2-disubstituted olefin as a dipolarophile. Typically, this reaction yields a mixture of diastereomers, which can be separated by column chromatography. Optically active isoxazolines can be obtained by chiral HPLC of suitable precursors or final products, or by enantioselective reactions (e.g., enzymatic esterification or amide cleavage), or by using a chiral auxiliary on the dipolarophile, as described by Olssen (J. Org. Chem. 1988, 53, 2468). Suitable substituted acrylamides (route 3) can also be used to prepare the compounds of the present invention. These can be obtained from the acrylates described in route 2 after hydrolysis and amide formation.

[0124] Route 2:

[0125] One option for activating acrylic acid is a carbodiimide, such as EDCI (Chen, FMF; Benoiton, NLSynthesis 1979, 709). For the preparation of acrylamides, see US 2,521,902, JP 60112746, J. of Polymer Science 1979, 17(6), 1655. Appropriately substituted acrylamides can be reacted with α-chlorooxime compounds via a 1,3-cycloaddition reaction to yield the compounds of this invention (route 3).

[0126] Route 3:

[0127] The conversion of functional group R3 can be carried out in the olefin stage or the isoxazoline stage.

[0128] The compounds of formula (I) synthesized by the above reactions and / or collections of their salts can also be prepared in parallel, in which case the process can be carried out manually, semi-automatically, or fully automatically. For example, the post-processing or purification of the reaction, products, and / or intermediates can be automated. In summary, this should be understood to mean, for example, the steps described by D. Tiebes in Combinatorial Chemistry-Synthesis, Analysis, Screening, Wiley, 1999, pp. 1-34.

[0129] The compounds of formula (I) of the present invention (and / or their salts) – hereinafter collectively referred to as “compounds of the present invention” – exhibit excellent herbicidal efficacy against a broad spectrum of economically important monocotyledonous and dicotyledonous annual pests. They can effectively control a variety of weeds, achieving good results at low doses, and can be used as herbicides. Therefore, the present invention also includes the use of compounds of formula (I) for weed control.

[0130] Therefore, this invention relates to a method for controlling unwanted plants or for regulating plant growth, wherein one or more compounds of the invention are applied to plants (e.g., harmful plants, such as monocot or dicot weeds or unwanted crop plants), seeds (e.g., grains, seeds, or asexual propagules, such as tubers or budding young shoots), or plant growing areas (e.g., cultivated areas). The compounds of the invention can be applied before planting (and, if appropriate, by introduction into the soil), pre-emergence, or post-emergence. The various representative monocot and dicot weed populations controlled by the compounds of the invention mentioned below are merely illustrative of the invention and are by no means limiting of the invention.

[0131] Monocotyledonous harmful plant genera: *Aegilops*, *Agropyron*, *Agrostis*, *Alopecurus*, *Apera*, *Avena*, *Brachiaria*, *Bromus*, *Cenchrus*, *Commelina*, *Cynodon*, *Cyperus*, *Dactyloctenium*, *Digitaria*, *Echinochloa*, *Eleocharis*, *Eleusine*, *Eragrostis*, *Sorghum* (Eriochloa), Festuca, Fimbristylis, Heteranthera, Imperata, Ischaemum, Leptochloa, Lolium, Monochooria, Panicum, Paspalum, Phalaris, Phleum, Poa, Rottboellia, Sagittaria, Scirpus, Setaria, Sorghum.

[0132] Dicotyledonous weeds: *Abutilon*, *Amaranthus*, *Ambrosia*, *Anoda*, *Anthemis*, *Aphanes*, *Artemisia*, *Atriplex*, *Bellis*, *Bidens*, *Capsella*, *Carduus*, *Cassia*, *Centaurea*, *Chenopodium*, *Cirsium* Convolvulus, Datura, Desmodium, Emex, Erysimum, Euphorbia, Galeopsis, Galinsoga, Galium, Hibiscus, Ipomoea, Kochia, Lamium, Lepidium, Lindernia, Motherwort *Matricaria*, *Mentha*, *Mercurialis*, *Mullugo*, *Myosotis*, *Papaver*, *Pharbitis*, *Plantago*, *Polygonum*, *Portulaca*, *Ranunculus*, *Raphanus*, *Rorippa*, *Rotala*, *Rumex*, *Saussurea* The genera *Lysola*, *Senecio*, *Sesbania*, *Sida*, *Sinapis*, *Solanum*, *Sonchus*, *Sphenoclea*, *Stellaria*, *Taraxacum*, *Thlaspi*, *Trifolium*, *Urtica*, *Veronica*, *Viola*, and *Xanthium*.

[0133] When the compounds of this invention are applied to the soil pre-emergence, harmful plant seeds stop growing after treatment, and the harmful plants remain in the growth stage at the time of application or die completely after a certain period of time, thereby eliminating competition from harmful weeds for crop plants in a lasting manner at a very early time.

[0134] When the compounds of this invention are applied to the green parts of plants post-emergence, growth ceases after treatment, and harmful plants remain in their growth period at the time of application or die completely after a certain period of time, thereby eliminating competition from harmful weeds for crops in a sustained manner at a very early time.

[0135] The compounds of the present invention can be selective in crops with useful plants, and can also be used as non-selective herbicides.

[0136] Therefore, the technical solution of the present invention also includes the use of compounds of general formula (I) for controlling weeds.

[0137] Furthermore, the compounds of general formula (I) of this invention are also applicable to the drying and / or defoliation of plants.

[0138] As mentioned above, the present invention provides a pesticide herbicide composed of an active ingredient and excipients, wherein the active ingredient includes at least one of the aforementioned 3-phenylisooxazoline-5-carboxamide compounds.

[0139] In a preferred embodiment, the active ingredient in the pesticide herbicide is present in an amount of 0.1-99.9% by weight.

[0140] The present invention does not impose any particular limitation on the specific types of excipients in the herbicide, such as various surfactants and solvents commonly used in the field of herbicides.

[0141] The compounds of the present invention can be applied using common formulations, including wettable powders, concentrated emulsions, sprayable solutions, powders, or granules. Thus, the present invention also provides herbicide compositions comprising compounds of formula (I). Compounds of formula (I) can be formulated in various ways depending on typical biological and / or chemical physical parameters. Examples of suitable formulation choices include: wettable powders (WP), water-soluble powders (SP), water-soluble concentrates, concentrated emulsions (EC), emulsions such as oil dispersed in water and water dispersed in oil (EW), sprayable solutions, suspension concentrates (SC), dispersible oil suspensions (OD), suspensions diluted with oil or water, solutions miscible with oil, powders (DP), capsule suspensions (CS), seeddressing compositions, granules for broadcasting and soil application, spray granules, coating granules and absorbent granules, water-dispersible granules (WG), water-soluble granules (SG), ULV (ultra-low volume) formulations, microcapsules, and wax products. These individual formulation types are known and described in the following literature, for example, Winnacker-Küchler, Chemical Processes, Vol. 7, C. Hauser Verlag Munich, 4th ed. 1986; Wade van Valkenburg, “Pesticide Formulations”, Marcel Dekker, NY, 1973; K. Martens, “Spray Drying” Handbook, 3rd ed. 1979, G. Goodwin Ltd. London.

[0142] Necessary formulation adjuvants, such as inert substances, surfactants, solvents, and other additives, are also known and described in the following documents, for example: Watkins, Handbook of Powder Diluents, Insecticides and Carriers, 2nd ed., Darland Caldwell NJ; Hv01phen, Introduction to Clay Colloid Chemistry, 2nd ed., J. Wiley and Sons, NY; C. Marsden, Solvent Guide, 2nd ed., Interscience, NY 1963; McCutcheon, Annual Report on Detergents and Emulsifiers, MC Publishing Company, Ridgewood NJ; Sisley and Wood, Encyclopedia of Surfactants, Chemical Publishing Company, NY 1964; Ethylene Oxide Addition Surfactants, Wiss. Verlagagesell. Stuttgart 1976; Winnacker-Küchler, Chemical Processes, Vol. 7, C. Hauser Verlag Munich, 4th ed., 1986.

[0143] Wettable powders are uniformly dispersible in water and, in addition to the active ingredient, include diluents or inert substances, ionic and nonionic surfactants (wetting agents, dispersants), such as polyethoxyalkylphenols, polyethoxy fatty alcohols, polyoxyethyl aliphatic amines, fatty alcohol polyethylene glycol ether sulfates, alkyl sulfonates, alkyl phenyl sulfonates, sodium lignosulfonate, sodium 2,2'-dinaphthylmethane-6,6'-disulfonate, sodium dibutylnaphthalenesulfonate, or sodium oleoylmethyl taurate. To prepare wettable powders, the active ingredient of the herbicide is finely ground, for example using common equipment such as hammer mills, fan mills, and jet mills, while adjuvants are mixed in simultaneously or sequentially.

[0144] Concentrated emulsions are prepared by dissolving active ingredients in an organic solvent, such as butanol, cyclohexanone, dimethylformamide, xylene, or a mixture of higher-boiling aromatic compounds or hydrocarbons, and then adding one or more ionic and / or nonionic surfactants (emulsifiers). Examples of emulsifiers that can be used include, for example, calcium alkylaryl sulfonate of calcium dodecylbenzenesulfonate, or nonionic emulsifiers such as fatty acid polyethylene glycol esters, alkyl aromatic polyethylene glycol ethers, fatty alcohol polyethylene glycol ethers, propylene oxide-ethylene oxide condensation products, alkyl polyethers, sorbitan esters such as sorbitan fatty acid esters, or polyethylene oxide sorbitan esters such as polyethylene oxide sorbitan fatty acid esters.

[0145] The active substance and finely ground solid material are ground to obtain a powder. The solid material may be talc, natural clay such as kaolin, bentonite, and pyrophyllite, or diatomaceous earth. A water- or oil-based suspension may be prepared, for example, by wet grinding using a commercially available glass bead mill, with or without the addition of a surfactant of the other formulation type mentioned above.

[0146] Emulsions, such as oil-in-water (EW) emulsions, can be prepared using an aqueous organic solvent, a stirrer, a colloid mill, and / or a static mixer, and if necessary, by adding a surfactant of another formulation type as described above.

[0147] Granules can be prepared by spraying the active material onto an adsorbent and granulating it using an inert material, or by concentrating the active material onto the surface of a carrier such as sand or kaolinite and granulating it using a binder such as polyvinyl alcohol, sodium polyacrylate, or mineral oil. Suitable active materials can be granulated using methods for preparing fertilizer granules, and fertilizers can be mixed in if necessary. Aqueous suspension granules can be prepared using conventional methods such as spray-drying, fluidized bed granulation, disc granulation, mixing using a high-speed mixer, and extrusion without solid inert material.

[0148] For methods of preparing granules using milling discs, fluidized beds, extruders, and spraying, see the following processes, for example, “Spray Drying Handbook,” 3rd edition, 1979, G. Goodwin Ltd., London; J.E. Browning, “Agglomeration,” Chemicals and Engineering, 1967, 147ff; “Perry’s Chemical Engineer’s Handbook,” 5th edition, McGraw-Hill, New York, 1973, 8–57. For information on formulations of crop protection products, see, for example, G.K. C. Lingman, “Weed Control as a Science,” John Wiley and Sons, New York, 1961, 81–96; and JD. F. Greyer, SAEvans, “Weed Control Handbook,” 5th edition, Blackwell Scientific Rublications, Oxford University Press, 1968, 101–103.

[0149] Agricultural chemical formulations typically contain 0.1% to 99%, particularly 0.1% to 95%, of active ingredient (I) by weight. The concentration of active ingredient in wettable powders is, for example, from about 10% to 99% by weight, with the usual formulation components constituting the remainder to 100% by weight. The concentration of active ingredient in concentrated emulsions can be from about 1% to 90% by weight, preferably 5% to 80%. Powder formulations contain 1% to 30% active ingredient by weight, typically preferably 5% to 20% by weight; however, sprayable solutions contain about 0.05% to 80% by weight, preferably 2% to 50% by weight. The content of active ingredient in aqueous suspension granules depends primarily on whether the active ingredient is liquid or solid, and on the adjuvants, fillers, etc., used during granulation. The content of active ingredient in aqueous suspension granules is, for example, between 1% and 95% by weight, preferably between 10% and 80% by weight.

[0150] The formulation of the active substance may also include thickeners, wetting agents, dispersants, emulsifiers, penetrants, preservatives, antifreeze agents, solvents, fillers, carriers, colorants, defoamers, evaporation inhibitors, and pH and viscosity adjusters that are commonly used in all cases.

[0151] Based on these formulations, they may also be mixed with other insecticidal active substances such as insecticides, acaricides, herbicides and fungicides, or with safeners, fertilizers and / or plant growth regulators. The mixing method may be pre-mixed or bottled.

[0152] For application, commercially available formulations are diluted in a conventional manner, if appropriate, such as with water in the case of wettable powders, emulsifiable concentrates, dispersants, and water-dispersible granules. Powder formulations, granules for soil application or broadcasting, and sprayable solutions are generally not further diluted with other inert substances before application.

[0153] The required application rate of the compound of formula (I) varies depending on external conditions, including, in particular, temperature, humidity and the type of herbicide used. The application rate can vary over a wide range, for example, from 0.001 to 1.0 kg / ha or more of active substance, but is preferably from 0.005 to 750 g / ha.

[0154] The carrier is a natural or synthetic organic or inorganic substance that is mixed or combined with an active compound for better application, particularly to plants, plant parts, or seeds. The carrier (which may be solid or liquid) is typically inert and should be suitable for agricultural applications.

[0155] Useful solid or liquid carriers include, for example, ammonium salts and natural rock powders such as kaolin, clay, talc, chalk, quartz, palygorskite, montmorillonite, or diatomaceous earth; and synthetic rock powders such as finely dispersed silica, alumina, and natural or synthetic silicates, resins, waxes, and solid fertilizers; water; alcohols, especially butanol; organic solvents, mineral oils, and vegetable oils, and their derivatives. Mixtures of the aforementioned carriers may also be used. Useful solid carriers for granules include, for example, pulverized and graded natural rocks such as calcite, marble, pumice, sepiolite, and dolomite; and synthetic granules of inorganic and organic powders; as well as granules of organic materials such as sawdust, coconut husks, corn cobs, and tobacco stalks.

[0156] Suitable liquefied gas extenders or carriers are liquids that are gaseous at standard temperature and atmospheric pressure, such as aerosol propellants, like halogenated hydrocarbons, or butane, propane, nitrogen, and carbon dioxide.

[0157] In the formulation, thickeners such as carboxymethyl cellulose may be used; natural and synthetic polymers in powder, granule, or latex form, such as gum arabic, polyvinyl alcohol, and polyvinyl acetate; or natural phospholipids such as cephalin and lecithin, as well as synthetic phospholipids. Other additives may be mineral oils and vegetable oils.

[0158] If the extender used is water, organic solvents, for example, can also be used as co-solvents. Suitable liquid solvents include: aromatic compounds such as xylene, toluene, or alkylnaphthalene; chlorinated aromatic compounds and chlorinated aliphatic hydrocarbons such as chlorobenzene, vinyl chloride, or dichloromethane; aliphatic hydrocarbons such as cyclohexane or paraffins such as mineral oil fractions, mineral oil, and vegetable oils; alcohols such as butanol or ethylene glycol and their ethers and esters; ketones such as acetone, methyl ethyl ketone, methyl isobutyl ketone, or cyclohexanone; highly polar solvents such as dimethylformamide and dimethyl sulfoxide; and water.

[0159] The compositions of the present invention may also contain other components, such as surfactants. Useful surfactants are emulsifiers and / or foaming agents, dispersants, or wetting agents, or mixtures of these surfactants, having ionic or nonionic properties. Examples of them are polyacrylates; lignin sulfonates; salts of phenolic sulfonic acids or naphthalene sulfonic acids; condensates of ethylene oxide with fatty alcohols or with fatty acids or with fatty amines; substituted phenols (preferably alkylphenols or arylphenols); salts of sulfosuccinates; taurine derivatives (preferably alkyl taurine esters); phosphate esters of polyethoxylated alcohols or phenols; fatty acid esters of polyols; and derivatives of compounds containing sulfate, sulfonate, and phosphate groups, such as alkylaryl polyethylene glycol ethers, alkyl sulfonates, alkyl sulfates, aryl sulfonates, protein hydrolysates, sulfite pulp waste liquor, and methylcellulose. A surfactant must be present if one of the active compounds and / or one of the inert carriers is insoluble in water and is applied in water. The surfactant is present in proportions of 5 to 40% by weight of the compositions of the present invention. Dyes, such as inorganic pigments like iron oxide, titanium dioxide, and Prussian blue, as well as organic dyes like alizarin dyes, azo dyes, and metal phthalocyanine dyes, and micronutrients such as iron salts, manganese salts, boron salts, copper salts, cobalt salts, molybdenum salts, and zinc salts, can be used.

[0160] Other additional components may be present, if appropriate, such as protective colloids, binders, adhesives, thickeners, thixotropic substances, penetrants, stabilizers, chelating agents, and complexing agents. Typically, the active compound can be combined with any solid or liquid additive commonly used for formulation purposes. Typically, the compositions and formulations of the present invention contain 0.05 to 99% by weight, 0.01 to 98% by weight, preferably 0.1 to 95% by weight, more preferably 0.5 to 90% by weight, and most preferably 10 to 70% by weight of the active compound. The active compounds or compositions of the present invention may be used in their own form or, depending on their respective physical and / or chemical properties, in the form of formulations or in the form of formulations, such as aerosols, capsule suspensions, cold fog concentrates, warm fog concentrates, capsule granules, fine granules, flowable concentrates for seed treatment, ready-to-use solutions, spreadable powders, emulsifiable concentrates, oil-in-water emulsions, water-in-oil emulsions, large granules, microgranules, oil-dispersible powders, oil-miscible flowable concentrates, oil-miscible liquids, foaming agents, pastes, pesticide-coated seed, suspension concentrates, emulsion concentrates, soluble concentrates, suspensions, wettable powders, soluble powders, dusts and granules, water-soluble granules or tablets, water-soluble powders for seed treatment, wettable powders, natural and synthetic substances impregnated with active compounds, as well as microcapsules in polymeric substances and seed coating materials, and ULV cold fog and warm fog formulations.

[0161] The formulation can be prepared in a manner known per se, for example by mixing the active compound with at least one conventional substance including: a extender, solvent or diluent, emulsifier, dispersant and / or binder or fixative, wetting agent, waterproofing agent, optionally a drying agent and UV stabilizer, and optionally dyes and pigments, defoamers, preservatives, secondary thickeners, viscous agents, gibberellins and other processing aids.

[0162] The compositions of the present invention include not only preparations that are ready for use and can be applied to plants or seeds using suitable equipment, but also commercially available concentrates that must be diluted with water before use.

[0163] The active compounds of the present invention may exist in their own form, or in a (commercial standard) formulation thereof, or in a form prepared by mixing such formulations with other (known) active compounds, such as insecticides, attractants, reproductive inhibitors, bactericides, acaricides, nematicides, fungicides, growth regulators, herbicides, fertilizers, safety agents, or chemical pheromones.

[0164] The treatment of plants and plant parts using active compounds or compositions of the present invention is carried out directly using conventional treatment methods or by acting on their environment, habitat, or storage space, such as by soaking, spraying, atomizing, irrigation, evaporation, dusting, fogging, broadcasting, foaming, coating, spreading, watering (wetting), drip irrigation, and in the case of propagation materials, especially seeds, dry seed treatment with powder, seed treatment with solution, slurry treatment with water-soluble powder, treatment by shelling, coating with one or more layers, etc. Active compounds can also be applied by ultra-low volume methods, or the active compound formulation or the active compound itself can be injected into the soil.

[0165] To enhance the control effect of the 3-phenylisooxazoline-5-carboxamide compounds of this invention and expand their application scope, the 3-phenylisooxazoline-5-carboxamide compounds of this invention can be used alone or in combination with other commonly used herbicides. Moreover, there is no particular limitation on the ratio of the combination, which can be selected according to the ratio conventionally used in the art, as long as the control effect, application scope and safety can be improved after combination.

[0166] Suitable active substances that can be mixed with the active substances of the present invention in compound formulations or tank-mixed formulations include, for example, known substances in the "World Encyclopedia of New Pesticide Varieties Technology", China Agricultural Science and Technology Press, 2010.9 and the literature cited herein.

[0167] Examples of safeners include benoxacor, cloquintocet, cloquintocet-mexyl, cumyluron, cyometrinil, cyprosulfamide, daimuron (dymron), dichlormid, dicyclonon (diclonon), dietholate, dimepiperate, and disulphoton. Fenchlorazole, fenchlorazole-ethyl, fenclorim, flurazole, fluxofenim, furilazole, isoxadifen, isoxadifen-ethyl, mefenpyr, mefenpyr-diethyl, mephenate, methoxyphenone, naphthalic anhydride anhydride, NA), octamethylene-diamine, oxabetrinil, metcamifen, 4-(dichloroacetyl)-1-oxa-4-azaspiro[4.5]decane (AD67, MON4660), 4-carboxy-3,4-dihydro-2H-1-benzopyran-4-acetic acid (CL304415), 2,2-dichloro-N-[2-oxo-2-(propenylamino)ethyl]-N-2-propenylacetamide (DKA-24), 2-(dichloromethyl)-2-methyl-1,3-dioxolane (MG191), 2-propenyl-1-oxa-4 The following are some of the ingredients: azirospiro[4,5]decane-4-dithiocarbamate (MG838), (3-dichloroacetyl-5-(2-furanyl)-2,2-dimethylazolidine (MON13900), (N-allyl-N-[(1,3-dioxolane-2-yl)methyl]dichloroacetamide (PPG-1292), 3-(dichloroacetyl)-2,2-dimethyl-1,3-azolidine (R28725), 3-(dichloroacetyl)-2,2,5-trimethyl-1,3-azolidine (R29148), and 1-dichloroacetylaziroheptanane (TI-35). These ingredients can be used alone or in mixtures of two or more, and the ratio of these mixtures can be freely chosen.

[0168] As described below, it is also particularly important to treat transgenic seeds with the active compounds or compositions of the present invention. This involves seeds of plants containing at least one heterologous gene capable of expressing a polypeptide or protein with insecticidal properties. The heterologous gene in the transgenic seed may be derived from microorganisms such as Bacillus, Rhizobium, Pseudomonas, Serratia, Trichoderma, Clavibacter, Glomus, or Gliocladium. This heterologous gene is preferably derived from Bacillus, in which case the gene product is effective against the European corn borer and / or the western corn rootworm. More preferably, the heterologous gene is derived from Bacillus thuringiensis.

[0169] In the context of this invention, the compositions of the invention are applied to seeds alone or in a suitable formulation. Preferably, the seeds are treated in a sufficiently stable state to prevent damage during treatment. Generally, the seeds can be treated at any time between harvesting and sowing. Seeds that have been separated from the plant and whose rachis, husk, stem, chrysanthemum, hairs, or pulp have been removed are typically used. For example, seeds that have been harvested, cleaned, and dried to a moisture content of less than 15% by weight can be used. Alternatively, seeds that have been dried, for example, treated with water and then dried again can also be used.

[0170] When treating seeds, it is generally necessary to ensure that the amount of the compositions of the present invention and / or other additives applied to the seeds is selected so as not to impair seed germination and the resulting plants. This must be ensured, especially in the case of active compounds that may have phytotoxic effects at certain application rates.

[0171] The compositions of the present invention can be applied directly, i.e., without any other components and without dilution. Generally, it is preferred to apply the compositions to seeds in a suitable formulation. Suitable formulations and methods for seed treatment are known to those skilled in the art and are described in the following documents: for example, US4,272,417A, US4,245,432A, US4,808,430, US5,876,739, US2003 / 0176428A1, WO2002 / 080675A1, WO2002 / 028186A2.

[0172] The active compounds that can be used according to the present invention can be converted into conventional seed coating formulations, such as solutions, emulsions, suspensions, powders, foams, slurries or other seed coating compositions, as well as ULV formulations.

[0173] These formulations are prepared in a known manner by mixing an active compound with conventional additives, such as conventional extenders, solvents or diluents, dyes, wetting agents, dispersants, emulsifiers, defoamers, preservatives, secondary thickeners, adhesives, gibberellins, and water. The dyes that may be present in the seed dressing formulations usable according to the invention are all dyes commonly used for this purpose.

[0174] Pigments that are slightly soluble in water or dyes that are soluble in water can be used. Examples include dyes known as Rhodamine B, CI Pigment Red, and CI Solvent Red 1.

[0175] Useful wetting agents that can be present in seed dressing formulations used according to the present invention are all substances that promote wetting and are commonly used in the formulation of agrochemically active compounds. Alkyl naphthalene sulfonates, such as diisopropyl naphthalene sulfonate or diisobutyl naphthalene sulfonate, are preferred.

[0176] Suitable dispersants and / or emulsifiers that may be present in seed dressing formulations usable according to the present invention are all nonionic, anionic, and cationic dispersants commonly used in the formulation of agrochemically active compounds. Nonionic or anionic dispersants, or mixtures of nonionic or anionic dispersants, are preferred. Suitable nonionic dispersants particularly include ethylene oxide / propylene oxide block polymers, alkylphenol polyethylene glycol ethers, and tristyrylphenol polyethylene glycol ethers, and their phosphorylated or sulfated derivatives. Suitable anionic dispersants particularly include lignin sulfonates, polyacrylates, and aryl sulfonate-formaldehyde condensates.

[0177] The defoamer that may be present in the seed dressing formulations used according to the present invention is any foam-inhibiting substance commonly used in the formulation of agrochemically active compounds. Silicone defoamers and magnesium stearate are preferred.

[0178] Preservatives that may be present in seed dressing formulations that can be used according to the present invention are all substances that can be used for this purpose in agricultural chemical compositions. Examples include dichlorophenol and benzyl alcohol hemiacetal.

[0179] The secondary thickener that may be present in the seed dressing formulations used according to the present invention is any substance that can be used for this purpose in agricultural chemical compositions. Preferred examples include cellulose derivatives, acrylic acid derivatives, xanthan gum, modified clay, and finely dispersed silica.

[0180] Useful adhesives that can be present in seed dressing formulations that can be used according to the invention are all conventional adhesives that can be used in seed dressing products. Preferred examples include polyvinylpyrrolidone, polyvinyl acetate, polyvinyl alcohol, and tylose.

[0181] The seed dressing formulations used according to the present invention can be used directly or after pre-diluting with water to treat various types of seeds (including seeds of transgenic plants). In this case, additional synergistic effects will occur in the interaction with substances formed through expression.

[0182] For treating seeds with a seed dressing formulation applicable according to the present invention, or a formulation prepared therefrom by adding water, useful equipment includes all mixing devices conventionally used for seed dressing. Specifically, the seed dressing process involves: placing the seeds in a mixer; adding a specific desired amount of the seed dressing formulation (either on its own or after pre-diluting with water); and mixing them until the formulation is evenly distributed on the seeds. If appropriate, a drying process is then performed.

[0183] Because the active compounds of this invention have good plant compatibility, good homeothermic animal toxicity and good environmental compatibility, they are suitable for protecting plants and plant organs, increasing harvest yield and improving the quality of harvested crops.

[0184] They can be preferred as crop protectants. They are active in both generally sensitive and resistant species and at all or specific developmental stages.

[0185] The plants that can be treated according to the present invention include the following major crop plants: corn, soybean, cotton, rapeseed (Brassica oilseeds) such as Brassica napus (e.g., Canada canola), turnip (Brassica rapa), mustard-type rapeseed (B. juncea) (e.g., wild mustard) and Ethiopian mustard (Brassica carinata), rice, wheat, sugar beets, sugarcane, oats, rye, barley, millet and sorghum, triticale, flax, vines, and various fruits and vegetables from various plant taxa, such as species of Rosaceae (e.g., pome fruits such as apples and pears, and drupes such as apricots, cherries, almonds and peaches, and berries such as strawberries), species of Ribesioidae, species of Juglandaceae, species of Betulaceae, species of Anacardiaceae, and species of Fagaceae. species of the following families: Moraceae (sp.), Oleaceae (sp.), Actinidaceae (sp.), Lauraceae (sp.), Musaceae (sp.) (e.g., banana and plantain), Rubiaceae (sp.) (e.g., coffee), Theaceae (sp.), Sterculiaceae (sp.), Rutaceae (sp.) (e.g., lemon, orange, and grapefruit), Solanaceae (sp.) (e.g., tomato, potato, pepper, eggplant), Liliaceae (sp.), and Compositiae (sp.) (e.g., lettuce, artichoke, and chicory—including root chicory, endive, or common chicory). Chicory), umbelliferae (e.g., carrots, parsley, celery, and root celery), Cucurbitaceae (e.g., cucumbers—including gherkin, squash, watermelon, cucurbits, and melons), Alliaceae (e.g., onions and leeks), and Cruciferae (e.g., cruciferous plants).(e.g., white cabbage, red cabbage, broccoli, cauliflower, Brussels sprout, pak choi, kohlrabi, radish, wasabi, cress, Chinese cabbage); Leguminosae sp. (e.g., peanuts, peas, and beans—such as sword beans and broad beans); Chenopodiaceae sp. (e.g., Swiss chard, forage beets, spinach, beetroot); Malvaceae (e.g., okra); Asparagaceae (e.g., asparagus); useful and ornamental plants in horticulture and forestry; and in each case, genetically modified types of these plants.

[0186] As described above, all plants and their parts can be processed according to the present invention. In a preferred embodiment, wild plant species and cultivars, or those obtained through conventional biological breeding methods such as hybridization or protoplast fusion, and their parts are processed. In another preferred embodiment, transgenic plants and cultivars (genetically modified organisms) obtained through genetic engineering methods—if appropriate, in combination with conventional methods—and their parts are processed. The terms “part” or “plant part” or “plant component” have been explained above. Particularly preferred are plants of commercially available conventional cultivars or those currently in use, processed according to the present invention. Cultivars are understood to mean plants with new characteristics (“traits”) grown through conventional breeding, through mutation, or through recombinant DNA technology. They can be cultivars, varieties, biotypes, or genotypes.

[0187] The processing method of this invention can be used to process genetically modified organisms (GMOs), such as plants or seeds. Genetically modified plants (or transgenic plants) are plants in which a heterologous gene has been stably integrated into the genome. The term "heterologous gene" essentially refers to a gene that is provided or assembled outside the plant and, when introduced into the nucleus, chloroplast, or mitochondrial genome, confers new or improved agronomic or other traits to the transformed plant because it expresses a protein or polypeptide of a gene of interest or other gene present in the plant, or downregulates or silences other genes present in the plant (using, for example, antisense techniques, co-suppression techniques, or RNAi-technology [RNA interference]). Heterologous genes located in the genome are also called transgenes. Transgenes defined according to their specific presence in the plant genome are called transformations or transgenic lines.

[0188] Depending on the plant species or cultivar, its location, and growing conditions (soil, climate, growth period, nutrition), the treatments of this invention can also produce additive (“synergistic”) effects. For example, the following effects exceeding actual expectations may occur: reduced application rates and / or broadened activity spectrum and / or increased efficacy of the active ingredients and compositions that can be used according to this invention; better plant growth; increased tolerance to high or low temperatures; increased tolerance to drought or to water or soil salinity; improved flowering performance; easier harvesting; accelerated ripening; increased harvest yield; larger fruits; taller plants; greener leaves; earlier flowering; higher quality and / or higher nutritional value of harvested products; higher sugar concentration in fruits; and better storage stability and / or processability of harvested products.

[0189] Preferably, the plants and plant cultivars treated according to the present invention include all plants (whether obtained by breeding means and / or by biotechnological means) that have genetic material that confers particularly advantageous traits upon these plants.

[0190] Examples of nematode-resistant plants are described in the following U.S. patent applications: for example, 11 / 765,491, 11 / 765,494, 10 / 926,819, 10 / 782,020, 12 / 032,479, 10 / 783,417, 10 / 782,096, 11 / 657,964, 12 / 192,904, 11 / 396,808, 12 / 166,253, 12 / 166,239, 12 / 166,124, 12 / 166,209, 11 / 762,886, 12 / 364,335, 11 / 763,947, 12 / 252,453, 12 / 209,354, 12 / 491,396, and 12 / 497,221.

[0191] The plants that can be treated according to the invention are hybrid plants that have expressed characteristics of heterosis or hybridization effects, which typically result in higher yields, vigor, better health, and resistance to biotic and abiotic stresses. These plants are typically obtained by crossing one self-pollinating male-sterile parent (hybrid female) with another self-pollinating male-fertile parent (hybrid male). Hybrid seeds are typically harvested from male-sterile plants and sold to growers. Male-sterile plants can sometimes (e.g., in maize) be produced by emasculation (i.e., mechanical removal of male reproductive organs or male flowers), but more commonly, male sterility is caused by genetic determinants in the plant genome. In this case, and particularly when the seeds are the desired product harvested from hybrid plants, it is generally advantageous to ensure that male fertility in the hybrid plant (which contains the genetic determinant responsible for male sterility) is fully restored. This can be achieved by ensuring that the hybrid male has a suitable fertility-restoring gene that restores male fertility in the hybrid plant containing the genetic determinant responsible for male sterility. The genetic determinants of male sterility can be located in the cytoplasm. For example, examples of cytoplasmic male sterility (CMS) in Brassica species have been documented. However, the genetic determinants of male sterility can also be located in the nuclear genome. Male-sterile plants can also be obtained through plant biotechnological methods (e.g., genetic engineering). WO89 / 10396 describes a particularly useful method for obtaining male-sterile plants in which, for example, ribonucleases (e.g., Bacillus RNase) are selectively expressed in the tapetal cells of the stamen. Fertility can then be restored by expressing ribonuclease inhibitors (e.g., Bacillus RNase inhibitors) in the tapetal cells.

[0192] The plants or plant cultivars (obtained through plant biotechnology methods such as genetic engineering) that can be treated according to the present invention are herbicide-tolerant plants, i.e., plants tolerant to more than one given herbicide. These plants can be obtained through genetic transformation or by selecting plants containing mutations that confer such herbicide tolerance.

[0193] Herbicide-tolerant plants are, for example, glyphosate-tolerant plants, meaning plants that are tolerant to the herbicide glyphosate or its salts. Plants can be made tolerant to glyphosate in various ways. For example, glyphosate-tolerant plants can be obtained by transforming plants with a gene encoding 5-enolpyruvylshikimate-3-phosphate synthase (EPSPS). Examples of the EPSPS gene include the AroA gene (mutant CT7) of *Salmonella typhimurium* (Comai et al., 1983, Science 221, 370-371), the CP4 gene of *Agrobacterium* sp. (Barry et al., 1992, Curr. Topics Plant Physiol. 7, 139-145), the gene encoding EPSPS in petunia (Shah et al., 1986, Science 233, 478-481), the gene encoding EPSPS in tomato (Gasser et al., 1988, J. Biol. Chem. 263, 4280-4289), or the gene encoding EPSPS in *Eleusine* (WO01 / 66704). The EPSPS gene can also be a mutant EPSPS. Glyphosate-tolerant plants can also be obtained by expressing a gene encoding glyphosate oxidoreductase. Glyphosate-tolerant plants can also be obtained by expressing genes encoding glyphosate acetyltransferases. Glyphosate-tolerant plants can also be obtained by selecting plants containing mutants of the aforementioned naturally occurring genes. Plants expressing the EPSPS gene, which confers glyphosate tolerance, have been documented. Plants expressing other genes that confer glyphosate tolerance (e.g., decarboxylase genes) have also been documented.

[0194] Other herbicide-resistant plants are those resistant to herbicides that inhibit glutamine synthase (e.g., bialaphos, phosphinothricin, or glufosinate). These plants can be obtained by expressing enzymes that detoxify the herbicide or by expressing mutant glutamine synthases resistant to inhibition. An example of such effective detoxification enzymes is an enzyme encoding phosphinothricin acetyltransferase (e.g., the bar or pat protein in Streptomyces species). Plants expressing exogenous phosphinothricin acetyltransferase have been documented.

[0195] Other herbicide-tolerant plants are those resistant to herbicides that inhibit hydroxyphenylpyruvate dioxygenase (HPPD), the enzyme that catalyzes the conversion of p-hydroxyphenylpyruvate (HPP) to hydantoin. Plants resistant to HPPD inhibitors can be transformed using genes encoding naturally occurring resistant HPPD enzymes, or genes encoding mutant or chimeric HPPD enzymes, as described in WO96 / 38567, WO99 / 24585, WO99 / 24586, WO2009 / 144079, WO2002 / 046387, or US6,768,044. Resistance to HPPD inhibitors can also be acquired by transforming plants with genes encoding enzymes that can still form hydantoin despite the inhibition of natural HPPD enzymes by HPPD inhibitors. Such plants are described in WO99 / 34008 and WO02 / 36787. In addition to using genes encoding HPPD tolerance enzymes, plant tolerance to HPPD inhibitors can be improved by transforming plants using genes encoding prephenylate dehydrogenases, as described in WO2004 / 024928. Furthermore, plants can be made more tolerant to HPPD inhibitors by inserting genes encoding enzymes that metabolize or degrade HPPD inhibitors (e.g., CYP450 enzymes) into their genome (see WO2007 / 103567 and WO2008 / 150473).

[0196] Other herbicide-resistant plants are those resistant to acetolactate synthase (ALS) inhibitors. Known ALS inhibitors include, for example, sulfonylureas, imidazolinones, triazolopyrimidines, pyrimidinoxy (thio)benzoates, and / or sulfonylaminocarbonyltriazolinone herbicides. Different mutations in the ALS enzyme (also known as acetylhydroxy acid synthase, AHAS) are known to confer resistance to different herbicides and herbicide groups, as documented, for example, in Tranel and Wright (Weed Science, 2002, 50, 700-712). The preparation of sulfonylurea-resistant and imidazolinone-resistant plants has been documented. Other sulfonylurea-resistant and imidazolinone-resistant plants have also been documented.

[0197] Other plants tolerant to imidazolinones and / or sulfonylureas can be obtained by induced mutations, selection in cell culture media in the presence of herbicides, or by mutation breeding (see, for example, US 5,084,082 on soybeans, WO 97 / 41218 on rice, US 5,773,702 and WO99 / 057965 on sugar beets, US 5,198,599 on lettuce, or WO 01 / 065922 on sunflower).

[0198] Plants or plant cultivars (obtained through plant biotechnology methods such as genetic engineering) treated according to the present invention can also be tolerant to abiotic stresses. Such plants can be obtained through genetic transformation or by selecting plants containing mutations that confer resistance to the stress. Particularly useful stress-tolerant plants include the following:

[0199] a. Plants containing transgenic elements that can reduce the expression and / or activity of the poly(adenosine diphosphate-ribose) polymerase (PARP) gene in plant cells or plants;

[0200] b. Plants containing stress-enhancing transgenes that can reduce the expression and / or activity of PARG-encoding genes in plants or plant cells;

[0201] c. A stress-enhancing transgenic plant containing a plant functional enzyme encoding the nicotinamide adenine dinucleotide salvage biosynthetic pathway, wherein the plant functional enzyme includes nicotinamide enzyme, nicotinyl phosphoribosyltransferase, nicotinic acid mononucleotide adenylate transferase, nicotinamide adenine dinucleotide synthase, or nicotinamide phosphoribosyltransferase.

[0202] The plants or plant cultivars treated according to the present invention (obtained through plant biotechnology methods such as genetic engineering) may also exhibit altered quantities, quality, and / or storage stability of the harvested products, and / or altered characteristics of specific components of the harvested products, said plants or plant cultivars being, for example:

[0203] 1) Transgenic plants with synthetic modified starch have altered physicochemical properties compared to synthetic starch in wild-type plant cells or plants. In particular, the content of amylose or the ratio of amylose to amylopectin, degree of branching, average chain length, side chain distribution, viscous behavior, gel strength, starch granule size and / or starch granule morphology have been altered to make them more suitable for specific applications.

[0204] 2) Transgenic plants that synthesize non-starch carbohydrate polymers, or transgenic plants that synthesize non-starch carbohydrate polymers with altered properties compared to unmodified wild-type plants. Examples include plants that produce polyfructose (especially inulin and fructan types); plants that produce α-1,4-glucan; plants that produce α-1,6-branched α-1,4-glucan; and plants that produce alternans.

[0205] 3) Genetically modified plants that produce hyaluronic acid.

[0206] 4) Genetically modified or hybrid plants with specific characteristics such as “high soluble solids content”, “low irritation” (LP) and / or “long shelf life” (LS), such as onions.

[0207] The plants or plant cultivars (obtained through plant biotechnology methods such as genetic engineering) processed according to the present invention are plants with altered fiber properties, such as cotton plants. These plants can be obtained through genetic transformation or by selecting plants containing mutations that confer the altered fiber properties, said plants including:

[0208] a) Plants containing genes for cellulose synthase in modified forms, such as cotton plants;

[0209] b) Plants containing altered forms of rsw2 or rsw3 homologous nucleic acids, such as cotton plants, like cotton plants with enhanced sucrose phosphate synthase expression;

[0210] c) Plants with enhanced expression of sucrose synthase, such as cotton plants;

[0211] d) Plants that alter the timing of plasmodesmata gating at the base of fiber cells, such as cotton plants, by, for example, downregulating fiber-selective β-1,3-glucanase;

[0212] e) Plants with reactivity-altering fibers—for example, through the expression of N-acetylglucosamine transferase genes (including nodC) and chitin synthase genes, such as cotton plants.

[0213] The plants or plant cultivars (obtained through plant biotechnology methods such as genetic engineering) processed according to the present invention are plants with altered oil spectrum characteristics, such as rapeseed or related Brassica plants. Such plants can be obtained through genetic transformation or by selecting plants containing mutations that confer said altered oil characteristics, including:

[0214] a) Plants that produce oils with high oleic acid content, such as rapeseed.

[0215] b) Plants that produce oils with low linolenic acid content, such as rapeseed.

[0216] c) Plants that produce oils with low levels of saturated fatty acids, such as rapeseed.

[0217] The plants or plant cultivars treated according to the present invention (which can be obtained through plant biotechnology methods such as genetic engineering) can also be virus-resistant (e.g., resistant to potato virus Y) plants (from Argentine Tecnoplant SY230 and SY233 strains), such as potatoes, or plants resistant to diseases such as potato late blight (e.g., RB gene), or plants exhibiting reduced cold-induced sweetness (carrying the genes Nt-Inh, II-INV) or plants exhibiting a dwarf phenotype (A-20 oxidase gene).

[0218] The plants or plant cultivars (obtained through plant biotechnology methods such as genetic engineering) treated according to the present invention can also be plants with altered shattering characteristics, such as rapeseed or related Brassica species. Such plants can be obtained through genetic transformation or by selecting plants containing mutations that confer said altered characteristics, and include plants with reduced or mitigated shattering characteristics, such as rapeseed.

[0219] Particularly useful transgenic plants that can be treated according to the present invention are plants having a transformed line or a combination of transformed lines, said plants being the subject of a request for a non-regulated status that has been approved or is pending approval by the Animal and Plant Health Inspection Service (APHIS) of the United States Department of Agriculture (USDA). Information on this is available at any time from APHIS (4700 River Road, Riverdale, MD 20737, USA), for example via the website http: / / www.aphis.usda.gov / brs / not_reg.html.

[0220] Particularly useful transgenic plants that can be processed according to the present invention are plants containing transformant lines or combinations of transformant lines, and which are listed in, for example, databases of regulatory agencies in different countries or regions (see, for example, http: / / gmoinfo.jrc.it / gmp_browse.aspx and http: / / cera-gmc.org / index.php?evidcode=&hstIDXCode=&gType=&AbbrCode=&atCode=&stCode=&coIDCode=&action=gm_crop_database&mode=Submit).

[0221] When the active substances of this invention are used on genetically modified crops, in addition to the inhibitory effect on harmful plants observed in other crops, they often exhibit specific effects on the corresponding genetically modified crops. For example, they can improve or expand the range of weed control, improve the application rate, preferably combine the herbicide resistance of the genetically modified crop with the performance of the herbicide, and affect the growth and yield of the genetically modified crop. Therefore, this invention also provides the use of the compounds as herbicides to control harmful plants in genetically modified crop plants.

[0222] Furthermore, the compounds of this invention can significantly regulate crop growth. By modulating plant metabolism, these compounds can be used to directionally control plant components and promote harvesting, for example, by causing plant drying and dwarfing. They are also suitable for regulating and inhibiting unwanted plant growth without disrupting crop growth. Inhibiting plant growth plays a crucial role in many monocot and dicot crops because it can reduce or completely prevent lodging.

[0223] In this invention, if there is a conflict between the naming of compounds and their structural formulas, the structural formula shall prevail, unless the structural formula is obviously incorrect.

[0224] The compound of formula (I) provided by this invention has better herbicidal activity and safety compared with the prior art. Detailed Implementation

[0225] The following examples are for illustrative purposes only and should not be construed as limiting the invention in any way. The scope of protection of this invention is defined by the claims. Simple substitutions or modifications made to this invention by those skilled in the art are all within the scope of the technical solutions protected by this invention.

[0226] Several methods for preparing the compounds of the present invention are described in detail in the following schemes and examples. The raw materials can be commercially available or prepared by methods known in the literature or as detailed in the description. Those skilled in the art will understand that other synthetic routes can also be used to synthesize the compounds of the present invention. Although specific raw materials and conditions in the synthetic routes have been described below, they can be easily replaced with other similar raw materials and conditions. Such variations or modifications to the preparation methods of the present invention, such as various isomers of the compounds, are all included within the scope of the present invention. Furthermore, the preparation methods described below can be further modified according to the disclosure of the present invention using conventional chemical methods well known to those skilled in the art. For example, protecting appropriate groups during the reaction process, etc.

[0227] The following method examples are provided to further illustrate the preparation methods of the present invention. The specific substances, types, and conditions used are intended to further explain the invention and are not intended to limit its reasonable scope. The reagents used in the synthetic compounds described below are either commercially available or can be easily prepared by those skilled in the art.

[0228] The analytical instruments described in the examples are as follows:

[0229] I. High Performance Liquid Chromatography (hereinafter referred to as HPLC): Using an Agilent Technologies 1260 Infinity II instrument.

[0230] Pillar: Agilent Eclipse Plus C18 3.5μm, 4.6*100mm

[0231] Mobile phase: A: Water + 0.1% phosphoric acid; B: Acetonitrile; Temperature: 30℃

[0232] Gradient: 10%B to 95%B over 15 min; 95%B over 3 min

[0233] Flow rate: 1 mL / min

[0234] II. Ultra-high performance liquid chromatography-tandem mass spectrometry (hereinafter referred to as LC-MS): Waters, ACQUITY H-Class UPLC-SQ Detector2 instrument.

[0235] Column: ACQUITY BEH C18 1.7μm,2.1*50mm Column

[0236] Mobile phase: A: Water + 0.2% formic acid; B: Acetonitrile; Temperature: 30℃

[0237] Gradient: 10%B to 95%B over 5 minutes; 95%B over 1 minute

[0238] Flow rate: 0.5 mL / min

[0239] MS method: ESI positive, negative, quality range (m / z): 100-800

[0240] III. Gas Chromatography-Tandem Mass Spectrometry (hereinafter referred to as GC-MS): Using Agilent Technologies, 7890B GC System-5977A MSD equipment.

[0241] Column: Agilent Technologies, HP-5MS UI 0.25μm, 30m*0.250mm

[0242] Injector temperature: 250℃

[0243] Column flow rate: Helium 1 mL / min

[0244] Method: Hold at 40℃ for 2 min, increase temperature to 280℃ at 20℃ / min, hold at 280℃ for 5 min, total time 19 min.

[0245] MSD transmission line temperature: 280℃

[0246] EI ion source temperature: 230℃, MS quadrupole temperature: 150℃, scan range: 30.00-400.00

[0247] IV. Automatic polarimeter: Using Rudolph Research Analytical... II Automatic Polarimeter Equipment

[0248] Wavelength: 589nm

[0249] Path length: 50.00mm

[0250] Temperature: 20℃

[0251] The concentration of the compound being tested, “c” (in g / 100 mL), and the solvent used.

[0252] In addition, the proton nuclear magnetic resonance spectra described below (hereinafter referred to as...) 1 The chemical shift values ​​of H-NMR were measured at 400 MHz (Bruker, AVANCE III HD 400M) in deuterated chloroform (CDCl3) using Me4Si (tetramethylsilane) as the reference material. When measured in deuterated dimethyl sulfoxide, the chemical shift values ​​are shown as "(DMSO-d6)" in the data. It should be noted that... 1 The symbols in the chemical shift values ​​of H-NMR have the following meanings:

[0253] s: singlet, d: doublet, dd: doublett, dt: doublettuplet, td: triplettuplet, ddd: doublettuplet, t: triplet, q: quartet, sep: septet, m: multiplet, brs: broad singlet. Furthermore, in cases where two or more stereoisomers are present, the chemical shift values ​​for the resolvable signal are marked with "and".

[0254] Examples of representative compounds are given below. The synthesis methods of other compounds are similar and will not be described in detail here.

[0255] The following embodiments illustrate the present invention in detail.

[0256] Example 1

[0257] Preparation of intermediate II-1

[0258] Step 1: Preparation of intermediate II-1.1:

[0259] At room temperature, hydroxylamine hydrochloride (58.7 g, 0.84 mol), ethanol (300 mL), and sodium acetate (69 g, 0.84 mol) were added to a 1000 mL single-necked flask and stirred until homogeneous. Then, 3,5-difluorobenzaldehyde (100 g, 0.7 mol) was added dropwise, and the reaction was allowed to proceed for 3 hours. After the reaction was complete, the solvent was removed under reduced pressure, and the mixture was extracted twice with 100 mL of dichloromethane. The combined organic phases were washed once with saturated brine. The mixture was dried over anhydrous sodium sulfate, and the solvent was removed under reduced pressure to give intermediate II-1.1 (white solid, 108 g).

[0260] Step 2: Preparation of intermediate II-1.2:

[0261] At room temperature, intermediate II-1.1 (5 g, 31.8 mmol) and N,N-dimethylformamide (10 mL) were added to a 50 mL single-necked flask and stirred in an ice bath. N-chlorosuccinimide (5.15 g, 38.57 mmol) was added, and the reaction was continued in an ice bath for 3 hours. After the reaction was complete, the system was extracted twice with 30 mL of dichloromethane, and the combined organic phases were washed once with saturated brine. The mixture was dried over anhydrous sodium sulfate, and the solvent was removed by vacuum distillation to give intermediate II-1.2 (white solid, 5 g).

[0262] Step 3: Preparation of intermediate II-1.3:

[0263] At room temperature, 110.125 g (1 mol) of 40% acetaldehyde aqueous solution and 70 mL of 1,4-dioxane were added to a 1000 mL single-necked flask and stirred. Methyl acrylate (258 g, 3 mol) and triethylenediamine (112.17 g, 1 mol) were added, and the reaction was allowed to proceed for 3 hours. After the reaction was complete, the solvent was removed by vacuum distillation, followed by extraction twice with 200 mL of dichloromethane. The combined organic phases were washed once with saturated brine. The mixture was dried over anhydrous sodium sulfate, and the solvent was removed by vacuum distillation to give intermediate II-1.3 (yellow liquid, 85 g).

[0264] Step 4: Preparation of intermediate II-1.4:

[0265] At room temperature, intermediate II-1.2 (2 g, 10.44 mmol) and isopropanol (20 mL) were added to a 50 mL single-necked flask and stirred to dissolve. Then, intermediate II-1.3 (1.36 g, 10.44 mmol) and sodium bicarbonate (4.4 g, 52.2 mmol) were added, and the mixture was heated to 50 °C and reacted for 2 hours. After the reaction was complete, the reaction solution was filtered, and the filtrate was extracted twice with 30 mL of dichloromethane. The combined organic phases were washed once with saturated brine. The solution was dried over anhydrous sodium sulfate, the solvent was removed under reduced pressure, and the intermediate II-1.4 (white solid, 2.6 g) was purified by column chromatography (eluent: petroleum ether: ethyl acetate = 5:1).

[0266] Step 5: Preparation of intermediate II-1.5:

[0267] At room temperature, intermediate II-1.4 (2.6 g, 9.1 mmol) and dichloromethane (10 mL) were added to a 50 mL single-necked flask and placed in an ice bath. Then, pyridine (1.46 mL, 18.2 mmol) was added, followed by dropwise addition of trifluoromethanesulfonic anhydride (2.30 mL, 13.67 mmol). The reaction was carried out at room temperature for 2 hours. After the reaction was complete, the system was extracted twice with 30 mL of dichloromethane. The combined organic phases were washed once with saturated brine. The mixture was dried over anhydrous sodium sulfate, and the solvent was removed under reduced pressure to obtain crude intermediate II-1.5 (yellow solid, 3.2 g). This was then directly added to the next step without further treatment.

[0268] Step 6: Preparation of intermediate II-1.6:

[0269] At room temperature, intermediate II-1.5 (3.2 g, 7.67 mmol) and N,N-dimethylacetamide (20 mL) were added to a 50 mL single-necked flask and stirred to dissolve. 1,8-diazabicyclo[5.4.0]undec-7-ene (1.375 mL, 9.204 mmol) was added dropwise, and the mixture was stirred overnight at room temperature. After the reaction was complete, the mixture was extracted twice with 30 mL of ethyl acetate. The combined organic phases were washed once with saturated brine. The mixture was dried over anhydrous sodium sulfate, the solvent was removed under reduced pressure, and the intermediate II-1.6 (white solid, 1.39 g) was purified by column chromatography (eluent: petroleum ether: ethyl acetate = 5:1). 1H NMR (400MHz, CDCl3) δ7.18 (dd, J=8.0, 2.3Hz, 2H), 6.87 (tt, J=8.7, 2.3Hz, 1H), 6.13 (dd, J=17.2, 10.7Hz, 1H) ,5.55(d,J=17.2Hz,1H),5.38(d,J=10.7Hz,1H),3.93(d,J=17.0Hz,1H),3.83(s,3H),3.34(d,J=17.0Hz,1H).

[0270] Step 7: Preparation of Intermediate II-1:

[0271] At room temperature, intermediate II-1.6 (6 g, 22.4 mmol) and tetrahydrofuran (30 mL) were added to a 100 mL single-necked flask, stirred to dissolve, and then 20% sodium hydroxide aqueous solution (6.72 g, 33.6 mmol) was added. The mixture was refluxed for 5 hours. After the reaction was completed, the reaction solution was cooled to room temperature, and the pH was adjusted to 1-2 with dilute hydrochloric acid (10%). A solid precipitated out, which was filtered and dried to obtain intermediate II-1 (white solid, 5 g). 1 H NMR(400MHz, CDCl3)δ8.88(s,1H),7.22–7.13(m,2H),6.97–6.84(m,1H),6.16(dd,J=17.2,10.7Hz, 1H), 5.63 (d, J = 17.2Hz, 1H), 5.44 (d, J = 10.7Hz, 1H), 3.92 (d, J = 17.1Hz, 1H), 3.40 (d, J = 17.1Hz, 1H).

[0272] Example 2

[0273] Preparation of intermediate II-19

[0274] Step 1: Preparation of Intermediate II-19.1

[0275] At room temperature, 3-chloro-4,5-difluorobenzoic acid (5 g, 25.97 mmol) and dichloromethane (50 mL) were added to a 250 mL single-necked flask, followed by 2 drops of N,N-dimethylformamide (DMF), and then oxaloyl chloride (3.3 mL, 38.95 mmol). A vigorous release of gas was observed. The mixture was stirred at room temperature for 2 hours, and then the solvent and excess oxaloyl chloride were evaporated under reduced pressure. The resulting crude intermediate II-19.1 was used for the next step without further purification.

[0276] Step 2: Preparation of Intermediate II-19.2

[0277] At room temperature, methoxymethylamine (2.38 g, 38.95 mmol), triethylamine (3.94 g, 38.95 mmol), and 10 mL of dichloromethane were added to a 100 mL single-necked flask. The mixture was cooled to 0 °C and stirred. The crude intermediate II-19.1 prepared in the previous step was completely dissolved in 20 mL of dichloromethane and added dropwise to the reaction solution. The mixture was then heated to room temperature and stirred for 2 h. After the reaction was complete, water was added. The mixture was stirred for 10 min, allowed to stand for phase separation, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was purified by reverse-phase column chromatography to give intermediate II-19.2 (white solid, 5 g).

[0278] Step 3: Preparation of Intermediate II-19.3

[0279] At room temperature, intermediate II-19.2 (5 g, 21.3 mmol) and tetrahydrofuran (20 mL) were added to a 100 mL reaction flask. The mixture was cooled to -20 °C, and diisobutylaluminum hydride toluene solution (1.5 M) (21.3 mL, 31.95 mmol) was added dropwise. The reaction was stopped after 2 h. After the reaction was completed, saturated aqueous solution of potassium sodium tartrate was added, and the mixture was extracted with ethyl acetate and purified by column chromatography to obtain intermediate II-19.3 (yellow liquid, 1.26 g). 1 H NMR (400MHz, DMSO) δ9.94 (s, 1H), 8.06 (dt, J = 6.2, 1.7Hz, 1H), 8.03-7.95 (m, 1H).

[0280] Step 4: Preparation of Intermediate II-19.4

[0281] At room temperature, hydroxylamine hydrochloride (595 mg, 8.56 mmol), ethanol (10 mL), and sodium acetate (702 mg, 8.56 mmol) were added to a 50 mL single-necked flask and stirred until homogeneous. Intermediate II-19.3 (1.26 g, 7.14 mmol) was then added dropwise, and the reaction was allowed to proceed for 3 hours. After the reaction was complete, the solvent was removed under reduced pressure, and the mixture was extracted twice with dichloromethane. The combined organic phases were washed once with saturated brine. The mixture was dried over anhydrous sodium sulfate, and the solvent was removed under reduced pressure to obtain intermediate II-19.4 (white solid, 1.25 g).

[0282] Step 5: Preparation of Intermediate II-19.5

[0283] At room temperature, intermediate II-19.4 (1.25 g, 6.52 mmol) and N,N-dimethylformamide (20 mL) were added to a 50 mL single-necked flask and stirred in an ice bath. N-chlorosuccinimide (1.04 g, 7.83 mmol) was added, and the reaction was continued in an ice bath for 3 hours. After the reaction was complete, the reaction solution was extracted twice with 30 mL of dichloromethane. The combined organic phases were washed once with saturated brine. The solution was dried over anhydrous sodium sulfate, and the solvent was removed by vacuum distillation to give intermediate II-19.5 (yellow oil, 1.5 g).

[0284] Step 6: Preparation of Intermediate II-19.6

[0285] At room temperature, intermediate II-19.5 (700 mg, 3.1 mmol) and isopropanol (10 mL) were added to a 50 mL single-necked flask and stirred to dissolve. Then, methyl 3-hydroxy-2-methylenebutyrate (403 mg, 3.1 mmol) and sodium bicarbonate (1.3 g, 15.5 mmol) were added, and the mixture was heated to 50 °C and reacted for 2 hours. After the reaction was complete, the reaction solution was filtered, and the filtrate was extracted twice with 30 mL of dichloromethane. The combined organic phases were washed once with saturated brine. The solution was dried over anhydrous sodium sulfate, the solvent was removed under reduced pressure, and the intermediate II-19.6 (yellow solid, 880 mg) was purified by column chromatography (eluent: petroleum ether: ethyl acetate = 5:1).

[0286] Step 7: Preparation of Intermediate II-19.7

[0287] At room temperature, intermediate II-19.6 (880 mg, 2.75 mmol) and dichloromethane (20 mL) were added to a 50 mL single-necked flask and placed in an ice bath. Then, pyridine (445 μL, 5.5 mmol) was added, followed by dropwise addition of trifluoromethanesulfonic anhydride (695 μL, 4.13 mmol), and the reaction was carried out at room temperature for 2 hours. After the reaction was complete, the reaction mixture was extracted twice with 30 mL of dichloromethane. The combined organic phases were washed once with saturated brine. The mixture was dried over anhydrous sodium sulfate, and the solvent was removed under reduced pressure to obtain crude intermediate II-19.7 (yellow oil, 1.27 g). This was then directly added to the next step without further treatment.

[0288] Step 8: Preparation of Intermediate II-19.8

[0289] At room temperature, intermediate II-19.7 (1.20 g, 2.66 mmol) and N,N-dimethylformamide (15 mL) were added to a 50 mL single-necked flask and stirred to dissolve. 1,8-diazabicyclo[5.4.0]undec-7-ene (476 μL, 3.19 mmol) was added dropwise, and the mixture was stirred overnight at room temperature. After the reaction was complete, the mixture was extracted twice with 30 mL of ethyl acetate. The combined organic phases were washed once with saturated brine. The mixture was dried over anhydrous sodium sulfate, the solvent was removed under reduced pressure, and the intermediate II-19.8 (oily solid, 497 mg) was purified by column chromatography (eluent: petroleum ether: ethyl acetate = 5:1). 1 H NMR (400MHz, DMSO) δ7.89-7.68 (m, 2H), 6.15 (dd, J = 17.3, 10.7Hz, 1H), 5.41 (dd, J =29.0,14.0Hz,2H),3.96(d,J=17.8Hz,1H),3.75(s,3H),3.69(d,J=17.8Hz,1H).

[0290] Step 9: Preparation of Intermediate II-19

[0291] At room temperature, intermediate II-19.8 (497 mg, 1.65 mmol) and tetrahydrofuran (10 mL) were added to a 100 mL single-necked flask, stirred to dissolve, and then 20% sodium hydroxide aqueous solution (330 mg, 1.65 mmol) was added. The mixture was reacted at room temperature for 1 hour. After the reaction was completed, the pH of the reaction solution was adjusted to 1-2 with dilute hydrochloric acid (10%), and a solid precipitated out. The solid was filtered and dried to obtain intermediate II-19 (white solid, 400 mg). 1 H NMR (400MHz, DMSO) δ13.57 (s, 1H), 7.93-7.67 (m, 2H), 6.15 (dd, J = 17.3, 10.7Hz, 1H), 5.44 (dd ,J=17.3,0.5Hz,1H),5.34(d,J=10.7Hz,1H),3.90(d,J=17.7Hz,1H),3.62(d,J=17.7Hz,1H).

[0292] Example 3

[0293] Preparation of Intermediate II-20

[0294] Step 1: Preparation of intermediate II-20.1:

[0295] At room temperature, intermediate II-19.5 (3 g, 15.7 mmol) and isopropanol (20 mL) were added to a 50 mL reaction flask. Then, methyl methacrylate (1.84 mL, 17.2 mmol) and sodium bicarbonate (6.6 g, 78.5 mmol) were added, and the mixture was heated to 50 °C and reacted for 3 h. After the reaction was complete, the mixture was purified by column chromatography to obtain intermediate II-20.1 (white solid, 4 g). 1 H NMR (400MHz, DMSO) δ7.60-7.45(m,3H),4.27(d,J=15.6Hz,1H),3.94(d,J=15.6Hz,1H),3.73(s,3H),1.64(s,3H).

[0296] Step 2: Preparation of Intermediate II-20:

[0297] At room temperature, intermediate II-20.1 (4 g, 15.67 mmol) and tetrahydrofuran (20 mL) were added to a 100 mL single-necked flask, stirred to dissolve, and then 20% sodium hydroxide aqueous solution (3.76 g, 18.8 mmol) was added. The mixture was reacted at room temperature for 1 hour. After the reaction was completed, the pH of the reaction solution was adjusted to 1-2 with dilute hydrochloric acid (10%), and a solid precipitated out. The solid was filtered and dried to obtain intermediate II-20 (white solid, 3.6 g). 1 H NMR (400MHz, DMSO) δ13.31(s,1H),7.40(d,J=7.3Hz,3H),3.82(d,J=17.6Hz,1H),3.40(d,J=17.5Hz,1H),1.58(s,3H).

[0298] Example 4

[0299] Preparation of intermediate II-28

[0300] Step 1: Preparation of intermediate II-28.1:

[0301] Similar to the preparation procedure of intermediate II-1.1, intermediate II-28.1 was prepared by reacting 3,5-dimethoxybenzaldehyde with hydroxylamine hydrochloride.

[0302] Step 2: Preparation of intermediate II-28.2:

[0303] At room temperature, intermediate II-28.1 (1 g, 5.5 mmol) and dichloromethane (5 mL) were added to a 25 mL single-necked flask, followed by triethylamine (1.68 g, 13.2 mmol). The reaction mixture was stirred in an ice bath for 10 minutes, and then sodium hypochlorite solution (10% available chlorine) (5.5 mL, 7.4 mmol) was slowly added. The mixture was stirred at 0 °C for 1 hour, and then methyl methacrylate (553 mg, 5.52 mmol) was added. The mixture was stirred at 0 °C for 1 hour, and then the solvent was removed under reduced pressure. Water was added, and the mixture was extracted twice with ethyl acetate. The organic phases were combined, and the solvent was removed under reduced pressure to give intermediate II-28.2 (white solid, 970 mg).

[0304] Step 3: Preparation of intermediate II-28:

[0305] At room temperature, intermediate II-28.2 (970 mg, 3.47 mmol) and tetrahydrofuran (20 mL) were added to a 100 mL single-necked flask, stirred to dissolve, and then 20% sodium hydroxide aqueous solution (800 mg, 4 mmol) was added. The reaction was carried out at room temperature for 1 hour. After the reaction was completed, the pH of the reaction solution was adjusted to 1-2 with dilute hydrochloric acid (10%), and a solid precipitated out. The solid was filtered and dried to obtain intermediate II-28 (white solid, 850 mg). 1 H NMR (400MHz, DMSO) δ13.11(s,1H),6.80(d,J=2.2Hz,2H),6.59(t,J=2.1Hz,1H),3.77(s,6H),3.38(d,2H),1.55(s,3H).

[0306] Example 5

[0307] Preparation of intermediate II-35

[0308] Step 1: Preparation of intermediate II-35.1:

[0309] At 0 °C, 3-chloro-5-hydroxybenzonitrile (3 g, 19 mmol), difluorobromomethyltrimethylsilane (7.8 g, 38 mmol), and dichloromethane (30 mL) were added to a 250 mL single-necked flask. After stirring for 20 minutes, 20% potassium hydroxide aqueous solution (27 mL, 114 mmol) was added dropwise, and the reaction was allowed to proceed for 1.5 hours. After the reaction was complete, the mixture was extracted twice with 30 mL of dichloromethane. The combined organic phases were washed once with saturated brine, dried over anhydrous sodium sulfate, and the solvent was removed under reduced pressure. After purification by column chromatography, intermediate II-35.1 (pale yellow oil, 2.89 g) was obtained.

[0310] Step 2: Preparation of intermediate II-35.2:

[0311] At room temperature, intermediate II-35.2 (2.89 g, 14.2 mmol), sodium hypophosphite (2.5 g, 28.4 mmol), pyridine (8 mL), acetic acid (2 mL), water (2 mL), and Raney Ni (water-moist, 0.2 g) were added to a 250 mL single-necked flask. The reaction system was refluxed under a nitrogen atmosphere for 10 hours. After the reaction was completed, the system was cooled to room temperature, diluted with 20 mL of ethyl acetate, and the solid suspension was filtered off. The solvent was removed under vacuum, and the system was purified by column chromatography (petroleum ether:ethyl acetate = 3:1) to obtain II-35.2 (yellow oil, 2.4 g).

[0312] Step 3: Preparation of intermediate II-35.3:

[0313] Similar to the preparation procedure of intermediate II-1.1, intermediate II-35.3 was prepared by reacting 3-chloro-5-(difluoromethoxy)benzaldehyde with hydroxylamine hydrochloride.

[0314] Step 4: Preparation of intermediate II-35.4:

[0315] Similar to the preparation procedure of intermediate II-1.2, intermediate II-35.4 was prepared by reacting II-35.3 with N-chlorosuccinimide.

[0316] Step 5: Preparation of intermediate II-35.5:

[0317] Similar to the preparation procedure of intermediate II-20.1, intermediate II-35.5 was prepared by reacting II-35.4 with methyl methacrylate.

[0318] Step 6: Preparation of Intermediate II-35:

[0319] At room temperature, intermediate II-35.5 (1.52 g, 4.76 mmol), tetrahydrofuran (5 mL), and water (20 mL) were added to a 100 mL single-necked flask and stirred until homogeneous. Lithium hydroxide monohydrate (220 mg, 5.2 mmol) was then added to the system, and the reaction was allowed to proceed for 30 minutes. After the reaction was complete, 1 M hydrochloric acid was added dropwise to adjust the pH to 3–4. The mixture was then extracted with 20 mL of ethyl acetate. The combined organic phases were washed once with saturated brine, dried over anhydrous sodium sulfate, and the solvent was removed by vacuum evaporation to obtain II-35 (a pale yellow solid, 1.41 g). 1H NMR (400MHz, DMSO) δ13.26(s,1H),7.56-7.40(m,3H),7.32(ddt,J=9.5,4.7,2.8Hz,1H),3.81(d,J=17.4Hz,1H),3.40(d,J=17.4Hz,1H),1.58(s,3H).

[0320] Example 6

[0321] Preparation of intermediate II-39

[0322] Step 1: Preparation of intermediate II-39.1:

[0323] At room temperature, intermediate II-19.5 (2.44 g, 12.7 mmol) and isopropanol (10 mL) were added to a 50 mL reaction flask. Methyl methoxyacrylate (1.47 mg, 12.7 mmol) and sodium bicarbonate (5.3 g, 63.5 mmol) were then added, and the mixture was heated to 50 °C and reacted for 3 h. After the reaction was complete, the mixture was purified by column chromatography to obtain intermediate II-39.1 (white solid, 3 g). 1 H NMR (400MHz, DMSO) δ7.47–7.40(m,3H),3.93(d,J=18.8Hz,1H),3.80(s,3H),3.74(d,J=18.8Hz,1H),3.30(s,3H).

[0324] Step 2: Preparation of intermediate II-39:

[0325] At room temperature, intermediate II-39.1 (3 g, 11.06 mmol) and tetrahydrofuran (10 mL) were added to a 50 mL single-necked flask and stirred to dissolve. Lithium hydroxide monohydrate (464 mg, 11.06 mmol) was then added, and the mixture was reacted at room temperature for 1 hour. After the reaction was complete, the pH of the reaction solution was adjusted to 1–2 with dilute hydrochloric acid (10%). A solid precipitated out. The precipitate was filtered and dried to obtain intermediate II-39 (white solid, 2 g). 1 H NMR (400MHz, DMSO) δ13.86 (s, 1H), 7.51-7.38 (m, 3H), 3.87 (d, J = 18.7Hz, 1H), 3.67 (d, J = 18.7Hz, 1H), 3.31 (s, 3H).

[0326] Example 7

[0327] Preparation of intermediate II-69

[0328] Step 1: Preparation of intermediate II-69.1:

[0329] Add 20 g (77.09 mmol) of 1-bromo-3-chloro-5-(trifluoromethyl)toluene and 80 mL of tetrahydrofuran to a 500 mL three-necked flask. Add a 2 mol / L solution of isopropyl magnesium chloride in tetrahydrofuran (115.6 mL, 231.27 mmol) under ice bath conditions. Stir at room temperature for 1 hour until the reaction solution turns pink. Add 16.9 g (231.27 mmol) of N,N-dimethylformamide under ice bath conditions. Stir overnight at room temperature. After the reaction is complete, add excess dilute hydrochloric acid (10%). Filter to remove insoluble matter. Remove the solvent from the filtrate under reduced pressure. Extract twice with 1000 mL of dichloromethane. Combine the organic phases and wash once with saturated brine. Dry over anhydrous sodium sulfate and evaporate the solvent under reduced pressure to give intermediate II-69.1 (yellowish-white solid, 12 g). 1 H NMR (400MHz, CDCl3) δ9.94(s,1H),7.98-7.91(m,2H),7.78-7.73(m,1H).

[0330] Step 2: Preparation of intermediate II-69.2:

[0331] Similar to the preparation procedure of intermediate II-1.1, intermediate II-69.2 was prepared by reacting 3-chloro-5-(trifluoromethyl)benzaldehyde with hydroxylamine hydrochloride. 1 H NMR (400MHz, DMSO) δ11.76(s,1H),8.25(s,1H),7.95-7.82(m,3H).

[0332] Step 3: Preparation of intermediate II-69.3:

[0333] Similar to the preparation procedure of intermediate II-1.2, intermediate II-69.2 was reacted with N-chlorosuccinimide to prepare intermediate II-69.3. 1 HNMR(400MHz,DMSO)δ12.94(s,1H),8.07-7.92(m,3H).

[0334] Step 4: Preparation of intermediate II-69:

[0335] At room temperature, intermediate II-69.3 (5 g, 19 mmol) and isopropanol (20 mL) were added to a 50 mL single-necked flask and stirred to dissolve. Then, 2-(trifluoromethyl)acrylic acid (2.67 g, 19 mmol) and sodium bicarbonate (3.66 g, 97.5 mmol) were added, and the mixture was heated to 50 °C and reacted for 2 hours. After the reaction was complete, the insoluble matter was removed by filtration, and the mixture was extracted twice with 30 mL of dichloromethane. The combined organic phases were washed once with saturated brine. The mixture was dried over anhydrous sodium sulfate, the solvent was removed under reduced pressure, and the intermediate II-69 (white solid, 5.1 g) was purified by column chromatography. 1 H NMR (400MHz, DMSO) δ8.12(s,1H),8.06(s,1H),8.03(s,1H),4.38–4.20(m,2H).

[0336] Example 8

[0337] Preparation of intermediate II-77

[0338] Step 1: Preparation of intermediate II-77.1:

[0339] At room temperature, intermediate II-19.5 (1 g, 5.2 mmol) and isopropanol (20 mL) were added to a 50 mL reaction flask. Then, methyl 2-(chloromethyl)acrylate (0.7 g, 5.3 mmol) and sodium bicarbonate (2.2 g, 26.2 mmol) were added, and the mixture was heated to 50 °C and reacted for 3 h. After the reaction was complete, the mixture was purified by column chromatography to obtain intermediate II-77.1 (white solid, 1.4 g).

[0340] Step 2: Preparation of intermediate II-77:

[0341] At room temperature, intermediate II-77.1 (1.4 g, 5.13 mmol) and tetrahydrofuran (20 mL) were added to a 100 mL single-necked flask and stirred to dissolve. A 20% aqueous solution of lithium hydroxide monohydrate (0.26 g, 6.15 mmol) was then added, and the mixture was reacted at room temperature for 1 hour. After the reaction was complete, the pH of the system was adjusted to 1–2 with dilute hydrochloric acid (10%). The organic phase was extracted with ethyl acetate, dried over anhydrous sodium sulfate, and the solvent was removed under reduced pressure to obtain intermediate II-77 (white solid, 1.3 g). 1 H NMR (400MHz, DMSO) δ7.52-7.36 (m, 3H), 4.11-4.01 (m, 2H), 3.90 (d, J = 18.0Hz, 1H), 3.62 (d, J = 18.0Hz, 1H).

[0342] Example 9

[0343] Preparation of intermediate II-110

[0344] Step 1: Preparation of intermediate II-110.1:

[0345] At room temperature, 3-bromo-5-fluorophenol (5 g, 26.18 mmol) was dissolved in isopropanol (15 mL), and 20% sodium hydroxide aqueous solution (7.8 g, 39.27 mmol) was added at room temperature. After stirring for 30 minutes, dichlorofluoromethane (CHClF2) gas was introduced to replace the solution, and the reaction was carried out at 30 °C for 12 hours. After the reaction was completed, the liquid was separated, and the upper isopropanol phase was taken. The isopropanol was removed by vacuum distillation, and 20 mL of water was added. The mixture was placed in a Dean-Stark apparatus and heated to 100 °C under reflux. The lower liquid in the Dean-Stark apparatus was collected to obtain intermediate II-110.1 (colorless oil, 4.1 g).

[0346] Step 2: Preparation of intermediate II-110.2:

[0347] Intermediate II-110.1 (1 g, 4.15 mmol) was dissolved in tetrahydrofuran (2 mL) under ice bath conditions. A tetrahydrofuran solution of isopropyl magnesium chloride (2 M) (6.22 mL, 12.45 mmol) was added at 0 °C. After reacting at 0 °C for 1.5 h, N,N-dimethylformamide (0.9 g, 12.45 mmol) was added, and the reaction was carried out at room temperature for 1 h. After the reaction was completed, cold saturated ammonium chloride solution was added to quench the reaction. The aqueous phase was extracted three times with ethyl acetate, and then purified by column chromatography to obtain intermediate II-110.2 (yellow oil, 0.56 g).

[0348] Step 3: Preparation of intermediate II-110.3:

[0349] Similar to the preparation procedure of intermediate II-1.1, intermediate II-110.3 was prepared by reacting intermediate II-110.2 with hydroxylamine hydrochloride.

[0350] Step 4: Preparation of intermediate II-110.4:

[0351] Similar to the preparation procedure of intermediate II-1.2, intermediate II-110.3 was reacted with N-chlorosuccinimide to prepare intermediate II-110.4.

[0352] Step 5: Preparation of intermediate II-110.5:

[0353] At room temperature, intermediate II-110.4 (6.0 g, 25.0 mmol) and isopropanol (20 mL) were added to a 50 mL reaction flask. Then, methyl 2-(chloromethyl)acrylate (2.9 g, 25.0 mmol) and sodium bicarbonate (10.4 g, 124.1 mmol) were added, and the mixture was heated to 50 °C and reacted for 3 h. After the reaction was complete, intermediate II-110.5 (white solid, 1.4 g) was purified by column chromatography.

[0354] Step 6: Preparation of Intermediate II-110.6

[0355] Intermediate II-110.5 (785 mg, 2.3 mmol) was dissolved in dichloromethane (10 mL), and diethylaminosulfur trifluoride (DAST) (939 mg, 5.8 mmol) was added dropwise at 0 °C. The mixture was then placed in a microwave reactor and reacted at 60 °C for 10 hours. After the reaction was complete, the reaction solution was added to a saturated sodium bicarbonate aqueous solution and extracted twice with dichloromethane. The solution was dried over anhydrous sodium sulfate, the solvent was removed by vacuum distillation, and the mixture was purified by column chromatography to obtain intermediate II-110.6 (white solid, 700 mg).

[0356] Step 7: Preparation of Intermediate II-110

[0357] At room temperature, intermediate II-110.6 (700 mg, 2.06 mmol) and tetrahydrofuran (20 mL) were added to a 100 mL single-necked flask, stirred to dissolve, and then 20% lithium hydroxide monohydrate aqueous solution (95 mg, 2.27 mmol) was added. The reaction was carried out at room temperature for 1 hour. After the reaction was completed, the pH of the system was adjusted to 1-2 with dilute hydrochloric acid (10%), extracted with ethyl acetate, dried over anhydrous sodium sulfate, and the solvent was removed by vacuum evaporation to obtain intermediate II-110 (yellow solid, 650 mg). 1 H NMR (400MHz, DMSO) δ13.87(s,1H),7.68–7.09(m,4H),4.95–4.58(m,2H),3.82(dd,J=17.9,1.9Hz,1H),3.61(dd,J=17.9,1.9Hz,1H).

[0358] Example 10

[0359] Preparation of intermediate II-115

[0360] Step 1: Preparation of intermediate II-115.1:

[0361] Similar to the preparation procedure of intermediate II-110.5, intermediate II-1.2 was reacted with methyl 2-(hydroxymethyl)acrylate to prepare intermediate II-115.1.

[0362] Step 2: Preparation of intermediate II-115.2:

[0363] At room temperature, intermediate II-115.1 (1.5 g, 5.5 mmol), Dess-Martin periodinane (2.8 g, 6.6 mmol), and dichloromethane (15 mL) were added to a 100 mL single-necked flask and reacted for 30 min. After the reaction was completed, the reaction system was quenched with 30 mL of saturated sodium bicarbonate aqueous solution, and the solid suspension was removed by filtration. The filtrate was extracted twice with 30 mL of dichloromethane, and the organic phases were combined and purified by column chromatography to obtain intermediate II-115.2 (white solid, 1.1 g).

[0364] Step 3: Preparation of intermediate II-115.3:

[0365] At room temperature, intermediate II-115.2 (1.1 g, 4.1 mmol), diethylaminosulfur trifluoride (DAST) (2 g, 12.3 mmol), and dichloromethane (15 mL) were added to a 100 mL single-necked flask. After stirring thoroughly, the mixture was refluxed at 50 °C for 24 hours. After the reaction was completed, the reaction system was quenched with 30 mL of saturated sodium bicarbonate aqueous solution at room temperature, and extracted twice with 30 mL of dichloromethane. The organic phases were combined and purified by reverse-phase column chromatography to obtain intermediate II-115.3 (yellow oil, 700 mg).

[0366] Step 4: Preparation of intermediate II-115:

[0367] At room temperature, intermediate II-115.3 (700 mg, 2.4 mmol), tetrahydrofuran (5 mL), and water (20 mL) were added to a 100 mL single-necked flask and stirred until homogeneous. Lithium hydroxide monohydrate (111 mg, 2.6 mmol) was then added to the system, and the reaction was allowed to proceed for 30 min. After the reaction was complete, 1 M hydrochloric acid was added dropwise to adjust the pH to 3–4. The mixture was extracted with 20 mL of ethyl acetate, and the combined organic phases were washed once with saturated brine, dried over anhydrous sodium sulfate, and the solvent was removed by vacuum evaporation to obtain II-115 (yellow solid, 650 mg). 1H NMR (400MHz, DMSO) δ14.43 (s, 1H), 7.46 (ddd, J = 12.1, 6.7, 2.2Hz, 3H), 6.54 (t, J = 53.9Hz, 1H), 4.01-3.81 (m, 2H).

[0368] Example 11

[0369] Preparation of intermediate II-136

[0370] Step 1: Preparation of intermediate II-136.1:

[0371] At room temperature, 3,5-dichlorobenzaldehyde (5 g, 28.6 mmol), hydroxylamine hydrochloride (3.17 g, 45.8 mmol), sodium acetate (4.69 g, 57.2 mmol), and ethanol (30 mL) were added to a 100 mL single-necked flask, stirred thoroughly, and reacted at room temperature for 1.5 h. After the reaction was complete, the solvent was removed under reduced pressure, and the mixture was extracted twice with 30 mL of dichloromethane. The combined organic phases were washed once with saturated brine. The mixture was dried over anhydrous sodium sulfate, and the solvent was removed under reduced pressure to give intermediate II-136.1 (white solid, 5.4 g).

[0372] Step 2: Preparation of intermediate II-136.2:

[0373] At room temperature, intermediate II-136.1 (5.4 g, 28.4 mmol) and N,N-dimethylformamide (10 mL) were added to a 50 mL single-necked flask and stirred in an ice bath. N-chlorosuccinimide (4.5 g, 34.1 mmol) was added, and the reaction was continued in an ice bath for 3 h. After the reaction was complete, the system was extracted twice with 30 mL of dichloromethane, and the combined organic phases were washed once with saturated brine. The mixture was dried over anhydrous sodium sulfate, and the solvent was removed by vacuum distillation to give intermediate II-136.2 (white solid, 6.1 g).

[0374] Step 3: Preparation of intermediate II-136.3:

[0375] Similar to the preparation procedure of intermediate II-1.4, intermediate II-136.2 was reacted with intermediate II-1.3 to prepare intermediate II-136.3.

[0376] Step 4: Preparation of intermediate II-136.4:

[0377] At room temperature, intermediate II-136.3 (1.5 g, 4.72 mmol) and dichloromethane (10 mL) were added to a 50 mL single-necked flask and stirred until homogeneous. The system was then stirred at -10 °C for 20 min. Subsequently, Dess-Martin periodinane (3 g, 7.08 mmol) was slowly added to the system. After the addition was complete, the system was transferred to room temperature and stirred for 2 h. After the reaction was completed, the reaction system was quenched with 30 mL of saturated sodium bicarbonate and extracted twice with 30 mL of dichloromethane. The organic phases were combined and purified by reverse-phase column chromatography to obtain intermediate II-136.4 (white solid, 1.35 g).

[0378] Step 5: Preparation of intermediate II-136.5:

[0379] At room temperature, intermediate II-136.4 (1.0 g, 3.16 mmol) and dichloromethane (10 mL) were added to a 50 mL single-necked flask. The mixture was cooled to -10 °C, and diethylaminosulfur trifluoride (DAST) (1.27 g, 7.9 mmol) was slowly added dropwise. After the addition was complete, the mixture was refluxed at 40 °C for 5 hours. After the reaction was completed, the reaction system was quenched with 30 mL of saturated sodium bicarbonate, and the mixture was extracted twice with 30 mL of dichloromethane. The organic phases were combined, the solvent was removed under reduced pressure, and the mixture was purified by column chromatography to obtain intermediate II-136.5 (a pale yellow solid, 500 mg).

[0380] Step 6: Preparation of intermediate II-136:

[0381] At room temperature, intermediate II-136.5 (500 mg, 1.48 mmol), tetrahydrofuran (5 mL), and water (20 mL) were added to a 100 mL single-necked flask and stirred until homogeneous. Lithium hydroxide monohydrate (68 mg, 1.6 mmol) was then added to the system, and the reaction was allowed to proceed for 30 minutes. After the reaction was complete, 1 M hydrochloric acid was added dropwise to adjust the pH to 3–4. The mixture was extracted with 20 mL of ethyl acetate, and the combined organic phases were washed once with saturated brine, dried over anhydrous sodium sulfate, and the solvent was removed by vacuum evaporation to obtain II-136 (white solid, 450 mg). 1 H NMR (400MHz, DMSO) δ7.77 (s, 3H), 3.98 (d, J = 1.6Hz, 2H), 1.94-1.77 (m, 3H).

[0382] Example 12

[0383] Preparation of intermediate II-155:

[0384] Step 1: Preparation of intermediate II-155.1:

[0385] At room temperature, intermediate II-136.4 (1.0 g, 3.16 mmol) and dichloromethane (10 mL) were added to a 50 mL microwave-safe reaction flask. The mixture was cooled to -10 °C and stirred. Diethylaminosulfur trifluoride (DSAT) (1.27 g, 7.9 mmol) was slowly added dropwise. After the addition was complete, the flask was placed in a microwave reactor and reacted at 60 °C for 5 hours. After the reaction was completed, the reaction system was quenched with 30 mL of saturated sodium bicarbonate, and the mixture was extracted twice with 30 mL of dichloromethane. The organic phases were combined, the solvent was removed under reduced pressure, and the mixture was purified by column chromatography to obtain intermediate II-136.5 (yellow oil, 540 mg).

[0386] Step 2: Preparation of intermediate II-155:

[0387] At room temperature, intermediate II-136.5 (540 mg, 1.7 mmol), tetrahydrofuran (5 mL), and water (20 mL) were added to a 100 mL single-necked flask and stirred until homogeneous. Lithium hydroxide monohydrate (78 mg, 1.9 mmol) was then added to the system, and the reaction was allowed to proceed for 30 min. After the reaction was complete, hydrochloric acid (1 M) was added dropwise to adjust the pH to 3–4. The mixture was extracted with 20 mL of ethyl acetate, and the combined organic phases were washed once with saturated brine, dried over anhydrous sodium sulfate, and the solvent was removed under reduced pressure to obtain II-155 (white solid, 510 mg). 1 H NMR (400MHz, CDCl3) δ10.65(s,1H),7.34(dd,J=53.4,2.0Hz,3H),5.08-4.77(m,2H),3.92(d,J=17.4Hz,1H),3.56(d,J=17.4Hz,1H).

[0388] Following the method described above, other intermediates II can be obtained using correspondingly substituted benzaldehydes. These substituted benzaldehydes are commercially available or can be easily prepared by those skilled in the art. The prepared intermediates II and their... 1 The H NMR values ​​are shown in Table A.

[0389] Table A

[0390] The intermediate (II) prepared above can be separated into enantiomers, namely the S configuration and the R configuration, by chiral column separation.

[0391] Analytical separation methods:

[0392] Method A:

[0393] Instrument: Agilent 1260 Infinity II

[0394] Column: Chiralpak AD-H, 250×4.6mm ID, 5μm

[0395] Mobile phase: A represents n-hexane (0.2% formic acid), B represents isopropanol, isocratic rate: B% = 25%

[0396] Flow rate: 1.0 mL / min, column temperature: 30℃

[0397] Wavelength: 265nm

[0398] Running time: 20 minutes

[0399] Method B:

[0400] Instrument: Agilent 1260 Infinity II

[0401] Column: Chiralpak AD-H, 250×4.6mm ID, 5μm

[0402] Mobile phase: A represents n-hexane (0.2% formic acid), B represents isopropanol, isocratic rate: B% = 20%

[0403] Flow rate: 1.0 mL / min, column temperature: 30℃

[0404] Wavelength: 265nm

[0405] Running time: 20 minutes

[0406] Method C:

[0407] Instrument: Agilent 1260 Infinity II

[0408] Column: Chiralpak AD-H, 250×4.6mm ID, 5μm

[0409] Mobile phase: A represents n-hexane (0.2% formic acid), B represents isopropanol, isocratic rate: B% = 15%

[0410] Flow rate: 1.0 mL / min, column temperature: 30℃

[0411] Wavelength: 265nm

[0412] Running time: 20 minutes

[0413] Method D:

[0414] Instrument: Agilent 1260 Infinity

[0415] Column: Chiralpak AD-H, 250×4.6mm ID, 5μm

[0416] Mobile phase: A represents n-hexane (0.05% trifluoroacetic acid), B represents isopropanol, isocratic rate: B% = 12%

[0417] Flow rate: 1.0 mL / min, column temperature: 30℃

[0418] Wavelength: 265nm

[0419] Running time: 20 minutes

[0420] Method E:

[0421] Instrument: Agilent 1260 Infinity

[0422] Column: Chiralpak AD-H, 250×4.6mm ID, 5μm

[0423] Mobile phase: A represents n-hexane, B represents isopropanol, isocratic rate: B% = 25%

[0424] Flow rate: 1.0 mL / min, column temperature: 30℃

[0425] Wavelength: 265nm

[0426] Running time: 20 minutes

[0427] Method F:

[0428] Instrument: Agilent 1260 Infinity

[0429] Column: Chiralpak AD-H, 250×4.6mm ID, 5μm

[0430] Mobile phase: A represents n-hexane, B represents isopropanol, isocratic rate: B% = 30%

[0431] Flow rate: 1.0 mL / min, column temperature: 30℃

[0432] Wavelength: 265nm

[0433] Running time: 20 minutes

[0434] Method G:

[0435] Instrument: Agilent 1260 Infinity

[0436] Column: Chiralpak AD-H, 250×4.6mm ID, 5μm

[0437] Mobile phase: A represents n-hexane, B represents isopropanol, isocratic rate: B% = 10%

[0438] Flow rate: 1.0 mL / min, column temperature: 30℃

[0439] Wavelength: 265nm

[0440] Running time: 20 minutes

[0441] Method H:

[0442] Instrument: Agilent 1260 Infinity

[0443] Column: Chiralpak AD-H, 250×4.6mm ID, 5μm

[0444] Mobile phase: A represents n-hexane, B represents isopropanol, isocratic rate: B% = 25%

[0445] Flow rate: 1.0 mL / min, column temperature: 30℃

[0446] Wavelength: 265nm

[0447] Running time: 20 minutes

[0448] Preparative separation methods:

[0449] Method 1:

[0450] Instrument: Gilson GX-281

[0451] Column: Chiralpak AD-H, 250×30mm ID, 5μm

[0452] Mobile phase: A represents n-hexane (0.2% formic acid), B represents isopropanol, isocratic rate: B% = 25%

[0453] Flow rate: 31 mL / min, column temperature: 30℃

[0454] Wavelength: 265nm

[0455] Running time: 20 minutes

[0456] Method 2:

[0457] Instrument: Gilson GX-281

[0458] Column: Chiralpak AD-H, 250×30mm ID, 5μm

[0459] Mobile phase: A represents n-hexane (0.2% formic acid), B represents isopropanol, isocratic rate: B% = 20%

[0460] Flow rate: 33 mL / min, column temperature: 30℃

[0461] Wavelength: 265nm

[0462] Running time: 20 minutes

[0463] Method 3:

[0464] Instrument: Gilson GX-281

[0465] Column: Chiralpak AD-H, 250×30mm ID, 5μm

[0466] Mobile phase: A represents n-hexane (0.2% formic acid), B represents isopropanol, isocratic rate: B% = 15%

[0467] Flow rate: 34 mL / min, column temperature: 30℃

[0468] Wavelength: 265nm

[0469] Running time: 20 minutes

[0470] Method 4:

[0471] Instrument: Gilson GX-281

[0472] Column: Chiralpak AD-H, 250×30mm ID, 5μm

[0473] Mobile phase: A represents n-hexane (0.05% trifluoroacetic acid), B represents isopropanol; gradient: B% = 12%; flow rate: 34 mL / min; column temperature: 30℃

[0474] Wavelength: 265nm

[0475] Running time: 20 minutes

[0476] Intermediate II-1 can be isolated to give enantiomers II-1-A and II-1-B (Method 1):

[0477] Weigh 5.0 g of intermediate II-1 (purity 95%), dissolve the sample in n-hexane:isopropanol = 75:25 to prepare a 40 mg / mL solution, and inject the sample in 5 mL. After separation, intermediate II-1-A (2.36 g, purity 98%) and intermediate II-1-B (2.13 g, purity 99%) were obtained.

[0478] II-1-A: Retention time: 8.82 min (Method 1), 100 ee% (Method A) (c=0.130,in MeOH).

[0479] II-1-B: Retention time: 6.19 min (Method 1), 100% ee (Method A) (c=0.181,in MeOH).

[0480] Using the above method, other single chiral isomers of intermediate II can be obtained, and some intermediates (II) are shown in Table B.

[0481] Table B

[0482] Preparation Examples 1-2

[0483] Preparation of compound I-2

[0484] Step 1: Preparation of intermediate I-2.1:

[0485] At room temperature, commercially available methyl (1S,4R)-4-(tert-butoxycarbonylamino)-cyclopent-2-enyl-1-carboxylate (CAS NO: 168683-02-1) (500 mg, 2.07 mmol) and dichloromethane (10 mL) were added to a reaction flask. The mixture was cooled to 0 °C, and a 1 M solution of diethylzinc in n-hexane (1 M) (10.35 mL, 10.35 mmol) was added. The mixture was stirred at 0 °C for 15 min, and then diiodomethane (834 μL, 10.35 mmol) was added dropwise. After the addition was complete, the reaction was carried out at 0 °C for 30 min, and then at room temperature for 16 h. After the reaction was completed, the mixture was quenched with saturated ammonium chloride solution, extracted with dichloromethane, and the organic phase was desolventized to obtain crude intermediate I-2.1, which could be used directly in the next reaction without purification.

[0486] Step 2: Preparation of intermediate I-2.2:

[0487] At room temperature, dichloromethane (5 mL) and a 1,4-dioxane solution (7 M) (5 mL) of hydrogen chloride were added to crude intermediate I-2.1 from step 1. The mixture was reacted at room temperature for 2 h. After the reaction was completed, the mixture was filtered, the filter cake was washed with petroleum ether, and the filter cake was dried to obtain intermediate I-2.2 (200 mg, white solid).

[0488] Step 3: Preparation of intermediate I-2.3:

[0489] At room temperature, compound (S)-3-(3,5-difluorophenyl)-5-vinyl-4,5-dihydroisoxazole-5-carboxylic acid (200 mg, 0.79 mmol) and dichloromethane (5 mL) were added to a reaction flask, followed by 2 drops of N,N-dimethylformamide, and then oxaloyl chloride (100 μL, 1.18 mmol). A vigorous gas release was observed. The mixture was stirred at room temperature for 2 hours, and then the solvent and excess oxaloyl chloride were evaporated under reduced pressure. The resulting crude intermediate I-2.3 was used in the next step without further purification.

[0490] Step 4: Preparation of compound I-2:

[0491] At room temperature, intermediate I-2.2 (200 mg, 1.04 mmol), triethylamine (527 mg, 5.22 mmol), and 5 mL of dichloromethane were added to a 25 mL single-necked flask. Intermediate I-2.3 was added at 0 °C. The mixture was stirred for 2 h while being heated to room temperature. After the reaction was completed, the solvent was removed by vacuum distillation, and the mixture was purified by reverse phase preparation to obtain compound I-2 (white solid, 300 mg). 1 H NMR (400MHz, DMSO) δ8.06(d,J=7.9Hz,1H),7.40(dd,J=18.0,8.9Hz,3H),6.16(dd,J=17.3,10.6H z,1H),5.40(d,J=17.3Hz,1H),5.31(d,J=10.7Hz,1H),4.48–4.34(m,1H),3.88(d,J=17.7Hz,1H) ,3.60(s,3H),3.54(d,J=17.8Hz,1H),3.07–2.97(m,1H),1.84–1.71(m,1H),1.58(dd,J=23.6,10 .9Hz,1H),1.49(dd,J=7.6,3.9Hz,2H),0.83(dd,J=9.8,5.8Hz,1H),0.29(dd,J=13.3,7.5Hz,1H).

[0492] Preparation Examples 1-20

[0493] Preparation of compound I-20

[0494] Step 1: Preparation of intermediate I-20.1:

[0495] At room temperature, 264 mg (1.87 mmol) of commercially available (1S,4R)-4-aminocyclopentan-2-ene-1-carboxylic acid methyl ester hydrochloride (CAS NO: 77745-25-6), triethylamine (379 mg, 3.75 mmol), and 5 mL of dichloromethane were added to a 25 mL single-necked flask. Intermediate I-2.3, dissolved in 20 mL of dichloromethane, was added at 0 °C. The mixture was stirred for 2 h while being heated to room temperature. After the reaction was complete, water and dichloromethane were added, and the mixture was extracted and separated. The organic phase was dried over anhydrous sodium sulfate and concentrated under reduced pressure. Then, the mixture was purified by reverse-phase reaction to give intermediate I-20.1 (white solid, 450 mg).

[0496] Step 2: Preparation of intermediate I-20.2:

[0497] At room temperature, intermediate I-20.1 (450 mg, 1.2 mmol) and tetrahydrofuran (10 mL) were added to a reaction flask, followed by water (1 mL). The system was cooled to -5 °C, and lithium hydroxide (40.6 mg, 1.7 mmol) was added. The reaction was carried out for 5 h. After the reaction was completed, dilute hydrochloric acid was added to the system to adjust the pH to 5-6. The mixture was then extracted with ethyl acetate, dried over anhydrous sodium sulfate, and the solvent was removed by vacuum evaporation to obtain intermediate I-20.2 (400 mg, white solid).

[0498] Step 3: Preparation of intermediate I-20.3:

[0499] At room temperature, intermediate I-20.2 (400 mg, 1.1 mmol) and dichloromethane (5 mL) were added to a 50 mL single-necked flask, followed by oxalyl chloride (190 mg, 1.5 mmol), and finally 3 drops of N,N-dimethylformamide were slowly added dropwise. A large amount of gas was released during the addition. The mixture was stirred at room temperature for 0.5 h, and then the solvent and excess oxalyl chloride were evaporated under reduced pressure. The resulting crude intermediate I-20.3 was used in the next step without further purification.

[0500] Step 4: Preparation of intermediate I-20.4:

[0501] At room temperature, ethylamine hydrochloride (135 mg, 1.65 mmol), triethylamine (505.95 mg, 5.00 mmol), and dichloromethane (5 mL) were added to a 25 mL single-necked flask. At 0 °C, a dichloromethane solution of intermediate I-20.3 (210.75 mg, 0.58 mmol) was added dropwise. The reaction mixture was then allowed to rise to room temperature and stirred for 2 h. After the reaction was complete, water and dichloromethane were added, and the mixture was extracted and separated. The organic phase was dried over anhydrous sodium sulfate and concentrated under reduced pressure. The mixture was then purified by reverse-phase reaction to give intermediate I-20.4 (white solid, 380 mg).

[0502] Step 5: Preparation of compound I-20:

[0503] At room temperature, intermediate I-20.4 (380 mg, 0.98 mmol), m-chloroperoxybenzoic acid (75%) (233 mg, 1.02 mmol), and dichloromethane (5 mL) were added to a 100 mL single-necked flask. The mixture was stirred at room temperature for 24 h. After the reaction was complete, the mixture was extracted twice with 100 mL of ethyl acetate. The combined organic phases were washed once with saturated brine. The mixture was dried over anhydrous sodium sulfate, and the solvent was removed under reduced pressure. The residue was purified by column chromatography to give compound I-20 (white solid, 300 mg). 1 H NMR (400MHz, CDCl3) δ7.17 (dd, J=7.9, 2.2Hz, 2H), 7.06 (d, J=9.9Hz, 1H), 6.89 (tt, J=8.6, 2.3H z,1H),6.26(t,J=5.3Hz,1H),6.14(dd,J=17.2,10.7Hz,1H),5.52(d,J=17.2Hz,1H),5.33(d,J= 10.8Hz,1H),4.61–4.48(m,1H),3.88(d,J=17.2Hz,1H),3.66(s,1H),3.41–3.18(m,3H),2.84(d d,J=15.4,7.6Hz,1H),2.27–2.18(m,2H),1.93(dd,J=31.4,15.3Hz,2H),1.15(t,J=7.3Hz,3H).

[0504] Preparation Examples 1-63

[0505] Preparation of compound I-63

[0506] Step 1: Preparation of intermediate I-63.1:

[0507] At room temperature, compound (S)-3-(3-chloro-5-trifluoromethyl)phenyl)-5-vinyl-4,5-dihydroisoxazole-5-carboxylic acid (400 mg, 1.25 mmol) and dichloromethane (5 mL) were added to a 25 mL single-necked flask, followed by 2 drops of N,N-dimethylformamide (DMF), and then oxaloyl chloride (238.25 mg, 1.87 mmol). A vigorous gas release was observed. The mixture was stirred at room temperature for 2 hours, and then the solvent and excess oxaloyl chloride were evaporated under reduced pressure. The resulting crude intermediate I-63.1 was used for the next step without further purification.

[0508] Step 2: Preparation of intermediate I-63.2

[0509] At room temperature, commercially available (1S,4R)-4-aminocyclopentan-2-ene-1-carboxylic acid methyl ester hydrochloride (CAS NO: 77745-25-6) (264 mg, 1.87 mmol), triethylamine (379 mg, 3.75 mmol), and 5 mL of dichloromethane were added to a 25 mL single-necked flask. Intermediate I-63.1, dissolved in 20 mL of dichloromethane, was added at 0 °C. The mixture was stirred for 2 h while being heated to room temperature. After the reaction was complete, water and dichloromethane were added, and the mixture was extracted and separated. The organic phase was dried over anhydrous sodium sulfate and concentrated under reduced pressure. Then, reverse-phase purification was performed to obtain intermediate I-63.2 (white solid, 450 mg). 1 H NMR(400MHz,DMSO)δ8.13(d,J=7.8Hz,1H),8.07–8.03(m,1H),8.01(d,J=1.6Hz,1H),7.97 (d,J=2.0Hz,1H),6.24–6.10(m,1H),5.94–5.86(m,1H),5.85–5.78(m,1H),5.41(dd,J=17. 2,1.0Hz,1H),5.31(dd,J=10.6,1.0Hz,1H),4.85–4.75(m,1H),3.97(d,J=17.8Hz,1H),3.6 5(d,J=18.3Hz,1H),3.63(s,3H),3.59–3.51(m,1H),2.48–2.35(m,1H),1.93–1.77(m,1H).

[0510] Step 3: Preparation of compound I-63:

[0511] At room temperature, intermediate I-63.2 (450 mg, 1.02 mmol), m-chloroperoxybenzoic acid (75%) (233 mg, 1.02 mmol), and dichloromethane (5 mL) were added to a 100 mL single-necked flask. The mixture was stirred at room temperature for 24 h. After the reaction was complete, the mixture was extracted twice with 100 mL of ethyl acetate. The combined organic phases were washed once with saturated brine. The mixture was dried over anhydrous sodium sulfate, and the solvent was removed under reduced pressure. The residue was purified by column chromatography to give compound I-63 (white solid, 360 mg). 1 H NMR (400MHz, DMSO) δ8.27(d,J=6.8Hz,1H),8.04(d,J=14.0Hz,2H),7.97(s,1 H),6.26–6.12(m,1H),5.43(d,J=17.2Hz,1H),5.33(d,J=10.6Hz,1H),4.20( q,J=8.0Hz,1H),3.97(d,J=17.8Hz,1H),3.71–3.66(m,2H),3.64(s,3H),3.6 0–3.56(m,1H),3.10(t,J=9.4Hz,1H),2.01–1.87(m,1H),1.63–1.49(m,1H).

[0512] Preparation Examples 1-65

[0513] Preparation of compound I-65

[0514] Step 1: Preparation of intermediate I-65.1:

[0515] At room temperature, intermediate I-63.2 (500 mg, 1.13 mmol) and tetrahydrofuran (10 mL) were added to a reaction flask, followed by water (1 mL). The system was cooled to -5 °C, and lithium hydroxide (40.6 mg, 1.7 mmol) was added. The reaction was carried out for 5 h. After the reaction was completed, dilute hydrochloric acid was added to the system to adjust the pH to 5-6. The mixture was then extracted with ethyl acetate, dried over anhydrous sodium sulfate, and the solvent was removed by vacuum evaporation to obtain intermediate I-65.1 (470 mg, white solid).

[0516] Step 2: Preparation of intermediate I-65.2:

[0517] At room temperature, intermediate I-65.1 (470 mg, 1.1 mmol) and dichloromethane (5 mL) were added to a 50 mL single-necked flask, followed by oxalyl chloride (190 mg, 1.5 mmol). Finally, 3 drops of N,N-dimethylformamide were slowly added dropwise, during which a large amount of gas was released. The mixture was stirred at room temperature for 0.5 h, and then the solvent and excess oxalyl chloride were evaporated under reduced pressure. The resulting crude intermediate I-65.2 was used in the next step without further purification.

[0518] Step 3: Preparation of intermediate I-65.3:

[0519] At room temperature, 1 mL of n-propanol and 5 mL of dichloromethane were added to a 50 mL single-necked flask and stirred. Then, at 0 °C, a 2 mL solution of dichloromethane of intermediate I-65.2 obtained in the previous step was slowly added dropwise to the system. The mixture was stirred at room temperature for 1 h. LC-MS was used to monitor the complete disappearance of the reactants. After the reaction was completed, 15 mL of water and 10 mL of dichloromethane were added to the system, and the mixture was extracted and separated. The organic phase was dried over anhydrous sodium sulfate and concentrated under reduced pressure to obtain crude intermediate I-65.3 (white solid, 460 mg).

[0520] Step 4: Preparation of compound I-65:

[0521] At room temperature, intermediate I-65.3 (460 mg, 0.98 mmol), m-chloroperoxybenzoic acid (75%) (233 mg, 1.02 mmol), and dichloromethane (5 mL) were added to a 100 mL single-necked flask. The mixture was stirred at room temperature for 24 h. After the reaction was complete, the mixture was extracted twice with 100 mL of ethyl acetate. The combined organic phases were washed once with saturated brine. The mixture was dried over anhydrous sodium sulfate, and the solvent was removed under reduced pressure. The residue was purified by column chromatography to give compound I-65 (white solid, 350 mg). 1H NMR (400MHz, CDCl3) δ7.83(s,1H),7.77(s,1H),7.67(s,1H),7.02(d,J=8.5Hz,1H),6.25–6.10 (m,1H),5.57(d,J=17.2Hz,1H),5.38(d,J=10.7Hz,1H),4.52–4.39(m,1H),4.14–4.08(m,2H), 3.96(d,J=17.2Hz,1H),3.80–3.73(m,1H),3.61–3.53(m,1H),3.37(d,J=17.3Hz,1H),2.99–2. 90(m,1H),2.22–2.09(m,1H),1.68(d,J=7.3Hz,2H),1.61–1.47(m,1H),0.95(t,J=7.4Hz,3H).

[0522] Preparation Examples 1-80

[0523] Preparation of compound I-80

[0524] Step 1: Preparation of intermediate I-80.1:

[0525] At room temperature, compound (R)-3-(3,5-dichlorophenyl)-5-methyl-4,5-dihydroisoxazole-5-carboxylic acid (274 mg, 1.0 mmol) and dichloromethane (4 mL) were added to a 50 mL single-necked flask, followed by oxalyl chloride (190 mg, 1.5 mmol, 1.5 equiv). Finally, 3 drops of N,N-dimethylformamide were slowly added dropwise, releasing a large amount of gas during the addition. The mixture was stirred at room temperature for 0.5 h, and then the solvent and excess oxalyl chloride were evaporated under reduced pressure. The resulting crude intermediate I-80.1 was used for the next step without further purification.

[0526] Step 2: Preparation of intermediate I-80.2:

[0527] At room temperature, commercially available (1S,4R)-4-aminocyclopentan-2-ene-1-carboxylic acid methyl ester hydrochloride (CAS NO: 77745-25-6) (263 mg, 1.5 mmol), triethylamine (404 mg, 4.0 mmol), and dichloromethane (5 mL) were added to a 50 mL single-necked flask. The system was stirred at room temperature for 20 min. Then, at 0 °C, a dichloromethane solution (2 mL) of intermediate I-80.1 obtained in the previous step was slowly added dropwise to the system. The mixture was stirred at room temperature for 1.5 h. LC-MS was used to monitor the complete disappearance of the reactants. After the reaction was complete, water (15 mL) and dichloromethane (10 mL) were added to the system, and the mixture was extracted and separated. The organic phase was dried over anhydrous sodium sulfate and concentrated under reduced pressure to obtain crude intermediate I-80.2 (light yellow solid, 360 mg), which was used directly in the next step without further purification.

[0528] Step 3: Preparation of intermediate I-80.3:

[0529] At room temperature, intermediate I-80.2 (360 mg, 0.906 mmol) and tetrahydrofuran (10 mL) were added to a reaction flask, followed by water (1 mL). The system was cooled to -5 °C, and lithium hydroxide (40.6 mg, 1.7 mmol) was added. The reaction was carried out for 5 h. After the reaction was completed, dilute hydrochloric acid was added to the system to adjust the pH to 5-6. The mixture was then extracted with ethyl acetate, dried over anhydrous sodium sulfate, and the solvent was removed by vacuum evaporation to obtain intermediate I-80.3 (300 mg, white solid).

[0530] Step 4: Preparation of compound I-80:

[0531] At room temperature, intermediate I-80.3 (300 mg, 0.78 mmol), m-chloroperoxybenzoic acid (75%) (233 mg, 1.02 mmol), and dichloromethane (5 mL) were added to a 100 mL single-necked flask. The mixture was stirred at room temperature for 24 h. After the reaction was complete, the mixture was extracted twice with 100 mL of ethyl acetate. The combined organic phases were washed once with saturated brine. The mixture was dried over anhydrous sodium sulfate, and the solvent was removed under reduced pressure. The residue was purified by column chromatography to give compound I-80 (white solid, 240 mg). 1H NMR (400MHz, CDCl3) δ7.51(d,J=1.9Hz,2H),7.43–7.40(m,1H),7.10(d,J=8.6Hz,1H),4.51–4.39(m,1H),3.81–3.79(m,1H),3.76( d,J=17.6Hz,1H),3.63–3.58(m,1H),3.19(d,J=17.3Hz,1H),3.04–2.95(m,1H),2.24–2.11(m,1H),1.75(s,3H),1.59–1.48(m,1H).

[0532] Preparation Examples 1-81

[0533] Preparation of compound I-81

[0534] Step 1: Preparation of compound I-81:

[0535] At room temperature, intermediate I-80.2 (360 mg, 0.9 mmol), m-chloroperoxybenzoic acid (75%) (249 mg, 1.1 mmol), and dichloromethane (5 mL) were added to a 50 mL single-necked flask. The system was stirred at room temperature for 5 h, and LC-MS was used to monitor the complete disappearance of the reactants. After the reaction was completed, the reaction system was diluted with water (20 mL) and dichloromethane (15 mL), extracted, and separated. The organic phase was dried over anhydrous sodium sulfate, and the solvent was removed under reduced pressure. The residue was separated by normal-phase column chromatography (dichloromethane / methanol) to obtain the target compound I-81 (white solid, 290 mg). 1 H NMR (400MHz, CDCl3) δ7.46(d,J=1.9Hz,2H),7.35(t,J=1.9Hz,1H),7.13(d,J=8.5Hz,1H),4.48–4.26(m,1H),3.80–3.63(m,5H),3.55(dd ,J=2.8,1.4Hz,1H),3.16(d,J=17.3Hz,1H),2.93–2.88(m,1H),2.09(dt,J=13.0,8.3Hz,1H),1.70(s,3H),1.50(dt,J=13.0,9.8Hz,1H).

[0536] Preparation Examples 1-132

[0537] Preparation of compound I-132

[0538] Step 1: Preparation of intermediate I-132.1:

[0539] At room temperature, compound (R)-3-(3-(difluoromethoxy)-5-fluorophenyl)-5-(trifluoromethyl)-4,5-dihydroisoxazole-5-carboxylic acid (200 mg, 0.58 mmol) and dichloromethane (5 mL) were added to a 25 mL single-necked flask, followed by 2 drops of N,N-dimethylformamide (DMF), and then oxaloyl chloride (110.95 mg, 0.87 mmol) was added dropwise at room temperature. A vigorous release of gas was observed. The mixture was stirred at room temperature for 2 hours, and then the solvent and excess oxaloyl chloride were evaporated under reduced pressure. The resulting crude intermediate I-132.1 was used for the next step without further purification.

[0540] Step 2: Preparation of intermediate I-132.2

[0541] At room temperature, commercially available (1S,4R)-4-aminocyclopentan-2-ene-1-carboxylic acid methyl ester hydrochloride (CAS NO: 77745-25-6) (114.92 mg, 0.65 mmol), triethylamine (303.55 mg, 3.00 mmol), and dichloromethane (5 mL) were added to a 25 mL single-necked flask. At 0 °C, a dichloromethane solution of intermediate I-132.1 (210.75 mg, 0.58 mmol) was added dropwise. The reaction mixture was then allowed to rise to room temperature and stirred for 2 h. After the reaction was complete, water and dichloromethane were added, and the mixture was extracted and separated. The organic phase was dried over anhydrous sodium sulfate and concentrated under reduced pressure. The mixture was then purified by reverse-phase reaction to obtain intermediate I-132.2 (white solid, 250 mg).

[0542] Step 3: Preparation of compound I-132:

[0543] At room temperature, intermediate I-132.2 (250 mg, 0.50 mmol), m-chloroperoxybenzoic acid (75%) (173.92 mg, 0.81 mmol), and dichloromethane (5 mL) were added to a 15 mL pressure-resistant flask. The flask was sealed and stirred at room temperature for 24 h. After the reaction was complete, dichloromethane was added, and the mixture was washed once with saturated brine. The organic phase was dried over anhydrous sodium sulfate, and the solvent was removed under reduced pressure. The residue was purified by column chromatography to give compound I-132 (white solid, 156 mg). 1H NMR (400MHz, CDCl3) δ7.24(d,J=6.1Hz,2H),7.15(d,J=8.7Hz,1H),7.05–6.92(m,1H),6.56(t,J=72.4Hz,1H),4.59–4.43(m,1H) ,3.95(d,J=18.1Hz,1H),3.78(d,J=14.8Hz,5H),3.66–3.58(m,1H),2.98(t,J=9.3Hz,1H),2.28–2.12(m,1H),1.60–1.53(m,1H).

[0544] Preparation Examples 1-169

[0545] Preparation of compound I-169

[0546] At room temperature, methyl (1S,2S,4R,5R)-4-((R)-3-(3,5-difluorophenyl)-5-methyl-4,5-dihydroisoxazole-5-carboxamido)-6-oxabicyclo[3.1.0]hexane-2-carboxylic acid (500 mg, 1.31 mmol), dimethyl thioformamide (234 mg, 2.62 mmol), and anhydrous 1,2-dichloroethane (10 mL) were added to a reaction flask, followed by the addition of a catalytic amount of trifluoroacetic acid (15 mg, 0.13 mmol). The mixture was heated to 60 °C and reacted overnight. After the reaction was complete, the system was desolvated and purified by reverse phase to give compound I-169 (300 mg, viscous solid). 1 H NMR (400MHz, DMSO) δ8.00(d,J=7.9Hz,1H),7.41(dd,J=8.3,5.4Hz,3H),4.41(t,J=7.4Hz,1H),3.72(dd,J=15.9,11.0Hz,2H),3.6 7(s,3H),3.42(dd,J=11.0,6.8Hz,2H),3.27(d,J=8.0Hz,1H),2.14(dt,J=15.0,7.6Hz,1H),1.78(d,J=14.7Hz,1H),1.58(s,3H).

[0547] The preparation was carried out similarly to the preparation examples given above, and the analytical data of some compounds in the examples are shown in Table C below.

[0548] Table C

[0549] Following similar preparation examples as described and mentioned above, and taking into account the general details relating to the preparation of substituted isoxazoline formamides, the compounds described below are obtained:

[0550] Table 2.1: Compounds 2.1-1 to 2.1-574 of the general formula (I.1) of the present invention.

[0551] Z and G are defined below.

[0552] Table 2.1

[0553] Table 2.2: Compounds 2.2-1 to 2.2-574 of the general formula (I.2) of the present invention.

[0554] Z and G are defined as shown in Table 2.1.

[0555] Table 2.3: Compounds 2.3-1 to 2.3-574 of the general formula (I.3) of the present invention.

[0556] Z and G are defined as shown in Table 2.1.

[0557] Table 2.4: Compounds 2.4-1 to 2.4-574 of the general formula (I.4) of the present invention.

[0558] Z and G are defined as shown in Table 2.1.

[0559] Table 2.5: Compounds 2.5-1 to 2.5-574 of the general formula (I.5) of the present invention.

[0560] Z and G are defined as shown in Table 2.1.

[0561] Table 2.6: Compounds 2.6-1 to 2.6-574 of the general formula (I.6) of the present invention.

[0562] Z and G are defined as shown in Table 2.1.

[0563] Table 2.7: Compounds 2.7-1 to 2.7-574 of the general formula (I.7) of the present invention.

[0564] Z and G are defined as shown in Table 2.1.

[0565] Table 2.8: Compounds 2.8-1 to 2.8-574 of the general formula (I.8) of the present invention.

[0566] Z and G are defined as shown in Table 2.1.

[0567] Table 2.9: Compounds 2.9-1 to 2.9-574 of the general formula (I.9) of the present invention.

[0568] Z and G are defined as shown in Table 2.1.

[0569] Table 2.10: Compounds 2.10-1 to 2.10-574 of the general formula (I.10) of the present invention.

[0570] Z and G are defined as shown in Table 2.1.

[0571] Table 2.11: Compounds 2.11-1 to 2.11-574 of the general formula (I.11) of the present invention.

[0572] Z and G are defined as shown in Table 2.1.

[0573] Table 2.12: Compounds 2.12-1 to 2.12-574 of the general formula (I.12) of the present invention.

[0574] Z and G are defined as shown in Table 2.1.

[0575] Table 2.13: Compounds 2.13-1 to 2.13-574 of the general formula (I.13) of the present invention.

[0576] Z and G are defined as shown in Table 2.1.

[0577] Table 2.14: Compounds 2.14-1 to 2.14-574 of the general formula (I.14) of the present invention.

[0578] Z and G are defined as shown in Table 2.1.

[0579] Table 2.15: Compounds 2.15-1 to 2.15-574 of the general formula (I.15) of the present invention.

[0580] Z and G are defined as shown in Table 2.1.

[0581] Table 2.16: Compounds 2.16-1 to 2.16-574 of the general formula (I.16) of the present invention.

[0582] Z and G are defined as shown in Table 2.1.

[0583] Table 2.17: Compounds 2.17-1 to 2.17-574 of the general formula (I.17) of the present invention.

[0584] Z and G are defined as shown in Table 2.1.

[0585] Table 2.18: Compounds 2.18-1 to 2.18-574 of the general formula (I.18) of the present invention.

[0586] Z and G are defined as shown in Table 2.1.

[0587] Table 2.19: Compounds 2.19-1 to 2.19-574 of the general formula (I.19) of the present invention.

[0588] Z and G are defined as shown in Table 2.1.

[0589] Similarly, the structures of general formulas (I.20) to (I.179) are shown in Table 3. In the specific compounds corresponding to each general formula, Z and G correspond as defined in Table 2.1 (corresponding to their numbers "-1" to "-574").

[0590] Table 3

[0591] Biological Example 1: Indoor Herbicidal Activity Assay

[0592] The herbicidal activity test method for the compounds of this invention is as follows:

[0593] Pre-emergence: Sow a measured amount of grass weeds (barnyard grass, goosegrass, green foxtail grass, crabgrass, Japanese barnyard grass, wild oat, barnyard grass, wild oat, perennial ryegrass, Kentucky bluegrass, jointed goatgrass, wild oat, large spike barnyard grass), broadleaf weeds (eggplant, amaranth, wild rapeseed, chickweed, speedwell, fleabane, sesbania, wild arrowhead, bulrush), and rice sedge seeds separately in 7cm diameter holes filled with nutrient soil (sandy soil). Sow seeds in plastic pots (pH 6.1, organic matter 1%), cover with an appropriate amount of soil, and then moisten the soil by bottom watering. Place in a constant temperature and light incubator for 24 hours before soil spraying. The spraying is performed using a 3WP-2000 mobile spray tower manufactured by the Nanjing Agricultural Mechanization Research Institute of the Ministry of Agriculture, with a main shaft speed of 96 mm / r, a spray height of 300 mm, an effective nozzle width of 350 mm, and a spray area of ​​0.35 m². 2 The nozzle flow rate is 390 mL / min.

[0594] Post-emergence: Appropriate amounts of seeds from gramineous weeds (barnyard grass, goosegrass, green foxtail, crabgrass, Japanese barnyard grass, wild oat, barnyard grass, wild oat, perennial ryegrass, Kentucky bluegrass, jointed goatgrass, wild oat, large-spike barnyard grass), broadleaf weeds (eggplant, amaranth, wild rapeseed, chickweed, speedwell, fleabane, sesbania, wild arrowhead, and bulrush), and *Symplocos edulis* were sown separately in 7cm diameter plastic pots with drainage holes at the bottom, filled with nutrient soil (sandy soil, pH 6.1, 1% organic matter). After sowing, a suitable amount of soil was covered, and the soil was moistened by bottom watering. The pots were then placed in a constant-temperature, light-controlled incubator until the 2-4 leaf stage, at which point foliar spraying was applied. After treatment, the samples were placed in a laboratory to allow the pesticide solution to air dry naturally before being placed in a constant-temperature, light-controlled incubator for 21 days. Results were measured after this period.

[0595] Grading standards for prevention and control effectiveness:

[0596] A indicates that the fresh weight inhibition rate is greater than or equal to 80% to 100%;

[0597] B indicates that the fresh weight inhibition rate is greater than or equal to 60% and less than 80%;

[0598] C indicates that the fresh weight inhibition rate is greater than or equal to 40% and less than 60%;

[0599] D indicates that the fresh weight inhibition rate is greater than or equal to 20% and less than 40%;

[0600] E indicates that the fresh weight inhibition rate is less than 20%.

[0601] Following the above testing methods, parallel experiments were conducted on some compounds of general formula (I) and control compounds to assess their herbicidal activity. The results are shown in Tables 4-1 to 4-3:

[0602] Table 4-1: Herbicidal Activity of Compounds of General Formula (I) (Pre-emergence) "-" indicates that it has not been tested.

[0603] Table 4-2: Herbicidal activity of some compounds of general formula (I) and control compounds (120 g ai / ha, pre-emergence)

[0604] Table 4-3: Herbicidal activity of some compounds of general formula (I) and control compounds (60 g ai / ha, pre-emergence)

[0605] Biological Example 2: Field Herbicidal Activity Assay

[0606] The compound (I) involved in this invention is applied to vacant land in a vineyard to control unwanted vegetation.

[0607] The experimental plots were flat with medium loam soil. The main weeds in the field included goosegrass, barnyard grass, crabgrass, water hyacinth, and fleabane. Spraying was applied before weed emergence using a herbicide-specific fan nozzle, with a water volume of 450 L / ha. Each treatment plot was 20 m². 2 The required amount of compound (I) for each cell was weighed according to the set dosage, and compound (I) was prepared into a drug solution of the corresponding volume using a two-stage dilution method.

[0608] The plant control efficacy of compound (I) against weeds was investigated 15 days after application, and the final plant control efficacy and fresh weight control efficacy of compound (I) against weeds were investigated 30 days after application.

[0609] Weed control efficacy (%) per plant (fresh weight) = (Number of weeds in control area (fresh weight) - Number of weeds in treatment area (fresh weight)) / Number of weeds in control area (fresh weight) × 100

[0610] The results show that the compounds described in this invention generally have good weed control efficacy, and can produce good weed control efficacy even at low application doses.

[0611] The above description is only a preferred embodiment of the present invention. It should be noted that those skilled in the art can make several changes and improvements without departing from the inventive concept of the present invention, and these all fall within the protection scope of the present invention.

Claims

1. A 3-phenylisoxazoline-5-carboxamide compound as shown in formula (I), its stereoisomers, and its agriculturally acceptable salts: in, R1 represents -CN or F. or Represents C1-C5 alkyl, C3-C6 cycloalkyl, C2-C5 alkenyl, C2-C5 alkynyl or C1-C5 alkoxy, each of which is substituted by m1 groups selected from halogen, -CN, -OH and C1-C5 alkoxy; G represents -OR3 or -NR4R5; R3 represents H. or Representing C1-C 12 Alkyl, C3-C7 cycloalkyl, C3-C7 cycloalkyl-C1-C8 alkyl, C2-C8 alkenyl, C2-C8 ynyl, C5-C6 cycloalkenyl, -N=(C1-C6 cycloalkyl), -N=C(C1-C5 alkyl)2, phenyl, C1-C4 alkyl-phenyl, aromatic heterocyclic, or C1-C4 alkyl-aromatic heterocyclic, each optionally surrounded by m3 groups selected from halogen, -CN, -OH, C1-C6 alkoxy, C1-C6 alkoxycarbonyl, aromatic heterocyclic, aryl, and -S(O). n Substitution of the group in R2; R4 and R5 independently represent H, -OH, and Cl-C, respectively. 12 Alkyl, C1-C3 alkoxy, C1-C6 alkoxy-C1-C3 alkyl, C1-C6 alkoxy carbonyl-C1-C6 alkyl, N(C1-C3 alkyl)2 or -S(O) n R2, or R4 and R5 together with the nitrogen atom to which they are attached form saturated or partially unsaturated or fully unsaturated five-, six-, or seven-membered rings, which may contain r carbon atoms and o oxygen atoms in addition to nitrogen atoms and are optionally substituted by m4 groups selected from halogens, C1-C6 alkyl groups, halo-C1-C6 alkyl groups, oxo groups, and -CO2R6 groups. R6 represents H. or Represents C1-C8 alkyl, C3-C6 cycloalkyl, C3-C8 alkenyl or C3-C8 alkynyl, each optionally substituted with m5 groups selected from halogen, -CN and C1-C2 alkoxy groups; Z represents any one of Z-1 to Z-7. The meanings of Z-1 to Z-7 are as follows: X3 represents H, F, Cl, Br, or I. X1 and X2 independently represent H, F, Cl, Br, I, -OH, -CN, -NO2, and -S(O), respectively. n R2 or -CO2R6, or Represents C1-C3 alkyl, C1-C3 alkoxy, C3-C4 cycloalkyl, C2-C3 alkenyl or C2-C3 alkynyl, each of which is substituted by m6 groups selected from F, Cl, Br and I; R2 represents a C1-C4 alkyl or a C3-C4 cycloalkyl, each of which is substituted by m2 groups selected from F and Cl; m1 can be 0, 1, 2, or 3; m2 can be 0, 1, 2, or 3; m3 is 0, 1, 2, 3, 4, 5, 6, 7 or 8; m4 can be 0, 1, 2, 3, 4, or 5; m5 can be 0, 1, 2, 3, 4 or 5; m6 can be 0, 1, 2, or 3; n is 0, 1, or 2; o can be 0, 1, or 2; r can be 3, 4, 5, or 6.

2. The compound of formula (I) according to claim 1, its stereoisomers, and its agriculturally acceptable salts: in, R1 represents a C1-C3 alkyl, C3-C4 cycloalkyl, C2-C3 alkenyl, C2-C3 alkynyl, or C1-C3 alkoxy group, each of which is substituted by m1 groups selected from the following groups: halogen, -CN, -OH, and C1-C2 alkoxy. G represents -OR3 or -NR4R5; R3 represents H. or Representing C1-C 10 Alkyl, C3-C6 cycloalkyl, C3-C6 cycloalkyl-C1-C6 alkyl, C2-C6 alkenyl, C5-C6 cycloalkenyl, -N=(C1-C5 cycloalkyl), -N=C(C1-C3 alkyl)2, phenyl, C1-C3 alkyl-phenyl, aromatic heterocyclic, C1-C3 alkyl-aromatic heterocyclic, or C2-C6 ynyl, each substituted by m3 groups selected from the following: F, Cl, Br, I, -CN, -OH, -S(O). n R2, C1-C4 alkoxy, aryl and aromatic heterocyclic groups; R4 and R5 independently represent H, -OH, C1-C6 alkyl, C1-C3 alkoxy, C1-C3 alkoxy, -C1-C3 alkyl, or -S(O). n R2, or R4 and R5 together with the nitrogen atom to which they are attached form a saturated or partially unsaturated or fully unsaturated five- or six-membered ring, which may contain r carbon atoms and o oxygen atoms in addition to the nitrogen atom and may optionally be substituted by m4 groups selected from halogen, C1-C6 alkyl, halogenated C1-C6 alkyl, oxo, -CO2R6. R2 represents C1-C4 alkyl; R6 represents H. or Represents C1-C6 alkyl, C3-C6 cycloalkyl, C3-C8 alkenyl or C3-C8 alkynyl, each optionally substituted with m5 groups selected from halogen, -CN and C1-C2 alkoxy groups; m1 can be 0, 1, 2, or 3; m3 is 0, 1, 2, 3, 4, 5, 6, 7 or 8; m4 can be 0, 1, 2, 3, or 4; m5 can be 0, 1, 2, or 3; n is 0, 1, or 2; o can be 0, 1, or 2; r is 3, 4, or 5.

3. The compound of formula (I) according to claim 2, its stereoisomers, and its agriculturally acceptable salts: in, R1 represents a C1-C3 alkyl, C2-C3 alkenyl, C2-C3 alkynyl, or C1-C3 alkoxy group, each of which is substituted by m1 groups selected from F, Cl, and Br. G represents -OR3 or -NR4R5; R3 represents H. or Represents C1-C7 alkyl, C3-C6 cycloalkyl, C3-C6 cycloalkyl-C1-C6 alkyl, C2-C6 alkenyl, C5-C6 cycloalkenyl, C2-C6-ynyl, C1-C3 alkoxy-C1-C3 alkyl, -N=C(C1-C3 alkyl)2, phenyl, C1-C3 alkyl-phenyl-, aromatic heterocyclic, C1-C3 alkyl-aromatic heterocyclic, phenyl-C1-C3-alkyl- or aromatic heterocyclic-C1-C3-alkyl-, each substituted by m3 groups selected from the following: F, Cl, Br, I, -CN, -OH, -OCH3 or -S(O). n R2; R4 and R5 independently represent H, -OH, C1-C6-alkyl, C1-C3 alkoxy, or -S(O). n R2; or R4 and R5 together with the nitrogen atoms they are attached to form saturated five-membered or six-membered rings, which contain four or five carbon atoms in addition to nitrogen atoms. R2 represents C1-C3 alkyl; m1 can be 0, 1, 2, or 3; m3 is 0, 1, 2, 3, 4, 5, 6, 7 or 8; n is 0, 1, or 2.

4. The compound of formula (I) according to claim 3, its stereoisomers, and its agriculturally acceptable salts: in, R1 represents -CH3, -CH=CH2, -CF=CH2, -CF3, -CF2H, -CH2F, -CH2Cl, -CF2CH3, or -OCH3; G represents -OR3 or -NR4R5; R3 represents H. or Represents -CH3, -CH2CH3, -CH2CH2CH3, -CH(CH3)2, -CH2CH2CH2CH3, -CH2CH(CH3)2, -CH(CH3)CH2CH3, -C(CH3)3, -(CH2)4CH3, -(CH2)5CH3, -(CH2)6CH3, -CH2CH =CH2, -CH2CH2CH=CH2, -CH2CH=CHCH3, -CH(CH3)CH=CH2, -CH2C≡CH, (S)-CH(CH3)C≡CH, (R)-CH(CH3)C≡CH, -CH2C≡CCH3, -CH(CH2CH3)C≡CH, -CH2CH2S(O) n CH3、-CH2CH2S(O) n CH2CH3, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, -CH2-cyclopropyl, -CH2-cyclobutyl, -CH2-cyclopentyl, -CH2-cyclohexyl, -CH2CH2CN, -CH2CF3, -CH2CF2H, -CH2CH2F, -CH2CH2Cl, -CH2CH2Br, -CH2CCl3, -CH2CF2CF3, -CH2(CF2)2H, -CH2(CF2)3H, -CH2(CF2)4H, -CH2CH2OCH3, -(CH2)3OCH3, (S)-CH2CH(CH3)OCH3, (S)-CH(CH3)C H2OCH3, (R)-CH2CH(CH3)OCH3, (R)-CH(CH3)CH2OCH3, -CH2CH2OCH2CH3, -N=C(CH3)2, -C6H5, p-CH3-C6H4-, pF-C6H4-, p-Cl-C6H4-, p-Br-C6H4-, -CH2-C6H5, p-CH3-C6H4-CH2-, pF-C6H4-CH2-, p-Cl-C6H4-CH2-, p-Br-C6H4-CH2-, p-CN-C6H4-CH2-, p-CH3O-C6H4-CH2- or 3-pyridyl; n is 0, 1, or 2; R4 and R5 independently represent H, -CH3, -CH2CH3, -OH, -OCH3, -OCH2CH3, -OCH(CH3)2, or -SO2CH3. or R4 and R5, together with the nitrogen atom they are attached to, form a saturated five- or six-membered ring, which contains four or five carbon atoms in addition to the nitrogen atom.

5. The compound of formula (I) according to claim 1, its stereoisomers, and its agriculturally acceptable salts: in, Z represents Z-1, Z-2, or Z-5; X3 represents H or F; X1 and X2 each independently represent H, F, Cl, Br, or -CN. or Represents C1-C3 alkyl or C1-C3 alkoxy groups, each of which is substituted by m6 groups selected from F, Cl and Br; m6 can be 0, 1, 2, or 3.

6. The compound of formula (I) according to claim 1, its stereoisomers, and its agriculturally acceptable salts: in, Z represents Z-2; X3 represents H or F; X1 and X2 each independently represent H, F, Cl, Br, -CH3, -CN, -OCH3, -CF3, -CF2H, -OCF3, or -OCF2H.

7. A method for preparing the compound of formula (I) according to any one of claims 1-6, its stereoisomers, and agriculturally acceptable salts thereof, characterized in that, The method includes the following steps: (1) The compound of general formula (V) condenses with hydroxylamine or hydroxylamine salt to form the compound of general formula (IV); (2) The compound shown in general formula (IV) reacts with a chlorinating agent to form the compound shown in general formula (III); (3) The compound shown in general formula (III) and the compound shown in general formula (VII) are cyclized under the action of a base or undergo chiral selective cyclization under the action of a chiral catalyst to directly obtain or hydrolyze the compound shown in general formula (II). (4) The compound shown in general formula (II) reacts with the compound shown in general formula (VI) to give the 3-phenylisoxazoline-5-carboxamide compound shown in general formula (I); R7 represents H. or Representing C1-C5 alkyl, C3-C5 cycloalkyl, C2-C5 alkenyl, C2-C5 alkynyl or benzyl, each of which is substituted by m groups selected from F, Cl, Br, -CN, -OH and C1-C2 alkoxy; wherein X1, X2, X3, R1, G and Z are as defined in claims 1-6.

8. A herbicidal composition, characterized in that, It includes at least one of the compounds of formula (I) as described in any one of claims 1-6, their stereoisomers or salts thereof, wherein the active component is a compound of formula (I), and the composition contains an active component at a weight percentage of 0.1-99.9%.

9. The herbicidal composition according to claim 8 further includes formulation adjuvants.

10. The weed control composition according to claim 8, comprising at least one other active compound selected from: insecticides, acaricides, herbicides, fungicides, safeners and / or growth regulators.

11. The herbicidal composition according to claim 8, comprising a safener.

12. The herbicidal composition according to claim 11, wherein the safener is selected from pyrazolium bromide, cyclopropanesulfonamide, bis(oxazolyl) acid, quinalazine, cyclopropanesulfonamide, cyclopropanesulfonamide, dichloropropenesulfonamide, or Metcamifen.

13. A method for controlling harmful plants, characterized in that, Apply an effective amount of at least one compound of formula (I) as described in any one of claims 1-6 or the herbicidal composition as described in any one of claims 8-12 to the plant or the location where harmful plants are growing.

14. Use of the compound of formula (I) according to any one of claims 1-6 or the herbicidal composition according to any one of claims 8-12 for the control of harmful plants.

15. The use according to claim 14, characterized in that, Use of a compound of formula (I) or a herbicidal composition including a compound of formula (I) to control harmful plants in useful plant crops.

Images