A 3-phenylisoxazoline-5-carboxamide compound, a preparation method, a herbicidal composition and application thereof

Abstract

This invention relates to the field of pesticides and herbicides, and more specifically to a 3-phenylisooxazoline-5-carboxamide compound as shown in general formula (I), its stereoisomers, its agriculturally acceptable salts, its preparation method, herbicidal compositions, and its use in the field of plant protection. X1, X2, X3, R1, Z, and G are as defined herein.

Description

A 3-phenylisoxazolin-5-carboxamide compound, its preparation method, herbicide composition and application Technical Field

[0001] The present invention relates to the field of pesticide herbicides, and in particular to a 3-phenylisoxazoline-5-carboxamide compound, its stereoisomers, its agrochemically acceptable salts, a preparation method, a herbicidal composition and applications thereof. Background Art

[0002] Chemical weed control with herbicides is the most economical and effective means of weed control. However, the long-term, continuous, high-dose use of a single chemical herbicide, or one with a single mode of action, can easily lead to problems such as weed resistance and the evolution of resistance. Developing new pesticides is a key approach to addressing these issues.

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

[0004] Bayer later developed the herbicide icafolin (Compound I-31 listed in the patent specification of WO2018228985A1), which is a mixture of a pair of diastereomers:

[0005] Such herbicides are generally used in the form of agrochemically acceptable salts or esters, such as icafolin-methyl (Compound I-10 listed in the patent specification of WO2018228985A1):

[0006] WO2019145245A1 specifically discloses CK1 (listed compound I-011) and CK2 (listed compound I-012) in the specification:

[0007] WO2019034602A1 specifically discloses CK3 (listed compound I-25) and CK4 (listed compound I-26) in Table 1 of the specification:

[0008] The herbicidal activity of the compounds known from the prior art, in particular at low application rates, and / or their compatibility with crop plants still needs to be improved.

[0009] Summary of the Invention

[0010] The object of the present invention was therefore to provide compounds which have strong herbicidal activity, in particular even at low application rates, sufficiently low toxicity to humans and animals and / or high compatibility with crop plants, and which should also exhibit a broad spectrum of activity against a large number of different undesirable plants.

[0011] Surprisingly, it has now been found that 3-phenylisoxazoline-5-carboxamides of the formula (I) defined hereinafter, their stereoisomers and agrochemically acceptable salts thereof have excellent herbicidal activity against a broad spectrum of economically important monocotyledonous and dicotyledonous annual harmful plants.

[0012] Therefore, the present invention provides 3-phenylisoxazoline-5-carboxamide compounds represented by formula (I), stereoisomers thereof or agriculturally acceptable salts thereof:

[0013] in,

[0014] R1 represents -CN or F,

[0015] or

[0016] 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;

[0017] G represents -OR3 or -NR4R5;

[0018] R3 represents H,

[0019] or

[0020] Represents C1-C 12 -alkyl, C3-C7-cycloalkyl, C3-C7-cycloalkyl-C1-C8-alkyl, C2-C8-alkenyl, C2-C8-alkynyl, C5-C6-cycloalkenyl, -N=(C1-C6-cycloalkyl), -N=C(C1-C5-alkyl)2, phenyl, C1-C4-alkyl-phenyl, aromatic heterocyclyl or C1-C4-alkyl-aromatic heterocyclyl, each of which is optionally substituted by m3 units selected from halogen, -CN, -OH, C1-C6-alkoxy, C1-C6-alkoxycarbonyl, aromatic heterocyclyl, aryl and -S(O) n Group substitution of R2;

[0021] R4 and R5 independently represent H, -OH, C1-C 12 -alkyl, C1-C3-alkoxy, C1-C6-alkoxy-C1-C3-alkyl, C1-C6-alkoxycarbonyl-C1-C6-alkyl, N(C1-C3 alkyl)2 or -S(O) n R2,

[0022] or

[0023] R4 and R5 together with the nitrogen atom to which they are attached form a saturated or partially unsaturated or fully unsaturated five-membered, six-membered or seven-membered ring which, in addition to the nitrogen atom, may contain r carbon atoms, o oxygen atoms and may be optionally substituted by m4 groups selected from halogen, C1-C6 alkyl, halo-C1-C6 alkyl, oxo, -CO2R6;

[0024] R6 represents H,

[0025] or

[0026] represents C1-C8-alkyl, C3-C6-cycloalkyl, C3-C8-alkenyl or C3-C8-alkynyl, each of which is optionally substituted by m5 groups selected from halogen, -CN and C1-C2-alkoxy;

[0027] When Z is selected from Z-1 to Z-4, wherein Z-1 to Z-4 have the following meanings:

[0028] Then X3 represents H, F, Cl, Br or I,

[0029] X1 and X2 each independently represent H, F, Cl, Br, I, -OH, -CN, -NO2, -S(O) n R2 or -CO2R6,

[0030] or

[0031] 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;

[0032] When Z is selected from Z-5 to Z-7, wherein Z-5 to Z-7 have the following meanings:

[0033] Then X3 represents H or F,

[0034] X1 represents F, Cl, Br, I, -CH3, -CN, -NO2, -S(O) n R2 or -OS(O) n R2,

[0035] X2 represents -CF3, -CF2H, -OCF3, -OCF2H or -OCFH2;

[0036] R2 represents C1-C4-alkyl or C3-C4-cycloalkyl, each of which is substituted by m2 groups selected from F and Cl;

[0037] wherein the arrows respectively represent the bonds toward the group CO-G of formula (I);

[0038] m1 is 0, 1, 2, or 3;

[0039] m2 is 0, 1, 2, or 3;

[0040] m3 is 0, 1, 2, 3, 4, 5, 6, 7 or 8;

[0041] m4 is 0, 1, 2, 3, 4, or 5;

[0042] m5 is 0, 1, 2, 3, 4 or 5;

[0043] m6 is 0, 1, 2, or 3;

[0044] n is 0, 1, or 2;

[0045] o is 0, 1, or 2;

[0046] r is 3, 4, 5 or 6.

[0047] Preferably, wherein:

[0048] R1 represents C1-C3-alkyl, C3-C4-cycloalkyl, C2-C3-alkenyl, C2-C3-alkynyl or C1-C3-alkoxy, each of which is substituted by m1 groups selected from the group consisting of halogen, -CN, -OH and C1-C2-alkoxy;

[0049] G represents -OR3 or -NR4R5;

[0050] R3 represents H,

[0051] or

[0052] Represents 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 heterocyclyl, C1-C3-alkyl-aromatic heterocyclyl or C2-C6-alkynyl, each of which is substituted by m3 groups selected from the group consisting of F, Cl, Br, I, -CN, -OH, -S(O) n R2, C1-C4-alkoxy, aryl and aromatic heterocyclic groups;

[0053] R4, R5 independently represent H, -OH, C1-C6-alkyl, C1-C3-alkoxy, C1-C3-alkoxy-C1-C3-alkyl or -S(O) n R2, or

[0054] R4 and R5 together with the nitrogen atom to which they are attached form a saturated or partially unsaturated or fully unsaturated five-membered or six-membered ring which, in addition to the nitrogen atom, may also contain r carbon atoms, o oxygen atoms and may be optionally substituted by m4 groups selected from halogen, C1-C6-alkyl, halogen-C1-C6-alkyl, oxo, -CO2R6;

[0055] R2 represents a C1-C4-alkyl group;

[0056] R6 represents H,

[0057] or

[0058] represents C1-C6-alkyl, C3-C6-cycloalkyl, C3-C8-alkenyl or C3-C8-alkynyl, each of which is optionally substituted by m5 groups selected from halogen, -CN and C1-C2-alkoxy;

[0059] m1 is 0, 1, 2, or 3;

[0060] m3 is 0, 1, 2, 3, 4, 5, 6, 7 or 8;

[0061] m4 is 0, 1, 2, 3, or 4;

[0062] m5 is 0, 1, 2, or 3;

[0063] n is 0, 1, or 2;

[0064] o is 0, 1, or 2;

[0065] r is 3, 4 or 5.

[0066] More preferably,

[0067] in,

[0068] R1 represents C1-C3-alkyl, C2-C3-alkenyl, C2-C3-alkynyl or C1-C3-alkoxy, each of which is substituted by m1 groups selected from F, Cl and Br;

[0069] G represents -OR3 or -NR4R5;

[0070] R3 represents H,

[0071] or

[0072] 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 heterocyclyl, C1-C3-alkyl-aromatic heterocyclyl, phenyl-C1-C3-alkyl or aromatic heterocyclyl-C1-C3-alkyl, each of which is substituted by m3 groups selected from the group consisting of F, Cl, Br, I, -CN, -OH, -OCH3 or -S(O) n R2;

[0073] R4, R5 independently represent H, -OH, C1-C6-alkyl, C1-C3-alkoxy or -S(O) n R2;

[0074] or

[0075] R4 and R5 together with the nitrogen atom to which they are attached form a saturated five-membered or six-membered ring which contains 4 or 5 carbon atoms in addition to the nitrogen atom;

[0076] R2 represents a C1-C3-alkyl group;

[0077] m1 is 0, 1, 2, or 3;

[0078] m3 is 0, 1, 2, 3, 4, 5, 6, 7 or 8;

[0079] n is 0, 1 or 2.

[0080] More preferably,

[0081] in,

[0082] R1 represents -CH3, -CH=CH2, -CF=CH2, -CF3, -CF2H, -CH2F, -CH2Cl, -CF2CH3 or -OCH3;

[0083] G represents -OR3 or -NR4R5;

[0084] R3 represents H,

[0085] or

[0086] 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)CH2OCH3, (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;

[0087] n is 0, 1, or 2;

[0088] or

[0089] R4, R5 independently represent H, -CH3, -CH2CH3, -OH, -OCH3, -OCH2CH3, -OCH(CH3)2 or -SO2CH3,

[0090] or

[0091] R4 and R5 together with the nitrogen atom to which they are attached form a saturated five-membered ring or six-membered ring which contains 4 or 5 carbon atoms in addition to the nitrogen atom.

[0092] More preferably,

[0093] in,

[0094] Z stands for Z-1;

[0095] X3 represents H or F;

[0096] X1 and X2 each independently represent H, F, Cl, Br or -CN,

[0097] or

[0098] represents C1-C3-alkyl or C1-C3-alkoxy, each of which is substituted by m6 groups selected from F, Cl and Br;

[0099] m6 is 0, 1, 2, or 3.

[0100] More preferably,

[0101] in,

[0102] Z stands for Z-1;

[0103] X3 represents H or F;

[0104] X1 and X2 each independently represent H, F, Cl, Br, -CH3, -CN, -OCH3, -CF3, -CF2H, -OCF3 or -OCF2H.

[0105] More preferably,

[0106] Z stands for Z-5 or Z-7;

[0107] X3 represents H;

[0108] X1 represents F, Cl or Br;

[0109] X2 represents -CF3, -CF2H, -OCF3 or -OCF2H.

[0110] In the definition of compounds of general formula (I) given above, the terms used are generally defined as follows:

[0111] Alkyl is a saturated, straight-chain or branched hydrocarbon radical having in each case the number of carbon atoms specified, for example C1-C6-alkyl, such as 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, 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.

[0112] Halogen-substituted alkyl refers to the following straight-chain or branched alkyl groups: in these groups, some or all of the hydrogen atoms can be replaced by halogen atoms, for example C1-C2-haloalkyl, 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-dichloro-2-fluoroethyl, 2,2,2-trichloroethyl, pentafluoroethyl and 1,1,1-trifluoroprop-2-yl.

[0113] Alkenyl is an unsaturated, straight-chain or branched hydrocarbon radical having the number of carbon atoms specified in each case and having one double bond at any position, for example C2-C6-alkenyl, such as ethenyl, 1-propenyl, 2-propenyl, 1-methylethenyl, 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 1-ethyl-2-methyl-1-propenyl, 1-ethyl-2-methyl-2-propenyl, 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.

[0114] Alkynyl is a straight-chain or branched hydrocarbon radical having the number of carbon atoms specified in each case and having one triple bond at any position, such as C2-C6-alkynyl, such as ethynyl, 1-propynyl, 2-propynyl (or propargyl), 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.

[0115] Cycloalkyl refers to a carbocyclic saturated ring system having preferably 3 to 8 ring carbon atoms, for example cyclopropyl, cyclobutyl, cyclopentyl or cyclohexyl. In the case of optionally substituted cycloalkyl, this includes ring systems having substituents, also including substituents having double bonds on the cycloalkyl, for example alkylene, such as methylene.

[0116] In the case of optionally substituted cycloalkyl, polycyclic aliphatic systems are also included, for example 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 (norbornyl), adamant-1-yl and adamant-2-yl.

[0117] In the case of substituted cycloalkyl, spirocycloaliphatic systems are also included, for example spiro[2.2]pent-1-yl, spiro[2.3]hex-1-yl and spiro[2.3]hex-4-yl, 3-spiro[2.3]hex-5-yl.

[0118] Cycloalkenyl refers to a carbocyclic, non-aromatic, partially unsaturated ring system having preferably 4 to 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 double bonds on the cycloalkenyl, for example, alkylene groups such as methylene. In the case of optionally substituted cycloalkenyl groups, the description of substituted cycloalkyl groups applies accordingly.

[0119] Alkoxy is a saturated, straight-chain or branched alkoxy radical having in each case the number of carbon atoms indicated, for example C1-C6-alkoxy, such as 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, hexyloxy, 1,1-dimethylpropoxy, 1,2-dimethylpropoxy 1-ethylbutoxy, 2-ethylbutoxy, 1,1,2-trimethylpropoxy, 1,2,2-trimethylpropoxy, 1-ethyl-1-methylpropoxy and 1-ethyl-2-methylpropoxy. Halogen-substituted alkoxy is understood to mean the following straight-chain or branched alkoxy radicals having in each case the indicated number of carbon atoms: in which some or all of the hydrogen atoms may be replaced by halogen atoms as described above, for example C1-C2-haloalkoxy, such as 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-dichloro-2-fluoroethoxy, 2,2,2-trichloroethoxy, pentafluoroethoxy and 1,1,1-trifluoroprop-2-oxy.

[0120] Aryl refers to phenyl which is optionally substituted by 0-5 groups selected from fluorine, chlorine, bromine, iodine, cyano, hydroxy, C1-C3-alkyl, C1-C3-alkoxy, C3-C4-cycloalkyl, C2-C3-alkenyl and C2-C3-alkynyl.

[0121] The term "halogen" refers to fluorine, chlorine, bromine or iodine. If the term is applied to a radical, "halogen" refers to a fluorine, chlorine, bromine or iodine atom.

[0122] Depending on the nature of the substituents and the mode of attachment, the compounds of formula (I) may exist as stereoisomers. For example, when one or more asymmetrically substituted carbon atoms and / or sulfoxides are present, enantiomers and diastereomers may occur. Stereoisomers may be obtained from the mixture obtained during the preparation process by conventional separation methods, such as chromatographic separation methods. Similarly, stereoisomers may be selectively prepared by stereoselective reactions using optically active starting materials and / or auxiliary agents.

[0123] The present invention also relates to all stereoisomers encompassed by formula (I) but not specifically defined, and mixtures thereof. However, for the sake of simplicity, reference will always be made hereinafter to compounds of formula (I), although this is to be understood as meaning not only the pure compounds but also, if appropriate, mixtures with varying amounts of isomeric compounds.

[0124] Depending on the nature of the substituents defined above, the compounds of formula (I) have acidic properties and can form salts and, if appropriate, inner salts, or adducts with inorganic or organic bases or with metal ions. If the compounds of formula (I) carry hydroxyl, carboxyl or other groups that induce acidity, these compounds can react with bases to form salts. Suitable bases are, for example, hydroxides, carbonates, bicarbonates of alkali metals and alkaline earth metals, in particular sodium, potassium, magnesium and calcium; as well as ammonia; primary, secondary and tertiary amines with C1-C4-alkyl groups; mono-, di- and tri-alkanolamines of C1-C4-alkanols; choline and choline chloride; as well as 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, a metal salt, in particular an alkali metal salt or an alkaline earth metal salt, in particular a sodium salt and a potassium salt; or an ammonium salt, an organic amine salt or a quaternary ammonium salt, for example a salt of a cation of the formula [NRR′R″R″′]+ (in which R to R′″ each independently represent an organic radical, in particular an alkyl, aryl, aralkyl or alkaryl radical). Also suitable are alkylsulfonium salts and alkylsulfoxonium salts, for example C1-C4-trialkylsulfonium salts and C1-C4-trialkylsulfoxonium salts.

[0125] The compound of formula (I) can form salt by adding a suitable inorganic acid or organic acid to the basic group; the inorganic acid is, for example, HCl, HBr, H2SO4, H3PO4 or HNO3, the organic acid is, for example, a carboxylic acid (for example, formic acid, acetic acid, propionic acid, oxalic acid, lactic acid or salicylic acid) or a sulfonic acid (for example, p-toluenesulfonic acid), and the basic group is, for example, amino, alkylamino, dialkylamino, piperidyl, morpholinyl or pyridyl. In this case, these salts comprise the conjugate base of the acid as an anion.

[0126] Suitable substituents present in deprotonated form (eg sulfonic acids or carboxylic acids) can form internal salts with groups which themselves can be protonated (eg amino groups).

[0127] If a radical is polysubstituted by radicals, this means that the radical is substituted by one or more identical or different radicals mentioned above.

[0128] In all formulae specified hereinafter, unless otherwise defined, substituents and symbols have the same meanings as described in formula (I). The arrow in the chemical formulae indicates the point of attachment to the rest of the molecule.

[0129] Preferred, particularly preferred and very particularly preferred definitions of the individual substituents are described below. Further substituents of the general formula (I) not specified below have the definitions given above.

[0130] Examples of compounds of the general formula (I) are shown below in tabular form. Table 1 below lists the substituents in formula (I) defined in general terms.

[0131] Table 1 Compounds of formula (I)

[0132] Table 1 Compounds of formula (I)

[0133] The compounds of the present invention can be prepared by various methods listed below:

[0134] Route 1:

[0135] In Scheme 1 and the following schemes, the definitions of the substituents are the same as above. The 1,3-dipolar cycloaddition of nitrile oxides with suitable dipolarophiles is described in, for example, the following reviews: 1,3-dipolar Cycloaddition Chemistry, ed. 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.

[0136] Compounds of the present invention substituted at the 4- and 5-positions of the isoxazoline ring system can also be prepared by 1,3-dipolar cycloaddition using suitable 1,2-disubstituted olefins as dipolarophiles. Typically, this reaction yields a mixture of diastereoisomers that can be separated by column chromatography. Optically active isoxazolines can be obtained by chiral HPLC of suitable precursors or final products, by enantioselective reactions (e.g., enzymatic esterification or amide cleavage), or by using chiral auxiliaries on dipolarophiles, as described by Olssen (J. Org. Chem. 1988, 53, 2468). Suitable substituted acrylamides can also be used to prepare the compounds of the present invention (Scheme 3). These can be obtained from the acrylic acid esters described in Scheme 2 after hydrolysis and amide formation.

[0137] Route 2:

[0138] One option for activating acrylic acid is a carbodiimide, such as EDCI (Chen, FMF; Benoiton, NL Synthesis 1979, 709). For the preparation of acrylamide, see US Pat. No. 2,521,902, JP 60112746, J. of Polymer Science 1979, 17(6), 1655. Appropriately substituted acrylamides can be reacted with α-chlorooxime compounds in a 1,3-cycloaddition reaction to give the compounds of the present invention (Scheme 3).

[0139] Route 3:

[0140] The conversion of the functional group R3 can be carried out either at the olefin stage or at the isoxazoline stage.

[0141] The compound of formula (I) and / or its salt that can be synthesized by the above-mentioned reaction can also be prepared in a parallel manner. In this case, it can be completed in a manual, semi-automatic or fully automatic manner. For example, the aftertreatment or purification of the reaction, product and / or intermediate can be automatically carried out. In a word, this should be understood as meaning the step of, for example, D.Tiebes in Combinatorial Chemistry-Synthesis, Analysis, Screening, Wiley, 1999, page 1 to 34.

[0142] The compounds of formula (I) (and / or their salts) of the present invention—hereinafter collectively referred to as "compounds of the present invention"—have excellent herbicidal activity against a broad spectrum of economically important monocotyledonous and dicotyledonous annual harmful plants. They effectively control a wide range of weeds, achieving excellent results even at low dosages, and are useful as herbicides. Therefore, the present invention also encompasses the use of the compounds of formula (I) for controlling weeds.

[0143] The present invention therefore relates to a method for controlling unwanted plants or for regulating plant growth, wherein one or more compounds according to the invention are applied to plants (e.g. harmful plants, such as monocotyledonous or dicotyledonous weeds or unwanted crop plants), seeds (e.g. grains, seeds or vegetative propagules, such as tubers or shoots with buds) or plant growth areas (e.g. cultivated areas). The compounds according to the invention can be applied before planting (if appropriate, also by introduction into the soil), before emergence or after emergence. The following examples of various representative monocotyledonous and dicotyledonous weed flora that are controlled by the compounds according to the invention serve only to illustrate the invention and do not limit it in any way.

[0144] Monocotyledonous harmful plant genera: Aegilops, Agropyron, Agrostis, Alopecurus, Apera, Avena, Brachiaria, Bromus, Cenchrus, Commelina, Cynodon, Cyperus, Dactyloctenium, Digitaria, Echinochloa, Eleocharis, Eleusine, Eragrostis, and Panicum Eriochloa, Festuca, Fimbristylis, Heteranthera, Imperata, Ischaemum, Leptochloa, Lolium, Monochoria, Panicum, Paspalum, Phalaris, Phleum, Poa, Rottboellia, Sagittaria, Scirpus, Setaria, and Sorghum.

[0145] 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, Matricaria, Mentha, Mercurialis, Mullugo, Myosotis, Papaver, Pharbitis, Plantago, Polygonum, Portulaca, Ranunculus, Raphanus, Rorippa, Rotala, Rumex, Sassafras These include: lsola, Senecio, Sesbania, Sida, Sinapis, Solanum, Sonchus, Sphenoclea, Stellaria, Taraxacum, Thlaspi, Trifolium, Urtica, Veronica, Viola, and Xanthium.

[0146] When the compounds of the present invention are applied to the soil before emergence, the growth of harmful plant seeds stops 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 the competition of weeds that are harmful to crop plants at a very early point in time and in a lasting manner.

[0147] When the compounds according to the invention are applied to green plant parts post-emergence, growth is arrested after treatment and the harmful plants remain in the growth phase at the time of application or die completely after a certain period of time, thus making it possible to eliminate the competition of weeds that are harmful to crop plants at an extremely early point in time and in a lasting manner.

[0148] The compounds according to the invention can be selective in crops of useful plants and can also be used as non-selective herbicides.

[0149] Therefore, the technical solution of the present invention also includes the use of the compound of general formula (I) for controlling weeds.

[0150] Furthermore, the compounds of the general formula (I) according to the present invention are also suitable for the drying up and / or defoliation of plants.

[0151] As mentioned above, the present invention provides a pesticide herbicide, which is composed of an active ingredient and excipients, wherein the active ingredient includes at least one of the aforementioned 3-phenylisoxazolin-5-carboxamide compounds.

[0152] Preferably, the active ingredient is contained in the pesticide herbicide in an amount of 0.1-99.9% by weight.

[0153] The present invention has no particular limitation on the specific types of adjuvants in the herbicide. For example, the adjuvants may be various surfactants, solvents, etc. commonly used in the field of herbicides.

[0154] The compounds of the present invention can be applied using conventional formulations, including wettable powders, emulsifiable concentrates, sprayable solutions, powders, or granules. Thus, the present invention also provides herbicidal compositions comprising compounds of formula (I). Compounds of formula (I) can be formulated in a variety of ways, depending on typical biological and / or chemical physical parameters. Suitable formulation options include wettable powders (WP), water-soluble powders (SP), water-soluble concentrates, emulsifiable concentrates (EC), emulsions such as oil-in-water dispersions and water-in-oil dispersions (EW), sprayable solutions, suspension concentrates (SC), dispersible oil suspensions (OD), suspensions with oil or water as diluents, solutions with miscible oils, powders (DP), capsule suspensions (CS), seeded compositions, granules for broadcasting and soil application, sprayable granules, coated 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 are described, for example, in Winnacker-Küchler, Chemical Technology, Vol. 7, C. Hauser Verlag Munich, 4th edition 1986; Wade van Valkenburg, "Pesticide Formulations", Marcel Dekker, NY, 1973; K. Martens, "Spray Drying" Handbook, 3rd edition 1979, G. Goodwin Ltd. London.

[0155] Necessary formulation auxiliaries, such as inert substances, surfactants, solvents and other additives are likewise known and are described in, for example, Watkins, Handbook of Powder Diluents, Pesticides and Carriers, 2nd ed., Darland Caldwell, NJ; Hvophen, An Introduction to Clay Colloid Chemistry, 2nd ed., J. Wiley and Sons, NY; C. Marsden, A Guide to Solvents, 2nd ed., Interscience, NY 1963; McCutcheon, Detergents and Emulsifiers Annual, MC Publishing Company, Ridgewood, NJ; Sisley and Wood, Encyclopedia of Surfactants, Chemical Publishing Company, NY 1964; Ethylene Oxide Adduct Surfactants, Wiss.

[0156] Verlagagesell. Stuttgart 1976; Winnacker-Küchler, Chemical Processes, Volume 7, C. Hauser Verlag Munich, 4th edition 1986.

[0157] Wettable powders are homogeneously dispersible in water and contain, in addition to the active substance, a diluent or inert substance, ionic and nonionic surfactants (wetting agents, dispersants), for example, polyethoxylated alkylphenols, polyethoxylated fatty alcohols, polyoxyethylated fatty amines, fatty alcohol polyglycol ether sulfates, alkylsulfonates, alkylphenylsulfonates, sodium lignosulfonate, sodium 2,2'-dinaphthomethane-6,6'-disulfonate, sodium dibutylnaphthalenesulfonate or sodium oleoylmethyltaurate. To prepare wettable powders, the herbicide active substance is finely ground, for example using conventional apparatus such as hammer mills, fan mills or jet mills, and the adjuvants are mixed in simultaneously or sequentially.

[0158] The concentrated emulsion is prepared by dissolving the active substance in an organic solvent such as butanol, cyclohexanone, dimethylformamide, xylene or a mixture of relatively high-boiling aromatic compounds or hydrocarbons or solvents, and adding one or more ionic and / or nonionic surfactants (emulsifiers). Examples of emulsifiers that can be used are calcium alkylarylsulfonates such as calcium dodecylbenzenesulfonate, or nonionic emulsifiers such as fatty acid polyglycol esters, alkylaryl polyglycol ethers, fatty alcohol polyglycol ethers, propylene oxide-ethylene oxide condensation products, alkyl polyethers, sorbitan esters such as sorbitan fatty acid esters, or polyoxyethylene sorbitan esters such as polyoxyethylene sorbitan fatty acid esters.

[0159] Powders are obtained by grinding the active substance with finely divided solid materials, such as talc, natural clays such as kaolin, bentonite and pyrophyllite, or diatomaceous earth. Suspensions in water or oil can be prepared, for example, by wet grinding using a commercially available bead mill, with or without the addition of a surfactant of the type described above for the other formulations.

[0160] Emulsions such as oil-in-water emulsions (EW) can be prepared using aqueous organic solvents using stirrers, colloid mills and / or static mixers and, if desired, adding surfactants of another formulation type as described above.

[0161] Granules can be prepared by spraying the active substance onto an adsorbent and granulating with an inert material, or by concentrating the active substance onto the surface of a carrier such as sand or kaolinite and granulating the inert material with a binder such as polyvinyl alcohol, sodium polyacrylate, or mineral oil. Suitable active substances can be granulated using methods for preparing fertilizer granules and, if desired, mixed with fertilizers. 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 in the absence of solid inert materials.

[0162] For the preparation of granules using a mill, fluidized bed, extruder, and spraying, see, for example, the following processes: "Spray Drying Handbook," 3rd ed. 1979, G. Goodwin Ltd., London; J. E. Browning, "Agglomeration," Chemistry and Engineering, 1967, pp. 147ff; "Perry's Chemical Engineer's Handbook," 5th ed., McGraw-Hill, New York, 1973, pp. 8-57. For the formulation of crop protection products, see, for example, G. C. Lingman, "Weed Control as a Science," John Wiley & Sons, New York, 1961, pp. 81-96 and J. D. Frieder, S. A. Evans, "Handbook of Weed Control," 5th ed., Blackwell Scientific Research, Oxford, 1968, pp. 101-103.

[0163] Agrochemical formulations usually contain 0.1 to 99% by weight, in particular 0.1 to 95% by weight, of the active substance of formula (I). The concentration of the active substance 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 the active substance in concentrated emulsions can be about 1 to 90% by weight, preferably 5 to 80%. Powder formulations contain 1 to 30% by weight of active substance, usually preferably 5 to 20% by weight of active substance, whereas sprayable solutions contain about 0.05 to 80% by weight, preferably 2 to 50% by weight of active substance. As for the content of the active substance in water-suspended granules, it mainly depends on whether the active substance is liquid or solid, and the adjuvants, fillers, etc. used during granulation. The content of the active substance in water-suspended granules is, for example, between 1 and 95% by weight, preferably between 10 and 80% by weight.

[0164] The active substance formulations may additionally include tackifiers, wetting agents, dispersants, emulsifiers, penetrants, preservatives, antifreeze agents, solvents, fillers, carriers, colorants, antifoams, evaporation inhibitors and, generally, pH and viscosity regulators which are customary in each case.

[0165] Based on these formulations, it is also possible to mix with other pesticide active substances such as insecticides, acaricides, herbicides and fungicides, as well as with safeners, fertilizers and / or plant growth regulators, either as premixes or as canned mixes.

[0166] For application, commercially available formulations are diluted, if appropriate, in a customary manner, for example with water in the case of wettable powders, emulsifiable concentrates, dispersions and water-dispersible granules. Dusting formulations, granules for soil application or granules for broadcasting and sprayable solutions are usually not diluted further with other inert substances before application.

[0167] The required application rate of the compound of formula (I) varies depending on the ambient conditions, including, in particular, temperature, humidity and the type of herbicide used. The application rate may vary within a wide range, for example from 0.001 to 1.0 kg / ha or more of active substance, but preferably from 0.005 to 750 g / ha.

[0168] A carrier is an organic or inorganic substance, natural or synthetic, with which the active compound is mixed or bound for better application, in particular to plants or plant parts or seeds. The carrier, which can be solid or liquid, is generally inert and should be suitable for agricultural use.

[0169] Useful solid or liquid carriers include, for example, ammonium salts and natural rock dusts, such as kaolin, clay, talc, chalk, quartz, attapulgite, montmorillonite or diatomaceous earth; and synthetic rock dusts, such as finely divided silica, alumina and natural or synthetic silicates, resins, waxes, solid fertilizers; water; alcohols, especially butanol; organic solvents, mineral oils and vegetable oils, and their derivatives. Mixtures of the aforementioned carriers can also be used. Useful solid carriers for granules include, for example, crushed and fractionated natural rocks, such as calcite, marble, pumice, sepiolite, dolomite; and synthetic particles of inorganic and organic powders; as well as particles of organic materials, such as sawdust, coconut shells, corn cobs and tobacco stalks.

[0170] Suitable liquefied gas extenders or carriers are liquids which are gaseous at standard temperature and atmospheric pressure, for example aerosol propellants, such as halogenated hydrocarbons, or butane, propane, nitrogen and carbon dioxide.

[0171] In the formulation, viscosity-increasing agents such as carboxymethylcellulose, natural and synthetic polymers in the form of powders, granules or latexes, such as gum arabic, polyvinyl alcohol and polyvinyl acetate, or natural phospholipids such as cephalin and lecithin, as well as synthetic phospholipids can be used. Other additives may be mineral oils and vegetable oils.

[0172] If the extender used is water, organic solvents, for example, can also be used as auxiliary solvents. Suitable liquid solvents are, inter alia: aromatic compounds, such as xylene, toluene or alkylnaphthalenes; chlorinated aromatic compounds and chlorinated aliphatic hydrocarbons, such as chlorobenzene, vinyl chloride or methylene chloride; aliphatic hydrocarbons, such as cyclohexane or paraffins, such as mineral oil fractions, mineral oils 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; strongly polar solvents, such as dimethylformamide and dimethyl sulfoxide; and water.

[0173] The composition of the present invention may also contain other components, such as surfactants. Useful surfactants are emulsifiers and / or foaming agents, dispersants or wetting agents with ionic or nonionic properties, or mixtures of these surfactants. Examples of these are polyacrylates; lignin sulfonates; salts of phenolsulfonic acid or naphthalenesulfonic acid; polycondensates 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 taurates); phosphoric acid esters of polyethoxylated alcohols or phenols; fatty acid esters of polyols; and derivatives of compounds containing sulfate, sulfonate and phosphate groups, such as alkylaryl polyglycol ethers, alkylsulfonates, alkyl sulfates, arylsulfonates, protein hydrolysates, sulfite pulp waste liquors and methylcellulose. If one of the active compounds and / or one of the inert carriers is insoluble in water and the application is carried out in water, the presence of a surfactant is necessary. The proportion of surfactant is 5 to 40% by weight of the composition of the present invention. Dyes such as inorganic pigments, such as iron oxide, titanium oxide and Prussian blue, and organic dyes, such as alizarin dyes, azo dyes and metal phthalocyanine dyes, and trace nutrients, such as iron salts, manganese salts, boron salts, copper salts, cobalt salts, molybdenum salts and zinc salts can be used.

[0174] If appropriate, other additional components may also be present, such as protective colloids, binders, adhesives, thickeners, thixotropic substances, penetrants, stabilizers, chelating agents, 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 and more preferably 0.5 to 90% by weight of the active compound, most preferably 10 to 70% by weight. The active compounds or compositions according to the invention can be used as such or, depending on their respective physical and / or chemical properties, in the form of their formulations or use forms prepared therefrom, such as aerosols, capsule suspensions, cold mist concentrates, warm mist 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, foams, pastes, pesticide coated seed, suspension concentrates, suspoemulsion 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 products and synthetic substances impregnated with the active compounds, and microcapsules in polymeric substances and seed coating materials, and ULV cold mist and warm mist formulations.

[0175] The formulations can be prepared in a manner known per se, for example by mixing the active compound with at least one customary extender, solvent or diluent, emulsifier, dispersant and / or binder or fixative, wetting agent, water repellent, optionally drying agent and UV stabilizer, and optionally dyes and pigments, defoamers, preservatives, secondary thickeners, tackifiers, gibberellins and other processing aids.

[0176] The compositions according to the invention include not only preparations which are ready for use and can be applied to plants or seeds using suitable equipment, but also commercial concentrates which have to be diluted with water before use.

[0177] The active compounds according to the invention can be present as such, in their (commercial standard) formulations or in the use forms prepared from these formulations as a mixture with other (known) active compounds, such as insecticides, attractants, antiproliferatives, bactericides, acaricides, nematicides, fungicides, growth regulators, herbicides, fertilizers, safeners or semiochemicals.

[0178] The treatment of plants and plant parts with the active compounds or compositions according to the invention is carried out directly or by acting on their environment, habitat or storage space using customary treatment methods, for example by dipping, spraying, atomizing, irrigating, evaporating, dusting, fogging, broadcasting, foaming, spreading, spreading, watering (drenching), drip irrigation and, in the case of propagation material, in particular seeds, also as dry seed treatment with dusts, seed treatment with solutions, slurry treatment with water-soluble powders, by encrustation, by application of one or more coatings, etc. The active compounds can also be applied by the ultra-low volume method or by injecting the active compound preparation or the active compound itself into the soil.

[0179] In order to enhance the control effect of the 3-phenylisoxazoline-5-carboxamide compounds of the present invention and expand their scope of use, the 3-phenylisoxazoline-5-carboxamide compounds of the present invention can be used alone or in combination with other commonly used herbicides. There is no particular limitation on the proportion of the combined use and the proportion can be selected according to the conventional proportions used in the art, as long as the control effect after compounding can be enhanced, the scope of use can be expanded, and the safety can be improved.

[0180] In mixed formulations or tank-mixed formulations, suitable active substances that can be mixed with the active substance of the present invention are, for example, known substances described in "World New Pesticide Variety Technology Encyclopedia", China Agricultural Science and Technology Press, September 2010, and the literature cited therein. For example, the following herbicide active substances can be mixed with the mixture of formula (I), (Note: the name of the compound is either the common name according to the International Organization for Standardization (ISO) or the chemical name, with a code number when appropriate): acetochlor, butachlor, alachlor, isopropylamine, isopropylamine, s-isopropylamine, pretilachlor, acetochlor, acetochlor, naphthiachlor, R-(l-)naphthiachlor, propanil, mefenacet, bisbenzamide, fluazifop, dimethoate, flufenacet, bromomethoate, dimethoate, high-efficiency dimethoate, ethoxymethoate, flufenacet, methoxymethoate, metazachlor, isopropylamine, high-efficiency methyl ester, high-efficiency propyl ester , dipropylene glycol, pethoxachlor, butyrac, cyproconazole, flumethalin, heptamiprole, isobutachlor, propargyl chloramine, terbutachlor, dimethylaminopropylamine, dimethoate, chlorfenapyr, trimethylcyclohexane, chlorfenapyr, propyracyl chloramine, valeryl chloramine, carbamyl, new Yanling, tricyclic chlorfenapyr, butenesulfonamide, butenesulfonamide, mesotrione, benzylchlor, quinone, benzylchlor, naphthamide, acetoacetamide, naphthamide, thiazolin, cypermethrin, benzylchlor, benzylchlor, cypermethrin, benzylchlor, cypermethrin, atrazine, simazine, promethazine, cyanamide, simethazine, ametryn, propazine, isopropyl chloramine, fluazifop, terbutylamine, terbutylazine, triazine fluazifop, cyprodinil, gamphozone, grass Jin, Promethazine, Simatolin, Azide, Dichlorvos, Isopentyl, Cyclopropane, Metazine, Another Butylazine, Second Butylton, Terbutalone, Methoxypropyl, Cyanamide, Cyanocyanine, Kolazone, Atrazine, Metazine, Licorice, Cyanuric acid, Indaziflam, Chlorsulfuron, Metsulfuron-methyl, Bensulfuron-methyl, Chlorimsulfuron-methyl, Bensulfuron-methyl, Thisulfuron-methyl, Pyrazosulfuron-methyl, Metsulfuron-methyl, Iodosulfuron-methyl sodium salt, Formamidosulfuron-methyl, Ethylsulfuron-methyl, Bensulfuron-methyl, Metsulfuron-methyl, Nicosulfuron, Ethamidosulfuron-methyl, Acesulfuron-methyl, Ethoxysulfuron-methyl, Cyprosulfuron-methyl, Sulfonsulfuron-methyl, Tetrazosulfuron, Fentazuron-methyl, Monosulfuron-methyl, Monosulfuron, Fluazuron-methyl, Flupyrazosulfuron-methyl, Epoxysulfuron Sulfur-methyl, azole pyrazosulfuron, primisulfuron, propensulfuron-methyl, trifloxysulfuron, sulfosulfuron, trifloxysulfuron, trifloxysulfuron, metsulfuron-methyl sodium, primisulfuron, methylthiosulfuron, pyrimidisulfon-methyl, Propyrisulfuron (propyrisulfuron), pyrazosulfuron-methyl, acifluorfen, fomesafen, lactofen, fluazifop-butyl, oxyfluorfen, oxazolidinone, benfibrate, chlorpyrifos ethyl, methylcarboxylic acid butyl, trifluoroacetic acid butyl, methoxy-nitropropane, trifluosuccinate, fluorinated herbicide ether, flutosulfuron, nitropropane, methylpyralid, dimethoate, flutosulfuron, flutosulfuron ester, Halosafen, chlorotoluron, isoproturon, linuron, diuron,Saproron, Fluorouron, Benthiocarb, Methylbenthiocarb, Benthiocarb, Sulfathiocarb, Isoxuron, Terbuthiuron, Clodinuron, Chlorbromon, Methylthiocarb, Acyril, Methoxythiocarb, Bromothiocarb, Methoxythiocarb, Chlorthiocarb, Monisouron, Cyclothiocarb, Fenuron, Flusulfuron, Cyclothiocarb, Cyclothiocarb, Cyclothiocarb, Cyclothiocarb, Thiofuron, Buthiuron, Cyclothiocarb, Parafluron, Methiathiazolin, Lomthiocarb, Trimethylisourea, Oxazol, Monisouron, Anisuron, Methiuron, Chloreturon, Tetrafluron, Betaine, Betaine-ethyl Ester, Betaine, Sulfathiocarb, Terbuthiuron, Avena Cinnamomum, Anipropyrin, Chlorprophion, Diclofenac, Anipropyrin, Chlorpheniramine, Carboxazo le, Chlorprocarb, Fenasulam, BCPC, CPPC, Carbasulam, Butylcarb, Fenasulam ... 2-Methyl-4-chlorobutyric acid, 2,4,5-T, 2,4,5-T propionic acid, 2,4,5-T butyric acid, 2-Methyl-4-chloroamine salt, Mediben, Cypermethrin, Fenpyraclostrobin ... in, propanol, glyphosate, safflower, glufosinate, methylamine glufosinate, glufosinate sulfide, piperphosphine, bialaphos, disulfide, glufosinate, vine glufosinate, valoron, dimethylamino glufosinate, oxalophos, imazapyr, imazapyr, imazapyr, imazapyr, imazapyr ammonium, imazapyr, imazapyr, cloflupyr, cloflupyr 2-ethylhexyl ester, clopyralid, amiloride, triclopyr, dithiopyr, halofop, triclopyralid, thiopyralid, flupyralid, chlorpyrifos, flupyralid, chlorpyrifos, flupyralid, flupyralid, triclopyralid butoxyethyl ester, Cliodinate, sethoxydim, clethodim, cycloxydim, chlorpyrifos, cyclohexanone, butoxydim, oxaclofop, pyraclofop, Buthidazole, metribuzin,Hexazinone, Metamitron, Ethylmetazolin, Ametridione, Amibuzin, Bromoxynil, Octanoyl Bromoxynil, Octanoyl Ioxyl, Ioxyl, Dichlobenil, Diphenylacetonitrile, Dipyridoxal, Hydroxypyridoxal, Iodobonil, Sulfursulfuron, Difluorosulfuron, Penoxsulam, Sulfursulfuron, Chlorosulfuron, Dichlorosulfuron, Pyroxypyramide, Fluorosulfuron, Bispyribac-butyl, Cyclopyramide, Pyroxypyramide, Pyroxypyramide, Bispyribac-butyl, Cyclopyramide, Pyroxypyramide, Bispyribac-butyl, Mesotrione, Sulcotrione, Tembotrione, Tefuryltrione, Bicyclopyrone, Ketodpiradox, Isoxaflutole, Isoxachlorpyrifos, Fenoxasulfone, M Ethiozolin, isopropylpyraclostrobin, pyrasulfobutyl, pyrazoline, wild yanquat, benzylpyrachlor, pyrazoline, pyrasulfotole, benzylpyrazone, pyroxasulfone, pyrazoline, fluazifop, chlorfenapyr, amine pyraclostrobin, pyrazoline, fluazifop, sulfentrazone, Bencarbazone, bispyribac, fluazifop-butyl, bromocriptine, isothiocyanate, cypermethrin, cypermethrin, terclopyralid, Flupropacil, indolone, flumethoxal, fluazifop-butyl, cypermethrin, phthalein, Flumezin, pentachlorophenol (sodium), dinitrophenol, dinitrophenol, dinitrophenol, dioxin, dioxetone, oxadiazol, oxadiazol, cyclopentane Fluazifop, flumethoxam, fluazifop-butyl, tetrazolam, flupyridazone, herbicide-resistant, bromomyxin, dimethylpyridazone, pyridafol, quinclorac, quinmechlor, bentazon, pyridazone, oxaziclomefop, chlorpyrifos, isopropylpyridazone, cyproconazole, isopropylpyridazone, indole, sodium chlorate , dalapon, trichloroacetic acid, monochloroacetic acid, hexachloroacetone, tetrafluoropropionic acid, grass fast, bromophenol oxime, triazole sulfonate, methomyl, furochlor, furochlor, ethyl furochlor, chloranil, chlorthalid, fluchloralidone, barnyard grass, acrolein, benzylpyridinium chloride, benzylpyridinium chloride, avena sativa ester, thiadiazole, cotton amine, hydroxythiocarb, methoxybenzone, benzylpyridinium chloride, chloranil, trichloropropionic acid, Al orac, Diethamquat, Etnipromid, Iprymidam, Ipfencarbazone, Thiencarbazone-methyl, Pyrimisulfan, Chlorflurazole, Tripropindan, Sulglycapin, Methylsulfuron, Cambendichlor, Cyprodinil, Thiencarbazone, Fenthiocyanate ...D489, LS 82-556, KPP-300, NC-324, NC-330, KH-218, DPX-N8189, SC-0744, DOWCO535, DK-8910, V-53482, PP-600, MBH-001, KIH-9201, ET-751, KIH-6127, and KIH-2023. These components can be used alone or in combination of two or more, and the ratio in the case of mixing can be freely selected.

[0181] Examples of safeners include benoxacor, BPCMS (BPCMS, CSB), cloquintocet, cloquintocet-mexyl, cumyluron, cyometrinil, cyprosulfamide, daimuron (dymron), dichlormid, dicyclonon (diclonon), dietholate, dimepiperate, disulphoton, fenpyroxil, and fenpyroxil. chlorazole), fenchlorazole-ethyl, fenclorim, flurazole, fluxofenim, furilazole, isoxadifen, isoxadifen-ethyl, MCPA, mecoprop, mefenpyr, mefenpyr-diethyl, mephenate, methoxyphenone, 1,8-naphthalic anhydride anhydride, NA), octamethylene-diamine, oxabetrinil, hexim, 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-azaspiro[4,5]decane-4-carbodithioate (MG838), (3-dichloroacetyl-5-(2-furyl)-2,2-dimethyloxazolidine) (MON13900), (N-allyl-N-[(1,3-dioxolan-2-yl)methyl]dichloroacetamide (PPG-1292), 3-(dichloroacetyl)-2,2-dimethyl-1,3-oxazolidine (R28725), 3-(dichloroacetyl)-2,2,5-trimethyl-1,3-oxazolidine (R29148) and 1-dichloroacetylazepane (TI-35), etc.These components may be used alone or in combination of two or more. When mixed, the ratio between them can be freely selected.

[0182] As described below, it is also particularly important to treat transgenic seeds with the active compounds or compositions of the present invention. This relates to seeds of plants containing at least one heterologous gene that is 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. Such heterologous genes are preferably derived from Bacillus, in which case the gene product is effective against European corn borer and / or western corn rootworm. More preferably, the heterologous gene is derived from Bacillus thuringiensis.

[0183] In the context of the present invention, the composition of the present invention is applied to the seed alone or in a suitable formulation. Preferably, the seed is treated in a sufficiently stable state so that no damage occurs during the treatment process. Generally, the seed can be treated at any time between harvesting and sowing. Generally, seeds are used that have been separated from the plant and the cobs, shells, stems, husks, hairs or pulp have been removed. 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 treated with water after drying and then dried can also be used.

[0184] When treating seed, it is generally necessary to ensure that the amount of the composition according to the invention and / or other additives applied to the seed is selected so that germination of the seed and the resulting plant are not impaired. This must be ensured in particular in the case of active compounds that can have phytotoxic effects at certain application rates.

[0185] The composition of the present invention can be applied directly, i.e., without any other components and without dilution. Generally, the composition is preferably applied to the seed in a suitable formulation. Suitable formulations and methods for seed treatment are known to those skilled in the art and are described in, for example, US 4,272,417A, US 4,245,432A, US 4,808,430, US 5,876,739, US 2003 / 0176428A1, WO 2002 / 080675A1, and WO 2002 / 028186A2.

[0186] The active compounds which can be used according to the invention can be converted into customary seed dressing formulations, such as solutions, emulsions, suspensions, powders, foams, slurries or other seed coating compositions, and also ULV formulations.

[0187] These formulations are prepared in a known manner by mixing the active compounds with conventional additives, such as conventional extenders and also solvents or diluents, dyes, wetting agents, dispersants, emulsifiers, defoamers, preservatives, secondary thickeners, adhesives, gibberellins and water. Dyes which may be present in the seed dressing formulations which can be used according to the invention are all dyes customary for such purposes.

[0188] Pigments that are sparingly soluble in water or dyes that are soluble in water may be used. Examples include dyes known under the names Rhodamine B, CI Pigment Red, and CI Solvent Red 1.

[0189] Useful wetting agents that may be present in the seed dressing formulations which can be used according to the invention are all substances which promote wetting and are customary for formulating agrochemically active compounds. Alkyl naphthalenesulfonates, such as diisopropyl naphthalenesulfonate or diisobutyl naphthalenesulfonate, can preferably be used.

[0190] Suitable dispersants and / or emulsifiers that may be present in the seed dressing formulations that can be used according to the invention are all nonionic, anionic, and cationic dispersants commonly used for formulating agrochemical active compounds. Preference is given to using nonionic or anionic dispersants, or mixtures of nonionic or anionic dispersants. Suitable nonionic dispersants include, in particular, ethylene oxide / propylene oxide block polymers, alkylphenol polyglycol ethers, and tristyrylphenol polyglycol ethers, and their phosphated or sulfated derivatives. Suitable anionic dispersants are, in particular, ligninsulfonates, polyacrylates, and arylsulfonate-formaldehyde condensates.

[0191] Antifoams which may be present in the seed dressing formulations which can be used according to the invention are all foam-inhibiting substances which are customary for formulating agrochemical active compounds. Silicone antifoams and magnesium stearate can preferably be used.

[0192] Preservatives that may be present in the seed dressing formulations which can be used according to the invention are all substances which can be used for such purposes in agrochemical compositions. Examples include dichlorophen and benzyl alcohol hemiformal.

[0193] Secondary thickeners which may be present in the seed dressing formulations which can be used according to the invention are all substances which can be used for such purposes in agrochemical compositions. Preferred examples include cellulose derivatives, acrylic acid derivatives, xanthan gum, modified clays and finely divided silica.

[0194] Useful adhesives that may be present in the seed dressing formulations which can be used according to the invention are all customary binders which can be used in seed dressing products. Preferred examples include polyvinyl pyrrolidone, polyvinyl acetate, polyvinyl alcohol and methylcellulose (tylose).

[0195] The seed dressing formulations that can be used according to the invention can be used to treat various types of seeds (including seeds of transgenic plants) directly or after being diluted with water in advance. In this case, additional synergistic effects will also occur in the interaction with the substances formed by expression.

[0196] Useful equipment for treating seeds with the seed dressing formulations that can be used according to the invention or with formulations prepared therefrom by adding water is any mixing apparatus conventionally used for seed dressing. Specifically, the seed dressing process involves placing the seeds in a mixer, adding the desired amount of the seed dressing formulation (either as such or after prior dilution with water), and mixing until the formulation is evenly distributed over the seeds. If appropriate, this is followed by a drying operation.

[0197] Since the active compounds according to the invention have good phytocompatibility, good homeothermic animal toxicity and good environmental compatibility, they are suitable for protecting plants and plant organs, increasing harvest yields and improving the quality of harvested crops.

[0198] They can preferably be used as crop protection agents. They are active against normally sensitive and resistant species and against all or specific development stages.

[0199] Plants that can be treated according to the invention include the following major crop plants: corn, soybean, cotton, Brassica oilseeds, such as Brassica napus (e.g., canola), Brassica rapa, B. juncea (e.g., (wild) mustard) and Brassica carinata, rice, wheat, sugar beet, sugar cane, oats, rye, barley, millet and sorghum, triticale, flax, vines and various fruits and vegetables of various plant taxa, such as Rosaceae sp. (e.g., pome fruits such as apples and pears, and stone fruits such as apricots, cherries, almonds and peaches, berries such as strawberries), Ribesioidae sp., Juglandaceae sp., Betulaceae sp., Anacardiaceae sp., Fagaceae sp. sp.), Moraceae sp., Oleaceae sp., Actinidaceae sp., Lauraceae sp., Musaceae sp. (e.g., banana trees and plantains), Rubiaceae sp. (e.g., coffee), Theaceae sp., Sterculiceae sp., Rutaceae sp. (e.g., lemons, oranges, and grapefruits), Solanaceae sp. (e.g., tomatoes, potatoes, peppers, eggplant), Liliaceae sp., Compositiae sp. (e.g., lettuce, artichoke, and chicory, including root chicory, endive, or common chicory), chicory), Umbelliferae sp. (e.g., carrots, parsley, celery, and celeriac), Cucurbitaceae sp. (e.g., cucumbers (including gherkins), pumpkins, watermelons, calabashes, and melons), Alliaceae sp. (e.g., onions and leeks), Cruciferae sp.(e.g. white cabbage, red cabbage, broccoli, cauliflower, Brussels sprout, pak choi, kohlrabi, radish, horseradish, cress, Chinese cabbage), Leguminosae sp. (e.g. peanuts, peas and beans, such as sword and broad beans), Chenopodiaceae sp. (e.g. Swiss chard, fodder beets, spinach, beetroot), Malvaceae (e.g. okra), Asparagaceae (e.g. asparagus); useful and ornamental plants for horticulture and forestry; and in each case genetically modified forms of these plants.

[0200] As mentioned above, all plants and their parts can be processed according to the present invention. In a preferred embodiment, wild plant species and plant cultivars, or those obtained by conventional biological breeding methods such as hybridization or protoplast fusion, and their parts are processed. In another preferred embodiment, transgenic plants and plant cultivars (genetically modified organisms) and their parts obtained by genetic engineering methods, if appropriate, in combination with conventional methods, are processed. The term "parts" or "parts of plants" or "plant parts" has been explained above. Particularly preferably, plants of each commercially available conventional plant cultivar or those plants currently being used are processed according to the present invention. Plant cultivars are understood to mean plants with new characteristics ("traits") grown by conventional breeding, by mutation or by recombinant DNA technology. They can be cultivars, variants, biotypes or genotypes.

[0201] The treatment method of the present invention can be used for processing genetically modified organisms (GMOs), such as plants or seeds.Genetically modified plants (or transgenic plants) are plants in which heterologous genes have been stably integrated into the genome.Term " heterologous gene " essentially means following gene: it provides or assembles in vitro, and when the gene is introduced into the nucleus, chloroplast or mitochondrial genome, it gives the transformed plant new or improved agronomy or other traits, because it expresses the protein or polypeptide of the concern or other genes present in the plant, or makes other genes present in the plant lower or silence (using, for example, antisense technology, co-suppression technology or RNAi-technology [RNA interference]).The heterologous gene in the genome is also referred to as transgenic.The transgenic defined according to its specific existence in the plant genome is referred to as conversion or transgenic strain.

[0202] Depending on the plant species or plant cultivars, their location and growth conditions (soil, climate, vegetation period, nutrition), the treatment according to the invention may also result in superadditive ("synergistic") effects. For example, the following effects may occur that exceed actual expectations: reduced application rates and / or broadened activity spectrum and / or increased efficacy of the active ingredients and compositions that can be used according to the 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 the harvested product, higher sugar concentration in the fruits, better storage stability and / or better processability of the harvested product.

[0203] Plants and plant cultivars which are preferably treated according to the invention include all plants which have genetic material which impart particularly advantageous, useful traits to these plants (whether obtained by breeding and / or biotechnological means).

[0204] Examples of nematode-resistant plants are described in U.S. patent applications such as 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.

[0205] The plant that can be processed according to the present invention is a hybrid plant that has expressed the characteristics of heterosis or hybrid effect, which usually causes higher yield, vigor, better health and resistance to biological and abiotic stress factors. The plant is usually obtained by hybridizing a selfing male sterile parent line (hybridization female parent) with another selfing male fertile parent line (hybridization male parent). Hybrid seeds are usually harvested from male sterile plants and sold to growers. Male sterile plants can sometimes (for example in corn) be produced by emasculation (i.e. mechanical removal of male reproductive organs or male flowers), but more generally, male sterility is produced by the genetic determinants in the plant genome. In this case, and particularly when seed is the desired product harvested from a hybrid plant, it is usually advantageous to ensure that the male fertility in the hybrid plant (which contains the genetic determinants responsible for male sterility) is fully restored. This can be achieved by ensuring that the hybrid parent has a suitable fertility restoration gene that can restore male fertility in the hybrid plant comprising the genetic determinants 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 by plant biotechnology methods (e.g., genetic engineering). WO 89 / 10396 describes a particularly useful method for obtaining male sterile plants, in which, for example, ribonucleases (e.g., barnacles) are selectively expressed in the tapetum cells in the stamens. Fertility can then be restored by expressing ribonuclease inhibitors (e.g., barnacles inhibitors) in the tapetum cells.

[0206] Plants or plant cultivars (obtained by plant biotechnology methods such as genetic engineering) which may be treated according to the invention are herbicide-tolerant plants, i.e. plants made tolerant to one or more given herbicides. These plants can be obtained by genetic transformation or by selection of plants containing mutations imparting such herbicide tolerance.

[0207] Herbicide-tolerant plants are, for example, glyphosate-tolerant plants, i.e., plants that are tolerant to the herbicide glyphosate or its salts. Plants can be made tolerant to glyphosate in various ways. Thus, 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 are 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 the petunia EPSPS (Shah et al., 1986, Science 233, 478-481), the gene encoding the tomato EPSPS (Gasser et al., 1988, J. Biol. Chem. 263, 4280-4289), or the gene encoding the Eleusine EPSPS (WO 01 / 66704). The EPSPS gene may also be a mutant EPSPS. Glyphosate-tolerant plants may also be obtained by expressing a gene encoding a glyphosate oxidoreductase. Glyphosate tolerant plants can also be obtained by expressing a gene encoding a glyphosate acetyltransferase. Glyphosate tolerant plants can also be obtained by selecting plants comprising naturally occurring mutants of the aforementioned genes. Plants expressing the EPSPS gene that confer glyphosate tolerance have been documented. Plants expressing other genes (e.g., decarboxylase genes) that confer glyphosate tolerance have been documented.

[0208] Other herbicide-resistant plants are, for example, plants that are tolerant to herbicides that inhibit glutamine synthetase (e.g., bialaphos, phosphinothricin, or glufosinate). These plants can be obtained by expressing enzymes that detoxify the herbicides or by expressing mutant glutamine synthetases that are resistant to inhibition. An example of such an effective detoxifying enzyme is an enzyme encoding phosphinothricin acetyltransferase (e.g., the bar or pat proteins of Streptomyces species). Plants expressing exogenous phosphinothricin acetyltransferase have been described.

[0209] Other herbicide-tolerant plants are plants that are tolerant to herbicides that inhibit hydroxyphenylpyruvate dioxygenase (HPPD). Hydroxyphenylpyruvate dioxygenase is an enzyme that catalyzes the reaction of converting parahydroxyphenylpyruvate (HPP) into homogentisate. Plants tolerant 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. Tolerance to HPPD inhibitors can also be achieved by transforming plants with genes encoding certain enzymes that can form homogentisate despite the inhibition of the natural HPPD enzyme by the HPPD inhibitor. Such plants are described in WO99 / 34008 and WO02 / 36787. In addition to using genes encoding HPPD-tolerant enzymes, plants can also be transformed with genes encoding prephenate dehydrogenase to improve their tolerance to HPPD inhibitors, as described in WO 2004 / 024928. In addition, plants can be made more tolerant to HPPD inhibitors by inserting genes encoding enzymes capable of metabolizing or degrading HPPD inhibitors (e.g., CYP450 enzymes) into the genome of the plant (see WO 2007 / 103567 and WO 2008 / 150473).

[0210] Other herbicide resistant plants are plants that have tolerance to acetolactate synthase (ALS) inhibitors. Known ALS inhibitors include, for example, sulfonylureas, imidazolinones, triazolopyrimidines, pyrimidinyloxy (thio) benzoates and / or sulfonylaminocarbonyltriazolinone herbicides. Different mutations in the known ALS enzyme (also referred to as acetohydroxy acid synthase, AHAS) confer tolerance to different herbicides and herbicide groups, as described in Tranel and Wright (Weed Science, 2002, 50, 700-712). The preparation of sulfonylurea tolerant plants and imidazolinone tolerant plants has been described. Other sulfonylurea tolerance and imidazolinone tolerant plants have also been described.

[0211] Other plants tolerant to imidazolinones and / or sulfonylureas can be obtained by induced mutations, by selection in cell cultures in the presence of the herbicide or by mutagenesis breeding (see, for example, US 5,084,082 for soybeans, WO 97 / 41218 for rice, US 5,773,702 and WO 99 / 057965 for sugar beet, US 5,198,599 for lettuce or WO 01 / 065922 for sunflower).

[0212] Plants or plant cultivars (obtained by plant biotechnology methods such as genetic engineering) which may also be treated according to the invention are tolerant to abiotic stress factors. Such plants can be obtained by genetic transformation or by selection of plants containing mutations imparting such stress resistance. Particularly useful stress-tolerant plants include the following:

[0213] a. A plant comprising a transgenic plant capable of reducing the expression and / or activity of a poly (adenosine diphosphate - ribose) polymerase (PARP) gene in a plant cell or plant;

[0214] b. plants comprising a stress tolerance enhancing transgenic plant capable of reducing the expression and / or activity of a PARG encoding gene in a plant or plant cell;

[0215] c. A plant containing a stress tolerance-enhancing transgene encoding a plant functional enzyme of the nicotinamide adenine dinucleotide salvage biosynthetic pathway, wherein the plant functional enzyme includes nicotinamidase, nicotinyl acid phosphoribosyltransferase, nicotinic acid mononucleotide adenylyltransferase, nicotinamide adenine dinucleotide synthetase or nicotinamide phosphoribosyltransferase.

[0216] Plants or plant cultivars (obtained by plant biotechnology methods such as genetic engineering) which may also be treated according to the invention show altered quantity, quality and / or storage stability of the harvested products and / or altered properties of specific components of the harvested products, are, for example:

[0217] 1) Transgenic plants which synthesize modified starch which has been modified with respect to its physicochemical properties compared to the synthesized starch in wild-type plant cells or plants, in particular with respect to the amylose content or the amylose / amylopectin ratio, the degree of branching, the average chain length, the side chain distribution, the viscosity behavior, the gel strength, the starch granule size and / or the starch granule morphology, thereby making it more suitable for specific applications.

[0218] 2) Transgenic plants that synthesize non-starch carbohydrate polymers or that synthesize non-starch carbohydrate polymers with altered properties compared to wild-type plants that have not been genetically modified. Examples are plants that produce polyfructose (especially of the inulin and fructan types); plants that produce α-1,4-glucans; plants that produce α-1,6-branched α-1,4-glucans; and plants that produce alternans.

[0219] 3) Transgenic plants that produce hyaluronic acid.

[0220] 4) Transgenic plants or hybrid plants, such as onions, with specific characteristics such as "high soluble solids content", "low irritation" (LP) and / or "long storability" (LS).

[0221] Plants or plant cultivars (obtained by plant biotechnology methods such as genetic engineering) which may also be treated according to the invention are plants, for example cotton plants, with altered fiber properties. These plants can be obtained by genetic transformation or by selection of plants containing a mutation imparting such altered fiber properties, including:

[0222] a) Plants, such as cotton plants, comprising an altered form of a cellulose synthase gene;

[0223] b) plants, such as cotton plants, comprising an altered form of an rsw2 or rsw3 homologous nucleic acid, such as a cotton plant with enhanced expression of sucrose phosphate synthase;

[0224] c) Plants, such as cotton plants, having increased expression of sucrose synthase;

[0225] d) Plants, such as cotton plants, having altered the timing of plasmodesmata gating at the base of fiber cells, for example by downregulating fiber-selective β-1,3-glucanase;

[0226] e) Plants, such as cotton plants, having reactively modified fibers, for example, by expressing N-acetylglucosamine transferase genes (including nodC) and chitin synthase genes.

[0227] Plants or plant cultivars (obtained by plant biotechnology methods such as genetic engineering) which may also be treated according to the invention are plants, for example oilseed rape or related Brassica plants, with altered oil profile characteristics. Such plants can be obtained by genetic transformation or by selection of plants containing a mutation imparting such altered oil properties and include:

[0228] a) Plants producing oil with a high oleic acid content, such as rapeseed plants;

[0229] b) plants producing oil with a low linolenic acid content, such as rapeseed plants;

[0230] c) Plants that produce oils with low levels of saturated fatty acids, such as oilseed rape plants.

[0231] Plants or plant cultivars (obtained by plant biotechnology methods such as genetic engineering) which may also be treated according to the invention are virus-resistant plants (e.g. resistant to potato virus Y) (the SY230 and SY233 lines from Tecnoplant, Argentina), such as potatoes, or plants made resistant to diseases such as potato late blight (e.g. the RB gene), or plants exhibiting reduced cold-induced sweetness (which carry the genes Nt-Inh, II-INV) or plants exhibiting a dwarf phenotype (A-20 oxidase gene).

[0232] Plants or plant cultivars (obtained by plant biotechnology methods such as genetic engineering) which may also be treated according to the invention are plants, for example oilseed rape or related Brassica plants, with altered seed shattering properties. Such plants can be obtained by genetic transformation or by selection of plants containing a mutation imparting such altered properties, and include plants, such as oilseed rape, with reduced or decreased seed shattering.

[0233] Particularly useful transgenic plants that can be treated according to the present invention are plants having a transformed strain or a combination of transformed strains that are the subject of a request for 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 regarding this can be obtained 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. As of the filing date of this application, a request having the following information has been approved or is pending approval by APHIS:

[0234] Petition: The identification number of the petition. Technical specifications for the transformed strains can be found in the specific petition document, which can be obtained from the APHIS website using the petition number. These specifications are incorporated herein by reference.

[0235] - Extension of Petition: Refers to a prior petition requesting an extension of scope or time limit.

[0236] - Institution: The name of the entity submitting the request.

[0237] -Regulated article: plant species involved.

[0238] - Transgenic phenotype: A trait conferred to a plant by transformation.

[0239] - Transformation event or line: The name of a single event or multiple events (sometimes also called a single event or multiple events) for which non-regulated status is required.

[0240] -APHIS Documents: Various documents published by APHIS that are relevant to the request or that are available from APHIS upon request.

[0241] Particularly useful transgenic plants which may be treated according to the invention are plants which contain transformation lines or combinations of transformation lines and which are listed, for example, in the databases of the regulatory agencies of 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).

[0242] When the active substances of the present invention are used on genetically modified crops, in addition to the harmful plant growth inhibitory effects observed on other crops, they often exhibit specific effects on the corresponding genetically modified crops, such as improved or expanded weed control, improved application rates, preferably a good combination of the resistance of the genetically modified crop and the performance of the herbicide, and effects on the growth and yield of the genetically modified crop plants. Therefore, the present invention also provides the use of the compounds as herbicides for controlling harmful plants in genetically modified crop plants.

[0243] Furthermore, the compounds of the present invention can significantly regulate the growth of crop plants. By modulating plant metabolism, these compounds can be used to control plant composition and promote harvest, for example by causing plant desiccation and dwarfing. Furthermore, they are suitable for regulating and inhibiting undesirable plant growth without disrupting crop growth. Inhibiting plant growth plays a very important role in many monocotyledonous and dicotyledonous crops because it can reduce or completely prevent lodging.

[0244] If there is a conflict between the nomenclature and the structural formula of the compound in the present invention, the structural formula shall prevail, unless the structural formula contains obvious errors.

[0245] Compared with the prior art, the compound of formula (I) provided by the present invention has better herbicidal activity and safety. DETAILED DESCRIPTION

[0246] The following examples are provided to illustrate the present invention and should not be construed as limiting the present invention in any way. The scope of the rights claimed by the present invention is set forth in the claims. Simple substitutions or modifications made by those skilled in the art to the present invention fall within the technical solutions protected by the present invention.

[0247] Several methods for preparing the compounds of the present invention are described in detail in the following schemes and examples. The starting materials can be purchased commercially or can be prepared by methods known in the literature or as described in detail. It will be understood by those skilled in the art that other synthetic routes can also be used to synthesize the compounds of the present invention. Although the specific starting materials and conditions in the synthetic routes have been described below, they can be easily replaced with other similar starting materials and conditions, and these modifications or variations of the preparation methods of the present invention that result in various isomerizations of the compounds are included within the scope of the present invention. In addition, the preparation methods described below can be further modified according to the present disclosure using conventional chemical methods well known to those skilled in the art. For example, appropriate groups can be protected during the reaction, etc.

[0248] The following process examples are provided to facilitate a further understanding of the preparation methods of the present invention. The specific substances, types, and conditions used are intended to further illustrate the present 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 readily prepared by one of ordinary skill in the art.

[0249] The analytical instruments described in the examples are as follows:

[0250] 1. High Performance Liquid Chromatography (HPLC): Agilent Technologies, 1260 Infinity II instrument

[0251] Column: Agilent Eclipse Plus C18 3.5 μm, 4.6*100 mm

[0252] Mobile phase: A: water + 0.1% phosphoric acid; B: acetonitrile, temperature: 30°C

[0253] Gradient: 10% B to 95% B in 15 min; 95% B 3 min

[0254] Flow rate: 1 mL / min

[0255] 2. Ultra-high performance liquid chromatography-tandem mass spectrometry (LC-MS): Waters ACQUITY H-Class UPLC-SQ Detector2

[0256] Column: ACQUITY BEH C18 1.7μm,2.1*50mm Column

[0257] Mobile phase: A: water + 0.2% formic acid; B: acetonitrile, temperature: 30°C

[0258] Gradient: 10% B to 95% B in 5 min; 95% B 1 min

[0259] Flow rate: 0.5 mL / min

[0260] MS method: ESI positive, negative, mass range (m / z): 100-800

[0261] 3. Gas Chromatography-Tandem Mass Spectrometry (GC-MS): Agilent Technologies, 7890B GC System-5977A MSD equipment

[0262] Column: Agilent Technologies, HP-5MS UI 0.25μm, 30m*0.250mm

[0263] Injector temperature: 250°C

[0264] Column flow rate: Helium 1mL / min

[0265] Method: maintain at 40℃ for 2 minutes, increase the temperature at 20℃ / min to 280℃, maintain at 280℃ for 5 minutes, total time 19 minutes

[0266] MSD transfer line temperature: 280°C

[0267] EI ion source temperature: 230°C, MS quadrupole temperature: 150°C, scan range: 30.00-400.00

[0268] 4. Automatic polarimeter: Use Rudolph Research Analytical, II Automatic Polarimeter Equipment

[0269] Wavelength: 589nm

[0270] Channel length: 50.00mm

[0271] Temperature: 20℃

[0272] The concentration "c" of the compound being tested (in g / 100 mL) and the solvent used.

[0273] In addition, the proton nuclear magnetic resonance spectrum (hereinafter referred to as 1The chemical shift values ​​of H-NMR were measured at 400 MHz (Bruker, AVANCE III HD 400M) in deuterated chloroform solvent (CDCl3) using Me4Si (tetramethylsilane) as a reference substance. When measured in deuterated dimethyl sulfoxide solvent, the chemical shift value data are displayed as "(DMSO-d6)". It should be noted that 1 The symbols in the chemical shift values ​​of H-NMR have the following meanings:

[0274] s: singlet, d: doublet, dd: doublet of doublets, dt: doublet of triplets, td: triplet of doublets, ddd: doublet of doublets, t: triplet, q: quartet, sep: septet, m: multiplet, brs: broad singlet. In the case of two or more stereoisomers, the chemical shift values ​​for resolvable signals are indicated with "and".

[0275] Examples of representative compounds are shown below. The synthesis methods of other compounds are similar and will not be described in detail here.

[0276] The following examples illustrate the present invention in detail.

[0277] Example 1

[0278] Preparation of intermediate II-1

[0279] Step 1: Preparation of intermediate II-1.1:

[0280] 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 500 mL single-necked flask and stirred. 3,5-difluorobenzaldehyde (100 g, 0.7 mol) was added dropwise and allowed to react for 3 hours. After the reaction, the solvent was removed under reduced pressure, and the mixture was extracted twice with 100 mL of dichloromethane. The organic phases were combined and washed once with saturated brine. Drying was performed over anhydrous sodium sulfate, and the solvent was evaporated under reduced pressure to obtain Intermediate II-1.1 (white solid, 108 g).

[0281] Step 2: Preparation of intermediate II-1.2:

[0282] 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 continued in an ice bath for 3 hours. After the reaction, the system was extracted twice with 30 mL of dichloromethane. The organic phases were combined and washed once with saturated brine. After drying over anhydrous sodium sulfate, the solvent was evaporated under reduced pressure to obtain intermediate II-1.2 (white solid, 5 g).

[0283] Step 3: Preparation of intermediate II-1.3:

[0284] At room temperature, add 40% aqueous acetaldehyde solution (110.125 g, 1 mol) and 1,4-dioxane (70 mL) to a 500 mL single-necked flask and stir. Add methyl acrylate (258 g, 3 mol) and triethylenediamine (112.17 g, 1 mol) and allow to react for 3 hours. After the reaction is complete, evaporate the solvent under reduced pressure, extract twice with 200 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 obtain Intermediate II-1.3 (yellow liquid, 85 g).

[0285] Step 4: Preparation of Intermediate II-1.4:

[0286] 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. Intermediate II-1.3 (1.36 g, 10.44 mmol) and sodium bicarbonate (4.4 g, 52.2 mmol) were then added, and the temperature was raised to 50°C for 2 hours. After the reaction, 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 mixture was dried over anhydrous sodium sulfate, and the solvent was evaporated under reduced pressure. The mixture was purified by column chromatography (eluent: petroleum ether:ethyl acetate = 5:1) to obtain intermediate II-1.4 (white solid, 2.6 g).

[0287] Step 5: Preparation of intermediate II-1.5:

[0288] 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. Pyridine (1.46 mL, 18.2 mmol) was then added, followed by dropwise addition of trifluoromethanesulfonic anhydride (2.30 mL, 13.67 mmol), and the mixture was allowed to react at room temperature for 2 hours. After the reaction, the system was extracted twice with 30 mL of dichloromethane, the organic phases were combined, and then washed once with saturated brine. After drying over anhydrous sodium sulfate, the solvent was evaporated under reduced pressure to obtain the crude intermediate II-1.5 (yellow solid, 3.2 g). This was directly used in the next step without further treatment.

[0289] Step 6: Preparation of Intermediate II-1.6:

[0290] 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 stirred at room temperature overnight. After the reaction, 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 evaporated under reduced pressure, and intermediate II-1.6 was purified by column chromatography (eluent: petroleum ether:ethyl acetate = 5:1) to obtain intermediate II-1.6 (white solid, 1.39 g). 1 H 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).

[0291] Step 7: Preparation of Intermediate II-1:

[0292] 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 and stirred to dissolve. A 20% aqueous sodium hydroxide solution (6.72 g, 33.6 mmol) was added and refluxed for 5 hours. After the reaction, the reaction solution was cooled to room temperature and the pH was adjusted to 1-2 with dilute hydrochloric acid (10%). A solid precipitated, which was filtered and dried to obtain intermediate II-1 (5 g, white solid). 1H 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).

[0293] Example 2

[0294] Preparation of intermediate II-19

[0295] Step 1: Preparation of Intermediate II-19.1

[0296] At room temperature, compound 3-chloro-4,5-difluorobenzoic acid (5 g, 25.97 mmol) and dichloromethane (50 mL) were added to a 25 mL single-necked bottle, followed by 2 drops of N,N-dimethylformamide (DMF) and subsequently oxalyl chloride (3.3 mL, 38.95 mmol). Violent release of gas was observed. The mixture was stirred at room temperature for 2 hours, and then the solvent and excess oxalyl chloride were evaporated under reduced pressure. The resulting crude product intermediate II-19.1 was used in the next step without further purification.

[0297] Step 2: Preparation of Intermediate II-19.2

[0298] 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 25 mL single-necked flask, 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 warmed to room temperature and stirred for 2 h. After the reaction was complete, water was added. Stir for 10 min, allow to stand and separate, and the organic phase was dried over anhydrous sodium sulfate and concentrated under reduced pressure. The residue was purified by reverse phase column to obtain intermediate II-19.2 (white solid, 5 g).

[0299] Step 3: Preparation of Intermediate II-19.3

[0300] 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 temperature was cooled to -20°C, and a 1.5 M solution of diisobutylaluminum hydride in toluene (21.3 mL, 31.95 mmol) was added dropwise. The reaction was allowed to proceed for 2 h. After completion of the reaction, a saturated aqueous solution of potassium sodium tartrate was added, and the mixture was extracted with ethyl acetate. The mixture was purified by column chromatography to afford 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).

[0301] Step 4: Preparation of Intermediate II-19.4

[0302] 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 uniform. Intermediate II-19.3 (1.26 g, 7.14 mmol) was then added dropwise and allowed to react for 3 hours. After the reaction, the solvent was removed under reduced pressure, and the mixture was extracted twice with dichloromethane. The combined organic phases were then washed once with saturated brine. The mixture was dried over anhydrous sodium sulfate and the solvent was evaporated under reduced pressure to yield Intermediate II-19.4 (white solid, 1.25 g).

[0303] Step 5: Preparation of Intermediate II-19.5

[0304] 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 continued in an ice bath for 3 hours. After the reaction was completed, the reaction solution was extracted twice with 30 mL of dichloromethane. The organic phases were combined and washed once with saturated brine. After drying over anhydrous sodium sulfate, the solvent was evaporated under reduced pressure to obtain intermediate II-19.5 (yellow oil, 1.5 g).

[0305] Step 6: Preparation of Intermediate II-19.6

[0306] 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. Methyl 3-hydroxy-2-methylenebutanoate (403 mg, 3.1 mmol) and sodium bicarbonate (1.3 g, 15.5 mmol) were then added, and the temperature was raised to 50°C for 2 hours. After the reaction, 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 mixture was dried over anhydrous sodium sulfate, and the solvent was evaporated under reduced pressure. The product was purified by column chromatography (eluent: petroleum ether:ethyl acetate = 5:1) to obtain intermediate II-19.6 (yellow solid, 880 mg).

[0307] Step 7: Preparation of Intermediate II-19.7

[0308] 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. Pyridine (445 μL, 5.5 mmol) was then added, followed by dropwise addition of trifluoromethanesulfonic anhydride (695 μL, 4.13 mmol), and the mixture was allowed to react at room temperature for 2 hours. After the reaction, the reaction solution was extracted twice with 30 mL of dichloromethane, the organic phases were combined, and then washed once with saturated brine. The mixture was dried over anhydrous sodium sulfate and the solvent was evaporated under reduced pressure to obtain the crude intermediate II-19.7 (yellow oil, 1.27 g). The crude product was directly used in the next step without further treatment.

[0309] Step 8: Preparation of Intermediate II-19.8

[0310] 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 stirred at room temperature overnight. After the reaction, 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 evaporated under reduced pressure, and intermediate II-19.8 was purified by column chromatography (eluent: petroleum ether:ethyl acetate = 5:1) to obtain intermediate II-19.8 (oily solid, 497 mg). 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).

[0311] Step 9: Preparation of Intermediate II-19

[0312] 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 and stirred to dissolve. 20% aqueous sodium hydroxide solution (330 mg, 1.65 mmol) was added and allowed to react at room temperature for 1 hour. After the reaction, the pH of the reaction solution was adjusted to 1-2 with dilute hydrochloric acid (10%). A solid precipitated, which 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).

[0313] Example 3

[0314] Preparation of intermediate II-20

[0315] Step 1: Preparation of intermediate II-20.1:

[0316] Intermediate II-19.5 (3 g, 15.7 mmol) and isopropanol (20 mL) were added to a 50 mL reaction flask at room temperature. Methyl methacrylate (1.84 mL, 17.2 mmol) and sodium bicarbonate (6.6 g, 78.5 mmol) were added at room temperature and the mixture was heated to 50°C for 3 h. After completion of the reaction, 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).

[0317] Step 2: Preparation of intermediate II-20:

[0318] 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 and stirred to dissolve. 20% aqueous sodium hydroxide solution (3.76 g, 18.8 mmol) was added and allowed to react at room temperature for 1 hour. After the reaction, the pH of the reaction solution was adjusted to 1-2 with dilute hydrochloric acid (10%). A solid precipitated, which 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).

[0319] Example 4

[0320] Preparation of intermediate II-28

[0321] Step 1: Preparation of intermediate II-28.1:

[0322] Similar to the preparation procedure of intermediate II-1.1, intermediate II-28.1 was prepared by reacting 3,5-dimethoxybenzaldehyde with hydroxylamine hydrochloride.

[0323] Step 2: Preparation of intermediate II-28.2:

[0324] 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. Triethylamine (1.68 g, 13.2 mmol) was then added. The reaction system was stirred in an ice bath for 10 minutes, followed by the slow addition of sodium hypochlorite solution (10% available chlorine) (5.5 mL, 7.4 mmol). The mixture was stirred at 0°C for 1 hour, followed by the addition of methyl methacrylate (553 g, 5.52 mmol). The mixture was stirred at 0°C for 1 hour, and the solvent was evaporated under reduced pressure. Water was added, and the mixture was extracted twice with ethyl acetate. The organic phases were combined and the solvent was evaporated under reduced pressure to obtain intermediate II-28.2 (white solid, 970 mg).

[0325] Step 3: Preparation of intermediate II-28:

[0326] 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 and stirred to dissolve. 20% aqueous sodium hydroxide solution (800 mg, 4 mmol) was added and allowed to react at room temperature for 1 hour. After the reaction, the pH of the reaction solution was adjusted to 1-2 with dilute hydrochloric acid (10%). A solid precipitated, which 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).

[0327] Example 5

[0328] Preparation of intermediate II-35

[0329] Step 1: Preparation of intermediate II-35.1:

[0330] 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 at 0°C. After stirring for 20 minutes, a 20% aqueous potassium hydroxide solution (27 mL, 114 mmol) was added dropwise and allowed to react for 1.5 hours. After completion of the reaction, 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 evaporated under reduced pressure. After purification by column chromatography, Intermediate II-35.1 was obtained as a light yellow oil (2.89 g).

[0331] Step 2: Preparation of intermediate II-35.2:

[0332] 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, and the reaction system was refluxed under a nitrogen atmosphere for 10 hours. After the reaction, the system was cooled to room temperature and diluted with 20 mL of ethyl acetate. The suspended solid was filtered off, the solvent was removed in vacuo, and II-35.2 was purified by column chromatography (petroleum ether:ethyl acetate = 3:1) to obtain II-35.2 as a yellow oil, 2.4 g.

[0333] Step 3: Preparation of intermediate II-35.3:

[0334] 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.

[0335] Step 4: Preparation of intermediate II-35.4:

[0336] Similar to the preparation procedure of intermediate II-1.2, intermediate II-35.4 is prepared by reacting II-35.3 with N-chlorosuccinimide.

[0337] Step 5: Preparation of intermediate II-35.5:

[0338] Similar to the preparation procedure of intermediate II-20.1, intermediate II-35.5 is prepared by reacting II-35.4 with methyl methacrylate.

[0339] Step 6: Preparation of intermediate II-35:

[0340] 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. Lithium hydroxide monohydrate (220 mg, 5.2 mmol) was added to the system and allowed to react for 30 minutes. After the reaction, 1 M hydrochloric acid was added dropwise to adjust the pH to 3-4. Extraction was performed with 20 mL of ethyl acetate. The organic phases were combined, washed once with saturated brine, dried over anhydrous sodium sulfate, and the solvent was evaporated under reduced pressure to obtain II-35 (a light yellow solid, 1.41 g). 1 H 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).

[0341] Example 6

[0342] Preparation of intermediate II-39

[0343] Step 1: Preparation of intermediate II-39.1:

[0344] Intermediate II-19.5 (2.44 g, 12.7 mmol) and isopropanol (10 mL) were added to a 50 mL reaction flask at room temperature. Methyl methoxyacrylate (1.47 mg, 12.7 mmol) and sodium bicarbonate (5.3 g, 63.5 mmol) were added at room temperature and the mixture was heated to 50°C for 3 h. After completion of the reaction, 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).

[0345] Step 2: Preparation of intermediate II-39:

[0346] 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 added and allowed to react at room temperature for 1 hour. After the reaction, the pH of the reaction solution was adjusted to 1-2 with dilute hydrochloric acid (10%). A solid precipitated, which was filtered and dried to obtain intermediate II-39 (a 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).

[0347] Example 7

[0348] Preparation of Intermediate II-69

[0349] Step 1: Preparation of intermediate II-69.1:

[0350] To a 500 mL three-necked flask, 1-bromo-3-chloro-5-(trifluoromethyl)toluene (20 g, 77.09 mmol) and tetrahydrofuran (80 mL) were added. A solution of isopropylmagnesium chloride in tetrahydrofuran (2 mol / L) (115.6 mL, 231.27 mmol) was added under ice-cooling. The mixture was stirred at room temperature for 1 hour, until it turned pink. N,N-dimethylformamide (16.9 g, 231.27 mmol) was added under ice-cooling and stirred at room temperature overnight. After completion of the reaction, excess dilute hydrochloric acid (10%) was added dropwise. The insoluble matter was removed by filtration, and the filtrate was desolvated to remove the solvent. The filtrate was extracted twice with 1000 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 evaporated under reduced pressure to obtain Intermediate II-69.1 (yellow-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).

[0351] Step 2: Preparation of intermediate II-69.2:

[0352] 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).

[0353] Step 3: Preparation of intermediate II-69.3:

[0354] Similar to the preparation procedure of intermediate II-1.2, intermediate II-69.2 is reacted with N-chlorosuccinimide to prepare intermediate II-69.3. 1 HNMR(400MHz,DMSO)δ12.94(s,1H),8.07–7.92(m,3H).

[0355] Step 4: Preparation of intermediate II-69:

[0356] At room temperature, intermediate II-69.3 (5 g, 19 mmol) and isopropanol (20 mL) were added to a 50 mL single-necked bottle and stirred to dissolve. 2-(Trifluoromethyl)acrylic acid (2.67 g, 19 mmol) and sodium bicarbonate (3.66 g, 97.5 mmol) were then added, and the temperature was raised to 50°C for 2 hours. After the reaction was completed, the insoluble matter was removed by filtration, and the mixture was extracted twice with 30 mL of dichloromethane. The organic phases were combined and washed once with saturated brine. The mixture was dried over anhydrous sodium sulfate, the solvent was evaporated under reduced pressure, and the intermediate II-69 (white solid, 5.1 g) was obtained by purification 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).

[0357] Example 8

[0358] Preparation of intermediate II-77

[0359] Step 1: Preparation of intermediate II-77.1:

[0360] At room temperature, intermediate II-19.5 (1 g, 5.2 mmol) and isopropanol (20 mL) were added to a 50 mL reaction flask. Methyl 2-(chloromethyl)acrylate (0.7 g, 5.3 mmol) and sodium bicarbonate (2.2 g, 26.2 mmol) were added at room temperature. The temperature was raised to 50°C and the reaction was allowed to react for 3 h. After completion of the reaction, the product was purified by column chromatography to obtain intermediate II-77.1 (white solid, 1.4 g).

[0361] Step 2: Preparation of intermediate II-77:

[0362] 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 added and allowed to react at room temperature for 1 hour. After completion of the reaction, the pH of the system was adjusted to 1-2 with dilute hydrochloric acid (10%). The organic phase was extracted with ethyl acetate and dried over anhydrous sodium sulfate. The solvent was evaporated 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).

[0363] Example 9

[0364] Preparation of intermediate II-110

[0365] Step 1: Preparation of intermediate II-110.1:

[0366] 3-Bromo-5-fluorophenol (5 g, 26.18 mmol) was dissolved in isopropanol (15 mL) at room temperature. 20% aqueous sodium hydroxide solution (7.8 g, 39.27 mmol) was added at room temperature and stirred for 30 minutes. Difluorochloromethane (CHClF2) gas was introduced for replacement. The reaction was allowed to react 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 evaporated under reduced pressure, 20 mL of water was added, and a Dean-Stark apparatus was placed on it. The temperature was raised to 100°C and refluxed. The lower liquid in the Dean-Stark apparatus was collected to obtain intermediate II-110.1 (colorless oil, 4.1 g).

[0367] Step 2: Preparation of intermediate II-110.2:

[0368] Intermediate II-110.1 (1 g, 4.15 mmol) was dissolved in tetrahydrofuran (2 mL) under ice bath. Isopropylmagnesium chloride in tetrahydrofuran (2M) (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 reacted at room temperature for 1 hour. 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).

[0369] Step 3: Preparation of intermediate II-110.3:

[0370] 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.

[0371] Step 4: Preparation of intermediate II-110.4:

[0372] Similar to the preparation procedure of intermediate II-1.2, intermediate II-110.3 is reacted with N-chlorosuccinimide to prepare intermediate II-110.4.

[0373] Step 5: Preparation of intermediate II-110.5:

[0374] 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. Methyl 2-(chloromethyl)acrylate (2.9 g, 25.0 mmol) and sodium bicarbonate (10.4 g, 124.1 mmol) were added at room temperature. The temperature was raised to 50°C and the reaction was allowed to react for 3 h. After completion of the reaction, intermediate II-110.5 (white solid, 1.4 g) was purified by column chromatography.

[0375] Step 6: Preparation of intermediate II-110.6

[0376] The 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, the reaction solution was added to a saturated aqueous sodium bicarbonate solution and extracted twice with dichloromethane. The mixture was dried over anhydrous sodium sulfate, the solvent was evaporated under reduced pressure, and the mixture was purified by column chromatography to obtain the intermediate II-110.6 (white solid, 700 mg).

[0377] Step 7: Preparation of Intermediate II-110

[0378] 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 and stirred to dissolve. A 20% aqueous solution of lithium hydroxide monohydrate (95 mg, 2.27 mmol) was added and allowed to react at room temperature for 1 hour. After completion of the reaction, the pH of the system was adjusted to 1-2 with dilute hydrochloric acid (10%). The product was extracted with ethyl acetate and dried over anhydrous sodium sulfate. The solvent was evaporated under reduced pressure 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).

[0379] Example 10

[0380] Preparation of intermediate II-115

[0381] Step 1: Preparation of intermediate II-115.1:

[0382] Similar to the preparation procedure of intermediate II-110.5, intermediate II-1.2 is reacted with methyl 2-(hydroxymethyl)acrylate to prepare intermediate II-115.1. Step 2: Preparation of intermediate II-115.2:

[0383] 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 at room temperature. After completion of the reaction, the reaction system was quenched with 30 mL of saturated sodium bicarbonate solution. The suspended solid was removed by filtration, and the filtrate was extracted twice with 30 mL of dichloromethane. The organic phases were combined and purified by column chromatography to obtain Intermediate II-115.2 (white solid, 1.1 g).

[0384] Step 3: Preparation of intermediate II-115.3:

[0385] 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, stirred evenly, and refluxed at 50°C for 24 hours. After completion of the reaction, 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 on a reverse-phase column to obtain intermediate II-115.3 (yellow oil, 700 mg).

[0386] Step 4: Preparation of intermediate II-115:

[0387] 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. Lithium hydroxide monohydrate (111 mg, 2.6 mmol) was added and allowed to react for 30 min. After the reaction, 1 M hydrochloric acid was added dropwise to adjust the pH to 3-4. Extraction was performed 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 evaporated under reduced pressure to yield II-115 (yellow solid, 650 mg). 1 H 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).

[0388] Example 11

[0389] Preparation of intermediate II-136

[0390] Step 1: Preparation of intermediate II-136.1:

[0391] 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 and stirred. The mixture was allowed to react at room temperature for 1.5 h. After completion of the reaction, the solvent was removed under reduced pressure. The mixture was extracted twice with 30 mL of dichloromethane. The combined organic phases were then washed once with saturated brine. The mixture was dried over anhydrous sodium sulfate and the solvent was evaporated under reduced pressure to obtain Intermediate II-136.1 (white solid, 5.4 g).

[0392] Step 2: Preparation of intermediate II-136.2:

[0393] 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, the system was extracted twice with 30 mL of dichloromethane. The combined organic phases were washed once with saturated brine. Drying over anhydrous sodium sulfate and the solvent was evaporated under reduced pressure to obtain intermediate II-136.2 (white solid, 6.1 g).

[0394] Step 3: Preparation of intermediate II-136.3:

[0395] Similar to the preparation procedure of intermediate II-1.4, intermediate II-136.2 is reacted with intermediate II-1.3 to prepare intermediate II-136.3.

[0396] Step 4: Preparation of intermediate II-136.4:

[0397] 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. The mixture was stirred at -10°C for 20 min. Dess-Martin periodinane (3 g, 7.08 mmol) was then slowly added to the system. After the addition was complete, the mixture was transferred to room temperature and stirred for 2 h. After the reaction, 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 on a reverse-phase column to obtain intermediate II-136.4 (white solid, 1.35 g).

[0398] Step 5: Preparation of intermediate II-136.5:

[0399] 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, 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 completion of the reaction, 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, the solvent was evaporated under reduced pressure, and the mixture was purified by column chromatography to obtain intermediate II-136.5 (pale yellow solid, 500 mg).

[0400] Step 6: Preparation of intermediate II-136:

[0401] 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. Lithium hydroxide monohydrate (68 mg, 1.6 mmol) was added and allowed to react for 30 minutes. After the reaction, 1 M hydrochloric acid was added dropwise to adjust the pH to 3-4. The mixture was 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 evaporated under reduced pressure to yield 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).

[0402] Example 12

[0403] Preparation of intermediate II-155:

[0404] Step 1: Preparation of intermediate II-155.1:

[0405] At room temperature, intermediate II-136.4 (1.0 g, 3.16 mmol) and dichloromethane (10 mL) were added to a 50 mL microwave reaction bottle, cooled to -10 ° C with stirring, and diethylaminosulfur trifluoride (DSAT) (1.27 g, 7.9 mmol) was slowly added dropwise. After the addition was complete, the mixture 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 extracted twice with 30 mL of dichloromethane. The organic phases were combined, the solvent was evaporated under reduced pressure, and the intermediate II-136.5 (yellow oil, 540 mg) was obtained after purification by column chromatography.

[0406] Step 2: Preparation of intermediate II-155:

[0407] 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 thoroughly. Lithium hydroxide monohydrate (78 mg, 1.9 mmol) was added and allowed to react for 30 min. After the reaction, hydrochloric acid (1 M) was added dropwise to adjust the pH to 3-4. Extraction was performed 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 evaporated under reduced pressure to yield 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).

[0408] Referring to the above method, other intermediates II can be obtained by using corresponding substituted benzaldehydes, which can be purchased on the market or easily prepared by ordinary technicians in this field. 1 See Table A for H NMR.

[0409] Table A

[0410] The intermediate II prepared above can be separated by a chiral column to obtain enantiomers, which are S configuration and R configuration, respectively.

[0411] Analytical separation methods:

[0412] Method A:

[0413] Instrument: Agilent 1260 Infinity II

[0414] Column: Chiralpak AD-H, 250 × 4.6 mm ID, 5 μm

[0415] Mobile phase: A represents n-hexane (0.2% formic acid), B represents isopropanol, isocratic: B% = 25%

[0416] Flow rate: 1.0 mL / min, column temperature: 30°C

[0417] Wavelength: 265nm

[0418] Run time: 20 minutes

[0419] Method B:

[0420] Instrument: Agilent 1260 Infinity II

[0421] Column: Chiralpak AD-H, 250 × 4.6 mm ID, 5 μm

[0422] Mobile phase: A represents n-hexane (0.2% formic acid), B represents isopropanol, isocratic: B% = 20%

[0423] Flow rate: 1.0 mL / min, column temperature: 30°C

[0424] Wavelength: 265nm

[0425] Run time: 20 minutes

[0426] Method C:

[0427] Instrument: Agilent 1260 Infinity II

[0428] Column: Chiralpak AD-H, 250 × 4.6 mm ID, 5 μm

[0429] Mobile phase: A represents n-hexane (0.2% formic acid), B represents isopropanol, isocratic: B% = 15%

[0430] Flow rate: 1.0 mL / min, column temperature: 30°C

[0431] Wavelength: 265nm

[0432] Run time: 20 minutes

[0433] Method D:

[0434] Instrument: Agilent 1260 Infinity

[0435] Column: Chiralpak AD-H, 250 × 4.6 mm ID, 5 μm

[0436] Mobile phase: A represents n-hexane (0..05% trifluoroacetic acid), B represents isopropanol, isocratic: B% = 12%

[0437] Flow rate: 1.0 mL / min, column temperature: 30°C

[0438] Wavelength: 265nm

[0439] Run time: 20 minutes

[0440] Method E:

[0441] Instrument: Agilent 1260 Infinity

[0442] Column: Chiralpak AD-H, 250 × 4.6 mm ID, 5 μm

[0443] Mobile phase: A represents n-hexane, B represents isopropanol, isocratic: B% = 25%

[0444] Flow rate: 1.0 mL / min, column temperature: 30°C

[0445] Wavelength: 265nm

[0446] Run time: 20 minutes

[0447] Method F:

[0448] Instrument: Agilent 1260 Infinity

[0449] Column: Chiralpak AD-H, 250 × 4.6 mm ID, 5 μm

[0450] Mobile phase: A represents n-hexane, B represents isopropanol, isocratic: B% = 30%

[0451] Flow rate: 1.0 mL / min, column temperature: 30°C

[0452] Wavelength: 265nm

[0453] Run time: 20 minutes

[0454] Method G:

[0455] Instrument: Agilent 1260 Infinity

[0456] Column: Chiralpak AD-H, 250 × 4.6 mm ID, 5 μm

[0457] Mobile phase: A represents n-hexane, B represents isopropanol, isocratic: B% = 10%

[0458] Flow rate: 1.0 mL / min, column temperature: 30°C

[0459] Wavelength: 265nm

[0460] Run time: 20 minutes

[0461] Method H:

[0462] Instrument: Agilent 1260 Infinity

[0463] Column: Chiralpak AD-H, 250 × 4.6 mm ID, 5 μm

[0464] Mobile phase: A represents n-hexane, B represents isopropanol, isocratic: B% = 25%

[0465] Flow rate: 1.0 mL / min, column temperature: 30°C

[0466] Wavelength: 265nm

[0467] Run time: 20 minutes

[0468] Preparative separation methods:

[0469] Method 1:

[0470] Instrument:Gilson GX-281

[0471] Column: Chiralpak AD-H, 250×30mm ID, 5μm

[0472] Mobile phase: A represents n-hexane (0.2% formic acid), B represents isopropanol, isocratic: B% = 25% flow rate: 31 mL / min, column temperature: 30°C

[0473] Wavelength: 265nm

[0474] Run time: 20 minutes

[0475] Method 2:

[0476] Instrument:Gilson GX-281

[0477] Column: Chiralpak AD-H, 250×30mm ID, 5μm

[0478] Mobile phase: A represents n-hexane (0.2% formic acid), B represents isopropanol, isocratic: B% = 20% flow rate: 33 mL / min, column temperature: 30°C

[0479] Wavelength: 265nm

[0480] Run time: 20 minutes

[0481] Method 3:

[0482] Instrument:Gilson GX-281

[0483] Column: Chiralpak AD-H, 250×30mm ID, 5μm

[0484] Mobile phase: A represents n-hexane (0.2% formic acid), B represents isopropanol, isocratic: B% = 15% flow rate: 34 mL / min, column temperature: 30°C

[0485] Wavelength: 265nm

[0486] Run time: 20 minutes

[0487] Method 4:

[0488] Instrument:Gilson GX-281

[0489] Column: Chiralpak AD-H, 250×30mm ID, 5μm

[0490] Mobile phase: A represents n-hexane (0.05% trifluoroacetic acid), B represents isopropanol, gradient: B% = 12%

[0491] Flow rate: 34 mL / min, column temperature: 30°C

[0492] Wavelength: 265nm

[0493] Run time: 20 minutes

[0494] Intermediate II-1 can be separated into enantiomers II-1-A and II-1-B (Method 1):

[0495] Weigh 5.0 g of intermediate II-1 (purity 95%), dissolve the sample with n-hexane: isopropanol = 75:25, prepare a 40 mg / mL solution, and the injection volume is 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.

[0496] II-1-A: Retention time: 8.82 min (Method 1), 100 ee% (Method A),

[0497] II-1-B: Retention time: 6.19 min (Method 1), 100 ee% (Method A),

[0498] The above method can be used to obtain single chiral isomers of other intermediates II, and some intermediates (II) are shown in Table B.

[0499] Table B

[0500] Example I-10

[0501] Preparation of compound I-10

[0502] Step 1: Preparation of intermediate I-10.1:

[0503] At room temperature, intermediate II-1 (1.0 g, 3.95 mmol), oxalyl chloride (750 mg, 5.95 mmol), dichloromethane (15 mL), and N,N-dimethylformamide (3 drops) were added to a 100 mL single-necked flask. The reaction system was stirred under a nitrogen atmosphere for 30 minutes. After completion of the reaction, the solvent and excess oxalyl chloride were evaporated under reduced pressure to yield intermediate I-10.1 (yellow oil, 1 g).

[0504] Step 2: Preparation of intermediate I-10.2:

[0505] At room temperature, commercially available cis-3-aminocyclobutanecarboxylic acid methyl ester hydrochloride (250 mg, 1.51 mmol), triethylamine (292 mg, 2.9 mmol), and 2 mL of dichloromethane were added to a 25 mL single-necked flask. Intermediate I-10.1 (300 mg, 1.1 mmol) dissolved in 2 mL of dichloromethane was added at 0°C. The mixture was stirred for 6 h while warming to room temperature. After the reaction was complete, water was added and stirred. The mixture was allowed to stand for stratification. The lower organic phase was separated, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. Reverse phase preparative purification was then performed to obtain intermediate I-10.2 (white solid, 200 mg).

[0506] Step 3: Preparation of intermediate I-10.3:

[0507] At room temperature, intermediate I-10.2 (178 mg, 0.488 mmol), tetrahydrofuran (2 mL), and water (0.5 mL) were added to a 25 mL single-necked flask and stirred to dissolve. Lithium hydroxide monohydrate (23 mg, 0.55 mmol) was added and allowed to react at room temperature for 1 hour. After the reaction, the pH of the system was adjusted to 1-2 with dilute hydrochloric acid (10%). The precipitated solid was filtered and the filter cake dried to obtain intermediate I-10.3 (white solid, 120 mg). Step 4: Preparation of Intermediate I-10.4:

[0508] At room temperature, intermediate I-10.3 (500 mg, 1.48 mmol) and dichloromethane (5 mL) were added to a 25 mL single-necked bottle, followed by 2 drops of N,N-dimethylformamide and subsequent oxalyl chloride (200 μL, 2.32 mmol). Violent gas release was observed. The mixture was stirred at room temperature for 2 hours, and then the solvent and excess oxalyl chloride were evaporated under reduced pressure. The resulting crude intermediate I-10.4 was used in the next step without further purification.

[0509] Step 5: Preparation of intermediate I-10.5:

[0510] At room temperature, 2-(Methylthio)ethanol (273 mg, 2.96 mmol), triethylamine (505 mg, 5 mmol), and 2 mL of dichloromethane were added to a 25 mL single-necked flask. A solution of the intermediate I-10.4 from the previous step in dichloromethane (1 mL) was added at 0°C. The mixture was stirred for 2 h while warming to room temperature. After the reaction was complete, water was added and stirred, and the mixture was allowed to stand for stratification. The lower organic phase was separated, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was purified by reverse phase preparative reaction to obtain intermediate I-10.5 (white solid, 355 mg).

[0511] Step 6: Preparation of intermediate I-10.6:

[0512] At room temperature, intermediate I-10.5 (145 mg, 0.342 mmol) and dichloromethane (5 mL) were added to a 25 mL single-necked flask and stirred in an ice bath. m-Chloroperbenzoic acid (69 mg, 0.342 mmol, 85%) was added and allowed to react for 5 hours. After completion of the reaction, intermediate I-10.6 was purified by column chromatography (dichloromethane:acetic acid = 99:1) to obtain intermediate I-10.6 (white solid, 102 mg).

[0513] Step 7: Preparation of compound I-10:

[0514] At room temperature, intermediate I-10.6 (130 mg, 0.306 mmol) and dichloromethane (5 mL) were added to a 25 mL single-necked flask and stirred. m-Chloroperbenzoic acid (155 mg, 0.766 mmol, 85%) was added and the mixture was heated to 40°C for 2 hours. After completion of the reaction, the mixture was purified by column chromatography (dichloromethane:acetic acid = 99:1) to obtain compound I-10 (white solid, 70 mg). 1 H NMR (400MHz, DMSO) δ8.53(d,J=7.7Hz,1H),7.47–7.37(m,3H),6.12(dd,J=17.3,10.7Hz,1H),5.33(dd,J=29.3,14.0Hz,2H),4.37(t,J=5 .8Hz,2H),4.23–4.12(m,1H),3.87(d,J=17.8Hz,1H),3.50(dd,J=15.5,11.7Hz,3H),3.01(s,3H),2.93–2.79(m,1H),2.44–2.20(m,4H).

[0515] Example I-20

[0516] Preparation of compound I-20

[0517] Step 1: Preparation of intermediate I-20.1:

[0518] At room temperature, intermediate II-1-A (2.0 g, 7.9 mmol), oxalyl chloride (1.5 g, 11.9 mmol), dichloromethane (15 mL), and N,N-dimethylformamide (3 drops) were added to a 100 mL single-necked flask. The reaction system was stirred under a nitrogen atmosphere for 30 minutes. After completion of the reaction, the solvent and excess oxalyl chloride were removed in vacuo to yield intermediate I-20.1 (yellow oil, 2.1 g).

[0519] Step 2: Preparation of intermediate I-20.2:

[0520] At 0°C, cis-3-aminocyclobutanecarboxylic acid methyl ester hydrochloride (1.9 g, 11.7 mmol), dichloromethane (15 mL), and triethylamine (3.9 g, 39 mmol) were added to a 100 mL single-necked bottle and stirred for 20 minutes. Then, a dichloromethane (5 mL) solution of intermediate I-20.1 (2.1 g, 7.8 mmol) was added dropwise to the system. After the addition was complete, the mixture was stirred at room temperature for 2 hours. After the reaction was completed, it was extracted twice with 30 mL of dichloromethane. The organic phases were combined, washed once with saturated brine, dried over anhydrous sodium sulfate, and the solvent was evaporated under reduced pressure. The mixture was purified by column chromatography (petroleum ether / ethyl acetate) to obtain intermediate I-20.2 (light yellow solid, 2.7 g).

[0521] Step 3: Preparation of intermediate I-20.3:

[0522] At room temperature, intermediate I-20.2 (2.7 g, 7.4 mmol), tetrahydrofuran (10 mL), and water (20 mL) were added to a 100 mL single-necked flask and stirred thoroughly. Lithium hydroxide monohydrate (342 mg, 8.2 mmol) was added and allowed to react for 30 min. After the reaction, 1 M hydrochloric acid was added dropwise to adjust the pH to 3-4. The mixture was extracted with 30 mL of ethyl acetate. The combined organic phases were washed once with saturated brine, dried over anhydrous sodium sulfate, and the solvent was evaporated under reduced pressure to yield intermediate I-20.3 (white solid, 2.55 g).

[0523] Step 4: Preparation of intermediate I-20.4:

[0524] At room temperature, intermediate I-20.3 (200 mg, 0.57 mmol), oxalyl chloride (109 mg, 0.86 mmol), dichloromethane (4 mL), and N,N-dimethylformamide (2 drops) were added to a 25 mL single-necked flask. The reaction system was stirred under a nitrogen atmosphere for 30 minutes. After completion of the reaction, the solvent and excess oxalyl chloride were removed in vacuo to yield intermediate I-20.4 (yellow solid, 203 mg).

[0525] Step 5: Preparation of compound I-20:

[0526] At room temperature, 3-hydroxypropionitrile (158 mg, 2.2 mmol) and dichloromethane (2 mL) were added to a 25 mL single-necked bottle. After thorough stirring, a dichloromethane (3 mL) solution of the intermediate I-20.4 (203 mg, 0.55 mmol) was added dropwise to the system and stirred for 2 hours. After the reaction was completed, the solvent was evaporated under reduced pressure and the residue was purified by a reverse phase column (acetonitrile / water) to obtain compound I-20 (white solid, 177 mg). 1 H NMR (400MHz, CDCl3) δ7.21-7.13(m,2H),7.03(d,J=8.3Hz,1H),6.89(tt,J=8.7,2 .3Hz,1H),6.15(dd,J=17.2,10.7Hz,1H),5.52(d,J=17.2Hz,1H),5.34(d,J=10.7H z,1H),4.44-4.33(m,1H),4.30(t,J=6.3Hz,2H),3.90(d,J=17.2Hz,1H),3.31(d, J=17.3Hz,1H),2.90(tt,J=9.5,7.9Hz,1H),2.79-2.58(m,4H),2.31-2.09(m,2H).

[0527] Example I-253

[0528] Preparation of Compound I-253

[0529] Step 1: Preparation of intermediate I-253.1:

[0530] At room temperature, intermediate II-70-A (350 mg, 0.97 mmol) was dissolved in dichloromethane (5 mL), N,N-dimethylformamide (0.1 mL) was added, and oxalyl chloride (184.5 mg, 1.45 mmol) was added dropwise. The mixture was stirred at room temperature for 1 h to obtain a dichloromethane solution of intermediate I-253.1, which was used directly in the next step without additional treatment.

[0531] Step 2: Preparation of intermediate I-253.2:

[0532] At room temperature, cis-3-aminocyclobutanecarboxylic acid methyl ester hydrochloride (176.6 mg, 1.07 mmol) was suspended in dichloromethane (5 mL), and triethylamine (500.3 mg, 4.94 mmol) was added and reacted for 30 min. A dichloromethane solution of the first-step intermediate I-253.1 was added dropwise under ice bath, and the mixture was slowly returned to room temperature while stirring for 40 minutes. After the reaction, water was added to the system, stirred, and allowed to stand for stratification. The lower organic phase was separated, desolvated, and purified by column chromatography to obtain intermediate I-253.2 (white solid, 350 mg).

[0533] Step 3: Preparation of intermediate I-253.3:

[0534] At room temperature, the intermediate I-253.2 (350 mg, 0.74 mmol) was dissolved in tetrahydrofuran (10 mL), and an aqueous solution (10 mL) of lithium hydroxide monohydrate (37.3 mg, 0.89 mmol) was added dropwise under ice bath. The mixture was slowly returned to room temperature while stirring for 40 min. After the reaction was completed, the pH value was adjusted to 1-2 with dilute hydrochloric acid (10%), and saturated aqueous sodium chloride solution was added. The mixture was extracted with ethyl acetate, and the organic phase was dried over anhydrous sodium sulfate. The solvent was evaporated under reduced pressure to obtain the intermediate I-253.3 (white solid, 340 mg).

[0535] Step 4: Preparation of intermediate I-253.4:

[0536] At room temperature, intermediate I-253.3 (150 mg, 0.33 mmol) was dissolved in dichloromethane (5 mL), N,N-dimethylformamide (0.1 mL) was added, and oxalyl chloride (62.31 mg, 0.49 mmol) was added dropwise. The mixture was stirred at room temperature for 1 h to obtain a dichloromethane solution of intermediate I-253.4.

[0537] Step 5: Preparation of compound I-253:

[0538] At room temperature, the dichloromethane solution of the intermediate I-253.4 in the previous step was added dropwise to cyclopentanol (1.5 mL) and reacted at room temperature for 2 hours. After the reaction was completed, the solvent was evaporated under reduced pressure and the residue was purified by column chromatography to obtain compound I-253 (white solid, 117 mg). 1H NMR (400MHz, CDCl3) δ7.41–7.31(m,2H),7.22(d,J=8.3Hz,1H),7.09(dd,J=8.5,2.5Hz,1H),5.23–5.11(m,1H),4.47–4.34(m,1H),3.98( d,J=18.1Hz,1H),3.76(d,J=18.1Hz,1H),2.91–2.75(m,1H),2.74–2.54(m,2H),2.27–2.15(m,2H),1.93–1.78(m,3H),1.76–1.55(m,6H).

[0539] Example I-364

[0540] Preparation of Compound I-364

[0541] Step 1: Preparation of intermediate I-364.1:

[0542] At room temperature, intermediate II-1 (150 mg, 0.59 mmol), dichloromethane (5 mL), and N,N-dimethylformamide (0.2 mL) were added to a dry, nitrogen-filled single-necked bottle and stirred to dissolve. Oxalyl chloride (113 mg, 0.88 mmol) was added, and a large amount of bubbles were generated during the addition. The mixture was stirred at room temperature for 20 minutes to obtain a dichloromethane solution of intermediate I-364.1, which was used directly in the next step without additional treatment.

[0543] Step 2: Preparation of compound I-364:

[0544] At room temperature, methyl trans-3-aminocyclobutanecarboxylate hydrochloride (107 mg, 0.65 mmol), triethylamine (239 mg, 2.37 mmol), and dichloromethane (5 mL) were added sequentially to a single-necked flask and stirred thoroughly for 20 minutes. Under an ice bath, a dichloromethane solution of intermediate I-364.1 from the previous step was added dropwise to the system and stirred at room temperature for 30 minutes. After the reaction was complete, the solvent was evaporated under reduced pressure, and the product was purified by high-pressure reverse phase chromatography to yield compound I-364 (white solid, 206 mg). 1H NMR (400MHz, DMSO) δ8.57(d,J=7.9Hz,1H),7.45–7.37(m,3H),6.19–6.05(m,1H),5.42–5.25(m,2H),4.40(dd,J=16 .1,8.1Hz,1H),3.87(d,J=17.8Hz,1H),3.62(s,3H),3.53(d,J=17.8Hz,1H),3.05–2.93(m,1H),2.41–2.25(m,4H).

[0545] Example I-385

[0546] Preparation of Compound I-385

[0547] Step 1: Preparation of intermediate I-385.1:

[0548] Under N2 protection, intermediate II-34 (150 mg, 0.52 mmol), dichloromethane (5 mL), and N,N-dimethylformamide (0.2 mL) were added to a dry single-necked bottle and stirred at room temperature to dissolve. Oxalyl chloride (113 mg, 0.88 mmol) was added. A large amount of bubbles were generated during the addition. Stir at room temperature for 20 minutes to obtain a dichloromethane solution of intermediate I-385.1, which was used without treatment.

[0549] Step 2: Preparation of compound I-385:

[0550] At room temperature, cis-4-aminotetrahydrofuran-2-carboxylic acid methyl ester hydrochloride (130 mg, 0.72 mmol), triethylamine (290 mg, 2.88 mmol), and dichloromethane (5 mL) were added sequentially to a single-necked flask. The reaction system was left at room temperature and stirred thoroughly for 20 minutes. After the reaction solution clarified, a dichloromethane solution of intermediate I-385.1 was added dropwise and stirred at room temperature for 30 minutes. The reaction was monitored for completion by TLC. The reaction was stopped, the solvent was evaporated under reduced pressure, and the product was purified by high-pressure reverse phase purification to yield compound I-385 (a white powdery solid, 180 mg, a mixture of four optical isomers).

[0551] 1H NMR(400MHz,Chloroform-d)δ7.54–7.43(m,1H),7.24–7.17(m,2H),6.97–6.91(m,1H),6.55(t,J=72.7Hz,1H),4.64–4.50(m,2H),4.07–3. 99(m,1H),3.99–3.87(m,1H),3.85–3.71(m,4H),3.18(dd,J=17.3,3.2Hz,1H),2.61–2.48(m,1H),2.15–1.98(m,2H),1.70(d,J=9.4Hz,3H).

[0552] Compound I-385 was separated by chiral SFC (Column: Chiralpak IC; Column Size: 250*60mm, 10um; Injection: 1mL; Mobile Phase: CO2:isopropanol = 75:25; Flow rate: 80mL / min; Wavelength: UV 220nm; Temperature: 40°C; Sample solution: 4mg / mL in methanol / dichloromethane) to obtain four optical isomers:

[0553] Optical isomer 1:

[0554] 1 H NMR(400MHz,Chloroform-d))δ7.47(d,J=7.9Hz,1H),7.25–7.17(m,2H),6.94(dt ,J=9.0,2.0Hz,1H),6.55(t,J=72.7Hz,1H),4.61–4.52(m,2H),4.01(dd,J=9.5,5 .2Hz,1H),3.90(dd,J=9.5,2.2Hz,1H),3.84(s,3H),3.75(d,J=17.3Hz,1H),3.19 (d,J=17.3Hz,1H),2.63–2.50(m,1H),2.11(dt,J=13.8,2.6Hz,1H),1.69(s,3H).

[0555] Optical isomer 2:

[0556] 1H NMR(400MHz,Chloroform-d))δ7.51(d,J=8.1Hz,1H),7.24–7.16(m,2H),6.94(dt ,J=9.0,2.1Hz,1H),6.55(t,J=72.7Hz,1H),4.64–4.51(m,2H),4.05(dd,J=9.4,5 .2Hz,1H),3.96(dd,J=9.4,2.1Hz,1H),3.78(s,3H),3.76(d,J=17.3Hz,1H),3.18 (d,J=17.3Hz,1H),2.59–2.48(m,1H),2.01(dt,J=13.8,2.6Hz,1H),1.72(s,3H).

[0557] Optical isomer 3:

[0558] 1 H NMR(400MHz,Chloroform-d))δ7.47(d,J=7.9Hz,1H),7.25–7.17(m,2H),6.94(dt ,J=9.0,2.0Hz,1H),6.55(t,J=72.7Hz,1H),4.61–4.52(m,2H),4.01(dd,J=9.5,5 .2Hz,1H),3.90(dd,J=9.5,2.2Hz,1H),3.84(s,3H),3.75(d,J=17.3Hz,1H),3.19 (d,J=17.3Hz,1H),2.63–2.50(m,1H),2.11(dt,J=13.8,2.6Hz,1H),1.69(s,3H).

[0559] Optical isomer 4:

[0560] 1 H NMR(400MHz,Chloroform-d))δ7.51(d,J=8.1Hz,1H),7.24–7.16(m,2H),6.94(dt ,J=9.0,2.1Hz,1H),6.55(t,J=72.7Hz,1H),4.64–4.51(m,2H),4.05(dd,J=9.4,5 .2Hz,1H),3.96(dd,J=9.4,2.1Hz,1H),3.78(s,3H),3.76(d,J=17.3Hz,1H),3.18 (d,J=17.3Hz,1H),2.59–2.48(m,1H),2.01(dt,J=13.8,2.6Hz,1H),1.72(s,3H).

[0561] Example I-404

[0562] Preparation of Compound I-404

[0563] Step 1: Preparation of intermediate I-404.1:

[0564] At room temperature, intermediate II-1-A (200 mg, 0.79 mmol), oxalyl chloride (150 mg, 1.19 mmol), dichloromethane (5 mL), and N,N-dimethylformamide (1 drop) were added to a 100 mL single-necked flask. The reaction system was stirred under a nitrogen atmosphere for 30 minutes. After completion of the reaction, the solvent and excess oxalyl chloride were removed under reduced pressure to yield intermediate I-404.1 (yellow oil, 210 mg).

[0565] Step 2: Preparation of compound I-404:

[0566] At 0°C, (1R,3S)-3-aminocyclopentanecarboxylic acid methyl ester hydrochloride (200 mg, 1.11 mmol), dichloromethane (5 mL), and triethylamine (337 mg, 3.33 mmol) were added to a 50 mL single-necked flask and stirred for 20 minutes. A solution of intermediate I-404.1 (210 mg, 0.78 mmol) in dichloromethane (3 mL) was then added dropwise. After the addition was complete, the mixture was stirred at room temperature for 2 hours. After the reaction was complete, the mixture was extracted twice with 30 mL of dichloromethane. The organic phases were combined, washed once with saturated brine, dried over anhydrous sodium sulfate, and the solvent was evaporated under reduced pressure. The mixture was purified by column chromatography (petroleum ether / ethyl acetate) to give intermediate I-404 (white solid, 270 mg). 1 H NMR (400MHz, DMSO) δ8.15 (d, J=7.7Hz, 1H), 7.49–7.35 (m, 3H), 6.14 (dd, J=17.3, 10. 6Hz,1H),5.37(d,J=17.3Hz,1H),5.30(d,J=10.6Hz,1H),4.11(dt,J=14.4,7.2Hz,1H ),3.88(d,J=17.7Hz,1H),3.59(s,3H),3.53(d,J=17.8Hz,1H),2.86–2.74(m,1H),2. 12–2.00(m,1H),1.88–1.78(m,3H),1.73(dt,J=12.7,8.7Hz,1H),1.65–1.53(m,1H).

[0567] Example I-416

[0568] Preparation of Compound I-416

[0569] Step 1: Preparation of compound I-416:

[0570] At 0°C, (1S,3R)-3-aminocyclopentanecarboxylic acid methyl ester hydrochloride (200 mg, 1.11 mmol), dichloromethane (5 mL), and triethylamine (337 mg, 3.33 mmol) were added to a 50 mL single-necked flask and stirred for 20 minutes. A solution of intermediate I-404.1 (210 mg, 0.78 mmol) in dichloromethane (3 mL) was then added dropwise. After the addition was complete, the mixture was stirred at room temperature for 2 hours. After the reaction was complete, the mixture was extracted twice with 30 mL of dichloromethane. The organic phases were combined, washed once with saturated brine, dried over anhydrous sodium sulfate, and the solvent was evaporated under reduced pressure. The intermediate I-416 (white solid, 260 mg) was obtained after purification by column chromatography (petroleum ether / ethyl acetate). 1 H NMR(400MHz,DMSO)δ8.16(d,J=7.8Hz,1H),7.47–7.36(m,3H),6.14(dd,J=17.3,10 .6Hz,1H),5.38(dd,J=17.3,0.6Hz,1H),5.34–5.26(m,1H),4.17–4.04(m,1H),3.88 (d,J=17.7Hz,1H),3.61(s,3H),3.53(d,J=17.8Hz,1H),2.81(p,J=8.3Hz,1H),2.1 0(dt,J=12.7,7.3Hz,1H),1.87–1.76(m,3H),1.75–1.67(m,1H),1.65–1.52(m,1H).

[0571] Example I-452

[0572] Preparation of Compound I-452

[0573] Step 1: Preparation of intermediate I-452.1:

[0574] At room temperature, intermediate II-11-A (2.8 g, 9.2 mmol), oxalyl chloride (1.76 g, 13.8 mmol), dichloromethane (15 mL), and N,N-dimethylformamide (3 drops) were added to a 100 mL single-necked flask. The reaction system was stirred under a nitrogen atmosphere for 30 minutes. After completion of the reaction, the solvent and excess oxalyl chloride were evaporated under reduced pressure to yield intermediate I-452.1 (yellow oil, 2.9 g).

[0575] Step 2: Preparation of intermediate I-452.2:

[0576] Intermediate I-452.2 can be prepared from commercially available (1R,4S)-2-azabicyclo[2.2.1]hept-5-en-3-one (Vince lactam, CAS NO.: 79200-56-9) by the method described in Marco D. Migliore et al.: J. Med. Chem. 2007, 50, 6485-6492.

[0577] 1 H NMR(400MHz,DMSO)δ8.29(s,3H),6.12–6.04(m,1H),5.92–5.84(m,1H),4.24–4.12(m,1H), 3.74–3.67(m,1H),3.66(s,3H),2.56(dt,J=13.9,8.6Hz,1H),1.94(dt,J=13.6,6.7Hz,1H).

[0578] Step 3: Preparation of intermediate I-452.3:

[0579] At 0°C, intermediate I-452.2 (2.4 g, 13.5 mmol), dichloromethane (15 mL), and triethylamine (4.5 g, 45 mmol) were added to a 100 mL single-necked bottle and stirred for 30 min. A solution of intermediate I-452.1 (2.9 g, 9.0 mmol) in dichloromethane (10 mL) was then added dropwise to the system. After the addition was complete, the mixture was stirred at room temperature for 2 h. After the reaction was complete, the mixture was extracted twice with 30 mL of dichloromethane. The organic phases were combined, washed once with saturated brine, dried over anhydrous sodium sulfate, and the solvent was evaporated under reduced pressure. The mixture was purified by column chromatography (petroleum ether / ethyl acetate) to obtain intermediate I-452.3 (light yellow solid, 3.6 g).

[0580] Step 4: Preparation of intermediate I-452.4:

[0581] At room temperature, intermediate I-452.3 (3.6 g, 8.5 mmol), tetrahydrofuran (10 mL), and water (20 mL) were added to a 100 mL single-necked flask and stirred thoroughly. Lithium hydroxide monohydrate (390 mg, 9.3 mmol) was added and allowed to react for 30 min. After the reaction, 1 M hydrochloric acid was added dropwise to adjust the pH to 3-4. Extraction was performed with 30 mL of ethyl acetate. The combined organic phases were washed once with saturated brine, dried over anhydrous sodium sulfate, and the solvent was evaporated under reduced pressure to yield intermediate I-452.4 (white solid, 3.45 g).

[0582] Step 5: Preparation of intermediate I-452.5:

[0583] At room temperature, intermediate I-452.4 (200 mg, 0.49 mmol), oxalyl chloride (93 mg, 0.73 mmol), dichloromethane (4 mL), and N,N-dimethylformamide (2 drops) were added to a 25 mL single-necked flask. The reaction system was stirred under a nitrogen atmosphere for 30 minutes. After completion of the reaction, the solvent and excess oxalyl chloride were evaporated under reduced pressure to yield intermediate I-452.5 (yellow solid, 202 mg).

[0584] Step 6: Preparation of compound I-452:

[0585] At room temperature, tetrahydropyrrole (134 mg, 1.9 mmol), triethylamine (242 mg, 2.4 mmol) and dichloromethane (2 mL) were added to a 25 mL single-necked bottle and stirred thoroughly. A solution of intermediate I-452.5 (202 mg, 0.47 mmol) in dichloromethane (3 mL) was added dropwise to the system and stirred for 2 hours. After the reaction was completed, the solvent was evaporated under reduced pressure and the residue was purified by reverse phase (acetonitrile / water) to obtain I-452 (white solid, 177 mg). 1 H NMR (400MHz, CDCl3) δ7.99(d,J=8.9Hz,1H),7.67(s,1H),7.57(dt,J=9.0,1.9Hz,1H),7.35 (dt,J=8.3,2.0Hz,1H),6.16(dd,J=17.3,10.7Hz,1H),5.95-5.84(m,2H),5.53(d,J=17.2Hz ,1H),5.30(d,J=10.7Hz,1H),5.02(tt,J=8.5,2.4Hz,1H),3.96(d,J=17.1Hz,1H),3.69-3. 59(m,1H),3.58-3.42(m,4H),3.33(d,J=17.1Hz,1H),2.39-2.25(m,1H),2.02-1.82(m,5H).

[0586] Example I-466

[0587] Preparation of Compound I-466

[0588] Step 1: Preparation of intermediate I-466.1:

[0589] At room temperature, intermediate II-13-A (4 g, 12.5 mmol) was dissolved in dichloromethane (25 mL), N,N-dimethylformamide (1 mL) was added, and oxalyl chloride (2.4 g, 18.8 mmol) was added dropwise. The mixture was stirred at room temperature for 1 h to obtain a dichloromethane solution of intermediate I-466.1.

[0590] Step 2: Preparation of intermediate I-466.2:

[0591] At room temperature, 1S,4R(cis)-4-aminocyclopent-2-ene-1-carboxylic acid methyl ester hydrochloride (2.5 g, 13.8 mmol) was suspended in dichloromethane (25 mL). Triethylamine (6.5 g, 63.4 mmol) was added and stirred for 30 min. A dichloromethane solution of the first-stage intermediate I-466.1 was added dropwise under ice bath. The mixture was slowly returned to room temperature while stirring for 40 minutes. After the reaction was completed, water was added to the system, stirred, and allowed to stand for separation. The lower organic phase was separated, the solvent was evaporated under reduced pressure, and the intermediate I-466.2 (yellow oil, 4.5 g) was purified by column chromatography.

[0592] Step 3: Preparation of intermediate I-466.3:

[0593] At room temperature, the intermediate I-466.2 (4.5 g, 9.5 mmol) was dissolved in tetrahydrofuran (20 mL), and an aqueous solution (20 mL) of lithium hydroxide monohydrate (476.4 mg, 11.4 mmol) was added dropwise in an ice bath. The mixture was slowly returned to room temperature while stirring for 50 min. After the reaction was completed, the pH value was adjusted to 1-2 with dilute hydrochloric acid (10%), and a saturated aqueous sodium chloride solution was added. The mixture was extracted with ethyl acetate and purified by column chromatography to obtain the intermediate I-466.3 (colorless oil, 3.6 g). 1 H NMR (400MHz, DMSO) δ12.45 (s, 1H), 8.08 (d, J = 7.9Hz, 1H), 7.66–7.51 (m, 3H), 6. 15(dd,J=17.3,10.7Hz,1H),5.96–5.88(m,1H),5.80–5.76(m,1H),5.39(d,J=17 .3Hz,1H),5.30(d,J=10.6Hz,1H),4.86–4.74(m,1H),3.92(d,J=17.8Hz,1H),3 .58(d,J=17.8Hz,1H),3.49–3.40(m,1H),2.44–2.32(m,1H),1.90–1.77(m,1H).

[0594] Step 4: Preparation of intermediate I-466.4:

[0595] At room temperature, intermediate I-466.3 (220 mg, 0.51 mmol) was dissolved in dichloromethane (5 mL), N,N-dimethylformamide (0.1 mL) was added, and oxalyl chloride (97.8 mg, 0.77 mmol) was added dropwise. The mixture was stirred at room temperature for 1 h to obtain a dichloromethane solution of intermediate I-466.4.

[0596] Step 5: Preparation of compound I-466:

[0597] At room temperature, 2-(aminooxy)propane hydrochloride (114.6 mg, 1.03 mmol) was suspended in dichloromethane (5 mL), triethylamine (260.0 g, 2.57 mmol) was added and stirred for 30 min. A dichloromethane solution of intermediate I-466.4 was added dropwise under ice bath, and the mixture was slowly returned to room temperature while stirring for 40 min. After the reaction was completed, the mixture was washed with water, and the organic phase was evaporated under reduced pressure. The mixture was purified by column chromatography to obtain compound I-466 (white solid, 178 mg). 1 H NMR (400MHz, DMSO) δ10.97 (s, 1H), 8.04 (d, J = 8.4Hz, 1H), 7.67–7.59 (m, 1H), 7.56 (d ,J=7.2Hz,2H),6.18–6.09(m,1H),5.82(s,2H),5.43–5.28(m,2H),4.88–4.78(m,1H) ,4.05–3.94(m,1H),3.89(dd,J=17.8,4.0Hz,1H),3.59(dd,J=17.8,4.0Hz,1H),3.24 (dd,J=8.2,3.7Hz,1H),2.33–2.20(m,1H),1.73–1.63(m,1H),1.12(d,J=6.2Hz,6H).

[0598] Example I-525

[0599] Preparation of Compound I-525

[0600] Step 1: Preparation of intermediate I-525.1:

[0601] Under N2 protection, add intermediate II-69-A (200 mg, 0.55 mmol), dichloromethane (5 mL), and N,N-dimethylformamide (0.2 mL) into a dry single-necked bottle, stir at room temperature to dissolve, add oxalyl chloride (105 mg, 0.83 mmol), and a large amount of bubbles will be generated during the addition. Stir at room temperature for 20 minutes to obtain a dichloromethane solution of intermediate I-525.1.

[0602] Step 2: Preparation of intermediate I-525.2:

[0603] At room temperature, (1S,4R)-4-aminocyclopent-2-ene-1-carboxylic acid methyl ester hydrochloride (146 mg, 0.83 mmol), triethylamine (194 mg, 1.93 mmol), and dichloromethane (5 mL) were added to a 25 mL single-necked flask. The reaction system was stirred thoroughly at room temperature for 20 minutes. A dichloromethane solution of the first-stage intermediate I-525.1 was added dropwise to the system under ice bath and stirred at room temperature for 30 minutes. After the reaction was complete, the solvent was removed under reduced pressure and the product was purified by reverse phase purification to yield compound I-525.2 (oily solid, 200 mg). 1 H NMR (400MHz, DMSO) δ8.63(d,J=7.7Hz,1H),8.12(s,1H),8.08(s,1H),8.04(s,1H),5.93(dt,J=5.6,2.1Hz,1H),5.79(dt,J=5 .6,2.3Hz,1H),4.88–4.80(m,1H),4.34–4.11(m,2H),3.62(s,3H),3.60–3.53(m,1H),2.48–2.40(m,1H),1.98–1.87(m,1H).

[0604] Step 3: Preparation of intermediate I-525.3:

[0605] The intermediate I-525.2 (200 mg, 0.41 mmol), tetrahydrofuran (5 ml) and water (2 ml) were stirred at room temperature for 5 min, and then lithium hydroxide monohydrate (26 mg, 0.62 mmol) was added to the reaction system and stirred at room temperature for 3 h. The reaction was completed after LC-MS monitoring. 1 M hydrochloric acid was added dropwise to the system and the pH was adjusted to 3-4. The mixture was extracted with ethyl acetate, the organic phases were combined, the solvent was evaporated under reduced pressure, and the intermediate I-525.3 (190 mg) was obtained by column chromatography. 1H NMR (400MHz, CDCl3) δ7.89–7.78(m,2H),7.75–7.69(m,1H),7.40(d,J=8.9Hz,1H),6.09–6.03(m,1H),6.00–5.93(m,1H),5.0 8(t,J=8.7Hz,1H),4.03(d,J=18.1Hz,1H),3.79(d,J=18.1Hz,1H),3.62–3.54(m,1H),2.53–2.40(m,1H),2.02–1.92(m,1H).

[0606] Step 4: Preparation of intermediate I-525.4:

[0607] Under N2 protection at room temperature, the intermediate I-525.3 (180 mg, 0.38 mmol), dichloromethane (5 ml), and N,N-dimethylformamide (0.2 mL) were added to a dry single-necked flask and stirred at room temperature to dissolve. Oxalyl chloride (72 mg, 0.57 mmol) was added, and a large amount of bubbles were generated during the addition. Stir at room temperature for 20 minutes to obtain a dichloromethane solution of the intermediate I-525.4.

[0608] Step 5: Preparation of compound I-525:

[0609] At room temperature, (R)-butane-2-ol (42 mg, 0.57 mmol) and dichloromethane (5 mL) were added sequentially to a single-necked flask and stirred thoroughly for 5 minutes. Intermediate I-525.4 was then added dropwise and stirred at room temperature for 30 minutes. After the reaction was complete, the solvent was evaporated under reduced pressure and the product was purified by high-pressure reverse phase chromatography to yield compound I-525 (oily solid, 107 mg). 1 H NMR (400MHz, CDCl3) δ7.85(d,J=1.7Hz,1H),7.80(s,1H),7.72(d,J=1.9Hz,1H),7.40(d,J= 8.8Hz,1H),6.04–5.99(m,1H),5.97–5.89(m,1H),5.07(t,J=8.7Hz,1H),4.93–4.80(m,1H) ,4.05(d,J=18.0Hz,1H),3.79(d,J=18.0Hz,1H),3.54–3.47(m,1H),2.43(dt,J=14.1,8.4H z,1H),1.99–1.91(m,1H),1.70–1.50(m,2H),1.23(d,J=6.3Hz,3H),0.88(t,J=7.4Hz,3H).

[0610] Example I-535

[0611] Preparation of Compound I-535

[0612] Step 1: Preparation of intermediate I-535.1:

[0613] Under N2 protection, intermediate II-30-A (200 mg, 0.69 mmol), dichloromethane (5 mL), and N,N-dimethylformamide (0.2 mL) were added to a dry single-necked bottle and stirred at room temperature to dissolve. Oxalyl chloride (130.4 mg, 1.04 mmol) was added, and a large amount of bubbles were generated during the addition. Stir at room temperature for 20 minutes to obtain a dichloromethane solution of intermediate I-535.1 for later use.

[0614] Step 2: Preparation of compound I-535:

[0615] At room temperature, (1R,4S)-4-aminocyclopent-2-ene-1-carboxylic acid methyl ester hydrochloride (183 mg, 1.03 mmol), triethylamine (244 mg, 2.41 mmol), and dichloromethane (5 mL) were added to a 25 mL single-necked flask. The reaction system was allowed to stand at room temperature and stirred thoroughly for 20 minutes. The temperature was then lowered to 0°C, and intermediate I-535.1 was added dropwise. The reaction was then returned to room temperature and stirred for 30 minutes. After the reaction was complete, the solvent was evaporated under reduced pressure, and the product was purified by high-pressure reverse phase chromatography to yield compound I-535 (oily solid, 200 mg). 1 H NMR (400MHz, CDCl3) δ7.67(s,1H),7.60–7.54(m,1H),7.41–7.36(m,1H),7.21(d,J=8.9Hz,1H),5.97–5.92(m,1H),5.84–5.77(m,1H),5.06–4. 97(m,1H),3.84(d,J=17.3Hz,1H),3.76(s,3H),3.58–3.50(m,1H),3.2 2(d,J=17.3Hz,1H),2.59–2.48(m,1H),2.00–1.92(m,1H),1.75(s,3H).

[0616] The preparation was carried out similarly to the preparation examples given above, and the analytical data of some of the example compounds are shown in the table below.

[0617] Table C

[0618] Table D

[0619] In analogy to the preparation examples described and mentioned above, and taking into account the general details relating to the preparation of substituted isoxazolinecarboxamides, the compounds described below are obtained:

[0620] Table 2.1: Compounds 2.1-1 to 2.1-574 of the general formula (I.1) according to the invention,

[0621] wherein Z and G are as defined below.

[0622] Table 2.1

[0623] Table 2.2: Compounds 2.2-1 to 2.2-574 of the general formula (I.2) according to the invention,

[0624] Where Z and G correspond to those defined in Table 2.1.

[0625] Table 2.3: Compounds 2.3-1 to 2.3-574 of the general formula (I.3) according to the invention,

[0626] Where Z and G correspond to those defined in Table 2.1.

[0627] Table 2.4: Compounds 2.4-1 to 2.4-574 of the general formula (I.4) according to the invention,

[0628] Where Z and G correspond to those defined in Table 2.1.

[0629] Table 2.5: Compounds 2.5-1 to 2.5-574 of the general formula (I.5) according to the invention,

[0630] Where Z and G correspond to those defined in Table 2.1.

[0631] Table 2.6: Compounds 2.6-1 to 2.6-574 of the general formula (I.6) according to the invention,

[0632] Where Z and G correspond to those defined in Table 2.1.

[0633] Table 2.7: Compounds 2.7-1 to 2.7-574 of the general formula (I.7) according to the invention,

[0634] Where Z and G correspond to those defined in Table 2.1.

[0635] Table 2.8: Compounds 2.8-1 to 2.8-574 of the general formula (I.8) according to the invention,

[0636] Where Z and G correspond to those defined in Table 2.1.

[0637] Table 2.9: Compounds 2.9-1 to 2.9-574 of the general formula (I.9) according to the invention,

[0638] Where Z and G correspond to those defined in Table 2.1.

[0639] Table 2.10: Compounds 2.10-1 to 2.10-574 of the general formula (I.10) according to the invention,

[0640] Where Z and G correspond to those defined in Table 2.1.

[0641] Table 2.11: Compounds 2.11-1 to 2.11-574 of the general formula (I.11) according to the invention,

[0642] Where Z and G correspond to those defined in Table 2.1.

[0643] Table 2.12: Compounds 2.12-1 to 2.12-574 of the general formula (I.12) according to the invention,

[0644] Where Z and G correspond to those defined in Table 2.1.

[0645] Table 2.13: Compounds 2.13-1 to 2.13-574 of the general formula (I.13) according to the invention,

[0646] Where Z and G correspond to those defined in Table 2.1.

[0647] Table 2.14: Compounds 2.14-1 to 2.14-574 of the general formula (I.14) according to the invention,

[0648] Where Z and G correspond to those defined in Table 2.1.

[0649] Table 2.15: Compounds 2.15-1 to 2.15-574 of the general formula (I.15) according to the invention,

[0650] Where Z and G correspond to those defined in Table 2.1.

[0651] Table 2.16: Compounds 2.16-1 to 2.16-574 of the general formula (I.16) according to the invention,

[0652] Where Z and G correspond to those defined in Table 2.1.

[0653] Table 2.17: Compounds 2.17-1 to 2.17-574 of the general formula (I.17) according to the invention,

[0654] Where Z and G correspond to those defined in Table 2.1.

[0655] Table 2.18: Compounds 2.18-1 to 2.18-574 of the general formula (I.18) according to the invention,

[0656] Where Z and G correspond to those defined in Table 2.1.

[0657] Table 2.19: Compounds 2.19-1 to 2.19-574 of the general formula (I.19) according to the invention,

[0658] Where Z and G correspond to those defined in Table 2.1.

[0659] Similarly, the structures of general formula (I.20) to general formula (I.179) are shown in Table 3. In the specific compounds corresponding to each general formula, Z and G are defined as in Table 2.1 (corresponding to their numbers "-1" to "-574").

[0660] Table 3

[0661] The following control compounds can be prepared by methods similar to the preparation examples given above or with reference to WO2018228985A1, WO2019145245A1, and WO2019034602A1.

[0662] Biological Example 1: Indoor herbicidal activity assay

[0663] The herbicidal activity test method of the compounds of the present invention is as follows:

[0664] Before seedlings: Sow a certain amount of grass weeds (barnyard grass, goosegrass, crabgrass, Japanese alopecuroides, sedge grass, sedge grass, ryegrass, bluegrass, aesculus fragrans, wild oats, big-spiked alopecuroides, Japanese alopecuroides, alopecuroides), broadleaf weeds (chicken intestine, amaranth, wild rape, chickweed, veronica, schizonepeta, wild arrowhead, cyperus) and Cyperus rotundus seeds in a 7 cm diameter container with holes at the bottom filled with nutrient soil (sandy soil). The seeds were placed in plastic pots with a pH of 6.1 and 1% organic matter. After sowing, the soil was covered with an appropriate amount of soil and then soaked with water by bottom absorption. The seeds were placed in a constant temperature and light culture room and then incubated for 24 hours before soil spraying. The spraying was carried out using a 3WP-2000 walking spray tower produced by the Nanjing Agricultural Mechanization Research Institute of the Ministry of Agriculture. The main shaft speed was 96 mm / r, the spray height was 300 mm, the effective spray width of the nozzle was 350 mm, and the spray area was 0.35 m. 2 , nozzle flow rate 390mL / min;

[0665] Post-emergence: Appropriate amounts of grass weeds (barnyardgrass, goosegrass, crabgrass, Japanese alopecuroides, sedgegrass, lycopodiella, schizonepeta ...

[0666] Grading standards for pest control effects:

[0667] A indicates that the fresh weight inhibition rate is greater than or equal to 80% to 100%;

[0668] B indicates that the fresh weight inhibition rate is greater than or equal to 60% and less than 80%;

[0669] C indicates that the fresh weight inhibition rate is greater than or equal to 40% and less than 60%;

[0670] D indicates that the fresh weight inhibition rate is greater than or equal to 20% and less than 40%;

[0671] E means that the fresh weight inhibition rate is less than 20%.

[0672] According to the above test method, some compounds of general formula (I) and control compounds were selected for parallel testing of herbicidal activity. The results are shown in Tables 4-1 to 4-5:

[0673] Table 4-1: Herbicidal activity of some compounds of formula (I) (pre-emergence)

[0674] “-” means not tested

[0675] Table 4-2: Herbicidal activity of some compounds of formula (I) and control compounds (30 g ai / ha, post-emergence)

[0676] “-” means not tested

[0677] Table 4-3: Herbicidal activity of some compounds of formula (I) and control compounds (60 g ai / ha, post-emergence)

[0678] “-” means not tested

[0679] Table 4-4: Herbicidal activity of some compounds of formula (I) and control compounds (60 g ai / ha, pre-emergence)

[0680] “-” means not tested

[0681] Table 4-5: Herbicidal activity of some compounds of formula (I) and control compounds (120 g ai / ha, pre-emergence)

[0682] “-” means not tested

[0683] Biological Example 2: Field Herbicidal Activity Assay

[0684] The compounds (I) according to the present invention are applied to vacant vineyard land for controlling undesirable vegetation.

[0685] The experimental plot was flat and had medium loam soil. The main weeds in the field included goosegrass, barnyard grass, crabgrass, water peanut, and small sedge. The weeds were sprayed before emergence using a fan-shaped sprayer designed for herbicides at a water rate of 450 L / ha. Each treatment plot had an area of ​​20 m 2 According to the set dosage, the amount of compound (I) required for each cell was weighed, and the compound (I) was prepared into a corresponding volume of liquid by the secondary dilution method.

[0686] The plant control efficacy of compound (I) on weeds was investigated 15 days after application, and the final plant control efficacy and fresh weight control efficacy of compound (I) on weeds were investigated 30 days after application.

[0687] Weed control effect (fresh weight) = (number of weeds in the control area (fresh weight) - number of weeds in the treatment area (fresh weight)) / number of weeds in the control area (fresh weight) × 100

[0688] The results showed that the compounds of the present invention generally have good weed control effects and can produce good weed control effects even at lower application doses.

[0689] The above description is only a preferred embodiment of the present invention. It should be pointed out that for ordinary technicians in this field, several changes and improvements can be made without departing from the creative concept of the present invention, which all fall within the scope of protection of the present invention.

Claims

1. A 3-phenylisoxazoline-5-carboxamide compound as shown in formula (I), its stereoisomers and agriculturally acceptable salts thereof: 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 Represents C1-C 12 -alkyl, C3-C7-cycloalkyl, C3-C7-cycloalkyl-C1-C8-alkyl, C2-C8-alkenyl, C2-C8-alkynyl, C5-C6-cycloalkenyl, -N=(C1-C6-cycloalkyl), -N=C(C1-C5-alkyl)2, phenyl, C1-C4-alkyl-phenyl, aromatic heterocyclic group or C1-C4-alkyl-aromatic heterocyclic group, each of which is optionally substituted by m3 units selected from halogen, -CN, -OH, C1-C6-alkoxy, C1-C6-alkoxycarbonyl, aromatic heterocyclic group, aryl and -S(O) n Group substitution of R2; R4 and R5 independently represent H, -OH, C1-C 12 -alkyl, C1-C3-alkoxy, C1-C6-alkoxy-C1-C3-alkyl, C1-C6-alkoxycarbonyl-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 a saturated or partially unsaturated or fully unsaturated five-, six- or seven-membered ring which, in addition to the nitrogen atom, may also contain r carbon atoms, o oxygen atoms and may be optionally substituted by m4 groups selected from halogen, C1-C6 alkyl, halo-C1-C6 alkyl, oxo, -CO2R6; R6 represents H, or represents C1-C8-alkyl, C3-C6-cycloalkyl, C3-C8-alkenyl or C3-C8-alkynyl, each of which is optionally substituted by m5 groups selected from halogen, -CN and C1-C2-alkoxy; When Z is selected from Z-1 to Z-4, wherein Z-1 to Z-4 have the following meanings: Then X3 represents H, F, Cl, Br or I, X1 and X2 each independently represent H, F, Cl, Br, I, -OH, -CN, -NO2, -S(O) 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; When Z is selected from Z-5 to Z-7, wherein Z-5 to Z-7 have the following meanings: Then X3 represents H or F, X1 represents F, Cl, Br, I, -CH3, -CN, -NO2, -S(O) n R2 or -OS(O) n R2, X2 represents -CF3, -CF2H, -OCF3, -OCF2H or -OCFH2; R2 represents C1-C4-alkyl or C3-C4-cycloalkyl, each of which is substituted by m2 groups selected from F and Cl; wherein the arrows respectively represent the bonds toward the group CO-G of formula (I); m1 is 0, 1, 2, or 3; m2 is 0, 1, 2 or 3; m3 is 0, 1, 2, 3, 4, 5, 6, 7 or 8; m4 is 0, 1, 2, 3, 4, or 5; m5 is 0, 1, 2, 3, 4 or 5; m6 is 0, 1, 2, or 3; n is 0, 1 or 2; o is 0, 1, or 2; r is 3, 4, 5 or 6.

2. The compound of formula (I) according to claim 1, its stereoisomers and agriculturally acceptable salts thereof: in, R1 represents C1-C3-alkyl, C3-C4-cycloalkyl, C2-C3-alkenyl, C2-C3-alkynyl or C1-C3-alkoxy, each of which is substituted by m1 groups selected from the group consisting of halogen, -CN, -OH and C1-C2-alkoxy; G represents -OR3 or -NR4R5; R3 represents H, or Represents 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 group, C1-C3-alkyl-aromatic heterocyclic group or C2-C6-alkynyl, each of which is substituted by m3 groups selected from the group consisting of 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, in addition to the nitrogen atom, may also contain r carbon atoms, o oxygen atoms and may be optionally substituted by m4 groups selected from halogen, C1-C6-alkyl, halogen-C1-C6-alkyl, oxo, -CO2R6; R2 represents a C1-C4-alkyl group; R6 represents H, or represents C1-C6-alkyl, C3-C6-cycloalkyl, C3-C8-alkenyl or C3-C8-alkynyl, each of which is optionally substituted by m5 groups selected from halogen, -CN and C1-C2-alkoxy; m1 is 0, 1, 2, or 3; m3 is 0, 1, 2, 3, 4, 5, 6, 7 or 8; m4 is 0, 1, 2, 3, or 4; m5 is 0, 1, 2 or 3; n is 0, 1 or 2; o is 0, 1, or 2; r is 3, 4 or 5.

3. The compound of formula (I) according to claim 2, its stereoisomers and agriculturally acceptable salts thereof: in, R1 represents C1-C3-alkyl, C2-C3-alkenyl, C2-C3-alkynyl or C1-C3-alkoxy, 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-alkynyl, C1-C3-alkoxy-C1-C3-alkyl, -N=C(C1-C3-alkyl)2, phenyl, C1-C3-alkyl-phenyl, aromatic heterocyclic group, C1-C3-alkyl-aromatic heterocyclic group, phenyl-C1-C3-alkyl or aromatic heterocyclic group-C1-C3-alkyl, each of which is substituted by m3 groups selected from the group consisting of F, Cl, Br, I, -CN, -OH, -OCH3 or -S(O) n R2; R4, R5 independently represent H, -OH, C1-C6-alkyl, C1-C3-alkoxy or -S(O) n R2; or R4 and R5 together with the nitrogen atom to which they are attached form a saturated five-membered or six-membered ring which contains 4 or 5 carbon atoms in addition to the nitrogen atom; R2 represents a C1-C3-alkyl group; m1 is 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 agriculturally acceptable salts thereof: 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; or 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 to which they are attached form a saturated five-membered ring or six-membered ring which contains 4 or 5 carbon atoms in addition to the nitrogen atom.

5. The compound of formula (I) according to claim 1, its stereoisomers and agriculturally acceptable salts thereof: in, Z stands for Z-1; 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, each of which is substituted by m6 groups selected from F, Cl and Br; m6 is 0, 1, 2, or 3.

6. The compound of formula (I) according to claim 5, its stereoisomers and agriculturally acceptable salts thereof: in, Z stands for Z-1; X3 represents H or F; X1 and X2 each independently represent H, F, Cl, Br, -CH3, -CN, -OCH3, -CF3, -CF2H, -OCF3 or -OCF2H.

7. The compound of formula (I) according to claim 1, its stereoisomers and agriculturally acceptable salts thereof: Z stands for Z-5 or Z-7; X3 represents H; X1 represents F, Cl or Br; X2 represents -CF3, -CF2H, -OCF3 or -OCF2H.

8. A method for preparing the compound of formula (I), its stereoisomers and agriculturally acceptable salts thereof as claimed in any one of claims 1 to 7, characterized in that: The method comprises the following steps: (1) condensing the compound represented by the general formula (V) with hydroxylamine or a hydroxylamine salt to form a compound represented by the general formula (IV); (2) The compound represented by the general formula (IV) is reacted with a chlorinating agent to generate a compound represented by the general formula (III); (3) The compound represented by the general formula (III) and the compound represented by the general formula (VII) are cyclized under the action of a base or chiral catalyst to obtain the compound represented by the general formula (II) directly or through hydrolysis; (4) reacting the compound represented by the general formula (II) with the compound represented by the general formula (VI) to obtain a 3-phenylisoxazoline-5-carboxamide compound represented by the general formula (I); Where R7 represents H, or represents 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 1-7.

9. A herbicidal composition, characterized in that: It comprises at least one of the compound of formula (I), its stereoisomer or salt thereof as claimed in any one of claims 1 to 7, wherein the compound of formula (I) is used as an active component, and the weight percentage of the active component in the composition is 0.1-99.9%.

10. The herbicidal composition according to claim 9 further comprising a formulation adjuvant.

11. The herbicidal composition according to claim 9, comprising at least one further active compound selected from the group consisting of insecticides, acaricides, herbicides, fungicides, safeners and / or growth regulators.

12. The herbicidal composition according to claim 9, comprising a safener.

13. The herbicidal composition according to claim 12, wherein the safener is selected from mefenpyr-butyl, cyproconazole, isoxadiazole, cloquintocet-mexyl, fenthiocarb, fenthiocarb, dichloropropane or Metcamifen.

14. A method for controlling harmful plants, characterized in that: An effective amount of at least one compound of the formula (I) as claimed in any one of claims 1 to 7 or a herbicidal composition as claimed in any one of claims 9 to 13 is applied to the plants or the locus where the harmful plants grow.

15. Use of a compound of formula (I) according to any one of claims 1 to 7 or a herbicidal composition according to any one of claims 9 to 13 for controlling harmful plants.

16. The use according to claim 15, characterized in that The compounds of the formula (I) or herbicidal compositions comprising them are used for controlling harmful plants in crops of useful plants.

17. The use according to claim 16, wherein the useful plant crop is a transgenic crop or a crop treated with genome editing technology.

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