A tetra-substituted benzoic acid ester compound containing an alkoxy acetic acid ester substituent and application thereof

Abstract

The application discloses a tetra-substituted benzoate compound containing an alkoxyacetic ester substituent and an application thereof, and has a structure as shown in a formula I. Each substituent in the formula I compound is defined in the specification. The formula I compound has excellent herbicidal activity and crop safety, and can be used for preventing and treating agricultural weeds.

Description

TECHNICAL FIELD

[0001] The present application belongs to the field of herbicides, and particularly relates to a tetra-substituted benzoate compound containing an alkoxyacetic acid ester substituent and application thereof. BACKGROUND

[0002] Weeds cause huge economic losses to the world by reducing the yield and quality of crops. In the world, crops have to fight against hundreds of weeds. Due to the succession, change of weed populations, and the generation and rapid development of resistance to chemical pesticides, and the increasing awareness of people on the pollution problems of chemical pesticides and the protection of ecological environment, there is still a need to research and develop more effective and / or more selective herbicides.

[0003] Patents EP83055A2 and WO2016120116A1 respectively disclose tetra-substituted benzene compounds with alkoxyacetic acid ester substituents and their use as herbicides, and specifically disclose that compounds KC1 (the 57th compound in Table 1 in the patent specification of patent EP83055A2) and KC2 (the compound in Example 1 in the patent specification of patent WO2016120116A1) have high herbicidal activity. However, the herbicidal activity and / or safety to crops of these compounds are not completely satisfactory.

[0004]

[0005] With the gradual reduction of arable land in the world, the continuous growth of population and the increasing demand for food, it is also necessary for people to rapidly develop agricultural production technology, improve and perfect the farming system, and continuously invent new and improved herbicidal compounds and compositions. SUMMARY

[0006] The purpose of the present application is to provide a tetra-substituted benzoate compound containing an alkoxyacetic acid ester substituent with a novel structure, and a herbicidal composition with the compound as an active ingredient. The compound has the characteristics of excellent herbicidal activity at a lower application dose, and high safety to crops at a higher application dose. The purpose of the present application can also extend to provide a new compound for use as a desiccant or defoliant.

[0007] The technical solutions adopted by the present application are as follows:

[0008] The present application provides a novel tetra-substituted benzoate compound containing an alkoxyacetic acid ester substituent, which has a structure as shown in formula I:

[0009]

[0010] wherein,

[0011] X is selected from hydrogen, halogen, C1-C6alkyl or C1-C6alkoxy;

[0012] Y is selected from halogen, cyano, nitro, C1-C6alkyl, C1-C6alkoxy, CONH2or CSNH2;

[0013] R and Ak are each independently selected from C1-C6alkyl, C2-C8alkenyl, C2-C8alkynyl, C3-C8cycloalkyl, C1-C6haloalkyl, C1-C6alkoxyC1-C6alkyl, C1-C6alkylthioC1-C6alkyl, C1-C6alkylaminoC1-C6alkyl, C3-C8cycloalkylC1-C6alkyl, C2-C8oxacycloalkylC1-C6alkyl, C1-C6alkoxycarbonylC1-C6alkyl, phenyl or benzyl, and the aforementioned groups can be further substituted with any combination of one to multiple halogen, cyano, nitro, C1-C6alkoxy, C1-C6haloalkyl or C1-C6haloalkoxy, or R and Ak together with the atoms to which they are attached form a 5- to 7-membered heterocyclic ring;

[0014] Het is selected from a 3- to 7-membered monocyclic or 6- to 10-membered bicyclic ring system, each ring system containing ring members selected from carbon atoms and 0 to 5 heteroatoms independently selected from up to 2 O atoms, up to 2 S atoms and up to 5 N atoms, each ring system optionally substituted with up to 5 substituents independently selected from halogen, cyano, amino, hydroxy, nitro, mercapto, C1-C6alkyl, C2-C8alkenyl, C2-C8alkynyl, C3-C8cycloalkyl, C1-C6haloalkyl, C1-C6alkoxy, C1-C6alkylamino, C1-C6alkylthio, C1-C6alkylsulfinyl, C1-C6alkylsulfonyl, C1-C6alkoxyC1-C6alkyl, C3-C8cycloalkylC1-C6alkyl, phenyl or benzyl, and the aforementioned groups can be further substituted with any combination of one to multiple halogen, cyano, nitro, C1-C6alkoxy, C1-C6alkylamino or C1-C6alkylthio.

[0015] More preferred compounds of the present application are those of formula I wherein:

[0016] X is selected from hydrogen or halogen;

[0017] Y is selected from halogen, cyano, nitro, CONH2or CSNH2;

[0018] R and Ak are each independently selected from the group consisting of C1-C6alkyl, C2-C8alkenyl, C2-C8alkynyl, C3-C8cycloalkyl, C1-C6haloalkyl, C1-C6alkoxyC1-C6alkyl, C1-C6alkylthioC1-C6alkyl, C1-C6alkylaminoC1-C6alkyl, C3-C8cycloalkylC1-C6alkyl, C2-C8oxacycloalkylC1-C6alkyl, C1-C6alkoxycarbonylC1-C6alkyl, phenyl or benzyl, and the aforementioned groups can be further substituted by any combination of one to five halogen, cyano, nitro, C1-C6alkoxy, C1-C6haloalkyl or C1-C6haloalkoxy;

[0019] Het is selected from a 5- or 6-membered monocyclic ring or an 8- to 10-membered bicyclic ring, each ring having ring members selected from carbon atoms and 0 to 5 heteroatoms independently selected from up to 2 O atoms, up to 2 S atoms and up to 5 N atoms, each ring being optionally substituted with up to 5 substituents independently selected from halogen, cyano, amino, hydroxy, nitro, mercapto, C1-C6alkyl, C2-C8alkenyl, C2-C8alkynyl, C3-C8cycloalkyl, C1-C6haloalkyl, C1-C6alkoxy, C1-C6alkylamino, C1-C6alkylthio, C1-C6alkylsulfinyl, C1-C6alkylsulfonyl, C1-C6alkoxyC1-C6alkyl, C3-C8cycloalkylC1-C6alkyl, phenyl or benzyl, and the aforementioned groups can be further substituted by any combination of one to five halogen, cyano, nitro, C1-C6alkoxy, C1-C6alkylamino or C1-C6alkylthio.

[0020] Preferred compounds of the present application are those in which in formula I:

[0021] X is selected from hydrogen, fluorine or chlorine;

[0022] Y is selected from fluorine, chlorine, bromine or cyano;

[0023] R and Ak are each independently selected from the group consisting of C1-C6alkyl, C2-C8alkenyl, C2-C8alkynyl, C3-C8cycloalkyl, C1-C6haloalkyl, C1-C6alkoxyC1-C6alkyl, C1-C6alkylthioC1-C6alkyl, C1-C6alkylaminoC1-C6alkyl, C3-C8cycloalkylC1-C6alkyl, C2-C8oxacycloalkylC1-C6alkyl, C1-C6alkoxycarbonylC1-C6alkyl, phenyl or benzyl, and the aforementioned groups can be further substituted by any combination of one to five halogen, cyano, nitro, C1-C6alkoxy, C1-C6haloalkyl or C1-C6haloalkoxy;

[0024] Het is selected from

[0025]

[0026] wherein

[0027] W1, W2and W3are each independently oxygen or sulfur;

[0028] R1and R2are each independently selected from hydrogen, cyano, amino, C1-C6alkyl, C1-C6haloalkyl, C1-C6haloalkoxy, C3-C7cycloalkyl, C2-C6alkenyl, C2-C6haloalkenyl, C2-C6alkynyl, benzyl, C1-C6cyanoalkyl, OR7, or R1and R2together with the atoms to which they are attached form a 3- to 7-membered ring system, and the ring system can be further substituted with any combination of one to more halogen, nitro, cyano, C1-C4alkyl, C1-C4alkoxy, C1-C4alkylamino or C1-C4alkylthio;

[0029] R3and R4are each independently selected from hydrogen, C1-C6alkyl, C1-C6haloalkyl, C1-C6haloalkoxy, C3-C7cycloalkyl, C2-C6alkenyl, C2-C6haloalkenyl, C2-C6alkynyl, OR7, S(O)nR7, NR7R8, or R3and R4together with the atoms to which they are attached form a 3- to 7-membered ring system, and the ring system can be further substituted with any combination of one to more halogen, nitro, cyano, C1-C4alkyl, C1-C4alkoxy, C1-C4alkylamino or C1-C4alkylthio, wherein n is 0, 1 or 2; n R3and R4are each independently selected from hydrogen, C1-C6alkyl, C1-C6haloalkyl, C1-C6haloalkoxy, C3-C7cycloalkyl, C2-C6alkenyl, C2-C6haloalkenyl, C2-C6alkynyl, OR7, S(O)nR7, NR7R8, or R3and R4together with the atoms to which they are attached form a 3- to 7-membered ring system, and the ring system can be further substituted with any combination of one to more halogen, nitro, cyano, C1-C4alkyl, C1-C4alkoxy, C1-C4alkylamino or C1-C4alkylthio, wherein n is 0, 1 or 2;

[0030] R5is selected from hydrogen, halogen or C1-C6alkyl;

[0031] R6is selected from hydrogen, halogen, C1-C6alkyl, OR7, SR7, S(O)nR7, NR7R8, or R6and R5together with the atoms to which they are attached form a 3- to 7-membered ring system, and the ring system can be further substituted with any combination of one to more halogen, nitro, cyano, C1-C4alkyl, C1-C4alkoxy, C1-C4alkylamino or C1-C4alkylthio, wherein n is 0, 1 or 2; n R7, OSO2R7or NR7R8;

[0032] R7and R8are each independently selected from hydrogen, C1-C6alkyl, C1-C6haloalkyl, C3-C7cycloalkyl, C2-C6alkenyl, C2-C6haloalkenyl, C2-C6alkynyl, phenyl or benzyl, and the aforementioned groups can be further substituted with any combination of one to more halogen, nitro, cyano, C1-C4alkyl, C1-C4alkoxy, C1-C4alkylamino or C1-C4alkylthio.

[0033] A is selected from N or CR5;

[0034] More preferred compounds of the present application are those of formula I wherein:

[0035] X is selected from hydrogen, fluorine or chlorine;

[0036] Y is selected from fluorine, chlorine, bromine or cyano;

[0037] R and Ak are each independently selected from C1-C6alkyl, C2-C8alkenyl, C2-C8alkynyl, C3-C8cycloalkyl, C1-C6haloalkyl, C1-C6alkoxyC1-C6alkyl, C1-C6alkylthioC1-C6alkyl, C1-C6alkylaminoC1-C6alkyl, C3-C8cycloalkylC1-C6alkyl, C2-C8oxacycloalkylC1-C6alkyl, C1-C6alkoxycarbonylC1-C6alkyl, phenyl or benzyl, and the aforementioned groups can be further substituted by any combination of one to more halogen, cyano, nitro, C1-C6alkoxy, C1-C6haloalkyl or C1-C6haloalkoxy;

[0038] Het is selected from Het1, Het2, Het3, Het4, Het6, Het8, Het 10 , Het 11 , Het 12 or Het 14 .

[0039] More preferred compounds according to the application are those of formula I wherein:

[0040] X is selected from hydrogen, fluorine or chlorine;

[0041] Y is selected from fluorine or chlorine;

[0042] Ak is selected from methyl, ethyl, n-propyl, i-propyl, phenyl or 2,4-dichlorophenyl;

[0043] R is selected from methyl, ethyl, n-propyl, i-propyl, n-butyl, i-butyl, n-pentyl, i-pentyl, n-hexyl, allyl, 2-buten-1-yl, propargyl, 2-butyn-1-yl, cyclopropyl, cyclopentyl, trifluoromethyl, 2-fluoroethyl, 2,2,2-trifluoroethyl, 2-chloroethyl, 3-chloro-n-propyl, 4-chloro-n-butyl, methoxymethyl, ethoxymethyl, 2-methoxyethyl, 2-ethoxyethyl, methylthiomethyl, 2-methylthioethyl, cyclopropylmethyl, 2-cyclopropylethyl, cyclobutylmethyl, cyclopentylmethyl, cyclohexylmethyl, oxacyclopropanylmethyl, tetrahydrofuran-2-methyl, tetrahydrofuran-3-methyl, 2,2-dimethyl-1,3-dioxolan-4-methyl, methoxycarbonylmethyl, ethoxycarbonylmethyl, 1-ethoxycarbonylethyl, 2-ethoxycarbonylethyl, cyanomethyl, 2-nitroethyl, 2-(2-methoxyethoxy)ethyl, 2-(trifluoroethoxy)ethyl, 2-(2-chloroethoxy)ethyl, 2-(cyanomethoxy)ethyl and the like;

[0044] Het is selected from Het1or Het3, wherein R1and R2together with the atoms to which they are attached form a 6-membered ring system, W1and W2are selected from oxygen; Het is selected from Het6, wherein R1, R2are selected from methyl, W1and W2are selected from oxygen, W3is selected from sulfur; Het is selected from Het8, wherein R1is selected from methyl, R3is selected from trifluoromethyl, R4is selected from hydrogen, W1and W2are selected from oxygen; Het is selected from Het 10 Het is selected from Het9, wherein R3is selected from trifluoromethyl, R4and R6are selected from hydrogen or methyl, W1is selected from oxygen; Het is selected from Het 11 Het is selected from Het10, wherein R1, R4are selected from hydrogen, R3is selected from trifluoromethyl, R6is selected from chloro, A is selected from nitrogen; Het is selected from Het 12 Het is selected from Het11, wherein R3and R4together with the atoms to which they are attached form a 6-membered ring system, W1and W2are selected from oxygen; Het is selected from Het 14 Het is selected from Het12, wherein R6is selected from tert-butyl, W1is selected from oxygen.

[0045] Particularly preferred compounds of the present application are tetra-substituted benzoate compounds containing an alkoxy acetic acid ester substituent as described in Formula I, selected from any one of the following compounds:

[0046] 2-chloro-4-fluoro-5-(1,3-dioxo-hexahydro-imidazo[1,5-a]pyridin-2(3H)-yl)benzoic acid (1 -methoxy-1 -ethoxycarbonylmethyl) ester (Compound 1-2);

[0047] 2-chloro-4-fluoro-5-(1,3-dioxotetrahydro-1 H-[1,2,4]triazolo[1,2-a]pyridazin-2(3H)-yl)benzoic acid (1 -methoxy-1 -methoxycarbonylmethyl) ester (Compound 2-1 );

[0048] 2-chloro-4-fluoro-5-(1,3-dioxotetrahydro-1 H-[1,2,4]triazolo[1,2-a]pyridazin-2(3H)-yl)benzoic acid (1 -ethoxy-1 -ethoxycarbonylmethyl) ester (Compound 2-27);

[0049] 2-chloro-5-(1,3-dioxooctahydro-2H-isoindol-2-yl)benzoic acid (1 -methoxy-1 -methoxycarbonylmethyl) ester (Compound 3-1 );

[0050] 2-chloro-5-(1,3-dioxooctahydro-2H-isoindol-2-yl)benzoic acid (1 -methoxy-1 -isopentoxycarbonylmethyl) ester (Compound 3-7);

[0051] 2-chloro-5-(1,3-dioxooctahydro-2H-isoindol-2-yl)benzoic acid (1 -ethoxy-1 -ethoxycarbonylmethyl) ester (Compound 3-27);

[0052] 2-chloro-5-(1,3-dioxo-octahydro-2H-isoindol-2-yl)benzoic acid (1 -ethoxy-1 - isopropoxycarbonylmethyl) ester (compound 3-129);

[0053] 2-chloro-4-fluoro-5-(1,3-dioxo-octahydro-2H-isoindol-2-yl)benzoic acid (1 - ethoxy-1 -isopropoxycarbonylmethyl) ester (compound 3-129);

[0054] 2-chloro-4-fluoro-5-(1,3-dioxo-octahydro-2H-isoindol-2-yl)benzoic acid (1 - ethoxy-1 -isopropoxycarbonylmethyl) ester (compound 3-129);

[0055] 2-chloro-4-fluoro-5-(1,3-dioxo-octahydro-2H-isoindol-2-yl)benzoic acid (1 - ethoxy-1 -isopropoxycarbonylmethyl) ester (compound 3-129);

[0056] 2-chloro-4-fluoro-5-(1,3-dioxo-octahydro-2H-isoindol-2-yl)benzoic acid (1 - ethoxy-1 -isopropoxycarbonylmethyl) ester (compound 3-129);

[0057] 2-chloro-4-fluoro-5-(5-tert-butyl-2-oxo-1,3,4-oxadiazol-3(2H)-yl)benzoic acid (1 - methoxy-1 -n-pentoxycarbonylmethyl) ester (compound 4-6);

[0058] 2-chloro-4-fluoro-5-(5-tert-butyl-2-oxo-1,3,4-oxadiazol-3(2H)-yl)benzoic acid (1 - methoxy-1 -n-pentoxycarbonylmethyl) ester (compound 4-6);

[0059] 2-chloro-5-(3,5-dimethyl-2,6-oxo-4-thioxo-1,3,5-triazin-1 -yl)benzoic acid (1 - ethoxy-1 -isopropoxycarbonylmethyl) ester (compound 5-29);

[0060] 2-chloro-4-fluoro-5-(3,5-dimethyl-2,6-oxo-4-thioxo-1,3,5-triazin-1 -yl)benzoic acid (1 - methoxy-1 -n-pentoxycarbonylmethyl) ester (compound 4-6);

[0061] 2-chloro-4-fluoro-5-(3,5-dimethyl-2,6-oxo-4-thioxo-1,3,5-triazin-1 -yl)benzoic acid (1 - methoxy-1 -n-pentoxycarbonylmethyl) ester (compound 4-6);

[0062] 2-Chloro-4-fluoro-5-(3-methyl-2,6-dioxo-4-trifluoromethyl-3,6-dihydropyrimidin- 1 (2H)-yl)benzoic acid (1 -methoxy- 1 -cyclopropylmethoxycarbonylmethyl) ester (Compound 6-68);

[0063] 2-Chloro-4-fluoro-5-(3-methyl-2,6-dioxo-4-trifluoromethyl-3,6-dihydropyrimidin- 1 (2H)-yl)benzoic acid (1 -methoxy- 1 -cyclopropylmethoxycarbonylmethyl) ester (Compound 6-68);

[0064] 2-Chloro-4-fluoro-5-(3-methyl-2,6-dioxo-4-trifluoromethyl-3,6-dihydropyrimidin- 1 (2H)-yl)benzoic acid (1 -methoxy- 1 -cyclopropylmethoxycarbonylmethyl) ester (Compound 6-68);

[0065] 2-Chloro-4-fluoro-5-(3-methyl-2,6-dioxo-4-trifluoromethyl-3,6-dihydropyrimidin- 1 (2H)-yl)benzoic acid (1 -methoxy- 1 -cyclopropylmethoxycarbonylmethyl) ester (Compound 6-68);

[0066] 2-Chloro-4-fluoro-5-(3-methyl-2,6-dioxo-4-trifluoromethyl-3,6-dihydropyrimidin- 1 (2H)-yl)benzoic acid (1 -methoxy- 1 -cyclopropylmethoxycarbonylmethyl) ester (Compound 6-68);

[0067] 2-Chloro-4-fluoro-5-(3-methyl-2,6-dioxo-4-trifluoromethyl-3,6-dihydropyrimidin- 1 (2H)-yl)benzoic acid (1 -methoxy- 1 -cyclopropylmethoxycarbonylmethyl) ester (Compound 6-68);

[0068] 2-Chloro-4-fluoro-5-(3-methyl-2,6-dioxo-4-trifluoromethyl-3,6-dihydropyrimidin- 1 (2H)-yl)benzoic acid (1 -methoxy- 1 -cyclopropylmethoxycarbonylmethyl) ester (Compound 6-68);

[0069] 2-Chloro-4-fluoro-5-(3-methyl-2,6-dioxo-4-trifluoromethyl-3,6-dihydropyrimidin- 1 (2H)-yl)benzoic acid (1 -methoxy- 1 -cyclopropylmethoxycarbonylmethyl) ester (Compound 6-68);

[0070] 2-Chloro-4-fluoro-5-(3-methyl-2,6-dioxo-4-trifluoromethyl-3,6-dihydropyrimidin- 1 (2H)-yl)benzoic acid (1 -methoxy- 1 -cyclopropylmethoxycarbonylmethyl) ester (Compound 6-68);

[0071] 2-Chloro-4-fluoro-5-(3-methyl-2,6-dioxo-4-trifluoromethyl-3,6-dihydropyrimidin- 1 (2H)-yl)benzoic acid (1 -methoxy- 1 -cyclopropylmethoxycarbonylmethyl) ester (Compound 6-68);

[0072] 2-chloro-4-fluoro-5-(5-methyl-6-oxo-4-trifluoromethylpyridazin-l(6H)-yl)benzoic acid (1-ethoxy-l-(2-chloroethoxy)carbonylmethyl) ester (compound 7-88).

[0073] The groups mentioned as substituents Ak, R and R1to R8in formula I, or as groups on phenyl, benzyl or heterocycle, are collective terms and mean the following:

[0074] Halogen means fluorine, chlorine, bromine or iodine.

[0075] All carbon chains, i.e. all alkyl groups, haloalkyl groups, alkenyl groups and alkynyl groups can be straight-chained or branched. For example, C1to C6alkyl groups can be methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, n-pentyl, isopentyl, sec-pentyl, 2-methylbutyl, tert-pentyl, neopentyl, 1,2-dimethylpropyl, 1-ethylpropyl, n-hexyl, isohexyl, sec-hexyl, 1,1-dimethylbutyl, 1,2-dimethylbutyl, 2-methylpentyl, 3-methylpentyl, tert-hexyl, 1,3-dimethylbutyl, neohexyl, 2,3-dimethylbutyl, 3,3-dimethylbutyl, 1-ethylbutyl, 2-ethylbutyl, 1,1,2-trimethylpropyl, 1,2,2-trimethylpropyl, 1-methyl-l-ethylpropyl or 2-methyl-l-ethylpropyl and the like. Similarly, C2to C8alkenyl groups can be vinyl, propenyl, allyl, 1-methylvinyl, 1-butenyl, 2-butenyl, 3-butenyl, 1-methylpropenyl, 2-methylpropenyl, 1-methylallyl, 2-methylallyl, 2,2-dimethylvinyl and the like. C2to C8alkynyl groups can be ethynyl, propynyl, propargyl, 1-butynyl, 2-butynyl, 3-butynyl, 1-methylpropargyl and the like. The multiple bond of the alkenyl or alkynyl group can be in any position in each unsaturated group. C3to C8cycloalkyl means a carbocyclic saturated ring system having 3 to 8 carbon atoms, which can be cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl and the like.

[0076] Haloalkyl, haloalkoxy or haloalkenyl means alkyl, alkoxy or alkenyl, respectively, which is substituted by one or more halogen atoms, which can be the same or different.

[0077] If a group is substituted by another group, it is to be understood that the group is substituted by one or more, identical or different, substituents selected from those mentioned. In addition, the same or different substituents contained in identical or different substituents can be selected independently of one another. The same applies to ring systems formed by different atoms and units.

[0078] In addition, depending on the nature of the substituents and the manner in which they are attached, the compounds of Formula I and their derivatives can exist as stereoisomers. For example, if there is one or more asymmetric carbon atoms, enantiomeric and diastereomeric forms can occur. The stereoisomers can be obtained from a preparation mixture by conventional separation methods, such as by chromatographic separation (e.g., chiral HPLC resolution), or they can be prepared selectively by using stereoselective reactions, using optically active starting materials, intermediates and / or auxiliaries, catalysts, etc.

[0079] The compounds of Formula I of the present application can be prepared by the following methods, wherein the definitions of the various groups are as previously described unless otherwise indicated:

[0080]

[0081] The compounds of Formula I can be prepared from the corresponding compounds of Formula II and substituted alkyloxo carboxylic acid esters with a leaving group (III, commercially available). The reaction is carried out in a suitable solvent at a temperature between -30 °C and the boiling point of the solvent for a period of 0.5 to 48 hours. The solvent can be selected from dichloromethane, chloroform, carbon tetrachloride, acetonitrile, n-hexane, cyclohexane, benzene, toluene, ethyl acetate, DMF, DMA, diethyl ether, methyl tert-butyl ether, THF, DMSO or dioxane, etc. The addition of a base such as triethylamine, DIEA, pyridine, sodium hydroxide, potassium hydroxide, sodium carbonate, potassium carbonate, cesium carbonate, sodium bicarbonate, potassium phosphate, sodium acetate, potassium acetate, sodium methoxide, sodium ethoxide or potassium tert-butoxide, etc. is beneficial to the reaction. In the substituted alkyloxo carboxylic acid esters with a leaving group (III), L is a leaving group such as chloro, bromo, iodo, methylsulfonate, p-methylbenzenesulfonate, etc.

[0082] The compounds of Formula II can be prepared by deprotection of the compounds of Formula IV.

[0083]

[0084] The compounds of Formula IV can be converted to the compounds of Formula II by reaction with a suitable reducing agent at a temperature between -30 °C and the boiling point of the solvent for a period of 0.5 to 48 hours. The solvent can be selected from alcohols such as methanol, ethanol, isopropanol, etc., ethers such as diethyl ether, tetrahydrofuran, dioxane, etc. The reducing agent can be selected from hydrogen gas, catalytic amount of transition metal or catalytic amount of transition metal compound; wherein the transition metal can be selected from the group VIII of the periodic table of elements, preferably Ni, Pd, Pt, etc. (used directly or supported on a medium such as activated carbon, alumina, silica, etc.); the hydrogen gas can be provided from a hydrogen storage cylinder or can be generated in situ from a reactive metal (such as reduced iron powder, reduced zinc powder, etc.) under acidic conditions (such as hydrochloric acid, sulfuric acid) and participate in the reduction reaction. Suitable reducing agents also include metal hydrides, semi-metal hydrides and derivatives thereof, such as lithium aluminum hydride, diisobutylaluminum hydride, sodium borohydride, borane, etc.

[0085] Compounds of formula IV can also be reacted to give compounds of formula II in the presence of a suitable Lewis acid at temperatures between -30 °C and the boiling point of the solvent for a period of 0.5 to 48 hours. Suitable solvents are dichloromethane, chloroform, carbon tetrachloride, acetonitrile, n-hexane, cyclohexane, benzene, toluene, ethyl acetate, DMF, DMA, diethyl ether, methyl-tert-butyl ether, THF, DMSO or dioxane. Suitable Lewis acids are sulfuric acid, hydrochloric acid, phosphoric acid, anhydrous zinc chloride, anhydrous aluminum chloride, boron trifluoride, boron tribromide, sulfur trioxide, iron bromide, titanium tetrachloride, trimethylchlorosilane or trimethyliodosilane.

[0086] Compounds of formula IV can also be hydrolyzed to give compounds of formula II in the presence of a suitable base at temperatures between -30 °C and the boiling point of the solvent for a period of 0.5 to 48 hours. Suitable solvents are methanol, ethanol, acetonitrile, THF, DMSO or dioxane. Suitable bases are sodium hydroxide, potassium hydroxide, sodium carbonate, potassium carbonate, cesium carbonate, sodium bicarbonate, potassium phosphate, sodium acetate, potassium acetate, sodium methoxide, sodium ethoxide or potassium tert-butoxide.

[0087] Compounds of formula IV, wherein Het is selected from Het1, W1and W2are oxygen, X is fluorine, Y is chlorine and R1and R2together with the atoms to which they are attached form a ring, such as methyl 2-chloro-4-fluoro-5-(1,3-dioxohexahydroimidazo[1,5-a]pyridin-2-yl)benzoate (CAS No. 91623-93-7), can be prepared by synthesis as described in EP 104532 A1.

[0088] Compounds of formula IV, wherein Het is selected from Het2, W1is oxygen, X and Y are chlorine, R1is difluoromethyl and R2is methyl, such as methyl 2,4-dichloro-5-(4-difluoromethyl-2,4-dihydro-5-methyl-3H-3-oxo-1,2,4-triazol-2-yl)benzoate (CAS No. 90208-80-3), can be prepared by synthesis as described in JP 58225070 A. Further, compounds of formula IV, wherein Het is selected from Het2, W1is oxygen, X is fluorine, Y is chlorine and R1and R2together with the atoms to which they are attached form a ring, such as isopropyl 2-chloro-4-fluoro-5-(5,6,7,8-tetrahydro-3-oxo-1,2,4-triazolo[4,3-a]pyridin-2(3H)-yl)-benzoate (CAS No. 104799-38-4), can be prepared by synthesis as described in WO 9422860 A1.

[0089] A compound of formula IV, wherein Het is selected from Het3, W1 is oxygen, X is fluorine, Y is chlorine, and R1 and R2 together with the atoms to which they are attached form a ring, such as 2-chloro-4-fluoro-5-(1,3-dioxotetrahydro-1 H- [1,2,4]triazolo[1,2-a]pyridazin-2(3H)-yl)benzoic acid ethyl ester (CAS No. 91150-86-6), can be prepared by synthesis as described in EP 104484 A1 and WO 9527698 A1.

[0090] A compound of formula IV, wherein Het is selected from Het6, W1 and W2 are both oxygen, W3 is sulfur, X is fluorine, Y is chlorine, and R1 and R2 are both methyl, such as 2-chloro-4-fluoro-5-(3,5-dimethyl-4-thioxo-1,3,5-triazin-2,6(1 H,3H)- dion-1 -yl)benzoic acid isopropyl ester (CAS No. 289883-20-1 ), can be prepared by synthesis as described in WO 2000050409 A1.

[0091] A compound of formula IV, wherein Het is selected from Het8, W1 and W2 are both oxygen, X is fluorine, Y is chlorine, R1 is methyl, R2 is trifluoromethyl, and R4 is hydrogen, such as 2-chloro-4-fluoro-5-(3,6-dihydro-3-methyl-2,6-dioxo-4- trifluoromethyl-1 (2H)-pyrimidinyl)benzoic acid isopropyl ester (CAS No. 105756-82-9), can be prepared by synthesis as described in EP 195346 A2, WO 8810254 A1 and WO 2004009561 A1.

[0092] A compound of formula IV, wherein Het is selected from Het 10 , W1 is oxygen, X is fluorine, Y is chlorine, R3 is trifluoromethyl, R4 is methyl, and R8 is hydrogen, such as 2-chloro-4-fluoro-5-(5-methyl-6-oxo-4- trifluoromethyl-1 (6H)-pyridazinyl)benzoic acid ethyl ester (CAS No. 188489-20-5), can be prepared by synthesis as described in WO 9707104 A1.

[0093] A compound of formula IV, wherein Het is selected from Het 11 , X is fluorine, Y is chlorine, R1 and R3 are hydrogen, R3 is trifluoromethyl, and R8 is chlorine, such as 2-chloro-4-fluoro-5-(3-chloro-5- trifluoromethylpyridin-2-yl)benzoic acid isopropyl ester (CAS No. 372136-87-3), can be prepared by synthesis as described in DE 4323916 A1 and WO 2001083459 A2.

[0094] A compound of formula IV, wherein Het is selected from Het 12, W1 and W2 are oxygen, X is fluorine, Y is chlorine, and R1 and R2 together with the atoms to which they are attached form a ring, such as 2-chloro-4-fluoro-5-(1,3,4,5,6,7-hexahydro-1,3-dioxo-2H- isoindol-2-yl)benzoic acid ethyl ester (CAS No. 81663-35-6), which can be prepared by synthesis as described in GB 2071 100 A and EP 97056 A2.

[0095] when Het is selected from Het 13 , W1 is oxygen, R1 is isopropyl, R5 is methyl, X is fluorine, and Y is chlorine, such as 2-chloro-4-fluoro-5-(1,5-dihydro-3-methyl-1 -isopropyl-5-oxo-1,2,4- triazol-4-yl)benzoic acid methyl ester (CAS No. 136143-93-6), which can be prepared by synthesis as described in JP 03106865 A.

[0096] when Het is selected from Het 14 , W1 is oxygen, X is fluorine, Y is chlorine, and R8 is tert-butyl, such as 2-chloro-4-fluoro-5-(5-tert-butyl-2-oxo-1,3,4-oxadiazol-3(2H)-yl)benzoic acid ethyl ester (CAS No. 95089-50-2), which can be prepared by synthesis as described in JP 59148769 A.

[0097] when Het is selected from Het 15 , X is fluorine, Y is chlorine, R1 is difluoromethoxy, R2 is methyl, and R8 is chlorine, such as 2-chloro-4-fluoro-5-(4-chloro-5-difluoromethoxy-1 -methyl-1 H- pyrazol-3-yl)benzoic acid methyl ester (CAS No. 129631 -27-2), which can be prepared by synthesis as described in EP 361 1 14 A1, EP 443059 A1 and EP 647399 A1 ; and, additionally, when Het is selected from Het15, X is fluorine, Y is chlorine, R8 is chlorine, and R1 and R2 together with the atoms to which they are attached form a ring, such as 2-chloro-4-fluoro-5-(3-chloro-4,5,6,7-tetrahydropyrazolo[1,5- a]pyridin-2-yl)benzoic acid methyl ester (CAS No. 153098-75-0), which can be prepared by synthesis as described in JP 2022078425 A.

[0098] The compounds of formula I and their salts, both as mixtures of isomers and as pure isomers, can be used as herbicides. Herbicidal compositions containing the compounds of formula I can be used to control plants in non-crop areas, particularly at high application rates. The compounds of formula I of the present application have good herbicidal activity against many important monocotyledonous and dicotyledonous weeds. While the compounds of the present application have excellent herbicidal activity against monocotyledonous and dicotyledonous weeds, they have little or no damage to important economic crops such as wheat, barley, rye, rice, corn, soybeans and cotton, and do not significantly affect the crops. This effect can be observed particularly at low application rates. The use of the compounds of the present application for the control of weeds in economic crops is therefore also included in the present application.

[0099] The present application also includes herbicidal compositions containing the compounds of formula I as active ingredients. The herbicidal compositions contain from 1 to 99% by weight of the active ingredient. The herbicidal compositions also contain an agriculturally acceptable carrier.

[0100] The herbicidal compositions of the present application can be applied in a variety of formulations. The compounds of the present application are usually dissolved or dispersed in a carrier to formulate the formulations for ease of application as herbicides. For example, the formulations can be prepared as wettable powders or emulsifiable concentrates. Therefore, at least one liquid or solid carrier is added to the compositions, and usually an appropriate surfactant is also added.

[0101] Another embodiment of the present application is a method for controlling weeds, which comprises applying to the weeds or to the locus or surface of the growth medium of the weeds a herbicidally effective amount of the herbicidal compositions of the present application. The more suitable effective amount is usually selected from 1 to 500 g per hectare, and preferably from 2 to 250 g per hectare. For some applications, one or more other herbicides can be added to the herbicidal compositions of the present application, thereby producing additional advantages and effects.

[0102] The compounds of the present application can be used alone or in combination with other known insecticides, fungicides, plant growth regulators or fertilizers.

[0103] It should be understood that various changes and modifications can be made within the scope of the present application as defined in the claims. Method of carrying out the invention

[0104] The following synthesis examples and biological test results are intended to further illustrate the present application but not limit the scope of the subject matter of the present application to the following compounds and / or biological test results. It should not be construed as limiting the scope of the subject matter of the present application to only the following compounds and / or biological test results for those skilled in the art.

[0105] Synthesis Example

[0106] Example 1: Preparation of 2-chloro-4-fluoro-5-(l,3-dioxohexahydroimidazo[l,5- a]pyridin-2(3H)-yl)benzoic acid (l-methoxy-l-ethoxycarbonylmethyl) ester (Compound 1-2)

[0107]

[0108] Synthesis of intermediate 2-chloro-4-fluoro-5-nitrobenzoic acid methyl ester in Step a)

[0109]

[0110] 2-chloro-4-fluoro-5-nitrobenzoic acid (10.98 g, 50.0 mmol) was dissolved in 100 mL of toluene to form a suspension. After the addition of dichlorosulfoxide (7.3 mL, 11.91 g, 100.0 mmol), the mixture was heated to reflux for 5 h to form a clear solution. The toluene and excess dichlorosulfoxide were removed by rotary evaporation. The residual acid chloride was diluted with an appropriate amount of dichloromethane and reserved for use.

[0111] Separately, methanol (1.76 g, 55.0 mmol) and triethylamine (8.4 mL, 6.07 g, 60.0 mmol) were dissolved in 30 mL of dichloromethane to form a solution. The above prepared acid chloride solution was added dropwise to the solution at room temperature. After the addition was completed, the reaction was continued at room temperature for 3 h. The reaction was monitored by TLC to the end point (product spot: SiO2, EtOAc:PE = 1:3, Rf = 0.73). Then, 40 mL of water was added to the reaction mixture. f

[0112] The aqueous layer was extracted with dichloromethane (30 mL x 3). The combined organic phase was washed with sat. NaHCO3(30 mL), water (30 mL), and sat. NaCl (30 mL) successively, dried over anhydrous MgSO4, and concentrated to give a yellow oil. About 11.68 g of a light yellow solid was precipitated upon cooling, which was the ester product with a yield of ~100% (the product was not purified and might contain inorganic salts or residual solvents). The product was used directly in the next step without purification.

[0113] Synthesis of intermediate 2-chloro-4-fluoro-5-nitrobenzoic acid methyl ester in Step a)

[0114]

[0115] ​Unpurified methyl 2-chloro-4-fluoro-5-nitrobenzene (4.67 g, 20.0 mmol) from the previous step was dissolved in 30 mL of tetrahydrofuran and 20 mL of ethanol to form a solution. Iron powder (3.91 g, 70.0 mmol) was added, and concentrated hydrochloric acid (13.7 mL, 160.0 mmol) was slowly added dropwise under an ice-water bath. After the addition was complete, the reaction was carried out at room temperature for 4 h. The reaction was monitored by TLC until the endpoint (product point: SiO2, EtOAc:PE = 1:3, R...). f =0.38), the solvent was removed by rotary evaporation, water (40 mL) was added to the residue, and the mixture was extracted with ethyl acetate (30 mL × 3). The combined organic phases were washed with sat.NaCl (40 mL × 2), dried over anhydrous MgSO4, and concentrated to obtain a yellow oil. After cooling, approximately 3.54 g of yellow solid precipitated, which is the reduction product, with a yield of ~87% (the product was not purified and may contain inorganic salts or solvent residues). The product can be used directly in the next reduction reaction without purification.

[0116] Step c) Synthesis of intermediate methyl 2-chloro-4-fluoro-5-isocyanobenzoate

[0117]

[0118] Methyl 2-chloro-4-fluoro-5-aminobenzoate (2.04 g, 10.0 mmol) and 3–5 drops of triethylamine in toluene (30 mL) were added dropwise to a triphosgene (1.48 g, 5.0 mmol) in toluene (20 mL) under ice-water bath conditions. The reaction mixture was reacted at room temperature for 1 h, then heated under reflux for 4 h. After the reaction was complete, the mixture was cooled to room temperature and the solvent was evaporated under reduced pressure to give 2.07 g of the target product, with a yield of ~90% (the product was not purified and may contain inorganic salts or solvent residues). The product can be used directly in the next reduction reaction without purification. Step d) Synthesis of intermediate methyl 2-chloro-4-fluoro-5-(1,3-dioxohexahydroimidazo[1,5-a]pyridin-2(3H)-yl)benzoate

[0119]

[0120] Methyl 2-chloro-4-fluoro-5-isocyanobenzoate (1.15 g, 5.0 mmol) was dissolved in 20 mL of dichloromethane. Ethyl 2-piperidincarnate (1.57 g, 5.0 mmol) and N,N-diisopropylethylamine (2.59 g, 10.0 mmol) were added sequentially under an ice-water bath. The reaction was carried out overnight at room temperature. The reaction progress was monitored by TLC (product spot: SiO2, EtOAc:PE = 1:1, R...). f =0.75).

[0121] After the reaction was completed, the reaction solution was washed with water (20 mL) and sat. NaCl (20 mL x 2), dried over anhydrous MgS04, and concentrated by adding an appropriate amount of silica gel. Column chromatography (Si02, EtOAc:PE = 1 :2) was used to isolate the product, yielding 1.24 g of the target product with a yield of ~73%.

[0122] Synthesis of intermediate 2-chloro-4-fluoro-5-(l,3-dioxohexahydroimidazo[l,5- a]pyridin-2(3H)-yl)benzoic acid

[0123]

[0124] Methyl 2-chloro-4-fluoro-5-(l,3-dioxohexahydroimidazo[l,5-a]pyridin-2(3H)- yl)benzoate (1.36 g, 4.0 mmol) was dissolved in 6 mL of concentrated sulfuric acid, and 6 mL of water was added. The solution was heated to 100 °C for 3 h. TLC (Si02, EtOAc:PE = 1 : 1, Rf = 0.75 for the starting material and Rf = 0.10 for the product) was used to monitor the reaction until there was no starting material left. After the reaction was completed, the reaction solution was poured into ice water and filtered to obtain 1.02 g of the target product, benzoic acid, as a white powdery solid with a yield of ~78%. f f <0.10) was used to monitor the reaction until there was no starting material left. After the reaction was completed, the reaction solution was poured into ice water and filtered to obtain 1.02 g of the target product, benzoic acid, as a white powdery solid with a yield of ~78%.

[0125] Synthesis of compound 1-2

[0126]

[0127] 2-Chloro-4-fluoro-5-(l,3-dioxohexahydroimidazo[l,5-a]pyridin-2(3H)-yl)benzoic acid (327 mg, 1.0 mmol) and potassium carbonate (152 mg, 1.1 mmol) were dissolved in 5 mL of DMF to form a solution. 2-Bromo-2-methoxyacetic acid ethyl ester (236 mg, 1.2 mmol) was added dropwise at room temperature, and the solution was allowed to react overnight at room temperature. TLC (Si02, EtOAc:PE = 1 : 1, Rf = 0.67 for the product) was used to monitor the reaction progress. f

[0128] After the reaction was completed, the reaction solution was washed with water (20 mL) and sat. NaCl (20 mL x 2), dried over anhydrous MgS04, and concentrated by adding an appropriate amount of silica gel. Column chromatography (Si02, EtOAc:PE = 1 :2) was used to isolate the product, yielding 1.24 g of the target product with a yield of ~73%.

[0129] ​​Example 2: Preparation of 2-chloro-4-fluoro-5-(l,3-dioxotetrahydro-lH- [l,2,4]triazolo[l,2-a]pyridazin-2(3H)-yl)benzoic acid (l-ethoxy-l- ethoxycarbonylmethyl) ester (Compound 2-27)

[0130]

[0131] Synthesis of intermediate 2-chloro-4-fluoro-5-nitrobenzoic acid benzyl ester in Step a)

[0132]

[0133] 2-chloro-4-fluoro-5-nitrobenzoic acid (10.98 g, 50.0 mmol) was dissolved in 100 mL of toluene to form a suspension. After the addition of dichlorosulfoxide (7.3 mL, 11.91 g, 100.0 mmol), the mixture was heated to reflux for 5 h to form a clear solution. The toluene and excess dichlorosulfoxide were removed by rotary evaporation. The residual acyl chloride was diluted with an appropriate amount of dichloromethane and used immediately.

[0134] In a separate flask, benzyl alcohol (5.95 g, 55.0 mmol) and triethylamine (8.4 mL, 6.07 g, 60.0 mmol) were dissolved in 60 mL of dichloromethane to form a solution. The acyl chloride solution prepared above was added dropwise to the solution at room temperature. After the addition was completed, the reaction was continued at room temperature for 3 h. The reaction was monitored by TLC (product spot: SiO2, EtOAc:PE = 1:3, Rf = 0.75) until the end point was reached. Then 120 mL of water was added to the reaction mixture. f

[0135] The aqueous layer was extracted with dichloromethane (25 mL x 3). The combined organic phases were washed successively with sat. NaHCO3(25 mL), water (25 mL), and sat. NaCl (25 mL), dried over anhydrous MgSO4, and concentrated to give a yellow oil. About 17.00 g of a light yellow solid was obtained upon cooling, which was the ester product with a yield of ~110% (the product was not purified and might contain inorganic salts or residual solvents).

[0136] The product was used directly in the next step without purification.

[0137] Synthesis of intermediate 2-chloro-4-fluoro-5-nitrobenzoic acid benzyl ester in Step a)

[0138]

[0139] ​The unpurified 2-chloro-4-fluoro-5-nitrobenzyl benzoate (6.20 g, 20.0 mmol) was dissolved in 30 mL of tetrahydrofuran and 20 mL of ethanol to form a solution, iron powder (3.91 g, 70.0 mmol) was added, and concentrated hydrochloric acid (13.7 mL, 160.0 mmol) was added dropwise slowly under an ice water bath. After the addition was completed, the reaction was allowed to proceed at room temperature for 4 h. The reaction was monitored by TLC until the end point (product spot: SiO2, EtOAc:PE = 1 :3, Rf = 0.40). After the reaction was completed, the solvent was removed by rotary evaporation, water (40 mL) was added to the residue, and the mixture was extracted with ethyl acetate (50 mL x 3). The combined organic phase was washed with sat. NaCl (40 mL x 2), dried over anhydrous MgSO4, and concentrated to give a yellow oil. About 5.00 g of yellow solid was precipitated upon cooling, which was the reduced product with a yield of ~90% (the product was not purified, and it might contain inorganic salts or solvent residues). The product was used directly in the next step without further purification. f f The unpurified 2-chloro-4-fluoro-5-nitrobenzyl benzoate (6.20 g, 20.0 mmol) was dissolved in 30 mL of tetrahydrofuran and 20 mL of ethanol to form a solution, iron powder (3.91 g, 70.0 mmol) was added, and concentrated hydrochloric acid (13.7 mL, 160.0 mmol) was added dropwise slowly under an ice water bath. After the addition was completed, the reaction was allowed to proceed at room temperature for 4 h. The reaction was monitored by TLC until the end point (product spot: SiO2, EtOAc:PE = 1 :3, Rf = 0.40). After the reaction was completed, the solvent was removed by rotary evaporation, water (40 mL) was added to the residue, and the mixture was extracted with ethyl acetate (50 mL x 3). The combined organic phase was washed with sat. NaCl (40 mL x 2), dried over anhydrous MgSO4, and concentrated to give a yellow oil. About 5.00 g of yellow solid was precipitated upon cooling, which was the reduced product with a yield of ~90% (the product was not purified, and it might contain inorganic salts or solvent residues). The product was used directly in the next step without further purification.

[0140] Synthesis of intermediate 2-chloro-4-fluoro-5-nitrobenzyl benzoate

[0141]

[0142] The 2-chloro-4-fluoro-5-nitrobenzyl benzoate (2.80 g, 10.0 mmol) was added dropwise to a solution of triphosgene (1.48 g, 5.0 mmol) in toluene (20 mL) under an ice water bath, and the reaction mixture was allowed to react at room temperature for 1 h, and then heated to reflux for 4 h. After the reaction was completed, the mixture was cooled to room temperature and the solvent was evaporated under reduced pressure to give 2.90 g of the target product with a yield of ~95% (the product was not purified, and it might contain inorganic salts or solvent residues). The product was used directly in the next step without further purification.

[0143] Synthesis of intermediate 2-chloro-4-fluoro-5-nitrobenzyl benzoate

[0144]

[0145] A solution of 2-chloro-4-fluoro-5-nitrobenzyl benzoate (2.80 g, 10.0 mmol) in toluene (30 mL) was added dropwise to a solution of triphosgene (1.48 g, 5.0 mmol) in toluene (20 mL) under an ice water bath, and the reaction mixture was allowed to react at room temperature for 1 h, and then heated to reflux for 4 h. After the reaction was completed, the mixture was cooled to room temperature and the solvent was evaporated under reduced pressure to give 2.90 g of the target product with a yield of ~95% (the product was not purified, and it might contain inorganic salts or solvent residues). The product was used directly in the next step without further purification.

[0146] ​After the reaction was completed, the solvent was removed by rotary evaporation, 20 mL of ethyl acetate and 20 mL of saturated brine were added to the residue to form two layers, the aqueous layer was extracted with ethyl acetate (20 mL x 3), the combined organic phase was washed with water (20 mL) and sat. NaCl (20 mL x 2) successively, dried over anhydrous MgS04, filtered, and concentrated by adding an appropriate amount of silica gel. Column chromatography (Si02, EtOAc:PE = 1:2) was used to separate the product, and about 1.57 g of the target product was obtained with a yield of about 80%.

[0147] Synthesis of intermediate 2-chloro-4-fluoro-5-(1,3-dioxotetrahydro-1H- [1,2,4]triazolo[1,2-a]pyridazine-2(3H)-yl)benzoic acid benzyl ester

[0148]

[0149] Benzyl 2-chloro-4-fluoro-5-(hexahydropyridazine-1-carboxamide)benzoate (1.56 g, 4.0 mmol), pyridine (0.7 ml, 0.64 g, 8.0 mmol) were dissolved in 20 mL of 1,2-dichloroethane successively, and a solution of 3,3,3-trifluoropropionyl chloride (0.60 g, 2.0 mmol) in 10 mL of 1,2-dichloroethane was added dropwise slowly under ice water bath. The reaction was allowed to proceed at room temperature overnight, and the reaction progress was monitored by TLC (Si02, EtOAc:PE = 1:1, R f = 0.70).

[0150] After the reaction was completed, the reaction solution was washed with water (20 mL) and sat. NaCl (20 mL x 2) successively, dried over anhydrous MgS04, and concentrated by adding an appropriate amount of silica gel. Column chromatography (Si02, EtOAc:PE = 1:2) was used to separate the product, and 1.1 g of the target product was obtained with a yield of about 66%.

[0151] Synthesis of intermediate 2-chloro-4-fluoro-5-(1,3-dioxotetrahydro-1H- [1,2,4]triazolo[1,2-a]pyridazine-2(3H)-yl)benzoic acid

[0152]

[0153] Benzyl 2-chloro-4-fluoro-5-(1,3-dioxotetrahydro-1H-[1,2,4]triazolo[1,2- a]pyridazine-2(3H)-yl)benzoate (1.00 g, 2.4 mmol) was dissolved in 10 mL of acetonitrile, and trimethylsilyl iodide (2.40 g, 12.0 mmol) was added thereto at room temperature. The reaction was allowed to proceed at room temperature for 3 h, and the reaction progress was monitored by TLC (Si02, EtOAc:PE = 1:1, R f = 0.70; product point R f <0.10).

[0154] After the reaction was completed, the pH of the system was adjusted to 9 with sat. NaHCO3, and the product was dissolved in water in the form of a sodium salt. The product was then extracted with methyl tert-butyl ether (10 mL x 3) and washed. The water layer was then acidified with hydrochloric acid to pH = 2-3. If solid was precipitated, it was directly filtered to obtain the product. Otherwise, the product was extracted with dichloromethane. The extract was dried and concentrated to obtain 557 mg of white solid, which was the product, in a yield of ~71%.

[0155] Step g) synthesis of compound 2-27

[0156]

[0157] 2-chloro-4-fluoro-5-(l,3-dioxotetrahydro-lH-[l,2,4]triazolo[l,2-a]pyridazin-2(3H)- yl)benzoic acid (328 mg, 1.0 mmol) and potassium carbonate (152 mg, 1.1 mmol) were dissolved in 5 mL of DMF to form a solution. 2-bromo-2-ethoxyacetic acid methyl ester (253 mg, 1.2 mmol) was added dropwise at room temperature, and the reaction was allowed to proceed overnight at room temperature. The progress of the reaction was monitored by TLC (product spot: SiO2, EtOAc:PE = 1:1, Rf = 0.60). f

[0158] After the reaction was completed, 20 mL of ethyl acetate and 20 mL of saturated brine were added to separate the layers. The water layer was extracted with ethyl acetate (10 mL x 3), and the combined organic phase was washed with water (20 mL) and sat. NaCl (20 mL x 2), respectively. After drying over anhydrous MgSO4, the filtrate was concentrated by adding silica gel. Column chromatography (SiO2, EtOAc:PE = 1:3) was used to separate the product, which was 293 mg of compound 2-27 in the form of a light yellow oil, in a yield of 64%.

[0159] Example 3: preparation of 2-chloro-5-(l,3-dioxooctahydro-2H-isoindol-2-yl)benzoic acid (l-methoxy-l-isopentyloxycarbonylmethyl) ester (compound 3-7)

[0160]

[0161] Step a) synthesis of intermediate benzyl 2-chloro-5-nitrobenzoate

[0162]

[0163] ​2-chloro-5-nitrobenzoic acid (10.08 g, 50.0 mmol) was dissolved in 100 mL of toluene to form a suspension. After the addition of dichlorosulfoxide (7.3 mL, 11.91 g, 100.0 mmol), the mixture was heated to reflux for 5 h to form a clear solution. The toluene and excess dichlorosulfoxide were removed by rotary evaporation. The residual acid chloride was diluted with an appropriate amount of dichloromethane and stored for later use.

[0164] Phenylmethanol (5.95 g, 55.0 mmol) and triethylamine (8.4 mL, 6.07 g, 60.0 mmol) were dissolved in 60 mL of dichloromethane to form a solution. The above prepared acid chloride solution was added dropwise at room temperature. After the addition was completed, the reaction was continued at room temperature for 3 h. The reaction was monitored by TLC until completion (product spot: SiO2, EtOAc:PE = 1 :3, Rf = 0.75). Then 120 mL of water was added to the reaction mixture. f

[0165] The aqueous layer was extracted with dichloromethane (25 mL x 3). The combined organic phases were washed successively with sat. NaHCO3(25 mL), water (25 mL), and sat. NaCl (25 mL), dried over anhydrous MgSO4, and concentrated to give a yellow oil. About 14.58 g of a yellow solid was obtained after cooling, which was the ester product with a yield of ~100% (the product was not purified and might contain inorganic salts or residual solvents). The product was used directly in the next step without purification.

[0166] Synthesis of intermediate 2-chloro-5-nitrobenzoic acid

[0167]

[0168] The unpurified 2-chloro-5-nitrobenzyl ester (5.83 g, 20.0 mmol) from the previous step was dissolved in 30 mL of tetrahydrofuran and 20 mL of ethanol to form a solution. Iron powder (3.91 g, 70.0 mmol) was added, and concentrated hydrochloric acid (13.7 mL, 160.0 mmol) was added dropwise slowly under an ice water bath. After the addition was completed, the reaction was continued at room temperature for 4 h. The reaction was monitored by TLC until completion (product spot: SiO2, EtOAc:PE = 1 :3, Rf = 0.40). Then the solvent was removed by rotary evaporation. Water (40 mL) was added to the residue, which was extracted with ethyl acetate (50 mL x 3). The combined organic phases were washed with sat. NaCl (40 mL x 2), dried over anhydrous MgSO4, and concentrated to give a yellow oil. About 4.66 g of a yellow solid was obtained after cooling, which was the reduction product with a yield of ~89% (the product was not purified and might contain inorganic salts or residual solvents). The product was used directly in the next step without purification. f

[0169] ​​Synthesis of intermediate benzyl 2-chloro-5-(l,3-dioxo-octahydro-2H- isoindol-2-yl)benzoate in step c)

[0170]

[0171] Benzyl 2-chloro-5-amino benzoate (2.62 g, 10.0 mmol) was dissolved in 20 mL acetic acid and heated to reflux after the addition of 4,5,6,7-tetrahydroisobenzo-furan-l,3-dione (1.83 g, 12.0 mmol) for 3 h. The reaction was monitored by TLC (SiO2, EtOAc:PE = 1:3, Rf = 0.50) until the starting material, amino benzyl ester (product spot: SiO2, EtOAc:PE = 1:3, Rf = 0.50) was consumed. The acetic acid was removed by distillation under reduced pressure and water (30 mL) was added to the residue. The combined organic phases were washed with sat. NaCl (30 mL x 2), dried over anhydrous MgSO4, filtered and concentrated by the addition of silica gel. Column chromatography (SiO2, EtOAc:PE = 1:6) gave 3.64 g of the desired product in ~92% yield. f

[0172] Synthesis of intermediate 2-chloro-5-(l,3-dioxo-octahydro-2H- isoindol-2-yl)benzoic acid in step d)

[0173]

[0174] Benzyl 2-chloro-5-(l,3-dioxo-octahydro-2H-isoindol-2-yl)benzoate (1.19 g, 3.0 mmol) was dissolved in 10 mL acetonitrile and trimethylsilyl iodide (3.00 g, 15.0 mmol) was added at room temperature. The reaction was allowed to proceed for 3 h at room temperature. The reaction was monitored by TLC (SiO2, EtOAc:PE = 1:3, starting material spot: Rf = 0.50; product spot Rf = 0.10). f f <0.10) until the starting material spot was consumed.

[0175] After the reaction was complete, the pH of the system was adjusted to 9 with sat. NaHCO3, and the product was dissolved as the sodium salt in water. The product was then extracted with methyl tert-butyl ether (10 mL x 3). The aqueous layer was acidified with hydrochloric acid to pH = 2-3. If a solid precipitated, it was filtered to give the product. Otherwise, the product was extracted with dichloromethane. The extract was dried and concentrated to give 670 mg of the product as a white solid in ~73% yield.

[0176] Synthesis of compound 3-7 in step e)

[0177]

[0178] ​​2-Chloro-5-(1,3-dioxooctahydro-2H-isoindol-2-yl)benzoic acid (306 mg, 1.0 mmol) and potassium carbonate (166 mg, 1.2 mmol) were dissolved in 5 mL of DMF to form a solution. 2-bromo-2-methoxyacetic acid isoamyl ester (287 mg, 1.2 mmol) was added dropwise at room temperature, and the reaction was allowed to proceed overnight at room temperature. The reaction progress was monitored by TLC (product spot: SiO2, EtOAc:PE = 1:3, R...). f =0.45).

[0179] After the reaction was complete, 20 mL of ethyl acetate and 20 mL of saturated brine were added to separate the layers. The aqueous layer was extracted with ethyl acetate (10 mL × 3). The combined organic phases were washed successively with water (20 mL) and sat. NaCl (20 mL × 2), dried over anhydrous MgSO4, filtered, and concentrated with an appropriate amount of silica gel. Column chromatography (SiO2, EtOAc:PE = 1:9 → 1:4) yielded 297 mg of compound 3-7, a pale yellow oil, with a yield of 64%.

[0180] Example 4: Preparation of 2-chloro-4-fluoro-5-(1,3-dioxooctahydro-2H-isoindol-2-yl)benzoic acid (1-(2,4-dichlorophenoxy)-1-n-butoxycarbonylmethyl) ester (compound 3-205)

[0181]

[0182] Step a) Synthesis of intermediate 2-chloro-4-fluoro-5-(1,3-dioxooctahydro-2H-isoindol-2-yl)benzoate

[0183]

[0184] Benzyl 2-chloro-4-fluoro-5-aminobenzoate (2.80 g, 10.0 mmol, prepared according to steps a) and b) of Example 2) was dissolved in 20 mL of acetic acid to form a solution. 4,5,6,7-Tetrahydroisobenzofuran-1,3-dione (1.83 g, 12.0 mmol) was added, and the mixture was heated to reflux for 3 h. The reaction was monitored by TLC until no more benzyl 2-aminobenzoate was detected (product spot: SiO2, EtOAc:PE = 1:3, R...). f After removing acetic acid by vacuum distillation (=0.50), water (30 mL) was added to the residue, and the mixture was extracted with ethyl acetate (40 mL × 3). The combined organic phases were washed with sat.NaCl (30 mL × 2), dried over anhydrous MgSO4, filtered, and concentrated with silica gel. Column chromatography (SiO2, EtOAc:PE = 1:6) yielded 3.60 g of the target product, with a yield of ~87%.

[0185] Synthesis of intermediate 2-chloro-4-fluoro-5-(l,3-dioxooctahydro-2H- isoindol-2-yl)benzoic acid in step b)

[0186]

[0187] Benzyl 2-chloro-5-(l,3-dioxooctahydro-2H-isoindol-2-yl)benzoate (1.25 g, 3.0 mmol) was dissolved in 10 mL of acetonitrile, and trimethylsilyl iodide (3.00 g, 15.0 mmol) was added at room temperature. The reaction was allowed to proceed at room temperature for 3 h. TLC (SiO2, EtOAc:PE = 1:3, Rf of starting material = 0.50; Rf of product = 0.30) was used to monitor the reaction to completion. f f <0.1) was used to monitor the reaction to completion.

[0188] After the reaction was completed, the pH of the system was adjusted to 9 with sat. NaHCO3, and the product was dissolved in water as a sodium salt. The product was then extracted with methyl tert-butyl ether (10 mL x 3) and washed. The aqueous layer was acidified with hydrochloric acid to pH = 2-3. If a solid precipitated, it was directly filtered to obtain the product. Otherwise, the product was extracted with dichloromethane, and the extract was dried and concentrated to obtain 728 mg of the product as a white solid in a yield of -75%.

[0189] Synthesis of compound 3-205 in step c)

[0190]

[0191] 2-Chloro-5-(l,3-dioxooctahydro-2H-isoindol-2-yl)benzoic acid (324 mg, 1.0 mmol) and potassium carbonate (166 mg, 1.2 mmol) were dissolved in 5 mL of DMF, and n-butyl 2-bromo-2-(2,4-dichlorophenoxy)acetate (427 mg, 1.2 mmol) was added dropwise at room temperature. The reaction was allowed to proceed at room temperature overnight, and TLC was used to monitor the reaction progress (Rf of product = 0.70). f

[0192] After the reaction was completed, the reaction mixture was partitioned between 20 mL of ethyl acetate and 20 mL of saturated brine. The aqueous layer was extracted with ethyl acetate (10 mL x 3), and the combined organic phase was washed with water (20 mL) and sat. NaCl (20 mL x 2), dried over anhydrous MgSO4, filtered, and concentrated with the addition of an appropriate amount of silica gel. Column chromatography (SiO2, EtOAc:PE = 1:9→1:4) was used to separate the product to obtain 281 mg of compound 3-205 as a light yellow oil in a yield of 47%.

[0193] ​​Example 5: Preparation of 2-chloro-4-fluoro-5-(5-tert-butyl-2-oxo-1,3,4-oxadiazol-3(2H)-yl)benzoic acid (1-ethoxy-1-n-propoxycarbonylmethyl) ester (compound 4-28)

[0194]

[0195] Step a) Synthesis of intermediate 2-fluoro-4-chloro-5-methylaniline

[0196]

[0197] 2-Chloro-4-fluoro-5-nitrotoluene (9.48 g, 50.0 mmol) was dissolved in 50 mL of tetrahydrofuran and 40 mL of ethanol to form a solution. Iron powder (9.78 g, 175.0 mmol) was added, and concentrated hydrochloric acid (34.3 mL, 400.0 mmol) was slowly added dropwise under an ice-water bath. After the addition was complete, the reaction was carried out at room temperature for 6 h. The reaction was monitored by TLC until the endpoint (product point: SiO2, EtOAc:PE = 1:3, R...). f =0.45), the solvent was removed by rotary evaporation, water (70 mL) was added to the residue, and the mixture was extracted with ethyl acetate (60 mL × 3). The combined organic phases were washed with sat.NaCl (60 mL × 2), dried over anhydrous MgSO4, and concentrated to obtain a brown oil. After cooling, approximately 7.40 g of brown solid precipitated, which is the reduction product, with a yield of ~93% (the product was not purified and may contain inorganic salts or solvent residues). The product can be used directly in the next step without further purification.

[0198] Step b) Synthesis of intermediate 2-fluoro-4-chloro-5-methylphenylhydrazine

[0199]

[0200] 2-Fluoro-4-chloro-5-methylaniline (4.47 g, 28.0 mmol) was dissolved in concentrated hydrochloric acid (24.0 mL, 280.0 mmol) and 10 mL of water. An aqueous solution of NaNO2 (2.12 g, 30.8 mmol) (10 mL) was slowly added dropwise under an ice-salt bath. After the addition was complete, the reaction was continued under an ice-salt bath for 0.5 h. Then, a dilute hydrochloric acid solution (20 mL) containing stannous chloride dihydrate (15.71 g, 70.0 mmol) was slowly added dropwise to the above reaction solution. The reaction was continued at low temperature for 2 h. TLC was used to monitor the reaction until the endpoint (product point: SiO2, EtOAc:PE = 1:3, R...). f =0.2), filtered, to obtain about 2.66 g of grayish-white 2-fluoro-4-chloro-5-methylphenylhydrazine hydrochloride solid, yield ~45%.

[0201] Dissolve 2-fluoro-4-chloro-5-methylphenylhydrazine hydrochloride solid in 25% aqueous sodium hydroxide solution (30 mL), extract with dichloromethane (20 mL x 3), dry over anhydrous MgSO4and use directly in the next step.

[0202] Synthesis of intermediate N-(2-fluoro-4-chloro-5-methylphenyl) pivaloylhydrazine in step c)

[0203]

[0204] Add triethylamine (3.5 mL, 2.54 g, 25.1 mmol) to the above solution of 2-fluoro-4-chloro-5-methylphenylhydrazine in dichloromethane (60 mL), slowly drop in a solution of pivaloyl chloride (1.52 g, 12.6 mmol) in dichloromethane (40 mL) under ice-water bath, keep low temperature and continue to react for 2 h, monitor the reaction to the end point by TLC (product spot: SiO2, EtOAc:PE = 1 :3, Rf= 0.4), add 50 mL water to the solution. f

[0205] Extract the aqueous layer with dichloromethane (20 mL x 3), wash the combined organic phase with sat. NaHCO3(40 mL), water (40 mL) and sat. NaCl (40 mL) successively, dry over anhydrous MgSO4, add appropriate amount of silica gel and concentrate. Column chromatography separation (SiO2, EtOAc:PE = 1 :6) to give 2.31 g of the target product with a yield of ~71%.

[0206] Synthesis of intermediate 2-chloro-4-fluoro-5-(5-tert-butyl-2-oxo-l,3,4-oxadiazol-3(2H)-yl)toluene in step d)

[0207]

[0208] Dissolve N-(2-fluoro-4-chloro-5-methylphenyl) pivaloylhydrazine (2.59 g, 10.0 mmol), triethylamine (2.8 mL, 2.03 g, 20.0 mmol) in 20 mL of toluene successively to form a solution, slowly drop in a solution of triphosgene (1.48 g, 5.0 mmol) in toluene under ice-water bath, after the drop is completed, react at room temperature for 1 h and then heat to reflux for 2 h, monitor the reaction to the end point by TLC (product spot: SiO2, EtOAc:PE = 1 :3, Rf= 0.65), then remove toluene by rotary evaporation. Add water (40 mL) to the residue, extract with ethyl acetate (30 mL x 3), wash the combined organic phase with sat. NaCl (30 mL x 2), dry over anhydrous MgSO4, add appropriate amount of silica gel and concentrate. Column chromatography separation (SiO2, EtOAc:PE = 1 :6) to give 2.55 g of the target product with a yield of ~90%. f ​​

[0209] Synthesis of intermediate 2-chloro-4-fluoro-5-(5-tert-butyl-2-oxo-1,3,4-oxadiazol-3(2H)-yl)benzaldehyde

[0210]

[0211] 2-chloro-4-fluoro-5-(5-tert-butyl-2-oxo-1,3,4-oxadiazol-3(2H)-yl)toluene (1.71 g, 6.0 mmol), NBS (3.20 g, 18.0 mmol) and AIBN (1.97 g, 1.2 mmol) were dissolved in 20 mL of carbon tetrachloride to form a suspension, heated to reflux for 2 h, TLC monitored the reaction to the end point (product point: SiO2, EtOAc:PE = 1:3, Rf = 0.68), after the ice water bath to make more NBS precipitate, filtration, reduced pressure distillation concentrated to get yellow oil liquid, direct use in next step. f = 0.68), after the ice water bath to make more NBS precipitate, filtration, reduced pressure distillation concentrated to get yellow oil liquid, direct use in next step.

[0212] The product obtained in the previous step was dissolved in 30 mL of formic acid and 10 mL of water, heated to reflux for 3 h, TLC monitored the reaction to the end point (product point: SiO2, EtOAc:PE = 1:3, Rf = 0.60), after the removal of formic acid by reduced pressure distillation, the residue precipitated light yellow solid, a small amount of ethyl acetate to form a suspension, filtration, to get 1.46 g of target product, yield ~ 82%. f = 0.68), after the ice water bath to make more NBS precipitate, filtration, reduced pressure distillation concentrated to get yellow oil liquid, direct use in next step.

[0213] Synthesis of intermediate 2-chloro-4-fluoro-5-(5-tert-butyl-2-oxo-1,3,4-oxadiazol-3(2H)-yl)benzoic acid

[0214]

[0215] 2-chloro-4-fluoro-5-(5-tert-butyl-2-oxo-1,3,4-oxadiazol-3(2H)-yl)benzaldehyde (0.90 g, 3.0 mmol) was dissolved in 10 mL of water, heated to 50 °C, slowly dropwise addition of KMnO4(0.90 g, 3.0 mmol) aqueous solution (5 mL), after the dropwise addition of temperature to 70 °C for 2 h, TLC (SiO2, EtOAc:PE = 1:3, raw material point: Rf = 0.60; product point Rf = 0.10) monitored the reaction to no raw material point. f = 0.68), after the ice water bath to make more NBS precipitate, filtration, reduced pressure distillation concentrated to get yellow oil liquid, direct use in next step. f <0.10) monitored the reaction to the end point.

[0216] After the reaction was completed, the pH of the system was adjusted to 9 with sat. NaHCO3, the product was dissolved in water as a sodium salt, hot filtration, the filtrate was acidified with hydrochloric acid to pH = 2-3, precipitated 0.64 g of solid target intermediate, yield ~ 68%.

[0217] Step g) Synthesis of compound 4-28

[0218]

[0219] 2-chloro-4-fluoro-5-(5-tert-butyl-2-oxo-l,3,4-oxadiazol-3(2H)-yl)benzoic acid (315 mg, 1.0 mmol) and potassium carbonate (166 mg, 1.2 mmol) were dissolved in 5 mL of DMF to form a solution, 2-bromo-2-ethoxyacetic acid n-propyl ester (270 mg, 1.2 mmol) was added dropwise at room temperature, and the reaction was allowed to proceed overnight at room temperature. The progress of the reaction was monitored by TLC (product spot: Si02, EtOAc:PE = 1:3, Rf = 0.55). f = 0.55).

[0220] After the reaction was completed, 20 mL of ethyl acetate and 20 mL of saturated brine were added to separate the layers, the aqueous layer was extracted with ethyl acetate (10 mL x 3), the combined organic phases were washed successively with water (20 mL) and sat. NaCl (20 mL x 2), dried over anhydrous MgS04, filtered, and concentrated by adding an appropriate amount of silica gel. Column chromatography (Si02, EtOAc:PE = 1:9→ 1:4) gave 307 mg of compound 4-28 as a light yellow oil in a yield of 67%.

[0221] Example 6: Preparation of 2-chloro-4-fluoro-5-(3,5-dimethyl-2,6-oxo-4-thioxo-l,3,5- triazin-l-yl)benzoic acid (l-methoxy-l-methoxycarbonylmethyl) ester (compound 5-126)

[0222]

[0223] Step a) Synthesis of intermediate benzyl 2-chloro-4-fluoro-5-(3,5-dimethyl-2,6-dioxo-4- thioxo-l,3,5-triazin-l-yl)benzoate

[0224]

[0225] Benzyl 5-amino-2-chloro-4-fluorobenzoate (6.10 g, 21.8 mmol, prepared according to steps a) and b) of Example 2), triethylamine (3.5 mL, 2.54 g, 25.1 mmol), and carbonyldiimidazole (8.50 g, 52.4 mmol) were sequentially dissolved in 40 mL of ethyl acetate to form a solution, which was heated to 50 °C for 1 h. After appropriate cooling, 1,3-dimethylthiourea (2.60 g, 25.0 mmol) was added, and the reaction was allowed to proceed at reflux for 2 h. The progress of the reaction was monitored by TLC (product spot: Si02, EtOAc:PE = 1:3, Rf = 0.55). fAfter the reaction was completed, 60 mL of ethyl acetate was added and the mixture was cooled to room temperature.

[0226] The organic phase was washed successively with water (20 mL) and sat. NaCI (20 mL x 2), dried over anhydrous MgS04and concentrated to give a yellow oil which solidified upon cooling to give the condensation product as a yellow solid.

[0227] Synthesis of intermediate 2-chloro-4-fluoro-5-(3,5-dimethyl-2,6-dioxo-4-thioxo- 1,3,5-triazin-l-yl)benzoic acid

[0228]

[0229] Benzyl 2-chloro-4-fluoro-5-(3,5-dimethyl-2,6-dioxo-4-thioxo-l,3,5-triazin-l- yl)benzoate (5.25 g, 12.0 mmol) was dissolved in 25 mL of acetonitrile and trimethylsilyl iodide (5.00 g, 25.0 mmol) was added at room temperature. The reaction was stirred at room temperature for 4 h. TLC (Si02, EtOAc:PE = 1:3, Rf f = 0.60; product Rf f <0.1) until the starting material spot disappeared.

[0230] After the reaction was completed, the pH of the system was adjusted to 9 with sat. NaHC03to make the product form sodium salt which was dissolved in water, then extracted with methyl tert-butyl ether (25 mL x 3) and washed. The aqueous layer was acidified with hydrochloric acid to pH = 2-3, if solid precipitated, it was directly filtered to give the product; otherwise, it was extracted with dichloromethane, the extract was dried and concentrated to give 2.88 g of yellow solid which was the product, yield ~ 69%.

[0231] Synthesis of compound 5-126

[0232]

[0233] 2-Chloro-4-fluoro-5-(3,5-dimethyl-2,6-dioxo-4-thioxo-l,3,5-triazin-l-yl)benzoic acid (346 mg, 1.0 mmol) and potassium carbonate (152 mg, 1.1 mmol) were dissolved in 5 mL of DMF, and 2-bromo-2-methoxyacetic acid methyl ester (200 mg, 1.1 mmol) was added dropwise at room temperature. The reaction was stirred at room temperature overnight, and the progress of the reaction was monitored by TLC (product spot: Si02, EtOAc:PE = 1:3, Rf f = 0.40).

[0234] After the reaction was completed, 20 mL of ethyl acetate and 20 mL of saturated brine were added to separate the layers, and the aqueous layer was extracted with ethyl acetate (10 mL x 3). The combined organic phase was washed with water (20 mL) and sat. NaCl (20 mL x 2), dried over anhydrous MgS04, filtered, and concentrated by adding an appropriate amount of silica gel. Column chromatography (Si02, EtOAc:PE = 1:9→1:4) was used to separate the product, yielding 305 mg of compound 5-126 as a white foamy solid with a yield of 68%.

[0235] Example 7: Preparation of 2-chloro-4-fluoro-5-(3-methyl-2,6-dioxo-4- trifluoromethyl-3,6-dihydropyrimidin-l(2H)-yl)benzoic acid (l-methoxy-l- methoxycarbonylmethyl) ester (compound 6-51)

[0236]

[0237] Synthesis of intermediate 2-chloro-4-fluoro-5-(2,6-dioxo-4-trifluoromethyl-3,6- dihydropyrimidin-l(2H)-yl)benzyl benzoate in step a)

[0238]

[0239] To 100 mL of DMF, 60% sodium hydride (2.88 g, 72.0 mmol) was added portionwise under an ice-water bath, and after stirring for a while, 3-amino-4,4,4- trifluorocrotonic acid ethyl ester (10.99 g, 60.0 mmol) was added slowly until no more bubbles were generated, followed by dropwise addition of N,N-dimethylaminocarbonyl chloride (7.10 g, 66.0 mmol). The reaction was allowed to proceed overnight at room temperature, and after TLC monitoring of the reaction to the end point (product spot: Si02, EtOAc:PE = 1:3, Rf= 0.50), the mixture was slowly poured into 200 mL of ice-water mixture, extracted with ethyl acetate (80 mL x 3), and the combined organic phase was washed with sat. NaHC03(100 mL), water (100 mL), and sat. NaCl (100 mL) successively, dried over anhydrous MgS04, filtered, and concentrated by adding an appropriate amount of silica gel. Column chromatography (Si02, EtOAc:PE = 1:9→1:3) was used to separate the product, yielding about 7.20 g of the target product, 3-(3,3-dimethylureido)-4,4,4,-trifluorocrotonic acid ethyl ester, with a yield of ~47%, which was used directly in the next step. f = 0.50) after TLC monitoring of the reaction to the end point (product spot: Si02, EtOAc:PE = 1:3, Rf= 0.50), the mixture was slowly poured into 200 mL of ice-water mixture, extracted with ethyl acetate (80 mL x 3), and the combined organic phase was washed with sat. NaHC03(100 mL), water (100 mL), and sat. NaCl (100 mL) successively, dried over anhydrous MgS04, filtered, and concentrated by adding an appropriate amount of silica gel. Column chromatography (Si02, EtOAc:PE = 1:9→1:3) was used to separate the product, yielding about 7.20 g of the target product, 3-(3,3-dimethylureido)-4,4,4,-trifluorocrotonic acid ethyl ester, with a yield of ~47%, which was used directly in the next step.

[0240] Benzyl 2-chloro-4-fluoro-5-amino benzoate (2.80 g, 10.0 mmol, prepared according to steps a) and b) of example 2) was dissolved in 30 mL of acetic acid and 3-(3,3-dimethylureido)-4,4,4,-trifluorocrotonic acid ethyl ester (2.80 g, 11.0 mmol) was added and the reaction mixture was heated to reflux for 5 h. The reaction was monitored by TLC (product spot: SiO2, EtOAc:PE = 1 :3, Rf = 0.30) until completion. The acetic acid was removed by rotary evaporation and water (40 mL) was added to the residue. The aqueous phase was extracted with ethyl acetate (30 mL x 3) and the combined organic phases were washed with sat. NaCI (30 mL x 2), dried over anhydrous MgSO4and concentrated to give 3.98 g of a yellow oil in ~90% yield which was used directly in the next step. f Step b) Synthesis of intermediate benzyl 2-chloro-4-fluoro-5-(3-methyl-2,6-dioxo-4- trifluoromethyl-3,6-dihydropyrimidin-l(2H)-yl)benzoate

[0241] Step c) Synthesis of intermediate 2-chloro-4-fluoro-5-(3-methyl-2,6-dioxo-4- trifluoromethyl-3,6-dihydropyrimidin-l(2H)-yl)benzoic acid

[0242]

[0243] Benzyl 2-chloro-4-fluoro-5-(2,6-dioxo-4-trifluoromethyl-3,6-dihydropyrimidin-l(2H)- yl)benzoate (2.21 g, 5.0 mmol) and potassium carbonate (0.83 g, 6.0 mmol) were dissolved in 10 mL of DMF and the reaction mixture was left to stir at room temperature overnight after the dropwise addition of iodomethane (0.78 g, 5.5 mmol). The reaction progress was monitored by TLC (product spot: SiO2, EtOAc:PE = 1 :3, Rf = 0.43). f

[0244] After completion of the reaction, the mixture was partitioned between 30 mL of ethyl acetate and 30 mL of saturated brine. The aqueous phase was extracted with ethyl acetate (20 mL x 3) and the combined organic phases were washed with water (30 mL) and sat. NaCI (30 mL x 2), dried over anhydrous MgSO4, filtered and concentrated with the addition of silica gel. Column chromatography (SiO2, EtOAc:PE = 1 :9→ 1 :4) gave 1.98 g of the target product in ~87% yield.

[0245] Step c) Synthesis of intermediate 2-chloro-4-fluoro-5-(3-methyl-2,6-dioxo-4- trifluoromethyl-3,6-dihydropyrimidin-l(2H)-yl)benzoic acid

[0246]

[0247] ​Benzyl 2-chloro-4-fluoro-5-(3-methyl-2,6-dioxo-4-trifluoromethyl-3,6- dihydropyrimidin-l(2H)-yl)benzoate (1.37 g, 3.0 mmol) was dissolved in 10 mL of acetonitrile, and trimethylsilyl iodide (3.00 g, 15.0 mmol) was added at room temperature. The reaction was allowed to proceed at room temperature for 3 h. The reaction was monitored by TLC (SiO2, EtOAc:PE = 1 :3, Rf = 0.43; product Rf = 0.10). f f The reaction was monitored to completion by TLC (SiO2, EtOAc:PE = 1 :3, Rf = 0.43; product Rf = 0.10).

[0248] After the reaction was complete, the pH of the system was adjusted to 9 with sat. NaHCO3, and the product was allowed to form a sodium salt in water. The product was then extracted with methyl tert-butyl ether (10 mL x 3) and washed. The aqueous layer was acidified with HCl to pH = 2-3. If a solid precipitated, it was filtered to obtain the product. Otherwise, the product was extracted with dichloromethane. The extract was dried and concentrated to obtain 847 mg of a white solid, which was the product, in a yield of ~77%.

[0249] Step d) Synthesis of compound 6-51

[0250]

[0251] Benzyl 2-chloro-4-fluoro-5-(3-methyl-2,6-dioxo-4-trifluoromethyl-3,6- dihydropyrimidin-l(2H)-yl)benzoate (1.37 g, 3.0 mmol) was dissolved in 10 mL of acetonitrile, and trimethylsilyl iodide (3.00 g, 15.0 mmol) was added at room temperature. The reaction was allowed to proceed at room temperature for 3 h. The reaction was monitored by TLC (SiO2, EtOAc:PE = 1 :3, Rf = 0.43; product Rf = 0.10). f

[0252] After the reaction was complete, the pH of the system was adjusted to 9 with sat. NaHCO3, and the product was allowed to form a sodium salt in water. The product was then extracted with methyl tert-butyl ether (10 mL x 3) and washed. The aqueous layer was acidified with HCl to pH = 2-3. If a solid precipitated, it was filtered to obtain the product. Otherwise, the product was extracted with dichloromethane. The extract was dried and concentrated to obtain 847 mg of a white solid, which was the product, in a yield of ~77%.

[0253] Example 8: Preparation of 2-chloro-4-fluoro-5-(3-methyl-2,6-dioxo-4- trifluoromethyl-3,6-dihydropyrimidin-l(2H)-yl)benzoic acid (l-methoxy-l- cyclopropylmethoxycarbonylmethyl) ester (compound 6-68)

[0254] ​​

[0255] 2-chloro-4-fluoro-5-(3-methyl-2,6-dioxo-4-trifluoromethyl-3,6-dihydropyrimidin- 1 (2H)-yl)benzoic acid (367 mg, 1.0 mmol, prepared according to step c of Example 7) and potassium carbonate (166 mg, 1.2 mmol) were dissolved in 5 mL of DMF to form a solution, 2-cyclopropylmethoxycarbonyl-2-bromoethanol (268 mg, 1.2 mmol) was added dropwise at room temperature, and the reaction was allowed to proceed overnight at room temperature. The progress of the reaction was monitored by TLC (product spot: SiO2, EtOAc:PE = 1 :3, Rf = 0.48). f

[0256] After the reaction was completed, 20 mL of ethyl acetate and 20 mL of saturated brine were added to separate the layers, and the aqueous layer was extracted with ethyl acetate (10 mL x 3). The combined organic phases were washed successively with water (20 mL) and sat. NaCl (20 mL x 2), dried over anhydrous MgSO4, filtered, and concentrated by adding silica gel in an appropriate amount. Column chromatography (SiO2, EtOAc:PE = 1 :9→1 :4) was performed to obtain 351 mg of compound 6-68 as a light yellow oil in a yield of 69%.

[0257] Example 9: Preparation of 2-chloro-4-fluoro-5-(4-trifluoromethyl-6-oxopyridazin-1(6H)- yl)benzoic acid (1-methoxy-1-(2-chloroethoxy)carbonylmethyl) ester (compound 7-13)

[0258]

[0259] Synthesis of intermediate 2-chloro-4-fluoro-5-hydrazinylbenzoic acid methyl ester hydrochloride in step a

[0260]

[0261] Methyl 2-chloro-4-fluoro-5-amino benzoate (4.07 g, 20.0 mmol, prepared according to steps a and b of Example 1) was dissolved in concentrated hydrochloric acid (17.0 mL, 200.0 mmol) and 5 mL of water, and an aqueous solution (5 mL) of NaNO2(1.52 g, 22.0 mmol) was slowly added dropwise under an ice-salt bath. After the dropwise addition was completed, the reaction was continued for 0.5 h under an ice-salt bath, and a solution of stannous chloride dihydrate (11.28 g, 50.0 mmol) in dilute hydrochloric acid (20 mL) was slowly added dropwise to the above reaction solution. The reaction was continued for 2 h under low temperature, and the progress of the reaction was monitored by TLC (product spot: SiO2, EtOAc:PE = 1 :3, Rf = 0.20). Filtration resulted in about 1.99 g of off-white 2-chloro-4-fluoro-5-hydrazinylbenzoic acid methyl ester hydrochloride solid in a yield of ~39%. f ​​

[0262] Synthesis of intermediate 2-chloro-4-fluoro-5-(3,3,3-trifluoro-2-oxopropylidenehydrazino)benzoic acid methyl ester

[0263]

[0264] Sodium acetate (2.46 g, 30.0 mmol), 1,1-dibromo-3,3,3-trifluoroacetone (2.70 g, 10.0 mmol) were dissolved in 20 mL water, heated to 80 °C for 1 h, then cooled to 5 °C in ice water bath, 2-chloro-4-fluoro-5-hydrazinobenzoic acid methyl ester hydrochloride (1.28 g, 5.0 mmol) was added in portions, TLC monitored the reaction to the end point (product spot: SiO2, EtOAc:PE = 1:3, Rf= 0.65), then filtered to get 1.36 g yellow powder solid, which was the target product, yield ~ 83%. f

[0265] Synthesis of intermediate 2-chloro-4-fluoro-5-(4-trifluoromethyl-6-oxopyridazin-1(6H)-yl)benzoic acid methyl ester

[0266]

[0267] 2-chloro-4-fluoro-5-(3,3,3-trifluoro-2-oxopropylidenehydrazino)benzoic acid methyl ester (1.63 g, 5.0 mmol), ethoxyformylmethylene triphenylphosphonium bromide (1.92 g, 5.5 mmol) were dissolved in 30 mL dry tetrahydrofuran, heated to reflux for 2 h, TLC monitored the reaction to the end point (product spot: SiO2, EtOAc:PE = 1:3, Rf= 0.68), then rotary evaporated to remove the solvent, water (30 mL) was added to the residue, extracted with ethyl acetate (20 mL x 3), the combined organic phase was washed with sat. NaCl (30 mL x 2), dried over anhydrous MgSO4, filtered, concentrated with silica gel. Column chromatography separation (SiO2, EtOAc:PE = 1:9→1:6), to get 1.14 g target product, yield ~ 65%. f

[0268] Synthesis of intermediate 2-chloro-4-fluoro-5-(4-trifluoromethyl-6-oxopyridazin-1(6H)-yl)benzoic acid

[0269]

[0270] ​​Methyl 2-chloro-4-fluoro-5-(5-methyl-6-oxo-4-trifluoromethylpyridazine-1(6H)-yl)benzoate (1.05 g, 3.0 mmol) was dissolved in 5 mL of concentrated sulfuric acid, and 5 mL of water was added. The mixture was then heated to 100 °C and reacted for 3 h. TLC (SiO2, EtOAc:PE = 1:3, starting material point: R) was performed. f =0.68; Product point R f <0.10) Monitor the reaction until no starting material is detected. After the reaction is complete, pour the reaction solution into ice water, filter, and dry to obtain 753 mg of white powdery solid, which is the target intermediate, with a yield of ~77%.

[0271] Step e) Synthesis of compounds 7-13

[0272]

[0273] 2-Chloro-4-fluoro-5-(4-trifluoromethyl-6-oxopyridazin-1(6H)-yl)benzoic acid (326 mg, 1.0 mmol) and potassium carbonate (166 mg, 1.2 mmol) were dissolved in 5 mL of DMF to form a solution. 2-bromo-2-methoxyacetic acid-2-chloroethyl ester (278 mg, 1.2 mmol) was added dropwise at room temperature, and the reaction was allowed to proceed overnight at room temperature. The reaction progress was monitored by TLC (product spot: SiO2, EtOAc:PE = 1:3, R...). f =0.55).

[0274] After the reaction was complete, 20 mL of ethyl acetate and 20 mL of saturated brine were added to separate the layers. The aqueous layer was extracted with ethyl acetate (10 mL × 3). The combined organic phases were washed successively with water (20 mL) and sat.NaCl (20 mL × 2), dried over anhydrous MgSO4, filtered, and concentrated with an appropriate amount of silica gel. Column chromatography (SiO2, EtOAc:PE = 1:9 → 1:4) yielded 287 mg of compound 7-13, a pale yellow oil, with a yield of 59%.

[0275] Example 10: Preparation of 2-chloro-4-fluoro-5-(5-methyl-6-oxo-4-trifluoromethylpyridazine-1(6H)-yl)benzoic acid (1-ethoxy-1-(2-chloroethoxy)carbonylmethyl) ester (compounds 7-88)

[0276]

[0277] Step a) Synthesis of intermediate methyl 2-chloro-4-fluoro-5-(5-methyl-6-oxo-4-trifluoromethylpyridazine-1(6H)-yl)benzoate

[0278]

[0279] Methyl 2-chloro-4-fluoro-5-(3,3,3-trifluoro-2-oxopropylidenehydrazino)benzoate (1.63 g, 5.0 mmol, prepared according to the procedure of Example 9, steps a) and b) was dissolved in 30 mL of dry tetrahydrofuran, ethoxyformylethylene phosphine triphenyl (1.99 g, 5.5 mmol) was added and the reaction was heated to reflux for 2 h. The reaction was monitored by TLC (Si02, EtOAc:PE = 1 :3, Rf = 0.70) until the starting material was consumed. The solvent was removed by rotary evaporation and water (30 mL) was added to the residue. The mixture was extracted with EtOAc (20 mL x 3) and the combined organic phases were washed with sat. NaCI (30 mL x 2), dried over anhydrous MgS04, filtered and concentrated by addition of silica gel. The residue was purified by column chromatography (Si02, EtOAc:PE = 1 :9→ 1 :6) to give 1.15 g of the desired product in ~63% yield. f Step b) Synthesis of intermediate 2-chloro-4-fluoro-5-(5-methyl-6-oxo-4- trifluoromethylpyridazin-l(6H)-yl)benzoic acid

[0280] Step b) Synthesis of intermediate 2-chloro-4-fluoro-5-(5-methyl-6-oxo-4- trifluoromethylpyridazin-l(6H)-yl)benzoic acid

[0281]

[0282] Methyl 2-chloro-4-fluoro-5-(5-methyl-6-oxo-4-trifluoromethylpyridazin-l(6H)- yl)benzoate (1.09 g, 3.0 mmol) was dissolved in 5 mL of concentrated sulfuric acid and 5 mL of water was added. The reaction was heated to 100 °C for 3 h. The reaction was monitored by TLC (Si02, EtOAc:PE = 1 :3, Rf = 0.70 for the starting material; Rf = 0.10 for the product) until the starting material was consumed. After the reaction was complete, the reaction mixture was poured into ice water and the solid was filtered and dried to give 741 mg of the desired product as a white powder in ~71% yield. f Step b) Synthesis of intermediate 2-chloro-4-fluoro-5-(5-methyl-6-oxo-4- trifluoromethylpyridazin-l(6H)-yl)benzoic acid f

[0283] Step g) Synthesis of compound 7-88

[0284]

[0285] Methyl 2-chloro-4-fluoro-5-(5-methyl-6-oxo-4-trifluoromethylpyridazin-l(6H)- yl)benzoate (1.09 g, 3.0 mmol) was dissolved in 5 mL of concentrated sulfuric acid and 5 mL of water was added. The reaction was heated to 100 °C for 3 h. The reaction was monitored by TLC (Si02, EtOAc:PE = 1 :3, Rf = 0.70 for the starting material; Rf = 0.10 for the product) until the starting material was consumed. After the reaction was complete, the reaction mixture was poured into ice water and the solid was filtered and dried to give 741 mg of the desired product as a white powder in ~71% yield. f Step b) Synthesis of intermediate 2-chloro-4-fluoro-5-(5-methyl-6-oxo-4- trifluoromethylpyridazin-l(6H)-yl)benzoic acid

[0286] ​After the reaction was completed, 20 mL of ethyl acetate and 20 mL of saturated brine were added to separate the layers, the water layer was extracted with ethyl acetate (10 mL x 3), the combined organic phase was washed with water (20 mL) and sat. NaCl (20 mL x 2) in turn, dried over anhydrous MgSO4, filtered, and concentrated by adding an appropriate amount of silica gel. Column chromatography (SiO2, EtOAc:PE = 1:9→1:4) was used to separate and obtain 268 mg of compound 7-88, a light yellow oil, with a yield of 52%.

[0287] Other compounds represented by Formula I can be obtained by replacing the starting material, the corresponding material required in the preparation process, intermediates, etc. as described above. The structures and physical properties of some of the compounds represented by Formula I are shown in Tables 1-7.

[0288]

[0289] Table 1

[0290]

[0291]

[0292]

[0293]

[0294]

[0295] Table 2

[0296]

[0297]

[0298]

[0299]

[0300] Table 3

[0301]

[0302]

[0303]

[0304]

[0305]

[0306]

[0307]

[0308]

[0309]

[0310]

[0311]

[0312]

[0313]

[0314] Table 4

[0315]

[0316]

[0317]

[0318]

[0319]

[0320] Table 5

[0321]

[0322]

[0323]

[0324]

[0325]

[0326]

[0327]

[0328]

[0329]

[0330]

[0331]

[0332]

[0333]

[0334]

[0335] Table 6

[0336]

[0337]

[0338]

[0339]

[0340]

[0341]

[0342]

[0343] Table 7

[0344]

[0345]

[0346]

[0347]

[0348]

[0349]

[0350]

[0351]

[0352] Table 8

[0353]

[0354]

[0355]

[0356]

[0357] Bioassay Examples

[0358] Example 11: Testing of herbicidal activity

[0359] Stem-leaf activity test: Broadleaf weed (Amaranthus tricolor, Capsella bursa-pastoris, Solanum nigrum), gramineous weed (Digitaria sanguinalis, Echinocloa crus-galli, Leptochloa chinensis) or sedge weed (Commelina communis) seeds were respectively sowed in a 5 cm diameter plastic cup with nutrient soil, covered with 0.1-0.5 cm soil after sowing, flattened, and absorbed water from the bottom of the plastic cup, and then placed in a greenhouse for cultivation according to the conventional method. When the weeds had 2-3 leaves, stem-leaf spraying treatment was performed.

[0360] Soil activity test: The sowing method was the same as that in the stem-leaf activity test, and soil spraying treatment was performed 24 h after sowing.

[0361] Test and efficacy evaluation method: The original drug was dissolved in N,N-dimethylformamide solvent, and then the required concentration of the test solution was prepared with 0.1% Tween 80 water according to the test requirements. According to the test design dose, spraying treatment was performed on a 3WP-2000 walking type spraying tower (manufactured by Nanjing Agricultural Machinery Institute) (spraying pressure 0.3 MPa, spraying amount 45 mL / m 2 , nozzle model TP6501E, spraying height 300 mm, nozzle walking speed 320 mm / s), and the test was designed with 3 replicates. After the test materials were treated with the drug, they were naturally air-dried and then transferred to a greenhouse for cultivation according to the conventional method. The weed reaction symptoms were observed and recorded regularly, and the control effect of the test agent on weeds was investigated 14 days after treatment, which was represented by 0-100%. "0" represents no control effect, and "100%" represents that the weeds are completely killed.

[0362] The common name, English name and Latin name of the weeds used in the test are as follows:

[0363] Amaranthus tricolor (three-colored amaranth);

[0364] Capsella bursa-pastoris (shepherd's purse);

[0365] Solanum nigrum (black nightshade);

[0366] Digitaria sanguinalis (large crabgrass);

[0367] Echinocloa crus-galli (barnyard grass);

[0368] Leptochloa chinensis (Chinese sprangletop);

[0369] Rice flatsedge (Cyperus iria).

[0370] The results of the herbicidal activity test of the stem-leaf treatment showed that the compounds of formula I generally had good control effect on broadleaf weeds. Some of the tested compounds had control effect of 80% or more at the application dose of 75 g a.i. / hm 2 excellent control effect on amaranth, with control effect of 80% or more. For example, compounds 2-1, 2-26, 3-3, 3-7, 3-41, 3-51, 3-101, 3-102, 3-127, 3-129, 3-152, 3-176, 4-3, 4-5, 4-6, 4-13, 4-28, 5-2, 5-7, 5-126, 5-127, 5-128, 5-131, 5-133, 5-134, 5-143, 5-151, 5-152, 5-156, 5-177, 5-201, 6-1, 6-2, 6-27, 6-51, 6-52, 6-53, 6-55, 6-56, 6-58, 6-64, 6-68, 6-76, 6-77, 6-79, 6-81, 6-89, 6-93, 7-1, 7-2, 7-3, 7-5, 7-6, 7-8, 7-13, 7-18, 7-26, 7-27, 7-28, 7-30, 7-31, 7-33, 7-43, 7-51, 7-52, 7-53, 7-55, 7-56, 7-58, 7-63, 7-68, 7-76, 7-77, 7-78, 7-80, 7-88, 7-93, 8-1, 8-2, 8-26 and 8-27.

[0371] The results of the herbicidal activity test of the stem-leaf treatment showed that the compounds of formula I generally had good control effect on broadleaf weeds. Some of the tested compounds had control effect of 80% or more at the application dose of 75 g a.i. / hm 2excellent control effect on the plantago asiatica, and the control effect is not less than 80%. For example, compounds 2-1, 3-127, 4-2, 4-5, 4-13, 4-27, 4-28, 4-30, 5-51, 5-126, 5-128, 5-131, 5-134, 5-143, 5-151, 5-156, 5-177, 6-1, 6-2, 6-27, 6-51, 6-52, 6-53, 6-55, 6-56, 6-58, 6-64, 6-68, 6-76, 6-77, 6-79, 6-81, 6-89, 6-93, 7-1, 7-2, 7-3, 7-5, 7-6, 7-8, 7-13, 7-18, 7-26, 7-27, 7-28, 7-30, 7-31, 7-33, 7-43, 7-52, 7-53, 7-55, 7-56, 7-58, 7-63, 7-68, 7-76, 7-77, 7-78, 7-80, 7-88, 7-93, 8-1, 8-2, 8-26 and 8-27.

[0372] The results of the stem and leaf treatment herbicidal activity test show that the compounds of formula I generally have good control effect on broadleaf weeds. Some of the tested compounds have good control effect on broadleaf weeds at the application dose of 75 g a.i. / hm 2 excellent control effect on the plantago asiatica, and the control effect is not less than 80%. For example, compounds 2-1, 3-101, 3-102, 3-127, 5-126, 5-127, 5-128, 5-131, 5-134, 5-143, 5-151, 5-152, 5-156, 5-177, 5-201, 6-1, 6-2, 6-27, 6-51, 6-52, 6-53, 6-55, 6-56, 6-58, 6-64, 6-68, 6-76, 6-77, 6-79, 6-81, 6-89, 6-93, 7-1, 7-2, 7-3, 7-5, 7-6, 7-8, 7-13, 7-18, 7-26, 7-27, 7-28, 7-30, 7-31, 7-33, 7-43, 7-52, 7-56, 7-58, 7-63, 7-78, 7-80, 7-88, 7-93, 8-1, 8-2, 8-26 and 8-27.

[0373] The results of the stem and leaf treatment herbicidal activity test show that the compounds of formula I generally have good control effect on broadleaf weeds. Some of the tested compounds have good control effect on broadleaf weeds at the application dose of 75 g a.i. / hm 2The following compounds have good control effect on barnyardgrass, and the control effect is not less than 60%. For example, compounds 2-1, 2-2, 2-43, 2-26, 3-102, 3-127, 4-5, 5-26, 5-126, 5-127, 5-128, 5-131, 5-134, 5-143, 5-151, 5-201, 6-1, 6-2, 6-27, 6-51, 6-52, 6-53, 6-55, 6-56, 6-58, 6-64, 6-68, 6-76, 6-77, 6-79, 6-81, 6-89, 6-93, 7-1, 7-2, 7-3, 7-5, 7-6, 7-8, 7-13, 7-18, 7-26, 7-27, 7-28, 7-30, 7-31, 7-33, 7-43, 8-1, 8-2, 8-26 and 8-27.

[0374] The results of the stem-leaf treatment herbicidal activity test show that the compounds of Formula I generally have good control effect on gramineous weeds. Some of the tested compounds have good control effect on gramineous weeds at the application dose of 75 g a.i. / hm 2 The following compounds have good control effect on barnyardgrass, and the control effect is not less than 60%. For example, compounds 5-126, 5-134, 5-151, 6-51, 6-53, 6-55, 7-3, 7-5, 7-6, 7-13, 7-26, 7-27, 7-28, 7-30, 7-31, 7-33, 7-43, 7-52, 7-77, 7-88, 7-93, 8-1, 8-2, 8-26 and 8-27.

[0375] The results of the stem-leaf treatment herbicidal activity test show that the compounds of Formula I generally have good control effect on gramineous weeds. Some of the tested compounds have good control effect on gramineous weeds at the application dose of 75 g a.i. / hm 2The following compounds have excellent control effect on Euphorbia humifusa, and the control effect is not less than 60%. For example, compounds 2-1, 2-2, 2-43, 2-26, 2-27, 3-2, 3-101, 3-127, 3-152, 3-176, 5-1, 5-2, 5-26, 5-29, 5-51, 5-126, 5-127, 5-128, 5-131, 5-133, 5-134, 5-143, 5-151, 5-152, 5-156, 5-177, 5-201, 6-1, 6-2, 6-27, 6-51, 6-52, 6-53, 6-55, 6-56, 6-58, 6-64, 6-68, 6-76, 6-79, 6-81, 6-89, 6-93, 7-1, 7-2, 7-3, 7-5, 7-6, 7-8, 7-13, 7-18, 7-26, 7-27, 7-28, 7-30, 7-31, 7-33, 7-43, 7-52, 7-53, 7-55, 7-68, 7-77, 7-78, 7-80, 7-88, 7-93, 8-1, 8-2, 8-26 and 8-27.

[0376] The results of the stem and leaf treatment herbicidal activity test show that the compounds of Formula I generally have good control effect on Cyperaceae weeds. Some of the tested compounds have good control effect on Cyperus iria L. at the application dose of 75 g a.i. / hm 2 The following compounds have excellent control effect on Euphorbia humifusa, and the control effect is not less than 60%. For example, compounds 2-1, 2-2, 2-43, 2-26, 2-27, 3-2, 3-101, 3-127, 3-152, 3-176, 5-1, 5-2, 5-26, 5-29, 5-51, 5-126, 5-127, 5-128, 5-131, 5-133, 5-134, 5-143, 5-151, 5-152, 5-156, 5-177, 5-201, 6-1, 6-2, 6-27, 6-51, 6-52, 6-53, 6-55, 6-56, 6-58, 6-64, 6-68, 6-76, 6-79, 6-81, 6-89, 6-93, 7-1, 7-2, 7-3, 7-5, 7-6, 7-8, 7-13, 7-18, 7-26, 7-27, 7-28, 7-30, 7-31, 7-33, 7-43, 7-52, 7-53, 7-55, 7-68, 7-77, 7-78, 7-80, 7-88, 7-93, 8-1, 8-2, 8-26 and 8-27.

[0377] The results of the soil treatment herbicidal activity test show that the compounds of Formula I generally have good control effect on broadleaf weeds. Some of the tested compounds have good control effect on broadleaf weeds at the application dose of 75 g a.i. / hm 2The following compounds have excellent control effect on gooseweed, and the control effect is not less than 80%. For example, compounds 2-1, 2-43, 2-26, 3-1, 3-2, 3-129, 3-152, 3-176, 4-3, 4-13, 5-2, 5-26, 5-29, 5-76, 5-128, 5-131, 5-133, 5-134, 5-143, 5-151, 5-156, 5-177, 5-201, 6-1, 6-2, 6-27, 6-51, 6-52, 6-53, 6-55, 6-56, 6-58, 6-64, 6-68, 6-76, 6-77, 6-79, 6-81, 6-89, 6-93, 7-1, 7-2, 7-3, 7-5, 7-6, 7-8, 7-13, 7-18, 7-26, 7-27, 7-28, 7-30, 7-31, 7-33, 7-43, 7-51, 7-52, 7-53, 7-55, 7-56, 7-58, 7-63, 7-68, 7-76, 7-77, 7-78, 7-80, 7-88, 7-93, 8-1, 8-2, 8-26 and 8-27.

[0378] The soil treatment herbicidal activity test results show that the compounds of formula I generally have good control effect on broadleaf weeds. Some of the tested compounds have good control effect on broadleaf weeds at the application dose of 75 g a.i. / hm 2 The following compounds have excellent control effect on gooseweed, and the control effect is not less than 80%. For example, compounds 2-1, 2-43, 2-26, 3-1, 3-2, 3-129, 3-152, 3-176, 4-3, 4-13, 5-2, 5-26, 5-29, 5-76, 5-128, 5-131, 5-133, 5-134, 5-143, 5-151, 5-156, 5-177, 5-201, 6-1, 6-2, 6-27, 6-51, 6-52, 6-53, 6-55, 6-56, 6-58, 6-64, 6-68, 6-76, 6-77, 6-79, 6-81, 6-89, 6-93, 7-1, 7-2, 7-3, 7-5, 7-6, 7-8, 7-13, 7-18, 7-26, 7-27, 7-28, 7-30, 7-31, 7-33, 7-43, 7-51, 7-52, 7-53, 7-55, 7-56, 7-58, 7-63, 7-68, 7-76, 7-77, 7-78, 7-80, 7-88, 7-93, 8-1, 8-2, 8-26 and 8-27.

[0379] The soil treatment herbicidal activity test results show that the compounds of formula I generally have good control effect on broadleaf weeds. Some of the tested compounds have good control effect on broadleaf weeds at the application dose of 75 g a.i. / hm 2The following compounds have excellent control effect on Digitaria horizontalis, and the control effect is not less than 80%. For example, compounds 2-1, 2-43, 2-26, 3-51, 3-127, 4-27, 5-76, 5-126, 5-127, 5-128, 5-131, 5-133, 5-143, 5-151, 5-152, 5-156, 5-177, 5-201, 6-51, 6-52, 6-53, 6-55, 6-56, 6-58, 6-64, 6-68, 6-76, 6-77, 6-79, 6-81, 6-89, 6-93, 7-1, 7-2, 7-3, 7-5, 7-6, 7-8, 7-13, 7-18, 7-26, 7-27, 7-28, 7-30, 7-31, 7-33, 7-43, 7-51, 7-53, 7-55, 7-56, 7-58, 7-63, 7-68, 7-76, 7-77, 7-78, 7-80, 7-88, 8-1, 8-2, 8-26 and 8-27.

[0380] The results of the soil treatment herbicidal activity test show that the compounds of formula I generally have good control effect on Gramineae weeds. Some of the tested compounds have good control effect on Gramineae weeds at the application dose of 75 g a.i. / hm 2 The following compounds have good control effect on Digitaria horizontalis, and the control effect is not less than 60%. For example, compounds 2-1, 3-1, 3-102, 3-127, 3-176, 4-27, 5-2, 5-27, 5-126, 5-127, 5-128, 5-131, 5-133, 5-134, 5-143, 5-151, 5-156, 5-177, 6-1, 6-2, 6-27, 6-51, 6-52, 6-53, 6-55, 6-56, 6-58, 6-64, 6-68, 6-76, 6-77, 6-79, 6-81, 6-89, 6-93, 7-3, 7-5, 7-6, 7-13, 7-18, 7-26, 7-27, 7-28, 7-30, 7-31, 7-33, 7-43, 7-58, 7-68, 7-78, 7-80, 7-88, 7-93, 8-1, 8-2, 8-26 and 8-27.

[0381] The results of the soil treatment herbicidal activity test show that the compounds of formula I generally have good control effect on Gramineae weeds. Some of the tested compounds have good control effect on Gramineae weeds at the application dose of 75 g a.i. / hm 2The following compounds have good control effect on barnyard grass, and the control effect is not less than 60%. For example, compounds 3-101, 3-102, 3-127, 5-126, 5-127, 5-128, 5-131, 5-133, 5-151, 5-156, 6-53, 6-56, 6-58, 6-64, 6-68, 6-81, 6-89, 6-93, 8-1, 8-2, 8-26 and 8-27.

[0382] The soil treatment herbicidal activity test results show that the compounds of Formula I generally have good control effect on grass weeds. Some of the tested compounds have good control effect on grass weeds at the application dose of 75 g a.i. / hm 2 The following compounds have good control effect on barnyard grass, and the control effect is not less than 60%. For example, compounds 3-101, 3-102, 3-127, 5-126, 5-127, 5-128, 5-131, 5-133, 5-151, 5-156, 6-53, 6-56, 6-58, 6-64, 6-68, 6-81, 6-89, 6-93, 8-1, 8-2, 8-26 and 8-27.

[0383] The soil treatment herbicidal activity test results show that the compounds of Formula I generally have good control effect on grass weeds. Some of the tested compounds have good control effect on grass weeds at the application dose of 75 g a.i. / hm 2The compounds have good control effect on Euphorbia humifusa, and the control effect is not less than 80%. For example, compounds 2-1, 2-2, 2-43, 2-26, 3-127, 3-152, 3-176, 5-1, 5-2, 5-8, 5-26, 5-27, 5-29, 5-51, 5-76, 5-126, 5-127, 5-128, 5-131, 5-133, 5-134, 5-143, 5-151, 5-156, 5-177, 5-201, 6-51, 6-52, 6-53, 6-55, 6-56, 6-58, 6-64, 6-68, 6-76, 6-77, 6-79, 6-81, 6-89, 6-93, 7-1, 7-2, 7-3, 7-5, 7-6, 7-8, 7-13, 7-18, 7-26, 7-27, 7-28, 7-30, 7-31, 7-33, 7-43, 7-51, 7-52, 7-53, 7-55, 7-56, 7-58, 7-63, 7-68, 7-76, 7-77, 7-78, 7-80, 7-88, 7-93, 8-1, 8-2, 8-26 and 8-27.

[0384] Example 12: Test of crop safety

[0385] Stem and leaf activity test: Wheat, rice, corn, cotton, soybean seeds were respectively sowed in a 5cm diameter plastic cup containing nutrient soil, covered with 1cm soil after sowing, flattened, sucked water from the bottom of the plastic cup, and kept the soil moist, placed in the greenhouse and cultured according to the conventional method, and after the test crops grew to 2-3 leaf stage, stem and leaf spray treatment was carried out.

[0386] Soil activity test: the sowing method was the same as the stem and leaf activity test, and soil spray treatment was carried out 24h after sowing.

[0387] Test and phytotoxicity evaluation method: the technical material was dissolved with N,N-dimethylformamide solvent, and then the required concentration of test solution was prepared with 0.1% Tween 80 water according to the test requirements. According to the test design dose, spray treatment was carried out on 3WP-2000 walking type spray tower (manufactured by Nanjing Agricultural Machinery Institute) (spray pressure 0.3MPa, spray liquid amount 45mL / m 2 , nozzle type TP6501E, spray height 300mm, nozzle walking speed 320mm / s), and the test was designed with 3 replicates. After the test materials were treated with the pesticide, the liquid was naturally dried, then transferred to the greenhouse and cultured according to the conventional method, the crop reaction symptoms were observed and recorded regularly, and the phytotoxicity of the test pesticide to the crops was investigated 14 days after the treatment, and the phytotoxicity grade was used for grading:

[0388] Phytotoxicity grade "0" means that the growth inhibition rate or mortality rate of the crops is 0, and there is no phytotoxicity.

[0389] The phytotoxicity grade is "1", indicating that the growth inhibition rate or lethal rate of the crops is 1-20%, and the phytotoxicity is slight;

[0390] The phytotoxicity grade is "2", indicating that the growth inhibition rate or lethal rate of the crops is 21-30%, and the phytotoxicity is moderate;

[0391] The phytotoxicity grade is "3", indicating that the growth inhibition rate or lethal rate of the crops is 31-40%, and the phytotoxicity is relatively heavy;

[0392] The phytotoxicity grade is "4", indicating that the growth inhibition rate or lethal rate of the crops is 41-50%, and the phytotoxicity is heavy;

[0393] The phytotoxicity grade is "5", indicating that the growth inhibition rate or lethal rate of the crops is greater than 50%, and the phytotoxicity is serious.

[0394] The crop names in Chinese, English and Latin used in the test are as follows:

[0395] Wheat (Triticum aestivum);

[0396] Rice (Oryza sativa);

[0397] Corn (Zea mays);

[0398] Cotton (Gossypium herbaceum);

[0399] Soybean (Glycine max);

[0400] The results of the foliage treatment crop safety test show that the compounds of formula I generally have good safety to wheat. Some of the tested compounds have a growth inhibition rate of 0-20% at a dosage of 75 g a.i. / hm 2 The phytotoxicity grade to wheat is not more than 1, and there is no phytotoxicity or slight phytotoxicity. For example, compounds 3-127 and 5-126.

[0401] The results of the foliage treatment crop safety test show that the compounds of formula I generally have good safety to rice. Some of the tested compounds have a growth inhibition rate of 0-20% at a dosage of 75 g a.i. / hm 2 The phytotoxicity grade to rice is not more than 1, and there is no phytotoxicity or slight phytotoxicity. For example, compounds 3-127, 5-126, 5-127 and 6-52.

[0402] The results of the foliage treatment crop safety test show that the compounds of formula I generally have good safety to corn. Some of the tested compounds have a growth inhibition rate of 0-20% at a dosage of 75 g a.i. / hm 2The phytotoxicity grade to corn is not more than 1, no phytotoxicity or slight phytotoxicity. For example, compounds 3-127 and 5-126.

[0403] The soil treatment crop safety test results show that the compounds of formula I generally have good safety to wheat. Some of the tested compounds have good safety to wheat at the application dose of 75 g a.i. / hm 2 The phytotoxicity grade to wheat is not more than 1, no phytotoxicity or slight phytotoxicity. For example, compounds 5-126, 5-127, 6-51, 6-52 and 6-53.

[0404] The soil treatment crop safety test results show that the compounds of formula I generally have good safety to corn. Some of the tested compounds have good safety to corn at the application dose of 75 g a.i. / hm 2 The phytotoxicity grade to corn is not more than 1, no phytotoxicity or slight phytotoxicity. For example, compounds 3-127, 5-126, 5-127, 6-51, 6-52 and 6-53.

[0405] The soil treatment crop safety test results show that the compounds of formula I generally have good safety to soybean. Some of the tested compounds have good safety to soybean at the application dose of 75 g a.i. / hm 2 The phytotoxicity grade to soybean is not more than 1, no phytotoxicity or slight phytotoxicity. For example, compounds 5-126 and 5-127.

[0406] Example 13: Parallel test of indoor weed activity

[0407] According to the above test method, some of the compounds of formula I and the patent control compound KC1 (the compound No. 57 in Table 1 of the patent EP83055A2 specification) were selected for parallel test of the indoor weed control activity in the greenhouse. The application dose of the weed control activity test was 18.75 g a.i. / hm 2 , and the test results are shown in Table 9 and Table 10.

[0408] Table 9: Parallel test results of weed control activity of some compounds of formula I and KC1 (stem-leaf treatment, 14 d after treatment)

[0409]

[0410]

[0411] Table 10: Parallel test results of weed control activity of some compounds of formula I and KC1 (soil treatment, 14 d after treatment)

[0412] Compound Amaranth Epiphyllum Solanum nigrum Crispfingered Cyperus Euphorbia Commelina benghalensis Commelina diffusa 5-128 80 100 100 80 90 90 6-51 70 100 100 100 100 90 6-53 100 100 100 90 100 100 6-56 100 100 100 100 100 100 6-58 100 100 100 90 100 100 6-64 100 100 100 100 90 90 6-68 70 100 100 80 90 90 6-79 80 100 100 80 80 90 6-81 100 100 100 90 100 100 6-89 90 100 100 90 100 90 6-93 70 100 100 90 100 90 7-68 100 100 100 60 90 100 7-78 100 90 100 60 100 100 KC1 30 0 50 0 0 0

[0413] From the parallel comparison data in Table 9 and Table 10, it can be found that the compounds of the present application have good weed control activity at the application dose of 18.75 g a.i. / hm2 The compounds of the present application have excellent herbicidal effect at the dosage of 75 g a.i. / hm

[0414] Example 14: Parallel test of herbicidal activity and crop safety

[0415] According to the above test method, some compounds of formula I and the patent control compound KC2 (the compound of Example 1 in the specification of patent WO2016120116A1) were selected to carry out parallel tests of greenhouse herbicidal activity and crop safety. The herbicidal activity was expressed by 0-100%, and the phytotoxicity of crops was graded by phytotoxicity grade. The test results are shown in Table 11.

[0416] Table 11: Parallel test results of herbicidal activity and crop safety of some compounds of formula I and KC2 (foliar treatment, 14 days after treatment. " / " means not tested)

[0417]

[0418]

[0419] From the parallel comparison data in Table 11, it can be found that the compounds of the present application have safety to crops. The compound 5-126 of the present application as a representative compound has excellent herbicidal effect on most weeds at the foliar treatment dosage of 75 g a.i. / hm 2 and has good safety to wheat, corn and rice, and its crop safety is obviously better than the control compound KC2 (the compound of Example 1 in the specification of patent WO2016120116A1).

Claims

1. A tetrasubstituted benzoate compound containing an alkoxyacetic acid ester substituent, characterized in that... Tetrasubstituted benzoate compounds containing alkoxyacetic acid ester substituents have the structure shown in Formula I: ； I in: X is selected from hydrogen, fluorine, or chlorine; Y is selected from fluorine or chlorine; Ak is selected from C1-C6 alkyl, phenyl, or 2,4-dichlorophenyl; R is selected from C1~C6 alkyl, C2~C8 alkenyl, C1~C6 haloalkyl, C3~C8 cycloalkyl, and C1~C6 alkyl. Het is selected from ； R4 and R6 are selected from hydrogen or methyl.

2. The tetrasubstituted benzoate compound containing an alkoxyacetic acid ester substituent according to claim 1, characterized in that, In Formula I: X is selected from hydrogen, fluorine, or chlorine; Y is selected from chlorine; Ak is selected from C1-C6 alkyl, phenyl, or 2,4-dichlorophenyl; R is selected from C1~C6 alkyl, C2~C8 alkenyl, C1~C6 haloalkyl, C3~C8 cycloalkyl, and C1~C6 alkyl. Het is selected from Het8.

3. The tetrasubstituted benzoate compound containing an alkoxyacetic acid ester substituent according to claim 1, characterized in that, In Formula I: X is selected from hydrogen, fluorine, or chlorine; Y is selected from chlorine; Ak is selected from methyl, ethyl, phenyl, or 2,4-dichlorophenyl; R is selected from methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, n-pentyl, isopentyl, n-hexyl, allyl, trifluoromethyl, 2-fluoroethyl, 2,2,2-trifluoroethyl, 2-chloroethyl, 3-chloron-propyl, 4-chloron-butyl, or cyclopropylmethyl; Het is selected from Het6 and Het 10 Het 11 Or Het 14 In this context, R4 and R6 are selected from hydrogen or methyl.

4. The tetrasubstituted benzoate compound containing an alkoxyacetic acid ester substituent according to claim 1, characterized in that, The tetrasubstituted benzoate compound containing the alkoxyacetic acid ester substituent is selected from any one of the following compounds: 2-Chloro-4-fluoro-5-(5-tert-butyl-2-oxo-1,3,4-oxadiazol-3(2H)-yl)benzoic acid (1-methoxy-1-n-pentoxycarbonylmethyl) ester (compounds 4-6); 2-Chloro-4-fluoro-5-(5-tert-butyl-2-oxo-1,3,4-oxadiazol-3(2H)-yl)benzoic acid (1-ethoxy-1-n-propoxycarbonylmethyl) ester (compound 4-28); 2-Chloro-5-(3,5-dimethyl-2,6-oxo-4-thio-1,3,5-triazin-1-yl)benzoic acid (1-ethoxy-1-isopropoxycarbonylmethyl) ester (compound 5-29). 2-Chloro-4-fluoro-5-(3,5-dimethyl-2,6-oxo-4-thio-1,3,5-triazin-1-yl)benzoic acid (1-methoxy-1-methoxycarbonylmethyl) ester (compound 5-126). 2-Chloro-4-fluoro-5-(3,5-dimethyl-2,6-oxo-4-thio-1,3,5-triazin-1-yl)benzoic acid (1-methoxy-1-allyloxycarbonylmethyl) ester (compound 5-134). 2-Chloro-4-fluoro-5-(3,5-dimethyl-2,6-oxo-4-thio-1,3,5-triazin-1-yl)benzoic acid (1-methoxy-1-cyclopropylmethoxycarbonylmethyl) ester (compound 5-143); 2-Chloro-5-(3-methyl-2,6-dioxo-4-trifluoromethyl-3,6-dihydropyrimidin-1(2H)-yl)benzoic acid (1-ethoxy-1-ethoxycarbonylmethyl) ester (compound 6-27); 2-Chloro-4-fluoro-5-(3-methyl-2,6-dioxo-4-trifluoromethyl-3,6-dihydropyrimidin-1(2H)-yl)benzoic acid (1-methoxy-1-methoxycarbonylmethyl) ester (compound 6-51); 2-Chloro-4-fluoro-5-(3-methyl-2,6-dioxo-4-trifluoromethyl-3,6-dihydropyrimidin-1(2H)-yl)benzoic acid (1-methoxy-1-n-propoxycarbonylmethyl) ester (compounds 6-53); 2-Chloro-4-fluoro-5-(3-methyl-2,6-dioxo-4-trifluoromethyl-3,6-dihydropyrimidin-1(2H)-yl)benzoic acid (1-methoxy-1-(3-chloropropoxy)carbonylmethyl) ester (compounds 6-64); 2-Chloro-4-fluoro-5-(3-methyl-2,6-dioxo-4-trifluoromethyl-3,6-dihydropyrimidin-1(2H)-yl)benzoic acid (1-methoxy-1-cyclopropylmethoxycarbonylmethyl) ester (compounds 6-68); 2-Chloro-4-fluoro-5-(4-trifluoromethyl-6-oxopyridazin-1(6H)-yl)benzoic acid (1-methoxy-1-n-hexyloxycarbonylmethyl) ester (compounds 7-8); 2-Chloro-4-fluoro-5-(4-trifluoromethyl-6-oxopyridazin-1(6H)-yl)benzoic acid (1-methoxy-1-(2-chloroethoxy)carbonylmethyl) ester (compounds 7-13); 2-Chloro-4-fluoro-5-(4-trifluoromethyl-6-oxopyridazin-1(6H)-yl)benzoic acid (1-ethoxy-1-n-propoxycarbonylmethyl) ester (compound 7-28); 2-Chloro-4-fluoro-5-(5-methyl-6-oxo-4-trifluoromethylpyridazine-1(6H)-yl)benzoic acid (1-methoxy-1-n-pentoxycarbonylmethyl) ester (compounds 7-56); 2-Chloro-4-fluoro-5-(5-methyl-6-oxo-4-trifluoromethylpyridazine-1(6H)-yl)benzoic acid (1-ethoxy-1-(2-chloroethoxy)carbonylmethyl) ester (compounds 7-88); 2-Chloro-4-fluoro-5-(3-chloro-5-(trifluoromethyl)pyridin-2-yl)benzoic acid (1-methoxy-2-ethoxycarbonylmethyl) ester (compound 8-2).

5. The use of any one of the tetrasubstituted benzoate compounds containing alkoxyacetic acid ester substituents in weed control according to claims 1-4.

6. A herbicidal composition, characterized in that: The herbicidal composition is an active substance and an agriculturally acceptable carrier, wherein the active component is a tetrasubstituted benzene compound containing an alkoxyacetic acid ester substituent as described in any one of claims 1-4, and the weight percentage of the active component in the composition is 1% to 99%.

7. A method for controlling weeds, characterized in that: Applying a herbicidal effective dose of a tetrasubstituted benzene compound containing an alkoxyacetic acid ester substituent as described in any one of claims 1-4, or a herbicidal composition as described in claim 6, to weeds or the weed growing medium or site.

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