Benzothiazole compounds, their synthesis and applications

Abstract

This invention provides a benzothiazole compound as shown in formula (I). The invention further provides a method for synthesizing this type of compound, as well as the synthesis of important intermediates used in the preparation method. The benzothiazole compound exhibits excellent herbicidal activity and is safe for major field crops such as winter wheat, corn, and rice, and can be used as a herbicide or processed into herbicidal compositions.

Description

Technical Field

[0001] This invention belongs to the field of chemical synthesis technology, specifically relating to a class of 3,6-disubstituted benzothiazole compounds, their preparation methods, compositions, and their use as herbicides. Background Technology

[0002] Weeds are a major factor leading to crop yield reduction, and the use of chemical herbicides is the primary technical means of weed control. With the widespread use of herbicides, weeds are becoming increasingly resistant to existing chemical herbicides, and the management of resistant weeds has become a critical problem that urgently needs to be solved in agricultural production. Developing herbicides with novel chemical structures and mechanisms of action is the fundamental way to solve this problem.

[0003] Benzothiazole derivatives possess a wide range of biological activities. Among the commercially available herbicides, benzothiazole derivatives include bensulfuron-methyl, chlorpyrifos, bensulfuron-methyl, and haloxyfop-methyl. These commercially available herbicides play an important role in weed control.

[0004]

[0005] The present invention aims to design and synthesize a novel class of 3,6-disubstituted benzothiazole compounds and to explore the herbicidal activity of 3,6-disubstituted benzothiazole compounds. Summary of the Invention

[0006] The purpose of this invention is to provide the general structural formula, synthetic method, and use as a herbicidal active ingredient of 3,6-disubstituted benzothiazole compounds. These 3,6-disubstituted benzothiazole compounds possess a novel molecular skeleton, exhibit excellent herbicidal activity against a variety of broadleaf weeds and some grass weeds, and demonstrate good crop safety for crops such as rice, wheat, and corn.

[0007] In the semantic expression of this invention, 3,6-disubstituted benzothiazole compounds and benzothiazole compounds have the same meaning.

[0008] A benzothiazole compound having the chemical structural formula shown in formula (I).

[0009]

[0010] In formula (I):

[0011] Substituent R 1 Selected from halogen or C 1～ C4 haloalkyl.

[0012] Substituent R 2 Selected from hydrogen, halogen or C 1～ C4 haloalkyl.

[0013] Substituent R 3 Selected from C 1～ C8 alkyl, C 1～ C8 haloalkyl, C 3～ C6 alkenyl, halogenated C 3～ C6 alkenyl, C 3～ C6 alkynyl, halogenated C 3～ C6 alkynyl, cyano C 1～ C8 alkyl, C 1～ C8 alkyloxy, C 1～ C8 haloalkyloxy group, C 1～ C8 alkyl thio group, C 1～ C8 alkyloxy-C 1～ C8 alkyl, hydrogen, CN.

[0014] Substituent R 4 Selected from

[0015]

[0016] As a substituent R 4 Further explanation, in which,

[0017] Substituent R 5 Selected from hydrogen, C 1～ C6 alkyl, C 3～ C6 alkenyl, C 3～ C6 ynyl group, C 1～ C6 haloalkyl, C 3～ C6 haloalkenyl, C 3～ C6 haloalkynyl group, C 1～ C6 alkyl carbonyl, phenyl-C 1～ C6 alkyl carbonyl, C 1～ C6 alkoxycarbonyl, phenoxycarbonyl, phenyl-C 1～ C6 alkoxycarbonyl, cyano C 1～ C6 alkyl, C 1～ C6 alkoxy-C 1～ C6 alkyl, C 1～ C6 alkoxy-C 1～ C6 alkoxy-C 1～ C6 alkyl, di(C 1～ C6 alkoxy)C 1～ C6 alkyl, C 1～ C6 haloalkoxy-C 1～ C6 alkyl, C 3～ C6 alkenyloxy-C 1～ C6 alkyl, C 3～ C6 haloalkenyloxy-C 1～ C6 alkyl, C 3～ C6 alkenyloxy-C1～ C6 alkoxy-C 1～ C6 alkyl, C 1～ C6 alkylthio-C 1～ C6 alkyl, C 1～ C6 alkylsulfinyl-C 1～ C6 alkyl, C 1～ C6 alkylsulfonyl-C 1～ C6 alkyl, C 1～ C6 alkyl carbonyl-C 1～ C6 alkyl, C 1～ C6 alkylcarbonyloxy-C 1～ C6 alkyl, C 1～ C6 alkoxycarbonyl-C 1～ C6 alkyl, C 1～ C6 alkoxycarbonyl-C 1～ C6 alkyl, C 1～ C6 alkoxycarbonyl-C 3～ C6 alkenyl, C 1～ C6 alkoxycarbonyl-halogenated C 3～ C6 alkenyl, C 1～ C6 haloalkoxycarbonyl-C 1～ C6 alkyl, C 3～ C6 chain olefin carbonyl-C 1～ C6 alkyl, C 3～ C6 alkynyloxycarbonyl-C 1～ C6 alkyl, C 1～ C6 alkylamine-C 1～ C6 alkyl, C 1～ C6 alkylamine carbonyl-C 1～ C6 alkyl, di-C 1～ C6 alkylamine-C 1～ C6 alkyl, C 3～ C6 cycloalkyl-C 1～ C6 alkyl, phenyl, phenyl-C 1～ C4 alkyl, 5-6 membered heterocyclic -C 1～ C6 alkyl.

[0018] Or R 5 Selected from -CH2-CH2-ON=CR 11 R 12 -CH2-CH2-N=CR 13 R 14 -CH2-CH2-NH-C(CH3)=CR 15 R 16 -N = CR 11 R 12 , where R 11 R 12 R 13R 14 R 15 and R 16 Selected independently from hydrogen and C 1～ C4 alkyl, CN, -C(=O)OC 1～ C4 alkyl, phenyl, or substituted phenyl.

[0019] Substituent R 6 and R 7 R is independent of each other. 5 , or R 6 and R 7 It forms 5- to 7-membered carbon rings.

[0020] Substituent R 8 Selected from hydrogen, C 1～ C4 alkyl, C 3～ C6 alkenyl, C 3～ C6 ynyl group, C 1～ C6 haloalkyl, C 3～ C6 haloalkenyl, C 3～ C6-haloacetyl group.

[0021] Substituent R 9 Selected from C 1～ C6 alkyl, C 1～ C6 alkoxy, phenyl, phenoxy, phenyl-C 1～ C4 alkyl, phenyl-C 1～ C4 alkoxy group. The benzene ring may contain 1 to 4 alkoxy groups selected from R. 17 Substituents. Regarding substituent R... 17 For a further explanation of preferred embodiments, please refer to the description.

[0022] Substituent R 10 Selected from hydrogen, C 1～ C6 alkyl, C 1～ C6 haloalkyl, C 3～ C6 cycloalkyl, C 3～ C6 halocycloalkyl, phenyl, phenyl-C 1～ C4 alkyl group. The benzene ring may contain 1 to 4 alkyl groups selected from R. 17 Substituents. Regarding substituent R... 17 For a further explanation of preferred embodiments, please refer to the description.

[0023] As a preferred embodiment of the present invention, the substituent R 1 Selected from halogen or C 1～ C2 haloalkyl. Particularly preferred, R 1 Selected from fluorine, chlorine, bromine, iodine, trifluoromethyl, difluoromethyl, or chlorodifluoromethyl. More preferably, R 1 Selected from fluorine, chlorine, bromine, or trifluoromethyl. Most preferably, R1 Selected from trifluoromethyl.

[0024] As a preferred embodiment of the present invention, the substituent R 2 Selected from hydrogen, halogen or C 1～ C4 haloalkyl. Particularly preferred, R 2 Selected from hydrogen, fluorine, chlorine, bromine, iodine, trifluoromethyl, difluoromethyl, or chlorodifluoromethyl. More preferably, R 2 Selected from hydrogen, fluorine, chlorine, bromine, and trifluoromethyl. Most preferably, R 2 Selected from hydrogen, fluorine, or chlorine.

[0025] As a preferred embodiment of the present invention, the substituent R 3 Selected from C 1～ C8 alkyl, C 1～ C8 haloalkyl, C 3～ C6 alkenyl, C 3～ C6 alkynyl, halogenated C 3～ C6 alkenyl, halogenated C 3～ C6 alkynyl, cyano C 1～ C8 alkyl, hydrogen, or CN.

[0026] Substituent R 3 Particularly preferred, R 3 Selected from methyl, ethyl, n-propyl, n-butyl, n-pentyl, n-hexyl, n-heptyl, n-octyl, 1-propenyl, 2-propenyl, 1-butenyl, 2-butenyl, 3-butenyl, 1-pentenyl, 2-pentenyl, 3-pentenyl, 4-pentenyl, 1-hexenyl, 2-hexenyl, 3-hexenyl, 4-hexenyl, 5-hexenyl.

[0027] Substituent R 3 More preferably, R 3 Selected from methyl, ethyl, n-propyl, n-butyl, n-pentyl, n-hexyl, n-heptyl, n-octyl, 1-propenyl, 1-butenyl, 1-pentenyl, and 1-hexenyl. Most preferably, R 3 Selected from methyl, ethyl, n-propyl, n-butyl, n-pentyl, n-hexyl, and n-heptyl.

[0028] As a preferred embodiment of the present invention, the substituent R 5 Selected from hydrogen, C 1～ C4 alkyl, C 3～ C6 alkenyl, C 3～ C6 ynyl group, C 1～ C4 haloalkyl, C 3～ C6 haloalkenyl, C 3～ C6 haloalkynyl, cyanoC 1～ C4 alkyl, C 1～ C4 alkoxy-C 1～C3 alkyl, C 1～ C3 alkoxy-C 1～ C3 alkoxy-C 1～ C3 alkyl, di(C 1～ C3alkoxy)C 1～ C3 alkyl, C 1～ C4 haloalkoxy-C 1～ C3 alkyl, C 3～ C6 alkenyloxy-C 1～ C3 alkyl, C 3～ C6 haloalkenyloxy-C 1～ C3 alkyl, C 3～ C6 alkenyloxy-C 1～ C3 alkoxy-C 1～ C3 alkyl, C 1～ C3 alkylthio-C 1～ C3 alkyl, C 1～ C3 alkylsulfinyl-C 1～ C3 alkyl, C 1～ C3 alkylsulfonyl-C 1～ C3 alkyl, C 1～ C3 alkyl carbonyl-C 1～ C3 alkyl, C 1～ C3alkylcarbonyloxy-C 1～ C3 alkyl, C 1～ C3 alkoxycarbonyloxy-C 1～ C3 alkyl, C 1～ C3 alkoxycarbonyl-C 1～ C3 alkyl, C 1～ C3 alkoxycarbonyl-C 3～ C6 alkenyl, C 1～ C3 alkoxycarbonyl-halogenated C 3～ C6 alkenyl, C 1～ C3 haloalkoxycarbonyl-C 1～ C3 alkyl, C 3～ C6 chain olefin carbonyl-C 1～ C3 alkyl, C 3～ C6 alkynyloxycarbonyl-C 1～ C3 alkyl, C 1～ C3 alkylamine-C 1～ C3 alkyl, di-C 1～ C3 alkylamine-C 1～ C3 alkyl, C 3～ C6 cycloalkylmethyl, C 3～ C6 cycloalkyl ethyl, phenyl, benzyl, 5-6 membered heterocyclic methyl, 5-6 membered heterocyclic ethyl.

[0029] As a preferred embodiment of the present invention, R 5Selected from -CH2-CH2-ON=CR 11 R 12 -CH2-CH2-N=CR 13 R 14 -CH2-CH2-NH-C(CH3)=CR 15 R 16 -N = CR 11 R 12 , where R 11 R 12 R 13 R 14 R 15 and R 16 Selected independently from hydrogen and C 1～ C4 alkyl, CN, -C(=O)OC 1～ C4 alkyl. Preferably, the R 11 R 12 R 13 R 14 R 15 and R 16 The following can be selected independently: hydrogen, methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, CN, -C(=O)O-methyl, -C(=O)O-ethyl, -C(=O)O-isopropyl, phenyl, methylphenyl, or halophenyl.

[0030] As a preferred embodiment of the present invention, the substituent R 5 Selected from C 3～ C6 cycloalkylmethyl, C 3～ C6 cycloalkyl ethyl, phenyl, benzyl, wherein the cycloalkyl or benzene ring contains or does not contain 1 to 4 radicals selected from R 17 Substituents.

[0031] As a substituent R 17 Further explanation, substituent R 17 Selected from halogens, C 1～ C6 alkyl, C 1～ C6 haloalkyl, C 3～ C6 cycloalkyl, C 1～ C6 alkyl carbonyl, C 1～ C6 haloalkyl carbonyl, C 3～ C6 cycloalkoxy, C 1～ C6 alkoxy, C 1～ C6 haloalkoxy group, C 1～ C6 alkoxycarbonyl, C 1～ C6 haloalkoxycarbonyl, C 3～ C6 haloalkenyl, C 3～ C6 alkenyloxy group, C 1～ C6 alkylthio group, C1～ C6 alkyl sulfinyl group, C 1～ C6 alkylsulfonyl, C 1～ C6 alkoxysulfonyl, C 1～ C6 alkylsulfonyloxy, C 1～ C6 alkoxycarbonyl-C 1～ C6 alkoxy,

[0032] As a preferred embodiment of the present invention, the substituent R 5 Selected from C 3～ C6 cycloalkylmethyl, C 3～ C6 cycloalkyl ethyl, phenyl, benzyl, wherein the cycloalkyl, phenyl, and benzyl rings contain or do not contain 1 to 4 groups selected from R 17 Substituents.

[0033] Preferably, the substituent R 17 Selected from halogens, C 1～ C3 alkyl, C 1～ C3 haloalkyl, C 3～ C6 cycloalkyl, C 3～ C6 cycloalkoxy, C 1～ C3 alkoxy, C 1～ C3 haloalkoxy group, C 3～ C6 haloalkenyl, C 3～ C6 alkenyloxy group, C 1～ C3 alkylthio group, C 1～ C3 alkoxycarbonyl-C 1～ C3 alkoxy, Particularly preferred, the R 17 Selected from fluorine, chlorine, bromine, methyl, ethyl, isopropyl, methoxy, ethoxy, More preferably, the R 17 Selected from fluorine, chlorine, bromine, methyl, ethyl, isopropyl,

[0034] As a preferred embodiment of the present invention, the substituent R 5 Selected from 5- to 6-membered heterocyclic methyl groups and 5- to 6-membered heterocyclic ethyl groups, wherein the atoms constituting the heterocycle, in addition to carbon atoms, also have one or two atoms selected from -N(R) 18 The heterocycle contains or contains 1 to 4 ring members selected from R-, -N=N-, -O-, and -S-, wherein the heterocycle does not contain or contains 1 to 4 ring members selected from R-. 19 Substituents.

[0035] As a substituent R 18 Further explanation, R 18 Selected from hydrogen, C 1～ C4 alkyl, CN, -C(=O)OC 1～C4 alkyl. Preferably, R 18 Selected from hydrogen, methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, and CN.

[0036] As a substituent R 19 Further explanation, R 19 Selected from halogens, nitro groups, CN, and C. 1～ C4 alkyl, C 1～ C4 haloalkyl, C 1～ C4 alkoxy, C 1～ C4 alkoxycarbonyl. Preferably, R 19 Selected from fluorine, chlorine, bromine, iodine, nitro, CN, methyl, ethyl, propyl, butyl, isopropyl, isobutyl, chloromethyl, chloroethyl, chloropropyl, methoxy, ethoxy, propyloxy, butyloxy, ethoxycarbonyl, propoxycarbonyl, and butyloxycarbonyl.

[0037] As a preferred embodiment of the present invention, the R 6 and R 7 A 5- to 7-membered carbon ring is formed, wherein the atoms constituting the 5- to 7-membered carbon ring, in addition to carbon atoms, also have one or two atoms selected from -N(R) 18 The ring members are -N=N-, -C(=O)-, -O-, and -S-. The 5- to 7-membered carbon rings may or may not contain 1 to 4 rings selected from R-. 19 Substituents are substituted.

[0038] In this preferred embodiment, R 18 Selected from hydrogen, C 1～ C4 alkyl, CN, -C(=O)OC 1～ C4 alkyl. More preferably, R 18 Selected from hydrogen, methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, and CN.

[0039] In this preferred embodiment, R 19 Selected from halogens, nitro groups, CN, and C. 1～ C4 alkyl, C 1～ C4 haloalkyl, C 1～ C4 alkoxy, C 1～ C4 alkoxycarbonyl. More preferably, R 19 Selected from fluorine, chlorine, bromine, iodine, nitro, CN, methyl, ethyl, propyl, butyl, isopropyl, isobutyl, chloromethyl, chloroethyl, chloropropyl, methoxy, ethoxy, propyloxy, butyloxy, ethoxycarbonyl, propoxycarbonyl, and butyloxycarbonyl.

[0040] As a preferred embodiment of the present invention, the R 8Selected from hydrogen, methyl, ethyl, propyl, butyl, isopropyl, isobutyl, allyl, propyne, chloroethyl, chloropropyl, acetyl, propionyl, benzylacetyl, methoxycarbonyl, phenoxycarbonyl, and benzyloxyacyl.

[0041] As a preferred embodiment of the present invention, the R 9 Selected from C 1～ C3 alkyl, C 1～ C3 alkoxy, phenyl, phenoxy, benzyl, phenethyl, benzyloxy, phenethyloxy. The R 9 The benzene ring may contain 1 to 4 molecules selected from R 17 Substituents. Particularly preferably, the R 9 Selected from methyl, ethyl, methoxy, ethoxy, phenyl, phenoxy, benzyl, phenethyl, benzyloxy, and phenethyloxy.

[0042] In the substituent R 9 In the preferred embodiment, R 17 Selected from halogens, C 1～ C6 alkyl, C 1～ C6 haloalkyl, C 3～ C6 cycloalkyl, C 1～ C6 alkyl carbonyl, C 1～ C6 haloalkyl carbonyl, C 3～ C6 cycloalkoxy, C 1～ C6 alkoxy, C 1～ C6 haloalkoxy group, C 1～ C6 alkoxycarbonyl, C 1～ C6 haloalkoxycarbonyl, C 3～ C6 haloalkenyl, C 3～ C6 alkenyloxy group, C 1～ C6 alkylthio group, C 1～ C6 alkyl sulfinyl group, C 1～ C6 alkylsulfonyl, C 1～ C6 alkoxysulfonyl, C 1～ C6 alkylsulfonyloxy, C 1～ C6 alkoxycarbonyl-C 1～ C6 alkoxy, Particularly preferred, the R 17 Selected from C 1～ C3 alkyl, C 1～ C3 haloalkyl, C 3～ C6 cycloalkyl, C 3～ C6 cycloalkoxy, C 1～ C3 alkoxy, C 1～ C3 haloalkoxy group, C 3～ C6 haloalkenyl, C 3～ C6 alkenyloxy group, C1～ C3 alkylthio group, C 1～ C3 alkoxycarbonyl-C 1～ C3 alkoxy, More preferably, R 17 Selected from methyl, ethyl, methoxy, ethoxy,

[0043] As a preferred embodiment of the present invention, the R 10 Selected from hydrogen, C 1～ C6 alkyl, C 1～ C6 haloalkyl, C 3～ C6 cycloalkyl, C 3～ C6 halocycloalkyl, phenyl, phenyl-C 1～ C4 alkyl. Particularly preferred, the R 10 Selected from hydrogen, methyl, ethyl, propyl, butyl, isopropyl, isobutyl, allyl, propyne, chloroethyl, chloropropyl, phenyl, benzyl, phenethyl.

[0044] As a preferred embodiment of the present invention, the R 10 The benzene ring may contain 1 to 4 molecules selected from R 17 Substituents. In substituent R 10 In the preferred embodiment, R 17 Selected from halogens, C 1～ C6 alkyl, C 1～ C6 haloalkyl, C 3～ C6 cycloalkyl, C 1～ C6 alkyl carbonyl, C 1～ C6 haloalkyl carbonyl, C 3～ C6 cycloalkoxy, C 1～ C6 alkoxy, C 1～ C6 haloalkoxy group, C 1～ C6 alkoxycarbonyl, C 1～ C6 haloalkoxycarbonyl, C 3～ C6 haloalkenyl, C 3～ C6 alkenyloxy group, C 1～ C6 alkylthio group, C 1～ C6 alkyl sulfinyl group, C 1～ C6 alkylsulfonyl, C 1～ C6 alkoxysulfonyl, C 1～ C6 alkylsulfonyloxy, C 1～ C6 alkoxycarbonyl-C 1～ C6 alkoxy, Particularly preferred, the R 17 Selected from C 1～ C3 alkyl, C 1～ C3 haloalkyl, C 3～ C6 cycloalkyl, C3～ C6 cycloalkoxy, C 1～ C3 alkoxy, C 1～ C3 haloalkoxy group, C 3～ C6 haloalkenyl, C 3～ C6 alkenyloxy group, C 1～ C3 alkylthio group, C 1～ C3 alkoxycarbonyl-C 1～ C3 alkoxy, More preferably, the R 17 Selected from methyl, ethyl, methoxy, ethoxy,

[0045] This invention further provides salts of benzothiazole compounds. Salts of compounds having the chemical structure shown in formula (I) can be considered conventional derivatives of the benzothiazole compounds described in this invention. If the benzothiazole compounds of this invention have ionizable functional groups (e.g., carboxyl groups), they can be used in the form of salts and have the same technical effects as this invention. The benzothiazole compounds of this invention can be formed into corresponding salts by conventional methods. These salts can be of any form, such as alkali metal salts (e.g., sodium or potassium salts), alkaline earth metal salts (e.g., magnesium or calcium salts), or ammonium salts (e.g., dimethylamine or triethylamine salts).

[0046] This invention further provides isomers of benzothiazole compounds, or derivatives in optically active forms. As a further study of the benzothiazole compounds, those skilled in the art can resolve or separate the stereoisomers of the benzothiazole compounds using conventional techniques. If the benzothiazole compounds of this invention can form geometric isomers, such as E / Z isomers, this invention can also obtain pure isomers and mixtures thereof.

[0047] The benzothiazole compounds of this invention have one or more chiral centers. Compounds having the chemical structure shown in formula (I) exist as enantiomers or diastereomers. Those skilled in the art can obtain pure enantiomers, diastereomers, or mixtures thereof using conventional techniques. In particular, when R... 3 When it is not hydrogen, R 3 and R 4 The attached carbon atom is a chiral carbon, thus the benzothiazole compounds exhibit two optical isomers, R and S. From this perspective, the benzothiazole compounds of this invention comprise all optical isomers and mixtures thereof in any proportion.

[0048] It should be noted that in the benzothiazole compounds represented by formula (I), the substituent R 1 ~R 19The terms used in the definition to describe the structural types of organic compounds are collective terms for each group member. The term halogen, in each case, represents fluorine, chlorine, bromine, and iodine. All hydrocarbon chains, such as all alkyl, alkenyl, alkynyl, and alkoxy chains, can be straight-chain or branched, and are prefixed with C. n～ C m In each case, the number of possible carbon atoms in the group is indicated (m and n are both positive integers). To better understand the present invention, the meaning of some groups is explained by way of example.

[0049] -C 1～ C4 alkyl: methyl, ethyl, n-propyl, isopropyl, n-butyl, CH(CH3)-C2H5, CH2-CH(CH3)2 and C(CH3)3.

[0050] -C 1～ C8 alkyl groups: methyl, ethyl, n-propyl, isopropyl, n-butyl, CH(CH3)-C2H5, CH2-CH(CH3)2, C(CH3)3, n-pentyl, 1-methylbutyl, 2-methylbutyl, 3-methylbutyl, 2,2-dimethylpropyl, 1-ethylpropyl, n-hexyl, 1,1-dimethylpropyl, 1,2-dimethylpropyl, 1-methylpentyl, 2-methylpentyl, -3-methylpentyl, 4-methylpentyl, 1,1-dimethylbutyl, 1,2-dimethylbutyl, 1,3-dimethylbutyl, 2,3-dimethylbutyl, 3,3-dimethylbutyl, 1-ethylbutyl, 2-ethylbutyl, 1,1,2-trimethylpropyl, 1,2,2-trimethylpropyl, 1-ethyl-1-methylpropyl, 1-ethyl-2-methylpropyl Heptyl, 1-methylhexyl, 2-methylhexyl, 3-methylhexyl, 4-methylhexyl, 5-methylhexyl, 1,1-dimethylpentyl, 1,2-dimethylpentyl, 1,3-dimethylpentyl, 1,4-dimethylpentyl, 2,3-dimethylpentyl, 2,4-dimethylpentyl, 3,3-dimethylpentyl, 3,4-dimethylpentyl, 1-ethylpentyl, 2-ethylpentyl, 3-ethylpentyl, 1,1,2-trimethylbutyl, 1,2,2-trimethylbutyl, n-octyl, 1-methylheptyl, 2-methylheptyl, 3-methylheptyl, 4-methylheptyl, 5-methylheptyl, 6-methylheptyl, 1,1-dimethylheptyl, 1,2-dimethylheptyl, 1,3-dimethylheptyl, 1,4-dimethylheptyl, 1,5-dimethylheptyl.

[0051] -C 1～ C4 haloalkyl: Alkyl groups as described above that are partially or wholly substituted with fluorine, chlorine, bromine, and / or iodine. 1～C4 alkyl groups, such as chloromethyl, dichloromethyl, trichloromethyl, fluoromethyl, difluoromethyl, trifluoromethyl, chlorofluoromethyl, dichloromonofluoromethyl, monochlorodifluoromethyl, bromomethyl, iodomethyl, 2-fluoroethyl, 2-chloroethyl, 2-bromoethyl, 2-iodoethyl, 2,2-difluoroethyl, 2,2,2-trifluoroethyl, 2-chloro-2-fluoroethyl, 2-chloro-2,2-difluoroethyl, 2,2-dichloro-2-fluoroethyl, 2,2,2-trichloroethyl, pentafluoroethyl, 2-fluoropropyl, 3-fluoropropyl, 2,2-difluoropropyl 2,3-difluoropropyl, 2-chloropropyl, 3-chloropropyl, 2,3-dichloropropyl, 2-bromopropyl, 3-bromopropyl, 3,3,3-trifluoropropyl, 3,3,3-trichloropropyl, 2,2,3,3,3-pentafluoropropyl, heptafluoropropyl, 1-fluoromethyl-2-fluoroethyl, 1-chloromethyl-2-chloroethyl, 1-bromomethyl-2-bromoethyl, 4-fluorobutyl, 4-chlorobutyl, 4-bromobutyl, nonafluorobutyl, 1,1,2,2-tetrafluoroethyl and 1-trifluoromethyl-1,2,2,2-tetrafluoroethyl.

[0052] -C 1～ C4 alkoxy groups: methoxy, ethoxy, propoxy, 1-methylethoxy, butoxy, 1-methylpropoxy, 2-methylpropoxy, and 1,1-dimethylethoxy.

[0053] -C 1～ C6 alkoxy group: except for -C as described above 1～ In addition to C4 alkoxy, there are also, for example: pentoxy, 1-methylbutoxy, 2-methylbutoxy, 3-methoxybutoxy, 1,1-dimethylpropoxy, 1,2-dimethylpropoxy, 2,2-dimethylpropoxy, 1-ethylpropoxy, hexoxy, 1-methylpentoxy, 2-methylpentoxy, 3-methylpentoxy, 4-methylpentoxy, 1,1-dimethylbutoxy, 1,2-dimethylbutoxy, 1,3-dimethylbutoxy, 2,2-dimethylbutoxy, 2,3-dimethylbutoxy, 3,3-dimethylbutoxy, 1-ethylbutoxy, 2-ethylbutoxy, 1,1,2-trimethylpropoxy, 1,2,2-trimethylpropoxy, 1-ethyl-1-methylpropoxy, and 1-ethyl-2-methylpropoxy.

[0054] -C 1～ C3 haloalkoxy group: -C partially or completely substituted by fluorine, chlorine, bromine and / or iodine. 1～C3 alkoxy groups, such as fluoromethoxy, difluoromethoxy, trifluoromethoxy, monochlorodifluoromethoxy, monobromodifluoromethoxy, 2-fluoroethoxy, 2-chloroethoxy, 2-bromoethoxy, 2-iodoethoxy, 2,2-difluoroethoxy, 2,2,2-trifluoroethoxy, 2-chloro-2-fluoroethoxy, 2-chloro-2,2-difluoroethoxy, 2,2-dichloro-2-fluoroethoxy, 2,2,2-trichloroethoxy, pentafluoroethoxy, 2-fluoro Propoxy, 3-fluoropropoxy, 2-chloropropoxy, 3-chloropropoxy, 2-bromopropoxy, 3-bromopropoxy, 2,2-difluoropropoxy, 2,3-difluoropropoxy, 2,3-dichloropropoxy, 3,3,3-trifluoropropoxy, 3,3,3-trichloropropoxy, 2,2,3,3,3-pentafluoropropoxy, heptafluoropropoxy, 1-fluoromethyl-2-fluoroethoxy, 1-chloromethyl-2-chloroethoxy, 1-bromomethyl-2-bromoethoxy.

[0055] -C 1～ C4 haloalkoxy groups: those partially or completely substituted with fluorine, chlorine, bromine, and / or iodine as described above. 1～ C4 alkoxy groups, such as fluoromethoxy, difluoromethoxy, trifluoromethoxy, monochlorodifluoromethoxy, monobromodifluoromethoxy, 2-fluoroethoxy, 2-chloroethoxy, 2-bromoethoxy, 2-iodoethoxy, 2,2-difluoroethoxy, 2,2,2-trifluoroethoxy, 2-chloro-2-fluoroethoxy, 2-chloro-2,2-difluoroethoxy, 2,2-dichloro-2-fluoroethoxy, 2,2,2-trichloroethoxy, pentafluoroethoxy, 2-fluoropropoxy, 3-fluoropropoxy, 2-chloro... Propoxy, 3-chloropropoxy, 2-bromopropoxy, 3-bromopropoxy, 2,2-difluoropropoxy, 2,3-difluoropropoxy, 2,3-dichloropropoxy, 3,3,3-trifluoropropoxy, 3,3,3-trichloropropoxy, 2,2,3,3,3-pentafluoropropoxy, heptafluoropropoxy, 1-fluoromethyl-2-fluoroethoxy, 1-chloromethyl-2-chloroethoxy, 1-bromomethyl-2-bromoethoxy, 4-fluorobutoxy, 4-chlorobutoxy, 4-bromobutoxy, and nonafluorobutoxy.

[0056] -C 1～ C6 haloalkoxy group: except for the C as described above 1～ In addition to C4 haloalkoxy groups, there are also, for example, 5-fluoropentoxy, 5-chloropentoxy, 5-bromopentoxy, 5-iodopentoxy, undecylfluoropentoxy, 6-fluorohexyloxy, 6-chlorohexyloxy, 6-bromohexyloxy, 6-iodohexyloxy, and dodecafluorohexyloxy.

[0057] -C 1～ C4 alkylthio groups: such as methylthio, ethylthio, propanethio, 1-methylethylthio, butylthio, 1-methylpropanethio, 2-methylpropanethio, and 1,1-dimethylethylthio.

[0058] -C 1～ C6 alkylthio group: except for -C as described above 1～ Besides C4 alkylthio, there are also pentylthio, 1-methylbutyrothio, 2-methylbutyrothio, 3-methylbutyrothio, 2,2-dimethylpropanethio, 1-ethylpropanethio, hexylthio, 1,1-dimethylpropanethio, 1,2-dimethylpropanethio, 1-methylpentylthio, 2-methylpentylthio, 3-methylpentylthio, 4-methylpentylthio, 1,1-dimethylbutyrothio, 1,2-dimethylbutyrothio, 1,3-dimethylbutyrothio, 2,2-dimethylbutyrothio, 2,3-dimethylbutyrothio, 3,3-dimethylbutyrothio, 1-ethylbutyrothio, 2-ethylbutyrothio, 1,1,2-trimethylpropanethio, 1,2,2-trimethylpropanethio, 1-ethyl-1-methylpropanethio, and 1-ethyl-2-methylpropanethio.

[0059] -C 1～ C6 alkyl sulfinyl groups: such as methyl sulfinyl, ethyl sulfinyl, propyl sulfinyl, 1-methylethyl sulfinyl, butyl sulfinyl, 1-methylpropyl sulfinyl, 2-methylpropyl sulfinyl, 1,1-dimethylethyl sulfinyl, pentyl sulfinyl, 1-methylbutyl sulfinyl, 2-methylbutyl sulfinyl, 3-methylbutyl sulfinyl, 2,2-dimethylpropyl sulfinyl, 1-ethylpropyl sulfinyl, 1,1-dimethylpropyl sulfinyl, 1,2-dimethylpropyl sulfinyl, hexyl sulfinyl, 1-methylpentyl sulfinyl, 2-methyl 1,1-dimethylbutylsulfinyl, 3-methylpentylsulfinyl, 4-methylpentylsulfinyl, 1,2-dimethylbutylsulfinyl, 1,3-dimethylbutylsulfinyl, 2,2-dimethylbutylsulfinyl, 2,3-dimethylbutylsulfinyl, 3,3-dimethylbutylsulfinyl, 1-ethylbutylsulfinyl, 2-ethylbutylsulfinyl, 1,1,2-trimethylpropylsulfinyl, 1,2,2-trimethylpropylsulfinyl, 1-ethyl-1-methylpropylsulfinyl, and 1-ethyl-2-methylpropylsulfinyl.

[0060] -C 1～C6 alkylsulfonyl groups: such as methylsulfonyl, ethylsulfonyl, propylsulfonyl, 1-methylethylsulfonyl, butylsulfonyl, 1-methylpropylsulfonyl, 2-methylpropylsulfonyl, 1,1-dimethylethylsulfonyl, pentylsulfonyl, 1-methylbutylsulfonyl, 2-methylbutylsulfonyl, 3-methylbutylsulfonyl, 1,1-dimethylpropylsulfonyl, 1,2-dimethylpropylsulfonyl, 2,2-dimethylpropylsulfonyl, 1-ethylpropylsulfonyl, hexylsulfonyl, 1-methylpentylsulfonyl, 2-methylpentylsulfonyl 1,1-dimethylbutylsulfonyl, 1,2-dimethylbutylsulfonyl, 1,3-dimethylbutylsulfonyl, 2,2-dimethylbutylsulfonyl, 2,3-dimethylbutylsulfonyl, 3,3-dimethylbutylsulfonyl, 1-ethylbutylsulfonyl, 2-ethylbutylsulfonyl, 1,1,2-trimethylpropylsulfonyl, 1,2,2-trimethylpropylsulfonyl, 1-ethyl-1-methylpropylsulfonyl and 1-ethyl-2-methylpropylsulfonyl.

[0061] -C 1～ C4 alkylamino groups: such as methylamino, ethylamino, propylamino, 1-methylethylamino, butylamino, 1-methylpropylamino, 2-methylpropylamino, or 1,1-dimethylethylamino.

[0062] -C 1～ C6 alkylamine group: except for -C as described above 1～ Besides C4 alkylamino, there are also, for example, pentylamino, butylamino, 2-methylbutylamino, 3-methylbutylamino, 2,2-dimethylpropylamino, 1-ethylpropylamino, hexylamino, 1,1-dimethylpropylamino, 1,2-dimethylpropylamino, 1-methylpentylamino, 2-methylpentylamino, 3-methylpentylamino, 4-methylpentylamino, 1,1-dimethylbutylamino, 1,2-dimethylbutylamino, 1,3-dimethylbutylamino, 2,2-dimethylbutylamino, 2,3-dimethylbutylamino, 3,3-dimethylbutylamino, 1-ethylbutylamino, 2-ethylbutylamino, 1,1,2-trimethylpropylamino, 1,2,2-trimethylpropylamino, 1-ethyl-1-methylpropylamino, and 1-ethyl-2-methylpropylamino.

[0063] -II-C 1～ C4 alkylamine groups: for example, N-methyl-N-methylamine, N-methyl-N-ethylamine, N-methyl-N-propylamine, N-methyl-N-butylamine, N-ethyl-N-ethylamine, N-ethyl-N-propylamine, N-ethyl-N-butylamine, N-propyl-N-propylamine, N-propyl-N-butylamine, N-butyl-N-butylamine.

[0064] -II-C 1～ C6 alkylamine group: except for the di-C group as described above. 1～Besides C4 alkylamine, there are also N-methyl-N-pentylamine, N-methyl-N-(1-methylbutyl)amine, N-methyl-N-(2-methylbutyl)amine, N-methyl-(3-methylbutyl)amine, N-methyl-N-(2,2-dimethylpropyl)amine, N-methyl-N-(1-ethylpropyl)amine, N-methyl-N-hexylamine, N-methyl-N-(1,1-dimethylpropyl)amine, N-methyl-N-(1,2-dimethylpropyl)amine, N-methyl-N-(1-methylpentyl)amine, N-methyl-N-(2-methylpentyl)amine, N-methyl-N-(3-methylpentyl)amine, N-methyl-N- (4-Methylpentyl)amino, N-methyl-N-(1,1-dimethylbutyl)amino, N-methyl-N-(1,2-dimethylbutyl)amino, N-methyl-N-(1,3-dimethylbutyl)amino, N-methyl-N-(2,2-dimethylbutyl)amino, N-methyl-N-(2,3-dimethylbutyl)amino, N-methyl-N-(3,3-dimethylbutyl)amino, N-methyl-N-(1-ethylbutyl)amino, N-methyl-N-(2-ethylbutyl)amino, N-methyl-N-(1,1,2-trimethylpropyl)amino, N-methyl-N-(1,2,2-trimethylpropyl)amino, N-methyl-N-(1-ethylbutyl)amino -1-Methylpropyl)amino, N-methyl-N-(1-ethyl-2-methylpropyl)amino, N-ethyl-N-pentylamino, N-ethyl-N-(1-methylbutyl)amino, N-ethyl-N-(2-methylbutyl)amino, N-ethyl-N-(3-methylbutyl)amino, N-ethyl-N-(2,2-dimethylpropyl)amino, N-ethyl-N-(1-ethylpropyl)amino, N-ethyl-N-hexylamino, N-ethyl-N-(1,1-dimethylpropyl)amino, N-ethyl-N-(1,2-dimethylpropyl)amino, N-ethyl-N-(1-methylpentyl)amino, N-ethyl-N-(2-methylpentyl)amino, N -Ethyl-N-(3-methylpentyl)amino, N-ethyl-N-(4-methylpentyl)amino, N-ethyl-N(1,1-dimethylbutyl)amino, N-ethyl-N-(1,2-dimethylbutyl)amino, N-ethyl-N-(1,3-dimethylbutyl)amino, N-ethyl-N-(2,2-dimethylbutyl)amino, N-ethyl-N-(2,3-dimethylbutyl)amino, N-ethyl-N-(3,3-dimethylbutyl)amino, N-ethyl-N-(1-ethylbutyl)amino, N-ethyl-N-(2-ethylbutyl)amino, N-ethyl-N-(1,1,2-trimethylpropyl)amino, N-ethyl-N-(1,2,2-Trimethylpropyl)amino, N-ethyl-N-(1-ethyl-1-methylpropyl)amino, N-ethyl-N-(1-ethyl-2-methylpropyl)amino, N-propyl-N-pentylamino, N-butyl-N-pentylamino, N,N-dipentylamino, N-propyl-N-hexylamino, N-butyl-N-hexylamino, N-pentyl-N-hexylamino, or N,N-dihexylamino.

[0065] -C 3～ C6 alkenyl groups: such as 1-propenyl, 2-propenyl, 1-methylvinyl, 1-butenyl, 2-butenyl, 3-butenyl, 1-methyl-1-propenyl, 2-methyl-1-propenyl, 1-methyl-2-propenyl, 2-methyl-2-propenyl, 1-pentenyl, 2-pentenyl, 3-pentenyl, 4-pentenyl, 1-methyl-1-butenyl, 2-methyl-1-butenyl, 3-methyl-1-butenyl, 1-methyl-2-butenyl, 2-methyl-2-butenyl, 3-methyl-2-butenyl, 1-methyl-3-butenyl, 2-methyl-3-butenyl. 3-Methyl-3-butenyl, 1,1-dimethyl-2-propenyl, 1,2-dimethyl-1-propenyl, 1,2-dimethyl-2-propenyl, 1-ethyl-1-propenyl, 1-ethyl-2-propenyl, 1-hexenyl, 2-hexenyl, 3-hexenyl, 4-hexenyl, 5-hexenyl, 1-methyl-1-pentenyl, 2-methyl-1-pentenyl, 3-methyl-1-pentenyl, 4-methyl-1-pentenyl, 1-methyl-2-pentenyl, 2-methyl-2-pentenyl, 3-methyl-2-pentenyl, 4-methyl-2-pentenyl, 1-methyl-3-pentenyl 2-Methyl-3-pentenyl, 3-Methyl-3-pentenyl, 4-Methyl-3-pentenyl, 1-Methyl-4-pentenyl, 2-Methyl-4-pentenyl, 3-Methyl-4-pentenyl, 4-Methyl-4-pentenyl, 1,1-dimethyl-2-butenyl, 1,1-dimethyl-3-butenyl, 1,2-dimethyl-1-butenyl, 1,2-dimethyl-2-butenyl, 1,2-dimethyl-3-butenyl, 1,3-dimethyl-1-butenyl, 1,3-dimethyl-2-butenyl, 1,3-dimethyl-3-butenyl, 2,2-dimethyl-3-butenyl alkenyl, 2,3-dimethyl-1-butenyl, 2,3-dimethyl-2-butenyl, 2,3-dimethyl-3-butenyl, 3,3-dimethyl-1-butenyl, 3,3-dimethyl-2-butenyl, 1-ethyl-1-butenyl, 1-ethyl-2-butenyl, 1-ethyl-3-butenyl, 2-ethyl-1-butenyl, 2-ethyl-2-butenyl, 2-ethyl-3-butenyl, 1,1,2-trimethyl-2-propenyl, 1- and 1-methyl-2-propenyl, 1-ethyl-2-methyl-1-propenyl and 1-ethyl-2-methyl-2-propenyl.

[0066] -C 3～ C6 haloalkenyl groups: those partially or completely substituted with fluorine, chlorine, bromine, and / or iodine as described above. 3～ C6 alkenyl groups, such as 2-chloroprop-2-en-1-yl, 3-chloroprop-2-en-1-yl, 2,3-dichloroprop-2-en-1-yl, 3,3-dichloroprop-2-en-1-yl, 2,2,3-trichloroprop-2-en-1-yl, 2,3-dichlorobut-2-en-1-yl, 2-bromoprop-2-en-1-yl, 3-bromoprop-2-en-1-yl, 2,3-dibromoprop-2-en-1-yl, 3,3-dibromoprop-2-en-1-yl, 2,3,3-tribromoprop-2-en-1-yl, or 2,3-dibromobut-2-en-1-yl.

[0067] -C 3～ C6 ynyl groups: such as 1-propynyl, 2-propynyl, 1-butynyl, 2-butynyl, 3-butynyl, 1-methyl-2-propynyl, 2-pentynyl, 3-pentynyl, 4-pentynyl, 1-methyl-2-butynyl, 1-methyl-3-butynyl, 2-methyl-3-butynyl, 3-methyl-1-butynyl, 1,1-dimethyl-2-propynyl, 1-ethyl-2-propynyl, 1-hexynyl, 2-hexynyl, 3-hexynyl, 4-hexynyl, 5-hexynyl, 1-methyl-2-pentynyl, 1-methyl-3-pentynyl, 1-methyl- 4-Pentynyl, 2-Methyl-3-pentynyl, 2-Methyl-4-pentynyl, 3-Methyl-1-pentynyl, 3-Methyl-4-pentynyl, 4-Methyl-1-pentynyl, 4-Methyl-2-pentynyl, 1,1-Dimethyl-2-butynyl, 1,1-Dimethyl-3-butynyl, 1,2-Dimethyl-3-butynyl, 2,2-Dimethyl-3-butynyl, 3,3-Dimethyl-1-butynyl, 1-Ethyl-2-butynyl, 1-Ethyl-3-butynyl, 2-Ethyl-3-butynyl and 1-Ethyl-1-methyl-2-propynyl.

[0068] -C 3～ C6 halogenated alkynyl group: The C group as described above is partially or completely substituted with fluorine, chlorine, bromine, and / or iodine. 3～ C6 ynyl groups, such as 1,1-fluoroprop-2-yn-1-yl, 3-chloroprop-2-yn-1-yl, 3-bromoprop-2-yn-1-yl, 3-iodoprop-2-yn-1-yl, 4-fluorobut-2-yn-1-yl, 4-chlorobut-2-yn-1-yl, 1,1-difluorobut-2-yn-1-yl, 4-iodobut-3-yn-1-yl, 5-fluoropent-3-yn-1-yl, 5-iodopent-4-yn-1-yl, 6-fluorohex-4-yn-1-yl, or 6-iodohex-5-yn-1-yl.

[0069] -C 3～C6 cycloalkyl: Monocyclic saturated hydrocarbons with 3 to 6 ring members, such as cyclopropyl, cyclobutyl, cyclopentyl, and cyclohexyl.

[0070] Five- to six-membered heterocycles, including saturated heterocycles and aromatic heterocycles, such as five-membered saturated heterocycles: 2-tetrahydrofuranyl, 3-tetrahydrofuranyl, 2-tetrahydrothiophenyl, 3-tetrahydrothiophenyl, 1-pyrrolidinyl, 2-pyrrolidinyl, 3-pyrrolidinyl, 3-isooxazolyl, 4-isooxazolyl, 5-isooxazolyl, 2-isothiazolyl, 3-isothiazolyl, 4-isothiazolyl, 5-isothiazolyl, 1-pyrazolyl, 3-pyrazolyl, 5-pyrazolyl, 2-oxazolyl, 4-oxazolyl, 5-oxazolyl, 2-thiazolyl, 4-thiazolyl. Alkyl, 5-thiazolyl, 1-imidazolyl, 2-imidazolyl, 4-imidazolyl, 3-oxazolyl, 1,2,4-oxadiazolyl-3-yl, 1,2,4-oxadiazolyl-5-yl, 3-thiazolyl, 1,2,4-thiadiazolyl-3-yl, 1,2,4-thiadiazolyl-5-yl, 1,2,4-triazolyl-3-yl, 1,2,4-oxadiazolyl-2-yl, 1,2,4-oxadiazolyl-4-yl, 1,3,4-oxadiazolyl-2-yl, 1,2,4-thiadiazolyl-2-yl, 1,2,4-thiadiazolyl-4 -yl, 1,3,4-thiadiazol-2-yl, 1,2,4-triazol-1-yl, 1,3,4-triazol-2-yl; 6-membered saturated heterocycles: 1-piperidinyl, 2-piperidinyl, 3-piperidinyl, 4-piperidinyl, 1,3-dioxane-5-yl, 1,4-dioxane, 1,3-dithiaane-5-yl, 1,3-dithiaane, 1,3-oxothiacyclohexane-5-yl, 1,4-oxothiacyclohexane, 2-tetrahydropyranyl, 3-tetrahydropyranyl, 4-tetrahydropyranyl, 2-tetrahydrothiaranyl, 3-tetrahydrothiaranyl, 4-tetrahydrothiaranyl 1-Hexazinyl, 3-Hexazinyl, 4-Hexazinyl, 1-Hexazinyl, 2-Hexazinyl, 4-Hexazinyl, 5-Hexazinyl, 1-piperazinyl, 2-piperazinyl, 1,3,5-Hexhydrotriazin-1-yl, 1,3,5-Hexhydrotriazin-2-yl, 1,2,4-Hexhydrotriazin-1-yl, 1,2,4-Hexhydrotriazin-3-yl, tetrahydro-1,3-oxazin-1-yl, tetrahydro-1,3-oxazin-2-yl, tetrahydro-1,3-oxazin-6-yl, 1-morpholinyl, 2-morpholinyl, 3-morpholinyl;Five-membered unsaturated heterocycles: furanyl (e.g., 2-furanyl, 3-furanyl), thiopheneyl (e.g., 2-thiopheneyl, 3-thiopheneyl), pyrroloyl (e.g., pyrrolo-2-yl, pyrrolo-3-yl), pyrazolyl (e.g., pyrazol-3-yl, pyrazol-4-yl), isoxazolyl (e.g., isoxazol-3-yl, isoxazol-4-yl, isoxazol-5-yl), isothiazolyl (e.g., isothiazol-3-yl, isothiazol-4-yl, isothiazol-5-yl). (e.g., imidazole-5-yl), imidazole (e.g., imidazole-2-yl, imidazole-4-yl), oxazolyl (e.g., oxazol-2-yl, oxazol-4-yl, oxazol-5-yl), thiazolyl (e.g., thiazolyl-2-yl, thiazolyl-4-yl, thiazolyl-5-yl), oxadiazolyl (e.g., 1,2,3-oxadiazol-4-yl, 1,2,3-oxadiazol-5-yl, 1,2,4-oxadiazol-3-yl, 1,2,4-oxadiazol-5-yl) -yl, 1,3,4-oxadiazol-2-yl), thiadiazolyl (e.g., 1,2,3-thiadiazol-4-yl, 1,2,3-thiadiazol-5-yl, 1,2,4-thiadiazol-3-yl, 1,2,4-thiadiazol-5-yl, 1,3,4-thiadiazol-2-yl), triazolyl (e.g., 1,2,3-triazol-4-yl, 1,2,4-triazol-3-yl), 1-tetraazolyl; 6-membered unsaturated hetero Ring: pyridinyl (e.g., pyridin-2-yl, pyridin-3-yl, pyridin-4-yl), pyridazinyl (e.g., pyridazin-3-yl, pyridazin-4-yl), pyrimidinyl (e.g., pyrimidin-2-yl, pyrimidin-4-yl, pyrimidin-5-yl), pyrazin-2-yl, triazinyl (e.g., 1,3,5-triazin-2-yl, 1,2,4-triazin-3-yl, 1,2,4-triazin-5-yl, 1,2,4-triazin-6-yl).

[0071] Based on the definitions and descriptions of the substituents mentioned above, this invention provides some preferred and representative 3,6-disubstituted benzothiazole compounds.

[0072] By way of example, 3,6-disubstituted benzothiazole compounds of formula (IAa) are preferred, wherein the substituent R 1 For CF3, substituent R 2 Cl, substituent R 3 It is CH3. Specifically, the substituent R... 4 With a preferred meaning, the present invention specifically lists R as shown in Table 1. 4 Substituent groups. Thus, the general formula (IAa) represents a specific, most preferred class of 3,6-disubstituted benzothiazole compounds represented by IAa01 to IAa166.

[0073]

[0074]

[0075] Table 1. Representative R values ​​of compounds represented by general formula IAa4 Substituents

[0076]

[0077]

[0078]

[0079]

[0080] By way of example, 3,6-disubstituted benzothiazole compounds of formula (IAb) are preferred, wherein the substituent R 1 For CF3, substituent R 2 Cl, substituent R 3 It is C2H5. Specifically, in the general formula (IAb), the substituent R... 4 The structures are shown in Table 1, with groups numbered 01 to 166. Thus, the general formula (IAb) represents a specific, most preferred class of 3,6-disubstituted benzothiazole compounds represented by IAb01 to IAb166.

[0081]

[0082] By way of example, 3,6-disubstituted benzothiazole compounds of formula (IAc) are preferred, wherein the substituent R 1 For CF3, substituent R 2 Cl, substituent R 3 It is n-propyl. Specifically, in the general formula (IAc), the substituent R... 4 The structures are shown in Table 1, with groups numbered 01 to 166. Thus, the general formula (IAc) represents a specific, most preferred class of 3,6-disubstituted benzothiazole compounds represented by IAc01 to IAc166.

[0083]

[0084] By way of example, 3,6-disubstituted benzothiazole compounds of formula (IAd) are preferred, wherein the substituent R 1 For CF3, substituent R 2 Cl, substituent R 3 It is n-butyl. Specifically, in the general formula (IAd), the substituent R... 4 The structures are shown in Table 1, with groups numbered 01 to 166. Thus, the general formula (IAd) represents a specific, most preferred class of 3,6-disubstituted benzothiazole compounds represented by IAd01 to IAd166.

[0085]

[0086] By way of example, 3,6-disubstituted benzothiazole compounds of formula (IAe) are preferred, wherein the substituent R 1 For CF3, substituent R 2 Cl, substituent R 3 It is n-pentyl. Specifically, in the general formula (IAe), the substituent R... 4 The structures are shown in Table 1, with groups numbered 01 to 166. Thus, the general formula (IAe) represents a specific, most preferred class of 3,6-disubstituted benzothiazole compounds represented by IAe01 to IAe166.

[0087]

[0088] By way of example, 3,6-disubstituted benzothiazole compounds of formula (IAf) are preferred, wherein the substituent R 1 For CF3, substituent R 2 Cl, substituent R 3 It is an orthohexyl group. Specifically, in the general formula (IAf), the substituent R... 4 The structures are shown in Table 1, with groups numbered 01 to 166. Thus, the general formula (IAf) represents a specific, most preferred class of 3,6-disubstituted benzothiazole compounds represented by IAf01 to IAf166.

[0089]

[0090] By way of example, 3,6-disubstituted benzothiazole compounds of formula (IAg) are preferred, wherein the substituent R 1 For CF3, substituent R 2 Cl, substituent R 3 It is n-heptyl. Specifically, in the general formula (IAg), the substituent R... 4 The structures are shown in Table 1, with groups numbered 01 to 166. Thus, the general formula (IAg) represents a specific, most preferred class of 3,6-disubstituted benzothiazole compounds represented by IAG01 to IAG166.

[0091]

[0092] By way of example, 3,6-disubstituted benzothiazole compounds of formula (IBa) are preferred, wherein the substituent R 1 For CF3, substituent R 2 For F, substituent R 3 It is CH3. Specifically, the substituent R... 4 With a preferred meaning, the present invention specifically lists R as shown in Table 1. 4Substituent groups. Thus, the general formula (IBa) represents a specific, most preferred class of 3,6-disubstituted benzothiazole compounds represented by IBa01 to IBa166.

[0093]

[0094] By way of example, 3,6-disubstituted benzothiazole compounds of formula (IBb) are preferred, wherein the substituent R 1 For CF3, substituent R 2 For F, substituent R 3 It is C2H5. Specifically, the substituent R in the general formula (IBb) 4 The structures are shown in Table 1, with groups numbered 01 to 166. Thus, the general formula (IBb) represents a specific, most preferred class of 3,6-disubstituted benzothiazole compounds represented by IBb01 to IBb166.

[0095]

[0096] By way of example, 3,6-disubstituted benzothiazole compounds of formula (IBc) are preferred, wherein the substituent R 1 For CF3, substituent R 2 For F, substituent R 3 It is n-propyl. Specifically, in the general formula (IBc), the substituent R... 4 The structures are shown in Table 1, with groups numbered 01 to 166. Thus, the general formula (IBc) represents a specific, most preferred class of 3,6-disubstituted benzothiazole compounds represented by IBc01 to IBc166.

[0097]

[0098] By way of example, 3,6-disubstituted benzothiazole compounds of formula (IBd) are preferred, wherein the substituent R 1 For CF3, substituent R 2 For F, substituent R 3 It is n-butyl. Specifically, in the general formula (IBd), the substituent R... 4 The structures are shown in Table 1, with groups numbered 01 to 166. Thus, the general formula (IBd) represents a specific, most preferred class of 3,6-disubstituted benzothiazole compounds represented by IBd01 to IBd166.

[0099]

[0100] By way of example, 3,6-disubstituted benzothiazole compounds of formula (IBe) are preferred, wherein the substituent R 1 For CF3, substituent R 2For F, substituent R 3 It is n-pentyl. Specifically, in the general formula (IBe), the substituent R... 4 The structures are shown in Table 1, with groups numbered 01 to 166. Thus, the general formula (IBe) represents a specific, most preferred class of 3,6-disubstituted benzothiazole compounds represented by IBe01 to IBe166.

[0101]

[0102] By way of example, 3,6-disubstituted benzothiazole compounds of formula (IBf) are preferred, wherein the substituent R 1 For CF3, substituent R 2 For F, substituent R 3 For hexyl group. Specifically, in the general formula (IBf), the substituent R... 4 The structures are shown in Table 1, with groups numbered 01 to 166. Thus, the general formula (IBf) represents a specific, most preferred class of 3,6-disubstituted benzothiazole compounds represented by IBf01 to IBf166.

[0103]

[0104] By way of example, 3,6-disubstituted benzothiazole compounds of formula (IBg) are preferred, wherein the substituent R 1 For CF3, substituent R 2 For F, substituent R 3 It is n-heptyl. Specifically, in the general formula (IBg), the substituent R... 4 The structures are shown in Table 1, with groups numbered 01 to 166. Thus, the general formula (IBg) represents a specific, most preferred class of 3,6-disubstituted benzothiazole compounds represented by IBg01 to IBg166.

[0105]

[0106] By way of example, 3,6-disubstituted benzothiazole compounds of formula (ICa) are preferred, wherein the substituent R 1 For CF3, substituent R 2 H, substituent R 3 It is CH3. Specifically, the substituent R... 4 With a preferred meaning, the present invention specifically lists R as shown in Table 1. 4 Substituent groups. Thus, the general formula (ICa) represents a specific, most preferred class of 3,6-disubstituted benzothiazole compounds represented by ICa01 to ICa166.

[0107]

[0108] By way of example, 3,6-disubstituted benzothiazole compounds of formula (ICb) are preferred, wherein the substituent R 1 For CF3, substituent R 2 H, substituent R 3 It is C2H5. Specifically, in the general formula (ICb), the substituent R... 4 The structures are shown in Table 1, with groups numbered 01 to 166. Thus, the general formula (ICb) represents a specific, most preferred class of 3,6-disubstituted benzothiazole compounds represented by ICb01 to ICb166.

[0109]

[0110] By way of example, 3,6-disubstituted benzothiazole compounds of formula (ICc) are preferred, wherein the substituent R 1 For CF3, substituent R 2 H, substituent R 3 It is n-propyl. Specifically, in the general formula (ICc), the substituent R... 4 The structures are shown in Table 1, with groups numbered 01 to 166. Thus, the general formula (ICc) represents a specific, most preferred class of 3,6-disubstituted benzothiazole compounds represented by ICc01 to ICc166.

[0111]

[0112] By way of example, 3,6-disubstituted benzothiazole compounds of formula (ICd) are preferred, wherein the substituent R 1 For CF3, substituent R 2 H, substituent R 3 It is n-butyl. Specifically, in the general formula (ICd), the substituent R... 4 The structures are shown in Table 1, with groups numbered 01 to 166. Thus, the general formula (ICd) represents a specific, most preferred class of 3,6-disubstituted benzothiazole compounds represented by ICd01 to ICd166.

[0113]

[0114] By way of example, 3,6-disubstituted benzothiazole compounds of formula (ICe) are preferred, wherein the substituent R 1 For CF3, substituent R 2 H, substituent R 3 It is n-pentyl. Specifically, in the general formula (ICe), the substituent R... 4The structures are shown in Table 1, with groups numbered 01 to 166. Thus, the general formula (ICe) represents a specific, most preferred class of 3,6-disubstituted benzothiazole compounds represented by ICe01 to ICe166.

[0115]

[0116] By way of example, 3,6-disubstituted benzothiazole compounds of formula (ICf) are preferred, wherein the substituent R 1 For CF3, substituent R 2 H, substituent R 3 For hexyl group. Specifically, in the general formula (ICf), the substituent R... 4 The structures are shown in Table 1, with groups numbered 01 to 166. Thus, the general formula (ICf) represents a specific, most preferred class of 3,6-disubstituted benzothiazole compounds represented by ICf01 to ICf166.

[0117]

[0118] By way of example, 3,6-disubstituted benzothiazole compounds of formula (ICg) are preferred, wherein the substituent R 1 For CF3, substituent R 2 H, substituent R 3 It is n-heptyl. Specifically, in the general formula (ICg), the substituent R... 4 The structures are shown in Table 1, with groups numbered 01 to 166. Thus, the general formula (ICg) represents a specific, most preferred class of 3,6-disubstituted benzothiazole compounds represented by ICg01 to ICg166.

[0119]

[0120] This invention provides, by way of example, some 3,6-disubstituted benzothiazole compounds: IAa01~IAa166, IAb01~IAb166, IAc01~IAc166, IAd01~IAd166, IAe01~IAe166, IAF01~IAf166, IAG01~IAg166, IBa01~IBa166, IBb01~IBb166, IBc01~ The following are listed 3,6-disubstituted benzothiazole compounds, with particular emphasis on the substituent R.3 C 1～ C8 (linear) alkyl group, substituent R 4 It can be any of the groups shown in Table 1. Those skilled in the art, based on the technical teachings of this invention, can modify the substituent R... 1 ~R 4 By substituting the functional groups, more novel 3,6-disubstituted benzothiazole compounds can be designed.

[0121] This invention further provides a chemical synthesis method for 3,6-disubstituted benzothiazole compounds. Preferably, the preparation route for 3,6-disubstituted benzothiazole compounds is shown in Scheme 1. It should be noted that the parameters and conditions shown in Scheme 1 are merely illustrative and should not be construed as limiting the selection of parameters and conditions for the preparation route of this invention to illustrative purposes. Furthermore, the meanings of substituents in the reactants, intermediates, target products, etc., involved in the preparation route Scheme 1 remain consistent with those described above in this invention.

[0122] Scheme 1:

[0123]

[0124] The 3,6-disubstituted benzothiazole compound (target product) represented by general formula I-01 is prepared by reacting 3-pyridyl-6-hydroxybenzothiazole one (II) with intermediate III-01. In intermediate general formula III-01, the substituent X is a leaving group, which is usually a halogen (such as fluorine, chlorine, bromine or iodine), p-toluenesulfonyl, or methanesulfonyl.

[0125]

[0126] In the reaction to prepare the target product I-01, the reaction temperature is set in the range of room temperature (e.g., 20°C to 30°C) to the boiling point of the reaction mixture, preferably 60°C to 180°C, and particularly preferably 80°C to 150°C. This reaction also needs to be carried out in a suitable solvent and in the presence of a base.

[0127] In this preparation route, a suitable solvent is one capable of at least partially, and preferably completely, dissolving reactants II and III-01 under the reaction conditions. For example, suitable solvents may be selected from aromatic solvents such as benzene, chlorobenzene, toluene, o-xylene, m-xylene, and p-xylene; nitrile solvents such as acetonitrile and propionitrile; ketones such as acetone, methyl ethyl ketone, diethyl ketone, and tert-butyl methyl ketone; halogenated hydrocarbon solvents such as dichloromethane and 1,2-dichloroethane; and N,N-dimethylformamide (DMF), dimethyl sulfoxide (DMSO), and dioxane. Those skilled in the art may also use mixtures of the aforementioned solvents.

[0128] In this preparation route, the base used is preferably an inorganic base, such as alkali metal and alkaline earth metal oxides such as lithium oxide, sodium oxide, calcium oxide, and magnesium oxide; alkali metal and alkaline earth metal hydrides such as lithium hydride, sodium hydride, potassium hydride, and calcium hydride; alkali metal and alkaline earth metal carbonates such as lithium carbonate, potassium carbonate, sodium carbonate, calcium carbonate, and cesium carbonate; alkali metal bicarbonates such as sodium bicarbonate; organic acid salts of alkali metals such as potassium acetate and sodium acetate; lower alkali metal alkoxides such as potassium tert-butoxide, sodium tert-butoxide, sodium ethoxide, and sodium methoxide; and sodium hydroxide or potassium hydroxide. In some embodiments, the base used can also be an organic base, such as trimethylamine, triethylamine, N,N-diisopropylethylamine, N-methylpiperidine, pyridine, N-methylmorpholine, and 4-dimethylaminopyridine.

[0129] The 3,6-disubstituted benzothiazole compound (target product) represented by general formula I-02 is prepared by reacting 3-pyridyl-6-hydroxybenzothiazole one (II) with intermediate III-02. The substituent X in intermediate general formula III-02 is a leaving group, typically a halogen (such as fluorine, chlorine, bromine, or iodine), p-toluenesulfonyl, or methanesulfonyl.

[0130] The reaction conditions are similar to those for the synthesis of 3,6-disubstituted benzothiazole compounds represented by general formula I-01.

[0131]

[0132] The 3,6-disubstituted benzothiazole compound (target product) represented by general formula I-03 is prepared by reacting 3-pyridyl-6-hydroxybenzothiazole one (II) with intermediate III-03. In intermediate general formula III-03, the substituent X is a leaving group, typically a halogen (such as fluorine, chlorine, bromine, or iodine), p-toluenesulfonyl, or methanesulfonyl.

[0133] The reaction conditions are similar to those for the synthesis of 3,6-disubstituted benzothiazole compounds represented by general formula I-01.

[0134]

[0135] The 3,6-disubstituted benzothiazole compound (target product) shown in general formula I-04 is prepared by reacting 3-pyridyl-6-hydroxybenzothiazole one (II) with intermediate III-04. In intermediate general formula III-04, the substituent X is a leaving group, usually a halogen (such as fluorine, chlorine, bromine or iodine), p-toluenesulfonyl, or methanesulfonyl.

[0136] The reaction conditions are similar to those for the synthesis of 3,6-disubstituted benzothiazole compounds represented by general formula I-01.

[0137]

[0138] The 3,6-disubstituted benzothiazole compound (target product) shown in general formula I-05 is prepared by reacting 3-pyridyl-6-hydroxybenzothiazole one (II) with intermediate III-05. In intermediate general formula III-05, the substituent X is a leaving group, which is usually a halogen (such as fluorine, chlorine, bromine or iodine), p-toluenesulfonyl, or methanesulfonyl.

[0139] The reaction conditions are similar to those for the synthesis of 3,6-disubstituted benzothiazole compounds represented by general formula I-01.

[0140]

[0141] The 3,6-disubstituted benzothiazole compound (target product) represented by general formula I-06 is prepared by reacting 3-pyridyl-6-hydroxybenzothiazole one (II) with intermediate III-06. In intermediate III-06, the substituent X is a leaving group, typically a halogen (such as fluorine, chlorine, bromine, or iodine), p-toluenesulfonyl, or methanesulfonyl.

[0142] The reaction conditions are similar to those for the synthesis of 3,6-disubstituted benzothiazole compounds represented by general formula I-01.

[0143]

[0144] The 3,6-disubstituted benzothiazole compound (target product) represented by general formula I-07 is prepared by reacting 3-pyridyl-6-hydroxybenzothiazole one (II) with intermediate III-07. In intermediate III-07, the substituent X is a leaving group, typically a halogen (such as fluorine, chlorine, bromine, or iodine), p-toluenesulfonyl, or methanesulfonyl.

[0145] The reaction conditions are similar to those for the synthesis of 3,6-disubstituted benzothiazole compounds represented by general formula I-01.

[0146]

[0147] The 3,6-disubstituted benzothiazole compound (target product) represented by general formula I-08 is prepared by reacting 3-pyridyl-6-hydroxybenzothiazole one (II) with intermediate III-08. In intermediate general formula III-08, the substituent X is a leaving group, which is usually a halogen (such as fluorine, chlorine, bromine or iodine), p-toluenesulfonyl, or methanesulfonyl.

[0148] The reaction conditions are similar to those for the synthesis of 3,6-disubstituted benzothiazole compounds represented by general formula I-01.

[0149]

[0150] The 3,6-disubstituted benzothiazole compound (target product) represented by general formula I-09 is prepared by reacting 3-pyridyl-6-hydroxybenzothiazole one (II) with intermediate III-09. In intermediate general formula III-09, the substituent X is a leaving group, which is usually a halogen (such as fluorine, chlorine, bromine or iodine), p-toluenesulfonyl, or methanesulfonyl.

[0151] The reaction conditions are similar to those for the synthesis of 3,6-disubstituted benzothiazole compounds represented by general formula I-01.

[0152]

[0153] The 3,6-disubstituted benzothiazole compound (target product) represented by general formula I-10 is prepared by reacting 3-pyridyl-6-hydroxybenzothiazole one (II) with intermediate III-10. In intermediate general formula III-10, the substituent X is a leaving group, which is usually a halogen (such as fluorine, chlorine, bromine or iodine), p-toluenesulfonyl, or methanesulfonyl.

[0154] The reaction conditions are similar to those for the synthesis of 3,6-disubstituted benzothiazole compounds represented by general formula I-01.

[0155]

[0156] The 3,6-disubstituted benzothiazole compound (target product) represented by general formula I-11 is prepared by reacting 3-pyridyl-6-hydroxybenzothiazole one (II) with intermediate III-11. In intermediate general formula III-11, the substituent X is a leaving group, which is usually a halogen (such as fluorine, chlorine, bromine or iodine), p-toluenesulfonyl, or methanesulfonyl.

[0157] The reaction conditions are similar to those for the synthesis of 3,6-disubstituted benzothiazole compounds represented by general formula I-01.

[0158]

[0159] This invention further provides a method for synthesizing 3-pyridyl-6-hydroxybenzothiazolone (II). It involves removing the 6-methyl group from 3-pyridyl-6-methoxybenzothiazolone (IV) in an acidic system to obtain compound II. In this synthetic method, the preferred acidic system is HBr / water, BBr3 / dichloromethane, AlCl3 / toluene, etc.

[0160] The reaction temperature for synthesizing compound II is typically room temperature to 160°C. The reaction time is typically 1 to 24 hours.

[0161]

[0162] Preferably, 3-pyridyl-6-methoxybenzothiazole (IV) can be prepared by reacting a 2-halopyridine derivative (VI) with 6-methoxybenzothiazole-2(3H)one (V). The substituent X of the intermediate 2-halopyridine derivative (VI) is a leaving group, typically a halogen (such as fluorine, chlorine, bromine, or iodine), p-toluenesulfonyl, or methanesulfonyl. The reaction temperature is typically set at 60–180°C, preferably 80–150°C. The reaction time is typically 1–24 h. This reaction also needs to be carried out in a suitable solvent and in the presence of a base.

[0163] In this preparation route, a suitable solvent is one that can at least partially, preferably completely, dissolve reactants VI and V under the reaction conditions. For example, suitable solvents may be selected from aromatic solvents such as benzene, chlorobenzene, toluene, o-xylene, m-xylene, and p-xylene; nitrile solvents such as acetonitrile and propionitrile; ketones such as acetone, methyl ethyl ketone, diethyl ketone, and tert-butyl methyl ketone; halogenated hydrocarbon solvents such as dichloromethane and 1,2-dichloroethane; and N,N-dimethylformamide (DMF), dimethyl sulfoxide (DMSO), and dioxane. Those skilled in the art may also use mixtures of the aforementioned solvents.

[0164] In this preparation route, the base used is preferably an inorganic base, such as alkali metal and alkaline earth metal oxides such as lithium oxide, sodium oxide, calcium oxide, and magnesium oxide; alkali metal and alkaline earth metal hydrides such as lithium hydride, sodium hydride, potassium hydride, and calcium hydride; alkali metal and alkaline earth metal carbonates such as lithium carbonate, potassium carbonate, sodium carbonate, calcium carbonate, and cesium carbonate; alkali metal bicarbonates such as sodium bicarbonate; organic acid salts of alkali metals such as potassium acetate and sodium acetate; lower alkali metal alkoxides such as potassium tert-butoxide, sodium tert-butoxide, sodium ethoxide, and sodium methoxide; and sodium hydroxide or potassium hydroxide. In some embodiments, the base used can also be an organic base, such as trimethylamine, triethylamine, N,N-diisopropylethylamine, N-methylpiperidine, pyridine, N-methylmorpholine, and 4-dimethylaminopyridine.

[0165]

[0166] Preferably, the intermediate product 6-methoxybenzothiazolone (V) can be obtained by diazotization of 2-amino-6-methoxybenzothiazolone (VIII) to generate 2-chloro-6-methoxybenzothiazolone (VII). The product (VII) can be obtained by directly acid hydrolyzing VII without separation to obtain V.

[0167]

[0168] The starting reactant in Scheme 1, 2-amino-6-methoxybenzothiazole (VIII), is a commercially available product that can be obtained in large quantities through commercial means.

[0169] As mentioned above, 3,6-disubstituted benzothiazole compounds exist as isomers or optically active derivatives. In particular, when R... 3 When it is not hydrogen, R 3 and R 4 The attached carbon atom is a chiral carbon, and the 3,6-disubstituted benzothiazole compounds shown in Formula I have two optical isomers, R- and S-. This invention further provides a chemical synthesis method for the optical isomers of 3,6-disubstituted benzothiazole compounds, the preparation route of which is shown in Scheme 2.

[0170] Scheme 2:

[0171]

[0172] It should be noted that Scheme 2 uses the R-isomer (RI-01) as an example to illustrate the preparation method of the optically pure R-isomer. The parameters and conditions shown in Scheme 2 are merely illustrative and should not be construed as limiting the selection of parameters and conditions for the preparation route of this invention to illustrative purposes only. Furthermore, the meanings of substituents in the reactants, intermediates, target products, etc., involved in the preparation route Scheme 2 remain consistent in this invention.

[0173] 3-Pyridyl-6-hydroxybenzothiazolinone (II) reacts with the corresponding (S)-(-)-α-substituted product (S-III-01) via an SN2 substitution mechanism, resulting in configuration inversion of the chiral substrate to the R-configuration product (RI-01). The X substituent in intermediate S-III-01 is a halogen, p-toluenesulfonyl, or methanesulfonyl. The reaction temperature is typically set at 60–180 °C, preferably 80–150 °C. The reaction time is typically 1–24 h. This reaction must be carried out in a suitable solvent and in the presence of a base.

[0174] This reaction is preferably carried out in an organic solvent in the presence of an inorganic base. Commonly used organic solvents are preferably aliphatic hydrocarbon solvents such as pentane, hexane, cyclohexane, and C1844. 5～8 Mixtures of alkanes; nitrile solvents such as acetonitrile and propionitrile; aromatic solvents such as toluene, o-xylene, m-xylene, p-xylene, chlorobenzene, etc.; and N,N-dimethylformamide (DMF), dimethyl sulfoxide (DMSO) and dioxane. This reaction can also use mixtures of the aforementioned organic solvents.

[0175] Suitable bases for this reaction are selected from inorganic bases. These include alkali metal and alkaline earth metal oxides such as lithium oxide, sodium oxide, calcium oxide, and magnesium oxide; alkali metal and alkaline earth metal hydrides such as lithium hydride, sodium hydride, potassium hydride, and calcium hydride; alkali metal and alkaline earth metal carbonates such as lithium carbonate, potassium carbonate, sodium carbonate, calcium carbonate, and cesium carbonate; alkali metal bicarbonates such as sodium bicarbonate; organic acid salts of alkali metals such as potassium acetate and sodium acetate; lower alkali metal alkoxides such as potassium tert-butoxide, sodium tert-butoxide, sodium ethoxide, and sodium methoxide; and sodium hydroxide or potassium hydroxide.

[0176] The inventors of this patent investigated the agronomic biological activity of 3,6-disubstituted benzothiazole compounds. Experiments showed that 3,6-disubstituted benzothiazole compounds possess excellent herbicidal activity. At application rates of 0.01–1000 g / ha, preferably 1–500 g / ha, obvious symptoms were observed within hours of treatment with the 3,6-disubstituted benzothiazole compounds described in formula (I), and the weeds died within 1–3 days. Research also found that the 2,6-disubstituted benzothiazole compounds described in formula (I) exhibit extremely high herbicidal activity against various broadleaf weeds and some grassy weeds, and can be used to control weeds resistant to existing herbicides, especially those resistant to ALS inhibitors, PSII inhibitors, ACCase inhibitors, and EPSP inhibitors.

[0177] In particular, the inventors of this patent also investigated the differences in herbicidal activity among different isomers of 3,6-disubstituted benzothiazole compounds. The study found that the R-isomer exhibited superior activity compared to the S-isomer. This means that the R-isomer of benzothiazole compounds requires a lower application rate to achieve the same weed control effect, demonstrating better environmental and ecological benefits.

[0178] In this invention, the term "weeds" should have the broadest or most general meaning, encompassing all types of plant species that are not desired to grow in undesirable locations. This invention categorizes "undesirable locations" into field crop growing areas and non-cultivated crop areas. Field crop growing areas refer to fields or open fields in the usual sense. Non-cultivated crop areas refer to locations other than field crop growing areas where weeds are not desired to grow, including vineyards, apple orchards, citrus orchards, banana plantations, coffee plantations, tea plantations, rubber plantations, oil palm plantations, coconut plantations, etc.

[0179] The 3,6-disubstituted benzothiazole compounds described in this invention can be used as a drug (such as a herbicide) or as an active ingredient in a drug, and are used in agriculture. Specifically, they are used to control broadleaf weeds and grass weeds in the following field crops.

[0180] Crop genera in the class Dicotyledonous plants include: Cotton, Soybean, Beetroot, Common Bean, Pea, Solanum, Flax, Tomato, Peanut, Brassica, Lettuce, Cantaloupe, Cucurbita, etc.

[0181] Crop genera in the monocotyledonous class include: rice, maize, wheat, barley, oats, millet, sugarcane, pineapple, asparagus, and allium.

[0182] Weed genera in the class Dicotyledonous plants include: *Sinapis*, *Mustard*, *Galium*, *Chilodon*, *Chenopodium*, *Kochia*, *Urtica*, *Senecio*, *Amaranthus*, *Portulaca*, *Xanthium*, *Ipomoea*, *Polygonum*, *Raphanus*, *Thistle*, *Sonchus*, *Solanum*, *Veronica*, *Datura*, *Viola*, *Papaver*, *Cornflower*, *Gnaphalium*, *Alternanthera*, *Heliotropium*, *Senecio*, *Trifolium*, *Abutilon*, *Sesamum*, *Heliotropium*, *Artemisia*, *Ipomoea*, etc.

[0183] Monocotyledonous weed genera include: barnyard grass, foxtail grass, millet, crabgrass, timothy grass, Kentucky bluegrass, woolly grass, ryegrass, bromegrass, oat, sedge, sorghum, icegrass, rainwort, sedge, arrowhead, burdock, paspalum, duckweed, creeping bentgrass, barnyardgrass, bermudagrass, dayflower, arm-shaped grass, and glehnia, etc.

[0184] Furthermore, the 3,6-disubstituted benzothiazole compounds of formula (I), and the herbicidal compositions (herbicides) thereof comprising the 3,6-disubstituted benzothiazole compounds of formula (I), can be used to control the following representative farmland weeds. The farmland weeds mentioned include common species such as: barnyard grass, pondweed, duckweed, sedge, flat-stemmed sugarcane grass, *Echinochloa crus-galli*, wild oats, crabgrass, cricket grass, foxtail grass, *Alopecurus aequalis*, shepherd's purse, shepherd's purse, *Hoopora sinensis*, knotweed, field bindweed, *Polygonum cuspidatum*, *Cyperus rotundus*, *Polygonum aviculare*, *Amaranthus retroflexus*, purslane, *Amaranthus urinaria*, dodder, *Abutilon theophrasti*, cleavers, *Gnaphalium affine*, *Ophiopogon japonicus*, *Xanthium sibiricum*, *Cynodon dactylon*, *Imperata cylindrica*, *Solanum nigrum*, *Stellaria media*, *Ageratum sibiricum*, *Artemisia argyi*, dandelion, *Erigeron annuus*, *Sonchus oleraceus*, *Artemisia capillaris*, *Sonchus oleraceus*, *Cirsium japonicum*, *Elsholtzia ciliata*, *Stachys aquifolium*, *Amaranthus tricolor*, etc.

[0185] Based on the herbicidal activity of the 3,6-disubstituted benzothiazole compound of formula (I) and its use as an agricultural herbicide, the present invention provides a herbicidal composition. The herbicidal composition contains the 3,6-disubstituted benzothiazole compound or a salt thereof, an agriculturally acceptable carrier and / or adjuvant, and a herbicide safener. Regarding the method of agricultural application of the herbicidal composition, the inventors have learned through experiments that applying it to the soil or weeds via pre-emergence soil treatment or post-emergence foliar spraying yields good herbicidal results.

[0186] As is readily apparent to those skilled in the art, achieving ideal weed control is influenced by a variety of factors. This is not only closely related to the specific dosage of the 3,6-disubstituted benzothiazole compound or its salt, but also to the crop to be protected, the weed to be controlled, the weed growth level, climatic conditions, application method, and formulation used. As mentioned above, a dosage of 1–500 g / ha is preferred, and the 3,6-disubstituted benzothiazole compound or its salt exhibits excellent pre- and post-emergence weed control activity. Under suitable temperature and light conditions, it maintains good weed control even at very low dosages.

[0187] More preferably, the amount of the 3,6-disubstituted benzothiazole compound or its salt used as the herbicidal composition is 1 to 150 g / ha. In the composition, the weight percentage of the 3,6-disubstituted benzothiazole compound or its salt is recommended to be between 0.1% and 99.0%.

[0188] Those skilled in the art will understand that the compositions provided by this invention, when used as agricultural herbicides, are typically used in agricultural applications in the form of formulations. The 3,6-disubstituted benzothiazole compounds or their salts are dissolved or dispersed in a carrier or formulated into suitable formulations for easier dispersion when used as herbicides. Herbicide formulations can be made into any of the following forms: wettable powder, water-dispersible granules, water-in-oil emulsions, dispersible oil suspensions, emulsifiable concentrates, or suspensions, but are not limited thereto. Those skilled in the art of formulation processing can select one or more suitable carriers or adjuvants to process them into agriculturally acceptable herbicide formulations.

[0189] Taking emulsifiable concentrates as an example, those skilled in the art are well aware of the use of appropriate emulsifiers or dispersion media to carry out this invention. Suitable nonionic emulsifiers include: Agricultural Emulsifier 700# (generic name: alkylphenol formaldehyde resin polyoxyethylene ether), Agricultural Emulsifier 2201, Span-60# (generic name: sorbitan stearate), Tween-60# (generic name: polyoxyethylene sorbitan stearate), Agricultural Emulsifier 1601# (generic name: triphenylethylphenol polyoxypropylene polyoxyethylene block polymer), and Tersperse. One or more of 4894; usable anionic emulsifiers such as calcium dodecylbenzenesulfonate, sodium dodecylbenzenesulfonate; usable dispersion media such as medium to high boiling point mineral oil fractions, such as kerosene, diesel oil; vegetable oils, such as soybean oil, rapeseed oil, cottonseed oil, corn oil, castor oil, palm oil, epoxidized soybean oil, methyl oleate and its methylated oils; aliphatic, cyclic and aromatic hydrocarbons, such as toluene, paraffin, tetrahydronaphthalene, alkyl naphthalene; alcohols, such as ethanol, propanol, butanol, benzyl alcohol, cyclohexanol; ketones, such as cyclohexanone; ester solvents such as dimethyl phthalate, dibutyl phthalate, ethyl acetate, methyl benzoate; and mixtures thereof.

[0190] Taking water-dispersible granules as an example, those skilled in the art are well aware of the use of appropriate carriers or additives to complete this invention. Dispersants include one or more of polycarboxylate salts (such as TERSPERSE 2700, T36, GY-D06, etc.), lignin sulfonates, and alkyl naphthalene sulfonates; wetting agents include one or more of alkyl sulfates, alkyl sulfonates, and naphthalene sulfonates; disintegrants include one or more of ammonium sulfate, urea, sucrose, and glucose; binders include one or more of diatomaceous earth, corn starch, polyvinyl alcohol (PVA), and carboxymethyl (ethyl) cellulose; the safety agent MON13900 (a product of Monsanto); and fillers include one or more of diatomaceous earth, kaolin, silica, light calcium carbonate, talc, attapulgite, and clay.

[0191] Taking wettable powder as an example, those skilled in the art are well aware of the use of appropriate carriers or additives to complete this invention. Dispersants that can be used include one or more of the following: polycarboxylates (TERSPERSE 2700, T36, GY-D06, etc.), lignin sulfonates (Ufoxane 3A, Borresperse NA, Borresperse CA-SA, etc.), naphthalene and alkylnaphthalene formaldehyde condensate sulfonates (NNO, MF, Morwet D-425, Tamol NN, TERSPERSE2020, etc.), separating powder BX (sodium dibutylnaphthalene sulfonate), EO-PO block polyethers, alkylphenol polyoxyethylene ether phosphates, and alkylphenol polyoxyethylene ether formaldehyde condensate sulfates (SOPA); wetting agents include sulfates (K-12), sulfonates (ABS-Na, BX, Terwet1004, etc.), and composite wetting agents (Morwet...). One or more of EFW; fillers such as diatomaceous earth, kaolin, light calcium carbonate, talc, silica, attapulgite, clay, ammonium sulfate, urea, sucrose, glucose, corn starch, sodium sulfate, sodium polyphosphate, etc.

[0192] Taking dispersible oil suspensions as an example, those skilled in the art are well aware of the use of appropriate carriers or additives to complete this invention. Dispersants such as polycarboxylate, lignin sulfonate, alkyl naphthalene sulfonate (dispersant NNO), and TERSPERSE 2020 (alkyl naphthalene sulfonate) or one or more can be used; emulsifiers such as Agricultural Emulsion 700# (generic name: alkylphenol formaldehyde resin polyoxyethylene ether), Agricultural Emulsion 2201, Span-60# (generic name: dehydrated sorbitan stearate), Tween-60# (generic name: polyoxyethylene dehydrated sorbitan stearate), Agricultural Emulsion 1601# (generic name: triphenylethylphenol polyoxypropylene polyoxyethylene block polymer), and TERSPERSE 4894 or one or more can be used; wetting agents such as alkylphenol polyoxyethylene ether formaldehyde condensate sulfate, alkylphenol polyoxyethylene ether phosphate, phenylethylphenol polyoxyethylene ether phosphate, alkyl sulfate, alkyl sulfonate, naphthalene sulfonate, and TERSPERSE can be used. One or more of the following: 2500; one or more thickeners such as xanthan gum, polyvinyl alcohol, bentonite, and magnesium aluminum silicate; one or more preservatives such as formaldehyde, benzoic acid, and sodium benzoate; safety agent MON13900; defoamer such as silicone defoamer; antifreeze such as ethylene glycol, propylene glycol, glycerin, urea, and one or more inorganic salts such as sodium chloride; and deionized water.

[0193] Taking suspending agents as an example, the dispersants selected include one or more of polycarboxylate, lignin sulfonate, alkyl naphthalene sulfonate (dispersant NNO), and TERSPERSE 2020 (alkyl naphthalene sulfonate); the emulsifiers selected include BY (castor oil polyoxyethylene ether) series emulsifiers (BY-110, BY-125, BY-140), agricultural emulsion 700# (common name: alkylphenol formaldehyde resin polyoxyethylene ether), agricultural emulsion 2201, Span-60# (common name: sorbitan monostearate), Tween-60# (common name: dehydrated sorbitan monostearate polyoxyethylene ether), agricultural emulsion 1601# (common name: phenethylphenol polyoxyethylene polyoxypropylene ether), and TERSPERSE. One or more of 4894; wetting agents such as alkylphenol polyoxyethylene ether formaldehyde condensate sulfate, alkylphenol polyoxyethylene ether phosphate, phenethylphenol polyoxyethylene ether phosphate, alkyl sulfate, alkyl sulfonate, naphthalene sulfonate, TERSPERSE 2500 (produced by Huntsman Corporation, USA) or one or more; thickeners such as silica, polyvinyl alcohol, bentonite, magnesium aluminum silicate or one or more; safety agent MON13900; antifreeze agents such as ethylene glycol, propylene glycol, glycerin, urea, inorganic salts such as sodium chloride or one or more; dispersion media such as soybean oil, rapeseed oil, cottonseed oil, corn oil, castor oil, palm oil, epoxidized soybean oil, methyl oleate and its methylated oils, diesel oil, engine oil, mineral oil, and ester solvents such as dimethyl phthalate, dibutyl phthalate, ethyl acetate, methyl benzoate or one or more.

[0194] In the field of herbicide technology, herbicide safeners can be selectively added as adjuvant components to herbicide compositions. One or more of the following compounds a) to i) can be used as herbicide safeners for the herbicide compositions of the present invention.

[0195] a) Dichlorophenylpyrazoline-3-carboxylic acid compounds, such as ethyl 1-(2,4-dichlorophenyl)-5-(ethoxycarbonyl)-5-methyl-2-pyrazoline-3-carboxylic acid, i.e. mefenpyrdi-ethyl.

[0196] b) Dichlorophenylpyrazole carboxylic acid derivatives, such as ethyl 1-(2,4-dichlorophenyl)-5-methylpyrazole-3-carboxylate, ethyl 1-(2,4-dichlorophenyl)-5-isopropylpyrazole-3-carboxylate, ethyl 1-(2,4-dichlorophenyl)-5-(1,1-dimethyl-ethyl)pyrazole-3-carboxylate, and ethyl 1-(2,4-dichlorophenyl)-5-phenylpyrazole-3-carboxylate.

[0197] c) Triazole carboxylic acid compounds, such as fenchlorazole-ethyl, i.e., ethyl 1-(2,4-dichlorophenyl)-5-trichloromethyl-(1H)-1,2,4-triazole-3-carboxylate.

[0198] d) 5-Benzyl or 5-phenyl-2-isooxazoline-3-carboxylic acid or 5,5-diphenyl-2-isooxazoline-3-carboxylic acid compounds, such as ethyl 4,5-dihydro-5,5-diphenyl-1,2-azole-3-carboxylic acid, i.e., isoxadifen-ethyl, ethyl 5-(2,4-dichlorobenzyl)-2-isooxazoline-3-carboxylic acid, or ethyl 5-phenyl-2-isooxazoline-3-carboxylic acid.

[0199] e) 8-Quinolinoxyacetic acid compounds, such as 1-methylhexane-1-yl(5-chloro-8-quinolinoxy)acetate, i.e., cloquintocet-mexyl, (1,3-dimethylbut-1-yl)(5-chloro-8-quinolinoxy)acetate, 4-allyloxybutyl(5-chloro-8-quinolinoxy)acetate, 1-allyloxypropyl-2-yl(5-chloro-8-quinolinoxy)acetate, ethyl acetate (5-chloro-8-quinolinoxy), methyl acetate (5-chloro-8-quinolinoxy), and allyl acetate (5-chloro-8-quinolinoxy).

[0200] f)(5-chloro-8-quinolinoxy)malonic acid compounds, such as diethyl (5-chloro-8-quinolinoxy)malonic acid, diallyl (5-chloro-8-quinolinoxy)malonic acid, and methyl ethyl (5-chloro-8-quinolinoxy)malonic acid.

[0201] g) Phenoxyacetic acid, phenoxypropionic acid or aromatic carboxylic acid compounds, such as 2,4-dichlorophenoxyacetic acid or its esters (e.g., 2,4-D), 4-chloro-2-methylphenoxypropionate (e.g., 2-methyl-4-chloropropionic acid), MCPA or 3,6-dichloro-2-methoxybenzoic acid or its esters (e.g., dicamba).

[0202] h) Pyrimidine compounds, for example, fenclorim.

[0203] i) Dichloroacetamide compounds, such as N,N-diallyl-2,2-dichloroacetamide, i.e., dichloropropenylamine, 3-dichloroacetyl-2,2,5-trimethyl-1,3-oxazolidinone, and 4-dichloroacetyl-3,4-dihydro-3-methyl-2H-1,4-benzoxazine, i.e., benoxacor.

[0204] Compared with the prior art, the beneficial effects or advantages of the present invention are as follows:

[0205] This invention is the first to present the chemical structure of 3,6-disubstituted benzothiazole compounds or their salts as described in formula (I), herbicide compositions thereof, and their uses in weed control.

[0206] The present invention further provides a synthetic preparation process for the 3,6-disubstituted benzothiazole compounds, which uses widely available and inexpensive raw materials, has a short synthetic route, simple post-reaction processing, high yield, and is easy to realize on a large scale in industrial production.

[0207] The 3,6-disubstituted benzothiazole compounds or their salts are used to control weeds in field crop growing areas and non-cultivated crop areas. They are characterized by rapid action and high herbicidal activity, and can be used to control weeds resistant to existing herbicides, especially those resistant to ALS inhibitors, PSII inhibitors, ACCase inhibitors, and EPSP inhibitors. When used as a component of a herbicidal composition, the 3,6-disubstituted benzothiazole compounds or their salts also show good control effects on weeds in field crop growing areas and non-cultivated crop areas. This fully demonstrates that the 3,6-disubstituted benzothiazole compounds or their salts have excellent development potential in the development of new herbicides, providing a new approach for the development and creation of new green chemical pesticides.

[0208] The composition of the 3,6-disubstituted benzothiazole compounds or their salts can be processed into various formulations such as emulsifiable concentrates, suspension concentrates, water-dispersible granules, wettable powders, or dispersible oil suspensions that meet the needs of agricultural production. It also has good safety for crops and meets the safety requirements of pesticide formulations.

[0209] The 3,6-disubstituted benzothiazole compounds or their salts, and their preparation as herbicides (herbicidal compositions), exhibit excellent herbicidal activity against a variety of weeds and demonstrate good safety for crops such as wheat, rice, and corn. This invention provides an effective solution for the control of resistant weeds. Attached Figure Description

[0210] Figure 1 This is a single-crystal diffraction structure of the intermediate 3-(3-chloro-5-(trifluoromethyl)pyridin-2-yl)-6-methoxybenzothiazol-2(3H)-one (IV-A). Detailed Implementation

[0211] To facilitate understanding of the purpose, technical solution, and effects of this invention, the invention will now be further described in detail with reference to the embodiments.

[0212] Compound Synthesis Examples

[0213] Example 1: Preparation of intermediate 6-methoxybenzothiazol-2(3H)-one (V)

[0214] Weigh 384 g of 30% hydrochloric acid and add it to a 2000 mL three-necked flask. Add 54.0 g (0.3 mol) of 2-amino-6-methoxybenzothiazole (VIII) and 35.2 g (0.32 mol) of anhydrous calcium chloride while stirring at room temperature. Stir the reaction mixture at 50 °C for 30 min, then cool to 20 °C and add 86.3 g (0.5 mol) of 40% sodium nitrite solution dropwise. After the addition is complete, continue stirring for 5 h, maintaining the temperature at 20–25 °C. After the reaction is complete as determined by thin-layer chromatography, add 20 g of 50% urea solution to destroy excess nitrite in the reaction system. The generated 2-chloro-6-methoxybenzothiazole (VII) does not need to be separated; simply add 600 mL of methanol to the three-necked flask and reflux the reaction mixture for 2–3 h. Thin-layer chromatography will then show the disappearance of intermediate product VII. Excess methanol in the reaction system was removed by vacuum distillation. The remaining solution was filtered while hot, and crystals precipitated from the filtrate at room temperature, which was 6-methoxybenzothiazol-2(3H)-one (V) with a purity of 98% and a yield of 85%.

[0215] Example 2 Preparation of intermediate 3-(3-chloro-5-(trifluoromethyl)pyridin-2-yl)-6-methoxybenzothiazol-2(3H)-one (IV-A)

[0216] In a 100 mL three-necked flask, 276 mg (2.0 mmol) of anhydrous K₂CO₃, 5.0 mL of dry DMF solution, and 181 mg (1.0 mmol) of 6-methoxybenzothiazol-2(3H)-one (V) were added sequentially. The mixture was stirred in an oil bath at 80 °C for 30 min, followed by the addition of 238 mg (1.1 mmol) of 2,3-dichloro-5-trifluoromethylpyridine (VI-A). The mixture was stirred in an oil bath at 110 °C for 12 h. The reaction mixture was cooled, and the pH was adjusted to 2–3 with 1.0 M hydrochloric acid. Extraction was performed with ethyl acetate (3 × 20 mL). The organic layer was washed with brine (3 × 20 mL), dried over anhydrous sodium sulfate, and concentrated under reduced pressure to obtain the crude sample. Recrystallization from the crude sample with ethanol yielded 340 mg of the final product with a purity of 98% and a yield of 94.4%. 1 HNMR(400MHz, CDCl3), δ:8.84(d,J=1.6Hz,1H),8.23(d,J=2.4Hz,1H),7.03(d,J=2 .8Hz,1H),6.79(dd,J=8.8,2.4Hz,1H),6.62(d,J=8.8Hz,1H),3.80(s,3H).HRMS:C 14 H9ClF3N2O2S[M+H] + Calculated value: 361.0025, Measured value: 361.0032.

[0217] The single-crystal diffraction structure of intermediate IV-A is shown in Figure 1. Figure 1 .

[0218]

[0219] Example 3 Preparation of intermediate 3-(3-fluoro-5-(trifluoromethyl)pyridin-2-yl)-6-methoxybenzothiazol-2(3H)-one (IV-B)

[0220] In a 100 mL pear-shaped flask, 276 mg (2.0 mmol) of anhydrous K₂CO₃, 5.0 mL of dry DMF solution, and 181 mg (1.0 mmol) of 6-methoxybenzothiazol-2(3H)-one (V) were added sequentially. The mixture was stirred in an oil bath at 80 °C for 30 min, followed by the addition of 201 mg (1.1 mmol) of 2,3-difluoro-5-trifluoromethylpyridine (VI-B). The mixture was stirred in an oil bath at 110 °C for 12 h. The reaction mixture was cooled, and the pH was adjusted to 2–3 with 1.0 M hydrochloric acid. Extraction was performed with ethyl acetate (3 × 20 mL). The organic layer was washed with brine (3 × 20 mL), dried over anhydrous sodium sulfate, and concentrated under reduced pressure to obtain the crude sample. Recrystallization from the crude sample with ethanol yielded 296 mg of the final product, with a yield of 86.1%. 1H NMR (500MHz, CDCl3), δ: 8.77 (d, J = 2.5Hz, 1H), 7.91 (dd, J = 8.5, 2.0Hz, 1H), 7.05 (d, J =2.0Hz,1H),6.88(d,J=8.5Hz,1H),6.81(dd,J=8.5,2.0Hz,1H),3.79(s,3H).HRMS:C 14 H9F4N2O2S[M+H] + Calculated value: 345.0321, Measured value: 345.0320.

[0221]

[0222] Example 4: Preparation of intermediate 6-methoxy-3-(5-(trifluoromethyl)pyridin-2-yl)benzothiazol-2(3H)-one (IV-C)

[0223] In a 100 mL pear-shaped flask, 276 mg (2.0 mmol) of anhydrous K₂CO₃, 5.0 mL of dry DMSO solution, and 181 mg (1.0 mmol) of 6-methoxybenzothiazol-2(3H)-one (V) were added sequentially. The mixture was stirred in an oil bath at 80 °C for 30 min, followed by the addition of 199 mg (1.1 mmol) of 2-chloro-5-trifluoromethylpyridine (VI-C). The mixture was stirred in an oil bath at 140 °C for 12 h. The reaction mixture was cooled, and the pH was adjusted to 2–3 with 1.0 M hydrochloric acid. Extraction was performed with ethyl acetate (3 × 20 mL). The organic layer was washed with brine (3 × 20 mL), dried over anhydrous sodium sulfate, and concentrated under reduced pressure to obtain the crude sample. Recrystallization from the crude sample with ethanol yielded 232 mg of the final product, with a yield of 71.3%. 1 H NMR (500MHz, CDCl3), δ: 8.87 (d, J = 2.0Hz, 1H), 8.15 (dd, J = 8.5, 2.5Hz, 1H), 7.86 (d, J = 8.5Hz, 1H ),7.46(d,J=8.5Hz,1H),7.01(d,J=2.5Hz,1H),6.82(dd,J=8.5,2.5Hz,1H),3.81(s,3H).HRMS:C 14 H 10 F3N2O2S[M+H] + Calculated value: 327.0415, Measured value: 327.0412.

[0224]

[0225] Example 5 Preparation of intermediate 3-(3-chloro-5-(trifluoromethyl)pyridin-2-yl)-6-hydroxybenzothiazol-2(3H)-one (II-A)

[0226] 180 mg (0.5 mmol) of 2-(3-chloro-5-(trifluoromethyl)pyridin-2-oxy)-6-methoxybenzothiazole (IV-A) and 5.0 mL of 48% HBr solution were added to a 100 mL pear-shaped flask, and the mixture was refluxed in an oil bath at 110 °C for 12 h. The reaction mixture was cooled, diluted with 20 mL of water, and extracted with ethyl acetate (3 × 20 mL). The organic layer was washed with brine (3 × 20 mL), dried over anhydrous sodium sulfate, and concentrated under reduced pressure to obtain a crude sample. The crude sample was recrystallized from ethanol to give 149 mg of the final product, with a yield of 85.9%. 1 H NMR (400MHz, CDCl3), δ: 8.84 (d, J = 1.2Hz, 1H), 8.23 ​​(d, J = 2.0Hz, 1H), 6.96 (d, J = 2.8Hz, 1H), 6.71 (dd, J = 8.8, 2.4Hz, 1H), 6.55 (d, J = 8.8Hz, 1H). HRMS: C 13 H7ClF3N2O2S[M+H] + Calculated value: 346.9869, Measured value: 346.9872.

[0227]

[0228] Example 6 Preparation of intermediate 3-(3-fluoro-5-(trifluoromethyl)pyridin-2-yl)-6-hydroxybenzothiazol-2(3H)-one (II-B)

[0229] 172 mg (0.5 mmol) of 2-(3-fluoro-5-(trifluoromethyl)pyridin-2-oxy)-6-methoxybenzothiazole (IV-B) and 5.0 mL of 48% HBr solution were added to a 100 mL pear-shaped flask, and the mixture was refluxed in an oil bath at 110 °C for 12 h. The reaction mixture was cooled, diluted with 20 mL of water, and extracted with ethyl acetate (3 × 20 mL). The organic layer was washed with brine (3 × 20 mL), dried over anhydrous sodium sulfate, and concentrated under reduced pressure to obtain a crude sample. The crude sample was recrystallized from ethanol to give 136 mg of the final product, with a yield of 82.7%. 1 H NMR (500MHz, CDCl3), δ: 8.76 (d, J = 2.5 Hz, 1H), 7.94 (dd, J = 8.5, 2.0 Hz, 1H), 7.03 (d, J = 2.0 Hz, 1H), 6.88 (d, J = 8.5 Hz, 1H), 6.81 (dd, J = 8.5, 2.0 Hz, 1H). HRMS: C 13 H7F4N2O2S[M+H] + Calculated value: 331.0164, Measured value: 331.0160.

[0230]

[0231] Example 7 Preparation of intermediate 6-hydroxy-3-(5-(trifluoromethyl)pyridin-2-yl)benzothiazol-2(3H)-one (II-C)

[0232] 163 mg (0.5 mmol) of 2-(5-(trifluoromethyl)pyridin-2-oxy)-6-methoxybenzothiazole (IV-C) and 5.0 mL of 48% HBr solution were added to a 100 mL pear-shaped flask, and the mixture was refluxed in an oil bath at 110 °C for 12 h. The reaction mixture was cooled, diluted with 20 mL of water, and extracted with ethyl acetate (3 × 20 mL). The organic layer was washed with brine (3 × 20 mL), dried over anhydrous sodium sulfate, and concentrated under reduced pressure to obtain a crude sample. The crude sample was recrystallized from ethanol to give 136 mg of the final product, with a yield of 87.1%. 1 HNMR (500MHz, CDCl3), δ: 8.86 (d, J = 2.0Hz, 1H), 8.14 (dd, J = 8.5, 2.5Hz, 1H), 7.85 (d, J = 8. 5Hz,1H),7.46(d,J=8.5Hz,1H),7.03(d,J=2.5Hz,1H),6.82(dd,J=8.5,2.5Hz,1H).HRMS:C 13 H8F3N2O2S[M+H] + Calculated value: 313.0259, Measured value: 313.0255.

[0233]

[0234] Example 8 Preparation of compound 2-(3-(3-chloro-5-(trifluoromethyl)pyridin-2-yl)-2-oxo-2,3-dihydrobenzothiazol-6-oxy)propionate (IAa02)

[0235] In a 100 mL pear-shaped flask, 276 mg (2.0 mmol) of anhydrous K₂CO₃, 5.0 mL of dry DMF solution, and 346 mg (1.0 mmol) of 3-(3-chloro-5-(trifluoromethyl)pyridin-2-yl)-6-hydroxybenzothiazol-2(3H)-one (II-A) were added sequentially. The mixture was stirred in an oil bath at 80 °C for 30 min, followed by the addition of 144 mg (1.2 mmol) of methyl 2-chloropropionate. The mixture was stirred in an oil bath at 110 °C for 12 h. The reaction mixture was cooled, and the pH was adjusted to 2–3 with 1.0 M hydrochloric acid. Extraction was performed with ethyl acetate (3 × 20 mL). The organic layer was washed with brine (3 × 20 mL), dried over anhydrous sodium sulfate, and concentrated under reduced pressure to obtain the crude sample. Purification by silica gel column chromatography (petroleum ether:ethyl acetate = 7:1) yielded 361 mg of the target compound, with a yield of 83.6%. 1H NMR(400MHz, CDCl3), δ:8.84(d,J=1.2Hz,1H),8.23(d,J=1.2Hz,1H),7.03(dd,J=6.0,2.4Hz,1H),6.78-6 .82(m,1H),6.62(dd,J=8.8,1.2Hz,1H),4.74(q,J=6.8Hz,1H),3.76(s,3H),1.63(d,J=6.8Hz,3H).HRMS:C 17 H 13 ClF3N2O4S[M+H] + Calculated value: 433.0237, Measured value: 433.0242.

[0236]

[0237] Example 9 Preparation of compound methyl 2-(2-oxo-3-(5-(trifluoromethyl)pyridin-2-yl)-2,3-dihydrobenzothiazol-6-oxy)propionate (ICaO2)

[0238] In a 100 mL pear-shaped flask, 276 mg (2.0 mmol) of anhydrous K₂CO₃, 5.0 mL of dry DMF solution, and 312 mg (1.0 mmol) of 6-hydroxy-3-(5-(trifluoromethyl)pyridin-2-yl)benzothiazol-2(3H)-one (II-C) were added sequentially. The mixture was stirred in an oil bath at 80 °C for 30 min, followed by the addition of 144 mg (1.2 mmol) of methyl 2-chloropropionate. The mixture was stirred in an oil bath at 110 °C for 12 h. The reaction mixture was cooled, and the pH was adjusted to 2–3 with 1.0 M hydrochloric acid. Extraction was performed with ethyl acetate (3 × 20 mL). The organic layer was washed with brine (3 × 20 mL), dried over anhydrous sodium sulfate, and concentrated under reduced pressure to obtain the crude sample. Purification by silica gel column chromatography (petroleum ether:ethyl acetate = 7:1) yielded 324 mg of the target compound, with a yield of 81.5%. 1 H NMR (500MHz, CDCl3), δ: 8.89 (d, J = 2.0Hz, 1H), 8.15 (dd, J = 8.5, 2.5Hz, 1H), 7.87 (d, J = 8.5Hz, 1H), 7.46 (d, J = 8.5Hz, 1H ),7.01(d,J=2.5Hz,1H),6.84(dd,J=8.5,2.5Hz,1H),4.75(q,J=7.0Hz,1H),3.76(s,3H),1.65(d,J=6.8Hz,3H).HRMS:C 17 H 14 F3N2O4S[M+H] + Calculated value: 399.0626, Measured value: 399.0630.

[0239]

[0240] Example 102: Preparation of methyl propionate (IBaO2) 2-(3-(3-fluoro-5-(trifluoromethyl)pyridin-2-yl)-2-oxo-2,3-dihydrobenzothiazol-6-oxy)propionate

[0241] In a 100 mL pear-shaped flask, 276 mg (2.0 mmol) of anhydrous K₂CO₃, 5.0 mL of dry DMF solution, and 330 mg (1.0 mmol) of 3-(3-fluoro-5-(trifluoromethyl)pyridin-2-yl)-6-hydroxybenzothiazol-2(3H)-one (II-B) were added sequentially. The mixture was stirred in an oil bath at 80 °C for 30 min, followed by the addition of 144 mg (1.2 mmol) of methyl 2-chloropropionate. The mixture was stirred in an oil bath at 110 °C for 12 h. The reaction mixture was cooled, and the pH was adjusted to 2–3 with 1.0 M hydrochloric acid. Extraction was performed with ethyl acetate (3 × 20 mL). The organic layer was washed with brine (3 × 20 mL), dried over anhydrous sodium sulfate, and concentrated under reduced pressure to obtain the crude sample. Purification by silica gel column chromatography (petroleum ether:ethyl acetate = 7:1) yielded 350 mg of the target compound, with a yield of 84.1%. 1 H NMR (500MHz, CDCl3), δ: 8.76 (d, J = 2.5Hz, 1H), 7.94 (dd, J = 8.5, 2.0Hz, 1H), 7.02 (d, J = 2.0Hz, 1H), 6.89 (d, J =8.5Hz,1H),6.82(dd,J=8.5,2.0Hz,1H),4.75(q,J=7.0Hz,1H),3.76(s,3H),1.62(d,J=7.0Hz,3H).HRMS:C 17 H 13 F4N2O4S[M+H] + Calculated value: 417.0532, Measured value: 417.0533.

[0242]

[0243] Example 112: Preparation of ethyl (IAbO3) 2-(3-(3-chloro-5-(trifluoromethyl)pyridin-2-yl)-2-oxo-2,3-dihydrobenzothiazol-6-oxy)butyrate (IAbO3)

[0244] In a 100 mL pear-shaped flask, 276 mg (2.0 mmol) of anhydrous K₂CO₃, 5.0 mL of dry DMF solution, and 346 mg (1.0 mmol) of 3-(3-chloro-5-(trifluoromethyl)pyridin-2-yl)-6-hydroxybenzothiazol-2(3H)-one (II-A) were added sequentially. The mixture was stirred in an oil bath at 80 °C for 30 min, followed by the addition of 234 mg (1.2 mmol) of ethyl 2-bromobutyrate. The mixture was stirred in an oil bath at 110 °C for 12 h. The reaction mixture was cooled, and the pH was adjusted to 2–3 with 1.0 M hydrochloric acid. Extraction was performed with ethyl acetate (3 × 20 mL). The organic layer was washed with brine (3 × 20 mL), dried over anhydrous sodium sulfate, and concentrated under reduced pressure to obtain the crude sample. Purification by silica gel column chromatography (petroleum ether:ethyl acetate = 7:1) yielded 419 mg of the target compound, with a yield of 91.2%. 1 H NMR (400MHz, CDCl3), δ: 8.84 (d, J = 1.2Hz, 1H), 8.23 ​​(d, J = 2.0Hz, 1H), 7.03 (dd, J = 4.0, 2.8Hz, 1H), 6.79-6.83 (m, 1H), 6.62 (d, J=8.8,1H),4.52(t,J=6.0Hz,1H),4.21(q,J=7.2Hz,2H),1.96-2.03(m,2H),1.24-1.28(m,3H),1.08(t,J=7.2Hz,3H).HRMS:C 19 H 17 ClF3N2O4S[M+H] + Calculated value: 461.0550, Measured value: 461.0552.

[0245]

[0246] Example 122: Preparation of methyl hexanoate (IAd02) of 2-(3-(3-chloro-5-(trifluoromethyl)pyridin-2-yl)-2-oxo-2,3-dihydrobenzothiazol-6-oxy)

[0247] In a 100 mL pear-shaped flask, 276 mg (2.0 mmol) of anhydrous K₂CO₃, 5.0 mL of dry DMF solution, and 346 mg (1.0 mmol) of 3-(3-chloro-5-(trifluoromethyl)pyridin-2-yl)-6-hydroxybenzothiazol-2(3H)-one (II-A) were added sequentially. The mixture was stirred in an oil bath at 80 °C for 30 min, followed by the addition of 249 mg (1.2 mmol) of methyl 2-bromohexanoate. The mixture was stirred in an oil bath at 110 °C for 12 h. The reaction mixture was cooled, and the pH was adjusted to 2–3 with 1.0 M hydrochloric acid. Extraction was performed with ethyl acetate (3 × 20 mL). The organic layer was washed with brine (3 × 20 mL), dried over anhydrous sodium sulfate, and concentrated under reduced pressure to obtain the crude sample. Purification by silica gel column chromatography (petroleum ether:ethyl acetate = 7:1) yielded 398 mg of the target compound, with a yield of 84.1%. 1 H NMR (500MHz, CDCl3), δ: 8.84 (d, J = 2.0Hz, 1H), 8.23 ​​(d, J = 2.0Hz, 1H), 7.03 (dd, J = 6.0, 2.0Hz, 1H), 6.78-6.81 (m, 1H), 6.62 (d d,J=9.0,2.0Hz,1H),4.57(t,J=7.0Hz,1H),3.75(s,3H),1.92-1.98(m,2H),1.34-1.58(m,4H),0.92(t,J=7.0Hz,3H).HRMS:C 20 H 19 ClF3N2O4S[M+H] + Calculated value: 475.0706, Measured value: 475.0698.

[0248]

[0249] Example 132-(3-(3-chloro-5-(trifluoromethyl)pyridin-2-yl)-2-oxo-2,3-benzothiazo-6-oxy)hexanoic acid-2-ethoxyethyl ester (IAd46)

[0250] (1) Preparation of 2-bromohexanoic acid-2-ethoxyethyl ester: In a 100 mL pear-shaped flask, 90 mg (1.0 mmol) of ethylene glycol ethyl ether, 130 mg (1.3 mmol) of triethylamine and 5.0 mL of dry dichloromethane were added. The mixture was cooled to 0 °C in an ice bath, and 254 mg (1.2 mmol) of a dichloromethane solution of 2-bromohexanoyl chloride was slowly added dropwise with stirring, keeping the temperature below 0 °C. After the addition was complete, the mixture was stirred at room temperature for 5 h. The reaction solution was poured into 10 mL of ice water and extracted with dichloromethane (3 × 20 mL). The organic phases were combined, washed with saturated sodium carbonate solution, washed with water, dried over anhydrous sodium sulfate, and concentrated under reduced pressure to obtain 240 mg of a pale yellow oily substance, with a yield of 90.0%. No separation was required, and the next reaction was carried out directly.

[0251]

[0252] (2) Preparation of IAd46: 276 mg (2.0 mmol) of anhydrous K₂CO₃, 5.0 mL of dry DMF solution, and 346 mg (1.0 mmol) of 3-(3-chloro-5-(trifluoromethyl)pyridin-2-yl)-6-hydroxybenzothiazol-2(3H)-one (II-A) were added sequentially to a 100 mL pear-shaped flask. After stirring in an oil bath at 80 °C for 30 min, 319 mg (1.2 mmol) of 2-bromohexanoic acid-2-ethoxyethyl ester was added, and the mixture was stirred in an oil bath at 110 °C for 12 h. The reaction mixture was cooled, and the pH was adjusted to 2–3 with 1.0 M hydrochloric acid. Extraction was performed with ethyl acetate (3 × 20 mL). The organic layer was washed with brine (3 × 20 mL), dried over anhydrous sodium sulfate, and concentrated under reduced pressure to obtain the crude sample. Purification by silica gel column chromatography (petroleum ether:ethyl acetate = 7:1) yielded 416 mg of the target compound, with a yield of 78.2%. 1 HNMR (500MHz, CDCl3), δ: 8.84 (d, J = 2.5Hz, 1H), 8.23 ​​(d, J = 2.5Hz, 1H), 7.03 (dd, J=9.0,2.5Hz,1H),6.80-6.84(m,1H),6.62(dd,J=9.0,2.5Hz,1H),4.75(t,J=6. 5Hz,1H),4.60-4.63(m,2H),4.31-4.34(m,2H),3.49(q,J=5.5Hz,2H),1.92-1.9 8(m,2H),1.34-1.58(m,4H),1.17(t,J=7.0Hz,3H),0.92(t,J=7.0Hz,3H).HRMS:C 23 H 25 ClF3N2O5S[M+H] + Calculated value: 533.1125, Measured value: 533.1128.

[0253]

[0254] Example 14: Preparation of 2-isopropylaminooxyethyl-2-(3-(3-chloro-5-(trifluoromethyl)pyridin-2-yl)-2-oxo-2,3-dihydrobenzothiazol-6-oxy)hexanoate (IAd14)

[0255] (1) Preparation of 2-[(isopropylamino)oxy]ethanol: 300 mg of acetone oxime (4.1 mmol) and 20 mL of dry methanol were added to a 100 mL pear-shaped flask. The mixture was cooled to 0 °C in an ice-salt bath, and 244 mg of sodium methoxide (4.51 mmol) was added in portions. After stirring at 0 °C for 20 min, ethylene oxide (199 mg, 4.51 mmol) was slowly added dropwise. After the addition was complete, the mixture was slowly heated to room temperature and stirred for 12 h. The pH of the reaction mixture was adjusted to neutral by adding an appropriate amount of acetic acid. After removing methanol by concentration under reduced pressure, 50 mL of water was added, and the mixture was extracted with ethyl acetate (3 × 20 mL). The organic layer was washed with brine (3 × 20 mL), dried over anhydrous sodium sulfate, and concentrated under reduced pressure to obtain 320 mg of crude sample, with a yield of 77.3%. No separation was required, and the next reaction was carried out directly.

[0256]

[0257] (2) Preparation of (2-isopropylaminooxyethyl)-2-bromohexanoate: In a 100 mL pear-shaped flask, 101 mg (1.0 mmol) of 2-[(isopropylamino)oxy]ethanol, 130 mg (1.3 mmol) of triethylamine, and 5.0 mL of dry dichloromethane were added. The mixture was cooled to 0 °C in an ice bath, and 254 mg (1.2 mmol) of a dichloromethane solution of 2-bromohexanoyl chloride was slowly added dropwise with stirring, keeping the temperature below 0 °C. After the addition was complete, the mixture was stirred at room temperature for 5 h. The reaction solution was poured into 10 mL of ice water and extracted with dichloromethane (3 × 20 mL). The organic phases were combined, washed with saturated sodium carbonate solution, washed with water, dried over anhydrous sodium sulfate, and concentrated under reduced pressure to obtain 248 mg of a pale yellow oil, with a yield of 84.5%. No separation was required, and the reaction proceeded directly to the next step.

[0258]

[0259] (3) Preparation of IAd14: 276 mg (2.0 mmol) of anhydrous K₂CO₃, 5.0 mL of dry DMF solution, and 346 mg (1.0 mmol) of 3-(3-chloro-5-(trifluoromethyl)pyridin-2-yl)-6-hydroxybenzothiazol-2(3H)-one (II-A) were added sequentially to a 100 mL pear-shaped flask. After stirring in an oil bath at 80 °C for 30 min, 352 mg (1.2 mmol) of (2-isopropylaminooxyethyl)-2-bromohexanoate was added, and the mixture was stirred in an oil bath at 110 °C for 12 h. The reaction mixture was cooled, and the pH was adjusted to 2–3 with 1.0 M hydrochloric acid. Extraction was performed with ethyl acetate (3 × 20 mL). The organic layer was washed with brine (3 × 20 mL), dried over anhydrous sodium sulfate, and concentrated under reduced pressure to obtain the crude sample. Purification by silica gel column chromatography (petroleum ether:ethyl acetate = 7:1) yielded 475 mg of the target compound, with a yield of 85.0%. 1H NMR (500MHz, CDCl3), δ: 8.84 (d, J = 2.0Hz, 1H), 8.23 ​​(d, J = 2.0Hz, 1H), 7.03 (dd, J = 6.0, 2.0Hz, 1H), 6.78-6.81 (m, 1H), 6.62 (dd, J = 9.0, 2.0Hz, 1H), 4.57 (q,J=7.0Hz,1H),4.07-4.15(m,2H),3.76-3.86(m,2H),1.92-1.98(m,2H), 1.87(s,3H),1.84(s,3H),1.34-1.58(m,4H),0.92(t,J=7.0Hz,3H).HRMS:C 24 H 26 ClF3N3O5S[M+H] + Calculated value: 560.1234, Measured value: 560.1240.

[0260]

[0261] Example 15: Preparation of 2-(3-(3-chloro-5-(trifluoromethyl)pyridin-2-yl)-2-oxo-2,3-dihydrobenzothiazo-6-oxy)hexanoate tetrahydrofuran-2-methyl ester (IAd09)

[0262] (1) Preparation of tetrahydrofuran-2-methyl 2-bromohexanoate: In a 100 mL pear-shaped flask, 102 mg (1.0 mmol) tetrahydrofurfuryl alcohol, 130 mg (1.3 mmol) triethylamine, and 5.0 mL of dry dichloromethane were added. The mixture was cooled to 0 °C in an ice bath, and 254 mg (1.2 mmol) of a dichloromethane solution of 2-bromohexanoyl chloride was slowly added dropwise with stirring, keeping the temperature below 0 °C. After the addition was complete, the mixture was stirred at room temperature for 5 h. The reaction solution was poured into 10 mL of ice water and extracted with dichloromethane (3 × 20 mL). The organic phases were combined, washed with saturated sodium carbonate solution, washed with water, dried over anhydrous sodium sulfate, and concentrated under reduced pressure to obtain 243 mg of a pale yellow oil, with a yield of 87.3%. No separation was required, and the next reaction was carried out directly.

[0263]

[0264] (2) Preparation of IAd09: 276 mg (2.0 mmol) of anhydrous K₂CO₃, 5.0 mL of dry DMF solution, and 346 mg (1.0 mmol) of 3-(3-chloro-5-(trifluoromethyl)pyridin-2-yl)-6-hydroxybenzothiazol-2(3H)-one (II-A) were added sequentially to a 100 mL pear-shaped flask. After stirring in an oil bath at 80 °C for 30 min, 334 mg (1.2 mmol) of the preparation of tetrahydrofuran-2-methyl 2-bromohexanoate was added, and the mixture was stirred in an oil bath at 110 °C for 12 h. The reaction mixture was cooled, and the pH was adjusted to 2–3 with 1.0 M hydrochloric acid. Extraction was performed with ethyl acetate (3 × 20 mL). The organic layer was washed with brine (3 × 20 mL), dried over anhydrous sodium sulfate, and concentrated under reduced pressure to obtain the crude sample. Purification by silica gel column chromatography (petroleum ether:ethyl acetate = 7:1) yielded 473 mg of the target compound, with a yield of 87.1%. 1 H NMR (500MHz, CDCl3), δ: 8.84 (d, J = 2.0Hz, 1H), 8.23 ​​(d, J = 2.0Hz, 1H), 7.03 (d d,J=9.0,2.5Hz,1H),6.81-6.84(m,1H),6.62(dd,J=9.0,2.0Hz,1H),4.75(t ,J=6.5Hz,1H),4.57(m,1H),4.07-4.15(m,2H),3.76-3.86(m,2H),1.92-1.9 8(m,2H),1.87-1.90(m,4H),1.34-1.58(m,4H),0.92(t,J=7.0Hz,3H).HRMS:C 24 H 25 ClF3N2O5S[M+H] + Calculated value: 545.1125, Measured value: 545.1122.

[0265]

[0266] Example 16: Preparation of 2-(3-(3-chloro-5-(trifluoromethyl)pyridin-2-yl)-2-oxo-2,3-dihydrobenzothiazo-6-oxy)hexanoic acid-1-methoxy-1-oxopropyl-2-yl (IAd66)

[0267] (1) Preparation of 2-(3-(3-chloro-5-(trifluoromethyl)pyridin-2-yl)-2-oxo-2,3-dihydrobenzothiazol-6-oxy)hexanoic acid: 474 mg (1.0 mmol) of methyl 2-(3-(3-chloro-5-(trifluoromethyl)pyridin-2-yl)-2-oxo-2,3-dihydrobenzothiazol-6-oxy)hexanoate (IAdO2), 10.0 mL of tetrahydrofuran / water (2:1) solution and 80 mg (2.0 mmol) of NaOH were added to a 100 mL pear-shaped flask and stirred in an oil bath at 80 °C for 3.0 h. The reaction mixture was cooled, the pH was adjusted to 7.0 with 1.0 M hydrochloric acid, and extracted with ethyl acetate (3 × 20 mL). The organic layer was washed with brine (3 × 20 mL), dried over anhydrous sodium sulfate, and concentrated under reduced pressure to obtain the crude sample. The target compound was purified by silica gel column chromatography (petroleum ether: ethyl acetate = 2:1) to obtain 350 mg of the compound, with a yield of 76.2%. 1 HNMR (500MHz, CDCl3), δ: 8.84 (d, J = 2.0Hz, 1H), 8.23 ​​(d, J = 2.0Hz, 1H), 7.03 (dd, J = 9.0, 2.5Hz, 1H), 6.81-6.84 (m, 1H), 6.62(dd,J=9.0,2.0Hz,1H),4.54(t,J=7.0Hz,1H),1.92-1.98(m,2H),1.34-1.58(m,4H),0.92(t,J=7.0Hz,3H).HRMS:C 19 H 15 ClF3N2O4S[MH] - Calculated value: 459.0399, Measured value: 459.0394.

[0268]

[0269] (2) Preparation of 2-(3-(3-chloro-5-(trifluoromethyl)pyridin-2-yl)-2-oxo-2,3-dihydrobenzothiazol-6-oxy)hexanoic acid: 460 mg (1.0 mmol) of 2-(3-(3-chloro-5-(trifluoromethyl)pyridin-2-yl)-2-oxo-2,3-dihydrobenzothiazol-6-oxy)hexanoic acid and 5.0 mL of SOCl2 were added to a 100 mL pear-shaped flask and refluxed for 5.0 h. The reaction mixture was cooled, 10 mL of toluene was added, and the mixture was concentrated under reduced pressure to remove excess SOCl2, yielding 440 mg of the target compound (92.2%). No separation was required; the reaction proceeded directly to the next step.

[0270]

[0271] (3) Preparation of IAd66: In a 100 mL pear-shaped flask, 104 mg (1.0 mmol) of methyl lactate, 130 mg (1.3 mmol) of triethylamine, and 5.0 mL of dry dichloromethane were added. The mixture was cooled to 0 °C in an ice bath, and 574 mg (1.2 mmol) of a dichloromethane solution of 2-(3-(3-chloro-5-(trifluoromethyl)pyridin-2-yl)-2-oxo-2,3-dihydrobenzothiazol-6-oxy)hexanoyl chloride was slowly added dropwise with stirring. The temperature was kept below 0 °C. After the addition was complete, the mixture was stirred at room temperature for 3 h. The reaction solution was poured into 10 mL of ice water and extracted with dichloromethane (3 × 20 mL). The organic phases were combined, washed with saturated sodium carbonate aqueous solution, washed with water, dried over anhydrous sodium sulfate, and concentrated under reduced pressure to obtain the crude sample. The crude sample was purified by silica gel column chromatography (petroleum ether: ethyl acetate = 7:1) to obtain 498 mg of the target compound, with a yield of 91.3%. 1 H NMR(500MHz, CDCl3), δ:8.84(d,J=2.0Hz,1H),8.23(d,J=2.0Hz,1H),7.08(dd,J=9.0,2.5Hz,1H),6.80-6.86(m,1H),6.62(dd,J=9.0,2.0Hz,1H),5 .17(q,J=6.5Hz,1H),4.57(t,J=7.0Hz,1H),3.71(s,3H),1.92-1.98(m,2H ),1.51(d,J=6.5Hz,3H),1.34-1.58(m,4H),0.92(t,J=7.0Hz,3H).HRMS:C 23 H 23 ClF3N2O6S[M+H] + Calculated value: 547.0917, Measured value: 547.0920.

[0272]

[0273] Example 173: Preparation of 3-(3-chloro-5-(trifluoromethyl)pyridin-2-yl)-6-(1-oxo-1-(2-isopropylaminooxyethyl)hex-2-oxy)benzothiazol-2(3H)-one (IAd48)

[0274] 2-(3-(3-chloro-5-(trifluoromethyl)pyridin-2-yl)-2-oxo-2,3-dihydrobenzothiazol-6-oxy)hexanoyl chloride was prepared according to the method of Example 16.

[0275] In a 100 mL pear-shaped flask, 73 mg (1.0 mmol) of acetone oxime, 130 mg (1.3 mmol) of triethylamine, and 5.0 mL of dry dichloromethane were added. The mixture was cooled to 0 °C in an ice bath, and 574 mg (1.2 mmol) of a dichloromethane solution of 2-(3-(3-chloro-5-(trifluoromethyl)pyridin-2-yl)-2-oxo-2,3-dihydrobenzothiazol-6-oxy)hexanoyl chloride was slowly added dropwise with stirring, maintaining the temperature below 0 °C. After the addition was complete, the mixture was stirred at room temperature for 3 h. The reaction solution was poured into 10 mL of ice water and extracted with dichloromethane (3 × 20 mL). The organic phases were combined, washed with saturated sodium carbonate aqueous solution, washed with water, dried over anhydrous sodium sulfate, and concentrated under reduced pressure to obtain the crude sample. The crude sample was purified by silica gel column chromatography (petroleum ether:ethyl acetate = 7:1) to obtain 413 mg of the target compound, with a yield of 87.3%. 1 HNMR (500MHz, CDCl3), δ: 8.84 (d, J = 2.0Hz, 1H), 8.23 ​​(d, J = 2.0Hz, 1H), 7.08 (dd, J = 9.0, 2.5Hz, 1H), 6.80-6.86 (m, 1H), 6.62 (dd, J = 9 .0,2.0Hz,1H),4.57(t,J=7.0Hz,1H),2.04(s,3H),1.92-1.98(m,2H),1.91(s,3H),1.34-1.58(m,4H),0.92(t,J=7.0Hz,3H).HRMS:C 22 H 22 ClF3N3O4S[M+H] + Calculated value: 516.0972, Measured value: 516.0970.

[0276]

[0277] Example 18: Preparation of 2-(3-(3-chloro-5-(trifluoromethyl)pyridin-2-yl)-2-oxo-2,3-dihydrobenzothiazol-6-oxy)hexanoic acid propyne ester (IAd07)

[0278] 2-(3-(3-chloro-5-(trifluoromethyl)pyridin-2-yl)-2-oxo-2,3-dihydrobenzothiazol-6-oxy)hexanoic acid was prepared according to the method of Example 16.

[0279] In a 100 mL pear-shaped flask, 276 mg (2.0 mmol) of anhydrous K₂CO₃, 5.0 mL of dry DMF solution, and 460 mg (1.0 mmol) of 2-(3-(3-chloro-5-(trifluoromethyl)pyridin-2-yl)-2-oxo-2,3-dihydrobenzothiazol-6-oxy)hexanoic acid were added sequentially. The mixture was stirred in an oil bath at 60 °C for 30 min, followed by the addition of 142 mg (1.2 mmol) of bromopropyne. The mixture was stirred in an oil bath at 80 °C for 3 h. The reaction mixture was cooled, and the pH was adjusted to 2–3 with 1.0 M hydrochloric acid. Extraction was performed with ethyl acetate (3 × 20 mL). The organic layer was washed with brine (3 × 20 mL), dried over anhydrous sodium sulfate, and concentrated under reduced pressure to obtain the crude sample. Purification by silica gel column chromatography (petroleum ether:ethyl acetate = 5:1) yielded 295 mg of the target compound, with a yield of 75.4%. 1 H NMR (500MHz, CDCl3), δ: 8.84 (d, J = 2.0Hz, 1H), 8.23 ​​(d, J = 2.0Hz, 1H), 7.03 (dd, J = 6.0, 2.0Hz, 1H), 6.78-6.81 (m, 1H), 6.62 (dd, J = 9. 0,2.0Hz,1H),4.74(s,2H),4.57(t,J=7.0Hz,1H),3.28(s,1H),1.92-1.98(m,2H),1.34-1.58(m,4H),0.92(t,J=7.0Hz,3H).HRMS:C 22 H 19 ClF3N2O4S[M+H] + Calculated value: 499.0706, Measured value: 499.0710.

[0280]

[0281] Example 192: Preparation of 3-(3-(3-chloro-5-(trifluoromethyl)pyridin-2-yl)-2-oxo-2,3-dihydrobenzothiazol-6-oxy)-N-methyl-N-phenylhexanoamide (IAd72)

[0282] (1) Preparation of 2-chloro-N-methyl-N-phenyl-hexanoamide: In a 100 mL pear-shaped flask, 107 mg (1.0 mmol) of N-methylaniline, 130 mg (1.3 mmol) of triethylamine and 5.0 mL of dry dichloromethane were added. The mixture was cooled to 0 °C in an ice bath. 202 mg (1.2 mmol) of a dichloromethane solution of 2-chlorohexanoyl chloride was slowly added dropwise with stirring, keeping the temperature below 0 °C. After the addition was complete, the mixture was stirred at room temperature for 3 h. The reaction solution was poured into 10 mL of ice water and extracted with dichloromethane (3 × 20 mL). The organic phases were combined, washed with saturated sodium carbonate aqueous solution, washed with water, dried over anhydrous sodium sulfate, and concentrated under reduced pressure to obtain 227 mg of a pale yellow oily substance, with a yield of 95.3%.

[0283] No separation is needed; proceed directly to the next reaction.

[0284]

[0285] (2) Preparation of IAd72: 276 mg (2.0 mmol) of anhydrous K₂CO₃, 5.0 mL of dry DMF solution, and 346 mg (1.0 mmol) of 3-(3-chloro-5-(trifluoromethyl)pyridin-2-yl)-6-hydroxybenzothiazol-2(3H)-one (II-A) were added sequentially to a 100 mL pear-shaped flask. After stirring in an oil bath at 80 °C for 30 min, 287 mg (1.2 mmol) of 2-chloro-N-methyl-N-phenyl-hexamethyleneamide was added, and the mixture was stirred in an oil bath at 110 °C for 12 h. The reaction mixture was cooled, and the pH was adjusted to 2–3 with 1.0 M hydrochloric acid. Extraction was performed with ethyl acetate (3 × 20 mL). The organic layer was washed with brine (3 × 20 mL), dried over anhydrous sodium sulfate, and concentrated under reduced pressure to obtain the crude sample. Purification by silica gel column chromatography (petroleum ether: ethyl acetate = 7:1) yielded 415 mg of the target compound, with a yield of 84.2%. 1 HNMR(400MHz, CDCl3), δ:8.83(d,J=1.6Hz,1H),8.25(d,J=2.0Hz,1H),7.40-7.48(m,3H),7.23-7.25(m,2H),7.03(dd,J=6.0,2.0Hz,1H),6.78-6 .81(m,1H),6.62(dd,J=9.0,2.0Hz,1H),4.57(t,J=7.0Hz,1H),3.32(s,3H),1.92-1.98(m,2H),1.34-1.58(m,4H),0.92(t,J=7.0Hz,3H).HRMS:C 26 H 24 ClF3N3O3S[M+H] + Calculated value: 550.1179, Measured value: 550.1182.

[0286]

[0287] Scheme 1 of this invention provides a synthetic route for the 3,6-disubstituted benzothiazole compounds. Compounds V, IV, and II are important intermediates in the synthesis of these compounds. Examples 1-7 describe in detail the preparation methods of intermediates V, IV, and II to eliminate any obstacles to understanding the synthetic methods shown in Scheme 1. Examples 8-19 provide some methods for preparing 3,6-disubstituted benzothiazole compounds. Since these examples cannot exhaustively describe the synthetic methods of the 3,6-disubstituted benzothiazole compounds of general formula I or their salts, Examples 1-19 should not be considered as limitations on the 3,6-disubstituted benzothiazole compounds and their preparation methods. Those skilled in the art can use the technical insights from Examples 1-19, combined with conventional techniques, to obtain more 3,6-disubstituted benzothiazole compounds or their salts.

[0288] Composition Examples

[0289] Example 20 Herbicide Composition—Emulsifiable Concentrate

[0290] This embodiment prepares a herbicidal composition in the form of emulsifiable concentrate. The amount of each component added is a weight percentage, and the active compound (IAdO2) is added after being converted to a 100% weight percentage.

[0291] formula:

[0292]

[0293] Example 21 Herbicide Composition—Suspension Formulation

[0294] This embodiment prepares a herbicidal composition in the form of a suspension concentrate. The amount of each component added is a weight percentage, and the active compound (IAd72) is added after being converted to a 100% concentration.

[0295] formula:

[0296]

[0297] Example 22 Herbicide Composition—Dispersible Oil Suspension

[0298] This embodiment prepares a herbicidal composition in the form of a dispersible oil suspension. The amount of each component added is a weight percentage, and the active compound (IAd09) is added after being converted to a 100% weight percentage.

[0299] formula:

[0300]

[0301] Example 23 Herbicide Composition—Wettable Powder

[0302] This embodiment prepares a herbicidal composition in the form of a wettable powder. The amount of each component added is a weight percentage, and the active compound (IAd46) is added after being converted to a 100% weight percentage.

[0303] formula:

[0304]

[0305] The present invention does not impose any particular limitation on the formulation of the herbicidal composition, such as emulsifiable concentrates, suspension concentrates, dispersible oil suspensions, and wettable powders. For 3,6-disubstituted benzothiazole compounds or their salts with different structures, those skilled in the art can easily prepare formulations suitable for agricultural use and that exert the efficacy of 3,6-disubstituted benzothiazole compounds using conventional techniques; these will not be detailed here.

[0306] Bioactive Examples

[0307] Table 2 shows the Chinese names, Latin names, and initials of the tested plant (weed) varieties in the bioactivity examples.

[0308] Table 2. (Partial) list of tested weed varieties in the bioactivity examples.

[0309]

[0310]

[0311] The efficacy of the herbicidal agents in the herbicidal activity examples was investigated using the visual inspection method as described in NY / T 1155.3-2006 and NY / T1155.4-2006. The herbicidal activity of the agents was evaluated on a scale of 1 to 9 based on the symptoms and severity of damage to the tested weeds.

[0312] Level 1: All dead;

[0313] Level 2: Equivalent to 0-2.5% of the weeds in the blank control area;

[0314] Level 3: Equivalent to 2.6-5% of the weeds in the blank control area;

[0315] Level 4: Equivalent to 5.1-10% of the weeds in the blank control area;

[0316] Level 5: Equivalent to 10.1-15% of the weeds in the blank control area;

[0317] Level 6: Equivalent to 15.1-25% of the weeds in the blank control area;

[0318] Level 7: Equivalent to 25.1-35% of the weeds in the blank control area;

[0319] Level 8: Equivalent to 35.1%–67.5% of the weeds in the blank control area;

[0320] Level 9: Equivalent to 67.6%–100% of the weeds in the blank control area.

[0321] Example 24 Pre-emergence herbicidal activity test

[0322] The pre-emergence herbicidal activity of some 3,6-disubstituted benzothiazole compounds was evaluated according to the method in NY / T 1155.3-2006. Each tested 3,6-disubstituted benzothiazole compound was prepared into a 10% emulsifiable concentrate according to the formulation shown in Example 20. Soil spraying was performed one day after weed sowing, and the herbicidal effect was investigated 21 days after treatment. The results are shown in Table 3.

[0323] As shown in Table 3, at application rates of 15–45 g / ha, the tested 3,6-disubstituted benzothiazole compounds all exhibited good pre-emergence weed control effects against amaranth, velvetleaf, lambsquarters, purslane, speedwell, geranium, barnyard grass, and foxtail.

[0324] Table 3 shows the pre-emergence herbicidal effects of some 3,6-disubstituted benzothiazole compounds.

[0325]

[0326]

[0327] Example 25 Post-emergence herbicidal activity test

[0328] The post-emergence herbicidal activity of some 3,6-disubstituted benzothiazole compounds was evaluated according to the method in NY / T 1155.4-2006. Each tested 3,6-disubstituted benzothiazole compound was prepared into a 10% emulsifiable concentrate according to the formulation shown in Example 20. Sprays were applied to grass weeds at the 2-3 leaf stage and broadleaf weeds at the 3-4 leaf stage. Results were collected 21 days after treatment and are shown in Table 4.

[0329] As shown in Table 4, at application rates of 15–45 g / ha, the tested 3,6-disubstituted benzothiazole compounds all exhibited good post-emergence weed control effects against amaranth, velvetleaf, lambsquarters, purslane, speedwell, geranium, barnyard grass, and foxtail.

[0330] Table 4 shows the post-emergence herbicidal effects of some 3,6-disubstituted benzothiazole compounds.

[0331]

[0332]

[0333]

[0334] Example 26 Crop Safety Evaluation Experiment

[0335] The phytotoxicity evaluation of the tested 3,6-disubstituted benzothiazole compounds was conducted according to the methods in NY / T 1965.2-2010. The evaluation was based on the growth inhibition rate of the tested crops, with the specific indicators being:

[0336] Safe and without phytotoxicity: inhibition rate is 0.

[0337] Mild phytotoxicity: inhibition rate 1%–10%;

[0338] Moderate phytotoxicity: inhibition rate 11%–30%;

[0339] Severe phytotoxicity: Inhibition rate 31%–50%;

[0340] Severe phytotoxicity: Inhibition rate > 50%.

[0341] Winter wheat, rice, and maize were used as test crops, and crop safety was evaluated according to the method in NY / T 1965.2-2010. The tested 3,6-disubstituted benzothiazole compounds were prepared into a 10% emulsifiable concentrate (containing 3% methyl parathion) according to the formulation shown in Example 20, and applied at three dosages: 45 g / ha, 90 g / ha, and 135 g / ha. The results of the crop safety evaluation are shown in Table 5.

[0342] Table 5. Crop safety evaluation results of the compounds on winter wheat, rice, and maize.

[0343]

[0344]

[0345] Table 5 shows that at application rates of 45 g / ha and 90 g / ha, compounds IAd02, ICa02, and IAd72 had no effect on the growth of winter wheat, rice, and maize. Only at an application rate of 135 g / ha did compound IAd02 show slight inhibition on winter wheat and maize, compound ICa02 show slight inhibition on winter wheat, and compound IAd72 show slight inhibition on winter wheat after soil treatment. Therefore, the tested 3,6-disubstituted benzothiazole compounds exhibit excellent crop safety for common field crops such as winter wheat, rice, and maize.

Claims

1. A benzothiazole compound having a chemical structure as shown in formula (I), ###0001### Formula (I) （I） In formula (I), X is a leaving group. R 1 CF3; R 2 is CI, F, H; R 3 selected from C 1~ C8alkyl; R 4 selected from 2. A salt of the benzothiazole compound of claim 1.

3. A method for synthesizing the benzothiazole compound of claim 1, which route is: ###0002### Route 1 ###0003### Route 2 ###0004### Route 3 ###0005### Route 4 ###0006### Route 5 ###0007### Route 6 ###0008### Route 7 ###0009### Route 8 ###0010### Route 9 ###0011### Route 10 ###0012### Route 11 ###0013### Route 12 ###0014### Route 13 ###0015### Route 14 ###0016### Route 15 ###0017### Route 16 ###0018### Route 17 ###0019### Route 18 ###0020### Route 19 ###0021### Route 20 ###0022### Route 21 ###0023### Route 22 ###0024### Route 23 ###0025### Route 24 ###0026### Route 25 ###0027### Route 26 ###0028### Route 27 ###0029### Route 28 ###0030### Route 29 ###0031### Route 30 ###0032### Route 31 ###0033### Route 32 ###0034### Route 33 ###0035### Route 34 ###0036### Route 35 ###0037### Route 36 ###0038### Route 37 ###0039### Route 38 ###0040### Route 39 ###0041### Route 40 ###0042### Route 41 ###0043### Route 42 ； ​ 4. The method of synthesis of claim 3, wherein, ​ 5. The use of the benzothiazole compounds as claimed in claim 1 in agriculture, characterized in that, ​ ​

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