A 4-methylsulfonylbenzamide compound, preparation method, herbicidal composition and use thereof

Abstract

The present invention relates to a 4-methylsulfonylbenzamide compound having a sulfur-containing substituent at the 3-position of a general formula (I), a stereoisomer thereof, an agriculturally acceptable salt thereof, a preparation method thereof, a herbicidal composition and use thereof in the field of plant protection, wherein R1, R2, X, Q and n are as defined herein.

Description

Technical Field

[0001] The invention belongs to the field of pesticide herbicides, and specifically relates to a 4-methylsulfonylbenzamide compound, a preparation method, a herbicidal composition and use. Background Art

[0002] Chemical weed control using herbicides is the most economical and effective means of weed control. However, long-term continuous high-dose use of a single variety or a single mode of action of chemical herbicides is likely to cause problems such as weed resistance and resistance evolution, and the development of new varieties of pesticides is the core means to solve the above problems. Patents WO2014086746A1, WO2016146561A1, WO2014086734A1, WO2013017559A1, WO2017144402A1, WO2012126932A1, WO2013087577A1, WO2012028579A1, and WO2011035874A1 record certain aromatic formamide compounds and their use as herbicides. However, the currently known aromatic formamide compounds are still not ideal in terms of herbicidal activity, crop safety, and resistant weed management. Therefore, there is an urgent need in the market for new herbicides that not only have good herbicidal activity and are crop safe, but can also effectively prevent and control resistant weeds. Summary of the invention

[0003] The technical problem to be solved by the present invention is to provide a novel 4-methylsulfonylbenzamide compound, a preparation method, a herbicidal composition and use thereof, wherein the compound has excellent herbicidal activity, high crop safety and weed resistance management capability.

[0004] The technical solution of the present invention to solve the above technical problems is as follows:

[0005] The present invention provides a 4-methylsulfonylbenzamide compound represented by the general formula (I), a stereoisomer thereof or an agriculturally acceptable salt thereof:

[0006]

[0007] in:

[0008] Q stands for Q1, Q2, Q3, or Q4, as shown below:

[0009]

[0010] X represents fluorine, chlorine, bromine, CN, mesyl or nitro;

[0011] R1 represents C 3～6 Alkyl, C 3～6 Cycloalkyl, C 3～6 Cycloalkyl-C1～6 Alkyl, aromatic ring substituted C 1～6 Alkyl, substituted aromatic ring substituted C 1～6 Alkyl, halogenated C 1～6 Alkyl, C 2～6 Alkenyl, C 2～6 Alkynyl, NC-C 1～6 Alkyl, halo-C 2～6 Alkenyl, C 2～6 Alkyl-OC 1～6 Alkyl, halogenated C 1～6 Alkyl-OC 1～6 alkyl;

[0012] R2 represents hydrogen, C 1～6 Alkyl, halogenated C 1～6 Alkyl, C 3～6 Cycloalkyl, C 2～6 Alkenyl, halo-C 2～6 Alkenyl, C 2～6 Alkynyl, halo-C 3～6 Alkynyl, C 3～6 Cycloalkyl, halo-C 3～6 Cycloalkyl, C 3～6 Cycloalkyl-C 1～6 Alkyl, halo-C 3～6 Cycloalkyl-C 1～6 Alkyl, Ra(O)CC 1～6 Alkyl, RaO(O)CC 1～6 Alkyl, (Ra)2N(O)CC 1～6 Alkyl, NC-C 1～6 Alkyl, RaO-C 1～6 Alkyl, Ra(O)CO-C 1～6 Alkyl, Rb(O)2SO-C 1～6 Alkyl, (Ra)2N-C 1～6 Alkyl, Ra(O)C(Ra)NC 1～6 Alkyl, Rb(O)2S(Ra)NC 1～6 Alkyl, Rb(O)nS-C 1～6 Alkyl, RaO(O)2S-C 1～6 Alkyl, (Ra)2N(O)2S-C 1～6 alkyl, Ra(O)C, RaO(O)C, (Ra)2N(O)C, RaO, (Ra)2N, RbO(O)C(Ra)N, (Ra)2N(O)C(Ra)N, Rb(O)2S or benzyl substituted with 1, 2 or 3 groups selected from methyl, ethyl, methoxy, nitro, trifluoromethyl and halogen;

[0013] Rx represents hydrogen, C 1～6 Alkyl, halo-C1～6 Alkyl, C 2～6 Alkenyl, halo-C 2～6 Alkenyl, C 2～6 Alkynyl or halo-C 3～6 Alkynyl, wherein the above 6 groups are substituted by 0, 1, 2 or 3 groups selected from the following: nitro, cyano, (Rf)3Si, (ReO)2(O)P, Re(O)nS, (Ra)2N, RaO, Ra(O)C, RaO(O)C, Ra(O)CO, RbO(O)CO, Ra(O)C(Ra)N, Rb(O)2S(Ra)N, C 3～6 Cycloalkyl, heteroaryl, heterocyclyl and phenyl, wherein the cycloalkyl, heteroaryl, heterocyclyl and phenyl are substituted by 1, 2 or 3 groups selected from the following: 1～6 Alkyl, halo-C 1～6 Alkyl, C 1～6 Alkoxy, halo-C 1～6 Alkoxy and halogen, wherein the heterocyclic group carries n oxo groups;

[0014] or Rx represents C 3～7 Cycloalkyl, heteroaryl, heterocyclic or phenyl, wherein the above four groups are substituted by 0, 1, 2 or 3 groups selected from the following: halogen, nitro, cyano, C 1～6 Alkyl, halo-C 1～6 Alkyl, C 3～6 Cycloalkyl, C 1～6 Alkyl-S(O)n, C 1～6 Alkoxy, halo-C 1～6 Alkoxy and C 1～6 Alkoxy-C 1～4 alkyl;

[0015] Ry represents hydrogen, C 1～6 Alkyl, halo-C 1～6 Alkyl, C 2～6 Alkenyl, halogenated C 2～6 Alkenyl, C 2～6 -Alkynyl, halo-C 3～6 Alkynyl, C 3～6 Cycloalkyl, C 1～6 Alkoxy, halo-C 1～6 Alkoxy, C 2～6 Alkenyloxy, C 2～6alkynyloxy, cyano, nitro, methylthio, methylsulfinyl, methylsulfonyl, acetylamino, benzoylamino, methoxycarbonyl, ethoxycarbonyl, methoxycarbonylmethyl, ethoxycarbonylmethyl, benzoyl, methylcarbonyl, piperidinylcarbonyl, trifluoromethylcarbonyl, halogen, amino, aminocarbonyl, methylaminocarbonyl, dimethylaminocarbonyl, methoxymethyl, or represents heteroaryl, heterocyclic or phenyl, each of which is substituted by 1, 2 or 3 groups selected from the following: C 1～6 Alkyl, halo-C 1～6 Alkyl, C 1～6 Alkoxy, halo-C 1～6 Alkoxy and halogen, wherein the heterocyclic group carries n oxo groups;

[0016] Rz represents hydrogen, C 1～6 Alkyl, RaO-C 1～6 Alkyl, RgCH2, C 3～7 Cycloalkyl, halo-C 1～6 Alkyl, C 2～6 Alkenyl, halo-C 2～6 Alkenyl, C 2～6 Alkynyl, halo-C 3～6 alkynyl, RaO, Ra(H)N, methoxycarbonyl, ethoxycarbonyl, methylcarbonyl, dimethylamino, trifluoromethylcarbonyl, acetylamino, methylthio, methylsulfinyl, methylsulfonyl, or represents heteroaryl, heterocyclic, benzyl or phenyl, each of which is substituted by 1, 2 or 3 groups selected from the group consisting of halogen, nitro, cyano, C 1～6 Alkyl, halo-C 1～6 Alkyl, C 3～6 Cycloalkyl, C 1～6 Alkyl-S(O) n , C 1～6 Alkoxy, halo-C 1～6 Alkoxy and C 1～6 Alkoxy-C 1～4 Alkyl, wherein the heterocyclic group carries n oxo groups;

[0017] Ra represents hydrogen, C 1～6 Alkyl, halo-C 1～6 Alkyl, C 2～6 Alkenyl, halo-C 2～6 Alkenyl, C 2～6 Alkynyl, halo-C 3～6 Alkynyl, C 3～6 Cycloalkyl, C 3～6 Cycloalkenyl, halo-C 3～6 Cycloalkyl, C 3～6 Cycloalkyl-C 1～6 Alkyl, C 1～6 Alkyl-OC 1～6Alkyl, cycloalkyl-C 1～6 Alkyl-OC 1～6 Alkyl, Phenyl, Phenyl-C 1～6 Alkyl, Heteroaryl, Heteroaryl-C 1～6 Alkyl, heterocyclyl, heterocyclyl-C 1～6 Alkyl, phenyl-OC 1～6 Alkyl, Heteroaryl-OC 1～6 Alkyl, heterocyclic-OC 1～6 Alkyl, phenyl-N(Rc)-C 1～6 -alkyl, heteroaryl-N(Rc)-C 1～6 Alkyl, Heterocyclyl-N(Rc)-C 1～6 Alkyl, Phenyl-S(O)nC 1～6 Alkyl, Heteroaryl-S(O)nC 1～6 Alkyl or heterocyclic-S(O)nC 1～6 Alkyl, wherein the last fifteen radicals mentioned are in each case substituted by s radicals selected from the group consisting of nitro, halogen, cyano, thiocyano, C 1～6 Alkyl, halo-C 1～6 Alkyl, C 3～6 Cycloalkyl, RcO(O)C, (Rc)2N(O)C, RcO, (Rc)2N, Rd(O)nS, RcO(O)2S, (Rc)2N(O)2S and RcO-C 1～6 Alkyl, wherein the heterocyclic group has n oxo groups;

[0018] Rb stands for C 1～6 Alkyl, halo-C 1～6 Alkyl, C 2～6 Alkenyl, halo-C 2～6 Alkenyl, C 2～6 Alkynyl, halo-C 3～6 Alkynyl, C 3～6 Cycloalkyl, C 3～6 Cycloalkenyl, halo-C 3～6 Cycloalkyl, C 3～6 Cycloalkyl-C 1～6 Alkyl, C 1～6 Alkyl-OC 1～6 Alkyl, cycloalkyl-C 1～6 Alkyl-OC 1～6 Alkyl, Phenyl, Phenyl-C 1～6 Alkyl, Heteroaryl, Heteroaryl-C 1～6 Alkyl, heterocyclyl, heterocyclyl-C 1～6 Alkyl, phenyl-OC 1～6 -alkyl, heteroaryl-OC 1～6 Alkyl, heterocyclic-OC 1～6 Alkyl, phenyl-N(Rc)-C1～6 Alkyl, Heteroaryl-N(Rc)-C 1～6 Alkyl, Heterocyclyl-N(Rc)-C 1～6 Alkyl, Phenyl-S(O)nC 1～6 Alkyl, Heteroaryl-S(O)nC 1～6 Alkyl or heterocyclic-S(O)nC 1～6 Alkyl, wherein the last fifteen radicals mentioned are in each case substituted by 1, 2 or 3 radicals selected from the group consisting of nitro, halogen, cyano, thiocyano, C 1～6 Alkyl, halo-C 1～6 Alkyl, C 3～6 Cycloalkyl, RcO(O)C, (Rc)2N(O)C, RcO, (Rc)2N, Rd(O)nS, RcO(O)2S, (Rc)2N(O)2S and RcO-C 1～6 Alkyl, wherein the heterocyclic group has n oxo groups;

[0019] Rc represents hydrogen, C 1～6 Alkyl, halo-C 1～6 Alkyl, C 2～6 Alkenyl, C 2～6 Alkynyl, C 3～6 Cycloalkyl, C 3～6 Cycloalkyl-C 1～6 Alkyl or phenyl;

[0020] Rd stands for C 1～6 Alkyl, halo-C 1～6 Alkyl, C 2～6 Alkenyl, C 2～6 Alkynyl, C 3～6 Cycloalkyl, C 3～6 Cycloalkyl-C 1～6 Alkyl or phenyl;

[0021] Re represents hydrogen or C 1～4 alkyl;

[0022] Rf stands for C 1～4 alkyl;

[0023] Rg represents acetoxy, acetamido, N-methylacetamido, benzoyloxy, benzamido, N-methylbenzamido, methoxycarbonyl, ethoxycarbonyl, benzoyl, methylcarbonyl, piperidinylcarbonyl, morpholinylcarbonyl, trifluoromethylcarbonyl, aminocarbonyl, methylaminocarbonyl, dimethylaminocarbonyl, C 3～6 Cycloalkyl, or represents heteroaryl or heterocyclyl, which is substituted in each case by s radicals selected from the group consisting of methyl, ethyl, methoxy, trifluoromethyl and halogen;

[0024] n represents 0, 1 or 2;

[0025] When n represents 1, the sulfur atom connected thereto may be selected from R type or S type, or a mixture of the two, wherein the ratio of R to S in the mixture is 1:99 to 99:1;

[0026] s represents 0, 1, 2, or 3;

[0027] In some preferred technical solutions, the 4-methylsulfonylbenzamide compound, its stereoisomer or its agriculturally acceptable salt:

[0028]

[0029] in:

[0030] Q stands for Q1, Q2, Q3, or Q4, as shown below:

[0031]

[0032] X stands for chlorine;

[0033] R1 represents C 3～6 Alkyl, C 3～6 Cycloalkyl, halogenated C 3～6 Cycloalkyl, C 3～6 Cycloalkylmethyl, aromatic ring substituted methyl, halogenated C 3～4 Alkyl, C 2～4 Alkenyl, C 2～4 Alkynyl, NC-C 1～4 Alkyl, halo-C 2～4 Alkenyl, C 1～2 Alkyl-OC 1～2 Alkyl or halogenated C 1～2 Alkyl-OC 1～2 alkyl;

[0034] R2 represents hydrogen, C 1～3 Alkyl, halogenated C 1～3 Alkyl, cyclopropyl, halogenated cyclopropyl, C 2～3 Alkenyl, halo-C 2～3 Alkenyl, C 2～3 Alkynyl or halo C 2～3 Alkynyl, C 1～6 Alkyl-OC 1～6 alkyl;

[0035] Rx represents hydrogen, C 1～3 Alkyl, halo-C 1～3 Alkyl, C 2～3 Alkenyl, halo-C 2～3 Alkenyl, C 2～3 Alkynyl, halo C 2～3 Alkynyl, cyclopropyl or halocyclopropyl;

[0036] Ry represents hydrogen, C 1～3 Alkyl, halo-C 1～3 Alkyl, C 2～3 Alkenyl, halo-C 2～3 Alkenyl, C 2～3 Alkynyl, halo C 2～3 Alkynyl, cyclopropyl or halocyclopropyl;

[0037] Rz represents hydrogen, C 1～3 Alkyl, halo-C 1～3 Alkyl, C 2～3 Alkenyl, halo-C 2～3 Alkenyl, C 2～3 Alkynyl, halo C 2～3 Alkynyl, cyclopropyl or halocyclopropyl;

[0038] n represents 0, 1 or 2;

[0039] When n represents 1, the sulfur atom connected thereto can be selected from R type or S type, or a mixture of the two, and the ratio of R to S in the mixture is 1:99 to 99:1. In some preferred technical solutions, the 4-methylsulfonylbenzamide compound, its stereoisomer or its agriculturally acceptable salt is:

[0040]

[0041] in:

[0042] Q stands for Q1, Q2, Q3, or Q4, as shown below:

[0043]

[0044] X stands for chlorine;

[0045] R1 represents CH2CH2CH3, CH(CH3)2, CH2CH2CH2CH3, CH(CH3)CH2CH3, cyclopropylmethyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, CH2CF3, CH2CH=CH2, CH2CH2Cl, CH2CH(CH3)2, C(CH3)3, CH2CH2CH2CH2CH3, CH(CH3)CH2CH2CH3, CH2CH2CH(CH3)2, C(CH3)2CH2CH3, CH2CH(CH3)CH2CH3, CH2C6H5, CH(CH3)C6H5, CH2CF2H, CH2CFH2, CH(CH3)CH=CH2, (E)-CH2CH=CHCH3, (Z)-CH2CH=CHCH3 , CH2CH=C(CH3)2, propargyl, but-3-en-2-yl, but-2-en-1-yl, CF2CF3, CF2CF2CF3, CH2CF2CF3, CH2CH2CF3, CH2CH2CF2H, CH2CH2CFH2, CH2CN, CH2CH2CN, CH(CH3)CN, CH(CH3)CH2CN, CHClCH3, (E)-CH2CH=CHCl, (Z)-CH2CH=CHCl, CH2CH=CCl2, (E)-CH2CH=CHOCH3, (Z)-CH2CH=CHOCH3, CH2CH2OCF3, CH2CH2OCF2H, CH2CH2OCFH2, CH2OCH3, CH2CF2H, CH2CFH2;

[0046] R2 represents hydrogen, methyl, ethyl, CH(CH3)2, C 1～6 Alkyl OC 1～6 alkyl;

[0047] Rx represents hydrogen, methyl, ethyl;

[0048] Ry represents: hydrogen, methyl, ethyl, isopropyl, cyclopropyl, CH2CH2CH3, CN

[0049] Rz represents hydrogen, methyl, ethyl, isopropyl, cyclopropyl, CH2CH2CH3, CH2CH2CH3, CF3, cyclobutyl, furan-2-yl, C6H5, 4-fluorophenyl, CH3CH2OCO;

[0050] n represents 0, 1 or 2;

[0051] When n represents 1, the sulfur atom connected thereto can be selected from R type or S type, or a mixture of the two, and the ratio of R to S in the mixture is 1:99 to 99:1.

[0052] In some more preferred technical solutions, the 4-methylsulfonylbenzamide compound, its stereoisomer or its agriculturally acceptable salt is selected from Table 1.

[0053] Table 1

[0054]

[0055]

[0056]

[0057]

[0058]

[0059]

[0060]

[0061]

[0062]

[0063]

[0064]

[0065]

[0066]

[0067]

[0068]

[0069]

[0070]

[0071]

[0072]

[0073]

[0074]

[0075]

[0076]

[0077]

[0078]

[0079]

[0080]

[0081]

[0082]

[0083]

[0084]

[0085]

[0086]

[0087]

[0088]

[0089]

[0090] The present invention also provides a first method for preparing the 4-methylsulfonylbenzamide compounds, their stereoisomers or their agriculturally acceptable salts, characterized in that it comprises the following steps:

[0091] (1) The compound represented by the general formula (VI) undergoes a substitution reaction with a differently substituted thiol or thiolate to generate a compound represented by the general formula (V);

[0092] (2) the compound represented by the general formula (V) undergoes a condensation reaction with the compound represented by the general formula (IV) to generate a compound represented by the general formula (III);

[0093] (3) The compound represented by the general formula (III) is subjected to an oxidation reaction to prepare the compound represented by the general formula (II);

[0094] (4) The compound represented by the general formula (II) is subjected to a substitution reaction to obtain a 4-methylsulfonylbenzamide compound represented by the general formula (I);

[0095]

[0096] in:

[0097] X1 is selected from fluorine or chlorine;

[0098] R1, R2, X and Q are as described above, and n represents 1 or 2.

[0099] The present invention also provides a second method for preparing the 4-methylsulfonylbenzamide compounds, their stereoisomers or their agriculturally acceptable salts, which is characterized by comprising the following steps:

[0100] (1) the compound represented by the general formula (VI) undergoes a substitution reaction with a hydrogen sulfide to generate a thiophenol compound represented by the general formula (VII);

[0101] (2) the compound represented by the general formula (VII) undergoes a substitution reaction with the compound represented by the general formula (VIII) to generate a compound represented by the general formula (V);

[0102] (3) the compound represented by the general formula (V) undergoes a condensation reaction with the compound represented by the general formula (IV) to generate a compound represented by the general formula (III);

[0103] (4) The compound represented by the general formula (III) is subjected to an oxidation reaction to prepare the compound represented by the general formula (II);

[0104] (5) The compound represented by the general formula (II) is subjected to a substitution reaction to obtain a 4-methylsulfonylbenzamide compound represented by the general formula (I);

[0105]

[0106] in:

[0107] X1 is selected from fluorine or chlorine;

[0108] X2 is selected from chlorine, bromine, iodine, MsO (methylsulfonyloxy), TfO (trifluoromethylsulfonyloxy) or TsO (p-toluenesulfonyloxy);

[0109] R1, R2, X and Q are as described above.

[0110] The present invention also provides a herbicidal composition, characterized in that it comprises the 4-methylsulfonylbenzamide compound, its stereoisomer or its agriculturally acceptable salt; preferably, it also comprises one or more additional herbicides and / or safeners; more preferably, it also comprises an agrochemically acceptable formulation adjuvant.

[0111] The present invention also provides a method for controlling weeds, characterized in that it comprises applying a herbicidally effective amount of the 4-methylsulfonylbenzamide compound, its stereoisomer or its agriculturally acceptable salt or the herbicidal composition to plants or weedy areas.

[0112] The present invention also provides the use of the 4-methylsulfonylbenzamide compound, its stereoisomer or its agriculturally acceptable salt or the herbicidal composition for preventing and controlling weeds.

[0113] The present invention also provides the use of the 4-methylsulfonylbenzamide compound, its stereoisomer or its agriculturally acceptable salt or the herbicidal composition in controlling weeds.

[0114] The present invention also provides the 4-methylsulfonylbenzamide compound, its stereoisomer or its agriculturally acceptable salt or the herbicidal composition for controlling weeds in useful crops, wherein the useful crops are transgenic crops or crops treated with genome editing technology.

[0115] The compounds of the general formula (I) (and / or their salts) of the present invention - hereinafter collectively referred to as "compounds of the present invention" - have excellent herbicidal efficacy against a wide spectrum of economically important monocotyledonous and dicotyledonous annual harmful plants.

[0116] The present invention therefore also provides a method for controlling unwanted plants or regulating plant growth, preferably in plant crops, wherein one or more compounds according to the invention are applied to plants (e.g. harmful plants, such as monocotyledonous or dicotyledonous weeds or unwanted crop plants), seeds (e.g. grains, seeds or asexual propagation bodies such as tubers or shoot parts with buds) or areas where plants grow (e.g. cultivation areas). The compounds according to the invention can be applied, for example, before sowing (if appropriate, also by incorporation into the soil), before emergence or after emergence. Some representative specific examples of the monocotyledonous and dicotyledonous weed flora that can be controlled by the compounds according to the invention are as follows, but the enumeration is not intended to be a restriction to specific genera and species.

[0117] Monocotyledonous harmful plants of the following genera: Aegilops, Agropyron, Agrostis, Alopecurus, Apera, Avena, Brachiaria, Bromus, Cenchrus, Commelina, Cynodon, Cyperus, Dactyloctenium, Digitaria, Echinochloa, Eleocharis, Eleusine, Eragrosti s), Eriochloa, Festuca, Fimbristylis, Heteranthera, Imperata, Ischaemum, Leptochloa, Lolium, Monochoria, Panicum, Paspalum, Phalaris, Phleum, Poa, Rottboellia, Sagittaria, Scirpus, Setaria, and Sorghum.

[0118] Dicotyledonous weeds of the following genera: Abutilon, Amaranthus, Ambrosia, Anoda, Anthemis, Aphanes, Artemisia, Atriplex, Bellis, Bidens, Capsella, Carduus, Cassia, Centaurea, Chenopodium, Thistle Cirsium, Convolvulus, Datura, Desmodium, Emex, Erysimum, Euphorbia, Galeopsis, Galinsoga, Galium, Hibiscus, Ipomoea, Kochia, Lamium, Lepidium, Linderni a), Matricaria, Mentha, Mercurialis, Mullugo, Myosotis, Papaver, Pharbitis, Plantago, Polygonum, Portulaca, Ranunculus, Raphanus, Rorippa, Rotala, Rumex, Salsola, Senecio, Sesbania, Sida, Sinapis, Solanum, Sonchus, Sphenoclea, Stellaria, Taraxacum, Thlaspi, Trifolium, Urtica, Veronica, Viola, Xanthium.

[0119] If the compounds of the invention are applied to the soil surface before germination, the emergence of weed seedlings is completely prevented, or the weeds grow until they reach the cotyledon stage but then cease to grow.

[0120] If the active ingredients are applied to the green parts of the plants after emergence, growth stops after the treatment and the harmful plants remain at the growth stage at the time of application, or they die completely after a certain period of time, thus eliminating competition from weeds that are harmful to the crop plants at a very early stage and in a permanent manner.

[0121] The compounds according to the invention can be selective in crops of useful plants and can also be used as nonselective herbicides.

[0122] Due to their weeding and plant growth regulating properties, the active ingredients can also be used to control harmful plants in crops of known or undeveloped genetically modified plants. Usually, transgenic plants are characterized by particularly favorable properties, such as resistance to certain active ingredients used in the agricultural industry, particularly resistance to certain herbicides, resistance to plant diseases or pathogens of plant diseases (such as certain insects or microorganisms, such as fungi, bacteria or viruses). Other specific features relate to, for example, the yield, quality, storage, composition and specific ingredients of the harvested material. For example, there are known transgenic plants with high starch content or altered starch quality, or those transgenic plants with different fatty acid compositions in the harvested material. Other specific properties are tolerance or resistance to abiotic stress factors such as heat, cold, drought, salinity and ultraviolet radiation.

[0123] Preference is given to using the compounds of the formula (I) according to the invention or their salts in transgenic crops of economically important useful and ornamental plants.

[0124] The compounds of the general formula (I) can be employed as herbicides in crops of useful plants which are resistant or have been made resistant by genetic engineering to the phytotoxic effects of the herbicides.

[0125] The conventional methods of producing novel plants with altered properties compared to existing plants include, for example, conventional breeding methods and the generation of mutants. Alternatively, novel plants with altered properties can be produced with the aid of recombinant methods (see, for example, EP 0221044, EP 0131624). For example, the following have been described: genetic modification of crop plants in order to alter the starch synthesized in the plants (e.g. WO 92 / 011376 A, WO 92 / 014827 A, WO 91 / 019806 A); transgenic crop plants which are resistant to certain herbicides of the glufosinate class (see, e.g. EP 0242236 A, EP 0242246 A) or glyphosate class (WO 92 / 000377 A) or sulfonylurea class (EP 0257993 A, US 5,013,659) or combinations or mixtures of these herbicides by "gene stacking", e.g. transgenic crop plants such as corn or soybeans with the trade name or the name Optimum™ GAT™ (glyphosate tolerant ALS),

[0126] - transgenic crop plants, such as cotton, which produce Bacillus thuringiensis toxins (Bt toxins) and thus render them resistant to specific pests (EP 0142924 A, EP 0193259 A),

[0127] - transgenic crop plants with altered fatty acid composition (WO 91 / 013972 A),

[0128] - genetically modified crop plants with new components or secondary metabolites (e.g. new phytoalexins) which lead to enhanced disease resistance (EP 0309862 A, EP 0464461 A),

[0129] - Genetically modified plants with reduced photorespiration, which have higher yield and higher stress tolerance (EP0305398A),

[0130] - transgenic crop plants producing pharmaceutically or diagnostically important proteins ("molecular pharming"),

[0131] - transgenic crop plants characterized by higher yield or better quality,

[0132] - Transgenic crop plants, which are characterized by a combination of novel traits, for example, as mentioned above ("gene stacking").

[0133] Many molecular biology techniques which can be used to generate novel transgenic plants with improved properties are known in principle; see, for example, I. Potrykus and G. Spangenberg (eds.), Gene Transfer to Plants, Springer Lab Manual (1995), Springer Verlag Berlin, Heidelberg or Christou, "Trends in Plant Science" 1 (1996) 423-431.

[0134] For this genetic manipulation, a nucleic acid molecule that can be mutated or sequence-changed by a recombinant DNA sequence can be introduced into a plasmid. For example, base swaps, removal of partial sequences, or addition of natural or synthetic sequences can be performed by standard methods. In order to connect DNA fragments to each other, adapters or linkers can be placed on the fragments; see, for example, Sambrook et al., 1989, Molecular Cloning, A Laboratory Manual, 2nd edition, Cold Spring Harbor Laboratory Press, Cold Spring Harbor, NY; or Winnacker "Gene und Klone", VCH Weinheim, 2nd edition, 1996.

[0135] For example, the production of plant cells with reduced gene product activity can be achieved by expressing at least one corresponding antisense RNA, a sense RNA for achieving co-inhibition, or expressing at least one appropriately constructed ribozyme that specifically cuts the transcript of the above-mentioned gene product. For this reason, DNA molecules comprising the complete coding sequence of the gene product (including any flanking sequences that may exist) can first be used, as well as DNA molecules comprising only a portion of the coding sequence, in which case these portion coding sequences must be long enough to have an antisense effect in the cell. DNA sequences that have a high degree of homology to the coding sequence of the gene product but are not identical thereto can also be used.

[0136] When expressing nucleic acid molecules in plants, the synthesized protein can be located in any desired compartment of the plant cell. However, in order to achieve localization in a specific compartment, for example, the coding region can be connected to a DNA sequence that ensures localization in a specific compartment. Such sequences are known to those skilled in the art (see, for example, Braun et al., EMBO J. 11 (1992), 3219-3227; Wolter et al., Proc. Natl. Acad. Sci. USA 85 (1988), 846-850; Sonnewald et al., Plant J. 1 (1991), 95-106). Nucleic acid molecules can also be expressed in organelles of plant cells.

[0137] Transgenic plant cells can be regenerated by known techniques to give rise to whole plants. In principle, transgenic plants can be plants of any desired plant variety, i.e. not only monocots but also dicots. Thus, transgenic plants with altered properties can be obtained by overexpression, suppression or inhibition of homologous (=natural) genes or gene sequences, or expression of heterologous (=foreign) genes or gene sequences.

[0138] The compounds (I) according to the invention can preferably be used in transgenic crops which are resistant to growth regulators such as 2,4-D, dicamba, or to herbicides which inhibit essential plant enzymes such as acetolactate synthase (ALS), EPSP synthase, glutamine synthase (GS) or hydroxyphenylpyruvate dioxygenase (HPPD), or to herbicides selected from the group consisting of sulfonylureas, glyphosates, glufosinates or benzoylisoxazoles and similar active ingredients, or to any desired combinations of these active ingredients.

[0139] The compounds of the present invention can be particularly preferably used for transgenic crop plants resistant to combinations of glyphosates and glufosinates, glyphosates and sulfonylureas or imidazolinones. Most preferably, the compounds of the present invention can be used for transgenic crop plants, such as corn or soybeans with the trade name or name OptimumTM GATTM (tolerant to glyphosate ALS).

[0140] When the active ingredients of the invention are used in transgenic crops, not only the effects on harmful plants observed in other crops occur, but also generally effects specific to the application in a particular transgenic crop occur, such as a change or in particular a broadening of the spectrum of weeds that can be controlled, a change in the application rate that can be used for application, preferably good compatibility with herbicides to which the transgenic crop is resistant, and an influence on the growth and yield of the transgenic crop plants.

[0141] The present invention therefore also relates to the use of the compounds of the general formula (I) according to the invention as herbicides for controlling harmful plants in transgenic crop plants.

[0142] The compounds according to the invention can be applied in the form of wettable powders, emulsifiable concentrates, sprayable solutions, dusting products or granules in customary formulations. The invention therefore also provides herbicidal and plant growth regulating compositions containing the compounds according to the invention.

[0143] The compounds of the invention can be formulated in various ways, depending on the desired biological and / or physicochemical parameters. Possible formulations include, for example, wettable powders (WP), water-soluble powders (SP), water-soluble concentrates, emulsifiable concentrates (EC), emulsions (EW) such as oil-in-water emulsions and water-in-oil emulsions, sprayable solutions, suspension concentrates (SC), oil- or water-based dispersions, oil-soluble solutions, capsule suspensions (CS), dusting products (DP), seed dressings, granules for broadcasting and soil application, granules in microparticulate form (GR), spray granules, absorption and adsorption granules, water-dispersible granules (WG), water-soluble granules (SG), ULV preparations, microcapsules and waxes. These individual formulation types are known in principle and are described, for example, in Winnacker-Küchler, "Chemische Technologie" [Chemical Technology], Volume 7, C. Hanser Verlag Munich, 4th edition, 1986, Wade van Valkenburg, "Pesticide Formulations", Marcel Dekker, NY, 1973, K. Martens, "Spray Drying" Handbook, 3rd edition, 1979, G. Goodwin Ltd. London.

[0144] The required formulation auxiliaries, such as inert substances, surfactants, solvents and other additives are likewise known and described, for example, in: Watkins, "Handbook of Insecticide Dust Diluents and Carriers", 2nd edition, Darland Books, Caldwell NJ; HvOlphen, "Introduction to Clay Colloid Chemistry", 2nd edition, J. Wiley & Sons, NY; C. Marsden, "Solvents Guide", 2nd edition, Interscience, NY 1963; McCutcheon's "Detergents and Emulsifiers Annual", MCPubl.Corp., Ridgewood NJ; Sisley and Wood, "Encyclopedia of Surface Active Agents", Chem.Publ.Co.Inc., NY 1964; [Interface-active Ethylene Oxide Adducts], Wiss.Verlagsgesell, Stuttgart 1976; Winnacker-Küchler, "ChemischeTechnologie", Volume 7, C. Hanser Verlag Munich, 4th Edition, 1986.

[0145] Based on these formulations, combinations with other active ingredients (for example insecticides, acaricides, herbicides, fungicides) and with safeners, fertilizers and / or growth regulators can also be prepared, for example in the form of ready formulations or tank mixes.

[0146] The active ingredients that can be used in combination with the compounds of the present invention in the form of mixed formulations or tank mixes are, for example, known active ingredients based on inhibition of the following substances: for example, acetolactate synthase, acetyl-CoA carboxylase, cellulose synthase, enolpyruvylshikimate-3-phosphate synthase, glutamine synthase, p-hydroxyphenylpyruvate dioxygenase, phytoene desaturase, photosystem I, photosystem II or protoporphyrinogen oxidase, for example, as described in Weed Research 26 (1986) 441-445 or "The Pesticide Manual", 16th edition, The British Crop Protection Council and the Royal Soc. of Chemistry, 2006 and the literature cited therein. Known herbicides or plant growth regulators that can be combined with the compounds of the present invention are, for example, the following active ingredients, wherein the active ingredients are named according to the "common name" of the International Organization for Standardization (ISO), or are named by chemical name or code number. They always include all use forms, such as acids, salts, esters, and all isomeric forms, such as stereoisomers and optical isomers, even if not explicitly mentioned.

[0147] Examples of such herbicidal combinations are:

[0148] Acetochlor, acifluorfen, acifluorfen-sodium, aclonifen, alachlor, allidochlor, alloxydim, alloxydim-sodium, ametryn, amicarbazone, amidochlor, amidosulfuron, aminocyclopyrachlor, cyproconazole potassium salt ( aminocyclopyrachlor-potassium), aminocyclopyrachlor-methyl, aminopyralid, amitrole, ammoniumsulfamate, anilofos, asulam, atrazine, azafenidin, azimsulfuron, beflubutamid, benazolin, benazolin in-ethyl), benfluralin, benfuresate, bensulfuron, bensulfuron-methyl, bensulide, bentazone, benzobicyclon, benzofenap, bicyclopyron, bifenox, bilanafos, bilanafos-sodium, bispyribac, bispyribac-butyl ispyribac-sodium), bromacil, bromobutide, bromofenoxim, bromoxynil, bromoxynil-butyrate, bromoxynil-potassium, bromoxynil-heptanoate and bromoxynil-octanoate, busoxinone, butachlor, butafenacil,butamifos, butenachlor, butralin, butroxydim, butylate, cafenstrole, carbetamide, carfentrazone, carfentrazone-ethyl, chloramben, chlorbromuron, chlorfenac, chlorfenac-sodium, chlorfenpr op), chlorflurenol, chlorflurenol-methyl, chloridazon, chlorimuron, chlorimuron-ethyl, chlorophthalim, chlorotoluron, chlorthal-dimethyl, chlorsulfuron, 3-[5-chloro-4-(trifluoromethyl)pyridin-2-yl]-4-hydroxy-1-methylimidazolidin-2-one, cinidon, indole cinidon-ethyl, cinmethylin, cinosulfuron, clacyfos, clethodim, clodinafop, clodinafop-propargyl, clomazone, clomeprop, clopyralid, cloransulam, cloransulam-methyl, cumyluron, cyanamide amide), cyanazine, cycloate, cyclopyranil, cyclopyrimorate, cyclosulfamuron, cycloxydim, cyhalofop, cyhalofop-butyl, cyprazine, 2,4-D, 2,4-D-butotyl, 2,4-D-butyl, 2,4-D-dimethylammonium,2,4-D-diolamine, 2,4-D-ethyl, 2,4-D-2-ethylhexyl, 2,4-D-isobutyl, 2,4-D-isooctyl, 2,4-D-isopropylammonium, 2,4-D-potassium, 2,4-D-triisopropanolammonium and 2,4-D -triethanolamine (2,4-D-trolamine), 2,4-DB, 2,4-DB-butyl, 2,4-DB-dimethylammonium, 2,4-DB-isooctyl, 2,4-DB-potassium and 2,4-DB-sodium, daimuron (dymron), dalapon, dazomet, n-decanol, desmedi pham), detosyl-pyrazolate (DTP), dicamba, dichlobenil, 2-(2,4-dichlorobenzyl)-4,4-dimethyl-1,2-oxazolidin-3-one, 2-(2,5-dichlorobenzyl)-4,4-dimethyl-1,2-oxazolidin-3-one, dichlorprop, dichlorprop-P, diclofop, diclofop-methyl, diclofop-P-methyl, diclosulam 、difenzoquat、diflufenican、diflufenzopyr、diflufenzopyr-sodium、dimefuron、dimepiperate、dimethachlor、dimethametryn、dimethenamid、dimethenamid-P、dimetrasulfuron、dinitramine、dinoterb、diphenamid, diquat, diquat dibromide, dithiopyr, diuron, DNOC, endothal, EPTC, esprocarb, ethalfluralin, ethametsulfuron, ethametsulfuron-methyl, ethiozin, ethofumesate, ethoxyfen, ethoxyfen-ethyl, ethoxysulfuron (ethoxysulfuron), etobenzanid, F-9600, F-5231, i.e. N-[2-chloro-4-fluoro-5-[4-(3-fluoropropyl)-4,5-dihydro-5-oxo-1H-tetrazol-1-yl]phenyl]ethanesulfonamide, F-7967, i.e. 3-[7-chloro-5-fluoro-2-(trifluoromethyl)-1H-benzimidazol-4-yl]-1-methyl-6-(trifluoromethyl)pyrimidine-2,4(1H,3H)-dione, fenoxaprop, fenoxaprop-P, fenoxaprop-ethy l), fenoxaprop-P-ethyl, fenoxasulfone, fenquinotrione, fentrazamide, flamprop, flamprop-M-isopropyl, flamprop-M-methyl, flazasulfuron, florasulam, florpyrauxifen, florpyrauxifen-benz yl), fluazifop, fluazifop-P, fluazifop-butyl, fluazifop-P-butyl, flucarbazone, flucarbazone-sodium, flucetosulfuron, fluchloralin, flufenacet, flufenpyr, flufenpyr-ethyl,flumetsulam, flumiclorac, flumiclorac-pentyl, flumioxazin, fluometuron, flurenol, flurenol-butyl, flurenol-dimethylammonium, flurenol-methyl, fluoroglycofen, fluoroglycofen-ethyl, tetrafluoropropionic acid lupropanate), flupyrsulfuron, flupyrsulfuron-methyl-sodium, fluridone, flurochloridone, fluroxypyr, fluroxypyr-meptyl, flurtamone, fluthiacet, fluthiacet-methyl, fomesafen, fomesafen-sodium, foramsulfuron, fosamine, glufosinate, glufosinate-ammonium, glufosinate-sodium, glufosinate-ammonium, glufosinate-sodium, glyphosate, glyphosate-ammonium, glyphosate-isopropylammonium, glyphosate-diammonium, glyphosate-dimethylammonium, glyphosate-potassium -potassium), glyphosate-sodium and glyphosate-trimesium, H-9201, i.e. O-(2,4-dimethyl-6-nitrophenyl)-O-ethylisopropylthiophosphoramidate, halauxifen, halauxifen-methyl, halosafen, halosulfuron, halosulfuron-methyl, haloxyfop, haloxyfop-P,Haloxyfop-ethoxyethyl, haloxyfop-P-ethoxyethyl, haloxyfop-methyl, haloxyfop-P-methyl, hexazinone, HW-02, i.e. 1-(dimethoxyphosphoryl)ethyl (2,4-dichlorophenoxy)acetate, 4-hydroxy-1-methoxy-5-methyl-3-[4-(trifluoromethyl)pyridin-2-yl]imidazolidin-2-one, 4-hydroxy-1-methyl-3-[4-(trifluoromethyl)pyridin-2-yl]imidazolidin-2-one Ketone, imazamethabenz, imazamethabenz-methyl, imazamox, imazamox-ammonium, imazapic, imazapyr-ammonium, imazapyr, imazapyr-isopropylammonium, imazaquin, imazaquin-ammonium, imazethapyr pyr), imazethapyr-immonium, imazosulfuron, indanofan, indaziflam, iodosulfuron, iodosulfuron-methyl-sodium, ioxynil, ioxynil-octanoate, ioxynil-potassium and ioxynil-sodium, ipfencarbazon e), isoproturon, isouron, isoxaben, isoxaflutole, karbutilate, KUH-043 (3-({[5-(difluoromethyl)-1-methyl-3-(trifluoromethyl)-1H-pyrazol-4-yl]methyl}sulfonyl)-5,5-dimethyl-4,5-dihydro-1,2-oxazole, ketospiradox, lactofen, lenacil, linuron, MCPA, MCPA-butotyl,MCPA-dimethylammonium, MCPA-2-ethylhexyl, MCPA-isopropylammonium, MCPA-potassium, MCPA-sodium, MCPB, MCPB-methyl, MCPB-ethyl, MCPB-sodium, mecoprop, mecoprop op-sodium and mecoprop-butotyl, mecoprop-P, mecoprop-P-butotyl, mecoprop-P-dimethylammonium, mecoprop-P-2-ethylhexyl, mecoprop-P-potassium, mefenacet ... fluidide), mesosulfuron, mesosulfuron-methyl, mesotrione, methabenzthiazuron, metam, metamifop, metamitron, metazachlor, metazosulfuron, methabenzthiazuron, methiopyrsulfuron, methiozolin, methyl isothiocyanate, metobromuron, metolachlor, S-metolachlor, metosulam, metoxuron, metribuzin, metsulfuron, metsulfuron-methyl, molinat, monolinuron, monosulfuron, monosulfuron-ester,MT-5950, i.e. N-[3-chloro-4-(1-methylethyl)phenyl]-2-methylpentanamide, NGGC-011, napropamide, NC310, i.e. 4-(2,4-dichlorobenzoyl)-1-methyl-5-benzyloxypyrazole, neburon, nicosulfuron, nonanoic acid (pelargonic acid), norflurazon, oleic acid (fatty acid), orbencarb, orthosulfamuron, oryzalin, oxadiargyl, oxadiazon, oxasulfuron, oxaziclomefon, oxotrione (lancotrione), oxyfluorfen, paraquat, paraquat dichloride), pebulate, pendimethalin, penoxsulam, pentachlorophenol, pentoxazone, pethoxamid, petroleum oils, phenmedipham, picloram, picolinafen, pinoxaden, piperophos, pretilachlor, primisulfuron, primisulfuron-methyl, prodiamine, profoxydim, prometon, prometryn, propachl or), propanil, propaquizafop, propazine, propham, propisochlor, propoxycarbazone, propoxycarbazone-sodium, propyrisulfuron, propyzamide, prosulfocarb, prosulfuron, pyraclonil,Pyraflufen, pyraflufen-ethyl, pyrasulfotole, pyrazolynate (pyrazolate), pyrazosulfuron, pyrazosulfuron-ethyl, pyrazoxyfen, pyribambenz, pyribambenz-isopropyl, pyribambenz-propyl, pyribenzoxim, barnyardgrass pyributicarb, pyridafol, pyridate, pyriftalid, pyriminobac, pyriminobac-methyl, pyrimisulfan, pyrithiobac, pyrithiobac-sodium, pyroxasulfone, pyroxsulam, quinclorac, quinmerac, quinoclamine ), quizalofop, quizalofop-ethyl, quizalofop-P, quizalofop-P-ethyl, quizalofop-P-tefuryl, rimsulfuron, saflufenacil, sethoxydim, siduron, simazine, simetryn, sulcotrion, sulfentrazone, sulfentrazone sulfometuron, sulfometuron-methyl, sulfosulfuron, SYN-523, SYP-249, i.e. 1-ethoxy-3-methyl-1-oxobut-3-en-2-yl 5-[2-chloro-4-(trifluoromethyl)phenoxy]-2-nitrobenzoate, SYP-300, i.e. 1-[7-fluoro-3-oxo-4-(prop-2-yn-1-yl)-3,4-dihydro-2H-1,4-benzoxazin-6-yl]-3-propyl-2-thionemidazolidine-4,5-dione, 2,3,6-TBA, TCA (trifluoroacetic acid), sodium trifluoroacetate (TCA-sodium),tebuthiuron, tefuryltrione, tembotrione, tepraloxydim, terbacil, terbucarb, terbumeton, terbuthylazin, terbutryn, thenylchlor, thiazopyr, thiencarbazone, thiencarbazone-methyl, thifensulfuron, thifensulfuron-methyl, thiobencarb, tiafenacil, tolpyralate, topramezone, tralkoxydim, triafamone, wild tri-allate, triasulfuron, triaziflam, tribenuron, tribenuron-methyl, triclopyr, trietazine, trifloxysulfuron, trifloxysulfuron-sodium, trifludimoxazin, trifluralin, triflusulfuron, triflusulfuron-methyl, tritosulfuron, urea sulfate, vernolate, ZJ-0862 (3,4-dichloro-N-{2-[(4,6-dimethoxypyrimidin-2-yl)oxy]benzyl}aniline), flufenacet, quinpyraclostrobin, lancotrione, and the following compounds:

[0149]

[0150] In the context of the present specification, if the abbreviation of the common name of the active compound is used, all customary derivatives, such as esters and salts, and isomers, in particular optical isomers, in particular one or more commercially available forms are included in each case. If the common name denotes an ester or a salt, all other customary derivatives, such as other esters and salts, free acids and neutral compounds, and isomers, in particular optical isomers, in particular one or more commercially available forms are also included in each case. The chemical name of a compound given denotes at least one compound covered by the common name, generally a preferred compound.

[0151] When used, if necessary, commercially available preparations are diluted in a common manner, for example, in the case of wettable powders, concentrated emulsions, suspensions and particles suspended in water, water dilution is used. Powders, granules used for soil application or solutions for broadcasting and spraying generally do not need to be further diluted with inert substances before use. The required use amount of the compound of formula I is also different as external conditions change, and external conditions are, for example, the properties of the herbicide used, such as temperature, humidity, etc. It can have a large range of variation, for example, between 0.001 and 1.0 kg / ha, or more active substances, but preferably between 0.005 and 750 g / ha, particularly between 0.005 and 500 g / ha.

[0152] The term "aryl" refers to a 6 to 14-membered all-carbon monocyclic or fused polycyclic (i.e., a ring that shares adjacent pairs of carbon atoms) group having a conjugated π electron system, preferably 6 to 10 members, such as phenyl and naphthyl. More preferably phenyl. The aryl ring may be fused to a heteroaryl, heterocyclyl or cycloalkyl ring, wherein the ring connected to the parent structure is an aryl ring. The aryl group may be substituted or unsubstituted, and when substituted, the substituent is preferably one or more of the following groups, which are independently selected from alkyl, alkenyl, alkynyl, alkoxy, alkylthio, alkylamino, halogen, sulfhydryl, hydroxyl, nitro, cyano, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, cycloalkyloxy, heterocycloalkyloxy, cycloalkylthio, heterocycloalkylthio, carboxyl or carboxylate.

[0153] The term "heteroaryl" refers to a heteroaromatic system containing 1 to 4 heteroatoms and 5 to 14 ring atoms, wherein the heteroatoms are selected from oxygen, sulfur and nitrogen. The heteroaryl is preferably 5 to 10-membered, more preferably 5-membered or 6-membered, such as imidazolyl, furanyl, thienyl, thiazolyl, pyrazolyl, oxazolyl, pyrrolyl, triazolyl, tetrazolyl, pyridyl, pyrimidyl, thiadiazole, pyrazinyl, etc., preferably triazolyl, thienyl, imidazolyl, pyrazolyl, pyridyl, pyrimidyl and thiazolyl; more preferably triazolyl, pyrrolyl, thienyl, thiazolyl, pyridyl and pyrimidyl. The heteroaryl ring can be fused to an aryl, heterocyclic or cycloalkyl ring, wherein the ring connected to the parent structure is a heteroaryl ring. The heteroaryl group may be optionally substituted or unsubstituted, and when substituted, the substituents are preferably one or more groups independently selected from alkyl, alkenyl, alkynyl, alkoxy, alkylthio, alkylamino, halogen, mercapto, hydroxy, nitro, cyano, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, cycloalkyloxy, heterocycloalkyloxy, cycloalkylthio, heterocycloalkylthio, carboxyl or carboxylate.

[0154] The term "cycloalkyl" refers to a saturated or partially unsaturated monocyclic or polycyclic cyclic hydrocarbon substituent, wherein the cycloalkyl ring contains 3 to 20 carbon atoms, preferably 3 to 12 carbon atoms, more preferably 3 to 8 carbon atoms, and most preferably 3 to 6 carbon atoms. Non-limiting examples of monocyclic cycloalkyls include cyclopropyl, cyclobutyl, cyclopentyl, cyclopentenyl, cyclohexyl, cyclohexenyl, cyclohexadienyl, cycloheptyl, cycloheptatrienyl, cyclooctyl, etc.; polycyclic cycloalkyls include cycloalkyls of spirocyclic, fused and bridged rings, preferably cyclopropyl, cyclobutyl, cyclohexyl, cyclopentyl and cycloheptyl.

[0155] The cycloalkyl ring may be fused to an aryl, heteroaryl or heterocycloalkyl ring, wherein the ring attached to the parent structure is a cycloalkyl, non-limiting examples of which include indanyl, tetrahydronaphthyl, benzocycloheptanyl, etc. The cycloalkyl may be optionally substituted or unsubstituted, and when substituted, the substituents are preferably one or more of the following groups independently selected from alkyl, alkenyl, alkynyl, alkoxy, alkylthio, alkylamino, halogen, mercapto, hydroxy, nitro, cyano, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, cycloalkyloxy, heterocycloalkyloxy, cycloalkylthio, heterocycloalkylthio, oxo, carboxyl or carboxylate.

[0156] The term "heterocyclyl" refers to a saturated or partially unsaturated monocyclic or polycyclic hydrocarbon substituent containing 3 to 20 ring atoms, one or more of which are heteroatoms selected from nitrogen, oxygen or S(O)m (wherein m is an integer from 0 to 2), but excluding the ring part of -OO-, -OS- or -SS-, and the remaining ring atoms are carbon. Preferably, it contains 3 to 12 ring atoms, of which 1 to 4 are heteroatoms; more preferably, it contains 3 to 8 ring atoms; and most preferably, it contains 3 to 8 ring atoms. Non-limiting examples of monocyclic heterocyclic groups include oxetane, pyrrolidinyl, pyrrolidinone, imidazolidinyl, tetrahydrofuranyl, tetrahydrothienyl, dihydroimidazolyl, dihydrofuranyl, dihydropyrazolyl, dihydropyrrolyl, piperidinyl, piperazinyl, morpholinyl, thiomorpholinyl, homopiperazinyl, pyranyl, etc., preferably oxetane, pyrrolidinone, tetrahydrofuranyl, pyrazolidinyl, morpholinyl, piperazinyl and pyranyl. Polycyclic heterocyclic groups include spirocyclic, condensed ring and bridged heterocyclic groups; wherein the spirocyclic, condensed ring and bridged heterocyclic groups involved are optionally connected to other groups by single bonds, or further connected to other cycloalkyl, heterocyclic, aryl and heteroaryl groups by any two or more atoms on the ring.

[0157] The heterocyclyl ring may be fused to an aryl, heteroaryl or cycloalkyl ring, wherein the ring connected to the parent structure is a heterocyclyl. The heterocyclyl may be optionally substituted or unsubstituted, and when substituted, the substituent is preferably one or more of the following groups independently selected from alkyl, alkenyl, alkynyl, alkoxy, alkylthio, alkylamino, halogen, sulfhydryl, hydroxyl, nitro, cyano, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, cycloalkyloxy, heterocycloalkyloxy, cycloalkylthio, heterocycloalkylthio, oxo, carboxyl or carboxylate.

[0158] If there is a conflict between the Chinese name and the structural formula of the compound in the present invention, the structural formula shall prevail, unless there is an obvious error in the structural formula.

[0159] The beneficial effects of the present invention are as follows: providing a 4-methylsulfonylbenzamide compound having a sulfur-containing substituent at the 3rd position, a preparation method, a herbicidal composition and use thereof; the compound has excellent herbicidal activity and higher crop safety, and especially establishes good selectivity for key crops such as wheat, rice and corn; and the preparation method of the herbicide of the present invention is simple to operate and low in cost, and is suitable for large-scale industrial production. DETAILED DESCRIPTION

[0160] The following examples are used to illustrate the present invention and should not be regarded as limiting the present invention in any way. The scope of rights claimed for protection by the present invention is described by the claims. In the art, simple replacements or improvements made by technicians in the present invention are all within the technical solutions protected by the present invention.

[0161] Several methods for preparing the compounds of the present invention are described in detail in the following schemes and examples. The raw materials can be purchased from the market or can be prepared by methods known in the literature or as shown in the detailed description. It will be appreciated by those skilled in the art that other synthetic routes can also be used to synthesize the compounds of the present invention. Although the specific raw materials and conditions in the synthetic route have been described below, it can be easily replaced with other similar raw materials and conditions, and these modifications or variations of the preparation method of the present invention such as various isomers of the compound are included within the scope of the present invention. In addition, the preparation method described below can be further modified according to the disclosure of the present invention using conventional chemical methods well known to those skilled in the art. For example, appropriate groups are protected during the reaction, etc.

[0162] The method examples provided below are used to promote further understanding of the preparation method of the present invention, and the specific substances, types and conditions used are determined to be further explanations of the present invention and are not intended to limit the reasonable scope thereof. The reagents used in the synthetic compounds described below can be purchased commercially or can be easily prepared by a person of ordinary skill in the art.

[0163] The analytical instruments described in the examples are as follows:

[0164] 1. High performance liquid chromatography (HPLC): Agilent Technologies, 1260 Infinity II equipment

[0165] Column: Agilent Eclipse Plus C18 3.5μm, 4.6*100mm

[0166] Mobile phase: A: water + 0.1% phosphoric acid; B: acetonitrile, temperature: 30°C

[0167] Gradient: 10% B to 95% B in 15 min; 95% B 3 min

[0168] Flow rate: 1mL / min

[0169] 2. Ultra-high performance liquid chromatography-tandem mass spectrometry (hereinafter referred to as LC-MS): Waters, ACQUITY H-Class UPLC-SQ Detector 2 equipment

[0170] column: BEH C18 1.7μm,2.1*50mm Column

[0171] Mobile phase: A: water + 0.2% formic acid; B: acetonitrile, temperature: 30°C

[0172] Gradient: 10% B to 95% B in 5 min; 95% B 1 min

[0173] Flow rate: 0.5mL / min

[0174] MS method: ESI positive, negative, mass range (m / z): 100-800

[0175] 3. Gas chromatography-tandem mass spectrometer (hereinafter referred to as GC-MS): Agilent Technologies, 7890B GCSystem-5977A MSD equipment

[0176] Column: Agilent Technologies, HP-5MS UI 0.25μm, 30m*0.250mm

[0177] Injector temperature: 250°C

[0178] Chromatographic column flow rate: Helium 1mL / min

[0179] Method: Keep at 40℃ for 2 minutes, increase the temperature to 280℃ at 20℃ / min, keep at 280℃ for 5 minutes, total time 19 minutes

[0180] MSD transfer line temperature: 280°C

[0181] EI ion source temperature: 230°C, MS quadrupole temperature: 150°C, scan range: 30.00-400.00

[0182] In addition, the proton nuclear magnetic resonance spectrum (hereinafter referred to as 1 The chemical shift values ​​of H-NMR were measured at 400 MHz (Bruker, AVANCE IIIHD 400M) in deuterated chloroform solvent (CDCl3) using Me4Si (tetramethylsilane) as the reference substance. When measured in deuterated dimethyl sulfoxide solvent, the chemical shift value data are displayed as "(DMSO-d6)". It should be noted that 1 The symbols in the chemical shift values ​​of H-NMR have the following meanings:

[0183] s: singlet, d: doublet, dd: doublet of doublets, dt: doublet of triplets, td: triplet of doublets, ddd: doublet of doublets, t: triplet, q: quartet, sep: septet, m: multiplet, brs: broad singlet. In addition, when there are two or more stereoisomers, each chemical shift value is marked with "and" for the resolvable signal.

[0184] Examples of representative compounds are as follows. The synthesis methods of other compounds are similar and will not be described in detail here.

[0185] Intermediate 1

[0186] 2-Chloro-3-mercapto-4-methylsulfonylbenzoic acid

[0187]

[0188] At room temperature, add the compound 2-chloro-3-fluoro-4-methylsulfonylbenzoic acid (40.00 g, 0.16 mol) and N-methylpyrrolidone (400 mL) to a 1L reaction bottle, heat to 55 ° C, add sodium hydrosulfide (63.4 g, 0.79 mol) in batches, and continue to react for 0.5 hours after the addition is completed. After the reaction is completed, pour the reaction solution into a large amount of ice water, adjust the pH to 1 with hydrochloric acid, precipitate the solid, filter, and dry in an oven at 45 ° C to obtain a crude mixture of intermediate 1 (white solid, 37.60 g), which is directly used in the next step without further purification. Take part of the crude mixture of intermediate 1 and prepare it by reverse phase high pressure to obtain the nuclear magnetic data:

[0189] 1 H NMR (400MHz, CD3CN-d3) δ8.07(d,J=8.2Hz,1H),7.67(d,J=8.3Hz,1H),5.65(brs,1H),3.25(s,3H).

[0190] Intermediate 2

[0191] 2-Chloro-4-methylsulfonyl-3-propylthiobenzoic acid

[0192]

[0193] At room temperature, compound 2,3-dichloro-4-methylsulfonylbenzoic acid (200 mg, 0.74 mmol), potassium hydroxide (166 mg, 2.96 mmol), cesium carbonate (968 mg, 4.91 mmol), dimethyl sulfoxide (4 mL), tetrabutylammonium bromide (15 mg, 0.05 mmol) and potassium iodide (15 mg, 0.09 mmol) were added to a 50 mL single-mouth bottle, cooled to 5 ° C in an ice bath, and propanethiol (200 mg, 2.63 mmol) was slowly added dropwise. After the addition was completed, it was stirred at room temperature overnight. After the reaction was completed, 5% dilute hydrochloric acid was added dropwise to adjust the pH value to 1-2, and 10 mL of ethyl acetate was extracted twice. After the organic phase was combined, it was washed once with saturated brine. Drying over anhydrous sodium sulfate and distilling off the solvent under reduced pressure to obtain a crude mixture of intermediate 2 (yellow solid, 210 mg), which was directly used in the next step without further purification. Take part of the crude mixture of intermediate 2 and prepare it by reverse phase high pressure to obtain the NMR data:

[0194] 1H NMR (400MHz, DMSO-d6) δ8.09(d,J=7.0Hz,1H),7.89(d,J=7.0Hz,1H),3.55(s,3H),2.97(t,J=7.4Hz,2H),1.61(q,J=7.4Hz,2H),0.97(t,J=7.3Hz,3H).

[0195] Intermediate 3

[0196] 2-Chloro-4-methylsulfonyl-3-propylsulfinylbenzoic acid

[0197]

[0198] At room temperature, intermediate 2 (200 mg, 0.65 mmol) and dichloromethane (5 mL) were added to a 25 mL single-mouth bottle, cooled to 5 ° C in an ice bath, and 85% m-chloroperbenzoic acid (131.49 mg, 0.65 mmol) was added in batches. After the addition was completed, the mixture was stirred in an ice bath for 30 minutes. After the reaction was completed, solid impurities were filtered out, and peroxides were removed by washing with saturated sodium bisulfite. The solvent was evaporated under reduced pressure, and intermediate 3 (white solid, 68 mg) was purified by silica gel column flash column chromatography.

[0199] 1 H NMR (400MHz, DMSO-d6) δ8.08(d,J=8.1Hz,1H),8.00(d,J=8.1Hz,1H),3.87-3.65( m,1H),3.51(s,3H),3.12-3.01(m,1H),1.91-1.69(m,2H),1.07(t,J=7.4Hz,3H).

[0200] Intermediate 4

[0201] 2-Chloro-4-methylsulfonyl-3-propylsulfonylbenzoic acid

[0202]

[0203] At room temperature, add intermediate 2 (200 mg, 0.65 mmol), acetic acid (5 mL), sodium tungstate (9.55 mg, 0.03 mmol) to a 25 mL single-mouth bottle, heat to 90 ° C, add 30% hydrogen peroxide (1473.33 mg, 13 mmol), and stir for 2 hours after the addition is complete. After the reaction is completed, the solvent is evaporated under reduced pressure, 10 mL of ethyl acetate is added to dissolve, dried over anhydrous sodium sulfate, filtered, and the solvent is evaporated under reduced pressure to obtain a crude mixture of intermediate 4 (white solid, 205 mg), which is directly used as a crude intermediate for the next step without further purification. Take part of the crude mixture of intermediate 4 and prepare it by reverse phase high pressure to obtain the following nuclear magnetic data:

[0204] 1 H NMR (400MHz, DMSO-d6) δ8.29(d,J=8.2Hz,1H),8.08(d,J=8.2Hz,1H),3.71-3.64(m,2H),3.61(s,3H),1.96-1.82(m,2H),1.04(t,J=7.4Hz,3H).

[0205] Intermediate 5

[0206] 2-Chloro-3-isopropylthio-4-methylsulfonylbenzoic acid

[0207]

[0208] At room temperature, add the compound 2-chloro-3-fluoro-4-methylsulfonylbenzoic acid (3.50g, 13.85mmol), dimethyl sulfoxide (30mL), and potassium hydroxide (2.30g, 40.99mmol) to a 100mL single-mouth bottle, cool to 10°C in an ice bath, and add 2-propanethiol (2.10g, 27.58mmol) dropwise. After the addition is complete, stir at room temperature for 0.5 hours. After the reaction is completed, add 60mL of water, extract twice with 20mL of ethyl acetate, combine the organic phases, wash once with saturated brine, and evaporate the solvent under reduced pressure to obtain a crude mixture of intermediate 5 (yellow solid, 4.14g), which is directly used in the next step without further purification. Take part of the crude mixture of intermediate 5 and prepare it by reverse phase high pressure to obtain the following nuclear magnetic data:

[0209] 1 H NMR (400MHz, DMSO-d6) δ8.17(d,J=8.1Hz,1H),7.94(d,J=8.2Hz,1H),3.84(p,J=6.7Hz,1H),3.59(s,3H),1.28(d,J=6.7Hz,6H).

[0210] Intermediate 29

[0211] Methyl 2-chloro-3-mercapto-4-methylsulfonylbenzoate

[0212]

[0213] At room temperature, intermediate 1 (5 g, 18.75 mol) and methanol (150 mL) were added to a 250 mL single-mouth bottle, cooled to -10 ° C, and concentrated sulfuric acid (5 mL) was slowly added dropwise. After the addition was complete, the temperature was raised to 60 ° C and stirred under reflux overnight. After the reaction was completed, the reaction solution was poured into 200 mL of ice water, filtered and dried to obtain a crude mixture of intermediate 29 (off-white solid, 4.70 g), which was directly used in the next step without further purification.

[0214] Intermediate 30

[0215] Methyl 2-chloro-3-cyclopropylthio-4-methylsulfonylbenzoate

[0216]

[0217] At room temperature, intermediate 29 (5.00 g, 17.81 mmol), dichloroethane (45 mL), 2,2'-bipyridine (3.34 g, 21.39 mmol), copper acetate (3.56 g, 17.81 mmol), cyclopropylboronic acid (3.32 g, 38.60 mol) were added to a 125 mL pressure bottle, heated to 70 ° C and stirred for 4 hours. After the reaction was completed, 200 mL of ammonia water (25%) was added, stirred for 15 minutes, extracted with 25 mL of dichloromethane 3 times, washed with water twice, filtered to remove solid impurities, and concentrated to obtain a crude mixture of intermediate 30 (white solid, 4.87 g), which was used directly in the next step without further purification.

[0218] Intermediate 31

[0219] 2-Chloro-3-cyclopropylthio-4-methylsulfonylbenzoic acid

[0220]

[0221] At room temperature, add intermediate 30 (4.87 g, 14.46 mmol), tetrahydrofuran (25 mL), and water (10 mL) into a 50 mL single-mouth bottle, cool to 5 ° C, slowly add lithium hydroxide monohydrate (1.8 g, 42.90 mol), and stir at room temperature for 2 hours after the addition is complete. After the reaction is completed, the solvent is evaporated under reduced pressure, 30 mL of water is added to dissolve, and 10 mL of dichloromethane is used to extract twice. 5% dilute hydrochloric acid is added to the aqueous phase to adjust the pH value to 1-2, and dried over anhydrous sodium sulfate. Extract twice with 15 mL of ethyl acetate, dry over anhydrous sodium sulfate, and concentrate to obtain a crude mixture of intermediate 31 (white solid, 4.72 g), which is directly used in the next step without further purification. Take part of the crude mixture of intermediate 31 and prepare it by reverse phase high pressure to obtain the following nuclear magnetic data:

[0222] 1 H NMR (400MHz, DMSO-d6) δ8.08(d,J=8.2Hz,1H),7.88(d,J=8.2Hz,1H),3.45(s,3H),2.70-2.63(m,1H),0.92-0.86(m,2H),0.79-0.73(m,2H).

[0223] Intermediate 32

[0224] 2-Chloro-3-cyclopropylsulfinyl-4-methylsulfonylbenzoic acid

[0225]

[0226] At room temperature, intermediate 31 (198.49 mg, 0.65 mmol), acetic acid (5 mL), sodium tungstate (9.55 mg, 0.03 mmol) were added to a 25 mL single-mouth bottle, the temperature was raised to 50°C, 30% hydrogen peroxide (110.50 mg, 0.98 mmol) was added dropwise, and after the addition was completed, the mixture was stirred for 2 hours. After the reaction was completed, the solvent was evaporated under reduced pressure, 10 mL of ethyl acetate was added to dissolve, the mixture was dried over anhydrous sodium sulfate, filtered, the solvent was evaporated under reduced pressure, and intermediate 32 (white solid, 158.79 mg) was prepared by reverse phase high pressure.

[0227] 1 H NMR (400MHz, DMSO-d6) δ8.08(d,J=8.2Hz,1H),7.89(d,J=8.1Hz,1H),3.48(s,3H),3.38-3.34(m,1H),1.28-1.17(m,2H),1.09-0.95(m,2H).

[0228] Intermediate 33

[0229] 2-Chloro-3-cyclopropylsulfonyl-4-methylsulfonylbenzoic acid

[0230]

[0231] At room temperature, intermediate 31 (198.49 mg, 0.65 mmol) and dichloroethane (5 mL) were added to a 25 mL single-mouth bottle, heated to 50°C, and 85% m-chloroperbenzoic acid (277.13 mg, 1.36 mmol) was added in batches. After the addition was completed, the mixture was stirred for 30 minutes. After the reaction was completed, solid impurities were removed by filtration, and peroxides were removed by washing with saturated sodium bisulfite. The solvent was evaporated under reduced pressure, and intermediate 33 (white solid, 158 mg) was purified by silica gel column flash column chromatography.

[0232] 1 H NMR (400MHz, DMSO-d6) δ8.36(d,J=8.3Hz,1H),8.11(d,J=8.3Hz,1H),3.61(s,3H),3.48-3.40(m,1H),1.49-1.43(m,2H),1.24-1.17(m,2H).

[0233] Intermediate 34

[0234] 2-Chloro-3-cyclobutylthio-4-methylsulfonylbenzoic acid

[0235]

[0236] At room temperature, add intermediate 1 (1.50g, 5.62mmol), potassium carbonate (2.34g, 16.92mmol), and N,N-dimethylformamide (15mL) into a 250mL single-mouth bottle, heat to 40°C, slowly drop cyclobutane bromide (0.72g, 5.36mmol), and stir at room temperature for 10 hours after the addition is complete. After the reaction is completed, add 5% dilute hydrochloric acid to adjust the pH value to 1-2, extract twice with 10mL of ethyl acetate, combine the organic phases, and wash once with saturated brine. Dry over anhydrous sodium sulfate, evaporate the solvent under reduced pressure, and obtain a crude mixture of intermediate 34 (yellow solid, 1.91g), which is used directly in the next step without further purification. Take part of the crude mixture of intermediate 34 and prepare it by reverse phase high pressure to obtain the following nuclear magnetic data:

[0237] 1 H NMR (400MHz, DMSO-d6) δ7.89(d,J=8.2Hz,1H),7.65(d,J=8.2Hz,1H),3.74(p,J=8 .2Hz,1H),3.34(s,3H),2.18-2.06(m,2H),2.02-1.88(m,2H),1.78-1.57(m,2H).

[0238] Intermediate 40

[0239] 2-Chloro-3-cyclohexylthio-4-methylsulfonylbenzoic acid

[0240]

[0241] At room temperature, compound 2-chloro-3-fluoro-4-methylsulfonylbenzoic acid (3.50 g, 13.85 mol), dimethyl sulfoxide (30 mL), potassium hydroxide (2.30 g, 40.99 mmol) were added to a 100 mL single-mouth bottle, cooled to 10 ° C in an ice bath, and cyclohexanethiol (3.20 g, 27.53 mmol) was added dropwise. After the addition was completed, it was stirred at room temperature for 0.5 hours. After the reaction was completed, 60 mL of water was added, and 20 mL of ethyl acetate was extracted twice. After the organic phase was combined, it was washed once with saturated brine, and the solvent was evaporated under reduced pressure to obtain a crude mixture of intermediate 40 (yellow solid, 4.30 g), which was directly used in the next step without further purification. Take part of the crude mixture of intermediate 40 and prepare it by reverse phase high pressure to obtain the following nuclear magnetic data:

[0242] 1H NMR(400MHz,DMSO-d6)δ8.10(d,J=8.1Hz,1H),7.86(d,J=8.2Hz,1H),3.55-3.43(m ,4H),1.81-1.67(m,4H),1.59-1.53(m,1H),1.50-1.37(m,2H),1.31-1.12(m,3H).

[0243] Intermediate 43

[0244] 2-Chloro-4-methylsulfonyl-3-(2,2,2-trifluoroethyl)thiobenzoic acid

[0245]

[0246] At room temperature, add intermediate 1 (1.50 g, 5.64 mmol), potassium carbonate (2.34 g, 16.92 mmol), and N,N-dimethylformamide (15 mL) into a 250 mL single-mouth bottle, cool to 5 ° C, slowly add 2,2,2-trifluoroethyl trifluoromethanesulfonate (1.31 g, 5.64 mmol), and stir at room temperature for 2 hours after the addition is complete. After the reaction is completed, add 5% dilute hydrochloric acid to adjust the pH value to 1-2, extract twice with 10 mL of ethyl acetate, combine the organic phases, and wash once with saturated brine. Dry over anhydrous sodium sulfate, evaporate the solvent under reduced pressure, and obtain a crude mixture of intermediate 43 (white solid, 2.12 g), which is used directly in the next step without further purification. Take part of the crude mixture of intermediate 43 and prepare it by reverse phase high pressure to obtain the following nuclear magnetic data:

[0247] 1 H NMR (400MHz, DMSO-d6) δ8.10(d,J=8.1Hz,1H),7.91(d,J=8.1Hz,1H),4.01(q,J=10.6Hz,2H),3.52(s,3H).

[0248] Intermediate 44

[0249] 2-Chloro-4-methylsulfonyl-3-(2,2,2-trifluoroethyl)sulfinylbenzoic acid

[0250]

[0251] At room temperature, intermediate 43 (226.68 mg, 0.65 mmol) and dichloroethane (5 mL) were added to a 25 mL single-mouth bottle, heated to 50°C, and 85% m-chloroperbenzoic acid (277.13 mg, 0.72 mmol) was added in batches. After the addition was completed, the mixture was stirred for 30 minutes. After the reaction was completed, solid impurities were removed by filtration, and peroxides were removed by washing with saturated sodium bisulfite. The solvent was evaporated under reduced pressure, and high-pressure reverse phase purification was performed to obtain intermediate 44 (white solid, 181.35 mg).

[0252] Intermediate 49

[0253] 3-Allylthio-2-chloro-4-methylsulfonylbenzoic acid

[0254]

[0255] At room temperature, add intermediate 1 (1.50 g, 5.64 mmol), potassium carbonate (2.34 g, 16.92 mmol), and N,N-dimethylformamide (15 mL) into a 250 mL single-mouth bottle, cool to 0 ° C in an ice bath, slowly add 3-bromopropylene (750.56 mg, 6.21 mmol), and stir at room temperature for 1 hour after the addition is complete. After the reaction is completed, add 5% dilute hydrochloric acid to adjust the pH value to 1-2, extract twice with 10 mL of ethyl acetate, combine the organic phases, and wash once with saturated brine. Dry over anhydrous sodium sulfate, evaporate the solvent under reduced pressure, and obtain a crude mixture of intermediate 49 (yellow solid, 1.65 g), which is used directly in the next step without further purification. Take part of the crude mixture of intermediate 49 and prepare it by reverse phase high pressure to obtain the following nuclear magnetic data:

[0256] 1 H NMR (400MHz, DMSO-d6) δ8.07(d,J=8.2Hz,1H),7.86(d,J=8.2Hz,1H),5.94-5.79(m,1H),5.11-4.98(m,2H),3.72(d,J=7.4Hz,2H),3.53(s,3H).

[0257] Intermediate 51

[0258] 3-Allylsulfonyl-2-chloro-4-methylsulfonylbenzoic acid

[0259]

[0260] At room temperature, intermediate 49 (199.41 mg, 0.65 mmol), acetic acid (5 mL), sodium tungstate (9.55 mg, 0.03 mmol) were added to a 25 mL single-mouth bottle, heated to 50°C, and 30% hydrogen peroxide (162.07 mg, 1.43 mmol) was added dropwise. After the addition was complete, the mixture was stirred for 2 hours. After the reaction was completed, the solvent was evaporated under reduced pressure, 10 mL of ethyl acetate was added to dissolve, dried over anhydrous sodium sulfate, filtered, and the solvent was evaporated under reduced pressure to obtain intermediate 51 (white solid, 159.53 mg) by reverse phase high pressure.

[0261] 1 H NMR (400MHz, DMSO-d6) δ8.33(d,J=8.2Hz,1H),8.12(d,J=8.2Hz,1H),6.01-5.86(m,1H),5.52-5.42(m,2H),4.50(d,J=7.4Hz,2H),3.62(s,3H).

[0262] The intermediates in Table 1-1 can be prepared by referring to the synthetic methods similar to the above intermediates:

[0263] Table 1-1

[0264]

[0265]

[0266]

[0267]

[0268]

[0269]

[0270]

[0271]

[0272]

[0273]

[0274] Example 1-1

[0275] 2-Chloro-N-(1-methyl-1H-tetrazol-5-yl)-4-methylsulfonyl-3-propylthiobenzamide

[0276]

[0277] At room temperature, intermediate 2 (120 mg, 0.39 mmol), 1-methyl-5-aminotetrazole (50.55 mg, 0.45 mmol), pyridine (4 mL) and N-methylimidazole (63.88 mg, 0.78 mmol) were added to a 50 mL single-mouth bottle, cooled to 5 ° C in an ice bath, and oxalyl chloride (98.75 mg, 0.78 mmol) was slowly added dropwise. After the addition was completed, it was stirred at 0 ° C for 30 minutes, and then the reaction solution was heated to 55 ° C and stirred for 1 hour. After the reaction was completed, pyridine was removed by rotary evaporation, water was added to the reaction bottle, 5% dilute hydrochloric acid was added dropwise to adjust the pH value to 1-2, and 15 mL of ethyl acetate was extracted twice. After the organic phase was combined, it was washed once with saturated brine. Drying with anhydrous sodium sulfate, the solvent was evaporated under reduced pressure, and compound 1-1 (white solid, 90 mg) was obtained by silica gel column flash column chromatography.

[0278] 1 H NMR (400MHz, DMSO-d6) δ12.01(s,1H),8.16(d,J=8.1Hz,1H),8.00(d,J=8.1Hz,1H),4.03 (s,3H),3.58(s,3H),3.00(t,J=7.4Hz,2H),1.64(q,J=7.4Hz,2H),0.98(t,J=7.3Hz,3H).

[0279] Example 1-2

[0280] 2-Chloro-N-(1-methyl-1H-tetrazol-5-yl)-4-methylsulfonyl-3-propylsulfinylbenzamide

[0281]

[0282] At room temperature, compound 1-1 (90 mg, 0.22 mmol) and dichloromethane (5 mL) were added to a 25 mL single-mouth bottle, cooled to 5 ° C in an ice bath, and 85% m-chloroperbenzoic acid (45.27 mg, 0.22 mmol) was added in batches. After the addition was completed, the mixture was stirred in an ice bath for 1 hour. After the reaction was completed, solid impurities were filtered out, and peroxides were removed by washing with saturated sodium bisulfite. The solvent was evaporated under reduced pressure, and compound 1-2 (white solid, 45 mg) was obtained by silica gel column flash column chromatography.

[0283] 1H NMR (400MHz, DMSO-d6) δ12.07(s,1H),8.20-8.10(m,2H),4.03(s,3H),3.74(ddd,J=12.9,7.9,5 .0Hz,1H),3.55(s,3H),3.08(dt,J=12.7,8.1Hz,1H),1.91-1.74(m,2H),1.08(t,J=7.4Hz,3H).

[0284] Examples 1-3 and 1-4

[0285] 1-2-racemate (130 mg, 99% purity) was purified by chiral HPLC (Column: AD-H; Column Size: 3cm×25cm, 5μm; Injection: 4mL; Mobile phase: Hex: EtOH (0.1% FA) = 65:35; Flow rate: 43mL / min; Wavelength: UV 220nm; Temperature: 25℃; Sample solution: 6mg / mL in Hex / EtOH; Run time: 25mins) was separated and concentrated to obtain compound 1-3 (59mg, Rt = 15.01min, 100% ee, purity 99.7%, [α] D 20 = +100.30° (c 0.100, DMF)) and compound 1-4 (60 mg, Rt = 11.35 min, 100% ee, purity 99.6%, [α] D 20 = -106.54° (c 0.101, DMF)).

[0286] Examples 1-5

[0287] 2-Chloro-N-(1-methyl-1H-tetrazol-5-yl)-4-methylsulfonyl-3-propylsulfonylbenzamide

[0288]

[0289] At room temperature, intermediate 4 (132.61 mg, 0.39 mmol), 1-methyl-5-aminotetrazole (50.55 mg, 0.45 mmol), pyridine (4 mL) and N-methylimidazole (63.88 mg, 0.79 mmol) were added to a 50 mL single-mouth bottle, cooled to 5 ° C in an ice bath, and oxalyl chloride (98.75 mg, 0.79 mmol) was slowly added dropwise. After the addition was completed, it was stirred at 0 ° C for 30 minutes, and then the reaction solution was heated to 55 ° C and stirred for 1 hour. After the reaction was completed, pyridine was removed by rotary evaporation, water was added to the reaction bottle, 5% dilute hydrochloric acid was added dropwise to adjust the pH value to 1-2, and 15 mL of ethyl acetate was extracted twice. After the organic phase was combined, it was washed once with saturated brine. Drying over anhydrous sodium sulfate, the solvent was evaporated under reduced pressure, and high-pressure reverse phase purification was obtained to obtain compound 1-5 (white solid, 65 mg).

[0290] 1 H NMR (400MHz, DMSO-d6) δ12.09(s,1H),8.40(d,J=8.1Hz,1H),8.31(d,J=7.6Hz,1H),4.0 3(s,3H),3.70(t,J=7.6Hz,2H),3.66(s,3H),1.96-1.84(m,2H),1.06(t,J=7.4Hz,3H).

[0291] Examples 1-8 and 1-9

[0292] Compound 1-7 (110 mg, 99% purity) was purified by chiral HPLC (Column: AD-H; Column Size: 3cm×25cm, 5μm; Injection: 4mL; Mobile phase: Hex: EtOH (0.1% FA) = 65:35; Flow rate: 43mL / min; Wavelength: UV 220nm; Temperature: 25℃; Sample solution: 3mg / mL in Hex / EtOH / MeOH; Run time: 25mins) was separated and concentrated to obtain compound 1-8 (46mg, Rt = 14.14min, 100% ee, purity 99.8%, [α] D 20 = +58.73° (c 0.116, DMF)) and compound 1-9 (54 mg, Rt = 9.59 min, 100% ee, purity 99.7%, [α] D 20 = -64.82° (c 0.104, DMF).

[0293] Examples 1-17 and 1-18

[0294] Compound 1-16 (430 mg, 99% purity) was purified by chiral HPLC (Column: AD-H; Column Size: 3cm×25cm, 5μm; Injection: 2mL; Mobile phase: Hex: EtOH (0.1% FA) = 85:15; Flow rate: 36mL / min; Wavelength: UV 220nm; Temperature: 25℃; Sample solution: 25mg / mL in Hex / EtOH; Run time: 35mins) was separated and concentrated to obtain compound 1-17 (200mg, Rt = 24.86min, 100% ee, purity 98.5%, [α] D 20 = +16.83° (c 0.102, DMF)) and compound 1-18 (208 mg, Rt = 27.23 min, 100% ee, purity 99.1%, [α] D 20 = -19.58° (c 0.104, DMF).

[0295] Examples 1-20 and 1-21

[0296] Compound 1-19 (70 mg, 99% purity) was purified by chiral HPLC (Column: AD-H; Column Size: 3 cm × 25 cm, 5 μm; Injection: 4.5 mL; Mobile phase: Hex: EtOH (0.1% FA) = 85:15; Flow rate: 36 mL / min; Wavelength: UV 220 nm; Temperature: 25 ° C; Sample solution: 4 mg / mL in Hex / EtOH; Run time: 65 mins) was separated and concentrated to give compound 1-20 (32 mg, Rt = 59.4 min, 100% ee, purity 99.9%, [α] D 20 = +60.17° (c 0.103, DMF)) and compound 1-21 (32 mg, Rt = 45.8 min, 100% ee, purity 99.2%, [α] D 20 = -67.37° (c 0.100, DMF).

[0297] Examples 1-22 and 1-23

[0298] Compound 1-19 (70 mg, 97% purity) was purified by chiral HPLC (Column: AD-H; Column Size: 3 cm × 25 cm, 5 μm; Injection: 4.5 mL; Mobile phase: Hex: EtOH (0.1% FA) = 65:35; Flow rate: 26 mL / min; Wavelength: UV 220 nm; Temperature: 25 ° C; Sample solution: 4 mg / mL in Hex / EtOH; Run time: 30 mins) was separated and concentrated to obtain compound 1-22 (30 mg, Rt = 23.1 min, 100% ee, purity 100%, [α] D 20 = +59.65° (c 0.103, DMF)) and compound 1-23 (30 mg, Rt = 14.2 min, 100% ee, purity 99.9%, [α] D 20 =-65.81° (c 0.101, DMF).

[0299] Examples 1-25 and 1-26

[0300] Compound 1-24 (110 mg, 97% purity) was purified by chiral HPLC (Column: AD-H; Column Size: 3cm×25cm, 5μm; Injection: 4mL; Mobile phase: Hex: EtOH = 85:15; Flowrate: 30mL / min; Wavelength: UV 220nm; Temperature: 25℃; Sample solution: 7mg / mL in Hex / EtOH; Run time: 75mins) was separated and concentrated to obtain compound 1-25 (50mg, Rt = 61.8min, 100% ee, purity 99.7%, [α] D 20 = +1.95° (c 0.102, DMF)) and compound 1-26 (52 mg, Rt = 55.5 min, 100% ee, purity 99.4%, [α] D 20 =-2.62° (c 0.107, DMF)).

[0301] Example 1-92

[0302] 2-Chloro-N-(1-ethyl-1H-tetrazol-5-yl)-3-isopropylthio-4-methylsulfonylbenzamide

[0303]

[0304] At room temperature, intermediate 5 (500 mg, 1.62 mmol), 1-ethyl-5-aminotetrazolyl (183.17 mg, 1.62 mmol), pyridine (8 mL) and N-methylimidazole (465.56 mg, 5.67 mmol) were added to a 50 mL single-mouth bottle, cooled to 5 ° C in an ice bath, and oxalyl chloride (98.75 mg, 0.78 mmol) was slowly added dropwise. After the addition was completed, it was stirred at 0 ° C for 30 minutes, and then the reaction solution was heated to 55 ° C and stirred for 1 hour. After the reaction was completed, pyridine was removed by rotary evaporation, water was added to the reaction bottle, 5% dilute hydrochloric acid was added dropwise to adjust the pH value to 1-2, and 20 mL of ethyl acetate was extracted twice. After the organic phase was combined, it was washed once with saturated brine. Drying with anhydrous sodium sulfate, the solvent was evaporated under reduced pressure, and compound 1-92 (white solid, 470 mg) was obtained by silica gel column flash column chromatography.

[0305] 1 H NMR (400MHz, DMSO-d6) δ11.95(s,1H),8.18(d,J=8.1Hz,1H),8.00(d,J=8.2Hz,1H),4.45- 4.34(m,2H),3.88-3.74(m,1H),3.57(s,3H),1.49(t,J=7.2Hz,3H),1.25(t,J=5.9Hz,6H).

[0306] Example 1-93

[0307] 2-Chloro-N-(1-ethyl-1H-tetrazol-5-yl)-3-isopropylsulfinyl-4-methylsulfonylbenzamide

[0308]

[0309] At room temperature, compound 1-92 (260 mg, 0.513 mmol) and dichloromethane (6 mL) were added to a 25 mL single-mouth bottle, cooled to 5 ° C in an ice bath, and 85% m-chloroperbenzoic acid (124.99 mg, 0.616 mmol) was added in batches. After the addition was completed, the mixture was stirred in an ice bath for 1 hour. After the reaction was completed, solid impurities were filtered to remove the peroxides by washing with saturated sodium bisulfite, the solvent was evaporated under reduced pressure, and compound 1-93 (white solid, 180 mg) was obtained by silica gel column flash column chromatography.

[0310] 1H NMR (400MHz, DMSO-d6) δ11.99(s,1H),8.22(d,J=8.0Hz,1H),8.16(d,J=8.3Hz,1H),4.44 -4.32(m,2H),4.18-4.07(m,1H),3.53(s,3H),1.52-1.41(m,6H),1.12(d,J=7.0Hz,3H).

[0311] Example 1-96

[0312] 2-Chloro-N-(1-ethyl-1H-tetrazol-5-yl)-3-isopropylsulfonyl-4-methylsulfonylbenzamide

[0313]

[0314] At room temperature, intermediate 7 (250 mg, 0.73 mmol), 1-ethyl-5-aminotetrazole (82.98 mg, 0.73 mmol), pyridine (5 mL) and N-methylimidazole (210.94 mg, 2.57 mmol) were added to a 50 mL single-mouth bottle, cooled to 5 ° C in an ice bath, and oxalyl chloride (232.92 mg, 1.84 mmol) was slowly added dropwise. After the addition was completed, it was stirred at 0 ° C for 30 minutes, and then the reaction solution was heated to 55 ° C and stirred for 1 hour. After the reaction was completed, pyridine was removed by rotary evaporation, water was added to the reaction bottle, 5% dilute hydrochloric acid was added dropwise to adjust the pH value to 1-2, and 15 mL of ethyl acetate was extracted twice. After the organic phase was combined, it was washed once with saturated brine. Drying over anhydrous sodium sulfate, the solvent was evaporated under reduced pressure, and high-pressure reverse phase purification was obtained to obtain compound 1-96 (white solid, 189 mg).

[0315] 1 H NMR(400MHz,DMSO-d6)δ11.99(s,1H),8.48(d,J=8.2Hz,1H),8.34(d,1H),4.44-4.34 (m,2H),4.26-4.14(m,1H),3.64(s,3H),1.48(t,J=7.2Hz,3H),1.37(d,J=6.8Hz,6H).

[0316] Example 1-102

[0317] 2-Chloro-3-isopropylthio-N-methyl-N-(1-methyl-1H-tetrazol-5-yl)-4-methylsulfonylbenzamide

[0318]

[0319] At room temperature, intermediate 5 (1.50 g, 4.87 mmol) and N,N-dimethylformamide (13 mL) were added to a 50 mL single-mouth bottle, carbonyldiimidazole (1.58 g, 9.74 mmol) was added in batches, and the mixture was stirred at room temperature for 2 h. 1,8-diazacyclo[5,4,0]undecene-7 (2.52 g, 14.61 mmol) and N,1-dimethyl-1H-tetrazolyl-5-amine (1.00 g, 8.84 mmol) were added and stirred at room temperature for 2 hours. After the reaction was completed, the reactant was poured into 50 mL of ice water, the precipitated solid was filtered, washed with a small amount of water, the filter cake was dried, and the compound 1-102 (white solid, 1100 mg) was obtained by flash column chromatography on a silica gel column.

[0320] 1 H NMR (400 MHz, CDCl3-d, rotamer) δ 8.24 (d, J = 8.1 Hz, 0.7 H), 8.02 (d, J = 8.1 Hz, 0.3 H), 7.61 (d, J = 8.1 Hz, 0.7 H), 7.49 (d, J = 8.2 Hz, 0.3 H), 4.03-3.92 (m, 3 H), 3.86-3.75 (m, 0.7 H), 3.66-3.59 (m, 0.3 H), 3.46-3.39 (m, 3 H), 3.30 (s, 3 H), 1.27-1.23 (m, 4.2 H), 1.09 (d, J = 6.7 Hz, 1.8 H).

[0321] Example 1-103

[0322] 2-Chloro-3-isopropylsulfinyl-N-methyl-N-(1-methyl-1H-tetrazol-5-yl)-4-methylsulfonylbenzamide

[0323]

[0324] At room temperature, compound 1-102 (300 mg, 0.74 mmol) and dichloromethane (3 mL) were added to a 25 mL single-mouth bottle, and 85% m-chloroperbenzoic acid (151.13 mg, 0.74 mmol) was added in batches. After the addition was completed, the mixture was stirred for 1 hour. After the reaction was completed, solid impurities were removed by filtration, and peroxides were removed by washing with saturated sodium bisulfite. The solvent was evaporated under reduced pressure, and compound 1-103 (white solid, 201 mg) was obtained by silica gel column flash column chromatography.

[0325] 1H NMR (400 MHz, CDCl3-d, rotamer) δ 8.39-8.34 (m, 0.7H), 8.15 (d, J = 8.0 Hz, 0.3H), 7.81-7.69 (m, 1H), 4.40-3.89 (m, 4H), 3.60-3.24 (m, 6H), 1.71-0.98 (m, 6H).

[0326] Example 1-106

[0327] 2-Chloro-3-isopropylsulfonyl-N-methyl-N-(1-methyl-1H-tetrazol-5-yl)-4-methylsulfonylbenzamide

[0328]

[0329] At room temperature, compound 1-102 (305 mg, 0.76 mmol) and dichloromethane (3 mL) were added to a 25 mL single-mouth bottle, and 85% m-chloroperbenzoic acid (383.70 mg, 1.89 mmol) was added in batches. After the addition was completed, the mixture was stirred for 1 hour. After the reaction was completed, solid impurities were removed by filtration, and peroxides were removed by washing with saturated sodium bisulfite. The solvent was evaporated under reduced pressure, and compound 1-106 (white solid, 176 mg) was obtained by silica gel column flash column chromatography.

[0330] 1 H NMR (400 MHz, DMSO-d6, rotamer) δ 8.51 (d, J = 8.3 Hz, 0.5 H), 8.37 (d, J = 8.3 Hz, 0.5 H), 8.28 (d, J = 8.3 Hz, 0.5 H), 8.02 (d, J = 8.3 Hz, 0.5 H), 4.21 (p, J = 6.8 Hz, 0.5 H), 4.13-4.01 (m, 3.5 H), 3.63 (s, 1.5 H), 3.56 (s, 1.5 H), 3.46 (s, 1.5 H), 3.27 (s, 1.5 H), 1.39 (d, 3 H), 1.10-1.02 (m, 3 H).

[0331] Embodiment 2-6

[0332] 2-Chloro-3-(isopropylthio)-N-(1-methyl-1H-1,2,4-triazol-5-yl)-4-(methylsulfonyl)benzamide

[0333]

[0334] At room temperature, intermediate 5 (1.20 g, 3.88 mmol), 1-methyl-1H-1,2,4-triazole-5-amine (0.57 g, 5.83 mmol), N-methylimidazole (0.95 g, 11.64 mmol) and pyridine (15 mL) were added to a 100 mL single-mouth bottle, cooled to 0 ° C, thionyl chloride (1.38 g, 11.64 mmol) was added dropwise, and the mixture was moved to room temperature for overnight reaction. After the reaction was completed, pyridine was evaporated under reduced pressure, 10% hydrochloric acid (20 mL) was added to the system, and the aqueous phase was extracted with ethyl acetate (20 mL × 3). The organic phase was washed with water and saturated sodium chloride solution in turn, dried over anhydrous sodium sulfate, and the solvent was evaporated under reduced pressure. Silica gel column rapid column chromatography obtained compound 2-6 (yellow solid, 1.20 g)

[0335] 1 H NMR (400MHz, DMSO-d6) δ11.47(s,1H),8.16(d,J=7.9Hz,1H),8.01-7.87(m,2H),3.90-3.81(m,1H),3.80(s,3H),3.56(s,3H),1.26(d,J=6.5Hz,6H).

[0336] Embodiment 2-7

[0337] 2-Chloro-3-(isopropylsulfinyl)-N-(1-methyl-1H-1,2,4-triazol-5-yl)-4-(methylsulfonyl)amide

[0338]

[0339] At room temperature, compound 2-6 (200 mg, 0.51 mmol) and dichloromethane (5 mL) were added to a 25 mL single-mouth bottle, cooled to 5 ° C in an ice bath, and 85% m-chloroperbenzoic acid (94 mg, 0.46 mmol) was added in batches, and the mixture was moved to room temperature for 1 hour. After the reaction was completed, the solvent was removed in vacuo, and compound 2-7 (yellow solid, 90 mg) was obtained by reverse phase purification.

[0340] 1 H NMR (400MHz, DMSO-d6) δ11.53(s,1H),8.21(d,J=7.9Hz,1H),8.14(d,J=3.5Hz,1H),7.93(s,1 H),4.19-4.07(m,1H),3.80(s,3H),3.52(s,3H),1.46(d,J=6.7Hz,3H),1.12(d,J=6.8Hz,3H).

[0341] Examples 2-8 and 2-9

[0342] Compound 2-7 (120 mg, 99% purity) was purified by chiral HPLC (Column: AD-H; Column Size: 3 cm × 25 cm, 5 μm; Injection: 4 mL; Mobile phase: Hex: EtOH (0.1% FA) = 65:35; Flow rate: 43 mL / min; Wavelength: UV 220 nm; Temperature: 25 ° C; Sample solution: 5 mg / mL in Hex / EtOH; Run time: 30 mins) was separated and concentrated to obtain compound 2-8 (48 mg, Rt = 21.05 min, 100% ee, purity 100%, [α] D 20 = +56.09° (c 0.103, DMF)) and compound 2-9 (58 mg, Rt = 16.81 min, 100% ee, purity 100%, [α] D 20 = -58.03° (c 0.102, DMF).

[0343] Embodiment 2-10

[0344] 2-Chloro-3-(isopropylsulfonyl)-N-(1-methyl-1H-1,2,4-triazol-5-yl)-4-(methylsulfonyl)benzamide

[0345]

[0346] At room temperature, compound 2-6 (330 mg, 0.85 mmol) and dichloromethane (10 mL) were added to a 25 mL single-mouth bottle, cooled to 5 ° C in an ice bath, and 85% m-chloroperbenzoic acid (517 mg, 2.55 mmol) was added in batches, and the mixture was moved to room temperature for 1 hour. LC-MS monitored the reaction to be complete, the reaction was stopped, the solvent was removed in vacuo, and compound 2-10 (yellow solid, 130.mg) was obtained by reverse phase purification.

[0347] 1 H NMR (400MHz, DMSO-d6) δ11.59(s,1H),8.46(d,J=8.1Hz,1H),8.28(d,J=7.8Hz,1H) ,7.96(s,1H),4.28-4.12(m,1H),3.80(s,3H),3.63(s,3H),1.37(d,J=6.4Hz,6H).

[0348] Examples 2-29 and 2-30

[0349] Compound 2-28 (120 mg, 99% purity) was purified by chiral HPLC (Column: AD-H; Column Size: 3cm×25cm, 5μm; Injection: 4.5mL; Mobile phase: Hex:IPA (0.1% FA) = 75:25; Flow rate: 30mL / min; Wavelength: UV 220nm; Temperature: 25℃; Sample solution: 6mg / mL in Hex / EtOH / MeOH; Run time: 45mins) was separated and concentrated to obtain compound 2-29 (58mg, Rt = 27.83min, 100% ee, purity 98.6%, [α] D 20 = +99.87° (c 0.104, DMF)) and compound 2-30 (52 mg, Rt = 30.74 min, 100% ee, purity 99.1%, [α] D 20 = -98.32° (c 0.108, DMF)).

[0350] Example 2-82

[0351] 2-Chloro-3-(isopropylthio)-N-methyl-N-(1-methyl-1H-1,2,4-triazol-5-yl)-4-(methylsulfonyl)benzamide

[0352]

[0353] At room temperature, compound 2-6 (1.20 g, 3.08 mmol), N,N-dimethylformamide (10 mL) and anhydrous potassium carbonate (0.64 g, 4.62 mmol) were added to the single-mouth bottle in sequence, the reaction system was placed at 0°C, iodomethane (0.87 g, 6.16 mmol) was slowly added dropwise to the system, and stirred at 0°C for 30 minutes, and then the reaction system was moved to room temperature and stirred overnight. LC-MS monitored the reaction to be complete, the reaction was stopped, the reaction solution was added to water (50 mL), extracted with ethyl acetate three times, washed twice with saturated sodium chloride aqueous solution and dried with sodium sulfate, the solvent was removed in vacuo, and compound 2-82 (white solid, 0.8 g) was obtained by column chromatography purification.

[0354] 1H NMR (400 MHz, DMSO-d6, rotamer) δ 8.21 (d, J = 8.1 Hz, 0.3 H), 8.02-7.94 (m, 1.3 H), 7.67 (d, J = 8.7 Hz, 1.4 H), 3.82 (s, 2.1 H), 3.81-3.79 (m, 1.2 H), 3.70-3.64 (m, 0.7 H), 3.57 (s, 0.9 H), 3.47 (s, 2.1 H), 3.37 (s, 2.1 H), 3.16 (s, 0.9 H), 1.25 (d, J = 6.9 Hz, 1.8 H), 1.10 (d, J = 6.6 Hz, 4.2 H).

[0355] Example 2-83

[0356] 2-Chloro-3-(isopropylsulfinyl)-N-methyl-N-(1-methyl-1H-1,2,4-triazol-5-yl)-4-(methylsulfonyl)benzamide

[0357]

[0358] At room temperature, compound 2-82 (0.30 g, 0.74 mmol) and dichloromethane (5 mL) were added to a single-mouth bottle in sequence, the reaction system was placed at 0°C, 85% m-chloroperbenzoic acid (0.15 g, 0.74 mmol) was added in 3 batches, and the temperature was maintained at 0°C during this process. The reaction system was then moved to room temperature and stirred for 1 hour. LC-MS monitored the reaction to be complete, the reaction was stopped, the solvent was removed in vacuo, and compound 2-83 (white solid, 250 mg) was obtained by reverse phase purification.

[0359] 1 H NMR (400 MHz, DMSO-d6, rotamer) δ 8.24 (d, J = 8.1 Hz, 0.3 H), 8.16-7.98 (m, 1.3 H), 7.84 (d, J = 8.1 Hz, 0.7 H), 7.69 (s, 0.7 H), 4.15-4.04 (m, 0.3 H), 4.10-3.89 (s, 0.7 H), 3.84 (s, 2.1 H) ,3.81(s,0.9H),3.53(s,0.9H),3.46(s,2.1H),3.38(s,2.1H),3.20-3.19(s,0.9H),1. 46(d,J=6.8Hz,0.9H),1.40(d,J=6.8Hz,2.1H),1.14(s,0.9H),0.91(d,J=7.0Hz,2.1H).

[0360] Example 2-86

[0361] 2-Chloro-3-(isopropylsulfonyl)-N-methyl-N-(1-methyl-1H-1,2,4-triazol-5-yl)-4-(methylsulfonyl)benzamide

[0362]

[0363] At room temperature, compound 2-82 (0.30 g, 0.74 mmol) and dichloromethane (10 mL) were added to a single-mouth bottle in sequence, and 85% m-chloroperbenzoic acid (0.45 g, 2.22 mmol) was added to the system in batches, and stirred at room temperature for 1 hour. LC-MS monitored the reaction to be complete, the reaction was stopped, the solvent was removed in vacuo, and compound 2-86 (white solid, 250 mg) was obtained by reverse phase purification.

[0364] 1 H NMR (400 MHz, DMSO-d6, rotamer) δ 8.49 (d, J = 8.3 Hz, 0.3 H), 8.32-8.25 (m, 1 H), 8.02-7.97 (m, 1 H), 7.70 (s, 0.7 H), 4.26-4.14 (m, 0.3 H), 4.09-4.02 (m, 0.7 H), 3.85 (s, 2.1 H), 3.81 (s, 0.9 H), 3.63 (s, 0.9 H), 3.56 (s, 2.1 H), 3.39 (s, 2.1 H), 3.18 (s, 0.9 H), 1.38 (d, J = 6.9 Hz, 1.8 H), 1.24 (d, J = 6.6 Hz, 4.2 H).

[0365] Examples 3-3 and 3-4

[0366] Compound 3-2 (120 mg, 96% purity) was purified by chiral HPLC (Column: AD-H; Column Size: 3cm×25cm, 5μm; Injection: 4.5mL; Mobile phase: Hex: EtOH (0.1% FA) = 45:55; Flow rate: 20mL / min; Wavelength: UV 220nm; Temperature: 25℃; Sample solution: 6mg / mL in Hex / EtOH / MeOH; Run time: 100mins) was separated and concentrated to obtain compound 3-3 (52mg, Rt = 70.26min, 98.8%ee, purity 99.5%, [α] D 20= +98.84° (c 0.108, DMF)) and compound 3-4 (49 mg, Rt = 30.46 min, 100% ee, purity 99.6%, [α] D 20 = -101.09° (c 0.102, DMF)).

[0367] Embodiment 3-6

[0368] 2-Chloro-N-(5-methyl-1,3,4-oxadiazol-2-yl)-3-(isopropylthio)-4-(methylsulfonyl)benzamide

[0369]

[0370] At room temperature, intermediate 5 (510 mg, 1.65 mmol), 5-methyl-1,3,4-oxadiazole-2-amine (196.39 mg, 1.98 mmol), pyridine (8 mL) and N-methylimidazole (406.44 mg, 4.95 mmol) were added to a 100 mL single-mouth bottle, cooled to 5 ° C in an ice bath, and thionyl chloride (588.90 mg, 4.95 mmol) was slowly added dropwise. After the addition was completed, the mixture was stirred at room temperature for two hours. After the reaction was completed, 5% dilute hydrochloric acid was added dropwise to adjust the pH value to 1-2, and 15 mL of ethyl acetate was used for extraction twice. After the organic phase was combined, it was washed once with saturated brine. Drying with anhydrous sodium sulfate, the solvent was evaporated under reduced pressure, and compound 3-6 (white solid, 320 mg) was obtained by rapid column chromatography on a silica gel column.

[0371] 1 H NMR (400MHz, DMSO-d6) δ12.48(s,1H),8.14(d,J=8.1Hz,1H),7.87(d,J=8.2Hz ,1H),3.78(h,J=6.7Hz,1H),3.55(s,3H),2.48(s,3H),1.24(d,J=6.6Hz,6H).

[0372] Embodiment 3-7

[0373] 2-Chloro-3-(isopropylsulfinyl)-N-(5-methyl-1,3,4-oxadiazol-2-yl)-4-(methylsulfonyl)benzamide

[0374]

[0375] At room temperature, compound 3-6 (238 mg, 0.61 mmol) and dichloromethane (5 mL) were added to a 50 mL single-mouth bottle, cooled to 5 ° C in an ice bath, and 85% m-chloroperbenzoic acid (136.34 mg, 0.67 mmol) was added in batches. After the addition was completed, it was stirred at room temperature for 2 hours. After the reaction was completed, the solvent was evaporated under reduced pressure, and compound 3-7 (white solid, 83 mg) was obtained by silica gel column flash column chromatography.

[0376] 1 H NMR (400MHz, DMSO-d6) δ12.55(s,1H),8.18(d,J=8.1Hz,1H),8.05(d,J=8.1Hz,1H),4.2 3-3.93(m,1H),3.51(s,3H),2.48(s,3H),1.45(d,J=6.8Hz,3H),1.11(d,J=7.0Hz,3H).

[0377] Embodiment 3-10

[0378] 2-Chloro-3-(isopropylsulfonyl)-N-(5-methyl-1,3,4-oxadiazol-2-yl)-4-(methylsulfonyl)benzamide

[0379]

[0380] At room temperature, intermediate 7 (300 mg, 0.88 mmol), 5-methyl-1,3,4-oxadiazole-2-amine (104.69 mg, 1.06 mmol), pyridine (8 mL) and N-methylimidazole (217.59 mg, 2.65 mmol) were added to a 100 mL single-mouth bottle, cooled to 5 ° C in an ice bath, and thionyl chloride (315.27 mg, 2.65 mmol) was slowly added dropwise. After the addition was completed, the mixture was stirred at room temperature for two hours. After the reaction was completed, 5% dilute hydrochloric acid was added dropwise to adjust the pH value to 1-2, and 15 mL of ethyl acetate was used for extraction twice. After the organic phase was combined, it was washed once with saturated brine. Drying with anhydrous sodium sulfate, the solvent was evaporated under reduced pressure, and compound 3-10 (white solid, 216 mg) was obtained by rapid column chromatography on a silica gel column.

[0381] 1 H NMR (400MHz, DMSO-d6) δ12.55(s,1H),8.18(d,J=8.1Hz,1H),8.05(d,J=8.1Hz,1H),4.1 6-4.01(m,1H),3.51(s,3H),2.48(s,3H),1.45(d,J=6.8Hz,3H),1.11(d,J=7.0Hz,3H).

[0382] Examples 3-25 and 3-26

[0383] Compound 3-24 (65 mg, 96% purity) was purified by chiral HPLC (Column: AD-H; Column Size: 3cm×25cm, 5μm; Injection: 4mL; Mobile phase: Hex:EtOH=75:25; Flow rate: 36mL / min; Wavelength: UV 220nm; Temperature: 25℃; Sample solution: 8mg / mL in Hex / EtOH; Run time: 60mins) was separated and concentrated to obtain compound 3-25 (28mg, Rt=41.2min, 100%ee, purity 95.7%, [α] D 20 = +1.97° (c 0.102, DMF)) and compound 3-26 (30 mg, Rt = 30.7 min, 100% ee, purity 99.4%, [α] D 20 = -1.97° (c 0.102, DMF)).

[0384] Example 3-267

[0385] 2-Chloro-4-(methylsulfonyl)-N-(1,3,4-oxadiazol-2-yl)-3-(propylthio)benzamide

[0386]

[0387] At room temperature, intermediate 2 (300 mg, 0.97 mmol), 1,3,4-oxadiazole-2-amine (99.53 mg, 1.17 mmol), pyridine (6 mL) and N-methylimidazole (240.58 mg, 2.93 mmol) were added to a 100 mL single-mouth bottle, cooled to 5 ° C in an ice bath, and thionyl chloride (348.58 mg, 2.93 mmol) was slowly added dropwise. After the addition was completed, the mixture was stirred at room temperature for two hours. After the reaction was completed, 5% dilute hydrochloric acid was added dropwise to adjust the pH value to 1-2, and 15 mL of ethyl acetate was used for extraction twice. After the organic phase was combined, it was washed once with saturated brine. Drying with anhydrous sodium sulfate, the solvent was evaporated under reduced pressure, and compound 3-267 (white solid, 132 mg) was obtained by rapid column chromatography on a silica gel column.

[0388] 1H NMR (400MHz, DMSO-d6) δ12.60(s,1H),9.09(s,1H),8.14(d,J=8.1Hz,1H),7.91(d,J=8.1 Hz,1H),3.57(s,3H),2.99(t,J=7.4Hz,2H),1.64(h,J=7.4Hz,2H),0.99(t,J=7.3Hz,3H).

[0389] Example 3-268

[0390] 2-Chloro-4-(methylsulfonyl)-N-(1,3,4-oxadiazol-2-yl)-3-(propylsulfinyl)benzamide

[0391]

[0392] At room temperature, compound 3-267 (200 mg, 0.53 mmol) and dichloromethane (5 mL) were added to a 50 mL single-mouth bottle, cooled to 5 ° C in an ice bath, and 85% m-chloroperbenzoic acid (119.79 mg, 0.59 mmol) was added in batches. After the addition was completed, the mixture was stirred at room temperature for 2 hours. After the reaction was completed, the solvent was evaporated under reduced pressure, and compound 3-268 (white solid, 86 mg) was obtained by silica gel column flash column chromatography.

[0393] 1 H NMR (400MHz, DMSO-d6) δ12.69(s,1H),9.08(s,1H),8.12(d,J=8.1Hz,1H),8.05(d,J=8.1Hz,1H ),3.79-3.66(m,1H),3.54(s,3H),3.15-3.01(m,1H),1.90-1.73(m,2H),1.08(t,J=7.4Hz,3H).

[0394] Example 3-271

[0395] 2-Chloro-4-(methylsulfonyl)-N-(1,3,4-oxadiazol-2-yl)-3-(propanesulfonyl)benzamide

[0396]

[0397] At room temperature, intermediate 4 (300 mg, 0.88 mmol), 1,3,4-oxadiazole-2-amine (90.17 mg, 1.06 mmol), pyridine (8 mL) and N-methylimidazole (217.59 mg, 2.65 mmol) were added to a 100 mL single-mouth bottle, cooled to 5 ° C in an ice bath, and thionyl chloride (315.27 mg, 2.65 mmol) was slowly added dropwise. After the addition was completed, the mixture was stirred at room temperature for two hours. After the reaction was completed, 5% dilute hydrochloric acid was added dropwise to adjust the pH value to 1-2, and 15 mL of ethyl acetate was used for extraction twice. After the organic phase was combined, it was washed once with saturated brine. Drying with anhydrous sodium sulfate, the solvent was evaporated under reduced pressure, and compound 3-271 (white solid, 199 mg) was obtained by rapid column chromatography on a silica gel column.

[0398] 1 H NMR (400MHz, DMSO-d6) δ12.71(s,1H),9.09(s,1H),8.38(d,J=8.2Hz,1H),8.22(d,J= 8.2Hz,1H),3.71-3.66(m,2H),3.65(s,3H),1.95-1.84(m,2H),1.05(t,J=7.4Hz,3H).

[0399] Examples 3-283 and 3-284

[0400] Compound 3-282 (400 mg, 95% purity) was purified by chiral HPLC (Column: AD-H; Column Size: 3cm×25cm, 5μm; Injection: 4.5mL; Mobile phase: Hex:IPA (0.1% FA) = 90:10; Flow rate: 30mL / min; Wavelength: UV 220nm; Temperature: 25℃; Sample solution: 3mg / mL in Hex / EtOH; Run time: 45mins) was separated and concentrated to obtain compound 3-283 (198mg, Rt = 32.8min, 100% ee, purity 99.15%, [α] D 20 = +12.91° (c 0.115, DMF)) and compound 3-284 (183 mg, Rt = 36.8 min, 98.2% ee, purity 99.2%, [α] D 20 = -13.71° (c 0.108, DMF).

[0401] Examples 3-286 and 3-287

[0402] Compound 3-285 (220 mg, 99% purity) was purified by chiral HPLC (Column: AD-H; Column Size: 3cm×25cm, 5μm; Injection: 4.5mL; Mobile phase: Hex: EtOH (0.1% FA) = 75:25; Flow rate: 30mL / min; Wavelength: UV 220nm; Temperature: 25℃; Sample solution: 7mg / mL in Hex / EtOH; Run time: 45mins) was separated and concentrated to obtain compound 3-286 (100mg, Rt = 34.1min, 100% ee, purity 97.8%, [α] D 20 = +78.73° (c 0.105, DMF)) and compound 3-287 (101 mg, Rt = 25.3 min, 100% ee, purity 99.4%, [α] D 20 = -77.65° (c 0.109, DMF).

[0403] Examples 3-288 and 3-289

[0404] Compound 3-285 (160 mg, 99% purity) was purified by chiral HPLC (Column: AD-H; Column Size: 3cm×25cm, 5μm; Injection: 4.5mL; Mobile phase: Hex: EtOH (0.1% FA) = 75:25; Flow rate: 30mL / min; Wavelength: UV 220nm; Temperature: 25℃; Sample solution: 7mg / mL in Hex / EtOH; Run time: 50mins) was separated and concentrated to obtain compound 3-288 (72mg, Rt = 38.8min, 97.3% ee, purity 97.8%, [α] D 20 = +65.05° (c 0.104, DMF)) and compound 3-289 (74 mg, Rt = 22.3 min, 100% ee, purity 98.8%, [α] D 20 =-80.21° (c 0.105, DMF).

[0405] Example 3-388

[0406] 2-Chloro-N-(5-ethyl-1,3,4-oxadiazol-2-yl)-3-(isopropylthio)-4-(methylsulfonyl)benzamide

[0407]

[0408] At room temperature, intermediate 5 (300 mg, 0.97 mmol), 5-ethyl-1,3,4-oxadiazole-2-amine (131.88 mg, 1.17 mmol), pyridine (6 mL) and N-methylimidazole (240.58 mg, 2.93 mmol) were added to a 100 mL single-mouth bottle, cooled to 5 ° C in an ice bath, and thionyl chloride (348.58 mg, 2.93 mmol) was slowly added dropwise. After the addition was completed, the mixture was stirred at room temperature for two hours. After the reaction was completed, 5% dilute hydrochloric acid was added dropwise to adjust the pH value to 1-2, and 15 mL of ethyl acetate was used for extraction twice. After the organic phase was combined, it was washed once with saturated brine. Drying with anhydrous sodium sulfate, the solvent was evaporated under reduced pressure, and compound 3-388 (white solid, 228 mg) was obtained by rapid column chromatography on a silica gel column.

[0409] 1 H NMR (400MHz, DMSO-d6) δ12.52(s,1H),8.14(d,J=8.1Hz,1H),7.88(d,J=8.1H z,1H),3.85-3.75(m,1H),3.55(s,3H),2.91-2.77(m,2H),1.29-1.20(m,9H).

[0410] Example 3-389

[0411] 2-Chloro-N-(5-ethyl-1,3,4-oxadiazol-2-yl)-3-(isopropylsulfinyl)-4-(methylsulfonyl)benzamide

[0412]

[0413] At room temperature, compound 3-388 (200 mg, 0.50 mmol) and dichloromethane (5 mL) were added to a 50 mL single-mouth bottle, cooled to 5 ° C in an ice bath, and 85% m-chloroperbenzoic acid (109.64 mg, 0.54 mmol) was added in batches. After the addition was completed, the mixture was stirred at room temperature for 2 hours. After the reaction was completed, the solvent was evaporated under reduced pressure, and compound 3-389 (white solid, 115 mg) was obtained by silica gel column flash column chromatography.

[0414] 1H NMR (400MHz, DMSO-d6) δ12.58(s,1H),8.18(d,J=8.1Hz,1H),8.05(d,J=8.1Hz,1H),4.16-4.00(m,1H) ,3.51(s,3H),2.92-2.77(m,2H),1.45(d,J=6.8Hz,3H),1.25(t,J=7.5Hz,3H),1.11(d,J=7.0Hz,3H).

[0415] Example 3-392

[0416] 2-Chloro-N-(5-ethyl-1,3,4-oxadiazol-2-yl)-3-(isopropylsulfonyl)-4-(methylsulfonyl)benzamide

[0417]

[0418] At room temperature, intermediate 7 (300 mg, 0.88 mmol), 5-ethyl-1,3,4-oxadiazole-2-amine (118.86 mg, 1.06 mmol), pyridine (8 mL) and N-methylimidazole (217.59 mg, 2.65 mmol) were added to a 100 mL single-mouth bottle, cooled to 5 ° C in an ice bath, and thionyl chloride (315.27 mg, 2.65 mmol) was slowly added dropwise. After the addition was completed, the mixture was stirred at room temperature for two hours. After the reaction was completed, 5% dilute hydrochloric acid was added dropwise to adjust the pH value to 1-2, and 15 mL of ethyl acetate was used for extraction twice. After the organic phase was combined, it was washed once with saturated brine. Drying with anhydrous sodium sulfate, the solvent was evaporated under reduced pressure, and compound 3-392 (white solid, 189 mg) was obtained by rapid column chromatography on a silica gel column.

[0419] 1 H NMR (400MHz, DMSO-d6) δ8.42(d,J=8.2Hz,1H),8.16(d,J=8.3Hz,1H),4.25-4.11(m,1 H), 3.62 (s, 3H), 2.82 (q, J = 7.5Hz, 2H), 1.35 (d, J = 6.8Hz, 6H), 1.25 (t, J = 7.5Hz, 3H).

[0420] Examples 3-441 and 3-442

[0421] Compound 3-440 (100 mg, 98% purity) was purified by chiral HPLC (Column: AD-H; Column Size: 3cm×25cm, 5μm; Injection: 4.5mL; Mobile phase: Hex: EtOH (0.1% FA) = 35:65; Flow rate: 20mL / min; Wavelength: UV 220nm; Temperature: 25℃; Sample solution: 7mg / mL in Hex / EtOH / MeOH; Run time: 70mins) was separated and concentrated to obtain compound 3-441 (43mg, Rt = 49.44min, 97.6% ee, purity 97.5%, [α] D 20 = +64.66° (c 0.126, DMF)) and compound 3-442 (43 mg, Rt = 19.91 min, 100% ee, purity 99.8%, [α] D 20 = -67.30° (c 0.106, DMF)).

[0422] Example 3-499

[0423] 2-Chloro-N-(5-isopropyl-1,3,4-oxadiazol-2-yl)-4-(methylsulfonyl)-3-(propylthio)benzamide

[0424]

[0425] At room temperature, intermediate 2 (300 mg, 0.97 mmol), 5-isopropyl-1,3,4-oxadiazole-2-amine (148.77 mg, 1.17 mmol), pyridine (6 mL) and N-methylimidazole (240.58 mg, 2.93 mmol) were added to a 100 mL single-mouth bottle, cooled to 5 ° C in an ice bath, and thionyl chloride (348.58 mg, 2.93 mmol) was slowly added dropwise. After the addition was completed, the mixture was stirred at room temperature for two hours. After the reaction was completed, 5% dilute hydrochloric acid was added dropwise to adjust the pH value to 1-2, and 15 mL of ethyl acetate was used for extraction twice. After the organic phase was combined, it was washed once with saturated brine. Drying with anhydrous sodium sulfate, the solvent was evaporated under reduced pressure, and compound 3-499 (white solid, 219 mg) was obtained by silica gel column rapid column chromatography.

[0426] 1H NMR (400MHz, CDCl3-d) δ8.18(d,J=8.2Hz,1H),7.74(d,J=8.1Hz,1H),3.47(s,3H),3.22-3.07( m,1H),2.99(t,J=7.5Hz,2H),1.78-1.65(m,2H),1.39(d,J=7.0Hz,6H),1.03(t,J=7.4Hz,3H).

[0427] Example 3-500

[0428] 2-Chloro-N-(5-isopropyl-1,3,4-oxadiazol-2-yl)-4-(methylsulfonyl)-3-(propylsulfinyl)benzamide

[0429]

[0430] At room temperature, compound 3-499 (200 mg, 0.48 mmol) and dichloromethane (5 mL) were added to a 50 mL single-mouth bottle, cooled to 5 ° C in an ice bath, and 85% m-chloroperbenzoic acid (107.61 mg, 0.53 mmol) was added in batches. After the addition was completed, the mixture was stirred at room temperature for 2 hours. After the reaction was completed, the solvent was evaporated under reduced pressure, and compound 3-500 (white solid, 99 mg) was obtained by flash column chromatography on a silica gel column.

[0431] 1 H NMR (400MHz, CDCl3-d) δ8.17(d,J=8.1Hz,1H),7.88(d,J=8.1Hz,1H),3.97-3.86(m,1H),3.4 4(s,3H),3.21-3.04(m,2H),2.16-1.87(m,2H),1.40(d,J=7.0Hz,6H),1.16(t,J=7.4Hz,3H).

[0432] Example 3-503

[0433] 2-Chloro-N-(5-isopropyl-1,3,4-oxadiazol-2-yl)-4-(methylsulfonyl)-3-(propylsulfonyl)benzamide

[0434]

[0435] At room temperature, intermediate 4 (300 mg, 0.88 mmol), 5-isopropyl-1,3,4-oxadiazole-2-amine (134.78 mg, 1.06 mmol), pyridine (8 mL) and N-methylimidazole (217.59 mg, 2.65 mmol) were added to a 100 mL single-mouth bottle, cooled to 5 ° C in an ice bath, and thionyl chloride (315.27 mg, 2.65 mmol) was slowly added dropwise. After the addition was completed, the mixture was stirred at room temperature for two hours. After the reaction was completed, 5% dilute hydrochloric acid was added dropwise to adjust the pH value to 1-2, and 15 mL of ethyl acetate was used for extraction twice. After the organic phase was combined, it was washed once with saturated brine. Drying with anhydrous sodium sulfate, the solvent was evaporated under reduced pressure, and compound 3-503 (white solid, 212 mg) was obtained by rapid column chromatography on a silica gel column.

[0436] 1 H NMR(400MHz, CDCl3-d)δ8.39(d,J=8.2Hz,1H),7.94(d,J=8.2Hz,1H),3.67-3.57(m,5H ),3.22-3.07(m,1H),2.14-2.02(m,2H),1.41(d,J=7.0Hz,6H),1.14(t,J=7.4Hz,3H).

[0437] Examples 3-542 and 3-543

[0438] Compound 3-541 (145 mg, 97% purity) was purified by chiral HPLC (Column: AD-H; Column Size: 3cm×25cm, 5μm; Injection: 4.5mL; Mobile phase: Hex: EtOH (0.1% FA) = 65:35; Flow rate: 43mL / min; Wavelength: UV 220nm; Temperature: 25℃; Sample solution: 4mg / mL in Hex / EtOH / MeOH; Run time: 35mins) was separated and concentrated to obtain compound 3-542 (75mg, Rt = 22.66min, 100% ee, purity 98.6%, [α] D 20 = +57.50° (c 0.102, DMF)) and compound 3-543 (60 mg, Rt = 15.27 min, 100% ee, purity 99.3%, [α] D 20 =-70.69° (c 0.101, DMF).

[0439] Example 3-620

[0440] 2-Chloro-N-(5-cyclopropyl-1,3,4-oxadiazol-2-yl)-3-(isopropylthio)-4-(methylsulfonyl)benzamide

[0441]

[0442] At room temperature, intermediate 5 (300 mg, 0.97 mmol), 5-cyclopropyl-1,3,4-oxadiazole-2-amine (146.40 mg, 1.17 mmol), pyridine (8 mL) and N-methylimidazole (240.58 mg, 2.93 mmol) were added to a 100 mL single-mouth bottle, cooled to 5 ° C in an ice bath, and thionyl chloride (348.58 mg, 2.93 mmol) was slowly added dropwise. After the addition was completed, the mixture was stirred at room temperature for two hours. After the reaction was completed, 5% dilute hydrochloric acid was added dropwise to adjust the pH value to 1-2, and 15 mL of ethyl acetate was used for extraction twice. After the organic phase was combined, it was washed once with saturated brine. Drying with anhydrous sodium sulfate, the solvent was evaporated under reduced pressure, and compound 3-620 (white solid, 189 mg) was obtained by rapid column chromatography on a silica gel column.

[0443] 1 H NMR (400MHz, DMSO-d6) δ12.45(s,1H),8.14(d,J=8.1Hz,1H),7.87(d,J=8.2Hz,1H),3.85-3.73(m, 1H),3.55(s,3H),2.30-2.13(m,1H),1.24(d,J=6.6Hz,6H),1.17-1.07(m,2H),1.05-0.90(m,2H).

[0444] Example 3-621

[0445] 2-Chloro-N-(5-cyclopropyl-1,3,4-oxadiazol-2-yl)-3-(isopropylsulfinyl)-4-(methylsulfonyl)benzamide

[0446]

[0447] At room temperature, compound 3-620 (150 mg, 0.36 mmol) and dichloromethane (5 mL) were added to a 50 mL single-mouth bottle, cooled to 5 ° C in an ice bath, and 85% m-chloroperbenzoic acid (81.21 mg, 0.40 mmol) was added in batches. After the addition was completed, the mixture was stirred at room temperature for 2 hours. After the reaction was completed, the solvent was evaporated under reduced pressure, and compound 3-621 (white solid, 78 mg) was obtained by silica gel column flash column chromatography.

[0448] 1H NMR (400MHz, DMSO-d6) δ12.58(s,1H),8.17(d,J=8.1Hz,1H),8.02(d,J=8.2Hz,1H),4.15-4.02(m, 1H),3.51(s,3H),2.24-2.13(m,1H),1.45(d,J=6.8Hz,3H),1.16-1.03(m,5H),1.01-0.89(m,2H).

[0449] Examples 3-622 and 3-623

[0450] Compound 3-621 (120 mg, 99% purity) was purified by chiral HPLC (Column: AD-H; Column Size: 3cm×25cm, 5μm; Injection: 4mL; Mobile phase: Hex: EtOH (0.1% FA) = 65:35; Flow rate: 43mL / min; Wavelength: UV 220nm; Temperature: 25℃; Sample solution: 6mg / mL in Hex / EtOH; Run time: 30mins) was separated and concentrated to obtain compound 3-622 (61mg, Rt = 19.36min, 100% ee, purity 99.1%, [α] D 20 = +51.53° (c 0.111, DMF)) and compound 3-623 (52 mg, Rt = 13.89 min, 100% ee, purity 99.5%, [α] D 20 =-58.27° (c 0.101, DMF).

[0451] Example 3-624

[0452] 2-Chloro-N-(5-cyclopropyl-1,3,4-oxadiazol-2-yl)-3-(isopropylsulfonyl)-4-(methylsulfonyl)benzamide

[0453]

[0454] At room temperature, intermediate 7 (300 mg, 0.67 mmol), 5-cyclopropyl-1,3,4-oxadiazole-2-amine (100.60 mg, 0.80 mmol), pyridine (8 mL) and N-methylimidazole (197.06 mg, 2.40 mmol) were added to a 100 mL single-mouth bottle, cooled to 5 ° C in an ice bath, and thionyl chloride (285.53 mg, 2.40 mmol) was slowly added dropwise. After the addition was completed, the mixture was stirred at room temperature for two hours. After the reaction was completed, 5% dilute hydrochloric acid was added dropwise to adjust the pH value to 1-2, and 15 mL of ethyl acetate was used for extraction twice. After the organic phase was combined, it was washed once with saturated brine. Drying with anhydrous sodium sulfate, the solvent was evaporated under reduced pressure, and compound 3-624 (white solid, 163 mg) was obtained by silica gel column rapid column chromatography.

[0455] 1 H NMR (400MHz, DMSO-d6) δ12.58(s,1H),8.43(d,J=8.2Hz,1H),8.18(d,J=8.2Hz,1H),4.17(p,J=6.8H z,1H),3.62(s,3H),2.24-2.13(m,1H),1.35(d,J=6.8Hz,6H),1.15-1.04(m,2H),1.01-0.90(m,2H).

[0456] Example 3-786

[0457] 2-Chloro-N-methyl-N-(5-methyl-1,3,4-oxadiazol-2-yl)-4-(methylsulfonyl)-3-(propylthio)benzamide

[0458]

[0459] At room temperature, compound 3-2 (700 mg, 1.73 mmol), N,N-dimethylformamide (15 mL), potassium carbonate (479.59 mg, 3.47 mmol) were added to a 50 mL single-mouth bottle, cooled to 5 ° C in an ice bath, and iodomethane (731.79 mg, 5.19 mmol) was added dropwise. After the addition was completed, it was stirred at room temperature for 2 hours. After the reaction was completed, 5 mL of water was added, and 15 mL of ethyl acetate was extracted twice. After the organic phase was combined, it was washed once with saturated brine. Drying with anhydrous sodium sulfate, the solvent was evaporated under reduced pressure, and compound 3-786 (white solid, 433 mg) was obtained by silica gel column rapid column chromatography.

[0460] 1H NMR(400MHz, CDCl3-d)δ8.19(d,J=8.1Hz,1H),7.52(d,J=8.1Hz,1H),3.58(s,3H),3.4 5(s,3H),2.94(t,J=7.5Hz,2H),2.37(s,3H),1.73-1.61(m,2H),1.02(t,J=7.3Hz,3H).

[0461] Example 3-787

[0462] 2-Chloro-N-methyl-N-(5-methyl-1,3,4-oxadiazol-2-yl)-4-(methylsulfonyl)-3-(propylsulfinyl)benzamide

[0463]

[0464] At room temperature, compound 3-786 (150 mg, 0.37 mmol) and dichloromethane (5 mL) were added to a 50 mL single-mouth bottle, cooled to 5 ° C in an ice bath, and 85% m-chloroperbenzoic acid (83.24 mg, 0.41 mmol) was added in batches. After the addition was completed, the mixture was stirred at room temperature for 2 hours. After the reaction was completed, the solvent was evaporated under reduced pressure, and compound 3-787 (white solid, 126 mg) was obtained by silica gel column flash column chromatography.

[0465] 1 H NMR (400MHz, CDCl3-d) δ8.15(d,J=8.1Hz,1H),7.64(d,J=8.1Hz,1H),3.80-3.76(m,1H),3.58( s,3H),3.41(s,3H),3.11-2.99(m,1H),2.42(s,3H),2.07-1.83(m,2H),1.14(t,J=7.4Hz,3H).

[0466] Examples 3-788 and 3-789

[0467] Compound 3-787 (100 mg, 96% purity) was purified by chiral HPLC (Column: AD-H; Column Size: 3cm′25cm, 5mm; Injection: 4mL; Mobile phase: Hex: EtOH = 65:35; Flowrate: 43mL / min; Wavelength: UV 220nm; Temperature: 25℃; Sample solution: 4mg / mL in Hex / EtOH / MeOH; Run time: 40mins) was separated and concentrated to obtain compound 3-788 (46mg, Rt = 20.6min, 97.1% ee, purity 99.1%, [α] D 20 = +143.41° (c 0.099, DMF)) and compound 3-789 (46 mg, Rt = 30.1 min, 96.3% ee, purity 98.5%, [α] D 20 = -144.20° (c 0.097, DMF)).

[0468] Example 3-790

[0469] 2-Chloro-N-methyl-N-(5-methyl-1,3,4-oxadiazol-2-yl)-4-(methylsulfonyl)-3-(propylsulfonyl)benzamide

[0470]

[0471] At room temperature, compound 3-786 (150 mg, 0.37 mmol) and dichloromethane (5 mL) were added to a 50 mL single-mouth bottle, cooled to 5 ° C in an ice bath, and 85% m-chloroperbenzoic acid (225.37 mg, 1.11 mmol) was added in batches. After the addition was completed, the mixture was stirred at room temperature for 3 hours. After the reaction was completed, the solvent was evaporated under reduced pressure, and compound 3-790 (white solid, 49 mg) was obtained by silica gel column flash column chromatography.

[0472] 1 H NMR (400MHz, DMSO-d6) δ8.32(d,J=8.0Hz,1H),8.08(d,J=8.2Hz,1H),3.69-3. 60(m,5H),3.49(s,3H),2.33(s,3H),1.93-1.77(m,2H),1.02(t,J=7.4Hz,3H).

[0473] Example 4-1

[0474] 2-Chloro-N-(4-methyl-1,2,5-oxadiazol-3-yl)-4-(methylsulfonyl)-3-(propylthio)benzamide

[0475]

[0476] At room temperature, intermediate 2 (1.25 g, 4.06 mmol), pyridine (12 mL), 4-methyl-1,2,5-oxadiazole-3-amine (0.60 g, 6.09 mmol) and N-methylpyrazole (0.67 g, 8.12 mmol) were added to the single-mouth bottle in sequence, the reaction system was placed at 0 ° C, thionyl chloride (0.97 g, 8.12 mmol) was slowly added dropwise to the system, and stirred at 0 ° C for 30 minutes, and then the reaction system was moved to room temperature and stirred overnight. LC-MS monitored the reaction to be complete, the reaction was stopped, the solvent was removed in vacuo, 1M hydrochloric acid (50 mL) was added to the system, ethyl acetate was extracted three times, washed twice with saturated sodium chloride aqueous solution and dried with sodium sulfate, the solvent was removed in vacuo, and purified by silica gel column rapid column chromatography to obtain compound 4-1 (white solid, 610 mg).

[0477] 1 H NMR (400MHz, CDCl3-d) δ9.02(s,1H),7.91(d,J=8.1Hz,1H),7.61(d,J=8.2Hz,1H),3.37( s,3H),2.89(t,J=7.5Hz,2H),2.45(s,3H),1.64(h,J=7.4Hz,2H),0.98(t,J=7.4Hz,3H).

[0478] Example 4-2

[0479] 2-Chloro-N-(4-methyl-1,2,5-oxadiazol-3-yl)-4-(methylsulfonyl)-3-(propylsulfinyl)benzamide

[0480]

[0481] At room temperature, compound 4-1 (197 mg, 0.51 mmol) and dichloromethane (5 mL) were added to a single-mouth bottle in sequence, the reaction system was placed at 0°C, 85% m-chloroperbenzoic acid (104 mg, 0.51 mmol) was added in 3 batches, and the temperature was maintained at 0°C during this process. The reaction system was then moved to room temperature and stirred for 1 hour. LC-MS monitored the reaction to be complete, the reaction was stopped, the solvent was removed in vacuo, and compound 4-2 (white solid, 109 mg) was obtained by rapid column chromatography on a silica gel column.

[0482] 1H NMR (400MHz, CDCl3-d) δ9.61(s,1H),8.16(d,J=8.1Hz,1H),7.85(d,J=8.1Hz,1H),3.88-3.78( m,1H),3.41(s,3H),3.15-3.03(m,1H),2.51(s,3H),2.07-1.85(m,2H),1.15(t,J=7.4Hz,3H).

[0483] Examples 4-3 and 4-4

[0484] Compound 4-2 (130 mg, 98% purity) was purified by chiral HPLC (Column: AD-H; Column Size: 3cm×25cm, 5μm; Injection: 4mL; Mobile phase: Hex:EtOH=75:25; Flow rate: 43mL / min; Wavelength: UV 220nm; Temperature: 25℃; Sample solution: 5mg / mL in Hex / EtOH; Run time: 30mins) was separated and concentrated to obtain compound 4-3 (60mg, Rt=19.48min, 100%ee, purity 100%, [α] D 20 = +100.18° (c 0.108, DMF)) and compound 4-4 (58 mg, Rt = 12.69 min, 100% ee, purity 100%, [α] D 20 = -111.11° (c 0.121, DMF).

[0485] Embodiment 4-5

[0486] 2-Chloro-N-(4-methyl-1,2,5-oxadiazol-3-yl)-4-(methylsulfonyl)-3-(propylsulfonyl)benzamide

[0487]

[0488] At room temperature, compound 4-1 (313 mg, 0.80 mmol) and dichloromethane (10 mL) were added to the single-mouth bottle in turn, and 85% m-chloroperbenzoic acid (487 mg, 2.40 mmol) was added to the system in batches, and stirred at room temperature for 1 hour. LC-MS monitored the reaction to be complete, the reaction was stopped, the solvent was removed in vacuo, and the compound 4-5 (white solid, 128 mg) was purified by silica gel column flash column chromatography.

[0489] 1H NMR (400MHz, DMSO-d6) δ8.39(d,J=8.2Hz,1H),8.20(d,J=8.2Hz,1H),3.72-3.64(m,5H),2.40(s,3H),1.92(q,J=7.5Hz,2H),1.08(t,J=7.4Hz,3H).

[0490] Example 4-32

[0491] 2-Chloro-3-((cyclopropylmethyl)thio)-N-(4-methyl-1,2,5-oxadiazol-3-yl)-4-(methylsulfonyl)benzamide

[0492]

[0493] At room temperature, intermediate 20 (500 mg, 1.56 mmol), pyridine (8 mL), 4-methyl-1,2,5-oxadiazole-3-amine (232 mg, 2.34 mmol) and N-methylpyrazole (256 mg, 3.12 mmol) were added to the single-mouth bottle in sequence, the reaction system was placed at 0 ° C, thionyl chloride (371 mg, 3.12 mmol) was slowly added dropwise to the system, and stirred at 0 ° C for 30 minutes, and then the reaction system was moved to room temperature and stirred overnight. LC-MS monitored the reaction to be complete, the reaction was stopped, the solvent was removed in vacuo, 1M hydrochloric acid (50 mL) was added to the system, ethyl acetate was extracted three times, washed twice with saturated sodium chloride aqueous solution and dried with sodium sulfate, the solvent was removed in vacuo, and purified by silica gel column flash column chromatography to obtain compound 4-32 (white solid, 500 mg).

[0494] 1 H NMR (400MHz, CDCl3-d)) δ8.72(s,1H),8.08(d,J=8.1Hz,1H),7.72(d,J=8.0Hz,1H),3.49(s,3H) ,2.95(d,J=7.5Hz,2H),2.53(s,3H),1.09-1.0.5(m,1H),0.65-0.54(m,2H),0.33-0.21(m,2H).

[0495] Example 4-33

[0496] 2-Chloro-3-((cyclopropylmethyl)sulfinyl)-N-(4-methyl-1,2,5-oxadiazol-3-yl)-4-(methylsulfonyl)benzamide

[0497]

[0498] At room temperature, compound 4-32 (200 mg, 0.50 mmol) and dichloromethane (5 mL) were added to a single-mouth bottle in sequence, the reaction system was placed at 0°C, 85% m-chloroperbenzoic acid (102 mg, 0.50 mmol) was added in 3 batches, and the temperature was maintained at 0°C during this process. The reaction system was then moved to room temperature and stirred for 1 hour. LC-MS monitored the reaction to be complete, the reaction was stopped, the solvent was removed in vacuo, and compound 4-33 (brown-red solid, 120 mg) was obtained by rapid column chromatography on a silica gel column.

[0499] 1 H NMR (400MHz, CDCl3-d)) δ10.24(s,1H),8.07(d,J=8.1Hz,1H),7.83(d,J=8.1Hz,1H),3.96(dd,J=13.2,6.0Hz,1H),3 .40(s,3H),2.82(dd,J=13.2,9.1Hz,1H),2.45(s,3H),2.01(d,J=17.2Hz,2H),1.24-1.20(m,1H),0.82-0.68(m,2H).

[0500] Example 4-36

[0501] 2-Chloro-3-((cyclopropylmethyl)sulfonyl)-N-(4-methyl-1,2,5-oxadiazol-3-yl)-4-(methylsulfonyl)benzamide

[0502]

[0503] At room temperature, compound 4-32 (200 mg, 0.50 mmol) and dichloromethane (10 mL) were added to the single-mouth bottle in turn, and 85% m-chloroperbenzoic acid (305 mg, 1.50 mmol) was added to the system in batches, and stirred at room temperature for 1 hour. LC-MS monitored the reaction to be complete, the reaction was stopped, the solvent was removed in vacuo, and the compound 4-36 (white solid, 160 mg) was purified by silica gel column flash column chromatography.

[0504] 1 H NMR (400MHz, CDCl3-d) δ9.04(s,1H),8.32(d,J=8.1Hz,1H),7.93(d,J=8.2Hz,1H),3.60(s,2H),3.58(s,3H),2.50(s,3H),1.36 -1.19(m,1H),0.80-0.66(m,2H),0.52-0.37(m,2H).

[0505] Examples 4-44 and 4-45

[0506] Compound 4-43 (100 mg, 98% purity) was purified by chiral HPLC (Column: AD-H; Column Size: 3cm×25cm, 5μm; Injection: 4mL; Mobile phase: Hex: EtOH (0.1% FA) = 65:35; Flow rate: 43mL / min; Wavelength: UV 220nm; Temperature: 25℃; Sample solution: 6mg / mL in Hex / EtOH / MeOH; Run time: 20mins) was separated and concentrated to obtain compound 4-44 (40mg, Rt = 10.59min, 100% ee, purity 98.0%, [α] D 20 = +94.99° (c 0.099, DMF)) and compound 4-45 (48 mg, Rt = 7.52 min, 100% ee, purity 99.2%, [α] D 20 = -92.68° (c 0.108, DMF)).

[0507] Examples 4-49 and 4-50

[0508] Compound 4-48 (110 mg, 97% purity) was purified by chiral HPLC (Column: AD-H; Column Size: 3cm×25cm, 5μm; Injection: 4.5mL; Mobile phase: Hex: EtOH (0.1% FA) = 65:35; Flow rate: 26mL / min; Wavelength: UV 220nm; Temperature: 25℃; Sample solution: 6mg / mL in Hex / EtOH / MeOH; Run time: 30mins) was separated and concentrated to give compound 4-49 (54mg, Rt = 18.36min, 100% ee, purity 96%, [α] D 20 = +42.99° (c 0.100, DMF)) and compound 4-50 (49 mg, Rt = 11.70 min, 100% ee, purity 99.5%, [α] D 20 =-44.09° (c 0.104, DMF).

[0509] Example 4-271

[0510] 2-Chloro-N-methyl-N-(4-methyl-1,2,5-oxadiazol-3-yl)-4-(methylsulfonyl)-3-(propylthio)benzamide

[0511]

[0512] At room temperature, compound 4-1 (1.20 g, 3.08 mmol), N,N-dimethylformamide (10 mL) and anhydrous potassium carbonate (0.64 g, 4.62 mmol) were added to the single-mouth bottle in sequence, the reaction system was placed at 0°C, iodomethane (0.87 g, 6.16 mmol) was slowly added dropwise to the system, and stirred at 0°C for 30 minutes, and then the reaction system was moved to room temperature and stirred overnight. LC-MS monitored the reaction to be complete, the reaction was stopped, the reaction solution was added to water (50 mL), extracted three times with ethyl acetate, washed twice with saturated sodium chloride aqueous solution and dried with sodium sulfate, the solvent was removed in vacuo, and purified by silica gel column flash chromatography to obtain compound 4-271 (white solid, 0.8 g).

[0513] 1 H NMR (400 MHz, DMSO-d6, rotamer) δ 8.18 (d, J = 8.1 Hz, 0.5 H), 8.03-7.95 (m, 1 H), 7.74 (d, J = 8.2 Hz, 0.5 H), 3.57 (s, 1.5 H), 3.51 (s, 1.5 H), 3.44 (s, 1.5 H), 3.25 (s, 1.5 H), 3.02 (t, J = 7.4 Hz, 1 H), 2.91-2.77 (m, 1 H), 2.46 (s, 1.5 H), 2.41 (s, 1.5 H), 1.70-1.58 (m, 1 H), 1.51-1.33 (m, 1 H), 0.98 (t, J = 7.3 Hz, 1.5 H), 0.91 (t, J = 7.3 Hz, 1.5 H).

[0514] Example 4-272

[0515] 2-Chloro-N-methyl-N-(4-methyl-1,2,5-oxadiazol-3-yl)-4-(methylsulfonyl)-3-(propylsulfinyl)benzamide

[0516]

[0517] At room temperature, compound 4-271 (0.30 g, 0.74 mmol) and dichloromethane (5 mL) were added to a single-mouth bottle in sequence, the reaction system was placed at 0°C, and 85% m-chloroperbenzoic acid (0.15 g, 0.74 mmol) was added in three batches, and the temperature was maintained at 0°C during the process. The reaction system was then moved to room temperature and stirred for 1 hour. LC-MS monitored the reaction to be complete, the reaction was stopped, the solvent was removed in vacuo, and compound 4-272 (white solid, 250 mg) was obtained by flash chromatography on a silica gel column.

[0518] 1 H NMR (400 MHz, CDCl3-d, rotamer) δ8.18 (s, 0.6H), 8.01 (d, J = 8.2 Hz, 0.4H), 7.65 (d, J = 8.0 Hz, 0.6H), 7.56 (d, J = 8.1 Hz, 0.4H), 3.89-3.75 (m, 0.6H), 3.70-3.56 (m, 0.4H), 3.42 (s, 1.2H), 3.37 (s, 1.8H), 3. .31(s,1.8H),3.29(s,1.2H),3.14-3.01(m,0.6H),2.98-2.87(m,0.4H),2.39(s,1.8H),2.36(s,1 .2H),2.07-1.96(m,0.8H),1.90-1.76(m,1.2H),1.12(t,J=7.4Hz,1.8H),1.06(t,J=7.4Hz,1.2H).

[0519] Example 4-275

[0520] 2-Chloro-N-methyl-N-(4-methyl-1,2,5-oxadiazol-3-yl)-4-(methylsulfonyl)-3-(propylsulfonyl)benzamide

[0521]

[0522] At room temperature, compound 4-271 (0.30 g, 0.74 mmol) and dichloromethane (10 mL) were added to the single-mouth bottle in turn, and 85% m-chloroperbenzoic acid (0.45 g, 2.22 mmol) was added to the system in batches, and stirred at room temperature for 1 hour. LC-MS monitored the reaction to be complete, the reaction was stopped, the solvent was removed in vacuo, and the compound 4-275 (white solid, 250 mg) was purified by silica gel flash chromatography.

[0523] 1H NMR (400 MHz, CDCl3-d, rotamer) δ 8.48 (d, J = 8.2 Hz, 0.6 H), 8.31 (d, J = 8.2 Hz, 0.4 H), 7.83 (d, J = 8.2 Hz, 0.6 H), 7.74 (d, J = 8.2 Hz, 0.4 H), 3.67 (td, J = 7.2, 2.6 Hz, 2 H), 3.62 (s ,3H),3.56(s,2H),3.53(s,1H),3.49(s,2H),3.35(s,3H),2.46(s,3H),2.44(s,2H) ,2.15-2.10(m,1H),2.03-1.91(m,2H),1.17(t,J=7.4Hz,3H),1.11(t,J=7.4Hz,2H).

[0524] The preparation is carried out analogously to the preparation examples given above.

[0525] The analytical data of Example compounds 1-1 to 4-310 are shown in the following table

[0526] Table 2 Analysis data of compound of formula (I)

[0527]

[0528]

[0529]

[0530]

[0531]

[0532]

[0533]

[0534]

[0535]

[0536]

[0537]

[0538]

[0539]

[0540]

[0541]

[0542]

[0543]

[0544]

[0545]

[0546]

[0547]

[0548]

[0549]

[0550]

[0551]

[0552]

[0553]

[0554]

[0555]

[0556]

[0557]

[0558]

[0559]

[0560]

[0561]

[0562] Biological activity evaluation

[0563] Test Example 1: Indoor herbicidal activity determination

[0564] The herbicidal activity test method of the compounds of the present invention is as follows:

[0565] Before seedlings: sow a certain amount of grass weeds (barnyard grass, barnyard grass, rice barnyard grass, goosegrass, crabgrass, lycopodiella, foxtail grass, Japanese foxtail, sedge grass, sedge grass, perennial ryegrass, bluegrass, knotweed, wild oats, big-eared foxtail, brome), broadleaf weeds (channa oleracea, amaranth, wild rape, chickweed, veronica, cleaver, nightshade, cocklebur, sphagnum scabra, sesbania, wild arrowhead), and seeds of Cyperus rotundus, Cyperus rotundus, and Cyperus difformis in plastic pots with holes at the bottom of 7 cm in diameter and filled with nutrient soil; sow an appropriate amount of crop seeds (including indica rice, Seeds of japonica rice, glutinous rice, wheat, corn, sorghum, millet, soybean, cotton, rapeseed, and peanut were sown in plastic pots with a diameter of 10 cm and holes at the bottom and filled with nutrient soil. After sowing, the pots were covered with soil in an appropriate amount, and then the soil was soaked by absorbing water from the bottom. The pots were placed in a constant temperature and light culture room for 24 hours and then sprayed with a 3WP-2000 walking spray tower produced by the Nanjing Agricultural Mechanization Research Institute of the Ministry of Agriculture. The main shaft speed was 96 mm / r, the spray height was 300 mm, the effective spray width of the nozzle was 350 mm, and the spray area was 0.35 m 2 , the nozzle flow rate is 390mL / min; after the test materials are treated, they are placed in the laboratory and the liquid is naturally dried in the shade, and then placed in a constant temperature and light culture room for culture. The results are measured after 14-30 days depending on the situation. After seedlings: sow an appropriate amount of grass weeds (barnyard grass, barnyard grass, rice barnyard grass, goosegrass, crabgrass, lycopodiella, foxtail grass, Japanese alopecuroides, sedge grass, corytatum, alopecuroides, multiflora ryegrass, bluegrass, knotweed, wild oats, big-spiked alopecuroides, brome), broad-leaved weeds (channa d'arbus, amaranth, wild rape, chickweed, veronica, cleaver, nightshade, cocklebur, small fleabane, sesbania, wild arrowhead) and Cyperus rotundus, cyperus rotundus, cyperus diversiformis and other seeds on the diameter of Sow them in plastic pots with holes at the bottom of 7 cm in diameter and filled with nutrient soil; sow appropriate amount of crop seeds (including indica rice, japonica rice, glutinous rice, wheat, corn, sorghum, millet, soybean, cotton, rapeseed, peanut) in plastic pots with holes at the bottom of 10 cm in diameter and filled with nutrient soil, cover them with appropriate amount of soil after sowing, and then soak the soil by bottom water absorption, place them in a constant temperature and light culture room and culture them until the 3-6 leaf stage, and then spray them on the stems and leaves. After the test materials are treated, place them in the laboratory and wait for the liquid to dry naturally in the shade, then place them in a constant temperature and light culture room for culture, and measure the results after 14-21 days according to the situation.

[0566] Grading standards for pest control effects:

[0567] A means that the fresh weight inhibition rate is greater than or equal to 80% to 100%;

[0568] B means the fresh weight inhibition rate is greater than or equal to 60% and less than 80%;

[0569] C means the fresh weight inhibition rate is greater than or equal to 40% and less than 60%;

[0570] D means the fresh weight inhibition rate is greater than or equal to 20% and less than 40%;

[0571] E means that the fresh weight inhibition rate is less than 20%;

[0572] "NT" stands for not tested.

[0573] The test results show that the compound of the present invention has a 2 The control effect on the tested weeds was better at the doses given above. The representative data are shown in Table 3.

[0574] Table 3 Post-emergence weed test (150 g ai / hm 2 )

[0575]

[0576]

[0577]

[0578]

[0579]

[0580]

[0581]

[0582] Test Example 2: Indoor herbicidal activity and safety determination

[0583] According to the above test method, the compounds of the present invention were selected to compare their herbicidal activity and crop safety with the known compounds with the closest structures (CK1, CK2, CK3, CK4 are compounds 4-756, 4-759, 1-557, 1-563 listed in the specification of patent WO2012028579A1, CK5 is compound 290-1 listed in the specification of patent WO2013087577A1, and CK6 is compound 1-129 listed in the specification of patent WO2011035874A1). The results are shown in Tables 4 to 8.

[0584]

[0585] Table 4

[0586]

[0587] Table 5

[0588]

[0589] Table 6

[0590]

[0591]

[0592] Table 7

[0593]

[0594] Table 8

[0595]

[0596]

[0597] "NT" stands for not tested.

[0598] Test case 3: Field plot test

[0599] Field plot trials were conducted at the Zhuangxing Base of Shanghai Academy of Agricultural Sciences, Chonggu Experimental Base, Xinzhou City, Shanxi Province and other places.

[0600] 1. Experimental Methods

[0601] Stem and leaf spray: When the crop has 3 leaves and the weeds have 2 to 3 leaves, use the stem and leaf spray method to apply the pesticide once, with a water volume of 450 liters / hectare, and spray at a fixed time;

[0602] Broadcasting: 5 to 7 days after rice transplanting and when the rice plants are alive, apply the pesticide using the soil-moistened method. Mix 20 to 30 kg of moist fine soil (or fertilizer) per mu and spread evenly. When applying the pesticide, the water layer in the field should be 3 to 4 cm. Keep water for 5 to 7 days after applying the pesticide. After it dries up naturally, manage the slurry normally.

[0603] Measure wind speed and temperature during pesticide application and record weather conditions.

[0604] 2. Targets to be tested

[0605] Rice varieties: Huanghuazhan, Xiangzaoxian 45, Huaidao 5, Huiliangyousimiao, Nanjing 9108, Nanjing 46, Jinjing 616, Liannuo 1;

[0606] Sorghum varieties: red tassel;

[0607] Paddy field weeds: Echinochloa spp., Leptochloa chinensis, Amaranthus water spinulosa, Polygonum syringae, Cyperus difformis, Cyperus rotundus;

[0608] Weeds in dry fields: Echinochloa, Digitaria, Quinoa, Amaranthus, Solanum nigrum, and Purslane.

[0609] 3. Community Design

[0610] The experimental plots were randomly arranged with a plot area of ​​40 m2 and each treatment was repeated 4 times.

[0611] IV. Results Survey

[0612] 3-7 days after the application, visually inspect the symptoms of weed poisoning, and observe the damage or benefit of crops; 14 days after the application, visually inspect the weed control effect of each treatment, and visually inspect the recovery of crops in each treatment; 28 days after the application, inspect the number and fresh weight of weeds in each treatment, and collect rice plants in the previously observed damage area to measure plant height, root length, and fresh weight of aboveground and underground parts. A total of 3 surveys were conducted. In case of rainy days or other special circumstances, the survey time can be appropriately adjusted before or after.

[0613] 5. Data Processing

[0614] Calculation method of weed control effect and fresh weight control effect:

[0615] Plant control effect = (1-number of weeds in the treatment group / number of weeds in the control group) × 100%

[0616] Fresh weight control effect = (1-fresh weight of weeds in the treatment group / fresh weight of weeds in the control group) × 100%

[0617] The growth inhibition method was used to test safety. Based on the survey data, the average plant height, average aboveground fresh weight and inhibition rate of each treatment were calculated.

[0618] Calculation method for inhibition rate of rice plant height, root length, aboveground fresh weight and underground fresh weight:

[0619] Inhibition rate = (1-plant height or root length or aboveground fresh weight or underground fresh weight of rice in treatment group / plant height or root length or aboveground fresh weight or underground fresh weight of rice in control group) × 100%

[0620] The experimental results show that the compound of the present invention has good weed control effect and good crop safety.

[0621] Test Example 4: Algae toxicity evaluation experiment

[0622] (1) Test organisms: Pseudokirchneriella subcapitata, provided by the Freshwater Algae Species Bank of the Institute of Hydrobiology, Chinese Academy of Sciences.

[0623] (2) Test conditions: The test was carried out at a temperature of 21°C to 24°C, with continuous and uniform light intensity of 4440 to 8880 Lx.

[0624] BG11 medium was used for the culture and testing of Lunaea capillaris. The preparation method is shown in Table 9.

[0625] (3) Algae culture: Inoculate the algae for the test into a triangular flask containing BG11 culture medium according to the aseptic operation method, once every 96 hours, and repeat the inoculation 2 to 3 times until the algae basically reaches the synchronous growth stage, and use this as the algae for the test. Observe under a microscope each time you inoculate to check the growth of the algae.

[0626] (4) Preparation of drug solution: Weigh a certain amount of original drug using an electronic balance and fully dissolve it in an organic solvent such as DMSO or acetone to obtain a stock solution for later use.

[0627] (5) Preliminary test: According to the conditions of the formal test, set several groups of concentrations at relatively large intervals. Find the lowest concentration at which the test substance inhibits the growth of the test algae and the highest concentration at which it does not inhibit. Set the concentration of the formal test within this range.

[0628] (6) Formal test: According to the results of the preliminary test, five concentrations were set in a certain proportion. At the same time, BG11 medium was used as a blank control group, and BG11 medium containing organic solvents was used as a solvent control group. Under sterile conditions, the algae were cultured in 250 mL Erlenmeyer flasks. 50 mL of the corresponding concentration of drug solution was added to each bottle, and then a diluted concentration of 2.10×10 4 The initial concentration of algae in each treatment was 1.05×10 4 pcs / mL. After shaking, place in a light incubator for static culture, shaking once every 24 hours. Set up 3 parallels for each experimental group and control group. At 0h and 72h of the experiment, measure the temperature and pH value of each treatment concentration. Observe the growth of algae under a microscope at 24h, 48h, and 72h, and record the cell concentration with a hemocytometer.

[0629] (7) Toxicity evaluation: According to the national standard "Chemical Pesticide Environmental Safety Evaluation Test Guidelines - Part 14 Algal Growth Inhibition Test" (GB / T31270.14-2014), the toxicity of pesticides to algae is divided into three levels:

[0630] Highly toxic: EC 50 (72h)(mg ai / L)≤0.3

[0631] Poisoning: 0.3<EC 50 (72h)(mg ai / L)≤3.0

[0632] Low toxicity: EC 50 (72h)(mg ai / L)>3.0

[0633] Table 9 BG11 medium formula

[0634]

[0635] The test results show that most of the compounds of the present invention have low algae toxicity.

[0636] Test Example 5: Fish Toxicity Evaluation

[0637] (1) Materials and conditions

[0638] The fish used in the experiment are zebrafish (Brachydonio rerio), healthy and disease-free, with a size of 2-2.5 cm / tail. Before the experiment, they should be kept in the same environmental conditions as the experiment for 14 days, fed a small amount every day, and illuminated for 16 hours every day. Equipped with a complete fish tank filtration system. Stop feeding 24 hours before the experiment.

[0639] (2) Test water

[0640] The tap water was aerated for more than 24 hours using an air aeration pump. The test was conducted at a temperature of 21℃-25℃ and a light-dark ratio of 16h:8h. The water hardness was 10mg / L-250mg / L (calculated as CaCO3), pH 6.0-8.5, and the dissolved oxygen was not less than 60% of the air saturation value.

[0641] (3) Test method: static test method was used.

[0642] (4) Preparation of drug solution: Weigh a certain amount of original drug using an electronic balance and fully dissolve it in an organic solvent such as DMSO or acetone to obtain a stock solution for later use.

[0643] (5) Preliminary test: According to the conditions of the formal test, several groups of concentrations are set at large intervals. Five fish are used for each treatment, without replication, and the poisoning symptoms and deaths of the test fish are observed and recorded for 96 hours. The highest total survival concentration and the lowest total lethal concentration of the test fish are determined through the preliminary test, and the concentration of the formal test is set within this range.

[0644] (6) Formal test: According to the results of the preliminary test, five concentrations were set in a certain proportion, and a blank control group was set up. The pre-raised zebrafish were placed in the test tank. One parallel was set up for each treatment, and 500 ml of solution was added to each parallel, and 5 zebrafish were placed. At the beginning of the test, the temperature, pH value, and dissolved oxygen content ratio (dissolved oxygen in the test solution / air saturation value) of each treatment concentration and the blank control group were measured.

[0645] (7) Experimental observation and record: observe and record the poisoning symptoms and death number of zebrafish at 6h, 24h, 48h, 72h and 96h after exposure. Remove the dead fish immediately when they are found dead. The criterion for judging the death of zebrafish is that the fish has no visible movement, such as flapping gills and no response to touching the tail. The criterion for judging zebrafish poisoning is: the zebrafish has biological phenomena such as swimming sideways, lying on the bottom of the tank sideways or the body is obviously bent.

[0646] (8) Toxicity evaluation

[0647] According to the national standard "Chemical Pesticide Environmental Safety Evaluation Test Guidelines - Part 12 Fish Acute Toxicity Test" (GB / T31270.12-2014), the acute toxicity of pesticides to horsefish is divided into four levels:

[0648] Toxic: LC 50 (96h)(mg ai / L)≤0.1;

[0649] Highly toxic: 0.1<LC 50 (96h)(mg ai / L)≤1.0;

[0650] Poisoning: 1.0<LC 50 (96h)(mg ai / L)≤10;

[0651] Low toxicity: LC 50 (96h)(mg ai / L)>10.

[0652] The test results show that most of the compounds of the present invention have low fish toxicity.

[0653] The above is only a preferred embodiment of the present invention. It should be pointed out that a person skilled in the art can make several modifications and improvements without departing from the inventive concept of the present invention, which all belong to the protection scope of the present invention.

Claims

1. A 4-methylsulfonylbenzamide compound represented by general formula (I), a stereoisomer thereof or an agriculturally acceptable salt thereof: in: Q stands for Q1, Q2, Q3, or Q4, as shown below: X represents fluorine, chlorine or bromine; R1 represents C 3～6 Alkyl, C 3～6 Cycloalkyl, C 3～6 Cycloalkyl-C 1～6 Alkyl, halogenated C 1～6 Alkyl and not halogenated C1 alkyl, C 2～6 Alkenyl and not C2 alkenyl, C 2～6 Alkynyl and not C2 alkynyl or NC-C 1～6 alkyl; R2 represents hydrogen, C 1～6 Alkyl or RaO-C 1～6 alkyl; Rx represents hydrogen, C 1～6 Alkyl or C 3～7 Cycloalkyl; Ry represents hydrogen, C 1～6 Alkyl or C 3～6 Cycloalkyl; Rz represents hydrogen, C 1～6 Alkyl or C 3～7 Cycloalkyl; Ra stands for C 1～6 Alkyl; n represents 1 or 2; When n represents 1, the sulfur atom connected thereto can be selected from R type or S type, or a mixture of the two, and the ratio of R to S in the mixture is 1:99 to 99:

1.

2. The 4-methylsulfonylbenzamide compound according to claim 1, its stereoisomer or its agriculturally acceptable salt: in: Q stands for Q1, Q2, Q3, or Q4, as shown below: X stands for chlorine; R1 represents C 3～6 Alkyl, C 3～6 Cycloalkyl, C 3～6 Cycloalkylmethyl, haloC 3～4 Alkyl, C 2～4 Alkenyl and not C2 alkenyl, C 2～4 Alkynyl and not C2 alkynyl or NC-C 1～4 alkyl; R2 represents hydrogen, C 1～3 Alkyl or C 1～6 Alkyl-OC 1～6 alkyl; Rx represents hydrogen, C 1～3 Alkyl or cyclopropyl; Ry represents hydrogen, C 1～3 Alkyl or cyclopropyl; Rz represents hydrogen, C 1～3 Alkyl or cyclopropyl; n represents 1 or 2; When n represents 1, the sulfur atom connected thereto can be selected from R type or S type, or a mixture of the two, and the ratio of R to S in the mixture is 1:99 to 99:

1.

3. The 4-methylsulfonylbenzamide compound according to claim 2, its stereoisomer or its agriculturally acceptable salt: in: Q stands for Q1, Q2, Q3, or Q4, as shown below: X stands for chlorine; R1 represents CH2CH2CH3, CH(CH3)2, CH2CH2CH2CH3, CH(CH3)CH2CH3, cyclopropylmethyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, CH2CF3, CH2CH=CH2, CH2CH2Cl, CH2CH(CH3)2, C(CH3)3, CH2CH2CH2CH2CH3, CH(CH3)CH2CH2CH3, CH2CH2CH(CH3)2, C(CH3)2CH2CH3, CH2CH(CH3)CH2CH3, CH2CF2H, CH2CFH2, C(CH3)2CH ... CH2CH(CH3)2, CH2CH2CH3, CH2CH(CH3)CH2CH3, CH2CH(CH3)CH2CH3, CH2CF2H, CH2CFH2, CH2CH(CH3)2, CH2CH2CH3, CH2CH(CH3)CH2CH3, CH2CF2H, CH2CFH2, CH2CH(CH3)2, H(CH3)CH=CH2, (E)-CH2CH=CHCH3, (Z)-CH2CH=CHCH3, CH2CH=C(CH3)2, propargyl, but-3-en-2-yl, but-2-en-1-yl, CF2CF3, CF2CF2CF3, CH2CF2CF3, CH2CH2CF3, CH2CH2CF2H, CH2CH2CFH2, CF2CFHCF3, CH2CN, CH2CH2CN, CH(CH3)CN, CH(CH3)CH2CN, CHClCH3, CH2CF2H or CH2CFH2; R2 represents hydrogen, methyl, ethyl, CH(CH3)2 or C 1～6 Alkyl OC 1～6 alkyl; Rx represents hydrogen, methyl or ethyl; Ry represents: hydrogen, methyl, ethyl, isopropyl, cyclopropyl or CH2CH2CH3; Rz represents hydrogen, methyl, ethyl, isopropyl, cyclopropyl or CH2CH2CH3; n represents 1 or 2; When n represents 1, the sulfur atom connected thereto can be selected from R type or S type, or a mixture of the two, and the ratio of R to S in the mixture is 1:99 to 99:

1.

4. A method for preparing 4-methylsulfonylbenzamide compounds, stereoisomers thereof or agriculturally acceptable salts thereof according to any one of claims 1 to 3, characterized in that: The following steps are involved: (1) The compound represented by the general formula (VI) undergoes a substitution reaction with a differently substituted thiol or thiolate to generate a compound represented by the general formula (V); (2) the compound represented by the general formula (V) undergoes a condensation reaction with the compound represented by the general formula (IV) to generate a compound represented by the general formula (III); (3) The compound represented by the general formula (III) is subjected to an oxidation reaction to prepare the compound represented by the general formula (II); (4) The compound represented by the general formula (II) is subjected to a substitution reaction to obtain a 4-methylsulfonylbenzamide compound represented by the general formula (I); in: X1 is selected from fluorine or chlorine; R1, R2, X and Q are as described in any one of claims 1 to 3, and n represents 1 or 2.

5. A method for preparing the 4-methylsulfonylbenzamide compound, its stereoisomer or its agriculturally acceptable salt according to any one of claims 1 to 3, characterized in that: The following steps are involved: (1) the compound represented by the general formula (VI) undergoes a substitution reaction with a hydrogen sulfide to generate a thiophenol compound represented by the general formula (VII); (2) the compound represented by the general formula (VII) undergoes a substitution reaction with the compound represented by the general formula (VIII) to generate a compound represented by the general formula (V); (3) the compound represented by the general formula (V) undergoes a condensation reaction with the compound represented by the general formula (IV) to generate a compound represented by the general formula (III); (4) The compound represented by the general formula (III) is subjected to an oxidation reaction to prepare the compound represented by the general formula (II); (5) The compound represented by the general formula (II) is subjected to a substitution reaction to obtain a 4-methylsulfonylbenzamide compound represented by the general formula (I); in: X1 is selected from fluorine or chlorine; X2 is selected from chlorine, bromine, iodine, MsO (methylsulfonyloxy), TfO (trifluoromethylsulfonyloxy) or TsO (p-toluenesulfonyloxy); R1, R2, X and Q are as described in any one of claims 1 to 3.

6. A herbicidal composition, characterized in that: The composition comprises at least one of the 4-methylsulfonylbenzamide compounds, stereoisomers or agriculturally acceptable salts thereof as claimed in any one of claims 1 to 3, wherein the compound of formula (I) is used as the active ingredient, and the weight percentage of the active ingredient in the composition is 0.1-99.9%.

7. The herbicidal composition according to claim 6 further comprises a formulation adjuvant.

8. The herbicidal composition according to claim 7, comprising at least one further active compound selected from the group consisting of insecticides, acaricides, herbicides, fungicides, safeners and / or growth regulators.

9. The herbicidal composition according to claim 7 or 8, comprising a safener.

10. The herbicidal composition according to claim 9, wherein the safener is selected from mefenpyr-butyl, cyproconazole, isoxadiazine, cloquintocet-mexyl, fenthiocarb, fenthiocarb, fenthiocarb, dichloropropane or Metcamifen.

11. A method for controlling harmful plants, characterized in that: An effective amount of at least one compound of the formula (I) as claimed in any one of claims 1 to 3 or a herbicidal composition as claimed in any one of claims 6 is applied to the plants or the locus where the harmful plants grow.

12. Use of a compound of formula (I) according to any one of claims 1 to 3 or a herbicidal composition according to any one of claims 6 for controlling harmful plants.

13. The use according to claim 12, characterized in that The compounds of the formula (I) or herbicidal compositions comprising them are used for controlling harmful plants in crops of useful plants.

14. The use according to claim 13, wherein the useful plant crop is a transgenic crop or a crop treated with genome editing technology.

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