A sulfonamide-containing interdiamide derivative, a preparation method and application thereof

Abstract

The present application belongs to the technical field of pesticide chemistry, and provides a sulfonamide-containing inter-amide derivative, a preparation method and application thereof.The sulfonamide-containing inter-amide derivative has good insecticidal activity, and can effectively kill harmful insects such as Plutella xylostella and Ostrinia nubilalis.In addition, the preparation method of the sulfonamide-containing inter-amide derivative is simple, and has low cost, can be further developed as a new insecticide, and has potential application value; the LC 50 of the compound Ia-4 on zebra fish is 9.6 mg / L, belonging to the poisoning level; the LC 50 of the compounds Ia-2 and Ia-5 on zebra fish is 18.9 mg / L and 32.7 mg / L, respectively, belonging to the low toxicity level, is better than the poisoning level of brofenvalerate on zebra fish, belongs to the low risk level of aquatic organisms, and has low environmental risk.

Description

Technical Field

[0001] This invention relates to the field of pesticide chemistry, and in particular to a sulfonamide-containing metadiamide derivative, its preparation method, and its application. Background Technology

[0002] Pesticides are indispensable production materials for ensuring stable agricultural production and increased income, and are also very important strategic resources. In agricultural production, pesticides play a role in controlling crop diseases, pests, and weeds, regulating crop growth, and improving the quality and yield of agricultural products. The use of pesticides saves 70% of grain production, and insecticide sales account for 30% of total pesticide sales. Ionic γ-aminobutyric acid (GABA) receptors are an important insecticide target, and currently marketed insecticides that act on GABA receptors are all non-competitive antagonists of this receptor. GABA receptor insecticides were developed relatively early; since the mid-20th century, various GABA insecticides have been put into use and widely applied to the control of agricultural pests and disease-carrying insects, achieving significant control effects. Examples include traditional GABA receptor inhibitors such as cyclopentadienes, polychlorinated cycloalkanes, and phenylpyrazoles. New meta-diamide insecticides, such as brofenoxam, which were launched in 2020 and classified into the newly established Group 30 by IRAC, are gradually becoming a new research hotspot after neonicotinoids and o-diamides.

[0003] The emergence of pesticide resistance in pests often forces agricultural production to increase pesticide usage or application frequency. This not only further exacerbates the pressure of resistance screening, but more importantly, existing m-diamid insecticides generally have high acute toxicity to aquatic organisms. After application in the field, they can easily enter water bodies through surface runoff or drift, posing a high risk of exposure and ecological security hazards to non-target aquatic organisms such as fish and Daphnia. Therefore, structural modification of m-diamid compounds to reduce their toxicity to aquatic organisms and improve their environmental compatibility while maintaining insecticidal activity is an urgent need for the development of new green insecticides. Summary of the Invention

[0004] The purpose of this invention is to overcome the shortcomings of the prior art and provide a sulfonamide-containing meta-diamide derivative, its preparation method and application. The sulfonamide-containing meta-diamide derivative of this invention has both excellent insecticidal activity and low environmental risk.

[0005] To achieve the above objectives, the present invention is specifically implemented through the following technical solutions:

[0006] In a first aspect, the present invention provides a sulfonamide-m-diamide derivative, which is a compound of general formula I or its stereoisomers, polymorphs, isotopic derivatives, and pesticide-acceptable salts:

[0007]

[0008] General Formula I;

[0009] Wherein, R1 is an optionally substituted C1-C6 alkyl, C3-C6 cycloalkyl, optionally substituted aryl, or optionally substituted saturated alkyl.

[0010] And / or any of the unsaturated heterocyclic groups;

[0011] The substituents on R1 are selected from H, alkoxy, halogen, cyano, hydroxy, nitro, amino, mercapto, and optional substituents.

[0012] One or more of the following: alkyl, optionally substituted alkyloxy, optionally substituted alkylthio, or optionally substituted alkylamino;

[0013] The R2 is any one of H, C1-C6 alkyl, C1-C6 alkoxy, C1-C6 haloalkyl, C1-C6 cyanoalkyl, C1-C6 hydroxyalkyl, C1-C6 nitroalkyl, C1-C6 aminoalkyl, C1-C6 haloalkoxy-C1-C6 alkyl, C3-C6 cycloalkyl, and C3-C6 substituted cycloalkyl.

[0014] Secondly, the present invention also provides a method for preparing the aforementioned sulfonamide-containing meta-diamid derivative, wherein when R2 is H, the method for preparing the sulfonamide-containing meta-diamid derivative includes the following steps:

[0015] (a) Compound II-1: 2-(trifluoromethyl)aniline was mixed with heptafluoroisopropyliodine, a single-electron reducing agent, a phase transfer catalyst and solvent A to undergo an electrophilic substitution reaction to obtain compound II-2: 4-(heptafluoroisopropyl)-2-(trifluoromethyl)aniline.

[0016] (b) Compound II-3: 2-fluoro-3-nitrobenzoic acid was dispersed in an acyl chloride reagent and subjected to a nucleophilic addition-elimination reaction.

[0017] Compound II-4 was obtained: 2-fluoro-3-nitrobenzyl chloride;

[0018] (c) Compound II-4 and compound II-2 were dispersed in solvent B, and a catalyst and an acid-binding agent were added to obtain compound II-5: 2-fluoro-3-nitro-N-[4-(heptafluoroisopropyl)-2-(trifluoromethyl)phenyl]benzamide;

[0019] (d) Compound II-5, along with a base and sodium bromide, was dispersed in solvent C, and an oxidizing agent was added to obtain compound II-6: N-[2-bromo-4-(heptafluoroisopropyl)-6-(trifluoromethyl)phenyl]-2-fluoro-3-nitrobenzamide;

[0020] (e) Compound II-6 and the reducing agent were dispersed in solvent D, and acid was added to obtain compound II-7: 3-amino-N-[2-

[0021] [Bromo-4-(heptafluoroisopropyl)-6-(trifluoromethyl)phenyl]-2-fluorobenzamide;

[0022] (f) Compounds II-7 and II-8 are dispersed in solvent E, and a catalyst and an acid-binding agent are added to obtain the sulfonamide-containing meta-diamide derivative; wherein compound II-8 is... ;

[0023] When R2 is not H, the preparation method of the sulfonamide-containing meta-diamide derivative includes the following steps:

[0024] Compound II-7, 3-amino-N-[2-bromo-4-(heptafluoroisopropyl)-6-(trifluoromethyl)phenyl]-2-fluorobenzamide, was prepared according to steps (a) to (e) above.

[0025] (g) Compounds II-7 and II-9 are dispersed in solvent F, and acid is added to obtain compound II-10, wherein compound II-9 is R3CHO, and the structural formula of compound II-10 is [insert structural formula here]. In compound II-10, R2 is R3-CH2-;

[0026] (h) Disperse the compound II-10 and the compound II-8 in solvent E, and add a catalyst and an acid-binding agent to obtain the sulfonamide-containing meta-diamide derivative.

[0027] Thirdly, the present invention also provides the application of the aforementioned sulfonamide-containing metadiamide derivative in the preparation of pesticides for controlling pests.

[0028] Fourthly, the present invention also provides an insecticide comprising the aforementioned sulfonamide-containing metadiamide derivative and an agriculturally acceptable carrier.

[0029] Fifthly, the present invention also provides a method for controlling crop pests, by applying the aforementioned sulfonamide-containing metadiamide derivative or the aforementioned insecticide to the crop.

[0030] The sulfonamide-containing meta-diamid derivatives of the present invention have the following advantages compared with the prior art:

[0031] 1. The sulfonamide-containing m-diamid derivatives of the present invention have good insecticidal activity and can effectively kill harmful insects such as diamondback moth and corn borer. Furthermore, the preparation method of the sulfonamide-m-diamid derivatives of the present invention is simple and low-cost, and can be further developed into novel insecticides, possessing potential application value.

[0032] 2. Compounds Ia-1, Ia-2, Ia-4, Ia-5, Ib-4, and Ib-6 of this invention exhibit excellent insecticidal activity, with 24-hour lethality rates greater than 90% against diamondback moth and corn borer. Compounds Ia-2 and Ia-5 showed a 100% 24-hour lethality against third-instar diamondback moth and corn borer larvae. At 50 mg / L, all 12 compounds showed insecticidal activity against third-instar diamondback moth and corn borer larvae, but the overall insecticidal activity was slightly reduced. Compounds Ia-2, Ia-2, Ia-4, and Ia-5 showed a 24-hour lethality rate greater than 90% against diamondback moth; compounds Ia-2 and Ia-5 showed a 24-hour lethality rate greater than 90% against corn borer; compound Ia-4 showed a LC50% lethality rate against zebrafish. 50 The concentration was 9.6 mg / L, which falls into the category of poisoning (1.0 < LC50). 50 ≤ 10 mg / L); LC5 of compounds Ia-2 and Ia-5 on zebrafish 50 The concentrations were 18.9 mg / L and 32.7 mg / L, respectively, which fall into the low toxicity category (LC50). 50 >10 mg / L), which is generally better than the toxicity level of bromfenac in zebrafish (1.0 < LC). 50 (≤10 mg / L), which is classified as a low-risk level for aquatic organisms and has low environmental risk. Detailed Implementation

[0033] To make the objectives, technical solutions, and advantages of this invention clearer, the invention will be further described in detail below with reference to embodiments. The embodiments described herein are for illustrative purposes only and are not intended to limit the invention.

[0034] For ease of understanding, some terms are defined below. Unless otherwise specified, the meanings of the technical terms used in this invention are consistent with the meanings commonly understood by those skilled in the art to which this invention pertains.

[0035] Unless otherwise explicitly defined, all groups referred to in this invention have the following meanings:

[0036] "Alkyl" refers to a straight-chain or branched hydrocarbon group containing, for example, 1 to 8 carbon atoms (C1-C8) saturated, and composed only of carbon and hydrogen atoms. Examples include, but are not limited to: methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, n-pentyl, 2-methylbutyl, 2,2-dimethylpropyl, n-hexyl, heptyl, octyl, etc.

[0037] "Cycloalkyl" refers to a cyclic saturated hydrocarbon group containing 3, 4, 5, or more carbon atoms as ring atoms. In this invention, C3-C8 cycloalkyl refers to a ring containing 3-8 carbon atoms. Cycloalkyl groups include monocyclic, polycyclic (e.g., bicyclic), and fused ring systems. Examples include, but are not limited to: cyclopropyl, cyclobutyl, 1-methyl-cyclopropyl, 2-methyl-cyclopropyl, cyclopentyl, 1-methyl-cyclobutyl, 2-methyl-cyclobutyl, 3-methyl-cyclobutyl, 1,2-dimethyl-cyclopropyl, 2,3-dimethyl-cyclopropyl, 1-ethyl-cyclopropyl, 2-ethyl-cyclopropyl, cyclohexyl, 1-methyl-cyclopentyl, 2-methyl-cyclopentyl, 3-methyl-cyclopentyl, 1-ethyl-cyclobutyl, 2-ethyl-cyclobutyl, 3-ethyl-cyclobutyl, 1,2-dimethyl-cyclobutyl, 1,3-dimethyl-cyclobutyl Cyclobutyl, 2,2-dimethyl-cyclobutyl, 2,3-dimethyl-cyclobutyl, 2,4-dimethyl-cyclobutyl, 3,3-dimethyl-cyclobutyl, 1-n-propyl-cyclopropyl, 2-n-propyl-cyclopropyl, 1-isopropyl-cyclopropyl, 2-isopropyl-cyclopropyl, 1,2,2-trimethyl-cyclopropyl, 1,2,3-trimethyl-cyclopropyl, 2,2,3-trimethyl-cyclopropyl, 1-ethyl-2-methyl-cyclopropyl, 2-ethyl-1-methyl-cyclopropyl, 2-ethyl-2-methyl-cyclopropyl, cycloheptyl, cyclooctyl, etc.

[0038] "Aryl" refers to a group having a covalent π-electron system and at least one benzene ring, including monocyclic, polycyclic (such as bicyclic), and fused ring (rings sharing adjacent carbon pairs) systems, as well as fused cycloalkyl or heterocyclic alkyl groups as defined above with a benzene ring. Examples include, but are not limited to: phenyl, benzyl (or benzyl), xylyl, isopropylphenyl, naphthyl, anthracene, phenanthryl, fluorenyl, pyrrole, etc.

[0039] A "heterocyclic group" refers to a ring atom containing one or more heteroatoms (such as N, O, S) that are replaced by heteroatoms, while the remaining ring atoms are carbon atoms. It may optionally include double bonds. Examples include, but are not limited to: pyridine, pyridazine, pyrimidine, pyrazine, naphthalene, indole, oxazole, isoxazole, thiazole, isothiazole, furan, thiophene, pyrrole, triazole, piperazine, thiazole, morpholine, thiomorpholine, etc.

[0040] "Halogen" refers to elements selected from Group 17 of the periodic table, including but not limited to: fluorine, chlorine, bromine, and iodine.

[0041] The groups described above, such as alkyl, olefinic, and aryl groups, can be substituted or unsubstituted. In the case of "substituted," the hydrogen atoms on the group can be independently substituted by one or more substituents. When the number of substituents is two or more, the substituents can be the same or different. For example, "fluoromethyl" refers to a methyl group having one, two, or three fluorinated substituents, and "fluoroethyl" refers to an ethyl group having 1 to 5 fluorinated substituents.

[0042] This application provides a sulfonamide-containing metadiamide derivative, which is a compound as shown in general formula I or its stereochemical form.

[0043] Isomers, polymorphs, isotope derivatives, and pesticide-acceptable salts:

[0044]

[0045] General Formula I;

[0046] Wherein, R1 is any one of the following: optionally substituted C1-C6 alkyl, C3-C6 cycloalkyl, optionally substituted aryl, or optionally substituted saturated / unsaturated heterocyclic groups;

[0047] The substituents on R1 are selected from H, alkoxy, halogen, cyano, hydroxy, nitro, amino, mercapto, or optional substitutions.

[0048] One or more of the following: alkyl, optionally substituted alkyloxy, optionally substituted alkylthio, or optionally substituted alkylamino;

[0049] R2 is any one of H, C1-C6 alkyl, C1-C6 alkoxy, C1-C6 haloalkyl, C1-C6 cyanoalkyl, C1-C6 hydroxyalkyl, C1-C6 nitroalkyl, C1-C6 aminoalkyl, C1-C6 haloalkoxy-C1-C6 alkyl, C3-C6 cycloalkyl, and C3-C6 substituted cycloalkyl.

[0050] In some embodiments, R1 is any one of the optionally substituted C1-C3 alkyl, C3-C6 cycloalkyl, and optionally substituted aryl groups; the substituent on R1 is selected from any one of H, alkoxy, halogen, cyano, hydroxyl, nitro, optionally substituted alkyl, or optionally substituted alkyloxy groups; and R2 is any one of H, C1-C4 alkyl, C1-C4 cycloalkyl, C1-C4 alkoxy, C1-C4 cyanoalkyl, and C1-C4 aminoalkyl groups.

[0051] In some embodiments, R1 is any one of phenyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, pyridazinyl, pyrimidinyl, pyrazinyl, naphthyl, indolyl, oxazolyl, isoxazolyl, thiazolyl, isothiazolyl, furanyl, thiopheneyl, and pyrroleyl; the substituent on R1 is selected from any one of H, methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, methoxy, ethoxy, trifluoromethyl, trichloromethyl, halogen, and cyano; R2 is any one of H, C1-C4 alkyl, C1-C4 cycloalkyl, C1-C4 alkoxy, C1-C4 cyanoalkyl, and C1-C4 aminoalkyl; more preferably, R2 is any one of H, methyl, ethyl, cyclopropyl, methoxy, ethoxy, and cyano.

[0052] In some embodiments, R1 is any one of phenyl, o-fluorophenyl, m-fluorophenyl, p-fluorophenyl, p-chlorophenyl, p-bromophenyl, p-tolyl, and p-cyanophenyl; R2 is any one of H and methyl.

[0053] In some embodiments, the sulfonamide m-diamide derivative is selected from any one of the following formulas: Ia-1 to Ia-5 and Ib-1 to Ib-7.

[0054] .

[0055] Based on the same inventive concept, the present invention also provides a method for preparing the above-mentioned sulfonamide-containing meta-diamid derivative, wherein when R2 is H, the method for preparing the sulfonamide-containing meta-diamid derivative includes the following steps:

[0056] (a) Compound II-1: 2-(trifluoromethyl)aniline is mixed with heptafluoroisopropyl iodine, a single-electron reducing agent, a phase transfer catalyst, and solvent A to undergo an electrophilic substitution reaction, yielding compound II-2: 4-(heptafluoroisopropyl)-2-(trifluoromethyl)aniline, as shown in the following reaction formula:

[0057] ;

[0058] (b) Compound II-3: 2-fluoro-3-nitrobenzoic acid was dispersed in an acyl chloride reagent, with the selected acyl chloride reagent as the solvent. After a nucleophilic addition-elimination reaction, compound II-4: 2-fluoro-3-nitrobenzoyl chloride was obtained, as shown in the following reaction formula:

[0059] ;

[0060] (c) Compound II-4 and compound II-2 were dispersed in solvent B, and a catalyst and an acid-binding agent were added to obtain compound II-5: 2-fluoro-3-nitro-N-[4-(heptafluoroisopropyl)-2-(trifluoromethyl)phenyl]benzamide, as shown in the following reaction formula:

[0061] ;

[0062] (d) Compound II-5, along with a base and sodium bromide, was dispersed in solvent C. An oxidizing agent was added to obtain compound II-6: N-[2-bromo-4-(heptafluoroisopropyl)-6-(trifluoromethyl)phenyl]-2-fluoro-3-nitrobenzamide, as shown in the following reaction formula:

[0063] ;

[0064] (e) Compound II-6 and the reducing agent are dispersed in solvent D, and acid is added to obtain compound II-7: 3-amino-N-[2-bromo-4-(heptafluoroisopropyl)-6-(trifluoromethyl)phenyl]-2-fluorobenzamide, as shown in the following reaction formula:

[0065] ;

[0066] (f) Compounds II-7 and II-8 were dispersed in solvent E, and a catalyst and an acid-binding agent were added to obtain a sulfonamide-containing meta-diamid derivative; compound II-8 was... The reaction formula is as follows:

[0067] ;

[0068] Among them, compound Ia is the sulfonamide-containing meta-diamide derivative of the present invention (R2 is H).

[0069] When R2 is not H, the preparation method of the sulfonamide-containing meta-diamide derivative includes the following steps:

[0070] Compound II-7, 3-amino-N-[2-bromo-4-(heptafluoroisopropyl)-6-(trifluoromethyl)phenyl]-2-fluorobenzamide, was prepared according to steps (a) to (e) above.

[0071] (g) Compounds II-7 and II-9 are dispersed in solvent F, and acid is added to obtain compound II-10; wherein compound II-9 is R3CHO, and the structural formula of compound II-10 is [insert structural formula here]. In compound II-10, R2 is R3-CH2-, and the reaction formula is as follows:

[0072] ;

[0073] (h) Disperse compound II-10 and compound II-8 in solvent E, add a catalyst and an acid-binding agent to obtain a sulfonamide-containing meta-diamid derivative, as shown in the following reaction formula:

[0074] ;

[0075] Among them, compound Ib is the sulfonamide-containing meta-diamide derivative of the present invention (R2 is not H).

[0076] In some embodiments, in step (a), the molar ratio of 2-(trifluoromethyl)aniline, heptafluoroisopropyl iodine, single-electron reducing agent, and phase transfer catalyst is 1:(2.0~2.5):(2.5~3.0):(0.05~0.1); the single-electron reducing agent includes at least one of sodium dithionite, sodium ascorbate, sodium bisulfite, and sodium metabisulfite; further, the single-electron reducing agent may be a mixture of sodium bisulfite and sodium metabisulfite in a mass ratio of 1:1; the phase transfer catalyst includes tetrabutyl At least one of ammonium bromide, tetrabutylammonium chloride, hexadecyltrimethylammonium bromide, and tetrabutylammonium bisulfate; solvent A is any one of a mixture of ethyl acetate and water (volume ratio of ethyl acetate to water is 1.0:(0.5~1.5)), a mixture of methyl tert-butyl ether and water (volume ratio of methyl tert-butyl ether to water is 1.0:(0.5~1.5)), or a mixture of dichloromethane and water (volume ratio of dichloromethane to water is 1.0:(0.5~1.5)); the reaction temperature is 50~60 °C, and the reaction time is 4~6 h.

[0077] In some embodiments, in step (b), the acyl chloride reagent is one of thionyl chloride and oxalyl chloride, the solvent is the selected acyl chloride reagent, the reaction temperature is 80~90 °C, and the reaction time is 3~4 h.

[0078] In some embodiments, in step (c), the molar ratio of compound II-4, compound II-2, catalyst, and acid-binding agent is (1.1~1.2):1:(0.01~0.02):(1.2~1.5); the catalyst is any one of 4-dimethylaminopyridine and 4-pyrrolidinylpyridine; the acid-binding agent is any one of triethylamine, N,N-diisopropylethylamine, and pyridine; solvent B is any one of pyridine, 1,3-dichloropropane, toluene, and chlorobenzene; the reaction temperature is 100~110 °C, and the reaction time is 5~7 h.

[0079] In some embodiments, in step (d), the molar ratio of compound II-5, base, sodium bromide, and oxidizing agent is 1:1:(2.0~2.5):(2.5~3.0); the base is any one of sodium hydroxide and potassium hydroxide; the oxidizing agent is any one of sodium hypochlorite, sodium hypobromite, and hydrogen peroxide; the solvent C is any one of dichloromethane, 1,2-dichloroethane, and chloroform; the reaction temperature is 50~60 °C, and the reaction time is 5~6 h.

[0080] In some embodiments, in step (e), the molar ratio of compound II-6, reducing agent, and acid is 1:(2.0~2.5):(2.0~2.5); the reducing agent is any one of iron powder, zinc powder, tin powder, and stannous chloride; the acid is any one of hydrochloric acid and acetic acid; the solvent D is any one of methanol, ethanol, ethyl acetate, and dioxane; the reaction temperature is 60~80 °C, and the reaction time is 5~6 h.

[0081] In some embodiments, in step (f), the molar ratio of compound II-7, compound II-8, catalyst, and acid-binding agent is 1:(1.1~1.3):(0.05~0.10):(1.2~1.5); the catalyst is any one of 4-dimethylaminopyridine and 4-pyrrolidinylpyridine; the acid-binding agent is any one of triethylamine, pyridine, and N,N-diisopropylethylamine; the solvent E is any one of pyridine, dichloromethane, acetonitrile, tetrahydrofuran, and N,N-dimethylformamide; the reaction temperature is 40~60 °C, and the reaction time is 6~8 h.

[0082] In some embodiments, in step (g), the molar ratio of compound II-7, compound II-9, and acid is 1:(1.1~2.0):(1.2~2.5); the acid is either hydrochloric acid or sulfuric acid; the solvent F is either water or dioxane; the reaction temperature is 60~70 °C, and the reaction time is 5~6 h.

[0083] In some embodiments, in step (h), the molar ratio of compound II-10, compound II-8, catalyst, and acid-binding agent is 1:(1.1~1.3):(0.05~0.10):(1.2~1.5); the catalyst is any one of 4-dimethylaminopyridine and 4-pyrrolidinylpyridine; the acid-binding agent is any one of triethylamine, pyridine, and N,N-diisopropylethylamine; the solvent G is any one of pyridine, 1,3-dichloropropane, toluene, and chlorobenzene; the reaction temperature is 80~110 °C, and the reaction time is 12~20 h.

[0084] Based on the same inventive concept, this invention also provides the application of the above-mentioned sulfonamide-containing m-diamide derivatives in the preparation of pesticides for controlling pests. The pests mentioned above include at least one of the diamondback moth and the corn borer.

[0085] Based on the same inventive concept, the present invention also provides an insecticide comprising the above-mentioned sulfonamide-containing m-diamide derivative and an agriculturally acceptable carrier. The insecticide uses the sulfonamide-containing m-diamide derivative as the active component and can be dissolved or dispersed in the carrier to form a formulation for application, thereby improving the dispersibility and effectiveness of the insecticide.

[0086] Based on the same inventive concept, the present invention also provides a method for controlling crop pests by applying the above-mentioned sulfonamide-containing metadiamide derivatives or the above-mentioned insecticides to the crops.

[0087] The following specific embodiments further illustrate the sulfonamide-containing meta-diamide derivatives of the present invention, their preparation methods, and applications. This section further illustrates the content of the present invention in conjunction with specific embodiments, but should not be construed as limiting the present invention. Unless otherwise specified, the technical means used in the embodiments are conventional means well known to those skilled in the art. Unless otherwise specified, the reagents, methods, and equipment used in the present invention are conventional reagents, methods, and equipment in the art.

[0088] Example 1

[0089] This embodiment provides a sulfonamide-containing meta-diamide derivative, specifically N-[2-bromo-4-(heptafluoroisopropyl)-6-(trifluoromethyl)phenyl]-2-fluoro-3-(benzenesulfonamido)benzamide (Ia-1):

[0090] ;

[0091] The preparation of the above compound N-[2-bromo-4-(heptafluoroisopropyl)-6-(trifluoromethyl)phenyl]-2-fluoro-3-(benzenesulfonamido)benzamide (Ia-1) includes the following steps:

[0092] Step (a): Preparation of 4-(heptafluoroisopropyl)-2-(trifluoromethyl)aniline

[0093] In a 250 mL single-necked flask, 2-(trifluoromethyl)aniline (6.00 g, 37.24 mmol), heptafluoroisopropyl iodine (16.57 g, 74.48 mmol), and 80 mL of ethyl acetate were added sequentially. The mixture was stirred at room temperature (25 °C) to obtain an ethyl acetate solution, which was set aside. Separately, in a 250 mL beaker, sodium dithionite (16.21 g, 93.09 mmol), tetrabutylammonium bromide (0.60 g, 1.96 mmol), and 100 mL of water were added sequentially. After the sodium dithionite and tetrabutylammonium bromide were fully dissolved, the solution was transferred to a constant-pressure dropping funnel and added dropwise to the aforementioned ethyl acetate solution at 60 °C over a period of 2 hours. After the addition was complete, the reaction was allowed to proceed for 6 hours. After the reaction was complete, the mixture was allowed to stand and separated. The organic phase was collected and extracted twice with 50 mL of ethyl acetate. The combined organic phases were then subjected to 30 mL of ethyl acetate. After washing three times with mL of saturated saline solution, a small amount of anhydrous sodium sulfate was added and the mixture was dried for half an hour. The solution was then filtered, and the filtrate was concentrated under reduced pressure to obtain the crude product. This crude product was then purified by column chromatography (100-200 mesh) (eluent: pure petroleum ether) to obtain a reddish-brown liquid, which was 4-(heptafluoroisopropyl)-2-(trifluoromethyl)aniline, with a yield of 60.63%. 1H NMR spectrum:1 H NMR(400MHz, Chloroform-d) δ 7.67 (s, 2H), 7.49 (d, J = 8.7 Hz, 1H), 6.82 (s,1H), 6.83 (s, 1H);

[0094] Step (b): Preparation of 2-fluoro-3-nitrobenzoyl chloride

[0095] 2-fluoro-3-nitrobenzoic acid (5 g, 27.01 mmol) and 10 mL of thionyl chloride were added sequentially to a 100 mL single-necked flask. After reacting at room temperature for 4 hours, the reaction solution was distilled under pressure to remove excess thionyl chloride solvent, yielding a colorless liquid 2-fluoro-3-nitrobenzoyl chloride, which can be used directly in the next step without further processing.

[0096] Step (c): Preparation of 2-fluoro-3-nitro-N-[4-(heptafluoroisopropyl)-2-(trifluoromethyl)phenyl]benzamide

[0097] In a 100 mL two-necked flask, the intermediates 4-(heptafluoroisopropyl)-2-(trifluoromethyl)aniline (5.00 g, 15.19 mmol), 2-fluoro-3-nitrobenzyl chloride (3.40 g, 16.71 mmol), 4-dimethylaminopyridine (0.02 g, 0.15 mmol), triethylamine (2.64 mg, 18.23 mmol), and 15 mL of toluene were added sequentially, and the mixture was heated to 110 °C. o C. The reaction was carried out under reflux for 6 hours. After the reaction was complete, the reaction solution was extracted three times with 50 mL of EA (ethyl acetate), washed three times with 30 mL of saturated brine, dried for half an hour with a small amount of anhydrous sodium sulfate, filtered, and the filtrate was concentrated under reduced pressure to obtain the crude product. This crude product was then purified by column chromatography (100-200 mesh) (eluent: PE:EA = 10:1) to obtain a white powder, namely 2-fluoro-3-nitro-N-[4-(heptafluoroisopropyl)-2-(trifluoromethyl)phenyl]benzamide, with a yield of 78.05%. 1H NMR spectrum: 1 H NMR (400 MHz, DMSO-d6) δ 10.71 (s, 1H), 8.31 (ddd, J = 8.6, 7.2, 1.8 Hz, 1H), 8.14-8.08 (m,1H), 8.08-7.98 (m, 2H), 7.92 (d, J = 2.3 Hz, 1H), 7.62-7.54 (m, 1H).

[0098] Step (d): Preparation of N-[2-bromo-4-(heptafluoroisopropyl)-6-(trifluoromethyl)phenyl]-2-fluoro-3-nitrobenzamide

[0099] Add 2-fluoro-3-nitro-N-[4-(heptafluoroisopropyl)-2-(trifluoromethyl)phenyl]benzamide (5.00 g, 10.08 mmol), sodium hydroxide (0.40 g, 10.08 mmol), sodium bromide (2.07 g, 20.15 mmol), 10% sodium hypochlorite solution (2.25 g, 30.23 mmol), and 15 mL of dichloromethane to a 100 mL single-necked flask, and heat to 50 °C. o The reaction mixture was refluxed at C for 6 hours. After the reaction was complete, the reaction solution was extracted three times with 50 mL of EA, washed three times with 30 mL of saturated brine, dried for half an hour with a small amount of anhydrous sodium sulfate, filtered, and the filtrate was concentrated under reduced pressure to obtain the crude product. This crude product was then purified by column chromatography (100-200 mesh) (eluent: PE:EA = 20:1) to obtain a yellow powder, which is N-[2-bromo-4-(heptafluoroisopropyl)-6-(trifluoromethyl)phenyl]-2-fluoro-3-nitrobenzamide, with a yield of 94.76%. 1H NMR spectrum: 1 H NMR (400 MHz, DMSO-d6) δ 11.06 (s, 1H), 8.39 (s, 1H), 8.36-8.27 (m, 1H), 8.01 (ddd, J =7.7, 5.8, 1.8 Hz, 1H), 7.93 (d, J = 2.1 Hz, 1H), 7.59 (t, J = 8.0 Hz, 1H).

[0100] Step (e): Preparation of 3-amino-N-[2-bromo-4-(heptafluoroisopropyl)-6-(trifluoromethyl)phenyl]-2-fluorobenzamide

[0101] In a 100 mL single-necked flask, add N-[2-bromo-4-(heptafluoroisopropyl)-6-(trifluoromethyl)phenyl]-2-fluoro-3-nitrobenzamide (3.00 g, 5.22 mmol), stannous chloride (2.35 g, 10.43 mmol), 36% hydrochloric acid (1.12 mL, 13.04 mmol), and 15 mL of dioxane. Heat to 60°C. oThe reaction was carried out under reflux for 6 hours. After the reaction was complete, sodium hydroxide solution was added to the reaction solution to bring the pH close to 14. The liquid phase was obtained by filtration and extracted three times with 85 mL of EA. After washing three times with 30 mL of saturated brine, a small amount of anhydrous sodium sulfate was added and the solution was dried for half an hour. Rapid column chromatography was performed using a vacuum filtration funnel (eluent: PE:EA = 5:1) for separation and purification. The filtrate was concentrated under reduced pressure to obtain a white powder, which is 3-amino-N-[2-bromo-4-(heptafluoroisopropyl)-6-(trifluoromethyl)phenyl]-2-fluorobenzamide, with a yield of 96.66%. 1H NMR spectrum: 1 H NMR (400MHz, DMSO-d6) δ 10.49 (s, 1H), 8.41 (d, J = 2.2 Hz, 1H), 7.96 (d, J = 2.1 Hz,1H), 7.04-6.91 (m, 2H), 6.82 (ddd, J = 7.6, 5.8, 1.8 Hz, 1H), 5.42 (s, 2H);

[0102] Step (f): Preparation of N-(2-bromo-4-(perfluoroprop-2-yl)-6-(trifluoromethyl)phenyl)-2-fluoro-3-(benzenesulfonamide)benzamide

[0103] In a 100 mL single-necked flask, add 3-amino-N-[2-bromo-4-(heptafluoroisopropyl)-6-(trifluoromethyl)phenyl]-2-fluorobenzamide (200.00 mg, 366.87 µmol), benzenesulfonyl chloride (56.34 μL, 440.25 µmol), 4-dimethylaminopyridine (4.48 mg, 36.69 µmol), triethylamine (55.69 μL, 440.25 µmol), and 15 mL of pyridine. Heat to 50 °C. o The reaction mixture was refluxed at C for 6 hours. After the reaction was complete, the reaction solution was extracted three times with 50 mL of EA, washed three times with 30 mL of saturated brine, dried for half an hour with a small amount of anhydrous sodium sulfate, filtered, and the filtrate was concentrated under reduced pressure to obtain the crude product. This crude product was then purified by column chromatography (eluent was petroleum ether (PE) and ethyl acetate (EA) in a volume ratio of 8:1) to obtain a white powder, namely N-[2-bromo-4-(heptafluoroisopropyl)-6-(trifluoromethyl)phenyl]-2-fluoro-3-(benzenesulfonamide)benzamide (Ia-1), with a yield of 80.34%. Melting point: 155-158 °C; 1H NMR spectrum: 1H NMR (400 MHz, DMSO-d6) δ 10.74 (s, 1H),10.47 (s, 1H), 8.42 (d, J = 2.2 Hz, 1H), 7.95 (d, J = 2.2 Hz, 1H), 7.83 -7.77 (m, 2H), 7.70 - 7.64 (m, 1H), 7.63 - 7.56 (m, 2H), 7.49 - 7.42 (m, 2H),7.29 (t, J = 7.9 Hz, 1H); MS(ESI+), m / z ([M+H] + calcd for C 23 H 13 BrF 11 N2O3S684.9649, found 684.9641.

[0104] Example 2

[0105] This embodiment provides a sulfonamide-containing meta-diamide derivative, specifically N-(2-bromo-4-(perfluoroprop-2-yl)-6-(trifluoromethyl)phenyl)-2-fluoro-3-((4-methylphenyl)sulfonamide)benzamide (Ia-3):

[0106] ;

[0107] The preparation of the above compound N-(2-bromo-4-(perfluoroprop-2-yl)-6-(trifluoromethyl)phenyl)-2-fluoro-3-((4-methylphenyl)sulfonamide)benzamide (Ia-3) includes the following steps:

[0108] Steps (a) to (e) are the same as in Example 1;

[0109] Step (f): Preparation of N-(2-bromo-4-(perfluoroprop-2-yl)-6-(trifluoromethyl)phenyl)-2-fluoro-3-((4-methylphenyl)sulfonylamino)benzamide

[0110] Add 3-amino-N-[2-bromo-4-(heptafluoroisopropyl)-6-(trifluoromethyl)phenyl]-2-fluorobenzamide (200.00 mg, 366.87 µmol), 4-methylbenzenesulfonyl chloride (83.64 mg, 440.25 µmol), 4-dimethylaminopyridine (4.48 mg, 36.69 µmol), triethylamine (55.69 μL, 440.25 µmol), and 15 mL of pyridine to a 100 mL single-necked flask, and heat to 50 °C and reflux for 6 hours. After the reaction was complete, the reaction solution was extracted three times with 50 mL of EA, washed three times with 30 mL of saturated brine, dried for half an hour with a small amount of anhydrous sodium sulfate, filtered, and the filtrate was concentrated under reduced pressure to obtain the crude product. This crude product was then purified by column chromatography (eluent was petroleum ether (PE) and ethyl acetate (EA) in a volume ratio of 10:1) to obtain a white powder, which was the target compound Ia-3, with a yield of 75.38%. Melting point 149-152 °C; 1H NMR spectrum: 1 H NMR (400 MHz, DMSO-d6) δ 10.71 (s, 1H), 10.37 (s, 1H), 8.42 (d, J = 2.2 Hz, 1H), 7.95 (d, J =2.1 Hz, 1H), 7.71 – 7.64 (m, 2H), 7.48 – 7.42 (m, 2H), 7.38 (d, J = 8.0 Hz,2H), 7.29 (t, J = 7.9 Hz, 1H), 2.37 (s, 3H); MS(ESI+), m / z ([M+H] + ) calcd forC 24 H 15 BrF 11 N2O3S 698.9806, found 698.9799.

[0111] Example 3

[0112] This embodiment provides a sulfonamide-containing meta-diamide derivative, specifically N-[2-bromo-4-(heptafluoroisopropyl)-6-(trifluoromethyl)phenyl]-2-fluoro-3-(N-methylbenzenesulfonamido)benzamide (Ib-1):

[0113] ;

[0114] The preparation of the above compound N-[2-bromo-4-(heptafluoroisopropyl)-6-(trifluoromethyl)phenyl]-2-fluoro-3-(N-methylbenzenesulfonamido)benzamide (Ib-1) includes the following steps:

[0115] Steps (a) to (e) are the same as in Example 1;

[0116] Step (f): Preparation of N-(2-bromo-4-(perfluoroprop-2-yl)-6-(trifluoromethyl)phenyl)-2-fluoro-3-(methylamino)benzamide

[0117] 3-amino-N-[2-bromo-4-(heptafluoroisopropyl)-6-(trifluoromethyl)phenyl]-2-fluorobenzamide (200.00 mg, 366.87 µmol), 37% formaldehyde solution (33.08 μL, 440.25 µmol), and concentrated sulfuric acid (39.91 μL, 733.74 µmol) were added to a 100 mL single-necked flask. The mixture was heated to 60 °C and refluxed for 6 hours. After the reaction was complete, the reaction solution was extracted three times with 50 mL of EA, washed three times with 30 mL of saturated brine, dried for half an hour with a small amount of anhydrous sodium sulfate, filtered, and the filtrate was concentrated under reduced pressure to obtain the crude product. This crude product was then purified by column chromatography (eluent was petroleum ether (PE) and ethyl acetate (EA) in a volume ratio of 15:1) to obtain a pale yellow powder, namely N-(2-bromo-4-(perfluoroprop-2-yl)-6-(trifluoromethyl)phenyl)-2-fluoro-3-(methylamino)benzamide, with a yield of 86.90%. 1H NMR spectrum: 1 H NMR (400 MHz, DMSO-d6) δ 10.51 (s, 1H), 8.40 (d, J = 2.1 Hz, 1H), 8.00 - 7.91 (m, 1H), 7.13 (t,J = 7.9 Hz, 1H), 6.87 - 6.79 (m, 2H), 5.84 (dd, J = 5.2, 2.4 Hz, 1H), 2.76 (d, J = 4.9 Hz, 3H).

[0118] Step (g): Preparation of N-[2-bromo-4-(heptafluoroisopropyl)-6-(trifluoromethyl)phenyl]-2-fluoro-3-(N-methylbenzenesulfonamido)benzamide

[0119] In a 100 mL single-necked flask, add N-(2-bromo-4-(perfluoroprop-2-yl)-6-(trifluoromethyl)phenyl)-2-fluoro-3-(methylamino)benzamide (100.00 mg, 178.83 µmol), benzenesulfonyl chloride (41.06 mg, 232.48 µmol), 4-dimethylaminopyridine (2.18 mg, 17.88 µmol), triethylamine (37.29 μL, 268.25 µmol), and 15 mL of toluene, and heat to 110 °C. oThe reaction mixture was refluxed at C for 18 hours. After the reaction was complete, the reaction solution was extracted three times with 50 mL of EA, washed three times with 30 mL of saturated brine, dried for half an hour with a small amount of anhydrous sodium sulfate, filtered, and the filtrate was concentrated under reduced pressure to obtain the crude product. This crude product was then purified by column chromatography (eluent was petroleum ether (PE) and ethyl acetate (EA) in a volume ratio of 9:1) to obtain a pale yellow powder, which was the target compound Ib-1, with a yield of 73.90%. Melting point: 165-166 °C; 1H NMR spectrum: 1 H NMR (400 MHz, DMSO-d6) δ 10.77 (s, 1H), 8.43 (d, J = 2.1 Hz, 1H), 7.97 (d, J = 2.2 Hz, 1H), 7.70 (ddt, J = 24.7, 15.3, 7.5 Hz, 6H), 7.42 – 7.34 (m, 2H), 3.19 (s, 3H); MS(ESI+), m / z ([M+H] + calcd for C 24 H 15 BrF 11 N2O3S 698.9806, found 698.9815.

[0120] Example 4

[0121] This embodiment provides a sulfonamide-containing meta-diamide derivative, specifically N-[2-bromo-4-(heptafluoroisopropyl)-6-(trifluoromethyl)phenyl]-2-fluoro-3-[(4-fluoro-N-methylphenyl)sulfonamido]benzamide (Ib-2):

[0122] ;

[0123] The preparation of the above compound N-[2-bromo-4-(heptafluoroisopropyl)-6-(trifluoromethyl)phenyl]-2-fluoro-3-[(4-fluoro-N-methylphenyl)sulfonamido]benzamide (Ib-2) includes the following steps:

[0124] Steps (a) to (f) are the same as in Example 3;

[0125] Step (g): Preparation of N-[2-bromo-4-(heptafluoroisopropyl)-6-(trifluoromethyl)phenyl]-2-fluoro-3-[(4-fluoro-N-methylphenyl)sulfonamido]benzamide

[0126] In a 100 mL single-necked flask, add N-(2-bromo-4-(perfluoroprop-2-yl)-6-(trifluoromethyl)phenyl)-2-fluoro-3-(methylamino)benzamide (100.00 mg, 178.83 µmol), 4-fluorobenzenesulfonyl chloride (45.24 mg, 232.48 µmol), 4-dimethylaminopyridine (2.18 mg, 17.88 µmol), triethylamine (37.29 μL, 268.25 µmol), and 15 mL of toluene, and heat to 110 °C. o The reaction mixture was refluxed at C for 18 hours. After the reaction was complete, the reaction solution was extracted three times with 50 mL of EA, washed three times with 30 mL of saturated brine, dried for half an hour with a small amount of anhydrous sodium sulfate, filtered, and the filtrate was concentrated under reduced pressure to obtain the crude product. This crude product was then purified by column chromatography (eluent: petroleum ether (PE) and ethyl acetate (EA) in a volume ratio of 9:1) to obtain a pale yellow powder, which was the target compound Ib-2, with a yield of 71.38%. Melting point: 168-170 °C; 1H NMR spectrum: 1 H NMR (400MHz, DMSO-d6) δ 10.72 (s, 1H), 8.43 (d, J = 2.1 Hz, 1H), 7.96 (d, J = 2.2 Hz, 1H), 7.80 - 7.74 (m, 2H), 7.72 - 7.67 (m, 1H), 7.50 - 7.36 (m, 4H), 3.20 (s,3H); MS(ESI+), m / z ([M+H] + calcd for C 24 H 13 BrF 12 N2O3S 716.9711, found 716.9702.

[0127] Compounds Ia-2, Ia-4, Ia-5, and Ib-3 to Ib-7 were prepared using a method similar to that used in Examples 1 to 4. The structural formulas and test data of each compound are shown below.

[0128] Compound Ia-2 has the following structural formula: Melting point, 1H NMR, and mass spectrometry data are as follows:

[0129] Melting point 156-158 °C; 1H NMR (400 MHz, DMSO-d6) δ 10.70 (d, J = 2.2 Hz, 1H), 10.45 (d, J = 2.2 Hz, 1H), 8.42 (s, 1H), 7.95 (s, 1H), 7.84 (ddd, J = 9.0,5.1, 2.2 Hz, 2H), 7.53 – 7.39 (m, 4H), 7.32 (td, J = 7.9, 2.2 Hz, 1H); MS(ESI+), m / z ([M+H] + calcd for C 23 H 12 BrF 12 N2O3S 702.9555, found 702.9555.

[0130] Compound Ia-4 has the following structural formula: The melting point, 1H NMR, and mass spectrometry data are as follows:

[0131] Melting point 165-169 °C; 1 H NMR (400 MHz, DMSO-d6) δ 10.70 (s, 1H), 10.67 (s,1H), 8.42 (d, J = 2.1 Hz, 1H), 8.11 – 8.06 (m, 2H), 7.97 – 7.90 (m, 3H), 7.56– 7.43 (m, 2H), 7.33 (t, J = 7.9 Hz, 1H); MS(ESI+), m / z ([M+H] + ) calcd forC 24 H 12 BrF 11 N3O3S 709.9602, found 709.9611.

[0132] Compound Ia-5 has the following structural formula: The melting point, 1H NMR, and mass spectrometry data are as follows:

[0133] Melting point 148-149 °C; 1H NMR (400 MHz, DMSO-d6) δ 10.69 (s, 1H), 10.51 (s,1H), 8.41 (d, J = 2.1 Hz, 1H), 7.95 (d, J = 2.2 Hz, 1H), 7.84 – 7.78 (m, 2H),7.71 – 7.66 (m, 2H), 7.48 (dtd, J = 20.4, 7.7, 1.8 Hz, 2H), 7.32 (t, J = 7.9Hz, 1H); MS(ESI+), m / z ([M+H] + calcd for C 23 H 12 Br2F 11 N2O3S 762.8754, found762.8759.

[0134] Compound Ib-3 has the following structural formula: The melting point, 1H NMR, and mass spectrometry data are as follows:

[0135] Melting point 155-158 °C; 1 H NMR (400 MHz, DMSO-d6) δ 10.78 (s, 1H), 8.43 (d, J= 2.2 Hz, 1H), 7.99 – 7.95 (m, 1H), 7.75 – 7.68 (m, 2H), 7.68 – 7.62 (m, 1H),7.56 (ddt, J = 14.9, 8.3, 1.9 Hz, 2H), 7.47 – 7.37 (m, 2H), 3.23 (s, 3H); MS(ESI+), m / z ([M+H] + calcd for C 24 H 14 BrF 12 N2O3S 716.9711, found 716.9704.

[0136] Compound Ib-4 has the following structural formula: The melting point, 1H NMR, and mass spectrometry data are as follows:

[0137] Melting point 157-159 °C; 1H NMR (400 MHz, DMSO-d6) δ 10.78 (s, 1H), 8.43 (d, J= 2.1 Hz, 1H), 7.97 (d, J = 2.2 Hz, 1H), 7.84 – 7.77 (m, 1H), 7.71 (dtd, J =9.4, 7.7, 1.8 Hz, 2H), 7.51 (dd, J = 7.8, 5.4 Hz, 2H), 7.43 – 7.36 (m, 2H),3.30 (s, 3H); MS(ESI+), m / z ([M+H] + calcd for C 24 H 14 BrF 12 N2O3S 716.9711, found716.9702.

[0138] Compound Ib-5 has the following structural formula: The melting point, 1H NMR, and mass spectrometry data are as follows:

[0139] Melting point 153-156 °C; 1 H NMR (400 MHz, DMSO-d6) δ 10.77 (s, 1H), 8.44 (d, J= 2.0 Hz, 1H), 7.99 – 7.96 (m, 1H), 7.71 (s, 5H), 7.48 – 7.37 (m, 2H), 3.20(s, 3H); MS(ESI+), m / z ([M+H] + calcd for C 24 H 14 BrClF 11 N2O3S 732.9416, found732.9406.

[0140] Compound Ib-6 has the following structural formula: The melting point, 1H NMR, and mass spectrometry data are as follows:

[0141] Melting point 169-171 °C; 1H NMR (400 MHz, DMSO-d6) δ 9.94 (s, 1H), 7.62 (d, J =2.1 Hz, 1H), 7.17 – 7.14 (m, 1H), 7.07 – 7.01 (m, 2H), 6.88 (ddd, J = 7.5,6.2, 2.0 Hz, 1H), 6.84 – 6.78 (m, 2H), 6.66 – 6.54 (m, 2H), 2.39 (s, 3H); MS(ESI+), m / z ([M+H] + calcd for C 24 H 14 Br2F 11 N2O3S 776.8911, found 776.8917.

[0142] Compound Ib-7 has the following structural formula: The melting point, 1H NMR, and mass spectrometry data are as follows:

[0143] Melting point 159-161 °C; 1 H NMR (400 MHz, DMSO-d6) δ 10.76 (s, 1H), 8.44 (d, J= 2.1 Hz, 1H), 8.18 – 8.08 (m, 2H), 7.99 – 7.95 (m, 1H), 7.91 – 7.84 (m, 2H),7.72 (ddd, J = 7.7, 6.1, 2.0 Hz, 1H), 7.50 – 7.36 (m, 2H), 3.24 (s, 3H); MS(ESI+), m / z ([M+H] + calcd for C 25 H 14 BrF 11 N3O3S 723.9758, found 723.9747.

[0144] As can be seen from the above examples, the melting point of the compound obtained by the present invention is 149~171 °C, and the molecular weight is 683~776.

[0145] Insecticidal activity test of sulfonamide-containing metadiamide derivatives

[0146] The insecticidal activity of 12 compounds (Ia-1~Ia-5 and Ib-1~Ib-5) against third-instar diamondback moth and corn borer was determined using the leaf dipping method at concentrations of 200 mg / L and 100 mg / L. The LC-100 of some compounds against third-instar diamondback moth was also analyzed.50 value.

[0147] Specifically, reagents and materials:

[0148] Technical grade drugs: compounds Ia-1~Ia-5, Ib-1~Ib-5;

[0149] Reagents: DMSO (analytical grade), Tween 80, pure water;

[0150] Biological materials: diamondback moth, corn borer; baby bok choy, corn leaves.

[0151] Experimental methods

[0152] (1) Test methods for the insecticidal activity of the compound against third-instar diamondback moth and corn borer at concentrations of 200 mg / L and 100 mg / L

[0153] Prepare a 0.1% Tween 80 aqueous solution (add 0.5 mL of Tween 80 to 500 mL of deionized water and mix thoroughly).

[0154] Preparation of 100 mg / L stock solution: Accurately weigh 10 mg of the sample to be tested (i.e., the sulfonamide-containing m-diamide derivative of the present invention) using an electronic balance, dissolve it in 0.5 mL of DMSO, add the DMSO solution of the sample to be tested to 100 mL of prepared 0.1% Tween 80 aqueous solution and sonicate to mix well for later use.

[0155] Preparation of 50 mg / L stock solution: Accurately weigh 5 mg of the sample to be tested using an electronic balance, dissolve it in 0.5 mL of DMSO, add the DMSO solution of the sample to be tested into 50 mL of prepared 0.1% Tween 80 aqueous solution and sonicate to mix well for later use.

[0156] Immersion treatment: Select baby bok choy or corn leaves that grow uniformly and make leaf discs with a diameter of 2 cm using a hole punch; immerse the leaf discs in the prepared solution for 15 seconds, remove them and let them air dry naturally; place the treated leaf discs in a petri dish lined with moist filter paper.

[0157] Inoculation and rearing: Use a small paintbrush to gently pick up 12 healthy 3rd instar diamondback moth larvae or corn borer larvae of the same size and inoculate each culture dish;

[0158] Each treatment was repeated in triplicate, with a blank control (0.1% Tween 80 aqueous solution). The petri dishes were placed in a constant temperature incubator at 26 ℃, 40% relative humidity, and a light-dark cycle of 16 h:8 h, with leaf discs replenished as needed. The number of live and dead larvae was recorded after 24 h.

[0159] Criteria for determining death: If the insect does not react when lightly touched with a small paintbrush, or if the insect is shriveled or discolored, it is considered dead.

[0160] Record the number of dead insects in each treatment, and calculate the mortality rate and corrected mortality rate according to formulas (1) and (2).

[0161] Calculate according to formulas (1) and (2), and keep the calculation results to two decimal places.

[0162] (1);

[0163] Where P represents the mortality rate, expressed as a percentage (%);

[0164] K represents the number of dead insects in each group, in units of heads;

[0165] N represents the total number of insects treated in each group, in units of heads.

[0166] N represents the total number of insects treated in each group, in units of heads.

[0167] (2);

[0168] Where P1 represents the corrected mortality rate, expressed as a percentage (%);

[0169] P t The treatment mortality rate (i.e., the mortality rate treated with the sulfonamide-containing metadiamide derivatives of the present invention) is expressed as a percentage (%).

[0170] P0 represents the mortality rate in the blank control group, expressed as a percentage (%).

[0171] If the mortality rate of the blank control is <5%, no correction is needed; if the mortality rate of the blank control is between 5% and 20%, it should be corrected according to formula (2); if the mortality rate of the control is >20%, the experiment needs to be repeated.

[0172] (2) LC-12 of some compounds on zebrafish 50 Value testing methods

[0173] Preparation of the drug solution: Prepare a 0.1% Tween 80 aqueous solution (add 0.5 mL of Tween 80 to 500 mL of deionized water and mix thoroughly).

[0174] Accurately weigh an appropriate amount of the compound to be tested, dissolve it in 0.5 mL of DMSO, and add it to a 0.1% Tween 80 aqueous solution to prepare a 30 mg / L stock solution. Use a stepwise dilution method to dilute the stock solution sequentially (using a 0.1% Tween 80 aqueous solution) to obtain concentration gradient solutions of 30 mg / L, 15 mg / L, 10 mg / L, 5 mg / L and 1 mg / L.

[0175] For the exposure treatment, zebrafish were randomly divided into groups of 10 each in a container (such as a beaker or culture tank). Each treatment group was given the corresponding concentration of drug solution (30 mg / L, 15 mg / L, 10 mg / L, 5 mg / L, 1 mg / L). A blank control (0.1% Tween 80 aqueous solution) and a positive control (1 mg / L~30 mg / L bromuconazole) were also included. A control group was also included. Each treatment was repeated three times.

[0176] All treatment containers were placed in a constant temperature incubation environment with the following conditions: temperature: 26 ± 1 ℃; light-dark cycle: 14h:10h or 16h:8h; sufficient dissolved oxygen (avoiding hypoxia); static non-water-change method was used during the experiment (24h).

[0177] Mortality was recorded after 48 hours of exposure, and the mortality rate of zebrafish at each concentration was calculated.

[0178] The same experimental protocol was used to correct for mortality rates.

[0179] The target compound of this invention showed strong insecticidal activity against third-instar diamondback moth larvae and third-instar corn borer larvae at concentrations of 100 mg / L and 50 mg / L, respectively. The experimental data are shown in Tables 1 and 2.

[0180] Table 1 - Insecticidal activity of different target compounds against third-instar diamondback moth larvae

[0181]

[0182] Table 2 - Insecticidal activity of different target compounds against third-instar corn borer larvae

[0183]

[0184] In Tables 1-2, the corrected mortality rate (% ± SD) represents the corrected mortality rate ± standard deviation (SD) for each repeated experiment.

[0185] Compounds Ia-2, Ia-4, and Ia-5, which exhibit high activity against third-instar diamondback moth and corn borer larvae at a concentration of 50 mg / L, as well as brofenoxam, were selected and their lethality rates against zebrafish at different concentrations were investigated. The results are shown in Table 3. Furthermore, their 48-h acute toxicity (LC50) against zebrafish was determined. 50 The results are shown in Table 4.

[0186] Table 3 - Lethality of some compounds in zebrafish

[0187]

[0188] Table 4 - LC50 of some compounds in zebrafish 50 value

[0189]

[0190] As shown in Tables 1 and 2, at 100 mg / L, all 12 compounds exhibited insecticidal activity against third-instar diamondback moth and corn borer larvae. Compounds Ia-1, Ia-2, Ia-4, Ia-5, Ib-4, and Ib-6 showed insecticidal activity exceeding 90% against third-instar diamondback moth, while compounds Ia-2, Ia-4, and Ia-5 also showed insecticidal activity exceeding 90% against corn borer larvae. Compounds Ia-2 and Ia-5 showed a 24-hour lethality of 100% against both third-instar diamondback moth and corn borer larvae.

[0191] At 50 mg / L, all 12 compounds showed insecticidal activity against third-instar diamondback moth and corn borer larvae, but the overall insecticidal activity was slightly reduced. Among them, compounds Ia-2, Ia-4, and Ia-5 all had a 24-hour lethality greater than 90% against third-instar diamondback moth and corn borer larvae.

[0192] In addition, Tables 3 and 4 show the lethality and LC-12 concentrations of the compounds at various concentrations in zebrafish after 48 hours of toxicity testing. 50 The results showed that compounds Ia-2, Ia-4, and Ia-5 were all less toxic than the positive control, bromfenac. According to the toxicity classification standards of the "Guidelines for Environmental Safety Evaluation Tests of Chemical Pesticides" (GB / T 31270.12-2014), compound Ia-4 had the lowest LC50 concentration in zebrafish. 50 The concentration was 9.6 mg / L, which falls into the category of poisoning (1.0 < LC50). 50 ≤ 10 mg / L); LC5 of compounds Ia-2 and Ia-5 on zebrafish 50 The concentrations were 18.9 mg / L and 32.7 mg / L, respectively, which fall into the low toxicity category (LC50). 50 >10 mg / L), which is generally better than the toxicity level of bromfenac in zebrafish (1.0 < LC). 50 (≤10 mg / L), low environmental risk.

[0193] In summary, the sulfonamide-containing m-diamide derivatives of general formula I, such as Ia-2 and Ia-5, exhibit good insecticidal activity against diamondback moth and corn borer. They can significantly reduce acute toxicity to zebrafish while maintaining the activity of existing m-diamide insecticides, demonstrating low aquatic biological toxicity and low environmental risk.

[0194] In summary, this invention designed and synthesized a class of sulfonamide-containing metadiamide derivatives, and conducted systematic bioactivity screening and evaluation to provide highly active candidate compounds for the creation of new pesticides. The above activity experiments show that the target compounds of this invention have significant insecticidal activity and good broad-spectrum activity, demonstrating promising application prospects as novel insecticides. Furthermore, some compounds exhibit low aquatic toxicity and low environmental risk.

[0195] The above description is only a preferred embodiment of the present invention and is not intended to limit the present invention. Any modifications, equivalent substitutions, improvements, etc., made within the spirit and principles of the present invention should be included within the protection scope of the present invention.

Claims

1. A sulfonamide-containing meta-diamide derivative, characterized in that, It includes compounds as shown in general formula I, or their stereoisomers, polymorphs, isotopic derivatives, and pesticide-acceptable salts: ； General Formula I; Wherein, R1 is an optionally substituted C1-C6 alkyl, C3-C6 cycloalkyl, optionally substituted aryl, or optionally substituted saturated alkyl. And / or any of the unsaturated heterocyclic groups; The substituents on R1 are selected from H, alkoxy, halogen, cyano, hydroxy, nitro, amino, mercapto, and optional substituents. One or more of the following: alkyl, optionally substituted alkyloxy, optionally substituted alkylthio, or optionally substituted alkylamino; The R2 is any one of H, C1-C6 alkyl, C1-C6 alkoxy, C1-C6 haloalkyl, C1-C6 cyanoalkyl, C1-C6 hydroxyalkyl, C1-C6 nitroalkyl, C1-C6 aminoalkyl, C1-C6 haloalkoxy-C1-C6 alkyl, C3-C6 cycloalkyl, and C3-C6 substituted cycloalkyl.

2. The sulfonamide-containing meta-diamide derivative as described in claim 1, characterized in that, R1 is selected from any one of phenyl, o-fluorophenyl, m-fluorophenyl, p-fluorophenyl, p-chlorophenyl, p-bromophenyl, p-tolyl, p-cyanophenyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, pyridinyl, pyrimidinyl, pyrazinyl, naphthyl, indolyl, oxazolyl, isoxazolyl, thiazolyl, isothiazolyl, furanyl, thiophenyl, and pyrroleyl. The R2 is selected from H, C1-C4 alkyl, C1-C4 cycloalkyl, C1-C4 alkoxy, C1-C4 cyanoalkyl, and C1-C4 aminoalkyl.

3. The sulfonamide-containing meta-diamide derivative as described in any one of claims 1 to 2, characterized in that, Choose any one of the following formulas: Ia-1 to Ia-5, Ib-1 to Ib-7; 。 4. A method for preparing a sulfonamide-containing meta-diamide derivative as described in any one of claims 1 to 3, characterized in that, When R2 is H, the preparation method of the sulfonamide-containing meta-diamide derivative includes the following steps: (a) Compound II-1: 2-(trifluoromethyl)aniline was mixed with heptafluoroisopropyliodine, a single-electron reducing agent, a phase transfer catalyst and solvent A to undergo an electrophilic substitution reaction to obtain compound II-2: 4-(heptafluoroisopropyl)-2-(trifluoromethyl)aniline. (b) Compound II-3: 2-fluoro-3-nitrobenzoic acid was dispersed in an acyl chloride reagent and subjected to a nucleophilic addition-elimination reaction. Compound II-4 was obtained: 2-fluoro-3-nitrobenzyl chloride; (c) Compound II-4 and compound II-2 were dispersed in solvent B, and a catalyst and an acid-binding agent were added to obtain compound II-5: 2-fluoro-3-nitro-N-[4-(heptafluoroisopropyl)-2-(trifluoromethyl)phenyl]benzamide; (d) Compound II-5, along with a base and sodium bromide, was dispersed in solvent C, and an oxidizing agent was added to obtain compound II-6: N-[2-bromo-4-(heptafluoroisopropyl)-6-(trifluoromethyl)phenyl]-2-fluoro-3-nitrobenzamide; (e) Compound II-6 and the reducing agent were dispersed in solvent D, and acid was added to obtain compound II-7: 3-amino-N-[2- [Bromo-4-(heptafluoroisopropyl)-6-(trifluoromethyl)phenyl]-2-fluorobenzamide; (f) Compounds II-7 and II-8 are dispersed in solvent E, and a catalyst and an acid-binding agent are added to obtain the sulfonamide-containing meta-diamide derivative; the structural formula of compound II-8 is as follows: ; When R2 is not H, the preparation method of the sulfonamide-containing meta-diamide derivative includes the following steps: Compound II-7, 3-amino-N-[2-bromo-4-(heptafluoroisopropyl)-6-(trifluoromethyl)phenyl]-2-fluorobenzamide, was prepared according to steps (a) to (e) above. (g) Compounds II-7 and II-9 are dispersed in solvent F, and acid is added to obtain compound II-10; wherein, compound II-9 is R3CHO, and the structural formula of compound II-10 is [insert structural formula here]. In compound II-10, R2 is R3-CH2-; (h) Disperse the compound II-10 and the compound II-8 in solvent E, and add a catalyst and an acid-binding agent to obtain the sulfonamide-containing meta-diamide derivative.

5. The method for preparing sulfonamide-containing meta-diamide derivatives as described in claim 4, characterized in that, In step (a), the molar ratio of 2-(trifluoromethyl)aniline, heptafluoroisopropyl iodine, single-electron reducing agent and phase transfer catalyst is 1:(2.0~2.5):(2.5~3.0):(0.05~0.1); The single-electron reducing agent includes at least one of sodium dithionite, sodium ascorbate, sodium bisulfite, and sodium metabisulfite; The phase transfer catalyst includes at least one of tetrabutylammonium bromide, tetrabutylammonium chloride, and hexadecyltrimethylammonium bromide; Solvent A is any one of the following: a mixed solvent of ethyl acetate and water, a mixed solvent of methyl tert-butyl ether and water, or a mixed solvent of dichloromethane and water; The reaction temperature is 50~60 °C, and the reaction time is 4~6 h; In step (b), the acyl chloride reagent is one of thionyl chloride and oxalyl chloride, the reaction temperature is 80~90 °C, and the reaction time is 3~4 h.

6. The method for preparing sulfonamide-containing meta-diamide derivatives as described in claim 4, characterized in that, In step (c), the molar ratio of compound II-4, compound II-2, catalyst, and acid-binding agent is (1.1~1.2):1:(0.01~0.02):(1.2~1.5); The catalyst is either 4-dimethylaminopyridine or 4-pyrrolidinylpyridine; The acid-binding agent is any one of triethylamine, N,N-diisopropylethylamine, and pyridine; Solvent B is any one of pyridine, 1,3-dichloropropane, toluene, and chlorobenzene; The reaction temperature is 100~110 °C, and the reaction time is 5~7 h; In step (d), the molar ratio of compound II-5, base, sodium bromide and oxidizing agent is 1:1:(2.0~2.5):(2.5~3.0); The alkali is either sodium hydroxide or potassium hydroxide; The oxidizing agent is any one of sodium hypochlorite, sodium hypobromite, and hydrogen peroxide; The solvent C is any one of dichloromethane, 1,2-dichloroethane, and chloroform; The reaction temperature is 50~60 °C, and the reaction time is 5~6 h; In step (e), the molar ratio of compound II-6, reducing agent, and acid is 1:(2.0~2.5):(2.0~2.5); The reducing agent is any one of iron powder, zinc powder, tin powder, and stannous chloride; The acid is either hydrochloric acid or acetic acid; The solvent D is any one of methanol, ethanol, ethyl acetate, and dioxane; The reaction temperature is 60~80 °C, and the reaction time is 5~6 h; In step (f), the molar ratio of compound II-7, compound II-8, catalyst, and acid-binding agent is 1:(1.1~1.3):(0.05~0.10):(1.2~1.5); The catalyst is either 4-dimethylaminopyridine or 4-pyrrolidinylpyridine; The acid-binding agent is any one of triethylamine, pyridine, and N,N-diisopropylethylamine; The solvent E is any one of pyridine, dichloromethane, acetonitrile, tetrahydrofuran, and N,N-dimethylformamide; The reaction temperature is 40~60 °C, and the reaction time is 6~8 h.

7. The method for preparing sulfonamide-containing meta-diamide derivatives as described in claim 4, characterized in that, In step (g), the molar ratio of compound II-7, compound II-9, and acid is 1:(1.1~2.0):(1.2~2.5); The acid is either hydrochloric acid or sulfuric acid; The solvent F is either water or dioxane; The reaction temperature is 60~70 °C, and the reaction time is 5~6 h; In step (h), the molar ratio of compound II-10, compound II-8, catalyst, and acid-binding agent is 1:(1.1~1.3):(0.05~0.10):(1.2~1.5); The catalyst is either 4-dimethylaminopyridine or 4-pyrrolidinylpyridine; The acid-binding agent is any one of triethylamine, pyridine, and N,N-diisopropylethylamine; The solvent G is any one of pyridine, 1,3-dichloropropane, toluene, and chlorobenzene; The reaction temperature is 80~110 °C, and the reaction time is 12~20 h.

8. The use of a sulfonamide-containing metadiamide derivative as described in any one of claims 1 to 3 in the preparation of an insecticide.

9. An insecticide, characterized in that, Includes sulfonamide-containing metadiamide derivatives as described in any one of claims 1 to 3 and agriculturally acceptable carriers.

10. A method for controlling crop pests, characterized in that, Apply the sulfonamide-containing metadiamide derivative as described in any one of claims 1 to 3 or the insecticide as described in claim 9 to the crop.

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