A heptafluoroisopropyl-containing bisamide compound and its preparation method and application

Abstract

The present invention provides a compound of general formula (I-V), which is used for preparing a heptafluoroisopropyl-containing bisamide compound. The heptafluoroisopropyl bisamide compound has excellent insecticidal activity as verified by experiments, especially has excellent high insecticidal activity against resistant populations, has no cross-resistance with the existing insecticide chlorantraniliprole, has good insecticidal effect at low doses and good rapidity; in addition, the preparation method of the heptafluoroisopropyl bisamide compound is simple, efficient and easy to industrialize, and has broad application prospects in the prevention and control of insect pests in the fields of agriculture, forestry and horticulture.

Description

[0001] This divisional application is a divisional application of the Chinese invention patent application with application date of 2022-12-07, application number CN 2022115602361, and invention name “A bisamide compound containing heptafluoroisopropyl group, preparation method and application thereof”.

[0002] The present invention requests two domestic priorities, namely, an invention patent application with a priority date of December 22, 2021, priority number CN2021115835066, entitled “A bisamide compound containing a heptafluoroisopropyl group, and a preparation method and application thereof”, and an invention patent application with a priority date of September 23, 2022, priority number CN 2022111613460, and invention name “A bisamide compound containing a heptafluoroisopropyl group, and a preparation method and application thereof”. Technical Field

[0003] The invention belongs to the field of insecticides, relates to a diamide compound containing heptafluoroisopropyl, and also relates to a preparation method and application thereof. Technical Background

[0004] Neonicotinoid insecticides represented by imidacloprid are a class of super-efficient insecticides. The global market is currently stable at over US$2 billion. However, their frequent and extensive use has caused serious resistance. Chlorantraniliprole (structural formula: CK01), the "king pesticide" that has dominated the insecticide market for more than a decade, has also shown serious resistance problems in most parts of the world. The dosage must be increased to achieve the original effect, which is bound to cause certain problems to agricultural production, the environment, and the ecology.

[0005] The damage caused by pests is still very significant. Pests have developed resistance to existing pesticides and existing pesticides are not environmentally friendly. There is a need to develop new pesticides with better activity, lower dosage and better environmental friendliness. Domestic and foreign research institutions and enterprises continue to increase their investment in pesticide creation, and a number of new pesticides with high activity, low dosage and environmental friendliness have emerged.

[0006] Broflanilide (structural formula: CK02), a diamide insecticide jointly developed by Mitsui Chemicals and BASF, is now on the market. Its Chinese name is bromofenac, and it is mainly used for fruits, vegetables, beans, cotton, corn, grains, flowers and non-crop purposes to control lepidoptera, coleoptera, termites, ants, cockroaches, flies and other pests. It has very good effects. For details, see Chinese patent CN102119173B, amide derivatives, pest control agents containing the amide derivatives and methods of use. However, many domestic companies and research institutions have found that Broflanilide has poor fast-acting properties and poor insecticidal effects at low doses. On this basis, they have optimized and improved its structure and discovered a series of new insecticides with high activity, low dosage and environmental friendliness. For details, please refer to Chinese patent CN 109497062 B, a diamide compound and its preparation method and application, representative (structural formula: CK03); Chinese patent CN 110194726 B, a benzamide compound and its application, representative (structural formula: CK04). This provides more drug options in crop production such as agriculture and horticulture.

[0007]

[0008] Our research found that the insecticidal effects of the compounds of formula: CK02, formula: CK03 and formula: CK04 on certain resistant pests at low doses still need to be improved, and although the rapid effect of the compounds of formula: CK03 and formula: CK04 has been improved, the total yield of the compound preparation is low and the process cost is high, which is not conducive to industrial production and large-scale application. In this field, it is still necessary to actively develop new insecticides that have high insecticidal activity at low doses, no cross-resistance, and have industrial prospects to meet the needs of agriculture and forestry. Summary of the invention

[0009] In view of the deficiencies in the prior art, the present invention aims to provide a heptafluoroisopropyl-containing bisamide compound and its preparation method and application through molecular structure optimization and modification, a new insecticide compound with no cross-resistance to existing insecticides, which can have high insecticidal activity and good rapidity at low doses, is beneficial to ecological and environmental protection, and meets the needs of agriculture, forestry and horticulture.

[0010] To achieve this object, the present invention adopts the following technical solutions.

[0011] First, the present invention provides a heptafluoroisopropyl-containing bisamide compound, wherein the heptafluoroisopropyl-containing bisamide compound has a structure shown in the following general structural formula (I):

[0012]

[0013] Wherein, m is independently represented by an integer of 1-3; n is independently represented by an integer of 0-5;

[0014] R 1 The substituents can be located at any substitutable position on the benzene ring. 1 are independently selected from H, fluoro, chloro, bromo, iodo, trifluoromethyl, methoxy, trifluoromethoxy, methyl, ethyl, methylsulfonyl, cyano or nitro;

[0015] When m is 2 or 3, R 1 The substituents may be the same or different;

[0016] R 2 Independently selected from C1-C5 alkyl or benzyl which may have any substituent.

[0017] Preferably, n is independently 1 or 2.

[0018] The structure represented by the general formula (I) of the present invention can have very good insecticidal activity at low dosages, even reaching 90%-100% insecticidal activity, has no cross-resistance with chlorantraniliprole, reduces the dosage of the agent in practical applications, and produces less drug residue during application, which is more beneficial to ecology and environmental protection.

[0019] In the present invention, as a preferred technical solution, in the general formula (I), when m=1; the heptafluoroisopropyl-containing bisamide compound has a structure shown in the following general formula (II):

[0020]

[0021]

[0022] Among them, R 1 are independently selected from H, fluoro, chloro, bromo, iodo, trifluoromethyl, methoxy, trifluoromethoxy, methyl, ethyl, methylsulfonyl, cyano or nitro;

[0023] R 2 Independently selected from C1-C5 alkyl or benzyl which may be optionally substituted;

[0024] n is independently represented by 1 or 2.

[0025]

[0026] In the present invention, as another preferred technical solution, in the general formula (II), R 1 When the position of the substituent is determined, the heptafluoroisopropyl-containing bisamide compound has a structure shown in the following general formula (III):

[0027]

[0028] Among them, R 1 are independently selected from H, fluoro, chloro, bromo, iodo, trifluoromethyl, methoxy, trifluoromethoxy, methyl, ethyl, methylsulfonyl, cyano or nitro;

[0029] R 2 independently selected from methyl, ethyl, n-propyl, isopropyl, n-butyl or isobutyl;

[0030] n is independently represented by 1 or 2.

[0031] In the present invention, as a particularly preferred technical solution, in the structure shown in general formula III, wherein R 1 independently selected from H, fluoro, trifluoromethyl, trifluoromethoxy, cyano or nitro;

[0032] R 2 independently selected from methyl, ethyl or n-propyl;

[0033] n is independently represented by 1 or 2.

[0034] Among them, when m=1, the representative compounds and CK02 physicochemical indicators are shown in Table 1 below:

[0035] Table 1

[0036]

[0037]

[0038] The specific chemical structural formulas and chemical names are representative as follows:

[0039]

[0040] 2-Fluoro-3-[(phenylcarbonyl)(2-methoxyethyl)amino]-N-[2-bromo-4-(1,1,1,2,3,3,3-heptafluoropropane-2-yl)-6-(trifluoromethyl)phenyl]benzamide

[0041]

[0042]

[0043] 2-Fluoro-3-[(phenylcarbonyl)(2-ethoxyethyl)amino]-N-[2-bromo-4-(1,1,1,2,3,3,3-heptafluoropropane-2-yl)-6-(trifluoromethyl)phenyl]benzamide

[0044]

[0045] 2-Fluoro-3-{[(4-fluorophenyl)carbonyl](2-methoxyethyl)amino}-N-[2-bromo-4-(1,1,1,2,3,3,3-heptafluoropropane-2-yl)-6-(trifluoromethyl)phenyl]benzamide

[0046]

[0047] 2-Fluoro-3-{[(4-fluorophenyl)carbonyl](2-ethoxyethyl)amino}-N-[2-bromo-4-(1,1,1,2,3,3,3-heptafluoropropane-2-yl)-6-(trifluoromethyl)phenyl]benzamide

[0048]

[0049] 2-Fluoro-3-{[(4-trifluoromethylphenyl)carbonyl](2-methoxyethyl)amino}-N-[2-bromo-4-(1,1,1,2,3,3,3-heptafluoropropane-2-yl)-6-(trifluoromethyl)phenyl]benzamide

[0050]

[0051] 2-Fluoro-3-{[(4-trifluoromethylphenyl)carbonyl](2-ethoxyethyl)amino}-N-[2-bromo-4-(1,1,1,2,3,3,3-heptafluoropropane-2-yl)-6-(trifluoromethyl)phenyl]benzamide

[0052]

[0053] 2-Fluoro-3-{[(4-cyanophenyl)carbonyl](2-methoxyethyl)amino}-N-[2-bromo-4-(1,1,1,2,3,3,3-heptafluoropropane-2-yl)-6-(trifluoromethyl)phenyl]benzamide

[0054]

[0055] 2-Fluoro-3-{[(4-cyanophenyl)carbonyl](2-ethoxyethyl)amino}-N-[2-bromo-4-(1,1,1,2,3,3,3-heptafluoropropane-2-yl)-6-(trifluoromethyl)phenyl]benzamide

[0056]

[0057] 2-Fluoro-3-{[(4-trifluoromethoxyphenyl)carbonyl](2-methoxyethyl)amino}-N-[2-bromo-4-(1,1,1,2,3,3,3-heptafluoropropane-2-yl)-6-(trifluoromethyl)phenyl]benzamide

[0058]

[0059] 2-Fluoro-3-{[(4-trifluoromethoxyphenyl)carbonyl](2-ethoxyethyl)amino}-N-[2-bromo-4-(1,1,1,2,3,3,3-heptafluoropropane-2-yl)-6-(trifluoromethyl)phenyl]benzamide

[0060]

[0061] 2-Fluoro-3-[(phenylcarbonyl)(3-methoxypropyl)amino]-N-[2-bromo-4-(1,1,1,2,3,3,3-heptafluoropropane-2-yl)-6-(trifluoromethyl)phenyl]benzamide

[0062]

[0063] 2-Fluoro-3-[(phenylcarbonyl)(3-ethoxypropyl)amino]-N-[2-bromo-4-(1,1,1,2,3,3,3-heptafluoropropane-2-yl)-6-(trifluoromethyl)phenyl]benzamide

[0064]

[0065] 2-Fluoro-3-[(4-fluorophenylcarbonyl)(3-methoxypropyl)amino]-N-[2-bromo-4-(1,1,1,2,3,3,3-heptafluoropropane-2-yl)-6-(trifluoromethyl)phenyl]benzamide

[0066]

[0067] 2-Fluoro-3-[(4-fluorophenylcarbonyl)(3-ethoxypropyl)amino]-N-[2-bromo-4-(1,1,1,2,3,3,3-heptafluoropropane-2-yl)-6-(trifluoromethyl)phenyl]benzamide

[0068]

[0069] 2-Fluoro-3-{[(4-trifluoromethylphenyl)carbonyl](3-methoxypropyl)amino}-N-[2-bromo-4-(1,1,1,2,3,3,3-heptafluoropropane-2-yl)-6-(trifluoromethyl)phenyl]benzamide

[0070]

[0071] 2-Fluoro-3-{[(4-trifluoromethylphenyl)carbonyl](3-ethoxypropyl)amino}-N-[2-bromo-4-(1,1,1,2,3,3,3-heptafluoropropane-2-yl)-6-(trifluoromethyl)phenyl]benzamide

[0072] The compound of the general formula (I) of the present invention can be prepared by the following method. Unless otherwise specified, the definitions of the groups in the reaction formula are the same as above. In addition, the raw materials and reagents used in the present invention are usually purchased directly from the market, and the content is industrial product specifications, unless otherwise specified. In order to realize the preparation method of the compound of the general formula (I) of the present invention, a synthetic route is designed, and the preparation method of the compound of the general formula (I) of the present invention is realized by the preparation method process of the following steps 1 and 2.

[0073] Step 1: Synthesize the intermediate compound of the following general formula (I-V):

[0074]

[0075] This is achieved through the following two preparation methods:

[0076] Preparation method Ⅰ-A: The raw materials of the benzoic acid general formula (Ⅰ-Ⅰ) are subjected to steps such as chlorination reaction, amidation reaction, N-alkylation reaction, and hydrolysis reaction to synthesize the intermediate compound of the general formula (Ⅰ-V). The reaction formula of the preparation method is as follows:

[0077]

[0078] Preparation Method I-A

[0079] Preparation method I-B can also be used: 3-amino-2-fluorobenzoic acid methyl ester raw material is first subjected to N-alkylation reaction, and then subjected to amidation reaction, hydrolysis reaction and other steps with benzoyl chloride raw material of general formula (I-II) to synthesize the intermediate compound of general formula (I-V). The preparation method reaction formula is as follows:

[0080]

[0081] Preparation Method I-B

[0082] The benzoic acid general formula (Ⅰ-Ⅰ) series raw materials and 3-amino-2-fluorobenzoic acid methyl ester raw materials involved in the preparation methods Ⅰ-A and Ⅰ-B are all known compounds, which are pharmaceutical and pesticide intermediates and can be directly purchased on the market. Chinese patent CN111320548A also discloses another method for the synthesis and preparation of 3-amino-2-fluorobenzoic acid methyl ester. Other esters of 3-amino-2-fluorobenzoic acid methyl ester such as 3-amino-2-fluorobenzoic acid ethyl ester, 3-amino-2-fluorobenzoic acid n-butyl ester, 3-amino-2-fluorobenzoic acid isobutyl ester, etc. are also generally applicable to the preparation method of the present invention, and the raw material of 3-amino-2-fluorobenzoic acid methyl ester is preferably used.

[0083] The acylating agents commonly used in the acylating reaction involved in the preparation methods Ⅰ-A and Ⅰ-B are: thionyl chloride, sulfuryl chloride, oxalyl chloride, methanesulfonyl chloride, benzoyl chloride, phosphorus trichloride, phosphorus pentachloride, phosphorus oxychloride or triphosgene, etc., preferably thionyl chloride is used, and the molar amount is 1.0-10.0 times that of the raw material of the benzoic acid general formula (Ⅰ-Ⅰ), and the preferred economic amount is 1.0-3.0 times. The solvent used in the acylating reaction is dichloromethane, chloroform, dichloroethane, toluene or xylene, etc., and the preferred solvent is dichloroethane or toluene, etc.; the acylating reaction temperature is generally 20-150°C, and the preferred reaction temperature is 40-100°C; the acylating reaction time is generally 1-5 hours, preferably 2-3 hours.

[0084] The acylating agent used in the amidation reaction involved in the preparation methods Ⅰ-A and Ⅰ-B is triethylamine, pyridine, N,N-diisopropylethylamine, N,N-dimethylaniline, tetramethylethylenediamine, sodium bicarbonate, sodium carbonate, potassium carbonate, sodium hydroxide, potassium hydroxide, lithium hydroxide, sodium methoxide, potassium methoxide, sodium tert-butoxide or potassium tert-butoxide, etc., preferably triethylamine or pyridine, the molar amount is 1.0-5.0 times that of the raw material of the series of benzoyl chloride general formula (Ⅰ-Ⅱ), and the preferred economic amount is 1.0-2.0 times; the solvent used in the amidation reaction is dichloromethane, chloroform, dichloroethane, tetrahydrofuran, dihydrogen peroxide, etc. Hexacyclopentane, dimethyl sulfoxide, acetonitrile, toluene, xylene, N,N-dimethylformamide, N,N-dimethylacetamide, N-methylpyrrolidone or 1,3-dimethyl-2-imidazolidinone, etc., preferably the solvent is dichloroethane, toluene, acetonitrile, N,N-dimethylformamide or 1,3-dimethyl-2-imidazolidinone, etc., the amount is 1-20 times the weight of the raw material of the general formula (Ⅰ-Ⅱ) series of benzoyl chloride, and the preferred economic amount is 2-5 times; the amidation reaction temperature is generally -5-150°C, and the preferred reaction temperature is 0-50°C; the reaction time is generally 1-4 hours, preferably 2-3 hours.

[0085] The general formula of the alkylating agent used in the N-alkylation reaction involved in the preparation methods Ⅰ-A and Ⅰ-B is:

[0086]

[0087] Wherein, X is a halogen, preferably bromine or iodine;

[0088] n is independently an integer of 0-5; preferably 1 or 2.

[0089] R 2 Independently represents C1-C5 alkyl or benzyl which may have any substituent; preferably methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, benzyl, p-chlorobenzyl, p-bromobenzyl, p-fluorobenzyl and the like.

[0090] The N-alkylating agent used in the present invention is generally a known compound, which is a pharmaceutical or pesticide intermediate, such as bromomethyl methyl ether, bromomethyl ethyl ether, 1-bromo-2-methoxyethane, 1-bromo-2-ethoxyethane, 1-bromo-3-methoxypropane, 1-bromo-3-ethoxypropane, 1-bromo-2-n-propoxyethane, etc., which can be purchased directly from the market or synthesized. The synthesis of the N-alkylating agent is detailed in references, such as the synthesis of 1-bromo-1-ethoxypropane by Wang Yan et al., Chinese Journal of Pharmaceutical Industry, 2004, 35(4), 203-204; the improved synthesis method of 1-bromo-3-alkoxypropane by Chen Fener et al., Chinese Journal of Pharmaceutical Industry, 1995, 26(2), 88-89; and the relevant embodiments of U.S. Patent No. 5264150. The molar amount of the N-alkylating agent is 1.0-5.0 times of the raw material of the general formula (I-III) or methyl 3-amino-2-fluorobenzoate, preferably 1.0-2.0 times; the N-alkylating agent is generally added to the reaction system by dropwise addition or once or in batches, preferably dropwise addition; the solvent used in the N-alkylation reaction is N,N-dimethylformamide, N,N-dimethylacetamide, N-methylpyrrolidone, 1,3-dimethyl-2-imidazolidinone, dimethyl sulfoxide, acetonitrile, toluene, xylene, tetrahydrofuran, dioxane or acetone, preferably N,N-dimethylformamide, N,N-dimethylacetamide or acetonitrile, and the amount is the raw material of the general formula (I-III) or methyl 3-amino-2-fluorobenzoate. The base used in the N-alkylation reaction is pyridine, N,N-diisopropylethylamine, N,N-dimethylaniline, sodium bicarbonate, sodium carbonate, potassium carbonate, sodium hydroxide, potassium hydroxide, lithium hydroxide, sodium methoxide, potassium methoxide, sodium tert-butoxide, potassium tert-butoxide, sodium hydride, sodium amide or lithium diisopropylamide, etc., preferably sodium carbonate, potassium carbonate or sodium hydride is used, and the molar amount of the base is 1.0-5.0 times of the raw material of the general formula (I-III) or 3-amino-2-fluorobenzoic acid methyl ester, and the preferred amount is 2.0-5.0 times; the N-alkylation reaction temperature is 20-200°C, and the preferred reaction temperature is 20-100°C; the N-alkylation reaction time is generally 2-12 hours, preferably 2-10 hours.

[0091] In this step 1, there are Preparation Method Ⅰ-A and Preparation Method Ⅰ-B. The total yield of Preparation Method Ⅰ-A is significantly higher than that of Preparation Method Ⅰ-B. Preparation Method Ⅰ-A is preferred.

[0092] Step 2: The synthesis of the compound of general formula (I) can also be achieved by the following two preparation methods.

[0093] One preparation method is that the intermediate compound of general formula (I-V) undergoes acyl chlorination reaction and then undergoes amidation reaction and bromination reaction with 4-(1,1,1,2,3,3,3-heptafluoropropane-2-yl)-2-(trifluoromethyl)aniline raw material to synthesize the compound of general formula (I). The preparation method is as follows:

[0094]

[0095] Preparation method II-A

[0096] Another preparation method can also be used:

[0097] The intermediate compound of general formula (I-V) is directly subjected to acyl chlorination reaction and amidated with 2-bromo-4-(1,1,1,2,3,3,3-heptafluoropropane-2-yl)-6-(trifluoromethyl)aniline raw material to directly synthesize the compound of general formula (I). The preparation method is as follows:

[0098]

[0099] Preparation method II-B

[0100] The acylating agent commonly used in the acylating reaction involved in the preparation method of this step is: thionyl chloride, sulfuryl chloride, oxalyl chloride, methanesulfonyl chloride, benzoyl chloride, phosphorus trichloride, phosphorus pentachloride, phosphorus oxychloride or triphosgene, etc., preferably thionyl chloride is used, and the molar amount is 1.0-10.0 times the molar amount of the raw material of the general formula (I-V), preferably 1.0-3.0 times; the solvent used for the acylating reaction is dichloromethane, chloroform, dichloroethane, acetonitrile, toluene or xylene, etc., preferably dichloroethane, toluene, etc.; the acylating reaction temperature is generally 20-150°C, preferably 40-100°C; the acylating reaction time is generally 1-5 hours, preferably 2-3 hours.

[0101] The preparation method of the raw material 4-(1,1,1,2,3,3,3-heptafluoropropane-2-yl)-2-(trifluoromethyl)aniline involved in the preparation method II-A of this step and the raw material 2-bromo-4-(1,1,1,2,3,3,3-heptafluoropropane-2-yl)-6-(trifluoromethyl)aniline involved in the preparation method II-B of this part have detailed preparation processes in Examples 1, 1-1, and 1-2 of Chinese Patent CN102119143B, and there are also a large number of reports in foreign journals, and the present application will not be described in detail. Their molar usage is usually 1.0-2.0 times of the raw material of general formula (I-VII), preferably 1.0-1.5 times.

[0102] The amidation reaction solvent involved in the preparation method Ⅱ-A and the preparation method Ⅱ-B in this step is N,N-dimethylformamide, N,N-dimethylacetamide, N-methylpyrrolidone, 1,3-dimethyl-2-imidazolidinone, dimethyl sulfoxide, acetonitrile, dichloroethane, toluene, xylene, tetrahydrofuran, dioxane or acetone, etc., preferably N,N-dimethylformamide, N-methylpyrrolidone, 1,3-dimethyl-2-imidazolidinone, acetonitrile or toluene, etc. The amount used is 1.0-20.0 times the weight of the raw material of the general formula (Ⅰ-Ⅶ), preferably 2-10 times; the base used in the amidation reaction involved in the preparation method Ⅱ-B in this step is tetramethylethylenediamine, sodium carbonate, potassium carbonate, sodium methoxide, potassium methoxide, sodium tert-butoxide, potassium tert-butoxide, sodium hydride, diisopropylamine lithium, etc., preferably tetramethylethylenediamine, sodium methoxide, potassium methoxide, sodium tert-butoxide, potassium tert-butoxide or sodium hydride, and the molar amount of the base is 1.0-5.0 times the molar amount of the raw material of the general formula (Ⅰ-Ⅶ), preferably 1.0-1.5 times;

[0103] The amidation reaction temperature involved in Preparation Method Ⅱ-A and Preparation Method Ⅱ-B in this step is -20-200°C, preferably 20-150°C; the reaction time is 2-20 hours, preferably 5-10 hours.

[0104] The bromination reaction involved in the preparation method Ⅱ-A in this step, the bromination reagent is N-bromosuccinimide, dibromohydantoin, phosphorus tribromide, phosphorus pentabromide, phosphorus oxybromide or liquid bromine, etc., preferably N-bromosuccinimide or dibromohydantoin, etc. The molar amount of the bromination reagent is 1.0-5.0 times the molar amount of the raw material of the general formula (Ⅰ-Ⅷ), preferably 1.0-1.5 times; the base of the bromination reaction is sodium bicarbonate, sodium carbonate, potassium carbonate, sodium hydroxide, potassium hydroxide, lithium hydroxide, sodium methoxide, potassium methoxide, sodium tert-butoxide, potassium tert-butoxide, sodium hydride, sodium amide, lithium diisopropylamide, etc., preferably sodium carbonate, potassium carbonate or sodium hydride, the molar amount of the base is 1.0-5.0 times the molar amount of the raw material of the general formula (Ⅰ-Ⅷ), preferably 1.0-1.5 times; the solvent of the bromination reaction is N,N-dimethylformamide, N,N- Dimethylacetamide, N-methylpyrrolidone, 1,3-dimethyl-2-imidazolidinone, dimethyl sulfoxide, acetonitrile, dichloroethane, toluene, xylene, tetrahydrofuran, dioxane or acetone, etc., preferably N,N-dimethylformamide, N-methylpyrrolidone, 1,3-dimethyl-2-imidazolidinone, acetonitrile or toluene, etc., the amount used is 1.0-20.0 times the weight of the raw material of general formula (Ⅰ-Ⅷ), preferably 2-10 times; the reaction temperature of the bromination reaction is 0-100°C, preferably 20-100°C; the reaction time is 2-20 hours, preferably 5-10 hours.

[0105] In this step 2, there are preparation methods Ⅱ-A and Ⅱ-B. The total yield of preparation method Ⅱ-A is significantly higher than that of preparation method Ⅱ-B. Preparation method Ⅱ-A is preferred.

[0106] In the present invention, operations such as distillation, vacuum distillation, filtration, drying, extraction, and layering involved in the preparation method are conventional operations, which are basic operations for general chemists and will not be described in detail here. For details, see the synthesis examples.

[0107] In the present invention, on the one hand, a heptafluoroisopropyl-containing bisamide compound of general formula (I) obtained by molecular structure optimization has excellent insecticidal activity, especially has excellent high insecticidal activity against resistant populations, has no cross-resistance with the existing insecticide chlorantraniliprole, has good insecticidal effect and good rapidity at low doses; on the other hand, the preparation method of the compound of general formula (I) of the present invention is simple, efficient, and easy to industrialize, and has broad application prospects in the control of insect pests in the fields of agriculture, forestry and horticulture.

[0108] In the present invention, the pests include Lepidoptera, Coleoptera, Hemiptera, Thysanoptera, Diptera, Orthoptera, Homoptera, Isoptera, Hymenoptera, spider mite pests and nematodes, mosquitoes, flies, ants, etc.

[0109] The compounds of the present invention have a wide range of applications, and the plants or ranges used mainly include the following categories: vegetables, such as cucumber, loofah, watermelon, melon, pumpkin, hanging melon, spinach, celery, cabbage, cabbage, gourd, pepper, eggplant, tomato, onion, ginger, garlic, leek, lettuce, kidney bean, rainbow bean, broad bean, radish, carrot, potato, yam; cereals, such as wheat, barley, corn, rice, sorghum; fruit trees, such as apple, pear, banana, citrus, grape, litchi, mango; flowers, peony, rose, flamingo; oil crops, such as peanut, soybean, rape, sunflower, sesame; sugar crops, such as beet, sugarcane; other crops, such as strawberry, potato, sweet potato, tobacco and tea. It can also be used in gardening, forestry, family hygiene, public health areas, etc. The above-listed plants or ranges have no limiting effect on the scope of use of the heptafluoroisopropyl-containing bisamide compounds of the present invention.

[0110] On the one hand, the application of the compound of the present invention can be formulated into a preparation for application, including a pesticide acceptable carrier, including a solid carrier or a liquid carrier. A heptafluoroisopropyl-containing bisamide compound of the general formula (I) is dissolved or dispersed in a carrier or formulated into a preparation as an active ingredient. The preparation can be prepared into a powder, a wettable powder, a soluble powder, a granule, a water-dispersible granule, a suspension, a microemulsion, an emulsion, an aqueous emulsion or an emulsifiable concentrate.

[0111] On the other hand, the application of the present invention also provides an insecticide composition. The heptafluoroisopropyl-containing bisamide compound of general formula (I) provided by the present invention has no cross-resistance with the existing insecticide chlorantraniliprole, and can be mixed with existing insecticides, which can improve the use effect of existing insecticides affected by resistance problems and expand the insecticide spectrum. Other mixed active ingredients can be one or more of the commonly used varieties such as chlorantraniliprole, abamectin, imidacloprid, pymetrozine, fipronil, dinotefuran, molluscamide, cartap, thiamethoxam, etc., preferably amide insecticide varieties are used. The insecticide composition includes an active component and an acceptable carrier in pesticides. The active component is at least one active component in the heptafluoroisopropyl-containing bisamide compound of general formula (I) described in the present invention, and the mixing percentage ratio with other active components ranges from 0.1% to 99.9%. DETAILED DESCRIPTION

[0112] The technical solution of the present invention is further described below through specific implementation methods. Those skilled in the art should understand that the embodiments are only used to help understand the present invention and should not be regarded as specific limitations of the present invention.

[0113] The raw materials described in the synthesis examples of the present invention are generally purchased from the market unless otherwise specified, and the content specification is usually ≥95%, and the content is not accurately calibrated. The percentage concentration described in the synthesis examples generally refers to the weight percentage concentration unless otherwise specified. The HPLC content data is the area-normalized content and is not accurately calibrated. The yield refers to the molar yield, and the yield data is also not accurately calibrated.

[0114] Synthesis Example 1 (Using Ⅰ-A and Ⅱ-A Preparation Methods)

[0115] Synthesis of 2-fluoro-3-[(phenylcarbonyl)(2-methoxyethyl)amino]-N-[2-bromo-4-(1,1,1,2,3,3,3-heptafluoropropane-2-yl)-6-(trifluoromethyl)phenyl]benzamide (structural formula SYN001).

[0116]

[0117] Step 1:

[0118] In a 250ml four-necked glass reaction bottle, add 100g of dichloroethane, 25g (0.20mol) of benzoic acid, and 72g (0.60mol) of thionyl chloride. Heat and reflux for reaction for 3-5 hours. Cool to room temperature. Transfer the reaction solution to a 500ml rotary evaporator and desolventize to 80°C to obtain an oily liquid of benzoyl chloride. Cool to about 25°C and add 25g of new dichloroethane to dissolve for later use.

[0119] In another 250ml four-necked glass reaction bottle, 100g of dichloroethane, 35g (0.20mol) of methyl 3-amino-2-fluorobenzoate, and 24g (0.30mol) of pyridine were added, and the mixture was cooled to 5-25°C in an ice bath, and the above benzoyl chloride reserve solution was added dropwise within 1 hour, and the mixture was reacted at 5-25°C for 1-2 hours. After the reaction was completed, 50ml of water was added, and the mixture was stirred for 0.5 hours. The solvent layer was obtained by stratification, and the mixture was transferred to a 500ml rotary evaporator, and the solvent was removed under reduced pressure to 80°C to obtain 53g of methyl 2-fluoro-3-[(phenylcarbonyl)amino]benzoate as a white solid, with a HPLC normalized content of 94% (yield of 91.2%) for standby use, and the mixture was directly used in the next step of the reaction without further treatment. The reaction formula is as follows:

[0120]

[0121] In another 250ml four-necked glass reaction bottle, 200g of N,N-dimethylformamide, 15g (0.10mol) of potassium carbonate, and 25g (0.086mol) of methyl 2-fluoro-3-[(phenylcarbonyl)amino]benzoate synthesized above were added, the temperature was raised to 45-55°C, 15.8g (0.11mol) of 1-bromo-2-methoxyethane was added dropwise within 1 hour, and the reaction was kept warm for about 5 hours, the temperature was lowered to room temperature, the reaction solution was poured into 500ml of ice water for precipitation, extracted with 150g of dichloromethane, separated, and the dichloromethane layer was transferred to a rotary evaporator and desolvated under reduced pressure to 80°C to obtain Oily liquid, add 50g methanol, 60g (0.15mol) of 10% liquid caustic soda, raise the temperature to 25-35℃, keep warm for about 2 hours, add 50g water, adjust the pH to 1-2 with 30% hydrochloric acid, add 150g dichloromethane for extraction, separate the layers, obtain the dichloromethane layer, transfer to a rotary evaporator and desolventize to 80℃ to obtain 25g of light brown oily liquid, solidify and crystallize after cooling, HPLC normalized content 90% (the yield of these two steps is 82.5%), which is 2-fluoro-3-[(2-methoxyethyl)(phenylcarbonyl)amino]benzoic acid (0.071mol) for standby use, without treatment, and directly used in the next step reaction. The reaction formula is as follows:

[0122]

[0123] Step 2: Synthesis of SYN001 compound

[0124] In a 250ml four-necked glass reaction bottle, add 200g of dichloroethane, 25g (0.071mol) of 2-fluoro-3-[(2-methoxyethyl)(phenylcarbonyl)amino]benzoic acid synthesized above, and 24g (0.20mol) of thionyl chloride, and react under reflux for 3-5 hours. Then cool to room temperature, transfer the reaction solution to a 500ml rotary evaporator, desolventize to 80°C, and obtain an acyl chloride oily liquid. Cool to about 25°C, add 150g of acetonitrile to dissolve, transfer to a reaction bottle, add 27.8g (0.08mol) of 4-(1,1,1,2,3,3,3-heptafluoropropane-2-yl)-2-(trifluoromethyl)aniline raw material, and heat to reflux for 5-10 hours. The mixture was cooled to room temperature, poured into 300 ml of ice water for precipitation, extracted with 200 g of dichloroethane, washed with 50 ml of water and separated into layers to obtain a dichloroethane layer, dried over anhydrous magnesium sulfate and filtered, and desolventized to 80 ° C to obtain an oily 2-fluoro-3-[(phenylcarbonyl)(2-methoxyethyl)amino]-N-[4-(1,1,1,2,3,3,3-heptafluoropropane-2-yl)-6-(trifluoromethyl)phenyl]benzamide intermediate. 250 g of N,N-dimethylformamide was added to dissolve the mixture, and the reaction solution was transferred to a 500 ml reaction bottle, cooled to 0-25 ° C, 18 g (0.1 mol) of N-bromosuccinimide was added, and the reaction was kept warm for 5-10 hours. Pour into 500ml ice water to precipitate, extract with 200g dichloromethane, wash with 50ml water to separate the layers, obtain the dichloromethane layer, desolventize to 80°C, and obtain 54g crude product of oily 2-fluoro-3-[(phenylcarbonyl)(2-methoxyethyl)amino]-N-[2-bromo-4-(1,1,1,2,3,3,3-heptafluoropropane-2-yl)-6-(trifluoromethyl)phenyl]benzamide (i.e., structural formula SYN001), HPLC normalized content 85%, this step has a total of three steps of reaction yield based on 2-fluoro-3-[(2-methoxyethyl)(phenylcarbonyl)amino]benzoic acid 91.4%. The reaction formula is as follows:

[0125]

[0126]

[0127] 54 g of the crude compound was recrystallized with a mixed solvent of 150 g of n-hexane and 50 g of ethyl acetate at 0-5°C to obtain 40 g of white crystalline dry product, HPLC normalized content 96%, melting point: 179.5-180.5, crystallization yield 83.6%, and the total yield after step 2 crystallization was 76.5%.

[0128] The NMR and mass spectrometry data are as follows:

[0129] The H NMR spectrum was measured using a Bruker AV-400 spectrometer (400 MHz), TMS was used as the internal standard, and DMSO-d6 was used as the solvent (the same below); the high-resolution mass spectrum was measured using a UHR-TOF maXis (ESI) mass spectrometer (the same below).

[0130] 1 H-NMR(400MHz,DMSO-d6)δ(ppm):10.57(s,1H,CONH),8.39(s,1H),7.92(s,1H),7.61 -7.51(m,3H),7.34-7.24(m,5H),4.32-3.70(m,2H),3.68-3.45(m,2H),3.19(s,3H). HRMS(ESI)calcd.for C 27 H 18 F 11 N2NaO3[(M+Na) + ]:729.0223[(M+Na) + ],731.0202[(M+2+Na) + ]; Found:729.0213[(M+Na) + ],731.0196[(M+2+Na) + ].

[0131] Synthesis Example 2 (Using Ⅰ-A and Ⅱ-B Preparation Methods)

[0132] Synthesis of 2-fluoro-3-[(phenylcarbonyl)(2-methoxyethyl)amino]-N-[2-bromo-4-(1,1,1,2,3,3,3-heptafluoropropane-2-yl)-6-(trifluoromethyl)phenyl]benzamide (structural formula SYN001).

[0133] Step 1: 2-Fluoro-3-[(2-methoxyethyl)(phenylcarbonyl)amino]benzoic acid (0.071 mol). The synthesis feed and operation are the same as those in Step 1 of Synthesis Example 1.

[0134] Step 2: Synthesis of SYN001 compound

[0135] In a 250ml four-necked glass reaction bottle, 200g of dichloroethane, 25g (0.071mol) of 2-fluoro-3-[(2-methoxyethyl)(phenylcarbonyl)amino]benzoic acid synthesized in step 1 of Example 1, and 24g (0.20mol) of thionyl chloride were added, and the mixture was heated to reflux for 3-5 hours, cooled to room temperature, and the reaction solution was transferred to a 500ml rotary evaporator, desolvated to 80°C under reduced pressure to obtain an acyl chloride oily liquid, cooled to about 25°C, 150g of N,N-dimethylformamide was added to dissolve, and the mixture was transferred to a reaction bottle, and 35g (0.08mol) of 2-bromo-4-(1,1,1,2,3,3,3-heptafluoropropane-2-yl)-6-(trifluoromethyl)aniline raw material was added. Potassium methoxide 5.8g (0.08mol), heated to 55℃-65℃ for reaction for 5-10 hours, cooled to room temperature, poured into 500ml ice water for precipitation, extracted with 200g dichloromethane, washed with 50ml water to obtain a dichloromethane layer, desolventized to 80℃, and obtained an oily 2-fluoro-3-[(phenylcarbonyl)(2-methoxyethyl)amino]-N-[2-bromo-4-(1,1,1,2,3,3,3-heptafluoropropane-2-yl)-6-(trifluoromethyl)phenyl]benzamide (i.e., structural formula SYN001) compound 55g crude product, HPLC normalized content 56%, this step has a total of two steps of reaction yield based on 2-fluoro-3-[(2-methoxyethyl)(phenylcarbonyl)amino]benzoic acid 61.3%. The reaction formula is as follows:

[0136]

[0137] 55 g of the crude compound was recrystallized with a mixed solvent of 150 g of n-hexane and 50 g of ethyl acetate at 0-5° C. to obtain 15 g of beige crystalline dry product with an HPLC normalized content of 92%, a crystallization yield of 44.8%, and a total yield of 27.5% after crystallization in step 2.

[0138] Synthesis Example 3 (Using Ⅰ-B and Ⅱ-A Preparation Methods)

[0139] Synthesis of 2-fluoro-3-[(phenylcarbonyl)(2-methoxyethyl)amino]-N-[2-bromo-4-(1,1,1,2,3,3,3-heptafluoropropane-2-yl)-6-(trifluoromethyl)phenyl]benzamide (structural formula SYN001).

[0140] Step 1:

[0141] In a 250ml four-necked glass reaction bottle, add 100g of dichloroethane, 25g (0.20mol) of benzoic acid, and 72g (0.6mol) of thionyl chloride. Heat and reflux for reaction for 3-5 hours. Cool to room temperature, transfer the reaction solution to a 500ml rotary evaporator, decompress and desolventize to 80°C to obtain an oily liquid of benzoyl chloride. Cool to about 25°C, add 25g of new dichloroethane to dissolve and set aside.

[0142] In another 250ml four-necked glass reaction bottle, put 200g of N,N-dimethylformamide and 35g (0.20mol) of methyl 3-amino-2-fluorobenzoate, cool to 10-25°C, add 8g (0.2mol) of 60% sodium hydride in portions under nitrogen protection, control the temperature at 15-25°C, add 30g (0.21mol) of 1-bromo-2-methoxyethane dropwise in 1 hour, raise the temperature to 45-55°C and react for about 5 hours. The reaction mixture was cooled to room temperature, poured into 500 ml of ice water for precipitation, extracted with 150 g of dichloroethane, separated into layers to obtain a dichloroethane layer, dried over anhydrous magnesium sulfate, filtered to obtain a dichloroethane layer, transferred to a 500 ml four-necked glass reaction bottle, added with 24 g (0.30 mol) of pyridine, cooled to 5-25 ° C in an ice bath, and added dropwise with the above step 1 benzoyl chloride reserve solution within 1 hour, reacted at 5-25 ° C for 1-2 hours, and after the reaction was completed, 50 ml of water was added, stirred for 0.5 hour, separated into layers to obtain a solvent layer, transferred to a 500 ml rotary evaporator, and desolventized to 80 ° C to obtain an oily liquid. Add 100g methanol, 12g (0.30mol) of 10% liquid caustic soda, raise the temperature to 25-35°C, keep the temperature for about 2 hours, add 100g water, adjust the pH to 1-2 with 30% hydrochloric acid, add 300g dichloromethane for extraction, separate the layers, obtain the dichloromethane layer, transfer to a rotary evaporator and decompress to 80°C to obtain 44g of an oily liquid, which is oily after cooling, and the HPLC normalized content is 80% (the yield of these four steps is 55.4% based on benzoic acid), which is 2-fluoro-3-[(2-methoxyethyl)(phenylcarbonyl)amino]benzoic acid for standby use, and is directly used in the next step without treatment. The reaction formula is as follows:

[0143]

[0144] Step 2: Synthesis of SYN001 compound

[0145] In a 250ml four-necked glass reaction bottle, add 200g of dichloroethane, 28g (0.071mol) of 2-fluoro-3-[(2-methoxyethyl)(phenylcarbonyl)amino]benzoic acid synthesized above, and 24g (0.20mol) of thionyl chloride, and react under reflux for 3-5 hours. Then cool to room temperature, transfer the reaction solution to a 500ml rotary evaporator, desolventize to 80°C, and obtain an acyl chloride oily liquid. Cool to about 25°C, add 150g of acetonitrile to dissolve, transfer to a reaction bottle, add 27.8g (0.08mol) of 4-(1,1,1,2,3,3,3-heptafluoropropane-2-yl)-2-(trifluoromethyl)aniline raw material, and heat to reflux for 5-10 hours. The mixture was cooled to room temperature, poured into 300 ml of ice water for precipitation, extracted with 200 g of dichloroethane, washed with 50 ml of water and separated into layers to obtain a dichloroethane layer, dried over anhydrous magnesium sulfate and filtered, and desolventized to 80 ° C to obtain an oily 2-fluoro-3-[(phenylcarbonyl)(2-methoxyethyl)amino]-N-[4-(1,1,1,2,3,3,3-heptafluoropropane-2-yl)-6-(trifluoromethyl)phenyl]benzamide intermediate. 250 g of N,N-dimethylformamide was added to dissolve the mixture, and the reaction solution was transferred to a 500 ml reaction bottle, cooled to 0-25 ° C, 18 g (0.10 mol) of N-bromosuccinimide was added, and the reaction was kept warm for 5-10 hours. Pour into 500ml ice water to precipitate, extract with 200g dichloromethane, wash with 50ml water to separate the layers, obtain the dichloromethane layer, desolventize to 80°C, and obtain 58g crude product of oily 2-fluoro-3-[(phenylcarbonyl)(2-methoxyethyl)amino]-N-[2-bromo-4-(1,1,1,2,3,3,3-heptafluoropropane-2-yl)-6-(trifluoromethyl)phenyl]benzamide (i.e., structural formula SYN001), HPLC normalized content 78%, this step has a total of three steps of reaction yield based on 2-fluoro-3-[(2-methoxyethyl)(phenylcarbonyl)amino]benzoic acid 90.0%. The reaction formula is as follows:

[0146]

[0147] 58g of crude compound with HPLC normalized content of 78% was recrystallized with a mixed solvent of n-hexane 150g and ethyl acetate 50g at 0-5°C to obtain 35g of white crystalline dry product with HPLC normalized content of 96%, melting point: 179.5-180.5, single-step crystallization yield of 77.4%, and step 2 crystallization yield of 69.7%. The total yield of step 1 and step 2 combined after crystallization is 38.6%.

[0148] Synthesis Example 4 (Using Ⅰ-A and Ⅱ-A Preparation Methods)

[0149] Preparation of 2-fluoro-3-[(phenylcarbonyl)(2-ethoxyethyl)amino]-N-[2-bromo-4-(1,1,1,2,3,3,3-heptafluoropropane-2-yl)-6-(trifluoromethyl)phenyl]benzamide. (The structural formula is as follows SYN002)

[0150]

[0151] Step 1:

[0152] Similar operations and feed ratios were followed according to step 1 of Synthesis Example 1, except that 15.8 g (0.11 mol) of 1-bromo-2-methoxyethane as the raw material for the N-alkylation reaction was replaced by 17.5 g (0.11 mol) of 1-bromo-2-ethoxyethane, and other conditions remained unchanged.

[0153] 26 g of light brown crystals solidified after cooling were obtained, and the HPLC normalized content was 90%, which was 2-fluoro-3-[(2-ethoxyethyl)(phenylcarbonyl)amino]benzoic acid (0.070 mol) and was used for standby without further treatment and directly in the next step. The reaction formula is as follows:

[0154]

[0155] Step 2: Synthesis of SYN002 compound

[0156] The material obtained in step 1 (0.070 mol) was used for the synthesis in step 2, and the operation was similar to that in step 2 of synthesis example 1.

[0157] Finally, 54.3 g crude oil of 2-fluoro-3-[(phenylcarbonyl)(2-ethoxyethyl)amino]-N-[2-bromo-4-(1,1,1,2,3,3,3-heptafluoropropane-2-yl)-6-(trifluoromethyl)phenyl]benzamide (i.e., structural formula SYN002) compound was obtained, with a HPLC normalized content of 86%. The yield of this step was 92.4% based on 2-fluoro-3-[(2-ethoxyethyl)(phenylcarbonyl)amino]benzoic acid in three steps. The reaction formula is as follows:

[0158]

[0159] 54.3 g of the crude compound was recrystallized with a mixed solvent of 150 g n-hexane and 50 g ethyl acetate at 0-5°C to obtain 41 g of white crystalline dry product, HPLC normalized content 96%, melting point: 157.1-157.9, crystallization yield 84.2%, and the total yield after step 2 crystallization was 77.8%.

[0160] The NMR and mass spectrometry data are as follows:

[0161] 1H-NMR(400MHz,DMSO-d6)δ(ppm):10.54(s,1H,CONH),8.39(s,1H),7.92(s,1H),7.63-7.3 0(m,3H),7.29-7.10(m,5H),4.08-3.45(m,4H),3.44-3.32(m,2H),1.01(t,J=6.8Hz,3H). HRMS(ESI)calcd.for C 28 H 20 F 11 N2NaO3[(M+Na) + ]:743.0379[(M+Na) + ],745.0359[(M+2+Na) + ]; Found:743.0370[(M+Na) + ],745.0355[(M+2+Na) + ].

[0162] Synthesis Example 5

[0163] The same operation was carried out as in step 1 of Synthesis Example 4.

[0164] The obtained light brown crystals solidified after cooling were 26 g and had a HPLC-normalized content of 90%, which was 2-fluoro-3-[(2-ethoxyethyl)(phenylcarbonyl)amino]benzoic acid (0.070 mol).

[0165] Then use 100g of n-hexane + 20g of ethyl acetate, recrystallize at about 0-25℃ to obtain 20g of white crystalline dry product. HPLC content 98%. Melting point: 129.5-130.2℃, structural formula is as follows:

[0166]

[0167] The NMR and mass spectrometry data are as follows:

[0168] 1 H-NMR(400MHz,DMSO-d6)δ(ppm):13.27(s,1H,CO2H),7.72-7.55(m,2H),7.35-7.05(m,6 H), 4.20-3.80 (m, 2H), 3.65-3.45 (m, 2H), 3.32-3.27 (m, 2H), 0.94 (t, J = 6.8Hz, 3H, CH3).

[0169] HRMS(ESI)calcd.for C 18 H 18 FNNaO4[(M+Na) +]:354.1118; Found:354.1115.

[0170] Synthesis Example 6

[0171] The synthesis of 2-fluoro-3-[(phenylcarbonyl)(3-methoxypropyl)amino]-N-[2-bromo-4-(1,1,1,2,3,3,3-heptafluoropropane-2-yl)-6-(trifluoromethyl)phenyl]benzamide has the following structural formula: Formula SYN011.

[0172]

[0173] Step 1: According to the similar operation and feeding ratio of step 1 of Synthesis Example 1, 15.8 g (0.11 mol) of 1-bromo-2-methoxyethane as the raw material of N-alkylation reaction was replaced by 17.5 g (0.11 mol) of 1-bromo-3-methoxypropane, and other conditions were unchanged. The yield and content data of the obtained 2-fluoro-3-[(3-methoxypropyl)(phenylcarbonyl)amino]benzoic acid were similar.

[0174] Step 2: According to the similar operation and feeding ratio of step 2 of synthesis example 1, the target compound SYN011 was obtained as a white crystalline dry product with an HPLC normalized content of 96% and a melting point of 143.1-144.5°C. The obtained yield data were similar.

[0175] The NMR and mass spectrometry data are as follows:

[0176] 1 H-NMR(400MHz,DMSO-d6)δ(ppm):10.62(s,1H,CONH),8.39(s,1H),7.93(s,1H),7.63-7.30(m,3H ),7.27-7.10(m,5H),3.88-3.45(m,2H),3.42-3.32(m,2H),3.16(s,3H,CH3O),1.90-1.60(m,2H). HRMS(ESI)calcd.for C 28 H 20 F 11 N2NaO3[(M+Na) + ]:743.0379[(M+Na) + ],745.0359[(M+2+Na) + ]; Found:743.0359[(M+Na) + ],745.0343[(M+2+Na) + ].

[0177] Synthesis Example 7

[0178] The synthesis of 2-fluoro-3-{[(4-fluorophenyl)carbonyl](2-ethoxyethyl)amino}-N-[2-bromo-4-(1,1,1,2,3,3,3-heptafluoropropane-2-yl)-6-(trifluoromethyl)phenyl]benzamide has the following structural formula: Formula SYN004.

[0179]

[0180] Step 1 and Step 2: The operation and feeding ratio are similar to those of Step 1 and Step 2 of Synthesis Example 1, except that 25 g (0.20 mol) of benzoic acid is replaced by 28.6 g (0.20 mol) of p-fluorobenzoic acid.

[0181] In the N-alkylation reaction, 15.8 g (0.11 mol) of 1-bromo-2-methoxyethane as the starting material was replaced by 17.5 g (0.11 mol) of 1-bromo-2-ethoxyethane, and other conditions remained unchanged. The yield and content data of the target compound were similar.

[0182] Melting point: 168.2-169.2℃, NMR and mass spectrometry data are as follows:

[0183] 1 H-NMR(400MHz,DMSO-d6)δ(ppm):10.52(s,1H,CONH),8.38(s,1H),7.92(s,1H),7.67(dd,J=7.6Hz,and 6.8Hz,1H),7.60-7.50(m,1H),7.48-7.20(m,3H),7.18-6.95(m,2H),4.20-3 .72(m,2H),3.68-3.45(m,2H),3.42-3.32(m,2H),1.01(t,J=6.8Hz,3H,CH3).

[0184] HRMS(ESI)calcd.For C 28 H 19 F 12 N2NaO3[(M+Na) + ]:761.0285[(M+Na) + ],763.0265[(M+2+Na) + ]; Found:761.0263[(M+Na) + ],763.0248[(M+2+Na) + ].

[0185] Synthesis Example 8

[0186] Synthesis of 2-fluoro-3-{[(3,5-dichloro-4-methylphenyl)carbonyl](2-ethoxyethyl)amino}-N-[2-bromo-4-(1,1,1,2,3,3,3-heptafluoropropane-2-yl)-6-(trifluoromethyl)phenyl]benzamide. The structural formula is as follows: SYN021.

[0187]

[0188]

[0189] Step 1, Step 2: Follow the similar operation and feed ratio of Step 1 and Step 2 of Synthesis Example 1, wherein benzoyl chloride is replaced by 3,5-dichloro-4-methylbenzoyl chloride to obtain the title compound. The yield and content data of the target compound are similar. The total yield calculated with 3,5-dichloro-4-methylbenzoyl chloride is 63%, the melting point is 92.2-93.5°C, and the NMR and mass spectrometry data are as follows:

[0190] 1 H-NMR(400MHz,DMSO-d6)δ(ppm):10.52(s,1H,CONH),8.36(s,1H),7.92(s,1H),7.74(s,1H),7.61(s,1H),7 .50-7.00(m,3H),4.10-3.75(m,2H),3.72-3.50(m,2H),3.40-3.35(m,2H),2.47(s,3H),1.10-0.95(m,3H).

[0191] HRMS(ESI)calcd.for C 29 H 20 BrCl2F 11 N2NaO3[(M+Na) + ]:824.9756[(M+Na) + ],826.9736[(M+2+Na) + ]; Found:824.9444[(M+Na) + ],826.9424[(M+2+Na) + ].

[0192] Synthesis Example 9

[0193] Synthesis of 2-fluoro-3-{[(4-fluorophenyl)carbonyl](2-n-propoxyethyl)amino}-N-[2-bromo-4-(1,1,1,2,3,3,3-heptafluoropropane-2-yl)-6-(trifluoromethyl)phenyl]benzamide, the structural formula is as follows: SYN024.

[0194]

[0195] Step 1 and Step 2: The operation and feeding ratio are similar to those of Step 1 and Step 2 of Synthesis Example 1, except that 25 g (0.20 mol) of benzoic acid is replaced by 28.6 g (0.20 mol) of p-fluorobenzoic acid.

[0196] N-alkylation reaction: 15.8 g (0.11 mol) of 1-bromo-2-methoxyethane is replaced by 18.7 g (0.11 mol) of 1-bromo-2-n-propoxyethane, and other conditions and operations are similar. The yield and content data of the target compound are similar. Melting point: 156.5-156.8°C.

[0197] Synthesis Comparative Example 1

[0198] Synthesis of 2-fluoro-3-{[(3,5-dichloro-4-methylphenyl)carbonyl](methyl)amino}-N-[2-bromo-4-(1,1,1,2,3,3,3-heptafluoropropan-2-yl)-6-(trifluoromethyl)phenyl]benzamide.

[0199] According to the similar operation of Example 1, 1-3 to 1-7 of Chinese CN 102119143B, in which the benzoyl chloride in step 1-7 is replaced by the same molar amount of 3,5-dichloro-4-methylbenzoyl chloride, the title compound is obtained with a total yield of 3.8% based on the raw material 3,5-dichloro-4-methylbenzoyl chloride, melting point: 124.1-125.3°C, and the NMR and mass spectrometry data are as follows:

[0200] 1 H-NMR(400MHz,DMSO-d6)δ(ppm):10.65(s,1H,CONH),8.32(s,1H),7.88(s, 1H),7.70(s,1H),7.60(s,1H),7.38-7.30(m,3H),3.32(s,3H),2.47(s,3H).

[0201] HRMS(ESI)calcd.for C 26 H 14 BrCl2F 11 N2NaO2[(M+Na) + ]:766.9338[(M+Na) + ],768.9317[(M+2+Na) + ]; Found:766.9321[(M+Na) + ],768.9299[(M+2+Na) + ].

[0202] The structural formula and reaction formula are as follows:

[0203]

[0204] In addition to the compounds described above, the compounds in Table 2 are prepared or can be prepared by methods similar to Step 1 and Step 2 in Synthesis Example 1. The following Table 2 shows the NMR and mass spectrometry data of some compounds synthesized in Synthesis Example 1.

[0205] Table 2

[0206]

[0207]

[0208] Other compounds of the general formula (I) of the present invention can be synthesized by referring to the above method.

[0209] Preparation Example 1

[0210] The suspension concentrate sample is prepared by mixing the active ingredient, adjuvant and water according to the formula ratio (by weight) of the raw materials in Table 3 below, and then high shearing the mixture. The mixture is then sand-milled three times by a sand mill. The suspension concentrate sample is obtained after the test is qualified. The active ingredient can be any one of the compounds of the general formula (I) of the present invention, or can be mixed with existing insecticide varieties on the market.

[0211] Table 3

[0212]

[0213] Preparation Example 2

[0214] Preparation of emulsifiable concentrate samples: According to the formula ratio (by weight) of the raw materials in Table 4 below, the active ingredient, solvent, emulsifier and other auxiliary agents are heated and stirred until they are clear and transparent. The emulsifiable concentrate sample is obtained if it passes the test. The active ingredient can be selected from a compound of the general formula (I) of the present invention that is suitable for preparing emulsifiable concentrate, or it can be mixed with existing insecticide varieties on the market.

[0215] Table 4

[0216]

[0217] Biological Activity Test Example

[0218] The compounds of the general formula (I) obtained by the present invention were tested against various pests.

[0219] Compound preparation: Weigh a certain mass of the original drug with a balance (0.001 g), prepare it into a 1% mother solution with DMF, and then dilute it with distilled water containing 0.1% Tween-80 to the test concentration for use; if it is a preparation, weigh a certain mass of the preparation sample with a balance (0.001 g) according to the content of the active ingredient in the preparation, and dilute it with distilled water to the test concentration for use.

[0220] Test Example 1 Indoor biological activity determination of the compound against Plutella xylostella

[0221] The sensitive population and chlorantraniliprole-resistant population of Plutella xylostella were reared indoors on radish seedlings;

[0222] Test method: Diamondback moth activity determination: Use the dipping method, take an appropriate amount of radish leaves and soak them in the medicine for 30 seconds, then place them in a plastic petri dish with filter paper to dry naturally in the shade, and inoculate 10 2-year-old diamondback moths in each dish, and place them in an observation room at 22°C and light (16 / 8h). Observe after 2 days, touch the insect body with a brush, and if there is no reaction, it is considered dead. Repeat 3 times, and set up a blank control without adding the medicine.

[0223] Test results: The results of the activity determination of SYN001 and others against Plutella xylostella are shown in Table 5: When the test concentration is 0.2 mg / L, the activity of compounds SYN001, SYN003, SYN004, SYN006, SYN008, SYN011, SYN013, and SYN024 against the sensitive population of Plutella xylostella and the population of Plutella xylostella resistant to chlorantraniliprole all reached 100%, which is equivalent to the control sample CK02 bromofenac. At the test concentration of 0.1 mg / L, the activities of SYN001, SYN003, SYN004, SYN006, SYN008, SYN011, SYN013, SYN021, and SYN024 against the sensitive population of Plutella xylostella were all greater than ≥90%, which was equivalent to the control sample CK02 brofenoxamide. The activities of SYN003, SYN004, SYN006, SYN008, SYN011, SYN013, and SYN024 against the population of Plutella xylostella resistant to chlorantraniliprole were all 100%, which was equivalent to the control sample CK02 brofenoxamide. At the low concentration of 0.05 mg / L, the activities of SYN003, SYN004, SYN006, SYN008, SYN011, SYN013, and SYN024 against the population of Plutella xylostella resistant to chlorantraniliprole were higher than those of the control sample CK02 brofenoxamide. Surprisingly, the control sample CK05 had no activity against chlorantraniliprole-resistant populations of Plutella xylostella at all tested concentrations, indicating that the CK05 compound has cross-resistance with chlorantraniliprole.

[0224] Compounds SYN001, SYN003, SYN004, SYN006, SYN008, SYN011, SYN013, SYN021, and SYN024 have no cross-resistance to chlorantraniliprole.

[0225] Table 5 Activity test results of some compounds of general formula (I) against Plutella xylostella

[0226]

[0227] Test Example 2 Insecticidal Quick-Effect Test of Compounds

[0228] According to the method of Test Example 1, compounds SYN001, SYN003, SYN006, SYN008, SYN0011 and CK02 were selected for parallel determination of insecticidal activity against sensitive populations of Plutella xylostella. The number of dead insects was investigated 12 hours, 24 hours and 48 hours after application, and the mortality rate was calculated to compare the insecticidal rapidity. The test results are shown in Table 6:

[0229] The test results showed that compounds SYN001, SYN003, SYN006, SYN008 and SYN0011 all caused varying degrees of death 12 hours after administration, and were more effective than the control sample CK02 bromofenac.

[0230] Table 6 Results of the rapid activity test of some compounds of general formula (I) against Plutella xylostella

[0231]

[0232] Indoor biological activity determination of the compound of test example 3 against Chilo suppressalis

[0233] Activity determination of Chilo suppressalis: using the dipping method, after soaking the thin slices of wild rice stem for 30 seconds, place them in a plastic petri dish lined with filter paper to dry naturally in the shade, and inoculate 10 3rd-instar Chilo suppressalis in each dish, and observe them in a room at 26°C and light intensity (16 / 8h). Observe after 4 days, and touch the insect body with a brush. If there is no reaction, it is considered dead. Repeat 3 times, and set up a blank control without adding the agent.

[0234] The test results are shown in Table 7:

[0235] The results showed that SYN001, SYN003, SYN004, SYN006, SYN008, SYN011, SYN013 and SYN024 all had good activity at the tested concentrations, which was comparable to the control sample CK02. The control sample CK05 had no activity against Chilo suppressalis at the tested concentrations.

[0236] Table 7 Activity test results of some compounds of general formula (I) against Chilo suppressalis

[0237]

[0238]

[0239] Indoor biological activity determination of the compound of Test Example 4 against fall armyworm

[0240] Activity determination of fall armyworm: Use the dipping method, take an appropriate amount of corn leaves and soak them in the drug for 30 seconds, then place them in a plastic petri dish lined with filter paper to dry naturally in the shade, and inoculate 10 2-year-old fall armyworms in each dish, and place them in an observation room at 26°C and light (16 / 8h). Observe after 2 days, touch the insect body with a brush, and if there is no reaction, it is considered dead. Repeat 3 times, and set up a blank control without adding the drug.

[0241] The test results are shown in Table 8:

[0242] The results showed that SYN001, SYN003, SYN004, SYN006, SYN008, SYN011, SYN013 and SYN024 all had good activity at the tested concentrations, which was comparable to the control sample CK02. The control sample CK05 had no activity against the fall armyworm at the tested concentrations.

[0243] Table 8 Activity test results of some compounds of general formula (I) against fall armyworm

[0244]

[0245]

[0246] In organic molecules, due to the differences in electronegativity, size or spatial configuration of substituents, the transport properties or receptor binding of the entire molecule in organisms such as insects and plants can vary greatly, and the biological activities exhibited can also vary greatly. The transport properties of molecules and their suitability for receptor binding are unpredictable and require a lot of creative work to determine.

[0247] In the present invention, on the one hand, a heptafluoroisopropyl-containing bisamide compound of the general formula (I) obtained by molecular structure optimization has excellent insecticidal activity, especially against resistant populations, has no cross-resistance with the existing insecticide chlorantraniliprole, has good insecticidal effect and good rapidity at low doses; on the other hand, the preparation method of the compound of the general formula (I) of the present invention is simple, efficient, and easy to industrialize, and has broad application prospects in the control of insect pests in the fields of agriculture, forestry and horticulture.

[0248] The applicant declares that the present invention illustrates a heptafluoroisopropyl-containing bisamide compound and its preparation method and application through the above representative embodiments, but the present invention is not limited to the above embodiments, nor does it mean that the present invention must rely on the above embodiments to be realized. Those skilled in the art should understand that any improvement of the present invention, equivalent replacement of various raw materials of the product of the present invention, addition of auxiliary components, selection of specific methods, etc., all fall within the protection scope and disclosure scope of the present invention.

Claims

1. Compounds of general formula (I-V): in, R 1 are independently selected from H, fluoro, chloro, bromo, iodo, trifluoromethyl, methoxy, trifluoromethoxy, methyl, ethyl, methylsulfonyl, cyano or nitro; R 2 independently selected from methyl, ethyl, n-propyl, isopropyl, n-butyl or isobutyl; n is independently represented by 1 or 2.

2. The compound of general formula (I-V) according to claim 1, characterized in that The compounds of the general formula (I-V) are used in the field of synthetic insecticides.

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