Amide derivative and use thereof

Abstract

Provided are an amide derivative 5-chloro-N-(2-fluoro-3-(2-iodo-4-(perfluoropropane-2-yl)-6-(trifluoromethyl)phenyl)carbamoyl)phenyl)thiophene-2-carboxamide and the use thereof in killing, preventing and controlling agricultural and forestry pests, particularly pests with chewing mouthparts, such as plutella xylostella, beet armyworm, and cotton bollworm. The compound is safe for honey bees.

Description

An amide derivative and its application Technical Field

[0001] This invention relates to amide derivatives, specifically to an amide derivative and its applications. It belongs to the field of insecticide preparation technology. Background Technology

[0002] Insecticides play a vital role in pest control in my country's agriculture, forestry, and public health sectors. Organophosphates, carbamates, pyrethroids, neonicotinoids, and macrolides were once widely used; however, due to increasing environmental concerns, their inherent toxicity, pest resistance, and ecotoxicity, these insecticides have been restricted or phased out. In recent years, diamide insecticides, led by flubendiamide, have gained global popularity due to their excellent insecticidal activity and lack of cross-resistance with traditional insecticides. However, over time, resistance to diamide insecticides has become a significant issue, and safety concerns have gradually emerged. Recent domestic and international monitoring data show that they exhibit medium to high levels of resistance in populations of rice stem borer, rice leaf roller, beet armyworm, and diamondback moth. Products such as flubendiamide, chlorantraniliprole, bromocyanamide, tetrachlorantraniliprole, and flubendiamide have successively revealed safety issues, including serious harm to aquatic invertebrates, causing metamorphosis in silkworms, and affecting the flight ability of bees. The pesticide market urgently needs to develop new, highly effective, low-toxicity, and safe insecticides for pest control.

[0003] Brofenoxam, a novel diamide insecticide first registered globally in 2019, was successfully developed through structural optimization, using flubendiamide as a lead agent. Its chemical structure is similar to chlorantraniliprole and flubendiamide, and its site of action overlaps with macrolides such as abamectin, but its mode of action differs. It remains effective against pests resistant to macrolides and fipronil. Brofenoxam is an allosteric regulator of GABA-gated chloride channels (also known as ionic GABA receptors). It primarily acts on a unique binding site on this ion channel, inhibiting chloride ion translocation into the cell, causing insect over-excitation or spasms, thus exhibiting rapid insecticidal activity. It is mainly used to control lepidopteran, coleopteran, tsanoptera, termites, and mosquitoes and flies on leafy vegetables, perennial crops, and cereals. Brombutamide currently exhibits insecticidal activity far superior to traditional insecticides due to its special structure and unique mechanism of action. As a novel diamide insecticide, it has no cross-resistance with existing insecticides and is safe to use. In recent years, the sales volume of this product has been gradually increasing, and it is expected to replace chlorantraniliprole, the current "king" of insecticides, in the future.

[0004] Currently, pesticide application is a crucial means of preventing and controlling plant diseases and pests in agricultural production. However, with the increasing usage, scope, and duration of existing pesticides, as well as the improper use of some pesticides, some pests are gradually developing significant resistance to common pesticides, making pesticide control increasingly difficult. The emergence of resistance to bromuconazole is also inevitable in the future. Developing and researching innovative pesticides is currently an effective way to address the problem of pest resistance. Therefore, developing new, highly effective, low-toxicity, and safe insecticides for pest control is of great significance in the agricultural field and is a hot topic in innovative pesticide research and development. Summary of the Invention

[0005] The purpose of this invention is to overcome the shortcomings of the prior art described above. This invention provides an amide derivative and its application.

[0006] To achieve the above objectives, the present invention adopts the following technical solution:

[0007] 1. An amide derivative or a pesticide-acceptable salt or solvate, said amide derivative being named 5-chloro-N-(2-fluoro-3-(2-iodo-4-(perfluoropropane-2-yl)-6-(trifluoromethyl)phenyl)carbamoyl)phenyl)thiophene-2-carboxamide, with the molecular formula C1 22 H9ClF 11 IN2O2S has the following chemical structural formula:

[0008] 2. A pharmaceutical composition comprising one of the aforementioned amide derivatives or a pesticide-acceptable salt or solvate.

[0009] 3. The application of the aforementioned amide derivative or pesticide-acceptable salt or solvate in the preparation of insecticides.

[0010] As one of the preferred technical solutions, the insecticide is used to control agricultural and forestry pests.

[0011] As one of the preferred technical solutions, the insecticide is used to control chewing mouthpart pests.

[0012] As a further preferred technical solution, the chewing mouthpart pests are selected from: larvae of Lepidoptera insects, adults or nymphs of Orthoptera insects, adults or larvae of Coleoptera insects, and larvae of Hymenoptera insects.

[0013] As a further preferred technical solution, the chewing mouthpart pests are selected from: diamondback moth, beet armyworm, cotton bollworm, and cotton bollworm.

[0014] 4. Application of the aforementioned pharmaceutical composition in the preparation of insecticides.

[0015] As one of the preferred technical solutions, the insecticide is used to control agricultural and forestry pests.

[0016] As one of the preferred technical solutions, the insecticide is used to control chewing mouthpart pests.

[0017] As a further preferred technical solution, the chewing mouthpart pests are selected from: larvae of Lepidoptera insects, adults or nymphs of Orthoptera insects, adults or larvae of Coleoptera insects, and larvae of Hymenoptera insects.

[0018] As a further preferred technical solution, the chewing mouthpart pests are selected from: diamondback moth, beet armyworm, cotton bollworm, and cotton bollworm.

[0019] 5. An insecticide whose active ingredient is an amide derivative or a pesticide-acceptable salt or solvate as described above.

[0020] 6. An insecticide comprising the aforementioned pharmaceutical composition.

[0021] The beneficial effects of this invention are:

[0022] This invention obtained a new compound, CCXN-7-021, which can be used for the preparation of insecticides, through screening. The compound is 5-chloro-N-(2-fluoro-3-(2-iodo-4-(perfluoropropane-2-yl)-6-(trifluoromethyl)phenyl)carbamoyl)phenyl)thiophene-2-carboxamide.

[0023] The applicant has demonstrated through experiments that the novel amide derivative CCXN-7-021 in this invention exhibits excellent sustained and rapid efficacy in controlling agricultural and forestry pests, particularly chewing pests such as diamondback moth, beet armyworm, and cotton bollworm. Based on current indoor toxicity testing results, the compound CCXN-7-021 demonstrates superior efficacy against agricultural and forestry pests such as diamondback moth, beet armyworm, and cotton bollworm compared to the commercially available bromfenac. Its efficacy against diamondback moth is 16 times that of bromfenac, against beet armyworm is 10 times that of bromfenac, and its efficacy against cotton bollworm is comparable to bromfenac. It is also significantly superior to compounds with similar structures (Comparative Example 1), exhibiting 380 times the efficacy against diamondback moth, 150 times the efficacy against beet armyworm, and approximately 10 times the efficacy against cotton bollworm. CCXN-7-021, with its unique structure and mechanism of action, is unlikely to develop cross-resistance with traditional m-diamide compounds.

[0024] Furthermore, CCXN-7-021 exhibits excellent safety in mammals; toxicological test data show that the acute oral LD50 in rats is [not specified]. 50With a concentration >5000 mg / kg, CCXN-7-021 is classified as only slightly toxic according to pesticide toxicity grading standards, comparable to the marketed product bromfenac. Furthermore, environmental safety evaluation tests show that CCXN-7-021 is moderately toxic to bees, while the marketed bromfenac and similar compounds (Comparative Example 1) are all highly toxic to bees. Therefore, CCXN-7-021 is safer for bees than bromfenac and similar compounds (Comparative Example 1). Currently, to protect ecosystem health and control the potential adverse effects of high-risk pesticides on environmental organisms from the source, Europe and the United States have proposed comprehensive pesticide biosafety evaluation systems for bees. my country's Ministry of Environmental Protection and Ministry of Agriculture have also included pesticide biotoxicity and safety evaluation for bees as important components of pesticide registration management and environmental safety management for pesticide use. Against this backdrop and trend, the future application scenarios for CCXN-7-021 will be far greater than those for bromfenac.

[0025] In conclusion, CCXN-7-021 has enormous market potential in the field of agricultural and forestry pest control, and has very good promotion and application value and prospects. Attached Figure Description

[0026] Figure 1 shows the proton NMR spectrum of the compounds in the examples. Detailed Implementation

[0027] The present invention will be further described below with reference to the accompanying drawings and embodiments. It should be noted that the following description is only for explaining the present invention and does not limit its content.

[0028] Example 1 Compound CCXN-7-021

[0029] The chemical structural formula is as follows:

[0030] The preparation method is as follows:

[0031] 5 g (15.2 mmol) of 2-trifluoromethyl-4-(heptafluoroisopropyl)aniline was placed in a 50 mL three-necked flask, and 15 mL of anhydrous ethanol was added. Stirring was started. The temperature was controlled in an ice-water bath. 1.58 g of 98% concentrated sulfuric acid was added, which was exothermic. After addition, the temperature was slowly lowered to below 20 °C. Then, 3.76 g (16.7 mmol) of N-iodosuccinimide was added, and the mixture was transferred to an oil bath. The oil bath was heated to 40 °C and stirred for about 3 hours. TLC monitoring showed that the petroleum ether:ethyl acetate ratio was 10:1 (volume ratio), indicating that the reactants had largely reacted. The pH was adjusted to neutral with 4 M sodium hydroxide aqueous solution, and 20 mL of ethyl acetate was added for extraction. The mixture was stirred and separated, and extracted three times. The combined organic phases were washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure to obtain approximately 7 g of oily intermediate 1 (4-heptafluoroisopropyl-2-iodo-6-(trifluoromethyl)aniline). The crude product was added to the next step.

[0032] In a 50 mL three-necked flask, 3.5 g (18.9 mmol) of 2-fluoro-3-nitrobenzoic acid, 12 mL of toluene, and 0.05 mL of dimethylformamide were added. Thionyl chloride (2.8 g, 23.6 mmol) was added with stirring at room temperature. The mixture was then heated to reflux and stirred for 2 h. The reaction was monitored by TLC (the reaction solution was mixed with methanol and spotted using a dichloromethane:methanol ratio of 20:1, v / v). The reaction proceeded completely. The solvent and thionyl chloride were removed by vacuum concentration. Two 10 mL solutions of dichloromethane were added and dried twice before being transferred to a 50 mL three-necked flask. 14 mL of 1,3-dimethyl-2-imidazolinone was added, followed by stirring. (4-heptafluoroisopropyl-2-iodo-6-(trifluoromethyl)aniline)iodointermediate 1 (7 g, crude product, 15.2 mmol) was added. The mixture was then stirred overnight in an oil bath at 100 °C. TLC analysis of the reaction (petroleum ether:ethyl acetate = 4:1, v / v) showed that both starting materials had small amounts remaining. The reaction was stopped, and 16 mL of water was added to quench the reaction mixture. Then, 20 mL of ethyl acetate was added, the mixture was stirred, allowed to stand, and separated. The aqueous phase was extracted with 10 mL of ethyl acetate. The combined organic phases were washed twice with 50 mL of saturated brine. The solution was dried over anhydrous sodium sulfate. The product was concentrated and purified by silica gel column chromatography (petroleum ether / ethyl acetate = 4:1) to give 2.5.9 g of a white solid (2-fluoro-N-(2-iodo-4-(perfluoropropane-2-yl)-6-(trifluoromethyl)phenyl)-3-nitrobenzamide) iodinated intermediate, yield 62%.

[0033] (2-fluoro-N-(2-iodo-4-(perfluoropropane-2-yl)-6-(trifluoromethyl)phenyl)-3-nitrobenzamide)iodointermediate 2 (5.9 g, 9.5 mmol) was placed in a 100 mL three-necked flask. 36 mL of anhydrous ethanol was added, followed by stirring and the addition of anhydrous stannous chloride (7 g, 3.70 mmol). The temperature was then lowered to 0 °C, and 6.16 g of concentrated hydrochloric acid was added directly. After the addition was complete, the mixture was stirred at 60 °C for 2 h. The reaction proceeded to TLC. The pH was adjusted to 9–10 with 4 M sodium hydroxide, resulting in the precipitation of a large amount of solid. The solid was directly filtered and washed with ethyl acetate. The mother liquor was collected, and 30 mL of ethyl acetate and 10 mL of water were added. The mixture was stirred and separated. The aqueous phase was extracted with 10 mL of ethyl acetate. The combined organic phases were washed with 10 mL of saturated brine, dried over anhydrous sodium sulfate, and concentrated to obtain 3 g of a brown solid. The product was slurried using 10 ml of petroleum ether:ethyl acetate in a 4:1 (volume ratio) solution for 2 hours to obtain a pure product. The product was then placed in a 45°C forced-air drying oven to obtain 2.5 g of a white solid (3-amino-2-fluoro-N-(2-iodo-4-(perfluoropropane-2-yl)-6-(trifluoromethyl)phenyl)benzamide)iodo-common intermediate, with a yield of 44.4%.

[0034] 2-Chlorothiophene-5-carboxylic acid (1 g, 6.2 mmol) was added to 10 mL of dichloromethane, followed by thionyl chloride (2 g, 16.8 mmol) and 0.15 mL of dimethylformamide. The mixture was heated to 45 °C and reacted for 4 h. A sample was taken, and methanol was added and the mixture was shaken. TLC (petroleum ether: ethyl acetate = 4:1, volume ratio) showed that the reaction of the starting material was complete. The mixture was concentrated under reduced pressure at 45 °C, and a solid gradually precipitated out. 5 mL of dichloromethane was added and the mixture was dried to obtain a pale yellow semi-solid, which was dissolved in 3 mL of toluene for later use.

[0035] (3-amino-2-fluoro-N-(2-iodo-4-(perfluoropropane-2-yl)-6-(trifluoromethyl)phenyl)benzamide)iodo-common intermediate (3 g, 5.1 mmol) was added to 10 mL of toluene, followed by the above-mentioned 2-chlorothiophene-5-carboxyl chloride, and then 0.15 mL of dimethylformamide. The mixture was heated to 100 °C and reacted overnight. A sample was taken, and ethyl acetate and water were added and shaken. TLC (petroleum ether:ethyl acetate = 1:1, volume ratio) showed that the reaction of the starting material was complete. The mixture was then cooled to room temperature. Toluene was evaporated at 50°C, and a mixture of dichloromethane / methanol / water (volume ratio 20 / 1 / 10, 60 ml) was added and stirred for 3 hours. The mixture was filtered, and the filter cake was dried to obtain 1.5 g of a white solid, 5-chloro-N-(2-fluoro-3-(2-iodo-4-(perfluoropropane-2-yl)-6-(trifluoromethyl)phenyl)carbamoyl)phenyl)thiophene-2-carboxamide, with a yield of 40% and a purity of 98.72%.

[0036] The hydrogen spectrum of the product is shown in Figure 1.

[0037] 1 H NMR (400MHz, CDCl3) δ8.63–8.50(m,1H),8.36(s,1H),8.20(d,J=11.6Hz,1H),7.95(s,1H) ,7.91–7.81(m,2H),7.47(d,J=4.0Hz,1H),7.36(t,J=8.1Hz,1H),7.00(d,J=4.0Hz,1H).C 22 H9ClF 11 IN₂O₂S, [M+Na] + =758.8834

[0038] Comparative Example 1

[0039] Patent application CN114805294A (2891535-03-6)

[0040] The chemical structural formula is as follows:

[0041] The preparation method is as follows:

[0042] 130 g of 2-trifluoromethyl-4-(heptafluoroisopropyl)aniline was added to a 500 mL three-necked flask, followed by 200 mL of DMF. 86 g of NBS was added in three batches over 30 min, and the mixture was heated to 60 °C and stirred for 2 h. TLC monitoring showed that the reaction mixture (PE:EA = 10:1) was complete. The reaction solution was poured into 2 L of water, and extracted twice with 1 L of ethyl acetate. The combined organic phases were washed with 200 mL of 10% sodium thiosulfate aqueous solution. After separation, the organic phase was dried over anhydrous sodium sulfate. Rotary evaporation yielded 130 g of an orange oily product (2-bromo-4-(perfluoropropane-2-yl)-6-(trifluoromethyl)aniline) brominated intermediate 1, with a small amount of solid precipitating. The yield was 81%, and no further purification was performed; the product was then added to the next step.

[0043] 72 g of 2-fluoro-3-nitrobenzoic acid, 100 mL of toluene, and 1 mL of DMF (N,N-dimethylformamide) were added to a 500 mL three-necked flask. 68 g of thionyl chloride was added under stirring at room temperature, followed by reflux in an oil bath for 2 hours. The reaction was monitored by TLC (after adding methanol to the reaction solution and shaking, the mixture was spotted using a DCM:methanol ratio of 10:1, v / v). The reaction of 2-fluoro-3-nitrobenzoic acid was complete. Toluene was removed by rotary evaporation at 50 °C under reduced pressure. 200 mL of DMI (1,3-dimethyl-2-imidazolinone) and 130 g of (2-bromo-4-(perfluoropropane-2-yl)-6-(trifluoromethyl)aniline)bromo intermediate were added to the resulting oil. The mixture was stirred overnight in an oil bath at 100 °C. The reaction was monitored by TLC (PE:EA = 4:1, v / v). The reaction solution was poured into 600 mL of water, and extracted with 400 mL of EA (400 mL x 3). The organic phases were combined and dried over anhydrous sodium sulfate. The mixture was then subjected to rotary evaporation under reduced pressure. During this process, a large amount of solid precipitated. The solid was evaporated until only a small amount of solvent remained. The solid was then filtered to give 2,120 g of a white product (N-(2-bromo-4-(perfluoropropane-2-yl)-6-(trifluoromethyl)phenyl)-2-fluoro-3-nitrobenzamide) brominated intermediate, yield 65.4%.

[0044] In a 1L reaction flask, 100g of (N-(2-bromo-4-(perfluoropropane-2-yl)-6-(trifluoromethyl)phenyl)-2-fluoro-3-nitrobenzamide)bromointermediate 2, 300mL of ethanol, and 50mL of hydrochloric acid were added. After stirring for 10min, 96g of anhydrous stannous chloride was added, and the mixture was heated to 60℃ and stirred for 2h. TLC monitoring showed a PE:EA ratio of 4:1 (volume ratio). After the reactants had reacted completely, the ethanol was removed by rotary evaporation. The pH was adjusted to 10 with a 10% sodium hydroxide aqueous solution, resulting in the precipitation of a large amount of off-white solid. 300mL*3 of EA was added to extract the aqueous phase (with the solids). The upper organic phases were combined, dried with anhydrous magnesium sulfate, and then rotary evaporated to obtain a yellow to brown oily product, 60g of (3-amino-N-(2-bromo-4-(perfluoropropane-2-yl)-6-(trifluoromethyl)phenyl)-2-fluorobenzamide)bromointermediate 3, with a yield of 63%. No further purification was performed; proceed directly to the next step.

[0045] Under ice-water bath conditions, 237 g of sulfuric acid was added to a 500 mL three-necked flask. While stirring, 350 g of (3-amino-N-(2-bromo-4-(perfluoropropane-2-yl)-6-(trifluoromethyl)phenyl)-2-fluorobenzamide) brominated intermediate was added in three portions. After stirring for 10 min, the temperature of the reaction solution was maintained below 40 °C, and 41 mL of 37% formaldehyde aqueous solution was added dropwise. After the addition was complete, the mixture was stirred at 40 °C for 2 h. The petroleum ether (PE): ethyl acetate (EA) ratio was monitored by TLC to be 4:1 (volume ratio), and no raw material remained. The reaction solution was poured into 300 mL of ice water, and the pH was adjusted to 10 with 4M sodium hydroxide aqueous solution. The aqueous phase was then extracted with 300 mL of ethyl acetate three times. The organic phases were combined, dried with anhydrous magnesium sulfate for 1.5 h, filtered, and the organic phase was evaporated to dryness. The sample was mixed with 70 g of 100-200 mesh silica gel and purified by column chromatography. The purified sample was passed through a column (250 g of 200-300 mesh silica gel) with a polar PE:EA ratio of 20:1-10:1 (volume ratio) to obtain 27 g of off-white powder (N-(2-bromo-4-(perfluoropropane-2-yl)-6-(trifluoromethyl)phenyl)-2-fluoro-3-(methylamino)benzamide), with a yield of 53%.

[0046] Take 0.8g of 2-chlorothiophene-5-carboxylic acid, add 10ml of dichloromethane (DCM), 0.8g of thionyl chloride, and 0.15ml of DMF. Set the oil bath to 45℃ and react for 4h. Take a sample, add methanol and shake. TLC (PE:EA = 4:1, volume ratio) shows that the reaction of the raw materials is complete. Concentrate under reduced pressure at 45℃ and a solid gradually precipitates. Add 5mL of DCM to dry slightly to obtain a pale yellow semi-solid. Add 2mL of toluene as reaction solution A.

[0047] Take 2g of (3-amino-N-(2-bromo-4-(perfluoropropane-2-yl)-6-(trifluoromethyl)phenyl)-2-fluorobenzamide) brominated intermediate 3, add 10ml of toluene and stir magnetically. The solid is insoluble. Drop it into reaction solution A, add 0.15ml of N,N-dimethylformamide (DMF), heat to 100℃, react for 2h, take a sample, add EA and water and shake. TLC (PE:EA = 1:1, volume ratio) shows that the reaction of the raw materials is complete, and stop heating. Upon cooling, a solid precipitated out. The solid was filtered, and 10 ml of DCM:MEOH = 20:1 (volume ratio) was added. The mixture was stirred for 0.5 h, filtered again, and a white powder was obtained. The powder was washed with water (10 ml x 3 times) and dried overnight at 40 °C under forced air to obtain 1.2 g of a white solid N-(3-((2-bromo-4-(perfluoropropane-2-yl)-6-(trifluoromethyl)phenyl)carbamoyl)-2-fluorophenyl)-5-chlorothiophene-2-carboxamide. Yield: 47%, Purity: 99.23%.

[0048] 1H NMR (600MHz, CDCl3) δ8.57(td,J=8.0,1.6Hz,1H),8.14(d,J=14.1Hz,2H),7.93(s,1H),7.87( dd,J=11.1,3.6Hz,2H),7.47(d,J=4.0Hz,1H),7.36(t,J=8.0Hz,1H),7.00(d,J=4.0Hz,1H).C 22 H9BrClF 11 N₂O₂S, [M+H] + =690.9128

[0049] Comparative Example 2

[0050] Compound CCXN-7-002

[0051] The preparation method is as follows:

[0052] The preparation method of the brominated common intermediate is the same as that of Comparative Example 1.

[0053] Add 2g of 2-chlorothiophene-5-carboxylic acid to 20ml of DCM, add 4g of thionyl chloride and 0.15ml of DMF, heat to 45℃ and react for 4h. Take a sample, add methanol and shake. TLC (PE:EA=4:1, volume ratio) shows that the reaction of the raw materials is complete. Concentrate under reduced pressure at 45℃ and a solid gradually precipitates. Add 10mL of DCM and dry slightly to obtain a pale yellow semi-solid, which is dissolved in 5mL of toluene for later use.

[0054] 5g of the (N-(2-bromo-4-(perfluoropropane-2-yl)-6-(trifluoromethyl)phenyl)-2-fluoro-3-(methylamino)benzamide) brominated common intermediate was added to 20ml of toluene, followed by the above-mentioned 2-chlorothiophene-5-carboxyl chloride, and 0.15ml of DMF. The mixture was heated to 100℃ and reacted overnight. A sample was taken, and EA and water were added and shaken. TLC (PE:EA = 1:1) showed that the reaction of the starting material was complete. The mixture was then cooled to room temperature. Toluene was evaporated at 50℃, and a mixture of DCM / methanol / water (volume ratio 20 / 1 / 10, 60 mL) was added and stirred for 3 hours. The mixture was filtered, and the filter cake was dried to obtain 2.5 g of a white solid N-(3-((2-bromo-4-(perfluoropropane-2-yl)-6-(trifluoromethyl)phenyl)carbamoyl)-2-fluorophenyl)-5-chloro-N-methylthiophene-2-carboxamide, yield: 39.7%, purity: 98.83%.

[0055] 1H NMR (400MHz, CDCl3) δ8.23(t,J=6.7Hz,1H),8.17(d,J=15.6Hz,2H),7.91(s,1H),7.59(td,J=7. 7,1.5Hz,1H),7.43(t,J=7.9Hz,1H),6.79(d,J=3.8Hz,1H),6.70(d,J=4.1Hz,1H),3.47(s,3H).C 23 H 11 BrClF 11 N₂O₂S, [M+H] + =704.9286

[0056] Comparative Example 3

[0057] Compound CCXN-7-008

[0058] The preparation method is as follows:

[0059] The preparation method of the (N-(2-bromo-4-(perfluoropropane-2-yl)-6-(trifluoromethyl)phenyl)-2-fluoro-3-(methylamino)benzamide) brominated common intermediate is the same as that of Comparative Example 1.

[0060] Add 2g of 1-naphthic acid, 10ml of toluene, and 0.15ml of DMF to a 50ml reaction tube, then add 4.14g of thionyl chloride dropwise. Heat to 100℃ and react for 4h. Take a sample, add methanol and shake. TLC detection shows that the 1-naphthic acid reaction is complete (DCM:MEOH = 10:1, volume ratio). Rotate the solvent at 45-55℃ to dryness, then add 5ml of toluene to dissolve and set aside.

[0061] Take a 50 mL reaction tube, add 3 g of (N-(2-bromo-4-(perfluoropropane-2-yl)-6-(trifluoromethyl)phenyl)-2-fluoro-3-(methylamino)benzamide) bromo-common intermediate, 20 mL of toluene, and add the above-mentioned 1-naphthoyl chloride while stirring. A small amount of bubbles are generated. The temperature is raised to 100 °C and reacted for 3 h. TLC detection (PE:EA = 4:1, volume ratio) shows that the starting material has basically reacted completely. Stop the reaction and let the temperature drop to room temperature. Toluene is evaporated at 50 °C, and DCM / methanol / water (volume ratio 20 / 1 / 10, 60 mL) is stirred for 3 h. Filter, and dry the filter cake to obtain 2.4 g of off-white solid N-(3-((2-bromo-4-(perfluoropropane-2-yl)-6-(trifluoromethyl)phenyl)carbamoyl)-2-fluorophenyl)-N-methyl-1-naphthoylamide, yield: 64%, purity: 98.49%.

[0062] 1H NMR (400MHz, DMSO) δ10.71(d,J=139.7Hz,1H),8.42(d,J=29.1Hz,1H),8.22–7.74(m,4.75H),7.67 (s,1H),7.57-7.51(m,2.5H),7.45–7.22(m,2.2H),7.09(s,0.7H),3.50(s,2.2H),3.10(s,0.8H).C 29 H 16 BrF 11 N₂O₂, [M+H] + =715.0379.

[0063] Comparative Example 4

[0064] Compound CCXN-7-009

[0065] The preparation method is as follows:

[0066] The preparation method of the (N-(2-bromo-4-(perfluoropropane-2-yl)-6-(trifluoromethyl)phenyl)-2-fluoro-3-(methylamino)benzamide) brominated common intermediate is the same as that of Comparative Example 1.

[0067] Add 2g of 2-naphthic acid, 10ml of toluene, and 0.15ml of DMF to a 50ml reaction tube. Add 4.14g of thionyl chloride dropwise while stirring. Heat to 100℃ and react for 4h. Take a sample, add methanol and shake. Detect the complete reaction of 2-naphthic acid by TLC (DCM:MEOH = 10:1, volume ratio). After evaporating the solvent at 45℃, add 5ml of toluene to dissolve the solvent and set aside.

[0068] Take a 50 mL reaction tube, add 3 g of (N-(2-bromo-4-(perfluoropropane-2-yl)-6-(trifluoromethyl)phenyl)-2-fluoro-3-(methylamino)benzamide) bromo-common intermediate, 20 mL of toluene, and add the above-mentioned 2-naphthoyl chloride dropwise with stirring. Heat to 100 °C and react for 6 h. TLC analysis (PE:EA = 4:1, volume ratio) showed that the starting material had basically reacted, and the reaction was stopped. Toluene was evaporated at 50 °C, and a slurry of DCM / methanol / water (volume ratio 20 / 1 / 10, 60 mL) was stirred for 3 h. The mixture was filtered, and the filter cake was dried to obtain 1.5 g of a white solid N-(3-((2-bromo-4-(perfluoropropane-2-yl)-6-(trifluoromethyl)phenyl)carbamoyl)-2-fluorophenyl)-N-methyl-2-naphthoylamide, yield: 40%, purity: 98.26%.

[0069] 1H NMR (400MHz, DMSO) δ10.65(s,1H),8.40(s,1H),7.94(s,2H),7.87(d,J=7.1Hz,2H),7.81(d,J=6.7H z,1H),7.69(t,J=6.6Hz,1H),7.58–7.46(m,3H),7.42(s,1H),7.30(d,J=6.6Hz,1H),3.42(s,3H).C 29 H 16 BrF 11 N₂O₂, [M+H] + =715.0246

[0070] Comparative Example 5

[0071] Compound CCXN-7-010

[0072] The preparation method is as follows:

[0073] The preparation method of the (3-amino-2-fluoro-N-(2-iodo-4-(perfluoropropane-2-yl)-6-(trifluoromethyl)phenyl)benzamide)iodo-common intermediate is the same as in Example 1.

[0074] Add 2g of 1-naphthic acid, 5ml of toluene, and 0.15ml of DMF to a 50ml reaction tube. Add 4.14g of thionyl chloride dropwise. Heat to 100℃ and react for 3 hours. Take a sample, add methanol and shake. TLC (DCM:MEOH = 10:1, volume ratio) to confirm the complete reaction of 1-naphthic acid. Rotate dry at 45℃, then dissolve in 5ml of toluene for later use.

[0075] Take a 50 ml reaction tube, add 5 g of the (3-amino-2-fluoro-N-(2-iodo-4-(perfluoropropane-2-yl)-6-(trifluoromethyl)phenyl)benzamide)iodo-common intermediate, 20 ml of toluene, and the above-mentioned 1-naphthoyl chloride. Heat to 100 °C and react for 3 h. TLC detection (PE:EA = 4:1, volume ratio) showed that the starting material had basically reacted. Stop the reaction, evaporate the toluene at 50 °C, add DCM / methanol / water (volume ratio 20 / 1 / 10, 60 ml), and stir for 3 h. Filter, and dry the filter cake to obtain 3 g of off-white solid N-(2-fluoro-3-((2-iodo-4-(perfluoropropane-2-yl)-6-(trifluoromethyl)phenyl)carbamoyl)phenyl)-1-naphthoylamide, yield: 47%, purity: 97.81%.

[0076] 1H NMR (400MHz, DMSO) δ10.79(s,1H),10.57(s,1H),8.52(s,1H),8.36–8.25(m,1H),8.11(d,J=8.3Hz,1H),8 .04(dd,J=6.5,2.8Hz,2H),7.97(s,1H),7.84(d,J=6.9Hz,1H),7.69–7.56(m,4H),7.45(t,J=7.9Hz,1H).C 28 H 14 F 11 IN₂O₂, [M+H] + =746.9964

[0077] Comparative Example 6

[0078] Compound CCXN-7-011

[0079] The preparation method is as follows:

[0080] The preparation method of the (3-amino-2-fluoro-N-(2-iodo-4-(perfluoropropane-2-yl)-6-(trifluoromethyl)phenyl)benzamide)iodo-common intermediate is the same as in Example 1.

[0081] Add 2g of 2-naphthic acid, 5ml of toluene, and 0.15ml of DMF to a 50ml reaction tube. Add 4.14g of thionyl chloride dropwise. Heat to 100℃ and react for 3 hours. Take a sample, add methanol and shake. TLC (DCM:MEOH = 10:1, volume ratio) to confirm the complete reaction of 1-naphthic acid. Rotate dry at 45℃, then dissolve in 5ml of toluene for later use.

[0082] Take a 50 ml reaction tube, add 5 g of the (3-amino-2-fluoro-N-(2-iodo-4-(perfluoropropane-2-yl)-6-(trifluoromethyl)phenyl)benzamide)iodo-common intermediate, 20 ml of toluene, and the above-mentioned 2-naphthoyl chloride. Heat to 100 °C and react for 3 h. TLC detection (PE:EA = 4:1, volume ratio) showed that the starting material had basically reacted. Stop the reaction, evaporate the toluene at 50 °C, add DCM / methanol / water (volume ratio 20 / 1 / 10, 60 ml), and stir for 3 h. Filter, and dry the filter cake to obtain 1.7 g of off-white solid N-(2-fluoro-3-((2-iodo-4-(perfluoropropane-2-yl)-6-(trifluoromethyl)phenyl)carbamoyl)phenyl)-2-naphthoylamide, yield: 27%, purity: 99.52%.

[0083] 1H NMR (400MHz, DMSO) δ10.79(s,1H),10.48(s,1H),8.67(s,1H),8.52(s,1H),8.13–8.09(m,1H),8.08(s,2 H),8.04(d,J=7.5Hz,1H),7.97(s,1H),7.91(t,J=6.9Hz,1H),7.71–7.58(m,3H),7.44(t,J=7.8Hz,1H).C 28 H 14 F 11 IN₂O₂, [M+H] + =746.9996

[0084] Test case

[0085] The applicant conducted toxicological studies on the compounds obtained in the examples and conducted efficacy tests on the compounds obtained in the examples and comparative examples for controlling agricultural and forestry pests.

[0086] 1. Toxicological studies

[0087] Rats were administered CCXN-7-021 suspension by gavage at doses of 500 mg / kg and 5000 mg / kg, respectively, once per dose. After two days of continuous observation, no significant abnormalities were observed in the rats. At the end of the observation period, surviving rats underwent necropsy, and no gross lesions were found in the major organs. LD 50 >5000 mg / kg. According to the acute oral toxicity grading standard in the "Regulations on Pesticide Registration Data", the acute oral toxicity of CCXN-7-021 rats is classified as slightly toxic.

[0088] As shown in Table 1, the toxicological data of compound CCXN-7-021 obtained in Example 1 are comparable to those of the commercially available product bromonitrile diphenyl amide (purchased from Dezhou Hanhua Pharmaceutical Chemical Co., Ltd.), and both are classified as slightly toxic according to the pesticide product toxicity classification standards.

[0089] Table 1. Comparison of Toxicological Data

[0090] 2. Pest control efficacy test in agriculture and forestry

[0091] The toxicity of the following compounds against diamondback moth, beet armyworm, and cotton bollworm was evaluated in indoor experiments using the leaf-dipping method. Reference standard: Agricultural Industry Standard of the People's Republic of China, "Guidelines for Indoor Bioassay Testing of Pesticides - Insecticides Part 14: Leaf Dipping Method" (NY / T 1154.14-2008).

[0092] As shown in Table 2, the compound CCXN-7-021 obtained in Example 1 exhibits superior efficacy against agricultural and forestry pests such as diamondback moth, beet armyworm, and cotton bollworm compared to the commercially available bromutsulfuron-methyl. Its efficacy against diamondback moth is 16 times that of bromutsulfuron-methyl, against beet armyworm is 10 times that of bromutsulfuron-methyl, and its efficacy against cotton bollworm is comparable to that of bromutsulfuron-methyl. It is significantly superior to Comparative Example 1, exhibiting 380 times the efficacy against diamondback moth, 150 times the efficacy against beet armyworm, and approximately 10 times the efficacy against cotton bollworm.

[0093] Table 2. Control efficacy tests for agricultural and forestry pests

[0094] 3. Environmental safety assessment test

[0095] Experimental objective: To preliminarily determine the oral toxicity of the following compounds to bees.

[0096] Experimental target: Italian worker bee (Apis mellifera).

[0097] Test reference methods and target toxicity reference standards: GB / T 31270.10-2014 "Test Guidelines for Environmental Safety Evaluation of Chemical Pesticides Part 10: Acute Toxicity Tests for Honeybees" (Table 3).

[0098] Table 3. Classification of pesticide toxicity levels to bees

[0099] Table 4 shows that the environmental safety evaluation test results of compound CCXN-7-021 obtained in Example 1 indicate that its toxicity to bees is moderate. Brombutamide is classified as highly toxic to bees. Comparative Example 1 is also classified as highly toxic to bees.

[0100] Table 4. Environmental Safety Assessment Test

[0101] While the specific embodiments of the present invention have been described above in conjunction with the accompanying drawings, this is not intended to limit the scope of protection of the present invention. Based on the technical solutions of the present invention, various modifications or variations that can be made by those skilled in the art without creative effort are still within the scope of protection of the present invention.

Claims

1. An amide derivative or a pesticide-acceptable salt or solvate, characterized in that, The amide derivative is named 5-chloro-N-(2-fluoro-3-(2-iodo-4-(perfluoropropan-2-yl)-6-(trifluoromethyl)phenyl)carbamoyl)phenyl)thiophene-2-carboxamide, with the molecular formula C1. 22 H9ClF 11 IN2O2S has the following chemical structural formula:

2. A pharmaceutical composition, characterized in that, Includes an amide derivative or a pesticide-acceptable salt or solvate as described in claim 1.

3. The use of the amide derivative or pesticide-acceptable salt or solvate of claim 1 in the preparation of insecticides.

4. The application according to claim 3, characterized in that, The insecticide is used to control agricultural and forestry pests.

5. The application according to claim 3, characterized in that, The insecticide is used to control chewing mouthpart pests.

6. The use of the pharmaceutical composition of claim 2 in the preparation of an insecticide.

7. The application according to claim 6, characterized in that, The insecticide is used to control agricultural and forestry pests.

8. The application according to claim 6, characterized in that, The insecticide is used to control chewing mouthpart pests.

9. An insecticide, characterized in that, Its active ingredient is an amide derivative as described in claim 1 or a pesticide-acceptable salt or solvate.

10. An insecticide, characterized in that, The pharmaceutical composition comprising the claims 2.

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