A kind of amide derivative and application

Abstract

The invention discloses an amide derivative and its application. The amide derivative is 5-chloro-N-(2-fluoro-3-(2-iodo-4-(perfluoropropane-2-yl)-6-(trifluoromethyl)phenyl)carbamoyl)phenyl)thiophene-2-carboxamide. The amide derivative of the invention has excellent persistence and rapidity in killing and controlling agricultural and forestry pests, especially chewing mouthparts pests such as diamondback moth, beet armyworm, cotton bollworm, etc., and is not easy to produce cross-resistance with existing diamide compounds. Moreover, the safety to mammals is very excellent, and the safety to beneficial insects such as bees is excellent. The product has huge market potential in the field of agricultural and forestry pest control in the future and has very good prospects for promotion and application.

Description

Technical Field

[0001] The present invention relates to amide derivatives, in particular to an amide derivative and its application, belonging to the technical field of insecticide preparation. Background Art

[0002] Insecticides play an important role in pest control in my country's agriculture, forestry and public health. Organophosphorus, carbamate, pyrethroid, nicotinoid and macrolide insecticides were once widely used. However, with people's increasing attention to environmental protection and their own toxicity, pests' resistance or their ecotoxicity to the environment, these insecticides have been restricted or eliminated one after another. In recent years, diamide insecticides, led by flubendiamide, have been sold all over the world for their excellent insecticidal activity and lack of cross-resistance with traditional insecticides. However, with the passage of time, the resistance problem of diamide insecticides has become very prominent, and safety issues have gradually emerged. In recent years, domestic and foreign monitoring data show that they have medium and high levels of resistance to populations of the Chilo suppressalis, the rice leaf roller, the beet armyworm and the diamondback moth. Flubendiamide, chlorantraniliprole, cyanantraniliprole, tetrachlorantraniliprole, flubendiamide and other products have successively appeared safety issues such as serious harm to aquatic invertebrates, causing metamorphosis of silkworms, and affecting the flying ability of bees. The pesticide market is in urgent need of developing new high-efficiency, low-toxic and safe insecticides to control pests.

[0003] Bromifloc, a new type of diamide insecticide registered for the first time in the world in 2019, was successfully developed through structural optimization with flubendiamide as the forerunner. Its chemical structure is similar to that of chlorantraniliprole and flubendiamide, and its site of action overlaps with macrolide agents such as avermectin, but its mode of action is different from that of avermectin. It is still effective against pests resistant to macrolides and fipronil. Bromifloc is an allosteric modulator of GABA-gated chloride ion channels (also known as ionotropic GABA receptors). It mainly acts on a unique binding site on the ion channel, inhibiting the transfer of chloride ions into cells, causing insects to become overexcited or spasmodic, thereby showing rapid insecticidal activity. It is mainly used to control pests such as Lepidoptera, Coleoptera, Thysanoptera, termites, mosquitoes and flies on crops such as green leafy vegetables, perennial crops and cereals. Brofenac currently shows insecticidal activity far superior to traditional insecticides with its special structure and unique mechanism of action. As a new type of diamide insecticide, it has no cross-antagonism with existing insecticides and is safe to use. The sales volume of this product has gradually increased in recent years, and it is expected to replace the current "king" of insecticides, chlorfenac, in the future.

[0004] At present, in agricultural production, the application of pesticides is an important means of preventing and controlling plant diseases and insect pests. However, with the increase in the use and scope of existing pesticides, the increase in the use time, and the irregular use of some pesticides, some pests have gradually begun to develop a relatively large resistance to existing common pesticides, and the difficulty of pesticide control has become increasingly greater. The emergence of bromofenac resistance in the future is also inevitable. The current development and research of innovative pesticides is an effective way to deal with the resistance problem of pests. Therefore, the development of new high-efficiency, low-toxic and safe pesticides for pest control is of great significance in the agricultural field, and it is also a hot spot in the field of innovative pesticide research and development. Summary of the invention

[0005] The purpose of the present invention is to overcome the deficiencies of the prior art and to provide an amide derivative and its application.

[0006] To achieve the above object, the present invention adopts the following technical solutions:

[0007] 1. An amide derivative or a pesticide acceptable salt or solvate, wherein the name of the amide derivative is 5-chloro-N-(2-fluoro-3-(2-iodo-4-(perfluoropropane-2-yl)-6-(trifluoromethyl)phenyl)carbamoyl)phenyl)thiophene-2-carboxamide, the molecular formula is C 22 H 9 CIF 11 IN 2 O 2 S, chemical structure is as follows:

[0008]

[0009] 2. A pharmaceutical composition comprising the aforementioned amide derivative or its pesticide-acceptable salt or solvate.

[0010] 3. Use of the aforementioned amide derivative or its pesticide-acceptable salt or solvate in the preparation of insecticides.

[0011] As one of the preferred technical solutions, the insecticide is used to prevent and control agricultural and forestry pests.

[0012] As one of the preferred technical solutions, the insecticide is used to control chewing mouthpart pests.

[0013] As one of the further preferred technical solutions, 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.

[0014] As one of the further preferred technical solutions, the chewing mouthpart pests are selected from: diamondback moth, beet armyworm, Spodoptera litura, cabbage looper, and cotton bollworm.

[0015] 4. Use of the aforementioned pharmaceutical composition in the preparation of insecticides.

[0016] As one of the preferred technical solutions, the insecticide is used to prevent and control agricultural and forestry pests.

[0017] As one of the preferred technical solutions, the insecticide is used to control chewing mouthpart pests.

[0018] As one of the further preferred technical solutions, 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.

[0019] As one of the further preferred technical solutions, the chewing mouthpart pests are selected from: diamondback moth, beet armyworm, Spodoptera litura, cabbage looper, and cotton bollworm.

[0020] 5. An insecticide, the active ingredient of which is one of the aforementioned amide derivatives or its pesticide-acceptable salt or solvate.

[0021] 6. An insecticide comprising the aforementioned pharmaceutical composition.

[0022] Beneficial effects of the present invention:

[0023] The invention obtains a new compound CCXN-7-021 which can be used for preparing insecticides by screening, namely 5-chloro-N-(2-fluoro-3-(2-iodo-4-(perfluoropropane-2-yl)-6-(trifluoromethyl)phenyl)carbamoyl)phenyl)thiophene-2-carboxamide.

[0024] The applicant has confirmed through experiments that the novel amide derivative CCXN-7-021 of the present invention has excellent persistence and rapidity in killing and controlling agricultural and forestry pests, especially chewing mouthparts pests such as diamondback moth, beet armyworm, and cotton bollworm. According to the current indoor toxicity test results, the control effect of compound CCXN-7-021 on agricultural and forestry pests such as diamondback moth, beet armyworm, and cotton bollworm is better than that of the marketed product brofenac. The control effect of compound CCXN-7-021 on diamondback moth is 16 times that of brofenac. The control effect of compound CCXN-7-021 on beet armyworm is 10 times that of brofenac. The control effect of compound CCXN-7-021 on cotton bollworm is equivalent to that of brofenac. It is significantly better than the compound with similar structure (Comparative Example 1), the control effect of compound CCXN-7-021 on diamondback moth is 380 times that of comparative example 1, the control effect of compound CCXN-7-021 on beet armyworm is 150 times that of comparative example 1, and the control effect of compound CCXN-7-021 on cotton bollworm is about 10 times that of comparative example 1. Due to its special structure and mechanism of action, CCXN-7-021 is not likely to produce cross-resistance with traditional diamide compounds.

[0025] Moreover, CCXN-7-021 has excellent safety for mammals. Toxicology test data show that the acute oral toxicity LD50 >5000mg / kg, which is only slightly toxic according to the pesticide product toxicity classification standard, which is equivalent to the listed product brofenac. In addition, the environmental safety evaluation test results of CCXN-7-021 show that the toxicity to bees is at the poisoning level, while the listed product brofenac and similar structural compounds (Comparative Example 1) are highly toxic to bees. The safety of CCXN-7-021 to bees is better than that of the listed product brofenac and similar structural compounds (Comparative Example 1). At present, in order to protect the health of the ecosystem and control the potential adverse effects of high-risk pesticides on environmental organisms from the source, Europe and the United States have proposed a complete pesticide biosafety evaluation system for bees. my country has also listed the biological toxicity and safety evaluation of pesticides to bees as an important part of pesticide registration management and pesticide use environmental safety management. Under this background and trend, the future application scenarios of CCXN-7-021 will be far greater than brofenac.

[0026] In summary, CCXN-7-021 has huge market potential in the field of agricultural and forestry pest control in the future, and has very good promotion and application value and prospects. BRIEF DESCRIPTION OF THE DRAWINGS

[0027] Figure 1 is the hydrogen spectrum of the example compound. DETAILED DESCRIPTION

[0028] The present invention is further described below in conjunction with 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 contents.

[0029] Example 1 Compound CCXN-7-021

[0030] The chemical structure is as follows:

[0031]

[0032] The preparation method is as follows:

[0033]

[0034] Take 2-trifluoromethyl-4-(heptafluoroisopropyl)aniline (5g, 15.2mmol) and put it into a 50ml three-necked flask, add 15mL of anhydrous ethanol, and start stirring. Control the temperature in an ice-water bath, add 1.58g of 98% concentrated sulfuric acid, and exotherm is obvious. After addition, slowly cool down to below 20°C. Then add N-iodosuccinimide (3.76g, 16.7mmol), move to an oil bath, heat the oil bath to 40°C, heat and stir for about 3h, monitor by TLC, petroleum ether: ethyl acetate = 10:1 (volume ratio), and the raw material is basically reacted. Use 4M sodium hydroxide aqueous solution to adjust the pH to neutral, add 20ml of ethyl acetate to extract, stir and separate, extract 3 times, combine the organic phases, wash with saturated brine, dry over anhydrous sodium sulfate, and concentrate under reduced pressure to obtain (4-heptafluoroisopropyl-2-iodo-6-(trifluoromethyl)aniline) iodo intermediate 1, about 7g of oil, and the crude product is used for the next step.

[0035]

[0036] Add 2-fluoro-3-nitrobenzoic acid (3.5 g, 18.9 mmol) to a 50 mL three-necked flask, add 12 mL of toluene, add 0.05 mL of dimethylformamide, add thionyl chloride (2.8 g, 23.6 mmol) under stirring at room temperature, then heat to reflux and stir for 2 h, monitor the reaction by TLC (add methanol to the reaction solution and shake well, spot the plate with dichloromethane: methanol = 20:1 (volume ratio)), and the raw material reaction is complete. Concentrate under reduced pressure to remove the solvent and thionyl chloride, add 10 ml*2 of dichloromethane and dry it twice, then put it into a 50 mL three-necked flask, add 14 mL of 1,3-dimethyl-2-imidazolidinone, add (4-heptafluoroisopropyl-2-iodo-6-(trifluoromethyl)aniline) iodo intermediate 1 (7 g, crude product, 15.2 mmol) under stirring, and then stir overnight in an oil bath at 100 ° C. The reaction was detected by TLC (petroleum ether: ethyl acetate = 4:1, volume ratio). A small amount of both raw materials remained. The reaction was stopped, 16 mL of water was added to the reaction solution to quench, 20 mL of ethyl acetate was added, stirred, and the solution was separated by standing. The aqueous phase was extracted with 10 ml of ethyl acetate, and the organic phases were combined and washed with 50 ml of saturated brine twice. Drying over anhydrous sodium sulfate. The product was concentrated and purified by silica gel column (petroleum ether / ethyl acetate = 4:1) to obtain an off-white solid (2-fluoro-N-(2-iodo-4-(perfluoropropane-2-yl)-6-(trifluoromethyl)phenyl)-3-nitrobenzamide) iodo intermediate 2, 5.9 g, with a yield of 62%.

[0037]

[0038] Take (2-fluoro-N-(2-iodo-4-(perfluoropropane-2-yl)-6-(trifluoromethyl)phenyl)-3-nitrobenzamide) iodo intermediate 2 (5.9 g, 9.5 mmol) and put it into a 100 mL three-necked flask, add 36 mL of anhydrous ethanol, add anhydrous stannous chloride (7 g, 3.70 mmol) under stirring, then lower the temperature to 0°C, directly add 6.16 g of concentrated hydrochloric acid, add it completely, stir at 60°C for 2 h. TLC shows that the raw material reaction is complete. Add 4M sodium hydroxide to adjust the pH to 9-10, and a large amount of solid is precipitated. Filter directly and wash the solid with ethyl acetate. Collect the mother liquor, add 30 mL of ethyl acetate, add 10 mL of water, stir and separate, extract the aqueous phase with 10 mL of ethyl acetate, combine the organic phases, wash with 10 mL of saturated brine, dry over anhydrous sodium sulfate, and concentrate to obtain 3 g of brown solid. Use 10 ml of petroleum ether:ethyl acetate = 4:1 (volume ratio) to slurry for 2 hours to obtain a pure product, which is placed in a 45°C forced air oven to obtain 2.5 g of an off-white solid (3-amino-2-fluoro-N-(2-iodo-4-(perfluoropropane-2-yl)-6-(trifluoromethyl)phenyl)benzamide) iodinated common intermediate with a yield of 44.4%.

[0039]

[0040] 2-Chlorothiophene-5-carboxylic acid (1 g, 6.2 mmol) was added to 10 mL of dichloromethane, thionyl chloride (2 g, 16.8 mmol) and 0.15 ml of dimethylformamide, and the mixture was heated to 45 °C for 4 h. The mixture was sampled and shaken after adding methanol. TLC (petroleum ether:ethyl acetate=4:1, volume ratio) showed that the reaction of the raw materials was complete. The mixture was concentrated under reduced pressure at 45 °C to gradually precipitate solid. 5 mL of dichloromethane was added to dry the mixture to obtain a light yellow semisolid, which was dissolved in 3 ml of toluene for later use.

[0041] The (3-amino-2-fluoro-N-(2-iodo-4-(perfluoropropane-2-yl)-6-(trifluoromethyl)phenyl)benzamide) iodinated common intermediate (3 g, 5.1 mmol) was added to 10 mL of toluene, followed by the above-mentioned 2-chlorothiophene-5-carbonyl chloride, and 0.15 ml of dimethylformamide. The mixture was heated to 100 ° C. and reacted overnight. Sampling was performed, and ethyl acetate and water were added for shaking. TLC (petroleum ether: ethyl acetate = 1:1, volume ratio) showed that the reaction of the raw materials was complete, and the mixture was cooled to room temperature. Toluene was spin-dried at 50°C, and dichloromethane / methanol / water (volume ratio 20 / 1 / 10, 60 ml) was added and slurried for 3 h. The mixture was filtered and the filter cake was dried to obtain 1.5 g of off-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%.

[0042] The product hydrogen spectrum is shown in Figure 1 .

[0043] 1 H NMR (400 MHz, CDCl 3 )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 H 9 CIF 11 IN 2 O 2 S, [M+Na] + =758.8834

[0044] Comparative Example 1

[0045] Patent application CN114805294A (2891535-03-6)

[0046] The chemical structure is as follows:

[0047]

[0048] The preparation method is as follows:

[0049]

[0050] Add 130g of 2-trifluoromethyl-4-(heptafluoroisopropyl)aniline to a 500mL three-necked flask, add 200mL of DMF, add 86g of NBS in three batches over 30min, and then heat to 60°C and stir for 2h. TLC monitoring, PE:EA=10:1, the raw material reaction is complete. Pour the reaction solution into 2L of water, add 1L*2 of ethyl acetate to extract twice, combine the organic phases, and wash with 200mL of 10% sodium thiosulfate aqueous solution. After separation, add anhydrous sodium sulfate to the organic phase and dry it. Rotary evaporation, 130g of orange oily product (2-bromo-4-(perfluoropropane-2-yl)-6-(trifluoromethyl)aniline) brominated intermediate 1 is obtained, a small amount of solid is precipitated, the yield is 81%, no further purification is performed, and the next step is continued.

[0051]

[0052] Add 72g of 2-fluoro-3-nitrobenzoic acid, 100mL of toluene and 1mL of DMF (N,N-dimethylformamide) to a 500ml three-necked flask. Add 68g of thionyl chloride under stirring at room temperature, then heat to reflux and stir for 2h in an oil bath, monitor the reaction by TLC (shake the reaction solution with methanol, and spot the plate with DCM:methanol 10:1 (volume ratio)), and the reaction of 2-fluoro-3-nitrobenzoic acid is complete. Rotary evaporation at 50°C, remove toluene under reduced pressure. Add 200mL of DMI (1,3-dimethyl-2-imidazolidinone) to the obtained oil, add 130g of (2-bromo-4-(perfluoropropane-2-yl)-6-(trifluoromethyl)aniline) bromo intermediate 1, stir overnight in an oil bath at 100°C, and detect the completion of the reaction by TLC (PE:EA=4:1, volume ratio). The reaction solution was poured into 600 mL of water, extracted with EA 400 mL*3, and the organic phases were combined and dried over anhydrous sodium sulfate. The mixture was subjected to rotary evaporation under reduced pressure. A large amount of solid was precipitated during the rotary evaporation. When only a small amount of solvent was left, the solid was filtered to obtain an off-white product (N-(2-bromo-4-(perfluoropropane-2-yl)-6-(trifluoromethyl)phenyl)-2-fluoro-3-nitrobenzamide) bromo intermediate 2, 120 g, with a yield of 65.4%.

[0053]

[0054] In a 1L reaction bottle, add (N-(2-bromo-4-(perfluoropropane-2-yl)-6-(trifluoromethyl)phenyl)-2-fluoro-3-nitrobenzamide) bromo intermediate 2 100g, ethanol 300mL, hydrochloric acid 50mL, stir for 10min, add anhydrous stannous chloride 96g, and then heat to 60°C and stir for 2h. TLC monitoring, PE:EA=4:1 (volume ratio), after the raw materials react, ethanol is removed by rotary evaporation, and the pH is adjusted to 10 with a mass concentration of 10% sodium hydroxide aqueous solution. A large amount of off-white solid is precipitated, and EA 300mL*3 is added to extract the aqueous phase (with solid extraction), the upper organic phase is combined, anhydrous magnesium sulfate is added to dry, and then rotary evaporation is performed to obtain a yellow to brown oily product (3-amino-N-(2-bromo-4-(perfluoropropane-2-yl)-6-(trifluoromethyl)phenyl)-2-fluorobenzamide) bromo intermediate 3, 60g, with a yield of 63%. No further purification was performed and it was directly used for the next step.

[0055]

[0056] Under ice-water bath, 237g sulfuric acid was added to a 500mL three-necked flask, and 50g of (3-amino-N-(2-bromo-4-(perfluoropropane-2-yl)-6-(trifluoromethyl)phenyl)-2-fluorobenzamide) brominated intermediate 3 was added three times with stirring. After stirring for 10min, 41mL of 37% formaldehyde aqueous solution was added dropwise while maintaining the temperature of the reaction solution below 40°C. After the addition was completed, the mixture was stirred at 40°C for 2h. The petroleum ether (PE): ethyl acetate (EA) = 4:1 (volume ratio) was monitored by TLC, and no raw material remained. The reaction solution was poured into 300 mL of ice water and the pH was adjusted to 10 with 4 M sodium hydroxide aqueous solution. The aqueous phase was then extracted with 300 mL*3 of ethyl acetate, the organic phases were combined, anhydrous magnesium sulfate was added to the organic phases and dried for 1.5 h, filtered, the organic phase was spin-dried, mixed with the sample (70 g of 100-200 mesh silica gel) and purified on a column, passed through a column (250 g of 200-300 mesh silica gel) with polar PE:EA=20:1-10:1 (volume ratio), and 27 g of an off-white powder (N-(2-bromo-4-(perfluoropropane-2-yl)-6-(trifluoromethyl)phenyl)-2-fluoro-3-(methylamino)benzamide) was obtained with a yield of 53%.

[0057]

[0058] Take 0.8 g of 2-chlorothiophene-5-carboxylic acid, add 10 ml of dichloromethane (DCM), add 0.8 g of thionyl chloride, 0.15 ml of DMF, set the oil bath at 45°C, react for 4 hours, take a sample, add methanol and shake, TLC (PE:EA=4:1, volume ratio) shows that the raw material reaction is complete, concentrate at 45°C under reduced pressure, and solid gradually precipitates. Add 5 mL of DCM and dry it to obtain a light yellow semisolid, add 2 mL of toluene, and use it as reaction solution A.

[0059] Take 2g (3-amino-N-(2-bromo-4-(perfluoropropane-2-yl)-6-(trifluoromethyl)phenyl)-2-fluorobenzamide) brominated intermediate 3, add 10ml toluene and stir magnetically. The solid does not dissolve. Add it dropwise into reaction solution A, add 0.15ml N,N-dimethylformamide (DMF), heat to 100°C, react for 2h, take a sample, add EA and water to shake, TLC (PE:EA=1:1, volume ratio) shows that the raw material reaction is complete, and stop heating. When the temperature was lowered, a solid precipitated. The solid was filtered off, and 10 ml of DCM:MEOH = 20:1 (volume ratio) was added. The mixture was slurried for 0.5 h and filtered off to obtain an off-white powder. The mixture was washed with water (10 ml*3 times) and dried at 40°C overnight to obtain 1.2 g of off-white solid N-(3-((2-bromo-4-(perfluoropropane-2-yl)-6-(trifluoromethyl)phenyl)carbamoyl)-2-fluorophenyl)-5-chlorothiophene-2-carboxamide. The yield was 47% and the purity was 99.23%.

[0060] 1 H 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 H 9 BrClF 11 N 2 O 2 S, [M+H] + =690.9128

[0061] Comparative Example 2

[0062] Compound CCXN-7-002

[0063]

[0064] The preparation method is as follows:

[0065] The preparation method of the brominated common intermediate is the same as that of Comparative Example 1.

[0066]

[0067] 2 g of 2-chlorothiophene-5-carboxylic acid was added into 20 ml of DCM, 4 g of thionyl chloride and 0.15 ml of DMF, and the mixture was heated to 45 °C for 4 h. The mixture was sampled, and methanol was added and shaken. TLC (PE:EA=4:1, volume ratio) showed that the reaction of the raw material was complete. The mixture was concentrated under reduced pressure at 45 °C to gradually precipitate solid. 10 mL of DCM was added to dry the mixture to obtain a light yellow semisolid, which was dissolved in 5 mL of toluene for later use.

[0068] Add 5 g of (N-(2-bromo-4-(perfluoropropane-2-yl)-6-(trifluoromethyl)phenyl)-2-fluoro-3-(methylamino)benzamide) brominated common intermediate to 20 ml of toluene, then add the above-mentioned 2-chlorothiophene-5-carbonyl chloride, add 0.15 ml of DMF, heat to 100°C and react overnight, take a sample, add EA and water to shake, TLC (PE:EA=1:1) shows that the raw material has reacted, and cool to room temperature. Toluene was spin-dried at 50°C, DCM / methanol / water (volume ratio 20 / 1 / 10, 60 mL) was added and slurried for 3 h, filtered, and the filter cake was dried to obtain 2.5 g of off-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%.

[0069] 1 H NMR (400 MHz, CDCl 3 )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 N 2 O 2 S, [M+H] + =704.9286

[0070] Comparative Example 3

[0071] Compound CCXN-7-008

[0072]

[0073] The preparation method is as follows:

[0074] The preparation method of (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.

[0075]

[0076] Add 2g of 1-naphthoic acid, 10ml of toluene, and 0.15ml of DMF to a 50ml reaction tube, then drop 4.14g of thionyl chloride, heat to 100℃ and react for 4h, take a sample, add methanol to shake, and detect the complete reaction of 1-naphthoic acid by TLC (DCM:MEOH=10:1, volume ratio). Rotary evaporate at 45~55℃ to dry the solvent, then add 5mL of toluene to dissolve and set aside.

[0077] Take a 50ml reaction tube, add 3g (N-(2-bromo-4-(perfluoropropane-2-yl)-6-(trifluoromethyl)phenyl)-2-fluoro-3-(methylamino)benzamide) bromine common intermediate, 20mL toluene, add the above 1-naphthoyl chloride under stirring, a small amount of bubbles are generated, and the temperature is raised to 100°C for reaction for 3h. TLC detection (PE:EA=4:1, volume ratio) shows that the raw materials have basically reacted, the reaction is stopped, and the temperature is brought to room temperature. Toluene is spin-dried at 50°C, DCM / methanol / water (volume ratio 20 / 1 / 10, 60mL) is slurried for 3h, filtered, and the filter cake is dried to obtain an off-white solid N-(3-((2-bromo-4-(perfluoropropane-2-yl)-6-(trifluoromethyl)phenyl)carbamoyl)-2-fluorophenyl)-N-methyl-1-naphthamide 2.4g, yield: 64%, purity: 98.49%.

[0078] 1 H 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 F 11 N 2 O 2 , [M+H] + =715.0379.

[0079] Comparative Example 4

[0080] Compound CCXN-7-009

[0081]

[0082] The preparation method is as follows:

[0083] The preparation method of (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.

[0084]

[0085] In a 50 ml reaction tube, add 2 g of 2-naphthoic acid, 10 ml of toluene, and 0.15 ml of DMF. Add 4.14 g of thionyl chloride dropwise while stirring. Heat to 100 °C and react for 4 h. Take a sample and add methanol for shock. TLC (DCM:MEOH=10:1, volume ratio) is used to detect whether the reaction of 2-naphthoic acid is complete. After the solvent is dried at 45 °C, add 5 ml of toluene to dissolve it for later use.

[0086] Take a 50ml reaction tube, add 3g (N-(2-bromo-4-(perfluoropropane-2-yl)-6-(trifluoromethyl)phenyl)-2-fluoro-3-(methylamino)benzamide) bromo common intermediate, 20mL toluene, add the above 2-naphthoyl chloride dropwise under stirring, and heat to 100°C for 6h. TLC detection (PE:EA=4:1, volume ratio) shows that the raw materials have basically reacted, and the reaction is stopped. Toluene is spin-dried at 50°C, DCM / methanol / water (volume ratio 20 / 1 / 10, 60ml) is pulped for 3h, filtered, and the filter cake is dried to obtain 1.5g of off-white solid N-(3-((2-bromo-4-(perfluoropropane-2-yl)-6-(trifluoromethyl)phenyl)carbamoyl)-2-fluorophenyl)-N-methyl-2-naphthamide, yield: 40%, purity: 98.26%.

[0087] 1 H 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 F 11 N 2 O 2 , [M+H] + =715.0246

[0088] Comparative Example 5

[0089] Compound CCXN-7-010

[0090]

[0091] The preparation method is as follows:

[0092] The preparation method of (3-amino-2-fluoro-N-(2-iodo-4-(perfluoropropane-2-yl)-6-(trifluoromethyl)phenyl)benzamide) iodinated common intermediate is the same as that in Example 1.

[0093]

[0094] Add 2g of 1-naphthoic acid, 5ml of toluene, 0.15ml of DMF, and drop 4.14g of thionyl chloride into a 50ml reaction tube, heat to 100℃ and react for 3h, take a sample, add methanol to shake, and detect the complete reaction of 1-naphthoic acid by TLC (DCM:MEOH=10:1, volume ratio). Rotary evaporate at 45℃ and dry, then add 5ml of toluene to dissolve and set aside.

[0095] Take a 50ml reaction tube, add 5g (3-amino-2-fluoro-N-(2-iodo-4-(perfluoropropane-2-yl)-6-(trifluoromethyl)phenyl)benzamide) iodine common intermediate, 20ml toluene, add the above-mentioned 1-naphthoyl chloride, and heat to 100°C for 3h. TLC detection (PE:EA=4:1, volume ratio) shows that the raw materials are basically reacted, the reaction is stopped, toluene is spin-dried at 50°C, DCM / methanol / water (volume ratio 20 / 1 / 10, 60ml) is added and pulped for 3h, filtered, and the filter cake is dried to obtain 3g of off-white solid N-(2-fluoro-3-((2-iodo-4-(perfluoropropane-2-yl)-6-(trifluoromethyl)phenyl)carbamoyl)phenyl)-1-naphthamide, yield: 47%, purity: 97.81%.

[0096] 1 H 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 IN 2 O 2 , [M+H] + =746.9964

[0097] Comparative Example 6

[0098] Compound CCXN-7-011

[0099]

[0100] The preparation method is as follows:

[0101] The preparation method of (3-amino-2-fluoro-N-(2-iodo-4-(perfluoropropane-2-yl)-6-(trifluoromethyl)phenyl)benzamide) iodinated common intermediate is the same as that in Example 1.

[0102]

[0103] Add 2g of 2-naphthoic acid, 5ml of toluene, 0.15ml of DMF, and drop 4.14g of thionyl chloride into a 50ml reaction tube, heat to 100℃ and react for 3h, take a sample, add methanol to shake, and use TLC (DCM:MEOH=10:1, volume ratio) to detect that the 1-naphthoic acid has reacted completely. Rotary evaporate at 45℃ and dry, then add 5ml of toluene to dissolve and set aside.

[0104] Take a 50ml reaction tube, add 5g (3-amino-2-fluoro-N-(2-iodo-4-(perfluoropropane-2-yl)-6-(trifluoromethyl)phenyl)benzamide) iodine common intermediate, 20ml toluene, add the above 2-naphthoyl chloride, heat to 100°C and react for 3h. TLC detection (PE:EA=4:1, volume ratio) shows that the raw materials are basically reacted, stop the reaction, spin-dry toluene at 50°C, add DCM / methanol / water (volume ratio 20 / 1 / 10, 60ml) and beat for 3h, filter, and dry the filter cake to obtain 1.7g of off-white solid N-(2-fluoro-3-((2-iodo-4-(perfluoropropane-2-yl)-6-(trifluoromethyl)phenyl)carbamoyl)phenyl)-2-naphthamide, yield: 27%, purity: 99.52%.

[0105] 1 H 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,2H),8.04(d,J=7.5Hz,1H),7.97(s,1H),7.91(t,J=6.9Hz,1H),7.71–

[0106] 7.58(m,3H),7.44(t,J=7.8Hz,1H).C 28 H 14 F 11 IN 2 O 2 , [M+H] + =746.9996

[0107] Test example

[0108] The applicant conducted toxicological studies on the compounds obtained in the examples, and conducted control efficacy tests on the compounds obtained in the examples and comparative examples against agricultural and forestry pests.

[0109] 1. Toxicology studies

[0110] Rats were given a single oral administration of 500 mg / kg and 5000 mg / kg CCXN-7-021 suspension, and were observed for 2 consecutive days. No obvious abnormalities were found in the rats. After the observation, the surviving rats were autopsied, and no visible lesions were found in the main organs. 50 >5000mg / kg. According to the acute oral toxicity classification standard in the "Regulations on Pesticide Registration Information", the acute oral toxicity of CCXN-7-021 in rats is slightly toxic.

[0111] As shown in Table 1, the toxicological data of the compound CCXN-7-021 obtained in Example 1 is comparable to that of the marketed product bromofenac (purchased from Dezhou Hanhua Pharmaceutical Chemical Co., Ltd.), and both are slightly toxic according to the pesticide product toxicity classification standard.

[0112] Table 1. Comparison of toxicological data

[0113]

[0114] 2. Agricultural and forestry pest control effectiveness test

[0115] The indoor toxicity of the following compounds to Plutella xylostella, Spodoptera exigua and Helicoverpa armigera was evaluated by leaf dipping method in indoor tests. Reference criteria: Agricultural Industry Standard of the People's Republic of China "Guidelines for Indoor Bioassay Tests of Pesticides - Pesticides Part 14: Leaf Dipping Method" (NY / T 1154.14-2008).

[0116] As shown in Table 2, the compound CCXN-7-021 obtained in Example 1 has a better control effect on agricultural and forestry pests such as diamondback moth, beet armyworm, and cotton bollworm than the listed product brofenac, and its control effect on diamondback moth is 16 times that of brofenac, and its control effect on beet armyworm is 10 times that of brofenac, and its control effect on cotton bollworm is equivalent to brofenac. It is significantly better than Comparative Example 1, with a control effect on diamondback moth of 380 times that of Comparative Example 1, a control effect on beet armyworm of 150 times that of Comparative Example 1, and a control effect on cotton bollworm of about 10 times that of Comparative Example 1.

[0117] Table 2. Agricultural and forestry pest control effectiveness test

[0118]

[0119]

[0120] 3. Environmental safety evaluation test

[0121] Purpose of the experiment: To preliminarily characterize the oral toxicity of the following compounds to honey bees.

[0122] Experimental target: Italian worker bee (Apis mellifera).

[0123] Test reference method and target toxicity reference standard: GB / T 31270.10-2014 "Chemical pesticide environmental safety assessment test guidelines Part 10: Honey bee acute toxicity test". (Table 3)

[0124] Table 3. Classification of pesticide toxicity to bees

[0125] toxicity bee grade <![CDATA[LD 50 (48h) / (μg a.i. / bee)]]> Toxic <![CDATA[LD 50 ≤0.001]]> Highly toxic <![CDATA[0.001<LD 50 ≤2]]> Poisoning <![CDATA[2<LD 50 ≤11]]> Low toxicity <![CDATA[LD 50 >11]]>

[0126] As shown in Table 4, the environmental safety evaluation test results of the compound CCXN-7-021 obtained in Example 1 show that its toxicity to bees is moderate. The toxicity of bromofenac to bees is high. The toxicity of Comparative Example 1 to bees is high.

[0127] Table 4. Environmental safety evaluation test

[0128]

[0129] Although the above describes the specific implementation mode of the present invention in conjunction with the accompanying drawings, it is not intended to limit the scope of protection of the present invention. Based on the technical solution of the present invention, various modifications or variations that can be made by those skilled in the art without creative work are still within the scope of protection of the present invention.

Claims

1. An amide derivative or a pesticide-acceptable salt, characterized in that: The name of the amide derivative is 5-chloro-N-(2-fluoro-3-(2-iodo-4-(perfluoropropane-2-yl)-6-(trifluoromethyl)phenyl)carbamoyl)phenyl)thiophene-2-carboxamide, and the molecular formula is C 22 H9ClF 11 IN2O2S, the chemical structure is as follows: 。 2. A pharmaceutical composition, characterized in that It comprises an amide derivative or a pesticide-acceptable salt as claimed in claim 1.

3. Use of an amide derivative or a pesticide-acceptable salt according to claim 1 in the preparation of an insecticide for controlling lepidopteran pests.

4. Use of the pharmaceutical composition according to claim 2 in the preparation of an insecticide for controlling lepidopteran pests.

5. An insecticide, characterized in that: The active ingredient is an amide derivative or a pesticide-acceptable salt as claimed in claim 1.

6. An insecticide, characterized in that: A pharmaceutical composition comprising the pharmaceutical composition of claim 2.

Images