Pyrethroid compound containing benzyl fluorine structure as well as preparation method and application of pyrethroid compound

Abstract

The invention belongs to the technical field of chemical synthesis, and relates to a pyrethroid compound capable of being used for killing insects, in particular to a pyrethroid compound containing a benzyl fluorine structure, a preparation method of the pyrethroid compound and application of the pyrethroid compound to prevention and control of pests such as resistant mosquitoes and flies. The compound is a compound as shown in a general formula I, and isomers and salts thereof. The pyrethroid compound containing the benzyl fluorine group is novel in structure, and the activity of the pyrethroid compound containing the benzyl fluorine group to mosquitoes and flies is obviously improved compared with the activity of an analogue containing a perfluthrin intermediate 2, 3, 5, 6-tetrafluoro-4-methylbenzyl alcohol structure; the activity of part of compounds on resistant mosquitoes in Guangzhou areas is 2-3 times that of tetramefluthrin; the compound has a novel structure and an excellent control effect on target sanitary pests and resistant mosquitoes, so that the compound is suitable for development of novel mosquito-repellent incense products. I

Description

Technical Field

[0001] This invention belongs to the field of chemical synthesis technology and relates to a pyrethroid compound that can be used for insecticidal purposes. Specifically, it relates to a pyrethroid compound containing a benzyl fluoride structure, its preparation method, and its application in controlling resistant mosquitoes, flies, and other pests. Background Technology

[0002] Mosquitoes, flies, and other sanitary pests are vectors for many diseases, including dengue fever and chikungunya, threatening human health. Controlling sanitary pests helps control the spread of these infectious diseases. Pyrethroids are the most commonly used insecticides for mosquito and fly control. However, long-term and frequent use has led to serious resistance in mosquitoes. Resistance not only affects the effectiveness and lifespan of insecticides, but high-dose use also causes environmental pollution. Developing novel compounds with novel structures can address the resistance problem to some extent.

[0003] In pesticide development, introducing fluorine atoms can alter the permeability, stability, and lipophilicity of compounds. It can also change the binding ability of compounds to target enzymes and receptors, or hinder the metabolic inactivation of compounds by organisms, thereby improving the bioactivity of pesticides. Introducing fluorine atoms into the molecule is also a common strategy in the creation of pyrethroids; many pyrethroid molecules, whether in the acid or alcohol moiety, contain fluorine atoms, such as cypermethrin and chlorpyrifos. However, the specific location and number of fluorine atoms introduced need further consideration regarding their effectiveness in improving activity. Summary of the Invention

[0004] The technical problem to be solved by the present invention is to address the shortcomings of the existing technology by providing a pyrethroid compound containing a benzyl fluoride structure, its preparation method, and its application in controlling resistant mosquitoes, flies, and other pests.

[0005] To achieve the above objectives, the present invention adopts the following technical solution: A pyrethroid compound containing a benzyl fluoride structure, the compound being the compound shown in general formula I, its isomers, and its salt. Ⅰ In the formula, R1 and R2 may be the same or different and are selected from hydrogen, halogen, cyano, unsubstituted or substituted C1-C groups. 10 Alkyl or C3-C 10 The cycloalkyl group has the following substituents: halogen and cyano.

[0006] Preferably, the compound is a compound of general formula I, and its chiral configuration and cis-trans isomers of the double bond. In the formula, R1 is selected from hydrogen, halogen, methyl, cyano or trifluoromethyl, and R2 is selected from hydrogen, halogen or methyl.

[0007] The chiral configuration, that is, the preferred chiral configuration of the two chiral carbons on the three-membered ring is dextrorotatory trans, that is, the carbon at position 1 is in the R configuration, and the substituent at position 3 is on the other side of the three-membered ring. The preferred configuration of the double bond is the cis-trans isomer.

[0008] A method for preparing pyrethroid compounds containing a benzyl fluoride structure includes the following steps: (1) Synthesis of 2,3,5,6-tetrafluoro-4-fluoromethyl-benzyl alcohol: Intermediate 1 Intermediate 1 was synthesized from tetrafluoro-1,4-dibenzyl alcohol under the action of a halogenating agent or a substituted sulfonyl chloride. Then, intermediate 1 was reacted with KF in solvent I under the action of a phase transfer catalyst to generate 2,3,5,6-tetrafluoro-4-fluoromethyl-benzyl alcohol. In intermediate 1, R3 was selected from halogen, C1-C3 alkyl sulfonate group, C1-C3 haloalkyl sulfonate, unsubstituted or substituted phenyl sulfonate group, wherein the substituent is methyl or nitro.

[0009] (2) Acyl chloride reaction: The corresponding chrysanthemic acid acyl chloride is obtained by chlorinating the corresponding acyl chloride; (3) The acyl chloride obtained in step (2) and the benzyl alcohol obtained in step (1) are reacted under the action of a base to obtain the compound shown in general formula I.

[0010] In step (1), intermediate 1, phase transfer catalyst, and KF are added to solvent I, and the temperature is raised to 100℃-150℃ (preferably 100℃-120℃) to react and obtain 2,3,5,6-tetrafluoro-4-fluoromethyl-benzyl alcohol.

[0011] Solvent I is one or more of amide solvents, sulfones, or sulfoxide solvents; the phase transfer catalyst is a quaternary ammonium salt or a crown ether.

[0012] The amide solvent is formamide, N,N-dimethylformamide, N,N-dimethylacetamide, or N-methylpyrrolidone, and the sulfone or sulfoxide solvent is any one or more of sulfolane or dimethyl sulfoxide.

[0013] The amount of potassium fluoride used is 1-2 molar equivalents of the intermediate, preferably 1-1.2 molar equivalents. More KF can also react, but it will increase the cost of use.

[0014] The phase transfer catalyst includes quaternary ammonium salts such as tetrabutylammonium bromide and tetramethylammonium chloride, and crown ethers such as 18-crown-6. The amount of phase transfer catalyst used is 0.001-0.1 molar equivalents of KF, preferably 0.001-0.005. More catalyst can be used, but this will increase the cost of use and will not provide any additional benefit.

[0015] In step (2), the acyl chloride reaction is specifically operated as follows: chrysanthemic acid is dissolved in solvent II and heated to the normal pressure reflux temperature (39-140℃) of the reaction solvent. Dichlorosulfoxide is added dropwise under reflux. After the addition is completed, the mixture is kept at 10-60℃ for 0.5-2 hours. After the raw material is completely converted in the gas phase, the solvent is removed to obtain chrysanthemic acid acyl chloride.

[0016] The solvent is any one, two or more of n-hexane, cyclohexane, methylcyclohexane, benzene, toluene, xylene, etc., mixed in any proportion, preferably n-hexane; the amount of solvent II is 3 to 10 times that of chrysanthemic acid.

[0017] The thionyl chloride used is in an amount of 1-3 molar equivalents of chrysanthemic acid, preferably 1.2 molar equivalents. In step (3), 2,3,5,6-tetrafluoro-4-fluoromethyl-benzyl alcohol is dissolved in toluene and then an acid-binding agent is added. The acyl chloride obtained in step (2) is added dropwise at 0-30°C, and then the reaction is carried out to obtain the pyrethroid compound containing the benzyl fluoride structure described in Formula I. The molar ratio between 2,3,5,6-tetrafluoro-4-fluoromethyl-benzyl alcohol, the acid-binding agent and the acyl chloride is 0.9-1.2:1.0-1.3:1.

[0018] The specific procedure is as follows: 2,3,5,6-tetrafluoro-4-fluoromethyl-benzyl alcohol is dissolved in toluene, and then an acid-binding agent is added. Chrysanthemic yl chloride is added dropwise at 0-10℃. After the addition is complete, the mixture is kept at 0-10℃ for 0.5-2 hours. After complete conversion of benzyl alcohol in the gas phase, the pH of the system is neutralized to 6-7 with dilute hydrochloric acid, and the layers are separated. The organic phase is then separated by solvent removal, column chromatography, and solvent removal to obtain pyrethroid compounds containing benzyl fluoride structures.

[0019] The acid-binding agent is triethylamine, pyridine, or liquid alkali (sodium hydroxide aqueous solution).

[0020] The amount of toluene used is 3 to 10 times the weight of chrysanthyl chloride.

[0021] The application of the pyrethroid compound containing the benzyl fluoride structure described above, specifically the application of the pyrethroid compound containing the benzyl fluoride structure described in Formula I as an insecticide for the control of sanitary pests.

[0022] The compound of Formula I is used to make mosquito coils or aerosols for the control of resistant mosquitoes and flies.

[0023] In the above technical solution, when the pyrethroid compound containing benzyl fluoride structure is used as an insecticide to control sanitary pests, the compound represented by Formula I is made into an aerosol (content 0.3%) or mosquito coil (content 0.1%) for killing mosquitoes, flies, etc.

[0024] Compared with existing technologies, this invention provides a novel pyrethroid compound containing a benzyl fluoride group, which exhibits significantly enhanced activity against mosquitoes and flies compared to analogs containing the 2,3,5,6-tetrafluoro-4-methylbenzyl alcohol structure of the pyrethroid intermediate. Some compounds show 2-3 times the activity of tetrafluoromethrin against resistant mosquitoes in the Guangzhou area. The novel structure and excellent efficacy against target pests and resistant mosquitoes make this type of compound suitable for the development of new mosquito coil products. Detailed Implementation

[0025] The following describes in detail the specific embodiments of the technical solution of the present invention, but the present invention is not limited to the following: The main raw materials used in the embodiments of this invention, namely tetrafluoro-1,4-dibenzyl alcohol, 2,2-dimethyl-3-(2-methyl-1-propenyl)cyclopropanecarboxylic acid (hereinafter referred to as DE chrysanthemic acid), 3-(2,2-dichlorovinyl)-2,2,-dimethylcyclopropanecarboxylic acid (hereinafter referred to as DV chrysanthemic acid), (Z)-2,2-dimethyl-3-(2-methyl-1-propenyl)cyclopropanecarboxylic acid (hereinafter referred to as meta-acid), cypermethrin, 2,3,5,6-tetrafluoro-4-methyl-benzyl alcohol used to synthesize the control compound, and the control sample tetrafluoromethoxyphen ... Other chrysanthemic acids, such as (Z)-3-(2-cyanovinyl)-2,2-dimethylcyclopropanecarboxylic acid (hereinafter referred to as monocyanic acid), can be synthesized according to patent CN202310032950.1; (Z)-3-(2-cyanopropenyl)-2,2-dimethylcyclopropanecarboxylic acid (hereinafter referred to as Momfluorothrin acid) can be synthesized according to EP2508509; and (Z)-2,2-dimethyl-3-(2-trifluoromethylvinyl)cyclopropanecarboxylic acid can be synthesized according to US2012 / 76846.

[0026] The present invention will now be described in conjunction with specific embodiments: Example 1: (1) Synthesis of 2,3,5,6-tetrafluoro-4-fluoromethyl-benzyl alcohol In a 250 mL four-necked flask equipped with a stirrer, 21 g (100 mmol) of tetrafluoro-1,4-dibenzyl alcohol was dissolved in 80 g of toluene, and 16 g (150 mmol) of sodium carbonate was added. Then, 10.3 g (90 mmol) of methanesulfonyl chloride was added dropwise at 0–5 °C, and the mixture was kept at room temperature for 2 h. 30 g of water was added and stirred. The mixture was separated, and the oil layer was purified by hexane:ethyl acetate = 5:1 (w / w) column chromatography to give 21.2 g of a pale yellow solid, 2,3,5,6-tetrafluoro-4-hydroxymethyl-benzyl methanesulfonate, in 82% yield, calculated as methanesulfonyl chloride.

[0027] In a 250 mL four-necked flask equipped with a stirrer, 21.2 g (74 mmol) of 2,3,5,6-tetrafluoro-4-hydroxymethyl-benzyl methanesulfonate, 71 mg (0.22 mmol) of tetrabutylammonium bromide, 6.4 g (111 mmol) of dry KF, and 80 g of N,N-dimethylacetamide were added to the reaction flask. The temperature was raised to 120-125 °C and maintained for 5 h. The conversion of 2,3,5,6-tetrafluoro-4-hydroxymethyl-benzyl methanesulfonate was monitored by gas chromatography. After the sulfonate conversion was complete, the mixture was cooled to room temperature, filtered, and the filtrate was desolventized. The solution was then purified by column chromatography using n-hexane:ethyl acetate = 5:1 (w / w) to obtain 10.5 g of colorless crystalline solid 2,3,5,6-tetrafluoro-4-fluoromethyl-benzyl alcohol, with a yield of 67%.

[0028] (2)(1) R ,3 R Synthesis of 2,2-dimethyl-3-(2-methylpropenyl)cyclopropionyl chloride In a 250 mL four-necked flask equipped with a stirrer, 16.8 g (100 mmol) of DE chrysanthemic acid was dissolved in 70 g of toluene. The temperature was raised to 55-60 °C, and 14.3 g (120 mmol) of thionyl chloride was added dropwise. The mixture was kept at this temperature for 2 hours after the addition was complete. Gas chromatography showed that the DE chrysanthemic acid conversion was complete, and the solvent was removed to obtain 17.9 g of a colorless oily liquid (1... R ,3 R 2,2-Dimethyl-3-(2-methylpropenyl)cyclopropionyl chloride (hereinafter referred to as DE chrysanthyl chloride), yield 96%.

[0029] (3) 2,3,5,6-Tetrafluoro-4-(fluoromethyl)benzyl (1 R ,3 R Synthesis of 2,2-dimethyl-3-(2-methylpropenyl)cyclopropane carboxylate (compound 1) In a 250 mL four-necked flask equipped with a stirrer, 10.5 g (49.5 mmol) of 2,3,5,6-tetrafluoro-4-fluoromethyl-benzyl alcohol was dissolved in 40 g of toluene, followed by the addition of 26.4 g of 15% sodium hydroxide aqueous solution and 18 mg (0.15 mmol) of 4-N,N-dimethylamino-pyridine. The mixture was cooled to 0-5 °C, and 10.1 g (54.5 mmol) of DE chrysanthyl chloride was added dropwise. After the addition was complete, the mixture was kept at this temperature for 0.5 h. Gas chromatography was used to confirm the complete conversion of 2,3,5,6-tetrafluoro-4-fluoromethyl-benzyl alcohol. The mixture was separated, and after solvent removal from the oil layer, it was subjected to column chromatography with n-hexane:ethyl acetate = 10:1 (w / w) to obtain 16.5 g of colorless oily liquid 2,3,5,6-tetrafluoro-4-(fluoromethyl)benzyl (1 R ,3 R 2,2-Dimethyl-3-(2-methylpropenyl)cyclopropane carboxylate (compound 1), yield 92%.

[0030] Example 2: (1) Synthesis of 2,3,5,6-tetrafluoro-4-fluoromethyl-benzyl alcohol In a 250 mL four-necked flask equipped with a stirrer, 21 g (100 mmol) of tetrafluoro-1,4-dibenzyl alcohol was dissolved in 80 g of toluene, and 15 g (90 mmol) of 48% HBr was added. The mixture was heated to 60-65 °C and kept at this temperature for 4 h. The mixture was separated, and the oil layer was purified by column chromatography using n-hexane:ethyl acetate = 5:1 (w / w) to give 19.1 g of colorless crystalline solid 2,3,5,6-tetrafluoro-4-bromomethylbenzyl alcohol, in 78% yield, calculated as hydrogen bromide.

[0031] In a 250 mL four-necked flask equipped with a stirrer, 19 g (70 mmol) of 2,3,5,6-tetrafluoro-4-bromomethylbenzyl alcohol, 55 mg (0.21 mmol) of 18-crown-6, 8.2 g (140 mmol) of dried KF, and 80 g of N,N-dimethylformamide were added to the reaction flask. The temperature was raised to 120-125 °C and maintained for 3 h. The conversion of 2,3,5,6-tetrafluoro-4-bromomethylbenzyl alcohol was monitored by gas chromatography. After the conversion of benzyl bromide was complete, the mixture was cooled to room temperature, filtered, and the filtrate was desolventized. The solution was then purified by column chromatography using n-hexane:ethyl acetate = 5:1 (w / w) to obtain 10.8 g of colorless crystalline solid 2,3,5,6-tetrafluoro-4-fluoromethylbenzyl alcohol, with a yield of 73%.

[0032] (2)(1) R ,3 S Synthesis of 3-(2,2-dichlorovinyl)-2,2,-dimethylcyclopropionyl chloride In a 250 mL four-necked flask equipped with a stirrer, 20.8 g (100 mmol) of DE chrysanthemic acid was dissolved in 80 g of cyclohexane. The temperature was raised to 55-60 °C, and 14.3 g (120 mmol) of thionyl chloride was added dropwise. The mixture was kept at this temperature for 2 h after the addition was complete. Gas chromatography showed that the DV chrysanthemic acid conversion was complete, and the solvent was removed to obtain 22.1 g of a pale yellow oily liquid (1 R ,3 S 3-(2,2-dichlorovinyl)-2,2,-dimethylcyclopropionyl chloride (hereinafter referred to as DV chrysanthyl chloride), yield 98%.

[0033] (3) 2,3,5,6-Tetrafluoro-4-(fluoromethyl)benzyl (1 R ,3 S Synthesis of 3-(2,2-dichlorovinyl)-2,2-dimethylcyclopropane carboxylate (compound 2) In a 250 mL four-necked flask equipped with a stirrer, 10.5 g (49.5 mmol) of 2,3,5,6-tetrafluoro-4-fluoromethyl-benzyl alcohol was dissolved in 40 g of toluene, and 7.9 g (74.3 mmol) of sodium carbonate and 18 mg (0.15 mmol) of 4-N,N-dimethylamino-pyridine were added. Stirring was started, and the temperature was lowered to 0-5 °C. 12.3 g (54.5 mmol) of DV chrysyl chloride was added dropwise. After the addition was complete, the mixture was kept at this temperature for 1 h. Gas chromatography was used to confirm the complete conversion of 2,3,5,6-tetrafluoro-4-fluoromethyl-benzyl alcohol. The mixture was separated, and after solvent removal from the oil layer, it was purified by column chromatography with n-hexane:ethyl acetate = 10:1 (w / w) to obtain 18.9 g of a pale yellow oily liquid, 2,3,5,6-tetrafluoro-4-(fluoromethyl)benzyl (1... R ,3 S 3-(2,2-dichlorovinyl)-2,2-dimethylcyclopropane carboxylate (compound 2), 95% yield.

[0034] The pyrethroid compound containing the benzyl fluoride structure of the present invention was prepared according to the synthesis method of Examples 1-2, and its structural formula is shown in I: Formula I; R1 can be hydrogen, halogen, methyl, cyano, trifluoromethyl, etc., and R2 can be halogen, methyl, hydrogen, etc.

[0035] Table 1: List of some compounds 1-7 of the present invention and control compounds

[0036] The NMR and mass spectrometry characterization of the compounds of the present invention are as follows: Compound 1: 1 H-NMR (600 MHz, CDCl3) δ 5.52 (d, JH,F = 47.3 Hz, 2H), 5.26 (d, J = 12.2 Hz, 1H), 5.22 (d, J = 12.2 Hz, 1H), 4.88 (d, J = 7.7 Hz, 1H), 2.09 (dd, J 1= J 2= 6.5 Hz, 1H), 1.71(s, 3H), 1.69 (s, 3H), 1.39 (d, J = 5.3 Hz, 1H), 1.27 (s,3H), 1.13 (s, 3H). 13 C-NMR (600 MHz, CDCl3) δ 171.76, 146.11 ~ 145.81 (m, 2C),144.42 ~ 144.15 (m, 2C), 135.91, 120.74, 116.71 (td, J C,F = 67.4, 13.5 Hz),114.62 (dd, J C,F = 135.8, 68.2 Hz), 71.30 (d, J C,F = 676.7 Hz), 53.34, 34.29,33.30, 29.26, 25.51, 22.04, 20.34, 18.41. EI-MS (70 eV) m / z (%): 362 (5.29),195 (17.92), 145 (12.46), 123 (100), 81 (40.69), 43 (31.28). Compound 2: 1 H-NMR (600 MHz, CDCl3) δ 5.60 (d, J = 8.3 Hz, 1H), 5.52 (d, J H,F =47.3 Hz, 2H), 5.27 (d, J = 13.5 Hz, 1H), 5.27 (d, J = 13.7 Hz, 1H), 2.26 (dd, J 1=8.3 Hz, J 2= 5.4 Hz, 1H), 1.61 (d, J= 5.3 Hz, 1H), 1.29 (s, 3H), 1.19 (s, 3H). 13 C-NMR (600 MHz, CDCl3) δ 170.39, 146.05 ~ 145.82 (m, 2C), 144.40 ~ 144.15(m, 2C), 126.61, 122.44, 116.33 (td, J C,F = 67.2, 15.2 Hz), 114.83 (dd, J C,F =136.1, 68.2 Hz), 71.32 (d, J C,F = 676.2 Hz), 53.69, 34.27, 33.27, 29.45, 22.46,19.98. EI-MS (70 eV) m / z (%): 402 (0.64), 367 (19.27), 195 (98.58), 163 (100),145 (49.8), 127 (46.45), 91 (65.89), 77 (12.49). Compound 3: 1 H-NMR (600 MHz, CDCl3) δ 5.63 ~ 5.57 (m, 1H), 5.52 (d, J H,F =47.3 Hz, 2H), 5.27 (d, J = 12.2 Hz, 1H), 5.11 (td, J 1= 9.5 Hz, J 2= 1.1 Hz, 1H),5.13 ~ 5.09 (m, 1H), 2.18 (dd, J 1= 8.4 Hz, J 2= 5.5 Hz, 1H), 1.70 (dd, J 1= 7.0 Hz, J 2= 1.8 Hz, 3H), 1.46 (d, J = 5.3 Hz, 1H), 1.28 (s, 3H), 1.15 (s, 3H). 1313C-NMR (600 MHz, CDCl3) δ 171.57, 146.11 ~ 145.83 (m, 2C), 144.44 ~ 144.16 (m, 2C), 127.46, 126.71, 116.64 (td, J C,F J = 67.7, 14.4 Hz), 114.66 (dd, J C,F J = 135.5, 67.9Hz), 71.31 (d, J C,F J = 677.0 Hz), 53.41, 34.43, 32.15, 29.27, 21.99, 20.32, 13.39. EI-MS (70 eV) m / z (%): 348 (1.67), 195 (9.98), 153 (8.89), 145 (13.92), 109 (100), 81 (10.11), 67 (38.3), 55 (12.18), 43 (28.2). Compound 4: 1 1H-NMR (600 MHz, CDCl3) δ 6.88 (d, J J = 9.3 Hz, 1H), 5.52 (d, J H,F J = 47.3Hz, 2H), 5.28 (d, J J = 12.1 Hz, 1H), 5.22 (d, J J = 12.2 Hz, 1H), 2.20 (dd, J J1 = J J2 = 8.8 Hz, 1H), 1.99 (d, J J = 8.3 Hz, 1H), 1.30 (s, 6H). 13 13C-NMR (600 MHz, CDCl3) δ 169.46, 146.10 ~ 145.83 (m, 2C), 144.42 ~ 144.18 (m, 2C), 129.63 (q, J C,F J = 17.4Hz), 122.13 (q, J C,F J = 149.4 Hz), 120.37 (q, J C,F= 1078.1 Hz), 116.13 (td, J C,F =67.0, 13.9 Hz), 114.90 (dd, J C,F = 135.9, 68.1 Hz), 71.29 (d, J C,F = 676.6 Hz),53.56, 32.47, 31.11, 29.01, 28.21, 14.83.EI-MS (70 eV) m / z (%): 436 (0.03), 401(3.94), 225 (5.27), 195 (100), 161 (18.27), 145 (36.74), 141 (26.81), 125(5.1), 91 (6.14). Compound 5: 1 1H-NMR (600 MHz, CDCl3) δ 5.73 ~ 5.63 (m, 2H), 5.52 (d, J H,F =47.2Hz, 1H), 5.27 (s, 2H), 2.46 ~ 2.43 (m, 1H), 1.69(d, J = 5.3 Hz, 1H), 1.29(s, 3H), 1.20 (s, 3H). 13 13C-NMR (600 MHz, CDCl3) δ 170.11, 146.10 ~ 145.86 (m,2C), 144.40 ~ 144.14 (m, 2C), 138.95 (q, J C,F = 20.9 Hz), 123.14 (q, J C,F = 1083.7Hz), 120.31 (q, J C,F = 135.1 Hz), 116.32 (td, J C,F = 67.5, 14.2 Hz), 114.82 (dd, J C,F = 135.6, 68.4 Hz), 71.29 (d, J C,F= 677.0 Hz), 53.67, 35.65, 31.58, 30.22,21.97, 20.05. EI-MS (70 eV) m / z (%): 402 (0.52), 357 (0.63), 195 (95.61), 163(100), 145 (34.3), 123 (11.91), 99 (7.69), 79 (14.77), 41 (13.58). Compound 6: 1 H-NMR (600 MHz, CDCl3) δ 6.13 (dd, J 1= J 2 = 10.5 Hz, 1H), 5.53 (d, J H,F =47.3 Hz, 2H), 5.40 (d, J = 11.1 Hz, 1H), 5.28 (s, 2H), 2.56 (dd, J 1 = 10.4Hz J 2 = 5.3 Hz, 1H), 1.86 (d, J = 5.3 Hz, 1H), 1.35 (s, 3H), 1.24 (s, 3H). 13 C-NMR(600 MHz, CDCl3) δ 169.51, 151.49, 146.07 ~ 145.82 (m, 2C), 144.41 ~ 144.14(m, 2C), 116.15 (td, J C,F = 67.4, 14.5 Hz), 116.02, 114.90 (dd, J C,F = 135.9,67.8Hz), 100.30, 71.34 (d, J C,F = 676.3 Hz), 53.85, 35.93, 34.98, 31.07, 22.26,20.22.EI-MS (70 eV) m / z (%): 359 (0.38), 314 (1.83), 280 (1.54), 195 (82.43), 176 (11.45), 145 (39.96), 120 (100), 93 (61.14), 77 (23.46). Compound 7: 1H-NMR (600 MHz, CDCl3) δ 5.80 (d, J = 9.7 Hz, 1H), 5.53 (d, J H,F =47.3 Hz, 2H), 5.26 (s, 2H), 2.46 (dd, J 1 = 9.7 Hz J 2= ​​5.2 Hz, 1H), 1.96 (s, 3H), 1.72 (d, J = 5.2 Hz, 1H), 1.32 (s, 3H), 1.21 (s, 3H). 13 C-NMR (600 MHz, CDCl3) δ169.87, 146.06 ~ 145.88 (m, 2C), 144.70, 144.45 ~ 144.19 (m, 2C), 118.07,116.25 (td, J C,F = 68.4, 14.4 Hz), 114.84 (dd, J C,F = 135.5, 68.3 Hz), 110.83,71.34 (d, J C,F = 675.4 Hz), 53.78, 35.36, 34.67, 30.41, 22.36, 20.31, 20.28.EI-MS (70 eV) m / z (%): 373 (0.45), 328 (1.07), 195 (65.02), 176 (6.95), 160 (10.42), 145 (34.57), 134 (100), 107 (55.06), 91 (22.39), 79 (14.05). The following test examples demonstrate that the pyrethroid compounds synthesized in this invention are effective as pest control agents for sanitary pests.

[0037] Test Example 1: Compound Mosquito Repellent Activity Test Add 120 parts by weight of water to a mixture of 99.96 parts by weight of corn starch, charcoal powder and wood flour (1:5:4) and knead to form a shape. Then dry to form a mosquito coil base material (12.0 cm in diameter, 4 mm thick, 40 g per pair).

[0038] A 1 w / v solution of compound 1 in kerosene was prepared. 4 mL of the solution was uniformly sprayed onto the substrate using a microsyringe, and then left to dry at room temperature for 3 hours to obtain a 0.1 w / w% mosquito coil W1 containing compound 1.

[0039] Similarly, compounds 2-5 of the present invention in Table 1 and control compound 8 were prepared to obtain the corresponding mosquito coils.

[0040] The mosquito repellent efficacy of mosquito coils W1-W7 and the control compound was compared according to GB / T13917.4-2009. The test insects were Culex pipiens pallens, female mosquitoes that had not yet fed for 2-3 days after emergence. The procedure involved using a mosquito suction tube to collect 20 test mosquitoes, placing them in a sealed cylindrical testing device, randomly selecting a section of the tested mosquito coil, placing it on the coil holder, lighting it, and timing the process. After 1 minute, the mosquito coil was removed, and the number of mosquitoes knocked down was recorded at regular intervals. The experimental results are shown in Table 2. The results indicate that the mosquito repellent efficacy of the partially insecticidal compounds containing the benzyl fluoride structure of this invention is significantly better than that of the control compound tetrafluoroethylene.

[0041] Table 2: Comparison of mosquito-killing effects of some compounds of the present invention at 0.1% concentration with control compounds

[0042] Test Example 2: Adult Mosquito Contact Method for Testing Compound Activity Against Mosquitoes The resistance of the more active compounds 2, 4, and 5 from Test Example 1 to mosquitoes in the Guangzhou area was tested using the adult mosquito contact method according to GB / T26347-2010, along with the control agent tetrafluoromethrin.

[0043] The test compound was diluted to a series of concentrations using a mixture of white oil and ether in a 1:2 ratio, either proportionally or differentially. Preliminary experiments were conducted to determine the concentration range of the agent. At the lowest concentration, the larval mortality rate was less than 20%, and at the highest concentration, it was greater than 80%. 2 mL of each concentration was then evenly applied to... On a 1mm thick filter paper, after the solvent has evaporated for about 5 hours, it is placed inside the cylinder as a contact tube. Thirty non-blood-sucking female mosquitoes captured in Guangzhou city are then placed inside the contact tube using a mosquito suction tube. The partition is closed, and the process begins. The contact time was calculated. After 1 hour of contact, the partition was removed, and mosquitoes were blown into the recovery tube. The number of dead insects was recorded after 24 hours. The LC50 value was calculated using a regression curve based on the mortality rate corresponding to each concentration. The comparative results show that mosquitoes in Guangzhou exhibit significant resistance to tetrafluoroethylene permethrin, but no significant resistance to compounds 2, 4, and 5 in this invention. The results are shown in Table 3. Table 3: Activity tests of compounds and tetrafluoromethrin against adult mosquitoes in Guangzhou area

[0044] Test Example 3: Activity Test of Compound Aerosol An insecticide was prepared by heating and mixing 0.3 parts by weight of compound 1 and 59.7 parts by weight of kerosene until homogeneous. The resulting formulation was placed in an aerosol can equipped with a valve, through which 40.0 parts by weight of propane and butane were injected under pressure to obtain an insecticidal aerosol containing 0.3% compound 1.

[0045] The insecticidal aerosol was tested for efficacy against mosquitoes and flies according to GB / T13917.2-2009, using a sealed cylindrical apparatus. The specific procedure was as follows: the test insects were placed in the container, and after the insects resumed normal activity, 1g of the insecticide was sprayed quantitatively from the aerosol can. One minute later, the baffle was removed to allow the test insects to come into contact with the insecticide, and the time was immediately started and recorded. The number of test insects knocked down was recorded at regular intervals. After 20 minutes, all test insects were transferred to a clean insect rearing cage, and the number of dead insects was checked after 24 hours.

[0046] Table 4: Comparison of mosquito-killing effects of some compounds from this invention aerosol at 0.3% concentration with control compounds

[0047] Table 5: Comparison of fly-killing effects of some compounds from this invention in aerosol form at 0.3% concentration with control compounds.

[0048] The results showed that the aerosol prepared from the compounds with the benzyl fluoride structure of this invention had good control effects on mosquitoes and flies, and its effect was significantly better than that of the control compound. Several compounds showed activity exceeding that of tetrafluoromethrin.

[0049] The above examples are merely illustrative of the technical concept and features of the present invention and should not be construed as limiting the scope of protection of the present invention. All equivalent transformations or modifications made in accordance with the essence of the present invention should be included within the scope of protection of the present invention.

Claims

1. A pyrethroid compound containing a benzyl fluoride structure, characterized in that, The compounds are those represented by general formula I, their isomers, and their salts. Ⅰ In the formula, R1 and R2 may be the same or different and are selected from hydrogen, halogen, cyano, unsubstituted or substituted C1-C groups. 10 Alkyl or C3-C 10 The cycloalkyl group has the following substituents: halogen and cyano.

2. The pyrethroid compound containing a benzyl fluoride structure according to claim 1, characterized in that, The compound is the compound represented by general formula I, and its chiral configuration and cis-trans isomers of the double bond. In the formula, R1 is selected from hydrogen, halogen, methyl, cyano or trifluoromethyl, and R2 is selected from hydrogen, halogen or methyl.

3. The pyrethroid compound containing a benzyl fluoride structure according to claim 2, characterized in that, The chiral configuration, that is, the preferred chiral configuration of the two chiral carbons on the three-membered ring is dextrorotatory trans, that is, the carbon at position 1 is in the R configuration, and the substituent at position 3 is on the other side of the three-membered ring. The preferred configuration of the double bond is the cis-trans isomer.

4. The method for preparing the pyrethroid compound containing a benzyl fluoride structure according to claim 1, characterized in that, Includes the following steps: (1) Synthesis of 2,3,5,6-tetrafluoro-4-fluoromethyl-benzyl alcohol: Intermediate 1 Intermediate 1 was synthesized from tetrafluoro-1,4-dibenzyl alcohol under the action of a halogenating agent or a substituted sulfonyl chloride. Then, intermediate 1 was reacted with KF in solvent I under the action of a phase transfer catalyst to generate 2,3,5,6-tetrafluoro-4-fluoromethyl-benzyl alcohol. In intermediate 1, R3 was selected from halogen, C1-C3 alkyl sulfonate group, C1-C3 haloalkyl sulfonate, unsubstituted or substituted phenyl sulfonate, wherein the substituent is methyl or nitro. (2) Acyl chloride reaction: The corresponding chrysanthemic acid acyl chloride is obtained by chlorinating the corresponding acyl chloride; (3) The acyl chloride obtained in step (2) and the benzyl alcohol obtained in step (1) are reacted under the action of a base to obtain the compound shown in general formula I.

5. The method for preparing the pyrethroid compound containing a benzyl fluoride structure according to claim 4, characterized in that, In step (1), intermediate 1, phase transfer catalyst, and KF are added to solvent I, and the temperature is raised to 100℃-150℃ to react and obtain 2,3,5,6-tetrafluoro-4-fluoromethyl-benzyl alcohol.

6. The method for preparing the pyrethroid compound containing a benzyl fluoride structure according to claim 5, characterized in that, Solvent I is one or more of amide solvents, sulfones, or sulfoxide solvents; the phase transfer catalyst is a quaternary ammonium salt or a crown ether.

7. The method for preparing the pyrethroid compound containing a benzyl fluoride structure according to claim 6, characterized in that, The amide solvent is formamide, N,N-dimethylformamide, N,N-dimethylacetamide, or N-methylpyrrolidone, and the sulfone or sulfoxide solvent is any one or more of sulfolane or dimethyl sulfoxide.

8. The method for preparing the pyrethroid compound containing a benzyl fluoride structure according to claim 4, characterized in that, In step (3), 2,3,5,6-tetrafluoro-4-fluoromethyl-benzyl alcohol is dissolved in toluene and then an acid-binding agent is added. The acyl chloride obtained in step (2) is added dropwise at 0-30°C, and then the reaction is carried out to obtain the pyrethroid compound containing the benzyl fluoride structure described in Formula I. The molar ratio between 2,3,5,6-tetrafluoro-4-fluoromethyl-benzyl alcohol, the acid-binding agent and the acyl chloride is 0.9-1.2:1.0-1.3:

1.

9. The method for preparing the pyrethroid compound containing a benzyl fluoride structure according to claim 8, characterized in that, The acid-binding agent is triethylamine, pyridine, sodium carbonate, potassium carbonate, or liquid alkali.

10. The application of a pyrethroid compound containing a benzyl fluoride structure as described in claim 1, characterized in that: The application of the pyrethroid compounds containing benzyl fluoride structures described in Formula I as insecticides for the control of sanitary pests.

11. The application according to claim 10, characterized in that: The compound of Formula I is used to make mosquito coils or aerosols for the control of resistant mosquitoes and flies.

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