A method for preparing a trifluoroethyl sulfide acaricide intermediate

Abstract

The invention discloses a method for preparing a trifluoroethyl sulfide acaricide intermediate, wherein the method comprises: selecting cheap and readily available 2-fluoroaniline as a starting material, and preparing the intermediate through acetylation, chlorination, sulfonylation, reduction, substitution and hydrolysis, wherein the acetylation and chlorination are completed in one pot. The invention has the advantages of cheap and readily available raw materials, simple operation, short route, high yield, low cost, etc., and has certain application prospects.

Description

Technical Field

[0001] The invention belongs to the field of pesticide chemical synthesis, and specifically relates to a method for preparing 4-chloro-2-fluoro-5-[(2,2,2-trifluoroethyl)sulfanyl]aniline hydrochloride, an intermediate of a trifluoroethyl sulfide acaricide. Background Art

[0002] In recent years, pesticide companies such as BASF and Bayer have successively reported a class of highly active acaricidal compounds containing trifluoroethyl sulfide (sulfoxide) fragments; this class of compounds has a novel structure and good acaricidal activity; there are currently no commercial varieties of this class of compounds, and it is still in the research and development stage. Trifluoroethyl sulfide (sulfoxide) compounds not only have good biological activity against pest mites such as cinnabarinus spider mites and two-spotted spider mites, but also have certain biological activity against brown planthoppers, nematodes, and aphids according to literature; this class of compounds has broad market prospects. The core skeleton of the chemical structure is shown in the figure:

[0003]

[0004] The part other than Q is the essential active part; R1, R2 are generally substituted by halogen, alkyl, etc., among which the most common are R1=Cl, R2=F; n=0 or 1; Q represents the transformation and derivatization of various skeletons.

[0005] The present invention uses 4-chloro-2-fluoro-5-[(2,2,2-trifluoroethyl)sulfanyl]aniline as a key intermediate in the synthesis route of trifluoroethyl sulfide acaricides, wherein 5-amino-2-chloro-4-fluorobenzenethiol is an important intermediate in the synthesis of 4-chloro-2-fluoro-5-[(2,2,2-trifluoroethyl)sulfanyl]aniline, and the specific structural formula is as follows:

[0006]

[0007] There are currently several methods for preparing the trifluoroethyl sulfide acaricide intermediate 4-chloro-2-fluoro-5-[(2,2,2-trifluoroethyl)sulfanyl]aniline or 5-amino-2-chloro-4-fluorobenzenethiol:

[0008] Method 1: Patents JP2915384A, JP8769685A, and JP8769785A propose a method for preparing 5-amino-2-chloro-4-fluorothiophenol: using N-acetyl-4-chloro-2-fluoroaniline as a raw material, chlorosulfonation, reduction, and hydrolysis are performed to obtain 5-amino-2-chloro-4-fluorothiophenol. This method has harsh reaction conditions, the raw materials are not easy to obtain, the risk is high, and the yield is low.

[0009]

[0010] Method 2: Patent US005248822A discloses a method for preparing 5-amino-2-chloro-4-fluorobenzenethiol. This route uses N-acetyl-4-chloro-2-fluoroaniline as a raw material, and uses sulfur monochloride to electrophilically replace the compound N-acetyl-4-chloro-2-fluoroaniline under the catalysis of Lewis acid to obtain bis(2-chloro-4-fluoro-5-acetylaminophenyl) disulfide, and then reduces and hydrolyzes to obtain 5-amino-2-chloro-4-fluorobenzenethiol. The raw materials of this synthetic route are not easy to obtain, the risk is high, the cost is high, and it is not suitable for industrial production.

[0011]

[0012] Method 3: Using 5-acetamido-2-chloro-4-fluorobenzenesulfonyl chloride as raw material, reducing and hydrolyzing to obtain 5-amino-2-chloro-4-fluorobenzenethiophenol. The raw materials of this preparation method are not easy to obtain and the cost is high.

[0013]

[0014] Method 4: Patents WO2014202510, CN105473558, JP2016526539 and US20160145235 propose a method for preparing 4-chloro-2-fluoro-5-[(2,2,2-trifluoroethyl)sulfanyl]aniline. Using p-2-fluoro-4-chloroaniline as a raw material, it undergoes amino protection, chlorosulfonation, and sulfonyl chloride reduction, followed by reaction with trifluoroiodoethane, and finally hydrolysis to obtain 4-chloro-2-fluoro-5-[(2,2,2-trifluoroethyl)sulfanyl]aniline. This route is cumbersome, time-consuming, and costly, and is not suitable for industrial production.

[0015]

[0016] The above methods have many disadvantages: including expensive raw materials or reagents, difficult to obtain, complex reaction operation, harsh conditions, low yield, high risk, etc. Therefore, the development of a new method for preparing 4-chloro-2-fluoro-5-[(2,2,2-trifluoroethyl)sulfanyl]aniline has important research significance and application prospects. Summary of the invention

[0017] In view of the shortcomings of the prior art, the present invention provides a method for preparing 4-chloro-2-fluoro-5-[(2,2,2-trifluoroethyl)sulfanyl]aniline, an intermediate of a trifluoroethyl sulfide acaricide. The method uses 2-fluoroaniline as a starting material, performs acylation, chlorination, chlorosulfonation and reduction, and then reacts with 2,2,2-trifluoroethyl p-toluenesulfonate and hydrolyzes the 4-chloro-2-fluoro-5-[(2,2,2-trifluoroethyl)sulfanyl]aniline hydrochloride.

[0018] The synthetic route of the present invention skillfully completes the two-step reaction of acetylation and chlorination in a "one-pot method", simplifies the reaction operation, shortens the reaction steps, has the advantages of high yield, simple post-treatment, low cost, etc., and at the same time, the raw materials are cheap and easily available, and the reaction is safe, which overcomes the problems of low yield and high risk in the prior art, and has good prospects for industrial application.

[0019] To achieve the above object, the technical solution of the present invention is as follows:

[0020] The present invention provides a method for preparing a trifluoroethyl sulfide acaricide intermediate, the preparation method comprising:

[0021] (1) Compound I (o-fluoroaniline) is reacted with acetyl chloride in an organic solvent and then with sulfonyl chloride to obtain Compound II;

[0022] (2) Compound II is reacted with chlorosulfonic acid under a Lewis acid catalysis under solvent-free conditions to obtain Compound III;

[0023] (3) Compound III is reduced with a reducing agent to obtain compound IV;

[0024] (4) Compound IV is reacted with 2,2,2-trifluoroethyl p-toluenesulfonate in an organic solvent under the action of an inorganic base and hydrolyzed to obtain the target product V;

[0025]

[0026] Specifically, the preparation method comprises the following steps:

[0027] (1) Compound I is dissolved in an organic solvent A, acetyl chloride is added at -10 to 30°C (preferably -5 to 5°C), the temperature is raised to 30 to 80°C (preferably 50 to 60°C) for a first reaction of 3 to 10 hours (preferably 6 hours), sulfonyl chloride is added at 20 to 60°C (preferably 50 to 55°C), the temperature is raised to reflux temperature for a second reaction of 2 to 6 hours (preferably 3 hours), and the resulting reaction solution A is subjected to post-treatment A to obtain compound II;

[0028]

[0029] The molar ratio of the compound I, acetyl chloride and sulfonyl chloride is 1:1-2:1-2, preferably 1:1.2:1.5;

[0030] (2) dissolving the compound II described in step (1) in chlorosulfonic acid, adding Lewis acid, reacting at 60-100° C. (preferably 70-80° C.) for 2-8 h (preferably 5 h), and subjecting the obtained reaction solution B to post-treatment B to obtain compound III;

[0031]

[0032] The molar ratio of the compound II, chlorosulfonic acid and Lewis acid is 1:2-5:1-3, preferably 1:3:2;

[0033] The Lewis acid is selected from one or a mixture of two of ferric chloride, aluminum chloride, tin tetrachloride, titanium tetrachloride, and zinc dichloride, preferably aluminum chloride;

[0034] (3) dissolving the compound III described in step (2) in an acid, adding a reducing agent, heating under reflux for a reaction of 4 to 10 h (preferably 6 h), and subjecting the obtained reaction solution C to post-treatment C to obtain compound IV; the reducing agent is selected from zinc powder, tin powder, tin dichloride or a mixture of two thereof, preferably zinc powder;

[0035]

[0036] The molar ratio of the compound III to the reducing agent is 1:1 to 10, preferably 1:5;

[0037] (4) dissolving the compound IV described in step (3) in an organic solvent B, adding an alkaline substance and 2,2,2-trifluoroethyl p-toluenesulfonate, stirring and reacting at 60-100° C. (preferably 70-80° C.) for 1-10 h (preferably 6 h), cooling to room temperature (20-30° C.), adding hydrochloric acid (concentrated hydrochloric acid in one embodiment of the present invention) to adjust the pH to 1-2, and subjecting the obtained reaction solution D to post-treatment D to obtain a trifluoroethyl sulfide acaricide intermediate represented by formula V;

[0038]

[0039] The molar ratio of the compound IV, the alkaline substance and 2,2,2-trifluoroethyl p-toluenesulfonate is 1:1-4:1-3, preferably 1:2:1.5.

[0040] Furthermore, the organic solvent A in step (1) is selected from one or a mixed solvent of dichloromethane, dichloroethane, chloroform, and carbon tetrachloride, preferably dichloroethane.

[0041] Furthermore, the volume of the organic solvent A in step (1) is 0.33 to 1 mL / mmol, preferably 0.5 mL / mmol, based on the amount of the compound I.

[0042] Furthermore, the post-treatment A in step (1) is: stirring the reaction solution A at -10 to 10°C (preferably -5 to 5°C) for 0.5 to 3h (preferably 1h), the product precipitates, and is filtered off with suction, and the resulting filter cake is dried (at 55°C) to obtain the compound II.

[0043] Furthermore, the post-treatment B in step (2) is: dropping the reaction solution B into ice water, extracting with ethyl acetate, combining the organic phases, drying over anhydrous sodium sulfate, and concentrating under reduced pressure to obtain compound III.

[0044] Furthermore, the mass ratio of the compound II to the ice water is 1:10.

[0045] Furthermore, the acid in step (3) is selected from HCl, sulfuric acid, acetic acid or a mixture of two or more thereof, preferably acetic acid;

[0046] Further, in step (3), the volume of the acid is 1 to 5 mL / mmol, preferably 3 mL / mmol, based on the amount of compound III;

[0047] Furthermore, in step (3), the post-treatment C is: cooling the reaction solution C to room temperature (20-30° C.), adding water, adding ethyl acetate for extraction (three times), combining the organic phases, drying over anhydrous sodium sulfate, and concentrating under reduced pressure to obtain compound IV.

[0048] Furthermore, the volume ratio of the water to the acid is 2:1.

[0049] Furthermore, the alkaline substance in step (4) is selected from one or a mixture of two or more of sodium hydroxide, potassium hydroxide, potassium carbonate, and potassium bicarbonate, preferably potassium hydroxide;

[0050] Furthermore, the organic solvent B in step (4) is selected from one or a mixed solvent of two or more selected from ethanol, methanol, acetonitrile, and N,N-dimethylformamide, preferably ethanol.

[0051] Furthermore, the volume of the organic solvent B in step (4) is 0.5-2 mL / mmol, preferably 1 mL / mmol, based on the amount of compound IV.

[0052] Furthermore, the post-treatment D in step (4) is: filtering the reaction solution D, and drying the obtained filter cake (in the embodiment of the present invention, drying at 55° C.) to obtain the trifluoroethyl sulfide acaricide intermediate represented by formula V.

[0053] Compared with the prior art, the present invention has the following beneficial effects:

[0054] The synthetic route of the present invention skillfully completes the two-step reaction of acetylation and chlorination in one pot, optimizes the reaction conditions, has the advantages of fewer reaction steps and high yield, and at the same time, the raw materials are cheap and easily available, the operation is simple and safe, and the problems of low yield and high risk in the prior art are overcome, thereby obtaining a better synthetic route with a higher total yield and certain innovation and practicality. DETAILED DESCRIPTION

[0055] The present invention is further described below by means of specific embodiments, but the protection scope of the present invention is not limited thereto.

[0056] Example 1: Preparation of Compound II

[0057] Add compound I (5g, 45mmol) to a dry round-bottom flask, add dichloroethane (22.5mL) and stir to dissolve, add acetyl chloride (4.24g, 54mmol) dropwise at -5 to 5°C, heat to 55°C and react for 6h, then slowly add sulfonyl chloride (9.11g, 67.5mmol) dropwise, heat to reflux temperature (85°C) and react for 3h, and monitor the reaction by TLC. After the reaction is completed, cool to 0°C and stir for 1h, crystallize, filter, and dry the filter cake at 55°C to obtain a white solid (7.41g), with a reaction yield of 88% and a product purity of 98%. White solid, mp147-149°C; R f =0.39 (petroleum ether (PE): ethyl acetate (EA) = 3:1); 1 H NMR (500MHz, DMSO-d6): δ = 9.84 (s, 1H), 7.92-7.95 (t, J = 8.5Hz, 1H), 7.45-7.47 (d, J = 10.65Hz, 1H), 7.23-7.25 (d, J = 8.85Hz, 1H), 2.09 (s, 3H) ppm.

[0058] Example 2: Preparation of Compound II

[0059] Compound I (5 g, 45 mmol) was added to a dry round-bottom flask, and dichloroethane (22.5 mL) was added to stir and dissolve, and acetyl chloride (3.53 g, 45 mmol) was added dropwise at -5 to 5 ° C, and the temperature was raised to 55 ° C for 6 h, followed by slow dropwise addition of sulfonyl chloride (6.08 g, 45 mmol), and the temperature was raised to reflux temperature (85 ° C) for 3 h, and the reaction was detected by TLC. After the reaction was completed, the temperature was lowered to 0 ° C and stirred for 1 h, and the filter cake was dried at 55 ° C to obtain a white solid (5.89 g), with a reaction yield of 70% and a product purity of 98%. The characterization data of the obtained white solid were consistent with those in Example 1.

[0060] Example 3: Preparation of Compound II

[0061] Compound I (5 g, 45 mmol) was added to a dry round-bottom flask, and dichloroethane (22.5 mL) was added to stir and dissolve, and acetyl chloride (7.07 g, 90 mmol) was added dropwise at -5 to 5 ° C, and the temperature was raised to 55 ° C for 6 h, followed by slow dropwise addition of sulfonyl chloride (12.15 g, 90 mmol), and the temperature was raised to reflux temperature (85 ° C) for 3 h, and the reaction was detected by TLC. After the reaction was completed, the temperature was lowered to 0 ° C and stirred for 1 h, and the filter cake was dried at 55 ° C to obtain a white solid (7.24 g), with a reaction yield of 86% and a product purity of 97.6%. The characterization data of the obtained white solid were consistent with those in Example 1.

[0062] Example 4: Preparation of Compound III

[0063] Take a dry round-bottom flask, add compound II (5g, 26.74mmol) and chlorosulfonic acid (9.35g, 80.22mmol), add anhydrous aluminum chloride (7.13g, 53.48mmol), heat to 80℃ and stir for 5h, and detect the reaction by TLC. After the reaction is completed, cool to room temperature (20-30℃), and slowly add the reaction solution dropwise to 50g ice water under stirring. Add 25mL ethyl acetate to extract twice, combine the organic phases, add anhydrous sodium sulfate to dry, and concentrate under reduced pressure to obtain an off-white solid (6.48g), with a reaction yield of 85% and a product purity of 97%.

[0064] Example 5: Preparation of Compound III

[0065] Take a dry round-bottom flask, add compound II (5g, 26.74mmol) and chlorosulfonic acid (6.23g, 53.48mmol), add anhydrous aluminum chloride (3.57g, 26.74mmol), heat to 80℃ and stir for 5h, and detect the reaction by TLC. After the reaction is completed, cool to room temperature (20-30℃), and slowly add the reaction solution dropwise to 50g ice water under stirring. Add 25mL ethyl acetate to extract twice, combine the organic phases, add anhydrous sodium sulfate to dry, and concentrate under reduced pressure to obtain an off-white solid (5.26g), with a reaction yield of 69% and a product purity of 97%.

[0066] Example 6: Preparation of Compound III

[0067] Take a dry round-bottom flask, add compound II (5g, 26.74mmol) and chlorosulfonic acid (15.58g, 133.7mmol), add anhydrous aluminum chloride (10.70g, 80.22mmol), heat to 80℃ and stir for 5h, and detect the reaction by TLC. After the reaction is completed, cool to room temperature (20-30℃), and slowly add the reaction solution dropwise to 50g ice water under stirring. Add 25mL ethyl acetate to extract twice, combine the organic phases, add anhydrous sodium sulfate to dry, and concentrate under reduced pressure to obtain an off-white solid (6.25g), with a reaction yield of 82% and a product purity of 98%.

[0068] Example 7: Preparation of Compound III

[0069] Take a dry round-bottom flask, add compound II (5g, 26.74mmol) and chlorosulfonic acid (9.35g, 80.22mmol), add anhydrous ferric chloride (8.67g, 53.48mmol), heat to 80℃ and stir for 5h, and detect the reaction by TLC. After the reaction is completed, cool to room temperature (20-30℃), and slowly add the reaction solution dropwise to 50g ice water under stirring. Add 25mL ethyl acetate to extract twice, combine the organic phases, add anhydrous sodium sulfate to dry, and concentrate under reduced pressure to obtain an off-white solid (4.95g), with a reaction yield of 65% and a product purity of 96%.

[0070] Example 8: Preparation of Compound III

[0071] Take a dry round-bottom flask, add compound II (5g, 26.74mmol) and chlorosulfonic acid (9.35g, 80.22mmol), add anhydrous tin tetrachloride (13.93g, 53.48mmol), heat to 80℃ and stir for 5h, and detect the reaction by TLC. After the reaction is completed, cool to room temperature (20-30℃), and slowly add the reaction solution dropwise to 50g ice water under stirring. Add 25mL ethyl acetate to extract twice, combine the organic phases, add anhydrous sodium sulfate to dry, and concentrate under reduced pressure to obtain an off-white solid (5.33g), with a reaction yield of 70% and a product purity of 95%.

[0072] Example 9: Preparation of Compound III

[0073] Take a dry round-bottom flask, add compound II (5g, 26.74mmol) and chlorosulfonic acid (9.35g, 80.22mmol), add anhydrous titanium tetrachloride (10.15g, 53.48mmol), heat to 80℃ and stir for 5h, and detect the reaction by TLC. After the reaction is completed, cool to room temperature (20-30℃), and slowly add the reaction solution dropwise to 50g ice water under stirring. Add 25mL ethyl acetate to extract twice, combine the organic phases, add anhydrous sodium sulfate to dry, and concentrate under reduced pressure to obtain an off-white solid (3.96g), with a reaction yield of 52% and a product purity of 95%.

[0074] Example 10: Preparation of Compound III

[0075] Take a dry round-bottom flask, add compound II (5g, 26.74mmol) and chlorosulfonic acid (9.35g, 80.22mmol), add anhydrous zinc dichloride (7.29g, 53.48mmol), heat to 80℃ and stir for 5h, and detect the reaction by TLC. After the reaction is completed, cool to room temperature (20-30℃), and slowly add the reaction solution dropwise to 50g ice water under stirring. Add 25mL ethyl acetate to extract twice, combine the organic phases, add anhydrous sodium sulfate to dry, and concentrate under reduced pressure to obtain an off-white solid (5.71g), with a reaction yield of 75% and a product purity of 97%.

[0076] Example 11: Preparation of Compound IV

[0077] Add compound III (5 g, 17.5 mmol) to a dry round-bottom flask, add acetic acid (50 mL) and stir to dissolve, add zinc powder (5.72 g, 87.5 mmol) in batches at room temperature, heat to reflux temperature (120 ° C) and react for 6 hours, and detect the reaction by TLC. After the reaction is completed, cool to room temperature, add 100 mL of water, then extract twice with 50 mL of ethyl acetate, combine the organic phases, add anhydrous sodium sulfate to dry, and concentrate under reduced pressure to obtain a light yellow solid (3.18 g), the reaction yield is 83%, and the product purity is 96%.

[0078] Example 12: Preparation of Compound IV

[0079] Add compound III (5 g, 17.5 mmol) to a dry round-bottom flask, add acetic acid (50 mL) and stir to dissolve, add zinc powder (1.14 g, 17.5 mmol) in batches at room temperature, heat to reflux temperature and react for 6 h, and detect the reaction by TLC. After the reaction is completed, cool to room temperature, add 100 mL of water, then extract twice with 50 mL of ethyl acetate, combine the organic phases, add anhydrous sodium sulfate to dry, and concentrate under reduced pressure to obtain a light yellow solid (2.03 g), the reaction yield is 53%, and the product purity is 95%.

[0080] Example 13: Preparation of Compound IV

[0081] Add compound III (5 g, 17.5 mmol) to a dry round-bottom flask, add acetic acid (50 mL) and stir to dissolve, add zinc powder (11.4 g, 175 mmol) in batches at room temperature, heat to reflux temperature (120 ° C) and react for 6 hours, and detect the reaction by TLC. After the reaction is completed, cool to room temperature, add 100 mL of water, then extract twice with 50 mL of ethyl acetate, combine the organic phases, add anhydrous sodium sulfate to dry, and concentrate under reduced pressure to obtain a light yellow solid (3.07 g), the reaction yield is 80%, and the product purity is 98%.

[0082] Example 14: Preparation of Compound IV

[0083] Add compound III (5 g, 17.5 mmol) to a dry round-bottom flask, add acetic acid (50 mL) and stir to dissolve, add tin powder (10.39 g, 87.5 mmol) in batches at room temperature, heat to reflux temperature (120 ° C) and react for 6 hours, and detect the reaction by TLC. After the reaction is completed, cool to room temperature, add 100 mL of water, then extract twice with 50 mL of ethyl acetate, combine the organic phases, add anhydrous sodium sulfate to dry, and concentrate under reduced pressure to obtain a light yellow solid (2.91 g), the reaction yield is 76%, and the product purity is 97%.

[0084] Example 15: Preparation of Compound IV

[0085] Add compound III (5 g, 17.5 mmol) to a dry round-bottom flask, add acetic acid (50 mL) and stir to dissolve, add tin dichloride (16.59 g, 87.5 mmol) in batches at room temperature, heat to reflux temperature (120 ° C) and react for 6 hours, and detect the reaction by TLC. After the reaction is completed, cool to room temperature, add 100 mL of water, then extract twice with 50 mL of ethyl acetate, combine the organic phases, add anhydrous sodium sulfate to dry, and concentrate under reduced pressure to obtain a light yellow solid (3.03 g), the reaction yield is 79%, and the product purity is 97.5%.

[0086] Example 16: Preparation of Compound IV

[0087] Add compound III (5 g, 17.5 mmol) to a dry round-bottom flask, add concentrated hydrochloric acid (50 mL) and stir to dissolve, add zinc powder (5.72 g, 87.5 mmol) in batches at room temperature, heat to reflux temperature (110 ° C) and react for 6 hours, and detect the reaction by TLC. After the reaction is completed, cool to room temperature, add 100 mL of water, then extract twice with 50 mL of ethyl acetate, combine the organic phases, add anhydrous sodium sulfate to dry, and concentrate under reduced pressure to obtain a light yellow solid (2.84 g), the reaction yield is 74%, and the product purity is 96%.

[0088] Example 17: Preparation of Compound IV

[0089] Add compound III (5 g, 17.5 mmol) to a dry round-bottom flask, add sulfuric acid (50 mL) and stir to dissolve, add zinc powder (5.72 g, 87.5 mmol) in batches at room temperature, heat to reflux temperature (110 ° C) and react for 6 hours, and detect the reaction by TLC. After the reaction is completed, cool to room temperature, add 100 mL of water, and then extract twice with 50 mL of ethyl acetate, combine the organic phases, add anhydrous sodium sulfate to dry, and concentrate under reduced pressure to obtain a light yellow solid (2.64 g), the reaction yield is 69%, and the product purity is 97%.

[0090] Example 18: Preparation of Compound V

[0091] Take a single-mouth round-bottom flask, add compound IV (5g, 22.83mmol) and ethanol (20mL) at room temperature (20-30°C), stir and dissolve, then add potassium hydroxide (2.56g, 45.66mmol) and 2,2,2-trifluoroethyl p-toluenesulfonate (8.71g, 34.25mmol), heat to 75°C and stir to react for 6h, and detect the reaction by TLC. After the reaction is completed, cool to room temperature (20-30°C), add concentrated hydrochloric acid, adjust the pH to 1-2, filter by suction, and dry the filter cake to obtain a light gray solid (5.26g), the reaction yield is 89%, and the product purity is 98.5%.

[0092] Light grey solid, mp162-164℃; R f =0.75(PE:EA=3:1); 1 H NMR (500MHz, DMSO-d6): δ = 7.85 (s, 3H), 7.40-7.43 (d, J = 10.6Hz, 1H), 7.29-7.31 (d, J = 8.7Hz, 1H), 3.87-3.93 (q, J = 10.25Hz, 2H) ppm.

[0093] Example 19: Preparation of Compound V

[0094] Take a single-mouth round-bottom flask, add compound IV (5g, 22.83mmol) and ethanol (20mL) at room temperature (20-30°C), stir and dissolve, then add potassium hydroxide (1.92g, 34.25mmol) and 2,2,2-trifluoroethyl p-toluenesulfonate (5.81g, 22.83mmol) in sequence, heat to 75°C and stir to react for 6h, and detect the reaction by TLC. After the reaction is completed, cool to room temperature (20-30°C), add concentrated hydrochloric acid, adjust the pH to 1-2, filter, and dry the filter cake to obtain a light gray solid (4.02g), the reaction yield is 68%, and the product purity is 97%. The characterization data of the obtained light gray solid are consistent with those of Example 18.

[0095] Example 20: Preparation of Compound V

[0096] Take a single-mouth round-bottom flask, add compound IV (5g, 22.83mmol) and ethanol (20mL) at room temperature (20-30°C), stir and dissolve, then add potassium hydroxide (3.84g, 68.50mmol) and 2,2,2-trifluoroethyl p-toluenesulfonate (17.41g, 68.49mmol) in sequence, heat to 75°C and stir to react for 6h, and detect the reaction by TLC. After the reaction is completed, cool to room temperature (20-30°C), add concentrated hydrochloric acid, adjust the pH to 1-2, filter, and dry the filter cake to obtain a light gray solid (5.09g), the reaction yield is 86%, and the product purity is 98.6%. The characterization data of the obtained light gray solid are consistent with those of Example 18.

[0097] Example 21: Preparation of Compound V

[0098] Take a single-mouth round-bottom flask, add compound IV (5g, 22.83mmol) and ethanol (20mL) at room temperature (20-30°C), stir and dissolve, then add sodium hydroxide (1.83g, 45.66mmol) and 2,2,2-trifluoroethyl p-toluenesulfonate (8.71g, 34.25mmol) in sequence, heat to 75°C and stir to react for 6h, and detect the reaction by TLC. After the reaction is completed, cool to room temperature (20-30°C), add concentrated hydrochloric acid, adjust the pH to 1-2, filter by suction, and dry the filter cake to obtain a light gray solid (4.91g), with a reaction yield of 83% and a product purity of 98%. The characterization data of the obtained light gray solid are consistent with those of Example 18.

[0099] Example 22: Preparation of Compound V

[0100] Take a single-mouth round-bottom flask, add compound IV (5g, 22.83mmol) and ethanol (20mL) at room temperature (20-30°C), stir and dissolve, then add potassium bicarbonate (4.57g, 45.66mmol) and 2,2,2-trifluoroethyl p-toluenesulfonate (8.71g, 34.25mmol) in sequence, heat to 75°C and stir to react for 6h, and detect the reaction by TLC. After the reaction is completed, cool to room temperature (20-30°C), add concentrated hydrochloric acid, adjust the pH to 1-2, filter, and dry the filter cake to obtain a light gray solid (4.08g), the reaction yield is 69%, and the product purity is 97%. The characterization data of the obtained light gray solid are consistent with those of Example 18.

[0101] Example 23: Preparation of Compound V

[0102] Take a single-mouth round-bottom flask, add compound IV (5g, 22.83mmol) and ethanol (20mL) at room temperature (20-30°C), stir and dissolve, then add potassium carbonate (6.31g, 45.66mmol) and 2,2,2-trifluoroethyl p-toluenesulfonate (8.71g, 34.25mmol), heat to 75°C and stir to react for 6h, and detect the reaction by TLC. After the reaction is completed, cool to room temperature (20-30°C), add concentrated hydrochloric acid, adjust the pH to 1-2, filter, and dry the filter cake to obtain a light gray solid (4.49g), the reaction yield is 76%, and the product purity is 97%. The characterization data of the obtained light gray solid are consistent with those of Example 18.

[0103] Example 24: Preparation of Compound V

[0104] Take a single-mouth round-bottom flask, add compound IV (5g, 22.83mmol) and methanol (20mL) at room temperature (20-30°C), stir and dissolve, then add potassium hydroxide (2.56g, 45.66mmol) and 2,2,2-trifluoroethyl p-toluenesulfonate (8.71g, 34.25mmol) in sequence, heat to 75°C and stir to react for 6h, and detect the reaction by TLC. After the reaction is completed, cool to room temperature (20-30°C), add concentrated hydrochloric acid, adjust the pH to 1-2, filter, and dry the filter cake to obtain a light gray solid (4.73g), the reaction yield is 80%, and the product purity is 98%. The characterization data of the obtained light gray solid are consistent with those of Example 18.

[0105] It should be pointed out that the above embodiments are only for illustrating the concept and features of the present invention, and their purpose is to allow those skilled in the art to understand the experiment and implement it accordingly, and they cannot limit the protection scope of the present invention. Any equivalent changes or modifications made according to the spirit and essence of the present invention should be included in the protection scope of the present invention.

Claims

1. A method for preparing a trifluoroethyl sulfide acaricide intermediate, characterized in that The preparation method comprises the following steps: (1) Compound I is dissolved in an organic solvent A, acetyl chloride is added at -10 to 30°C, the temperature is raised to 30 to 80°C for a first reaction of 3 to 10 hours, sulfonyl chloride is added at 20 to 60°C, the temperature is raised to reflux temperature for a second reaction of 2 to 6 hours, and the resulting reaction solution A is subjected to post-treatment A to obtain compound II; The molar ratio of the compound I, acetyl chloride and sulfonyl chloride is 1:1-2:1-2; (2) dissolving the compound II described in step (1) in chlorosulfonic acid, adding Lewis acid, reacting at 60-100° C. for 2-8 h, and subjecting the obtained reaction solution B to post-treatment B to obtain compound III; The molar ratio of the compound II, chlorosulfonic acid and Lewis acid is 1:2-5:1-3; The Lewis acid is selected from one or a mixture of two of ferric chloride, aluminum chloride, tin tetrachloride, titanium tetrachloride, and zinc dichloride; (3) dissolving the compound III described in step (2) in an acid, adding a reducing agent, heating and refluxing for 4 to 10 hours, and subjecting the obtained reaction solution C to post-treatment C to obtain compound IV; the reducing agent is selected from zinc powder, tin powder, tin dichloride, or a mixture of two thereof; The molar ratio of the compound III to the reducing agent is 1:1 to 10; (4) dissolving the compound IV described in step (3) in an organic solvent B, adding an alkaline substance and 2,2,2-trifluoroethyl p-toluenesulfonate, stirring and reacting at 60-100° C. for 1-10 hours, cooling to room temperature, adding hydrochloric acid to adjust the pH to 1-2, and subjecting the obtained reaction solution D to post-treatment D to obtain a trifluoroethyl sulfide acaricide intermediate represented by formula V; The molar ratio of the compound IV, the alkaline substance and 2,2,2-trifluoroethyl p-toluenesulfonate is 1:1-4:1-3.

2. The method for preparing a trifluoroethyl sulfide acaricide intermediate according to claim 1, characterized in that: The organic solvent A in step (1) is selected from one or a mixed solvent of two or more selected from dichloromethane, dichloroethane, chloroform and carbon tetrachloride; The volume of the organic solvent A in step (1) is 0.33-1 mL / mmol based on the amount of the compound I.

3. The method for preparing a trifluoroethyl sulfide acaricide intermediate according to claim 1, characterized in that: The post-treatment A in step (1) is as follows: stirring the reaction solution A at -10 to 10°C for 0.5 to 3h, the product precipitates, and is filtered off with suction, and the filter cake is dried to obtain the compound II.

4. The method for preparing a trifluoroethyl sulfide acaricide intermediate according to claim 1, characterized in that: The post-treatment B in step (2) is: dropping the reaction solution B into ice water, extracting with ethyl acetate, combining the organic phases, drying over anhydrous sodium sulfate, and concentrating under reduced pressure to obtain compound III.

5. The method for preparing a trifluoroethyl sulfide acaricide intermediate according to claim 1, characterized in that: The acid in step (3) is selected from HCl, sulfuric acid, acetic acid, or a mixture of two or more thereof.

6. The method for preparing a trifluoroethyl sulfide acaricide intermediate according to claim 1, characterized in that: In step (3), the volume of the acid is 1 to 5 mL / mmol based on the amount of compound III.

7. The method for preparing a trifluoroethyl sulfide acaricide intermediate according to claim 1, characterized in that: In step (3), the post-treatment C is: cooling the reaction solution C to room temperature, adding water, adding ethyl acetate for extraction, combining the organic phases, drying over anhydrous sodium sulfate, and concentrating under reduced pressure to obtain compound IV.

8. The method for preparing a trifluoroethyl sulfide acaricide intermediate according to claim 1, characterized in that: The alkaline substance in step (4) is selected from one or a mixture of two or more of sodium hydroxide, potassium hydroxide, potassium carbonate and potassium bicarbonate.

9. The method for preparing a trifluoroethyl sulfide acaricide intermediate according to claim 1, characterized in that: The organic solvent B in step (4) is selected from one or a mixed solvent of two or more selected from ethanol, methanol, acetonitrile, and N,N-dimethylformamide; The volume of the organic solvent B in step (4) is 0.5-2 mL / mmol based on the amount of compound IV.

10. The method for preparing a trifluoroethyl sulfide acaricide intermediate according to claim 1, characterized in that: The post-treatment D in step (4) is: filtering the reaction solution D, drying the obtained filter cake, and obtaining the trifluoroethyl sulfide acaricide intermediate represented by formula V.

Images