Phenyl sulfide (sulfoxide) compound and application thereof

Abstract

The invention belongs to the field of agricultural acaricides. In particular to a phenyl sulfide (sulfoxide) compound and application thereof. The structure is as shown in a general formula I; the definition of each substituent group in the formula is shown in the specification. The compound as shown in the general formula I has excellent acaricidal activity and can be used for preventing and treating various pest mites.

Description

[0001] This application is a divisional application of the Chinese Invention Patent Application with the application number 202510310343.6, the application date of March 17, 2025, and the invention name of "A phenyl sulfide (sulfoxide) compound and its application". TECHNICAL FIELD

[0002] The present application belongs to the field of agricultural acaricides, and specifically relates to a phenyl sulfide (sulfoxide) compound and its application. BACKGROUND

[0003] The following compounds KC1 (compound 3), KC2 (compound 21), KC3 (compound 4), KC4 (compound 22), KC5 (compound 1), and KC6 (compound 19) are disclosed in patent CN114957062A and have good acaricidal activity: .

[0004] The compound as shown in the general formula I of the present application and its acaricidal activity have not been reported in the prior art. Compared with the prior art, the compound of the present application has higher acaricidal activity. SUMMARY

[0005] The purpose of the present application is to provide a phenyl sulfide (sulfoxide) compound with better acaricidal effect, which can be applied in the fields of agriculture, forestry, and health to control pests and mites.

[0006] The technical solution of the present application is as follows: A phenyl sulfide (sulfoxide) compound, as shown in the general formula I:

[0007] In the general formula I, R1 is selected from chlorine, bromine, or cyano; R3 is selected from chlorine, bromine, or cyano; R2 is selected from -CF3, -CHF2, -CH2F, -CH2CF3, -CH2CHF2, or -CH2CH2F; n is selected from 0 or 1.

[0008] In one possible implementation, in the general formula I, R1 is selected from chlorine; R3 is selected from chlorine, bromine, or cyano; R2 is selected from -CF3, -CHF2, -CH2F, -CH2CF3, -CH2CHF2, or -CH2CH2F; n is selected from 0 or 1.

[0009] In one possible implementation, in the general formula I, R1 is selected from bromine; R3 is selected from chlorine, bromine, or cyano groups; R2 is selected from -CF3, -CHF2, -CH2F, -CH2CF3, -CH2CHF2, or -CH2CH2F; n is selected from 0 or 1.

[0010] In one possible implementation, in general formula I, R1 is selected from cyano groups; R3 is selected from chlorine, bromine, or cyano groups; R2 is selected from -CF3, -CHF2, -CH2F, -CH2CF3, -CH2CHF2, or -CH2CH2F; n is selected from 0 or 1.

[0011] In one possible implementation, the compound of general formula I of the present invention is selected from the following specific compounds: .

[0012] In the above technical solutions, halogen refers to fluorine, chlorine, bromine or iodine.

[0013] Some of the compounds of general formula I in this invention are shown below, but this invention is by no means limited to these compounds.

[0014]

[0015] In general formula I, when R1 = Cl and R3 = Cl, R2 represents different substituents and n represents different values, as shown in Table 1, representing compounds numbered 1.1-1.12.

[0016] Table 1 .

[0017] In general formula I, when R1 = Cl and R3 = Br, R2 is a different substituent and n is a different value consistent with Table 1, representing compounds numbered 2.1-2.12, corresponding to 1.1-1.12 in Table 1.

[0018] In general formula I, when R1 = Cl and R3 = CN, R2 is a different substituent and n is a different value consistent with Table 1, representing compounds numbered 3.1-3.12, corresponding to 1.1-1.12 in Table 1.

[0019] In general formula I, when R1 = Br and R3 = Cl, R2 is a different substituent and n is a different value, consistent with Table 1, representing compounds numbered 4.1-4.12, corresponding to 1.1-1.12 in Table 1.

[0020] In general formula I, when R1 = Br and R3 = Br, R2 is a different substituent and n is a different value, consistent with Table 1, representing compounds numbered 5.1-5.12, corresponding to 1.1-1.12 in Table 1.

[0021] In general formula I, when R1 = Br and R3 = CN, R2 is a different substituent and n is a different value consistent with Table 1, representing compounds numbered 6.1-6.12, corresponding to 1.1-1.12 in Table 1.

[0022] In general formula I, when R1 = CN and R3 = Cl, R2 is a different substituent and n is a different value, consistent with Table 1, representing compounds numbered 7.1-7.12, corresponding to 1.1-1.12 in Table 1.

[0023] In general formula I, when R1 = CN and R3 = Br, R2 is a different substituent and n is a different value consistent with Table 1, representing compounds numbered 8.1-8.12, corresponding to 1.1-1.12 in Table 1.

[0024] In general formula I, when R1 = CN and R3 = CN, R2 is a different substituent and n is a different value consistent with Table 1, representing compounds numbered 9.1-9.12, corresponding to 1.1-1.12 in Table 1.

[0025] The compound of general formula I of the present invention can be prepared according to the following scheme, unless otherwise specified, the definitions of each group in the formula are the same as above.

[0026]

[0027] Starting with amino compound IX, it reacts with trifluoroacetic anhydride under normal conditions to obtain amino-protected amide compound VIII, which is further reacted with chlorosulfonic acid under heating conditions to obtain phenylsulfonyl chloride VII.

[0028] Sulfonyl chloride compound VII yields phenylthiophenol compound VI in the presence of a reducing agent. The reaction is typically carried out at 0–150 °C (e.g., 140 °C, 130 °C, 120 °C, 110 °C, 100 °C, 90 °C, 80 °C, 70 °C, 60 °C, 50 °C, 30 °C). The reaction time is typically 0.5–48 hours. The reducing agent can be red phosphorus, zinc, iron, copper, nickel, or a mixture of red phosphorus, zinc, iron, copper, and nickel in any proportion; the molar ratio of compound VII to the reducing agent is 1:1–30 (e.g., 1:1–25, 1:1–20, 1:1–10, 1:1–9, 1:1–8, 1:1–7, 1:1–6, 1:1–5, 1:1–4, 1:1–3, 1:1–2). The reaction can be carried out with appropriate amounts of organic or inorganic acids such as formic acid, acetic acid, trifluoroacetic acid, hydrochloric acid, sulfuric acid or nitric acid; the molar ratio of compound of general formula VII to acid is 1:1-100 (e.g. 1:1-90, 1:1-80, 1:1-70, 1:1-60, 1:1-50, 1:1-40, 1:1-30, 1:1-20, 1:1-10, 1:1-9, 1:1-8, 1:1-7, 1:1-6, 1:1-5, 1:1-4, 1:1-3, 1:1-2).

[0029] Preferably, red phosphorus and iodine are further added in this reaction step.

[0030] Compound VI is hydrolyzed under normal conditions in acidic or alkaline conditions to yield intermediate aniline V.

[0031] Compounds of general formula V can be reacted with halogenated reagents or sulfonates in a suitable solvent and in the presence of a suitable base to prepare compounds of general formula IV. The halogenating agent can be 2,2,2-trifluoroiodoethane, 2,2-difluoroiodoethane, etc., and the sulfonate can be 2,2,2-trifluoroethyl methanesulfonate, 2,2,2-trifluoroethyl benzenesulfonate, or ethyl 2,2,2-trifluorop-toluenesulfonate, etc.; the molar ratio of compound of general formula V to the halogenating agent or sulfonate is 1:1-100 (e.g., 1:1-90, 1:1-80, 1:1-70, 1:1-60, 1:1-50, 1:1-40, 1:1-30, 1:1-20, 1:1-10, 1:1-9, 1:1-8, 1:1-7, 1:1-6, 1:1-5, 1:1-4, 1:1-3, 1:1-2). Suitable bases, which may be the same or different, include trimethylamine, triethylamine, pyridine, DBU, and 4-dimethylaminopyridine. N , N- Organic bases such as diisopropylethylamine, alkali metal hydrides such as sodium hydride and potassium hydride, alkali metal hydroxides such as sodium hydroxide and potassium hydroxide, alkaline earth metal hydroxides such as calcium hydroxide, alkali metal carbonates such as sodium carbonate and potassium carbonate, alkali metal bicarbonates such as sodium bicarbonate, and metal alkoxides such as sodium methoxide, sodium ethoxide, potassium ethoxide, potassium tert-butoxide, and sodium tert-butoxide; the molar ratio of compound of general formula VI to base is 1:1-20 (e.g., 1:1-18, 1:1-16, 1:1-14, 1:1-12, 1:1-10, 1:1-9, 1:1-8, 1:1-7, 1:1-6, 1:1-5, 1:1-4, 1:1-3, 1:1-2). Suitable solvents can be the same or different, including aromatic hydrocarbons such as benzene, toluene, and xylene; ketones such as acetone, methyl ethyl ketone, and methyl isobutyl ketone; halogenated hydrocarbons such as chloroform and dichloromethane; esters such as methyl acetate and ethyl acetate; ethers such as tetrahydrofuran, dioxane, diethyl ether, 1,2-dimethoxyethane, and 1,4-dioxane; and water, acetonitrile, etc. N , N -Dimethylformamide, N Polar solvents such as methylpyrrolidone, dimethyl sulfoxide, or mixtures thereof are used. The reaction is typically carried out at 0°C to the boiling point of the solvent. The reaction time is typically 0.5–48 hours.

[0032] Compounds of general formula IV react with sodium nitrite, one or more acids, and potassium iodide to prepare compounds of general formula III. The acids can be inorganic or organic, such as hydrochloric acid, hydrobromic acid, sulfuric acid, phosphoric acid, formic acid, acetic acid, propionic acid, butyric acid, valeric acid, trifluoroacetic acid, oxalic acid, malonic acid, or methanesulfonic acid. The reaction solvent can be water, chloroform, dichloromethane, carbon tetrachloride, hexane, benzene, toluene, ethyl acetate, DMF, tetrahydrofuran, or dioxane. The reaction is usually carried out at temperatures between 0 and 100°C. The reaction time is typically between 0.5 and 48 hours.

[0033] Compound of general formula III reacts with substituted phenylboronic acid II in a suitable solvent, a suitable base, and a suitable palladium catalyst at temperatures ranging from -10°C to the solvent boiling point for 0.5–48 hours to yield compound of general formula I-1. Suitable solvents include water, dichloromethane, chloroform, carbon tetrachloride, hexane, benzene, toluene, acetonitrile, tetrahydrofuran, dioxane, DMF, or DMSO. Suitable bases include hydrides of alkali metals such as lithium, sodium, or potassium (e.g., sodium hydride, potassium hydride), hydroxides of alkali metals such as lithium, sodium, or potassium (e.g., sodium hydroxide, potassium hydroxide), carbonates of alkali metals such as lithium, sodium, potassium, or cesium (e.g., sodium carbonate, cesium carbonate), and organic bases such as triethylamine, sodium tert-butoxide, or potassium tert-butoxide. Suitable palladium catalysts include tetra(triphenylphosphine)palladium and [1,1'-bis(diphenylphosphine)ferrocene]palladium dichloride. In some cases, suitable ligands such as 1,1'-bis(diphenylphosphine)ferrocene, triphenylphosphine, and tritert-butylphosphine may be added.

[0034] Compounds of general formula I-1 react with suitable oxidants to yield the corresponding sulfoxides, i.e., compounds of general formula I-2. Suitable oxidants include m-chloroperoxybenzoic acid, hydrogen peroxide, or sodium (meta)periodate. Reaction solvents are mainly selected from water, methanol, ethanol, diethyl ether, dichloromethane, chloroform, carbon tetrachloride, hexane, benzene, toluene, ethyl acetate, DMF, tetrahydrofuran, or dioxane. The reaction is usually carried out at temperatures of 0-100°C, preferably 20-40°C. The reaction time is typically 10 minutes to 48 hours.

[0035] Because the compound of general formula I of this invention exhibits unexpectedly high acaricidal activity, the technical solution of this invention also includes the use of the compound of general formula I in agriculture or other fields for the preparation of acaricides. In particular, the compound of general formula I is active against important species of the following families (the listed objects are only used to illustrate the invention and are by no means limiting the invention): Tetranychidae (Tetranychus two-spotted, Tetranychus carmineus, Tetranychus maculata, Tetranychus citrus, Tetranychus kamizawa, Tetranychus hawthornus, etc.), Gallidae, Tardiidae, Aphididae, and Trichophytoncidae, etc.

[0036] Due to their positive properties, the above compounds can be advantageously used to protect important crops, livestock and breeding stock in agriculture and horticulture, as well as environments frequented by humans, from harmful mites.

[0037] To achieve the desired effect, the amount of compound used varies depending on various factors, such as the compound used, the crop being protected, the type of pest, the degree of infection, climatic conditions, the application method, and the formulation used.

[0038] A compound dosage of 10 grams to 5 kilograms per hectare can provide adequate control.

[0039] The present invention also includes an acaricidal composition having a compound of general formula I as the active ingredient. The acaricidal composition contains the active ingredient at a weight percentage between 0.1% and 99%. The acaricidal composition also includes an agriculturally, forestryly, and sanitarily acceptable carrier.

[0040] The compositions of the present invention can be applied in formulation form. Compounds of general formula I are dissolved or dispersed in a carrier or formulated as active ingredients for easier dispersion when used as acaricides. For example, these chemical formulations can be formulated as wettable powders, oil suspensions, aqueous suspensions, water emulsions, aqueous solutions, or emulsifiable concentrates. In these compositions, at least one liquid or solid carrier is added, and a suitable surfactant may be added if necessary.

[0041] The technical solution of the present invention also includes a method for controlling mites: applying the acaricidal composition of the present invention to the mites or their growth medium. A generally suitable effective amount is 10 to 1000 grams per hectare, preferably 20 to 500 grams per hectare.

[0042] For certain applications, such as in agriculture, one or more other fungicides, insecticides, acaricides, herbicides, plant growth regulators, or fertilizers may be added to the acaricide composition of the present invention, thereby producing additional advantages and effects.

[0043] It should be clearly stated that various modifications and alterations can be made within the scope defined by the claims of this invention. Detailed Implementation

[0044] The following specific embodiments are used to further illustrate the present invention, but the present invention is by no means limited to these examples. (Unless otherwise noted, all raw materials used are commercially available.) Example

[0045] Following the synthetic route described above, compounds of general formula I of this invention can be prepared by using different starting materials, as further described in detail below: Example 1: Preparation of (4-fluoro-5-iodo-2-methylphenyl)(2,2,2-trifluoroethyl) sulfide Step 1: N Preparation of 2-(fluoro-4-methylphenyl)-2,2,2-trifluoroacetamide

[0046] 2-fluoro-4-methylaniline (9.75 g, 78.00 mmol), triethylamine (12.04 g, 119.00 mmol), and dichloromethane (100 mL) were added to a 250 mL three-necked flask. After cooling to -10 °C in an ice-salt bath, trifluoroacetic anhydride (19.74 g, 94.00 mmol) was added dropwise. The reaction was continued for 2 h after the addition was complete. Most of the solvent was removed by vacuum distillation, and then water (300 mL) was added and stirred for 30 minutes. The mixture was filtered to obtain a white solid (15.33 g, 89%), which is the intermediate. N -(2-fluoro-4-methylphenyl)-2,2,2-trifluoroacetamide.

[0047] Step 2: Preparation of 4-fluoro-5-(2,2,2-trifluoroacetamido)-2-methylbenzenesulfonyl chloride

[0048] Add chlorosulfonic acid (43.11 g, 370.00 mmol) to a 100 mL three-necked flask, cool to -10 °C in an ice bath, and then slowly add the intermediate in batches. N -(2-fluoro-4-methylphenyl)-2,2,2-trifluoroacetamide (16.36 g, 74.00 mmol) was stirred at room temperature for 1 h and then slowly poured into ice water (200 mL) to quench the chlorosulfonic acid. The mixture was filtered, washed with water and dried to give a white solid (19.13 g, 81% yield), namely 4-fluoro-5-(2,2,2-trifluoroacetamido)-2-methylbenzenesulfonyl chloride.

[0049] Step 3: 2,2,2-trifluoro- N Preparation of 2-fluoro-5-mercapto-4-methylphenyl)acetamide

[0050] Intermediate 4-fluoro-5-(2,2,2-trifluoroacetamyl)-2-methylbenzenesulfonyl chloride (17.65 g, 55.22 mmol) and acetic acid (100 mL) were added to a 250 mL single-necked flask. Red phosphorus (2.90 g, 93.62 mmol) and iodine (0.28 g, 1.12 mmol) were added at room temperature, and the mixture was then heated to 120 °C. After 1 h, the mixture was cooled to 50 °C and filtered while hot. The filtrate was concentrated under vacuum. The residue was slowly poured into water (80 mL), extracted three times with ethyl acetate (150 mL each time), and concentrated under reduced pressure to obtain 2,2,2-trifluoro- N -(2-fluoro-5-mercapto-4-methylphenyl)acetamide (11.60 g, 72% yield) was used directly for the next step without further purification.

[0051] Step 4: Preparation of 5-amino-4-fluoro-2-methylbenzenethiol

[0052] Add an aqueous solution of sodium hydroxide (5.28 g / 40 mL, 132.00 mmol) to a 100 mL single-necked flask. Then add the intermediate 2,2,2-trifluoro- N 100-(2-fluoro-5-mercapto-4-methylphenyl)acetamide (9.62 g, 32.60 mmol), 100 o After reaction C for 1 h, the reaction solution was cooled to room temperature and the pH was adjusted to 7 with hydrochloric acid under ice bath conditions. The solution was then filtered and washed with water (50 mL) to obtain a grayish-white solid (3.12 g, 61%).

[0053] Step 5: Preparation of 2-fluoro-4-methyl-5-(2,2,2-trifluoroethyl)thio)aniline

[0054] Potassium carbonate (6.29 g, 45.50 mmol) and sodium formaldehyde sulfoxylate (2.36 g, 20.0 mmol) were added to a DMF (100 mL) solution of the intermediate 5-mercapto-2-fluoro-4-methylaniline (3.58 g, 22.75 mmol). Then, 2,2,2-trifluoroiodoethane (5.25 g, 25.02 mmol) was added dropwise over 1 hour in an ice-water bath. The resulting solution was stirred at room temperature for 8 hours. When the reaction was complete, water (200 mL) was added to the mixture, and the layers were extracted with ethyl acetate (150 mL × 3). The organic phase was dried over sodium sulfate, filtered, and concentrated under reduced pressure to give a yellow oil (4.04 g, 74% yield).

[0055] Step 6: Preparation of (4-fluoro-5-iodo-2-methylphenyl)(2,2,2-trifluoroethyl) sulfide

[0056] 10 g (41.80 mmol) of 2-fluoro-4-methyl-5-(2,2,2-trifluoroethyl)thio)aniline was added to a 500 mL three-necked flask along with 60 mL of concentrated hydrochloric acid. The mixture was stirred at 0–5 °C for 30 min. Then, 100 mL of an aqueous solution of sodium nitrite (3.46 g, 50.15 mmol) was added dropwise to the mixture and stirred for 1 h. Potassium iodide dissolved in 100 mL of water (13.88 g, 83.61 mmol) was then added dropwise to the reaction mixture, and the mixture was stirred at room temperature for 3 h at 0–5 °C. Ethyl acetate (300 mL) was added, followed by washing the organic phase with water (200 mL) and brine (200 mL), respectively. The mixture was dried over anhydrous MgSO4 and purified by rapid column chromatography to obtain a colorless oil (8.86 g, 60% yield).

[0057] Example 2: Preparation of (2-chloro-4-fluoro-5-iodophenyl)(2,2,2-trifluoroethyl) sulfide Step 1: N Preparation of -(4-chloro-2-fluorophenyl)-2,2,2-trifluoroacetamide

[0058] Refer to step 1 of Example 1 for intermediate N A method for synthesizing -(2-fluoro-4-methylphenyl)-2,2,2-trifluoroacetamide, using 4-chloro-2-fluoroaniline as a starting material to obtain an intermediate.N -(4-chloro-2-fluorophenyl)-2,2,2-trifluoroacetamide. White solid, yield 82%.

[0059] Step 2: Preparation of 2-chloro-4-fluoro-5-(2,2,2-trifluoroacetamido)benzenesulfonyl chloride

[0060] Referring to the synthesis method of intermediate 4-fluoro-5-(2,2,2-trifluoroacetamido)-2-methylbenzenesulfonyl chloride in step 2 of Example 1, the intermediate was used... N The intermediate 2-chloro-4-fluoro-5-(2,2,2-trifluoroacetamide)benzenesulfonyl chloride was prepared from 4-(4-chloro-2-fluorophenyl)-2,2,2-trifluoroacetamide. It was a white solid with a yield of 90%.

[0061] Step 3: N Preparation of -(4-chloro-2-fluoro-5-mercaptophenyl)-2,2,2-trifluoroacetamide

[0062] Referring to step 3 of Example 1, intermediate 2,2,2-trifluoro- N A method for synthesizing 2-(2-fluoro-5-mercapto-4-methylphenyl)acetamide, using the intermediate 2-chloro-4-fluoro-5-(2,2,2-trifluoroacetamido)benzenesulfonyl chloride as a starting material. N -(4-chloro-2-fluoro-5-mercaptophenyl)-2,2,2-trifluoroacetamide. White solid, 85% yield.

[0063] Step 4: Preparation of 5-amino-2-chloro-4-fluorobenzenethiol

[0064] Referring to the synthesis method of intermediate 5-amino-4-fluoro-2-methylbenzylthiol in step 4 of Example 1, the intermediate was used... N The intermediate 5-amino-2-chloro-4-fluorobenzylthiol was prepared from -(4-chloro-2-fluoro-5-mercaptophenyl)-2,2,2-trifluoroacetamide. It was a white solid with a yield of 51%.

[0065] Step 5: Preparation of 4-chloro-2-fluoro-5-(2,2,2-trifluoroethyl)thio)aniline

[0066] Following the method for synthesizing intermediate 2-fluoro-4-methyl-5-(2,2,2-trifluoroethyl)thio)aniline in step 5 of Example 1, intermediate 4-chloro-2-fluoro-5-(2,2,2-trifluoroethyl)thio)aniline was prepared from intermediate 5-amino-2-chloro-4-fluorobenzenethiol. The product was an oily substance with a yield of 76%.

[0067] Step 6: Preparation of (4-fluoro-5-iodo-2-chlorophenyl)(2,2,2-trifluoroethyl) sulfide

[0068] Following the method for synthesizing intermediate (4-fluoro-5-iodo-2-methylphenyl)(2,2,2-trifluoroethyl) sulfide in step 6 of Example 1, intermediate (4-fluoro-5-iodo-2-chlorophenyl)(2,2,2-trifluoroethyl) sulfide was prepared from intermediate 4-chloro-2-fluoro-5-(2,2,2-trifluoroethyl)thio)aniline. The product was an oily substance with a yield of 65%.

[0069] Example 3: Preparation of (4-fluoro-5-iodo-2-bromophenyl)(2,2,2-trifluoroethyl) sulfide Step 1: N Preparation of 4-bromo-2-fluorophenyl)-2,2,2-trifluoroacetamide

[0070] Refer to step 1 of Example 1 for intermediate N A method for synthesizing -(2-fluoro-4-methylphenyl)-2,2,2-trifluoroacetamide, using 4-bromo-2-fluoroaniline as a starting material to obtain an intermediate. N -(4-bromo-2-fluorophenyl)-2,2,2-trifluoroacetamide. White solid, yield 78%.

[0071] Step 2: Preparation of 2-bromo-4-fluoro-5-(2,2,2-trifluoroacetamido)benzenesulfonyl chloride

[0072] Referring to the synthesis method of intermediate 4-fluoro-5-(2,2,2-trifluoroacetamido)-2-methylbenzenesulfonyl chloride in step 2 of Example 1, the intermediate was used... N The intermediate 2-bromo-4-fluoro-5-(2,2,2-trifluoroacetamide)benzenesulfonyl chloride was prepared from 4-bromo-2-fluorophenyl)-2,2,2-trifluoroacetamide. It was a white solid with a yield of 91%.

[0073] Step 3: NPreparation of -(4-bromo-2-fluoro-5-mercaptophenyl)-2,2,2-trifluoroacetamide

[0074] Referring to step 3 of Example 1, intermediate 2,2,2-trifluoro- N A method for synthesizing 2-(2-fluoro-5-mercapto-4-methylphenyl)acetamide, using the intermediate 2-bromo-4-fluoro-5-(2,2,2-trifluoroacetamido)benzenesulfonyl chloride as a starting material. N -(4-bromo-2-fluoro-5-mercaptophenyl)-2,2,2-trifluoroacetamide. White solid, yield 81%.

[0075] Step 4: Preparation of 5-amino-2-bromo-4-fluorobenzenethiol

[0076] Referring to the synthesis method of intermediate 5-amino-4-fluoro-2-methylbenzylthiol in step 4 of Example 1, the intermediate was used... N The intermediate 5-amino-2-bromo-4-fluorobenzylthiol was prepared from 4-(4-bromo-2-fluoro-5-mercaptophenyl)-2,2,2-trifluoroacetamide. It was a white solid with a yield of 54%.

[0077] Step 5: Preparation of 4-bromo-2-fluoro-5-(2,2,2-trifluoroethyl)thio)aniline

[0078] Following the method for synthesizing intermediate 2-fluoro-4-methyl-5-(2,2,2-trifluoroethyl)thio)aniline in step 5 of Example 1, intermediate 4-bromo-2-fluoro-5-(2,2,2-trifluoroethyl)thio)aniline was prepared from intermediate 5-amino-2-bromo-4-fluorobenzenethiol. The product was an oily substance with a yield of 75%.

[0079] Step 6: Preparation of (4-fluoro-5-iodo-2-bromophenyl)(2,2,2-trifluoroethyl) sulfide

[0080] Following the method for synthesizing intermediate (4-fluoro-5-iodo-2-methylphenyl)(2,2,2-trifluoroethyl) sulfide in step 6 of Example 1, intermediate (4-fluoro-5-iodo-2-bromophenyl)(2,2,2-trifluoroethyl) sulfide was prepared from intermediate 4-bromo-2-fluoro-5-(2,2,2-trifluoroethyl)thio)aniline. The product was an oily substance with a yield of 55%.

[0081] Example 4: Preparation of 5-fluoro-4-iodo-2-(2,2,2-trifluoroethyl)thio)benzonitrile Step 1: Preparation of 4-amino-5-fluoro-2-(2,2,2-trifluoroethyl)thio)benzonitrile

[0082] Intermediate 4-bromo-2-fluoro-5-(2,2,2-trifluoroethyl)thio)aniline (1 g, 3.29 mmol) and cuprous cyanide (1.77 g, 19.74 mmol) were dissolved in 10 mL of DMF and stirred at 120 °C for 6 h. The suspension was filtered through a silica gel pad, and the filter cake was washed with ethyl acetate (20 mL). The filtrate was diluted with water (60 mL) and extracted with ethyl acetate (60 mL). The combined organic layers were concentrated under vacuum and column chromatography yielded 0.33 g of an oil, in 40% yield.

[0083] Step 2: Preparation of 5-fluoro-4-iodo-2-(2,2,2-trifluoroethyl)thio)benzonitrile

[0084] Following the synthesis method of intermediate (4-fluoro-5-iodo-2-methylphenyl)(2,2,2-trifluoroethyl) sulfide in step 6 of Example 1, intermediate 5-fluoro-4-iodo-2-(2,2,2-trifluoroethyl)thio)benzonitrile was prepared from intermediate 4-amino-5-fluoro-2-(2,2,2-trifluoroethyl)thio)benzonitrile. The product was an oily substance with a yield of 66%.

[0085] Example 5: Preparation of compound 1.1

[0086] (4-fluoro-5-iodo-2-chlorophenyl)(2,2,2-trifluoroethyl) sulfide (371 mg, 1 mmol, 1.0 eq), triphenylphosphine (25 mg, 0.1 mmol, 0.1 eq), palladium acetate (22 mg, 0.1 mmol, 0.1 eq), 4-chloro-phenylboronic acid (235 mg, 1.5 mmol, 1.5 eq), and potassium carbonate (424 mg, 3 mmol, 3.0 eq) were added to dioxane (5 mL), and after purging with nitrogen, the mixture was reacted at 80 °C for 4 hours. After the reaction was complete, water was added and the mixture was extracted three times with ethyl acetate. The combined organic phases were washed with water and saturated brine, dried over anhydrous sodium sulfate, filtered, and the concentrate was subjected to column chromatography to give the product (280 mg, 79%). 1 H NMR (600 MHz, Chloroform- d) δ 7.63 (d, 1H), 7.36 (s, 4H), 7.24 (d, 1H), 3.37 (q, 2H).

[0087] Example 6: Preparation of compound 1.2

[0088] Under ice bath conditions, m -CPBA (0.2 g, 1.01 mmol, 85% purity) was added in portions to a DCM (10 mL) solution of compound 1.1 (0.24 g, 0.67 mmol), and the mixture was stirred for 3 h. The reaction was monitored by TLC until complete. A saturated aqueous solution of sodium thiosulfate (15 mL) was added to separate the organic phase. The mixture was washed with 10% sodium carbonate solution and brine, dried over MgSO4, and concentrated under vacuum. Column chromatography yielded 0.2 g of a white solid (80% yield). 1 H NMR (600 MHz, Chloroform- d ) δ 7.97 (d,1H), 7.44 (dd, 2H), 7.42 – 7.36 (m, 2H), 7.26 (d, 1H), 3.70 (dq, 1H), 3.36(dq, 1H).

[0089] Example 7: Preparation of compound 2.1

[0090] Following the synthetic method of compound 1.1 in Example 5, compound 2.1 was prepared from (4-chlorophenyl)boric acid and the intermediate (4-fluoro-5-iodo-2-bromophenyl)(2,2,2-trifluoroethyl) sulfide. It was a white solid with a yield of 84%. The NMR data of compound 2.1 are as follows: 1 H NMR (600 MHz, Chloroform- d ) δ 7.70 (d, 1H), 7.48 (d, 1H), 7.43 (s, 4H), 3.45 (q, 2H).

[0091] Example 8: Preparation of compound 2.2

[0092] Compound 2.2 was prepared from compound 2.1 using the same synthetic method as compound 1.2 in Example 6. It was a white solid with a yield of 87%. The NMR data for compound 2.2 are as follows: 1 H NMR (600 MHz, Chloroform- d) δ 8.04 (d,1H), 7.55 – 7.41 (m, 5H), 3.80 (dq, 1H), 3.41 (dq, 1H).

[0093] Example 9: Preparation of compound 3.1

[0094] Following the synthetic method of compound 1.1 in Example 5, compound 3.1 was prepared from (4-chlorophenyl)boronic acid and the intermediate 5-fluoro-4-iodo-2-(2,2,2-trifluoroethyl)thio)benzonitrile. It was a white solid with a yield of 93%. The NMR data of compound 3.1 are as follows: 1 H NMR (600 MHz, Chloroform- d ) δ 7.78 (d, 1H), 7.52 (d, 1H), 7.48 (s, 4H), 3.54 (q, 2H).

[0095] Example 10: Preparation of compound 3.2

[0096] Following the synthesis method of compound 1.2 in Example 6, compound 3.2 was prepared from compound 3.1. It was a white solid with a yield of 78%. The NMR data of compound 3.2 are as follows: 1 H NMR (600 MHz, Chloroform- d ) δ 8.21 (d,1H), 7.63 (d, 1H), 7.58 – 7.54 (m, 2H), 7.51 (d, 2H), 3.73 (dq, 1H), 3.64(dq, 1H).

[0097] Example 11: Preparation of compound 4.1

[0098] Following the synthetic method of compound 1.1 in Example 5, compound 4.1 was prepared from (4-bromophenyl)boric acid and the intermediate (4-fluoro-5-iodo-2-chlorophenyl)(2,2,2-trifluoroethyl) sulfide. It was a white solid with a yield of 79%. The NMR data for compound 4.1 are as follows: 1 H NMR (600 MHz, Chloroform- d ) δ 7.69 (d, 1H), 7.59 (d, 2H), 7.37 (dd, 2H), 7.31 (d, 1H), 3.44 (q, 2H).

[0099] Example 12: Preparation of compound 4.2

[0100] Following the synthesis method of compound 1.2 in Example 6, compound 4.2 was prepared from compound 4.1. It was a white solid with a yield of 88%. The NMR data of compound 4.2 are as follows: 1 H NMR (600 MHz, Chloroform- d ) δ 8.04 (d,1H), 7.62 (d, 2H), 7.46 – 7.42 (m, 2H), 7.33 (d, 1H), 3.78 (dq, 1H), 3.43(dq, 1H).

[0101] Example 13: Preparation of compound 5.1

[0102] Following the synthetic method of compound 1.1 in Example 5, compound 5.1 was prepared from (4-bromophenyl)boric acid and the intermediate (4-fluoro-5-iodo-2-bromophenyl)(2,2,2-trifluoroethyl) sulfide. It was a white solid with a yield of 76%. The NMR data of compound 5.1 are as follows: 1 H NMR (600 MHz, Chloroform- d ) δ 7.70 (d, 1H), 7.62 – 7.55 (m, 2H), 7.48 (d, 1H), 7.40 – 7.34 (m, 2H), 3.45 (q, 2H).

[0103] Example 14: Preparation of compound 5.2

[0104] Following the synthesis method of compound 1.2 in Example 6, compound 5.2 was prepared from compound 5.1. It was a white solid with a yield of 96%. The NMR data of compound 5.2 are as follows: 1 H NMR (600 MHz, Chloroform- d ) δ 8.03 (d,1H), 7.61 (d, 2H), 7.49 (d, 1H), 7.45 (d, 2H), 3.80 (dq, 1H), 3.41 (dq, 1H).

[0105] Example 15: Preparation of compound 6.1

[0106] Following the synthetic method of compound 1.1 in Example 5, compound 6.1 was prepared from (4-bromophenyl)boronic acid and the intermediate 5-fluoro-4-iodo-2-(2,2,2-trifluoroethyl)thio)benzonitrile. It was a white solid with a yield of 84%. The NMR data of compound 6.1 are as follows: 1 H NMR (600 MHz, Chloroform- d ) δ 7.71 (d, 1H), 7.56 (d, 2H), 7.45 (d, 1H), 7.33 (dd, 2H), 3.46 (q, 2H).

[0107] Example 16: Preparation of compound 6.2

[0108] Following the synthetic method of compound 1.2 in Example 6, compound 6.2 was prepared from compound 6.1. It was a white solid with a yield of 94%. The NMR data of compound 6.2 are as follows: 1 H NMR (600 MHz, Chloroform- d ) δ 8.21 (d,1H), 7.67 (d, 2H), 7.63 (d, 1H), 7.49 (dd, 2H), 3.73 (dq, 1H), 3.64 (dq, 1H).

[0109] Example 17: Preparation of compound 7.1

[0110] Following the synthetic method of compound 1.1 in Example 5, compound 7.1 was prepared from (4-cyanophenyl)boric acid and the intermediate (4-fluoro-5-iodo-2-chlorophenyl)(2,2,2-trifluoroethyl) sulfide. It was a white solid with a yield of 76%. The NMR data for compound 7.1 are as follows: 1 H NMR (600 MHz, Chloroform- d ) δ 7.69 (d, 2H), 7.66 (d, 1H), 7.54 (dd, 2H), 7.29 (d, 1H), 3.38 (q, 2H).

[0111] Example 18: Preparation of compound 7.2

[0112] Following the synthetic method of compound 1.2 in Example 6, compound 7.2 was prepared from compound 7.1. It was a white solid with a yield of 89%. The NMR data of compound 7.2 are as follows: 1 H NMR (600 MHz, Chloroform- d ) δ 8.00 (d,1H), 7.71 (d, 2H), 7.62 (d, 2H), 7.31 (d, 1H), 3.72 (dq, 1H), 3.38 (dq, 1H).

[0113] Example 19: Preparation of compound 8.1

[0114] Following the synthetic method of compound 1.1 in Example 5, compound 8.1 was prepared from (4-cyanophenyl)boric acid and the intermediate (4-fluoro-5-iodo-2-bromophenyl)(2,2,2-trifluoroethyl) sulfide. It was a white solid with a yield of 76%. The NMR data for compound 8.1 are as follows: 1 H NMR (600 MHz, Chloroform- d ) δ 7.76 (d, 2H), 7.73 (d, 1H), 7.65 – 7.58 (m, 2H), 7.53 (d, 1H), 3.46 (q, 2H).

[0115] Example 20: Preparation of compound 8.2

[0116] Compound 8.2 was prepared from compound 8.1 using the same synthetic method as compound 1.2 in Example 6. It was a white solid with a yield of 78%. The NMR data for compound 8.2 are as follows: 1 H NMR (600 MHz, Chloroform- d ) δ 8.06 (d,1H), 7.82 – 7.76 (m, 2H), 7.70 (dd, 2H), 7.54 (d, 1H), 3.82 (dq, 1H), 3.42(dq, 1H).

[0117] Example 21: Preparation of compound 9.1

[0118] Following the synthetic method of compound 1.1 in Example 5, compound 9.1 was prepared from (4-cyanophenyl)boronic acid and the intermediate 5-fluoro-4-iodo-2-(2,2,2-trifluoroethyl)thio)benzonitrile. It was a white solid with a yield of 77%. The NMR data for compound 9.1 are as follows: 1 H NMR (600 MHz, Chloroform- d ) δ 7.85 – 7.77 (m, 3H), 7.67 –7.62 (m, 2H), 7.57 (d, 1H), 3.55 (q, 2H). Example 22: Preparation of compound 9.2

[0119] Following the synthetic method of compound 1.2 in Example 6, compound 9.2 was prepared from compound 9.1. It was a white solid with a yield of 85%. The NMR data of compound 9.2 are as follows: 1 H NMR (600 MHz, Chloroform- d ) δ 8.24 (d,1H), 7.83 (d, 2H), 7.74 (d, 2H), 7.69 (d, 1H), 3.83 – 3.71 (m, 1H), 3.70 –3.60 (m, 1H).

[0120] Bioactivity assay Example 23: Greenhouse acaricide activity determination The greenhouse acaricide activity was determined using the compound of general formula I obtained above, specifically: Based on the solubility of the compound to be tested, dissolve it in acetone or dimethyl sulfoxide, and prepare 50 mL of the required concentration of the test solution with 0.1% Tween 80 solution. The content of acetone or dimethyl sulfoxide in the solution shall not exceed 10%.

[0121] (1) Determination of the activity of adult Tetranychus cinnabarinus. Two true-leaf bean seedlings were inoculated with adult spider mites and their initial population was determined. The entire plant was then sprayed with a handheld sprayer. Each treatment was repeated three times. After treatment, the plants were placed in a standard observation room. The number of surviving mites was determined after 72 hours, and the mortality rate was calculated.

[0122] The test results are as follows: When the concentration of the drug solution is 1.25 mg / L, compounds 1.1, 1.2, 2.1, 2.2, 3.1, 3.2, 4.1, 4.2, 5.1, 5.2, 6.1, 6.2, 7.1, 7.2, 8.1, 8.2, 9.1, and 9.2 all have a mortality rate of no less than 90% against the red spider mite.

[0123] (2) Activity assay against Tetranychus cinnabarinus nymphs Take two true-leaf potted bean seedlings, then attach 10 healthy adult female spider mites to the leaves. Remove the adult mites after 24 hours and continue culturing the mite eggs. After 10 days, the nymphs are surveyed and then sprayed. Each treatment is repeated 3 times. After treatment, place the plants in a standard observation room and survey the number of surviving mites after 72 hours to calculate the mortality rate.

[0124] Following the above method, the compounds of the present invention and control compounds KC1~KC6 (synthesized in the same way as in Examples 1~22 of the present invention) were subjected to parallel determination of the activity of Tetranychus cinnabarinus. The test results are shown in Table 2.

[0125] Table 2. Data on the activity of killing Tetranychus cinnabarinus nymphs (mortality rate, %) .

[0126] Table 2 shows the comparative experimental data of the activity of compounds 1.1, 2.1, and 3.1 against the nymphs of *Tetranychus cinnabarinus*, compounds 1.2, 2.2, and 3.2 against the nymphs of *Tetranychus cinnabarinus*, compounds 4.1, 5.1, and 6.1 against the nymphs of *Tetranychus cinnabarinus*, compounds 4.2, 5.2, and 6.2 against the nymphs of *Tetranychus cinnabarinus*, compounds 7.1, 8.1, and 9.1 against the nymphs of *Tetranychus cinnabarinus*, and compounds 7.2, 8.2, and 9.2 against the nymphs of *Tetranychus cinnabarinus*. It can be seen that, through extensive experiments, the inventors of this invention, based on the existing molecular skeleton, significantly improved the acaricidal activity by replacing the methyl groups in the existing compound molecules with chlorine, bromine, or cyano groups, thus giving the compounds of this invention an unexpected effect compared to existing compounds.

[0127] (3) Assay for the activity of Tetranychus cinnabarinus eggs Take two potted bean seedlings with true leaves, remove one true leaf, and then attach 10 healthy adult female spider mites (Tetranychus carmineus) to the leaf. After 24 hours, remove the adult mites, count the number of eggs, and then spray the seedlings. Each treatment is repeated three times. Five days later, after all the eggs in the blank control have hatched, count the number of unhatched eggs in each treatment and calculate the hatching inhibition rate.

[0128] The test results are as follows: When the concentration of the drug solution was 2.5 mg / L, compounds 1.1, 1.2, 2.1, 2.2, 3.1, 3.2, 4.1, 4.2, 5.1, 5.2, 6.1, 6.2, 7.1, 7.2, 8.1, 8.2, 9.1, and 9.2 all inhibited the hatching of Tetranychus cinnabarinus eggs by no less than 90%.

Claims

1. A phenyl sulfide (sulfoxide) compound, characterized in that: The compound is shown in general formula I: ; In general formula I: R1 is selected from chlorine, bromine, or cyano groups; R3 is selected from chlorine, bromine, or cyano groups; R2 is selected from -CF3, -CHF2, -CH2F, -CH2CF3, -CH2CHF2, or -CH2CH2F; n is selected from 0 or 1.

2. The compound according to claim 1, characterized in that: In general formula I, R1 is selected from chlorine; R3 is selected from chlorine, bromine, or cyano groups; R2 is selected from -CF3, -CHF2, -CH2F, -CH2CF3, -CH2CHF2, or -CH2CH2F; n is selected from 0 or 1.

3. The compound according to claim 1, characterized in that: In general formula I, R1 is selected from bromine; R3 is selected from chlorine, bromine, or cyano groups; R2 is selected from -CF3, -CHF2, -CH2F, -CH2CF3, -CH2CHF2, or -CH2CH2F; n is selected from 0 or 1.

4. The compound according to claim 1, characterized in that: In general formula I, R1 is selected from cyano groups; R3 is selected from chlorine, bromine, or cyano groups; R2 is selected from -CF3, -CHF2, -CH2F, -CH2CF3, -CH2CHF2, or -CH2CH2F; n is selected from 0 or 1.

5. The compound according to claim 1, characterized in that, Compounds of general formula I are selected from the following specific compounds: 。 6. Use of a compound of general formula I according to any one of claims 1-5 as an acaricide in agriculture or forestry.

7. A mite-killing composition, characterized in that: The composition contains a compound of general formula I as described in any one of claims 1-5 and an agriculturally acceptable carrier, and the composition contains an active component in a weight percentage of 0.1-99%.

8. A method for controlling agricultural or forestry mites, characterized in that: Apply an effective amount of the composition of claim 7 to the mites or their growth medium that require control.

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