Phenyl sulfide (sulfoxide) compound and use thereof

Abstract

The present invention belongs to the field of agricultural acaricides. Specifically, the present invention relates to a phenyl sulfide (sulfoxide) compound and the use thereof. The compound has a structure as shown in general formula I, and each substituent group in the formula is as defined in the description. The compound of general formula I has good acaricidal activity and can be used for preventing and treating various pest mites.

Description

A phenyl sulfide (sulfoxide) compound and its application Technical Field

[0001] The present invention belongs to the field of agricultural acaricides, and in particular relates to a phenyl sulfide (sulfoxide) compound and application thereof. Background Art

[0002] Patent CN114957062A discloses the following compounds KC1 (Compound 3), KC2 (Compound 21), KC3 (Compound 4), KC4 (Compound 22), KC5 (Compound 1), and KC6 (Compound 19), which have good acaricidal activity:

[0003] In the prior art, there are no reports on the compounds represented by the general formula I of the present invention and their acaricidal activity. Moreover, compared with the prior art, the compounds of the present invention have higher acaricidal activity. Summary of the Invention

[0004] The object of the present invention is to provide a phenyl sulfide (sulfoxide) compound with better acaricidal effect, which can be used in the fields of agriculture, forestry and health to prevent and control pests and mites.

[0005] The technical solutions of the present invention are as follows:

[0006] A phenyl sulfide (sulfoxide) compound, as shown in the general formula I:

[0007] In the general formula I:

[0008] R1 is selected from chlorine, bromine or cyano;

[0009] R3 is selected from chlorine, bromine or cyano;

[0010] R2 is selected from -CF3, -CHF2, -CH2F, -CH2CF3, -CH2CHF2 or -CH2CH2F;

[0011] n is selected from 0 or 1.

[0012] In one possible implementation, in Formula I,

[0013] R1 is selected from chlorine;

[0014] R3 is selected from chlorine, bromine or cyano;

[0015] R2 is selected from -CF3, -CHF2, -CH2F, -CH2CF3, -CH2CHF2 or -CH2CH2F;

[0016] n is selected from 0 or 1.

[0017] In one possible implementation, in Formula I,

[0018] R1 is selected from bromine;

[0019] R3 is selected from chlorine, bromine or cyano;

[0020] R2 is selected from -CF3, -CHF2, -CH2F, -CH2CF3, -CH2CHF2 or -CH2CH2F;

[0021] n is selected from 0 or 1.

[0022] In one possible implementation, in Formula I,

[0023] R1 is selected from cyano;

[0024] R3 is selected from chlorine, bromine or cyano;

[0025] R2 is selected from -CF3, -CHF2, -CH2F, -CH2CF3, -CH2CHF2 or -CH2CH2F;

[0026] n is selected from 0 or 1.

[0027] In one possible implementation, the compound of formula I of the present invention is selected from the following specific compounds:

[0028] In the above technical solution, halogen refers to fluorine, chlorine, bromine or iodine.

[0029] Some of the compounds of general formula I of the present invention are shown below, but the present invention is by no means limited to these compounds.

[0030] Table 1

[0031] In the general formula I, when R1=Cl, R3=Cl, R2 is a different substituent and n is a different value as shown in Table 1, and the representative compounds are numbered 1.1-1.12.

[0032] In general formula I, when R1=Cl, R3=Br, R2 is a different substituent and n is a different value consistent with Table 1, and the representative compounds are numbered 2.1-2.12, corresponding to 1.1-1.12 in Table 1, respectively.

[0033] In general formula I, when R1=Cl, R3=CN, R2 is a different substituent and n is a different value consistent with Table 1, and the representative compounds are numbered 3.1-3.12, corresponding to 1.1-1.12 in Table 1, respectively.

[0034] In general formula I, when R1=Br, R3=Cl, R2 is a different substituent and n is a different value consistent with Table 1, and the representative compounds are numbered 4.1-4.12, corresponding to 1.1-1.12 in Table 1, respectively.

[0035] In general formula I, when R1=Br, R3=Br, R2 is a different substituent and n is a different value consistent with Table 1, and the representative compounds are numbered 5.1-5.12, corresponding to 1.1-1.12 in Table 1, respectively.

[0036] In general formula I, when R1=Br, R3=CN, R2 is a different substituent and n is a different value consistent with Table 1, and the representative compounds are numbered 6.1-6.12, corresponding to 1.1-1.12 in Table 1, respectively.

[0037] In general formula I, when R1=CN, R3=Cl, R2 is a different substituent and n is a different value consistent with Table 1, and the representative compounds are numbered 7.1-7.12, corresponding to 1.1-1.12 in Table 1, respectively.

[0038] In general formula I, when R1=CN, R3=Br, R2 is a different substituent and n is a different value consistent with Table 1, and the representative compounds are numbered 8.1-8.12, corresponding to 1.1-1.12 in Table 1, respectively.

[0039] In general formula I, when R1=CN, R3=CN, R2 is a different substituent and n is a different value consistent with Table 1, and the representative compounds are numbered 9.1-9.12, corresponding to 1.1-1.12 in Table 1, respectively.

[0040] The compounds of the general formula I of the present invention can be prepared according to the following schemes. Unless otherwise specified, the definitions of the groups in the formula are the same as above.

[0041] Using amino compound IX as the starting material, it reacts with trifluoroacetic anhydride under conventional conditions to obtain amino-protected amide compound VIII, which is further reacted with chlorosulfonic acid under heating conditions to obtain phenylsulfonyl chloride VII.

[0042] The sulfonyl chloride compound VII is reacted with a reducing agent to obtain the phenylthiophenol compound VI. The reaction is generally 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 generally 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 the compound of formula 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). An appropriate amount of an organic acid or inorganic acid such as formic acid, acetic acid, trifluoroacetic acid, hydrochloric acid, sulfuric acid or nitric acid may be added to the reaction; the molar ratio of the compound of formula VII to the 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).

[0043] Preferably, red phosphorus and iodine are further added in the reaction in this step.

[0044] Compound VI is hydrolyzed under conventional acidic or alkaline conditions to obtain intermediate aniline V.

[0045] The compound of formula IV can be prepared by reacting a compound of formula V with a halogenating agent or a sulfonate in a suitable solvent in the presence of a suitable base. The halogenating agent can be 2,2,2-trifluoroiodoethane, 2,2-difluoroiodoethane, or the like; the sulfonate can be 2,2,2-trifluoroethyl methanesulfonate, 2,2,2-trifluoroethyl benzenesulfonate, or 2,2,2-trifluoroethyl p-toluenesulfonate; and the molar ratio of the compound of 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, or 1:1-2). Suitable bases may be the same or different and include organic bases such as trimethylamine, triethylamine, pyridine, DBU, 4-dimethylaminopyridine, N,N-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, metal alkoxides such as sodium methoxide, sodium ethoxide, potassium ethoxide, potassium tert-butoxide, and sodium tert-butoxide; the molar ratio of the compound of formula VI to the 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, which may be the same or different, include 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; polar solvents such as water, acetonitrile, N,N-dimethylformamide, N-methylpyrrolidone, and dimethyl sulfoxide; or mixtures thereof. The reaction is typically carried out at a temperature between 0°C and the boiling point of the solvent. The reaction time is typically 0.5 and 48 hours.

[0046] The compound of formula IV is reacted with sodium nitrite, one or more acids, and potassium iodide to produce the compound of formula III. The acid can be an inorganic or organic acid, 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 typically carried out at a temperature of 0-100°C. The reaction time is typically 0.5-48 hours.

[0047] The compound of formula III is reacted with a substituted phenylboronic acid II in a suitable solvent, in the presence of a suitable base, and a suitable palladium catalyst at a temperature ranging from -10°C to the boiling point of the solvent for 0.5-48 hours to obtain a compound of formula I-1. Suitable solvents may be selected from water, dichloromethane, chloroform, carbon tetrachloride, hexane, benzene, toluene, acetonitrile, tetrahydrofuran, dioxane, DMF, or DMSO. Suitable bases include alkali metal hydrides such as lithium, sodium, or potassium, such as sodium hydride and potassium hydride; alkali metal hydroxides such as lithium, sodium, or potassium, such as sodium hydroxide and potassium hydroxide; alkali metal carbonates such as sodium carbonate and cesium carbonate; and organic bases such as triethylamine, sodium tert-butoxide, or potassium tert-butoxide. Suitable palladium catalysts may be selected from tetrakis(triphenylphosphine)palladium, [1,1'-bis(diphenylphosphino)ferrocene]dichloropalladium, and the like. In some cases, suitable ligands such as 1,1'-bis(diphenylphosphino)ferrocene, triphenylphosphine, tri-tert-butylphosphine, etc. may also be added.

[0048] The compound of formula I-1 reacts with a suitable oxidant to produce the corresponding sulfoxide, i.e., the compound of formula I-2. Suitable oxidants may be m-chloroperbenzoic acid, hydrogen peroxide, or sodium (meta)periodate. The reaction solvent is mainly selected from water, methanol, ethanol, ether, dichloromethane, chloroform, carbon tetrachloride, hexane, benzene, toluene, ethyl acetate, DMF, tetrahydrofuran, or dioxane. The reaction is usually carried out at a temperature of 0-100°C, preferably at 20-40°C. The reaction time is usually 10 minutes to 48 hours.

[0049] Because the compounds of Formula I of the present invention possess unexpectedly high acaricidal activity, the technical solutions of the present invention also include the use of the compounds of Formula I in the preparation of acaricides in agriculture or other fields. In particular, the compounds of Formula I are active against important species of the following families (this list is intended to illustrate the present invention only and is in no way limiting): Tetranychus urticae (Tetranychus cinnabarinus, Panonychus malus, Tetranychus citri, Tetranychus kanzawa, Tetranychus chinensis), Tetranychus serratus, Tetranychus chinensis, Tetranychus chinensis, Tetranychus chinensis, etc.), Tetranychus urticae, Tetranychus tarsi, Tetranychus serratus, Tetranychus serratus, etc.

[0050] Due to their positive properties, the above-mentioned compounds can be advantageously used for protecting important agricultural and horticultural crops, domestic and breeding stock, and environments frequented by humans from harmful mites.

[0051] To obtain the desired effect, the amount of compound used will vary depending on various factors, such as the compound used, the crop to be protected, the type of pest, the degree of infestation, climatic conditions, the method of application, the formulation used, etc.

[0052] Doses of 10 g to 5 kg of compound per hectare provide adequate control.

[0053] The present invention also includes an acaricidal composition comprising the compound of formula I as an active ingredient. The weight percentage of the active ingredient in the acaricidal composition is between 0.1% and 99%. The acaricidal composition also includes a carrier acceptable for agriculture, forestry, and hygiene.

[0054] The compositions of the present invention can be applied in the form of formulations. The compound of formula I, as the active ingredient, is dissolved or dispersed in a carrier or formulated into a formulation for easier dispersibility when used as a miticide. For example, these chemical formulations can be formulated as wettable powders, oil suspensions, aqueous suspensions, aqueous emulsions, aqueous solutions, or emulsifiable concentrates. These compositions contain at least one liquid or solid carrier and, if necessary, a suitable surfactant.

[0055] The technical solution of the present invention also includes a method for controlling pest mites: applying the acaricidal composition of the present invention to the pest mites or their growth medium. A generally suitable effective amount is 10 to 1000 grams per hectare, and preferably 20 to 500 grams per hectare.

[0056] 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 acaricidal composition of the present invention to produce additional advantages and effects.

[0057] It should be understood that various changes and modifications can be made within the scope of the present invention as defined by the claims. DETAILED DESCRIPTION

[0058] The following specific examples are used to further illustrate the present invention, but the present invention is in no way limited to these examples. (Unless otherwise noted, all raw materials used are commercially available)

[0059] Synthesis Example

[0060] According to the synthetic route described above, different raw materials can be used to prepare the compounds represented by the general formula I of the present invention, which are further described in detail as follows:

[0061] Example 1: Preparation of (4-fluoro-5-iodo-2-methylphenyl) (2,2,2-trifluoroethyl) sulfide

[0062] Step 1: Preparation of N-(2-fluoro-4-methylphenyl)-2,2,2-trifluoroacetamide

[0063] To a 250 mL three-necked flask, add the raw materials 2-fluoro-4-methylaniline (9.75 g, 78.00 mmol), triethylamine (12.04 g, 119.00 mmol), and dichloromethane (100 mL). Cool to -10°C in an ice-salt bath, then add trifluoroacetic anhydride (19.74 g, 94.00 mmol) dropwise. After the addition is complete, continue the reaction for 2 hours. Vacuum distillation to remove most of the solvent, then add water (300 mL) and stir for 30 minutes. Filter to obtain a white solid (15.33 g, 89%), the intermediate N-(2-fluoro-4-methylphenyl)-2,2,2-trifluoroacetamide.

[0064] Step 2: Preparation of 4-fluoro-5-(2,2,2-trifluoroacetamido)-2-methylbenzenesulfonyl chloride

[0065] Chlorosulfonic acid (43.11 g, 370.00 mmol) was added to a 100 mL three-necked flask. After cooling to -10°C in an ice bath, the intermediate N-(2-fluoro-4-methylphenyl)-2,2,2-trifluoroacetamide (16.36 g, 74.00 mmol) was slowly added in portions. The mixture was then stirred at room temperature for 1 hour and slowly poured into ice water (200 mL) to quench the chlorosulfonic acid. The mixture was filtered, washed with water, and dried to obtain a white solid (19.13 g, 81% yield), namely 4-fluoro-5-(2,2,2-trifluoroacetamido)-2-methylbenzenesulfonyl chloride.

[0066] Step 3: Preparation of 2,2,2-trifluoro-N-(2-fluoro-5-mercapto-4-methylphenyl)acetamide

[0067] To a 250 mL single-necked flask, the intermediate 4-fluoro-5-(2,2,2-trifluoroacetamido)-2-methylbenzenesulfonyl chloride (17.65 g, 55.22 mmol) and acetic acid (100 mL) were added. 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 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) and extracted with ethyl acetate three times, 150 mL each time. After concentration under reduced pressure, 2,2,2-trifluoro-N-(2-fluoro-5-mercapto-4-methylphenyl)acetamide (11.60 g, 72% yield) was obtained, which was used directly in the next step without further purification.

[0068] Step 4: Preparation of 5-amino-4-fluoro-2-methylbenzenethiol

[0069] A 100 mL single-necked flask was charged with aqueous sodium hydroxide solution (5.28 g / 40 mL, 132.00 mmol). The intermediate 2,2,2-trifluoro-N-(2-fluoro-5-mercapto-4-methylphenyl)acetamide (9.62 g, 32.60 mmol) was then added. The reaction was allowed to react at 100°C for 1 h. The reaction solution was cooled to room temperature and the pH was adjusted to 7 with hydrochloric acid in an ice bath. The solution was filtered and washed with water (50 mL) to obtain an off-white solid (3.12 g, 61%).

[0070] Step 5: Preparation of 2-fluoro-4-methyl-5-(2,2,2-trifluoroethyl)thio)aniline

[0071] To a solution of the intermediate 5-mercapto-2-fluoro-4-methylaniline (3.58 g, 22.75 mmol) in DMF (100 mL) were added potassium carbonate (6.29 g, 45.50 mmol) and sodium formaldehyde sulfoxylate (2.36 g, 20.0 mmol). 2,2,2-trifluoroiodoethane (5.25 g, 25.02 mmol) was then added dropwise under an ice-water bath over 1 h. The resulting solution was stirred at room temperature for 8 h. 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).

[0072] Step 6: Preparation of (4-fluoro-5-iodo-2-methylphenyl)(2,2,2-trifluoroethyl)sulfide

[0073] 2-Fluoro-4-methyl-5-(2,2,2-trifluoroethyl)thio)aniline (10 g, 41.80 mmol) and 60 mL of concentrated hydrochloric acid were added to a 500 mL three-necked flask. The mixture was stirred at 0-5°C for 30 min. A 100 mL aqueous solution of sodium nitrite (3.46 g, 50.15 mmol) was then added dropwise to the mixture, stirring for 1 h. Potassium iodide (13.88 g, 83.61 mmol) dissolved in 100 mL of water was then added dropwise to the reaction mixture, stirring at room temperature at 0-5°C for 3 h. Ethyl acetate (300 mL) was added, and the organic phase was washed with water (200 mL) and brine (200 mL), respectively, dried over anhydrous MgSO4, and purified by flash column chromatography to yield a colorless oil (8.86 g, 60% yield).

[0074] Example 2: Preparation of (2-chloro-4-fluoro-5-iodophenyl) (2,2,2-trifluoroethyl) sulfide

[0075] Step 1: Preparation of N-(4-chloro-2-fluorophenyl)-2,2,2-trifluoroacetamide

[0076] Referring to the synthesis method of the intermediate N-(2-fluoro-4-methylphenyl)-2,2,2-trifluoro-acetamide in Step 1 of Example 1, 4-chloro-2-fluoroaniline was used as the starting material to prepare the intermediate N-(4-chloro-2-fluorophenyl)-2,2,2-trifluoroacetamide. The product was a white solid in an 82% yield.

[0077] Step 2: Preparation of 2-chloro-4-fluoro-5-(2,2,2-trifluoroacetylamino)benzenesulfonyl chloride

[0078] Referring to the synthesis method of the intermediate 4-fluoro-5-(2,2,2-trifluoroacetamido)-2-methyl-benzenesulfonyl chloride in Step 2 of Example 1, the intermediate N-(4-chloro-2-fluorophenyl)-2,2,2-trifluoroacetamide was used as the starting material to prepare the intermediate 2-chloro-4-fluoro-5-(2,2,2-trifluoroacetamido)benzenesulfonyl chloride. The product was a white solid in a 90% yield.

[0079] Step 3: Preparation of N-(4-chloro-2-fluoro-5-mercaptophenyl)-2,2,2-trifluoroacetamide

[0080] Referring to the synthesis method of the intermediate 2,2,2-trifluoro-N-(2-fluoro-5-mercapto-4-methylphenyl)acetamide in Step 3 of Example 1, the intermediate N-(4-chloro-2-fluoro-5-mercaptophenyl)-2,2,2-trifluoroacetamide was prepared using the intermediate 2-chloro-4-fluoro-5-(2,2,2-trifluoroacetamido)benzenesulfonyl chloride as the starting material. The product was a white solid in an 85% yield.

[0081] Step 4: Preparation of 5-amino-2-chloro-4-fluorobenzenethiol

[0082] Referring to the synthesis method of the intermediate 5-amino-4-fluoro-2-methylbenzenethiol in Step 4 of Example 1, the intermediate N-(4-chloro-2-fluoro-5-mercaptophenyl)-2,2,2-trifluoroacetamide was used as the starting material to prepare the intermediate 5-amino-2-chloro-4-fluorobenzenethiol. The product was a white solid in a yield of 51%.

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

[0084] Referring to the synthesis method of the intermediate 2-fluoro-4-methyl-5-(2,2,2-trifluoroethyl)thio)aniline in Step 5 of Example 1, the intermediate 4-chloro-2-fluoro-5-(2,2,2-trifluoroethyl)thio)aniline was prepared using the intermediate 5-amino-2-chloro-4-fluorobenzenethiol as the starting material. The resulting product was an oil in a 76% yield.

[0085] Step 6: Preparation of (4-fluoro-5-iodo-2-chlorophenyl)(2,2,2-trifluoroethyl)sulfide

[0086] Referring to the synthesis method of the intermediate (4-fluoro-5-iodo-2-methylphenyl)(2,2,2-trifluoroethyl)sulfide in Step 6 of Example 1, the intermediate (4-fluoro-5-iodo-2-chlorophenyl)(2,2,2-trifluoroethyl)sulfide was prepared using the intermediate 4-chloro-2-fluoro-5-(2,2,2-trifluoroethyl)sulfanyl)aniline as the starting material. The resulting product was an oil in a 65% yield.

[0087] Example 3: Preparation of (4-fluoro-5-iodo-2-bromophenyl) (2,2,2-trifluoroethyl) sulfide

[0088] Step 1: Preparation of N-(4-bromo-2-fluorophenyl)-2,2,2-trifluoroacetamide

[0089] Referring to the synthesis method of the intermediate N-(2-fluoro-4-methylphenyl)-2,2,2-trifluoro-acetamide in Step 1 of Example 1, 4-bromo-2-fluoroaniline was used as the starting material to prepare the intermediate N-(4-bromo-2-fluorophenyl)-2,2,2-trifluoroacetamide. The product was a white solid in a yield of 78%.

[0090] Step 2: Preparation of 2-bromo-4-fluoro-5-(2,2,2-trifluoroacetylamino)benzenesulfonyl chloride

[0091] Referring to the synthesis method of the intermediate 4-fluoro-5-(2,2,2-trifluoroacetamido)-2-methyl-benzenesulfonyl chloride in Step 2 of Example 1, the intermediate N-(4-bromo-2-fluorophenyl)-2,2,2-trifluoroacetamide was used as the starting material to prepare the intermediate 2-bromo-4-fluoro-5-(2,2,2-trifluoroacetamido)benzenesulfonyl chloride. The product was a white solid in a 91% yield.

[0092] Step 3: Preparation of N-(4-bromo-2-fluoro-5-mercaptophenyl)-2,2,2-trifluoroacetamide

[0093] Referring to the synthesis method of the intermediate 2,2,2-trifluoro-N-(2-fluoro-5-mercapto-4-methylphenyl)acetamide in Step 3 of Example 1, the intermediate N-(4-bromo-2-fluoro-5-mercaptophenyl)-2,2,2-trifluoroacetamide was prepared using the intermediate 2-bromo-4-fluoro-5-(2,2,2-trifluoroacetamido)benzenesulfonyl chloride as the starting material. The product was a white solid in an 81% yield.

[0094] Step 4: Preparation of 5-amino-2-bromo-4-fluorobenzenethiol

[0095] Referring to the synthesis method of the intermediate 5-amino-4-fluoro-2-methylbenzenethiol in Step 4 of Example 1, the intermediate N-(4-bromo-2-fluoro-5-mercaptophenyl)-2,2,2-trifluoroacetamide was used as the starting material to prepare the intermediate 5-amino-2-bromo-4-fluorobenzenethiol. The product was a white solid in a yield of 54%.

[0096] Step 5: Preparation of 4-bromo-2-fluoro-5-(2,2,2-trifluoroethyl)thio)aniline

[0097] Referring to the synthesis method of the intermediate 2-fluoro-4-methyl-5-(2,2,2-trifluoroethyl)thio)aniline in Step 5 of Example 1, the intermediate 4-bromo-2-fluoro-5-(2,2,2-trifluoroethyl)thio)aniline was prepared using the intermediate 5-amino-2-bromo-4-fluorobenzenethiol as the starting material. The resulting product was an oil in a 75% yield.

[0098] Step 6: Preparation of (4-fluoro-5-iodo-2-bromophenyl)(2,2,2-trifluoroethyl)sulfide

[0099] Referring to the synthesis method of the intermediate (4-fluoro-5-iodo-2-methylphenyl)(2,2,2-trifluoroethyl)sulfide in Step 6 of Example 1, the intermediate (4-fluoro-5-iodo-2-bromophenyl)(2,2,2-trifluoroethyl)sulfide was prepared using the intermediate 4-bromo-2-fluoro-5-(2,2,2-trifluoroethyl)sulfanyl)aniline as the starting material. The resulting product was an oil in a 55% yield.

[0100] Example 4: Preparation of 5-fluoro-4-iodo-2-(2,2,2-trifluoroethyl)thio)benzonitrile

[0101] Step 1: Preparation of 4-amino-5-fluoro-2-(2,2,2-trifluoroethyl)thio)benzonitrile

[0102] The 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 in vacuo and purified by column chromatography to yield 0.33 g of an oil (40% yield).

[0103] Step 2: Preparation of 5-fluoro-4-iodo-2-(2,2,2-trifluoroethyl)thio)benzonitrile

[0104] Referring to the synthesis method of the intermediate (4-fluoro-5-iodo-2-methylphenyl)(2,2,2-trifluoroethyl)sulfide in Step 6 of Example 1, the intermediate 5-fluoro-4-iodo-2-(2,2,2-trifluoroethyl)sulfanylbenzonitrile was prepared using the intermediate 4-amino-5-fluoro-2-(2,2,2-trifluoroethyl)sulfanylbenzonitrile as the starting material. The resulting product was an oil in a 66% yield.

[0105] Example 5: Preparation of Compound 1.1

[0106] (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). After nitrogen displacement, the mixture was reacted at 80°C for 4 hours. After completion of the reaction, water was added and the mixture was extracted three times with ethyl acetate. The organic phases were combined, washed with water and saturated brine, dried over anhydrous sodium sulfate, filtered, and the concentrate was purified by column chromatography to obtain the product (280 mg, 79%). 1 H NMR (600MHz, Chloroform-d) δ7.63(d,1H),7.36(s,4H),7.24(d,1H),3.37(q,2H).

[0107] Example 6: Preparation of Compound 1.2

[0108] m-CPBA (0.2 g, 1.01 mmol, 85% purity) was added portionwise to a solution of compound 1.1 (0.24 g, 0.67 mmol) in DCM (10 mL) in an ice bath. The mixture was stirred for 3 h, and the reaction was monitored for completion by TLC. Saturated aqueous sodium thiosulfate (15 mL) was added, and the organic phase was separated, washed with 10% sodium carbonate solution and brine, dried over MgSO, and concentrated in vacuo. Column chromatography afforded 0.2 g of a white solid (80% yield). 1 H NMR (600MHz, Chloroform-d) δ7.97(d,1H),7.44(dd,2H),7.42-7.36(m,2H),7.26(d,1H),3.70(dq,1H),3.36(dq,1H).

[0109] Example 7: Preparation of Compound 2.1

[0110] Referring to the synthesis method of Compound 1.1 in Example 5, Compound 2.1 was prepared using (4-chlorophenyl)boronic acid and the intermediate (4-fluoro-5-iodo-2-bromophenyl)(2,2,2-trifluoroethyl)sulfide as raw materials. A white solid was obtained in an 84% yield. The NMR data of Compound 2.1 are as follows: 1 H NMR (600MHz, Chloroform-d) δ7.70(d,1H),7.48(d,1H),7.43(s,4H),3.45(q,2H).

[0111] Example 8: Preparation of Compound 2.2

[0112] Compound 2.2 was prepared by referring to the synthesis method of Compound 1.2 in Example 6 using Compound 2.1 as the starting material. A white solid was obtained in an 87% yield. The NMR data of Compound 2.2 are as follows: 1 H NMR (600MHz, Chloroform-d) δ8.04(d,1H),7.55-7.41(m,5H),3.80(dq,1H),3.41(dq,1H).

[0113] Example 9: Preparation of Compound 3.1

[0114] Referring to the synthesis method of Compound 1.1 in Example 5, Compound 3.1 was prepared using (4-chlorophenyl)boronic acid and the intermediate 5-fluoro-4-iodo-2-(2,2,2-trifluoroethyl)thio)benzonitrile as raw materials. A white solid was obtained in a 93% yield. The NMR data of Compound 3.1 are as follows: 1 H NMR (600MHz, Chloroform-d) δ7.78(d,1H),7.52(d,1H),7.48(s,4H),3.54(q,2H).

[0115] Example 10: Preparation of Compound 3.2

[0116] Compound 3.2 was prepared by referring to the synthesis method of Compound 1.2 in Example 6 using Compound 3.1 as the starting material. A white solid was obtained in a 78% yield. The NMR data of Compound 3.2 are as follows: 1 H NMR (600MHz, Chloroform-d) δ8.21(d,1H),7.63(d,1H),7.58-7.54(m,2H),7.51(d,2H),3.73(dq,1H),3.64(dq,1H).

[0117] Example 11: Preparation of Compound 4.1

[0118] Referring to the synthesis method of Compound 1.1 in Example 5, Compound 4.1 was prepared using (4-bromophenyl)boronic acid and the intermediate (4-fluoro-5-iodo-2-chlorophenyl)(2,2,2-trifluoroethyl)sulfide as raw materials. A white solid was obtained in a 79% yield. The NMR data of Compound 4.1 are as follows: 1 H NMR (600MHz, Chloroform-d) δ7.69(d,1H),7.59(d,2H),7.37(dd,2H),7.31(d,1H),3.44(q,2H).

[0119] Example 12: Preparation of Compound 4.2

[0120] Compound 4.2 was prepared by referring to the synthesis method of Compound 1.2 in Example 6 using Compound 4.1 as the starting material. A white solid was obtained in an 88% yield. The NMR data of Compound 4.2 are as follows: 1 H NMR (600MHz, Chloroform-d) δ8.04(d,1H),7.62(d,2H),7.46-7.42(m,2H),7.33(d,1H),3.78(dq,1H),3.43(dq,1H).

[0121] Example 13: Preparation of Compound 5.1

[0122] Referring to the synthesis method of Compound 1.1 in Example 5, Compound 5.1 was prepared using (4-bromophenyl)boronic acid and the intermediate (4-fluoro-5-iodo-2-bromophenyl)(2,2,2-trifluoroethyl)sulfide as raw materials. A white solid was obtained in a 76% yield. The NMR data of Compound 5.1 are as follows: 1 H NMR (600MHz, Chloroform-d) δ7.70(d,1H),7.62-7.55(m,2H),7.48(d,1H),7.40-7.34(m,2H),3.45(q,2H).

[0123] Example 14: Preparation of Compound 5.2

[0124] Compound 5.2 was prepared by referring to the synthesis method of Compound 1.2 in Example 6 using Compound 5.1 as the starting material. A white solid was obtained in a 96% yield. The NMR data of Compound 5.2 are as follows: 1H NMR (600MHz, Chloroform-d) δ8.03(d,1H),7.61(d,2H),7.49(d,1H),7.45(d,2H),3.80(dq,1H),3.41(dq,1H).

[0125] Example 15: Preparation of Compound 6.1

[0126] Referring to the synthesis method of Compound 1.1 in Example 5, Compound 6.1 was prepared using (4-bromophenyl)boronic acid and the intermediate 5-fluoro-4-iodo-2-(2,2,2-trifluoroethyl)thio)benzonitrile as raw materials. A white solid was obtained in an 84% yield. The NMR data of Compound 6.1 are as follows: 1 H NMR (600MHz, Chloroform-d) δ7.71(d,1H),7.56(d,2H),7.45(d,1H),7.33(dd,2H),3.46(q,2H).

[0127] Example 16: Preparation of Compound 6.2

[0128] Compound 6.2 was prepared by referring to the synthesis method of Compound 1.2 in Example 6 using Compound 6.1 as the starting material. A white solid was obtained in a 94% yield. The NMR data of Compound 6.2 are as follows: 1 H NMR (600MHz, Chloroform-d) δ8.21(d,1H),7.67(d,2H),7.63(d,1H),7.49(dd,2H),3.73(dq,1H),3.64(dq,1H).

[0129] Example 17: Preparation of Compound 7.1

[0130] Referring to the synthesis method of Compound 1.1 in Example 5, Compound 7.1 was prepared using (4-cyanophenyl)boronic acid and the intermediate (4-fluoro-5-iodo-2-chlorophenyl)(2,2,2-trifluoroethyl)sulfide as raw materials. A white solid was obtained in a 76% yield. The NMR data of Compound 7.1 are as follows: 1 H NMR (600MHz, Chloroform-d) δ7.69(d,2H),7.66(d,1H),7.54(dd,2H),7.29(d,1H),3.38(q,2H).

[0131] Example 18: Preparation of Compound 7.2

[0132] Compound 7.2 was prepared by referring to the synthesis method of Compound 1.2 in Example 6 using Compound 7.1 as the starting material. A white solid was obtained in an 89% yield. The NMR data of Compound 7.2 are as follows: 1 H NMR (600MHz, Chloroform-d) δ8.00(d,1H),7.71(d,2H),7.62(d,2H),7.31(d,1H),3.72(dq,1H),3.38(dq,1H).

[0133] Example 19: Preparation of Compound 8.1

[0134] Referring to the synthesis method of Compound 1.1 in Example 5, Compound 8.1 was prepared using (4-cyanophenyl)boronic acid and the intermediate (4-fluoro-5-iodo-2-bromophenyl)(2,2,2-trifluoroethyl)sulfide as raw materials. A white solid was obtained in a 76% yield. The NMR data of Compound 8.1 are as follows: 1 H NMR (600MHz, Chloroform-d) δ7.76(d,2H),7.73(d,1H),7.65-7.58(m,2H),7.53(d,1H),3.46(q,2H).

[0135] Example 20: Preparation of Compound 8.2

[0136] Compound 8.2 was prepared by referring to the synthesis method of Compound 1.2 in Example 6 using Compound 8.1 as the starting material. A white solid was obtained in a 78% yield. The NMR data of Compound 8.2 are as follows: 1 H NMR (600MHz, Chloroform-d) δ8.06(d,1H),7.82-7.76(m,2H),7.70(dd,2H),7.54(d,1H),3.82(dq,1H),3.42(dq,1H).

[0137] Example 21: Preparation of Compound 9.1

[0138] Referring to the synthesis method of Compound 1.1 in Example 5, Compound 9.1 was prepared using (4-cyanophenyl)boronic acid and the intermediate 5-fluoro-4-iodo-2-(2,2,2-trifluoroethyl)thio)benzonitrile as starting materials. A white solid was obtained in a 77% yield. The NMR data of Compound 9.1 are as follows: 1 H NMR (600MHz, Chloroform-d) δ7.85-7.77(m,3H),7.67-7.62(m,2H),7.57(d,1H),3.55(q,2H).

[0139] Example 22: Preparation of Compound 9.2

[0140] Compound 9.2 was prepared by referring to the synthesis method of Compound 1.2 in Example 6 using Compound 9.1 as the starting material. A white solid was obtained in an 85% yield. The NMR data of Compound 9.2 are as follows: 1 H NMR (600MHz, Chloroform-d) δ8.24(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).

[0141] Biological activity assay

[0142] Example 23: Determination of greenhouse acaricidal activity

[0143] The greenhouse mite-killing activity of the compound of formula I obtained above was determined, specifically:

[0144] According to the solubility of the test compound, dissolve it in acetone or dimethyl sulfoxide, and prepare 50 ml of the test solution of the required concentration with 0.1% Tween 80 solution. The content of acetone or dimethyl sulfoxide in the solution shall not exceed 10%.

[0145] (1) Determination of activity against adult Tetranychus cinnabarinus

[0146] Two true-leaf bean seedlings were inoculated with adult Tetranychus cinnabarinus mites and the base population was investigated. The entire plant was then sprayed with a handheld sprayer. Each treatment was repeated three times. After treatment, the seedlings were placed in a standard observation room. After 72 hours, the number of surviving mites was investigated and the mortality rate was calculated.

[0147] The test results are as follows:

[0148] When the concentration of the drug solution is 1.25 mg / L, the mortality rates of 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 to Tetranychus cinnabarinus are all not less than 90%.

[0149] (2) Determination of activity against Tetranychus cinnabarinus nymphs

[0150] Take two true leaf potted bean seedlings, then place 10 healthy female adult mites of Tetranychus cinnabarinus on the leaves. After 24 hours, remove the adult mites and continue to culture the mite eggs. After 10 days, investigate the base number of nymphs and then spray them. Repeat 3 times for each treatment. After treatment, place them in a standard observation room. After 72 hours, investigate the number of surviving mites and calculate the mortality rate.

[0151] According to the above method, the compounds of the present invention and reference compounds KC1-KC6 (synthesized by the same method as in Examples 1-22 of the present invention) were subjected to parallel assays for their activity against Tetranychus cinnabarinus. The test results are shown in Table 2.

[0152] Table 2 Data on the activity of killing nymphs of Tetranychus cinnabarinus (mortality rate, %)

[0153] From the comparative test data of the activity of compounds 1.1, 2.1, 3.1 and the control compound KC1 against cinnabarinus nymphs in Table 2, the comparative test data of the activity of compounds 1.2, 2.2, 3.2 and the control compound KC2 against cinnabarinus nymphs in Table 2, the comparative test data of the activity of compounds 4.1, 5.1, 6.1 and the control compound KC3 against cinnabarinus nymphs in Table 2, the comparative test data of the activity of compounds 4.2, 5.2, 6.2 and the control compound KC4 against cinnabarinus nymphs in Table 2, the comparative test data of the activity of compounds 7.1, 8.1, 9.1 and the control compound KC5 against cinnabarinus nymphs in Table 2, and the comparative test data of the activity of compounds 7.2, 8.2, 9.2 and the control compound KC6 against cinnabarinus nymphs in Table 2, it can be seen that: the inventors of the present invention have found through a large number of experiments that, based on the molecular skeleton of the existing compound, after replacing the methyl group in the existing compound molecule with chlorine, bromine or cyano, the acaricidal activity is greatly improved, thereby making the compounds of the present invention have unexpected effects compared with the existing compounds.

[0154] (3) Determination of activity against Tetranychus cinnabarinus eggs

[0155] Take two true-leaf potted bean seedlings, remove one true leaf, and then place 10 healthy female Tetranychus cinnabarinus mites onto the leaves. After 24 hours, remove the adult mites, count the eggs, and then spray the leaves. Repeat three times for each treatment. After five days, wait until all eggs in the blank control have hatched. Count the number of unhatched eggs in each treatment and calculate the hatching inhibition rate.

[0156] The test results are as follows:

[0157] When the drug concentration is 2.5 mg / L, the inhibition rates of 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 on the hatching of Tetranychus cinnabarinus eggs are not less than 90%.

Claims

1. A phenyl sulfide (sulfoxide) compound, characterized in that: The compound is shown in the general formula I: 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.

2. The compound according to claim 1, characterized in that: 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.

3. The compound according to claim 1, characterized in that: In the general formula I, R1 is selected from bromine; 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.

4. The compound according to claim 1, characterized in that: In the general formula I, R1 is selected from 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.

5. The compound according to claim 1, characterized in that The compound of general formula I is selected from the following specific compounds:

6. Use of a compound of general formula I according to any one of claims 1 to 5 as a miticide in agriculture or forestry.

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

8. A method for controlling agricultural or forestry pests, characterized by: An effective amount of the composition according to claim 7 is applied to the pest mites to be controlled or their growth medium.

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