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 shown as a general formula I, wherein each substituent group in the formula is defined 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

TECHNICAL FIELD

[0001] The present application belongs to the field of agricultural acaricides, and particularly relates to a phenyl sulfide (sulfoxide) compound and application thereof. BACKGROUND

[0002] 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:

[0003]

[0004] The compound shown in the general formula I of the present application and the acaricidal activity thereof 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 present application aims to provide a phenyl sulfide (sulfoxide) compound with better acaricidal effect, which can be applied to the fields of agriculture, forestry and health for controlling pests and acarids.

[0006] The technical solution of the present application is as follows:

[0007] A phenyl sulfide (sulfoxide) compound, as shown in the general formula I:

[0008]

[0009] In the general formula I:

[0010] R1 is selected from chlorine, bromine or cyano;

[0011] R3 is selected from chlorine, bromine or cyano;

[0012] R2 is selected from -CF3, -CHF2, -CH2F, -CH2CF3, -CH2CHF2 or -CH2CH2F;

[0013] n is selected from 0 or 1.

[0014] In a possible implementation manner, in the general formula I,

[0015] R1 is selected from chlorine;

[0016] R3 is selected from chlorine, bromine or cyano;

[0017] R2 is selected from -CF3, -CHF2, -CH2F, -CH2CF3, -CH2CHF2 or -CH2CH2F;

[0018] n is selected from 0 or 1.

[0019] In one possible implementation form, in the general formula I,

[0020] R1is selected from bromine;

[0021] R3is selected from chlorine, bromine or cyano;

[0022] R2is selected from -CF3, -CHF2, -CH2F, -CH2CF3, -CH2CHF2or -CH2CH2F;

[0023] n is selected from 0 or 1.

[0024] In one possible implementation form, in the general formula I,

[0025] R1is selected from cyano;

[0026] R3is selected from chlorine, bromine or cyano;

[0027] R2is selected from -CF3, -CHF2, -CH2F, -CH2CF3, -CH2CHF2or -CH2CH2F;

[0028] n is selected from 0 or 1.

[0029] In one possible implementation form, the compound of general formula I according to the present application is selected from the following specific compounds:

[0030]

[0031]

[0032] In the above technical solution, halogen refers to fluorine, chlorine, bromine or iodine.

[0033] The compounds of general formula I according to the present application are shown below, but the present application is by no means limited to these compounds.

[0034] Table 1

[0035]

[0036] In the general formula I, when R1= Cl, R3= Cl, R2is different substituent and n is different value, see Table 1, the representative compound number is 1.1-1.12.

[0037] No. [R2] n No. [R2] n 1.1 - CF3 0 1.2 - CF3 1 1.3 -CHF2 0 1.4 -CHF2 1 1.5 -CH2F 0 1.6 -CH2F 1 1.7 -CH2CF3 0 1.8 <![CDATA[-CH2CF3]]> 1 1.9 -CH2CHF2 0 1.10 -CH2CHF2 1 1.11 -CH2CH2F 0 1.12 <![CDATA[-CH2CH2F]]> 1 .

[0038] In the general formula I, when R1= Cl, R3= Br, R2is different substituent and n is different value, which is consistent with Table 1, the representative compound number is 2.1-2.12, which corresponds to 1.1-1.12 of Table 1 in turn.

[0039] When R1= Cl, R3= CN, R2is different substituent and n is different number as same as Table 1 in general formula I, the compounds are numbered as 3.1-3.12, corresponding to 1.1-1.12 of Table 1 respectively.

[0040] When R1= Br, R3= Cl, R2is different substituent and n is different number as same as Table 1 in general formula I, the compounds are numbered as 4.1-4.12, corresponding to 1.1-1.12 of Table 1 respectively.

[0041] When R1= Br, R3= Br, R2is different substituent and n is different number as same as Table 1 in general formula I, the compounds are numbered as 5.1-5.12, corresponding to 1.1-1.12 of Table 1 respectively.

[0042] When R1= Br, R3= CN, R2is different substituent and n is different number as same as Table 1 in general formula I, the compounds are numbered as 6.1-6.12, corresponding to 1.1-1.12 of Table 1 respectively.

[0043] When R1= CN, R3= Cl, R2is different substituent and n is different number as same as Table 1 in general formula I, the compounds are numbered as 7.1-7.12, corresponding to 1.1-1.12 of Table 1 respectively.

[0044] When R1= CN, R3= Br, R2is different substituent and n is different number as same as Table 1 in general formula I, the compounds are numbered as 8.1-8.12, corresponding to 1.1-1.12 of Table 1 respectively.

[0045] When R1= CN, R3= CN, R2is different substituent and n is different number as same as Table 1 in general formula I, the compounds are numbered as 9.1-9.12, corresponding to 1.1-1.12 of Table 1 respectively.

[0046] The compounds of general formula I of the present application can be prepared according to the following scheme, wherein the definitions of the groups are the same as defined above, unless otherwise specified.

[0047]

[0048] The amino compound IX is used as starting material, reacted with trifluoroacetic anhydride under conventional conditions to obtain the amide compound VIII with amino protection, and further reacted with chlorosulfonic acid under heating to obtain the phenylsulfonyl chloride VII.

[0049] The sulfonyl chloride compound VII is reduced to give the phenyl sulfenol compound VI. The reaction is usually 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 usually 0.5-48 hours. The reducing agent can be red phosphorus, zinc, iron, copper, nickel or a mixture of red phosphorus, zinc, iron, copper, nickel in any ratio; the molar ratio of the compound of general 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). The reaction can be carried out in the presence of an appropriate amount of formic acid, acetic acid, trifluoroacetic acid, hydrochloric acid, sulfuric acid or nitric acid and the like organic or inorganic acids; the molar ratio of the compound of general 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).

[0050] Preferably, red phosphorus and iodine are further added in this step reaction.

[0051] The compound VI is hydrolyzed under acidic or basic conditions under conventional conditions to give the intermediate aniline V.

[0052] The compound of formula V can be reacted with a halogenating reagent or a sulfonic acid ester in the presence of a suitable base in a suitable solvent to produce the compound of formula IV. The halogenating reagent can be 2,2,2-trifluoroethyliodide, 2,2-difluoroethyliodide, etc. and the sulfonic acid ester can be 2,2,2-trifluoroethylmethanesulfonate, 2,2,2-trifluoroethylbenzenesulfonate, or 2,2,2-trifluorophenyl-p-toluenesulfonate, etc. The molar ratio of the compound of formula V to the halogenating reagent or the sulfonic acid ester 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). The suitable base can be the same or different and is an organic base such as trimethylamine, triethylamine, pyridine, DBU, 4-dimethylaminopyridine, N,N-diisopropylethylamine, etc., an alkali metal hydride such as sodium hydride, potassium hydride, etc., an alkali metal hydroxide such as sodium hydroxide, potassium hydroxide, etc., an alkaline earth metal hydroxide such as calcium hydroxide, etc., an alkali metal carbonate such as sodium carbonate, potassium carbonate, etc., an alkali metal bicarbonate such as sodium bicarbonate, etc., or a metal alkoxide such as sodium methoxide, sodium ethoxide, potassium ethoxide, potassium tert-butoxide, sodium tert-butoxide, etc. 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). The suitable solvent can be the same or different and is an aromatic hydrocarbon such as benzene, toluene, xylene, etc., a ketone such as acetone, methyl ethyl ketone, methyl isobutyl ketone, etc., a halogenated hydrocarbon such as chloroform, dichloromethane, etc., an ester such as methyl acetate, ethyl acetate, etc., an ether such as tetrahydrofuran, dioxane, diethyl ether, 1,2-dimethoxyethane, 1,4-dioxane, etc., a polar solvent such as water, acetonitrile, N,N-dimethylformamide, N-methylpyrrolidinone, dimethyl sulfoxide, etc., or a mixed solvent of the above-mentioned solvents. The reaction is usually carried out at 0°C to the boiling point of the solvent. The reaction time is usually 0.5-48 hours.

[0053] The compound of formula IV can be reacted with sodium nitrite, one or more acids, and potassium iodide to produce the compound of formula III. The acid can be an inorganic acid or an 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, etc. The reaction solvent can be water, chloroform, dichloromethane, carbon tetrachloride, hexane, benzene, toluene, ethyl acetate, DMF, tetrahydrofuran, or dioxane, etc. The reaction is usually carried out at a temperature of 0-100°C. The reaction time is usually 0.5-48 hours.

[0054] The compound of formula III is reacted with substituted phenylboronic acid II in a suitable solvent, in the presence of a suitable base, and a suitable palladium catalyst at a temperature from -10 °C to the boiling point of the solvent for 0.5 to 48 hours to give the compound of formula I-1. Suitable solvents can be selected from water, dichloromethane, chloroform, carbon tetrachloride, hexane, benzene, toluene, acetonitrile, tetrahydrofuran, dioxane, DMF or DMSO, etc. Suitable bases include alkali metal hydrides such as sodium hydride, potassium hydride, alkali metal hydroxides such as sodium hydroxide, potassium hydroxide, and alkali metal carbonates such as sodium carbonate, potassium carbonate, and organic bases such as triethylamine, sodium tert-butoxide, potassium tert-butoxide, etc. Suitable palladium catalysts can be selected from tetrakis(triphenylphosphine)palladium, [1,1'-bis(diphenylphosphino)ferrocene]dichloropalladium, etc. In some cases, a suitable ligand such as 1,1'-bis(diphenylphosphino)ferrocene, triphenylphosphine, tri-tert-butylphosphine, etc. can also be added.

[0055] The compound of formula I-1 is reacted with a suitable oxidizing agent to give the corresponding sulfoxide, i.e. the compound of formula I-2. Suitable oxidizing agents can be meta-chloroperoxybenzoic acid, hydrogen peroxide, or sodium (meta)periodate, etc. The reaction solvent is mainly selected from water, methanol, ethanol, diethyl ether, dichloromethane, chloroform, carbon tetrachloride, hexane, benzene, toluene, ethyl acetate, DMF, tetrahydrofuran, or dioxane, etc. The reaction is usually carried out at a temperature from 0 °C to 100 °C, preferably at 20 °C to 40 °C. The reaction time is usually from 10 minutes to 48 hours.

[0056] Since the compound of formula I has unexpectedly high acaricidal activity, the technical solution of the present application also includes the use of the compound of formula I in the preparation of acaricidal agents in the agricultural or other fields. In particular, the compound of formula I has activity on important species of the following families (the listed objects are only used to illustrate the present application, but by no means limit the present application): Tetranychidae (Tetranychus urticae, Tetranychus cinnabarinus, Panonychus mori, Panonychus citri, Tetranychus kanzawai, Panonychus pruni, etc.), Eriophyidae, Cheyletidae, Tyroglyphidae, and Tarsonemidae, etc.

[0057] Due to its positive properties, the above-mentioned compounds can be advantageously used for protecting important crops, domestic animals and breeding animals of the agricultural and horticultural sector, and the environment frequented by humans, from the damage caused by harmful mites.

[0058] To achieve the desired effect, the amount of the compound used varies depending on various factors, such as the compound used, the crop to be protected, the type of harmful organism, the degree of infestation, the climatic conditions, the method of application, the dosage form used, etc.

[0059] A dosage of 10 g to 5 kg of the compound per hectare can provide sufficient control.

[0060] The present application also includes acaricidal compositions comprising the compounds of Formula I as the active ingredient. The acaricidal compositions comprise the active ingredient in an amount of from 0.1 to 99% by weight. The acaricidal compositions further comprise an agriculturally, forestry, or hygienically acceptable carrier.

[0061] The compositions of the present application can be applied in the form of formulations. The compounds of Formula I are dissolved or dispersed in a carrier or formulated into formulations for easier dispersal when used as acaricides. For example, these formulations can be prepared as wettable powders, oil miscible liquids, suspensions, emulsifiable concentrates, water soluble concentrates, or emulsions. In these compositions, at least one liquid or solid carrier is added, and, if desired, suitable surfactants are added.

[0062] The technical solution of the present application also includes a method for controlling acarid pests by applying the acaricidal compositions of the present application to the acarid pests or their growth medium. The effective amount is usually selected to be from 10 to 1000 grams per hectare, and preferably from 20 to 500 grams per hectare.

[0063] For some applications, for example, in agriculture, one or more other fungicides, insecticides, acaricides, herbicides, plant growth regulators, or fertilizers can be added to the acaricidal compositions of the present application, thereby producing additional advantages and effects.

[0064] It should be understood that various modifications and changes can be made within the scope of the claims defined by the present application. DETAILED DESCRIPTION

[0065] The following specific examples are provided to further illustrate the present application, but the present application is in no way limited to these examples. (The raw materials used are commercially available unless otherwise noted)

[0066] Synthetic Examples

[0067] The compounds of Formula I of the present application can be prepared by following the synthetic routes described above using different starting compounds, and are further described in detail as follows:

[0068] Example 1: Preparation of (4-fluoro-5-iodo-2-methylphenyl)(2,2,2-trifluoroethyl)sulfide

[0069] Step 1: Preparation of N-(2-fluoro-4-methylphenyl)-2,2,2-trifluoroacetamide

[0070]

[0071] Into a 250 mL three-necked flask was placed starting material 2-fluoro-4- methyl aniline (9.75 g, 78.00 mmol), triethylamine (12.04 g, 119.00 mmol) and dichloromethane (100 mL). After cooling to -10 °C in an ice-salt bath, trifluoroacetic anhydride (19.74 g, 94.00 mmol) was added dropwise. The addition was completed and the reaction was continued for 2 h. Most of the solvent was removed by distillation under reduced pressure, then water (300 mL) was added and stirred for 30 min, and filtered to obtain white solid (15.33 g, 89%) which was intermediate N-(2-fluoro-4-methylphenyl)-2,2,2-trifluoroacetamide.

[0072] Step 2: Preparation of 4-fluoro-5-(2,2,2-trifluoroacetamido)-2-methylbenzenesulfonyl chloride

[0073]

[0074] Into a 100 mL three-necked flask was placed chlorosulfonic acid (43.11 g, 370.00 mmol), and cooled to -10 °C in an ice-salt bath. Intermediate N-(2-fluoro-4- methylphenyl)-2,2,2-trifluoroacetamide (16.36 g, 74.00 mmol) was added slowly in portions, then the mixture was stirred at room temperature for 1 h, and poured slowly into ice water (200 mL) to quench the chlorosulfonic acid. The mixture was filtered, washed with water and dried to obtain white solid (19.13 g, 81% yield) which was 4-fluoro-5-(2,2,2-trifluoroacetamido)-2-methylbenzenesulfonyl chloride.

[0075] Step 3: Preparation of 2,2,2-trifluoro-N-(2-fluoro-5-sulfhydryl-4-methylphenyl)acetamide

[0076]

[0077] Into a 250 mL single-necked flask was placed intermediate 4-fluoro-5-(2,2,2- trifluoroacetamido)-2-methylbenzenesulfonyl chloride (17.65 g, 55.22 mmol) and acetic acid (100 mL), and added red phosphorus (2.90 g, 93.62 mmol) and iodine (0.28 g, 1.12 mmol) at room temperature, then 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, 150 mL each time, a total of 3 times, and concentrated under reduced pressure to obtain 2,2,2-trifluoro-N-(2-fluoro-5-sulfhydryl-4-methylphenyl)acetamide (11.60 g, 72% yield) which was used directly in the next step without further purification.

[0078] Step 4: Preparation of 5-amino-4-fluoro-2-methylbenzenethiol

[0079]

[0080] Into a 100 mL single necked flask was added sodium hydroxide in water (5.28 g / 40 mL, 132.00 mmol). Then added intermediate 2,2,2-trifluoro-N-(2-fluoro-5-mercapto-4-methylphenyl)acetamide (9.62 g, 32.60 mmol), after 1 h at 100 °C, the reaction was cooled to room temperature, then adjusted to pH 7 with hydrochloric acid under ice bath condition, suction filtered and washed with water (50 mL) to give off-white solid (3.12 g, 61%).

[0081] Step 5: Preparation of 2-fluoro-4-methyl-5-(2,2,2-trifluoroethyl)thio)aniline

[0082]

[0083] Into a 100 mL single necked flask was added sodium hydroxide in water (5.28 g / 40 mL, 132.00 mmol). Then added intermediate 2,2,2-trifluoro-N-(2-fluoro-5-mercapto-4-methylphenyl)acetamide (9.62 g, 32.60 mmol), after 1 h at 100 °C, the reaction was cooled to room temperature, then adjusted to pH 7 with hydrochloric acid under ice bath condition, suction filtered and washed with water (50 mL) to give off-white solid (3.12 g, 61%).

[0084] Step 6: Preparation of (4-fluoro-5-iodo-2-methylphenyl)(2,2,2-trifluoroethyl) sulfide

[0085]

[0086] Into a 100 mL single necked flask was added sodium hydroxide in water (5.28 g / 40 mL, 132.00 mmol). Then added intermediate 2,2,2-trifluoro-N-(2-fluoro-5-mercapto-4-methylphenyl)acetamide (9.62 g, 32.60 mmol), after 1 h at 100 °C, the reaction was cooled to room temperature, then adjusted to pH 7 with hydrochloric acid under ice bath condition, suction filtered and washed with water (50 mL) to give off-white solid (3.12 g, 61%).

[0087] Example 2: Preparation of (2-chloro-4-fluoro-5-iodophenyl)(2,2,2- trifluoroethyl)sulfide

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

[0089]

[0090] The intermediate N-(4-chloro-2-fluorophenyl)-2,2,2-trifluoroacetamide was prepared according to the procedure described in Example 1, Step 1 for the synthesis of the intermediate N-(2-fluoro-4-methylphenyl)-2,2,2-trifluoroacetamide, using 4-chloro-2- fluorobenzenamine as starting material. White solid, yield 82%.

[0091] Step 2: Preparation of 2-chloro-4-fluoro-5-(2,2,2-trifluoroacetamido)benzenesulfonyl chloride

[0092]

[0093] The intermediate 2-chloro-4-fluoro-5-(2,2,2-trifluoroacetamido)benzenesulfonyl chloride was prepared according to the procedure described in Example 1, Step 2 for the synthesis of the intermediate 4-fluoro-5-(2,2,2-trifluoroacetamido)-2-methyl- benzenesulfonyl chloride, using the intermediate N-(4-chloro-2-fluorophenyl)-2,2,2- trifluoroacetamide as starting material. White solid, yield 90%.

[0094] Step 3: Preparation of N-(4-chloro-2-fluoro-5-mercaptophenyl)-2,2,2- trifluoroacetamide

[0095]

[0096] The intermediate N-(4-chloro-2-fluoro-5-mercaptophenyl)-2,2,2-trifluoroacetamide was prepared according to the procedure described in Example 1, Step 3 for the synthesis of the intermediate 2,2,2-trifluoro-N-(2-fluoro-5-mercapto-4-methylphenyl)acetamide, using the intermediate 2-chloro-4-fluoro-5-(2,2,2-trifluoroacetamido)benzenesulfonyl chloride as starting material. White solid, yield 85%.

[0097] Step 4: Preparation of 5-amino-2-chloro-4-fluorobenzene thiol

[0098]

[0099] The intermediate 5-amino-2-chloro-4-fluorobenzene thiol was prepared according to the procedure described in Example 1, Step 4 for the synthesis of the intermediate 5-amino-4-fluoro-2-methylbenzene thiol, using the intermediate N-(4-chloro-2-fluoro-5- mercaptophenyl)-2,2,2-trifluoroacetamide as starting material. White solid, yield 51%.

[0100] Step 5: Preparation of 4-chloro-2-fluoro-5-(2,2,2-trifluoroethyl)thio)aniline

[0101]

[0102] Intermediate 4-chloro-2-fluoro-5-(2,2,2-trifluoroethyl)thio)aniline was prepared according to the procedure described in Step 5 of Example 1 for the synthesis of intermediate 2-fluoro-4-methyl-5-(2,2,2-trifluoroethyl)thio)aniline using intermediate 5-amino-2-chloro-4-fluorobenzenethiol. Oil, 76% yield.

[0103] Step 6: Preparation of (4-fluoro-5-iodo-2-methylphenyl)(2,2,2- trifluoroethyl)sulfide

[0104]

[0105] Intermediate (4-fluoro-5-iodo-2-methylphenyl)(2,2,2-trifluoroethyl)sulfide was prepared according to the procedure described in Step 6 of Example 1 for the synthesis of intermediate (4-fluoro-5-iodo-2-methylphenyl)(2,2,2-trifluoroethyl)sulfide using intermediate 4-chloro-2-fluoro-5-(2,2,2-trifluoroethyl)thio)aniline. Oil, 65% yield.

[0106] Example 3: Preparation of (4-fluoro-5-iodo-2-bromophenyl)(2,2,2- trifluoroethyl)sulfide

[0107] Step 1: Preparation of N-(4-bromo-2-fluorophenyl)-2,2,2- trifluoroacetamide

[0108]

[0109] Intermediate N-(4-bromo-2-fluorophenyl)-2,2,2-trifluoroacetamide was prepared according to the procedure described in Step 1 of Example 1 for the synthesis of intermediate N-(2-fluoro-4-methylphenyl)-2,2,2-trifluoroacetamide using 4-bromo-2-fluoroaniline. White solid, 78% yield.

[0110] Step 2: Preparation of 2-bromo-4-fluoro-5-(2,2,2-trifluoroacetamido)benzenesulfonyl chloride

[0111]

[0112] Intermediate 2-bromo-4-fluoro-5-(2,2,2-trifluoroacetamido)benzenesulfonyl chloride was prepared from intermediate N-(4-bromo-2-fluorophenyl)-2,2,2- trifluoroacetamide following the procedure described in Step 2 of Example 1. White solid, 91% yield.

[0113] Step 3: Preparation of N-(4-bromo-2-fluoro-5-mercaptophenyl)-2,2,2- trifluoroacetamide

[0114]

[0115] Intermediate N-(4-bromo-2-fluoro-5-mercaptophenyl)-2,2,2-trifluoroacetamide was prepared from intermediate 2-bromo-4-fluoro-5-(2,2,2- trifluoroacetamido)benzenesulfonyl chloride following the procedure described in Step 3 of Example 1. White solid, 81% yield.

[0116] Step 4: Preparation of 5-amino-2-bromo-4-fluorobenzene thiol

[0117]

[0118] Intermediate 5-amino-2-bromo-4-fluorobenzene thiol was prepared from intermediate N-(4-bromo-2-fluoro-5-mercaptophenyl)-2,2,2-trifluoroacetamide following the procedure described in Step 4 of Example 1. White solid, 54% yield.

[0119] Step 5: Preparation of 4-bromo-2-fluoro-5-(2,2,2-trifluoroethyl)thio)aniline

[0120]

[0121] Intermediate 4-bromo-2-fluoro-5-(2,2,2-trifluoroethyl)thio)aniline was prepared from intermediate 5-amino-2-bromo-4-fluorobenzene thiol following the procedure described in Step 5 of Example 1. Oil, 75% yield.

[0122] Step 6: Preparation of (4-fluoro-5-iodo-2-bromophenyl)(2,2,2- trifluoroethyl) sulfide

[0123]

[0124] The intermediate (4-fluoro-5-iodo-2-methylphenyl)(2,2,2-trifluoroethyl)sulfide was prepared according to the procedure described in Example 1, Step 6, using the intermediate 4-bromo-2-fluoro-5-(2,2,2-trifluoroethyl)sulfanyl)aniline as starting material. Oil, yield 55%.

[0125] Example 4: Preparation of 5-fluoro-4-iodo-2-(2,2,2-trifluoroethyl)sulfanyl)benzonitrile

[0126] Step 1: Preparation of 4-amino-5-fluoro-2-(2,2,2-trifluoroethyl)sulfanyl)benzonitrile

[0127]

[0128] The intermediate 4-amino-5-fluoro-2-(2,2,2-trifluoroethyl)sulfanyl)benzonitrile was prepared according to the procedure described in Example 1, Step 6, using the intermediate 4-bromo-2-fluoro-5-(2,2,2-trifluoroethyl)sulfanyl)aniline as starting material. Oil, yield 66%.

[0129] Step 2: Preparation of 5-fluoro-4-iodo-2-(2,2,2-trifluoroethyl)sulfanyl)benzonitrile

[0130]

[0131] The intermediate 5-fluoro-4-iodo-2-(2,2,2-trifluoroethyl)sulfanyl)benzonitrile was prepared according to the procedure described in Example 1, Step 6, using the intermediate 4-amino-5-fluoro-2-(2,2,2-trifluoroethyl)sulfanyl)benzonitrile as starting material. Oil, yield 66%.

[0132] Example 5: Preparation of compound 1.1

[0133]

[0134] (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 nitrogen purging, the reaction was carried out at 80 °C for 4 h. After completion of the reaction, water was added and extracted with ethyl acetate three times. The organic phase was combined, washed with water, saturated brine, dried over anhydrous sodium sulfate, filtered and concentrated. The crude was purified by column chromatography to obtain 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).

[0135] Example 6: Preparation of compound 1.2

[0136]

[0137] m-CPBA (0.2 g, 1.01 mmol, 85% purity) was added portion wise to a solution of compound 1.1 (0.24 g, 0.67 mmol) in DCM (10 mL) under ice bath conditions and stirred for 3 h. The reaction was monitored by TLC. Saturated aqueous sodium thiosulfate solution (15 mL) was added and the organic phase was separated, washed with 10% sodium carbonate solution and brine, dried over MgS04and concentrated in vacuo. Column chromatography gave 0.2 g of white solid in 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).

[0138] Example 7: Preparation of compound 2.1

[0139]

[0140] Compound 2.1 was prepared according to the procedure described in Example 5 for the synthesis of compound 1.1 using (4-chlorophenyl)boronic acid and intermediate (4-fluoro-5-iodo-2-bromophenyl)(2,2,2-trifluoroethyl)sulfide as starting materials. White solid, 84% yield. The NMR data of compound 2.1 are as follows: 1H NMR (600 MHz, Chloroform-d) δ 7.70 (d, 1H), 7.48 (d, 1H), 7.43 (s, 4H), 3.45 (q, 2H).

[0141] Example 8: Preparation of compound 2.2

[0142]

[0143] Compound 2.2 was prepared according to the procedure described in Example 6 for the synthesis of compound 1.2, starting from compound 2.1. White solid, yield 87%. 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).

[0144] Example 9: Preparation of compound 3.1

[0145]

[0146] Compound 3.1 was prepared according to the procedure described in Example 5 for the synthesis of compound 1.1, starting from (4-chlorophenyl)boronic acid and intermediate 5-fluoro-4-iodo-2-(2,2,2-trifluoroethyl)thio)benzonitrile. White solid, yield 93%. NMR data for 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).

[0147] Example 10: Preparation of compound 3.2

[0148]

[0149] Compound 3.2 was prepared according to the procedure described in Example 6 for the synthesis of compound 1.2, starting from compound 3.1. White solid, yield 78%. NMR data for 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).

[0150] Example 11 : Preparation of compound 4.1

[0151]

[0152] Compound 4.1 was prepared according to the synthetic method of compound 1.1 of Reference Example 5, using (4-bromophenyl)boronic acid and intermediate (4-fluoro-5-iodo-2-chlorophenyl)(2,2,2-trifluoroethyl)sulfide as starting materials. White solid, yield 79%. NMR data of 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).

[0153] Example 12: Preparation of compound 4.2

[0154]

[0155] Compound 4.2 was prepared according to the synthetic method of compound 1.2 of Reference Example 6, using compound 4.1 as starting material. White solid, yield 88%. 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).

[0156] Example 13: Preparation of compound 5.1

[0157]

[0158] Compound 5.1 was prepared according to the synthetic method of compound 1.1 of Reference Example 5, using (4-bromophenyl)boronic acid and intermediate (4-fluoro-5-iodo-2-bromophenyl)(2,2,2-trifluoroethyl)sulfide as starting materials. White solid, yield 76%. 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).

[0159] Example 14: Preparation of compound 5.2

[0160]

[0161] Compound 5.2 was prepared according to the synthetic method of compound 1.2 of Reference Example 6, using compound 5.1 as starting material. White solid, yield 96%. NMR data of compound 5.2 are as follows: 1H 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).

[0162] Example 15: Preparation of compound 6.1

[0163]

[0164] Compound 6.1 was prepared according to the synthetic procedure of Example 5, compound 1.1, using (4-bromophenyl)boronic acid and intermediate 5-fluoro-4-iodo-2-(2,2,2- trifluoroethyl)thio)benzonitrile as starting materials. White solid, yield 84%. NMR data for compound 6.1 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).

[0165] Example 16: Preparation of compound 6.2

[0166]

[0167] Compound 6.2 was prepared according to the synthetic procedure of Example 6, compound 1.2, using compound 6.1 as starting material. White solid, yield 94%. NMR data for compound 6.2 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).

[0168] Example 17: Preparation of compound 7.1

[0169]

[0170] Compound 7.1 was prepared according to the synthetic procedure of Example 5, compound 1.1, using (4-cyanophenyl)boronic acid and intermediate (4-fluoro-5-iodo-2-chlorophenyl)(2,2,2- trifluoroethyl) sulfide as starting materials. White solid, yield 76%. NMR data for compound 7.1 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).

[0171] Example 18: Preparation of compound 7.2

[0172]

[0173] Compound 7.2 was prepared according to the synthetic procedure of Example 6, compound 1.2, using compound 7.1 as the starting material. White solid, yield 89%. NMR data for 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).

[0174] Example 19: Preparation of compound 8.1

[0175]

[0176] Compound 8.1 was prepared according to the synthetic procedure of Example 5, compound 1.1, using (4-cyanophenyl)boronic acid and intermediate (4-fluoro-5-iodo-2- bromophenyl)(2,2,2-trifluoroethyl)sulfide as the starting material. White solid, yield 76%. 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).

[0177] Example 20: Preparation of compound 8.2

[0178]

[0179] Compound 8.2 was prepared according to the synthetic procedure of Example 6, compound 1.2, using compound 8.1 as the starting material. White solid, yield 78%. 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).

[0180] Example 21: Preparation of compound 9.1

[0181]

[0182] Compound 9.1 was prepared according to the procedure described in Example 5 for the synthesis of compound 1.1, using (4-cyanophenyl)boronic acid and intermediate 5-fluoro-4-iodo-2-(2,2,2-trifluoroethyl)thio)benzonitrile as starting materials. White solid, yield 77%. 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).

[0183] Example 22: Preparation of compound 9.2

[0184]

[0185] Compound 9.2 was prepared according to the procedure described in Example 6 for the synthesis of compound 1.2, using compound 9.1 as starting material. White solid, yield 85%. NMR data for 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).

[0186] Bioassay

[0187] Example 23: Greenhouse acaricidal activity assay

[0188] The compounds of general formula I obtained above were used to perform a greenhouse acaricidal activity assay, in particular:

[0189] Depending on the solubility of the compound to be tested, it was dissolved in acetone or dimethyl sulfoxide and the desired concentration of the test solution was prepared in 50 ml of a 0.1% Tween 80 solution, the content of acetone or dimethyl sulfoxide in the solution not exceeding 10%.

[0190] (1) Activity assay on T. c. adults

[0191] Two whole bean seedlings were inoculated with T. c. adults and the basal number was investigated, after which the whole plants were treated with a hand-held sprayer, with 3 repetitions per treatment. After treatment, the plants were placed in a standard observation chamber and the number of surviving mites was investigated after 72 hours, calculating the mortality rate.

[0192] The results of the test are as follows:

[0193] The mortality rates of the 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, 9.2 to T. c. are not less than 90% when the concentration of the liquid medicine is 1.25 mg / L.

[0194] (2) Activity determination on T. c. nymphs

[0195] Two pieces of true leaf potted bean seedlings are taken, and then 10 healthy T. c. female adult mites are connected to the leaf blades. After 24 hours, the adult mites are removed, and the mite eggs are continuously cultured. After 10 days, the investigation base of the nymphs is entered, and then spraying treatment is performed. Each treatment is repeated 3 times. After the treatment, the seedlings are placed in a standard observation room. After 72 hours, the number of surviving mites is investigated, and the mortality rate is calculated.

[0196] According to the above method, the activity of the compounds of the present application and the control compounds KC1-KC6 (synthetic method same as the examples 1-22 of the present application) on T. c. nymphs is determined in parallel. The test results are shown in Table 2.

[0197] Table 2: Activity data of T. c. nymphs (mortality rate, %)

[0198]

[0199]

[0200]

[0201] From the activity comparison test data of the compounds 1.1, 2.1, 3.1 and the control compound KC1 on T. c. nymphs, the activity comparison test data of the compounds 1.2, 2.2, 3.2 and the control compound KC2 on T. c. nymphs, the activity comparison test data of the compounds 4.1, 5.1, 6.1 and the control compound KC3 on T. c. nymphs, the activity comparison test data of the compounds 4.2, 5.2, 6.2 and the control compound KC4 on T. c. nymphs, the activity comparison test data of the compounds 7.1, 8.1, 9.1 and the control compound KC5 on T. c. nymphs, and the activity comparison test data of the compounds 7.2, 8.2, 9.2 and the control compound KC6 on T. c. nymphs, it can be seen that the inventors of the present application greatly improve the miticidal activity by replacing the methyl in the existing compound molecule with chlorine, bromine, and cyanide on the basis of the existing compound molecular skeleton, thereby making the compounds of the present application have unexpected effects relative to the existing compounds.

[0202] (3) Activity determination on T. c. eggs

[0203] Two pieces of true leaf potted bean seedlings were taken, one true leaf was removed, then 10 healthy T. cinnabarinus female adult mites were introduced onto the leaf, after 24 hours the adult mites were removed, after investigation of the number of eggs, spraying treatment was carried out, every treatment was repeated 3 times. After 5 days when the eggs in the blank control hatched completely, the number of unhatched eggs in each treatment was investigated, and the hatching inhibition rate was calculated.

[0204] The test results are as follows:

[0205] When the concentration of the drug solution is 2.5 mg / L, the hatching inhibition rates of T. cinnabarinus eggs by 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 are all 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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