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 the definition of each substituent group in the formula # imgabs0 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

Technical Field

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

[0002] Patent CN118164880A discloses the following compound KC1, which has a 100% lethality rate against adult Tetranychus cinnabarinus at 10 mg / L:

[0003]

[0004] In the prior art, the compounds shown in general formula I of the present invention and their acaricidal activities have not been reported. Moreover, compared with the prior art, the compounds of the present invention have higher acaricidal activities. Summary of the Invention

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

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

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

[0008]

[0009] In general formula I:

[0010] R1 is selected from halogen;

[0011] R2 is selected from -CF3, -CHF2, -CH2F, -CH2CF3, -CH2CHF2 or -CH2CH2F;

[0012] n is selected from 0 or 1.

[0013] In a possible implementation manner, in general formula I,

[0014] R1 is selected from chlorine or bromine;

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

[0016] n is selected from 0 or 1.

[0017] In addition, the present invention provides a method for preparing the above-mentioned phenyl sulfide (sulfoxide) compound, which includes the following steps:

[0018] Step 1): Subject compound VIII to a reduction reaction to obtain compound VII;

[0019] Step 2): Subject compound VII to a rearrangement reaction to obtain compound VI;

[0020] Step 3): Subject compound VI to a salt formation reaction to obtain the hydrochloride, hydrobromide, sulfate or fluoroborate compound of compound VI, i.e., the compound of general formula V;

[0021] Step 4): Subject the compound of general formula V to a Sandmeyer reaction to obtain the compound of general formula IV;

[0022] Step 5): Subject the compound of general formula IV to a sulfonation reaction to obtain the compound of general formula III;

[0023] Step 6): Subject the compound of general formula III to a reduction reaction to obtain the compound of general formula II;

[0024] Step 7): Subject the compound of general formula II to an alkylation reaction to obtain the compound of general formula I-1;

[0025] Step 8): Subject the compound of general formula I-1 to an oxidation reaction to obtain the compound of general formula I-2;

[0026]

[0027] Wherein:

[0028] R1 is selected from halogen;

[0029] R2 is selected from -CF3, -CHF2, -CH2F, -CH2CF3, -CH2CHF2 or -CH2CH2F;

[0030] X is selected from hydrogen or acetyl;

[0031] Y is selected from HCl, HBr, H2SO4 or HBF4.

[0032] In addition, the present invention provides an intermediate compound for preparing the above-mentioned phenyl sulfide (sulfoxide) compounds, and the intermediate compound is shown as general formula II:

[0033]

[0034] In general formula II:

[0035] R1 is selected from halogen;

[0036] X is selected from hydrogen or acetyl.

[0037] In addition, the present invention provides an intermediate compound for preparing the above-mentioned compound of general formula II, and the intermediate compound is shown as general formula III:

[0038]

[0039] In General Formula III:

[0040] R1 is selected from halogens.

[0041] In addition, the present invention provides a hydrochloride, hydrobromide, sulfate or fluoroborate compound of Compound VI, and the salt compound is as shown in General Formula V:

[0042]

[0043] In General Formula V:

[0044] Y is selected from HCl, HBr, H2SO4 or HBF4.

[0045] In addition, the present invention also provides the use of the compound of General Formula V for preparing the compound of General Formula I, the compound of General Formula II, the compound of General Formula III or the compound of General Formula IV.

[0046] In the above technical solution, the halogen refers to fluorine, chlorine, bromine or iodine.

[0047] Some compounds of General Formula I of the present invention are shown in Tables 1 to 4, but the present invention is by no means limited to these compounds.

[0048] Table 1

[0049]

[0050] In General Formula I, when R1 = Cl, R2 are different substituents and n are different values as shown in Table 1, and the representative compound numbers are 1.1 - 1.12.

[0051]

[0052] Table 2: In General Formula I, when R1 = F, R2 are different substituents and n are different values which are the same as those in Table 1, and the representative compound numbers are 2.1 - 2.12, corresponding to 1.1 - 1.12 in Table 1 in sequence.

[0053] Table 3: In General Formula I, when R1 = Br, R2 are different substituents and n are different values which are the same as those in Table 1, and the representative compound numbers are 3.1 - 3.12, corresponding to 1.1 - 1.12 in Table 1 in sequence.

[0054] Table 4: In General Formula I, when R1 = I, R2 are different substituents and n are different values which are the same as those in Table 1, and the representative compound numbers are 4.1 - 4.12, corresponding to 1.1 - 1.12 in Table 1 in sequence.

[0055] Some compounds of General Formula II of the present invention are shown in Table 7, but the present invention is by no means limited to these compounds.

[0056] Table 7

[0057]

[0058] Number <![CDATA[R1]]> X Number <![CDATA[R1]]> X 7.1 Cl H 7.2 Cl Acetyl 7.3 F H 7.4 F Acetyl 7.5 Br H 7.6 Br Acetyl 7.7 I H 7.8 I Acetyl

[0059] Some compounds of general formula III of the present invention are shown in Table 8, but the present invention is by no means limited to these compounds.

[0060] Table 8

[0061]

[0062] Number <![CDATA[R1]]> Number <![CDATA[R1]]> Number <![CDATA[R1]]> Number <![CDATA[R1]]> 8.1 Cl 8.2 F 8.3 Br 8.4 I

[0063] Some compounds of general formula V of the present invention are shown in Table 9, but the present invention is by no means limited to these compounds.

[0064] Table 9

[0065]

[0066] Number Y Number Y Number Y Number Y 9.1 HCl 9.2 HBr 9.3 <![CDATA[H2SO4]]> 9.4 <![CDATA[HBF4]]>

[0067] The compounds of general formula I (including compounds of general formula I-1 and general formula I-2), general formula II, general formula III and general formula V 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 before.

[0068]

[0069] Step 1): Preparation of the compound of general formula VII from the compound of general formula VIII

[0070] By a conventional method, the compound of general formula VII can be prepared by reacting the compound of general formula VIII in a suitable solvent, base and reducing agent at a temperature ranging from 40 °C to the boiling point of the solvent for 0.5 - 48 hours. Suitable bases include hydrides of alkali metals such as lithium, sodium or potassium, such as sodium hydride and potassium hydride, hydroxides of alkali metals such as lithium, sodium or potassium, such as sodium hydroxide and potassium hydroxide, and can also be carbonates of alkali metals lithium, sodium, potassium or cesium, such as sodium carbonate and cesium carbonate, or can also be organic bases such as triethylamine, sodium tert-butoxide or potassium tert-butoxide, etc. The reducing reagent can be red phosphorus, zinc, iron, copper, nickel or a mixture of red phosphorus, zinc, iron, copper and nickel in any proportion; the feeding molar ratio of the compound of general formula VIII to the reducing reagent is 1:1 - 30 (for example, 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), more preferably 1:1 - 20, further more preferably 1:1 - 10, for example, 1:3 - 6.

[0071] Step 2): Preparation of the general formula VI compound from the general formula VII compound

[0072] The general formula VI compound can be prepared by reacting the general formula VII compound under acidic conditions at a temperature ranging from -5°C to the boiling point of the solvent for 0.5 - 48 hours. 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.

[0073] Step 3): Preparation of the general formula V compound from the general formula VI compound

[0074] The general formula V compound can be prepared by reacting the general formula VI compound under acidic conditions at a temperature ranging from -5°C to the boiling point of the solvent for 0.5 - 48 hours. The acid can be hydrochloric acid, hydrobromic acid, sulfuric acid, or fluoroboric acid. The reaction solvent can be water, chloroform, dichloromethane, carbon tetrachloride, hexane, benzene, toluene, ethyl acetate, DMF, tetrahydrofuran, or dioxane, etc. Preferably, the molar ratio of the general formula VI compound to the acid added is 1:1 - 10, more preferably 1:2 - 8, and further preferably 1:2 - 6.

[0075] Step 4): Preparation of the general formula IV compound from the general formula V compound

[0076] The synthesis of the general formula IV compound can be achieved by carrying out a diazotization reaction on the general formula V compound under acidic conditions and then adding the corresponding CuX or potassium iodide. The fluoroborate is directly diazotized in the presence of fluoboric acid, and then the diazonium salt is decomposed by heating to obtain the general formula IV compound with R1 being fluorine. The temperature ranges from -10°C to the boiling point of the solvent. 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. Preferably, CuX is cuprous chloride or cuprous bromide. Preferably, the molar ratio of the general formula V compound to cuprous chloride, cuprous bromide, or potassium iodide added is 1:1 - 10, more preferably 1:2 - 8, and further preferably 1:2 - 6.

[0077] Step 5): Preparation of the general formula III compound from the general formula IV compound

[0078] The compound of general formula III can be prepared by reacting the compound of general formula IV with a sulfonating agent. The reaction is usually carried out at a temperature of 0 - 200 °C (such as 190 °C, 170 °C, 150 °C, 130 °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 sulfonating agent can be chlorosulfonic acid, fuming sulfuric acid, concentrated sulfuric acid, sulfur trioxide, sulfur monochloride, etc. The feeding molar ratio of the compound of general formula IV to the sulfonating agent is 1:1 - 100 (such as 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 - 8, 1:1 - 6, 1:1 - 4, 1:1 - 3, 1:1 - 2).

[0079] Step 6): Preparation of the compound of general formula II from the compound of general formula III

[0080] The compound of general formula II can be prepared by reacting the compound of general formula III with a reducing agent. The reaction is usually carried out at 0 - 150 °C (such as 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 proportion; the feeding molar ratio of the compound of general formula III to the reducing agent is 1:1 - 30 (such as 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). Appropriate amounts of organic acids or inorganic acids such as formic acid, acetic acid, trifluoroacetic acid, hydrochloric acid, sulfuric acid, or nitric acid can be added to the reaction; the feeding molar ratio of the compound of general formula III to the acid is 1:1 - 100 (such as 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).

[0081] Preferably, in the reaction of step 6), red phosphorus and iodine are further added.

[0082] Further preferably, the feeding molar ratio of the compound of general formula III to red phosphorus and iodine is 1:1 - 10:0.02 - 0.2, more preferably 1:2 - 8:0.05 - 0.15, and further preferably 1:2 - 6:0.05 - 0.1.

[0083] The thioacetyl group in the compound of general formula II can be subjected to conventional acidic hydrolysis or alkaline hydrolysis to obtain the compound of general formula II containing a mercapto group.

[0084] Step 7): Preparation of the compound of formula I-1 from the compound of formula II

[0085] The compound of formula I-1 can be prepared from the compound of formula II and a halogenating agent or a sulfonate ester in a suitable solvent in the presence of a suitable base. The halogenating agent can be trifluoroiodoethane, iodomethane, iodoethane, etc., and the sulfonate ester can be 2,2,2-trifluoroethyl methanesulfonate, 2,2,2-trifluoroethyl benzenesulfonate, 2,2,2-trifluoroethyl p-toluenesulfonate, etc.; the feeding molar ratio of the compound of formula II to the halogenating agent is 1:1-100 (for example, 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 organic bases such as trimethylamine, triethylamine, pyridine, DBU, 4-dimethylaminopyridine, N,N-diisopropylethylamine, etc., alkali metal hydrides such as sodium hydride, potassium hydride, etc., alkali metal hydroxides such as sodium hydroxide, potassium hydroxide, etc., alkaline earth metal hydroxides such as calcium hydroxide, etc., alkali metal carbonates such as sodium carbonate, potassium carbonate, etc., alkali metal bicarbonates such as sodium bicarbonate, etc., metal alkoxides such as sodium methoxide, sodium ethoxide, potassium ethoxide, potassium tert-butoxide, sodium tert-butoxide, etc.; the feeding molar ratio of the compound of formula II to the base is 1:1-20 (for example, 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 aromatic hydrocarbons such as benzene, toluene, xylene, etc., ketones such as acetone, methyl ethyl ketone, methyl isobutyl ketone, etc., halogenated hydrocarbons such as chloroform, dichloromethane, etc., esters such as methyl acetate, ethyl acetate, etc., ethers such as tetrahydrofuran, dioxane, diethyl ether, 1,2-dimethoxyethane, 1,4-dioxane, etc., polar solvents such as water, acetonitrile, N,N-dimethylformamide, N-methylpyrrolidone, dimethyl sulfoxide, etc. or a mixed solvent of the above 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.

[0086] Step 8): Preparation of the compound of formula I-2 from the compound of formula I-1

[0087] The compound of general formula I-1 can be reacted with an oxidizing reagent to obtain the compound of general formula I-2. The oxidizing reagent can be m-chloroperbenzoic acid, hydrogen peroxide or sodium (meta)periodate, etc. The reaction solvent can be water, methanol, ethanol, ether, dichloromethane, chloroform, 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, preferably at 0-30 °C. The reaction time is usually 10 minutes to 48 hours. Preferably, the feeding molar ratio of the compound of general formula I-1 to the oxidizing reagent is 1:1-10, more preferably 1:1-8, further more preferably 1:1-6, for example 1:1-5.

[0088] Due to the unexpectedly high acaricidal activity of the compound of general formula I of the present invention, the technical solution of the present invention also includes the use of the compound of general formula I as a preparation for acaricide drugs in agriculture or other fields. 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 present invention, but in no way limit the present invention): Tetranychidae (Tetranychus urticae, Tetranychus cinnabarinus, Panonychus ulmi, Panonychus citri, Tetranychus kanzawai, Tetranychus viennensis, etc.), Eriophyidae, Tarsonemidae, Podapolipodidae, Tenuipalpidae, etc.

[0089] Due to its positive properties, the above compounds can be advantageously used to protect important crops, livestock and breeding stock in agriculture and horticulture, as well as the environment frequented by humans from damage by pest mites.

[0090] To obtain the desired effect, the dosage of the compound varies due to various factors, such as the compound used, the crop to be pre-protected, the type of pest, the degree of infestation, climatic conditions, application method, dosage form adopted, etc.

[0091] A compound dosage of 10 grams to 5 kilograms per hectare can provide sufficient control.

[0092] The present invention also includes an acaricidal composition with the compound of general formula I as the active ingredient. The weight percentage content of the active ingredient in the acaricidal composition is between 0.1-99%. The acaricidal composition also includes carriers acceptable in agriculture, forestry and hygiene.

[0093] The composition of the present invention can be applied in the form of a preparation. The compound of general formula I is dissolved or dispersed in a carrier as an active ingredient or formulated into a preparation to be more easily dispersed when used as an acaricide. For example: these chemical preparations can be made into wettable powders, oil suspensions, water suspensions, emulsifiable concentrates, aqueous solutions or emulsifiable oils, etc. In these compositions, at least one liquid or solid carrier is added, and when necessary, a suitable surfactant can be added.

[0094] The technical solution of the present invention further includes a method for controlling harmful mites: applying the acaricidal composition of the present invention to the harmful mites or their growth medium. Generally, the more suitable effective amount selected is 10 grams to 1000 grams per hectare, and the preferred effective amount is 20 grams to 500 grams per hectare.

[0095] For certain applications, for example, in agriculture, one or more other fungicides, insecticidal acaricides, herbicides, plant growth regulators or fertilizers, etc. can be added to the acaricidal composition of the present invention, thereby additional advantages and effects can be produced.

[0096] It should be clear that various transformations and modifications can be made within the scope defined by the claims of the present invention. Detailed implementation mode

[0097] The following specific examples are used to further illustrate the present invention, but the present invention is by no means limited to these examples. (Unless otherwise specified, all raw materials used are commercially available)

[0098] Synthesis example

[0099] According to the synthesis route described above, by using different raw material compounds, the compounds shown in general formula I, general formula II, general formula III, and general formula V of the present invention can be respectively prepared and obtained, and are further specifically described as follows:

[0100] Example 1: Preparation of compound 1.1

[0101] (1) Preparation of intermediate 1,2-bis(3-fluorophenyl)hydrazine (VII)

[0102]

[0103] Add 819 g of 13% sodium hydroxide solution and m-fluoronitrobenzene (1050 g, 7.44 mol) to a 3 L three-necked flask, heat to 95 °C, and add 1858.5 g of zinc paste (978.2 g of zinc powder + 880.3 mL of water, 14.96 mol) in batches under stirring. During this period, keep the temperature at 95 °C - 105 °C, and finish adding in 3 h. Keep the temperature at 90 °C - 95 °C, and continue to add 912 g of zinc paste (480.7 g of zinc powder + 431.3 mL of water, 7.35 mol). After reacting for 6 h, monitor the reaction by TLC until it is complete. Stop the reaction, cool down to 3 - 7 °C, adjust the pH to 5 - 6 with 2.8 L of concentrated hydrochloric acid, filter under reduced pressure, wash the filter cake with water until neutral, dry it, add 800 mL of dichloromethane, stir at room temperature for 30 minutes, and then filter and dry to obtain 802.8 g of the intermediate, with a yield of 98.0%. 11H NMR (600 MHz, Chloroform-d) δ 7.22 - 7.11 (m, 2H), 6.75 - 6.45 (m, 6H), 5.71 (s, 2H). ESI-MS: m / z [M+H] + 221.22。

[0104] (2) Preparation of intermediate 2,2'-difluoro-[1,1'-biphenyl]-4,4'-diamine (VI)

[0105]

[0106] Concentrated hydrochloric acid (2173.8 mL, 26.08 mol) and 1445.5 mL of water were added to a 5 L three-necked flask, stirred at 0 °C, and intermediate VII (565.2 g, 2.57 mol) was added in portions within half an hour. After continuing to stir for 5 h, the reaction was transferred to room temperature (25 °C) and reacted for 3 h. The reaction was monitored by TLC until complete. The reaction solution was transferred to 0 °C, and the pH was adjusted to 10 - 11 with saturated sodium hydroxide. After suction filtration and drying, the obtained solid was recrystallized with 650 mL of toluene. After complete precipitation, suction filtration and drying gave 529.0 g of the intermediate, with a yield of 93.6%. 1 1H NMR (600 MHz, Chloroform-d) δ 7.13 - 7.10 (m, 2H), 6.50 - 6.43 (m, 4H), 3.79 (s, 4H).

[0107] (3) Preparation of intermediate 4,4'-dichloro-2,2'-difluoro-1,1'-biphenyl

[0108]

[0109] Intermediate VI (68.2 g, 0.31 mol) was added to a 250 mL three-necked flask and dissolved in 300 mL of ethyl acetate. Concentrated hydrochloric acid was added dropwise under stirring at room temperature until salification was complete. After suction filtration and drying, 9.1 of the hydrochloride was obtained. 1 1H NMR (600 MHz, DMSO-d6) δ 9.15 (s, 6H), 7.57 - 7.38 (m, 2H), 7.25 - 7.05 (m, 4H).

[0110] Add 312 mL of concentrated hydrochloric acid and 438 mL of water to a 1 L three-necked flask. Add the hydrochloride salt under stirring at room temperature. Transfer it to a -5 °C cold trap, and slowly add sodium nitrite (51.8 g, 0.75 mol) dropwise. The addition is completed in half an hour. Continue stirring for 2 h. Then, add the prepared diazonium salt dropwise to a 500 mL hydrochloric acid solution of copper(I) chloride (110.9 g, 1.12 mol). Keep the temperature between -10 and -5 °C and maintain vigorous stirring. The addition is completed in 3 h. After continuing to stir for 2 h, the reaction ends. Add 500 mL of ethyl acetate for extraction. The organic layer is extracted with water and saturated sodium chloride successively once, dried over anhydrous magnesium sulfate, and concentrated to obtain the crude product. Purify it by flash column chromatography to obtain 64.2 g of the intermediate 4,4'-dichloro-2,2'-difluoro-1,1'-biphenyl, with a yield of 80.1%. 1 HNMR (600 MHz, Chloroform-d) δ 7.31 - 7.28 (m, 2H), 7.23 (d, 2H), 7.22 - 7.19 (m, 2H).

[0111] (4) Preparation of intermediate 4,4'-dichloro-2',6-difluoro-[1,1'-biphenyl]-3-sulfonyl chloride (8.1)

[0112]

[0113] Add chlorosulfonic acid (3.2 g, 27.49 mmol) to DCM (6 mL). Add the intermediate 4,4'-dichloro-2,2'-difluoro-1,1'-biphenyl (3.6 g, 13.74 mmol) under stirring at room temperature. After the reaction is completed, add the reaction solution dropwise to water (200 mL) for quenching. The aqueous phase is extracted with DCM (200 mL). The organic layer is concentrated under vacuum to obtain a white solid (4.2 g, yield 85.5%), which is directly used for the next step without further purification.

[0114] (5) Preparation of intermediate 4,4'-dichloro-2',6-difluoro-[1,1'-biphenyl]-3-thiol (7.1)

[0115]

[0116] Add the intermediate 8.1 (5.6 g, 15.78 mmol), red phosphorus (0.8 g, 26.83 mmol), iodine (0.4 g, 1.58 mol), acetic anhydride (1.6 g, 15.78 mol), and acetic acid (50 mL) to the reaction flask in sequence. Heat to reflux for 4 h. After monitoring the reaction by TLC and it is completed, filter the reaction solution while it is hot. Concentrate the mother liquor, extract and separate layers with 200 mL of ethyl acetate and 200 mL of water. The organic layer is concentrated under reduced pressure to obtain 5.3 g of a white solid, which is the intermediate 7.2.

[0117] Add 5.3 g of white solid (Intermediate 7.2), 50 mL of tetrahydrofuran, and sodium formaldehyde sulfoxylate (1.9 g, 15.78 mmol) to a reaction flask, and cool it to 0 - 5 °C in an ice - water bath. Dropwise add an aqueous sodium hydroxide solution (2 g dissolved in 100 mL of water). During the dropping process, control the temperature at 0 - 5 °C. After the dropping is complete, continue stirring the reaction for 30 min. After monitoring the reaction by TLC until completion, add 100 mL of water and 100 mL of ethyl acetate to the reaction mixture, extract and separate the layers, and discard the organic phase. Dropwise add concentrated hydrochloric acid (4.4 g, 43.0 mmol) to the aqueous phase. After the dropping is complete, continue stirring for 30 min, and solid precipitates continuously. Add 200 mL of ethyl acetate for extraction. The organic phase is dried over anhydrous magnesium sulfate and concentrated under reduced pressure to obtain 3.8 g of white solid, which is Intermediate 7.1. The yield is 82.6%.

[0118] (6) Preparation of Compound 1.1

[0119]

[0120] Add Intermediate 7.1 (1.2 g, 3.99 mmol), 10 mL of DMF, potassium carbonate (1.10 g, 7.99 mmol), sodium formaldehyde sulfoxylate (0.2 g, 2.00 mmol), and 1 - iodotrifluoroethane (1.3 g, 5.99 mmol) to a reaction flask in sequence, and raise the temperature of the reaction solution to 40 °C and react for 5 h. After monitoring the reaction by TLC until completion, concentrate the reaction solution, and purify the residue by column chromatography to obtain 1.0 g of white solid, which is the target compound 1.1. The yield is 70.5%. 1 HNMR(600MHz,Chloroform - d)δ7.65(d,1H),7.33(d,1H),7.29(t,1H),7.27 - 7.20(m,2H),3.44(q,2H).

[0121] Example 2: Preparation of Compound 1.2

[0122]

[0123] Under ice - bath conditions, add m - CPBA (0.2 g, 1.01 mmol, purity 85%) in portions to a solution of Compound 1.1 (0.2 g, 0.66 mmol) in DCM (10 mL), stir for 3 h, and monitor the reaction by TLC until completion. Add a saturated aqueous sodium thiosulfate solution (15 mL), separate the organic phase, wash it with 10% sodium carbonate solution and brine, dry it with MgSO4, and concentrate it under vacuum. Column chromatography separation gives 0.2 g of white solid, which is Compound 1.2. The yield is 70.5%. 11H NMR (600 MHz, Chloroform-d) δ 7.99 (d, 1H), 7.34 (dd, 2H), 7.26 (ddd, 2H), 3.79 (dq, 1H), 3.44 (dq, 1H).

[0124] Example 3: Preparation of Compound 2.1

[0125] (1) Preparation of Intermediate 2,2',4,4'-Tetrafluoro-1,1'-biphenyl

[0126]

[0127] Add intermediate VI (6.9 g, 31.36 mmol) to a 250 mL three-necked flask, dissolve it in 60 mL of ethyl acetate, and dropwise add 40% fluoboric acid (41.3 g, 188.18 mmol) under stirring at room temperature. After stirring for 30 min after addition, filter with suction and dry to obtain 9.4 of the fluoborate. 1 1H NMR (600 MHz, DMSO-d6) δ 7.72 (s, 6H), 7.34 (t, 2H), 6.95 (d, 4H).

[0128] Add the fluoborate to 100 mL of 40% fluoboric acid, transfer it to a -5 °C cold trap, and then dropwise add sodium nitrite (5.2 g, 75.36 mmol). The addition is completed in half an hour. After continuing to stir for 2 h, filter the reaction solution with suction. The filter cake is the fluoboric acid diazonium salt; add the filter cake to a 250 mL single-necked flask, add 100 mL of toluene, and heat to reflux for 72 h. Stop the reaction, extract with 200 mL of ethyl acetate. The organic layer is extracted with water and saturated sodium chloride successively once, dried over anhydrous magnesium sulfate, concentrated to obtain the crude product, and purified by flash column chromatography to obtain 1.78 g, which is intermediate 2,2',4,4'-tetrafluoro-1,1'-biphenyl, with a yield of 25.1%. 1 1H NMR (600 MHz, DMSO-d6) δ 7.59 - 7.48 (m, 2H), 7.40 (s, 2H), 7.24 (t, 2H).

[0129] (2) Preparation of Intermediate 4'-Chloro-2',4,6-trifluoro-[1,1'-biphenyl]-3-sulfonyl chloride (8.2)

[0130]

[0131] Compound 8.2 can be prepared from intermediate 2,2',4,4'-tetrafluoro-1,1'-biphenyl according to the method described in step (4) of Example 1, with a yield of 98.5%.

[0132] (3) Preparation of Intermediate 2',4,4',6-Tetrafluoro-[1,1'-biphenyl]-3-thiol (7.3)

[0133]

[0134] According to the method described in step (5) of Example 1, intermediate 7.4 and intermediate 7.3 can be prepared from compound 8.2, with a yield of 82.5%.

[0135] (4) Preparation of compound 2.1

[0136]

[0137] According to the method described in step (6) of Example 1, compound 2.1 can be prepared from compound 7.3. 1 H NMR (600 MHz, Chloroform-d) δ 7.59 (t, 1H), 7.32 (td, 1H), 7.05 - 6.88 (m, 3H), 3.40 (q, 2H).

[0138] Example 4: Preparation of compound 2.2

[0139]

[0140] According to the method described in Example 2, compound 2.2 can be prepared from compound 2.1. 1 H NMR (600 MHz, Chloroform-d) δ 7.82 (t, 1H), 7.29 (td, 1H), 7.01 (t, 1H), 6.97 - 6.84 (m, 1H), 3.67 - 3.47 (m, 1H).

[0141] Example 5: Preparation of compound 3.1

[0142] (1) Preparation of intermediate 4,4'-dibromo-2,2'-difluoro-1,1'-biphenyl

[0143]

[0144] Add intermediate VI (6.9 g, 31.36 mmol) to a 250 mL three-necked flask, dissolve it in 60 mL of ethyl acetate, and dropwise add 40% hydrobromic acid (25.1 g, 125.45 mmol) under stirring at room temperature until the salt formation is complete. Filter with suction and wash with water to obtain the hydrobromide salt intermediate 9.2. 1 HNMR (600 MHz, DMSO-d6) δ 8.81 (s, 6H), 7.52 (dt, 2H), 7.33 - 7.18 (m, 4H).

[0145] The hydrobromide intermediate was added to 30 mL of hydrobromic acid and 40 mL of water, and the mixture was transferred to a -5 °C cold trap. Then, 30 mL of an aqueous solution of sodium nitrite (4.76 g, 68.99 mmol) was added dropwise. After the addition was complete, stirring was continued for 2 h. Then, the prepared diazonium salt was added dropwise to a 50 mL hydrobromic acid solution of cuprous bromide (9.0 g, 62.72 mmol) while maintaining the temperature between -10 and -5 °C and keeping vigorous stirring. The addition was completed in 3 h. After stirring for another 2 h, the reaction was terminated. 300 mL of ethyl acetate was added for extraction. The organic layer was successively extracted once with water and saturated sodium chloride, dried over anhydrous magnesium sulfate, and concentrated to obtain the crude product. After rapid column purification, 9.0 g of the product, namely intermediate 4,4'-dibromo-2,2'-difluoro-1,1'-biphenyl, was obtained with a yield of 82.5%. 1 H NMR (600 MHz, Chloroform-d) δ 7.39 - 7.33 (m, 4H), 7.25 - 7.20 (m, 2H).

[0146] (2) Preparation of compound 4,4'-dibromo-2',6-difluoro-[1,1'-biphenyl]-3-sulfonyl chloride (8.3)

[0147]

[0148] Compound 8.3 can be prepared from intermediate 4,4'-dibromo-2,2'-difluoro-1,1'-biphenyl according to the method described in step (4) of Example 1, with a yield of 93.5%.

[0149] (3) Preparation of intermediate 4,4'-dibromo-2',6-difluoro-[1,1'-biphenyl]-3-thiol (7.5)

[0150]

[0151] Intermediate 7.6 and intermediate 7.5 can be prepared from compound 8.3 according to the method described in step (5) of Example 1, with a yield of 85.6%.

[0152] (4) Preparation of compound 3.1

[0153]

[0154] Compound 3.1 can be prepared from compound 7.5 according to the method described in step (6) of Example 1. 1 H NMR (600 MHz, Chloroform-d) δ 7.67 - 7.63 (m, 1H), 7.49 (d, 1H), 7.41 - 7.35 (m, 2H), 7.25 - 7.20 (m, 1H), 3.53 - 3.36 (m, 2H).

[0155] Example 6: Preparation of Compound 3.2

[0156]

[0157] Compound 3.2 can be prepared from Compound 3.1 according to the method described in Example 2. 1 H NMR(600MHz,Chloroform-d)δ7.98(d,1H),7.50(d,1H),7.41(ddd,2H),7.29-7.26(m,1H),3.81(dq,1H),3.41(dq,1H).

[0158] Biological Activity Assay

[0159] Example 7: Activity Assay against Adult Tetranychus cinnabarinus

[0160] The acaricidal activity of the compounds of the present invention and the control compound KC1 was determined in a greenhouse. The determination method is as follows:

[0161] According to the solubility of the test compound, it was dissolved in acetone or dimethyl sulfoxide, and 50 ml of the test solution with the required concentration was prepared with a 0.1% Tween 80 solution. The content of acetone or dimethyl sulfoxide in the solution did not exceed 10%.

[0162] Two true leaf kidney bean seedlings were taken, inoculated with adult Tetranychus cinnabarinus and the base number was investigated, and then the whole plant was sprayed with a hand-held sprayer. Each treatment had 3 replicates. After treatment, it was placed in a standard observation room. After 72 hours, the number of surviving mites was investigated and the mortality rate was calculated.

[0163] The test results are as follows:

[0164] When the liquid medicine concentration was 10mg / L, the lethal rates of Compounds 1.1, 1.2, 2.1, 2.2, 3.1, 3.2 and the control compound KC1 against Tetranychus cinnabarinus were all 100%.

[0165] When the liquid medicine concentration was 1.25mg / L, the lethal rates of Compounds 1.1, 1.2, 2.1, 2.2, 3.1, 3.2 against Tetranychus cinnabarinus were all not less than 90%, while the lethal rate of the control compound KC1 against Tetranychus cinnabarinus was 0.

Claims

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

3. A method for preparing the phenyl sulfide (sulfoxide) compound according to any one of claims 1 or 2, which comprises the following steps: Step 1): Subject compound VIII to a reduction reaction to obtain compound VII; Step 2): Subject compound VII to a rearrangement reaction to obtain compound VI; Step 3): Subject compound VI to a salt formation reaction to obtain the hydrochloride, hydrobromide, sulfate or fluoroborate compound of compound VI, i.e., the compound of general formula V; Step 4): Subject the compound of general formula V to a Sandmeyer reaction to obtain the compound of general formula IV; Step 5): Subject the compound of general formula IV to a sulfonation reaction to obtain the compound of general formula III; Step 6): Subject the compound of general formula III to a reduction reaction to obtain the compound of general formula II; Step 7): Subject the compound of general formula II to an alkylation reaction to obtain the compound of general formula I-1; Step 8): Subject the compound of general formula I-1 to an oxidation reaction to obtain the compound of general formula I-2; Wherein: R1 is selected from halogens; R2 is selected from -CF3, -CHF2, -CH2F, -CH2CF3, -CH2CHF2 or -CH2CH2F; X is selected from hydrogen or acetyl; Y is selected from HCl, HBr, H2SO4 or HBF4.

4. A compound, which is an intermediate for preparing the phenyl sulfide (sulfoxide) compounds as described in any one of claims 1-2, characterized in that, The compound has the structure shown by the following general formula II: In general formula II: R1 is selected from halogens; X is selected from hydrogen or acetyl.

5. A compound, which is an intermediate for preparing the compound as claimed in claim 4, characterized in that, The compound has the structure shown by the following general formula III: In general formula III: R1 is selected from halogens.

6. A compound, characterized in that, The compound is the hydrochloride, hydrobromide, sulfate or fluoroborate compound of compound VI according to claim 3, and the salt compound has the structure shown by the following general formula V: In general formula V: Y is selected from HCl, HBr, H2SO4 or HBF4.

7. Use of the compound of general formula V according to claim 6 for preparing the compound of general formula I, the compound of general formula II, the compound of general formula III or the compound of general formula IV.

8. Use of the compound of general formula I according to claim 1 as a miticide in the field of agriculture or forestry.

9. A miticidal composition, characterized in that: The composition contains the compound of general formula I according to claim 1 and an agriculturally acceptable carrier, and the weight percentage content of the active ingredient in the composition is 0.1 - 99%.

10. A method for controlling agricultural or forestry pest mites, characterized in that: Apply an effective amount of the composition according to claim 9 to the mites to be controlled or their growth medium.

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