Biphenyl compound and application thereof

Abstract

The invention belongs to the field of agricultural acaricides. In particular to a biphenyl 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 in particular relates to a biphenyl compound and application thereof. Background Art

[0002] In recent years, due to the long-term use of existing acaricides, pest mites have developed serious resistance, making prevention and control work extremely difficult. Therefore, it is necessary to continuously develop more efficient acaricides with unique mechanisms of action.

[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 biphenyl compound with better acaricidal effect, which can be used to control harmful mites in agriculture or forestry.

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

[0006] A biphenyl compound, as shown in general formula I:

[0007]

[0008] In the general formula I:

[0009] R1 is selected from fluorine, chlorine, bromine or iodine;

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

[0011] m is selected from 0 or 1;

[0012] n is selected from 0 or 1.

[0013] In addition, the present invention provides a method for preparing the above-mentioned biphenyl compound, which comprises the following steps:

[0014] Step 1): subjecting compound VIII to a reduction reaction to obtain compound VII;

[0015] Step 2): subjecting compound VII to a rearrangement reaction to obtain compound VI;

[0016] Step 3): subjecting compound VI to a salt-forming reaction to obtain a hydrochloride, hydrobromide, sulfate or fluoroborate salt of compound VI, i.e., a compound of formula V;

[0017] Step 4): subjecting the compound of formula V to a Sandmeyer reaction to obtain a compound of formula IV;

[0018] Step 5): Subject the compound of General Formula IV to a sulfonation reaction to obtain the compound of General Formula III;

[0019] Step 6): Subject the compound of General Formula III to a reduction reaction to obtain the compound of General Formula II;

[0020] Step 7): Subject the compound of General Formula II to an alkylation reaction to obtain the compound of General Formula I-1;

[0021] Step 8): Subject the compound of General Formula I-1 to an oxidation reaction to obtain the compound of General Formula I-2;

[0022]

[0023] Wherein:

[0024] R1 is selected from chlorine or bromine;

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

[0026] m is selected from 0 or 1;

[0027] n is selected from 0 or 1;

[0028] X is selected from hydrogen or acetyl;

[0029] Y is selected from HCl, HBr, H2SO4 or HBF4.

[0030] In addition, the present invention provides an intermediate compound for preparing the above-mentioned biphenyl compounds, and the intermediate compound is shown as General Formula II:

[0031]

[0032] In General Formula II:

[0033] R1 is selected from chlorine or bromine;

[0034] X is selected from hydrogen or acetyl.

[0035] 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:

[0036]

[0037] In General Formula III:

[0038] R1 is selected from chlorine or bromine.

[0039] In addition, the present invention provides a hydrochloride, hydrobromide, sulfate or fluoroborate compound of Compound VI, and the salt compound is shown as General Formula V:

[0040]

[0041] In General Formula V:

[0042] Y is selected from HCl, HBr, H2SO4 or HBF4.

[0043] 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.

[0044] Some compounds of General Formula I of the present invention are shown below, but the present invention is by no means limited to these compounds.

[0045]

[0046] In General Formula I, when R1 = Br, R2 are different substituents and m, n are different values as shown in Table 1, and the representative compound numbers are 1.1 - 1.18.

[0047] Table 1

[0048] Number <![CDATA[R2]]> m n Number <![CDATA[R2]]> m n Number <![CDATA[R2]]> m n 1.1 <![CDATA[-CF3]]> 0 0 1.2 <![CDATA[-CF3]]> 0 1 1.3 <![CDATA[-CF3]]> 1 1 1.4 <![CDATA[-CHF2]]> 0 0 1.5 <![CDATA[-CHF2]]> 0 1 1.6 <![CDATA[-CHF2]]> 1 1 1.7 <![CDATA[-CH2F]]> 0 0 1.8 <![CDATA[-CH2F]]> 0 1 1.9 <![CDATA[-CH2F]]> 1 1 1.10 <![CDATA[-CH2CF3]]> 0 0 1.11 <![CDATA[-CH2CF3]]> 0 1 1.12 <![CDATA[-CH2CF3]]> 1 1 1.13 <![CDATA[-CH2CHF2]]> 0 0 1.14 <![CDATA[-CH2CHF2]]> 0 1 1.15 <![CDATA[-CH2CHF2]]> 1 1 1.16 <![CDATA[-CH2CH2F]]> 0 0 1.17 <![CDATA[-CH2CH2F]]> 0 1 1.18 <![CDATA[-CH2CH2F]]> 1 1 .

[0049] In General Formula I, when R1 = Cl, R2 are different substituents and n are different values consistent with Table 1, and the representative compound numbers are 2.1 - 2.18, corresponding to 1.1 - 1.18 of Table 1 in sequence.

[0050] In General Formula I, when R1 = F, R2 are different substituents and n are different values consistent with Table 1, and the representative compound numbers are 3.1 - 3.18, corresponding to 1.1 - 1.18 of Table 1 in sequence.

[0051] In General Formula I, when R1 = I, R2 are different substituents and n are different values consistent with Table 1, and the representative compound numbers are 4.1 - 4.18, corresponding to 1.1 - 1.18 of Table 1 in sequence.

[0052] Some compounds of General Formula II of the present invention are shown in Table 2, but the present invention is by no means limited to these compounds.

[0053]

[0054] Table 2

[0055] Number <![CDATA[R1]]> X Number <![CDATA[R1]]> X 5.1 Br H 5.2 Br Acetyl 5.3 Cl H 5.4 Cl Acetyl .

[0056] Some compounds of General Formula III of the present invention are shown in Table 3, but the present invention is by no means limited to these compounds.

[0057]

[0058] Table 3

[0059] Number <![CDATA[R1]]> Number <![CDATA[R1]]> 6.1 Br 6.2 Cl 。

[0060] Some general formula V compounds of the present invention are shown in Table 4, but the present invention is by no means limited to these compounds.

[0061]

[0062] Table 4

[0063] Number Y Number Y Number Y Number Y 7.1 HCl 7.2 HBr 7.3 <![CDATA[H2SO4]]> 7.4 <![CDATA[HBF4]]> 。

[0064] The general formula I compounds (including general formula I-1 compounds and general formula I-2 compounds), general formula II compounds, general formula III compounds and general formula V compounds 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.

[0065]

[0066] Step 1): Preparation of general formula VII compound from general formula VIII compound

[0067] By a conventional method, the general formula VII compound can be prepared by reacting compound 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, potassium hydride, hydroxides of alkali metals such as lithium, sodium or potassium, such as sodium hydroxide, potassium hydroxide, and can also be carbonates of alkali metals lithium, sodium, potassium or cesium, such as sodium carbonate, cesium carbonate, and 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 molar ratio of compound VIII to the reducing reagent for feeding 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.

[0068] Step 2): Preparation of general formula VI compound from general formula VII compound

[0069] The compound of general formula VI can be prepared by reacting the compound of general formula VII 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.

[0070] Step 3): Preparation of the compound of general formula V from the compound of general formula VI

[0071] The compound of general formula V can be prepared by reacting the compound of general formula VI 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 fluoboric acid. The reaction solvent can be water, chloroform, dichloromethane, carbon tetrachloride, hexane, benzene, toluene, ethyl acetate, DMF, tetrahydrofuran, or dioxane, etc. Preferably, the feeding molar ratio of the compound of general formula VI to the acid is 1:1 - 10, more preferably 1:2 - 8, and further preferably 1:2 - 6.

[0072] Step 4): Preparation of the compound of general formula IV from the compound of general formula V

[0073] The synthesis of the compound of general formula IV can be achieved by carrying out a diazotization reaction on the compound of general formula V 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 compound of general formula IV where R1 is 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 feeding molar ratio of the compound of general formula V to cuprous chloride, cuprous bromide, or potassium iodide is 1:1 - 10, more preferably 1:2 - 8, and further preferably 1:2 - 6.

[0074] Step 5): Preparation of the compound of general formula III from the compound of general formula IV

[0075] 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).

[0076] Step 6): Preparation of the compound of general formula II from the compound of general formula III

[0077] 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). 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).

[0078] Preferably, in the reaction of step 6), red phosphorus and iodine are further added.

[0079] 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.

[0080] 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.

[0081] Step 7): Preparation of Compound of General Formula I-1 from Compound of General Formula II

[0082] The compound of general formula I-1 can be prepared from the compound of general 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 general 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 and can be 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, alkali metal carbonates such as sodium carbonate, potassium carbonate, etc., alkali metal bicarbonates such as sodium bicarbonate, 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 general 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 and can be 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.

[0083] Step 8): Preparation of Compound of General Formula I-2 from Compound of General Formula I-1

[0084] The compound of general formula I-1 can react with an oxidizing agent to obtain the compound of general formula I-2. The oxidizing agent 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 agent is 1:1-10, more preferably 1:1-8, further more preferably 1:1-6, for example 1:1-5.

[0085] 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.

[0086] Due to its positive characteristics, the above compounds can be advantageously used to protect important crops, livestock and breeding stock in agriculture and horticulture, as well as the environment where humans often go from the damage of harmful mites.

[0087] To obtain an ideal 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 infection, climatic conditions, application method, dosage form adopted, etc.

[0088] A compound dosage of 10 grams to 5 kilograms per hectare can provide sufficient control.

[0089] 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.

[0090] 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 appropriate surfactants can be added when needed.

[0091] 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. The generally selected more suitable effective amount is 10 grams to 1000 grams per hectare, and the preferred effective amount is 20 grams to 500 grams per hectare.

[0092] For certain applications, for example, in agriculture, one or more other fungicides, insecticides and acaricides, herbicides, plant growth regulators or fertilizers, etc. can be added to the acaricidal composition of the present invention, and additional advantages and effects can thus be produced.

[0093] It should be clear that various transformations and modifications can be carried out within the scope defined by the claims of the present invention. Detailed implementation mode

[0094] 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, the raw materials used are all commercially available)

[0095] Synthesis example

[0096] According to the synthetic 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 the further specific description is as follows:

[0097] Example 1: Preparation of compound 1.1

[0098] (1) Preparation of intermediate 1,2-bis(3-fluorophenyl)hydrazine (VII)

[0099]

[0100] Add 819 g of 13% sodium hydroxide solution and m-fluoronitrobenzene (1050 g, 3.44 mol) to a 3 L three-necked flask, heat to 95 °C, and add 1854.5 g of zinc paste (974.18 g of zinc powder + 880.32 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 (480.69 g of zinc powder + 431.31 mL of water, 3.35 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 802.76 g of the intermediate, with a yield of 94.0%. 1HNMR(600MHz,Chloroform-d)δ3.22 - 3.11(m,2H),6.75 - 6.45(m,6H),5.71(s,2H). ESI-MS: m / z[M + H] + 221.22。

[0101] (2) Preparation of intermediate 2,2'-difluoro-[1,1'-biphenyl]-4,4'-diamine (VI)

[0102]

[0103] Concentrated hydrochloric acid (2173.8 mL, 26.08 mol) and water 1445.5 mL 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. Stirring was continued for 5 h and then the reaction was transferred to room temperature (25 °C) for 3 h. The reaction was monitored by TLC and found to be complete. The reaction solution was transferred to 0 °C, and the pH was adjusted to 10 - 11 with saturated sodium hydroxide. It was filtered and dried. The obtained solid was recrystallized with 650 mL of toluene. After complete precipitation, it was filtered and dried to obtain 525.0 g of the intermediate, with a yield of 93.6%. 1 H NMR(600MHz,Chloroform-d)δ3.13 - 3.10(m,2H),6.50 - 6.43(m,4H),3.79(s,4H).

[0104] (3) Preparation of intermediate 4,4'-dibromo-2,2'-difluoro-1,1'-biphenyl

[0105]

[0106] Intermediate VI (6.9 g, 3,136 mmol) was added to a 250 mL three-necked flask and dissolved in 60 mL of ethyl acetate. 40% hydrobromic acid (25.1 g, 125.45 mmol) was added dropwise under stirring at room temperature until salt formation was complete. It was filtered, washed with water to obtain 7.2 of the hydrobromate intermediate. 1 HNMR(600MHz,DMSO-d6)δ4.81(s,6H),3.52(dt,2H),3.33 - 3.18(m,4H).

[0107] 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. A 30 mL aqueous solution of sodium nitrite (4.8 g, 64.99 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 (5.0 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 ended. 300 mL of ethyl acetate was added for extraction. The organic layer was extracted with water and saturated sodium chloride successively, dried over anhydrous magnesium sulfate, concentrated to obtain a crude product, and purified by flash column chromatography to obtain 5.0 g with a yield of 82.5%, namely the intermediate 4,4'-dibromo-2,2'-difluoro-1,1'-biphenyl. 1 H NMR (600 MHz, Chloroform-d) δ 3.39 - 3.33 (m, 4H), 3.25 - 3.20 (m, 2H).

[0108] (4) Preparation of compound 4,4'-dibromo-6,6'-difluoro-[1,1'-biphenyl]-3,3'-disulfonyl dichloride (6.1)

[0109]

[0110] Chlorosulfonic acid (44.3 g, 0.38 mol) was added to the reaction flask and cooled to 0 - 5 °C with ice water. The intermediate 4,4'-dibromo-2,2'-difluoro-1,1'-biphenyl (3.0 g, 0.02 mol) was added, and during this process, the temperature of the reaction solution did not exceed 10 °C. The temperature was raised to 25 - 30 °C and the reaction was maintained for 3 h. After monitoring the reaction by TLC and completion, the reaction solution was slowly poured into crushed ice, and a solid precipitated. It was filtered; the filtrate was extracted with ethyl acetate and water. The organic layer was washed with saturated brine, dried over anhydrous magnesium sulfate, filtered, and concentrated under reduced pressure to obtain a pale yellow solid, which was combined with the filter cake, and after drying, 10.4 g of pale yellow solid was obtained, namely intermediate 6.1, with a yield of 95.5%.

[0111] (5) Preparation of intermediate 4-bromo-4'-chloro-6,6'-difluoro-[1,1'-biphenyl]-3,3'-dithiol (5.1)

[0112]

[0113] To the reaction flask, add intermediate 6.1 (4.1 g, 14.86 mmol), red phosphorus (2.8 g, 85.16 mmol), iodine (0.4 g, 1.49 mmol), acetic anhydride (3.0 g, 25.72 mmol) and acetic acid (50 mL) in sequence. Heat up to reflux and react for 2 h. After monitoring the reaction by TLC and completion, filter the reaction solution while it is hot, concentrate the mother liquor, extract and layer with 300 mL of ethyl acetate and 300 mL of water. The organic layer is concentrated under reduced pressure to obtain 3.4 g of white solid, namely intermediate 5.2;

[0114] To the reaction flask, add 3.4 g of intermediate 3.2, 60 mL of tetrahydrofuran, sodium formaldehyde sulfoxylate (1.7 g, 14.86 mmol), and cool in an ice-water bath to 0 - 5 °C. Dropwise add an aqueous sodium hydroxide solution (2 g dissolved in 100 mL of water), and control the temperature at 0 - 5 °C during the dropping process. After the dropping is complete, continue to stir and react for 30 min. After monitoring the reaction by TLC and completion, add 100 mL of water and 100 mL of ethyl acetate to the reaction mixture, extract and layer, 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 to stir 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 4.5 g of white solid, namely intermediate 5.1, with a yield of 81.8%.

[0115] (6) Preparation of compound 1.1

[0116]

[0117] To the reaction flask, add intermediate 5.1 (1.3 g, 3.20 mmol), 10 mL of DMF, potassium carbonate (1.3 g, 5.6 mmol), sodium formaldehyde sulfoxylate (0.4 g, 3.20 mmol), and 1,1,2-trifluoro-1-iodoethane (1.3 g, 6.41 mmol) in sequence. Heat the reaction solution to 50 °C and react for 5 h. After monitoring the reaction by TLC and completion, concentrate the reaction solution, and purify the residue by column chromatography to obtain 1.3 g of white solid, namely the target compound 1.1, with a yield of 71.2%. 1 H NMR (600 MHz, Chloroform-d) δ 3.76 - 3.56 (m, 2H), 3.55 - 3.44 (m, 2H), 3.45 (q, 4H).

[0118] Example 2: Preparation of compounds 1.2 and 1.3

[0119]

[0120] Under ice bath conditions, m-CPBA (0.2 g, 1.01 mmol, purity 85%) was added portionwise to a solution of 1.1 (0.3 g, 0.66 mmol) in DCM (20 mL). The mixture was stirred for 3 h and monitored by TLC until the reaction was complete. 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 MgSO4, concentrated in vacuo, and the residue was purified by column chromatography to give 0.09 g of compound 1.2 in a yield of 30.3% and 0.13 g of compound 1.3 in a yield of 41.5%. The NMR data are as follows:

[0121] Compound 1.2: 1 H NMR (600 MHz, Chloroform-d) δ 3.97 (d, 1H), 3.68 (d, 1H), 3.53 (dd, 2H), 3.82 (dq, 1H), 3.60 - 3.28 (m, 3H).

[0122] Compound 1.3: 1 H NMR (600 MHz, Chloroform-d) δ 4.02 (d, 2H), 3.55 (d, 2H), 3.91 - 3.74 (m, 2H), 3.57 - 3.34 (m, 2H).

[0123] Example 3: Preparation of Compound 2.1

[0124] (1) Preparation of Intermediate 4,4'-Dichloro-2,2'-difluoro-1,1'-biphenyl

[0125]

[0126] To a 250 mL three-necked flask was added Intermediate VI (64.2 g, 0.31 mol), which was dissolved in 300 mL of ethyl acetate. Concentrated hydrochloric acid was added dropwise with stirring at room temperature until salt formation was complete. The mixture was filtered by suction and dried to obtain 7.1 of the hydrochloride salt. 1 HNMR (600 MHz, DMSO-d6) δ 5.15 (s, 6H), 3.57 - 3.38 (m, 2H), 3.25 - 3.05 (m, 4H).

[0127] 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 dropwise add sodium nitrite (51.8 g, 0.75 mol). The addition is completed in half an hour. After continuing to stir for 2 h, dropwise add the prepared diazonium salt 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 by flash column chromatography to obtain 64.2 g, namely the intermediate 4,4'-dichloro-2,2'-difluoro-1,1'-biphenyl, with a yield of 80.1%. 1 H NMR (600 MHz, Chloroform-d) δ 3.31 - 3.28 (m, 2H), 3.23 (d, 2H), 3.22 - 3.19 (m, 2H).

[0128] (2) Preparation of intermediate 4,4'-dichloro-6,6'-difluoro-[1,1'-biphenyl]-3,3'-disulfonyl dichloride (6.2)

[0129]

[0130] Compound 6.2 can be prepared from the intermediate 4,4'-dichloro-2,2'-difluoro-1,1'-biphenyl according to the method described in step (4) of Example 1, with a yield of 94.5%. 1 H NMR (600 MHz, DMSO-d6) δ 3.94 - 3.89 (m, 2H), 3.59 - 3.50 (m, 2H).

[0131] (3) Preparation of intermediate 4,4'-dichloro-6,6'-difluoro-[1,1'-biphenyl]-3,3'-dithiol (5.3)

[0132]

[0133] Intermediate 5.4 and intermediate 5.3 can be prepared from intermediate 6.2 according to the method described in step (5) of Example 1.

[0134] (4) Preparation of compound 2.1

[0135]

[0136] Compound 2.1 can be prepared from compound 5.3 according to the method described in step (6) of Example 1. 11H NMR (600 MHz, Chloroform-d) δ 3.70 - 3.58 (m, 2H), 3.41 - 3.30 (m, 2H), 3.45 (q, 4H).

[0137] Example 4: Preparation of Compounds 2.2 and 2.3

[0138]

[0139] Compounds 2.2 and 2.3 can be prepared from Compound 2.1 according to the method described in Example 2. The NMR data are as follows:

[0140] Compound 2.2: 1 1H NMR (600 MHz, Chloroform-d) δ 3.98 (d, 1H), 3.68 (d, 1H), 3.40 - 3.34 (m, 2H), 3.84 - 3.74 (m, 1H), 3.51 - 3.40 (m, 3H).

[0141] Compound 2.3: 1 1H NMR (600 MHz, Chloroform-d) δ 4.05 - 4.00 (m, 2H), 3.41 - 3.36 (m, 2H), 3.84 - 3.73 (m, 2H), 3.53 - 3.41 (m, 2H).

[0142] Biological Activity Assay

[0143] Example 5: Activity Assay against Tetranychus cinnabarinus Adults

[0144] The acaricidal activity of the compounds of the present invention was assayed in a greenhouse. The assay method is as follows:

[0145] 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%.

[0146] Two true leaf kidney bean seedlings were taken, inoculated with Tetranychus cinnabarinus adults and the initial number was investigated. Then, the whole plants were sprayed with a hand-held sprayer. Each treatment had 3 replicates. After treatment, they were placed in a standard observation room. After 72 hours, the number of surviving mites was investigated and the mortality was calculated.

[0147] The test results are shown in Table 5:

[0148] Table 5 Activity Assay Results against Tetranychus cinnabarinus Adults

[0149] [[ID=?]]

Claims

1. A biphenyl compound, characterized in that: The compound is shown in general formula I: In general formula I: R1 is selected from fluorine, chlorine, bromine or iodine; R2 is selected from -CF3, -CHF2, -CH2F, -CH2CF3, -CH2CHF2 or -CH2CH2F; m is selected from 0 or 1; n is selected from 0 or 1.

2. A method for preparing the biphenyl compound as described in claim 1, 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 chlorine or bromine; R2 is selected from -CF3, -CHF2, -CH2F, -CH2CF3, -CH2CHF2 or -CH2CH2F; m is selected from 0 or 1; n is selected from 0 or 1; X is selected from hydrogen or acetyl; Y is selected from HCl, HBr, H2SO4 or HBF4.

3. A compound, which is an intermediate for preparing the biphenyl compound as described in claim 1, characterized in that, The compound has the structure shown in general formula II as follows: In general formula II: R1 is selected from chlorine or bromine; X is selected from hydrogen or acetyl.

4. A compound, which is an intermediate for preparing the compound as claimed in claim 3, characterized in that, The compound has the structure shown in general formula III as follows: In general formula III: R1 is selected from chlorine or bromine.

5. A compound, characterized in that, The compound is the hydrochloride, hydrobromide, sulfate or fluoroborate compound of compound VI as described in claim 2, and the salt compound has the structure shown in general formula V as follows: In general formula V: Y is selected from HCl, HBr, H2SO4 or HBF4.

6. Use of the compound of general formula V as described in claim 5 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.

7. Use of the compound of general formula I as described in claim 1 as a miticide in the agricultural or forestry field.

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

9. A method for controlling agricultural or forestry pest mites, characterized in that: Apply an effective amount of the composition as described in claim 8 to the mites to be controlled or their growth medium.

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