Preparation method of pyroxasulfone

Abstract

The invention provides a novel preparation method of pyroxasulfone. The preparation method provided by the invention has the advantages of high reaction yield, high product purity, mild reaction conditions, short reaction time and short reaction route. Moreover, the preparation method provided by the invention has the advantages of easily available raw materials, low cost, good safety, no need of using a chlorination reagent, few generated three wastes, environmental friendliness and suitability for green large-scale production.

Description

Technical Field

[0001] The invention relates to the technical field of organic synthesis, and in particular to a method for preparing sulfonepyraclostrobin. Background Art

[0002] Pyroxasulfone (CAS No. 447399-55-5) is an isoxazole herbicide developed by Kuibo Chemical Co., Ltd. Its chemical structure is shown below:

[0003]

[0004] Pyroxasulfone

[0005] Sulfonepyraclostrobin is a broad-spectrum herbicide, and its mechanism of action is similar to that of acetochlor and its related herbicides. After application, it is absorbed by the young roots and shoots of weeds, inhibiting the early growth of seedlings, destroying meristems and coleoptiles, and is a potential inhibitor of VLCFA (very long side chain fatty acids) biosynthesis in plants, but it is applied to a wide variety of crops and its biological activity is far greater than that of acetochlor and isopropylmethachlor. In addition, in terms of unit area usage, sulfonepyraclostrobin is 8-10 times lower than acetochlor and other chloroacetamide herbicide varieties, and its solubility in water is low (3.1 mg / L at 20°C), which means that it is unlikely to pollute surface water and groundwater through rainfall and leaching, which can reduce damage to the ecology.

[0006] The weed control spectrum of sulfonepyraclostrobin is similar to that of chloroacetamide herbicides such as acetochlor and isopropylamine, but its control effect on almost all weeds such as hemp, ragweed, broadleaf brachiaria, millet, and foxtail is better than isopropylamine, and the control effect is stable for up to 85 days after spraying; under drought conditions, its effect on controlling green foxtail, sunflower and amaranth is better than S-isopropylamine; low doses have a long effective period for controlling various weeds. The outstanding features of sulfonepyraclostrobin are low dosage per unit area, good weed control effect and long weed control period, and it may partially replace varieties such as acetochlor and isopropylamine in the future.

[0007] In the preparation method of sulfonepyraclostrobin disclosed in the prior art, the reaction route is long, the operation process is complicated, and a chlorination step is required; or, the preparation method needs to use an expensive cyclic secondary amine reagent, which not only increases the production cost, but also the cyclic secondary amine reacts with the hydrochloric acid in the system to generate a cyclic ammonium chloride salt, which is not conducive to the reaction. In addition, the existing method also has the problems of low yield of sulfonepyraclostrobin, low raw material conversion rate, large amount of by-products, difficult post-processing, and easy to cause environmental pollution. Summary of the invention

[0008] In order to solve the above technical problems, the present invention provides a method for preparing sulfonepyraclostrobin, wherein the preparation method comprises the following steps:

[0009] Step S5: reacting the compound of formula (6) with sodium hypochlorite to obtain sulfonepyraclostrobin represented by formula (1);

[0010]

[0011] According to an embodiment of the present invention, in step S5, the molar ratio of the compound of formula (6) to sodium hypochlorite is 1:(1-8), preferably 1:(1.5-5), for example 1:2, 1:2.5, 1:3, 1:3.5 or 1:4.

[0012] According to an embodiment of the present invention, step S5 is carried out in the presence of an organic solvent. For example, the organic solvent is selected from one, two or more of methanol, ethanol, ethylene glycol dimethyl ether, diethylene glycol dimethyl ether, tetrahydrofuran, toluene, dichloroethane, dichloromethane, N,N-dimethylformamide (DMF), N,N-dimethylacetamide (DMAC), sulfolane, and acetonitrile.

[0013] According to an embodiment of the present invention, the weight ratio of the amount of the compound of formula (6) to the organic solvent is selected from 1 mol: (100-1000) g, for example 1 mol: (200-800) g, such as 1 mol: 300 g, 1 mol: 400 g, 1 mol: 500 g, 1 mol: 600 g, 1 mol: 700 g.

[0014] According to an embodiment of the present invention, the reaction temperature of step S5 is 40°C to 120°C, preferably 60°C to 100°C, for example 60°C, 65°C, 70°C, 75°C, 80°C, 85°C, 90°C, 95°C or 100°C.

[0015] According to an embodiment of the present invention, the reaction time of step S5 is 0.5h-10h, for example, 1h, 2h, 3h, 4h, 5h, 6h, 7h, 8h.

[0016] According to an embodiment of the present invention, after the reaction in step S5 is completed, the organic solvent is removed and extraction and separation are performed using water or an organic extraction solvent (such as ethyl acetate or dichloromethane); preferably, after extraction, the organic phase is desolventized, toluene is added, and recrystallization and purification are performed.

[0017] According to an embodiment of the present invention, during extraction, the weight ratio of the amount of the compound of formula (6) to water is selected from 1 mol: (50-800) g, for example 1 mol: (100-500) g, such as 1 mol: 200 g, 1 mol: 300 g, 1 mol: 400 g.

[0018] According to an embodiment of the present invention, during extraction, the weight ratio of water to the organic extraction solvent is selected from 1:(0.2-5), for example 1:(0.5-2), such as 1:0.5, 1:1, 1:1.5.

[0019] According to an embodiment of the present invention, during recrystallization purification, the weight ratio of the amount of the compound of formula (6) to the toluene is selected from 1 mol: (100-1000) g, for example 1 mol: (200-800) g, such as 1 mol: 300 g, 1 mol: 400 g, 1 mol: 500 g, 1 mol: 600 g, 1 mol: 700 g.

[0020] According to an embodiment of the present invention, the preparation method of step S5 comprises: adding a compound of formula (6) and an organic solvent to a reactor in sequence, heating, and then adding sodium hypochlorite to react to obtain sulfonepyraclostrobin represented by formula (1).

[0021] According to an embodiment of the present invention, the method for preparing the compound of formula (6) comprises the following steps:

[0022] Step S4: synthesizing a compound of formula (6) from a compound of formula (5) in the presence of an oxidant and a catalyst;

[0023]

[0024] According to an embodiment of the present invention, in step S4, the molar ratio of the compound of formula (5) to the oxidant is 1:(1-10), preferably 1:(2-8), for example 1:3, 1:4, 1:5, 1:6, 1:7, 1:8.

[0025] According to an embodiment of the present invention, in step S4, the oxidant is selected from one, two or more of hydrogen peroxide, oxygen, meta-chloroperoxybenzoic acid, and sodium percarbonate.

[0026] According to an embodiment of the present invention, in step S4, when the oxidant is hydrogen peroxide, the hydrogen peroxide is an aqueous solution of hydrogen peroxide, and the concentration is, for example, 10wt%-50wt%, such as 20wt%, 30wt%, 40wt%.

[0027] According to an embodiment of the present invention, in step S4, the molar ratio of the compound of formula (5) to the catalyst is 1:(0.01-5), preferably 1:(0.1-2.0), for example 1:0.2, 1:0.5, 1:1, 1:1.5, 1:2.

[0028] According to an embodiment of the present invention, in step S4, the catalyst is a mixed acid, for example, a mixed acid of sulfuric acid and acetic acid; the molar ratio of sulfuric acid to acetic acid can be 1:(2-10), for example 1:(5-8), such as 1:4, 1:4.5, 1:5, 1:5.5, 1:6, 1:6.5, 1:7, 1:7.5, 1:8, 1:8.5.

[0029] According to an embodiment of the present invention, step S4 is carried out in the presence of an organic solvent. For example, the organic solvent is selected from one, two or more of ethylene glycol dimethyl ether, diethylene glycol dimethyl ether, tetrahydrofuran, toluene, dichloroethane, dichloromethane, N,N-dimethylformamide (DMF), N,N-dimethylacetamide (DMAC), sulfolane, and acetonitrile; for example, toluene.

[0030] According to an embodiment of the present invention, the reaction temperature of step S4 is -10°C to 150°C, preferably 30°C to 70°C, for example 30°C, 35°C, 40°C, 45°C, 50°C, 55°C, 60°C, 65°C or 70°C.

[0031] According to an embodiment of the present invention, the reaction time of step S4 is 0.2h-5h, for example 0.5h, 1h, 2h, 3h, 4h, 5h.

[0032] According to an embodiment of the present invention, after the reaction in step S4 is completed, the solvent is removed or the reaction is directly used in subsequent reactions without post-treatment.

[0033] According to an embodiment of the present invention, the preparation method of step S4 comprises: sequentially adding a compound of formula (5), acetic acid, sulfuric acid, and an organic solvent into a reactor, and after heating, adding a hydrogen peroxide aqueous solution to react to obtain a compound of formula (6).

[0034] According to an embodiment of the present invention, the method for preparing the compound of formula (5) comprises the following steps:

[0035] Step S3: reacting the compound of formula (4) with freon in the presence of a base to obtain a compound of formula (5);

[0036]

[0037] According to an embodiment of the present invention, in step S3, the molar ratio of the compound of formula (5), freon and base is 1:(1-5):(1-5), preferably 1:(1.1-2.0):(1.1-2.0), for example 1:2:2. Each of the "1.1-2.0" at least records 1.1, 1.2, 1.3, 1.4, 1.5, 1.6, 1.7, 1.8, 1.9 or 2.0.

[0038] According to an embodiment of the present invention, in step S3, the base is selected from one, two or more of organic bases and inorganic bases, for example, selected from one, two or more of sodium hydroxide, potassium hydroxide, sodium hydride, potassium tert-butoxide, sodium tert-butoxide, triethylamine, etc., for example, sodium hydroxide.

[0039] According to an embodiment of the present invention, in step S3, the alkali may be an aqueous solution of alkali, with a concentration of, for example, 10 wt%-50 wt%, such as 20 wt%, 30 wt%, or 40 wt%.

[0040] According to an embodiment of the present invention, step S3 is carried out in the presence of water and / or an organic solvent. For example, the organic solvent is selected from one, two or more of ethylene glycol dimethyl ether, diethylene glycol dimethyl ether, tetrahydrofuran, toluene, dichloroethane, dichloromethane, N,N-dimethylformamide (DMF), N,N-dimethylacetamide (DMAC), sulfolane, and acetonitrile; for example, water and acetonitrile; the volume ratio of water to the organic solvent can be (1-5):10, such as 2:10, 3:10, and 4:10.

[0041] According to an embodiment of the present invention, the reaction temperature of step S3 is -10°C to 50°C, preferably 0°C to 30°C, such as 10°C, 15°C, 20°C, 25°C or 30°C.

[0042] According to an embodiment of the present invention, the reaction time of step S3 is 0.5h-8h, for example, 1h, 2h, 3h, 4h, 5h, 6h.

[0043] According to an embodiment of the present invention, the preparation method of step S3 is specifically as follows: adding the compound of formula (4), an organic solvent and a base into a reactor in sequence, and then introducing freon at a low temperature (10-20° C.) to react, thereby obtaining the compound of formula (5).

[0044] According to an embodiment of the present invention, the preparation method of the compound of formula (4) comprises the following steps:

[0045] Step S2: reacting the compound of formula (3) with methylhydrazine to obtain a compound of formula (4);

[0046]

[0047] Wherein, R is selected from C1-C8 alkyl, C3-C8 cycloalkyl, C3-C8 halogenated cycloalkyl; preferably, R is selected from C1-C6 alkyl; more preferably, it is methyl.

[0048] According to an embodiment of the present invention, step S2 is carried out in the presence of water and / or an organic solvent. For example, the organic solvent is selected from one, two or more of methanol, ethanol, acetonitrile, etc. For example, the volume ratio of water to the organic solvent is (1-9): (9-1), such as (2-8): (8-2), (3-7): (7-3), (4-6): (6-4) or 1:1.

[0049] According to an embodiment of the present invention, the volume ratio of the amount of the compound of formula (3) to the organic solvent in step S2 is selected from 1 mol: (100-1000) mL, for example 1 mol: (200-800) mL, such as 1 mol: 300 mL, 1 mol: 400 mL, 1 mol: 500 mL, 1 mol: 600 mL, 1 mol: 700 mL.

[0050] According to an embodiment of the present invention, in step S2, the molar ratio of the compound of formula (3) to methylhydrazine is (0.5-5):(0.5-5), preferably (1.0-3.0):(1.0-3.0), for example, 1:2, 1:1, etc. Wherein, each of the "1.0-3.0" at least records 1.0, 1.1, 1.2, 1.3, 1.4, 1.5, 1.6, 1.7, 1.8, 1.9, 2.0, 2.1, 2.2, 2.3, 2.4, 2.5, 2.6, 2.7, 2.8, 2.9 or 3.0.

[0051] According to an embodiment of the present invention, the reaction temperature of step S2 is 10-100°C, preferably 30°C to 70°C, for example 30°C, 35°C, 40°C, 45°C, 50°C, 55°C, 60°C, 65°C or 70°C.

[0052] According to an embodiment of the present invention, the reaction time of step S2 is 0.5h-5h, for example, 1h, 2h, 3h, 4h, 5h.

[0053] According to an embodiment of the present invention, after the reaction of the preparation method in step S2 is completed, extraction with ethyl acetate is performed and solvent removal is performed to obtain a compound of formula (4).

[0054] According to an embodiment of the present invention, after the reaction in step S2 is completed, it can be directly used in subsequent reactions without post-treatment.

[0055] According to an embodiment of the present invention, the preparation method of step S2 comprises: adding an organic solvent and methylhydrazine in sequence to a reactor containing a compound of formula (3), and reacting after heating to obtain a compound of formula (4).

[0056] According to an embodiment of the present invention, the method for preparing the compound of formula (3) comprises the following steps:

[0057] Step S1: reacting the compound of formula (2) with trifluoroacetaldehyde in the presence of a base to obtain a compound of formula (3);

[0058]

[0059] Wherein, R is selected from C1-C8 alkyl, C3-C8 cycloalkyl, C3-C8 halogenated cycloalkyl; preferably, R is selected from C1-C6 alkyl; more preferably, it is methyl.

[0060] According to an embodiment of the present invention, in step S1, the molar ratio of the compound of formula (2), trifluoroacetaldehyde and the base is 1:(1-5):(1-5), preferably 1:(1.1-2.0):(1.1-2.0), for example 1:1.1:1.1. Each of the "1.1-2.0" at least records 1.1, 1.2, 1.3, 1.4, 1.5, 1.6, 1.7, 1.8, 1.9 or 2.0.

[0061] According to an embodiment of the present invention, in step S1, the base is selected from one, two or more of organic bases and inorganic bases, for example, one, two or more of sodium hydroxide, potassium hydroxide, sodium hydride, potassium tert-butoxide, sodium tert-butoxide, triethylamine, etc., for example, sodium hydroxide.

[0062] According to an embodiment of the present invention, in step S1, the alkali may be an aqueous solution of alkali, and the concentration thereof may be, for example, 10 wt%-50 wt%, such as 20 wt%, 30 wt%, or 40 wt%.

[0063] According to an embodiment of the present invention, step S1 is carried out in the presence of an organic solvent. For example, the organic solvent is selected from one, two or more of methanol, ethanol, ethylene glycol dimethyl ether, diethylene glycol dimethyl ether, tetrahydrofuran, toluene, dichloroethane, dichloromethane, N,N-dimethylformamide (DMF), N,N-dimethylacetamide (DMAC), sulfolane, and acetonitrile; for example, ethanol.

[0064] According to an embodiment of the present invention, the volume ratio of the amount of the compound of formula (2) to the organic solvent in step S1 is selected from 1 mol: (100-1000) mL, for example 1 mol: (200-800) mL, such as 1 mol: 300 mL, 1 mol: 400 mL, 1 mol: 500 mL, 1 mol: 600 mL, 1 mol: 700 mL.

[0065] According to an embodiment of the present invention, the reaction temperature of step S1 is -10°C to 150°C, preferably 30°C to 70°C, for example 30°C, 35°C, 40°C, 45°C, 50°C, 55°C, 60°C, 65°C or 70°C.

[0066] According to an embodiment of the present invention, the reaction time of step S1 is 0.5h-8h, for example, 1h, 2h, 3h, 4h, 5h, 6h.

[0067] According to an embodiment of the present invention, the preparation method of step S1 is specifically as follows: adding the compound of formula (2), an organic solvent, and a base to a reactor in sequence, and after heating, adding trifluoroacetaldehyde to react to obtain a compound of formula (3).

[0068] According to an embodiment of the present invention, in the preparation method of step S1, after the reaction is completed, the product is cooled for crystallization, filtered under reduced pressure, and dried to obtain a compound of formula (3).

[0069] The present invention also provides the intermediate compound shown below:

[0070]

[0071] Wherein, R is selected from C1-C8 alkyl, C3-C8 cycloalkyl, C3-C8 halogenated cycloalkyl; preferably, R is selected from C1-C6 alkyl; more preferably, it is methyl.

[0072] The present invention also provides application of the intermediate compound in the preparation of sulfonepyraclostrobin.

[0073] Beneficial Effects

[0074] The present invention provides a novel preparation method of sulfonepyraclostrobin. The preparation method provided by the present invention has high reaction yield, high product purity, mild reaction conditions, short reaction time and short reaction route. In addition, the preparation method provided by the present invention has easy-to-obtain raw materials, low cost, good safety, no need to use chlorination reagents, less three wastes, excellent environmental friendliness, and is suitable for green large-scale production. DETAILED DESCRIPTION

[0075] The technical scheme of the present invention will be further described in detail below in conjunction with specific embodiments. It should be understood that the following embodiments are only exemplary descriptions and explanations of the present invention and should not be construed as limiting the scope of protection of the present invention. All technologies implemented based on the above content of the present invention are included in the scope that the present invention is intended to protect.

[0076] In the following examples, unless otherwise specified, all raw materials used were purchased from Beijing Coupling Technology Co., Ltd.

[0077] In the following examples, the contents (purity) of reactants and products were measured by high performance liquid chromatography (Agilent HPLC1260).

[0078] Example 1: Synthesis of Compound 5

[0079] In a 500mL four-necked flask, add 1 mol of compound 2, then add 500mL of anhydrous ethanol and 1.1mol of 30wt% sodium hydroxide, stir, heat to about 50°C, add 1.1mol of trifluoroacetaldehyde aqueous solution dropwise, keep at 50°C for 5h, cool and crystallize, filter under reduced pressure, and dry to obtain a yellow solid compound 3.

[0080] The compound 3 obtained above was added to the reactor, and 500 ml of methanol and 1.2 mol of methylhydrazine were added, and the mixture was heated to 65-70°C for 2 h. The reaction was considered complete when the liquid phase detection area of ​​compound 3 was less than 0.1%, and compound 4 was obtained, which was used directly in the next step without further treatment. M / Z was 311.09.

[0081] 30 mL of water, 100 mL of acetonitrile, and 2 mol of 30 wt% aqueous sodium hydroxide solution were added to the reaction solution in the previous step. At 10-20°C, 2.0 mol of freon (1-chloro-2-fluoromethane) was introduced. The reaction was carried out at 20°C for 3 h. The area of ​​compound 4 detected by liquid phase was less than 0.1%, and the reaction was considered to be complete. After extraction with ethyl acetate and desolventization, compound 5 was obtained with a yield of 85% and a purity of 95%. M / Z was 361.09.

[0082] The reaction scheme is as follows, where R is methyl:

[0083]

[0084] Example 2: Synthesis of Compound 6

[0085] In a 500mL four-necked bottle, add compound 5 (1mol), acetic acid 1.5mol, sulfuric acid 0.2mol, toluene 100g, heat to 40-50°C, start to drop 30wt% hydrogen peroxide aqueous solution 5mol, dropwise addition is completed in 2h, keep warm and react for 1h, liquid HPLC detection compound 5 area is less than 0.5%, the reaction is complete, standstill, demix, remove the solvent to obtain white solid compound 6, the yield is 95.0% (based on compound 5), the content is 94.5%. M / Z is 393.08.

[0086] The reaction route is as follows:

[0087]

[0088] Example 3: Synthesis of Compound 1

[0089] In a 2000mL four-necked flask, compound 6 (1 mol) and 500 g of methanol were added. After heating to 65-70°C, 3 mol of sodium hypochlorite was added dropwise and the reaction was carried out for 1 h. The area of ​​compound 6 detected by liquid HPLC was less than 0.1%. The reaction was completed to obtain the methanol mother liquor of compound 1. After the solvent was recovered by vacuum distillation, 500 g of water and 500 g of ethyl acetate were added, and the layers were extracted. After the organic phase was freed of the solvent, 300 g of toluene was added and recrystallized to obtain the target compound 1 sulfonepyraclostrobin with a content of 99% and a yield of 98% (based on compound 6).

[0090] The reaction route is as follows:

[0091]

[0092] The white solid product synthesized by the above route was subjected to NMR detection, and the results are as follows: 1 H NMR (400 MHz, CDCl3) δ: 6.83 (t, J = 71.9 Hz, 1H), 4.60 (s, 2H), 3.88 (s, 3H), 3.11 (s, 2H), 1.52 (s, 6H). It can be seen that the white solid prepared in this example is pyraclostrobin.

[0093] The preferred embodiments of the present invention are described in detail above. However, the protection scope of the present application is not limited thereto. Within the technical concept of the present invention, those skilled in the art may make various modifications to the technical solution of the present invention, including combining various technical features in any other suitable manner, and these simple modifications and combinations should also be included in the protection scope of the claims of the present application.

Claims

1. A method for preparing sulfonepyraclostrobin, wherein the method comprises the following steps: Step S5: reacting the compound of formula (6) with sodium hypochlorite to obtain sulfonepyraclostrobin represented by formula (1); Preferably, in step S5, the molar ratio of the compound of formula (6) to sodium hypochlorite is 1:(1-8), preferably 1:(1.5-5); Preferably, step S5 is carried out in the presence of an organic solvent; for example, the organic solvent is selected from one, two or more of methanol, ethanol, ethylene glycol dimethyl ether, diethylene glycol dimethyl ether, tetrahydrofuran, toluene, dichloroethane, dichloromethane, N,N-dimethylformamide (DMF), N,N-dimethylacetamide (DMAC), sulfolane, and acetonitrile; Preferably, the reaction temperature of step S5 is 40°C to 120°C, preferably 60°C to 100°C; Preferably, the reaction time of step S5 is 0.5h-10h.

2. The preparation method according to claim 1, characterized in that: After the reaction in step S5 is completed, the organic solvent is removed, and extraction and separation are performed using water or an organic extraction solvent (such as ethyl acetate or dichloromethane); preferably, after extraction, the organic phase is desolventized, toluene is added, and recrystallization and purification are performed; Preferably, during the recrystallization purification, the weight ratio of the amount of the compound of formula (6) to the toluene is selected from 1 mol: (100-1000) g, for example 1 mol: (200-800) g; Preferably, the preparation method of step S5 comprises: sequentially adding a compound of formula (6) and an organic solvent into a reactor, heating, and then adding sodium hypochlorite to react to obtain sulfonepyraclostrobin represented by formula (1).

3. The preparation method according to claim 1 or 2, characterized in that: The preparation method of the compound of formula (6) comprises the following steps: Step S4: synthesizing a compound of formula (6) from a compound of formula (5) in the presence of an oxidant and a catalyst; Preferably, in step S4, the molar ratio of the compound of formula (5) to the oxidant is 1:(1-10), preferably 1:(2-8); Preferably, in step S4, the oxidant is selected from one, two or more of hydrogen peroxide, oxygen, m-chloroperoxybenzoic acid, and sodium percarbonate; Preferably, in step S4, when the oxidant is hydrogen peroxide, the hydrogen peroxide is a hydrogen peroxide aqueous solution, and the concentration is, for example, 10wt%-50wt%; Preferably, in step S4, the molar ratio of the compound of formula (5) to the catalyst is 1:(0.01-5), preferably 1:(0.1-2.0); Preferably, in step S4, the catalyst is a mixed acid, for example, a mixed acid of sulfuric acid and acetic acid; the molar ratio of sulfuric acid to acetic acid may be 1:(2-10), for example, 1:(5-8).

4. The preparation method according to claim 3, characterized in that: Step S4 is carried out in the presence of an organic solvent. For example, the organic solvent is selected from one, two or more of ethylene glycol dimethyl ether, diethylene glycol dimethyl ether, tetrahydrofuran, toluene, dichloroethane, dichloromethane, N,N-dimethylformamide (DMF), N,N-dimethylacetamide (DMAC), sulfolane, and acetonitrile; for example, toluene; Preferably, the reaction temperature of step S4 is -10°C to 150°C, preferably 30°C to 70°C; Preferably, the reaction time of step S4 is 0.2h-5h; Preferably, the preparation method of step S4 comprises: sequentially adding a compound of formula (5), acetic acid, sulfuric acid, and an organic solvent into a reactor, and after heating, adding a hydrogen peroxide aqueous solution to react to obtain a compound of formula (6).

5. The preparation method according to any one of claims 1 to 4, characterized in that: The preparation method of the compound of formula (5) comprises the following steps: Step S3: reacting the compound of formula (4) with freon in the presence of a base to obtain a compound of formula (5); Preferably, in step S3, the molar ratio of the compound of formula (5), freon and base is 1:(1-5):(1-5), preferably 1:(1.1-2.0):(1.1-2.0); Preferably, in step S3, the base is selected from one, two or more of organic bases and inorganic bases, for example, one, two or more of sodium hydroxide, potassium hydroxide, sodium hydride, potassium tert-butoxide, sodium tert-butoxide, triethylamine, etc., for example, sodium hydroxide.

6. The preparation method according to claim 5, characterized in that: Step S3 is carried out in the presence of water and / or an organic solvent; for example, the organic solvent is selected from one, two or more of ethylene glycol dimethyl ether, diethylene glycol dimethyl ether, tetrahydrofuran, toluene, dichloroethane, dichloromethane, N,N-dimethylformamide (DMF), N,N-dimethylacetamide (DMAC), sulfolane, and acetonitrile; Preferably, the reaction temperature of step S3 is -10°C to 50°C, preferably 0°C to 30°C; Preferably, the reaction time of step S3 is 0.5h-8h; Preferably, the preparation method of step S3 is specifically as follows: adding the compound of formula (4), an organic solvent and a base into a reactor in sequence, and then introducing freon at a low temperature (10-20° C.) to react, thereby obtaining the compound of formula (5).

7. The preparation method according to any one of claims 1 to 6, characterized in that: The preparation method of the compound of formula (4) comprises the following steps: Step S2: reacting the compound of formula (3) with methylhydrazine to obtain a compound of formula (4); Wherein, R is selected from C1-C8 alkyl, C3-C8 cycloalkyl, C3-C8 halogenated cycloalkyl; preferably, R is selected from C1-C6 alkyl; more preferably, it is methyl; Preferably, step S2 is carried out in the presence of water and / or an organic solvent; for example, the organic solvent is selected from one, two or more of methanol, ethanol, acetonitrile, etc.; Preferably, in step S2, the volume ratio of the amount of the compound of formula (3) to the organic solvent is selected from 1 mol: (100-1000) mL, for example 1 mol: (200-800) mL; Preferably, in step S2, the molar ratio of the compound of formula (3) to methylhydrazine is (0.5-5):(0.5-5), preferably (1.0-3.0):(1.0-3.0); Preferably, the reaction temperature of step S2 is 10-100°C, preferably 30°C to 70°C; Preferably, the reaction time of step S2 is 0.5h-5h; Preferably, the preparation method of step S2 comprises: adding an organic solvent and methylhydrazine to a reactor containing the compound of formula (3) in sequence, and reacting after heating to obtain the compound of formula (4).

8. The preparation method according to any one of claims 1 to 7, characterized in that: The preparation method of the compound of formula (3) comprises the following steps: Step S1: reacting the compound of formula (2) with trifluoroacetaldehyde in the presence of a base to obtain a compound of formula (3); Wherein, R is selected from C1-C8 alkyl, C3-C8 cycloalkyl, C3-C8 halogenated cycloalkyl; preferably, R is selected from C1-C6 alkyl; more preferably, it is methyl; Preferably, in step S1, the molar ratio of the compound of formula (2), trifluoroacetaldehyde and the base is 1:(1-5):(1-5), preferably 1:(1.1-2.0):(1.1-2.0); Preferably, in step S1, the base is selected from one, two or more of organic bases and inorganic bases, for example, one, two or more of sodium hydroxide, potassium hydroxide, sodium hydride, potassium tert-butoxide, sodium tert-butoxide, triethylamine, etc., for example, sodium hydroxide.

9. The preparation method according to claim 8, characterized in that: Step S1 is carried out in the presence of an organic solvent; for example, the organic solvent is selected from one, two or more of methanol, ethanol, ethylene glycol dimethyl ether, diethylene glycol dimethyl ether, tetrahydrofuran, toluene, dichloroethane, dichloromethane, N,N-dimethylformamide (DMF), N,N-dimethylacetamide (DMAC), sulfolane, and acetonitrile; for example, ethanol; Preferably, the reaction temperature of step S1 is -10°C to 150°C, preferably 30°C to 70°C; Preferably, the reaction time of step S1 is 0.5h-8h.

10. The preparation method according to claim 8, characterized in that: The preparation method of step S1 is specifically as follows: adding the compound of formula (2), an organic solvent and a base into a reactor in sequence, heating, and then adding trifluoroacetaldehyde to react to obtain the compound of formula (3).

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