Synthesis method of fluopyram

Abstract

The invention provides a fluopyram synthesis method, which comprises: (1) in the presence of a catalyst, carrying out a reaction on o-trifluoromethyl benzoic acid and triphosgene in a solvent to obtain o-trifluoromethyl benzoyl chloride; and (2) directly reacting the o-trifluoromethyl benzoyl chloride with the 3-chloro-2-aminoethyl-5-trifluoromethylpyridine or the hydrochloride of the 3-chloro-2-aminoethyl-5-trifluoromethylpyridine in a solvent to obtain the target product fluopyram. In the preparation method, solid phosgene is used as a raw material in the step (1), only hydrogen chloride and carbon dioxide are generated, sulfur elements are not contained, and tail gas is easier to treat; an acid-binding agent is not used in the step (2), so that the raw material cost is saved; in the step (2), introduction of water and salt is avoided, a target product can be obtained through cooling crystallization after the reaction is finished, and the process is simpler and easy to operate; and the preparation method is high in yield and suitable for industrial production.

Description

Technical Field

[0001] The invention belongs to the technical field of synthesis and application of fine chemical products and relates to a method for synthesizing fluopyram. Background Art

[0002] Fluopyram (abbreviated as: Fluopyram) is a new type of benzamide broad-spectrum fungicide with high efficiency and low toxicity. It is also an excellent nematicide. It can be applied to a variety of diseases of more than 70 kinds of crops. It is mainly used to prevent and control gray mold, powdery mildew, downy mildew, etc. caused by fungal pathogens. It has great development potential.

[0003] There are two main existing synthesis processes for fluopyram:

[0004] Route 1 (CN101080391):

[0005]

[0006] This route uses 2,3-dichloro-5-trifluoromethylpyridine, diethyl malonate and o-trifluoromethylbenzoic acid as starting materials, and obtains the final product, fluopyram, through 7 steps of reaction. This route has a long synthesis process, and the previous step of synthesizing fluopyram requires a decarboxylation reaction at 180°C for 24 hours, with a yield of only about 66%, which is not suitable for large-scale industrial production.

[0007] Route 2:

[0008]

[0009] According to literature reports, there are several methods for preparing o-trifluoromethylbenzoyl chloride of formula I, such as: US2010160323A1 (2010) discloses that oxalyl chloride is reacted with o-trifluoromethylbenzoic acid to obtain formula I, with a yield of 100%; CN108947892A (2018) discloses that thionyl chloride is reacted with o-trifluoromethylbenzoic acid to obtain formula I, with a yield of 98.7%; Literature (Ranjana Bisht, Md Emdadul Hoque, Prof. Dr. Buddhadeb ChattopadhyayAmide; Effects in CH Activation: Noncovalent Interactions with L-Shaped Ligand formeta Borylation of Aromatic Amides; Angewandte Chemie-International Edition, 2018, vol. 57, # 48, p. 15762-15766) reported that a dichloromethane solution of phosgene was reacted with o-trifluoromethylbenzoic acid to prepare formula I, but specific examples and yields were not disclosed.

[0010] CN101080390B (ZL2005800435587) discloses a condensation reaction of Formula I and Formula II to obtain fluopyram, wherein an acid-binding agent such as triethylamine, sodium hydroxide, potassium carbonate, etc. is required in each condensation step.

[0011] In the above preparation method, the synthesis process of Formula I and Fluopyram has the following problems:

[0012] 1) In the preparation process of Formula IV, when chlorination with oxalyl chloride, although the yield is 100%, about 0.45 tons of oxalyl chloride (unit price is about 40,000 / ton) is required for each ton of fluopyram, and the cost is about 18,000 yuan; when chlorination with thionyl chloride is used, about 0.42 tons of thionyl chloride (unit price is about 2,000 / ton) is required for each ton of fluopyram, and the cost is about 840 yuan, but the reaction process produces equimolar amounts of sulfur dioxide and hydrogen chloride mixed acidic gas, and no economical and effective separation method has been found; chlorination with phosgene solution theoretically only produces carbon dioxide and hydrogen chloride, and there are relatively mature hydrochloric acid recovery devices in the industry, and laboratories generally absorb it through alkaline solution. However, phosgene is a highly toxic chemical that is difficult to transport and store, and its use conditions are limited;

[0013] 2) In the preparation process of fluopyram, an acid-binding agent (such as triethylamine, sodium hydroxide, etc.) is required in the reaction process of formula I and formula II or formula III to fully convert the raw materials. For example, when sodium hydroxide is used as an acid-binding agent, about 1.2 tons of 20% sodium chloride salt solution is produced per ton of fluopyram, and the salt solution belongs to high-concentration saline wastewater.

[0014] Therefore, how to solve the problems of excessive waste, low yield and complicated operation in the condensation reaction step in the synthesis of fluopyram is the research focus in this field. Summary of the invention

[0015] In view of the deficiencies in the prior art, the object of the present invention is to provide a method for synthesizing fluopyram. The present invention uses o-trifluoromethylbenzoic acid as a raw material, prepares an acyl chloride through solid phosgene, does not need to be separated, and then reacts with formula I or its hydrochloride in a system without an auxiliary acid to prepare fluopyram. The process has the advantages of high yield, less three wastes, safe and clean process, high product purity, low cost, and is suitable for industrial production.

[0016] To achieve this object, the present invention adopts the following technical solutions:

[0017] In one aspect, the present invention provides a method for synthesizing fluopyram, the method comprising the following steps:

[0018] (1) In the presence of a catalyst, o-trifluoromethylbenzoic acid reacts with solid phosgene (hereinafter referred to as solid phosgene) in a solvent to obtain o-trifluoromethylbenzoyl chloride;

[0019] (2) o-Trifluoromethylbenzoyl chloride is directly reacted with 3-chloro-2-aminoethyl-5-trifluoromethylpyridine or its hydrochloride in a solvent to obtain the target product fluopyram.

[0020] Reaction equation of the present invention is:

[0021] Step (1):

[0022]

[0023] Step (2):

[0024]

[0025] Preferably, the catalyst in step (1) is any one of a pyridine compound, a dialkylamide compound or a tertiary amine compound, or a combination of at least two thereof.

[0026] Preferably, the pyridine compound is selected from pyridine and / or 4-dimethylaminopyridine (DMAP).

[0027] Preferably, the dialkylamide compound is selected from N,N-dimethylformamide (hereinafter referred to as: DMF) and / or N,N-methylacetamide.

[0028] Preferably, the tertiary amine compound is selected from any one of triethylamine, trimethylamine or N,N-dimethylaniline, or a combination of at least two thereof.

[0029] As mentioned above, the catalyst can be used alone or in combination of two or more.

[0030] Preferably, the amount of the catalyst is 0.001-1.0 times the molar amount of o-trifluoromethylbenzoic acid; for example, 0.001 times, 0.003 times, 0.005 times, 0.008 times, 0.01 times, 0.03 times, 0.05 times, 0.1 times, 0.5 times, 0.8 times or 1.0 times.

[0031] Preferably, the catalyst is a combination of pyridine and N,N-dimethylformamide, wherein the amount of pyridine is 0.001-0.5 times (e.g., 0.001 times, 0.003 times, 0.005 times, 0.008 times, 0.01 times, 0.03 times, 0.05 times, 0.1 times or 0.5 times) the molar amount of o-trifluoromethylbenzoic acid, and the amount of N,N-dimethylformamide is 0.001-0.5 times (e.g., 0.001 times, 0.003 times, 0.005 times, 0.008 times, 0.01 times, 0.03 times, 0.05 times, 0.1 times or 0.5 times) the molar amount of o-trifluoromethylbenzoic acid.

[0032] Preferably, the molar ratio of o-trifluoromethylbenzoic acid to solid phosgene in step (1) is 1:1.0-10.0; for example, 1:1.0, 1:1.5, 1:2.0, 1:3.0, 1:4.0, 1:5.0, 1:6.0, 1:7.0, 1:8.0, 1:9.0 or 1:10.0, more preferably 1:1.0-3.0.

[0033] Preferably, the solvent for the reaction in step (1) is selected from any one of aromatic solvents, chlorinated alkane solvents, alkane solvents or ether solvents, or a combination of at least two thereof.

[0034] Preferably, the aromatic hydrocarbon solvent is selected from any one of toluene, xylene or chlorobenzene, or a combination of at least two thereof.

[0035] Preferably, the chlorinated alkane solvent is selected from any one of 1,2-dichloroethane, chloroform or carbon tetrachloride, or a combination of at least two thereof.

[0036] Preferably, the alkane solvent is selected from any one or a combination of at least two of pentane, hexane, methylcyclohexane, heptane, cyclopentane, cyclohexane or cycloheptane.

[0037] Preferably, the ether solvent is selected from any one of diethyl ether, tetrahydrofuran or ethylene glycol dimethyl ether, or a combination of at least two thereof.

[0038] Further preferably, the solvent is selected from any one or a combination of at least two of toluene, xylene, 1,2-dichloroethane, cyclohexane or methylcyclohexane.

[0039] Preferably, the amount of the solvent in step (1) is 1.0 to 10.0 times the weight of the solid phosgene; for example, 1.0, 2.0, 3.0, 5.0, 8.0 or 10.0 times. It is particularly preferred that the amount of solvent used is just enough to completely dissolve the solid phosgene required for the feed.

[0040] Preferably, the solid phosgene is added in step (1) by directly adding the solid phosgene or by adding it dropwise after it is dissolved.

[0041] Preferably, the specific implementation method of step (1) is: o-trifluoromethylbenzoic acid, a catalyst and an appropriate amount of solvent are placed in a reactor and stirred evenly; solid phosgene is passed through a solid feeder, and after the reaction temperature is well controlled, the solid phosgene is slowly added to the well-stirred reaction system for reaction.

[0042] Preferably, the reaction temperature in step (1) is -5 to 120°C (e.g., -5°C, 0°C, 10°C, 30°C, 50°C, 80°C, 100°C or 120°C); more preferably, it is 30 to 100°C.

[0043] Preferably, the reaction time of step (1) is 1 to 10 h, for example, 1 h, 2 h, 5 h, 8 h or 10 h.

[0044] Preferably, in step (2), the molar ratio of o-trifluoromethylbenzoyl chloride to 3-chloro-2-aminoethyl-5-trifluoromethylpyridine or its hydrochloride is 1:1.0 to 1.50, for example 1:1.0, 1:1.1, 1:1.2, 1:1.3, 1:1.4 or 1:1.5, more preferably 1:1.05 to 1.2.

[0045] Preferably, the reaction temperature in step (2) is 30 to 200° C. (e.g., 30° C., 50° C., 80° C., 100° C., 120° C., 150° C., 180° C. or 200° C.), preferably 60 to 150° C. It should also be noted that the reaction is sometimes carried out at the boiling point of the solvent used.

[0046] Preferably, the solvent for the reaction in step (2) is selected from any one of aromatic solvents, chlorinated alkane solvents, alkane solvents or ether solvents, or a combination of at least two thereof.

[0047] Preferably, the aromatic hydrocarbon solvent is selected from any one of toluene, xylene or chlorobenzene, or a combination of at least two thereof.

[0048] Preferably, the chlorinated alkane solvent is selected from any one of 1,2-dichloroethane, chloroform or carbon tetrachloride, or a combination of at least two thereof.

[0049] Preferably, the alkane solvent is selected from any one of pentane, hexane, heptane, cyclopentane, cyclohexane or cycloheptane, or a combination of at least two thereof.

[0050] Preferably, the ether solvent is selected from any one of diethyl ether, tetrahydrofuran or ethylene glycol dimethyl ether, or a combination of at least two thereof.

[0051] Further preferably, the solvent is selected from any one or a combination of at least two of toluene, xylene or cyclohexane.

[0052] Preferably, the amount of the solvent used in step (2) is 1.0 to 10.0 times the weight of o-trifluoromethylbenzoyl chloride; for example, 1.0, 2.0, 3.0, 5.0, 8.0 or 10.0 times

[0053] Preferably, the solvent type used in step (1) and step (2) is the same, and preferably the solvent is toluene.

[0054] Preferably, the addition mode of o-trifluoromethylbenzoyl chloride in step (2) is dropwise addition, and the dropwise addition time is 0.1 to 20.0 h (e.g., 0.1 h, 0.5 h, 1.0 h, 2.0 h, 5.0 h, 8.0 h, 10.0 h, 13.0 h, 15.0 h, 18.0 h or 20.0 h), preferably 2.0 to 8.0 h. The time for continuing the reaction after the dropwise addition is preferably 0.1 to 5 h (e.g., 0.1 h, 0.5 h, 1.0 h, 2.0 h, 3.0 h or 5.0 h); more preferably 0.5 to 3 h.

[0055] As a preferred technical solution of the present invention, the synthesis method of fluopyram specifically comprises the following steps:

[0056] (1) In the presence of a catalyst, o-trifluoromethylbenzoic acid and solid phosgene are reacted in a solvent at a molar ratio of 1:1.0-10.0 at -5-120°C for 1-10 hours to obtain o-trifluoromethylbenzoyl chloride; the catalyst is any one of a pyridine compound, a dialkylamide compound or a tertiary amine compound, or a combination of at least two thereof, and the amount of the catalyst is 0.001-1.0 times the molar amount of o-trifluoromethylbenzoic acid; the solvent of the reaction is any one of an aromatic hydrocarbon solvent, a chlorinated alkane solvent, an alkane solvent or an ether solvent, or a combination of at least two thereof, and the amount of the solvent is 1.0-10.0 times the weight of the solid phosgene;

[0057] (2) adding o-trifluoromethylbenzoyl chloride dropwise to a solvent containing 3-chloro-2-aminoethyl-5-trifluoromethylpyridine or its hydrochloride within 0.1 to 20.0 hours, and reacting directly at 30 to 200° C. for 0.1 to 5 hours after the addition is completed, to obtain the target product fluopyram, wherein the molar ratio of o-trifluoromethylbenzoyl chloride to 3-chloro-2-aminoethyl-5-trifluoromethylpyridine or its hydrochloride is 1:1.0 to 1.50, and the solvent is selected from any one of an aromatic hydrocarbon solvent, a chlorinated alkane solvent, an alkane solvent or an ether solvent, or a combination of at least two thereof, and the amount of the solvent used is 1.0 to 10.0 times the weight of the o-trifluoromethylbenzoyl chloride.

[0058] In the present invention, in order to solve the problems existing in the synthesis of fluopyram, the method for preparing formula I and fluopyram of the present invention uses o-trifluoromethylbenzoic acid as a raw material, and prepares an acyl chloride via solid phosgene. The obtained acyl chloride solution does not need further separation and purification, and can be directly reacted with formula I or formula II to prepare fluopyram without using an acid binding agent.

[0059] The present invention adopts solid phosgene as a chlorinating agent to prepare o-trifluoromethylbenzoyl chloride, adopts pyridine and DMF as two components for catalysis, and the yield is as high as 98% or more; solid phosgene is used to replace thionyl chloride in the present invention, and the tail gas after the reaction is only hydrogen chloride and carbon dioxide, thereby avoiding the problem of handling sulfur-containing waste gas; in the present invention, step (2) avoids the use of an acid binding agent, and the product can be obtained by removing the solvent after the reaction is completed, and the treatment process is simpler; compared with the acid binding agent method, the scheme also avoids the generation of saline waste water. In the present invention, the two-step reaction of step (1) and step (2) can be coupled by adopting the same solvent, which is more conducive to industrial production.

[0060] Compared with the prior art, the present invention has the following beneficial effects:

[0061] In the preparation method of the present invention, step (1) uses solid phosgene as a raw material, and the by-products are hydrogen chloride and carbon dioxide. In a small test, the tail gas is treated by absorbing alkaline liquid. In industry, an absorption tower is generally used to recover hydrogen chloride as 31% industrial hydrochloric acid. In step (2), no acid binding agent is used, and the amount of liquid alkali per ton of fluopyram can be reduced by 32%, about 600 kg, and the raw material cost is saved by about 550 yuan. In step (2), the introduction of water and salt is avoided, and the target product can be obtained by cooling and crystallizing after the reaction is completed. The process is simpler and easy to operate, and the yield of the preparation method of the present invention reaches more than 98%. BRIEF DESCRIPTION OF THE DRAWINGS

[0062] Figure 1 This is the gas phase normalization diagram of the product prepared in Example 1.

[0063] Figure 2 This is the liquid phase normalization diagram of the product prepared in Example 9. DETAILED DESCRIPTION

[0064] The technical solution of the present invention is further described below by specific implementation methods. It should be understood by those skilled in the art that the embodiments are only to help understand the present invention and should not be regarded as specific limitations of the present invention.

[0065] The implementation conditions used in the examples can be further adjusted according to specific requirements. The implementation conditions not specified are usually the conditions in conventional tests. The contents described below are all mass contents.

[0066] Example 1

[0067] 47.5g (99.0%, 0.25mol) o-trifluoromethylbenzoic acid, 50.0g toluene, 0.18g (2.5mmol) DMF and 0.20g (2.5mmol) pyridine were added to a 500mL four-necked reaction bottle equipped with a stirrer, a thermometer and a condenser tube. 166.0g toluene solution of Guguang (containing 26.0g, 0.26mol, 1.05eq of Guguang) was added dropwise at about 60°C. The tail gas of the reaction bottle was absorbed by a saturated sodium bicarbonate solution. The addition was completed in about 6 hours. After the addition was completed, the reaction was continued for 1 hour. The reaction solution was distilled by a water pump under reduced pressure (about 25mmHg). The 98-100°C fraction was collected to obtain 52.3g o-trifluoromethylbenzoyl chloride (quantitative content 98.0%, yield 98.3%).

[0068] Product GC (Shimadzu GC-2014 gas chromatograph, FID hydrogen flame ionization detector, automatic sampler AOC-20i (micro syringe: 10 μL), GC-Soulution chromatography workstation; gas chromatography column: RTX-5 (0.50um×0.32mm ID×30m) capillary column;) normalized graph as shown Figure 1 shown.

[0069] 1 H NMR (400MHz, CDCl3), δppm: 8.036~8.018 (dd, J=3.8, 3Hz, 2H, CH), 7.817~7.794 (dd, J=5.6, 3.6Hz, 2H, CH).

[0070] Examples 2 to 7 were implemented with reference to Example 1, except for the type and amount of catalyst used. The specific results are shown in Table 1 below:

[0071] Table 1

[0072]

[0073] Example 8

[0074] 12.4g (99.0%, 47.1mmol) of 2-(3-chloro-5-(trifluoromethyl)pyridin-2-yl)ethylamine hydrochloride and 40.0g of toluene were added into a four-necked bottle with a thermometer and mechanical stirring, stirred thoroughly, and heated to about 110°C in an oil bath. Then, 11.0g (51.8mmol, 1.1eq) of o-trifluoromethylbenzoyl chloride was slowly dripped into the system under nitrogen protection, and the tail gas of the reaction bottle was absorbed by a saturated sodium bicarbonate solution. After dripping, the reaction was kept warm for about 30 minutes. HPLC tracking showed that the remaining 2-(3-chloro-5-(trifluoromethyl)pyridin-2-yl)ethylamine hydrochloride was less than 0.5%. The reaction was stopped and the solvent was distilled off under reduced pressure to obtain 18.5 g of a light yellow solid. Liquid chromatography external standard quantitative analysis showed that the solid contained 96.0% of fluopyram and the yield was 95.0% based on 2-(3-chloro-5-(trifluoromethyl)pyridin-2-yl)ethanamine hydrochloride.

[0075] The product liquid phase (instrument: Shimadzu LC-20AT high performance liquid chromatograph, SPD-M20A diode array detector, LabSolution chromatography workstation; chromatographic column: ZORBAX SB-C18, 4.6 mm × 150 mm × 5 μm;) normalized graph is shown in Figure 2 shown.

[0076] NMR data:

[0077] 1 H NMR (500MHz, DMSO-d6): δppm, 3.22~3.25(t,2H), 3.67~3.72(m,2H), 7.48~7.51 (m,1H),7.62(t,1H),7.69~7.76(m,2H),8.43(s,1H),8.58(s,1H),8.90(s,1H).

[0078] Example 9

[0079] 10.6g (98.0%, 46.2mmol) 2-(3-chloro-5-(trifluoromethyl)pyridin-2-yl)ethylamine and 30.0g toluene were added into a four-necked bottle with a thermometer and mechanical stirring, stirred thoroughly, and heated to about 110°C in an oil bath. Then, 10.8g (98.0%, 50.8mmol, 1.1eq) o-trifluoromethylbenzoyl chloride was slowly dripped into the system under nitrogen protection, and the tail gas of the reaction bottle was connected to a saturated sodium bicarbonate solution for absorption. After dripping, the reaction was kept warm for about 30 minutes. HPLC tracking was stopped when the remaining 2-(3-chloro-5-(trifluoromethyl)pyridin-2-yl)ethylamine was less than 0.5%. After the reaction, the solvent was evaporated under reduced pressure to obtain 18.3 g of a light yellow solid, which contained 96.1% (44.3 mmol) of fluopyram by external standard and a yield of 95.9% based on 2-(3-chloro-5-(trifluoromethyl)pyridin-2-yl)ethanamine.

[0080] Examples 10 to 15 were implemented with reference to Example 8, except that the solvent used, the reaction temperature, and the molar ratio of 2-(3-chloro-5-(trifluoromethyl)pyridin-2-yl)ethylamine hydrochloride and o-trifluoromethylbenzoyl chloride were as shown in Table 2.

[0081] Table 2

[0082]

[0083] It can be seen from the above experimental results that the preparation method of the present invention has a high yield, wherein step 1 uses pyridine and DMF as two components for catalysis, and the yield is more than 98%; step 2 uses toluene as solvent, and the yield is more than 95%.

[0084] In the preparation method of the present invention, solid light is used to replace thionyl chloride, and the tail gas after the reaction is only hydrogen chloride and carbon dioxide, which avoids the problem of handling sulfur-containing waste gas and the use of acid-binding agents. The product can be obtained by removing the solvent after the reaction is completed, and the treatment process is simpler; compared with the acid-binding agent method, this scheme also avoids the generation of salt-containing wastewater. The two-step reaction can be coupled by using the same solvent, which is more conducive to industrial production.

[0085] The applicant declares that the present invention illustrates the synthesis method of fluopyram of the present invention through the above-mentioned embodiments, but the present invention is not limited to the above-mentioned embodiments, that is, it does not mean that the present invention must rely on the above-mentioned embodiments to be implemented. Those skilled in the art should understand that any improvement of the present invention, equivalent replacement of various raw materials of the product of the present invention, addition of auxiliary components, selection of specific methods, etc., all fall within the protection scope and disclosure scope of the present invention.

Claims

1. A method for synthesizing fluopyram, characterized in that: The method comprises the following steps: (1) In the presence of a catalyst, o-trifluoromethylbenzoic acid reacts with solid phosgene in a solvent to obtain o-trifluoromethylbenzoyl chloride; (2) o-Trifluoromethylbenzoyl chloride is directly reacted with 3-chloro-2-aminoethyl-5-trifluoromethylpyridine or its hydrochloride in a solvent to obtain the target product fluopyram.

2. The method for synthesizing fluopyram according to claim 1, characterized in that: The catalyst in step (1) is any one of a pyridine compound, a dialkylamide compound or a tertiary amine compound, or a combination of at least two thereof; Preferably, the pyridine compound is selected from pyridine and / or 4-dimethylaminopyridine; Preferably, the dialkylamide compound is selected from N,N-dimethylformamide and / or N,N-methylacetamide; Preferably, the tertiary amine compound is selected from any one or a combination of at least two of triethylamine, trimethylamine or N,N-dimethylaniline; Preferably, the amount of the catalyst used is 0.001-1.0 times the molar amount of o-trifluoromethylbenzoic acid.

3. The method for synthesizing fluopyram according to claim 1 or 2, characterized in that: The catalyst is a combination of pyridine and N,N-dimethylformamide, wherein the amount of pyridine is 0.001-0.5 times the molar amount of o-trifluoromethylbenzoic acid, and the amount of N,N-dimethylformamide is 0.001-0.5 times the molar amount of o-trifluoromethylbenzoic acid; The molar ratio of o-trifluoromethylbenzoic acid to solid phosgene in step (1) is 1:1.0 to 10.0; more preferably 1:1.0 to 3.0; Preferably, the solvent for the reaction in step (1) is selected from any one or a combination of at least two of an aromatic hydrocarbon solvent, a chlorinated alkane solvent, an alkane solvent or an ether solvent; Preferably, the aromatic hydrocarbon solvent is selected from any one or a combination of at least two of toluene, xylene or chlorobenzene; Preferably, the chlorinated alkane solvent is selected from any one or a combination of at least two of 1,2-dichloroethane, chloroform or carbon tetrachloride; Preferably, the alkane solvent is selected from any one or a combination of at least two of pentane, hexane, methylcyclohexane, heptane, cyclopentane, cyclohexane or cycloheptane; Preferably, the ether solvent is selected from any one or a combination of at least two of diethyl ether, tetrahydrofuran or ethylene glycol dimethyl ether; Further preferably, the solvent is selected from any one or a combination of at least two of toluene, xylene, 1,2-dichloroethane, cyclohexane or methylcyclohexane.

4. The method for synthesizing fluopyram according to any one of claims 1 to 3, characterized in that: The amount of the solvent used in step (1) is 1.0 to 10.0 times the weight of the solid phosgene; preferably, the amount of the solvent used is just enough to completely dissolve the solid phosgene required for the feed; Preferably, the solid phosgene is added in step (1) by directly adding the solid or by adding dropwise after dissolving the solid.

5. The method for synthesizing fluopyram according to any one of claims 1 to 4, characterized in that: The specific implementation method of step (1) is as follows: o-trifluoromethylbenzoic acid, a catalyst and an appropriate amount of solvent are placed in a reactor and stirred evenly; after the reaction temperature is well controlled, solid phosgene is slowly added to the fully stirred reaction system through a solid feeder to react; Preferably, the reaction temperature in step (1) is -5 to 120°C; more preferably 30 to 100°C; Preferably, the reaction time in step (1) is 1 to 10 hours.

6. The method for synthesizing fluopyram according to any one of claims 1 to 5, characterized in that: In step (2), the molar ratio of o-trifluoromethylbenzoyl chloride to 3-chloro-2-aminoethyl-5-trifluoromethylpyridine or its hydrochloride is 1:1.0-1.50; Preferably, the reaction temperature in step (2) is 30 to 200°C, preferably 60 to 150°C.

7. The method for synthesizing fluopyram according to any one of claims 1 to 6, characterized in that: The solvent for the reaction in step (2) is selected from any one of aromatic hydrocarbon solvents, chlorinated alkane solvents, alkane solvents or ether solvents, or a combination of at least two thereof; Preferably, the aromatic hydrocarbon solvent is selected from any one or a combination of at least two of toluene, xylene or chlorobenzene; Preferably, the chlorinated alkane solvent is selected from any one or a combination of at least two of 1,2-dichloroethane, chloroform or carbon tetrachloride; Preferably, the alkane solvent is selected from any one or a combination of at least two of pentane, hexane, heptane, cyclopentane, cyclohexane or cycloheptane; Preferably, the ether solvent is selected from any one or a combination of at least two of diethyl ether, tetrahydrofuran or ethylene glycol dimethyl ether; Further preferably, the solvent is selected from any one or a combination of at least two of toluene, xylene or cyclohexane.

8. The method for synthesizing fluopyram according to any one of claims 1 to 7, characterized in that: The amount of the solvent used in step (2) is 1.0 to 10.0 times the weight of o-trifluoromethylbenzoyl chloride; Preferably, the solvent type used in step (1) and step (2) is the same, and preferably, the solvent used in step (1) and step (2) is toluene.

9. The method for synthesizing fluopyram according to any one of claims 1 to 8, characterized in that: In step (2), the addition method of o-trifluoromethylbenzoyl chloride is dropwise addition, and the dropwise addition time is 0.1 to 20.0 hours, preferably 2.0 to 8.0 hours. The time for continuing the reaction after the dropwise addition is preferably 0.1 to 5 hours; more preferably 0.5 to 3 hours.

10. The method for synthesizing fluopyram according to any one of claims 1 to 9, characterized in that: The synthesis method of fluopyram specifically comprises the following steps: (1) In the presence of a catalyst, o-trifluoromethylbenzoic acid and solid phosgene are reacted in a solvent at a molar ratio of 1:1.0-10.0 at -5-120°C for 1-10 hours to obtain o-trifluoromethylbenzoyl chloride; the catalyst is any one of a pyridine compound, a dialkylamide compound or a tertiary amine compound, or a combination of at least two thereof, and the amount of the catalyst is 0.001-1.0 times the molar amount of o-trifluoromethylbenzoic acid; the solvent of the reaction is selected from any one of an aromatic hydrocarbon solvent, a chlorinated alkane solvent, an alkane solvent or an ether solvent, or a combination of at least two thereof, and the amount of the solvent is 1.0-10.0 times the weight of the solid phosgene; (2) adding o-trifluoromethylbenzoyl chloride dropwise to a solvent containing 3-chloro-2-aminoethyl-5-trifluoromethylpyridine or its hydrochloride within 0.1 to 20.0 hours, and reacting directly at 30 to 200° C. for 0.1 to 5 hours after the addition is completed, to obtain the target product fluopyram, wherein the molar ratio of o-trifluoromethylbenzoyl chloride to 3-chloro-2-aminoethyl-5-trifluoromethylpyridine or its hydrochloride is 1:1.0 to 1.50, and the solvent is selected from any one of an aromatic hydrocarbon solvent, a chlorinated alkane solvent, an alkane solvent or an ether solvent, or a combination of at least two thereof, and the amount of the solvent used is 1.0 to 10.0 times the weight of the o-trifluoromethylbenzoyl chloride.

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