A kind of preparation method of nitrobenzamide

Abstract

The invention provides a preparation method of nitrobenzamide, and the preparation method comprises the following steps: reacting 2-chloro-3-nitrobenzoic acid with a chlorinating agent to obtain 2-chloro-3-nitrobenzoyl chloride; reacting 2-chloro-3-nitrobenzoyl chloride with a fluorinating agent to obtain 2-fluoro-3-nitrobenzoyl fluoride; and then condensing with 4-(perfluoropropane-2-yl)-2-(trifluoromethyl)aniline to obtain 2-fluoro-3-nitro-N-(4-(perfluoropropane-2-yl)-2-(trifluoromethyl)phenyl)benzamide. The preparation method provided by the invention has simple operation steps, low cost, high yield, high purity, and is suitable for industrial production.

Description

Technical Field

[0001] The invention belongs to the technical field of chemical synthesis and relates to a preparation method of nitrobenzamide, in particular to a preparation method of 2-fluoro-3-nitro-N-(4-(perfluoropropane-2-yl)-2-(trifluoromethyl)phenyl)benzamide. Background Art

[0002] 2-Fluoro-3-nitro-N-(4-(perfluoropropane-2-yl)-2-(trifluoromethyl)phenyl)benzamide (as shown in Formula I, referred to as nitroamide in the present invention) is an important pesticide intermediate, which is used in the synthesis of novel and highly effective diamide insecticides, cyprodinil and bromofenac. These two insecticides are not currently produced on a large scale in the international and domestic markets. The main reason for this is that the current preparation process cost is too high, which seriously restricts the marketization process of these two insecticides.

[0003] CN112707836A discloses the preparation of the nitroamide using 2-fluoro-3-nitrobenzoic acid (as shown in Formula II) as a raw material, but the synthesis method of 2-fluoro-3-nitrobenzoic acid is rarely reported. The method first prepares 2-fluoro-3-nitrobenzoyl chloride, and then undergoes a condensation reaction with 4-(perfluoropropane-2-yl)-2-(trifluoromethyl)aniline (as shown in Formula III, referred to as decafluoroaniline in the present invention) to obtain 2-fluoro-3-nitro-N-(4-(perfluoropropane-2-yl)-2-(trifluoromethyl)phenyl)benzamide, and the preparation reaction formula is as follows:

[0004]

[0005] CN101177400A discloses that o-fluorotoluene is used as a raw material, and a mixture of 2-fluoro-3-nitrotoluene and 2-fluoro-5-nitrotoluene is obtained after nitration, and 2-fluoro-3-nitrotoluene is obtained after distillation. 2-fluoro-3-nitrotoluene can be oxidized to obtain 2-fluoro-3-nitrobenzoic acid, but the two-step yield is only 15%, which makes it unsuitable for industrial production of 2-fluoro-3-nitrobenzoic acid. The reaction route is as follows:

[0006]

[0007] CN113024384A reported that 2-fluoro-3-nitrobenzoic acid was obtained by nitration, chlorination, fluorination and oxidation of o-methylphenol, with a total yield of 41%. The fluorination reaction used expensive cesium fluoride as a fluorination reagent, which is costly and not suitable for industrial production. The preparation reaction formula is as follows:

[0008]

[0009] In summary, due to the high price of 2-fluoro-3-nitrobenzoic acid (5,000 yuan / kg) and the fact that the currently reported synthesis method is not suitable for industrial production, the cost of producing nitroamide using 2-fluoro-3-nitrobenzoic acid as raw material is as high as 2,615 yuan / kg, which is difficult to produce on a large scale.

[0010] In summary, since nitroamide is an important chemical intermediate, but currently 2-fluoro-3-nitrobenzoic acid is expensive and there is no effective production method suitable for industrialization, therefore, how to provide a preparation method suitable for industrial production of nitroamide has become an urgent problem to be solved. Summary of the invention

[0011] In view of the deficiencies of the prior art, the object of the present invention is to provide a method for preparing nitrobenzamide, a method for preparing 2-fluoro-3-nitro-N-(4-(perfluoropropane-2-yl)-2-(trifluoromethyl)phenyl)benzamide (referred to as nitrobenzamide or nitroamide). The preparation method provided by the present invention has simple operation steps, low cost, high yield, high purity, and is suitable for industrial production.

[0012] To achieve this object, the present invention adopts the following technical solutions:

[0013] In one aspect, the present invention provides a method for preparing 2-fluoro-3-nitro-N-(4-(perfluoropropane-2-yl)-2-(trifluoromethyl)phenyl)benzamide, the preparation method comprising the following steps:

[0014] (1) 2-chloro-3-nitrobenzoic acid is reacted with a chlorinating agent to obtain 2-chloro-3-nitrobenzoyl chloride, and the reaction formula is as follows:

[0015]

[0016] (2) The 2-chloro-3-nitrobenzoyl chloride obtained in step (1) reacts with a fluorinating agent to obtain 2-fluoro-3-nitrobenzoyl fluoride, and the reaction formula is as follows:

[0017]

[0018] (3) condensing the 2-fluoro-3-nitrobenzoyl fluoride obtained in step (2) with 4-(perfluoropropane-2-yl)-2-(trifluoromethyl)aniline to obtain the 2-fluoro-3-nitro-N-(4-(perfluoropropane-2-yl)-2-(trifluoromethyl)phenyl)benzamide, wherein the preparation reaction formula is as follows:

[0019]

[0020] The present invention no longer uses 2-fluoro-3-nitrobenzoic acid, a raw material which is expensive and has no synthetic route suitable for industrial mass production, but uses 2-chloro-3-nitrobenzoic acid as a raw material. The raw material can be purchased, or a chemical synthesis method can be used to prepare a large amount of raw materials which are cheap and can be purchased commercially in large quantities, so as to reduce the cost. Unlike 2-fluoro-3-nitrobenzoic acid which is expensive, industrial preparation is not easy to achieve, and there is no existing process route suitable for industrial preparation. The present invention uses the above-mentioned preparation method to obtain a nitroamide product through acyl chlorination reaction, fluorination, and condensation. The operation steps are simple, the cost is as low as 1,200 yuan / kg, and the obtained nitroamide has a high yield and high purity.

[0021] In the present invention, 2-chloro-3-nitrobenzoic acid is used as a raw material to prepare nitroamide, and the yield is 67%-85%. The synthesis yield of 2-chloro-3-nitrobenzoic acid raw material can reach about 94%. Therefore, if the cost and yield of the raw material are taken into account, the present invention can reduce the cost while ensuring a high yield of the product, which can meet the needs of industrialization. While using 2-fluoro-3-nitrobenzoic acid as a raw material, although the yield of the product obtained by using 2-fluoro-3-nitrobenzoic acid as a raw material may be higher, on the one hand, it cannot be purchased in large quantities commercially; on the other hand, the preparation yield of 2-fluoro-3-nitrobenzoic acid is only 15%-41% according to the prior art reports, so if the acquisition of the raw material is taken into account, its overall total yield is only 14%-39%; therefore, from this aspect, the present invention reduces the cost while maintaining a higher preparation yield of the target product, i.e., nitroamide, and is more suitable for industrial production.

[0022] Preferably, the chlorination reagent in step (1) is one or a combination of at least two of thionyl chloride, triphosgene, oxalyl chloride, phosphorus trichloride or phosphorus pentachloride, preferably thionyl chloride or triphosgene.

[0023] Preferably, the molar ratio of 2-chloro-3-nitrobenzoic acid to the chlorination agent in step (1) is 1:(0.35-2.5), preferably 1:(0.5-2.0).

[0024] Preferably, the solvent for the reaction in step (1) is any one of tetrahydrofuran, dichloromethane, 1,2-dichloroethane, chloroform, benzene, toluene, xylene, chlorobenzene or dichlorobenzene, or a combination of at least two thereof, preferably toluene and / or xylene.

[0025] Preferably, the reaction temperature in step (1) is 40-180°C, for example 40°C, 45°C, 50°C, 70°C, 80°C, 100°C, 110°C, 120°C, 130°C, 140°C, 150°C, 170°C or 180°C, preferably 110-140°C.

[0026] Preferably, the reaction time of step (1) is 1 to 8 h, such as 1 h, 3 h, 5 h, 6 h or 8 h, preferably 2 to 6 h.

[0027] In the present invention, the 2-chloro-3-nitrobenzoic acid can be obtained by synthesis, and the specific synthesis method comprises the following steps:

[0028] (I) mixing 2-amino-3-nitrobenzoic acid alkali metal salt with nitrite and hydrochloric acid to obtain a first reaction solution;

[0029] (II) mixing the first reaction solution obtained in step (I) with hydrochloric acid and a catalyst to react to obtain the 2-chloro-3-nitrobenzoic acid.

[0030] In the preparation method of 2-chloro-3-nitrobenzoic acid of the present invention, the nitrite includes sodium nitrite, the mass fraction of the hydrochloric acid is 10 to 36.5%, and the catalyst includes copper and / or cuprous chloride.

[0031] In the preparation method of 2-chloro-3-nitrobenzoic acid of the present invention, the molar ratio of 2-amino-3-nitrobenzoic acid alkali metal salt to nitrite in step (I) is 1:(1-1.5), and the molar ratio of 2-amino-3-nitrobenzoic acid alkali metal salt to acid is 1:(5-40); the reaction temperature in step (I) is -10-25°C, and the reaction time is 0.5-2h.

[0032] In the preparation method of 2-chloro-3-nitrobenzoic acid of the present invention, the molar ratio of the catalyst in step (II) to the alkali metal salt of 2-amino-3-nitrobenzoic acid in step (I) is (0.05-1):1; the molar ratio of the hydrogen chloride in the hydrochloric acid to the alkali metal salt of 2-amino-3-nitrobenzoic acid in step (I) is (5-20):1, and the reaction in step (II) is carried out at -10-25°C for 1-3h, and then kept warm at -5-5°C for 0.5-1h.

[0033] Preferably, the fluorination agent in step (2) is potassium fluoride and / or cesium fluoride, preferably potassium fluoride.

[0034] Preferably, the molar ratio of 2-chloro-3-nitrobenzoyl chloride to the fluorination agent in step (2) is 1:(2.0-5.0), for example 1:2.0, 1:2.5, 1:3.0, 1:3.5, 1:4.0, 1:4.5, 1:5.0, preferably 1:(3.0-3.5).

[0035] Preferably, the phase transfer catalyst in step (2) is at least one of 18-crown-6, tetramethylammonium chloride, tetramethylammonium bromide, tetrabutylammonium bromide, hexadecyltrimethylammonium chloride, nonylphenol polyoxyethylene ether or tetraphenylphosphine bromide, preferably 18-crown-6 and / or tetramethylammonium chloride.

[0036] Preferably, the reaction in step (2) is carried out in the presence of a phase transfer catalyst.

[0037] Preferably, the mass ratio of the 2-chloro-3-nitrobenzoic acid to the phase transfer catalyst in step (2) is 1:(0% to 5.0%). For example, 1:0.5%, 1:1.0%, 1:1.5%, 1:2.0%, 1:2.5%, 1:3.0%, 1:3.5%, 1:4.0%, 1:4.5%, 1:5.0%, preferably 1:(1.0%-1.5%).

[0038] Preferably, the solvent for the reaction in step (2) is any one of benzene, toluene, xylene, chlorobenzene, nitrobenzene, tetrahydrofuran, 2-methyltetrahydrofuran, acetonitrile, propionitrile, butyronitrile, N,N-dimethylformamide, N,N-dimethylacetamide, N-methylpyrrolidone, dimethyl sulfoxide or cyclopentane sulfone, or a combination of at least two thereof, preferably toluene and / or xylene.

[0039] Preferably, the mass ratio of the 2-chloro-3-nitrobenzoic acid to the solvent in step (2) is 1:(0.5-4.0), for example 1:0.5, 1:1.0, 1:1.5, 1:2.0, 1:2.5, 1:3.0, 1:3.5, 1:4.0, preferably 1:(0.5-1.0).

[0040] Preferably, the reaction temperature in step (2) is 60-180°C, for example, it can be 60°C, 70°C, 80°C, 90°C, 100°C, 110°C, 120°C, 130°C, 140°C, 150°C, 160°C, 170°C, 180°C, etc., but is not limited to the values ​​listed above. Other values ​​not listed within the above numerical range are also applicable, preferably 80-120°C.

[0041] Preferably, the reaction time of step (2) is 0.5 to 80 h, for example, it can be 0.5 h, 2 h, 4 h, 8 h, 10 h, 12 h, 14 h, 16 h, 18 h, 20 h, 24 h, 28 h, 32 h, 36 h, 40 h, 45 h, 50 h, 55 h, 60 h, 65 h, 70 h, 75 h or 80 h, but is not limited to the values ​​listed above, and other values ​​not listed within the above numerical range are also applicable.

[0042] In the present invention, after the reaction in step (2) is completed, the reaction solution is filtered, and the filtrate is desolventized and then distilled under reduced pressure to obtain the 2-fluoro-3-nitrobenzoyl fluoride.

[0043] Preferably, the desolventizing of the filtrate is to remove the solvent by distilling the filtrate under reduced pressure at a pressure of 2 KPa-5 KPa (e.g., 2 KPa, 2.5 KPa, 3 KPa, 3.5 KPa, 4 KPa, 4.5 KPa or 5 KPa).

[0044] Optionally, the pressure of the reduced pressure distillation after desolventizing is 20Pa-500Pa, for example, 20Pa, 50Pa, 100Pa, 150Pa, 200Pa, 250Pa, 300Pa, 350Pa, 400Pa, 450Pa or 500Pa.

[0045] Preferably, the molar ratio of 2-fluoro-3-nitrobenzoyl fluoride to 4-(perfluoropropane-2-yl)-2-(trifluoromethyl)aniline in step (3) is (1-1.5):1, for example, 1:1, 1.1:1, 1.2:1, 1.3:1, 1.4:1 or 1.5:1, preferably (1.1-1.3):1.

[0046] Preferably, the solvent for the reaction in step (3) is any one of dichloromethane, 1,2-dichloroethane, chloroform, benzene, toluene, xylene, chlorobenzene, dichlorobenzene or sulfolane, or a combination of at least two thereof, preferably toluene and / or xylene.

[0047] Preferably, the mass ratio of the 4-(perfluoropropane-2-yl)-2-(trifluoromethyl)aniline to the solvent in step (3) is 1:(1-5), for example 1:1, 1:1.2, 1:1.5, 1:1.8, 1:2, 1:2.2, 1:2.4, 1:2.5, 1:2.7, 1:2.8, 1:2.9, 1:3, 1:3.2, 1:3.4, 1:3.6, 1:3.8, 1:4, 1:4.3, 1:4.5, 1:4.8 or 1:5, preferably 1:(2-4).

[0048] Preferably, the reaction in step (3) is carried out in the presence of a catalyst, and the catalyst is 4-dimethylaminopyridine (DMAP).

[0049] Preferably, the amount of the catalyst is 0.1%-5% of the mass of 4-(perfluoropropane-2-yl)-2-(trifluoromethyl)aniline, for example, 0.1%, 0.3%, 0.5%, 0.8%, 1%, 1.5%, 1.8%, 2%, 2.3%, 2.5%, 2.8%, 3%, 3.5%, 3.8%, 4%, 4.5% or 5%, etc.

[0050] Preferably, the temperature of the condensation reaction in step (3) is 40-180°C, for example 40°C, 50°C, 60°C, 80°C, 100°C, 120°C, 140°C, 150°C, 170°C or 180°C, preferably 110-140°C.

[0051] Preferably, the condensation reaction time in step (3) is 3 to 8 h, for example, 3 h, 3.3 h, 3.5 h, 3.8 h, 4 h, 4.5 h, 4.8 h, 5 h, 5.3 h, 5.5 h, 5.8 h, 6 h, 6.5 h, 6.8 h, 7 h, 7.5 h, 7.8 h or 8 h, preferably 4 to 6 h.

[0052] Preferably, after the condensation reaction in step (3) is completed, post-treatment is carried out, and the post-treatment comprises the following steps: adding alkali solution to the reaction system, stirring at 35°C-80°C for 10-40min (for example, 10min, 15min, 18min, 20min, 23min, 25min, 28min, 30min, 35min or 40min), separating the liquid while hot, cooling the obtained organic layer to room temperature, and then placing it at 0-5°C (for example, 0°C, 1°C, 2°C, 3°C, 4°C or 5°C) and stirring for 1-3h (for example, 1h, 1.3h, 1.5h, 1.8h, 2h, 2.3h, 2.5h, 2.8h or 3h), filtering and drying to obtain 2-fluoro-3-nitro-N-(4-(perfluoropropane-2-yl)-2-(trifluoromethyl)phenyl)benzamide.

[0053] In the post-treatment after the condensation reaction in step (3) of the present invention is completed, the stirring temperature after adding the alkali solution should be maintained at 35°C-80°C. If the temperature is too low, it will cause precipitation of the material, and if the temperature is too high, side reactions will occur.

[0054] Preferably, the alkali solution is one or a combination of at least two of an aqueous solution of a hydroxide, carbonate or bicarbonate of an alkali metal or alkaline earth metal, preferably a sodium hydroxide solution or a sodium carbonate solution.

[0055] As a preferred technical solution of the present invention, the preparation method of 2-fluoro-3-nitro-N-(4-(perfluoropropane-2-yl)-2-(trifluoromethyl)phenyl)benzamide specifically comprises the following steps:

[0056] (1) reacting 2-chloro-3-nitrobenzoic acid with a chlorinating agent at a molar ratio of 1:(0.35-2.5) at 40-180° C. for 1-8 hours to obtain 2-chloro-3-nitrobenzoyl chloride;

[0057] (2) The 2-chloro-3-nitrobenzoyl chloride obtained in step (1) and a fluorinating agent are reacted at a molar ratio of 1:(2.0-5.0) at 60-180° C. for 0.5-80 h. After the reaction is completed, the reaction solution is filtered, and the filtrate is desolventized and distilled under reduced pressure to obtain 2-fluoro-3-nitrobenzoyl fluoride;

[0058] (3) condensing the 2-fluoro-3-nitrobenzoyl fluoride obtained in step (2) with 4-(perfluoropropane-2-yl)-2-(trifluoromethyl)aniline at a molar ratio of (1 to 1.5):1 and a temperature of 40 to 180° C. for 3 to 8 hours to obtain the 2-fluoro-3-nitro-N-(4-(perfluoropropane-2-yl)-2-(trifluoromethyl)phenyl)benzamide.

[0059] Compared with the prior art, the present invention has the following beneficial effects:

[0060] The present invention adopts 2-chloro-3-nitrobenzoic acid as a raw material, prepares 2-fluoro-3-nitrobenzoyl fluoride through chlorination and fluorination, and then condenses with 4-(perfluoropropane-2-yl)-2-(trifluoromethyl)aniline to obtain nitroamide, and the process is simple to operate, the cost is as low as 1200 yuan / kg, the yield is high, the purity is high, and the process is suitable for industrial production. The raw material 2-chloro-3-nitrobenzoic acid is easily prepared in large quantities from a raw material that is cheap and commercially available in large quantities, which avoids using 2-fluoro-3-nitrobenzoic acid that is expensive, difficult to commercially purchase in large quantities, and difficult to prepare at a reasonable cost and with an acceptable yield as a raw material, and the product can also be obtained in high yield. DETAILED DESCRIPTION

[0061] 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.

[0062] In the following examples, the purity test method is liquid chromatography, the chromatographic column specification is Shimadzu Shim-pack GISTC18 (5μm), 4.6ID×150mm stainless steel column. The quantitative method is the external standard method.

[0063] In the present invention, the raw material 4-(perfluoropropane-2-yl)-2-(trifluoromethyl)aniline (i.e., decafluoroaniline) is prepared by a preparation method of the prior art, for example, by a method disclosed in EP2319830A1, and the specific preparation method is as follows: 100 g (0.608 mol) of 2-(trifluoromethyl)aniline, 131 g (0.639 mol) of 85% sodium dithionite and 20.9 g (0.0608 mol) of tetrabutylammonium hydrogen sulfate are added to a mixed solution of 1500 mL of ethyl acetate and 1500 mL of water, and then 53.9 g (0.639 mol) of sodium bicarbonate are added. 198 g (0.669 mol) of heptafluoroisopropyl iodide is added dropwise thereto at room temperature, and the mixture is separated after stirring at room temperature for 6 hours, the solvent of the organic layer is evaporated under reduced pressure, and 500 mL of ethyl acetate is added thereto. Then 160 g (0.608 mol) of 4M hydrogen chloride / ethyl acetate solution was added dropwise, stirred at room temperature for 30 minutes and then at 5°C for 1 hour. The mixture was filtered, and the filtrate was washed with water and saturated sodium bicarbonate aqueous solution in turn, then dried over anhydrous magnesium sulfate, and the solvent was evaporated under reduced pressure. The obtained residue was purified by silica gel column chromatography (elution solvent: hexane: ethyl acetate = 10: 1) to obtain 60.0 g (yield 30%) of 4-(perfluoropropane-2-yl)-2-(trifluoromethyl)aniline.

[0064] In the present invention, the preparation method of the raw material 2-chloro-3-nitrobenzoic acid is as follows:

[0065] (1) Add 219 g (1.2 mol, 20%) hydrochloric acid to a 1000 mL four-necked bottle, control the reaction temperature to 5° C., and simultaneously dropwise add 102.1 g (0.08 mol, 16%) 2-amino-3-nitrobenzoic acid sodium salt solution (obtained by hydrolyzing 2-amino-3-nitrobenzoic acid methyl ester according to the method of Example 2 of CN103922948A) and 31.74 g (0.092 mol, 20%) sodium nitrite aqueous solution for 1 hour. After completion, react at 5° C. for 0.5 hour to obtain a diazo solution.

[0066] (2) In another 2000mL four-necked bottle, add 1.224g (0.012mol, 97%) cuprous chloride and 80g (0.8mol, 36.5%) hydrochloric acid. Control the reaction temperature to 10°C, and evenly add the diazo solution obtained in step (1) to the mixture over 1 hour. Then react at 10°C for 2 hours, take a sample and perform liquid chromatography control. If the diazonium salt is less than 0.5%, stop the reaction.

[0067] (3) The reaction solution was kept at 0°C for 0.7 hours and then filtered. The solid was washed twice with ice water to obtain 15.92 g of light yellow 2-chloro-3-nitrobenzoic acid solid. Quantitative analysis by liquid chromatography showed a purity of 95.51% and a yield of 94.3%.

[0068] Example 1

[0069] This embodiment provides a method for preparing 2-fluoro-3-nitro-N-(4-(perfluoropropane-2-yl)-2-(trifluoromethyl)phenyl)benzamide (referred to as nitroamide), the preparation method comprising the following steps:

[0070] (1) 83.0 g (0.4 mol, content 97%) of 2-chloro-3-nitrobenzoic acid, 83.0 g of toluene, and 66.8 g (0.56 mol, content 99%) of thionyl chloride were added, and the temperature was raised to reflux for reaction for 4 hours. After the reaction was completed, the solvent was removed under reduced pressure to obtain 95.3 g of 2-chloro-3-nitrobenzoyl chloride, which was directly used in the next step reaction.

[0071] (2) KF (81.2 g, 1.4 mol, content 99%), tetramethylammonium chloride (1.26 g, content 99%) and 18-crown-6 (1.26 g, content 99%) were added to a 1000 mL three-necked round-bottom flask in sequence. 95.3 g of the acid chloride prepared in step 1 was added to 42 g of acetonitrile to dissolve, and then poured into the above KF / catalyst system. The mixture was stirred and heated to 82° C. for reflux reaction. The reaction was continued for 20 h, cooled to room temperature, filtered, and the filter cake was washed twice with 80 g of acetonitrile. The filtrate was decompressed at 5 KPa to recover the acetonitrile. The residue was further decompressed and distilled at 250 Pa. The 90° C.-100° C. fraction was collected to obtain 67.6 g of 2-fluoro-3-nitrobenzoyl fluoride, with a content of 98.95% and a yield of 89% (total yield of two steps).

[0072] Mass spectrometry GC / MS: m / z=187;

[0073] 1 The H NMR (400 MHz, CDCl 3 ) data are as follows (δ [ppm]): 8.41-8.37 (m, 1H), 8.32-8.28 (m, 1H), 8.57-8.52 (m, 1H).

[0074] (3) In a 250 mL reaction kettle, 39.7 g (0.21 mol) of 2-fluoro-3-nitrobenzoyl fluoride, 67.1 g (0.2 mol) of decafluoroaniline, 0.2 g of DMAP, and 134.2 g of toluene were added in sequence, and the mixture was heated to 110° C. for reaction for 6 h. After cooling slightly, 40 g of 10% sodium carbonate solution was slowly added, and the mixture was stirred at 80° C. for 30 min. After hot separation, the organic layer was cooled to room temperature, and then placed in an ice machine and stirred at 0° C. for 3 h. After filtration and drying, 96.0 g of nitroamide yellow solid was obtained, with a content of 98.41% and a yield of 95%.

[0075] Mass spectrum LC / MS [M+1]: m / z=497;

[0076] 1H NMR (400 MHz, DMSO-d6) data are as follows (δ [ppm]): 10.74 (s, 1H), 8.35 (t, J = 8.5 Hz, 1H), 8.20-8.03 (m, 3H), 7.96 (s, 1H), 7.62 (t, J = 8.0 Hz, 1H).

[0077] Example 2

[0078] This embodiment provides a method for preparing 2-fluoro-3-nitro-N-(4-(perfluoropropane-2-yl)-2-(trifluoromethyl)phenyl)benzamide (referred to as nitroamide), the preparation method comprising the following steps:

[0079] (1) 83.0 g (0.4 mol, content 97%) of 2-chloro-3-nitrobenzoic acid, 83.0 g of toluene, and 66.8 g (0.56 mol, content 99%) of thionyl chloride were added, and the temperature was raised to reflux for reaction for 4 hours. After the reaction was completed, the solvent was removed under reduced pressure to obtain 96.2 g of 2-chloro-3-nitrobenzoyl chloride, which was directly used in the next step reaction.

[0080] (2) KF (81.2 g, 1.4 mol, content 99%), tetramethylammonium chloride (1.26 g, content 99%), and 18-crown ether-6 (1.26 g, content 99%) were added to a 1000 mL three-necked round-bottom flask in sequence. 96.2 g of the acyl chloride prepared in step 1 was added to 42 g of toluene to dissolve, and then poured into the KF / catalyst system, stirred and heated to 110°C for reflux reaction, reacted for 8 h, cooled to room temperature, filtered, and the filter cake was washed twice with 80 g of toluene. The filtrate was decompressed at 3 KPa to recover toluene, and the residue was further decompressed and distilled at 250 Pa. The 90°C-100°C fraction was collected to obtain 66.8 g of product with a content of 98.61% and a yield of 88% (total yield of two steps).

[0081] (3) In a 500 mL reaction kettle, 45.5 g (0.24 mol) of 2-fluoro-3-nitrobenzoyl fluoride, 67.1 g (0.2 mol) of decafluoroaniline, 0.2 g of DMAP, and 201.3 g of xylene were added in sequence, and the mixture was heated to 140° C. for reaction for 4 h. After cooling slightly, 40 g of 10% sodium hydroxide solution was slowly added, and the mixture was stirred at 80° C. for 30 min. After hot liquid separation, the organic layer was cooled to room temperature, and then placed in an ice machine and stirred at 5° C. for 3 h. After filtration and drying, 96.6 g of nitroamide yellow solid was obtained, with a content of 98.58% and a yield of 96%.

[0082] Example 3

[0083] This embodiment provides a method for preparing 2-fluoro-3-nitro-N-(4-(perfluoropropane-2-yl)-2-(trifluoromethyl)phenyl)benzamide (referred to as nitroamide), the preparation method comprising the following steps:

[0084] (1) 83.0 g (0.4 mol, content 97%) of 2-chloro-3-nitrobenzoic acid, 160 g of toluene, 0.2 g of pyridine, and 0.2 g of DMF were added, the temperature was raised to 40-50° C., and a toluene solution of triphosgene (60 g, 0.20 mol, content 99%, toluene 100 g) was added dropwise for 5-6 h. After the addition, the mixture was kept at 50° C. for 2 hours. After the reaction was completed, the solvent was removed under reduced pressure to obtain 94.6 g of 2-chloro-3-nitrobenzoyl chloride, which was directly used in the next step.

[0085] (2) KF (81.2 g, 1.4 mol, content 99%), tetramethylammonium chloride (1.26 g, content 99%), and 18-crown ether-6 (1.26 g, content 99%) were added to a 1000 mL three-necked round-bottom flask in sequence. 94.6 g of the acyl chloride prepared in step 1 was added to 42 g of xylene to dissolve, and then poured into the KF / catalyst system, stirred and heated to 130°C for reaction, and the reaction was continued for 8 h, cooled to room temperature, filtered, and the filter cake was washed twice with 80 g of xylene. The filtrate was decompressed at 3 KPa to recover xylene, and the residue was further decompressed and distilled at 250 Pa. The 90°C-100°C fraction was collected to obtain 62.4 g of product with a content of 98.56% and a yield of 82% (total yield of two steps).

[0086] (3) In a 500 mL reaction kettle, 45.4 g (0.24 mol) of 2-fluoro-3-nitrobenzoyl fluoride, 67.1 g (0.2 mol) of decafluoroaniline, 0.2 g of DMAP, and 67.1 g of toluene were added in sequence, and the mixture was heated to 110° C. for reaction for 3 h. After cooling slightly, 40 g of 10% sodium hydroxide solution was slowly added, and the mixture was stirred at 80° C. for 30 min. After hot liquid separation, the organic layer was cooled to room temperature, and then placed in an ice machine and stirred at 5° C. for 3 h. After filtration and drying, 96.7 g of nitroamide yellow solid was obtained, with a content of 98.50% and a yield of 96%.

[0087] Example 4

[0088] (1) 83.0 g (0.4 mol, content 97%) of 2-chloro-3-nitrobenzoic acid was added with 83.0 g of tetrahydrofuran, 0.2 g of pyridine and 0.2 g of DMF. The mixture was heated to 40-50° C. and a tetrahydrofuran solution of triphosgene (42.0 g of triphosgene, 0.14 mol, content 99% and 66 g of tetrahydrofuran) was added dropwise for 5-6 h. After the addition, the mixture was kept at 50° C. for 2 hours. After the reaction was completed, the solvent was removed under reduced pressure to obtain 96.6 g (yield) of 2-chloro-3-nitrobenzoyl chloride, which was directly used in the next step.

[0089] (2) KF (81.2 g, 1.4 mol, content 99%), tetramethylammonium chloride (1.26 g, content 99%), and 18-crown ether-6 (1.26 g, content 99%) were added to a 1000 mL three-necked round-bottom flask in sequence. 96.6 g of the acyl chloride prepared in step 1 was added to 42 g of chlorobenzene to dissolve, and then poured into the KF / catalyst system, stirred and heated to 140°C for reaction, reacted for 3 h, cooled to room temperature, filtered, and the filter cake was washed twice with 80 g of chlorobenzene. The filtrate was decompressed at 3 KPa to recover chlorobenzene, and the residue was further decompressed and distilled at 250 Pa. The 90°C-100°C fraction was collected to obtain 61.0 g of product with a content of 98.60% and a yield of 80% (two-step yield).

[0090] (3) In a 500 mL reaction kettle, 45.5 g (0.24 mol) of 2-fluoro-3-nitrobenzoyl fluoride, 67.1 g (0.2 mol) of decafluoroaniline, 3.4 g of DMAP, and 201.3 g of dichloromethane were added in sequence, and the mixture was heated to 40° C. for reaction for 8 h. After the reaction was completed, 40 g of 10% sodium hydroxide solution was slowly added, and the mixture was stirred at 35° C. for 30 min. After hot separation, the organic layer was cooled to room temperature, and then placed in an ice machine and stirred at 5° C. for 3 h. After filtration and drying, 94.7 g of nitroamide yellow solid was obtained, with a content of 98.78% and a yield of 94%.

[0091] Example 5

[0092] (1) 83.0 g (0.4 mol, content 97%) of 2-chloro-3-nitrobenzoic acid, 83.0 g of dichloromethane and 61.5 g (0.48 mol, content 99%) of oxalyl chloride were added, the temperature was raised to 40°C and refluxed for 2 h. After the reaction was completed, the solvent was removed under reduced pressure to obtain 95.8 g of 2-chloro-3-nitrobenzoyl chloride, which was directly used in the next step.

[0093] (2) KF (70.4 g, 1.2 mol, content 99%) was added to a 1000 mL three-necked round-bottom flask, 95.8 g of the acid chloride prepared in step 1 was added to 240 g of sulfolane to dissolve, and then poured into KF, stirred and heated to 120° C. for reaction for 2 h, cooled to room temperature, filtered, and the filter cake was washed twice with 80 g of sulfolane. The filtrate was distilled under reduced pressure at 300 Pa to collect 377.4 g of a mixture of product and sulfolane. The content of 2-fluoro-3-nitrobenzoyl fluoride was 16.66%, and the yield was 84% ​​(total yield of two steps).

[0094] (3) In a 500 mL reaction kettle, 269.5 g (0.24 mol) of 2-fluoro-3-nitrobenzoyl fluoride sulfolane solution, 67.1 g (0.2 mol) of decafluoroaniline and 0.2 g of DMAP were added in sequence, and the mixture was heated to 180° C. for reaction for 3 h. After the reaction, the solvent was removed, 67.1 g of toluene was added, and the mixture was heated to about 100° C. Then, 40 g of 10% sodium hydroxide solution was slowly added, and the mixture was stirred at 80° C. for 30 min. After hot separation, the organic layer was cooled to room temperature, and then placed in an ice machine and stirred at 5° C. for 3 h. After filtration and drying, 96.2 g of nitroamide yellow solid was obtained, with a content of 98.18% and a yield of 95%.

[0095] Example 6

[0096] (1) 83.0 g (0.4 mol, content 97%) of 2-chloro-3-nitrobenzoic acid, 83.0 g of toluene, and 118.4 g (1.0 mol, content 99%) of thionyl chloride were added, and the temperature was raised to reflux for reaction for 1 hour. After the reaction was completed, the solvent was removed under reduced pressure to obtain 96.9 g of 2-chloro-3-nitrobenzoyl chloride, which was directly used in the next step reaction.

[0097] (2) KF (81.2 g, 1.4 mol, content 99%) and 18-crown ether-6 (2.52 g, content 99%) were added to a 1000 mL three-necked round-bottom flask in sequence. 96.9 g of the acyl chloride prepared in step 1 was added to 42 g of toluene to dissolve, and then poured into the KF / catalyst system, stirred and heated to 110°C for reflux reaction, reacted for 60 h, cooled to room temperature, filtered, and the filter cake was washed twice with 80 g of toluene. The filtrate was decompressed at 3 KPa to recover toluene, and the residue was further decompressed and distilled at 250 Pa to collect the 90°C-100°C fraction to obtain 60.2 g of product with a content of 98.15% and a yield of 79% (total yield of two steps).

[0098] (3) In a 500 mL reaction kettle, 57.2 g (0.30 mol) of 2-fluoro-3-nitrobenzoyl fluoride, 67.1 g (0.2 mol) of decafluoroaniline, 0.2 g of DMAP, and 67.1 g of toluene were added in sequence, and the mixture was heated to 110° C. for reaction for 3 h. After cooling slightly, 100 g of 10% sodium hydroxide solution was slowly added, and the mixture was stirred at 80° C. for 30 min. After hot liquid separation, the organic layer was cooled to room temperature, and then placed in an ice machine and stirred at 5° C. for 3 h. After filtration and drying, 96.7 g of nitroamide yellow solid was obtained, with a content of 98.65% and a yield of 96%.

[0099] Example 7

[0100] (1) 83.0 g (0.4 mol, content 97%) of 2-chloro-3-nitrobenzoic acid were added with 83.0 g of chloroform and 66.8 g (0.56 mol, content 99%) of thionyl chloride, and the temperature was raised to reflux for reaction for 4 hours. After the reaction was completed, the solvent was removed under reduced pressure to obtain 95.9 g of 2-chloro-3-nitrobenzoyl chloride, which was directly used in the next step reaction.

[0101] (2) KF (81.2 g, 1.4 mol, content 99%), tetrabutylammonium bromide (1.26 g, content 99%), and 18-crown ether-6 (1.26 g, content 99%) were added to a 1000 mL three-necked round-bottom flask in sequence. 95.9 g of the acyl chloride prepared in step 1 was added to 42 g of toluene to dissolve, and then poured into the KF / catalyst system, stirred and heated to 110°C for reflux reaction, reacted for 32 h, cooled to room temperature, filtered, and the filter cake was washed twice with 80 g of toluene. The filtrate was decompressed at 3 KPa to recover toluene, and the residue was further decompressed and distilled at 250 Pa. The 90°C-100°C fraction was collected to obtain 58.0 g of product with a content of 98.91% and a yield of 77% (total yield of two steps).

[0102] (3) In a 500 mL reaction kettle, 45.4 g (0.24 mol) of 2-fluoro-3-nitrobenzoyl fluoride, 67.1 g (0.2 mol) of decafluoroaniline, 0.07 g of DMAP, and 201.3 g of chlorobenzene were added in sequence, and the mixture was heated to 140° C. for reaction for 7 h. After cooling slightly, 40 g of 10% sodium hydroxide solution was slowly added, and the mixture was stirred at 80° C. for 30 min. After hot liquid separation, the organic layer was cooled to room temperature, and then placed in an ice machine and stirred at 5° C. for 3 h. After filtration and drying, 95.8 g of nitroamide yellow solid was obtained, with a content of 98.82% and a yield of 95%.

[0103] Example 8

[0104] (1) 83.0 g (0.4 mol, content 97%) of 2-chloro-3-nitrobenzoic acid, 83.0 g of xylene, and 66.8 g (0.56 mol, content 99%) of thionyl chloride were added, and the temperature was raised to reflux for reaction for 4 hours. After the reaction was completed, the solvent was removed under reduced pressure to obtain 97.8 g of 2-chloro-3-nitrobenzoyl chloride, which was directly used in the next step reaction.

[0105] (2) KF (81.2 g, 1.4 mol, content 99%), hexadecyltrimethylammonium chloride (1.26 g, content 99%), and 18-crown ether-6 (1.26 g, content 99%) were added to a 1000 mL three-necked round-bottom flask in sequence. 97.8 g of the acyl chloride prepared in step 1 was added to 42 g of toluene to dissolve, and then poured into the KF / catalyst system, stirred and heated to 110°C for reflux reaction, reacted for 32 h, cooled to room temperature, filtered, and the filter cake was washed twice with 80 g of toluene. The filtrate was decompressed at 3 KPa to recover toluene, and the residue was further decompressed and distilled at 250 Pa. The 90°C-100°C fraction was collected to obtain 59.6 g of product with a content of 98.28% and a yield of 78% (total yield of two steps).

[0106] (3) In a 500 mL reaction kettle, 45.7 g (0.24 mol) of 2-fluoro-3-nitrobenzoyl fluoride, 67.1 g (0.2 mol) of decafluoroaniline, 1.7 g of DMAP, and 67.1 g of toluene were added in sequence, and the mixture was heated to 110° C. for reaction for 4 h. After cooling slightly, 40 g of 10% sodium hydroxide solution was slowly added, and the mixture was stirred at 80° C. for 30 min. After hot liquid separation, the organic layer was cooled to room temperature, and then placed in an ice machine and stirred at 5° C. for 3 h. After filtration and drying, 96.8 g of nitroamide yellow solid was obtained, with a content of 98.12% and a yield of 96%.

[0107] Example 9

[0108] (1) 83.0 g (0.4 mol, content 97%) of 2-chloro-3-nitrobenzoic acid, 83.0 g of chlorobenzene, and 66.8 g (0.56 mol, content 99%) of thionyl chloride were added, and the temperature was raised to reflux for reaction for 4 hours. After the reaction was completed, the solvent was removed under reduced pressure to obtain 97.8 g of 2-chloro-3-nitrobenzoyl chloride, which was directly used in the next step reaction.

[0109] (2) KF (81.2 g, 1.4 mol, content 99%), tetraphenylphosphine bromide (1.26 g, content 99%), and 18-crown ether-6 (1.26 g, content 99%) were added to a 1000 mL three-necked round-bottom flask in sequence. 97.8 g of the acyl chloride prepared in step 1 was added to 42 g of toluene to dissolve, and then poured into the KF / catalyst system, stirred and heated to 110°C for reflux reaction, reacted for 48 h, cooled to room temperature, filtered, and the filter cake was washed twice with 40 g of toluene. The filtrate was decompressed at 3 KPa to recover toluene, and the residue was further decompressed and distilled at 250 Pa. The 90°C-100°C fraction was collected to obtain 55.8 g of product with a content of 96.26% and a yield of 72% (two-step yield).

[0110] (3) In a 500 mL reaction kettle, 46.7 g (0.24 mol) of 2-fluoro-3-nitrobenzoyl fluoride, 67.1 g (0.2 mol) of decafluoroaniline, 0.2 g of DMAP, and 134.2 g of 1,2-dichloroethane were added in sequence, and the mixture was heated to 84°C for reaction for 8 h. After cooling slightly, 40 g of 10% sodium hydroxide solution was slowly added, and the mixture was stirred at 80°C for 30 min. After hot separation, the organic layer was cooled to room temperature, and then placed in an ice machine and stirred at 5°C for 3 h. After filtration and drying, 95.2 g of nitroamide yellow solid was obtained, with a content of 98.32% and a yield of 94%.

[0111] Example 10

[0112] (1) 83.0 g (0.4 mol, content 97%) of 2-chloro-3-nitrobenzoic acid, 83.0 g of benzene and 66.8 g (0.56 mol, content 99%) of thionyl chloride were added, and the temperature was raised to reflux for reaction for 6 hours. After the reaction was completed, the solvent was removed under reduced pressure to obtain 96.4 g of 2-chloro-3-nitrobenzoyl chloride, which was directly used in the next step reaction.

[0113] (2) KF (81.2 g, 1.4 mol, content 99%), nonylphenol polyoxyethylene ether (2.4 g, content 99%), and tetramethylammonium chloride (2.8 g, content 99%) were added to a 1000 mL three-necked round-bottom flask in sequence. 96.4 g of the acid chloride prepared in step 1 was added to 42 g of xylene to dissolve, then poured into the KF / catalyst system, 100 μL of water was added, the mixture was stirred and heated to 140°C for reflux reaction, the reaction was continued for 16 h, the mixture was cooled to room temperature, filtered, the filter cake was washed twice with 80 g of xylene, the filtrate was decompressed at 3 KPa to recover xylene, the residue was further decompressed and distilled at 250 Pa, and the 90°C-100°C fraction was collected to obtain 53.4 g of product with a content of 98.46% and a yield of 70% (two-step yield).

[0114] (3) In a 500 mL reaction kettle, 45.6 g (0.24 mol) of 2-fluoro-3-nitrobenzoyl fluoride, 67.1 g (0.2 mol) of decafluoroaniline, 0.2 g of DMAP, and 67.1 g of dichlorobenzene were added in sequence, and the mixture was heated to 180° C. for reaction for 3 h. After cooling slightly, 40 g of 10% sodium hydroxide solution was slowly added, and the mixture was stirred at 80° C. for 30 min. After hot liquid separation, the organic layer was cooled to room temperature, and then placed in an ice machine and stirred at 5° C. for 3 h. After filtration and drying, 96.1 g of nitroamide yellow solid was obtained, with a content of 98.72% and a yield of 96%.

[0115] The applicant declares that the present invention uses the above embodiments to illustrate the detailed method of the present invention, but the present invention is not limited to the above embodiments, that is, it does not mean that the present invention must rely on the above 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 preparing 2-fluoro-3-nitro-N-(4-(perfluoropropane-2-yl)-2-(trifluoromethyl)phenyl)benzamide, characterized in that: The preparation method comprises the following steps: (1) reacting 2-chloro-3-nitrobenzoic acid with a chlorinating agent to obtain 2-chloro-3-nitrobenzoyl chloride; (2) reacting the 2-chloro-3-nitrobenzoyl chloride obtained in step (1) with a fluorinating agent to obtain 2-fluoro-3-nitrobenzoyl fluoride; (3) condensing the 2-fluoro-3-nitrobenzoyl fluoride obtained in step (2) with 4-(perfluoropropane-2-yl)-2-(trifluoromethyl)aniline to obtain the 2-fluoro-3-nitro-N-(4-(perfluoropropane-2-yl)-2-(trifluoromethyl)phenyl)benzamide.

2. The preparation method according to claim 1, characterized in that: The chlorination reagent in step (1) is one or a combination of at least two of thionyl chloride, triphosgene, oxalyl chloride, phosphorus trichloride or phosphorus pentachloride.

3. The preparation method according to claim 2, characterized in that: The chlorination reagent is thionyl chloride or triphosgene.

4. The preparation method according to claim 1, characterized in that: The molar ratio of the 2-chloro-3-nitrobenzoic acid to the chlorination reagent in step (1) is 1:(0.35-2.5).

5. The preparation method according to claim 4, characterized in that: The molar ratio of the 2-chloro-3-nitrobenzoic acid to the chlorination reagent is 1:(0.5-2.0).

6. The preparation method according to claim 1, characterized in that: The reaction in step (1) is carried out in the presence of a solvent, and the solvent is any one of tetrahydrofuran, dichloromethane, 1,2-dichloroethane, chloroform, benzene, toluene, xylene, chlorobenzene or dichlorobenzene, or a combination of at least two thereof.

7. The preparation method according to claim 6, characterized in that: The solvent is toluene and / or xylene.

8. The preparation method according to claim 1, characterized in that: The reaction temperature in step (1) is 40-180°C.

9. The preparation method according to claim 8, characterized in that: The reaction temperature is 110-140°C.

10. The preparation method according to claim 1, characterized in that: The reaction time of step (1) is 1 to 8 hours.

11. The preparation method according to claim 10, characterized in that: The reaction time is 2 to 6 hours.

12. The preparation method according to claim 1, characterized in that: The fluorination agent in step (2) is potassium fluoride and / or cesium fluoride.

13. The preparation method according to claim 12, characterized in that: The fluoridation agent is potassium fluoride.

14. The preparation method according to claim 1, characterized in that: The molar ratio of 2-chloro-3-nitrobenzoyl chloride to the fluorination agent in step (2) is 1:(2.0-5.0).

15. The preparation method according to claim 1, characterized in that: The reaction in step (2) is carried out in the presence of a phase transfer catalyst, wherein the phase transfer catalyst is at least one of 18-crown ether-6, tetramethylammonium chloride, tetramethylammonium bromide, tetrabutylammonium bromide, hexadecyltrimethylammonium chloride, nonylphenol polyoxyethylene ether or tetraphenylphosphonium bromide.

16. The preparation method according to claim 15, characterized in that: The phase transfer catalyst is 18-crown ether-6 and / or tetramethylammonium chloride.

17. The preparation method according to claim 15, characterized in that: The mass ratio of the 2-chloro-3-nitrobenzoyl chloride to the phase transfer catalyst in step (2) is 1:(0% to 5.0%).

18. The preparation method according to claim 17, characterized in that: The mass ratio of the 2-chloro-3-nitrobenzoyl chloride to the phase transfer catalyst is 1:(1.0%-1.5%).

19. The preparation method according to claim 1, characterized in that: The reaction in step (2) is carried out in the presence of a solvent, wherein the solvent is any one of benzene, toluene, xylene, chlorobenzene, nitrobenzene, tetrahydrofuran, 2-methyltetrahydrofuran, acetonitrile, propionitrile, butyronitrile, N,N-dimethylformamide, N,N-dimethylacetamide, N-methylpyrrolidone, dimethyl sulfoxide or cyclopentane sulfone, or a combination of at least two thereof.

20. The preparation method according to claim 19, characterized in that: The solvent is toluene and / or xylene.

21. The preparation method according to claim 19, characterized in that: The mass ratio of the 2-chloro-3-nitrobenzoic acid to the solvent in step (2) is 1:(0.5-4.0).

22. The preparation method according to claim 1, characterized in that: The reaction temperature in step (2) is 60-180°C.

23. The preparation method according to claim 22, characterized in that: The reaction temperature is 80-120°C.

24. The preparation method according to claim 1, characterized in that: The reaction time of step (2) is 0.5 to 80 hours.

25. The preparation method according to claim 1, characterized in that: After the reaction in step (2) is completed, the reaction solution is filtered, and the filtrate is desolventized and then distilled under reduced pressure to obtain the 2-fluoro-3-nitrobenzoyl fluoride.

26. The preparation method according to claim 25, characterized in that: The filtrate desolventizing is to remove the solvent by vacuum distillation of the filtrate at a pressure of 2KPa-5KPa.

27. The preparation method according to claim 25, characterized in that: The pressure of the reduced pressure distillation after desolventization is 20Pa-500Pa.

28. The preparation method according to claim 1, characterized in that: The molar ratio of 2-fluoro-3-nitrobenzoyl fluoride to 4-(perfluoropropane-2-yl)-2-(trifluoromethyl)aniline in step (3) is (1-1.5):

1.

29. The preparation method according to claim 28, characterized in that: The molar ratio of the 2-fluoro-3-nitrobenzoyl fluoride to 4-(perfluoropropane-2-yl)-2-(trifluoromethyl)aniline is (1.1-1.3):

1.

30. The preparation method according to claim 1, characterized in that: The reaction in step (3) is carried out in the presence of a solvent, and the solvent is any one of dichloromethane, 1,2-dichloroethane, chloroform, benzene, toluene, xylene, chlorobenzene or dichlorobenzene, or a combination of at least two thereof.

31. The preparation method according to claim 30, characterized in that: The solvent is toluene and / or xylene.

32. The preparation method according to claim 30, characterized in that: The mass ratio of the 4-(perfluoropropane-2-yl)-2-(trifluoromethyl)aniline to the solvent in step (3) is 1:(1-5).

33. The preparation method according to claim 32, characterized in that: The mass ratio of the 4-(perfluoropropane-2-yl)-2-(trifluoromethyl)aniline to the solvent is 1:(2-4).

34. The preparation method according to claim 1, characterized in that: The reaction in step (3) is carried out in the presence of a catalyst, and the catalyst is 4-dimethylaminopyridine.

35. The preparation method according to claim 34, characterized in that: The amount of the catalyst used is 0.1%-5% of the mass of 4-(perfluoropropane-2-yl)-2-(trifluoromethyl)aniline.

36. The preparation method according to claim 1, characterized in that: The temperature of the condensation reaction in step (3) is 40 to 180°C.

37. The preparation method according to claim 36, characterized in that: The temperature of the condensation reaction is 110-140°C.

38. The preparation method according to claim 1, characterized in that: The condensation reaction time in step (3) is 3 to 8 hours.

39. The preparation method according to claim 38, characterized in that: The condensation reaction time is 4 to 6 hours.

40. The preparation method according to claim 1, characterized in that: After the condensation reaction in step (3) is completed, post-treatment is performed. The method comprises the following steps: adding alkali solution to the reaction system, stirring at 35-80°C for 10-40 minutes, separating the liquids while hot, cooling the obtained organic layer to room temperature, then stirring at 0-5°C for 1-3 hours, filtering and drying to obtain 2-fluoro-3-nitro-N-(4-(perfluoropropane-2-yl)-2-(trifluoromethyl)phenyl)benzamide.

41. The preparation method according to claim 40, characterized in that The alkali solution is an aqueous solution of one or a combination of at least two of hydroxides, carbonates or bicarbonates of alkali metals or alkaline earth metals.

42. The preparation method according to claim 41, characterized in that The alkali solution is sodium hydroxide solution or sodium carbonate solution.

43. The preparation method according to claim 1, characterized in that: The preparation method comprises the following steps: (1) reacting 2-chloro-3-nitrobenzoic acid with a chlorinating agent at a molar ratio of 1:(0.35-2.5) at 40-180° C. for 1-8 hours to obtain 2-chloro-3-nitrobenzoyl chloride; (2) The 2-chloro-3-nitrobenzoyl chloride obtained in step (1) and a fluorinating agent are reacted at a molar ratio of 1:(2.0-5.0) at 60-180° C. for 0.5-80 h. After the reaction is completed, the reaction solution is filtered, and the filtrate is desolventized and distilled under reduced pressure to obtain 2-fluoro-3-nitrobenzoyl fluoride; (3) condensing the 2-fluoro-3-nitrobenzoyl fluoride obtained in step (2) with 4-(perfluoropropane-2-yl)-2-(trifluoromethyl)aniline at a molar ratio of (1 to 1.5):1 and a temperature of 40 to 180° C. for 3 to 8 hours to obtain the 2-fluoro-3-nitro-N-(4-(perfluoropropane-2-yl)-2-(trifluoromethyl)phenyl)benzamide.

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