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CN113698315A - Synthetic method of 2-trifluoromethyl benzamide - Google Patents

Synthetic method of 2-trifluoromethyl benzamide Download PDF

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CN113698315A
CN113698315A CN202111030970.2A CN202111030970A CN113698315A CN 113698315 A CN113698315 A CN 113698315A CN 202111030970 A CN202111030970 A CN 202111030970A CN 113698315 A CN113698315 A CN 113698315A
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chloro
trifluoromethyl
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陈正伟
征玉荣
何彬
张莉笋
刘亮
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Inner Mongolia Lanke Biotechnology Co ltd
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Inner Mongolia Lanke Biotechnology Co ltd
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C231/00—Preparation of carboxylic acid amides
    • C07C231/06—Preparation of carboxylic acid amides from nitriles by transformation of cyano groups into carboxamide groups
    • C07C231/065—By hydration using metals or metallic ions as catalyst
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C17/00—Preparation of halogenated hydrocarbons
    • C07C17/093—Preparation of halogenated hydrocarbons by replacement by halogens
    • C07C17/20—Preparation of halogenated hydrocarbons by replacement by halogens of halogen atoms by other halogen atoms
    • C07C17/202—Preparation of halogenated hydrocarbons by replacement by halogens of halogen atoms by other halogen atoms two or more compounds being involved in the reaction
    • C07C17/208—Preparation of halogenated hydrocarbons by replacement by halogens of halogen atoms by other halogen atoms two or more compounds being involved in the reaction the other compound being MX
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C231/00—Preparation of carboxylic acid amides
    • C07C231/12—Preparation of carboxylic acid amides by reactions not involving the formation of carboxamide groups
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C253/00—Preparation of carboxylic acid nitriles
    • C07C253/14—Preparation of carboxylic acid nitriles by reaction of cyanides with halogen-containing compounds with replacement of halogen atoms by cyano groups
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C253/00—Preparation of carboxylic acid nitriles
    • C07C253/30—Preparation of carboxylic acid nitriles by reactions not involving the formation of cyano groups

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Abstract

The invention discloses a synthetic method of 2-trifluoromethyl benzamide, which comprises the following steps: 2, 3-dichlorotrifluorotoluene is used as a raw material, 2-fluoro-6-cyano trifluorotoluene is prepared through fluorination and cyano substitution, and then the 2-fluoro-6-cyano trifluorotoluene is subjected to hydrogenation dechlorination and then hydrolysis or the hydrolysis and then hydrogenation dechlorination to prepare the 2-trifluoromethyl benzamide. The 2-trifluoromethyl benzamide is synthesized by simple reaction, and the method has the characteristics that the raw materials are cheap and easy to obtain, and the isomer of the intermediate 2-fluoro-3-chloro-benzotrifluoride does not participate in the subsequent reaction and is easy to remove. Common flammable and explosive, highly toxic or difficultly-stored reagents in the existing synthetic method are not used in each reaction step, so that the harm to the environment and operators is avoided; meanwhile, the total yield of the product reaches more than 67 percent, and the purity is more than 97 percent.

Description

Synthetic method of 2-trifluoromethyl benzamide
Technical Field
The invention relates to the technical field of organic chemical synthesis, in particular to a synthetic method of 2-trifluoromethyl benzamide.
Background
The organic compound with the trifluoromethyl benzamide structure unit has good biological activity and is widely applied to the fields of medicines, pesticides, synthetic dyes and the like, so the organic compound has wide application prospect.
The synthesis of the disclosed 2-trifluoromethyl benzamide mainly comprises the following methods:
the first method, patent publication No. US2008/86008, discloses the preparation of 2-trifluoromethyl benzamide by using o-trifluoromethyl benzoyl chloride as a raw material and reacting with ammonia water.
The second method comprises the following steps: bulletin des societs Chimiques Belges,1930, vol.39, p.298,306,307 report the preparation of 2-trifluoromethylbenzoic acid by alkaline hydrolysis of 2-trifluoromethylbenzonitrile, the preparation of 2-trifluoromethylbenzoic acid ester by esterification, and the preparation of 2-trifluoromethylbenzamide by aminolysis.
The third method comprises the following steps: zhurnal Obshcheni Khimii,1953, vol.23, p.988, 990; engl. ausg. s.1033 reports preparation of 2-trifluoromethylbenzamide by chlorination, fluorine substitution of o-methylbenzonitrile as a raw material, followed by hydrolysis.
The method four comprises the following steps: journal of Organic Chemistry,2013, vol.78, #22, p.11126-11146 reports the preparation of 2-trifluoromethylbenzamide by reacting o-iodobenzamide with cuprous trifluoromethyl as the starting material.
Through comparison, the method I has less synthesis steps, but the preparation of the raw material o-trifluoromethyl benzoyl chloride necessarily uses a chlorination reagent, toxic hydrogen chloride and sulfur dioxide are released in the reaction process, the corrosion to equipment is large, and the method is not environment-friendly; the second method is longer, so that the total yield is lower; in the method III, o-methyl benzonitrile is taken as a raw material, and is subjected to chlorination and fluorine substitution, impurities with benzene ring chlorination or incomplete methyl chlorination may exist, and the operation is complex; in the fourth method, expensive and unstable trifluoromethyl cuprous is used as a raw material.
Therefore, the development of a process which has mild reaction conditions, simple operation, less three wastes, high yield and can be used for industrially producing the 2-trifluoromethyl benzamide is an urgent problem to be solved.
Disclosure of Invention
Therefore, the technical problem to be solved by the invention is to overcome the defects of low yield and large pollution of 2-trifluoromethyl benzamide in the prior art, so that the method for synthesizing the 2-trifluoromethyl benzamide is mild in condition, simple to operate, less in three wastes and high in yield.
Therefore, the invention provides a method for synthesizing 2-trifluoromethyl benzamide, which comprises the following steps:
(1) dissolving 2, 3-dichlorotrifluorotoluene and a fluorination reagent in a first solvent, adding a first catalyst, heating to 60-260 ℃ and reacting for 0.5-4 h to obtain 2-fluoro-3-chlorotrifluoromethane;
(2) adding a cyaniding reagent into a second solvent, adding 2-fluoro-3-chlorotrifluoromethane, and heating to react for 2-4 hours to obtain 2-chloro-6-trifluoromethylbenzonitrile;
(3) dissolving 2-chloro-6-trifluoromethyl benzonitrile in a third solvent, adding a second catalyst and a third catalyst, introducing hydrogen, and reacting for 1-16 h to obtain 2-trifluoromethyl benzonitrile;
(4) and adding the 2-trifluoromethyl benzonitrile into a fourth solvent, adding a fourth catalyst, and heating for reaction for 1-4 hours to obtain the 2-trifluoromethyl benzamide.
Preferably, the molar ratio of the 2-chloro-6-trifluoromethylbenzonitrile, the second catalyst and the third catalyst is 1: 0.9-3.5: 0.05 to 0.5; the molar ratio of the 2-trifluoromethyl benzonitrile to the fourth catalyst is 1: 0.1 to 5.0.
Preferably, the second catalyst is any one of triethylamine, diisopropylethylamine, trioctylamine, and Diazabicyclo (DBU); the third catalyst is any one of Ranney nickel, a 5% palladium-carbon catalyst, a 10% palladium hydroxide-carbon catalyst and a 5% platinum-carbon catalyst; the third solvent is any one or the combination of two or more of methanol, ethanol, isopropanol, 1, 4-dioxane, diethyl ether, tetrahydrofuran, methyl tert-butyl ether and water; the fourth catalyst is any one of sodium hydroxide, potassium hydroxide and lithium hydroxide; the fourth solvent is any one or the combination of two or more of water, methanol and ethanol.
Preferably, step (3) and step (4) are replaced simultaneously by:
dissolving 2-chloro-6-trifluoromethyl benzonitrile in a fifth solvent, adding a fifth catalyst, and heating for reaction for 1-4 h to obtain 2-chloro-6-trifluoromethyl benzamide;
adding 2-chloro-6-trifluoromethyl benzamide into a sixth solvent, adding a sixth catalyst and a seventh catalyst, introducing hydrogen, and reacting for 1-4 h to obtain 2-trifluoromethyl benzonitrile.
Preferably, the molar ratio of the 2-chloro-6-trifluoromethylbenzonitrile to the fifth catalyst is 1: 0.1 to 5.0; the molar ratio of the 2-chloro-6-trifluoromethyl benzamide to the sixth catalyst to the seventh catalyst is 1: 0.9-3.5: 0.05 to 0.5.
Preferably, the fifth catalyst is any one of sodium hydroxide, potassium hydroxide and lithium hydroxide; the fifth solvent is any one or a combination of two or more of water, methanol and ethanol; the sixth catalyst is any one of triethylamine, diisopropylethylamine, trioctylamine and Diazabicyclo (DBU); the seventh catalyst is any one of Ranney nickel, a 5% palladium-carbon catalyst, a 10% palladium hydroxide-carbon catalyst and a 5% platinum-carbon catalyst; the sixth solvent is any one or a combination of two or more of methanol, ethanol, isopropanol, 1, 4-dioxane, diethyl ether, tetrahydrofuran, methyl tert-butyl ether and water.
Preferably, the fluorinating agent is any one of sodium fluoride, potassium fluoride or calcium fluoride; the first catalyst is any one of triphenyl phosphorus bromide, triphenyl phosphorus chloride, triphenyl phosphorus, Diazabicyclo (DBU), triethylamine or diisopropylethylamine; the first solvent is any one of chlorobenzene, dichlorobenzene, N-dimethylformamide, N-dimethylacetamide, dimethyl sulfoxide, N-methylpyrrolidone, sulfolane or 1, 3-dimethylimidazolidinone.
Preferably, the molar ratio of the 2, 3-dichlorotrifluorotoluene, the fluorinating agent and the first catalyst is 1: 1.2-2.0: 0.01 to 1.5.
Preferably, the cyaniding reagent is any one of sodium cyanide, potassium cyanide or cuprous cyanide; the second solvent is any one of chlorobenzene, dichlorobenzene, N-dimethylformamide, N-dimethylacetamide, dimethyl sulfoxide, N-methylpyrrolidone, sulfolane or 1, 3-dimethylimidazolidinone;
preferably, the molar ratio of the 2-fluoro-3-chlorotrifluoromethylene to the cyanating agent is 1: 0.9 to 3.0.
The reaction process is as follows:
Figure BDA0003245241030000051
the technical scheme of the invention has the following advantages:
1. the synthesis method of 2-trifluoromethyl benzamide provided by the invention takes 2, 3-dichloro benzotrifluoride as a raw material, and synthesizes the 2-trifluoromethyl benzamide through simple reaction, and has the characteristics that the raw material is cheap and easy to obtain, the isomer of the intermediate (2-fluoro-3-chloro-benzotrifluoride) does not participate in the subsequent reaction, and is easy to remove, and the product is easy to purify;
2. according to the synthesis method of the 2-trifluoromethyl benzamide provided by the invention, common flammable and explosive, virulent or difficultly-preserved reagents in the existing synthesis method are not used in each reaction step, so that the harm to the environment and operators is avoided; meanwhile, the yield of the product reaches more than 67 percent, and the purity is more than 97 percent;
3. the synthetic method of 2-trifluoromethyl benzamide provided by the invention has the advantages of simple reaction operation, less three wastes, easy recovery of used reagents, good industrialization prospect and capability of providing a new idea suitable for industrial mass production of 2-trifluoromethyl benzamide.
Detailed Description
The following examples are provided to further understand the present invention, not to limit the scope of the present invention, but to provide the best mode, not to limit the content and the protection scope of the present invention, and any product similar or similar to the present invention, which is obtained by combining the present invention with other prior art features, falls within the protection scope of the present invention.
The examples do not show the specific experimental steps or conditions, and can be performed according to the conventional experimental steps described in the literature in the field. The reagents or instruments used are not indicated by manufacturers, and are all conventional reagent products which can be obtained commercially.
Example 1
1) Preparation of 2-fluoro-3-chlorotrifluoromethylene
215g of 2, 3-dichlorotrifluorotoluene, 73g of potassium fluoride, 7g of triphenylphosphine bromide and 430mL of 1, 3-dimethylimidazolidinone were put into a 1000mL three-necked flask equipped with a rectifying column, and the mixture was stirred, heated and refluxed. After reacting for 1h, 185g of colorless transparent liquid is slowly distilled out, and the GC analysis content is 93.9 percent, namely the 2-fluoro-3-chlorotrifluoromethane. The crude product yield was 93.2%. The crude product was used in the next reaction without purification.
2) Preparation of 2-chloro-6-trifluoromethylbenzonitrile
180g of 2-fluoro-3-chlorotrifluoromethane are dissolved in 360mL of dry N, N-dimethylacetamide, the temperature is raised to 90 ℃ and 42.0g of sodium cyanide are added slowly in portions. After the addition, stirring the mixture for 4 hours at the temperature of 90-100 ℃, and recovering the N, N-dimethylacetamide under reduced pressure. The residue was dissolved in 900mL of ethyl acetate, washed with water and a saturated aqueous solution of sodium chloride in this order, dried over anhydrous sodium sulfate, concentrated, and the residue was distilled under reduced pressure to give 163.6g of an off-white solid. Namely 2-chloro-6-trifluoromethyl benzonitrile. GC content 97.8% and yield 87.6%
3) Preparation of 2-trifluoromethylbenzonitrile
72g of 2-chloro-6-trifluoromethylbenzonitrile and 38.5g of triethylamine were dissolved in 200mL of tetrahydrofuran, and 7g of the solution was added5% Palladium on carbon catalyst, N2After the replacement, H is introduced2The reaction was stirred at 25 ℃ under 1.5atm for 16h, and the starting materials were analyzed by GC to be completely reacted. The reaction solution was filtered, and the filtrate was concentrated. And adding 250mL of water into the residue, fully stirring, then carrying out suction filtration, and fully washing the filter cake to obtain 55.0g of off-white solid, namely the 2-trifluoromethyl benzonitrile. HPLC content 98.2%, yield 92.0%.
4) Preparation of 2-trifluoromethylbenzamide
24g NaOH is dissolved in 200mL water, 34.2g 2-trifluoromethyl benzonitrile is added, the temperature is raised to 100 ℃, the reaction is stirred for 2h, and HPLC analysis shows that the raw materials are completely reacted. The reaction solution was cooled to room temperature, and a white solid was precipitated. Suction filtration and drying are carried out to obtain 34g of product with HPLC content of 98.8 percent and yield of 89.9 percent.
The total yield of the reaction was 67.5% and the HPLC purity of the product was 98.8%.
Example 2
1) Preparation of 2-fluoro-3-chlorotrifluoromethylene
215g of 2, 3-dichlorotrifluorotoluene, 73g of potassium fluoride, 7g of triphenylphosphine bromide and 430mL of 1, 3-dimethylimidazolidinone were put into a 1000mL three-necked flask equipped with a rectifying column, and the mixture was stirred, heated and refluxed. After reacting for 1h, 185g of colorless transparent liquid is slowly distilled out, and the GC analysis content is 93.9 percent, namely the 2-fluoro-3-chlorotrifluoromethane. The crude product yield was 93.2%. The crude product was used in the next reaction without purification.
2) Preparation of 2-chloro-6-trifluoromethylbenzonitrile
180g of 2-fluoro-3-chlorotrifluoromethane are dissolved in 360mL of dry N, N-dimethylacetamide, the temperature is raised to 90 ℃ and 42.0g of sodium cyanide are added slowly in portions. After the addition, stirring the mixture for 4 hours at the temperature of 90-100 ℃, and recovering the N, N-dimethylacetamide under reduced pressure. The residue was dissolved in 900mL of ethyl acetate, washed with water and a saturated aqueous solution of sodium chloride in this order, dried over anhydrous sodium sulfate, concentrated, and the residue was distilled under reduced pressure to give 163.6g of an off-white solid. Namely 2-chloro-6-trifluoromethyl benzonitrile. GC content 97.8% and yield 87.6%
3) Preparation of 2-chloro-6-trifluoromethylbenzamide
24g NaOH is dissolved in 200mL water, 41.1g 2-chloro-6-trifluoromethyl benzonitrile is added, the temperature is raised to 100 ℃, the reaction is stirred for 4h, and HPLC analysis shows that the raw materials are completely reacted. The reaction solution was cooled to room temperature, and a white solid was precipitated. Suction filtration and drying are carried out to obtain 39.6g of product with HPLC content of 96.8 percent and yield of 88.8 percent.
4) Preparation of 2-trifluoromethylbenzamide
22.4g 2-chloro-6-trifluoromethyl benzamide, 15.0g triethylamine were dissolved in 60mL tetrahydrofuran, 2g 5% palladium on carbon catalyst, N2After the replacement, H is introduced2The reaction was stirred at 25 ℃ under 1.5atm for 16h, and the starting materials were analyzed by GC to be completely reacted. The reaction solution was filtered, and the filtrate was concentrated. And adding 250mL of water into the residue, fully stirring, then carrying out suction filtration, and fully washing the filter cake to obtain 18.0g of off-white solid, namely the 2-trifluoromethyl benzamide. HPLC content 97.3%, yield 95.2%.
The total yield of the reaction is 69.0%, and the HPLC purity of the product is 97.3%.
Example 3
1) Preparation of 2-fluoro-3-chlorotrifluoromethylene
215g of 2, 3-dichlorotrifluorotoluene, 83g of sodium fluoride, 10g of diisopropylethylamine and 400mL of N-methylpyrrolidone were put into a 1000mL three-necked flask equipped with a rectifying column, and the reaction was refluxed while being stirred. After 4 hours of reaction, 183g of colorless transparent liquid was slowly distilled off, and the content by GC analysis was 93.5%, which was 2-fluoro-3-chlorotrifluoromethane. The crude product yield was 92.2%. The crude product was used in the next reaction without purification.
2) Preparation of 2-chloro-6-trifluoromethylbenzonitrile
180g of 2-fluoro-3-chlorotrifluoromethylene are dissolved in 360mL of dry dimethyl sulfoxide, the temperature is raised to 90 ℃ and 177.1g of potassium cyanide are slowly added in portions. After the completion of the addition, the reaction was refluxed for 2 hours, and the residue was dissolved in 900mL of ethyl acetate after distillation under reduced pressure, washed with water and a saturated aqueous solution of sodium chloride in this order, dried over anhydrous sodium sulfate, concentrated, and the residue was distilled under reduced pressure to give 162.9g of an off-white solid. Namely 2-chloro-6-trifluoromethyl benzonitrile. The GC content was 97.8% and the yield was 87.2%.
3) Preparation of 2-trifluoromethylbenzonitrile
72g of 2-chloro-6-trifluoromethylbenzonitrile and 55.5g of triethylamine were dissolved in 200mL of tetrahydrofuran, and the resulting solution was added15g of 5% platinum-carbon catalyst, N2After the replacement, H is introduced2The reaction was stirred at 25 ℃ under 1.5atm for 16h, and the starting materials were analyzed by GC to be completely reacted. The reaction solution was filtered, and the filtrate was concentrated. And adding 250mL of water into the residue, fully stirring, then carrying out suction filtration, and fully washing the filter cake to obtain 55.8g of off-white solid, namely the 2-trifluoromethyl benzonitrile. HPLC content 98.1% and yield 93.3%.
4) Preparation of 2-trifluoromethylbenzamide
12g NaOH is dissolved in 200mL water, 34.2g 2-trifluoromethyl benzonitrile is added, the temperature is raised to 100 ℃, the reaction is stirred for 2h, and HPLC analysis shows that the raw materials are completely reacted. The reaction solution was cooled to room temperature, and a white solid was precipitated. Suction filtration and drying are carried out to obtain 34g of product with HPLC content of 98.8 percent and yield of 89.9 percent.
The total yield of the reaction was 67.4% and the HPLC purity of the product was 98.8%.
Example 4
1) Preparation of 2-fluoro-3-chlorotrifluoromethylene
215g of 2, 3-dichlorotrifluorotoluene, 83g of sodium fluoride, 10g of diisopropylethylamine and 400mL of methyl pyrrolidone were put into a 1000mL three-necked flask equipped with a rectifying column, and the reaction was refluxed while being stirred. After 4 hours of reaction, 183g of colorless transparent liquid was slowly distilled off, and the content by GC analysis was 93.5%, which was 2-fluoro-3-chlorotrifluoromethane. The crude product yield was 92.2%. The crude product was used in the next reaction without purification.
2) Preparation of 2-chloro-6-trifluoromethylbenzonitrile
180g of 2-fluoro-3-chlorotrifluoromethylene are dissolved in 360mL of dry dimethyl sulfoxide, the temperature is raised to 90 ℃ and 177.1g of potassium cyanide are slowly added in portions. After the completion of the addition, the reaction was refluxed for 2 hours, and the residue was dissolved in 900mL of ethyl acetate after distillation under reduced pressure, washed with water and a saturated aqueous solution of sodium chloride in this order, dried over anhydrous sodium sulfate, concentrated, and the residue was distilled under reduced pressure to give 162.9g of an off-white solid. Namely 2-chloro-6-trifluoromethyl benzonitrile. The GC content was 97.8% and the yield was 87.2%.
3) Preparation of 2-chloro-6-trifluoromethylbenzamide
40g NaOH is dissolved in 200mL water, 41.1g 2-chloro-6-trifluoromethyl benzonitrile is added, the temperature is raised to 100 ℃, the reaction is stirred for 4h, and HPLC analysis shows that the raw materials are completely reacted. The reaction solution was cooled to room temperature, and a white solid was precipitated. Suction filtration and drying are carried out to obtain 39.7g of product, the HPLC content is 96.9 percent, and the yield is 89.0 percent.
4) Preparation of 2-trifluoromethylbenzamide
22.4g 2-chloro-6-trifluoromethyl benzonitrile and 35.3g trioctylamine were dissolved in 60mL tetrahydrofuran, and 2g 5% palladium on carbon catalyst, N2After the replacement, H is introduced2The reaction was stirred at 25 ℃ under 1.5atm for 16h, and the starting materials were analyzed by GC to be completely reacted. The reaction solution was filtered, and the filtrate was concentrated. And adding 250mL of water into the residue, fully stirring, then carrying out suction filtration, and fully washing the filter cake to obtain 17.8g of off-white solid, namely the 2-trifluoromethyl benzamide. HPLC content 97.3%, yield 94.1%.
The total yield of the reaction is 67.3%, and the HPLC purity of the product is 97.3%.
It should be understood that the above examples are only for clarity of illustration and are not intended to limit the embodiments. Other variations and modifications will be apparent to persons skilled in the art in light of the above description. And are neither required nor exhaustive of all embodiments. And obvious variations or modifications therefrom are within the scope of the invention.

Claims (10)

1. The synthesis method of 2-trifluoromethyl benzamide is characterized by comprising the following steps:
(1) dissolving 2, 3-dichlorotrifluorotoluene and a fluorination reagent in a first solvent, adding a first catalyst, heating to 60-260 ℃ and reacting for 0.5-4 h to obtain 2-fluoro-3-chlorotrifluoromethane;
(2) adding a cyaniding reagent into a second solvent, adding 2-fluoro-3-chlorotrifluoromethane, and heating to react for 2-4 hours to obtain 2-chloro-6-trifluoromethylbenzonitrile;
(3) dissolving 2-chloro-6-trifluoromethyl benzonitrile in a third solvent, adding a second catalyst and a third catalyst, introducing hydrogen, and reacting for 1-16 h to obtain 2-trifluoromethyl benzonitrile;
(4) and adding the 2-trifluoromethyl benzonitrile into a fourth solvent, adding a fourth catalyst, and heating for reaction for 1-4 hours to obtain the 2-trifluoromethyl benzamide.
2. The method for synthesizing 2-trifluoromethylbenzamide according to claim 1, wherein the molar ratio of the 2-chloro-6-trifluoromethylbenzonitrile, the second catalyst and the third catalyst is 1: 0.9-3.5: 0.05 to 0.5;
the molar ratio of the 2-trifluoromethyl benzonitrile to the fourth catalyst is 1: 0.1 to 5.0.
3. The method for synthesizing 2-trifluoromethyl benzamide according to claim 1 or 2, wherein the second catalyst is any one of triethylamine, diisopropylethylamine, trioctylamine, and diazabicyclo;
the third catalyst is any one of Ranney nickel, a 5% palladium-carbon catalyst, a 10% palladium hydroxide-carbon catalyst and a 5% platinum-carbon catalyst;
the third solvent is any one or the combination of two or more of methanol, ethanol, isopropanol, 1, 4-dioxane, diethyl ether, tetrahydrofuran, methyl tert-butyl ether and water;
the fourth catalyst is any one of sodium hydroxide, potassium hydroxide and lithium hydroxide;
the fourth solvent is any one or the combination of two or more of water, methanol and ethanol.
4. The method for synthesizing 2-trifluoromethylbenzamide according to claim 1, wherein the step (3) and the step (4) are simultaneously replaced by the following steps:
dissolving 2-chloro-6-trifluoromethyl benzonitrile in a fifth solvent, adding a fifth catalyst, and heating for reaction for 1-4 h to obtain 2-chloro-6-trifluoromethyl benzamide;
adding 2-chloro-6-trifluoromethyl benzamide into a sixth solvent, adding a sixth catalyst and a seventh catalyst, introducing hydrogen, and reacting for 1-4 h to obtain 2-trifluoromethyl benzonitrile.
5. The method for synthesizing 2-trifluoromethylbenzamide according to claim 4, wherein the molar ratio of the 2-chloro-6-trifluoromethylbenzonitrile to the fifth catalyst is 1: 0.1 to 5.0;
the molar ratio of the 2-chloro-6-trifluoromethyl benzamide to the sixth catalyst to the seventh catalyst is 1: 0.9-3.5: 0.05 to 0.5.
6. The method for synthesizing 2-trifluoromethylbenzamide according to claim 4 or 5, wherein the fifth catalyst is any one of sodium hydroxide, potassium hydroxide and lithium hydroxide;
the fifth solvent is any one or a combination of two or more of water, methanol and ethanol;
the sixth catalyst is any one of triethylamine, diisopropylethylamine, trioctylamine and diazabicyclo;
the seventh catalyst is any one of Ranney nickel, a 5% palladium-carbon catalyst, a 10% palladium hydroxide-carbon catalyst and a 5% platinum-carbon catalyst;
the sixth solvent is any one or a combination of two or more of methanol, ethanol, isopropanol, 1, 4-dioxane, diethyl ether, tetrahydrofuran, methyl tert-butyl ether and water.
7. The method for synthesizing 2-trifluoromethylbenzamide according to any of claims 1 to 6, wherein the fluorinating agent is any of sodium fluoride, potassium fluoride or calcium fluoride;
the first catalyst is any one of triphenyl phosphonium bromide, triphenyl phosphonium chloride, triphenyl phosphonium, diazabicyclo, triethylamine or diisopropylethylamine;
the first solvent is any one of chlorobenzene, dichlorobenzene, N-dimethylformamide, N-dimethylacetamide, dimethyl sulfoxide, N-methylpyrrolidone, sulfolane or 1, 3-dimethylimidazolidinone.
8. The method for synthesizing 2-trifluoromethylbenzamide according to claim 7, wherein the molar ratio of the 2, 3-dichlorotrifluorotoluene, the fluorinating agent and the first catalyst is 1: 1.2-2.0: 0.01 to 1.5.
9. The method for synthesizing 2-trifluoromethyl benzamide according to claim 7, wherein the cyanidation reagent is any one of sodium cyanide, potassium cyanide or cuprous cyanide;
the second solvent is any one of chlorobenzene, dichlorobenzene, N-dimethylformamide, N-dimethylacetamide, dimethyl sulfoxide, N-methylpyrrolidone, sulfolane or 1, 3-dimethylimidazolidinone.
10. The method for synthesizing 2-trifluoromethylbenzamide according to claim 7, wherein the molar ratio of the 2-fluoro-3-chlorotrifluoromethylene to the cyanating reagent is 1: 0.9 to 3.0.
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