CN113880725A - A kind of preparation method of o-trifluoromethylbenzamide - Google Patents

A kind of preparation method of o-trifluoromethylbenzamide Download PDF

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CN113880725A
CN113880725A CN202111232586.0A CN202111232586A CN113880725A CN 113880725 A CN113880725 A CN 113880725A CN 202111232586 A CN202111232586 A CN 202111232586A CN 113880725 A CN113880725 A CN 113880725A
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潘强彪
陈静华
谢四维
李俊奇
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Wei Zhejiang Huaxin Materials Ltd By Share 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
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
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    • C07C17/00—Preparation of halogenated hydrocarbons
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    • C—CHEMISTRY; METALLURGY
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    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
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Abstract

本发明公开了一种邻三氟甲基苯甲酰胺的制备方法。该制备方法包括如下步骤：(1)在有机溶剂中，将邻硝基三氟甲苯和氟化盐进行如下所示的脱硝氟代反应，得到邻氟三氟甲苯；(2)在有机溶剂中，将邻氟三氟甲苯和氰基化试剂进行如下所示的脱氟氰代反应，得到邻三氟甲基苯腈；(3)在碱存在下，将邻三氟甲基苯腈、过氧化氢进行如下所示的水解反应。该制备方法后处理简单，产物纯度高，杂质少，收率高。

Figure DDA0003316572660000011
The invention discloses a preparation method of o-trifluoromethylbenzamide. The preparation method includes the following steps: (1) in an organic solvent, performing the denitration and fluorination reaction with o-nitrotrifluorotoluene and a fluoride salt as shown below to obtain o-fluorotrifluorotoluene; (2) in an organic solvent , the o-fluorotrifluorotoluene and the cyanating reagent are subjected to the defluorocyanation reaction shown below to obtain o-trifluoromethyl benzonitrile; (3) in the presence of a base, the o-trifluoromethyl benzonitrile, the per Hydrogen oxide undergoes a hydrolysis reaction as shown below. The preparation method has simple post-processing, high product purity, few impurities and high yield.
Figure DDA0003316572660000011

Description

Preparation method of o-trifluoromethyl benzamide
Technical Field
The invention relates to a preparation method of o-trifluoromethyl benzamide.
Background
The o-trifluoromethyl benzamide is a white solid and is an important fluorine-containing fine chemical intermediate. The synthesis method of the o-trifluoromethyl benzamide has few domestic and foreign literature reports, the existing method for synthesizing the intermediate mainly uses o-trifluoromethyl benzoic acid as a raw material, the o-trifluoromethyl benzoyl chloride is obtained by acylation reaction of the o-trifluoromethyl benzoic acid and thionyl chloride, and then the o-trifluoromethyl benzamide is obtained by amidation reaction of the o-trifluoromethyl benzoic acid and ammonia.
Disclosure of Invention
In order to solve the problems, the invention provides a method for synthesizing o-trifluoromethyl benzamide. The method takes ortho-nitrobenzotrifluoride as a raw material, carries out denitration and fluorination with fluoride salt to generate ortho-fluorobenzotrifluoride, carries out dehydrofluorination with a cyanation reagent to generate ortho-trifluoromethylbenzonitrile, and finally carries out hydrolysis reaction with hydrogen peroxide to generate the ortho-trifluoromethylbenzamide, wherein the purity is over 99.6 percent, the impurity types are few, and the product quality is stable.
The invention provides a preparation method of o-fluoro benzotrifluoride, which comprises the following steps: in an organic solvent, carrying out denitration and fluorination reaction on ortho-nitrobenzotrifluoride and fluoride salt as shown in the specification to obtain ortho-fluorobenzotrifluoride;
Figure BDA0003316572650000011
the organic solvent may be an aprotic polar solvent. The aprotic polar solvent can be one or more of a ketone solvent, an ether solvent, an amide solvent and a sulfone solvent. The ketone solvent is preferably acetone. The ethereal solvent is preferably tetrahydrofuran. The amide solvent is preferably one or more of N, N-dimethylformamide, N-dimethylacetamide, N-methylpyrrolidone, and hexamethylphosphoramide, for example, N-dimethylformamide. The sulfone solvent is preferably dimethyl sulfoxide and/or sulfolane.
The fluoride salt may be one or more of sodium fluoride, potassium fluoride, cesium fluoride, tetramethylammonium fluoride and tetrabutylammonium fluoride, such as tetramethylammonium fluoride and/or potassium fluoride.
The organic solvent may be used in an amount conventional in the art for reactions of this type. The molar volume of the o-nitrobenzotrifluoride and the organic solvent can be 1-3 mol/L, such as 2-2.5 mol/L.
The molar ratio of the fluoride salt to the ortho-nitrobenzotrifluoride can be 1.0-2.5: 1, such as 1.3-2.0: 1.
The reaction temperature of the reaction can be 25-250 ℃, for example 110-210 ℃.
The progress of the reaction can be monitored by conventional test methods in the art (e.g., TLC, HPLC, GC, or NMR), and is generally determined as the end point of the reaction when ortho-nitrobenzotrifluoride is no longer reacted. The reaction time of the reaction can be 2.5 to 4 hours.
The reaction may also include the following post-treatment steps: filtration and separation of the product from the filtrate. The separation is preferably by distillation.
The invention also provides a preparation method of o-trifluoromethyl benzonitrile, which comprises the following steps:
(1) preparing o-fluorotrifluorotoluene according to the preparation method of o-fluorotrifluorotoluene;
(2) in an organic solvent, carrying out the defluorination cyanation reaction of the o-fluorobenzotrifluoride and a cyanation reagent as shown in the specification to obtain o-trifluoromethylbenzonitrile;
Figure BDA0003316572650000021
in the defluorination cyanation reaction, the organic solvent can be an aprotic polar solvent, and the aprotic polar solvent can be one or more of a ketone solvent, an ether solvent, an amide solvent and a sulfone solvent. The ketone solvent is preferably acetone. The ethereal solvent is preferably tetrahydrofuran. The amide solvent is preferably one or more of N, N-dimethylformamide, N-dimethylacetamide, N-methylpyrrolidone, and hexamethylphosphoramide, for example, N-dimethylformamide. The sulfone solvent is preferably dimethyl sulfoxide and/or sulfolane.
In the defluorination cyanation reaction, the cyanation reagent can be sodium cyanide or potassium cyanide.
The organic solvent may be used in an amount conventional in the art for reactions of this type. The molar volume of the o-fluorobenzotrifluoride and the organic solvent can be 1-3 mol/L, such as 2-2.5 mol/L.
In the dehydrofluorination reaction, the molar ratio of the cyanation reagent to the o-fluorobenzotrifluoride may be 1.0-2.0: 1, for example, 1.1-1.6: 1.
The reaction temperature of the dehydrofluorination reaction can be 50-200 ℃, for example 90-120 ℃, and also for example 100 ℃.
The progress of the reaction of the dehydrofluorination can be monitored by a conventional test method in the art (e.g., TLC, HPLC, GC or NMR), and the end point of the reaction is usually determined when ortho-nitrobenzotrifluoride is no longer reacted. The reaction time of the defluorination and cyanation reaction can be 5-6 hours.
The defluorination cyanation reaction can also comprise the following post-treatment steps: filtration and separation of the product from the filtrate. The separation mode is preferably vacuum distillation.
The invention provides a preparation method of o-trifluoromethyl benzamide, which comprises the following steps:
(1) the o-trifluoromethyl benzonitrile is prepared according to the preparation method of the o-trifluoromethyl benzonitrile;
(2) in a solvent, in the presence of alkali, carrying out hydrolysis reaction on ortho-trifluoromethyl benzonitrile and hydrogen peroxide as shown in the specification to obtain ortho-trifluoromethyl benzamide;
Figure BDA0003316572650000031
in the hydrolysis reaction, the mass concentration of the hydrogen peroxide can be 27-50%, for example 30%.
In the hydrolysis reaction, the molar ratio of the hydrogen peroxide to the o-trifluoromethylbenzonitrile can be 2.0-3.0: 1, for example, 2.5-2.8: 1.
In the hydrolysis reaction, the base may be one conventionally used in the art, and is preferably one of sodium carbonate, potassium carbonate, sodium hydroxide and potassium hydroxide, such as sodium hydroxide. In the hydrolysis reaction, the pH of the reaction solution of the reaction can be 10-13, for example 11-12.
In the hydrolysis reaction, the adding time of the hydrogen peroxide can be 4-8 hours, such as 4.5-5 hours. The hydrolysis reaction is a two-phase reaction, and the reaction requires a certain mass transfer time.
The reaction temperature of the hydrolysis reaction can be 30-90 ℃, for example, 40-50 ℃.
In the hydrolysis reaction, the solvent may be water. Part of the solvent may be used to form an alkaline solution with the base. The alkali solution preferably has a mass concentration of 5% to 30%, for example 20%.
The hydrolysis reaction can also comprise the following post-treatment steps: filtering and drying.
The invention also provides a preparation method of the o-trifluoromethyl benzamide, which comprises the following steps:
(1) in an organic solvent, carrying out the defluorination cyanation reaction of the o-fluorobenzotrifluoride and a cyanation reagent as shown in the specification to obtain o-trifluoromethylbenzonitrile;
Figure BDA0003316572650000041
(2) in the presence of alkali, o-trifluoromethylbenzonitrile and hydrogen peroxide are subjected to hydrolysis reaction as shown below;
Figure BDA0003316572650000042
in the above-mentioned dehydrofluorination reaction and the above-mentioned hydrolysis reaction, the respective reaction conditions may be as described above.
The invention also provides a preparation method of the o-trifluoromethyl benzonitrile, which comprises the following steps: in an organic solvent, carrying out the defluorination cyanation reaction of the o-fluorobenzotrifluoride and a cyanation reagent as shown in the specification to obtain o-trifluoromethylbenzonitrile;
Figure BDA0003316572650000043
in the preparation method of the o-trifluoromethylbenzonitrile, each reaction condition can be as described above.
On the basis of the common knowledge in the field, the above preferred conditions can be combined randomly to obtain the preferred embodiments of the invention.
The reagents and starting materials used in the present invention are commercially available.
The positive progress effects of the invention are as follows:
(1) the invention provides a preparation method of o-trifluoromethyl benzamide and an intermediate thereof, which takes a byproduct o-nitrobenzotrifluoride generated when an enterprise produces m-nitrobenzotrifluoride as a raw material, exploits the potential value of the byproduct and carries out resource utilization on the byproduct.
(2) The method has the advantages of less three wastes, simple post-treatment, resource utilization of nitrite and fluoride produced in the preparation process, no use of organic solvent when preparing the o-trifluoromethyl benzamide through hydrolysis reaction, oxygen as a byproduct, simple post-treatment and environmental protection.
(3) The prepared o-trifluoromethyl benzamide has high purity, less impurities and high yield.
Detailed Description
The invention is further illustrated by the following examples, which are not intended to limit the scope of the invention. The experimental methods without specifying specific conditions in the following examples were selected according to the conventional methods and conditions, or according to the commercial instructions.
In the following examples, DMF represents N, N-dimethylformamide.
Example 1
(1) Denitration fluorination
Adding o-nitrobenzotrifluoride (19.1g,0.10mol), anhydrous tetramethylammonium fluoride (12.1g,0.13mol) and 40mL of DMF (solvent) into a reaction flask, heating to 110 ℃, keeping the temperature for reaction for 2.5h, cooling to room temperature after the reaction is finished, filtering to remove generated potassium nitrite, evaporating 15.6g of colorless oily liquid o-fluorobenzotrifluoride from the filtrate, ensuring the purity to be 99.2 percent, obtaining the yield to be 95.1 percent, and then decompressing and recovering the DMF.
The product obtained was analyzed by GC comparison with a standard compound (purchased ortho-fluorobenzotrifluoride) and the retention time was consistent and was 2.233 min.
The GC analysis method was as follows:
item Parameter(s)
Chromatographic column OV-1701
Column length x column inner diameter x film thickness 30m×0.5mm×0.32μm
Vaporization chamber temperature/. degree.C 280
FID Detector temperature/. degree.C 280
Column box temperature/. degree.C 170
Sample size/. mu.L 0.1
Carrier gas N2
Flow of carrier gas/(mL/min) 0.6
Air flow/(mL/min) 300
Hydrogen flow/(mL/min) 30
Split ratio 50:1
(2) Defluorination of cyanogen
Adding ortho-fluoro benzotrifluoride (16.4g,0.10mol), potassium cyanide (7.2g,0.11mol) and 40mL of DMF (dimethyl formamide) solvent into a reaction flask, heating to 100 ℃, keeping the temperature for 5 hours for reaction, cooling to room temperature after the reaction is finished, filtering to remove the generated potassium fluoride and unreacted potassium cyanide, carrying out vacuum rectification on the filtrate, recovering DMF, and obtaining 16.1g of o-trifluoromethylbenzonitrile as colorless oily liquid, wherein the purity is 99.3%, and the yield is 94.1%.
The prepared product was analyzed by LC comparison with a standard compound (purchased o-trifluoromethylbenzonitrile) and the retention time of both was consistent and was 4.208 min.
The LC analysis method was as follows:
item Parameter(s)
Chromatographic column ZORBAX Eclopse XDB-C18(4.6mm*250mm*5μm)
Column temperature/. degree.C 35
Mobile phase Water methanol 30:70(v/v)
Flow rate/(mL/min) 1.0mL/min
Sample size/. mu.L 1
Detection wavelength/nm 254
Detection time/min 13
(3) Hydrolysis
Adding the prepared o-trifluoromethylbenzonitrile (84g,0.49mol) into a flask, slowly dropwise adding 139g of aqueous solution of hydrogen peroxide (30%, 139g,1.23mol) into the flask under stirring, adjusting the pH of a reaction system to 11-12 by using aqueous solution of sodium hydroxide (30%) during reaction, controlling the reaction temperature to 40-50 ℃, and after 5h of dropwise addition of the aqueous solution of hydrogen peroxide, generating a large amount of white needle-shaped crystals. Stopping reaction, filtering, and drying a filter cake to obtain 91g of white solid o-trifluoromethyl benzamide, wherein the purity is 99.6 percent, and the yield is 98 percent.
The product of the preparation was analyzed by LC comparison with a standard compound (purchased o-trifluoromethylbenzamide) and the retention time was consistent with 2.747 min.
The LC analysis method is the same as that in the step (2).
Example 2
(1) Denitration fluorination
Adding o-nitrobenzotrifluoride (19.1g,0.10mol), 11.6g anhydrous potassium fluoride (11.6g,0.20mol) and 50mL solvent sulfolane into a reaction flask, heating to 210 ℃, keeping the temperature for reaction for 4h, cooling to room temperature after the reaction is finished, filtering to remove generated potassium nitrite and unreacted potassium fluoride, evaporating 15.3g of colorless oily liquid o-fluorobenzotrifluoride from the filtrate, ensuring the purity to be 99.0 percent and the yield to be 93.3 percent, and then decompressing and recovering DMF.
The product obtained was analyzed by GC comparison with a standard compound (purchased ortho-fluorobenzotrifluoride) and the retention time was consistent and was 2.233 min.
The GC analysis method was the same as that in step (1) of example 1.
(2) Defluorination of cyanogen
Adding ortho-fluoro benzotrifluoride (16.4g,0.10mol), sodium cyanide (7.8g,0.16mol) and 50mL of DMF (dimethyl formamide) solvent into a reaction flask, heating to 120 ℃, keeping the temperature for reaction for 6h, cooling to room temperature after the reaction is finished, filtering to remove the generated sodium fluoride and unreacted sodium cyanide, carrying out reduced pressure rectification on the filtrate, recovering DMF, and obtaining 16.6g of o-trifluoromethylbenzonitrile as colorless oily liquid, wherein the purity is 99.1%, and the yield is 97.1%.
The prepared product was analyzed by LC comparison with a standard compound (purchased o-trifluoromethylbenzonitrile) and the retention time of both was consistent and was 4.208 min.
The LC analysis method was the same as that in step (2) of example 1.
(3) Hydrolysis
Adding the prepared o-trifluoromethylbenzonitrile (100.8g,0.53mol) into a flask, slowly dropwise adding an aqueous solution of hydrogen peroxide (50%, 100.8g,1.48mol) into the flask under stirring, adjusting the pH of a reaction system to 11-12 by using an aqueous solution of sodium hydroxide (20%) during reaction, controlling the reaction temperature to be 40-50 ℃, and after the dropwise addition of the aqueous solution of hydrogen peroxide is finished for 4.5h, generating a large amount of white needle-shaped crystals. Stopping reaction, filtering, and drying the filter cake to obtain 110.3g of white solid o-trifluoromethyl benzamide, wherein the purity is 99.9 percent and the yield is 99 percent.
The product of the preparation was analyzed by LC comparison with a standard compound (purchased o-trifluoromethylbenzamide) and the retention time was consistent with 2.747 min.
The LC analysis method was the same as that in step (2) of example 1.

Claims (10)

1.一种邻氟三氟甲苯的制备方法，其特征在于，其包括以下步骤：在有机溶剂中，将邻硝基三氟甲苯和氟化盐进行如下所示的脱硝氟代反应，得到邻氟三氟甲苯；1. a preparation method of o-fluorotrifluorotoluene, is characterized in that, it may further comprise the steps: in organic solvent, o-nitrotrifluorotoluene and fluoride salt are carried out the denitration fluorination reaction shown below, obtain o-nitrotrifluorotoluene Fluorotrifluorotoluene;
Figure FDA0003316572640000011
Figure FDA0003316572640000011
 2.如权利要求1所述的邻氟三氟甲苯的制备方法，其特征在于，所述的脱硝氟代反应满足下述条件中的一个或多个：2. the preparation method of o-fluorotoluene as claimed in claim 1, is characterized in that, described denitration fluorination reaction satisfies one or more in following conditions: 条件1，所述有机溶剂为非质子极性溶剂；所述非质子极性溶剂可为酮类溶剂、醚类溶剂、酰胺类溶剂和砜类溶剂中的一种或多种；所述酮类溶剂优选为丙酮；所述醚类溶剂优选为四氢呋喃；所述酰胺类溶剂优选为N,N-二甲基甲酰胺、N,N-二甲基乙酰胺、N-甲基吡咯烷酮和六甲基磷酰胺中的一种或多种；所述砜类溶剂优选为二甲基亚砜和/或环丁砜；Condition 1, the organic solvent is an aprotic polar solvent; the aprotic polar solvent can be one or more of ketone solvents, ether solvents, amide solvents and sulfone solvents; the ketones The solvent is preferably acetone; the ether solvent is preferably tetrahydrofuran; the amide solvent is preferably N,N-dimethylformamide, N,N-dimethylacetamide, N-methylpyrrolidone and hexamethylidene One or more of phosphoramide; the sulfone solvent is preferably dimethyl sulfoxide and/or sulfolane; 条件2，所述的氟化盐为氟化钠、氟化钾、氟化铯、四甲基氟化铵和四丁基氟化铵中的一种或多种；Condition 2, described fluoride salt is one or more in sodium fluoride, potassium fluoride, cesium fluoride, tetramethylammonium fluoride and tetrabutylammonium fluoride; 条件3，所述的邻硝基三氟甲苯与所述的有机溶剂的摩尔体积为1～3mol/L；Condition 3, the molar volume of described o-nitrotoluene and described organic solvent is 1～3mol/L; 条件4，所述的氟化盐与所述的邻硝基三氟甲苯的摩尔比为1.0～2.5:1；Condition 4, the molar ratio of the fluoride salt to the o-nitrotoluene trifluorotoluene is 1.0 to 2.5:1; 条件5，所述反应的反应温度为25～250℃。Condition 5, the reaction temperature of the reaction is 25-250°C. 3.如权利要求2所述的邻氟三氟甲苯的制备方法，其特征在于，所述的脱硝氟代反应满足下述条件中的一个或多个：3. the preparation method of o-fluorotoluene as claimed in claim 2, is characterized in that, described denitration fluorination reaction satisfies one or more in following conditions: 条件1，所述有机溶剂为N,N-二甲基甲酰胺和/或环丁砜；Condition 1, the organic solvent is N,N-dimethylformamide and/or sulfolane; 条件2，所述的氟化盐为四甲基氟化铵和/或氟化钾；Condition 2, described fluoride salt is tetramethylammonium fluoride and/or potassium fluoride; 条件3，所述的邻硝基三氟甲苯与所述的有机溶剂的摩尔体积为2～2.5mol/L；Condition 3, the molar volume of the o-nitrotoluene and the organic solvent is 2 to 2.5 mol/L; 条件4，所述的氟化盐与所述的邻硝基三氟甲苯的摩尔比为1.3～2.0:1；Condition 4, the molar ratio of the fluoride salt and the o-nitrotoluene trifluorotoluene is 1.3～2.0:1; 条件5，所述反应的反应温度为110℃～210℃。Condition 5, the reaction temperature of the reaction is 110°C to 210°C. 4.一种邻三氟甲基苯腈的制备方法，其特征在于，其包括如下步骤：4. a preparation method of o-trifluoromethyl benzonitrile, is characterized in that, it comprises the steps: (1)按照如权利要求1～3任一项所述的邻氟三氟甲苯的制备方法，制备得到邻氟三氟甲苯；(1) according to the preparation method of o-fluorotrifluorotoluene as described in any one of claims 1～3, prepare o-fluorotrifluorotoluene; (2)在有机溶剂中，将邻氟三氟甲苯和氰基化试剂进行如下所示的脱氟氰代反应，得到邻三氟甲基苯腈；(2) in an organic solvent, o-fluorotrifluorotoluene and a cyanating reagent are carried out to the defluorocyanation reaction shown below to obtain o-trifluoromethyl benzonitrile;
Figure FDA0003316572640000021
Figure FDA0003316572640000021
 5.如权利要求4所述的邻三氟甲基苯腈的制备方法，其特征在于，所述的脱氟氰代反应满足下述条件中的一个或多个：5. the preparation method of o-trifluoromethyl benzonitrile as claimed in claim 4, is characterized in that, described defluorocyanation reaction satisfies one or more in following conditions: 条件1，所述有机溶剂为非质子极性溶剂；所述非质子极性溶剂可为酮类溶剂、醚类溶剂、酰胺类溶剂和砜类溶剂中的一种或多种；所述酮类溶剂优选为丙酮；所述醚类溶剂优选为四氢呋喃；所述酰胺类溶剂优选为N,N-二甲基甲酰胺、N,N-二甲基乙酰胺、N-甲基吡咯烷酮和六甲基磷酰胺中的一种或多种；所述砜类溶剂优选为二甲基亚砜和/或环丁砜；Condition 1, the organic solvent is an aprotic polar solvent; the aprotic polar solvent can be one or more of ketone solvents, ether solvents, amide solvents and sulfone solvents; the ketones The solvent is preferably acetone; the ether solvent is preferably tetrahydrofuran; the amide solvent is preferably N,N-dimethylformamide, N,N-dimethylacetamide, N-methylpyrrolidone and hexamethylidene One or more of phosphoramide; the sulfone solvent is preferably dimethyl sulfoxide and/or sulfolane; 条件2，所述的氰基化试剂为氰化钠或氰化钾；Condition 2, described cyanation reagent is sodium cyanide or potassium cyanide; 条件3，所述的邻氟三氟甲苯与所述的有机溶剂的摩尔体积为1～3mol/L；Condition 3, the molar volume of the o-fluorotrifluorotoluene and the organic solvent is 1 to 3 mol/L; 条件4，所述的氰基化试剂与所述的邻氟三氟甲苯的摩尔比为1.0～2.0:1；Condition 4, the molar ratio of the cyanating reagent to the o-fluorotrifluorotoluene is 1.0 to 2.0:1; 条件5，所述反应的反应温度为50～200℃。Condition 5, the reaction temperature of the reaction is 50-200°C. 6.如权利要求5所述的邻三氟甲基苯腈的制备方法，其特征在于，所述的脱氟氰代反应满足下述条件中的一个或多个：6. the preparation method of o-trifluoromethyl benzonitrile as claimed in claim 5, is characterized in that, described defluorocyanation reaction satisfies one or more in following conditions: 条件1，所述有机溶剂为N,N-二甲基甲酰胺；Condition 1, the organic solvent is N,N-dimethylformamide; 条件2，所述的邻氟三氟甲苯与所述的有机溶剂的摩尔体积为2～2.5mol/L；Condition 2, the molar volume of the o-fluorotrifluorotoluene and the organic solvent is 2 to 2.5 mol/L; 条件3，所述的氰基化试剂与所述的邻氟三氟甲苯的摩尔比为1.1～1.6:1；Condition 3, the molar ratio of the cyanating reagent to the o-fluorotrifluorotoluene is 1.1 to 1.6:1; 条件4，所述反应的反应温度为90℃～120℃，例如100℃。Condition 4, the reaction temperature of the reaction is 90°C to 120°C, for example, 100°C. 7.一种邻三氟甲基苯甲酰胺的制备方法，其特征在于，其包括如下步骤：7. a preparation method of o-trifluoromethylbenzamide, is characterized in that, it comprises the steps: (1)按照如权利要求4～6任一项所述的邻三氟甲基苯腈的制备方法制备得到邻三氟甲基苯腈；(1) prepare o-trifluoromethyl benzonitrile according to the preparation method of o-trifluoromethyl benzonitrile as described in any one of claims 4 to 6; (2)在溶剂中，在碱存在下，将邻三氟甲基苯腈、过氧化氢进行如下所示的水解反应，得到邻三氟甲基苯甲酰胺；(2) in a solvent, in the presence of a base, o-trifluoromethyl benzonitrile and hydrogen peroxide are carried out the hydrolysis reaction shown below to obtain o-trifluoromethyl benzamide;
Figure FDA0003316572640000031
Figure FDA0003316572640000031
 8.如权利要求7所述的邻三氟甲基苯甲酰胺的制备方法，其特征在于，所述的水解反应满足下述条件中的一个或多个：8. the preparation method of o-trifluoromethylbenzamide as claimed in claim 7, is characterized in that, described hydrolysis reaction satisfies one or more in following condition: 条件1，所述的过氧化氢质量浓度为27％～50％，例如30％；Condition 1, the hydrogen peroxide mass concentration is 27% to 50%, such as 30%; 条件2，所述的过氧化氢与邻三氟甲基苯腈的摩尔比为2.0～3.0:1，例如2.5～2.8:1；Condition 2, the molar ratio of the hydrogen peroxide to o-trifluoromethyl benzonitrile is 2.0 to 3.0:1, for example, 2.5 to 2.8:1; 条件3，所述的碱为碳酸钠、碳酸钾、氢氧化钠和氢氧化钾中的一种，例如氢氧化钠；Condition 3, described alkali is a kind of in sodium carbonate, potassium carbonate, sodium hydroxide and potassium hydroxide, for example sodium hydroxide; 条件4，所述反应的反应液pH为10～13，例如11～12；Condition 4, the pH of the reaction solution is 10-13, for example, 11-12; 条件5，所述反应的反应温度为30℃～90℃，例如40～50℃；Condition 5, the reaction temperature of the reaction is 30 to 90°C, for example, 40 to 50°C; 条件6，所述的溶剂为水；部分所述的溶剂可与所述的碱形成碱溶液使用；所述的碱溶液质量浓度优选为5％～30％，例如20％。Condition 6, the solvent is water; part of the solvent can be used with the alkali to form an alkaline solution; the mass concentration of the alkaline solution is preferably 5% to 30%, such as 20%. 9.一种邻三氟甲基苯甲酰胺的制备方法，其特征在于，其包括如下步骤：9. a preparation method of o-trifluoromethylbenzamide, is characterized in that, it comprises the steps: (1)在有机溶剂中，将邻氟三氟甲苯和氰基化试剂进行如下所示的脱氟氰代反应，得到邻三氟甲基苯腈；(1) in an organic solvent, o-fluorotrifluorotoluene and a cyanating reagent are carried out to the defluorocyanation reaction shown below to obtain o-trifluoromethyl benzonitrile;
Figure FDA0003316572640000032
Figure FDA0003316572640000032
 (2)在碱存在下，将邻三氟甲基苯腈、过氧化氢进行如下所示的水解反应；(2) in the presence of alkali, ortho-trifluoromethyl benzonitrile, hydrogen peroxide are carried out the hydrolysis reaction shown below;
Figure FDA0003316572640000041
Figure FDA0003316572640000041
 所述脱氟氰代反应的条件如权利要求4～6任一项所述；所述水解反应的条件如权利要求7或8所述。The conditions for the defluorocyanation reaction are as described in any one of claims 4 to 6; the conditions for the hydrolysis reaction are as described in claim 7 or 8. 10.一种邻三氟甲基苯腈的制备方法，其特征在于，其包括如下步骤：在有机溶剂中，将邻氟三氟甲苯和氰基化试剂进行如下所示的脱氟氰代反应，得到邻三氟甲基苯腈；10. a preparation method of o-trifluoromethyl benzonitrile, is characterized in that, it comprises the steps: in organic solvent, o-fluorotrifluorotoluene and cyanation reagent are carried out defluorocyanation reaction shown below , to obtain o-trifluoromethyl benzonitrile;
Figure FDA0003316572640000042
Figure FDA0003316572640000042
 所述脱氟氰代反应的条件如权利要求4～6任一项所述。The conditions of the defluorocyanation reaction are as described in any one of claims 4-6.
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