阅读说明：本技术 2-氟-6-(三氟甲基)苯甲酰胺的制备方法 (Preparation method of 2-fluoro-6- (trifluoromethyl) benzamide ) 是由 鲁光英 周跃辉 于 2021-01-12 设计创作，主要内容包括：本发明提供了一种2-氟-6-(三氟甲基)苯甲酰胺的制备方法,包括向2-氟-6-(三氟甲基)苯甲酸的有机溶液中加入缚酸剂和氯化剂,将2-氟-6-(三氟甲基)苯甲酸酰氯化后,再加入胺化剂,使2-氟-6-(三氟甲基)苯甲酰氯酰胺化的步骤。本发明提供的2-氟-6-(三氟甲基)苯甲酰胺的的制备方法步骤简单、质量上乘,收率高,纯度高,适宜于工业化生产。(The invention provides a preparation method of 2-fluoro-6- (trifluoromethyl) benzamide, which comprises the steps of adding an acid-binding agent and a chlorinating agent into an organic solution of 2-fluoro-6- (trifluoromethyl) benzoic acid, performing acyl chlorination on the 2-fluoro-6- (trifluoromethyl) benzoic acid, and then adding an aminating agent to amidate the 2-fluoro-6- (trifluoromethyl) benzoyl chloride. The preparation method of the 2-fluoro-6- (trifluoromethyl) benzamide provided by the invention has the advantages of simple steps, high quality, high yield and high purity, and is suitable for industrial production.)

A process for producing 2-fluoro-6- (trifluoromethyl) benzamide, characterized in that:

comprises the steps of adding an acid-binding agent and a chlorinating agent into an organic solution of 2-fluoro-6- (trifluoromethyl) benzoic acid, performing acyl chlorination on the 2-fluoro-6- (trifluoromethyl) benzoic acid, and then adding an aminating agent to amidate the 2-fluoro-6- (trifluoromethyl) benzoyl chloride.

2. The process for producing 2-fluoro-6- (trifluoromethyl) benzamide according to claim 1 wherein:

the organic solvent adopted by the organic solution comprises toluene;

the chlorinating agent comprises thionyl chloride;

the aminating agent comprises ammonia;

the acid-binding agent comprises N, N-dimethylformamide or N, N-dimethylacetamide.

3. The process for producing 2-fluoro-6- (trifluoromethyl) benzamide according to claim 2 wherein:

the equivalent ratio of the 2-fluoro-6- (trifluoromethyl) benzoic acid to the thionyl chloride is 1: 1.3-1.7.

4. The process for producing 2-fluoro-6- (trifluoromethyl) benzamide according to claim 2 wherein:

comprises the step of amidating 2-fluoro-6- (trifluoromethyl) benzoyl chloride by introducing ammonia gas after acylating chlorination of 2-fluoro-6- (trifluoromethyl) benzoic acid.

5. The process for producing 2-fluoro-6- (trifluoromethyl) benzamide according to claim 4 wherein:

comprises the step of acylating chlorination of 2-fluoro-6- (trifluoromethyl) benzoic acid, then introducing ammonia gas to ensure that the pH value of the reaction solution is 7-8, and amidating the 2-fluoro-6- (trifluoromethyl) benzoyl chloride.

6. The process for producing 2-fluoro-6- (trifluoromethyl) benzamide according to claim 1 wherein:

the temperature of the acyl chlorination is 70-90 ℃;

the temperature of the amidation is-5 to 50 ℃.

7. The process for producing 2-fluoro-6- (trifluoromethyl) benzamide according to claim 1 wherein:

further comprising the step of purifying the I;

the purification I comprises the steps of extracting by adopting organic ester and drying;

the organic ester comprises ethyl acetate.

8. The process for producing 2-fluoro-6- (trifluoromethyl) benzamide according to claim 1 wherein:

the preparation method of the 2-fluoro-6- (trifluoromethyl) benzoic acid comprises the step of oxidizing 2-fluoro-6- (trifluoromethyl) benzaldehyde.

9. The process for producing 2-fluoro-6- (trifluoromethyl) benzamide according to claim 6 wherein:

the oxidant used for the oxidation comprises potassium permanganate;

the equivalent ratio of the 2-fluoro-6- (trifluoromethyl) benzaldehyde to the potassium permanganate is 1: 1.2-1.5;

the temperature of the oxidation is 35-60 ℃.

10. The process for producing 2-fluoro-6- (trifluoromethyl) benzamide according to claim 7 wherein:

the preparation method of the 2-fluoro-6- (trifluoromethyl) benzoic acid further comprises the steps of adjusting the pH value to 1, extracting by adopting halogenated alkane and drying by adopting anhydrous sodium sulfate;

the halogenated alkane comprises dichloromethane.

Technical Field

The invention relates to the technical field of organic matter synthesis, in particular to a preparation method of a compound 2-fluoro-6- (trifluoromethyl) benzamide.

Background

Penoxsulam is a new generation of broad-spectrum herbicide for paddy fields developed by the American ceramic agricultural company (Dow AgroSciences), is mainly used for preventing and removing weeds in paddy fields, and is the variety with the widest weed control spectrum in the existing herbicide for paddy fields. Penoxsulam is effective against barnyard grass (including barnyard grass resistant to propanil, quinclorac and acetyl coa carboxylase), annual cyperaceae weeds, and a wide variety of broadleaf weeds, such as, for example, marigold (heteranaliosa), carp gut (Ecliptaprostrata), sesbania (sesbania aexaltata), japanese kohlrabi (commelinadiffusas), monochoria vaginalis (monochoriavalinalis), and the like, and has a good control effect. The duration of the drug property of the herbicide is as long as 30-60 days, and the harm of weeds in all seasons can be basically controlled by one-time application of the herbicide. Meanwhile, the herbicide can prevent and kill bensulfuron methyl weeds in rice fields, has residual activity on a plurality of broadleaf and cyperaceae weeds, barnyard grass and the like, and is the variety with the widest weed control spectrum in the current herbicides for the rice fields.

Penoxsulam is effective by inhibiting acetolactate synthase (ALS), which is a sulfonamide herbicide that is also a typical acetolactate synthase inhibitor, similar to sulfonylurea herbicides. It targets ALS, competes for enzyme binding sites, has no competition for matrix or cofactor, and is a mixed inhibitor involving pyruvate and thiamine pyrophosphate (TPP). The sulfonamide herbicide has the main structural form of triazolopyrimidine sulfonamide, and 6 varieties are dry-land herbicides which comprise flumetsulam, pyroxsulam, cloransulam, diclosulam, florasulam and penoxsulam. The flumetsulam is safe to soybean, corn, wheat, barley, pea, alfalfa, clover and the like, and has no adverse effect on the following crops. The pyroxsulam is used for preventing and controlling most of main broadleaf weeds in wheat, barley and rye fields after emergence, and can be used for preventing and controlling most of main broadleaf weeds in corn fields before and after emergence. The cloransulam methyl is mainly used for preventing and killing broad-leaved weeds before and after seedling in soybean fields, and has special effects on cocklebur, ragweed, split-leaf ragweed, sweet potato and piemarker. Diclosulam is a herbicide for soybean field. The florasulam is mainly used for preventing and killing broadleaf weeds in winter wheat fields after seedlings. Penoxsulam is a recently reported herbicide and is mainly used for preventing and killing weeds in paddy fields.

2-fluoro-6- (trifluoromethyl) benzamide is an important raw material for synthesizing penoxsulam, but related literature data are few at present, so that the search for a synthetic method of 2-fluoro-6- (trifluoromethyl) benzamide, which has simple steps and superior quality and is suitable for industrial production, becomes an urgent problem to be solved.

Disclosure of Invention

Aiming at the defects and problems of the prior art, the invention provides a preparation method of 2-fluoro-6- (trifluoromethyl) benzamide, aiming at solving the technical problems that: provides a preparation method of 2-fluoro-6- (trifluoromethyl) benzamide, which has high yield and good quality and is suitable for factory amplification production.

In order to achieve the purpose, the invention adopts the following technical means:

a process for preparing 2-fluoro-6- (trifluoromethyl) benzamide includes such steps as adding acid-binding agent and chlorinating agent to the organic solution of 2-fluoro-6- (trifluoromethyl) benzoic acid, acid chlorinating 2-fluoro-6- (trifluoromethyl) benzoic acid, adding aminating agent, and amidating 2-fluoro-6- (trifluoromethyl) benzoyl chloride.

Preferably, the organic solvent used for the organic solution comprises toluene.

Preferably, the chlorinating agent comprises thionyl chloride.

Preferably, the aminating agent comprises ammonia gas.

Preferably, the acid scavenger comprises N, N-dimethylformamide or N, N-dimethylacetamide.

Preferably, the equivalent ratio of the 2-fluoro-6- (trifluoromethyl) benzoic acid to the thionyl chloride is 1: 1.3-1.7.

Preferably, the preparation method of the 2-fluoro-6- (trifluoromethyl) benzamide comprises the step of amidating the 2-fluoro-6- (trifluoromethyl) benzoyl chloride by introducing ammonia gas after acylating chlorination of the 2-fluoro-6- (trifluoromethyl) benzoic acid.

Preferably, the method for preparing 2-fluoro-6- (trifluoromethyl) benzamide comprises the step of acylating chlorination of 2-fluoro-6- (trifluoromethyl) benzoic acid, then introducing ammonia gas to adjust the pH value of the reaction solution to 7-8, and amidating the 2-fluoro-6- (trifluoromethyl) benzoyl chloride.

Preferably, the temperature of the acyl chlorination is 70-90 ℃.

Preferably, the temperature of amidation is-5 to 50 ℃.

Preferably, the preparation method of the 2-fluoro-6- (trifluoromethyl) benzamide further comprises the step of purifying I.

Preferably, the purification I comprises the steps of extraction with an organic ester and drying.

Preferably, the organic ester comprises ethyl acetate.

Preferably, the method for preparing 2-fluoro-6- (trifluoromethyl) benzoic acid comprises a step of oxidizing 2-fluoro-6- (trifluoromethyl) benzaldehyde.

Preferably, the oxidizing agent used for the oxidation comprises potassium permanganate.

Preferably, the equivalent ratio of the 2-fluoro-6- (trifluoromethyl) benzaldehyde to the potassium permanganate is 1: 1.2-1.5.

Preferably, the temperature of the oxidation is 35-60 ℃.

Preferably, the preparation method of 2-fluoro-6- (trifluoromethyl) benzoic acid further comprises the steps of adjusting the pH value to 1, extracting by using halogenated alkane and drying by using anhydrous sodium sulfate.

The halogenated alkane comprises dichloromethane.

The reaction equation of the preparation method of the 2-fluoro-6- (trifluoromethyl) benzamide provided by the invention is as follows:

compared with the prior art, the invention has the following technical effects:

the preparation method of the 2-fluoro-6- (trifluoromethyl) benzamide provided by the invention has the advantages of simple steps, high quality, high yield and high purity, and is suitable for industrial production.

Drawings

In order to more clearly illustrate the technical solutions of the embodiments of the present invention, the drawings needed to be used in the embodiments will be briefly described below, it should be understood that the following drawings only illustrate some embodiments of the present invention and therefore should not be considered as limiting the scope, and for those skilled in the art, other related drawings can be obtained according to the drawings without inventive efforts.

FIG. 1 shows a gas chromatogram of 2-fluoro-6- (trifluoromethyl) benzamide prepared in example 2.

Detailed Description

The following describes embodiments of the present invention in detail. The embodiments described below with reference to the accompanying drawings are illustrative only for the purpose of explaining the present invention, and are not to be construed as limiting the present invention.

The invention provides a preparation method of 2-fluoro-6- (trifluoromethyl) benzamide, which comprises the following steps:

synthesis of Q1, 2-fluoro-6- (trifluoromethyl) benzoic acid: 2-fluoro-6- (trifluoromethyl) benzaldehyde is used as a raw material, and the 2-fluoro-6- (trifluoromethyl) benzoic acid is obtained through oxidation reaction, liquid separation, extraction and drying.

Synthesis of Q2, 2-fluoro-6- (trifluoromethyl) benzamide: catalyzing 2-fluoro-6- (trifluoromethyl) benzoic acid by a catalyst, reacting with thionyl chloride, slowly introducing ammonia gas, standing, separating liquid, extracting, pulping, and drying to obtain the 2-fluoro-6- (trifluoromethyl) benzamide.

The technical solution of the present invention is illustrated by the following specific examples:

example 1

Synthesis of 2-fluoro-6- (trifluoromethyl) benzoic acid

Dissolving 5.13kg of potassium permanganate in water, adding the potassium permanganate into a reaction kettle, heating to 35 ℃, dropwise adding 4.8kg of 2-fluoro-6- (trifluoromethyl) benzaldehyde into the reaction kettle, controlling the reaction temperature to be 60 ℃, after the dropwise adding of the sample is finished, keeping the temperature at 50 ℃ for reaction for 1h, and monitoring the reaction process by adopting HPLC. After the reaction is finished, hydrochloric acid is added to adjust the pH value to 1, then liquid separation is carried out, organic layers are collected, a water layer is extracted twice by dichloromethane, the organic layers are combined, finally, the organic layers are dried by anhydrous sodium sulfate and then concentrated under reduced pressure, and 4.25kg of 2-fluoro-6- (trifluoromethyl) benzoic acid is obtained.

The 2-fluoro-6- (trifluoromethyl) benzoic acid prepared in example 1 was tested to have a purity of greater than 99.0% and a yield of 81.7%.

Example 2

Synthesis of 2-fluoro-6- (trifluoromethyl) benzoic acid

Dissolving 5.13kg of potassium permanganate in water, adding the potassium permanganate into a reaction kettle, heating to 40 ℃, dropwise adding 4.8kg of 2-fluoro-6- (trifluoromethyl) benzaldehyde into the reaction kettle, controlling the reaction temperature to be 60 ℃, after the dropwise adding of the sample is finished, keeping the temperature at 50 ℃ for reaction for 1h, and monitoring the reaction process by adopting HPLC. After the reaction is finished, hydrochloric acid is added to adjust the pH value to 1, then liquid separation is carried out, organic layers are collected, a water layer is extracted twice by dichloromethane, the organic layers are combined, finally, the organic layers are dried by anhydrous sodium sulfate and then concentrated under reduced pressure, and 4.4kg of 2-fluoro-6- (trifluoromethyl) benzoic acid is obtained.

The 2-fluoro-6- (trifluoromethyl) benzoic acid prepared in example 2 was tested to have a purity of greater than 99.0% and a yield of 84.6%.

Example 3

Synthesis of 2-fluoro-6- (trifluoromethyl) benzoic acid

Dissolving 5.13kg of potassium permanganate in water, adding the potassium permanganate into a reaction kettle, heating to 45 ℃, dropwise adding 4.8kg of 2-fluoro-6-trifluoromethylbenzaldehyde into the reaction kettle, controlling the reaction temperature to be 60 ℃, after the dropwise adding of the sample is finished, keeping the temperature at 50 ℃ for reaction for 1h, and monitoring the reaction process by adopting HPLC. After the reaction is finished, hydrochloric acid is added to adjust the pH value to 1, then liquid separation is carried out, organic layers are collected, a water layer is extracted twice by dichloromethane, the organic layers are combined, finally, the organic layers are dried by anhydrous sodium sulfate and then concentrated under reduced pressure, and 4.5kg of 2-fluoro-6- (trifluoromethyl) benzoic acid is obtained.

The 2-fluoro-6- (trifluoromethyl) benzoic acid prepared in example 3 was tested to have a purity of greater than 99.0% and a yield of 86.5%.

Example 4

Synthesis of 2-fluoro-6- (trifluoromethyl) benzoic acid

Dissolving 5.13kg of potassium permanganate in water, adding the potassium permanganate into a reaction kettle, heating to 50 ℃, dropwise adding 4.8kg of 2-fluoro-6-trifluoromethylbenzaldehyde into the reaction kettle, controlling the reaction temperature to be 60 ℃, after the dropwise adding of the sample is finished, keeping the temperature at 50 ℃ for reaction for 1h, and monitoring the reaction process by adopting HPLC. After the reaction is finished, hydrochloric acid is added to adjust the pH value to 1, then liquid separation is carried out, organic layers are collected, a water layer is extracted twice by dichloromethane, the organic layers are combined, finally, the organic layers are dried by anhydrous sodium sulfate and then concentrated under reduced pressure, and 4.13kg of 2-fluoro-6- (trifluoromethyl) benzoic acid is obtained.

The 2-fluoro-6- (trifluoromethyl) benzoic acid prepared in example 4 was tested to have a purity of greater than 99.0% and a yield of 79.4%.

Example 5

Synthesis of 2-fluoro-6- (trifluoromethyl) benzoic acid

Dissolving 5.13kg of potassium permanganate in water, adding the potassium permanganate into a reaction kettle, heating to 35 ℃, dropwise adding 4.8kg of 2-fluoro-6-trifluoromethylbenzaldehyde into the reaction kettle, controlling the reaction temperature to be 5 ℃, keeping the temperature of 50 ℃ for reaction for 1h after the dropwise adding of the sample is finished, and monitoring the reaction process by adopting HPLC. After the reaction is finished, hydrochloric acid is added to adjust the pH value to 1, then liquid separation is carried out, organic layers are collected, a water layer is extracted twice by dichloromethane, the organic layers are combined, finally, the organic layers are dried by anhydrous sodium sulfate and then concentrated under reduced pressure, and 4.6kg of 2-fluoro-6- (trifluoromethyl) benzoic acid is obtained.

The 2-fluoro-6- (trifluoromethyl) benzoic acid prepared in example 5 was tested to have a purity of greater than 99.0% and a yield of 88.4%.

Example 6

Synthesis of 2-fluoro-6- (trifluoromethyl) benzamide

Heating 4.25kg of 2-fluoro-6- (trifluoromethyl) benzoic acid in 1.5L of toluene for dissolving, then adding 30ml of N, N-dimethylformamide as a catalyst, slowly dripping 3.40kg of thionyl chloride at 80 ℃, then carrying out heat preservation reaction for 2-4 h, carrying out reduced pressure concentration to remove residual solvent, then cooling to-5 ℃, slowly introducing ammonia gas, controlling the temperature not to exceed 50 ℃, and introducing the ammonia gas until the pH value of the reaction solution is 8, thus completing the reaction. Dissolving in water, standing, separating, extracting water phase with 2L ethyl acetate, mixing organic phases, rinsing with dichloromethane to obtain white solid, pulping, desalting, filtering to obtain wet product, and drying to obtain 3.77kg 2-fluoro-6- (trifluoromethyl) benzamide.

The 2-fluoro-6- (trifluoromethyl) benzamide prepared in example 6 was tested to have a purity of greater than 99.0% and a yield of 89.1%.

Example 7

Synthesis of 2-fluoro-6- (trifluoromethyl) benzamide

Heating 4.25kg of 2-fluoro-6- (trifluoromethyl) benzoic acid in 1.5L of toluene for dissolving, then adding 35ml of N, N-dimethylformamide as a catalyst, slowly dripping 3.40kg of thionyl chloride at 80 ℃, then carrying out heat preservation reaction for 2-4 h, carrying out reduced pressure concentration to remove residual solvent, then cooling to-5 ℃, slowly introducing ammonia gas, controlling the temperature not to exceed 50 ℃, and introducing the ammonia gas until the pH value of the reaction solution is 8, thus completing the reaction. Dissolving in water, standing, separating, extracting water phase with 2L ethyl acetate, mixing organic phases, rinsing with dichloromethane to obtain white solid, pulping, desalting, filtering to obtain wet product, and drying to obtain 3.65kg 2-fluoro-6- (trifluoromethyl) benzamide.

The 2-fluoro-6- (trifluoromethyl) benzamide prepared in example 7 was tested to have a purity of greater than 99.0% and a yield of 86.2%.

Example 8

Synthesis of 2-fluoro-6- (trifluoromethyl) benzamide

Heating 4.25kg of 2-fluoro-6- (trifluoromethyl) benzoic acid in 1.5L of toluene for dissolving, then adding 40ml of N, N-dimethylformamide as a catalyst, slowly dripping 3.40kg of thionyl chloride at 80 ℃, then carrying out heat preservation reaction for 2-4 h, carrying out reduced pressure concentration to remove residual solvent, then cooling to-5 ℃, slowly introducing ammonia gas, controlling the temperature not to exceed 50 ℃, and introducing the ammonia gas until the pH value of the reaction solution is 8, thus completing the reaction. Dissolving in water, standing, separating, extracting water phase with 2L ethyl acetate, mixing organic phases, rinsing with dichloromethane to obtain white solid, pulping, desalting, filtering to obtain wet product, and drying to obtain 3.80kg 2-fluoro-6- (trifluoromethyl) benzamide.

The 2-fluoro-6- (trifluoromethyl) benzamide prepared in example 8 was tested to have a purity of greater than 99.0% and a yield of 89.8%.

Example 9

Synthesis of 2-fluoro-6- (trifluoromethyl) benzamide

Heating 4.25kg of 2-fluoro-6- (trifluoromethyl) benzoic acid in 1.5L of toluene for dissolving, then adding 25ml of N, N-dimethylformamide as a catalyst, slowly dripping 3.40kg of thionyl chloride at 80 ℃, then carrying out heat preservation reaction for 2-4 h, carrying out reduced pressure concentration to remove residual solvent, then cooling to-5 ℃, slowly introducing ammonia gas, controlling the temperature not to exceed 50 ℃, and introducing the ammonia gas until the pH value of the reaction solution is 8, thus completing the reaction. Dissolving in water, standing, separating, extracting water phase with 2L ethyl acetate, mixing organic phases, rinsing with dichloromethane to obtain white solid, pulping, desalting, filtering to obtain wet product, and drying to obtain 3.54kg 2-fluoro-6- (trifluoromethyl) benzamide.

The 2-fluoro-6- (trifluoromethyl) benzamide prepared in example 9 was tested to have a purity of greater than 99.0% and a yield of 83.7%.

Example 10

Synthesis of 2-fluoro-6- (trifluoromethyl) benzamide

Heating 4.25kg of 2-fluoro-6- (trifluoromethyl) benzoic acid in 1.5L of toluene for dissolving, then adding 20ml of N, N-dimethylformamide as a catalyst, slowly dropwise adding 3.40kg of thionyl chloride at 80 ℃, then carrying out heat preservation reaction for 2-4 h, carrying out reduced pressure concentration to remove residual solvent, then cooling to-5 ℃, slowly introducing ammonia gas, controlling the temperature not to exceed 50 ℃, and introducing the ammonia gas until the pH value of the reaction solution is 8, thus completing the reaction. Dissolving in water, standing, separating, extracting water phase with 2L ethyl acetate, mixing organic phases, rinsing with dichloromethane to obtain white solid, pulping, desalting, filtering to obtain wet product, and drying to obtain 3.75kg 2-fluoro-6- (trifluoromethyl) benzamide.

The 2-fluoro-6- (trifluoromethyl) benzamide prepared in example 10 was tested to have a purity of greater than 99.0% and a yield of 88.6%.

Example 11

Synthesis of 2-fluoro-6- (trifluoromethyl) benzamide

Heating 4.25kg of 2-fluoro-6- (trifluoromethyl) benzoic acid in 1.5L of toluene for dissolving, then adding 35ml of N, N-dimethylacetamide as a catalyst, slowly dripping 3.40kg of thionyl chloride at 80 ℃, then carrying out heat preservation reaction for 2-4 h, carrying out reduced pressure concentration to remove residual solvent, then cooling to-5 ℃, slowly introducing ammonia gas, controlling the temperature not to exceed 50 ℃, and introducing the ammonia gas until the pH value of the reaction solution is 8, thus completing the reaction. Dissolving in water, standing, separating, extracting water phase with 2L ethyl acetate, mixing organic phases, rinsing with dichloromethane to obtain white solid, pulping, desalting, filtering to obtain wet product, and drying to obtain 3.96kg 2-fluoro-6- (trifluoromethyl) benzamide.

The 2-fluoro-6- (trifluoromethyl) benzamide prepared in example 11 was tested to have a purity of greater than 99.0% and a yield of 93.6%.

Example 12

Synthesis of 2-fluoro-6- (trifluoromethyl) benzamide

Heating 4.25kg of 2-fluoro-6- (trifluoromethyl) benzoic acid in 1.5L of toluene for dissolving, then adding 40ml of N, N-dimethylacetamide as a catalyst, slowly dripping 3.40kg of thionyl chloride at 80 ℃, then carrying out heat preservation reaction for 2-4 h, carrying out reduced pressure concentration to remove residual solvent, then cooling to-5 ℃, slowly introducing ammonia gas, controlling the temperature not to exceed 50 ℃, and introducing the ammonia gas until the pH value of the reaction solution is 8, thus completing the reaction. Dissolving in water, standing, separating, extracting water phase with 2L ethyl acetate, mixing organic phases, rinsing with dichloromethane to obtain white solid, pulping, desalting, filtering to obtain wet product, and drying to obtain 3.87kg 2-fluoro-6- (trifluoromethyl) benzamide.

The 2-fluoro-6- (trifluoromethyl) benzamide prepared in example 12 was tested to have a purity of greater than 99.0% and a yield of 91.4%.

Example 13

Synthesis of 2-fluoro-6- (trifluoromethyl) benzamide

Heating 4.25kg of 2-fluoro-6- (trifluoromethyl) benzoic acid in 1.5L of toluene for dissolving, then adding 30ml of N, N-dimethylacetamide as a catalyst, slowly dripping 3.40kg of thionyl chloride at 80 ℃, then carrying out heat preservation reaction for 2-4 h, carrying out reduced pressure concentration to remove residual solvent, then cooling to-5 ℃, slowly introducing ammonia gas, controlling the temperature not to exceed 50 ℃, and introducing the ammonia gas until the pH value of the reaction solution is 8, thus completing the reaction. Dissolving in water, standing, separating, extracting water phase with 2L ethyl acetate, mixing organic phases, rinsing with dichloromethane to obtain white solid, pulping, desalting, filtering to obtain wet product, and drying to obtain 3.66kg 2-fluoro-6- (trifluoromethyl) benzamide.

The 2-fluoro-6- (trifluoromethyl) benzamide prepared in example 13 was tested to have a purity of greater than 99.0% and a yield of 86.5%.

Example 14

Synthesis of 2-fluoro-6- (trifluoromethyl) benzamide

Heating 4.25kg of 2-fluoro-6- (trifluoromethyl) benzoic acid in 1.5L of toluene for dissolving, then adding 25ml of N, N-dimethylacetamide as a catalyst, slowly dripping 3.40kg of thionyl chloride at 80 ℃, then carrying out heat preservation reaction for 2-4 h, carrying out reduced pressure concentration to remove residual solvent, then cooling to-5 ℃, slowly introducing ammonia gas, controlling the temperature not to exceed 50 ℃, and introducing the ammonia gas until the pH value of the reaction solution is 8, thus completing the reaction. Dissolving in water, standing, separating, extracting water phase with 2L ethyl acetate, mixing organic phases, rinsing with dichloromethane to obtain white solid, pulping, desalting, filtering to obtain wet product, and drying to obtain 3.82kg 2-fluoro-6- (trifluoromethyl) benzamide.

The 2-fluoro-6- (trifluoromethyl) benzamide prepared in example 14 was tested to have a purity of greater than 99.0% and a yield of 90.3%.

Although embodiments of the present invention have been shown and described above, it is understood that the above embodiments are exemplary and should not be construed as limiting the present invention, and that variations, modifications, substitutions and alterations can be made to the above embodiments by those of ordinary skill in the art within the scope of the present invention.