A process for the preparation of 2-amino-5-chloro-N,3-dimethylbenzamide

Abstract

This invention relates to a method for preparing 2-amino-5-chloro-N,3-dimethylbenzamide, belonging to the technical field of organic synthesis. The preparation method involves reacting 4-chloro-2-methylaniline as a raw material with methyl isocyanate under the action of a Lewis acid to obtain 2-amino-5-chloro-N,3-dimethylbenzamide; wherein the Lewis acid is one of ZnCl2, AlCl3, BCl3, or FeCl3. In the preparation method of 2-amino-5-chloro-N,3-dimethylbenzamide provided by this invention, the product can be obtained in one step under the catalysis of a specific catalyst. The reaction conditions of this invention are mild, the single-step product yield is high, and it is suitable for industrial production.

Description

Technical Field

[0001] This invention relates to the field of organic synthesis, specifically to a method for preparing 2-amino-5-chloro-N,3-dimethylbenzamide. Background Technology

[0002] Chlorantraniliprole (Chinese name: Kangkuan) is a novel, highly effective, and low-toxicity o-formylaminobenzamide insecticide developed by DuPont in 2000. It belongs to the ryanodine receptor inhibitor class of insecticides. It is safe for mammals and exhibits high efficiency, broad spectrum, and a novel mechanism of action, possessing broad market potential and prospects. 2-Amino-5-chloro-N,3-dimethylbenzamide (Kamine) is a key intermediate in the synthesis of chlorantraniliprole. Numerous literature reports on the synthesis process of 2-amino-5-chloro-N,3-dimethylbenzamide. Several specific synthetic routes are listed below: 1. Patent CN114621130B discloses a method for preparing 2-amino-5-chloro-N,3-dimethylbenzamide. The method uses o-toluidine as a raw material, reacting it with trichloroacetaldehyde and hydroxylamine hydrochloride, followed by cyclization with concentrated sulfuric acid to prepare 7-methylindigo. Then, ring-opening is achieved through oxidation with sodium hydroxide and hydrogen peroxide, followed by chlorination and formamidation reactions to obtain 2-amino-5-chloro-N,3-dimethylbenzamide. The specific preparation route is as follows: .

[0003] However, the above methods have problems such as high cost of trichloroacetaldehyde raw materials, low yield of cyclization reaction using concentrated sulfuric acid, and large amount of waste salt, making it difficult to scale up production in actual industry.

[0004] 2. Patent CN111517975A reports a method for preparing 2-amino-5-chloro-N,3-dimethylbenzamide from 2-nitro-3-methylbenzoic acid via hydrogenation reduction, chlorination, and formamidation. The specific preparation route is as follows: .

[0005] However, the above methods use pressurized hydrogen reduction, which poses safety hazards during the reaction. Chlorination uses chlorine gas, a highly toxic chemical that is also highly corrosive to equipment. Overall, these methods are also detrimental to industrial production.

[0006] 3. Patent CN101492387B uses methyl 3-methyl-2-nitrobenzene as a raw material, first reacting it with methylamine to prepare 3-methyl-2-nitrobenzeneamide; then using Fe / H + The nitro group was reduced to give 3-methyl-2-aminobenzamide; finally, chlorination with sulfonyl chloride was performed to give 2-amino-5-chloro-N,3-dimethylbenzamide. The specific preparation route is as follows: .

[0007] The above reaction used iron powder for reduction of nitro groups, resulting in a large amount of iron sludge and ferric hydroxide colloid produced by hydrolysis in the reaction solution, making solid-liquid separation difficult.

[0008] Other patent reports exist, such as: Patent CN115583895A, which describes a process using 3-methyl-5-chlorobenzoic acid as a raw material, involving nitration, chlorination, methylamination, and final reduction of the nitro group to obtain the target product; and Patent CN111517975A, which describes a process using 2-nitro-3-methylbenzoic acid as a raw material, involving hydrogenation reduction, chlorination, esterification, and ammonolysis to obtain the target product. These methods require acidic catalysts for ester synthesis, such as highly corrosive and polluting organic / inorganic acids like concentrated sulfuric acid and p-toluenesulfonic acid, and these reactions generally have long reaction times.

[0009] In summary, a method conducive to industrial production is needed for the synthesis of 2-amino-5-chloro-N,3-dimethylbenzamide. Summary of the Invention

[0010] To address the technical problems existing in the preparation of 2-amino-5-chloro-N,3-dimethylbenzamide, such as low reaction yield, safety risks, and difficulty in handling the reaction process, this invention provides a method for preparing 2-amino-5-chloro-N,3-dimethylbenzamide to solve the above problems.

[0011] The technical solution of this invention is as follows: A method for preparing 2-amino-5-chloro-N,3-dimethylbenzamide involves reacting 4-chloro-2-methylaniline with methyl isocyanate under the action of a Lewis acid to obtain 2-amino-5-chloro-N,3-dimethylbenzamide. The reaction formula is as follows: .

[0012] This invention relates to a rearrangement reaction, the specific reaction mechanism of which is as follows, taking AlCl3 catalysis as an example: ; Furthermore, the Lewis acid is one of ZnCl2, AlCl3, BCl3, or FeCl3. These Lewis acids, after dissolving in the reaction solution, are not easily hydrolyzed, and therefore are less prone to catalyst deactivation during the catalytic reaction.

[0013] Furthermore, the Lewis acid is AlCl3.

[0014] Includes the following steps: 4-Chloro-2-methylaniline was added to a solvent, and the reaction solution was cooled to -5℃ to 5℃ under nitrogen protection. Then, methyl isocyanate was added to the reaction solution, and Lewis acid was added to the reaction solution at -5℃ to 5℃. After the reaction was maintained at this temperature for 15 min, the temperature was raised to 10℃ to 40℃. After the reaction was completed, water was added to quench the reaction solution, and the solution was extracted with dichloromethane. The organic phase was washed with water, dried, and the solvent was removed to obtain 2-amino-5-chloro-N,3-dimethylbenzamide.

[0015] Furthermore, the molar ratio of 4-chloro-2-methylaniline to Lewis acid is 1:1 to 3. Within this range, the Lewis acid can fully activate the reaction intermediate, promoting efficient rearrangement reaction. When the ratio is too low, insufficient substrate activation leads to a slower reaction and lower conversion rate. When the ratio is too high, excessive substrate complexation, product decomposition, and emulsification during post-processing are likely to occur.

[0016] Furthermore, the molar ratio of 4-chloro-2-methylaniline to Lewis acid is 1:1.2. A 1.2 equivalent ratio achieves an optimal balance between catalytic efficiency, reaction selectivity, and post-processing difficulty, resulting in the best yield and purity.

[0017] Furthermore, the molar ratio of 4-chloro-2-methylaniline to methyl isocyanate is 1:1~2.

[0018] Furthermore, the molar ratio of 4-chloro-2-methylaniline to methyl isocyanate is 1:1.02.

[0019] Furthermore, it also includes a process for refining 2-amino-5-chloro-N,3-dimethylbenzamide, wherein recrystallization is performed using 95% ethanol.

[0020] Furthermore, the solvent is dichloromethane, 1,2-dichloroethane, chloroform, benzene, or toluene. These solvents exhibit good solubility for the substrate and excellent compatibility with Lewis acids, ensuring a homogeneous reaction system and high mass transfer efficiency.

[0021] Furthermore, the solvent is dichloromethane.

[0022] The beneficial effects of this invention are as follows: The method for preparing 2-amino-5-chloro-N,3-dimethylbenzamide provided by this invention allows for the product to be obtained in one step under the catalysis of a specific catalyst. This invention features mild reaction conditions, high single-step product yield, and is suitable for industrial production. Detailed Implementation

[0023] To enable those skilled in the art to better understand the technical solutions of this invention, the technical solutions in the embodiments of this invention will be clearly and completely described below. Obviously, the described embodiments are only some embodiments of this invention, and not all embodiments. Based on the embodiments of this invention, all other embodiments obtained by those skilled in the art without creative effort should fall within the scope of protection of this invention.

[0024] Example 1 1.41 g (10 mmol) of 4-chloro-2-methylaniline was weighed and added to 10 mL of dichloromethane. The reaction solution was cooled to 0 °C under nitrogen protection. Then, 0.58 g of methyl isocyanate (12 mmol) was added to the reaction solution, and the mixture was stirred for 15 min after the addition was complete. Then, 1.6 g of anhydrous aluminum trichloride (12 mmol) was slowly added to the reaction solution at 0 °C. After the addition was complete, the reaction was maintained at this temperature for 15 min, and then the reaction solution was heated to 25 °C and reacted for 10 h. HPLC analysis was performed to confirm that the 4-chloro-2-methylaniline reaction was complete. 5 mL of water was added to the reaction solution, and the reaction was quenched by stirring for 20 min. The reaction solution was then extracted three times with 5 mL of dichloromethane each time. The organic phases were combined, dried over anhydrous sodium sulfate, and distilled under reduced pressure to obtain crude 2-amino-5-chloro-N,3-dimethylbenzamide. The crude product was recrystallized from 6 ml of 95% ethanol to obtain 1.910 g of 2-amino-5-chloro-N,3-dimethylbenzamide, with a yield of 96.46% and an HPLC purity of 99.5% (area normalized).

[0025] 1 H-NMR (400 MHz, Chloroform-d): δ2.08(s,3H), 2.72(d, J=4.5Hz, 3H),6.34(br s, 2H), 7.12(d, J=2.4Hz, 1H), 7.39(d, J=2.4Hz, 1H), 8.31(br d,1H).

[0026] MS: 199 (M+H) + .

[0027] Example 2 1.41 g (10 mmol) of 4-chloro-2-methylaniline was weighed and added to 10 mL of dichloromethane. The reaction solution was cooled to 0 °C under nitrogen protection. Then, 0.58 g of methyl isocyanate (12 mmol) was added to the reaction solution, and the mixture was stirred for 15 min after the addition was complete. Next, 1.64 g of zinc chloride (12 mmol) was slowly added to the reaction solution at 0 °C, and the mixture was kept at this temperature for 15 min after the addition was complete. The reaction solution was then heated to 25 °C and reacted for 20 h. HPLC analysis was performed to confirm the complete reaction of 4-chloro-2-methylaniline. 5 mL of water was added to the reaction solution, and the reaction was quenched by stirring for 20 min. The reaction solution was then extracted three times with 5 mL of dichloromethane each time. The organic phases were combined, dried over anhydrous sodium sulfate, and distilled under reduced pressure to obtain crude 2-amino-5-chloro-N,3-dimethylbenzamide. The crude product was recrystallized from 6 ml of 95% ethanol to obtain 1.489 g of 2-amino-5-chloro-N,3-dimethylbenzamide, with a yield of 75.2% and an HPLC purity of 96.1% (area normalized).

[0028] Example 3 1.41 g (10 mmol) of 4-chloro-2-methylaniline was weighed and added to 10 mL of dichloromethane. The reaction solution was cooled to 0 °C under nitrogen protection. Then, 0.58 g of methyl isocyanate (12 mmol) was added to the reaction solution, and the mixture was stirred for 15 min after the addition was complete. Next, 1.95 g of ferric chloride (12 mmol) was slowly added to the reaction solution at 0 °C, and the mixture was kept at this temperature for 15 min after the addition was complete. The reaction solution was then heated to 25 °C and reacted for 20 h. HPLC analysis was performed to confirm the complete reaction of 4-chloro-2-methylaniline. 5 mL of water was added to the reaction solution, and the reaction was quenched by stirring for 20 min. The reaction solution was then extracted three times with 5 mL of dichloromethane each time. The organic phases were combined, dried over anhydrous sodium sulfate, and distilled under reduced pressure to obtain crude 2-amino-5-chloro-N,3-dimethylbenzamide. The crude product was recrystallized from 6 ml of 95% ethanol to obtain 1.368 g of 2-amino-5-chloro-N,3-dimethylbenzamide, with a yield of 69.1% and an HPLC purity of 95.2% (area normalized).

[0029] Example 4 1.41 g (10 mmol) of 4-chloro-2-methylaniline was weighed and added to 10 mL of dichloromethane. The reaction solution was cooled to 0 °C under nitrogen protection. Then, 0.58 g (12 mmol) of methyl isocyanate was added to the reaction solution, and the mixture was stirred for 15 min after the addition was complete. Next, 12 mL of 1 mol / L boron trichloride diethyl ether solution (12 mmol) was slowly added to the reaction solution at 0 °C. After the addition was complete, the reaction was maintained at this temperature for 15 min, and then the reaction solution was heated to 25 °C and reacted for 15 h. HPLC analysis was performed to confirm the complete reaction of 4-chloro-2-methylaniline. 5 mL of water was added to the reaction solution, and the reaction was quenched by stirring for 20 min. The reaction solution was then extracted three times with 5 mL of dichloromethane each time. The organic phases were combined, dried over anhydrous sodium sulfate, and distilled under reduced pressure to obtain crude 2-amino-5-chloro-N,3-dimethylbenzamide. The crude product was recrystallized from 6 ml of 95% ethanol to obtain 1.39 g of 2-amino-5-chloro-N,3-dimethylbenzamide, with a yield of 93.2% and an HPLC purity of 97.8% (area normalized).

[0030] Example 5 1.41 g (10 mmol) of 4-chloro-2-methylaniline was weighed and added to 10 mL of dichloromethane. The reaction solution was cooled to 0 °C under nitrogen protection. Then, 0.58 g of methyl isocyanate (12 mmol) was added to the reaction solution, and the mixture was stirred for 15 min after the addition was complete. Next, 1.33 g of anhydrous aluminum trichloride (10 mmol) was slowly added to the reaction solution at 0 °C, and the mixture was kept at this temperature for 15 min after the addition was complete. The reaction solution was then heated to 25 °C and reacted for 18 h. HPLC analysis confirmed that the 4-chloro-2-methylaniline reaction was complete. 5 mL of water was added to the reaction solution, and the reaction was quenched by stirring for 20 min. The reaction solution was then extracted three times with 5 mL of dichloromethane each time. The organic phases were combined, dried over anhydrous sodium sulfate, and distilled under reduced pressure to obtain crude 2-amino-5-chloro-N,3-dimethylbenzamide. The crude product was recrystallized from 6 ml of 95% ethanol to obtain 1.827 g of 2-amino-5-chloro-N,3-dimethylbenzamide, with a yield of 92.29% and an HPLC purity of 97.8% (area normalized).

[0031] Example 6 1.41 g (10 mmol) of 4-chloro-2-methylaniline was weighed and added to 10 mL of dichloromethane. The reaction solution was cooled to 0 °C under nitrogen protection. Then, 0.58 g of methyl isocyanate (12 mmol) was added to the reaction solution, and the mixture was stirred for 15 min after the addition was complete. Next, 1.39 g of anhydrous aluminum trichloride (10.5 mmol) was slowly added to the reaction solution at 0 °C, and the mixture was kept at this temperature for 15 min after the addition was complete. The reaction solution was then heated to 25 °C and reacted for 16 h. HPLC analysis confirmed that the 4-chloro-2-methylaniline reaction was complete. 5 mL of water was added to the reaction solution, and the reaction was quenched by stirring for 20 min. The reaction solution was then extracted three times with 5 mL of dichloromethane each time. The organic phases were combined, dried over anhydrous sodium sulfate, and distilled under reduced pressure to obtain crude 2-amino-5-chloro-N,3-dimethylbenzamide. The crude product was recrystallized from 6 ml of 95% ethanol to obtain 1.848 g of 2-amino-5-chloro-N,3-dimethylbenzamide, with a yield of 93.31% and an HPLC purity of 98.2% (area normalized).

[0032] Example 7 1.41 g (10 mmol) of 4-chloro-2-methylaniline was weighed and added to 10 mL of dichloromethane. The reaction solution was cooled to 0 °C under nitrogen protection. Then, 0.58 g of methyl isocyanate (12 mmol) was added to the reaction solution, and the mixture was stirred for 15 min after the addition was complete. Next, 1.46 g of anhydrous aluminum trichloride (11 mmol) was slowly added to the reaction solution at 0 °C, and the mixture was kept at this temperature for 15 min after the addition was complete. The reaction solution was then heated to 25 °C and reacted for 13 h. HPLC analysis confirmed that the 4-chloro-2-methylaniline reaction was complete. 5 mL of water was added to the reaction solution, and the reaction was quenched by stirring for 20 min. The reaction solution was then extracted three times with 5 mL of dichloromethane each time. The organic phases were combined, dried over anhydrous sodium sulfate, and distilled under reduced pressure to obtain crude 2-amino-5-chloro-N,3-dimethylbenzamide. The crude product was recrystallized from 6 ml of 95% ethanol to obtain 1.877 g of 2-amino-5-chloro-N,3-dimethylbenzamide, with a yield of 94.82% and an HPLC purity of 98.2% (area normalized).

[0033] Example 8 1.41 g (10 mmol) of 4-chloro-2-methylaniline was weighed and added to 10 mL of dichloromethane. The reaction solution was cooled to 0 °C under nitrogen protection. Then, 0.58 g of methyl isocyanate (12 mmol) was added to the reaction solution, and the mixture was stirred for 15 min after the addition was complete. Then, 1.99 g of anhydrous aluminum trichloride (15 mmol) was slowly added to the reaction solution at 0 °C. After the addition was complete, the reaction was maintained at this temperature for 15 min, and then the reaction solution was heated to 25 °C and reacted for 9 h. HPLC analysis was performed to confirm that the 4-chloro-2-methylaniline reaction was complete. 5 mL of water was added to the reaction solution, and the reaction was quenched by stirring for 20 min. The reaction solution was then extracted three times with 5 mL of dichloromethane each time. The organic phases were combined, dried over anhydrous sodium sulfate, and distilled under reduced pressure to obtain crude 2-amino-5-chloro-N,3-dimethylbenzamide. The crude product was recrystallized from 6 ml of 95% ethanol to give 1.881 g of 2-amino-5-chloro-N,3-dimethylbenzamide, with a yield of 95.1% and an HPLC purity of 97.8% (area normalized).

[0034] Example 9 1.41 g (10 mmol) of 4-chloro-2-methylaniline was weighed and added to 10 mL of dichloromethane. The reaction solution was cooled to 0 °C under nitrogen protection. Then, 0.58 g of methyl isocyanate (12 mmol) was added to the reaction solution, and the mixture was stirred for 15 min after the addition was complete. Next, 2.66 g of anhydrous aluminum trichloride (20 mmol) was slowly added to the reaction solution at 0 °C, and the mixture was kept at this temperature for 15 min after the addition was complete. The reaction solution was then heated to 25 °C and reacted for 8 h. HPLC analysis confirmed that the 4-chloro-2-methylaniline reaction was complete. 5 mL of water was added to the reaction solution, and the reaction was quenched by stirring for 20 min. The reaction solution was then extracted three times with 5 mL of dichloromethane each time. The organic phases were combined, dried over anhydrous sodium sulfate, and distilled under reduced pressure to obtain crude 2-amino-5-chloro-N,3-dimethylbenzamide. The crude product was recrystallized from 6 ml of 95% ethanol to obtain 1.878 g of 2-amino-5-chloro-N,3-dimethylbenzamide, with a yield of 94.92% and an HPLC purity of 98.1% (area normalized).

[0035] Example 10 1.41 g (10 mmol) of 4-chloro-2-methylaniline was weighed and added to 10 mL of 1,2-dichloroethane. The reaction solution was cooled to 0 °C under nitrogen protection. Then, 0.58 g of methyl isocyanate (12 mmol) was added to the reaction solution, and the mixture was stirred for 15 min after the addition was complete. Next, 1.6 g of anhydrous aluminum trichloride (12 mmol) was slowly added to the reaction solution at 0 °C, and the mixture was kept at this temperature for 15 min after the addition was complete. The reaction solution was then heated to 25 °C and reacted for 8 h. HPLC analysis confirmed that the 4-chloro-2-methylaniline reaction was complete. 5 mL of water was added to the reaction solution, and the reaction was quenched by stirring for 20 min. The reaction solution was then extracted three times with 5 mL of 1,2-dichloroethane (3 times the volume of 1,2-dichloroethane). The organic phases were combined, dried over anhydrous sodium sulfate, and distilled under reduced pressure to obtain crude 2-amino-5-chloro-N,3-dimethylbenzamide. The crude product was recrystallized from 6 ml of 95% ethanol to give 1.872 g of 2-amino-5-chloro-N,3-dimethylbenzamide, with a yield of 94.66% and an HPLC purity of 99.5% (area normalized).

[0036] Example 11 1.41 g (10 mmol) of 4-chloro-2-methylaniline was weighed and added to 10 mL of anhydrous toluene. The reaction solution was cooled to 0 °C under nitrogen protection. Then, 0.58 g of methyl isocyanate (12 mmol) was added to the reaction solution, and the mixture was stirred for 15 min after the addition was complete. Next, 2.66 g of anhydrous aluminum trichloride (20 mmol) was slowly added to the reaction solution at 0 °C. After the addition was complete, the reaction solution was kept at this temperature for 15 min, and then heated to 25 °C and reacted for 10 h. HPLC analysis was performed to confirm that the 4-chloro-2-methylaniline reaction was complete. 5 mL of water was added to the reaction solution, and the reaction was quenched by stirring for 20 min. The reaction solution was then extracted three times with 5 mL of anhydrous toluene. The organic phases were combined, dried over anhydrous sodium sulfate, and distilled under reduced pressure to obtain crude 2-amino-5-chloro-N,3-dimethylbenzamide. The crude product was recrystallized from 6 ml of 95% ethanol to obtain 1.878 g of 2-amino-5-chloro-N,3-dimethylbenzamide, with a yield of 94.92% and an HPLC purity of 98.1% (area normalized).

[0037] Comparative Example 1 1.41 g (10 mmol) of 4-chloro-2-methylaniline was weighed and added to 10 mL of dichloromethane. The reaction solution was cooled to 0 °C under nitrogen protection. Then, 0.58 g of methyl isocyanate (12 mmol) was added to the reaction solution, and the mixture was stirred for 15 min after the addition was complete. Next, 3.34 g of tin tetrachloride (12 mmol) was slowly added to the reaction solution at 0 °C, and the mixture was kept at this temperature for 15 min after the addition was complete. The reaction solution was then heated to 25 °C and reacted for 25 h. HPLC analysis of a sample showed that the content of 2-amino-5-chloro-N,3-dimethylbenzamide in the reaction solution was only 1%, at which point the reaction was terminated. When tin tetrachloride was used as a catalyst, almost no product was formed.

[0038] Comparative Example 2 1.41 g (10 mmol) of 4-chloro-2-methylaniline was weighed and added to 10 mL of dichloromethane. The reaction solution was cooled to 0 °C under nitrogen protection. Then, 0.58 g of methyl isocyanate (12 mmol) was added to the reaction solution, and the mixture was stirred for 15 min after the addition was complete. Next, 2.28 g of titanium tetrachloride (12 mmol) was slowly added to the reaction solution at 0 °C, and the mixture was kept at this temperature for 15 min after the addition was complete. The reaction solution was then heated to 25 °C and reacted for 25 h. HPLC analysis of a sample showed that the content of 2-amino-5-chloro-N,3-dimethylbenzamide in the reaction solution was 11%, at which point the reaction was terminated. The efficiency of catalytic product preparation was also low when titanium tetrachloride was used as a catalyst.

[0039] Comparative Example 3 1.41 g (10 mmol) of 4-chloro-2-methylaniline was weighed and added to 10 mL of dichloromethane. The reaction solution was cooled to 0 °C under nitrogen protection. Then, 0.58 g of methyl isocyanate (12 mmol) was added to the reaction solution, and the mixture was stirred for 15 min after the addition was complete. Next, 2.80 g of zirconium tetrachloride (12 mmol) was slowly added to the reaction solution at 0 °C. After the addition was complete, the reaction was maintained at this temperature for 15 min, and then the reaction solution was heated to 25 °C and reacted for 25 h. HPLC analysis of the sample showed no formation of 2-amino-5-chloro-N,3-dimethylbenzamide, and the reaction was terminated.

[0040] Comparative Example 4 1.41 g (10 mmol) of 4-chloro-2-methylaniline was weighed and added to 10 mL of dichloromethane. The reaction solution was cooled to 0 °C under nitrogen protection, and then 0.58 g (12 mmol) of methyl isocyanate was added. After the addition was complete, the mixture was stirred for 15 min. The reaction solution was then heated to 25 °C and reacted for 10 h. HPLC analysis of a sample showed no formation of 2-amino-5-chloro-N,3-dimethylbenzamide. The reaction solution was then heated to reflux and reacted for 3 h. HPLC analysis of a sample again showed no formation of 2-amino-5-chloro-N,3-dimethylbenzamide.

[0041] Although the present invention has been described in detail by way of preferred embodiments, the present invention is not limited thereto. Various equivalent modifications or substitutions can be made to the embodiments of the present invention by those skilled in the art without departing from the spirit and essence of the invention, and such modifications or substitutions should all be within the scope of the present invention. Any variations or substitutions that can be easily conceived by those skilled in the art within the technical scope disclosed in the present invention should also be covered within the protection scope of the present invention.

Claims

1. A method for preparing 2-amino-5-chloro-N,3-dimethylbenzamide, characterized in that, 2-Amino-5-chloro-N,3-dimethylbenzamide was obtained by reacting 4-chloro-2-methylaniline with methyl isocyanate under the action of Lewis acid. The Lewis acid is one of ZnCl2, AlCl3, BCl3, or FeCl3.

2. The method for preparing 2-amino-5-chloro-N,3-dimethylbenzamide as described in claim 1, characterized in that, The Lewis acid is AlCl3.

3. The method for preparing 2-amino-5-chloro-N,3-dimethylbenzamide as described in claim 1, characterized in that, Includes the following steps: 4-Chloro-2-methylaniline was added to a solvent, and the reaction solution was cooled to -5℃ to 5℃ under nitrogen protection. Then, methyl isocyanate was added to the reaction solution, and Lewis acid was added to the reaction solution at -5℃ to 5℃. After the reaction was maintained at this temperature for 15 min, the temperature was raised to 10℃ to 40℃. After the reaction was completed, water was added to quench the reaction solution, and the solution was extracted with dichloromethane. The organic phase was washed with water, dried, and the solvent was removed to obtain 2-amino-5-chloro-N,3-dimethylbenzamide.

4. The method for preparing 2-amino-5-chloro-N,3-dimethylbenzamide as described in claim 3, characterized in that, The molar ratio of 4-chloro-2-methylaniline to Lewis acid is 1:1 to 3.

5. The method for preparing 2-amino-5-chloro-N,3-dimethylbenzamide as described in claim 3 or 4, characterized in that, The molar ratio of 4-chloro-2-methylaniline to Lewis acid is 1:1.

2.

6. The method for preparing 2-amino-5-chloro-N,3-dimethylbenzamide as described in claim 3, characterized in that, The molar ratio of 4-chloro-2-methylaniline to methyl isocyanate is 1:1~2.

7. The method for preparing 2-amino-5-chloro-N,3-dimethylbenzamide as described in claim 3 or 6, characterized in that, The molar ratio of 4-chloro-2-methylaniline to methyl isocyanate is 1:1.

02.

8. The method for preparing 2-amino-5-chloro-N,3-dimethylbenzamide as described in claim 1 or 3, characterized in that, It also includes a process for refining 2-amino-5-chloro-N,3-dimethylbenzamide, wherein recrystallization is performed using 95% ethanol.

9. The method for preparing 2-amino-5-chloro-N,3-dimethylbenzamide as described in claim 3, characterized in that, The solvent is dichloromethane, 1,2-dichloroethane, chloroform, benzene, or toluene.

10. The method for preparing 2-amino-5-chloro-N,3-dimethylbenzamide as described in claim 3, characterized in that, The solvent is dichloromethane.