Synthesis method of 2-amino-5-chloro-N, 3-dimethyl benzamide

Abstract

The invention relates to a synthesis method of 2-amino-5-chloro-N, 3-dimethyl benzamide, which comprises the following steps: hydrogenation reaction: adding 3-methyl-2-nitrobenzoic acid, palladium on carbon, methanol, nitrogen and hydrogen for replacement; filtering to remove palladium and carbon, adding activated carbon into filtrate for decoloration, concentrating under reduced pressure, crystallizing, filtering and drying; cyclization reaction: adding 3-methyl-2-nitrobenzoic acid, dichloromethane, oxalyl chloride and aluminum trichloride, reacting, separating liquid, removing a water phase, concentrating an organic phase under reduced pressure, cooling, crystallizing, filtering and drying to obtain 2-amino-5-chloro-N, 3-dimethylbenzamide; 2-amino-5-chloro-N, 3-dimethylbenzamide, ethanol, a catalyst PIDA and CuCl2 are sequentially added, nitrogen displacement and stirring heating are carried out, a reaction is carried out for 12 h, a 10% sodium bicarbonate aqueous solution is dropwise added until the pH value is 6.0-6.5, the temperature is reduced to the room temperature, and filtering and drying are carried out; and ring-opening reaction: adding 6-chloro-3-methyl itaconic anhydride and purified water, replacing with nitrogen, cooling, adding 40% methylamine aqueous solution, heating, sampling, detecting reaction, cooling, crystallizing, filtering and drying.

Description

Technical Field

[0001] This invention relates to a method for synthesizing 2-amino-5-chloro-N,3-dimethylbenzamide. Background Technology

[0002] 2-Amino-5-chloro-N,3-dimethylbenzamide, also known as K-amine, is a key intermediate in the production of chlorantraniliprole, which has the chemical formula C1. 18 H 14 BrC l2 N5O2, CAS: 500008-45-7, is an o-aminobenzamide insecticide developed by DuPont in 2007. It appears as a white crystalline powder. Chlorantraniliprole is a new type of highly effective broad-spectrum insecticide that has significant control effects on a variety of pests.

[0003] Currently, there are many publicly available literature reports on the process of 2-amino-5-chloro-N,3-dimethylbenzamide: 1. Patent publication number WO2006062978 discloses a method that uses methyl 3-methyl-2-nitro-benzoate as a starting material and then proceeds through catalytic hydrogenation, chlorination, and amino ester exchange to obtain 2-amino-5-chloro-N,3-dimethylbenzamide with a total yield of 75% in three steps. However, this method requires the use of dry ice for cooling, which places high demands on the production equipment. 2. Patent publication number CN116987002A discloses a method for obtaining 2-amino-5-chloro-N,3-dimethylbenzamide by using o-methylaniline as a raw material through acetylation, chlorination, oxime, cyclization, oxidation, and aminolysis. This route involves many reaction steps, has a low overall yield, and is cumbersome to operate. 3. Patent publication number CN111517975A discloses that 2-amino-5-chloro-N,3-dimethylbenzamide is obtained by hydrogenation, chlorination, esterification and amino ester exchange of methyl 3-methyl-2-nitro-benzoate as raw material, with a total yield of 80%. However, this route uses chlorine as chlorination reagent, which requires high equipment and process control. 4. Patent publication number CN1115583895A discloses a process using 3-methyl-5-chlorobenzoic acid as a raw material, which involves nitration, acylation, amination, and hydrogenation to obtain 2-amino-5-chloro-N,3-dimethylbenzamide with a total yield of 80%. However, the traditional nitration process carries significant risks. Summary of the Invention

[0004] The present invention addresses the problems existing in the prior art by providing a method for synthesizing 2-amino-5-chloro-N,3-dimethylbenzamide that not only has a high overall yield and is safe and controllable, but is also environmentally friendly.

[0005] To achieve the above objectives, the technical solution adopted by the present invention is: a method for synthesizing 2-amino-5-chloro-N,3-dimethylbenzamide, comprising the following steps: Step 1: Hydrogenation reaction: Add 3-methyl-2-nitrobenzoic acid, palladium on carbon, and methanol to the hydrogenation reactor. Purify with nitrogen three times and with hydrogen three times. The reaction temperature is 25-80℃ and the reaction time is 0.5-4h. After the reaction is complete, filter to remove palladium on carbon. Add activated carbon to the filtrate for decolorization, concentrate under reduced pressure, crystallize, filter, and dry to obtain 3-methyl-2-aminobenzoic acid. Second step cyclization reaction: 3-Methyl-2-nitrobenzoic acid, dichloromethane, oxalyl chloride, and aluminum trichloride were added to a sealed reactor and reacted at 0-20℃ for 4 hours. Water was added and stirred for 30 minutes. The aqueous phase was discarded by separation, and the organic phase was concentrated under reduced pressure to 2 volumes. The mixture was cooled to 0-5℃ to crystallize for 2 hours, filtered, and dried to obtain 2-amino-5-chloro-N,3-dimethylbenzamide. Third step: Chlorination reaction: 2-Amino-5-chloro-N, 3-dimethylbenzamide, ethanol, catalyst PIDA, and CuCl2 were added sequentially to a sealed reactor. After nitrogen purging three times, the mixture was stirred and heated to 40°C. The reaction was carried out for 12 hours. A 10% sodium bicarbonate aqueous solution was added dropwise to adjust the pH to 6.0-6.5. The mixture was then cooled to room temperature, filtered, and dried to obtain 6-chloro-3-methylitanic anhydride. Step 4: Ring-opening reaction: 6-Chloro-3-methylitoric anhydride and purified water were added to a sealed reactor. The reactor was purged with nitrogen three times and cooled to 0-5℃. A 40% methylamine aqueous solution was added, and the reactor was heated to 20-30℃ for 8 hours. After the reaction was completed, the reactor was cooled to 0-10℃ for 2 hours to allow crystals to precipitate. The crystals were then filtered and dried to obtain 2-amino-5-chloro-N,3-dimethylbenzamide.

[0006] Furthermore, in the first step of the hydrogenation reaction, the amount of 3-methyl-2-aminobenzoic acid added is 3 kg; the amount of palladium on carbon added is 0.5%-5% wt; the amount of methanol added is 3-8 wt; and the amount of activated carbon added to the filtrate is 0.01-0.05 wt.

[0007] Furthermore, in the first step of the hydrogenation reaction, 2.43 kg of 3-methyl-2-aminobenzoic acid was obtained with a purity of 99.1% and a yield of 97%.

[0008] Furthermore, in the second cyclization reaction, the amount of 3-methyl-2-aminobenzoic acid added is 2 kg; the amount of dichloromethane added is 4-8 wt; the amount of oxaloyl chloride added is 0.8-1.0 wt; the amount of aluminum trichloride added is 0.05-0.10 wt; and the amount of water added is 2 kg.

[0009] Furthermore, in the second cyclization reaction, 2.27 kg of 2-amino-5-chloro-N,3-dimethylbenzamide, a white solid, was obtained by drying, with a yield of 97% and a purity greater than 99%.

[0010] Furthermore, in the third step of the chlorination reaction, the amount of 3-methylitanic anhydride added is 2 kg, the amount of ethanol added is 3-6 wt, the amount of catalyst PIDA added is 0.05-0.10 wt, and the amount of CuCl2 added is 0.4-0.8 wt.

[0011] Furthermore, in the third step of the chlorination reaction, filtration and drying yielded 2.33 kg of 6-chloro-3-methylitoric anhydride, a white solid with a yield of 98% and a purity greater than 97%.

[0012] Furthermore, in the fourth ring-opening reaction, the amount of 6-chloro-3-methylitoric anhydride added is 2 kg, the amount of pure water added is 3-5 wt, and the amount of 40% methylamine aqueous solution added is 0.3-0.5 wt.

[0013] Furthermore, in the fourth ring-opening reaction, filtration and drying yielded 1.78 kg of 2-amino-5-chloro-N,3-dimethylbenzamide as a white solid, with a yield of 95% and a purity greater than 99.5%.

[0014] Compared with the prior art, the present invention has the following advantages: the present invention is simple to operate, has low requirements for equipment, produces less waste, only generates wastewater in one step, causes less environmental pollution, and the final product is not a white solid, which is of good quality compared with gray solid products on the market. Attached Figure Description

[0015] Figure 1 This is the reaction formula of the present invention. Detailed Implementation

[0016] The present invention will now be described in further detail with reference to the accompanying drawings and specific embodiments.

[0017] In the description of this invention, it should be understood that the terms "longitudinal", "lateral", "up", "down", "front", "rear", "left", "right", "vertical", "horizontal", "top", "bottom", "inner", "outer", etc., indicate the orientation or positional relationship based on the orientation or positional relationship shown in the accompanying drawings, and are only for the convenience of describing this invention, and are not intended to indicate or imply that the device or element referred to must have a specific orientation, or be constructed and operated in a specific orientation, and therefore should not be construed as a limitation of this invention.

[0018] like Figure 1As shown, this invention provides a method for synthesizing 2-amino-5-chloro-N,3-dimethylbenzamide, with the following reaction formula: in: Formula I: 3-Methyl-2-nitrobenzoic acid; Formula II: 3-Methyl-2-aminobenzoic acid; Formula III: 3-Methylitanic anhydride; Formula IV: 6-Chloro-3-methylitoric anhydride; Formula V: 2-amino-5-chloro-N,3-dimethylbenzamide.

[0019] The synthesis method includes the following steps: Step 1: Hydrogenation reaction: Add Formula I: 3-methyl-2-nitrobenzoic acid (3 kg), palladium on carbon (0.5%-5%wt, with Formula I as 1wt), and methanol (3-8wt) to the hydrogenation reactor. Purify with nitrogen 3 times and hydrogen 3 times. The reaction temperature is 25-80℃, and the reaction time is 0.5-4h. After the reaction is complete, filter to remove palladium on carbon. Add activated carbon (0.01-0.05wt) to the filtrate for decolorization, concentrate under reduced pressure, crystallize, filter, and dry to obtain 2.43 kg of 3-methyl-2-aminobenzoic acid with a purity of 99.1% and a yield of 97%.

[0020] Second step cyclization reaction: 2 kg of Formula II (3-methyl-2-aminobenzoic acid), 4-8 wt of dichloromethane, 0.8-1.0 wt of oxaloyl chloride, and 0.05-0.10 wt of aluminum trichloride were added to a sealed reactor and reacted at 0-20℃ for 4 h. After the reaction was completed, 2 kg of water was added and stirred for 30 min. The aqueous phase was discarded, and the organic phase was concentrated under reduced pressure to 2 volumes. The mixture was then cooled to 0-5℃ to crystallize for 2 h. After filtration and drying, 2.27 kg of 2-amino-5-chloro-N,3-dimethylbenzamide was obtained as a white solid with a yield of 97% and a purity greater than 99%.

[0021] Third step: Chlorination reaction: Add 2 kg of Formula III (3-methylitanic anhydride), 3-6 wt of ethanol (with Formula III as 1 wt), 0.05-0.10 wt of catalyst PIDA, and 0.4-0.8 wt of CuCl2 sequentially to a sealed reactor. After purging with nitrogen three times, stir and heat to 40°C, react for 12 hours, and take a sample to check if the reaction is complete. Add 10% sodium bicarbonate aqueous solution dropwise to adjust the pH to 6.0-6.5, cool to room temperature, filter and dry to obtain 2.33 kg of 6-chloro-3-methylitanic anhydride, a white solid with a yield of 98% and a purity greater than 97%.

[0022] Step 4: Ring-opening reaction: Add 2 kg of Formula IV (6-chloro-3-methylitoric anhydride) and 3-5 wt of purified water to a sealed reactor. Purge with nitrogen three times, cool to 0-5℃, add 0.3-0.5 wt of 40% methylamine aqueous solution, heat to 20-30℃ and react for 8 h. Take a sample to check if the reaction is complete, cool to 0-10℃ to crystallize for 2 h, filter and dry to obtain 1.78 kg of 2-amino-5-chloro-N,3-dimethylbenzamide, a white solid with a yield of 95% and a purity greater than 99.5%.

[0023] Example 1-1 Formula I 3 kg, palladium on carbon 150 g, and methanol 9 kg were added sequentially to a hydrogenation reactor. The reactor was purged with nitrogen three times and hydrogen three times. The reaction temperature was 30-40℃, and the reaction was carried out for 1 h. After the reaction was completed, the palladium on carbon was removed by filtration. The mixture was concentrated under reduced pressure to 3 volumes, crystallized at 5-10℃, filtered, and dried under vacuum at 40-45℃ to obtain 2.43 kg of 3-methyl-2-aminobenzoic acid with a purity of 99.4% and a yield of 97%.

[0024] Examples 1-2 Add 2 kg of Formula II, 8 kg of dichloromethane, and 0.1 kg of aluminum trichloride to a sealed reactor. Purge the reactor three times with nitrogen and cool to 0-5°C. Slowly add 1.6 kg of oxalyl chloride. After the addition is complete, react at 0-5°C for 4 hours. Take a sample to check if the reaction is complete. Add 2 kg of water and stir for 30 minutes. Separate the liquid and discard the aqueous phase. Concentrate the organic phase under reduced pressure to 2 volumes. Cool to 0-5°C to crystallize for 2 hours. Filter and dry under vacuum at 40-45°C to obtain 2.27 kg of 2-amino-5-chloro-N,3-dimethylbenzamide, a white solid with a yield of 97% and a purity of 99.1%.

[0025] Examples 1-3 Add 2 kg of Formula III, 6 kg of ethanol, 0.1 kg of catalyst PIDA, and 0.8 kg of CuCl2 sequentially to a sealed reactor. After purging with nitrogen three times, stir and heat to 40°C, react for 12 hours, and take a sample to check if the reaction is complete. Add 10% sodium bicarbonate aqueous solution dropwise to adjust the pH to 6.0-6.5, cool to room temperature, filter, and vacuum dry at 40-45°C to obtain 2.33 kg of 6-chloro-3-methylitanic anhydride, a white solid with a yield of 98% and a purity of 97.6%.

[0026] Examples 1-4 Add 2 kg of Formula IV and 6 kg of purified water to a sealed reactor. Purge the mixture with nitrogen three times and cool it to 0-5℃. Add 0.6 kg of 40% methylamine aqueous solution and heat to 20-25℃ for 8 hours. After the reaction is complete, cool to 0-5℃ to allow crystals to precipitate for 2 hours. Filter the solution and dry it under vacuum at 40-45℃ to obtain 1.78 kg of 2-amino-5-chloro-N,3-dimethylbenzamide, a white solid with a yield of 95% and a purity of 99.6%.

[0027] Example 2-1 Add 3 kg of Formula I, 100 g of palladium on carbon, and 15 kg of methanol sequentially to a hydrogenation reactor. Purify the reactor three times with nitrogen and three times with hydrogen. React at 30-40℃ for 3 hours. After the reaction is complete, filter to remove the palladium on carbon, concentrate under reduced pressure to 3 volumes, crystallize at 5-10℃, filter, and vacuum dry at 40-45℃ to obtain 2.45 kg of 3-methyl-2-aminobenzoic acid with a purity of 99.3% and a yield of 98%.

[0028] Example 2-2 Add 2 kg of Formula II, 12 kg of dichloromethane, and 0.16 kg of aluminum trichloride to a sealed reactor. Purge the reactor three times with nitrogen and cool to 0-5°C. Slowly add 1.8 kg of oxalyl chloride. After the addition is complete, react at 0-5°C for 4 hours. Take a sample to check if the reaction is complete. Add 2 kg of water and stir for 30 minutes. Separate the liquid and discard the aqueous phase. Concentrate the organic phase under reduced pressure to 2 volumes. Cool to 0-5°C to crystallize for 2 hours. Filter and dry under vacuum at 40-45°C to obtain 2.22 kg of 2-amino-5-chloro-N,3-dimethylbenzamide, a white solid with a yield of 95% and a purity of 99.1%.

[0029] Example 2-3 Add 2 kg of Formula III, 8 kg of ethanol, 0.14 kg of catalyst PIDA, and 1.2 kg of CuCl2 sequentially to a sealed reactor. After purging with nitrogen three times, stir and heat to 40°C, react for 12 hours, and take a sample to check if the reaction is complete. Add 10% sodium bicarbonate aqueous solution dropwise to adjust the pH to 6.0-6.5, cool to room temperature, filter, and vacuum dry at 40-45°C to obtain 2.27 kg of 6-chloro-3-methylitanic anhydride, a white solid with a yield of 98% and a purity of 97.9%.

[0030] Examples 2-4 Add 2 kg of Formula IV and 8 kg of purified water to a sealed reactor. Purge the mixture with nitrogen three times and cool it to 0-5°C. Add 0.8 kg of 40% methylamine aqueous solution and heat to 20-25°C. React for 8 hours. After the reaction is complete, cool to 0-5°C to allow crystals to precipitate for 2 hours. Filter the solution and dry it under vacuum at 40-45°C to obtain 1.81 kg of 2-amino-5-chloro-N,3-dimethylbenzamide, a white solid with a yield of 97% and a purity of 99.6%.

[0031] Example 3-1 Formula I 3 kg, palladium on carbon 15 g, and methanol 24 kg were added sequentially to a hydrogenation reactor. The reactor was purged with nitrogen three times and hydrogen three times. The reaction temperature was 30-40℃, and the reaction was carried out for 5 h. After the reaction was completed, the palladium on carbon was removed by filtration. The mixture was concentrated under reduced pressure to 3 volumes, crystallized at 5-10℃, filtered, and dried under vacuum at 40-45℃ to obtain 2.47 kg of 3-methyl-2-aminobenzoic acid with a purity of 99.5% and a yield of 99%.

[0032] Example 3-2 Add 2 kg of Formula II, 16 kg of dichloromethane, and 0.2 kg of aluminum trichloride to a sealed reactor. Purge the reactor three times with nitrogen and cool to 0-5°C. Slowly add 1.8 kg of oxalyl chloride. After the addition is complete, react at 0-5°C for 4 hours. Take a sample to check if the reaction is complete. Add 2 kg of water and stir for 30 minutes. Separate the liquid and discard the aqueous phase. Concentrate the organic phase under reduced pressure to 2 volumes. Cool to 0-5°C to crystallize for 2 hours. Filter and dry under vacuum at 40-45°C to obtain 2.24 kg of 2-amino-5-chloro-N,3-dimethylbenzamide, a white solid with a yield of 95% and a purity of 99.3%.

[0033] Example 3-3 Add 2 kg of Formula III, 12 kg of ethanol, 0.20 kg of catalyst PIDA, and 1.6 kg of CuCl2 sequentially to a sealed reactor. After purging with nitrogen three times, stir and heat to 40°C, react for 12 hours, and take a sample to check if the reaction is complete. Add 10% sodium bicarbonate aqueous solution dropwise to adjust the pH to 6.0-6.5, cool to room temperature, filter, and vacuum dry at 40-45°C to obtain 2.20 kg of 6-chloro-3-methylitoric anhydride, a white solid with a yield of 98% and a purity of 98.3%.

[0034] Examples 3-4 Add 2 kg of Formula IV and 10 kg of purified water to a sealed reactor. Purge the mixture with nitrogen three times and cool it to 0-5°C. Add 1.0 kg of 40% methylamine aqueous solution and heat to 20-25°C for 8 hours. After the reaction is complete, cool to 0-5°C to allow crystals to precipitate for 2 hours. Filter the solution and dry it under vacuum at 40-45°C to obtain 1.76 kg of 2-amino-5-chloro-N,3-dimethylbenzamide, a white solid with a yield of 94% and a purity of 99.8%.

[0035] The key chlorination step of this invention uses iodobenzene diacetate (PIDA), achieving a conversion rate of over 95%, which is significantly higher than existing reported routes and is suitable for industrial production.

[0036] The advantages of this invention are as follows: This invention provides a high-yield, safe, controllable, and environmentally friendly synthetic route for preparing the key intermediate 2-amino-5-chloro-N,3-dimethylbenzamide compound, which is essential for chlorantraniliprole. The synthetic method of this invention is simple to operate, requires minimal equipment, generates little waste, and is environmentally friendly. The final product is a white solid, which has a superior appearance compared to gray solid products on the market, demonstrating significant advantages over existing processes.

[0037] If this invention discloses or relates to components or structural parts that are fixedly connected to each other, then, unless otherwise stated, a fixed connection can be understood as: a fixed connection that can be detached (e.g., using bolts or screws), or a fixed connection that cannot be detached (e.g., riveting, welding). Of course, a fixed connection can also be replaced by an integral structure (e.g., manufactured in one piece using a casting process) (except where it is obviously impossible to use an integral molding process).

[0038] In addition, unless otherwise stated, the terms used in any of the technical solutions disclosed in this invention to indicate positional relationships or shapes include states or shapes that are similar to, close to, or approximate with those states or shapes.

[0039] Any component provided by this invention can be assembled from multiple individual components or can be a single component manufactured by a one-piece molding process.

[0040] Finally, it should be noted that the above embodiments are only used to illustrate the technical solutions of the present invention and not to limit them; although the present invention has been described in detail with reference to preferred embodiments, those skilled in the art should understand that modifications can still be made to the specific implementation of the present invention or equivalent substitutions can be made to some technical features without departing from the spirit of the technical solutions of the present invention, and all such modifications and substitutions should be covered within the scope of the technical solutions claimed in the present invention.

Claims

1. A method for synthesizing 2-amino-5-chloro-N,3-dimethylbenzamide, characterized in that: Includes the following steps: Step 1: Hydrogenation reaction: Add 3-methyl-2-nitrobenzoic acid, palladium on carbon, and methanol to the hydrogenation reactor. Purify with nitrogen three times and with hydrogen three times. The reaction temperature is 25-80℃ and the reaction time is 0.5-4h. After the reaction is complete, filter to remove palladium on carbon. Add activated carbon to the filtrate for decolorization, concentrate under reduced pressure, crystallize, filter, and dry to obtain 3-methyl-2-aminobenzoic acid. Second step cyclization reaction: 3-Methyl-2-nitrobenzoic acid, dichloromethane, oxalyl chloride, and aluminum trichloride were added to a sealed reactor and reacted at 0-20℃ for 4 hours. Water was added and stirred for 30 minutes. The aqueous phase was discarded by separation, and the organic phase was concentrated under reduced pressure to 2 volumes. The mixture was cooled to 0-5℃ to crystallize for 2 hours, filtered, and dried to obtain 2-amino-5-chloro-N,3-dimethylbenzamide. Third step: Chlorination reaction: 2-Amino-5-chloro-N, 3-dimethylbenzamide, ethanol, catalyst PIDA, and CuCl2 were added sequentially to a sealed reactor. After purging with nitrogen three times, the mixture was stirred and heated to 40°C. The reaction was carried out for 12 hours. A 10% sodium bicarbonate aqueous solution was added dropwise to adjust the pH to 6.0-6.

5. The mixture was then cooled to room temperature, filtered, and dried to obtain 6-chloro-3-methylitanic anhydride. Step 4: Ring-opening reaction: 6-Chloro-3-methylitoric anhydride and purified water were added to a sealed reactor. The reactor was purged with nitrogen three times and cooled to 0-5℃. A 40% methylamine aqueous solution was added, and the reactor was heated to 20-30℃ for 8 hours. After the reaction was completed, the reactor was cooled to 0-10℃ for 2 hours to allow crystals to precipitate. The crystals were then filtered and dried to obtain 2-amino-5-chloro-N,3-dimethylbenzamide.

2. The method for synthesizing 2-amino-5-chloro-N,3-dimethylbenzamide according to claim 1, characterized in that: In the first step of the hydrogenation reaction, 3 kg of 3-methyl-2-aminobenzoic acid was added; 0.5%-5%wt of palladium on carbon was added; 3-8wt of methanol was added; and 0.01-0.05wt of activated carbon was added to the filtrate.

3. The method for synthesizing 2-amino-5-chloro-N,3-dimethylbenzamide according to claim 2, characterized in that: In the first step of the hydrogenation reaction, 2.43 kg of 3-methyl-2-aminobenzoic acid was obtained with a purity of 99.1% and a yield of 97%.

4. The method for synthesizing 2-amino-5-chloro-N,3-dimethylbenzamide according to claim 1, characterized in that: In the second cyclization reaction, 2 kg of 3-methyl-2-aminobenzoic acid was added; 4-8 wt of dichloromethane was added; 0.8-1.0 wt of oxaloyl chloride was added; 0.05-0.10 wt of aluminum trichloride was added; and 2 kg of water was added.

5. The method for synthesizing 2-amino-5-chloro-N,3-dimethylbenzamide according to claim 4, characterized in that: In the second cyclization reaction, 2.27 kg of 2-amino-5-chloro-N,3-dimethylbenzamide, a white solid, was obtained by drying, with a yield of 97% and a purity greater than 99%.

6. The method for synthesizing 2-amino-5-chloro-N,3-dimethylbenzamide according to claim 1, characterized in that: In the third step of the chlorination reaction, the amount of 3-methylitanic anhydride added is 2 kg, the amount of ethanol added is 3-6 wt, the amount of catalyst PIDA added is 0.05-0.10 wt, and the amount of CuCl2 added is 0.4-0.8 wt.

7. The method for synthesizing 2-amino-5-chloro-N,3-dimethylbenzamide according to claim 6, characterized in that: In the third step of the chlorination reaction, filtration and drying yielded 2.33 kg of 6-chloro-3-methylitoric anhydride, a white solid with a yield of 98% and a purity greater than 97%.

8. The method for synthesizing 2-amino-5-chloro-N,3-dimethylbenzamide according to claim 1, characterized in that: In the fourth ring-opening reaction, the amount of 6-chloro-3-methylitoric anhydride added is 2 kg, the amount of pure water added is 3-5 wt, and the amount of 40% methylamine aqueous solution added is 0.3-0.5 wt.

9. The method for synthesizing 2-amino-5-chloro-N,3-dimethylbenzamide according to claim 8, characterized in that: In the fourth ring-opening reaction, filtration and drying yielded 1.78 kg of 2-amino-5-chloro-N,3-dimethylbenzamide, a white solid with a yield of 95% and a purity greater than 99.5%.

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