Process for the synthesis of 2-chloro-4-methanesulfonylbenzoic acid

Abstract

The application belongs to the chemical industry field, and particularly relates to a 2-chloro-4-methylsulfonylbenzoic acid synthesis method, and a reaction equation is as follows: The application has the beneficial effects that a chlorination step is cancelled, production steps are reduced, production equipment and process operation are simplified, loss caused by material transfer is reduced, and product yield is improved.

Description

Technical Field

[0001] This invention relates to the field of chemical engineering, specifically a method for synthesizing 2-chloro-4-methanesulfonylbenzoic acid. Background Technology

[0002] 2-Chloro-4-methanesulfonylbenzoic acid (CMSBA) is a key intermediate in the synthesis of the novel herbicide 3-(2-chloro-4-(methanesulfonyl)benzoyl)bicyclo(3.2.1)octane-2,4-dione (trade name: bicyclosulfonyl benzoate), and there is a large demand for it both domestically and internationally.

[0003] The reported process mainly uses 4-methylbenzylthiophenol as the starting material, and obtains the product through four steps of reaction and recrystallization purification, with an overall yield of 57%. This process uses 4-methylbenzylthiophenol obtained by reducing 4-methylbenzenesulfonyl chloride as the starting material, which is expensive. Furthermore, the subsequent reaction steps re-oxidize it to sulfonyl groups. The reaction process involves expensive redox reagents, a relatively unclean redox process, and large fluctuations in sulfur valence state. Therefore, this process has poor redox economics, produces many by-products, has low product yield, and generates a large amount of wastewater.

[0004] Another method involves first synthesizing 4-methylbenzenesulfonyl chloride from toluene and chlorosulfonic acid, then successively reducing it to sodium 4-methylbenzenesulfinate, methylating it to 4-methanesulfonyltoluene, chlorinating it to 2-chloro-4-methanesulfonyltoluene, and finally oxidizing the methyl group to obtain CMSBA. After separation and recrystallization, the pure product is obtained, with an overall yield of 68.8%. This route has certain industrial value and is currently the primary industrial process. However, this route is lengthy, especially in the chlorination process which generates a large amount of high-content waste sulfuric acid, making treatment difficult and resulting in high waste costs. Therefore, developing an economical, environmentally friendly, and efficient new process for CMSBA production is of significant theoretical and practical importance. Summary of the Invention

[0005] To address the problems mentioned in the background section, this invention provides a method for synthesizing 2-chloro-4-methanesulfonylbenzoic acid.

[0006] To achieve the above objectives, the present invention provides the following technical solution: a method for synthesizing 2-chloro-4-methanesulfonylbenzoic acid, the reaction equation of which is as follows:

[0007]

[0008] The synthesis method includes the following steps;

[0009] S1: Add chlorosulfonic acid to the reaction vessel, start the stirrer at 300-400 rpm, slowly add ammonium chloride, and after the ammonium chloride is added, slowly add o-chlorotoluene dropwise into the bottle, control the temperature inside the bottle at 55-60℃, and add o-chlorotoluene dropwise for 1.5-2.5 hours. After the dropwise addition is complete, keep the system at this temperature for 2 hours to complete the reaction.

[0010] S2: Add tap water to another reaction flask in advance and cool it to 0-5℃. Slowly add the product from S1 dropwise to the flask, controlling the temperature at 10-20℃. Hydrolyze and destroy the excess chlorosulfonic acid. The system releases a lot of heat. After the dropwise addition is complete, the heat release ends. Stop stirring after 1 hour.

[0011] S3: After hydrolyzing and destroying chlorosulfonic acid, dichloromethane solvent is added for extraction. A small amount of water is added to the mixture for washing and filtration. The crystals after filtration are the product 3-chloro-4-methylbenzenesulfonyl chloride. The mother liquor is filtered and allowed to stand to separate into layers. The upper layer is an oil layer, the middle layer is an acidic water layer, and the lower layer is the by-product 2-methyl-3-chlorobenzenesulfonyl chloride.

[0012] S4: Add water to a new reaction flask, heat to 45°C, turn on the stirrer at 300-400 rpm, add sodium sulfite and sodium carbonate, heat to 70°C, slowly add 3-chloro-4-methylbenzenesulfonyl chloride in batches, maintain the temperature at 76-78°C during the addition process, and keep at this temperature for one hour after the addition is complete.

[0013] S5: After heat preservation, filter while hot, and transfer the mother liquor into a high-pressure reactor. Replace the air in the reactor three times with nitrogen, and then replace the nitrogen in the reactor three times with chloromethane. Start purging chloromethane and adjust the pressure. When the gas stops being introduced and the pressure in the reactor stops decreasing, keep it at the heat for 30 minutes. Confirm that the pressure in the reactor remains unchanged, then the reaction is complete. Transfer the material to a flask and adjust the pH to 9 with 30% liquid alkali. After adjusting the pH, start cooling with cooling water and stir until crystals precipitate. At about 45°C, filter and wash the material. Dry the washed material to obtain 2-chloro-4-methanesulfonyltoluene.

[0014] S6: 2-Chloro-4-methanesulfonyltoluene is further oxidized with nitric acid to obtain the product 2-chloro-4-methanesulfonylbenzoic acid.

[0015] Preferably, the mass ratio of chlorosulfonic acid, ammonium chloride and o-chlorotoluene in S1 is 0.8-1:0.02-0.03:1.

[0016] Preferably, the ratio of process water to chlorosulfonic acid used in S2 is 1:1.

[0017] Preferably, the solvent used in S3 is one of dichloromethane, dichloroethane, chloroform, toluene, and ethyl acetate.

[0018] Preferably, dichloromethane is used as the extraction solvent in step S3.

[0019] Preferably, the mass ratio of water, sodium sulfite, sodium carbonate, and 3-chloro-4-methylbenzenesulfonyl chloride in S4 is 2.25–2.30: 0.62–0.72: 0.51–0.58: 1.

[0020] Preferably, the pressure adjustment range in S5 is 0.5 to 0.55 MPa.

[0021] The beneficial effects of this invention are that it eliminates the chlorination step, reduces production steps, simplifies production equipment and process operations, reduces losses caused by material transfer, and improves product yield. Attached Figure Description

[0022] Figure 1 The image shows the HPLC chromatogram of 2-chloro-4-methanesulfonyltoluene.

[0023] Figure 2 This is a liquid chromatographic image of 2-chloro-4-methanesulfonylbenzoic acid. Detailed Implementation

[0024] Preferred embodiments of the present invention will now be described with reference to the accompanying drawings. Those skilled in the art should understand that these embodiments are merely illustrative of the technical principles of the present invention and are not intended to limit the scope of protection of the present invention.

[0025] Example 1:

[0026] S1: Add 50g of chlorosulfonic acid to a 500ml four-necked flask using a constant dropping method. Turn on the stirrer at 350rpm and add 1.5g of ammonium chloride. After the ammonium chloride is added, slowly add 55g of o-chlorotoluene dropwise into the flask, controlling the temperature inside the flask at 58℃. The o-chlorotoluene is added over 2 hours. After the addition is complete, maintain the system at this temperature for 2 hours, then take a sample for monitoring. The reaction is then complete.

[0027] S2: Add 50g of tap water to another 500ml four-necked flask and cool it to 5℃. Slowly add the product from S1 dropwise to the flask, controlling the temperature at 15℃, to hydrolyze and destroy the excess chlorosulfonic acid. The system releases a large amount of heat. After the addition is complete, the heat release ends. Stir for 1 hour and then stop.

[0028] S3: After hydrolyzing and destroying chlorosulfonic acid, 80g of dichloromethane was added for extraction. The mixture was allowed to stand and separate into layers. The lower organic phase was concentrated under reduced pressure, cooled to <10℃, and stirred for 1 hour. After washing with water and filtration, white crystals were obtained as the product 3-chloro-4-methylbenzenesulfonyl chloride. The mother liquor was concentrated and the above operation was repeated to obtain a secondary product, which could be mixed and used. Finally, the mother liquor was concentrated to remove the solvent, yielding the oil phase byproduct 2-methyl-3-chlorobenzenesulfonyl chloride.

[0029] S4: Add 80g of tap water to another 500ml four-necked flask, start stirring at 350rpm, heat to 45℃, add 21g of sodium sulfite and 18g of sodium carbonate, heat to 70℃, slowly add 35g of 3-chloro-4-methylbenzenesulfonyl chloride in batches, maintain the temperature at 77℃ during the addition process, and keep at this temperature for one hour after the addition is complete; take a sample for control, and the reaction is complete.

[0030] S5: After the reaction is complete, the reaction solution is filtered while hot, and the mother liquor is directly transferred to a 1L high-pressure reactor. After purging with nitrogen, it is then purged with chloromethane. Chloromethane is introduced and the pressure is adjusted. When the gas supply stops and the pressure inside the reactor stops decreasing, the reactor is kept at this temperature for 30 minutes. The reaction is considered complete when the pressure inside the reactor remains constant. The material is then transferred to a 1L four-necked flask. The pH is adjusted to 9 with 30% alkali solution. After adjusting the pH, cooling water is introduced to lower the temperature. The mixture is stirred until crystals precipitate. The material is then filtered and washed at approximately 45°C. The washed material is dried to obtain 36.36g of 2-chloro-4-methanesulfonyltoluene.

[0031] S6: 2-Chloro-4-methanesulfonyltoluene was then oxidized with nitric acid to directly yield 32.72 g of 2-chloro-4-methanesulfonylbenzoic acid, with a yield of 64.2%.

[0032] Example 2:

[0033] S1: Add 50g of chlorosulfonic acid to a 500ml four-necked flask using a constant dropping method. Turn on the stirrer at 350rpm and add 1.5g of ammonium chloride. After the ammonium chloride is added, slowly add 55g of o-chlorotoluene dropwise into the flask, controlling the temperature inside the flask at 58℃. The o-chlorotoluene is added over 2 hours. After the addition is complete, maintain the system at this temperature for 2 hours, then take a sample for monitoring. The reaction is then complete.

[0034] S2: Add 50g of tap water to another 500ml four-necked flask and cool it to 5℃. Slowly add the material from S1 dropwise into the flask, controlling the temperature at 15℃. Hydrolyze and destroy the excess chlorosulfonic acid. The system releases a large amount of heat. After the dropwise addition is complete, the heat release ends. Stir for 1 hour and then stop.

[0035] S3: After hydrolyzing and destroying chlorosulfonic acid, 80g of dichloromethane was added for extraction. The mixture was allowed to stand and separate into layers. The lower organic phase was concentrated under reduced pressure, cooled to <10℃, and stirred for 1 hour. The mixture was then discharged and filtered. The white crystals obtained were the product 3-chloro-4-methylbenzenesulfonyl chloride. The mother liquor was concentrated and the above operation was repeated to obtain a secondary product, which could be mixed and used. Finally, the mother liquor was concentrated to remove the solvent, yielding the oil phase byproduct 2-methyl-3-chlorobenzenesulfonyl chloride.

[0036] S4: Add 80g of tap water to another 500ml four-necked flask, start stirring at 350rpm, heat to 45℃, add 22g of sodium sulfite and 19g of sodium carbonate, heat to 70℃, and slowly add 35g of 3-chloro-4-methylbenzenesulfonyl chloride in batches, maintaining the temperature at 77℃ during the addition process. After the addition is complete, keep it at this temperature for one hour; take a sample for monitoring, and the reaction is complete.

[0037] S5: After the reaction is complete, the reaction solution is filtered while hot, and the mother liquor is directly transferred to a 1L high-pressure reactor. After nitrogen purging, it is then purged with chloromethane. Chloromethane is introduced and the pressure is adjusted. When no more gas is introduced and the pressure inside the reactor stops decreasing, the reactor is kept at this temperature for 30 minutes. The reaction is considered complete when the pressure inside the reactor remains constant. The material is then transferred to a 1L four-necked flask. The pH is adjusted to 9 using 30% alkali solution. After adjusting the pH, cooling water is introduced to lower the temperature, and the mixture is stirred until crystals precipitate. The material is then filtered and washed at approximately 45°C. The washed material is dried to obtain 39.76g of 2-chloro-4-methanesulfonyltoluene.

[0038] S6: 35.78 g of 2-chloro-4-methanesulfonyltoluene was directly obtained by nitric acid oxidation, yielding 70.2%.

[0039] Example 3:

[0040] S1: Add 55g of chlorosulfonic acid to a 500ml four-necked flask using a constant dropping method. Turn on the stirrer at 350rpm and add 1.5g of ammonium chloride. After the ammonium chloride is added, slowly add 55g of o-chlorotoluene dropwise into the flask, controlling the temperature inside the vessel at 57℃. The o-chlorotoluene is added over 2.5 hours. After the addition is complete, maintain the system at this temperature for 2 hours, then take a sample for monitoring. The reaction is then complete.

[0041] S2: Add 55g of tap water to another 500ml four-necked flask and cool it to 5℃. Slowly add the material from S1 dropwise into the flask, controlling the temperature at 15℃. Hydrolyze and destroy the excess chlorosulfonic acid. The system releases a large amount of heat. After the dropwise addition is complete, the heat release ends. Stir for 1 hour and then stop.

[0042] S3: After hydrolyzing and destroying chlorosulfonic acid, 80g of dichloromethane was added for extraction. The mixture was allowed to stand and separate into layers. The lower organic phase was concentrated under reduced pressure, cooled to <10℃, and stirred for 1 hour. The mixture was then discharged and filtered. The white crystals obtained were the product 3-chloro-4-methylbenzenesulfonyl chloride. The mother liquor was concentrated and the above operation was repeated to obtain a secondary product, which could be mixed and used. Finally, the mother liquor was concentrated to remove the solvent, yielding the oil phase byproduct 2-methyl-3-chlorobenzenesulfonyl chloride.

[0043] S4: Add 80g of tap water to another 500ml four-necked flask, start stirring at 350rpm, heat to 45℃, add 25g of sodium sulfite and 20g of sodium carbonate, heat to 70℃, slowly add 35g of 3-chloro-4-methylbenzenesulfonyl chloride in batches, maintain the temperature at 77℃ during the addition process, and keep at this temperature for one hour after the addition is complete; take a sample for control, and the reaction is complete.

[0044] S5: After the reaction is complete, the reaction solution is filtered while hot, and the mother liquor is directly transferred to a 1L high-pressure reactor. After nitrogen purging, it is then purged with chloromethane. Chloromethane is introduced initially, and the pressure is adjusted. When no more gas is introduced and the pressure inside the reactor stops decreasing, the reactor is kept at this temperature for 30 minutes. The reaction is considered complete when the pressure inside the reactor remains constant. The material is then transferred to a 1L four-necked flask. The pH is adjusted to 9 using 30% alkali solution. After pH adjustment, cooling water is introduced, and the mixture is stirred until crystals precipitate. The material is then filtered and washed at approximately 45°C. The washed material is dried to obtain 40.88g of 2-chloro-4-methanesulfonyltoluene. Liquid chromatography analysis shows a normalized purity of 98.59%, meeting the process quality standards. The chromatogram is shown below. Figure 1 .

[0045] S6: 2-Chloro-4-methanesulfonyltoluene was directly oxidized with nitric acid to obtain 37.15 g of 2-chloro-4-methanesulfonylbenzoic acid, with a yield of 72.88%. Liquid chromatography analysis showed a normalized purity of 99.52%, meeting the process quality standards. The chromatogram is shown below. Figure 2 .

[0046] The embodiments described above are merely examples of several implementations of the present invention, and while the descriptions are relatively specific and detailed, they should not be construed as limiting the scope of the present invention. It should be noted that those skilled in the art can make various modifications and improvements without departing from the concept of the present invention, and these all fall within the scope of protection of the present invention. Therefore, the scope of protection of this patent should be determined by the appended claims.

Claims

1. A method for synthesizing 2-chloro-4-methanesulfonylbenzoic acid, characterized in that: Includes the following steps: S1: Add chlorosulfonic acid to the reaction vessel, start the stirrer at 300-400 rpm, slowly add ammonium chloride, and after the ammonium chloride is added, slowly add o-chlorotoluene dropwise into the bottle, control the temperature inside the bottle at 55-60℃, and add o-chlorotoluene dropwise for 1.5-2.5 hours. After the dropwise addition is complete, keep the system at this temperature for 2 hours to complete the reaction. S2: Add tap water to another reaction flask in advance and cool it to 0-5℃. Slowly add the product from S1 dropwise to the flask, controlling the temperature at 10-20℃. Hydrolyze and destroy the excess chlorosulfonic acid. The system releases a lot of heat. After the dropwise addition is complete, the heat release ends. Stop stirring after 1 hour. S3: After hydrolyzing and destroying chlorosulfonic acid, dichloromethane solvent is added for extraction. A small amount of water is added to the mixture for washing and filtration. The crystals after filtration are the product 3-chloro-4-methylbenzenesulfonyl chloride. The mother liquor is filtered and allowed to stand to separate into layers. The upper layer is an oil layer, the middle layer is an acidic water layer, and the lower layer is the by-product 2-methyl-3-chlorobenzenesulfonyl chloride. S4: Add water to a new reaction flask, heat to 45°C, turn on the stirrer at 300-400 rpm, add sodium sulfite and sodium carbonate, heat to 70°C, slowly add 3-chloro-4-methylbenzenesulfonyl chloride in batches, maintain the temperature at 76-78°C during the addition process, and keep at this temperature for one hour after the addition is complete. S5: After heat preservation, filter while hot, and transfer the mother liquor into a high-pressure reactor. Replace the air in the reactor three times with nitrogen, and then replace the nitrogen in the reactor three times with chloromethane. Start purging chloromethane and adjust the pressure. When the gas stops being introduced and the pressure in the reactor stops decreasing, keep it at the heat for 30 minutes. Confirm that the pressure in the reactor remains unchanged, then the reaction is complete. Transfer the material to a flask and adjust the pH to 9 with 30% liquid alkali. After adjusting the pH, start cooling with cooling water and stir until crystals precipitate. At about 45°C, filter and wash the material. Dry the washed material to obtain 2-chloro-4-methanesulfonyltoluene. S6: 2-Chloro-4-methanesulfonyltoluene is further oxidized with nitric acid to obtain the product 2-chloro-4-methanesulfonylbenzoic acid; The reaction equation is as follows:

2. The method for synthesizing 2-chloro-4-methanesulfonylbenzoic acid according to claim 1, characterized in that: In S1, the mass ratio of chlorosulfonic acid, ammonium chloride, and o-chlorotoluene is 0.8–1:0.02–0.03:

1.

3. The method for synthesizing 2-chloro-4-methanesulfonylbenzoic acid according to claim 1, characterized in that: The ratio of process water to chlorosulfonic acid used in S2 is 1:

1.

4. The method for synthesizing 2-chloro-4-methanesulfonylbenzoic acid according to claim 1, characterized in that: The solvent used in S3 is one of dichloromethane, dichloroethane, chloroform, toluene, and ethyl acetate.

5. The method for synthesizing 2-chloro-4-methanesulfonylbenzoic acid according to claim 1, characterized in that: The mass ratio of water, sodium sulfite, sodium carbonate, and 3-chloro-4-methylbenzenesulfonyl chloride in S4 is 2.25–2.30: 0.62–0.72: 0.51–0.58:

1.

6. The method for synthesizing 2-chloro-4-methanesulfonylbenzoic acid according to claim 1, characterized in that: The pressure adjustment range in S5 is 0.5 to 0.55 MPa.

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