A method for synthesizing 5-chloro-2-(2-chloroethoxy)benzenesulfonamide

Abstract

The present invention relates to the technical field of chemical synthesis, and provides a method for synthesizing 5-chloro-2-(2-chloroethoxy)benzenesulfonamide. The method comprises: performing an amination reaction on 5-chloro-2-(2-chloroethoxy)benzenesulfonyl chloride and aqueous ammonia to obtain 5-chloro-2-(2-chloroethoxy)benzenesulfonamide. The above technical solution solves the problems of incomplete amination, unstable product quality, and subsequent deactivation of a hydrogenation catalyst in the production process of 5-chloro-2-(2-chloroethoxy)benzenesulfonamide in the related art, while also solving the problems of low product yield and high production and processing costs.

Description

Technical Field

[0001] The present invention relates to the technical field of chemical synthesis, and in particular to a method for synthesizing 5-chloro-2-(2-chloroethoxy)benzenesulfonamide. Background Art

[0002] Sulfonylurea herbicides are "super-efficient" pesticides, boasting broad spectrum control, strong selectivity, ease of use, safety for mammals, and easy decomposition in the environment. my country is a major producer and user of sulfonylurea herbicides, and these herbicides have played a significant role in increasing crop yields and incomes. Fentasulfuron-methyl, a sulfonylurea herbicide and a side-chain amino acid synthesis inhibitor, is widely recognized in the market for its effectiveness, crop safety, and application time flexibility regardless of weed growth stage.

[0003] 5-Chloro-2-(2-chloroethoxy)benzenesulfonamide (C8H9O3Cl2NS) is an important intermediate of bensulfuron-methyl, and its structural formula is as follows:

[0004]

[0005] In the existing production process of 5-chloro-2-(2-chloroethoxy)benzenesulfonamide, amination is generally performed using ammonia. However, the amination is not complete, and unreacted acyl chloride remains in the product, which in turn affects the activity of the catalyst in the subsequent hydrogenation reaction, resulting in deactivation of the subsequent hydrogenation catalyst and failure to produce 2-(2-chloroethoxy)benzenesulfonamide. At the same time, the product yield is low. In addition, because excessive ammonia needs to be continuously introduced into the reaction system, ammonia is seriously wasted, which not only increases the production cost but also the cost of three wastes treatment, which is not conducive to the clean production of the product.

[0006] Therefore, it is urgent to find a green, environmentally friendly, high-yield, and easy-to-operate amination method that avoids residual 5-chloro-2-(2-chloroethoxy)benzenesulfonyl chloride in the amination process, while reducing the waste of raw materials and lowering production costs. Summary of the Invention

[0007] The present invention provides a method for synthesizing 5-chloro-2-(2-chloroethoxy)benzenesulfonamide. This method solves the problems of incomplete amination, unstable product quality, and subsequent deactivation of the hydrogenation catalyst, which prevent the production of 2-(2-chloroethoxy)benzenesulfonamide, in the production process of 5-chloro-2-(2-chloroethoxy)benzenesulfonamide in the related art. The method also solves the problems of low product yield and high production and processing costs. The technical solution of the present invention is as follows:

[0008] A method for synthesizing 5-chloro-2-(2-chloroethoxy)benzenesulfonamide comprises the following steps: subjecting 5-chloro-2-(2-chloroethoxy)benzenesulfonyl chloride and aqueous ammonia to an amination reaction to obtain 5-chloro-2-(2-chloroethoxy)benzenesulfonamide.

[0009] As a further technical solution, the solvent for the amination reaction is 1,2-dichloroethane, and the molar ratio of the 5-chloro-2-(2-chloroethoxy)benzenesulfonyl chloride to 1,2-dichloroethane is 1:10-20.

[0010] As a further technical solution, the mass fraction of the ammonia water is 20%.

[0011] As a further technical solution, the molar ratio of 5-chloro-2-(2-chloroethoxy)benzenesulfonyl chloride to ammonia water is 1:1-2.

[0012] As a further technical solution, the amination reaction temperature is 30-40° C. and the reaction time is 4-6 hours.

[0013] As a further technical solution, the 5-chloro-2-(2-chloroethoxy)benzenesulfonyl chloride is obtained by chlorosulfonating 1-chloro-4-(2-chloroethoxy)benzene.

[0014] As a further technical solution, the chlorosulfonation reaction is specifically as follows: after dissolving 1-chloro-4-(2-chloroethoxy)benzene, a chlorosulfonating agent and DMF are added dropwise and then refluxed to carry out the chlorosulfonation reaction.

[0015] As a further technical solution, the solvent used for the dissolution is 1,2-dichloroethane, and the molar ratio of the 1-chloro-4-(2-chloroethoxy)benzene to 1,2-dichloroethane is 1:10-20.

[0016] As a further technical solution, the chlorosulfonating agent includes chlorosulfonic acid and thionyl chloride.

[0017] As a further technical solution, the molar ratio of the 1-chloro-4-(2-chloroethoxy)benzene, chlorosulfonic acid, thionyl chloride and DMF is 1:1 to 1.5:1 to 1.5:0.51.

[0018] As a further technical solution, the molar ratio of 1-chloro-4-(2-chloroethoxy)benzene, chlorosulfonic acid, thionyl chloride and DMF is 1:1.23:1.28:0.51.

[0019] As a further technical solution, the dropping temperature is 30-40°C.

[0020] As a further technical solution, the time for adding chlorosulfonic acid is 2 to 3 hours, the time for adding thionyl chloride is 10 to 20 minutes, and the time for adding DMF is 1 to 2 hours.

[0021] As a further technical solution, the time for adding chlorosulfonic acid is 2.5 hours, the time for adding thionyl chloride is 15 minutes, and the time for adding DMF is 1.5 hours.

[0022] As a further technical solution, the chlorosulfonation reaction temperature is 75-85° C. and the reaction time is 8-10 hours.

[0023] As a further technical solution, the 1-chloro-4-(2-chloroethoxy)benzene is prepared by the following method: p-chlorophenol, 1,2-dichloroethane, potassium hydroxide and water are mixed and reacted to obtain 1-chloro-4-(2-chloroethoxy)benzene.

[0024] As a further technical solution, the reaction temperature is 70-80° C. and the reaction time is 14-18 hours.

[0025] As a further technical solution, the molar ratio of p-chlorophenol, 1,2-dichloroethane, potassium hydroxide and water is 1:3-4:1-2:6-8.

[0026] As a further technical solution, after the amination reaction, purification is further included, specifically, the product obtained by the amination reaction is dissolved and then purified using hydrogen peroxide.

[0027] As a further technical solution, the solvent used for the dissolution is acetone, and the mass ratio of the product to acetone is 1:3-5.

[0028] As a further technical solution, the mass ratio of the product to acetone is 1:4.

[0029] As a further technical solution, the mass fraction of the hydrogen peroxide is 30%.

[0030] As a further technical solution, the mass ratio of the product to hydrogen peroxide is 1:0.01 to 0.08.

[0031] As a further technical solution, the mass ratio of the product to hydrogen peroxide is 1:0.03.

[0032] As a further technical solution, the refining temperature is 50-60° C. and the time is 1-3 hours.

[0033] The working principle and beneficial effects of the present invention are:

[0034] The present invention provides a method for synthesizing 5-chloro-2-(2-chloroethoxy)benzenesulfonamide, and the obtained yield reaches more than 53%. Through the above technical scheme, the problems of harsh reaction conditions, low finished product qualification rate, low product yield, and high production cost and processing cost in the amination stage using ammonia in the prior art are solved, the qualification rate and output of the product are improved, and the production and processing costs are reduced. DETAILED DESCRIPTION

[0035] The following will be combined with the embodiments of the present invention to clearly and completely describe the technical solutions in the embodiments of the present invention. Obviously, the embodiments described are only part of the embodiments of the present invention, not all of the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without making any creative efforts are within the scope of protection of the present invention.

[0036] Experimental Group 1

[0037] S1. Add water (100 g, 5.56 mol) to a 500 mL three-necked flask, start stirring and add potassium hydroxide (63 g, 1.125 mol), add 1,2-dichloroethane (285 g, 2.88 mol) and p-chlorophenol (100 g, 0.78 mol) after dissolution, heat to 76 ° C and reflux for 16 h, terminate the reaction and let it stand for 20 min before settling, wash the 1,2-dichloroethane layer twice with 500 mL of water to pH = 7, remove the solvent 1,2-dichloroethane, and obtain 1-chloro-4-(2-chloroethoxy)benzene (82 g, 0.43 mol); add hydrochloric acid to the water layer to adjust the pH to 2, and recover unreacted p-chlorophenol (41.76 g, 0.32 mol);

[0038] S2. Add 1,2-dichloroethane (660 g, 6.67 mol) and 1-chloro-4-(2-chloroethoxy)benzene (82 g, 0.43 mol) into a 1000 mL three-necked flask, stir and heat to 35 ° C, slowly add chlorosulfonic acid (62.02 g, 0.53 mol) into the three-necked flask and add it in 2.5 hours. Control the addition temperature at 35 ° C. After adding chlorosulfonic acid, keep it warm for 2 hours. After the insulation is completed, add thionyl chloride (65.9 g, 0.55 mol) ol) was added over 15 min, and DMF (16.3 g, 0.22 mol) was added dropwise over 1.5 h. After the addition of DMF, the mixture was kept warm for 20 min, the temperature was raised to 85 ° C and refluxed, and maintained at reflux for 8 h, cooled to 0 ° C, and a solution of 5-chloro-2-(2-chloroethoxy)benzenesulfonyl chloride (124.5 g, 0.43 mol) in 1,2-dichloroethane (650 g, 6.57 mol) was washed three times with water to a pH value of 7;

[0039] S3. Add 20 wt% ammonia water (120 g, 0.69 mol) to a 1000 mL three-necked flask, add dropwise a solution of 5-chloro-2-(2-chloroethoxy)benzenesulfonyl chloride in 1,2-dichloroethane at 35°C, keep warm for 5 h after the addition, cool to 0°C, filter out the solid, and dry it to obtain 5-chloro-2-(2-chloroethoxy)benzenesulfonamide, with a solid mass of 115 g.

[0040] This experimental group conducted a hydrogenation experiment. 50 g of 5-chloro-2-(2-chloroethoxy)benzenesulfonamide, 100 mL of acetone, 20 mL of water, 22.5 g of sodium bicarbonate, and 1 g of Pd / C (Pd content 3 wt%) were added to an autoclave, pressurized to 1 MPa, and heated to 60°C. The pressure was maintained at 1 MPa until the pressure stopped decreasing. The Pd / C was then cooled and filtered out. The filtrate was then added with water to precipitate a solid for detection.

[0041] The results showed that no 2-(2-chloroethoxy)benzenesulfonamide was generated and the catalyst Pd / C was deactivated.

[0042] Experimental Group 2

[0043] S1. Add water (100 g, 5.56 mol) to a 500 mL three-necked flask, start stirring and add potassium hydroxide (63 g, 1.125 mol), add 1,2-dichloroethane (285 g, 2.88 mol) and p-chlorophenol (100 g, 0.78 mol) after dissolution, heat to 76 ° C and reflux for 16 h, terminate the reaction and let it stand for 20 min before settling, wash the 1,2-dichloroethane layer twice with 500 mL of water to pH = 7, remove the solvent 1,2-dichloroethane, and obtain 1-chloro-4-(2-chloroethoxy)benzene (82 g, 0.43 mol); add hydrochloric acid to the water layer to adjust the pH to 2, and recover unreacted p-chlorophenol (41.76 g, 0.32 mol);

[0044] S2. Add 1,2-dichloroethane (660 g, 6.67 mol) and 1-chloro-4-(2-chloroethoxy)benzene (82 g, 0.43 mol) into a 1000 mL three-necked flask, stir and heat to 35 ° C, slowly add chlorosulfonic acid (62.02 g, 0.53 mol) into the three-necked flask and add it in 2.5 hours. Control the addition temperature at 35 ° C. After adding chlorosulfonic acid, keep it warm for 2 hours. After the insulation is completed, add thionyl chloride (65.9 g, 0.55 mol) ol) was added over 15 min, and DMF (16.3 g, 0.22 mol) was added dropwise over 1.5 h. After the addition of DMF, the mixture was kept warm for 20 min, the temperature was raised to 85 ° C and refluxed, and maintained at reflux for 8 h, cooled to 0 ° C, and a solution of 5-chloro-2-(2-chloroethoxy)benzenesulfonyl chloride (124.5 g, 0.43 mol) in 1,2-dichloroethane (650 g, 6.57 mol) was washed three times with water to a pH value of 7;

[0045] S3. Add 20 wt% ammonia water (120 g, 0.69 mol) to a 1000 mL three-necked flask, add dropwise a solution of 5-chloro-2-(2-chloroethoxy)benzenesulfonyl chloride in 1,2-dichloroethane at 35°C, keep warm for 5 h after the addition, cool to 0°C, and filter out the solid, which is 5-chloro-2-(2-chloroethoxy)benzenesulfonamide, with a solid mass of 115 g.

[0046] S4, 5-chloro-2-(2-chloroethoxy)benzenesulfonamide was dissolved in 460g of acetone, heated to 55°C and refluxed for 2h, cooled to 0°C, 500g of water was added, the solid was filtered off and dried to obtain 5-chloro-2-(2-chloroethoxy)benzenesulfonamide after recrystallization, with a solid mass of 113g;

[0047] This experimental group conducted a hydrogenation experiment. 50 g of 5-chloro-2-(2-chloroethoxy)benzenesulfonamide, 100 mL of acetone, 20 mL of water, 22.5 g of sodium bicarbonate, and 1 g of Pd / C (Pd content 3 wt%) were added to an autoclave, pressurized to 1 MPa, and heated to 60°C. The pressure was maintained at 1 MPa until the pressure stopped decreasing. The Pd / C was then cooled and filtered out. The filtrate was then added with water to precipitate a solid for detection.

[0048] The results showed that no 2-(2-chloroethoxy)benzenesulfonamide was generated and the catalyst Pd / C was deactivated.

[0049] Experimental Group 3

[0050] S1. Add water (100 g, 5.56 mol) to a 500 mL three-necked flask, start stirring and add potassium hydroxide (63 g, 1.125 mol), add 1,2-dichloroethane (285 g, 2.88 mol) and p-chlorophenol (100 g, 0.78 mol) after dissolution, heat to 76 ° C and reflux for 16 h, terminate the reaction and let it stand for 20 min before settling, wash the 1,2-dichloroethane layer twice with 500 mL of water to pH = 7, remove the solvent 1,2-dichloroethane, and obtain 1-chloro-4-(2-chloroethoxy)benzene (82 g, 0.43 mol); add hydrochloric acid to the water layer to adjust the pH to 2, and recover unreacted p-chlorophenol (41.76 g, 0.32 mol);

[0051] S2. Add 1,2-dichloroethane (660 g, 6.67 mol) and 1-chloro-4-(2-chloroethoxy)benzene (82 g, 0.43 mol) into a 1000 mL three-necked flask, stir and heat to 35 ° C, slowly add chlorosulfonic acid (62.02 g, 0.53 mol) into the three-necked flask and add it in 2.5 hours. Control the addition temperature at 35 ° C. After adding chlorosulfonic acid, keep it warm for 2 hours. After the insulation is completed, add thionyl chloride (65.9 g, 0.55 mol) ol) was added over 15 min, and DMF (16.3 g, 0.22 mol) was added dropwise over 1.5 h. After the addition of DMF, the mixture was kept warm for 20 min, the temperature was raised to 85 ° C and refluxed, and maintained at reflux for 8 h, cooled to 0 ° C, and a solution of 5-chloro-2-(2-chloroethoxy)benzenesulfonyl chloride (124.5 g, 0.43 mol) in 1,2-dichloroethane (650 g, 6.57 mol) was washed three times with water to a pH value of 7;

[0052] S3. Add 20 wt% ammonia water (120 g, 0.69 mol) to a 1000 mL three-necked flask, add dropwise a solution of 5-chloro-2-(2-chloroethoxy)benzenesulfonyl chloride in 1,2-dichloroethane at 35°C, keep warm for 5 h after the addition, cool to 0°C, and filter out the solid, which is 5-chloro-2-(2-chloroethoxy)benzenesulfonamide, with a solid mass of 115 g.

[0053] S4, 5-chloro-2-(2-chloroethoxy)benzenesulfonamide was dissolved in 460g of acetone, 10g of 30wt% hydrogen peroxide was added dropwise at room temperature, the temperature was raised to 55°C and refluxed for 2h, the temperature was lowered to 0°C, 500g of water was added, the solid was filtered off and dried to obtain 5-chloro-2-(2-chloroethoxy)benzenesulfonamide after recrystallization, with a solid mass of 113g;

[0054] This experimental group conducted a hydrogenation experiment. 50 g of 5-chloro-2-(2-chloroethoxy)benzenesulfonamide, 100 mL of acetone, 20 mL of water, 22.5 g of sodium bicarbonate, and 1 g of Pd / C (Pd content 3 wt%) were added to an autoclave, pressurized to 1 MPa, and heated to 60°C. The pressure was maintained at 1 MPa until the pressure stopped decreasing. The Pd / C was then cooled and filtered out. The filtrate was then added with water to precipitate a solid for detection.

[0055] The mass of 2-(2-chloroethoxy)benzenesulfonamide was 43 g, the content was 99%, and the remaining amount of 5-chloro-2-(2-chloroethoxy)benzenesulfonamide was 0.1%. The catalyst Pd / C was not deactivated, and the hydrogenation was successful.

[0056] Example 1

[0057] S1. Add water (100 g, 5.56 mol) to a 500 mL three-necked flask, start stirring and add potassium hydroxide (63 g, 1.125 mol), add 1,2-dichloroethane (285 g, 2.88 mol) and p-chlorophenol (100 g, 0.78 mol) after dissolution, heat to 76 ° C and reflux for 16 h, terminate the reaction and let it stand for 20 min before settling, wash the 1,2-dichloroethane layer twice with 500 mL of water to pH = 7, remove the solvent 1,2-dichloroethane, and obtain 1-chloro-4-(2-chloroethoxy)benzene (82 g, 0.43 mol); add hydrochloric acid to the water layer to adjust the pH to 2, and recover unreacted p-chlorophenol (41.76 g, 0.32 mol);

[0058] S2. Add 1,2-dichloroethane (660 g, 6.67 mol) and 1-chloro-4-(2-chloroethoxy)benzene (82 g, 0.43 mol) into a 1000 mL three-necked flask, stir and heat to 35 ° C, then slowly add chlorosulfonic acid (62.02 g, 0.53 mol) into the three-necked flask and finish adding it within 2.5 h. Control the addition temperature at 35 ° C. After adding chlorosulfonic acid, keep the temperature for 2 h. After the temperature is completely kept, add thionyl chloride (65.9 g, 0.55 mol) ol) was added over 15 min, and DMF (16.3 g, 0.22 mol) was added dropwise over 1.5 h. After the addition of DMF, the mixture was kept warm for 20 min, the temperature was raised to 85 ° C and refluxed, and maintained at reflux for 8 h, cooled to 0 ° C, and a solution of 5-chloro-2-(2-chloroethoxy)benzenesulfonyl chloride (124.5 g, 0.43 mol) in 1,2-dichloroethane (650 g, 6.57 mol) was washed three times with water to a pH value of 7;

[0059] S3. Add 20 wt% ammonia water (120 g, 0.69 mol) to a 1000 mL three-necked flask, add dropwise a solution of 5-chloro-2-(2-chloroethoxy)benzenesulfonyl chloride in 1,2-dichloroethane at 32°C, keep the mixture warm for 5 h, cool to 0°C, and filter out the solid, which is 5-chloro-2-(2-chloroethoxy)benzenesulfonamide. The solid mass is 110.02 g.

[0060] S4. 5-chloro-2-(2-chloroethoxy)benzenesulfonamide was dissolved in 460 g of acetone, 10 g of 30 wt% hydrogen peroxide was added dropwise at room temperature, the mixture was heated to 55 ° C and refluxed for 2 h, then cooled to 0 ° C, 500 g of water was added, the solid was filtered off and dried to obtain 5-chloro-2-(2-chloroethoxy)benzenesulfonamide after recrystallization, with a solid mass of 105.25 g and a content of 99.05%.

[0061] Example 2

[0062] S1, S2, and S4 were the same as in Example 1, except that the addition temperature in S3 was changed to 35° C. S3 yielded 115.22 g of 5-chloro-2-(2-chloroethoxy)benzenesulfonamide, and S4 yielded 113.76 g of 5-chloro-2-(2-chloroethoxy)benzenesulfonamide, with a solid mass of 99.27%.

[0063] Example 3

[0064] S1, S2, and S4 were the same as in Example 1, except that the addition temperature in S3 was changed to 37° C. S3 yielded 115.02 g of 5-chloro-2-(2-chloroethoxy)benzenesulfonamide, and S4 yielded 113.66 g of 5-chloro-2-(2-chloroethoxy)benzenesulfonamide, with a solid mass of 99.25%.

[0065] Example 4

[0066] S1, S2, and S4 were the same as in Example 2, except that the holding time in S3 was changed to 3 h. S3 yielded 111.23 g of 5-chloro-2-(2-chloroethoxy)benzenesulfonamide, and S4 yielded 102.57 g of 5-chloro-2-(2-chloroethoxy)benzenesulfonamide, with a solid mass of 98.11% and a content of 5-chloro-2-(2-chloroethoxy)benzenesulfonamide.

[0067] Example 5

[0068] S1, S2, and S4 were the same as in Example 2, except that the holding time in S3 was changed to 7 h. S3 yielded 115.25 g of 5-chloro-2-(2-chloroethoxy)benzenesulfonamide, and S4 yielded 113.59 g of 5-chloro-2-(2-chloroethoxy)benzenesulfonamide, with a solid mass of 99.31% and a content of 5-chloro-2-(2-chloroethoxy)benzenesulfonamide.

[0069] Example 6

[0070] S1, S2, and S4 were identical to those in Example 2, except that the amount of 20 wt% aqueous ammonia added in S3 was changed to 130 g. S3 yielded 115.02 g of 5-chloro-2-(2-chloroethoxy)benzenesulfonamide, and S4 yielded 113.41 g of 5-chloro-2-(2-chloroethoxy)benzenesulfonamide, with a solid mass of 99.26% and a content of 5-chloro-2-(2-chloroethoxy)benzenesulfonamide.

[0071] Example 7

[0072] S1, S2, and S4 were identical to those in Example 2, except that the amount of 20 wt% aqueous ammonia added in S3 was changed to 110 g. S3 yielded 110.88 g of 5-chloro-2-(2-chloroethoxy)benzenesulfonamide, and S4 yielded 107.25 g of 5-chloro-2-(2-chloroethoxy)benzenesulfonamide, with a solid mass of 98.76% and a content of 98.76%.

[0073] Example 8

[0074] S1, S2, and S3 were the same as in Example 2, except that the amount of 30 wt% hydrogen peroxide added in S4 was changed to 8 g. S3 yielded 115.25 g of 5-chloro-2-(2-chloroethoxy)benzenesulfonamide, and S4 yielded 113.52 g of 5-chloro-2-(2-chloroethoxy)benzenesulfonamide, with a solid mass of 98.71% and a content of 98.71%.

[0075] Example 9

[0076] S1, S2, and S3 were identical to those in Example 2, except that the amount of 30 wt% hydrogen peroxide added in S4 was changed to 12 g. S3 yielded 115.21 g of 5-chloro-2-(2-chloroethoxy)benzenesulfonamide, and S4 yielded 112.88 g of 5-chloro-2-(2-chloroethoxy)benzenesulfonamide, with a solid mass of 99.33% and a content of 5-chloro-2-(2-chloroethoxy)benzenesulfonamide.

[0077] Example 10

[0078] S1. Add water (84.24 g, 4.68 mol) to a 500 mL three-necked flask, start stirring and add potassium hydroxide (43.68 g, 0.78 mol), add 1,2-dichloroethane (231.66 g, 2.34 mol) and p-chlorophenol (100 g, 0.78 mol) after dissolution, heat to 70 ° C and reflux for 18 h, terminate the reaction and let it stand for 20 min before settling, wash the 1,2-dichloroethane layer twice with 500 mL of water to pH = 7, remove the solvent 1,2-dichloroethane, and obtain 1-chloro-4-(2-chloroethoxy)benzene (57.2 g, 0.3 mol); add hydrochloric acid to the water layer to adjust the pH to 2, and recover unreacted p-chlorophenol (60.12 g, 0.47 mol);

[0079] S2. Add 1,2-dichloroethane (297 g, 3.0 mol) and 1-chloro-4-(2-chloroethoxy)benzene (57.2 g, 0.3 mol) into a 1000 mL three-necked flask, stir and heat to 30 °C, then slowly add chlorosulfonic acid (35.1 g, 0.3 mol) into the three-necked flask and finish the addition within 2 h. Control the addition temperature at 30 °C. After adding chlorosulfonic acid, keep the temperature for 2 h. After the temperature is completely maintained, add thionyl chloride (35.7 g, 0.3 mol) l) Add the mixture over 10 minutes, then continue to add DMF (11.2 g, 0.15 mol) dropwise over 1 hour. After the addition of DMF, heat for 20 minutes, raise the temperature to 75°C and reflux, maintain reflux for 10 hours, cool to 0°C, and wash a solution of 5-chloro-2-(2-chloroethoxy)benzenesulfonyl chloride (86.88 g, 0.3 mol) in 1,2-dichloroethane (290 g, 2.93 mol) with water three times to a pH of 7;

[0080] S3. Add 20 wt% ammonia water (52.5 g, 0.3 mol) to a 1000 mL three-necked flask, and add dropwise a solution of 5-chloro-2-(2-chloroethoxy)benzenesulfonyl chloride (86.88 g, 0.3 mol) in 1,2-dichloroethane (290 g, 2.93 mol) at 30°C. After the addition is complete, keep the mixture warm for 6 h, cool to 0°C, and filter out the solid, which is 5-chloro-2-(2-chloroethoxy)benzenesulfonamide, with a solid mass of 75 g.

[0081] S4. 5-chloro-2-(2-chloroethoxy)benzenesulfonamide was dissolved in 225 g of acetone, 2.5 g of 30 wt% hydrogen peroxide was added dropwise at room temperature, the mixture was heated to 50 ° C and refluxed for 3 h, then cooled to 0 ° C, 500 g of water was added, and the solid was filtered off to obtain 5-chloro-2-(2-chloroethoxy)benzenesulfonamide after recrystallization, with a solid mass of 72.00 g and a content of 98.76%.

[0082] Example 11

[0083] S1. Add water (112.32 g, 6.24 mol) to a 500 mL three-necked flask, start stirring and add potassium hydroxide (87.36 g, 1.56 mol), add 1,2-dichloroethane (308.88 g, 3.12 mol) and p-chlorophenol (100 g, 0.78 mol) after dissolution, heat to 80 ° C and reflux for 14 h, terminate the reaction and let it stand for 20 min before settling, wash the 1,2-dichloroethane layer twice with 500 mL of water to pH = 7, remove the solvent 1,2-dichloroethane, and obtain 1-chloro-4-(2-chloroethoxy)benzene (82 g, 0.43 mol); add hydrochloric acid to the water layer to adjust the pH to 2, and recover unreacted p-chlorophenol (42.35 g, 0.33 mol);

[0084] S2. Add 1,2-dichloroethane (851.4 g, 8.6 mol) and 1-chloro-4-(2-chloroethoxy)benzene (82 g, 0.43 mol) into a 1000 mL three-necked flask, stir and heat to 40 ° C, slowly add chlorosulfonic acid (75.47 g, 0.645 mol) into the three-necked flask and add it within 3 hours. Control the addition temperature at 40 ° C. After adding chlorosulfonic acid, keep the temperature for 2 hours. After the temperature is maintained, add thionyl chloride (76.76 g, 0.64 After the addition of DMF (16.1 g, 0.22 mol) was added dropwise over 2 h, the temperature was kept at 80 ° C for 20 min, and the reflux temperature was raised to 80 ° C, and the reflux temperature was maintained for 9 h, and the mixture was cooled to 0 ° C. A solution of 5-chloro-2-(2-chloroethoxy)benzenesulfonyl chloride (124.5 g, 0.43 mol) in 1,2-dichloroethane (830 g, 8.38 mol) was washed three times with water to a pH value of 7;

[0085] S3. Add 20 wt% ammonia water (150.5 g, 0.86 mol) to a 1000 mL three-necked flask, add dropwise a solution of 5-chloro-2-(2-chloroethoxy)benzenesulfonyl chloride (124.5 g, 0.43 mol) in 1,2-dichloroethane (830 g, 8.38 mol) at 40°C, keep warm for 4 h after the addition, cool to 0°C, and filter out the solid, which is 5-chloro-2-(2-chloroethoxy)benzenesulfonamide, with a solid mass of 110 g;

[0086] S4. 5-chloro-2-(2-chloroethoxy)benzenesulfonamide was dissolved in 550 g of acetone, 29.3 g of 30 wt% hydrogen peroxide was added dropwise at room temperature, the temperature was raised to 60 ° C and refluxed for 1 h, the temperature was lowered to 0 ° C, 500 g of water was added, and the solid was filtered out, which was 5-chloro-2-(2-chloroethoxy)benzenesulfonamide after recrystallization, with a solid mass of 111.50 g and a content of 99.50%.

[0087] The content of 5-chloro-2-(2-chloroethoxy)benzenesulfonamide obtained in Examples 1 to 11 was analyzed by HPLC, and the yield was calculated according to the following formula:

[0088] Yield (%) = (actual solid mass obtained × content of 5-chloro-2-(2-chloroethoxy)benzenesulfonamide) ÷ theoretical value of 5-chloro-2-(2-chloroethoxy)benzenesulfonamide × 100%

[0089] The reaction conditions of Examples 1 to 11 and the content and yield of 5-chloro-2-(2-chloroethoxy)benzenesulfonamide are recorded in Table 1.

[0090] Table 1 Reaction conditions and the content and yield of 5-chloro-2-(2-chloroethoxy)benzenesulfonamide

[0091]

[0092] As can be seen from Table 1, the method for synthesizing 5-chloro-2-(2-chloroethoxy)benzenesulfonamide provided by the present invention has a 5-chloro-2-(2-chloroethoxy)benzenesulfonamide content of more than 98.11% and a yield of more than 33.87%.

[0093] Compared with Example 2, the amination temperature in Example 1 is lower, and the amination temperature in Example 3 is higher. The yield and content of 5-chloro-2-(2-chloroethoxy)benzenesulfonamide obtained in Examples 1 and 3 are lower than those in Example 2. This indicates that when the amination reaction temperature is 35°C, the yield and content of 5-chloro-2-(2-chloroethoxy)benzenesulfonamide are optimal.

[0094] Compared with Example 2, the amination time in Example 4 is shortened, and the amination time in Example 5 is increased. The yield and content of 5-chloro-2-(2-chloroethoxy)benzenesulfonamide obtained in Example 4 are lower than those in Example 2. Although the content of 5-chloro-2-(2-chloroethoxy)benzenesulfonamide obtained in Example 5 is higher than that in Example 2, the final yield is lower than that in Example 2.

[0095] Compared with Example 2, the amount of ammonia water used in the amination reaction was increased in Example 6, and the amount of ammonia water used in the amination reaction was reduced in Example 7. The yield and content of 5-chloro-2-(2-chloroethoxy)benzenesulfonamide obtained in Examples 6 and 7 were lower than those in Example 2. This indicates that the yield and content of 5-chloro-2-(2-chloroethoxy)benzenesulfonamide obtained were the highest when the mass of 20 wt% ammonia water was 120 g.

[0096] Compared with Example 2, the amount of hydrogen peroxide used in the refining process was reduced in Example 8, and the amount of hydrogen peroxide used in the refining process was increased in Example 9. The content and yield of 5-chloro-2-(2-chloroethoxy)benzenesulfonamide obtained in Example 8 were lower than those in Example 2, and the content of 5-chloro-2-(2-chloroethoxy)benzenesulfonamide obtained in Example 9 was higher than that in Example 2, but the yield was lower than that in Example 2.

[0097] The above are only preferred embodiments of the present invention and are not intended to limit the present invention. Any modifications, equivalent replacements, improvements, etc. made within the spirit and principles of the present invention should be included in the scope of protection of the present invention.

Claims

1. A method for synthesizing 5-chloro-2-(2-chloroethoxy)benzenesulfonamide, characterized in that: include: 5-chloro-2-(2-chloroethoxy)benzenesulfonyl chloride and ammonia water undergo amination reaction to obtain 5-chloro-2-(2-chloroethoxy)benzenesulfonamide; The 5-chloro-2-(2-chloroethoxy)benzenesulfonyl chloride is obtained by chlorosulfonating 1-chloro-4-(2-chloroethoxy)benzene; The chlorosulfonation reaction is specifically as follows: after dissolving 1-chloro-4-(2-chloroethoxy)benzene, a chlorosulfonating agent and DMF are added dropwise and then refluxed to carry out a chlorosulfonation reaction; The 1-chloro-4-(2-chloroethoxy)benzene is prepared by the following method: p-chlorophenol, 1,2-dichloroethane, potassium hydroxide and water are mixed and reacted to obtain 1-chloro-4-(2-chloroethoxy)benzene; the reaction temperature is 70-80° C. and the reaction time is 14-18 hours; the molar ratio of p-chlorophenol, 1,2-dichloroethane, potassium hydroxide and water is 1:3-4:1-2:6-8; After the amination reaction, the process further includes refining, specifically, dissolving the product obtained by the amination reaction and then refining it using hydrogen peroxide; the solvent used for the dissolution is acetone, and the mass ratio of the product to acetone is 1:3-5; the mass fraction of the hydrogen peroxide is 30%; the mass ratio of the product to hydrogen peroxide is 1:0.01-0.08; the refining temperature is 50-60° C., and the refining time is 1-3 hours.

2. A method for synthesizing 5-chloro-2-(2-chloroethoxy)benzenesulfonamide according to claim 1, characterized in that, The molar ratio of the 5-chloro-2-(2-chloroethoxy)benzenesulfonyl chloride to the ammonia water is 1:1-2.

3. A method for synthesizing 5-chloro-2-(2-chloroethoxy)benzenesulfonamide according to claim 1, characterized in that, The amination reaction temperature is 30-40° C., the reaction time is 4-6 hours, and the mass fraction of ammonia water is 20%.

4. A method for synthesizing 5-chloro-2-(2-chloroethoxy)benzenesulfonamide according to claim 1, characterized in that, The solvents for the amination reaction and the chlorosulfonation reaction are each independently 1,2-dichloroethane; The molar ratio of the 5-chloro-2-(2-chloroethoxy)benzenesulfonyl chloride or 1-chloro-4-(2-chloroethoxy)benzene to 1,2-dichloroethane is independently 1:10-20.

5. A method for synthesizing 5-chloro-2-(2-chloroethoxy)benzenesulfonamide according to claim 1, characterized in that, The chlorosulfonating agent includes chlorosulfonic acid and thionyl chloride.

6. A method for synthesizing 5-chloro-2-(2-chloroethoxy)benzenesulfonamide according to claim 5, characterized in that: The molar ratio of 1-chloro-4-(2-chloroethoxy)benzene, chlorosulfonic acid, thionyl chloride and DMF is 1:1 to 1.5:1 to 1.5:0.51; The dropping temperature is 30-40°C; The time for adding chlorosulfonic acid is 2 to 3 hours, the time for adding thionyl chloride is 10 to 20 minutes, and the time for adding DMF is 1 to 2 hours; The chlorosulfonation reaction temperature is 75-85° C. and the reaction time is 8-10 hours.

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