CS270529B1 - Process for the preparation of N-isopropyl-2,1,3-benzothiadiazin-4-one 2,2-dioxide - Google Patents

Abstract

The present invention concerns the production of N-isopropyl-2,1,3-benzothiadiazin-4-one-2,2-dioxide (bentazone). A dichloroethane solution of N-isopropyl-N-(2-carbmethoxyphenyl)sulfamide is used as the starting material, which is treated with phosphorus oxychloride in an amount of 3 to 7 parts by weight of P0Cl3 per 1 part by weight of water present in the azeotropically dried dichlorosthene solution of N-isopropyl-N-(2-carbmethoxyphenyl)sulfamide. The final product is not required from the point of view of application purification.

Description

The invention relates to a process for the preparation of N-isopropyl-2,1,3-benzothiadiazin-4-one 2,2-dioxide (bentazone) from a solution of N-isopropyl-N * - (2-carbomethoxy) phenylsulfamide by removing residual water after azeotropic drying. and phosphorus oxychloride.

The issue of bentazone synthesis is protected by several patents. Thus, U.S. Pat. No. 2,424,371 describes the preparation of intermediates. The synthesis of bentazone is covered by Example no. 2, which describes the preparation of N-isophenylamidosulfonic acid (an intermediate for the reaction of anthiolic acid or methyl ester) from Ν, Ν'-diisopropylurea. The problem is that these urea derivatives can be prepared from phosgene, and therefore the possibility of practical application of the process is minimal and the technology is extremely demanding. A similar procedure protects DOS 2,852,159 and the disadvantages are similar to those mentioned above. The condensation of isopropylsulfamoyl chloride with anthranilic acid and its methyl ester is described in DOS 2,357,063. This is a simple procedure, but the synthesis of (CH ₃ ) ₂ CHNHSO ₂ Cl, which is not easily feasible from isopropylamine and SO ₂ Cl ₂ , is difficult. For the preparation, for example, a demanding device, which disproportionately increases the investment costs.

According to the invention, the process for the preparation of N-isopropyl-2,1,3-benzothiadiazin-4-one 2,2-dioxide from N-isopropyl-N '- (2-carbomethoxy) phenylsulphamide by treatment with sodium methanolate is carried out by treatment with dichloroethane. the solution of N-isopropyl-N '- (- carbmethoxy) -phenylsulfamide is treated with phosphorus oxychloride in an amount of 3 to 7 parts by weight, preferably 4 to 5 parts by weight, of POCl 3 per 1 part by weight of water present in the azeotropically dried dichloroethane W a solution of N-isopropyl-N '- (2-carbmethoxy) phenylsulfamide.

The main advantages of the process according to the invention include the simple disposal of residual water after azeotropic drying of a dichloroethane solution of N-isopropyl-N '- (2-carbmethoxy) phenylsulphamide, which significantly reduces the yield and purity of N-isopropyl-2,1,3-benzothiadiazine. 4-one -2,2-dioxide. The final product prepared according to the invention does not need to be further purified from the point of view of application.

In the process of the invention, a solution of N-isopropyl-N '- (2-carbmethoxy) phenylsulfamide in 1,2-dichloroethane is prepared and azeotroped off. The residual water is disposed of 3 to 7 parts by weight, preferably 4 to 5 parts by weight, of phosphorus oxychloride per 1 part by weight of water present in the azeotropically dried solution of N-isopropyl-N '- (2-carbmethoxy) phenylleulfamide. The resulting intermediate is cyclized with 30% by weight of sodium methanolate, the sodium salt of N-isopropyl-2,1,3-benzothiadiazin-4-one 2,2-dioxide being extracted with water. The aqueous bentazone sodium solution is freed from methanol by distillation and N-isopropyl-2,1,3-benzothiadiazin-4-one 2,2-dioxide is precipitated from the distillation residue with dilute hydrochloric acid in a ratio of 1: 1 to pH 3. The precipitate formed is filtered off, washed with water and dried to constant weight. An aqueous sodium salt solution is used as a 40% by weight application. The N-isopropyl-2,1,3-benzothiadiazin-4-one 2,2-dioxide obtained in this way is sufficiently pure and does not need to be purified by special procedures, as is necessary in the preparation of bentazone without disposal of residual water with phosphorus oxychloride.

Further advantages are apparent from the exemplary embodiments.

Example 1

28.2 g of chlorosulfonic acid are added to a solution of 78.4 g of 2-methylpyridine in 260 g of 1,2-dichloroethane for 5 minutes at 20 ° C. After stirring for 30 minutes, the temperature was raised to 25 DEG C. and 30.4 g of anthranilic acid methyl ester in 40 g of 1,2-dichloroethane were added at this temperature. After 30 minutes, isopropylamine is added to the mixture while maintaining the temperature of the mixture at 15 to 20 ° C. After 30 minutes, the temperature of the mixture is raised to 60 DEG C. and 30.6 g of phosphorus oxychloride are added at this temperature. After raising the temperature to 84 ° C, the mixture was refluxed for 2 hours. After cooling, the reaction mixture is mixed with 300 g of water. Created

CS 270 629 B1 the two-phase system is divided. The lower phase is a solution of N-isopropyl-N '- (2-carbmethoxy) phenylsulfamide in dichloroethane, which is dried by azeotropic distillation (azeotrope dichloroethane-water).

Example 2

The solution of N-isopropyl-N '(2-carbmethoxy) phenylsulfamide prepared according to Example 1 was divided into two equal sections. To the first part was added 37.5 g of 30% by weight of sodium methanolate, and the mixture was stirred at 25 ° C for 1 hour and then at 60 ° C for 1 hour. After cooling, the sodium salt of N-isopropyl-2,1,3-benzotladiazin-4-one 2,2-dioxide was extracted twice with 150 g of water. Methanol was distilled off from the aqueous layer, and 3-isopropyl-2,1,3-benzothiadiazin-4-one-2,2-dioxide was precipitated from the distillation residue with dilute hydrochloric acid 1: 1 to pH 3. The precipitated yellowish precipitate was filtered off. washed with water and dried to constant weight TI. Yield of bentazone: 17.3 g, which contained 82.6% by weight. N-isopropyl-2,1,3-benzothiadiazin-4-one 2,2-dioxide. The second part of the solution of N-isopropyl-N ^, (2-carbmethoxy) phenylsulfamide was treated as the first part, only the residual water after azeotropic dewatering (0.12% by weight of H ₂ O) was disposed of with phosphorus oxychloride (0.8 g 4.4 parts by weight, phosphorus oxychloride per 1 mass, water length). Yield of product: 19.8 g, which contained 96.3% by weight. 3-isopropyl-2,1,3-benzothiadiazin-4-one 2,2-dioxide.

Example 3

1,2-dichloroethane solution of N-isopropyl-N ^/ (2--Carbomethoxy) -fenylsulfamidu was prepared according to Example 1 are divided into two equal dialy (water content by azeotropic dewatering was 0.14% wt.). 0.21 g of water was added to the first portion (water content of the solution is 0.28% by weight). The water in the reaction solution was disposed of 1.9 g of phosphorus oxychloride. The procedure was as in Example 2. Yield of product: 19.7 g, which contained 95.7% by weight. N-isopropyl-2,1,3-benzothiadiazin-4-one 2,2-dioxide. 0.42 g of water was added to the second portion (water content of the solution is 0.42% by weight). The water in the reaction solution was disposed of 2.8 g of phosphorus oxychloride, corresponding to 4.4 parts by weight of water. The procedure was as in Example 2. Yield of product: 19.6 g, which contained 93.6% by weight. N-isopropyl-2,1,3-benzothiadiazin-4-one 2,2-dioxide.

Claims (1)

The two-phase system is split. Bottom phase A solution of N-isopropyl-N '- (2-carbomethoxy) phenylsulfamide in dichloroethane is dried by azeotropic distillation (dichloroethane-water azeotrope). Example 2 A solution of the N-isopropyl-N '(2-carbomethoxy) phenylsulfamide prepared according to Example 1 was divided into two equal lengths. To the first part was added 37.5 g of 30 wt. methanolic sodium hydroxide and the mixture was stirred at 25 ° C for 1 hour and then at 60 ° C for 1 hour. After cooling, the sodium salt of N-isopropyl-2,1,3-benzothiadiazin-4-one 2,2-dioxide was extracted twice with 150 g of water. Methanol was distilled off from the aqueous layer and 3-isopropyl-2,1,3-benzothiadiazin-4-one-2,2-dioxide was precipitated from the de-distillation residue with dilute hydrochloric acid 1: 1 to pH 3. The precipitated yellowish precipitate was filtered off, washed with water and dried the perfect weight. Bentazone Yield: 17.3 g, which contained 82.6 wt. N-isopropyl-2,1,3-benzothiadiazin-4-one 2,2-dioxide. The second portion of the N-isopropyl-N '(2-carbomethoxy) phenylsulfamide solution was treated as the first part, only the residual water after azeotropic dewatering (0.12 wt% HgO) was destroyed with phosphorous oxychloride (0.8 g 4.4 parts by weight oxychloride) phosphorous per 1 part by weight of water). Yield: 19.8 g, 96.3 wt. 3-isopropyl-2,1,3-benzothiadiazin-4-one 2,2-dioxide. Example 3 A 1,2-dichloroethane solution of N-isopropyl-N '(2-carbomethoxy) phenylsulfamide was prepared according to Example 1. It was divided into two equal volumes (water content after azeotropic dewatering was 0.14% w / w). 0.21 g of water was added to the first portion (the water content of the solution was 0.28 wt%). Water in the reaction solution was disposed of with 1.9 g of phosphorous oxychloride. The procedure was as in Example 2. Yield: 19.7 g, which was 95.7% by weight. N-isopropyl-2,1,3-benzothiadiazin-4-one 2,2-dioxide. 0.42 g of water was added to the second part (water content of the solution was 0.42% by weight). Water in the reaction solution was dispensed with 2.8 g of phosphorus oxychloride, corresponding to 4.4 wt. part per 1 wt. A portion of water was carried out as in Example 2. Yield: 19.6 g, which contained 93.6 wt. N-isopropyl-2,1,3-benzothiadiazin-4-one 2,2-dioxide. DESCRIPTION OF THE INVENTION A process for producing N-isopropyl-1,1,3-benzothiadiazin-4-one-2,2-dioxide from N-isopropyl-N '(2-carbomethoxy) phenylsulfamide by feeding sodium methanolate, characterized in that the dichloroethane solution of N-isopropyl-N '- (2-carbomethoxy) phenylsulfamide is phosphorus oxychloride in an amount of 3 to 7, preferably 4 to 5 wt. parts of POCl 3 per wt. part of the water present in the azsotropically dried dichloroethane solution of N-isopropyl-N '- (2-carbomethoxy) phenylsulfamide.