KR840002429B1 - Process for preparing 3-chloro-1,2-benzoisothiazole-1,1-dioxide - Google Patents

Abstract

The title compds. (I) were prepd. by the reaction of II and PCl3 at 40-80≰C. Thus, 60 g 1,2-benzoisothiazoline-1,1-dioxide and 160 ml toluene were reacted with 55 g PCl3 and 1 ml dimethylformamide at 60≰C in a 500 ml flask followed by the steady introduction of chlorine gas into the flask. The product was crystallized with 200 ml toluene to give 62.5 g 3-chloro-1,2-benzoisothiazole-1,1-dioxide (95% yield).

Description

Method for preparing 3-chloro-1,2-benzoisothiazole-1,1-dioxide

The present invention relates to a process for the preparation of 3-chloro-1,2-bezoisothiazole-1,1-dioxide of formula (I).

The above-mentioned compound of formula (I) is not only known as a substance which is usefully used as an intermediate of a medicament for blast disease, but the preparation method of 1,2-benzoisothiazole-1,1-dioxide (cutting) of formula (II) It is known how to make a carine) as a starting material.

For example, Japanese Patent Publication No. 45-14302 discloses a method of reacting saccharin with phosphorus pentachloride in phosphorus oxychloride, which is difficult to control the reaction rate because phosphorus pentachloride is a solid. have. In other words, this method cannot keep the reaction system open due to the hydrogen chloride gas produced by the reaction product. Therefore, it is difficult to add a small amount of phosphorus pentachloride in a closed state. There is a problem that the reaction occurs too violent and the hygroscopicity is not high yield. However, phosphorus pentachloride has been widely used until recently because phosphorus pentachloride itself is less toxic and easier to handle.

Recently, a method of reacting thionyl chloride or phosgene with saccharin in the presence of dialkylformamide in dioxane solvent instead of phosphorus pentachloride has been developed. However, when using thionyl chloride, sulfite gas as a byproduct is corrosive. Because of its strong and toxic properties, the reactor had to be manufactured specially, and due to the amount of production cost associated with using expensive dioxane as a solvent, it was less useful as an industrial production method.

In addition, a method of reacting saccharin with phosgene in a hydrocarbon solvent is known, but in this case, the safety of handling due to the use of toxic phosgene appears to be a problem, and the reaction temperature is maintained at 80-150 ° C., in particular over 100 ° C. It should be.

It is an object of the present invention to provide a process for obtaining compounds of formula (I) in high yield in a simple and economical way.

The method of the present invention is characterized in that the saccharine of formula (II) is mixed with phosphorus trichloride in a hydrocarbon solvent and reacted with 40 g of chlorine gas at 40-80 ° C.

The process of the present invention is represented by the following scheme.

Phosphorus trichloride used in the method of the present invention is a liquid substance, and when the mixture is mixed with saccharin, the reaction is initiated by injecting chlorine gas without direct reaction. The reaction rate can be controlled while injecting the gas to achieve a quantitative reaction between saccharin and chlorine.

That is, phosphorus trichloride is a phosphorus compound like phosphorus pentachloride, but when it comes into contact with saccharin, no reaction occurs, so the entire amount required for the reaction can be put into a reaction vessel sealed with saccharin, so as in the case of phosphorus pentachloride There is no inconvenience in adding a small amount of solid material into the reactor. In addition, since the reaction is initiated according to the injection of chlorine gas, the reaction can be controlled by controlling the supply amount of chlorine gas, and the final product can be obtained with a high yield of 95% or more since a quantitative reaction occurs.

Moreover, according to the present invention, since a hydrocarbon solvent, which is inexpensive and easy to purchase, can be used as the reaction solvent, many economic advantages appear in industrial production.

As the hydrocarbon solvent used in the present invention, a benzene, toluene or the like is suitable, and in addition, a hydrocarbon solvent which does not affect the main reaction may be used.

In addition, according to the present invention sufficient reaction occurs even if the reaction temperature is maintained at 40-80 ℃, especially 50-70 ℃, which is necessary to maintain the reaction temperature compared to the reaction temperature 100 ℃ or more when using phosphorus pentachloride Production cost can be reduced compared to the use of phosphorus pentachloride, which leads to a reduction in fuel costs.

EXAMPLE

In a 500 ml flask equipped with a thermometer, a reflux cooler, and a gas injection tube, 60 g of 1,2-benzoisotaizoline-1,1-dioxide (saccharin) and 160 ml of toluene were added, 55 g of trichloride and 1 ml of dimethylformamide as a catalyst. Then, chlorine gas is slowly injected while maintaining the temperature of the reaction system at 60 ° C. After the reaction proceeded with hydrogen chloride gas, the mixture was left for about 2 hours, distilled off about 100ml of toluene and phosphorus oxychloride, cooled to room temperature, filtered, recrystallized from 200ml of toluene, and 3-chloro-1,2-benzoisothiane. 62.5 g of sol-1,1-dioxide was obtained. The product had a melting point of 141-144 ° C. and a yield of 95%.

Claims (1)

3-chloro-1 characterized in that 1,2-benzoisothiazoline-1,1-dioxide is mixed with phosphorus trichloride in a benzene hydrocarbon solvent and then reacted by injecting chlorine gas while maintaining the temperature at 40-80 ° C. A method for preparing, 2-benzoisothiazole-1,1-dioxide.