CH337545A - Process for the preparation of derivatives of aniline containing two CISO2 groups - Google Patents

Description

  

      Process for the preparation of derivatives of aniline containing two C1SO2 groups. The present invention provides a process for the preparation of derivatives of aniline of the formula
EMI0001.0004
    This process is characterized in that a compound of the formula
EMI0001.0005
    where R is hydrogen or a sulfonic acid group, R, hydrogen, halogen, an amino group or a lower alkyl or alkoxy radical and R = hydrogen or a lower alkyl radical,

    treated in the presence of an alkali halide with chlorosulphonic acid.



  The aminobenzene disulfonyl chlorides obtained in this way can be converted into the corresponding disulfamylanilines by treatment with ammonia. The substances obtained in this way are new compounds which primarily serve as intermediates for the production of pharmaceutically active substances, especially benzothiadiazine 1,1-dioxide compounds.

    The aminobenzene-disulfonyl chlorides are particularly suitable for the preparation of benzothiadiazine-1,1-dioxide compounds which have a substituent in the 3-position, while 3-unsubstituted benzothiadiazine-1,1- Dioxides are preferably formed from the corresponding disulfamylanilines.

   The disulfamylanilines also have diuretic and / or natriuretic effects.



  The process for the preparation of 5-chloro-aniline-2,4-disulphonyl chloride by treating m-chloro-aniline with chlorosulphonic acid in the presence of sodium chloride is of particular importance.



  The chlorosulfonation is, as said, carried out in the presence of an alkali metal halide, for example in the presence of sodium, potassium or lithium chloride. For all practical purposes, sodium chloride can be used, which is readily available, inexpensive and in the presence of which the reaction is relatively mild.

   However, since the reaction between these substances is somewhat violent, the aniline is preferably added dropwise to the chlorosulfonic acid with stirring and cooling. After the aniline has been added, the alkali metal chloride is best added in small portions in order to keep the evolution of hydrogen chloride at a moderate rate. The mixture is then conveniently heated to 100-200 ° C., preferably in an oil bath.



  <I> Example 1 </I> 64 g (0.5 mol) of m-chloro-aniline were added dropwise with stirring to 375 cm3 of chlorosulphonic acid, which was located in a 3-liter three-necked round-bottomed flask cooled in an ice bath. 350g sodium chloride were added in portions within 1-2 hours and the mixture was gradually heated to 150 ° C. in an oil bath. After heating to 150-160 ° C. for 3 hours, the flask was thoroughly cooled in an ice bath and its contents treated with 1 liter of cold water. The product was extracted with ether and the extract was washed with water and dried over sodium sulfate.

   After removing the ether on the steam bath, the remaining 5-chloro-aniline-2,4-disulfonyl chloride was recrystallized from benzene-hexane, melting point 130 to 132 C.



  <I> Example 2 </I> 15.2 g of o-chloroacetanilide were added in portions to 120 cm3 of chlorosulfonic acid at room temperature, whereupon 100 g of sodium chloride were added in portions over the course of 1 hour. The mixture was gradually heated to 150 ° C. over a period of 1/2 hour in an oil bath and then kept at this temperature for 2 hours.

   After vigorous cooling in an ice bath, the reaction mixture was treated with 500 cm ?, ice water, whereupon the product was taken up in ether, washed with water and dried over sodium sulfate. The remaining disulfonyl chloride was isolated by evaporating the ether on the steam bath.



  <I> Example 3 </I> 86 g (0.5 mol) of m-bromo-aniline were added dropwise within 1 hour to 375 cm 3 of chlorosulphonic acid, which was cooled in an ice bath. 350 g of sodium chloride were then added in portions over the course of 2 hours and the mixture was heated to 150 ° C. in an oil bath for 3 hours. After vigorous cooling in an ice bath, the reaction mixture was treated with 1 liter of ice water. The product was taken up in ether, washed with water and dried, and the ether was then removed on the steam bath.



  <I> Example 4 </I> By replacing the m-bromo-aniline used in example 3 with an equimolar amount of 5-amino-2-chlorobenzenesulfonic acid and otherwise proceeding essentially the same as in example 3, 4- Chloro-aniline-2,5-disulfonyl chloride. <I> Example S </I> 150 cm3 of chlorosulfonic acid were added dropwise to 24.6 g (0.2 mol) within 30 minutes with stirring

       m-anisidine in an ice bath. After the addition of chlorosulfonic acid was complete, 140 g of sodium chloride were added in portions over the course of one hour. The mixture was heated for 2 hours on the steam bath and then for 3 hours in an oil bath at 150-160 C, then cooled well in an ice bath and treated with 500 cm3 of ice water. The product was taken up in ether, washed with water, dried and the solvent evaporated on the steam bath.



  <I> Example 6 </I> By replacing the in-chloroaniline used in example 1 with an equimolar amount of m-fluoro aniline and otherwise proceeding essentially in the same way as described in example 1, 5-fluoro aniline 2,4-disulfonyl chloride.

 

Claims (1)

PATENT CLAIM Process for the preparation of derivatives of aniline of the formula EMI0002.0041 characterized in that one has a compound of the formula EMI0002.0042 where in the two formulas R is hydrogen or a sulfonic acid group, R1 is hydrogen, halogen, an amino group or a lower alkyl or alkoxy radical and R "is hydrogen or a lower alkyl radical, treated in the presence of an alkali halide with chlorosulfonic acid. SUBSTITUTE SHEET A method according to claim, characterized in that m-chloro-aniline is treated with chlorosulfonic acid in the presence of sodium chloride to form 5-chloro-aniline-2,4-disulfonyl chloride.