DE1793157B2 - Process for the preparation of 6-amino-1,3-disulfamylbenzene derivatives - Google Patents

Description

(ΙΓ)

with at least an approximately 10 molar excess of aqueous ammonia in a closed System at a temperature of about 100 to about 150 C for about 2 to about 10 hours heated.

30th

So far, various attempts have been made to produce 4-chloro-6-amino-l, 3-disulfamylbenzene, which is a valuable intermediate for the preparation of the diuretic benzthiazide (3-benzylthiomethyl-'o-chloro ^ -sulfamyl-l ^ -benzolhiadiazine-ll -dioxyd) and polythiazide, using 4-chloro-6-fluoro-1,3-disulfamylbenzene as the starting material. Aqueous ammonia was used at -78 to 30 ⁰ C, so little or no fluorine during the reaction was replaced. When using reflux temperatures and using the same starting material, only small traces of ^ chloro-o-amino-l ^ -disulfamylbenzene were obtained even after three days of reaction. Furthermore, the use of aqueous ammonia together with sodium hydroxide at moderately elevated temperatures, for example 55 ° C., did not give the desired 4-chloro-6-amino-1,3-disulfamylbenzene.

6-Amino-1,3-disulfamylbenzenes can now be obtained by the process according to the invention, which is explained in more detail in the claim Produce in high yield from the 6-fluoro-1,3-disulfamylbenzenes.

The upper limit of the amount of ammonia used is not critical. A preferred upper one The limit is about a 40 molar excess. In this way a connection such as 4 - chloro - 6 - fluoro - 1,3 - disulfamylbenzene. / u 4-chloro-6-amino-1,3-disulfamylbenzene in yields converted up to about 74%.

In the process according to the invention, the ammonolysis is preferably used in excess aqueous ammonia carried out, the amount of ammonia in the ammoniacal solution a Concentration of about 10 to about 29 percent by weight, based on the total weight of the solution, is equivalent to. In a typical process, the 6-fluoro-1,3-disulfamyl-

Benzene was placed in an autoclave and the aqueous ammonia solution was then added. The system is then heated to a temperature of approximately 100 to 150 ^° C., as a result of which a pressure of approximately 2.8 to 24.6 atmospheres is achieved. The desired end product, namely 6-amino-1,3-disulfamylbenzene, can then, for example, by treating the reaction mixture with an amount of acid sufficient to adjust the pH to about 6.3 to 6.5, and then adding a sufficient amount of water can be recovered to the resulting crystalline dispersion.

The 6-fluoro-1,3-disulfamylbenzene starting materials required for the reaction are either known compounds or they can be prepared from readily available starting materials by known processes without difficulty. For example, they can be prepared from the corresponding fluorobenzene _{compounds by treating each 1} V-tere only with an excess of the required amount of chlorosulfonic acid in the presence of thionyl chloride as a dehydrating agent and then treating the disulfonyl chloride compound obtained with either ammonia or concentrated ammonium hydroxide.

From the intermediate products various l, 2,4-benzothiadiazine-l, l-dioxyde, which are used as oral diuretic and / or hypotensive agents are suitable manufactured (see GB-PS 9 09 687 and US-PS 30 09 911 and 31 33 060).

The following examples serve to illustrate the invention.

example 1

A solution of 20 g (0.07 mol) of 4-chloro-6-fluor-1,3-disulfamylbenzene in 200 ecm aqueous ammonia (29%) was ^{heated in a high pressure autoclave for 5 hours at 120 1} C, whereby a pressure of 17.58 atm was created. The reaction mixture was then cooled to room temperature, whereby a residual pressure of 0.35 atm was obtained. The device was then depressurized. The resulting product (198 ecm) was a clear liquid with a pH of 11.3. A portion (50 ecm) of this solution was then adjusted to a pH of 6.35 with 60 ecm of concentrated hydrochloric acid, and a crystalline dispersion was obtained which was further diluted with 125 ecm of water. The diluted dispersion was then filtered and washed with cold water. The dried product (74% yield) was 4-chloro-6-amino-1,3-disulfamylbenzene with a melting point of 256-258 ° C.

Example 2

The procedure of Example 1 was repeated except that the reaction was carried out at 100 ° C. for 10 hours. The ammonia pressure achieved in this way in the closed system was 2.81 atmospheres. In the same manner, the reaction was further carried out for 2 hours at 15O ⁰ C with an ammonia pressure was reached by 24.61 atm. In both cases, the results, insofar as they relate to the conversion of 4-chloro-6-fluoro-1,3-disulfamylbenzene to the corresponding 6-amino compound, were essentially the same in terms of both yield and purity of the product as that of example 1.

Example 3

The procedure described in Example 1 was repeated with the difference that an aqueous 10% (w / w) ammoniacal solution

instead of the 29% previously used Solution. The ammonia pressure achieved in the closed system was 4.92 atm. yield and purity of the product obtained were comparable to the results of Example 1.

Claims (1)

Claim: 1793 2 Process for the preparation of 6-amino-1,3-disulfamylbenzene derivatives the formula in the A a hydrogen, chlorine or bromine atom, a nitro, the trifluoromethyl, a lower one Alkyl or lower alkoxy group means, characterized in that one 6-fluorine-1,3-disulfamy! Benzene of the formula