DE1793157C3 - Process for the preparation of 6-amino-1,3-disulfamylbenzene derivatives - Google Patents

Description

H ₂ NO ₂ S-

F.
SO ₂ NH ₂

(II)

■ o

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-fluoro-1,3-disulfamylbenzene of the formula

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 4-chloro-6-amino-l, 3-disulfamylbenzene, the a valuable intermediate for the preparation of the diuretics benzothiazide (3-benzylthiomethylchloro-T-sulfamyl-1,2,4-benzothiadiazine-1,1 -dioxyd) and polythiazide, using 4-chloro-6-fluoro-1,3-disulfamylbenzene as a starting material. When aqueous ammonia was used at -78 to 30 ° C, little or no fluorine was produced replaced during implementation. When applying reflux temperatures and using the Even after three days of reaction, only slight traces of the same starting material were obtained ^ Chloro-ö-amino-l ^ -disulfamylbenzene. Also revealed the use of aqueous ammonia together with sodium hydroxide at moderately elevated temperatures, for example 55 ° C, not the desired ^ chloro-o-amino-l ^ -disulfamylbenzene.

According to the method according to the invention, which is explained in more detail in the claim, 6-amino-1,3-dishilfamylbenzenes can now be obtained 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 Grenz «is about a 40 molar excess. In this way a connection such as 4 - chloro - 6 - fluoro -1,3 - disulfamylbenzene, to ^ chloro-o-amino-l ^ -disulfamylbenzene in yields up to «about 74% converted.

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. In a typical procedure, this will be 6-fluoro-l, 3-disulfamylbenzene used as starting material placed in an autoclave and the aqueous Ammonia solution was then added. The system is then brought to a temperature of about 100 to Heated to 150 ° C, whereby a pressure of about 2.8 to? 46atü is achieved. The desired end product, namely o-amino-U-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 add a sufficient amount 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 obtained without difficulty by known methods from readily available Starting materials are produced. For example, they can be made from the corresponding fluorobenzene compounds produce by simply adding an excess of what is required Treated amount of chlorosulfonic acid in the presence of thionyl chloride as a dehydrating agent and treatment of the resulting disulfonyl chloride compound with either ammonia or concentrated Ammonium hydroxide connects.

From the intermediate products various l, 2,4-benzothiadiazine-l, l-dioxyde, which are used as oral diuretic and / or hypotonic agents are suitably prepared (cf. GB-PS 9 09 687 and US-PS 30 09 911 and 31 33060).

The following examples serve to illustrate the invention.

example 1

A solution of 20 g (0.07 mol) of 4-chloro-6-fluoro-1,3-disulfamylbenzol in 200 cc of aqueous ammonia (29%) was heated in a high pressure autoclave for 5 hours at 120 ⁰ 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 process of Example I was repeated with the difference 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 at 150 ° C. for 2 hours while the ammonia pressure reached 24.61 atm. In both cases the results, as far 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 was used instead of the 29% solution previously used. The ammonia pressure achieved in the closed system was 4.92 atmospheres. The yield and purity of the product obtained were comparable to the results of Example 1.

Claims (1)

Claim: Process for the preparation of 6-amino-1,3-disulfamylbeiizole derivatives the formula A.
H ₂ NO ₂ S NH ₂
SO ₂ NH ₂ (D