SU64799A1 - The method of obtaining sulfanilamide derivatives - Google Patents

Description

The industrial synthesis of sulfamide preparations is currently based on acetylsulfanyl chloride and, in part, on formylsulfanyl chloride as the essential intermediate products for the synthesis of any of these preparations. At the same time, acetanide and formanilide, the starting materials for the preparation of these intermediate products, require highly scarce acetic and formic acids to produce them (as a result of which they themselves are in short supply, limiting the production and increase in the production of sulfamide preparations.

To avoid the protective acylation of the amino group in the aniline molecule using scarce and expensive acetic and formic acids, the authors of the present invention propose a method for preparing sulfanilamide derivatives by reacting 4,4-carbanilide disulfonyl chloride with the corresponding amines. The resulting 4,4-carbanilsulfamide derivatives are further hydrolyzed under alkaline conditions.

The invention can be illustrated by the following examples:

Example I. Preparation of sulfanilamide and white streptocide.

In 422 g of 92% chlorofluoric acid is charged over. 1.5-2 hours while stirring 85 g of dry diphenylurea.

During the loading of diphenylurea, the temperature of the reaction mass is maintained in the range of 45-50 °. At the end of the loading, a two-hour exposure at 60 ° is given, then cooling to 20-25 °, and then the reaction mass is poured in a thin stream and with good stirring into ice water, which is added from time to time so that the temperature in the mass did not rise above + 3 °. The precipitated sulfochloride is filtered, it is well pressed from the mother liquor and, when stirred, is gradually introduced into 400 ml of 20% ammonia water. The temperature during amidation should not rise above 30 °, otherwise it is reduced by adding

ice After loading (the whole sulfochloride should be aged for 2 hours. The resulting carbanilide-disulfamide is filtered off, washed well (4-5 times) on the filter with water and then squeezed out of the solution well. 400 g of paste are obtained containing 115-120 g of dry matter .

A half-liter iron boiler is charged with a 40-50% sodium hydroxide solution containing 26 g; 100% NaOH (2 mol NaOPI per 1 mol of disulfamide), and then 400 g of the resulting disulfamide aqueous crust. The reaction mass is heated to 130 ° with stirring and maintained at this temperature for 4 hours.

The mass is then cooled to 95 ° and discharged. When the solution discharged from the apparatus is cooled to 15 ° (then a 30-minute exposure while stirring is given), technical sulfanilamide crystallizes out, which is then filtered from the mother liquor, washed with water (about 250 ml) until the filtrate color disappears and is well pressed on the filter.

Yield-79 g of dry technical sulfanilamide.

The resulting technical sulfanilamide paste is loaded and 700 ml of boiling water is added. After the product has dissolved, 8 g of activated carbon is added and the solution is heated for another 15 minutes and then filtered and cooled to 15 °. After one hour, the white streptocide that had cleared from the solution was filtered and washed until the reaction to the sulfate and chlorine was gone.

The yield of white streptocide (so pl. 167 °) -69 g (50% of theory).

Example 2. Getting red streptocide.

10 g of a 100% technical sulfanilamide (in the form of a paste) obtained by the method described in Example 1 is dissolved with

stirring in a 10-12% aqueous solution of hydrochloric acid (6.3 g of 100% PS1). Next, 40-50 g of ice is added to the solution, and sulphanoic acid hydrochloride amide is diazotized with 4.4 g of sodium nitrite (in the form of a 20% solution) at a temperature of 10-15 ° C.

The diazo solution obtained is added in minutes (with good stirring) to an 8-10% aqueous solution of metaphenylene diamine hydrochloride (6.5 g of 100% metaphenylene diamine). The temperature of the reaction mass in the azo process is maintained at 5-6 ° by adding ice. Simultaneously with the addition of diazo-solution, a 10-12% ammonia solution is added to the reaction mass in such a way that the reaction of the medium during the azo combining process (and after aging) remains slightly acidic on the Congo. At the end of the loading of the diazo solution, a 20 minute exposure is obtained while mixing, after which the mass is checked for acidity and the presence of excessive (optional) metaphenylene diamine.

Further, 160 ml of water is added to the mass, the mixture is heated for 10 to 15 minutes at 95-100 ° C to completely dissolve the technical red streptocide, and the hot solution is filtered out from undissolved impurities. The hot streptocide solution is then acidified with a chemically pure hydrochloric acid to distinctly; acidic to Congo, then cooled with vigorous stirring (external cooling). The precipitated red streptocide crystals are filtered off from the mother liquor and washed thoroughly with water until neutral to the Congo and obtain satisfactory results. In the absence of sulfate and chlorine ions.

The yield of pharmacopoeial red

Streptocide - 17.2 g (90% of theory). Melting point is 246 ° to 247 °.

Example 3. Getting sulfidine.

180 ml of a saturated solution of table salt, 18 g of dry table salt and 45 g of a 100% a-aminopyridine are heated to 40 °. Then, while stirring, 16 g of soda ash is loaded and after 10 minutes of aging, with vigorous stirring, 34.5 g of 100% 4.4-carbanishidisulfonyl chloride as an aqueous paste obtained by the method described in Example 1 is charged for 30 minutes. Paste pre-rinsed with a 10–12 dilution solution of soda ash (until alkaline for fenophthalein), and then with a saturated solution of common salt. After soaking for 40 minutes, 16 g of soda ash are charged again and after 30 minutes-34, 5; g. YuO-percent carbanilide sulfochloride. In this order, two more portions of the sulfochloride paste are charged. At the end of the loading of the whole sulfonyl chloride paste, it is allowed to stand at 40 ° for 1.5 hours, then 300 ml of water is added and after 30 minutes of stirring, the precipitated IB precipitate of carbanil or D4, 4, disulfamine pyridine is filtered off and washed well with water on the filter. The resultant 4,4-carbanilide disulfaminopyridine is hydrolyzed by heating at 130 ° with sodium hydroxide solution for four hours. The concentration of caustic soda B in the reaction mass is 8-10% (taking into account the water in the 4,4-carbanilide-sulfaminopyridine paste); the amount of caustic soda-4 mole per mole of carbaeyl disdaminopiridine. From the sodium salt solution (after hydrolysis), sulfidine is released in the usual way.

The yield of pharmacological sulphidine is 51% of the theory, based on the loaded α-aminopyridide.

Subject invention

A method of producing sulfanilamide derivatives, characterized in that 4,4-carbanilide disulfonyl chloride is acted with amines and the resulting derivatives of 4,4-carbanilide sulfamide are hydrolyzed in an alkaline medium with heating.