2,408,066 Patented Sept. 24, 1946 [UNITED STATES PATENT OFFICE P-AMINO-IBENZENE-SULPHAMIDE ‘DERIVATIVES .Winfrid Hentrich, Rodleben, near 'Dessau-Ross ’lau, Anhalt, and Erik Schirm,'Dessau, Anhalt, Germany; vested‘ in the Alien Property Custo dian _ No Drawing. Application June‘ 3, 1939, Serial No. _ 277,300. In Germany May 5, 1938 _ 1 6 Claims. (01. zen-397.7) ; It hasv been found that technically valuable p amino-benzol-sulphimides of the general for 2 . . conversion of the groups contained in the mole cule, which allow of being conveyed into amino groups, is also performed to methods known in themselves. The .nitro-, azo- or azoxy-group respectively is converted into an‘ amino-group by reduction, and the acyl-amino-group by saponi are obtainable in causing the reaction of benzol ?cation. sulpho-halogenides, which in p-position contain ' . Y The’ sulphimides obtainable accordingv to the a substituent transformable into an amino group, present method are excelling by the fact that upon alkali-compounds of ' acid-amides of the 10 with alkalis, ammonia and numerous organic bases they givewater-soluble salts, the solutions general formula R,—X-‘—NI-Iz, or alkali-com pounds of benzol-sulphamides, which in p-posi of which react neutrally, which is of great im portance for their being ‘applied-particularly in amino group, upon acid-halogenides of the gen the pharmaceutical domain-eas remedies against eral formula R,—X-—Hal, and in forming then in 15 strepto- and staphylo-bacteria infections. It is the condensation-product the free ‘amino group true that similarly constituted sulphimides could already be produced, whereat the amino-group in a way known in itself. tion contain a substituent transformable into an In the aforementioned general formulas R means any acyclic or cyclic hydrocarbon residue of the amino-benzol-sulpho-residue was, how ever, not arranged in para-, but in meta-position. which may also contain hetero-atoms or hetero 20 Thosecompounds are of quite a different char atom groups such as oxygen, sulphur, nitrogen, acter and they did not prove e??cient as medical halogen, hydroXyl-, sulpho-, ether-, amino-, sub remedies andparticularly not against strepto stituted amino groups such as acylamino-, nitro-, ~ and ‘staph‘ylo-bacteria infections; ' azo-, azoxy-, ester-,Iacid-arnide groups and the Example 1 like; X means the groups S02 or CO, and Hal 25 means a halogen-atom and particularly a chloro _ 200 weight parts of, p-nitrobenzol-sulphochlo atom. By the groups ‘which according to well ride are dissolved in 1000*volume-parts of toluol. known methods are easily converted into an am Into this solution 193 weight-parts of p-toluol ino group and which, in the benzol-sulphohalo sulphamide-sodium are brought in the form of a genides or benzol-sulphamides respectively, ought 30 ?ne powder. Then the mixture is heated at the to be arranged in p-position to the sulpho-group, re?ux-cooler While stirring, until the toluol be we mean acyl-amine groups, the nitro-group, the gins to boil and at this temperature the mixture azo-group, the azoxy-group and the like. is kept for about 5 hours under permanent stir As to the acid-amides of the general formula ring. After cooling down the separated reaction R-—X—NH2 or, respectively, acid-halogenides of ' product is ?ltered oil’, then washed with a little the general formula R.—X—Hal there are to be considered for the present method e. g. the amount of alcohol and dissolved in a solution of 150 weight-parts of calcinated soda in 2500 weight-parts of water while warming. The hot solution is cleared by ?ltration and the ?ltrate is amides or halogenides respectively of the follow ing acids: acetic acid, butyric acid, lauric acid, stearic acid, methane-, ethane-, ethylene-, do 40 cooled in ice. After a several hours’ standing decane, hexadecane-, sulpho-acid, further the the sodium salt of the di-sulphimide abundantly benzoic acid, its homologues and substitution precipitating in the form of small crystal ?akes products, the phenyl-acetic acid, the phenoxy turning into a thickish crystal-mass, is sharply acetic acid, the naphthoic acid, the picolic and sucked off or pressed off, then covered with some nicotinic acid, the benzol-sulpho-acid, its homo logues and substitution products such as 2,5-di 45 ice-water and ?nally dried in the warmth. ory) of p-nitro-p'-methyl-dibenzol-sulphimide acid, the naphthaline-sulpho-acids etc. sodium. In working-up the mother-lye further amounts of the condensation-product may be The mixing of those acid-amides or -halogen ides respectively with the p-substituted benzol sulpho-chlorides or -amides respectively is per formed to well known methods either directly or in the presence of an indifferent diluent such as benzol, toluol, xylol, chloro-benzol, tetra-chlo We thus obtain 262 weight-parts (=77% of the the chloro-aniline-ll-sulpho-acid, ‘the benzyl-sulpho 50 gained. ‘ . 262 weight-parts of this nitro-compound are stirred, within half an hour at 60 to 65° 0., into a solution of 183 weight-parts of crystallized so dium-sulphide (NazS.9H2O) and 25 weight ro-hydrocarbon or the like. The subsequent 55 parts of sulphur in 1000 Weight-parts of water. 2,408,066 4 3 precipitated out, filtered in the cold and puri ?ed by dissolving and precipitating from diluted Then We stir for a further half an hour at 65°, whereupon we warm up to 80° in keeping this temperature for one hour. When the reaction alcohol. Example 3 is ?nished an exceeding of sodium-sulphide will still be traceable. The thus obtained solution 236 weight-parts of the sodium salt of the p is then cooled in ice. After a rather long stand acetyl-amino-benzene-sulphamide are suspend ing in the cold the meanwhile developed crystal mass is ?ltered 01f. ed in 150 volume-parts of toluene. To the sus From the ?ltrate a further amount of reduction-product is separating after an addition of common salt. pension 128 weight-parts of ethyl sulphonic acid chloride are added while stirring and the mix 10 ture is heated under re?ux for 5 hours. The re action mixture is cooled down and ?ltered, the residue is washed and dissolved in warm 5% soda For puri?cation the united precipitates are re crystallized from a little amount of water, where at the eventual yellow aspect can be eliminated lye. The solution is boiled until the acetyl group by an addition of a little amount of sodium hy is split off. After working up in the manner as drosulphite. The portions left dissolved are pre in Example 2 the p-amino-benzene-(ethyl) cipitated from the mother-lye by common salt. sulphimid of the formula Now the precipitates are dissolved in much water whereupon we acidify with muriatic acid and ?lter off the white precipitate, which we sub is obtained. sequently dissolve and precipitate from a large The sulphonamide derivatives obtained by the amount of boiling Water. After drying the sub prescribed processes having an alkyl sulphon res stance obtained forms a white micro-crystalline idue in the molecule such as p-amino-benzene powder with a flash-point of 231 to 232° C. (non methyl - sulphimid, p _ amino - benzene-ethyl corrected), which in a sodium-solution, while sulphimid, p - amino-benzene-propyl-sulphimid, forming a neutrally reacting sodium salt of the 25 p-amino-benzene-butyl-sulphimid and the like formula are especially valuable as they have a very good compatibility with the body. We claim: N9. ' 1. Compounds having the general formula is soluble. In the same way salts with organic 30 bases are soluble e. g. salts with tri-ethanol amine. Example 2 wherein R is an aliphatic radical and Z is se 236 Weight-parts of the sodium salt of the p 35 lected from the group consisting of hydrogen and alkalis, ammonia, and organic basic form acetamino-benzene-sulphamide are suspended in ing salts in combination with the rest of the 1000 volume-parts of xylol; then 133 weight molecule. parts of benZoyl-chloride are added, whereupon 2. An alkali metal salt of an Nl-alkylsulphonyl themixture is heated up at the re?ux-cooler for 3 "to 4 hours until the xylol begins to boil. The 40 sulphanilamide. 3. An Nl-alkylsulphonyl sulphanilamide. mixture is ?ltered after being cooled down, the 4. An Nl-butylsulphonyl sulphanilamide residue is Washed with a little amount of alco 5. An Nl-octylsulphonyl sulphanilamide. hol and taken in a warm exceeding 5%-sodium 6. An Nl-methylsulphonyl sulphanilamide. carbonate solution. The ?ltered solution is then boiled until the acetyl group is split off. By 45 acidifying with muriatic acid the obtained N (p' - amino - benzene-sulphonyl-)benzamide is W'INFRID HEN’I'RICH. ERIK SCHIRM.