Patent GB-518903-A (GB)
Title: Process for the manufacture of sulphonic acid amide compounds
IPC: C07C311/37
Filed: 1938-09-08
Abstract: 518,903. Sulphonamides. I. G. FARBENINDUSTRIE AKT.-GES. Sept. 8, 1938, No. 26283. Convention date, Sept. 8, 1937. Sample furnished. [Class 2 (iii)] Processes are described for the preparation of benzenesulphonamide. derivatives containing (a) a sulphamic acid group in p-position to the sulphonamide group, or (b) a sulphamic acid group elsewhere in the molecule and another nitrogenous substituent, the nitrogen atom of which is linked to the nucleus, in p-position to the sulphonamide group. The compounds of type (b) may contain, as the nitrogenous substituent in p-position to the sulphonamide group, a nitro or amino group, an azomethine group such as a benzylideneamino group, a urethane group, or an amino group substituted by an alkyl, aralkyl or acyl group, which may be further substituted ; specified substituents which the amino group may carry are methyl, ethyl, butyl, dodecyl, benzyl, aminobenzyl, hydroxyethyl, methoxyethyl, acetyl, benzenesulphonyl, phenylacetyl, esterified carboxyalkyl, aminoalkyl, aminoaryl and aminoacyl groups such as aminoacetyl or amino - benzoyl groups. In the compounds of both types (a) and (b), the amino group of the sulphonamide group may Be primary, secondary or tertiary, and the substituents which may be linked to the nitrogen atom may be alkyl, aryl, aralkyl or cycloalkyl groups, such as methyl, ethyl, hydroxyethyl, aminoalkyl, phenyl, aminophenyl, aminobenzyl, aminonaphthyl, pyridine or quinoline radicles ; alternatively, the nitrogen atom of the sulphonamide group may form part of a hydrogenated heterocyclic ring, such as a pyrrolidyl or piperidyl ring. Further, in the compounds of both types (a) and (b), the benzene ring carrying the sulphonamide group may be further substituted, for example by alkyl, alkoxy or nitro groups or halogen. Sulphonamide-sulphamic acids of the types defined above are prepared by the action of halogensulphonic acids or their esters on benzenesulphonamides containing a primary amino group (a) in p-position to the sulphonamide group, or (b) in another position in the molecule, in which event another nitrogenous substituent, as indicated above, is present in p-position to the sulphonamide group ; in case (b), the primary amino group may be present in a substituent linked either to the nitrogen atom of the sulphonamide group or to the nitrogen atom in p-position to thesulphonamide group. The reaction is preferably effected in the presence of a tertiary amine, e.g., pyridine, quinoline or a dialkylaniline, or an inorganic acid-binding agent, a few being specified ; a solvent may also be present, and, in place of the halogensulphonic acids or esters, their addition products with tertiary amines may be used. In an alternative method of preparation, an amine containing a primary amino and a sulphamic acid group is condensed with a benzenesulphonic acid halide or ester substituted in p-position to the sulphonic acid ester or halide group by a nitrogenous substituent, the nitrogen atom of which is linked to the nucleus. Examples are given which sulphamic acids are prepared from 4- aminobenzenesulphonamide, 4-amino-2- methyl-5-methoxybenzenesulphonamide, 4- (41 - aminobenzenesulphonylamino) - benzenedimethylsulphonamide, 4-(4<1>-aminobenzylamino)- benzenesulphonamide, 4-nitrobenzenesul-. phonic acid p-aminoanilide, and 4:4<1>-bis-(4<11>- aminobenzenesulphonamido)-diphenyl (Specification 502,173), by reaction with chlorsulphonic acid in the presence of pyridine. An example is given also in which 3-aminoacetanilide is treated in pyridine with chlorsulphonic acid, and the product is boiled with causticsoda solution and then condensed with 4- nitrobenzenesulphochloride to yield 3-(4<1>-nitrobenzenesulphonamido)-benzenesulphamic acid ; 3 - (4<1> - acetylaminobenzenesulphonamido) - ben - zene sulphamic acid is similarly obtainable by using 4-acetylaminobenzenesulphochloride in place of 4-nitrobenzenesulphochloride. The salts of the products with alkali or alkalineearth metals, ammonia or amines form neutral aqueous solutions which may be used for injection. A sample has been furnished under Sect. 2 (5) of 4-(4<1>-carbethoxyaminobenzenesulphonylamino)-benzenesulphamic acid, prepared by treating 4-(4<1>-carbethoxyaminobenzenesulphonylamino)-aniline with chlorsulphonic acid in pyridine. 4 - - (4<1>- Carbethoxyaminobenzenesulphonylamino)-aniline, used in preparing the sample, is obtained by reducing (with iron and aqueous acetic acid) 4-(4<1>-carbethoxyaminobenzenesulphonylamino)-nitrobenzene, which is itself prepared from 4-nitraniline and 4-carbethoxyaminobenzenesulphochloride ; the latter is prepared from phenylurethane and chlorsul-. phonic acid.