Patent GB-482576-A (GB)
Title: Process for the manufacture of sulphonic acid amide compounds
IPC: C07C311/37
Filed: 1936-08-26
Abstract: 4 - Aminobenzene - sulphonamido - benzene-41-sulphonamide and its derivatives which contain sulphonic acid or carboxylic acid groups attached to the benzene nucleus located between the sulphonamide groups or in which the hydrogen atoms of the sulphonamide groups are replaced by substituents, are prepared by the following methods: (1) by converting into an amino group in the 41-position of a 4-(benzenesulphonamido)-benzene-sulphonamide a nitro, azo or hydrazo group by reduction, an acylamino or azo-methine group by hydrolysis, a halogen atom by reaction with ammonia or an amine, or a carboxylic acid amide or hydrazide group by Hofmann's or Curtius' method; (2) by treating 4-aminobenzene-sulphonic acid, or a derivative such as a halide, with 4-aminobenzene-sulphonamide or an appropriate derivative; (3) by reacting 4-aminobenzene-sulphonamide or suitable derivative thereof with a benzene-sulphonamide containing in the 4-position a halogen atom which has been rendered reactive by an adjacent nitro or carboxylic acid group, any nitro group being subsequently removed by consecutive steps of reduction, diazotization and reduction; (4) by treating 4-(41-aminobenzenesulphonamido)-benzene-sulphonic acid, or a derivative such as a halide, with ammonia or an amine.  In the second, third and fourth processes, the first reactant may be employed in the form of an acyl compound and the acyl group afterwards split off.  The products possess therapeutic properties. According to the examples, (1) 4-acetylaminobenzenesulphochloride is reacted with 4-aminobenzenesulphonamide and then hydrolyzed to give 4 - (41 - aminobenzene - sulphonamido) - benzene-sulphonamide; in the same way the sulphon-monomethylamide, -monoethylamide, -diethylamide, -dimethylamide, -butylamide, -oxyethylamide and -dioxyethylamide are prepared, also the sulphondimethylamide-3-carboxylic acid, sulphondiethylamide-3-carboxylic acid and sulphonamide-acetic acid, as well as 4 - (41 - dimethylaminobenzene - sulphonamido)-benzene-sulphonamide and -sulphondimethylamide; (2) 4-acetylaminobenzene-sulphochloride is reacted with 4-aminobenzene-sulphonic acid, the product converted into the sulphochloride by means of phosphorus oxy- and -penta-chlorides, treated with diethylamine, and finally hydrolyzed; (3) 4-nitrobenzenesulphochloride is combined with 4-aminobenzene-sulphonamide and the product reduced with hydrosulphite; (4) 3-nitro-4-chlorobenzene sulphondimethylamide, obtained from the sulphochloride and dimethylamine, is condensed with 4-acetylaminobenzene-sulphonamide and the nitro and acetyl groups then removed in the usual way; (5) azobenzene-4-sulphochloride is combined with 4-aminobenzene-sulphonamide and reduced with hydrosulphite; if desired the azo intermediate may first be converted into the hydrazo compound by reduction with sodium amalgam or zinc dust in aqueous alkali; the sulphon-monoethylamide and -dimethylamide products may similarly be prepared from the azo compounds; (6) 4-(41 - nitrobenzylideneamino) - benzenesulphochloride, obtained by treating 4-nitrobenzylidene-aniline with chlorsulphonic acid, is heated with 4-aminobenzene-sulphondimethylamide and the product hydrolyzed with hydrochloric acid to split off 4-nitrobenzaldehyde; (7) 4-(41-bromobenzenesulphonamido)-benzene-sulphonmethylamide, prepared by condensing 4-bromobenzene-sulphochloride with 4-aminobenzene-sulphonmethylamide, is heated with ammonia in an autoclave to produce the corresponding 41-amino compound; the iodo-and chlorostarting materials may also be used and the sulphonamide and sulphondimethylamide similarly prepared; by heating 4 - (41 - bromobenzenesulphonamido) - benzenesulphondimethylamide with dimethylamine the 41-dimethylamino compound is obtained; (8) toluene-sulphochloride is heated with 4-aminobenzene-sulphondimethylamide and after treatment with alkali permanganate solution to oxidize the methyl group to carboxyl, the product is converted into its acid chloride with phosphorus pentachloride, than by reaction with ammonia to the acid amide, and finally into the amino compound by means of potassium hypobromite; alternatively the acid chloride is reacted with hydrazine to form the hydrazide, which is then transformed into the amino compound by first converting it with nitrous acid into the azide, then into the methane by heating with alcohol, and finally by boiling with alkali solution. The diethylamine and diethanolamine salts of two of the products are mentioned. Specifications 442,135 and 470,461 are referred to.  The Provisional Specification also refers to the preparation of the products by reducing a 4 - (benzenesulphonamido) - benzene-sulphonamide containing a 41-nitroso group or by reacting such a sulphonamide containing a 41-hydroxy group with ammonia or an amine.  The starting materials for the first method are prepared as follows: (1) the 41-nitro compounds by reacting upon 4-aminobenzenesulphonamides with 4-nitrobenzene-sulphochloride; the 41-azo compounds by reacting upon 4-amino-benzene-sulphonamides with azobenzene-4-sulphochloride, obtainable from the sulphonic acid with phosphorus pentachloride; the 41-hydrazo compounds by mild reduction of the azo compounds; the 41-acylamino, -azomethine and -halogen compounds by reacting upon 4-aminobenzene-sulphonamides with the corresponding derivatives of benzenesulphochloride; the 41-carboxylic acid amides and hydrazides by reacting with ammonia and hydrazine respectively upon the oxidation products of 4-(41-methylbenzenesulphonamido)-benzene-sulphonamides after treatment with phosphorus pentachloride, the said 41-methyl compounds being prepared by reacting 4-methylbenzene-sulphochloride with 4-aminobenzene-sulphonamides.