Patent GB-470462-A (GB)
Title: Process for the manufacture of derivatives of aminobenzene sulphonic acid amides
IPC: C07C311/37
Filed: 1936-02-11
Abstract: Aminobenzene-sulphonamides, which contain one amino group and either one sulphonamide group in the para-position thereto or two sulphonamide groups in any position, are converted into their alkylene-sulphonates, -sulphinates or -carboxylates by treatment with alkyl-sulphonic acids, -sulphinic acids or -carboxylic acids containing a reactive substituent, such as halogen or hydroxyl, in the alkyl residue.  Alkali metal formaldehyde-sulphoxylates, chloracetic acid and b -chlorethanesulphonic acid are suitable reactants, but the use of alkali metal formaldehyde-bisulphites is excluded.  The same products may also be prepared from derivatives of the above aminobenzene-sulphonamides wherein the amino group is substituted by an alkyl group containing a reactive substituent, or by an alkylcarboxylic acid ester, amide or nitrile group; in the former case the reactive substituent is replaced by the sulphonic acid group using a sulphite, and in the latter case the ester, amide or nitrile group is saponified. Another method of preparation consists in reacting with ammonia or amines upon a mono-aminobenzene containing an alkylene-sulphonic acid, -sulphinic acid or -carboxylic acid residue in the amino group and either a sulphonic acid ester or halide group in para-position thereto or two such groups anywhere in the nucleus. The products, which may contain further substituents, possess therapeutic properties.  According to the examples: (1) phenylglycine-4-sulphonamide is prepared by treating 4-aminobenzene-sulphonamide with monochloracetic acid, or by converting it into 4-sulphonamide-phenylaminoacetic acid ethyl ester by reacting with chloracetic acid ethyl ester in presence of chalk and then saponifying; the ester may be transformed by means of methyl-alcoholic ammonia into the 4-sulphonamide-phenylaminoacetic acid amide before saponifying; (2) 4-aminobenzene-sulphonamide and aminobenzene - 3 : 5 - bis - (sulphonic acid dimethylamide) are treated with sodium formaldehyde-sulphoxylate; (3) formaldehyde solution is added to aqueous sodium cyanide and heated with 4-aminobenzenesulphonic acid dimethylamide to give 4-sulphonic acid dimethylamide-phenylglycine; the same product is obtained by treating the acid potassium salt of phenylglycine-4-sulphonic acid with chlorsulphonic acid and reacting the resulting sulphonic acid chloride with dimethylamine; (4) sodium a  - (4 - dimethylaminosulphonyl - phenyl) - methylamido - b  - hydroxypropane-g -sulphonate is prepared by interaction of 4-monomethylaminobenzene-sulphonic acid dimethylamide and epichlorhydrin, followed by boiling with sodium bisulphite solution; the starting material is produced by treating acetyl-methylaniline with chlorsulphonic acid, reacting on the resulting 4-acetylmethylaminobenzene-sulphonic acid chloride with dimethylamine and splitting off the acetyl group.  Specifications 430,580, 443,486, and 459,342 are referred to.  The Provisional Specification also describes the use of formaldehyde-bisulphite for introducing an alkylene-sulphonic acid residue into the amino group and contains an example of the treatment of 4 - aminobenzene - sulphonamide with sodium formaldehyde-bisulphite.  Phenylglycine-4-sulphonic acid is prepared by the action of sodium cyanide and formaldehyde upon aminobenzene-4-sulphonic acid, saponification of the cyanmethyl compound formed with potassium hydroxide, and acidification.