Patent GB-486421-A (GB)
Title: Process for the manufacture of sulphonic acid amide compounds
IPC: C07C311/37
Filed: 1936-08-29
Abstract: p-Aminobenzene-sulphonic acid arylamides which contain a carboxylic and/or sulphonic acid group in the aryl nucleus but are otherwise unsubstituted in the aromatic nuclei are prepared according to the following processes: (1) reacting p-aminobenzene-sulphonic acid, its ester or halide, with an aryl compound containing a primary or secondary amino group together with a carboxylic and/or sulphonic acid group; (2) treating p-aminobenzene-sulphonamide with a halogen-aryl compound containing a carboxylic and/or sulphonic acid group; (3) converting into an amino group a substituent present in the p-position of a benzene-sulphonic acid arylamide containing a carboxylic and/or sulphonic acid group in the aryl nucleus, the conversion being effected by reducing a nitro, azo or hydrazo group, hydrolyzing an azomethine group or replacing a halogen atom by treatment with ammonia or a primary or secondary amine; (4) introducing a carboxylic or sulphonic group into the unsubstituted aryl radicle of a p-aminobenzene-sulphonic acid arylamide, by sulphonation with sulphuric or chlorsulphonic acid, or by saponifying sulphonic ester or halide groups, or by saponifying carboxylic ester, amide or nitrile groups, or by transforming the lower oxidation stages corresponding to the carboxylic or sulphonic acids, i.e. mercapto compounds, sulphuric acid derivatives, methyl, methylol or aldehyde groups, by oxidation to the carboxylic or sulphonic acid stage.  The products, which may be substituted in the p-amino group, possess therapeutic properties.  According to the examples: (1) p-acetylaminobenzene-sulphonic acid chloride is condensed with 3- or 4-aminobenzoic acid and the product saponified to give 3- or 4-(p-aminobenzenesulphonamido)-benzoic acid; (2) p-acetylaminobenzene-sulphonic acid chloride is reacted with 3- or 4-aminobenzene-sulphonic acid or with 1-naphthylamine-4-sulphonic acid and the product saponified; (3) p-acetylaminobenzene-sulphonic acid chloride is condensed with 1-naphthylamine-3 : 6-disulphonic acid, 1-naphthylamine-3 : 8-disulphonic acid or aniline-3 : 5-disulphonic acid, followed in each case by saponification; (4 4-acetylaminobenzene-sulphonic acid amide is heated with 2-bromobenzoic acid in the presence of copper powder and the resulting 2 - (p-acetylaminobenzenesulphonamido)-benzoic acid then heated to split off the acetyl group; (5) 4-(p-nitrobenzenesulphonamido) - benzenesulphonic acid, prepared by interaction of 4-nitrobenzene-sulphonic acid chloride and 4 - aminobenzene - sulphonic acid, is reduced with iron and acetic acid to the p-amino compound; (6) 3-(p-aminobenzenesulphonamido)-benzoic acid is prepared by treating 4-acetylaminobenzene-sulphonic acid chloride with 3-aminobenzonitrile and heating the product with caustic soda; (7) azobenzene-4-sulphochloride is condensed with 4-aminobenzoic acid and the 4-(p-azobenzenesulphonamido) benzoic acid reduced with sodium hydrosulphite to form the p-amino compound; (8) 4 - (41 - nitrobenzylidene - amino) - benzenesulphonic acid chloride is reacted with 4-aminobenzoic acid and the product saponified with hydrochloric acid to 4-(p-aminobenzenesulphonamido) - benzoic acid; (9) 4 - (p-bromobenzenesulphonamido) - benzoic acid, prepared by treating p-bromobenzene-sulphochloride with 4-aminobenzoic acid, is heated in an autoclave with ammonia or dimethylamine yielding the p-amino and p-dimethylamino compounds respectively; the chloro- and iodo-starting materials may also be used; (10) 4 - (p - acetylaminobenzenesulphonamido)-benzene - sulphonic acid phenyl ester is saponified with caustic soda solution; (11) p-acetylaminobenzene-sulphonic acid anilide is treated with chlorsulphonic acid and the resulting 4-(p - acetylaminobenzenesulphonamido) - benzene-sulphonic acid chloride heated with hydrochloric acid to give 4-(p-aminobenzenesulphonamido) - benzene - sulphonic acid; (12, 13) 4 - acetylaminobenzene - sulphonic acid chloride is reacted with 4-aminobenzoic acid ethyl ester and the product saponified with caustic soda to yield 4-(p-aminobenzenesulphonamido)-benzoic acid; the same product is obtained by saponifying the reaction product of 4-acetylaminobenzene-sulphonic acid chloride and 4-aminobenzene-carboxylic acid amide; (14) 4 - acetylaminobenzene - sulphonic acid-p-toluidide is oxidized with potassium permanganate and the product saponified to give 4 - (p - aminobenzenesulphonamido) - benzoic acid; (15) 4-acetylaminobenzene-sulphonic acid chloride is condensed with 4-aminobenzyl alcohol and the product oxidized and saponified as in (15) to produce the same product; (16) the reaction product of 4-acetylaminobenzene-sulphonic acid chloride with 2-aminobenzaldehyde is oxidized with potassium permanganate or 2-(p-aminobenzenesulphonamido)-benzoic acid obtained by saponification; (17) 4-acetylaminobenzene-sulphochloride is reacted with 1 : 4-aminothiophenol and the 4-(p-acetylaminobenzenesulphonamido)-1-thiophenol then oxidized with permanganate and saponified to 4-(p-aminobenzenesulphonamido)-benzene-sulphonic acid. Specifications 20192/14, 278,037, [both in Class 2(iii)], 442,135, 458,417, 470,461, and 474,423 are referred to.  Benzene-sulphonic acid arylides containing a carboxylic and/or sulphonic acid group in the aryl nucleus and a nitro, azo, hydrazo, halogen or azomethine group in the p-position of the benzene nucleus are obtained by reacting upon aminoaryl-sulphonic or -carboxylic acids with p-nitro-, -azo-, -halogen- or -azomethinebenzene-sulphochlorides, and to produce the hydrazo compound, by mild reduction of the azo compound. p-Aminobenzene-sulphonic acid arylamides containing sulphonic acid ester groups, carboxylic acid ester and amide groups, nitrile, sulphonic acid, methyl, methylol or aldehyde groups in the aryl nucleus are prepared by reacting with p-acylaminobenzene sulphochloride upon aminoaryl compounds containing the specified groups, and removing the aryl group by saponification.  p - Arylaminobenzene - sulphonic acid arylides containing a sulphochloride group in the aryl nucleus are obtained by treating p-aryl aminobenzene-sulphonic acid arylides with chlorsulphonic acid 4 - (41 - Nitrobenzylidene - amino) - benzene-sulphonic acid chloride is prepared by treating 4-nitrobenzylidene-aniline with chlorsulphonic acid.  4 - (p - Acetylaminobenzene - sulphonamido)-benzene-sulphonic acid phenyl ester is obtained by treating 4-nitrobenzene-sulphochloride with phenol, reducing the resulting phenyl ester with iron borings and acetic acid, and reacting the 4-aminobenzene-sulphonic acid phenyl ester so formed with 4-acetylaminobenzene-sulphonic acid chloride.