Patent GB-791529-A (GB)
Title: New sulphonamides
Filed: 1955-08-08
Abstract: The invention comprises naphthalene sulphonamides wherein one benzene ring of the naphthalene nucleus bears as a substituent the group SOxR, wherein x stands for 1 or 2 and wherein R stands for an alkyl radical of not more than 6 carbon atoms or for a phenyl radical, which may optionally be substituted by halogen atoms, and wherein the same or the other benzene ring of the naphthalene nucleus bears as a substituent the group SO2NHR1, wherein R1 stands for hydrogen or for an alkyl radical of not more than 6 carbon atoms.  It comprises also processes for the manufacture of these compounds either by oxidizing corresponding compounds which bear in place of the -SOxR substituent a substituent -SOyR, wherein y stands for 0 or 1, or by reacting corresponding compounds which bear in place of the -SO2NHR1 substituent the substitutent -SO2X, wherein X stands for halogen, with a compound of the formula NH2R.  The oxidation reaction is suitably effected by treatment with hydrogen peroxide, chromium trioxide or potassium permanganate in a solvent or diluent such as acetic acid or aqueous acetic acid.  The reaction of the sulphonyl halide with an amine NH2R1 is suitably effected in a solvent or diluent such as water, aqueous acetone or a mixture of water and ether.  Either reaction may be assisted by the application of heat. Examples describe the preparation of the 4-ethylsulphonyl-, 5-ethylsulphonyl-, 4-methylsulphonyl-, 4-n-propylsulphonyl - 4 - p - chlorophenylsulphonyl and 4 - ethylsulphinyl-, naphthalene - 1 - sulphonamides and also the 1 - ethylsulphonyl - 7 - sulphonamide, 2 - methylsulphonyl - 6 - sulphonamide, 4 - ethylsulphonyl - 1 - sulphonmethylamide, 4 - ethylsulphonyl - 1 - sulphonethylamide, 4 - ethylsulphonyl - 1 - sulphonisopropylamide and 4-ethylsulphonyl-1-sulphoniso butylamide derivatives of naphthalene. Starting materials.  Alkylthionaphthalene sulphonamides used as starting materials comprising methyl-, ethyl- and n-propyl-, thio-ethers of naphthalene sulphonamides and the appropriate ethyl thio-ethers of naphthalene sulphon methyl-, ethyl-, isopropyl- and isobutyl-, amides are made by diazotizing an aminonaphthalene sulphonic acid, treating the resulting diazonium salt with potassium ethyl xanthate in the presence of sodium carbonate to give the sodium salt of a thionaphthalene sulphonic acid, e.g. 4-thionaphthalene-1-sulphonic acid, converting this to the appropriate alkylthionaphthalene sulphonic acid for example by treating with ethyl sulphate to give an ethylthionaphthalene sulphonic acid, heating with a mixture of PCl5 and POCl3 to give a sulphonyl halide, and treating this with ammonia or an amine NH2R1 to give the desired alkylthionaphthalene sulphonamide.  2 - Methylsulphonyl - 6 - aminonaphthalene is made by converting 6-acetylaminonaphthalene-2-sulphonic acid into its sulphonyl chloride, methylating the sulphinic acid derived from this with methyl sulphate and hydrolysing the 2-methylsulphonyl-6 - acetylaminonaphthalene.  2 - Methylsulphonylnaphthalene-6-sulphonyl chloride is made by diazotizing 2-methylsulphonyl-6-aminonaphthalene, treating the diazonium salt with potassium ethyl xanthate in the presence of sodium carbonate, heating with aqueous sodium hydroide, precipitating with aqueous acid and treating the solid product in suspension in benzene with chlorine.  4 - p - Chlorophenylthionaphthalene-1-sulphonamide is made by treating 4 - thionaphthalene - 1 - sulphonic acid with p-chloronitrobenzene in the presence of sodium hydroxide, treating the resulting sodium salt of 4-p-nitrophenylthionaphthalene - 1 - sulphonic acid with PCl5 and POCl3 followed by ammonia to give 4 - p - nitrophenylthionaphthalene - 1 - sulphonamide, reducing the p-nitro group, diazotizing the resulting amine and treating the diazonium salt with cuprous chloride.ALSO:Pharmaceutical compositions having anti-convulsant and diuretic properties comprise sulphonamides which are naphthalene compounds wherein the naphthalene nucleus bears as substituents a group SOxR, wherein x is 1 or 2 and R is an alkyl radical of up to 6 carbon atoms or a phenyl or halophenyl radical and a group SO2NHR1, wherein R1 is hydrogen or an alkyl group of up to 6 carbon atoms, together with one or more pharmaceutical excipients.  Suitable compositions include tablets or pills containing between 5 and 90 per cent of the active constituent mixed with a diluent such as calcium carbonate or lactose, a disintegrating agent such as maize starch, a lubricating agent such as stearic acid or magnesium stearate and a granulating or binding agent such as starch paste, gelatin or gun acacia and aqueous dispersions in which 0.5-50 per cent by weight of the active constituent is dispersed in an aqueous medium with pharmaceutical excipients, for example, a neutral hydrophilic colloid such as sodium carboxymethyl cellulose and a wetting agent such as a polyethyleneoxycetanol.  Specified active compounds include methyl-, ethyl-, propyl- and p-chlorophenyl-, sulphonyl-naphthalenesulphonamides and ethylsulphinyl-naphthalenesulphonamides and corresponding derivatives wherein the sulphonamido nitrogen atom is substituted by alkyl groups such as methyl, ethyl, isopropyl or isobutyl groups.  Examples describe compositions comprising 4-ethylsulphonylnaphthalene - 1 - sulphonamide, maize starch, and magnesium stearate, in tablet form and an aqueous dispersion containing 4-ethylsulphonylnaphthalene - 1 - sulphonamide, sodium carboxymethylcellulose, heptadecaethylene - oxycetanol, methyl - p - hydroxybenzoate and propyl p-hydroxybenzoate.