Patent GB-1153272-A (GB)
Title: Benzenesulphonyl-Ureas and Process for their manufacture
IPC: C07D309/14
Filed: 1966-07-25
Abstract: 1,153,272. Benzenesulphonyl ureas. FARBWERKE HOECHST A.G. 25 July, 1966 [27 July, 1965], No. 33285/66. Heading C2C. Novel compounds of the formula (wherein R is C 1-4  alkyl or C 2-4  alkenyl; X is halogen, C 1-4  alkyl or C 1-4  alkoxy; and R<SP>1</SP> is cyclohexyl, methyl- or ethyl-cyclohexyl or endomethylene - (cyclohexyl or cyclohexenyl)- methyl) and salts thereof are prepared (1) by the action of amines NH 2 R<SP>1</SP> on the appropriately substituted benzenesulphonyl isocyanates, benzenesulphonyl carbamic or thiocarbamic acid esters, benzenesulphonyl carbamic acid halides or benzenesulphonyl ureas; or (2) by the action of R<SP>1</SP>-substituted isocyanates, carbamic acid esters, thiocarbamic acid esters, carbamic acid halides or ureas on appropriately substituted benzenesulphonamides; or (3) by reacting R<SP>1</SP>-substituted ureas, isourea or isothiourea ethers, or parabanic acids with appropriately substituted benzenesulphonyl halides and hydrolysing the products; or (4) by replacing the sulphur atom in appropriately substituted benzenesulphonyl-thioureas by an oxygen atom; or (5) by oxidizing appropriately substituted benzene-sulphinyl ureas or benzene-sulphenyl ureas; or (6) by acylating the corresponding #-aminoethyl compounds. Variations on the above methods are also referred to. N - {4 - [# - (2 - methoxy - 5 - methyl - benzamido) - ethyl] - benzenesulphonyl} - N<SP>1</SP> - (2,5- endomethylenecyclohexylmethyl) - isourea - methyl ether is prepared by reacting the corresponding thiourea (prepared from 2,5-endomethylenecyclohexylmethylisothiocyanate and the appropriately substituted benzene sulphonamide) with methanol in presence of mercury oxide at 50-55‹ C. The corresponding isothiourea methyl ether is prepared from the same starting materials in the presence of methyl iodide at reflux. N - {4 - [# - (2 - methoxy - 5 - chlorobenzamido) - ethyl] - benzenesulphonyl} - N<SP>1</SP>- (2,5 - endomethylene - cyclohexylmethyl) - thiourea is prepared as for the 5-methyl compound. N- {4 - [# - (2 - methoxy - 5 - chloro - benzamido)- ethyl] - benzenesulphonyl} - N<SP>1</SP> - cyclohexyl - isothiourea methyl ether is prepared by reacting the appropriately substituted benzenesulphonamide with CS 2  and KOH in DMF and water to give the corresponding benzenesulphonyl iminodithio carbonic acid potassium salt, reacting this with dimethyl sulphate in the presence of NaOH to give the dimethyl ester of the free acid, and reacting this with cyclohexylamine. N- {4-[#- (2- methoxy - 5 - chlorobenzamido) - ethyl] - benzenesulphonyl} - 3 - cyclohexyl - parabanic acid is prepared from the corresponding benzenesulphochloride and 1-cyclohexyl-parabanic acid. N - {4 - [# - (2 - methoxy - benzamido) - ethyl]- benzenesulphonyl] - N<SP>1</SP> - (4 - methylcyclohexyl)- urea is prepared by acylation of the corresponding #-aminoethyl compound with 2-methoxybenzoyl chloride; on bromination it gives the 5- bromo compound, a product of the invention. The benzenesulphonyl-ureas of the invention, which are stated to have a strong and longlasting hypoglycemic action, may be made up into pharmaceutical compositions for the treatment of diabetes mellitus with suitable carriers.