Patent GB-1182694-A (GB)
Title: Benzenesulfonyl Ureas and process for their manufacture
IPC: C07C303/40
Filed: 1967-05-30
Abstract: 1,182,694. Benzenesulphonyl-ureas. FARBWERKE HOECHST A.G. 30 May, 1967 [28 May, 1966; 18 April, 1967], No. 24852/67. Heading C2C. Novel benzenesulphonyl-ureas (including salts thereof) of the general formula wherein R is alkyl or phenylalkyl radical or preferably hydrogen, R<SP>1</SP> represents (a) a cyclohexyl radical containing a methyl group and an alkoxy group containing 1 or 2 carbons, (b) a chlorocyclohexyl group, (c) a spiro-(5,5)-undecyl-(3) group, (d) an exo-tricyclo-(3,2,1,0<SP>2,4</SP>) octane group, (e) a 4-methylcyclohexenyl group or (f) a dimethyl- or 4,4-diethylcyclohexyl group; X represents (a) a phenyl radical carrying in any desired positions the substituents Z and Z<SP>1</SP> which may be identical or different in which Z is a hydrogen or halogen atom or an alkyl, alkenyl, alkoxy, alkenoxy, haloalkoxy, alkoxyalkoxy, phenylalkoxy, phenylalkyl, cycloalkoxy, phenyl, phenoxy, acyl, acyloxy, or a benzoyl radical, or a -CF 3 , -OH, -CN or -NO 2  group, Z<SP>1</SP> represents a hydrogen or halogen atom or an alkyl, alkoxy, alkoxyalkoxy or acyloxy radical or a hydroxyl group, (b) a naphthyl radical which may be mono- or di-substituted by a halogen atom or an alkyl or alkoxy radical or a hydroxyl group, (c) a tetrahydronaphthyl radical or an indanyl radical, (d) a thienyl radical which may be mono- or di-substituted by alkyl, phenylalkyl, alkoxy, alkoxyalkoxy, alkenoxy, phenylalkoxy and aryl radicals and halogen atoms or (e) a tetramethylene- or trimethylene-thienyl radical and Y represents a hydrocarbon chain of 1-3 carbon atoms and wherein the phenylene group may be substituted by one or more halogen, alkyl or alkoxy, are prepared utilizing standard methods. 1 - [4 - (# - [2 - Methoxy - 5 - chlorobenzamido]- ethyl) - benzenesulphonyl] - 3 - (4 - chlorocyclohexyl)-parabanic acid is prepared by the interaction of 4-chlorocyclohexyl-parabanic acid and the appropriately substituted benzene-sulphochloride. N - [4 - (# - [2 - Methoxy - 5 - chlorobenzamido] - ethyl) - benzenesulphonyl] - N<SP>1</SP> - (4, 4-dimethylcyclohexyl)-thiourea is obtained by reacting 4,4-dimethylcyclohexylisocyanate with the appropriately substituted benzenesulphonamide. Treatment of this thiourea with HgO/ MeOH yields the corresponding isourea methyl ether and N - [4 - (# - [2 - methoxy - 5 - chlorobenzamido] - ethyl) - benzenesulphonyl] - N<SP>1</SP> - 2- chlorocyclohexyl-isourea methyl ether is similarly prepared from the corresponding thiourea. N,N<SP>1</SP> - Bis - 4 - [# - (benzamido - ethyl) - benzenesulphonyl]-urea is obtained by reacting 4-(#- benzamidoethyl ) -benzenesulphonamide sodium with 4 - (# - benzamidoethyl) - benzenesulphonyl-carbamic acid methyl ester. 4,4-Dimethylcyclohexyl parabanic acid is prepared by the interaction of 4,4-dimethylcyclohexyl-urea and oxalyl chloride. Exo - tricyclo - [3,2,1,0<SP>2,4</SP>] - octane - 3 - antiisocyanate and 4 - methyl - #<SP>3</SP> - cyclohexenylisocyanate are prepared by heating the corresponding acid azides which are in turn prepared from the corresponding acids. 4,4 - Diethyl - cyclohexyl - isocyanate is obtained by reacting 4,4-diethyl-cyclohexylamine with phosgene. 4 - Methyl - 3 - methoxy - (or 3 - ethoxy)- cyclohexylamine (the 3-methoxy compound being isolated as the acetate) are obtained by hydrogenating the corresponding benzene compounds. 4 - Methyl - #<SP>3</SP> - cyclohexenylamine is prepared by treating 4-methyl-#<SP>3</SP>-cyclohexenyl-isocyanate with acetic acid. 4-Chloro-cyclohexylamine is obtained by the interaction of 4-aminocyclohexanol and PCl 5 . Pharmaceutical preparations having hypoglycaemic activity comprise the above novel compounds in admixture or conjunction with a carrier, preferably in a form adapted to oral administration, e.g. tablets.