Patent GB-795606-A (GB)
Title: Sulphonyl urea derivatives
Filed: 1956-11-27
Abstract: The invention comprises sulphonyl ureas of the general formula: <FORM:0795606/IV (b)/1> wherein X and Y are hydrogen atoms or alkyl or alkoxy groups and R is a saturated open chain or cyclic hydrocarbon radical interrupted by at least one oxygen or sulphur atom, and the preparation of these compounds by the following methods: (1) reacting a benzene sulphonamide of the formula: <FORM:0795606/IV (b)/2> or an alkali metal salt thereof such as the sodium salt with a carbamoyl halide RNH.CO. Hal, where Hal is chlorine or bromine; (2) treating a benzene sulphonamide of the formula (I) with an ester of isocyanic acid of the formula O = C = NR or a substance which is converted into such an ester under the reaction conditions; (3) reacting the appropriate benzene sulphonyl isocyanate or a compound which is converted into a benzene sulphonyl isocyanate under the reaction conditions with an amine NH2R; (4) reacting the appropriate benzene sulphonyl halide with an alkyl ether of an isothiourea of the formula RHN.C(= NH).O alkyl and treating the resulting isourea derivative with an hydrohalic acid; (5) treating the corresponding benzene sulphonyl guanidine compound of the formula: <FORM:0795606/IV (b)/3> with hydrolysing agents such as alkali metal hydroxides to replace the imino group by oxygen; and (6) treating the corresponding benzene sulphonyl-thiourea with oxidizing agents or agents used for splitting off sulphur, to replace the sulphur atom by an oxygen atom.  Examples describe the preparation of benzene sulphonyl-, o-, m- and p-toluene sulphonyl-, p-isopropyl-benzene sulphonyl-, p-ethyl-benzene sulphonyl-, 3:4 - dimethoxybenzene sulphonyl -, 3 - methoxy - 4 - methylbenzene sulphonyl - and 3 : 4-dimethylbenzene sulphonyl-ureas of the above general formula in which R is chosen from 3-methoxypropyl -, 3 - ethoxypropyl -, 2 - isopropoxyethyl -, a  - tetrahydrofurfuryl-methyl -, 3 - methoxy - n - butyl -, 3 - methylmercapto - n - propyl -, 3 - n - butoxy - n - propyl -, 2 - ethoxyethyl -, 2 - methoxyethyl -, 2-isopropoxyethyl - and a  - tetrahydrofurfuryl-groups.  Specific products include the N1-(3-methoxy - n - propyl) -, N1 - (3 - methoxy - n - butyl) - and N1 - (a  - tetrahydrofuryl methyl)-N11 - (p - toluenesulphonyl) - ureas, the N1 - (3-methoxy - n - propyl) - and N1 - (3 - ethoxy - n - butyl) - (o - toluenesulphonyl) - ureas and N1 - (3 - methoxy - n - butyl) - N11 - (m - toluenesulphonyl)-urea. Starting materials.  Benzene sulphonyl isocyanates used as starting materials in method (3) above are prepared by reaction of a sulphonyl chloride with silver cyanate, or from the appropriate benzene sulphonamide and phosgene or by thermal decomposition of a sulphonyl derivative of carbamic acid.  Di-p-toluenesulphonyl urea and di-benzenesulphonyl urea are made by the action of phosgene on the corresponding sulphonamides.  p-Toluenesulphonyl ethyl thiourethane is made by the reaction of p-toluene sulphonamide with di-ethyl dithiocarbonate.  The isopropoxyethylamine salt of dip-toluenesulphonyl urea is prepared from its components. N-(p-toluenesulphonyl)-carbamic acid ethyl ester, N-(4-isopropyl benzenesulphonyl)-carbamic acid methyl ester, N-(p-ethyl benzene-sulphonyl) - carbamic acid ethyl ester, N - (3 : 4-dimethoxy - benzenesulphonyl) - carbamic acid methyl ester, N - (3 - methoxy - 4 - methyl - benzenesulphonyl) carbamic acid ethyl ester and N-(3 : 4 - dimethyl benzenesulphonyl) - carbamic acid methyl ester are made by reacting the corresponding sulphonamides with the methyl or ethyl esters of chloroformic or chlorocarbonic acid. 3-Methoxy-n-propylisourea methyl ether methyl sulphate is made by the action of dimethyl sulphate on 3-methoxy-n-propyl urea.