Patent GB-604259-A (GB)
Title: Manufacture of 4-aminobenzenesulphonyl-ureas
Filed: 1945-12-22
Abstract: 4 - Aminobenzene - sulphonyl ureas of the general formula <FORM:0604259/IV(b)/1> (in which Ar represents a substituted or unsubstituted phenyl group) are prepared by the following processes: (a) treating a benzene sulphonamide of the formula <FORM:0604259/IV(b)/2> (in which R represents a substituent convertible into an amino group and X represents hydrogen or a metal) with a benzyl derivative of the formula Y-CH2-Ar (in which Y is an isocyano group, an acid-azide group or an acid-halogenamide group), and subsequently converting R into an amino group; (b) treating a benzene sulphonamide as in (a) with a benzyl derivative of the general formula Z-CO-NH-CH2-Ar (in which Z is a halogen atom, an alkoxy or thioalkoxy group) and subsequently converting R into an amino group; (c) treating a benzene sulphonamide of formula <FORM:0604259/IV(b)/3> with a benzyl derivative of the formula Alkoxy -CO-NH-CH2-Ar; (d) treating a benzene sulphonamide of the formula <FORM:0604259/IV(b)/4> (in which R1 is an amino group or a substituent convertible into an amino group) with a benzyl derivative of the formula NH2-CO-NH-CH2 -Ar and, when necessary, subsequently converting the convertible group into an amino group; (e) treating a benzene sulphonyl halide with a benzylisourea-O-alkyl ether of the formula <FORM:0604259/IV(b)/5> NH2-C(O Alkyl)=N-CH2-Ar, hydrolysing the product and converting R into an amino group; (f) treating a benzene sulphonamide as in (a) with a benzyl isothiocyanate, exchanging the sulphur atom in the thiourea derivative for oxygen by means of a desulphurizing agent, e.g. an alcoholic solution of silver nitrate, and subsequently converting R into an amino group; (g) treating a benzene sulphonamide of the formula <FORM:0604259/IV(b)/6> with a benzylamine and subsequently converting the R into an amino group; (h) treating a benzene sulphonamide of the formula <FORM:0604259/IV(b)/7> with a benzylamine and, when necessary, converting R1 into an amino group; (i) treating a benzene sulphonamide of the formula <FORM:0604259/IV(b)/8> with a benzylamine of the formula U-NH-CH2-Ar (in which U represents H or alkyl) or with a salt of such amine with an inorganic acid, and when necessary, converting R1 into an amino group, and (j) treating a benzene sulphonamide of the formula <FORM:0604259/IV(b)/9> with a benzylamine or with a salt of such amine with an inorganic acid, exchanging the sulphur atom in the product for oxygen by means of a desulphurizing agent, and subsequently converting the R into an amino group.  Salts of N-(4-aminobenzenesulphonyl)-N1-benzylurea are made by treating with a base, e.g. alkalis, alkali carbonates and bicarbonates, magnesium hydroxide, alkaline earth metal hydroxides, diethylamine, morpholine, aminoethanol and ethylene diamine.  In examples: (1) N-(4-aminobenzenesulphonyl) - N1 - benzylurea (and similarly N - (4 - aminobenzenesulphonyl) - N1 - (31,41 - dimethylbenzyl) - urea) is obtained from 4-acetylaminobenzenesulphonamide and benzyl isocyanate; (2), (3) and (4) the sodium, ethylenediamine and calcium salts are prepared from N - (4 - aminobenzenesulphonyl) - N1 - benzylurea; N - (4-aminobenzenesulphonyl) - N1 - benzylurea is made from (5) sodium 4-carbomethoxyaminobenzene sulphonamide and benzyl isocyanate; (6) sodium 4-nitrobenzene sulphonamide and benzyl isocyanate; (7) 4-nitrobenzene sulphonamide, benzylamine and phosgene; (8) potassium 4-aminobenzene sulphonamide and benzylaminocarbonic acid methyl ester; (9) 4-acetylaminobenzene sulphochloride and benzyl isourea-O-methyl ether methyl sulphate; (10) 4 - acetylaminobenzene sulphonamide and benzylurea; (11) 4-aminobenzene sulphonamide and benzylurea; (12) sodium 4-nitrobenzene sulphonamide, phenylacetic acid chloride and sodium azide; (13) sodium 4-acetylaminobenzene sulphonamide and N-bromophenylacetamide and (14) sodium 4-acetylamino benzene sulphonamide and benzyl isothiocyanate; (15) N-(4-aminobenzenesulphonyl)-N1-(31, 41-dimethylbenzyl)-urea is made from sodium 4-nitrobenzene sulphonamide and 3,4-dimethylbenzyl isocyanate; (16) N-(4-aminobenzenesulphonyl) - N1 - (41 - methylbenzyl) - urea is made from 4-acetylaminobenzene sulphonamide and 4-methylbenzyl isocyanate; N-(4-aminobenzenesulphonyl) - N1 - benzyl urea is made from (17) 4-nitrobenzene sulphochloride, silver cyanate and benzylamine; (18) 4-acetylaminobenzene sulphonamidocarbonic acid methyl ester and benzylamine; (19) 4-acetylaminobenzenesulphonyl urea and benzylamine; (20) 4-nitrobenzenesulphonyl urea and benzylamine; (21) 4-aminobenzenesulphonyl urea and benzylamine; (22) 4-acetylaminobenzenesulphonyl urea and benzyl-methylamine hydrochloride; (23) sodium 4-nitrobenzenesulphonyl urea and benzylamine, and (24) 4-acetylaminobenzenesulphonyl thiourea and benzylamine, using silver nitrate to desulphurize the intermediate product.  Specification 538,884 is referred to.  The Specification as open to inspection under Sect. 91 relates also to the preparation of compounds <FORM:0604259/IV(b)/100> in which R may be alkyl or cycloalkyl groups and includes also examples in which N-aminobenzenesulphonyl)-N1-benzylurea is made from (a) 4-nitrobenzene sulphenic acid chloride and benzylurea; (b) 4-nitrobenzene sulphenamide and benzyl isocyanate; and (c) N-(4-nitrobenzenesulphinyl)-urea and benzylamine; (d) N-(4-aminobenzenesulphonyl) - N1 - (a  - methylbenzyl) - urea is made from 4 - acetylamino - benzene sulphonamide and a -methylbenzyl isocyanate; (e) N-(4-aminobenzenesulphonyl)-N1-(a -ethylbenzyl)-urea is made from sodium 4-nitrobenzene sulphonamide and a -ethylbenzyl isocyanate; and (f) N-(4-aminobenzenesulphonyl)-N1-[a -(n-propyl)-31, 41-dimethylbenzyl]-urea is made from 4-nitrobenzene sulphonamide and a -(n-propyl)-3,4-dimethylbenzyl isocyanate. This subject-matter does not appear in the Specification as accepted.