GB419458A - The manufacture of neutral, water-soluble derivatives of aminoarylarseno-stibio compounds - Google Patents

Abstract

Arylarseno-stibio compounds containing substituted amino groups are prepared by treating arylarseno-stibio compounds of the benzene series, which contain at least one amino group in each nucleus, with an alkylene oxide or derivative thereof and with formaldehydebisulphite or formaldehyde-sulphoxylate, simultaneously or consecutively, in the presence of a solvent. Alternatively, the treatment with the alkylene oxide compound and with the formaldehyde compound may precede, or partly precede and partly follow, the formation of the arylarseno-stibio compound by interaction of an aminophenylarsine with an aminophenylstibine oxide or halide. All the steps are carried out substantially in the absence of oxygen. The products, which may be subsequently treated with more alkylene oxide, an neutral water-soluble compounds of therapeutic value. According to the examples, (1) 4-hydroxy-3-aminophenylarsine acetate is treated with glycide, the product reacted with 4-hydroxy-3-aminophenylstibine chloride in methyl alcohol, and the arseno-stibio compound then treated with formaldehyde-bisulphite to give 4-hydroxy-3 - dihydroxypropylamino - 4<1> - hydroxy - 3<1> - (formaldehyde - bisulphite - amino) - arseno - stibiobenzene; the use of ethylene oxide, propylene oxide and formaldehyde-sulphoxylate is referred to; (2) 4-carbamino-3-dihydroxypropylamino-phenylstibine oxide is prepared by treating 4 - carbamino - 3 - aminophenylstibine chloride with glycide in methyl alcohol and reacted with 4-hydroxy-3-aminophenylarsine acetate in methyl alcohol to give 4-hydroxy-3-amino - 4<1> - carbamino - 3<1> - dihydroxypropyl - amino-arsenostibiobenzene, which is then converted into its formaldehyde-bisulphite compound; (3) 4 : 4<1> - dihydroxy - 3 : 3<1> - diaminoarsenostibiobenzene, prepared by interaction of 4-hydroxy-3-aminophenylstibine chloride and 4-hydroxy-3-aminophenylarsine, is treated in aqueous solution first with glycide and then with formaldehyde and sodium bisulphite. The sample is prepared by treating 4-hydroxy-3-aminophenylarsine acetate with diethylaminopropylene oxide, reacting the product with m - amino - p-carbamidophenylstibine chloride, and treating the resulting arsenostibio compound with formaldehyde-bisulphite. The use of butylene oxide is mentioned. Specifications 178,824, 226,686, and 326,537, [all in Class 2 (iii)], are referred to. The Specification as open to inspection under Sect. 91 refers also to the use of glucosane and dimethylaminopropylene oxide as alkylene oxide derivatives, and to alkylene oxides containing a chain of 3 to 6 carbon atoms. It also states that hydroxypropylaminophenylstibine chloride and 4-aminophenylarsine may be used in the process of (2) above. This subject-matter does not appear in the Specification as accepted. 4-Carbamino-3-aminophenylstibine chloride is obtained by nitrating4-carbaminophenylstibinic acid and reducing the 3-nitro product with stannous chloride in the presence of aqueous hydrochloric acid.