GB475948A - Process for the manufacture of barbituric acid compounds - Google Patents

Abstract

5 : 5-Disubstituted barbituric acids, in which one of the substituents is an isopropyl or isobutyl group and the other is a crotyl group, are prepared by condensing crotyl-malonic acids or crotyl-cyanacetic acids containing an isopropyl or isobutyl substituent, or derivatives thereof such as halides, esters, amides, nitriles or amide acid esters, with urea or its derivatives, e.g. guanyl-urea, guanidine, thiourea, isourea ethers, dicyandiamide or acyl compounds of urea and its derivatives, the products formed being converted, if necessary, into the barbituric acid. Alternatively, the crotyl group is introduced into a 5-isopropyl or -isobutyl-barbituric acid or derivative thereof, or an isopropyl group is introduced into 5-crotyl-barbituric acid or a derivative, by reaction with the appropriate halide, and the product converted, if necessary, into the barbituric acid. The products, which possess therapeutic properties, may be transformed into their salts directly or by double decomposition. According to the examples: (1) crotyl-isobutyl-barbituric acid is prepared by condensing crotyl-isobutyl-malonic acid ethyl ester with urea, acetyl-urea, guanidine or guanyl-urea in alcoholic solution containing dissolved sodium; when using guanidine or guanyl-urea, a subsequent treatment with boiling dilute sulphuric acid is necessary; (2) isobutyl-barbituric acid in alcoholic caustic soda solution is treated with crotyl chloride or bromide, advantageously in the presence of copper or copper compounds as catalyst; the product may be converted by means of sodium ethylate into its sodium salt, from which the calcium salt is obtained by double decomposition; (3) isopropyl-barbituric acid is reacted in caustic soda solution with crotyl bromide; the resulting crotyl-isopropyl-barbituric acid may be converted into its sodium or calcium salts or into salts with ethylene diamine, diethylamine, diethylamino-ethanol or piperazine; (4) crotyl-isobutyl-malonic ester is heated with dicyandiamide in the presence of sodium dissolved in methyl alcohol and the product boiled with dilute sulphuric acid; (5) crotyl-isobutyl-malonic ester and thiourea are heated together in alcohol containing dissolved sodium and the resulting thiobarbituric acid treated with nitric acid; (6) crotyl-isobutyl-malonyl chloride is reacted with urea. Crotyl-malonic, -cyanacetic and -barbituric acids and their derivatives are prepared by reacting upon the respective compounds containing no crotyl group with crotyl bromide in the presence of an alkali metal alcoholate.