Collect. Czech. Chem. Commun. 1983, 48, 1212-1223

Oxidative transformations of some pyrimidine derivatives into oxazolidine derivatives

Jiří Křepelka, Vladimír Pouzar, Jiří Schlanger, Jiří Holubek, Jiří Körbl, Fedir Jančik and Rudolf Kotva

Research Institute for Pharmacy and Biochemistry, 130 60 Prague 3


The action of dilute hydrogen peroxide in aqueous alkaline solutions on compounds I-VI and XX produced derivatives of 2-iminooxazolidine-4-one, VII-XI and XXI. Their structures were demonstrated by spectral comparison with hydantoin derivatives XXII, XXIV and XXV, which were prepared from 2-aminoalkanedioic acids XXVIII, XXX and XXXI by reaction with potassium cyanate, followed by ring closure induced by a mineral acid. The structure of compound X was revealed by basic hydrolysis to 2-hydroxy-1,7-heptanedioic acid (XXVII) and by conversion of the latter, in an acid medium, into a derivative of oxazolidine-2,4-dione, XXIX. To elucidate the probable mechanism of the oxidative transformation, compound IV was converted by oxidation in an acid medium into the 5-hydroxy derivative XXXII. Exposure of the latter to an alkaline medium gave compound X. Bromination of acid IV with bromine, or with a mixture of potassium bromide and bromate in an acid solution, afforded the 5-bromo derivative XXXIV. Analogously, reaction of the acid IV with a mixture of hydrogen peroxide and hydrochloric acid gave the 5-chloro derivative XXXV. Boiling the compound XXXIV in aqueous sodium hydroxide led to the acid IV and a smaller amount of compound X. Reaction of the compound X with morpholine yielded the morpholine analogue XXXVI. In the screening for antineoplastic activity, compounds XXXII and XXXVI showed weak antitumors effects with some types of experimental tumors. Compound X was quite ineffective in the general pharmacological screening.