Oxidative transformations of some pyrimidine derivatives into oxazolidine derivatives

Abstract

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.