Structural studies on bio-active compounds. Part 3. Re-examination of the hydrolysis of the antimalarial drug pyrimethamine and related derivatives and crystal structure of a hydrolysis product

Abstract

Hydrolysis of the diaminopyrimidine pyrimethamine and some of its 5-(3′-substituted)phenyl derivatives with 6M-hydrochloric acid, or deamination with nitrous acid, affords mixtures of isomeric aminopyrimidinones. The ratio of products is influenced by the nature of the substituent in the phenyl ring.

The mixture of aminopyrimidinones from the hydrolysis of pyrimethamine crystallised from 95 % ethanol as a hydrated equimolar duplex. Crystals exhibited monoclinic symmetry, space group P2¹/n, with unit cell dimensions a= 24.297(6), b= 7.917(2), c= 13.312(4)Å and β= 98.09(3)°. The two isomeric molecules are linked by three hydrogen bonds in the manner of a Watson-Crick cytosine–guanine base pair.