Properties of the OH adducts of hydroxy-, methyl-, methoxy-, and amino-substituted pyrimidines: their dehydration reactions and end-product analysis

Abstract

Reactions of hydroxyl radicals (^•OH) with 2-amino-4-methyl pyrimidine (AMP), 2-amino-4,6-dimethyl pyrimidine (ADMP), 2-amino-4-methoxy-6-methyl pyrimidine (AMMP), 2-amino-4-hydroxy-6-methyl pyrimidine (AHMP), 4,6-dihydroxy-2-methyl pyrimidine (DHMP), 2,4-dimethyl-6-hydroxy pyrimidine (DMHP), 6-methyl uracil (MU), and 5,6-dimethyl uracil (DMU) have been studied by pulse radiolysis and steady-state radiolysis techniques at different pH values. The second-order rate constants of the reaction of ^•OH with these systems are of the order of (2-9) × 10⁹ dm³ mol^-1 s^-1 at near neutral pH. The difference in the spectral features of the intermediates at near neutral pH and at higher pH (10.4) obtained with these pyrimidines are attributed to the deprotonation of the OH adducts. The G(TMPD^•+) obtained at pH ~ 6, from the electron-transfer reactions of the oxidizing intermediates with the reductant, N,N,N',N'-tetramethyl-p-phenylenediamine (TMPD), are in the range (0.2-0.9) × 10^-7 mol J^-1 which constituted about 3-16% oxidizing radicals. These yields were highly enhanced at pH 10.5 in the case of AHMP, DHMP, DMU, and MU (G(TMPD^•+) = 3.8-5.5≅ 66-95% oxidizing radical). On the basis of these results, it is proposed that a nonoxidizing C(6)-ylC(5)OH radical adduct is initially formed at pH 6 which is responsible for the observed transient spectra. The high yield of TMPD^•+ at higher pH is explained in terms of a base-catalyzed conversion (via a dehydration reaction) of the initially formed C(6)-ylC(5)OH adduct (nonoxidizing) to C(5)-ylC(6)OH adduct which is oxidizing in nature. Among the selected pyrimidines, such a dehydration reaction was observed only with those having a keto (or hydroxy) group at the C(4) position of the pyrimidine ring. Qualitative analyses of the products resulting from the OH adducts of DHMP (at pH 4.5) and DMHP (at pH 6) were carried out using HPLC-ES-MS and a variety of products have been identified. Glycolic and dimeric products were observed as the major end-products. The product profiles of both DHMP and DMHP have shown that the precursors of the products are mainly the C(6)-ylC(5)OH and the H adduct radicals. The identified products are formed mainly by disproportionation and dimerization reactions of these radicals. The mechanistic aspects are discussed.