N-Hydroxyamide-Containing Heterocycles. Part 2. Synthesis and Iron(III) Complex-Forming Tendency of 1-Hydroxy-2(1H)-pyrimidinone and -pyrazinone

The reaction of N-(benzyloxy)urea with 1,1,3,3-tetraethoxypropane, 4,4-dimethoxy-2-butanone, and 2,4-pentanedione under acidic conditions gave the corresponding 1-benzyloxy-2(1H)-pyrimidinones (3 and 3′) in moderate yields. In contrast, the reaction of N-(benzyloxy)urea or N-methoxyurea with 1-phenyl-1,3-butanedione exclusively gave 3-alkoxyimino derivatives (4). 1-Benzyloxy-2(1H)-pyrazinones (9a and 9b) were synthesized via three steps starting from N-(t-butoxycarbonyl)glycine. The hydrogenation or treatment with 30% HBr in acetic acid of compounds 3c, 9a, and 9b afforded 1-hydroxy-4,6-dimethyl-2(1H)-pyrimidinone (HOPY), and 1-hydroxy- (HOPR-H), and 1-hydroxy-5,6-dimethyl-2(1H)-pyrazinone (HOPR-Me), respectively. They form 3 : 1 complexes of iron(III) with the N-hydroxyamide groups in the acidic region, but the stability constants of their iron(III) complexes are far below that of natural ferrioxamine B.