The synthesis of 6 4 [2-(dimethylamino)-4,5-dimethylphenyl]methylamino]-3-methyl-5-oxo-3H,5H-uracil (12b) has been carried out by peracid oxidation of the N5-quaternized 3-methyllumiflavi11, 10b (Scheme V), and the preparation of the 5-diazo-3H,5H-uracils (4a-c) and 5-oxo-3H,SH-uracil hydrazones (58-c) has been carried out as shown in Scheme IV. The structures of these compounds have been firmly established by 15N and 13C NMR as well as by other spectral methods. The 6-amino-5-oxo-3H,5H-uracil (12b) exists in aqueous solution below pH 9 mainly in its unhydrated form (unlike the analogous alloxane which once exposed to H 2 0 exists as a C5-covalent hydrate). In methanol 12b forms an isolable Cs-methanol adduct. Prolonged methanolysis and hydrolysis of 12b yields N,N',N',4,5-pentamethyl-o-phenylenediamine (IC), establishing that nucleophilic addition of the lyate species occurs at C6. The pH dependence of the hydrolysis of 12b has been investigated, and from the determined dependence of the first-order solvolysis constants upon acidity, reaction paths and mechanisms have been suggested. The hydrolytic properties of 12b have been compared to those of alloxane and flavins. Dithionite and hydrazine reduction of 12b yields the corresponding 6-[ [2-(dimethylamino)-4,5-dimethylphenyl] methylamino] -5-hydroxy-3-methyluracil (13b), which is easily reoxidized by O2 in CH3CN to 12b in a reaction first order in 13b. In aqueous solutions 13b undergoes an autocatalytic oxidation to 12b reminiscent of dihydroflavin and dialuric acid. The pH dependence of the reduction of 12b by hydrazine has been investigated. The reaction has been shown to involve the formation of a covalent adduct of hydrazine and 12b. Further, the adduct is not the hydrazone of 12b nor is it in equilibrium with 12b hydrazone (5c). The mechanism, which does not involve general or specific catalysis, is discussed. In CH3CN solvent the electrochemical reduction of 12b compares favorably to that of flavins. The electrochemical reduction of 12b occurs in two steps. The first one-electron transfer is quasi-reversible (Em, = 0.42 V NHE) while the second electron transfer appears chemically reversible but electrochemically nonreversible (Em2 approximates -1.1 V NHE). The IR spectral properties of the related 5-diazo-3H,5H-uracils (4a-c) and their reactivity are interpreted in terms of the most important canonical forms which contribute to their valence bond structures. It is concluded that the diazo carbonyl form (eq 14, A) is more important than the more charge delocalized diazonium enolate (eq 14, B) and that the oxadiazolo structure (V) can be disregarded. The 5-oxo-3H,5H-uracil 5-hydrazone ( 5 ) cannot be prepared by reaction of hydrazine with 12b due to hydrazine reduction of 12b to 13b. Once prepared 5c cannot be hydrolyzed to 12b without destruction of the pyrimidine ring. The hydrazones may be considered as isoelectronic and isosteric with corresponding resonance forms of proposed flavin-and pterin-derived carbonyl oxide intermediates in enzymatic monooxygena...
