Activation and transfer of oxygen—XI : Autoxidative behaviour of some N1,3,5-methylated tetrahydrolumazines and dihydroalloxazines

The autoxidation of N_1,3,5-methylated tetrahydrolumazines and dihydroalloxazines and the covalent hydration of the oxidized (6,7-dihydrolumazinium and alloxazinium) species are described. Autoxidation led to ring contractions in which either the original C₄^a- or C₈^a_(10^a)-atom became the spiro center. In covalent hydration of the N_1,3,5-methylated cationic species a bridge position was not appreciably attacked, in contrast with the N_1,3,8(10)-methylated series. Instead, the N₅-substituent was preferably attacked by HO^? to give N₅-hydroxymethyl transients decomposing into formaldehyde and N₅-dealkylated tetrahydrolumazines or dihydroalloxazines, respectively. 4^a-Hydroxy derivatives were neither found as final products in the autoxidation nor in the covalent hydration.The two types of ringcontraction suggest that in some peroxy intermediates both C_4^a and C_8^a(10^a) may be linked to oxygen. The ringcontractions and N₅-demethylation are conversions on the level of the pseudobase. They must be distinguished from two other new intramolecular nucleophilic rearrangements on peroxide level leading respectively to: (1) the conversion of the N₅-methyl into a N₅-formyl group, indicating that the peroxy group may migrate to the N₅-carbon; (2) a cleavage of the C₄C_4^a and N₃C₄ bonds with the formation of CO₂ and a 2-oxo-3-ureido-tetrahydropyrazine derivative showing that the peroxy group may also be linked to C₄ to give other types of endoperoxides or cyclic peresters (peroxylactones).Nonenzymic hydroxylation of phenylalanine by the use of 1,3,5,7,8-pentamethyl-5,10-dihydroalloxazine was studied and the results compared with those obtained from a N_1,3,10-methylated derivative.