Activation and transfer of oxygen—XI : Autoxidative behaviour of some N 1,3,5-methylated tetrahydrolumazines and dihydroalloxazines

Abstract

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 C 4 a- or C 8 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 N 5-substituent was preferably attacked by HO − to give N 5-hydroxymethyl transients decomposing into formaldehyde and N 5-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 N 5-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 N 5-methyl into a N 5-formyl group, indicating that the peroxy group may migrate to the N 5-carbon; (2) a cleavage of the C 4C 4 a and N 3C 4 bonds with the formation of CO 2 and a 2-oxo-3-ureido-tetrahydropyrazine derivative showing that the peroxy group may also be linked to C 4 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.