Studies in the flavin series. Part XVI. Alkylation and rearrangement reactions of dihydroalloxazines

Abstract

Alkylation of 5-acetyl-5,10-dihydro-1,3,7,8-tetramethylalloxazine (2) in dimethylformamide proceeded at the bridge position C(4a) or at N(10) to an extent dependent upon the alkylating agent. An increasing tendency for substitution at C(4a) in the order dimethyl sulphate < methyl iodide allyl bromide < benzyl bromide was found, and was interpreted as representing a trend from a hard to a soft electrophile. The relative reactivities indicated that C(4a) was a soft nucleophilic centre whereas N(10) was a hard centre. The bending of dihydro(iso)alloxazines about the N(5)–N(10) axis is considered to have an important influence on the reactivities at N(10) and C(4a). 5-Deacetylation resulted in migration of an allyl or benzyl substituent from N(10) to C(4a); the derivatives with a saturated alkyl group at N(10) did not show this migration.