Conformational and Stereoelectronic Control in Ring-Transformations of cis-4,5-Dialkoxytetrahydropurine-2,6,8-triones

Article abstract of DOI:10.1002/jhet.5570340220

Divergent acid-catalysed ring-openings of 4,5-dimethoxytetrahydropurine-2,6,8-triones 2 at position 4, yielding 1-(5-methoxyhydantoin-5-carbonyl)ureas 4 (R⁷ = Me) or 5-methoxy-5-ureido-2,4,6-pyrimidinetriones 5 (R⁷ = H), can be rationalized by assuming a preference for one of two conformational isomers of the cis-fused system, associated with the N-substitution effects. Intramolecular transamidation 5→4 presumably occurs via a bicyclic acid aminal type intermediate 3, heretofore misassigned as the reaction product. A curious base-catalysed rearrangement was encountered with the 5 (R¹ = R³ = Me, R⁷ = H) cases, which afforded 5-methoxy-1,5-bis(methylaminocarbonyl)hydantoins 7. Remarkable stability of the conformationally rigid propellane type 4,5-ethylenedioxytetrahydropurine-2,6,8-triones 9 toward acids, shows that the mode of zing-opening at position 4 is controlled by powerful stereoelectronic factors. However, an alternative ring-opening at the 1,6-bond has occurred on heating aqueous solutions of 9a (R⁷ = H); the ensuing decarboxylative rearrangement leads to 1,3-dimethylallantoin (12) and its precursor, 1-(2-hydroxyethoxy)-2,4-dimethyl-3,7-dioxo-2,4,6,8-tetraazabicyclo[3.3.0] octane(11).