Purine-6,8-diones: A study of their ionisation and their methylation reactions

Purine-6,8-diones are divided by their physical properties into three classes: those of class (a) carry a hydrogen atom or a methyl group at position 1, and those of class (b) bear a 3-methyl substituent. The members of class (c), bearing both 1- and 3-methyl groups, exist either as betaines or, after protonation, as the conjugate acids, with the positive charge confined to the pyrimidine ring. Anions are formed predominantly by proton loss from position 9. Consistent with this, methylation of monoanions proceeds at position 9, except in the case of members of class (b). where alkylation at N-9 is sterically hindered by the 3-methyl substituent. Methylation of dianions follows in general the sequence of proton attachment, unless steric factors prevent this. Protonation and alkylation of neutral molecules proceeds predominantly in the pyrimidine ring. However in the case of 9-methyl derivatives, methylation at N-3 is sterically hindered.