Selective hydrolysis of 2,4-diaminopyrimidine systems: A theoretical and experimental insight into an old rule

Hydrolysis of the amino groups in condensed 2,4-diaminopyrimidine systems ( 1) has been used as a common method for the synthesis of oxo-substituted py rimidines. In particular, the treatment with 6 M HCI usually yields exclusi vely the 2-amino-4-oxopyrimidine isomer (2). During our work, we found that the hydrolysis of the amino groups present in some condensed 2,4-diaminopy rimidine systems unexpectedly afforded exclusively the 4-amino-2-oxopyrimid ine isomer (3).In this paper, we present the experimental work; and ab init io calculations carried out to understand this discrepancy. As a part of su ch study, eight compounds containing a 2,4-diaminopyrimidine moiety were ca lculated in gas phase and in aqueous solution, and some acid hydrolyses wer e reexamined. Results showed that the presence of an electron-donating nitr ogen linked to C6 of the 2,4-diaminopyrimidine ring changes the preferred h ydrolysis site to yield the 4-amino-2-oxopyrimidine isomer.