J. Teixido et al., Selective hydrolysis of 2,4-diaminopyrimidine systems: A theoretical and experimental insight into an old rule, J ORG CHEM, 66(1), 2001, pp. 192-199
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.