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 pyrimidines. In particular, the treatment with 6 M HCl usually yields exclusively 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-diaminopyrimidine systems unexpectedly afforded exclusively the 4-amino-2-oxopyrimidine isomer (3). In this paper, we present the experimental work and ab initio calculations carried out to understand this discrepancy. As a part of such study, eight compounds containing a 2,4-diaminopyrimidine moiety were calculated in gas phase and in aqueous solution, and some acid hydrolyses were reexamined. Results showed that the presence of an electron-donating nitrogen linked to C6 of the 2,4-diaminopyrimidine ring changes the preferred hydrolysis site to yield the 4-amino-2-oxopyrimidine isomer.
Teixidó
J
J
Grup d'Enginyeria Molecular, Institut Químic de Sarrià, Universitat Ramon Llull, Via Augusta 390, 08017 Barcelona, Spain. j.teixido@iqs.url.edu
Borrell
J I
JI
Colominas
C
C
Deupí
X
X
Matallana
J L
JL
Falcó
J L
JL
Martinez-Teipel
B
B
D055598:Chemical Phenomena; D002627:Chemistry, Physical; D005493:Folic Acid Antagonists / Q000138:chemical synthesis / Q000737:chemistry*; D006868:Hydrolysis; D007202:Indicators and Reagents; D011743:Pyrimidines / Q000138:chemical synthesis / Q000737:chemistry*; D013762:Tetrahydrofolate Dehydrogenase
D005493:Folic Acid Antagonists; D007202:Indicators and Reagents; D011743:Pyrimidines; C017205:2,4-diaminopyrimidine; D013762:Tetrahydrofolate Dehydrogenase