Cyclodehydration of 5-pyrimidines. Synthesis and Characterization of Novel Mesoionic Imidazopyrimidin-3-ones

Article abstract of DOI:10.1021/jo00088a031

The cyclodehydration of 5-(carboxymethyl)amino-substituted pyrimidines using acid anhydrides has provided a general synthesis of novel mesoionic imidazo<1,2-c>pyrimidin-3-one compounds.The complete structural characterization and chemical reactivity studies of these compounds, including X-ray crystal structures for compounds 9c and 16a, were determined.Compounds lacking a blocking group at N-1 were found to undergo clean alkylation at this position, under basic reaction conditions, with substituted alkyl chlorides.Imidazo<1,2-c>pyrimidin-3-ones having a benzyl group at N-1 were found to undergo substitution reactions on the pyrimidine ring in the presence of basic nucleophiles.Thus, replacement of a 5-methylthio over a 7-chloro substituent was favored, whereas the 7-chloro group was substituted in compounds where a 5-amino substituent was present.Exposure of imidazo<1,2-c>pyrimidin-3-ones to aqueous acid results in the ring opening of the five-membered ring with subsequent loss of carbon dioxide or trifluoroacetate in an overall net reversion of the cyclodehydration reaction.Examination of the X-ray structures obtained for compounds 9c and 16a indicated that the five-membered ring was not aromatic, but rather a combination of a ring-opened valence tautomer and a charge-delocalized resonance hydrid structure.