CYCLODEHYDRATION OF 5-[(CARBOXYMETHYL)AMINO]PYRIMIDINES - SYNTHESIS AND CHARACTERIZATION OF NOVEL MESOIONIC IMIDAZO[1,2-C]PYRIMIDIN-3-ONES

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 6-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 hybrid structure.