Reactivities of Oxalamidines (N,N-Oxalins)

In order to determine the reactivity characteristics of putative oxalamidine metabolites (monoamidines of oxalic acid or N,N-oxalins), a series of cyclic and acyclic derivatives were synthesized and their reactivities examined. The results indicate that around neutral pH at 37°C oxalamidines are stable to hydrolysis or attack by nucleophiles typical of those that would be encountered physiologically. Also, under such conditions metal ions do not appreciably catalyze their destruction. The results further indicate that oxalamidines are stable to acid conditions (at least to 1 M HCl) but that they are readily hydrolyzed under basic conditions to oxamate derivatives. Kinetic and product data for the base-catalyzed reaction can be analyzed in terms of a mechanism similar to that proposed earlier for the hydrolysis of other amidines. This involves reversible addition of hydroxide to the protonated amidine followed by rate determining loss of amine.