Rapid aromatic hydrogen exchange in the antimalarial primaquine.

Primaquine, an 8-aminoquinoline antimalarial, is shown to undergo unexpectedly rapid aromatic proton exchange with the medium. At a pH less than 4, the exchange of C-5 is so fast as to be unmeasurable by proton nmr methods. At a pH of 6-6.5 the half-time for exchange is 4 to 5 minutes. This unexpectedly high rate of exchange of a carbon-proton with medium may provide an important clue to the biological activity of primaquine.