Synthesis of 3-cyano-2-pyridones from malononitrile : an honors thesis (HONRS 499)

Abstract

Substituted pyridones have multiple known uses in medicinal chemistry including topoisomerase inhibition in anticancer medicines. Cerpegin, a naturally occurring 2-pyridone, functions as an analgesic, anti-ulcer, tranquilizer, and anti-inflammatory. 2-Pyridones have also been associated with antitumor, antifungal, antibacterial, antiviral, and antithrombotic properties. Deri( atives of 2-pyridones are currently being researched as inhibitors of HIV-1 replication. Recently the condensation reaction of malononitrile with aldehydes and ketones has been examined. This condensation is extended to the uncatalyzed reaction of f3-diketones. This reaction requires two equivalents of malononitrile and produces 3-cyano-2-pyridones. An intermediate that provides information about possible mechanistic routes has also been isolated. The reaction pathway explored is ineffective in 13-diektones with large steric hindrances. Single products or multiple isomers in mixed ratios are obtained.