2-Phenyl-4-quinolones와 Methyl Iodide의 친핵반응에 의한 유도체의 합성

Nucleophilic Reaction of 2-Phenyl-4-quinolones with Methyl Iodide and Preparation of Its Derivatives

We developed a convenient synthetic route to 3-alkylated 2-phenyl-4-quinolone derivatives (4a-h and 5a-c), which were expected to retain antitumor activity. A series of 2,3-dihydro-2-hydroxy-2-phenyl-4-quinolones (3a-h) was synthesized through dehydration, dealcoholation and hydration using acid-catalyzed one-pot reaction from anilines and ethyl benzoylacetates. 3-Methyl (or 3,3-dimethyl)-2-phenyl-4-quinolone derivatives 4 and 5 were synthesized from 3a-h through the methylation using methyl iodide. Formation of quinolone nucleus was undertaken with p-toluenesulfonic acid (p-TSA) at 90~110℃ in toluene for 3~7.5 hr over the Dean-Stark apparatus. The key intermediates in these preparations are β-ketoesters 2a-h, which can be readily obtained from the corresponding anilines 1a-e by reaction with ethyl bezoylacetates.