Synthetic Studies Of 4-quinolone Derivatives

The 4-quinolone ring makes up the core structure of numerous natural products and synthetic compounds along with diverse biological properties, such as antibacterial, antitumor, antimalarial, anti-inflammatory, calpain inhibitory, anti-HIV-1 integrase. In addition, functionalized 4-quinolones are used as molecular fluorescent probes, ligands in coordination chemistry, and building blocks for the synthesis of other heterocyclic systems.The electrophilic substitution reaction of aromatic C-H bonds with intramolecular nitriles, known as Houben-Hoesch reaction, represents a classical organic transformation for the synthesis of benzene-fused cyclic ketones, such as 1-tetralone, thiochromone,9-acridinone. However, this reaction is usually restricted to a narrow scope of substrates and generally requires strong acidic conditions. The conditions of Houben-Hoesch reaction is optimized, therefore it can take place in a relatively mild condition. Through the condition experiments, the best condition of dry DMF and Tf2O(3equiv) at 80 ℃ was determined, considering the variate including temperature, solvent, as well as the kinds and dosage of anhydride.14 of the 4-quinolone derivatives were obtained using 18 of three different kind of the β-arylamino acrylonitriles,13 of the products are new compounds, all of the substrates and products were characterized by 1H-NMR and 13C-NMR, part of these products were characterized by IR and MS.In summary, a facile and efficient synthesis of 4-quinolone derivatives is developed via an intramolecular Houben-Hoesch reaction of β-arylamino acrylonitriles in the presence of Tf2O in DMF. The broad substrate scope, mild reaction conditions, and synthetic potential of the products make this novel protocol very attractive.