Microwave-assisted one-pot synthesis of polycyclic 4-quinolone derivatives

G. C. MUSCIA; J. P. CARNEVALE; G. Y. BULDAIN; S. E. ASÍS

Rosario, Santa Fé

Workshop; 1 st Argentinean Workshop in Environmental Science.; 2009

Facultad de ciencias Bioquímicas y Farmacéuticas Universidad Nacional de Rosario

Acridine derivatives have a wide spectrum of biological activities as antibacterial, antimalarial, anticancer and mutagenic properties, principally connected with their ability to inhibit the enzymes acting on nucleic acids1. Furthermore, the condensation of anthranilic acid 1 and cyclohexanone 2 and IR-120 resin as catalyst in reflux toluene for 5-6 h gave the intermediate enamine derivative 3, which on cyclization in presence of phosphorous oxychloride afforded 9-chlorotetrahydroacridine. The nucleophilic substitution of the chloro group with different amines or phenols afforded the respective 9-substituted tetrahydroacridines, which were reported as antitubercular agents2. We have previously described the microwave-assisted synthesis of substituted quinolines employing the Friedländer reaction3 and among them were three acridine derivatives. In order to prepare new analogous compounds from anthranilic acid as starting material, a neat mixture of this and cyclohexanone was subjected to microwave irradiation at 400 W, for 1.5 minutes. Then the solid product 1,2,3,4-tetrahydroacridin-9-one 4 was obtained in good yield in a one-pot reaction instead of the enamine 3. Other cyclic ketone reagents such as cycloheptanone, dimedone and indanedione were reacted with anthranilic acid, so that the corresponding polycyclic 4-quinolone derivatives were prepared in short reaction times, good yields and eco-friendly conditions. All these products will be used as intermediates for the synthesis of potential antiparasitic and antineoplastic compounds.