engleski

Microwave-assisted synthesis of 2(1H)-quinolone vs conventional synthesis

Quinolones are an important class of molecules present as a structural motif in a number of biologically active natural products and synthetic drugs. Due to known activity as pharmacophore, quinolone moiety attracted considerable attention to medicinal and synthetic organic chemists. Our interest was primarly focused on the construction of N- substituted 4-methyl-2(1H)-quinolone as the key intermediate in the total synthesis of marinoaziridines. Marinoaziridines are the first aziridine-containing natural products isolated from Gram-negative bacteria from marine sediment.Their absolute configuration is so far unknown as well as their total synthesis. The synthesis of 2(1H)-quinolone derivatives starting from suitably protected aniline and ethyl acetoacetate is a two-step process based on the attack of the amine on the ester function, which is thermodynamically favored, and occurs when the reaction is carried out at 180°C. The second step involves cyclisation of acetoacetanilides under harsh acidic conditions. The quinolone derivative was prepared via conventional method based on the above reaction sequence in a low yield (8 %) within long reaction time (7 days), together with unwanted byproducts. In an effort to improve yield and purity of products, and also to reduce reaction time, the synthesis was carried out under microwave irradiation. Efforts were made to optimize reaction conditions (power, temperature, time) for the first step, and to test a range of additives for the second step of reaction. Obtained results opened up the possibility of using different protecting groups which are not stable under harsh acidic conditions.

microwave-assisted synthesis ; conventional synthesis ; quinolone

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