An exhaustive computational mechanistic study of the Gould Jacobs type thermal cyclization using coupled clusters and DFT first principles methodologies

MALVACIO, IVANA; ELIZABETH L. MOYANO; D. MARIANO VERA

VILLA CARLOS PAZ - CORDOBA

Conferencia; 13-CLAFQO - 10a Conferencia Latinoamericana de Físico- Química Orgánica; 2015

The quinolone structure has been extensively used in a variety of pharmacologically active compounds as antibacterial1, anticancer2 and antimalarial3 among others.Since its first application in 1939, the Gould-Jacobs (G-J) reaction4 became one of the most common used strategies to synthesize quinolones. However, to the best of our knowledge, this complex multistep mechanism has never been study in-depth.Here we report a thorough computational mechanistic study of the G-J reaction performed using DFT and ab-initio (Coupled-Cluster) methods. The reaction between anilines (1) and diethylethoxymethylenmalonate (2) under microwave (MW) irradiation combined with Flash Vacuum Pyrolysis (FVP) was considered as a case study (Scheme 1).