Gas-phase synthesis of 3-carboethoxy-quinolin-4-ones. A comprehensive computational mechanistic study to uncover the dark side of the Gould-Jacobs reaction

IVANA MALVACIO; E. LAURA MOYANO; D. M. A. VERA*

RSC Advances

The Royal Society of Chemistry (RSC)

Lugar: London; Año: 2016 vol. 6 p. 83973 - 83981

p { margin-bottom: 0.25cm; direction: ltr; color: rgb(0, 0, 0); line-height: 120%; }p.western { font-family: "Times New Roman",serif; font-size: 10pt; }p.cjk { font-family: "Times New Roman",serif; font-size: 10pt; }p.ctl { font-family: "Times New Roman",serif; font-size: 10pt; }Aset of 3-carboethoxy-quinolin-4-ones has been synthesized fromdiethyl 2‑((arylamino)methylene) malonates through aGould-Jacobs (G-J) cyclization using the flash vacuum pyrolysis (FVP)method. Mechanistic studies including calculations at firstprinciples DFT and Coupled Cluster (CCSD(T)) levels of theory, alongwith insightful experiments, have been gathered to shed light on thecomplex multi-step process to afford quinolones. The G-J cyclizationproceeded through a unimolecular process involving reactive speciesas iminoketenes, an azetinone and a quinolin-4(4aH)-oneintermediates. The reaction was rate limited by a proton shift stepin the pathway which leads to the final tautomeric product. In thegas phase pyrolysis of starting malonates, along with the expected3‑carboethoxy-quinolin-4-ones, 3-unsubstituted-quinolin-4-oneswere obtained, and the ratio between these products was stronglydependent on the nature of the arylamino group. In order to explainthe deethoxycarbonylation reaction, DFT and ab initiocalculations were also accomplished