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

Abstract

A set of 3-carboethoxy-quinolin-4-ones were synthesized from diethyl 2-((arylamino)methylene) malonates through a Gould–Jacobs cyclization using flash vacuum pyrolysis (FVP). A detailed mechanistic study was done using DFT and Coupled Clusters models.

Thermal Ring‐Opening of Pyrazolo[3,4‐d][1,2,3]triazin‐4‐ones: An Experimental and Theoretical Study

“…Pyrazolotriazinone 4 could undergo nitrogen extrusion by a retro‐Diels–Alder reaction, as was proposed for the thermolysis of pyrrolotriazines 9 , or following ring‐opening, as was proposed for the photochemical reactions of benzotriazinones . Elimination of nitrogen from 4 could lead to the imidoylketene 6 or even an azetinone intermediate, which can coexist in equilibrium , . These intermediates could react with a nucleophile, in this case a second molecule of 4 or a better suited tautomer of it, to give the final product 5 .…”

“…Five main possibilities will be discussed and are labeled as paths A–E (Scheme ). The computational procedure was carried out at the CAM‐B3LYP/6‐311+G(d,p) level of theory, the efficacy of which was successfully proved in a related heterocyclic mechanistic study . The potential energy surface study was performed for the formation of compounds 5b (R = Ph) and 5c (R = p ‐MeO‐C 6 H 4 ), taken as representatives.…”

“…[17] Elimination of nitrogen from 4 could lead to the imidoylketene 6 or even an azetinone intermediate, which can coexist in equilibrium. [15,[18][19][20][21][22] These intermediates could react with a nucleophile, in this case a second molecule of 4 or a better suited tautomer of it, to give the final product 5. Similar nucleophilic reactions have previously been reported for benzoazetinones to give aminobenzamides and anthranilate esters.…”

“…The obtained stationary points were characterized by Hessian diagonalization and further harmonic frequency analyses to obtain zero‐point and thermal corrections for the energies, enthalpies, and free energies. In relevant cases, intrinsic reaction coordinate (IRC) simulations were started from the TS‐computed modes by using mass‐weighted coordinates and maximum step sizes ranging from 0.014 to 0.045 atomic units . A summary of IRC simulations for most cases are included in Figures S7–S16 in the Supporting Information, showing the electronic energies (relative to the TS energy) against the range of intrinsic reaction coordinate explored and the 3D structures of intermediates and TSs.…”

“…In relevant cases, intrinsic reaction coordinate (IRC) simulations were started from the TS-computed modes by using mass-weighted coordinates and maximum step sizes ranging from 0.014 to 0.045 atomic units. [22] A summary of IRC simulations for most cases are included in Figures S7-S16 in the Supporting Information, showing the electronic energies (relative to the TS energy) against the range of intrinsic reaction coordinate explored and the 3D structures of intermediates and TSs. All optimizations and frequency analyses were performed within the IEFPCM model for benzene, [32] the solvent used in the synthesis of 5b,c starting from 4b,c.…”