Mechanistic Insights into the Formation of 1-Alkylidene/Arylidene-1,2,4-triazolinium Salts: A Combined NMR/Density Functional Theory Approach

In a recent report on the synthetic approach to the novel substance class of 1-alkylidene/arylidene-1,2,4-triazolinium salts, a reaction mechanism suggesting a regiose-lective outcome was proposed. This hypothesis was tested via a combined NMR and density functional theory (DFT) approach. To this end, three experiments with C-13-labeled carbonyl reactants were monitored in situ by solution-state NMR. In one experiment, an intermediate as described in the former mechanistic proposal was observed. However, incorporation of C-13 isotope labels into multiple sites of the heterocycle could not be reconciled with the "regioselective mechanism". It was found that an unproductive reaction pathway can lead to C-13 scrambling, along with metathetical carbonyl exchange. According to DFT calculations, the concurring reaction pathways are connected via a thermodynamically controlled cyclic 1,3-oxazetidine intermediate. The obtained insights were applied in a synthetic study including aliphatic ketones and para-substituted benzaldehydes. The mechanistic peculiarities set the potential synthetic scope of the novel reaction type.