Razi University

   in this study, the mechanism of a transition-metal-free cascade cyclization of N-aryl-N-(oxetan-3-yl)propiolamides with sodium azide was investigated using density functional theory (DFT) calculations. The reaction leads to the formation of hydroxymethyl-substituted triazole-fused piperazin-2-ones through a sequential process involving azide–alkyne cycloaddition followed by oxetane ring opening. The calculated reaction pathway indicates that the cascade is initiated by the formation of the azide–alkyne bond, whereas oxetane ring opening does not occur at the initial stage. The initially generated open-chain triazolide subsequently undergoes intramolecular cyclization to form a more stable triazolide intermediate. This intermediate then promotes the opening of the pendant oxetane ring through an intramolecular nucleophilic process, followed by proton transfer to produce the final neutral product. Alternative pathways involving initial oxetane ring opening were found to be energetically unfavorable. The calculations also provide insight into the reduced reactivity of the corresponding terminal-alkyne substrate. Rather than arising from an intrinsically high reaction barrier, its low reactivity is associated with the formation of a stable non-covalent complex involving the acidic terminal alkyne C–H bond and the NaN?/NaHCO? ion pair. Formation of this complex reduces the availability of the substrate for productive azide–alkyne bond formation. Overall, the computational results clarify the sequence of elementary steps involved in the cascade cyclization and provide a mechanistic explanation for the observed substrate-dependent reactivity, emphasizing the contribution of ion-pair interactions to the reaction pathway.