Novel 2-Pyrazolin-5-One Derivative Through Unforeseen Orthoamide Intermediate: Mechanistic Insights On Isocyanide Based [4+1] Cycloaddition

This work relates a unique one-pot procedure to assembly novel 2-pyrazolin-5-one derivative functionalized through an isocyanide based formal [4+1] cycloaddition. A new, unexpected multicomponent reaction occurred when a pyrazolone was condensed with an aldehyde, an isocyanide, and water or alcohol components. Nine novel molecules with an embedded alkyl carboxamide group were obtained in moderate yield. Surprisingly, an unforeseen orthoamide intermediate was isolated and characterized, proving the plausible mechanism for the opened imidate obtained by formal [4+1] cycloaddition. This one-pot approach to pyrazolone derivatives functionalized with amides stands as a significant advance for preparing this class of molecules.