Metal-free Minisci C–H alkylation of hydrazones using aldehydes: an unexpected route to hydrazone-containing pyrimidine derivatives

Abstract

In this research, a novel method for synthesizing various heterocyclic derivatives via the Minisci radical substitution reaction has been presented. The Minisci reaction offers a very efficient and valuable approach for directly functionalizing heteroarenes with an electron-deficient group, allowing the formation of carbon–carbon bonds straightforwardly and efficiently. We have developed a metal-free, light-independent Minisci-type strategy for the direct C–H functionalization of pyrimidines, thereby facilitating the design of heteroaromatic derivatives containing hydrazone groups. The target derivatives were successfully synthesized in good yields using aromatic aldehydes as alkyl radical precursors. The reaction proceeds through a sequence of hydrogen atom abstraction (HAA) from the aldehyde, followed by decarbonylation under oxidative conditions using K₂S₂O₈ and trifluoroacetic acid (TFA). This method provides a practical and scalable approach to accessing structurally heterocyclic compounds of various classes.