Metal-Free C-H/C-H Coupling of 2H-Imidazole 1-Oxides with Polyphenols toward Imidazole-Linked Polyphenolic Compounds

The methodology of nucleophilic substitution of hydrogen (S-N(H)) was successfully applied as a convenient synthetic tool to afford azaheterocyclic derivatives of phenols of various architectures. A series of 26 novel imidazole-linked polyphenolic compounds were first prepared in 72-95% yields through the direct metal-free C-H/C-H coupling of polyphenols with 2H-imidazole 1-oxides. Comprehensive studies on the reaction condition optimization, scope, and limitations enabled the development of a straightforward method toward novel bifunctional derivatives bearing both phenolic and imidazole scaffolds of particular interest in the design of challenging molecules for versatile applications in medicinal chemistry and materials science.

Automated summary

The study successfully utilized the methodology of nucleophilic substitution of hydrogen to synthesize azaheterocyclic derivatives of phenols of various architectures, resulting in the preparation of 26 novel imidazole-linked polyphenolic compounds. This straightforward method enables the development of novel bifunctional derivatives with both phenolic and imidazole scaffolds, which are of particular interest for versatile applications in medicinal chemistry and materials science.