Deep-Cavity Calix[4]naphth[4]arene Macrocycles: Synthesis, Conformational Features, and Solid-State Structures

We recently introduced calix[<i>n</i>]naphth[<i>m</i>]arenes as a novel class of deep-cavity hybrid macrocycles constituted by phenol (n) and naphthalene (m) units. In this study, we report the synthesis, conformational analysis, spectroscopic properties, and solid-state structures of calix[4]naphth[4]arene (<b>C₄N₄</b>) and its permethylated analog (<b>C₄N₄-Me</b>), thereby expanding the calix[<i>n</i>]naphth[<i>m</i>]arene family. <b>C₄N₄</b> was synthesized through a 2 + 2 fragment coupling macrocyclization under acidic conditions, where the solvent played a crucial role in selectively forming the <b>C₄N₄</b> derivative. The X-ray structure of <b>C₄N₄</b> reveals a chair-like 1,2,3,4-alternate conformation characterized by two opposing 3/4-cone moieties stabilized by intramolecular hydrogen bonds. In contrast, the X-ray structure of <b>C₄N₄-Me</b> exhibits a 1,3,5,7-alternate conformation.