The first acid constant of calix[4]arenes

Abstract

A series of calix[4]arenes containing a single p-nitrophenol unit (or two p-nitrophenol units) have been synthesized by fragment condensation. Their first acid constant (pK_a1) has been determined in 2-methoxyethanol–water (9:1) by optical titration. Relative to the corresponding linear trimers with a p-nitrophenol in the middle, a decrease of pK_a1 by 2.1 units or more is observed, which can be explained entirely by intramolecular hydrogen bonds stabilising the monoanion. In this way electron-withdrawing p-substituents in the opposite phenolic unit lead to a further decrease in pK_a1, while a distortion of the cone conformation by m-methyl groups causes a slight increase. The structure of one calix[4]arene was further confirmed by single crystal X-ray analysis showing the molecule in the usual cone conformation.