Condensation reactions of calix[4]arenes with unprotected hydroxyamines, and their resulting water solubilities

In this report, we describe a convenient method to create neutrally charged, water soluble calix[4]arenes that contain hydroxyamides attached to their lower rims. Selective amidation reactions of a diacid calix[4]arene with several unprotected hydroxyamines was achieved using 2-ethoxy-1,2-dihydroquinoline as the coupling agent. The solubilities of the derivatized calix[4]arenes depended on the structure of the hydroxyamide, as well as, the number of hydroxyl groups. Molecular simulations of the derivatized compounds in water revealed that intramolecular H-bond formation is an important component of solubility. Calix[4]arenes containing 10 hydroxyl groups were as soluble in water as a calix[4]arene that contained two carboxylates.