One-pot, Gram-Scale Synthesis of Calix[5]- and Calix[6]furan: Derivatization for Polyketone- and Isopyrazole-based Macrocycles with Conformational Analysis

A gram-scale synthesis of calix[5]- and calix[6]furan was achieved by a one-pot condensation of furan and acetone followed by stepwise separation of calix[n]furans (n=4-6) using size-selective precipitation procedures. Calix[n]furans were converted to cyclic polyketones and then to ethylene-bridged cyclic isopyrazoles. The conformational analysis of the cyclic furan, polyketone, and isopyrazole macrocycles was performed based on their single crystal structures, providing important structural insights for intermolecular interactions. The scalable synthetic procedures for larger calix[n]furans and their derivatives would contribute to further coordination and host-guest chemistry using their cavities. Gram-scale synthesis of calix[5]- and calix[6]furan was achieved through a one-pot process by improving the isolation process of the reaction mixture using size-selective precipitation techniques. The obtained calix[n]furans were transformed into cyclic polyketones and isopyrazole-containing macrocycles. Insights into host-guest interactions were obtained through systematic conformational analysis using single crystal structures. image