Calixarene - History

History

Adolf von Baeyer pioneered the chemistry of calixarenes although he was unable to determine its structure and did not realise its potential (he was pursuing dyes). In 1872 he mixed benzaldehyde with pyrogallol and a strong acid and noted a red-brown resin with a marked viscosity increase. He also used resorcinol and formaldehyde which he had to prepare from iodoform himself because a commercial grade of formaldehyde at that time had not been realised yet. In 1894 the Lederer-Manasse hydroxyalkylation was invented as a synthetic tool for the preparation of hydroxylmethyl phenols, bringing calixarenes one step closer. In 1902 Leo Baekeland made phenol formaldehyde resins a commercial success under the trade name Bakelite. In these resins phenol and formaldehyde are exhaustively condensed with each other to form heavily cross-linked polymers. The first attempt to control the reaction was made by Alois Zinke and Erich Ziegler in 1942. They employed para substituted phenols which inhibits crosslinking and should result in a linear polymer with formaldehyde. So in 1944 p-tert-butyl phenol with formaldehyde and sodium hydroxide in linseed oil as a solvent produced for the first time a crystalline solid with a high melting point rather than a resin. In the same year another duo by the names of Niederl and Vogel did something similar with a para substituted resorcinol and they were the first to postulate a cyclic tetramer. In these days structure elucidation was limited to determination of molar mass by freezing-point depression and functional group analysis.

John Cornforth was in 1955 the first to realize the potential of calixarenes as a basket analogue to enzymes and repeated the work done by Zinke. He obtained a mixture of products and elicited the services of Dorothy Crowfoot Hodgkin for structure elucidation by X-ray crystallography but with limited success. First commercial success came to calixarenes in the nineteen fifties when the company Petrolite started a range of calixarene products as demulsifiers used in the oil industry.

The word calixarene was coined by C. David Gutsche in 1975 who was also interested in this type of compound as biomimetic, since the molecule resembled the calyx krater vases of ancient Greece. It was by then established that unmodified calixarenes exhibit extensive conformational mobility so that the basket was not much of a basket after all. Donald J. Cram fixed this shortcoming by inventing a way of immobilizing calixarenes. He was able to freeze in a conformation by so called lower rim functionalization, replacing the hydroxyl groups by larger substituents. The acetate calixarene fixates the molecule as a partial cone, whereas the carbonate ester yields the full cone.