Calixarene

A calixarene is a

Calixarenes are generally produced by condensation of two components: an electron-rich aromatic compound, classically a 4-substituted phenol, and an aldehyde, classically formaldehyde.[4]^[5]

• The scope for the aromatic component is broad diverse. The key attribute is susceptibility toward hydroxyalkylation. The related resorcinarenes and pyrogallolarenes are produced from resorcinol and pyrogallol, respectively.
• The aldehyde most often used is formaldehyde, while larger aldehydes, like acetaldehyde, are usually required in condensation reactions with resorcinol and pyrogallol to facilitate formation of the C_4v symmetric vase conformation. Additionally, substituted aldehydes and some heterocycles (e.g. furan) may be used to impart additional functional groups onto the pendent groups of resorcinarenes and pyrogallolarenes.^[6][7]

Calixarenes can be challenging to synthesize, producing instead complex mixtures of linear and cyclic oligomers. With finely tuned starting materials and reaction conditions, synthesis can also be surprisingly efficient. Calixarenes are sparingly soluble as parent compounds and have high melting points.^[8]

Structure

Calixarenes are characterised by a three-dimensional basket, cup or bucket shape. In calix[4]arenes the internal

.

Calix[4]arene with para-tert-butyl substituents	3D representation of a cone conformation

History

In 1872 Adolf von Baeyer mixed various aldehydes, including formaldehyde, with phenols in a strongly acidic solution. The resultant tars defied characterization; but represented the typical products of a phenol/formaldehyde polymerization. Leo Baekeland discovered that these tars could be cured into a brittle substance which he marketed as "Bakelite". This polymer was the first commercial synthetic plastic.

The success of Bakelite spurred scientific investigations into the chemistry of the phenol/formaldehyde reaction. One result was the discovery made in 1942 by Alois Zinke, that p-alkyl phenols and formaldehyde in a strongly basic solution yield mixtures containing cyclic tetramers. Concomitantly, Joseph Niederl and H. J. Vogel obtained similar cyclic tetramers from the acid-catalyzed reaction of resorcinol and aldehydes such as benzaldehyde. A number of years later, John Cornforth showed that the product from p-tert-butylphenol and formaldehyde is a mixture of the cyclic tetramer and another ambiguous cyclomer. His interest in these compounds was in the tuberculostatic properties of their oxyethylated derivatives.

In the early 1970s

Concomitant with Gutsche's work was that of the Hermann Kämmerer and Volker Böhmer. They developed methods for the stepwise synthesis of calixarenes. Chemists of University of Parma, Giovanni Andreetti, Rocco Ungaro and Andrea Pochini were the first to resolve X-ray crystallographic images of calixarenes. In the mid 1980s, other investigators joined the field of calixarene chemistry. It has become an important aspect of supramolecular chemistry and attracts the attention of hundreds of scientists around the world. The Niederl cyclic tetramers from resorcinol and aldehydes were studied in detail by Donald J. Cram, who called the derived compounds "cavitands" and "carcerands". An accurate and detailed history of the calixarenes along with extensive discussion of calixarene chemistry can be found in Gutsche's monograph.

Host guest interactions

Water soluble calixarenes, such as para-sulfontocalix[4]arene, have been examined for drug delivery.^[10] Calixarenes are used in commercial applications as sodium selective electrodes for the measurement of sodium levels in blood. Calixarenes also form complexes with cadmium, lead, lanthanides and actinides. Calix[5]arene and the C₇₀ fullerene in p-xylene form a ball-and-socket supramolecular complex.^[11] Calixarenes also form exo-calix ammonium salts with aliphatic amines such as piperidine.^[12] Derivatives or homologues of calix[4]arene exhibit highly selective binding behavior towards anions (especially halogen anions) with changes in optical properties such as fluorescence.^[13]

Calixarenes in general, and more specifically calix[4]arenes have been extensively investigated as platforms for catalysts. Some complexes compounds are active for hydrolytic reactions.^[14][15]

Calixarenes are of interest as enzyme mimetics, components of ion sensitive electrodes or sensors, selective membranes, non-linear optics

Calixarenes accelerate reactions taking place inside the concavity by a combination of local concentration effect and polar stabilization of the transition state. An extended resorcin[4]arene cavitand is found to accelerate the reaction rate of a Menshutkin reaction between quinuclidine and butylbromide by a factor of 1600.^[19]

In heterocalixarenes the phenolic units are replaced by