Guest Editorial: [2.2]Paracyclophane — After 60 Years, Stronger Than Ever

[2.2]Paracyclophane, the archetypical layered organic compound, and as such the sister molecule of sandwich compounds like ferrocene, is an amazing molecule. More than 60 years after its discovery in 1949 by Brown and Farthing, who prepared it in trace amounts by high temperature pyrolysis of p-xylene and established its structure by X-ray crystallography, this hydrocarbon not only still stands in the focus of numerous research projects, but the interest in it is actually growing rapidly. This certainly was not obvious in the beginning, and also not in the 1960 s when Donald Cram and his students started a comprehensive project (which included a new, more readily performed synthesis) to investigate the chemical behavior of this "bent and battered benzene" derivative. Cram, incidentally, also coined the term for these polycyclic compounds, pointing out that they contained cyclic, aromatic (phenyl), and saturated (the bridge) building elements. Although there is an IUPAC nomenclature to name these compounds, it is hardly used, and most chemists just use a trivial nomenclature, based on the "bridged aromatic ring" concept. As in every-day language, this nomenclature is full of contradictions and inconsistencies. Taking benzene itself as an example, the hydrocarbons with a bridge anchored in ortho-positions (e.g., tetralin, indane, all the way down to benzocyclopropene) are normally not considered cyclophanes at all, and neither are bridged annulenes such as the late Emanuel Vogel's methano[10]annulene. If the bridgehead is shifted by just one carbon atom in benzene, into the meta-, or by another one, into the para-position, respectively, these isomers are typical, and thoroughly studied, meta- and para-cyclophanes. There are several reasons why the interest in cyclophanes does not abate. As in any field of organic chemistry, the preparation of new derivatives remains of high importance — for the study of the influence of functional groups on the chemical, electronic, and structural properties of the respective cyclophane derivative, and for their use in many fields of applied and materials science, as will be discussed below. The number of functionalized [2.2]paracyclophanes has apparently not been counted yet; it must exceed several thousand by now, ranging for classical functional groups (hydroxyl, formyl, carboxyl, etc.) all the way to azides, isocyanates, metal-containing substituents, etc. A second important reason for the growing interest in substituted cyclophanes has to do with their chirality. Any monosubstituted [2.2]paracyclophane is chiral: if the substituent is incorporated into the bridge, the derivative contains a chiral center, whereas the introduction of the substituent into one of the aromatic "decks" induces planar chirality. In fact, by far the greatest number of compounds showing this stereochemical feature contain a [2.2]paracyclophane moiety. Other planar chiral compounds such as trans-cyclolefins remain the exception, one reason being their low configurational stability. Optically active [2.2]paracyclophanes begin to racemize only at temperatures above 200 °C. An additional advantage of optically active cyclophanes is the lack of an α-hydrogen atom, preventing racemization via enolization. Multiply-functionalized chiral [2.2]paracyclophanes, in particular, are rapidly becoming of interest as ligands for the preparation of chiral reagents and catalysts. It is safe to predict that this area will remain in the center of interest for a long time to come. Although early observations were made by Michael Szwarc in 1947, it took several more years until William Gorham at Union Carbide developed an efficient way to prepare a valuable polymer, named parylene, by the thermal decomposition of [2.2]paracyclophane at temperatures exceeding 550 °C and in vacuum below 1 torr. This process does not require a solvent, needs no initiator, proceeds in quantitative yield, and results in chemically resistant films free of pinholes and with excellent electric (for example, insulating) properties. The development initiated by this first application of [2.2]paracyclophane in materials science has not come to an end yet as a simple look into the internet demonstates. The term "parylene" entered into Google yields close to 250 000 results, wheras "parylene coating" provides 150 000. Many of the these links lead to technically interesting and important applications, and especially the academic scientist is encouraged to use this source more often, since it contains valuable information often overlooked in fundamental research laboratories. Whereas, in the early phase of the Gorham process, emphasis was placed on the preparation of unsubstituted parylene films, today more and more functionalized polymer films are prepared. These allow, inter alia, to bind biologically active molecules to the surface layer. Another more recent application uses cyclophanes as spacer and linker molecules. Because of cyclophanes' very rigid and stereochemically unambiguouly defined structure, all 16 hydrogen atoms, and the carbon atoms carrying them, occupy exactly fixed positions in space. The whole molecule may hence be regarded as a hexadeca-valent "superatom", into which up to 16 substituents/functional groups may be introduced. Of course, these also extend into clearly defined positions in three-dimensional space. The cyclophane spacer may hence be used as a core element to organize space (and chemical reactivity), and we envision that the first examples on the use of such spacer elements will soon find widespread further application and extension. In closing, we note that the "phane concept" connects effortlesssly to other modern areas of organic chemistry such as crown ether, cryptand, cavitand, and supramolecular chemistry. In fact, with Lüttringhaus's ansa compounds, this concept has its roots already more than 70 years ago. That natural products with a cyclophane structure are also increasingly reported in the chemical literature comes hence as no surprise. Most the aspects discussed above are dealt with in the various reviews and original contributions of this special issue of the Israel Journal of Chemistry, thus illustrating the opulently growing branches of the cyclophane tree. I take the opportunity to thank all contributors to this issue and all referees very much and hope that their efforts will find the interest of many readers. Elcya Weiss of Wiley-VCH as the managing editor is thanked for her help in keeping track of the whole editing process. 1 Henning Hopf Technische Universität Braunschweig Guest Editor