Cyclophane

Ring molecule with two nonadjacent atoms linked by a chain

In organic chemistry, a cyclophane is a hydrocarbon consisting of an aromatic unit (typically a benzene ring) and a chain that forms a bridge between two non adjacent positions of the aromatic ring. More complex derivatives with multiple aromatic units and bridges forming cagelike structures are also known. Cyclophanes are well studied examples of strained organic compounds.

Paracyclophanes adopt the boat conformation normally observed in cyclohexanes. Smaller value of n lead to greater distortions. X ray crystallography on '[6]paracyclophane' shows that the aromatic bridgehead carbon atom makes an angle of 20.5° with the plane. The benzyl carbons deviate by another 20.2°. The carbon to carbon bond length alternation has increased from 0 for benzene to 39 pm. Despite their distorted structures, cyclophanes retain their aromaticity, as determined by UV vis spectroscopy. With dimethyl acetylenedicarboxylate, [6]metacyclophane rapidly undergoes the Diels Alder reaction. A non bonding nitrogen to arene distance of 244 pm is recorded for a pyridinophane and in the unusual superphane the two benzene rings are separated by a mere 262 pm. Other representative of this group are in methylcyclophanes, in ketocyclophanes and in,in Bis(hydrosilane).

The proton NMR spectra of cyclophanes have been intensively examined to gain insights into the aromaticity of the benzene ring. Also of great interest is the shielding effects of the aromatic ring on the hydrocarbon strap. Generally the aromatic protons appear near their usual positions around 7.2 ppm, indicating that even with severe distortions, the ring retains aromaticity. The central methylene protons in the aliphatic bridge are shielded to a position of around 0.5 ppm. Metacyclophanes are generally less strained and thus more easily prepared than paracyclophanes. Shown below is the route to a [14][14]metaparacyclophane in scheme 4 featuring a in situ Ramberg Bäcklund Reaction converting the sulfone 3 to the alkene 4.

A few cyclophanes exist in nature. One example of a metacyclophane is cavicularin. Haouamine A is a paracyclophane found in a certain species of tunicate. Because of its potential application as an anticancer drug it is also available from total synthesis via an alkyne pyrone Diels Alder reaction in the crucial step with expulsion of carbon dioxide (scheme 5). In this compound the deviation from planarity is 13° for the benzene ring and 17° for the bridgehead carbons. An alternative cyclophane formation strategy in scheme 6 was developed based on aromatization of the ring well after the formation of the bridge. Two additional types of cyclophanes were discovered in nature when they were isolated from two species of cyanobacteria from the family Nostocacae. These two classes of cyclophanes are both [7,7] paracyclophanes and were named after the species from which they were extracted: cylindrocyclophanes from Cylindrospermum lichenforme and nostocyclophanes from Nostoc linckia.

B. H. Smith, Bridged Aromatic Compounds, Academic Press, New York, 1964. P. M. Keehn, S. M. Rosenfeld (eds. ), Cyclophanes, Vols. 1 and 2, Academic Press,New York, 1983. F. Vögtle, F., G. Hohner, Top. Curr. Chem. 1978, 74, 1. F. Vögtle, P. Neumann, Top. Curr. Chem. 1983, 113, 1; 1985, 115, 1.