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.[1][2]
[n]-Cyclophanes
Structures
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.[3][4] Despite their distorted structures, cyclophanes retain their
aromaticity, as determined by
UV-vis spectroscopy.[1]
Reactivity
With regards to their reactivity, cyclophanes often exhibit diene-like behavior, despite evidence for aromaticity in even the most distorted [6]-cyclophane. This highly distorted cyclophane
photochemically converts to the
Dewar benzene derivative. Heat reverses the reaction.[5]
With
dimethyl acetylenedicarboxylate, [6]metacyclophane rapidly undergoes the
Diels-Alder reaction.[6]
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,[7] in-ketocyclophanes[8] and in,in-Bis(hydrosilane).[9]
NMR properties
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.[6]
Metacyclophanes are generally less strained and thus more easily prepared than paracyclophanes. Shown below is the route to a [14][14]metaparacyclophane[11] in scheme 4[12] featuring a in-situ
Ramberg-Bäcklund Reaction converting the
sulfone3 to the
alkene4.
Naturally occurring [n]-cyclophanes
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 -
pyroneDiels-Alder reaction in the crucial step with expulsion of carbon dioxide (scheme 5).[13]
In this compound the deviation from planarity is 13° for the benzene ring and 17° for the bridgehead carbons.[14] An alternative cyclophane formation strategy in scheme 6[15] 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.[16] 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.
The driving force for ring-opening and polymerization is strain relief. The reaction is believed to be a
living polymerization due to the lack of competing reactions.
Because the two benzene rings are in close proximity this cyclophane type also serves as guinea pig for
photochemicaldimerization reactions as illustrated by this example:[21]
Generalization of cyclophanes led to the concept of
phanes in the IUPAC nomenclature. Some example systematic phane names are:
[14]metacyclophane is 1(1,3)-benzenacyclopentadecaphane
[2.2']paracyclophane (or [2.2]paracyclophane) is 1,4(1,4)-dibenzenacyclohexaphane
In "1(1,3)-benzenacyclopentadecaphane", the "1" refers to the first position of the ring as a "superatom", the "(1,3)" describes the "meta" location, "benzena" refers to the ring, and the "pentadeca" (15) describes the chain length counting the ring as one atom.
^Tobe, Yoshito; Ueda, Kenichi; Kaneda, Teruhisa; Kakiuchi, Kiyomi; Odaira, Yoshinobu; Kai, Yasushi; Kasai, Nobutami (1987). "Synthesis and molecular structure of (Z)-[6]Paracycloph-3-enes". Journal of the American Chemical Society. 109 (4): 1136–1144.
doi:
10.1021/ja00238a024.
^Hunger, Jürgen; Wolff, Christian; Tochtermann, Werner; Peters, Eva-Maria; Peters, Karl; von Schnering, Hans Georg (1986). "Synthese mittlerer und großer Ringe, XVI. Bootförmige Arene — Synthese, Struktur und Eigenschaften von [7]Paracyclophanen und [7](1,4)Naphthalinophanen". Chemische Berichte. 119 (9): 2698–2722.
doi:
10.1002/cber.19861190904.
^Kammula, Seetha L.; Iroff, Linda D.; Jones, Maitland; Van Straten, J. W.; De Wolf, W. H.; Bickelhaupt, F. (1977). "Interconversion of [6]paracyclophane and 1,4-hexamethylene(Dewar benzene)". Journal of the American Chemical Society. 99 (17): 5815.
doi:
10.1021/ja00459a055.
^Song, Qiuling; Ho, Douglas M.; Pascal, Robert A. (2005). "Sterically Congestedin-Methylcyclophanes". Journal of the American Chemical Society. 127 (32): 11246–11247.
doi:
10.1021/ja0529384.
PMID16089445.
^Qin, Qian; Mague, Joel T.; Pascal, Robert A. (2010). "Anin-Ketocyclophane". Organic Letters. 12 (5): 928–930.
doi:
10.1021/ol9028572.
PMID20112943.
^Zong, Jie; Mague, Joel T.; Pascal, Robert A. (2013). "Exceptional Steric Congestion in an in,in-Bis(hydrosilane)". Journal of the American Chemical Society. 135 (36): 13235–13237.
doi:
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PMID23971948.
^
abKane, Vinayak V.; Wolf, Anthony D.; Jones, Maitland (1974). "[6]Paracyclophane". Journal of the American Chemical Society. 96 (8): 2643–2644.
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^Wei, Chunmei; Mo, Kai-For; Chan, Tze-Lock (2003). "[14][14]Metaparacyclophane: First Example of an [m][n]Metaparacyclophane". The Journal of Organic Chemistry. 68 (7): 2948–2951.
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^Baran, Phil S.; Burns, Noah Z. (2006). "Total Synthesis of (±)-Haouamine A". Journal of the American Chemical Society. 128 (12): 3908–3909.
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PMID16551088. The authors mark the biosynthetic origin as mysterious
^Wipf, Peter; Furegati, Markus (2006). "Synthesis of the 3-Aza-[7]-paracyclophane Core of Haouamine A and B". Organic Letters. 8 (9): 1901–1904.
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^Moore, Bradley S.; Chen, Jian Lu; Patterson, Gregory M. L.; Moore, Richard E.; Brinen, Linda S.; Kato, Yoko;
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^Hassan, Zahid; Spuling, Eduard; Knoll, Daniel M.; Lahann, Joerg; Bräse, Stefan (2018). "Planar chiral [2.2]paracyclophanes: from synthetic curiosity to applications in asymmetric synthesis and materials". Chemical Society Reviews. 47 (18): 6947–6963.
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^H. E. Winberg, F. S. Fawcett (1962). "[2.2]Paracyclophane". Organic Syntheses. 42: 83.
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^Yu, Chin-Yang; Turner, Michael L. (2006). "Soluble Poly(p-phenylenevinylene)s through Ring-Opening Metathesis Polymerization". Angewandte Chemie International Edition. 45 (46): 7797–7800.
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^Okamoto, Hideki; Satake, Kyosuke; Ishida, Hiroyuki; Kimura, Masaru (2006). "Photoreaction of a 2,11-Diaza[3.3]paracyclophane Derivative: Formation of Octahedrane by Photochemical Dimerization of Benzene". Journal of the American Chemical Society. 128 (51): 16508–16509.
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^Hirst, Elizabeth S.; Jasti, Ramesh (2012). "Bending Benzene: Syntheses of [n]Cycloparaphenylenes". The Journal of Organic Chemistry. 77 (23): 10473–10478.
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