Cyclophane
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2008-04-23T13:11:43Z
Vina-iwbot
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robot Modifying: [[pl:Cyklofany]]
[[Image:Cyclophanes.png|300px|right|Scheme 1. Cyclophanes]]A '''cyclophane''' is a [[hydrocarbon]] consisting of an [[aromatic]] unit (typically a [[benzene]] ring) and an [[aliphatic]] [[Chain (sequence)|chain]] that forms a [[bridge]] between two non-adjacent positions of the aromatic ring. More complex derivatives with multiple aromatic units and bridges forming [[cage]]like [[structure]]s are also known. Cyclophanes are well studied in [[organic chemistry]] because they adopt unusual chemical conformations due to build-up of [[Strain (chemistry)|
strain]]. Despite this, cyclophane structures are not unknown to biomolecules.
[[Image:-6-cyclophanes.png|300px|right|Scheme 2. [6]paracyclophanes]]Basic cyclophane types are '''[n]metacyclophanes''' ('''I''') in ''scheme 1'', '''[n]paracyclophanes''' ('''II''') and '''[n,n']cyclophanes''' ('''III'''). the prefixes ''meta'' and ''para'' correspond to the usual [[arene substitution patterns]] and n refers to the number of atoms making up the bridge.
==Structure==
Paracyclophanes adopt the [[boat conformation]] normally observed in cyclohexanes but are still able to retain [[aromaticity]]. The smaller the value of n the larger the deviation from aromatic planarity. In [6]paracyclophane which one of the stable cyclophanes [[X-ray crystallography]] 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 [[picometer|pm]] <ref>''Synthesis and molecular structure of (Z)-[6]Paracycloph-3-enes'' Yoshito Tobe, Kenichi Ueda, Teruhisa Kaneda, Kiyomi Kakiuchi, Yoshinobu Odaira, Yasushi Kai, Nobutami Kasai [[J. Am. Chem. Soc.]]; '''1987'''; 109(4); 1136-1144. [http://pubs.acs.org/cgi-bin/abstract.cgi/jacsat/1987/109/i04/f-pdf/f_ja00238a024.pdf Abstract]</ref> <ref>J. Hunger, C. Wolff, W. Tochtermann, E-M. Peters, K.Peters, H.G. von Schering [[Chem. Ber.]], 119, 2698 ('''1986''')</ref>.
In organic reactions [6]cyclophane tends to react as a diene derivative and not as an aromat. With [[bromine]] it gives 1,4-addition and with [[chlorine]] the 1,2-addition product forms.
Yet the [[proton NMR]] spectrum displays the aromatic protons and their usual deshielded positions around 7.2 ppm and the central methylene protons in the aliphatic bridge are even severely deshielded to a position of around - 0.5 ppm, that is, even deshielded compared to the internal reference [[tetramethylsilane]]. With respect to the [[diamagnetic ring current]] criterion for aromaticity this cyclophane is still aromatic.
[[Image:Incyclophanes.png|right|400px|In-cyclophanes, pyridinophanes and superphanes]]
One particular research field in cyclophanes involves probing just how close atoms can get above the center of an aromatic nucleus <ref>''Molecular Iron Maidens: Ultrashort Nonbonded Contacts in Cyclophanes
and Other Crowded Molecules'' Robert A. Pascal, Jr Eur. J. Org. Chem. '''2004''', 3763-3771
{{DOI|10.1002/ejoc.200400183}}</ref>. In so-called '''in-cyclophanes''' with part of the molecule forced to point '''in'''wards one of the closest hydrogen to arene distances experimentally determined is just 168 [[picometer]].
A non-bonding nitrogen to arene distance of 244 pm is recorded for a pyridinophane and in the totally weird [[superphane]] the two benzene rings are separated by a mere 262 pm. Another representative of this group are [[in-methylcyclophane]]s.
==Synthetic methods==
[6]paracyclophane can be synthesized <ref>''[6]Paracyclophane'' Vinayak V. Kane, Anthony D. Wolf, Maitland Jones, , Jr. [[J. Am. Chem. Soc.]]; '''1974'''; 96(8); 2643-2644. [http://pubs.acs.org/cgi-bin/abstract.cgi/jacsat/1974/96/i08/f-pdf/f_ja00815a070.pdf Abstract]</ref> <ref>''Interconversion of [6]paracyclophane and 1,4-hexamethylene(Dewar benzene)'' Seetha L. Kammula, Linda D. Iroff, Maitland Jones, , Jr. J. W. Van Straten, W. H. De Wolf, F. Bickelhaupt [[J. Am. Chem. Soc.]]; '''1977'''; 99(17); 5815-5815. [http://pubs.acs.org/cgi-bin/abstract.cgi/jacsat/1977/99/i17/f-pdf/f_ja00459a055.pdf Abstract]</ref> in the laboratory by a [[Bamford-Stevens reaction]] with [[spiro compound|spiro]] [[ketone]] '''1''' in ''scheme 3'' rearranging in a [[pyrolysis]] reaction through the [[carbene]] intermediate '''4'''. The cyclophane can be [[photochemistry|photochemically]] converted to the [[Dewar benzene]] '''6''' and back again by application of heat. A separate route to the Dewar form is by a cationic [[silver perchlorate]] induced [[rearrangement reaction]] of the bicyclopropenyl copound '''7'''.
[[Image:-6-cyclophaneSynthesis.png|500px|center|Scheme 3. [6]paracyclophane synthesis]]
'''Metaparacyclophanes''' constitute another class of cyclophans like the [14][14]metaparacyclophane <ref>''[14][14]Metaparacyclophane: First Example of an [m][n]Metaparacyclophane''Chunmei Wei, Kai-For Mo, and Tze-Lock Chan [[J. Org. Chem.]]; '''2003'''; 68(7) pp 2948 - 2951; (Note) [http://dx.doi.org/10.1021/jo0267044 Abstract]</ref> in ''scheme 4'' <ref><small>Scheme 4. Reaction scheme: with para-ring in place ring closure of meta part by [[nucleophilic displacement]] of [[alkyl halide|dibromide]] by [[sulfide|disulfide]]. Then [[organic oxidation|oxidation]] of sulfide to [[sulfone]] by [[hydrogen peroxide]] followed by in-situ [[Ramberg-Bäcklund Reaction]] with halide donor dibromodifluoromethane and base [[potassium hydroxide]]. Final step [[hydrogenation]] pf [[alkene]] by hydrogen and [[palladium on carbon]]</small></ref> featuring a in-situ [[Ramberg-Bäcklund Reaction]] converting the [[sulfone]] '''3''' to the [[alkene]] '''4'''.
[[Image:Metaparacyclophane.png|600px|center|Scheme 4. [14][14]metaparacyclophane]]
== Naturally occurring cyclophanes ==
Despite carrying strain, the cyclophane motif does 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'') <ref>''Total Synthesis of (±)-Haouamine A'' Phil S. Baran and Noah Z. Burns [[J. Am. Chem. Soc.]]; '''2006'''; ASAP Web Release Date: 04-Mar-2006; [http://dx.doi.org/10.1021/ja0602997 Abstract] <small>The authors mark the biosynthetic origin as ''mysterious''</ref>.
[[Image:Haouamine.png|500px|center|Scheme 5. Haouamine A]]
In this compound the deviation from planarity is 13° for the benzene ring and 17° for the bridgehead carbons <ref>''Synthesis of the 3-Aza-[7]-paracyclophane Core of Haouamine A and B'' Peter Wipf and Markus Furegati Org. Lett.; '''2006'''; 8(9) pp 1901 - 1904; (Letter) [http://dx.doi.org/10.1021/ol060455e Abstract]</ref>. An alternative cyclophane formation strategy in ''scheme 6'' <ref>Scheme 6. Reaction scheme: step I [[elimination reaction]] of methanol with [[trifluoroethanol]] and [[diisopropylamine]], step II [[methylation]] with [[dimethyl sulfate]]. Ns = [[Nosylate]] </ref> was developed based on [[aromatization]] of the ring well after the formation of the bridge.
[[Image:Haouamine aromatization.png|500px|center|Scheme 6. Haouamine cyclophane substructure synthesis]]
==[n,n]Paracyclophanes==
A well exploited member of the [n,n]paracyclophane family is '''[2,2]paracyclophane'''. One method for its preparation is by a [[Hofmann elimination|1,6-Hofmann elimination]] <ref>[[Organic Syntheses]], Coll. Vol. 5, p.883 ('''1973'''); Vol. 42, p.83 ('''1962''') [http://www.orgsyn.org/orgsyn/orgsyn/prepContent.asp?prep=cv5p0883 Link].</ref>:
[[Image:2,2-paracyclophane.png|center|400px|Scheme 7. 2,2-paracyclophane synthesis]]
The [2.2]paracyclophane-1,9-diene has been applied in [[Ring opening metathesis polymerisation|ROMP]] to a [[poly(p-phenylene vinylene)]] with alternating [[cis-alkene]] and [[trans-alkene]] bonds using [[Grubb's second generation catalyst]] <ref>''Soluble Poly(p-phenylenevinylene)s through Ring-Opening Metathesis Polymerization'' Chin-Yang Yu and Michael L. Turner [[Angew. Chem. Int. Ed.]] '''2006''', 45, 7797 –7800 {{DOI|10.1002/anie.200602863}}</ref>:
[[Image:2,2-paracyclophanedienePolymerization.png|center|400px|Scheme 8. 2,2-paracyclophane-1,9-diene polymerization]]
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 [[photochemical]] [[dimerization]] reactions as illustrated by this example <ref>''Photoreaction of a 2,11-Diaza[3.3]paracyclophane Derivative: Formation of Octahedrane by Photochemical Dimerization of Benzene'' Hideki Okamoto, Kyosuke Satake, Hiroyuki Ishida, and Masaru Kimura [[J. Am. Chem. Soc.]]; '''2006'''; 128(51) pp 16508 - 16509; (Communication) {{DOI|10.1021/ja067350r}}</ref>:
[[Image:CyclophaneOctahedraneFormation.png|center|400px|Formation of Octahedrane by Photochemical Dimerization of Benzene]]
The product formed has an [[octahedrane]] skeleton. Interestingly when the [[amine]] group is replaced by a [[methylene]] group no reaction takes place: the dimerization requires [[through-bond electron transfer|through-bond overlap]] between the aromatic [[pi electron]]s and the [[sigma bond|sigma electrons]] in the C-N bond in the reactants [[LUMO]].
==References==
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[[Category:Hydrocarbons]]
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