Cyclophane Explained

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]

[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.[2] [3] Despite their distorted structures, cyclophanes retain their aromaticity, as determined by UV-vis spectroscopy.

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.[4] With dimethyl acetylenedicarboxylate, [6]metacyclophane rapidly undergoes the Diels-Alder reaction.[5]

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,[6] in-ketocyclophanes[7] and in,in-Bis(hydrosilane).[8]

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.[5]

Synthesis

[6]paracyclophane can be synthesized beginning with the Bamford–Stevens reaction to form the spiro ketone 1 in scheme 3, rearranging in a pyrolysis reaction through the carbene intermediate 4. A separate route to the Dewar form involves a Ag+-induced rearrangement reaction of the bicyclopropenyl compound 7.[9]

Metacyclophanes are generally less strained and thus more easily prepared than paracyclophanes. Shown below is the route to a [14][14]metaparacyclophane[10] in scheme 4[11] featuring a in-situ Ramberg-Bäcklund Reaction converting the sulfone 3 to the alkene 4.

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 - pyrone Diels-Alder reaction in the crucial step with expulsion of carbon dioxide (scheme 5).[12]

In this compound the deviation from planarity is 13° for the benzene ring and 17° for the bridgehead carbons.[13] An alternative cyclophane formation strategy in scheme 6[14] 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.[15] 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.

[n.n]Paracyclophanes

thumb|200px|Superphane.A well studied member of the [n.n]paracyclophane family is [2.2]paracyclophane.[16] [17] One method for its preparation is by the 1,6-Hofmann elimination of 4-methylbenzyltrimethylammonium hydroxide:[18]

The [2.2]paracyclophane-1,9-diene has been applied in ROMP to a poly(p-phenylene vinylene) with alternating cis-alkene and trans-alkene bonds using Grubbs' second generation catalyst:[19]

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:[20]

The product formed has an octahedrane skeleton. When the amine group is replaced by a methylene group no reaction takes place: the dimerization requires through-bond overlap between the aromatic pi electrons and the sigma electrons in the C-N bond in the reactants LUMO.

Janusene

The symmetrical molecule [3.3]orthocyclophane, also known as janusene, is a cyclophane that contains 4 benzene rings in a cleft-shaped arrangement. First synthesized in 1967 by Stanley J. Cristol through the cycloaddition of anthracene and dibenzobarrelene,[21] the molecule has been used to study stacking and interactions between cations and pi orbitals, particularly with silver ions.[22] Derivatives and complexes of janusene have been created to study cation-pi interactions, transannular interactions in similar rigid aromatic molecules, and systems that depend on carbon-carbon distances.

Various synthetic methods for producing janusene have been developed since the original cycloaddition reaction was discovered, including microwave assisted reactions[23] and acetylene transfer from 5,6,7,8-tetrafluorobenzobarrelene.[24]

Phanes

Generalization of cyclophanes led to the concept of phanes in the IUPAC nomenclature. Some example systematic phane names are:

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.

See also

General sources

Notes and References

  1. Book: Modern Cyclophane Chemistry. Gleiter, Rolf. Hopf, Henning. Wiley-VCH. Weinheim. 2004. 3527603964.
  2. 10.1021/ja00238a024. Synthesis and molecular structure of (Z)-[6]Paracycloph-3-enes. Journal of the American Chemical Society. 109. 4. 1136–1144. 1987. Tobe. Yoshito. Ueda. Kenichi. Kaneda. Teruhisa. Kakiuchi. Kiyomi. Odaira. Yoshinobu. Kai. Yasushi. Kasai. Nobutami.
  3. 10.1002/cber.19861190904. 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. 1986. Hunger. Jürgen. Wolff. Christian. Tochtermann. Werner. Peters. Eva-Maria. Peters. Karl. von Schnering. Hans Georg.
  4. 10.1021/ja00459a055. Interconversion of [6]paracyclophane and 1,4-hexamethylene(Dewar benzene). Journal of the American Chemical Society. 99. 17. 5815. 1977. Kammula. Seetha L.. Iroff. Linda D.. Jones. Maitland. Van Straten. J. W.. De Wolf. W. H.. Bickelhaupt. F..
  5. F. Bickelhaupt. Pure Appl. Chem.. 1990. 62. 373. 10.1351/pac199062030373. Small cyclophanes: the Bent Benzene Business. 3 . 55279751 . free.
  6. 10.1021/ja0529384. 16089445. Sterically Congestedin-Methylcyclophanes. Journal of the American Chemical Society. 127. 32. 11246–11247. 2005. Song. Qiuling. Ho. Douglas M.. Pascal. Robert A..
  7. 10.1021/ol9028572. 20112943. Anin-Ketocyclophane. Organic Letters. 12. 5. 928–930. 2010. Qin. Qian. Mague. Joel T.. Pascal. Robert A..
  8. 10.1021/ja407398w. 23971948. Exceptional Steric Congestion in an in,in-Bis(hydrosilane). Journal of the American Chemical Society. 135. 36. 13235–13237. 2013. Zong. Jie. Mague. Joel T.. Pascal. Robert A..
  9. 10.1021/ja00815a070. [6]Paracyclophane. Journal of the American Chemical Society. 96. 8. 2643–2644. 1974. Kane. Vinayak V.. Wolf. Anthony D.. Jones. Maitland.
  10. 10.1021/jo0267044. 12662074. [14][14]Metaparacyclophane: First Example of an [m][n]Metaparacyclophane. The Journal of Organic Chemistry. 68. 7. 2948–2951. 2003. Wei. Chunmei. Mo. Kai-For. Chan. Tze-Lock.
  11. Scheme 4. Reaction scheme: with para-ring in place ring closure of meta part by nucleophilic displacement of dibromide by disulfide. Then 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
  12. 10.1021/ja0602997. 16551088. Total Synthesis of (±)-Haouamine A. Journal of the American Chemical Society. 128. 12. 3908–3909. 2006. Baran. Phil S.. Burns. Noah Z.. The authors mark the biosynthetic origin as mysterious
  13. 10.1021/ol060455e. 16623580. Synthesis of the 3-Aza-[7]-paracyclophane Core of Haouamine A and B. Organic Letters. 8. 9. 1901–1904. 2006. Wipf. Peter. Furegati. Markus.
  14. Scheme 6. Reaction scheme: step I elimination reaction of methanol with trifluoroethanol and diisopropylamine, step II methylation with dimethyl sulfate. Ns = Nosylate
  15. Moore . Bradley S. . Chen . Jian Lu . Patterson . Gregory M. L. . Moore . Richard E. . Brinen . Linda S. . Kato . Yoko . Clardy . Jon . Jon Clardy . [7.7] Paracyclophanes from blue-green algae . . 112 . 10 . 4061–4063 . 1990 . 10.1021/ja00166a066.
  16. Hassan . Zahid . Spuling . Eduard . Knoll . Daniel M. . Lahann . Joerg . Bräse . Stefan . Planar chiral [2.2]paracyclophanes: from synthetic curiosity to applications in asymmetric synthesis and materials . Chemical Society Reviews . 47 . 18 . 6947–6963 . 2018 . 10.1039/C7CS00803A. 30065985 .
  17. Hassan. Zahid. Spuling. Eduard. Knoll. Daniel M.. Bräse. Stefan. Regioselective Functionalization of [2.2]Paracyclophanes: Recent Synthetic Progress and Perspectives. Angewandte Chemie International Edition. en. 59. 6. 10.1002/anie.201904863. 31283092. 1521-3773. 2019. 2156–2170. 7003812. free.
  18. 10.15227/orgsyn.042.0083. [2.2]Paracyclophane . Organic Syntheses . 1962 . 42 . 83. H. E. Winberg, F. S. Fawcett .
  19. 10.1002/anie.200602863. 17061303. Soluble Poly(p-phenylenevinylene)s through Ring-Opening Metathesis Polymerization. Angewandte Chemie International Edition. 45. 46. 7797–7800. 2006. Yu. Chin-Yang. Turner. Michael L..
  20. 10.1021/ja067350r. 17177393. 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. 2006. Okamoto. Hideki. Satake. Kyosuke. Ishida. Hiroyuki. Kimura. Masaru.
  21. Colaço . Matheus C. . Caramori . Giovanni F. . Parreira . Renato L. T. . Laali . Kenneth K. . 2022 . Janusene as a silver ion scavenger: insights from computation . New Journal of Chemistry . en . 46 . 5 . 2393–2404 . 10.1039/D1NJ03833H . 1144-0546.
  22. Mucelini . Johnatan . Østrøm . Ina . Ortolan . Alexandre O. . Andriani . Karla F. . Caramori . Giovanni F. . Parreira . Renato L. T. . Laali . Kenneth K. . 2019 . Understanding the interplay between π–π and cation–π interactions in [janusene–Ag] + host–guest systems: a computational approach ]. Dalton Transactions . en . 48 . 35 . 13281–13292 . 10.1039/C9DT02307K . 1477-9226.
  23. Štrbac . Petar . Margetić . Davor . 2020-11-14 . One-Step Synthesis of 5a,11a-Janusene Imide Employing 2,3-Dibromo-N-methylmaleimide as Acetylene Equivalent . Chemistry Proceedings . 3 . 1 . en . MDPI . 87 . 10.3390/ecsoc-24-08426. free .
  24. Cantrell . Gary L. . Filler . Robert . September 1984 . An intramolecular acetylene transfer between anthracene and 5,6,7,8-tetrafluorobenzobarrelene. A novel synthesis of janusene and dibenzobarrelene . The Journal of Organic Chemistry . en . 49 . 18 . 3406–3407 . 10.1021/jo00192a038 . 0022-3263.
  25. 10.1021/jo302186h. 23126565. Bending Benzene: Syntheses of [n]Cycloparaphenylenes. The Journal of Organic Chemistry. 77. 23. 10473–10478. 2012. Hirst. Elizabeth S.. Jasti. Ramesh.

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