3-Benzoxepin

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3-Benzoxepin
3-Benzoxepin-Struktur.svg
Names
Preferred IUPAC name
3-Benzoxepine
Identifiers
3D model (JSmol)
ChemSpider
PubChem CID
  • InChI=1S/C10H8O/c1-2-4-10-6-8-11-7-5-9(10)3-1/h1-8H
    Key: APSZPCTXHHKIQO-UHFFFAOYSA-N
  • C1=CC=C2C=COC=CC2=C1
Properties
C10H8O
Molar mass 144.173 g·mol−1
AppearanceYellow solid [1]
Melting point 84 (83–84 °C; [2] 84 °C [1] )
Solubility soluble in apolar solvents (diethyl ether, benzene, tetrachloromethane) [3] and alcohols (methanol) [2]
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).

3-Benzoxepin is an annulated ring system with an aromatic benzene ring and a non-aromatic, unsaturated, oxygen-containing seven-membered heterocyclic oxepin. The first synthesis was described by Karl Dimroth and coworkers in 1961. [1] It is one of the three isomers of the benzoxepins.

Contents

Occurrence and synthesis

3-Benzoxepin itself is a non-natural compound, but the bicyclic ring system is part of the naturally occurring compounds perilloxin (I) from Perilla frutescens (variant acuta), [4] tenual (II), and tenucarb (III) from Asphodeline tenuior . [5] Perilloxin inhibits the enzyme cyclooxygenase with an IC50 of 23.2 μM. [4] Non-steroidal anti-inflammatory drugs like aspirin and ibuprofen also work by inhibiting the cyclooxygenase enzyme family. [6]

Structural formulas of perilloxin, tenual, and tenucarb Perilloxin+Tenual+Tenucarb.svg
Structural formulas of perilloxin, tenual, and tenucarb

Unsubstituted 3-benzoxepin can be synthesized through a double Wittig reaction from o-phthalaldehyde with bis-(α,α′-triphenylphosphonium)-dimethylether-dibromide. [2] The latter compound can be synthesized from α,α′-dibromodimethyl ether (bis(bromomethyl)ether or BBME) which is accessible from hydrobromic acid, paraformaldehyde, [7] and triphenylphosphine. The reaction is performed in dry methanol with sodium methoxide, and the product is obtained in 55% yield. [1] [3]

Synthesis from 3-benzoxepin according to K. Dimroth Synthese von 3-Benzoxepin.svg
Synthesis from 3-benzoxepin according to K. Dimroth

The compound can also be obtained through UV-irratiation of certain naphthalene derivatives such as 1,4-epoxy-1,4-dihydronaphthalene. [8]

3-Benzoxepin from UV-irradiation from epoxydihydronaphthaline 3-Benzoxepin aus Epoxydihydronaphthalin.svg
3-Benzoxepin from UV-irradiation from epoxydihydronaphthaline

It can also be obtained by photooxidation of 1,4-dihydronaphthalene, followed by pyrolysis of the formed hydroperoxides. [9]

3-Benzoxepin durch Pyrolyse aus Hydroperoxydihydronaphthalen 3-Benzoxepin aus Hydroperoxydihydronaphthalen.svg
3-Benzoxepin durch Pyrolyse aus Hydroperoxydihydronaphthalen

The latter syntheses give 3-benzoxepins in low yields (4–6%). [8]

Properties

3-Benzoxepin is a bright yellow solid that crystallizes in platelets, with a smell similar to naphthalene. The material is soluble in apolar, organic solvents. Like naphthalene, it can be purified through sublimation. The solid is relatively acid-resistant, only under refluxing in concentrated, acidic alcohol solutions an unsaturated aldehyde is formed (likely an indene-3-aldehyde). Catalytic hydrogenation with a palladium catalyst results in 1,2,4,5-tetrahydro-3-benzoxepin.

Reactions with 3-Benzoxepin Reaktionen an 3-Benzoxepin.svg
Reactions with 3-Benzoxepin

References

  1. 1 2 3 4 Dimroth, K.; Pohl, G. (1961). "3-Benzoxepin". Angew. Chem. 73 (12): 436. Bibcode:1961AngCh..73..436D. doi:10.1002/ange.19610731215.
  2. 1 2 3 Dimroth, K.; Pohl, G.; Follmann, H. (1966). "Die Synthese von Derivaten des 3-Oxepins und des Furans durch eine zweifache Wittig-Reaktion". Chem. Ber. (in German). 99 (2): 634–641. doi:10.1002/cber.19660990238.
  3. 1 2 Rosowsky, A., ed. (1972). "II. Oxepin Ring Systems Containing Two Rings". Seven-Membered Heterocyclic Compounds Containing Oxygen and Sulfur. The Chemistry of Heterocyclic Compounds (in German). Vol. 26th. New York: Wiley-Interscience. p. 96. ISBN   0-471-38210-8.
  4. 1 2 Liu, J.-H.; Steigel, A.; Reininger, E.; Bauer, R. (2000). "Two new prenylated 3-benzoxepin derivatives as cyclooxygenase inhibitors from Perilla frutescens var. acuta". J. Nat. Prod. 63 (3): 403–405. doi:10.1021/np990362o. PMID   10757731.
  5. ↑ Ulubelen, A.; Tuzlaci, E.; Atilan, N. (1989). "Oxepine derivatives and anthraquinones from Asphodeline tenuior and A. taurica". Phytochemistry . 28 (2): 649–650. Bibcode:1989PChem..28..649U. doi:10.1016/0031-9422(89)80076-7.
  6. ↑ Kester, M.; Karpa, K. D.; Vrana, K. E. (2011). "NSAIDs". Pharmacology. Elsevier's Integrated Review. Elsevier Health Sciences. pp. 165–166. ISBN   9780323074452.
  7. ↑ USpatent 20040242799,Grabarnick, M.&Sasson, Y.,"Process to bromomethylate aromatic compounds",published 2004-12-02, assigned to Grabarnick, M.and Sasson, Y.
  8. 1 2 Ziegler, G. R. (1969). "Mechanisms of photochemical reactions in solution. LVII. Photorearrangement of 1,4-epoxy-1,4-dihydronaphthalene to benz[f]oxepin". J. Am. Chem. Soc. 91 (2): 446–449. doi:10.1021/ja01030a040.
  9. ↑ Jeffrey, A. M.; Jerina, D. M. (1972). "Autoxidation of 1,4-dihydronaphthalene. Formation of 3-benzoxepin via pyrolysis of 2-hydroperoxy-1,2-dihydronaphthalene". J. Am. Chem. Soc. 94 (11): 4048–4049. doi:10.1021/ja00766a084.
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