3-Benzoxepin is an annulated ring system with an aromatic benzene ring and a non-aromatic, unsaturated, oxygen-containing seven-membered heterocyclicoxepin. The first synthesis was described by Karl Dimroth and coworkers in 1961.[1] It is one of the three isomers of the benzoxepins.
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.[3] 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][2]
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 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.
^ abRosowsky, 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. ISBN0-471-38210-8.
^ abcDimroth, 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.
^ abLiu, 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. PMID10757731.
^US patent 20040242799, Grabarnick, M. & Sasson, Y., "Process to bromomethylate aromatic compounds", published 2004-12-02, assigned to Grabarnick, M. and Sasson, Y.
^ abZiegler, 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.
^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.
