3-Benzoxepin

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.

3-Benzoxepin

Names
Preferred IUPAC name 3-Benzoxepine
Identifiers
CAS Number	264-13-1
3D model (JSmol)	Interactive image
ChemSpider	2892804
PubChem CID	3659427
CompTox Dashboard (EPA)	DTXSID401029265
InChI InChI=1S/C10H8O/c1-2-4-10-6-8-11-7-5-9(10)3-1/h1-8H Key: APSZPCTXHHKIQO-UHFFFAOYSA-N
SMILES C1=CC=C2C=COC=CC2=C1
Properties
Chemical formula	C10H8O
Molar mass	144.173 g·mol−1
Appearance	Yellow 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). Infobox references

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

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

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

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

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