Oxepines isomers

Fig. 7. Oxepine isomers 134-136 that vary as to which ring C—C bond is unsaturated the substituted dihydropyran 137 possesses the enol ether functionality of a glycal, akin to oxepine 136.

UV spectroscopy has been particularly valuable in the study of the oxepin-benzene oxide equilibration. The oxepin isomer showed absorption at 305 nm (e 900) while benzene oxide absorbed at a shorter wavelength (271 nm, e 1430) (Table 5). 

Diene moieties, reactive in [2 + 4] additions, can be formed from benzazetines by ring opening to azaxylylenes (Section 5.09.4.2.3). 3,4-Bis(trifluoromethyl)-l,2-dithietene is in equilibrium with hexafluorobutane-2,3-dithione, which adds alkenes to form 2,3-bis-(trifluoromethyl)-l,4-dithiins (Scheme 17 Section 5.15.2.4.6). Systems with more than two conjugated double bonds can react by [6ir + 2ir] processes, which in azepines can compete with the [47t + 27t] reaction (Scheme 18 Section 5.16.3.8.1). Oxepins prefer to react as 47t components, through their oxanorcaradiene isomer, in which the 47r-system is nearly planar (Section 5.17.2.2.5). Thiepins behave similarly (Section 5.17.2.4.4). Nonaromatic heteronins also react in orbital symmetry-controlled [4 + 2] and [8 + 2] cycloadditions (Scheme 19 Section 5.20.3.2.2). 

Three decades ago the preparation of oxepin represented a considerable synthetic challenge. The theoretical impetus for these efforts was the consideration that oxepin can be regarded as an analog of cyclooctatetraene in the same sense that furan is an analog of benzene. The possibility of such an electronic relationship was supported by molecular orbital calculations suggesting that oxepin might possess a certain amount of aromatic character, despite the fact that it appears to violate the [4n + 2] requirement for aromaticity. By analogy with the closely related cycloheptatriene/norcaradiene system, it was also postulated that oxepin represents a valence tautomer of benzene oxide. Other isomers of oxepin are 7-oxanorbornadiene and 3-oxaquadricyclane.1 Both have been shown to isomerize to oxepin and benzene oxide, respectively (see Section 1.1.2.1.). 

The three different benzoxepins are simply assigned by the position of the oxygen 1 -benzoxepin, 2-benzoxepin, 3-benzoxepin. Among the four possible dibenzoxepins only dibenz[6,d]oxepin and dibenz[6,/]oxepin are of importance whereas the two other isomers are only of theoretical interest because they contain unfavorable o-quinoid structures. Benzannulation across all of the C-C double bonds leads to tribenz[6,rf,/]oxepin. 

Unsubstituted oxepin reacts with methyllithium to give ew-6-methylcyclohexa-2,4-dien-l-ol216 and traces of the /runs-product,12 whereas the reaction with dimethylmagnesium gives a mixture of cis- and /rani-isomers in a ratio of 37 63.216 By using deuterated starting material it has been shown that a 1,6-addition takes place.216,217... 

Since both oxepin and its valence isomer benzene oxide contain a x-tb-diene structure they are prone to Diels-Alder addition reactions. The dienophiles 4-phenyl- and 4-methyl-4//-l,2,4-triazole-3,5-dione react with substituted oxepins at room temperature to give the 1 1 adducts 7 formed by addition to the diene structure of the respective benzene oxide.149 190,222... 

The molecules taking part in a valence tautomerization need not be equivalent. Thus, NMR spectra indicate that a true valence tautomerization exists at room temperature between the cycloheptatriene 110 and the norcaradiene (111). In this case one isomer (111) has the cw-l,2-divinylcyclopropane structure, while the other does not. In an analogous interconversion, benzene oxide and oxepin exist in a tautomeric equilibrium at room temperature. 

The parent structure, oxepin (7), exists in a state of spontaneous equilibration with the valence bond isomer benzene oxide at ambient temperature. 

The dipole moments of oxepin and benzene oxide have been calculated to be in the range 0.76-1.36 D and >1.5 D respectively using the ab initio SCF and MINDO/3 methods (80JA1255). The lower calculated dipole moment would be in accord with experimental observations where the equilibrium was found to favor oxepin (7) in less polar solvents. Coordination between the oxirane oxygen atom and polar solvent molecules would also strengthen the C—C bond of the epoxide and thus lead to a preference for the benzene oxide isomer <72AG(E)825). Thus the proportion of oxepin (7) was found by UV spectral analysis to be higher in isooctane solvent (70%) than in water-methanol (10%). 

Oxepins having annelated aromatic rings may in principle equilibrate with the valence tautomeric arene oxide forms. In practice, the equilibrium distribution will be dominated by a resonance effect, i.e. the preference for the isomer having the maximum degree of aromaticity. 

Factors which affect the oxepin-benzene oxide equilibrium positions are similarly expected to influence the thiepin-benzene episulfide distribution at equilibrium. Since however the thianorcaradiene tautomer has not to date been detected, the main evidence for this form is based upon the thermal instability and reactions of the thiepin system. Thus it is assumed that where the thianorcaradiene isomer is present, a spontaneous thermal decomposition involving extrusion of a sulfur atom will occur. Substitution at the 2,7-positions in the oxepin-arene oxide system leads to a preference for the seven-membered ring form and this effect was further enhanced by bulky substituents (e.g. Bu ). A similar effect was observed in thiepins and thus the remarkable thermal stability of (49) (2,7-r-butyl groups) and (51) (2,7-hydroxyisopropyl groups) contrasts with the behavior of thiepin (55)(2,7-isopropyl groups), which was thermally unstable even at -70 °C (78CL723). The stability of thiepin (49) results from the 2,7-steric (eclipsed) interactions which obtain in the thianorcaradiene form but which are diminished in the thiepin tautomeric form (relative to the episulfide tautomer). 

The thermal ring closure reaction of a 1,3,5-triene to a 1,3-cyclohexadiene occurs by a concerted disrotatory electrocyclic mechanism. An example of the latter is the oxepin-benzene oxide equilibrium (7) which favors the oxepin tautomer at higher temperatures (Section 5.17.1.2). Oxepin (7) was found to rearrange to phenol during attempted distillation at normal pressure (67AG(E)385>. This aromatization reaction may be considered as a spontaneous rearrangement of the oxirane ring to the dienone isomer followed by enolization (equation 7). 

The related oxobicycle (210), on photolysis in carbon tetrachloride, is converted into the isomer (211) in high yield by an intramolecular cycloaddition.186 The same transformation has been observed in norbornadiene, and other intramolecular cycloadditions are known [see, for example, Eq. (50)187]. An intermediate of this type has been postulated188 to account for the photorearrangement of 1,4-epoxy -1,4-dihydronaphthalene to benz[/]oxepin [Eq. (51)]. 

Relatively few examples of photoreactions of seven-membered and larger heterocycles have been reported. The major products of irradiation of liquid oxepin are hex-5-en-l-ol and hexanal234 photodecomposition of cyclic ethers has, in general been shown to be largely dependent on ring size. Irradiation of the valence bond isomer (287) of hexakis(trifluoromethyl) oxepin gave the unexpectedly stable oxet (288) via a mixture of (Z)- and... 

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