Benzene oxide-oxepin equilibrium

The first catalytic enantioselective trapping of benzene oxide-oxepine equilibrium mixture with an organometallic reagent is reported. The catalyst system included copper ditriflate and (llbi )-iV,./V-bis[(lR)-l-phenylethyl]di-naphtho[2,l- l, 2 -/][l,3,2]dioxaphosphepin-4-amine. The products of the reaction with dimethylzinc were (lA,65 )-6-methyl-2,4-cyclohexadien-l-ol in 93% ee and 4-methyl-2,5-cyclohexadien-l-ol <2001CC2606>. 

Benzene oxide-oxepin equilibrium, 326-27 Benzbydrol, 397 Benzocyclobutene, 3S0, 433 Benzonorbonadienes. substituted. 437 Benzophenone.267-68. 407, 424, 467 Jablonski diagram, 232 oxciane formation, 407, 424 phoioreduction, 397-98,467 as sensitizer, 294, 367, 407 substituted. 32 Benzopinacol, 397 Benzoyloxy chromophore, 134 Benzvaiene, 264-63, 302,448-31 Benzyl anion and cation, 171 Benzyl radical, 102 Biacctyl, 266. 291, 423,469 Jablonski energy diagram, 231 9,9 -Bianthryl, 48... 

In contrast, the parent benzene oxide-oxepin equilibrium is quite evenly balanced." In nonpolar solvents, 39 is rather stable at RT, but in acetonitrile or acetone it rearranges spontaneously to hexafluorocyclohexa-2,4-dienone (42), presumably via zwitterion 41. 

Gunther, H. P.M.R. Spectroscopy of unsaturated ring systems. II. Detection and kinetics of benzene oxide-oxepine equilibrium. Tetrahedron Lett. 1965, 6, 4085. 

Thermodynamic parameters for the benzene oxide-oxepine system are calculated at MP4(SDQ)/6-31+G //HF/ 6-31G level of theory. The effect of solvent polarity on the above equilibrium is studied using the isodensity polarized continuum method. Low polar solvents favor the oxepine formation, whereas medium to high polar solvents lead to benzene oxide formation. The transition state for the tautomerization is fully characterized and the activation energies for the forward and reverse reaction are estimated to be ca. 9.5 and 11.0 kcal mol-1, respectively. The solvent polarity exerts a reasonable effect decreasing the activation energies up to 4 kcal mol-1 <2001MI471>. 

Preferred geometry of the benzene oxide-oxepin system can be predicted by molecular orbital methods. Thus benzene oxide la is predicted to be markedly non-planar (with the epoxide ring at an angle of 73° to the benzene ring), while the oxepin lb has been predicted to prefer a shallow boat structure (MINDO/3) or a planar structure ab initio) As previously mentioned, the proportion of each tautomer present at equilibrium is both temperature and solvent-dependent. Molecular orbital calculations have been used to rationalize the solvent effects, both in terms of the more polar character of the arene oxide that is favored in polar solvents and the strengthening of the oxirane C-C bond upon coordination of the oxygen atom lone pair in polar solvents. Thus values in the range 1.5-2.0 D and 0.76-1.36 D for the dipole moments of arene oxide la and oxepin lb have been calculated. 

Dewar pyridine, 2-azabicyclo[2.2.0]hexa-2,5-diene (218), thermally reverted to pyridine at room temperature with a half-life time of 2.5 minutes (Ea = 16 kcal/mol).255 Far more stable were 2-azabicyclo-[2.2.0]hex-5-en-3-ones (225).265-267 The kinetics of the thermal (2 + 2)-cycloreversion of 225 (R = Me) in the temperature range of 130° to 160° have been reported (A//J = 33.2 kcal mol-1 ASt = + 2.7 cal mol-1 deg-1).266 An interesting difference in rate was observed between 225 (R = H) and its methyl homolog 225 (R = Me). At 130° the former reverted ten times as rapidly to 2-pyridone as the latter did to 1-methyl-2-pyridone this difference has been related to the intermediacy of the lactim tautomer of 225 (R = H) in the former reaction. Dewar benzene oxide, 2,3-epoxybicyclo[2.2.0]hex-5-ene (266), isomerized to an equilibrium mixture of benzene oxide/oxepin at 115° with a half-life time of 18 minutes.270 The relatively high thermal stability of such strained bicyclic heterocycles has been attributed to the fact that the symmetry-allowed conrotatory process would give rise to an unfavored cis.trans heterocyclic diene.265... 

The synthesis of monocyclic oxepins [7] can start from 3,4-dibromo-7-oxabicyclo-[4.1.0]heptanes 14, which are readily accessible from cyclohexa-1,4-dienes by monoe-poxidation providing 13, followed by bromine addition to the remaining double bond twofold dehydrobromination of 14 with methojdde or l,8-diazabicyclo[5.4.0]undec-7-ene (DBU) yields the equilibrium mixture benzene oxide/oxepin ... 

Oxabicyclo[4.1.0]hept-3-enes with a bromo substituent in position 2 can be converted to oxepins 11 by reaction with an appropriate base such as potassium ter+butoxide or triethylamine (see the experimental procedures for the preparation of the parent system in Houben-Weyl, Vol. 6/ld, pi78 and Vol. 6/4, p462).12,156,157 Usually the reaction products are mixtures of oxepin 11 and benzene oxide 12. In the case of ZerZ-butyl 7-oxabicyclo[4,1.0]hept-3-ene-2-carboxylate, the equilibrium lies completely on the benzene oxide side 12a.158... 

The equilibrium between oxepin and benzene oxide created interest in performing Diels-Alder reactions trapping one or both isomeric structures.1 The reaction of maleic anhydride or maleic imide with oxepin and substituted derivatives gives products 1 derived from the addition of the dienophile to the benzene oxide structure.2-l4-126 14 9 156 158 228 231-259... 

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. 

Oxepin is in equilibrium with benzene oxide by a [3,3]-sigmatropic shift. Advantage has been taken of this equilibrium to develop a short synthesis of barrelene. Outline a way that this could be done. 

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%). 

The effect of temperature upon the oxepin-benzene oxide equilibrium has been investigated by NMR and UV methods (67AG(E)385). At lower temperatures the benzene oxide tautomer is preferred. At higher temperatures it is not possible to estimate the proportion of oxepin tautomer by NMR due to the rapid exchange rate. UV spectroscopy however indicates that the proportion of oxepin increases with increasing temperature. 

Similarly, the fusion of an aromatic ring to the oxepin-benzene oxide system was found to drive the equilibrium toward extremes in either direction. The calculated resonance energies for oxepins (26), (27) and (28) were 4.81, 78.46 and 81.72 kJ mol-1 respectively (70T4269). These calculated values concur with experimental observations since oxepins (27) and (28) have been synthesized and are relatively stable compounds. The formation of 2-benzoxepin (26) from naphthalene 1,2-oxide would involve a considerable loss in resonance energy to the system and has not been detected spectroscopically (67AG(E)385). 

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). 

Some of the reagents used in olefin epoxidation can be applied in the direct oxidation of arenes to arene oxides. Benzene oxide, however, like other arene oxides, exists in equilibrium with oxepin, its valence tautomer, and has not been isolated. Existence of benzene oxides as intermediates can be concluded from observations like the NIH shift discussed above.752,753... 

Using both semi-empirical and ab initio calculations the study of oxepin (6), benzene oxide (7), and their equilibrium (Scheme 2) has been conducted. The fully optimized geometry (90MI902-01) agrees with that experimentally found for several substituted oxepines. The carbon skeleton of benzene oxide is practically planar while the angle between the epoxide ring and the adjacent plane is ca. 106°. The oxepin molecule is boat-shaped with a fold angles between C2—C7 and C3—C6 of ca. 137 and 159°, respectively. 

Substitution of methyl groups on the oxirane ring tilts the stability of the tautomers in favor of oxepin. Thus 1-methylbenzene oxide (154) exists as 2-methyloxepin (155), in rapid equilibrium with the benzene oxide tautomer 154.74 The AH has been calculated as 0.4 0.02 kcal/mol, i.e., 1.3 kcal/mol... 

Both the monomethylbenzene oxide 153-155, which exists in dynamic equilibrium with a predominant oxepin component, and 2,7-dimethyloxepin (157), with almost no benzene oxide component (156), in equilibrium at ambient temperature, react with maleic anhydride and dimethyl acetylenedi-carboxylate to give the Diels-Alder adducts 175 and 176, respectively, resulting from reaction with the oxide form.8... 

Trapping of the oxepine 104 (R1 = R2 = Me in equilibrium with the corresponding benzene-oxide 103) with 4-phenyl-l,2,4-triazoline-3,5-dione 105 has been reported to give the Ws-adduct 106, whose structure was confirmed by X-ray analysis. Diels-Alder adducts 107 of the benzene-oxides were also observed [02CC1956],... 

Many arene oxides are in dynamic equilibrium with their oxepin forms. The parent molecules, benzene oxide la and oxepin lb, are related as valence tautomers that interconvert by an allowed disrotatory electrocyclic reaction. Structural identification of la and lb was based initially upon spectroscopic evidence and chemical transformation to stable products of known structure. Thus the arene-oxide structure was inferred from its typical dienoid (4 + 27t cycloaddition) and epoxide (ring-opening, aromatization) reactions, while the oxepin structure was deduced by catalytic hydrogenation of the triene oxepin to form oxepane. 

While the isomerization of benzene oxides to oxepins occurs spontaneously at low temperature, the analogous mobile valence tautomerization of m-benzene dioxide 143 (Figure 10) to the 10-tt-heterocycle, 1,4-dioxocin, was only evident at temperatures > 50°The latter process is symmetry-allowed and is formally equivalent to a retro-Diels-Alder reaction. The mobile equilibrium at 60°C appeared... 

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