Benzene oxide, from oxepin

It should be mentioned that an end-product analysis was carried out by gas chromatography. The only product detected corresponded to the retention time of phenol. However, if benzene oxide and oxepin were present, they may have isomerized to phenol during the process of collection and passage through the chromatographic column, or the retention times may have been indistinguishable from that of phenol. (Authentic samples of oxepin and benzene oxide were not available to test these points). 

The production of toluene 1,2-epoxide (C) and 2-methy oxepin (D) by the pathway (b) was proposed by Klotz et al. (2000). Their reaction rates with OH was found to be fast experimentally and theoretically, and they are thought to be one of the formation pathways to the open-ring compounds described below (Cartas-Rosado and Castro 2007). In the case of benzene, it has been reported that phenol is formed from the photolysis of benzene oxide and oxepin (Klotz et al. 1997), but the cresols are not formed from toluene 1.2-epoxide or 2-methyl oxepin (Klotz et al. 2000). 

The knowledge of the valence tautomerization of benzene oxides to oxepins12 prompted several groups to synthesize oxepins by dehydrohalogenation of 7-oxabicyclo[4.1.0]heptane derivatives. Numerous examples have been described for the base-catalyzed elimination of hydrogen bromide from the 3,4-dibromo-7-oxabicyclo[4.1.0]heptane system. The reaction products are usually obtained as mixtures of oxepin 1 and benzene oxide 2. The 2,7-bis(hydroxy-methyl)oxepin 1 p obtained by this route can be converted to the 2,7-dicarbaldehyde with man-ganese(IV) oxide.23... 

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... 

In 1-benzoxepins the benzene oxide form is energetically unfavorable. Thus, the adducts 5 formed with dienophiles such as ethenetetracarbonitrile arise from the oxepin structure with the nonaromatic double bonds as diene fragment.233 The yields of these reactions arc almost quantitative. 

For example, Klotz et al. (1997, 1998) have shown that benzene oxide/oxepin photolyzes in sunlight to give phenol with a yield of 43.2 + 4.5%. This reaction mechanism is therefore feasible for the formation of phenol in the benzene-OH reaction. However, photolysis of toluene l,2-oxide/2-methyloxepin gave o-cresol only in small yields, 2.7 + 2.2% (Klotz et al., 1998) this suggests that cresols formed in the OH-toluene reaction come primarily from the direct reaction (63) of the OH adduct with 02, in contrast to the conclusions of Moschonas et al. (1999). 

The spontaneous oxepin-benzene oxide isomerization proceeds in accordance with the Woodward-Hoffmann rules of orbital symmetry control and may thus be classified as an allowed thermal disrotatory electrocyclic reaction. A considerable amount of structural information about both oxepin and benzene oxide has been obtained from theoretical calculations using ab initio SCF and semiempirical (MINDO/3) MO calculations (80JA1255). Thus the oxepin ring was predicted to be either a flattened boat structure (MINDO/3) or a planar ring (SCF), indicative of a very low barrier to interconversion between boat conformations. Both methods of calculation indicated that the benzene oxide tautomer... 

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). 

Kinetic data on the oxepin-benzene oxide equilibration have been obtained from the temperature-dependent NMR studies. Low values were observed for the enthalpy of isomerization of oxepin (7.1 kJ mol-1) and 2-methyloxepin (1.7 kJ mol-1) to the corresponding benzene oxides (67AG(E)385). The relatively small increase in entropy associated with oxepin formation (5-11 J K 1 mol-1) is as anticipated for a boat conformation in a rapid state of ring inversion. Thermal racemization studies of chrysene 1,2- and 3,4-oxides have allowed accurate thermodynamic parameters for the oxepin-arene oxide equilibration process in the PAH series to be obtained (81CC838). The results obtained from racemization of the 1,2- (Ea 103.7 kJ mol-1, AS 3.7 JK-1 mol-1 and 3,4- (Ea 105.3 kJmoF1, AS 0.7 J K"1 mol ) arene oxides of chrysene are as anticipated for the intermediacy of the oxepins (31) and (32) respectively. 

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 arene oxide valence tautomer of oxepins in principle should undergo nucleophilic substitution reactions (Sn2) which are characteristic of simple epoxides. In reality oxepin-benzene oxide (7) is resistant to attack by hard nucleophiles such as OH-, H20, NH2- and RNH2. Attempts to obtain quantitative data on the relative rates of attack of nucleophiles on (7) in aqueous solution hqye been thwarted by competition from the dominant aromatization reaction. 

O ) By formation of seven-from three-membered rings This is the most widely used synthetic route to monocyclic oxepins. The key step in the synthesis of oxepin-benzene oxide (7) is the dehydrohalogenation of a dibromoepoxide precursor (64AG(E)S10). Since the benzene oxide valence tautomer is formed initially the valence tautomerization of the latter to oxepin (equation 51) may be considered as a ring expansion reaction. 

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... 

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... 

Information on the site of attack by the organometallic reagents on 86 was obtained, using the reaction of benzene oxide-oxepin-3,6-D2. Methyllithium produced cis-(230) by exclusive 1,6-addition. Analysis of the cis alcohol obtained from the reaction of dimethylmagnesium shows it to be ds-(230) resulting from substitution at the 3-carbon atom, whereas frans-(230) is formed directly by trans 1,2-addition. Methyllithium, by contrast, leads only to 1,2-trans product 231 with 45. 

Valence tautomers, benzene oxide 1 and oxepine 2 (Equation 1), as well as relative tautomeric systems, benzene sulfide-thiepine and o-xylene-2,7-dimethyloxepine, have been studied by a post-Hartree-Fock (HF) ab initio QCISD(r)/6-31G //MP2/6-31G method. In particular, the enthalpy calculated for a benzene oxide-oxepine system is 0.59 kj moF1 <1997PCA3371>. The calculated molecular orbital (MO) energies are in linear relationship to those from the photoelectron (PE) spectra <1996JCF1447>. Barrier to tautomerization for a benzene oxide-oxepine system is 29.4 kj mol-1. Protonation stabilizes the oxide form versus the oxepine <1997PCA3371>. 

By H NMR monitoring of the oxidation of benzene oxide-oxepine with dimethyldioxirane (DMDO), a significant by-product, oxepine 4,5-dioxide, was identified <1997CRT1314>. This fact supports the hypothesis that the route from oxepine to muconaldehyde proceeds via oxepine 2,3-oxide with a minor pathway leading to symmetrical oxepine 4,5-oxide. The DMDO oxidations provide model systems for the cytochrome P450-dependent metabolism of benzene and atmospheric photooxidation of benzenoid hydrocarbons. 

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. 

Additional evidence for the rapid equilibration in the benzene oxide-oxepin system la-lb has accrued from a range of molecular orbital (MO) calculations. ... 

The most general synthetic route to benzene oxides-oxepins is that initially developed by Vogel for 1. 1,4-cyclohexadienes (readily available from [2+4] cycloaddition of alkynes and butadienes, lithium-ammonia reduction of arenes, or dehydration of cyclohexenols) were converted to dibromoepoxides, the immediate precursors of benzene oxides. Modifications of this route have been used to prepare Ic and Id. Treatment of the monosubstituted arene oxide 43 (Figure 3) with (Et)4NF or thermal isomerization of 3-oxaquadricyclane provide additional synthetic routes to la. Similarly, the thermal (or photochemical) isomerization of the monoepoxide of Dewar benzene yielded la. ... 

P(0)(0Me)2] gives the pyrans 65a-b and the diazepines 67a-b. Diazepines 67a-b are formed by spontaneous isomerization of the intermediate 2-(diazomethyl)-2//-pyrans 66a-b (87JOC3851). In contrast, the analogous reactions of 4-methyl-2,6-diphenylpyrylium tetrafluoroborate 63b with 64a-b give only 68a-b. The allylpalladium chloride-catalyzed decomposition of 65a-b and 68a-b in benzene solution gives 92-98% of oxepines 69a-b,d. Oxepines 69a-b,d react with triazolinedione 55 to form the Diels-Alder adducts 70a-b,d (83-89%), which are derived from the valence tautomeric benzene oxides. The corresponding reaction of 69c with 55 under otherwise identical conditions proceeds differently in that an isomer with structure 70 c (66%) is formed along with 70c (23%). 

Recently Paquette367 reviewed the physical data on azepines, oxepins, and thiepins and discussed concisely the question of antiaromaticity in these systems. In short, the rings may suffer antiaromatic destabilization if they assume a planar conformation, a conformation which may also be destabilized by ring strain, X-Ray data for 141368 and kinetic data derived from variable-temperature NMR studies on benzene oxide = oxepin (142 ) 369 equilibria suggest that these rings exist in boat conformations (143). Recent X-ray analysis has revealed that the related diazepine (144) also exists in a boat conformation in the solid state.370... 

The reaction of oxepin (228 R = H) was complicated by the simultaneous photochemical reaction of benzene oxide, the valence isomer of oxepin.26 The results varied with solvent, temperature, and wavelength.269 The reaction proceeded with high selectivity to 2-oxa-bicyclo[3.2.0]hepta-3,6-diene (229 R = H) upon irradiation (A >310 nm) at room temperature. In most other cases the reaction was attended with the formation of phenol, probably from benzene oxide via Dewar benzene oxide, as this compound is known to isomerize photo-... 

The synthesis of monocyclic oxepins starts from 3,4-dibromo-7-oxabicyclo[4.1.0]heptanes 12, which are readily accessible from cyclohexa-1,4-dienes by monoepoxidation providing 13, followed by bromine addition to the remaining double bond. A double dehydrobromination of 12 with methoxide or DBU yields the benzene oxide/oxepin ... 

The transformation of benzvalene into oxepin-benzene oxide tautomeric system <84CB2963> is another example of oxepin formation from five-membered rings. 

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