Isomerization arene oxide-oxepin

Fig. 10.2. The arene oxide-oxepin isomerization, which may lead to racemization in certain...

The oxepin ring structure (8) appeared to be formed in preference to the arene oxide tautomer according to the NMR spectrum, and the oxepin form was unequivocally established by X-ray structure analysis (78AG(E)12l). Unfortunately the molecular dimensions of the oxepin ring in structure (8) were not included in the original report. In contrast, the valence isomeric arene oxide form of oxepin (9) was found to predominate and detailed information about the arene oxide molecular geometry was provided by the X-ray diffraction method (Table 3) (80LA1889). 

Another isomerization reaction of arene oxides is equilibrium with oxe-pins [5], Here, the fused six-membered carbocycle and three-membered oxirane merge to form a seven-membered heterocycle, as shown in Fig. 10.2. An extensive computational and experimental study involving 75 epoxides of monocyclic, bicyclic, and polycyclic aromatic hydrocarbons has revealed much information on the structural factors that influence the reaction rate and position of equilibrium [11], Thus, some compounds were stable as oxepins (e.g., naphthalene 2,3-oxide), while others exhibited a balanced equilibrium... 

The preference of 2,7-disubstituted oxepins for this tautomeric form at equilibrium may be rationalized in terms of a steric substituent effect. The eclipsing interactions of the 2,7-substituents in the arene oxide form will be diminished by isomerization to the oxepin. When the 2,7-substituents form part of an annelated ring system, e.g. (22)-(24), the tautomeric preference will be determined by the size of the methylene bridge (67AG(E)385). Thus when n = 5 the annelated oxepin (24) was present in approximately equal proportions with the arene oxide form. However with n =4. (23) tetralin 9,10-oxide was dominant. The... 

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. 

The protonation of oxepins-arene oxides at the ring oxygen atom and subsequent acid-catalyzed isomerization are very dependent upon the nature of substituents on the ring. This is exemplified by a comparison of the relative stabilities of oxepin (7) and oxepin-2,7-dicarboxylic acid (18) under acid conditions. Thus oxepin (7) spontaneously decomposed on clean glassware at ambient temperature (unless prewashed with base) while (18) showed no change over a period of 10 days in trifluoroacetic acid (79JA2470). 

The NIH shift has been found to occur during aromatic hydroxylations catalyzed by enzymes present in plants, animals, fungi and bacteria. It is thus evident that the acid catalyzed (or spontaneous) isomerization of oxepins-arene oxides is a very important type of in vivo reaction. It should be emphasized that the NIH shift may occur under either acid-catalyzed or neutral (spontaneous) conditions (76ACR378). The direct chemical oxidation of aromatic rings has also yielded both phenols (obtained via the NIH shift) and arene oxides (80JCS(P1)1693>. 

A similar solvent trapping mechanism has been proposed to account for formation of 5-indanol from acid-catalyzed isomerization of the arene oxide tautomer of oxepin (22) (73JA60641). 

As stated in Section 5.17.1.4, simple thiepins (e.g. 44) are generally too reactive to be isolable under ambient conditions. Thiepins (49), (50) and (51) are among the relatively few stable monocyclic thiepins to have been reported and the majority of reactivity studies on thiepins have been carried out on polycyclic thiepins. The chemical reactivity of thiepins can be considered separately from the reactivity of the valence tautomeric thianorcaradienes more readily than was the case for oxepins-arene oxides. A spontaneous thermal extrusion of sulfur appears to occur from the episulfide tautomer of thiepins and the stable thiepins (49)-(51) would thus appear to exist exclusively in this valence isomeric form. 

The oxepins (7 equation 54) and (92 equation 55) resulted from the spontaneous isomerization of their valence tautomeric arene oxide forms which were produced by photorearrangement of 2,3-epoxybicyclo[2.2.0]hex-5-ene (67JA3922) and phenanthrene 9,10-oxide (91) (73CC37) respectively. A rather specific synthetic route to the relatively stable oxepins (180)-(182) was based upon the acid-catalyzed dehydration and ring expansion of 2,6-di-r-butylcyclohexadiene-l,4-diols (Scheme 34) <71AG(E)425,71TL1257). 

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. ... 

Arene oxides show the characteristic reactions of epoxides (isomerization to ketones, reductions to alcohols, nucleophilic additions, deoxygenations) and olefins or conjugated dienes (catalytic hydrogenation, photochemical isomerization, cycloaddition, epoxidation, metal complexation). Where a spontaneous, rapid equilibration between the arene oxide and oxepin forms exists, reactivity typical of a conjugated triene is also found. 

Oxepins and their bicyclic valence tautomers, arene oxides are discussed in <95CHE(42)197>. Particularly noteworthy is the synthesis of a stable benzene oxide (63) which surprisingly shows little tendency to isomerize to the corresponding oxepin (64) in spite of the expectation that the fluorines would greatly destabilize the three-membered ring in the bicyclic structure (63) (Scheme 10) <90JA6715>. 

A completely novel preparation of alkylidene oxepines has been provided by Bourelle-Wargrier et who studied the gas- and liquid-phase thermolyses of the ethynyl vinyl oxiranes (403). Ethynyl cyclopropyl ketones such as (404) were the sole product in the gas phase, but these rearranged further in the liquid phase to the isomeric dihydro-oxepins (405) and (406). A trace of phenolic products was thought to have arisen from arene-oxides in equilibrium with the oxepines. 

Acid-catalyzed isomerization of 2,7-disubstituted oxepins 404 leads to products 407 and 408, depending on the nature of the substituent (equation 190). It was found that the oxepin valence tautomer 404 is more stable than the oxide valence tautomer 405 in 1,2-disubstituted arene 1,2-oxides. The isomerization proceeds via the so-called NIH shift (NIH = National Institute of Health, Bethesda, MD, USA) which involves the migration of the R substituent in the intermediate cation 406 to either of the adjacent carbon atoms to form the products 407 and 408. 

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