Oxepines, formation

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. 

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>. 

Oxepin formation.1 A 1-1. three-necked flask fitted with a stirrer and thermometer and connected by means of a section of Gooch rubber tubing to a 125-ml. Erlenmeyer flask containing 33.2 g. of potassium /-butoxide (MSA Research Corp.) is charged with 42.1 g. of 4,5-dibromo-l,2-dimethyl-1,2-epoxycyclo-hexane (1) in 500 ml. of ether and cooled to 0°. The potassium /-butoxide is added... 

Oxepins. - Formation. The tetrahydro-oxepin derivatives (129) and (130), notable as the first heterocyclic rrans-cycloheptenes, have been synthesized via decomposition of the diazonium ion (128). They rearranged slowly to the ds-isomers at room temperature but could readily be trapped as Diels-Alder adducts with 2,3-dimethylbuta-l,3-diene. ... 

The spontaneous oxepin-benzene oxide isomerization proceeds as a thermally allowed, disrotatory process according to the Woodward-Hoffmann rules. Because of eclipsing interactions, 2,7-substituents destabilize the benzene oxide structure and favour oxepin formation. If the 2,7-positions are bridged, the size of the bridge influences the oxepin-benzene oxide equilibrium. This is shown by studies of the 2,7-methylene-bridged systems 7 and 8 If n = 3, only the indane oxide is present if n = 4, tetrahydronaphthalene oxide predominates in the equilibrium mixture if n = 5, oxepin and benzene oxide are present in a ratio of 1 1 [4]. 

Oxepins.—Formation. A new route to benzoxepins from (Z)-styryl-oxirans, e.g. of (119) from (117), is of the same general type as the route to benzodiazepines from diazoalkanes [(49) (50), described above]. Thermal cleavage of the... 

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

The thiepin system 31 is formed quantitatively by ring expansion of the diazoacetate derivative 30 via carbene formation catalyzed by 7r-allylpalladium chloride and its intramolecular insertion[31], The 4-diazomethyl-4//-pyrane 32 is expanded to the oxepine 33 in quantitative yield with the same catalyst[32]. 

Apparent nucleophilic attack on large, fully unsaturated rings may occur by way of attack on a valence tautomer, such as the reaction of oxepin with azide ion. Attack on the oxanorcaradiene valence tautomer leads to ring opening of the three-membered ring, and formation of 5-azido-6-hydroxy-l,3-cyclohexadiene (Section 5.17.2.2.4). 

Oxepin, 2-acetoxy-2,3,4,5-tetrahydro-thermal reactions, 7, 559 Oxepin, 3-chloro-synthesis, 3, 725 Oxepin, 2,3-dihydro-cycloaddition reactions, 7, 563 nucleophilic reactions, 7, 562 reduction, 7, 563 Oxepin, 2,5-dihydro-synthesis, 7, 578, 580 Oxepin, 4,5-dihydro-formation, 7, 579 reduction, 7, 563 synthesis, 7, 579 Oxepin, 2,7-dimethyl-NMR, 7, 552... 

Thermolyses of 3-oxaquadricyclanes with different substituents at C1(C5) and C6(C7) such as carboxy and phenyl groups showed that the reaction generally gives oxepins with the carboxy functions in the 4- and 5-position.24 This is also true when the substituents in the 6- and 7-positions form a bridge of six carbon atoms, e.g. formation of 9.129131 The rearrangement of these 3-oxaquadricyclanes gives access to the [6]paracyclophane system. 

Attempts have been made to catalyze the arrangement of 3-oxaquadricyclane to oxepins with transition-metal complexes.1 32 1 35 When dimethyl 2,4-dimethyl-3-oxaquadricyclane-l,5-dicarboxylate is treated with bis(benzonitrile)dichloroplatinum(II) or dicarbonylrhodium chloride dimer, an oxepin with a substitution pattern different from that following thermolysis is obtained as the main product. Instead of dimethyl 2,7-dimethyloxepin-4,5-dicarboxylate, the product of the thermal isomerization, dimethyl 2,5-dimethyloxepin-3,4-dicarboxylate (12), is formed due to the cleavage of a C O bond. This transition metal catalyzed cleavage accounts also for the formation of a 6-hydroxyfulvene [(cyclopentadienylidene)methanol] derivative (10-15%) and a substituted phenol (2-6%) as minor products.135 The proportion of reaction products is dependent on solvent, catalyst, and temperature. 

Diazomethanc undergoes addition of xanthylium perchlorate to afford dibenz[6,/]oxepin (4).193 The formation of this product can be rationalized by a carbenium ion that undergoes a Wagner Meerwein rearrangement. 

In a similar fashion, 9-(a-hydroxybenzyl)xanthene is converted to 10-phenyldibenz[b,/]oxepin (6) by treatment with p-toluenesulfonic acid in formic acid.196 Substituents in one of the benzene rings can give rise to the formation of two different products. In this study,196 the location... 

Numerous reactions have been described in which the oxygen of the oxepin system is removed to give benzene derivatives. The formation of the aromatic products can be rationalized by an arene oxide as intermediate. A suitable reagent for the elimination of an oxygen atom from this heterocycle is triphenylphosphane, e.g. formation of l,24 2a,12 and 2b.1,9... 

When the valence tautomeric mixture of oxepin and benzene oxide is treated with singlet oxygen, the primary product is the 1,4-endoperoxide 3 which has proven to be too labile for isolation.219 Its formation can be rationalized by a 1,4-addition across the diene system of the benzene oxide structure 3 then rearranges to ba s-3,6,9-trioxatetracyclo[6.1.0.02 4.05 ]nonane (transbenzene trioxide, 4). 

Occasionally, addition products of 4//-l,2,4-triazole-3,5-diones or diazenedicarboxylic esters and oxepins have been obtained whose formation can be rationalized by an addition to the 2,4-diene system in the oxepin, e.g. formation of 10.190191 In these cases, the primary adduct usually cannot be isolated, because it undergoes a hetero-Cope rearrangement to a tricyclic or bicyclic structure in which the oxepin oxygen has become part of a carbonyl function.190 191,227... 

The reaction of oxepin with dimethyl l,2,4,5-tetrazine-3,6-dicarboxylate affords a 2 1 mixture of products 9 a and 10, whose formation can be rationalized by a [4+2] and a [4 + 6] cycloaddition, followed by nitrogen extrusion.235 With 2,7-dimethyloxepin, only dimethyl 6,8-dime-thy 1-2.4a-dihydrooxepino[4,5-c/]pyridazine-l,4-dicarboxy late (9b) as product of the [4 + 2] cycloaddition can be isolated.235 236... 

The bicyclic oxepin 8//-3-oxacyclohept[d]oxepin-8-one dissolved in trifluoroacetic acid undergoes a rearrangement to the expected phenol derivative 1. Substituents in the 2- and/or 7-position of the oxepin part, however, give rise to the formation of l-acylazulen-6-ols 2 by ring contraction.148 The 2,7-diphenyl derivative affords a mixture of l-benzoyl-2-phenylazulen-6-ol (37%), l-benzoyl-2-phenylazulen-6(l//)-one (35%), and 2-phenylazulen-6-ol (23%), which was presumably formed via the azulenone and a shift of the benzoyl substituent to the oxygen. 

The light-induced reaction of pentacarbonyliron with oxepin or 2,7-dimethyloxepin results in the formation of small quantities (3-5 %) of a tricarbonyliron complex of the seven-mem-bered heterocycle.253,251 The main products are benzene (o-xylene) and phenol (2,6-dimethyl-phenol). When 1-benzoxepin is treated with pentacarbonyliron, the tricarbonyliron complex is obtained in 22% yield.254... 

A precedent<42) for this type of reaction can be found in the formation of benz[/]oxepin (42) from the epoxide (41) ... 

The exclusive and quantitative formation of oxepins upon Pd-catalyzed decomposition of 4-diazomethyl-4-methyl-4 //-pyrans (Entry 11) contrasts with the results of the CuCl-promoted reaction which affords a 2 1 mixture of oxepin (by 1,2-C migration) and 4-methylene-4//-pyran (by 1,2-H migration) under otherwise identical conditions 381J. When the methyl group at C-4 of the diazo precursor is replaced by H, the metal-catalyzed route to thiepins is no longer viable Pd- or Cu(I)-catalyzed decomposition of 4-diazomethyl-4//-thiopyrans invariably leads to 4-methylene-4H-thiopyrans 378 (Entry 10). Only the proton-catalyzed decomposition of these diazo compounds affords the desired thiepin, albeit in low yield 378). 

Using the same rhodium catalyst, Brummond has also observed the formation of seven-membered ring products and applied to interesting syntheses of azepines and oxepines (Scheme 123). 

Like the cyclization of the parent system, the photocyclization of hetero analogues of norbornadiene was reported many years ago. Recent interest in this area will serve to illustrate the potential of the conversions. Thus the irradiation of the oxanorbomadiene system 259 brings about conversion to the oxepine 260138. The formation of 260 presumably arises by quadricyclane 261 formation, followed by secondary photolytic ring-opening. Other research has shown that irradiation of the oxanorbomadiene 262 follows the same reaction mode and it undergoes (2 + 2)-cycloaddition to the quadricyclane derivative 263. Apparently, in this instance, cycloreversion affords the ylide 264 that can be trapped by suitable addends, giving the adducts illustrated in Scheme 3139. 

In general, this approach can be represented by equations 207 and 208 wherein the formation of cis- and fraws-substituted seven-membered rings (e.g. tropones or oxepines) is controlled by selection of appropriate isomeric divinylcyclopropanes or divinylepoxides as precursors. We will discuss here a series of examples which are not covered by a recent review260. 

The synthesis of these rings involves annulation of the furan ring onto the preformed benzoxepine core or intramolecular oxepine C-C bond formation of the furan precursors. Thus, 2-methyldibenzo[ 7,/]furo[2,3-d]oxepines 148 (R = H, Cl)... 

The next two examples illustrate intramolecular oxepine C-C bond formation of the furan precursors. Palladium catalyzed intramolecular arylation of 153... 

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