2-Methyl oxepin

In the case of toluene, as shown in Reaction Scheme 7.10, three reaction pathways of hydroxymethyl cyclohexadienyl radical with O2 are conceived the formation of (1) cresol (B) by the H-atom abstraction from the OH-added carbon (pathway a), (2) toluene 1,2-epoxide (C) and the 2-methyl oxepin (D) equilibrated with it, and (3) hydroxymethyl cyclohexadienyl peroxy radical (E) formed by the O2 addition to the benzene ring (Suh et al. 2003 Cartas-Rosado and Castro 2007 Baltaretu et al. 2009). The formation of cresol by pathway (a) is well known, and o-cresol is produced predominantly followed by p- and m-cresol reflecting the ortho- and para-orientation of the OH addition to benzene ring (see Sect. 5.2.10). However, the ratio of the H-atom abstraction from the benzene ring of hydroxy... 

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). 

III-E-21. Benzene Oxide (Oxepin) and Toluene-1,2-Oxide (2-Methyl Oxepin)... 

For toluene-l,2-oxide/2-methyl oxepin, photolysis and OH reaction are again competing daytime losses (Klotz et al., 20(X)). The OH reaction is calculated to occur on a timescale of about 0.5 h, while the photolysis lifetime is about 40 min. with overhead Sun. Products of the OH-initiated oxidation are the E, E- and , Z- isomers of 6-oxohepta-2,4-dienal, analogous to the 2,4-hexadiendial products of the benzene oxide/oxepin case. The main photolysis product identified was o-cresol, albeit only in about 10% yield. The reaction with NO3 is also very rapid, and should this species be present at nighttime, its removal via reaction with NO3 would be expected to occur in less than 1 min. in heavily polluted conditions. 

Figure IX-L-3. Estimated photolysis frequencies for the photodecomposition (disappearance) of benzene oxide/oxepin (R = H heavy curve) and toluene oxide/2-methyl oxepin (R = CH3 light curve) at 0.5 km altitude as a function of solar zenith angle using the measured value of yXCsHfiOf/jXNO ) = (4.41 0.44) x 10 and j(CH3C6H50)/jr(N02) = (3.99 0.48) x together with 7(N02) values as calculated for clear tropospheric skies at an altitude of 0.5 km and with an overhead ozone column of 350 DU.

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... 

Oxepin-2-carboxylic acid, methyl ester H NMR, 7, 552 <79JA2470)... 

Oxepin, 4-ethoxycarbonyl-2,3,6,7-tetrahydro-synthesis, 7, 578 Oxepin, 2-methyl-enthalpy of isomerization, 7, 555 Oxepin, 2,3,4,5-tetrahydro-reduction, 7, 563 synthesis, 7, 578 Oxepin, 2,3,4,7-tetrahydro-synthesis, 7, 578 Oxepin, 2,3,6,7-tetrahydro-oxidation, 7, 563 reduction, 7, 563 Oxepin-2,6-dicarboxylic acid stability, 7, 565 Oxepinium ions synthesis, 7, 559 Oxepins, 7, 547-592 antiaromaticity, 4, 535 applications, 7, 590-591 aromatization, 7, 566 bond lengths and angles, 7, 550, 551 cycloaddition reactions, 7, 27, 569 deoxygenation, 7, 570 dipole moment, 7, 553 disubstituted synthesis, 7, 584... 

H-Pyran, 2-alkoxy-4-methyl-2,3-dihydro-conformation, 3, 630 4H-Pyran, 2-amino-IR spectra, 3, 593 synthesis, 3, 758 4H-Pyran, 4-benzylidene-synthesis, 3, 762 4H-Pyran, 2,3-dihydro-halogenation, 3, 723 hydroboration, 3, 723 oxepines from, 3, 725 oxidation, 3, 724 reactions, with acids, 3, 723 with carbenes, 3, 725 4H-Pyran, 5,6-dihydro-synthesis, 2, 91 4H-Pyran, 2,6-diphenyl-hydrogenation, 3, 777 4H-Pyran, 6-ethyl-3-vinyl-2,3-dihydro-reactions, with acids, 3, 723 4H-Pyran, 2-methoxy-synthesis, 3, 762 4H-Pyran, 2,4,4,6-tetramethyl-IR spectra, 3, 593 4H-Pyran, 2,4,6-triphenyl-IR spectra, 3, 593... 

An acetyl group in the 2-position favors the monocyclic structure presumably because of the resonance stabilization.12 The same observation was made with oxepin-2,7-dicarbaldehyde, oxepin-2,7-dicarboxylic acid, and oxepin-2,7-dicarbonitrile.23 Substituents in the 4- and 5-positions of the oxepin such as methyl or methoxycarbonyl groups shift the equilibrium towards the epoxide.12 24 Low temperature 1H NMR studies on 7-ethyloxepin-2-carbonitrile and ethyl 7-ethyloxepin-2-carboxylate established a nonplanar boat geometry with a ring-inversion harrier of 6.5 kcal mol-1.25... 

Treatment of the bis-ylide generated from bis 2-[(triphenylphosphonio)methyl]phenyl ether and sodium amide with oxygen gives dibenz[A./]oxepin (3) in 50% yield.98 99... 

The reaction of 2-nitrodibenz[6,/]oxepin-10-carboxylic acid with potassium dichromate in acetic acid takes a rather unexpected course 9-methyl-2-nitroxanthene (2) is formed by loss of the carboxylic group and ring contraction.107... 

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... 

Methyl-7-(trimethylsilyl)oxepin and 4-methyl-4//-l,2,4-triazole-3,5-dione as dienophile undergo a Diels-Alder reaction in which the 4,6-diene structure of the seven-membered ring react. Contrary to the aforementioned reactions, the primary adduct 12 is stable and does not rearrange to a carbonyl compound.222... 

Bromomethyl-3,4-dibromo-3,4-dihydrocoumarin 1 (Fig. 11.4) and its chloro-methylated analogue 2b rapidly and progressively inactivate a-chymotrypsin and also the activities of a series of trypsin-like proteases. A benzyl substituent characteristic of good substrates of a-chymotrypsin was introduced at the 3-position to make inhibition more selective. This substituted dihydrocoumarin 3 irreversibly inhibited a-chymotrypsin and other proteases. These functionalized six-membered aromatic lactones, and their five- and seven-membered counterparts, 3//-benzofuran-2-ones 2a26 and 4,5-dihydro-3//-benzo[b]oxepin-2-ones 2c,27 were the first efficient suicide inhibitors of serine proteases. Their postulated mechanism of action is shown in Scheme 11.2. 

Another photocyclization to a benzo[c]phenanthridine was reported (127). Oppenauer oxidation of ( )-ophiocarpine (92) with potassium fm-butoxide and benzophenone in dioxane effected C-6—N bond cleavage to afford the hydroxyisoquinoline 219 via berberinephenolbetaine (121) (Scheme 39). Although photolysis of 219 gave only the oxepine 221, that of its methyl ether 220 furnished directly norchelerythrine (222) through electrocyclization followed by spontaneous elimination of methanol. 

For the synthesis ofthiepins and oxepins, [(ri3-C3Hs)PdCl]2-catalyzed decomposition of 4-diazomethyl-4-methyl-4/f-thiopyrans 387) or -pyrans38] ) is the method of choice. Purely thermal decomposition of the former diazo compounds would require higher temperatures and thus would cause extrusion of sulfur from the primarily formed thiepin, yielding a benzene derivative. 

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). 

Hexamethylbenzene reacts with DMDO via three pathways (i) to an arene oxide, which rapidly rearranges to an oxepin tautomer that then is oxidized to a cw-diepoxide and then to a cis, cis,trans-triepoxide (ii) a methyl group migrates in the first epoxide to give a cyclohexadienone, which then reacts to give a frani -diepoxide (iii) C—H insertion to give the benzyl alcohol and then the corresponding benzoic acid. ... 

The 7-azaquadricyclane (77), like its precursor (12), shows evidence in the NMR spectrum of restricted rotation about the N-CO bond. All the 7-heteroquadricyclanes, 76-79, are thermolabile, and they rearrange very readily to the corresponding azepines (80) or oxepin (81). (In another instance the 7-oxabicyclo[4.1.0] valence-bond tautomer was obtained instead. ) In appropriate conditions the addition of acetylenic esters (methyl propiolate and dimethyl acetylene-dicarboxylate) competes successfully with the isomerization and gives the ca o-tricyclic adducts 82 or 83. " °... 

The nature and position of substituents relative to the ring oxygen atom have an important effect on the acid-catalyzed isomerization of oxepins. It has been observed that, in addition to the hydrogen isotopes ( H, 2H, 3H), chloro, bromo, methyl (72E1129) and alkoxycarbonyl (79JA2470) substituents also show the migration-retention sequence found in the NIH shift. 

Fully unsaturated seven-membered heterocyclics have alternating bond lengths and are normally in boat conformations. Ring inversion barriers are 42.7 kJ mol-1 for 3-methyl-3ff-azepine and 35.6 kJ mol-1 for 3//-azepin-2-one (CHEC 5.16.2.3). The barriers for oxepin and thiepin are somewhat lower. Annulation can introduce large conformational barriers, to the extent of making possible the resolution into enantiomers of a tribenzoxepin (71CB2923). 

For compound (151 R = Me or Ph), the base peak arises from an [M-HI]t ion. The molecular ion from the parent compound is not observed. Metastable ion peaks aided the elucidation of the fragmentation pathways which are outlined in Scheme 25. The [M—HI] ion (151a) may possess either a methylene pyran or an oxepin structure. Further decomposition of this ion occurs by loss of a hydrogen radical. Expulsion of a methyl radical from (151a) generates (151b) which decomposes as shown (Scheme 25). 

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