1.2- Naphthalene oxide

Like for benzene, the cytotoxicity of naphthalene is not due to the epoxide but to the quinone metabolites, namely 1,2-naphthoquinone and 1,4-naphthoquinone [85], As shown in Table 10.1, naphthalene 1,2-oxide (10.2) is a better substrate than benzene oxide for epoxide hydrolase. Its rapid isomerization to naphthalen-l-ol, facile enzymatic hydration to the dihydrodiol and lack of reactivity toward nucleophiles such as glutathione may explain its absence of direct toxicity [85],... 

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). 

In the aromatic-ring-annelated oxepin series the resonance effect is clearly the major influence dominating other factors (e.g. temperature, solvent, etc.) which affect the oxepin-arene oxide equilibrium. It is however very difficult to exclude the presence of a minor (spectroscopically undetectable) contribution from either tautomer at equilibrium. This problem has been investigated by the synthesis of chiral arene oxides from polycyclic aromatic hydrocarbons (PAHs). The presence of oxepin (26) in equilibrium with naphthalene 1,2-oxide has been excluded by the synthesis of the optically active arene oxide which showed no evidence of racemization in solution at ambient temperature via the achiral oxepin (26) <79JCS(Pl)2437>. 

Figure 4.60 Conjugation of naphthalene-1,2-oxide with glutathione and formation of naphthalene mercapturic acid.

Naphthalene-3,6-disulfonic acid, l,8-dihydroxy-2-(2-thiazolylazo)-analytical uses, 6, 328 Naphthalenes 1,2-oxide... 

Naphthalene 1,2-oxide (45) can be prepared by treatment of bromohydrin 46 with sodium methoxide in THF. Cyclization and dehydrobromination are achieved in a single pot.28 By this method, the non-K-region epoxide phenanthrene 1,2-oxide (47) and the bay-region oxide phenanthrene 3,4-oxide (48) have also been prepared.28 The syntheses of homobenzene analog 49 and... 

The photooxide of naphthalene (74) on treatment with triphenylphosphine is converted to naphthalene 1,2-oxide (45).40 The photooxide of anthracene (75) is converted to syw-anthracene[4a,10 9,9a]diepoxide (76) in 78% yield by means of an interesting photochemical rearrangement.41 The endoperoxide of... 

Naphthalene 1,2-oxide (45) has been obtained by bromination (NBS)-dehydrobromination (DBN) of tetralin 1,2-epoxide (115).57 Sodium in liquid ammonia gives diepoxide 116 from 117.58 Also, the saturated compound 118 with potassium f-butoxide in THF yields the oxaazabis-6-homobenzene system (119, 80%).29... 

Naphthalene 1,2-oxide (136), a non-K-region epoxide, shows low thermal stability. Anthracene 1,2-oxide, on the other hand, is stable at ambient temperatures for several weeks. Preparation of (+ )-(lR,2S)-anthracene 1,2-oxide (137), using the above method, constitutes the first example of preparation of an optically pure arene oxide. However, the non-K-region oxides of phenanthrene, namely, its 1,2- and 3,4-oxides (47 and 48), obtained from chiral precursors, racemize fast.66 Perturbational molecular orbital calculations indicate that epoxide-oxepin valence tautomerism is possible. However, the oxepin could not be detected by NMR. 

The mechanism of the NIH shift was not clearly understood until naphthalene 1,2-oxide (197) was isolated in the metabolism of 1-T-naphthalene (198) with hepatic monoxygenases the oxide then rearranges to 1-naphthol with migration of tritium from the 1- to the 2-position.112,113... 

Studies on the isomerization of 1-D- and 2-D-naphthalene 1-2-oxides (40 and 41, respectively) have been particularly informative133 (Table IX). 

With 1-D-naphthalene 1,2-oxide (210), the loss of deuterium depends only on the extent of the elimination of the proton, whereas with 2-D-naphthalene 1,2-oxide (211) the elimination reaction will not lead to any loss of D. From the table it can be seen that at low pH, elimination becomes important and competitive with retention. Above pH 7 the extent of elimination becomes insignificant... 

The photochemical reaction of non-K-region oxides like dideuterated benzene oxide (303) and naphthalene 1,2-oxide has been studied at room temperature and at 77 K in acetone. When D-(303) is irradiated in acetone at room temperature, products corresponding to migration of the oxirane ring to the next position are obtained. 

Naphthalene-1,2-oxide is a metabolic intermediate in the oxidation of naphthalene mediated by cytochrome P-450. 

Naphthalene 1,2-oxide. Yagi and Jerina have reported a new method for synthesis of arene oxides. The starting material for the preparation of naphthalene 1,2-oxide (5) is I-hydroxy-2-bromotetralin, (I), which is acetylated with irifluoroacctic anhydride in chloroform to give (2) in 84 % yield. This is converted into the dibromide (3) by treatment with NBS (note that tetralin 1,2-epoxidc is uiLstable to bromination with NBS). The... 

MF.THYLTHIOMETHYL ESTERS Chlo-romcthyl methyl sulfide. MONOBROMOCYCLOPROPANES Sodium bistrimcthylsilylamide. NAPHTHALENE 1,2-oxide ... 

Reactions of peroxides with triphenylphosphine usually result in monodeoxygenation. Dialkyl peroxides react relatively slowly with triphenylphosphine and give ethers as the major products for example, di-f-butyl peroxide gave di-f-butyl ether (81%) after being heated with triphenylphosphine at 110-120 C for 30 h. The mechanism suggested for these reactions is an ionic one, triphenylphosphine acting as a nucleophile. The reaction illustrated in Scheme 29 can then be rationalized by the loss of triphenylphosphine oxide and intramolecular attack on the double bond. The reaction has found several useful applications in synthesis an example is a preparation of naphthalene 1,2-oxide (Scheme 32). 

In addition to the temperature, solvent, and substituent effects, a preference for either the arene oxide or oxepin form may be achieved by localization of one double bond as part of an aromatic ring system. Thus the reluctance to form a cyclobutadiene ring causes 10 to exist preponderantly as its oxide form. Naphthalene 1,2-oxide 11 is the simplest arene-oxide member in the polycyclic aromatic hydrocarbon (PAH) series and exists exclusively in that tautomeric form. In contrast, naphthalene 2,3-oxide exists exclusively as the oxepin form 12 since the C4-CS bond in the oxepin ring forms part of an aromatic ring. ... 

The direct oxidation of PAHs as a synthetic route has been confined mainly to the more stable K-region arene oxides. However, the first isolation of an arene oxide resulting from direct chemical oxidation of a PAH (and to date the only example of a non-K-region arene-oxide synthesis by this route) was achieved in low yield by photolysis of pyridine A -oxide in the presence of naphthalene to form naphthalene 1,2-oxide 11. The relative susceptibility of non-K-region arene oxides to further epoxidation is one of the reasons for the lack of generality of this approach. 

The use of DBN made possible for the first time the synthesis of naphthalene-1,2-oxide (4) from 4-bromo-l,2-epoxy-l,2,3,4-tetrahydronaphthalene (3) ... 

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