Arene oxides from phenanthrene

Detailed kinetic studies comparing the chemical reactivity ofK-region vs. non-K-region arene oxides have yielded important information. In aqueous solution, the non-K-region epoxides of phenanthrene (the 1,2-oxide and 3,4-oxides) yielded exclusively phenols (the 1-phenol and 4-phenol, respectively, as major products) in an acid-catalyzed reaction, as do epoxides of lower arenes (Fig. 10.1). In contrast, the K-region epoxide (i.e., phenanthrene 9,10-oxide 10.29) gave at pH < 7 the 9-phenol and the 9,10-dihydro-9,10-diol (predominantly trans) in a ratio of ca. 3 1. Under these conditions, the formation of this dihydrodiol was found to result from trapping of the carbonium ion by H20 (Fig. 10.11, Pathway a). At pH > 9, the product formed was nearly ex-... 

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 first arene oxides to be synthesized (1964) were obtained by the cyclization of appropriate seco derivatives. 0,0-Diformylbiphenyl derivatives, when treated with Mark s reagent [tris(dimethylamino)phosphine], gave arene oxides [Eq. (3)]. Thus K-region epoxides from phenanthrene and its analogs, benz[a]anthracene and its 7,12-dimethyl analog, have been prepared.34... 

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. 

Comparison of the reactivities of benzene oxides, naphthalene oxides, phenanthrene oxides, and arene oxides derived from benzo [a] pyrene and 7,12-dimethylbenz[a] anthracene with hepatic glutathione S-epoxide transferase showed that benzene oxides without electron-withdrawing groups are poor substrates as also are polycyclic arene oxides. Only naphthalene oxide was a good substrate. 

Reactions of K-region arene oxides derived from phenanthrene and 7,12-dimethylbenz[a] anthracene with nucleosides have been studied with a view to assessing the carcinogenicity of the products obtained.199... 

A number of K-region arene oxides have been detected as intermediates in the metabolism of the corresponding PAHs in liver systems for example, phenanthrene, benz[a]anthracene, pyrene, benzo [a]pyrene, and dibenz(a,h)anthracene. These K-region arene-oxide metabolites were generally only detected by trapping the radiolabeled intermediate. The arene-oxide metabolite 102 obtained from a-naphthoflavone was found to be sufficiently stable with respect to isomerization and resistant to attack by epoxide hydrolase so that it could be isolated and identified spectroscopically. ... 

In an attempt to determine the atmospheric oxidation processes that would result in an arene oxide functional group in PAHs, Murray and Kong (1994) studied the reaction of particle-bound PAHs with oxidants derived from the reactions of ozone with alkenes. Phenanthrene and pyrene were converted to arene oxides under these simulated atmospheric conditions. Control experiments indicated that the oxidant responsible for the transformation was not ozone, but a product of the reaction of ozone with tetramethylethylene (TME), probably the carbonyl oxide or the dioxirane derived from TME. 

Three arene oxides can be obtained from phenanthrene. 

Epoxidation of Arenes. Certain arenes (acenaphthylene, phenanthrene, and pyrene) are readily oxidized to the corresponding arene oxides by the peroxy intermediate (1) generated from sulfonyl chloride (3) in polar aprotic solvents such as MeCN and DME. Superoxide (4) is a strong base and reactions with (1) take place under mild and basic conditions. Acenaphthylene oxide (10) is unstable under acidic conditions but is more stable under basic conditions. Oxide (10) was obtained in 95% yield. ... 

Figure 7.7 Phenanthrene is metabolized to a relatively stable arene oxide at its 9-and 10-positions. The stability arises from the fact that the compound still has two intact aromatic rings. The long half-life of the oxide allows time for alternative chemistry to occur. Here, epoxide hydrolase catalyzes the opening of the epoxide to form a trans-dihydrodiol.This is no longer electrophilic and poses little hazard to cells. The hydroxyl groups provide a handle for attachment of glucuronic acid, which dramatically increases the water solubility of the metabolite and allows for its elimination from the body by excretion in the urine.

Exposed multiple bonds of angular arenes are specifically prone to oxidation. The synthetic value of such double bonds arises from their high reactivity towards simple electrophiles, enophiles, and radicals. Heavy metal catalysis, periodate oxidation, and ozonolysis are the standard tools for oxidative bond cleavage in these substrates. For economic and ecological reasons, technically applicable alternatives are of great interest. Phenanthrene (29) represents a typical substrate... 

Arene dioxides. Arene dioxides have not been identified as metabolites of polycyclic arenes, but some identified metabolites may be formed from arene dioxides. Arene dioxides can be obtained by reaction of polyarenes containing a double bond comparable to the 9,10-double bond of phenanthrene (such as 2) by oxidation with dimethyldioxirane (1), but in modest yield. The dioxide S cannot be obtained by this method, but can be obtained via a tramwic-bromoacetate.1... 

There have been several recent investigations into the mechanism of photo-cyanation of aromatic hydrocarbons. The process with naphthalene, biphenyl, and phenanthrene has been subjected to a kinetic analysis the reactions in dry or aqueous methyl cyanide are shown to involve two transient species, the first of which is an ionic complex formed from a triplet excimer of the arene, or, in the presence of an electron acceptor, from a triplet exciplex. Reaction of the transient complex with the cyanide ion yields the radical ArHCN, and in aqueous methyl cyanide this second transient reacts with itself to produce dihydrocyano- and cyano-compounds. In dry methyl cyanide the radical species is oxidized to the cyano product. 

Z)-Diarylethenes, such as stilbene, also undergo a 671-electrocyclization reaction upon irradiation from the singlet n,n state, but not upon triplet sensitization.487 529,599 622 The photochemical orbital symmetry-allowed conrotatory closure leads to the trans-dihydro derivative 66 (Scheme 6.23), which can subsequently be oxidized by oxygen or iodine to the corresponding arene (phenanthrene) in nearly quantitative yield.561... 

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