Phenanthrene oxides

Ridder, L. Rietjens, I.M. Vervoort, J.A. Mulholland, A., Quantum mechani-cal/molecular mechanical free energy simulations of the glutathione S-transferase (Ml-1) reaction with phenanthrene 9,10-oxide, J. Am. Chem. Soc. 2002,123, 9926-9936. 

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-... 

Turning to enzymatic hydration, we see from the data in Table 10.1 that phenanthrene 9,10-oxide Fig. 10.10, 10.29) is an excellent substrate for epoxide hydrolase. Comparison of enzymatic hydration of the three isomeric phenanthrene oxides shows that the Vmax with the 9,10-oxide is greater than with the 1,2- or the 3,4-oxide the affinity was higher as well, as assessed by the tenfold lower Km value [90]. Furthermore, phenanthrene 9,10-oxide has a plane of symmetry and is, thus, an achiral molecule, but hydration gives rise to a chiral metabolite with high product enantioselectivity. Indeed, nucleophilic attack by epoxide hydrolase occurs at C(9) with inversion of configuration i.e., from below the oxirane ring as shown in Fig. 10.10) to yield the C-H9.S, 10.S )-9,10-dihydro-9,10-diol (10.30) [91],... 

A peculiar reduction occurred on treatment of a dialdehyde, diphenyl-2,2 -dicarboxaldehyde, with tris(dimethylamino)phosphine at room temperature phenanthrene-9,10-oxide was formed in 81-89% yield [302],... 

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). 

ARENE OXIDE SYNTHESIS PHENANTHRENE 9,10-OXIDE (Phenanthro[9,10-ft]oxirene, 10,9 A-dihydro)... 

Phenanthrene-9,10-oxide (2) Phenanthrene, 9,10-epoxy-9,10-dihydro- (8) Phenanthro[9,10-fe]oxirene, la,9b-dihydro- (9) (585-08-0)... 

Nitrogen heterocycles continue to be valuable reagents and provide new synthetic approaches such as NITRONES FOR INTRAMOLECULAR -1,3 - DIPOLAR CYCLOADDITIONS HEXAHYDRO-1,3,3,6-TETRAMETHYL-2,l-BENZISOX AZOLINE. Substituting on a pyrrolidine can be accomplished by using NUCLEOPHILIC a - sec - AM IN O ALKYL ATION 2-(DI-PHENYLHYDROXYMETHYL)PYRROLIDINE. Arene oxides have considerable importance for cancer studies, and the example ARENE OXIDE SYNTHESIS PHENANTHRENE 9,10-OXIDE has been included. An aromatic reaction illustrates RADICAL ANION ARYLATION DIETHYL PHENYLPHOSPHONATE. 

Epoxidation of aromatic hydrocarbons is an important method for the preparation of arene oxides. m-Chloroperbenzoic acid (MCPBA) is used in a two-phase system that involves treating the hydrocarbon with a large excess ( 10-fold) of MCPBA in methylene chloride-aqueous sodium bicarbonate at room temperature. The yields are moderate (10-60%). Because the arene oxides are sensitive to acids, the presence of sodium bicarbonate buffer is necessary. A number of K-region (see Section VII for a definition) epoxides like phenanthrene 9,10-oxide (1, 59%), 9,10-dimethylphenanthrene 9,10-oxide (2,40%), 9-phenylphenanthrene 9,10-epoxide (3,50%), pyrene 4,5-oxide (4, 14%), and chrysene 4,5-oxide (5,9%) have been prepared by this method.9... 

This method was used to convert phenanthrene-9,10-oxide into the 9,10-imine in 72% yield. This imine is thermally stable at temperatures up to 190°. 

In general, K-region arene oxides behave rather like aliphatic epoxides and thus readily undergo hydration reactions, whereas benzene oxides and non-K-region arene oxides form dihydrodiols much more reluctantly. Kinetic studies of the mechanism of solvolysis of phenanthrene 9,10-oxide 2 have been carried out in several laboratories.Below pH 7 the hydrolysis reaction was acid-catalyzed and the products included the trans- and c/s-9,10-dihydrodiols along with a preponderance of 9-phenanthrol, while above pH 7 the reaction proceeded via the spontaneous mechanism ( o) mainly the frans-dihydrodiol. 

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