960-92-9Relevant academic research and scientific papers
The directed ortho metalation - Palladium catalyzed cross coupling connection. A general regiospecific route to 9-phenanthrols and phenanthrenes. Exploratory further metalation
Fu, Jian-Min,Snieckus, Victor
, p. 905 - 919 (2007/10/03)
A new general and regiospecific synthesis of 9-phenanthrols (1 + 2 → 3 → 4, Scheme 1, Table 1) proceeding by a Directed ortho Metalation (DoM), Suzuki-Miyaura crocs coupling, and a new LDA-mediated Directed remote Metalation sequence is described. The facile Pd-catalyzed hydrogenolysis of the phenanthrols 4 into the corresponding phenanthrenes 5 via their triflates 18 translates the original DoM regioselectivity also into a general synthesis of phenanthrenes (Table 2). Further DoM (19 → 20, 21; 24 → 25), cross coupling (20c → 23), as well as oxidation - ring contraction (4b, 4f → 28a, 28b) chemistry of phenanthrene derivatives is reported.
Influence of Na+ on DNA reactions with aromatic epoxides and diol epoxides: Evidence that DNA catalyzes the formation of benzo[a]pyrene and benz[a]anthracene adducts at intercalation sites
Fernando, Harshica,Huang, Chao-Ran,Milliman, Ann,Shu, Luchuan,LeBreton, Pierre R.
, p. 1391 - 1402 (2007/10/03)
Reactions of the benzo[a]pyrene (BP) and benz[a]anthracene (BA) metabolites, (±)-trans-7, 8-dihydroxy-anti-9, 10-epoxy-7, 8, 9, 10- tetrahydro-BP (BPDE), (±)-trans-3, 4-dihydroxy-anti-1, 2-epoxy-1, 2, 3, 4- tetrahydro-BA (BADE), (±)-BP-4, 5-oxide (BPO), and (±)-BA-5, 6-oxide (BAO), were examined under pseudo-first-order conditions at varying Na+ (2.0-100 mM) and native, calf thymus DNA (ctDNA) concentrations. In 0.2 mM ctDNA and 2.0 mM Na+, at a pH of 7.3, most BPDE, BADE, BPO, and BAO (87-95%) undergo DNA catalyzed hydrolysis or rearrangement. For BPDE and BPO, overall, pseudo- first-order rate constants, k, in 2.0 mM Na+ and 0.2 mM ctDNA are 21-72 times larger than values obtained without DNA. For BADE and BAO, the rate constants are less strongly influenced by DNA; k values in 0.2 mM ctDNA are only 9-12 times larger than values obtained without DNA. Kinetic data for BPDE, BPO, BADE, and BAO and DNA intercalation association constants (K(A)) for BP and BA diols which are model compounds indicate that K(A) values for BPDE and BPO in 2.0 mM Na+ are 6.6-59 times larger than those of BADE and BAO. The greater DNA enhancement of rate constants for BPDE and BPO, versus BADE and BAO, correlates with the larger K(A) values of the BP metabolites. DNA adducts, which account for less than 10% of the yields, also form. For BPDE in 0.20 mM ctDNA, k decreases 5.1 times as the Na+ concentration increases from 2.0 to 100 mM. Nevertheless, the DNA adduct level remains constant over the range of Na+ concentrations examined. These results provide evidence that, for BPDE in 0.20 mM DNA and 2.0 mM Na+, ctDNA adduct formation follows a mechanism which is similar to that for DNA catalyzed hydrolysis. The pseudo-first-order rate constant for adduct formation, k(Ad), given approximately by k(Ad) ? (k(cat, Ad)K(A)[DNA])/(1 + K(A)[DNA]), where k(cat, Ad) is a catalytic rate constant. For BADE, BPO, and BAO, the influence of varying DNA and Na+ concentrations on k values is similar to that for BPDE, and provides evidence that the formation of adducts follows the same rate law.
Acid-catalyzed rearrangement of K-region arene oxides: Observation of ketone intermediates and a sterically induced change in rate-determining step
Nashed, Nashaat T.,Sayer, Jane M.,Jerina, Donald M.
, p. 1723 - 1730 (2007/10/02)
K-region arene oxides rearrange to phenols in acetonitrile in two acid-catalyzed steps: rapid rearrangement of the arene oxide to positionally isomeric keto tautomers of K-region phenols, followed by slow enolization. Accumulation of the ketones, proposed intermediates in the acid-catalyzed solvolyses of arene oxides in aqueous solution, allowed their direct spectroscopic observation and characterization for the first time under solvolytic conditions. Rate constants and products are reported for the K-region arene oxides of benz[a]anthracene, its 1-, 4-, 7-, 11-, 12-methyl, and 7,12-dimethyl substituted derivatives, benzo[a]pyrene, benzo[c]phenanthrene, 3-bromophenanthrene, chrysene, dibenz[a,h]anthracene, phenanthrene, and pyrene. No primary kinetic isotope effect is observed for ketone formation from phenanthrene 9,10-oxide. A linear correlation with a slope of 1.07 is observed between the logarithm of the second-order rate constants for acid-catalyzed reaction of the arene oxide at each K-region position in acetonitrile (first step) and in methanol (where ketone does not accumulate). Negative deviations from this correlation are observed for the formation of ketones in which the carbonyl oxygen is peri to a methyl substituent. These results are discussed in terms of a mechanism in which pseudoaxial opening of the epoxide gives an initial carbocation that must undergo conformational isomerization in order to produce phenolic products by migration of a pseudoaxial hydrogen. For compounds that follow the correlation, the rate-determining step in both methanol and acetonitrile is formation of the carbocation. For those compounds that deviate from the correlation and whose carbocations have their hydroxyl group in a peri position to a methyl ring substituent, the rate-determining step changes from formation of the carbocation (methanol) to its conformational inversion (acetonitrile). With few exceptions, NMR and kinetic evidence show that the regioisomeric K-region keto tautomers from a given arene oxide enolize with very similar rates (kslow). Rates of enolization are decreased by electron withdrawing groups and by steric factors that favor nonplanarity of the ring system. A large primary kinetic isotope effect (kH/kD = 4.4) is observed for the acid-catalyzed enolization of the K-region ketone derived from phenanthrene. Slow abstraction of a proton by the solvent acetonitrile from the α-methylene group of the O-protonated ketone is proposed to account for these results and for the fact that ketone does not accumulate in more basic solvents. The major driving force for enolization (kslow) is development of aromaticity in the phenol. For unsubstituted keto tautomers, a linear relationship, log kslow = 31.8-39.2 (X), is observed, where X is the Hu?ckel π-bond character for the K-region bond of the parent hydrocarbon.
Solvolysis of K-region arene oxides: Substituent effects on reactions of benz[a]anthracene 5,6-oxide
Nashed, Nashaat T.,Balani, Suresh K.,Loncharich, Richard J.,Sayer, Jane M.,Shipley, David Y.,Mohan, Ram S.,Whalen, Dale L.,Jerina, Donald M.
, p. 3910 - 3919 (2007/10/02)
The solvolytic reactivity and products formed from benz[a]anthracene 5,6-oxide (BA-O) on substitution of a methyl group at positions 1 (1-MBA-O), 4 (4-MBA-O), 7 (7-MBA-O), 11 (11-MBA-O), and 12 (12-MBA-O), on 7,12-dimethyl substitution (7,12-DMBA-O), and on 7-bromo substitution in 1:9 dioxane-water and in methanol at 25°C are reported. These substitutions result in > 150-fold differences in their rates of acid-catalyzed solvolysis and cause marked changes in the distribution of solvent adducts and phenols resulting from isomerization. Optically pure BA-O, 7-MBA-O, 12-MBA-O, and 7,12-DMBA-O as well as their optically pure trans dihydrodiols were utilized to determine the point of attack by water in the hydrolysis reactions. In general, the reactions in aqueous dioxane (0.1 M NaClO4) obeyed the rate equation kobsd = kH[H+] + k0, where kH is the second-order rate constant for acid-catalyzed reaction and k0 is the first-order rate constant for spontaneous reaction, to provide biphasic pH-rate profiles. When ionic strength was maintained with 0.5 M KCl, however, more complex pH-rate profiles were observed for some of the arene oxides due to attack of chloride on the neutral epoxide to produce steady-state concentrations of chlorohydrins. Rate enhancement on methyl substitution is largest (kH, ca. 5-fold) when the methyl group is present in the hindered bay region (C1 or C12) or adjacent to the epoxide at C7. The combined effect of two methyl groups (7,12-DMBA-O) is additive (ca. 25-fold). Theoretical calculations (molecular mechanics by PCMODEL-PI and ab initio by GAUSSIAN 86 and 88 programs) of carbocation stability indicate the importance of steric factors in determining relative reactivity and types of products formed from substituted benz[a]anthracene 5,6-oxides.
THE DIRECTED ORTHO METALATION CONNECTION TO ARYL-ARYL CROSS COUPLING. A GENERAL REGIOSPECIFIC SYNTHESIS OF PHENANTHROLS
Fu, J.-m.,Sharp, M.J.,Snieckus, V.
, p. 5459 - 5462 (2007/10/02)
A general directed metalation-based cross coupling synthesis of phenanthrols 4 has been developed (Scheme 1); reactions of derived triflates and carbamates 10 lead to a variety of substituted phenanthrenes 7 12 (Scheme 2).
Absolute Configurations of K-Region Epoxide Enantiomers of 3-Methylcholanthrene, Benzanthracene, and Benzopyrene
Weems, Henri B.,Mushtaq, Mohammad,Yang, Shen K.
, p. 2679 - 2688 (2007/10/02)
The absolute configurations of K-region epoxide enantiomers of 3-methylcholanthrene, benzanthracene, and benzopyrene have been determined via their monomethyl ether derivatives.Methoxylation of each racemic or enantiomeric epoxide by sodium methoxide resulted in a pair of monomethyl ether derivatives, which were separated by normal-phase high-performance liquid chromatography (HPLC).The position of the methoxy group was determined by products formed by acid-catalyzed dehydration and/or demethanolization of each monomethyl ether derivative.Enantiomers of each epoxide and its methoxylated derivatives were resolved by at least two of the four Pirkle chiral stationary phase HPLC columns utilized in this study.The absolute stereochemistries of enantiomeric monomethyl ether derivatives were established by comparing their circular dichroism spectra with those of enantiomeric monomethyl ether derivatives derived from trans dihydrodiol enantiomers of known absolute configurations.The absolute configuration of each epoxide enantiomer was deduced from the location of the methoxy group and the absolute configuration of enantiomeric monomethyl ether derivatives.Results indicate that the method described is useful in general for the determination of absolute configurations of K-region epoxide enantiomers of polycyclic aromatic hydrocarbons.
