Quinones, determination

Yu. E. Gerasimenko, A. A. Parshutkin, N. T. Poteleshenko, V. P. Poteleshenko, and V. V. Romanov, Photochromism of peri-aryloxy-p-quinones. Determination of molecular absorption coefficients for 6-phenoxy-5,ll-naphthacenequinones, Zh. Prikl. Spektr. 30, 954-956 (1979) (Russ.). 

Quinones Determine as directed under Quinones, Appendix IV. 

In Figure 6.17 the electron affinities of several substituted quinones determined from E /2 measurements, and/or charge transfer spectra, are plotted versus the current evaluated gas phase values. They are chosen to give a comparison of the values obtained by the two methods and to note the deviations from the unit slope line. The displacement of the unit slope lines by a constant amount is a systematic uncertainty. This indicates that the solution energy differences and constants used to correlate the charge transfer complex data are both a function of the electron affinity and/or the type of molecules [78]. Thus, it will be possible to reduce deviations by classifying the molecules and identifying the functional relationship. 

There is a fair amount of work reported with films at the mercury-air interface. Rice and co-workers [107] used grazing incidence x-ray diffraction to determine that a crystalline stearic acid monolayer induces order in the Hg substrate. Quinone derivatives spread at the mercury-n-hexane interface form crystalline structures governed primarily by hydrogen bonding interactions [108]. 

Br20 a dark-brown solid moderately stable at —60° (mp —17.5° with decomposition), prepared by reaction of Bt2 vapour on HgO (cf. CI2O p. 846) or better, by low-temperature vacuum decomposition of BrOa. The molecule has C2v symmetry in both the solid and vapour phase with Br-O 185 1pm and angle BrOBr 112 2° as determined by EXAFS (extended X-ray absorption fine structure). It oxidizes I2 to I2O5, benzene to 1,4-quinone, and yields OBr in alkaline solution. 

Although not a heteroaromatic compound, the case of citrinin studied by Destro and Luz ([97JPC(A)5097] and references therein) is so significant that it deserves mention here. Citrinin exists in the crystal as a mixture of the p-quinone 5a and o-quinone 5b tautomers (Scheme 3). The equilibrium ii temperature dependent and by using CPMAS NMR (Section VI,F) and, more remarkably. X-ray crystallography, the authors were able to determine the AH and AS values (the rate is extremely fast on the NMR time scale, >10 s ). 

The absolute rate constants for attack of carbon-centered radicals on p-benzoquinone (38) and other quinones have been determined to be in the range I0M08 M 1 s 1.1 -04 This rate shows a strong dependence on the electrophilicity of the attacking radical and there is some correlation between the efficiency of various quinones as inhibitors of polymerization and the redox potential of the quinone. The complexity of the mechanism means that the stoichiometry of inhibition by these compounds is often not straightforward. Measurements of moles of inhibitor consumed for each chain terminated for common inhibitors of this class give values in the range 0.05-2.0.176... 

In hydroxylation, quinones are usually obtained since the initial hydroxyl product is further oxidised. Kinetic studies on the hydroxylation of 1,3,5-tri-methoxybenzene with perbenzoic acid gave second-order rate coefficients (Table 29) which remained fairly constant for a wide variation in concentration of aromatic and acid thus indicating that the rate-determining step is bimolecular133. The variation was considered to be within the rather large experimental error for the reaction which was very fast and, therefore, studied at low temperature (—12.4 °C). Since more than one mole of acid per mole of aromatic was eventually consumed, the mechanism was formulated as... 

Reduction of monocyclic aromatic nitro compounds has been demonstrated (a) with reduced sulfur compounds mediated by a naphthoquinone or an iron porphyrin (Schwarzenbach et al. 1990), and (b) by Fe(II) and magnetite produced by the action of the anaerobic bacterium Geobacter metallireducens (Heijman et al. 1993). Quinone-mediated reduction of monocyclic aromatic nitro compounds by the supernatant monocyclic aromatic nitro compounds has been noted (Glaus et al. 1992), and these reactions may be signihcant in determining the fate of aromatic nitro compounds in reducing environments (Dunnivant et al. 1992). 

The rationale for the cyclopent[Z>]indole design discussed above was that the quinone methide would build up in solution and intercalate/alkylate DNA. Enriched 13C-NMR studies indicate that the quinone methide builds up in solution and persists for hours, even under aerobic conditions (Fig. 7.21). In contrast, the quinone methide species formed by known antitumor agents (mitomycin C) are short lived and highly reactive. The spectrum shown in Fig. 7.21 also shows the N to O acyl transfer product that we isolated and identified. However, we could not determine if the quinone methide structure actually has the acetyl group on the N or O centers. 

The results enumerated above indicate that the quinone methide species must be protonated, by either a specific or general acid, to afford a cation before it can trap a nucleophile. The pK.A determined from pH-rate profile (pKA = 6.66) is consistent with (9-protonated quinone methide pKA values of 6-7 discussed in Section 7.3.5. 

Scheme 7.25 shows the role of quinone methide energy on the cation-quinone methide equilibrium. A high pKa value for this equilibrium is expected if the energy of the quinone methide approaches that of the carbocation. To construct this cycle, we used the Ka values that we determined for the protonated ketone (pKa — —0.9) and quinone methide (pKa = 6.6). This pKa difference requires that the keto form be more stable than the quinone methide by — 10.2kcal/mol. We obtained the calculated energy difference of lO.lkcal/mol from Hartree-Fock calculations using 6-31G and STO-3G basis sets, inset of Scheme 7.25. 

Table 7.3 shows the concentrations of 1-5 that result in 50% growth inhibition (GI50) of five human cancer cell lines. Inspection of these data reveals that cytostatic activity of 1 and 3-5 depends on the thermodynamic favorability of the quinone methide species compared to the corresponding keto form. The most cytostatic prekinamycins 1 and 5 are associated with the thermodynamically stable quinone methides. In contrast, the inactive prekinamycins 3 and 4 are associated with thermodynamically stable keto tautomers. The exception is prekinamycin 2, which is cytostatic and possesses a relatively stable keto tautomer 3 compared to its quinone methide. Although the AE value for quinone methide tautomerization can predict cytostatic properties, prekinamycin 2 shows that there must be other factors determining biological activity. 

Boruah, R. C. Skibo, E. B. Determination of the pKa values for the mitomycin C redox couple by tritration, pH rate profile, and Nemst-Clark fits. Studies of methanol elimination, carbocation formation, and the carbocation/quinone methide equilibrium. J. Org. Chem. 1995, 60, 2232-2243. 

Acolbifene is also metabolized to a QM (Scheme 10.10)64 formed by oxidation at the C-17 methyl group. This QM is considerably more reactive compared to the tamoxifen quinone methide, which indicates that the acolbifene quinone methide is an electrophile of intermediate stability (Table 10.2). In addition, the acolbifene QM was determined to react with deoxynucleosides, with one of the major adducts resulting from reaction with the exocyclic amino group of adenine.64... 

Fig. 12.7a,e) it is important to realize that a protonated quinone methide QM1H + is actually a benzylic carbocation (Fig. 12.7a). Water will also add to the quinone methide under fairly neutral conditions.86-88 The isomer distribution of the resulting compounds, PI can be determined directly from or 13C (or 2D 13C/1H correlation)... 

Ralph, J. Adams, B. R. Determination of the conformation and isomeric composition of lignin model quinone methides by NMR. J. Wood Chem. Technol. 1983, 3, 183-194. 

Trans oxidative addition of CH3I to [Ir(acac)(cod)] affords the structurally determined complex [Ir(acac)(cod)(CH3)1].241 The reaction of [(Npet)2Ir]Cl, Npet = o-(diphenylphosphino)benzylide-nejethylamino, with tetrachloro-o-quinone yields the structurally characterized product (135).242 The synthesis and characterization of the water-soluble complex (136) have been described.243... 

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