Quinones, production

When a noncyclizable diphenol (e.g., 4-methylcatechol) is used, both the accumulation of the quinone product and the decrease in the oxygen concentration are linear with time, and there is no lag period. 

Scheme 13 Pathway for the oxidation of 3,5-di-tert-butylphenolate to the corresponding catechol and quinone products using dicopper species 28, via the spectroscopically observed bis(/x-oxo)phenolate intermediate 29 [190]...

Namely, these series show that monophenols react according to their oxidizability, catechols react similarly except twice as much (presumably via o-quinone production), and pyrogallol derivatives generally react as catechols if vicinal hydroxyls are free and as monophenols if not. Ellagic acid appears perhaps anomalous, but it is known that two of the four hydroxyls are considerably more acidic than the other two (II). 

Nishinaga and co-workers isolated a series of stable cobalt(III)-alkyl peroxide complexes such as (170) and (171) in high yields from the reaction of the pentacoordinated Co"-Schiff base complex with the corresponding phenol and 02 in CH2C12. Complex (170 R=Bu ) has been characterized by an X-ray structure. These alkyl peroxide complexes presumably result from the homolytic addition of the superoxo complex Co111—02 to the phenoxide radical obtained by hydrogen abstraction from the phenolic substrate by the CoUI-superoxo complex. The quinone product results from / -hydride elimination from the alkyl peroxide complex (172)561,56,565,566 The quinol (169) produced by equation (245) has been shown to result from the reduction of the CoIU-alkyl peroxide complex (170) by the solvent alcohol which is transformed into the corresponding carbonyl compound (equation 248).561... 

However, because catechol and hydroquinone are oxidized at less positive potentials ( + 1.32 V and +1.18 V, respectively), the only detectable products are the o- and p-quinones via an overall four-electron (ECECECEC) oxidation. The data for substituted phenols (Table 12.4) indicate that election-donating substituents cause phenol to become more nucleophilic (a stronger Lewis base) and easier to oxidize. Anisole (PhOMe) is more resistant to election removal ( + 1.75 V vs. SCE) than phenol ( + 1.55 V vs. SCE), but undergoes electron removal via a similar path [Eq. (12.38)] to yield the same quinone products. 

The synthesis of the aglycone of the antibiotic giivocarcin-M was accompiished by T.C. McKenzie et ai. by a sequentiai Meerwein arylation-Diels-Alder cycloaddition.The anthraniiic methyi ester substrate was first subjected to diazotization and then the resuiting diazonium chioride was coupied to 2,6-dichiorobenzoquinone in water to afford the quinone product in moderate yieid. it is important to mention that the Meerwein arylation was conducted in water at 80 C in the absence of a cataiyst. 

A series of p-aryloxy- and p-alkoxyphenylnitrenium ions have been generated in aqueous solutions by photolysis of the parent azides, whereupon the resulting nitrenes are protonated. Hydration of these cations at the para position leads via hemiacetal or halohydrin intermediates to quinone imines, which finally hydrolyse to the ultimate quinone products. In flash-photolysis studies of these reactions it was shown that nitrenium ion hydration occurs on the ps timescale, hemiacetal or halohydrin breakdown on the MS timescale, and the final imine hydrolysis over minutes. 

Approximately 50% of the benzo[a]pyrene that was intratracheally instilled in hamsters was metabolized in the nose (Dahl et al. 1985). The metabolite produced in the hamster nose included tetrols, the 4,5-, 7,8-, and 9,10-dihydrodiol. quinones, and 3-and 9-hydroxybenzo[a]pyrene. Similar metabolites were detected in nasal and lung tissues of rats inhaling benzo[a]pyrene (Wolff et al. 1989b). The prevalence of quinone production was not seen in hamsters as it was in rats (Dahl et al. 1985 Weyand and Bevan 1987a, 1988). In monkeys and dogs, dihydrodiols, phenols, quinones, and tetrols were identified in the nasal mucus following nasal instillation of benzo[a]pyrene (Petridou-Fischer et al. 1988). in vitro metabolism of benzo[a]pyrene in the ethmoid turbinates of dogs resulted in a prevalence of phenols (Bond et al. 1988). However, small quantities of quinones and dihydrodiols were also identified. 

Rat liver microsomes also catalyzed benzo[a]pyrene metabolism in cumene hydroperoxide (CHP)-dependent reactions which ultimately produced 3-hydroxybenzo[a]pyrene and benzo[a]pyrene-quinones (Cavalieri et al. 1987). At low CHP concentrations, 3-hydroxybenzo[a]pyrene was the major metabolite. As CHP concentrations increased, levels of quinones increased and levels of 3- hydroxybenzo[a]pyrene decreased. This effect of varying CHP levels was reversed by preincubating with pyrene. Pyrene inhibited quinone production and increased 3-hydroxybenzo[a]pyrene production. Pretreatment with other PAHs like naphthalene, phenanthrene, and benz[a]anthracene nonspecifically inhibited the overall metabolism. The binding of benzo[a]pyrene to microsomal proteins correlated with quinone formation. This suggested that a reactive intermediate was a common precursor. The effects of pyrene on benzo[a]pyrene metabolism indicated that two distinct microsomal binding sites were responsible for the formation of 3-hydroxybenzo[a]pyrene and benzo[a]pyrene-quinone (Cavalieri et al. 1987). 

The post-y oxidation is markedly retarded by the three additives (Figures 5 and 6). The phenolic additive is outstanding but its performance is marred by the yellowing of the film as the phenol is converted to quinone products. Horng and Klemchuk have found that phenolic, phosphite and a secondary hindered amine were essentially unchanged by a 2.5 Mrad. y-dose, and so available to suppress the post-ydeterioration (6). 

Various kinetic experiments and product analyses indicate that the catechol oxidation catalyzed by the bispidine-copper(ll) complexes proceeds via the mechanism shown in Scheme 19. There is one quinone product per cycle and dioxygen is reduced to hydrogen peroxide. Interestingly, all individual steps (1 2 3 1) are relatively fast... 

In anticipation of possible complications, a model trimethoxybenzene amide 54 was made and explored with various oxidants (Scheme 17). CAN and silver oxide rapidly produced a quinone, not azaquinone, in near quantitative yield. Other oxidants as listed were not as successful. Initially, through NMR comparison to related compounds it was assumed that the quinone product obtained was the para-quinone. Only after considerable effort was a crystal suitable for X-ray analysis obtained. Surprisingly, this unambiguous result confirmed that the quinone product... 

Figure 6.19. Oxidation of a polyhalogenated ring via an ipso mechanism that does not involve formation of an epoxide metabolite but rather an addition-elimination reaction that directly yields a quinone product.

A classical oxidation reaction that involves radicals is the phenolic oxidative coupling, which is introduced in Section 10.5.A.i. In this reaction, electron transfer from a metal salt to a bis(phenol) leads to intramolecular coupling and a quinone product. The early yields were poor. For example, Barton reacted 219 with potassium ferricyanide [K3(Fe(CN)6l and the product was aryl radical 220. This radical reacted with the second phenolic ring in an intramolecular process that gave 221. Loss of a hydrogen led to the quinone narwedine (222) in a synthesis of galanthamine. 53 jjje yield of 222, however, was only 1.4% under optimal... 

The following experiments illustrate that when studying the involvement of phospholipase in the host-pathogen interaction, the total contribution of enzyme of host origin may be considerably higher than previously realized. Rodionov and Zakharova (32) recently reported very high rates of autolytic hydrolysis of membrane lipids in homogenates of potato leaves (26-37% of the phospholipids were hydrolyzed after 2 h at 0-1 ). Our laboratory recently confirmed this observation and proceeded to study sosie of the properties of the lipolytic acyl hydrolase activity in potato leaves (6). Lipolytic acyl hydrolase activity is apparently inactivated by polyphenol oxidase or its toxic quinone products. 

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