Simple Quinones

The close electrochemical relationship of the simple quinones, (2) and (3), with hydroquinone (1,4-benzenediol) (4) and catechol (1,2-benzenediol) (5), respectively, has proven useful in ways extending beyond their offering an attractive synthetic route. Photographic developers and dye syntheses often involve (4) or its derivatives (10). Biochemists have found much interest in the interaction of mercaptans and amino acids with various compounds related to (3). The reversible redox couple formed in many such examples and the frequendy observed quinonoid chemistry make it difficult to avoid a discussion of the aromatic reduction products of quinones (see Hydroquinone, resorcinol, and catechol). 

Because of the high vapor pressure of the simple quinones and their penetrating odor, adequate ventilation must be provided in areas where these quinones are handled or stored. Quinone vapor can harm the eyes, and a limit of 0.1 ppm of 1,4-benzoquinone in air has been recommended. Quinone in either sohd or solution form can cause severe local damage to the skin and mucous membranes. Swallowing benzoquinones may be fatal the LD q in rat is 130 mg/kg orally and 0.25 mg/kg intravenously. There is insufficient data concerning quinones and cancer. The higher quinones are less of a problem because of their decreased volatihty (118—120). 

REVERSIBLE ALKYLATION OF DEOXYNUCLEOSIDES BY A SIMPLE QUINONE METHIDE... 

Richard, J. P. Mechanisms for the uncatalyzed and hydrogen ion catalyzed reactions of a simple quinone methide with solvent and halide ions. J. Am. Chem. Soc. 1991, 113, 4588 1595. 

Filar, L. J. Winstein, S. Preparation and behavior of simple quinone methides. Tetrahedron Lett. 1960, 25, 9-16. 

Simple Quinones. - Greci and colleagues have detected semiquinones arising from the photochemical (300-400 nm) reduction of 1,4-benzoquinone, Q0 and Qiq (section 6.1). In many cases, radicals derived from the electron donor were also detected. Analysis using Marcus theory led to the proposal of a mechanism involving H-atom transfer to the triplet quinone.150... 

The mechanism for the uncatalysed and H+-catalysed reactions of simple quinone methides with solvent and halide ions has been investigated. The observed differences in the isotope effects for addition of HX (X = Hal) and ROH are consistent with a stepwise mechanism for the H+-catalysed addition of solvent and concerted mechanism for the H+-catalysed reactions of halide ions79. 

The following tests will be found useful for the detection of simple quinones. 

Reaction with semicarbazide hydrochloride. Many simple quinones yield crystalline mono-semicarbazones by the following procedure. Dissolve 0.2 g of semicarbazide hydrochloride in a little water, add 0.2 g of the quinone and warm. The mono-semicarbazone is immediately formed as a yellow precipitate. Filter and recrystallise from hot water any bis-semicarbazone will remain undissolved. 

Kresge and coworkers, and McClelland et al.39 have generated o-quinone methide,50,5 -quinone methide,52 and related simple quinone methides as products of photolytic cleavage of 2-hydroxybenzyl and 4-hydroxylbenzyl derivatives.53 58 The results of studies on the mechanism for nucleophile addition to these simple quinone methides are summarized in latter sections of this chapter. 

Dimethyl quinone methide (38a, Ri = CH3,R2 = H) was one of the first spectroscopically characterized simple quinone methides. This quinone methide was generated in alkaline aqueous solution from chloride and acetate precursors H-38a-Cl and H-38a-OAc.68 Stable quinone methides such as 38b-e (Scheme 19) were generated from chloride precursors H-38-C1.169,70... 

Fig. 4 (A) Free energy reaction profile for the reversible addition of Br to the di-Q -CF3-substituted quinone methide 48, constructed using rate and equilibrium data from Ref.91 (B) Free energy reaction profile for the reversible addition of Br to the simple quinone methide p-1, constructed using rate and equilibrium data from Ref.52 These nucleophile addition reactions show similar thermodynamic driving force, but both the formation and reaction of 48 are slow because of the large intrinsic barrier A for nucleophile addition.

During my early years as an assistant professor at the University of Kentucky, I demonstrated the synthesis of a simple quinone methide as the product of the nucleophilic aromatic substitution reaction of water at a highly destabilized 4-methoxybenzyl carbocation. I was struck by the notion that the distinctive chemical reactivity of quinone methides is related to the striking combination of neutral nonaromatic and zwitterionic aromatic valence bond resonance structures that contribute to their hybrid resonance structures. This served as the starting point for the interpretation of the results of our studies on nucleophile addition to quinone methides. At the same time, many other talented chemists have worked to develop methods for the generation of quinone methides and applications for these compounds in organic syntheses and chemical biology. The chapter coauthored with Maria Toteva presents an overview of this work. 

Quinone derivatives such as quinone methides (the monomethylene analogues of quinones) have also been extensively studied ([183] and references cited therein) because they possess biological activity, particularly as antitumor agents. The first thermally stable quinone methide having no substituents in the methylene group ( simple quinone methide ) was crystallographically characterized [183a], It was shown that stabilization of the quinone methide can be achieved by complexation to a transition metal center (5.25) ... 

The photochemistry of the methoxyhydroquinone A / methoxyquinone D couple in solution was extensively studied in our laboratories [14]. It involves, as for the reactivity of other simple quinones [12, 15], the formation of a neutral semiquinone radical which is able, in the low viscosity medium, such as fluid... 

The wide occurrence of quinones [79] makes this a particularly important class of compounds and this fact is reflected by several NMR investigations of quinones and related compounds [52,53,55,60,67,80,81]. Data for representative simple quinones and one quinone methide are shown below. 

Sodium dithionite, Na2S204, decreased the remission function at all wavelengths greater than 300 nm, but the largest decreases occurred in the visible region. Polcin and Rapson [93] attributed this to the reduction of simple quinones and coniferaldehyde. Kuys and Abbot [99] made similar observations in a spectroscopic study of dithionite bleaching of radiata pine TMR However, they suggested that coniferaldehyde was reduced by sodium bisulfite formed as a dithionite oxidation product, not by dithionite itself. 

This suggestion, coupled with the mouse skin-painting bioassay results reported by Takizawa (3865a) that several simple quinones such as 2,5-cyclohexadiene-l,4-dione (p-benzoquinone), 1,2-naphthalenedione (1,2-naphthoquinone), and 1,4-naphthalenedione (1,4-naphthoquinone) were tumorigenic to mouse skin, raised serious questions about the desirability of adding phenols to the tobacco blend to enhance the odor and flavor of its smoke. Despite the many studies in which benzene was used as the solvent for testing of the tumorigenicity of PAHs, benzene seldom induced tumors in... 

Takizawa (3865a) reported that several simple quinones [2,5-cyclohexadiene-l,4-dione (/i-benzoquinone), 1,2-... 

The most basic structural model for anthracyclines adriamycin (doxorubicin) and daunomycin (daunorubicin) was considered to be tiie strongly intramolecularly hydrogen-bonded naphthazarin (5,8-dihydroxy-1,4-naphthoquinone) (Section 3.2). It is usually customary to study the way in which such simple quinones form radicals in order to gain insight into the way more complex quinones might produce toxic and other effects. This is more so as the radical centres in the complex molecules are usually located in these simpler model structures. Treatment of naphthazarin will also demonstrate how various data may be compiled and compared. 

It is amazing that quinones have sustained interest of radiation chemists for over three decades. The basic radiation chemistry of simple quinones and their simple derivatives is now well-understood. Therefore, efforts have to be diverted to complex derivatives of quinones, as the characteristics of the parent as well as the semiquinones will depend heavily on the perturbing groups/rings present. The accumulated data will give a clear insight into the perturbation effect of the overall substitution. 

A single diquinone, BE-45985X (28), has been isolated previously from nature [42]. Diquinones usually have a higher oxidation potential than simple quinones, so that rapid reduction by substrate components occurs. The stability, especially in the case of 27b, is certainly due to the sulfur substituent, which lowers the oxidation potential. The new celastramycins exhibited moderate antibacterial activity against Escherichia coli. Staphylococcus aureus, and Bacillus subtilis. 

This behavior is typical of simple quinones in aprotic solution. " However, the electrochemical behavior of 2,3,5-TMHQ and a-tocopherylquinone in acetonitrile is altered considerably by the addition of a weak acid such as ethyl malonate (Figure 19). Thus, the peak Ic process remains unchanged but reduction peak lie broadens and shifts towards more positive potentials. In addition peak Ila, corresponding to electrooxidation of the quinone dianion... 

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