Radical intramolecular hydrogen bonding, effect

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. 

The antioxidant activity of phenol is also increased by the presence of additional hydroxyl group in the ortho or para positions. An example of such an antioxidant is TBHQ. The effectiveness of 1,2-dihydroxybenzene derivatives is attributed to a phenoxyl radical stabilised by an intramolecular hydrogen bond (11-8). The activity of 2-methoxyphenol is lower, because the generated radical cannot be stabihsed by a hydrogen bond. The antioxidant activity of 1,2-and 1,4-dihydroxybenzene is partly caused by the fact that the semi-quinone radical can be further oxidised to the corresponding o-quinone orp-quinone, respectively, by reaction with another lipid radical (Figure 11.7) or may disproportionate to the corresponding quinone and hydroquinone. 

The peroxyl radical of a hydrocarbon can attack the C—H bond of another hydrocarbon. In addition to this bimolecular abstraction, the reaction of intramolecular hydrogen atom abstraction is known when peroxyl radical attacks its own C—H bond to form as final product dihydroperoxide. This effect of intramolecular chain propagation was first observed by Rust in the 2,4-dimethylpentane oxidation experiments [130] ... 

Trifluoroethanol (TFE, CE3CH2OH) also demonstrates high H-bond activity. The dyad system in which a radical and electron-donor parts are linked directly undergoes intramolecular electron transfer on substitution of TEE for toluene as a solvent. The transition was interpreted as a marked effect of hydrogen bonding (or reversible protonation) of the anionic R-0 structure with TFE (Nishida et al. 2005). Scheme 5.17 depicts this transition. 

Recent interest in the use of N-unsubstituted 2-quinolones stems from the fact, that they coordinate effectively to chiral lactam-based templates via two hydrogen bonds. The prototypical template to be used in photochemical reactions is compound 115, which can be readily prepared from Kemp s triacid [108]. The template is transparent at a wavelength X > 290 nm, and can be nicely used in stoichiometric amounts for enantioselective photochemical and radical reactions [109]. Conditions which favor hydrogen bonding (nonpolar solvent, low temperature) are required to achieve an efficient association of a given substrate. The intramolecular [2 + 2]-photocycloaddition of 4-alkylquinolone 114 proceeded in the presence of 115 with excellent enantioselectivity, and delivered product 116 as the exclusive stereoisomer (Scheme 6.41) [110]. Application of the enantiomer ent-115 ofcomplexing agent 115 to the reaction 111 —> 112 depicted in Scheme 6.40 enabled enantioselective access to (+ )-meloscine [111]. 

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