Radical cations nucleophiles

Oxidative Alkoxylation of Nitrones to a-Alkoxy Nitrones and a-Alkoxy Substituted Nitroxyl Radicals The first direct experimental evidence of the possibility to carry out radical cation nucleophilic addition to nitrones with the formation of nitroxyl radicals has been cited in Section 2.4. Further, such a reaction route was referred to as inverted spin trapping this route is an alternative to a conventional spin trapping (508-512). Realization of either mechanism depends on the reaction conditions namely, on the strength of both nucleophile and oxidant. The use of strong oxidants in weak nucleophilic media tends to favour the radical cation mechanism... 

Starting radical cation Nucleophile Solvent k (M s-1) Refs. 

Electrochemically generated solutions of radical-cations will react with nucleophiles in an inert solvent to generate a radical intemiediate. Under these conditions the intermediate is oxidised to the carboniiim ion by a further radical-cation. Generally, an aromatic system is then reformed by loss of a proton. Reactions of 9,10-diphenylanthracene radical-cation nucleophiles in acetonitrile are conveniently followed either by stop flow techniques or by spectroelectrochemistry. Reaction with chloride ion follows the course shown in Scheme 6.2, where the termination... 

Comparison of the reactivities of both 9-methylanthracene and 9,10-dimethylanthracene radical cations with those of pyridine and 2,6-lutidine shows that in the absence of severe steric effects radical cation-nucleophile combination is kinetically favored over direct proton transfer, even though the latter process is highly exergonic. Because the addition step cannot usually be readily detected, however, experimental evidence does not usually enable distinction between addition-elimination and direct proton transfer mechanisms. 

Methionine. The reaction of superoxide radical anions (02 with sulfide radical cation-nucleophile complexes might represent an efficient sulfoxide-forming process in peptides and proteins containing methionine under conditions where significant amounts of sulfide radical cation complexes and superoxide are formed simultaneously. The rate constant for the reaction of 02 with the (S.-. N)+ complex was found to be ca. 3-fold slower as compared to that ofthe reaction with the (S.-.Sf complex. This drop in reactivity may, in part, reflect the lower probability of 62 to encounter S-atom in the (S.-.N) complex as... 

An interesting method for the substitution of a hydrogen atom in rr-electron deficient heterocycles was reported some years ago, in the possibility of homolytic aromatic displacement (74AHC(16)123). The nucleophilic character of radicals and the important role of polar factors in this type of substitution are the essentials for a successful reaction with six-membered nitrogen heterocycles in general. No paper has yet been published describing homolytic substitution reactions of pteridines with nucleophilic radicals such as alkyl, carbamoyl, a-oxyalkyl and a-A-alkyl radicals or with amino radical cations. 

Xenon difluoride [4, 5, 7, 8,10] is a white crystalline material obtained through the combination of fluorine and xenon m the presence of light The reagent is commercially available and possesses a relatively long shelf-life when stored cold (freezer) Xenon difluoride is very effective for small-scale fluormation of alkenes and activated nucleophilic substrates. The reactions are usually conducted between 0 °C and room temperature in chloroform or methylene chloride solutions Hydrogen fluoride catalysis is sometimes helpful Xenon difluoride reacts in a manner that usually involves some complexation between the substrate and reagent followed by the formation of radical and radical cation intermediates... 

In conclusion, it is very likely that the influence of solvents on the change from the heterolytic mechanism of dissociation of the C —N bond in aromatic diazonium ions to homolytic dissociation can be accounted for by a mechanism in which a solvent molecule acts as a nucleophile or an electron donor to the P-nitrogen atom. This process is followed by a one- or a two-step homolytic dissociation to an aryl radical, a solvent radical, and a nitrogen molecule. In this way the unfavorable formation of a dinitrogen radical cation 8.3 as mentioned in Section 8.2, is eliminated. 

Elegant evidence that free electrons can be transferred from an organic donor to a diazonium ion was found by Becker et al. (1975, 1977a see also Becker, 1978). These authors observed that diazonium salts quench the fluorescence of pyrene (and other arenes) at a rate k = 2.5 x 1010 m-1 s-1. The pyrene radical cation and the aryldiazenyl radical would appear to be the likely products of electron transfer. However, pyrene is a weak nucleophile the concentration of its covalent product with the diazonium ion is estimated to lie below 0.019o at equilibrium. If electron transfer were to proceed via this proposed intermediate present in such a low concentration, then the measured rate constant could not be so large. Nevertheless, dynamic fluorescence quenching in the excited state of the electron donor-acceptor complex preferred at equilibrium would fit the facts. Evidence supporting a diffusion-controlled electron transfer (k = 1.8 x 1010 to 2.5 X 1010 s-1) was provided by pulse radiolysis. 

Thus, polymerization will always occur when kp > k<, -E k ([solv] + pC ]). In the case of highly electron-donating substituents the stability of the radical cations may be so great that k > kp + k ([solv] -E PC ]) and most of the ions diffuse into the solution. By contrast, if — given electron-withdrawing subsituents and high oxidation potential — k ([solv] + PC ]) becomes greater than kp -E k, then the nucleophilic addition will dominate and the polymerization will be suppressed. 

The efficiency of this injection system depends upon the reaction conditions. 02) which traps the first formed radical 6, reduces the yield of enol ether 8. Therefore, we are using our assay under anaerobic conditions. Also, the pH of the solution influences the product ratio because it changes the nucleophilicity of the water. Figure 1 shows how the efficiency of the electron transfer is reduced as the pH value increases from 5.0 to 7.0 [5]. This is in accord with an increase of the nucleophilicity of water, which traps the radical cation (7—>9+10) in competition to the electron transfer step (7—>8). 

At present a variety of studies with PAH, as well as other chemicals, suggest that metabolic activation in target tissues can occur by one-electron oxidation (6,7). The electrophilic intermediate radical cations generated by thTs mechanism can react directly with various cellular nucleophiles. In this paper, we will discuss chemical, biochemical and biological evidence which indicates that one-electron oxidation plays an important role in the metabolic activation of PAH. 

Nucleophilic Trapping of Radical Cations. To investigate some of the properties of Mh radical cations these intermediates have been generated in two one-electron oxidant systems. The first contains iodine as oxidant and pyridine as nucleophile and solvent (8-10), while the second contains Mn(0Ac) in acetic acid (10,11). Studies with a number of PAH indicate that the formation of pyridinium-PAH or acetoxy-PAH by one-electron oxidation with Mn(0Ac)3 or iodine, respectively, is related to the ionization potential (IP) of the PAH. For PAH with relatively high IP, such as phenanthrene, chrysene, 5-methyl chrysene and dibenz[a,h]anthracene, no reaction occurs with these two oxidant systems. Another important factor influencing the specific reactivity of PAH radical cations with nucleophiles is localization of the positive charge at one or a few carbon atoms in the radical cation. 

Scheme 1. Mechanism of trapping of BP radical cation by a nucleophile (Nu).

The overall conclusion from the reaction of BP and 6-substituted BP radical cations with nucleophiles of various strengths is that weak nucleophiles display higher selectivity toward the position of highest charge localization. Thus another important factor in the chemical reactivity of radical cations is represented by the strength of the nucleophile. 

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