Free radicals nucleophilic character

Methyl free radicals, generated either by thermolysis of lead tetracetate in acetic acid solution (401) or by radical cleavage of dimethylsulfoxide by H2O2 and iron (II) salts (408), afford 2- and 5-methylthiazole in the proportion of 86 and 14%, respectively, in agreement with the nucleophilic character of alkyl free radicals and the positive charge of the 2-carbon atom of the thiazole (6). 

CycJohexyl free radicals, generated by photolysis of t-butyl peroxide in excess cyclohexane, also possess nucleophilic character (410). Their attack on thiazole in neutral medium leads to an increase of the 2-isomer and a decrease of 5-isomer relative to the phenylation reaction, in agreement with the positive charge of the 2-position and the negative charge of the 5-position (6). 

The carbon atoms of azole rings can be attacked by nucleophilic (Section 4.02.1.6 electrophilic (Section 4.02.1.4) and free radical reagents (Section 4.02.1.8.2). Some system for example the thiazole, imidazole and pyrazole nuclei, show a high degree of aromati character and usually revert to type if the aromatic sextet is involved in a reaction. Othei such as the isoxazole and oxazole nuclei are less aromatic, and hence more prone to additio reactions. 

It has been mentioned that some free radicals (e.g., chloro) are electrophilic and some (e.g., tert-hvAy ) are nucleophilic. It must be borne in mind that these tendencies are relatively slight compared with the electrophilicity of a positive ion or the nucleophilicity of a negative ion. The predominant character of a free radical is neutral, whether it has slight electrophilic or nucleophilic tendencies. 

Moreover it has been shown that PV0CC1 prepared by free-radical polymerization of vinyl chloroformate (V0CC1) is an atactic polymer having a Bernouillian statistical distribution as expected (J[9). In order to extend our studies on the chemical modification of PV0CC1, the stereoselective character of the nucleophilic substitution of the chloroformate units with phenol has been examined by the study of the 13c-NMR spectra of partly modified polymers in the region of the aliphatic methine carbon atoms. The results obtained in this field are presented here. 

Free radical substitution of pyridines usually occurs principally at position 2 (Table 25), which is in agreement with theoretical calculations (69CCC1110). 2-Substitution is more favored in methylation than in phenylation of pyridine. This suggests that the methyl has more nucleophilic character than the phenyl radical. Furthermore, methylation of pyridine in acidic solution gives 13-fold excess of 2- over 4-substitution, although the overall yield is low. Alkyl and aryl radicals have been generated from diverse sources (Table 25). 

Consideration of reasonable mechanisms for producing formic acid from an aldose led to the hypothesis that the sugar forms an addition product with the hydroperoxide anion, comparable with an aldehyde sulfite or the addition product of aldoses with chlorous acid (52). The intermediate product (12) could decompose by a free-radical or an ionic mechanism. In the absence of a free-radical catalyst, the ionic mechanism of Scheme VIII seems probable. By either mechanism the products are formic acid and the next lower sugar. The lower sugar then repeats the process, with the result that the aldose is degraded stepwise to formic acid. Addition of the hydroperoxide anion to the carbonyl carbon is in accord with its strong nucleophilic character (53) and with certain reaction mechanisms suggested in the literature (54) for related substances. 

This reaction is based on the proposition that the sensitivity to polar effects in free-radical chemistry is the result of polarity and polarizability of both the radical and the substrate. This means that the polarity of the heteroaromatic base plays a key role in the process. Actually, the nucleophilic character of an alkyl radical, for example, is not so marked as to justify the addition to the N-heteroaromatic base, and in fact either no substitution occurs or low yields and selectivity are observed. 

Generally, as the potential energy level of SOMO increases (becomes a more reactive radical), free radicals have nucleophilic character, while as the potential energy level of SOMO decreases (becomes a stable radical), free radicals have electrophilic character. Thus, when effective radical reactions are required, small energy difference in SOMO-HOMO or SOMO-LUMO interactions is necessary. For example, the relative reactivities of radical addition reactions of a nucleophilic cyclohexyl radical to alkenes,... 

This review focuses on free radical-mediated stereoselective bond construction in which the carbonyl group plays a key role. Reaction at the carbonyl group as well as on carbons alpha and beta are described. The general reaction characteristics of these reactive intermediates are as follows. The acyl radicals are nucleophilic in character and thus they react easily with electrophilic acceptors. On the other hand, radicals on carbon alpha to the carbonyl are electrophilic in nature and their reactivity matches with nucleophilic partners. The majority of reactions at carbon beta to the carbonyl are in a, -unsaturated systems and in these the beta carbon is electrophilic. 

A free radical, or univalent atom, is a chemical system like any other x and ri can be found for it, and Table 3.11 shows a listing of such data for a number of important radicals. The acid-base character of free radicals has been recognized for some time. It is common to speak of electrophilic radicals, such as Cl, and nucleophilic radicals, such as (CH3)C. Table 3.11 is a quantitative ordering of these descriptions. The alkali metal atoms could also be added to the list. These would be the most nucleophilic, or best electron donors. 

To account for these unusual results and the role of the free-radical character, a mechanism that implies that NH—CO—PTM- is a good leaving group in 8, 2 reactions has been proposed. It is based on the quantum-mechanical approach used to account for the kinetics of nucleophilic substitution in benzyl halides, which involves a diradicaloid configuration in the relevant transition state. The latter would be particularly stabilized by the radical character of the labelled glycine. 

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