Radical substitution, heteroaromatic systems

Bowman and coworkers [69] have reported the addition of a carbon-centered radical to heteroaromatic systems substituted with a carbonyl group, followed by spontaneous oxidation to generate the cycloheptane-fused heteroaromatic compounds. Reaction of the bromides 270-272 with BuaSnH and AIBN furnished the... 

The competitive method employed for determining relative rates of substitution in homolytic phenylation cannot be applied for methylation because of the high reactivity of the primary reaction products toward free methyl radicals. Szwarc and his co-workers, however, developed a technique for measuring the relative rates of addition of methyl radicals to aromatic and heteroaromatic systems. - In the decomposition of acetyl peroxide in isooctane the most important reaction is the formation of methane by the abstraction of hydrogen atoms from the solvent by methyl radicals. When an aromatic compound is added to this system it competes with the solvent for methyl radicals, Eqs, (28) and (29). Reaction (28) results in a decrease in the amount... 

Two steps must be considered in the mechanism of homolytic acylation, in addition to the formation of the acyl radical. The first fits in with the generally accepted mechanism of homolytic aromatic substitution, that is, the addition of the acyl radical to the aromatic nucleus to give an adduct in which the unpaired electron is delocalized over the residual heteroaromatic system (u-complex 6). 

Radical substitution should therefore take place about equally easily in the heteroaromatic system and in the AH this appears to be the case.20 Nucleophilic substitution should take place more easily in heteroaromatic compounds containing atoms more electronegative than carbon (e.g., N), and most easily in positions where Nt is small and a f large the observed reactivities follow this pattern.14 Likewise electrophilic substitution should be hindered in such compounds and should take place preferentially... 

The synthetic interest in direct substitution of protonated heteroaromatic bases by carbamoyl and a-amidoalkyl radicals arises because the reaction is applicable to a variety of heteroaromatic bases having highly reactive nucleophilic positions and because a variety of amides can be used. The selectivity of attack is complete at the a- and y-positions of the heterocyclic system owing to the nucleophilic character of both carbamoyl and a-amidoalkyl radicals, The results with formamide are shown in Table VI. Quinoline with dimethylformamide gave a variety... 

Six-membered N-heteroaromatic bases are known to be deactivated systems toward electrophilic substitution. Thus, reactions following the Friedel-Crafts protocol generally give on them products substituted onto the less electron-poor positions. Otherwise, their reactions with nucleophilic carbon-centered radicals reproduce most of the Friedel-Crafts aromatic substitutions, but with opposite reactivity and selectivity. The general reaction mechanism is shown in Scheme 6. 

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