Homolytic alkylation of heteroaromatic bases : The problem of monoalkylation

Article abstract of DOI:10.1016/S0040-4020(01)82033-0

The silver-catalyzed decarboxylation of carboxylic acids by persulphate leads to alkyl radicals, which have been utilized for the selective alkylation of heteroaromatic bases. The method is particularly efficient in a water-chlorobenzene two-phase system for two reasons : it considerably increases the selectivity in monoalkylation when more positions of high nucleophilic reactivity (i.e. α and γ) are available in the heterocyclic ring (i.e. quinoline , 4-cyano- and 4-ethylpyridine, pyrazine , quinoxaline etc.) and it determines a much higher efficiency for the radical sources when the silver salt catalysis is deactivated by complexation of the salt with the heterocyclic compound . The high selectivity in monoalkylation has been obtained by the combination of polar effects and the increased lipophilicity of the alkylated product, which makes its extraction from the aqueous solution by the organic solvent easier.