Synthesis of quinoxaline derivatives aromatic nucleophilic substitution of hydrogen

The electrophilic nature of quinoxaline has been explored in the vicarious nucleophilic substitution (VNS) of hydrogen with various carbanions as nucleophiles in an attempt to develop a general method for functionalizing the heterocyclic ring. Only poorly stabilized nitrile carbanions were found to give the VNS products. 2-Chloroquinoxaline gave products of S N Ar of chlorine preferentially. A variety of quinoxaline derivatives containing cyanoalkyl, sulfonylalkyl, benzyl or ester substituents, including fluorinated ones, have been prepared in the VNS reactions with quinoxaline N -oxide. Vicarious nucleophilic substitution allows for direct functionalization of the quinoxaline ring, particularly in quinoxaline N -oxide, with substituents containing nitrile, ester, amide or sulfone groups, as well as fluorine atoms.