Heterocyclic Ambident Nucleophiles. V. Alkylation of Benzimidazoles

Abstract

Alkylation of 5-substituted benzimidazole anions with a variety of primary alkyl halides in both protic and aprotic solvents showed only small regioselectivity , with a slight preference for reaction at N1 for 5-nitro and N3 for 5-methoxy systems. With 4-substituted benzimidazole anions, alkylation gave more divergent results with the N1 to N3 regioselectivity varying between 100:0 and 29:71. These alkylation patterns are interpreted as deriving from an interplay of electrostatic, thermodynamic, steric and associative control factors within the variable S_N2 transition state structures involved. In the 4-substituted series, proximity effects, both electrostatic field and steric non-bonded, are clearly dominant.