HETEROCYCLIC AMBIDENT NUCLEOPHILES .5. ALKYLATION OF BENZIMIDAZOLES

Alkylation of 5-substituted benzimidazole anions with a variety of pri mary alkyl halides in both protic and aprotic solvents showed only sma ll regioselectivity, with a slight preference for reaction at N 1 for 5-nitro and N 3 for 5-methoxy systems. With 4-substituted benzimidazol e anions, alkylation gave more divergent results with the N 1 to N 3 r egioselectivity varying between 100:0 and 29:71. These alkylation patt erns are interpreted as deriving from an interplay of electrostatic, t hermodynamic, steric and associative control factors within the variab le S(N)2 transition state structures involved. In the 4-substituted se ries, proximity effects, both electrostatic field and steric non-bonde d, are clearly dominant.