Ambident Heterocyclic Reactivity: The Alkylation of Pyrrolopyridines (Azaindoles, Diazaindenes)

Article abstract of DOI:10.1016/S0040-4020(01)87211-2

7-Methyl-6-azaindole, 7-acetamido-4-azaindole, the substituted 4-amino-, 2-methyl- and 6-methyl-7-azaindole, and the parent 4-, 5-, 6-, and 7-azaindole systems (as anions in dimethylformamide) were alkylated with a variety of primary alkylating agents.The relative importance of charge, product development, and steric approach control in determining the alkylation pattern (pyrrole versus pyridine ring alkylation) are discussed within a framework of variable S_N2 transition state structures.Frontier orbital factors appear to be relatively insignificant.The charge distribution, orbitals and energetics of these heterocyclic systems were modelled by ab initio molecular orbital calculations (STO-3G level).Specific association, involving hydrogen bonding between adjacent groups and the alkylating agent, is important in determining the alkylation pattern in some cases.