AMBIDENT HETEROCYCLIC REACTIVITY - THE ALKYLATION OF PYRROLOPYRIDINES (AZAINDOLES, DIAZAINDENES)

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(N)2 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.