73902-61-1Relevant articles and documents
Ambident heterocyclic reactivity: Alkylation of 2-substituted-4-methylbenzimidazoles
Haque, M. Rezaul,Rasmussen, Malcolm
, p. 5535 - 5554 (1994)
The regioselectivities were determined for alkylations of 4-methyl-, 2,4-dimethyl-, 2-amino-4-methyl-, 2-chloro-4-methyl-, 2-ethoxy-4-methyl-benzimidazole, and 4-methylbenzimidazolone (as anions in dimethylformamide) with a variety of primary alkylating agents. These N1/N3 regioselectivities are correlated with the second order rate constants for benzylation (benzyl chloride/dimethylformamide/30°) of these heterocyclic anions under comparable conditions. Altering the alkylating agent, R'CH2Cl, causes movement along the loose-tight axis of S(N)2 transition state structures and produces substantial changes in regioselectivity. Variations along the early-late S(N)2 axis, caused by altering the 2-substituent in the 2-R-4-methylbenzimidazole anions, are much less effective in inducing changes in alkylation regioselectivity. The combined results are consistent with dominant 'steric approach control' for the alkylations, where the magnitude of the steric effect is critically dependent on the length of the developing N---C bond in the variable geometry S(N)2 alkylation transition states involved. Unequal steric effect of 2-substituents on N1 and N3 alkylations and their variation with alkylating agent are explained by invoking the geometry of roughly conical 'approach corridors' to the nitrogen alkylation sites. Temperature effects on these regioselectivities are small for most systems.
Ambident Heterocyclic Reactivity: Alkylation of 4-Substituted and 2,4-Disubstituted Benzimidazoles
Haque, M. Rezaul,Rasmussen, Malcolm
, p. 1523 - 1536 (2007/10/02)
The N1/N3-alkylation patterns of 4-amino-, 4-methyl- and 4-nitro-benzimidazole anions, and their 2-methyl analogues, with a standard set of primary alkyl halides (in dimethylformamide, 30 deg) have been determined and compared.The observed regioselectivities are dominated by proximal effects - electrostatic field, non-bonded steric and in some cases specific association (hydrogen bonding) - the interplay of which is critically dependent on the (variable) geometries of the SN2 transition states involved, in particular on the N---C distance of the developing N-alkyl bonds.The presence of a symmetrically placed 2-methyl group produces an enhanced N1/N3 site selectivity, very sensitive to the loose-tight nature of the transition state.Halide leaving group effects on butylation regioselectivities of 2-unsubstituted, 2-ethoxy-, 2-methyl- and 2-chloro-4-methylbenzimidazole anions, whilst small, are consistent with a Bell-Evans-Polanyi analysis of SN2 transition state variations, with the earlier transition states of CH3(CH2)3I leading to reduced regioselectivities.
