Conformation and ortho steric effects in a series of 2‐(pyrazol‐1‐yl)quinolines

Abstract

AbstractNine 2‐(pyrazol‐1‐yl)‐4‐methylquinolines bearing substituents on the pyrazole 3‐ or 5‐positions (H, Me, Et, i‐Pr, t‐Bu) were regioselectively synthesized either using the direct condensation of 2‐chloro‐4‐methylquinoline and sodium salt of 3(5)‐substituted pyrazoles or by treatment of 2‐hydrazino‐4‐methylquinoline with an appropriate β‐ketoaldehyde. The 1H and 13C chemical shifts were discussed taking into account the preferred conformation about the C‐2‐N‐1′ bond as calculated by the AM1 Hamiltonian. It appears that 5‐ethyl and 5‐isopropyl substituted derivatives present short C‐H‐N‐1 interactions. Ortho steric effects appear to be responsible for these conformations.