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

Abstract

Nine 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.