Synthesis and structural characterization by NMR and X-ray of new Morita-Baylis-Hillman adducts derived from 7-chloroquinoline

Abstract

Herein we describe the design, synthesis and structural characterization by NMR and X-ray of new molecular hybrids 4a-4c containing the nitroaromatic MBHA moiety and the 7-chloroquinoline pharmacophores, linked by an aliphatic spacer as a model for antiprotozoal drugs. Firstly, the 4,7- dichloroquinoline (7) reacted with excess of ethylene glycol, through a SNAr promoted by t-BuOK, to prepare the 2-(7-chloroquinolin-4-yloxy)ethanol (6) in 98% isolated yield. Then, the novel 2-(7- chloroquinolin-4-yloxy) ethyl acrylate (5) was synthesized in 78% isolated yield by reacting the alcohol (6) with acryloyl chloride and TEA in CH2Cl2. Finally, this acrylate (5) reacted with o-nitrobenzaldehyde, m-nitrobenzaldehyde and p-nitrobenzaldehyde through Morita-Baylis-Hillman reactions promoted by DABCO at room temperature, using t-BuOH:Water (9:1) as solvent, to afford the new hybrids 4a-4c in 73e76% isolated yields. Three-dimensional structures were characterized in both monomeric and intermolecular packing by X-Ray experiments.