Chemoenzymatic preparation of optically active 3-(1H-imidazol-1-yl)cyclohexanol-based ionic liquids: application in organocatalysis and toxicity studies

Abstract

A straightforward and robust modular synthetic approach was developed for the asymmetric synthesis of imidazolium salts, in which several engineered molecular vectors were considered to evaluate their toxicological profile. The diastereoselective synthesis of cis-3-(1H-imidazol-1-yl)cyclohexanol was achieved by the Michael addition of imidazole to cyclohex-2-en-1-one under microwave conditions followed by reduction of the ketone. The racemic cis-alcohol obtained was successfully resolved through a lipase-catalysed kinetic resolution, Pseudomonas cepacia lipase proved to be a good biocatalyst for the exclusive acetylation of the (1R,3S)-cis enantiomer. Using the remaining (1S,3R)-cis alcohol enantiomer as a synthetic precursor, the optically active (1R,3R)-trans alcohol enantiomer was also prepared. The corresponding chiral salts and ionic liquids were obtained via quaternisation with alkyl halides, followed by anion exchange with inorganic salts. In this manner, a family of novel imidazolium-based ionic liquids was prepared, and their properties as phase-transfer catalysts in the Michael addition of diethyl malonate to trans-chalcone were analysed. The toxicity of these compounds against E. coli cells was also evaluated to understand their structural implications through the presented systematic synthetic approach.