Synthesis and Characterization of Potentially Biologically Active Derivatives of Polyhydroquinoline and Quinoline Ring Systems

Abstract

Multi-component reactions (MCRs) have emerged as an efficient and powerful tool in modern synthetic organic chemistry allowing the facile creation of several new bonds in a one-pot reaction. Clearly, for multi-step synthetic procedures, the number of reactions and purification steps is among the most important criteria for the efficiency and practicability of a process The classical four-component Hantzsch condensation provides access to pharmaceutically active polyhydroquinolines. We had carried out the reactions of cyclohexanone or cyclohexane dione or dimedone with malononitrile or ethylacetoacetate and different aliphatic and substituted aromatic aldehydes in the presence of ammonium acetate in ethanol. These multicomponent reactions were carried out both by solvent free grinding and by classical heating for comparison purposes. The catalytic activity of p-TSA (10 mol %) and guainidine HCl (5 mol%) in these reactions was tested over a set of aldehydes. Through catalytic screening, guainidine HCl (5mol%) at ambient temperature is proven to act as a very active catalyst for multicomponent reactions (MCRs) of 2-amino-4-phenyl-3-cyano-5-oxo-1,4,5,6,7,8-hexahydroquinoline derivatives and 2-methyl-4-phenyl-5-oxo-1,4,5,6, 7, 8- hexahydroquinoline-3-carboxylate in excellent yield up to 96% from aldehydes, 1,3-cyclohexadione, malanonitrile/ ethylacetoacetate and ammonium acetate. we develop an expedient multi-component synthesis of 2-amino-5-oxo-4-substituted phenyl-1,4,5,6,7,8-hexahydroquinoline-3-carbonitrile 4-4f and 2-amino-5-oxo-4-substituted phenyl-1,4,5,6,7,8-hexahydroquinoline-3-carboxylate 5-5l by using P-TSA under ultraviolet irradiation. Chemical reactions were carried out by the absorption of long-wavelength ultraviolet light by reactants to form product in a short period of time. We carried out the synthesis of polyhydroquinoline via irradiating the cyclohexanone/ cyclohexane dione/ dimedone with malononitrile/ethylacetoacetate and different aliphatic and substituted aromatic aldehydes in the prescence of ammonium acetate and P-TSA catalyst in ethanol assisted with ultraviolet light. The absorption of ultraviolet radiation by substrate allows a reaction to proceed by bringing the molecule to the activation energy, by changing the symmetry of the molecule and by changing the configuration of molecules. The reaction time is reduced from 1.5h to 4-5 min whereas % yield increased significantly by the ultraviolet assisted reactions. Thus, the superiority of the ultraviolet assisted protocol for the synthesis of polyhydroquinoline over thermal method had proved. Extensive biological studies on these v polyhydroquinolines with a variety of substitution patterns exhibit that these compounds have a mild potential of antimicrobial and antioxidant activities. Chalcones are secondary metabolites of terrestrial plants, precursors for the biosynthesis of flavonoids and exhibit various biological activities. A simple and regioselective synthesis of substituted 2-chloro-3-formyl quinolines through Vilsmeier-Haack cyclization of N-arylacetamide bearing an electron donating group at the meta position was carried out. Yields with electron donating groups were good in all cases. First, the chalcones were synthesized by direct Claisen-Schmidt condensation reactions between an equimolar quantity of quinoline-3-formaldehyde and different heterocyclic/aromatic ketones (a-i) by a base catalysed (40% NaOH solution) condensation. The 1H-NMR spectra of the synthesized compounds were in good agreement with the structures of the synthesized compounds. Extensive pharmaceutical studies in literature on various other quinolinyl chalcones indicate that these compounds have a significant potential of biological activity.