Green Synthesis Of β-amino Esters,Imidazopyridines And Pyridopyrimidin-4-ones Via Multicomponent Reactions

This thesis describes various green novel synthetic methodology by multicomponent reaction(MCRs)such as Mannich reaction,Groebke-Blackburn-Bienayme reaction and Conrad-Limpach type reaction,leading to several kinds of organic compounds such as βamino esters,imidazopyridines and pyridopyrimidine-4-ones with high efficiency and green manner.The formation of the β-amino estersand its mechanism have been further understood and studied with theoretical study.All products obtained have been investigated for biological activity and docking study which help in drugs discovery.The contents and results are as follows:Initially,a new efficient and simple method was designed for the synthesis of novel βamino ester derivatives by using the PPh3-catalyzed one-pot,three-component condensation from aryl amines,aryl aldehydes and dicarbonyl ester under solvent-free conditions.The comparative results from syntheses under these conditions provided a very simple reaction procedure that produced yields of 78-92%with high stereoselectivity.It also avoided column chromatographic separation and provided an easy aqueous work-up compared with the conventional reaction.To confirm and understand the origin of the stereoselectivity,densityfunctional theory(DFT)calculations were utilized to study the mechanism of the PPh3catalyzed Mannich reaction.Detailed analysis of the two-reaction pathway suggested that PPh3 plays an active role in the reaction and that it has a stereo-inductive effect on the Mannich reaction,favouring anti-isomer formation.All these synthetic novel β-amino estersderivatives were screened for antifungal and antibacterial activities but few of them gave desire biological activities,and they were further screened for hemolysis and cytotoxicity.Secondly,an efficient,silver-based catalytic system was designed for the synthesis of biologically important 3-aminoimidazo-fused heterocycles via the Groebke-BlackburnBienayme reaction,in which AgOAc was used as a catalyst and ethylene glycol as a solvent from isocyanides,various aryl aldehydes and 2-amino heterocycle.Good to excellent yields of 80-90%with high atomic economy and environmentally friendly conditions are the potential features of this one-pot process.These imidazole scaffold derivatives were tested for biological activities but unfortunately they were not highly active against antimicrobials.Finally,different derivatives of pyrido[1,2-a]pyrimidin-4-ones,a kind of heterocyclewith a wide range of biological activities and important moiety that many commercially available drugs possess,were synthesized via Limpach-type reaction by ethylene glycol-promoted cyclization of 2-amino pyridines with various β-oxo esters or alkynoates in good yields of 7888%.This reaction proceeded by nontoxic,cheap,environment friendliness and biodegradable solvent at the normal green atmospheric condition at low temperature.