Study On The Synthesis Of Imidazo[1,2-a] Pyridines And Spiropyrrolidines

Imidazo[1,2-a]pyridine derivatives as an important kind of nitrogen-containingfused heterocycles which have the specific biological activity and structuralsimilarities with indoles, azaindole, have received great attention in medicine,agricultural chemical and dyestuff industry.The solvent-free reaction (SFR) is an important synthetic procedure from the viewpoint of green and sustainable chemistry. These approaches can help to reduce theamounts of undesired hazardous chemicals (including solvents) used, increase theselectivity towards the given products, and also enhance the rate of many organicreactions.Since1960s, biologists and pharmacologist discovered that spiro compounds havemake up a significant portion of biological active substances which were separatedfrom the nature. In addition, spiropyrrolidines also have pharmacological activitiessuch as antibacterial, anticancer, some with anti-leukemia, anticonvulsant, and localanesthesiaIn the first chapter, we briefly reviewed the synthesis and versatile applications ofβ-oxodithioesters, heterocyclic ketene aminals, imidazo[1,2-a]pyridine, andspiropyrrolidines; Then the advantages of several synthetic methods such assolvent-free reaction, multicomponet reactions (MCRs) in organic synthesis wereintroduced.In the second chapter, twenty-seven new1,2,3,5,6,7-hexahydroimidazo[1,2-a]pyridines and1,2,3,5,6,7-hexahydropyrido[1,2-a]pyrimidines were selectivelysynthesized by the one-pot three-component reactions of heterocyclic ketene aminals,β-oxodithioesters and aldehydes. The solvent-free was first brong in the reaction afterthe best reaction condition was determined: Et3N (1.0equiv) as a catalyst and EtOH assolvent. The reaction which avoid using of solvent, reduce the pollution to theenvironment and reduce the waste of energy and resources, fully reflect the requirements of green chemistry.In the third chapter, thirteen new spiropyrrolidines were synthesized by thereactions of ninhydrin,1,2-phenylenediamine, sarcosine, ethyl2-cyanoacetate andaldehyde. The solventhermal synthesis was firstly employed in the reaction after thebest reaction condition was determined: sarcosine (1.2equiv) and EtOH as solvent.The high atom economy and ecologically benign process are developed since only fourmolecules of water and one molecule CO2are lost; and multiple bonds andstereocenters are formed in a single reaction.Forty new compounds were synthesized, and the structures of all the syntheticcompounds were characterized by IR,1H NMR,13C NMR, and HRMS. Theunambiguous molecular structure of spiropyrrolidines and imidazo[1,2-a]pyridineswere determined by X-ray diffraction analysis.