Cu(?)-catalyzed Multi-component Reaction: Diversified Synthesis Of Imidazo[1,2-a]pyrimidine And Imidazo[2,1-b]thiazole

Fused heterocyclic compounds are key structural scaffolds in a broad variety of natural products and drug molecules.Among them,pyrimido[1,2-a]benzimidazoles and imidazo[2,1-b]benzothiazoles have been related to an extensive range of biological and pharmacological activities,such as anticancer,antibacterial and antianxiety.Moreover,these kinds of compounds have also been widely used in dyes,multifunctional materials,fluorescent probes and other technological fields.In this thesis,we developed a straightforward method for the diverse synthesis of 2,3-,2,4-disubstituted imidazole[1,2-a]pyrimidines,2,4,10-trisubstituted imidazole[1,2-a]dihydropyrimidines and imidazole[2,1-b]thiazoles using aldehydes,azines and easy-storage and-operation acetylene acids as the starting materials and CuI as the catalyst.We found that under the optimal conditions,when the heteroatom in 1-position of azines is sulfur,this multicomponent reactions(MCRs)would experience a 5-exo-dig cyclization to form the imidazole[2,1-b]thiazole skeleton,however,when the heteroatom in 1-position is nitrogen,the MCRs would experience a 6-endo-dig cyclization to form the imidazole[1,2-a]pyrimidine skeleton.More interestingly,when using propiolic acid,aromatic aldehyde and 2-aminobenzimidazole as the reacting substrates,2,3-disubstituted pyrimido[1,2-a]benzimidazoles could be obtained in moderate yields.To the best of our knowledge,one-pot methods for completing the assembly of the pyrimido[1,2-a]benzimidazole scaffold and its C-3 position functionalization in a cascade process hasn't been reported yet.Notable features of this new approach include readily available starting materials,easy-storage and-handling alkyne sources,common and inexpensive catalysts,convenient operations,and no need for isolating the intermediates.The reaction should therefore have widespread applications in the rapid construction of various complex heterocyclic compounds,which play significant roles in medicine,materials and other important fields.The main contents of this study are as follows:1.The MCRs of 2-aminobenzimidazole,aldehydes and benzene propiolic acid were first evaluated.After extensive exploration of the reaction conditions including the catalyst,the additive,the solvent,and the reaction temperature,the optimal conditions were finalized with the 2-aminobenzimidazole,aldehyde(1.2 equiv),propiolic acid(1.2 equiv),Cul(10 mol%)and K2CO3(1.2 equiv)in DMSO at 110?.Under the optimal conditions,a series of substrates were investigated.It was found that various aromatic,heteroaromatic,polycyclic aromatic as well as aliphatic aldehydes were well tolerated for this one-pot transformation and furnished the corresponding 2,4-disubstituted imidazole[1,2-a]pyrimidines in practical yields.In addition,when the N1-position of 2-aminobenzimidazole is alkyl substituent,2,4,10-trisubstituted benzene[d]imidazole[1,2-a]dihydropyrimidine could also be obtained in good yields.2.When propargylic acid,aromatic aldehyde and 2-aminobenzoimidazole were employed in the MCRs,novel 2,3-disubstituted imidazole[1,2-a]pyrimidine compounds were achieved for the first time.Through further screening of the reaction conditions,the optimal conditions for forming this new kind of compounds was determined with the azine,aldehyde(2.1 equiv),propiolic acid(1.2 equiv),CuI(10 mol%)and K2CO3(1.2 equiv)in DMSO at 110?.A series of substrates have been extended under the optimal conditions and the results were listed in Table 3-6.3.When the azine component is 2-aminobenzothiazole,the reaction could also performed smoothly,however,imidazole[2,1-b]thiazoles,the formation of which involved 5-exo-dig cyclization,were obtained in moderate yields.4.In order to explore the reaction mechanism,we conducted a series of control experiments.Based on the preliminary results and the literature reports,a possible mechanism was proposed.5.The ion sensing property of our synthesized imidazole[1,2-a]pyrimidines was also explored,and the results indicates that some compounds,such as 1m,are suitable candidates as selective fluorescence sensors for metal ion Fe3+.