Study On Copper-Catalyzed Three-Component Synthesis Of Quinoline And Pyrazolopyrimidine Derivati

Nitrogen-containing heterocycles are important molecular structures and are widely found in natural products.Because of their special biological and physiological activities,they are widely used in medicines,pesticides,and functional materials.Therefore,it is of great significance to develop a facile and efficient method that substrate is cheap and easy to obtain,green and environmentally friendly,and has broad substrate scope.In this thesis,the research progress of quinoline and pyrazolopyrimidine derivatives was reviewed.Based on the preliminary work of the research group,a copper-catalyzed three-component synthesis of polysubstituted quinoline and pyrazolopyrimidine derivatives was developed.The main contents are as follows:1.Using p-methylaniline,styrene and DMSO as substrate to explore and optimize the reaction conditions,we found that the target product could be obtained in high yield when CuI was used as catalyst,1,10 phenanthroline was used as ligand and K₂S₂O₈ as an oxidant in DMSO at 120 ^oC for 12 h in an air atmosphere.Under the optimized reaction conditions,the scope range of the substrates was screened.The experimental results showed that the reaction exhibited wide substrate scope and good functional group compatibility.In general,the yield of aromatic amines with electron withdrawing groups is higher than those of aromatic amines with electron donating groups.It is worth noting that steric hindrance has a greater effect on the reaction.For styrene,whether it has an electron withdrawing group or an electron donating group on the phenyl ring,the yield is basically the same,that is,there is no obvious electronic effect,and similarly,the steric hindrance has a large influence.A plausible reaction mechanism was proposed based on control experiments and literatures.2.Copper-catalyzed three component synthesis of 5,7-diphenylpyrazolo[1,5-a]pyrimidine from3-aminopyrazole,benzyl alcohol and 1-phenylethanol.It was found that when Cu（OAc）₂ was used as catalyst,1,10-phen as ligand,KOH as base,at 110 ^oC for 18 h under an oxygen atmosphere,the corresponding target product can be obtained.This protocol exhibits wide substrate scope and good functional group compatibility.No obvious electronic effect on the two alcohols was found,but the steric hindrance has a greater effect on the reaction.27 corresponding products were obtained and characterized by ¹H NMR,¹³C NMR and HRMS.