Base On Copper-catalyzed And Animated Synthesis Of Quinoline And Quinazoline

As important nitrogen-containing heterocycles, quinolines and quinazolines not only exist widely innature, but also present frequently in pharmaceuticals and other biologically and physiologically activemolecules. Therefore, the search for more convenient and effective methods to synthesize quinolines andquinazolines is an important task in synthetic chemistry. Meanwhile, copper catalyzed coupling and relatedtandem reactions are emerging as a powerful tool in organic synthesis and have found extensiveapplications in the construction of N-heterocyclic skeletons owing to their simple operation process, mildreaction conditions, and high efficiency. Inspired by these results, this thesis proposed and established somenew synthetic approaches toward quinoline and quinazoline derivatives via copper catalyzed amination andrelated tandem reactions by using aqueous ammonia as the nitrogen source. It mainly includes thefollowing two parts:Firstly, a copper-catalyzed one-pot multi-component reaction of2-bromobenzaldehyde, acetophenoneand aqueous ammonia was studied. Through exploration of the effect of different solvents, copper salts,bases, reaction temperatures and ligands on this reaction, the optimum conditions for the formation of2-phenylquinoline were obtained. Based on the optimized reaction conditions, the scope and generality ofthis novel reaction was also studied and it was found that2-bromobenzaldehydes and acetophenonesbearing various substituents took part in this reaction smoothly, thus resulting a simple, efficient andeconomical new method for the preparation of2-arylquinolines.Secondly, a copper-catalyzed one-pot multi-component reaction of2-bromobenzyl bromide,benzaldehyde and aqueous ammonia was studied. Through exploration of the effect of different solvents,catalysts, reaction temperatures and ligands on this reaction, the optimum conditions for the formation of2-phenylquinazoline were obtained. Based on the optimized reaction conditions, a series of quinazolinederivatives with different substitution patterns were successfully prepared with good efficiency fromvarious substrates. In further study on the scope and generality of this reaction, methylamine andethylamine were found to be also suitable substrates for this tandem process and from this reactiondiversely substituted1,2,3,4-tetrahedroquinazolines were synthesized with high yields.In short, novel methods for the preparation of nitrogen-containing heterocycles such as quinoline,quinazoline and1,2,3,4-tetrahedroquinazoline derivatives via copper catalyzed amination and relatedtandem reactions by using aqueous ammonia as an economical and easily obtainable nitrogen source havebeen developed. Compared with literature methods, these new synthetic protocols have such advantages ascheap and easily obtained starting materials, simple synthetic procedures, mild conditions, and highefficiency.