Copper-catalyzed Synthesis Of Quinolinone And Pyrimido Quinolin Derivatives

This thesis is mainly about the development of novel synthetic strategies for the preparation ofquinolinones and pyrimido[4,5-b]quinolins. It includes the following two parts.In the first part, a novel synthesis of3-cyanoquinolin-2-one was explored and established. It wasfound that cyanoacetamide reacted smoothly with o-bromobenzyl bromide in the presence of K2CO3togive3-(2-bromophenyl)-2-cyano-propanamide in good yields. Upon treatment with CuI/K2CO3/L-proline,3-(2-bromophenyl)-2-cyano-propanamide underwent an intramolecular N-arylation and dehydrogenationcascade process to afford3-cyanoquinolin-2-ones with high efficiency.The second part of this thesis focuses on the synthesis of2-aminoquinoline-3-carboamides andpyrimido[4,5-b]quinolin-4(3H)-ones. Firstly, an efficient and convenient synthetic protocol toward2-aminoquinoline-3-carboamides through Cu(OAc)2catalyzed, K2CO3promoted one-pot three-componentreactions of the commercially available and economically sustainable2-bromobenzaldehydes,cyanoacetamides and aqueous ammonia is disclosed. More interestingly,2-bromobenzaldehydes couldreact readily with aqueous ammonia, cyanoacetamide and aldehydes under similar reaction conditions togive pyrimido[4,5-b]quinolin-4(3H)-ones in reasonably good total yields. It was noted that in this cascadeprocess, Cu(OAc)2is found to be not only indispensable for the coupling of aryl bromide with ammonia,but also crucial to the aromatization of the in situ formed2,3-dihydropyrimido[4,5-b]quinolin-4(1H)-one.In summary, some synthetically and biologically interesting heterocycles such as3-cyanoquinolin-2-ones,2-aminoquinoline-3-carboamides and pyrimido[4,5-b]quinolin-4(3H)-ones were synthesized byusing cyanoacetamide as a valuable starting material. Compared with literature methods toward theseheterocyclic compounds, the new synthetic methods presented here have advantages such as rapid reactionrate, simplicity of operator, mild conditions and high efficiency.