Aza-Michael Additions Of 2-Arylenemalononitriles With Indoles And 2-Aroylenones With Isatins

Aza-Michael addition is an important type of reaction featured high atom economy.It can be used to build C-N bonds in one step and to synthesize β-amino acids,β-lactams and heterocycles.In recent years the aza-Michael reactions based on indoles and isatins have attracted much attention.Indole is an important active group,which widely exists in the fine chemical products,for example,medicine,pesticides,perfumes,dyes and so on.Indole compounds also exist widely in nature.It is an important alkaloid that shows a variety of biological activities.At present,drugs containing indole structure have also been put on the market in large quantities,and have played a very important role in the treatment of human diseases.Isatin is found in the classic anti-cancer Chinese medicine Qingdai.It is also the lead compound of indorubin,a novel class I anticancer drug that is unique in China.It is also an endogenous heterocyclic molecule in human tissues.The modern research shows that isatin also has many biological activities,such as anti-convulsant,anti-epileptic,anti-Campinson’s disease,anti-aging,anti-cancer,antibacterial,antiviral,and blood lipid lowering activity.2-Arylbenzylidenemalononitriles are fine chemicals,which are synthetic raw materials for pharmaceutical vitamins and pesticides.Due to their superior performance,they plays a very important role in organic synthesis of pharmaceutical intermediates.Therefore the research for them is also gradually developed.In addition,2-aroylenones are structural units commonly found in natural products and medicinal chemistry,and often show a variety of biological activities.Because of their important biological value,research on 2-aroylenones is also one of the issues of interest to scientific researchers.Based on the above background,in this thesis,the aza-Michael addition reactions of indole with 2-arylenemalononitriles to synthesize N1 functionalized indoles,andthe aza-Michael addition reactions of isatins with 2-aroylenones to synthesize N1-functionalized isatins were investigated.These methods have the characteristics of convenient operation,mild conditions and high yield.This thesis is divided into three chapters:Chapter One:The aza-Michael addition reactions reported in recent years,the synthetic methods of indoles and isatins,and the synthetic methods of α,β-unsaturated dinitriles and α,β-unsaturated diones and their applications are reviewed.Chapter Two:The selective aza-Michael addition reactions of N-position of indoles to2-arylmethylenemalononitriles in the presence of potassium hydroxide were investigated,and a series of 2-[(1H-indol-1-yl)(aryl)methyl]malononitriles were synthesized.The salient features of this protocol are no transition metal catalyst,mild conditions,high regio-selectivity,high atom economy,high yield and simple work-up procedure.Chapter Three:In the presence of cesium carbonate,the aza-Michael addition reactions of the N1 position of isatins with 2-arylmethylene-1,3-diphenylpropan-1,3-diones were investigated,and a series of 1-(2-benzoyl-3-oxo-1,3-diphenylpropyl)indol-2,3-dione1-(2-benzoyl-3-oxo-1,3-diarylpropyl)indolin-2,3-diones were synthesized.The salient features of this protocol are no transition metal catalyst,mild conditions,high regio-selectivity,high atom economy,high yield and simple work-up procedure.