Mechanically Activated Heck And Oxdative Heck Coupling Reactions Applied To The Synthesis Of Heterocyclic Aromatic Compounds

The development of organic synthesis has been deeply rooted in the lives of the modern society in all aspects nowdays,in which the synthesis and application of drugs is the most indispensable one.The chemists always hope to find a convenient,high-efficient and eco-friendly synthetic route as a new research direction whether the synthesis of new compounds or the old ones.Mechanochemically activated ball-milling reaction,which was applied into various organic syntheses,has become the new-aged focus to the chemical researchers as a developing,solvent-free synthetic method.In this dissertation,investigations are focused on the Heck and Oxidative Heck coupling reaction under mechanical milling condition.The main contents include the following aspects:(1)The description of the development of the mechanical chemistry,the overview of mechanical milling in organic syntheses as well as various related factors.(2)On the basis of the overview of Heck coupling reaction,under mechanical milling conditions,using Pd(OAc)2/TBAB as catalytic system,K2CO3 as solid base,silica gel as grinding auxiliary to synthesize a series olefin substituted five-membered heterocyclic aromatic compounds quickly and solvent-freely,and further applied the mechanically activated Heck reaction into the green synthesis of the key intermediate of antiasthmatic drug: Montelukas.Compared with traditional Heck reaction in the solvent conditions,the mechanically activated Heck reaction possessed a lot of outstanding virtues such as short reaction time,high yields and wide generality,and the grinding procedure successfully avoid to use toxic organic solvents which were labeled as the accordance of "Green Chemistry".(3)Under mechanical milling conditions,using Pd(OAc)2 and PdCl2 to catalyze the oxidative Heck reaction between indoles and acrylates.Mechanical milling technique has been first applied to the oxidative Heck coupling in our study:(1)Using Pd(OAc)2 as catalysts,non-activated MnO2 as oxide and with the help of liquid assistant grinding technique,the oxidative Heck reaction were carried out smoothly and synthesized a serious of 3-alkenyl indole derivatives.(2)Using Pd(OAc)2 as catalysts,MnO2 as oxide to yield the ?,?-diindolyl propionates with potential biological activities under mechanical milling conditions.Subsequently,we utilized ESI-MS technics to study the reaction mechanisms under mechanical milling conditions.The unstable intermediate which can not be existed in traditional solution reaction has been captured under mechanical milling conditions,and that‘s provided potent technical support for the mechanical milling reaction mechanisms.(4)Under mechanical milling conditions,using Pd(OAc)2 to catalyze the oxidative Heck reaction between furanes/thiophenes and acrylates,and synthesize a serious of furanes/thiophenes derivatives with potential biological activities under mechanical milling conditions.This conversion broadens the application of mechanical milling technics and possessed the characteristics,like short reaction time,operation convenience and fast post processing.In summary,this dissertation successfully using mechanical milling technic to synthesize a series of allyl-substituted heterocyclic aromatic compounds through Heck coupling and oxidative Heck coupling,and broaden the application of the mechanical milling technic in organic synthesis effectively.