Preparation Of ?-X(X = Br Or Cl)Substituted Enamino Ketones/Esters

Enaminones/ enamino-esters compounds are the very important synthones for the synthesis of organic compounds and biologically active compounds.The enaminones/enamino-esters have both the nucleophilicity of enamines and the electrophilicity of ketene.Due to contain several substitutents,they can be used for various functionizations,and various chemical reactions can be occurred based on this double bond.The biggest structural features include containing multi-functional groups,many reactive positions and high reactivity of double bonds and their substituents due to the presence of electron-donating amine groups.At present,enaminones/ enamino-esters have been widely used in the syntheses of medicinal chemistry,organic chemistry,bioactive compounds and functional materials.Therefore,it is of great practical significance to develop more gentle,efficient and green methods to synthesize enaminones and their derivatives.In this thesis,a simple and economical method via multi-component two-step one-pot protocol is developed to synthesize various ?-substituted enamino ketones/ esters and deriatives.The development of this new strategy for organic synthesis has substantially achieved the safe,rapid,high-atom economics and economical steps to synthesize various ?-substituted enamino ketones/ esters which are the potential bioactive compounds.In this study,the multi-component two-step reaction was effectively blended into one pot and the target product could be synthesized in a good yield.The new organic strategy avoided the corresponding work-up operation of the first step reaction,so the cost of manpower and material resources in the preparation process was greatly reduced.The cost of preparation was saved and the generation of pollution was reduced.This is matched with the "green chemistry" concept.This paper mainly introduces the project in detail in the following four chapters:The first part mainly introduces the physical and chemical properties of enamino ketones/ esters compounds and the traditional methods of synthesizing enamino ketones/ esters compounds with the analysis of the advantages and disadvantages of various reaction strategies mentioned here.The application of enamine ketone/ester compounds in the construction of heterocyclic compounds and ring closure within molecules is summarized.The second part mainly introduces the suitable reaction system for the preparation of the corresponding ?-bromo substituted enamino ketones/ esters by the three-component two-step one-pot method with terminal alkynes,secondary amines and N-bromosuccinimide.In this reaction,the secondary amine first undergoes Michael addition with ?,?-unsaturated ketoesters to form the corresponding enamino ketones/ esters,and then the brominating reagent N-bromosuccinimide and catalyst(DABCO)are added to the above reaction system to produce ?-bromo substituted enamino ketones/ esters with good yields,Through this method,the substrate of amine group and the substrate of propiolate are expanded.Based on the three-component two-step one-pot reaction system developed successfully above,not only the preparation of the corresponding ?-bromo substituted enamino ketones/ esters can be achieved quickly and easily,but also the cost of the preparation of this type of compounds is greatly reduced by combining the two-step reaction into one pot successfully.In the third part of the thesis the less reactive chlorinating reagent N-chlorosuccinimide was successfully used in the above three-component two-step one-pot method to prepare ?-chloro substituted enamino ketones/ esters and successfully synthesized a series of compounds.The fourth part mainly introduces that the amine group in the enamino ketones/ ester which was preparated in the first-step amination is replaced by 2,5-dioxop-yrrolidin-1-yl group to produce 3-(2,5-dioxopyrrolidin-1-yl)acrylate via controlling the solvent.The succinyl group in 3-(2,5-dioxopyrrolidin-1-yl)acrylate can be further hydrolyzed to form the corresponding free amino group.Based on the relevant research,a multi-component two-step one-pot green method was finally developed to synthesize various related ?-X(X = Br or Cl)enamino ketones/ esters in good yields.And the selective preparation of the corresponding 3-(2,5-dioxopyrrolidin-1-yl)acrylate was achieved successfully by controlling the reaction solvent.