Synthesis Of The Key Intermediates Of Levofloxiacin And Synthesis Of ?,?-unsaturated Nitriles And Amides With N-hyroxyphthalimide As The Nitrogen Source

The thesis was divided into two parts.The first part mainly studied on the synthesis of the key intermediate of the levofloxacin.The second part mainly studied on the synthesis of?,?-unsaturated nitriles and amides by using N-hydroxyphthalimide?NHPI?as a new nitrogen source.The first part includes the first chapter and the second chapter:In the first chapter,the fluoroquinolones and the third generation of quinolones levofloxacin were introduced.Then the synthesis route of levofloxacin wasreviewed.Anovelprocessputforwardwithmethyl N,N-dimethylamino acrylate instead of ethyl N,N-dimethylamino acrylate for the first time,in order to avoid instability and the difficulty of preparation of sodium ethoxide.A detailed study of the hydrolysis steps in the new process route,replacing the acidic hydrolysis system with an alkaline hydrolysis system avoids large amounts of acidic wastewater and corrosion of the equipment.The study found that applying suitable conditions resulted in a yield of 98%for product,purity of 99.5%,and a critical impurity purity of less than 0.1%.The second part includes the third chapter and the fourth chapter.The third chapter introduces the extensive application of?,?-unsaturated nitriles in pharmaceutical chemistry,and summarizes the synthesis methods of?,?-unsaturated nitriles and the application of NHPI in organic synthesis.The fourth chapter innovatively proposes the synthesis of?,?-unsaturated nitriles and amides using?,?-unsaturated aldehydes and NHPI as raw materials,Pd?OAc?₂ as catalyst,and mechanism was discussed by conducting the control experiments.The feature of the method is convenient,simple and efficient.NHPI was used for the first time as nitrogen source to synthesize?,?-unsaturated nitriles and amides.It not only broadens the application of NHPI in organic synthesis but also provides new strategy for the synthesis of?,?-unsaturated nitriles in pharmaceutical chemistry research.