Electrochemical Oxidation Of N-substituted Tetrahydroisoquinolines To Dihydroisoquinolinones

The construction of amide bonds is one of the most important organic chemical reactions.The universality of the amide structure can be shown in the compounds of proteins and many biomolecules.The direct oxidation of amines to lactams is an useful transformation.Dihydroisoquinolinone is a core structure in many natural products and biologically active compo unds.The traditional synthesis of dihydroisoquinolinones usually require multi-step reactions while the direct oxidation of tetrahydroisoquinoline to lactam could be more effcient.Compared with the traditional synthesis methods,the electrochemical synthesis methods have a few advantages: low material consumption,environmental friendliness,high atom utilization,and mild conditions.In this thesis,the direct oxidation of a tetrahydroisoquinoline to a dihydroisoquinolinone through an electrochemical method was investigated.A series of dihydroisoquinolinones were obtained by this procedure.This protocol provides an environmentally friendly and simple way for the construction of dihydroisoquinolinones with wide range of functional group in moderate to high yields,and lay the foundation for the research on the oxidation of N-substituted tetrahydroisoquinoline.It is divided into three charpters.In the first chapter,we reviewed the current research status of amides,especially the dihydroisoquinolinones,and summarized the synthesis methods of these compounds.Then we gave a brief introduction of the basic principles,types and advantages of electrochemistry.In the second chapter,we introduced the synthesis methods of the dihydroisoquinolinone by using electrochemical oxidation reactions.The experiment was conducted by using a potentiostat,and we used a carbon rod as the anode and a Pt plate as the cathode.According to the previous work in our laboratory,the by-product,dihydroisoquinolinone was found by using TLC method during the synthetic process of aminophosphonates.Subsequently,we extended of the reaction time and optimized the reaction conditions.Finally,86% yelid of dihydroisoquinolinone was obtained with N-phenyl-1,2,3,4-tetrahydroisoquinoline as a starting material,diethyl phosphite as a promoter,tetrabutyl ammonium p-toluenesulfonate as an electrolyte,5 m A current,dichloromethane as the solvent at 30°C.Next,we investigated the substrate scope of the reaction.First,we examined the substrate for the substituted N-phenyl group.We have tried to use methyl,halogen,trifluoromethyl,nitro,naphthyl and other substituents respectively.As a result,we found that weaker electron-withdrawing groups led to higher yield.Then we studied benzyl,acetyl,ester,pyridine and other groups as substituent.By examining the suitability of substrates,we have expanded the applicability of the reactions and laid the foundation for future work.The reaction mechanism was proposed.In the third chapter,detailed description of the electrochemical process,materials,equipments,the NMR spectrums were compiled.