Direct Electrochemical Oxidation Of Unprotected Secondary Amines And Phenols

With ongoing advancement of chemical synthetic methodologies,development of safe,environmental-friendly and energy efficient synthetic methods have attracted tremendous research attention.It is well-known that electricity is a clean and green energy source and chemical synthesis through electrochemical approaches have many advantages over traditional chemical synthesis,such as redox-agent free,mild reaction condition,controllable reaction progress,good selectivity and environment friendliness.Therefore,the specific electrochemical organic synthesis has recently witnessed a tremendous growth,leading to a variety of novel and unexpected means of transformations.Compared to conventional synthetic methods,the electrochemical strategy could also be conveniently employed to construct C-C,C-O,C-N,and C-S bounds even under more mild conditions.Dihydroisoquinolinone is a core structure in many natural products and biologically active compounds.?-amino phosphonates,which are mimics of amino acids,has broad pharmaceutical applications.Hydroquinone is an important fine organic chemical from petroleum industry.In this thesis,we have developed synthetic methodologies for these useful molecules using electrochemical approach,and the detailed content are listed as below:1.One-pot synthesis of dihydroisoquinolinone and its derivatives by electrochemical approach.In this part,we employed 1,2,3,4-tetrahydroisoquinoline(1a)and ethyl isocyanatoacetate(2a)to form dihydroisoquinolinone by electrochemical approach.Next,we studied the key factors that influence the transformation including electrolysis potential,types and amount of additive,the ratio of reagent,different solvent and so on.Under the optimized condition where a constant voltage of 6.6 V was applied to the reaction system,20 mol% K2CO3 and 1a:2a(1:2)were added into acetonitrile,67% isolated yield can be achieved.It can be known from control experiments and reported literatures that 1a and 2a were transformed to nitrogen-substituted tetrahydroisoquinoline at first,and then the intermediate was oxidized to nitrogen radical cation intermediate which further reacted with superoxide radical anion(reduced by cathodic process)to form desired product.2.Electrochemical approach for direct C-H phosphonylation of unprotected secondary amine.In this paper,we report a direct C-H phosphonylation of unprotected secondary amines via an electrochemical approach in the presence of catalytic carboxylate salt.We first studied the key factors that influence the transformation including additive,electrolyte,solvent,type of electrodes.Optimized condition was found out to be Li Cl O4 as electrolyte,Na OAc as additive,acetonitrile as solvent,carbon electrode as both anode and cathode electrodes,and 6.6 V of constant potential.This metal-free and exogenous oxidant-free method furnishes diverse target molecules including a series of cyclic and chain secondary amines with satisfactory yield under mild reaction conditions.Successful application of the protocol in a gram-scale experiment demonstrates the potential utility for further functionalization.Based on our synthetic and mechanistic investigations,a plausible reaction of anode oxidation pathway is summarized.3.Electrochemical catalytic oxidation of phenol to hydroquinone directly.In this section,we aim to develop a green,safe,and highly efficient electrochemical approach to oxidize phenol to hydroquinone directly without additional use of oxidant or nitration process.Several additives and electro-catalysts containing nickel or cobalt have been investigated.The primary study showed that catalyst containing cobalt could promote the electrochemical conversion of phenol to hydroquinone.In future study,the yield and selectivity could be improved by screening react condition and design of catalysts suitable for the system.