Electrochemical Synthesis Of Selenomethyl-substituted Cyclic Ethers Or Lactones,gem-Bisarylthio Enamines,Quinazolinones,Esters

Organic electrochemistry is a green synthetic tool,which employs electron as reagents to achieve redox reactions.Under these exogenous-oxidant-free and exogenous-reductant-free conditions,the reaction costs are reduced and the by-products are reduced.In the past decades,organic electrosynthesis has made tremendous research progress,which includes the construction of various chemical bonds,the synthesis of high value-added organic products and various heterocyclic compounds,and the realization of arylation reactions,etc.In addition,other fields in electrochemistry are also flourishing and have achieved fruitful results,such as: flow electrochemistry,the design of various media and electrodes.In this thesis,we focus on the study of electrochemical mediated dehydrogenation coupling reaction for synthesis of selenocyclic ethers and lactones,gem-bisarylthio enamines and ?-phenylthio ketones,quinazolinones and esters.A series of multifunctional compounds have been obtained under mild reaction conditions using electrons instead of traditional redox agents.This thesis is divided into five chapters:Part I: The research progress of organic electrochemical dehydrogenation coupling reactions and its applicationOrganic electrosynthesis employs electricity instead of chemical reagents to drive the redox process,providing a mild and effective alternative to traditional redox reactions.This technology is highly controllable,which the reaction rate and chemical selectivity can be controlled by adjusting the current or voltage.In this chapter,we mainly describe the research results of the organic electrochemical dehydrogenation coupling reaction in anodic oxidation,including the construction of various chemical bonds(carbo-carbo and carbo-heteroatom bonds),the realization of olefin bifunctionali-zation,and the synthesis of bioactive heterocyclic compounds.At the same time,some problems existing in organic electrochemical synthesis and the future development trend are also introduced.Part II: Electrochemical difunctionalization of olefines: access to selenomethyl-substituted cyclic ethers or lactonesOrganoselenium compounds have a wide range of biological activities,such as anti-tumor,cardiovascular protective,anti-pathogenic microbial,immunomodulatory,and neuroprotective effects.Therefore,it is of great significance to introduce selenium into organic compounds.The traditional synthetic methods of organic selenides include transition metal catalysis,photocatalysis,etc.However,these methods usually suffer from noble metal catalysts or photosensitizers,and often produce metal residues.In addition,excessive oxidants are often required in many strategies,which not only increase economic costs but also easily cause a variety of by-products.Herein,we report a metal-and oxidant-free electrochemical method for preparing selenomethyl-substituted cyclic ethers or lactones via difunctionalization of olefines.It is a green synthesis method because of its convenient operation,cheap and readily available reaction substrates,electrons as the oxidant,and a catalytic amount of ammonium iodide as the catalyst and electrolyte.A series of mid-ring selenocyclic ethers(especially 9,11-membered rings)and selenolactones can be obtained through this strategy.The control experiments show that the reaction is carried out by ion pathway.Moreover,this reaction has the advantages of broad substrate scope,good functional group tolerance and mild reaction conditions.Part III: Electrocatalytic synthesis of gem-bisarylthio enamines and ?-phenylthio ketones via a radical process under mild conditionsgem-Dialkenes are important and useful building blocks for chemo-and regioselective synthesis of multisubstituted alkenes and heterocycle.At present,the synthesis of gem-dialkenes mainly depends on transition metal catalytic,and the common gem-dialkenes include gem-dihalogenalkenes and gem-diborylalkenes.There are few reports of gem-bisarylthioalkenes,and only two cases have been reported so far.However,the reported methods have some limitations,such as long reaction times and the need for strong base or nitrogen protection.We herein firstly describe an efficient electrochemical method of achieving gem-bisphenylthio enamine and ?-phenylthio ketones from alkenyl azide in mild conditions.It is shown that the electronic properties of substituted groups on the alkenyl azidyl ring are very important to the product.gem-Bisphenylthio enamines are obtained when a strong electron withdrawing group on the benzene ring of the vinyl azides,while ?-phenyl thioenones are obtained when a weak electron withdrawing group or an electron-donating group the benzene ring of the vinyl azides.EPR experiments and control experiments show that the reaction is carried out through the free radical pathway.This protocol features metal-and oxidant-free materials,broad tolerance of substrates,and mild reaction conditions.Part IV: Electrochemical synthesis of quinazolinones via the metal-free and acceptor-free dehydrogenation of 2-aminobenzamidesQuinazolinones are an important class of nitrogen-containing heterocyclic compounds that have broad pharmacological activities such as antibacterial,anti-inflammatory,anticonvulsant,anticancer,anti-HIV and analgesic activities.Traditionally,quinazolinones are generally prepared by 2-aminobenzamide with aldehydes,carboxylic acids,acyl halides aldehydes or ketones,etc.,which rely on transition metal catalysis or stoichiometric oxidants.Therefore,the development of a new method to synthesize quinazolinone under mild conditions is still highly desirable.In this chapter,we report an electrochemical synthesis method for the synthesis of quinazolinones by metal-and acceptor-free dehydrogenation coupling.Control experiments and cyclic voltammetry studies have shown that tht target products can be obtained through the selective anodic dehydrogenative oxidation/cyclization of 2-aminobenzamide and benzyl chloride at the anode.Part V: Electrochemistry-induced esterification of aldehydes with alcohols via anodic oxidationEster is a ubiquitous group in natural products and medicines,as well as one of the most important and abundant functional groups commonly found in organic synthesis.It is often used to synthesize the building blocks and protective groups of biologically active compounds.The classical synthesis of esters is based on the esterification of carboxylic acids with alcohols.The directly dehydrogenation coupling of aldehydes and alcohols is much more attractive because of it is a more atomically economical method.At present,these methods are mostly carried out under noble metal catalysts,NHC catalysts,photocatalysis conditions.Therefore,it is of great significance to develop a greener and milder strategy to synthesize ester compounds directly through the dehydrogenation coupling of aldehydes and alcohols.In this chapter,we report an efficient method for synthesizing esters from aldehydes and alcohols in a constant current mode.This process is distinguished by simple operation,mild reaction conditions,and cheap and readily available raw materials.Control experiments show that aldehydes and alcohols are firstly oxidized to acetals and follow by the oxidation and deprotonation at the anode to produce esters.