Electrochemically Mediated C-C/C-N Bond Coupling To Synthesize 1-Naphthols,Polysubstituted Furans,N-Alkylazoles And Azo Compounds

C-C and C-N bond formation reactions are widely used in the synthesis of pharmaceutical molecules,agricultural chemicals,and complex molecules of important value in materials science.Therefore,the construction of C-C and C-N bonds has become an important research topic in organic synthesis.In recent decades,synthetic organic chemists have continued to develop new and more practical catalysts,as well as search for more environmentally friendly synthesis techniques for building C-C and C-N bonds.Among them,organic electrosynthesis can achieve selective redox conversion without exogenous oxidants and reductants through electron transfer on the surface of the electrode,and generally shows good functional group tolerance,thus providing an ideal strategy to construct C-C and C-N bonds.This thesis mainly studies the use of electrochemical anodic oxidation and cathodic reduction to replace traditional organic redox reactions,and the construction of C-C and C-N bonds through carbocation intermediates,carbon radical intermediates or nitrogen radical intermediates,thus various antitumor active compounds were synthesized succinctly and efficiently.The specific research contents are as follows:(1)Naphthol skeleton is ubiquitous in natural products and bioactive compounds,among which the multi-substituted 1-naphthols have a wide range of biological activities.We have developed a method to synthesize 1-naphthol compounds by using1,3-dicarbonyl compounds and alkynes as reaction substrates under constant potential electrolysis,through the carbon radical intermediate pathway,followed by the intermolecular[4+2]cyclization to construct C-C bond.The structures of these compounds were determined by X-ray crystallography experiments,and the mechanism of the reaction was verified by controlled experiments and cyclic voltammetry experiments.This electrochemical method uses cheap Cp₂Fe as the redox catalyst and H₂as the only by-product,thus avoiding the use of noble metal catalysts and oxidants.In addition,the method uses constant potential electrolysis to eliminate the effect of peroxidation of the reaction products by changing the reaction potential.This electrochemical reaction has the characteristics of environmentally friendly,broad substrate scope and good regioselectivity.(2)Furan is the core skeleton of many bioactive natural products,drug molecules and organic functional materials.Among them,polysubstituted furan derivatives are a kind of important heterocyclic compounds with various biological properties.In this study,we synthesized a series of novel tetrasubstituted furan compounds using1,3-dicarbonyl compounds and allenes as the reaction substrate,and low-cost ferrocene as the catalyst.Under the electrochemical conditions,the C-C bond was constructed,and the novel tetrasubstituted furan compounds were synthesized by indirect oxidation intermolecular cyclization.The structures of these compounds were determined by X-ray crystallography experiments,and the mechanism of the reaction was verified by controlled experiments and cyclic voltammetry experiments.The reaction is characterized by good functional group tolerance,high atomic economy and controllability,which provides a sustainable alternative synthesis strategy for the development of novel and valuable complex furan derivatives.(3)Azole compounds are the maximal family in pharmaceutical and pesticide chemistry,and the N-alkylazoles of five-membered nitrogen heterocycles are the important components and structural units of many bioactive molecules.We developed an electrochemically mediated C(sp³)-H azolylation reaction to synthesize sulfur-containing N-alkylazole compounds by constructing a C-N bond.The mechanism of the reaction was verified by controlled experiments and cyclic voltammetry experiments.This method has the advantages of environmentally friendly,simple operation,high atomic economy and easy control of the reaction process.(4)As an important nitrogen-containing compound,aromatic azo compounds are not only important synthetic colorants in the dye industry,but also used as indicators,radical reaction initiators,materials and food additives.We have developed a method to synthesize aromatic azo compounds using functionalized pyrrole or indole and aryl diazonium salt as the reaction substrate to construct C-N bonds under paired electrolysis conditions.The structures of these compounds were determined by X-ray crystallography experiments,and the mechanism of the reaction was verified by controlled experiments and cyclic voltammetry experiments.Paired electrolysis uses both anode and cathode reactions to synthesize the target compound,thereby avoiding the electricity costs required for the oxidation/reduction of sacrificial substances,achieving high atom economy and maximizing energy efficiency.(5)The antitumor activity of the synthesized various compounds was screened using MTT method.Most of the synthesized compounds had good inhibitory effect on tumor cells,while a few of them had good antitumor activity.For example,1-naphthol compound 1-3bl showed good antitumor activity against T-24 cells with IC₅₀value of9.0±1.0?M.The IC₅₀value of the polysubstituted furan compound 2-3da was 6.3±0.7?M,which showed a good antitumor activity against T-24 cells.Aromatic azo compound 4-3ea also showed good antitumor activity against T-24 cells with IC₅₀value of 1.5±1.3?M.Further studies on the antitumor mechanism of 1-naphthol compound 1-3bl showed that 1-naphthol compound 1-3bl could induce apoptosis of T-24 cells and inhibit tumor cell migration.