Decarboxylative Coupling Of ?-Keto Acids With Ortho-Phenylenediamines Promoted By An Electrochemical Method In Aqueous Media

Decarboxylative cross-coupling of carboxylate groups to construct new C-C bonds is a very important reaction in organic synthesis.2-Substituted benzimidazolesare important building blocks for pharmaceutical agents,natural products and functional materials.The conventional method for the synthesis of benzimidazoles involves the condensation of o-phenylenediamine with carboxylic acids or their derivatives in strong acids and high temperature,or the oxidative cyclization of imines derived from ortho-phenylenediamines with aldehydes in the presence of oxidants.As operational difficulties and harsh reaction conditions are often encountered in the existing methods,efficient methods for preparation of benzimidazoles under mild conditions are still in demand.In recent years,organic electrochemistry and aqueous-phase reactions haveattracted a great deal of attention,the development of aqueous phase electrochemical reaction is of practical significance.A brief review of recent development of decarboxylative cross-coupling of carboxylic acid to contruct carbon-carbon and carbon-heterobonds was presented in this thesis,and the research progress of 2-substituted benzimidazoles was also introduced.In connection with the previous synthesiswork of 2-substituted benzimidazoles and our interests in aqueous medium reactions,we considered to achieve the decarboxylation coupling reaction in aqueous phase via electro-organic synthesisThe project focuses on the optimization of reaction conditions.Current,electrode and solvent were explored by the controlled variable method,and the studies showed that in an undivided cell with platinum foils as anode and cathode,DMSO : H₂O?3/1,v/v?-0.2 M NH₄ClO₄ solutionas electrolyte,the reaction of ?-keto acid witho-phenylenediamine proceeded in excellent yield in the constant current.The reaction scope was explored by employing the optimized reaction conditions.The reactivities of various substituted aromatic diamines under our reaction protocol were examined,and most of the phenylenediamines,which bore electron-deficient or electron-rich groups on the aromatic rings,gave corresponding products in good to excellent yields.Besides the aromatic keto acid,the aliphatic keto acids underwent decarboxylative coupling with o-phenylenediamine smoothly to afford the desired benzimidazoles in moderate to good yields.Noteworthy,this method was extended to the synthesis of benzothiazoles and it was found that these useful compounds could also be synthesized in good yields.The mechanism of the reaction was studied in detail,and it was proposed that 2-substituted benzimidazoleswas produced from the decarboxylation and dehydrogenation of imine intermediates.