Study On The Cyclization And Reduction Reaction Of Isatin To Construct Substituted Acridines And 2-Indolone

Isatin and its derivatives,as an important class of heterocyclic nitrogen compounds,have a variety of biological activities.In recent years,many reactions involving isatin have been carried out,including metal-involved reactions,acid-mediated reactions,oxidation reactions,ring expansion reactions,Friedel-Crafts reactions,substitution reactions,etc.Acridine has been widely concerned since its discovery.During the World War II,this compound was widely used in preservatives and antibacterial drugs.It has many biological activities,such as anti-cancer,anti-virus,anti-bacterial activities,and also many important applications in dyes and sensors areas.Therefore,it has been attracting much attention from organic chemists in the synthesis and application of acridine.This dissertation reports on two aspects of research work.In the first part,a trifluoromethanesulfonic acid-promoted cyclization esterification reaction of isatin,with hexafluoroisopropanol as solvent,was developed for the synthesis of substituted acridine compounds.The second part is to study the reduction reaction of isatin to produce 2-indolone and its derivatives.The following is the main content of this work:1.A CF₃SO₃H-promoted cyclization and esterification of isatin to synthesize substituted acridine compoundsWith the simple and readily available N-aryl isatin as raw materials,the CF₃SO₃H-promoted recyclization and aromatization reaction was developed to obtain acridine derivatives.The solvent of HFIP has a great influence on the reaction.This method has a wide range of tolerated groups.Twenty four substrates containing electron-withdrawing,electron-donating,and large conjugated systems,and eight nucleophilic reagents have been screened to afford the corresponding products in good yields.In terms of application of this method,two precursors of bioactive molecules acetylcholinesterase inhibitor 2 and BOCMAT-6 were synthesized with a short synthetic route.At the same time,four derivatization reactions were carried out.In addition,the photophysical properties of these synthesized acridines were investigated,demonstrating that several heterocyclic acridines was obtained at a high quantum yield.2.A CF₃SO₃H-promoted reduction of isatin with thiol to produce 2-indolone and its derivativesBased on the previous work,we developed a metal-free,mild reduction reaction of isatin to obtain 2-indolone with mercaptan and CF₃SO₃H as effective reagents.Compared with the classic carbonyl-reduction methods,this reaction condition is mild without any metal reagents.Many functional groups are highly tolerated,which meets the requirements of green chemistry.By screening the reaction temperature,a product in which the 3-carbonyl group of isatin is replaced by thiol can be generated.Twenty one substrates for the substitution reaction and seventeen substrates for the reduction reaction were screened to afford the corresponding compounds in excellent yields.The reduction product 2-indolone is an important drug intermediate.For example,it is an important precursor of the synthetic drug ropinirole.This reaction is simple and the reaction conditions are mild,without any metal,especially useful for the synthesis of related drug molecules.