Synthesis And Antibacterial Activities Of Heterocvclic Compounds Via Multicomponent Reactions Of Isatins

The multicomponent reaction has becomed the hot spot in the field of organic and drug synthesis because of its high efficiency,atom economy,environment-friendly,simplified steps and efficient use of resources for nearly ten years.The skeleton of isatin has good bioactivity,many reaction points and become the high efficiency substrate.The spiro heterocyclic compounds have antibacterial,anticancer and insecticidal effect,which have been widely used in medicine,pesticides and dyes.In this dissertation,on the base of review MCRs,the methodologywasdevelopedbyusingisatinassubstrate.Spiro[indoline-3,5'-[1',2',4']oxadiazol]-2-ones,quinazoline-2,4-diones derivatives and spiro[indoline-3,2'-pyrrole]derivativesweresynthesizedandtheir antibacterial activity was tested.The specific research contents are as follows:Part I:A convenient and metal-free DMAP-catalyzed domino reaction of isatins,arylamines and hydroximoyl chlorides has been developed.we synthesized 22compounds of 3',4'-diaryl-4'H-spiro[indoline-3,5'-[1',2',4']oxadiazol]-2-ones in good to excellent yields under the optimization of 10 mol%4-dimethylaminopyridine?DMAP?as catalyst,Et OH as solvent at ambient temperature for 6 h.A possible mechanism of the reaction was proposed.The antibacterial activity of the desired compounds was tested with the 22 synthesised compounds;it was found that the compounds 2.4f,2.4j,2.4k,2.4l and 2.4v had the good antibacterial activity against Staphylococcus aureus.Part II:A green and highly efficient synthetic method for the synthesis of quinazoline-2,4-diones with hydrogen peroxide as the terminal oxidant via Baeyer-Villger oxidation has been developed.The 26 quinazoline-2,4-diones derivatives were synthesized under the optimization reactions of 30%H₂O₂ as oxidant,methanol as solvent,NaHCO₃?1.2eq?as the base at ambient temperature for 6 h.A possible reaction mechanism was proposed.The antibacterial activity of desired compounds was tested,it was found that the compounds 3.3o,3.3q,3.3r and 3.3w had good antibacterial activity against Staphylococcus aureus.Part III:A convenient catalyst-free method for preparing a series of spiro[indoline-3,2'-pyrroles]from three-component reaction of isatins,?-amino acid and phenylpropiolic acid esters in refluxing isopropanol with high regioselectivity and yields has been developed.The 27 novel spiro[indoline-3,2'-pyrrole]derivatives were synthesized in good to excellent yields and the effect of substrate on the reaction activity was investigated.The mediate yields were obtained used the acetylene ketone derivatives as substrate.A possible reaction mechanism for the reaction was proposed.The antibacterial activity of the desired compounds was tested,and the results showed that the compound 4.4f had good antibacterial activity against S.epidermidis,E.coli,Staphylococcus aureus and K.pneumonia.