Synthesis Of 2-oxindoles Via Intramolecular Cyclization Of N-arylamides

Oxindole derivatives exist widely in nature,most of them have biological activity and are widely used in medicines,pesticides,dyes,feed additives and other fields.Especially in the field of medicine,many drug molecules contain 2-oxindole structure.For example,Hosphine is a natural 2-oxindolone alkaloid,which originated in Malaysia,is isolated from the root of tree,has a certain analgesic effect.Indirubin,a natural alkaloid,is an effective component of anti leukemia drugs isolated from indigo naturalis,which has inhibitory effect on a variety of transplanted animal tumors.Another example is some synthetic 2-oxindoles derivatives:Sunitinib for gastrointestinal stromal tumors and metastatic renal cell carcinoma,Reserpine for lowering blood pressure and heart rate,Vincristine for lymphocytic leukemia,etc.Therefore,it is of great value to develop new methods for the synthesis of 2-oxindoles.At present,the synthesis methods of oxindole include Wolff rearrangement,metal catalyzed reaction,Gassman reaction,Friedel Crafts reaction and acid catalyzed rearrangement.In recent years,the synthesis of 2-oxindoles framework by intramolecular dehydrogenation coupling（IDC）has attracted much attention,such as electrochemical method,metal catalysis,DDQ oxidation,DTBP oxidation,iodine oxidation and high valent iodine oxidation.Based on our previous work,we would construct the framework of 2-oxindoles by IDC.In this paper,the IDC cyclization of N-aryl-β-carbonylamides catalyzed by iron/iodine was studied,and 2-oxindoles framework was constructed.In this method,Na₂S₂O₈ was used as oxidant,Fe（OAc）₂/Na I as catalyst,and the intramolecular dehydrogenation coupling cyclization of N-aryl-β-carbonylamides was realized through I^-/I₂ and Fe³⁺/Fe²⁺cycles,thus 2-oxindoles framework was constructed.The results showed that 3-anilino-2-alkyl-3-oxopropanoate containing fluorine,chlorine,bromine,alkyl,alkoxy,trifluoromethyl and cyano groups on the benzene ring could be successfully converted into 2-oxindoles in 18%to 77%yield.The reaction conditions were simple and easy to obtain,the post-treatment was easy,the separation yield could be as high as 77%,and the yield of most products was excellent.When the reaction was scaled up to gram level,the reaction yield was still maintained at 72%.The advantage of this method was that using stoichiometric iodine would greatly increase the cost.This method could achieve the same effect by using catalytic amount of iodine,reducing economic loss for industrial production.