Study On The Synthesis Of N-arylindole-3-carbonitriles Via Intramolecular Oxidative Cyclization

N-Arylindole is an important heterocyclic compound. Its basic skeleton exists ina variety of medicinal active molecules. For example, Sertindole, clinically used totreat schizophrenia, contains the basic nuclear structure of N-arylindole ring.Although the synthesis of indole compounds has been reported largely in theliteratures, the report about the synthetic methods for N-arylindole, a special form ofindole substitution, is limited.On the basis of preliminary study which was the intramolecular oxidativecyclization to synthesize N-arylindole derivatives mediated by PIFA, we studied anew method for the synthesis of N-arylindole-3-carbonitriles via intramolecularcyclization.Using substituted phenylacetonitrile and akylcarboxylate as raw materials, aseries of2-aryl-3-oxonitrile derivatives could be synthesized. These compoundsreacted with substituted arylamines to prepare2-aryl-3-arylamino-2-alkenenitriles.And then the substrates were converted to N-arylindole-3-carbonitriles in a one-potmanner through NBS or NCS-mediated halogenation followed byZn(OAc)2-catalyzed intramolecular cyclization. Another C-N bond was built, and theN-arylindole skeleton was formed.Using this method, a series of N-arylindole-3-carbonitriles were synthesized. Thestructures of these derivatives have been determined by1H NMR,13C NMR and massspectrum. We also determined the structures of unstable intermediates, discussed andspeculated about the possible reaction mechanism.This method has some merit, such as inexpensive reagents, simple procedures,mild conditions and good to excellent yields. Because C-N bond was formed in thefinal step, benzene ring could be functionalized to achieve substitutedN-arylindole-3-carbonitriles before this process. Due to the above advantages, thismethod will play an important role in the synthesis of N-arylindole derivatives.