Na2S2O4 mediated intramolecular tandem reductive cyclization of N-(2-nitroaryl)-2-oxo-2-arylacetamides to the synthesis of 3-arylquinoxalin-2(1H)-ones

Amines are generally prepared from their corresponding nitro compounds by reduction. The question is whether nitro compounds can be used directly in place of amines in any synthetic transformation. While in-situ reduction of nitro compound to amine could have a significant advantage, the challenge would be how to integrate the reduction coupled with a subsequent synthetic transformation without isolation of amine especially in the presence of one reducing agent. Sodium dithionite (Na 2 S 2 O 4 ) is an inexpensive, green and one-electron reductant, which has recently gained recognition not only in the chemoselective reduction of nitro to the amino group, but also coupled with another synthetic transformation. To further expand the scope of this tandem reductive synthetic transformation, we report herein a Na 2 S 2 O 4 mediated intramolecular tandem reductive cyclization of N -(2-nitroaryl)-2-oxo-2-arylacetamides to the synthesize 3-arylquinoxalin-2(1 H )-ones. The substrates were prepared using our previously reported method from arylglyoxals and ortho -nitroanilines in the presence of TBHP and a catalytic amount of iodine. The reductive cyclization of N -(2-nitroaryl)-2-oxo-2-arylacetamides proceeds through a sequential chemoselective reduction of nitro group followed by condensation of the amino group, generated in-situ , with the ketone group attached to the aryl ring. The two reactions occur in a tandem fashion exclusively in the presence of Na 2 S 2 O 4 producing only sodium bisulfite as the only inorganic waste in this reaction. The method is operationally simple, avoids purification by column chromatography, exhibits a wide substrate scope, and has the ability for late-stage modification of the synthesized molecules. Unlike the previous reports, the strategy is substantially different overcoming limitations in the prior arts.