Unexpected cyclization of ortho-nitrochalcones into 2-alkylideneindolin-3-ones

Abstract

Highly efficient cascade involving Michael addition and Baeyer–Drewson reaction is triggered by cyanide anion and transforms ortho-nitrochalcones into 2-(3-oxoindolin-2-ylidene)acetonitriles.

Oxidative Cyclization of 4-(2-Aminophenyl)-4-oxo-2-phenylbutanenitriles into 2-(3-Oxoindolin-2-ylidene)acetonitriles

“…The indoline nitrogen in acetonitrile 1 is originated from the nitro group when obtained via the original method. 17 Since this involves reduction of the N–O bond in cyclic nitronate 5 , it is hardly possible to derivatize it directly into anything but an N–H bond, especially under acidic conditions. Therefore, installation of other substituents at this position to access derivatives 7 would involve additional steps in the synthetic sequence.…”

“…All physical data were identical to those previously described. 17 R f 0.65 (EtOAc/Hex, 1:1). 1 H NMR (400 MHz, DMSO- d 6 ) δ 10.49 (br.…”

“… 16 Recently, we have communicated on the unexpected formation of 2-alkylideneindolin-3-ones taking place upon treatment of ortho -nitrochalcones with potassium cyanide and acetic acid in methanol. 17 It was shown that conjugate addition of KCN to chalcone 3 triggers intramolecular attack of nucleophilic enole moiety in 4 , leading to the formation of intermediate cyclic nitronate 5 ( Scheme 2 ). Upon addition of AcOH, the emerald-green compound could be reduced into an orange-red conjugated nitrile 1 ( Scheme 2 ).…”

“…Upon addition of AcOH, the emerald-green compound could be reduced into an orange-red conjugated nitrile 1 ( Scheme 2 ). 17 However, this attractive and simple method had serious limitations, permitting access only to indolines with non-substituted nitrogen atoms. Herein, we report on the development of a more general and efficient synthetic method to address these issues.…”

Synthesis, Crystal Structures, and Molecular Properties of Three Nitro-Substituted Chalcones

“…We found that the chalcone with the nitro group at the ortho position develops the strongest anti-inflammatory protective effect, whereas the chalcone with the nitro group at the para position, showed the smallest effect [14]. Another important aspect of Crystals 2021, 11, 1589 2 of 12 some nitro chalcones is that they can be used as intermediates for synthesizing various heterocyclic compounds like indoles, thioaurones, carbazoles, sultams, benzothiophenes, quinolines and indolin-3-ones [15][16][17][18][19][20][21][22][23]. On the other hand, the nitro chalcones also find application as chemosensors for anion sensing [24].…”