‘Solvent-free’ and ‘on-solvent’ multicomponent reaction of isatins, malononitrile, and bicyclic CH-acids: fast and efficient way to medicinal privileged spirooxindole scaffold

Abstract

The fast (15 min) PASE-'solvent-free' and 'on-solvent' multicomponent reactions of isatins, malononitrile and bicyclic CH-acids catalyzed by sodium acetate result in efficient formation of substituted spiro-oxindoles in 90-98% yields. These methods are fast multicomponent approaches to the spiro-oxindoles, substances with promising anticancer activities. These new 'solvent-free' and 'on-solvent' techniques reduce solvent use, thereby leading to reduced waste, in connection with a new concept of solvent-assisted domino-reaction strategy.

6′-Amino-5,7-dibromo-2-oxo-3′-(trifluoromethyl)-1′H-spiro[indoline-3,4′-pyrano[2,3-c]pyrazole]-5′-carbonitrile

“…We previously carried out a multicomponent transformation of isatins, malononitrile, and different C-H acids into functionalized spirooxindoles [15][16][17][18]. These reactions were carried out both in solution and in 'on-solvent' and 'solvent-free' formats.…”

Green multicomponent approach to novel 5‐[(2H‐Pyran‐3‐yl)(aryl)methyl]‐1,3‐dimethylpyrimidines

“…Initially, to examine the reactions of benzaldehyde 1a, 1,3-dimethylpyrimidine-2,4,6(1H,3H,5H)-trione and 4-hydroxy-6-methyl-2H-pyran-2-one, we have carried out the multicomponent synthesis of [(2H-pyran-3-yl)(phenyl)methyl]-1,3-dimethylpyrimidine 2a in solvent-free conditions (Scheme 1, Table 1, Entries 1, 2) [19][20][21][22]. Under these conditions, the result was unsatisfactory.…”

Engaging Isatins in Multicomponent Reactions (MCRs) – Easy Access to Structural Diversity

“…This interesting solvent free protocol uses isatin derivatives, malononitrile and three analogous bicyclic C−H acids: 4‐hydroxy‐2 H ‐chromen‐2‐one, 4‐hydroxyquinolin‐2(1 H )‐one and 4‐hydroxy‐1‐methylquinolin‐2(1 H )‐one (Scheme 48A). Despite moderate substrate scope, the reaction is very fast, plus it is solvent‐free [94] . Following the same concept, the group of Bagchi et al .…”

“…NEt 3 [56] DBU [58] Na 2 CO 3 [61] DMAP [62] DABCO [81] , [82] , [85] , [157] C 4 (DABCO) 2 .2OH [83] NaOAc [94] , [66] , [110] urea [95] TEA [111] CsF [113] …”