One-Pot, Pseudo Five-Component Synthesis of Spirooxindole Derivatives Containing Fused 1,4-Dihydropyridines in Water

Abstract

An efficient, facile, and simple route for the preparation of spirooxindole-containing fused 1,4-dihydropyridine derivatives through a one-pot, pseudo five-component condensation reaction of isatin or its derivatives, 1,1-bis(methylthio)-2-nitroethylene, 1,3-dicarbonyl compounds, and two equivalents of ammonia in water is reported. The merits of this method include the use of water as a green solvent, and inexpensive and easily available starting materials and catalyst, the high yield of products, and the straightforward work-up.

Pseudo-multicomponent reactions

“…In the same year, a series of spirooxindoles were prepared from a pseudo-5CR by Alizadeh and co-workers, 72 comprising the reaction of two equivalents of ammonia 419 , 1,1-bis(methylthio)-2-nitroethylene ( 420 ), isatin (or derivatives) 422a–f and 1,3-dicarbonyl compounds 423a–b in water as solvent. A plausible reaction mechanism was proposed for this reaction as illustrated in Scheme 44.…”

Synthesis of spiro-fused heterocyclic scaffolds through multicomponent reactions involving isatin

“…205 A previously unknown class of highly substituted pyrazoline-spirooxindoles 277 was prepared by an uncatalyzed approach incorporating a domino nucleophilic substitution / condensation / aza-ene addition cyclization reaction sequence. 1,1-Dihydrazino-2-nitroethylene 275, which was generated in situ from the nucleophilic substitution reaction of hydrazine 130 and 1,1-bis(methylthio)-2-nitroethylene 269, was isolated and allowed to condense with isatins 1 followed by an intramolecular aza-ene addition cyclization (Scheme 112).…”

Part II: nitroalkenes in the synthesis of heterocyclic compounds

“…A one-pot procedure for synthesis of spirooxindolecontaining fused 1,4-dihydropyridine derivatives 52 were reported by Alizadeh et al via a pseudo ve-component condensation reaction of isatin or its derivatives 50, 1,1bis(methylthio)-2-nitroethylene 49, 1,3-dicarbonyl compounds 51, and two equivalents of ammonia 48 in the presence of 10 mol% p-toluenesulfonic acid (PTSA) in water (Scheme 12). 30 1,3-Cyclohexanedione, 5,5-dimethyl 1,3-cyclohexanedione, and 1,3dimethylbarbituric acid were successfully used as a 1,3-dicarbonyl compound. According to the proposed mechanism by the authors, the reaction initiated with the addition of ammonia to 49 to give the corresponding enamine, followed by the Stork enamine alkylation of the prepared enamine with in situ prepared Knoevenagel product from 50 and 51.…”