Efficient One-Pot Synthesis of Spirooxindole Derivatives Containing 1,4-Dihydropyridine-Fused-1,3-Diazaheterocycle Fragments via Four-Component Reaction

Abstract

An efficient, one-pot synthetic protocol toward spirooxindole derivatives containing 1,4-dihydropyridine-fused 1,3-diazaheterocycle fragments, a class of biologically active compounds starting from 1,1-bis(methylthio)-2-nitroethylene, 1,n-diamine, isatin, or its derivatives, and malononitrile is described. The reaction proceeds in ethanol in the presence of 10 mol% of piperidine as a basic catalyst under reflux conditions to produce the title compounds in 74-85% yields.

Recent Progress on Routes to Spirooxindole Systems Derived from Isatin

“…With different Michael donors, diversely fused heterocycles with pyran or 1,4‐dihydropyridine moiety will be established. For example, the listed donors such as 3‐methyl‐1 H ‐pyrazol‐5(4 H )‐one , 4‐hydroxycoumarin , 4‐hydroxyquinolin‐2(1H)‐one and its N ‐allylic derivatives , cyclic 1,1‐enediamine , dimedone , 1‐(2‐phenylhydrazono)propan‐2‐one , β‐diketone or β‐ketoester , 2‐hydroxynaphthalene‐1,4‐dione , 3‐aminophenol , 2‐methyl pyrimidine‐4,6‐diol , 3‐methyl‐1 H ‐pyrazol‐5‐amine , naphthalen‐2‐amine , 1 H ‐indene‐1,3(2 H )‐dione , naphthalen‐2‐ol , and furan‐2,4(3 H ,5 H )‐dione are proved to be efficient for such protocol. Certainly, the suitable electron‐rich donors for such domino reaction are not limited to the aforementioned ones, and they can be reasonably extended to others with their functional group diversity.…”

Synthesis of Polyfunctionalized 1,4-Dihydropyridine-Fused-1,3-Diazaheterocycles: One-Pot Reaction of 1,1-Bis(methylthio)-2-nitroethylene, 1,n-Diamine, Arylaldehyde, and Malononitrile

“…As a part of our ongoing investigations aimed at expanding libraries of the aforementioned bioactive compounds and in continuing of our previous research on the one‐pot synthesis of spirooxindole derivatives containing 1,4‐dihydropyridine‐fused‐1,3‐diazaheterocycle fragments , we described here a four‐component reaction of 1,1‐bis(methylthio)‐2‐nitroethylene, 1, n ‐diamine 3 , arylaldehyde 4 , and malononitrile in ethanol as solvent and in the presence of 10 mol% piperidine as a basic catalyst under reflux to afford a series of 1,4‐dihydropyridine‐fused‐1,3‐diazaheterocycle derivatives in 60–75% yields (Table ).…”

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

“…203 A novel four-component reaction of isatins 1, 2-cyanoacetamide 160, cyclic 1,3-diketones 271 or 127 and alcohols was reported by Bazgir and co-workers (Scheme 110). 204 The reaction gave the unexpected spirooxindole ethyl carboxylates 272 and 273 in excellent yields and the spirooxindole carboxamide was not observed.…”