Novel and Efficient One-Pot Synthesis of Spiro[Indoline-3,4′-Pyrano [2,3-c]pyrazole]Derivatives Catalysed by L-Proline in Aqueous Medium

Abstract

An efficient mild one-pot synthesis of spiro [indoline-3,4'-pyrano[2,3-c]pyrazole derivatives by a four-component reaction of hydrazine, a β-keto ester, isatin, and malononitrile catalysed by L-proline in water is reported.

Proline and its Derivatives as Organocatalysts for Multi‐ Component Reactions in Aqueous Media: Synergic Pathways to the Green Synthesis of Heterocycles

“…Song and co‐workers illustrated a similar l ‐proline‐catalyzed four‐component reaction sequence that included the in situ formation of a pyrazolone intermediate and allowed the synthesis in high yields of structurally diverse spiro compounds 93 from hydrazines 92 , β‐dicarbonyl compounds 20 , isatins 84 and malononitrile 28 (Scheme ) employing l ‐proline as catalyst under aqueous conditions . The authors screened various catalysts (NaOH, Et 3 N, TBAF, p ‐TSA, CAN, FeCl 3 ⋅6 H 2 O and ZnCl 2 ) and solvents (ethanol, acetonitrile, DMF, ethyl acetate, DMSO and water) at different temperatures (room temperature, 40–100 °C) and identified that 10 mol% l ‐proline‐water at 80 °C was the best combination.…”

MgCl2 catalyzed one-pot synthesis of 2-hydroxy-3-((5-methyl-3-oxo-2-phenyl-2,3-dihydro-1H-pyrazol-4-yl)(phenyl)methyl)naphthalene-1,4-dione derivatives in EG

“…It is notable to mention here that after completion of the reaction, tautomerisation occurred in the pyrazolone rings of 5, which may exist in two tautomeric forms. Based on the X-ray crystal structure analyses in our previous work [18][19][20][21][22][23][24][25] and Tu's work 26 , it could be concluded that the desired products have two different structures: C=O form structure (Table 2, entries 5aa-5dc)…”

“…[11][12][13][14][15][16][17] It is promising that the integration of these two bioactive units into a single molecule may exhibit new or improved pharmacological properties.Considering the above points, and also in continuation of our interest on the synthesis of different kinds of heterocyclic compounds based on MCRs. [18][19][20][21][22][23][24][25] Herein we wish to report MgCl 2 as a low-toxic catalyst for one-pot synthesis of 2-hydroxy-3-((5-methyl-3-oxo-2-phenyl-2,3-dihydro-1H-pyrazol-4-yl)(phenyl)methyl)naphthalene-1,4-dione…”

A Green, Facile Approach for the Multicomponent Synthesis of Bioactive Spiro[Indoline-3,7′-Pyrrolo[1,2-c]Imidazole] Derivatives

“…As part of our ongoing efforts to explore environmentallyfriendly protocols for the construction of biologically important heterocyclic ring systems, [18][19][20][21] we now report for the first time, a one-pot three-component reaction which affords a series of novel spiro[indoline-3,7′-pyrrolo [1,2-c]imidazole] derivatives catalysed by NaHCO 3 in water. All the compounds were evaluated for CDC25B inhibitory activity subsequently.…”