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Catalyst-Free One-Pot Three-Component Synthesis of 4‑Hydroxy-3-pyrazolylcoumarins in Ethanol at Room Temperature: Enolisable Aroylhydrazones as Efficient Ambident Nucleophile

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journal contribution
posted on 13.12.2019, 20:06 by Sayan Mukherjee, Animesh Pramanik
A sustainable and atom economic synthesis of biologically important 4-hydroxy-3-pyrazolylcoumarin derivatives via a catalyst-free one-pot three-component reaction of arylglyoxals, 4-hydroxycoumarins, and aroylhydrazones has been successfully achieved. Significantly, this green protocol embraces ethanol as a green solvent, a catalyst-free room temperature reaction, column chromatography/recrystallization free product isolation, high atom economy (up to 91.65%), low E-factor (up to 0.29 g/g), and gram scale product formation. Remarkably, this method has been successfully utilized for synthesis of polyheterocyclic 4-hydroxy-3-pyrazolylcoumarin derivatives containing up to five different heterocycles. Additionally, employment of arylhydrazones instead of aroylhydrazones in the above reaction produces a new class of biologically and pharmacologically important hydrazones bearing 4-hydroxycoumarin along with different aryls and heterocycles. Unlike arylhydrazones, aroylhydrazones exhibit keto–enol tautomerism, and the enolic form promotes efficient ambidentate nucleophilic attack which leads to facile formation of 4-hydroxy-3-pyrazolylcoumarin derivatives in mild and eco-friendly reaction conditions.