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

Journal Article (Journal Article)

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.

Full Text

Duke Authors

Cited Authors

  • Mukherjee, S; Pramanik, A

Published Date

  • January 13, 2020

Published In

Volume / Issue

  • 8 / 1

Start / End Page

  • 403 - 414

Electronic International Standard Serial Number (EISSN)

  • 2168-0485

Digital Object Identifier (DOI)

  • 10.1021/acssuschemeng.9b05682

Citation Source

  • Scopus