P₄O₁₀/TfOH-mediated metal-free synthesis of 4-hydroxycoumarins and a one-pot strategy to build their hybrids

Abstract

4-Hydroxycoumarins are among the most versatile heterocyclic scaffolds, and they are extensively used in the synthesis of a wide range of chemical molecules. Because of their biological and pharmacological effects, 4-hydroxycoumarin-based compounds are important among heterocyclic structures. In this study, a new method is developed to synthesize 4-hydroxycoumarins using a phosphoric anhydride and trifluromethanesulfonic acid (P₄O₁₀/TfOH) reagent system without the employment of either a catalyst or solvent. The direct condensation of phenols with malonic acid at ambient conditions provided 4-hydroxycoumrins in 85–90% yield. In medicinal chemistry, the 4-hydroxycoumarin motif is often used to make new hybrid heterocyclic scaffolds that can be used to find new molecules. The method was then successfully extended to synthesize hybrids of 4-hydroxycoumarin, such as biscoumarylphenylmethane, dioxinocoumarin, and tetracoumarylpehylenebismethane, in a one-pot method from phenol, avoiding the intermediate step of isolating and purifying 4-hydroxycoumarin.

Graphical Abstract

Keywords:

• 4-hydroxycoumarin
• biscoumarylphenylme­-thane
• dioxino-coumarin
• malonic acid
• one pot
• P₄O₁₀/TfOH
• phenol
• tetracoumaryl-phenylenebismethane

Acknowledgment

The authors thank the Syngenta Bioscience Pvt. Ltd., Goa for HRMS analysis. SGT to University Grant Commission, New Delhi for the award of BSR faculty fellowship (F.No.26–13/2020). GDK acknowledge to Goa University for the research studentship.

Disclosure statement

There are no conflicts to declare.