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

• Published in: Synthetic communications Vol. 54; no. 5; pp. 379 - 389
• Main Authors: Kotkar, G. D., Tilve, S. G.
• Format: Journal Article
• Language: English
• Published: Philadelphia Taylor & Francis 03.03.2024; Taylor & Francis Ltd
• Subjects: 4-hydroxycoumarin; Biological effects; biscoumarylphenylme­-thane; Chemical synthesis; dioxino-coumarin; malonic acid; one pot; phenol; Phenols; Phosphorus pentoxide; Reagents; Scaffolds; tetracoumaryl-phenylenebismethane; TfOH
• ISSN: 0039-7911; 1532-2432
• DOI: 10.1080/00397911.2024.2306610

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 (P 4 O 10 /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.