Synthesis of 4-Hydroxycoumarin and its Derivatives

Author

MUHAMMAD HAFFIZ JAURI*, FAREDIAH AHMAD, & HASNAH MOHD SIRAT

Proceeding

The 21st Annual Seminar of the Malaysian Natural Product Society.(Herbal Medicine:Natural Products S ciety), Palm Garden, Putrajaya Malaysia.

Date

22/11/2005

Keyword

Claisen Condensation, 4-hydroxycoumarin, 4-methoxycoumarin, 4-acetylcoumarin, N-[2-(2-oxo-2H-chromen-4-yl amino)-ethyl]acetamide, 3-(1,1-dimetyl-3-oxobutyl)-4-hydroxycumarin

Abstract

4-Hydroxycoumarin is a lactone that can be synthesized by Claisen condensation. The synthesis of 4-hydroxycoumarin involved the condensation of o-hydroxy acetophenone and diethyl carbonate with NaH as a base. The methylation of 4-hydroxycoumarin with methyl iodide in the presence of potassium carbonate afforded 4-methoxycoumarin while acetylation of 4-hydroxycoumarin with acetic anhydride in the presence of dry pyridine yielded 4-acetylcoumarin. The reaction of 4-hydroxycoumarin with ethylene diamine in acetic acid afforded N-[2-(2-oxo-2H-chromen-4-ylamino)-ethyl]acetamide while with mesityl oxide in the presence of pyridine yielded 3-(1,1-dimethyl-3-oxobutyl)-4-hydroxycoumarin. All the compounds were characterized by spectroscopic techniques, i.e IR, MS and NMR (1H and 13C). The toxicity test with Artemia salina was carried out on 4-hydroxycoumarin, 4-acetylcoumarin and 4-methoxycoumarin. 4-Hydroxycoumarin and 4-acetylcoumarin were not toxic while 4-methoxycoumarin was found toxic againt Artemia salina with ED50 187.7 ppm.