Synthesis of phenyl esters 2-oxo-2H-1-benzopyran-3-carboxylic acids as promising antimicrobial agents

Abstract

Corresponding chloroanhydrides were synthesized by the interaction of coumarin-3-carboxylic and 6-methoxycoumarin-3-carboxylic acids with an excess of thionyl chloride under heating. Due to the quantitative yields and the formation of volatile products within the reaction, chloroanhydrides were used without additional purification in acylation of substituted phenols for the synthesis of phenyl esters of 2-oxo-2H-1-benzopyran-3-carboxylic acids. The reaction was carried out by heating in anhydrous dioxane environment in the presence of pyridine as a catalyst. The structure of the obtained esters was proven using instrumental methods of analysis. The antimicrobial and antifungal activity of the synthesized compounds was studied in vitro by the method of two-fold serial dilutions in liquid and solid nutrient environments. Antimicrobial activity screening showed that the synthesized esters have a moderate activity against gram-negative microorganisms and C. albicans. It was found that the 4-methyl-2-chlorophenyl ester of coumarin-3-carboxylic acid had the greatest bacteriostatic activity against Ps. aeruginosa and Pr. vulgaris, 2-chlorophenyl ester of coumarin-3-carboxylic acid against Ps. aeruginosa and E. coli, coumarin-3-carboxylic acid 4-hydroxyphenyl ester against Pr. vulgaris, and coumarin-3-carboxylic acid 2-isopropyl-5-methylphenyl ester against E. coli at a concentration of 31.25 g/ml. 2-Chlorophenyl ester also showed a bactericidal effect against E. coli. The synthesized compounds also have an antifungal effect against the C. albicans. strain used in the experiment. Thus, 4-methyl-2-chlorophenyl ester, 4-fluorophenyl ester, 4-hydroxyphenyl ester, 2,3-dihydroxyphenyl ester, 2-isopropyl-5-methylphenyl ester of coumarin-3-carboxylic acid are active at a concentration of 31.25 g/ml.