Synthesis, Structural Elucidation, and Antibacterial Evaluation of Some New Molecules Derived from Coumarin, 1,3,4-Oxadiazole, and Acetamide

Shahid Rasool,Aziz-Ur-Rehman Aziz-Ur-Rehman,Irshad Ahmad,Muhammad Athar Abbasi,Syed Adnan Ali Shah,Sabahat Zahra Siddiqui,Sidra Hassan

doi:10.1155/2016/8696817

Abstract

Because of the reported biological activities of coumarin, 1,3,4-oxadiazole, and acetamides, some new compounds incorporating these moieties were synthesized and evaluated for their biological potential against Gram-positive and Gram-negative bacteria. In the present work, 4-chlororesorcinol (1) and ethyl acetoacetate (2) were mixed in a strong acidic medium to synthesize 6-chloro-7-hydroxy-4-methyl-2-oxo-2H-chromene (3) which was subjected to the intermolecular cyclization after consecutive three steps to synthesize 5-[(6-chloro-4-methyl-2-oxo-2H-chromen-7-yl)oxy]methyl-1,3,4-oxadiazol-2-thiol (6). A series of acetamoyl electrophiles, 8a–o, were synthesized from aralkyl/alkyl/aryl amines, 7a–o, in an aqueous basic medium. The final compounds, 9a–o, were synthesized by the reaction of compounds 6 and 8a–o in DMF/NaH. The synthesized compounds were structurally elucidated by spectral data analysis of IR, 1H-NMR, and EIMS. The most of the synthesized compounds remained moderate to excellent antibacterial agents. The molecules, 9e, 9j, and 9k, were the most efficient ones against all the five bacterial strains taken into account.

Highlights

Coumarin is a naturally occurring heterocyclic class of compounds [1,2,3]
The different derivatives of various coumarins have been introduced synthetically and by plant extraction to possess a number of biological activities including antibacterial, antioxidant, and anti-inflammatory activities [6,7,8,9]
The different N-aralkyl/alkyl/aryl acetamides incorporating coumarin and 1,3,4-oxadiazole rings, 9a–o, were synthesized by the multistep protocol given in Scheme 1

Summary

Introduction

Coumarin is a naturally occurring heterocyclic class of compounds [1,2,3]. The different derivatives of various coumarins have been introduced synthetically and by plant extraction to possess a number of biological activities including antibacterial, antioxidant, and anti-inflammatory activities [6,7,8,9]. The heterocyclic moiety, 1,3,4-oxadiazole, and its various 2,5-disubstituted products are known to be biologically active compounds [10,11,12]. The presence of amide functionality is known to boost up the potential of bioactive compounds including antifungal, anti-inflammatory, anticancer, antibacterial, and antioxidant activities [13,14,15,16]. In continuation of our previous work on O-substituted derivatives [19] and notable bioactivity of ether derivatives of coumarin [6, 9, 20] this prompted us to incorporate coumarin with 1,3,4-oxadiazole and acetamides to evaluate their antibacterial activity

Experimental

Results and Discussion

Conclusion