Design, synthesis and antibacterial evaluation of pyrano[3,2-H]quinoline carbonitriles

Abstract

Aim: To synthesize novel pyrano quinolines by one-pot multicomponent reaction under noncatalytic conditions, further it was proposed to investigate the reactivity of pyrano quinolines with the oxidizing agent like iodobenzene diacetate (IBD). Synthesized compounds were evaluated for antibacterial activity. Materials and Methods: Synthetic procedure: A mixture of aldehyde (1 mmol), malononitrile (1 mmol) in 10 ml of ethanol-water (1:1) was stirred for 10 min and then followed by addition of 8-hydroxy quinoline (1 mmol) and refluxed at 100°C for 1-2 h. The precipitated solid was collected by filtration. In the next step, to a suspension of pyrano[3,2-h]quinoline carbonitrile (1 mmol) in 5 mL of alcohol was added IBD (1.1 mmol) with stirring at room temperature open to air. The reaction mixture immediately became a clear solution followed by the precipitation of the product. The mixture was filtered and washed with the corresponding alcohol to afford the desired product. Antibacterial activity: All the synthesized compounds were screened for antimicrobial activity at a concentration of 100 μg/50 μl using ciprofloxacin as a standard drug. The minimum inhibitory concentrations (MICs) of these compounds were determined using broth microdilution MIC method. Results and Discussion: Synthetic studies: At the outset, pyrano[3,2-h]quinoline carbonitrile analogs 1(a-j) were constructed by a catalyst-free protocol via a one-pot, three-component condensation. Further, catalytic oxidative difunctionalization of the chromene double bond was achieved using hypervalent iodine reagents such as IBD in alcoholic medium and total 14 novel compounds 2(a-k) have been synthesized and confirmed on the basis of spectral data (infrared, nuclear magnetic resonance, and mass). Antibacterial activity: Among all the tested compounds, 1g, 1h, 1j, 2d, 2f, 2h, and 2k showed antibacterial activity against both Gram-positive and Gram-negative standard strains, and their MICs ranged between 1.56 and 12.55 μg/mL. Conclusion: In summary, an efficient, economical and eco-friendly multicomponent protocol for the construction of pyrano[3,2-h]quinoline carbonitriles has been achieved, and an oxidative difunctionalization of chromene double bond has been studied in the alcoholic solvent medium in the presence of IBD.