ZnOCl2 Catalyzed Synthesis and Characterization of Pyrano[2,3-c]-pyrazole Derivatives as Potent Antibacterial Agents

Title:ZnOCl2 Catalyzed Synthesis and Characterization of Pyrano[2,3-c]-pyrazole Derivatives as Potent Antibacterial Agents

Volume: 12 Issue: 4

Author(s): Manoj N. Bhoi, Mayuri A. Borad, Sanjay K. Rathwa, Edwin A. Pithawala and Hitesh D. Patel

Affiliation:

Keywords: Antibacterial activity, multi-component reactions, pyran, pyrano[2, 3-c]pyrazole, ZnOCl2.

Abstract: Background: Searching for well-organized organic synthesis approach that can be authenticated for the rapid generation of complex organic molecules from simple and readily accessible starting materials are in a vogue in the recent epochs. Recently, the developments of green protocols which are environmentally benign and without pollution have received substantial levels of consideration, owing to the increasing tendency of the chemical industry towards green synthetic methods. Multi-component reactions (MCRs) are one of the powerful tools. MCRs is influenced by microwave under solvent free condition as a powerful green alternative to the conventional synthesis. 4H-Pyrans derivative is essential building block in organic synthesis as well as in medicinal chemistry. Our aim is to find out the best environmental friendly catalytic system for the synthesis of pyranopyrazoles and carrying out organic reactions under solvent free condition

Synthesis of new and desired compounds have an endless demand. The present work shows one-pot, four-component, an efficient and solvent free synthesis of pyrano[2,3-c]pyrazole derivatives which have been accomplished by the cyclization reaction with excellent yields, using ZnOCl2 as a prompt catalyst. All the derivatives have been characterized by elemental analysis and various spectroscopic methods. All the final scaffolds have been subjected to in vitro antibacterial screening.

Methods: A mixture of aldehyde derivatives (1a-1g) 0.50 g (4.7116 mmol), malononitrile 2 0.31 g (0.299 g/ml) (4.1116 mmol), ethyl acetoacetate 3 0.61 g (4.7116 mmol) and 2, 4-dinitrophenyl hydrazine 4 (4.7116 mmol) were placed into 25 ml flat-bottomed flask in the presence of the catalyst, ZnOCl2 (10 mol %). The reaction mixture was heated at 60°C for 15- 45 min. The progress of the reaction was monitored by TLC. After consumption of starting materials, the mixture was poured into cold water and then extracted with ethyl acetate. The organic layer was dried over Na2SO4, and evaporated under reduced pressure. The aqueous layer was filtered to reuse and washed with methanol for two to three times to remove the strains. The isolated compounds (5a-5g) were then dried and subjected to column chromatography using 20% (v/v) Ethyl acetate: hexane mixture as an eluent with 90-96% yield of product. The catalyst was reused up to three cycles with a slight decrease of catalytic activity.

Results: First we performed four-component cyclization reaction between aldehyde derivative, malononitrile, ethyl acetoacetate and 2, 4-dinitrophenyl hydrazine as a model reaction to attaining the optimal reaction conditions. Results showed that the reaction proceeds in the presence of ZnOCl2 was better with yield and time as compared to all catalysts of the series. After getting optimal condition, we synthesized 5a-5g compounds by using ZnOCl2 as a catalyst. Antibacterial activity of synthesized compound was carried out on Nutrient-agar plates by well–diffusion assay against test culture. Compounds 5f, 5d, and 5b showed good activity to standard drug against Enterobacter aerogens, Escherichia coli, Bacillus cereus and Micrococcus luteus Gram positive bacteria, respectively.

Conclusion: In summary, we have developed an efficient method for the one-pot synthesis of various pyrano[2,3-c]- pyrazole derivatives by using ZnOCl2 as prompt catalyst. This protocol is very simple from the experimental point of view. We used a green and recyclable catalyst, high yield of products with high purity, avoiding the use of hazardous organic solvents, novelty and the simple work up, and there was not any requirement of anhydrous conditions, thus making the present method a valuable contribution in accord with green chemistry principles. The antibacterial and antioxidant activities of the synthesized compounds, were evaluated in vitro. The antibacterial data revealed that the all synthesized compounds proved to be active against the test organism, two gram negative and two gram positive reference strains as compared to standard drugs.

Cite this article as:

Bhoi N. Manoj, Borad A. Mayuri, Rathwa K. Sanjay, Pithawala A. Edwin and Patel D. Hitesh, ZnOCl2 Catalyzed Synthesis and Characterization of Pyrano[2,3-c]-pyrazole Derivatives as Potent Antibacterial Agents, Current Bioactive Compounds 2016; 12 (4) . https://dx.doi.org/10.2174/1573407212999160531114722