DABCO CATALYZED SYNTHESIS OF 4-SUBSTITUTED 2-AMINO9-CHLORO-3,4-DIHYDRO-4H-PYRANO[3,2-c]QUINOLINE-3CARBONITRILES: THEIR CHARACTERIZATION AND ANTIMICROBIAL ACTIVITIES

Abstract

A simple and efficient one-pot synthesis of fused 4-substituted 2-amino-9-chloro-3,4dihydro-4H-pyrano[3,2-c]quinoline-3-carbonitriles (Z-1-1 to Z-1-7) has been developed via initial Knoevenagel, subsequent Michael and final heterocyclization reactions of heteroaryl aldehyde, malononitrile and 7-chloro-4-hydroxyquinoline. 1,4-Diazabicyclo [2.2.2] octane (DABCO) has been used as a catalyst. Environment friendly procedure and very good yields (83-92%) are the main advantages of this procedure, although has taken long reaction time (7-12h). Structures of the synthesized compounds were elucidated by using different spectroscopic techniques such as, 1H NMR, 13C NMR, and HRMS. Melting point of all the synthesized compounds was determined by electrothermal melting point instrument. All the products were assayed in vitro for their antimicrobial activities against two bacterial species, one gram-positive (Staphylococcus aureus) and one gram-negative (Escherichia coli). Similarly two fungal species (Aspargillus niger and Fusarium moniliformale) were tests using paper disc diffusion method. In addition to this all the synthesized compounds were evaluated for their antitubercular activities against M.tuberculosis H37Rv by agar microdilution method. The mean zone inhibitions of Chloramphenicol (antibacterial) and tilt (antifungal) Rifampicin, Ethambutol, Isoniazid (antitubercular) were used as a positive control. The antibacterial and antifungal activities tests indicate that Z-1-4 has a good potency for both bacterial species (Escherichia coli and Staphylococcus aureus) in both doses 10 and 20 (15.2 0.8 mm and 32 2.0 mm) and (18.8 0.8 mm and 37 1.3 mm), respectively. On the other hand, Z-1-7 have a good potency for both fungal species (Aspargillus niger and Fusarium moniliformale) in both doses, 10 and 20 , (19.8 0.4 mm and 38 0.4 mm) and (16.8 0.4 mm and 34 0.4 mm), respectively. The antitubercular activities tests indicated that from all the synthesized compounds six of them showed moderate to very good except Z-1-1. Z-1-5, Z1-6, Z-1-7 have a very good antitubercular activities compared to reference drug MIC=1.56 g mL