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Synthesis, Characterizations and Microbial Studies of Novel Mannich Products Using Multicomponent Reactions

[ Vol. 14 , Issue. 3 ]

Author(s):

Hitendra M. Patel*   Pages 278 - 288 ( 11 )

Abstract:


Background: We developed Multicomponent synthesis for novel Mannich products with biologically active quinoline nucleolus under solvent free condition. This methodology provided us good amount of yield with the exception of chromatographic separation. The structure of novel compounds (4d1-d13) was characterized by elemental, mass, 1H-NMR, 13C-NMR and IR spectroscopic analysis. In vitro antimicrobial studies also indicate that most of the compounds are active against gram positive and gram negative bacteria. M. Tuberculosis activity of five compounds shows excellent properties.

Methods: The present methodology deals with Multicomponent reaction, in which, the mixture of 2,4- dihydroxybenzophenone 1.07 gm (0.005 M), 2-chloro-6-methoxyquinoline-3-carboxaldehyde 1.105 gm (0.005 M), with various amines 0.30 gm (0.005M) and EAN 30 ml (1 M) was stirred at 80°C temperature. The completion of reaction was monitored by TLC by using (chloroform/methanol, 70:30). On completion of the reaction, the reaction mixture was extracted thrice with 20 ml ethyl acetate. The extract was dried over anhydrous sodium sulfate, evaporated under vacuum and the residue was purified via recrystallisation from methanol or ethyl acetate to obtain pure new Mannich products 4(d1-d13). All synthesized compounds were screened for their in vitro antibacterial activity by using the agar dilution technique.

Results: The promising results obtained using 1M EAN as catalyst at the 80°C temperature encouraged us to investigate the feasibility of solvent-free MCRs protocol for the synthesis of new Mannich products 4(d1-d13). The recovery and recyclability of EAN were investigated for the synthesis of new Mannich products 4(d1-d13). It was found that, recycled ionic liquid was used up to four to five times without the loss of catalytic activity. The high yield (90-95%) of this products was observed at milder reaction condition compared to the other ionic liquid which rationalized due to high acidity associated with it (pH=5) along with its capacity to absorb water formed during the course of the reaction. All the compounds showed very good activity accept 4d13, especially against P. aeruginosa MTCC 1688 (MIC=25- 75 µg/mL), E. coli MTCC 443 (MIC = 25-100 µg/mL) and S. aureus MTCC 96 (MIC=25–75 µg/mL) whereas, 4d3 and 4d12, were found to be more potent rather than standard drugs Chloramphenicol and Ciprofloxacin. All the compounds showed excellent antifungal activity against C. albicans MTCC 227 (MIC=75-100 µg/mL) and A. niger MTCC 282 (MIC=75-100 µg/mL) whereas, 4d2 to 4d7 were found more potent rather Nystatin and Griseofulvin. Antituberculosis activity of all the compounds showed excellent activity 0.10 µg/mL rather than standard drug isoniazide (0.20 µg/mL) accept 4d2 and 4d3 using L. J. medium conventional method.

Conclusion: We developed an environmental friendly, high yield and mild condition protocol for the three-component Mannich-type reactions using EAN as ionic liquid. This method provided us several advantages by comparison with reported literature; which are as follows: (a) highly efficient catalyst activity, (b) ease of workable with green catalyst, (c) reaction proceeds without preparation of enol derivatives and pre-formed imines, (d) effective reusability of catalyst, making it a useful and attractive strategy. EAN was recovered and recycled four to five times without decreasing catalytic activity. Most of the compounds showed potential activities against Gram-positive bacteria rather than Chloramphenicol and Ciprofloxacin, accept 4d13. Compounds 4d3 to 4d12 were found to be more potent against C. Albicans and A. Niger rather than Nystatin and Griseofulvin. Antituberculosis activity of 4d8 to 4d12 compounds showed excellent activity rather than isoniazide against H37RV bacteria using L. J. medium conventional method.

Keywords:

Solvent-free, multicomponent reactions, heterocyclic compounds, reusable ionic liquid, 2, 4- dihydroxybenzophenone, Mannich products, quinoline moity.

Affiliation:

Department of Chemistry, Sardar Patel University, Vallabh Vidyanagar 388120

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