Background: In these study we report here one-pot multi-component and solvent free Mannich
reaction of U.V. absorbing material, five member heterocyclic ring system and amides/carbamates has
been efficiently catalyzed by recyclable ethyl ammonium nitrate as ionic liquid at ambient temperature to
produce mannich compounds in high yields. This method has advantages of mild condition, no environmental
pollution, and simple work-up procedures to produce new mannich products 4(a-f). The synthesis
of five member based heterocycles has been the point of attraction towards their pronounced biological
activities and molecular docking studies.
Methods: The present methodology deals with one pot three component MCR’S reaction of five member
based 5-bromothiophene-2-carboxaldehyde, 2-hydroxy-4-methoxybenzophenone and various amides to
synthesize new mannich products 4(a-f) in refluxing with ethyl ammonium nitrate as ionic liquid at ambient
temperature within 4 to 5 hrs. The docking study was carried out with having receptor in Homo sapiens for
antibacterial, Pseudomonas spp. LL2 for anti-fungal and Mycobacterium tuberculosis H37Rv for anti-TB.
Results: A series of new synthesized mannich products shows in good to excellent yield (80-86%) via one
pot three component reactions. After separation of ionic liquid, obtained products were isolated in good yield
by the extraction of products thrice time in ethyl acetate. All of the isolated reaction products were characterised
and confirmed through, 1
C-NMR, Mass spectra and elemental analyses. In obtained products,
mainly 4b and 4c compound shows excellent property rather than 4e and 4f and provided desired products
in excellent yields may be due to the presence of electron withdrawing groups in five member heterocyclic
moiety. Some of the compounds showed in good agreement with its computationally predicted binding
energy (MolDock score) with high score in comparison with the rest of the molecules.
Conclusion: We have developed a green synthesis, good-yielding and mild reaction protocol for multi component
reactions to synthesize new mannich products via one pot three component reaction in solvent free
condition at 80ºC. It provided several advantages such as mild conditions and shorter reaction time, simple
and eco-friendly operational procedure. A significant activity was observed by the 4c and 4d compounds
against four bacterial and fungal strains while compounds 4a, 4e and 4f possess poor activity.
The anti-tuberculosis activity of four compounds shows poor activity as compare to the standard drug.