SYNTHESIS OF PARACETAMOL DERIVATIVES AS MANNICH BASES AND THEIR ANTIBACTERIAL ACTIVITY

Abstract

Aim: A variety of Paracetamol derivatives as mannich bases were prepared through mannich reaction by reacting Paracetamol as compound containing active hydrogen, substituted benzaldehyde, morpholine as secondary amine compound and small amount of conc. HCl as catalyst. A simplistic one-pot method under mild conditions has been developed for the synthesis of all the compounds and they were characterized by physically (Rf values, Melting point, Molecular weight, Molecular formula) and by spectral data (IR and 1H-NMR spectral analysis). Antibacterial activity was carried out by using cup plate method. All the newly synthesized compounds were screened for antibacterial activity against gram positive and gram negative microorganisms i.e. Staphylococcus aureus, Bacillus subtilis, Escherichia coli, Pseudomonas aeruginosa in comparison with standard drug Streptomycin. Methodology: The 1H-NMR spectra chemical shifts in ppm were recorded on Bruker NMR 400 MHZ using spectrophotometer using DMSO-d6 as solvent. The IR spectra of the synthesized compounds were recorded on Bruker FT-IR spectrophotometer with KBr pellets. The progress of the reaction and purity of the compounds was checked by TLC on pre-coated silica gel G plates by using n-hexane:ethyl acetate (9:1) v/v as a mobile phase and visualized in UV cabinet. Conclusion: A facile one-pot method under mild conditions has been developed for the synthesis of the title compounds. All the compounds were evaluated for their antibacterial activity against gram +ve and gram -ve micro-organisms by cup plate method. 3-(4-chlorophenyl)-3-(morpholine-4-yl)-N-(4-hydroxyphenyl)-propanamide 4a gives high % yield. The antibacterial screening results states that compound 4b shown significant activity against S. aureus, 4a and 4b compounds shown significant activity against B. subtilis, compound 4b shown significant activity against E. coli and compound 4f shown significant activity against P. aeruginosa.

Keywords

• Paracetamol
• Substituted benzaldehydes
• Morpholine
• Mannich reaction
• In vitro antibacterial activity