Solvent Free Green Protocol for the Synthesis of Anti-Bacterial Schiff Base Dimers

Abstract

A novel series of Schiff base dimers have been designed and synthesized from phthalaldehydes and various amines including aliphatic, aromatic and heterocycles by grinding at room temperature. This solvent free green protocol approach is superior to the classical approach which uses ethanol as solvent. The advantage of this new method is that wide substrates can be incorporated, very simple to carry out the reaction, easy workup with high product yield. Compounds obtained have been screened for anti-bacterial activity against nine different strains (six Gram-negative and three Gram-positive) which include E.coli, Proteus mirabilis, Klebsiella pneumonia, Proteus vulgaris, Morganella morgana, Salmonella typhi, Staphylococcus aureus, Methicillin-resistant Staphylococcus aureus, Enterococci faecalis. Among them, the heterocyclic groups in the side chain of the Schiff base showed better activity than the aromatic and aliphatic groups. Particularly the thiophene substituted 1,4-isomer of the Schiff base dimer showed good antibacterial activity against seven strains. Interestingly, the 1,3 isomer of the Schiff base dimer with thiophene substituent exhibited a potent antibacterial activity. An effective Structure-Activity Relationship have also been established for the Schiff base dimers to find novel and potent anti-bacterial agents.