Studies on The Synthesis of Fluorinated Schiff Bases; Biological Activity of Resulting (E)-N-Benzylidene-2,3,5,6-Tetrafluoropyridin-4-Amine and 4-Amino-2-Ethoxy-3,5,6-Trifluoropyridine

Abstract

The present work is aimed mainly to synthesize new fluorinated compounds and their biological significance against tested bacteria and fungus. Thus, the 4-amino-2-ethoxy-3,5,6-trifluoropyridine 4 was synthesized by the reaction of 4-amino 2,3,5,6-tetrafluoropyridine 1 with benzaldehyde 2 in EtOH to obtain the pure product as white crystals in 33% yield. The purity of this compound was estimated by TLC technique and microanalysis while its structure was supported by the usual spectroscopic methods such as UV, infrared, 1 H. NMR, and gas chromatography coupled by a mass spectrometry (GC/MS). 4-amino 2,3,5,6-tetrafluoropyridine 1 coupled readily to benzaldehyde 2 when we have used THF as solvent resulting a new Schiff base (E)-N-benzylidene-2,3,5,6-tetrafluoropyridin-4-amine 3 in 48 % yield. Exploration of the anti-bacterial activity against both gram-positive and gram-negative bacteria showed that these compounds 3 and 4 compounds at a concentration of 250 µg/ml exhibited a slight activity towards Enterococcus feacium; Streptocoque B and Staphylococus aureus exhibited a mild/moderate activity for the case of Escherichia coli and Salmonella typhimurium when compared to Ampicillin. From the results obtained by the antifungal activity, it is found that this fluorinated Schiff base 3 and fluorinated ethoxypyridine 4 are more active against Candida albicans at a concentration of 250 µg/ml when compared to Nystatine.

An Insight into Fluorinated Imines and Hydrazones as Antibacterial Agents

“…Raache et al [ 15 ] have reported the synthesis, structural investigations and preliminary antibacterial activity studies of ( E )-1-phenyl- N -(2,3,5,6-tetrafluoropyridin-4-yl)methanimine ( 1 ) ( Figure 1 ). The synthesis of this aldimine was achieved successfully by reacting equimolar ratios of 4-amino-2,3,5,6-tetrafluoropyridine and benzaldehyde in tetrahydrofuran containing an ethanolic solution of potassium hydroxide for 72 h at ambient temperature.…”

“…Ampicillin—a broad-spectrum aminopenicillin—was used as a standard antibiotic. Tetrafluorinated aldimine 1 at the highest concentration tested (983.5 µM) was shown to reveal moderate activity against both Gram-negative bacteria of clinical interest, considering its zone inhibition sizes in relation to that of ampicillin [ 15 ].…”

“…Ampicillin-a broad-spectrum aminopenicillin-was used as a standard antibiotic. Tetrafluorinated aldimine 1 at the highest concentration tested (983.5 µM) was shown to reveal moderate activity against both Gram-negative bacteria of clinical interest, considering its zone inhibition sizes in relation to that of ampicillin [15]. Avila-Sorrosa et al [16] have described a straightforward synthesis route, determination of the structure (including that in the solid state) and preliminary antibacterial evaluation of fluorinated aldimine-type Schiff bases 2-4 (Figure 2).…”