Synthesis, Characterization, and Antimicrobial Evaluation of Novel Thiohydrazonates and Pyrazolo[3,4-b]pyridines

Abstract

1,3-Diphenyl-1H-pyrazole-4-carbaldehyde and cyanothioacetamide were used to prepare the 2-thioxo-1,2-dihydropyridine-3-carbonitrile derivative, in a good yield, and taken as synthetic precursor for the present study. Pyridine-2(1H)-thione derivative reacted with hydrazonoyl halides in ethanol containing a few drops of triethylamine as a catalyst to afford the corresponding pyridin-2-yl-2-oxo-N-phenylpropanehydrazonothioate derivatives in excellent yields. Moreover, the reaction of Pyridine-2(1H)-thione derivative with α–chloroacetylacetone in ethanolic sodium acetate solution gave the corresponding 2-S-alkylpyridine derivative. The Japp–Klingemann reaction of the above 2-S-alkylpyridine derivative with the appropriate aryldiazonium chloride in pyridine afforded the same thiohydrazonates. Boiling of thiohydrazonates in ethanolic sodium ethoxide solution at reflux afforded the corresponding pyrazolo[3,4-b]pyridin-3-amines via consecutive rearrangement and cyclization. The in-vitro antimicrobial activities of the newly compounds were recorded. Thiohydrazonate 7d showed the highest inhibitory activity against all bacterial strains with minimum inhibitory concentration values of 3.9, 7.8, 7.8, and 15.6, μg/mL, respectively, against Klebsiella pneumonia, Staphylococcus aureus, Escherichia coli, and Streptococcus mutans, as compared to standard drugs for gram-positive and negative bacterial strains. The structure of the target molecules are elucidated using elemental analyses as well as spectral data.