Synthesis, antibacterial and antifungal activity of some new pyrazoline and pyrazole derivatives

Abstract

A series of 2-pyrazolines 5-9 have been synthesized from α,β-unsaturated ketones 2-4. New 2-pyrazoline derivatives 13-15 bearing benzenesulfonamide moieties were then synthesized by condensing the appropriate chalcones 2-4 with 4-hydrazinyl benzenesulfonamide hydrochloride. Ethyl [1,2,4] triazolo[3,4-c][1,2,4]triazino[5,6-b]-5H-indole-5-ethanoate (26) and 1-(5H-[1,2,4]triazino[5,6-b] indol-3-yl)-3-methyl-1H-pyrazol-5(4H)-one (32) were synthesized from 3-hydrazinyl-5H-[1,2,4]triazino[5,6-b]indole (24). On the other hand ethyl[1,2,4]triazolo[3,4-c][1,2,4]triazino[5,6-b]-5,10-dihydroquinoxaline- 5-ethanoate (27) and 1-(5,10-dihydro-[1,2,4]triazino[5,6-b]quinoxalin-3-yl)-3-methyl-1H-pyrazol-5(4H)-one (33) were synthesized from 3-hydrazinyl-5,10-dihydro-[1,2,4]triazino[5,6-b]quinoxaline (25) by reaction with diethyl malonate or ethyl acetoacetate, respectively. Condensation of 6,6-dimethyl-4-oxo-4,5,6,7-tetrahydro-1H-indole-2-carbaldehyde (1') with compound 24 or 25 afforded the corresponding Schiff's bases 36 and 37, respectively. Reaction of the Schiff's base 37 with benzoyl hydrazine or acetic anhydride afforded benzohydrazide derivative 39 and the cyclized compound 40, respectively. Furthermore, the pyrazole derivatives 42-44 were synthesized by cyclization of hydrazine derivative 25 with the prepared chalcones 2-4. All the newly synthesized compounds have been characterized on the basis of IR and 1H-NMR spectral data as well as physical data. Antimicrobial activity against the organisms E. coli ATCC8739 and P. aeruginosa ATCC 9027 as examples of Gram-negative bacteria, S. aureus ATCC 6583P as an example of Gram-positive bacteria and C. albicans ATCC 2091 as an example of a yeast-like fungus have been studied using the Nutrient Agar (NA) and Sabouraud Dextrose Agar (SDA) diffusion methods. The best performance was found for the compounds 16, 17, 19 and 20.

Scheme 1

Synthesis of chalcones 2–4, pyrazoline derivatives 5–9 and isoxazoline derivatives 10–12.

Scheme 2

Synthesis of benzenesulfonamide derivatives 13–21.

Scheme 3

Synthesis of [1,2,4]triazolo[3,4-c][1,2,4]triazino[5,6-b]-5-N-(phenylcarbamothioyl) ethanoic acid hydrazide derivatives 30, 31 and 3-methyl-4-(propan-2-ylidene)-1H-pyrazol-5(4H)-one derivatives 34, 35.

Scheme 4

Synthesis of Schiff’s bases 36, 37, 4-oxo-4,5,6,7-tetrahydro-1H-indol-2-yl)thiazolidin-4-one (38), benzohydrazide derivative 39, 1,2,4]triazolo[3,4-c]-5,10-dihydro [1,2,4]triazino[5,6-b] quinoxaline (40), and pyrazole derivatives 41–44.

Scheme 5

Charge distribution on nitrogen atoms N₁, N₃ of compound 37.