Synthesis and Antimicrobial Activity of Some [1,2,4]-Triazole Derivatives

A series of novel [1,2,4]-triazolo piperidine (8), [1,2,4]-triazolo piperazine (9a-c), [1,2,4]-triazolo phenylether (10a-e), and [1,2,4]triazolo aniline (11a-c) derivatives have been synthesized. e chemical structures of the newly synthesized compounds were characterized by IR, H NMR, C NMR, and LCMS. e newly synthesized compounds were screened for antimicrobial activity. Among all the compounds tested, 11b (R4 = 4-MeO–) showed the highest activity against Staphylococcus aureus and Escherichia coli, and 9a (R1 and R2 = Cl) showed the highest activity against Pseudomonas aeruginosa.


Introduction
e antimicrobial agents available now have various drawbacks such as toxicity, drug resistance to microbes, and narrow spectrum of activity.Hence the design of new compounds to deal with the above problems has become one of the most challenging targets in antibacterial and antifungal research today.
In view of all these facts, the aim of the present study is to synthesize 1,2,4-triazole-3-one containing piperidine, piperazine, phenylether, and aniline with the hope that new antimicrobial agents will be developed.

Experimental Section
Melting points were determined on a Buchi B-545 melting point apparatus and are uncorrected. 1H NMR spectra of the samples in CDCl 3 and DMSO- 6 were recorded on a Bruker Avance (300 or 400 MHz) spectrometer using tetramethylsilane (TMS) as an internal standard. 13C NMR spectra were recorded in DMSO- 6 at 100 MHz with TMS as an internal reference.IR spectra were recorded on a Nicolet 6700 FT-IR spectrometry using ATR-technique (ATR = Attenuated Total Re�ectance).C, H, N, and S analyses were carried out on an Elementor (Vario microcube).Mass spectra were recorded on a LC-MS-Agilent 1200 spectrometer.(8) and Piperazine (9a-c) Derivatives.To a solution of compound (7) (4 mmol) in DMF (8 mL) was added substituted piperidine/piperazines (4.4 mmol), Cs 2 CO 3 (6 mmol), and

General Procedure for the Synthesis of Phenol Derivatives (10a-e).
A mixture of compound (7) (4 mmol), the appropriate substituted phenols (4.4 mmol), Cs 2 CO 3 (6 mmol), and CuI (0.4 mmol) in DMF (8 mL) was stirred at 100 ∘ C for 13-15 h.Aer completion of the reaction, the mixture was poured on to ice water.e product was extracted with ethyl acetate (2 × 50 mL).e combined organic phases were washed with water (2 × 50 mL) and brine (50 mL).e organic phase was dried over sodium sulfate and the solvent was evaporated under reduced pressure to give phenylethers (10a-e) in good yields. 4

Compounds
Gram

Biology
3.1.Antimicrobial Activity.e in vitro antimicrobial activity was carried by using the disc diffusion method [33,34].All the newly synthesized compounds were evaluated for their antibacterial activity against Bacillus subtilis, Staphylococcus aureus, Staphylococcus epidermidis, Escherichia coli, and Pseudomonas aeruginosa.e antifungal activity was evaluated against R. oryzae, A. niger, A. �avus, C. albicans, and S. cerevisiae.e minimum inhibition concentration (MIC) was determined by using the twofold serial dilution method with 64-well microtest plates.e test compounds were dissolved in dimethylformamide (DMF).Further dilutions were made at the required concentrations of 300, 150, 75, 37.5, 18.75, 9.75, 6.25, 3.125, and 1.56 g/mL, respectively.Streptomycin and Penicillin were used as reference standards for antibacterial activity and Amphotericin-B as reference standard for antifungal activity.e standard drugs were selected based on our previous work [1] in order to compare the activity.e results of antibacterial and antifungal activity are given in Tables 1 and 2, respectively.

Results and Discussion
From the experimental results, we observed that the Cs 2 CO 3 works better for compounds (8), (9a-c), and (10a-c) while, for less reactive anilines organic base, triethyl amine works better compared to Cs 2 CO 3 .Hence, triethylamine is used as excellent base for these reactions which in turn increases safety and cost effectiveness.
e formation of compounds 10a-e and 11a-c from 7 was con�rmed by 1 H NMR spectrum.e methylene protons of 10a-e Ar-OCH 2 -and triazole-N-CH 2 -were observed in the ranges of 4.45-4.16and 4.16-4.00ppm, respectively.e signals in the range 7.84 to 6.74 ppm are due to the aromatic protons.In addition, the two distorted triplets appeared in the ranges 3.80-3.73and 3.35-3.25ppm are assigned to the methylene protons.e triplet for single proton of Ar-NHwas observed in the range 5.85-5.4ppm.e peaks in the range 6.78 to 6.50 ppm are assigned to the aromatic protons.e compounds 10a-e and 11a-c were further con�rmed by their stable M+1 ion peaks in mass spectra.
From the antibacterial activity results it was observed that compounds 11b (R 4 = 4-MeO-) showed the highest activity against Staphylococcus aureus and Escherichia coli.e compound (9a) (R 1 and R 2 = Cl) showed the highest activity against Pseudomonas aeruginosa.However, relatively lesser activity was noticed in compounds 9b and 9c due to the substitution of one or both chlorine atoms in 9a by �uorine.is difference in activity may be attributed to the presence of bulkier as well as more lipophilic chlorine atoms in 9a.Almost all the newly synthesized compounds have poor activity against all types of fungal strains tested.