Synthesis and Antimicrobial Activity of Some Novel Pyrazolones

Pyrazolone containing compounds are associated with antimicrobial1, antiviral2, antifungal3, antioxidant4, cytotoxic5, analgesic6, anti-inflammatory7activities.Thiophene derivatives have found very important place in the field of drug discovery because of their potential biological activities8. Thiazoles have found applications in drug development for treatment of HIV infections9, hypertension10 and as inhibitors of bacterial gyrase B11. Moreover pyrazole containing compounds are reported to have good biological activities like antimicrobial12, antifungal13, antiviral14,analgessic15,anti parastic16 and antineoplastic17.


INTRODUCTION
Multi drug resistant micro-organisms and increased systemic as well as infectious diseases are the two major challenges for scientific world.Development of newer synthetic entities can offer a major solution for these problems.
Pyrazolone containing compounds are associated with antimicrobial 1 , antiviral 2 , antifungal 3 , antioxidant 4 , cytotoxic 5 , analgesic 6 , anti-inflammatory 7 activities.Thiophene derivatives have found very important place in the field of drug discovery because of their potential biological activities 8 .
Thiazoles have found applications in drug development for treatment of HIV infections 9 , hypertension 10 and as inhibitors of bacterial gyrase B 11 .Moreover pyrazole containing compounds are reported to have good biological activities like antimicrobial 12 , antifungal 13 , antiviral 14 ,analgessic 15 ,anti parastic 16 and antineoplastic 17 .
Pyridine nucleus is important nitrogen heterocycle which exhibits antimicrobial 18 , a n t i c a n c e r 19 a n d a n t i ox i d a n t 20 a c t i v i t i e s.Imidazole derivatives have been shown to exhibit antibacterial 21 , antifungal and antioxidant 22 activity.
It has been shown that substitution pattern of bromine can alter the activity of a compound 23 .Fluorine containing compounds are associated with bioactivities such as antibacterial 24 , anticancer 25 and analgesic 26 .
Knoevenagel condensation 27 reaction shave occupied an important place in synthetic organic chemistry due to its efficiency in carboncarbon bond formation.Many researchers have studied Knoevenagel condensation reactions of various aldehydes with pyrazolones [28][29] .
Activities associated with pyrazolones, thiophenes, pyrazoles, imidazoles and halogens prompted us to synthesize compound containing these moieties.

EXPERIMENTAL
Physical constants were determined in open capillary.IR of the compounds were recorded using IR Affinity-1 Fourier transform infrared spectrophotometer (Shimadzu).PMR spectra were taken using Bruker Avance II 400 MHz NMR spectrometer.TMS was used as an internal standard and DMSO-d 6 as a solvent.The mass spectra were recorded on HP 1100 LC/MS.The mixture of 3-(5-bromothiophen-2-yl)-1-(2,3-dimethylphenyl)-1H-pyrazole-4-carbaldehyde A (0.01 mol) and 2-(2,3-dimethylphenyl)-5-propyl-2,4-dihydro-3H-pyrazol-3-one B (0.01mol) in 5 mL of glacial acetic acid was refluxed in round bottom flask for 30 min.Reaction progress was studied and confirmed using TLC at the end of reaction, reaction mixture was poured over ice.Product obtained 1 was separated using simple filtration then purified by re crystallization from ethanol.Compounds 2,3 and 4 were synthesized using same procedure.Physical data of all the synthesized compounds is given in Table 1 and spectral data as below.

RESULTS AND DISCUSSION
Pyrazolone derivatives were condensed with various aldehydes to obtain the products 1, 2, 3 and 4. Compound 1a in its IR spectrum shows carbonyl frequency band at 1676 cm -1 of pyrazolone ring.PMR spectrum of the compound exhibited signals of propyl side chain, a triplet at d1.04 due to methyl group, sextet for methylene at d1.77 and triplet at d 2.68 for another methylene.Compound 2g, in its IR spectrum exhibited band at 1651cm -1 for C=O group.PMR spectrum showed singlet at d 7.45 for 1H due to olefinic proton and a doublet at d 8.18 for 1H with J = 5.6 Hz for pyridine ring proton.Compound 3d, exhibited a band due to carbonyl group at 1681 cm -1 .PMR spectrum of 3d showed the signals at d 1.01 triplet for 3H with J =7. 4

Antimicrobial activity
The antimicrobial activity of synthesized compounds 1a-h, 2a-g, 3a-e and 4a-e was determined in vitro against three bacterial strains Bacillus subtilis, Escherichia coli, Salmonella typhi and two fungal strains Alternaria alternata and F. Oxisporum.The antimicrobial activity of compounds against test fungi and bacteria by using well diffusion technique.Ciprofloxacin was used as reference compound for bacteria and ketoconazole for fungi.All the experiments were performed in triplicate.
From seen activities for tested microorganisms are not observed for our compounds.
Scheme -1 Hz, d1.75 sextet for 2H with J = 7.4 Hz and d 2.66 triplet for 2H with J = 7.4 Hz corresponding to propyl group.Signals at d 7.57, dd, 1H, J =1.0 & 3.6 Hz, d 7.72 dd, 1H, J = 1.0 & 5.1 Hz are due to thiophene ring.Olefinic proton is observed at d 7.78 as a singlet.Singlet at d 9.74 is due to proton on pyrazole ring.Compound 4a, showed band due to carbonyl group at 1687cm -1 .PMR spectrum of the compound exhibited three singlets at d 2.09, 2.35 and 2.45 due to three methyl groups.Singlets at d 7.82 and 10.23 are due to olefinic proton and pyrazole ring proton respectively.