Synthesis and Antibacterial Screening of Novel Thiazolyl Pyrazole and Benzoxazole

A new series of (2-hydroxyphenyl)(1-(4-p-tolylthiazol-2-yl)-1H-pyrazol-4-yl)methanone 3a-g, 2[(E)–{1-[4-(p-tolyl)-1, 3-thiazol-2-yl)]-1H-pyrazol-4-yl} (hydroxyimino)methyl]phenol 4a-g and 2-(1-(4-p-tolylthiazol-2-yl)-1H-pyrazole-4-yl)benzo[d]oxazole 5a-g have been synthesised. These synthesised compounds have been characterised by the spectral, analytical data and scanned for their antibacterial activities. keywords: Thiazole,3-formylchromone, Pyrazole, Benzo[d]oxazole.


INTROdUCTION
The introduction of heterocyclic moieties found in molecules have advantage in drug discovery and development because of its broad range of biological activities.Thiazole and its derivatives show biological activities such as anti-inflammatory 1 , analgesic 2 , antimicrobial 3,4 , antioxidant 5 , antitumor 6,7 , anticonvulsant 8 .3-formylchromone and its derivatives are known to associate in organic synthesis 9 and showing biological activities include antitumor 10 , antibacterial 10 , antitubulin 11 , anti-helicobacter pylori 12 , antiallergic 13 , antioxidant 14 , topoisomerase I inhibitor 15 .Pyrazole containing heterocyclic molecules are associated with wide range of biological activities such as antimicrobial 16 , anticancer 17 , antifungal 18 , anti-inflammatory 19 , antitumor 20 , and anti-anxiety 21 .Benzoxazoles derivatives are found to be associated with anticancer 22 , antimicrobial 23 , HIV-1 reverse transcriptase Inhibitor Activity 24 , inhibitors of lysophosphatidic acid acyltransferase-beta 25 , anti-inflammatory 26 , analgesic 26 , antibacterial 27 , antifungal 27 , anticancer 28 activities.As a part of our interest in heterocyclic molecules have a extensive variety of biological activities and that have been explored for developing pharmaceutically important molecules, we here in report the synthesis of a set of new series of thiazolyl pyrazoles and benzoxazoles and their antibacterial activities.

EXPERIMENTAL
All the chemicals were from Sigma -Aldrich and used without any purification.Melting Points of synthesised compounds were taken in open capillary tubes and uncorrected.IR spectra were obtained in KBr pallet on a FT-IR spectrophotometer and Mass spectra were recorded on a Q-TOF MS ES-3.84e3.

Antibacterial activity
An antibacterial activity of synthesised compounds 3a-g, 4a-g and 5a-g were determined in vitro against two bacterial species E. coli and B. subtilis.By using agar well diffusion method, bacterial species were cultured on nutrient agar plates at 37 o C. Plate containing 20 ml of nutrient agar was spread with 100 µl of culture.The wells were made in the agar cork boarer of width of 6 mm.The 100 µl of test compounds were loaded in the well along with amphicilin as positive control and DMSO as vehicle control.The plates incubated at 37 o C for 24 hours.Growth was evaluated visually by comparing a test plate with the control plates.The figures in Table-II indicates inhibition zone in mm and these are the mean of triplicate assays.

RESULT ANd dISCUSSION
Synthesised compounds 3a-g were obtained from the thiazole anchored molecule 1 and 3-formyl chromone 2. The yield of 3a-g compounds were in the range of 60-70%.The FTIR spectra of 3d shown peak at 3105 and 1654 cm -1 indicated the presence of Ar-OH and C=O groups in molecule.Whereas, the NMR spectra of 3d show the two singlets at δ 2.37 & 10.88 indicated the presence of Ar-CH 3 and Ar-OH.The compounds 4a-g were obtained from the compounds 3a-g and hydroxylamine hydrochloride by stirring at room temperature, practical yield of 4a-g compounds were in the range of 55-65%.From the FTIR spectra of 4d, the appearance of peak at 3085 cm -1 indicated the presence of Ar-OH and the disappearance of peak at 1654 cm -1 shown the absence of C=O group.The NMR spectra of 4d shown one singlet at δ 9.98 indicated the presence of -OH group of oxime.The compounds 5a-g were obtained from the refluxing the compounds 4a-g in POCl 3 , yield in the range of 50-60%.The disappearance of IR peak at 3085 cm -1 shown the absence of Ar-OH in 5d.In the NMR spectra of 5d, absence of two singlet at δ 9.98 and 11.88 of N-OH & Ar-OH, confirmed the formation of compound 5d.Mass spectroscopy also supported for the formation of 3a-g, 4a-g and 5a-g compounds.Physical characterised data of synthesised compounds are given in the Table -

ACkNOWLEdgEMENT
The authors are thankful to the P.G.Department of Chemistry, Radhabai Kale Mahila Mahavidyalaya, Ahmednagar and Department of Chemistry, New Arts, Commerce and Science College, Parner, Ahmednagar for providing chemicals.Authors are also thankful to the Management of Anekant Education Society, Baramati, Pune for providing necessary research facilities moreover to the Directors, SAIF and CIL, Panjab university, Chandigarh for providing the spectral and analytical data.

1 H
NMR spectra were recorded on Bruker Avance II 400 MHz spectrometer with DMSO-d 6 as a solvent and using TMS as internal standard.Chemical shift (δ) values are expressed in ppm.