Synthesis and Screening of Fluoro Substituted Pyrazolyl Benzoxazoles

A series of 3-Formylchromone 1 was reacted with 1-(4-(4-fluorophenyl)thiazol-2-yl)hydrazine 2 to get (1-(4-(4-fluorophenyl)thiazol-2-yl)-1H-pyrazol-4-yl)(2-hydroxyphenyl) methanone 3 which on reaction with hydroxylamine hydrochloride given methanone oxime 4 and 4 on treatment with POCl3 formed 2-(1-(4-(4-fluorophenyl)thiazol-2-yl)-1H-pyrazol-4-yl)benzo[d]oxazole 5. The structures of synthesized compounds were confirmed by spectral analysis further they were screened for their biological activity.


INTRODUCTION
3-Formylchromones give several versatile condensation reactions as they contain 3electrophilic centers in the molecule 1 which can be converted into various biological active compounds.3-Formylchromones achieved by the most stable method through the application of Vilsmeir Haack reaction 1, 2 from 2-hydroxyacetophenone.It has an instantaneous aldehyde group and undergoes Knovengel condensation reaction and gives several important synthetic compounds.Different researchers were studying the condensation reactions of various nucleophiles with 3formylchromones.2-Hydroxyacetophenones are good precursors for several applications, which were synthesized by Fries rearrangement by known procedure 3 .
Pyrazole nucleus based compounds exhibits focus on medicinal and agriculture chemistry because they found vast scope for biological activities like antitumor and anti-HCV agents 4 , hepatoprotective 5 , antidiabetic6, anticancer 6 , cytotoxic 7 , herbicidal 8 and fungicidal 9 activities.Fluorinated moieties have been found unique properties in synthesizing the compounds in the drug world.
Methanones are effective inhibitors of FLT3-ITD kinase in vitro and stimulate apoptosis in PKC412 sensitive and resistant cell lines 10 .Many of them are also shown extensive band of bioactivities such as antimycobacterial 11 , antipsychotic 12 , antioxidant 13 , antifeedant 13 , they are effective inducer of apoptosis 14 .Oximes are being extensively used as an important intermediate in synthesizing the new heterocycles.Oximes shows acaricidal 15 , insecticidal 16 , antiviral (TMV) 17 and antimicrobial 18,19 activities.Benzo-fused bicyclic hetero ring structure possess tempting pharmacological activities.Substituted benzoxazole derivatives show anti-HIV 20 , antitubercular 21 , anticonvulsant 22 and antiproliferative 23 activities.Benzoxazole is an antiallergic compound which inhibits the release of mediators of allergic reaction.Benzoxazole also shows two fold 5-Lipoxygenase and Cycloxygenase inhibitors with anti-inflammatory action 24 .
Due to the extensive applications and biological activities allied with fluorine, pyrazole, benzoxazoles and the utility of oximes as an important intermediate provoked us to synthesize the variously substituted fluorine containing benzoxazole derivatives.

Biological activities Antimicrobial activity
13 synthesized compounds were evaluated for their antibacterial activity against the bacteria E. coli, Pseudomonas aeruginosa and Staphylococcus aureus using standard drugs like Gentamycin and Nystatin.The activities were studied by turbidity method using DMSO as a solvent.The Inhibition zones were measured in mm.The same compounds were also tested for fungal activities against the fungus Candida sp. using the same standard drugs in the same solvent as for antibacterial activities.The used concentration was 1mg/1000mm.At this concentration no activity was observed.

EXPERIMENTAL
The Physical constant of all the synthesized compounds were measured in open capillary tubes in paraffin liquid and are uncorrected.Purity of all synthesized compounds was checked by TLC.The IR spectral study was recorded on a Perkin-Elmer (spectrum on a FT-IR) spectrometer.The 1 H NMR was studied on a BRUKER AVANCE II 400 MHz NMR Spectrometer in CDCl 3 and DMSO as a solvent, chemical shift () were expressed in ppm (scale) downfield from TMS and coupling constant (J) are expressed in hertz (Hz).Mass spectra were recorded on Waters, Q-TOF MICROMASS (LC-MS).TLC was performed on precoated silica plates, which was experiencing under UV illumination.All the synthesized compounds gave an adequate elemental analysis. (

1-(4-(4-Fluorophenyl)thiazol-2-yl)-1H-pyrazol-4yl)(2-hydroxyphenyl)methanone
3-Formylchromone (0.02 mole) was dissolved in ethanol with 1-(4-(4-fluorophenyl) thiazol-2-yl) hydrazine (0.02 mole).The reaction mixture was reflux for 30 min to get analogous hydrazone.To the same reaction mixture 22 moles of KOH were added and heating was sustained for a further 6 hr.After finishing point of the reaction the contents were cooled to room temperature and poured into crushed ice.The ensuing solution was neutralized by means of conc.HCl.The solid obtained was separated by filtration and crystallized from ethanol.Compounds synthesized by the above reaction procedure are listed in Table 1.