Synthesis , Characterization and Biological Evaluation of Some Novel Thiophene Anchored Fluorinated Heterocycles

A new series of thiophene anchored 1,3,4-thiadiazole, 1,2,4-triazole, 2-heteryl chromone, 1,5-benzothiazepine, pyrazoline, 2-styryl chromone derivatives containing fluorine are synthesized, characterized by spectral methods and screened them for various biological activities.


INTRODUCTION
Thiophene is sulfur containing five membered heterocyclic compound widely used as building block in agrochemicals 1 .Thiophene containing compounds exhibit antimicrobial 2 , antiparasitic 3 , anticancer 4 and anticonvulsant 5 activities.
The activities associated with these various heterocycles prompted us to synthesize some novel thiophene anchored fluorinated heterocycles.

Biological activities Antimicrobial activity
Synthesized compounds were screened for their antifungal and antibacterial activities.The in vitro antimicrobial activities of the synthesized compounds were assessed against fungi and bacteria.The fungi used were C. albicans, A. Fumigatus and A. Niger.The bacterias used were S. aureus, E. coli, S. Epidermidis and P. Vulgaris.
Fluconazole and Amikacin were used as standards for comparison for antifungal and antibacterial activities respectively.The activities were determined by measuring the diameter of the inhibition zone in mm.
None of the compounds is a suitable candidate for antifungal and antibacterial indication as shown in Table 2.

EXPERIMENTAL
Melting points were recorded in open capillaries in liquid paraffin bath and are uncorrected.IR spectra were recorded on Perkin-Elmer FTIR spectrophotometer in KBr disc. 1 H NMR spectra were recorded on Bruker 400 MHz NMR spectrometer in DMSO as a solvent and TMS as an internal standard.Peak values are shown in ´ (ppm).Mass spectra were recorded on Finnigan mass spectrometer.

2-{[4-Bromo-5-(methylsulfanyl)thiophen-2yl]carbonyl}-N-phenylhydrazinecarbothioamide 2
Equimolar amounts (0.01 mole) of compound 1 and aryl isothiocyanate were dissolved in 15 mL of ethanol.The reaction mixture was heated under reflux for 55 minutes.The progress of reaction was monitored by TLC.After completion of reaction the contents were cooled and the solid obtained was filtered and crystallized from ethanol to get compound 2.

5-(4-Bromo-5-(methylthio)thiophen-2-yl)-4phenyl-4H-1,2,4-triazole-3-thiol 4
A mixture of thiosemicarbazide 2 and 10 mL of 1N NaOH was heated under mild reflux for 1.5 hr.The progress of reaction was monitored by TLC.After completion of reaction the contents were cooled and poured into crushed ice.Then it was acidified with glacial acetic acid.The product was separated by filtration and crystallized from the mixture (1:1) of DMF and water to get corresponding triazole 4.

10a
IR (KBr, cm -1  Compound 10 (0.003 mol) was taken in 100 mL RBF with 15 mL dioxane.To this reaction mixture 1 mL hydrazine hydrate was added and the contents were heated under refluxed for 4 hours.Then to the reaction mixture 2 mL gl.acetic acid was and heating was continued for further 3 hours.After complete heating contents were cooled to room temperature and poured over crushed ice.The solid thus obtained was separated by filtration and crystallized with alcohol to get compounds 12. Products obtained were identified with help of spectral data.Their characterization data is given in the Table -

2-((E)-2-(1-(4-Fluorophenyl)-3-(thiophen-2-yl)-1Hpyrazol-4-yl)-2,3-dihydrobenzo[b][1,4]thiazepin-4yl)phenol 13.
Compound 10 (0.001 mol) and o-amino thiophenol (0.001 mol) was suspended in 10 ml ethanol.Reaction mass was heated to reflux at 90 0 C for 4-5h.To the reaction mixture 2 ml glacial acetic acid was added and heating continued for further 3h.Contents were cooled and poured into crushed ice.The product obtained was separated by filtration and crystallized from ethanol.Products obtained were identified with help of spectral data.Their characterization data is given in the Table -  acetophenone were taken in dry beaker.To this mixture was dissolved in 15 ml dry pyridine.The reaction mixture was then cooled to 0 0 C. To this reaction mixture POCl 3 (0.06 moles) was added drop wise maintaining temperature below 10 0 C. Then reaction mixture was kept overnight at room temperature.It was then poured over crushed ice with vigorous stirring.Product was separated by filtration, washed with ice-cold water and then with 2% ice-cold solution of NaOH followed by ice-cold water again.Compound 15 (0.03 moles) was dissolved in 15 ml of dry pyridine.To this mixture powdered KOH (1 gm) was added and the reaction mixture was stirred on the magnetic stirrer for 3 hours.Then it was poured over crushed ice and acidified with acetic acid.The product was then separated by filtration, washed with water, dried and crystallized with acetic acid to afford 16.