Synthesis and Characterization of Some Fluorinated 1 , 5-Benzothiazepines and Pyrazolines

4-Bromo-2-fluorobenzaldehyde 1 when treated with substituted hydroxy acetophenones 2 yields chalcones 3. These chalcones were refluxed with 2-aminothiophenol gave “2-[2-(4bromo-2-fluorophenyl)-2,3-dihydro-1,5-benzothiazepin-4-yl]phenol” 4 and when treated with hydrazine hydrate gave the compound “2-[5-(4-bromo-2-fluorophenyl)-4,5-dihydro-1H-pyrazol3-yl]phenol” 5. The structures of compounds have been established on the basis of spectral data.


INTRODUCTION
One of the most important factors in the drug design is that fluorine is much more lipophilic than hydrogen, so incorporating fluorine in the molecule makes it more fat soluble, so it percolates into the membrane more readily and hence fluorinated molecule has a higher bioavailability.Around fifth of all drugs on the market today contain at least one fluorine atom such as Paroxetine, Ezetimibe, Linezolid and Midazolam.Many fluorinated compounds are widely used as antimalarial, antiviral, antipsychotic and antidepressants.Some heterocyclic compounds also act as dyes, pesticides, luminophores and herbicides in nature 1 .Various biological activities associated with chalcones includes antimitotic 2 , antiinvasive 3,4 , antifungal 5 , antituberculosis 6 , antileishmanial 7 , anti-malarial 8,9 , antiinflammatory [10][11][12] , antitumor and antioxidant properties 13 .Their recognized synthetic utility in the preparation of pharmacologically interesting heterocycles as pyrazolines, which includes antiparasitary 14 , anti-tumor 15 , nitric oxide synthase inhibitors 16 and anti-inflammatory 17 activities.

Present work
Substituted hydroxy acetophenones 2 on reaction with 4-bromo-2-fluorobenzaldehyde 1 stirred at room temperature for 24 hrs gives respective chalcones 3 which on reaction with 2amino thiophenol & reflux for 8 hrs gave benzothiazepines 4 and with hydrazine hydrate for 6 hrs which gave pyrazolines 5.

EXPERIMENTAL
All the recorded melting points were determined in open capillary tubes and are uncorrected.I.R. spectra were recorded on Shimadzu FTIR Spectrophotometer in KBr disc. 1 H NMR spectra were recorded on a Bruker Avance II 400 MHz spectrophotometer DMSO-d 6 as a solvent and TMS as an internal standard (chemical shift in  values).Mass spectra were obtained on a Finnigan mass spectrometer.Purity of the compounds was checked by TLC on silica gel G plates.

Synthesis of Chalcones
Compound 2 (0.005 mol) & 1 (0.005 mol) were taken in 100 ml RBF with 25 ml ethanol.To this reaction 2 gm of KOH was added & resulting reaction was stirred at room temperature for 24 hrs.Then contents were poured over crushed ice & acidified with conc.HCl, solid thus obtained were separated by filtration & crystallized from ethanol to get compound 3. Their characterization data is in the table-1(3a-3e).

Synthesis of Benzothiazepines
Compound 3 was dissolved in minimum quantity of ethanol.To this, 4-6 drops of 2aminothiophenol was added and the resulting reaction was refluxed for 4 hrs.Then reaction mixture was acidified by using 2 ml acetic acid and heating was continued for next 4 hrs.After cooling pale yellow crystals 4 were obtained.These were filtered