A Facile Solvent Free Microwave Induced Synthesis and Antibacterial Activity of Some 3-( 2 ’-Hydroxyphenyl )-5-( Substituted Aryl )-2-Pyrazoline-N 1-Caboxaldehydes

A novel one pot formylation of 3-(2’-hydroxyphenyl)-5-(substituted aryl) 2-pyrazolines has been carried out using microwave irradiation with formic acid. The solvent free reaction afforded title compounds in 80-90% yield with high purity. All synthesized compounds were tested for their antibacterial activity using standard drug.


Introduction
Pyrazolines and their derivatives are known to possess impressive biological activities.They have been reported to have bactericidal 1.2 , acarcidal 3,4 , anti inflammatory ,5 , antidepressant 6 , anipyretic 7 ,antibacterial 8 and antifungal 9 properties.Certain pyrazolines due to their non toxic properties have been used as local anesthetics also 10 .Recently reported studies on the microwave irradiation for the synthesis of heterocyclic compounds revealed that it is safe, rapid, economic and convenient, eco friendly method for chemical synthesis.Pollution free synthesis, lesser reaction time, easy workup, and minimum use of solvent are the major advantages of this technique [11][12][13] .A serious constrain of this method is selection of appropriate solvent, which can be avoided by synthesis under solid phase solvent free condition 14 .
These facts have prompted us to synthesis some new pyrazoline carboxaldehydes using microwave irradiation under solvent free condition .3-(2'-hydroxyphenyl)-5-(substitutedaryl)-2pyrazolines were treated with formic acid under microwave irradiation to afford the title compounds.Alternatively 2'-hydroxy Chalcones were heated with hydrazine hydrate in presence of formic acid under MWI to get the compound (3a-e).The identity of the synthesized compounds was established on the basis of co-TLC, m.m.ps, elemental analysis and spectral data.

Experimental
Melting points were measured on a Buchi 530 melting point apparatus in open capillaries and are uncorrected (Table 1).The purity of the compounds was checked by TLC using silica gel-G.adsorbent and benzene-ethyl acetate (9:1v/v) as the eluent.IR spectra were recorded on Pekin-Elmer1600 spectrometer using KBr (cm -1 ). 1 H-NMR spectra were taken on Brucker-DRx-600 Spectrometer using TMS as internal standard and CDCl 3 or DMSO-d 6 as solvent.Mass spectra were obtained on JEOL-SX-DA-600 mass spectrometer (FAB) using m-nitro benzyl alcohol as Matrix.Matrix peaks appeared at m/z 136,137,154,289 and 307.

Method -B
A slurry of 2'-hydroxy chalcone (0.05 mole), hydrazine.hydrate (0.05 moles) and formic acid (0.10 mole) was irradiated under microwave at 450 watt.for 5-6 minis.After completion of reaction as indicated by TLC, the reaction mixture was cooled to room temperature and extracted with ethanol.The separated solid on crystallization was identified as 3(a-e). (1)

Antibacterial Activity
All the synthesized compounds were screened for their antibacterial activity against gram positive S.aureus and S.albus and gram negative E.coli, K. pneumonia and P.vulgaris organism.In the determination of antibacterial activity peptone nutrient broth was used, the media was used for gram negative organism by adding 2% mecconkey agar to the nutrient broth and for gram positive organism it was prepared by adding 10% sheep blood to 2% nutrient agar.Paper disc diffusion plate method was followed by using special microbial filter paper disc.The compound were screened at maximum concentration of 250µg/mL in DMF.Results were compared with standard drug Amicacin and coffrioxane at concentration 30 µg/disc.The results of antibacterial activity were tabulated in the form of activity index (Table 2.)  -----------------------------------------------Zone of inhibition of std.drug in mm The observation show that Activiy index of compound 3a., 3b., 3c., 3e,. is maximum against Klebsiella pneumonia, compound 3a., 3e,.show good index against E.coli.All the compounds are inactive against gram positive S.aureus and S.albus

Table 2 .
Antibacterial activity of synthesized compounds