THIONYL CHLORIDE CATALYZED SYNTHESIS AND ANTIMICROBIAL ACTIVITIES OF SOME 2-BENZYLIDENE-1- TOSYLHYDRAZINES

Generally, sulphur substituted compounds have a significant role in developing pharmaceutical chemistry filed. Numerous medicinally important products are made up of heterocyclic sulphur compounds using challenging synthetic reproductions. Hydrazones and hydrazides are currently a significant class of therapeutically active compounds. 3 The suitable intermediates are produced by the heterocyclic hydrazone compounds like thiazolidin-4one or 1, 3-benzothiazin-4-one. Hydrazones can act as polydentate ligands, depending on the nature of the attached group of hydrazone substituent. In organic synthesis, sulphur containing hydrazones shows interesting pharmaceutical derivatives and essential intermediates. Pharmacophoric hydrazone derivatives are newly designed based on highly bio-activity, appear vital activity and biologically important position. The interesting and valuable field for variety of heterocyclic compounds prepared from sulphur hydrazides, because they have medication active like antibacterial, exhibit a great interest due to their importance in synthesis a which have antifungal, antiinflammatory herbicidal, inhibitory activity, analgesic activity, anticholinergic and antihistaminic, activity of regulating growth in plant etc. Within the above view, no information available in literature in the past for synthesis and infectious activities of 2-benzylidene-1-tosylhydrazines. Therefore, the authors have taken efforts for the synthesis of some substituted 2-benzylidene-1-tosylhydrazines and studied the antibacterial and antifungal activities by BauerKirby disc diffusion method. EXPERIMENTAL


INTRODUCTION
Generally, sulphur substituted compounds have a significant role in developing pharmaceutical chemistry filed. 1 Numerous medicinally important products are made up of heterocyclic sulphur compounds using challenging synthetic reproductions.Hydrazones and hydrazides are currently a significant class of therapeutically active compounds. 2,3 he suitable intermediates are produced by the heterocyclic hydrazone compounds like thiazolidin-4one 4 or 1, 3-benzothiazin-4-one. 5 Hydrazones can act as polydentate ligands, depending on the nature of the attached group of hydrazone substituent.In organic synthesis, sulphur containing hydrazones shows interesting pharmaceutical derivatives and essential intermediates. 6harmacophoric hydrazone derivatives are newly designed based on highly bio-activity, appear vital activity and biologically important position.The interesting and valuable field for variety of heterocyclic compounds prepared from sulphur hydrazides, because they have medication active like antibacterial, 7 exhibit a great interest due to their importance in synthesis a which have antifungal, 8 antiinflammatory 9 herbicidal, 10 inhibitory activity, 11 analgesic activity, 12 anticholinergic and antihistaminic, 13 activity of regulating growth in plant 14 etc.Within the above view, no information available in literature in the past for synthesis and infectious activities of 2-benzylidene-1-tosylhydrazines.Therefore, the authors have taken efforts for the synthesis of some substituted 2-benzylidene-1-tosylhydrazines and studied the antibacterial and antifungal activities by Bauer-Kirby 15 disc diffusion method.

Materials and Methods
All chemicals procured from the chemical company of Aldrich Bangalore.To detect the melting points of all prepared tosylhydrazines are found in Suntex melting point apparatus with capillary tubes.The ultraviolet spectra of the tosylhydrazines synthesized have been noted using double beam-ELICO BL222 Bio-Spectrophotometer.Fourier transform infrared spectra (KBr, 4000-400 cm -1 ) have been documented on AVATAR-300 FT-IR spectrophotometer.The BRUKER-500MHz NMR spectrometers were used for noted proton and 13 C spectra in the CDCl3 solvent using tetramethylsilane as internal standard.Microanalysis of all compounds was performed in Thermofinnigan CHN analyzer.

Synthesis of 2-benzylidene-1-tosylhydrazines
The appropriate mixture of 1-tosylhydrazine (100 mmol) and ortho, meta and para substituted benzaldehydes (100 mmol), 15 mL of diethyl ether and (100 mmol) of thionyl chloride were added.The reaction content was vigorously agitated at normal temperature for 30 minutes 16 (Scheme 1).After complete renovation of the tosylhydrazines as monitored by thin layer chromatogram, the mixture may allow to 20 minutes for an undisturbed condition.The method of filtration is used to the removal of unreacted reagents.The crude product was cleaned with deionized water and recrystallized from absolute ethanol, dried well and kept in a desiccator.The synthesized 2-benzylidene-1tosylhydrazines have been regarded as by their physical constants, elemental analysis, and spectroscopic data and are presented in Table 1.The ultraviolet, infrared and nuclear magnetic resonance spectroscopic data of synthesized 2benzylidene-1-tosylhydrazines are shown in Table 2.

Antibacterial sensitivity assay
Antibacterial sensitivity assay has been accomplished using Kirby-Bauer 15-17 disc diffusion technique.In each Petri plate, about 0.5 cm 3 the sterile glass spreader are used to spread the sample of test bacteria to over the medium uniformly at solidified Mueller-Hinton agar.The sterile forceps are used to impregnated by Whatman No.1 filter paper (5 mm diameter), the compound containing the solution to place the medium.To avoid the water droplets collection on plates upside down over the medium, to incubated at 37 °C for 24 hours.The inhibition zone values of diameter are visually surveyed after 24 hours at the plates.Same procedure is used to measure for triplicate values.
The synthesized 2-benzylidene-1-tosylhydrazines compounds are screened for the antibacterial study is shown in Figure S1 (Plates 1-20) (See supplementary material 1).Following four gram-positive bacterial strains S. Aureus, 17 S. Pyogenes, 18 M. Luteus, 19 B. Substilis 20,21 and six gramnegative strains K. Pneumoniae, 22 V. Parahaemdyticus, 23 K. Oxytoca, 24 P. Mirabili, 25 E. Coli, 26 P. Aeruginosa 27 are used for antibacterial study of all the synthesized 2-benzylidene-1-tosylhydrazines.The technique of disc diffusion was followed at a concentration of 250 μg mL -1 with Ciprofloxacin taken as the standard.The inhibition zone values are used to compare in Table 3 is the corresponding chart of clustered column is shown in Figure 1.
Analysis of the inhibition zone (mm) values reveals that the all the substituted 2-benzylidene-1-tosylhydrazines compounds were shown satisfactory antibacterial action S. Aureus bacterial strain except 2-chloro substituent.The inhibition zone (mm) values reveal that the all the substituted 2-benzylidene-1-tosylhydrazines compounds were shown satisfactory and good antibacterial action against S. Pyogenes bacterial strain except for 4-fluoro and 3-nitro substituents.
The inhibition zone (mm) values reveals that the benzohydrazide compounds have shown satisfactory and moderate antibacterial activity against M. Luteus bacterial strain.The inhibition zone (mm) values reveal that the substituted 2-benzylidene-1-tosylhydrazines compounds have shown satisfactory antibacterial activity against M. Luteus bacterial strain except for 2-chloro, 4fluoro, and 2-nitro substituents.The 2-nitro substituted 2-benzylidene-1-tosylhydrazines compound shown good antibacterial activity and remaining substituted 2-benzylidene-1-tosylhydrazines compounds have a good antibacterial action against K. Pneumoniae bacterial strain except for 3-nitro substituent.
The inhibition zone (mm) values reveal that the 2benzylidene-1-tosylhydrazines compounds have been shown moderate antibacterial action against V. Parahaemdyticus bacterial strain except for 4-methyl substituent.The inhibition zone (mm) values reveal that the 2-benzylidene-1-tosylhydrazines compounds have shown satisfactory antibacterial action against K. Oxytoca bacterial strain except for 4-chloro and 4-methyl substituents.The inhibition zone (mm) values reveal that the 2-benzylidene-1tosylhydrazines compounds have been shown satisfactory and moderate antibacterial action against P. Mirabilis bacterial strain except for 4-hydroxy substituent.The 4chloro and 3-hydroxy substitute 2-benzylidene-1tosylhydrazines compounds have been shown good antibacterial activity, and remaining substituents have moderate antibacterial activity against E. Coli bacterial strain.The inhibition zone (mm) values reveal that the 2benzylidene-1-tosylhydrazines compounds have shown

Antifungal sensitivity assay
Antifungal sensitivity assay has been performed using Kirby-Bauer 15 disc diffusion technique.PDA medium is prepared and then sterilized as stated earlier.The fungal species containing (1 mL) Petri-plate then poured PDA medium in ear bearing heating condition.[32] The species are spreading over the plates uniformly using clockwise and anti-clockwise rotations.The about 15 mg sample is used to prepare the test solution of substituted 2benzylidene-1-tosylhydrazines in DMSO solvent (1 mL).The impregnation is followed by the disc in the test solution.The medium has been permitted to solidify and kept for 24 hours.
The inhibition zone values of the plates have been examined and measured the diameters.The results had been recorded by the triplicate and repeating the same procedure.The antifungal action of substituted (2-benzylidene-1tosylhydrazines compounds had been studied and are shown in Figure S2 for Plates (21-26) (See supplementary material 2), and the inhibition zone value of the effect is given in Table 4.The chart clustered column, shown in Figure 2.

No. X Zone of inhibition(mm)
A. Niger M. Species T. Viride
Analysis of the inhibition zone (mm) values reveals that the substituted 2-benzylidene-1-tosylhydrazines compounds had shown satisfactory and moderate antifungal action against A. niger species.The inhibition zone (mm) values reveal that the substituted 2-benzylidene-1-tosylhydrazines compounds have shown satisfactory antifungal activity against M. species fungal species except for 4-hydroxy and 4-methyl substituents.The zone of inhibition (mm) values reveals that the substituted 2-benzylidene-1-tosylhydrazines compounds had shown satisfactory antifungal action against T.viridie fungal species.

Table 1 .
Physical constants, yield and analytical data of substituted 2-benzylidene-1-tosylhydrazines Values in the parenthesis are calculated