Synthesis of Some Novel Chalcone containing Pyrazole Moiety

 

V. A. Modhavadiya

Department of Chemistry, Shree M. M. Science college, Morbi-363642

 Saurashtra University, Rajkot, Gujarat India

*CorrespondingAuthorE-mail:drvasta20@gmail.com

Compounds having the sulphonamide group has long been used as drugs for various diseases. The biological activity of these drugs is enhanced by complexation with metal ions. Transition metal Fe (II) complex of ligand derived from sulfamethizole and substituted p-cresol have been prepared and evaluated for antimicrobial activity. The products have been characterized by elemental analysis, IR, NMR, UV-Vis spectral studies, conductivity measurements, magnetic   susceptibility measurements, molecular weight determination and stepwise stability constants by P^H metric method. The elemental analysis revealed that the azo dye ligand coordinated to the metal ions in 1:2 (metal-ligand) molar ratios. The complex are non-electrolytes as confirmed by their conductivity measurements. The infrared data indicates that the ligand are coordinated with meal ions through diazo (-N=N-) nitrogen and phenolic (-OH) oxygen. The spectral data suggest distorted octahedral geometry as shown in the proposed structure.

 

 

 

INTRODUCTION:

The sulfa drugs containing sulfonamide group                     (-SO₂NH-) and they are synthetic antimicrobial agents with a wide spectrum encompassing most gram-positive and gram-negative organisms^1-7. These drugs were the first efficient treatment to be employed systematically for the prevention and cure of bacterial infections^8-9.Chemists have taken a growing interest in the synthesis and physico-chemical studies of first row transition metal complexes with a number of azo dye ligand^10-11 during last few years. Metal complexes of azo dye ligand have played a central role in the development of co-ordination chemistry.

 

General structure of azo dyes are R-N=N-R’, where R and R’ are alkyl, aryl or hetrocyclic radicals. Most of them are prepared by the condensation of azo compounds with hydroxy aldehydes or ketones. Several bidentate azo dyes in which the phenolic –OH group and azo nitrogen are present in such a way that they form six membered ring with metal ions. Azo dyes have been investigated by many workers as chelating agent and their metal chelates and complexes have been extensively used in dyeing industry ^12-14 and studied dyeing properties^15-16.

 

Azo dyes are well known for their antiseptic activity^17-18 and some are useful as chemotherapeutic agents¹⁹. Transition metals like Fe, Co, Au, Ag, Cu, and Ni have long been used in medicine. A large number of metal sulphonamide complexes are found to be more potent than parent sulphonamides^20-21. In view of getting potent therapeutic agents present paper reports the synthesis of titled compounds.

 

MATERIALS AND METHODS:

Chemicals and reagents:

Most of the special chemicals used were purchase from British Drug House (BDH) Ltd. and E. Merck grade. They were: p-cresol, acetic anhydride, pyridine, anhydrous aluminum chloride, zinc dust, HgCl₂, Conc. HCl, NaNo₂ and FeSO₄. The bacterial strains used are two Gram positive bacteria: Bacillus megaterium, Bacillus subtilis and Gram negative bacteria: Escherichia coli, Acrobactor arogens. The fungal strains used are Aspergillus awamori, and Aspergillus niger.

 

The titled compounds  have been synthesized by the reaction of alcoholic solution of 3-ethyl-2-hydroxy-5-methyl-4’-( 5”- methyl-1”,3”,4” – thiadiazol -2”-yl ) Aminosulphonyl azobenzene   (ligand) with aqueous solution of Fe (II) metal salts. The later of ligand have been synthesized by coupling of diazotized sulfamethizole with 2-ethyl-4-methyl phenol. Earlier 2-ethyl-4-methyl phenol  have been synthesized by the clemmensen reduction^22-23 (Zn/Hg, Conc. HCl) on 2-acetyl-4-methyl phenol. The later was synthesized by the fries migration²⁴ of P-cresyl acetate have been synthesized by the acetylation²⁵ of P-cresol with acetic anhydride in presence of pyridine.

 

Preparation of the ligand :                              

Synthesis of 3-ethyl-2-hydroxy-5-methyl-4’-(5”- methyl-1”,3”,4”– thiadiazol -2”-yl) Aminosulphonyl azobenzene   (Azo dye ligand): Sulfamethizoie (0.025M) was taken in 10 ml HCl (0.055M) solution, and it was added to sodium nitrite solution 20 ml (0.025M) and the mixture was cool in ice bath. In another flask 2-ethyl-4-methyl phenol (0.025M) dissolved in 10 ml (0.025M) NaOH and cooled to 0° C. In situ Diazonium chloride of sulfamethizole was coupled with  2-ethyl-4-methyl phenol ( in above solution ) by adding drop wise at 0° C with constant stirring  and  keeping the P^H of the solution neutral. The product so obtained was recrystallised from alcohol.

 

Preparation of the metal complex :

The complex of Iron (II)  prepared by refluxing the mixture of alcoholic solution of azo dye ligand (2M) i.e. 3-ethyl-2-hydroxy-5-methyl-4’-(5”- methyl-1”,3”,4”– thiadiazol -2”-yl ) Aminosulphonyl azobenzene and metal salt solution (1M) for two hours in presence of excess of ammonium hydroxide and glacial acetic acid (PH=6.0 - 7.0).The complex were recrystallised from alcohol. The complex has decomposition temperature more than 210° C.

 

The structure of azo dye ligand (V) and proposed structure of Fe (II) metal complex (VI) are as under.

 

RESULTS AND DISCUSSION:

IR Spectral data of the ligand.

IR ( KBr ): 3440 (N-H str. and O-H str.), 3045 ( = C-H str.), 2966 (C-H str.-CH₃),2926 (C-H str.-CH₂ ), 2870 (C-H str.sym.-CH₃ ),2830(C-H str.sym-CH₂ ), 1610 (-N=N -str.),1563 (Thiadiazole ring str.),1546 ( N-H def.), 1469 (C=C str. ), 1417( C-H def. asym.,-N=N- and O-H def. ), 1310 ( S=O str.asym.), 1284(C-H i.p. def. disub. benzene), 1144 ( S=O str.sym.), 919 (Thiadiazole  ring skeletal), 844 ( C-H o.o.p. def.).

 

NMR Spectral data of the ligand.

¹H NMR (CDCl₃): 1.20-1.25 δ(3H,t,-CH₂ - CH₃ ),2.34 δ(3H,s,-Ar - CH_3, Phenyl ring.), 2.53 δ(3H,s, - CH_3,  Thiadiazole  ring. ), 2.66-2.69 δ(2H,q,-CH₂ - CH₃ ), 7.09 δ ( 1H, s, Ar-H ), 7.54 δ ( 1H, s, Ar-H ),7.85-7.87 δ ( 2H, d, Ar-H ),8.02-8.05 δ ( 2H, d, Ar-H ), 12.91 (1H,s,Ar-OH ).

 

Mass Spectra: (m/z): 418 (M⁺), 303, 287, 267, 255, 239, 223, 205, 195, 163, 150, 135, 120, 105, 91, 77, 65, 55, 41.

 

Absorption Spectra:  λ max (nm): 230, 249, 324, 363.

 

log ε : 4.3226, 4.3170, 4.2610, 4.3145.

 

Antimicrobial Activity:

The testing were carried out by cup-plate method^26-28 at a concentration of 50 μg using gram positive bacteria as B. megaterium and B. subtilis and gram negative bacteria as E. coli.  and P. fluorescens and fungi as A. awamori and A.niger.  Most of the compounds were moderately active against different strains of bacteria and fungi. However, comparatively significant  was observed in compounds

(along with zone of inhibition in mm) having azodye ligand  (V)-(18), Fe ( II ) complex (VI)-(19) against B. megaterium,  azodye ligand  (V)-(22), Fe ( II ) complex (VI)-(18) against B. subtilis, azodye ligand  (V)-(25), Fe ( II ) complex (VI)-(16) against E. coli., azodye ligand  (V)-(20), Fe ( II ) complex (VI)-(21) against A. arogens, azodye ligand  (V)-(19), Fe ( II ) complex (VI)-(16) against A. awamori, azodye ligand  (V)-(20), Fe ( II ) complex (VI)-(19) against A. niger.

 

Physical Measurements:

Elemental analysis for C and H were estimated on a cooleman analyzer and N was estimated by Kjeldahl’s method. The percentages of metals were determined by EDTA complexometric²⁹ titration. Molar conductivities of 10^-3 M solutions of the complexes in DMF were measured on a Toshniwal conductivity bridge using a dip type cell at room temperature. Magnetic susceptibilities were measured at room temperature on a Gouy balance using mercury (II) tetrathiocynato cobaltate (II) as the calibrant.  All results are given in Table-1.

 

P^H-metric measurements:

For the determination of stepwise stability constants an expanded scale Systronic P^H meter with accuracy ±0.02 units was employed. All experiments were carried out at 30 ± 0.2 ⁰C and temperature was mentioned constant using thermostat. The three sets acid, acid + ligand, acid + ligand + metal were prepared.

 

In each case total volume was made up to 40 ml by adding required amount of double distilled water or purified dioxane as the case may be. The ionic strength was maintained by adding appropriate amount of sodium nitrate (0.01M) and mixtures were titrated with standard NaOH solution. A modified form of Irving-Rosstti³⁰  titration technique was used for calculating the stability constants. The P^H meter was calibrated with aqueous buffers. In the calculations for pL the pH meter reading ‘B’ was used instead of converting it to true pH value (Corresponding to aqueous medium). The use of pH meter reading ‘B’ instead of true pH values did not make any differencesin the calculation of free ligand concentration and was usually valid for water dioxane media. The results are shown in table-2.

 

 

Table-1: The elemental analysis, conductometric analysis and magnetic susceptibility of metal complex  

 

 

 

Table 2: Stepwise stability constants of metal complexes of 3-ethyl-2-hydroxy-5-methyl-4’-(5”-methyl-1”,3”,4”–thiadiazol-2”-yl) Aminosulphonyl azobenzene  in ( 60 : 40 ) Dioxane :Water, μ  =0.1M, Temp 30 ± 0.2⁰ C.

Ligand	logK1H	logK2H	logB2H
C18H19O3N5S2	10.720	3.605	14.325
Complex	logK1	logK2	logB2
Fe(C18H18O3N5S2)2 (H2O)2	7.232	5.204	12.436

 

CONCLUSION:

According to above observation, the Fe (II) complex structure has been proposed as shown at earlier (VI), distorted octahedral. The Mossbauer spectra shows two symmetrical bands indicating distorted octahedral geometry which is support of the fact that there are two water molecules attached with Fe (II) metal ions. The ratios of metal to ligand are 1:2 in the metal complexes as confirmed by their elemental analysis. The in vitro antimicrobial screening of the complex confirmed their potency against most of the microorganisms used in this study. The complex is non-electrolytes as confirmed by their conductivity measurements.

 

ACKNOWLEDGDMENTS:

 The author is thankful to Late Dr. G.K. Joshi for valuable guidance and  Head, Department of Chemistry, Saurashtra University, Rajkot, India for providing the necessary laboratory facilities.

 

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Received on 25.01.2018         Modified on 30.01.2018

Accepted on 03.02.2018         © AJRC All right reserved