INTRODUCTION:

Although the hexadentate ONS-donor ligand 1,2-di-(O-Salicylaldimino phenyl thio ethane) and its. Coblt (III) complex were first reported by Dwyer et al⁽¹⁾ and cannon et al⁽²⁾. Later on Dey et al⁽³⁾ reported complexes of hexadentate ONS donor ligand with Ni (II), Cu (II), Co (III) and Pd (II). Their characterization has been made on the basis of elemental analysis, IR and electronic spectra, molar conductance and magnetic moment data.

Here we report on the synthesis and characterization of a new set of binuclear and polynuclear Cu (II), Ni (II) and Co (II), Fe (II) complexes of 4, 4’ – bis (2-hydroxy aceto-phenoimine) – 3 – 3’-disubstituted diphenyl methane and 5-5’ methylene / dithio bis (salicylaldehyde) Hexane 1, 6-diamine.

MATERIAL AND METHOD:

4, 4’ – Diamino diphenyl methane was procured from M/s Fluka Chemicals. Its subsequent methoxylation, methylation and halogenation yielded the other diamines used in the preparation of ligand.

Preparation of ligands: The ligand was prepared by refluxing a mixture of 4, 4’ – Diamino diphenyl methane (0.1 mol) and ortho hydroxyl acetophenone (0.1 mol) in 50 ml of absolute alcohol containing 3 drops of concentrated sulphuric acid for three hours. The solid product obtained was separated and recrystallised from alcohol as yellow coloured needles (M.P. 170°C).

Isolation of Complexes

Copper (II) Complexes: To an ethanolic (50 ml) solution of 3, 3’-di-(x^-) substituted-4-4’- bis (Ortho hydroxy acetophenoeimino) diphenyl methane (X=H, CH₃, OCH₃, CI) (0.01 mol) was added with stirring a solution of metal acetate (0.01 mol) in ethanol and refluxed for 4-6 hours on water bath. The metal complexes that precipitated during reflux were filtered off washed thoroughly with ethanol and dried in vacuum desiccator over fused calcium chloride.

Ni (II) Complexes: (2N-NaOH) was added to the solution containing nickel (II) chloride in water acetone and the schiff base in methanol in 1:1 stoichiometric ratio⁽⁴⁾. Whole content was refluxed for two hours when yellowish green precipitate separated out. It was filtered washed with ethanol-water and dried under vacuum.

TABLE (1) ANALYTICAL DATA OF THE SYNTHESIZED COMPOUNDS:

S. No.	Compound	Colour	M. P. ^oC	% Chemical Analysis Found (Calculated)
S. No.	Compound	Colour	M. P. ^oC	C	H	N
1.	(C₂₉H₂₆N₂O₂)	Yellow	170	79.95 (80.18)	5.86 (5.99)	6.40 (6.45)
2.	(C₃₁H₃₀N₂O₂)	Yellow	173	80.10 (80.52)	6.26 (6.49)	6.0 (6.06)
3.	(C₃₁H₃₀N₂O₄)	Yellow	182	74.98 (75.30)	6.0 (6.07)	5.52 (5.67)
4.	(C₂₉H₂₆N₂O₂CI₂)	Yellow	186	68.93 (69.18)	4.70 (4.77)	5.46 (5.56)
5.	(C₂₁H₂₄N₂O₂)	Yellow	214	74.84 (75.0)	7.06 (7.14)	8.08 (8.33)
6.	(C₂₀H₂₂N₂O₂S₂)	Dark Yellow	222	62.01 (62.17)	5.10 (5.69)	7.03 (7.25)

Cobalt (II) complexes: Cobalt (II) acetate hexahydrate (0.005 mol) was dissolved in 50 ml methanol. A mixture of 4 - 4’ – Diamino diphenyl methane (substituted) and ortho hydroxy acetophenone (0.005 mol) was heated under reflux in methanol (40 ml) on a water bath for two hours. The Schiff base solution was added to the above Cobalt (II) acetate solution slowly with stirring and the mixture refluxed with magnetic stirring for two hour. The separated Bluish precipitates were filtered, washed with methanol and dried in vacuum at room temperature.

RESULTS AND DISCUSSION:

The analytical characteristics of synthesized chemicals were shown in table-1. The complexes are stable towards light and atmosphere. All the complexes are soluble in DMF and DMSO. The analytical data agree with the molecular formula is shown in table-2. The molar conductance of Cu (II), Ni (II) and Co (II) complexes indicate their non electrolytic nature in solution.

Cu (II) Complexes: The Cu (II) complex displays a single broad band in the region 14000-15000 cm^-1. There is also a low energy shoulder at ~1000 cm^-1 planar Schiff base, Copper (II) complexes are known to have only one band between 14000 and 16000 cm^-1 while tetrahedral Schiff base copper complexes are known to have absorption bands in the regions^(5,6) 12000 -14000 cm^-1 some pseudo tetrahedral copper (II) complexes have bands located^{(7, 8)} at as low positions at 11400 cm^-1 with an additional band is described to the d_x² – y ² "d_yx transition ⁽⁹⁾. In these complexes the l - max values of the spectral bands are in between the positions expected for proper planar or pseudo tetrahedral copper (II) complexes.

It is known for (R-N-Sal)₂ Cu type of complexes that distortion from planar to tetrahedral geometry increases as the R-group becomes bulkier. This shifts the absorption maxima to longer wavelengths ⁽¹⁰⁾. In the present complexes R-group is more rigid and bulkier hence distortion towards tetrahedral configuration result in the shifting of l - max values to longer wavelengths region in these complexes ⁽¹¹⁾.

Cobalt (II) complexes: Magnetic moment of the Cobalt (II) complexes fall in the range (4.30– 4.50) B.M. Although the m-effective values of high spin octahedral and high spin

tetrahedral cobalt complexes overlap considerably, tetrahedral complexes have generally low m-effective values often in the range 4.2 – 4.5 B.M. The m-effective value for the corresponding octahedral complexes fall around 4.8 B.M.⁽¹²⁾.

Complexes under study have magnetic moment value around (4.82 B.M.) showing octahedral environment around the Co (II) ion. The observed electronic spectra of Co (II) complex are typical of high spin octahedral species ^{(13, 14)}. The bands observed at 8403 and 19610 cm^-1 are attributed to ⁴T_1g (F) " ⁴T_2g (F) (v₁) and ⁴T_1g (F) " ⁴T_1g (P) (v₃) transitions respectively. The highest energy band around 30770 cm^-1 is assigned to a charge transfer transition.

Melting point of the compounds were determined by open capillary method which are uncorrected, the synthesized compounds are characterized by Elemental analysis, FT-IR and some selected compounds subjected to ¹H NMR in CDCl₃solvent , all the compounds are screened for antibacterial and antifungal activity.

General procedure for Chalcones:

A mixture of various substituted aromatic aldehydes [0.01 mol] and substituted aryl acetophenone [0.01 mol] was stirred in 30 ml of ethanol at the room temperature in the presence of 10 ml of 15 % KOH was added to the mixture. This mixture was stirred for 16 hr and kept for overnight at room temperature and then it was poured into crushed ice and acidified with dilute acids to neutral. The Chalcones derivatives are precipitates out as solid. Then it was filtered, dried and recrystallized from ethanol.

General procedure for synthesis of Isoxazole and Pyrazole derivatives:

A mixture of [0.016 M] of Chalcones with [0.012 M] of Hydroxyl amine hydrochloride was refluxed in 30 ml ethanol with 10 ml of sodium acetate on water bath for 22 hours this for isoxazole. For Pyrazole, the mixture of [0.01M] of Chalcones with [0.01M] of Hydrazine hydrate was refluxed in 30 ml ethanol with 10 ml of KOH on water bath for 24 hours. Then the reacting mixture was cooled and poured into crushed ice, the solid product was precipitate out, then it was filtered, dried and recrystallized from ethanol. The reaction is monitored by TLC. All the compounds are characterized by physical and spectral data as shown in table-1.

Table-1 Physical data for the synthesized compounds BJ (1-8).

Comp. Code	R¹	R²	Mol. Formula	Mol.Wt ( gms )	% Yied	M.P. ^oc	Calculated % of Elements
Comp. Code	R¹	R²	Mol. Formula	Mol.Wt ( gms )	% Yied	M.P. ^oc	C	H	N	O
BJ-1	4-CH₃	4-N(CH₃)₂	C₁₈H₁₈N₂O	278	86	188	77.67	6.52	10.06	5.75
BJ-2	4-NH₂	4-OH	C₁₅H₁₂N₂O₂	252	72	192	71.42	4.79	11.10	12.68
BJ-3	4-OCH₃	3-NO₂	C₁₆H₁₂N₂O₄	296	76	212	64.86	4.08	9.45	21.60
BJ-4	4-OCH₃	4-OH	C₁₆H₁₃NO₃	267	82	176	71.90	4.90	5.24	17.96
BJ-5	4-NH₂	4-OH	C₁₅H₁₅N₃O	253	76	198	71.13	5.97	16.59	6.32
BJ-6	4-NH₂	3-NO₂	C₁₅H₁₄N₄O₂	282	66	206	63.82	5.00	19.85	11.34
BJ-7	4-OCH₃	4-N(CH₃)₂	C₁₈H₂₁N₃O	295	70	226	73.19	7.17	14.23	5.42
BJ-8	4-CH₃	3-NO₂	C₁₆H₁₅N₃O₂	281	68	190	68.31	5.37	14.94	11.38

Scheme:-

Spectral data for the synthesized compounds BJ(1 – 8): ^10,11.

BJ-1: N,N-dimethyl-4-[3-(4-methylphenyl)-1,2-oxazol-5-yl]aniline,

IR (KBr) cm^-1: 1645 (C=C), 845 (N-O isoxazole), 1475 (C=N isoxazole).

BJ-2: 4-[3-(4-aminophenyl)-1,2-oxazol-5-yl]phenol,

IR (KBr) cm^-1: 1639 (C=C), 837 (N-O isoxazole), 1438 (C=N isoxazole).

BJ-3: 3-(4-methoxyphenyl)-5-(3-nitrophenyl)-1,2-oxazole,

IR (KBr) cm^-1: 1633 (C=C), 858 (N-O isoxazole), 1485 (C=N isoxazole). ¹H-NMR (CDCl₃ δ in ppm) 6.92 (s, 1H, -CH of isoxazole), 3.78 (s, 3H, -OCH₃). 8.12-7.58(m, 8H, Ar-H)

BJ-4: 4-[3-(4-methoxyphenyl)-1,2-oxazol-5-yl]phenol,

IR (KBr) cm^-1: 1633 (C=C), 842 (N-O isoxazole), 1464 (C=N isoxazole). ¹H-NMR (CDCl₃ δ in ppm) 6.87 (s, 1H, -CH of isoxazole), 3.72 (s, 3H, -OCH₃), 8.24-7.82(m, 8H, Ar-H), 11.1(s, 1H, OH).

BJ-5: 4-[3-(4-aminophenyl)-4,5-dihydro-1H-pyrazol-5-yl]phenol,

IR (KBr) cm^-1: 1622 (C=C), 1610 (C=N pyrazole), 3385 (NH pyrazole).¹H-NMR (CDCl₃ δ in ppm) 3.43(d, 2H, CH₂pyrazole), 8.4-7.9(m, 8H, Ar-H), 11.4 (s, 1H, OH).

BJ-6: 4-[5-(3-nitrophenyl)-4,5-dihydro-1H-pyrazol-3-yl]aniline,

IR (KBr) cm^-1: 1645 (C=C), 1582 (C=N pyrazole), 3412 (NH pyrazole).

BJ-7: 4-[3-(4-methoxyphenyl)-4,5-dihydro-1H-pyrazol-5-yl]-N,N-dimethylaniline,

IR (KBr) cm^-1: 1658 (C=C), 1568 (C=N pyrazole), 3394 (NH pyrazole). ¹H-NMR (CDCl₃ δ in ppm) 3.22(d, 2H, CH₂pyrazole), 8.1-7.4(m, 8H, Ar-H), 3.9(s, 3H, OCH₃).

BJ-8: 3-(4-methylphenyl)-5-(3-nitrophenyl)-4,5-dihydro-1H-pyrazole,

IR (KBr) cm^-1: 1668 (C=C), 1597 (C=N pyrazole), 3465 (NH pyrazole).

Biological activity ^{[ 8,9 ]}:

All synthesized compounds were screened for antibacterial and antifungal activity by cup plate method from the standard procedure; the two concentrations are taken i.e. 50 & 100 µg/ml over a different bacterial strains and fungal strains as shown in table. The values obtained is compared with the values produced from the standard drugs like Procaine penicillin, Streptomycin for bacterial and Griseofulvin for Fungal and the dimethyl form amide (DMF) was used as control for both the strains. Some of the compounds show significant property compared with the standard and other shows moderate. This will be shown in the table-2.

Table-2 Anti-Microbial activity of the synthesized compounds:

Comp code.	Mean zone of inhibition in ( mm )
	Streptococci ( G ^{+ ve})		*Pseudomonas* *aeruginisa* ( G ^{- ve})		*Staphylococcus aureus* ( G ^{+ ve})		*E. coli* ( G ^{- ve})		*Candida albicans*		*Aspergillus flavus*
	50 µg	100µg	50µg	100µg	50 µg	100µg	50µg	100µg	50µg	100µg	50 µg	100µg
BJ-1	13	18	16	18	17	19	14	18	14	17	17	19
BJ-2	18	19	14	16	18	21	17	20	16	19	14	17
BJ-3	17	21	17	20	13	20	18	20	17	19	14	16
BJ-4	14	16	15	20	14	18	17	19	16	18	18	19
BJ-5	15	18	14	16	13	18	15	17	15	18	11	17
BJ-6	17	20	17	18	19	21	16	20	17	18	13	16
BJ-7	16	18	15	17	17	19	16	19	18	20	15	17
BJ-8	18	20	16	19	18	20	16	20	18	19	18	20
Procaine penicillin	19	22	-	-	21	24	-	-	-	-	-	-
Streptomycin	-	-	18	22	-	-	19	22	-	-	-	-
Griseofulvin	-	-	-	-		-	-	-	19	24	18	22

RESULTS AND DISCUSSIONS:

From the obtained results, it is evident that most of the compounds like BJ- 2, 3, 6 and 8 show a significant activity against bacterial strains like Streptococci, Staphylococcus aureus, Pseudomonas aeruginisa and Escherichia coli. And the compounds like BJ - 1,3,4,7 and 8 shows a significant activity against fungi like Candida albicans and Aspergillus flavus and remaining compounds showed moderate activity against all bacteria and fungi tested.

CONCLUSION:

The prepared new series of Isoxazole and Pyrazole derivatives are identified by spectral data’s and form the Antimicrobial activity report the compounds shows significant to moderate properties and they also poses a wide variety of biological activities as mentioned in literature.

ACKNOWLEDGMENT:

The author and co-workers thankful to Principal Dr. D. Ranganayakulu, Department of Pharmacology and the Management and Chairperson Smt. P. Sulochanadevi, Sri Padmavathi School of Pharmacy, Tiruchanoor, Tirupati for providing facilities to successfully completing this project. Prof. Dr. B. H. M. Jayakumar Swamy, Dept. of Pharma. Chemistry, SCS College of Pharmacy, Harapanahalli for their help in spectral analysis and Biological activity so on.

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