INTRODUCTION:

Chemically the Chalcones are 1,3-diphenyl-2-propene-1-one, in which two aromatic rings are linked by a three carbon with α, β- unsaturated carbonyl system as. This is synthesized by claisen-schmidt condensation of aromatic aldehydes with acetophenone by base catalyzed or acid catalyzed followed by dehydration to yield Chalcones^1-4.These Chalcones undergo a variety of chemical reactions and are found useful in synthesis of variety of heterocyclic compounds like isoxazole and pyrazole derivatives they are obtained by reacting Chalcones a starting material with hydroxyl amine hydrochloride and hydrazine hydrate in refluxing alcohol^5-7. These synthesized compounds possess a versatile pharmacological activity like antitumor, anticancer, antitubercular, antibacterial, antifungal, antipyretic, antihelmintic, anticonvulsant, anti-inflammatory, analgesic and herbicidal properties. So the obtained compounds are evaluated for antimicrobial activity^8,9.

MATERIAL AND METHOD:

The chemicals used in this work are taken from SD fine chemicals laboratories Bengaluru, magnetic stirrers are used for starting of the reaction, and the reaction was monitored by TLC using silica gel G60 with ethyl acetate : chloroform of (6 :4) solvent system and the spots were identified by UV chamber.

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 )	% Yield	M.P. ^oc	Calculated % of Elements
Comp. Code	R¹	R²	Mol. Formula	Mol. Wt ( gms )	% Yield	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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