Synthesis and Evaluation of Some New Phenyl Thiazole Derivatives for Their Anti-Microbial Activities

SR Pattan¹*, RL Hullolikar, JS Pattan^2, NS Dighe¹, mb hole¹, sh kale¹ and SB Bhaar³

¹Department of Medicinal Chemistry, Pravara Rural College Of Pharmacy, Pravaranagar, Loni 413713, India

²Department of Biotechnology ,P V P Science College, Pravaranagar, Loni 413713, India

³Department of Pharmacology, Pravara Rural College Of Pharmacy, Pravaranagar, Loni 413713, India

*Corresponding Author E-mail: shashipattan@yahoo.com

ABSTRACT

Fifteen novel derivatives of phenyl thiazole derivatives were synthesized. The synthesized compounds were tested for their preliminary tests, physical constants, TLC, solubility, etc. the structures of the final compounds were confirmed by IR, ¹H-NMR Spectra and CHN analysis. The proposed compounds were screened for their antimicrobial, antifungal, activities with the standard drugs.

INTRODUCTION:

The need of new anti-microbial agents is justified because more microorganisms are being resistance to the present drugs available in the market. Word wide researchers are trying to synthesize new drugs with better pharmacokinetic and dynamic properties with less adverse effects. The literature survey suggests that the aryl thiazole have proved to be good bioactive molecules. They have shown diverse biological activities like anti-bacterial, anti-fungal, anti inflammatory, anti-tubercular, anticonvulsant, anti-HIV, cardiac stimulant, and diuretic and anticancer etc.therefore in view of above facts it was thought of interest to synthesize some phenyl thiazole derivatives. The structures of the final compounds were confirmed by IR, ¹H-NMR Spectra and CHN analysis. The proposed compounds were screened for their antimicrobial, antifungal activities with the standard drugs in the well-equipped microbiology lab by using standard procedure.

MATERIAL AND METHODS:

Antifungal Activity: ^3-4

The compounds were tested in-vitro for their antifungal activity against Candida albicans (ATCC 10231) and Aspergillus niger (ATCC 16)

Method: Cup-Plate agar diffusion method using Sabouraud-dextrose agar using C.albicans and A.niger.

EXPERIMENTAL:

Synthesis of 2-amino-4-substitueted phenyl thiazole^5,8(I):

A mixture consisting of 0.1mole of ketone, 0.2mole of thiourea and 0.1 mole of Iodine was heated overnight on the steam bath. This crude reaction mixture was cooled and extracted with ether to remove unreacted ketone and iodine. This residue was then dissolved in boiling water and filtered to remove sulphur. Then the solution was cooled some what and made basic with ammonium hydroxide. The amino thiazole which separated was recrystallized from water –alcohol. Melting point 125-135^oC.

Synthesis of (Z)-4-((2, 4-Dioxothiazolidin-5-ylidene) methyl)-N-(4-substituted phenylthiazol-2-yl) benzenesulfonamides⁵ (T_1-T₄):                                                                                               

0.1mole of substituted aryl thiazole and 0.1 mole of 4’-chlorosuplhonyl benzylidine-2, 4-thiazolidinedione were added to a mixture of 4 ml of dry pyridine and 20 ml of acetic anhydride. The mixture was refluxed for 2 hour. The reaction mixture was then poured into 20 ml of ice water and solid obtained was filtered and purified by recrystallization from ethanol.

Table No-1 Analytical and Physicochemical data of the synthesized compounds (T₁-T₁₅)

Comp.	Mol. Formula	Mol. Wt.	m.p. ° C	Yield   %	Elemental analyses Calcd. (Found)			LogP	CLogP	CMR
					C	H	N
T1	C19H13N3O4S3	443.51	185	78	51.47 (51.45)	2.97 (2.95)	9.50                             (9.47)	3.7	2.37	11.7
T2	C19H13N3O5S3	459.59	234	81	49.70	2.88	9.17	5.7	1.9	11.9
T3	C19H12 ClN3O4S3	477.96	260	66	47.80	2.55	8..81	4.2	3.09	12.2
T4	C20H15N3O5S3	473.54	241	55	50.75 (50.73)	3.21 (3.19)	8.90 (8.87)	3.1	1.3	12.3
T5	C35H35N3OS	387.14	90	84	71.31 (71.29)	5.48 (5.46)	10.87 (10.84)	6.0	5.9	11.5
T6	C16H19N3OS	301.40	153	71	63.80	6.38	13.97	3.3	3.8	8.6
T7	C23H19N3O2S	401.80	74	67	68.84 (68.81)	4.80 (4.77)	10.50 (10.47)	5.6	5.4	11.6
T8	C15H19N3O2S	305.39	105	80	59.22	5.98	13.83	-	1.54	8.1
T9	C17 H21N3O2S	331.43	225	83	61.65 (61.61)	6.42 (6.39)	12.70 (12.68)	2.7	2.8	9.2
T10	C16H21N3O2S	319.42	233	75	60.19	6.65	13.19	-	0.48	8.56
T11	C24H18N3O2S	415.50	140	73	69.39	5.12	10.14	-	1.9	12.0
T12	C23H18ClN3OS	419.92	95	68	65.80 (65.78)	4.35 (4.32)	10.06 (10.01)	-	3.7	11.94
T13	C16H18ClN3OS	335.85	104	72	57.25	5.44	12.54	3.8	4.5	9.1
T14	C15H19N3OS	289.39	128	86	62.50	6.32	14.60	-	2.0	8.0
T15	C16H19N3O2S	377.40	83	54	60.58	6.05	13.28	2.9	3.37	8.7

The combustion analysis of compounds synthesized is within the limits of permissible errors.

SCHEME- I:

Compounds	R
T1	-H
T2	-OH
T3	-Cl
T4	-OCH3

Compounds	R	R1
T5	-H
T6	-H
T7	-OH
T8	-OH
T9	-CH3O
T10	-CH3O
T11	-CH3O
T12	-Cl
T13	-Cl
T14	H
T15	-OH

Synthesis of 2 – substituted - N - (4 -Substituted - phenyl thiazol – 2 yl) Acetamides (T₅-T₁₅)⁵

A mixture of 0.01 mole of each 2-chloro-N- ( 4- substituted phenyl thiazol-2-yl) acetamides (II) were taken in  dry 250 ml round bottom flask separately to this distilled alcohol is added as solvent and to this different secondary amines were added  in 0.01 mole concentrations and refluxed for 2 hour after reflux add  reaction mixture to crushed ice precipitation formed is filtered and recrystallized by distilled alcohol and product was dried in vacuum dessicator,  melting points and percentage yields were reported in Table.

RESULT AND DISCUSSION:

A new series of 2-substitued phenyl thiazoles were sunthesized.The structure of these compounds were confirmed by IR, ¹H-NMR spectra and elemental analysis. Compounds were screened for antimicrobial activities by standard procedure.

SL. No.	Compd.	Zone of inhibition at 100 mcg/mL (in mm.)
		E.coli	S. aureus	A. niger	C. albicans
1	T1	21	22	23	24
2	T2	16	15	18	19
3	T3	22	19	18	20
4	T4	15	16	22	23
5	T5	14	16	23	22
6	T6	23	24	26	27
7	T7	21	17	17	18
8	T8	16	18	21	22
9	T9	24	25	25	27
10.	T10	14	15	16	18
11.	T11	21	22	18	19
12.	T12	15	17	16	19
13.	T13	24	25	28	29
14.	T14	16	15	16	19
15.	T15	24	23	25	24
Std	Ciprofloxacin	20	22	--	--
Std	Griseofulvin	--	--	24	24

Table No. 2 Antibacterial and Antifungal activity of the synthesized compounds (T₁-T₁₅)

compounds t₁, t_3, t₆, t₇, t₉, t₁₁, t₁₃, and t₁₅, have shown promising antibacterial activities. compounds t₁, t_4, t₅, t₆, t₈, t₉, T13 and t₁₅ have shown excellent antifungal activities. With the suitable molecular modification these compounds may prove as potential antimicrobial agents in future.

Table no: 3 Infra Red / ¹H-NMR spectral study of the synthesized compounds. (T₁-T₁₅)

Compd. Code	IR Bands  (cm^-1)	Types of Vibrations	d Values in ppm	No. Of Protons
T1	3167,3023 1697,3065 1580,716 820,788	-N-H str.-C-H Ar. str. -C=O str. -C=Cstr.-C=N str. -C-S str. -C-H def.	11.96 7.41-7.79 7.28,7.98	2H of NH 9 H m Ar CH 1H Ar of thiazole 1H of HC=C
T2	3166,2995 1697,3062 1580,693 799,840	-N-H str.-C-H Ar. str. -C=O str. -C=Cstr.-C=N str. -C-S str. -C-H def.
T3	3173,2998 1700,3069 1581,711 733,710	-N-H str.-C-H Ar.str. -C=O str. -C=Cstr.-C=N str. -C-S str.-C-H def
T4	1177,3169 2924,1696 3034,1581 690	-C-O-N-H str. -C-H Ar.str. -C=O str. -C=Cstr. -C=N str.-C-S str.	12.0, 7.94 7.01-7.69 7.35,3.82	2H of NH 8H m Ar CH 1H of thiazole 3H of  -OCH3 1H of HC=C
T5	3159, 3114 1597,3041 1533,1315 716,746,773	-N-H str.-C-H Ar.str. -C=O str. -C=Cstr -C=N str. -C-N str.-C-S str -C-H def	6.68-7.34 7.25,3.2	15H m Ar CH 1H of thiazole 3H of  CH2
T6	3255,3114 1599,1533 3072	-N-H str.-C-H Ar.str. -C=O str. -C=N str.-C-N` str
T7	3381,3127 3040,1736 3084,1596 746	O-H str-N-H str -C-H Ar. str. -C=O str. -C-N str. -C=N str.-C-S str.	9.23,3.28 2.15, 7.68 6.42-7.59	1H of Ar-OH 2H of CH2 H of NH 14 H m Ar CH H of thiazole
T8	3273,3135 2861,1589 1562,1389 732	O-H str-N-H str. -C-H Ar. str. -C=O str. -C=Nstr. -C-N str.-C-S str.
T9	3117,2962 3000,1607 2924,1179 1537, 1246	-N-H str.-C-H Ar. str. -C=O str. -C-H. str of Alkyl -C-O str.-C=N str. -C-N str.	3.80-3.86 7.05-7.55 7.61,3.34 1.25-2.54	3H of CH3 4H of Ar CH 1H of thiazole 2H of CH2 10H of piperidine
T10	1179,3116 2998,2963 1606,1534 738,2838	-C-O str-N-H str. -C-H Ar.str. -C=O str. -C=N str. -C-S str.-C-H Alk. str.
T11	3118,2994 2962,1598 2839,1179 1537,787,745	-N-H str.-C-H Ar. str. -C=O str. -C-H Alk.str. -C-O str. -C=N str.-C-H  str.
T12	827,2972 2923,1595 3113,2852 1536,1317	-C-Cl str-C-H Ar. str. -C=O str.-N-H str.-C-H Alk str.-C=N str.-C-N str.	6.83-7.91 7.71 3.26-3.86
T13	827,2922 1591,2852 3115,1340	-C-Cl,-C-H Ar. str. -C=O str. -C-H Alk.str.-N-H str. -C-N str.
T14	3112,2955 2921,1600 2851,1339 716,772	-N-H str.-C-H Ar. str. -C=O str. -C-H Alk.str. -C-N str. -C-H def.
T15	3378,3126 2923,1602 2854,1536 1341	-O-H str.-N-H str. -C-H Ar. str. -C=O str. -C-H Alk.str.-C=N str.-C-N str.

ACKNOWLEDGEMENTS:

Authors wish to thank Honorable Shri. Radhakrishna Vikhe Patil, Minister for Education, Law and Justice Govt. of Maharashtra for his constant encouragement and support.  Sincere thanks to Dr. S R Walunj, Secretary, Pravara Rural Education Society, Loni  for providing all necessary facilities.

REFRENCES:

1. Indian pharmacopoeia. New Delhi: Govt. of India, 1996; 2: A: 104-08.

2. Ananthnarayan R, Paniker J. Text book of microbiology. 5^th Edition, Madras: orient Longman, 1997; 36-44.

3. A.L. Barry, The antimicrobial susceptibility test: principle and practices, edited by IIIus Leu and Febiger (Philadelphia, Pa. USA), 180; Biol. Abstr., 64 (1976), 25783.

4. Kobayashi Gs, Medofff Gm. Antifungal agents: recent developments. Ann.Rev. Microbiology 1977; 31: 291-08.

5. Xiao H, Xiao ZW, Biao Jiang, Synthesis and biological activities of Bis(3-indolyl) thiazoles, analogues of marine Bis(indole) alkaloid Nortopsentins. Bio.Org.Med.Chem.Letters, 1999;9:569-572

6. Furniss BS, Hannaford AJ, Smith PWG, Patchel AR. Vogel’s Textbook of Practical Organic Chemistry. 5^th edition, Pearson education (Singapore) Pvt. Ltd.; 1996:1269.

7. Yadhav L, Rai V K, Yadhav S. Multicomponent solvent–free cyclocondensation/glycosylation strategy for thiazolo-s-triazine N-nucleosides. Letters in organic chemistry. Bentham science publishers Ltd; 4(1) 47-50.

8. Shoeb, Korekar HA, Tamman MI, Pharmazie GH. Synthesis of 4-formyl phenoxy acetic acid from substituted aryl aldehydes. Chem.Abstratcs. 1978; 33: 200-215.

Received on  02.08.2009        Modified on 12.08.2009

Accepted on 16.08.2009       © AJRC All right reserved

Asian J. Research Chem.  2(3): July-Sept., 2009, page 292-296