Synthesis and Anti-Bacterial Study of 6, 8- Disubstituted -3-(4-(4- Substituted Phenyl) Thiazol-2-yl)-3,4-Dihydro-2H-Benzo [E][1,3] Oxazine
Kiran J Suthar *, Harsha U Patel, Chhaganbhai N Patel and Vimal Patel
Department of Pharmaceutical and Medicinal Chemistry, Shri Sarvajanik Pharmacy College, Hemchandracharya North Gujarat University, Near Arvind Baug, Mehsana-384001, Gujarat, India.
*Corresponding Author E-mail: kiran_pharma84@yahoo.co.in
ABSTRACT
6, 8- Disubstituted -3-(4-(4- Substituted Phenyl)Thiazol-2-yl)-3,4-Dihydro-2H-Benzo[E][1,3]Oxazine have been prepared from 2-amino 4-substituted Phenyl thiazole react with substituted salicyladehyde results in 2,4- disubstituted -6-((4-(4- substituted phenyl)thiazol-2-ylimino)methyl)phenol. Then reacted with NaBH4, it give 2,4-disubstituted -6-((4-(4- substituted phenyl)thiazol-2-ylamino)methyl)phenol. Which is reacted with fomalin in chloroform yields 6, 8- Disubstituted -3-(4-(4- Substituted Phenyl)Thiazol-2-yl)-3,4-Dihydro-2H-Benzo[E][1,3]Oxazine.All the title compounds characterised on the basis of their MASS, 1H NMR spectroscopic data analysis.
KEYWORDS: Synthesis, Thiazole, salicyladehyde, Anti-Bacterial activity.
INTRODUCTION:
Some bezoxazine are reported as potent non-nucleoside HIV Type I Specific Reserve Transcriptase Inhibitors,thrombine inhibitors, antimicrobial agents.We have prepared some new 6, 8- Disubstituted -3-(4-(4- Substituted Phenyl)Thiazol-2-yl)-3,4-Dihydro-2H-Benzo[E][1,3]Oxazine (Scheme I). Various 4- substituted phenyl thiazoles exhibited antibacterial, antifungal activity at 2-position with azetidones, thiazolidinones, cinnolines and quinazolones.
Therefore our aim is to synthesize and the study the effect of various substituted pyridinone at the second position and various phenyl subtitution at the fourth position of the thiazole ring on the antibacterial activity.
The structure of the synthesized compounds were elucidated on the basis of their MASS, 1H NMR spectroscopic data. These compounds also screened for their antimicrobial activity.
EXPERIMENTAL:
Melting points of all the synthesized compounds were determined in open capillaries and are uncorrected. Thin layer chromatography was performed on microscopic slides (2×7.5cm) coated with Silica-Gel-Gf254 and spots were visualized under UV light and by exposure to iodine vapor. IR spectra of all compounds were recorded in FTIR 8400S Shimadzu Spectrophotometer using KBr. Mass spectra were obtained using 2010EV LCMS Shimadzu instrument.
The 1H-NMR was recorded on Bruker Advance-II NMR 400 MHz instruments using CDCl3 / DMSO-d6 as solvent and TMS (tetramethylsilane) as internal standard, chemical shifts were expressed as δ values (ppm).
All the chemicals use for the synthesis of titled compounds was produced from S.D. Fine Chem. Ltd, finar Chemical
Ltd, Sigma Aldrich and Loba Chemicals. The chemicals were used without further purification.
General procedure for the Preparation of 4-Phenyl thiazole 2-amine:
4- Phenyl thiazole 2-amine have prepared as per reported method.
Preparation of (E)-2-((4-phenylthiazol-2-ylimino) methyl) phenol:
A mixture of 2-amino- 4- phenyl thiazole (0.01 mole) and salicyladehyde (0.01 mole) were refluxed in ethanol (10 ml) for 2 hr. the resultant solution was cooled; the solid that separated was filtered and recrystalised from petroleum ether. , m.p .90-95,Yield 70%
Preparation of 2-((4-phenylthiazol-2-ylamino) methyl) phenol:
Sodium Borohydride (0.02 mole) was added to a solution of (E)-2-((4-phenylthiazol-2-ylimino)methyl)phenol (0.01 mole) in methanol (10 ml) and mixture was stirred for 30 min at room temperature. The solid separated, on pouring the reaction mixture in to ice cooled water, was filtered washed with water, dried and recrystalised from petroleum ether. , m.p.110-115,Yield 60%
Table- 1. Physicochemical data of the compounds.
|
Sr. no. |
R |
R1 |
R2 |
Molecular formula |
Melting point (˚C) |
% yield |
*Rf Value |
|
5a |
H |
H |
H |
C17H14N2OS |
115-118 |
50.2 |
0.35 |
|
5b |
H |
H |
Cl |
C17H13ClN2OS |
122-125 |
39.5 |
0.40 |
|
5c |
H |
Cl |
Cl |
C17H12Cl2N2OS |
127-132 |
40.8 |
0.38 |
|
5d |
Cl |
H |
H |
C17H13ClN2OS |
120-124 |
58.1 |
0.45 |
|
5e |
Cl |
H |
Cl |
C17H12Cl2N2OS |
130-132 |
53.1 |
0.50 |
|
5f |
Cl |
Cl |
Cl |
C17H11Cl3N2OS |
140-142 |
56.6 |
0.40 |
a Mobile phase Toluene: Methanol (7:3)
Table -2. Spectral data of the compounds :
|
Compd. Code |
Mol. Wt. (g/mol) |
Mass (m/e) |
1H NMR (DMSO-d6, ppm) |
|
5a |
294.37 |
295 |
4.2(s,2H,CH2O) ,5.1(s,2H,CH2N), 6.9-7.7(m,9H,Ar-H),6.1(s,1H,CH-S) |
|
5b |
328.81 |
329 |
4.2(s,2H,CH2O) ,5.1(s,2H,CH2N), 6.9-7.7(m,8H,Ar-H),6.1(s,1H,CH-S) |
|
5c |
363.26 |
365 |
4.2(s,2H,CH2O) ,5.1(s,2H,CH2N), 6.9- 7.7(m,7H,ArH),6.1(s,1H,CH-S) |
|
5d |
328.81 |
330 |
4.2(s,2H,CH2O) ,5.1(s,2H,CH2N), 6.9-7.7(m,8H,Ar-H),6.1(s,1H,CH-S) |
|
5e |
363.26 |
365 |
4.2(s,2H,CH2O) ,5.1(s,2H,CH2N), 6.9-7.7(m,7H,Ar-H),6.1(s,1H,CH-S) |
|
5f |
397 |
399 |
4.2(s,2H,CH2O) ,5.1(s,2H,CH2N), 6.9-7.7(m,6H,Ar-H),6.1(s,1H,CH-S) |
Scheme I- Synthess of 6,8- disubstituted -3-(4-(4- substituted phenyl)thiazol-2-yl)-3,4-dihydro-2H-benzo[e][1,3]oxazine
Where,5a:R=R1=R2=H,5b:R=R1=H,R2=Cl,5c:R=H,R1=R2=Cl,5d:R=Cl,R1=R2=H,5e:R=R1=Cl R2=H, 5f: R=R1=R2=Cl
Table- 3. Antibacterial data of compounds :
Zone of inhibition measured for test compounds and standard drugs: -
|
Comp. code |
Inhibition zone in mm (diameter) |
|||||
|
E.coli |
S. aureus |
B.citrus |
||||
|
20 µg/ml |
50 µg/ml |
20 µg/ml |
50 µg/ml |
20 µg/ml |
50 µg/ml |
|
|
5a |
12 |
11 |
12 |
13 |
10 |
10 |
|
5b |
12 |
15 |
14 |
16 |
11 |
14 |
|
5c |
10 |
15 |
13 |
18 |
12 |
16 |
|
5d |
10 |
16 |
11 |
14 |
11 |
14 |
|
5e |
12 |
18 |
10 |
13 |
11 |
15 |
|
5f |
10 |
19 |
10 |
16 |
9 |
15 |
|
Streptomycin |
14 |
25 |
16 |
24 |
15 |
23 |
a zone of inhibition in mm
Preparation of 3-(4-phenylthiazol-2-yl)-3,4-dihydro-2H-benzo [e][1,3] oxazine:
2-((4-phenylthiazol-2-ylamino)methyl)phenol (0.01 mole) and formalin(1 ml) were refluxed on a water bath for 5 hrs in chloroform (10 ml). The solvent was removed under vaccum and the crude solid obtained was recrystalized from petroleum ether. , m.p.115-118 .,Yield 50.2%
ANTIMICROBIAL ACTIVITY:
The synrhesized compounds were screened for their in vitro antibacterial activity against Staphylococcus aureus, B. citrus, Escheichio coli, by measuring the zone of inhibition in mm. The antibacterial activity was performed by cup plate method at concentration 20µg/ml and 50µg/ml and reported in Table-3. Nutrient agar was employed as culture medium and DMF was used as solvent control. Streptomycin used as standard for antibacterial activity.
CONCLUSION:
From the antibacterial screening it was observed that all the compounds exhibited activity against all the organisms employed. Looking at the structure activity relationship marked inhibition in bacteria was observed the compound bearing chloro substituents where as other compounds showed moderate to good activity. All the compounds showed moderate to less activity as compared to standard. As we consider all result obtained from antibacterial tests together we can say that entire compounds tested are active towards bacteria.
ACKNOWELEDGEMENT:
The authors are thankful to Department of Pharmaceutical and Medicinal Chemistry and the staff members of Shri Sarvajanik Pharmacy College, Mehsana, Gujarat, India to fulfil the project work successfully.
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Received on 02.06.2009 Modified on 06.08.2009
Accepted on 14.09.2009 İ AJRC All right reserved
Asian J. Research Chem. 2(4):Oct.-Dec. 2009 page 437-439