Synthesis and Antibacterial Study of Some New Schiff's Bases of 2-Hydrazinyl-1-(1H-Imidazole-1-yl)-Ethanone
Ravi N. Patel, Urviben Yashodharabhai Patel, Ripal R. Chaudhari and Dhrubo Jyoti Sen
Department of Pharmaceutical Chemistry, Shri Sarvajanik Pharmacy College, Hemchandracharya North Gujarat University, Arvind Baug, Mehsana-384001, Gujarat, India
*Corresponding Author E-mail: dhrubosen69@yahoo.com; ripalchaudhari@yahoo.com
ABSTRACT:
Imidazole on reaction with chloroacetyl chloride afford 2-chloro-1-(1H-imidazole-1-yl)-ethanone, 1 which on treatment with hydrazine hydrate has yielded 2-hydrazinyl-1-(1H-imidazol-1-yl)-ethanone, 2. Condensation of 2 with various aromatic aldehydes afforded sustituted Schiff’s base of 2-hydrazinyl-1-(1H-imidazol-1-yl)-ethanone. The structures of all the products were characterized on the basis of their IR, Mass and 1H-NMR spectroscopic data analysis. All the synthesised products were screened for their antibacterial activity against gram-positive and gram-negative bacteria by cup-plate method.
KEYWORDS: Synthesis, Imidazole, Aromatic aldehydes, Schiff’s bases, Antibacterial activity
Imidazoles and their derivatives possess potent biological activities such as fungicidal, bactericidal, insecticidal, antibiotic, trypanocidal, larvicidal, diuretic, anticonvulsant, antiallergic, anti-inflammatory, analgesic and neuroleptic. In view of these some new substituted Schiff’s base linked with imidazole at 1 position through an acetylhydrazino bridge (Scheme-1) were synthesized by conventional synthesis. These compounds have also two nucleophilic centres, viz. hence can act as good synthons. In spite of the importance of this class of compounds not many reports have appeared on their synthesis. The products were evaluated for their antibacterial activity1-5.
The structure of the synthesized compounds were elucidated on the basis of their IR, Mass, 1H-NMR spectroscopic datas. These compounds were also screened for their antimicrobial activity.
EXPERIMENTAL:
Melting points of all the synthesised compounds were determined in open capillaries and were uncorrected. Thin layer chromatography was performed on microscopic slides (2×7.5cms) coated with Silica-Gel-Gf254 and spots were visualized under UV light and by exposure to iodine vapour. 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 Brucker Advance-II NMR 400 MHz instruments using CDCl3/DMSO-d6 as solvent and TMS (tetra methyl silane) as internal standard, chemical shifts were expressed as δ values (ppm). All the chemicals used for the synthesis of titled compounds were procured from S.D. Fine Chem., Ltd, Phenar Chemicals Ltd and Loba Chemicals. The chemicals were used without further purification6-9.
Preparation of 2-chloro-1-(1H-imidazol-1-yl)-ethanone (1):
A mixture of imidazole (6.8g, 0.1M), chloro acetyl chloride (11.2ml, 0.1M) and 25.0ml of methanol were placed into a 250ml round bottom flask and the mixture was refluxed at 30°C for 9hours. Then the mixture was cooled and recovered the solid separated out. Washed with ethanol, dried and recrystallised from absolute alcohol yielded 4.8g (70.67% w/w) of crystalline product. m.p.: 77-78°C. IR (KBr cm-1): 2270, 2242, 1785 (-N-CO-), 2879 (-C-CH2-), 767 (-C-Cl).
Preparation of 2-hydrazinyl-1-(1H-imidazol-1-yl)-ethanone (2):
A mixture of 2-chloro-1-(1H-imidazol-1-yl)-ethanone (4.0g, 0.027M), hydrazine hydrate (1.38ml, 0.027M) and 15.0ml of methanol were placed into a 100ml round bottom flask and the mixture was refluxed at 30°C for 15 hours. Then the mixture was cooled and recovered and the crystallised solid was separated out. The yield of the product was found to be 2.1g (60.0% w/w). m.p.: 181-183°C. IR (KBr cm-1): 2279, 2240, 1787 (-N-CO-), 2875 (-C-CH2), 3370, 3320 (-NHNH2).
Scheme-1: Synthesis of substituted Schiff’s bases of 2-hydrazinyl-1-(1H-imidazol-1-yl)-ethanone (3a-e):
Preparation of 2-(2-benzylidene hydrazinyl)-1-(1H-imidazol-1-yl)-ethanone (3a):
A mixture of 2-hydrazinyl-1-(1H-imidazol-1-yl)-ethanone (2) (2.0g, 0.007M), benzaldehyde (1.5ml, 0.007M) and 10.0ml of methanol were placed into a 100ml round bottom flask and the mixture was refluxed at 30°C for 6 hours. Then the mixture was cooled and recovered the yellowish solid separated out. Washed with ethanol, dried and recrystallised from absolute alcohol yielded 1.0g (50.00% w/w) of product (3a). m.p.: 240-242°C. IR (KBr cm-1): 2275, 2238, 1789 (-N-CO-), 2280 (-C-CH2), 1604 (-N=CH-). Physicochemical datas of the compounds are described in Table-1 and the characterisation data of these compounds are described in Table-2.
Antibacterial ACTIVITY:
The synthesised compounds 3a-e were screened for their in-vitro antimicrobial activity against Staphylococcus aureus, Bacillus citrus, Escherechia coli, Bacillus subtilis by measuring the zone of inhibition in mm. The antimicrobial activity was performed by cup-plate method at concentration of 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 was used as standard for antibacterial activity10-13.
Table-1: Physicochemical datas of the compounds (3a-e):
|
Cmpd. code |
Aromatic ring (Ar-) |
Molecular formulae |
Melting point (°C) |
Yield (%w/w) |
Rfa |
|
3a |
|
C12H12N4O |
240-242 |
52.00 |
0.40 |
|
3b |
|
C12H12N4O2 |
215-217 |
40.23 |
0.48 |
|
3c |
|
C12H12N4O2 |
218-220 |
50.94 |
0.50 |
|
3d |
|
C13H13N5O3 |
228-230 |
40.36 |
0.35 |
|
3e |
|
C13H13N5O3 |
227-229 |
55.29 |
0.38 |
a Mobile phase: Ethyl acetate : n-Hexane (8:2)
Table-2: Spectral data of the compounds (3a-e):
|
Compound code |
Molecular weight (g/mol) |
I.R. (cm-1, KBr) |
Mass (m/e) |
1H-NMR (DMSO-d6, ppm) |
|
3a |
228.24 |
~2275, 2238, 1789 (-N-CO-), 2880 (-C-CH2-), 1604 (-N=CH-) |
228.8 (M+) |
8.26 (s, 1H, C-5 of imidazole), 4.38 (s, 2H, CH2), 4.42 (s, 1H, -N=CH), 7.06-8.06 (m, 13H, Ar-H) |
|
3b |
244.24 |
~2276, 2233, 1785 (-N-CO-), 2881 (-C-CH2-), 1603 (-N=CH-), 1760 (-OH) |
245.1 (M+1) |
8.28 (s, 1H, C-5 of imidazole), 4.39 (s, 2H, CH2), 4.46 (s, 1H, -C=NH-), 7.06-8.02 (m, 12H, Ar-H), 1H (-OH) deuterium exchangeable |
|
3c |
244.24 |
~2273, 2238, 1789 (-N-CO-), 2883 (-C-CH2-), 1601 (-N=CH-), 1761 (-OH) |
245.1 (M+1) |
8.40 (s, 1H, C-5 of imidazole), 4.41 (s, 2H, CH2), 4.43 (s, 1H, -C=NH-), 7.08-8.02 (m, 12H, Ar-H), 1H (-OH) deuterium exchangeable |
|
3d |
274.04 |
~2271, 2239, 1787 (-N-CO-), 2880 (-C-CH2-), 1602 (-N=CH-) |
275.0 (M+1) |
8.42 (s, 1H, C-5 of imidazole), 4.38 (s, 2H, CH2), 4.45 (s, 1H, -C=NH-), 7.06-8.05 (m, 12H, Ar-H) |
|
3e |
274.04 |
~2274, 2233, 1782 (-N-CO-), 2880 (-C-CH2-), 1602 (-N=CH-) |
275.1 (M+1) |
8.38 (s, 1H, C-5 of imidazole), 4.44 (s, 2H, CH2), 4.38 (s, 1H, -C=NH-), 7.04-8.04 (m, 12H, Ar-H) |
Table-3: Antibacterial screening of the compounds (3a-e):
|
Compound code |
Zone of inhibition (mm) |
|||||||
|
S.aureus |
B.subtilis |
E.coli |
B.citrus |
|||||
|
20 (µg/ml) |
50 (µg/ml) |
20 (µg/ml) |
50 (µg/ml) |
20 (µg/ml) |
50 (µg/ml) |
20 (µg/ml) |
50 (µg/ml) |
|
|
2 |
00 |
12 |
00 |
11 |
10 |
23 |
12 |
13 |
|
3a |
13 |
14 |
10 |
10 |
12 |
23 |
12 |
14 |
|
3b |
10 |
15 |
09 |
13 |
10 |
18 |
00 |
16 |
|
3c |
10 |
16 |
08 |
13 |
10 |
16 |
00 |
18 |
|
3d |
10 |
18 |
08 |
00 |
14 |
18 |
00 |
18 |
|
3e |
12 |
19 |
10 |
00 |
14 |
18 |
00 |
18 |
|
Streptomycin |
15 |
25 |
16 |
24 |
20 |
25 |
20 |
25 |
|
DMF |
00 |
00 |
00 |
00 |
00 |
00 |
00 |
00 |
CONCLUSION:
The antibacterial screening it was observed that all the compounds exhibited activity against all the organisms employed. Compounds 2 and 3a-e were found to have good antibacterial activity at higher dilution (50µg/ml) against Staphylococcus aureus and Escherechia coli, where as the compounds 2 and 3a-e were found to have little antibacterial activity at higher dilution (50µg/ml) against Bacillus subtilis and Bacillus citrus. 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 were active towards bacteria.
ACKNOWLEDGEMENT:
The author is thankful to the Department of Pharmaceutical Chemistry and the staff members of Shri Sarvajanik Pharmacy College, Mehsana, Gujarat, India to fulfil the project work successfully.
REFERENCES:
1. Wolff M.E., Burger’s Medicinal Chemistry and Drug Discovery, 5th edition, Wiley-Interscience publication, New York (1996), 5: 537-90.
2. Srivastava S.K., Nema A., Srivastava S.D., Synthesis and antimicrobial activity of N9-[hydrazinoacetyl-(2-oxo-3-chloro-4-substituted aryl azetidine)]-carbazoles, Indian Journal of Chemistry (2008), 47B: 606-12.
3. Smith A., Antifungal activity of a benzimidazole derivative of ibuprofen, Quarterly Journal of Applied Chemistry (2008), 1(4): 948-54.
4. Shrivastav P.K., Rai K., Yadav G.S., Synthesis and local anaesthetic activity of some 2-substituted benzimidazoles, Indian Journal of Chemistry (2000), 40B: 161-62.
5. Tewari A., Mishra A., Synthesis and antiviral activities of N-substituted-2-substituted-benzimidazole derivatives, Indian Journal of Chemistry (2006), 45B: 489-93.
6. Yadav M.R., Puntambekar D.S., Sarathy K.P., Vengurlekar S, Giridhar R., QSAR analysis has been performed on a series of diarylimidazole derivatives in order to gain newer COX-2 inhibitors, Indian Journal of Chemistry (2006), 45B:475-82.
7. Bishnoi A., Srivastava K., Tripathi C.K.M., Synthesis and antimicrobial activity of 1-[p-{3´-(2´-aryl-4-oxo-1´,3´-thiazolyl)}-diphenyl/[-3´-(2´-aryl-4-oxo-1´,3´-thiazolyl)]-2-phenyl,4-cyclohexylidene-imidazol-5-ones, Indian Journal of Chemistry (2006), 45B: 2136-39.
8. Microibiological assay, Indian Pharmacopoeia (1996), 2nd edition: 100-03.
9. Kokare C.R., Pharmaceutical Microbiology Experiments and Techniques, Career Publications (2007), 2nd edition: 153-56.
10. Shah Y.R. and Sen D.J., Schiff’s bases of piperidone derivatives as fungal growth inhibitors, The Manufacturing Pharmacist (2010), 2(09): 37-44.
11. Prajapati P.M., Sen D.J. and Patel C.N., Synthesis and antifungal screening of piperidone derivative with pyrazolone substituents, Journal of Chemical and Pharmaceutical Research (2010), 2(2): 279-285.
12. Patel V.K., Sen D.J. and Patel C.N., Antimicrobial and antifungal screening of indanone acetic acid derivatives: Journal of Chemical and Pharmaceutical Research (2010), 2(2): 50-56.
13. Patel H.R., Patel P.K, Sen D.J. and Patel A.H., Growth inhibition of microorganism by bioisosterism: International Journal of Drug Development and Research (2010), 2(1): 190-196.
Received on 14.06.2010 Modified on 30.06.2010
Accepted on 08.07.2010 © AJRC All right reserved
Asian J. Research Chem. 4(1): January 2011; Page 55-57