Int J Curr Pharm Res, Vol 9, Issue 1, 126-131Original Article
SYNTHESIS, IN VITRO ANTIMICROBIAL ACTIVITY OF SCHIFF’S BASE, AZETIDINONES AND THIAZOLIDINONES
BHAVNABEN D. MISTRY*, KISHOR R. DESAI**, NIGAM J. DESAI**
*Department of Chemistry, B. K. M. Science College, Valsad, **Department of Chemistry, Uka Tarsadia University, Bardoli-Surat
Email: bhavana_mistry11@yahoo.co.in
Received: 01 Oct 2016, Revised and Accepted: 05 Dec 2016
ABSTRACT
Objective: The objective of the present study is to synthesize 3-Chloro-4-[3-(2,4-dichloro-5-fluoro phenyl)-1H-pyrazol-4-yl]-1-(substituted) azetidin-2-one [4a-n] and 2-[3-(2,4-Dichloro-5-fluoro phenyl)-1H-pyraol-4-yl]-3-(substituted phenyl)-1,3-thiazolidin-4-one [5a-n]. The structure of all synthesized compounds were characterized by IR, 1H NMR, 13C NMR and mass spectral studies.
Methods: The titled compounds 3-Chloro-4-[3-(2,4-dichloro-5-fluoro phenyl)-1H-pyrazol-4-yl]-1-(substituted) azetidin-2-one [4a-n] and 2-[3-(2,4-Dichloro-5-fluoro phenyl)-1H-pyraol-4-yl]-3-(substituted phenyl)-1,3-thiazolidin-4-one [5a-n] were synthesized by the reaction of N-{[3-(2,4-dichloro-5-fluoro phenyl)-1H-pyraol-4-yl] methylene } substituted anilin [3a-n] with chloro acetyl chloride and thioglycolic acid respectively. Compounds N-{[3-(2,4-dichloro-5-fluoro phenyl)-1H-pyraol-4-yl] methylene} substituted aniline [3a-n] were synthesized by the reaction of 3-(2,4-dichloro-5-fluoro phenyl)-1H-pyrazol-4-carbaldehyde [2] with primary aromatic amine in alcohol. All compounds were evaluated for their antimicrobial activity.
Results: Compounds 3a,3b,3d,3j,3l,4d,4e,4j,4l,4m,5e,5g,5h,5n exhibited excellent to good antibacterial activity as compared to reference drugs.
Conclusion: In summary, N-{[3-(2,4-dichloro-5-fluoro phenyl)-1H-pyraol-4-yl] methylene } substituted anilin [3a-n], 3-Chloro-4-[3-(2,4-dichloro-5-fluoro phenyl)-1H-pyrazol-4-yl]-1-(substituted) azetidin-2-one [4a-n] and 2-[3-(2,4-Dichloro-5-fluoro phenyl)-1H-pyraol-4-yl]-3-(substituted phenyl)-1,3-thiazolidin-4-one [5a-n] derivatives have been synthesized and characterized. In vitro antimicrobial testing of the compounds was carried out by microdilution Method. Amongst the synthesised compounds, many of them had proven their antimicrobial potency which varies from good to excellent.
Keywords: Schiff’s base, 2-Azetidinone, 4-Thiazolidinone, Antimicrobial activity
© 2017 The Authors. Published by Innovare Academic Sciences Pvt Ltd. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/)
DOI: http://dx.doi.org/10.22159/ijcpr.2017v9i1.16634
INTRODUCTION
Heteroaromatic compounds have attracted considerable attention in the design of biologically active molecules and advanced organic materials. Heterocycles containing nitrogen atoms in the core structure shows a number of pharmacologically and biologically active compounds. Hence, a practical method for the preparation of such compounds is of great interest in synthetic organic chemistry. Structurally, a Schiff's base (also known as imine or azomethine) is a nitrogen analogue of an aldehyde or ketone in which the carbonyl group has been replaced by an imine or azomethine group. Schiff’s bases of pyrazole aldehydes and aromatic amines exhibit a wide range of biological activities such as antifungal [1], antibacterial [2] and antitubercular [3] etc. The biological significance of this class of compounds impelled us to continue working on the synthesis of new schiff’s bases of pyrazole derivatives.
β-Lactam containing antibacterial agents has become an integral part of chemotherapeutic arsenal available to today’s medical practitioners. Although the number of existing agents are quite extensive, but the search for better and more effective drug is still going on. Azetidinones are the very important class of compounds possessing a wide range of biological activities such as antibacterial [4], anti-inflammatory [5], antihyperlipidemic [6], anticancer [7], antimicrobial [8], antitumor [9], antitubercular [10] etc. Furthermore, thiazolidinone derivatives found to possess a wide spectrum of biological activities [11-17].
MATERIALS AND METHODS
Melting points were determined by open capillaries and are uncorrected. The progress of the reaction was checked on aluminium coated TLC plates (E. Merck) using various solvent systems as mobile phase and visualised under iodine vapour. IR-spectra (cm-1) were recorded on a Shimadzu FT-IR spectrophotometer using KBr pellet method. 1H NMR and 13C NMR spectra were recorded on a Bruker DRX-300 NMR instrument, using CDCl3 as solvent and TMS as an internal reference (chemical shifts in δ, ppm). Mass spectra were obtained on an Agilent 6520 (Q-TOF) Mass spectrometer.
Synthesis of (1E)-1-(2,4-Dichloro-5-fluorophenyl) ethanone hydrazone [1]
A mixture of 2,4-dichloro-5-fluoro acetophenone (0.01 mol) and hydrazine hydrate (0.012 mol) was refluxed in round bottom flask containing absolute alcohol (30 ml) for 2 h in the presence of few drops of acetic acid. The content of the flask was cooled to give a solid product which was filtered, washed with water, dried and recrystallized from ethanol as a yellow crystalline solid.
Synthesis of 3-(2,4-dichloro-5-fluoro phenyl)-1H-pyrazol-4-carbaldehyde [2]
To a cold solution of (1E)-1-(2,4-Dichloro-5-fluoro phenyl)ethanone hydrazone (0.015 mol) in DMF (25 ml) was added POCl3 (0.0395 mol) and resulting mixture was stirred at 55-60 °C for 5-6 h [18]. Then the mixture was cooled to room temperature and poured into ice cold water.
A saturated solution of bicarbonate was added to neutralise the solution. The precipitate so formed was filtered, washed with water, dried and recrystallized from ethanol as a yellowish white crystalline solid.
General procedure for the synthesis of N-{[3-(2, 4-dichloro-5-fluoro phenyl)-1H-pyraol-4-yl] methylene} substituted anilin [3a-n]
A mixture of 3-(2,4-dichloro-5-fluoro phenyl)-1H-pyrazol-4-carbaldehyde (0.01 mol), various primary aromatic amine (0.01 mol) and few drops of gla. Acetic acid was refluxed in methanol for six hours. Then the refluxed content was cooled to room temperature and solid separated was filtered, washed with water and recrystallized from acetone.
[3d] IR (KBr cm-1): 3389.81 (-NH), 1567.08 (C=N), 807.10 (C-Cl), 1094.22 (C-F), 1201.49 (-C-N) 1H NMR (CdCl3) δ: 6.972 (-NH), 5.996 (-CH), 7.361-7.572 (Ar-H), 7.696 (CH-Cl), 7.701 (CH-F), 9.747 (-CH=N). 13C NMR: 161.38(C1), 120.09(C2), 129.69(C3), 129.08(C4), 139.48(C5), 115.4(C6), 139.85(C7), 110.05(C8), 133.45(C9), 160.00(C10), 150.02(C11), 122.99(C12), 125.85(C13), 131.88(C14), 125.85(C15), 122.99(C16). Mass (m/z): 368.5 (M), 374.5 (M+6), 257, 230, 205, 164, 138.
[3m] IR (KBr cm-1): 1567.20 (C=N), 807.32 (C-Cl), 1095.34 (C-F), 1023.0 (-OCH3), 1202.57 (-C-N). 1H NMR (CdCl3) δ: 6.996 (-NH), 5.877 (-CH), 7.328-7.535 (Ar-H), 7.697 (CH-Cl), 7.702 (CH-F), 9.750 (-CH=N), 3.800 (-OCH3). 13C NMR: 161.45(C1), 119.99(C2), 129.78(C3), 129.59(C4), 139.45(C5), 114.44(C6), 139.95(C7), 110.05(C8), 134.55(C9), 159.97(C10), 139.45(C11), 123.25(C12), 122.25(C13), 128.08(C14), 115.50 (C15), 153.67(C16).
Mass (m/z): 364 (M), 368 (M+4), 257, 230, 200, 164, 134.
General procedure for the synthesis of 3-Chloro-4-[3-(2,4-dichloro-5-fluoro phenyl)-1H-pyrazol-4-yl]-1-(substituted) azetidin-2-one [4a-n]
Compound N-{[3-(2,4-dichloro-5-fluoro phenyl)-1H-pyrazol-4-yl] methylene}substituted anilin (0.01 mol) was dissolved in 1,4-dioxan (50 ml). To this solution chloro acetyl chloride (0.012 mol) was added drop wise with constant stirring maintaining the temperature below 10 °C and then tri ethyl amine (0.02 mol) was added to it. The mixture was stirred for 2 h. The reacrtion mixture was then refluxed for 9-10 h. The resulting solution was then poured into crushed ice and the product thus obtained was filtered, washed with water and recrystallized from ethyl acetate.
[4a] IR (KBr cm-1): 1730 (C=O), 1203 (CH-N), 760 (C-Cl), 1062 (C-F). 1H NMR (CdCl3) δ: 6.930 (-NH pyrazol), 5.958 (-CH pyrazol), 5.103 (CH-N), 3.885 (CH-Cl), 7.307-7.960 (Ar-H). 13C NMR: 161.79(C1), 120.0(C2), 131.69(C3), 129.31C4), 138.60(C5), 117.17(C6), 143.12(C7), 114.3(C8), 133.18(C9), 60.5(C10), 62.0(C11), 162.08(C12), 140.75(C13), 119.77(C14), 130.69(C15), 123.05(C16), 129.31(C17), 117.17(C18). Mass (m/z): 409 (M), 415 (M+6), 333.5, 246.5, 230, 164, 141.5.
[4j] IR (KBr cm-1): 1712 (C=O), 1205 (CH-N), 758 (C-Cl), 1070 (C-F), 2919 (-CH3). 1H NMR (CdCl3) δ: 6.931 (-NH pyrazol), 5.961 (-CH pyrazol), 5.105 (CH-N), 3.940 (CH-Cl), 7.305-8.049 (Ar-H), 2.529 (-CH3). 13C NMR: 161.59(C1), 120.0(C2), 130.69(C3), 129.5(C4), 139.97(C5), 117.29(C6), 144.15(C7), 114.39(C8), 133.19(C9), 60.05(C10), 62.0(C11), 162.0(C12), 138.0(C13), 120.48(C14), 129.31(C15), 133.38(C16), 129.31(C17), 120.48(C18). Mass (m/z): 424.5 (M), 430.5 (M+6), 333.5, 307, 259, 196, 164.
General procedure for the synthesis of 2-[3-(2,4-Dichloro-5-fluoro phenyl)-1H-pyraol-4-yl]-3-(substituted phenyl)-1,3-thiazolidin-4-one [5a-n]
A mixture of N-{[3-(2,4-dichloro-5-fluoro phenyl)-1H-pyrazol-4-yl] methylene}substituted anilin (0.01 mol), thio glycolic acid (0.01 mol) and anhydrous zinc chloride (0.01 mol) in DMF was refluxed for 11-12 h. The resulting solution was then poured into crushed ice and the product thus obtained was filtered, washed with cold water and recrystallized from methanol.
[5a] IR (KBr cm-1): 1720.20 (C=O), 1260.70 (CH-N), 760.26 (-Cl), 1066.12 (-F).
1H NMR (CdCl3) δ: 6.927 (-NH pyrazol), 5.959 (-CH pyrazol), 5.871 (CH-N), 4.01 (CH2-S), 7.324-7.704 (Ar-H). 13C NMR: 161.41(C1), 119.99(C2), 131.91(C3), 129.70(C4), 139.82(C5), 117.18(C6), 144.65(C7), 108.74(C8), 135.82(C9), 66.1(C10), 34.0(C11), 171.1(C12), 141.75(C13), 126.4(C14), 131.82(C15), 129.30(C16), 131.82(C17), 126.4(C18). Mass (m/z): 408(M), 412 (M+4), 380, 331, 245, 230, 164.
[5e] IR (KBr cm-1): 1733.35 (C=O), 1256.46 (CH-N), 766.17 (-Cl), 1063.31 (-F), 1345.04 (-NO2). 1H NMR (CdCl3) δ: 6.927 (-NH pyrazol), 5.959 (-CH pyrazol), 5.923 (CH-N), 3.975 (CH2-S), 7.323-7.703 (Ar-H). 13C NMR: 161.48(C1), 119.99(C2), 131.91(C3), 129.67(C4), 140.05(C5), 117.18(C6), 144.75(C7), 108.74(C8), 135.82(C9), 66.16(C10), 42.36(C11), 171.2(C12), 131.82(C13), 108.74(C14), 131.91(C15), 119.76(C16), 126.44(C17), 141.75(C18). Mass (m/z): 453 (M), 457 (M+4), 421, 331, 289, 230, 212, 164, 122.
Scheme
Table 1: Physical, characterization data of compound (3a-n), (4a-n) and (5a-n)
| S. No. | R | Mol. formula | Mol. Wt. gm/mol | M. P. °C | Yield % |
| 3a | H | C16H10N3Cl2F | 334 | 120 | 68 |
| 3b | 2-Cl | C16H9N3Cl3F | 368.5 | 140 | 64 |
| 3c | 3-Cl | C16H9N3Cl3F | 368.5 | 120 | 62 |
| 3d | 4-Cl | C16H9N3Cl3F | 368.5 | 156 | 65 |
| 3e | 2-NO2 | C16H9O2N4Cl2F | 379 | 152 | 54 |
| 3f | 3-NO2 | C16H9O2N4Cl2F | 379 | 140 | 50 |
| 3g | 4-NO2 | C16H9O2N4Cl2F | 379 | 148 | 56 |
| 3h | 2-CH3 | C17H12N3Cl2F | 348 | 180 | 0 |
| 3i | 3-CH3 | C17H12N3Cl2F | 348 | 182 | 58 |
| 3j | 4-CH3 | C17H12N3Cl2F | 348 | 180 | 60 |
| 3k | 2-OCH3 | C17H12ON3Cl2F | 364 | 210 | 66 |
| 3l | 3-OCH3 | C17H12ON3Cl2F | 364 | 190 | 60 |
| 3m | 4-OCH3 | C17H12ON3Cl2F | 364 | 204 | 64 |
| 3n | C10H7 (naphthyl) | C20H12N3Cl2F | 384 | 180 | 56 |
| 4a | H | C18H11ON3Cl3F | 410.5 | 130 | 58 |
| 4b | 2-Cl | C18H10ON3Cl4F | 445 | 170 | 54 |
| 4c | 3-Cl | C18H10ON3Cl4F | 445 | 186 | 51 |
| 4d | 4-Cl | C18H10ON3Cl4F | 445 | 200 | 5 |
| 4e | 2-NO2 | C18H10O3N4Cl3F | 455.5 | 160 | 47 |
| 4f | 3-NO2 | C18H10O3N4Cl3F | 455.5 | 120 | 46 |
| 4g | 4-NO2 | C18H10O3N4Cl3F | 455.5 | 166 | 49 |
| 4h | 2-CH3 | C19H13ON3Cl3F | 424.5 | 196 | 54 |
| 4i | 3-CH3 | C19H13ON3Cl3F | 424.5 | 132 | 42 |
| 4j | 4-CH3 | C19H13ON3Cl3F | 424.5 | 100 | 51 |
| 4k | 2-OCH3 | C19H13O2N3Cl3F | 440.5 | 220 | 44 |
| 4l | 3-OCH3 | C19H13O2N3Cl3F | 440.5 | 202 | 40 |
| 4m | 4-OCH3 | C19H13O2N3Cl3F | 440.5 | 176 | 42 |
| 4n | C10H7 (naphthyl) | C22H13ON3Cl3F | 460.5 | 190 | 40 |
| 5a | H | C18H12ON3Cl2FS | 408 | 127 | 56 |
| 5b | 2-Cl | C18H11ON3Cl3FS | 442.5 | 152 | 48 |
| 5c | 3-Cl | C18H11ON3Cl3FS | 442.5 | 173 | 47 |
| 5d | 4-Cl | C18H11ON3Cl3FS | 442.5 | 200 | 50 |
| 5e | 2-NO2 | C18H11O3N4Cl2FS | 453 | 160 | 51 |
| 5f | 3-NO2 | C18H11O3N4Cl2FS | 453 | 120 | 48 |
| 5g | 4-NO2 | C18H11O3N4Cl2FS | 453 | 186 | 50 |
| 5h | 2-CH3 | C19H14ON3Cl2FS | 422 | 120 | 58 |
| 5i | 3-CH3 | C19H14ON3Cl2FS | 422 | 142 | 56 |
| 5j | 4-CH3 | C19H14ON3Cl2FS | 422 | 168 | 60 |
| 5k | 2-OCH3 | C19H14O2N3Cl2FS | 438 | 260 | 52 |
| 5l | 3-OCH3 | C19H14O2N3Cl2FS | 438 | 210 | 50 |
| 5m | 4-OCH3 | C19H14O2N3Cl2FS | 438 | 224 | 52 |
| 5n | C10H7 (naphthyl) | C22H14ON3Cl2FS | 458 | 230 | 42 |
Antimicrobial activity
Following common standard strains were used for screening of antibacterial and antifungal activities: E. Coli (MTCC 442), P. Aeruginosa (MTCC 441), S. Aureus (MTCC 96), S. Pyogenus (MTCC 443), C. Albicans (MTCC 227), A. Niger (MTCC 282), A. Clavatus (MTCC 1323). The strains were procured from Institute of Microbial Technology, Chandigarh. DMSO was used as diluents/vehicle to get desired concentration of drugs to test upon standard bacterial strains. Each synthesised drug was diluted for obtaining 2000 microgram/ml concentration, as a stock solution. In primary screening 1000 microgram/ml, 500 microgram/ml, and 250 microgram/ml concentrations of the synthesised drugs were taken. The actively synthesised drugs found in this primary screening were further tested in the second set of dilution against all microorganisms. The drugs found active in primary screening were similarly diluted to obtain 200 microgram/ml, 100 microgram/ml, 50 microgram/ml, 25 microgram/ml, 12.5 microgram/ml and 6.250 microgram/ml concentrations. The highest dilution showing at least 99 % inhibition zone is taken as MIC. The result of this is much affected by the size of the inoculums. Gentamycin, Ampicillin, Chloramphenicol, Ciprofloxacin, Norfloxacin, Nystatin and Griseofulvin were used as a standard. The Comparative activities of the newly synthesised compounds and the control antibiotics on bacterial and fungal strains respectively were summarised in table 2 and table 3.
Excellent to good activity was observed in compounds 4d (against E. Coli, P. Aeruginosa, S. Aureus, S. Pyogenus), compounds 3g, 4e, 5g, 5n (against E. Coli, S. Aureus, S. Pyogenus), compounds 3a, 3b, 3j, 3l, 4j, 4l, 4m, 5e, 5h (against E. Coli, S. Aureus) as well as compounds 3a, 3c, 3f, 3g, 3h, 3j, 3k, 3l, 4c, 4e, 4f, 4g, 4h, 4k, 4l, 4m, 5b, 5e, 5f, 5g, 5i, 5j, 5l, 5m (against C. Albicans). The remaining compounds were found effective at a much higher concentration as compared to the standard drugs.
Table 2: Antibacterial activity of compounds 3a-n, 4a-n and 5a-n
| Code | E. Coli | P. Aeruginosa | S. Aureus | S. Pyogenus |
| No. | MTCC 442 | MTCC 441 | MTCC 96 | MTCC 443 |
| 3a | 100 | 200 | 250 | 125 |
| 3b | 62.5 | 100 | 125 | 200 |
| 3c | 200 | 125 | 250 | 62.5 |
| 3d | 250 | 200 | 200 | 200 |
| 3e | 200 | 125 | 250 | 125 |
| 3f | 125 | 125 | 250 | 62.5 |
| 3g | 62.5 | 200 | 100 | 100 |
| 3h | 200 | 250 | 250 | 250 |
| 3i | 250 | 250 | 500 | 100 |
| 3j | 100 | 200 | 250 | 125 |
| 3k | 250 | 200 | 100 | 125 |
| 3l | 100 | 125 | 100 | 250 |
| 3m | 62.5 | 250 | 500 | 500 |
| 3n | 200 | 125 | 250 | 500 |
| 4a | 200 | 250 | 500 | 500 |
| 4b | 100 | 200 | 500 | 250 |
| 4c | 125 | 100 | 250 | 500 |
| 4d | 62.5 | 50 | 100 | 100 |
| 4e | 100 | 125 | 250 | 100 |
| 4f | 250 | 100 | 200 | 200 |
| 4g | 500 | 500 | 100 | 200 |
| 4h | 250 | 250 | 500 | 500 |
| 4i | 200 | 200 | 200 | 250 |
| 4j | 62.5 | 100 | 200 | 250 |
| 4k | 200 | 250 | 250 | 250 |
| 4l | 100 | 62.5 | 62.5 | 125 |
| 4m | 62.5 | 100 | 200 | 200 |
| 4n | 125 | 100 | 250 | 250 |
| 5a | 200 | 125 | 100 | 125 |
| 5b | 125 | 62.5 | 100 | 100 |
| 5c | 200 | 62.5 | 100 | 250 |
| 5d | 200 | 250 | 250 | 250 |
| 5e | 100 | 125 | 250 | 500 |
| 5f | 200 | 250 | 200 | 250 |
| 5g | 62.5 | 100 | 100 | 62.5 |
| 5h | 62.5 | 125 | 250 | 250 |
| 5i | 250 | 250 | 250 | 500 |
| 5j | 100 | 125 | 500 | 500 |
| 5k | 250 | 250 | 125 | 100 |
| 5l | 250 | 500 | 500 | 500 |
| 5m | 500 | 250 | 500 | 500 |
| 5n | 100 | 125 | 250 | 100 |
| Ampicillin | 100 | -- | 250 | 100 |
| Chloramphenicol | 50 | 50 | 50 | 50 |
| Ciprofloxacin | 25 | 25 | 50 | 50 |
| Norfloxacin | 10 | 10 | 10 | 10 |
Table 3: Antifungal activity of compounds 3a-n, 4a-n and 5a-n
| Code | C. albicans | A. niger | A. clavatus |
| No. | MTCC 227 | MTCC 282 | MTCC 1323 |
| 3a | 500 | 250 | 250 |
| 3b | 1000 | 1000 | >1000 |
| 3c | 250 | 1000 | 1000 |
| 3d | >1000 | 1000 | 1000 |
| 3e | >1000 | 1000 | 1000 |
| 3f | 500 | 500 | 500 |
| 3g | 500 | 500 | 1000 |
| 3h | 250 | 500 | 500 |
| 3i | >1000 | 1000 | 1000 |
| 3j | 100 | >1000 | >1000 |
| 3k | 500 | 1000 | 1000 |
| 3l | 500 | >1000 | >1000 |
| 3m | 1000 | 500 | 500 |
| 3n | >1000 | 500 | 500 |
| 4a | >1000 | 500 | 500 |
| 4b | >1000 | 500 | 500 |
| 4c | 500 | 1000 | 1000 |
| 4d | 1000 | 1000 | 500 |
| 4e | 500 | >1000 | >1000 |
| 4f | 500 | 200 | 500 |
| 4g | 250 | 1000 | 1000 |
| 4h | 500 | 1000 | 1000 |
| 4i | 1000 | 500 | 500 |
| 4j | 1000 | 1000 | 1000 |
| 4k | 250 | 1000 | >1000 |
| 4l | 500 | 500 | 1000 |
| 4m | 500 | 250 | 500 |
| 4n | 1000 | >1000 | >1000 |
| 5a | 1000 | 500 | 500 |
| 5b | 500 | 500 | 500 |
| 5c | 1000 | 1000 | 1000 |
| 5d | >1000 | >1000 | >1000 |
| 5e | 500 | 500 | 500 |
| 5f | 250 | 500 | 500 |
| 5g | 500 | >1000 | >1000 |
| 5h | 1000 | 500 | >1000 |
| 5i | 250 | >1000 | >1000 |
| 5j | 250 | 1000 | >1000 |
| 5k | 1000 | >1000 | >1000 |
| 5l | 500 | 500 | 500 |
| 5m | 200 | 500 | 1000 |
| 5n | >1000 | 500 | 500 |
| Nystatin | 100 | 100 | 100 |
| Greseofulvin | 500 | 100 | 100 |
RESULTS AND DISCUSSION
The compounds were synthesised as per scheme
Compound (1E)-1-(2,4-Dichloro-5-fluorophenyl) ethanone hydrazone 1 were synthesized from 1-(2,4-dichloro-5-fluorophenyl) ethanone, which upon reaction with DMF/POCl3 yields 3-(2,4-dichloro-5-fluoro phenyl)-1H-pyrazol-4-carbaldehyde 2. Compounds N-{[3-(2,4-dichloro-5-fluoro phenyl)-1H-pyraol-4-yl] methylene } substituted anilin [3a-n] were synthesized from 3-(2,4-dichloro-5-fluoro phenyl)-1H-pyrazol-4-carbaldehyde 2 and various aromatic amine, which upon cyclization with chloro acetyl chloride and thioglycolic acid yields 3-Chloro-4-[3-(2,4-dichloro-5-fluoro phenyl)-1H-pyrazol-4-yl]-1-(substituted) azetidin -2-one [4a-n] and 2-[3-(2,4-Dichloro-5-fluoro phenyl)-1H-pyraol-4-yl]-3-(substituted phenyl)-1,3-thiazolidin-4-one [5a-n] respectively. The proposed structures of all the synthesised compounds were well supported by IR, 1H NMR, 13C NMR and mass spectral data. The formation of compounds 3a-n was confirmed by the appearance of singlet signal at δ 9.747-9.750 for CH=N system. The 1H NMR spectrum also displayed signals at δ 5.103-5.105 for CH-N of azetidine ring and at δ 4.01-3.975 for CH2-S of thiazolidinone ring system respectively. Aromatic protons were observed in the usual region as multiplet between δ 7.328-7.535, δ 7.305-8.049, δ 7.323-7.703.
CONCLUSION
In summary, N-{[3-(2,4-dichloro-5-fluoro phenyl)-1H-pyraol-4-yl] methylene } substituted anilin [3a-n], 3-Chloro-4-[3-(2,4-dichloro-5-fluoro phenyl)-1H-pyrazol-4-yl]-1-(substituted) azetidin-2-one [4a-n] and 2-[3-(2,4-Dichloro-5-fluoro phenyl)-1H-pyraol-4-yl]-3-(substituted phenyl)-1,3-thiazolidin-4-one [5a-n] derivatives have been synthesized and characterized. In vitro antimicrobial testing of the compounds was carried out by microdilution Method. Amongst the synthesised compounds, many of them had proven their antimicrobial potency which varies from good to excellent. Excellent to good activity was observed in compounds 4d (against E. Coli, P. Aeruginosa, S. Aureus, S. Pyogenus), compounds 3g, 4e, 5g, 5n (against E. Coli, S. Aureus, S. Pyogenus), compounds 3a, 3b, 3j, 3l, 4j, 4l, 4m, 5e, 5h (against E. Coli, S. Aureus) as well as compounds 3a, 3c, 3f, 3g, 3h, 3j, 3k, 3l, 4c, 4e, 4f, 4g, 4h, 4k, 4l, 4m, 5b, 5e, 5f, 5g, 5i, 5j, 5l, 5m (against C. Albicans). The remaining compounds were found effective at a much higher concentration as compared to the standard drugs.
ACKNOWLEDGEMENT
The services of SAIF, CDRI, Lucknow and Micro care Lab Surat is acknowledged for spectral analysis and antimicrobial testing respectively.
CONFLICT OF INTERESTS
Declared none
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How to cite this article
- Bhavnaben D Mistry, Kishor R Desai, Nigam J Desai. Synthesis, in vitro antimicrobial activity of schiff’s base, azetidinones and thiazolidinones. Int J Curr Pharm Res 2017;9(1):126-131.