Synthesis of some 2-methyl-5-nitroimidazole derivatives - Journal of ...

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Manisha N. Trivedi et al J. Chem. Pharm. Res., 2011, 3(1):313-319 ______________________________________________________________________________ I J 3096 (ArC-H), 2962, 2923 (C-H) 1525 (NO 2 ), 1461(CH 3 ), 1363 (S=O 2 , Asym), 1263 (C-N), 1190 (S=O 2 Sym), 3078 (ArC-H), 2955, 2918 (C-H), 1527 (NO 2 ), 1462 (CH 3 ), 1376, (S=O 2 Asym), 1263 (C-N),1175 (S=O 2 Sym) 1.52 (d, 3H, CH 3 ), 2.48 (s, 3H, CH 3 ) 4.5 (d, 2H, CH 2 ), 4.8-4.9 (m, 1H, CH) 7.4-7.65 (m, 5H, Ar- H) 1.52 (d, 3H, CH 3 ), 2.42 (s, 3H, CH 3 ) 4.45 (d, 2H, CH 2 ), 4.76-4.88 (m, 1H, CH) 7.18-7.60 (m, 5H, Ar-CH) - 339.9 (M+1) 168 Table 3 : antibacterial and antifungal activity of synthesized compounds Compound Zone of inhibition in mm at 100µg/ml S. aureus B. subtilis E. coli P. aeruginosa A. niger C. albicans A 23 23 21 22 20 21 B 23 20 23 19 21 19 C 18 17 19 18 12 14 D 22 20 23 20 20 19 E 23 22 23 21 14 15 F 24 20 22 22 13 15 G 14 16 17 18 15 17 H 16 15 13 15 14 18 I 24 22 20 21 21 20 J 23 24 21 22 20 21 Secnidazole 22 21 21 22 18 19 Ampicillin 23 23 22 21 - - Griseofulvin - - - - 23 23 * Including diameter of the well 12 mm Synthesis of 2-{[1-methyl-2-(2-methyl-5-nitro-1H-imidazol-1-yl) ethoxy] carbonyl}-3-nitrobenzoic acid (Compound H) First 3-nitrophthalic anhydride was synthesized by refluxing a mixture of 3-nirtophthalic acid (2.5 g 11.8 mmoles) and acetic anhydride (2.48 g, 24.3 mmoles) for one hour at 80˚C. The hot mixture was poured in porcelain dish, allowed to cool and crystallize. The crystals of 3- nitrophthalic anhydride were grinded in mortar with 15 ml of sodium dried ether. The product was filtered, once more washed with 15 ml of ether and dried and used for synthesis of ester in manner similar to compound G. Synthesis of 1-methyl-2-(2-methyl-5-nitro-1H-imidazol-1-yl) ethyl benzenesulfonate (Compound I) Mixture of Secnidazole (1 g, 5.4 mmoles), pyridine (1.0ml, 12.4 mmoles) and benzenesulfonyl chloride (2 gm, 11.3 mmoles) was refluxed at 60˚C for one hour. The reaction mixture was poured into 25 ml cold 2% sodium bicarbonate solution and stirred vigorously until the oil solidifies. The crude product was recrystallized from methanol. Synthesis of l-(2-methyl-5-nitro-1H imidazol-1-yl) ethyl-4-methylbenzenesulfonate (Compound J) was in similar manner. RESULTS AND DISCUSSION Ester derivatives of 1-(2-methyl-5-nitro-1H-imidazol-1-yl) propan-2-ol were synthesized and the structures of the compounds were established by means of IR, 1 H-NMR, MS and elemental analysis. All the compounds were evaluated for antibacterial and antifungal activity by cup-plate method. Compounds A, B, D, E, F, I and J have shown significant antibacterial activity. Remaining compounds have also shown moderate or weak antibacterial activity. Compounds A, 318
Manisha N. Trivedi et al J. Chem. Pharm. Res., 2011, 3(1):313-319 ______________________________________________________________________________ B, D, I and J have shown significant antifungal activity. Remaining compounds have also shown moderate or weak antifungal activity. The synthesized compounds are novel molecules and can prove as potent antimicrobial agents in future. Acknowledgements The authors are thankful to Principal, C.U.Shah College of Pharmacy, S.N.D.T womens University, Mumbai, for providing necessary facilities to carry out the work. Cipla Laboratories Ltd. Mumbai for providing gift sample of Secnidazole, Dr. Smita Kavishwar, Centaur House, Mumbai, Prof. Akamanchi K.G, Head of Pharmacy Division, UICT and Dr. Venkat Manohar, Nicholas Piramal Research Centre, Mumbai for helping with spectral analysis of compounds. REFERENCES [1] M. Bock; Arzneim. Forsch. Drug Res., 1961, 11, 587–590. [2] M. Hoffer; E. Grunberg. J.Med. Chem., 1974, 17, 1019–1020. [3] S.C. Bhatia; V.D. Shanbhag., J. Chromatogr. 1984, 3, 305, 325–334. [4] W Raether; H Hanel. Parisitol Research, 2003, 90, S19-S39. [5] N Silvia; J.Moreno; R Docampo. Enviornmental Health Perspectives., 1985, 64, 199-208 [6] BS Furniss; AJ Hannaford; PWG Smith; AR Tatchell. Vogels Textbook of Practical Organic Chemistry; fifth edition, Longman Singapore publishers, Singapore, 1989, 1241-43, 1344-60. [7] RT Morison; RN Boyd. Organic Chemistry; sixth edition, Prentice Hall of India Pvt. Ltd, New Delhi, 2000, 737-39. [8] S Patai. Chemistry of Acid Derivatives, John Wiley & Sons, New York 1979, 1, 411-36. [9] S Patai. The Chemistry of Carboxylic Acids and Esters, John Wiley & Sons, New York, 1969, 390-91,513. [10] MA Ogharuso; JF Wolfe. Synthesis of Carboxylic Acid Esters & their Derivatives, John Wiley & Sons, New York, 1991, 684. [11] Shriner; Herman; Morrill; Curtin; Fuson. The Systemic Identification of Organic Compounds, eighth edition, John Wiley & Sons, New York, 2004, 367-69. [12] Organic Synthesis, Collective 1941, 1, 394, 1923, (3), 375. [13] Ullmann’s Encyclopedia of Industrial Chemistry, Wiley VCH-01, New York, 1989,7, 657- 59, [14] Ullmann’s Encyclopedia of Industrial Chemistry, Wiley VCH-01, New York, 1989, 12, 305-26 [15] Ullmann’s Encyclopedia of Industrial Chemistry, Wiley VCH-01, New York, 1989, A3, 555-69. [16] JM Coxon. Advances in Detailed Reaction Mechanisms, Reactions of importance in synthesis, Greenwich, Jai Press, New Delhi, 1994, 3, 289. 319
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