Synthesis and Antimicrobial Evaluation of Some New Thiazole, Thiazolidinone and Thiazoline Derivatives Starting from 1-Chloro-3,4-dihydronaphthalene-2-carboxaldehyde (original) (raw)

Abstract

New series of novel functionalized thiazoles, 1,3,4-thiadiazoles and pyrido[2,3-d][1,2,4]triazolo[4,3-a]pyrimidines containing pyrazole moiety were synthesized using 4-acetylpyrazole as a precursor. The structures of the compounds prepared were confirmed by both spectral and elemental analyses and by alternative synthetic routes. The mechanisms of the studied reactions were also discussed. Sixteen compounds were evaluated for their in vitro antimicrobial activity. The results proclaimed that some of the tested compounds exhibited moderate to significant antibacterial and antifungal activities. Compounds 11e, 11a, and 11d exhibited high antibacterial activity against Bacillus subtilis compared with reference drug (Ampicillin) while compounds 11a, 6g, 18e, 18a, 11d, 6a, 11c, 11b and 6d exhibited higher antifungal activity against Syncephalastrum racemosum than reference drug (Amphotericin B).

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References (78)

  1. m, 8H, Ar-H), 10.55 (s, br, 1H, NH);
  2. MS, m/z (%) 538 (M+2, 4), 536 (M + , 12), 489 (20), 254 (59), 212 (32), 132 (53), 91 (100). Anal. Calcd for C26H26ClN7O2S (536.05): C, 58.26; H, 4.89; N, 18.29. Found: C, 58.21; H, 4.76; N, 18.05%.
  3. -1H-pyrazole-3-carboxylate (6d): Dark red solid, (76% yield); mp 204-206 °C; IR (KBr) ν = 3440 (NH), 1716 (C=O), 1593 (C=N) cm -1 ;
  4. H-NMR (DMSO-d6): δ 1.27 (3H, t, J = 7.2, CH3CH2), 2.12 (s, 3H, CH3), 2.40 (s, 3H, CH3), 2.50 (s, 3H, CH3), 2.58 (s, 3H, CH3), 4.29 (2H, q, J = 7.2, CH3CH2), 7.25-7.49 (m, 8H, Ar-H), 10.54 (s, br, 1H, NH);
  5. MS, m/z (%) 582 (M+2, 8), 580 (M + , 9), 535 (17), 350 (12), 212 (34), 132 (62), 91 (100). Anal. Calcd for C26H26BrN7O2S (580.50): C, 53.79; H, 4.51; N, 16.89. Found: C, 53.72; H, 4.46; N, 16.75%.
  6. -1H-pyrazole-3-carboxylate (6e): Orange solid, (72% yield); mp 192-194 °C; IR (KBr) ν = 3441 (NH), 1716 (C=O), 1599 (C=N) cm -1 ;
  7. H-NMR (DMSO-d6): δ 1.27 (3H, t, J = 7.2, CH3CH2), 2.20 (s, 3H, CH3), 2.40 (s, 3H, CH3), 2.50 (s, 3H, CH3), 2.57 (s, 3H, CH3), 3.86 (s, 3H, OCH3), 4.29 (2H, q, J = 7.2, CH3CH2), 6.94-7.63 (m, 8H, Ar-H), 10.40 (s, br, 1H, NH);
  8. Ethyl 5-methyl-4-(1-(2-(4-methyl-5-(m-tolyldiazenyl)thiazol-2-yl)hydrazono)ethyl)-1-(p-tolyl)-1H- pyrazole-3-carboxylate (6f): Orange solid, (78% yield); mp 219-221 °C; IR (KBr) ν = 3435 (NH), 1718
  9. C=O), 1594 (C=N) cm -1 ;
  10. H-NMR (DMSO-d6): δ 1.25 (3H, t, J = 7.2, CH3CH2), 2.12 (s, 3H, CH3), 2.37 (s, 3H, CH3), 2.40 (s, 3H, CH3), 2.49 (s, 3H, CH3), 2.59 (s, 3H, CH3), 4.31 (2H, q, J = 7.2, CH3CH2),
  11. H, 5.60; N, 18.87%.
  12. Ethyl 5-methyl-4-(1-(2-(5-(phenyldiazenyl)-4-(thiophen-2-yl)thiazol-2-yl)hydrazono)ethyl)-1-(p- tolyl)-1H-pyrazole-3-carboxylate (6g): Red solid, (69% yield); mp 231-233 °C; IR (KBr) ν = 3427 (NH), 1714 (C=O), 1598 (C=N) cm -1 ;
  13. H-NMR (DMSO-d6): δ 1.28 (3H, t, J = 7.2, CH3CH2), 2.20 (s, 3H, CH3), 2.42 (s, 3H, CH3), 2.50 (s, 3H, CH3), 4.29 (2H, q, J = 7.2, CH3CH2), 7.21-7.57, 8.05 (m, 12H, Ar- H), 10.22 (s, br, 1H, NH);
  14. MS, m/z (%) 569 (M + , 2), 522 (9), 479 (37), 254 (41), 132 (29), 91 (100). Anal. Calcd for C29H27N7O2S2 (569.70): C, 61.14; H, 4.78; N, 17.21. Found: C, 61.07; H, 4.64; N, 17.08%. Ethyl 5-methyl-4-(1-(2-(4-phenyl-5-(phenyldiazenyl)thiazol-2-yl)hydrazono)ethyl)-1-(p-tolyl)-1H- pyrazole-3-carboxylate (6h): Dark red solid, (75% yield); mp 256-257 °C; IR (KBr) ν = 3439 (NH), 1715 (C=O), 1596 (C=N) cm -1 ;
  15. H-NMR (DMSO-d6): δ 1.29 (3H, t, J = 7.2, CH3CH2), 2.22 (s, 3H, CH3),
  16. 40 (s, 3H, CH3), 2.50 (s, 3H, CH3), 4.29 (2H, q, J = 7.2, CH3CH2), 7.31-8.29 (m, 14H, Ar-H), 10.22 (s, (100). Anal. Calcd for C18H22N4O2S2 (390.52): C, 55.36; H, 5.68; N, 14.35. Found C, 55.31; H, 5.53; N, 14.20%. General procedure for synthesis of ethyl 4-(1-((5-substituted-3-phenyl-1,3,4-thiadiazol-2(3H)- ylidene)hydrazono)ethyl)-5-methyl-1-(p-tolyl)-1H-pyrazole-3-carboxylate (11a-e). To a mixture of alkyl carbodithioate 8 (0.390 g, 1 mmol) and the appropriate hydrazonoyl halides 3 (1 mmol) in EtOH (20 mL), triethylamine (0.5 mL) was added, the mixture was stirred at room temperature for 2 h. The resulting solid was collected and crystallized from DMF to give the corresponding 1,3,4-thiadiazolines 11a-e. The products 11a-e together with their physical constants are listed below.
  17. Ethyl 4-(1-((5-acetyl-3-phenyl-1,3,4-thiadiazol-2(3H)-ylidene)hydrazono)ethyl)-5-methyl-1-(p-tolyl)- 1H-pyrazole-3-carboxylate (11a): Yellow solid, (70% yield); mp 242-244 °C; IR (KBr): ν = 1744, 1655 (2C=O), 1604 (C=N) cm -1 ;
  18. H NMR (300 MHz, DMSO-d6): δ = 1.30 (3H, t, J = 7.2, CH3CH2), 2.34 (s, 3H, CH3), 2.40 (s, 3H, CH3), 2.46 (s, 3H, CH3), 2.50 (3H, s, CH3), 4.34 (2H, q, J = 7.2, CH3CH2), 7.29- 7.44 (m, 9H, Ar-H);
  19. MS, m/z (%) 502 (M + , 21), 436 (14), 241 (61), 132 (61), 91 (100), 77 (93). Anal. Calcd for C26H26N6O3S (502.59): C, 62.13; H, 5.21; N, 16.72. Found: C, 62.07; H, 5.10; N, 16.63%. Ethyl 4-(1-((5-benzoyl-3-phenyl-1,3,4-thiadiazol-2(3H)-ylidene)hydrazono)ethyl)-5-methyl-1-(p- tolyl)
  20. -1H-pyrazole-3-carboxylate (11b): Yellow solid, (71% yield); mp 224-226 °C; IR (KBr): ν = 1744, 1652 (2C=O), 1600 (C=N) cm -1 ;
  21. H NMR (300 MHz, DMSO-d6): δ = 1.30 (3H, t, J = 7.2, CH3CH2), 2.34 (s, 3H, CH3), 2.40 (s, 3H, CH3), 2.46 (3H, s, CH3), 4.32 (2H, q, J = 7.2, CH3CH2), 7.36-7.44 (m, 14H, Ar- H);
  22. C NMR (75 MHz, DMSO-d6): δ = 11.6, 13.8, 20.6, 30.6 (CH3), 61.1 (CH2), 121.7, 122.5, 124.3, 125.4, 128.7, 129.7, 130.3, 132.7, 134.5, 135.3, 137.3, 138.9, 139.3, 139.8, 140.2, 142.5, 149.0, 153.5 (Ar-C), 162.4, 194.61 (CO). MS, m/z (%) 564 (M + , 37), 303 (38), 113 (40), 87 (100), 59 (83). Anal. Calcd for C31H28N6O3S (564.66): C, 65.94; H, 5.00; N, 14.88. Found: C, 65.74; H, 4.87; N, 14.69%. Ethyl 5-methyl-4-(1-((3-phenyl-5-(phenylcarbamoyl)-1,3,4-thiadiazol-2(3H)-ylidene)hydrazono)-
  23. -1-(p-tolyl)-1H-pyrazole-3-carboxylate (11c): Yellow solid, (73% yield); mp 278-280 °C; IR (KBr): ν = 3386 (NH), 1744, 1656 (2C=O), 1602 (C=N) cm -1 ;
  24. H NMR (300 MHz, DMSO-d6): δ = 1.30 (3H, t, J = 7.2, CH3CH2), 2.34 (s, 3H, CH3), 2.40 (s, 3H, CH3), 2.46 (3H, s, CH3), 4.34 (2H, q, J = 7.2, CH3CH2), 7.33-7.44 (m, 14H, Ar-H), 11.23 (1H, s, NH);
  25. H, 5.04; N, 16.91. Found: C, 64.19;
  26. H, 5.02; N, 16.73%.
  27. Ethyl 5-((1-(3-(ethoxycarbonyl)-5-methyl-1-(p-tolyl)-1H-pyrazol-4-yl)ethylidene)hydrazono)-4- phenyl-4,5-dihydro-1,3,4-thiadiazole-2-carboxylate (11d): Yellow solid, (71% yield); mp 236-238 °C;
  28. IR (KBr): ν = 3386 (NH), 1744, 1655 (2C=O), 1602 (C=N) cm -1 ;
  29. H NMR (300 MHz, DMSO-d6): δ = 1.19 (3H, t, J = 7.2, CH3CH2), 1.30 (3H, t, J = 7.2, CH3CH2), 2.34 (s, 3H, CH3), 2.46 (s, 3H, CH3), 2.63 (3H, s, CH3), 4.12 (2H, q, J = 7.2, CH3CH2), 4.32 (2H, q, J = 7.2, CH3CH2), 7.36-7.44 (m, 9H, Ar-H);
  30. MS, 4.93;
  31. N, 13.69. Found: C, 65.69; H, 4.88; N, 13.48%. Synthesis of ethyl 4-(3-substituted-5-oxo-1-aryl-6-(p-tolyl)-1,5-dihydropyrido[2,3-d][1,2,4]triazolo- 18a-h. To a solution of 14 (0.412 g, 1 mmol) and the appropriate hydrazonoyl chlorides 3 (1 mmol) in dioxane (20 mL) was added triethylamine (0.14 mL, 1 mmol). The reaction mixture was refluxed till all of the starting materials had disappeared (20-24 h, monitored by TLC). The solvent was evaporated and the residue was triturated with MeOH. The solid formed was collected and crystallized from the appropriate solvent to give products 18a-h. The products 18a-h together with their physical constants are listed below.
  32. Ethyl 4-(3-acetyl-5-oxo-1-phenyl-6-(p-tolyl)-1,5-dihydropyrido[2,3-d][1,2,4]triazolo[4,3-a]pyrimid- in-8-yl)-5-methyl-1-(p-tolyl)-1H-pyrazole-3-carboxylate (18a): Yellow solid, (76% yield), mp 268- 270 °C; IR (KBr) = 1705, 1678, 1620 (3C=O), 1599 (C=N) cm -1 ;
  33. H NMR (DMSO-d6) δ: 1.09 (t, J = 7.2, 3H, CH3CH2), 2.25 (s, 3H, CH3), 2.40 (s, 3H, CH3), 2.49 (s, 3H, CH3), 2.66 (s, 3H, CH3), 4.21 (q, J = 7.2, 2H, CH3CH2), 7.01-7.67 (m, 13H, Ar-H), 8.23 (s, 1H, pyridine-H);
  34. N, 15.38. Found: C, 69.61; H, 4.82; N, 15.27%.
  35. Ethyl 4-(3-acetyl-5-oxo-1,6-di-p-tolyl-1,5-dihydropyrido[2,3-d][1,2,4]triazolo[4,3-a]pyrimidin-8-yl)- 5-methyl-1-(p-tolyl)-1H-pyrazole-3-carboxylate (18b): Yellow solid, (77% yield), mp 258-260 °C; IR
  36. H NMR (DMSO-d6) δ: 1.10 (t, J = 7.2, 3H, CH3CH2), 2.21 (s, 3H, CH3), 2.29 (s, 3H, CH3), 2.41 (s, 3H, CH3), 2.49 (s, 3H, CH3), 2.64 (s, 3H, CH3),
  37. MS, m/z (%) 651 (M + ,
  38. 579 (7), 488 (2), 199 (2), 80 (3), 64 (100). Anal. Calcd for C38H33N7O4 (651.71): C, 70.03; H, 5.10; N, 15.04. Found: C, 70.01; H, 5.03; N, 14.84%.
  39. Ethyl 4-(3-acetyl-1-(4-chlorophenyl)-5-oxo-6-(p-tolyl)-1,5-dihydropyrido[2,3-d][1,2,4]triazolo[4,3- a]pyrimidin-8-yl)-5-methyl-1-(p-tolyl)-1H-pyrazole-3-carboxylate (18c): Yellow solid, (73% yield), mp 237-239 °C; IR (KBr) = 1714, 1655, 1641 (3C=O), 1591 (C=N) cm -1 ;
  40. H NMR (DMSO-d6) δ: 1.11 (t, J = 7.2, 3H, CH3CH2), 2.28 (s, 3H, CH3), 2.41 (s, 3H, CH3), 2.49 (s, 3H, CH3), 2.66 (s, 3H, CH3), 4.23 (q, J = 7.2, 2H, CH3CH2), 7.05-7.75 (m, 12H, Ar-H), 8.28 (s, 1H, pyridine-H);
  41. H NMR (DMSO-d6) δ: 1.11 (t, J = 7.2, 3H, CH3CH2), 1.33 (t, J = 7.2, 3H, CH3CH2), 2.28 (s, 3H, CH3), 2.41 (s, 3H, CH3), 2.63 (s, 3H, REFERENCES
  42. A. S. Shawali J. Adv. Res., 2014, 5, 1.
  43. A. Jamwal1, A. Javed, and V. Bhardwaj, J. Pharm. BioSci., 2013, 3, 114.
  44. K. D. Hargrave, F. K. Hess, and J. T. Oliver, J. Med. Chem., 1983, 26, 1158.
  45. W. C. Patt, H. W. Hamilton, M. D. Taylor, M. J. Ryan, D. G. Taylor, C. J. C. Connolly, A. M. Doherty, S. R. Klutchko, I. Sircar, B. A. Steinbaugh, B. L. Batley, C. A. Painchaud, S. T. Rapundalo, B. M. Michniewicz, S. C. J. Olson, J. Med. Chem., 1992, 35, 2562.
  46. R. N. Sharma, F. P. Xavier, K. K. Vasu, S. C. Chaturvedi, and S. S. Pancholi, J. Enzym. Inhib. Med. Chem., 2009, 24, 890.
  47. J. C. Jaen, L. D. Wise, B. W. Caprathe, H. Tecle, S. Bergmeier, C. C. Humblet, T. G. Heffner, L. T. Meltzner, and T. A. Pugsley, J. Med. Chem., 1990, 33, 311.
  48. K. Tsuji and H. Ishikawa, Bioorg. Med. Chem. Lett., 1994, 4, 1601; F. W. Bell, A. S. Cantrell, M. Hogberg, S. R. Jaskunas, N. G. Johansson, C. L. Jordon, M. D. Kinnick, P. Lind, J. M. Morin, R. Noreen, B. Oberg, J. A. Palkowitz, C. A. Parrish, P. Pranc, C. Sahlberg, R. J. Ternansky, R. T. Vasileff, L. Vrang, S. J. West, H. Zhang, and H. X.-X. Zhou, J. Med. Chem., 1995, 38, 4929.
  49. N. Ergenc, G. Capan, N. S. Gunay, S. Ozkirimli, M. Gungor, S. Ozbey, and E. Kendi, Arch. Pharm. Pharm. Med. Chem., 1999, 332, 343.
  50. J. S. Carter, S. Kramer, J. J. Talley, T. Penning, P. Collins, M. J. Graneto, K. Seibert, C. Koboldt, J. Masferrer, and B. Zweifel, Bioorg. Med. Chem. Lett., 1999, 9, 1171.
  51. A. Badorc, M. F. Bordes, P. de Cointet, P. Savi, A. Bernat, A. Lale, M. Petitou, J. P. Maffrand, and J. M. Herbert, J. Med. Chem., 1997, 40, 3393.
  52. J. Rudolph, H. Theis, R. Hanke, R. Endermann, L. Johannsen, and F. U. Geschke, J. Med. Chem., 2001, 44, 619.
  53. M. Fares, S. M. Abou-Seri, H. A. Abdel-Aziz, S. E. S. Abbas, M. M. Youssef, and R. A. Eladwy, Eur. J. Med. Chem., 2014, 83, 155.
  54. A. V. Astakhov and V. M. Chernyshev, Chem. Heterocycl. Compd., 2014, 50, 319.
  55. X. H. Liu, Z. H. Sun, M. Y. Yang, C. X. Tan, J. Q. Weng, Y. G. Zhang, and Y. Ma, Chem. Biol. Drug Des., 2014, 84, 342.
  56. T. A. Farghaly and H. M. E. Hassaneen, Arch. Pharm. Res., 2013, 36, 564.
  57. S. M. Gomha, Monatsh. Chem., 2009, 140, 213.
  58. S. M. Gomha and M. G. Badrey, Eur. J. Chem., 2013, 4, 180.
  59. A. O. Abdelhamid, A. A. Fahmi, and K. N. M. Halim, Synth. Commun., 2013, 43, 1101.
  60. A. Abdelazim, M. S. Ei-Gendy, and A. O. Abdelhamid, Eur. J. Chem., 2012, 3, 455.
  61. S. M. Gomha, A. S. Shawali, and A. O. Abdelhamid, Turk. J. Chem., 2014, 38, 865.
  62. S. A. Ahmad, N. A. Abdelreiheem, and A. O. Abdelhamid, Eur. Bull. Chem., 2014, 5, 334.
  63. S. A. Ahmad, O. M. Ahmad, and A. O. Abdelhamid, Eur. J. Chem., 2014, 5, 334.
  64. S. M. Gomha, K. D. Khalil, A. M. El-Zanate, and S. M. Riyadh, Heterocycles, 2013, 87, 1109.
  65. S. M. Gomha and H. M. Abdel-aziz, Heterocycles, 2015, 91, 583.
  66. A. Abdelhamid, A. S. Shawali, S. M. Gomha, and W. A. M. A. El-Enany, World J. Pharm. Pharmaceut. Sci., 2015, 4, 1695.
  67. H. A. Emam, H. F. Zohdi, and A. O. Abdelhamid, J. Res. (M), 1998, 169.
  68. R. N. Butler, Comprehensive Heterocyclic Chemistry, ed. by A. R. Katritzky, C. W. Rees, and E. F. V. Scriven, Pergamon Press: New York, NY, USA, 1996, Vol. 4, p 621.
  69. R. Huisgen, R. Grashey, M. Seidel, H. Knupfer, and R. Schmidt, Liebigs Ann. Chem., 1962, 658, 169.
  70. M. A. N. Mosselhi, Monatsh. Chem., 2002, 133, 1297.
  71. A. M. Asiri, M. E. M. Zayed, and S. W. Ng, Acta Cryst., 2011, 67, o1962.
  72. N. F. Eweiss and A. Osman, J. Heterocycl. Chem., 1980, 17, 1713.
  73. A. S. Shawali and A. Osman, Bull. Chem. Soc. Jpn., 1976, 49, 321.
  74. A. S. Shawali and A. Osman, Tetrahedron, 1971, 27, 2517.
  75. A. O. Abdelhamid and F. H. H. El-Shiatey, Phosphorus, Sulfur Silicon Relat. Elem., 1988, 39, 45.
  76. H. M. Hassaneen, A. S. Shawali, N. M. Elwan, and N. M. Abounada, Sulfur Lett., 1992, 13, 273.
  77. A. O. Abdelhamid, H. F. Zohdi, and N. M. Rateb, J. Chem. Res. (S), 1999, 184, 920.
  78. M. A. Pfaller, L. Burmeister, M. A. Ghorab, and M. G. Rinaldi, J. Clin. Microbiol., 1988, 26, 1437.