Journal of the Korean Chemical Society (대한화학회지)

Korean Chemical Society (대한화학회)
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A Convenient Synthesis of New 2-Phenylthieno[3,2-e][1,2,4]triazolo[1,5-c]pyrimidine Derivatives by Dimroth Rearrangement

Dimroth 재배열을 이용한 새로운 2-Phenylthieno[3,2-e][1,2,4]triazolo[1,5-c]pyrimidine 유도체의 편리한 합성

  • Received : 2010.02.27
  • Accepted : 2010.04.08
  • Published : 2010.06.20
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Abstract

Keywords

EXPERIMENTAL

All products were characterized by IR, 1H NMR, MS and elemental analysis. Melting points were measured by using the capillary tubes on Büchi apparatus and are uncorrected. Each compound of the reactions was checked on thin-layer chromatography of Merck Kieselgel 60F254 and purified by column chromatography using Merck silica gel (70 - 230 mesh). IR spectra were recorded on the FT-IR Brucker Tensor 27. The 1H NMR spectra were recorded on Bruker DRX-300 FT-NMR spectrometer (300 MHz) with Me4Si as internal standard and chemical shifts are given in ppm (δ). Electron ionization mass spectra were recorded on a HP 59580 B spectrometer. Elemental analyses were performed on a Carlo Erba 1106 elemental analyzer.

General procedure for the preparation of 2-phenylthieno[3,2-e][1,2,4]triazolo[1,5-c]pyrimidine derivatives (5). To a solution of each 3-phenylthieno[3,2-e][1,2,4]triazolo[4,3-c] pyrimidine 4 (1 mmol) in ethanol (30 mL) was added sodium acetate (0.164 g, 2 mmol) and the mixture was refluxed for 5 h and cooled. The precipitated solid was filtered, washed with water, dried and finally crystallized from ethanol to give the respective 2-phenylthieno[3,2-e][1,2,4]triazolo[1,5-c]pyrimidine 5.

2-Phenylthieno[3,2-e][1,2,4]triazolo[1,5-c]pyrimidine (5a). Yield 76%; mp 184 - 186 ℃; IR (KBr): 3062, 1631 cm-1; 1H NMR (CDCl3): δ 9.27 (s, 1H, pyrimidine-H), 8.37-8.33 (m, 2H, phenyl, H-2 and H-6), 7.88 (d, J = 5.9 Hz, 1H, thiophene), 7.70 (d, J = 5.9 Hz, thiophene), 7.56-7.52 (m, 3H, phenyl, H-3, H-4 and H-5); MS: (m/z) 252 (M+, 100), 149 (10), 134 (17), 118 (20), 95 (10), 77 (8). Anal. Calcd. for C13H8N4S: C, 61.89; H, 3.20; N, 22.21. Found: C, 61.71; H, 3.32; N, 22.05.

2-(4-Chlorophenyl)thieno[3,2-e][1,2,4]triazolo[1,5-c]pyrimidine (5b). Yield 78%; mp 265 - 267 ℃; IR (KBr): 3040, 1622 cm-1; 1H NMR (CDCl3): δ 9.26 (s, 1H, pyrimidine-H), 8.29 (d, 2H, phenyl, H-2 and H-6), 7.86 (d, J = 5.9 Hz, 1H, thiophene), 7.71 (d, J = 5.9 Hz, thiophene), 7.51 (d, 2H, phenyl, H-3 and H-5); MS: (m/z) 287 (M+, 100), 149 (22), 134 (15). Anal. Calcd. for C13H7ClN4S: C, 54.45; H, 2.46; N, 19.54. Found: C, 54.60; H, 2.30; N, 19.40.

2-p-Tolylthieno[3,2-e][1,2,4]triazolo[1,5-c]pyrimidine (5c). Yield 62%; mp 217 - 218 ℃; IR (KBr): 3040, 2946, 1626, 1330 cm-1; 1H NMR (CDCl3): δ 9.25 (s, 1H, pyrimidine-H), 8.23 (d, 2H, phenyl, H-2 and H-6), 7.87 (d, J = 5.9 Hz, 1H, thiophene), 7.68 (d, J = 5.9 Hz, thiophene), 7.34 (d, 2H, phenyl, H-3 and H-5); MS: (m/z) 266 (M+, 100), 149 (25), 134 (10), 117 (10), 91 (9). Anal. Calcd. for C14H10N4S: C, 63.14; H, 3.78; N, 21.04. Found: C, 63.30; H, 3.70; N, 21.22.

2-(4-Methoxyphenyl)thieno[3,2-e][1,2,4]triazolo[1,5-c]pyrimidine (5d). Yield 60%; mp 236 - 238 ℃; IR (KBr): 3050, 2955, 1630, 1370 cm-1; 1H NMR (CDCl3): δ 9.24 (s, 1H, pyrimidine-H), 8.27 (d, 2H, phenyl, H-2 and H-6), 7.86 (d, J = 5.9 Hz, 1H, thiophene), 7.68 (d, J = 5.9 Hz, thiophene), 7.05 (d, 2H, phenyl, H-3 and H-5), 3.90 (s, 3H, Me); MS: (m/z) 282 (M+, 100), 149 (12), 134 (19). Anal. Calcd. for C14H10N4OS: C, 59.56; H, 3.57; N, 19.85. Found: C, 59.69; H, 3.43; N, 19.99.

2-(4-Bromophenyl)thieno[3,2-e][1,2,4]triazolo[1,5-c]pyrimidine (5e). Yield 70%; mp 244 - 246 ℃; IR (KBr): 3030, 1600 cm-1; 1H NMR (DMSO-d6): δ 9.73 (s, 1H, pyrimidine-H), 8.28 (d, 2H, phenyl, H-2 and H-6), 8.10 (d, J = 5.9 Hz, 1H, thiophene), 7.88 (d, J = 5.9 Hz, thiophene), 7.79 (d, 2H, phenyl, H-3 and H-5); MS: (m/z) 331 (M+). Anal. Calcd. for C13H7BrN4S: C, 47.14; H, 2.13; N, 16.92. Found: C, 47.29; H, 2.25; N, 16.80.

2-(3-Chlorophenyl)thieno[3,2-e][1,2,4]triazolo[1,5-c]pyrimidine (5f). Yield 74%; mp 247 - 249 ℃; IR (KBr): 3045, 1612 cm-1; 1H NMR (CDCl3): δ 9.26 (s, 1H, pyrimidine-H), 8.36 (s, 1H, phenyl, H-2), 8.23 (d, 1H, phenyl, H-6), 7.87 (d, J = 5.9 Hz, 1H, thiophene), 7.71 (d, J = 5.9 Hz, thiophene), 7.51-7.46 (m, 2H, phenyl, H-4 and H-5); MS: (m/z) 287 (M+, 100), 149 (15), 134 (20). Anal. Calcd. for C13H7ClN4S: C, 54.45; H, 2.46; N, 19.54. Found: C, 54.59; H, 2.57; N, 19.60.

2-m-Tolylthieno[3,2-e][1,2,4]triazolo[1,5-c]pyrimidine (5g). Yield 63%; mp 193 - 195 ℃; IR (KBr): 3040, 1635, 1375 cm-1; 1H NMR (CDCl3): δ 9.33 (s, 1H, pyrimidine-H), 8.20 (d, 1H, phenyl, H-6), 7.89 (d, J = 5.9 Hz, 1H, thiophene), 7.68 (d, J = 5.9 Hz, thiophene), 7.53 (t, 1H, phenyl, H-5), 7.17-7.09 (m, 2H, phenyl, H-2 and H-4); MS: (m/z) 266 (M+, 100), 149 (15). Anal. Calcd. for C14H10N4S: C, 63.14; H, 3.78; N, 21.04. Found: C, 63.01; H, 3.67; N, 21.18.

2-(3-Bromophenyl)thieno[3,2-e][1,2,4]triazolo[1,5-c]pyrimidine (5h). Yield 69%; mp 246 - 248 ℃; IR (KBr): 3064, 1622 cm-1; 1H NMR (CDCl3): δ 9.27 (s, 1H, pyrimidine-H), 8.52 (s, 1H, phenyl, H-2), 8.28 (d, 1H, phenyl, H-6), 7.86 (d, J = 5.9 Hz, 1H, thiophene), 7.73 (d, J = 5.9 Hz, thiophene), 7.65 (d, 1H, phenyl, H-4), 7.41 (t, 1H, phenyl, H-5); MS: (m/z) 331 (M+, 100), 134 (20). Anal. Calcd. for C13H7BrN4S: C, 47.14; H, 2.13; N, 16.92. Found: C, 47.32; H, 2.02; N, 17.10.

2-(2-Methoxyphenyl)thieno[3,2-e][1,2,4]triazolo[1,5-c]pyrimidine (5i). Yield 56%; mp 220 - 222 ℃; IR (KBr): 3090, 2975, 1610, 1375 cm-1; 1H NMR (CDCl3): δ 9.26 (s, 1H, pyrimidine-H), 8.17-8.13 (m, 2H, phenyl, H-4 and H-6), 7.88 (d, J = 5.9 Hz, 1H, thiophene), 7.69 (d, J = 5.9 Hz, thiophene), 7.42 (t, 1H, phenyl, H-5), 7.34 (d, 1H, phenyl, H-3), 2.48 (s, 3H, Me); MS: (m/z) 282 (M+, 100), 149 (18), 134 (15). Anal. Calcd. for C14H10N4OS: C, 59.56; H, 3.57; N, 19.85. Found: C, 59.71; H, 3.66; N, 20.01.

References

  1. El-Hawash, S. A.; Habib, N. S.; Fanaki, N. H. Pharmazie 1999,54, 808.
  2. Dickinson, R. P.; Bell, A. W.; Hitchcock, C. A.; Narayama-Swami, S.; Ray, S. J.; Richardson, K.; Troke, P. F. Bioorg. Med. Chem. Lett. 1996, 6, 2031. https://doi.org/10.1016/0960-894X(96)00363-0
  3. Palaska, E.; Sahin, G.; Kelicen, P.; Durlu, N. T.; Altinok, G.Farmaco 2002, 57, 101. https://doi.org/10.1016/S0014-827X(01)01176-4
  4. El-Sherberry, M. A.; El-Ashmawy, M. B.; El-Subbagh, H. I.; El-Emam, A. A.; Badria, F. A. Eur. J. Med. Chem. 1995, 30, 445. https://doi.org/10.1016/0223-5234(96)88255-9
  5. Nagamatsu, T.; Ahmed, S.; Hossion, A. M. L.; Ohno, S. Heterocycles2007, 73, 777. https://doi.org/10.3987/COM-07-S(U)58
  6. Shawali, A. S.; Hassaneen, H. M.; Shurrab, N. Kh. Tetrahedron2008, 64, 10339. https://doi.org/10.1016/j.tet.2008.08.082
  7. Baraldi, P. G.; El-Kasher, H.; Farghaly, A.-R.; Venelle, P.; Fruttarolo, F. Tetrahedron 2004, 60, 5093. https://doi.org/10.1016/j.tet.2004.04.010
  8. Pandey, S. K.; Singh, A.; Singh, A.; Nizamuddin, Eur. J. Med. Chem. 2009, 44, 1188. https://doi.org/10.1016/j.ejmech.2008.05.033
  9. Alagarsamy, V.; Solomon, V. R.; Parthiban, P.; Murugesan, S.; Saravanan, G.; Anjana, G. V. J. Heterocycl. Chem. 2008, 45,709. https://doi.org/10.1002/jhet.5570450312
  10. Alagarsamy, V.; Solomon, V. R.; Murugan, M. Bioorg. Med. Chem. 2007, 15, 4009. https://doi.org/10.1016/j.bmc.2007.04.001
  11. Jo, B. S.; Son, H. Y.; Song, Y.-H. Heterocycles 2008, 75, 3091. https://doi.org/10.3987/COM-08-11465
  12. Song, Y.-H.; Son, H. Y. J. Heterocycl. Chem. 2010, 47
  13. Lee, H. M.; Song, Y.-H. Bull. Korean Chem. Soc.2010, 31, 185. https://doi.org/10.5012/bkcs.2010.31.01.185
  14. Jo, B. S.; Song, Y.-H.; Synth. Commun. 2009,39, 4407. https://doi.org/10.1080/00397910902906545
  15. Song, Y.-H.; Jo, B. S. J. Heterocycl. Chem. 2009,46, 1132. https://doi.org/10.1002/jhet.186
  16. Song, Y.-H.; Jo, B. S.; Lee, H. M. Heterocycl. Commun. 2009, 15, 203. https://doi.org/10.1515/HC.2009.15.3.203
  17. Song, Y.-H.; Jo, B. S. Bull. Korean Chem. Soc. 2009, 30, 969. https://doi.org/10.5012/bkcs.2009.30.4.969
  18. Lee, H. M.; Song, Y.-H. J. Kor. Chem. Soc. 2009, 53, 387. https://doi.org/10.5012/jkcs.2009.53.3.387
  19. Kim, K. H.; Song, Y.-H. Heterocycl. Commun. 2008, 14, 405. https://doi.org/10.1515/HC.2008.14.6.405
  20. Song, Y.-H.; Seo, J. J. Heterocycl. Chem. 2007, 44, 1439. https://doi.org/10.1002/jhet.5570440631
  21. Song, Y.-H. Heterocycl. Commun.2007, 13, 33. https://doi.org/10.1515/HC.2007.13.1.33
  22. Okamuru, T.; Kurogi, Y, Hashimoto, K.; Nishikawa, H.; Nagao, Y. Bioorg. Med. Chem. Lett. 2004, 14, 2443. https://doi.org/10.1016/j.bmcl.2004.03.010
  23. Brown, D. J.; Nagamatsu, T. Aust. J. Chem. 1977, 30, 2515. https://doi.org/10.1071/CH9772515
  24. Lovelette, C. A.; Geagan, J. Heterocycl. Chem. 1982, 19,1345. https://doi.org/10.1002/jhet.5570190618
  25. Loakes, D.; Brown, D. M.; Salisburry, S. A. Tetrahedron Lett. 1998, 39, 3865. https://doi.org/10.1016/S0040-4039(98)00634-0
  26. Shawalli, A. S.; Hassaneen, H. M.; Shurrab, N. K. Heterocycles2008, 75, 1479. https://doi.org/10.3987/COM-07-11311

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