R. M. Mohareb, J. Schatz / Bioorg. Med. Chem. 19 (2011) 2707–2713
2713
13C NMR, d: 17.4 (CH2), 40.0 (CH2), 61.4 (oxadiazine C-6), 116.8
(CN), 120.9, 129.3, 130.3, 131.9, 132.7, 134.8, 135.5, 135.6, 138.0
(2C6H4), 164.3, 164.3 (2C@N), 189.4 (CO). m/z (EI, 70 eV): 407
(100%, M+), 408 (20%).
1H NMR (DMSO) d: 2.81 (s, 2H, CH2), 4.27 (s, 2H, pyran CH2), 4.90
(s, 2H, CH2), 7.22–7.39 (m, 8H, 2C6H4). 13C NMR, d: 20.1 (CH2),
41.2 (CH2), 116.2, 116.9 (2CN), 38.6, 78.1, 108.3, 138.9, 158.4 (pyr-
an C), 120.2, 121.8, 122.4, 122.9, 123.4, 125.2, 128.3, 130.2 (2C6H4),
187.3 (CO). 430 (100%, M+), 432 (6%, M+2).
5.1.15. 2-(4-Substitutedcetophenon-x-yl)-3-(4-substituted-phe
nyl)-5-cyano-6-cyanomethylpyran (9a–d)
Acknowledgments
General procedure: To a solution of either 6a (4.75 g, 0.01 mol),
6b (4.41 g, 0.01 mol), 6c (4.41 g, 0.01 mol) or 6d (4.07 g,
0.01 mol) in 1,4-dioxan (50 mL) and acetic acid (10 mL), acryloni-
trile (0.53 g, 0.01 mol) was added. The reaction mixture was heated
under reflux for 6 h, reaction was monitored by TLC, then poured
onto ice/water and the formed solid product, in each case, was col-
lected by filtration.
R.M. Mohareb would like to thank the Alexander von Humboldt
Foundation for the financial support during summer, 2009 through
affording him a fellowship in Germany (Erlangen) to carry out the
present research work.
References and notes
1. Shindy, H. A.; El-Maghraby, M. A.; Eissa, F. M. Dyes Pigm. 2006, 70, 110.
2. Mazouz, F.; Lebreton, L.; Milcent, R.; Burstein, C. Eur. J. Med. Chem. 1988, 23,
441.
5.1.16. 2-(4-Bromoacetophenon-
cyano-6-cyanomethylpyran (9a)
x-yl)-3-(4-bromophenyl)-5-
Crystallized from methanol, yellow crystals. Mp: 180–183 °C in
69% yield. Analysis for C22H14Br2N2O2 M. Wt. 498.17. Calcd: C,
53.04; H, 2.83; Br, 32.08; N, 5.62. Found: C, 53.29; H, 3.11; Br,
3. Forchiassin, M.; Risaliti, A.; Russo, C. Tetrahedron 1981, 37, 2921.
4. Yamazaki, N.; Kibayashi, C. Tetrahedron Lett. 1997, 26, 4623.
5. Singh, S.; Husain, K. l.; Athar, F.; Azam, A. Eur. J. Pharm. Sci. 2005, 25, 255.
6. Kaleta, K.; Fleischhauer, J.; Görls, H.; Beckert, R.; Imhof, W. J. Organomet. Chem.
2009, 23, 3800.
7. Muehlebach, M.; Boeger, M.; Cederbaum, F.; Cornes, D.; Friedmann, A. A.;
Glock, J.; Niderman, T.; Stoller, A.; Wagner, T. Bioorg. Med. Chem. 2009, 17, 4241.
8. Ke, S. Y.; Liu, Q. X.; Wang, N.; Yang, Q.; Li, Z. Eur. J. Med. Chem. 2009, 44, 2113.
9. Borén, L.; Martin-Matute, B.; Xu, Y.; Cordova, A.; Bäckvall, J. E. Chem. Eur. J.
2006, 12, 225.
31.87; N, 5.72. IR (
t
cmÀ1): 3055 (CH aromatic), 2893 (CH2),
2223, 2220 (2 CN), 1693 (CO), 1631 (C@C). 1H NMR (DMSO) d:
2.93 (s, 2H, CH2), 3.21 (s, 2H, pyran CH2), 3.92 (s, 2H, CH2), 7.28–
7.39 (m, 8H, 2C6H4). 13C NMR, d: 20.8 (CH2), 40.9 (CH2), 116.0,
116.8 (2CN), 38.6, 78.8, 108.0, 138.8, 162.0 (pyran C), 120.4,
124.4, 126.9, 130.0, 131.3, 131.4, 132.2, 135.5 (2C6H4), 189.6
(CO). m/z (EI, 70 eV): 498 (8%, M+), 500 (17%, M+2), 479 (100%).
10. Srivastava, R. M.; de Morais, L. P.; de Melo, S. C.; Souto, G. B.; Carpenter de
Carvalho, L. T. Tetrahedron Lett. 2006, 47, 3173.
11. Saracoglu, N. Tetrahedron 2007, 63, 4199.
12. Tahdi, A. S.; Titouani, L.; Soufiaoui, M.; Komiha, N.; Kabbaj, O. K.; Hegazi, S.;
Mazzah, A.; Eddaif, A. Tetrahedron 2002, 58, 1507.
13. Todd, L.; Graybill, R. E.; Carla, T.; Helaszek, M. A.; Ator, J. S. Bioorg. Med. Chem.
Lett. 1995, 5, 1197.
5.1.17. 2-(4-Bromoacetophenon-
cyano-6-cyanomethylpyran (9b)
x-yl)-3-(4-nitrophenyl)-5-
14. Frank, G.; Riddell, E.; Turner, S. Tetrahedron 1979, 35, 1311.
15. Wiessler, M. Tetrahedron Lett. 1975, 16, 2575.
16. Muehlebach, M.; Boeger, M.; Cederbaum, F.; Cornes, D.; Friedmann, A. A.;
Glock, J.; Niderman, T.; Stoller, A.; Wagner, T. Bioorg. Med. Chem. 2009, 17,
4241.
17. Vasiliev, N. V.; Lyashenko, Y. E.; Patalakha, A. E.; Sokolski, G. A. J. Fluorine Chem.
1993, 227.
18. Moody, C. J. Adv. Heterocycl. Chem. 1982, 30, 1.
19. Padwa, A.; Eisenbarth, P. Tetrahedron 1985, 41, 283.
20. Riddell, F. G.; Turner, E. S. Tetrahedron 1979, 35, 1311.
21. Tiecco, M.; Testaferri, L.; Marini, F. Tetrahedron 1996, 52, 11841.
22. Job, A.; Janeck, C. F.; Bettray, W.; Peters, R.; Enders, D. Tetrahedron 2002, 58,
2253.
Crystallized from 1,4-dioxan, orange crystals. Mp: 210–214 °C
in 88% yield. Analysis for C22H14BrN3O4, M. Wt. (464.27). Calcd:
C, 56.91; H, 3.04; Br, 17.21; N, 9.05. Found: C, 57.29; H, 3.11; Br,
31.87; N, 8.92. IR (
t
cmÀ1): 3058 (CH aromatic), 2889 (CH2),
2223, 2220 (2 CN), 1688 (CO), 1634 (C@C). 1H NMR (DMSO) d:
2.82 (s, 2H, CH2), 3.24 (s, 2H, pyran CH2), 3.93 (s, 2H, CH2), 7.31–
7.49 (m, 8H, 2C6H4). 13C NMR, d: 20.4 (CH2), 41.3 (CH2), 116.2,
116.6 (2CN), 38.2, 78.9, 108.2, 138.5, 158.7 (pyran C), 120.9,
123.2, 124.8, 129.6, 130.9, 131.7, 132.0, 134.6 (2C6H4), 188.9
(CO). m/z (EI, 70 eV): 463 (100%), 464 (30%, M+), 466 (3%, M+2).
23. Mohamed, A. A.; Radwan, M. E. Bioorg. Med. Chem. 2007, 15, 1206.
24. Muehlebach, M.; Boeger, M.; Cederbaum, F.; Cornes, D.; Friedmann, A. A.;
Glock, J.; Niderman, T.; Stoller, A.; Wanger, T. Bioorg. Med. Chem. 2009, 17,
4241.
5.1.18. 2-(4-Nitroacetophenon-
cyano-6-cyanomethylpyran (9c)
x-yl)-3-(4-bromophenyl)-5-
25. Von Angerer, E.; Strohmeier, J. J. Med. Chem. 1987, 30, 131.
26. Glamkowski, E. J.; Fortunato, J. M.; Spaulding, T. C.; Wilker, J. C.; Ellis, D. B. J.
Med. Chem. 1985, 28, 66.
27. Unangst, P. C.; Carethers, M. E.; Webster, K.; Janik, G. M.; Robichaud, L. J. J. Med.
Chem. 1984, 27, 1629.
28. Sano, H.; Noguchi, T.; Miyajima, A.; Hashimoto, Y.; Miyachi, H. Bioorg. Med.
Chem. Lett. 2006, 16, 3068.
29. Perregaard, J.; Arnt, J.; Boegesoe, K. P.; Hyttel, J.; Sanchez, C. J. Med. Chem. 1992,
35, 1092.
30. Cole, D. C.; Ellingboe, J. W.; Lennox, W. J.; Mazandarani, H.; Smith, D. L.; Stock, J.
R.; Zhang, G. M.; Zhou, P.; Schechter, L. E. Bioorg. Med. Chem. Lett. 2005, 15, 379.
31. Li, Q.; Li, T. M.; Woods, K. W.; Gu, W. Z.; Cohen, J.; Stoll, V. S.; Galicia, T.;
Hutchins, C.; Frost, D.; Rosenberg, S. H.; Sham, H. L. Bioorg. Med. Chem. Lett.
2005, 15, 2918.
Crystallized from 1,4-dioxan, orange crystals. Mp: 180–182 °C
in 71% yield. Analysis for C22H14BrN3O4, (464.27). C, 56.91; H,
3.04; Br, 17.21; N, 9.05. Found: C, 53.29; H, 3.11; Br, 17.33; N,
9.11. IR (t
cmÀ1): 3054 (CH aromatic), 2884 (CH2), 2227, 2221 (2
CN), 1687 (CO), 1638 (C@C). 1H NMR (DMSO) d: 2.80 (s, 2H, CH2),
3.24 (s, 2H, pyran CH2), 4.91 (s, 2H, CH2), 7.26–7.43 (m, 8H,
2C6H4). 13C NMR, d: 20.2 (CH2), 41.0 (CH2), 116.7, 116.6 (2CN),
38.5, 78.2, 108.0, 138.4, 158.6 (pyran C), 120.8, 121.3, 122.9,
123.0, 124.6, 129.6, 132.0, 134.6 (2C6H4), 188.9 (CO). m/z (EI,
70 eV): 464 (30%, M+), 466 (5%, M+2).
32. Xu, H.; Liu, W. Q.; Fan, L. L.; Chen, Y.; Yang, L. M.; Lv, L.; Zheng, Y. T. Chem.
Pharm. Bull. 2008, 56, 720.
33. Hermecz, I. Adv. Heterocycl. Chem. 2003, 65, 173.
5.1.19. 2-(4-Nitroacetophenon-
cyano-6-cyanomethylpyran (9d)
x-yl)-3-(4-nitrophenyl)-5-
34. Ternon, M.; Outurquin, F.; Paulmier, C. Tetrahedron 2001, 57, 10259.
35. Mohareb, R. M.; Mohamed, A. A. Molecules 2010, 15, 3602.
36. Mohareb, R. M.; El-Arab, E. E.; El-Sharkawy, K. A. Sci. Pharm. 2009, 77, 355.
37. Batty, D.; Langlois, Y. Tetrahedron Lett. 1993, 34, 457.
38. Kennedy, J. W.; Hall, D. G. J. Organomet. Chem. 2003, 680, 263–270.
Crystallized from dilute DMF, deep red crystals. Mp: 169–172 °C
in 77% yield. Analysis for C22H14N4O6 (430.37). C, 61.40; H, 3.28; N,
13.02. Found: C, 61.62; H, 3.38; N, 12.87. IR (
aromatic), 2893(CH2), 2218 (CN), 1638 (C@N), 1623 (C@C).
t
cmÀ1): 3044 (CH