2ꢀThiohydantoins and their Sꢀmethylation
Russ.Chem.Bull., Int.Ed., Vol. 53, No. 12, December, 2004 2855
2ꢀMethylthioꢀ3ꢀphenylꢀ5ꢀ(pyridylmethylene)ꢀ3,5ꢀdihydroꢀ
4Hꢀimidazolꢀ4ꢀones (2a—c) (general procedure). Water (10 mL),
EtOH (10 mL), and a 15% aqueous KOH solution (2 mL) were
added to the corresponding 3ꢀphenylꢀ5ꢀ(pyridylmethylene)ꢀ2ꢀ
thioxotetrahydroꢀ4Hꢀimidazolꢀ4ꢀone (1a—c) (1.1 g, 4.1 mmol).
After complete dissolution of the precipitate, iodomethane
(1.18 g, 0.54 mL, 8.2 mmol) was added, and the reaction mixꢀ
ture was stirred for 2—3 h. The precipitate that formed was
filtered off and washed on a filter successively with EtOH
and Et2O.
5. A. A. ElꢀBarbary, A. I. Khodair, E. B. Pedersen, and
C. Nielsen, J. Med. Chem., 1994, 37, 73.
6. A. I. Khodair, H. I. ElꢀSubbagh, and A. A. ElꢀEmam,
Bollettino Chimico Farmaceutico, 1997, 136, 561.
7. A. A. AlꢀObaid, H. I. ElꢀSubbagh, A. I. Khodair, and
M. M. A. ElꢀMazar, AntiꢀCancer Drugs, 1996, 7, 873.
8. G. Kollias, E. Douni, G. Kassotis, and D. Kontoyannis,
Immunogical. Revs, 1999, 169, 175.
9. H. H. Merritt, T. J. Putnam, and W. B. Bywater, J. Pharmaꢀ
cology, 1945, 84, 67.
2ꢀMethylthioꢀ3ꢀphenylꢀ5ꢀ(pyridinꢀ2ꢀylmethylene)ꢀ3,5ꢀdiꢀ
hydroꢀ4Hꢀimidazolꢀ4ꢀone (2a). The yield was 0.8 г (67%),
m.p. 206 °C. Found (%): C, 64.77; H, 4.54; N, 14.25.
C16H13N3OS. Calculated (%): C, 65.08; H, 4.41; N, 14.24.
1H NMR, δ: 8.69 (d, 1 H, H(6), Py, J = 8.3 Hz); 8.53 (d, 1 H,
H(3), Py, J = 4.4 Hz); 8.03 (t, 1 H, H(4), Py, J = 4.4 Hz); 7.46
(m, 6 H, H(5), Py, Ph); 6.88 (s, 1 H, CH=); 2.70 (s, 3 H, Me).
13C NMR, δ: 173.5, 166.7, 165.2, 151.8, 147.9, 138.1, 134.1,
127.5, 127.2, 125.2, 122.1, 121.1, 11.3. IR, ν/cm–1: 1730 (C=O);
1650 (C=N); 1600 (C=C).
10. S. Cortes, Z. K. Liao, D. Watson, and H. Kohn, J. Med.
Chem., 1985, 28, 601.
11. S. M. M. Zaidi, R. K. Satsangi, P. Nasir, R. Argawal, and
S. S. Tiwari, Pharmazie, 1980, 35, 755.
12. S. Suzen, B. T. Demircigil, E. Buyukbingol, and S. A.
Ozkam, N. J. Chem., 2003, 27, 1007.
13. K. KiecꢀKononowicz and J. KarolakꢀWojciechowska, Phosꢀ
phorus, Sulfur, Silicon, Relat. Elem., 1992, 73, 235.
14. A. I. Khodair, Carbohydr. Res., 2001, 331, 445.
15. J. A. Grim and H. G. Petring, Cancer Res., 1967, 27, 1278.
16. M. Arca, F. Demartin, F. A. Devillanova, A. Garau, F. Ifaia,
V. Lippolis, and G. Verani, Inorg. Chem., 1998, 37, 4164.
17. A. M. A. Hassaan, Sulfur Lett., 1991, 13, 1.
18. R. S. Srivastava, R. R. Srivastava, and H. N. Bhargava, Bull.
Soc. Chim. Fr., 1991, 128, 671.
19. M. M. Chowdhry, D. M. Mingos, A. J. White, and D. J.
Williams, J. Chem. Soc., Perkin Trans. 1, 2001, 20, 3495.
20. J. S. Casas, E. E. Castellano, A. Macfas, N. Playa,
A. Sanchez, J. Sordo, J. M. Varela, and J. Zukermanꢀ
Schpector, Inorg. Chim. Acta, 1995, 238, 129.
21. M. M. Chowdhry, A. Burrows, D. M. Mingos, A. J. White,
and D. J. Williams, J. Chem. Soc., Chem. Commun.,
1995, 1521.
2ꢀMethylthioꢀ3ꢀphenylꢀ5ꢀ(pyridinꢀ3ꢀylmethylene)ꢀ3,5ꢀdiꢀ
hydroꢀ4Hꢀimidazolꢀ4ꢀone (2b). The yield was 0.85 g (71%),
m.p. 167 °C. Found (%): C, 65.22; H, 4.09; N, 14.25; S, 10.63.
C
16H13N3OS. Calculated (%): C, 65.08; H, 4.41; N, 14.24;
S, 10.85. 1H NMR, δ: 9.22 (s, 1 H, H(2), Py); 8.69 (d, 1 H,
H(6), Py, J = 8.3 Hz); 8.53 (d, 1 H, H(4), Py, J = 4.4 Hz); 7.46
(m, 6 H, H(5), Py, Ph); 6.88 (s, 1 H, CH=); 2.70 (s, 3 H, Me).
13C NMR, δ: 166.2, 150.8, 148.1, 137.5, 136.1, 128.2, 127.7,
125.7, 122.0, 117.4, 97.0. IR, ν/cm–1: 1740 (C=O); 1610 (C=C);
1650 (C=N).
2ꢀMethylthioꢀ3ꢀphenylꢀ5ꢀ(pyridinꢀ4ꢀylmethylene)ꢀ3,5ꢀdiꢀ
hydroꢀ4Hꢀimidazolꢀ4ꢀone (2c). The yield was 0.73 g (61%),
m.p. 225 °C. 1H NMR, δ: 8.66 (d, 2 H, H(2), H(6), Py, J =
6.1 Hz); 7.97 (d, 2 H, H(3), H(5), Py, J = 6.1 Hz); 7.46 (m, 5 H,
Ph); 6.83 (s, 1 H, CH=); 2.71 (s, 3 H, Me). 13C NMR, δ: 202.4,
168.6, 150.3, 141.1, 138.5, 132.2, 129.6, 127.2, 125.0, 120.2,
13.2. IR, ν/cm–1: 1745 (C=O); 1600 (C=C); 1650 (C=N).
22. V. Zubenko, Trudy L´vovskogo meditsinskogo instituta [Proꢀ
ceedings of the Lvov Medical Institute], 1957, 12, 83 (in Rusꢀ
sian); Chem. Abrstrs, 1960, 54, 21059h.
23. D. A. Hahn and E. Gilman, J. Am. Chem. Soc., 1925,
47, 2941.
This study was financially supported by the Russian
Foundation for Basic Research (Project No. 03ꢀ03ꢀ
32401), the Research Program "Russian Universities"
(Grant 05.03.046), and the Presidium of the Russian
Academy of Sciences (Program "Theoretical and Experiꢀ
mental Studies of the Nature of Chemical Bonding and
Mechanisms of Chemical Reactions and Processes").
24. S.ꢀF. Tan, K.ꢀP. Ang, and Y.ꢀF. Fong, J. Chem. Soc., Perkin
Trans. 2, 1986, 1941.
25. T. Steiner and G. R. Desiraju, J. Chem. Soc., Chem. Commun.,
1998, 891.
26. C. Janiak, J. Chem. Soc., Dalton Trans., 2000, 3885.
27. M. Sheldrick, Acta. Crystallogr., Sect. A, 1990, 46, 467.
28. G. M. Sheldrick, SHELXLꢀ97. Program for the Refinement of
Crystal Structures. University of Göttingen, Göttingen, Gerꢀ
many, 1997.
References
29. V. Chazeau, M. Cussac, and A. Boucherle, Eur. J. Med.
Chem., 1992, 27, 615.
1. US Pat. 3,994,904 (1976); Chem. Abstrs, 1997, 86, 10658m.
2. Czech. Pat. 151,744 (1974); Chem. Abstrs, 1974, 81, 63633b.
3. US Pat. 4,452,798A (1984); Chem. Abstrs, 1985, 101, 38476b.
4. Brit. Pat. 166,967 (1964); Chem. Abstrs, 1965, 62, 7768g.
Received May 12, 2004;
in revised form September 9, 2004