A convenient synthesis of 3,6-disubstituted 1,4-dihydro-[1,2,4,5] tetrazines and preparation of new acetic acid derivatives containing 5-oxo-4-phenylamino-4,5- dihydro-[1,2,4]triazole

A series of compounds 8a-e, was synthesized by condensation of compounds 7a-e with ethyl bromoac-etate. The treatment of compounds 8a-e with hydrazine hydrate afforded the corresponding hydrazide derivatives (9a-e). Subsequently, compounds 9a-e were converted to alkylidene hydrazides (lOa-e). Moreover, upon heating in the presence of carboxylic acids, compounds 9a-e unexpectedly gave 1,4-dihydro-[1,2,4,5]tetrazine derivatives (11a-e).

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1. N. Demirbaş, R. Uğurluoğlu and A. Demirbaş, Bioorg. Med. Chem., 10, 3717-23 (2002).
2. A.R. Todeschini, A.N. Miranda, K.C.M. Silva, S.C. Parrini and E. Barreiro, Eur. J. Med. Chem., 33, 189-99(1998).
3. D.G. Rando, D.N. Sato, L. Siqueira, A. Malvezzi, C.Q.F. Leite, A.T.Amaral, F.I. Ferreira and L.C. Tavares,Bioorg. Med. Chem.,10, 557-60 (2002).
4. M.G. Mamolo, V. Falagiani, D. Zampieri, L. Vio and E. Banfi, Farmaco, 56, 587-92 (2001).
5. N. Galic, B. Peric, B. Kojic-Prodic and Z. Cimerman, J. Mol. Stuc., 559, 187-94 (2001).
6. E. Wyrzykiewicz and D. Prukah, J. Het. Chem., 35, 381-87 (1998).
7. H. Reddy and Y. Lirgappa, Ind. J. Het. Chem., 33, 919-23 (1994).
8. A. A.İkizler, E. Uzunali and A. Demirbaş, Indian J. Pharm., 5, 289-92 (2000).
9. S. Ersan, S. Nacak and R. Berkem, Farmaco, 53, 773-76 (1998).
10. G. Turan-Zitouni, Z.A. Kaplancikli, K. Erol and F.S. Kiliç, Farmaco, 54, 218-23 (1999).
11. B. Tozkoparan, N. Gökhan, G. Aktay, E. Yeşilada and M. Ertan, Eur. J. Med. Chem. 35, 743-50 (2000).
12. A. Demirbaş, C.B. Johansson, N. Duman and A.A.İkizler, Acta Pol. Pharm.-Drug Res., 53, 117-23 (1996).
13. H. Yüksek, A. Demirbaş, A. İkizler, C.B. Johansson, C. Çelik and A. İkizler; Arzn.- Forsh. Drug Res.,47,405-09 (1997).
14. A. Demirbaş, C.B. Johansson, N. Duman and A.A. İkizler, Acta Pol. Pharm.-Drug Res., 53, 271-78(1996).
15. E.C. Lawson, W.J. Hoeksra, M.F. Addo, P. Andrade-Gordon, B.P. Damiano, J.A. Kauffman, J.A. Mitchell and B.E. Maryanoff, Bioorg. Med. Chem., 11, 2619-22 (2001).
16. V.J. Ram and A.J. Vlietinck, J. Het. Chem., 25, 253-58 (1988).
17. B. Modzelewska-Banachhiewiez and T. Kaminska, Eur. J. Med. Chem., 36, 93-99 (2001).
18. G. Turan-Zitouni, M. Sıvacı, F.S. Kılıç and K. Erol, Eur. J. Med. Chem., 36, 685-89 (2001).
19. S. Demirayak, K. Benkli and K. Güven, Eur. J. Med. Chem., 35, 1037-40 (2000).
20. S. Demirayak, K. Benkli and K. Güven, Pharm. Acta Helv., 72, 285-90 (1998).
21. B. Tozkoparan, G. Aktay and E. Yesilada, Farmaco, 57, 145-52 (2002).
22. N. Ulusoy, A Gürsoy and G. Ötük, Farmaco, 56, 947-52 (2001).
23. A. Kakefuda, T. Suzuki, T. Tobe, A. Tahara, S. Sakamoto and S. Tsukamoto, Bioorg. Med. Chem., 10,1905-12 (2002).
24. J. Reiter, J. Heterocyclic Chem., 31, 745-48 (1994).
25. F. Malbec, R. Milcent and P. Vicart, J. Het. Chem., 21, 1769-74 (1984).
26. A. İkizler, N. Demirbaş and A.A.İkizler, J. Het. Chem., 33, 1765-69 (1996).
27. A. İkizler, N. Demirbaş and A.A.İkizler, Polish J. Chem., 70, 1114-20 (1996).
28. N. Demirbaş, A. Demirbaş and K. Sancak, Turk. J. Chem., 26, 801-06 (2002).
29. M. Abdel and H. Ismail, Heterocycles, 51, 379-84 (1999).
30. A. Demirbaş, N. Demirbaş and A.A.İkizler, Ind. J. Het. Chem., 9, 87-94 (1999).
31. J.P. Kilburn, J. Lau and R.C.F. Jones, Tetrahedron Lett., 42, 2583-86 (2001).
32. D. Gomes, C.P. Borges and J.C. Pinto, Polymer, 42, 851-59 (2001).
33. A.A. İkizler, R. Ün and Chim. Acta Turc., 7, 269-90 (1979).
34. J.C. Oxley, J.L. Smith and H. Chen, Thermochim. Acta, 384, 91-99 (2002).