Synthesis of Some Novel 3,5-Diaryl-1,2,4-Triazole Derivatives and Investigation of Their Antimicrobial Activities
A series of acylhydrazones (2a-d) was synthesized from the reactions of iminoester hydrochlorides (1a-e) with acyl hydrazines. 2,5-Dialkyl 1,3,4-oxadiazoles (3a-d) were obtained in the same reaction media. The treatment of acylhydrazones with hydrazine hydrate afforded 4-amino-3,5-dialkyl-1,2,4-triazoles (4a-c). The acetylation of 4-amino-3-(4-hydroxyphenyl)-5-phenyl-4H-1,2,4-triazole (4a) produced 4-amino-5-(4-acetoxyphenyl)-3-phenyl-4H-1,2,4-triazole (9), while the acetylation of 4-amino-3-(4-tolyl)-5-phenyl-4H-1,2,4-triazole (4b) gave 4-acetylamino-3-phenyl-5-(4-tolyl)-4H-1,2,4-triazole (10). The treatment of compound 4b with various aromatic aldehydes or acetophenone and 4-nitroacetophenone resulted in the formation of 4-arylidenamino-3,5-dialkyl-4H-1,2,4-triazoles (5a-e and 7a,b). Sodium borohydride reduction of 4-arylidenamino derivatives of 1,2,4-triazoles afforded 4-alkylamino-3,5-dialkyl-4H-1,2,4-triazoles (6a-e and 8a,b). All newly synthesized compounds were screened for their antimicrobial and antifungal activities using agar-well diffusion. Compounds 5c and 6d showed marginal antimicrobial activities against Staphylococcus aureus, while compound 6b displayed moderate antifungal activity towards Candida tropicalis.
Synthesis of Some Novel 3,5-Diaryl-1,2,4-Triazole Derivatives and Investigation of Their Antimicrobial Activities
A series of acylhydrazones (2a-d) was synthesized from the reactions of iminoester hydrochlorides (1a-e) with acyl hydrazines. 2,5-Dialkyl 1,3,4-oxadiazoles (3a-d) were obtained in the same reaction media. The treatment of acylhydrazones with hydrazine hydrate afforded 4-amino-3,5-dialkyl-1,2,4-triazoles (4a-c). The acetylation of 4-amino-3-(4-hydroxyphenyl)-5-phenyl-4H-1,2,4-triazole (4a) produced 4-amino-5-(4-acetoxyphenyl)-3-phenyl-4H-1,2,4-triazole (9), while the acetylation of 4-amino-3-(4-tolyl)-5-phenyl-4H-1,2,4-triazole (4b) gave 4-acetylamino-3-phenyl-5-(4-tolyl)-4H-1,2,4-triazole (10). The treatment of compound 4b with various aromatic aldehydes or acetophenone and 4-nitroacetophenone resulted in the formation of 4-arylidenamino-3,5-dialkyl-4H-1,2,4-triazoles (5a-e and 7a,b). Sodium borohydride reduction of 4-arylidenamino derivatives of 1,2,4-triazoles afforded 4-alkylamino-3,5-dialkyl-4H-1,2,4-triazoles (6a-e and 8a,b). All newly synthesized compounds were screened for their antimicrobial and antifungal activities using agar-well diffusion. Compounds 5c and 6d showed marginal antimicrobial activities against Staphylococcus aureus, while compound 6b displayed moderate antifungal activity towards Candida tropicalis.
___
- M.L. Costales, W.A. Leschick, R.J. Her and J. Weimer, US 5763359 (1998).
- K.C. Joshi, S. Giri and S.C. Bahel, J. Sci. Ind. Res. Sect. C, 21, 315-18 (1962).
- A. ˙Ikizler, N. Demirbas and A.A. ˙Ikizler, J. Het. Chem. 33, 1765-69 (1996).
- N. Demirbas, R. U˘gurluo˘glu and A. Demirbas, Bioorg. Med. Chem. 10, 3717-23 (2002).
- S. Liu, X. Qian, G. Song, J. Chen and W. Chen, J. Florin. Chem. 105, 111-15 (2000).
- A. Almasirad, S.A. Tababani, M. Faizi, A. Kebriaeezadeh, N. Mehrabi, A. Dalvandi and A. ShaŞee, Bioorg. Med. Chem. 14, 6057-59 (2004).
- B.S. Holla, K.N. Poorjary, B.S. Rao and M.K. Shivananda, Eur. J. Med. Chem. 37, 511-17 (2002).
- N. Demirbas, S. Alpay-Karao˘glu, A. Demirbas and K. Sancak, Eur. J. Med. Chem., 39, 793-804 (2004).
- P.E. Goss and K. Strasser-Weippl, Best Pract. Res. Clin. End. Met., 18, 113-30 (2004).
- J.R. Santen, Steroids 68, 559-67 (2003).
- M. Clemons, R.E. Coleman and S. Verma, Cancer Treat. Rev. 30, 325-32 (2004).
- N. Demirbas and R. U˘gurluo˘glu, Turk. J. Chem . 28, 559-71 (2004).
- S. Shujuan, L. Hongxiang, Y. Gao, P. Fan, M. Ba, W. Ge and X. Wang, J. Pharm. Biomed. Anal. 34, 24 (2004).
- G. Werreck, K. Six, G. van den Mootor, L. Baert, J. Peeters and M.E. Brewster, Int. J. Pharm. 251, 165-74 (2003).
- N. Ulusoy, A. G¨ursoy and G. ¨Ot¨uk, Il Farmaco 56 947-52 (2001).
- N. Demirba¸s, A. Demirba¸s, S¸. Alpay-Karao˘glu and E. C¸ elik, ARKIVOC, (i), 75-91 (2005).
- N. Demirbas, A. Demirbas and S¸.A. Karao˘glu, Russian J. Bioorg. Chem. 31, 387-97 (2005).
- M. Kritsanida, A. Mouroutsou, P. Marakos, N. Pouli, S. Garoufalias-Papakonstantinou, C. Pannecouque, M. Witvou and E. De Clerq, Il Farmaco 57, 253-57 (2992).
- B.S. Holla, B. Sarojini, S.B. Rao, P.M. Akberali, N.S. Kumari and N.S. Shetty, Il Farmaco 56, 565-70 (2001).
- G. Turan-Zitouni, Z.A. Kaplancikli, K. Erol and F.S. Kili¸c, Il Farmaco 54, 218-23 (1999).
- B.S. Holla, P.M. Akberali and M.K. Shivananda, Il Farmaco 56, 919-23 (2001).
- L. Navidpour, H. Shafaroodi, K. Abdi, M. Amini, M.H. Ghahremani, A.R. Dehpour and A. ShaŞee, Bioorg. Med. Chem. 14, 2507-17 (2006).
- R. ¨Un and A.A. ˙Ikizler, Chim. Acta Turc. 7, 269-90 (1979).
- O. Bekircan, B. Kahveci and M. K¨u¸c¨uk, Turk. J. Chem. 30, 29-40 (2006).
- M. GolŞer and R. Milcent, Synthesis 12, 946-48 (1979).
- O. Bekircan, PhD Thesis, Institute of Science, Karadeniz Technical University, Trabzon, (2000).
- H. Weidinger and J. Kranz, Chem. Ber. 1049-52 (1963).
- C. Kazak, V.T. Yılmaz, E. Agar and O. Bekircan, Crystal Res. Tech. 41, 607-10 (2006).
- O. Bekircan, B. Kahveci and M. K¨u¸c¨uk, Turk. J. Chem. 30, 26-40 (2006).
- C. Perez, M. Pauli and P. Bazerque, Acta Biol. Med. Experimentalis 15, 113-15 (1990).
- I. Ahmad, Z. Mehmood and F. Mohammed, J. Ethnopharmacology 62, 183-93 (1998).
- N. Demirbas and R. U˘gurluo˘glu, Turk. J. Chem . 28, 679-90 (2004).