Synthesis of New 3, 5-Disubstituted-1, 2, 4-Triazoles and Evaluation of Antimicrobial Activities

Yıl 2016, Cilt: 6 Sayı: 14, 89 - 98, 15.12.2016

Nurhan Gümrükçüoğlu

Öz

The chemistry of heterocyclic compounds containing five membered 1, 2, 4-triazole nucleus has been an intresting field of study recently. The five membered 1, 2, 4-triazole ring includes two tautomeric forms i.e., 1H-1, 2, 4-triazole, 4H-1, 2, 4-triazole. The triazole derivatives possess extensive spectrum of biological activities such as antibacterial, antifungal, antitubercular, anxiolytic, anticonvulsant, antiinflammatory, analgesic, anticancer, antioxidant activities. The present review is determined view of pharmacological activity of compounds bearing 1, 2, 4-triazole nucleus. First, a series of acylhydrazones 1(a-d) were synthesized by the condensation of iminoester hydrochlorides with acyl hydrazines. The treatment of acylhydrazones with hydrazine hydrate afforded 4-amino-(3, 5-diaryl-4-yl)-4H-1,2, 4- triazoles 2(a-d). A series of new (3, 5-diaryl-4-yl)-4-(arylmethylenamino)-4H-1, 2, 4-triazole derivatives 3(a-d) were prepared in good yields by treatment of 4-amino-(3, 5-diaryl-4-yl)-4H-1, 2, 4-triazoles 2(a-d) with selected aldehydes. Sodium borohydride reduction of 4-arylidenamino derivatives afforded 4- alkylamino-3, 5-dialkyl-1, 2, 4- triazoles 4(a-d). The present review, eight new compounds have been synthesized and characterized by elemental analyses, IR, 1H NMR and 13C NMR spectral data. A series of compounds have been evaluated for their antimicrobial activities. The results show that the synthesized new compounds had effective antimicrobial activities.

Anahtar Kelimeler

Acyl hydrazone, 1, 2, 4-triazole, Schiff base, reduction, antimicrobial activity, antifungal activity

Yeni 3, 5- Disubstitue-1, 2, 4-Triazoller’in Sentezi ve Antimikrobiyal Aktivitelerinin Değerlendirilmesi

Öz

Beş
üyeli 1, 2, 4 triazol halkası içeren heterosiklik bileşiklerin çalışma alanı
son yıllarda giderek dikkat çekmektedir. Bu triazol halkası 1H-1, 2, 4-triazol
ve 4H-1, 2, 4-triazol olmak üzere iki tautomerik formu içerir. Triazol
türevleri, antibakteriyel, antifungal, antitüberküloz, anksiyolitik,
antikonvulsan, anti-inflamatuar, analjezik, antikanser, antioksidan gibi geniş
spektrumlu biyolojik aktivitelere sahiptirler. Bu çalışmada 1, 2, 4-triazol
halkası taşıyan bileşiklerin farmakolojik aktivite gösterdiği belirlenmiştir.
Öncelikle, iminoester hidroklorürlerin açil hidrazinlerle reaksiyonundan açil
hidrazon  (1a-d)’ lar sentezlenmiştir. Daha sonra açil hidrazonların hidrazin
hidrat ile muamelesinden 4-amino-(3,5-diaril-4-il)-4H-1, 2, 4-triazol (2a-d) bileşikleri elde edilmiştir.
Yeni (3,5-diaril-4-il)-4-(arilmetilenamino)-4H-1, 2, 4-triazol (3a-d)’ler,
4-amino-(3,5-diaril-4-il)-4H-1, 2, 4-triazoller (2a-d)’in bazı aldehitlerle reaksiyonlarından yüksek verimlerle
elde edilmiştir. 4-arilidenamino türevlerinin sodyumborhidrür ile
indirgenmesinden ise 4-alkillamino-3,5-dialkil-1, 2, 4- triazol (4a-d) bileşikleri sentezlenmiştir. Bu
çalışmada 8 yeni bileşik sentezlendi ve yapıları elemental analiz, IR, ¹H
NMR, ¹³C NMR spektral verilerle aydınlatıldı. Bileşik serilerinin
antimikrobiyal aktiviteleri değerlendirildi. Sonuçlar sentezlenen yeni
bileşiklerin etkili antimikrobiyal aktiviteye sahip olduğunu göstermektedir.   

Anahtar Kelimeler

Açil hidrazon, 1, 2, 4-triazol, Schiff bazı, İndirgenme, Antimikrobiyal aktivite, Antifungal aktivite

Kaynakça

• Adcock, H. 2002. Pharmageddon: is it too late to tackle growing resistance to anti-infectives? Pharmaceutical Journal, 269: 599–600.
• Ahmad, I., Mehmood, Z., and Mohammed, F. 1998. Screening of some Indian medicinal plants for their antimicrobial properties. Journal Ethnopharmacology, 62: 183-193.
• Amir, M. and Shikha, K. 2004. Synthesis and anti-inflammatory, analgesic, ulcerogenic and lipid peroxidation activities of some new 2-[(2,6-dichloroanilino) phenyl]acetic acid derivatives. European Journal of Medicinal Chemistry, 39: 535-545.
• Awad, L. F. and El Ashry, S. H. 1998. Synthesis and conformational analysis of seco C-nucleosides and their diseco double-headed analogues of the 1, 2, 4-triazole, 1, 2, 4-triazolo [3, 4-b]1, 3, 4-thiadiazole. Carbohydrate Research, 312: 9-22.
• Caglar, Y., Gumrukcuoglu, N., Saka, E. T., Ocak, M., Kantekin, H., Ocak, U. 2012. Phthalocyanine-based fluorescent chemosensor for the sensing of Zn (II) in dimethyl sulfoxide-acetonitrile. Journal of Inclusion Phenomena and Macrocyclic Chemistry, 72: 443-447.
• De Clercq, E. 2001. New developments in anti-HIV chemotherapy, Farmaco, 56: 3–12.
• Gumrukcuoglu, N., Bahadır, Z., Ocak, M., Ocak, U. 2013. Determination of stability constants of triazole ligand carrying naphthol group with heavy metal ions in aqueous solutions. Pakistan Journal of Analytical and Environmental Chemistry, 14: 58-64.
• Gumrukcuoglu, N., Ugras, S., Ugras, H. I., Cakir, U. 2012. Synthesis, extraction and antibacterial studies of some new bis-1, 2, 4- triazole derivatives Part I. Journal Applied Polymer Science, 123: 2011-2019.
• Gumrukcuoglu, N., Sokmen, B. B., Sahin, H., Ugras, S., Sagkal, Y., Ugras, H. I. 2016. Synthesis of New 3,5-disubstituted-1,2,4-Triazoles and Evaluation of Antibacterial, Antiurease and Antioxidant Activities. Journal Chemical Society of Pakistan, 38: 928-936.
• Holla, B. S., Poorjary, K. N., Rao, B. S. and Shivananda, M. K. 2002. Possible Anticancer Agents. European Journal of Medicinal Chemistry, 37: 511-517.
• Jeu, L., Piacenti, F. J., Lyakhovetskiy, A. G., Fung, H. B. 2003. Voriconazole. Clinical Therapeutics, 25: 1321–1381.
• Kunkely, H. and Vogler, A. 2001. Photochemistry of N, N′-Bis (3,5-di-tert-butylsalicylidene)-1,2-Diaminocyclohexane and its Co(II) Complex in Chloroform. Journal of Photochemistry and Photobiology A: Chemistry, 138: 51-54.
• Lu, X., Qin, S. Y., Zhou, Z. Y. and Yam, V. 2003. Synthesis, Structure, and Ion-Binding Studies of Cobalt (II) Complexes with Aza-crown Substituted Salicylaldimine Schiff Base Ligand. Inorganica Chimica Acta, 346: 49-56.
• Mederos, A., Domínguez, S., Hernández-Molina, R., Sanchiz, J and Brito, F. 1999. Coordinating Ability of Ligands Derived From Phenylenediamines. Coordination Chemistry Reviews, 195: 857-911.
• Milcent, R., Redeuilh, C. 1977. Synthesis and properties of aroylhydrazones of ethyl benzoate. Journal Heterocyclic Chemistry, 14: 53-58.
• Ocak, M., Gumrukcuoglu, N., Ocak, U, Buschmann, H. J., Schollmeyer, E. J. 2008. The synthesis of new triazole ligands and determination of complex stability constants with transition metal cations in agueous media. Journal Solution Chemistry, 37: 1489-1497.
• Olive, G. H., Olive, S. 1984. The Chemistry of The Catalyzes Hydrogenation of Carbon Monoxide. Springer, 152: 35-41.
• Palaska, E., Sahin, G., Kelicen, P., Durlu, N. T. and Altınok, G. 2002. Synthesis and 1,3,4-Thia- diazoles and 1,2,4-Triazole-3-thiones. Il Farmaco, 57: 101-107.
• Park, S., Mathur, V. K., and Planalp Roy, P. 1998. Syntheses, Solubilities and Oxygen Absorption Properties of New Cobalt (II) Schiff Base Complexes. Polyhedron, 17: 325-330.
• Poole, K. 2001. Overcoming antimicrobial resistance by targeting resistance mechanisms, Journal of Pharmacy and Pharmacology, 53: 283–294.
• Rahaman, S. H., Choowdhury, H., Bose, D., Ghosh, R., Chen-Hsing, G., Barindra, K., Ghosh, H. 2005. Synthesis, Structure and Properties of Mononuclear Cobalt (II) and Cobalt (III) Pseudohalide Complexes Containing N-Donor Schiff Bases: Synthetic Control of Metal Oxidation Levels. Polyhedron, 24: 1755-1763.
• Sokmen, B. B., Gumrukcuoglu, N., Ugras, S., Sahin, H., Sagkal, Y., Ugras, H. I. 2015. Synthesis, Antibacterial, Antiurease, and Antioxidant Activities of Some New 1,2,4-Triazole Schiff Base and Amine Derivatives. Applied Biochemistry and Biotechnology, 175: 705-714.