TY - JOUR T1 - Synthesis, Structure and Properties of Novel S-Substituted BIS-1,2,4-Triazoles TT - YENİ S-İKAME EDİLMİŞ BIS-1,2,4-TRİAZOLLERİN SENTEZİ VE FİZİKSEL KİMYASAL ÖZELLİKLERİ AU - Karpun, Yevhen PY - 2021 DA - September Y2 - 2021 DO - 10.52794/hujpharm.973420 JF - Hacettepe University Journal of the Faculty of Pharmacy JO - HUJPHARM PB - Hacettepe University WT - DergiPark SN - 2458-8806 SP - 150 EP - 161 VL - 41 IS - 3 LA - en AB - The aim of the work was to describe the method of combining two 1,2,4-triazole systems in a molecule, the alkylation reaction of the thiol group to obtain the previ- ously undiscovered S-derivatives of 1,2,4-triazole and the fragmentation pathway of the substances under hard ionization using gas chromatography-mass spectrom- etry. The structures of the synthesized compounds were confirmed by elemental analysis, 1H and 13C NMR spectroscopy and GC-MS analysis. The characteristic signals for S-alkyl residues were observed in the region typical for aliphatic com- pounds. The fragmentation of molecules was represented by the gradual cleavage of radicals and the opening of the second 1,2,4-triazole heterocycle. KW - Keywords: 1 KW - heterocyclic compound KW - synthesis KW - fragmentation pathway KW - 1 KW - 2 KW - 4-triazole N2 - Özet. Çalışmanın amacı, bir molekülde iki 1,2,4-triazol sistemini birleştirme yöntemini, daha önce keşfedilmemiş 1,2,4-triazolün S-türevlerini elde etmek için tiyol grubunun alkilasyon reaksiyonunu ve gaz kromatografisi-kütle spektrometrisi kullanılarak sert iyonizasyon altındaki maddelerin parçalanma yolu. Sentezlenen bileşiklerin yapıları element analizi, 1H ve 13C NMR spektroskopisi ve GC-MS analizi ile doğrulandı. S-alkil tortuları için karakteristik sinyaller, alifatik bileşikler için tipik olan bölgede gözlendi. Moleküllerin parçalanması, radikallerin kademeli olarak bölünmesi ve ikinci 1,2,4-triazol heterosiklinin açılması ile temsil edildi. CR - 1. 1. Orlewska, C.; Pancechowska-Ksepko, D.; Foks, H.; Zwolska, Z.; Augustynowicz-Kopec, E. Reactivity of N 1-Dithioester Substituted Pyridinand Pyrazincarboxamidrazones. Phosphorus, Sulfur, and Silicon and the Related Elements, 2006, 181(4), pp. 737–744. https://doi.org/10.1080/10426500500270065 CR - 2. Pellizzari, G.; Gazz Chim Ital, 1911, no. 41, pp. 93. CR - 3. Ji Ram, V.; Sethi, A.; Nath, M.; Pratap, R. Five-Membered Heterocycles. The Chemistry of Heterocycles, 2019, pp. 365. https://doi.org/10.1016/b978-0-08-101033-4.00005-x CR - 4. Ueda, S.; Nagasawa, H. Facile synthesis of 1,2,4-triazoles via a copper-catalyzed tandem addition−oxidative cyclization. Journal of the American Chemical Society, 2009, 131(42), pp. 15080-15081. DOI: https://doi.org/10.1021/ja905056z CR - 5. Huang, H.; Guo, W.; Wu, W.; Li, C.-J.; Jiang, H. Copper-catalyzed oxidative C(sp3)–H functionalization for facile synthesis of 1,2,4-triazoles and 1,3,5-triazines from amidines. Organic Letters, 2015, 17(12), pp. 2894-2897. DOI: https://doi.org/10.1021/acs.orglett.5b00995 CR - 6. Castanedo, G. M.; Seng, P. S.; Blaquiere, N.; Trapp, S.; Staben, S. T. Rapid synthesis of 1,3,5-substituted 1,2,4-triazoles from carboxylic acids, amidines, and hydrazines. The Journal of Organic Chemistry, 2011, 76(4), pp. 1177-1179. DOI: https://doi.org/10.1021/jo1023393 CR - 7. Vidavalur, S.; Nakka, M.; Tadikonda, R.; Rayavarapu, S.; Sarakula, P. A Simple and efficient synthesis of 3,4,5-trisubstituted/n-fused 1,2,4-triazoles via ceric ammonium nitrate catalyzed oxidative cyclization of amidrazones with aldehydes using polyethylene glycol as a recyclable reaction medium. Synthesis, 2014, 47(04), pp. 517-525. DOI: https://doi.org/10.1055/s-0034-1378909 CR - 8. Minozzi, C.; Caron, A.; Grenier-Petel, J.; Santandrea, J.; Collins, S. Heteroleptic copper(I)-based complexes for photocatalysis: combinatorial assembly, discovery, and optimization. Angewandte Chemie International Edition, 2018, 57(19), pp. 5477-5481. DOI: 10.1002/anie.201800144 CR - 9. Arnold, F. Directed evolution: bringing new chemistry to life. Angewandte Chemie International Edition, 2017, 57(16), pp. 4143-4148. DOI: 10.1002/anie.201708408 CR - 10. Klimešová, V.; Zahajská, L.; Waisser, K.; Kaustová, J.; Möllmann, U. Synthesis and antimycobacterial activity of 1,2,4-triazole 3-benzylsulfanyl derivatives. Il Farmaco, 2004, 59(4), pp. 279-288. DOI: 10.1016/j.farmac.2004.01.006 CR - 11. Kapro ´n, B.; Łuszczki, J.J.; Płazi ´nska, A.; Siwek, A.; Karcz, T.; Grybo´s, A.; Nowak, G.; Makuch-Kocka, A.; Walczak, K.; Langner, E. Development of the 1,2,4-triazole-based anticonvulsant drug candidates acting on the voltage-gated sodium channels. Insights from in-vivo, in-vitro, and in-silico studies. Eur. J. Pharm. Sci., 2019, 129, pp. 42–57. https://doi.org/10.1016/j.ejps.2018.12.018 CR - 12. Timur, ˙I.; Kocyigit, Ü.M.; Dastan, T.; Sandal, S.; Ceribası, A.O.; Taslimi, P.; Gulcin, ˙I.; Koparir, M.; Karatepe, M.; Çiftçi, M.J. In vitro cytotoxic and in vivo antitumoral activities of some aminomethyl derivatives of 2,4-dihydro-3H-1,2,4-triazole-3-thiones—Evaluation of their acetylcholinesterase and carbonic anhydrase enzymes inhibition profiles. Biochem. Mol. Toxicol, 2019, 33, pp. 22239–22250 https://doi.org/10.1002/jbt.22239 CR - 13. Mishra, C.B.; Mongre, R.K.; Kumari, S.; Jeong, D.K.; Tiwari, M. Novel Triazole-Piperazine Hybrid Molecules Induce Apoptosis via Activation of the Mitochondrial Pathway and Exhibit Antitumor Efficacy in Osteosarcoma Xenograft Nude Mice Model. ACS Chem. Biol, 2017, 17, pp. 753–768. https://doi.org/10.1021/acschembio.6b01007 CR - 14. Mermer, A.; Demirbaş, N.; Şirin, Y.; Uslu, H.; Özdemir, Z.; Demirbaş, A. Conventional and microwave prompted synthesis, antioxidant, anticholinesterase activity screening and molecular docking studies of new quinolone-triazole hybrids. Bioorganic Chemistry, 2018, 78, pp. 236-248. DOI: 10.1016/j.bioorg.2018.03.017 UR - https://doi.org/10.52794/hujpharm.973420 L1 - https://dergipark.org.tr/en/download/article-file/1888099 ER -