YENİ N'-SÜBSTİTÜE-2-((5-(TİYOFEN-2-İLMETİL)-4H-1,2,4-TRİAZOL-3-İL)TİYO) ASETOHİDRAZİTLERİN SENTEZ YÖNTEMİ

Öz

Amaç: Bu çalışmanın amacı, bir seri yeni N'-sübstitüe-2-((5-(tiyofen-2-ilmetil)-4H-1,2,4-triazol-3-il)tiyo)asetohidrazit sentezlemektir.

Gereç ve Yöntem: Bileşik (3) (2-((3-(tiyofen-2-ilmetil)-1H-1,2,4-triazol-5-il)tiyo)asetohidrazit), izopropil 2-((3-(tiyofen-2-ilmetil)-1H-1,2,4-triazol-5-il)tiyo)asetat (1)'e hidrazin hidrat ilave edilerek sentezlenmiş ve propan-2-ol içerisinde 3-4 saat geri çeviren soğutucuda bekletilmiştir. Bileşikler (5a-s) (N'-sübstitüe-2-(((3-(tiyofen-2-ilmetil)-1H-1,2,4-triazol-5-il)tiyo)asetohidrazit), 3-(tiyofen-2-ilmetil)-1H-1,2,4-triazol-5-il)tiyo)asetohidrazit (3) aromatik veya heterosiklik aldehit ilave edilerek sentezlenmiştir. Çözücü olarak asetik asit kullanılmıştır. Sentezlenen bileşiklerin yapısı, Elementel analiz (CHNS), 1H-NMR ve Kromatografik kütle spektral analizi kullanılarak doğrulanmıştır.

Sonuç ve Tartışma: Bileşik (3), Bileşik (1)'e hidrazin hidrat ilave edilerek sentezlenmiş ve NH = 2,01 ppm’de (NH2) nedeniyle bir singlet formunda 1H-NMR pik ile karakterize edilmiştir. Bileşikler (5a-s), Bileşik (3)’e aromatik veya heterosiklik aldehit ilave edilerek asetik asit ortamda sentezlenmiştir. Bileşikler (5a-s) için önerilen yapı, 1H-NMR sinyalleri ile doğrulanmıştır. Temel kimyasal yapılarını doğrulamak için sentezlenen bileşikler üzerinde elementel analiz (CHNS) yapılmış ve hesaplanan yüzdelerle kabul edilebilir bir uyum sağladığı gösterilmiştir.

Anahtar Kelimeler

• 1H-NMR
• heterosiklik bileşikler
• sentez
• 1.2.4-triazol

METHOD OF SYNTHESIS NOVEL N'-SUBSTITUTED2-((5-(THIOPHEN-2-YLMETHYL)-4H-1,2,4-TRIAZOL-3-YL)THIO) ACETOHYDRAZIDES

Öz

Objective: The purpose of this work is to synthesize new series of N'-substituted-2-((5-(thiophen-2-ylmethyl)-4H-1,2,4-triazol-3-yl)thio)acetohydrazides.

Material and Method: The compound (3) (2-((3-(thiophen-2-ylmethyl)-1H-1,2,4-triazol-5-yl)thio)acetohydrazide) was synthesized by adding hydrazine hydrate to isopropyl 2-((3-(thiophen-2-ylmethyl)-1H-1,2,4-triazol-5-yl)thio)acetate (1) and refluxed for 3-4 h in propan-2-ol. Synthesis of (5a-s) (N'-substituted-2-((3-(thiophen-2-ylmethyl)-1H-1,2,4-triazol-5-yl)thio)acetohydrazide) was carried out by adding aromatic or heterocyclic aldehyde to 2-((3-(thiophen-2-ylmethyl)-1H-1,2,4-triazol-5-yl)thio)acetohydrazide (3) in acetic acid. The structure of synthesized compounds is confirmed using Elemental analysis (CHNS), 1H-NMR and Chromatographic mass spectral analysis.

Result and Discussion: The compound (3) was synthesized by adding hydrazine hydrate to compound (1) and compound (3) characterized by 1H-NMR peak, as a singlet due to (NH2) at δ=2.01ppm. Synthesis of (5a-s) was carried out by adding aromatic or heterocyclic aldehyde to compound (3) in acetic acid. The signals of 1H NMR for (5a-s) are consented with the proposed structure. The elemental analysis (CHNS) was accomplished for synthesized compounds to confirm their basic chemical structures and revealed acceptable agreement with the calculated percentages.

Anahtar Kelimeler

• 1H-NMR
• heterocyclic compounds
• synthesis
• 1.2.4-triazole

Kaynakça

1. Pattan, S., Gadhave, P., Tambe, V., Dengale, S., Thakur, D., Hiremath, S. V., & Deotarse, P. (2012). Synthesis and evaluation of some novel 1, 2, 4-triazole derivatives for antmicrobial, antitubercular and anti-inflammatory activities. Indian Journal of Chemistry Section B 51(1):297-301.
2. Chen, W., Su, H., Xu, Y., Jin, C. Scientific Reports. 2017.; 7:405–414.
3. Rodionova N., Manukovskaya M., Kolomnikova Ya. et. al. Vestnik Voronezhskogo gosudarstvennogo universiteta inzhenernyih tehnologiy. 2015.; Vol. 66, Iss. 4: 98–103.
4. Shcherbyna R.O. Farmatsevtychnyi chasopys. 2014.; 4: 145–150.
5. Aksonova I. I., Shcherbyna R. O., Panasenko O. I. et. al. Ukrainskyi biofarmatsevtychnyi zhurnal. 2014.; 6: 78–82.
6. Cervantes-Elizarrarás, A., Piloni-Martini, J., Ramírez-Moreno, E., Alanís-García, E., Güemes-Vera, N., Gómez-Aldapa, C. A., del Socorro Cruz-Cansino, N. Ultrasonics Sonochemistry. 2017; Vol. 34: 371–379.
7. Thakkar, S. S., Thakor, P., Doshi, H., & Ray, A. (2017). 1,2,4-triazole and 1,3,4-oxadiazole analogues: synthesis, MO studies, in silico molecular docking studies, antimalarial as DHFR inhibitor and antimicrobial activities. Bioorganic & Medicinal Chemistry. 25(15):4064-4075. doi: 10.1016/j.bmc.
8. Kumar, G. S., Prasad, Y. R., & Chandrashekar, S. M. (2013). Synthesis and pharmacological evaluation of novel 4-isopropylthiazole-4-phenyl-1, 2, 4-triazole derivatives as potential antimicrobial and antitubercular agents. Medicinal Chemistry Research, 22(2), 938-948.

9. Patel, N. B., Khan, I. H., Pannecouque, C., & De Clercq, E. (2013). Anti-HIV, antimycobacterial and antimicrobial studies of newly synthesized 1, 2, 4-triazole clubbed benzothiazoles. Medicinal Chemistry Research, 22(3), 1320-1329.
10. Rud, A. M., Kaplaushenko, A. G., Pruglo, Y. S., & Frolova, Y. S. (2018). Establishment Of Diuretic Activity Indicators For (3-Thio-4-R-4-H-1,2,4-triazole-5-yl)(phenyl)methanols And Their Derivatives. Aktualʹnì Pitannâ Farmacevtičnoï ì Medičnoï Nauki ta Praktiki, 2018(2), 215-219.
11. Saidov, G., Sverdlova, O. and Bakhshiev, N. (1995). Prakticheskoe rukovodstvo po molekuli︠a︡rnoĭ spektroskopii. 1st ed. Sankt-Peterburg: Izd-vo Sankt-Peterburgskogo universiteta.
12. Kazitsena, L. and Kupletskaya, N. (1979). Primenenie UF-, IK-, YaMR - i MАSS - spectrometrii v orhanicheskoy khimii. 2nd ed. Moskow: University of Moscow, p.240.
13. Varynskyi, B., Knysh, Y., Parchenko, V., Panasenko, O., & Kaplaushenko, A. (2015). The study of retention regularities for the potential drug substances of 1,2,4-triazol-3-ylthioacetic acids and their salts series by the method of HPLC/DAD-MS. Journal Of Organic And Pharmaceutical Chemistry, 13(4), 68-75.
14. Tkachenko, A., Zazharsky, V., Bilan, M., & Kovaleva, L. (2010). Some peculiarities of bovis tuberculosis display in long not favourably farm. News of Dniproptrovsk State Agrarian and Economic University, (1), 100-103