BAZI YENİ 4-SÜBSTİTÜE-3-(MORFOLİNOMETİL)-4H-1,2,4-TRİAZOL-5-TİYOL TÜREVLERİNİN MİKRODALGA YARDIMIYLA SENTEZİ

Year 2019, , 220 - 229, 08.09.2019

Roman Shcherbyna

https://doi.org/10.33483/jfpau.533166

Cited By: 9

Abstract

        Amaç: Bu
çalışmanın amacı, mikrodalga sentez sistemi kullanarak
4-((5-((siklohekzilmetil)tiyo)-4-R₁-4H-1,2,4-triazol-3-il)metil)morfolinler
ile 4-((4-R₁-5-(piridin-2-iltiyo)-4H-1,2,4-triazol-3-il)metil)morfolinlerin
yeni serisini sentezlemektir. 

        Gereç ve Yöntem: Başlangıç
bileşikleri olarak 4-R₁-3-(morfolinometil)-4H-1,2,4-triazol-5-tiyoller
(burada, R=H, methyl, ethyl, phenyl, amino) kullanılır.  Sentez, bir mikrodalga sentez sistemi
Milestone Flexi Wave kullanılarak gerçekleştirildi. Sentezlenen bileşiklerin
yapısı modern analiz yöntemleri olan ¹H NMR, ¹³C
NMR-spektroskopisi, element analizi ve gaz kromatografisi-kütle spektrometresi
(GS/MS) kullanılarak doğrulandı.

        Sonuç ve Tartışma:
Yapılan deney sonucunda sentez yöntemi
mikrodalga ışınımıyla 4-((5-((siklohekzilmetil)tiyo)-4-R₁-4H-1,2,4-triazol-3-il)metil)morfolinler
and 4-((4-R₁-5-(piridin-2-iltiyo)-4H-1,2,4-triazol-3-il)metil)morfolinler
için optimize edilmiştir Tanımlanan tüm koşullar altında reaksiyonların sonuna
kadar geldiği ancak reaksiyonun t = 10 min, T = 160 ^оС parametreleri
ile  teknolojik olarak en uygun olduğu
tespit edilmiştir. Bu yaklaşım enerji maliyetlerini düşürmeyi ve hedef
bileşiklerin verimini arttırmayı sağlamıştır. Sonuç olarak, ileri farmakolojik
çalışmalarda biyolojik bileşikler olarak kullanılabilecek bir yeni 1,2,4-triazol
türevi sınıfı elde edilmiştir.

Keywords

1.2.4-triazol, mikrodalga sentezi, heterosiklik

MICROWAVE-ASSISTED SYNTHESIS OF SOME NEW DERIVATIVES OF 4-SUBSTITUTED-3-(MORPHOLINOMETHYL)-4H-1,2,4- TRIAZOLE-5-THIOLES

Abstract

       
Objective: The purpose of this work is to synthesize new series
of 4-((5-((cyclohexylmethyl)thio)-4-R₁-4H-1,2,4-triazol-3-yl)methyl)morpholines
and 4-((4-R₁-5-(pyridin-2-ylthio)-4H-1,2,4-triazol-3-yl)methyl)morpholines
using a microwave synthesis system.

        Material and Method: As starting compounds are used 4-R₁-3-(morpholinomethyl)-4H-1,2,4-triazole-5-thioles
(where, R₁=H, methyl, ethyl, phenyl, amino). Synthesis was carried
out using a microwave synthesis system Milestone Flexi Wave. The structure of
synthesized compounds is confirmed by the use of modern methods of analysis ¹H
NMR, ¹³C NMR spectroscopy, elemental analysis and gas
chromatography–mass spectrometry (GS/MS).

        Result and Discussion: As a result of the conducted
experiment, the synthesis method is optimized for
4-((5-((cyclohexylmethyl)thio)-4-R₁-4H-1,2,4-triazol-3-yl)methyl)morpholines
and 4-((4-R₁-5-(pyridin-2-ylthio)-4H-1,2,4-triazol-3-yl)methyl)morpholines
by microwave irradiation. It was established that the reactions proceed to the
end in all described conditions, but the reaction with the parameters t=10 min,
T=160 ^оС is the most technologically optimal. This approach has
allowed reducing energy costs and increasing the yield of target
compounds.  As a result, a class of new
derivatives of 1,2,4-triazole has been obtained, which can be used in further
pharmacological studies as valuable biological agents.

Keywords

1.2.4-triazole, microwave-assisted synthesis, heterocyclic

References

• 1. Arnold, F. H. (2018). Directed evolution: bringing new chemistry to life. Angewandte Chemie International Edition, 57(16), 4143-4148.
• 2. Gerry, C. J., & Schreiber, S. L. (2018). Chemical probes and drug leads from advances in synthetic planning and methodology. Nature Reviews Drug Discovery, 17(5), 333.
• 3. Minozzi, C., Caron, A., Grenier‐Petel, J. C., Santandrea, J., & Collins, S. K. (2018). Heteroleptic Copper (I)‐Based Complexes for Photocatalysis: Combinatorial Assembly, Discovery, and Optimization. Angewandte Chemie International Edition, 57(19), 5477-5481.
• 4. Bédard, A. C., Adamo, A., Aroh, K. C., Russell, M. G., Bedermann, A. A., Torosian, J. & Jamison, T. F. (2018). Reconfigurable system for automated optimization of diverse chemical reactions. Science, 361(6408), 1220-1225.
• 5. Mermer, A., Demirbaş, N., Şirin, Y., Uslu, H., Özdemir, Z., & Demirbaş, A. (2018). Conventional and microwave prompted synthesis, antioxidant, anticholinesterase activity screening and molecular docking studies of new quinolone-triazole hybrids. Bioorganic chemistry, 78, 236-248.
• 6. Basoglu Ozdemir, S., Demirbas, N., Demirbas, A., Ayaz, F. A., & Çolak, N. (2018). Microwave‐Assisted Synthesis, Antioxidant, and Antimicrobial Evaluation of Piperazine‐Azole‐Fluoroquinolone Based 1,2,4‐Triazole Derivatives. Journal of Heterocyclic Chemistry, 55(12), 2744-2759.
• 7. Aljohani, G., Said, M. A., Lentz, D., Basar, N., Albar, A., Alraqa, S. Y., & Ali, A. A. S. (2019). Microwave-Assisted Synthesis of Mono-and Disubstituted 4-Hydroxyacetophenone Derivatives via Mannich Reaction: Synthesis, XRD and HS-Analysis. Molecules, 24(3), 590-604.
• 8. Bushueva, I., Parchenko, V., Shcherbyna, R., Safonov, A., Kaplaushenko, A., Gutyj, B., & Hariv, I. (2017). Tryfuzol-new original veterinary drug. J. Fac. Pharm. Ankara/Ankara Ecz. Fak. Derg, 41(1), 42-49.
• 9. Shcherbyna, R., Parchenko, V., Martynyshyn, V., & Hunchak, V. (2018). Evaluation of acute and subacute toxicity of oil liniment based on 4-((5-(decylthio)-4-methyl-4H-1,2,4-triazol-3-yl)methyl)morpholine. J. Fac. Pharm. Ankara/Ankara Ecz. Fak. Derg, 42 (1), 43-52. Retrieved from http://dergipark.gov.tr/jfpanu/issue/42653/514314.
• 10. Shcherbyna, R. O., Danilchenko, D. M., Parchenko, V. V., Panasenko, O. I., Knysh, E. H., Hromyh, N. A., & Lyholat, Y. V. (2017). Studying of 2-((5-R-4-R-1-4H-1, 2, 4-triazole-3-Yl) Thio) acetic acid salts influence on growth and progress of blackberries (KIOWA Variety) propagules. Research Journal of Pharmaceutical Biological and Chemical Sciences, 8(3), 975-979.
• 11. Shcherbyna, R. O., Parchenko, V. V., Safonov, A. A., Bushueva, I. V., Zazharskiy, V. V., Davydenko, P. O. & Borovic, I. V. (2018). Synthesis and research of the impact of new derivatives of 4-R-3 (morpholinomethyl)-4H-1,2,4-triazole-5-thiol on cultural attributes of pathogenic M. Bovis. Research Journal of Pharmaceutical Biological and Chemical Sciences, 9(2), 70-79.
• 12. Samelyuk, Y. G., & Kaplaushenko, A. G. (2014). Synthesis of 3-alkylthio(sulfo)-1,2,4-triazoles, Containing methoxyphenyl substituents at C5atoms, Their antipyretic activity, Propensity to adsorption and acute toxicity. Journal of Chemical and Pharmaceutical Research, 6(5), 1117-1121.
• 13. 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.
• 14. Hulina, Y.S., & Kaplaushenko, A. G. (2018). Synthesis, physicochemical properties and further transformations in the series 5 - ((1H-tetrazol-1-yl) methyl) -4-R-4H-1, 2, 4-triazol-3-thiols. Biopharmaceutical Journal, 10 (1), 26-30.
• 15. Ignatova, T. V., Kaplaushenko, A. H., & Frolova, Y. S. (2018). The synthesis, study of 6-((5-phenethyl-4-R-1,2,4-triazole-3-ylthio)pyridyn-3-yl)-(alkyl, heteryl) methanimines and their derivatives. Žurnal organìčnoï ta farmacevtičnoï hìmìï, 16(4 (64)), 34-39.
• 16. Shcherbyna, R. O. (2014). Pharmacological activity analysis of the 1, 2, 4-triazole derivatives. Pharmaceutical Journal, (4), 145-150.
• 17. Kaplaushenko A. Synthesis, structure and biological activity of 4-mono and 4,5-di-substituted 1,2,4-triazoles-3-thione.(Doctoral dissertation, AG Kaplaushenko- Zaporizhzhya, 2012.-387p).
• 18. Shcherbyna, R. A., Panasenko, A. I., Knysh, E. G., & Varinsky, B. A. (2014). Synthesis and Physicochemical Properties of 2-((4-R-3-(morpholinomethylene)-4H-1,2,4-triazol-5-yl)thio)acetic acids. Aktualʹnì Pitannâ Farmacevtičnoï ì Medičnoï Nauki ta Praktiki, 3 (16), 18-21.