MICROWAVE SYNTHESIS OF NEW 3-(ALKYLTHIO)-5-(THIOPHEN2-YLMETHYL)-1,2,4-TRIAZOL-4-AMINES

Year 2020, Volume: 44 Issue: 1, 89 - 98, 31.01.2020

Andrey Safonov

https://doi.org/10.33483/jfpau.620599

Cited By: 5

Abstract

Objectives: The purpose of this work is to synthesize N-R-3-(alkylthio)-5-(thiophen-2-ylmethyl)-1,2,4-triazol-4-amines
by the Milestone Flexi Wave microwave synthesis system and to prove structure
synthesized compounds.

Materials and Methods: The initial compounds 4-R1-3-(thiophen-2-ylmethyl)-4H-1,2,4-triazole-5-thioles
(1-5) were synthesized at the Department of Toxicological and Inorganic
Chemistry of the Zaporizhzhya State Medical University (Ukraine ). Milestone Flexi Wave microwave synthesis system was
used to synthesize
N-R-3-(alkylthio)-5-(thiophen-2-ylmethyl)-1,2,4-triazol-4-amines. The
elemental analysis of synthesized compounds was established by the universal
analyzer Elementar Vario L cube (CHNS). The 1H spectra (at 400 MHz and 100 MHz)
were recorded in DMSO-d6 on a Varian MR-400 spectrometer and analysed with
ADVASP™ Analyzer program. The completeness of the reactions and the
individuality of the resulting compounds were controlled by the gas
chromatograph Agilent 7890B with a 5977B mass spectrometry detector.

Result and Discussion: The reaction was carried out in an
alcoholic medium by adding a catalytic amount of HCl to 4-R-5-(thiophen-2-ylmethyl)-4H-1,2,4-triazole-3-thiols.
Methyl and i-propyl alcohols were used as alcohols. The mixture was heated for
45 minutes at a temperature of 150 ° C, a pressure 14.4 bar, ΔMW = 200 W.

The signals of 1H NMR for (4a-b, 6a-j) 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.

Keywords

synthesis, 1HNMR, gas chromatography, 1.2.4-triazole, heterocyclic compounds

Thanks

We're grateful to the Zaporizhzhia State Medical University for providing some facilities in carrying out the research.

YENİ 3-(ALKİLTİYO)-5-(TİYOFEN-2-İLMETİL)-1,2,4-TRİAZOL-4-AMİNLERİN MİKRODALGA SENTEZİ

Abstract

Amaç: Bu çalışmanın amacı, Milestone Flexi Wave mikrodalga sentez sistemi ile 3-(alkiltiyo)-5-(tiyofen-2-ilmetil)-1,2,4-triazol-4-aminlerin sentezlenmesi ve sentezlenen bileşiklerin yapısının onaylanmasıdır.

Gereç ve Yöntem: İlk bileşikler 3-(tiyofen-2-ilmetil)-4H-1,2,4-triazol-5-tiyoller (1-5) Zaporizhzhya State Medical Üniversite Toksikolojik ve İnorganik Kimya Anabilim Dalı'nda sentezlendi (Ukrayna). 3-(alkiltiyo)-5-(tiyofen-2-ilmetil)-1,2,4-triazol-4-aminlerin sentezlenmesi için Milestone Flexi Wave mikrodalga sentez sistemi kullanıldı. Sentezlenen
bileşiklerin element analizi evrensel analiz Elementar Vario L küpü (CHNS)
tarafından yapıldı. ¹H spektrumları (400 MHz ve 100 MHz'de), DMSO-d₆'da
bir Varian MR-400 spektrometresi üzerinde kaydedildi ve ADVASP ™ Analyzer
programı ile analiz edildi. Reaksiyonlar ve elde edilen bileşikler, bir 5977B
kütle spektrometre detektörü ile Agilent 7890B gaz kromatografısinde  kontrol edildi.

Sonuç
ve Tartışma:
Reaksiyon, 5-(tiyofen-2-ilmetil)-4H-1,2,4-triazol-3-tiyollere katalitik
miktarda HCI ilave edilerek alkollü bir ortamda gerçekleştirildi. Alkol olarak
metil ve i-propil alkoller kullanıldı.

Karışım, 45 dakika boyunca 150°C
sıcaklıkta, 14.4 bar basınçta, ΔMW = 200 W sıcaklıkta ısıtıldı.

Çözücü olarak asetik asit
kullanıldı. (4a-b, 6a-j) için önerilen yapı, ¹H
NMR sinyalleri ile doğrulandı. Temel
kimyasal yapılarını doğrulamak için sentezlenen bileşikler üzerinde element
analizi (CHNS) yapıldı ve hesaplanan yüzdelerle kabul edilebilir bir uyum
sağladığını gösterdi.

Keywords

1.2.4-triazol, sentez, 1H-NMR, gaz kromatografisi, heterosiklik bileşikler

References

• Arnold, F. H. (2018). Directed Evolution: Bringing New Chemistry To Life. Angewandte Chemie International Edition, 57(16), 4143-4148.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• Shcherbyna, R. O. (2014). Pharmacological Activity Analysis Of The 1,2,4-Triazole Derivatives. Pharmaceutical Journal, (4), 145-150.
• 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).
• 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.
• Safonov A.A., O. I. Panasenko, E. G. Knysh, B.O. Varinsky (2014). Synthesis and physicochemical properties of 4-amino-5-(thiophen-2-ylmethyl)-4H-1,2,4-triazole-3-thiol derivatives. Collection of scientific works of the Ukrainian Military Medical Academy. Problems of military health. 42, 381-385.