3- VE 4-SÜBSTİTÜE-5-((3-FENİLPROPİL)TİYO)-4H-1,2,4-TRİAZOLLERİN MİKRODALGA SENTEZİ

Öz

Amaç: Bu çalışmanın amacı, Milestone Flexi Wave mikrodalga sentez sistemi ile 3- ve 4-sübstitüe-5-((3-fenilpropil)tiyo)-4H-1,2,4-triazolleri sentezlemek ve sentez için en iyi yöntemi belirlemektir.

Gereç ve Yöntem: Başlangıç bileşikleri olan 4-amino-5-(tiyofen-2-il-metil)-4H-1,2,4-triazol-3-tiyol (1) ve 5-(2-bromofenil)-4-fenil-4H-1,2,4-triazol-3-tiyol (3), Zaporizhzhya Devlet Tıp Üniversitesi (Ukrayna) Yabancı Öğrenciler için Doğa Bilimleri ve Toksikolojik Kimya Bölümü’nde sentezlendi. 3- ve 4-Sübstitüe-5-((3-fenilpropil)tiyo)-4H-1,2,4-triazolleri sentezlemek için Milestone Flexi Wave mikrodalga sentez sistemi kullanıldı. Sentezlenen bileşiklerin elementel analizi, Elementar Vario L cube (CHNS) evrensel analiz cihazı ile gerçekleştirildi. 1H-NMR spektrumları (400 MHz), DMSO-d6 içerisinde Varian MR-400 spektrometresi ile çekildi ve ADVASP™ Analiz programı ile analiz edildi. Reaksiyonların tamamlanıp tamamlanmadığı ve elde edilen bileşiklerin tayini, 5977B kütle spektrometre detektörü içeren Agilent 7890B gaz kromatografısi ile gerçekleştirildi.

Sonuç ve Tartışma: Reaksiyon, i-propanol içerisinde ve eşdeğer miktarda sodyum hidroksit varlığında gerçekleştirildi. Başlangıç maddeleri 1 ve 3'e (3-bromopropil)benzen eklendi. Reaksiyonun tam olarak sonlanmasının takibi için farklı reaksiyon süreleri kullanıldı. Sıcaklık, mikrodalga radyasyonu, basınç gibi koşullar değiştirilmedi. Reaksiyon ortamının sıcaklığı 1650C'de, basınç 12.2 bar'da, MW ≈ 540 W'da tutuldu. Reaksiyon süresi 15 dakika, 30 dakika ve 45 dakikaya ayarlandı. 3-(Tiyofen-2-il-metil)-4-amino-5-((3-fenilpropil)tiyo)-4H-1,2,4-triazol (2) elde etmek için en uygun reaksiyon süresi 45 dakikadır. 3-(2-Bromofenil)-4-fenil-5-((3-fenilpropil)tiyo)-4H-1,2,4-triazol (4) için en uygun reaksiyon süresi 30 dakika ısıtma olarak bulundu. Bileşik 2 ve 4 için 1H NMR sinyalleri, önerilen yapı ile uyumludur. Sentezlenen bileşiklerin kimyasal yapılarını doğrulamak için elementel analiz (CHNS) yapıldı ve hesaplanan yüzdeler kabul edilebilir aralıkta bulundu.

Anahtar Kelimeler

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

MICROWAVE SYNTHESIS OF 3- AND 4-SUBSTITUTED-5-((3-PHENYLPROPYL)THIO)-4H-1,2,4-TRIAZOLES

Öz

Objective: The purpose of this work was to synthesize 3- and 4-substituted-5-((3-phenylpropyl)thio) 4H-1,2,4-triazoles by the Milestone Flexi Wave microwave synthesis system and choose the best method of synthesis.

Material and Method: The initial compounds 4-amino-5-(thiophen-2-ylmethyl)-4H-1,2,4-triazole-3-thiol (1) and 5-(2-bromophenyl)-4-phenyl-4H-1,2,4-triazole-3-thiol (3) were synthesized at the Department of Natural Sciences for Foreign Students and Toxicological Chemistry of the Zaporizhzhya State Medical University (Ukraine). Milestone Flexi Wave microwave synthesis system was used to synthesize 3- and 4-substituted-5-((3-phenylpropyl)thio)-4H-1,2,4-triazoles. The elemental analysis of synthesized compounds was established by the universal analyzer Elementar Vario L cube (CHNS). The 1H spectra (at 400 MHz) were recorded in DMSO-d6 on a Varian MR-400 spectrometer and analyzed with ADVASP™ Analyzer program. The gas chromatograph Agilent 7890B with a 5977B mass spectrometry detector (US) was used to define the completeness of the reactions and the individuality of the resulting compounds.

Result and Discussion: The reaction was carried out in i-propanol medium and an equivalent amount of sodium hydroxide. (3-Bromopropyl)benzene was added to starting substances 1 and 3. To study the completeness of the reaction, different reaction times were used. Conditions such as temperature, microwave radiation, pressure were unchanged. The temperature of the reaction mixture was kept at 1650C, pressure 12.2 bar, MW ≈ 540 W. The reaction time was set at 15 minutes, 30 minutes, and 45 minutes. The most effective reaction time for obtaining 3-(thiophen-2-ylmethyl)-4-amino-5-((3-phenylpropyl)thio)-4H-1,2,4-triazole (2) is 45 minutes. The most energy efficient reaction time for 3-(2-bromophenyl)-4-phenyl-5-((3-phenylpropyl)thio)-4H-1,2,4-triazole (4) is 30 minutes heating. The signals of 1H NMR for compounds 2 and 4 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

• 1,2,4-triazole
• synthesis
• 1HNMR
• gas chromatography
• heterocyclic compounds

Teşekkür

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

Kaynakça

1. Frolova, Y , Kaplaushenko, A , Nagornaya, N . (2020). DESIGN, SYNTHESIS, ANTIMICROBIAL AND ANTIFUNGAL ACTIVITIES OF NEW 1,2,4-TRIAZOLE DERIVATIVES CONTAINING 1H-TETRAZOLE MOIETY . Journal of Faculty of Pharmacy of Ankara University , 44 (1) , 70-88 . DOI: 10.33483/jfpau.574001
2. Shcherbyna, R . (2020). AN INVESTIGATION OF THE PHARMACOKINETICS AND POTENTIAL METABOLITES OF POTASSIUM 2-((4-AMINO-5-(MORFOLINOMETYL)-4H-1,2,4-TRIAZOL-3-YL)THIO) ACETATE ON RATS . Journal of Faculty of Pharmacy of Ankara University , 44 (2) , 233-241 . DOI: 10.33483/jfpau.681611
3. Shcherbyna, R , Vashchyk, Y . (2019). THE RESEARCH OF 1,2,4-TRIAZOLE DERIVATIVES HEPATOPROTECTIVE ACTIVITY UNDER TETRACYCLINE AND INFECTIOUS HEPATITIS . Journal of Faculty of Pharmacy of Ankara University , 43 (2) , 135-146 . DOI: 10.33483/jfpau.487173
4. Vashchyk, Y , Shcherbyna, R , Parchenko, V , Bushueva, İ , Gutyj, B , Fotına, H , Fotına, T , Stronskyı, Y . (2020). HISTOLOGICAL STUDY OF A CORRECTIVE INFLUENCE OF A COMPOUND POTASSIUM 2-((4-AMINO-5-(MORPHOLINOMETHYL)-4H-1,2,4-TRIAZOL-3-YL)THIO)ACETATE (PKR-173) ON THE STATE OF CHICKEN'S LIVER UNDER INFECTION BY PSEUDOMONAS AERUGINOSA . Journal of Faculty of Pharmacy of Ankara University , 44 (1) , 1-17 . DOI: 10.33483/jfpau.567757
5. 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 . Journal of Faculty of Pharmacy of Ankara University , 42 (1) , 43-52 . Retrieved from https://dergipark.org.tr/en/pub/jfpanu/issue/42653/514314
6. 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.
7. 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.
8. Shcherbyna, R., et al. "The Development of HPLC-DAD Method for Determination of Active Pharmaceutical Ingredient in the Potassium 2-((4-Amino-5-(Morpholinomethyl)-4H-1,2,4-Triazol-3-Yl)Thio) Acetate Substance." Current Issues in Pharmacy and Medical Sciences, vol. 32, no. 1, 2019, pp. 5-9. SCOPUS, www.scopus.com, doi:10.2478/cipms-2019-0001.

9. 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.
10. 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.
11. 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.
12. Shcherbyna, R . (2019). MICROWAVE-ASSISTED SYNTHESIS OF SOME NEW DERIVATIVES OF 4-SUBSTITUTED-3-(MORPHOLINOMETHYL)-4H-1,2,4-TRIAZOLE-5-THIOLES . Journal of Faculty of Pharmacy of Ankara University , 43 (3) , 220-229 . DOI: 10.33483/jfpau.533166
13. Safonov, A . (2020). MICROWAVE SYNTHESIS OF NEW N-R-3-(ALKYLTHIO)-5-(THIOPHEN-2-YLMETHYL)-1,2,4-TRIAZOL-4-AMINES . Journal of Faculty of Pharmacy of Ankara University , 44 (1) , 89-98 . DOI: 10.33483/jfpau.620599
14. 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.