Synthesis and structural characterization of novel pyrazoline derivatives

Yıl 2021, Cilt: 11 Sayı: 2, 622 - 628, 15.04.2021

Gonca Çelik

https://doi.org/10.17714/gumusfenbil.830149

Cited By: 1

Öz

Pyrazolines, which are nitrogen including five-membered heterocyclic structures, have been used in the organic and pharmaceutical industries. This study aimed was to synthesize and characterizes new series of 3,5-diphenyl-4,5-dihydro-1H-pyrazole derivatives. The new pyrazoline compounds have been synthesized from chalcones and hydrazine hydrate in two steps. In the first step, chalcones were synthesized from 2-amino acetophenone and various substituted benzaldehyde by Claisen-Schmidt condensation at room temperature. In second step, starting from various substituted chalcones derivatives with hydrazine hydrate and glacial acetic acid in anhydrous ethanol were synthesized six novel 3,5-diphenyl-4,5-dihydro-1H-pyrazole derivatives utilizing intramolecular Michael addition reaction in good yields. The structures of the newly synthesized 3,5-diphenyl-4,5-dihydro-1H-pyrazole derivatives are identified via 1H NMR, 13C NMR, FT-IR, and HRMS.

Anahtar Kelimeler

Chalcone, Characterization, Pyrazoline, Synthesis

Yeni pirazolin türevlerinin sentezi ve yapı karakterizasyonu

Öz

Heterosiklik moleküllerin azot içeren 5 halkalı üyesi olan pirazolinler organik ve eczacılık endüstrisinde kullanılırlar. Bu çalışmanın amacı, yeni 3,5-difenil-4,5-dihidro-1H-pirazol türevlerini sentezlemek ve karakterize etmektir. Yeni pirazolin türevleri kalkon ve hidrazin hidrattan iki adımda sentezlendi.İlk adımda, 2-amino asetofenon ve çeşitli substitue benzaldehitlerden oda sıcaklığında Claisen-Schmidt kondenzasyonuyla kalkonlar sentezlendi. İkinci adımda, farklı substitue kalkon türevlerinden başlanarak susuz etanol içinde hidrazin hidrat ile birlikte 6 adet yeni 3,5-difenil-4,5-dihidro-1H-pirazol türevleri molekül içi Michael katılması reaksiyonu kullanılarak iyi verimle sentezlendi. Sentezlenen tüm yeni 3,5-difenil-4,5-dihidro-1H-pirazol türevlerinin yapıları 1H NMR, 13C NMR, FT-IR ve HRMS yardımıyla aydınlatıldı.

Anahtar Kelimeler

Kalkon, , Karakterizasyon, Pirazolin, Sentez

Kaynakça

• Abdel-Halim, M., Tinsley, H., keeton, A. B., Weam, M., Atta, N. H., Hammam, M. A., Hefnawy, A., Hartmann, R. W., Engel, M., Piazza, G. A. and Abadi, A. H. (2020). Discovery of trisubstituted pyrazolines as a novel scaffold for the development of selective phosphodiesterase 5 inhibitors. Bioorganic Chemistry, 104, 104322, https://doi.org/10.1016/j.bioorg.2020.104322.
• Ahmad, A., Husain, A., Khan, S. A., Mujeeb, M. and Bhandari, A. (2016). Synthesis, antimicrobial and antitubercular activities of some novel pyrazoline derivatives. Journal of Saudi Chemical Society, 20(5), 577-584, https://doi.org/10.1016/j.jscs.2014.12.004.
• Arslan, T., Çelik, G., Çelik, H., Şentürk, M., Yaylı, N. and Ekinci, D. (2016). Synthesis and Biological Evaluation of Novel Bischalcone Derivatives as Carbonic Anhydrase Inhibitors. Archiv der Pharmazie, 349(9), 741-748, https://doi.org/10.1002/ardp.201600122.
• Bano, S., Alam, M. S., Javed, K., Dudeja, M., Das, A. K. and Dhulap, A. (2015). Synthesis, biological evaluation and molecular docking of some substituted pyrazolines and isoxazolines as potential antimicrobial agents. European Journal of Medicinal Chemistry, 95, 96-103, https://doi.org/10.1016/j.ejmech.2015.03.031.
• Çelik, G., Arslan, T., Şentürk, M. and Ekinci, D. (2020). Synthesis and characterization of some new pyrazolines and their inhibitory potencies against carbonic anhydrases. Archiv der Pharmazie, 353(3), 1900292, https://doi.org/10.1002/ardp.201900292.
• Çelik, G. (2020). New chalcone-3-O-glycoside derivatives: Synthesis and characterization. Journal of Chemical Research, 44(9-10), 598-601, https://doi.org/10.1177/1747519820915165.
• Delgado, G. E., Liew, S. M., Jamalis, J., Cisterna, J., Cardenas, A. and Brito, I. (2020). Structural characterization and Hirsfeld surface analysis of the pyrazoline 1-(3-(4-iodophenyl)-5-(3-methylthiophen-2-yl)-4,5-dihydro-1H-pyrazol-1-yl) ethan-1-one. Journal of Molecular Structure, https://doi.org/10.1016/j.molstruc.2020.128044.
• Dofe, V. S., Sarkate, A. P., Tiwari, S. V., Lokwani, D. K., Karnik, K. S., Kale, I. A., Dodamani, S., Jalalpure, S. S. and Burra, P. V. L. S. (2020). Ultrasound assisted synthesis of tetrazole based pyrazolines and isoxazolines as potent anticancer agents via inhibition of tubulin polymerization. Bioorganic & Medicinal Chemistry Letters, 30(22), 127592, https://doi.org/10.1016/j.bmcl.2020.127592.
• El Sayed Aly, M. R., El Razek Fodah, H. H .A. and Saleh, S. Y. (2014). Antiobesity, antioxidant and cytotoxicity activities of newly synthesized chalcone derivatives and their metal complexes. European Journal of Medicinal Chemistry, 76, 517-530, https://doi.org/10.1016/j.ejmech.2014.02.021.
• Farooq, S. and Ngaini, Z. (2020). One-Pot and Two-Pot Synthesis of Chalcone Based Mono and Bis-Pyrazolines. Tetrahedron Letters, 61(4), 151416, https://doi.org/10.1016/j.tetlet.2019.151416.
• Hassan, S. Y. (2013). Synthesis, antibacterial and antifungal activity of some new pyrazoline and pyrazole derivatives. Molecules, 18(3), 2683-2711, https://doi.org/10.3390/molecules18032683.
• Jainey, P. J. and Bhat, I. K. (2012). Antitumor, analgesic, and anti-inflammatory activities of synthesized pyrazolines. Journal of Young Pharmacists, 4(2), 82-87, https://doi.org/10.4103/0975-1483.96621.
• Kahriman, N., Haşimoğlu, Z., Serdaroğlu, V., Beriş, F. Ş., Barut B. and Yaylı, N. (2017). Synthesis of Novel Pyrazolines, Their Boron-Fluorine Complexes, and Investigation of Antibacterial, Antioxidant, and Enzyme Inhibition Activities. Archiv der Pharmazie, 350(2), e1600285, https://doi.org/10.1002/ardp.201600285.
• Karthikeyan, M. S., Holla, B. S. and Kumari, N. S. (2007). Synthesis and antimicrobial studies on novel chloro-fluorine containing hydroxy pyrazolines. European Journal of Medicinal Chemistry, 42(1), 30-36, https://doi.org/10.1016/j.ejmech.2006.07.011.
• Li, Y., Wan, J. P. and Wen, C. (2017). Water-acetic acid mediated chemoselective synthesis of pyrazolines via multimolecular domino reactions of enaminones and sulfonyl hydrazines. Tetrahedron, 73(16), 2323-2328, https://doi.org/10.1016/j.tet.2017.03.019.
• Lone, I. H., Khan, K. Z. and Fozdar, B. I. (2014). Synthesis, physicochemical properties, antimicrobial and antioxidant studies of pyrazoline derivatives bearing a pyridyl moiety. Medicinal Chemistry Research, 23(1), 363-369, https://doi.org/10.1007/s00044-013-0643-z.
• Michelini, L. J., Castro, M. R. C., Custodio, J. M. F., Naves, L. F. N., Vaz, W. F., Lobon, G. S., Martins, F. T., Perez, C. N. and Napolitano, H. B. (2018). A novel potencial anticancer chalcone: Synthesis, crystal structure and cytotoxic assay. Journal of Molecular Structure, 1168, 309-315, https://doi.org/10.1016/j.molstruc.2018.05.010.
• Mishra, V. K., Mishra, M., Kashaw, V. and Kashaw, S. K. (2017). Synthesis of 1,3,5-trisubstituted pyrazolines asantimalarial and antimicrobial agents. Bioorganic & Medicinal Chemistry, 25(6), 1949-1962, https://doi.org/10.1016/j.bmc.2017.02.025.
• Patel, N. B., Shaikh, F. M., Patel, H. R. and Rajani, D. (2016). Synthesis of 2-pyrazoline from pyridine based chalcone by conventional and microwave techniques: Their comparison and antimicrobial studies. Journal of Saudi Chemical Society, 20, 451-S456, https://doi.org/10.1016/j.jscs.2013.01.008.
• Raghav, N., Garg, S. and Ravish, I. (2016). Conversion of 2'-substituted chalcones in the presence of BSA as evidenced by 1H NMR studies. International Journal of Biological Macromelecules, 85, 23-28, https://doi.org/10.1016/j.ijbiomac.2015.12.060.
• Rana, M., Arif, R., Khan, F. I., Maurya, V., Singh, R., Faizan, M. I., Yasmeen, S., Dar, S. H., Alam, R., Sahu, A. and Ahmad, T. (2021). Pyrazoline analogs as potential anticancer agents and their apoptosis, molecular docking, MD simulation, DNA binding and antioxidant studies. Bioorganic Chemistry, 108, 104665, https://doi.org/10.1016/j.bioorg.2021.104665.
• Sever, B., Altıntop, M. D., Radwan, M. O., Özdemir, A., Otsuka, M., Fujita, M. and Ciftci, H. I. (2019). Design, synthesis and biological evaluation of a new series of thiazolyl-pyrazolines as dual EGFR and HER2 inhibitors. European Journal of Medicinal Chemistry, 182, 111648, https://doi.org/10.1016/j.ejmech.2019.111648.
• Sever, B., Türkeş, C., Altıntop, M. D., Demir, Y. and Beydemir, Ş. (2020). Thiazolyl-pyrazoline derivatives: In vitro and in silico evaluation as potential acetylcholinesterase and carbonic anhydrase inhibitors. International Journal of Biological Macromolecules, 163, 1970-1988, https://doi.org/10.1016/j.ijbiomac.2020.09.043.
• Solanki, N. S., Yaduvanshi, K. S., Jain, V., Mishra, A. and Marothia, D. (2012). Synthesis of antimicrobial activities of di (substituted phenyl)-2 pyrazoline derivatives. International Journal of PharmTech Research, 4(4), 1464-1470.
• Stefans, N. M., Toigo, J., Maioral, M. F., Jacques, A. V., Chiaradia-Delatorre, L. D., Perondi, D. M., Ribeiro, A. A. B., Bigolin, A., Pirath, I. M. S., Duarte, B. F., Nunes, R. J. and Santos-Silva, M. C. (2019). Synthesis of novel pyrazoline derivatives and the evaluation of death mechanisms involved in their antileukemic activity.Bioorganic & Medicinal Chemistry, 27(2), 375-382, https://doi.org/10.1016/j.bmc.2018.12.012.
• Sun, H., Wang, X., Zhan, M., Liu, J. and Xie, Y. (2013). Facile synthesis of novel tetrasubstituted 1-pyrazolines from Baylis-Hillman adducts and acyl diazomethanes. Tetrahedron Letters, 54(29), 3846-3850, https://doi.org/10.1016/j.tetlet.2013.05.041.
• Yar, M. S., Bakht, M. A., Siddiqui, A. A., Abdullah, M. M. and Clercq, E. D. (2009). Synthesis and evaluation of in vitro antiviral activity of novel phenoxy acetic acid derivatives. Journal of Enzyme Inhibition and Medicinal Chemistry, 24, 876-882, https://doi.org/10.1080/14756360802447917.