Synthesis and Characterization of 1-(4-Chlorobenzyl)-2-(pyridine-2- yl)benzimidazole Bioactive Organic Compound

Abstract

In this study, the organic compound with the general formula 1-(4-chlorobenzyl)-2-(pyridin-2-yl)-1H- benzo[d]imidazole was reacted with 2-(2-pyridyl)benzimidazole with potassium carbonate (K2CO3). It was prepared subsequent reaction with 4-chlorobenzyl chloride. The synthesized organic compound was characterized by standard techniques including IR, UV-VIS, 1H, 13C NMR spectroscopy and ESI-MS spectroscopy. Thermal degradation measurement data of benzimidazole derivative compound were examined. These measurements were made with thermogravimetric analysis (TGA) and differential thermal analysis (DTA) techniques and fluorescence Spectrum values were recorded.

Keywords

• Fluorescence
• pyridyl benzimidazole
• thermal decomposition
• biological activity

1-(4-Klorobenzil)-2-(piridin-2-yl) benzimidazol Biyoaktif Organik Bileşiğinin Sentezi ve Karakterizasyonu

Abstract

Bu çalışmada 1-(4-klorobenzil)-2-(piridin-2-yl)-1H-benzo[d]imidazol genel formülüne sahip organik bileşiği, 2- (2-piridil)benzimidazol’ün potasyum karbonat (K2CO3) ile reaksiyona sokulması ve ardından 4-klorobenzil klorür ile tepkimesi sonucu hazırlandı. Sentezlenen organik bileşik IR, UV-VIS, 1H, 13C NMR spektroskopisi ve ESI-MS spektroskopisi dahil standart tekniklerle karakterize edildi. Benzimidazol türevi bileşiğinin termal bozunma ölçüm verileri incelendi. Bu ölçümler termogravimetrik analiz (TGA) ve diferansiyel termal analiz (DTA) teknikleri ile yapıldı ve floresans spektrum değerleri kaydedildi.

Keywords

• Floresans
• piridil benzimidazol
• termal bozunma
• biyolojik aktivite

References

1. [1] E. Orhan, · Ece Ergun, · Koray Şarkaya, and · Ümit Ergun, “A Novel Benzimidazole-Based Chemosensor for Fluorometric Determination of Zinc Ions,” J. Fluoresc., vol. 1, p. 3, doi: 10.1007/s10895-021-02818-w.
2. [2] A. Kamil et al., “Synthesis, structure–activity relationship and antinociceptive activities of some 2-(2′-pyridyl) benzimidazole derivatives,” Med. Chem. Res., vol. 25, no. 6, pp. 1216–1228, 2016, doi: 10.1007/s00044-016-1560-8.
3. [3] M. Akkurt, S. Öztürk, H. Küçükbay, E. Orhan, and O. Büyükgüngör, “1,3-Bis(2- phenylethyl)benzimidazolium-2-dithiocarboxylate,” Acta Crystallogr. Sect. E Struct. Reports Online, vol. 60, no. 2, pp. 219–222, 2004, doi: 10.1107/S160053680400073X.
4. [4] M. Kose and E. Orhan, “Studies on photochromic benzimidazol[1,2a]pyrrolidin-2-ones from the condensation of 2-methyl-3-benzothienylethylidene- (isopropylidene)succinic anhydride with 1,2-diaminobenzenes,” J. Photochem. Photobiol. A Chem., vol. 177, no. 2–3, pp. 170–176, Jan. 2006, doi: 10.1016/j.jphotochem.2005.05.022.
5. [5] M. Akkurt, S. Karaca, H. Küçükbay, E. Orhan, and O. Büyükgüngör, “Dichlorobis[1-(2- ethoxyethyl)-1H-benz-imidazole-κN 3]nickel(II),” Acta Crystallogr. Sect. E Struct. Reports Online, vol. 61, no. 1, 2005, doi: 10.1107/S1600536804031356.
6. [6] S. Türktekin, M. Akkurt, E. Orhan, F. Zehra Küçükbay, H. Küçükbay, and O. Büyükgüngör, “Dichlorobis[1-(2-ethoxyethyl)-1H-benzimidazole-κ3] cobalt(II),” Acta Crystallogr. Sect. E Struct. Reports Online, vol. 60, no. 9, pp. 1220–1223, 2004, doi: 10.1107/S1600536804018835.
7. [7] M. Gopalakrishnan, P. Sureshkumar, J. Thanusu, V. Kanagarajan, R. Govindaraju, and G. Jayasri, “Journal of Enzyme Inhibition and Medicinal Chemistry A convenient ‘one-pot’ synthesis and in vitro microbiological evaluation of novel 2,7-diaryl-[1,4]-diazepan-5-ones,” doi: 10.1080/14756360701270618.
8. [8] M. Akkurt, S. Öztürk, H. Küçükbay, E. Orhan, and O. Büyükgüngör, “1-Ethyl-3-(2- phenylethyl)benzimidazole-2-selone,” Acta Crystallogr. Sect. E Struct. Reports Online, vol. 60, no. 7, pp. 1263–1266, 2004, doi: 10.1107/S1600536804014977.

9. [9] Z. Kazimierczuk, M. Andrzejewska, J. Kaustova, and V. Klimešova, “Synthesis and antimycobacterial activity of 2-substituted halogenobenzimidazoles,” Eur. J. Med. Chem., vol. 40, no. 2, pp. 203–208, Feb. 2005, doi: 10.1016/J.EJMECH.2004.10.004.
10. [10] E. Orhan, A. Garci, T. Riedel, P. J. Dyson, and B. Therrien, “Cytotoxicity of arene ruthenium metalla-rectangles incorporating bis-pyridyl diimide linkers,” J. Organomet. Chem., vol. 815– 816, 2016, doi: 10.1016/j.jorganchem.2016.05.004.
11. [11] H. Küçükbay, S. Günal, E. Orhan, and R. Durmaz, “Synthesis and antimicrobial activities of some transition metal benzimidazole complexes,” Asian J. Chem., vol. 22, no. 9, pp. 7376–7382, 2010.
12. [12] S. Ö. Yildirim, M. Akkurt, H. Küçükbay, E. Orhan, and O. Büyükgüngör, “6-Nitro-1-(2- phenylethyl)-1H-benzimidazole,” Acta Crystallogr. Sect. E Struct. Reports Online, vol. 61, no. 7, pp. o2038–o2039, Jul. 2005, doi: 10.1107/S1600536805017502/DN6224ISUP2.HKL.
13. [13] Z. Saeed Saify et al., “2-(2 0-Pyridyl) benzimidazole derivatives and their urease inhibitory activity,” doi: 10.1007/s00044-014-1015-z.
14. [14] E. Orhan, A. Garci, and B. Therrien, “Flexible arene ruthenium metalla-prisms,” Inorganica Chim. Acta, vol. 438, pp. 5–9, 2015, doi: 10.1016/j.ica.2015.09.002.
15. [15] M. Kose, E. Orhan, K. Suzuki, A. Tutar, C. S. Ünlü, and Y. Yokoyama, “Preparation and photochromic properties of 2,3-bisarylbenz[f]indenones,” J. Photochem. Photobiol. A Chem., vol. 257, 2013, doi: 10.1016/j.jphotochem.2013.01.012.
16. [16] Ş. Pinar, M. Akkurt, H. Küçükbay, E. Orhan, and O. Büyükgüngör, “Bis[1-(but-2-enyl)-5-nitro-1H-benzimidazole-κN3]- dichlorocobalt(II),” Acta Crystallogr. Sect. E Struct. Reports Online, vol. 62, no. 7, 2006, doi: 10.1107/S160053680602352X.
17. [17] M. Akkurt, S. Karaca, H. Küçükbay, E. Orhan, and O. Büyükgüngör, “1-Benzyl-3-(2- phenethyl)benzimidazolium bromide monohydrate,” Acta Crystallogr. Sect. E Struct. Reports Online, vol. 61, no. 8, 2005, doi: 10.1107/S1600536805021653.
18. [18] M. Akkurt, S. Ö. S. Ö. Yildirim, E. Orhan, H. Küçükbay, and O. Büyükgüngör, “1- Methoxyethyl-5-Nitrobenzimidazole,” Acta Crystallogr. Sect. E Struct. Reports Online, vol. 61, no. 9, pp. 10–12, 2005, doi: 10.1107/S1600536805024591.
19. [19] E. Orhan, A. Garci, and B. Therrien, “Coordination-driven self-assembly of arene ruthenium metalla-rectangles,” Inorganica Chim. Acta, vol. 461, 2017, doi: 10.1016/j.ica.2017.01.033.
20. [20] M. Köse and E. Orhan, “Comparison of photochromic properties and thermal stabilities of fulgide, fulgimide, and benzimidazole[1,2-a]pyrrolidine-2-one derivatives,” Turkish J. Chem., vol. 33, no. 5, 2009, doi: 10.3906/kim-0805-1.
21. [21] M. Kose, E. Orhan, and O. Büyükgüngör, “Synthesis of novel photochromic methyl cyanoacetate-condensed fulgide derivatives,” J. Photochem. Photobiol. A Chem., vol. 188, no. 2–3, pp. 358–363, May 2007, doi: 10.1016/j.jphotochem.2006.12.036.
22. [22] L. Gundogdu, M. Kose, S. Takeuchi, Y. Yokoyama, and E. Orhan, “Synthesis, photochromic and fluorescence properties of new bithiazole-containing diarylethenes as cation sensors,” J. Lumin., vol. 203, no. June, pp. 568–575, Nov. 2018, doi: 10.1016/j.jlumin.2018.06.014.
23. [23] E. Orhan, L. Gundogdu, M. Kose, and Y. Yokoyama, “Synthesis and photochromic properties of 4,5-bisaryl-3(2H)-pyridazinones,” J. Photochem. Photobiol. A Chem., vol. 314, pp. 164–170, Jan. 2016, doi: 10.1016/j.jphotochem.2015.08.025.
24. [24] M. Akkurt, S. Öztürk, H. Küçükbay, E. Orhan, and O. Büyükg̈ ngör, “1-Ethyl-4-phenylethyl-1,4- dihydroquinoxaline-2,3-dione,” Acta Crystallogr. Sect. E Struct. Reports Online, vol. 60, no. 7, pp. 1266–1269, 2004, doi: 10.1107/S1600536804014989.
25. [25] E. Orhan, G. Dülger, · Merve Alpay, · Nilüfer Öksüz, and B. Dülger, “Synthesis, antimicrobial and antiproliferative activities of new self-assembly benzimidazole-bridged aren ruthenium rectangles in human breast cancer cells,” J. Incl. Phenom. Macrocycl. Chem., vol. 102, pp. 45– 54, 2022, doi: 10.1007/s10847-021-01099-x.
26. [26] M. Taha et al., “Synthesis of new 1,2-disubstituted benzimidazole analogs as potent inhibitors of β-Glucuronidase and in silico study,” Arab. J. Chem., vol. 15, no. 1, p. 103505, 2022, doi: 10.1016/j.arabjc.2021.103505.
27. [27] P. Keller et al., “An Antifungal Benzimidazole Derivative Inhibits Ergosterol Biosynthesis and Reveals Novel Sterols,” 2015, doi: 10.1128/AAC.00640-15.
28. [28] B. Kahveci, F. Yilmaz, E. Menteşe, M. Özil, and Ş. A. Karaoǧlu, “Microwave-assisted synthesis of some novel benzimidazole derivatives containing imine function and evaluation of their antimicrobial activity,” J. Heterocycl. Chem., vol. 51, no. 4, pp. 982–990, 2014, doi: 10.1002/JHET.1593.
29. [29] A. Welsh, L. I. Rylands, V. B. Arion, S. Prince, and G. S. Smith, “Synthesis and antiproliferative activity of benzimidazole-based, trinuclear neutral cyclometallated and cationic, N^N-chelated ruthenium(ii) complexes,” Dalt. Trans., vol. 49, no. 4, pp. 1143–1156, 2020, doi: 10.1039/c9dt03902c.
30. [30] A. Schroeder et al., “Treating metastatic cancer with nanotechnology,” Nat. Rev. Cancer, 2012, doi: 10.1038/nrc3180.
31. [31] L. iqa Rylands et al., “Structure-activity relationship studies of antiplasmodial cyclometallated ruthenium(II), rhodium(III) and iridium(III) complexes of 2-phenylbenzimidazoles,” Eur. J. Med. Chem., vol. 161, pp. 11–21, Jan. 2019, doi: 10.1016/J.EJMECH.2018.10.019.
32. [32] L. T. Wu et al., “Design, synthesis and biological evaluation of novel benzimidazole-2- substituted phenyl or pyridine propyl ketene derivatives as antitumour agents,” Eur. J. Med. Chem., vol. 114, pp. 328–336, May 2016, doi: 10.1016/J.EJMECH.2016.03.029.
33. [33] S. Kacar, H. Unver, and V. Sahinturk, “A mononuclear copper(II) complex containing benzimidazole and pyridyl ligands: Synthesis, characterization, and antiproliferative activity against human cancer cells,” Arab. J. Chem., vol. 13, no. 2, pp. 4310–4323, 2020, doi: 10.1016/j.arabjc.2019.08.002. [34] Salahuddin, M. Shaharyar, and A. Mazumder, “Benzimidazoles: A biologically active compounds,” Arab. J. Chem., vol. 10, pp. S157–S173, Feb. 2017, doi: 10.1016/J.ARABJC.2012.07.017. [35] M. Hranjec, K. Starčević, S. K. Pavelić, P. Lučin, K. Pavelić, and G. Karminski Zamola, “Synthesis, spectroscopic characterization and antiproliferative evaluation in vitro of novel Schiff bases related to benzimidazoles,” Eur. J. Med. Chem., vol. 46, no. 6, pp. 2274–2279, Jun. 2011, doi: 10.1016/J.EJMECH.2011.03.008. [36] A. Gellis, H. Kovacic, N. Boufatah, and P. Vanelle, “Synthesis and cytotoxicity evaluation of some benzimidazole-4,7-diones as bioreductive anticancer agents,” Eur. J. Med. Chem., vol. 43, no. 9, pp. 1858–1864, Sep. 2008, doi: 10.1016/J.EJMECH.2007.11.020. [37] H. M. Refaat, “Synthesis and anticancer activity of some novel 2-substituted benzimidazole derivatives,” Eur. J. Med. Chem., vol. 45, no. 7, pp. 2949–2956, Jul. 2010, doi: 10.1016/J.EJMECH.2010.03.022. [38] N. R. Thimmegowda et al., “Synthesis, characterization and evaluation of benzimidazole derivative and its precursors as inhibitors of MDA-MB-231 human breast cancer cell proliferation,” Bioorganic Med. Chem. Lett., vol. 18, no. 1, pp. 432–435, Jan. 2008, doi: 10.1016/J.BMCL.2007.08.078. [39] Ersin Orhan, ”Benzimidazolidin Çekirdeği İçeren Elektronca Zengin Olefinlerin Sentez ve Özellikleri,” Yüksek Lisans, Kimya, İnönü Üniversitesi, Malatya, Türkiye, 2001.