Next Article in Journal
5-(6-Hydroxy-6-methyl-5-oxoheptan-2-yl)-2-methyl Phenyl Acetate
Next Article in Special Issue
tert-Butyl Bis(4′-(Hexyloxy)-[1,1′-biphenyl]-4-yl)carbamate
Previous Article in Journal
Synthesis of Imine Congeners of Resveratrol and Evaluation of Their Anti-Platelet Activity
Previous Article in Special Issue
5-Chloro-8-{[1-(2-chlorobenzyl)-1H-1,2,3-triazol-4-yl]methoxy}quinoline
 
 
Search for Articles:
Title / Keyword
Author / Affiliation / Email
Journal
Article Type
 
 
Advanced Search
 
Section
Special Issue
Volume
Issue
Number
Page
 
Journals
Molbank
Volume 2019
Issue 1
10.3390/M1040
molbank-logo
Submit to this Journal Review for this Journal Propose a Special Issue
► Article Menu

Article Menu

share Share announcement Help format_quote Cite question_answer Discuss in SciProfiles thumb_up
...
Endorse textsms
...
Comment
first_page
settings
Order Article Reprints
Font Type:
Arial Georgia Verdana
Font Size:
Aa Aa Aa
Line Spacing:
Column Width:
Background:
Short Note

2′-Chloro-4-(1-methyl-1H-imidazol-2-yl)-2,4′-bipyridine

by
Dhafer Saber Zinad
1,*,
Dunya L. AL-Duhaidahaw
2 and
Ahmed Al-Amiery
3,*
1
Applied Science Department, University of Technology, Baghdad 10001, Iraq
2
Pharmaceutical Chemistry Department, College of Pharmacy, University of Kufa, AL-Najaf 31001, Iraq
3
Energy and Renewable Energies Technology Center, University of Technology, Baghdad 10001, Iraq
*
Authors to whom correspondence should be addressed.
Molbank 2019, 2019(1), M1040; https://doi.org/10.3390/M1040
Submission received: 17 November 2018 / Revised: 29 November 2018 / Accepted: 9 December 2018 / Published: 22 December 2018
(This article belongs to the Special Issue Metal-Catalyzed Synthesis)
Browse Figure
Review Reports Versions Notes

Abstract

:
The compound 2′-chloro-4-(1-methyl-1H-imidazol-2-yl)-2,4′-bipyridine was obtained with a good yield by the reaction of 2-chloro-4-(1-methyl-1H-imidazol-2-yl)pyridine with (2-chloropyridin-4-yl)boronic acid and structurally characterized by nuclear magnetic resonance (1H-NMR and 13C-NMR), thin-layer chromatography–mass spectrometry (TLC–MS), HPLC, gas chromatography–mass spectrometry (GC–MS), and elemental analysis. The functionalization of the pyridine was achieved by the palladium-catalyzed Suzuki–Miyaura carbon–carbon cross-coupling reaction that afforded the target compound.

1. Introduction

Imidazoles are probably the most well-known heterocyclic compounds which are a common and important feature of a variety of natural products and medicinal agents [1,2,3]. Because of their unique antibacterial and antifungal activities, the imidazole core structure has attracted a huge interest from chemists as a significant medical scaffold [4,5,6]. On the other hand, it is known that bipyridines play a significant role as antibacterial and The antimicrobial activities of both these heterocyclic compounds (imidazole and bipyridine) have raised curiosity about the antimicrobial properties of organic molecules containing these two moieties [7,8,9]. Therefore, in this Short Note and in continuation of previous studies [10,11,12,13,14,15,16,17,18,19,20,21,22,23,24], a new imidazole–bipyridine derivative was synthesized for the first time by a palladium-catalyzed Suzuki–Miyaura carbon–carbon cross-coupling reaction (Scheme 1).

2. Results and Discussion

The 2′-chloro-4-(1-methyl-1H-imidazol-2-yl)-2,4′-bipyridine new imidazole–bipyridine derivative was synthesized by a one-step efficient and straightforward reaction (Scheme 1) based on palladium-catalyzed Suzuki–Miyaura carbon–carbon cross-coupling reaction. The compound 2-chloro-4-(1-methyl-1H-imidazol-2-yl)pyridine was reacted with (2-chloropyridin-4-yl)boronic acid. The best yield was obtained when Pd(PPh3)4 was used as the catalyst (3–5 mol%). The use of palladium acetate Pd(OAc)2 in the presence of XPhos gave similar result in terms of yield. However, the employment of Pd(PPh3)4 is significantly cheaper. Also, a chemo-selective coupling reaction proved to be important to carry out the reaction at 150 °C for 6 h to avoid by-products. Cesium carbonate was optimized as the base for the reaction. The desired compound was characterized by chemical analysis methods, which included nuclear magnetic resonance (NMR), liquid chromatography–mass spectrometry (LC–MS), gas chromatography–mass spectrometry (GC–MS), and elemental analysis. The purity of the target compound was also examined using high-performance liquid chromatography (HPLC).

3. Materials and Methods

All chemicals were purchased from commercial sources unless otherwise specified and were used without further purification. Thin-layer chromatography (TLC) controls were performed for all reactions using fluorescent silica gel 60 F254 plates (Merck, Darmstadt, Germany) and visualized under natural light and UV illumination at 254 and 366 nm. The purity of the target compound was confirmed to be >95%, as determined by reversed-phase high-performance liquid chromatography (HPLC).
Nuclear magnetic resonance (NMR) data were obtained with a Bruker ARX NMR spectrometer (Bruker BioSpin AG, Faellanden, Switzerland) at 250 MHz and on a Bruker AVANCE III HD NMR spectrometer (Bruker BioSpin AG, Faellanden, Switzerland) at 300 MHz at ambient temperature. Chemical shifts are reported in parts per million (ppm) relative to tetramethylsilane (TMS). NMR spectra were calibrated against the (residual proton) peak of the deuterated solvent used. A mass spectrum was recorded on an Advion expression S electrospray ionization mass spectrometer (ESI–MS) (Shimadzu Corporation, Kyoto, Japan) with TLC interface.

Synthesis of 2′-Chloro-4-(1-methyl-1H-imidazol-2-yl)-2,4′-bipyridine

Under an argon atmosphere, a mixture of 2-chloro-4-(1-methyl-1H-imidazol-2-yl)pyridine (0.15 g, 0.775 mmol), (2-chloropyridin-4-yl)boronic acid (0.134 g, 0.853 mmol), and Cs2CO3 (0.378 g, 1.16 mmol) was added to a solution of tetrakis(triphenylphosphine)palladium Pd(PPh3)4 (40 mg, 1.16 mmol) in dioxane (5 mL) solvent. The reaction mixture was stirred and heated in a pressure vial at 150 °C for 6 h. The solvent was evaporated at reduced pressure, and the residue was purified by flash column chromatography (SiO2, DCM/EtOH 98:02), yielding the title compound (0.127 g, 61% yield) as a yellow oil. 1H-NMR (300.13 MHz, DMSO-d6) δ = 3.94 (s, 3H), 7.12 (br. s, 1H), 7.43 (br. s, 1H), 7.84–7.86 (m, 1H), 8.14–8.22 (m, 2H), 8.40–8.41(m, 1H), 8.56 (dd, J = 5.2, 0.6 Hz, 1H) ppm, 8.83 (dd, J = 5.1, 0.7 Hz, 1H). 13C-NMR (75.47 MHz, DMSO-d6) δ = 35.3, 120.0, 120.9, 121.7, 123.4, 125.9, 129.1, 139.8, 143.9, 149.5, 150.9, 151.1, 151.8, 153.0 ppm. MS-ESI m/z: [M + H]+ calculated for C14H11ClN4: 270.7, found: 271.1; HPLC retention time (tR): = 1.492 min. (95.9%). Analysis calculated for C14H11ClN4: C, 62.11; H, 4.10; Cl, 13.09; N, 20.70, Found: C, 62.37; H, 4.35; Cl, 13.33; N, 20.98.

4. Conclusions

In this paper, we developed a facile and efficient chemo-selective method for the synthesis of 2′-chloro-4-(1-methyl-1H-imidazol-2-yl)-2,4′-bipyridine with a good yield by the Suzuki–Miyaura cross-coupling reaction and we characterized the title compound by physicochemical and spectral methods.

Supplementary Materials

The following are available online, Figure S1: HPLC, Figure S2: MS, Figure S3: 13C-NMR, Figure S4: DEPT, Figure S5: 1H-NMR.

Author Contributions

D.S.Z., methodology; D.L.A.-D., characterization; A.A.-A. wrote the manuscript.

Funding

This research was funded by the University of Technology grant number 2017-9-1.

Acknowledgments

The authors acknowledge support of the Institute of Pharmaceutical Sciences at the University of Tübingen, Germany, for providing laboratory and other basic facilities for carrying out experimental work.

Conflicts of Interest

The authors declare no conflict of interest.

References

  1. Zhao, Z.H.; Zhang, X.X.; Jin, L.L.; Yang, S.; Lei, P.S. Synthesis and antibacterial activity of novel ketolides with 11,12-quinoylalkyl side chains. Bioorg. Med. Chem. Lett. 2018, 28, 2358–2363. [Google Scholar] [CrossRef]
  2. Zhang, L.; Wang, L.; Yi, L.; Wang, X.; Zhang, Y.; Liu, J.; Guo, X.; Liu, L.; Shao, C.; Xin, L. A novel antimicrobial substance produced by Lactobacillus rhamnous LS8. Food Control 2017, 73, 754–760. [Google Scholar] [CrossRef]
  3. Journal, E.; Pathology, P. Biological control of grapevine crown gall: Purification and partial characterisation of an antibacterial substance. Eur. J. Plant. Pathol. 2009, 124, 427–437. [Google Scholar]
  4. Hakimelahi, G.H.; Li, P.C.; Moosavimovahedi, A.A.; Chamani, J.; Khodarahmi, G.A.; Ly, T.W.; Valiyev, F.; Leong, M.K.; Hakimelahi, S.; Shia, K.S. Application of the Barton photochemical reaction in the synthesis of 1-dethia-3-aza-1-carba-2-oxacephem: A novel agent against resistant pathogenic microorganisms. Org. Biomol. Chem. 2003, 1, 2461–2467. [Google Scholar] [CrossRef]
  5. Kobayashi, Y.; Doi, M.; Nagata, H.; Kubota, T.; Kume, M.; Murakami, K. The 7α-methoxy substituent in cephem or oxacephem antibiotics enhances in vivo anti-Helicobacter felis activity in mice after oral administration. J. Antimicrob. Chemother. 2000, 45, 807–811. [Google Scholar] [CrossRef]
  6. Tombor, Z.; Greff, Z.; Nyitrai, J.; Kajtár-Peredy, M. Simple and condensed β-lactams, XIX. Synthesis of some new 7-acylamino-2-iso-oxacephem-4-carboxylic acids. Liebigs Ann. 1995, 1995, 825–835. [Google Scholar] [CrossRef]
  7. Zhao, J.; Chen, F.; Han, Y.; Chen, H.; Luo, Z.; Tian, H.; Zhao, Y.; Ma, A.; Zhu, L. Hydrogen-Bonded Organic–Inorganic Hybrid Based on Hexachloroplatinate and Nitrogen Heterocyclic Cations: Their Synthesis, Characterization, Crystal Structures, and Antitumor Activities In Vitro. Molecules 2018, 23, 1397. [Google Scholar] [CrossRef]
  8. Liu, E.; Jian, F. Anionic Water Cluster Polymers [(H2O)18(OH)2]n2n− Is Stabilized by Bis(2,2′-bipyridine) Cupric Chloride [Cu(bipy)2Cl]−. Molecules 2018, 23, 195. [Google Scholar] [CrossRef]
  9. Vasile Scăețeanu, G.; Chifiriuc, M.C.; Bleotu, C.; Kamerzan, C.; Măruţescu, L.; Daniliuc, C.G.; Maxim, C.; Calu, L.; Olar, R.; Badea, M. Synthesis, Structural Characterization, Antimicrobial Activity, and In Vitro Biocompatibility of New Unsaturated Carboxylate Complexes with 2,2′-Bipyridine. Molecules 2018, 23, 157. [Google Scholar] [CrossRef]
  10. Hussain, M.; Hung, N.T.; Khera, R.A.; Malik, I.; Zinad, D.S.; Langer, P. Synthesis of Aryl-Substituted Pyrimidines by Site-Selective Suzuki–Miyura Cross-Coupling Reactions of 2,4,5,6-Tetrachloropyrimidine. Adv. Synth. Catal. 2010, 352, 1429–1433. [Google Scholar] [CrossRef]
  11. Zinad, D.S.; Feist, H.; Villinger, A.; Langer, P. Suzuki-Miyaura reactions of the bis(triflates) of 1,3- and 1,4-dihydroxythioxanthone. Electronic and steric effects on the site-selectivity. Tetrahedron 2012, 68, 711–721. [Google Scholar] [CrossRef]
  12. Zinad, D.S.; Hussain, M.; Villinger, A.; Langer, P. Site-Selective Synthesis of Arylated Indenones by Suzuki–Miyaura Cross-Coupling Reactions of 2,3,5-Tribromoinden-1-one. Eur. J. Org. Chem. 2011, 4212–4221. [Google Scholar] [CrossRef]
  13. Hussain, M.; Zinad, D.S.; Salman, G.A.; Sharif, M.; Villinger, A.; Langer, P. One-Pot Synthesis of Unsymmetrical 2,3-Diarylindoles by Site-Selective Suzuki–Miyaura Reactions of N-Methyl-2,3-dibromoindole. Synlett 2010, 3, 411–414. [Google Scholar]
  14. Ibad, M.F.; Zinad, D.S.; Hussain, M.; Ali, A.; Villinger, A.; Langer, P. One-pot synthesis of arylated 1-methyl-1H-indoles by Suzuki-Miyaura cross-coupling reactions of 2,3-dibromo-1-methyl-1H-indole and 2,3,6-tribromo-1-methyl-1H-indole. Tetrahedron 2013, 69, 7492–7504. [Google Scholar] [CrossRef]
  15. Al-Amiery, A.A.; Musa, A.Y.; Kadhum, A.H.; Mohamad, A.B. The use of umbelliferone in the synthesis of new heterocyclic compounds. Molecules 2011, 16, 6833–6843. [Google Scholar] [CrossRef]
  16. Kadhum, A.A.H.; Al-Amiery, A.A.; Musa, A.Y.; Mohamad, A.B. The Antioxidant Activity of New Coumarin Derivatives. Int. J. Mol. Sci. 2011, 12, 5747–5761. [Google Scholar] [CrossRef] [Green Version]
  17. Al-Amiery, A.A.; Kadhum, A.A.H.; Mohamad, A.A. Antifungal Activities of New Coumarins. Molecules 2012, 17, 5713–5723. [Google Scholar] [CrossRef] [Green Version]
  18. Al-Majedy, Y.K.; Al-Duhaidahawi, D.L.; Al-Azawi, K.F.; Al-Amiery, A.A.; Kadhum, A.A.H.; Mohamad, A.B. Coumarins as Potential Antioxidant Agents Complemented with Suggested Mechanisms and Approved by Molecular Modeling Studies. Molecules 2016, 21, 135. [Google Scholar] [CrossRef]
  19. Al-Amiery, A.A.; Al-Majedy, Y.K.; Kadhum, A.A.H.; Mohamad, A.B. New Coumarin Derivative as an Eco-Friendly Inhibitor of Corrosion of Mild Steel in Acid Medium. Molecules 2015, 20, 366–383. [Google Scholar] [CrossRef]
  20. Al-Majedy, Y.K.; Kadhum, A.A.H.; Al-Amiery, A.A.; Mohamad, A.B. Synthesis and Characterization of Some New 4-Hydroxy-coumarin Derivatives. Molecules 2014, 19, 11791–11799. [Google Scholar] [CrossRef] [Green Version]
  21. Kadhum, A.A.H.; Mohamad, A.B.; Hammed, L.A.; Al-Amiery, A.A.; San, N.H.; Musa, A.Y. Inhibition of Mild Steel Corrosion in Hydrochloric Acid Solution by New Coumarin. Materials 2014, 7, 4335–4348. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  22. Al-Amiery, A.A.; Kadhum, A.A.H.; Kadihum, A.; Mohamad, A.B.; How, C.K.; Junaedi, S. Inhibition of Mild Steel Corrosion in Sulfuric Acid Solution by New Schiff Base. Materials 2014, 7, 787–804. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  23. Al-Amiery, A.A.; Kadhum, A.A.H.; Alobaidy, A.H.M.; Mohamad, A.B.; Hoon, P.S. Novel Corrosion Inhibitor for Mild Steel in HCl. Materials 2014, 7, 662–672. [Google Scholar] [CrossRef] [PubMed]
  24. Al-Amiery, A.A.; Kadhum, A.A.H.; Mohamad, A.B.; Junaedi, S. A Novel Hydrazinecarbothioamide as a Potential Corrosion Inhibitor for Mild Steel in HCl. Materials 2013, 6, 1420–1431. [Google Scholar] [CrossRef] [PubMed] [Green Version]
Molbank 2019 m1040 sch001 550
Scheme 1. Synthesis of 2′-chloro-4-(1-methyl-1H-imidazol-2-yl)-2,4′-bipyridine.
Scheme 1. Synthesis of 2′-chloro-4-(1-methyl-1H-imidazol-2-yl)-2,4′-bipyridine.
Molbank 2019 m1040 sch001

Share and Cite

MDPI and ACS Style

Zinad, D.S.; AL-Duhaidahaw, D.L.; Al-Amiery, A. 2′-Chloro-4-(1-methyl-1H-imidazol-2-yl)-2,4′-bipyridine. Molbank 2019, 2019, M1040. https://doi.org/10.3390/M1040

AMA Style

Zinad DS, AL-Duhaidahaw DL, Al-Amiery A. 2′-Chloro-4-(1-methyl-1H-imidazol-2-yl)-2,4′-bipyridine. Molbank. 2019; 2019(1):M1040. https://doi.org/10.3390/M1040

Chicago/Turabian Style

Zinad, Dhafer Saber, Dunya L. AL-Duhaidahaw, and Ahmed Al-Amiery. 2019. "2′-Chloro-4-(1-methyl-1H-imidazol-2-yl)-2,4′-bipyridine" Molbank 2019, no. 1: M1040. https://doi.org/10.3390/M1040

APA Style

Zinad, D. S., AL-Duhaidahaw, D. L., & Al-Amiery, A. (2019). 2′-Chloro-4-(1-methyl-1H-imidazol-2-yl)-2,4′-bipyridine. Molbank, 2019(1), M1040. https://doi.org/10.3390/M1040

Note that from the first issue of 2016, this journal uses article numbers instead of page numbers. See further details here.

Article Metrics

Back to TopTop