Palladium-Catalyzed Sonogashira Synthesis of Alkynyl Derivatives of Quinoline-5, 8-Dione


  • Mercy A. Ezeokonkwo
  • Sunday N. Okafor
  • Evelyn U. Godwin-Nwakwasi
  • F. N. Ibeanu


Alkynylquinoline-5, 8-diones, Palladium Catalysis, Sonogashira protocol, Terminal alkynes.


The synthesis of various alkynylquinoline-5,8-diones is reported. The intermediate 6,7-dibromoquinoline-5,8-dione was obtained by nitrosation of 8-hydroxyquinoline, followed by reduction and subsequent bromination and oxidation. The coupling reaction of 6,7-dibromoquinoline-5,8-dione with various terminal alkynes via Palladium catalysis gave the alkynylquinoline-5,8-diones in good to excellent yields (50-85% ). The chemical structures of the products were confirmed using spectroscopic methods, which include UV/Visible spectrophotometer, Fourier Transform-Infrared (FT-IR) Spectroscopy, 1H and 13C-NMR Spectroscopy. In vitro antimicrobial activity screening carried out on the compounds against bacterial strains: Escherichia coli 1, Escherichia coli 12, Staphylococcus aureus, Klebsiella pneumonia and Pseudomonas aeroginosa, showed that the synthesized compounds have significant activities (MIC= 0.15-3.20), against the tested organisms. However, compound 5e did not inhibit the growth of Pseudomonas aeroginosa.

Author Biography




. Behforouz, M.; Haddad, J.; Cai, W.; Gu, Z. Chemistry of quinoline-5,8-diones., 63,343-346, 1998.

. Harinath,B.B.; Subba Rao, N. V. Synthesis and fungistatic activity of 5:6- and 5:8- quinoline quinine Sym. Syn Heterocyclic compounds physiol interest, Indian patent 1033af, 069, 1964 ( pub. 1996).

. Schellhammer, C.W.; petterson, S. Derivatives of 5,8-quinoline quinines. Chem. Abstr, Ann, 624,108-119, 53,15211e, 1960.

. Pratt, Y. L.; Drake, N.L. Quinoline quinine V, 6-Chloro- and 7-Chloro-5,8-quinolne quinine. J.Am.Chem.Soc., 82,1155-1161, 1960.

. Brandsma. L. Synthesis of Acetylene, Allenes and Cumulenes: Methods and Techniques: Elsever oxford, 293, 2004.

. Brandsma. L.; Vasilevsky, S.F.; Verkruijase. H.D. Application of transition metal catalysts in organic synthesis, springer Berlin, 179-225, 1998.

. (a). Sonogashira, K.; Tohda, Y.; Hagihara, N. A convenient Syntheses of acetylenes catalytic substitutions of acetylenic hydrogen with bromoalkenes, iodoarenes and bromopyridines. Tetrahedron lett.,50, 4467-4470, 1975.

(b). Cassar. L. Palladium catalyzed synthesis of aryl heterocyclic and vinyl acetylene derivatives. J.organomett.

chem., 93, 253-257, 1975.

(c).Dieck, H.; Heck, F. Palladium catalyzed synthesis of aryl heterocyclic and vinyl acetylene derivatives. J.organomett. chem., 93, 259-263, 1975.

. Thorand, S.; Krause, N.J. Poly( arylene ethynylenes) from synthesis to applications., 1998, 63, 8551-8553, 1998.

. Elangonvan, A.; Wang, Y.H.; Ho, T.I. Sonogashira coupling reaction with diminished homo-coupling. Org.lett., 5, 1841-184, 2003.

. Rossi, R.; Carpita, A.; Bigeili, C. Tetrahedron, 26,523, 1985.

. Bohm. V.P.M.; Hermann, W.A., 6, 3679, 2000.

. Godwin-Nwakwasi, E.U. Utility of Buchwald-Hartwig, Mizoroki-Heck and Suzuki- Miyaura cross-coupling reaction in the synthesis of Non-linear Polycylic phenothiazine derivatives: Ph.D Thesis, university of Nigeria.2011.

. Nnabugwu, M.A. Synthesis of some New Aza Analogues of Angular phenothiazines of industrial interest; Ph.D.Thesis, university of Nigeria, Nsukka, 2009.

. Jun-Heng, L.; Xang, Y.; Xie, Y. Modified palladium-catalyzed Sonogashira cross coupling rractions under copper-, Amine- and solvent-free conditions. J.Org.Chem.; 71,379-381, 2006.

. Perecz, C.; Pauli, M.; Bazergue, P. Antibiotic Assay by the agar-well diffusion method. Acta Biologiae et Medicine Experimental, 15,113-115, 1990.

Onoabedje, E. A.; Okoro, U. C.; Sarka, A.; Knight, D. W.Synthesis and structure of new alkynyl derivatives of phenothizine and phenoxazine. J. Sulfur Chem.; 37:3;269-281, 2016.

. Tsuji J., Palladium reagents and catalysis; new perspective for 21st century chemist. Chichester:Wiley, 2014.

. Thomson. R.H. Studies in the juglone series. 1. Some halogen derivatives and their reaction with aniline. J.Org. Chem.; 13, 377, 1948.

Chinchilla, R.; Najera, C. The Sonogashira reaction: A Booming methodology in synthetic organic chemistry. Chem.Rev., 107, 874-922, 2007.

. Geliman, D.; Buchwald, S.L. Efficient Palladium-catalyzed coupling reactions of aryl chloride and Tosylates with alkynes: use of a copper cocatalyst inhibits the Reaction. Angew.Chem. Int. Ed.; 42, 5993-5996, 2003.

. Reetz, M. T.; De Vries, J.G. The role of TBA- in the cross-coupling. Adv. Mater. 11, 773, 2004.

. Urganokar, S.; Verkade. J.G. Palladium-catalyzed Sonogashira cross-coupling reactions under ligand and copper-free condition. J.Org. Chem.; 69, 5752,2004.

. Mori, A.; Kawashima, J.; Shimada, T.; Suguro, M.; Hirabayashi, K.; Nishihara, Y. TBAF as an activator for the palladium-catalyzed Sonogashira reaction. J.Org.Lett.; 2, 2935, 2000.

. Witulski, B.; Azeon, J.R.; Alayrac, C.;Amuatu, A.; Collot, V.; Rault,S. Sequential Sonogashira and Suzuki cross-coupling reactions in the indole and indazole series. Synthesis, 5, 771, 2005.

. Obasi L. N.; Ukoha P. O.; Chah K. F. Synthesis of some sulphonyl derivatives of aminothiazole and

antimicrobial screening, 35:1, 190-193, 2010.




How to Cite

Ezugwu, J. A., Ezeokonkwo, M. A., Okafor, S. N., Godwin-Nwakwasi, E. U., & Ibeanu, F. N. (2017). Palladium-Catalyzed Sonogashira Synthesis of Alkynyl Derivatives of Quinoline-5, 8-Dione. Asian Journal of Applied Sciences, 5(6). Retrieved from