FE(ACAC)₃-CATALYZED ONE-POT SYNTHESIS OF SUBSTITUTED QUINOXALINE DERIVATIVES
DOI:
https://doi.org/10.22159/ijcr.2026v10i2.322Keywords:
Fe(acac)3, Phenyldiamine, Cyclocondensation, Phenacyl bromide, QuinoxalineAbstract
Objective: The study was to develop an efficient and practical method for the synthesis of substituted quinoxaline derivatives, which are known for their significant biological activities and structural versatility, and serve as important building blocks in organic synthesis.
Methods: A series of substituted quinoxaline derivatives were synthesized through a one-pot cyclocondensation reaction between substituted phenyl diamines and phenacyl bromide. The reaction was catalyzed by Fe(acac)₃ and carried out at 60 °C for a duration of 50–80 min.
Resuts: The reaction successfully afforded quinoxaline derivatives (3a–3m) in good to excellent yields ranging from 88–94%. The synthesized compounds exhibited high purity, demonstrating the efficiency of the developed protocol.
Conclusion: The present methodology offers several practical advantages, including a simple one-pot procedure, facile isolation of products, high yields, and an efficient cascading cyclocondensation process. This approach provides an effective and reliable route for the synthesis of substituted quinoxaline derivatives.
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1. Corona P, Carta A, Loriga M, Vitale G, Paglietti G. Synthesis and in vitro antitumor activity of new quinoxaline derivatives. Eur J Med Chem. 2009;44(4):1579-91. doi: 10.1016/j.ejmech.2008.07.025, PMID 18774202.
2. Dietrich B, Diederichsen U. Synthesis of cyclopeptidic analogues of triostin a with quinoxalines or nucleobases as chromophores. Eur J Org Chem. 2005;2005(1):147-53. doi: 10.1002/ejoc.200400548.
3. Nageswar YV, Reddy KH, Ramesh K, Murthy SN. Recent developments in the synthesis of quinoxaline derivatives by green synthetic approaches. Org Prep Proced Int. 2013;45(1):1-27. doi: 10.1080/00304948.2013.743419.
4. Pereira JA, Pessoa AM, Cordeiro MN, Fernandes R, Prudencio C, Noronha JP. Quinoxaline, its derivatives and applications: a state-of-the-art review. Eur J Med Chem. 2015;97:664-72. doi: 10.1016/j.ejmech.2014.06.058, PMID 25011559.
5. Seitz LE, Suling WJ, Reynolds RC. Synthesis and antimycobacterial activity of pyrazine and quinoxaline derivatives. J Med Chem. 2002;45(25):5604-6. doi: 10.1021/jm020310n, PMID 12459027.
6. Cheng G, Sa W, Cao C, Guo L, Hao H, Liu Z. Quinoxaline 1,4-di-N-Oxides: biological activities and mechanisms of actions. Front Pharmacol. 2016;7:64. doi: 10.3389/fphar.2016.00064, PMID 27047380.
7. Loriga M, Piras S, Sanna P, Paglietti G. Quinoxaline chemistry part 7.2-[aminobenzoates] and 2-[aminobenzoylglutamate]-quinoxalines as classical antifolate agents synthesis and evaluation of in vitro anticancer, anti-HIV and antifungal activity. Farmaco. 1997;52(3):157-66. PMID 9212450.
8. Hui X, Desrivot J, Bories C, Loiseau PM, Franck X, Hocquemiller R. Synthesis and antiprotozoal activity of some new synthetic substituted quinoxalines. Bioorg Med Chem Lett. 2006;16(4):815-20. doi: 10.1016/j.bmcl.2005.11.025, PMID 16309903.
9. Maikhuri VK, Prasad AK, Jha A, Srivastava S. Recent advances in the transition metal catalyzed synthesis of quinoxalines: a review. New J Chem. 2021;45(30):13214-46. doi: 10.1039/D1NJ01442K.
10. More SV, Sastry MN, Yao CF. Cerium (IV) ammonium nitrate (CAN) as a catalyst in tap water: a simple proficient and green approach for the synthesis of quinoxalines. Green Chem. 2006;8(1):91-5. doi: 10.1039/B510677J.
11. Bhunia S, Ghosh P, Patra SR. Gold-catalyzed oxidative alkyne functionalization by N−O/S−O/C−O bond oxidants. Adv Synth Catal. 2020;362(18):3664-708. doi: 10.1002/adsc.202000274.
12. Hasaninejad A, Zare A, Mohammadizadeh MR, Karami Z. Synthesis of quinoxaline derivatives via condensation of Aryl-1,2-Diamines with 1,2-diketones using (NH4)6Mo7O24.4H2O as an efficient, mild and reusable catalyst. JICS. 2009;6(1):153-8. doi: 10.1007/BF03246514.
13. Danoun K, Essamlali Y, Amadine O, Mahi H, Zahouily M. Eco-friendly approach to access of quinoxaline derivatives using nanostructured pyrophosphate Na2PdP2O7 as a new, efficient and reusable heterogeneous catalyst. BMC Chem. 2020;14(1):6. doi: 10.1186/s13065-020-0662-z.
14. Pan F, Chen TM, Cao JJ, Zou JP, Zhang W, P. Ga(ClO4)3-catalyzed synthesis of quinoxalines by cycloaddition of α-hydroxyketones and o-phenylenediamines. Tetrahedron Lett. 2012;53(20):2508-10. doi: 10.1016/j.tetlet.2012.02.113.
15. Mohammadi H, Shaterian HR, R. (3-Oxo-[1,2,4]triazolidin-1-yl)bis (butane-1-sulfonic acid) functionalized magnetic γ-Fe2O3 nanoparticles: a novel and heterogeneous nanocatalyst for one-pot and efficient four-component synthesis of novel spiro[indeno[1,2- b]quinoxaline derivatives. Applied Organom Chemis. 2019;33(6):e4901. doi: 10.1002/aoc.4901.
16. Gopalaiah K, Saini A, Chandrudu SN, Rao DC, Yadav H, Kumar B. Copper-catalyzed aerobic oxidative coupling of o-phenylenediamines with 2-aryl/heteroarylethylamines: direct access to construct quinoxalines. Org Biomol Chem. 2017;15(10):2259-68. doi: 10.1039/C7OB00122C, PMID 28240337.
17. Gao J, Ren ZG, Lang JP. One-pot aqueous-phase synthesis of quinoxalines through oxidative cyclization of deoxybenzoins with 1,2-Phenylenediamines catalyzed by a Zwtterionic Cu(II)/calix[4]arene complex. Chin Chem Lett. 2017;28(5):1087-92. doi: 10.1016/j.cclet.2016.12.035.
18. Bera A, Sk M, Singh K, Banerjee D. Nickel-catalysed dehydrogenative coupling of aromatic diamines with alcohols: selective synthesis of substituted benzimidazoles and quinoxalines. Chem Commun (Camb). 2019;55(42):5958-61. doi: 10.1039/C9CC02319D, PMID 31050346.
19. Hamid O, Chari MA, Van Nguyen C, Chen JE, Alshehri SM, Yanmaz E. ZnO-loaded mesoporous silica (KIT-6) as an efficient solid catalyst for production of various substituted quinoxalines. Catal Commun. 2017;90:111-5. doi: 10.1016/j.catcom.2016.10.026.
20. Zhao Z, Yu X, Zhu L, Tan S, Fu W, Wang L. Synthesis of α,β-unsaturated ketones with secondary alcohols and aldehydes catalyzed by Fe(acac)3. Chemistry Select. 2022;7(34):e202202093. doi: 10.1002/slct.202202093.
21. Zhang R, Qin Y, Zhang L, Luo S. Oxidative synthesis of benzimidazoles, quinoxalines and benzoxazoles from primary amines by Ortho-quinone catalysis. Org Lett. 2017;19(20):5629-32. doi: 10.1021/acs.orglett.7b02786, PMID 28968131.
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