Reusable nano-catalyzed green protocols for the synthesis of quinoxalines: an overview

Abstract

Heterocyclic compounds are very widely distributed in nature and are essential for life activities. They play a vital role in the metabolism of all living cells, for example, vitamins and co-enzyme precursors thiamine, riboflavin etc. Quinoxalines are a class of N-heterocycles that are present in a variety of natural and synthetic compounds. The distinct pharmacological activities of quinoxalines have attracted medicinal chemists considerably over the past few decades. Quinoxaline-based compounds possess extensive potential applications as medicinal drugs, presently; more than fifteen drugs are available for the treatment of different diseases. Diverse synthetic protocols have been developed via a one-pot approach using efficient catalysts, reagents, and nano-composites/nanocatalysts etc. But the use of homogeneous and transition metal-based catalysts suffers some demerits such as low atom economy, recovery of catalysts, harsh reaction conditions, extended reaction period, expensive catalysts, the formation of by-products, and unsatisfactory yield of products as well as toxic solvents. These drawbacks have shifted the attention of chemists/researchers to develop green and efficient protocols for synthesizing quinoxaline derivatives. In this context, many efficient methods have been developed for the synthesis of quinoxalines using nanocatalysts or nanostructures. In this review, we have summarized the recent progress (till 2023) in the nano-catalyzed synthesis of quinoxalines using condensation of o-phenylenediamine with diketone/other reagents with plausible mechanistic details. With this review, we hope that some more efficient ways of synthesizing quinoxalines can be developed by synthetic chemists.

Fig. 1. Numbering system in quinoxalines.

Fig. 2. Marketed drugs having quinoxaline ring (highlighted).

Scheme 1. General scheme for synthesis of quinoxalines by the condensation of 1,2-dicarbonyl and aryl 1,2-diamines.

Scheme 2. Synthesis of quinoxalines catalyzed by Fe₃O₄@SiO₂/Schiff base complex of metal ions.

Scheme 3. Synthesis of quinoxalines catalyzed by nano-Fe₃O₄ in aqueous media.

Scheme 4. Application of Fe₃O₄@APTES@isatin nanocatalyst for quinoxaline synthesis.

Scheme 5. Synthesis of quinoxaline using Fe₃O₄@APTES@MOF-199 nanocatalyst.

Scheme 6. Possible mechanism for synthesis of quinoxaline using Fe₃O₄@APTES@MOF-199 nanocatalyst.

Scheme 7. Synthesis of quinoxaline using Fe@SiCN catalyst.

Scheme 8. Synthesis of quinoxaline heterocycles catalyzed by Fe(iii)-Schiff base/SBA-15 in water.

Scheme 9. Application of Fe₃O₄@SiO₂@5-SA catalyst for the synthesis of quinoxalines.

Scheme 10. Fe₃O₄@SiO₂-imidazole-PMA magnetic porous nanosphere catalyzed synthesis of quinoxaline.

Scheme 11. Synthesis of quinoxaline using nano-kaoline/BF₃/Fe₃O₄ nano-catalyst.

Scheme 12. Synthesis of 2,3-diaryl/heteroaryl/2-aryl/heteroaryl quinoxalines using nano-γ-Fe₂O₃–SO₃H catalyst.

Scheme 13. Proposed mechanism for the formation of quinoxalines using nano-γ-Fe₂O₃–SO₃H catalyst.

Scheme 14. Synthesis of quinoxalines over PBA@SMNP.

Scheme 15. Synthesis of quinoxalines using 5% Fe/ZnO nano particles.

Scheme 16. Synthesis of various quinoxalines catalyzed by FeNPs.

Scheme 17. Plusible mechanism for the synthesis of quinoxalines using by FeNPs.

Scheme 18. Synthesis of quinoxalines derivatives in the presence of Cu(ii)-Schiff base/SBA-15.

Scheme 19. Plausible mechanism for the synthesis of quinoxalines using Cu(ii)-Schiff base/SBA-15.

Scheme 20. Cu–Al-2 catalyzed synthesis of quinoxalines.

Scheme 21. An efficient synthesis of benzoheterocycles using CuO nanoparticle.

Scheme 22. Synthesis of quinoxalines using g-C₃N₄/Cu₃TiO₄ (CNCT).

Scheme 23. Plausible mechanism for the synthesis of quinoxalines using CNCT.

Scheme 24. Ni(ii) ion loaded Y-type zeolite catalyzed synthesis of quinoxalines.

Scheme 25. Synthesis of quinoxalines using Ni catalyst.

Scheme 26. One-pot synthesis of quinoxaline derivatives using Au/CeO₂.

Scheme 27. Synthesis of benzimidazoylquinoxaline using Au/CeO₂ catalyst.

Scheme 28. Syntheses of aryl 1,2-diketones and quinoxaline derivative using AuNPS.

Scheme 29. Syntheses of quinoxaline derivatives using SiO₂ nanoparticles.

Scheme 30. The proposed mechanism for the synthesis of quinoxalines using silica NPs.

Scheme 31. Nano-BF₃ SiO₂ catalyzed the synthesis of quinoxalines.

Scheme 32. Synthesis of quinoxalines using tungstophosphoric acid immobilized on mesoporous silica nanoparticles (SNPX#WPA).

Scheme 33. Plausible mechanism for the synthesis of quinoxalines using tungstophosphoric acid immobilized on mesoporous silica nanoparticles (SNPX#WPA).

Scheme 34. Synthesis of quinoxalines using SiO₂-GO as a catalyst.

Scheme 35. TiO₂ catalyzed synthesis of quinoxalines.

Scheme 36. Application of TiO₂–P25–SO₄ for the synthesis of quinoxalines.

Scheme 37. The synthesis of quinoxalines using nano ZrO₂.

Scheme 38. The ZrOL₂@SMNP catalyzed synthesis of quinoxalines. The black sphere surrounded by white layer represents starch-coated Fe₂O₃.

Scheme 39. The synthesis of quinoxalines using nanosulfated zirconia, nano-structured ZnO, nano-γ-alumina and nano-ZSM-5 zeolites.

Scheme 40. Plausible mechanism for the synthesis of quinoxalines using catalysts (nanosulfated zirconia, nano-structured ZnO, nano-γ-alumina and nano-ZSM-5 zeolites).

Scheme 41. The synthesis of quinoxalines using Co-phen/C-800.

Scheme 42. Ni@Co₃O₄ (Co₃O₄ nanocages decorated with nickel nanoparticles) for the synthesis of quinoxalines.

Scheme 43. The synthesis of quinoxalines using Co nanoparticle.

Scheme 44. Nano-MoO₃ catalysed synthesis of quinoxalines.

Scheme 45. Synthesis of quinoxalines using keplerate {Mo132} nanoball.

Scheme 46. Application carbon-doped MoO₃–TiO₂ (CMT) for the synthesis of quinoxalines.

Scheme 47. Synthesis of quinoxalines using manganese oxide (MnO) nanocrystals.

Scheme 48. MnFe₂O₄ catalyzed synthesis of quinoxalines.

Scheme 49. Synthesis of quinoxalines using Ru complex supported on graphene oxide.

Scheme 50. Application of Ru NPs for the synthesis of quinoxalines.

Scheme 51. ZnO-loaded mesoporous silica (KIT-6) as an efficient solid catalyst for synthesis of quinoxalines and its plausible mechanism.

Scheme 52. Synthesis of quinoxaline derivatives catalyzed by Pd/SBA-15.

Scheme 53. Na₂PdP₂O₇ as an efficient catalyst for synthesis of quinoxalines and its plausible mechanism.

Scheme 54. Synthesis of quinoxalines using Cs(CTA)₂ PW₁₂O₄₀ as a catalyst.

Scheme 55. Synthesis of quinoxalines in the presence of 10 wt% TPA/MCM-41 at room temperature in EtOH.

Rangappa S. Keri

Dinesh Reddy

Srinivasa Budagumpi

Vinayak Adimule