Multicomponent reactions (MCRs) represent an efficient and versatile approach in organic synthesis, enabling the formation of complex molecules through a single, one-pot procedure. This methodology is particularly advantageous for the synthesis of heterocyclic compounds that are prevalent in numerous biologically active molecules and pharmaceuticals. The one-pot nature of MCRs allows for the simultaneous combination of three or more reactants, leading to high atom economy, reduced reaction times, and minimized purification steps. This abstract explores the principles and applications of one-pot MCRs in the synthesis of various heterocyclic frameworks, highlighting recent advancements and key strategies employed to enhance reaction efficiency and selectivity. Through representative examples, we demonstrate how MCRs can be utilized to construct a diverse array of heterocycles, including pyridines, pyrimidines, imidazoles, and oxazoles, under mild and environmentally benign conditions. The potential of one-pot MCRs to streamline the synthesis of complex heterocyclic architectures positions them as a powerful tool in modern synthetic organic chemistry.

🔒 This is a subscription article

Full text is available to subscribers and institutional members. Please choose an option below to access it.

1. Yin, Y., Liu, S., Yang, Y., Gong, D., Liu, M., Liu, G., Wu, P., Xu, Q., Yu, C., & Zeng, G. (2023). Polyethyleneimine–polyvinylchloride-based crosslinked membranes for use in PEM water electrolysis operating above 100 °C. International Journal of Hydrogen Energy, 48(1), 24–34.

2. Sharma, P. P., Gupta, H., & Kulshrestha, V. (2020). Phosphorylated hybrid silica–sulfonated polyethersulfone composite proton-exchange membranes: Magnetic resonance investigation for enhanced proton-exchange dynamics. International Journal of Hydrogen Energy, 45(34), 16955–16964.

3. Siracusano, S., Baglio, V., Nicotera, I., Mazzapioda, L., Aricò, A. S., Panero, S., & Navarra, M. A. (2017). Sulfated titania as additive in Nafion membranes for water electrolysis applications. International Journal of Hydrogen Energy, 42(46), 27851–27858.

4. da Costa, E. P., Coelho, S. E., de Oliveira, A. H., Araújo, R. M., Cavalcanti, L. N., Domingos, J. B., & Menezes, F. G. (2018). Multicomponent synthesis of substituted 3-styryl-1H-quinoxalin-2-ones in an aqueous medium. Tetrahedron Letters, 59(44), 3961–3964.

5. Reddy, M. S., Chowhan, L. R., Kumar, N. S., Ramesh, P., & Mukkamala, S. B. (2018). An expedient regio- and diastereoselective synthesis of novel spiropyrrolidinylindenoquinoxalines via 1,3-dipolar cycloaddition reaction. Tetrahedron Letters, 59(14), 1366–1371.

6. Farooq, S., & Ngaini, Z. (2021). Chalcone-derived benzoheterodiazepines for medicinal applications: A two-pot and one-pot synthetic approach. Journal of Heterocyclic Chemistry, 58(10), 1914–1928.

7. Thakur, A., Verma, M., Setia, P., Bharti, R., Sharma, R., Sharma, A., Negi, N. P., Anand, V., & Bansal, R. (2023). DFT analysis and in vitro studies of isoxazole derivatives as potent antioxidant and antibacterial agents synthesized via one-pot methodology. Research on Chemical Intermediates, 49(3), 859–883.

8. Teli, S., Teli, P., Soni, S., Sahiba, N., & Agarwal, S. (2023). Synthetic aspects of 1,4- and 1,5-benzodiazepines using o-phenylenediamine: A study of the past quinquennial. RSC Advances, 13(6), 3694–3714.

9. Thakral, A., Verma, M., Thakur, A., Bharti, R., & Sharma, R. (2024). Comprehensive review on one-pot green synthesis of pyran and chromene fused benzo[α]phenazines. Polycyclic Aromatic Compounds, 44(3), 1697–1721.

10. Thakur, A., Verma, M., Setia, P., Bharti, R., Sharma, R., Sharma, A., Negi, N. P., Anand, V., & Bansal, R. (2023). DFT analysis and in vitro studies of isoxazole derivatives as potent antioxidant and antibacterial agents synthesized via one-pot methodology. Research on Chemical Intermediates, 49(3), 859–883. [Duplicate of Ref. 7]

11. Indalkar, K. S., Patil, M. S., & Chaturbhuj, G. U. (2017). An efficient, environmentally benign, and solvent-free protocol for the synthesis of 4-substituted 1,5-benzodiazepines catalyzed by reusable sulfated polyborate. Tetrahedron Letters, 58(48), 4496–4502.

12. da Costa, E. P., Coelho, S. E., de Oliveira, A. H., Araújo, R. M., Cavalcanti, L. N., Domingos, J. B., & Menezes, F. G. (2018). Multicomponent synthesis of substituted 3-styryl-1H-quinoxalin-2-ones in an aqueous medium. Tetrahedron Letters, 59(44), 3961–3964. [Duplicate of Ref. 4]

13. Reddy, M. S., Chowhan, L. R., Kumar, N. S., Ramesh, P., & Mukkamala, S. B. (2018). An expedient regio- and diastereoselective synthesis of novel spiropyrrolidinylindenoquinoxalines via 1,3-dipolar cycloaddition reaction. Tetrahedron Letters, 59(14), 1366–1371. [Duplicate of Ref. 5]

14. Shaabani, A., Hooshmand, S. E., Nazeri, M. T., Afshari, R., & Ghasemi, S. (2016). Deep eutectic solvent as a highly efficient reaction medium for the one-pot synthesis of benzo-fused seven-membered heterocycles. Tetrahedron Letters, 57(33), 3727–3730.

15. Zhong, R., Lindhorst, A. C., Groche, F. J., & Kühn, F. E. (2017). Immobilization of N-heterocyclic carbene compounds: A synthetic perspective. Chemical Reviews, 117(3), 1970–2058.

16. Sharghi, H., Shiri, P., & Aberi, M. (2017). Five-membered N-heterocycles synthesis catalyzed by nano-silica-supported copper(II)–2-imino-1,2-diphenylethan-1-ol complex. Catalysis Letters, 147, 2844–2862.

17. Salehpour, M., Azizian, J., & Kefayati, H. (2017). Clean synthesis of novel spiro[indene-2,2′-[1,3,5]-oxathiazine]-1,3-diones in water. Chinese Chemical Letters, 28(5), 1079–1082.

Multicomponent reactions (MCRs) represent an efficient and versatile approach in organic synthesis, enabling the formation of complex molecules through a single, one-pot procedure. This methodology is particularly advantageous for the synthesis of heterocyclic compounds that are prevalent in numerous biologically active molecules and pharmaceuticals. The one-pot nature of MCRs allows for the simultaneous combination of three or more reactants, leading to high atom economy, reduced reaction times, and minimized purification steps. This abstract explores the principles and applications of one-pot MCRs in the synthesis of various heterocyclic frameworks, highlighting recent advancements and key strategies employed to enhance reaction efficiency and selectivity. Through representative examples, we demonstrate how MCRs can be utilized to construct a diverse array of heterocycles, including pyridines, pyrimidines, imidazoles, and oxazoles, under mild and environmentally benign conditions. The potential of one-pot MCRs to streamline the synthesis of complex heterocyclic architectures positions them as a powerful tool in modern synthetic organic chemistry.

🔒 This is a subscription article

Full text is available to subscribers and institutional members. Please choose an option below to access it.

1. Yin, Y., Liu, S., Yang, Y., Gong, D., Liu, M., Liu, G., Wu, P., Xu, Q., Yu, C., & Zeng, G. (2023). Polyethyleneimine–polyvinylchloride-based crosslinked membranes for use in PEM water electrolysis operating above 100 °C. International Journal of Hydrogen Energy, 48(1), 24–34.

2. Sharma, P. P., Gupta, H., & Kulshrestha, V. (2020). Phosphorylated hybrid silica–sulfonated polyethersulfone composite proton-exchange membranes: Magnetic resonance investigation for enhanced proton-exchange dynamics. International Journal of Hydrogen Energy, 45(34), 16955–16964.

3. Siracusano, S., Baglio, V., Nicotera, I., Mazzapioda, L., Aricò, A. S., Panero, S., & Navarra, M. A. (2017). Sulfated titania as additive in Nafion membranes for water electrolysis applications. International Journal of Hydrogen Energy, 42(46), 27851–27858.

4. da Costa, E. P., Coelho, S. E., de Oliveira, A. H., Araújo, R. M., Cavalcanti, L. N., Domingos, J. B., & Menezes, F. G. (2018). Multicomponent synthesis of substituted 3-styryl-1H-quinoxalin-2-ones in an aqueous medium. Tetrahedron Letters, 59(44), 3961–3964.

5. Reddy, M. S., Chowhan, L. R., Kumar, N. S., Ramesh, P., & Mukkamala, S. B. (2018). An expedient regio- and diastereoselective synthesis of novel spiropyrrolidinylindenoquinoxalines via 1,3-dipolar cycloaddition reaction. Tetrahedron Letters, 59(14), 1366–1371.

6. Farooq, S., & Ngaini, Z. (2021). Chalcone-derived benzoheterodiazepines for medicinal applications: A two-pot and one-pot synthetic approach. Journal of Heterocyclic Chemistry, 58(10), 1914–1928.

7. Thakur, A., Verma, M., Setia, P., Bharti, R., Sharma, R., Sharma, A., Negi, N. P., Anand, V., & Bansal, R. (2023). DFT analysis and in vitro studies of isoxazole derivatives as potent antioxidant and antibacterial agents synthesized via one-pot methodology. Research on Chemical Intermediates, 49(3), 859–883.

8. Teli, S., Teli, P., Soni, S., Sahiba, N., & Agarwal, S. (2023). Synthetic aspects of 1,4- and 1,5-benzodiazepines using o-phenylenediamine: A study of the past quinquennial. RSC Advances, 13(6), 3694–3714.

9. Thakral, A., Verma, M., Thakur, A., Bharti, R., & Sharma, R. (2024). Comprehensive review on one-pot green synthesis of pyran and chromene fused benzo[α]phenazines. Polycyclic Aromatic Compounds, 44(3), 1697–1721.

10. Thakur, A., Verma, M., Setia, P., Bharti, R., Sharma, R., Sharma, A., Negi, N. P., Anand, V., & Bansal, R. (2023). DFT analysis and in vitro studies of isoxazole derivatives as potent antioxidant and antibacterial agents synthesized via one-pot methodology. Research on Chemical Intermediates, 49(3), 859–883. [Duplicate of Ref. 7]

11. Indalkar, K. S., Patil, M. S., & Chaturbhuj, G. U. (2017). An efficient, environmentally benign, and solvent-free protocol for the synthesis of 4-substituted 1,5-benzodiazepines catalyzed by reusable sulfated polyborate. Tetrahedron Letters, 58(48), 4496–4502.

12. da Costa, E. P., Coelho, S. E., de Oliveira, A. H., Araújo, R. M., Cavalcanti, L. N., Domingos, J. B., & Menezes, F. G. (2018). Multicomponent synthesis of substituted 3-styryl-1H-quinoxalin-2-ones in an aqueous medium. Tetrahedron Letters, 59(44), 3961–3964. [Duplicate of Ref. 4]

13. Reddy, M. S., Chowhan, L. R., Kumar, N. S., Ramesh, P., & Mukkamala, S. B. (2018). An expedient regio- and diastereoselective synthesis of novel spiropyrrolidinylindenoquinoxalines via 1,3-dipolar cycloaddition reaction. Tetrahedron Letters, 59(14), 1366–1371. [Duplicate of Ref. 5]

14. Shaabani, A., Hooshmand, S. E., Nazeri, M. T., Afshari, R., & Ghasemi, S. (2016). Deep eutectic solvent as a highly efficient reaction medium for the one-pot synthesis of benzo-fused seven-membered heterocycles. Tetrahedron Letters, 57(33), 3727–3730.

15. Zhong, R., Lindhorst, A. C., Groche, F. J., & Kühn, F. E. (2017). Immobilization of N-heterocyclic carbene compounds: A synthetic perspective. Chemical Reviews, 117(3), 1970–2058.

16. Sharghi, H., Shiri, P., & Aberi, M. (2017). Five-membered N-heterocycles synthesis catalyzed by nano-silica-supported copper(II)–2-imino-1,2-diphenylethan-1-ol complex. Catalysis Letters, 147, 2844–2862.

17. Salehpour, M., Azizian, J., & Kefayati, H. (2017). Clean synthesis of novel spiro[indene-2,2′-[1,3,5]-oxathiazine]-1,3-diones in water. Chinese Chemical Letters, 28(5), 1079–1082.