Efficient and Environmentally Sustainable Heterogeneous Polystyrene Divinylbenzene-Supported Sulphanilic Acid Catalyst for the Synthesis of Imidazopyridine Derivatives

Authors

  • Sunil B Hiwale Department of Chemistry, Sant Ramdas Arts, Commerce & Science College, Ghansawangi, Dist. Jalna, Maharashtra, India Author

DOI:

https://doi.org/10.32628/IJSRST2511146

Keywords:

imidazo[1,2-a]pyridine, multicomponent reaction, polymer-supported acid, polystyrene–divinylbenzene, sulphanilic acid, green chemistry

Abstract

We report a recyclable Brønsted-acid catalyst consisting of sulphanilic acid covalently immobilized on a cross-linked polystyrene–divinylbenzene matrix (PS–DVB–SA). The material promotes the solvent-free two-component creation of imidazo[1,2-a]pyridines from 2-aminopyridines, aldehydes, and isocyanides at 80 °C, delivering products in 81–93% isolated yields within 27–79 min. Comprehensive characterization (FT-IR, 1H NMR and 13C NMR) confirms functional groups and presence of attachment of H-atom and C-atom environment. The catalyst is magnet-free, easy to filter, and reusability of catalyst done for at least five cycles without considerable loss. This work unites the known pharmacological relevance of imidazo[1,2-a]pyridines and the powerful Groebke–Blackburn–Bienaymé (GBB) multicomponent logic with a robust, industry-familiar PS-DVB platform, offering a practical route to scalable, low-waste heterocycle synthesis.

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References

Devi N, Singh D, Rawal RK, Bariwal J, Singh V. Medicinal Attributes of Imidazo[1,2-a]pyridine Derivatives: An Update. Curr Top Med Chem. 2016;16(26):2963-2994. DOI: https://doi.org/10.2174/1568026616666160506145539

Sharma, M., & Prasher, P. (2022). C2-functionalized imidazo[1,2-a]pyridine: Synthesis and medicinal relevance. Synthetic Communications, 52(11–12), 1337–1356. DOI: https://doi.org/10.1080/00397911.2022.2079091

Boltjes, A. and Dömling, A. (2019), The Groebke-Blackburn-Bienaymé Reaction. Eur. J. Org. Chem., 2019: 7007-7049. DOI: https://doi.org/10.1002/ejoc.201901124

Martini, C., Mardjan, M. I. D., & Basso, A. (2024). The Groebke–Blackburn–Bienaymé reaction in its maturity: innovation and improvements since its 21st birthday (2019–2023). Beilstein Journal of Organic Chemistry, 20(1), 1839-1879. DOI: https://doi.org/10.3762/bjoc.20.162

Couty, F., Evano, G., Katritzky, A. R., Ramsden, C. A., Scriven, E. F. V., & Taylor, R. J. K. (2008). Comprehensive heterocyclic chemistry III. Katritzky AR, Ramsden CA, Scriven EFV, Taylor RJK (eds), 11, 409-499.

Enguehard-Gueiffier, C., & Gueiffier, A. (2007). Recent Progress in the Pharmacology of Imidazo [1, 2-a] pyridines. Mini Reviews in Medicinal Chemistry, 7(9), 888-899. DOI: https://doi.org/10.2174/138955707781662645

Feng, Song, Di Hong, Baoxia Wang, Xiufang Zheng, Kun Miao, Lisha Wang, Hongying Yun, Lu Gao, Shuhai Zhao, and Hong C. Shen. "Discovery of imidazopyridine derivatives as highly potent respiratory syncytial virus fusion inhibitors." ACS Medicinal Chemistry Letters 6, no. 3 (2015): 359-362. DOI: https://doi.org/10.1021/acsmedchemlett.5b00008

Kamal, A., Kumar, G. B., Nayak, V. L., Reddy, V. S., Shaik, A. B., & Reddy, M. K. (2015). Design, synthesis and biological evaluation of imidazopyridine/imidazopyrimidine-benzimidazole conjugates as potential anticancer agents. MedChemComm, 6(4), 606-612. DOI: https://doi.org/10.1039/C4MD00400K

Rival, Y., Grassy, G., & Michel, G. (1992). Synthesis and antibacterial activity of some Imidazo [1, 2-α] pyrimidine derivatives. Chemical and pharmaceutical bulletin, 40(5), 1170-1176. DOI: https://doi.org/10.1248/cpb.40.1170

Almirante, Luigi, Luigi Polo, Alfonso Mugnaini, Ercolina Provinciali, Pierluigi Rugarli, Adriana Biancotti, Afro Gamba, and Walter Murmann. "Derivatives of imidazole. I. Synthesis and reactions of imidazo [1, 2-α] pyridines with analgesic, antiinflammatory, antipyretic, and anticonvulsant activity." Journal of medicinal chemistry 8, no. 3 (1965): 305-312. DOI: https://doi.org/10.1021/jm00327a007

Gudmundsson, K. S., Williams, J. D., Drach, J. C., & Townsend, L. B. (2003). Synthesis and antiviral activity of novel erythrofuranosyl imidazo [1, 2-a] pyridine C-nucleosides constructed via palladium coupling of iodoimidazo [1, 2-a] pyridines and dihydrofuran. Journal of medicinal chemistry, 46(8), 1449-1455. DOI: https://doi.org/10.1021/jm020339r

Puerstinger, G., Paeshuyse, J., De Clercq, E., & Neyts, J. (2007). Antiviral 2, 5-disubstituted imidazo [4, 5-c] pyridines: From anti-pestivirus to anti-hepatitis C virus activity. Bioorganic & medicinal chemistry letters, 17(2), 390-393. DOI: https://doi.org/10.1016/j.bmcl.2006.10.039

Liu, Rui, Kate Marshall, Rui Ma, Kim Lien Thi Pham, Gauri Shetye, Zhihao Liu, Sanghyun Cho et al. "Syntheses and studies of deuterated Imdiazo [1, 2-a] pyridine-3-carboxamides with potent anti-tuberculosis activity and improved metabolic properties." Bioorganic chemistry 128 (2022): 106074. DOI: https://doi.org/10.1016/j.bioorg.2022.106074

Wang, Hongjian, Apeng Wang, Jian Gu, Lei Fu, Kai Lv, Chao Ma, Zeyu Tao et al. "Synthesis and antitubercular evaluation of reduced lipophilic imidazo [1, 2-a] pyridine-3-carboxamide derivatives." European Journal of Medicinal Chemistry 165 (2019): 11-17. DOI: https://doi.org/10.1016/j.ejmech.2018.12.071

Serrano-Contreras, J. I., Meléndez-Camargo, M. E., Márquez-Flores, Y. K., Soria-Serrano, M. P., & Campos-Aldrete, M. E. (2022). Exploratory toxicology studies of 2, 3-substituted imidazo [1, 2-a] pyridines with antiparasitic and anti-inflammatory properties. Toxicology Research, 11(5), 730-742. DOI: https://doi.org/10.1093/toxres/tfac046

N'Guessan, Jean-Paul Déto Ursul, Pierre-Olivier Delaye, Mélanie Pénichon, Claude L. Charvet, Cédric Neveu, Mahama Ouattara, Cécile Enguehard-Gueiffier, Alain Gueiffier, and Hassan Allouchi. "Discovery of imidazo [1, 2-a] pyridine-based anthelmintic targeting cholinergic receptors of Haemonchus contortus." Bioorganic & Medicinal Chemistry 25, no. 24 (2017): 6695-6706. DOI: https://doi.org/10.1016/j.bmc.2017.11.012

Nandhagopal, M., Mala, R., Somarathinam, K., Dhakshinamurthy, D., Narayanasamy, M., Vijayan, P., & Shankar, M. M. (2024). Anti-fungal effects of novel N-(tert-butyl)-2-(pyridin-2-yl)imidazo[1,2-a]pyridin-3-amine derivative and it's in-vitro, in-silico, and mode of action against Candida spp. Archives of microbiology, 206(4), 186. DOI: https://doi.org/10.1007/s00203-023-03780-w

Abdel-Shafi, A. A., Fathi, A. M., Ismail, M. A., & Boykin, D. W. (2017). Antiprotozoal agents as water soluble singlet oxygen photosensitizers: Imidazo [1, 2-a] pyridine and 5, 6, 7, 8-tetrahydro-imidazo [1, 2-a] pyridine derivatives. Journal of Luminescence, 181, 164-170. DOI: https://doi.org/10.1016/j.jlumin.2016.09.021

Guzel, Y., & Kopar, A. K. (2002). Investigation of Antiulcer Activities of Imidazo [1, 2‐6alpha;] pyridinyl‐2‐alkylaminobenzoxazoles and 5, 6, 7, 8‐Tetahydroimidazo [1, 2‐alpha;] pyridinylbenzoxazoles with Electron‐Topological (ET) Method. Archiv der Pharmazie: An International Journal Pharmaceutical and Medicinal Chemistry, 335(1), 27-32. DOI: https://doi.org/10.1002/1521-4184(200201)335:1<27::AID-ARDP27>3.0.CO;2-V

Ulloora, S., Adhikari, A. V., & Shabaraya, R. (2013). Synthesis and antiepileptic studies of new imidazo [1, 2-a] pyridine derivatives. Chinese Chemical Letters, 24(9), 853-856. DOI: https://doi.org/10.1016/j.cclet.2013.05.030

Baviskar, Ashish T., Chetna Madaan, Ranjan Preet, Purusottam Mohapatra, Vaibhav Jain, Amit Agarwal, Sankar K. Guchhait, Chanakya N. Kundu, Uttam C. Banerjee, and Prasad V. Bharatam. "N-fused imidazoles as novel anticancer agents that inhibit catalytic activity of topoisomerase IIα and induce apoptosis in G1/S phase." Journal of medicinal chemistry 54, no. 14 (2011): 5013-5030. DOI: https://doi.org/10.1021/jm200235u

Byth, K. F., Culshaw, J. D., Green, S., Oakes, S. E., & Thomas, A. P. (2004). Imidazo [1, 2-a] pyridines. Part 2: SAR and optimisation of a potent and selective class of cyclin-dependent kinase inhibitors. Bioorganic & medicinal chemistry letters, 14(9), 2245-2248. DOI: https://doi.org/10.1016/j.bmcl.2004.02.015

Haghighijoo, Zahra, Sara Akrami, Mina Saeedi, Afsaneh Zonouzi, Aida Iraji, Bagher Larijani, Hossein Fakherzadeh et al. "N-Cyclohexylimidazo [1, 2-a] pyridine derivatives as multi-target-directed ligands for treatment of Alzheimer's disease." Bioorganic Chemistry 103 (2020): 104146. DOI: https://doi.org/10.1016/j.bioorg.2020.104146

Humphries, A. C., Gancia, E., Gilligan, M. T., Goodacre, S., Hallett, D., Merchant, K. J., & Thomas, S. R. (2006). 8-Fluoroimidazo [1, 2-a] pyridine: Synthesis, physicochemical properties and evaluation as a bioisosteric replacement for imidazo [1, 2-a] pyrimidine in an allosteric modulator ligand of the GABAA receptor. Bioorganic & medicinal chemistry letters, 16(6), 1518-1522. DOI: https://doi.org/10.1016/j.bmcl.2005.12.037

Marcinkowska, Monika, Marcin Kołaczkowski, Krzysztof Kamiński, Adam Bucki, Maciej Pawłowski, Agata Siwek, Tadeusz Karcz et al. "Design, synthesis, and biological evaluation of fluorinated imidazo [1, 2-a] pyridine derivatives with potential antipsychotic activity." European Journal of Medicinal Chemistry 124 (2016): 456-467. DOI: https://doi.org/10.1016/j.ejmech.2016.08.059

Zheng, X., Wang, C., Zhai, N., Luo, X., Liu, G., & Ju, X. (2021). In silico screening of novel α1-GABAA receptor PAMs towards schizophrenia based on combined modeling studies of imidazo [1, 2-a]-pyridines. International Journal of Molecular Sciences, 22(17), 9645. DOI: https://doi.org/10.3390/ijms22179645

Gaikwad, S. S., Thorat, N. M., & Patil, L. R. (2021). Sonication Assisted One-Pot Synthesis of Substituted Imidazopyridine from Styrene in Water. Current Organic Synthesis, 18(4), 366-370. DOI: https://doi.org/10.2174/1570179417999201105160447

Jadhao, A., Zyate, S., & Gaikwad, S. (2024). Blue LED-driven CN bond formation for synthesis of imidazopyridines. Indian Journal of Chemistry (IJC), 63(2), 203-210. DOI: https://doi.org/10.56042/ijc.v63i2.6338

Gaikwad, S. S., Hiwale, M. M., Zyate, S. C., Gaikwad, S. B., Waghmode, S. B., & Jadhao, A. R. (2025). Laccase Mediated One-Pot, Green Synthesis of Thiazoles, β-Keto Sulfones and Imidazopyridines. Applied Biochemistry and Biotechnology, 197(4), 2757-2767.27. DOI: https://doi.org/10.1007/s12010-024-05157-1

Gaikwad, S. S., Nimal, S. K., Pol, R., Markad, D., Jadhao, A. R., Jadhav, U., ... & Chikate, R. C. (2023). Targeting AKT2 in MDA‐MB‐231 Cells by Pyrazole Hybrids: Structural, Biological and Molecular Docking Studies. Chemistry & Biodiversity, 20(11), e202300799. DOI: https://doi.org/10.1002/cbdv.202300799

Gaikwad, S. B., & Puri, K. (2024). MnFe2O4 nanoparticle as a new and magnetically separable nanocatalyst for solvent-free synthesis of dihydropyrano [2, 3-c] pyrazole derivatives. International Journal of Scientific Research in Science and Technology, 11(4), 318-326. DOI: https://doi.org/10.32628/IJSRST173876

Gaikwad, S. B., Borul, S. B., & Bembalkar, S. R. (2015). Synthesis of Bis 1h-Indole Methane Derivatives Using Cellulose Perchloric Acid Under Solvent-Free Conditions. International Journal of Chemical and Physical Sciences, 4(6), 62-65.

Bhakare, S. D., Gaikwad, S. B., & Jogdand, R. B. (2016). Bismuth triflate catalyzed ecofriendly and efficient synthesis of bis (indolyl) methanes by grinding approach. Heterocycl. Lett, 6, 421-425.

Patel, S., Yaduwanshi, P. S., Jain, A., Singh, V. R., & Jain, S. (2025). Exploring Synthesis and Functionalization of Imidazo [1, 2˗ a] pyridines: A Promising Heterocyclic Framework. Current Organic Chemistry. References cited therein

Adam, F., Hello, K. M., & Ali, T. H. (2011). Solvent free liquid-phase alkylation of phenol over solid sulfanilic acid catalyst. Applied Catalysis A: General, 399(1-2), 42-49. DOI: https://doi.org/10.1016/j.apcata.2011.03.039

Alghamdi, A. A., Mrair, Y. M., Alharthi, F. A., & Al-Odayni, A.-B. (2020). Catalytic Performance of SBA-15-Supported Poly (Styrenesulfonic Acid) in the Esterification of Acetic Acid with n-Heptanol. Applied Sciences, 10(17), 5835. DOI: https://doi.org/10.3390/app10175835

Hiwale, S. B. (2025). Synthesis of bis (indolyl) methanes Using Environmentally Favorable Cellulose Supported Sulfanilic Acid Catalyst. International Journal of Scientific Research in Science and Technology, 12(4), 196-199. DOI: https://doi.org/10.32628/IJSRST251281

Patel, J. P., Avalani, J. R., & Raval, D. K. (2013). Polymer supported sulphanilic acid: A highly efficient and recyclable green heterogeneous catalyst for the construction of 4, 5-dihydropyrano [3, 2-c] chromenes under solvent-free conditions. Journal of Chemical Sciences, 125(3), 531-536. DOI: https://doi.org/10.1007/s12039-013-0408-8

Krishnamoorthy, R., & Anaikutti, P. (2023). Iodine catalyzed synthesis of imidazo [1, 2-a] pyrazine and imidazo [1, 2-a] pyridine derivatives and their anticancer activity. RSC advances, 13(51), 36439-36454. DOI: https://doi.org/10.1039/D3RA07842F

Rousseau, A. L., Matlaba, P., & Parkinson, C. J. (2007). Multicomponent synthesis of imidazo [1, 2-a] pyridines using catalytic zinc chloride. Tetrahedron letters, 48(23), 4079-4082. DOI: https://doi.org/10.1016/j.tetlet.2007.04.008

Martinho, L. A., & Andrade, C. K. Z. (2024). HPW-Catalyzed environmentally benign approach to imidazo [1, 2-a] pyridines. Beilstein Journal of Organic Chemistry, 20(1), 628-637. DOI: https://doi.org/10.3762/bjoc.20.55

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Published

27-02-2025

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Section

Research Articles

How to Cite

[1]
Sunil B Hiwale, Tran., “Efficient and Environmentally Sustainable Heterogeneous Polystyrene Divinylbenzene-Supported Sulphanilic Acid Catalyst for the Synthesis of Imidazopyridine Derivatives”, Int J Sci Res Sci & Technol, vol. 12, no. 1, pp. 844–853, Feb. 2025, doi: 10.32628/IJSRST2511146.