American Journal of Heterocyclic Chemistry

Submit a Manuscript

Publishing with us to make your research visible to the widest possible audience.

Propose a Special Issue

Building a community of authors and readers to discuss the latest research and develop new ideas.

Deep Eutectic Solvent a Highly Efficient Medium for the Synthesis of Imidazo [1, 2-a] Pyridines Having Green Chemistry Approach

The imidazo [1, 2-a] pyridine is valuable structural unit in the area of natural products and pharmaceuticals. Extremely effective one pot method developed for the production of imidazo [1, 2-a] pyridines. The reaction of N-bromosuccinimide, acetophenones and 2-aminopyridines in deep eutectic solvent and reaction completed within a minute. The most remarkable features of such reaction is lowest minimum time, high atom, mild reaction condition and step economy. Methods The mixture of substituted acetophenones, N-bromosuccinimide in deep eutectic solvent as a green medium and 2-aminopyridines. The optimization of the reaction conditions with regard to their chemo selectivity of deep eutectic solvent. An imidazopyridine is a nitrogen containing heterocycle which plays crucial role in medicinal and pharmacological chemistry. Results To synthesize the imidazo [1, 2-a] pyridines, In the deep eutectic solvents add N-bromosuccinimide, acetophenones at room temperature immediately reaction completed within a minute, TLC Shows single spot which indicate that formation of α- bromoketones. On formation of α- bromoketones; 2-aminopyridine was added in the reaction mass after completion of reaction, the reaction mixture was poured in ice-cold water; the solid product obtained was filtered. Conclusion The main remarkable characteristics of this protocol such as no need to isolate lachrymatric α-bromoketones, clean reaction profile, mild reaction condition, require minimum reaction time, inexpensive and green aspects such as avoid hazardous solvents, poisonous catalyst, higher yield and ease of work-up.

Deep Eutectic Solvent, Imidazol-Pyridine, Acetophenones, 2-Aminopyridines

APA Style

Majid Shaikh, Sayyad Sultan Kasim. (2022). Deep Eutectic Solvent a Highly Efficient Medium for the Synthesis of Imidazo [1, 2-a] Pyridines Having Green Chemistry Approach. American Journal of Heterocyclic Chemistry, 8(1), 7-11.

ACS Style

Majid Shaikh; Sayyad Sultan Kasim. Deep Eutectic Solvent a Highly Efficient Medium for the Synthesis of Imidazo [1, 2-a] Pyridines Having Green Chemistry Approach. Am. J. Heterocycl. Chem. 2022, 8(1), 7-11. doi: 10.11648/j.ajhc.20220801.12

AMA Style

Majid Shaikh, Sayyad Sultan Kasim. Deep Eutectic Solvent a Highly Efficient Medium for the Synthesis of Imidazo [1, 2-a] Pyridines Having Green Chemistry Approach. Am J Heterocycl Chem. 2022;8(1):7-11. doi: 10.11648/j.ajhc.20220801.12

Copyright © 2022 Authors retain the copyright of this article.
This article is an open access article distributed under the Creative Commons Attribution License ( which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

1. Almirante, L., Polo, L., Mugnaini, A., Provinciali, E., Rugarli, P., Biancotti, A., Gamba, A. and Murmann, W. Derivatives of imidazole. I. Journal of medicinal chemistry, 1965, 8 (3), pp. 305-312.
2. Hemasrilatha, S., Sruthi, K., Manjula, A., Babu, V. H. and Rao, B. V. Synthesis and anti-inflammatory activity of imidazo [1, 2-a] pyridinyl/pyrazinyl benzamides and acetamides. Indian Journal of Chemistry, Vol. 51B, July 2012, pp 981-987.
3. Dymińska, L., 2015. Imidazopyridines as a source of biological activity and their pharmacological potentials—infrared and Raman spectroscopic evidence of their content in pharmaceuticals and plant materials. Bioorganic & Medicinal Chemistry, 23 (18), pp. 6087-6099.
4. Gaba, M. and Mohan, C., 2016. Development of drugs based on imidazole and benzimidazole bioactive heterocycles: recent advances and future directions. Medicinal Chemistry Research, 25 (2), pp. 173-210. Zhao, C., Li, F., Yang, S., Liu, L., Huang, Z. and Chai, H. Heterocyclic Compounds, 201`8, 54 (5), pp. 568-571.
5. Ebenezer, O., Jordaan, M. A., Carena, G., Bono, T., Shapi, M. and Tuszynski, J. A., 2022. An Overview of the Biological Evaluation of Selected Nitrogen-Containing Heterocycle Medicinal Chemistry Compounds. International Journal of Molecular Sciences, 23 (15), p. 8117.
6. Enguehard-Gueiffier, C. and Gueiffier, A., 2007. Recent Progress in the Pharmacology of Imidazo [1, 2-a] pyridines. Mini Reviews in Medicinal Chemistry, 7 (9), pp. 888-899.
7. Lin, X., Kang, D., Li, X., Zhan, P., Liu, X. and Zhang, Q., 2014. Discovery and characterization of novel imidazopyridine derivative CHEQ-2 as a potent CDC25 inhibitor and promising anticancer drug candidate. European journal of medicinal chemistry, 82, pp. 293-307.
8. LS Kishbaugh, T. Pyridines and Imidazopyridines with medicinal significance. Current topics in medicinal chemistry, 2016, 16 (28), pp. 3274-3302.
9. Bagdi, A. K., Santra, S., Monir, K. and Hajra, A., 2015. Synthesis of imidazo [1, 2-a] pyridines: a decade update. Chemical Communications, 51 (9), pp. 1555-1575.
10. Gudmundsson, K. S., Williams, J. D., Drach, J. C. and 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), pp. 1449-1455.
11. Sivappa, R., Sammeta, V. R., Huang, Y., Golen, J. A. and Savinov, S. N., 2019. Facile synthesis of 3-substituted imidazo [1, 2-a] pyridines through formimidamide chemistry. RSC advances, 9 (51), pp. 29659-29664.
12. López-Martínez, M., Salgado-Zamora, H., Campos-Aldrete, M., Trujillo-Ferrara, J. G., Correa-Basurto, J. and Mexica-Ochoa, C., 2012. Effect of the lipophilic parameter (log P) on the anti-parasitic activity of imidazo [1, 2-a] pyridine derivatives. Medicinal Chemistry Research, 21 (4), pp. 415-420.
13. Koubachi, J., El Kazzouli, S., Bousmina, M. and Guillaumet, G., 2014. Functionalization of imidazo [1, 2-a] pyridines by means of metal-catalyzed cross-coupling reactions. European Journal of Organic Chemistry, 2014 (24), pp. 5119-5138.
14. Lacerda, R. B., de Lima, C. K., da Silva, L. L., Romeiro, N. C., Miranda, A. L. P., Barreiro, E. J. and Fraga, C. A., 2009. Discovery of novel analgesic and anti-inflammatory 3-arylamine-imidazo [1, 2-a] pyridine symbiotic prototypes. Bioorganic & medicinal chemistry, 17 (1), pp. 74-84.
15. Deep, A., Kaur Bhatia, R., Kaur, R., Kumar, S., Kumar Jain, U., Singh, H., Batra, S., Kaushik, D. and Kishore Deb, P., 2017. Imidazo [1, 2-a] pyridine scaffold as prospective therapeutic agents. Current topics in medicinal chemistry, 17 (2), pp. 238-250.
16. Dam, J., Ismail, Z., Kurebwa, T., Gangat, N., Harmse, L., Marques, H. M., Lemmerer, A., Bode, M. L. and de Koning, C. B., 2017. Synthesis of copper and zinc 2-(pyridin-2-yl) imidazo [1, 2-a] pyridine complexes and their potential anticancer activity. European journal of medicinal chemistry, 126, pp. 353-368.
17. Scribner, A., Dennis, R., Lee, S., Ouvry, G., Perrey, D., Fisher, M., Wyvratt, M., Leavitt, P., Liberator, P., Gurnett, A. and Brown, C., 2008. Synthesis and biological activity of imidazopyridine anticoccidial agents: part II. European journal of medicinal chemistry, 43 (6), pp. 1123-1151. Bhale, P. S. 2013, 2, 1-6, 2013.
18. Bhale, P. S., Dongare, S. B. and Chanshetti, U. B., 2013. Synthesis and antimicrobial screening of chalcones containing imidazo [1, 2-a] pyridine nucleus. Research Journal of Chemical Sciences, 2231, p. 606X. Paengphua, P., & Chancharunee, S. 2018, 149 (10), 1835-1840.
19. Warshakoon, N. C., Wu, S., Boyer, A., Kawamoto, R., Sheville, J., Renock, S., Xu, K., Pokross, M., Evdokimov, A. G., Walter, R. and Mekel, M., 2006. A novel series of imidazo [1, 2-a] pyridine derivatives as HIF-1α prolyl hydroxylase inhibitors. Bioorganic & medicinal chemistry letters, 16 (21), pp. 5598-5601.
20. Starrett Jr, J. E., Montzka, T. A., Crosswell, A. R. and Cavanagh, R. L., 1989. Synthesis and biological activity of 3-substituted imidazo [1, 2-a] pyridines as antiulcer agents. Journal of medicinal chemistry, 32 (9), pp. 2204-2210.
21. Santra, S., Bagdi, A. K., Majee, A. and Hajra, A., 2013. Iron (III)-Catalyzed Cascade Reaction between Nitroolefins and 2-Aminopyridines: Synthesis of Imidazo [1, 2-a] Pyridines and Easy Access towards Zolimidine. Advanced Synthesis & Catalysis, 355 (6), pp. 1065-1070.
22. Said, M. S., Mishra, A., Pandole, S., Nayak, R. A., Kumar, P. and Gajbhiye, J. M., 2019. Regioselective One-Pot Synthesis of 3-Fluoro-Imidazo [1, 2-a] pyridines from Styrene. Asian Journal of Organic Chemistry, 8 (11), pp. 2143-2148.
23. Chitti, S., Singireddi, S., Reddy, P. S. K., Trivedi, P., Bobde, Y., Kumar, C., Rangan, K., Ghosh, B. and Sekhar, K. V. G. C., 2019. Design, synthesis and biological evaluation of 2-(3, 4-dimethoxyphenyl)-6 (1, 2, 3, 6-tetrahydropyridin-4-yl) imidazo [1, 2-a] pyridine analogues as antiproliferative agents. Bioorganic & Medicinal Chemistry Letters, 29 (18), pp. 2551-2558.
24. Ducray, R., Boutron, P., Didelot, M., Germain, H., Lach, F., Lamorlette, M., Legriffon, A., Maudet, M., Ménard, M., Pasquet, G. and Renaud, F., 2010. A versatile route to 3-(pyrimidin-4-yl)-imidazo [1, 2-a] pyridines and 3-(pyrimidin-4-yl)-pyrazolo [1, 5-a] pyridines. Tetrahedron letters, 51 (36), pp. 4755-4758.
25. Kurva, M., Pharande, S. G., Quezada-Soto, A. and Gámez-Montaño, R., 2018. Ultrasound assisted green synthesis of bound type bis-heterocyclic carbazolyl imidazo [1, 2-a] pyridines via Groebke-Blackburn-Bienayme reaction. Tetrahedron Letters, 59 (16), pp. 1596-1599.
26. Balalaie, S., Derakhshan-Panah, F., Zolfigol, M. A. and Rominger, F., 2018. A Convenient Method for the Synthesis of Imidazo [1, 2-a] pyridines with a New Approach. Synlett, 29 (01), pp. 89-93.
27. Tiwari, G., Kumar, M., Chauhan, A. N. S. and Erande, R. D., 2022. Recent advances in cascade reactions and their mechanistic insights: a concise strategy to synthesize complex natural products and organic scaffolds. Organic & Biomolecular Chemistry.
28. Neto, J. S., Balaguez, R. A., Franco, M. S., de Sa Machado, V. C., Saba, S., Rafique, J., Galetto, F. Z. and Braga, A. L., 2020. Trihaloisocyanuric acids in ethanol: an eco-friendly system for the regioselective halogenation of imidazo-heteroarenes. Green Chemistry, 22 (11), pp. 3410-3415.
29. Xia, B., Yan, D., Bai, Y., Xie, J., Cao, Y., Liao, D. and Lin, L., 2015. Determination of phenolic acids in Prunella vulgaris L.: a safe and green extraction method using alcohol-based deep eutectic solvents. Analytical Methods, 7 (21), pp. 9354-9364.
30. Pericherla, K., Kaswan, P., Pandey, K. and Kumar, A., 2015. Recent developments in the synthesis of imidazo [1, 2-a] pyridines. Synthesis, 47 (07), pp. 887-912.
31. Kurteva, V. B., Lubenov, L. A. and Antonova, D. V., 2014. On the mechanism of the direct acid catalyzed formation of 2, 3-disubstituted imidazo [1, 2-a] pyridines from 2-aminopyridines and acetophenones. Concurrence between ketimine and Ortoleva–King type reaction intermediated transformations. RSC advances, 4 (1), pp. 175-184.
32. Krasovsky, A. L., Nenajdenko, V. G. and Balenkova, E. S., 2002. A facile access to 2-CF3-imidazo [1, 2-a] pyridines. Synthesis, 2002 (10), pp. 1379-1384.
33. Yadav, J. S., Reddy, B. S., Rao, Y. G., Srinivas, M. and Narsaiah, A. V., 2007. Cu (OTf) 2-catalyzed synthesis of imidazo [1, 2-a] pyridines from α-diazoketones and 2-aminopyridines. Tetrahedron Letters, 48 (43), pp. 7717-7720.
34. Shaikh, M., Shaikh, M., Wagare, D., Ahmed Sheikh, A. and Sultan Kasim, S., 2022. Deep Eutectic Solvent (DES) Mediated Multicomponent Synthesis of 4-thiazolidinone-5-carboxylic Acid: A Green Chemistry Approach. Current Catalysis, 11 (1), pp. 65-70.
35. Wagare, D. S., Shaikh, M. H., Farooqui, M. and Durrani, A. N., Ultrasound promoted one-pot synthesis of imidazo [1, 2-a] pyridines in water.
36. Shaikh, M., Wagare, D., Farooqui, M. and Durrani, A., 2020. Microwave assisted synthesis of novel schiff bases of pyrazolyl carbaldehyde and triazole in PEG-400. Polycyclic Aromatic Compounds, 40 (5), pp. 1315-1320.
37. Harris, A. R., Nason, D. M., Collantes, E. M., Xu, W., Chi, Y., Wang, Z., Zhang, B., Zhang, Q., Gray, D. L. and Davoren, J. E., 2011. Synthesis of 5-bromo-6-methyl imidazopyrazine, 5-bromo and 5-chloro-6-methyl imidazopyridine using electron density surface maps to guide synthetic strategy. Tetrahedron, 67 (47), pp. 9063-9066.
38. Kondo, T., Kotachi, S., Ogino, S. I. and Watanabe, Y., 1993. Ruthenium Complex-catalyzed Novel and Facile Synthesis of Imidazo [1, 2-a] pyridines from 2-Aminopyridines and vicinal-Diols. Chemistry letters, 22 (8), pp. 1317-1320.
39. Zhu, D. J., Chen, J. X., Liu, M. C., Ding, J. C. and Wu, H. Y., 2009. Catalyst: and solvent-free synthesis of imidazo [1, 2-a] pyridines. Journal of the Brazilian Chemical Society, 20, pp. 482-487.
40. Gudmundsson, K. S. and Johns, B. A., 2003. Synthesis of novel imidazo [1, 2-a] pyridines with potent activity against herpesviruses. Organic Letters, 5 (8), pp. 1369-1372.
41. Vekariya, R. H., Patel, K. D. and Patel, H. D., 2016. Fruit juice of Citrus limon as a biodegradable and reusable catalyst for facile, eco-friendly and green synthesis of 3, 4-disubstituted isoxazol-5 (4H)-ones and dihydropyrano [2, 3-c]-pyrazole derivatives. Research on Chemical Intermediates, 42 (10), pp. 7559-7579.
42. Roslan, I. I., Ng, K. H., Wu, J. E., Chuah, G. K. and Jaenicke, S., 2016. Synthesis of Disubstituted 3-Phenylimidazo [1, 2-a] pyridines via a 2-Aminopyridine/CBrCl3 α-Bromination Shuttle. The Journal of organic chemistry, 81 (19), pp. 9167-9174.