GSCGreen and Sustainable Chemistry2160-6951Scientific Research Publishing10.4236/gsc.2021.113008GSC-111108ArticlesChemistry&Materials Science Bismuth (III) Chloride Catalyzed Multicomponent Synthesis of Substituted Hexahydroimidazo[1, 2-<i>a</i>]Pyridines NoahT. Haskin1RichardA. Guingrich1AllisonJ. Schrader1MatthewR. Crosse1AlpaY. Dave2EeshwaraiahBegari2RamS. Mohan1*Laboratory for Environmentally Friendly Organic Synthesis, Department of Chemistry, Illinois Wesleyan University, Bloomington, IL, USACentre for Applied Chemistry, School of Applied Material Sciences, Central University of Gujarat, Gandhinagar, India300720211103899514, July 20212, August 2021 5, August 2021© Copyright 2014 by authors and Scientific Research Publishing Inc. 2014This work is licensed under the Creative Commons Attribution International License (CC BY). http://creativecommons.org/licenses/by/4.0/

The synthesis of nitrogen containing heterocycles is of particular interest in the pharmaceutical industry due to the range of biological activities exhibited by such compounds. Their synthesis using multicomponent reactions saves steps and minimizes waste generation. The bismuth (III) chloride multicomponent synthesis of a series of hexahydroimidazo[1, 2- <i> a </i> ]pyridines is reported. Bismuth (III) compounds are especially attractive from a green chemistry perspective because they are remarkably nontoxic, non-corrosive and relatively inexpensive. The reported method avoids chromatography and an aqueous waste stream to afford the products in a very mass efficient manner.

Bismuth Chloride Green Chemistry Heterocycles Multicomponent ReactionsAcknowledgements

This material is based upon work supported by the National Science Foundation under CHE-1229133, which funded the purchase of a 400 MHz NMR spectrometer. RM would like to acknowledge an Artistic and Scholarly grant from Illinois Wesleyan University. We are also grateful to an anonymous reviewer for insightful comments.

Conflicts of Interest

The authors declare no conflicts of interest regarding the publication of this paper.

Cite this paper

Haskin, N.T., Guingrich, R.A., Schrader, A.J., Crosse, M.R., Dave, A.Y., Begari, E. and Mohan, R.S. (2021) Bismuth (III) Chloride Catalyzed Multicomponent Synthesis of Substituted Hexahydroimidazo[1, 2-a]Pyridines. Green and Sustainable Chemistry, 11, 89-95. https://doi.org/10.4236/gsc.2021.113008

ReferencesCabrele, C. and Reiser, O. (2016) The Modern Face of Synthetic Heterocyclic Chemistry. The Journal of Organic Chemistry, 81, 10109-10125. https://doi.org/10.1021/acs.joc.6b02034Taylor, A.P., Robinson, R.P., Fobian, Y.M., Blakemore, D.C., Jones, L.H. and Fadeyi, O. (2016) Modern Advances in Heterocyclic Chemistry in Drug Discovery. Organic & Biomolecular Chemistry, 14, 6611-6637. https://doi.org/10.1039/C6OB00936KKerru, N., Gummidi, L., Maddila, S., Gangu, K.K. and Jonnalagadda, S.B. (2020) A Review on Recent Advances in Nitrogen-Containing Molecules and Their Biological Applications. Molecules, 25, 1909. https://doi.org/10.3390/molecules25081909Hanson, S.M., Morlock, E.V., Satyshur, K.A. and Czajkowski, C. (2008) Structural Requirements for Eszopiclone and Zolpidem Binding to the GABAA Receptor Are Different. Journal of Medicinal Chemistry, 51, 7243-7252. https://doi.org/10.1021/jm800889mEnguehard-Gueiffier, C. and Gueiffier, A. (2007) Recent Progress in the Pharmacology of Imidazo[1,2-a]pyridines. Mini-Reviews in Medicinal Chemistry, 7, 888-899. https://doi.org/10.2174/138955707781662645Yan, R., Yan, H., Ma, C., et al. (2012) Cu(I)-Catalyzed Synthesis of Imidazo[1,2-a]pyridines from Aminopyridines and Nitroolefins Using Air as the Oxidant. Journal of Organic Chemistry, 77, 2024-2028. https://doi.org/10.1021/jo202447pStasyuk, A.J., Banasiewicz, M., Cyrański, M.K. and Gryko, D.T. (2012) Imidazo[1,2-a]pyridines Susceptible to Excited State Intramolecular Proton Transfer: One-Pot Synthesis via an Ortoleva-King Reaction. Journal of Organic Chemistry, 77, 5552-5558. https://doi.org/10.1021/jo300643wCai, Z., Wang, S. and Ji, S. (2013) Copper(I) Iodide/Boron Trifluoride Etherate-Cocatalyzed Aerobic Dehydrogenative Reactions Applied in the Synthesis of Substituted Heteroaromatic Imidazo[1,2-a]pyridines. Advanced Synthesis & Catalysis, 355, 2686-2692. https://doi.org/10.1002/adsc.201300333Monir, K., Bagdi, A.K., Ghosh, M. and Hajra, A. (2014) Unprecedented Catalytic Activity of Fe(NO3)3&middot;9H2O: Regioselective Synthesis of 2-Nitroimidazopyridines via Oxidative Amination. Organic Letters, 16, 4630-4633. https://doi.org/10.1021/ol502218uBagdi, A.K., Rahman, M., Santra, S., Majee, A. and Hajra, A. (2013) Copper-Catalyzed Synthesis of Imidazo[1,2-a]pyridines through Tandem Imine Formation-Oxidative Cyclization under Ambient Air: One-Step Synthesis of Zolimidine on a Gram-Scale. Advanced Synthesis & Catalysis, 355, 1741-1747. https://doi.org/10.1002/adsc.201300298Hiebel, M., Fall, Y., Scherrmann, M. and Berteina-Raboin, S. (2014) Straightforward Synthesis of Various 2,3-Diarylimidazo[1,2-a]pyridines in PEG400 Medium through One-Pot Condensation and C-H Arylation. European Journal of Organic Chemistry, 2014, 4643-4650. https://doi.org/10.1002/ejoc.201402079Pan, S., Wang, G., Schinazi, R.F. and Zhao, K. (1998) Synthesis of Novel Isoxazolinyl Substituted Imidazo[1,2-a]pyridine C-Nucleoside Analogs. Tetrahedron Letters, 39, 8191-8194. https://doi.org/10.1016/S0040-4039(98)01872-3Lhassani, M., Chavignon, O., Chezal, J., et al. (1999) Synthesis and Antiviral Activity of Imidazo[1,2-a]pyridines. European Journal of Medicinal Chemistry, 34, 271-274. https://doi.org/10.1016/S0223-5234(99)80061-0Gudmundsson, K.S., Drach, J.C. and Townsend, L.B. (1997) Synthesis of Imidazo[1,2-a]pyridine C-Nucleosides with an Unexpected Site of Ribosylation. The Journal of Organic Chemistry, 62, 3453-3459. https://doi.org/10.1021/jo9619342Márton-Merész, M., Zára-Kaczián, E., Boros, S. and Mátyus, P. (1997) Cyclocondensation Reaction of a 1,5-diketone with 1,2-diamines. Journal of Heterocyclic Chemistry, 34, 1033-1036. https://doi.org/10.1002/jhet.5570340350Shao, X., Zhang, W., Peng, Y., Li, Z., Tian, Z. and Qian, X. (2008) cis-Nitromethylene Neonicotinoids as New Nicotinic Family: Synthesis, Structural Diversity, and Insecticidal Evaluation of Hexahydroimidazo[1,2-alpha]pyridine. Bioorganic & Medicinal Chemistry Letters, 18, 6513-6516. https://doi.org/10.1016/j.bmcl.2008.10.048Türkmen, H., Ceyhan, N., ülkü Karabay Yavasoglu, N., Ozdemir, G. and Cetinkaya, B. (2011) Synthesis and Antimicrobial Activities of Hexahydroimidazo[1,5-a]pyridinium Bromides with Varying Benzyl Substituents. European Journal of Medicinal Chemistry, 46, 2895-2900. https://doi.org/10.1016/j.ejmech.2011.04.012Wang, R., Zhu, P., Lu, Y., Huang, F. and Hui, X. (2013) Bronsted Acid-Catalyzed Four-Component Cascade Reaction: Facile Synthesis of Hexahydroimidazo[1,2-a]pyridines. Advanced Synthesis & Catalysis, 355, 87-92. https://doi.org/10.1002/adsc.201200145Jiang, J., Zhang, M., Wu, W., Lu, H., Shi, Y. and Li, J. (2018) L-Phenylalanine Triflate as Organocatalyst for Divergent Approaches to Trisubstituted Hexahydroimidazo[1,2-a]pyridine and 1,4-Diazepane Derivatives. Synlett, 29, 246-250. https://doi.org/10.1055/s-0036-1589115Alvim, H.G.O., Correa, J.R., Assumpcao, J.A.F., da Silva, W.A., Rodrigues, M.O., de Macedo, J.L., Fioramonte, M., Gozzo, F.C., Gatto, C.C. and Neto, B.A.D. (2018) Heteropolyacid-Containing Ionic Liquid-Catalyzed Multicomponent Synthesis of Bridgehead Nitrogen Heterocycles: Mechanisms and Mitochondrial Staining. The Journal of Organic Chemistry, 83, 4044-4053. https://doi.org/10.1021/acs.joc.8b00472Tan, H. and Wang, Y. (2020) Facile Synthesis of Novel Hexahydroimidazo[1,2-a]pyridine Derivatives by One-Pot, Multicomponent Reaction under Ambient Conditions. ACS Combinatorial Science, 22, 468-474. https://doi.org/10.1021/acscombsci.0c00105https://pubchem.ncbi.nlm.nih.gov/compound/P-Toluenesulfonic-acid#section=Acute-EffectsMohan, R. (2010) Green Bismuth. Nature Chemistry, 2, 336. https://doi.org/10.1038/nchem.609Salvador, J.A.R., Silvestre, S.M., Pinto, R.M.A., Santos, R.C. and LeRoux, C. (2012) New Applications for Bismuth(III) Salts in Organic Synthesis: From Bulk Chemicals to Steroid and Terpene Chemistry. Topics in Current Chemistry, 311, 143-178. https://doi.org/10.1007/128_2011_170Bothwell, J.M., Krabbe, S.W. and Mohan, R.S. (2011) Applications of Bismuth(III) Compounds in Organic Synthesis. Chemical Society Reviews, 40, 4649-4707. https://doi.org/10.1039/c0cs00206bOllevier, T. (2013) New Trends in Bismuth-Catalyzed Synthetic Transformations. Organic & Biomolecular Chemistry, 11, 2740-2755. https://doi.org/10.1039/c3ob26537dhttps://pubchem.ncbi.nlm.nih.gov/compound/Bismuth-chloride-section=Acute-Effectshttps://pubchem.ncbi.nlm.nih.gov/compound/Sodium-chloride#section=Acute-EffectsSunderhaus, J.D. and Martin, S.E. (2009) Applications of Multicomponent Reactions to the Synthesis of Diverse Heterocyclic Scaffolds. Chemistry: A European Journal, 15, 1300-1308. https://doi.org/10.1002/chem.200802140