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A one-pot synthesis of piperidinium spirooxindoline-pyridineolates and indole-substituted pyridones in aqueous or ethanol medium

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Abstract

Piperidinium spirooxindoline-pyridineolate has been prepared via one-pot multicomponent reaction of isatin, malononitrile, cyanoacetohydrazide, and piperidine in water or ethanol medium at room temperature. In addition, the synthesis of two indole-substituted 2-pyridones from indole-3-carbaldehyde, malononitrile, and cyanoacetohydrazide in the presence of piperidine is described.

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Fig. 1
Scheme 1
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Abbreviations

TLC:

Thin-layer chromatography

RT:

Room temperature

MeCN:

Acetonitrile

NR:

No reaction

FT-IR:

Fourier-transform infrared

MCR:

Multicomponent reaction

References

  1. Tauro SJ, Gawad JB (2013) Green chemistry: A boon to pharmaceutical synthesis. Int J Sci Res 2:67–69. https://doi.org/10.15373/22778179/JULY2013/22

    Article  Google Scholar 

  2. Simon MO, Li CJ (2012) Green chemistry oriented organic synthesis in water. Chem Soc Rev 41:1415–1427. https://doi.org/10.1039/C1CS15222J

  3. Bigi F, Carloni S, Ferrari L, Maggi R, Mazzacani A, Sartori G (2001) Clean synthesis in water. Part 2: Uncatalysed condensation reaction of Meldrum’s acid and aldehydes. Tetrahedron Lett 42:5203–5205. https://doi.org/10.1016/S0040-4039(01)00978-9

    Article  CAS  Google Scholar 

  4. Clark JH, Macquarrie DJ (2008) (Eds.). Handbook of Green Chemistry and Technology. John Wiley & Sons. https://doi.org/10.1002/9780470988305

  5. Li Y, Chen H, Shi C, Shi D, Ji S (2010) Efficient one-pot synthesis of spirooxindole derivatives catalyzed by l-proline in aqueous medium. J Comb Chem 12:231–237. https://doi.org/10.1021/cc9001185

    Article  CAS  PubMed  Google Scholar 

  6. Yan LJ, Wang YC (2016) Recent advances in green synthesis of 3, 3′-spirooxindoles via isatin–based one–pot multicomponent cascade reactions in aqueous medium. ChemistrySelect 1:6948–6960. https://doi.org/10.1002/slct.201601534

    Article  CAS  Google Scholar 

  7. Yu B, Yu DQ, Liu HM (2015) Spirooxindoles: Promising scaffolds for anticancer agents. Eur J Med Chem 97:673–698. https://doi.org/10.1016/j.ejmech.2014.06.056

    Article  CAS  PubMed  Google Scholar 

  8. Yu B, Yu Z, Qi PP, Yu DQ, Liu HM (2015) Discovery of orally active anticancer candidate CFI-400945 derived from biologically promising spirooxindoles: Success and challenges. Eur J Med Chem 95:35–40. https://doi.org/10.1016/j.ejmech.2015.03.020

    Article  CAS  PubMed  Google Scholar 

  9. Ye N, Chen H, Wold EA, Shi PY, Zhou J (2016) Therapeutic potential of spirooxindoles as antiviral agents. ACS Infect Dis 2:382–392. https://doi.org/10.1021/acsinfecdis.6b00041

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Zhou LM, Qu RY, Yang GF (2020) An overview of spirooxindole as a promising scaffold for novel drug discovery. Expert Opin Drug Discovery 15:603–625. https://doi.org/10.1080/17460441.2020.1733526

    Article  CAS  Google Scholar 

  11. Panda SS, Jones RA, Bachawala P, Mohapatra PP (2017) Spirooxindoles as potential pharmacophores. Mini-Rev Med Chem 17:1515–1536. https://doi.org/10.2174/1389557516666160624125108

    Article  CAS  PubMed  Google Scholar 

  12. Pavlovska TL, Redkin RG, Lipson VV, Atamanuk DV (2016) Molecular diversity of spirooxindoles. Synth Biol Activity Mol Divers 20:299–344. https://doi.org/10.1007/s11030-015-9629-8

    Article  CAS  Google Scholar 

  13. Hien TT, White NJ, Thuy-Nhien NT, Hoa NT, Thuan PD, Tarning J, Hamed K (2017) Estimation of the in vivo MIC of cipargamin in uncomplicated Plasmodium falciparum malaria. Antimicrob Agents Chemother. https://doi.org/10.1128/AAC.01940-16

    Article  PubMed  PubMed Central  Google Scholar 

  14. Rojas-Duran R, González-Aspajo G, Ruiz-Martel C, Bourdy G, Doroteo-Ortega VH, Alban-Castillo J, Deharo E (2012) Anti-inflammatory activity of Mitraphylline isolated from uncaria tomentosa bark. J Ethnopharmacol 143:801–804. https://doi.org/10.1016/j.jep.2012.07.015

    Article  CAS  PubMed  Google Scholar 

  15. Sebahar PR, Osada H, Usui T, Williams RM (2002) Asymmetric, stereocontrolled total synthesis of (+) and (−)-spirotryprostatin B via a diastereoselective azomethine ylide [1, 3]-dipolar cycloaddition reaction. Tetrahedron 58:6311–6322. https://doi.org/10.1016/S0040-4020(02)00630-0

    Article  CAS  Google Scholar 

  16. Kang TH, Matsumoto K, Tohda M, Murakami Y, Takayama H, Kitajima M, Watanabe H (2002) Pteropodine and isopteropodine positively modulate the function of rat muscarinic M1 and 5-HT2 receptors expressed in Xenopus oocyte. Eur J Pharmacol 444:39–45. https://doi.org/10.1016/s0014-2999(02)01608-4

    Article  CAS  PubMed  Google Scholar 

  17. Mei GJ, Shi F (2018) Catalytic asymmetric synthesis of spirooxindoles: recent developments. Chem Commun 54:6607–6621. https://doi.org/10.1039/C8CC02364F

    Article  CAS  Google Scholar 

  18. Youseftabar-Miri L, Hosseinjani-Pirdehi H, Akrami A, Hallajian S (2020) Recent investigations in the synthesis of spirooxindole derivatives by Iranian researchers. J Iran Chem Soc 17:2179–2231. https://doi.org/10.1007/s13738-020-01921-2

    Article  CAS  Google Scholar 

  19. Xia M, Ma RZ (2014) Recent progress on routes to spirooxindole systems derived from isatin. J Heterocycl Chem 51:539–554. https://doi.org/10.1002/jhet.1114

    Article  CAS  Google Scholar 

  20. Ball-Jones NR, Badillo JJ, Franz AK (2012) Strategies for the enantioselective synthesis of spirooxindoles. Org Biomol Chem 10:5165–5181. https://doi.org/10.1039/C2OB25184A

    Article  CAS  PubMed  Google Scholar 

  21. Bariwal J, Voskressensky LG, Van der Eycken EV (2018) Recent advances in spirocyclization of indole derivatives. Chem Soc Rev 47:3831–3848. https://doi.org/10.1039/C7CS00508C

    Article  PubMed  Google Scholar 

  22. Nasri S, Bayat M, Mirzaei F (2021) Recent strategies in the synthesis of spiroindole and spirooxindole scaffolds. Top Curr Chem 379:1–37. https://doi.org/10.1007/s41061-021-00337-7

    Article  CAS  Google Scholar 

  23. Stahl PH, Wermuth CG (2003) Handbook of pharmaceutical salts: properties, selection and use. J Med Chem 46:1277. https://doi.org/10.1021/jm030019n

    Article  CAS  Google Scholar 

  24. Berry DJ, Steed JW (2017) Pharmaceutical cocrystals, salts and multicomponent systems; intermolecular interactions and property based design. Drug Delivery Rev 117:3–24. https://doi.org/10.1016/j.addr.2017.03.003

    Article  CAS  Google Scholar 

  25. Głowacki ED, Irimia-Vladu M, Bauer S, Sariciftci NS (2013) Hydrogen-bonds in molecular solids–from biological systems to organic electronics. J Mater Chem B 1:3742–3753. https://doi.org/10.1039/C3TB20193G

    Article  PubMed  Google Scholar 

  26. Fatahpour M, Hazeri N, Maghsoodlou MT, Sadeh FN, Lshkari M (2018) One-pot multicomponent synthesis of piperidinium 3,3’-(arylmethylene) bis (2-hydroxynaphthalene-1,4-diones): NMR spectroscopic and X-ray structure characterization. Turk J Chem 42:908–917. https://doi.org/10.3906/kim-1712-52

    Article  CAS  Google Scholar 

  27. Baharfar R, Asghari S, Zaheri F, Shariati N (2017) Three-component synthesis of novel spirooxindole–furan derivatives using pyridinium salts. C R Chim 20:359–364. https://doi.org/10.1016/j.crci.2016.07.001

    Article  CAS  Google Scholar 

  28. Sun J, Shen GL, Huang Y, Yan CG (2017) Formation of diverse polycyclic spirooxindoles via three-component reaction of isoquinolinium salts, isatins and malononitrile. Sci Rep 7:41024. https://doi.org/10.1038/srep41024

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Bashkar M, Bavadi M, Ghaderi E, Niknam K (2020) Synthesis of mono-and bis-spirooxindole derivatives on water using double salt of aluminum sulfate–sulfuric acid as a reusable catalyst. Mol Diversity. https://doi.org/10.1007/s11030-020-10091-5

    Article  Google Scholar 

  30. Bayat M, Nasri S, Notash B (2017) Synthesis of new 3-cyanoacetamide pyrrole and 3-acetonitrile pyrrole derivatives. Tetrahedron 73:1522–1527. https://doi.org/10.1016/j.tet.2017.02.005

    Article  CAS  Google Scholar 

  31. Bayat M, Nasri S (2017) A catalyst-free approach to regioselective synthesis of multi-functional 1H-pyrrolo[1,2-a]fused[1,3]diazaheterocycle using ketene dithioacetals in water–ethanol media. Tetrahedron Lett 58:3107–3111. https://doi.org/10.1016/j.tetlet.2017.06.076

    Article  CAS  Google Scholar 

  32. Mohammadi A, Bayat M, Nasri S (2019) Catalyst-free four-component domino synthetic approach toward versatile multicyclic spirooxindole pyran scaffolds. RSC Adv 9:16525–16533. https://doi.org/10.1039/C9RA03214B

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Hosseini H, Bayat M (2018) Cyanoacetohydrazides in synthesis of heterocyclic compounds. Top Curr Chem 376:1–67. https://doi.org/10.1007/s41061-018-0218-z

    Article  CAS  Google Scholar 

  34. Allam YA, Nawwar GA (2002) Facile synthesis of 3-spiroindolines. Heteroat Chem 13:207–210. https://doi.org/10.1002/hc.10020

    Article  CAS  Google Scholar 

  35. Hosseini H, Bayat M (2018) An efficient and ecofriendly synthesis of highly functionalized pyridones via a one-pot three-component reaction. RSC Adv 8:27131–27143. https://doi.org/10.1039/C8RA05690K

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Elmoghayar MRH, El-Agamey AGA, Nasr MYAS, Sallam MMM (1984) Activated nitriles in heterocyclic synthesis. Part III. Synthesis of N-amino-2-pyridone, pyranopyrazole and thiazolopyridine derivatives. J Heterocycl Chem 21:1885–1887. https://doi.org/10.1002/jhet.5570210660

    Article  CAS  Google Scholar 

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Acknowledgements

We thank the Iran National Science Foundation (Grant No. 98004758) for financial support. We acknowledge the support of this research from Imam Khomeini International University.

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Authors and Affiliations

  1. Department of Chemistry, Faculty of Science, Imam Khomeini International University, Qazvin, Iran

    Faezeh Mirzaei, Mohammad Bayat & Shima Nasri

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  1. Faezeh Mirzaei
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Correspondence to Mohammad Bayat.

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Mirzaei, F., Bayat, M. & Nasri, S. A one-pot synthesis of piperidinium spirooxindoline-pyridineolates and indole-substituted pyridones in aqueous or ethanol medium. Mol Divers 26, 2039–2048 (2022). https://doi.org/10.1007/s11030-021-10313-4

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