Advertisement

Journal of Flow Chemistry

, Volume 6, Issue 4, pp 297–301 | Cite as

Application of Flow Chemistry to Macrocyclization of Crown Ethers

  • Tamás Fődi
  • József Kupai
  • György Túrós
  • Tamás Németh
  • Eszter Rojik
  • Eszter Riethmüller
  • György Tibor Balogh
  • Péter Huszthy
Article

Abstract

This paper reports a new continuous-flow synthesis of chiral and achiral pyridino-18-crown-6 ethers. Macrocyclizations have been performed in a packed-bed flow reactor where deprotonation of a bifunctional primary or a secondary alcohol takes place with potassium hydroxide as a heterogeneous base avoiding the use of stronger and more dangerous one, sodium hydride. Ditosylate derivatives of pyridine as precursors for the macrocyclization used in batch condition were replaced by the appropriate diiodides and optimization of the parameters provided higher yields in shorter reaction times. The setup presented here is suitable for the preparation of different ethers by Williamsontype syntheses in continuous-flow reactions.

Keywords

flow chemistry crown ether Williamson-type ether syntheses macrocyclization 

Supplementary material

41981_2016_6040297_MOESM1_ESM.pdf (142 kb)
Supplementary material, approximately 145 KB.

References

  1. 1.
    Pirkle, W. H.; Pochapsky, T. C. Chem. Rev. 1989, 89, 347–362.CrossRefGoogle Scholar
  2. 2.
    Bradshaw, J. S.; Huszthy, P.; Wang, T.; Zhu, C.; Nazarenko, A. Y.; Izatt, R. M. Supramol. Chem. 1993, 1, 267–275.CrossRefGoogle Scholar
  3. 3.
    Huszthy, P.; Bradshaw, J. S.; Bodurov, A. V.; Izatt, R. M. ACH-Models Chem. 1994, 131, 445–454.Google Scholar
  4. 4.
    Köntös, Z.; Huszthy, P.; Bradshaw, J. S.; Izatt, R. M. Tetrahedron Asymmetry 1999, 10, 2087–2099.CrossRefGoogle Scholar
  5. 5.
    Kontos, Z.; Huszthy, P.; Bradshaw, J. S.; Izatt, R. M. Enantiomer 2000, 5, 561–566.Google Scholar
  6. 6.
    Horvath, G.; Huszthy, P.; Szarvas, S.; Szókan, G.; Redd, J. T.; Bradshaw, J. S.; Izatt, R. M. Ind. Eng. Chem. Res. 2000, 39, 3576–3581.CrossRefGoogle Scholar
  7. 7.
    Farkas, V.; Tóth, T.; Orosz, G.; Huszthy, P.; Hollósi, M. Tetrahedron: Asymmetry 2006, 17, 1883–1889.CrossRefGoogle Scholar
  8. 8.
    Kupai, J.; Lévai, S.; Antal, K.; Balogh, G. T.; Tóth, T.; Huszthy, P. Tetrahedron Asymmetry 2012, 23, 415–427.CrossRefGoogle Scholar
  9. 9.
    Zhang, X. X.; Bradshaw, J. S.; Izatt, R. M. Chem. Rev. 1997, 97, 3313–3362.CrossRefGoogle Scholar
  10. 10.
    Bradshaw, J. S.; Thompson, P. K.; Izatt, R. M.; Morin, F. G.; Grant, D. M. J. Heterocycl. Chem. 1984, 21, 897–901.CrossRefGoogle Scholar
  11. 11.
    Bradshaw, J. S.; Huszthy, P.; McDaniel, C. W.; Zhu, C. Y.; Dalley, N. K.; Izatt, R. M.; Lifson, S. J. Org. Chem. 1990, 55, 3129–3137.CrossRefGoogle Scholar
  12. 12.
    Huszthy, P.; Bradshaw, J. S.; Zhu, C. Y.; Izatt, R. M. J. Org. Chem. 1991, 56, 3330–3336.CrossRefGoogle Scholar
  13. 13.
    Huszthy, P.; Oue, M.; Bashaw, J. S.; Zhu, C. Y.; Wang, T.; Dalley, N. K.; Curtis, J. C.; Izatt, R.M. J. Org. Chem. 1992, 57, 5383–5394.CrossRefGoogle Scholar
  14. 14.
    Habata, Y.; Bradshaw, J. S.; Young, J. J.; Castle, S. L.; Huszthy, P.; Pyo, T.; Lee, M. L.; Izatt, R. M. J. Org. Chem. 1996, 61, 8391–8396.CrossRefGoogle Scholar
  15. 15.
    Cooper, S. R. Crown Compounds: Toward Future Applications; Wiley- VCH: New York, 1992.Google Scholar
  16. 16.
    Samu, E.; Huszthy, P.; Horvath, G.; Szöllösy, A.; Neszmélyi, A. Tetrahedron Asymmetry 1999, 10, 3615–3626.CrossRefGoogle Scholar
  17. 17.
    Izatt, R. M.; Wang, T.; Hathaway, J. K.; Zhang, X. X.; Curtis, J. C.; Bradshaw, J. S.; Zhu, C. Y.; Huszthy, P. J. Incl. Phenom. Mol. Recognit. Chem. 1994, 17, 157–175.CrossRefGoogle Scholar
  18. 18.
    Bailey, P. D.; Everitt, S. R. L.; Morgan, M.; Brewster, A. G. Science 2001, 57, 1379–1386.Google Scholar
  19. 19.
    Lévai, S.; Németh, T.; Fodi, T.; Kupai, J.; Tóth, T.; Huszthy, P.; Balogh, G. T. J. Pharm. Biomed. Anal. 2015, 115, 192–195.CrossRefGoogle Scholar
  20. 20.
    Uiterwijk, J. W. H. M.; Van Staveren, C. J.; Reinhoudt, D. N.; Den Hertog Jr., H. J.; Kruise, L.; Harkema, S. J. Org. Chem. 1986, 51, 1575–1587.CrossRefGoogle Scholar
  21. 21.
    Huszthy, P.; Kertesz, J.; Bradshaw, J. S.; Izatt, R. M.; Redd, J. T. J. Heterocycl. Chem. 2001, 38, 1259–1264.CrossRefGoogle Scholar
  22. 22.
    Horvath, G.; Huszthy, P. Tetrahedron: Asymmetry 1999, 10, 4573–4583.CrossRefGoogle Scholar
  23. 23.
    Szemenyei, B.; Móczar, I.; Pal, D.; Kocsis, I.; Baranyai, P.; Huszthy, P. Chirality 2016, 28, 562–568.CrossRefGoogle Scholar
  24. 24.
    Tahri, A.; Cielen, E.; Van Aken, K. J.; Hoornaert, G. J.; De Schryver, F. C.; Boens, N. J. Chem. Soc. Perkin Trans. 2 1999, 2, 1739–1748.CrossRefGoogle Scholar
  25. 25.
    Kupai, J.; Huszthy, P.; Katz, M.; Tóth, T. Arkivoc 2012, 134–145.Google Scholar
  26. 26.
    Jas, G.; Kirschning, A. Chem. Eur. J. 2003, 9, 5708–5723.CrossRefGoogle Scholar
  27. 27.
    Watts, P.; Haswell, S. J. Chem. Soc. Rev. 2005, 34, 235–246.CrossRefGoogle Scholar
  28. 28.
    Microchemical Engineering in Practice; Dietrich, T. R., Ed.; John Wiley & Sons, Inc.: Hoboken, NJ, USA, 2009.Google Scholar
  29. 29.
    Wiles, C.; Watts, P. Green Chem. 2012, 14, 38–54.CrossRefGoogle Scholar
  30. 30.
    Newman, S. G.; Jensen, K. F. Green Chem. 2013, 15, 1456–1472.CrossRefGoogle Scholar
  31. 31.
    Irfan, M.; Glasnov, T. N.; Kappe, C. O. ChemSusChem 2011, 4, 300–316.CrossRefGoogle Scholar
  32. 32.
    Munirathinam, R.; Huskens, J.; Verboom, W. Adv. Synth. Catal. 2015, 357, 1093–1123.CrossRefGoogle Scholar
  33. 33.
    McQuade, D. T.; Seeberger, P. H. J. Org. Chem. 2013, 78, 6384–6389.CrossRefGoogle Scholar
  34. 34.
    Riva, E.; Rencurosi, A.; Gagliardi, S.; Passarella, D.; Martinelli, M. Chem. Eur. J. 2011, 17, 6221–6226.CrossRefGoogle Scholar
  35. 35.
    Baker, A.; Graz, M.; Saunders, R.; Evans, G. J. S.; Pitotti, I.; Wirth, T. J. Flow Chem. 2015, 5, 65–68.CrossRefGoogle Scholar
  36. 36.
    Maes, V.; Pirotte, G.; Brebels, J.; Verstappen, P.; Lutsen, L.; Vanderzande, D.; Maes, W. J. Flow Chem. 2015, 5, 201–209.CrossRefGoogle Scholar
  37. 37.
    Longab, B.; Zhaoa, D.; Liu, W. Ind. Eng. Chem. Res. 2012, 51, 9456–9467.CrossRefGoogle Scholar
  38. 38.
    Suh, H.; Kim, J.-K.; Jung, I.-S.; Lee, S.-E.; Kang, S. W.; Park, J.-S. Bull. Korean Chem. Soc. 1998, 19, 411–414.Google Scholar
  39. 39.
    Perry, R. H.; Green, D. W. Perry’s Chemical Engineers’ Handbook, 15th ed.; McGraw-Hill: New York, 2008.Google Scholar
  40. 40.
    Cooper, K. D.; Walborsky, H. M. J. Org. Chem. 1981, 3, 2110–2116.CrossRefGoogle Scholar
  41. 41.
    Horvath, G.; Rusa, C.; Köntös, Z. Synth. Commun. 1999, 27, 3719–3731.Google Scholar
  42. 42.
    Grootenhuis, P. D. J.; Uiterwijk, J. W. H. M.; Reinhoudt, D. N.; van Staveren, C. J.; Sudhölter, E. J. R.; Bos, M.; van Eerden, J.; Klooster, W. T.; Kruise, L.; Harkema, S. J. Am. Chem. Soc. 1986, 108, 780–788.CrossRefGoogle Scholar

Copyright information

© Akadémiai Kiadó 2016

Authors and Affiliations

  • Tamás Fődi
    • 1
  • József Kupai
    • 1
  • György Túrós
    • 2
  • Tamás Németh
    • 1
  • Eszter Rojik
    • 1
  • Eszter Riethmüller
    • 2
  • György Tibor Balogh
    • 1
    • 2
  • Péter Huszthy
    • 1
  1. 1.Department of Organic Chemistry and TechnologyBudapest University of Technology and EconomicsBudapestHungary
  2. 2.Compound Profiling LaboratoryChemical Works of Gedeon Richter Plc.BudapestHungary

Personalised recommendations