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Chemistry of Heterocyclic Compounds

, Volume 50, Issue 10, pp 1501–1505 | Cite as

Synthesis of 9-Phenylacridines via Ortho-Lithiation–Cyclization Sequence*

  • A. Kinens
  • T. Kalnins
  • E. SunaEmail author
Article

Acridine heterocycle is a core structure of the antimalarial drug Atabrine and antileukemia drug amsacrine. Acridines are widely used in development of anticancer medications [1, 2, 3, 4] and dyes [5, 6, 7]. There are also reports on the use of acridines as tools for DNA intercalation studies [8]. Not surprisingly, the development of new methods for the synthesis of acridines remains a focus of intense research [9, 10, 11, 12, 13].

Herein, we describe a previously unreported formation of acridines from triarylcarbinols under acidic conditions. Thus, treatment of tertiary alcohols 2a, b with conc. aqueous HCl in glacial AcOH at 90°C provided 9-phenylacridines 3a, b in 91-92% yield. The starting tertiary alcohols 2a, b were prepared by double addition of ortho-lithiated pivaloyl anilines 1a, b to benzoyl chloride in 76 and 68% yield, respectively. Overall, the two-step ortho-lithiation–cyclization sequence constitutes a convenient approach to 9-phenylacridines.

Keywords

acridine oxazine tertiary alcohol cyclization ortho-lithiation 

Notes

Authors thank Dr. S. Belyakov for X-ray crystallographic analysis.

Supplementary material

10593_2014_1616_MOESM1_ESM.pdf (776 kb)
ESM 1 (PDF 775 kb)

References

  1. 1.
    W. A. Denny, G. J. Atwell, P. B. Roberts, R. F. Anderson, M. Boyd, C. J. L. Lock, and W. R. Wilson, J. Med. Chem., 35, 4832 (1992).CrossRefGoogle Scholar
  2. 2.
    D. B. Capps, J. Dunbar, S. R. Kesten, J. Shillis, L. M. Werbel, J. Plowman, and D. L. Ward, J. Med. Chem., 35, 4770 (1992).CrossRefGoogle Scholar
  3. 3.
    B. F. Cain, R. N. Seelye, and G. J. Atwell, J. Med. Chem., 17, 922 (1974).CrossRefGoogle Scholar
  4. 4.
    S. T. Brennan, N. L. Colbry, R. L. Leeds, B. Leja, S. R. Priebe, M. D. Reily, H. D. H. Showalter, S. E. Uhlendorf, G. J. Atwell, and W. A. Denny, J. Heterocycl. Chem., 26, 1469 (1989).CrossRefGoogle Scholar
  5. 5.
    Z. Darzynkiewicz, Methods Cell. Biol., 33, 285 (1990).CrossRefGoogle Scholar
  6. 6.
    N. N. Vlasova, L. P. Golovkova, and N. G. Stukalina, Colloid J., 74, 22 (2012).CrossRefGoogle Scholar
  7. 7.
    R. Mosurkal, L. Hoke, S. A. Fossey, L. A. Samuelson, J. Kumar, D. Waller, and R. A. Gaudiana, J. Macromol. Sci., Part A: Pure Appl. Chem., 43, 1907 (2006).CrossRefGoogle Scholar
  8. 8.
    W. A. Denny, Curr. Med. Chem., 9, 1655 (2002).CrossRefGoogle Scholar
  9. 9.
    M. K. Kim and T. R. Kelly, J. Am. Chem. Soc., 116, 7072 (1994).CrossRefGoogle Scholar
  10. 10.
    B. W. Laursen and T. J. Sørensen, J. Org. Chem., 74, 3183 (2009).CrossRefGoogle Scholar
  11. 11.
    A. V. Dubrovskiy and R. C. Larock, J. Org. Chem., 77, 11232 (2012).CrossRefGoogle Scholar
  12. 12.
    A. Ueda, H. Wasa, S. Suzuki, K. Okada, K. Sato, T. Takui, and Y. Morita, Angew. Chem., Int. Ed., 51, 6691 (2012).CrossRefGoogle Scholar
  13. 13.
    R. Morioka, K. Hirano, T. Satoh, and M. Miura, Chem.-Eur. J., 20, 12720 (2014).CrossRefGoogle Scholar
  14. 14.
    N. Chinkov, A. Warm, and E. M. Carreira, Angew. Chem., Int. Ed., 50, 2957 (2011).CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2014

Authors and Affiliations

  1. 1.Latvian Institute of Organic SynthesisRigaLatvia

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