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Synlett 2019; 30(07): 817-820
DOI: 10.1055/s-0037-1612256
letter
© Georg Thieme Verlag Stuttgart · New York

Synthesis of Acridones by Palladium-Catalyzed Buchwald–Hartwig Amination

Julia Janke
a   Institute of Chemistry, University Rostock, Albert-Einstein-Str. 3a, 18059 Rostock, Germany   Email: peter.langer@uni-rostock.de
,
Alexander Villinger
a   Institute of Chemistry, University Rostock, Albert-Einstein-Str. 3a, 18059 Rostock, Germany   Email: peter.langer@uni-rostock.de
,
Peter Ehlers
a   Institute of Chemistry, University Rostock, Albert-Einstein-Str. 3a, 18059 Rostock, Germany   Email: peter.langer@uni-rostock.de
b   Leibniz-Institut für Katalyse e.V. an der Universität Rostock, A.-Einstein-Str. 29a, 18059 Rostock, Germany
,
Peter Langer*
a   Institute of Chemistry, University Rostock, Albert-Einstein-Str. 3a, 18059 Rostock, Germany   Email: peter.langer@uni-rostock.de
b   Leibniz-Institut für Katalyse e.V. an der Universität Rostock, A.-Einstein-Str. 29a, 18059 Rostock, Germany
› Author Affiliations
Further Information

Publication History

Received: 06 December 2018

Accepted after revision: 03 February 2019

Publication Date:
25 March 2019 (online)

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Abstract

The Buchwald–Hartwig amination allows an efficient and convenient synthesis of biologically and pharmaceutically important acridones by formation of a six-membered ring. With the described method, a number of derivatives have been synthesized in up to 95% yield by using a variety of anilines as well as benzylic and aliphatic amines.

Key words

palladium catalysis - Suzuki–Miyaura reaction - Buchwald–Hartwig amination - acridones - cyclization

Supporting Information

    Supporting information for this article is available online at https://doi.org/10.1055/s-0037-1612256.
  • Supporting Information
 

  • References and Notes

  • 1 Del Buttero P, Gironda R, Moret M, Papagni A, Parravicini M, Rizzato S, Miozzo L. Eur. J. Org. Chem. 2011; 2265
  • 2 Huang P.-C, Parthasarathy K, Cheng C.-H. Chem. Eur. J. 2013; 19: 460
    CrossrefPubMed
  • 3 Kobayashi K, Nakagawa K, Yuba S, Komatsu T. Helv. Chim. Acta 2013; 96: 389
    Crossref
  • 4 Pal C, Kundu MK, Bandyopadhyay U, Adhikari S. Bioorg. Med. Chem. Lett. 2011; 21: 3563
    CrossrefPubMed
  • 5 Zhao J, Larock RC. J. Org. Chem. 2007; 72: 583
    CrossrefPubMed
  • 6 Nishio R, Wessely S, Sugiura M, Kobayashi S. J. Comb. Chem. 2006; 8: 459
    CrossrefPubMed
    • 7a Mayur YC, Peters GJ, Lemos C, Kathmann I, Prasad VV. S. R. Arch. Pharm. 2009; 342: 640
      CrossrefPubMed
    • 7b Sathish NK, GopKumar P, Prasad VV. S. R, Kumar SM. S, Mayur YC. Med. Chem. Res. 2010; 19: 674
      Crossref
  • 8 Singh P, Kaur J, Yadav B, Komath SS. Bioorg. Med. Chem. 2009; 17: 3973
    CrossrefPubMed
    • 9a Hegde R, Thimmaiah P, Yerigeri MC, Krishnegowda G, Thimmaiah GN, Houghton PJ. Eur. J. Med. Chem. 2004; 39: 161
      CrossrefPubMed
    • 9b Allen CF. H. McKee G. H. W. 1939; 19: 6
    • 10a Suzuki N, Kazui Y, Kato M, Izawa Y. Heterocycles 1981; 16: 2121
      Crossref
    • 10b Suzuki N, Kazui Y, Tsukamoto T, Kato M, Izawa Y. Bull. Chem. Soc. Jpn. 1983; 1519
  • 11 Zhao J, Larock RC. J. Org. Chem. 2007; 72: 583
    CrossrefPubMed
    • 13a Hoang HD, Janke J, Amirjanyan A, Ghochikyan T, Flader A, Villinger A, Ehlers P, Lochbrunner S, Surkus A.-E, Langer P. Org. Biomol. Chem. 2018; 16: 6543
      CrossrefPubMed
    • 13b Pham NN, Janke S, Salman GA, Dang TT, Le TS, Spannenberg A, Ehlers P, Langer P. Eur. J. Org. Chem. 2017; 5554
    • 13c Ohlendorf L, Diaz Velandia JE, Konya K, Ehlers P, Villinger A, Langer P. Adv. Synth. Catal. 2017; 359: 1758
      Crossref
    • 13d Kitawaki T, Hayashi Y, Chida N. Heterocycles 2005; 65: 1561
      Crossref
    • 13e Nozaki K, Takahashi K, Nakano K, Hiyama T, Tang H.-Z, Fujiki M, Yamaguchi S, Tamao K. Angew. Chem. Int. Ed. 2003; 42: 2051
      CrossrefPubMed
    • 14a Christensen H, Schjoth-Eskesen C, Jensen M, Sinning S, Jensen HH. Chem. Eur. J. 2011; 17: 10618
      CrossrefPubMed
    • 14b Sato K, Inoue Y, Mori T, Sakaue A, Tarui A, Omote M, Kumadaki I, Ando A. Org. Lett. 2014; 16: 3756
      CrossrefPubMed
    • 15a Zhang L, Huang X, Zhen S, Zhao J, Li H, Yuan B, Yang G. Org. Biomol. Chem. 2017; 15: 6306
      CrossrefPubMed
    • 15b Zhang X, Yang Y, Liang Y. Tetrahedron Lett. 2012; 53: 6406
      Crossref
  • 16 Typical Procedure – Synthesis of 10-(4-Methylphenyl)-acridin-9(10H)-one (4a) A dried glass pressure tube under argon was charged with 2,2'-dibromobenzophenone 3a (100 mg, 0.3 mmol), Pd2dba3 (14 mg, 0.015 mmol), dppf (16 mg, 0.03 mmol), KOtBu (200 mg, 1.8 mmol), and amine (0.1 ml, 0.9 mmol). The solids were dissolved in dry toluene (3 mL), sealed with a Teflon® cap before being heated to 100 °C. After 24 h, the mixture was allowed to cool to room temperature. The residue was dissolved in CH2Cl2 (20 mL), washed with hydrochloric acid (1 M, 20 mL) and dried with Na2SO4. After filtration and removal of the solvents under reduced pressure, the crude solid was purified by column chromatography (heptane/ethyl acetate 10:1) to give 10-(4-methylphenyl)acridin-9(10H)-one (4a) as a yellow solid (80 mg, 95%), mp 290–292 °C. 1H NMR (300 MHz, CDCl3): δ = 8.58 (dd, 3 J = 8.0 Hz, 4 J = 2.1 Hz, 2 H, CHAr), 7.53–7.45 (m, 4 H, CHAr), 7.30–7.21 (m, 4 H, CHAr), 6.80 (d, 3 J = 9.0 Hz, 2 H, CHAr), 2.54 (s, 3 H, CH3). 13C NMR (75 MHz, CDCl3): δ = 178.2 (CO), 143.3 (2 CAr), 139.8 (CAr), 136.3 (CAr), 133.3 (2 CHAr), 131.8 (2 CHAr), 129.7 (2 CHAr), 127.3 (2 CHAr), 121.9 (2 CAr), 121.5 (2 CHAr), 117.0 (2 CHAr), 21.4 (CH3). IR (ATR, cm–1): 3033 (w), 2921 (w), 2853 (w), 1630 (m), 1596 (m), 1485 (m), 1456 (m), 1299 (m), 1271 (m), 1156 (m), 1038 (m), 1025 (m), 935 (m), 824 (m), 753 (s), 673 (m), 520 (m). MS (EI, 70 eV): m/z (%) = 286 (20), 285 ([M]+, 100), 284 (12), 241 (15), 166 (11), 140 (17), 139 (10), 91 (12), 89 (13), 77 (12), 76 (13), 65 (22), 63 (15), 50 (11), 39 (15). HRMS (EI): m/z [M]+ calcd for C20H15O1N1: 285.11482; found: 285.11482.
  • 17 Gao Q, Xu S. Org. Biomol. Chem. 2018; 16: 208
    CrossrefPubMed