ORGANIC
LETTERS
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Vol. XX, No. XX
000–000
Sc(OTf)3‑Catalyzed Dehydrogenative
Cyclization for Synthesis of
N‑Methylacridones
Xi-An Li,† Hong-Li Wang,† and Shang-Dong Yang*,†,‡
State Key Laboratory of Applied Organic Chemistry, Lanzhou University,
Lanzhou 730000, P. R. China, and State Key Laboratory for Oxo Synthesis and Selective
Oxidation, Lanzhou Institute of Chemical Physics, Lanzhou 730000, P. R. China
Received December 17, 2012
ABSTRACT
A novel method has been developed for the synthesis of substituted N-methylacridones from 2-(N-methyl-N-phenylamino)benzaldehydes via
dehydrogenative cyclization. This transformation involves two primary processes: the aldehyde first coordinates with Sc(OTf)3 and induces the
aromaticelectrophilic substitution (SEAr) reaction toform the active intermediate N-methyl-acridin-9-ol, which is thenquickly oxidized in situ toafford
the acridones. Furthermore, the procedure involved is both environmental friendly and atom efficient; H2O is the only byproduct in this reaction.
Acridone and its derivatives are versatile heteroaromatic
compounds that exhibit a variety of biological activities
and pharmacological properties. Uses include anti-HIV
and antiviral activity, against bovine viral diarrhea virus
(BVDV), as well as antihelminthic, antimalarial, anti-
cancer, antitumor, and antifungal activities.1 Common
methods for the synthesis of acridones are the acid-induced
ring closure of N-phenyl anthranilic acids, which can be
obtained from Ullmann condensation of anilines with
ortho-halogen-substituted benzoic acids.2 Recently, the
Larock group has reported a new approach based on an
annulation reaction utilizing salicylates and silylaryl tri-
flates plus CsF.3 A similar method was reported in 2009 by
Greaney’s group, who accessed acridones from readily
available o-halobenzamides through initial aryne R-insertion,
followed by in situ SNAr reactions.4 Moreover, Snieckus
disclosed a new method for the synthesis of acridones
through an application of a combined BuchwaldꢀHartwig
† Lanzhou University.
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Ferguson, D. M. Bioorg. Med. Chem. 2006, 14, 5467. (c) Pal, C.; Kundu,
M. K.; Bandyopadhyay, U.; Adhikari, S. Bioorg. Med. Chem. Lett. 2011,
21, 3563. (d) Allen, C. F. H.; Mckee, G. H. W. Org. Syn. 1943, 2, 15.
(3) (a) Zhao, J.; Larock, R. C. J. Org. Chem. 2007, 72, 583. (b) Liu, Z.;
Larock, R. C. J. Am. Chem. Soc. 2005, 127, 13112. (c) Dubrovskiy, A. V.;
Larock, R. C. Org. Lett. 2011, 13, 4136.
(4) (a) Pintori, D. G.; Greaney, M. F. Org. Lett. 2010, 12, 168. (b)
Cant, A. A.; Bertrand, G. H. V.; Henderson, J. L.; Roberts, L.; Greaney,
M. F. Angew. Chem., Int. Ed. 2009, 48, 5199. (c) Henderson, J. L.;
Edwards, A. S.; Greaney, M. F. Org. Lett. 2007, 9, 5589. (d) Henderson,
J. L.; Edwards, A. S.; Greaney, M. F. J. Am. Chem. Soc. 2006, 128, 7426.
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‡ Lanzhou Institute of Chemical Physics.
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r
10.1021/ol400371h
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