ORGANIC
LETTERS
XXXX
Vol. XX, No. XX
Pd(II)-Catalyzed One-Pot, Three-Step
Route for the Synthesis of
Unsymmetrical Acridines
000–000
,
†
†
Hai-Ming Guo,* Run-Ze Mao, Qiao-Tian Wang, Hong-Ying Niu, Ming-Sheng Xie,
†
†,‡
†
,†
and Gui-Rong Qu*
School of Chemistry and Chemical Engineering, Henan Normal University,
Xinxiang 453007, Henan, China, and School of Chemistry and Chemical Engineering,
Henan Institute of Science and Technology, Xinxiang 453003, China
guohm518@hotmail.com; quguir@sina.com
Received September 9, 2013
ABSTRACT
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Unsymmetric acridines are synthesized via a one-pot amination/cyclization/aromatization reaction for the first time. With Pd(OAc) -X-Phos as the
catalyst, a series of unsymmetric acridines are obtained in moderate to excellent yields (up to 99% yield). Meanwhile, the diphenylamine
intermediate could be isolated, which is evidence of the domino process.
Acridines have attracted considerable attention due
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to their important biological and medicinal activities. As
sclerosing agent, is known to act as a histamine N-methyl-
4
transferase inhibitor. Since acridines have been proven
shown in Figure 1, Porflavine, a disinfectant bacteriostatic
against many gram-positive bacteria, has been approved
to be important in many areas, searching for a useful and
efficient approach for the synthesis of acridines is therefore
highly desirable.
The Bernthsen acridine synthesis, a name reaction, con-
sists of heating diphenylamine and carboxylic acids with
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zinc chloride as the catalyst (Scheme 1a). Later, Larock’s
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by the FDA as a drug. Acrisorcin, a new agent for the
control of tinea versicolor, has also been approved by the
3
FDA to serve as a drug. Mepacrine, an intrapleural
group developed a [4 þ 2] annulation of 2-aminoaryl ketones
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triflate with CsF (Scheme 1b). In 2010, Buchwald et al.
†
Henan Normal University.
Henan Institute of Science and Technology.
‡
with arynes generated in situ from o-(trimethylsilyl)aryl
(
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0.1021/ol402596g r XXXX American Chemical Society