ORGANIC
LETTERS
XXXX
Vol. XX, No. XX
000–000
Iron-Catalyzed One-Pot
2,3-Diarylquinazolinone Formation
from 2‑Nitrobenzamides and Alcohols
Huamin Wang,† Xiangxiang Cao,† Fuhong Xiao,† Saiwen Liu,† and Guo-Jun Deng*,†,‡
Key Laboratory of Environmentally Friendly Chemistry and Application of Ministry of
Education, College of Chemistry, Xiangtan University, Xiangtan 411105, China, and
Key Laboratory of Molecular Recognition and Function, Institute of Chemistry, Chinese
Academy of Sciences, Beijing 100080, China
Received August 15, 2013
ABSTRACT
A novel approach for the synthesis of 2,3-diarylquinazolinones using iron as catalyst is described. Various 2-nitro-N-arylbenzamides reacted with
benzylic alcohols to selectively give the corresponding products in the absence of external oxidant or reductant.
Quinazolinone occurs widely in natural products such as
rutaecarpine from a Chinese herbal drug and luotonin A
from a Chinese plant (Peganum nigellastrum) (Figure 1).1
Substituted quinazolinones are assigned as privileged
structures in drug discovery. They play important roles
as key building blocks in the synthesis of a variety of drugs
such as anticonvulsant, antibacterial, anti-inflammatory,
and anticancer agents.2 As a result, there are numerous
efforts aimed at developing efficient and mild approaches
for the synthesis of substituted quinazolinones.3 Conven-
tional routes to substituted quinazolinones mainly rely on
coupling o-aminobenzamides with aldehyde,4 alcohol,5 as
well as other coupling reagents.6 2-Aminobenzoic acid and
its derivatives7 and 2-halogen-substiuted anilines8 are also
often used as starting materials for the preparation of
substituted quinazolinones. However, the presence of an
amino group sometimes resultes in product instability or
preparation difficulties. In recent years, replacing ortho-
functionalized anilines with other functionalized com-
pounds has attracted considerable interest. Among them,
o-bromobenzoic acid derivatives were the most used
(6) (a) Chen, G.; Kalchar, S.; Kuo, C.; Chang, C.; Usifoh, C.; Chern,
J. J. Org. Chem. 2003, 68, 2502. (b) Roopan, S.; Maiyalagan, T.; Khan,
F. Can. J. Chem. 2008, 1019. (c) Adib, M.; Ansari, S.; Mohammadi, A.;
Bijanzadeh, H. Tetrahedron Lett. 2010, 51, 30.
† Xiangtan University.
‡ Chinese Academy of Sciences.
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Mhaske, S. B.; Argade, N. P. Tetrahedron 2006, 62, 9787 and references
cited therein. (c) Ma, Z.; Hano, Y.; Nomura, T. Heterocycles 2005, 65,
2203.
(7) (a) Gschwend, H. W.; Rodriguez, H. R. Org. React. 1979, 26, 47.
€
(b) Sailer, M.; Franz, A. W.; Muller, T. J. J. Chem.;Eur. J. 2008, 14,
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Muller, T. J. J.; Bunz, U. H. F. J. Org. Chem. 2007, 72, 6714. (d) Lai,
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r
10.1021/ol402350x
XXXX American Chemical Society