ORGANIC
LETTERS
2009
Vol. 11, No. 6
1193-1196
A New and Facile Synthesis of
Quinazoline-2,4(1H,3H)-diones
Li Jiarong,* Chen Xian, Shi Daxin, Ma Shuling, Li Qing, Zhang Qi, and
Tang Jianhong
School of Chemical Engineering and EnVironment, Beijing Institute of Technology,
Beijing, P. R. China 100081
Received October 23, 2008
ABSTRACT
A new and facile preparation of quinazoline-2,4(1H,3H)-diones was first reported which was the condensation of aromatic o-aminonitriles with
DMF or N,N-diethylformamide in the presence of ZnCl2 (0.5-10 mol %) at 190-200 °C in the sealed reactor.
In recent decades, quinazoline-2,4(1H,3H)-diones have drawn
the attention of chemists and medicinal chemists because of
their various biological activities for use as R-adrenergic
receptor antagonists,1 anticonvulsants,2 antibacterial,3 psy-
chosedative,4 antihypertensive,5 or hypotensive compounds,
or inhibitors of puromycin-sensitive aminopeptidase.6 Quinazo-
line-2,4(1H,3H)-diones are also useful synthetic materials
in heterocyclic chemistry.7 There are a number of synthetic
methods available for the preparation of quinazoline-
2,4(1H,3H)-diones. o-Amino-benzoic acid or its derivatives,8
o-aminobenzonitrile,9 isatoic anhydride,10 o-azidobenzoic
acid,11 halobenzoic acid and its ester,12 2-carbomethoxyphe-
nyl isocyanate,13 N-arylnitrilium salts,14 and 4H-3,1-ben-
zoxazinone15 are common starting materials for their prepa-
ration. Some environmental benign methods such as solid-
phase synthesis are also used for preparation of quinazoline-
2,4(1H,3H)-diones.16 Recently, Mizuno, et al.17 described a
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10.1021/ol900093h CCC: $40.75
Published on Web 02/24/2009
2009 American Chemical Society