Silica gel supported InBr3 and InCl3: New catalysts for the facile and rapid oxidation of 2′-hydroxychalcones and flavanones to their corresponding flavones under solvent free conditions

Article abstract of DOI:10.1016/j.tetlet.2004.11.062

Silica gel supported InBr₃ or InCl₃ (15-20 mol %) were explored as a new solid-support catalysts for the facile and efficient oxidation, under solvent free conditions, of 2′-hydroxychalcones and flavanones to yield the corresponding flavones in >80% yield. The catalysts are easily prepared, stable, and efficient under mild reaction conditions.

Full text of DOI:10.1016/j.tetlet.2004.11.062

Tetrahedron
Letters
Tetrahedron Letters 46 (2005) 253–256
Silica gel supported InBr3 and InCl3: new catalysts for the facile
and rapid oxidation of 20-hydroxychalcones and flavanones to
their corresponding flavones under solvent free conditions
Naseem Ahmed, Hasrat Ali and Johan E. van Lier*
´
Department of Nuclear Medicine and Radiobiology, Faculty of Medicine, Universite de Sherbrooke, Sherbrooke,
Que, Canada J1H 5N4
Received 3 November 2004; accepted 11 November 2004
Abstract—Silica gel supported InBr3 or InCl3 (15–20mol%) were explored as a new solid-support catalysts for the facile and efficient
oxidation, under solvent free conditions, of 20-hydroxychalcones and flavanones to yield the corresponding flavones in >80% yield.
The catalysts are easily prepared, stable, and efficient under mild reaction conditions.
Ó 2004 Elsevier Ltd. All rights reserved.
Flavones (also known as 2-phenylchromones), consti-
tute a large number of natural products with many
medicinal applications.1 Because of their broad range
of biological activities,2 this class of molecules has been
extensively investigated and more than 4000 chemically
unique flavonoids have been isolated from plants.3
Recently, particular attention has been focused on the
protective biochemical action of naturally occurring
antioxidants and on their mechanism of action. The
phenolic compounds (e.g., flavones) are considered to
play an important role in the prevention of oxidative
damage in living systems.4 Moreover, in capturing free
radicals, their antioxidant activity is highly influenced
by the presence of oxygenated groups (e.g., hydroxy
and methoxy) on the aromatic rings. A large number
of flavonoids are known to exhibit binding affinity and
anti proliferate effects against breast cancer cells in cul-
ture. Previously, we have reported a number of 18F-
labeled estrogen derivatives as possible agents for PET
imaging of breast cancer.5 While evaluating the 18F-
labeling of flavone analogs, we explored methods for
the oxidation of 20-hydroxychalcones and flavanones
to their corresponding flavones, which led to the current
observations.
Among various methods,6a flavones have been synthe-
sized by the oxidation of 20-hydroxychalcones and flav-
anones. Reagents that have been used for this purpose
are SeO2-pentan-1-ol,6c Pd–C/vacuum,7 I2–DMSO,8
SeO2–DMSO,9 DDQ–dioxane,10 NaIO4–DMSO,11
nickel peroxide–dioxane,12 H2O2–NaOH,13 Dowex–2-
propanol,14 SeO2–dioxane,15 SeO2–iso-amyl alcohol,16
Br2–NaOH,17 Tl(NO3)Æ3H2O,18 and I2–triethylene gly-
col.19 Most of these methods are of limited use6 since
yields are low and mixtures of products, containing flav-
ones, flavonones, and aurones are obtained.10,12 Fur-
thermore these procedures require prolonged reaction
times and high temperatures.11,19 Other limitations con-
cern 20-hydroxychalcones possessing a phloroglucinol
oxygenation pattern in ring A.8,9 In the later case a com-
plex mixture was obtained lacking the desired products.
Recently, indium halides have emerged as potential and
efficient catalyst over conventional Lewis acids in pro-
moting various organic transformations,20,21 which led
us to explore these catalysts for the synthesis of flavones.
General procedure for the oxidation of 20-hydroxychal-
cones and flavanones: The 20-hydroxychalcones or flava-
nones (1.0mmol, dissolved in a minimum amount of
ethyl acetate) are added to silica gel supported InBr3
(2.0g, 15–20mol%)23 and the solvent is removed. The
dry mixture is heated with stirring at 130–140°C in an
inert container for different periods of time (Table 1).
The reaction mixture is directly applied on a silica gel
column and eluted with a mixture of ethyl acetate–hex-
ane (1:1). Eluting products are characterized as flavones
Keywords: Silica gel supported InBr3 and InCl3; 20-Hydroxychalcones;
1,4-Cycloaddition; Flavanone; Flavone.
*
Corresponding author. Tel.: +1 819 564 5409; fax: +1 819 564
5442; e-mail: johan.e.vanlier@usherbrooke.ca
0040-4039/$ - see front matter Ó 2004 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2004.11.062

254
N. Ahmed et al. / Tetrahedron Letters 46 (2005) 253–256
Table 1. Silica gel supported InBr3 or InCl3 mediated oxidative cyclization of 20-hydroxychalcones and flavanones to their flavones
Entry
1
Substrate
Time (min)
45
Product
Yield (%)a,b,c
O
OH
96
O
O
O
Cl
Cl
OH
2
45
98
Cl
Cl
O
O
MeO
OH
MeO
O
OMe
OMe
N
3
4
5
6
7
8
45
45
60
55
70
50
95
86
85
90
82
92
O
O
O
N
OH
O
O
O
O
H
OH
OH
O
O
F
F
MeO
HO
O
O
OH
MeO
OMe
O
OMe
O
OH
HO
OH
O
OH
O
B
r
Br
MeO
O
OH
MeO
OMe
O
OMe
OMe
O
MeO
MeO
MeO
MeO
MeO
MeO
O
OH
O
9
45
95
MeO
MeO
O
O
OMe
NO3
NO3
MeO
MeO
OH
10
11
45
45
80
90
O
OMe
OMe
O
O
OMe
OMe
OH
O
OMe
O
OMe
O
O
12
13
120
120
75
65
O
O
OH
OH
O
O
HO
HO
O
OH
O
OH
a Substrate (1.0mmol), silica gel supported InBr3 or InCl3 (2.0g, 15–20mol%) were heated at 130–140°C and stirred for the indicated time.
b Isolated and nonoptimized yield. Conversion based on reactant recovery was 100% except for entries 12 and 13 (75–80%).
1
c Identification of the products was ascertained by H NMR, 13C NMR and mass spectroscopy and compared with Aldrich available spectroscopic
data.

N. Ahmed et al. / Tetrahedron Letters 46 (2005) 253–256
255
based on their spectral properties (1H NMR, 13C NMR,
MS) relative to authentic spectra.24 Using this procedure
a number of substituted chalcone and flavanone deriva-
tives were found to give the corresponding flavones.
Substituents are well tolerated and the products were
obtained in high yield. Using silica gel supported InCl3
under the above conditions the reaction also proceeds
smoothly although overall yields were lower as those ob-
tained with the InBr3 catalyst. This is in accordance with
previous reports on the relative catalytic activities of
these indium halides in the absence of silica gel.25 The
reactions did not occur in the presence of silica gel alone.
Contrary to previously reported methods, this proce-
dure tolerates a wide range of substitutions on the aro-
matic rings of the substrate (Table 1). Generally,
oxidation of substrates with unprotected hydroxyl
groups on the aromatic rings were reported to give poor
yields.1,15,19 However, we found that our new reagent is
equally suitable and efficient for the oxidation of such
derivatives (entries 5, 7, 13). At lower temperature
high yield under solvent free condition using commer-
cially available and inexpensive indium salts and silica
gel. The advantages of this procedure over earlier re-
ported processes include its simplicity, fast and clean
reactions, high yield, and the use of environmentally
friendly catalysts.
Acknowledgements
This work was supported by the Canadian Institutes of
Health Research (CIHR, grant MOP-37768).
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Scheme 1.

256
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amount of ethyl acetate, added dropwise to silica gel (1.0g,
60A, 70–230 mesh, EM Science, Germany) and the slurry
is evaporated to dryness at 80°C. This silica gel supported
InBr3 was kept under argon, and used for 6months
without changing its catalytic activity. InCl3 (14–19mg)
dissolved in a minimum amount of acetonitrile is added to
silica gel (1.0g), evaporated to dryness as above, and
stored under argon for further use.
24. Entry 2, (20, 60-dichloroflavone), mp 146–148°C, 1H NMR
(CDCl3, 300MHz): d 7.48–7.42 (m, 3H), 7.25–7.19 (m,
2H), 7.13 (s, 1H), 6.86 (dd, J = 8.4, 2.1Hz, 1H), 6.65 (dd,
J = 8.4, 2.1Hz, 1H). 13C NMR (CDCl3, 75.46MHz):
103.4, 107.9, 114.2, 116.3, 127.8, 128.9, 132.1, 138.6, 144.6,
154.7, 157.8, 164.2, 183.4. EIMS: m/z 292 (M+) (70%), 257
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