Silica gel supported TaBr5: New catalyst for the facile and rapid cyclization of 2′-aminochalcones to the corresponding 2-aryl-2,3-dihydroquinolin-4(1H)-ones under solvent-free conditions

Article abstract of DOI:10.1016/j.tetlet.2006.02.086

Silica gel supported TaBr₅ (5-10 mol %) is a new solid-support catalyst that can be used under solvent-free conditions for the facile and efficient isomerization of 2′-aminochalcones to the corresponding 2-aryl-2,3-dihydroquinolin-4(1H)-ones. The catalyst is easily prepared, stable and employed under environmentally friendly conditions.

Full text of DOI:10.1016/j.tetlet.2006.02.086

Tetrahedron Letters 47 (2006) 2725–2729
Silica gel supported TaBr5: new catalyst for the facile and
rapid cyclization of 20-aminochalcones to the corresponding
2-aryl-2,3-dihydroquinolin-4(1H)-ones under solvent-free conditions
Naseem Ahmed and Johan E. van Lier*
Department of Nuclear Medicine and Radiobiology, Faculty of Medicine, Universite´ de Sherbrooke, Sherbrooke,
Que´bec, Canada J1H 5N4
Received 4 November 2005; revised 14 February 2006; accepted 15 February 2006
Available online 3 March 2006
Abstract—Silica gel supported TaBr5 (5–10 mol %) is a new solid-support catalyst that can be used under solvent-free conditions for
the facile and efficient isomerization of 20-aminochalcones to the corresponding 2-aryl-2,3-dihydroquinolin-4(1H)-ones. The catalyst
is easily prepared, stable and employed under environmentally friendly conditions.
ꢀ 2006 Elsevier Ltd. All rights reserved.
2-Aryl-2,3-dihydroquinolin-4(1H)-ones substituted on
the aromatic rings are valuable precursors1 for the syn-
thesis of medicinally important compounds,2 which are
often not readily accessible by other means.2a,3 The for-
mation of 2,3-dihydroquinolin-4(1H)-ones is generally
accomplished by acid- or base-catalyzed isomerization
of substituted 20-aminochalcones.4 Most of the proce-
dures involve the use of corrosive reagents such as
orthophosphoric acid, acetic acid or strong alkali. Fur-
thermore, many of them are of limited synthetic scope
due to low yields, long reaction times and the need for
large amount of catalyst, specialized solvents5 or micro-
wave activation.6 As a continuation of our interest in
solid-support reactions,7 we evaluated the synthesis of
2,3-dihydroquinolin-4(1H)-ones (2) from 20-aminochal-
cones (1) using tantalum bromide (TaBr5) under
solvent-free conditions. The salient features of TaBr5
impregnated on silica gel are rapid reaction rates, ab-
sence of unwanted products, improved and operational
simplicity under conventional heating.
metal halide catalysts such as TiX4AlX3, ZnX2ZrX4 and
SnX4.9 It was also shown that metal bromides act as
better Lewis acids in many organic syntheses as com-
pared to their chloride counter part, for example,
InBr3 > InCl3, ZnBr2 > ZnCl2.7b In-depth studies on
the Lewis acid catalyzed reactions of tantalum halides
revealed that TaBr5 adsorbed on silica gel has better
catalytic properties than TaBr5 in solution, due to the
increase in tantalum oxophilicity.10 The high efficacy
of this catalyst and ease of product isolation prompted
us to investigate its use for the synthesis of the 2-aryl-
2,3-dihydroquinolin-4(1H)-ones (2). To our knowledge,
no studies exploiting this catalyst for such cyclization
reactions have previously been reported (Scheme 1).
Using a simple experimental procedure,11 a wide range of
substituted 20-aminochalcones (1) adsorbed on silica gel
supported TaBr5 were heated for 3–5 min at 140–150
ꢁC, which gave 2-aryl-2,3-dihydroquinolin-4(1H)-ones
In recent years, TaX5 (X = Cl, Br) have been used as
Lewis acids in various organic syntheses.8 In many
cases, these metal halides are reported to be more effi-
cient catalysts and easier to handle as compared to other
O
O
Silica gel supported TaBr5
140 - 150 oC, 3 - 5 min.
NH2
N
H
2
1
Keywords: Silica gel supported TaBr5; 20-Aminochalcones; Michael
addition reaction; 2-Aryl-2,3-dihydroquinolin-4(1H)-ones.
Scheme 1. Synthesis of 2-aryl-2,3-dihydroquinolin-4(1H)-ones (2)
using silica gel supported TaBr5 under solvent-free conditions (overall
yield 90–95%, vs 30–40% after 3 h in TaBr5-solution).
*
Corresponding author. Tel.: +1 819 564 5409; fax: +1 819 564
5442; e-mail: johan.e.vanlier@USherbrooke.ca
0040-4039/$ - see front matter ꢀ 2006 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2006.02.086

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N. Ahmed, J. E. van Lier / Tetrahedron Letters 47 (2006) 2725–2729
Table 1. Silica gel supported TaBr5 mediated oxidative cyclization of 20-aminochalcones and 20-hydroxychalcones
Entry
Substrate
Product
Yield (%)a,b,c
H
N
NH2
a
92
O
O
Br
Br
H
N
NH2
b
86
O
O
OMe
OMe
H
N
NH2
O
c
80
O
Cl
Cl
H
N
NH2
O
d
80
O
F
F
H
N
NH2
e
83
75
O
O
NO2
NO2
H
N
NH2
f
O
O
Cl
Cl
H
N
NH2
g
82
Cl
Cl
O
O
MeO
NH2
MeO
H
N
h
70
75
OMe
OMe
O
O
OMe
OMe
H
Br
NH2
Br
N
i
O
O

N. Ahmed, J. E. van Lier / Tetrahedron Letters 47 (2006) 2725–2729
2727
Table 1 (continued)
Entry
Substrate
Product
Yield (%)a,b,c
MeO
NH2
MeO
H
Br
Br
Br
N
j
70
OMe
OMe
O
O
NO2
NO2
H
N
Br
Br
NH2
k
72
75
O
O
Cl
Cl
H
N
NH2
Br
l
Cl
Cl
O
O
Cl
OH
Cl
O
O
m
12d
Cl
Cl
O
OMe
OMe
MeO
O
MeO
OH
O
n
10d
OMe
OH
OMe
O
OMe
OMe
O
o
p
20d
O
O
O
OH
30d
O
O
a Substrate (1.0 mmol), silica gel (200 mg) and TaBr5 (10 mg, 5–10 mol %) were stirred for 3–5 min with heating at 140–150 ꢁC.
b Isolated and non-optimized yield.
c
Identification of the products was ascertained by 1H and 13C NMR, mass spectroscopy and by comparison with available physical and spectro-
scopic data.
d Based on reactant recovered after >72 h.
(2) in high yields (Table 1). The structures of the prod-
coated with p-toluenesulfonic acid also catalyzed these
reactions in relative low yields, whereas basic alumina
completely destroyed the substrates.12 Recently reported
methods using microwave irradiation on montmorillon-
ucts were established from their spectral properties
1
(IR, H and 13C NMR, and MS) and also by compari-
son with available literature data. These reactions did
not occur in the presence of silica gel alone, while TaBr5
in solution in the absence of silica gel gave the products
in low yield (30–40%), even after prolonged reaction
times of 3 h. Similarly, it has been reported that silica
gel or other solid supports such as neutral alumina,
ite K10 clay6b or silica gel impregnated InCl3 as solid
6a
support gave good yields. Again, these supports were
found less efficient under conventional thermal heating.
This confirms that TaBr5 plays an important Lewis acid
role in our silica gel supported cyclization reaction.

2728
N. Ahmed, J. E. van Lier / Tetrahedron Letters 47 (2006) 2725–2729
3. (a) Torii, S.; Okumoto, H.; HeXu, L. Tetrahedron Lett.
O
O
1991, 32, 237; (b) Hormi, O. E. O.; Peltonen, C.; Heikkila,
L. J. Org. Chem. 1990, 55, 2513.
4. (a) Donnelly, J. A.; Farrell, D. F. Tetrahedron 1990, 46,
885; (b) Donnelly, J. A.; Farrell, D. F. J. Org. Chem. 1990,
55, 1757; (c) Tokes, A. L.; Litkei, Gy. Synth. Commun.
1993, 23, 895, and references cited therein.
OH
O
3
4
5. (a) Tokes, A. L.; Szilagyi, L. Synth. Commun. 1987, 17,
1235; (b) Tokes, A. L.; Litkei, Gy.; Szilagyi, L. Synth.
Commun. 1992, 22, 2433.
6. (a) Kumar, K. H.; Muralidharan, D.; Perumal, P. T.
Synthesis 2004, 63; (b) Varma, R. S.; Saini, R. K. Synlett
1997, 857.
Scheme 2. Attempted cyclization of 3 to 4, using silica gel supported
TaBr5 under solvent-free conditions (3–4 min, 140–150 ꢁC), resulted in
substrate decomposition. Prolonged heating at lower temperature
(72 h, 60–70 ꢁC) gave 4 in 10–30% yield.
7. (a) Ahmed, N.; Ansari, W. H. J. Chem. Res. (S) 2003, 9,
572; (b) Ahmed, N.; Ali, H.; van Lier, J. E. Tetrahedron
Lett. 2005, 46, 253.
We also tried to cyclize 20-hydroxychalcones (3) to their
corresponding flavanones (4) using TaBr5 on silica gel
support under similar reaction conditions (Scheme 2).
8. (a) Shibata, I.; Nose, K.; Sakamoto, K.; Yasuda, M.;
Baba, A. J. Org. Chem. 2004, 69, 2185; (b) Shibata, I.;
Kano, T.; Kanazawa, N.; Fukuoka, S. Angew. Chem., Int.
Ed. 2002, 41, 1389; (c) Chandrasekhar, S.; Ramachandar,
T.; Shyamsunder, T. Indian J. Chem. 2004, 43B, 813; (d)
Kirihara, M.; Harano, A.; Tsukiji, H.; Takizawa, R.;
Uchiyama, T.; Hatano, A. Tetrahedron Lett. 2005, 46,
6377; (e) Chandrasekhar, S.; Prakash, S. J.; Jaga-
deshwar, V.; Narsihmulu, Ch. Tetrahedron Lett. 2001,
42, 5561.
The reaction gave a mixture of flavanone and flavone to-
gether with other unidentified products. However, the
same reaction mixture when kept at 60–70 ꢁC in dichlo-
romethane for 72 h gave 4 in 10–30% yields, depending
on the substituants present on the aromatic rings (Table
1). It has been reported that 20-hydroxychalcones 3 on
silica gel supported BiCl3 gave the corresponding flavo-
nones 4 in good yield at lower temperature (60–70 ꢁC).7a
Accordingly, TaBr5 on silica gel is less efficient for the
isomerization of 20-hydroxychalcones 3 as compared to
the cyclization of 20-aminochalcones 1. Presumably,
the mechanism of the latter reaction involves the heat-
facilitated intramolecular Michael addition6a of the ami-
no group to the a,b-unsaturated ketone, whereby the
essential configuration of both the TaBr5 catalyst and
the substrate is secured by their attachment to the silica
gel matrix.
9. Guo, Q.; Miyaji, T.; Hara, R.; Shen, B.; Takahashi, T.
Tetrahedron 2002, 58, 7327.
10. Howarth, J.; Gillespie, K. Tetrahedron Lett. 1996, 37,
6011.
11. General procedure: TaBr5 (5–10 mol %) was added to a
stirred solution of 20-aminochalcones13 (1.0 mmol) in
dichloromethane (1–1.5 mL) under argon and further
stirred for 10 min to complete dissolution. Then, dried
silica gel14 (200 mg) was added and solvent was evapo-
rated. The reaction mixture was heated with stirring for 3–
5 min at 140–150 ꢁC. After cooling, the silica gel was
extracted with diethyl ether, filtered and the solvent
evaporated in vacuo. Products were purified by silica gel
column chromatography using hexane–diethyl acetate (9:1
to 4:1) as eluent. (entry g). (2-(2,6-Dichlorophenyl)-2,3-
dihydroquinolin-4(1H)-one): yellow semi-solid; IR
(CHCl3): 3310 (NH), 1640 cmꢀ1 (C@O); 1H NMR
(CDCl3, 300 MHz): d 7.90 (dd, J = 9.6, 1.6 Hz, 1H),
7.45–7.10 (m, 4H), 6.79 (t, J = 8.0, 1.0 Hz, 1H), 6.68 (d,
J = 8.1 Hz, 1H), 5.78 (dd, J = 4.0, 12.2 Hz, 1H), 4.67 (br s,
1H, NH), 2.66 (dd, 12.2, 4.0 Hz, 2H); 13C NMR (CDCl3,
75.46 MHz): 193.0, 151.7, 138.4, 135.5, 132.8, 130.0, 129.4,
127.6, 127.5, 119.0, 118.6, 116.2, 54.2, 44.1; EIMS: m/z 371
In conclusion, we have shown that 2-aryl-2,3-dihydro-
quinolin-4(1H)-ones 2 can easily be prepared from 20-
aminochalcones 1 in high yield under solvent-free condi-
tion using commercially available tantalum salt and
silica gel. The advantages of this procedure over
earlier reported processes include simplicity, fast and
clean reactions, high yield, and the absence of organic
solvent.
(M+).
(2-(2,6-Dimethoxyphenyl)-2,3-dihydroquinolin-
Acknowledgements
4(1H)-one, entry h): yellow semi-solid; IR (CHCl3): 3280
1
(NH), 1630 cmꢀ1 (C@O); H NMR (CDCl3, 300 MHz): d
7.89 (dd, J = 9.4, 1.5 Hz, 1H), 7.69 (dd, J = 9.4, 1.5 Hz,
1H), 7.31–7.11 (m, 2H), 6.68–6.58 (m, 3H), 5.45 (dd,
J = 4.0, 12.6 Hz, 1H), 4.57 (br s, 1H, NH), 3.81 (s,
2 · OMe, 6H), 2.69 (dd, J = 4.0, 12.6 Hz, 2H); 13C NMR
(CDCl3, 75.46 MHz): 193.5, 152.0, 149.0, 148.6, 136.4,
134.5, 132.8, 128.0, 119.4, 118.64, 116.5, 113.0, 108.6, 56.8,
56.2, 54.2, 46.1; EIMS: m/z 383 (M+). (7-Bromo-2-(4-
nitrophenyl)-2,3-dihydroquinolin-4(1H)-one, entry k): yel-
low solid; mp >250 ꢁC; IR (CHCl3): 3210 (NH),
1628 cmꢀ1 (C@O); 1H NMR (CDCl3, 300 MHz): d 8.29
(dd, J = 9.7, 1.2 Hz, 2H), 7.98 (dd, J = 9.6, 1.2 Hz, 1H),
7.64–7.48 (m, 2H), 7.42 (dd, J = 9.6, 1.6 Hz, 1H), 6.88 (d,
J = 1.6 Hz, 1H), 4.88 (dd, J = 4.3, 12.9 Hz, 1H), 4.57 (br s,
1H, NH), 2.86 (dd, J = 4.3, 12.9 Hz, 2H); 13C NMR
(CDCl3, 75.46 MHz): 193.5, 152.7, 148.4, 145.5, 135.8,
133.4, 132.6, 131.5, 124.5, 122.0, 119.8, 118.6, 58.2, 48.1;
EIMS: m/z 347/345 (M+).
This work was supported by the Canadian Institutes of
Health Research (CIHR, grant MOP-44065).
References and notes
1. (a) Prakash, O.; Kumar, D.; Saini, R. K.; Singh, S. P.
Synth. Commun. 1994, 24, 2167; (b) Singh, O. V.; Kapil, R.
S. Synth. Commun. 1993, 23, 277.
2. (a) Kalinin, V. N.; Shostakovsky, M. V.; Ponomaryov, A.
B. Tetrahedron Lett. 1992, 33, 373; (b) Xia, Y.; Yang, Z.-
Y.; Xia, P.; Bastow, K. F.; Tachibana, Y.; Kuo, S.-C.;
Hamel, E.; Hackl, T.; Lee, K.-H. J. Med. Chem. 1998, 41,
1155; (c) Osawa, T.; Ohata, H.; Akimoto, K.; Harada, K.;
Soga, H.; Jinno, Y. Eur. Pat Appl. EP 343547; Chem.
Abstr. 1990, 112, 235197g.

N. Ahmed, J. E. van Lier / Tetrahedron Letters 47 (2006) 2725–2729
2729
12. (a) Cornelis, A.; Laszlo, P. Synthesis 1985, 909, and
references cited therein; (b) Dellaude, L.; Laszlo, P. J. Org.
Chem. 1996, 61, 6360, and references cited therein.
13. 20-aminochalcones were prepared following the reported
method in Murphy, W. S.; Watanasin, S. Synthesis 1980,
647.
14. Silica gel (60A, 70–230 mesh, EM Science, Germany) dried
for 24 h in the oven (i.e., 120–130 ꢁC) prior to use. If not
dried, a mixture of products or decomposed products is
obtained.