Alumina supported-CeCl3·7H2O-NaI: an efficient catalyst for the 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.2006.11.020

We recently advanced silica gel supported-TaBr₅ as an efficient catalyst for the isomerization of 2′-aminochalcones to the corresponding 2-aryl-2,3-dihydroquinolin-4(1H)-ones under solvent free conditions (Tetrahedron Lett. 2006, 47, 2725-2729)

Full text of DOI:10.1016/j.tetlet.2006.11.020

Tetrahedron Letters 48 (2007) 13–15
Alumina supported-CeCl Æ7H O–NaI: an efficient catalyst for
3
2
0
the cyclization of 2 -aminochalcones to the corresponding
-aryl-2,3-dihydroquinolin-4(1H)-ones under solvent free conditions
2
Naseem Ahmed and Johan E. van Lier*
Department of Nuclear Medicine and Radiobiology, Faculty of Medicine and Health Sciences, Universit e´ de Sherbrooke,
Sherbrooke, Que., Canada J1H 5N4
Received 28 September 2006; revised 1 November 2006; accepted 2 November 2006
0
Abstract—We recently advanced silica gel supported-TaBr
5
as an efficient catalyst for the isomerization of 2 -aminochalcones to the
corresponding 2-aryl-2,3-dihydroquinolin-4(1H)-ones under solvent free conditions (Tetrahedron Lett. 2006, 47, 2725–2729). This
conversion can be further improved through the use of more economic alumina supported-CeCl Æ7H O–NaI, providing high yields
3
2
of up to 98% at lower reaction temperatures. This stable catalyst is easily prepared, active under solvent-free conditions and
employed under environmentally friendly conditions.
Ó 2006 Elsevier Ltd. All rights reserved.
2
-Aryl-2,3-dihydroquinolin-4(1H)-ones substituted on
several heterogeneous catalysts have also been evaluated
and excellent results have been achieved.
1
9
the aromatic rings are valuable precursors for the syn-
thesis of medicinally important compounds. Generally,
2
their synthesis is carried out using acid or base catalyzed
We recently reported that silica gel supported-TaBr is
an efficient catalyst for the isomerization of 2 -amino-
5
0
0
isomerization of substituted 2 -aminochalcones via the
3
aza-Michael reaction. Many of the existing procedures
chalcones to the corresponding 2-aryl-2,3-dihydroquin-
1
0
are of limited synthetic scope due to low yields, long
reaction times and the need for large amount of catalyst,
olin-4(1H)-ones under solvent free conditions. In a
search for a more economic catalyst showing high
activity under mild reaction conditions, we evaluated
alumina supported-KF (Aldrich–Fluka) as well as silica
and alumina supported-CeCl Æ7H O–NaI. Particularly
4
5
specialized solvents or microwave activation. The Mi-
chael addition reaction has found many applications for
carbon–carbon and carbon–heteroatoms bond forma-
3
2
6
tion in the presence of acid or base catalysts. To avoid
the latter provided high yields at low reaction tempera-
tures for the intramolecular aza-Michael cyclization of
aminochalcones to flavonones. This stable catalyst is
typical disadvantages like polymerization of enones (Mi-
chael acceptors) resulting from the presence of acid and
base catalysts, a number of alternative procedures have
been developed including various Lewis acid-induced
7
alumina supported -
reactions. Particularly, the conjugate addition of nitro-
.
CeCl3 7H O - NaI
2
gen nucleophiles (Michael donors through intermole-
cular or intramolecular attack) to the a,b-unsaturated
carbonyl compounds (aza-Michael reaction) is notewor-
7
0 oC, 2 - 2.5 h, 98%
O
O
silica gel supported -
CeCl .7H O - NaI
8
thy due to its simplicity, economy, and atom efficiency.
3
2
With the aim to further improve the reaction’s efficiency,
70 o
NH2
C, 2 - 2.5 h, 80%
N
H
2
1
alumina supported / KF
0
Keywords: Alumina and silica gel supported-CeCl
3
Æ7H
2
O–NaI; 2 -
Aminochalcones; Aza-Michael reaction; 2-Aryl-2,3-dihydroquinolin-
4
*
(1H)-ones.
0 oC, 1-7 days
7
Corresponding author. Tel.: +1 819 564 5409; fax: +1 819 564
5442; e-mail: johan.e.vanlier@USherbrooke.ca
Scheme 1.
0040-4039/$ - see front matter Ó 2006 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2006.11.020

14
N. Ahmed, J. E. van Lier / Tetrahedron Letters 48 (2007) 13–15
0
a
Table 1. Oxidative cyclization of 2 -aminochalcones catalyzed by alumina supported-CeCl
3
2
Æ7H O–NaI
b
c
Entry
Substrate
Product
Yield (%)
H
N
NH2
a
98
98
92
96
96
94
O
O
Br
Br
H
N
NH2
b
c
d
e
f
O
O
H
N
OMe
OMe
NH2
O
O
H
N
Cl
Cl
F
NH2
O
O
F
H
N
NH2
O
O
H
N
NO2
NO
2
NH2
O
O
Cl
Cl
H
N
NH2
g
90
Cl
Cl
O
O
MeO
NH2
MeO
H
N
O
h
86
85
OMe
OMe
O
OMe
OMe
H
Br
NH2
O
Br
N
i
O
MeO
NH2
MeO
H
Br
Br
Br
Br
Br
Br
N
j
84
84
83
OMe
OMe
O
O
NO2
NO2
H
N
NH2
k
O
O
Cl
Cl
H
NH2
N
l
Cl
Cl
O
O
a
b
c
Reaction conditions: Substrate (1.0 mmol) and alumina supported-CeCl
3 2
Æ7H O–NaI (300–400 mg) were kept at 70 °C for 2–2.5 h.
Isolated and non-optimized yield.
1
13
10a
Identification of the products was ascertained by H- and C NMR, mass spectroscopy and by comparison with published values.

N. Ahmed, J. E. van Lier / Tetrahedron Letters 48 (2007) 13–15
15
easily prepared, active under solvent-free conditions and
employed under environmentally friendly conditions.
Acknowledgment
1
1
This work was supported by the Canadian Institutes of
Health Research (CIHR, Grant MOP- 44065).
1
1c
The experimental procedure
2
consists of absorbing
0
-aminochalcone (1) on neutral alumina or silica gel
catalysts (3.5 mol %
CeCl Æ7H O), heating the reaction mixture for 2–2.5 h
at 70 °C followed by extraction to give the 2-aryl-2,3-
dihydroquinolin-4(1H)-ones (2) in high yield (Scheme
). Using basic conditions, as in the case of alumina sup-
ported-KF, failed to give the desired product, which is
likely due to complete decomposition of the substrate.
To test the general applicability of neutral alumina sup-
supported-CeCl Æ7H O–NaI
3
2
3
2
References and notes
1
. (a) Prakash, O.; Kumar, D.; Saini, R. K.; Singh, S. P.
Synth. Commun. 1994, 24, 2167–2172; (b) Singh, O. V.;
Kapil, R. S. Synth. Commun. 1993, 23, 277–283.
1
9
a
2. (a) Kalinin, V. N.; Shostakovsky, M. V.; Ponomaryov, A.
B. Tetrahedron Lett. 1992, 33, 373–376; (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,
1155–1162.
0
ported-CeCl Æ7H O–NaI as a catalyst for 2 -aminochal-
3
2
cone cyclization, a wide range of substrates were treated
as described above.1 The resulting 2-aryl-2,3-dihydro-
quinolin-4(1H)-ones were obtained in excellent yields
Table 1); the assigned structures were confirmed by
their spectral properties (IR, H- and C NMR, and
MS) and by comparison with literature data. The rel-
ative long reaction time (2–2.5 h) likely reflects the low
nucleophilicity of the aromatic amines and could not
be improved upon by increasing the reaction tempera-
ture. Neither CeCl Æ7H O nor NaI alone could induce
the reaction even after 7 days incubation. However,
using CeCl Æ7H O–NaI (3.5 mol %) in CH Cl at reflux
gave 20–25% of the desired product after a 3 day reac-
tion period. Furthermore, omitting NaI in the alumina
or silica gel–CeCl Æ7H O preparation resulted in com-
plete loss of catalytic activity. NaI likely induces ha-
lide-exchange resulting in enhanced Lewis acid activity
of CeCl Æ7H O, which in turn is essential for its catalytic
activity. Our data show that alumina supported-
CeCl Æ7H O–NaI is a more efficient catalyst for the
intramolecular aza-Michael cyclization reaction as
compared to recently reported methods using
1
3
. (a) Donnelly, J. A.; Farrell, D. F. J. Org. Chem. 1990, 55,
1
757–1761; (b) Tokes, A. L.; Litkei, Gy. Synth. Commun.
(
1
993, 23, 895–902, and references cited therein.
1
13
4
. (a) Tokes, A. L.; Szilagyi, L. Synth. Commun. 1987, 17,
235–1245; (b) Tokes, A. L.; Litkei, Gy.; Szilagyi, L.
Synth. Commun. 1992, 22, 2433–2445.
1
0a
1
5. (a) Kumar, K. H.; Muralidharan, D.; Perumal, P. T.
Synthesis 2004, 63–68; (b) Varma, R. S.; Saini, R. K.
Synlett 1997, 857–858.
3
2
6
. (a) Hong, S.; Marks, T. J. Acc. Chem. Res. 2004, 37, 673–
86; (b) Muller, T. E. Chem. Rev. 1998, 98, 675–704.
6
3
2
2
2
7
8
. Christoffers, J. Eur. J. Org. Chem. 1998, 1259–1266.
. (a) Xu, L. W.; Li, L.; Xia, C. G. Tetrahedron Lett. 2004,
4
5
5, 4507–4510; (b) Liu, M.; Sibi, M. P. Tetrahedron 2002,
8, 7791–8035; (c) Cardillo, G.; Tomasini, C. Chem. Soc.
3
2
Rev. 1996, 117–128.
9
. (a) Loh, T. P.; Wei, L. L. Synlett 1998, 975–976; (b)
Bartoli, G.; Bartolacci, M.; Guiliani, A.; Marcantoni, E.;
Massimo, M.; Torregiani, E. J. Org. Chem. 2005, 70, 169–
175.
3
9
2
b
3
2
1
0. (a) Ahmed, N.; van Lier, J. E. Tetrahedron Lett. 2006, 47,
725–2729, and references cited therein; (b) Ahmed, N.;
2
5
b
van Lier, J. E. Tetrahedron Lett. 2006, 47, 5345–5349; (c)
Ahmed, N.; Ansari, W. H. J. Chem. Res. (S) 2003, 9, 572–
microwave irradiation on montmorillonite K 10 clay
or silica gel impregnated InCl3.
5
a
5
73; (d) Ahmed, N.; Ali, H.; van Lier, J. E. Tetrahedron
Lett. 2005, 46, 253–256.
1. (a) Preparation of neutral alumina supported CeCl Æ7H O–
3 2
0
We also subjected 2 -hydroxychalcones (3) to the same
reaction conditions but failed to detect the correspond-
ing flavonones (4), even after prolonged reaction times
of 3 days (Scheme 2). This lack of reactivity may be
due to the low nucleophilicity of oxygen in 3 as com-
pared to the amino nitrogen in 1.
1
NaI: Neutral alumina (1.35 g) (BIO-RAD, Brockman
activity, grade I, 2–44 lm) was added to a stirred mixture
of CeCl Æ7H O (0.68 g, 1.82 mmol) and NaI (0.23 g,
3 2
1.55 mmol) in MeCN (10 mL) and further stirred over-
night. The acetonitrile was evaporated on a rotary
evaporator and the resulting powdered catalyst was stored
under argon for future use. (b) Preparation of silica gel
In conclusion, we have shown that different 2-aryl-2,3-
dihydroquinolin-4(1H)-ones can easily be prepared from
their 2 -aminochalcone precursors in high yield under
solvent free conditions, using neutral alumina sup-
supported-CeCl
3 2
Æ7H O–NaI: Silica gel (1.26 g) (EM Sci-
ence Germany, 60A, 70–230 mesh), CeCl Æ7H O (1.0 g,
0
3
2
2
(
.72 mmol) and NaI (0.34 g, 2.32 mmol) in MeCN
10 mL), followed by the above procedures gave powdered
catalyst that was stored under argon for further use. (c)
ported-CeCl Æ7H O–NaI as a catalyst. The advantage
3
2
0
0
of this procedure over earlier reported processes in-
cludes simplicity, low reaction temperature, high yield,
absence of secondary products, and organic solvent-free
conditions.
General procedure for cyclization of 2 -aminochalcones: 2 -
Aminochalcone (1.0 mmol) was dissolved in CH Cl (1–
1.5 mL) and alumina supported CeCl Æ7H O–NaI (300–
00 mg) or silica gel supported catalyst (300–400 mg) was
2
2
3
2
4
added. The solvent was evaporated by heating and the
resulting powdered reaction mixture was further heated
for an additional 2–2.5 h at 70 °C. After completion of the
reaction (by TLC monitoring), the mixture was cooled to
rt and the product was recovered by washing with diethyl
ether and solvent evaporation. Alternatively the reaction
mixture was directly applied on a silica gel column and
eluted with hexane:CH Cl (1:9) to afford the pure
O
alumina supported /
O
.
CeCl3 7H O - NaI
2
OH
3
0 oC, 1 - 3 days
O
7
4
2
2
Scheme 2.
products (Table 1).