1

Antimony trichloride, an efficient and mild catalyst for

cyclization of 2-aminochalcones to the corresponding
2-aryl-2, 3-dihydroquinolin-4-(​1H​)-ones.

R. N. Bhattacharya, Pradip Kundu and Gourhari Maiti

Department of Chemistry, Jadavpur University, Jadavpur,

Kolkata 700 032, India

Abstract: Antimony trichloride is found to be an efficient catalyst for the cyclization of 2-amino
chalcones to the corresponding 2-aryl-2, 3-dihydroquinolin-4-(​1H​)-ones under mild reaction
condition and in almost quantitative yields.

Keywords:

INTRODUCTION

2-Aryl-2,3-dihydroquinolin-4-(​1H​)-ones bearing substituents on the aromatic rings are

established as valuable intermediate​1 for the synthesis of medicinally important compounds​2
which are eventually not readily accessible.​2b, 3 General method for their preparation largely
involved the
intramolecular aza-Michael reaction of 2-amino chalcone, bearing
________________________

Address correspondence to Gourhari Maiti, Department of Chemistry, Jadavpur University,

Kolkata 700 032, India. Tel.: 91 33 2414 6223; Fax: 91 33 2414 6223; E-mail:
ghmaiti123@yahoo.co.in

substituents in the aromatic rings catalyzed by either acid or base​4 and also by
microwave-assisted cyclization on solid support such as clay, silica gel and neutral alumina.
Most of the existing procedures involve the use of corrosive reagents such as orthophosphoric
acid, acetic acid or strong alkalis. Furthermore, many of them are of limited synthetic scope due
to low yields, long reaction times and need of large amount of catalyst, specialized solvents​5 or
microwave irradiation with solid support​6 and high temperature on solid support.​7 ​Therefore, the
development of new methods that lead to convenient procedures and better yields are still
desirable.
In continuation to our effort of exploring antimony trichloride (SbCl​3​),​8 as a mild and efficient
catalyst we report herein an efficient method for the synthesis of
2,3-dihydroquinolin-4-(​1H​)-ones through the cyclization of 2-aminochalcones using SbCl​3 in
acetonitrile at 55°C temperature. The salient feature of this methodology includes quantitative
conversion, operational simplicity, inexpensive catalyst, ease of isolation of product, clean
reaction and mild condition. To our knowledge there is no report of exploring this catalyst for
such type of intramolecular aza-Michael reactions. By using very simple experimental
procedures,​9 wide ranges of substituted and structurally diverse 2-aminochalcones were
subjected to cyclization reaction. We carried out the aza-Michael reaction of 2-aminochalcones
in the presence of SbCl​3 (10-30 mol%) at 55°C in dry acetonitrile to furnish the corresponding
2,3-dihydroquinolin-4-(​1H​)-ones in a quantitative yield (Scheme 1).

Thus, a series of 2-aminochalcones with various stereo-electronic effects were subjected to

SbCl​3​-catalyzed cyclization reaction and the results are summarized in Table 1. Structure of the
products were

e stablished from their

spectral analysis (IR, 1​​ H, 13​
​ C NMR and HRMS) and

also by comparison with the literature values.​6b A few other solvents such as dichloromethane,
ethanol, THF were also tested but they required longer reaction time and gave poorer yield
compared to acetonitrile. The reaction was also carried out at room temperature, which required
longer reaction time (48 h) without any side product (Table 1, entry 3). Raising of temperature
from 55​ C to reflux condition has negligible effect on the reaction rate. Electron donating
group in the aromatic ring increases the rate while electron-withdrawing group decreases the rate
of the reaction. However, in case of synthesis of 2-(4​​-nitrophenyl) 2,3-
dihydroquinolinone derivatives, from the corresponding 2-(4​​-nitrophenyl) aminochalcone did
not undergo cyclization to a considerable
extent after heating at 55​ C for 24 h with 30 mol % catalyst loading while 50 % conversion
was noted after left for 7 days at room temperature. It is known that silica gel or neutral alumina
coated with ​p-​ toluene sulphonic acid catalyzes the reaction with relatively low yield, whereas
basic alumina spoils the substrate. Microwave irradiation of montmorillonite K-10 as solid
support​6a and InCl​3 ​on Silica gel,​6b gave good yields of the products, but the said catalyst systems
reported to be less efficient under conventional thermal condition. Although SiO​2​-TaBr​5 at ​ high
7a
temperature (140​ C)​ gave good yields, while TaBr​5 alone in solution gave the product in low
yield (30-40%), even after prolonged reaction time. Very recently, CeCl​3​.7H​2​O. NaI on either
silica gel or alumina support​7b have been reported to afford good yield of products whereas
CeCl​3​.7H​2​O.NaI in refluxing dichloromethane gave only 20-25 % of desired products after three
days of reaction period. Hence, the present study has unequivocally proves that antimony
trichloride acts as a better catalyst in the solution phase for the intramolecular aza-Michael
reaction.
With these encouraging results in hand we also performed the aza-Michael reaction with 10
mol% SbCl​3 on silica gel (60-120 mesh) support (Method B) in four cases were studied [Table 1,
entry, 1 (97 %), 3 (96 %), 10 (98 %), 11 (96 %)] and it was found that the reaction was
completed within 10 minutes on conventional heating at 100​ C in almost quantitative yield. In
case of 2-(4​​-nitrophenyl) aminochalcone, the reaction was completed within 2.5 h at 100​ C
in 95 % yield. So, it can be interpreted that the rate of the reaction is very much dependent on the
electronic nature of the aromatic ring substituents.
T able 1​. ​Antimony
trichloride catalyzed efficient synthesis of 2,3-dihydroquinolin-4(​1H)​ -ones​a
_____________________________________
a​
All reaction were carried out by using SbCl​3​ in acetonitrile at 55​​ C temperature (Method A).
b​
All products were characterized by m.p., IR, NMR, and HRMS data and are agreement with the literature value.
c​
Yield refers to pure isolated products.

In conclusion, we have developed a mild and efficient methodology for the synthesis of
2-aryl-2,3-dihydroquinolin-4-(​1H)​ -ones in solution and under conventional thermal heating
condition on solid silica gel support. Antimony trichloride was found to be the better catalysts in
terms of cost, handling, remarkably operational simplicity and products isolation.
Acknowledgemen​t: P. K. thanks Jadavpur University, Kolkata and Government of West Bengal
for awarding the SRF.

References and Notes

1. (a) Singh, O. V.; Kapil, R. S. Synth. Commun. ​1993​, ​23,​ 277; (b) Prakash, O.; Kumar, D.;
Saini, R. K.; Singh, S. P.​ Synth. Commun.​ ​1994​, ​24,​ 2167.
2. (a) Kalinin, V. N.; Shostakovsky, M. V.; Ponomaryov, A. B. ​Tetrahedron Lett. ​1992​, 33​,
273; (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.
3. (a) Torri, S.; Okumoto, H.; He-Xu, L. T. Tetrahedron Lett. ​1991​, 32​, 237; (b) Homi, O. E.
O.; Peltonen, C.; Heikkila, L.​ J. Org. Chem​. ​1990​, ​55​, 2513.
4. (a) Donnelly, J. A.; Farrell, D. F. ​Tetrahedron Lett. ​1990​, 46​, 885, (b) Donnelly, J. A.;
Farrell, D. F. ​J. Org. Chem​. ​1990​, ​55​, 1757; (c) Tokes, A. L.; Litkei, G. ​Synth. Commun. 1​ 993​,
23​, 895.
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) Verma, R. S.; Saini, R. K. ​Synlett ​1997​, 857; (b) Kumar, K. H.; Muralidharan , D.,
Perumal, P. T. ​Synthesis​ ​2004​, 63.
7. (a) Ahmed, N.; van Lier, J. E. ​Tetrahedron Lett. ​2006​, 47, 2725; (b) Ahmed, N.; van Lier, J.
E. Tetrahedron Lett. ​2006​, ​47,​ 5345; (c) Ahmed, N.; van Lier J. E. ​Tetrahedron Lett.​ ​2007​, 48,
13 and reference cited theirin
8. (a) Maiti G.; Kundu , P. ​Tetrahedron Lett. ​2006​, ​47​, 5733, (b) Maiti, G.; Kundu, P. ​Synth.
Commun. ​2007​, ​47​, 5733.
9. ​General procedure​: (Method A): To a stirred solution of 2-amino chalcone, ​1i (303 mg, 1.0
mmol) in acetonitrile 1.0 mL was added solid antimony trichloride (68 mg, 0.3 mmol). The
reaction mixture was heated at 50-55​ C for 3.5 h (completion was monitored by TLC). The
reaction mixture was decomposed with 5 mL water and extracted with dichloromethane 2X15
mL, washed with brine solution (5 mL) and dried over anhydrous Na​2​SO​4​. Volatiles were
removed and the crude residue was purified by short column chromatography using 10 % ethyl
acetate -petroleum ether as eluent to afford ​2i solid (297 mg, 98 %). mp 126​ C; 1​​ H NMR (300
MHz, CDCl​3​) ​ 2.74 (dd, ​J = ​ 12.6, 16.3 Hz, 1H), 2.95 (dd, ​J ​= 3.9, 16.3 Hz, 1H), 4.58 (s, 1H),
5.20 (dd, ​J ​= 3.9, 12.5 Hz, 1H), 6.74 (d, ​J ​= 8.2 Hz, 1H), 6.80 (t, ​J =​ 7.7 Hz, 1H), 7.19 (dt, ​J =
​
1.5, 7.7 Hz, 1H), 7.32-7.39 (m, 2H), 7.58 (d, ​J ​= 8.0 Hz, 1H), 7.68 (dd, ​J ​= 1.3, 7.8 Hz, 1H), 7.88
 ​ 7.9 Hz, 1H); 13​
(d, ​J = ​ C NMR (75 MHz, CDCl​3​) ​ 44.2, 56.8, 116.1, 118.7, 119.1, 122.9, 127.6,
127.7, 128.2, 129.7, 133.3, 135.5, 139.9, 151.5, 192.8.; HRMS calcd for [C​15​H​12​NBrO + Na​+​]
323.9999, found 324.0032.
  Spectral data of ​2k​: mp 92​​C, 1​​ H NMR (300 MHz, CDCl​ ) ​ 2.92 (dd, ​J ​= 5.4, 16.1 Hz, 1H),
3​
3.00 (dd, ​J ​= 9.8, 16.3 Hz, 1H), 4.79-4.84 (m, 2H), 6.25 (d, ​J = ​ 3.2 Hz, 1H), 6.32 (m, 1H), 6.70
(d, ​J =​ 8.3 Hz, 1H), 6.76 (t, ​J ​= 5.9 Hz, 1H), 7.31 (dt, ​J =
​ 1.5, 7.3 Hz, 1H) 7.37 (s, 1H), 7.84 (dd,
J ​= 1.2, 7.9 Hz, 1H); 13​​ C NMR (75 MHz, CDCl​3​) ​ 441.9, 50.7, 106.8, 110.3, 116.0, 118.5,
119.1, 127.3, 135.4, 142.4, 150.4, 153.3, 192.6; HRMS calcd for [C​13​H​11​NO​2 + Na​+​] 236.0687,
found 236.0685.
General procedure​: (Method B): A solution of 2-aminochalcone (​1j​) (121 mg, 0.5 mmol) in 0.5
mL of acetonitrile was added to silica gel impregnated with SbCl​3 (12 mg, 0.05 mmol) prepared
by adding a solution of SbCl​3 in acetonitrile (2 mL) to silica gel (200 mg, 60-120 mesh),
followed by evaporation of the solvent in vacuum. The reaction mixture was heated at 100​ C
for 10 min. and on completion, the reaction mixture was directly charged onto a small silica gel
column (10 % ethyl acetate-petroleum ether) to afford the pure product ​2j (118 mg, 98 %). M.p.
134 ​​C; 1​​ H NMR (300 MHz, CDCl​3​): ​ 2.67-2.85 (m, 2H), 4.64 (s, 1H), 4.70 (dd, ​J ​= 4.3, 13.2
Hz, 1H), 6.74 (d, ​J =​ 8.5 Hz, 1H), 6.79 (d, ​J ​= 8.5 Hz, 1H), 7.06 (t, ​J ​= 8.6 Hz, 2H), 7.34 (dt, ​J ​=
1.4, 7.7 Hz, 1H), 7.41 (dd, ​J = ​ 5.4, 8.6 Hz, 2H), 7.84 (d, ​J ​= 7.9 Hz, 1H); 13​
​ C NMR (75 MHz,
CDCl​3​): ​ 46.5, 57.8, 115.7, 116.0 (2), 118.6, 119.0, 127.6, 128.3, 128.4, 135.5, 136.8, 136.9,
151.5, 193.1.
Graphical abstract

Antimony Trichloride, an Efficient and Mild Catalyst for the Cyclization of

2-Amino Chalcones to the Corresponding 2-Aryl-2,3-dihydro -4-(​1H)​ -ones.

R. N. Bhattacharya, Pradip Kundu and Gourhari Maiti

 Justification for publication in Synth. Commun.

2-Aryl-2,3-dihydroquinolin-4(​1H​)-ones bearing substituents on the aromatic rings are

established as valuable intermediate for the synthesis of medicinally important compounds which
are eventually not readily accessible. General method for their preparation largely involved the
intramolecular aza-Michael reaction of 2-amino chalcone, bearing substituents in the aromatic
rings catalysed by either acid or base and also by microwave-assisted cyclisation on solid support
such as clay, silica gel and neutral alumina. Most of the existing procedures involve the use of
corrosive reagents such as orthophosphoric acid, acetic acid or strong alkalis. Furthermore, many
of them are of limited synthetic scope due to low yields, long reaction times and need of large
amount of catalyst, specialized solvents or solid support and microwave irradiation and high
temperature on solid support. From the earlier report it was found that silica gel or neutral
alumina coated with ​p-​ toluene sulphonic acid catalyses the reaction with relatively low yield,
whereas basic alumina completely destroy the substrate. Recently reported method using
Microwave irradiation of montmorillonote K-10 as solid support and InCl​3 on ​ Silica gel, etc.
gave good yields, but these catalyst systems were less efficient under conventional heating
condition. Although SiO​2​-TaBr​5 at
​ high temperature (140​0​C) gave good yields, while TaBr​5 alone
in solution gave the product in low yield (30-40%), even after prolong reaction times of 3h. Very
recently, CeCl​3​.7H​2​O.NaI on either silica gel or alumina support afford good yield of products
whereas CeCl​3​.7H​2​O.NaI in refluxing dichloromethane solvent gave only 20-25% of desired
products after three days of reaction period. Hence the present study has unequivocally
confirmed that antimony trichloride is a better catalyst in the solution phase as well as on solid
support for the intramolecular aza-Michael reaction.
The reactions were very clean and products were obtained in excellent yields without the
formation of side products. The reaction conditions are mild, ease of handling, excellent yield
and efficient. Considering the efficiency of this methodology we think that it should be published
in ​Synthetic Communications.

(G. Maiti)