Montmorillonite K10 clay: An effective solid catalyst for one-pot synthesis of polyhydroquinoline derivatives

Article abstract of DOI:10.1080/00397910500297255

An efficient one-pot four-component coupling process for the synthesis of polyhydroquinoline derivatives catalyzed by montmorillonite K10 clay is described. This procedure has such advantages as short reaction time, high yields, and simple workup. The cat

Full text of DOI:10.1080/00397910500297255

This article was downloaded by: [North Carolina State University]
On: 13 April 2013, At: 20:55
Publisher: Taylor & Francis
Informa Ltd Registered in England and Wales Registered Number: 1072954
Registered office: Mortimer House, 37-41 Mortimer Street, London W1T 3JH,
UK
Synthetic Communications: An
International Journal for Rapid
Communication of Synthetic
Organic Chemistry
Publication details, including instructions for
authors and subscription information:
http://www.tandfonline.com/loi/lsyc20
Montmorillonite K10 Clay:
An Effective Solid Catalyst
for One‐Pot Synthesis of
Polyhydroquinoline Derivatives
a b
a b
c
Guoyong Song
, Bo Wang
, Xiaoyin Wu , Yuru
a
a
Kang & Liming Yang
a
State Key Laboratory for Oxo Synthesis and
Selective Oxidation, Lanzhou Institute of Chemical
Physics, Chinese Academy of Sciences, Lanzhou,
China
b
Graduate School of Chinese Academy of Sciences,
Beijing, China
c
College of Earth and Environment Sciences,
Lanzhou University, Lanzhou, China
Version of record first published: 22 Aug 2006.
To cite this article: Guoyong Song , Bo Wang , Xiaoyin Wu , Yuru Kang & Liming Yang
(2005): Montmorillonite K10 Clay: An Effective Solid Catalyst for One‐Pot Synthesis of
Polyhydroquinoline Derivatives, Synthetic Communications: An International Journal
for Rapid Communication of Synthetic Organic Chemistry, 35:22, 2875-2880
To link to this article: http://dx.doi.org/10.1080/00397910500297255
PLEASE SCROLL DOWN FOR ARTICLE

Full terms and conditions of use: http://www.tandfonline.com/page/terms-
and-conditions
This article may be used for research, teaching, and private study purposes.
Any substantial or systematic reproduction, redistribution, reselling, loan,
sub-licensing, systematic supply, or distribution in any form to anyone is
expressly forbidden.
The publisher does not give any warranty express or implied or make any
representation that the contents will be complete or accurate or up to
date. The accuracy of any instructions, formulae, and drug doses should be
independently verified with primary sources. The publisher shall not be liable
for any loss, actions, claims, proceedings, demand, or costs or damages
whatsoever or howsoever caused arising directly or indirectly in connection
with or arising out of the use of this material.

w
Synthetic Communications , 35: 2875–2880, 2005
Copyright # Taylor & Francis, Inc.
ISSN 0039-7911 print/1532-2432 online
DOI: 10.1080/00397910500297255
Montmorillonite K10 Clay: An Effective
Solid Catalyst for One-Pot Synthesis of
Polyhydroquinoline Derivatives
Guoyong Song and Bo Wang
State Key Laboratory for Oxo Synthesis and Selective Oxidation,
Lanzhou Institute of Chemical Physics, Chinese Academy of Sciences,
Lanzhou, China and Graduate School of Chinese Academy of Sciences,
Beijing, China
Xiaoyin Wu
College of Earth and Environment Sciences, Lanzhou University,
Lanzhou, China
Yuru Kang and Liming Yang
State Key Laboratory for Oxo Synthesis and Selective Oxidation,
Lanzhou Institute of Chemical Physics, Chinese Academy of Sciences,
Lanzhou, China
Abstract: An efficient one-pot four-component coupling process for the synthesis of
polyhydroquinoline derivatives catalyzed by montmorillonite K10 clay is described.
This procedure has such advantages as short reaction time, high yields, and simple
workup. The catalyst could be reused several times and keeps its initial activity in
the recycle reactions.
Keywords: Montmorillonite K10, one-pot synthesis, polyhydroquinoline derivatives,
solid catalyst
Received in Japan April 28, 2005
Address correspondence to Liming Yang, State Key Laboratory for Oxo Synthesis
and Selective Oxidation, Lanzhou Institute of Chemical Physics, Chinese Academy of
Sciences, Lanzhou 730000, China. E-mail: limy@lzb.ac.cn
2
875

2
876
INTRODUCTION
Hantzsch 1,4-dihydropyridines (1,4-DHPs) are well known as Ca channel
G. Song et al.
2
þ
[1]
blockers,
compounds such as vasodilator, bronchodilator, antiatherosclerotic, antitumor,
and they are also a common feature of various bioactive
[2]
geroprotective, hepatoprotective and antidiabetic agents. Recently, mostly
1
,4-DHPs derivatives combining single rings have been reported.
In the past, many methods for synthesis of polyhydroquinoline derivatives
[3]
[4]
have been reported, such as conventional heating, refluxing in acetic acid,
[
5]
[6]
and microwave irradiation and ultrasound. Ionic liquids have also been
used to promote the reaction. Although most of these processes offer distinct
advantages, they suffer from certain drawbacks such as long reaction time, unsa-
tisfactory yields, and high cost. Therefore, the development of new, efficient
methods for preparation of polyhydroquinoline is desired. In recent years, clay
catalysts, particularly montmorillonite, have received considerable attention in
[
7]
chemical synthesis. They are inexpensive, noncorrosive, and recyclable.
Thus, the montmorillonite-catalyzed procedures have many advantages, such
as environmental compatibility and easy handling. As a commercial product,
montmorillonite K10 clay (mont. K10) has been widely studied and found to
[
8a]
be useful in many reactions, such as the synthesis of b-acetamido ketones,
[
8b]
[8c]
the synthesis of biomarkers,
8d]
Michael addition,
(2,5) intramolecular ene cyclization,
[8e] [8f]
Friedel–Crafts reaction, Diels–Alder reaction, and
[
so on. Herein, we report our preliminary results on the synthesis of polyhydro-
quinoline derivatives catalyzed by mont. K10, as shown in Scheme 1.
RESULTS AND DISCUSSION
Initially, 4-chlorobenzaldehyde was selected as a probe aldehyde to optimize
the reaction conditions, and the results are listed in Table 1. Obviously, the
temperature and the amount of catalyst had important effects on the
reaction. With 20 wt% of catalyst, the yields of 3-carbethoxy-1,4,5,6,7,
0
8-hexahydro-4-(4 -chlorophenyl)-2,7,7-trimethyl-5-oxoquinoline (2b) increased
from 73% to 95% as the temperature increased from 20 to 808C (Table 1,
entries 1–3). Similar changes in the yields with the catalyst amount at a
constant temperature was also observed. Therefore, it was reasonable to
Scheme 1.

Montmorillonite K10 Clay as Catalyst
2877
a
Table 1. Effect of temperature and amount of catalyst on the reaction
Amount of
catalyst (wt %)
Temp.
(8C)
Time
(min)
Yield
b
(%)
Entry
1
2
3
4
5
20
20
20
10
5
80
50
20
80
80
20
60
95
85
73
88
81
120
40
100
a
All reactions were conducted with 4-chlorobenzaldehyde (2mmol),
ethyl acetoacetate (2mmol), dimetone (2mmol), and ammonium
acetate (3mmol).
b
Isolated yields.
conclude that the best conditions were 20 wt% of mont. K10 at 808C, where
the maximum yield of 95% could be obtained within 20 min.
Encouraged by these results, other aromatic aldehydes have been reacted
with dimedone, ammonium acetate, and ethyl acetoacetate, and the results are
listed in Table 2. It was evident that several aromatic aldehydes could be
converted to the corresponding products in high yield over the mont. K10
catalyst. Various substituents on the aromatic ring did not detrimentally
affect the yields. Benzaldehyde and other aromatic aldehydes containing
electron-withdrawing groups (such as nitro group, halide) or electron-
donating groups (such as hydroxyl group, alkoxyl group) were employed
and reacted well to give the corresponding polyhydroquinoline in good to
excellent yields. In our system, many acid-labile substrates such as
4
-methoxybenzaldehyde, vanillin, and piperonal all worked well. When the
aliphatic aldehyde was performed, a moderate yield was obtained (Table 2,
entry 10), which demonstrated aromatic aldehyde is more suitable in this
system. As a substitute of ethyl acetoacetate, methyl acetoacetate was also
carried out in our system with satisfaction (Table 2, entry 11).
Because the present catalyst is a solid material, it could be easily recycled
after reaction by simple filtration. After further treatments including washing
and activation at 1208C, the recycled catalyst has been examined in the next
run. In the reaction of 4-chlorobenzaldehyde, dimedone, ethyl acetoacetate,
and ammonium acetate, the mont. K10 catalyst could be reused three times
without obvious activity loss (Table 2, entry 2).
CONCLUSION
In conclusion, an efficient cyclization reaction of various aromatic aldehydes
with dimedone, ethyl acetoacetate, and ammonium acetate using mont. K10 as
solid catalyst was developed with high yields. In addition, the procedure has
several advantages including short reaction time, high yields, and simple

2878
G. Song et al.
Table 2. Synthesis of polyhydroquinoline derivatives catalyzed by montmorillonite
K10 at 808C
Mp (8C)
a
Time Yield
(%)
Entry
1
Aldehyde
Product (min)
Obtained
Reported
[
6]
2a
2b
50
20
93 225–226
227–229
9
91)
5
[5,6]
2
3
4
b
247–248 246–247
(
2c
30
60
91 238–240
84 220–222
2d
[6]
5
2e
30
95 243–244
251–253
[
[
6]
6]
6
7
2f
40
60
91 258–260
97 237–239
260–261
242–244
2g
[
5b]
8
9
2h
2i
80
40
90 202–204 210–212
[6]
92 270–272
267–268
1
0
1
2j
100
30
34
c
1
2k
91 222–223
a
b
c
Isolated yields.
The catalyst has been reused three times.
The reaction was conducted with 4-chlorobenzaldehyde (2 mmol), methyl aceto-
acetate (2 mmol), dimetone (2 mmol), and ammonium acetate (3 mmol).

Montmorillonite K10 Clay as Catalyst
2879
workup. Moreover, as an ecofriendly catalyst, mont. K10 is inexpensive and
can be reused several times, which makes it a useful and attractive process
for synthesis of these compounds.
Typical Procedure
A mixture of 4-chlorobenzaldehyde (2 mmol, 0.281 g), dimedone (2 mmol,
0
0
.281 g), ethyl acetoacetate (2 mmol, 0.261 g), ammonium acetate (3 mmol,
.231 g), and montmorillonite K10 (20 wt%, 0.21 g) in ethanol (5 ml) was
stirred at 808C for 20 min. After the reaction completed, the solid catalyst
was filtered and washed with ethanol. This ethanol solution was then put
into a 100-ml beaker containing ca. 250-ml of water to obtain the product
with a yield of 95% (0.71 g) after filtration and drying.
Analytical Data for Selected Compounds
21 1
a: IR (KBr): 3288, 1698, 1610 cm . H NMR (300 MHz, CDCl ): 0.92
3
2
(
s, 3H, CH ), 1.05 (s, 3H, CH ), 1.12 (t, 3H, J ¼ 7.2 Hz, CH CH ), 2.19
2 3 1 2 2 3
3
3
2
3
(
m, 4H, 2CH ), 2.38 (s, 3H, CH ), 4.08 (q, J ¼ J ¼ 6.8 Hz, 2H, CH CH ),
5
for C H NO : C, 74.31; H, 7.42; N, 4.12; Found: C, 74.45; H, 7.51; N, 4.06.
.02 (s, 1H, CH), 6.0 (s, 1H, NH), 7.03–7.28 (m, 5H, ArH). Anal. calcd.
2
1
25
3
21 1
2
b: IR (KBr): 3298, 1703, 1600cm . H NMR (300MHz, CDCl ): 0.91
3
(
s, 3H, CH ), 1.05 (s, 3H, CH ), 1.10 (t, 3H, J ¼ 7.2 Hz, CH CH ), 2.16 (m, 4H,
3
3
2
3
2
CH), 5.88 (s, 1H, NH), 7.13–7.26 (m, 4H, ArH). Anal. calcd. for C H ClNO :
CH ), 2.40 (s, 3H, CH ), 4.08 (q, J ¼ J ¼ 6.8 Hz, 2H, CH CH ), 4.98 (s, 1H,
21 24 3
2
3
1
2
2
3
C, 67.46; H, 6.47; N, 3.74. Found: C, 67.30; H, 7.44; N, 3.80.
2
21 1
c: IR (KBr): 3460, 3196, 1682, 1605 cm . H NMR (300 MHz, CDCl3):
0
.94 (s, 3H, CH ), 1.08 (s, 3H, CH ), 1.12 (t, 3H, J ¼ 7.2 Hz, CH CH ), 2.20
3
3
2
3
(
m, 4H, 2CH ), 2.35 (s, 3H, CH ), 4.05 (q, J ¼ J ¼ 7.2 Hz, 2H, CH CH ),
2
3
1
2
2
3
4
ArH). Anal. calcd. for C H NO : C, 70.95; H, 7.09; N, 3.94. Found: C,
.98 (s, 1H, CH), 5.65 (s, 1H, OH), 6.0 (s, 1H, NH), 7.14–7.27 (m, 4H,
2
1
25
4
7
0.75; H, 7.12; N, 3.86.
d: IR (KBr): 3400, 3290, 1676, 1608 cm
CDCl ): 0.94 (s, 3H, CH ), 1.06 (s, 3H, CH ), 1.15 (t, 3H, J ¼ 7.2 Hz,
2
1
1
2
. H NMR (300 MHz,
3
3
3
CH CH ), 2.19 (m, 4H, 2CH ), 2.31 (s, 3H, CH ), 4.02
2
3
2
3
(
q, J ¼ J ¼ 6.8 Hz, 2H, CH CH ), 5.02 (s, 1H, CH), 5.73 (s, 1H, OH), 6.0
21 25 4
1
2
2
3
(
s, 1H, NH), 7.04–7.26 (m, 4H, ArH). Anal. calcd. for C H NO : C,
0.95; H, 7.09; N, 3.94. Found: C, 70.55; H, 7.22; N, 3.78.
7
21 1
e: IR (KBr): 3282, 1690, 1602 cm . H NMR (300 MHz, CDCl ): 0.91
3
2
(
s, 3H, CH ), 1.07 (s, 3H, CH ), 1.16 (t, 3H, J ¼ 7.2 Hz, CH CH ), 2.20
2 3 1 2 2 3
3
3
2
3
(
m, 4H, 2CH ), 2.32 (s, 3H, CH ), 3.99 (q, J ¼ J ¼ 6.8 Hz, 2H, CH CH ),
4
.98 (s, 1H, CH), 5.91 (s, 2H, OCH O), 6.01 (s, 1H, NH), 7.01–7.23
2
(m, 3H, ArH). Anal. calcd. for C H NO : C, 68.91; H, 6.57; N, 3.65.
22 25 5
Found: C, 69.03; H, 6.44; N, 3.58.

2880
G. Song et al.
REFERENCES
1
2
. (a) Godfraid, T.; Miller, R.; Wibo, M. Calcium antagonism and calcium entry
blockade. Pharmocol. Rev. 1986, 38, 321–416; (b) Mannhold, R.; Jablonka, B.;
Voigdt, W.; Schoenafinger, K.; Schravan, K. Calcium- and calmodulin-
antagonism of elnadipine derivatives: Comparative SAR. Eur. J. Med. Chem.
1992, 27, 229–235.
. (a) Bossert, F.; Meyer, H.; Wehinger, E. 4-Aryldihydropyridines, a new class of
highly active calcium antagonists. Angew. Chem., Int. Ed. Engl. 1981, 20,
762–769; (b) Nakayama, H.; Kasoaka, Y. Chemical identification of binding
sites for calcium channel antagonists. Heterocycles. 1996, 42, 901–909.
3
4
. Sainani, J. B.; Shah, A. C. Synthesis of 4-aryl-1,4,5,6,7,8-hexahydro-5-oxo-2,7,
7-trimethyl-quinoline-3-carboxylate and amides. Indian J. Chem., Sect. B. 1994,
33, 526–531.
. Sufirez, M.; Ochoa, E.; Verdecia, Y.; Verdecia, B.; Moran, L.; Martin, N.;
Quinteiro, M.; Seoane, C.; Soto, J. L.; Novoa, H.; Blaton, N.; Peters, O. M.
A joint experimental and theoretical structural study of novel substituted
2
,5-dioxo-l,2,3,4,5,6,7,8-octahydroquinolines. Tetrahedron. 1999, 55, 875–884.
. (a) Ahluwalia, V. K.; Goyal, B.; Das, U. One-pot synthesis of 5-oxo-1,4,5,6,7,
-hexahydroquinolines and pyrimido[4,5-b] quinolines using microwave
5
8
irradiation and ultrasound. J. Chem. Res., Synop. 1997, 226; (b) Tu, S. J.;
Zhou, J. F.; Deng, X.; Cai, P. J.; Wang, H.; Feng, J. C. One-step synthesis of
4-arylpolyhydroquinoline derivatives using microwave irradiation. Chin. J. Org.
Chem. 2001, 21, 313–316.
6
7
. Ji, S. J.; Jiang, Z. Q.; Lu, J.; Loh, T. P. Facile ionic liquids-promoted one-pot
synthesis of polyhydroquinoline derivatives under solvent-free conditions.
Synlett. 2004, 5, 831–835.
. (a) Vaccari, A. Preparation and catalytic properties of cationic and anionic clays.
Catal. Today. 1998, 41, 53–71; (b) Gil, A.; Gandia, L. M.; Vicente, M. A. Recent
advances in the synthesis and catalytic applications of pilled clays. Catal. Rev.—
Sci. Eng. 2002, 42, 145–212; (c) Varma, R. S. Clay and clay-supported reagents in
organic synthesis. Tetrahedron. 2002, 58, 1235–1255.
8
. (a) Bahulayan, D.; Das, S. K.; Iqbal, J. Montmorillonite K10 clay: An efficient
catalyst for the one-pot stereoselective synthesis of b-acetamido ketones. J. Org.
Chem. 2003, 68, 5735–5738; (b) Li, T. S.; Wang, J. X.; Zheng, X. J. Simple
synthesis of allobetulin, 28-oxyallobetulin and related biomarkers from betulin
and betulinic acid catalysed by solid acids. J. Chem. Soc., Perkin Trans. 1 1998,
3
957; (c) Ohmura, H.; Smyth, G. D.; Mikami, K. The first example of (2,5) ene
cyclization: Solid acid-catalyzed oxonium-ene reaction. J. Org. Chem. 1999, 64,
056–6059; (d) Poupaert, J. H.; Bukuru, J.; Gozzo, A. Clay (montmorillonite K10)
6
catalysis of the Michael addition of a,b-unsaturated carbonyl compounds to
indoles: The beneficial role of alcohols. Monatsh. Chem. 1999, 130, 929;
(
e) Sieskind, O.; Albrecht, P. Synthesis of alkylbenzenes by Friedel–Crafts
reactions catalysed by K10-montmorillonite. Tetrahedron Lett. 1993, 34, 1197;
f) Avalos, M.; Babiano, R.; Bravo, J. L.; Cintas, P.; Jimenez, J. L.;
(
Palacios, J. C. Clay-catalyzed solventless addition reactions of furan with
a,b-unsaturated carbonyl compounds. Tetrahedron Lett. 1998, 39, 9301.