An efficient one-pot synthesis of polyhydroquinolines at room temperature using HY-zeolite

Article abstract of DOI:10.1248/cpb.54.1044

An efficient one-pot synthesis of polyhydroquinolines by four-component coupling reactions of aldehydes, ethyl acetoacetate, dimedone and ammonium acetate in the presence of HY-zeolite at ambient temperature has been achieved. The conversions took shorter

Full text of DOI:10.1248/cpb.54.1044

1
044
Notes
Chem. Pharm. Bull. 54(7) 1044—1045 (2006)
Vol. 54, No. 7
An Efficient One-Pot Synthesis of Polyhydroquinolines at Room
1)
Temperature Using HY-Zeolite
Biswanath DAS,* Bommena RAVIKANTH, Ravirala RAMU, and Bommena VITTAL RAO
Organic Chemistry Division-I, Indian Institute of Chemical Technology; Hyderabad–500 007, India.
Received January 27, 2006; accepted March 31, 2006
An efficient one-pot synthesis of polyhydroquinolines by four-component coupling reactions of aldehydes,
ethyl acetoacetate, dimedone and ammonium acetate in the presence of HY-zeolite at ambient temperature has
been achieved. The conversions took shorter times to form the products in excellent yields. HY-zeolite can be re-
covered and reused.
Key words polyhydroquinoline; four-component coupling; one-pot conversion; HY-zeolite; heterogeneous catalyst
In recent years heterogeneous catalysts have attracted a donating as well as electron withdrawing groups worked
great attention due to efficiency, economic and environmen- well. The aryl moiety having different groups or the same
tal considerations. HY-zeolite is an important heterogeneous group at different positions did not show much differences in
catalyst used in various chemical transformations, such as the yields of the products. Heterocyclic aldehyde like furfural
2)
liquid phase acylation of amines, direct conversion of alde- also underwent the facile transformation. The polyhydro-
3)
hydes into nitriles and ketones into amides, selective re- quinoline derivatives were formed within 2.0—2.5 h at room
4)
moval of N-Boc protecting group from aromatic amines and temperature in excellent yields (87—93%). In absence of the
5)
one-pot synthesis of 2,3-dihydro-2,2-dimethylbenzofurans.
catalyst no product could be detected within 3 h at room tem-
Thus the remarkable catalytic activity together with easy perature under the present experimental conditions. The pres-
availability, operational simplicity and recoverability of HY- ent catalyst can conveniently be handled and removed from
zeolite encouraged us to utilize this catalyst for the synthesis the reaction mixture. Moreover, it can be recovered and
of polyhydroquinolines having 1,4-dihydropyridine moiety.
,4-Dihydropyridines exhibit a variety of biological prop-
reused for at least three times without loss of its activity.
In conclusion, we have developed a convenient and effi-
1
erties. They can cure the disordered heart ratio as a chain- cient protocol for one-pot synthesis of polyhydroquinolines
cutting agent of factor IV channel and also possess the cal- by four-component coupling reactions of aldehydes, ethyl
6—8)
cium channel agonist-antagonist modulation activities.
acetoacetate, dimedone and ammonium acetate in the pres-
These compounds also behave as neuroprotectants, cerebral ence of HY-zeolite as a catalyst. The method is associated
9,10)
antiischaemic agents and chemosensitizers.
with several advantages such as simple experimental proce-
1,4-Dihydropyridines were synthesized more than a cen- dure (column chromatography), utilization of a heteroge-
tury ago by Hantzsch by heating a mixture of an aldehyde, a neous catalyst, milder conditions, short reaction times, excel-
b-ketoester and ammonia in ethanol under reflux for several lent yields and reusability of the catalyst. We feel the method
11)
hours. Different other heating approaches for the syntheses will find important applications for the synthesis of polyhy-
of polyhydroquinoline derivatives have subsequently been re- droquinolines.
1
2—16)
ported.
However, these methods require drastic reaction
Experimental
conditions and long reaction times. Recently microwave irra-
diation has also been applied for the preparation of polyhy-
To a mixture of an aldehyde (1 mmol), ethyl acetoacetate (1 mmol), dime-
done (1 mmol) and NH OAc (1.5 mmol) in CH CN (10 ml) was added HY-
4
3
17)
18)
19)
droquinolines. Yb(OTf)3 or iodine have been found to zeolite (100 mg) (PQ Corporation, U.S.A.). The mixture was stirred at room
catalyze the Hantzsch reaction at ambient temperature but temperature and the reaction was monitored by TLC. After completion, the
mixture was filtered and the catalyst was recovered from the residue by
washing with EtOAc (3ꢀ10 ml) and was subsequently activated by heating
at 80 °C for 12 h for recyclization. CH CN was removed from the above fil-
trate and water (10 ml) was added. The mixture was extracted with EtOAc
using the first catalyst the times required for the conversions
were 2—8 h while using the second catalyst at room temper-
ature the time of conversions was 1.5—6 h. The second cata-
3
lyst should also properly be removed from the reaction mix- (3ꢀ10 ml) and the extract was concentrated. The solid mass was subjected
ture during work-up.
In continuation of our work
heterogeneous catalysts on organic transformations we report
here a convenient and efficient method for the synthesis of
to column chromatography over silica gel using 30% EtOAc in hexane as
eluent to obtain pure polyhydroquinone derivative. The structures of all the
2
0—24)
on the applications of
1
2,16,18,25)
products (which are known compounds)
spectral (IR, H-NMR and MS) data.
were established from their
1
The recovered HY-zeolite was utilized consecutively three times for the
polyhydroquinolines (containing 1,4-dihydropyridine moi- reaction of benzaldehyde, ethyl acetoacetate, dimedone and ammonium ac-
ety) using HY-zeolite as a catalyst. Four-component coupling etate (Table 1, entry 1) following the above procedure to produce the corre-
sponding polyhydroquinoline with the yields of 90, 89 and 87%.
reactions of aldehydes, ethyl acetoacetate, dimedone and am-
monium acetate were carried out using this catalyst at room
temperature (Chart 1).
A series of polyhydroquinoline derivatives were prepared
following the above method using various aldehydes (Table
1). Both aromatic and aliphatic aldehydes underwent the con-
version smoothly. Aromatic aldehydes containing electron
Chart 1
∗
To whom correspondence should be addressed. e-mail: biswanathdas@yahoo.com
© 2006 Pharmaceutical Society of Japan

July 2006
1045
Table 1. Synthesis of Polyhydroquinolines at Room Temperature Using
HY-Zeolite
Acknowledgement The authors thank CSIR and UGC, New Delhi for
financial assistance.
a)
Time
h)
Yield
(%)
References and Notes
1) Part 70 in the series “Studies on novel synthetic methodologies.”
Entry
1
Aldehyde
Product
Ref.
16
b)
(
2)
3)
4)
5)
6)
7)
8)
Narender N., Srinivasu P., Kulkarni J. S., Raghavan K. V., Green
Chem., 2000, 104—105 (2000).
Srinivas K. V. N. S., Reddy E. B., Das B., Synlett, 2002, 625—627
(2002).
2.0
2.0
93
90
Ravindranath N., Ramesh C., Reddy M. R., Das B., Adv. Synth. Catal.,
3
45, 1207—1208 (2003).
Kim H. J., Seo G., Kim J.-N., Choi K. H., Bull. Korean Chem. Soc.,
5, 1726—1728 (2004).
2
Kawase M., Shah A., Gaveriya H., Motohashi N., Sakagami H., Varga
A., Molnar J., Bioorg. Med. Chem., 10, 1051—1055 (2002).
Shan R., Velazquez C., Knaus E. E., J. Med. Chem., 47, 254—261
2
3
4
5
16
18
16
16
(2004).
Sawada Y., Kayakiri H., Abe Y., Mizutani T., Inamura N., Asano M.,
Hatori C., Aramori I., Oku T., Tanaka H., J. Med. Chem., 47, 2853—
2
863 (2004).
2.25
2.25
2.5
92
90
88
9)
Klusa V., Drugs Future, 20, 135—138 (1995).
1
1
1
0) Boer R., Gekeler V., Drugs Future, 20, 499—509 (1995).
1) Hantzsch A., Ann. Chem., 215, 1—82 (1882).
2) Sainani J. B., Shah A. C., Arya V. P., Indian J. Chem., 33B, 526—531
(1994).
1
1
3) Ahluwalia V. K., Goyal B., Indian J. Chem., 35B, 1021—1025 (1996).
4) Ahluwalia V. K., Goyal B., Das U., J. Chem. Res. (S), 1997, 266
(1997).
1
5) Margarita S., Estael O., Yamila V., Beatriz P., Lourdes M., Nazario M.,
Margarita Q., Carlos S., Jose L. S., Hector N., Norbert B., Oswald M.
P., Tetrahedron, 55, 875—884 (1999).
1
1
6) Ji S.-J., Jiang Z.-Q., Lu J., Loh T.-P., Synlett, 2004, 831—835 (2004).
7) Tu S.-J., Zhou J.-F., Deng X., Cai P.-J., Wang H., Feng J.-C., Chin. J.
Org. Chem., 21, 313 (2001).
1
1
2
2
8) Wang L.-M., Sheng J., Zhang L., Han J.-W., Fan Z.-Y., Tian H., Qian
C.-T., Tetrahedron, 61, 1539—1543 (2005).
9) Ko S., Sastry M. N. V., Lin C., Yao C.-F., Tetrahedron Lett., 46,
5771—5774 (2005).
6
7
2.5
87
90
12
16
0) Das B., Mahender G., Kumar V. S., Chowdhury N., Tetrahedron Lett.,
4
5, 6709—6711 (2004).
1) Das B., Reddy V. S., Reddy M. R., Tetrahedron Lett., 45, 6717—6719
2004).
22) Srinivas K. V. N. S., Das B., Synlett, 2004, 1715—1718 (2004).
(
2.25
23) Das B., Benerjee J., Chem. Lett., 33, 960—961 (2004).
24) Das B., Benerjee J., Ravindranath N., Tetrahedron, 60, 8357—8361
(2004).
25) Ono M., Wada Y., Sun L., Chen S., Przewloka T., Zhang S., Borella
C., Koya K., Foley K., Xia Z.-Q., Li H., Zhou D., PCT Int. App., WO,
8
9
2.5
2.0
92
90
16
16
2
5, 507 (2005).
1
1
0
1
2.5
2.5
88
90
25
18
1
2
2.25
90
18
1
a) The structures of the products were established from their spectral (IR, H-NMR
and MS) data. b) Yields are given for isolated products.