An efficient one-pot synthesis of pyrano- and furoquinolines employing two reusable solid acids as heterogeneous catalysts

Article abstract of DOI:10.1055/s-2004-829576

Two solid acids, Fe³⁺-K-10 montmorillonite clay and HY-zeolite have been employed efficiently for single-step synthesis of pyrano- or furoquinolines in high yields and high diastereoselectivities by coupling of three components: anilines, benzaldehydes and 3,4-dihydro-2h-pyran or 2,3-dihydrofuran. Both the heterogeneous catalysts are recoverable and recyclable.

Full text of DOI:10.1055/s-2004-829576

LETTER
1715
An Efficient One-Pot Synthesis of Pyrano- and Furoquinolines Employing
Two Reusable Solid Acids as Heterogeneous Catalysts1
An
E
fficient One-P
.
ot Synthesis
V
of Pyrano
a
nd Fu
.
roquinolinesN. S. Srinivas, Biswanath Das*
Organic Chemistry Division-I, Indian Institute of Chemical Technology, Hyderabad-500 007, India.
Fax +91(40)27160512; E-mail: biswanathdas@yahoo.com
Received 30 March 2004
coupling are known.4,5 However, many of the imines are
hygroscopic, unstable and difficult to purify and so the
process involving the preparation and purification of these
imines separately, and subsequent utilization of them for
Abstract: Two solid acids, Fe3+-K-10 montmorillonite clay and
HY-zeolite have been employed efficiently for single-step synthesis
of pyrano- or furoquinolines in high yields and high diastereoselec-
tivities by coupling of three components: anilines, benzaldehydes
and 3,4-dihydro-2H-pyran or 2,3-dihydrofuran. Both the heteroge- coupling with enol ethers, are not advantageous. The
neous catalysts are recoverable and recyclable.
Lewis acid GdCl3, which was used earlier for one-pot
preparation of pyranoquinoline derivatives, was also not
shown to be reusable.5 Thus there is a need to develop ef-
ficient and economic processes for single step synthesis of
pyranoquinolines and related compounds.
Key words: Pyrano- and furoquinolines, solid acids, multicompo-
nent coupling, diastereoselectivity
Pyranoquinoline derivatives are known to possess various
important biological properties such as antiallergic, anti-
inflammatory and estrogenic activities.2 Several bioactive
alkaloids contain a pyranoquinoline moiety.3 Generally
the pyranoquinolines are prepared by aza-Diels–Alder re-
actions of imines (derived from aromatic amines) with
3,4-dihydro-2H-pyran. Different Lewis acids are known
to catalyze such reactions.4 However, many of these
Lewis acids are not easily available or expensive, non-re-
usable and afford the mixture of products with unsatisfac-
tory yields. More importantly, several Lewis acids cannot
be utilized for single-step coupling of aldehydes, amines
and enol ethers because they will be decomposed or deac-
tivated by amines and water formed in the intermediate
imine formation step. This may be a reason for the limited
number of reported methods for one-pot coupling of these
three components, though various methods for multistep
In connection with our work on the development of novel
synthetic methodologies utilizing the solid acids such as
Fe3+-K-10 montmorillonite clay6a and HY-zeolite6b we
have recently observed that these two catalysts can effi-
ciently be employed for one-pot synthesis of pyrano- and
furoquinolines by coupling of the three components,
anilines (1), benzaldehydes (2) and 3,4-dihydro-2H-pyran
or 2,3-dihydrofuran (3) (Scheme 1).
Different anilines and benzaldehydes were treated with
3,4-dihydro-2H-pyran or 2,3-dihydrofuran to produce a
series of pyrano or furoquinolines (Table 1). Fe3+-K-10
clay catalyzed the reaction at room temperature while
HY-zeolite under reflux.7 The times required for the first
catalyst to complete the conversion were shorter (3–4 h)
than those required for the second catalyst (5–6 h). The
products (4 and 5) were obtained in high yield and high
diastereoselectivities. These were the mixture of trans-
O
R2
( )n
Fe3+-K-10 clay
CHO
NH2
R1
CH3CN
r.t., 3–4 h
R3
( )n
N
H
+
+
or
R1
O
R4
R3
HY-zeolite
4 (trans)
CH2Cl2
reflux, 5–6 h
R4
R2
+
3
2
1
O
n = 1, 2
R2
( )n
R3
R4
N
H
R1
5 (cis)
Scheme 1
SYNLETT 2004, No. 10, pp 1715–1718
0
9
.0
8
.2
0
0
4
Advanced online publication: 15.07.2004
DOI: 10.1055/s-2004-829576; Art ID: D08104ST
© Georg Thieme Verlag Stuttgart · New York

1716
K. V. N. S. Srinivas, B. Das
LETTER
and cis-isomers that could be separated by column vinyl ethers in the presence of Fe3+-K-10 clay was
chromatography over silica gel. The trans-isomer (4) was reported4c to form two products, one formed by [4+2] ad-
the major and cis-isomer (5) minor in each conversion. dition and the other by [2+2] addition. Here we could not
The ratio of the isomers produced in a reaction was deter- get any product derived by [2+2] addition of 3,4-dihydro-
mined by 1H NMR spectrum of the crude product and the 2H-pyran or 2,3-dihydrofuran with the intermediate imi-
structures of the products were established from the spec- nes.
tral (1H NMR and MS) data of the pure compounds.7 Pre-
viously the cycloaddition of N-benzylidiene aniline with
Table 1 Preparation of Pyrano- and Furoquinolines Using Solid Acids Fe3+-K-10 Clay and HY-Zeolitea
Entry Aniline (1)
Benzaldehyde (2)
Olefin (3)
Catalystb
Time (h)
Isolated yield (%) Product ratioc (4:5)
R1
R2
H
R3
H
R4
H
n
2
a
b
c
d
e
f
H
H
H
H
H
H
H
H
H
Me
H
H
H
H
H
i
3.5
5.0
4.0
5.5
3.0
5.0
4.0
5.5
3.0
5.0
3.5
5.5
3.5
5.0
4.0
6.0
4.0
5.5
4.0
6.0
3.5
5.5
4.0
5.5
3.0
5.0
3.0
5.5
3.5
86
82
90
85
91
86
89
83
92
88
86
84
89
81
88
83
85
81
76
73
84
79
91
83
85
82
88
86
87
84:16
87:13
91:09
88:12
92:08
89:11
85:15
84:16
90:10
87:13
85:15
86:14
90:10
87:12
83:17
79:21
80:20
78:22
74:26
77:23
82:18
84:16
89:11
83:17
84:16
87:13
89:11
85:15
88:12
ii
i
H
H
OMe
Cl
2
2
2
2
2
2
2
2
2
1
1
1
1
1
ii
i
H
H
ii
i
H
OCH2O
ii
i
H
Cl
H
H
H
H
H
H
H
H
Cl
H
Cl
H
ii
i
Cl
Me
Me
OMe
H
ii
i
g
h
i
H
ii
i
Cl
H
ii
i
ii
i
j
H
ii
i
k
l
H
H
ii
i
H
OMe
Cl
Cl
H
ii
i
m
n
o
H
ii
i
H
ii
i
Me
Synlett 2004, No. 10, 1715–1718 © Thieme Stuttgart · New York

LETTER
An Efficient One-Pot Synthesis of Pyrano and Furoquinolines
1717
Table 1 Preparation of Pyrano- and Furoquinolines Using Solid Acids Fe3+-K-10 Clay and HY-Zeolitea (continued)
Entry Aniline (1)
Benzaldehyde (2)
Olefin (3)
Catalystb
ii
Time (h)
5.5
Isolated yield (%) Product ratioc (4:5)
R1
R2
R3
H
H
H
R4
Cl
H
n
82
92:08
p
q
r
H
Me
OMe
H
1
1
1
i
4.0
6.0
4.0
5.5
4.0
6.0
84
78
81
77
74
71
80:20
83:17
78:22
79:21
76:24
75:25
ii
i
H
ii
i
Me
H
ii
a All the products were characterized from their spectral (1H NMR and MS) data.
b Catalyst: (i) Fe3+-K-10 clay, (ii) HY-zeolite.
c Product ratio was determined from the 1H NMR spectrum of the crude product.
In the present protocol the imines generated in situ by con- References
densation of anilines and benzaldehydes act as hetero-
(1) Part 41 in the series ‘Studies on Novel Synthetic
Methodologies’.
dienes, which undergo aza-Diels–Alder reaction with 3,4-
dihydro-2H-pyran or 2,3-dihydrofuran in the presence of
Fe3+-K-10 clay or HY-zeolite to form the corresponding
pyrano- or furoquinolines. The synthesis could not be
achieved in absence of any of these catalysts.
(2) (a) Faber, K.; Stueckler, H.; Kappe, T. J. Heterocycl. Chem.
1984, 21, 1171. (b) Johnson, J. V.; Rauckman, S.;
Beccanari, P. D.; Roth, B. J. Med. Chem. 1989, 32, 1942.
(c) Yamada, N.; Kadowaki, S.; Takahashi, K.; Umeza, K.
Biochem. Pharmacol. 1992, 44, 1211.
The catalysts, Fe3+-K-10 montmorillonite clay and HY-
zeolite work under heterogeneous conditions. In recent
years, heterogeneous catalysts are gaining more impor-
tance due to environmental and economic considerations.
The first catalyst can easily be prepared8 from the readily
available and inexpensive FeCl3 and K-10 montmorillo-
nite clay while the second catalyst is commercially avail-
able.7 Both, the catalysts can safely be handled. They can
be recovered and reused for at least three times without
loosing their activity.
(3) Ramesh, M.; Mohan, P. S.; Shanmugam, P. Tetrahedron
1984, 40, 4041.
(4) (a) Boger, D. L.; Weinreb, S. M. Hetero-Diels–Alder
Methodology in Organic Synthesis; Academic Press: San
Diego, 1987, Chap. 2 and 9. (b) Boger, D. L.; Weinreb, S.
M. Hetero-Diels–Alder Methodology in Organic Synthesis;
Academic Press: San Diego, 1987, Chap. 9. (c) Cabral, J.;
Laszlo, P.; Montaufier, M. T. Tetrahedron Lett. 1988, 29,
547. (d) Weinreb, S. M. In Comprehensive Organic
Synthesis, Vol. 5; Trost, B. M.; Fleming, I., Eds.; Pergamon:
Oxford, 1991, 401–449. (e) Babu, G.; Perumal, P. T.
Tetrahedron Lett. 1998, 39, 3225. (f) Yadav, J. S.; Reddy,
B. V. S.; Srinivas, R.; Madhuri, Ch.; Ramalingam, T. Synlett
2001, 240.
(5) Ma, Y.; Qian, C.; Xie, M.; Sun, J. J. Org. Chem. 1999, 64,
6462.
(6) (a) Srinivas, K. V. N. S.; Das, B. J. Org. Chem. 2003, 68,
1165. (b) Srinivas, K. V. N. S.; Reddy, E. B.; Das, B. Synlett
2002, 625.
(7) General Procedure for the Preparation of Pyrano- and
Furoquinolines: To a solution of aniline (1 mmol),
benzaldehyde (1 mmol) and 3,4-dihydro-2H-Pyran or 2,3-
dihydrofuran (0.1 mL) in MeCN or CH2Cl2 (10 mL) Fe3+-K-
10 clay or HY-zeolite (PQ Corporation, USA; 100 mg) was
added. The mixture was stirred at r.t. with the first catalyst
but refluxed with the second catalyst under N2 atmosphere.
The reaction was monitored by TLC. After completion of the
reaction, the mixture was filtered. The concentrated filtrate
was subjected to column chromatography over silica gel and
the column was eluted with hexane–EtOAc (20:1) to afford
the pyrano- or furoquinolines. Both the catalyst, Fe3+-K-10
clay and HY-zeolite were recovered by washing the residue
of filtration with MeCN and CH2Cl2, respectively, activated
and recycled.
In conclusion, we have developed a very simple and effi-
cient method for one-step synthesis of pyrano- and furo-
quinolines by coupling of the three components, anilines,
benzaldehydes and dihydropyran or furan catalyzed by
two recyclable solid acids, Fe3+-K-10 clay and HY-zeo-
lite. The quinoline derivatives were formed in high yields
and high diastereoselectivities. The method is associated
with the benefits derived from both multicomponent cou-
pling and the utilization of heterocyclic recyclable cata-
lysts. We feel the present protocol will find important
applications for the synthesis of pyrano- and furoquino-
lines.
Acknowledgment
The authors thank CSIR, New Delhi and IICT for financial
assistance.
All the prepared compounds are known. The spectral data of
some representative pyrano and furoquinolines are given
below.
Synlett 2004, No. 10, 1715–1718 © Thieme Stuttgart · New York

1718
K. V. N. S. Srinivas, B. Das
LETTER
4b: solid, mp 146–147 °C. 1H NMR (200 MHz, CDCl3): d =
7.32 (2 H, d, J = 8.0 Hz), 7.18 (1 H, d, J = 8.0 Hz), 7.04 (1
H, t, J = 8.0 Hz), 6.84 (2 H, d, J = 8.0 Hz), 6.64 (1 H, t,
J = 8.0 Hz), 6.45 (1 H, d, J = 8.0 Hz), 4.64 (1 H, d, J = 10.0
Hz), 4.36 (1 H, d, J = 2.5 Hz), 4.06 (1 H, m), 3.97 (1 H, d,
J = 3.0 Hz), 3.82 (3 H, s), 3.63 (1 H, t, J = 10.0 Hz), 2.02 (1
H, m), 1.82 (1 H, m), 1.64 (1 H, m), 1.44 (1 H, m), 1.28 (1
H, m). MS–FAB: m/z = 296 [M+ + 1].
(1 H, m), 3.40 (1 H, m), 2.08 (1 H, m), 1.57–1.32 (4 H, m).
MS–FAB: m/z = 300 [M+ + 1].
4d: solid, mp 152–153 °C. 1H NMR (200 MHz, CDCl3): d =
7.18 (1 H, d, J = 8.0 Hz), 7.04 (1 H, t, J = 8.0 Hz), 6.92 (1 H,
d, J = 2.5 Hz), 6.84–6.62 (3 H, m), 6.46 (1 H, d, J = 8.0 Hz),
5.96 (2 H, s), 4.62 (1 H, d, J = 10.0 Hz), 4.36 (1 H, d, J = 3.5
Hz), 4.10 (1 H, m), 3.98 (1 H, br s), 3.70 (1 H, m), 2.02 (1 H,
m), 1.85–1.22 (4 H, m). MS–FAB: m/z = 310 [M+ + 1].
5d: solid, mp 160–161 °C. 1H NMR (200 MHz, CDCl3): d =
7.38 (1 H, d, J = 8.0 Hz), 7.04 (1 H, t, J = 8.0 Hz), 6.92–6.76
(4 H, m), 6.56 (1 H, d, J = 8.0 Hz), 5.96 (2 H, s), 5.24 (1 H,
d, J = 6.0 Hz), 4.60 (1 H, d, J = 3.0 Hz), 3.78 (1 H, br s),
3.60–3.38 (2 H, m), 2.05 (1 H, m), 1.60–1.38 (4 H, m). MS–
FAB: m/z = 310 [M+ + 1].
5b: solid, mp 154–155 °C. 1H NMR (200 MHz, CDCl3): d =
7.38 (1 H, d, J = 8.0 Hz), 7.30 (2 H, d, J = 8.0 Hz), 7.00 (1
H, m), 6.82 (2 H, d, J = 8.0 Hz), 6.77 (1 H, t, J = 8.0 Hz),
6.50 (1 H, d, J = 8.0 Hz), 5.26 (1 H, d, J = 3.0 Hz), 4.60 (1
H, d, J = 3.0 Hz), 3.84 (1 H, m), 3.82 (3 H, s), 3.58 (1 H, m),
3.22 (1 H, m), 2.04 (1 H, m), 1.58–1.30 (4 H, m). MS–FAB:
m/z = 296 [M+ + 1].
4m: solid, mp 147–148 °C. 1H NMR (200 MHz, CDCl3):
d = 7.35 (4 H, s), 7.14 (1 H, d, J = 8.0 Hz), 7.05 (1 H, t,
J = 8.0 Hz), 6.64 (1 H, d, J = 8.0 Hz), 6.42 (1 H, d, J = 8.0
Hz), 4.58 (1 H, d, J = 5.0 Hz), 4.08 (1 H, m), 3.85–3.42 (3 H,
m), 2.45 (1 H, m), 2.00 (1 H, m), 1.72 (1 H, m). MS–FAB:
m/z = 286 [M+ + 1].
4c: semi-solid. 1H NMR (200 MHz, CDCl3): d = 7.32 (4 H,
s), 7.16 (1 H, d, J = 8.0 Hz), 7.04 (1 H, t, J = 8.0 Hz), 6.68 (1
H, t, J = 8.0 Hz), 6.48 (1 H, d, J = 8.0 Hz), 4.67 (1 H, d,
J = 10.0 Hz), 4.92 (1 H, d, J = 2.5 Hz), 4.05 (1 H, m), 3.95
(1 H, br s), 3.68 (1 H, t, J = 10.0 Hz), 2.01 (1 H, m), 1.80 (1
H, m), 1.63 (1 H, m), 1.44 (1 H, m), 1.22 (1 H, m). MS–FAB:
m/z = 300 [M+ + 1].
5m: solid, mp 152–153 °C. 1H NMR (200 MHz, CDCl3):
d = 7.40 (1 H, d, J = 8.0 Hz), 7.36 (4 H, s), 7.05 (1 H, t,
J = 8.0 Hz), 6.68 (1 H, t, J = 8.0 Hz), 5.25 (1 H, d, J = 8.0
Hz), 4.65 (1 H, d, J = 3.0 Hz), 3.78 (1 H, br s), 3.62–3.40 (2
H, m), 2.18 (1 H, m), 1.62–1.50 (2 H, m). MS–FAB: m/z =
286 [M+ + 1].
5c: viscous. 1H NMR (200 MHz, CDCl3): d = 7.38 (1 H, d,
J = 8.0 Hz), 7.35 (4 H, s), 7.02 (1 H, t, J = 8.0 Hz), 6.74 (1
H, d, J = 8.0 Hz), 6.53 (1 H, d, J = 8.0 Hz), 5.24 (1 H, d,
J = 8.0 Hz), 4.65 (1 H, d, J = 2.5 Hz), 3.72 (1 H, m), 3.55
(8) Laszlo, P.; Mathy, A. Helv. Chim. Acta 1987, 70, 557.
Synlett 2004, No. 10, 1715–1718 © Thieme Stuttgart · New York