Tungstophosphoric acid-catalyzed imino-diels-alder reaction: An efficient one-pot synthesis of pyrano-and furanoquinoline derivatives

Article abstract of DOI:10.1080/00397910902838946

Tungstophosphoric acid has been found to be an efficient catalyst for the synthesis of pyranos-and furanoquinolines through the Imino-Diels-Alder reaction involving one-pot coupling of benzaldehydes, anilines, and 3,4-dihydro-2H-pyran or 2,3-dihydrofuran.

Full text of DOI:10.1080/00397910902838946

This article was downloaded by: [Duke University Libraries]
On: 19 January 2013, At: 15:25
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
Tungstophosphoric
Acid–Catalyzed Imino-
Diels–Alder Reaction: An
Efficient One-Pot Synthesis of
Pyrano- and Furanoquinoline
Derivatives
a
a
Biswanath Das , P. Balasubramanyam
,
a
Maddeboina Krishnaiah & Boyapati Veeranjaneyulu
a
a
Organic Chemistry Division I, Indian Institute of
Chemical Technology, Hyderabad, Andhra Pradesh,
India
Version of record first published: 07 Oct 2009.
To cite this article: Biswanath Das , P. Balasubramanyam , Maddeboina Krishnaiah &
Boyapati Veeranjaneyulu (2009): Tungstophosphoric Acid–Catalyzed Imino-Diels–Alder
Reaction: An Efficient One-Pot Synthesis of Pyrano- and Furanoquinoline Derivatives,
Synthetic Communications: An International Journal for Rapid Communication of
Synthetic Organic Chemistry, 39:21, 3825-3832
To link to this article: http://dx.doi.org/10.1080/00397910902838946
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.

1
Synthetic Communications , 39: 3825–3832, 2009
Copyright # Taylor & Francis Group, LLC
ISSN: 0039-7911 print=1532-2432 online
DOI: 10.1080/00397910902838946
Tungstophosphoric Acid–Catalyzed
Imino-Diels–Alder Reaction: An Efficient
One-Pot Synthesis of Pyrano- and
Furanoquinoline Derivatives
Biswanath Das, P. Balasubramanyam,
Maddeboina Krishnaiah, and Boyapati Veeranjaneyulu
Organic Chemistry Division I, Indian Institute of Chemical Technology,
Hyderabad, Andhra Pradesh, India
Abstract: Tungstophosphoric acid has been found to be an efficient catalyst for
the synthesis of pyranos- and furanoquinolines through the Imino-Diels–Alder
reaction involving one-pot coupling of benzaldehydes, anilines, and 3,4-dihydro-
2 H-pyran or 2,3-dihydrofuran. The products are formed at room temperature in
excellent yields in a short period of time.
Keywords: Imino-Diels–Alder reaction, pyrano- and furanoquinolines,
tungstophosphoric acid
INTRODUCTION
Pyrano- and furanoquinolines have attracted much attention because of
their broad spectra of biological properties
[1–4]
and occurrence in several
[5]
[6–12]
bioactive natural alkaloids. These compounds are generally prepared
by aza-Diels–Alder reaction of imines (derived from aldehydes and amines)
with 3,4-dihydro-2H-pyran or 2,3-dihydrofuran employing Lewis acids as
catalysts. However, the use of expensive catalysts, formation of mixtures of
Received December 1, 2008.
Part 176 in the series ‘‘Studies on novel synthetic methodologies.’’
Address correspondence to Biswanath Das, Organic Chemistry Division I,
Indian Institute of Chemical Technology, Uppal Road, Hyderabad 500 007,
Andhra Pradesh, India. E-mail: biswanathdas@yahoo.com
3
825

3826
B. Das et al.
products, unsatisfactory yields, and long reaction times are the drawbacks
in several of these methods. Many of the imines are also hygroscopic,
unstable, and difficult to purify, and thus the preparation of these com-
pounds separately is not advantageous. Another problem is that several
Lewis acids cannot be employed for one-pot coupling of aldehydes,
amines, and enol ethers because they will be decomposed or deactivated
by the amines and water formed in the intermediate imine-formation step.
Thus, few methods for single-step coupling of these three components have
been developed. Here we report the catalytic activity of a heteropoly acid
for such a reaction for the preparation of pyrano- and furanoquinolines.
RESULTS AND DISCUSSION
[13–15]
In continuation of our work on the discovery of useful and
improved synthetic methodologies, we have observed that the one-pot
coupling of benzaldehydes 1, anilines 2, and 3,4-dihydro-2H-pyran or
2
,3-dihydrofuran 3 can efficiently be carried out using tungstophosphoric
acid (TPA) as a catalyst (Scheme 1).
Initially the conversion was conducted with benzaldehyde, aniline,
and 3,4-dihydro-2H-pyran in the presence of different amounts of TPA
in MeCN at room temperature (Table 1). Considering the yields and
reaction times, 5 mol% of the catalyst was considered to be suitable to
carry out the reaction. Different solvents such as MeCN, tetrahydrofuran
(THF), CH Cl , and toluene were utilized for this reaction, but MeCN
2 2
was preferred because the yield of the corresponding quinoline was
greatest.
A series of pyrano- and furanoquinolines were prepared from various
benzaldehydes and anilines (Table 2). The conversion was complete
within 30–50 min, and the quinoline derivatives were formed in excellent
yields. The products were the mixtures of trans- and cis- isomers, which
were separated by column chromatograph over silica gel. The trans-
isomer 4 was the major isomer, whereas the cis-isomer 5 was the minor
1
one in each case. The ratio of these two isomers was determined by H
Scheme 1. Synthesis of pyrano- and furanoquinolines using TPA.

Pyrano- and Furanoquinoline Derivatives
3827
a
Table 1. Optimization of catalyst loading
Catalyst
loading (mol%)
Time
(min)
Isolated
yield (%)
Entry
a
b
c
d
e
f
1
5
10
15
20
0
40
40
40
40
40
180
55
92
93
93
94
0
a
The reaction of benzaldehyde, aniline, and 3,4-dyhydro-
H-pyran was conducted using different amounts of PTA
2
in MeCN at room temperature.
NMR spectra of the crude products, and their structures were established
1
from the spectral ( H NMR and MS) and analytical data of the pure com-
pounds. The four isomeric products (two sets of trans- and cis- isomers)
from the reaction of benzaldehyde, m-methyl aniline, and 3,4-dihydro-
2
H-pyran (Scheme 2) were successfully isolated and characterized.
Table 2. Synthesis of pyrano- and furanoquinolines using TPA
Benzaldehyde (1) Aniline (2)
Olefin Time Isolated Product
(3) (min) yield (%) ratio (4:5)
1
2
3
4
5
R
a
Entry
R
R
R
R
a
b
c
d
e
f
g
h
i
j
k
l
m
n
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
Cl
F
2
2
2
2
2
2
2
2
1
1
1
1
1
1
30
40
45
40
40
50
40
40
30
45
40
50
45
45
92
91
89
87
93
86
94
89
90
89
88
86
90
88
62:38
61:39
63:37
60:40
62:38
59:41
60:40
61:39
59:41
62:38
61:39
59:41
63:37
64:36
H
OMe H
H
H
H
Me
H
Ome
H
H
H
H
H
H
H
Me
H
H
H
Cl
F
Cl
Ome
H
H
H
H
H
Cl
H
H
H
H
H
H
H
H
H
H
H OMe
H Me
a
1
The ratio of 4 and 5 was determined by H NMR spectra of the crude
1
products, and their structures were determined from the spectra ( H NMR and
MS) and analytical data of the pure compounds.

3828
B. Das et al.
Scheme 2. Synthesis of pyranoquinolines using TPA.
The conversion can be explained by in situ formation of imines (by
condensation of benzaldehydes and anilines), which act as heterodienes
to undergo aza-Diels–Alder reactions with 3,4-dihydro-2H-pyran or
2,3-dihydrofuran in the presence of tungstophosphoric acid (TPA) to
produce the corresponding pyrano- or furnaoquinolines.
The catalyst, TPA, is a commercially available important heteropoly
acid. In recent years, several heteropoly acids have gained much impor-
tance as catalysts for the synthesis of fine chemicals, flavones, and
[
16]
pharmaceuticals.
various useful industrial processes.
They are also frequently employed to conduct
Among the heteropolyacids,
[17,18]
polytungstic acids are most widely used as catalysts. In the present
conversion, tungstophosphoric acid has been found to be a highly
effective catalyst for the preparation of pyrano- and furanoquinolines.
In the absence of TPA, no products were formed under the present
experimental conditions.
In conclusion, we have applied heteropoly acid, TPA, at room
temperature for the convenient and efficient one-pot preparation of
pyrano- and furanoquinolines in excellent yields. The mild reaction
conditions, operational simplicity, and short reaction times are the
advantages of the present method.
CONCLUSION
In conclusion, we have developed a convenient and efficient method for
the synthesis of pyrano- and furanoquinolines using TPA as a heteroge-
neous catalyst. The method provides simple access for the preparation
of various pyrano- and furanoquinoline derivatives of biological
importance.

Pyrano- and Furanoquinoline Derivatives
EXPERIMENTAL
3829
General Procedure for the Synthesis of Pyrano- and Furanoquinolines
TPA (5 mol %) was added to a mixture of benzaldehyde (1 mmol) and
aniline (1.1 mmol) in MeCN (5 mL). The mixture was stirred at room
temperature for 10 min followed by addition of dihydropyran or dihydro-
furan (1.2 mmol). The stirring was continued, and the reaction was
monitored by thin-layer chromatography (TLC). After completion, the
reaction was quenched with water (5 ml), and the mixture was extracted
with CH Cl (3 ꢀ 5 ml). The combined organic layer was washed with
2
2
water (2 ꢀ 10 ml), dried, and concentrated. The residue was purified by
column chromatography to obtain pure pyrano- or furanoquinoline.
Spectral Data for Selected Compounds
1
The spectral ( H NMR and MS) and analytical data of the unknown
products are given here.
Product 4d (Table 2)
1
H NMR (CDCl , 200 MHz) d: 7.49–7.21 (5 H, m), 6.82 (1 H, dd, J ¼ 8.0,
3
2
.0 Hz), 6.71–6.60 (2H, m), 4.65 (1H, d, J ¼ 10.0 Hz), 4.45 (1 H, brs), 4.36
(
1 H, d, J ¼ 2.0 Hz), 4.06 (1H, m), 3.78 (3 H, s), 3.69 (1 H, m), 2.02 (1H,
þ
m), 1.92–1.28 (4H, m). FABMS m=z: 296 (M þ 1). Anal. calcd. for
C H NO :C, 77.29;H, 7.12; N, 4.75%. Found:C, 77.34; H, 7.24; N, 4.78%.
2
1
9
21
Product 5d (Table 2)
1
H NMR (CDCl , 200 MHz) d: 7.46–7.21 (5 H, m), 7.01 (1 H, dd, J ¼ 8.0,
3
2
.0 Hz), 6.72–6.60 (2 H, m), 5.30 (1 H, d, J ¼ 3.0 Hz), 4.66 (1 H, d,
J ¼ 2.0 Hz), 4.25 (1 H, brs), 3.84 (3 H, s), 3.52 (1 H, m), 3.41 (1 H, m),
þ
2
calcd. for C H NO : C, 77.29; H, 7.12; N, 4.75%. Found: C, 77.23;
.13 (1 H, m), 1.60–1.38 (4 H, m). FABMS m=z: 296 (M þ 1). Anal.
1
9
21
2
H, 7.18; N 4.82%.
Product 4j (Table 2)
1
H NMR (CDCl , 200 MHz) d: 7.54–7.21 (5 H, m), 6.97 (1 H, dd, J ¼ 8.0,
3
2
.0 Hz), 6.75–6.61 (2 H, m), 5.25 (1 H, d, J ¼ 10.0 Hz), 4.64 (1 H, d,

3830
B. Das et al.
J ¼ 2.5 Hz), 4.32 (1 H, brs), 3.82 (3 H, s), 3.80–3.62 (2 H, m), 2.74 (1 H,
þ
m), 2.21 (1 H, m), 1.52 (1 H, m). FABMS m=z: 282 (M þ 1). Anal. calcd.
for C H NO : C, 76.87; H, 6.76; N, 4.98%. Found: C, 76.73; H, 6.84; N,
2
1
8
19
4
.89%.
Product 5j (Table 2)
1
H NMR (CDCl , 200 MHz) d: 7.50–7.29 (5 H, m), 6.99 (1 H, dd, J ¼ 8.0,
3
2
.0 Hz), 6.74–6.62 (2 H, m), 4.60 (1 H, d, J ¼ 2.0 Hz), 4.58 (1 H, d,
J ¼ 3.0 Hz), 3.98 (1 H, m), 3.81 (3 H, s), 3.80–3.66 (2 H, m), 2.42 (1 H,
þ
m), 2.01 (1 H, m), 1.72 (1 H, m). FABMS m=z: 282 (M þ 1). Anal. calcd.
for C H NO : C, 76.87; H, 6.76; N, 4.98%. Found: C, 76.92; H, 6.79; N,
2
1
8
19
5
.06%.
Product 4l (Table 2)
1
H NMR (CDCl , 200 MHz) d: 7.42–7.27 (4 H, m), 6.83–6.74 (2 H,
3
m), 6.42 (1 H, m), 4.62 (1 H, d, J ¼ 10.0 Hz), 4.30 (1 H, d, J ¼ 2.0 Hz),
4
.01 (1 H, brs), 3.66 (1 H, m), 3.18 (1 H, m), 2.01 (1 H, m), 1.48–1.10
þ
(2 H, m). FABMS m=z: 304 306 (M þ 1). Anal. calcd. for
C H ClFNO: C, 67.33; H, 4.95; N, 4.62%. Found: C, 67.28; H,
1
7
15
4
.87; N, 4.71%.
Product 5l (Table 2)
1
H NMR (CDCl , 200 MHz) d: 7.40–7.28 (4 H, m), 7.11 (1 H, dd,
3
J ¼ 8.0, 2.0 Hz), 6.76 (1 H, m), 6.48 (1 H, m), 5.21 (1 H, d, J ¼ 3.0 Hz),
4
1
.61 (1 H, d, J ¼ 2.0 Hz), 3.58 (1 H, m), 3.37 (1 H, m), 2.07 (1 H, m),
þ
.53–1.41 (2 H, m). FABMS m=z: 304 306 (M þ 1). Anal. calcd. for
C H ClFNO: C, 67.33; H, 4.95; N, 4.62%. Found: C, 67.42; H,
15
1
7
4
.84; N, 4.68%.
Product 4n (Table 2)
1
H NMR (CDCl , 200 MHz) d: 7.45–7.23 (5 H, m), 6.91 (1 H, t,
3
J ¼ 8.0 Hz), 6.51 (1 H, d, J ¼ 8.0 Hz), 6.32 (1 H, d, J ¼ 8.0 Hz), 4.65
(
1 H, d, J ¼ 10.0 Hz), 4.42 (1 H, d, J ¼ 2.0 Hz), 4.10 (1 H, m), 3.94 (1 H,
brs), 3.64 (1 H, m), 2.32 (3 H, s), 2.0 (1 H, m), 1.91–1.25 (4 H, m). FABMS
m=z: 280 (M þ 1). Anal. calcd. for C H NO: C, 81.72; H, 7.53; N,
þ
1
9
21
5
.02%. Found: C, 81.95; H, 7.44; N, 5.11%.

Pyrano- and Furanoquinoline Derivatives
3831
Product 5n (Table 2)
1
H NMR (CDCl , 200 MHz) d: 7.49–7.21 (5 H, m), 6.99 (1 H, t,
3
J ¼ 8.0 Hz), 6.58 (1 H, d, J ¼ 8.0 Hz), 6.43 (1 H, d, J ¼ 8.0 Hz), 5.28
(
m), 3.30 (1 H, m), 2.38 (3 H, s), 2.24 (1 H, m), 1.81 (1 H, m), 1.52–1.23
1 H, d, J ¼ 3.0 Hz), 4.55 (1 H, d, J ¼ 2.0 Hz), 3.90 (1 H, brs), 3.52 (1 H,
þ
(
8
3 H, m). FABMS m=z: 280 (M þ 1). Anal. calcd. for C H NO: C,
1
9
21
1.72; H, 7.53; N, 5.02%. Found: C, 81.85; H, 7.64; N, 5.14%.
1
Product 4n (Table 2)
1
H NMR (CDCl , 200 MHz) d: 7.43–7.25 (5 H, m), 7.02 (1 H, d,
3
J ¼ 8.0 Hz), 6.49 (1 H, d, J ¼ 8.0 Hz), 6.25 (1 H, s), 4.63 (1 H, d,
J ¼ 10.0 Hz), 4.30 (1 H, d, J ¼ 2.0 Hz), 4.03 (1 H, m), 3.91 (1 H, brs),
3
.63 (1 H, m), 2.22 (3 H, s), 2.01 (1 H, m), 1.88–123 (4 H, m). FABMS
þ
m=z: 280 (M þ 1). Anal. calcd. for C H NO: C, 81.72; H, 7.53; N,
1
9
21
5
.02%. Found: C, 81.82; H, 7.61; N, 5.09%.
1
Product 5n (Table 2)
1
H NMR (CDCl , 200 MHz) d: 7.42–7.28 (5 H, m), 7.25 (1 H, d,
3
J ¼ 8.0 Hz), 6.60 (1 H, d, J ¼ 8.0 Hz), 6.39 (1 H, s), 5.27 (1 H, d,
J ¼ 3.0 Hz), 4.65 (1 H, d, J ¼ 2.0 Hz), 3.73 (1 H, brs), 3.55 (1 H, m), 3.41
(
1 H, m), 2.28 (3 H, s), 2.12 (1 H, m), 1.62–1.21 (4 H, m). FABMS m=z:
80 (M þ 1). Anal. calcd. for C H NO: C, 81.72; H, 7.53; N, 5.02%.
þ
2
Found: C, 81.68; H, 7.59; N, 5.07%.
1
9
21
ACKNOWLEDGMENTS
The authors thank the Council of Scientific and Industrial Research and
the University Grants Commission, New Delhi for financial assistance.
REFERENCES
1
. Johnson, J. V.; Rauckman, B. S.; Beccanari, P. D.; Roth, B. 2,4-Diamino-5-
benzylpyrimidines and analogs as antibacterial agents, 12: 1,2-Dihydroquino-
lylmethyl analogs with high activity and specificity for bacterial dihydrofolate
reductase. J. Med. Chem. 1989, 32, 1942.
2
. Yamada, N.; Kadowaki, S.; Takahashi, K.; Umeza, K. MY-1250, a major
metabolite of the anti-allergic drug repirinast, induces phosphorylation of a
78-kD a protein in rat mast cells. Biochem. Pharmacol. 1992, 44, 1211.

3832
B. Das et al.
3
. Wood, E.; Crosby, R. M.; Dickerson, S.; Frye, S. V.; Griffin, R.; Hunter, R.;
Jung, D. K.; McDonald, O. B.; McNutt, R.; Mahony, W. B.; Peel, M. R.;
Ray, J. A prodrug approach to the design of cRaf1 kinase anhibitors with
improved cellular activity. Anti-Cancer Drug Des. 2001, 16, 1.
. Ramesh, M.; Mohan, P. S.; Shanmugam, P. A convenient synthesis of
flindersine, atanine, and their analogues. Tetrahedron 1984, 40, 4041.
. Quraishi, M. A.; Thakur, V. R.; Dhawan, S. N. Synthesis of 6-(4-chlor
phenyl)-7H-indeno[2,1-C] quinolines and their biological activity. Indian J.
Chem. 1989, 28B, 891.
4
5
6
7
8
. Boger, D. L.; Weinreb, S. M. Hetero-Diels–Alder Methodology in Organic
Synthesis; Academic Press: San Diego, 1987; Chaps. 2 and 9.
. Weinreb, S. M. In Comprehensive Organic Synthesis; B. M. Trost, and I.
Fleming (Eds.); Pergamon, Oxford, 1991; vol. 5, p. 401.
. Babu, G.; Perumal, P. T. Convenient synthesis of pyrano[3,2-c] quinolines
and indeno[2,1-c] quinolines by imino Diels–Alder reaction. Tetrahedron
Lett. 1998, 39, 3225.
9
. Ma, Y.; Qian, C.; Xie, M.; Sun, J. Lanthanide chloride–catalyzed imino
Diels–Alder reaction one-pot synthesis of pyrano[3,2-c]-and furo[3,2-c]
quinolines. J. Org. Chem. 1999, 64, 6462.
1
0. Yadav, J. S.; Reddy, B. V. S.; Srinivas, R.; Madhuri, C.; Ramalingam, T.
Lithium perchlorate=diethylether–catalyzed aza-Diels–Alder reaction: An
expeditious synthesis of pyrano, indeno quinolines and phenanthridines.
Synlett 2001, 240.
1
1
1
1
1. Yadav, J. S.; Reddy, B. V. S.; Sunitha, V.; Reddy, K. S. Novel use of
Selectfluor for the synthesis of cis-fused pyrano- and furanotetrahydroquino-
lines. Adv. Synth. Catal. 2003, 345, 1203.
2. Zhou, Z.; Xu, F.; Han, X.; Zhou, J.; Shen, Q. Stereoselective synthesis of
pyrano[3,2-c]- and furano[3,2-c]quinolines: Samarium diiodide–catalyzed
one-pot aza-Diels–Alder reactions. Eur. J. Org. Chem. 2007, 5265.
3. Das, B.; Reddy, K. R.; Ramu, R.; Thirupathi, P.; Ravikanth, B. Iodine as an
efficient catalyst for one-pot multicomponent synthesis of b-acetamido
ketones. Synlett 2006, 1756.
4. Das, B.; Reddy, V. S.; Tehseen, F.; Krishnaiah, M. Catalyst-free highly regio-
and stereo-selective ring opening of epoxides and aziridines with sodium azide
using poly(ethylene glycol) as an efficient reaction medium. Synthesis 2007,
666.
1
5. Das, B.; Krishnaiah, M.; Balasubramanyam, P.; Veeranjaneyulu, B.; Kumar,
D. N. A remarkably simple N-formylation of anilines using polyethylene
glycol. Tetrahedron Lett. 2008, 49, 2225.
1
6. Pizzio, L. R.; C ꢀa ceres, C. V.; Blanco, M. N. Acid catalysts prepared by
impregnation of tungstophospohoric acid solutions on different supports.
Appl. Catal. A. 1998, 167, 283.
17. Soeda, H.; Okuhara, T.; Misono, M. Selective alkylation of p-xylene with
2-methylpropene by 12-tungstophosphoric acid. Chem. Lett. 1994, 909.
18. Kozhevnikov, I. V. Heteropoly acids and related compounds as catalysts for
fine chemical synthesis. Catal. Rev. Sci. Eng. 1995, 37, 311.