One-pot synthesis of pyrano- and furanoquinolines catalyzed by molten tetra-n-butylphosphonium bromide under solvent-free conditions

Article abstract of DOI:10.1002/jhet.583

Molten tetra-n-butylphosphonium bromide is found to be a practical and inexpensive catalytic media for stereoselective one-pot synthesis of pyranoquinoline and furanoquinoline derivatives in good to excellent yields. Products of undesirable reactions resu

Full text of DOI:10.1002/jhet.583

484
One-Pot Synthesis of Pyrano- and Furanoquinolines Catalyzed by
Molten Tetra-n-butylphosphonium Bromide Under Solvent-Free
Conditions
Vol 48
Javad Salehi,a* Hojat Veisi,b* Mohammad M. Khodaei,c
and Ahmad R. Khosropourc
aDepartment of Pharmacology, Hamedan University of Medical Sciences, Hamedan, Iran
bDepartment of Chemistry, Payame Noor University (PNU), Iran
cDepartment of Organic Chemistry, Faculty of Chemistry, University of Razi, Kermanshah, Iran
*E-mail: javadsalehi_58@yahoo.com or hojatveisi@yahoo.com
Received March 28, 2010
DOI 10.1002/jhet.583
Published online 22 December 2010 in Wiley Online Library (wileyonlinelibrary.com).
Molten tetra-n-butylphosphonium bromide is found to be a practical and inexpensive catalytic media
for stereoselective one-pot synthesis of pyranoquinoline and furanoquinoline derivatives in good to
excellent yields. Products of undesirable reactions resulting from polymerization are not observed. The
use of this catalyst media avoids the use of any cocatalysts or toxic organic solvents.
J. Heterocyclic Chem., 48, 484 (2011).
INTRODUCTION
reaction media and catalyst can offer a solution to solvent
emission and catalyst recycle problems [10]. Ionic liquids
possess a number of interesting properties, especially their
lack of vapor pressure, a widely accessible temperature
range with lack of flammability, and ease of product recov-
ery that reduce environmental emissions [11].
Pyranoquinoline and furanoquinoline derivatives are
found abundantly in a variety of natural and synthetic
products, which exhibit various physiological properties
and are potentially bioactive compounds [1]. These skel-
etons exist in many alkaloids such as veprisine, oricine,
and flindersine [2], which possess a wide rang of biolog-
ical activity such as antiallergenic [3], antibacterial [4],
psychotropic [5], anti-inflammatory [6], and estrogenic
activity [7]. Hence, for the preparation of these complex
molecules, there has been interest in organic synthesis.
One of the most straightforward routs to their synthesis
involves imino-Diels–Alder reaction with various dieno-
philes in the presence of Lewis acids [4,8]. However,
the application of these methods suffers from some dis-
advantages such as the use of expensive or less easily
available reagents, vigorous reaction conditions, long
reaction times, unsatisfactory yields, low selectivity, or
the use of toxic solvents. On the other hand, many
Lewis acids are deactivated or sometimes decomposed
by nitrogen-containing reactants. Therefore, despite a
number of precedents, an efficient, practical, and facile
method for these transformations is desired.
Recently, ionic liquids have been successfully used as
solvents with catalytic activity for a variety of reactions
but their use as catalyst under solvent-free conditions
need to be more attention [12]. However, the high cost
of most conventional ionic liquids and apprehension
about their toxicity [13] especially imidazolium systems
with PF4 and BF4 anions are as toxic as benzene to cer-
tain aquatic ecosystems, and also liberate hazardous HF
during recycling have led us to explore the use of more
benign salts in the molten state as practical alternatives.
During our endeavors to explore the utility of ionic liq-
uid in organic transformations, we have recently
reported a practical and efficient protocol for thiolysis of
epoxides in the presence of tetra-n-butylphosphonium
bromide (TBPB) as an inexpensive and commercially
available ionic liquid [14].
RESULTS AND DISCUSSION
Due to the environmental concerns the use of benign sol-
vents as an alternative to volatile organic solvents are much
interest to organic chemists [9]. The use of ionic liquids as
In further extension of our work in the context of eco-
nomical chemistry [14], herein, we would like to report
C
V
2010 HeteroCorporation

March 2011
One-Pot Synthesis of Pyrano- and Furanoquinolines Catalyzed by Molten
Tetra-n-butylphosphonium Bromide Under Solvent-Free Conditions
485
Scheme 1
the use of molten tetra-n-butylphosphonium bromide
(m-TBPB) as an inexpensive ionic liquid for efficient
one-pot synthesis of pyrano- and furanoquinoline deriva-
tives under solvent-free conditions (Scheme 1).
one-pot synthesis of pyrano- and furanoquinolines, using
m-TBPB as a commercially available ionic liquid. The
significant feature of this method include (a) operational
simplicity, (b) inexpensive reagent, (c) high yields of
product, (d) high diastereoselectivity, and (e) the use of
relatively nontoxic catalytic media.
Several aldimines (formed in situ from aromatic alde-
hydes and anilines in ionic liquid) and 3,4-dihydro-2H-
pyran (DHP) or 2,3-dihydrofuran (DHF) were heated in
the presence of m-TBPB medium to afford the corre-
sponding pyrano- and furanoquinolines in 72–86% yield.
The high-yield transformation did not form any signifi-
cant amounts of undesirable side products. Among the
various ionic liquids such as tetra-n-butylammonium
bromide, tetra-n-butylammonium chloride, tetra-n-buty-
lammonium fluoride, and n-butylpyridinium tetrachloro-
ferrate ([bpy]FeCl4) which were studied for this reac-
tion, m-TBPB used here gave better yields (also better
selectivity) with short reaction times. However, in the
absence of ionic liquid, the reaction did not yield any
product even after a long reaction time (15–20 h). In all
cases, the products were obtained as a mixture of 3 exo-
and 4 endo-isomers favoring the endo-diastereomer 4.
On the other hand, this procedure is highly diastereose-
lective. The products were formed as a mixture of s-cis
and s-trans isomers, which could be separated by column
chromatography over silica gel and whose ratio was deter-
EXPERIMENTAL
General procedure for one-pot synthesis of pyrano- and fura-
noquinoline derivatives in the presence of m-TBPB under sol-
vent-free conditions. A mixture of aryl aldehyde (1 mmol), an-
iline derivative (1 mmol), and DHP or DHF (2 mmol) in m-
TBPB (1 mmol) was heated at 50ꢀC under stirring for the
appropriate time according to Table 1. The progress of the
reaction was monitored by thin layer chromatography (TLC)
(4:1, hexane/acetone) and after completion, it was poured into
cooled mixture of (1:1) water/ethanol and stirred for 5 min.
The solid was suction filtered, washed with cold ethanol (2 ꢁ
10 mL), and filtered. The resulting product was directly
charged on small silica gel column and eluted with a mixture
of acetone/n-hexane (1:4) to afford pure products.
Analytical data for selected compounds.
Product
1. Trans: mp: 123–124ꢀC; 1H-NMR (CDCl3), d (ppm): 7.25–
7.45 (6H, m), 7.05 (1H, t, J ¼ 7.8 Hz), 6.75 (1H, t, J ¼ 7.8
Hz), 6.55 (1H, d, J ¼ 7.8 Hz), 5.34 (1H, d, J ¼ 5.6 Hz), 4.70
(1H, d, J ¼ 2.8 Hz), 3.35–3.65 (3H, m), 2.15 (1H, m), 1.25–
1.55 (4H, m); 13C-NMR (CDCl3), d (ppm): 145.2, 141.1,
128.3, 128.0, 127.6, 127.5, 126.8, 119.8, 118.3, 114.4, 72.8,
60.6, 59.3, 38.9, 25.4, 18.0; ir (KBr), m (cmꢂ1): 3378, 2936,
1605, 1485, 1071, 750.
1
mined by H-NMR spectra of the crude products. The
results shown in Table 1 clearly indicate the scope and
generality of diasteroselective condensation with respect
to various aryl aldehydes and anilines with DHP or DHF.
The reaction is fairly general, clear, rapid, and effi-
cient. The experimental procedure for this transforma-
tion is remarkably straightforward and unlike previously
reported methods, the presence procedure does not
require the use of toxic organic solvents or inert atmos-
pheres. The proposed mechanism of formation of quino-
line is shown in Scheme 2, being similar to that previ-
ously suggested [10c].
Cis: colorless solid, mp: 94–95ꢀC; 1H-NMR (CDCl3), d
(ppm): 7.35–7.45 (5H, m), 7.25 (1H, d, J ¼7.8 Hz), 7.05 (1H,
t, J ¼ 7.8 Hz), 6.80 (1H, t, J ¼ 7.8 Hz), 6.50 (1H, d, J ¼ 7.8
Hz,), 4.75 (1H, d, J ¼ 10.5 Hz), 4.40 (1H, d, J ¼ 2.8 Hz),
3.95 (2H, m), 3.75 (1H, t, J ¼ 11.7 Hz), 2.15 (1H, m),
1.85(1H, m), 1.65 (1H, m), 1.50 (1H, m), 1.25 (1H, m); 13C-
NMR (CDCl3), d (ppm): 144.1, 141.7, 130.2, 128.7, 128.0,
127.2, 127.1, 120.0, 116.8, 113.5, 73.9, 68.0, 54.1, 38.2, 23.5,
21.4; ir (KBr), m (cmꢂ1): 3374, 2928, 1610, 1489, 1077, 750.
1
Product 2. Trans: colorless solid, mp: 154–155ꢀC; H-NMR
(CDCl3), d (ppm): 7.37–7.28 (6H, m), 7.03 (1H, d, J ¼ 8.2
Hz), 6.53 (1H, d, J ¼ 8.3 Hz), 5.24 (1H, brs), 4.64 (1H, brs),
3.89 (1H, brs), 3.61 (1H, d, J ¼ 11.2 Hz), 3.43–3.31 (1H, m),
2.13–2.07 (1H, m), 1.78–1.31 (4H, m); 13C-NMR (CDCl3), d
(ppm): 145.6, 141.3, 128.1, 128.0, 127.3, 127.1, 126.8, 119.3,
118.0, 114.4, 72.7, 60.5, 59.0, 38.2, 25.4, 18.2; ir (KBr), m
CONCLUSIONS
In conclusion, we have demonstrated a new, straight-
forward, efficient, and stereoselective method for the
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

486
J. Salehi, H. Veisi, M. M. Khodaei, and A. R. Khosropour
Vol 48
Table 1
One-pot synthesis of pyrano- and furanoquinoline in the presence of m-TBPB under solvent-free conditions.
Entry
Producta
Time (h)
1.25
Yield (%)b
79
trans/cisc
95/5
de%
90
1
2
3
4
5
6
1.30
1.30
1.30
1.15
1.30
81
72
78
85
73
93/7
86
84
86
76
70
92/8
93/7
88/12
85/15
7
1.15
83
90/10
80
8
1
82
96/4
92
(Continued)
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

March 2011
One-Pot Synthesis of Pyrano- and Furanoquinolines Catalyzed by Molten
Tetra-n-butylphosphonium Bromide Under Solvent-Free Conditions
487
Table 1
(Continued)
Entry
9
Producta
Time (h)
1.10
Yield (%)b
86
trans/cisc
90/10
de%
80
10
11
12
1.40
80
85
85
88/12
90/10
92/8
75
90
80
1
1.15
a All products were characterized with 1H-NMR, 13C-NMR, IR, and comparison of their physical and spectral data with those samples in the
literatures.8
b Isolated yields.
c The isomeric ratio is based on isolation by column chromatography.
Scheme 2
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

488
J. Salehi, H. Veisi, M. M. Khodaei, and A. R. Khosropour
Vol 48
(cmꢂ1): 3362, 3326, 2937, 1615, 1487, 1071, 920, 820, 800,
750, 700.
Product 9. Trans: solide, mp: 160–161ꢀC; 1H-NMR
(CDCl3), d (ppm): 8.29 (2H, d), 7.78 (2H, d), 7.41 (1H, d), 7.1
(1H, d), 6.6 (1H, s), 4.65 (1H, d, J ¼ 5.0 Hz), 4.28 (1H, m),
3.75–3.32 (3H, m), 2.25 (1H, m), 2.2 (1H, m), 1.65 (1H, m);
13C-NMR (CDCl3), d (ppm): 148, 145, 132.2, 129.3, 128.3,
125.1, 124, 122.3, 117, 115, 63.2, 54, 40.1, 27.3, 21.2; ir
(KBr), m (cmꢂ1): 3360,2931,1495,1261, 900, 800,750,700.
Cis: colorless solid, mp 122–123ꢀC; 1H-NMR (CDCl3), d
(ppm): 7.37 (5H, m), 7.19 (1H, s), 7.03 (1H, d, J ¼ 8.3 Hz),
6.45 (1H, d, J ¼ 8.3 Hz), 4.67 (1H, d, J ¼ 10.5 Hz), 4.33
(1H, s), 4.08 (2H, m), 3.73 (1H, m), 2.05 (1H, m), 1.83–1.31
(4H, m); 13C-NMR (CDCl3), d (ppm): 143.2, 141.8, 130.3,
129.1, 128.6, 127.6, 126.1, 121.8, 121.7, 115.2, 73.8, 68.4,
54.8, 38.6, 23.9, 22.0; ir (KBr), m (cmꢂ1): 3348, 2934, 1494,
1265, 920, 825, 810, 750, 700.
Acknowledgments. The authors are thankful to Razi University
Research Council, Pharmacology Department of Medical Univer-
sity Hamedan, and Payame Noor University for partial support of
this work.
1
Product 5. Trans: colorless solid, mp: 146–147ꢀC; H-NMR
(CDCl3), d (ppm): 7.40–7.29 (5H, m), 7.03 (1H, s), 6.73 (1H,
d, J ¼ 8.2 Hz), 6.57 (1H, d, J ¼ 8.2 Hz), 5.31 (1H, d, J ¼ 5.4
Hz), 4.61 (1H, s), 3.73 (3H, s), 3.67 (1H, brs), 3.61–3.36 (2H,
m), 2.15 (1H, m), 1.54–1.26 (4H, m); 13C-NMR (CDCl3), d
(ppm): 152.8, 141.3, 139.1, 128.3, 127.4, 126.8, 121.1, 115.7,
115.0, 111.8, 72.9, 60.8, 59.5, 55.8, 39.1, 25.3, 17.9; ir (KBr),
m (cmꢂ1): 3295, 2942, 1502, 1262, 1065, 921, 825, 810, 735,
710.
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Cis: dense liquid, 1H-NMR (CDCl3), d (ppm): 7.43–7.27
(5H, m), 6.82 (1H, s), 6.75 (1H, d, J ¼ 9.1 Hz), 6.49 (1H, d, J
¼ 8.5 Hz), 4.62 (1H, d, J ¼ 10.5 Hz), 4.38 (1H, s), 4.10 (1H,
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121.3, 116.7, 115.5, 114.7, 74.5, 68.3, 55.7, 55.1, 38.8, 24.0,
21.9; ir (neat), m (cmꢂ1): 3361, 2938, 1504, 1255, 1032, 920,
825, 810, 735, 710.
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1
Product 6. Trans: solid, mp: 146–147ꢀC; H-NMR (CDCl3),
d (ppm): 7.32 (2H, d, J ¼ 8.0 Hz), 7.18 (1H, d, J ¼ 8.0 Hz),
7.04 (1H, t, J ¼ 8.0 Hz), 6.84 (2H, d, J ¼ 8.0 Hz), 6.64 (1H,
t, J ¼ 8.0 Hz), 6.45 (1H, d, J ¼ 8.0 Hz), 4.64 (1H, d, J ¼ 10
Hz), 4.36 (1H, d, J ¼ 2.5 Hz), 4.06 (1H, m), 3.97 (1H, d, J ¼
3.0 Hz), 3.82 (3H, s), 3.63 (1H, t, J ¼ 10.0 Hz), 2.02 (1H, m),
1.82 (1H, m), 1.64 (1H, m), 1.44 (1H, m), 1.28 (1H, m).
Cis: solid, mp: 154–155ꢀC; 1H-NMR (CDCl3), d (ppm):
7.38 (1H, d, J ¼ 8.0 Hz), 7.30 (2H, d, J ¼ 8.0 Hz), 7.00 (1H,
m), 6.82 (2H, d, J ¼ 8.0 Hz), 6.77 (1H, t, J ¼ 8.0 Hz), 6.50
(1H, d, J ¼ 8.0 Hz), 5.26 (1H, d, J ¼ 3.0 Hz), 4.60 (1H, d, J
¼ 3.0 Hz), 3.84 (1H, m), 3.82 (3H, s), 3.58 (1H, m), 3.22 (1H,
m), 2.04 (1H, m), 1.58–1.30 (4H, m).
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1
Product 7. Trans: solid, mp: 147–148ꢀC; H-NMR (CDCl3),
d (ppm): 7.35 (4H, s), 7.14 (1H, d, J ¼ 7.8 Hz), 7.05 (1H, t, J
¼ 7.8 Hz), 6.64 (1H, d, J ¼ 8.0 Hz), 6.42 (1H, d, J ¼ 8.0
Hz), 4.58 (1H, d, J ¼ 5.0 Hz), 4.08 (1H, m), 3.85 (3H, m),
2.45 (1H, m), 2.0 (1H, m), 1.72 (1H, m); ir (KBr), m (cmꢂ1):
3379, 2940, 1495, 1261, 810, 750.
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1
Cis: solid, mp: 152–153ꢀC; H-NMR (CDCl3), d (ppm): 7.4
(1H, d, J ¼ 7.8 Hz), 7.36 (4H, s), 7.05 (1H, t, J ¼ 7.8 Hz),
6.68 (1H, t, J ¼ 7.8 Hz), 6.56 (1H, d, J ¼ 7.8 Hz), 5.25 (1H,
d, J ¼ 8.0 Hz), 4.65 (1H, d, J ¼ 3 Hz), 3.78 (1H, brs), 3.40–
3.62 (2H, m), 2.18 (1H, m), 1.56 (2H, m); ir (KBr), m (cmꢂ1):
3345, 2931, 1492, 1265, 815, 750.
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1
Product 8. Trans: solid, mp: 155–156ꢀC; H-NMR (CDCl3),
d (ppm): 8.31 (2H, d), 7.81 (2H, d), 7.4 (1H, d), 7.2 (1H, t),
6.91 (1H, t), 6.7 (1H, d), 5.4 (1H, d), 4.9 (1H, m), 3.81–3.89
(3H, m), 2.81–2.92 (1H, m), 2.1–2.3 (1H, m), 1.65 (1H, m);
13C-NMR (CDCl3), d (ppm): 147.0, 144, 131.0, 129.2, 127.3,
125.4, 124, 122, 120.1, 115, 68, 58, 54, 47, 25; ir (KBr), m
(cmꢂ1): 3296, 2940, 1480, 1072, 750, 800.
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Journal of Heterocyclic Chemistry
DOI 10.1002/jhet