Synthesis of 2,4,5-triaryl-5H-chromeno[4,3-b]pyridines under microwave radiation

Article abstract of DOI:10.1002/jhet.98

(Chemical Equation Presented) 2,4,5-Triaryl-5H-chromeno[4,3-b]pyridines were synthesized from a three-component cascade reaction of 2′- hydroxyacetophenone, aromatic aldehyde, and ammonium acetate catalyzed by 2-1′-methylimidazolium-3-yl-1-ethyl sulfate u

Full text of DOI:10.1002/jhet.98

702
Synthesis of 2,4,5-Triaryl-5H-chromeno[4,3-b]pyridines
under Microwave Radiation
Vol 46
Hui Wu,a,b* Yu Wan,a,b Xiu-Mei Chen,a Cai-Fa Chen,b Lei-Lei Lu,c Hai-
Qiang Xin,a Hua-Hong Xu,a Li-Ling Pang,a
Rui Ma,a and Cai-Hui Yuea
aSchool of Chemistry and Chemical Engineering, Xuzhou Normal University,
Xuzhou 221116, People’s Republic of China
bKey Laboratory of Biotechnology on Medical Plant of Jiangsu Province, Jiangsu 221116,
People’s Republic of China
cDepartment of Chemical and Textile Engineering, Jiangyin Polytechnic College, Jiangyin,
Jiangsu 214405, People’s Republic of China
*E-mail: woo_hui@hotmail.com
Received June 4, 2008
DOI 10.1002/jhet.98
Published online 13 July 2009 in Wiley InterScience (www.interscience.wiley.com).
2,4,5-Triaryl-5H-chromeno[4,3-b]pyridines were synthesized from a three-component cascade reaction
of 20-hydroxyacetophenone, aromatic aldehyde, and ammonium acetate catalyzed by 2-10-methylimida-
zolium-3-yl-1-ethyl sulfate under microwave irradiation. Nine new bonds and two new rings were
formed in one-pot.
J. Heterocyclic Chem., 46, 702 (2009).
INTRODUCTION
pyridine (3, Fig. 1) [3c] were required. In another
method [4], it is the product of the primary 1,4-addition
followed by the pyrone ring-opening, attacking of the
NH2 group to the carbonyl bound with the aromatic
cycle and ring-closure involving the phenolic hydroxyl
and CHO group (Fig. 2).
The synthesis of new heterocyclic compounds has
been a subject of great interest due to their wide applic-
ability. Among a large variety of heterocyclic com-
pounds, heterocycles containing 5H-chromeno[4,3-b]pyr-
idine are of interest because they show some important
biological activities such as analgesic, anti-inflammation,
and antibacterial [1,2]. Accordingly, the development of
efficient synthetic strategies for the construction of this
molecular architecture is of considerable importance
from the standpoint of the material and organic
chemistry.
However, at least, two rings of product derived from
starting materials in these methods. There were few of
report about the synthesis of poly aryl-substituted 5H-
chromeno[4,3-b]pyridines. To the best of our knowl-
edge, aryl can improve the oil–water partition coefficient
of drug, which serve as an important impact factor on
the absorption and duration of drug in vivo, and it can
also lengthen the conjugated system to improve the ri-
gidity and luminescence potency of molecules. So, it is
important to develop new efficient method to prepare
poly aryl-substituted 5H-chromeno[4,3-b]pyridines.
The synthetic route used for the preparation of the
title compound (8) via the one-pot, three-component
reaction of aromatic aldehyde (6), 20-hydroxyacetophe-
none (7), and ammonium acetate (1:1:5) under micro-
wave-radiation is shown in Scheme 1. The new com-
pound, 2-10-methylimidazolium-3-yl-1-ethyl sulfate, was
By far, only two types of approach for obtaining 5H-
chromeno[4,3-b]pyridines have been reported due to its
complex structure. One was mainly based on the multi-
step intramolecular oxa- or diaza-Diels-Alder cycloaddi-
tions [1] with some shortcomings, such as low yields,
high reaction temperature (180–200ꢀC), long reaction
time (48h) [3c], and requirement of toxic solvents.
Moreover, unavailable starting material such as benzyli-
dene-3-chromanone-4 (1, Fig. 1) [3a] or neutral 2-aza-
dienes (2, Fig. 1) [3b] or 2-[2-(prop-2-ynyloxy)phenyl]-
C
V
2009 HeteroCorporation

July 2009
Synthesis of 2,4,5-Triaryl-5H-chromeno[4,3-b]pyridines under Microwave Radiation
703
Figure 1. Three previous starting materials of 5H-chromeno[4,3-b]
pyridines.
Figure 2.
pyridines.
A
previous method to construct 5H-chromeno[4,3-b]
synthesized and used as catalyst to improve the selectiv-
ity of the reaction. Upto nine new bonds were formed
with water as the only one by-product in this transfor-
mation. Only one benzene ring in the new 5H-chro-
meno[4,3-b]pyridine framework is derived from starting
material.
gated system with many modifiable positions, which
indicates its potential application in new drug discover
or molecular electronics.
A reasonable mechanism for the formation of the
products 8 was proposed (Scheme 2). The reaction pro-
ceeds via a simple and normal procedure: the tandem
Aldol condensation-Michael addition-Aldol condensa-
tion-nucleophilic addition (Adn), and finally, the elimi-
nation (E)-cyclication.
RESULTS AND DISCUSSION
In summary, we have developed a novel, simple, and
efficient method to synthesize 2,4,5-triaryl-5H-chro-
meno[4,3-b]pyridines under microwave radiation.
Besides the advantages that all the reactants were added
at the beginning and the same reaction conditions were
maintained throughout, the features of this process
include as follows: (1) the starting materials are avail-
able; (2) the reaction has good atom-economy and envi-
ronmental friendliness: nine new bonds (three CAN
bonds, one CAO bond, three CAC single bonds, two
CAC double bonds) and two new rings were formed in
one-pot with water as the only one by-product during
the whole process. Indeed, the present protocol provides
a straightforward and effective pathway to afford triaryl-
5H-chromeno[4,3-b]pyridines.
Initially, different reaction conditions were systemati-
cally tested based on the reaction of 4-cyanobenzalde-
hyde, 20-hydroxyacetophenone, and ammonium acetate
(1:1:5) (Table 1). It indicated that only the corresponding
chalcone was detected when the amount of 2-10-methyli-
midazolium-3-yl-1-ethyl sulfate was less than 3.2 mmol,
which showed the importance of catalyst amount in con-
trolling the selectivity of this multicomponent reaction. In
addition, glycol is necessary to prevent the instantaneous
partial charring of reactant caused by the catalyst. How-
ever, when the amount of glycol was up to 2 mL, the yield
decreased due to the dilution of catalyst.
Under the optimal conditions, the reaction of a variety
of aromatic aldehydes with 20-hydroxyacetophenone and
ammonium acetate was investigated. The product 8 was
obtained with the yields ranging from 50 to 81% (Table
2). As can be seen from the results, the electronic nature
and steric effect of substituted group in aromatic alde-
hyde influenced the yield. Substrates with electron-
donated groups can enhance the yields.
EXPERIMENTAL
Microwave radiation was carried out with a microwave
oven EmrysTM Creator from Personal Chemistry, Uppsala,
Sweden. Melting points were determined in the open capilla-
ries and were uncorrected. IR spectra were obtained on a
The X-ray structure of 8h [5] (Table 2, entry 8) was
shown in Figure 3. The framework has a long conju-
1
Bruker FT-IR spectrometer. H NMR spectra were recorded at
Scheme 1. One-pot synthesis of 2,4,5-triaryl-5H-chromeno[4,3-b]pyridines.
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

704
H. Wu, Y. Wan, X.-M. Chen, C.-F. Chen, L.-L. Lu, H.-Q. Xin, H.-H. Xu, L.-L. Pang, R. Ma,
and C.-H. Yue
Vol 46
Table 1
Testing of different reaction conditions based
on the model reaction.a
Amount
of catalyst
(mmol)
Amount
of glycol
(mL)
Time
(min)
Yield
(%)b
Entry
1
2
3
0.0
0.8
1.6
3.2
6.4
8.0
12.0
8.0
8.0
8.0
8.0
8.0
8.0
8.0
8.0
1.0
1.0
1.0
1.0
1.0
1.0
1.0
0.0
0.5
2.0
1.0
1.0
1.0
1.0
1.0
50
50
50
50
50
50
50
50
50
50
10
20
30
40
60
NPc
NP
NP
4
5
5
30
6
60
58
charring
charring
35
7
8
9
Figure 3. Single-crystal X-ray structure of compound 8h.
10
11
12
13
14
15
NP
NP
structure determination for complex 8h was given by Smarta-
pex Bruke diffractometer.
5
25
58
General procedure for the preparation of 2-10-methylimi-
dazolium-3-yl-1-ethyl sulfate. 1-Methylimidazole (0.3 mol)
and chloroethanol (0.3 mol) were added in a flask containing
10 mL of CHCl3, the mixture was refluxed for 8 h, removed
CHCl3 under vacuum, extracted the unreacted 1-methylimida-
zole with ether to give 1-methyl-3-(2-hydroxylethyl)imidazo-
lium chloride, then chlorosulfonic acid was added dropwise at
0–5ꢀC, when the mixture became solid, suitable single crystal
was obtained after 3 days by recrystallized with DMF. Its
structure was further confirmed by X-ray crystallographic anal-
ysis (Fig. 4). This solid inner salt reacted with chlorosulfonic
acid continuously until it just became a ropy liquid to afford
acidic ionic liquid 2-10-methylimidazolium-3-yl-1-ethyl sulfate.
Procedure for the preparation of triaryl-5H-chromeno
[4,3-b]pyridines. 2 mmol of aromatic aldehyde 1, 20-hydrox-
yacetophenone (2, 2 mmol), and ammonium acetate (5 equiv.)
were added into a one-necked 50 mL round bottom flask con-
taining 1 mL of glycol and 2 mL of 1-methyl-3-20-hydroxyle-
thylimidazolium chloride, the mixture was then radiated under
microwave in a EmrysTM Creator (Sweden) for 50 min (5 ꢁ
10 min). When the reaction was finished (monitored by TLC),
distilled water was poured into, the deposition was then fil-
tered, and recrystallized with DMF to give 8.
a Reaction conditions: 2.0 mmol of 4-cyanobenzaldehyde, 2.0 mmol of
20-hydroxyacetophenone, 5 equiv. of ammonium acetate, T ¼ 150ꢀC,
P ¼ 200 W.
b Isolated yield.
c No desired products.
400 MHz on a Bruker DPX 400 or AV400 spectrometer using
TMS as an internal standard and DMSO-d6 as solvent. 13C
NMR spectra were recorded at 100.6 MHz. Mass was deter-
mined by using a TOF-MS high-resolution mass spectrometer.
Elemental analyses were performed on a Perkin-Elmer-2400
elemental analyzer. Thin layer chromatography analysis was
carried out on aluminium sheets of silica gel GF254. All
reagents were obtained from commercial suppliers and used
without further purification unless otherwise stated. Organic
solvents were dried and/or distilled prior to use. The X-ray
Table 2
Synthesis of compounds 8 under microwave radiation.a
Entry
R
Product
Time (min)
Yield (%)b
2-(4,5-Diphenyl-5H-chromeno[4,3-b]pyridin-2-yl)phenol
(8a). This compound was obtained as yellow crystal (DMF),
mp 194.1–195.3ꢀC; ir (potassium bromide): 3310, 3030, 1600,
1
2
H
4-CH3
8a
8b
8c
8d
8e
8f
8g
8h
8i
50
50
50
50
50
50
50
50
50
50
50
50
50
50
65
68
71
52
68
49
42
60
70
45
63
40
56
55
1
1580, 1031; H NMR: d 13.80 (s, 1H, OH), 8.20 (d, 1H, J ¼
3
4-OCH3
4-Br
2,3-OCH3
4-CN
4-Cl
8.4 Hz, ArH), 8.14 (s, 1H, ArH), 8.01 (d, 1H, J ¼ 8.0 Hz,
ArH), 7.46 (m, 3H, ArH), 7.36 (m, 4H, ArH), 7.24 (m, 3H,
ArH), 7.11 (t, 1H, ArH), 7.04 (t, 2H, ArH), 7.02 (d, 1H, J ¼
9.6 Hz, ArH), 6.97 (t, 2H, ArH), 6.50 (s, 1H, CH); 13C NMR:
d 161.5, 159.2, 156.5, 153.2, 148.0, 141.2, 139.2, 135.0, 134.5,
131.5, 131.4, 131.3, 131.2, 131.0, 130.8, 130.3, 126.4, 125.5,
125.3, 124.5, 123.4, 122.9, 122.8, 120.9, 120.5; Anal. Calcd.
for C30H21NO2: C, 84.29; H, 4.95; N, 3.28. Found: C, 84.30;
H, 4.96; N, 3.26; hrms: m/z calcd. for C30H21NO2, 427.1572;
found, 427.1554.
4
5
6
7
8
9
2-OCH3
3,4,5-OCH3
2-Cl
10
11
12
13
14
8j
3-Br
2,4-Cl
8k
8l
3,4-(OCH2O)
3-NO2
8m
8n
2-(4,5-Bis(4-methylphenyl)-5H-chromeno[4,3-b]pyridin-2-yl)
phenol (8b). This compound was obtained as yellow crystal
(DMF), mp 207.7–208.7ꢀC; ir (potassium bromide): 3310,
3030, 2985, 1600, 1550, 1030; H NMR: d 14.70 (s, 1H, OH),
8.11 (dd, 1H, J1 ¼ 1.6 Hz, J2 ¼ 7.6 Hz, ArH), 7.85 (dd, 1H,
a Reaction conditions: 2.0 mmol aromatic aldehyde, 2.0 mmol 20-
hydroxyacetophenone, 5 equiv. of ammonium acetate, and 8.0 mmol
of catalyst in 1 mL of glycol, T ¼ 150ꢀC, P ¼ 200 W.
b Isolated yield.
1
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DOI 10.1002/jhet

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Synthesis of 2,4,5-Triaryl-5H-chromeno[4,3-b]pyridines under Microwave Radiation
705
Scheme 2. A possible mechanism for the formation of 8.
J1 ¼ 1.6 Hz, J2 ¼ 7.6 Hz, ArH), 7.80 (s, 1H, ArH), 7.33–7.37
(t, 1H, ArH), 7.24–7.28 (t, 1H, ArH), 7.18 (d, 2H, J ¼ 7.6 Hz,
ArH), 7.11–7.04 (m, 4H, ArH), 7.02 (s, 4H, ArH), 6.91–6.95
(t, 1H, ArH), 6.88–6.85 (dd, 1H, J1 ¼ 1.6 Hz, J2 ¼ 7.6 Hz,
ArH), 6.38 (s, 1H, CH), 2.39 (s, 3H, CH3), 2.25 (s, 3H, CH3);
13C NMR: d 159.9, 156.9, 154.2, 149.8, 145.9, 138.7, 138.2,
136.1, 134.1, 131.9, 131.6, 129.2, 129.1, 128.2, 127.9, 126.3,
124.2, 123.3, 22.2, 122.1, 119.2, 118.9, 118.8, 118.5, 118.1,
21.1, 21.0; Anal. Calcd. for C32H25NO2: C, 83.26; H, 6.77; N,
3.03. Found: C, 83.36; H, 6.76; N, 3.01; hrms: m/z calcd. for
C32H25NO2, 455.1885; found, 455.1871.
H, 3.26; N, 2.37; hrms: m/z calcd. for C30H19Br2NO2,
584.9762; found, 584.9760.
2-(4,5-Bis(2,3-dimethoxyphenyl)-5H-chromeno[4,3-b]pyri-
din-2-yl)phenol (8e). This compound was obtained as yellow
crystal (DMF), mp 223.7–225.2ꢀC; ir (potassium bromide):
1
3310, 3030, 2986, 1600, 1560, 1030; H NMR: d 13.95 (s, 1H,
OH), 8.23 (d, 1H, J ¼ 8.0 Hz, ArH), 8.15 (s, 1H, ArH), 8.00
(d, 1H, J ¼ 8.0 Hz, ArH), 7.33–7.41 (m, 2H, ArH), 7.13–7.18
(t, 1H, ArH), 6.10–7.08 (m, 6H, ArH), 6.84 (s, 1H, ArH), 6.77
(d, 1H, J ¼ 8.0 Hz, ArH), 6.46 (d, 1H, J ¼ 8.0 Hz, ArH),
6.44 (s, 1H, CH), 3.79 (s, 3H, OCH3), 3.67 (s, 3H, OCH3),
3.65 (s, 3H, OCH3), 3.52 (s, 3H, OCH3); 13C NMR: d 159.0,
155.3, 154.3, 153.0, 152.9, 147.0, 145.5, 145.0, 132.8, 132.3,
131.8, 131.0, 128.3, 124.8, 123.9, 122.9, 121.9, 121.6, 120.9,
119.9, 119.5, 118.5, 118.0, 61.0, 60.5, 56.5, 56.0; Anal. Calcd.
for C34H29NO6: C, 74.57; H, 5.34; N, 2.56. Found: C, 73.85;
H, 6.36; N, 2.51; hrms: m/z calcd. for C34H29NO6, 547.1995;
found, 547.1975.
2-(4,5-Bis(4-methoxyphenyl)-5H-chromeno[4,3-b]pyridin-
2-yl)phenol (8c). This compound was obtained as brown crys-
tal (DMF), mp 191.2–192.4ꢀC; ir (potassium bromide): 3310,
1
3030, 2985, 1610, 1540, 1020; H NMR: d 13.91 (s, 1H, OH),
8.18 (dd, 1H, J1 ¼ 1.6 Hz, J2 ¼ 7.6 Hz, ArH), 8.09 (s, 1H,
ArH), 8.00 (dd, 1H, J1 ¼ 1.6 Hz, J2 ¼ 7.6 Hz, ArH), 7.39–
7.32 (m, 2H, ArH), 7.26 (d, 2H, J ¼ 7.6 Hz, ArH), 7.12–7.17
(t, 1H, ArH), 6.90–7.07 (m, 7H, ArH), 6.79–6.81 (d, 2H, J ¼
7.6 Hz, ArH), 6.45 (s, 1H, CH), 3.78 (s, 3H, OCH3), 3.65 (s,
3H, OCH3); 13C NMR: d 160.0, 159.5, 156.9, 154.1, 149.4,
145.9, 132.0, 131.6, 131.3, 129.7, 129.4, 129.3, 126.3, 124.2,
123.5, 122.3, 122.1, 119.3, 118.9, 118.8, 118.5, 118.1, 114.0,
113.8, 55.3, 55.1; Anal. Calcd. for C32H25NO4: C, 78.83; H,
5.17; N, 2.87. Found: C, 78.72; H, 5.18; N, 2.89; hrms: m/z
calcd. for C32H25NO4, 487.1784; found, 487.1771.
2-(4,5-Bis(4-cyanophenyl)-5H-chromeno[4,3-b]pyridin-2-yl)
phenol (8f). This compound was obtained as yellow crystal
(DMF), mp > 300ꢀC; ir (potassium bromide): 3320, 3030,
1
2980, 2250, 1600, 1560, 1030; H NMR: d 13.50 (s, 1H, OH),
2-(4,5-Bis(4-bromophenyl)-5H-chromeno[4,3-b]pyridin-2-yl)
phenol (8d). This compound was obtained as yellow crystal
(DMF), mp 221.5–222.5ꢀC; ir (potassium bromide): 3310,
1
3030, 2980, 1600, 1550, 1010; H NMR: d 13.65 (s, 1H, OH),
8.21 (d, 1H, J ¼ 9.6 Hz, ArH), 8.15 (s, 1H, ArH), 8.06 (d, 1H,
J ¼ 9.6 Hz, ArH), 7.67 (d, 2H, J ¼ 8.0 Hz, ArH), 7.44 (d,
2H, J ¼ 9.6 Hz, ArH), 7.33–7.41 (m, 2H, ArH), 7.29 (d, 2H,
J ¼ 8.0 Hz, ArH), 7.14–7.21 (t, 1H, ArH), 6.94–7.09 (m, 5H,
ArH), 6.47 (s, 1H, CH); 13C NMR: d 155.2, 152.8, 149.1,
143.8, 141.4, 138.0, 135.0, 133.1, 131.0, 127.7, 127.3, 127.2,
127.0, 125.1, 124.9, 121.7, 119.6, 118.7, 118.3, 118.0, 117.6,
117.0, 114.4, 114.2, 113.9, 113.8, 113.4; Anal. Calcd. for
C30H19Br2NO2: C, 61.56; H, 3.27; N, 2.39. Found: C, 61.66;
Figure 4. Single-crystal X-ray structure of 2-10-methylimidazolium-3-
yl-1-ethyl sulfate.
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H. Wu, Y. Wan, X.-M. Chen, C.-F. Chen, L.-L. Lu, H.-Q. Xin, H.-H. Xu, L.-L. Pang, R. Ma,
and C.-H. Yue
Vol 46
8.21 (d, 1H, J ¼ 8.0 Hz, ArH), 8.19 (s, 1H, ArH), 8.03 (d, 1H,
J ¼ 7.6 Hz, ArH), 7.94 (d, 2H, J ¼ 8.0 Hz, ArH), 7.71 (d,
2H, J ¼ 8.0 Hz, ArH), 7.54 (d, 2H, J ¼ 8.0 Hz, ArH), 7.37–
7.41 (t, 2H, ArH), 7.30 (d, 2H, J ¼ 8.0 Hz, ArH), 7.17–7.21
(t, 1H, ArH), 6.96–7.04 (t, 3H, ArH), 6.57 (s, 1H, CH); 13C
NMR: d 159.2, 156.8, 154.0, 149.5, 148.3, 148.0, 147.9,
147.9, 145.7, 133.0, 132.9, 132.3, 130.3, 128.5, 124.0, 123.3,
123.0, 122.9, 122.2, 122.1, 121.9, 119.9, 119.8, 118.8, 118.2,
109.4, 109.0, 108.4, 101.9; Anal. Calcd. for C32H19N3O2: C,
80.49; H, 4.01; N, 8.80. Found: C, 80.59; H, 4.00; N, 8.78;
hrms: m/z calcd. for C32H19N3O2, 477.1477; found, 477.1455.
2-(4,5-Bis(4-chlorophenyl)-5H-chromeno[4,3-b]pyridin-2-yl)
phenol (8g). This compound was obtained as yellow crystal
(DMF), mp 208.3–209.4ꢀC; ir (potassium bromide): 3350,
NMR: d 159.21, 157.7, 153.8, 153.7, 147.2, 145.6, 135.2,
135.1, 133.4, 133.1, 132.4, 131.3, 131.2, 131.1, 131.1, 130.7,
130.3, 130.2, 130.0, 128.6, 127.9, 123.5, 119.7, 118.2; Anal.
Calcd. for C30H19Cl2NO2: C, 72.59; H, 3.86; N, 2.82. Found:
C, 72.66; H, 3.87; N, 2.80; hrms: m/z calcd. for
C30H19Cl2NO2, 495.0793; found, 495.0769.
2-(4,5-Bis(3-bromophenyl)-5H-chromeno[4,3-b]pyridin-2-yl)
phenol (8k). This compound was obtained as brown crystal
(DMF), mp 187.1–188.6ꢀC; ir (potassium bromide): 3320,
1
3020, 2980, 1620, 1580, 1020; H NMR: d 14.70 (s, 1H, OH),
8.10 (dd, 1H, J1 ¼ 1.6 Hz, J2 ¼ 7.6 Hz, ArH), 7.85 (dd, 1H,
J1 ¼ 1.6 Hz, J2 ¼ 7.6 Hz, ArH), 7.79 (s, 1H, ArH), 7.33–7.37
(t, 1H, ArH), 7.23–7.27 (t, 1H, ArH), 7.18 (d, 2H, J ¼ 7.6 Hz,
ArH), 7.01–7.11 (m, 8H, ArH), 6.90–6.94 (t, 1H, ArH), 6.82
(dd, 1H, J1 ¼ 1.6 Hz, J2 ¼ 7.6 Hz, ArH), 6.38 (s, 1H, CH);
13C NMR: d 159.2, 157.0, 154.2, 149.9, 145.7, 139.0, 137.0,
132.2, 129.7, 129.3, 129.1, 129.0, 129.0, 128.8, 128.5, 128.1,
124.1, 123.2, 123.0, 122.1, 121.1, 121.1, 119.8, 119.7, 118.6,
118.2; Anal. Calcd. for C30H19Br2NO2: C, 61.56; H, 3.27; N,
2.39. Found: C, 61.62; H, 3.26; N, 2.38; hrms: m/z calcd. for
C30H19Br2NO2, 584.9762; found, 584.9753.
1
3030, 2980, 1640, 1580, 1050; H NMR: d 13.62 (s, 1H, OH),
8.20 (d, 1H, J ¼ 8.0 Hz, ArH), 8.13 (s, 1H, ArH), 8.01 (d, 1H,
J ¼ 8.0 Hz, ArH), 7.52 (d, 2H, J ¼ 8.0 Hz, ArH), 7.29–7.35
(m, 6H, ArH), 7.11–7.20 (m, 3H, ArH), 6.94–7.04 (m, 3H,
ArH), 6.48 (s, 1H, CH); 13C NMR: d 159.1, 157.0, 153.9,
148.9, 145.9, 137.9, 135.8, 134.2, 134.0, 133.0, 132.8, 130.9,
130.0, 129.5, 129.0, 128.6, 124.0, 123.2, 123.0, 121.9, 121.0,
119.0, 118.9, 118.3; Anal. Calcd. for C30H19Cl2NO2: C, 72.59;
H, 3.86; N, 2.82. Found: C, 72.65; H, 3.85; N, 2.81; hrms: m/z
calcd. for C30H19Cl2NO2, 495.0793; found, 495.0775.
2-(4,5-Bis(2,4-dichlorophenyl)-5H-chromeno[4,3-b]pyridin-
2-yl)phenol (8l). This compound was obtained as yellow crys-
tal (DMF), mp 196.4–197.1ꢀC; ir (potassium bromide): 3310,
1
2-(4,5-Bis(2-methoxyphenyl)-5H-chromeno[4,3-b]pyridin-
2-yl)phenol (8h). This compound was obtained as yellow
crystal (DMF), mp 244.5–245.5ꢀC; ir (potassium bromide):
3030, 2998, 1600, 1540, 1020; H NMR: d 13.65 (s, 1H, OH),
8.21 (d, 1H, J ¼ 8.0 Hz, ArH), 8.15 (s, 1H, ArH), 8.02 (d, 1H,
J ¼ 8.0 Hz, ArH), 7.54 (d, 2H, J ¼ 8.0 Hz, ArH), 7.29–7.41
(m, 6H, ArH), 7.11–7.21 (m, 3H, ArH), 6.94–7.04 (m, 3H,
ArH), 6.50 (s, 1H, CH); 13C NMR: d 160.0, 159.5, 156.9,
154.1, 149.4, 145.9, 131.9, 131.6, 131.3, 129.7, 129.4, 129.3,
126.3, 124.2, 123.5, 122.3, 122.1, 119.3, 118.9, 118.2, 118.5,
118.1, 114.0, 113.7; Anal. Calcd. for C30H17Cl4NO2: C, 63.74;
H, 3.03; N, 2.48. Found: C, 63.66; H, 3.04; N, 2.50; hrms: m/z
calcd. for C30H17Cl4NO2, 564.9989; found, 564.9927.
1
3310, 3030, 2985, 1600, 1550, 1050; H NMR: d 14.70 (s, 1H,
OH), 8.11 (dd, J1 ¼ 1.2 Hz, J2 ¼ 1.6 Hz, 1H, ArH), 7.81 (dd,
J1 ¼ 1.6 Hz, J2 ¼ 1.6 Hz, 1H, ArH), 7.81 (s, 1H, ArH), 7.56
(t, 1H, ArH), 7.31–7.33 (t, 1H, ArH), 7.08–7.18 (m, 6H, ArH),
6.78–6.98 (m, 4H, ArH), 6.75–6.79 (m, 2H, ArH), 6.39 (s, 1H,
CH), 3.88 (s, 3H, OCH3), 3.74 (s, 3H, OCH3); 13C NMR: d
160.1, 159.7, 159.3, 156.9, 154.1, 149.8, 145.9, 132.9, 132.1,
131.1, 130.3, 129.6, 129.1, 128.0, 124.1, 123.6, 123.0, 122.5,
121.0, 119.9, 119.9, 118.5, 118.8, 114.8, 114.7, 60.5, 56.0;
Anal. Calcd. for C32H25NO4: C, 78.83; H, 5.17; N, 2.87.
Found: C, 78.91; H, 5.16; N, 2.85; hrms: m/z calcd. for
C32H25NO4, 487.1784; found, 487.1768.
2-(4-(Benzo[d][1,3]dioxol-5-yl)-5-(benzo[d][1,3]dioxol-6-yl)-
5H-chromeno[4,3-b]pyridin-2-yl)phenol (8m). This com-
pound was obtained as yellow crystal (DMF), mp 234.1–
235.0ꢀC; ir (potassium bromide): 3320, 3020, 2995, 1600,
1
1500, 1010; H NMR: d 13.85 (s, 1H, OH), 8.19 (d, 1H, J ¼
2-(4,5-Bis(3,4,5-trimethoxyphenyl)-5H-chromeno[4,3-b]
pyridin-2-yl)phenol (8i). This compound was obtained as
brown crystal (DMF), mp 236.1–237.9ꢀC; ir (potassium bro-
8.0 Hz, ArH), 8.09 (s, 1H, ArH), 7.81 (d, 1H, J ¼ 8.0 Hz,
ArH), 7.37 (t, 2H, ArH), 7.17 (t, 1H, ArH), 6.95–7.02 (m, 5H,
ArH), 6.73–6.81 (m, 3H, ArH), 6.46 (d, 1H, J ¼ 8.0 Hz,
ArH), 6.43 (s, 1H, ArH), 6.09 (s, 2H, CH2), 5.97 (s, 2H, CH2);
13C NMR: d 159.2, 156.9, 154.0, 152.9, 149.3, 148.2, 148.0,
147.9, 133.9, 123.6, 122.1, 120.0, 118.9, 109.3, 109.0, 108.0;
Anal. Calcd. for C32H21NO6: C, 74.56; H, 4.11; N, 2.72.
Found: C, 74.61; H, 4.10; N, 2.71; hrms: m/z calcd. for
C32H21NO6, 515.1369; found, 515.1360.
1
mide): 3300, 3030, 2980, 1600, 1550, 1050; H NMR: d 13.95
(s, 1H, OH), 8.22 (d, 1H, J ¼ 8.0 Hz, ArH), 8.17 (s, 1H,
ArH), 8.02 (d, 1H, J ¼ 8.0 Hz, ArH), 7.53–7.59 (t, 1H, ArH),
7.34–7.44 (m, 1H, ArH), 6.94–7.22 (m, 4H, ArH), 6.60 (s, 1H,
CH), 6.46 (d, 3H, J ¼ 11.2 Hz, ArH), 3.56–3.61 (m, 18H,
OCH3); 13C NMR: d 159.4, 156.9, 154.4, 153.9, 150.1, 147.6,
145.6, 138.2, 135.2, 132.8, 132.3, 131.6, 128.4, 127.7, 123.5,
123.6, 122.3, 121.0, 120.0, 119.6, 119.6, 118.6, 118.2, 106.6,
106.5, 106.1, 60.6, 60.5, 60.3, 56.9, 56.4, 56.0; Anal. Calcd.
for C36H33NO4: C, 71.16; H, 5.47; N, 2.31. Found: C, 71.26;
H, 5.46; N, 2.29; hrms: m/z calcd. for C36H33NO4, 607.2206;
found, 607.2217.
2-(4,5-Bis(3-nitrophenyl)-5H-chromeno[4,3-b]pyridin-2-yl)
phenol (8n). This compound was obtained as yellow crystal
(DMF), mp 186.2–197.7ꢀC; ir (potassium bromide): 3350,
1
3010, 2995, 1600, 1530, 1040; H NMR: d 14.35 (s, 1H, OH),
8.50 (m, 1H, ArH), 8.25–8.35 (m, 3H, ArH), 8.17 (s, 1H,
ArH), 8.00 (dd, 1H, J1 ¼ 1.6 Hz, J2 ¼ 7.6 Hz, ArH), 7.50–
7.67 (m, 2H, ArH), 7.10–7.49 (m, 9H, ArH), 6.55 (s, 1H, CH);
13C NMR: d 155.3, 153.6, 148.8, 141.7, 135.8, 133.5, 129.3,
128.7, 128.1, 127.7, 125.5, 125.1, 121.8, 119.9, 119.3, 119.2,
118.5, 117.9, 116.7, 116.6, 114.5, 114.3, 114.0, 113.5; Anal.
Calcd. for C30H19N3O6: C, 69.63; H, 3.70; N, 8.12. Found: C,
69.55; H, 3.71; N, 8.14; hrms: m/z calcd. for C30H19N3O6,
517.1274; found, 517.1360.
2-(4,5-Bis(2-chlorophenyl)-5H-chromeno[4,3-b]pyridin-2-yl)
phenol (8j). This compound was obtained as yellow crystal
(DMF), mp 196.9–197.7ꢀC; ir (potassium bromide): 3350,
1
3010, 2990, 1630, 1580, 1010; H NMR: d 13.62 (s, 1H, OH),
8.16–8.21 (t, 1H, ArH), 8.13 (s, 1H, ArH), 8.09 (d, 1H, J ¼
8.0 Hz, ArH), 7.67–7.75 (m, 1H, ArH), 6.81–7.49 (m, 12H,
ArH), 6.60 (d, 1H, J ¼ 9.6 Hz, ArH), 6.58 (s, 1H, CH); 13C
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

July 2009
Synthesis of 2,4,5-Triaryl-5H-chromeno[4,3-b]pyridines under Microwave Radiation
707
[4] (a) Haas, G.; Stanton, J. L.; Von Sprecher, A.; Wenk, P. J Het-
erocycl Chem 1981, 18, 607; (b) Ryabukhin, S. V.; Plaskon, A. S.; Voloch-
nyuk, D. M.; Tolmachev, A. A. Synlett 2004, 13, 2287; (c) Heber, D.
Synthesis 1978, 9, 691; (d) Abdel-Rahman, A. H.; Hammouda, M. A. A.;
El-Desoky, S. I. Heteroat Chem 2005, 16, 20; (e) Nohara, A.; Ishiguro, T.;
Sanno, Y. Tetrahedron Lett 1974, 15, 1183; (f) Coutinho, D. L. M.; Fer-
nandes, P. S. Indian J Chem 1992, 31B, 573; (g) Ghosh, C. K.; Khan, S.
Synthesis 1981, 11, 903; (h) Ghosh, C. K.; Ray, A.; Patra, A. J Heterocycl
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[5] The single crystal growth was carried out in DMF at room
temperature. X-ray crystallographic analysis was performed with a
Smartapex Bruke diffractometer (graphite monochromator, MoKa radi-
Acknowledgments. The authors are grateful to the foundation of
the ‘‘National Natural Sciences Foundation of China’’ (No.
20772103), the ‘‘Natural Science Foundation in Jiangsu Prov-
ince’’ (No.BK2007028), ‘‘Qing Lan Project in Jiangsu Province’’
(No.QL200607), and ‘‘Post-graduate creative project in Jiangsu
Province’’ (No.CX07S-016z) for financial support.
REFERENCES AND NOTES
[1] Paul, C. U.; Thomas, C.; David, T. C.; Thomas, G. H.;
Robert, G. M.; Steven, R. M.; Thomas, A. P.; Lawrence, D. W. J Med
Chem 1997, 40, 2688.
˚
ation k ¼ 0.71073 A). Crystal data for 8 h: Empirical formula
[2] Marta, C.; Filipe, A.; Luis, A.; Armando, V.; Fernanda, P.
J Org Chem 2008, 73, 1954.
C
32H25NO4, yellow, crystal dimension 0.16 ꢁ 0.10 ꢁ 0.08 mm, mono-
˚ ˚
clinic, space group P2(1)/n, a ¼ 10.382 (6) A, b ¼ 15.694 (9) A, c ¼
3
ꢀ
ꢀ
3
ꢀ
˚
˚
[3]
(a) Claude, M.; Fargeau, B.; Maitte, P. J Heterocycl Chem
14.987 (8) A, a ¼ 90.00 , b ¼ 99.233 (8) , c ¼ 90.00 , V ¼ 2410 (2) A ,
˚
1984, 21, 1549; (b) Stolle, W. A. W.; Frissen, A. E.; Marcelis, A. T. M.;
Plas, H. C. J Org Chem 1992, 57, 3000; (c) Palacios, F.; Alonso, C.;
Amezua, P.; Rubiales, G. J Org Chem 2002, 67, 1941; (d) Hammam, A.
E.-F. G.; Abd El-Salam, O. I.; Mohamed, A. M.; Hafez, N. A. Indian J
Chem 2005, 44B, 1887.
Mr ¼ 487.53, Z ¼ 7, Dc ¼ 1.344 Mg/m , k ¼ 0.71073 A, l (MoKa) ¼
0.088 mmꢂ1, F(000) ¼ 1024, S ¼ 0.898, R1 ¼ 0.0558, wR2 ¼ 0.0592.
Crystallographic data for the structures of 8 h reported in this letter have
been deposited with the Cambridge Crystallographic Date Centre as sup-
plementary publication No. CCDC-655835.
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet