An efficient one-pot synthesis of 1-amino-3-cyano-4-aryl-10- ethoxycarbonylazuleno[2,1-b]pyrans

Article abstract of DOI:10.3987/COM-11-12406

An efficient and easy method for the one-pot three-component synthesis of 2-amino-3-cyano-4-aryl-10-ethoxycarbonylazuleno[2,1-b]pyran derivatives by the three-componenet condensation of ethyl 2-hydroxyazulene-1-carboxylate, aldehydes, and malononitrile in

Full text of DOI:10.3987/COM-11-12406

HETEROCYCLES, Vol. 85, No. 2, 2012
441
HETEROCYCLES, Vol. 85, No. 2, 2012, pp. 441 - 448. © 2012 The Japan Institute of Heterocyclic Chemistry
Received, 3rd December, 2011, Accepted, 26th December, 2011, Published online, 10th January, 2012
DOI: 10.3987/COM-11-12406
AN EFFICIENT ONE-POT SYNTHESIS OF 1-AMINO-3-CYANO-
4-ARYL-10-ETHOXYCARBONYLAZULENO[2,1-b]]PYRANS
Dao-lin Wang,* Shan-Shan Feng, Qing-Tao Cui, and Jia-Yi Yu
Liaoning Key Laboratory of Synthesis & Application of Functional Compound,
College of Chemistry & Chemical Engineering, Bohai University, Jinzhou
121001, P. R. China
Abstract — An efficient and easy method for the one-pot three-component
synthesis of 2-amino-3-cyano-4-aryl-10-ethoxycarbonylazuleno[2,1-b]pyran
derivatives
by
the
three-componenet
condensation
of
ethyl
2-hydroxyazulene-1-carboxylate, aldehydes, and malononitrile in the presence of
diazabicyclo[2.2.2]octane (DABCO) has been described.
It is well known that pyrans are important core units in a number of natural products1 and photochromic
materials.2 Compounds with pyran ring system have many pharmacological properties and play important
roles in biochemical process. Moreover, 4H-pyrans are useful intermediates for the synthesis of various
compounds.3,4 Therefore, preparation of this heterocyclic nucleus has gained great importance in organic
synthesis.
The azulene constitute was the best known of polycyclic nonbenenoid aromatic compounds and have long
fascinated chemists with their beautiful colors and unusual electronic properties.5 Azulenes have attracted
interest in medicine as antiulcer drugs6 anticancer agents,7 and as antioxidant therapeutics for
neurode-generative conditions.8 A variety of heteroarylazulenes have so far been obtained on the
viewpoints of chemical properties and physiological activities by several methods.9 Recently, our group
has developed several synthesis method s of heteroarylazulenes.10 In this work, we report one-pot
synthesis of 2-amino-3-cyano-4-aryl-10-ethoxycarbonylazuleno[2,1-b]pyrans by condensation of ethyl
2-hydroxyazulene-1-carboxylate (1), aldehydes (2a), and malononitrile using inexpensive and convenient
available diazabicyclo[2.2.2]octane (DABCO) as catalyst (Scheme 1).

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HETEROCYCLES, Vol. 85, No. 2, 2012
EtO2C
CO2Et
O
R
NH2
CN
OH
CN
+
DABCO
R-CHO
+
CN
EtOH
reflux
1
2
3
4
Scheme 1
In this three-component reaction, we found that catalysts had significant effects on the reaction time and
yields (Table 1). The results indicated that this reaction could not take place in the presence of proton
acids and classical Lewis acids as catalysts in EtOH under reflux conditions for 120 min, such as TsOH,
NH2SO3H, CF3CO2H, ZnCl2, and MgCl2 (Table 1, entries 1-5). Then, we carried out the reaction using
bases as the catalysts under the same reaction conditions, such as Et3N, DBU, piperidine and DABCO
(Table 1, entries 6-11). To our delight, the desired condensation product 4a was obtained in moderate to
excellent yields (45-92%), which meant that this three-component condensation reaction of ethyl
2-hydroxyazulene-1-carboxylate (1), benzaldehyde (2a), and malononitrile (3) could proceed smoothly
catalyzed by bases. Furthermore, we found that the yields of 4a were improved as the amount of DABCO
increased from 10 to 20%, and the yields plateaued when the amount of DABCO was further increased to
30% (Table 1, entry 11). Therefore, 20 mol% of DABCO was considered to be the most suitable.
Table 1. Condensation of ethyl 2-hydroxyazulene-1-carboxylate (1), benzaldehyde (2a), and
malononitrile (3) using various catalystsa a
EtO2C
CO2Et
O
NH2
CHO
OH
CN
CN
3
DABCO
+
CN
+
1
2
4
Time
Yieldb
(%)
Amount of Catalyst
(mol%)
Entry
Catalyst
(min)
120
120
120
120
120
90
60
60
60
60
60
20
20
20
20
20
20
20
20
10
20
30
0
0
0
0
0
45
57
72
78
92
90
(84%) c
(92%)
(66%)
(98%)
(90%)
1
2
3
4
5
6
7
8
TsOH
NH2SO3H
CF3CO2H
ZnCl2
MgCl2
Et3N
DBU
piperidine
DABCO
DABCO
DABCO
9
10
11
a Reaction conditions: 1-cyanoacetylguaiazulene 1 (1 mmol), benzaldehyde 2a (1.1 mmol), malononitrile 3 (1.1 mmol),
EtOH (15 mL).
b Isolated yields.
c Recovery.

HETEROCYCLES, Vol. 85, No. 2, 2012
443
Furthermore, the reaction was optimized by screening the solvent such as CH2Cl2, CH2ClCH2Cl, THF,
MeCN, AcOH, EtOH, toluene and DMF. The reaction using DMF and EtOH as the solvents gave the
corresponding product 4a in high yields and in short reaction time. From the economical and
environmental point of view, EtOH was chosen as the reaction medium for all further reactions. Therefore,
the best reaction conditions were obtained by using 20 mol % of ammonium acetate as the catalyst in
EtOH at reflux temperature.
A series of aromatic and heterocyclic aldehydes were selected to undergo the condensation in the
presence of DABCO. As shown in Table 2, aromatic aldehydes (2) carrying either electron-donating or
electron-withdrawing substituents reacted efficiently giving excellent yields (Table 2, entries 1-12).
Hence, the effect of the nature of the substituents on the aromatic ring showed no obvious effect on this
conversion. Furthermore, heterocyclic aldehydes could react smoothly to give the corresponding products
4 in good yields (Table 2, entries 13, 14).
Table 2. Synthesis of compounds 4 catalyzed by DABCO
Entry
2 /R
C6H5
2b 4-MeC6H4
2c 4-MeOC6H4
2d 4-ClC6H4
Time /min
Product
Yield /%
1
2
3
4
5
6
7
8
9
10
11
12
13
14
2a
60
60
40
40
60
90
50
50
40
40
40
60
50
50
4a
4b
4c
4d
4e
4f
4g
4h
4i
4j
4k
4l
4m
4n
92
87
94
90
86
88
89
93
90
90
94
80
82
86
2e
2f
2g
4-FC6H4
4-HOC6H4
2-MeOC6H4
2h 2-HOC6H3
2i
2j
2k
2,4-(MeO)2C6H3
3,4-(MeO)2C6H3
3-MeO,4-HOC6H3
2l
3-NO2C6H4
2m
2-Furyl
2n 2-Thienyl
We propose a mechanism of the DABCO-catalyzed condensation as shown in Scheme 2. The condensa-
tion of ethyl 2-hydroxyazulene-1-carboxylate 1, aldehyde 2, malononitrile 3 may occur by a mechanism
of Knoevenagel condensation, Michael addition, intramolecular cyclization, and tautomerization. Initially,
intermediate 5 is formed by Knoevenagel condensation of aldehyde 2 and malononitrile 3 by the action of

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HETEROCYCLES, Vol. 85, No. 2, 2012
CN
CN
R
CN
CN
DABCO
Knoevenagel
condensation
R-CHO
+
2
5
3
H DABCO
EtO2C
CO2Et
O
CN
OH
cyclization
DABCO
+
5
CN
Michael addition
R
1
6
DABCO
H
EtO2C
EtO2C
NH2
CN
O
R
O
N
tautomerization
-DABCO
CN
R
7
4
Scheme 2
DABCO. In the presence DABCO, Michael addition of ethyl 2-hydroxy azulene-1-carboxylate 1 on 5
leads to form intermediate 6, followed by intramolecular cyclization and tautomerization, affords the
correspondding products 4 (Scheme 2). We think that DABCO serves as a base as well as a proton shuttle
to promote this reaction.
In conclusion, the present method discloses a new and simple modification of the condensation of ethyl
2-hydroxyazulene-1-carboxylate 1, aldehyde 2, malononitrile 3 to the synthesis of 2-amino-3-cyano-4-
aryl-10-ethylcarbonyl azuleno[2,1-b]pyran derivatives 4 by using DABCO as a catalyst in EtOH. The
operational simplicity, mild reaction conditions, short reaction time, and little environmental impact are
notable features of this procedure.
EXPERIMENTAL
1
All melting points were determined on a Yanako MP-3 apparatus and are uncorrected. HNMR spectra
were recorded on a Bruker spectrometer (400 MHz). IR spectra were measured on Shimadzu IR-740
spectrophotometer. Elemental analyses were performed on EA 2400Ⅱ elemental analyzer
(Perkin-Elmer).

HETEROCYCLES, Vol. 85, No. 2, 2012
445
Preparation of 2-amino-3-cyano-4-aryl-10-ethoxycarbonyl azuleno[2,1-b]pyran derivatives.
General procedure: A mixture of ethyl 2-hydroxyazulene-1-carboxylate11 (1, 1.0 mmol), aldehyde (2,
1.1 mmol), malononitrile (3, 1.1 mmol), and DABCO (0.3 mmol) in EtOH (15 mL) was heated to reflux
under stirring for the given time (Table 2). After completion (by TLC), the reaction mixture was cooled to
room temperature, then water (10 mL) was added to the mixture and stirred for 5 min. The solid was
filtered and recrystallized to afford the corresponding products. The physical and spectra data of the
compounds 4a-n are as follows:
2-Amino-3-cyano-4-phenyl-10-ethoxycarbonylazuleno[2,1-b]pyran (4a): Deep red prism (from EtOH).
mp 198-200 ºC; IR (KBr, cm-1): ν 3280 (NH2), 2216 (CN), 1628 (C=O). 1H-NMR (CDCl3): δ 1.26 (3H, t,
J = 7.2 Hz, OCH2CH3), 4.59 (2H, q, J = 7.2 Hz, CO2CH2CH3), 4.94 (2H, s, NH2), 5.28 (1H, s, CH),
7.30-7.33 (2H, m), 7.37-7.43 (4H, m), 7.57 (1H, dd, J = 9.6, 10.0 Hz), 7.69 (1H, dd, J = 9.6, 9.6 Hz), 7.99
(1H, d, J = 9.6 Hz), 9.64 (1H, d, J = 10.0 Hz). Anal. Calcd for C23H18N2O3: C 74.58, H 4.90, N 7.56.
Found: C 74.67, H 5.13, N 7.68.
2-Amino-3-cyano-4-(4-methylphenyl)-10-ethoxycarbonylazuleno[2,1-b]pyran (3b): Deep red prism
(from EtOH). mp 192-194 ºC; IR (KBr, cm-1): ν 3312 (NH2), 2209 (CN), 1631 (C=O). 1H-NMR (CDCl3):
δ 1.25 (3H, t, J = 7.2 Hz, OCH2CH3), 2.28 (3H, s, CH3), 4.47 (2H, q, J = 7.2 Hz, CO2CH2CH3), 4.75 (2H,
s, NH2), 5.29 (1H, s, CH), 7.08 (4H, m), 7.30 (1H, dd, J = 9.6, 10.2 Hz), 7.56 (1H, dd, J = 9.6, 9.6 Hz),
7.66 (1H, dd, J = 9.6, 9.6 Hz), 7.90 (1H, d, J = 10.0 Hz), 9.53 (1H, d, J = 10.0 Hz). Anal. Calcd for
C24H20N2O3: C 74.98, H 5.24, N 7.29. Found: C 74.74, H 5.37, N 7.31.
2-Amino-3-cyano-4-(4-methoxyphenyl)-10-ethoxycarbonylazuleno[2,1-b]pyran (3c): Deep red prism
(from EtOH). mp 185-187 ºC; IR (KBr, cm-1): ν 3322 (NH2), 2215 (CN), 1642 (C=O). 1H-NMR (CDCl3):
δ 1.25 (3H, t, J = 7.2 Hz, OCH2CH3), 3.85 (3H, s, OCH3), 4.59 (2H, q, J = 7.2 Hz, CO2CH2CH3), 4.88
(2H, s, NH2), 5.25 (1H, s, CH), 6.91 (2H, d, J = 8.2 Hz), 7.24 (2H, d, J = 8.2 Hz), 7.37 (1H, dd, J = 9.6,
10.2 Hz), 7.59 (1H, dd, J = 9.6, 9.6 Hz), 7.67 (1H, dd, J = 9.6, 10.0 Hz), 8.01 (1H, d, J = 10.0 Hz), 9.64
(1H, d, J = 10.0 Hz). Anal. Calcd for C24H20N2O4: C 71.99, H 5.03, N 7.00. Found: C 71.86, H 5.26, N
7.14.
2-Amino-3-cyano-4-(4-chlorophenyl)-10-ethoxycarbonylazuleno[2,1-b]pyran (3d): Deep red prism
(from EtOH). mp 206-208 ºC; IR (KBr, cm-1): ν 332 1 (NH2), 2219 (CN), 1642 (C=O). 1H-NMR (CDCl3):
δ 1.25 (3H, t, J = 7.2 Hz, OCH2CH3), 4.59 (2H, q, J = 7.2 Hz, CO2CH2CH3), 4.96 (2H, s, NH2), 5.26 (1H,
s, CH), 7.24 (2H, d, J = 8.2 Hz), 7.35 (2H, d, J = 8.2 Hz), 7.43 (1H, dd, J = 9.6, 10.2 Hz), 7.63 (1H, dd, J
= 9.6, 10.0 Hz), 7.78 (1H, dd, J = 9.6, 9.6 Hz), 7.94 (1H, d, J = 10.0 Hz), 9.65 (1H, d, J = 10.0 Hz). Anal.
Calcd for C23H17ClN2O3: C 68.23, H 4.23, N 6.92. Found: C 68.36, H 4.41, N 7.14.

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HETEROCYCLES, Vol. 85, No. 2, 2012
2-Amino-3-cyano-4-(4-fulorophenyl)-10-ethoxycarbonylazuleno[2,1-b]pyran (3e): Deep red prism
(from EtOH). mp 212-214 ºC; IR (KBr, cm-1): ν 3325 (NH2), 2206 (CN), 1648 (C=O). 1H-NMR (CDCl3:
δ 1.27 (3H, t, J = 7.2 Hz, OCH2CH3), 4.59 (2H, q, J = 7.2 Hz, CO2CH2CH3), 4.91 (2H, s, NH2), 5.27 (1H,
s, CH), 7.26 (2H, d, J = 8.8 Hz), 7.39 (2H, d, J = 8.8 Hz), 7.45 (1H, dd, J = 9.6, 10.2 Hz), 7.52 (1H, dd, J
= 9.6, 9.6 Hz), 7.69 (1H, dd, J = 9.6, 10.0 Hz), 8.12 (1H, d, J = 10.0 Hz), 9.66 (1H, d, J = 10.0 Hz). Anal.
Calcd for C23H17FN2O3: C 71.13, H 4.41, N 7.21. Found: C 71.26, H 4.58, N 7.39.
2-Amino-3-cyano-4-(4-hydroxyphenyl)-10-ethoxycarbonylazuleno[2,1-b]pyran (3f): Deep red prism
(from EtOH). mp 221-222 ºC; IR (KBr, cm-1): ν 3334 (NH2), 3225 (OH), 2208 (CN), 1640 (C=O).
1H-NMR (DMSO): δ 1.40 (3H, t, J = 7.2 Hz, OCH2CH3), 4.35 (2H, q, J = 7.2 Hz, CO2CH2CH3), 5.10 (1H,
s, CH), 6.62 (2H, d, J = 8.4 Hz), 6.95 (2H, s, NH2), 6.96 (2H, d, J = 8.4 Hz), 7.44 (1H, dd, J = 9.6, 10.0
Hz), 7.64 (1H, dd, J = 10.0, 10.0 Hz), 7.77 (1H, dd, J = 9.6, 9.6 Hz), 8.03 (1H, d, J = 9.6 Hz), 9.25 (1H, s,
OH), 9.38 (1H, d, J = 10.0 Hz). Anal. Calcd for C23H18N2O4: C 71.49, H 4.70, N 7.25. Found: C 71.63, H
4.84, N 7.36.
2-Amino-3-cyano-4-(4-methoxyphenyl)-10-ethoxycarbonylazuleno[2,1-b]pyran (3g): Deep red prism
(from EtOH). mp 214-216 ºC; IR (KBr, cm-1): ν 3342 (NH2), 2209 (CN), 1642 (C=O). 1H-NMR (CDCl3):
δ 1.27 (3H, t, J = 7.2 Hz, OCH2CH3), 3.94 (3H, s, OCH3), 4.50 (2H, q, J = 7.2 Hz, CO2CH2CH3), 4.84
(2H, s, NH2), 5.31 (1H, s, CH), 6.84-6.86 (2H, m), 7.07-7.09 (1H, m), 7.16 (1H, dd, J = 8.0, 8.0 Hz), 7.30
(1H, dd, J = 9.6, 9.6 Hz), 7.52 (1H, dd, J = 9.6, 10.0 Hz), 7.62 (1H, d, J = 9.6, 10.0 Hz), 8.01 (1H, d, J =
10.0 Hz), 9.48 (1H, d, J = 10.0 Hz). Anal. Calcd for C24H20N2O4: C 71.99, H 5.03, N 7.00. Found: C
72.13, H 5.15, N 7.21.
2-Amino-3-cyano-4-(4-hydroxyphenyl)-10-ethoxycarbonylazuleno[2,1-b]pyran (3h): Deep red prism
(from EtOH). mp 206-207 ºC; IR (KBr, cm-1): ν 3334 (NH2), 3241 (OH), 2218 (CN), 1645 (C=O).
1H-NMR (DMSO): δ 1.36 (3H, t, J = 7.2 Hz, OCH2CH3), 4.40 (2H, q, J = 7.2 Hz, CO2CH2CH3), 5.54 (1H,
s, CH), 6.78 (1H, d, J = 8.0 Hz), 6.81 (2H, s, NH2), 6.92 (1H, dd, J = 7.2, 7.2 Hz), 7.01 (1H, d, J = 8.0
Hz), 7.18 (1H, dd, J = 7.2, 7.2 Hz), 7.48 (1H, dd, J = 9.6, 9.6 Hz), 7.51~7.63 (2H, m), 8.63 (1H, d, J =
10.0 Hz), 9.01 (1H, d, J = 9.6 Hz), 10.51 (1H, s, OH). Anal. Calcd for C23H18N2O4: C 71.49, H 4.70, N
7.25. Found: C 71.72, H 4.86, N 7.42.
2-Amino-3-cyano-4-(2,4-dimethoxyphenyl)-10-ethoxycarbonylazuleno[2,1-b]pyran (3i): Deep red
1
prism (from EtOH). mp 189-190 ºC; IR (KBr, cm-1): ν 3334 (NH2), 2208 (CN), 1649 (C=O). H-NMR
(CDCl3, 400MHz) δ (ppm): 1.26 (3H, t, J = 7.2 Hz, OCH2CH3), 3.76 (3H, s, OCH3), 3.91 (3H, s, OCH3),
4.50 (2H, q, J = 7.2 Hz, CO2CH2CH3), 4.71 (2H, s, NH2), 5.63 (1H, s, CH), 6.32 (1H, d, J = 8.4 Hz), 6.50
(1H, s), 6.82 (1H, d, J = 8.4 Hz), 7.32 (1H, dd, J = 9.6, 9.6 Hz), 7.54 (1H, dd, J = 9.6, 10.0 Hz), 7.66 (1H,

HETEROCYCLES, Vol. 85, No. 2, 2012
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dd, J = 9.6, 9.6 Hz), 7.98 (1H, d, J = 10.0 Hz), 9.52 (1H, d, J = 10.0 Hz). Anal. Calcd for C25H22N2O5: C
69.76, H 5.15, N 6.51. Found: C 69.84, H 5.28, N 6.71.
2-Amino-3-cyano-4-(3,4-dimethoxyphenyl)-10-ethoxycarbonylazuleno[2,1-b]pyran (3j): Deep red
1
prism (from EtOH). mp 209-210 ºC; IR (KBr, cm-1): ν 3334 (NH2), 2208 (CN), 1649 (C=O). H-NMR
(DMSO): δ 1.40 (3H, t, J = 7.2 Hz, OCH2CH3), 3.66 (6H, s, 2xOCH3), 4.35 (2H, q, J = 7.2 Hz,
CO2CH2CH3), 5.17 (1H, s, CH), 6.63 (1H, d, J = 8.0 Hz), 6.80~6.85 (2H, m), 6.98 (2H, s, NH2), 7.46 (1H,
dd, J = 9.6, 9.6 Hz), 7.65 (1H, dd, J = 9.6, 10.0 Hz), 7.77 (1H, dd, J = 10.0, 10.0 Hz), 8.08 (1H, d, J =
10.0 Hz), 9.39 (1H, d, J = 10.0 Hz). Anal. Calcd for C25H22N2O5: C 69.76, H 5.15, N 6.51. Found: C
69.87, H 5.23, N 6.63.
2-Amino-3-cyano-4-(4-hydroxy-3-methoxyphenyl)-10-ethoxycarbonylazuleno[2,1-b]pyran
(3k):
Deep red prism (from EtOH). mp 213-215 ºC; IR (KBr, cm-1): ν 3334 (NH2), 3261 (OH), 2208 (CN),
1649 (C=O). 1H-NMR (DMSO): δ 1.40 (3H, t, J = 7.2 Hz, OCH2CH3), 3.67 (3H, s, OCH3), 4.36 (2H, q, J
= 7.2 Hz, CO2CH2CH3), 5.11 (1H, s, CH), 6.49 (1H, d, J = 8.0 Hz), 6.64 (1H, d, J = 8.0 Hz), 6.82 (1H, s),
6.96 (2H, s, NH2), 7.44 (1H, dd, J = 9.6, 10.0 Hz), 7.63 (1H, dd, J = 10.0, 10.0 Hz), 7.74 (1H, dd, J = 10.0,
10.0 Hz), 8.07 (1H, d, J = 10.0 Hz), 8.84 (1H, s, OH), 9.37 (1H, d, J = 10.0 Hz). Anal. Calcd for
C24H20N2O5: C 69.22, H 4.84, N 6.73. Found: C 69.37, H 4.96, N 6.79.
2-Amino-3-cyano-4-(3-nitrophenyl)-10-ethoxycarbonoxyazuleno[2,1-b]pyran (3l): Deep red prism
1
(from MeOH). mp 209-210 ºC; IR (KBr, cm-1): ν 3339 (NH2), 2212 (CN), 1656 (C=O). H-NMR
(DMSO): δ 1.41 (3H, t, J = 7.2 Hz, OCH2CH3), 4.36 (2H, q, J = 7.2 Hz, CO2CH2CH3), 5.51 (1H, s, CH),
7.20 (2H, s, NH2), 6.50 (1H, dd, J = 9.6, 9.6 Hz), 7.56 (1H, dd, J = 8.0, 8.2 Hz), 7.64 (1H, d, J = 8.4 Hz),
7.68 (1H, d, J = 9.6 Hz), 7.77 (1H, dd, J = 9.6, 9.6 Hz), 8.04~8.07 (2H, m), 8.09 (1H, d, J = 9.6 Hz), 9.42
(1H, d, J = 10.0 Hz). Anal. Calcd for C23H17N3O5: C 66.50, H 4.12, N 10.12. Found: C 66.64, H 4.33, N
10.26.
2-Amino-3-cyano-4-(2-thienyl)-10-ethoxycarbonylazuleno[2,1-b]pyran (3m): Deep red prism (from
1
MeOH). mp 208-210 ºC; IR (KBr, cm-1): ν 3328 (NH2), 2217 (CN), 1657 (C=O). H-NMR (DMSO): δ
1.40 (3H, t, J = 7.2 Hz, OCH2CH3), 4.35 (2H, q, J = 7.2 Hz, CO2CH2CH3), 5.63 (1H, s, CH), 6.90 (1H, d,
J = 3.2 Hz), 7.12 (2H, s, NH2), 7.13~7.15 (2H, m), 7.28 (1H, d, J = 4.4 Hz), 7.51 (1H, dd, J = 9.6, 9.6 Hz),
7.66 (1H, dd, J = 9.6, 10.0 Hz), 7.81 (1H, dd, J = 9.6, 9.6 Hz), 8.22 (1H, d, J = 9.6 Hz), 9.39 (1H, d, J =
10.0 Hz). Anal. Calcd for C21H16N2O3S: C 67.00, H 4.28, N 7.44. Found: C 67.24, H 4.36, N 7.61.
2-Amino-3-cyano-4-(2-furyl)-10-ethoxycarbonylazuleno[2,1-b]pyran (3n): Deep red prism (from
1
MeOH). mp 187-189 ºC; IR (KBr, cm-1): ν 3341 (NH2), 2213 (CN), 1652 (C=O). H-NMR (DMSO): δ
1.40 (3H, t, J = 7.2 Hz, OCH2CH3), 4.39 (2H, q, J = 7.2 Hz, CO2CH2CH3), 4.90 (2H, s, NH2), 5.38 (1H, s,

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CH), 6.19 (1H, d, J = 2.8 Hz), 6.30 (1H, dd, J = 1.8, 2.6 Hz), 7.30 (1H, d, J = 1.0 Hz), 7.47 (1H, dd, J =
9.6, 9.6 Hz), 7.62 (1H, dd, J = 9.6, 10.0 Hz), 7.76 (1H, dd, J = 9.6, 9.6 Hz), 8.24 (1H, d, J = 9.6 Hz), 9.39
(1H, d, J = 9.6 Hz). Anal. Calcd for C21H16N2O4: C 69.99, H 4.48, N 7.77. Found: C 69.87, H 4.61, N
7.65.
ACKNOWLEDGEMENT
We thank the Innovation Team Foundation of Liaoning Education Department (No. 2008T001).
REFERENCES
1. a) Y. Tang, J. Oppenheimer, Z. Song, L. You, X. Zhang, and R. P. Hsung, Tetrahedron, 2006, 62,
10785; b) E. J. Jung, B. H. Park, and Y. R. Lee, Green Chem., 2010, 12, 2003.
2. a) S. Kumar, D. Hernandez, B. Hoa, Y. Lee, J. S. Yang, and A. McCurdy, Org. Lett., 2008, 10, 3761;
b) M. Rawat, V. Prutyanov, and W. D. Wulff, J. Am. Chem. Soc., 2006, 128, 11044.
3. J. M. Quintela, C. P. Einador, and M. J. Moreira, Tetrahedron, 1995, 51, 5901.
4. S. Srivastava, S. Batra, and A. P. Bhaduri, Indian J. Chem., Sect. B., 1996, 35B, 602.
5. V. Santagada, E. Perissutti, and G. Liendo, Curr. Med. Chem., 2002, 9, 1251.
6. T. Yanagisawa, S. Wakabayashi, T. Tomiyama, M. Yasunami, and K. Takase, Chem. Pharm. Bull.,
1988, 36, 641.
7. a) A. E. Asato, A. Peng, M. Z. Hossain, T. Mirzadegan, and J. Bertram, J. Med. Chem., 1993, 36,
3137; b) B. C. Hong, Y.-F. Jiang, and E. S. Kumar, Bioorg. Med. Chem. Lett., 2001, 11, 1981.
8. D. A. Becker, J. J. Ley, L. Echegoyen, and R. Alvarado, J. Am. Chem. Soc., 2002, 124, 4678.
9. a) T. Morita, T. Nakadate, and K. Takase, Heterocycles, 1981, 15, 835; b) K. Fujimori, T. Fujita, K.
Yamane, M. Yasunami, and K. Takase, Chem. Lett., 1983, 12, 1721; c) K. Yamane, K. Fujimori, S.
Ichikawa, S. Miyoshi, and K. Hashizume, Heterocycles, 1983, 20, 1263; d) K. Fujimori, H. Fukazawa,
Y. Nezu, K. Yamane, M. Yasunami, and K. Takase, Chem. Lett., 1986, 15, 1021.
10. a) D. L. Wang, S. Kikuchi, and K. Imafuku, J. Heterocycl. Chem., 2004, 41, 723; b) D. L. Wang, J.
Xu, and Z. Gu, Chin. J. Org. Chem., 2007, 27, 1404; c) J. Xu, D. L. Wang, and K. Imafuku, Synth.
Commun., 2009, 39, 2196; d) D. L. Wang, S. F. Li, W. Li, Y. F. Li, and L. N. Lin, Chin. Chem. Lett.,
2011, 22, 789.
11. T. Nozoe, K. Takase, and N. Shimazaki, Bull. Chem. Sos. Jap., 1964, 37, 1644.