A novel method for one-pot synthesis of furo[3,2-c]coumarin derivatives from 4-hydroxycoumarin and arylglyoxal under microwave irradiation

Article abstract of DOI:10.1002/cjoc.201200157

A novel one-pot synthesis of furo[3,2-c]coumarins has been developed from readily available starting materials 4-hydroxycoumarin and arylglyoxal. This method is simple, rapid and good yielding.

Full text of DOI:10.1002/cjoc.201200157

FULL PAPER
DOI: 10.1002/cjoc.201200157
A Novel Method for One-pot Synthesis of Furo[3,2-c]coumarin
Derivatives from 4-Hydroxycoumarin and Arylglyoxal under
Microwave Irradiation
Chen, Zhiwei(陈志卫)
Bi, Jianhao(毕建豪)
Su, Weike*(苏为科)
Key Laboratory for Green Pharmaceutical Technologies and Related Equipment of Ministry of Education, College
of Pharmaceutical Sciences, Zhejiang University of Technology, Hangzhou, Zhejiang 310014, China
A novel one-pot synthesis of furo[3,2-c]coumarins has been developed from readily available starting materials
4-hydroxycoumarin and arylglyoxal. This method is simple, rapid and good yielding.
Keywords furocoumarins, 4-hydroxycoumarin, arylglyoxal, microwave irradiation, one-pot synthesis
Introduction
oxal 2a (Scheme 1).
Furocoumarins are widely present in numerous
natural products, manifest a wide range of biological
activities, such as antibacterial, anti-HIV, insecticides,
antioxidants, antitumor and antiviral properties, and
they are also widely applied in the pharmaceutical in-
dustry.[1] Synthesis and screening of furocoumarins
compounds for drug discovery has been a vital subject
of constant interest in organic and medicinal chemistry.
To date, synthetic methodologies for the synthesis of
furocoumarins have been studied for many years.[2]
Recently, Cheng[3] and coworkers have prepared
Scheme 1
O
OH
O
Cl
OH
O
O
O
O
3a
TM
O
O
O
H
3-chloro-4H-furo[3.2-c]chromen
derivatives
from
+
3-alkynylchromone via one-pot reaction. Also, Xu[4]
have prepared furo[3,2-c]chromen via coupling cycliza-
tion strategy with 3-bromo-4-acetoxycoumarins and
1-alkynes catalyzed by palladium/copper. These meth-
ods have their own merits in the preparation of the indi-
vidual target compounds, however, these methods usu-
ally require rather specific substrates (e.g., 3-alkynyl-
chromone), most of which are commercially unavailable,
long reaction time (20 h), heavy metal (CuCl2, CuBr,
CuCl, Pd) used. Therefore, there is an eager desire to
explore a simple and very effective method for prepara-
tion of a wide variety of the furocoumarins.
O
OH
1a
2a
Results and Discussion
In the study of the condensation of 4-hydroxycou-
marin with phenylglyoxal, it was found that generally
two molecules of 4-hydroxycoumarin (1a) react with
one of the phenylglyoxal (2a) to obtain the Michael ad-
ducts (4a) as the final product.[6] Herein, we hope to
obtain the product 3a from the reaction of 4-hydroxy-
coumarin 1a with phenylglyoxal 2a. As show in Table 1,
no product 3a was observed but 4a was obtained in high
yield when the reaction was kept in EtOH reflux for 2 h
in the absence of catalyst. Disappointedly, the product
3a was also not obtained when this reaction was heated
at reflux in EtOH for 60 min in the presence of catalyst
PTSA or DBU (Table 1, Entries 2—3). When 20 mol%
DABCO, [dabco][HCOO]2 and [dabco][CH3COO]2
As part of our continuing efforts on the development
of new route for the synthesis of novel coumarin deriva-
tives,[5] herein we report a novel and efficient route to
one-pot syntheses of 3-chloro-4H-furo[3,2-c]chromen
derivatives from readily available reagents. A retrosyn-
thetic analysis suggested the formation of the furan ring
via ring closure of 3a, which results from the condensa-
tion reaction of 4-hydroxycoumarin 1a and phenylgly-
*
E-mail: pharmlab@zjut.edu.cn; Tel.: 0086-0571-88320752; Fax: 0086-0571-88320752
Received February 19, 2012; accepted March 27, 2012; published online XXXX, 2012.
Supporting information for this article is available on the WWW under http://dx.doi.org/10.1002/cjoc.201200157 or from the author.
Chin. J. Chem. 2012, XX, 1—6
© 2012 SIOC, CAS, Shanghai, & WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
1

Chen, Bi & Su
FULL PAPER
Table 1 Synthesis of product 3a under different conditionsa
O
OO
O
O
O
OH
O
O
+
H
OH
OH
OH
+
O
O
O
O
OH
4a
2a
1a
3a
Yieldb/%
3a 4a
Entry Catalyst
Loading/mol%
Solvent
Temperature
Time/min
1
none
—
EtOH
EtOH
EtOH
EtOH
EtOH
EtOH
EtOH
EtOH
EtOH
EtOH
EtOH
reflux
reflux
reflux
r.t.
120
60
60
28
25
26
19
25
11
28
15
16
13
19
trace 52
trace 63
trace 88
2
PTSA
20
3
DBU
20
4
DABCO
20
21
24
27
45
76
96
92
96
95
94
96
63
5
[dabco][HCOO]2
[dabco[CH3COO]2
[dabco[CH3COO]2
[dabco[CH3COO]2
[dabco[CH3COO]2
DABCO
20
r.t.
61
6
20
r.t.
57
7
50
r.t.
41
8
100
150
150
250
150
150
150
r.t.
9
9
r.t.
trace
trace
trace
trace
trace
trace
10
11
12
13
14
r.t.
[dabco][CH3COO]2
[dabco][CH3COO]2
[dabco][CH3COO]2
[dabco][CH3COO]2
r.t.
ClCH2CH2Cl
CH2Cl2
r.t.
r.t.
CH3CN
r.t.
15
[dabco][CH3COO]2
150
THF
r.t.
18
92
trace
a All reactions were run with the molar ratio of 1a∶2a＝1∶1. b Isolated yield of 3a based on 1a.
were undertaken, it should be mentioned that besides 3a,
a noticeable amount of 4a was also obtained (Table 1,
Entries 4—6). To our surprise, when the loading amount
of catalyst increased, the yield was improved (Table 1,
Entries 7 — 11). It was found that 150 mol%
[dabco][CH3COO]2 was enough to promote the reaction
efficiently for preparing 3a (Table 1, Entry 9). Next,
different solvents were also tested in the presence of
[dabco][CH3COO]2 as catalyst, for example, EtOH,
THF, ClCH2CH2Cl, CH2Cl2 and CH3CN, to our delight,
they also resulted in high yields (Table 1, Entries 9, 12
—15).
tautomerism affords the corresponding product 4a.
With the aim to obtain the product 5a, POCl3 was
used, the results were summarized in Table 2. It was
found that 3a was treated with 2.0 equiv. of POCl3 in
CH2ClCH2Cl at room temperature for 8 h, the desired
product 5a was obtained in 35% (Table 2, Entry 2). In-
creasing the reaction temperature, the yield was im-
proved obviously. When the reaction of 3a with 2.0
equiv. of POCl3 was performed in reflux condition for 2
h, the yield of 5a reached to 65% (Table 2, Entry 4).
Organic reactions accelerated by microwave irradia-
tion has attracted considerable attention over the past
number of years for the efficient synthesis of a variety
of organic compounds.[9] Microwave-assisted reactions
are particularly effective when small polar molecules are
part of the reaction transformation.[10-12] With the aim to
reduce reaction time and improve the yield, microwave
heating was employed. After optimization of the reac-
tion conditions, the reaction was generally completed in
the presence of POCl3 at 130 ℃ in CH2ClCH2Cl for 15
min under microwave irradiation of 3a. Finally, the
two-step sequence can be carried out in a one-pot man-
ner without the isolation of the product 3a, the reaction
would be greatly improved and the yield was increased
from 65% to 81%.
It is well-known that acids[7] (such as HClO4, BF3•
Et2O) and dehydrating agent[8] (such as POCl3, P2O5)
were employed for the Paal-Knorr furan synthesis. The
close loop of the 3a was chosen as a model reaction to
optimize the reactions. It was found that when PTSA,
HClO4, Yb(OTf)3, CF3COOH, BF3•Et2O were used as
catalysts, the expected product of 3-OH-4H-furo[3.2-
c]chromen 6a was not gotten, but much amount of by-
product 4a was obtained. A plausible mechanism for
this reaction is proposed in Scheme 2. The product 3a is
not stable, first 3a loses H2O to afford II, next another
molecule of 4-hydroxycoumarin is added to
α,β-unsaturated carbonyl intermediate II to form III via
1,4-conjugate addition. Then, the subsequent keto-enol
2
www.cjc.wiley-vch.de
© 2012 SIOC, CAS, Shanghai, & WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
Chin. J. Chem. 2012, XX, 1—6

A Novel Method for One-pot Synthesis of Furo[3,2-c]coumarin Derivatives
Scheme 2
O
Cl
O
O
O
O
OH
POCl3
H
+
OH
O
O
O
OH
5a
O
O
2a
1a
3a
O
OH
- H2O
O
O
O
OO
O
O
OO
O
O
O
O
1a
- H2O
H
OH
O
OH
OH
O
O
O
Ⅱ
Ⅲ
4a
capillary melting point apparatus and uncorrected. IR
spectra was recorded on an AVATAR-370, samples
Table 2 Synthesis of 5a under different conditions
Yielda/%
5a 4a
trace 13
1
were prepared as KBr plates. H NMR and 13C NMR
Loading/
mol%
Entry Reagent
Condition
spectra were recorded at VARAIN-400 using DMSO or
CDCl3 as the solvent with tetramethylsilane (TMS) as
an internal standard. Chemical shifts (δ) are given rela-
tive to TMS, the coupling constants J are given in Hz.
Mass spectra were measured with Thermo Finnigan
LCQ-Advantage. High resolution mass spectral (HRMS)
analyses were measured on an Agilent 6210 TOF
LC/MS using ESI or EI (electrospray ionization) tech-
niques.
1
POCl3 100
POCl3 200
ClCH2CH2Cl, r.t., 8 h
ClCH2CH2Cl, r.t., 8 h
r.t., 8 h
2
35
37
65
9
7
4
3
POCl3 200
POCl3 200
POCl3 200
POCl3 200
POCl3 200
POCl3 300
4
ClCH2CH2Cl, reflux, 2 h
5b
6b
7b
8b
ClCH2CH2Cl, 110 ℃, 20 min 72 trace
ClCH2CH2Cl, 120 ℃, 18 min 74 trace
ClCH2CH2Cl, 130 ℃, 15 min 79 trace
ClCH2CH2Cl, 130 ℃, 15 min 78 trace
General procedure for the preparation of [dabco]-
[CH3COO]2
a Isolated yields based on 3a. b Under microwave heating.
To a solution of dabco (10 mmol) in EtOH (3 mL)
was added CH3COOH (20.2 mmol) in portion within 30
min, and then the mixture was stirred at room for 1 h
and evaporated under reduced pressure to give [dabco]-
After optimizing the reaction conditions, the scope of
this method was evaluated using coumarins 1a—1c, and
phenylglyoxals 2a — 2h, and the corresponding
3-chloro-4H-furo[3.2-c]chromen compounds 5a — 5k
were obtained in moderate to excellent yields, as sum-
marized in Table 3. The nature of R1 group on the
4-hydroxycoumarin 1a showed no significant effect on
the yield, electron-withdrawing group substituted com-
pounds showed slightly higher yields than electron-do-
nating group on arylglyoxals. But, this reaction was car-
ried out with glyoxals such as 2-furanylglyoxal and
ethylglyoxal, the TLC and 1H-NMR spectra of the crude
reaction mixture showed the presence of a combination
of starting materials and numerous by-products, and the
yield of the expected product was very poor.
1
[CH3COO]2 as a white solid; m.p. 69.5—73.2 ℃; H
NMR (400 MHz, CDCl3) δ: 2.90 (s, 12H), 1.94 (s, 3H);
13C NMR (100 MHz, CDCl3) δ: 175.6, 45.2, 22.3. MS
(ESI) m/z: 113 [M－(CH3COOH)2]＋.
General procedure for the synthesis of 3a
To a mixture of 4-hydroxycoumarin 1a (1 mmol),
phenylglyoxal 2a (1 mmol) was added [dabco]-
[CH3COO]2 (1.5 mmol) in EtOH (2 mL), and the reac-
tion mixture was stirred at room temperature and moni-
tored by TLC [V(CH2Cl)∶V(CH3OH)＝10∶1). After
completion of the reaction, compounds were purified by
column chromatography on silica to give the corre-
sponding compound 3a.
Experimental
4-Hydroxy-3-(1-hydroxy-2-oxo-2-phenylethyl)-2H-
chromen-2-one (3a) White solid; m.p. ＞300 ℃; H
NMR (400 MHz, DMSO) δ: 7.98—7.96 (m, 2H), 7.77
All microwave irradiation experiments were carried
out in a Discover-CEM monomode microwave appara-
tus. Melting points were determined on a Büchi B-540
1
Chin. J. Chem. 2012, XX, 1—6
© 2012 SIOC, CAS, Shanghai, & WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
www.cjc.wiley-vch.de
3

Chen, Bi & Su
FULL PAPER
Table 3 One-pot, two-step synthesis of 3-chloro-4H-furo[3.2-c]chromen derivatives
R2
O
(1) [dabco][CH3COO]2 (1.5 equiv.)
1,2-dichloroethane, r.t.,16 min
O
O
H
R2
O
+
R1
R1
O
Cl
(2) POCl3, MW, 130 oC, 15 min
OH
2a
2h
1a 1c
O
O
5a
5k
Entry
R1
H (1a)
H
R2
H (2a)
Product
5a
Yielda/%
81
1
2
4-F (2b)
5b
5c
84
3
H
4-Cl (2c)
4-Br (2d)
4-Me (2e)
83
4
H
5d
5e
82
5
H
79
6
H
4-MeO (2f)
3-Cl (2g)
3-MeO (2h)
H
5f
78
7
H
5g
82
8
H
5h
5i
74
9
Me (1b)
Me
80
10
11
3-Cl
5j
83
t-Bu (1c)
H
5k
82
a Isolated yields based on 1a—1c.
－
＋
1
(dd, J＝1.6, 8.0 Hz, 1H), 7.48—7.44 (m, 1H), 7.37—
7.31 (m, 3H), 7.08—7.00 (m, 2H), 6.08 (s, 1H); 13C
NMR (100 MHz, DMSO) δ: 197.7, 172.8, 163.3, 153.5,
135.5, 132.2, 130.2, 127.8, 127.29, 124.6, 122.4, 121.7,
115.5, 93.4, 78.2; IR (KBr) ν: 1671, 1638, 1600, 1522,
1449, 1419, 1353, 1061 cm ; MS (ESI) m/z: 295 (M－
H) － . HRMS calcd for C17H13O5 297.0763, found
297.0763.
1029 cm ; MS (EI) m/z: 296 (M , 100). HRMS calcd
for C17H9ClO3 296.0240, found 296.0245.
3-Chloro-2-(4-fluorophenyl)-4H-furo[3,2-c]-
chromen-4-one (5b) White solid, m.p. 171—173 ℃;
1H NMR (400 MHz, CDCl3) δ: 8.03 (dd, J＝5.6, 8.0 Hz,
2H), 7.90 (d, J＝8.0 Hz, 1H), 7.57—7.53 (m, 1H ), 7.44
—7.36 (m, 2H), 7.22—7.17 (m, 2H); 13C NMR (100
MHz, CDCl3) δ: 164.5, 162.0, 155.8, 155.6, 152.9,
149.4, 131.4, 128.1, 128.0, 124.7, 124.4, 120.8, 117.5,
116.3, 116.0, 112.4, 110.4, 110.3; IR (KBr) ν: 2925,
－
1
Typical procedure for the one-pot synthesis of 5a
－
1
In a 10 mL pressurized vial “snap-on” cap, a mixture
of 4-hydroxycoumarin 1a (1 mmol), and phenylglyoxal
2a (1 mmol) was added [dabco][CH3COO]2 (1.5 mmol)
in ClCH2CH2Cl (4 mL). The reaction mixture was
stirred at room temperature and monitored by TLC. Af-
ter completion of the first reaction, 0.3 g POCl3 (2.0
mmol) was added and the reaction mixture was irradi-
ated for 15 min at 130 ℃, the reaction mixture was then
allowed to cool to room temperature and poured into
crushed ice (10 mL), the aqueous phase was extracted
with CH2Cl2 (10 mL×3), the combined organic extracts
were washed with brine (10 mL) and then dried over
Na2SO4, filtered, compounds were then purified by
column chromatography on silica to give the corre-
sponding compound. Other products (5b—5k) were
prepared according to the same method of 5a.
1754, 1632, 1496, 1408, 1167, 1095 cm ; MS (EI) m/z:
314 (M＋, 100). HRMS calcd for C17H8ClFO3 314.0146,
found 314.0131.
3-Chloro-2-(4-chlorophenyl)-4H-furo[3,2-c]-
chromen-4-one (5c) White solid, m.p. 169—170 ℃;
1H NMR (400 MHz, CDCl3) δ: 7.99 (d, J＝8.0 Hz, 2H),
7.92 (d, J＝8.0 Hz, 1H ), 7.59—7.37 (m, 5H ); 13C
NMR (100 MHz, CDCl3) δ: 155.9, 155.5, 152.5, 148.7,
135.2, 131.4, 129.0, 126.8, 125.1, 124.7, 120.7, 117.4,
111.9, 110.7, 100.1; IR (KBr) ν: 2923, 1746, 1629, 1486,
－
＋
1
1402, 1098, 1033 cm ; MS (EI) m/z: 330 (M , 100).
HRMS calcd for C17H8Cl2O3 329.9850, found 329.9846.
2-(4-Bromophenyl)-3-chloro-4H-furo[3,2-c]-
chromen-4-one (5d) White solid, m.p. 239—241 ℃;
1H NMR (400 MHz, CDCl3) δ: 7.93 (d, J＝8.4 Hz, 3H),
7.63 (d, J＝8.8 Hz, 2H), 7.59—7.55 (m, 1H), 7.46—
7.37 (m, 2H); 13C NMR (100 MHz, CDCl3) δ: 155.7,
152.8, 149.0, 132.1, 131.5, 127.2, 126.8, 124.8, 123.7,
120.9, 117.5, 112.2, 111.1, 110.4; IR (KBr) ν: 2924,
3-Chloro-2-phenyl-4H-furo[3,2-c]chromen-4-one
1
(5a) White solid, m.p. 163—165 ℃; H NMR (400
MHz, CDCl3) δ: 8.04 (d, J＝7.6 Hz, 1H), 7.92 (d, J＝
8.0 Hz, 1H), 7.56—7.35 (m, 6H); 13C NMR (100 MHz,
CDCl3) δ: 156.2, 155.4, 152.5, 149.8, 131.3, 129.4,
128.8, 127.7, 125.7, 124.7, 120.8, 117.4, 112.1, 110.2,
110.2; IR (KBr) ν: 1757, 1633,1489, 1446, 1419, 1095,
－
1
1747, 1616, 1483, 1412, 1091, 1082 cm ; MS (EI) m/z:
376 (M＋, 100).
3-Chloro-2-p-tolyl-4H-furo[3,2-c]chromen-4-one
1
(5e) White solid, m.p. 169—170 ℃; H NMR (400
4
www.cjc.wiley-vch.de
© 2012 SIOC, CAS, Shanghai, & WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
Chin. J. Chem. 2012, XX, 1—6

A Novel Method for One-pot Synthesis of Furo[3,2-c]coumarin Derivatives
MHz, CDCl3) δ: 7.96—7.92 (m, 3H), 7.55 (t, J＝8.0 Hz,
9-tert-Butyl-3-chloro-2-(3-chlorophenyl)-4H-furo-
1H ), 7.45 (d, J＝8.0 Hz, 1H), 7.38 (t, J＝8.0 Hz, 1H),
7.31 (t, J＝8.4 Hz, 2H), 2.41 (s, 3H); 13C NMR (100
MHz, CDCl3) δ: 156.2, 155.0, 152.4, 149.9, 139.6,
131.1, 129.4, 125.4, 124.8, 124.6, 120.6, 117.2, 112.0,
110.0, 109.3, 21.4; IR (KBr) ν: 2920, 1747, 1631, 1495,
[3,2-c]chromen-4-one (5k) White solid, m.p. 218—
220 ℃; 1H NMR (400 MHz, CDCl3) δ: 8.09 (d, J＝8.0
Hz, 2H), 7.89 (d, J＝4.0 Hz, 1H), 7.61 (dd, J＝4.0, 8.0
Hz, 1H), 7.53 (t, J＝8.0 Hz, 2H), 7.42 (dd, J＝8.0, 24.0
Hz, 2H), 1.42 (s, 9H); 13C NMR (100 MHz, CDCl3) δ:
156.4, 155.9, 150.7, 149.6, 148.0, 129.3, 129.0, 128.7,
127.9, 125.8, 117.0, 111.6, 110.3, 110.0, 77.4, 77.1,
76.8, 35.0, 31.6; IR (KBr) ν: 2962, 1749, 1635, 1568,
－
＋
1
1454, 1360, 1095, 1028 cm ; MS (EI) m/z: 310 (M ,
100).
3-Chloro-2-(4-methoxyphenyl)-4H-furo[3,2-c]-
chromen-4-one (5f) White solid, m.p. 182—184 ℃;
1H NMR (400 MHz, CDCl3) δ: 8.00 (d, J＝8.0 Hz, 2H),
7.92 (d, J＝8.0 Hz, 1H), 7.54 (t, J＝4.0 Hz, 1H), 7.56—
7.36 (m, 2H), 7.03 (d, J＝8.0 Hz, 2H), 3.89 (s, 3H); 13C
NMR (100 MHz, CDCl3) δ: 160.4, 156.3, 155.0, 152.6,
150.2, 131.1, 130.8, 127.5, 124.7, 120.7, 120.6, 117.4,
114.4, 112.4, 110.3, 55.6; IR (KBr) ν: 2923, 1750, 1607,
－
＋
1
1487, 1258, 1123, 1003 cm ; MS (EI) m/z: 352 (M ,
65). HRMS calcd for C21H17ClO3 352.0866, found
352.0858.
3,3'-(2-Oxo-2-phenylethane-1,1-diyl)bis(4-hydroxy-
2H-chromen-2-one) (4a) White solid, m.p. 200—203
1
℃; H NMR (400 MHz, CDCl3) δ: 11.23 (s, 2H, OH),
8.06 (dd, J＝1.6, 8 Hz, 2H), 7.83—7.81 (m, 2H), 7.62—
7.58 (m, 2H), 7.49—7.45 (m, 1H), 7.40—7.32 (m, 6H),
6.09 (s, 1H); MS (ESI) m/z: 439(M－H)－.
－
＋
1
1498, 1305, 1259, 1189 cm ; MS (EI) m/z: 326 (M ,
100).
3-Chloro-2-(3-chlorophenyl)-4H-furo[3,2-c]-
chromen-4-one (5g) White solid, m.p. 198—200 ℃;
1H NMR (400 MHz, CDCl3) δ: 8.00 (s, 1H), 7.95 (t,
J＝8.0 Hz, 2H), 7.57 (t, J＝8.0 Hz, 1H), 7.45—7.38 (m,
4H); 13C NMR (100 MHz, CDCl3) δ: 155.7, 155.60,
152.5, 148.0, 134.7, 131.5, 130.0, 129.1, 125.2, 124.7,
123.4, 120.7, 117.3, 111.7, 111.3, 110.0; IR (KBr) ν:
2924, 1755, 1632, 1570, 1476, 1400, 1278, 1003 cm ;
MS (EI) m/z: 330 (M ＋ , 100), HRMS calcd for
C17H8Cl2O3: 329.9850, found 329.9850.
Conclusions
In conclusion, an extremely efficient method has
been developed for the one-pot synthesis of 3-chloro-
4H-furo[3.2-c]chromen derivatives form 4-hydroxy-
coumarin derivatives and arylglyoxals. The methodol-
ogy is efficient, simple work-up, heavy metal catalyst-
free and using commercially available reagents. This
class of compounds may be used to construct some bio-
active compounds.
－
1
3-Chloro-2-(3-methoxyphenyl)-4H-furo[3,2-c]-
chromen-4-one (5h) White solid, m.p. 137—140 ℃;
1H NMR (400 MHz, CDCl3) δ: 7.96 (d, J＝8.0 Hz, 1H),
7.53—7.33 (m, 5H), 7.18 (s, 1H), 6.94 (s, 1H), 3.91 (s,
3H); 13C NMR (100 MHz, CDCl3) δ: 159.9, 158.1,
156.7, 156.3, 152.5, 130.6, 130.1, 128.8, 124.5, 120.8,
117.4, 117.1, 114.6, 112.7, 112.4, 110.1, 103.0, 55.5; IR
(KBr) ν: 2927, 1747, 1634, 1579, 1461, 1280, 1274,
Acknowledgement
We are grateful to the National Natural Science
Foundation of China (No. 20876147) for financial help.
References
－
＋
1
1237 cm ; MS (EI) m/z: 327 (M , 94).
[1] (a) Santana, L.; Uriarte, E.; Roleira, F.; Milhazes, N.; Borges, F.
Curr. Med. Chem. 2004, 11, 3239; (b) Wang, X. H.; Bastow, K. F.;
Sun, C. M.; Lin, Y. L.; Yu, H. J. J. Med. Chem. 2004, 47, 5816; (c)
Dong, Y. H.; Shi, Q.; Pai, H. C.; Peng, C. Y.; Pan, S. H.; Teng, C. M.
J. Med. Chem. 2010, 53, 2299.
[2] (a) Guillaume, R.; Marion, R.; Geneviève, B.; Nuno, M. Org. Lett.
2009, 22, 5254; (b) Elisa, A.; Massimiliano, C.; Giovanni, G.;
Francesco, R.; Angela, S. Tetrahedron 2010, 66, 9493; (c) Abdullah,
G. A.; Sameh, R. E. Chin. J. Chem. 2012, 30, 316.
3-Chloro-9-methyl-2-phenyl-4H-furo[3,2-c]-
chromen-4-one (5i) White solid, m.p. 181—183 ℃;
1H NMR (400 MHz, CDCl3) δ: 8.06 (dd, J＝1.2, 8.4 Hz,
1H), 7.70 (s, 1H), 7.53—7.49 (m, 2H), 7.45—7.41 (m,
2H), 7.36—7.30 (m, 2H), 2.48 (s, 3H); 13C NMR (100
MHz, CDCl3) δ: 156.1, 155.2, 150.7, 149.5, 134.7,
132.3, 129.3, 128.8, 127.8, 125.5, 120.3, 117.0, 111.7,
110.3, 110.0, 21.2; IR (KBr) ν: 2921, 1739, 1634, 1572,
[3] (a) Cheng, G.; Hu, Y. H. Chem. Commun. 2007, 3285; (b) Cheng, G.;
Hu, Y. H. J. Org. Chem. 2008, 73, 4732.
－
＋
1
1487, 1419, 1264, 1090 cm ; MS (EI) m/z: 310 (M ,
100). HRMS calcd for C18H11ClO3 310.0397, found
310.0389.
[4] Chen, L.; Li, Y.; Xu, M. H. Org. Biomol. Chem. 2010, 8, 3073.
[5] Chen, Z. W.; Zhu, Q.; Su, W. K. Tetrahedron Lett. 2011, 52, 2601.
[6] (a) Kolos, N. N.; Gozalishvili, L. L.; Sivokon, E. N.; Knyazeva, I. V.
Russ. J. Org. Chem. 2009, 45, 119; (b) Kolos, N. N.; Gozalishvili, L.
L.; Yaremenko, F. G.; Shishkin, O. V.; Shishkina, S. V.;
Konovalovac, I. S. Russ. Chem. Bull. 2007, 56, 2277.
[7] (a) Fajarıí, L.; Brillas, E.; Alemán, C.; Juliá, L. J. Org. Chem. 1998,
63, 5324; (b) Wu, A. X.; Wang, M. Y.; Gan, Y. H.; Pan, X. F. J.
Chem. Res. 1998, 30, 136; (c) Jones, R. A.; Civcir, P. U.
Tetrahedron 1997, 53, 11529; (d) Stauffer, F.; Neier, R. Org. Lett.
2000, 2, 3535; (e) Yin, G. D.; Wang, Z. H.; Chen, A. H.; Gao, M.;
Wu, A. X.; Pan, Y. J. J. Org. Chem. 2008, 73, 3377.
3-Chloro-2-(3-chlorophenyl)-9-methyl-4H-furo[3,
2-c]chromen-4-one (5j) White solid, m.p. 196—198
℃; 1H NMR (400 MHz, CDCl3) δ: 8.02 (s, 1H), 7.98 (d,
J＝8.0 Hz, 1H), 7,72 (s, 1H), 7.46—7.32 (m, 4H), 2.50
(s, 1H); 13C NMR (100 MHz, CDCl3) δ: 155.9, 155.5,
150.6, 147.7, 134.7, 134.7, 132.5, 129.9, 129.1, 129.0,
125.1, 123.3, 120.3, 116.9, 111.3, 109.8, 21.0; IR (KBr)
ν: 2922, 1764, 1638, 1573, 1474, 1401, 1086, 1002
－
＋
1
cm ; MS (EI) m/z: 344 (M , 100). HRMS calcd for
C18H10Cl2O3 344.0007, found 343.9997.
[8] (a) Venugopal, M.; Balasundaram, B.; Perumal, P. T. Synth.
Chin. J. Chem. 2012, XX, 1—6
© 2012 SIOC, CAS, Shanghai, & WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
www.cjc.wiley-vch.de
5

Chen, Bi & Su
FULL PAPER
Commun. 1993, 23, 2593; (b) Nicolaou, K. C.; Hao, J. L.; Reddy, M.
V. J. Am. Chem. Soc. 2004, 126, 12897.
2012, 30, 670; (e) Maher, A. E.; Ahmed, Y. E.; Mamdouh, A. T.;
Ibrahim, E. E. Chin. J. Chem. 2012, 30, 616.
[9] (a) Kappe, C. O. Angew. Chem., Int. Ed. Engl. 2004, 43, 6250; (b)
Lidström, P.; Tierney, J.; Wathey, B.; Westman, J. Tetrahedron
2001, 57, 9225; (c) Gabriel, C.; Gabriel, S.; Grant, E. H.; Halstead, B.
S. J.; Mingos, D. M. P. Chem. Soc. Rev. 1998, 27, 213; (d) Yang, X.
H.; Zhang, P. H.; Zhou, Y. H.; Wang, J. S.; Liu, H. J. Chin. J. Chem.
[10] Nagariya, A. K.; Meena, A. K.; Yadav, A. K.; Niranjan, U. S.;
Pathak, A. K.; Singh, B.; Rao, M. M. J. Pharm. Res. 2010, 3, 575.
[11] Kappe, C. O.; Dallinger, D.; Murphree, S. S. Practical Microwave
Synthesis for Organic Chemists, Wiley-VCH, Weinheim, 2009.
[12] Kappe, C. O. Chem. Sov. Rev. 2008, 37, 1127.
(Cheng, F.)
6
www.cjc.wiley-vch.de
© 2012 SIOC, CAS, Shanghai, & WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
Chin. J. Chem. 2012, XX, 1—6