Divergent products obtained from the reactions of salicylaldehyde and 4-hydroxycoumarin in TEBAC-H2O, KF-Al2 O3-EtOH, and Ionic Liquid

Article abstract of DOI:10.1080/00397910903419837

Controlling selectivity of the reactions of salicylaldehydes and 4-hydroxycoumarin in triethylbenzylammonium chloride-H₂^O, ionic liquid, or KF-Al₂^O₃-EtOH systems, respectively, resulted in the synthes

Full text of DOI:10.1080/00397910903419837

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Divergent Products Obtained from the
Reactions of Salicylaldehyde and 4-
Hydroxycoumarin in TEBAC-H2O, KF-
Al2O3-EtOH, and Ionic Liquid
Xiang-Shan Wang a b , Jie Zhou a , Ke Yang a & Mei-Mei Zhang b
a School of Chemistry and Chemical Engineering, Xuzhou Normal
University, Xuzhou, Jiangsu, China
b Key Laboratory of Biotechnology for Medical Plants, Xuzhou,
Jiangsu, China
Version of record first published: 15 Oct 2010.
To cite this article: Xiang-Shan Wang , Jie Zhou , Ke Yang & Mei-Mei Zhang (2010): Divergent Products
Obtained from the Reactions of Salicylaldehyde and 4-Hydroxycoumarin in TEBAC-H2O, KF-Al2O3-EtOH,
and Ionic Liquid, Synthetic Communications: An International Journal for Rapid Communication of
Synthetic Organic Chemistry, 40:22, 3332-3345
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Synthetic Communications1, 40: 3332–3345, 2010
Copyright # Taylor & Francis Group, LLC
ISSN: 0039-7911 print=1532-2432 online
DOI: 10.1080/00397910903419837
DIVERGENT PRODUCTS OBTAINED FROM
THE REACTIONS OF SALICYLALDEHYDE AND
4-HYDROXYCOUMARIN IN TEBAC-H2O,
KF-Al2O3-EtOH, AND IONIC LIQUID
Xiang-Shan Wang,1,2 Jie Zhou,1 Ke Yang,1 and
Mei-Mei Zhang2
1School of Chemistry and Chemical Engineering, Xuzhou Normal University,
Xuzhou, Jiangsu, China
2Key Laboratory of Biotechnology for Medical Plants, Xuzhou,
Jiangsu, China
Controlling selectivity of the reactions of salicylaldehydes and 4-hydroxycoumarin in
triethylbenzylammonium chloride–H2O, ionic liquid, or KF-Al2O3-EtOH systems, respect-
ively, resulted in the syntheses of three series of different coumarin derivatives.
Keywords: Aqueous media; coumarin; ionic liquid; KF-Al2O3
INTRODUCTION
Control of selectivity, for example, chemo- and regioselectivity, is among the
most important objectives in organic chemistry. Many different process parameters
such as temperature, pressure, solvent, catalyst type, and other factors can be utilized
to modulate the selectivity of synthetic transformations.[1] Multicomponent reactions
(MCRs) can be distinguished from classical, sequential two-component chemistry
synthetic processes in that they use three or more chemical starting materials as
the input for product formation. Up to seven starting components have been used,
and MCRs have often been shown to produce greater product yields than classical
chemistry.[2] For multicomponent reactions involving the simultaneous molecular
interaction of three or more components, the issue of selectivity is of particular
significance because of the high probability of several potential parallel reaction
pathways leading to different product classes.[3] They also provide a powerful tool
for the one-pot synthesis of diverse and complex compounds as well as small and
druglike heterocycles.[4]
Compounds containing coumarin moieties are ubiquitous to a variety of
important compounds and potent drugs, including a number of HIV protease
inhibitors.[5] Besides, they are known to display a wide range of biological activities,
Received April 15, 2009.
Address correspondence to Xiang-Shan Wang, School of Chemistry and Chemical Engineering,
Xuzhou Normal University, Xuzhou, Jiangsu, 221116, China. E-mail: xswang1974@yahoo.com
3332

REACTION OF SALICYLALDEHYDE AND 4-HYDROXYCOUMARIN
3333
including anti-angiogenesis activity,[6] antimicrobial activity,[7] anticoagulant
activity,[8] antibacterial activity,[9] and anti-inflammatory activity.[10] As part of
our ongoing research about the synthesis of bioactive compounds,[11] herein we
report the reactions of aromatic aldehyde and 4-hydroxycoumarin by controlling
selectivity of MCRs in triethylbenzylammonium chloride (TEBAC)–H2O, ionic
liquid, or KF-Al2O3-EtOH systems, respectively, resulting in five series of different
coumarin derivatives.
RESULTS AND DISCUSSION
In our initial study, we tested the reaction of salicylaldehyde 1 with 2 equiv. of 4-
hydroxycoumarin 2 in EtOH at 80 ꢀC (Scheme 1). A small amount of piperidine was
added to enhance the rate of conversion. The interesting 2,7,10-trioxaanthracene-1-
,8-dione derivatives 3 were isolated. Obviously, this structure, 3, was different from
the simple dehydrated aldol product 4 reported by Sullivan et al.[12] in 1943 for the
reaction carried out in refluxing EtOH without added base. The structure of 3d is
further confirmed by x-ray diffraction and is shown in Fig. 1.
Using the conversion of salicylaldehyde and 4-hydroxycoumarin as a model
reaction; different solvents such as CH3CN, CH3OH, and dimethylformamide
(DMF) and various bases such as NaOH, KOH, K2CO3, Et3N, piperidine and
KF-Al2O3 were used to optimize the conditions. This resulted in 2,7,10-
trioxaanthracene-1,8-dione compound 3a as the only product in good yields
(Table 1). An optimized yield of 84% was obtained in the presence of 100 mol% of
KF-Al2O3 in EtOH (Table 1, entry 6). Subsequently, these optimized conditions
were applied for the conversion of various substituted salicylaldehydes 1 into the
corresponding fused biscoumarine analogs 3b–g (Table 2).
To obtain the products by a green method, we performed the same reaction in
water in the presence of 5 mol% TEBAC at room temperature. To our disappoint-
ment, only the simple Knoevenagel condensation products 4 were obtained, which
failed to react with another molecule of 4-hydroxycoumarin (Scheme 2). Noticeably,
the reaction of various substituted salicylaldehydes 1 selectively furnished (E)-3-
-(2-hydroxybenzylidene)-3H-chromene-2,4-dione derivatives 4a–h in good yields
(Table 3). These results are in accordance with those reported by Sullivan et al.[12]
and are listed in Table 3.
As a comparison experiment, we also tested the same reactants using the ionic
liquid [BMIM]Br as another green solvent. Interestingly, under these conditions,
Scheme 1. Reaction of salicylaldehyde and 4-hydroxycoumarin in KF-Al2O3-EtOH.

3334
X.-S. WANG ET AL.
Figure 1. Crystal structure of 3d with DMF solvate.
salicylaldehyde did react with two molecules of 4-hydroxycoumarin, affording
the 6H,7H-7-(4-hydroxy-3-coumaranyl)[1]benzopyrano[4,3-b][1]benzopyran-6-one
derivative 5a in excellent yield (Scheme 3). This result also accords with that reported
by Sullivan et al. in refluxing EtOH.[12]
Various substituted salicylaldehydes 1 were then subjected to reaction with
4-hydroxycoumarin to generate a series of benzopyrano[4,3-b][1]benzopyran-6-one
derivatives 5 (Table 4). For aldehyde 1, the yields of 5 were not sensitive to the
electronic properties of the aromatic ring in the presence of electron-withdrawing
Table 1. Synthesis of 3a under different reaction conditionsa
Entry
Solvents
Catalysts
Mol %
Yields=(%)b
1
2
EtOH
EtOH
EtOH
EtOH
EtOH
EtOH
EtOH
EtOH
CH3CN
CH3OH
DMF
Piperidine
Et3N
NaOH
100
100
100
100
100
100
50
68
72
54
62
74
84
70
84
79
82
82
3
4
KOH
K2CO3
5
6
KF-Al2O3
KF-Al2O3
KF-Al2O3
KF-Al2O3
KF-Al2O3
KF-Al2O3
7
8
200
100
100
100
9
10
11
aReagents and conditions: salicylaldehyde 1 (0.122 g, 1 mmol), 4-hydroxycoumarin 2 (0.324 g, 2 mmol),
solvent (10 mL).
bIsolated yields.

REACTION OF SALICYLALDEHYDE AND 4-HYDROXYCOUMARIN
3335
a
Table 2. Reaction of salicylaldehyde 1 and 4-hydroxycoumarin 2 in EtOH catalyzed by KF-Al2O3
Entry
R
Products
Time (h)
Yields (%)b
1
2
3
4
5
6
7
H
5-Cl
3a
3b
3c
3d
3e
3f
14
12
14
10
10
12
16
84
82
86
82
78
88
79
5-Br
5-NO2
3,5-Cl2
3,5-Br2
4-OCH3
3g
aReagents and conditions: 1 (1 mmol), 2 (0.324 g, 2 mmol), KF-Al2O3 (0.102 g, 1 mmol), and EtOH
(10 mL).
bIsolated yields.
Scheme 2. Reaction of salicylaldehyde and 4-hydroxycoumarin in water.
groups (such as halide, nitro) or electron-donating groups (such as alkyl group,
or alkoxyl group) (Table 4). The structure of 5a was further confirmed by x-ray
diffraction (Fig. 2).
Although the detailed mechanisms of these reactions have not been clarified,
the formation of coumarin derivatives 3, 4, and 5 could be explained by a possible
mechanism as presented in Scheme 4. The Knoevenagel condensation of salicylalde-
hyde and 4-hydroxycoumarin may occur to generate (E)-3-(2-hydroxy benzylidene)-
3H-chromene-2,4-dione 4 first, and then another 4-hydroxycoumarin attacks 4
to produce bis-(4-hydroxy-2-oxo-2H-chromen-3-yl)-(2-hydrophenyl) methane I.
In the ionic liquid, the intramolecular nucleophilic addition between the hydroxyl
Table 3. Reaction of salicylaldehyde 1 and 4-hydroxycoumarin 2 in water catalyzed by TEBACa
Entry
R
Products
Time (h)
Yields (%)b
1
2
3
4
5
6
7
8
H
5-Cl
4a
4b
4c
4d
4e
4f
12
10
14
18
18
16
12
18
76
78
87
74
73
80
78
75
5-Br
5-Me
4-OMe
5,6-(CH¼CH)2-
3,5-Cl2
3,5-(CMe3)2
4g
4h
aReagents and conditions: 1 (1 mmol), 2 (0.162 g, 1 mmol), TEBAC (0.023 g, 0.1 mmol), water (10 mL).
bIsolated yields.

3336
X.-S. WANG ET AL.
Scheme 3. Reaction of salicylaldehyde and 4-hydroxycoumarin in ionic liquid.
Table 4. Reaction of salicylaldehyde 1 and 4-hydroxycoumarin 2 in ionic liquida[17]
Entry
R
Products
Time=h
Yields=%b
1
2
3
4
5
6
7
8
9
H
5-Cl
5a
5b
5c
5d
5e
5f
8
6
86
84
89
78
92
90
82
85
81
5-Br
5-NO2
10
6
3,5-Cl2
3,5-Br2
5-Me
6
6
5g
5h
5i
12
10
10
4-OMe
5,6-(CH¼CH)2-
aReagents and conditions: salicylaldehyde 1 (1 mmol), 2 (0.324 g, 2 mmol), and [BMIM]Br (2 mL).
bIsolated yields.
Figure 2. Crystal structure of the product 5a with another molecule and two molecules of EtOH, with
monohydration deleted for clarity.

REACTION OF SALICYLALDEHYDE AND 4-HYDROXYCOUMARIN
3337
Scheme 4. Possible mechanism of the formation of coumarin derivatives 3, 4, and 5.
group of phenol and the carbonyl group in coumarin takes place to give II, which
is followed by dehydration to yield the final product 5. While in the KF-Al2O3-EtOH
system, the enol of coumarin in the Michael addition product of I is changed
into anion rather than the hydroxyl group of phenol, which then attacks another
carbonyl group to give III, which finally loses one molecule of water to result in 3.
To gain more insight into the reaction mechanism, we performed the reaction
of (E)-3-(2-hydroxybenzylidene)-3H-chromene-2,4-dione 4a and 4-hydroxycoumarin
2 in ionic liquid and KF-Al2O3-EtOH, respectively. To our delight, the designed
reaction proceeded smoothly to give 9-(2-hydroxylphenyl)-9H-dibenzo[c,h]-2,7,10-
tioxanthene-1,8-dione 3a and 6H,7H-7-(4-hydroxy-3-coumaranyl)[1]benzopyrano
[4,3-b] [1]benzopyran-6-one 5a in good yields (Scheme 5). This result may indicate
that the Michael addition takes place in these reactions.
Scheme 5. Reaction of (E)-3-(2-hydroxybenzylidene)-3H-chromene-2,4-dione, 4-hydroxycoumarin in
KF-Al2O3-EtOH and ionic liquid.

3338
X.-S. WANG ET AL.
CONCLUSION
In conclusion, we controlled the selectivity of the interesting reactions of
salicylaldehydes and 4-hydroxycoumarin in TEBAC-H2O, ionic liquid, or KF-
Al2O3-EtOH systems, respectively, resulting in (E)-3-arylidene-3H-chromene-
2,4-dione derivatives, 6H,7H-7-(4-hydroxy-3-coumaranyl)[1]benzopyrano[4,3-b][1]
benzopyran-6-one derivatives, and 2,7,10-trioxaanthracene-1,8-dione derivatives,
respectively. The features of this procedure are mild reaction conditions, good to
excellent yields, and operational simplicity.
EXPERIMENTAL
Melting points were determined in open capillaries and are uncorrected.
Infrared (IR) spectra were recorded on a Tensor 27 spectrometer in KBr pellets.
1H NMR spectra were obtained from a solution in dimethylsulfoxide (DMSO-d6)
or CDCl3 with Me4Si as internal standard using a Bruker 400 spectrometer. High-
resolution mass spectrometry (HRMS) was carried out using
MicroTOF-Q-MS analyzer.
a Bruker
General Procedure for the Syntheses of
2,7,10-Trioxaanthracene-1,8-dione Derivatives
A
dry 100-mL flask was charged with salicylaldehyde 1 (1 mmol),
4-hydroxycoumarin 2 (0.324 g, 2 mmol), KF=Al2O3 (0.102 g), and EtOH (10 mL).
The mixture was stirred at 80 ꢀC for 10–16 h. After being cooled to room tempera-
ture, the solid material was filtered off, and the crude product was purified by
recrystallization from dimethylformamide (DMF) and water to give 3.
Selected Data
9-(2-Hydroxylphenyl)-9H-dibenzo[c,h]-2,7,10-tioxanthene-1,8-dione
3a. Mp 230–232 ꢀC. IR (KBr): 3418, 1661, 1608, 1556, 1453, 1404, 1278, 1244, 1184,
1
1109, 1048, 948, 905, 862, 817, 758 cmꢁ1. H NMR (DMSO-d6, 400 MHz): 6.15 (s,
1H, CH), 6.58–6.62 (m, 2H, ArH), 6.88–6.91 (m, 1H, ArH), 7.13 (d, J ¼ 7.6 Hz, 1H,
ArH), 7.20–7.23 (m, 4H, ArH), 7.45–7.49 (m, 2H, ArH), 7.79–7.81 (m, 2H, ArH).
HRMS (ESI, m=z): calcd for C25H14NaO6 (M þ Naþ) 433.0688; found 433.0688.
9-(2-Hydroxyl-5-chlorophenyl)-9H-dibenzo[c,h]-2,7,10-tioxanthene-1,8-
dione 3b. Mp 228–230 ꢀC. IR (KBr): 3077, 1662, 1608, 1557, 1410, 1273, 1184,
1113, 1044, 913, 818, 761 cmꢁ1 1H NMR (DMSO-d6, 400 MHz): 6.13 (s, 1H,
.
CH), 6.60 (d, J ¼ 8.4 Hz, 1H, ArH), 6.95 (dd, J ¼ 8.4 Hz, J0 ¼ 2.4 Hz 1H, ArH),
7.06 (d, J ¼ 2.4 Hz, 1H, ArH), 7.21–7.24 (m, 4H, ArH), 7.47–7.50 (m, 2H, ArH),
7.81–7.83 (m, 2H, ArH). HRMS (ESI, m=z): calcd. for C25H13ClO6Na (M þ Naþ)
467.0298; found 467.0262.
9-(2-Hydroxyl-5-bromophenyl)-9H-dibenzo[c,h]-2,7,10-tioxanthene-1,8-
dione 3c. Mp 228–230 ꢀC. IR (KBr): 3463, 1670, 1607, 1559, 1475, 1407, 1273,
.
1184, 1111, 1042, 909, 817, 762 cmꢁ1 1H NMR (DMSO-d6, 400 MHz): 6.13

REACTION OF SALICYLALDEHYDE AND 4-HYDROXYCOUMARIN
3339
(s, 1H, CH), 6.57 (d, J ¼ 8.4 Hz, 1H, ArH), 7.07 (dd, J ¼ 8.4 Hz, J0 ¼ 2.0 Hz, 1H,
ArH), 7.19–7.24 (m, 5H, ArH), 7.47–7.51 (m, 2H, ArH), 7.82 (d, J ¼ 8.0 Hz, 2H,
ArH). 13C NMR (DMSO-d6, 100 MHz): 33.0, 103.1, 109.3, 115.3, 116.7, 120.1,
122.8, 124.0, 128.6, 130.6, 131.4, 132.0, 152.4, 154.5, 164.0, 167.2. HRMS (ESI,
m=z): calcd. for C25H13BrO6Na (M þ Naþ) 510.9793; found 510.9764.
9-(2-Hydroxyl-5-nitrophenyl)-9H-dibenzo[c,h]-2,7,10-tioxanthene-1,8-
dione 3d. Mp 251–253 ꢀC. IR (KBr): 3567, 1670, 1607, 1558, 1497, 1431, 1405,
1
1338, 1284, 1240, 1184, 1109, 1085, 1043, 931, 898, 763 cmꢁ1. H NMR (DMSO-
d6, 400 MHz): 6.20 (s, 1H, CH), 6.79 (d, J ¼ 8.8 Hz, 1H, ArH) 7.22–7.26 (m, 4H,
ArH), 7.48–7.52 (m, 2H, ArH), 7.82 (d, J ¼ 7.2 Hz, 2H, ArH), 7.93 (dd, J ¼ 8.8 Hz,
J0 ¼ 2.8 Hz, 1H, ArH), 8.04 (d, J ¼ 2.0 Hz, 1H, ArH). HRMS (ESI, m=z): calcd. for
C25H13NO6Na (M þ Naþ) 478.0539; found 478.0523.
9-(2-Hydroxyl-3,5-dichlorophenyl)-9H-dibenzo[c,h]-2,7,10-tioxanthene-
1,8-dione 3e. Mp 238–240 ꢀC. IR (KBr): 3410, 1664, 1607, 1541, 1458, 1407, 1330,
1
1274, 1182, 1110, 1047, 917, 853, 800, 762 cmꢁ1. H NMR (DMSO-d6, 400 MHz):
6.23 (s, 1H, CH), 7.08 (s, 1H, ArH), 7.22–7.25 (m, 5H, ArH), 7.48–7.52 (m, 2H,
ArH), 7.82 (d, J ¼ 8.0 Hz, 2H, ArH). HRMS (ESI, m=z): calcd. for C25H12Cl2O6Na
(M þ Naþ) 500.9909; found 500.9890.
9-(2-Hydroxyl-3,5-dibromophenyl)-9H-dibenzo[c,h]-2,7,10-tioxanthene-
1,8-dione 3f. Mp 250–252 ꢀC. IR (KBr): 3205, 1656, 1604, 1540, 1453, 1402, 1332,
.
1274, 1250, 1232, 1181, 1137, 1111, 1045, 913, 856, 798, 767 cmꢁ1 1H NMR
(DMSO-d6, 400 MHz): 6.25 (s, 1H, CH), 7.22–7.25 (m, 5H, ArH), 7.46–7.52
(m, 3H, ArH), 7.83 (d, J ¼ 8.0 Hz, 2H, ArH). HRMS (ESI, m=z): calcd. for
C25H12Br2O6Na (M þ Naþ) 588.8898; found 590.8866.
9-(2-Hydroxyl-4-methoxxyphenyl)-9H-dibenzo[c,h]-2,7,10-tioxanthene-
1,8-dione 3g. Mp 194–196 ꢀC. IR (KBr): 3446, 1669, 1607, 1558, 1428, 1404, 1374,
1
1289, 1202, 1110, 1040, 950, 904, 839, 762 cmꢁ1. H NMR (DMSO-d6, 400 MHz):
3.62 (s, 3H, CH3O), 6.09 (s, 1H, CH), 6.19–6.21 (m, 2H, ArH), 7.02 (d, J ¼ 8.0 Hz,
1H, ArH), 7.19–7.22 (m, 4H, ArH), 7.44–7.48 (m, 2H, ArH), 7.80 (d, J ¼ 7.6 Hz, 2H,
ArH). HRMS (ESI, m=z): calcd. for C26H16O7Na (M þ Naþ) 463.0794; found
463.0774.
General Procedure for the Syntheses of (E)-3-(2-Hydroxybenzylidene)-
3H-chromene-2,4-dione Derivatives 4
A 50-mL flask was charged with salicylaldehyde 1 (1.0 mmol), 4-hydroxycou-
marin 2 (0.162 g, 1.0 mmol), TEBAC (0.1 mmol, 0.023 g), and water (10 mL). The
reaction mixture was stirred at 90 ꢀC for 10–18 h; the solid was isolated by filtration.
The filtrate, together with TEBAC, could be used directly for the same reaction. The
crude products were washed with water and purified by recrystallization from EtOH
to give 4.

3340
X.-S. WANG ET AL.
Selected Data
(E)-3-(2-Hydroxybenzylidene)-3H-chromene-2,4-dione 4a. Mp 176–177 ꢀC
(lit.[12] 174–175 ꢀC). IR (KBr): 3463, 1718, 1628, 1607, 1592, 1568, 1456, 1440,
1
1346, 1313, 1277, 1243, 1215, 1173, 1123, 1039, 941, 810, 767, 745 cmꢁ1. H NMR
(DMSO-d6, 400 MHz): 6.90–6.97 (m, 2H, ArH), 7.40–7.50 (m, 3H, ArH),
7.67–7.74 (m, 2H, ArH), 7.87 (d, J ¼ 7.6 Hz, 1H, ArH), 8.32 (s, 1H, CH), 10.77 (s,
1H, OH). HRMS (ESI, m=z): calcd. for C16H10O4Na (M þ Naþ) 289.0477; found
289.0477.
(E)-3-(2-Hydroxy-5-chlorobenzylidene)-3H-chromene-2,4-dione 4b. Mp
188–190 ꢀC. IR (KBr): 3449, 1719, 1627, 1608, 1568, 1479, 1456, 1354, 1340, 1307,
1239, 1211, 1168, 1151, 1046, 946, 930, 817, 733, 707. 1H NMR (DMSO-d6,
400 MHz): 6.91–6.97 (m, 2H, ArH), 7.41–7.54 (m, 2H, ArH), 7.69–7.76 (m, 2H,
ArH), 7.80 (s, 1H, ArH), 8.28 (s, 1H, ArH), 10.73 (s, 1H, OH). HRMS (ESI,
m=z): calcd. for C16H9ClO4Na (M þ Naþ) 323.0087; found 323.0083.
(E)-3-(2-Hydroxy-5-bromobenzylidene)-3H-chromene-2,4-dione 4c. Mp
186–188 ꢀC. IR (KBr): 3423, 3041, 1680, 1719, 1628, 1606, 1562, 1484, 1474, 1450,
1411, 1354, 1340, 1308, 1269, 1239, 1211, 1173, 1152, 1045, 1032, 944, 928, 815,
772, 751, 705 cmꢁ1 1H NMR (DMSO-d6, 400 MHz): 6.90–6.97 (m, 2H, ArH),
.
7.47–7.53 (m, 2H, ArH), 7.69 (d, J ¼ 7.6 Hz, 1H, ArH), 7.75 (d, J ¼ 9.2 Hz, 1H,
ArH), 7.99 (s, 1H, ArH), 8.27 (s, 1H, CH), 10.80 (s, 1H, OH). HRMS (ESI, m=z):
calcd. for C16H9BrO4Na (M þ Naþ) 366.9582; found 366.9582.
(E)-3-(2-Hydroxy-5-methylbenzylidene)-3Hh-chromene-2,4-dione 4d. Mp
186–188 ꢀC. IR (KBr): 3066, 1718, 1625, 1597, 1573, 1542, 1479, 1457, 1360, 1330,
.
1306, 1277, 1242, 1186, 932, 831, 819, 768, 722 cmꢁ1 1H NMR (DMSO-d6,
400 MHz): 2.38 (s, 3H, CH3), 6.89–6.96 (m, 2H, ArH), 7.37 (d, J ¼ 8.4 Hz, 1H,
ArH), 7.46–7.54 (m, 2H, ArH), 7.65–7.67 (m, 2H, ArH), 8.25 (s, 1H, CH), 10.76
(s, 1H, OH). HRMS (ESI, m=z): calcd. for C17H12O4Na (M þ Naþ) 303.0633; found
303.0633.
(E)-3-(2-Hydroxy-4-methoxybenzylidene)-3H-chromene-2,4-dione
4e. Mp 198–200 ꢀC. IR (KBr): 3463, 1717, 1620, 1599, 1560, 1508, 1489, 1446, 1376,
.
1340, 1311, 1283, 1238, 1206, 1160, 1122, 1027, 857, 822, 757 cmꢁ1 1H NMR
(DMSO-d6, 400 MHz): 3.89 (s, 3H, CH3O), 6.89–6.95 (m, 2H, ArH), 7.02 (dd,
J ¼ 8.8 Hz, J0 ¼ 2.0 Hz, 1H, ArH), 7.06 (s, 1H, ArH), 7.44–7.47 (m, 1H, ArH), 7.61
(d, J ¼ 7.6 Hz, 1H, ArH), 7.80 (d, J ¼ 8.4 Hz, 1H, ArH), 8.31 (s, 1H, ArH), 10.66
(s, 1H, OH). HRMS (ESI, m=z): calcd. for C17H12O5Na (M þ Naþ) 319.0582; found
319.0582.
(E)-3-(2-Hydroxy-1-naphthalenylidene)-3H-chromene-2,4-dione 4f. Mp
252–254 ꢀC. IR (KBr): 3403, 2062, 1708, 1625, 1620, 1569, 1519, 1488, 1439, 1396,
1341, 1327, 1307, 1288, 1252, 1216, 1181, 1094, 995, 951, 929, 819, 783, 748 cmꢁ1
.
1H NMR (DMSO-d6, 400 MHz): 6.93–6.99 (m, 2H, ArH), 7.48–7.52 (m, 1H,
ArH), 7.64–7.68 (m, 2H, ArH), 7.74–7.77 (m, 2H, ArH), 8.10 (d, J ¼ 8.0 Hz, 1H,
ArH), 8.31 (d, J ¼ 9.2 Hz, 1H, ArH), 8.62 (d, J ¼ 8.4 Hz, 1H, ArH), 9.11 (s, 1H,
CH), 10.83 (s, 1H, OH). HRMS (ESI, m=z): calcd. for C20H12O4Na (M þ Naþ)
339.0633; found 339.0632.

REACTION OF SALICYLALDEHYDE AND 4-HYDROXYCOUMARIN
3341
(E)-3-(2-Hydroxy-3,5-dichlorobenzylidene)-3H-chromene-2,4-dione 4g. Mp
192–194 ꢀC. IR (KBr): 3435, 3074, 1727, 1627, 1604, 1561, 1483, 1454, 1362, 1336,
.
1307, 1242, 1216, 1149, 1033, 988, 944, 926, 869, 841, 816, 766, 719 cmꢁ1 1H
NMR (DMSO-d6, 400 MHz): 6.91–6.98 (m, 2H, ArH), 7.48–7.52 (m, 1H, ArH),
7.72 (dd, J ¼ 8.0 Hz, J0 ¼ 1.6 Hz, 1H ArH), 7.99 (d, J ¼ 2.4 Hz, 1H, ArH), 8.05 (d,
J ¼ 2.4 Hz, 1H, ArH), 8.30 (s, 1H, ArH), 10.79 (s, 1H, OH). HRMS (ESI, m=z):
calcd. for C16H9Cl2O4 (M þHþ) 334.9878; found 334.9878.
(E)-3-(2-Hydroxy-3,5-di-t-butylbenzylidene)-3H-chromene-2,4-dione
1
4h. Mp 225–227 ꢀC. H NMR (DMSO-d6, 400 MHz): 1.33 (s, 9H, 3CH3), 1.48 (s,
9H, 3CH3) 6.93–6.95(m, 2H, ArH), 7.47–7.51 (m, 1H, ArH), 7.64–7.69 (m, 2H,
ArH), 7.76 (s, 1H, ArH), 8.32 (s, 1H, CH), 10.68 (s, 1H., OH). IR (KBr): 3012,
2964, 2871, 1714, 1632, 1603, 1580, 1444, 1398, 1370, 1341, 1306, 1272, 1217,
1172, 1058, 1032, 999, 960, 935, 907, 898, 873, 815, 762, 739 cmꢁ1. HRMS (ESI,
m=z): calcd. for C24H27O4 (M þHþ) 379.1909; found 379.1890.
General Procedure for the Syntheses of 6H,7H-7-(4-Hydroxy-
3-coumaranyl)[1]benzopyrano[4,3-b][1]benzopyran-6-one
Derivatives 5
A dry 50-mL flask was charged with salicylaldehyde (2.0 mmol), 4-hydroxycou-
marin (0.324 g, 2.0 mmol), and ionic liquid of [bmimþ][Br-] (2 mL). The reaction mix-
ture was stirred at 90 ꢀC for 6–12 h. Five mL water were then added to the mixture,
and the solid was isolated by filtration. The water in the filtrate was removed by
evaporation at reduced pressure, and the ionic liquid in could be recovered easily
at 80 ꢀC in a vacuum for 4 h. The crude yellow products were washed with water
and purified by recrystallization from DMF to give 5.
Selected Data
6H,7H-7-(4-Hydroxy-3-coumaranyl)[1]benzopyrano[4,3-b][1]benzopyran-
6-one 5a. Mp 240–242 ꢀC. IR (KBr): 2972, 1699, 1645, 1610, 1567, 1488, 1455,
1
1390, 1276, 1242, 1221, 1106, 1044, 979, 905, 866, 757 cmꢁ1. H NMR (DMSO-d6,
400 MHz): 5.75 (s, 1H, CH), 7.13–7.17 (m, 1H, ArH), 7.21 (d, J ¼ 7.2 Hz, 1H,
ArH), 7.31–7.36 (m, 4H, ArH), 7.46 (d, J ¼ 8.0 Hz, 1H, ArH), 7.49 (t, J ¼ 8.0 Hz,
1H, ArH), 7.58–7.62 (m, 1H, ArH), 7.68–7.73 (m, 1H, ArH), 8.03–8.12 (m, 2H,
ArH). HRMS (ESI, m=z): calcd. for C25H14NaO6 (M þ Naþ) 433.0688; found
433.0659.
9-Chloro-6H,7H-7-(4-hydroxy-3-coumaranyl)[1]benzopyrano[4,3-b][1]-
benzopyran-6-one 5b. Mp > 300 ꢀC. IR (KBr): 3269, 3051, 1709, 1671, 1643,
1631, 1608, 1572, 1496, 1479, 1454, 1393, 1303, 1244, 1220, 1183, 1166, 1110,
1
1070, 1058, 881, 833, 796, 760, 748 cmꢁ1. H NMR (DMSO-d6, 400 MHz): 5.72 (s,
1H, CH), 7.18 (s, 1H, ArH), 7.32–7.51 (m, 6H, ArH), 7.60–7.64 (m, 1H, ArH),
7.69–7.73 (m, 1H, ArH), 8.03–8.11 (m, 2H, ArH). HRMS (ESI, m=z): calcd. for
C25H13ClO6Na (M þ Naþ) 467.0298; found 467.0293.

3342
X.-S. WANG ET AL.
9-Bromo-6H,7H-7-(4-hydroxy-3-coumaranyl)[1]benzopyrano[4,3-b][1]-
benzopyran-6-one 5c. Mp > 300 ꢀC. IR (KBr): 3273, 3057, 1700, 1672, 1643, 1569,
1496, 1478, 1455, 1334, 1303, 1284, 1220, 1167, 1152, 1109, 1068, 985, 906, 879, 832,
797, 766, 748 cmꢁ1. 1H NMR (DMSO-d6, 400 MHz): 5.72 (s, 1H, CH), 7.31–7.38 (m,
4H, ArH), 7.44–7.53 (m, 3H, ArH), 7.60–7.648 (m, 1H, ArH), 7.69–7.73 (m, 1H,
ArH), 8.05–8.10 (m, 2H, ArH). HRMS (ESI, m=z): calcd. for C25H13BrO6Na
(M þ Naþ) 510.9793; found 510.9725.
9-Nitro-6H,7H-7-(4-hydroxy-3-coumaranyl)[1]benzopyrano[4,3-b][1]-
benzopyran-6-one 5d. Mp > 300 ꢀC. IR (KBr): 3309, 3072, 1703, 1670, 1646,
1629, 1609, 1523, 1496, 1455, 1392, 1337, 1286, 1243, 1218, 1185, 1111, 1090,
.
1059, 904, 848, 754 cmꢁ1 1H NMR (DMSO-d6, 400 MHz): 5.82 (s, 1H, CH),
7.22–7.26 (m, 4H, ArH), 7.32–7.57 (m, 4H, ArH), 7.60–7.64 (m, 2H, ArH),
7.71–7.28 (m, 1H, ArH), 8.02–8.08 (m, 2H, ArH), 8.14 (d, J ¼ 7.6 Hz, 1H, ArH),
8.24 (dd, J ¼ 8.8 Hz, J0 ¼ 1.2 Hz, 1H, ArH). HRMS (ESI, m=z): calcd. for
C25H13NO8Na (M þ Naþ) 478.0539; found 478.0514.
9,11-Dichloro-6H,7H-7-(4-hydroxy-3-coumaranyl)[1]benzopyrano[4,3-b]-
[1]benzopyran-6-one 5e. Mp > 300 ꢀC. IR (KBr): 3077, 1697, 1662, 1639, 1610,
1570, 1494, 1456, 1396, 1341, 1315, 1216, 1188, 1108, 1079, 1050, 953, 913, 860,
1
806, 759 cmꢁ1. H NMR (DMSO-d6, 400 MHz): 5.71 (s, 1H, CH), 7.15 (s, 1H,
ArH), 7.32–7.39 (m, 2H, ArH), 7.43–7.51 (m, 2H, ArH), 7.59–7.62 (m, 2H, ArH),
7.68–7.72 (m, 1H, ArH), 7.96–8.04 (m, 2H, ArH). HRMS (ESI, m=z): calcd. for
C25H12Cl2O6 (M þHþ) 500.9909; found 500.9895.
11-Dibromo-6H,7H-7-(4-hydroxy-3-coumaranyl)[1]benzopyrano[4,3-b][1]-
benzopyran-6-one 5f. Mp > 300 ꢀC. IR (KBr): 3073, 1698, 1661, 1639, 1611, 1568,
1494, 1452, 1393, 1341, 1315, 1271, 1238, 1219, 1166, 1108, 1076, 1047, 941, 913, 914,
860, 804, 760, 731 cmꢁ1 1H NMR (DMSO-d6, 400 MHz): 5.72 (s, 1H, CH),
.
7.30–7.37 (m, 3H, ArH), 7.46 (d, J ¼ 8.0 Hz, 1H, ArH), 7.50–7.54 (m, 1H, ArH),
7.60–7.63 (m, 1H, ArH), 7.70–7.74 (m, 1H, ArH), 7.86 (s, 1H, ArH), 8.01 (d,
J ¼ 8.0 Hz, 1H, ArH). 13C NMR (DMSO-d6, 100 MHz): 29.1, 111.1, 113.3, 116.1,
116.3, 116.6, 116.8, 122.2, 123.9, 124.0, 124.1, 124.8, 126.3, 130.4, 132.4, 132.8,
133.7, 145.5, 151.9, 152.3, 155.6, 159.9, 161.47, 161.52, 161.54. HRMS (ESI, m=z):
calcd. for C25H12Br2O6Na (M þ Naþ) 588.8898; found 588.8854.
9-Methyl-6H,7H-7-(4-hydroxy-3-coumaranyl)[1]benzopyrano[4,3-b][1]-
1
benzopyran-6-one 5g. Mp 291–293 ꢀC. H NMR (DMSO-d6, 400 MHz): 2.21 (s,
3H, CH3), 5.71 (s, 1H, CH), 7.10 (d, J ¼ 8.0 Hz, 1H, ArH), 7.22 (d, J ¼ 8.0 Hz,
1H, ArH), 7.31–7.37 (m, 2H, ArH), 7.43–7.49 (m, 2H, ArH), 7.58–7.62 (m, 1H,
ArH), 7.66–7.70 (m, 1H, ArH), 8.07 (d, J ¼ 8.0 Hz, 1H, ArH). IR (KBr): 1715,
1667, 1632, 1608, 1574, 1490, 1454, 1394, 1304, 1215, 1174, 1149, 1108, 1074,
1055, 905, 883, 832, 798, 766, 747 cmꢁ1. HRMS (ESI, m=z): calcd. for C26H16O6Na
(M þ Naþ) 447.0845; found 447.0826.
10-Methoxy-6H,7H-7-(4-hydroxy-3-coumaranyl)[1]benzopyrano[4,3-b][1]-
benzopyran-6-one 5h. Mp > 300 ꢀC (lit.[12]: 310–304 ꢀC). IR (KBr): 3068, 1717,
1673, 1650, 1624, 1586, 1568, 1494, 1455, 1387, 1330, 1277, 1201, 1166, 1145,
1108, 1068, 1032, 976, 947, 902, 829, 789, 755 cmꢁ1 1H NMR (DMSO-d6,
.

REACTION OF SALICYLALDEHYDE AND 4-HYDROXYCOUMARIN
3343
400 MHz): 3.79 (s, 3H, CH3O), 5.66 (s, 1H, CH), 6.74 (dd, J ¼ 8.4 Hz, J0 ¼ 1.6 Hz,
1H, ArH), 6.95 (d, J ¼ 1.6 Hz, 1H, ArH), 7.09 (d, J ¼ 8.4 Hz, 1H, ArH), 7.04–7.37
(m, 2H, ArH), 7.44–7.51 (m, 2H, ArH), 7.58–7.62 (m, 1H, ArH), 7.68–7.72 (m,
1H, ArH), 8.06–8.12 (m, 2H, ArH). HRMS (ESI, m=z): calcd. for C26H16O7Na
(M þ Naþ) 463.0794; found 463.0796.
6h,7H-7-(4-hydroxy-3-coumaranyl)[1]-benzo[f]benzopyrano[4,3-b][1]-
benzopyran-6-one 5i. Mp > 300 ꢀC. IR (KBr): 2930, 1719, 1694, 1653, 1607, 1568,
1490, 1455, 1385, 1311, 1289, 1229, 1213, 1106, 1051, 1030, 929, 859, 819, 753 cmꢁ1
.
1H NMR (DMSO-d6, 400 MHz): 6.20 (s, 1H, CH), 7.25–7.61 (m, 8H, ArH),
7.68–7.72 (m, 1H, ArH), 7.92–7.98 (m, 3H, ArH), 8.12–8.17 (m, 2H, ArH). HRMS
(ESI, m=z): calcd. for C29H16O6Na (M þ Naþ) 483.0845. found 483.0860.
Crystal Data for 3d
C28H20N2O9; M ¼ 528.46, pale yellow block crystals, 0.26ꢂ 0.22ꢂ 0.20mm, tri-
˚
clinic, space group P-1, a ¼ 10.210 (3), b ¼ 10.698 (4), c ¼ 12.522 (4) A, a ¼ 92.214 (ꢁ63),
3
ꢀ
˚
b ¼ 113.751 (5), c ¼ 105.040 (5) , V ¼ 1193.0 (7) A , Z ¼ 2, Dc ¼ 1.471 gcm
.
F (000) ¼ 548, m (MoKa) ¼ 0.112 mmꢁ1. Intensity data were collected on a charge
coupled device (CCD) area detector with graphite monochromated MoKa radiation
ꢀ
ꢀ
˚
(k ¼ 0.71073 A) using phi and omega scan modes with 1.80 <h < 25.02 ; 4178 unique
reflections were measured and 2667 reflections with I > 2r (I) were used in the refine-
ment. Structure was solved by direct methods and expanded using Fourier techniques.
The final cycle of full-matrix least squares technique was to R ¼ 0.0444 and
wR ¼ 0.1373.
Crystal Data for 5a
C54H42O15; M ¼ 930.88, pale yellow block crystals, 0.259 ꢂ 0.184 ꢂ 0.101 mm,
monoclinic, space group P2(1)=c, a ¼ 18.6254 (3), b ¼ 15.2692 (2), c ¼ 17.7026 (2)
3
A, b ¼ 115.534 (1) , V ¼ 4542.80 (11) A , Z ¼ 2, Dc ¼ 1.361 gcmꢁ3. F (000) ¼ 1944,
ꢀ
˚
˚
m (MoKa) ¼ 0.100 mmꢁ1. Intensity data were collected on a CCD area detector with
˚
graphite monochromated MoKa radiation (k ¼ 0.71073 A) using phi and omega
scans mode with 1.21ꢀ <h < 27.56ꢀ; 10426 unique reflections were measured and
4775 reflections with I > 2r (I) were used in the refinement. Structure was solved
by direct methods and expanded using Fourier techniques. The final cycle of
full-matrix least squares technique was to R ¼ 0.0568 and wR ¼ 0.1406.
ACKNOWLEDGMENTS
We are grateful to the National Natural Science Foundation of China
(20802061), the Natural Science Foundation (08KJD150019), and the Qing Lan
Project (08QLT001) of the Jiangsu Education Committee for financial support.
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