Alum-catalyzed one-pot synthesis of dihydropyrano[3,2-b]chromenediones

Article abstract of DOI:10.1590/S0103-50532011001100025

A simple, green and efficient solventless procedure for the synthesis of eleven dihydropyrano[3,2-b]chromenediones from the three-component condensation reaction of kojic acid, aromatic aldehydes, and dimedone using a reusable alum as catalyst is describe

Full text of DOI:10.1590/S0103-50532011001100025

J. Braz. Chem. Soc., Vol. 22, No. 11, 2202-2205, 2011.
Printed in Brazil - ©2011 Sociedade Brasileira de Química
0103 - 5053 $6.00+0.00
Article
A
Alum-Catalyzed One-Pot Synthesis of Dihydropyrano[3,2-b]chromenediones
Wei Lin Li, Li Qiang Wu* and Fu Lin Yan
School of Pharmacy, Xinxiang Medical University, Xinxiang, Henan 453003, P. R. China
Neste trabalho é descrito um procedimento livre de solventes, limpo, simples e eficiente para
a síntese de diidropirano[3,2-b]cromenodionas (onze derivados) a partir da reação de condensação
de três componentes de ácido kójico, aldeídos aromáticos e dimedona, utilizando alume como
catalisador reutilizável.
A simple, green and efficient solventless procedure for the synthesis of eleven
dihydropyrano[3,2-b]chromenediones from the three-component condensation reaction of kojic
acid, aromatic aldehydes, and dimedone using a reusable alum as catalyst is described.
Keywords: dihydropyrano[3,2-b]chromenedione, alum, kojic acid, solvent-free reaction
Introduction
procedure for the one-pot synthesis of 2-(hydroxymethyl)-
7,7-dimethyl-10-aryl-7,8-dihydropyrano[3,2-b]chromene-
4,9(6H,10H)-dione under mild conditions.
The rapid assembly of molecular diversity is an
important goal of synthetic organic chemistry and one of
the key paradigms of modern drug discovery. One approach
to address this challenge involves the development of
multicomponent reactions (MCR), in which three or more
reactants are combined together in a single reaction flask
to generate a product. In addition to the intrinsic atom
economy and selectivity underlying such reactions, simpler
procedures and equipment, time and energy savings, as
well as environmental friendliness have all led to a sizable
effort to design and implement MCR in both academia
and industry.1
Kojic acid derivatives, one of the important kind of fused
heterocyclic compounds, possess significant bioactivities
such as antifungal,2 anti-neoplastic,3 antiproliferative,4 anti-
HIV,5 anticonvulsant,6 anti-inflammatory,7 antioxidative,8
antibacterial,9 anticonvulsant,10 and tyrosinase inhibitory
activities.11 Therefore, the synthesis of kojic acid derivatives
has aroused great interest in the organic and medicinal
communities.
Alum (KAl(SO4)2·12H2O), which is relatively
nontoxic and inexpensive catalyst, has emerged as an
efficient alternative catalyst for a variety of prominent
organic transformations, such as the Biginelly13 and
Pechmann14 reactions and also used for the synthesis of
1,8-dioxo-octahydroxanthenes,15 isoquinolonic acids,16
trisubstituted imidazoles,17 1’H-spiro[isoindoline-1,2’-
quinazoline]-3,4’(3’H)-diones,18 1,3,4-oxadiazoles19
and 1,5-benzodiazepines.20 In this paper, we wish
to report a rapid and highly efficient method for the
synthesis of 2-(hydroxymethyl)-7,7-dimethyl-10-aryl-7,8-
dihydropyrano[3,2-b] chromene-4,9(6H,10H)-dione in the
presence of alum under solvent-free conditions (Scheme 1).
Results and Discussion
To choose optimum conditions, first, the effect of
temperature on the rate of the reaction was studied for the
preparation of the three-component condensation reaction
of kojic acid, benzaldehyde, and dimedone in presence of
10 mol% alum under solvent-free conditions (Table 1). At
Recently Reddy et al.12 reported the synthesis of
2-(hydroxymethyl)-7,7-dimethyl-10-aryl-7,8-dihydro-
pyrano[3,2-b]chromene-4,9(6H,10H)-diones using InCl3 as
a catalyst. However, this method is associated with one or
more disadvantages such as the use of an expensive, water-
intolerant and non recyclable catalyst and higher reaction
temperature. Thus, there is still need of a simple and general
o
100 C, the reaction proceeded smoothly and gave short
reaction time and high yield. Therefore, we kept the reaction
temperature at 100 °C.
Next, in the study set out to determine optimal amount
of alum, the reaction was carried out by varying the amount
of the catalyst (Table 2). Maximum yield was obtained with
10 mol% of the catalyst. Further increase in amount of alum
*e-mail: wliq870@163.com

Vol. 22, No. 11, 2011
Li et al.
2203
Ar
10
O
O
1
O
9
O
8
HO
HO
Alum
neat, 100 °C
2
3
+
ArCHO
+
7
OH
O
4
O
5
6
O
1
O
2
3
4a-4k
Scheme 1.
Table 1. Temperature optimization for the synthesis of 2-(hydroxymethyl)-
7,7-dimethyl-10-phenyl-7,8-dihydropyrano[3,2-b]chromene-
4,9(6H,10H)-dionea
Table 2. The amounts of catalyst optimization for the synthesis of
2-(hydroxymethyl)-7,7-dimethyl-10-phenyl-7,8-dihydropyrano[3,2-b]
chromene-4,9(6H,10H)-dionea
entry
1
T / oC
25
time / min
240
120
120
90
yield / %b
entry
alum / mol%
time / min
240
180
120
90
yield / %b
0
1
2
3
4
5
6
7
0
1
0
2
50
< 5
12
38
53
76
92
92
90
92
91
49
61
76
92
89
92
3
60
2
4
70
5
5
80
90
10
15
20
50
6
90
60
50
7
100
110
120
130
140
50
50
8
50
aReaction conditions: kojic acid (1 mmol); benzaldehyde (1 mmol);
dimedone (1 mmol); 100oC; without solvent. bIsolated yield.
9
40
10
11
40
40
corresponding 2-(hydroxymethyl)-7,7-dimethyl-10-aryl-
7,8-dihydropyrano[3,2-b]chromene-4,9(6H,10H)-dione,
and representative examples are shown in Table 3. All of
1 gave the expected products in high yields, either bearing
electron-withdrawing groups (such as halide, nitro) or
electron-donating groups (such as alkyl group) under the
same reaction condition. To further demonstrate the scope
and limitation of the substrates, aliphatic aldehydes, such as
phenylacetaldehyde, propionaldehyde, n-butylaldehyde and
aReaction conditions: kojic acid (1 mmol); benzaldehyde (1 mmol);
dimedone (1 mmol); alum (0.1 mmol); without solvent. bIsolated yield.
in the mentioned reaction did not has any significant effect
on the product yield.
In order to extend the above reaction (Scheme 1)
to a library system, various kinds of arylaldehydes 2
(Table 3) were subjected to react with 1 and 3 to give the
Table 3. Preparation of 2-(hydroxymethyl)-7,7-dimethyl-10-aryl-7,8-dihydropyrano[3,2-b]chromene-4,9(6H,10H)-dionea
entry
1
Ar
C6H5
time / min
product
4a
yield / %b
mp / ºC (lit.)
184-185 (186-188)12
205-206
50
50
50
40
45
50
50
60
60
60
70
92 (90, 86)c
2
4-Cl-C6H4
4b
4c
94
92
91
95
89
91
88
85
89
87
3
4-F-C6H4
161-162 (160-164)12
229-230
4
4-NO2-C6H4
3-NO2-C6H4
2-Cl-C6H4
4d
4e
5
212-213
6
4f
216-217
7
2,4-Cl2-C6H3
3,4,5-(MeO)3-C6H2
2,5-(MeO)2-C6H3
4-Me-C6H4
4-MeO-C6H4
4g
166-167
8
4h
4i
174-175
9
192-193
10
11
4j
214-215
4k
178-179 (180-182)12
aReaction conditions: kojic acid (1 mmol); aldehyde (1 mmol); dimedone (1 mmol); alum (0.1 mmol); without solvent; 100 ºC. bIsolated yield. cThe catalyst
was reused for three runs.

2204
Alum-Catalyzed One-Pot Synthesis of Dihydropyrano[3,2-b]chromenediones
J. Braz. Chem. Soc.
O
OH
O
R
O
O
HO
Alum
O
1
RCHO
+
O
2
3
5
O
R
O
R
O
O
O
O
OH
OH
O
OH
O
4
Scheme 2.
n-heptaldehyde, were used as reactants to react with kojic
acid and dimedone. However, the desired products were
not found and obtained successfully. All of the structures
were characterized by IR, 1H NMR,13C NMR, MS and
reusable catalyst was described. The reactions were carried
out under thermal solvent-free in short reaction time and
produced the corresponding products in good to excellent
yields. Also, the catalyst could be successfully recovered
and recycled at least for three runs without significant loss
in activity.
1
elemental analysis. In the H NMR spectra, there was a
missing proton, which was possibly OH. When 1H NMR
spectra were determined using DMSO-d6 instead of CDCl3
as solvent, there appeared a broad peak at d 5.54-5.36, so
that proved that our supposition was correct.
Supplementary Information
We also checked the reusability of the catalyst by
recovering the alum and using it for new runs and found
that the catalyst could be reused several times without any
decrease in the product yield. An example is shown for the
reaction of kojic acid with benzaldehyde (Table 3, 4a) and
dimedone. The catalyst can be removed from the aqueous
phase by removing the water under vacuum then washing
with EtOH and drying at rt.
Experimental details and spectroscopic data are
available free of charge at http://jbcs.sbq.org.br as
PDF file.
Acknowledgments
We are pleased to acknowledge the financial support
from Xinxiang Medical University.
The formation of products 4a-4k can be rationalized by
initial formation of heterodiene 5 by standard Knoevenagel
condensation of dimedone 3 and aromatic aldehyde 2 in the
presence of a catalytic amount of alum. Subsequent Diels
Alder-type addition of kojic acid 1 to the heterodienes 5
followed by dehydration afford the corresponding products
4a-4k (Scheme 2).
References
1. Bienayme, H.; Hulme, C.; Oddon, G.; Schmitt, P.; Chem. Eur. J.
2000, 6, 3321.
2. Balaz, S.; Uher, M.; Brtko, J.;Veverka, M.; Bransova, J.; Dobias,
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3. Novotny, L.; Rauko, P.; Abdel-Hamid, M.; Vachalkova, A.;
Neoplasma 1999, 46, 89.
Conclusions
In conclusion, an efficient protocol for the one-pot
preparation of 2-(hydroxymethyl)-7,7-dimethyl-10-aryl-
7,8-dihydropyrano[3,2-b]chromene-4,9(6H,10H)-diones
from the three-component condensation reaction of kojic
acid, aromatic aldehydes, and dimedone employing alum as
4. Fickova, M.; Pravdova, E.; Rondhal, L.; Uher, M.; Brtko, J.;
J. Appl. Toxicol. 2008, 28, 554.
5. Tanaka, R.; Tsujii, H.; Yamada, T.; Kajimoto, T.; Amano, F.;
Hasegawa, J.; Hamashima, Y.; Node, M.; Katoh, K.; Takebe,
Y.; Bioorg. Med. Chem. 2009, 17, 5238.

Vol. 22, No. 11, 2011
Li et al.
2205
6. Aytemir, M. D.; Septioglu, E.; Calis, U.; Arzneim. Forsch. 2010,
60, 22.
15. Madje, B. R.; Ubale, M. B.; Bharad, J. V.; Shingare, M. S.;
S. Afr. J. Chem. 2009, 63, 36.
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Cho, J. Y.; Bioorg. Med. Chem. Lett. 2010, 20, 6569.
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Submitted: May 25, 2011
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Monatsh. Chem. 2007, 138, 997.
Published online: October 6, 2011

J. Braz. Chem. Soc., Vol. 22, No. 11, S1-S13, 2011.
Printed in Brazil - ©2011 Sociedade Brasileira de Química
0103 - 5053 $6.00+0.00
Supplementary Information
SI
Alum-Catalyzed One-Pot Synthesis of Dihydropyrano[3,2-b]chromenediones
Wei Lin Li, Li Qiang Wu* and Fu Lin Yan
School of Pharmacy, Xinxiang Medical University, Xinxiang, Henan 453003, P. R. China
Experimental
128.8, 128.1, 127.8, 112.3, 112.2, 60.6, 50.4, 40.9, 38.4,
32.3, 29.0, 27.4. MS (ESI): m/z 353 [M+H]+. Anal. Calc.
for C21H20O5: C 71.58, H 5.72; found: C 71.65, H 5.68.
IR spectra were determined on an FTS-40 infrared
spectrometer; NMR spectra were determined on Bruker
AV-400 spectrometer at room temperature using TMS as
internal standard, coupling constants (J) were measured
in Hz. Mass spectra were recorded on a Finnigan LCQ
Advantage mass spectrometer. Elemental analyses were
performed by a Vario-III elemental analyzer. Melting
points were determined on a XT-4 binocular microscope
and were uncorrected. Commercially available reagents
were used throughout without further purification unless
otherwise stated.
2-(Hydroxymethyl)-7,7-dimethyl-10-(4-chlorophenyl)-7,8-
dihydropyrano[3,2-b]chromene-4,9(6H,10H)-dione (4b)
IR (KBr) νmax/cm-1: 3325, 2961, 2930, 2870, 1672,
1640, 1600, 1490, 1442, 1377, 1218, 1190, 1076, 1014,
1
952, 850; H NMR (CDCl3, 400 MHz) d 7.28-7.18 (m,
4H), 6.52 (s, 1H), 4.87 (s, 1H), 4.41-4.37 (m, 2H), 2.66-
2.60 (m, 2H), 2.30-2.21 (m, 2H), 1.11 (s, 3H), 1.03 (s, 3H);
13C NMR (CDCl3, 100 MHz) d 196.3, 171.4, 168.3, 164.1,
151.2, 138.9, 137.5, 133.6, 129.4, 129.0, 112.0, 111.9,
60.4, 50.3, 40.8, 37.8, 32.3, 28.9, 27.4. MS (ESI): m/z 387
[M+H]+.Anal. calc. for C21H19ClO5: C 65.20, H 4.95; found:
C 65.12, H 4.88.
General procedure for the preparation of 2-(hydroxymethyl)-
7,7-dimethyl-10-aryl- 7,8-dihydropyrano[3,2-b]chromene-
4,9(6H,10H)-diones
2-(Hydroxymethyl)-7,7-dimethyl-10-(4-florophenyl)-7,8-
dihydropyrano[3,2-b]chromene-4,9(6H,10H)-dione (4c)
IR (KBr) νmax/cm-1: 3363, 2953, 2930, 2853, 1675,
1638, 1601, 1509, 1443, 1378, 1219, 1192, 1157, 1075,
962, 845, 683; 1H NMR (CDCl3, 400 MHz) d 7.24-7.20
(m, 2H), 6.99-6.95(m, 2H), 6.52 (s, 1H), 4.87 (s, 1H),
4.40-4.36 (m, 2H), 2.65-2.61 (m, 2H), 2.25-2.22 (m, 2H),
1.10 (s, 3H), 1.03 (s, 3H). 13C NMR (CDCl3, 100 MHz)
d 196.4, 171.5, 168.3, 164.0, 160.9, 151.5, 137.4, 136.2,
129.7, 129.6, 115.8, 115.6, 112.2, 112.0, 60.4, 50.3, 40.8,
37.7, 32.3, 28.9, 27.4; MS (ESI): m/z 371 [M+H]+. Anal.
calc. for C21H19FO5: C 68.10, H 5.17; found: C 68.20,
H 5.12.
A mixture of kojic acid (1 mmol), aldehyde (1 mmol),
dimedone (1 mmol) and alum (0.1 mmol) was heated at
100 C for an appropriate time (TLC). After completion
o
of the reaction, the mixture was washed with water
(15 mL) and the crude product was purified by column
chromatography over silica gel using ethyl acetate-hexane
(7:3) as eluent. The portions were combined and solvent
evaporated under reduced pressure to provide compounds
4a-4k as solids. The solids were recrystallized from EtOH
to give pure 4a-4k as white crystals. Aqueous washings
were collected and evaporated under reduced pressure.
After removal of the water, alum was recovered.
2-(Hydroxymethyl)-7,7-dimethyl-10-phenyl-7,8-dihydro-
pyrano[3,2-b]chromene-4,9(6H,10H)-dione (4a)
IR (KBr) νmax/cm-1: 3362, 3080, 2952, 2890, 1667, 1637,
2-(Hydroxymethyl)-7,7-dimethyl-10-(4-nitrophenyl)-7,8-
dihydropyrano[3,2-b]chromene-4,9(6H,10H)-dione (4d)
IR (KBr) νmax/cm-1: 3334, 2960, 2928, 2855, 1675,
1633, 1596, 1520, 1375, 1347, 1216, 1123, 1058, 1003,
946, 867, 622. 1H NMR (CDCl3, 400 MHz) d 8.18 (d, 2H,
J 8.8 Hz), 7.47 (d, 2H, J 8.4 Hz), 6.53 (s, 1H), 5.03 (s, 1H),
4.42-4.37 (m, 2H), 2.69-2.65 (m, 2H), 2.27-2.23 (m, 2H),
1
1441, 1378, 1219, 1193, 1078, 990, 950, 712; H NMR
(CDCl3, 400 MHz) d 7.32-7.21 (m, 5H), 6.50 (s, 1H), 4.87
(s, 1H), 4.43-4.32 (m, 2H), 2.71-2.59 (m, 2H), 2.29-2.19
(m, 2H), 1.11 (s, 3H), 1.04 (s, 3H); 13C NMR (CDCl3,
100 MHz) d 196.2, 171.3, 167.3, 163.9, 151.7, 140.5, 137.5,
13
1.13 (s, 3H), 1.04 (s, 3H). C NMR (CDCl3, 100 MHz)
d 196.0, 170.8, 167.0, 164.4, 150.0, 147.4, 137.9, 129.1,
124.1, 112.6, 111.5, 60.6, 50.3, 40.9, 38.4, 32.3, 28.9, 27.5.
*e-mail: wliq870@163.com

S2
Alum-Catalyzed One-Pot Synthesis of Dihydropyrano[3,2-b]chromenediones
J. Braz. Chem. Soc.
MS (ESI): m/z 398 [M+H]+. Anal. calc. for C21H19NO7:
C 63.47, H 482, N 3.52; found: C 63.35, H 4.850, N 3.57.
4.81 (s, 1H), 4.45-4.37 (m, 2H), 3.80 (s, 6H), 3.79 (s, 3H),
2.68-2.63 (m, 2H), 2.28-2.27 (m, 2H), 1.14 (s, 3H), 1.11 (s,
3H). 13C NMR (CDCl3, 100 MHz) d 196.3, 171.3, 167.7,
164.0, 153.4, 151.5, 137.3, 136.1, 112.1, 105.0, 60.8, 60.6,
56.1, 50.3, 40.9, 38.5, 32.2, 29.3, 27.1; MS (ESI): m/z 443
[M+H]+. Anal. calc. for C24H26O8: C 65.15, H 5.92; found:
C 65.20, H 5.89.
2-(Hydroxymethyl)-7,7-dimethyl-10-(3-nitrophenyl)-7,8-
dihydropyrano[3,2-b]chromene-4,9(6H,10H)-dione (4e)
IR (KBr) νmax/cm-1: 3393, 2955, 2922, 2851, 1669,
1637, 1599, 1530, 1448, 1377, 1350, 1213, 1143, 1080,
678. 1H NMR (CDCl3, 400 MHz) d 8.11-8.09 (m, 2H), 7.63
(d, 1H, J 8.0 Hz), 7.50 (t, 1H, J 8.0 Hz), 6.53 (s, 1H), 5.03
(s, 1H), 4.45-4.33 (m, 2H), 274-2.61 (m, 2H), 2.30-2.20
(m, 2H), 1.12 (s, 3H), 1.05 (s, 3H). 13C NMR (CDCl3,
100 MHz) d 196.3, 171.3, 168.2, 164.7, 150.2, 148.4, 142.4,
137.7, 134.3, 129.8, 123.4, 122.9, 112.2, 111.3, 60.4, 50.3,
40.8, 38.3, 32.3, 28.9, 27.5. MS (ESI): m/z 398 [M+H]+.
Anal. calc. for C21H19NO7: C 63.47, H 482, N 3.52; found:
C 63.39, H 4.80, N 3.55.
2-(Hydroxymethyl)-7,7-dimethyl-10-(2,5-dimethoxy-
phenyl)-7,8-dihydropyrano[3,2-b]chromene- 4,9(6H,
10H)-dione (4i)
IR (KBr) νmax/cm-1: 3284, 2950, 2930, 2854, 1672, 1636,
1594, 1503, 1449, 1379, 1226, 1194, 1148, 1080, 1047,
1
819, 709; H NMR (CDCl3, 400 MHz) d 6.77-6.74 (m,
3H), 6.47 (s, 1H), 5.17 (s, 1H), 4.40-4.35 (m, 2H), 3.78 (s,
3H), 3.72 (s, 3H), 2.63-2.61 (m, 2H), 2.24-2.20 (m, 2H),
13
1.11 (s, 3H), 1.04 (s, 3H); C NMR (CDCl3, 100 MHz)
2-(Hydroxymethyl)-7,7-dimethyl-10-(2-chlorophenyl)-7,8-
dihydropyrano[3,2-b]chromene-4,9(6H,10H)-dione (4f)
IR (KBr) νmax/cm-1: 3291, 2956, 2931, 2860, 1673,
1634, 1600, 1468, 1445, 1378, 1221, 1116, 1080, 758.
1H NMR (CDCl3, 400 MHz) d 7.36 (dd, 1H, J 0.8, 8.0 Hz),
7.20-7.16 (m, 3H), 6.49 (s, 1H), 5.44 (s, 1H), 4.40-4.34 (m,
2H), 2.67-2.64 (m, 2H), 2.26-2.22 (m, 2H), 1.12 (s, 3H),
1.08 (s, 3H). 13C NMR (CDCl3, 100 MHz) d 196.1, 171.3,
168.0, 164.7, 150.9, 137.8, 137.5, 133.7, 130.1, 129.0,
127.3, 112.0, 111.5, 60.4, 50.3, 40.8, 35.7, 32.2, 29.0, 27.5;
MS (ESI): m/z 387 [M+H]+. Anal. calc. for C21H19ClO5:
C 65.20, H 4.95; found: C 65.30, H 4.82.
d 196.3, 171.3, 167.3, 164.6, 153.7, 151.7, 151.6, 137.8,
129.4, 116.1, 113.4, 112.7, 112.1, 111.4, 60.6, 56.6, 55.6,
50.4, 40.9, 33.8, 32.2, 29.2, 27.1; MS (ESI): m/z 413
[M+H]+. Anal. calc. for C23H24O7: C 66.98, H 5.87; found:
C 67.05, H 5.80.
2-(Hydroxymethyl)-7,7-dimethyl-10-(4-methylphenyl)-7,8-
dihydropyrano[3,2-b]chromene-4,9(6H,10H)-dione (4j)
IR (KBr) νmax/cm-1: 3368, 2953, 2931, 2847, 1668,
1636, 1442, 1376, 1219, 1189, 1120, 1076, 950, 862, 624.
1H NMR (CDCl3, 400 MHz) d 7.13 (d, 2H, J 8.0 Hz), 7.08
(d, 2H, J 8.0 Hz), 6.50 (s, 1H), 4.83 (s, 1H), 4.38-4.34 (m,
2H), 2.64-2.61 (m, 2H), 2.28 (s, 3H), 2.23-2.20 (m, 2H),
13
2-(Hydroxymethyl)-7,7-dimethyl-10-(2,4-dichlorophenyl)-
7,8-dihydropyrano[3,2-b]chromene-4,9(6H,10H)-dione
(4g)
1.10 (s, 3H), 1.03 (s, 3H); C NMR (CDCl3, 100 MHz)
d 196.4, 171.5, 168.2, 163.9, 152.0, 137.6, 137.5, 137.3,
129.5, 127.9, 112.4, 111.9, 60.4, 50.4, 40.8, 37.9, 32.2,
29.0, 27.4, 21.1; MS (ESI): m/z 367 [M+H]+. Anal. calc.
for C22H22O5:C 72.12, H 6.05; found: C 72.20, H 6.00.
IR (KBr) νmax/cm-1: 3296, 2952, 2863, 1676, 1637,
1600, 1445, 1376, 1221, 1101, 1079, 854. 1H NMR (CDCl3,
400 MHz) d 7.39 (s, 1H), 7.21-7.18 (m, 1H), 7.14-7.12
(m, 1H), 6.50 (s, 1H), 5.39 (s, 1H), 4.41-4.37 (m, 2H),
2.71-2.65 (m, 2H), 2.26-2.22 (m, 2H), 1.13 (s, 3H), 1.08 (s,
3H). 13C NMR (CDCl3, 100 MHz) d 196.0, 171.1, 167.6,
164.8, 150.3, 137.7, 134.4, 134.2, 130.9, 129.9, 127.7,
112.2, 111.2, 60.5, 50.3, 40.8, 37.5, 32.2, 28.9, 27.6. MS
(ESI): m/z 422 [M+H]+.Anal. calc. for C21H18Cl2O5: C 59.87,
H 4.31; found: C 59.90, H 4.28.
2-(Hydroxymethyl)-7,7-dimethyl-10-(4-methoxyphenyl)-
7,8-dihydropyrano[3,2-b]chromene-4,9(6H,10H)-dione
(4k)
IR (KBr) νmax/cm-1: 3355, 2958, 2922, 2836, 1672, 1637,
1511, 1443, 1377, 1219, 1193, 1120, 1029, 950, 860, 629;
1H NMR (CDCl3, 400 MHz) d 7.18-7.16 (m, 2H), 6.83-6.80
(m, 2H), 6.50 (s, 1H), 4.83 (s, 1H), 4.40-4.35 (m, 2H), 3.75
(s, 3H), 2.65-2.61 (m, 2H), 2.23-2.22 (m, 2H), 1.10 (s, 3H),
1.04 (s, 3H); 13C NMR (CDCl3, 100 MHz) d 196.4, 171.5,
168.0, 16.7, 159.0, 152.0, 137.3, 132.7, 129.1, 114.2, 112.5,
129.1, 60.5, 55.2, 50.4, 40.8, 37.5, 32.2, 29.0, 27.4; MS
(ESI): m/z 383 [M+H]+. Anal. calc. for C22H22O6:C 69.10,
H 5.80; found: C 69.20, H5.72.
2-(Hydroxymethyl)-7, 7-dimethyl-10-(3, 4, 5-
trimethoxyphenyl)-7,8-dihydropyrano[3,2-b]chromene-
4,9(6H, 10H)-dione (4h)
IR (KBr) νmax/cm-1: 3296, 2960, 2923, 2869, 1673,
1637, 1598, 1508, 1422, 1375, 1329, 1220, 1126, 1076,
1
956. H NMR (CDCl3, 400 MHz) d 6.50-6.44 (m, 3H),

Vol. 22, No. 11, 2011
Li et al.
S3
Figure S1. (A) 1H NMR of 4a (400 MHz, CDCl3). (B) 13C NMR of 4a (100 MHz, CDCl3). (C) IR of 4a.

S4
Alum-Catalyzed One-Pot Synthesis of Dihydropyrano[3,2-b]chromenediones
J. Braz. Chem. Soc.
Figure S2. (A) 1H NMR of 4b (400 MHz, CDCl3). (B) 13C NMR of 4b (100 MHz, CDCl3). (C) IR of 4b.

Vol. 22, No. 11, 2011
Li et al.
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Figure S3. (A) 1H NMR of 4c (400 MHz, CDCl3). (B) 13C NMR of 4c (100 MHz, CDCl3). (C) IR of 4c.

S6
Alum-Catalyzed One-Pot Synthesis of Dihydropyrano[3,2-b]chromenediones
J. Braz. Chem. Soc.
Figure S4. (A) 1H NMR of 4d (400 MHz, CDCl3). (B) 13C NMR of 4d (100 MHz, CDCl3). (C) IR of 4d.

Vol. 22, No. 11, 2011
Li et al.
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Figure S5. (A) 1H NMR of 4e (400 MHz, CDCl3). (B) 13C NMR of 4e (100 MHz, CDCl3). (C) IR of 4e.

S8
Alum-Catalyzed One-Pot Synthesis of Dihydropyrano[3,2-b]chromenediones
J. Braz. Chem. Soc.
Figure S6. (A) 1H NMR of 4f (400 MHz, CDCl3). (B) 13C NMR of 4f (100 MHz, CDCl3). (C) IR of 4f.

Vol. 22, No. 11, 2011
Li et al.
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Figure S7. (A) 1H NMR of 4g (400 MHz, CDCl3). (B) 13C NMR of 4g (100 MHz, CDCl3). (C) IR of 4g.

S10
Alum-Catalyzed One-Pot Synthesis of Dihydropyrano[3,2-b]chromenediones
J. Braz. Chem. Soc.
Figure S8. (A) 1H NMR of 4h (400 MHz, CDCl3). (B) 13C NMR of 4h (100 MHz, CDCl3). (C) IR of 4h.

Vol. 22, No. 11, 2011
Li et al.
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Figure S9. (A) 1H NMR of 4i (400 MHz, CDCl3). (B) 13C NMR of 4i (100 MHz, CDCl3). (C) IR of 4i.

S12
Alum-Catalyzed One-Pot Synthesis of Dihydropyrano[3,2-b]chromenediones
J. Braz. Chem. Soc.
Figure S10. (A) 1H NMR of 4j (400 MHz, CDCl3). (B) 13C NMR of 4j (100 MHz, CDCl3). (C) IR of 4j.

Vol. 22, No. 11, 2011
Li et al.
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Figure S11. (A) 1H NMR of 4k (400 MHz, CDCl3). (B) 13C NMR of 4k (100 MHz, CDCl3). (C) IR of 4k.