CeCl3·7H2O as mild and efficient catalyst for the one-pot multicomponent synthesis of 8-aryl-7,8-dihydro[1,3]dioxolo[4,5-g] chromen-6-ones

Article abstract of DOI:10.1135/cccc2010139

A series of new 8-aryl-7,8-dihydro[1,3]dioxolo[4,5-g]chromen-6-ones were synthesized via a three-component reaction of 3,4-methylenedioxyphenol, aromatic aldehydes and Meldrum's acid in the presence of CeCl₃·7H ₂O under solvent-free

Full text of DOI:10.1135/cccc2010139

Synthesis of [1,3]Dioxolo[4,5-g]chromen-6-ones
235
CeCl3·7H2O AS MILD AND EFFICIENT CATALYST FOR
THE ONE-POT MULTICOMPONENT SYNTHESIS OF
8-ARYL-7,8-DIHYDRO[1,3]DIOXOLO[4,5-g]CHROMEN-6-ONES
1,
2
3
Li-Qiang WU *, Wei-Lin LI and Fu-Lin YAN
School of Pharmacy, Xinxiang Medical University, Xinxiang, Henan 453003, P. R. China;
1
2
3
e-mail: wliq870@163.com, linweilin1977@163.com, yannz2009@163.com
Received November 22, 2010
Accepted February 2, 2011
Published online March 3, 2011
A series of new 8-aryl-7,8-dihydro[1,3]dioxolo[4,5-g]chromen-6-ones were synthesized
via a three-component reaction of 3,4-methylenedioxyphenol, aromatic aldehydes and
Meldrum’s acid in the presence of CeCl3·7H2O under solvent-free conditions. The method
provided several advantages such as easy work-up, high yields and environmentally benign
procedure.
Keywords: [1,3]Dioxolo[4,5-g]chromen-6-one; Meldrum’s acid; CeCl3·7H2O; Solvent-free.
Multi-component, one-pot synthesis has received considerable attention
because of their wide range of applications in pharmaceutical chemistry for
creation of structural diversity and combinatorial libraries for drug discov-
ery1. MCRs are extremely convergent, producing a remarkably high increase
of molecular complexity in just one step2. The ready availability, potential
biological activity and high reactivity of 2-chromanone makes it attractive
molecule in pharmaceutical chemistry3. Consequently, a large number of
3,4-methylenedioxyphenol derivatives have been prepared for biological
evaluation4.
CeCl3·7H2O is a relatively cheap, water and air stable, and non-toxic re-
agent5. Due to the hardness of the cerium cation, it is able to activate car-
bonyl functionalities for nucleophilic attack and has been used as a Lewis
acid for several transformations6. Herein, we report a mild and efficient
protocol for the preparation of 8-aryl-7,8-dihydro[1,3]dioxolo[4,5-g]-
chromen-6-ones by three-component reactions of an aromatic aldehyde,
3,4-methylenedioxyphenol and Meldrum’s acid catalyzed by CeCl3·7H2O at
110 °C under solvent-free conditions (Scheme 1).
Collect. Czech. Chem. Commun. 2011, Vol. 76, No. 4, pp. 235–241
© 2011 Institute of Organic Chemistry and Biochemistry
doi:10.1135/cccc2010139

236
Wu, Li, Yan:
Ar
O
O
O
CeCl3 7 H2O
neat, 110 oC
O
O
O
ArCH2O
+
+
O
O
O
O
OH
1
2
3
4
SCHEME 1
RESULTS AND DISCUSSION
Initially, we conducted the reaction of 3,4-methylenedioxyphenol,
benzaldehyde and Meldrum’s acid in the presence of various metal halides
such as LiBr, FeCl3, ZnCl2, InBr3 and CeCl3·7H2O separately at 110 °C under
solvent-free conditions. The corresponding 8-phenyl-7,8-dihydro[1,3]di-
oxolo[4,5-g]chromen-6-one was formed in 42, 35, 65, 72 and 88% yield, re-
spectively (Table I). When reactions were carried out in the absence of
a catalyst for long period of time (4–6 h), yield of the product was low.
CeCl3·7H2O was thus selected as the most effective catalyst to carry out this
reaction.
Next, to optimize the amount of the catalyst and the reaction tem-
perature, the reaction of 3,4-methylenedioxyphenol, benzaldehyde and
Meldrum’s acid was studied under solvent-free conditions in the presence
of CeCl3·7H2O at different temperatures. The results are summarized in
Table II, and show that the reaction using 10 mole % CeCl3·7H2O at 110 °C
proceeded in the highest yield.
TABLE I
Synthesis of 8-phenyl-7,8-dihydro[1,3]dioxolo[4,5-g]chromen-6-one using metal halidesa
Entry
Metal halide
Time, h
Yield, %b
1
2
3
4
5
6
–
6
4
5
3
2
2
0
42
35
65
72
88
LiBr
FeCl3
ZnCl2
InBr3
CeCl3·7H2O
a
Reaction conditions: 3,4-methylenedioxyphenol (1 mmol), benzaldehyde (1 mmol),
b
Meldrum’s acid (1 mmol), metal halides (0.1 mmol); neat, 110 °C. Isolated yield.
Collect. Czech. Chem. Commun. 2011, Vol. 76, No. 4, pp. 235–241

Synthesis of [1,3]Dioxolo[4,5-g]chromen-6-ones
237
TABLE II
Synthesis of 8-phenyl-7,8-dihydro[1,3]dioxolo[4,5-g]chromen-6-one under various condi-
tionsa
Entry
CeCl3·7H2O, mole %
Temperature, °C
Time, h
Yield, %b
1
2
0
1
110
110
110
110
25
6
0
48
56
67
0
4
3
2
4
4
5
3
5
10
10
10
10
10
10
10
15
15
20
25
6
6
50
6
28
65
76
88
88
87
82
88
87
86
7
90
4
8
100
110
120
130
100
110
110
110
3
9
2
10
11
12
13
14
15
2
2
2
1.5
1.5
1.5
a
Reaction conditions: 3,4-methylenedioxyphenol (1 mmol), benzaldehyde (1 mmol),
b
Meldrum’s acid (1 mmol); neat. Isolated yield.
TABLE III
Preparation of 8-aryl-7,8-dihydro[1,3]dioxolo[4,5-g]chromen-6-onesa
Entry
Ar
Time, h
Product
Yield, %b
1
2
C6H5
2
4a
4b
4c
4d
4e
4f
88
92
86
82
92
85
88
85
86
87
4-Cl-C6H4
1.5
1.5
3
3
4-F-C6H4
4
4-Me-C6H4
4-NO2-C6H4
3-NO2-C6H4
2,4-diCl-C6H3
4-MeO-C6H4
2,5-diMeO-C6H3
2-Cl-C6H4
5
1.5
2
6
7
2.5
3.5
3.5
2
4g
4h
4i
8
9
10
4j
a
Reaction conditions: 3,4-methylenedioxyphenol (1 mmol), aldehyde (1 mmol), Meldrum’s
b
acid (1 mmol), CeCl3·7H2O (0.1 mmol); neat, 110 °C. Isolated yield.
Collect. Czech. Chem. Commun. 2011, Vol. 76, No. 4, pp. 235–241

238
Wu, Li, Yan:
With this optimized procedure in hand, the scope of application of
this three-component reaction was examined using different aldehydes
as starting materials. As seen from Table III, aromatic aldehydes having
electron-donating as well as electron-withdrawing groups were uniformly
transformed into the corresponding 8-aryl-7,8-dihydro[1,3]dioxolo[4,5-g]-
chromen-6-ones in high to excellent yields within 3.5 h. Substituents on
the aromatic ring had no obvious effect on yield or reaction time under the
above mentioned optimal conditions (Table III). All of the products 4 ex-
1
hibited a triplet in their H NMR spectra at δ 4.08–4.74 ppm for H-8, two
doublets at δ 5.94–5.99 ppm for –OCH2O–, two singlets at δ 6.38–6.69 ppm
for H-4,9. A distinguishing peak at δ 37.0–40.6 ppm for C-8 in their
13C NMR spectra, a distinguishing peak at δ 166.4–168.0 ppm carbonyl
group and a distinguishing peak at δ 99.1–99.5 ppm for –OCH2O– have
been observed.
CeCl3
O
O
O
O
H
CeCl3
O
O
Ar
O
O
Ar
OH
-CeCl3-OH
CeCl3
R
H
O
O
R
H
5
O
O
2
O
HO
3
O
Ar
O
O
Ar
O
O
O
OH
-CO2
-(CH3)2CO
O
O
O
1
O
O
O
O
O
OH
O
7
6
Ar
O
O
O
O
4
SCHEME 2
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Synthesis of [1,3]Dioxolo[4,5-g]chromen-6-ones
239
The formation of products 4a–4i can be rationalized by initial formation
of heterodiene 5 by standard Knoevenagel condensation of 2-hydroxy-
naphthalene-1,4-dione 3 and aromatic aldehyde 2 in the presence of a cata-
lytic amount of CeCl3·7H2O. Subsequent Michael-type addition of 3,4-
methylenedioxyphenol 1 to the heterodienes 5 followed by cyclization,
dehydration and air oxidation affords the corresponding products 4a–4j
(Scheme 2).
CONCLUSION
In conclusion, we have developed a highly efficient methodology for a
three-component reaction of 3,4-methylenedioxyphenol, aromatic alde-
hydes and Meldrum’s acid catalyzed by safe CeCl3·7H2O, furnishing a class
of 8-aryl-7,8-dihydro[1,3]dioxolo[4,5-g]chromen-6-ones in high yield. This
method is advantageous in terms of simplicity and mildness, and hopefully
could Þnd wide application in synthesis of complex chromene-containing
compounds.
EXPERIMENTAL
1H and 13C NMR spectra were determined on a Bruker AV-400 spectrometer (100 MHz for
13C NMR) at room temperature using tetramethylsilane (TMS) as an internal standard
(CDCl3 solution). Chemical shifts are given in ppm (δ-scale), coupling constants (J) in Hz. IR
spectra were determined on a FTS-40 infrared spectrometer. Elemental analysis were per-
formed by a Vario-III elemental analyzer. Mass spectra were taken on a Macro mass spec-
trometer (Waters) by electro-spray method (ES). Melting points were determined on a XT-4
binocular microscope and were uncorrected. Commercially available reagents were used
without further purification unless otherwise stated.
General Procedure for Preparation of 4
A mixture of 3,4-methylenedioxyphenol (1 mmol), aldehyde (1 mmol), Meldrum’s acid
(1 mmol) and CeCl3·7H2O (0.1 mmol) were heated at 110 °C for an appropriate time (TLC).
After completion, the reaction mixture was washed with water (15 ml), and the crude prod-
uct purified by silica gel column chromatography using CH2Cl2 as an eluent to afford the
pure product 4.
8-Phenyl-7,8-dihydro[1,3]dioxolo[4,5-g]chromen-6-one (4a). White powder, m.p. 133–134 °C.
1H NMR: 7.37–7.26 (m, 3 H), 7.16–7.14 (m, 2 H) 6.68 (s, 1 H), 6.39 (s, 1 H), 5.95 (d, 1 H, J =
1.2), 5.94 (d, 1 H, J = 1.2), 4.22 (t, J = 7.2, 1 H), 3.07–2.93 (m, 2 H). 13C NMR: 167.7, 147.5,
146.2, 144.4, 140.4, 129.2, 128.6, 127.7, 127.5, 117.9, 107.3, 101.7, 99.1, 40.6, 37.0. MS
(ESI): m/z 269 [M + H]+. For C16H12O4 (268.27) calculated: 71.64% C, 4.51% H; found:
71.60% C, 4.36% H.
8-(4-Chlorophenyl)-7,8-dihydro[1,3]dioxolo[4,5-g]chromen-6-one (4b). White powder, m.p.
205–206 °C. 1H NMR: 7.32 (d, 2 H, J = 8.4), 7.08 (d, 2 H, J = 8.4), 6.66 (s, 1 H), 6.38 (s, 1 H),
5.97 (d, 1 H, J = 0.8), 5.96 (d, 1 H, J = 0.8), 4.21 (t, J = 6.8, 1 H), 3.06–2.89 (m, 2 H).
Collect. Czech. Chem. Commun. 2011, Vol. 76, No. 4, pp. 235–241

240
Wu, Li, Yan:
13C NMR: 167.8, 148.1, 146.7, 144.8, 136.4, 134.2, 134.1, 130.0, 129.4, 127.9, 115.7, 107.1,
101.9, 99.3, 37.0, 35.3. MS (ESI): m/z 303 [M + H]+. For C16H11ClO4 (302.72) calculated:
63.48% C, 3.66% H; found: 63.39% C, 3.71% H.
8-(4-Fluorophenyl)-7,8-dihydro[1,3]dioxolo[4,5-g]chromen-6-one (4c). White semi-solid.
1H NMR: 7.13–7.09 (m, 2 H), 7.05–7.01 (m, 2 H), 6.66 (s, 1 H), 6.38 (s, 1 H), 5.96 (d, 2 H, J =
1.2), 4.22 (t, J = 6.8, 1 H), 3.06–2.89 (m, 2 H). 13C NMR: 167.3, 147.7, 146.2, 144.5, 136.2,
136.1, 129.1, 129.0, 117.6, 116.2, 116.0, 107.1, 101.8, 99.2, 39.9, 37.2. MS (ESI): m/z 287
[M + H]+. For C16H11FO4 (286.26) calculated: 67.13% C, 3.87% H; found: 67.09% C, 3.92% H.
8-(4-Methylphenyl)-7,8-dihydro[1,3]dioxolo[4,5-g]chromen-6-one (4d). White powder, m.p.
143–144 °C. 1H NMR: 7.15 (d, 2 H, J = 7.6), 7.03 (d, 2 H, J = 8.0), 6.65 (s, 1 H), 6.39 (s, 1 H),
5.95 (d, 1 H, J = 1.2), 5.94 (d, 1 H, J = 1.2), 4.08 (t, J = 7.6, 1 H), 3.05–2.91 (m, 2 H), 2.34 (s,
3 H). 13C NMR: 167.7, 147.4, 146.1, 144.4, 137.4, 129.8, 127.3, 118.2, 107.3, 101.7, 99.1,
40.2, 37.0, 31.0. MS (ESI): m/z 283 [M + H]+. For C17H14O4 (282.30) calculated: 72.33% C,
5.00% H; found: 72.40% C, 4.97% H.
8-(4-Nitrophenyl)-7,8-dihydro[1,3]dioxolo[4,5-g]chromen-6-one (4e). White powder, m.p.
225–226 °C. 1H NMR: 8.21 (d, 2 H, J = 8.8), 7.33 (d, 2 H, J = 8.8), 6.69 (s, 1 H), 6.40 (s, 1 H),
5.99 (d, 1 H, J = 1.2), 5.98 (d, 1 H, J = 1.2), 4.30 (t, J = 6.0, 1 H), 3.14–2.95 (m, 2 H).
13C NMR: 166.4, 148.2, 147.9, 147.4, 146.3, 144.8, 128.4, 124.4, 115.8, 107.0, 102.0, 99.5,
40.5, 36.7. MS (ESI): m/z 314 [M + H]+. For C16H11NO6 (313.27) calculated: 61.35% C,
3.54% H, 4.47% N; found: 61.28% C, 3.60% H, 4.52% N.
8-(3-Nitrophenyl)-7,8-dihydro[1,3]dioxolo[4,5-g]chromen-6-one (4f). White powder, m.p.
142–143 °C. 1H NMR: 8.17–8.15 (m, 1 H), 8.03 (s, 1 H), 7.56–7.46 (m, 2 H), 6.69 (s, 1 H),
6.40 (s, 1 H), 5.99 (d, 2 H, J = 0.8), 4.37 (t, J = 6.4, 1 H), 3.14–2.97 (m, 2 H). 13C NMR:
166.6, 148.7, 148.2, 146.3, 144.8, 142.7, 133.5, 130.3, 122.9, 122.6, 115.9, 107.0, 102.0,
99.5, 40.4, 36.9. MS (ESI): m/z 314 [M + H]+. For C16H11NO6 (313.27) calculated: 61.35% C,
3.54% H, 4.47% N; found: 61.33% C, 3.59% H, 4.49% N.
8-(2,4-Dichlorophenyl)-7,8-dihydro[1,3]dioxolo[4,5-g]chromen-6-one (4g). White powder, m.p.
179–180 °C. 1H NMR: 7.45 (d, 1 H, J = 2.0), 7.16 (dd, 1 H, J = 2.0, 8.4), 6.81 (d, 1 H, J = 8.4),
6.69 (s, 1 H), 6.44 (s, 1 H), 5.98 (d, 2 H, J = 1.2), 4.68 (t, J = 6.0, 1 H), 3.02–2.97 (m, 2 H).
13C NMR: 166.5, 148.7, 148.2, 146.3, 144.8, 142.7, 136.4, 133.5, 130.3, 122.6, 115.7, 106.9,
101.9, 99.3, 40.4, 36.9. MS (ESI): m/z 337 [M + H]+. For C16H10Cl2O4 (337.16) calculated:
57.00% C, 2.99% H; found: 57.03% C, 3.02% H.
8-(4-Methoxyphenyl)-7,8-dihydro[1,3]dioxolo[4,5-g]chromen-6-one (4h). White powder, m.p.
129–130 °C. 1H NMR: 7.06 (d, 2 H, J = 8.8), 6.87 (d, 2 H, J = 8.8), 6.65 (s, 1 H), 6.40 (s, 1 H),
5.95 (d, 2 H, J = 1.2), 4.17 (t, J = 6.0, 1 H), 3.80 (s, 3 H), 3.00–2.93 (m, 2 H). 13C NMR:
167.8, 159.0, 147.4, 146.1, 144.4, 132.3, 128.5, 118.4, 114.5, 107.2, 101.7, 99.1, 55.3, 39.8,
37.2. MS (ESI): m/z 299 [M + H]+. For C17H14O5 (298.30) calculated: 68.45% C, 4.73% H;
found: 68.51% C, 4.77% H.
8-(2,5-Dimethoxyphenyl)-7,8-dihydro[1,3]dioxolo[4,5-g]chromen-6-one (4i). White powder,
m.p. 121–122 °C. 1H NMR: 6.82 (d, 1 H, J = 8.8), 6.76 (d, 1 H, J = 3.2), 6.64 (s, 1 H), 6.46 (s,
1 H), 6.43 (d, 1 H, J = 3.2), 5.95 (d, 1 H, J = 1.2), 5.94 (d, 1 H, J = 1.2), 4.51 (t, J = 6.0, 1 H),
3.79 (s, 3 H), 3.69 (s, 3 H), 3.03–2.95 (m, 2 H). 13C NMR: 168.0, 153.6, 150.9, 147.4, 146.5,
144.4, 129.9, 116.8, 115.2, 112.1, 116.7, 107.3, 101.6, 99.0, 55.6, 55.6, 35.4, 35.0. MS (ESI):
m/z 329 [M + H]+. For C18H16O6 (328.32) calculated: 65.85% C, 4.91% H; found: 65.88% C,
4.87% H.
8-(Chorophenyl)-7,8-dihydro[1,3]dioxolo[4,5-g]chromen-6-one (4j). White powder, m.p.
160–161 °C. 1H NMR: 7.43 (dd, 1 H, J = 0.8, 7.6), 7.25–7.17 (m, 2 H), 6.88 (dd, 1 H, J = 0.8,
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Synthesis of [1,3]Dioxolo[4,5-g]chromen-6-ones
241
7.2), 6.69 (s, 1 H), 6.45 (s, 1 H), 5.98 (d, 1 H, J = 1.2), 5.97 (d, 1 H, J = 1.2), 4.74 (t, J = 6.4,
1 H), 3.05–3.02 (m, 2 H). 13C NMR: 167.2, 147.8, 146.7, 144.7, 137.7, 133.4, 130.1, 129.0,
128.5, 127.6, 116.3, 107.2, 101.8, 99.2, 37.3, 35.4. MS (ESI): m/z 303 [M + H]+. For
C
16H11ClO4 (302.72) calculated: 63.48% C, 3.66% H; found: 63.44% C, 3.70% H.
We are pleased to acknowledge the financial support from Xinxiang Medical University.
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