Synthesis of functionalized chromenes from Meldrum's acid, 4-hydroxycoumarin, and ketones or aldehydes

Article abstract of DOI:10.2174/138620710792927358

An efficient synthesis of 4-alkyl-4-methyl-3,4-dihydro-2H,5H-pyrano[3,2-c] chromene-2,5-dione or 4-aryl-3,4- dihydro-2H,5H-pyrano[3,2-c]chromene-2,5-diones via reaction 4-hydroxycoumarin with Meldrum's acid and ketones or aldehydes is described.

Full text of DOI:10.2174/138620710792927358

Combinatorial Chemistry & High Throughput Screening, 2010, 13, 813-817
813
Synthesis of Functionalized Chromenes from Meldrum’s Acid, 4-
Hydroxycoumarin, and Ketones or Aldehydes
Maryam Sabbaghan*,1, Issa Yavari2 and Zinatossadat Hossaini3
1Faculty of Sciences, Chemistry Department, Shahid Rajaee Teacher Training University, P.O. Box 16785-163, Tehran,
Iran
2Department of Chemistry, Tarbiat Modares University, P.O. Box 14115-175, Tehran, Iran
3Chemistry Department, Islamic Azad University, Qaemshahr Branch, PO Box 163 Mazandaran, Iran
Abstract: An efficient synthesis of 4-alkyl-4-methyl-3,4-dihydro-2H,5H-pyrano[3,2-c]chromene-2,5-dione or 4-aryl-3,4-
dihydro-2H,5H-pyrano[3,2-c]chromene-2,5-diones via reaction 4-hydroxycoumarin with Meldrum’s acid and ketones or
aldehydes is described.
Keywords: Chromene, proline, aqueous media, meldrum’s acid, 4-hydroxycoumarin.
1
1. INTRODUCTION
Structures of compounds 4a–4e were assigned by IR, H
NMR, 13C NMR and mass spectral data. The 1H NMR
spectrum of 4a showed two singlets arising from methyl and
Chromenes have attracted considerable attention due to
their biological activity and their presence in a variety of
significant natural products [1]. Pyrano[3,2-c]chromene
derivatives are a class of important heterocycles with a wide
range of biological properties [2] such as spasmolytic,
diuretic, anticoagulant, anti-cancer, and anti-anaphylactic
activity [3]. Moreover they can be used as cognitive
enhancers, for the treatment of neurodegenerative diseases,
including Alzheimer’s disease, amyotrophic lateral sclerosis,
Parkinson’s disease, Huntington’s disease, AIDS associated
dementia and Down’s syndrome as well as for the treatment
of schizophrenia and myoclonus [4].
1
methylene protons, along with the aromatic protons. The H
NMR spectrum of 4b-4e exhibited a characteristic AB
system for the CH2 moiety. The carbonyl group resonances
in the 13C NMR spectrum of 4a appear at 159.5 and 164.8
ppm. The mass spectrum of 4a displayed the molecular ion
peak at m/z = 244.
Although the mechanistic details of the reaction are not
known, a plausible rationalization may be advanced to
explain the product formation (Scheme 2). It is conceivable
that the initial event is the formation of 5 which undergoes
Knoevenagel condensation with Meldrum’s acid followed by
addition of 4-hydroxycoumarin to generate intermediate 6.
This intermediate undergoes first loses acetone to afford
ketene 7, which undergoes cyclization and decarboxylation
to produce product 4.
Consequently, a number of synthetic strategies for the
construction pyrano[3,2-c]chromene derivatives have been
reported [5]. Some of the reported procedures require long
reaction times, multi-step reactions and complex synthetic
pathways, affording products with only modest yields [6-13].
Therefore, the development of more effective methods for
their preparation is still necessary. Herein, we describe very
simple and efficient route to the synthesis of 4-alkyl-4-
methyl-3,4-dihydro-2H,5H-pyrano[3,2-c]chromene-2,5-dione
using excess ketones, Meldrum’s acid and 4-hydroxy-
coumarin at room temperature.
The reaction of 4-hydroxycoumarin 1 with Meldrum’s
acid 2 and benzaldehydes 9 in 50% aqueous EtOH in the
presence of proline (10 mol %) led to 4-aryl-3,4-dihydro-
2H,5H-pyrano[3,2-c]chromene-2,5-diones 10 in good yields
(Scheme 3) [16].
Structures of compounds 10a–10g were assigned by IR,
1H NMR, 13C NMR and mass spectral data. For example, the
1H NMR spectrum of 10a exhibited a characteristic ABM
system for the CH2-CH moiety. The resonances of the
carbonyl groups in the 13C NMR spectrum of 10a appear at
161.2 and 164.7 ppm. The mass spectrum of 10a displayed
2. RESULTS AND DISCUSSION
As part of our current studies [14, 15] on the development
of new routes to heterocyclic systems, we now report an
efficient synthetic route to functionalized chromenes. Thus
the reaction of 4-hydroxycoumarin 1 with Meldrum’s acid 2
and excess ketones 3 in the presence of piperidine at room
temperature led to 4-alkyl-4-methyl-3,4-dihydro-2H,5H-
pyrano[3,2-c]chromene-2,5-dione 4 in good yields (Scheme
1). Under similar conditions, we also used different bases for
this reaction that they didn’t lead to the product.
the molecular ion peak at m/z = 292. The H and 13C NMR
1
spectra of 10b-10g are similar to those of 10a except for the
benzene moieties, which show characteristic signals in the
appropriate regions of the spectra. A tentative mechanism for
this transformation is proposed in literature [16].
3. CONCLUSION
In conclusion, we have developed a convenient, one-pot
method for the synthesis of 4-aryl-3,4-dihydro-2H,5H-
pyrano[3,2-c]chromene-2,5-diones or 4-alkyl-4-methyl-3,4-
*Address correspondence to this author at the Faculty of Sciences,
Chemistry Department, Shahid Rajaee Teacher Training University, P.O.
Box 16785-163, Tehran, Iran; Fax: +98-21-22970033;
E-mails: sabbaghan@srttu.edu, msaba16us@yahoo.com
1386-2073/10 $55.00+.00
© 2010 Bentham Science Publishers Ltd.

814 Combinatorial Chemistry & High Throughput Screening, 2010, Vol. 13, No. 9
Sabbaghan et al.
O
O
O
OH
R
O
O
O
Pipiridine
Me
+
O
+
R
Me
O
O
O
O
1
2
3
R
4
Yield/%
97
Me
a
b
c
d
e
Et
87
78
65
50
nPr
Me2CHCH2
nPentyl
Scheme 1. Reaction of 4-hydroxycoumarin with Meldrum’s acid and ketones in the presence of piperidine at rt.
Scheme 2. Proposed mechanism for the reaction of 4-hydroxycoumarin with Meldrum’s acid and ketones in the presence of piperidine.
dihydro-2H,5H -pyrano[3,2-c]chromene-2,5-dione using 4-
hydroxycoumarin and Meldrum’s acid in the presence of
benzaldehydes or ketones. The functionalized chromenes
reported in this work may be considered as potentially useful
synthetic intermediates because they possess atoms with
different oxidation states. The advantage of the present
procedure is that the reaction is performed under neutral
conditions by simple mixing of the starting materials. The
simplicity of the present procedure makes it an interesting
alternative to other approaches.
(0.84 g, 2 mmol). The reaction mixture was stirred for 4 hours.
After completion of the reaction (monitored by TLC), was
added 4-hydroxycoumarin (0.32 g, 2 mmol). The reaction
mixture was stirred for 12 h. The solvent was removed under
reduced pressure, and the residue was purified by column
chromatography (SiO2; hexane/AcOEt) to afford 4.
4,4-Dimethyl-3,4-Dihydro-2H,5H-Pyrano[3,2-c]Chromene-
2,5-Dione (4a)
White powder, yield: 0.47 g (97%), m.p. 128-131°C. IR
1
(KBr) (ꢀmax/cmꢁ1): 1794, 1712, 1626, 1358 cm-1. H NMR:
4. MATERIAL AND METHODS
1.98 (s, 6 H, 2 Me), 3.23 (s, 2 H, CH2), 7.80 (t, 3J = 8.1 Hz, 1
3
3
H, CH), 7.81 (d, J = 7.6 Hz, 1 H, CH), 8.06 (td, J = 8.56
Mp: Electrothermal-9100 apparatus; uncorrected. IR
4
3
Hz, J = 1.15 Hz, 1 H, 1 CH), 7.81 (d, J = 7.8 Hz, 1 H,
CH).13C NMR: 26.5 (2 Me), 33.8 (C), 44.3 (CH2), 111.1 (C),
114.0 (C), 116.4 (CH), 123.1 (CH), 124.4 (CH), 132.6 (CH),
152.7 (C), 156.0 (C), 159.5 (C=O), 164.8 (C=O). EI-MS:
245 (M++1, 95), 244 (M+, 85), 229 (65), 216 (45), 201 (100),
121 (50), 92 (40). Anal. Calcd for C14H12O4 (244.24): C
68.85, H 4.95%. Found: C 68.10, H 5.01%.
1
Spectra: Shimadzu IR-460 spectrometer. H- and 13C-NMR
spectra: Bruker DRX-500 AVANCE instrument; in CDCl3 at
500.1 and 125.7 MHz, resp.; ꢀ in ppm, J in Hz. EI-MS (70
eV): Finnigan-MAT-8430 mass spectrometer, in m/z.
Elemental analyses (C, H, N) were performed with a Heraeus
CHN-O-Rapid analyzer. All chemicals were used as-
received from the appropriate suppliers.
4-Ethyl-4-Methyl-3,4-Dihydro-2H,5H-Pyrano[3,2-c]Chromene-
2,5-Dione (4b)
General Procedure
White powder, yield: 0.45 g (87%), m.p. 100-103 °C. IR
To a stirred solution of Meldrum’s acid (0.29 g, 2 mmol)
and methyl ketones as a solvent was added pipyridine
1
(KBr) (ꢀmax/cmꢁ1): 1796, 1716, 1624, 1377 cm-1. H NMR:

Synthesis of Functionalized Chromenes from Meldrum’s Acid
Combinatorial Chemistry & High Throughput Screening, 2010, Vol. 13, No. 9 815
O
O
Proline (10 mol%)
EtOH/H2O, Reflux
R
2
1
+
+
RCHO
O
O
9
10
9, 10
a
R
Yield/% of 10
C6H5
94
92
85
b
3-Br-C6H4
4-Me-C6H4
4-MeO-C6H4
4-Cl-C6H4
2-Cl-C6H4
2-Me-C6H4
c
d
e
83
78
75
81
f
g
88
84
h 1-Naphthyl
i
CO2Et
Scheme 3. The reaction of 4-hydroxycoumarin with Meldrum’s acid and benzaldehydes in 50% aqueous EtOH in the presence of proline (10
mol %).
1.33 (t, 3J = 7.5 Hz, 3 H, Me), 1.92 (s, 3 H, Me), 2.06 (dq, 2J
= 6.7 Hz, 3J = 7.4 Hz, 1 H, CH), 2.56 (dq, 2J = 6.7 Hz, 3J =
Me), 1.56 (s, 3 H, Me), 1.59 (dd, 2J = 5.3 Hz, 3J = 14.4 Hz, 1
2 3
H, CH), 1.70-1.75 (m, 1 H, CH), 2.04 (dd, J = 5.3 Hz, J =
14.4 Hz, 1 H, CH), 2.69 (d, 2J = 15.9 Hz, 1 H, CH), 2.96 (d,
2J = 15.8 Hz, 1 H, CH), 7.35-7.38 (m, 2 H, 2 CH), 7.62 (td,
3J = 7.37 Hz, 4J = 1.5 Hz, 1 H, 1 CH), 7.89 (dd, 3J = 7.9 Hz,
4J = 1.5 Hz, 1 H, CH). 13C NMR: 24.7 (Me), 25.3 (CH), 25.6
(Me), 26.7 (Me), 37.9 (C), 42.4 (CH2), 47.7 (CH2), 111.2
(C), 114.0 (C), 116.9 (CH), 123.5 (CH), 124.7 (CH), 133.0
(CH), 153.1 (C), 156.7 (C), 160.1 (C=O), 165.7 (C=O). EI-
MS: 287 (M++1, 80), 244 (M+, 68), 272 (65), 259 (45), 244
(100), 121 (50), 92 (30). Anal. Calcd for C17H18O4 (286.32):
C 71.31, H 6.34%. Found: C 71.0, H 6.22%.
2
7.4 Hz, 1 H, CH), 3.07 (d, J = 15.9 Hz, 1 H, CH), 3.30 (d,
2J = 15.9 Hz, 1 H, CH), 7.74-7.77 (m, 2 H, 2 CH), 8.02 (td,
4
3
3J = 7.35 Hz, J = 1.55 Hz, 1 H, 1 CH), 8.26 (dd, J = 8.1
Hz, 4J = 1.45 Hz, 1 H, CH).13C NMR: 8.90 (Me), 25.3 (Me),
31.7 (CH2), 37.6 (C), 40.9 (CH2), 109.6 (C), 113.6 (C), 116.3
(CH), 122.9 (CH), 124.3 (CH), 132.6 (CH), 152.7 (C), 156.8
(C), 159.5 (C=O), 165.3 (C=O). EI-MS: 259 (M++1, 95), 258
(M+, 85), 243 (74), 230 (42), 215 (100), 121 (44), 92 (42).
Anal. Calcd for C15H14O4 (258.27): C 69.76, H 5.46%.
Found: C 69.22, H 5.40%.
4-Methyl-4-Propyl-3,4-Dihydro-2H,5H-Pyrano[3,2-c]Chromene-
2,5-Dione (4c)
4-Methyl-4-Pentyl-3,4-Dihydro-2H,5H-Pyrano[3,2-c]Chromene-
2,5-Dione (4e)
White powder, yield: 0.42g (78%), m.p. 87-93°C. IR
Yellow oil, yield: 0.30g (50%), IR (KBr) (ꢀmax/cmꢁ1):
1
1
3
(KBr) (ꢀmax/cmꢁ1): 1794, 1710, 1622, 1358cm-1. H NMR:
1792, 1712, 1622, 1358 cm-1. H NMR: 1.35 (t, J = 6.9 Hz,
3 H, Me), 1.75 (s, 3 H, Me), 1.78-2.1 (m, 8 H, 4 CH2), 3.09
(d, 2J = 15.9 Hz, 1 H, CH), 2.91 (d, 2J = 15.9 Hz, 1 H, CH),
1.36 (t, 3J = 7.3 Hz, 3 H, Me), 1.64-1.79 (m, 2 H, CH2), 1.95
2
3
(s, 3 H, Me), 2.01 (dt, J = 4.4 Hz, J = 12.8 Hz, 1 H, CH),
2
3
2
3
2.48 (dt, J = 4.4 Hz, J = 12.8 Hz, 1 H, CH), 3.09 (d, J =
7.72-7.78 (m, 2 H, 2 CH), 7.96 (t, J = 7.3 Hz, 1 H, 1 CH),
2
3
15.9 Hz, 1 H, CH), 3.31 (d, J = 15.9 Hz, 1 H, CH), 7.75-
8.28 (d, J = 7.7 Hz, 1 H, CH).13C NMR: 14.3 (Me), 22.5
7.78 (m, 2 H, 2 CH), 8.02 (td, 3J = 8.8 Hz, 4J = 1.4 Hz, 1 H,
(CH2), 24.9 (Me), 29.3 (CH2), 31.4 (CH2), 32.7 (CH2), 36.7
(C), 46.7(CH2), 108.9 (C), 109.9 (C), 116.2 (CH), 122.7
(CH), 123.4 (CH), 130.9 (CH), 152.7 (C), 158.7(C), 159.6
(C=O), 162.3 (C=O). EI-MS: 301 (M++1, 80), 300 (M+, 68),
285 (65), 272 (45), 257 (100), 121 (50), 92 (30), 63 (25), 42
(44). Anal. Calcd for C18H20O4 (300.35): C 71.98, H, 6.71%.
Found: C 71.01, H 6.63%.
1 CH), 8.27 (dd, J = 8.0 Hz, J = 1.2 Hz, 1 H, CH). 13C
NMR: 14.3 (Me), 17.9 (Me), 25.7 (CH2), 37.4 (C), 41.4
(CH2), 41.5 (CH2), 109.9 (C), 113.6 (C), 116.4 (CH), 123.0
(CH), 124.3 (CH), 132.5 (CH), 152.7 (C), 156.6 (C), 159.5
(C=O), 165.2 (C=O). EI-MS: 273 (M++1, 95), 272 (M+, 85),
257 (65), 244 (58), 229 (100), 121 (60), 92 (42). Anal. Calcd
for C16H16O4 (272.30): C 70.58, H 5.92%. Found: C 69.22, H
5.59%.
3
4
Preparation of 4-Aryl-3,4-Dihydro-2H,5H-Pyrano[3,2-
c]Chromene-2,5-Diones (10)
4-Isobutyl-4-Methyl-3,4-Dihydro-2H,5H-Pyrano[3,2-c]Chromene-
2,5-Dione (4d)
General Procedure [16]
To a stirred solution of benzaldehyde (0.21 g, 2 mmol) and
Meldrum’s acid (0.29 g, 2 mmol) in 50% aqueous EtOH (10
mL) was added 4-hydroxycoumarin (0.32 g, 2 mmol) and
White powder, yield: 0.37 g (65%), m.p. 107-108°C. IR
1
(KBr) (ꢀmax/cmꢁ1): 1797, 1710, 1620, 1359 cm-1. H NMR:
3
3
0.93 (d, J = 6.6 Hz, 3 H, Me), 0.97 (d, J = 6.6 Hz, 3 H,

816 Combinatorial Chemistry & High Throughput Screening, 2010, Vol. 13, No. 9
Sabbaghan et al.
3
2
proline (11.5 mg, 10 mol%). The reaction mixture was stirred at
reflux for 40 min. After completion of the reaction (monitored
by TLC), the precipitate was collected by filtration and washed
by cold 50% aqueous EtOH (5 mL) to afford 10.
NMR: 3.08 (dd, J = 16.1 Hz, J = 1.6 Hz, 1H, CH), 3.17
3 3
(dd, J = 16.1 Hz, J = 7.4 Hz, 1 H, CH), 3.74 (s, 3 H,
3
2
OCH3), 4.48 (dd, J = 7.4 Hz, J = 1.8 Hz, 1 H, CH), 6.82
(d, 3J = 8.6 Hz, 2 H, 2 CH), 7.16 (d, 3J = 8.6 Hz, 2 H, 2 CH),
3
7.34-7.39 (m, 2 H, 2 CH), 7.59 (t, J = 8.2 Hz, 1 H, 1 CH),
7.90 (dd, 3J = 9.0 Hz, 4J = 1.3 Hz, 1 H, CH). 13C NMR: 35.2
(CH2), 36.2 (CH), 55.3 (OCH3), 106.7 (C), 114.7 (2 CH),
116.6 (C), 116.9 (CH), 127.6 (CH), 127.8 (2 CH), 132.7 (C),
132.8 (CH), 153.2 (C), 157.0 (C), 158.5 (C), 159.3 (C),
160.8 (C=O), 164.4 (C=O). EI-MS: 322 (M+, 9), 294 (14),
279 (12), 111 (16), 95 (15), 85 (22), 71 (55), 57 (100), 43
(92). Anal. Calcd for C19H14O5 (322.31): C 70.80, H 4.38%.
Found: C 71.02, H 4.49%.
4-Phenyl-3,4-Dihydro-2H,5H-Pyrano[3,2-c]Chromene-2,5-
Dione (10a)
White powder, yield: 0.55 g (94%), m.p. 69-171°C. IR
1
(KBr) (ꢀmax/cmꢁ1): 1788, 1707, 1630, 1104 cm-1. H NMR:
3.15 (dd, 2J = 16.2 Hz, 3J = 1.7 Hz, 1 H, CH), 3.21 (dd, 2J =
3
3
3
16.2 Hz, J = 7.6 Hz, 1 H, CH), 4.54 (dd, J = 7.6 Hz, J =
3
1.7 Hz, 1 H, CH), 7.26-7-29 (m, 3 H, 3 CH), 7.31 (d, J =
3
6.8 Hz,1 H, CH), 7.32 (d, J = 6.9 Hz, 1 H, CH), 7.36-7-39
(m, 2 H, 2 CH), 7.62 (t, 3J = 7.3 Hz, 1 H, CH), 7.92 (dd, 3J =
4-(4-Chlorophenyl)-3,4-Dihydro-2H,5H-Pyrano[3,2-c]Chromene-
2,5-Dione (10e)
8.2 Hz, J = 1.6 Hz, 1 H, CH). 13C NMR: 36.3 (CH2), 36.4
4
(CH), 106.8 (C), 113.9 (C), 117.3 (CH), 123.2 (CH), 125.1
(CH), 127.1 (2 CH), 128.5 (CH), 129.7 (2 CH), 133.4 (CH),
139.8 (C), 153.6 (C), 157.7 (C), 161.2 (C=O), 164.7 (C=O).
EI-MS: 292 (M+, 8), 264 (5), 249 (5), 111 (18), 95 (18), 85
(30), 71 (58), 57 (100), 43 (94). Anal. Calcd for C18H12O4
(292.29): C 73.97, H 4.14%. Found: C 73.70, H 4.31.
White powder, yield: 0.51 g (78%), m.p. 197-199°C. IR
(KBr) (ꢀmax/cmꢁ1): 1781, 1711, 1633, 1096 cm-1. H NMR:
1
3.08 (dd, 2J = 14.7 Hz, 3J = 1.5 Hz, 1 H, CH), 3.20 (dd, 2J =
3
3
3
16.2 Hz, J = 7.7 Hz, 1 H, CH), 4.48 (dd, J = 6.6 Hz, J =
1.0 Hz, 1 H, CH), 7.08 (d, 3J = 8.5 Hz, 2 H, 2 CH), 7.25 (d,
3J = 8.5 Hz, 2 H, 2 CH), 7.32-7.40 (m, 2 H, 2 CH), 7.62 (t, 3J
= 7.2 Hz, 1 H, CH), 7.89 (dd, 3J = 8.3 Hz, 4J = 1.3 Hz, 1 H,
CH). 13C NMR: 35.4 (CH2), 35.8 (CH), 105.9 (C), 113.5 (C),
116.7 (CH), 122.9 (CH), 124.4 (CH), 128.1 (2 CH), 128.7
(CH), 129.5 (2 CH), 134.0 (C), 137.9 (C), 153.3 (C), 157.4
(C), 160.6 (C=O), 163.9 (C=O). EI-MS: 326 (M+, 6), 288
(8), 283 (5), 111 (25), 95 (22), 85 (25), 71 (59), 57 (100), 43
(85). Anal. Calcd for C18H11ClO4 (326.73): C 66.17, H
3.39%. Found: C 65.39, H 3.28%.
4-(3-Bromophenyl)-3,4-Dihydro-2H,5H-Pyrano[3,2-c]Chromene
-2,5-Dione (10b)
White powder, yield: 0.68 g (92%), m.p. 170-172°C. IR
1
(KBr) (ꢀmax/cmꢁ1): 1736, 1692, 1449, 1109 cm-1. H NMR:
3.13 (dd, 2J = 16.2 Hz, 3J = 1.6 Hz, 1 H, CH), 3.21 (dd, 2J =
3
2
3
16.2 Hz, J = 7.7 Hz, 1 H, CH), 4.54 (dd, J = 7.7 Hz, J =
1.6 Hz, 1 H, CH), 7.16-7-22 (m, 2 H, 2 CH), 7.38-7.42 (m, 4
3
3
H, 4 CH), 7.64 (t, J = 7.3 Hz, 1 H, CH), 7.92 (dd, J = 8.0
Hz, 4J = 1.3 Hz, 1 H, CH).13C NMR: 36.0 (CH2), 36.3 (CH),
105.9 (C), 113.9 (C), 117.4 (CH), 123.3 (CH), 123.8 (C),
125.2 (CH), 125.6 (CH), 130.3 (CH), 131.3 (CH), 131.7
(CH), 133.6 (CH), 142.0 (C), 153.7 (C), 158.0 (C), 161.0
(C=O), 164.1 (C=O). EI-MS: 371 (M+, 11), 343 (16), 328
(18), 111 (17), 95 (16), 85 (35), 71 (55), 57 (100), 43 (100).
Anal. Calcd for C18H11BrO4 (371.2): C 58.25, H 2.99%.
Found: C 58.42, H 3.05%.
4-(2-Chlorophenyl)-3,4-Dihydro-2H,5H-Pyrano[3,2-c]Chromene-
2,5-Dione (10f)
White powder; yield: 0.49 g (75%), m.p. 212-214°C. IR
(KBr) (ꢀmax/cmꢁ1): 1792, 1701, 1623, 1100 cm-1. H NMR:
1
3.12 (dd, 2J = 14.9 Hz, 3J = 1.8 Hz,1 H, CH), 3.18 (dd, 2J =
3
2
3
14.9 Hz, J = 7.2 Hz, 1 H, CH), 4.59 (dd, J = 7.2 Hz, J =
1.8 Hz, 1 H, CH), 6.95 (d, 3J = 8.5 Hz, 1 H, CH), 7.15 (t, 3J
= 7.2 Hz, 1 H, CH), 7.23 (t, 3J = 7.2 Hz, 1 H, CH), 7.40-7.46
(m, 3 H, 3 CH), 7.66 (t, 3J = 7.9 Hz, 1 H, CH), 7.95 (d, 3J =
7.9 Hz, 1 H, CH).13C NMR: 33.5 (CH2), 35.0 (CH), 104.8
(C), 113.4 (C), 117.1 (CH), 122.9 (CH), 124.7 (CH), 126.9
(CH), 127.6 (CH), 129.5 (CH), 130.7 (C), 133.2 (C), 133.5
(C), 135.9 (C), 153.5 (C), 158.7 (C), 160.3 (C=O), 163.6
(C=O). EI-MS: 326 (M+, 8), 288 (12), 283 (12), 111 (16),95
(19), 85 (28), 71 (60), 57 (100), 43 (92). Anal. Calcd for
C18H11ClO4 (326.73): C 66.17, H 3.39%. Found: C 65.90, H
3.31%.
4-(4-Methylphenyl)-3,4-Dihydro-2H,5H-Pyrano[3,2-c]Chromene-
2,5-Dione (10c)
White powder, yield: 0.52 g (85%), m.p. 68-170 °C. IR
1
(KBr) (ꢀmax/cmꢁ1): 1785, 1701, 1658, 1097 cm-1. H NMR:
3
2.29 (s, 3 H, CH3), 3.11 (dd, 2J = 16.1 Hz, J = 1.8 Hz,1 H,
CH), 3.18 (dd, 2J = 16.1 Hz, 3J = 7.5 Hz, 1 H, CH), 4.48 (dd,
3
3
3J = 7.5 Hz, J = 1.8 Hz, 1 H, CH), 7.08 (d, J = 6.0 Hz, 2
3
H, 2 CH), 7.12 (d, J = 6.0 Hz, 2 H, 2 CH), 7.34-7.40 (m, 2
H, 2 CH), 7.62 (t, 3J = 7.2 Hz, 1 H, 1 CH), 7.90 (dd, 3J = 8.0
Hz, J = 1.4 Hz, 1 H, CH). 13C NMR: 21.0 (CH3), 35.6
4
4-(2-Methylphenyl)-3,4-Dihydro-2H,5H-Pyrano[3,2-c]Chromene-
2,5-Dione (10g)
(CH2), 36.1 (CH), 106.6 (C), 113.7 (C), 116.9 (CH), 122.8
(CH), 126.4 (CH), 126.5 (2 CH), 129.3 (CH), 129.9 (2 CH),
136.4 (C), 137.8 (C), 153.2 (C), 157.1 (C), 160.7 (C=O),
164.3 (C=O). EI-MS: 306 (M+, 7), 278 (12), 263 (10), 111
(15), 95 (15), 85 (25), 71 (55), 57 (100), 43 (96). Anal. Calcd
for C19H14O4 (306.32): C 74.50, H 4.61%. Found: C 74.32, H
4.49%.
White powder, yield: 0.50 g (81%), m.p. 192-195°C. IR
(KBr) (ꢀmax/cmꢁ1): 1780, 1710, 1638, 1102 cm-1. H NMR:
1
2.51 (s, 3 H, CH3), 2.92 (dd, 2J = 15.9 Hz, 3J = 2.1 Hz, 1 H,
CH), 3.18 (dd, 2J = 15.9 Hz, 3J = 7.8 Hz, 1 H, CH), 4.73 (dd,
3J = 7.8 Hz, 3J = 2.1 Hz, 1 H, CH), 6.88 (d, 3J = 7.5 Hz, 1 H,
3
3
CH), 7.07 (t, J = 6.0 Hz, 1 H, CH), 7.15 (t, J = 7.2 Hz, 1
H, 1 CH), 7.22 (t, 3J = 7.3 Hz, 1 H, CH), 7.35-7.38 (m, 2 H,
2 CH), 7.61 (t, 3J = 7.6 Hz, 1 H, 1 CH), 7.92 (d, 3J = 7.6 Hz,
1 H, CH). 13C NMR: 20.3 (CH3), 33.3 (CH2), 36.5 (CH),
107.3 (C), 114.4 (C), 117.8 (CH), 123.6 (CH), 125.5 (CH),
125.6 (CH), 127.7 (CH), 128.8 (CH), 132.3 (CH), 133.8
4-(4-Methoxyphenyl)-3,4-Dihydro-2H,5H-Pyrano[3,2-c]Chromene-
2,5-Dione (10d)
White powder, yield: 0.53 g (83%), m.p. 143-145°C. IR
1
(KBr) (ꢀmax/cmꢁ1): 1777, 1699, 1659, 1660, 1098 cm-1. H

Synthesis of Functionalized Chromenes from Meldrum’s Acid
Combinatorial Chemistry & High Throughput Screening, 2010, Vol. 13, No. 9 817
(CH), 136.4 (C), 138.3 (C), 154.1 (C), 158.7 (C), 161.4
(C=O), 164.8 (C=O). EI-MS: 306 (M+, 6), 278 (12), 263
(12), 111 (15), 95 (15), 85 (22), 71 (55), 57 (98), 43 (100).
Anal. Calcd for C19H14O4 (306.32): C 74.50, H 4.61%.
Found: C 74.21, H 4.57%.
REFERENCES
[1]
(a) Cagniant, P.; Cagniant, D. In Advances in Heterocyclic
Chemistry; Katritzky, A.R., Boulton, A.J., Eds.; Academic Press:
New York, 1975 Vol.18, p 337. (b) Nicolaou, K.C.; Pfefferkorn,
J.A.; Roecker, A.J.; Cao, G.Q.; Barluenga, S.; Mitchell, H.J.
Natural product-like combinatorial libraries based on privileged
structures. 1. General principles and solid-phase synthesis of
benzopyrans. J. Am. Chem. Soc., 2000, 122, 9939-9953.
Green, G.R; Evans, J.M.; Vong., A.K. in Comprehensive
Heterocyclic Chemistry II: Katritzky, A.R.; Rees, C.W.; Scriven,
E.F.; Eds.; Pergamon Press, Oxford, USA, 1995, Vol. 5, p. 469.
Foye, W.O. Principi Di Chemico Frmaceutica, Piccin, Padova,
Italy, 1991.
4-(1-Naphthyl)-3,4-Dihydro-2H,5H-Pyrano[3,2-c]Chromene-2,5
-Dione (10h)
[2]
White powder, yield: 0.64 g (88%), m.p. 246-248 °C. IR
1
(KBr) (ꢀmax/cmꢁ1): 1800, 1711, 1638, 1102 cm-1. H NMR:
[3]
[4]
3.21 (dd, 1 H, 2J = 15.8 Hz, 3J = 7.6 Hz, CH), 3.30 (dd, 1 H,
3
3
2J = 15.8 Hz, J = 1.7 Hz, CH), 5.43 (dd, 1 H, J = 7.6 Hz,
Konkoy, C.S.; Fick, D.B.; Cai, S.X.; Lan, N.C.; Keana, J.F.W.;
PCT Int Appl WO 0075123, 2000, Chem. Abstr., 2001, 134,
29313a.
3J = 1.7 Hz, CH), 7.12 (d, 1 H, J = 7.1 Hz, CH), 7.35 (t, 1
3
H, 3J = 8.0 Hz, CH), 7.46-7.49 (m, 2 H, 2 CH), 7.60 (t, 1 H,
[5]
(a) Pastine, S.J.; Youn, S.W.; Sames, D. Pt V-Catalyzed cyclization
of arene-alkyne substrates via intramolecular electrophilic
hydroarylation. Org. Lett., 2003, 5, 1055-1058; (b) Youn, S.W.;
Pastine, S.J.; Sames, D. Pt(IV)-catalyzed cyclization of arene–
alkyne substrates via C–H bond functionalization. Tetrahedron,
2003, 59, 8859-8868; (c) Hardouin, C.; Burgaud, L.; Valleix, A.;
Doris, E. Enantioselective synthesis of chromenes. Tetrahedron
Lett., 2003, 44, 435-437; (d) Shi, L.; Narula, C.K.; Mak, K.T.; Kao,
L.; Xu, Y.; Heck, R.F. Palladium-catalyzed cyclizations of
bromodialkenyl ethers and amines. J. Org. Chem., 1983, 48, 3894-
3900.
3J = 7.1 Hz, CH), 7.68 (t, 1 H, J = 8.3 Hz, CH), 7.73 (t, 1
3
H, 3J = 7.7 Hz, CH), 7.83 (d, 1 H, 3J = 8.2 Hz, CH), 7.96 (d,
1 H, J = 7.9 Hz, CH), 8.03 (dd, 1 H,3J = 7.9 Hz, J = 1.5
3
4
Hz, CH), 8.16 (d, 1 H, J = 8.5 Hz, CH). 13C NMR: 32.5
3
(CH2), 36.5 (CH), 106.2 (C), 113.9 (C), 117.5 (CH), 122.8
(CH), 123.2 (CH), 123.3 (CH), 125.2 (CH), 125.8 (CH),
126.6 (CH), 127.4 (CH), 129.4 (CH), 129.9 (CH), 130.8 (C),
133.5 (CH), 134.3 (C), 135.0 (C), 153.8 (C), 159.1(C), 161.0
(C=O), 164.1 (C=O). EI-MS: 342 (M+, 7), 314 (14), 309
(12), 271 (12), 95 (13), 85 (22), 71 (54), 57 (100), 43 (95).
Anal. Calcd for C22H14O4 (342.35): C 77.19, H 4.12. Found:
C 77.00, H 4.07.
[6]
Kuwada, T.; Harada, K.; Nobuhiro, J.; Choshi, T. A new synthesis
of 6-substituted pyrido [2,3-d]pyrimidines. Heterocycles, 2002, 57,
2081-2090.
[7]
[8]
Wang, Q.; Finn, M.G. 2H-Chromenes from salicylaldehydes by a
catalytic petasis Reaction. Org. Lett., 2000, 2, 4063-4065.
Broom, A.D.; Shim, J.L.; Anderson, G.L. Pyrido[2,3-
d]pyrimidines. IV. Synthetic studies leading to various
oxopyrido[2,3-d]pyrimidines. J. Org. Chem., 1976, 41, 1095-1099.
Yu, N.; Aramini, J.M.; Germann, M.W.; Huang, Z. Reactions of
salicylaldehydes with alkyl cyanoacetates on the surface of solid
catalysts: syntheses of 4H-chromene derivatives. Tetrahedron Lett.,
2000, 41, 6993-6996.
Ethyl 2,5-Dioxo-3,4-Dihydro-2H,5H-Pyrano[3,2-c]Chromene-4-
Carboxylate (10i)
[9]
White powder, yield: 0.49 g (84%), m.p. 210-214°C. IR
(KBr) (ꢀmax/cmꢁ1): 1646, 1615, 1289, 1268, 1199 cm-1 1H
.
NMR: 1.74 (t, 3J = 7.3 Hz, 3 H, Me), 3.48 (dd, 1 H, 2J = 18.2
3
2
3
[10]
[11]
Sheibani, H.; Mosslemin, M.H.; Behzadi, S.; Islami, M.R.; Saidi,
K. Synthesis, 2006, 3, 435-439.
Hz, J = 8.7 Hz, CH), 3.51 (dd, 1 H, J = 18.2 Hz, J = 8.7
Hz, CH), 3.86 (dd, 1 H, 2J = 9.1 Hz, 3J = 4.6 Hz, CH), 4.68-
4.77 (m, 2 H, CH), 7.78-7.82 (m, 2 H, 2 CH), 7.88 (d, 1 H, 3J
Lacova, M.; Stankovicova, H.; Boha, A.; Kotzianova, B.
Convenient synthesis and unusual reactivity of 2-oxo-2H,5H-
pyrano[3,2-c]chromenes. Tetrahedron, 2008, 64, 9646-9653
Ahluwalia, V.K.; Kumar, R.; Khurana, A.; Bhatla, R. A convenient
synthesis of 1,3-diaryl-1,2,3,4,-tetrahydro-5,7,7-trimethyl-4-oxo-2-
thioxo-7H-pyrano[2,3-d]pyrimidines. Tetrahedron, 1990, 46, 3953-
3956.
= 8.0 Hz, CH), 8.11 (t, 1 H, J = 6.0 Hz, CH). 13C NMR:
3
13.9 (CH3), 35.1 (CH2), 37.8 (CH), 62.3 (CH2), 92.1 (C),
116.4 (C), 116.7 (CH), 124.1 (CH), 124.2 (CH), 132.4 (CH),
153.7 (C), 162.8 (C), 166.9 (C=O), 168.4 (C=O), 173.1
(C=O). EI-MS: 288 (M+, 8), 263 (5), 248 (5), 233 (18), 85
(52), 71 (40), 57 (100), 43 (90). Anal. Calcd for C15H12O6
(288.25): C 62.50, H 4.20, Found: C 62.12, H 4.12.
[12]
[13]
[14]
Abdolmohammadi, S.; Balalaie, S. Novel and efficient catalysts for
the one-pot synthesis of 3,4-dihydropyrano[c]chromene derivatives
in aqueous media. Tetrahedron Lett., 2007, 48, 3299-3303.
Yavari, I.; Hossaini, Z.; Sabbaghan, M. A synthesis of pyrrolo[2,1-
a]isoquinolines through the reaction of activated acetylenes and
isoquinoline in the presence of ethyl bromopyruvate. Tetrahedron
Lett., 2006, 47, 6037-6040.
ACKNOWLEDGEMENT
This work was supported by the Research Council of
Shahid Rajaee Teacher Training University.
[15]
[16]
Yavari, I.; Sabbaghan, M.; Hossaini, Z. Reaction between alkyl
isocyanides and isopropylidene Meldrum’s acid in the presence of
bidentate nucleophiles. Mol. Divers., 2007, 11, 1-5.
Yavari, I.; Sabbaghan, M.; Hossaini, Z. Proline promoted efficient
synthesis of 4-Aryl-3,4-dihydro-2H,5H-pyrano[3,2-c]chromene-
2,5-diones in aqueous media. Synlett., 2008, 15, 1153-1154.
Received: February 16, 2010
Revised: March 20, 2010
Accepted: May 24, 2010