Novel isocyanide-based three-component synthesis of substituted 9Hfuro[ 2,3-f]chromene-8,9-dicarboxylates in water

Article abstract of DOI:10.2174/138620712800194495

Three-component reaction of 1-(6-hydroxy-2-isopropenyl-1-benzofuran-yl)-1- ethanone, dialkyl acetylenedicarboxylates and isocyanides in water was described as efficient and green synthetic procedure for preparation of 9Hfuro[ 2,3-f]chromene-8,9-dicarboxyl

Full text of DOI:10.2174/138620712800194495

Combinatorial Chemistry & High Throughput Screening, 2012, 15, 433-437
433
Novel Isocyanide-Based Three-Component Synthesis of Substituted 9H-
furo[2,3-f]chromene-8,9-Dicarboxylates in Water
Faramarz Rostami-Charati*,1, Zinatossadat Hossaini2 and Mohammad A. Khalilzadeh2
1Department of Chemistry, Faculty of Science, Gonbad Kavous University, P.O. Box 163, Gonbad, Iran
2Department of Chemistry, Qaemshahr Branch, Islamic Azad University, Qaemshahr, Iran
Abstract Three-component reaction of 1-(6-hydroxy-2-isopropenyl-1-benzofuran-yl)-1-ethanone, dialkyl acetylenedi-
carboxylates and isocyanides in water was described as efficient and green synthetic procedure for preparation of 9H-
furo[2,3-f]chromene-8,9-dicarboxylates in excellent yield. In these reactions, 1-(6-hydroxy-2-isopropenyl-1-benzofuran-
yl)-1-ethanone was extracted from rhizomes of Petasites hybridus from northern Iran. The structure of this compound was
1
determined by H, 13C-NMR and IR spectroscopy and confirmed by X-ray diffraction analysis. This procedure provides
rapid access to novel and diversely substituted 9H-furo[2,3-f]chromene-8,9-dicarboxylate derivatives.
O
O
CH3
HO
CO2R
CO2R
CH3
H
CH3
CH3
H
_
H2O
+
N
H
R'
C
O
+
+
O
H
r.t., 8h
O
N
CO2R
R'
H
CO2R
Keywords: 1-(6-hydroxy-2-isopropenyl-1-benzofuran-yl)-1-ethanone, chromene, dialkyl acetylenedicarboxylates, isocyanides,
Petasites hybridus, three-component reactions, X-ray diffraction.
1. INTRODUCTION
the treatment of severe migraine and MS diseases.
Phytochemical analyses of Petasites hybridus extracts reveal
different patterns of medicinal products and a few reports
were observed about the tilted plant [16-19]. Herein, we
describe an efficient synthesis of 9H-furo[2,3-f]chromene-
8,9-dicarboxylates via the reaction of 1-(6-hydroxy-2-
isopropenyl-1-benzofuran-yl)-1-ethanone 1, dialkyl acetyl-
enedicarboxylate 2 and isocyanides 3 in water as the solvent
at room temperature (Scheme 1).
Chromenes represent a chief class of compounds that
were existed in natural compounds and curiosity in their
chemistry carries on unabated because of their convenience
as biologically active representative [1-3]. The key bicyclic
ring system of chromenes has motivated a number of various
synthetic approaches [4, 5]. Many natural and synthetic
chromone derivatives have identical biological and
pharmacological activities, involving antivira [6], antiallergic
[7] and neuroleptic [8] activity. MCRs that contain
isocyanides are considerably the most variable reactions in
terms of scaffolds and multitalented compounds [9-14].
Benzofuran derivatives exist in some natural products. For
example, 1-(6-hydroxy-2-isopropenyl-1-benzofuran-yl)-1-
ethanone 1 was extracted from Rhizomes of Petasites
hybridus from northern Iran [15] (Fig. 1).
2. RESULTS AND DISCUSSION
As indicated in Scheme 1, 1-(6-hydroxy-2-isopropenyl-1-
benzofuran-yl)-1-ethanone 1, with activated acetylenes 2 and
isocyanides 3 undergo a 1:1:1 addition reaction in water (the
activated acetylenes and 1-(6-hydroxy-benzofuran derivative
are combined first and then isocyanides are added) to
produce 9H-furo[2,3-f]chromene-8,9-dicarboxylate derivatives
4 in 83–94 % yields (Scheme 1).
O
H3C
HO
CH3
H
Structures of compounds 4a–4h were deduced from their
1
1
IR, mass, H NMR and 13C NMR spectra. The H NMR
spectrum of 4a exhibited 10 singlets for the tert-butyl (ꢀ 1.38
ppm), methyl (2.12 and 2.58), methoxy (3.75 and 3.82 ppm),
and methine (ꢀ 4.87, 5.22, 5.64, 7.04, and 7.85 ppm) protons
along with one singlet for NH proton at ꢀ 8.74 ppm. The
proton decoupled 13C NMR spectrum of 4a showed 28
distinct resonances in agreement with the proposed structure.
Three single resonances at ꢀ = 164.2, 169.1 and 201.3 ppm
are observed in the 13C NMR spectrum of 4a, which are
attributed to the carbonyl groups.
O
H
Fig. (1). Structure of the extracted 1-(6-hydroxy-2-isopropenyl-1-
benzofuran-yl)-1-ethanone.
The structure of 1 was assigned by 1H and 13NMR and IR
spectra [15]. This compound is very soluble in water. It is
noteworthy to mention that these classes of compounds have
potent biological and medicinal properties and are used in
*Address correspondence to this author at the Department of Chemistry,
Faculty of Science, Gonbad Kavous University, P.O. Box 163, Gonbad,
Iran; Tel.: +981722221802; Fax: +981722224060;
Although, we have not established the mechanism of the
reaction between the isocyanides and the acetylenic esters in
E-mail: f_rostami_ch@yahoo.com
1875-5402/12 $58.00+.00
© 2012 Bentham Science Publishers

434 Combinatorial Chemistry & High Throughput Screening, 2012, Vol. 15, No. 5
Charati et al.
O
O
CO2R
CH3
H
CH3
CH3
_
H2O
CH3
HO
+
N
H
R'
C
O
+
+
O
H
r.t., 8h
O
CO2R
H
N
CO2R
R'
H
CO2R
2
1
3
4
R
R'
2, 3,4
a
Yield (%) of 4
tBu
tBu
Me
90
89
Et
Me
Et
b
c
92
94
cyclohexyl
cyclohexyl
d
e
Me
Et
1,1,3,3-tetramethylbutyl 87
1,1,3,3-tetramethylbutyl 83
f
g
Me
Et
CH2CO2Et
CH2CO2Et
89
85
h
Scheme 1. Three-component condensation reactions of isocyanides, activated acetylenes and 1-(6-hydroxy-2-isopropenyl-1-benzofuran-yl)-
1-ethanone.
the presence of the 1-(6-hydroxy-2-isopropenyl-1-
benzofuran-yl)-1-ethanone 1, a possible explanation is
proposed in Scheme 2. On the basis of the well-established
chemistry of isocyanides [20-25], it is reasonable to assume
that the compound 5 results from an initial addition of the
isocyanide to the acetylenic ester [26-28] add to 1-(6-
hydroxy-2-isopropenyl-1-benzofuran-yl)-1-ethanone 1 resulting
in the formation of 6 and 7. Intermediate 8 undergoes
were carried out with a Perkin-Elmer model 240-C
apparatus. The results of elemental analyses (C, H, N) were
within 0.4% of the calculated values.
GENERAL PROCEDURE
To a stirred solution of 1-(6-hydroxy-2-isopropenyl-1-
dialkyl
benzofuran-yl)-1-ethanone
(2
mmol)
and
acetylenedicarboxylates (2 mmol) in water as the solvent,
isocyanide (2 mmol) was added slowly. The reaction mixture
was stirred for 8 h at room temperature. The resulting
precipitate was separated by filtration and recrystallized from
diethyl ether (Et2O) to afford the pure title compounds.
cyclization to generate 9H-furo[2,3-f]chromene-8,9-
dicarboxylates 4a-h.
3. CONCLUSION
In conclusion, we have developed a convenient and one-
pot method for preparing stabilized 9H-furo[2,3-f]chromene-
8,9-dicarboxylates. The present method carries the advantage
that, not only is the reaction performed under neutral
conditions, but also the substrates can be reacted without any
prior activation or modification. The simplicity of the
present procedure makes it an interesting alternative to
complex multistep approaches. Also one precursor for the
reaction is a natural compound and the reaction was
performed in water as the solvent.
Dimethyl 5-acetyl-7-(tert-butylamino)-2-isopropenyl-9H-
furo[2,3-f]chromene-8,9-dicarboxylate (4a)
White powder, mp 120-122ꢁC, yield: 0.79 g (90%). IR
(KBr) (ꢀmax/cm-1): 1738, 1732, 1723, 1545 and 1242 cm-1. 1H
NMR: ꢀ = 1.38 (9 H, s, Me3C), 2.12 (3 H, s, Me), 2.58 (3 H,
s, Me), 3.74 (3 H, s, MeO), 3.80 (3 H, s, MeO), 4.87 (1 H, s,
CH), 5.22 (1 H, s, CH), 5.64 (1 H, s, CH), 7.04 (1 H, s, CH),
7.85 (1 H, s, CH), 8.74 (1 H, s, NH) ppm. 13C NMR: ꢀ = 18.6
(Me), 27.3 (Me), 29.5 (Me3C), 40.6 (CH), 46.7 (C), 51.4
(MeO), 52.0 (MeO), 73.4 (C), 110.8 (C), 111.4 (CH), 114.2
(CH2), 117.5 (C), 121.0 (C), 122.8 (CH), 137.5 (C), 152.4
(C), 152.9 (C), 159.2 (C), 160.4 (C), 164.2 (C=O), 169.1
(C=O), 201.3 (C=O) ppm. MS: m/z (%) = 441 (M+, 10), 410
(45), 398 (85), 379 (68), 43 (100), 31(86). Anal. Calc. for
C24H27NO7 (441.48): C, 65.30; H, 6.16; N, 3.17 found: C,
65.23; H, 6.10; N, 3.12%.
MATERIAL AND METHODS
1-(6-hydroxy-2-isopropenyl-1-benzofuran-yl)-1-ethanone
was extracted from rhizomes of Petasites hybridus in
northern Iran [15]. Other chemicals were obtained from
Fluka and were used without further purification. Melting
points were measured on a Kofler hot stage apparatus and
are uncorrected. 1H NMR and 13C NMR spectra were
obtained with a Bruker FT-500 spectrometer in chloroform-
d1, and tetramethylsilane (TMS) was used as an internal
standard. Mass spectra were recorded with a Finnigan Mat
TSQ-70 spectrometer. Infrared (IR) spectra were acquired on
a Nicollet Magna 550-FT spectrometer. Elemental analyses
Diethyl 5-acetyl-7-(tert-butylamino)-2-isopropenyl-9H-
furo[2,3-f]chromene-8,9-dicarboxylate (4b)
Yellow powder, mp 128-130ꢁC. yield: 0.83 g (89%). IR
(KBr) (ꢀmax/cm-1): 1737, 1734, 1725, 1572 and 1120 cm-1. 1H

9H-furo[2,3-f]chromene-8,9-Dicarboxylates
Combinatorial Chemistry & High Throughput Screening, 2012, Vol. 15, No. 5 435
O
CO2R
H
CO2R
_
CO2R
CO2R
CH3
H
H3C
1
H
C
N
C
O
+
O
_
2 + 3
N
R'
+
+
R'
5
6
7
O
CH3
H
H3C
4
O
O
C
H
H
CO2R
R'
N
CO2R
8
Scheme 2. Possible mechanism for the formation of products 4.
NMR: ꢀ =1H NMR: ꢀ = 1.26 (9 H, s, Me3C), 1.30 (3 H, t, 3J =
7.4 Hz, Me), 1.34 (3 H, t, 3J = 7.4 Hz, Me), 2.10 (3 H, s, Me),
2.52 (3 H, s, Me), 4.15 (2 H, q, 3J = 7.4 Hz, CH2O), 4.24 (2 H,
q, 3J = 7.4 Hz, CH2O), 4.84 (1 H, s, CH), 5.25 (1 H, s, CH), 5.67
(1 H, s, CH), 7.10 (1 H, s, CH), 7.87 (1 H, s, CH), 8.86 (1 H, s,
NH) ppm. 13C NMR: ꢀ = 13.7 (Me), 14.2 (Me), 18.5 (Me), 27.6
(Me), 30.2 (Me3C), 41.2 (CH), 47.3 (C), 62.3 (CH2O), 63.0
(CH2O), 73.5 (C), 112.2 (C), 113.0 (CH), 114.8 (CH2), 118.2
(C), 122.2 (C), 123.4 (CH), 138.2 (C), 153.2 (C), 153.8 (C),
158.6 (C), 159.8 (C), 163.6 (C=O), 168.7 (C=O), 200.7 (C=O)
ppm. Anal. Calc. for C26H31NO7 (469.53): C, 66.51; H, 6.65; N,
2.98 found: C, 66.46; H, 6.54; N, 2.87%.
m, CH2), 1.63 (2 H, m, CH2), 1.83 (2 H, m, CH2), 2.14 (3 H, s,
Me), 2.65 (3 H, s, Me), 3.79 (1 H, m, N-CH), 4.16 (2 H, q, 3J =
7.5 Hz, CH2O), 4.25 (2 H, q, 3J = 7.5 Hz, CH2O), 4.83 (1 H, s,
CH), 5.35 (1 H, s, CH), 5.76 (1 H, s, CH), 7.22 (1 H, s, CH),
7.87 (1 H, s, CH), 8.92 (1 H, s, NH) ppm. 13C NMR: ꢀ = 13.5
(Me), 14.0 (Me), 18.5 (Me), 24.6 (CH2), 25.0 (CH2), 25.7
(CH2), 27.9 (Me), 32.8 (CH2), 33.5 (CH2), 40.8 (CH), 47.9 (C),
62.5 (CH2O), 63.2 (CH2O), 78.8 (C), 110.3 (C), 112.2 (CH),
112.8 (CH2), 117.6 (C), 121.8 (C), 122.6 (CH), 137.8 (C), 152.7
(C), 153.5 (C), 158.0 (C), 158.6 (C), 162.7 (C=O), 166.3 (C=O),
200.1 (C=O) ppm. Anal. Calc. for C28H33NO7 (495.57): C,
67.86; H, 6.71; N, 2.83 found: C, 67.78; H, 6.64; N, 2.77%.
Dimethyl 5-acetyl-7-(cyclohexylamino)-2-isopropenyl-
9H-furo[2,3-f]chromene-8,9-dicarboxylate (4c)
Dimethyl 5-acetyl-7-(1,1,3,3,-tetramethylbutylamino)-2-
isopropenyl-9H-furo[2,3-f]chromene-8,9-dicarboxylate (4e)
Yellow powder, mp 137-139ꢂC, yield: 0.86 g (92%). IR
(KBr) (ꢀmax/cm-1): 1732, 1730, 1727, 1542 and 1275 cm-1. 1H
NMR: ꢀ = 1.35 (2 H, m, CH2), 1.43 (2 H, m, CH2), 1.48 (2
H, m, CH2), 1.65 (2 H, m, CH2), 1.84 (2 H, m, CH2), 2.10 (3
H, s, Me), 2.62 (3 H, s, Me), 3.76 (3 H, s, MeO), 3.80 (1 H,
m, N-CH), 3.84 (3 H, s, MeO), 4.85 (1 H, s, CH), 5.32 (1 H,
s, CH), 5.72 (1 H, s, CH), 7.16 (1 H, s, CH), 7.85 (1 H, s,
CH), 8.87 (1 H, s, NH) ppm. 13C NMR: ꢀ = 18.8 (Me), 24.5
(CH2), 24.7 (CH2), 25.6 (CH2), 28.3 (Me), 33.4 (CH2), 33.7
(CH2), 41.3 (CH), 48.2 (C), 51.5 (Me), 52.4 (Me), 79.6 (C),
109.7 (C), 112.6 (CH), 113.7 (CH2), 118.5 (C), 122.5 (C),
123.7 (CH), 138.6 (C), 153.4 (C), 153.6 (C), 157.8 (C),
158.4 (C), 163.2 (C=O), 167.8 (C=O), 198.7 (C=O) ppm.
Anal. Calc. for C26H29NO7 (467.52): C, 66.80; H, 6.25; N,
3.00 found: C, 66.85; H, 6.32; N, 3.06%.
Yellow powder, mp 152-154ꢂC, yield: 0.86 g (87%). IR
(KBr) (ꢀmax/cm-1): 1737, 1732, 1730, 1547, 1427 and 1186 cm-1.
1H NMR: ꢀ = 1.03 (9 H, s, CMe3), 1.55 (3 H, s, Me), 1.56 (3 H,
s, Me), 1.83 (2 H, s, CH2), 2.12 (3 H, s, Me), 2.68 (3 H, s, Me),
3.80 (3 H, s, MeO), 3.85 (3 H, s, MeO), 4.78 (1 H, s, CH), 5.28
(1 H, s, CH), 5.76 (1 H, s, CH), 7.23 (1 H, s, CH), 7.93 (1 H, s,
CH), 8.85 (1 H, s, NH) ppm. 13C NMR: ꢀ = 18.9 (Me), 28.4
(Me), 29.7 (C), 31.6 (CMe3), 31.9 (2 Me), 41.2 (CH), 50.4 (C),
52.0 (MeO), 52.6 (MeO), 55.0 (CH2), 80.2 (C), 111.4 (C), 113.5
(CH), 113.8 (CH2), 116.7 (C), 122.0 (C), 122.8 (CH), 138.0 (C),
152.6 (C), 153.8 (C), 158.6 (C), 159.2 (C), 162.9 (C=O), 165.7
(C=O), 200.4 (C=O) ppm. MS: m/z (%) = 497 (M+, 15), 466
(58), 435 (48), 57 (85), 43 (100), 31(78). Anal. Calc. for
C28H35NO7 (497.58): C, 67.59; H, 7.09; N, 2.81 found: C, 67.65;
H, 7.14; N, 2.89%.
Diethyl 5-acetyl-7-(cyclohexylamino)-2-isopropenyl-9H-
furo[2,3-f]chromene-8,9-dicarboxylate (4d)
Diethyl 5-acetyl-7-(1,1,3,3,-tetramethylbutylamino)-2-
isopropenyl-9H-furo[2,3-f]chromene-8,9-dicarboxylate (4f)
pale yellow powder, mp 140-142ꢂC, yield: 0.93 g (94%). IR
(KBr) (ꢀmax/cm-1): 1737, 1730, 1725, 1552, 1415 and 1125 cm-1.
1H NMR: ꢀ = 1.25 (3 H, t, 3J = 7.5 Hz, Me), 1.32 (3 H, t, 3J =
7.4 Hz, Me), 1.37 (2 H, m, CH2), 1.42 (2 H, m, CH2), 1.45 (2 H,
Yellow powder, mp 162-164ꢂC, yield: 0.88 g (83%). IR
(KBr) (ꢀmax/cm-1): 1742, 1735, 1727, 1542, 1387 and 1256
cm-1. 1H NMR: ꢀ = 1.05 (9 H, s, CMe3), 1.28 (3 H, t, 3J = 7.3
3
Hz, Me), 1.32 (3 H, t, J = 7.3 Hz, Me), 1.48 (3 H, s, Me),

436 Combinatorial Chemistry & High Throughput Screening, 2012, Vol. 15, No. 5
Charati et al.
1.52 (3 H, s, Me), 1.78 (2 H, s, CH2), 2.10 (3 H, s, Me), 2.57
(3 H, s, Me), 4.15 (2 H, q, 3J = 7.3 Hz, CH2O), 4.20 (2 H, q,
3J = 7.3 Hz, CH2O), 4.83 (1 H, s, CH), 5.32 (1 H, s, CH),
5.75 (1 H, s, CH), 7.22 (1 H, s, CH), 7.87 (1 H, s, CH), 8.85
(1 H, s, NH) ppm. 13C NMR: ꢀ = 13.6 (Me), 14.3 (Me), 18.7
(Me), 28.5 (Me), 29.6 (C), 31.5 (CMe3), 31.8 (2 Me), 41.4
(CH), 50.2 (C), 62.3 (CH2O), 63.4 (CH2O), 55.2 (CH2), 80.3
(C), 112.4 (C), 113.4 (CH), 114.0 (CH2), 116.8 (C), 121.8
(C), 123.2 (CH), 137.8 (C), 151.8 (C), 152.5 (C), 158.5 (C),
158.7 (C), 162.5 (C=O), 165.3 (C=O), 199.8 (C=O) ppm.
Anal. Calc. for C30H39NO7 (528.64): C, 65.55; H, 7.48; N,
2.66 found: C, 65.47; H, 7.36; N, 2.58%.
REFERENCES
[1]
Miao, H.; Yang, Z. Regiospecific carbonylative annulation of
iodophenol acetates and acetylenes to construct the flavones by a
new catalyst of palladium-thiourea-dppp complex. Org. Lett., 2000,
2, 1765-1768.
[2]
Khalilzadeh, M. A.; Hossaini, Zinatossadat; Baradarani, M.
Hasanni, A. A novel isocyanide-based three-component reaction: a
facile synthesis of substituted 2H-pyran-3,4-dicarboxylates
tetrahedron. Tetrahedron, 2010, 66, 8464-8467.
[3]
[4]
Kumar, P.; Bodas, M. S. A novel synthesis of 4H-Chromen-4-ones
via intramolecular wittig reaction. Org. Lett. 2000, 2, 3821-3823.
Chauder, B. A.; Lopes, C. C.; Lopes, R. S. C.; Dasilva, A. J. M.;
Snieckus, V. Phenylboronic acid mediated synthesis of 2H-
chromenes. Synthesis 1998, 1998 (93), 279-282.
[5]
[6]
Parker, A. K.; Mindt, T. L. Electrocyclic ring closure of the enols
of vinyl quinones. A 2H-chromene synthesis. Org. Lett., 2001, 3,
3875-3878.
De Meyer, N.; Haemers, A.; Mishra, L.; Pandey, H.-K.; Pieters, L.
A. C.; Van den Berghe, D. A.; Vlietinck, A. J. 4'-Hydroxy-3-
methoxyflavones with potent antipicornavirus activity. J. Med.
Chem., 1991, 34, 736-746.
(a) Nohara, A.; Kuriki, H.; Saijo, T.; Ukawa, K.; Murata, T.;
Kanno, M.; Sanno, Y. Antianaphylactic agents. 4. Synthesis and
structure-activity relations of 3-(4-oxo-4H-1-benzopyran-3)acrylic
acids, a new series of antiallergic substances, and some related
compounds. J. Med. Chem., 1975, 18, 34-37; (b) Nohara, A.;
Kuriki, H.; Saijo, T.; Sugihara, H.; Kanno, M.; Sanno, Y. Studies
on antianaphylactic agents. 5. Synthesis of 3-(1H-tetrazol-5-
yl)chromones, a new series of antiallergic substances. J. Med.
Chem., 1977, 20, 141-145; (c) Ellis, G. P.; Becket, G. J. P.; Shaw,
D.; Wilson, N. K.; Vardey, C. J.; Skidmore, I. F. Benzopyrones. 14.
Dimethyl 5-acetyl-7-(2-ethoxy-2-oxoethylamino)-2-iso-
propenyl-9H-furo[2,3-f]chromene-8,9-dicarboxylate (4g)
Pale yellow powder, mp 158-160ꢃC, yield: 0.74g (84%). IR
(KBr) (ꢀmax/cm-1): 1732, 1728, 1725, 1697, 1557 and 1235 cm-1.
1H NMR: ꢀ = 1.31 (3 H, t, 3J = 7.4 Hz, Me), 2.14 (3 H, s, Me),
2.68 (3 H, s, Me), 3.78 (3 H, s, MeO), 3.85 (3 H, s, MeO), 4.20
[7]
3
(2 H, s, CH2), 4.25 (2 H, q, J = 7.3 Hz, CH2O), 4.75 (1 H, s,
CH), 5.32 (1 H, s, CH), 5.84 (1 H, s, CH), 7.25 (1 H, s, CH),
8.03 (1 H, s, CH), 8.95 (1 H, s, NH) ppm. 13C NMR: ꢀ = 14.1
(Me), 19.4 (Me), 27.8 (Me), 41.7 (CH), 50.2 (CH2), 51.7
(MeO), 52.4 (MeO), 60.7 (CH2O), 81.7 (C), 110.4 (C), 112.4
(CH), 113.8 (CH2), 116.7 (C), 119.8 (C), 122.4 (CH), 137.9 (C),
151.2 (C), 153.0 (C), 156.7 (C), 158.6 (C), 164.2 (C=O), 167.4
(C=O), 169.2 (C=O), 200.2 (C=O) ppm. Anal. Calc. for
C24H25NO9 (471.46): C, 61.14; H, 5.34; N, 2.97 found: C, 61.24;
H, 5.42; N, 3.10%.
Synthesis
and
anti-allergic
properties
of
some
N-
tetrazolylcarboxamides and related compounds. J. Med. Chem.,
1978, 21, 1120–1126.
Bolos, J.; Gubert, S.; Anglada, L.; Planas, J. M.; Burgarolas, C.;
Castello, J. M.; Sacrista´n, A.; Ortiz, J. A. 7-[3-(1-
[8]
[9]
Piperidinyl)propoxy]chromenones
antipsychotics. J. Med. Chem., 1996, 39, 2962-2970.
as
potential
atypical
Diethyl 5-acetyl-7-(2-ethoxy-2-oxoethylamino)-2-isopro-
penyl-9H-furo[2,3-f]chromene-8,9-dicarboxylate (4h)
Dömling, A. Recent developments in isocyanide based
multicomponent reactions in applied chemistry. Chem. Rev., 2006,
106, 17-89.
Yellow powder, mp 165-167ꢃC, yield: 0.85g (85%). IR
(KBr) (ꢀmax/cm-1): 1738, 1734, 1728, 1657, 1548 and 1225 cm-1.
1H NMR: ꢀ = 1.25 (3 H, t, 3J = 7.4 Hz, Me), 1.30 (3 H, t, 3J =
7.3 Hz, Me), 1.37 (3 H, t, 3J = 7.4 Hz, Me), 2.10 (3 H, s, Me),
2.63 (3 H, s, Me), 4.12 (2 H, q, 3J = 7.4 Hz, CH2O), 4.22 (2 H, s,
CH2), 4.28 (2 H, q, 3J = 7.4 Hz, CH2O), 4.32 (2 H, q, 3J = 7.3
Hz, CH2O), 4.78 (1 H, s, CH), 5.34 (1 H, s, CH), 5.82 (1 H, s,
CH), 7.23 (1 H, s, CH), 8.12 (1 H, s, CH), 8.86 (1 H, s, NH)
ppm. 13C NMR: ꢀ = 13.7 (Me), 14.0 (Me), 14.3 (Me), 18.7
(Me), 28.2 (Me), 41.5 (CH), 51.4 (CH2), 60.7 (CH2O), 61.3
(CH2O), 62.0 (CH2O), 81.6 (C), 111.4 (C), 112.5 (CH), 114.0
(CH2), 117.0 (C), 120.2 (C), 122.8 (CH), 138.2 (C), 151.7 (C),
152.7 (C), 155.6 (C), 157.8 (C), 164.3 (C=O), 166.4 (C=O),
168.8 (C=O), 200.3 (C=O) ppm. Anal. Calc. for C26H29NO9
(499.51): C, 62.52; H, 5.85; N, 2.80. found: C, 62.58; H, 5.92;
N, 2.87%.
[10]
[11]
Hulme, C.; Gore, V. Multicomponent reactions. Curr. Med. Chem.,
2003, 10, 51.
Zhu, J. Recent developments in the isonitrile-based
multicomponent synthesis of Heterocycles. Eur. J. Org. Chem.,
2003, 7, 1133-1144.
Dömling, A.; Ugi, I. Multicomponent reactions with isocyanides.
Angew. Chem., Int. Ed., 2000, 39, 3168-3210.
Zhu, J.; Bienayme, H. Multicomponent Reactions; Wiley-VCH:
Weinheim, Germany, 2005.
Dömling, A. Recent advances in isocyanide-based multicomponent
chemistry. Curr. Opin. Chem. Biol., 2002, 6, 306-313.
Khaleghi, F.; Bin Dina, L.; Rostami Charati, F.; Yaacob, W. A.;
Khalilzadeh, M. A. Skelton, B.; Makha, M. A new bioactive
compound from the roots of Petasites hybridus. Phytochem. Lett.,
2011, 4 (3), 254-258.
Debrunner, B.; Meier B. Petasites hybridus: A tool for
interdisciplinary research in phytotherapy. Phannaceutica Acta
Heluetiae, 1998, 72, 359-380.
Chizzola, R.; Ozelsberger, B.; Langer T. Variability in chemical
constituents in Petasites hybridus from Austria. Biochem. Sys.
Ecol., 2000, 28, 421-432.
Agosti, R.; Duke, R. K.; Chrubasik, J. E.; Chrubasik S.
Effectiveness of Petasites hybridus preparations in the prophylaxis
of migraine: A systematic review. Phytomedicine, 2006, 13, 743-
746.
[12]
[13]
[14]
[15]
[16]
[17]
[18]
ACKNOWLEDGEMENTS
The authors gratefully acknowledge ꢄnancial and
spiritual support from the National Endowment for the elite
and Research Council of Gonbad Kavous University.
[19]
[20]
Thomet, O. A. R.; Schapowal, A.; Heinisch, I. V. W. M.;
Wiesmann, U. N.; Simon, H. Anti-inflammatory activity of an
extract of Petasites hybridus in allergic rhinitis. Int.
Immunopharmacol., 2002, 2, 997-1006.
CONFLICT OF INTEREST
Ugi, I. Isonitrile Chemistry; Academic: London, 1971.
Declared none.

9H-furo[2,3-f]chromene-8,9-Dicarboxylates
Combinatorial Chemistry & High Throughput Screening, 2012, Vol. 15, No. 5 437
[21]
Ugi, I. From Isocyanides via four-component condensations to
antibiotic syntheses. Angew. Chem., Int. Ed. Engl., 1982, 21, 810-
819.
Do¨mling, A.; Ugi, I. Multicomponent reactions with isocyanides.
Angew. Chem., Int. Ed., 2000, 39, 3168-3210.
Nair, V.; Viond, A. U.; Nair, J. S.; Sreekanth, A. R.; Rath, N. P.
The reaction of cyclohexyl isocyanide and dimethyl
acetylenedicarboxylate with o- and p-quinones: a novel synthesis of
iminolactones. Tetrahedron Lett., 2000, 41, 6675-6679.
Walborsky, H. M.; Presiasamy, M. P. The Chemistry of Functional
Groups. Wiley: New York, NY, 1983, 20, 835.
[26]
Shaabani, A.; Soleimani, E.; Khavasi, H. R.; Hoffmann, R.;
Rodewald, Ute Ch.; Po¨ttgen, R. An isocyanide-based three-
component reaction: synthesis of fully substituted N-alkyl-2-
triphenylphosphoranylidene glutarimides. Tetrahedron Lett., 2006,
47, 5493-5496.
Shaabani, A.; Soleimani, E.; Sarvary, A.; Rezayan, A. H. A simple
and efficient approach to the synthesis of 4H-furo[3,4-b]pyrans via
a three-component reaction of isocyanides. Bioorg. Med. Chem.
Lett., 2008, 18, 3968-3970.
Alizadeh, A.; Rostamnia S.; Zhu, L-G. Reaction between tert-butyl
isocyanide, dialkyl acetylenedicarboxylates, and aromatic
carboxylic acids: an efficient method for the synthesis of dialkyl
(E)-2-{[benzoyl(tert-butyl)amino]carbonyl}-2-butenedioate
derivatives. Tetrahedron, 2006, 62, 5641-5644.
[22]
[23]
[27]
[28]
[24]
[25]
Marcaccini, S.; Torroba, T. The use of isocyanides in heterocyclic
synthesis. A review. Org. Prep. Proced. Int., 1993, 25, 141-208.
Received: July 20, 2011
Revised: November 10, 2011
Accepted: November 14, 2011