Microwave-assisted three-component condensation on montmorillonite K10: Solvent-free synthesis of furopyrimidines, furocoumarins, and furopyranones

Article abstract of DOI:10.1081/SCC-200049779

Rapid and efficient one-pot three-component condensation synthesis of furopyrimidines, furocoumarins, and furopyranones are described which occur in the presence of montmorillonite K10 using microwave irradiation under solvent-free conditions.

Full text of DOI:10.1081/SCC-200049779

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Microwave‐Assisted Three‐Component
Condensation on Montmorillonite K10:
Solvent‐Free Synthesis of Furopyrimidines,
Furocoumarins, and Furopyranones
Ahmad Shaabani a , Mohammad Bagher Teimouri a , Sima Samadi a & Kamal
Soleimani a
a Chemistry Department, Shahid Beheshti University, Tehran, Iran
Published online: 12 Apr 2011.
To cite this article: Ahmad Shaabani , Mohammad Bagher Teimouri , Sima Samadi & Kamal Soleimani (2005):
Microwave‐Assisted Three‐Component Condensation on Montmorillonite K10: Solvent‐Free Synthesis of
Furopyrimidines, Furocoumarins, and Furopyranones, Synthetic Communications: An International Journal for
Rapid Communication of Synthetic Organic Chemistry, 35:4, 535-541
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Synthetic Communicationsw, 35: 535–541, 2005
Copyright # Taylor & Francis, Inc.
ISSN 0039-7911 print/1532-2432 online
DOI: 10.1081/SCC-200049779
Microwave-Assisted Three-Component
Condensation on Montmorillonite K10:
Solvent-Free Synthesis of Furopyrimidines,
Furocoumarins, and Furopyranones
Ahmad Shaabani, Mohammad Bagher Teimouri,
Sima Samadi, and Kamal Soleimani
Chemistry Department, Shahid Beheshti University, Tehran, Iran
Abstract: Rapid and efficient one-pot three-component condensation synthesis of
furopyrimidines, furocoumarins, and furopyranones are described which occur in the
presence of montmorillonite K10 using microwave irradiation under solvent-free
conditions.
Keywords: Solvent-free, montmorillonite K10, furopyrimidines, furocoumarins,
furopyranones, microwave
Furopyrimidines and furocoumarins are an important class of compounds,
which exhibit a wide range of biological activities. For example, furo[2,3-d]
pyrimidine derivatives[1] act as sedatives, antihistamines, diuretic, muscle
relaxants, and antiulcer agent, and furocoumarins act presumably related to
the natural defense of plants against fungal attack.[1–4]
The synthesis of furopyrimidines and furocoumarins has received little
attention and only few procedures have been reported in the literature, most
of which relied on multistep reactions with yields being low.[4–10]
Recently, Nair and his coworkers have devised a one-pot synthesis of
furocoumarins and furopyranones.[11] Product yields are relatively good, but
Received in the UK 16 June 2004
Address correspondence to Ahmad Shaabani, Chemistry Department, Shahid
Beheshti University, P.O. Box 19839-4716, Tehran, Iran. Fax: þ98-21-2403041.
E-mail: a-shaabani@cc.sbu.ac.ir

536
A. Shaabani et al.
the reaction times necessary for these yields are very long. For example 14–
16 h under reflux conditions in benzene as a toxic solvent, when furopyranones
are the product and 16–24 h in the case of furocoumarins. Consequently, there
is need to develop a simple, rapid, eco-friendly and easy experimental and
products isolation procedure for the synthesis of these compounds.
In this article we have investigated the potential of microwaves
irradiation to accelerate the reaction of N,N0-dimethylbarbituric acid 1 or
4-hydroxy coumarin or 4-hydroxy-6-methyl-2-pyrone 2, with para-
substituted benzaldehydes 3 and alkyl or aryl isocyanides 4 in the presence
of montmorillonite K10 as an inexpensive inorganic solid support under
solvent-free conditions.
Microwave-enhanced chemical reactions,[12–15] especially on inorganic
solid supports[16,17] and that are conducted under solvent-free conditions,
have attracted attention recently. They offer several advantages over the
conventional reactions in view of the rapid reaction rates, higher yields, and
the avoidance of large volumes of solvent.
Our solvent-free one-pot method simply involves microwave irradiation
of a mixture of para-substituted benzaldehyde 3 and corresponding N,N0-
dimethylbarbituric acid 1 or 4-hydroxy coumarin or 4-hydroxy-6-methyl-2-
pyrone 2 with isocyanide 4 in the presence of montmorillonite K10 to
afford the corresponding products 5 or 6. The reaction is completed in all
cases within 4–5 mins. (see Scheme 1).
1H and 13C NMR spectra of crude product clearly indicated the formation
furopyrimidines 5 or furocoumarines or furopyranones 6. Any product other
than 5 or 6 could not be detected by NMR spectroscopy. The structure of
new compounds 5a, 5b, 6b, 6f, and 6g were deduced from their elemental
1
analysis and their IR, H NMR and 13C NMR spectra. The mass spectra of
these compounds displayed molecular ion peaks or Mþ1 peaks at the
appropriate m/z values (see the Experimental section).
In order to select the best solid support, we carried out the reaction of
4-nitro benzaldehyde, N,N0-dimethylbarbituric acid, and cyclohexyl isocya-
nide on the surface of various supports such as montmorillonite K10, silica
gel, alumina, amberlist resin, and zeolite under microwave irradiation.
Under all conditions, product 5c was produced with good yields (85, 60, 82,
73, and 78%, respectively). The higher yield was obtained with montmorillo-
nite K10 as a solid support.
Yields of products under microwave irradiation under solvent-free con-
ditions in the absence of solid supports and classical heating conditions
were low and the reactants and products adhered to the reaction vessel and
led to irreproducible results.
We have shown the combination of solvent-free supported reagents and
microwave irradiation is a rapid and efficient method for the one-pot three-
component condensation synthesis of furopyrimidines, furocoumarins, and
furopyranones. In this approach the use of large volume of benzene[11] or

Furopyrimidines, Furocoumarins, and Furopyranones
537
Scheme 1.
toluene[7] is avoided, work-up considerably simplified, and safety is increased
by reducing the risk of overpressure and explosions.
EXPERIMENTAL
Melting points were measured on an Electrothermal 9100 apparatus and
are uncorrected. Elemental analyses were performed using a Heraeus

538
A. Shaabani et al.
CHN-O-Rapid analyzer. Mass spectra were recorded on a FINNIGAN-MAT
8430 mass spectrometer operating at an ionization potential of 70 eV. IR
spectra were recorded on a Shimadzu IR-470 spectrometer. 1H and 13C
NMR spectra were recorded on a BRUKER DRX-500 AVANCE spec-
trometer at 500.13 and 125.77 MHz, respectively. NMR spectra were
obtained on solutions in CDCl3 using TMS as internal standard. The
chemicals used in this work were purchased from Merck and Fluka (Buchs,
Switzerland) chemical companies. The microwave oven was a domestic
(maximum 900 W) National model NN-6653 with five select power levels
(one of which were used for this experiment; medium high 70% wattage).
Typical Procedure for Preparation of 5-p-Methoxyphenyl-6-
cyclohexylamino-1,3-dimethylfuro[2,3-d]pyrimidine-2,4(1H,3H)-
dione (5a)
In a 25 mL beaker, cyclohexyl isocyanide (0.121 g, 1.1 mmol), 4-methoxy
benzaldehyde (0.150 g, 1.1 mmol), and N,N0-dimethylbarbituric acid
(0.156 g, 1.0 mmol) were roughly mixed with montmorillonite K10 (0.5 g)
and after 3 min of mechanical stirring, the mixture was irradiated at
medium power for 4 min. Upon completion of the reaction, monitored on
TLC (n-hexane:ethyl acetate, 3:1), the product was extracted in diethyl
ether (2 ꢀ 15 mL), solvent removal of the solid residue was crystallized
from (C2H5)2O-EtOH (1:2) to yield 5a as a cream powder (0.284 g, 74%).
mp 122–1248C. IR (KBr) (nmax, cm21): 3250 (N-H), 1697 and 1630
1
(C55O). H NMR (CDCl3, Me4Si): dH 1.13–1.94 (10 H, m, 5 CH2), 3.11–
3.14 (1 H, m, N-CH), 3.37 and 3.55 (6 H, 2 s, 2 NCH3), 3.43 (1 H, d,
3JHH ¼ 6.5 Hz, NH), 3.83 (3 H, s, OCH3), 6.95 and 7.49 (4 H, 2 d,
3JHH ¼ 8.7 Hz, arom.). 13C NMR (CDCl3, Me4Si): dC 24.81, 25.62 and
33.92 (5 CH2), 28.24 and 29.44 (2 NCH3), 55.30 (N-CH), 55.85 (OCH3),
96.20 (C4a), 105.63 (C5), 113.80 (Cmeta-OCH3), 122.75 (Cpara-OCH3),
130.51 (Cortho-OCH3), 142.44 (C-OCH3), 149.94 (C6), 150.10 (C7a), 150.57
(C2), 158.83 (C4). MS (m/z, %) 383 (Mþ, 83), 300 (100), 273 (51), 243
(27), 172 (30), 108 (10), 67 (75), 41 (73). Anal. Calcd. for C21H25N3O4
(383.44): C, 65.78; H, 6.57; N, 10.96%. Found: C, 65.72; H, 6.32; N, 11.06%.
5-Phenyl-6-cyclohexylamino-1,3-dimethylfuro[2,3-d]pyrimidine-
2,4(1H,3H)-dione (5b)
Light pink crystals (0.273 g, 77%). mp 124–1268C. IR (KBr) (nmax, cm21):
3260 (N-H), 1702 and 1660 (C55O). H NMR (CDCl3, Me4Si): dH 1.09–
1
1.96 (10 H, m, 5 CH2), 3.14–3.20 (1 H, m, N-CH), 3.38 and 3.56 (6 H, 2 s,
3
2 NCH3), 3.57 (1 H, d, JHH ¼ 6.6 Hz, NH), 7.26–7.57 (5 H, m, arom.).

Furopyrimidines, Furocoumarins, and Furopyranones
539
13C NMR (CDCl3, Me4Si): dC 24.81, 25.61 and 34.00 (5 CH2), 28.33 and
29.45 (2 NCH3), 55.60 (N-CH), 96.12 (C4a), 104.61 (C5), 127.00 (Cpara),
128.33 (Cmeta), 129.25 (Cortho), 130.50 (Cipso), 148.93 (C6), 150.50 (C7a),
150.84 (C2), 158.22 (C4). MS (m/z, %) 353 (Mþ, 100), 271 (38), 243 (30),
214 (28), 186 (10), 142 (20), 83 (5), 67 (32). Anal. Calcd. for C20H23N3O3
(353.42): C, 67.97; H, 6.56; N, 11.89%. Found: C, 68.10; H, 6.41; N, 11.75%.
2-(Cyclohexylamino)-3-phenyl-4H-furo[3,2c]chromen-4-one (6b)
Yellow crystals (0.259 g, 72%). mp 130–1318C. IR (KBr) (nmax, cm21): 3420
(N-H), 1721 (C55O), 1584 (C55C). 1H NMR (CDCl3, Me4Si): dH 1.19–2.07
3
(10 H, m, 5 CH2), 3.57 (1 H, m, N-CH), 4.28 (1 H, d, JHH ¼ 8.2 Hz, NH),
7.25–7.78 (8 H, m, arom.). 13C NMR (CDCl3, Me4Si): dC 24.90, 25.53 and
34.13 (5 CH2), 53.68 (N-CH), 97.49, 110.93, 112.86, 116.89, 119.47,
124.15, 126.78, 128.75, 128.64, 129.18, 130.72, 149.80, 151.32, 154.88
(arom. and 2 C55C), 157.92 (C55O). MS (m/z, %) 359 (Mþ, 31), 277 (40),
248 (19), 220 (10), 129 (18), 83 (25), 55 (100). Anal. Calcd. for C23H21NO3
(359.41): C, 76.86; H, 5.89; N, 3.90%. Found: C, 76.73; H, 5.95; N, 3.82%.
2-(Cyclohexylamino)-6-methyl-3-(4-methoxyphenyl)-4H-
furo[3,2c]pyran-4-one (6f)
Yellow crystals (0.258 g, 73%). mp 91–938C. IR (K Br) (nmax, cm21): 3400
(N-H), 1714 (C55O), 1600 (C55C). H NMR (CDCl3, Me4Si): dH 1.15–
1
1.99 (10 H, m, 5 CH2), 2.31 (3 H, s, CH3), 3.37–3.41 (1 H, m, N-CH), 3.82
(1 H, br s, NH), 3.83 (3 H, s, OCH3) 6.31 (1 H, s, C55CH), 6.96 and 7.41
3
(4 H, 2 d, JHH ¼ 8.5 Hz, arom.). 13C NMR (CDCl3, Me4Si): dC 20.05
(CH3), 24.89, 25.56 and 34.17 (5 CH2), 53.86 (N-CH), 55.28 (OCH3),
95.31, 97.02, 108.59, 114.13, 123.15, 130.23, 153.08, 155.10, 156.67,
158.34 (3 C55C and arom.), 159.94 (C55O). MS (m/z, %) 353 (Mþ, 82),
271 (52), 226 (15), 186 (10), 159 (8), 77 (20), 55 (100). Anal. Calcd. for
C21H23NO4 (353.41): C, 71.37; H, 6.56; N, 3.96%. Found: C, 71.50; H,
6.49; N, 4.05%.
2-(Cyclohexylamino)-6-methyl-3-phenyl-4H-furo[3,2c]
pyran-4-one (6g)
Light brown crystals (0.278 g, 70%). mp 126–1288C. 3400 (N-H), 1724
(C55O) 1606 (C55C). H NMR (CDCl3, Me4Si): dH 1.18–2.08 (10 H, m, 5
1
CH2), 2.36 (3 H, s, CH3), 3.47 (1 H, m, N-CH), 4.16 (1 H, br s, NH), 6.37
(1 H, s, C55CH), 7.28–7.55 (5 H, m, C6H5). 13C NMR (CDCl3, Me4Si): dC

540
A. Shaabani et al.
20.45 (CH3), 25.31, 25.95 and 34.57 (5 CH2), 54.08 (N-CH), 95.68, 96.96,
108.89, 126.87, 128.98, 129.36, 131.45, 153.87, 155.54 and 157.13 (3 C55C
and C6H5), 160.08 (C55O). MS (m/z, %) 323 (Mþ, 98), 241 (98), 213 (40),
170 (48), 129 (27), 83 (17), 55 (97), 41 (97). Anal. Calcd. for C20H21NO3
(323.38): C, 74.28; H, 6.55; N, 4.33%. Found: C, 74.30; H, 6.62; N, 4.21%.
ACKNOWLEDGMENT
We gratefully acknowledge financial support from the Research Council of
Shahid Beheshti University.
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