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Scheme 3.
To validate the proposed mechanism, we carried out the syn-
thesis of 4b in two steps (Scheme 3).16 The reaction between 2
and intermediate 5b, which was obtained via the condensation of
4-nitrobenzaldehyde and malononitrile, can give product 4b in
the yield (75%) slightly than the one-pot version (82%). This fact
provided the evidence in support of the proposed pathway.
In conclusion, a series of 4-aryl-cyclopenta[b]pyran derivatives
were designed based on natural product and synthesized effi-
ciently via multi-component reaction under solvent-free condi-
tions. The high yields, short reaction time, eco-friendliness and
the simple workup procedure, make the protocol attractive to syn-
thesize a variety of the fused pyran derivatives. Additionally, the
newly synthesized 4-aryl-cyclopenta[b]pyran derivatives may pro-
vide new class of potential biologically active compound library for
biomedical screening.
Acknowledgments
We are grateful for financial support by Natural Science Foun-
dation of China (No. 20672090 and 200810102050), the Major
Basic Research Project of the Natural Science Foundation of the
Jiangsu Higher Education Institutions (09KJA430003), Natural Sci-
ence Foundation of Xuzhou City(XM09B016), Graduate Foundation
of Xuzhou Normal University (2010YLB029) and Qing Lan Project
(08QLT001).
Supplementary data
14. A triturated mixture of aryl aldehyde 1 (1.0 mmol), malononitrile or ethyl
cyanoacetate 3 (1.0 mmol) was put into an agate mortar for 30 min at 85 °C.
Supplementary data associated with this article can be found, in
Then, added into cyclopentane-1,3-dione
2 (1.0 mmol), the mixture was
maintained in 85 °C. Upon completion, monitored by TLC, the reactant was
cooled to room temperature and was purified by column chromatography
(silica gel, mixtures of ethyl acetate/petroleum ether, 1:1, v/v) to afford the
desired pure product 4. Compound 4b: mp: 201–203 °C; IR (potassium
References and notes
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bromide) (m
, cmÀ1): 3397, 3326, 3214, 2195, 1670, 1519, 1375, 1347, 1233,
1111, 1008, 865, 669; 1H NMR (DMSO-d6): d 8.18 (d, J = 8.4 Hz, 2H, ArH), 7.52
(d, J = 8.8 Hz, 2H, ArH), 7.37 (s, 2H, NH2), 4.44 (s, 1H, ArCH), 2.71–2.83 (m, 2H,
CH2), 2.33–2.45 (m, 2H, CH2). HRMS (ESI) m/z: calcd for: [M+Na]+
C15H11N3O4Na: 320.0647; found: 320.0654.
15. The single-crystal growth was carried out in ethanol at room temperature. X-
ray crystallographic analysis was performed using
diffractometer. Crystal data for 4s: 15H10Cl2N2O2, colorless, crystal
dimension Monoclinic, space group C2/c,
0.20 Â 0.18 Â 0.12 mm,
a = 20.361(6), b = 8.793(3), c = 17.998(6) Å, b = 98.798(6)°, V = 3184(17) Å3,
Mr = 369.21, Z = 8, Dc = 1.540 g/cm3, k = 0.71073 Å, ) = 0.430 mmÀ1
(Mok
a Rigaku Saturn
C
l
a
,
F(0 0 0) = 1528, S = 1.007, R1 = 0.0703, wR2 = 0.1577. CCDC 774770 contains
the supplementary crystallographic data for this Letter. These data can be
obtained free of charge from The Cambridge Crystallographic Data Centre via
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