Effective Synthesis of 7-Amino-6-cyano-5-aryl-5H-pyrano[2,3-d]pyrimidine-2,4(1H,3H)-diones under Microwave Irradiation

Article abstract of DOI:10.1081/SCC-120030318

A series of 7-amino-6-cyano-5-aryl-5H-pyrano[2,3-d]pyrimidine-2,4(1H,3H)-diones were synthesized by the reaction of arylidenemalononitrile with barbituric acid under microwave irradiation without catalyst with shorter reaction time and higher yields.

Full text of DOI:10.1081/SCC-120030318

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Effective Synthesis of
7‐Amino‐6‐cyano‐5‐aryl‐5H‐pyrano[2,3‐d]pyrimidine‐2,4(
Under Microwave Irradiation
Yuan Gao a , Shujang Tu b , Tuanjie Li b , Xiaojing Zhang b , Songlei Zhu b , Fang Fang b
Daqing Shi b
a Department of Chemistry, Shenzhen University, Shenzhen, Guangdong, P.R. China
&
b Department of Chemistry, Key Laboratory of Biotechnology on Medical Plant, Xuzhou
Normal University, Jiangsu, Xuzhou, Jiangsu, 221009, P.R. China
Version of record first published: 21 Aug 2006.
To cite this article: Yuan Gao , Shujang Tu , Tuanjie Li , Xiaojing Zhang , Songlei Zhu , Fang Fang & Daqing Shi (2004):
Effective Synthesis of 7‐Amino‐6‐cyano‐5‐aryl‐5H‐pyrano[2,3‐d]pyrimidine‐2,4(1H,3H)‐diones Under Microwave Irradiation,
Synthetic Communications: An International Journal for Rapid Communication of Synthetic Organic Chemistry, 34:7,
1295-1299
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SYNTHETIC COMMUNICATIONSw
Vol. 34, No. 7, pp. 1295–1299, 2004
Effective Synthesis of 7-Amino-6-cyano-5-
aryl-5H-pyrano[2,3-d]pyrimidine-
2,4(1H,3H)-diones Under
Microwave Irradiation
2
2
Yuan Gao,1 Shujang Tu,2, Tuanjie Li, Xiaojing Zhang,
*
Songlei Zhu,2 Fang Fang,2 and Daqing Shi2
1Department of Chemistry, Shenzhen University, Shenzhen,
Guangdong, P.R. China
2Department of Chemistry, Key Laboratory of Biotechnology on Medical
Plant, Xuzhou Normal University, Xuzhou, Jiangsu, P.R. China
ABSTRACT
A
series of 7-amino-6-cyano-5-aryl-5H-pyrano[2,3-d]pyrimidine-
2,4(1H,3H)-diones were synthesized by the reaction of arylidenemalono-
nitrile with barbituric acid under microwave irradiation without catalyst
with shorter reaction time and higher yields.
Key Words: Microwave irradiation; Barbituric acid; Dione; Heterocyclic
compounds.
*
Correspondence: Shujang Tu, Department of Chemistry, Key Laboratory of Biotech-
nology on Medical Plant, Xuzhou Normal University, Jiangsu, Xuzhou, Jiangsu
221009, P.R. China; E-mail: laotu2001@263.net.
1295
DOI: 10.1081/SCC-120030318
0039-7911 (Print); 1532-2432 (Online)
www.dekker.com
Copyright # 2004 by Marcel Dekker, Inc.

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Gao et al.
INTRODUCTION
Recently, much attention has been paid to the development of new
methods for the synthesis of heterocyclic compounds, due to their poten-
tial importance in the fields of pharmaceutical and agricultural drugs.
Pyrimidine derivatives are generally used as antitumors,[1] analgetic
substances,[2] bactericidals,[3] and fungicidal.[4] Sharanin[5] and
Ibrahim[6] reported that 7-amino-6-cyano-5-aryl-5H-pyrano[2,3-d]pyrimi-
dine-2,4(1H,3H)-diones were synthesized by the reaction of arylidene-
malononitrile with barbituric acid under traditional hot reaction condition.
Microwave irradiation is a very useful technique in organic synthesis.[7–9]
In our laboratory, we have reported the synthesis of heterocyclic compounds
under microwave irradiation.[10–14] Here, we would like to further report
a fast, efficient, and simple method for synthesis of 7-amino-6-cyano-
5-aryl-5H-pyrano[2,3-d]pyrimidine-2,4(1H,3H)-diones under microwave
irradiation.
When arylidenemalononitrile (1) and barbituric acid (2) in water under
microwave irradiation without catalyst for 3–5 min (Sch. 1), the desired
products (3) were obtained in good yields.
This reaction may have taken place by an (addition, cyclization) mecha-
nism (Sch. 2). Thus, the Michael addition between arylidenemalononitrile and
barbituric acid gave the intermediate 4, which isomerized to 5. Intramolecular
cyclizative condensation of 5 gave 6, 6 isomerized to 3.
EXPERIMENTAL
Melting points were determined in open capillaries and are uncorrected.
1
IR spectra were recorded on a FT IR-8101 spectrometer. H NMR spectra
were measured on a Bruker DPX 300 MHz spectrometer using TMS as
internal standard, DMSO-d6 as solvent.
Scheme 1.

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7-Amino-6-cyano-5-aryl-5H-pyrano[2,3-d]pyrimidine-2,4(1H,3H)-diones
1297
Scheme 2.
General Procedure for Synthesis of 7-Amino-6-cyano-5-aryl-
5H-pyrano[2,3-d]pyrimidine-2,4(1H,3H)-diones (3)
A dry flask (25 mL) was charged with the arylidenemalononitrile (1)
(5 mmol), barbituric acid (2) (5 mmol), and water (3 mL). The flask was then
connected with refluxing equipment. After microwave irradiation (285 W)
for 3–5 min (as indicated by TLC), the reaction mixture was cooled to
room temperature. The crude products were purified by recrystallization
from 95% ethanol to afford (3).
1
3a: H NMR (DMSO-d6) d: 4.41 (s, 1H, CH), 7.03 (s, 2H, NH2), 7.16
(d, 2H, J ¼ 7.0 Hz, ArH), 7.25 (d, 2H, J ¼ 7.0 Hz, ArH), 10.96 (s, 1H, NH),
11.97 (s, 1H, NH); IR (KBr), n: 3385, 3300, 3251, 3178, 2195, 1720, 1674,
1636 cm21
.
Table 1. Yields of the products.
Reaction
time (min)
Isolated
yield (%)
Entry
Ar
M.p. (8C) (Lit.)
3a
3b
3c
3d
3e
3f
4-Br-C6H4
2-ClC6H4
4-ClC6H4
4-CH3OC6H4
4-FC6H4
3
4
3
4
5
3
5
227–229 (226–227)[5]
213–215 (214–215)[5]
241–242 (240–241)[5]
280–281
225–227 (225–226)[5]
238–239 (237–238)[5]
208–210 (210–211)[5]
94
89
92
90
91
86
92
4-NO2C6H4
C6H5
3g

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Gao et al.
3b: 1H NMR (DMSO-d6) d: 4.74 (s, 1H, CH), 7.00 (s, 2H, NH2), 7.20–7.35
(m, 4H, ArH), 10.93 (s, 1H, NH), 11.97 (s, 1H, NH); IR (KBr), n: 3500, 3308,
3174, 2197, 1711, 1661, 1618cm21
.
1
3c: H NMR (DMSO-d6) d: 4.25 (s, 1H, CH), 7.03 (s, 2H, NH2), 7.22
(d, 2H, J ¼ 6.3 Hz, ArH), 7.31 (d, 2H, J ¼ 6.3 Hz, ArH), 10.96 (s, 1H, NH),
11.97 (s, 1H, NH); IR (KBr), n: 3380, 3301, 3251, 3179, 2197, 1722, 1672,
1633 cm21
.
1
3d: H NMR (DMSO-d6) d: 3.88 (s, 3H, OCH3), 4.16 (s, 1H, CH), 6.94
(s, 2H, NH2), 7.04 (d, 2H, J ¼ 7.0 Hz, ArH), 7.11 (d, 2H, J ¼ 7.0 Hz, ArH)
11.08 (s, 1H, NH), 11.21 (s, 1H, NH); IR (KBr), n: 3421, 3250, 3100, 2198,
1730, 1675, 1600 cm21
.
3e: 1H NMR (DMSO-d6) d: 4.17 (s, 1H, CH), 7.04 (s, 2H, NH2), 7.09–7.44
(m, 4H, ArH), 10.93 (s, 1H, NH), 11.92 (s, 1H, NH); IR (KBr), n: 3380, 3291,
3249, 3180, 2197, 1716, 1674, 1635cm21
.
3f: 1H NMR (DMSO-d6) d: 4.42 (s, 1H, CH), 7.16 (s, 2H, NH2), 7.47–8.14
(m, 4H, ArH), 11.01 (s, 1H, NH), 12.07 (s, 1H, NH); IR (KBr), n: 3380, 3291,
3181, 2198, 1711, 1675, 1628cm21
.
3g: 1H NMR (DMSO-d6) d: 4.22 (s, 1H, CH), 6.91 (s, 2H, NH2), 7.16–7.28
(m, 5H, ArH), 10.91 (s, 1H, NH), 11.91 (s, 1H, NH); IR (KBr), n: 3400, 3301,
3261, 3165, 2195, 1711, 1675, 1630cm21
.
ACKNOWLEDGMENTS
We thank the Nature Science Foundation of the Jiangsu Province
(No. BK2001142) and the Nature Science Foundation of Jiangsu Education
Department (No. 01KJB150008) and the Key Laboratory of Chemical
Engineering and Technology of the Jiangsu Province Open Foundation (No.
KJS02060) and the Nature Science Foundation of the Guangdong Province
(No. 31792) for financial support.
REFERENCES
1. Suguira, K.; Schmid, A.F.; Schmid, M.M.; Brown, F.G. Cancer
Chemother. Rep. Part 2 1973, 3 (1), 231.
2. Regnier, G.L.; Canevar, R.J.; Le Douarec, J.C.; Halstop, S.; Daussy, J.
J. Med. Chem. 1972, 15, 295.
3. Pershin, N.G.; Sherbakova, L.I.; Zykova, T.N.; Sakolova, V.N. Farmakol.
Taksikol. 1972, 35, 466.
4. Metolcsy, G. World Rev. Pest Contr. 1971, 10, 50 (Chem. Abstr. 1972,
76, 82031s).

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5. Sharanin, Yu.A.; Klokol, G.V. Zh. Org. Khim. 1984, 20 (11), 2448.
6. Ibrahim, M.K.A.; El-Moghayar, M.R.H.; Sharaf, M.A.F. Indian J. Chem.
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10. Tu, S.J.; Zhou, J.F.; Lu, Z.S.; Deng, X.; Shi, D.Q.; Wang, S.H. Synth.
Commun. 2002, 19, 3063.
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Commun. 2001, 17, 2675.
12. Tu, S.J.; Zhou, J.F.; Cai, P.J.; Wang, H.; Feng, J.C. Synth. Commun.
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13. Tu, S.J.; Gao, Y.; Guo, C.; Shi, D.Q.; Lu, Z.S. Synth. Commun. 2002, 14,
2137.
14. Tu, S.J.; Zhou, J.F.; Cai, P.J.; Wang, H.; Feng, J.C. Synth. Commun.
2002, 1, 147.
Received in Japan July 28, 2003

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