SHORT PAPER
One-Pot Synthesis of 3,4-Dihydropyrimidin-2(1H)-ones and Thiones
2093
Ravindranath, N.; Venkataih, B. Tetrahedron Lett. 2004, 45,
2425.
hydes. The compatibility with various functional groups,
mild reaction conditions, high yields and application of
inexpensive, mild, readily and easily available iodine as
catalyst are the advantages of the present procedure.
(2) (a) Kappe, C. O. Tetrahedron 1993, 49, 6937. (b)Kappe, C.
O.; Fabian, W. M. F. Tetrahedron 1997, 53, 2803.
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All the aldehydes, 1,3-dicarbonyl compounds and urea or thiourea
were available commercially. I2 was obtained from LOBA Chemi-
cals, India. Melting points were determined in a capillary tube and
are not corrected. The spectra were run on the following instru-
1
ments: IR, Perkin-Elmer (RX1 FT-IR), H NMR: Varian Gemini
(4) (a) Snider, B. B.; Shi, Z. J. Org. Chem. 1993, 58, 3828; and
references cited therein. (b) Overman, L. E.; Robinowitz, M.
H.; Renhowe, P. A. J. Am. Chem. Soc. 1995, 117, 2657; and
references cited therein. (c) Rovnyak, G. C.; Kimball, S. D.;
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Moreland, S. J. Med. Chem. 1995, 38, 119.
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Freyer, J.; De Brosse, C.; Mai, C.; Trunch, A.; Faulkner, D.
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Tetrahedron Lett. 1996, 37, 6977.
200 MHz and EI-MS: VG Micromass 7070 H (70 eV).
Typical Experimental Procedure
A mixture of an aldehyde (2 mmol), 1,3-dicarbonyl compound (2
mmol), urea or thiourea (2.5 mmol) and iodine (100 mg, 0.79 mmol)
in CH3CN (10 mL) was heated under reflux for 6–8 h under N2 at-
mosphere. The reaction was monitored by TLC. After completion
of the reaction the solvent was removed under reduced pressure and
the residue was extracted with EtOAc. The EtOAc extract was
washed with a solution of sodium thiosulfate (2 × 10 mL) and sub-
sequently with water (3 × 10 mL) and dried over anhyd Na2SO4.
Evaporation of the solvent under reduced pressure yielded the solid,
which was crystallized from EtOH to afford the pure compound.
1
(6) Biginelli, P. Gazz. Chim. Ital. 1893, 23, 360.
All the products were characterized from their spectral (IR, H
(7) (a) Atwal, K. S.; Rovnyak, G. C.; O’, R. e. i. l. l. y. B. C.;
Schwartz, J. J. Org. Chem. 1989, 54, 5898; and references
cited therein. (b) Gupta, R.; Gupta, A. K.; Paul, S.; Kachroo,
P. L. Indian J. Chem.: Sect. B 1995, 34, 151.
NMR, and MS) data. The spectral data of the unknown compounds
are given below.
5-Ethoxycarbonyl-6-methyl-4-(3-methoxy,4-hydroxyphenyl)-
3,4-dihydropyrimidin-2(1H)-thione (4o, Entry 15)
Solid; mp 241–242 °C.
IR (KBr): 3245, 2927, 1700, 1645, 1515 cm–1.
1H NMR (CDCl3 + DMSO-d6): d = 8.84 (br s, 1 H), 8.30 (br s, 1 H),
7.18 (br s, 1 H), 6.88–6.62 (m, 3 H), 5.12 (d, J = 2.5 Hz, 1 H), 4.01
(q, J = 7.0 Hz, 2 H), 3.80 (s, 3 H), 2.21 (s, 3 H), 1.08 (t, J = 7.0 Hz,
3 H).
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Wang, J. T.; Peppe, C. Tetrahedron 2002, 58, 4801.
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(g) Ramalinga, K.; Vijayalakshmi, P.; Kaimal, T. N. B.
Synlett 2001, 863. (h) Varala, R.; Alam, M. M.; Adapa, S. R.
Synlett 2003, 67. (i) Gourhari, M.; Pradip, K.; Chandrani, G.
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FAB–MS: m/z = 323 [M+ + 1].
5-Methoxycarbonyl-6-methyl-4-(isopropyl)-3,4-dihydropyrim-
idin-2(1H)-thione (4a¢, Entry 27)
Solid; mp 176–177 °C.
IR (KBr): 3236, 3108, 1702, 1647 cm–1.
1H NMR (CDCl3 + DMSO-d6): d = 8.68 (br s, 1 H), 6.76 (br s, 1 H),
4.18 (d, J = 3.0 Hz, 1 H), 3.62 (s, 3 H), 2.27 (s, 3 H), 1.78 (m, 1 H),
0.90 (d, J = 6.0 Hz, 3 H), 0.80 (d, J = 6.0 Hz, 3 H).
FAB–MS: m/z = 229 [M+ + 1].
5-Ethoxycarbonyl-6-methyl-4-(pentyl)-3,4-dihydropyrimidin-
2(1H)-thione (entry 4c¢, Entry 29)
Solid; mp 167–168 °C.
IR (KBr): 3272, 3060, 1685, 1623 cm–1.
1H NMR (CDCl3 + DMSO-d6): d = 8.18 (br s, 1 H), 5.72 (br s, 1 H),
4.08–4.38 (m, 3 H), 2.30 (s, 3 H), 1.18–1.62 (m, 11 H), 0.94 (t, J =
7.0 Hz, 3 H).
FAB–MS: m/z = 271 [M+ + 1].
Acknowledgment
The authors thank CSIR, New Delhi and IICT for financial assi-
stance.
(11) Van den Eynde, J. J.; Audiart, N.; Canonne, V.; Michel, S.;
Van Haverbeke, Y.; Kappe, C. O. Heterocycles 1997, 45,
1967.
References
(1) Part 35 in the series, ‘Studies on Novel Synthetic
Methodologies’. For part 34 see: Das, B.; Banerjee, J.;
Synthesis 2004, No. 13, 2091–2093 © Thieme Stuttgart · New York