Microwave promoted efficient synthesis of substituted uracils and thiouracils under solvent-free conditions

Article abstract of DOI:10.1081/SCC-120002693

Several substituted uracils and thiouracils were synthesized in good yields by one-pot condensation reaction of methyl or ethyl β-ketoesters and urea (or thiourea) in solvent-free conditions under microwave irradiation and in short time.

Full text of DOI:10.1081/SCC-120002693

This article was downloaded by: [Illinois State University Milner Library]
On: 04 December 2012, At: 07:35
Publisher: Taylor & Francis
Informa Ltd Registered in England and Wales Registered Number: 1072954 Registered office: Mortimer House,
37-41 Mortimer Street, London W1T 3JH, UK
Synthetic Communications: An International Journal
for Rapid Communication of Synthetic Organic
Chemistry
Publication details, including instructions for authors and subscription information:
http://www.tandfonline.com/loi/lsyc20
MICROWAVE PROMOTED EFFICIENT SYNTHESIS OF
SUBSTITUTED URACILS AND THIOURACILS UNDER
SOLVENT-FREE CONDITIONS
Mohammad M. Mojtahedi a , Mohammad R. Saidi a , Jafar S. Shirzi b & Mohammad
Bolourtchian b
a Department of Chemistry, Sharif University of Technology, Tehran, Iran
b Chemistry and Chemical Engineering Research Center of Iran, Tehran, Iran
Version of record first published: 16 Aug 2006.
To cite this article: Mohammad M. Mojtahedi, Mohammad R. Saidi, Jafar S. Shirzi & Mohammad Bolourtchian (2002):
MICROWAVE PROMOTED EFFICIENT SYNTHESIS OF SUBSTITUTED URACILS AND THIOURACILS UNDER SOLVENT-FREE CONDITIONS,
Synthetic Communications: An International Journal for Rapid Communication of Synthetic Organic Chemistry, 32:6, 851-855
To link to this article: http://dx.doi.org/10.1081/SCC-120002693
PLEASE SCROLL DOWN FOR ARTICLE
Full terms and conditions of use: http://www.tandfonline.com/page/terms-and-conditions
This article may be used for research, teaching, and private study purposes. Any substantial or systematic
reproduction, redistribution, reselling, loan, sub-licensing, systematic supply, or distribution in any form to
anyone is expressly forbidden.
The publisher does not give any warranty express or implied or make any representation that the contents
will be complete or accurate or up to date. The accuracy of any instructions, formulae, and drug doses should
be independently verified with primary sources. The publisher shall not be liable for any loss, actions, claims,
proceedings, demand, or costs or damages whatsoever or howsoever caused arising directly or indirectly in
connection with or arising out of the use of this material.

SYNTHETIC COMMUNICATIONS, 32(6), 851–855 (2002)
MICROWAVE PROMOTED
EFFICIENT SYNTHESIS OF
SUBSTITUTED URACILS AND
THIOURACILS UNDER
SOLVENT-FREE CONDITIONS
Mohammad M. Mojtahedi,1 Mohammad R. Saidi,1,
Jafar S. Shirzi,2 and Mohammad Bolourtchian2
*
1Department of Chemistry, Sharif University of
Technology, Tehran, Iran
2Chemistry and Chemical Engineering Research
Center of Iran, Tehran, Iran
ABSTRACT
Several substituted uracils and thiouracils were synthesized
in good yields by one-pot condensation reaction of methyl
or ethyl b-ketoesters and urea (or thiourea) in solvent-free
conditions under microwave irradiation and in short time.
Uracils and thiouracils are important class of compounds which are
widely used due to their pharmacological properties and inhibitory effect
such as anti-inflammatory and virucidal activities.1 Uracil is a constituent of
RNA. Uracil and its derivatives are best synthesized by in situ oxidative
decarboxylation of the reaction product of malic acid and urea with modest
*Corresponding author.
851
Copyright & 2002 by Marcel Dekker, Inc.
www.dekker.com

852
MOJTAHEDI ET AL.
yields. The reaction involves two components condensation reaction with
low yields, especially, in case of substituted uracils. Another method for the
preparation of uracil is the reaction of b-ketoester with urea, and subsequent
ring closure of the intermediate on treatment with sodium ethoxide.2
Substituted malonic ester derivatives and meldrum’s acid also react
urea or thiourea in two step to yield uracil and thiouracil derivatives.3
The microwave assisted organic transformations, coupled with solvent-
free conditions have attracted much attention due to their enhanced reaction
rate, easier work-up, and in many cases, under solvent-free condition.4–8
In continuation of our research in environmentally benign solvent-free
and microwave assisted conditions,9 we now report an operationally simple
and fast method for the preparation of substituted uracils and thiouracils
by one-pot condensation reaction of methyl or ethyl b-ketoesters and urea
(or thiourea) in solvent-free conditions under microwave irradiation and
in short time, Scheme 1. A commercial microwave oven (900 W) was used
for irradiation of the reaction mixture. All compounds were identified by
means of their NMR and IR spectra.
Scheme 1.
EXPERIMENTAL
1H NMR spectra were recorded in CDCl3 on Bruker AC 80 and
500 MHz spectrometer, using TMS as internal standard. IR spectra were
recorded on Matt Son 1000 Unicam FTIR spectrophotometer. MS spectra
were recorded on Fisons 800 trio.
General procedure for the preparation of uracil and thiouracil. Urea or
thiourea (2.0 mmol) and methyl or ethyl b-ketoesters (2.0 mmol) were mixed
thoroughly in a test tube and were irradiated in conventional microwave

SUBSTITUTED URACILS AND THIOURACILS
853
oven for the given time (Table 1). The mixture melts and after the reaction,
the mixture was washed with water (2 ꢀ 5 ml). Then the solid product was
crystallized from ethanol/water solution.
6-Methyluracil. M.p.>300ꢁC, lit. 311–312ꢁC, (ref. 11, M-03510,
p 4047). IR (KBr) 3100, 3000, 2850, 2800, 1720, 1670, 1650, 1410,
Table 1. Conversion of Diketones to Uracils and Thiouracils

854
MOJTAHEDI ET AL.
1
1340 cmꢂ1. H NMR (DMSO-d6) d 2.03 (s, 3H), 5.33 (s, 1H), 10.9 (br, s,
2H). MS 126 (Mþ, base peak), 83 (32), 68 (61).
6-Methylthiouracil. M.p.>300ꢁC, lit. 326–331ꢁC, (ref. 11, 7th supple-
ment, D-70232, p. 14). IR (KBr) 3118, 2939, 1676, 1561, 1423, 1351, 1242,
1
1170 cmꢂ1. H NMR (DMSO-d6) d 2.1 (s, 3H), 5.6 (s, 1H), 13.3 (br, s, 2H).
13C NMR (DMSO-d6) d 175 (C), 160 (C), 152 (C), 103 (CH), 17 (CH3). MS
142 (Mþ, base peak), 84 (17), 68 (41).
6-Phenyluracil. M.p. 280ꢁC, lit. 282–284ꢁC, (ref. 11, P-01587, p. 4673).
IR (KBr) 3407, 3158, 3014, 2744, 1708, 1671, 1490, 1410, 1284 cmꢂ1
.
1H NMR (DMSO-d6) d 5.3 (s, 1H), 7.5–7.7 (m, 5H), 10.1 (br, s, 2H). MS
188 (Mþ, base peak), 145 (42), 104 (60).
6-Phenylthiouracil. M.p. 263ꢁC, lit. 263–265ꢁC, (ref. 11, D-60268, 6th
supplement, p. 160). IR (KBr) 3130, 3107, 3031, 1671, 1622, 1551, 1464,
1
1249, 1174 cmꢂ1. H NMR (DMSO-d6) d 6.1 (s, 1H), 7.5–7.7 (m, 5H), 12.5
(br, s, 2H). 13C NMR (DMSO-d6) d 176 (C), 160 (C), 152 (C), 131 (C), 129
(CH), 128 (CH), 127 (CH), 103 (CH). MS 204 (Mþ, base peak), 170 (29),
104 (57), 77 (25).
6-Chloromethyluracil. M.p. 257–258ꢁC, IR (KBr) 3161, 3042, 2844,
1702, 1694, 1428, 1287, 826, 744 cmꢂ1 1H NMR (DMSO-d6) d 4.3 (s,
.
2H), 5.6 (s, 1H), 11.1 (br, s, 2H). 13C NMR (DMSO-d6) d 163 (C), 151
(C), 150 (C), 100 (CH), 50 (CH2). MS 160 (Mþ, base peak), 162 {(M þ 2)þ,
(34)}, 125 (33), 112 (34).
5-Ethyl-6-methyluracil. M.p. 245ꢁC, lit. 246–248ꢁC, (ref. 11, E-01051,
p. 2551). IR (KBr) 3116, 2933, 1710, 1665, 1447, 1159 cmꢂ1 1H NMR
.
(DMSO-d6) d 0.9 (t, J ¼ 7 Hz, 3H), 2.2 (s, 3H), 2.3 (q, J ¼ 7 Hz, 2H), 11.0
(br, s, 2H). MS 154 (Mþ, 97), 139 (92), 126 (20), 110 (12), 96 (base peak).
5-Ethyl-6-methylthiouracil. M.p. 218ꢁC, lit. 216–218ꢁC, (ref. 10). IR
.
(KBr) 3116, 2969, 1657, 1560, 1450, 1195 cmꢂ1 1H NMR (DMSO-d6)
d 0.95 (t, J ¼ 7 Hz, 3H), 2.1 (s, 3H), 2.3 (q, J ¼ 7 Hz, 2H), 12.1 (br, s, 2H).
MS 170 (Mþ, base peak), 155 (35), 96 (41).
ACKNOWLEDGMENT
We also thank Iranian National Research Council for partial financial
support.
REFERENCES
1. (a) Smith, D.M. In Comprehensive Organic Chemistry, Sammes, P.G.,
Ed.; Pergamon Press: London, 1979; Vol. 4, p. 86, 90; (b) Skulnick, H.I.;

SUBSTITUTED URACILS AND THIOURACILS
855
Smith, H.; Smith, R.J.; Wierenga, W. U. S. Pat. 4,495,349, CA:
102,185093y, 1985; (c) Skulnick, H.I.; Weed, S.D.; Edison, E.E.;
Renis, H.E.; Stringfellow, D.A. J. Med. Chem. 1985, 28, 1864.
2. (a) Skulnick, H.I.; Ludens; Wendling, M.G.; Glenn, E.M.; Rohloff,
N.A.; Smith, Gedye, R.; Smith, R.J. Wierenga, W. J. Med. Chem.
1985, 28, 1864; (b) Skulnick, H.I.; Wierenga, W. Heterocycles 1986,
29, 1499; (c) Lamon, R.W. J. Heterocycl. Chem. 1986, 5, 837;
(d) Lapucha, A. Synthesis 1987, 256; (d) Vuano, B.M.; Pieroni, O.I.;
Cabaleiro, M.C. J. Chem. Research (S), 2000, 318.
3. Cassis, R.; Tapia, R.; Valderrama, J.A. Synth. Commun. 1984, 14, 961.
4. (a) For reviews see: Abramovitch, R.A. Org. Prep. Proc. Int. 1991, 23,
683; (b) Mingos, D.M.P.; Baghurst, D.R. Chem. Soc. Rev. 1991, 20, 1.
5. Raner, K.D.; Strauss, C.R.; Trainor, R.W.; Thorn, J.S. J. Org. Chem.
1995, 60, 2456.
6. Majetich, G.; Hicks, R.J. Microwave Power and Electromagn. Energy
1995, 30, 27.
7. (a) Varma, R.S.; Dahiya, R. J. Org. Chem. 1998, 63, 9038; (b) Varma,
R.S.; Dahiya, R. Tetrahedron Lett. 1997, 38, 2034; (c) Varma, R.S.;
Saini, R.K.; Dahiya, R. Tetrahedron Lett. 1997, 38, 7823.
8. Sharifi, A.; Mojtahedi, M.M.; Saidi, M.R. Tetrahedron Lett. 1999,
40, 1179.
9. (a) Mojtahedi, M.M. Saidi, M.R.; Bolourtchian, M. J. Chem.
Research (S) 1999, 710; (b) Mojtahedi, M.M.; Sharifi, A.;
Mohsenzadeh, F.; Saidi, M.R. Synth. Commun. 2000, 30, 69.
10. Anderson, G.W. J. Am. Chem. Soc. 1945, 61, 2197.
11. Buckingham, J., Executive Ed. Dictionary of Organic Compounds, 5th
Ed.; Chapman and Hall, 1992.
Received in Japan January 5, 2001