EXPERIMENTAL
Uracil (min. 99%), thymine (min. 99%), allyl bromide (99%), sodium hydride (powder, 95%), and di-
methyl sulfoxide (anhydrous, >99.9%) were purchased from Sigma-Aldrich and used as received. The MWA
reactions were performed on the CEM Discover microwave synthesis reactor, equipped with an IntelVent
controller for pressure release and using Synergy software for control of parameters. NMR spectra were
registered on a Bruker Avance DRX 400 (400 MHz) instrument in DMSO-d as solvent with TMS as internal
6
standard.
MWA Synthesis of Allyl Nucleobases (General Method). A three-necked 25 ml round-bottomed flask,
fitted with anhydrous CaCl protection against moisture and a magnetic stirring bar, is flushed with dry argon and
2
charged with 6 ml dry DMSO. Then, 0.1 g (4 mmol) sodium hydride is added in small portions under inert
atmosphere. The heterogeneous mixture is magnetically stirred at 60°C for 30 min while observing the NaH
consumption. After cooling to room temperature, the nucleobase (2.7 mmol) is added and stirred for another
60 min. Allyl bromide (0.56 g, 4.6 mmol) is added to the resulting solution, which is then transferred under dry,
inert conditions into a 10 ml microwave vial and sealed. The microwave irradiation is performed using the standard
mode of the reactor in two cycles of 60 sec each at 250 W and a constant temperature of 65°C. The resulting
solution is then filtered to remove the NaBr, and the solvent, DMSO, is removed at 1–5 mm Hg by vapor stripping
with a chloroform–toluene (2:1) mixture. The obtained solid is purified by recrystallization from 2-PrOH (uracil
derivative) or toluene (thymine derivative) to afford the final product.
1
1
-(Prop-2-en-1-yl)pyrimidine-2,4(1H,3H)-dione as white solid, yield 88%; mp 101–103°C. H NMR
3
spectrum, δ, ppm (J, Hz): 11.29 (1H, s, H-3); 7.58 (1H, d, J = 8.0, H-6); 5.94–5.85 (1H, m, β-H); 5.59 (1H, d,
3
3
13
J = 8.0, H-5); 5.21–5.11 (2H, m, γ-H
2
); 4.30 (2H, d, J = 6.0, α-H
50.73 (C-2); 145.38 (C-6); 133.05 (C-β); 117.31 (C-γ); 101.14 (C-5); 49.03 (C-α).
-Methyl-1-(prop-2-en-1-yl)pyrimidine-2,4(1H,3H)-dione as pale-yellow solid, yield 87%; mp 96–
2
). C NMR spectrum, δ, ppm: 163.71 (C-4);
1
5
1
9
4
1
9°C. H NMR spectrum, δ, ppm (J, Hz): 10.59 (1H, s, H-3); 7.26 (1H, s, H-6); 5.86–5.77 (1H, m, β-H); 5.10–
3
13
.98 (2H, m, γ-H ); 4.17 (2H, d, J = 6.0, α-H ); 1.73 (3H, s, 5-CH ). C NMR spectrum, δ, ppm: 164.38 (C-4);
2
2
3
3
51.23 (C-2); 143.18 (C-6); 131.88 (C-β); 118.07 (C-γ); 102.34 (C-5); 49.35 (C-α); 11.96 (5-CH ).
REFERENCES
1
2
3
4
5
6
7
8
9
.
.
.
.
.
.
.
.
.
P. Lidström, J. Tierney, B. Wathey, and J. Westman, Tetrahedron, 57, 9225 (2001).
V. V. Namboodiri and R. S. Varma, Green Chem., 3, 146 (2001).
R. S. Varma, Green Chem., 1, 43 (1999).
F. M. Moghaddam, M. Ghaffarzadeh, and S. H. Abdi-Oskoui, J. Chem. Res. (S), 574 (1999).
R. S. Varma, R. K. Saini, and H. M. Meshram, Tetrahedron Lett., 38, 6525 (1997).
M. Melucci, G. Barbarella, and G. Sotgiu, J. Org. Chem., 67, 8877 (2002).
K. D. Raner, C. R. Strauss, F. Vyskoc, and L. Mokbel, J. Org. Chem., 58, 950 (1993).
L. Perreux and A. Loupy, Tetrahedron, 57, 9199 (2001).
M. Chaouchi, A. Loupy, S. Marque, and A. Petit, Eur. J. Org. Chem., 1278 (2002).
C. R. Strauss and R. W. Trainor, Aust. J. Chem., 48, 1665 (1995).
J. C. Burbiel, J. Hockemeyer, and C. E. Müller, Beilstein J. Org. Chem., 2, 20 (2006).
C. O. Kappe, D. Dallinger, and S. S. Murphree, Practical Microwave Synthesis for Organic Chemists,
Wiley-VCH, Weinheim, Germany, 2008.
1
1
1
0.
1.
2.
1
1
1
1
1
3.
4.
5.
6.
7.
A. Loupy (editor), Microwaves in Organic Synthesis, Wiley-VCH, Weinheim, Germany, 2002.
Z. Paryzek and B. Tabaczka, Org. Prep. Proced. Int., 33, 400 (2001).
Y. Tateoka, T. Kimura, K. Watanabe, I. Yamamoto, and I. K. Ho, Chem. Pharm. Bull., 35, 4928 (1987).
V. Malik, P. Singh, and S. Kumar, Tetrahedron, 61, 4009 (2005).
T. Shimizu, R. Iwaura, M. Masuda, T. Hanada, and K. Yase, J. Am. Chem. Soc., 123, 5947 (2001).
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