Facile aza-Michael additions of uracil derivatives to acrylates

Article abstract of DOI:10.3184/174751912X13282923623804

24 Aza-Michael adducts were synthesised in moderate to excellent yields by the addition of 5-substituted uracils to acrylates with ethylamine as a catalyst. Many of the adducts were obtained in almost quantitive yield without column chromatography. The procedure provideded an efficient approach to the synthesis of N-1 uracil adducts using acrylates as acceptors. The structures of the compounds were determined by ¹H NMR, ¹³C NMR, mass spectra and X-ray crystallography analyses. The uracil unit is present in DNA and related natural products and has a broad spectrum of biological activity.

Full text of DOI:10.3184/174751912X13282923623804

114 RESEARCH PAPER
FEBRUARY, 114–117
JOURNAL OF CHEMICAL RESEARCH 2012
Facile aza-Michael additions of uracil derivatives to acrylates
Shuguang Zhou, Mingxia Xu, Siyu Ye, Dashuai Li, Jing Xu, Pei Mao and Jing Xiong*
College of Chemistry and Materials Engineering, Wenzhou University, Wenzhou, 325027, P. R. China
24 Aza-Michael adducts were synthesised in moderate to excellent yields by the addition of 5-substituted uracils to
acrylates with ethylamine as a catalyst. Many of the adducts were obtained in almost quantitive yield without column
chromatography. The procedure provideded an efficient approach to the synthesis of N-1 uracil adducts using acry-
lates as acceptors. The structures of the compounds were determined by 1H NMR, 13C NMR, mass spectra and X-ray
crystallography analyses. The uracil unit is present in DNA and related natural products and has a broad spectrum of
biological activity.
Keywords: uracil derivatives, acrylates, aza-Michael addition, crystal structure
Uracil and its derivatives are of interest because the uracil unit
is present in DNA and related natural products.1,2 Uracils are
privileged structures in drug discovery and display a broad
spectrum of biological activity.3–5 For example, 5-nitrouracil
and its derivatives exhibit antiviral effects because they are
inhibitors of thymidylate synthetase.5 5-Fluorouracil and its
derivatives are widely used for the treatment of cancers6–8 and
1-cyanomethyl 5-halogenouracils were active against P-388/s,
FM-3A/s and U-937/s cell lines.9 Recently, several methods
for the modification of uracil and its derivatives have been
developed.10–13 The functionalisations of uracil derivatives at
the N-1 or N-3 position are of importance. The Michael-
type addition (in this case aza-Michael reaction) is one of the
most common strategies for the synthsis of N-alkylated uracils
and their precursors and it is also one of the convenient
synthetic approaches towards the formation of an exocyclic
C–N bond.14–18
Continuing our research interest on the modification of
uracil and its 5-substituted derivatives at the N-1 position,19 we
now report the study of the Michael-type addition of uracil
anions to acceptors possessing activated double bonds, e.g.,
acrylic esters. As shown in Scheme 1, N-1 monoadducts could
be prepared when uracil or 5-substituted uracils are used as
Michael donors, and reacted with acrylic esters in the presence
of triethylamine. In addition, the common methods of purifica-
tion by column chromatography and recrystallisation were not
necessary for many of examples.
aza-Michael addition of aromatic amines to α,β-unsaturated
ketones which proceeded without any catalyst or solvent, 17 no
adduct was formed in this reaction without a catalyst. The
yield increased significantly when triethylamine was added in
(entries 9 and 10). We then changed the catalyst to K2CO3
or ammonia instead of triethylamine. The yield improved
from 50% to 80% when the reaction carried out from 40 °C to
100 °C in DMF.
Using the optimal condition, we then investigated the
reaction of uracil and other 5-substituted uracils. As seen from
Table 2, the reaction offered moderate to excellent yields.
Among the 5-substituted uracils selected, those bearing the
chloro-(1c), bromo-(1d), iodo-(1e), methyl-(1h) substituent
reacted with methyl acrylate (2a) to give the corresponding
pure products without column chromatography or recrystalli-
sation. Similar results were obtained when ethyl acrylate(2b)
or butyl acrylate(2c) was used as a substrate. However, when
5-nitrouracil (1g) was utilised, the corresponding adducts
were obtained in lower yields maybe because of the poor
nucleophilicity of the substrate.
1
All the adducts were characterised by H NMR,13C NMR
and MS. In order to confirm the structure of compound 3,
the crystal structure of 3e as a representative example was
determined by X-ray crystallography. An ORTEP view of the
molecule together with the atom numbering is shown in Fig. 1,
the crystal data and structure refinement is shown in Table 3.
In conclusion, 24 aza-Michael adducts have been synthe-
sised from uracil or 5-substituted uracil derivatives and
acrylates, the crystal structure of 3e was determined by X-ray
diffraction analysis. The biological activity of the above
adducts is being investigation in our laboratory.
Results and discussion
Initially, we selected a trial reaction using 1: 1.2 M ratio of
5-fluorouracil (1b) and methyl acrylate (2a), 0.1 mmol trieth-
ylamine as a catalyst in order to optimise the solvent, and the
temperature range from room temperature to 60 °C, DMF gave
the best result. The reaction proceeded smoothly in DMF to
give 3b in 95% yield (Table 1, entry 8). We subsequently
screened the temperature, from 60 °C to 100 °C, and found
that the yield stabilised at 95% in DMF after 60 °C. Unlike the
Experimental
All chemicals were purchased from Aladdin chemical companies.
The progress of the reactions was detected by TLC using silica gel GF
254 plates. Melting points were recorded on a Digital Melting Point
Appatatus WRS-1B and are uncorrected. 1H NMR (500 MHz) and 13
C
Scheme 1
* Correspondent. E-mail: xiongjing@wzu.edu.cn

JOURNAL OF CHEMICAL RESEARCH 2012 115
Table 1 Optimisation of aza–Michael reaction of 1b with 2a
Entry
Solvent
Yield/%
1
2
Ethyl acetate
CH3CN
48
67
61
22
44
34
56
95
65
50
3
THF
4
Toluene
1,4-dioxane
Acetone
Ethanol
DMF
H2O
Solvent free
5
6
7
8
9
10
Fig. 1 The molecular structure of 3e.
Table 3 Crystal data and structure refinement for 3e
Table
2
Aza-Michael addition of 5-substituted uracils to
Empirical formula
C8 H9 I N2 O4
methyl acrylate in DMF at 60 °C
Formula weight
Temperature
Wavelength
Crystal system
space group
Volume
324.07
Entry
Substituted uracils
Product
Yield
/%
298(2) K
0.71073 Å
Monoclinic
P 21/c
1099.7(2) Å
4
1
2
Uracil
3a
3b
86
95
Z
Calculated density
Unit cell dimensions
1.957 Mg m−3
a = 11.1572(12) Å,
b = 8.1666(9) Å
c = 12.0789(14) Å
α = 90 °, β = 92.300(2) °, γ = 90°
2.909
5-Fluorouracil
µ(mm−1)
F(000)
3
4
5
6
7
8
5-Chlorouracil
5-Bromouracil
5-Iodouracil
3c
3d
3e
93
97
92
88
71
95
624
–13≤ h ≤13
–9≤ k ≤9
–14≤ l ≤14
0.1316
1.043
Index ranges
wR2
Goodness-of-fit on F2
obtained after distillation of the DMF, and removal of excessive
acrylic ester with ethyl acetate or ether under reduced pressure.
3-(2,4-Dioxo-3,4-dihydro-2H- pyrimidin-1-yl)-propionic acid methyl
5-Hydroxymethyluracil 3f
1
ester (3a): Yield 86%, m.p. 133.2–134.9 °C; H NMR (500 MHz,
DMSO-d6) δ 11.25 (s, 1H), 7.63 (d, 1H, J = 7.5 Hz), 5.54 (d, 1H,
J = 7.5 Hz), 3.89 (t, 2H, J = 7.0 Hz), 3.61 (s, 3H), 2.70 (t, 2H, J =
7.0 Hz); 13C NMR (125 MHz, DMSO-d6) δ 171.4, 163.9, 151.0, 146.2,
100.9, 51.7, 44.2, 32.7. ESI-MS m/z: 199 [M+H]+. Anal. Calcd for
C8H10N2O4: C, 48.48; H, 5.09; N, 14.14. Found: C, 48.42; H, 5.03; N,
14.22%.
5-Nitrouracil
3g
3h
3-(5-Fluoro-2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-propionic
acid methyl ester (3b): Yield 95%, m.p. 153.3–153.8 °C; H NMR
5-Methyluracil
1
(500 MHz, DMSO-d6) δ 11.78 (s, 1H), 8.05 (d, 1H, JFH = 7.0 Hz), 3.86
(t, 2H, J = 7.0 Hz), 3.61 (s, 3H), 2.72 (t, 2H, J = 7.0 Hz); 13C NMR
(125 MHz, DMSO-d6) δ 171.4, 157.6 (d, 2JCF = 25.5 Hz), 149.7, 139.5
(d, JCF = 227.1 Hz), 130.7 (d, JCF = 33.3 Hz), 51.7, 44.3, 32.4.
ESI-MS m/z: 217 [M+H]+. Anal. Calcd for C8H9FN2O4: C, 44.45; H,
4.20; N, 12.96. Found: C, 44.62; H, 4.14; N, 13.01%.
The corresponding ethyl and butyl esters are described in the
experimental section.
1
2
3-(5-Chloro-2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-propionic
acid methyl ester (3c): Yield 95%; m.p. 157.1–158.4 °C; H NMR
(500 MHz, DMSO-d6) δ 11.79 (s, 1H), 8.10 (s, 1H), 3.90 (t, 2H,
J = 7.0 Hz), 3.58 (s, 3H), 2.72 (t, 2H, J = 7.0 Hz); 13C NMR (125 MHz,
DMSO-d6) δ 171.4, 159.7, 150.2, 143.5, 106.0, 51.7, 44.5, 32.4.
ESI-MS m/z: 233 [M+H]+. Anal. Calcd for C8H9ClN2O4: C, 41.31; H,
3.90; N, 12.04. Found: C, 41.40; H, 3.96; N, 11.93%.
NMR (125 MHz) analyses were recorded on a Bruker AVANCE 500
spectrometer in DMSO-d6 with TMS as internal standard. Elemental
analyses were using a Carlo-Erba 1112 elemental analyser. Mass
spectra were obtained on a DECAX-30000 LCQ DecaXP Plus
instrument. The crystallographic data were collected on a Bruker
Smart-Apex CCD diffractometer.
1
3-(5-Bromo-2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-propionic
acid methyl ester (3d): Yield 97%; m.p. 163.3–164.9 °C ; H NMR
Synthesis of compound 3; general procedure
1
Uracil or 5-substituted uracil (10 mmol), acrylic ester (12 mmol),
triethylamine (0.1 mmol) and DMF 20 mL were added into a flask and
stirred at 60 °C for 2–4 hours with TLC detection. The solid 3 was
(500 MHz, DMSO-d6) δ 11.77 (s, 1H), 8.19 (s, 1H), 3.92 (t, 2H,
J = 7.0 Hz), 3.60 (s, 3H), 2.73 (t, 2H, J = 7.0 Hz); 13C NMR (125 MHz,

116 JOURNAL OF CHEMICAL RESEARCH 2012
DMSO-d6) δ 171.4, 159.8, 150.4, 145.9, 94.5, 51.7, 44.4, 32.5.
ESI-MS m/z: 277 [M+H]+. Anal. Calcd for C8H9BrN2O4: C, 34.68; H,
3.27; N, 10.11. Found: C, 34.45; H, 3.21; N, 10.17%.
NMR (500 MHz, DMSO-d6) δ 11.28 (s, 1H), 7.52 (s, 1H), 4.95 (t, 1H,
J = 5.0 Hz), 4.13 (d, 2H, J = 5.0 Hz), 4.06 (q, 2H, J = 7.0 Hz), 3.91 (t,
2H, J = 6.5 Hz), 2.67 (t, 2H, J = 6.5 Hz), 1.17 (t, 3H, J = 7.0 Hz); 13
C
3-(5-Iodo-2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-propionic
acid methyl ester (3e): Yield 92%; m.p. 185.6–187.3 °C; H NMR
NMR (125 MHz, DMSO-d6) δ 170.9, 163.3, 150.9, 142.3, 113.4, 60.4,
56.0, 44.2, 33.1, 14.1. ESI-MS m/z: 243 [M+H]+. Anal. Calcd for
C10H14N2O5: C, 49.58; H, 5.83; N, 11.56. Found: C, 49.65; H, 5.86; N,
11.69%.
1
(500 MHz, DMSO-d6) δ 11.61 (s, 1H), 8.15 (s, 1H), 3.90 (t, 2H,
J = 7.0 Hz), 3.59 (s, 3H), 2.70 (t, 2H, J = 7.0 Hz); 13C NMR (125 MHz,
DMSO-d6) δ 171.3, 161.2, 150.7, 150.5, 67.9, 51.7, 44.2, 32.5.
ESI-MS m/z: 325 [M+H]+. Anal. Calcd for C8H9IN2O4: C, 29.65; H,
2.80; N, 8.64. Found: C, 29.50; H, 2.85; N, 8.56%.
3-(5-Hydroxymethyl-2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-
propionic acid methyl ester (3f): Yield 88%; m.p. 136.7–139.5 °C; 1H
NMR (500 MHz, DMSO-d6) δ 11.28 (s, 1H), 7.53 (s, 1H), 4.96 (t, 1H,
J = 5.0 Hz), 4.13 (d, 2H, J = 5.0 Hz), 3.92 (t, 2H, J = 7.0 Hz), 3.61 (s,
3H), 2.70 (t, 2H, J = 7.0 Hz); 13C NMR (125 MHz, DMSO-d6) δ 171.4,
163.4, 150.9, 150.5, 142.3, 113.4, 56.0, 51.7, 44.2, 32.9. ESI-MS m/z:
229 [M+H]+. Anal. Calcd for C9H12N2O5: C, 47.37; H, 5.30; N, 12.28.
Found: C, 47.54; H, 5.38; N, 12.22%.
3-(5-Nitro-2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-propionic
1
acid ethyl ester (3o): Yield 79%; m.p. 162.5–163.7 °C; H NMR
(500 MHz, DMSO-d6) δ 12.03 (s, 1H), 9.26 (s, 1H), 4.09 (d, 2H,
J = 6.5 Hz), 4.06 (q, 2H, J = 7.0 Hz), 2.76 (t, 2H, J = 6.5 Hz), 1.18 (t,
3H, J = 7.0 Hz); 13C NMR (125 MHz, DMSO-d6) δ 170.8, 155.2,
151.5, 149.4, 124.8, 60.5, 45.5, 32.4, 14.1. ESI-MS m/z: 258 [M+H]+.
Anal. Calcd for C9H11N3O6: C, 42.03; H, 4.31; N, 16.34. Found: C,
42.35; H, 4.26; N, 16.23%.
3-(5-Methyl-2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-propionic
1
acid ethyl ester (3p): Yield 99%; m.p. 154.6–155.1 °C; H NMR
(500 MHz, DMSO-d6) δ 11.23 (s, 1H), 7.51 (s, 1H), 4.07 (q, 2H,
J = 7.0 Hz), 3.87 (t, 2H, J = 7.0 Hz), 2.68 (t, 2H, J = 7.0 Hz), 1.75 (s,
3H), 1.17 (t, 3H, J = 7.0 Hz); 13C NMR (125 MHz, DMSO-d6) δ 170.9,
164.4, 151.0, 141.9, 108.4, 60.3, 44.0, 33.0, 14.1, 12.0. ESI-MS m/z:
227 [M+H]+. Anal. Calcd for C10H14N2O4: C, 53.09; H, 6.24; N, 12.38.
Found: C, 53.23; H, 6.16; N, 12.30%.
3-(2,4-Dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-propionic acid butyl
ester (3q): Yield 87%, m.p. 77.0–77.9 °C; 1H NMR (500 MHz,
DMSO-d6) δ 11.25 (s, 1H), 7.62 (d, 1H, J = 8.0 Hz), 5.54 (dd, 1H,
J = 8.0, 2.0 Hz), 4.02 (t, 2H, J = 6.5 Hz), 3.90 (t, 2H, J = 6.5Hz), 2.70
(t, 2H, J = 6.5 Hz), 1.56–1.51 (m, 2H), 1.34–1.27 (m, 2H), 0.88 (t, 3H,
J = 7.5 Hz); 13C NMR (125 MHz, DMSO-d6) δ 171.0, 163.9, 151.0,
146.1, 100.8, 64.1, 44.2, 32.9, 30.3, 18.7, 13.6. ESI-MS m/z: 241
[M+H]+. Anal. Calcd for C11H16N2O4: C, 54.99; H, 6.71; N, 11.66.
Found: C, 54.83; H, 6.65; N, 11.74%.
3-(5-Fluoro-2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-propionic
acid butyl ester (3r): Yield 90%, m.p. 71.9–72.3 °C; 1H NMR
(500 MHz, DMSO-d6) δ 11.78 (s, 1H), 8.05 (d, 1H, JFH = 6.5 Hz), 4.03
(t, 2H, J = 7.0 Hz), 3.86 (t, 2H, J = 6.5 Hz), 2.71 (t, 2H, J = 6.5 Hz),
1.57–1.51 (m, 2H), 1.34–1.27 (m, 2H), 0.88 (t, 3H, J = 7.0 Hz); 13C
NMR (125 MHz, DMSO-d6) δ 170.9, 157.6 (d, 2JCF = 25.6 Hz), 149.6,
139.5 (d, 1JCF = 227.1 Hz), 130.6 (d, 2JCF = 33.3 Hz), 64.1, 44.3, 32.6,
30.3, 18.7, 13.6. ESI-MS m/z: 259 [M+H]+. Anal. Calcd for
C11H15FN2O4: C, 51.16; H, 5.85; N, 10.85. Found: C, 51.03; H, 5.92;
N, 10.98%.
3-(5-Nitro-2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-propionic
1
acid methyl ester (3g): Yield 71%; m.p. 151.8–153.3 °C; H NMR
(500 MHz, DMSO-d6) δ 12.03 (s, 1H), 9.26 (s, 1H), 4.08 (t, 2H,
J = 7.0 Hz), 3.61 (s, 3H), 2.79 (t, 2H, J = 7.0 Hz); 13C NMR (125 MHz,
DMSO-d6) δ 171.3, 155.2, 151.5, 149.4, 124.8, 51.8, 45.5, 32.1.
ESI-MS m/z: 244 [M+H]+. Anal. Calcd for C8H9N3O6: C, 39.51; H,
3.73; N, 17.28. Found: C, 39.34; H, 3.77; N, 17.35%.
3-(5-Methyl-2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-propionic
1
acid methyl ester (3h): Yield 95%; m.p. 126.7–127.5 °C; H NMR
(500 MHz, DMSO-d6) δ 11.23 (s, 1H), 7.51 (s, 1H), 3.86 (t, 2H,
J = 7.0 Hz), 3.61 (s, 3H), 2.70 (t, 2H, J = 7.0 Hz), 1.75 (s, 3H); 13C
NMR (125 MHz, DMSO-d6) δ 171.4, 164.4, 151.0, 141.8, 108.4, 51.7,
43.9, 32.8, 12.1. ESI-MS m/z: 213 [M+H]+.Anal. Calcd for C9H12N2O4:
C, 50.94; H, 5.70; N, 13.20. Found: C, 50.75; H, 5.64; N, 13.28%.
3-(2,4-Dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-propionic acid ethyl
1
ester (3i): Yield 83%, m.p. 101.3–101.6 °C; H NMR (500 MHz,
DMSO-d6) δ 11.24 (s, 1H), 7.63 (d, 1H, J = 8.0 Hz), 5.54 (d, 1H,
J = 8.0 Hz), 4.06 (q, 2H, J = 7.0 Hz), 3.89 (t, 2H, J = 7.0 Hz), 2.68
(d, 2H, J = 7.0 Hz), 1.17 (t, 3H, J = 7.0 Hz); 13C NMR (125 MHz,
DMSO-d6) δ 170.9, 163.9, 151.0, 146.2, 100.8, 60.4, 44.2, 32.9, 14.1.
ESI-MS m/z: 213 [M+H]+. Anal. Calcd for C9H12N2O4: C, 50.94; H,
5.70; N, 13.20. Found: C, 50.80; H, 5.65; N, 13.23%.
3-(5-Fluoro-2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-propionic
1
acid ethyl ester (3j): Yield 93%, m.p. 133.5–134.0 °C; H NMR
(500 MHz, DMSO-d6) δ 11.78 (s, 1H), 8.06 (d, 1H, JFH = 7.0 Hz), 4.07
(dq, 2H, J = 7.0, 1.5 Hz), 3.86 (t, 2H, J = 7.0 Hz), 2.70 (t, 2H, J =
7.0 Hz), 1.18 (dt, 3H, J = 7.0, 1.5 Hz); 13C NMR (125 MHz,
3-(5-Chloro-2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-propionic
acid butyl ester (3s): Yield 95%, m.p. 93.9–95.2 °C; 1H NMR
(500 MHz, DMSO-d6) δ 11.81 (s, 1H), 8.12 (s, 1H), 4.03 (t, 2H,
J = 6.5 Hz), 3.91 (t, 2H, J = 7.0 Hz), 2.72 (t, 2H, J = 7.0 Hz), 1.56–
1.51 (m, 2H), 1.34–1.27 (m, 2H), 0.88 (t, 3H, J = 6.5 Hz); 13C NMR
(125 MHz, DMSO-d6) δ 170.9, 159.6, 150.2, 143.5, 106.0, 64.1, 44.5,
32.7, 30.3, 18.7, 13.7. ESI-MS m/z: 275 [M+H]+. Anal. Calcd for
C11H15ClN2O4: C, 48.10; H, 5.50; N, 10.20. Found: C, 48.32; H, 5.54;
N, 10.13%.
DMSO-d6) δ 170.8, 157.6 (d, 2JCF = 25.6 Hz), 149.7, 139.5 (d, 1JCF
=
2
227.1 Hz), 130.7 (d, JCF = 33.4 Hz), 60.4, 44.3, 32.7, 14.1. ESI-MS
m/z: 231 [M+H]+. Anal. Calcd for C9H11FN2O4: C, 46.96; H, 4.82; N,
12.17. Found: C, 46.80; H, 4.85; N, 12.25%.
3-(5-Chloro-2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-propionic
1
acid ethyl ester (3k): Yield 96%, m.p. 159.6–160.0 °C; H NMR
(500 MHz, DMSO-d6) δ 11.80 (s, 1H), 8.12 (s, 1H), 4.07 (q, 2H,
J = 7.0 Hz), 3.91 (t, 2H, J = 7.0 Hz), 2.71 (t, 2H, J = 7.0 Hz), 1.18 (t,
3H, J = 7.0 Hz); 13C NMR (125 MHz, DMSO-d6) δ 170.8, 159.7,
150.2, 143.6, 106.0, 60.4, 44.5, 32.7, 14.1. ESI-MS m/z: 247 [M+H]+.
Anal. Calcd for C9H11ClN2O4: C, 43.83; H, 4.50; N, 11.36. Found: C,
43.67; H, 4.55; N, 11.42%.
3-(5-Bromo-2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-propionic
acid butyl ester (3t): Yield 98%, m.p. 122.4–122.8 °C; H NMR
1
(500 MHz, DMSO-d6) δ 11.77 (s, 1H), 8.18 (s, 1H), 4.02 (t, 2H,
J = 6.5 Hz), 3.92 (t, 2H, J = 6.5 Hz), 2.72 (t, 2H, J = 6.5 Hz), 1.56–
1.51 (m, 2H), 1.34–1.27 (m, 2H), 0.88 (t, 3H, J = 6.5 Hz); 13C NMR
(125 MHz, DMSO-d6) δ 170.9, 159.8, 150.4, 145.9, 94.5, 64.1, 44.5,
32.7, 30.3, 18.7, 13.7. ESI-MS m/z: 319 [M+H]+. Anal. Calcd for
C11H15BrN2O4: C, 41.40; H, 4.74; N, 8.78. Found: C, 41.64; H, 4.69;
N, 8.65%.
3-(5-Bromo-2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-propionic
1
acid ethyl ester (3l): Yield 99%, m.p. 160.1–160.6 °C; H NMR
(500 MHz, DMSO-d6) δ 11.77 (s, 1H), 8.19 (s, 1H), 4.07 (q, 2H,
J = 7.0 Hz), 3.92 (t, 2H, J = 7.0 Hz), 2.71 (t, 2H, J = 7.0 Hz), 1.18 (t,
3H, J = 7.0 Hz); 13C NMR (125 MHz, DMSO-d6) δ 170.8, 159.8,
150.4, 146.0, 94.4, 60.4, 44.5, 32.7, 14.2. ESI-MS m/z: 291 [M+H]+.
Anal. Calcd for C9H11BrN2O4: C, 37.13; H, 3.81; N, 9.62. Found: C,
37.35; H, 3.85; N, 9.58%.
3-(5-Iodo-2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-propionic
1
acid butyl ester (3u): Yield 90%, m.p. 142.9–143.3 °C; H NMR
(500 MHz, DMSO-d6) δ 11.63 (s, 1H), 8.15 (s, 1H), 4.02 (t, 2H,
J = 7.0 Hz), 3.91 (t, 2H, J = 6.5 Hz), 2.70 (t, 2H, J = 6.5 Hz), 1.56–
1.51 (m, 2H), 1.34–1.28 (m, 2H), 0.88 (t, 3H, J = 7.0 Hz); 13C NMR
(125 MHz, DMSO-d6) δ 170.9, 159.8, 150.4, 145.9, 94.5, 64.1, 44.5,
32.7, 30.3, 18.7, 13.7. ESI-MS m/z: 367 [M+H]+. Anal. Calcd for
C11H15IN2O4: C, 36.08; H, 4.13; N, 7.65. Found: C, 36.24; H, 4.19; N,
7.82%.
3-(5-Iodo-2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-propionic
1
acid ethyl ester (3m): Yield 91%; m.p. 153.5–155.0 °C; H NMR
(500 MHz, DMSO-d6) δ 11.64 (s, 1H), 8.17 (s, 1H), 4.06 (q, 2H,
J = 7.0 Hz), 3.92 (t, 2H, J = 7.0 Hz), 2.70 (t, 2H, J = 7.0 Hz), 1.18 (t,
3H, J = 7.0 Hz); 13C NMR (125 MHz, DMSO-d6) δ 170.8, 161.2,
150.7, 150.5, 67.8, 60.4, 44.3, 32.8, 14.2. ESI-MS m/z: 339 [M+H]+.
Anal. Calcd for C9H11IN2O4: C, 31.97; H, 3.28; N, 8.29. Found: C,
31.92; H, 3.25; N, 8.48%.
3-(5-hydroxymethyl-2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-
1
propionic acid butyl ester (3v): Yield 85%; m.p. 94.9–95.4 °C; H
NMR (500 MHz, DMSO-d6) δ 11.28 (s, 1H), 7.52 (s, 1H), 4.95 (t, 1H,
J = 5.0 Hz), 4.13 (d, 2H, J = 5.0 Hz), 4.02 (t, 2H, J = 7.0 Hz), 3.91 (t,
2H, J = 7.0 Hz), 2.69 (t, 2H, J = 7.0 Hz), 1.56–1.51 (m, 2H), 1.34–1.26
(m, 2H), 0.87 (t, 3H, J = 7.0 Hz); 13C NMR (125 MHz, DMSO-d6)
3-(5-hydroxymethyl-2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-
propionic acid ethyl ester (3n): Yield 85%; m.p. 124.1–124.5 °C; 1H

JOURNAL OF CHEMICAL RESEARCH 2012 117
δ 170.9, 163.3, 150.9, 142.2, 113.4, 64.1, 56.0, 44.3, 33.1, 30.3, 18.7,
13.7. ESI-MS m/z: 271 [M+H]+. Anal. Calcd for C12H18N2O5: C, 53.33;
H, 6.71; N, 10.36. Found: C, 53.62; H, 6.78; N, 10.51%.
The CIF file has been deposited with the Cambridge Crystallo-
graphic Data Centre. Supplementary data are available from the CCDC,
on request, quoting the deposition number 838253. NMR spectra of
the compounds are available directly from the correspondent.
3-(5-Nitro-2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-propionic
1
acid butyl ester (3w): Yield 75%; m.p. 155.5–156.5 °C; H NMR
(500 MHz, DMSO-d6) δ 12.04 (s, 1H), 9.26 (s, 1H), 4.09 (t, 2H,
J = 6.5 Hz), 4.03 (t, 2H, J = 6.5 Hz), 2.78 (t, 2H, J = 6.5 Hz), 1.57–
1.52 (m, 2H), 1.35–1.27 (m, 2H), 0.88 (t, 3H, J = 7.5 Hz); 13C NMR
(125 MHz, DMSO-d6) δ 170.9, 155.2, 151.5, 149.4, 124.8, 64.2, 45.6,
32.4, 30.3, 18.8, 13.7. ESI-MS m/z: 286 [M+H]+. Anal. Calcd for
C11H15N3O6: C, 46.32; H, 5.30; N, 14.73. Found: C, 46.50; H, 5.36; N,
14.82%.
3-(5-Methyl-2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-propionic
acid butyl ester (3x): Yield 94%; m.p. 90.5–90.9 °C; 1H NMR
(500 MHz, DMSO-d6) δ 11.23 (s, 1H), 7.50 (s, 1H), 4.02 (t, 2H,
J = 6.5 Hz), 3.87 (t, 2H, J = 7.0 Hz), 2.69 (t, 2H, J = 7.0 Hz), 1.75 (s,
3H), 1.56–1.50 (m, 2H), 1.34–1.26 (m, 2H), 0.87 (t, 3H, J = 7.0 Hz);
13C NMR (125 MHz, DMSO-d6) δ 170.9, 164.4, 150.9, 141.9, 108.4,
64.0, 44.0, 33.0, 30.3, 18.7, 13.6, 12.0. ESI-MS m/z: 255 [M+H]+.
Anal. Calcd for C12H18N2O4: C, 56.68; H, 7.13; N, 11.02. Found: C,
56.87; H, 7.10; N, 11.08%.
We gratefully acknowledge financial support by Zhejiang
Provincial Technology Innovation Project Foundation (No.
2010R424013, No. 2010R424046), and Wenzhou Techonlogy
Project Foundation (No. Y20100003).
Received 30 November 2011; accepted 20 January 2012
Paper 1101018 doi: 10.3184/174751912X13282923623804
Published online: 23 February 2012
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Compound (3e): C8H9IN2O4, M 324.07, T 298(2) K; monoclinic;
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