New strategy for the synthesis of 1,3-disubstituted uracils

Article abstract of DOI:10.1080/00397910701863772

A new strategy for the synthesis of 1,3-disubstituted uracils has been developed. The 1,3-disubstituted uracils were synthesized with good yields by amino-selenenylation of α,β-unsaturated esters and cyclization with isocyanates, followed by oxidation-eli

Full text of DOI:10.1080/00397910701863772

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New Strategy for the Synthesis
of 1,3-Disubstituted Uracils
Jian Cao a & Xian Huang a b
a Department of Chemistry, Zhejiang University ,
Hangzhou, China
b State Key Laboratory of Organometallic Chemistry,
Shanghai Institute of Organic Chemistry, Chinese
Academy of Sciences , Shanghai, China
Published online: 22 Dec 2008.
To cite this article: Jian Cao & Xian Huang (2008) New Strategy for the Synthesis
of 1,3-Disubstituted Uracils, Synthetic Communications: An International Journal
for Rapid Communication of Synthetic Organic Chemistry, 39:2, 205-214, DOI:
10.1080/00397910701863772
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Synthetic Communications1, 39: 205–214, 2009
Copyright # Taylor & Francis Group, LLC
ISSN: 0039-7911 print=1532-2432 online
DOI: 10.1080/00397910701863772
New Strategy for the Synthesis of
1,3-Disubstituted Uracils
Jian Cao1 and Xian Huang1,2
1Department of Chemistry, Zhejiang University, Hangzhou, China
2State Key Laboratory of Organometallic Chemistry, Shanghai Institute
of Organic Chemistry, Chinese Academy of Sciences, Shanghai, China
Abstract: A new strategy for the synthesis of 1,3-disubstituted uracils has been
developed. The 1,3-disubstituted uracils were synthesized with good yields by
amino-selenenylation of a,b-unsaturated esters and cyclization with isocyanates,
followed by oxidation–elimination of the phenylseleno group.
Keywords: a-Phenylseleno-b-amino ester, dihydrouracil, oxidation–elimination,
uracil
Analogs of nucleosides have been successfully used as antineoplastic and
antiviral agents.[1] In this particular area, much attention has been
devoted to the preparation of nucleosides with pyrimidinic bases and
their derivatives, especially uracils. Uracils are an important class of
heterocycles because of their applications as bioactive compounds such
as 5-iodouridine,[2a] (S)-will-ardiine,[2b] zidovudine,[2c] and tifluridine.[1]
Among them, uracils with substi-tuents at N-1 and N-3 are attractive
because of their special biological properties.[2c,3a–c] Although methods
for the preparation of uracils have been widely studied,[4] to the best of
our knowledge, there are few general methods for the synthesis of uracils
with different substituents at N-1 and N-3.
Received in the U.K. August 3, 2007.
Address correspondence to Xian Huang, Department of Chemistry, Zhejiang
University (Campus Xixi), Hangzhou 310028, P. R. China. E-mail: huangx@
mail.hz.zj.cn
205

206
J. Cao and X. Huang
Scheme 1. Reagents and conditions: (a) 1, PhSeBr (1.2 eq)–ZnCl2 (0.3 eq), 30 min;
2, R1NH2 (2 eq), CH2Cl2, rt, 12 h; (b) R2NCO, K2CO3, DMF, 65ꢀC, 2 h; (c) 30%
H2O2, THF, rt, 30 min.
Organoselenium compounds have found a wide range of applications
in the areas of organic chemistry because of their utility as synthetic inter-
mediates.[5] Recently, it was reported that a-phenylseleno-b-amino esters
were synthesized by direct amino-phenylselenenylation of a,b-unsatu-
rated esters and phenylselenenyl halide with primary amines.[6] It is well
known that the phenylseleno group can be easily removed by oxidation–
elimination, giving access to carbon–carbon double bonds.[7] Therefore,
we planned to investigate the amino-phenylselenenylation reaction of
a,b-unsaturated esters to furnish a-phenylseleno-b-amino esters,[6]
followed by cyclization with isocynates to afford 5-phenylseleno-5,6-
dihydrouracils, and through further convenient oxidation–elimination
of the phenylseleno group, to afford 1,3-disubstituted uracils (Scheme 1).
This new strategy represents a general method for the synthesis of uracils
with different substituents at N-1 and N-3.
In the presence of 0.3 equiv. of zinc chloride, the reaction of 1.0 equiv.
of a,b-unsaturated esters, 1.2 equiv. of phenylselenenyl bromide, and 2.0
equiv. of primary amines was performed at room temperature. The
experimental results demonstrated that the amino-phenylselenenylation
of a,b-unsaturated ester could be undertaken smoothly to give a-phenyl-
seleno-b-amino esters 1 in good yields (Table 1).
Then a-phenylseleno-b-amino esters 1 were reacted with isocyanates
to afford the corresponding 5-phenylseleno-5,6-dihydrouracils 2. The
Table 1. Synthesis of a-phenylseleno-b-amino esters 1.
Entry
R1
1
Yield (%)a
1
2
3
4
Pr
Bu
Bn
Allyl
1a
1b
1c
1d
85
81
86
79
aIsolated yields based on a,b-unsaturated ester.

Synthesis of 1,3-Disubstituted Uracils
207
Table 2. Synthesis of 5-phenylseleno-5,6-dihydrouracils 2
Entry
R1
R2
2
Yield (%)a
1
2
3
4
5
6
7
8
9
Bn
Bu
Ph
2a
2b
2c
2d
2e
2f
90
84
86
80
77
87
85
83
75
Bn
Bn
Bn
Bn
Pr
Bu
Bu
Allyl
p-CH3C6H4
p-CH3OC6H4
m-ClC6H4
Bu
Bu
Ph
Bu
2g
2h
2i
aIsolated yields based on a-phenylseleno-b-amino esters 1.
screening of reaction conditions demonstrated that DMF as the solvent
and K2CO3 as the base at 65ꢀC were the most suitable for this reaction.
We then synthesized a series of 5-phenylseleno-5,6-dihydrouracils 2 to
study the scope of the reaction. When R1 was alkyl or allyl, or Bn and
R2 was alkyl or aryl, the reaction gave the products in good yields
(Table 2). Thus 5-phenylseleno-5,6-dihydrouracils 2 were easily prepared
in two steps and all of the products were characterized by spectroscopic
measurement.
5-Phenylseleno-5,6-dihydrouracils 2 were treated with 30% H2O2 to
afford 1, 3-disubstituted uracils 3. The yields were nearly quantitative
(Table 3). Thus uracils 3 were easily prepared in three steps and in high
yields from a,b-unsaturated ester, phenylselenenyl bromide, primary
amines, and isocyanates.
Table 3. Synthesis of uracils 3
Entry
R1
R2
3
Yield (%)a
1
2
3
4
5
6
7
8
9
Bn
Bu
Ph
3a
3b
3c
3d
3e
3f
97
95
97
94
98
96
98
96
93
Bn
Bn
Bn
Bn
Pr
Bu
Bu
Allyl
P-CH3C6H4
p-CH3OC6H4
m-ClC6H4
Bu
Bu
Ph
Bu
3g
3h
3i
aIsolated yields based on 5-phenylseleno-5,6-dihydrouracils 2.

208
J. Cao and X. Huang
In summary, we have developed a mild and efficient method for the
synthesis of 1,3-disubstituted uracils by amino-phenylselenenylation of
a,b-unsaturated ester and cyclization with isocyanates, followed by
oxidation–elimination of the phenylseleno group. The new strategy is a
general method for the synthesis of uracils with different substituents
at N-1 and N-3.
EXPERIMENTAL
General
Starting materials were obtained from commercial suppliers and used
without further purification. CH2Cl2 and DMF were distilled from CaH2
immediately prior to use. 1H NMR (400 MHz) and 13C NMR (100 MHz)
spectra were recorded on a Bruker Avance (400-MHz) spectrometer, using
CDCl3 as the solvent and TMS as internal standard. Mass spectra (EI,
70 eV) were recorded on an Agilent 5975 inert mass-selective dectector.
Infrared spectra were recorded on a Bruker Vector 22 spectrometer.
Elemental analyses were performed on a Flash EA1110 instrument.
HRMS were performed on a Waters Micromass GCT instrument.
General Procedure for the Synthesis of 3-Alkylamino-2-phenylseleno-
propanoate 1a–d
The a,b-unsaturated ester (1.0 mmol) was added to a solution containing
PhSeBr (1.2 mmol) and ZnCl2 (0.3 mmol) in CH2Cl2 (5 mL) at room
temperature. After 30 min, the amine R1NH2 (R1 ¼ Pr, Bu, Bn, allyl,
2.0 mmol) was added, and the reaction mixture was stirred for
about 12 h. The precipitate was then filtered. The filtrate was evaporated
to give the crude compound, which was chromatographed on silica gel
(hexane–EtOAc 4–9:1) to give the pure product.
Data for 1a–d
1
1a: Oil. H NMR (CDCl3) d 0.86 (t, 3H, J ¼ 7.2 Hz), 1.45 (m, 2H), 1.81
(broad, s, 1H), 2.56 (dd, 2H, J1 ¼ J2 ¼ 7.2 Hz), 2.95 (dd, 1H, Jl ¼ 12.8 Hz,
J2 ¼ 6.4 Hz), 3.07 (dd, 1H, J1 ¼ 12.8 Hz, J2 ¼ 8.4 Hz), 3.64 (s, 3H), 3.84
(dd, 1H, J1 ¼ 6.4 Hz, J2 ¼ 8.4 Hz), 7.20–7.40 (m, 3H), 7.50–7.65 (m,
2H). 13C NMR (CDCl3) d 172.5, 135.3, 128.8, 128.3, 127.3, 51.8, 51.0,
50.1, 43.2, 22.8, 11.4; MS m=z 301 (Mþ); IR nmax (cmꢁ1) 2955, 1729,
1437, 1255, 1130, 741.

Synthesis of 1,3-Disubstituted Uracils
209
1
1b: Oil. H NMR (CDCl3) d 0.87 (t, 3H, J ¼ 7.2 Hz), 1.29 (m, 2H),
1.39 (m, 2H), 2.00 (broad, s, 1H), 2.57 (dd, 2H, J1 ¼ J2 ¼ 7.2 Hz), 2.93
(dd, 1H, J1 ¼ 12.8 Hz, J2 ¼ 6.4 Hz), 3.06 (dd, 1H, J1 ¼ 12.8 Hz,
J2 ¼ 8.4 Hz), 3.63 (s, 3H), 3.81 (dd, 1H, J1 ¼ 6.4 Hz, J2 ¼ 8.4 Hz), 7.24–
7.32 (m, 3H), 7.55–7.59 (m, 2H); 13C NMR (CDCl3) d 172.7, 135.5,
129.0, 128.5, 127.4, 52.0, 50.3, 49.0, 43.3, 31.9, 20.2, 13.8; MS m=z 315
(Mþ); IR nmax (cmꢁ1) 2955, 1730, 1438, 1253, 1195, 1133, 740, 692.
1c: Oil. 1H NMR (CDCl3) d 2.05 (broad, s, 1H), 3.00 (dd, 1H,
J1 ¼ 12.6 Hz, J2 ¼ 6.4 Hz), 3.10 (dd, 1H, J1 ¼ 12.6 Hz, J2 ¼ 7.8 Hz), 3.66
(s, 3H), 3.80 (s, 2H), 3.84 (dd, 1H, J1 ¼ 6.4 Hz, J2 ¼ 7.8 Hz), 7.20–7.40
(m, 8H), 7.50–7.65 (m, 2H); 13C NMR (CDCl3) d 172.1, 139.5, 134.9,
128.5, 128.0, 127.9, 127.5, 127.2, 126.5, 52.8, 51.5, 49.3, 43.1; MS m=z
349 (Mþ); IR nmax (cmꢁ1) 2980, 1729, 1438, 1253, 1195, 1133, 734, 692.
1d: Oil. 1H NMR (CDCl3) d 2.12 (broad, s, 1H), 2.94 (dd, 1H,
J1 ¼ 12.8 Hz, J2 ¼ 6.4 Hz), 3.07 (dd, 1H, J1 ¼ 12.6 Hz, J2 ¼ 7.8 Hz), 3.23
(d, 2H, J ¼ 6.0), 3.64 (s, 3H), 3.80 (dd, 1H, J1 ¼ 6.4 Hz, J2 ¼ 7.8 Hz),
5.07 (dd, 1H, J1 ¼ 10.2 Hz, J2 ¼ 1.6 Hz), 5.14 (dd, 1H, J1 ¼ 17.2 Hz,
J2 ¼ 1.6 Hz), 5.78–5.87 (m, 1H), 7.25–7.33 (m, 3H), 7.57–7.60 (m, 2H);
13C NMR (CDCl3) d 172.6, 136.2, 135.5, 129.0, 128.5, 127.4, 116.2,
52.0, 51.7, 49.6, 43.2; MS m=z 299 (Mþ); IR nmax (cmꢁ1) 2949, 1729,
1438, 1255, 1196, 1140, 741, 692.
General Procedure for the Synthesis of 5-Phenylseleno-5,6-dihydrouracil
2a–i
The isocyanate (1.0 mmol) was added to a solution containing 3-alkyl-
amino-2-phenylseleno-propanoate 1 (1.0 mmol) and K2 CO3(0.5 mmol),
in DMF (5 mL), and the mixture was stirred at 65ꢀC. After 2 h, dilute
HCl solution (15 mL) and CH2Cl2 (15 mL) were added, and then the
CH2Cl2 layer was separated and washed with water (15 mL ꢂ 3). After
being dried over MgSO4, the solution was filtered and the solvent was
evaporated in vacuo. The residue was subjected to silica-gel column chro-
matography (hexane–EtOAc 3–6:1) to give pure product.
Data for 2a–i
1
2a: Oil. H NMR (CDCl3) d 0.94 (t, 3H, J ¼ 7.4 Hz), 1.35 (m, 2H), 1.54
(m, 2H), 3.29 (dd, 1H, J1 ¼ 13.5 Hz, J2 ¼ 3.6 Hz), 3.63 (dd, 1H,
J1 ¼ 13.5 Hz, J2 ¼ 4.0 Hz), 3.80 (m, 2H), 3.93 (dd, 1H, J1 ¼ 3.6 Hz,
J2 ¼ 4.0 Hz), 4.44 (d, 1H, J ¼ 14.8 Hz), 4.68 (d, 1H, J ¼ 14.8 Hz), 7.26–
7.36 (m, 8H), 7.51 (dd, 2H, J1 ¼ 8.0 Hz, J2 ¼ 1.0 Hz); 13C NMR (CDCl3)

210
J. Cao and X. Huang
d 168.4, 152.9, 135.9, 135.4, 129.2, 128.8, 128.6, 128.4, 127.8, 126.8, 51.7,
46.6, 41.1, 39.7, 30.2, 19.9, 13.7; MS m=z 416 (Mþ); IR nmax (cmꢁ1) 2957,
1708, 1668, 1475, 1438, 1199, 739, 696.
1
2b: White solid. Mp: 140–142ꢀC. H NMR (CDCl3) d 3.49 (dd, 1H,
J1 ¼ 13.6 Hz, J2 ¼ 3.2 Hz), 3.89 (dd, 1H, J1 ¼ 13.6 Hz, J2 ¼ 4.0 Hz), 4.08
(dd, 1H, J1 ¼ 3.2 Hz, J2 ¼ 4.0 Hz), 4.56 (d, 1H, J ¼ 14.8 Hz), 4.72 (d,
1H, J ¼ 14.8 Hz), 7.15 (d, 2H, J ¼ 7.6 Hz), 7.27–7.58 (m, 11H), 7.59 (d,
2H, J ¼ 7.6 Hz); 13C NMR (CDCl3) d 168.7, 153.0, 135.7, 135.6, 135.5,
129.4, 129.0, 128.8, 128.7, 128.5, 128.3, 128.1, 126.7, 52.0, 46.8, 40.0;
MS m=z 436 (Mþ); IR nmax (cmꢁ1) 3424, 1712, 1673, 1431, 1206, 696.
1
2c: White solid. Mp: 129–1318 C. H NMR (CDCl3) d 2.40 (s, 3H),
3.47 (dd, 1H, J1 ¼ 13.6 Hz, J2 ¼ 3.2 Hz), 3.89 (dd, 1H, J1 ¼ 13.6 Hz,
J2 ¼ 4.0 Hz), 4.07 (dd, 1H, J1 ¼ 3.2 Hz, J2 ¼ 4.0 Hz), 4.55 (d, 1H,
J ¼ 14.4 Hz), 4.71 (d, 1H, J ¼ 14.4 Hz), 7.02 (d, 2H, J ¼ 8.4 Hz), 7.25–
7.40 (m, 10H), 7.59 (d, 2H, J ¼ 8.4 Hz); 13C NMR (CDCl3) d 168.8,
153.1, 138.2, 136.8, 136.7, 132.8, 129.7, 129.3, 129.0, 128.8, 128.2,
128.1, 126.8, 52.0, 46.8, 40.0, 21.2; MS m=z 450 (Mþ); IR nmax (cmꢁ1
)
3030, 1715, 1677, 1472, 1429, 1369, 1203, 741.
2d: Low-melting-point solid. 1H NMR (CDCl3) d 3.44 (dd, 1H,
J1 ¼ 13.6 Hz, J2 ¼ 3.2 Hz), 3.80–3.87 (m, 4H), 4.05 (dd, 1H, J1 ¼ 3.2 Hz,
J2 ¼ 3.6 Hz), 4.53 (d, 1H, J ¼ 14.8 Hz), 4.68 (d, 1H, J ¼ 14.8 Hz), 6.95
(d, 2H, J ¼ 8.8 Hz), 7.04 (d, 2H, J ¼ 8.8 Hz), 7.25–7.38 (m, 8H), 7.56 (d,
2H, J ¼ 7.4 Hz); 13C NMR (CDCl3) d 168.9, 159.2, 153.1, 135.7, 135.6,
129.4, 129.3, 128.9, 128.7, 128.4, 128.0, 126.7, 114.3, 55.3, 51.9, 46.7,
39.8; MS m=z 466 (Mþ); IR nmax (cmꢁ1) 3028, 1714, 1675, 1472, 1425,
1369, 1201, 740.
2e: Low-melting-point solid. 1H NMR (CDCl3) d 3.50 (dd, 1H,
J1 ¼ 13.6 Hz, J2 ¼ 3.6 Hz), 3.90 (dd, 1H, J1 ¼ 13.6 Hz, J2 ¼ 3.8 Hz), 4.08
(dd, 1H, J1 ¼ 3.6 Hz, J2 ¼ 3.8 Hz), 4.56 (d, 1H, J ¼ 14.8 Hz), 4.72 (d,
1H, J ¼ 14.8 Hz), 7.02–7.09 (m, 2H), 7.27–7.43 (m, 10H), 7.58 (d, 2H,
J ¼ 7.6 Hz); 13C NMR (CDCl3) d 168.4, 152.5, 136.4, 135.8, 135.4,
134.4, 129.8, 129.4, 129.2, 129.0, 128.8, 128.7, 128.6, 128.1, 126.9,
126.4, 52.0, 46.8, 39.5; MS m=z 470 (Mþ), 472 (Mþ þ 2); IR nmax
(cmꢁ1) 2923, 1716, 1680, 1474, 1429, 1368, 1202, 745, 692.
2f: Oil. 1H NMR (CDCl3) d 0.88–0.95 (m, 6H), 1.29 (m, 2H), 1.48 (m,
2H), 1.58 (m, 2H), 3.29–3.40 (m, 3H), 3.72 (m, 2H), 3.79 (dd, 1H,
J1 ¼ 13.5 Hz, J2 ¼ 3.8 Hz), 3.97 (dd, 1H, J1 ¼ 3.6 Hz, J2 ¼ 3.8 Hz), 7.28–
7.34 (m, 3H), 7.62 (d, 2H, J ¼ 7.7 Hz); 13C NMR (CDCl3) d 168.5,
152.5, 135.3, 129.2, 128.7, 127.0, 50.1, 47.5, 40.8, 40.0, 30.1, 20.6, 19.9,
13.6, 11.1; MS m=z 368 (Mþ); IR nmax (cmꢁ1) 2959, 2931, 1708, 1669,
1475, 1437, 1388, 1199, 740, 691.
1
2g: Oil. H NMR (CDCl3) d 0.87–0.95 (m, 6H), 1.28–1.35 (m, 4H),
1.45–1.55 (m, 4H), 3.34–3.39 (m, 3H), 3.64 (m, 2H), 3.78 (dd, 1H,

Synthesis of 1,3-Disubstituted Uracils
211
J1 ¼ 11.6 Hz, J2 ¼ 2.4 Hz), 3.96 (dd, 1H, J1 ¼ 2.4 Hz, J2 ¼ 2.8 Hz), 7.29–
7.34 (m, 3H), 7.61 (d, 2H, J ¼ 6.8 Hz); 13C NMR (CDCl3) d 168.6,
152.6, 135.3, 129.2, 128.8, 127.0, 48.3, 47.6, 40.9, 40.1, 30.2, 29.4, 20.0,
19.9, 13.7, 13.6; MS m=z 382 (Mþ); IR nmax (cmꢁ1) 2927, 2867, 1709,
1671, 1474, 1386, 1198, 1109, 740, 692.
1
2h: Oil. H NMR (CDCl3) d 0.98 (t, 3H, J ¼ 7.3 Hz), 1.40 (m, 2H),
1.61 (m, 2H), 3.43 (m, 2H), 3.50 (dd, 1H, J1 ¼ 13.2 Hz, J2 ¼ 3.2 Hz),
4.00 (dd, 1H, J1 ¼ 13.2 Hz, J2 ¼ 3.6 Hz), 4.10 (dd, 1H, J1 ¼ 3.2 Hz,
J2 ¼ 3.6 Hz), 7.10 (d, 2H, J ¼ 7.4 Hz), 7.33–7.45 (m, 6H), 7.71 (d, 2H,
J ¼ 6.6 Hz); 13C NMR (CDCl3) d 169.0, 152.6, 135.7, 135.6, 129.5,
129.0, 128.9, 128.6, 128.2, 127.0, 48.4, 47.8, 40.3, 29.5, 20.0, 13.8; MS
m=z 402 (Mþ); IR nmax (cmꢁ1) 2928, 2866, 1717, 1680, 1471, 1429,
1369, 1200, 743, 693.
1
2i: Oil. H NMR (CDCl3) d 0.90 (t, 3H, J ¼ 7.3 Hz), 1.33 (m, 2H),
1.48 (m, 2H), 3.35 (dd, 1H, J1 ¼ 13.5 Hz, J2 ¼ 3.5 Hz), 3.65–3.75 (m,
3H), 3.95–4.01 (m, 3H), 5.18–5.25 (m, 2H), 5.75–5.80 (m, 1H) 7.25–
7.35 (m, 3H), 7.62 (d, 2H, J ¼ 6.7 Hz); 13C NMR (CDCl3) d 168.6,
152.6, 135.6, 132.2, 129.3, 128.9, 127.0, 118.9, 50.8, 46.8, 41.1, 40.0,
30.2, 20.0, 13.8; MS m=z 366 (Mþ); IR nmax (cmꢁ1) 2958, 2866, 1709,
1670, 1474, 1438, 1199, 740, 692.
General Procedure for the Synthesis of Uracils 3a–i
(H2O2 30%, 0.5 mL) was added to a solution containing 5-phenylseleno-
5,6-dihydrouracils 2 (1.0 mmol) in THF (5 mL), and the mixture was
stirred at room temperature. After 30 min, water (15 mL) and CH2Cl2
(15 mL) were added, and then the CH2Cl2 layer was separated. After
being dried over MgSO4, the solution was filtered, and the solvent was
evaporated in vacuo. The residue was subjected to silica-gel column chro-
matography (hexane–EtOAc 3–6:1) to give pure product.
Data for 3a–i
1
3a: Oil. H NMR (CDCl3) d 0.94 (t, 3H, J ¼ 7.3 Hz), 1.36 (m, 2H), 1.61
(m, 2H), 3.95 (t, 2H, J ¼ 7.5 Hz), 4.92 (s, 2H), 5.71 (d, 1H, J ¼ 7.9 Hz),
7.14 (d, 1H, J ¼ 7.9 Hz), 7.27–7.39 (m, 5H); 13C NMR (CDCl3) d
162.7, 151.5, 141.5, 135.2, 128.9, 128.2, 127.8, 101.9, 52.0, 41.0, 29.4,
20.0, 13.6; MS m=z 258 (Mþ); IR nmax (cmꢁ1) 2968, 1714, 1659, 1456,
1352, 1237, 805. HRMS calcd. for C15H18N2O2: 258.1368. Found:
258.1372.
1
3b: White solid. Mp: 153–1558ꢀC. H NMR (CDCl3) d 4.95 (s, 2H),
5.85 (d, 1H, J ¼ 7.9 Hz), 7.23–7.27 (m, 3H), 7.33–7.51 (m, 8H); 13C NMR

212
J. Cao and X. Huang
(CDCl3) d 162.9, 151.8, 142.3, 135.1, 135.0, 129.4, 129.1, 128.8, 128.6,
128.3, 128.2, 102.5, 52.4; MS m=z 278 (Mþ); IR nmax (cmꢁ1) 2924,
1713, 1662, 1444, 1225, 697. Anal. calcd. for C17H14N2O2: C, 73.37%;
H, 5.07%; N, 10.07%. Found: C, 73.38%; H, 5.08%; N, 10.10%.
1
3c: White solid. Mp: 156–1588ꢀC. H NMR (CDCl3) d 2.41 (s, 3H),
4.88 (s, 2H), 5.79 (d, 1H, J ¼ 7.9 Hz), 7.14 (d, 2H, J ¼ 8.2 Hz), 7.25 (d, 1H,
J ¼ 7.9 Hz), 7.29–7.39 (m, 7H); 13C NMR (CDCl3) d 162.9, 151.5, 142.5,
138.3, 135.1, 132.2, 129.7, 128.7, 128.1, 127.9, 127.6, 101.9, 52.0, 20.9; MS
m=z 292 (Mþ); IR nmax (cmꢁ1) 3069, 1716, 1661, 1449, 1387, 1347, 1221,
820. Anal. calcd. for C18H16N2O2: C, 73.95%; H, 5.52%; N, 9.58%.
Found: C, 73.97%; H, 5.51%; N, 9.59%.
1
3d: White solid. Mp: 158–1608ꢀC. H NMR (CDCl3) d 3.82 (s, 3H),
4.92 (s, 2H), 5.82 (d, 1H, J ¼ 8.0 Hz), 6.99 (d, 2H, J ¼ 9.0 Hz), 7.15 (d, 2H,
J ¼ 9.0 Hz), 7.23 (d, 1H, J ¼ 8.0 Hz), 7.32–7.39 (m, 5H); 13C NMR
(CDCl3) d 163.1, 159.4, 151.9, 142.3, 135.1, 129.1, 129.0, 128.5, 128.2,
127.5, 114.6, 102.3, 55.3, 52.3; MS m=z 308 (Mþ); IR nmax (cmꢁ1
)
1710, 1662, 1511, 1444, 1250, 1028. Anal. calcd. for C18H16N2O3: C,
70.12%; H, 5.23%; N, 9.09%. Found: C, 70.12%; H, 5.23%; N, 9.12%.
1
3e: White solid. Mp: 120–1228ꢀC. H NMR (CDCl3) d 4.89 (s, 2H),
5.79 (d, 1H, J ¼ 8.0 Hz), 7.15 (m, 1H), 7.26 (m, 2H), 7.30–7.42 (m, 7H);
13C NMR (CDCl3) d 162.6, 151.5, 142.9, 136.2, 135.1, 134.7, 130.3,
129.1, 129.0, 128.8, 128.6, 128.3, 126.8, 102.3, 52.4; MS m=z 312 (Mþ),
314 (Mþ þ 2); IR nmax (cmꢁ1) 1716, 1664, 1445, 1386, 1350, 1220, 699,
687. Anal. calcd. for C17H13ClN2O2: C, 65.29%; H, 4.19%; N, 8.96%.
Found: C, 65.29%; H, 4.27%; N, 8.99%.
3f: Oil. 1H NMR (CDCl3) d 0.89–0.95 (m, 6H), 1.33 (m, 2H), 1.57 (m,
2H), 1.69 (m, 2H), 3.67 (t, 2H, J ¼ 7.2 Hz), 3.90 (t, 2H, J ¼ 7.5 Hz), 5.68
(d, 1H, J ¼ 7.9 Hz), 7.08 (d, 1H, J ¼ 7.8 Hz); 13C NMR (CDCl3) d 163.1,
151.3, 142.1, 101.4, 51.3, 41.0, 30.0, 22.2, 20.1, 13.7, 10.8; MS m=z 210
(Mþ); IR nmax (cmꢁ1) 2961, 1706, 1659, 1456, 1352, 1237, 805. HRMS
calcd. for C11H18N2O2: 210.1368. Found: 210.1361.
3g:[8] Oil. 1H NMR (CDCl3) d 0.92–0.98 (m, 6H), 1.33–1.40 (m, 4H),
1.58–1.67 (m, 4H), 3.73 (t, 2H, J ¼ 7.4 Hz), 3.93 (t, 2H, J ¼ 7.6 Hz), 5.70
(d, 1H, J ¼ 7.8 Hz), 7.09 (d, 1H, J ¼ 7.8 Hz); 13C NMR (CDCl3) d 163.1,
151.4, 142.0, 101.5, 49.5, 41.0, 31.0, 30.0, 20.1, 19.7, 13.7, 13.6; MS m=z
224 (Mþ); IR nmax (cmꢁ1) 2959, 2869, 1707, 1653, 1457, 1352, 1222, 806.
1
3h: White solid. Mp: 98–1008ꢀC. H NMR (CDCl3) d 0.97 (t, 3H,
J ¼ 3.2 Hz), 1.37 (m, 2H), 1.69 (m, 2H), 3.74 (t, 2H, J ¼ 7.3 Hz), 5.82 (d,
1H, J ¼ 7.9 Hz), 7.18–7.23 (m, 3H), 7.42 (d, 1H, J ¼ 7.3 Hz), 7.47–7.51
(m, 2H); 13C NMR (CDCl3) d 163.1, 151.4, 143.0, 135.0, 129.3, 128.6,
128.1, 101.8, 50.0, 31.0, 19.6, 13.5; MS m=z 244 (Mþ); IR nmax (cmꢁ1
)
2960, 1711, 1659, 1445, 1114, 697. Anal. calcd. for C14H16N2O2: C,
68.83%; H, 6.60%; N, 11.47%. Found: C, 68.75%; H, 6.63%; N, 11.48%.

Synthesis of 1,3-Disubstituted Uracils
213
1
3i: Oil. H NMR (CDCl3) d 0.94 (t, 3H, J ¼ 7.2 Hz), 1.37 (m, 2H),
1.61 (m, 2H), 3.94 (t, 2H, J ¼ 8.0 Hz), 4.36 (d, 2H, J ¼ 5.6 Hz), 5.23–
5.33 (m, 2H), 5.74 (d, 1H, J ¼ 7.6 Hz), 5.88 (m, 1H) 7.09 (d, 1H,
J ¼ 7.6 Hz); 13C NMR (CDCl3) d 163.0, 151.4, 141.4, 131.7, 119.2,
102.0, 51.0, 41.1, 29.6, 20.2, 13.8; MS m=z 208 (Mþ); IR nmax (cmꢁ1
)
2927, 2858, 1707, 1662, 1455, 1231, 806. HRMS calcd. for
C11H16N2O2: 208.1212. Found: 208.1205.
ACKNOWLEDGMENTS
We are grateful to the Natural Science Foundation of China (Project No.
20672095) and the CAS Academician Foundation of Zhejiang Province.
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