Hypervalent iodine in synthesis: Part 86. Selective copper-catalyzed N-monoarylation and N1,N3-diarylation of uracil and its derivatives with diaiyliodonium salts

Article abstract of DOI:10.1002/hlca.200590010

N-Arylation of uracil and its derivatives 2 with diaryliodonium salts 1 was investigated in order to explore a new synthetic methodology associated with N-aryluracil derivatives. In the presence of K₂CO₃, the copper-catalyzed arylation gave N¹,N³-diarylation products with high selectivity and in good yields (Table 2). However, the use of NaOAc as the base in the copper-catalyzed arylation of 6-methyluracil (2a) resulted in N₃-arylation products with high selectivity, and, in the copper-catalyzed arylation of uracil (2b) or 5-methyluracil (=thymine; 2c), N¹-arylation products were the major products (Table 3).

Full text of DOI:10.1002/hlca.200590010

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Helvetica Chimica Acta ± Vol. 88 (2005)
Hypervalent Iodine in Synthesis
Part 86
Selective Copper-Catalyzed N-Monoarylation and N1,N3-Diarylation of Uracil and Its
Derivatives with Diaryliodonium Salts
by Tao Zhou*a)1), Ti-Cong Lib), and Zhen-Chu Chenb)
a) Faculty of Life Science and Biotechnology, Ningbo University, Zhejiang, 315211, P. R. China
b) Department of Chemistry, Zhejiang University (Xixi Campus), Hangzhou, 310028, P. R. China
N-Arylation of uracil and its derivatives 2 with diaryliodonium salts 1 was investigated in order to explore a
new synthetic methodology associated with N-aryluracil derivatives. In the presence of K2CO3, the copper-
catalyzed arylation gave N1,N3-diarylation products with high selectivity and in good yields (Table 2). However,
the use of NaOAc as the base in the copper-catalyzed arylation of 6-methyluracil (2a) resulted in N3-arylation
products with high selectivity, and, in the copper-catalyzed arylation of uracil (2b) or 5-methyluracil (ˆthymine;
2c), N1-arylation products were the major products (Table 3).
Introduction. ± Many N-substituted uracil derivatives possess biological activity [1].
They are also useful as biochemical diagnostic probes [2] and as potential synthons [3].
Several methods for the synthesis of these compounds are known, e.g., N1,N3-
diaryluracils have been prepared by base-catalyzed condensation of enamines with aryl
isocyanates [4]; N1,N3-diaryl-methyluracils have been obtained by treating 1,3-diaryl-
ureas with diketene [5]; N1-aryluracils have been synthesized from substituted
ureidopropanoic acids or 1-acrylyl-3-arylureas [6]; N1-aryl-6-methyluracils have been
obtained from the reaction of 6-methyl-1,3-oxazine-2,4(3H)-dione with arylamines
[7]; N3-aryluracils have been synthesized via cycloreversion of norbornene-fused
pyrimidinediones [8]; N3-aryl-6-methyluracils have been prepared by the cyclization of
ureidobutenoate [9]. However, methods involving the direct N-arylation of uracil have
rarely been reported [10].
As part of our research interest in the synthetic applications of transition-metal-
catalyzed arylation reactions with diaryliodonium salts [11], the copper-catalyzed
arylation of uracil and its derivatives with diaryliodonium salts was investigated to
achieve N1,N3-diarylation or N-monoarylation with high selectivity.
Results and Discussion. ± To find the optimum arylation conditions, the effects of
bases and solvents on N-phenylation of 6-methyluracil (2a) with diphenyliodonium
tetrafluoroborate (1a) were examined, which yielded 6-methyl-1,3-diphenyluracil (3a)
and 6-methyl-3-phenyluracil (4a) (see Table 1). The results showed that DMF was the
1
)
Present address: Department of Pharmacy, Kingꢁs College London, Franklin-Wilkins Building, 150
Stamford Street, London SE1 9NN, UK (tel: (‡44)2078484844; fax: (‡44)2078484800; e-mail:
tao.zhou@kcl.ac.uk).
ꢀ 2005 Verlag Helvetica Chimica Acta AG, Zürich

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291
Table 1. Effect of Base andSolvent on N-Phenylation of 6-Methyluracil (2a). Conditions: all reactions were run
with diphenyliodonium tetrafluoroborate (1a; 1 mmol), 2a (1 mmol), CuI (10 mol-%), base (2 mmol), and
solvent (5 ml) under N2 at 408 for 6 h.
Base
Solvent
Yielda) of 3a [%]
Yielda) of 4a [%]
K2CO3
Na2CO3
NaHCO3
K3PO4
NaOAc
K2HPO4
K2CO3
K2CO3
K2CO3
K2CO3
DMF
DMF
DMF
DMF
DMF
DMF
DMF/H2O 4.5 : 0.5
DMF/H2O 4.75 : 0.25
CHCl3
59
30
8
trace
trace
±
5
7
7
29
5
21
37
40
59
trace
32
50
12
4
CH2Cl2
a) Isolated yield based on 1a
best choice of solvent, K2CO3 the most-suitable base for N1,N3-diarylation, and NaOAc
the most-suitable base for N3-arylation.
To establish the universality of the reaction, first the N1,N3-diarylation of uracil (2b)
was investigated. In the presence of K2CO3 and CuI, the reaction of diaryliodonium
salts 1 with uracil was complete after 3 ± 4 h at 408 in DMF, to give N1,N3-diarylation
products 3 in good yield and high selectivity (see Table 2). The reaction of diaryl-
iodonium salts 1 with uracil derivatives such as 6-methyluracil (2a) or thymine (2c)
under the same reaction conditions was straightforward, as predictable products were
obtained (see Table 2).
The reaction of 6-methyluracil (2a) with diaryliodonium salts 1 for 10 h at 408 in
DMF was examined in the presence of NaOAc as the base instead of K2CO3. N3-
Arylation products were formed with high selectivity, besides a small amount of N1,N3-
diarylation products; but no N1-arylation took place (see Table 3, Entries 1 ± 5). The
reactions of uracil (2b) and thymine (2c) with diaryliodonium salts 1 in the presence of
NaOAc yielded N1-arylation products as the major product (Entries 6 ± 13), besides a
small amount of N1,N3-diarylation product and, in some cases, the N3-arylation product
(Entries 12 and 13).
Although the different results of the N-arylation of 6-methyluracil (2a) compared
with that of both uracil (2b) and thymine (2c) in the presence of a weak base such as
NaOAc can be explained by steric hindrance at the N1-position of 2a due to MeÀC(6),
the regioselectivity of N-arylation is also influenced by the fact that HÀN(1) of both 2b
and 2c being more acidic than HÀN(3).
The position of monoarylation of 2 was determined by the Shugar ± Fox method
[12], which is based on the induced bathochromic shift in the UV spectrum of the

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Table 2. N1,N3-Diarylation of Uracil (2b), 6-Methyluracil (2a), or Thymine (2c). Conditions: all reactions were
run with 1 (1.2 mmol), 2 (0.5 mmol), CuI (10 mol-%), K2CO3 (2 mmol), and DMF (5 ml) under N2 at 408 for
3 ± 4 h.
Ar
R
Product
Yielda) [%]
Ph
6-Me
6-Me
6-Me
6-Me
H
H
H
5-Me
5-Me
5-Me
3a
3b
3c
3d
3e
3f
3g
3h
3i
83
65
69
55
68
62
72
72
85
52
4-MeC6H4
4-ClC6H4
4-BrC6H4
Ph
4-MeC6H4
4-ClC6H4
Ph
4-MeC6H4
4-BrC6H4
3j
a) Isolated yield based on uracil.
product on changing from neutral to alkaline pH. This shift is 20 ± 30 nm in the case of
the 3-substituted product of uracil and its derivatives and is missing in the case of the 1-
substituted product of uracil and its derivatives. The position of monoarylation of 2 can
also be determined by MS analysis of the 1- or 3-substituted products of uracil [13]. For
example, the fragmentions of N1-(4-methylphenyl)thymine (5g) were different from
those of N3-(4-methylphenyl)thymine (5g') (see Scheme).
Conclusions. ± The copper-catalyzed N-arylation of uracil or its derivatives with
diaryliodonium salts proceeds under mild reaction conditions. With the aid of a suitable
base, a convenient method for the synthesis of N1,N3-diaryluracil, N3-aryl-6-methylur-
acil, N1-aryluracil, and N1-arylthymine has been developed.
Experimental Part
General. M.p.: uncorrected. UV Spectra: Hitachi-U-3400 spectrometer; lmax (log e) in nm. IR Spectra:
Vector-22-IR spectrometer; KBr pellets; n in cmÀ1. 1H-NMR: Avance-400 spectrometer; CDCl3 or (D6)DMSO
solns. with SiMe4 as internal standard; d in ppm, J in Hz. MS: HP5859B mass spectrometer; in m/z (rel. %).
Elemental analyses: EA1110.
N1,N3-Diaryluracils: General Procedure. A mixture of diaryliodonium salt 1 (1.2 mmol), uracil or its
derivatives 2 (0.5 mmol), K2CO3 (2 mmol), CuI (10 mol-%), and DMF (5 ml) was stirred under N2 at 408 for 3 ±
4 h. The mixture was diluted with sat. aq. NH4Cl soln. (20 ml) and extracted with AcOEt (3 Â 15 ml), the
combined org. phase washed with brine, dried (Na2SO4), and evaporated, and the residue purified by prep. TLC
(silica gel, cyclohexane/AcOEt 1:2): pure 3.
6-Methyl-1,3-diphenylpyrimidine-2,4(1H,3H)-dione (3a): M.p. 182 ± 1838 ([5]: no m.p. reported). UV
(EtOH): 266 (4.11). IR: 1712, 1662, 1594, 1489, 1408, 1368, 1235, 823, 764. 1H-NMR (CDCl3): 1.94 (s, 3 H); 5.86
‡
(s, HÀC(5)); 7.26 ± 7.31 (m, 4 H); 7.38 ± 7.41 (m, 1 H); 7.45 ± 7.52 (m, 5 H). MS: 278 (57.02, M ), 159 (100), 144
(34.80), 131 (48.31), 130 (51.50), 118 (32.61).

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Table 3. N3-Arylation of 6-Methyluracil (2a) and N1-Arylation of Uracil (2b) or Thymine (2c). Conditions: all
reactions were run with 1 (1.0 mmol), 2 (1.2 mmol), CuI (10 mol-%), NaOAc (2 mmol), and DMF (5 ml)
under N2 at 408 for 10 h.
Entry
1
Ar
2
Product
Yielda) [%]
1
2
3
4
5
6
7
8
9
10
11
12b)
13c)
1a
1b
1c
1d
1e
1a
1b
1c
1d
1e
1a
1b
1d
Ph
2a
2a
2a
2a
2a
2b
2b
2b
2b
2b
2c
2c
2c
4a
4b
4c
4d
4e
5a
5b
5c
5d
5e
5f
5g
5h
60
46
42
43
40
53
50
54
41
45
41
46
43
4-MeC6H4
4-ClC6H4
4-BrC6H4
MeOC6H4
Ph
4-MeC6H4
4-ClC6H4
4-BrC6H4
4-MeOC6H4
Ph
4-MeC6H4
4-BrC6H4
b
c
a) Isolated yield based on iodonium salt. ) N3-(4-Methylphenyl)thymine (5g') was obtained in 7% yield. ) N3-
(4-Bromophenyl)thymine (5h') was obtained in 6% yield.
6-Methyl-1,3-bis(4-methylphenyl)pyrimidine-2,4(1H,3H)-dione (3b): M.p. 153 ± 1548. UV (EtOH): 266
1
(4.09). IR: 1711, 1670, 1513, 1408, 1376, 818, 764. H-NMR (CDCl3): 1.93 (s, 3 H); 2.32 (s, 3 H); 2.40 (s, 3 H);
‡
5.84 (s, HÀC(5)); 7.14 ± 7.17 (m, 4 H); 7.25 ± 7.30 (m, 4 H). MS: 306 (41.46, M ), 173 (100), 158 (25.72), 145
(37.71), 144 (37.56), 132 (32.49). Anal. calc. for C19H18N2O2: C 74.49, H 5.92, N 9.14; found: C 74.30, H 6.02, N
9.04.
1,3-Bis(4-chlorophenyl)-6-methylpyrimidine-2,4(1H,3H)-dione (3c): M.p. 137 ± 1398. UV (EtOH): 264
(4.17). IR: 1717, 1675, 1491, 1415, 1375, 1088, 1016, 805. 1H-NMR (CDCl3): 1.95 (s, 3 H); 5.86 (s, HÀC(5)); 7.21
‡
(d, J ˆ 8.6, 2 H); 7.24 (d, J ˆ 8.6, 2 H); 7.44 (d, J ˆ 8.40, 2 H); 7.49 (d, J ˆ 8.4, 2 H). MS: 348 (15.04, [M ‡ 2] ),
‡
346 (23.25, M ), 195 (33.29), 193 (100), 178 (25.50), 165 (20.40), 164 (24.11), 152 (25.78), 111 (23.10). Anal.
calc. for C17H12Cl2N2O2: C 58.79, H 3.48, N 8.06; found: C 58.65, H 3.46, N 8.17.
1,3-Bis(4-bromophenyl)-6-methylpyrimidine-2,4(1H,3H)-dione (3d): M.p. 191 ± 1938. UV (EtOH): 265
(4.15). IR: 1715, 1671, 1489, 1412, 1368, 1070, 1013, 818, 798, 761. 1H-NMR (CDCl3): 1.94 (s, 3 H); 5.86
‡
‡
(s, HÀC(5)); 7.14 ± 7.18 (m, 4 H); 7.58 ± 7.66 (m, 4 H). MS: (15.91, [M ‡ 4] ), 436 (30.42, [M ‡ 2] ), 434 (16.14,
‡
M ), 239 (96.95), 237(100), 224 (21.42), 222 (22.69), 197 (17.01), 196 (29.01), 130 (61.52). Anal. calc. for
C17H12Br2N2O2: C 46.80, H 2.77, N 6.42; found: C 46.63, H 2.79, N 6.29.

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Scheme. MS Fragmentation of N1-(4-Methylphenyl)thymine (5g) and N3-(4-Methylphenyl)thymine (5g')
1,3-Diphenylpyrimidine-2,4(1H,3H)-dione (3e): M.p. 206 ± 2078 ([10a]: 207 ± 2108). UV (EtOH): 271
(3.97). IR: 1717, 1682, 1594, 1490, 1429, 1379, 1303, 1182, 1075, 815, 763, 701. 1H-NMR (CDCl3): 5.99 (d, J ˆ 8.0,
1 H); 7.29 (m, 2 H); 7.39 ± 7.44 (m, 5 H); 7.47 ± 7.52 (m, 4 H).
1,3-Bis(4-methylphenyl)pyrimidine-2,4(1H,3H)-dione (3f): M.p. 176 ± 1778. UV (EtOH): 271 (3.95). IR:
1
1719, 1676, 1511, 1430, 1375, 1318, 1300, 1278, 822, 799, 761. H-NMR (CDCl3): 2.39 (s, 6 H); 5.96 (d, J ˆ 8.0,
‡
HÀC(5)); 7.16 (d, J ˆ 8.2, 4 H); 7.29 (d, J ˆ 8.2, 4 H); 7.38 (d, J ˆ 8.0, HÀC(6)). MS: 292 (45.69, M ), 159 (100),
131 (28.34), 130 (66.46), 118 (17.15), 91 (54.69). Anal. calc. for C18H16N2O2: C 73.96, H 5.52, N 9.58; found: C
73.77, H 5.48, N 9.47.
1,3-Bis(4-chlorophenyl)pyrimidine-2,4(1 H,3 H)-dione (3g): M.p. 148 ± 1498. UV (EtOH): 268 (4.02). IR:
1721, 1675, 1493, 1434, 1405, 1367, 1291, 1092, 1018, 827, 797. 1H-NMR (CDCl3): 6.00 (d, J ˆ 8.0, HÀC(5)); 7.22
‡
‡
(d, J ˆ 8.0, 1 H); 7.33 ± 7.39 (m, 4 H); 7.47 (m, 4 H). MS: 334 (21.48, [M ‡ 2] ), 332 (32.87, M ), 181 (32.93), 179
(100), 153 (18.36), 151 (40.65), 138 (15.36), 111 (20.34). Anal. calc. for C16H10Cl2N2O2: C 57.66, H 3.00, N 8.40;
found: C 57.50, H 2.95, N 8.25.

Helvetica Chimica Acta ± Vol. 88 (2005)
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5-Methyl-1,3-diphenylpyrimidine-2,4(1H,3H)-dione (3h): M.p. 184 ± 1858 ([4]: no m.p. reported). UV
(EtOH): 275 (4.04). IR: 1707, 1663, 1597, 1491, 1430, 1374, 1318, 1304, 762, 694. 1H-NMR (CDCl3): 2.03 (s, 3 H);
7.26 (m, 1 H); 7.29 (m, 2 H); 7.40 (m, 4 H); 7.45 ± 7.49 (m, 4 H).
5-Methyl-1,3-bis(4-methylphenyl)pyrimidine-2,4(1H,3H)-dione (3i): M.p. 164 ± 1658. UV (EtOH) 276
(4.02). IR: 1714, 1669, 1512, 1422, 1364, 1302, 1201, 1169, 1141, 1111, 816, 764, 745. 1H-NMR (CDCl3): 2.01
‡
(s, 3 H); 2.39 (s, 6 H); 7.14 (d, J ˆ 8.3, 4 H); 7.22 ± 7.24 (m, 1 H); 7.28 (d, J ˆ 8.3, 4 H). MS: 306 (61.45, M ), 173
(100), 145 (26.88), 144 (79.47), 130 (35.39), 118 (11.92), 91 (37.17). Anal. calc. for C19H18N2O2: C 74.49, H 5.92,
N 9.14; found: C 74.34, H 5.99, N 9.11.
1,3-Bis(4-bromophenyl)-5-methylpyrimidine-2,4(1H,3H)-dione (3j): M.p. 191 ± 1928. UV (EtOH): 274
(4.08). IR: 1715, 1669, 1489, 1428, 1400, 1369, 1309, 1071, 1013, 890, 817, 763. 1H-NMR (CDCl3): 2.02 (s, 3 H);
‡
‡
7.15 (m, 2 H); 7.23 (s, 1 H); 7.28 (m, 2 H); 7.61 (m, 4 H). MS: 438 (18.24, [M ‡ 4] ), 436 (36.05, [M ‡ 2] ), 434
‡
(19.00, M ), 239 (58.06), 237 (60.23), 211 (12.47), 210 (29.63), 209 (14.11), 208 (27.85), 158 (48.03), 130 (100).
Anal. calc. for C17H12Br2N2O2: C 46.80, H 2.77, N 6.42; found: C 46.68, H 2.73, N 6.53.
N3-Aryl-6-methyluracils, N1-Aryluracils, and N1-Arylthymines: General Procedure. A mixture of diaryl-
iodonium salt 1 (1 mmol), uracil or its derivatives 2 (1.2 mmol), NaOAc (2 mmol), CuI (10 mol-%), and DMF
(5 ml) was stirred under N2 at 408 for 10 h. The mixture was diluted with sat. aq. NH4Cl soln. (20 ml) and
extracted with AcOEt (3 Â 15 ml), the combined org. phase washed with brine, dried (Na2SO4), and
evaporated, and the residue purified by prep. TLC (cyclohexane/AcOEt 1:2): 4 or 5.
6-Methyl-3-phenylpyrimidine-2,4(1H,3H)-dione (4a): M.p. 243 ± 2458. ([12]: 224 ± 2508). UV (EtOH): 261
(4.02). UV (pH 13): 285 (4.08). IR: 3223, 3185, 3114, 1711, 1657, 1506, 1488, 1457, 1418, 1353, 1209, 1121, 823,
774, 703. 1H-NMR (CDCl3): 2.06 (s, 3 H); 5.66 (s, HÀC(5)); 7.23 (m, 2 H); 7.43 ± 7.51 (m, 3 H); 9.41 (br., NH).
6-Methyl-3-(4-methylphenyl)pyrimidine-2,4(1H,3H)-dione (4b): M.p. 2648 (dec.) ([9]: no m.p. reported).
UV (EtOH): 261 (3.99). UV (pH 13): 285 (4.04). IR: 3173, 1738, 1648, 1520, 1411, 1354, 1212, 1122, 821, 766,
718. 1H-NMR (CDCl3): 2.12 (s, 3 H); 2.39 (s, 3 H); 5.66 (s, HÀC(5)); 7.10 (d, J ˆ 8.2, 2 H); 7.29 (d, J ˆ 8.2, 2 H);
‡
8.88 (br., NH). MS: 216 (53.61, M ), 133 (100), 132 (19.82), 105 (18.92), 104 (23.68), 84 (27.57).
3-(4-Chlorophenyl)-6-methylpyrimidine-2,4(1H,3H)-dione (4c): M.p. 2828 (dec.) ([13]: 3428 (dec.)). UV
(EtOH): 261 (4.05). UV (pH 13): 285 (4.11). IR: 3230, 3179, 3096, 1738, 1647, 1584, 1497, 1418, 1352, 1214, 1124,
1
1093, 1020, 831, 765, 717. H-NMR (CDCl3): 2.16 (s, 3 H); 5.67 (s, HÀC(5)); 7.17 (d, J ˆ 8.8, 2 H); 7.46 (d, J ˆ
‡
‡
8.8, 2 H); 8.61 (br., NH). MS: 238 (25.11, [M ‡ 2] ), 236 (74.35, M ), 153 (100), 125 (27.44), 83 (62.33).
3-(4-Bromophenyl)-6-methylpyrimidine-2,4(1H,3H)-dione (4d): M.p. 3208 (dec.). UV (EtOH): 261 (4.03).
UV (pH 13): 285 (4.08). IR: 3225, 3176, 3092, 1736, 1647, 1491, 1414, 1353, 1123, 1071, 1016, 823, 765, 714.
1H-NMR ((D6)DMSO): 2.09 (s, 3 H); 5.57 (s, HÀC(5)); 7.19 (d, J ˆ 8.8, 2 H); 7.64 (d, J ˆ 8.8, 2 H); 11.30 (br.,
‡
‡
NH). MS: 282 (74.27, [M ‡ 2] ), 280 (75.03, M ), 199 (84.86), 197 (84.93), 90 (100), 83 (72.32), 68 (91.67), 63
(73.54), 55 (41.32). Anal. calc. for C11H9BrN2O2: C 46.98, H 3.23, N 9.96; found: C 46.79, H 3.16, N 9.85.
3-(4-Methoxyphenyl)-6-methylpyrimidine-2,4(1H,3H)-dione (4e): M.p. 249 ± 2518. UV (EtOH): 263 (4.04).
UV (pH 13): 283 (4.09). IR: 3236, 3180, 3087, 1734, 1653, 1520, 1413, 1304, 1261, 1176, 1035, 767, 647. 1H-NMR
((D6)DMSO): 2.08 (s, 3 H); 3.78 (s, 3 H); 5.53 (s, HÀC(5)); 6.97 (d, J ˆ 8.8, 2 H); 7.08 (d, J ˆ 8.8, 2 H); 9.28
‡
(br., NH). MS: 232 (30.22, M ), 149 (100), 134 (39.43), 106 (22.34). Anal. calc. for C12H12N2O3: C 62.06, H 5.21,
N 12.06; found: C 61.87, H 5.11, N 12.23.
1-Phenylpyrimidine-2,4(1H,3H)-dione (5a): M.p. 242 ± 2448 ([14]: 2468). UV (EtOH): 268 (4.05). UV (pH
13): 268 (3.94). IR: 3161, 3098, 3053, 1744, 1693, 1628, 1601, 1500, 1441, 1423, 1384, 1299, 1283, 1258, 825, 758,
688. 1H-NMR ((D6)DMSO): 5.67 (dd, J ˆ 8.0, 2.0, HÀC(5)); 7.41 ± 7.45 (m, 3 H); 7.50 (m, 2 H); 7.71 (d, J ˆ 8.0,
1 H), 11.44 (br., NH).
1-(4-Methylphenyl)pyrimidine-2,4(1H,3H)-dione (5b): M.p. 225 ± 2278 ([15]: 226.5 ± 2288). UV (EtOH):
268 (4.03). UV (pH 13): 267 (3.93). IR: 3158, 3100, 3135, 1742, 1691, 1516, 1448, 1384, 1297, 1260, 825, 813, 725,
1
712. H-NMR ((D6)DMSO): 2.35 (s, 3 H); 5.65 (dd, J ˆ 8.0, 2.0, HÀC(5)); 7.29 (s, 4 H); 7.66 (d, J ˆ 8.0, 1 H);
11.41 (br., NH).
1-(4-Chlorophenyl)pyrimidine-2,4(1H,3H)-dione (5c): M.p. 253 ± 2558 ([6]: 2588). UV (EtOH): 263 (4.18).
1
UV (pH 13): 263 (4.08). IR: 3088, 1718, 1664, 1539, 1450, 1382, 1291, 1274, 1090, 981, 820, 760, 714. H-NMR
((D6)DMSO): 5.68 (d, J ˆ 7.6, HÀC(5)); 7.47 (m, 2 H); 7.58 (m, 2 H); 7.71 (d, J ˆ 7.6, HÀC(6)); 11.45
(br., NH).
1-(4-Bromophenyl)pyrimidine-2,4(1H,3H)-dione (5d): M.p. 272 ± 2748 ([16]: 275 ± 2768). UV (EtOH): 264
(4.12). UV (pH 13): 265 (4.01). IR: 3107, 3022, 1718, 1660, 1495, 1472, 1383, 1291, 1077, 979, 819, 746, 712.
1H-NMR ((D6)DMSO): 5.68 (dd, J ˆ 8.0, 2.4, HÀC(5)); 7.40 (m, 2 H); 7.67 ± 7.72 (m, 3 H); 11.47 (br., NH).
1-(4-Methoxyphenyl)pyrimidine-2,4(1H,3H)-dione (5e): M.p. 228 ± 2298 ([15]: 230.5 ± 231.58). UV (EtOH):
273 (4.10). UV (pH 13): 273 (3.99). IR: 3022, 1688, 1655, 1513, 1494, 1464, 1248, 1171, 977, 827. 1H-NMR

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((D6)DMSO): 3.79 (s, 3 H); 5.66 (d, J ˆ 8.0, 1 H); 7.02 (d, J ˆ 8.7, 2 H); 7.48 (d, J ˆ 8.7, 2 H); 7.68 (d, J ˆ 8.0,
1 H); 11.43 (br., NH).
5-Methyl-1-phenylpyrimidine-2,4(1H,3H)-dione (5f): M.p. 198 ± 2008 ([17]: 1998). UV (EtOH): 273 (4.09).
UV (pH 13): 274 (3.99). IR: 3168, 3102, 1704, 1665, 1596, 1491, 1447, 1372, 1319, 1302, 1280, 1037, 761, 692.
1H-NMR ((D6)DMSO): 1.81 (d, J ˆ 1.2, 3 H); 7.40 ± 7.43 (m, 3 H); 7.47 ± 7.51 (m, 2 H); 7.61 (d, J ˆ 1.2,
HÀC(6)); 11.42 (br., NH).
5-Methyl-1-(4-methylphenyl)pyrimidine-2,4(1H,3H)-dione (5g): M.p. 216 ± 2178. UV (EtOH): 275 (4.07).
UV (pH 13): 275 (3.97). IR: 3156, 3103, 1702, 1669, 1517, 1465, 1425, 1367, 1299, 1284, 1178, 911, 823, 795, 756,
1
657. H-NMR ((D6)DMSO): 1.80 (d, J ˆ 1.2, 3 H); 2.50 (s, 3 H); 7.27 (s, 4 H); 7.56 (d, J ˆ 1.2, HÀC(6)); 11.38
‡
(br., NH). MS: 216 (95.41, M ), 173 (59.51), 144 (100), 130 (43.36), 118 (14.17), 91 (43.05). Anal. calc. for
C12H12N2O2: C 66.66, H 5.59, N 12.95; found: C 66.44, H 5.66, N 12.77.
5-Methyl-3-(4-methylphenyl)pyrimidine-2,4(1H,3H)-dione (5g'): M.p. 246 ± 2488 ([18]: no m.p. reported).
UV (EtOH): 264 (4.05). UV (pH 13): 292 (4.10). IR: 3273, 3069, 2925, 1712, 1659, 1479, 1433, 1219, 1189, 818,
767. 1H-NMR ((D6)DMSO): 1.80 (s, 3 H); 2.34 (s, 3 H); 7.06 (d, J ˆ 8.2, 2 H); 7.24 (d, J ˆ 8.0, 2 H); 7.39(m, 1 H);
‡
11.01 (br., NH). MS: 216 (75.27, M ), 133 (100), 105 (14.67), 83 (11.53), 55 (51.92), 54 (18.72).
1-(4-Bromophenyl)-5-methylpyrimidine-2,4(1H,3H)-dione (5h): M.p. 240 ± 2418. UV (EtOH): 272 (4.12).
UV (pH 13): 273 (4.02). IR: 3161, 3093, 1718, 1661, 1491, 1403, 1363, 1313, 1294, 1067, 1010, 915, 818, 715.
1H-NMR ((D6)DMSO): 1.80 (d, J ˆ 1.0, 3 H); 7.40 (d, J ˆ 8.8, 2 H); 7.61 (d, J ˆ 1.2, HÀC(6)); 7.69 (d, J ˆ 8.8,
‡
‡
2 H); 11.46 (br., NH). MS: 282 (45.80, [M ‡ 2] ), 280 (46.19, M ), 239 (33.27), 237 (36.04), 210 (29.38), 208
(29.81), 158 (35.19), 157 (20.21), 130 (100). Anal. calc. for C11H9BrN2O2: C 46.98, H 3.23, N 9.96; found: C 47.14,
H 3.35, N 9.94.
3-(4-Bromophenyl)-5-methylpyrimidine-2,4(1H,3H)-dione (5h'): M.p. 2628 (dec.). UV (EtOH): 265 (4.08).
1
UV (pH 13): 294 (4.14). IR: 3236, 2969, 1716, 1654, 1487, 1424, 1225, 1015, 769. H-NMR ((D6)DMSO): 1.81
(s, 3 H); 7.20 (d, J ˆ 8.5, 2 H); 7.42 (d, J ˆ 6.0, 1 H); 7.64 (d, J ˆ 8.5, 2 H); 11.05 (br., NH). MS: 282 (16.24, [M ‡
‡
‡
2] ), 280 (16.27, M ), 199 (10.34), 197 (10.78), 90 (18.23), 83 (30.85), 55 (100), 54 (24.93).
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ReceivedOctober 9, 2004