A mild and efficient method for N-arylnucleobase synthesis via the cross-coupling reactions of nucleobases with arylboronic acids catalyzed by simple copper salts

Article abstract of DOI:10.1002/hlca.200890107

A simple and efficient copper-salt catalyzed N-arylation of nucleobases is reported. In a mixed solvent of MeOH and H₂O, the coupling products were obtained in moderate to excellent yields at room temperature within a short time. Avariety of su

Full text of DOI:10.1002/hlca.200890107

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Helvetica Chimica Acta – Vol. 91 (2008)
A Mild and Efficient Method for N-Arylnucleobase Synthesis via the Cross-
Coupling Reactions of Nucleobases with Arylboronic Acids Catalyzed by
Simple Copper Salts
by Lan Taoa), Yang Yuea), Ji Zhanga), Shan-Yong Chena), and Xiao-Qi Yu*a)b)
a) Department of Chemistry, Key Laboratory of Green Chemistry and Technology (Ministry of
Education), Sichuan University, Chengdu, 610064, P. R. China
b) State Key Laboratory of Biotherapy, West China Hospital, West China Medical School,
Sichuan University, Chengdu, 610041, P. R. China (fax: þ 862885415886; e-mail: xqyu@tfol.com)
A simple and efficient copper-salt catalyzed N-arylation of nucleobases is reported. In a mixed
solvent of MeOH and H2O, the coupling products were obtained in moderate to excellent yields at room
temperature within a short time. Avariety of substituted N-aryl nucleobases can be prepared through this
procedure.
Introduction. – Because of the significant pharmaceutical, biological, and chemical
activities, there has been a growing interest in the modification of nucleobases in recent
years. Among these methods, N-arylation is a convenient way to prepare N-aryl
nucleobases. The classical method for the preparation of 9-aryl purines was based on
heterocyclization [1][2], and there was only one reported method for the synthesis of
N-arylpyrimidine by diphenyliodonium salts [3]. Both above routes were not
satisfactory because of their numerous steps or low yields.
In 1998, Chan et al. [4], Lam et al. [5], and Evans et al. [6] reported the copper-
mediated carbon – heteroatom cross-coupling reactions of boronic acids using a wide
range of different nucleophiles (NÀH containing substrates). And then, a Cu-
mediated N-arylation under very mild conditions employing arylboronic acids was
developed [7 – 12] and used for N-arylation of nucleobases [13 – 16].
Schultz and co-workers [13] reported the reaction of 2,6-dichloro-9H-purine with
boronic acids in the presence of cupric acetate and NEt3. The reaction resulted in the
desired N9-aryl product, however, the reaction could only be monitored by LC/MS
because of difficulties in isolation. Two years later, Gundersen and Bakkestuen [14]
accomplished the regioselective N9-arylation of various purine derivatives with
arylboronic acids, but the N-arylation of adenine was not successful under their
anhydrous reaction conditions. To improve the solubility of the substrate and to prevent
diarylation or triarylation, Gothelf and co-workers [16] used readily available protected
or masked nucleobases in the Cu-mediated N-arylation and N-alkenylation with
boronic acids. Nevertheless, it was not a general process because too many steps were
involved.
We have developed an efficient, facile, and mild method for the synthesis of N-
arylnucleobases in our previous work [17]. In this paper, the reactions of nucleobases
ꢀ 2008 Verlag Helvetica Chimica Acta AG, Zürich

Helvetica Chimica Acta – Vol. 91 (2008)
1009
(including cytosine, adenine, uracil, and thymine) were performed with arylboronic
acids in the presence of cupric acetate, base, and air. The reactions with guanine were
unsuccessful due to the poor solubility.
Results and Discussion. – Initial reactions were carried out with cytosine as N-
nucleophile and phenylboronic acid as the aryl donor. The effect of reaction solvent,
bases, ligands, and reaction temperature were investigated in this work, and the results
were consistent with our previous work [17].
Generally, the coupling reactions of N-heterocycles with arylboronic acids were
performed under anhydrous conditions [18]. However, we found, that when a small
quantity of H2O (MeOH/H2O 8 :1) was added, the coupling yield was increased to
44%. When we increased the amount of H2O to a 4 :1 ratio of MeOH/H2O, the yield
was up to 90%. Further increasing the amount of H2O led to the decrease of the yield.
Thus, the mixed solvent with a 4 :1 ratio of MeOH/H2O was the optimum solvent for
the coupling of cytosine with arylboronic acid [17]. TMEDA was found to be a suitable
base for the reaction, and room temperature was found to be the best reaction
temperature. The result of the reaction catalyzed by Cu(OAc)2 was slightly better than
that catalyzed by other copper salts. The equivalent of phenylboronic acid also affected
the result. The reaction with an equimolar ratio of nucleobase and PhB(OH)2 gave only
67% yield. Increasing the amount of phenylboronic acid led to high yields of required
product [17].
Table. CouplingReaction of Nucleobases with Various Substituted Phenylboronic Acids
Entry
Product (yield [%])
(¼ ArB(OH)2)
R1
R2
R3
ArÀC
ArÀA
ArÀUAr
ÀT
1
2
3
4
5
6
7
8
H
H
H
H
MeO
Br
H
H
H
H
H
Me
H
H
Me
MeO
Br
5a (90)a)
5b (83)a)
5c (48)
6a (85)a)
6b (28)
6c (25)
7a (63)
7b (40)
7c (43)
7d (66)
7e (54)
7f (61)
7g (56)
7h (53)
8a (59)
8b (33)
8c (35)
8d (51)
8e (46)
8f (52)
8g (53)
8h (52)
Me
MeO
H
H
H
5d (53)a)
5e (74)a)
5f (85)a)
5g (82)a)
5h (68)a)
6d (61)
6e (52)
6f (55)
H
H
6g (66)a)
6h (60)a)
a) Data taken from [17].
Several substituted arylboronic acids and some other nucleobases were applied to
the reaction under optimized conditions (Scheme 1), the results are shown in the Table.
The results did not reveal any obvious trends for either electron-rich or electron-poor
aryl boronic acids. The lower yields afforded by the ortho-substituted arylboronic acids
compared to para-substituted or unsubstituted phenylboronic acids might be attributed
to the steric hindrance at the reaction center.
Cytosine is superior to uracil and thymine as nucleobase in the coupling reaction,
and the reactions involving cytosine were complete within 45 min. Longer reaction

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Helvetica Chimica Acta – Vol. 91 (2008)
Scheme 1. Preparation of Cross-CouplingProducts
times were needed when uracil and thymine were employed in this catalytic coupling.
Stirring overnight at room temperature might be a good choice for these substrates.
Since the N-arylated purines could serve as ligands and coordinate to CuII [19 – 22], the
yields of the reactions involving adenine were moderate. It has been reported that
arylboronic acids could be oxidized by CuII in the presence of H2O to form the
corresponding phenols [23], which could be subsequently converted into quinone-type
derivatives [24]. Moreover, arylboronic acids could undergo deboronation in the
presence of H2O. These factors, together with a long reaction time resulted in
diminished yields. Increase of the mole amount of arylboronic acid might lead to the
appearance of di-arylated products, and the yield of the desired product did not
increase. For example, by using a 4 :1 mole ratio of arylboronic acid/thymine, after
stirring overnight, two products could be separated by column chromatography
1
(Scheme 2), the structure of product 10 was characterized by H-NMR and ESI-MS.
Conclusions. – In summary, we have developed a mild and efficient approach for the
direct N-arylation of nucleobases with arylboronic acids catalyzed by simple copper
salts. This reaction is cost-effective, easy to handle, and does not need an inert
atmosphere. This methodology should be tolerant to many sensitive functional groups
and gives the corresponding coupling products in moderate to excellent yields.

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Scheme 2
Experimental Part
General. Unless otherwise indicated, all reagents and solvents were obtained from commercial
suppliers and used without further purification. Anh. Et2O was dried and purified under N2 with K/
benzophenone and distilled immediately before use. TMEDA and TEA were distilled before use. IR:
Shimadzu FT-IR-4200 spectrometer; KBr pellets or thin films on KBr plates; in cmÀ1. 1H-NMR: Varian
INOVA-400 spectrometer; d in ppm, referenced to residual solvent peaks or internal tetramethylsilane
(TMS); J in Hz. ESI-MS: Finnigan LCQDECA mass spectrometer; J in m/z. HR-MS: Bruker Daltonics Bio
TOF; J in m/z.
General Procedure for the Cross-CouplingReaction. 1 (0.0556 g, 0.5 mmol), 9 (1 mmol), Cu(OAc)2 ·
H2O (0.099 g, 0.5 mmol), TMEDA (150 ml, 1 mmol), MeOH (40 ml), and H2O (10 ml) were placed in a
100 ml flask. The mixture was vigorously stirred under an atmosphere of air at r.t. for 45 min. The
solvents were evaporated, and the product purified by flash column chromatography (CC) on SiO2
(CH2Cl2/MeOH, 5 :1) to give the desired N-arylcytosine. For a mole ratio of arylboronic acid/thymine
4 :1, after stirring 24 h at r.t., the side product could be separated by CC.
The following compounds were prepared according to the General Procedure except for the reaction
time (for cytosine and adenine, 45 min; for uracil and thymine, over night).
1-Phenylcytosine (5a; data from [17], for comparison): White powder. M.p. 3008. IR (neat): 3334,
1
3066, 1638, 1486, 1372, 1294, 1174, 1128, 784, 698. H-NMR (400 MHz, (D6)DMSO): 5.79 (d, J ¼ 8.0,
CH); 7.24 (s, NH); 7.32 (s, NH); 7.34 – 7.38 (m, 3 arom. H); 7.45 (t, J ¼ 7.6, 2 arom. H); 7.63 (d, J ¼ 8.0,
CH). 13C-NMR (200 MHz, (D6)DMSO): 94.26; 126.75; 127.50; 128.99; 141.46; 146.03; 154.93; 166.21.
ESI-MS: 188.3 ([M þ H]þ). HR-ESI-MS: 188.0822 ([M þ H]þ, C10H10N3Oþ; calc. 188.0818).
1-(2-Methylphenyl)cytosine (5b): IR (neat): 3324, 3092, 1632, 1478, 1372, 1294, 1134, 992, 786, 726,
690. 1H-NMR (400 MHz, (D6)DMSO): 2.07 (s, Me); 5.77 (d, J ¼ 8.0, CH); 7.14 – 7.18 (m, NH2); 7.25 – 7.33
(m, 4 arom. H); 7.47 (d, J ¼ 8.0, CH). ESI-MS: 202.1 ([M þ H]þ).
1-(2-Methoxy-4-methylphenyl)cytosine (5c): IR (neat): 3318, 3085, 1647, 1450, 1369, 1301, 1130, 1034,
784, 731. 1H-NMR (400 MHz, (D6)DMSO): 2.25 (s, Me); 3.70 (s, Me); 5.71 (d, J ¼ 8.0, CH); 6.97 – 7.37
(m, NH2, 3 arom. H); 7.41 (d, J ¼ 8.0, CH). ESI-MS: 232.9 ([M þ H]þ).
1-(3-Methoxyphenyl)cytosine (5d): IR (neat): 3342, 3094, 1636, 1484, 1374, 1296, 1216, 800, 698.
1H-NMR (400 MHz, (D6)DMSO): 3.77 (s, Me); 5.78 (d, J ¼ 5.2, CH); 6.89 – 6.95 (m, 3 arom. H); 7.24 (s,
NH); 7.30 (s, NH); 7.35 (t, J ¼ 7.8, 1 arom. H); 7.61 (d, J ¼ 7.2, CH). ESI-MS: 218.0 ([M þ H]þ).
1-(3-Bromophenyl)cytosine (5e): IR (neat): 3338, 3094, 1636, 1584, 1476, 1374, 1298, 1136, 1088, 798,
692. 1H-NMR (400 MHz, (D6)DMSO): 5.79 (d, J ¼ 7.2, CH); 7.30 – 7.43 (m, 4 H); 7.55 – 7.62 (m, 2 arom.
H); 7.65 (d, J ¼ 7.8, CH). ESI-MS: 267.9 ([M þ H]þ).
1-(4-Methylphenyl)cytosine (5f): IR (neat): 3346, 3110, 1636, 1484, 1372, 1294, 1130, 798, 716.
1H-NMR (400 MHz, (D6)DMSO): 2.33 (s, Me); 5.77 (d, J ¼ 7.6, CH); 7.19 – 7.25 (m, 6 H); 7.58 (d, J ¼ 7.2,
CH). ESI-MS: 202.3 ([M þ H]þ).
1-(4-Methoxyphenyl)cytosine (5g): IR (neat): 3341, 3094, 1628, 1478, 1372, 1296, 1246, 1182, 1132,
1028, 992, 838, 786, 726. 1H-NMR (400 MHz, (D6)DMSO): 3.78 (s, Me); 5.76 (d, J ¼ 5.2, CH); 6.97 – 7.00
(m, NH2); 7.15 – 7.32 (m, 4 arom. H); 7.58 (d, J ¼ 7.2, CH). ESI-MS: 218.3 ([M þ H]þ).

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1-(4-Bromophenyl)cytosine (5h): IR (neat): 3354, 3068, 1634, 1484, 1376, 1298, 1132, 1068, 994, 798,
714. 1H-NMR (400 MHz, (D6)DMSO): 5.80 (d, J ¼ 7.6, CH); 7.29 – 7.37 (m, 4 H); 7.62 – 7.66 (m, 3 arom.
H). ESI-MS: 266.2 ([M þ H]þ).
9-Phenyladenine (6a): IR (neat): 3297, 3126, 1672, 1600, 1510, 1416, 1374, 1306, 1264, 1186, 1102, 964,
756. 1H-NMR (400 MHz, (D6)DMSO): 7.43 – 7.47 (m, 3 H); 7.60 (t, J ¼ 7.8, 2 arom. H); 7.91 (d, J ¼ 7.6, 2
arom. H); 8.22 (s, CH); 8.60 (s, CH). ESI-MS: 212.2 ([M þ H]þ).
9-(2-Methylphenyl)adenine (6b): IR (neat): 3370, 3275, 3044, 2918, 2850, 1702, 1612, 1514, 1474, 1377,
762, 736. 1H-NMR (400 MHz, (D6)DMSO): 2.15 (s, Me); 5.77 (s, NH2); 7.14 – 7.51 (m, 4 arom. H); 7.87 (s,
CH); 8.36 (s, CH). ESI-MS: 226.1 ([M þ H]þ).
9-(2-Methoxy-4-methylphenyl)adenine (6c): IR (neat): 3312, 3147, 2948, 2923, 2845, 1667, 1601, 1523,
1463, 776, 639. 1H-NMR (400 MHz, (D6)DMSO): 2.31 (s, Me); 3.73 (s, Me); 7.17 (d, J ¼ 9.2, 1 arom. H);
7.27 (s, NH2); 7.30 (t, J ¼ 2.4, 2 arom. H); 8.10 (s, CH); 8.19 (s, CH). ESI-MS: 256.8 ([M þ H]þ).
9-(3-Methoxyphenyl)adenine (6d): IR (neat): 3299, 3145, 3027, 2924, 2854, 1669, 1607, 1518, 1463,
1
957, 815, 672. H-NMR (400 MHz, (D6)DMSO): 2.38 (s, Me); 7.37 – 7.39 (m, NH2, 2 arom. H); 7.76 (d,
J ¼ 8.4, 2 arom. H); 8.10 (s, CH); 8.19 (s, CH). ESI-MS: 226.0 ([M þ H]þ).
9-(3-Bromophenyl)adenine (6e): IR (neat): 3308, 3152, 2910, 1671, 1597, 1509, 1482, 1299, 1186, 763,
685. 1H-NMR (400 MHz, (D6)DMSO): 7.40 (s, NH2); 7.59 – 7.61 (m, 2 arom. H); 7.90 (d, J ¼ 9.2, 2 arom.
H ); 8.21 (s, CH); 8.59 (s, CH). ESI-MS: 291.8 ([M þ H]þ).
9-(4-Methylphenyl)adenine (6f): IR (neat): 3306, 3150, 2967, 2850, 1672, 1605, 1509, 1491, 1370, 983,
828, 678. 1H-NMR (400 MHz, (D6)DMSO): 2.51 (s, Me); 7.39 (s, NH2); 7.46 – 7.52 (m, 4 arom. H); 8.21 (s,
CH); 8.62 (s, CH). ESI-MS: 226.1 ([M þ H]þ).
9-(4-Methoxyphenyl)adenine (6g): IR (neat): 3307, 3128, 1683, 1615, 1504, 1483, 1420, 1341, 1298,
1235, 1182, 1014, 961, 835. 1H-NMR (400 MHz, (D6)DMSO): 3.83 (s, Me); 7.13 (d, J ¼ 7.6, 2 arom. H);
7.36 (s, NH2); 7.76 (d, J ¼ 7.2, 2 arom. H); 8.18 (s, CH); 8.48 (s, CH). ESI-MS: 242.1 ([M þ H]þ).
9-(4-Bromophenyl)adenine (6h): IR (neat): 3294, 3124, 1682, 1604, 1524, 1474, 1418, 1382, 1338,
1302, 1248, 1176, 1104, 1032, 964, 832, 794, 736. 1H-NMR (400 MHz, (D6)DMSO): 7.43 (s, NH2); 7.78 –
7.81 (m, 2 arom. H); 7.90 – 7.93 (m, 2 arom. H); 8.22 (s, CH); 8.62 (s, CH). ESI-MS: 291.1 ([M þ H]þ).
1-Phenyluracil (7a): IR (neat): 3446, 3227, 3175, 3091, 2964, 1740, 1627, 1488, 1416, 1188, 826, 761,
1
696. H-NMR (400 MHz, CDCl3): 5.84 (d, J ¼ 7.6, CH); 7.11 (d, J ¼ 4.4, 1 arom. H); 7.13 (d, J ¼ 7.6, 1
arom. H); 7.24 (t, J ¼ 9.4, 1 arom. H); 7.46 (t, J ¼7.2, 1 arom. H); 7.52 (t, J ¼ 7.4, 1 arom. H); 7.64 (t, J ¼
7.2, CH); 10.11 (s, NH). HR-ESI-MS: 211.0472 ([M þ Na]þ, C10H8N2NaO2þ ; calc. 211.0478).
1-(2-Methylphenyl)uracil (7b): IR (neat): 3421, 3178, 3074, 2961, 1702, 1681, 1437, 1385, 1281, 835,
704. 1H-NMR (400 MHz, CDCl3): 2.25 (s, Me); 5.82 (d, J ¼ 7.6, CH); 7.18 (d, J ¼ 8, CH); 7.31 – 7.41 (m, 4
arom. H); 8.52 (s, NH). ESI-MS: 201.7 ([M À H]À).
1-(2-Methoxy-4-methylphenyl)uracil (7c): IR (neat): 3426, 3150, 3043, 2924, 2840, 1700, 1623, 1513,
1455, 1378, 1300, 1241, 806, 763. 1H-NMR (400 MHz, CDCl3): 2.32 (s, Me); 3.81 (s, Me); 5.75 (d, J ¼ 7.6,
CH); 6.92 (d, J ¼ 8.4, 1 arom. H); 7.08 (s, 1 arom. H); 7.14 (d, J ¼ 8, 1 arom. H); 7.21 (d, J ¼ 8, CH); 8.73
(s, NH). ESI-MS: 233.0 ([M þ H]þ).
1-(3-Methoxyphenyl)uracil (7d): IR (neat): 3433, 3265, 3140, 3095, 2968, 2840, 1731, 1640, 1488, 1421,
1
1320, 1232, 1193, 790, 692. H-NMR (400 MHz, CDCl3): 3.82 (s, Me); 5.86 (d, J ¼ 9.2, CH); 6.78 (s, 1
arom. H); 6.83 (d, J ¼ 9.6, 1 arom. H); 6.98 – 7.01 (m, 1 arom. H); 7.16 – 7.20 (m, 1 arom. H); 7.42 (t, J ¼
8.2, CH); 9.68 (s, NH). ESI-MS: 219.7 ([M þ H]þ).
1-(3-Bromophenyl)uracil (7e): IR (neat): 3365, 3203, 3195, 3099, 2964, 1730, 1669, 1472, 1416, 1381,
1247, 1182, 803, 764, 688. 1H-NMR (400 MHz, CDCl3): 5.84 (d, J ¼ 9.2, CH); 7.11 – 7.27 (m, 2 arom. H);
7.41 (d, J ¼ 4.8, 1 arom. H); 7.50 – 7.60 (m, 1 arom. H, 1 CH); 10.11 (s, NH). ESI-MS: 266.7 ([M þ H]þ).
1-(4-Methylphenyl)uracil (7f): IR (neat): 3375, 3233, 3171, 3081, 2970, 2915, 1741, 1637, 1418, 1388,
1
1187, 819, 761, 713. H-NMR (400 MHz, CDCl3): 2.41 (s, Me); 5.84 (d, J ¼ 9.2, CH); 7.12 (d, J ¼ 8.4,
1 CH, 1 arom. H); 7.15 (d, J ¼ 7.6, CH); 7.32 (d, J ¼ 8, 2 arom. H); 10.04 (s, NH). ESI-MS: 203.8
([M þ H]þ).
1-(4-Methoxyphenyl)uracil (7g): IR (neat): 3438, 3255, 3191, 3115, 2966, 1742, 1638, 1517, 1420, 1109,
1
936, 807. H-NMR (400 MHz, CDCl3): 3.84 (s, Me); 5.86 (d, J ¼ 9.2, CH); 7.02 (d, J ¼ 6.4, 2 arom. H);
7.14 – 7.19 (m, 2 arom. H, 1 CH); 9.68 (s, NH). ESI-MS: 218.9 ([M þ H]þ).

Helvetica Chimica Acta – Vol. 91 (2008)
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1-(4-Bromophenyl)uracil (7h): IR (neat): 3446, 3234, 3169, 3091, 2966, 1741, 1627, 1589, 1417, 1386,
1069, 827, 760. 1H-NMR (400 MHz, CDCl3): 5.87 (d, J ¼ 8, CH); 7.13 (d, J ¼ 8.4, 2 arom. H); 7.18 (d, J ¼
7.6, CH); 7.64 (d, J ¼ 8.4, 2 arom. H); 9.91 (s, NH). ESI-MS: 266.7 ([M À H]À).
1-Phenylthymine (8a): IR (neat): 3430, 3292, 3175, 3065, 2925, 1704, 1651, 1491, 1422, 1216, 768, 698.
1H-NMR (400 MHz, CDCl3): 1.93 (s, Me); 7.01 – 7.12 (m, 3 arom. H); 7.26 (s, CH); 7.63 (d, J ¼ 8.4, 2
arom. H); 9.76 (s, NH). ESI-HR-MS: 225.0642 ([M þ Na]þ, C11H10N2NaO2þ ; calc. 225.0634).
1-(2-Methylphenyl)thymine (8b): IR (neat): 3411, 3276, 3066, 2926, 2838, 1688, 1654, 1459, 1385,
1297, 765, 711. 1H-NMR (400 MHz, CDCl3): 1.94 (s, Me); 2.25 (s, Me); 7.02 (s, CH); 7.19 (d, J ¼ 8, 1 arom.
H); 7.31 – 7.37 (m, 3 arom. H); 8.51 (s, NH). ESI-MS: 216.8 ([M À H]À).
1-(2-Methoxy-4-methylphenyl)thymine (8c): IR (neat): 3421, 3164, 3035, 2921, 2830, 1716, 1664, 1516,
1464, 1302, 1288, 812. 1H-NMR (400 MHz, CDCl3): 1.94 (s, Me); 2.31 (s, Me); 3.81 (s, Me); 6.91 (d, J ¼
10.8, 1 arom. H); 6.98 (s, 1 arom. H); 7.06 (s, CH); 7.19 (d, J ¼ 8, 1 arom. H); 8.65 (s, NH). ESI-MS: 247.0
([M þ H]þ).
1-(3-Methoxyphenyl)thymine (8d): IR (neat): 3446, 3218, 3075, 2948, 1719, 1647, 1494, 1431, 1292,
1231, 1196, 810, 765, 695. 1H-NMR (400 MHz, CDCl3): 1.94 (s, Me); 3.81 (s, Me); 6.76 (s, 1 arom. H); 6.82
(d, J ¼ 7.6, 1 arom. H); 6.97 (d, J ¼ 5.6, 1 arom. H); 7.04 (s, CH); 7.41 (t, J ¼ 8.2, 1 arom. H); 9.53 (s, NH).
ESI-MS: 231.8 ([M À H]À).
1-(3-Bromophenyl)thymine (8e): IR (neat): 3441, 3245, 3185, 3100, 2925, 1719, 1654, 1474, 1425,
1221, 1139, 768, 685. 1H-NMR (400 MHz, CDCl3): 1.92 (s, Me); 6.99 (s, 1 arom. H); 7.18 (d, J ¼ 6, 1 arom.
H); 7.40 (s, CH); 7.50 (t, J ¼ 11.4, 1 arom. H); 10.03 (s, NH). ESI-MS: 280.8 ([M À H]À).
1-(4-Methylphenyl)thymine (8f): IR (neat): 3334, 3208, 3065, 2925, 1703, 1650, 1428, 1230, 815, 763.
1H-NMR (400 MHz, CDCl3): 1.91 (s, Me); 2.39 (s, Me); 6.97 (d, J ¼ 6.8, 1 arom. H); 7.10 (d, J ¼ 10.4, 2
arom. H); 7.29 (s, 1 arom. H); 7.31 (s, CH); 10.13 (s, NH). ESI-MS: 215.9 ([M À H]À).
1-(4-Methoxyphenyl)thymine (8g): IR (neat): 3446, 3208, 3163, 3103, 2922, 2838, 1707, 1646, 1512,
1
1435, 1247, 834, 769. H-NMR (400 MHz, CDCl3): 1.92 (s, Me); 3.84 (s, Me); 7.00 – 7.02 (m, 2 arom. H,
1 CH); 7.14 (d, J ¼ 8.4, 2 arom. H); 9.90 (s, NH). ESI-MS: 255.1 ([M þ Na]þ).
1-(4-Bromophenyl)thymine (8h): IR (neat): 3398, 3289, 3234, 3135, 3067, 2983, 1735, 1652, 1589,
1420, 1353, 1231, 1066, 829, 767. 1H-NMR (400 MHz, CDCl3): 1.93 (s, Me); 7.01 (d, J ¼ 6.8, 1 arom. H);
7.11 (d, J ¼ 8.8, 2 arom. H); 7.62 – 7.65 (m, 1 arom. H, 1 CH); 9.91 (s, NH). ESI-MS: 280.8 ([M À H]À).
This work was financially supported by the National Natural Science Foundation of China (Nos.
20725206, 20732004, and 20572075), Program for New Century Excellent Talents in University, Specialized
Research Fund for the Doctoral Program of Higher Education, and Scientific Fund of Sichuan Province
for OutstandingYoungScientists.
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Received November 27, 2007