Synthesis of substituted uracils by the reactions of halouracils with selenium, sulfur, oxygen and nitrogen nucleophiles under focused microwave irradiation

Article abstract of DOI:10.1016/j.tet.2005.01.085

Under microwave irradiation, the nucleophilic substitution reactions of halouracils with selenium, sulfur, oxygen and nitrogen nucleophiles was complete within several minutes with yields up to 99%. The method using microwave irradiation is superior to th

Full text of DOI:10.1016/j.tet.2005.01.085

Tetrahedron 61 (2005) 3107–3113
Synthesis of substituted uracils by the reactions of halouracils with
selenium, sulfur, oxygen and nitrogen nucleophiles under focused
microwave irradiation
*
Woei-Ping Fang, Yuh-Tsyr Cheng, Yann-Ru Cheng and Yie-Jia Cherng
Department of Safety Health and Environmental Engineering, Chung-Tai Institute of Health Science and Technology,
Taichung 40605, Taiwan
Received 4 October 2004; accepted 6 January 2005
Abstract—Under microwave irradiation, the nucleophilic substitution reactions of halouracils with selenium, sulfur, oxygen and nitrogen
nucleophiles was complete within several minutes with yields up to 99%. The method using microwave irradiation is superior to those
conducted under conventional heating processes.
q 2005 Elsevier Ltd. All rights reserved.
1. Introduction
appeared to decrease in the order of BrOClOFOI
(compared entries 1, 2, 4 with 5 in Table 1). There is little
regularity in the relative replaceabilities of these sub-
stituents. The reason might be that iodine is too soft to react
with hard nitrogen nucleophile.4 As a comparison (entry 3,
Table 1), 5-chlorouracil was heated with 20 equiv of
benzylamine at 150 8C in an oil bath for 20 min to give
only 34% yield of 5-benzylaminouracil, far less than 88% in
microwave irradiation (entry 2, Table 1). We have now
found that 5-substituted aminouracils were prepared by
reaction of 5-bromouracil with appropriate amine in
95–98% yield within 10 min under microwave irradiation
(Table 1, entries 8–12). Weak nucleophilic aromatic amine
such as aniline also can react with 5-bromouracil to give
5-anilinouracil (92% yield) at 180 8C within 15 min
(Table 1, entry 13). By conventional heating process,
5-anilinouracil was prepared at 195 8C in refluxing ethylene
glycol for 2 h (76% yield).5
Several of the 5- and 6-substituted uracils exhibit significant
antitumor activity against experimental mouse tumor.1
Therefore, an efficient synthetic methodology for the
preparation of these uracil derivatives will be crucial in
developing new antitumor drugs. Our previous results have
shown that the reaction rates of nucleophilic aromatic and
heteroaromatic substitution can be accelerated under
microwave irradiation.2,3 We have been interested in
developing new, more efficient, and synthetically useful
reactions for the synthesis of biologically active molecules
via microwave acceleration. As a result the development of
more practical synthesis of 5-substituted and 6-substituted
uracils will be examined in this proposal to further expand
the utility and scope of our previous studies.
2. Results and discussion
In order to investigate the efficacy of nucleophilic
substitutions in different reaction conditions, we examined
the solvent effect in the displacement reaction. 5-Chloro-
uracil, 5-bromouracil and 5-iodouracil were studied. When
reacted with PhSNa under microwave irradiation, the
substitution reaction could be realized by using NMP
(N-methylpyrrolidone), HMPA, DMSO, DMF and DMAC
(dimethylacetamide) as the solvent (Table 2). The better
yields were obtained in HMPA for 5-chlorouracil and
5-bromouracil (93 and 86%, respectively. Table 2, entries 2
and 7). However, the reaction of 5-iodouracil with 2.2 equiv
of PhSNa proceeded smoothly at 130 8C under microwave
Study was initiated of 5-bromouracil with amine nucleo-
philes. Microwave irradiation of 10 equiv of benzylamine
and 5-bromouracil at 110 8C is found to yield 5-benzyl-
aminouracil in 95% (Table 1, entry 1). The nucleophilic
substituted reactions of 5-iodouracil, 5-chlorouracil and
5-fluorouracil were similarly performed. Of the four
halouracils studied, the relative reactivity of 5-halouracils
toward nitrogen-containing nucleophile (benzylamine)
Keywords: Microwave irradiation; Nucleophilic substitution; Halouracils.
* Corresponding author. Tel.: C886 422391647x7044; fax: C886
422396761; e-mail: yjcherng@chtai.ctc.edu.tw
0040–4020/$ - see front matter q 2005 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2005.01.085

3108
W.-P. Fang et al. / Tetrahedron 61 (2005) 3107–3113
Table 1. Substitution of 5-halouracils with amines
Entry
X
Nucleophile
Solvent
Molar pro-
portions of
nucleophile
Temp (8C)
Time (min)
Product, RZ
Yield (%)
a
a
a
a
a
a
1
2
3
4
5
6
7
8
Br
Cl
Cl
F
I
I
NH2CH2Ph
NH2CH2Ph
NH2CH2Ph
NH2CH2Ph
NH2CH2Ph
NH2CH2Ph
NH2CH2Ph
NH2(CH2)3CH3
Piperidine
Morpholine
Cyclohexylamine
NH(CH3)CH2 Ph
PhNH2
10
20
20
20
20
10
3.5
20
20
20
20
15
15
110
150
150
170
130
100
130
90
90
90
110
120
180
12
20
20
20
10
10
10
10
9
5
7
5
15
NHCH2Ph
NHCH2Ph
NHCH2Ph
NHCH2Ph
NHCH2Ph
NHCH2Ph
NHCH2Ph
NH(CH2)3CH3
Piperidyl
N-Morpholyl
Cyclohexylamino
N (CH3) CH2 Ph
NHPh
95
88
34b
76
0
18
16
96
95
96
98
97
92
I
DMF
a
Br
Br
Br
Br
Br
Br
a
a
a
a
a
9
10
11
12
13
a No solvent was used.
b Heating in an oil bath.
Table 2. Reaction conditions of 5-halorouracils
Entry
X
Solvent
Molar pro-
portions of
nucleophile
Temp (8C)
Time (min)
Product, RZ
Yield (%)
1
2
3
4
5
6
7
8
Cl
Cl
Cl
Cl
Cl
Br
Br
Br
Br
Br
I
NMP
4
4
4
4
4
4
4
4
4
4
2.2
2.2
2.2
2.2
140
140
140
140
140
140
140
140
140
140
130
130
130
130
5
5
5
5
5
5
5
5
5
5
5
5
5
5
SPh
SPh
SPh
SPh
SPh
SPh
SPh
SPh
SPh
SPh
SPh
SPh
SPh
SPh
81
93
56
74
74
75
86
65
77
75
82
72
80
84
HMPA
DMSO
DMF
DMAC
NMP
HMPA
DMSO
DMF
DMAC
NMP
9
10
11
12
13
14
I
I
I
HMPA
DMSO
DMF
irradiation for 5 min in different solvents (Table 2, entries
11–14). Interestingly, the result indicated that DMF was the
best solvent.
similarly carried out (Table 3, entries 4–29). We might
expect that with 5-iodouracil the order of reactivity is
PhSeHOPhSNaOPhONa (compared entries 17, 21 with 29
in Table 3). Different 5-halouracils were studied in an
attempt to appreciate the leaving group effect on reactivity
and yields. Of the four halouracil tested, the relative
reactivity of 5-halouracils toward selenium nucleophile
(PhSeH) appeared to decrease in the order of IOBrOClOF
(compared entries 3, 10, 15 with 29 in Table 3). The relative
reactivity of 5-halouracils toward sulfur nucleophile
(PhSNa) appeared to decrease in the order of IOClwBrO
F (compared entries 2, 4, 12 with 22 in Table 3). Se and I are
more polarizable in nucleophiles and halogens. The iodine
would be expected to be easily attacked by nucleophilic
A detailed study of the reactions of 5-halouracils with O, S
and Se containing nucleophiles in various amounts, reaction
times, temperatures and solvents was investigated in order
to find the optimized conditions for the preparation of uracil
derivatives (Table 3). When 5-fluorouracil was treated with
the oxygen, sulfur and selenium nucleophiles (PhONa,
PhSNa and PhSeH) under microwave irradiation, the
corresponding 5-substituted uracils were obtained in low
yield (0–14%). The nucleophilic substitution reactions of
5-chlorouracil, 5-bromouracil and 5-iodouracil were

W.-P. Fang et al. / Tetrahedron 61 (2005) 3107–3113
Table 3. Reactions of 5-halouracil with nucleophiles
3109
Entry
X
Nucleophile
Solvent
Molar pro-
portions of
nucleophiles
Temp (8C)
Time (min)
Product, RZ
Yield (%)
1
2
3
4
5
6
7
8
F
F
F
PhONa
PhSNa
PhSeH
PhSNa
PhSNa
PhSNa
PhSNa
PhSNa
PhSNa
PhSeH
PhSeH
PhSNa
PhSNa
PhSNa
PhSeH
PhSeH
PhONa
PhSNa
PhSNa
PhSNa
PhSNa
PhSNa
PhSNa
PhSNa
PhSNa
PhSNa
PhSeH
PhSeH
PhSeH
NMP
4
4
4
2
4
4
4
4
4
4
4
2
4
4
4
4
3
4
3
2.5
2.2
2
2
2
2.2
2
3
2.5
2.3
140
180
180
130
130
130
140
150
150
150
160
130
140
140
150
130
160
130
130
130
130
130
130
130
130
130
130
130
130
5
OPh
SPh
SePh
SPh
SPh
SPh
SPh
SPh
SPh
SePh
SePh
SPh
SPh
SPh
SePh
SePh
OPh
SPh
SPh
SPh
SPh
SPh
SPh
SPh
SPh
SPh
SePh
SePh
SePh
0
HMPA
HMPA
NMP
30
20
5
5
5
5
5
5
5
10
5
5
5
5
5
20
5
5
5
5
5
5
5
5
5
5
5
17
14
51
84
86
93
97
36a
52
43
47
75
86
70
29
0
39
69
81
82
82
77
76
84
82
58
75
96
Cl
Cl
Cl
Cl
Cl
Cl
Cl
Cl
Br
Br
Br
Br
Br
I
I
I
I
I
I
I
I
I
NMP
HMPA
HMPA
HMPA
HMPA
HMPA
HMPA
NMP
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
NMP
HMPA
HMPA
DMF
NMP
NMP
NMP
NMP
NMP
NMP
HMPA
DMSO
DMF
DMF
DMF
I
I
I
I
DMF
DMF
5
a Heating in an oil bath.
selenium. So the trend of 5-halouracils toward selenium
nucleophile is predictable.
Under microwave irradiation, 6-chlorouracil also reacted
with PhSNa, PhSeH and some amino nucleophiles to give
the corresponding 6-substituted uracils in varied yields
(38–98%, Table 4). The reaction with PhSNa (4 equiv) in
HMPA and DMSO at 90 8C for 3 min afforded an
excellent yield of 6-phenylthiouracil (98 and 96%,
respectively. Table 4, entries 11 and 12). The substitution
with PhSeH was achieved in DMF to provide an 86%
yield of 6-phenylselenenyluracil (entry 18, Table 4). The
results indicated that the reactivity is 6-chlorouracilO5-
chlorouracil. For example, the substitution reaction of
6-chlorouracil with PhSNa occurred at 90 8C in 3 min
(98% yield, Table 4, entry 11), whereas the reaction of
5-chlorouracil occurred at 150 8C in 5 min (97% yield,
Table 3, entry 8).
The product yield could be improved by running the
reaction in a more polar solvent. The reaction of
5-chlorouracil with PhSNa afforded 5-phenylthiouracil in
the yield up to 97% (Table 3, entry 8). The dipolar solvent
HMPA might facilitate the substitution reaction. For
comparing the efficacy of microwave irradiation with
conventional heating, a HMPA solution of 5-chlorouracil
and PhSNa (4 equiv) was heated at 150 8C in an oil bath for
5 min to give only 36% yield of 5-phenylthiouracil, far less
than 97% in microwave irradiation (Table 3, entry 9). The
reaction with PhONa nucleophile failed to give any
appreciable quantities of the 5-phenoxyuracil in various
reaction conditions.
Similar experiments were performed with another two
substrates, 1,3-dimethyl-5-bromouracil and 1,3-dimethyl-6-
chlorouracil (Tables 5 and 6). 1,3-Dimethyl-5-bromouracil
was less reactive than 5-bromouracil toward nitrogen-
containing nucleophiles. Only the reaction with piperidine
gave the desired substitution product in a good yield of 94%
(entry 8, Table 5). When 1,3-dimethyl-6-chlorouracil was
treated with the sulfur, oxygen and nitrogen nucleophiles
(PhSNa, PhONa, EtONa, MeONa, aniline, benzylamine and
piperidine) under microwave irradiation, the corresponding
When 2.2 equiv of PhSNa or 2.3 equiv of PhSeH were used,
5-iodouracil was converted to 5-phenylthiouracil or 5-
(phenylselenenyl)uracil in good yields (84 and 96%,
respectively. Table 3, entries 25 and 29). However, the
yield of 5-phenylthiouracil or 5-(phenylselenenyl)uracil
deteriorated when greater quantities of PhSNa or PhSeH
were applied (Table 3, entries 18–22 and 27–29). Because
iodine is the most replaceable of the halogens, it does not
need too much amount of nucleophile.

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W.-P. Fang et al. / Tetrahedron 61 (2005) 3107–3113
Table 4. Substitutions of 6-chlorouracil with nucleophiles
Entry
Nucleophile
Solvent
Molar pro-
portions of
nucleophiles
Temp (8C)
Time (min)
Product, RZ
Yield (%)
a
a
a
a
a
a
a
a
1
2
3
4
5
6
7
8
NH2CH2Ph
NH2CH2Ph
NH2(CH2)3CH3
Cyclohexylamine
Piperidine
Morpholine
NH (CH3) CH2 Ph
PhNH2
PhONa
PhSNa
PhSNa
PhSNa
PhSNa
PhSNa
PhSeH
PhSeH
PhSeH
PhSeH
15
15
15
20
20
20
10
30
4
4
4
4
4
130
130
90
130
100
100
130
160
90
90
90
90
90
15
15
20
35
15
15
20
20
3
3
3
3
3
NHCH2Ph
NHCH2Ph
NH(CH2)3CH3
Cyclohexylamino
Piperidyl
N-Morpholyl
N (CH3) CH2 Ph
NHPh
OPh
SPh
SPh
SPh
SPh
SPh
SePh
SePh
SePh
SePh
94
41b
62
88
96
94
92
95
0
86
98
96
90
85
83
63
38
86
9
NMP
NMP
HMPA
DMSO
DMF
DMAC
NMP
HMPA
DMSO
DMF
10
11
12
13
14
15
16
17
18
4
4
4
4
90
90
90
90
3
3
4
4
4
90
4
a No solvent was used.
b Heating in an oil bath.
Table 5. Substitutions of 1,3-dimethyl-5-bromouracil with nucleophiles
Entry
Nucleophile
Solvent
Molar pro-
portions of
nucleophiles
Temp (8C)
Time (min)
Product, RZ
Yield (%)
1
2
3
4
5
6
7
8
PhSNa
PhSNa
PhSNa
PhSNa
PhONa
PhNH2
NH2CH2Ph
Piperidine
NMP
3
3
3
3
130
130
130
130
130
180
180
100
3
3
3
3
SPh
SPh
SPh
SPh
79
52
45
78
0
0
0
94
HMPA
DMSO
DMF
NMP
a
3
2
OPh
20
20
15
30
30
40
NHPh
NHCH2Ph
Piperidyl
a
a
a No solvent was used.
6-substituted uracils were obtained in excellent yields
(90–99%, Table 6).
desired products were obtained. For example, the substi-
tution reaction of 5-bromouracil with PhSNa by heating at
140 8C for 2 h gave a low yield (11%) of 5-phenylthio-
uracil,6 whereas the reaction was promoted significantly by
microwave irradiation at 140 8C for 5 min gave a good yield
(86%) of the desired product (Table 3, entry 14). The
relative reactivity of halouracils in substitution reactions
follows 1,3-dimethyl-6-chlorouracilO5-bromouracilO6-
chlorouracilO1,3-dimethyl-5-bromouracil. For example,
the reaction of 1,3-dimethyl-6-chlorouracil with PhONa
afforded 90% yield of the desired product under microwave
irradiation at 60 8C for 0.5 min (Table 6, entry 2).
3. Conclusion
In conclusion, our present study demonstrated that micro-
wave irradiation can greatly facilitate the synthesis of
various substituted uracils by nucleophilic substitution. This
new synthetic tool is definitely valuable for the quick access
of these bioactive compounds. The substitution reactions
under conventional heating take many hours and low yields

W.-P. Fang et al. / Tetrahedron 61 (2005) 3107–3113
Table 6. Substitutions of 1,3-dimethyl-6-chlorouracil with nucleophiles
3111
Entry
Nucleophile
Solvent
Molar proportions
of nucleophiles
Temp (8C)
Time (min)
Product, RZ
Yield (%)
1
2
3
4
5
6
7
8
PhSNa
PhONa
EtONa
MeONa
PhNH2
NH2CH2Ph
piperidine
NH (CH3) CH2 Ph
NMP
NMP
EtOH
MeOH
a
3
3
3
3
15
5
15
5
60
60
60
60
160
130
60
0.5
0.5
0.5
0.5
30
3
SPh
OPh
OEt
OMe
NHPh
NHCH2Ph
piperidyl
N (CH3) CH2 Ph
93
90
97
99
98
98
99
94
a
a
a
0.5
1
130
a No solvent was used.
4. Experimental
d 10.89 and 10.40 (2s, 2H, 2NH), 6.66 (s, 1H, 6-H), 2.71 (m,
4H), 1.54–1.43 (m, 6H).
1H NMR spectra were measured in DMSO-d6 or CDCl3
solutions on a Bruker 300 spectrometer. Reactions were
monitored by analytical thin-layer chromatography using
silica gel 60 F-254 (0.2 mm layer thickness). Flash
chromatography was carried out by utilizing silica gel 60
(70–230 mesh ASTM).
4.1.4. 5-Morpholinouracil.8 White solid, mp 329–334 8C
(dec) (lit. O310 8C); 1H NMR (300 MHz, DMSO-d6) d
11.05 and 10.46 (2s, 2H, 2NH), 6.72 (s, 1H, 6-H), 3.63 (t,
JZ4.5 Hz, 4H), 2.77 (t, JZ4.5 Hz, 4H).
4.1.5. 5-Cyclohexylaminouracil.8 Pale yellow solid, mp
327–333 8C (dec) (lit. O305 8C); 1H NMR (300 MHz,
DMSO-d6) d 11.13 and 10.15 (2s, 2H, 2NH), 6.36 (d, JZ
5.2 Hz, 1H, 6-H), 3.78 (d, JZ8.4 Hz, 1H, NH), 2.87 (m,
1H), 1.84–1.05 (m, 10H).
4.1. General procedure for reaction of halouracil
nucleophile
In a reaction vessel (12 mL) were placed a nucleophile and
a halouracil (0.1 mmol) in an appropriate solvent (1 mL).
t-BuOK (1.1 equiv vs. nucleophile) could be added as the
base if needed. The reaction vessel was then placed into the
cavity of a focused monomode microwave reactor (CEM
Discover) and irradiated for the period listed in the tables.
The reaction temperature was maintained by modulating the
power level of the reactor. The desired product precipitates
after the pH was adjusted to 6 with 6 N HCl. The product
was collected, washed with H2O. Then was purified by
recrystallization. Products 19, 21, 22, 23, 24, 26 and 27 were
purified by silica gel chromatography eluting with a mixture
of hexane, ethyl acetate and acetone.
4.1.6. 5-(Benzylmethylamino)uracil.8 White solid, mp
269–271 8C (lit. 267–269 8C); 1H NMR (300 MHz,
DMSO-d6) d 11.08 and 10.40 (2s, 2H, 2NH), 7.33–7.20
(m, 5H, Ph), 6.60 (s, 1H, 6-H), 4.04 (s, 2H), 2.39 (s, 3H).
4.1.7. 5-Anilinouracil.5 Pale white solid, mp 318–320 8C
(dec) (lit. 317–319 8C dec); 1H NMR (300 MHz, DMSO-d6)
d 11.25 (s, H, NH), 10.63 (d, JZ4.8 Hz, 1H, NH), 7.29 (d,
JZ5.8 Hz, 1H, 6-H), 7.12–6.62 (m, 5H, Ph), 6.90 (s, 1H,
NH).
4.1.8. 5-Phenylthiouracil.9 White solid, mp 273–274 8C
(lit. 269–271 8C); H NMR (300 MHz, DMSO-d6) d 11.40
(s, 2H, 2NH), 7.92 (s, 1H, 6-H), 7.29–7.14 (m, 5H, SPh).
1
4.1.1. 5-Benzylaminouracil.7 Pale white solid, mp
301–305 8C (dec) (lit. 285 8C dec); H NMR (300 MHz,
1
DMSO-d6) d 11.34 and 10.02 (2s, 2H, 2NH), 7.31–7.19 (m,
5H, Ph), 6.08 (s, 1H, 6-H), 4.97 (t, JZ6.2 Hz, 1H, NH), 4.08
(d, JZ6.2 Hz, 2H).
4.1.9. 5-Phenylselenenyluracil.9 White solid, mp
250–252 8C (lit. 249–251 8C); 1H NMR (300 MHz,
DMSO-d6) d 11.36 and 11.01 (2s, 2H, 2NH), 7.79 (s, 1H,
6-H), 7.36–7.19 (m, 5H, SePh).
4.1.2. 5-Butylaminouracil.8 Pale yellow solid, mp
285–288 8C (dec) (lit. 286–288 8C dec); 1H NMR
(300 MHz, DMSO-d6) d 11.11 and 10.13 (2s, 2H, 2NH),
6.26 (d, JZ6.0 Hz, 1H, 6-H), 4.10 (t, JZ5.8 Hz, 1H, NH),
2.76 (m, 2H), 1.47 (m, 2H), 1.30 (m, 2H), 0.87 (t, JZ7.4 Hz,
3H).
4.1.10. 6-Benzylaminouracil.10 Pale white solid, mp
318–320 8C (dec) (lit. 316–317 8C dec); 1H NMR
(300 MHz, DMSO-d6) d 10.19 and 10.03 (2s, 2H, 2NH),
7.38–7.24 (m, 5H, Ph), 6.60 (t, JZ5.7 Hz, 1H, NH). 4.37 (s,
1H, 5-H). 4.25 (d, JZ5.7 Hz, 2H, –CH2Ph).
4.1.3. 5-Piperidyluracil.8 White solid, mp 303–305 8C
(dec) (lit. 285–290 8C dec); 1H NMR (300 MHz, DMSO-d6)
4.1.11. 6-Cyclohexylaminouracil.11 Yellow solid, mp
327–329 8C (lit. 327–328 8C); 1H NMR (300 MHz,

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W.-P. Fang et al. / Tetrahedron 61 (2005) 3107–3113
DMSO-d6) d 10.15 and 9.66 (2s, 2H, 2NH), 6.03 (d, JZ
7.9 Hz, 1H, NH), 4.43 (s, 1H, 5-H), 3.18 (m, 1H), 1.83–1.14
(m, 10H).
4.1.23. 1,3-Dimethyl-6-methoxyuracil.17 Colorless
needles, mp 164–166 8C (lit. 165–166 8C); 1H NMR
(300 MHz, DMSO-d6) d 5.21 (s, 1H, 5-H), 3.86 (s, 3H),
3.20 (s, 3H), 3.12 (s, 3H).
4.1.12. 6-Piperidyluracil.12 White solid, mp 307–309 8C
(dec); H NMR (300 MHz, DMSO-d6) d 10.33 and 10.22
1
4.1.24. 1,3-Dimethyl-6-anilinouracil.18 Yellow solid, mp
186–188 8C (lit. 187 8C); 1H NMR (300 MHz, DMSO-d6) d
8.53 (s, 1H, NH), 7.45–7.21 (m, 5H, Ph), 4.62 (s, 1H, 5-H),
3.42 (s, 3H), 3.10 (s, 3H).
(2s, 2H, 2NH), 4.60 (s, 1H, 5-H), 3.23 (m, 4H), 1.51 (m,
6H).
4.1.13. 6-Morpholinouracil.13 White solid, mp 322–326 8C
1
4.1.25. 1,3-Dimethyl-6-benzylaminouracil.19 Colorless
needles, mp 159–163 8C (lit. 158–159 8C); 1H NMR
(300 MHz, DMSO-d6) d 7.55 (t, JZ5.9 Hz, NH),
7.34–7.21 (m, 5H, Ph), 4.49 (s, 1H, 5-H), 4.32 (d, JZ
5.9 Hz, 2H), 3.36 (s, 3H), 3.04 (s, 3H).
(dec) (lit. O310 8C); H NMR (300 MHz, DMSO-d6) d
11.45 and 10.24 (2s, 2H, 2NH), 4.65 (s, 1H, 5-H), 3.61 (t,
JZ4.8 Hz, 4H), 3.12 (t, JZ4.8 Hz, 4H).
4.1.14. 6-(Benzylmethylamino)uracil.11 White solid, mp
273–275 8C (lit. 273–275 8C); 1H NMR (300 MHz, DMSO-
d6) d 10.35 and 10.13 (2s, 2H, 2NH), 7.40–7.15 (m, 5H, Ph),
4.58 (s, 2H), 4.47 (s, 1H, 5-H), 2.92 (s, 3H).
4.1.26. 1,3-Dimethyl-6-piperidyluracil.20 Colorless solid,
mp 78–79 8C (lit. 77 8C); 1H NMR (300 MHz, DMSO-d6) d
5.10 (s, 1H, 5-H), 3.24 (s, 3H), 3.11 (s, 3H), 2.84 (t, JZ
4.7 Hz, 4H), 1.62–1.52 (m, 6H).
4.1.15. 6-Anilinouracil.10 Pale white solid, mp 326–327 8C
(dec) (lit. 325–327 8C dec); 1H NMR (300 MHz, DMSO-d6)
d 10.46 and 10.17 (2s, 2H, 2NH), 8.25 (s, 1H, NH). 7.29 (d,
JZ5.8 Hz, 1H, 6-H), 7.40–7.12 (m, 5H, Ph), 4.68 (s, 1H,
5-H).
4.1.27. 1,3-Dimethyl-6-(benzylmethylamino)uracil.
Colorless oil; 1H NMR (300 MHz, CDCl3) d 7.41–7.24
(m, 5H, Ph), 5.27 (s, 1H, 5-H), 4.10 (s, 2H), 3.4 7 (s, 3H),
3.34 (s, 3H), 2.60 (s, 3H); 13C NMR (75 MHz, CDCl3)
d163.3, 160.0, 153.3, 135.4, 129.0 (2C), 128.2 (3C), 88.7,
58.1, 39.4, 33.4, 27.9; IR (MeOH): 2924, 2854, 1699, 1655,
1606 cmK1; MS m/e 259 (MC), 244, 137, 91, 69; HRMS
m/e calcd for 259.2989, found 259.1322.
4.1.16. 6-Phenylthiouracil.9 White solid, mp 272–274 8C
(lit. 270–272 8C); H NMR (300 MHz, DMSO-d6) d 11.58
1
and 10.98 (s, 2H, 2NH), 7.65–7.51 (m, 5H, SPh), 4.51 (s,
1H, 5-H).
4.1.17. 6-Phenylselenenyluracil.9 White solid, mp
241–243 8C (lit. 238–240 8C); 1H NMR (300 MHz,
DMSO-d6) d 11.54 and 10.97 (2s, 2H, 2NH), 7.70–7.47
(m, 5H, SePh), 4.68 (s, 1H, 5-H).
Acknowledgements
We thank the financial support of the Chung-Tai Institute of
Health Science Technology and National Science Council.
4.1.18. 1,3-Dimethyl-5-phenylthiouracil.14 White solid,
mp 134–136 8C (lit. 136 8C); H NMR (300 MHz, DMSO-
1
d6) d 8.34 (s, 1H, 6-H), 7.29–7.12 (m, 5H, SPh), 3.35 (s, 3H),
3.18 (s, 3H).
References and notes
1
4.1.19. 1,3-Dimethyl-5-piperidyluracil. Colorless oil; H
NMR (300 MHz, DMSO-d6) d 7.10 (s, 1H, 6-H), 3.27 (s,
3H), 3.14 (s, 3H), 2.76 (t, JZ5.1 Hz, 4H), 1.60–1.45 (m,
6H); 13C NMR (75 MHz, DMSO-d6) d 160.3, 150.2, 130.1,
126.7, 51.1 (2C), 36.2, 27.7, 25.5 (2C), 23.8; IR (MeOH):
2931, 1700, 1650 cmK1; MS m/e 223 (MC), 194, 140, 84,
69; HRMS m/e calcd for 223.2782, found 223.1329.
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needles, mp 131–132 8C (lit. 129–130 8C); 1H NMR
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136–137 8C (lit. 134 8C); 1H NMR (300 MHz, DMSO-d6) d
5.19 (s, 1H, 5-H), 4.12 (q, JZ7.0 Hz, 2H), 3.20 (s, 3H), 3.11
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