A convenient method for N-1 arylation of uracil derivatives

Article abstract of DOI:10.1016/j.tetlet.2006.04.130

1-(4-Nitrophenyl)- and 1-(2,4-dinitrophenyl)uracil derivatives have been obtained by direct arylation of uracil and its 5-substituted derivatives using 1-fluoro-4-nitrobenzene or 1-fluoro-2,4-dinitrobenzene in the presence of a base. The application of the newly obtained uracil derivatives in further synthesis is also presented.

Full text of DOI:10.1016/j.tetlet.2006.04.130

Tetrahedron Letters 47 (2006) 4653–4657
A convenient method for N-1 arylation of uracil derivatives
Andrzej Gondela and Krzysztof Walczak*
Department of Organic Chemistry, Biochemistry and Biotechnology, Silesian University of Technology,
Krzywoustego 4, 44-100 Gliwice, Poland
Received 27 March 2006; revised 20 April 2006; accepted 26 April 2006
Available online 19 May 2006
Abstract—1-(4-Nitrophenyl)- and 1-(2,4-dinitrophenyl)uracil derivatives have been obtained by direct arylation of uracil and its
5-substituted derivatives using 1-fluoro-4-nitrobenzene or 1-fluoro-2,4-dinitrobenzene in the presence of a base. The application
of the newly obtained uracil derivatives in further synthesis is also presented.
Ó 2006 Elsevier Ltd. All rights reserved.
Many N-substituted uracil derivatives possess biological
activity.1 N-Glycosides of substituted uracils are widely
used in therapy, mainly as antiviral and antineoplastic
agents. The most prominent representatives are 5-fluo-
rouracil and thymine derivatives.2,3 Uramustine, 5-
[N,N0-bis(20-chloroethyl)amino]uracil, is used orally in
the treatment of several leukemias,4 and 5-nitrouracil
derivatives exhibit macrophage growth inhibition.5 1-
Aryl-5-substituted uracils are also useful intermediates
in the synthesis of other uracil derivatives.6–8 It has
been demonstrated that 3-methyl-1-(4-nitrophenyl)-
uracil derivatives possessing an electron-withdrawing
group, such as nitro, cyano, or carbamoyl group, at
the 5-position, when treated with different N-centered
nucleophiles readily undergo ring transformation
according to the ANRORC type reaction.6–8 The 1-(4-
nitrophenyl)-5-substituted uracils were obtained using
known condensation methods. Thus, 3-methyl-5-nitro-
1-(4-nitrophenyl)uracil was obtained by the condensa-
tion of 1-phenylurea with methyl 3,3-dimethoxypropan-
oate and subsequent ring closure under acidic
conditions, followed by N-3 methylation and nitration,
which occurred on both rings (at C-5 of the uracil ring
and C-4 of the benzene ring).9 A similar procedure
was used for the synthesis of 5-cyano-3-methyl-1-(4-
nitrophenyl)uracil.7 In both cases, the final products
were obtained in moderate yields. The other 1-arylura-
cils have been synthesized from substituted ureidoprop-
anoic acids or 1-acryloyl-3-arylureas.10 6-Methyl-1,3-
oxazine-2,4(3H)-dione when treated with an excess of
arylamines was transformed into the appropriate 1-
aryl-6-methyluracils.11 Uracil derivatives, in reaction
with diaryliodonium salts, gave the appropriate N-
mono- and N,N0-diarylation products with high regio-
selectivity.12,13 The reaction of pyridin-2(1H)-one with
triphenylbismuth or tris(3-methoxyphenyl)bismuth gave
the appropriate N-aryl derivatives in moderate yields.14
Attempts at direct N-arylation of uracil derivatives have
also been reported.15,16
As a part of our research interest in the synthetic appli-
cations of 1,5-disubstituted uracil derivatives, the direct
arylation of 5-substituted uracils with activated fluoro-
benzene derivatives under basic conditions was investi-
gated to achieve N-monoarylation with high yields and
regioselectivity. The 5-substituted uracils are weak
NH-acids with pKas in the range of 7.93–9.75, except
for the 5-nitrouracil having a pKa of 5.66.17 In most
cases, potassium carbonate should be a strong enough
base to deprotonate uracils. In a typical procedure, ura-
cils 1a–f were dissolved in DMSO at room temperature,
followed by the addition of a base and a 1-fluorobenzene
derivative (2a or 2b).18 When 1-fluoro-4-nitrobenzene 2a
was used as the arylating agent, the best conversions
were obtained when the reaction was performed at an
elevated temperature (70–80 °C, oil bath) for a period
of 6–48 h. The more reactive 1-fluoro-2,4-dinitro-
benzene reacted at room temperature, and usually after
1–2 h the complete consumption of the starting 2b was
observed (TLC, MeOH–CHCl3, 5:95, v/v). Under these
Keywords: 5-Substituted uracil derivatives; 5-Nitro-1-(4-nitrophenyl)-
uracil; 1-(2,4-Dinitrophenyl)-5-nitrouracil; Nucleophilic aromatic
substitution; ANRORC type reaction.
*
Corresponding author. Tel.: +48 322371792; fax: +48 322372094;
e-mail: krzysztof.walczak@polsl.pl
0040-4039/$ - see front matter Ó 2006 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2006.04.130

4654
A. Gondela, K. Walczak / Tetrahedron Letters 47 (2006) 4653–4657
conditions the formation of only the desired products
was observed. The products 3a–l were isolated as precip-
itates by pouring the reaction mixture onto ice and were
obtained in satisfactory yields (Scheme 1, Table 1).
Crystallization from ethyl acetate or methanol gave
analytically pure compounds.18 Additional products
(approx 10%) could be isolated from post-crystallization
liquors using column chromatography.
of the reaction mixture indicated the presence of unre-
acted substrates and traces of 4-nitrophenol. 1-(4-Nitro-
phenyl)-5-nitrouracil 4a was obtained by nitration of 3a
using a nitrating mixture (fuming nitric acid and sulfuric
acid (98%) in the volume ratio 1:2) at 0 °C in 86% yield
(Scheme 2). The position of uracil arylation was
confirmed by the conversion of 3a into the known
3-methyl-5-nitro-1-(4-nitrophenyl)uracil20 6a by methyl-
ation at N-3, followed by nitration at C-5 of the uracil
ring. The same procedure was applied for the conversion
of 3b into 6b. The structures of all the compounds ob-
tained were confirmed on the basis of elemental analysis
and NMR spectroscopy (Table 2). It should be men-
tioned that the formation of neither N-3 nor O-arylation
products was detected. In the case of uracil and thymine
arylations, inspection of TLC plates indicated the pres-
ence of a by-product. We separated these substances in
The arylation of unsubstituted uracil 1a using 1-fluoro-
2,4-dinitrobenzene has been performed in the presence
of triethylamine as a base.19 However, in the presence
of potassium carbonate the formation of a bisarylation
product was observed.
In the case of 5-nitrouracil, the anion of which is less
nucleophilic, the direct arylation failed. Examination
O
1
a
b
c
d
e
f
3
a, b
R
H
R
F
HN
O
c, d Me
e, f
g, h Cl
i, j
k
R'
R
O
N
HN
i or ii, or iii
F
+
R'
O
N
H
Br
CN
NO2
1a-f
2a,b
NO2
g
l
NO2
N
3a-i
N
Me
Scheme 1. 2a: R0 = H, 2b: R0 = NO2. Reagents and conditions: (i) R = H, Me, F, Cl, Br, (1) DMSO, K2CO3, 80 °C, 0.5 h, (2) 2a, 6–48 h; (ii) R = H,
Me, (1) DMSO, Et3N, 50 °C, 15 min, (2) 2b, 25 °C, 1 h; (iii) R = F, Cl, Br, (1) DMSO, K2CO3, 25 °C, ca. 10 min, (2) 2b, 1–2 h.
Table 1. Yields and properties of 1,5-disubstituted uracil derivatives
Entry
Product
R
R0
Yield (%)
Mp (°C)
1
2
3
4
5
6
7
8
9
3a
3b
3c
3d
3e
3f
H
H
CH3
CH3
F
F
Cl
Cl
H
NO2
H
NO2
H
NO2
H
NO2
H
NO2
NO2
NO2
87
62
51
66
70
68
74
69
60
52
93
50
306–308
221–222
283–284
276–277
244–245
248–249
257–258
243–244
269–270
270–271
260–261
300–302
3g
3h
3i
Br
Br
CN
10
11
12
3j
3k
3l
2-Methyl-4-nitroimidazol-1-yl
O
O
O
N
O
NO2
Me
O
Me
N
NO2
R
HN
HN
N
O
N
O
N
O
N
ii
i
i
R
R
R
NO2
NO2
NO2
NO2
5a,b
6a,b
3a,b
4a,b
Scheme 2. a: R = H, b: R = NO2. Reagents and conditions: (i) concd HNO3, concd H2SO4, (1) 0 °C, 30 min, (2) 25 °C, 4 h; (ii) (1) DMF, NaH,
30 min, (2) CH3I, 20 °C, 2.5 h.

Table 2. 1H NMR and 13C NMR dataa for compounds 3a–l
Compound
1H NMR (300 MHz)
13C NMR (75 MHz)
3a
5.77 (d, 1H, J = 7.9 Hz, H-5), 7.75 (d, 2H, J = 8.9 Hz, Ar), 7.81 (d, 1H, J = 7.9 Hz, H-6),
8.34 (d, 2H, J = 8.9 Hz, Ar), 11.55 (br s, 1H, NH)
102.55, 124.28 (2C), 127.97 (2C), 144.11, 144.44, 146.46, 150.00, 163.52
3b
3c
3d
3e
5.89 (d, 1H, J = 8.0 Hz, H-5), 7.92 (d, 1H, J = 8.0 Hz, H-6), 8.03 (d, 1H, J = 8.7 Hz, H-60),
8.73 (dd, 1H, J = 2.6, 8.7 Hz, H-50), 8.85 (d, 1H, J = 2.6 Hz, H-30), 11.78 (br s, 1H, NH)
1.84 (d, 3H, J = 0.9 Hz, CH3), 7.72 (d, 1H, J = 0.9 Hz, H-6), 7.75 (d, 2H, J = 9.0 Hz, Ar),
8.33 (d, 2H, J = 9.0 Hz, Ar), 11.60 (1H, NH)
103.14, 120.71, 129.21, 131.50, 136.09, 143.69, 145.08, 146.97, 149.59, 163.25
11.89 (CH3), 110.33, 124.26 (2C), 127.82 (2C), 140.01, 144.27, 146.23,
149.93, 164.14
1.87 (s, 3H, CH3), 7.85 (s, 1H, H-6), 8.02 (d, 1H, J = 8.7 Hz, H-60), 8.71 (dd, 1H, J = 2.7,
8.7 Hz, H-50), 8.83 (d, 1H, J = 2.7 Hz, H-30), 11.80 (s, 1H, NH)
11.96 (CH3), 111.06, 120.71, 129.15, 131.22, 136.21, 139.20, 145.05, 146.73,
149.54, 163.99
3
2
7.76 (d, 2H, J = 9.3 Hz, Ar), 8.32 (d, 1H, JH–F = 6.9 Hz, H-6), 8.34 (d, 2H, 9.3 Hz, Ar),
124.25 (2C), 128.10 (2C), 129.35 (d, JC–F = 36 Hz, C-6), 140.70 (d,
12.09 (s, 1H, NH)
1JC–F = 232 Hz, C-5), 143.72, 146.47, 148.76 (C-2), 157.45
2
(d, JC–F = 26 Hz, C-4)
3
2
3f
8.04 (d, 1H, J = 8.7 Hz, H-60), 8.49 (d, 1H, JH–F = 6.6 Hz, H-6), 8.75 (dd, 1H, J = 2.7,
120.80, 128.72 (d, JC–F = 35 Hz, C-6), 129.24, 131.70, 135.53, 140.8
1
8.7 Hz, H-50), 8.86 (d, 1H, J = 2.7 Hz, H-30), 12.36 (s, 1H, NH)
(d, JC–F = 233 Hz, H-5), 145.17, 147.06, 148.40 (C-2), 157.29
2
(d, JC–F = 26 Hz, C-4)
3g
3h
7.77 (d, 2H, J = 6.9 Hz, Ar), 8.32 (s, 1H, H-6), 8.34 (d, 2H, J = 6.9 Hz, Ar), 12.09 (s, 1H, NH)
8.08 (d, 1H, J = 8.7 Hz, H-60), 8.50 (s, 1H, H-6), 8.74 (dd, 1H, J = 2.7, 8.7 Hz, H-50), 8.87
(d, 1H, J = 2.7 Hz, H-30), 12.36 (s, 1H, NH)
108.16, 124.24 (2C), 128.33 (2C), 141.75, 143.52, 146.70, 149.28, 159.45
108.83, 120.78, 129.29, 131.96, 135.41, 140.95, 144.98, 147.23, 148.91, 159.22
3i
3j
7.78 (d, 2H, J = 9.0 Hz, Ar), 8.34 (d, 2H, J = 9.0 Hz, Ar), 8.36 (s, 1H, H-6), 12.05 (s, 1H, NH)
8.08 (d, 1H, J = 8.7 Hz, H-60), 8.54 (s, 1H, H-6), 8.75 (dd, 1H, J = 2.4, 8.7 Hz, H-50), 8.76 (d,
1H, J = 2.4 Hz, H-30), 12.31 (s, 1H, NH)
96.83, 124.21 (2C), 128.32 (2C), 143.48, 143.90, 146.69, 149.48, 159.59
97.38, 120.73, 129.25, 131,98, 135.39, 143.10, 144.90, 147.20, 149.12, 159.38
3k
8.10 (d, 1H, J = 9.0 Hz, H-60), 8.81(dd, 1H, J = 2.7, 9.0 Hz, H-50), 8.91 (d, 1H, J = 2.7 Hz,
H-30), 9.03 (s, 1H, H-6), 12.59 (s, 1H, NH)
89.97 (CN), 113.50, 120.96, 129.61, 132.09, 134.79, 144.77, 147.75, 148.44,
153.15, 160.02
13.11 (CH3), 113.96, 121.62, 123.78, 129.95, 132.49, 136.56, 143.72, 146.21,
146.92, 147.32, 148.50, 149.75, 160.23
3lb
2.40 (s, 3H, CH3 imidazoyl), 8.23 (d, 1H, J = 8.7 Hz, H-60), 8.25 (s, 1H, H-5imidazoyl), 8.73
(s, 1H, H-6), 8.83 (dd, 1H, J = 2.4, 8.7 Hz, H-50), 8.97 (d, 1H, J = 2.4 Hz, H-30),
12.34 (s, 1H, NH)
a Chemical shift (d) in ppm, DMSO-d6 as a solvent.
b Acetone-d6.

4656
A. Gondela, K. Walczak / Tetrahedron Letters 47 (2006) 4653–4657
O
N
NO2
NO2
O
N
HN
NH2
NO2
R
HN
NH2
R
O2N
O
R'
+
+
DMF, 25 oC,
24 hr.
O
NO2
7a-c
R'
8a-c
NO2
7, 8
R
OH
H
R'
CH3
CH2OH
OH
9
a
b
c
4b
H
Scheme 3.
amounts not exceeding 2% (as calculated based on start-
ing 1a and 1b) and on the basis of NMR spectra we
assigned the structures as 1,3-diarylation products.
with the US National Institute of Allergy and Infectious
Diseases.
It has been demonstrated that 3-methyl-5-nitro-1-(4-
nitrophenyl)uracil 6a when treated with primary amines
undergoes ring transformation according to the AN-
RORC mechanism.6 1-(2,4-Dinitrophenyl)-5-nitrouracil
4b possessing an additional nitro group on the benzene
ring should be a more efficient nucleofuge in the AN-
RORC type reaction. In initial trials, 4b was subjected
to reaction with amino alcohols 7a–c (Scheme 3), in
anhydrous DMF at room temperature. The desired
products 8a–c were obtained in satisfactory yields after
purification by column chromatography.21 The 2,4-
dinitroaniline 9, a side product formed in this reaction,
was isolated and identified by comparison with an
References and notes
1. Block, J. H.; Beale, J. M. In Organic Medicinal and
Pharmaceutical Chemistry, 11th ed.; Lippincott Williams
& Wilkins: London, 2004; pp 375–382, 406–414.
2. Longley, D. B.; Harkin, D. P.; Johnston, P. G. Nat. Rev.
2003, 3, 330–338.
3. Hoffmann, Ch.; Rockstroh, J. K.; Kamps, B. S. HIV
Medicine 2005; Flying Publisher; Steinhauser: Paris, 2005;
pp 620–683.
4. Baraldi, P. G.; Romagnoli, R.; Guadix, A. E.; Pineda de
las Infantas, M. J. P.; Gallo, M. A.; Espinosa, A.;
Martinez, A.; Bingham, J. P.; Hartley, J. A. J. Med.
Chem. 2002, 45, 3630–3638.
1
authentic sample (mp and H NMR).22
´
5. Copik, A.; Suwinski, J.; Walczak, K.; Bronikowska, J.;
´
Czuba, Z.; Krol, W. Nucleosides, Nucleotides Nucleic
Acids Res. 2002, 21, 377–383.
6. Gondela, A.; Walczak, K. Tetrahedron Lett. 2003, 44,
7291–7293.
All newly synthesized compounds were subjected to pri-
mary bioactivity assays as inhibitors against Mycobacte-
rium tuberculosis; compound 4b exhibited an inhibition
ability of 93%.
´
7. Gondela, A.; Gabanski, R.; Walczak, K. Tetrahedron
Lett. 2004, 45, 8007–8009.
8. Gondela, A.; Walczak, K. Tetrahedron: Asymmetry 2005,
16, 2107–2112.
9. Winckelmann, I.; Larsen, E. H. Synthesis 1986, 12, 1041–
1044.
10. Gabel, N. W.; Binkley, S. B. J. Org. Chem. 1958, 23, 643–
645.
11. Singh, H.; Singh, P.; Aggarwal, P.; Kumar, S. J. Chem.
Soc., Perkin Trans. 1 1993, 731–735.
In conclusion, an effective method for the introduction
of 4-nitrophenyl and 2,4-dinitrophenyl groups on the
N-1 nitrogen atom of uracil is described. The conditions
applied provided products with high regioselectivity in
good yields. The hitherto unknown 1-(2,4-dinitrophen-
yl)-5-nitrouracil can be used as a substrate in nucleo-
philic substitution reactions of the ANRORC type.
This is the first example when a 5-nitrouracil derivative
unsubstituted at N-3 has been used as substrate in an
ANRORC type reaction. The results obtained with
derivative 4b have encouraged us to prepare other nitro-
uracil derivatives, the synthesis of which will be pub-
lished in due time.
12. Maruyama, T.; Fujiwara, K.; Fukuhara, M. J. Chem.
Soc., Perkin Trans. 1 1995, 733–734.
13. Jacobsen, S. A.; Rødbotten, S.; Benneche, T. J. Chem.
Soc., Perkin Trans. 1 1999, 3265–3268.
´
14. Meigh, J. P.; Alvarez, M.; Joule, J. A. J. Chem. Soc.,
Perkin Trans. 1 2001, 2012–2021.
15. Zhou, T.; Li, T.-C.; Chen, Z.-C. Helv. Chim. Acta 2005,
88, 290–296.
16. Boga, C.; Bonmartini, A. C.; Fornali, L.; Modarelli, V.;
Righi, L.; Sgarabotto, P. J. Chem. Res. (M) 2001, 12,
1217.
Acknowledgements
17. Jang, Y. H.; Sowers, L. C.; Cagin, T.; Goddard, W. A. J.
Phys. Chem. A 2001, 105, 274–280.
This work was supported by a Grant from the Ministry
of Education and Science (No. 3 T09A 079 29). Antimy-
cobacterial data were provided by the Tuberculosis
Antimicrobial Acquisition and Coordinating Facility
(TAACF) at the Southern Research Institute in
Alabama through a research and development contract
18. Synthesis of 1-(4-nitrophenyl)- or 1-(2,4-dinitrophenyl)-5-
substituted uracil derivatives 3 (general procedure): To a
solution of 5-substituted uracil (2.1 mmol) in anhydrous
DMSO (6 ml), potassium carbonate was added (1 mmol).
After 10 min, 2a or 2b (2 mmol) was added in one portion.

A. Gondela, K. Walczak / Tetrahedron Letters 47 (2006) 4653–4657
4657
The resulting yellow-red solution was stirred until the
substrate had been consumed and was then poured into
ice–water (25 g/25 ml). The precipitate formed was filtered
off and after drying in air was crystallized from methanol
or ethyl acetate–methanol (1:3).
1-(4-Nitrophenyl)uracil 3a: Anal. Calcd for C10H7N3O4
(233.18): C, 51.51; H, 3.03; N, 18.02. Found: C, 51.39; H,
2.97; N, 17.89.
21. Synthesis of 5-nitro-1-substituted uracils 8a–c from 1-(2,4-
dinitrophenyl)-5-nitrouracil (general procedure): To a
solution of amino alcohol (1.5 mmol) dissolved in DMF
(5 ml), 1-(2,4-dinitrophenyl)-5-nitrouracil (1.0 mmol) was
added at room temperature while stirring. After consump-
tion of the starting material (24 h, TLC MeOH–CHCl3,
20:80), the solvent was evaporated under reduced pressure
and the oily residue was purified on a silica gel column
using a mixture of MeOH and CHCl3 in a ratio of 10:90.
The isolated product was crystallized from aqueous
methanol (30% H2O v/v).
5-Chloro-1-(2,4-dinitrophenyl)uracil 3h: Anal. Calcd for
C10H5ClN4O6 (312.63): C, 38.42; H, 1.61; N, 17.92.
Found: C, 38.45; H, 1.35; N, 17.93.
1-(2,4-Dinitrophenyl)-5-nitrouracil 4b: To a suspension of
3b (2.13 g, 7.67 mmol) in concentrated sulfuric acid
(d = 1.83 g/ml, 7.0 ml) cooled in an ice bath to 0 °C,
fuming nitric acid (d = 1.5 g/ml, 3.5 ml) was added drop-
wise at a temperature below 5 °C while stirring. After the
addition of nitric acid, the ice bath was removed and
stirring was continued for 4 h at room temperature. Then,
the reaction mixture was poured into ice–water (200 g,
1:1). The precipitated product was filtered off, rinsed with
cold water to pH neutral and then with cold methanol
Compound 8a: ( )-1-(2-Hydroxypropyl)-5-nitrouracil:
1
Yield 0.18 g (85%); mp 233–234 °C; H NMR (300 MHz,
DMSO-d6): d (ppm) 1.09 (d, 3H, J = 6.3 Hz, H-30), 3.35
(dd, 1H, J = 8.7, 12.9 Hz, H-10 ), 3.80–3.92 (m, 1H, H-20),
a
3.95 (dd, 1H, J = 2.7, 12.9 Hz, H-10 ), 4.58 (d, 1H,
b
J = 4.5 Hz, OH), 9.07 (s, 1H, H-6), 12.02 (br s, 1H,
NH). 13C NMR (75 MHz, DMSO-d6): d (ppm) 20.56,
55.63, 63.51, 124.37, 149.39, 151.39, 155.04. Anal. Calcd
for C7H9N3O5 (215.17): C, 39.08; H, 4.22; N, 19.53.
Found: C, 39.10; H, 4.36; N, 19.15.
Compound 8b: 1-(3-Hydroxypropyl)-5-nitrouracil: Yield
0.11 g (52%), mp 185–187 °C; 1H NMR (300 MHz,
DMSO-d6): d (ppm) 1.79 (p, 2H, J = 6.5 Hz, H-20), 3.47
(dt, 2H, J = 5.1, 5.7 Hz, H-30), 3.92 (t, 2H, J = 6.5 Hz, H-
10), 4.58 (t, 1H, J = 5.1 Hz, OH), 9.20 (s, 1H, H-6), 11.98
(br s, 1H, NH). 13C NMR (75 MHz, DMSO-d6): d (ppm)
30.94, 47.28, 57.81, 124.66, 149.29, 150.97, 155.00. Anal.
Calcd for C7H9N3O5 (215.17): C, 39.08; H, 4.22; N, 19.53.
Found: C, 39.08; H, 4.26; N, 19.26.
1
(5 ml). Yield 2.03 g (84%), mp 267–269 °C (decomp.); H
NMR (300 MHz, DMSO-d6): d (ppm) 8.16 (d, 1H,
J = 8.4 Hz, H-60), 8.81 (dd, 1H, J = 2.4, 8.4 Hz, H-50),
8.95 (d, 1H, J = 2.4 Hz, H-30), 9.50 (s, 1H, H-6), 12.63 (br
s, 1H, NH). 13C NMR (75 MHz, DMSO-d6): d (ppm)
120.88, 126.71, 129.65, 132.60, 134.72, 144.90, 147.92,
148.24, 148.66, 154.73. Anal. Calcd for C10H5N5O8
(323.18): C, 37.17; H, 1.56; N, 21.67. Found: C, 37.31;
H, 1.72; N, 21.69.
19. Synthesis of 1-(2,4-dinitrophenyl)uracil 3b: Uracil 1a
(10 mmol) was dissolved in DMSO (10 ml) at 50 °C,
triethylamine was added dropwise while stirring and the
temperature was cooled to rt. To this solution, 1-fluoro-
2,4-dinitrobenzene (1.8 g, 9.7 mmol) in DMSO (1 ml) was
added. The reaction mixture was stirred for 30 min and
poured onto crushed ice (100 g). The precipitate was
filtered off, washed with water and dried. The crude
product (2.25 g) was crystallized from glacial acetic acid.
Anal. Calcd for C10H6N4O6 (278.18): C, 43.18; H, 2.17; N,
20.14. Found: C, 42.96; H, 2.21; N, 19.89.
Compound 8c: 1-(2-Hydroxyethyl)-5-nitrouracil: Yield
0.1 g (50%), mp 239–241 °C; 1H NMR (300 MHz,
DMSO-d6): d (ppm) 3.61 (t, 2H, J = 4.9 Hz, H-20), 4.92
(t, 2H, J = 4.9 Hz, H-10), 5.02 (br s, 1H, OH), 9.12 (s, 1H,
H-6), 12.03 (br s, 1H, NH). 13C NMR (75 MHz, DMSO-
d6): d (ppm) 51.42, 58.04, 124.44, 149.32, 151.36, 155.11.
Anal. Calcd for C6H7N3O5 (201.14): C, 35.83; H, 3.51; N,
20.89. Found: C, 35.91; H, 3.62; N, 20.47.
22. 2,4-Dinitroaniline 9; mp 177–179 °C (mp of authentic
sample 176–178 °C). 1H NMR (300 MHz, CDCl3): d
(ppm) 7.12 (d, 1H, J = 9.0 Hz, H-6), 8.01 (br s, 2H,
NH2), 8.11 (dd, 1H J = 2.7, 9.0 Hz, H-5), 9.00 (d, 1H,
J = 2.7 Hz, H-3).
20. Hirota, K.; Kitade, Y.; Sajki, H.; Maki, Y. J. Chem. Soc.,
Perkin Trans. 1 1990, 367–373.