separated by column chromatography using chloroform–
methanol as eluent. Similarly the reaction of 6b and 7b
furnished compound 8e and 8f (1:4 ratio from 1H NMR data)
in excellent overall yield.
reaction of 6a and 7b yielded 8c and 8d (1:4 ratio from 1H NMR
data) in a 90% overall yield. The compounds were separated by
column chromatography using chloroform–methanol as eluent.
Similarly the reaction of 6b and 7b furnished compound 8e and
In one of our recent papers12 we reported the attack of a
cyano stabilised carbanion on 6-azido uracils which yielded
1,2,3-triazolo fused tricyclic analogues of uracil via an intra-
molecular cycloaddition of azide to nitriles. There are a few
other reports of the reaction of azidouracils all of which
involve intramolecular cycloaddition of azide to the C5–C6
double bond13 or other transformations14 and sometimes re-
sults in the rupturing of the uracil moiety.15 The present report
is the first example of trapping of an external dipolarophile
by the azide functionality of 6-azidouracils keeping the uracil
moiety intact. Although there was the possibility of the for-
mation of cycloadduct 10 from intramolecular cycloaddition
of the azide at the C5 atom we have not observed the formation
of any such compound under the reaction conditions. More
interestingly neither intramolecular cycloaddition of the
azide to the allylic bond took place to yield compound 9, nor
rupturing of the uracil ring under the reaction conditions.
Further studies on this series of compounds are in progress.
In conclusion we have demonstrated a versatile method for the
synthesis of functionalised complex uracils as novel candidates
in the HEPT series.
8f (1:4 ratio from H NMR data) in excellent overall yield.
1
8a: 1H NMR 90 MHz (CDCl3) 3.00 (s, 3H, >N-Me), 3.40
(d, 2H, -CH2-), 3.60 (s, 3H, -OMe), 3.70 (s, 3H, -OMe), 5.15
(m, 2H, ᎐CH ), 5.70 (s, 1H, C5-H), 5.80 (m, 1H, ᎐CH-). MS
᎐
᎐
2
349 (Mϩ), mp > 250 ЊC. Elemental analysis (%) Calc. C, 48.13,
H, 4.29; N, 20.05. Found: C, 48.10; H, 4.20; N, 20.15. 8b:
1H NMR 90 MHz (CDCl3) 3.10 (s, 3H, >N-Me), 3.15 (s, 3H,
>N-Me), 3.60 (s, 3H, -OMe), 3.70 (s, 3H, -OMe), 5.65 (s, 1H,
C5-H). MS 323 (Mϩ), mp >250 ЊC. Elemental analysis (%)
Calc. C, 44.58; H, 4.02; N, 21.67. Found: C, 44.50; H, 4.00; N,
1
21.65. 8c: H NMR 90 MHz (CDCl3) 3.10 (s, 3H, >N-Me),
3.40 (d, 2H, -CH -), 5.15 (m, 2H, ᎐CH ), 5.60 (s, 1H, C5-H),
᎐
2
5.80 (m, 1H, ᎐CH-), 7.15 (m, 5H, -Ph), 28.30 (s, 1H, ᎐CH-N᎐).
᎐
᎐
᎐
MS 309 (Mϩ), mp >250 ЊC. Elemental analysis (%) Calc. C,
62.13; H, 4.85; N, 22.65. Found: C, 62.15; H, 4.80; N, 22.65.
8d: 1H NMR 90 MHz (CDCl3) 3.10 (s, 3H, >N-Me), 3.40
(d, 2H, -CH -), 5.20 (m, 2H, ᎐CH ), 5.55 (s, 1H, C5-H), 5.75
᎐
(M, 1H, ᎐CH-), 7.15 (m, 5H, -Ph),29.10 (s, 1H, ᎐CH-N<). MS
2
᎐
᎐
309 (Mϩ), mp >250 ЊC. Elemental analysis (%) Calc. C, 62.13;
H, 4.85; N, 22.65. Found: C, 62.15; H, 4.80; N, 22.65. 8e:
1H NMR 90 MHz (CDCl3) 3.10 (s, 3H, >N-Me), 3.15 (s, 3H,
>N-Me), 5.65 (s, 1H, C5-H), 7.15 (m, 5H, -Ph), 8.35 (s, 1H,
᎐CH-N᎐). MS 283 (Mϩ), mp >250 ЊC. Elemental analysis (%)
᎐
᎐
Experimental
Calc. C, 59.36; H, 4.59; N, 24.7. Found: C, 59.30; H, 4.60; N,
24.7. 8f: 1H NMR 90 MHz (CDCl3) 3.10 (s, 3H, >N-Me), 3.15
(s, 3H, >N-Me), 5.60 (s, 1H, C5-H), 7.20 (m, 5H, -Ph), 9.15 (s,
Mps were determined in open capillary tubes on a Buchi
apparatus and are uncorrected. The 90 MHz 1H NMR spectra
were recorded in a JEOL EX 90A spectrometer with CDCl3 as
solvent and tetramethylsilane (TMS) as the internal standard.
The chemical shift values are recorded in δ units (ppm). The IR
spectra were recorded on a Perkin-Elmer 237B IR spectrometer
as KBr discs. Mass spectra were recorded on a INCOS - 50 GC
MS instrument. Elemental analyses were performed on a
Hitachi 026 CHN analyser.
1H, ᎐CH-N<). MS 283 (Mϩ), mp >250 ЊC. Elemental analysis
᎐
(%) Calc. C, 59.36; H, 4.59; N, 24.7. Found: C, 59.30; H, 4.60;
N, 24.7.
CAUTION: All the azides are potentially explosive and should
not be heated as neat solids or liquids. All reactions involving
azides described in this paper were carried out in solution.
References
General procedure for the synthesis of 1-alkyl-6-chlorouracils
5a,b
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and W. D. Ollis, Pergamon Press, Oxford, 1979, vol. 4, p. 493;
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3 T. Miyasaka, H. Tanaka, M. Baba, H. Huyakawa, R.T. Walker,
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To a suspension of 6-chlorouracil 4 (10 mmol) in dichloro-
methane (20 ml) was added tetrabutylammonium bromide
(4 mmol), 10% aqueous NaOH (20 ml) and alkyl bromide
(30 mmol), and the reaction mixture was heated at 40 ЊC.
The progress of the reaction was monitored by TLC, and at
completion, the reaction mixture was cooled and diluted with
water (20 ml). The organic layer was separated and the aqueous
layer extracted with dichloromethane. The organic extract was
washed with 20 ml water and dried over anhydrous sodium
sulfate, and evaporated to obtain compound 5 in 85–90% yield.
1
5a: H NMR 90 MHz (CDCl3) 3.00 (s, 3H), 3.40 (d, 2H), 5.15
(m, 2H), 5.70 (s, 1H), 5.80 (m, 1H). MS 200 (Mϩ), mp 124 ЊC.
5b: (CDCl3) 3.10 (s, 3H), 3.15 (s, 3H), 5.65 (s, 1H). MS 174
(Mϩ), mp 113 ЊC.
6 (a) Y. Ueda, Chemotherapy (Tokyo), 1976, 24, 1661; (b) R. J. Fass
and R. B. Prior, Curr. Ther. Res., 1978, 24, 352.
General procedure for the synthesis of 1-alkyl-6-azidouracil 6a,b
7 U. Saha, A. Das, S. Chakraborty, M. Ghosh and D. K. Roy, J. Inst.
Chem. (India), 1980, 52, 196; (Chem. Abstr., 1981, 44, 139681).
8 (a) P. J. Bhuyan, R. C. Boruah and J. S. Sandhu, J. Org. Chem., 1990,
55, 568; (b) P. J. Bhuyan, J. S. Sandhu and A. C. Ghosh, Tetrahedron
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9 G. Nubel and W. Pfleiderer, Chem. Ber., 1962, 95, 1605.
10 M. Hedayatullah, J. Heterocycl. Chem., 1981, 18, 339.
11 S. Senda, K. Hirota, T. Asao and K. Maruhashi, J. Am. Chem. Soc.,
1978, 100, 7661.
A solution of 6-chlorouracils 5 (5 mmol) and sodium azide
(9 mmol) in ethanol (15 ml) was refluxed for 2 h. Ethanol was
removed by evaporation and the residue was washed with water
and dried. A pale yellow product was obtained in 60% yield.
1
6a: H NMR 90 MHz (CDCl3) 3.00 (s, 3H), 3.40 (d, 2H), 5.15
(m, 2H), 5.70 (s, 1H), 5.80 (m, 1H). MS 207 (Mϩ). IR νmax 2135
cmϪ1. Mp 168 ЊC. 6b: (CDCl3) 3.10 (s, 3H), 3.15 (s, 3H), 5.65
(s, 1H). MS 181 (Mϩ). IR νmax 2135 cmϪ1. Mp 150 ЊC.
12 P. J. Bhuyan, K. C. Lekhok and J. S. Sandhu, J. Chem. Res. (S),
1999, 232.
13 M. Jokic and V. Skaric, J. Chem. Soc., Perkin Trans. 1, 1989, 757.
14 K. Hirota, K. Maruhashi, T. Asao, N. Kitamura, Y. Maki and
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15 T. Sasaki, K. Minamoto, T. Suzuki and S. Yamashita, Tetrahedron,
1980, 36, 865.
General procedure for the reaction of N-alkyl-6-azidouracil with
acetylene
A mixture of 6-azidouracils (0.20 mmol) and acetylenes (0.30
mmol) in toluene (10 ml) were refluxed for 1–2 h. Initially a
clear solution was formed and after a few minutes a thick
precipitate appeared. The reaction mixture was cooled, filtered,
and the solid product washed with toluene and dried. The
Communication 9/06222J
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J. Chem. Soc., Perkin Trans. 1, 1999, 3083–3084