E. Leyva et al. / Tetrahedron Letters 51 (2010) 3978–3979
3979
Scheme 1.
Scheme 2.
hydrogen bonding (between the neighboring amino and nitro
groups) enforced high degree of coplanarity between the nitro
7. Ghosh, P. B.; Everitt, B. J. J. Med. Chem. 1974, 17, 203.
8
9
.
.
Ghosh, P. B.; Ternai, B.; Whitehouse, M. W. Med. Res. Rev. 1981, 2, 158.
Ghosh, P. B.; Whitehouse, M. W. J. Med. Chem. 1969, 12, 505.
group and the benzene ring, thus facilitating N
Scheme 1).
The pyridofuroxans 3a–c described here were isolated as single
2
elimination
1
1
1
0. Porter, A. E. A. Comprehensive Heterocyclic Chemistry; Pergamon Press: New
York, 1984. p 157.
1. Zarranz, B.; Jaso, A.; Aldana, I.; Monge, A.; Maurel, S.; Dcharo, E.; Julian, V.;
Sauvain, M. Arzneim.-Forsch. 2005, 55, 754.
2. Aguirre, G.; Boiani, L.; Boiani, M.; Cerecetto, H.; Di Maio, R.; González, M.;
Porcal, W.; Denicola, A.; Piro, E.; Castellano, E.; Sant’Anna, C. M.; Barreiro, E.
Bioorg. Med. Chem. 2005, 13, 6336.
(
crystalline products. There was no evidence for the existence of
more than one isomer. In a previous study, a valence tautomeriza-
3
1
tion has been proposed for these type of compounds (Scheme 2).
1
1
3. Jaso, A.; Zarranz, B.; Aldana, I.; Monge, A. J. Med. Chem. 2005, 48, 2019.
4. Boyer, J. H.; Elzey, S. E., Jr. J. Org. Chem. 1961, 26, 4684.
The rearrangement involves oxygen migration between N1 and N3
and the isomerization occurs via an o-dinitrosopyridine intermedi-
ate. NMR analysis of the compounds prepared 3a–c indicated the
N1-oxide as the only isomer present. In fact, it has been reported
that this isomer is favored in a pyridofuroxan crystalline solid at
15. Gaughran, R. J.; Picard, J. P.; Kaufman, J. V. R. J. Am. Chem. Soc. 1954, 76, 2233.
16. Boulton, A. J.; Gripper Gray, A. C.; Katritzki, A. R. J. Chem. Soc. 1965, 5958.
17. Leyva, S.; Castanedo, V.; Leyva, E. J. Fluorine Chem. 2003, 121, 171.
18. Kotovskaya, S. K.; Romanova, S. A.; Charushin, V. N.; Kodess, M. I.; Chupakhin,
O. N. J. Fluorine Chem. 2004, 125, 421.
3
1
1
2
2
9. Ayyangar, N. R.; Madan Kumar, S.; Srinivasan, Z. V. Synthesis 1987, 616.
0. Dyall, L. K. Aust. J. Chem. 1984, 37, 2013.
1. Dicskson, N. J.; Dyall, L. K. Aust. J. Chem. 1980, 33, 91.
ambient temperature. It has been demonstrated that the N1-
oxide isomer is favored due to electronic repulsion between the
5
lone pairs of oxygen (N–O) and nitrogen in the pyridine ring. Fur-
22. Dyall, L. K. Aust. J. Chem. 1986, 39, 89.
23. Rauhut, G.; Eckert, F. J. Phys. Chem. A 1999, 103, 9086.
thermore, steric and electronic effects due to nitrogen on pyridofu-
roxans have been previously studied.5 Energetically favorable
24.
Dyall, L. K. Aust. J. Chem. 1975, 28, 2147.
25. McCulla, R. D.; Burdzinski, G.; Platz, M. S. Org. Lett. 2006, 8, 1637.
charge delocalization can also contribute to the position of this
26. Rauhut, G.; Jarzecki, A. A.; Pulay, P. J. Comput. Chem. 1997, 18(4), 489.
5
1
equilibrium.
27. 4-Pyridofuroxan, 3a. Yellow solid; yield 40%; mp 182 °C. H NMR (MeOD, ppm):
8.52 (1H, dd, aromatic
H
ortho
,
J
ortho = 7.81 Hz,
J
meta = 1.95 Hz), 6.50 (1H, t,
In conclusion, 2-azido-3-nitropyridines 2a–c decompose spon-
taneously to give the corresponding pyridofuroxans 3a–c. There-
fore, the pyridine ring must facilitate the cyclic transition state
for the concerted one-step mechanism.
À1
aromatic Hmeta, Jortho = 6.52 Hz), 7.82 (1H, dd, aromatic Hpara). IR (cm ): 3109
(
C–H), 1650 and 1590 (two peaks, exocyclic NO bond), 1550–1500 (two peaks,
C@C and C@N), 1080 (endocyclic NO bond), 850 (weak peak, N–O furoxan).
Exact mass for C : 137.0225 amu, observed: 137.0220 amu.
8. 7-Methyl-4-pyridofuroxan, 3b. Pale brown solid; yield 60%; mp 212–214 °C. 1H
5 3 3 2
H N O
2
NMR (MeOD, ppm): 2.17 (3H, s, CH
3
), 7.38 (1H, d, aromatic
H
ortho
,
À1
Acknowledgments
Jortho = 6.64 Hz), 6.25 (1H, d, aromatic Hmeta). IR (cm ): 3104 and 2983 (C–
H), 1660–1610 (two peaks, exocyclic NO bond), 1520–1500 (two peaks, C@C
and C@N), 1100 (endocyclic NO bond), 855 (weak peak, N–O furoxan). Exact
We would like to acknowledge financial support by CONACYT
mass for C
6 5 3 2
H N O : 151.0381 amu, observed: 151.0380 amu.
29. 6-Bromo-4-pyridofuroxan, 3c. Yellow solid; yield 73%; mp 208–210 °C. 1H NMR
(
Grant 45936-Q) and UASLP (Grant C08-FRC-02-17.17). We would
(
MeOD, ppm): 8.40 (1H, d, aromatic
H
ortho
,
J
meta = 2.73 Hz), 7.85 (1H, d,
like to thank Professor Alan Weedon from University of Western
Ontario for help with NMR and MS measurements.
À1
aromatic Hpara). IR (cm ): 3056 (C–H), 1720 and 1650 (two peaks, exocyclic
NO bond), 1570–1520 (two peaks, C@C and C@N), 1204 (C–Br), 1080
(
C
endocyclic NO bond), 840 (weak peak, N–O furoxan). Exact mass for
BrN : 151.0381 amu, observed: 151.0380 amu.
References and notes
5
H
2
3 2
O
3
3
0. Chaykovsky, M.; Adolph, H. G. J. Heterocycl. Chem. 1991, 28, 1491.
1. Cmoch, P.; Kamienski, B.; Kamienska-Trela, K.; Stefaniak, L.; Webb, G. A. J. Phys.
Org. Chem. 2000, 13, 480.
2. Experimental procedure: the corresponding 2-amino-3-nitropyridine (6 mmol)
derivative 1 was dissolved in 5 mL of trifluoroacetic acid. The solution was
cooled to 15 °C and kept at this temperature throughout the reactions. An
aqueous solution (2 M) of sodium nitrite was slowly added (32 mmol). The
reaction mixture was stirred for 30 min. An aqueous solution of sodium azide
1.
2.
3.
Davis, K. L.; Martin, E.; Turko, I. V.; Murad, F. Annu. Rev. Pharmacol. Toxicol.
001, 41, 203, and references cited therein.
Napoli, C.; Ignarro, L. J. Annu. Rev. Pharmacol. Toxicol. 2003, 43, 97, and
references cited therein.
2
3
Wang, P. G.; Xian, M.; Tang, X.; Wu, X.; Wen, Z.; Cai, T.; Janczuk, A. J. Chem. Rev.
2
002, 102, 1091, and references cited therein.
4
5
.
.
Sliwa, W.; Thomas, A. Heterocycles 1985, 23, 997.
Katrizky, A. R.; Gordeev, M. F. Heterocycles 1993, 35, 483, and references
therein.
(
32 mmol, 2 M) was added dropwise. The resulting mixture was allowed to
warm to room temperature for one more hour. The white precipitate produced
was filtered, washed with water, and dried to give the corresponding
pyridofuroxan 3.
6
.
Gasco, A.; Boulton, A. J. Adv. Heterocycl. Chem. 1981, 29, 251.