2764
S.-R. Sheng et al.
SHORT PAPER
IR (neat): 3128, 2958, 2927, 1616, 1556, 1514, 1459, 1438, 1387,
1365, 1125, 1014, 872, 780 cm–1.
appearing at H = 6.65–6.70 ppm, 8.36–8.40 ppm, respec- 1H NMR: = 8.43 (d, J = 1.6 Hz, 1 H), 7.57 (dd, J = 1.8, 0.8 Hz, 1
ported ratio was based on the integration of the proton sig-
nal on the isoxazole ring in 5a and 5b, 6a and 6b
H), 7.28 (dd, J = 3.5, 0.8 Hz, 1 H), 6.62 (d, J = 1.6 Hz, 1 H), 6.54
(dd, J = 3.5, 1.8 Hz, 1 H).
13C NMR: = 160.9, 146.9, 146.6, 135.0, 128.3, 125.5, 102.2.
EIMS: m/z (%) = 135 (49.2) [M+], 86 (59.7), 84 (100), 78 (52.1), 52
tively. Attempts to improve the yields of them by replac-
ing solvents such as THF and CH2Cl2, changing reaction
temperature or prolonging reaction time were unsuccess-
ful (Table 1, entries 12 and 13).
(53.9), 51 (50.1), 43 (40.8).
In summary, we have developed a mild and efficient
method for the synthesis of 3-substituted isoxazoles by
1,3-dipolar cylcoaddition of phenyl vinyl selenide with ni-
trile oxides and subsequent oxidation-elimination in a
one-pot, two-step transformation.
Anal. Calcd for C7H5NO2: C, 66.22; H, 3.73; N, 10.37. Found: C,
66.16; H, 3.70; N, 10.32.
Acknowledgment
We are grateful for the financial support from the Natural Science
Foundation of Jiangxi Province, P. R. China.
1
Melting points were uncorrected. H NMR (400 MHz) and 13C
NMR (100 MHz) spectra were recorded on a Bruker Avance (400
MHz) spectrometer, using CDCl3 as the solvent and TMS as inter-
nal standard. Mass spectra (EI, 70 eV) were recorded on a HP5989B References
mass spectrometer. IR spectra were recorded on a Bruker Vector 22
(1) (a) Dominguez, E.; Ibeus, E.; Matrinez de Margorta, E.;
spectrometer. Microanalyses were performed with a Carlo-Erba
1106 elemental analyzer. CHCl3 was dried by distillation from P2O5
prior to use. Phenyl vinylic selenides 16 and 27 were prepared ac-
cording to the literature procedures. Aldoximes were synthesized
based on the procedure described in the literature.8 All reactions
were monitored by TLC.
Palacious, J. K.; San Marka, E. J. Org. Chem. 1996, 61,
5435. (b) Buron, C.; Kairon, L. E.; Hslu, A. Tetrahedron
Lett. 1997, 38, 8027. (c) Grunanger, P.; Vitafinzi, P.
Isoxazoles in the Chemistry of Heterocylic Compounds, Vol.
1, Part I; Talyor, E. C., Ed.; Wiley Interscience: New York,
1991, 1–46.
(2) (a) Micetich, R. G. Can. J. Chem. 1970, 48, 467. (b) Wade,
P.; Amin, N. V.; Yen, H.; Price, D. T.; Huhn, G. F. J. Org.
Chem. 1984, 49, 4595. (c) Nunno, L. D.; Scilimati, A.
Tetrahedron 1987, 43, 2181. (d) Cadogan, J. I. G.;
Cameron, D. K.; Gosney, I.; Tinley, E. J.; Wyse, S. J.;
Amaro, A. J. Chem. Soc., Perkin Trans. 1 1991, 2081.
(3) Samuilov, Y. D.; Soloveva, S. E.; Konovalov, A. I.;
Mannafov, T. G. Zh. Org. Khim. 1979, 15, 243.
(4) (a) Kauffmann, T.; Ahlers, H.; Echsler, K.-J.; Schulz, H.;
Tilhard, H.-J. Chem. Ber. 1985, 118, 4496. (b) Pearson, W.
H.; Stevens, E. P. J. Org. Chem. 1998, 63, 9812.
(c) Pearson, W. H.; Szura, D. P.; Postich, M. J. J. Am. Chem.
Soc. 1992, 114, 1329. (d) Pearson, W. H.; Clark, R. B.
Tetrahedron Lett. 1997, 38, 7669.
(5) (a) Reich, H. J. Acc. Chem. Res. 1979, 12, 22. (b) Liotta, D.
Acc. Chem. Res. 1984, 17, 28. (c) Organoselenium
Chemistry; Liotta, D., Ed.; Wiley: New York, 1987.
(d) Back, T. G. The Chemistry of Organic Selenium and
Tellurium Compounds, Vol. 2; Patai, S., Ed.; Wiley:
Chichester, 1987, Chap. 3.
(6) (a) Kataev, E. G.; Mannafov, T. G.; Remizov, A. B.;
Komarovskaya, D. A. J. Org. Chem. (USSR). 1975, 11,
2363. (b) Kataev, E. G.; Mannafov, T. G.; Berdnikov, E. A.;
Komarovskaya, D. A. J. Org. Chem. (USSR). 1973, 9, 1998.
(7) Comasseto, J. V. J. Organomet. Chem. 1983, 253, 131.
(8) Said, S. B.; Skarewski, J.; Mochowski, J. Synth. Commun.
1992, 22, 1851.
(9) Choji, K.; Katsumi, T.; Akira, H. Heterocycles 1994, 37,
1075.
(10) Barber, G. N.; Olofson, R. A. J. Org. Chem. 1978, 43, 3015.
(11) Bast, K.; Christl, M.; Huisgen, R.; Mack, W.; Sustmann, R.
Chem. Ber. 1973, 106, 3258.
Preparation of Isoxazoles; General Procedure
To a stirred solution of N-chlorosuccinimide (NCS, 2.0 mmol) in
anhydrous CHCl3 (5 mL) was added aldoxime (2 mmol) under a N2
atmosphere at r.t. in one portion. Phenyl vinylic selenide 1 or 2 (2
mmol) was added after 20 min, and the Et3N (2.1 mmol in 2 mL of
CHCl3) was added dropwise over ca. 30 min. The mixture was
stirred at r.t. for 12 h, then cooled to 0 °C and 30% H2O2 (0.5 mL)
was added over 10 min. After an additional stirring for 20 min at r.t.,
H2O (5 mL) was added and the CHCl3 layer was separated and
washed with sat. NaHCO3 solution (5 mL). After being dried over
MgSO4, the solution was filtered and the solvent was evaporated in
vacuo. The residue was subjected to silica gel column chromatogra-
phy (10–15% EtOAc in hexane) to give pure product.
Structures of compounds 4a,2c 4b,9 4c,2d 4d,2c 4e,2d 4f,2c 4g,2c 4j,10
4k,10 5,11 612 have been already described, our spectral data were in
accordance with those in the literatures.
3-(p-Fluorophenyl)isoxazole (4h)
The crude product was purified by silica gel column chromatogra-
phy (hexane–EtOAc, 9:1) affording 267 mg (1.64 mmol) of 4h as a
white solid; mp 35–36 °C.
IR (KBr): 3030, 2929, 1607, 1557, 1520, 1494, 1434, 1379, 1236,
1159, 1125, 1098, 885, 842, 777 cm–1.
1H NMR: = 8.38 (d, J = 1.6 Hz, 1 H), 7.77 (d, J = 8.1 Hz, 2 H),
7.12 (d, J = 8.0 Hz, 2 H), 6.66 (d, J = 1.6 Hz, 1 H).
13C NMR: = 166.1, 162.2, 134.1, 128.3, 121.0, 114.7, 102.2.
EIMS: m/z (%) = 163 (100) [M+], 108 (48.3), 107 (61.7), 95 (80.7),
75 (52.1), 57 (49.9), 43 (41.8).
Anal. Calcd for C9H6NFO: C, 66.26; H, 3.71; N, 8.59. Found: C,
66.22; H, 3.65; N, 8.53.
(12) Maeda, M.; Kojima, M. J. Chem. Soc., Perkin Trans. 1 1977,
239.
3-(2-Furyl)isoxazole (4i)
The crude product was purified by silica gel column chromatogra-
phy (hexane–EtOAc, 9:1) affording 222 mg (1.64 mmol) of 4i as
colorless oil.
Synthesis 2003, No. 18, 2763–2764 © Thieme Stuttgart · New York