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D. K. Miller et al.
Special Topic
Synthesis
3-tert-Butyl-5-[2,6-dichloro-4-(trifluoromethyl)phenyl]isoxazole
(13C)
(5) Gant, D. B.; Chalmers, A. E.; Wolff, M. A.; Hoffman, H. B.; Bushey,
D. F. Rev. Toxicol. 1998, 2, 147.
(6) Chen, L.; Durkin, K. A.; Casida, J. E. Proc. Natl. Acd. Sci. U.S.A.
2006, 103, 5185.
2,2-Dimethylpropanal oxime (C; 0.065 g, 0.33 mmol) and 2,6-di-
chloro-4-(trifluoromethyl)phenylacetylene (11; 0.277 g, 2.3 mmol)
gave a light yellow solid; yield: 0.065 g (61%); mp 55–56 °C.
1H NMR (400 MHz, CDCl3): δ = 7.68 (s, 2 H), 6.42 (s, 1 H), 1.42 (s, 9 H).
13C NMR (75 MHz, CDCl3): δ = 172.1, 162.6, 136.7, 133.8 (q, J = 34 Hz),
131.0, 125.3 (q, J = 3.5 Hz), 122.2 (q, J = 270 Hz), 104.5, 32.3, 29.5.
(7) Ormrod, D.; Wellington, K.; Wagstaff, A. J. Drugs 2002, 62, 2059.
(8) (a) Aufauvre, J.; Biron, D. G.; Vidau, C.; Fontbonne, R.; Roudel,
M.; Diogon, M.; Viguès, B.; Belzunces, L. P.; Delbac, F.; Blot, N.
Sci. Rep. 2012, 2, 326. (b) Boncristiani, H.; Underwood, R.;
Schwarz, R.; Evans, J. D.; Pettis, J.; Vanengelsdorp, D. J. Insect
Physiol. 2012, 58, 613. (c) Lu, C.; Warchol, K. M.; Callahan, R. A.
Bull. Insectol. 2014, 67, 125.
Anal. Calcd for C14H12Cl2F3NO: C, 49.73, H, 3.58; N, 4.14. Found: C,
49.65; H, 3.46; N, 3.91.
(9) Sammelson, R. E.; Caboni, P.; Durkin, K.; Casida, J. E. Bioorg. Med.
Chem. 2004, 12, 3345.
5-[2,6-Dichloro-4-(trifluoromethyl)phenyl]-3-(1-ethylpro-
pyl)isoxazole (13D)
(10) (a) Alam, M. S.; Kajiki, R.; Hanatani, H.; Kong, X.; Ozoe, F.;
Matsui, Y.; Matsumura, F.; Ozoe, Y. J. Agric. Food Chem. 2006, 54,
1361. (b) Ozoe, Y.; Yagi, K.; Nakamura, M.; Akamatsu, M.;
Miyake, T.; Matsumura, F. Pestic. Biochem. Physiol. 2000, 66, 92.
(11) Sammelson, R. E.; Miller, R. B.; Kurth, M. J. J. Org. Chem. 2000,
65, 2225.
(12) Sammelson, R. E.; Gurusinghe, C. D.; Kurth, J. M.; Olmstead, M.
M.; Kurth, M. J. J. Org. Chem. 2002, 67, 876.
(13) Sammelson, R. E.; Ma, T.; Galietta, L. J. V.; Verkman, A. S.; Kurth,
M. J. Bioorg. Med. Chem. Lett. 2003, 13, 2509.
2-Ethylbutanal oxime (D; 0.058 g, 0.5 mmol) and 2,6-dichloro-4-(tri-
fluoromethyl)phenylacetylene (11; 0.125 g, 0.52 mmol) gave a yel-
low-orange oil; yield: 0.087 g (50%).
1H NMR (300 MHz, CDCl3): δ = 7.69 (s, 2 H), 6.33 (s, 1 H), 2.82–2.73
(m, 1 H), 1.90–1.49 (m, 4 H), 0.91 (t, J = 7.4 Hz, 6 H).
13C NMR (75 MHz, CDCl3): δ = 167.2, 162.8, 136.8, 133.9 (q, J = 34 Hz),
131.1, 125.3 (q, J = 4.0 Hz), 122.2 (q, J = 271 Hz), 104.6, 40.6, 27.3,
11.7.
(14) Huisgen, R. In 1,3-Dipolar Cycloaddition Chemistry; Vol. 1;
Padwa, A., Ed.; Wiley: New York, 1984, 1–176.
(15) Tayyari, F.; Wood, D. E.; Fanwick, P. E.; Sammelson, R. E. Synthe-
sis 2008, 279.
Anal. Calcd for C15H14Cl2F3NO: C, 51.16; H, 4.01; N, 3.98. Found: C,
51.28; H, 4.12; N, 4.03.
(16) (a) Maryanoff, B. E.; Reitz, A. B. Chem. Rev. 1989, 89, 863.
(b) Okamoto, T.; Kobayashi, K.; Oka, S.; Tanimoto, S. J. Org. Chem.
1988, 53, 4897.
(17) Brooks, L. A. J. Am. Chem. Soc. 1944, 66, 1295.
(18) (a) Doyle, M. P.; Siegfried, B.; Dellaria, J. F. Jr. J. Org. Chem. 1977,
42, 2426. (b) Krasnokutskaya, E. A.; Semenischeva, N. I.;
Filimonov, V. D.; Knochel, P. Synthesis 2007, 81.
(19) Okano, K.; Tokuyama, H.; Fukuyama, T. J. Am. Chem. Soc. 2006,
128, 7136.
(20) Wipf, P.; Weiner, W. S. J. Org. Chem. 1999, 64, 5321.
(21) 4-Isoxazolines are known, but unstable and very reactive.
See:Eicher, T.; Hauptmann, S. The Chemistry of Heterocycles;
Wiley-VCH: Weinheim, 2003, 144–148.
Acknowledgment
We thank Indiana Academy of Science senior research grant for par-
tial support of this research. This work was also supported by funds
from the Lilly Endowment and Ball State University. Amanda Ponsot,
Laura Bandy, Stephanie Pertler, and Ryan Arnett, of this lab, are ac-
knowledged for their thoughtful discussions and suggestions through
related research. Professors John Casida and Mark Kurth are recog-
nized for their inspiration of this work.
Supporting Information
(22) Bardhan, S.; Schmitt, D. C.; Porco, J. A. Org. Lett. 2006, 8, 927.
(23) Clive, D.; Angoh, A. G.; Bennett, S. M. J. Org. Chem. 1987, 52,
1339.
Supporting information for this article is available online at
S
u
p
p
ortioInfgrmoaitn
S
u
p
p
ortiInfogrmoaitn
(24) Kaloko, J.; Hayford, A. Org. Lett. 2005, 7, 4305.
(25) Jäger, V.; Colinas, P. A. In Synthetic Applications of 1,3-Dipolar
Cycloaddition Chemistry Toward Heterocycles and Natural Prod-
ucts; Padwa, A.; Pearson, W. H., Eds.; Wiley: Hoboken, 2003,
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© Georg Thieme Verlag Stuttgart · New York — Synthesis 2015, 47, 2791–2798