Synthesis 2015; 47(18): 2791-2798
DOI: 10.1055/s-0034-1378737
special topic
© Georg Thieme Verlag Stuttgart · New York

Synthesis of Isoxazolines and Isoxazoles Inspired by Fipronil

Daniel K. Miller
Department of Chemistry, Ball State University, Muncie, IN 47306-0445, USA   Email: resammelson@bsu.edu
,
Christopher A. Bailey
Department of Chemistry, Ball State University, Muncie, IN 47306-0445, USA   Email: resammelson@bsu.edu
,
Robert E. Sammelson*
Department of Chemistry, Ball State University, Muncie, IN 47306-0445, USA   Email: resammelson@bsu.edu
› Author Affiliations
Further Information

Publication History

Received: 24 April 2015

Accepted after revision: 05 June 2015

Publication Date:
29 July 2015 (eFirst)

Abstract

Phenylpyrazoles (or arylpyrazoles) are known to be extremely potent as noncompetitive inhibitors of the GABA-gated chloride channel on the GABA receptor. This project involves the synthesis of novel isoxazole and isoxazoline heterocycles that have similar structural features to the commercially used phenylpyrazole, fipronil. Synthesis of the appropriately substituted styrenes and phenylacetylenes is followed by 1,3-dipolar cycloaddition reaction with several aliphatic nitrile oxides, which are prepared in situ from aldoximes with bleach. Relative reaction rates were determined for these specialized alkene and alkyne dipolarophiles.

Supporting Information

 
  • References

  • 2 Evans BE, Rittle KE, Bock MG, DiPardo RM, Freidinger RM, Whitter WL, Lundell GF, Veber DF, Anderson PS, Chang RS. L, Lotti VJ, Cerino DJ, Chen TB, Kling PJ, Kunkel KA, Springer JP, Hirshfield J. J. Med. Chem. 1988; 31: 2235
  • 3 Clemett D, Goa KL. Drugs 2000; 59: 957
  • 4 Colliot F, Kukorowski KA, Hawkins DW, Roberts DA In Brighton Crop Protection Conferences–Pests and Diseases . Vol. 1. British Crop Protection Council; Farnham: 1992: 29-34
  • 5 Gant DB, Chalmers AE, Wolff MA, Hoffman HB, Bushey DF. Rev. Toxicol. 1998; 2: 147
  • 6 Chen L, Durkin KA, Casida JE. Proc. Natl. Acd. Sci. U.S.A. 2006; 103: 5185
  • 7 Ormrod D, Wellington K, Wagstaff AJ. Drugs 2002; 62: 2059
    • 8a Aufauvre J, Biron DG, Vidau C, Fontbonne R, Roudel M, Diogon M, Viguès B, Belzunces LP, Delbac F, Blot N. Sci. Rep. 2012; 2: 326
    • 8b Boncristiani H, Underwood R, Schwarz R, Evans JD, Pettis J, Vanengelsdorp D. J. Insect Physiol. 2012; 58: 613
    • 8c Lu C, Warchol KM, Callahan RA. Bull. Insectol. 2014; 67: 125
  • 9 Sammelson RE, Caboni P, Durkin K, Casida JE. Bioorg. Med. Chem. 2004; 12: 3345
    • 10a Alam MS, Kajiki R, Hanatani H, Kong X, Ozoe F, Matsui Y, Matsumura F, Ozoe Y. J. Agric. Food Chem. 2006; 54: 1361
    • 10b Ozoe Y, Yagi K, Nakamura M, Akamatsu M, Miyake T, Matsumura F. Pestic. Biochem. Physiol. 2000; 66: 92
  • 11 Sammelson RE, Miller RB, Kurth MJ. J. Org. Chem. 2000; 65: 2225
  • 12 Sammelson RE, Gurusinghe CD, Kurth JM, Olmstead MM, Kurth MJ. J. Org. Chem. 2002; 67: 876
  • 13 Sammelson RE, Ma T, Galietta LJ. V, Verkman AS, Kurth MJ. Bioorg. Med. Chem. Lett. 2003; 13: 2509
  • 14 Huisgen R In 1,3-Dipolar Cycloaddition Chemistry . Vol. 1. Padwa A. Wiley; New York: 1984: 1-176
  • 15 Tayyari F, Wood DE, Fanwick PE, Sammelson RE. Synthesis 2008; 279
    • 16a Maryanoff BE, Reitz AB. Chem. Rev. 1989; 89: 863
    • 16b Okamoto T, Kobayashi K, Oka S, Tanimoto S. J. Org. Chem. 1988; 53: 4897
  • 17 Brooks LA. J. Am. Chem. Soc. 1944; 66: 1295
    • 18a Doyle MP, Siegfried B, Dellaria JF. Jr. J. Org. Chem. 1977; 42: 2426
    • 18b Krasnokutskaya EA, Semenischeva NI, Filimonov VD, Knochel P. Synthesis 2007; 81
  • 19 Okano K, Tokuyama H, Fukuyama T. J. Am. Chem. Soc. 2006; 128: 7136
  • 20 Wipf P, Weiner WS. 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
  • 22 Bardhan S, Schmitt DC, Porco JA. Org. Lett. 2006; 8: 927
  • 23 Clive D, Angoh AG, Bennett SM. J. Org. Chem. 1987; 52: 1339
  • 24 Kaloko J, Hayford A. Org. Lett. 2005; 7: 4305
  • 25 Jäger V, Colinas PA In Synthetic Applications of 1,3-Dipolar Cycloaddition Chemistry Toward Heterocycles and Natural Products. Padwa A, Pearson WH. Wiley; Hoboken: 2003. Chap. 6
  • 26 Kim JN, Ryu EK. J. Org. Chem. 1992; 57: 1088
  • 27 Kim JN, Ryu EK. J. Org. Chem. 1992; 57: 6649
  • 28 Chen W, Zhang J, Wang B, Zhao Z, Wang X, Hu Y. J. Org. Chem. 2015; 80: 2413
  • 29 Li A, Steinig AG, Kleinberg A, Weng Q, Mulvihill MJ, Wang J, Chen X, Wang T, Dong H, Jin M. US Patent Appl. US 20090197864 A1 20090806, 2009 ; Chem. Abstr. 2009, 950848.
  • 30 Stierli D, Walter H. Patent PCT Int. Appl. WO 2011147690 A1 20111201, 2011 ; Chem. Abstr. 2011, 1544406.
  • 31 Sakai M, Matsumura T, Midorikawa S, Nomoto T, Katsuki R, Muraki T. Patent PCT Int. Appl. WO 2011007839 A1 20110120, 2011 ; Chem. Abstr. 2011, 80024.
  • 32 Vavilala C, Byrne N, Kraml CM, Ho DM, Pascal RA. J. Am. Chem. Soc. 2008; 130: 13549