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Synlett 2008(2): 217-220  
DOI: 10.1055/s-2007-1000871
LETTER
© Georg Thieme Verlag Stuttgart · New York

Iodoarene-Mediated One-Pot Preparation of 2,4,5-Trisubstituted Oxazoles from Ketones

Yuhta Kawano, Hideo Togo*
Graduate School of Science, Chiba University, Yayoi-cho 1-33, Inage-ku Chiba 263-8522, Japan
e-Mail: togo@faculty.chiba-u.jp;
Further Information

Publication History

Received 24 October 2007
Publication Date:
21 December 2007 (online)

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Abstract

2-Methyl-5-aryloxazole and 2-ethyl-5-aryloxazole derivatives were smoothly and efficiently obtained in one-pot manner from alkyl aryl ketones with iodoarene, m-chloroperbenzoic acid, and trifluoromethanesulfonic acid in acetonitrile and propionitrile, respectively. In these reactions, iodoarene works as a catalyst.

Key words

2,4,5-trisubstituted oxazoles - one-pot reaction - MCPBA - iodoarene

    References and Notes

  • 1a Comprehensive Heterocyclic Chemistry   Vol. 6:  Boyd GV. Katritzky AR. Rees CW. Pergamon; Oxford: 1984.  Chap. 4.18.
    CrossrefGoogle Scholar
  • 1b Comprehensive Heterocyclic Chemistry II   Vol. 3:  Hartner FWJr. Katritzky AR. Rees CW. Scriven EFV. Elsevier Science; Oxford: 1996.  Chap. 3.04.
    CrossrefGoogle Scholar
  • 1c Pattenden G. J. Heterocycl. Chem.  1992,  29:  607 
    CrossrefGoogle Scholar
  • 1d Michael JP. Pattenden G. Angew. Chem., Int. Ed. Engl.  1993,  32:  1 
    CrossrefGoogle Scholar
  • 1e Wipf P. Chem. Rev.  1995,  95:  2115 
    CrossrefGoogle Scholar
  • 1f Vedejs E. Monahan SD. J. Org. Chem.  1996,  61:  5192 
    CrossrefGoogle Scholar
  • 2 Nagayoshi K. Sato T. Chem. Lett.  1983,  12:  1355 
    Google Scholar
  • 3 Lee JC. Hong T. Tetrahedron Lett.  1997,  38:  8959 
    CrossrefGoogle Scholar
  • 4 Varma RS. Kumar D. J. Heterocycl. Chem.  1998,  35:  1533 
    CrossrefGoogle Scholar
  • 5 Lee JC. Choi HJ. Lee YC. Tetrahedron Lett.  2003,  44:  123 
    CrossrefGoogle Scholar
  • 6 Ochiai M. Takeuchi Y. Katayama T. Sueda T. Miyamoto K. J. Am. Chem. Soc.  2005,  127:  12244 
    CrossrefPubMedGoogle Scholar
  • 7 Dohi T. Maruyama A. Yoshimura M. Morimoto K. Tohma H. Kita Y. Angew. Chem. Int. Ed.  2005,  44:  6193 
    CrossrefPubMedGoogle Scholar
  • 8 Yamamoto Y. Togo H. Synlett  2005,  2486 
    Article in Thieme ConnectGoogle Scholar
  • 9a Yamamoto Y. Togo H. Synlett  2006,  798 
    CrossrefGoogle Scholar
  • 9b Yamamoto Y. Kawano Y. Toy PH. Togo H. Tetrahedron  2007,  63:  4680 
    CrossrefGoogle Scholar
  • 10 Akiike J. Yamamoto Y. Togo H. Synlett  2007,  2168 
    Article in Thieme ConnectGoogle Scholar
  • 11 Typical Experimental Procedure: To a mixture of iodobenzene (purity 98%, 1.1 mmol, 228 mg) and MCPBA (purity 65%, 292 mg) in MeCN (8 mL) was added TfOH (2.0 mmol, 0.17 mL). The obtained mixture was stirred for 0.5 h at r.t. under an argon atmosphere. Then, a solution of acetophenone (purity 98.5%, 1.0 mmol, 122 mg) in MeCN (2 mL) was added, and the mixture was stirred for 2 h under refluxing conditions. After the reaction, the reaction mixture was poured into sat. aq NaHCO3 solution and extracted with CHCl3 (3 × 30 mL). The organic layer was dried over Na2SO4. After filtration and removal of the solvent under reduced pressure, the residue was purified by preparative TLC on silica gel (eluent: hexane-EtOAc, 5:1) to give 2-methyl-5-phenyloxazole in 56% yield. 2-Methyl-5-phenyloxazole: mp 57-58.5 °C (lit.12 mp 57-58 °C). IR (KBr): 1580, 1560, 1480 cm-1. 1H NMR (400 MHz, CDCl3): δ = 2.53 (s, 3 H), 7.20 (s, 1 H), 7.30 (tt, J = 1.5, 7.8 Hz, 1 H), 7.40 (t, J = 7.8 Hz, 2 H), 7.60 (dd, J = 1.5, 7.8 Hz, 2 H). MS (FAB): m/z = 160 [M + H].Analytical data for selected oxazoles are as follows: 2-Methyl-5-(4′-chlorophenyl)oxazole: mp 71-72 °C (lit.13 mp 74-75.5 °C). IR (KBr): 3060, 1580, 1560, 1480, 1090, 820 cm-1. 1H NMR (400 MHz, CDCl3): δ = 2.53 (s, 3 H, s), 7.20 (s, 1 H), 7.38 (d, J = 8.9 Hz, 2 H), 7.54 (d, J = 8.9 Hz, 2 H). 2-Methyl-5-(4′-nitrophenyl)oxazole: mp 161-162 °C (lit.14 mp 167-168 °C). IR (KBr): 3020, 1610, 1560, 1500, 1350, 1330, 1130, 1110, 1060, 940, 850, 760 cm-1. 1H NMR (400 MHz, CDCl3): δ = 2.58 (s, 3 H), 7.42 (s, 1 H), 7.76 (d, J = 9.0 Hz, 2 H), 8.28 (d, J = 9.0 Hz, 2 H). MS (FAB): m/z = 205 [M + H]. 2-Methyl-5-(4′-methylphenyl)oxazole: mp 54-55 °C (lit.14 mp 56-57 °C). IR (KBr): 1580, 1560, 1500, 1460, 1380 cm-1. 1H NMR (400 MHz, CDCl3): δ = 2.37 (s, 3 H), 2.52 (s, 3 H), 7.15 (s, 1 H), 7.21 (d, J = 8.1 Hz, 2 H), 7.49 (d, J = 8.1 Hz, 2 H). 2-Ethyl-5-phenyloxazole: oil. IR (neat): 3060, 2980, 2940, 1580, 1560, 1490, 1450, 760, 690 cm-1. 1H NMR (400 MHz, CDCl3): δ = 1.40 (t, J = 7.6 Hz, 3 H), 2.86 (q, J = 7.6 Hz, 2 H), 7.22 (s, 1 H), 7.30 (tt, J = 1.4, 7.6 Hz, 1 H), 7.40 (dd, J = 7.6, 8.0 Hz, 2 H), 7.61 (dd, J = 1.4, 8.0 Hz, 2 H). HRMS: m/z [M + H] calcd for C11H12NO: 174.0919; found: 174.0922. 2-Ethyl-5-(4′-nitrophenyl)oxazole: mp 81-82 °C (lit.12 mp 85-86 °C). IR (KBr): 3120, 2990, 1620, 1560, 1500, 1330, 750 cm-1. 1H NMR (400 MHz, CDCl3): δ = 1.42 (t, J = 7.6 Hz, 3 H), 2.90 (q, J = 7.6 Hz, 2 H), 7.44 (s, 1 H), 7.76 (d, J = 9.0 Hz, 2 H), 8.28 (d, J = 9.0 Hz, 2 H)
  • 12 Lamattina JL. J. Org. Chem.  1980,  45:  2261 
    CrossrefGoogle Scholar
  • 13 Houwing HA. Wildeman J. Leusen AM. Tetrahedron Lett.  1976,  17:  143 
    CrossrefGoogle Scholar
  • 14 Ibata T. Sato R. Bull. Chem. Soc. Jpn.  1979,  52:  3597 
    CrossrefGoogle Scholar