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Synlett 2014; 25(08): 1137-1141
DOI: 10.1055/s-0033-1340981
letter
© Georg Thieme Verlag Stuttgart · New York

A Facile and Expeditious One-Pot Synthesis of α-Keto-1,3,4-oxadiazoles

Dalip Kumar*
Department of Chemistry, Birla Institute of Technology and Science, Pilani – 333 031, Rajasthan, India   Fax: +44(113)3436565   Email: dalipk@pilani.bits-pilani.ac.in
,
Meenakshi Pilania
Department of Chemistry, Birla Institute of Technology and Science, Pilani – 333 031, Rajasthan, India   Fax: +44(113)3436565   Email: dalipk@pilani.bits-pilani.ac.in
,
V. Arun
Department of Chemistry, Birla Institute of Technology and Science, Pilani – 333 031, Rajasthan, India   Fax: +44(113)3436565   Email: dalipk@pilani.bits-pilani.ac.in
,
Bhupendra Mishra
Department of Chemistry, Birla Institute of Technology and Science, Pilani – 333 031, Rajasthan, India   Fax: +44(113)3436565   Email: dalipk@pilani.bits-pilani.ac.in
› Author Affiliations
Further Information

Publication History

Received: 24 December 2013

Accepted after revision: 19 February 2014

Publication Date:
24 March 2014 (online)

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Abstract

An efficient and high-yielding protocol for the preparation of α-keto-1,3,4-oxadiazoles has been developed. Formation of α-keto-1,3,4-oxadiazoles involves the 2-iodoxybenzoic acid/tetraethylammonium bromide mediated oxidative cyclization of hydrazide-hydrazones generated in situ from the reaction of aryl glyoxal and hydrazides. This one-pot protocol is reasonably general for the preparation of α-keto-1,3,4-oxadiazoles under mild conditions in short reaction times.

Key words

nitrogen heterocycles - hypervalent iodine reagents - oxidation - cyclization
 

  • References and Notes

    • 1a Amir M, Shikha K. Eur. J. Med. Chem. 2004; 39: 535
      Crossref
    • 1b Rapolu S, Alla M, Bommena VR, Murthy R, Jain N, Bommareddy VR, Bommineni MR. Eur. J. Med. Chem. 2013; 66: 91
      Crossref
    • 1c de Oliveira CS, Lira BF, Barbosa-Filho JM, Lorenzo JG. F, de Athayde-Filho PF. Molecules 2012; 17: 10192
      Crossref
    • 2a Xie Y, Liu J, Yang P, Shi X, Li J. Tetrahedron 2011; 67: 5369
      Crossref
    • 2b Stabile P, Lamonica A, Ribecai A, Castoldi D, Guercio G, Curcuruto O. Tetrahedron Lett. 2010; 51: 4801
      Crossref
  • 3 Guin S, Ghosh T, Rout SK, Banerjee A, Patel BK. Org. Lett. 2011; 13: 5976
    CrossrefPubMed
    • 4a Dohi T, Ito M, Yamaoka N, Morimoto K, Fujioka H, Kita Y. Tetrahedron 2009; 65: 10797
      Crossref
    • 4b Zhdankin VV, Stang PJ. Chem. Rev. 2008; 108: 5299
      CrossrefPubMed
    • 4c Silva JL. F, Olofsson B. Nat. Prod. Rep. 2011; 28: 1722
      Crossref
    • 4d Zhdankin VV. J. Org. Chem. 2011; 76: 1185
      Crossref
    • 4e Kumar D, Arun V, Maruthi Kumar N, Acosta G, Noel B, Shah K. ChemMedChem 2012; 7: 1915
      Crossref
    • 4f Tantak MP, Kumar A, Noel B, Shah K, Kumar D. ChemMedChem 2013; 8: 1468
      Crossref
    • 4g Duschek A, Kirsch SF. Angew. Chem. Int. Ed. 2011; 50: 1524
      CrossrefPubMed
    • 4h Satam V, Harad A, Rajule R, Pati H. Tetrahedron 2010; 66: 7659
      Crossref
    • 5a Ghosh H, Yella R, Ali AR, Sahoo SK, Patel BK. Tetrahedron Lett. 2009; 50: 2407
      Crossref
    • 5b Singh CB, Ghosh H, Murru S, Patel BK. J. Org. Chem. 2008; 73: 2924
      CrossrefPubMed
    • 5c Vaddula B, Leazer J, Varma RS. Adv. Synth. Catal. 2012; 354: 986
      Crossref
    • 6a Moriarty RM. J. Org. Chem. 2005; 70: 2893
      CrossrefPubMed
    • 6b Prabhu G, Sureshbabu VV. Tetrahedron Lett. 2012; 53: 4232
      Crossref
    • 6c Stang PJ, Zhdankin VV. Chem. Rev. 1996; 96: 1123
      CrossrefPubMed
  • 7 Donohoe TJ, Kabeshov MA, Rathi AH, Smith IE. D. Org. Biomol. Chem. 2012; 10: 1093
    Crossref
  • 8 Moorthy JN, Neogi I. Tetrahedron Lett. 2011; 52: 3868
    Crossref
  • 9 Wagh YS, Tiwari NJ, Bhanage BM. Tetrahedron Lett. 2013; 54: 1290
    Crossref
  • 10 Prabhu G, Sureshbabu VV. Tetrahedron Lett. 2012; 53: 4232
    Crossref
  • 11 Palmer JT, Hirschbein BL, Cheung H, McCarter J, Janc JW, Yu ZW, Wesolowski G. Bioorg. Med. Chem. Lett. 2006; 16: 2909
    Crossref
  • 12 Ohmoto K, Yamamoto T, Okuma M, Horiuchi T, Imanishi H, Odagaki Y, Kawabata K, Sekioka T, Hirota Y, Matsuoka S, Nakai H, Toda M, Cheronis JC, Spruce LW, Gyorkos A, Wieczorek M. J. Med. Chem. 2001; 44: 1268
    Crossref
  • 13 Otrubova K, Boger DL. ACS Chem. Neurosci. 2011; 3: 340
  • 14 Rydzewski RM, Burrill L, Mendonca R, Palmer JT, Rice M, Tahilramani R, Bass KE, Leung L, Gjerstad E, Janc JW, Pan L. J. Med. Chem. 2006; 49: 2953
    Crossref
    • 15a Lu Y, Li C.-M, Wang Z, Ross CR, Chen J, Dalton JT, Li W, Miller DD. J. Med. Chem. 2009; 52: 1701
      Crossref
    • 15b Xiao M, Ahn S, Wang J, Chen J, Miller DD, Dalton JT, Li W. J. Med. Chem. 2013; 56: 3318
      Crossref
  • 16 El Sayed KA. Phytochemistry 2000; 53: 675
    Crossref
  • 17 Kudelko A. Tetrahedron 2011; 67: 8502
    Crossref
  • 18 Zarudnitskii EV, Pervak II, Merkulov AS, Yurchenko AA, Tolmachev AA. Tetrahedron 2008; 64: 10431
    Crossref
  • 19 Cui L, Liu Q, Yu J, Ni C, Yu H. Tetrahedron Lett. 2011; 52: 5530
    Crossref
  • 20 Bellale EV, Bhalerao DS, Akamanchi KG. J. Org. Chem. 2008; 73: 9473
    Crossref
  • 21 One-Pot Synthesis of 4a–m; General Procedure: A mixture of arylglyoxal (1 mmol) and arylhydrazide (1 mmol) was stirred in acetonitrile at r.t. for 3 h. After consumption of the starting materials, IBX (1 mmol) was added to the reaction mixture followed by addition of TEAB (1.2 mmol) and stirring was continued at r.t. for another 3 h. Upon completion of the reaction, solvent was removed in vacuo and the crude material thus obtained was diluted with H2O and extracted with EtOAc (3 × 25 mL). The combined organic layers were washed with saturated NaHCO3 (20 mL), brine (20 mL), and dried over anhydrous Na2SO4. After filtration, the solvent was evaporated under reduced pressure and the residue was recrystallized from ethanol to afford analytically pure α-keto-1,3,4-oxadiazoles 4a–m in excellent yields. Phenyl(5-phenyl-1,3,4-oxadiazol-2-yl)methanone (4a): Yield: 90%; white solid; mp 143–144 °C (Lit.19 143–145 °C). IR (KBr): 1666, 1535, 1411, 1380, 1280, 1180 cm–1. 1H NMR (400 MHz, DMSO-d 6): δ = 8.45 (dd, J = 8.3, 1.1 Hz, 2 H), 8.15 (dd, J = 8.2, 1.3 Hz, 2 H), 7.74 (t, J = 7.4 Hz, 1 H), 7.64–7.56 (m, 5 H). 13C NMR (101 MHz, DMSO-d 6): δ = 182.13, 170.13, 165.71, 139.76, 139.31, 137.90, 135.60, 134.48, 133.78, 132.43, 127.70. MS (ESI): m/z [M + H]+ calcd for C15H10N2O2: 251.08; found: 251.1. Phenyl(5-p-tolyl-1,3,4-oxadiazol-2-yl)methanone (4b): Yield: 91%; white solid; mp 142–143 °C (Lit.19 139–141 °C). IR (KBr): 1659, 1489, 1450, 1381, 1265, 1173 cm–1. 1H NMR (400 MHz, DMSO-d 6): δ = 8.47 (dd, J = 8.4, 1.2 Hz, 2 H), 8.06–8.04 (m, 2 H), 7.79–7.75 (m, 1 H), 7.65–7.61 (m, 2 H), 7.45 (d, J = 8 Hz, 2 H), 2.46 (s, 3 H). 13C NMR (101 MHz, DMSO-d 6): δ = 176.85, 165.49, 160.26, 143.13, 134.36, 133.64, 130.27, 129.66, 128.39, 127.13, 119.47, 21.17. MS (ESI): m/z [M + H]+ calcd for C16H12N2O2: 265.1; found: 265.2. [5-(4-Methoxyphenyl)-1,3,4-oxadiazol-2-yl]phenyl-methanone (4c): Yield: 91%; white crystalline solid; mp 169.6–170 °C. IR (KBr): 1612, 1574, 1551, 1489, 1380, 1285 cm–1. 1H NMR (500 MHz, DMSO-d 6): δ = 8.41 (d, J = 7.7 Hz, 2 H), 8.10 (d, J = 8.5 Hz, 2 H), 7.81 (t, J = 7.2 Hz, 1 H), 7.68 (t, J = 7.5 Hz, 2 H), 7.23 (d, J = 8.5 Hz, 2 H), 3.89 (s, 3 H). MS (ESI): m/z [M + H]+ calcd for C16H12N2O3: 281.09; found: 281.2.
  • 22 One-Pot Synthesis of 7a–e; General Procedure: A mixture of arylglyoxal (1 mmol) and 2-hydrazinopyridine (1 mmol) was stirred in acetonitrile at r.t. for 5 min. Subsequently, IBX (1 mmol) was added to the reaction mixture, followed by the addition of TEAB (1.2 mmol) in portions. The resulting mixture was stirred at r.t. for 15 min. Upon completion of the reaction, solvent was removed in vacuo, the contents were diluted with H2O, and the mixture was extracted with EtOAc (3 × 25 mL). The combined organic layers were washed with saturated NaHCO3 (20 mL), brine (20 mL), and dried over anhydrous Na2SO4. After filtration, the solvent was removed under reduced pressure and the residue thus obtained was recrystallized from ethanol to afford α-keto-1,2,4-triazolo[4,3-a]pyridines 7a–e in excellent yields. (1,2,4-Triazolo[4,3-a]pyridine-3-yl)phenylmethanone (7a): Yield: 90%; light-yellow solid; mp 167 °C. IR (KBr): 1658, 1573, 1496, 1450, 1411, 1380 cm–1. 1H NMR (400 MHz, DMSO-d 6): δ = 9.51 (dd, J = 7.0, 1.0 Hz, 1 H), 8.51 (dd, J = 5.2, 3.3 Hz, 2 H), 8.05 (dd, J = 8.1, 1.0 Hz, 1 H), 7.73–7.67 (m, 2 H), 7.62–7.57 (m, 2 H), 7.32 (t, J = 7.4 Hz, 1 H). MS (ESI): m/z [M + H]+ calcd for C13H10N3O: 224.08; found: 224.2.