Synthesis 2012; 44(16): 2527-2530
DOI: 10.1055/s-0031-1290944
special topic
© Georg Thieme Verlag Stuttgart · New York

Continuous-Flow Microliter Microwave Irradiation in the Synthesis of Isoxazole Derivatives: An Optimization Procedure

Antonio M. Rodriguez
a   Departamento de Química Orgánica, Facultad de Químicas, Universidad de Castilla-La Mancha, 13071 Ciudad Real, Spain
,
Alberto Juan
b   Instituto Regional de Investigación Científica Aplicada (IRICA), Universidad de Castilla-La Mancha, 13071 Ciudad Real, Spain, Fax: 34(9022)04130   Email: Antonio.Hoz@uclm.es
,
M. Victoria Gómez*
b   Instituto Regional de Investigación Científica Aplicada (IRICA), Universidad de Castilla-La Mancha, 13071 Ciudad Real, Spain, Fax: 34(9022)04130   Email: Antonio.Hoz@uclm.es
,
Andres Moreno
a   Departamento de Química Orgánica, Facultad de Químicas, Universidad de Castilla-La Mancha, 13071 Ciudad Real, Spain
,
Antonio de la Hoz*
a   Departamento de Química Orgánica, Facultad de Químicas, Universidad de Castilla-La Mancha, 13071 Ciudad Real, Spain
› Author Affiliations
Further Information

Publication History

Received: 01 March 2012

Accepted after revision: 15 March 2012

Publication Date:
20 April 2012 (online)


Abstract

An efficient method was developed for the synthesis of 3,4,5-trisubstituted and 3,5-disubstituted isoxazoles by using continuous-flow microwave-heated microreactors. A study on the separate effects of the temperature, continuous-flow regime, and microwave irradiation showed that the continuous-flow regime had important effects for less reactive diketones, where microwave heating enhanced the reaction, permitting the formation of 5-methyl-3-phenylisoxazole, which was not formed in the absence of microwaves.

 
  • References

  • 1 Wiles C, Watts P. Chem. Commun. (Cambridge) 2011; 47: 6512
  • 2 Ehrfeld W, Hessel V, Löwe H. Microreactors: New Technology for Modern Chemistry . Wiley-VCH; Weinheim: 2000
  • 3 Wiles C, Watts P. Eur. J. Org. Chem. 2008; 1655
    • 4a Díaz-Ortiz A, de la Hoz A, Moreno A. Curr. Org. Chem. 2004; 8: 903
    • 4b Díaz-Ortiz A, de la Hoz A, Moreno A. Adv. Org. Synth. 2005; 1: 119
  • 5 Shore G, Organ MG. Chem. Commun. (Cambridge) 2008; 838
  • 6 Gomez MV, Verputten H, Díaz-Ortiz A, Moreno A, de la Hoz A, Velders AH. Chem. Commun. (Cambridge) 2010; 46: 4514
  • 7 Belder D, Ludwig M, Wang L.-W, Reetz MT. Angew. Chem. Int. Ed. 2006; 45: 2463 ; Angew. Chem. 2006, 118, 2523
  • 8 Nelder JA, Mead R. Comput. J. 1965; 7: 308
  • 9 Hewings DS, Wang M, Philpott M, Fedorov O, Uttarkour S, Filippakopoulos P, Picaud S, Vuppusetty C, Marsden B, Knapp S, Conway SJ, Heightman TD. J. Med. Chem. 2011; 54: 6761
  • 10 Tang S, He J, Yongquan S, Liuer H, She X. Org. Lett. 2009; 11: 3982
  • 11 Wiles C, Watts P, Haswell SJ. Org. Process Res. Dev. 2004; 8: 28
    • 12a Viviano M, Glasnov TN, Reichart B, Tekautz G, Kappe CO. Org. Process Res. Dev. 2011; 15: 858
    • 12b Glasnov TN, Kappe CO. J. Heterocycl. Chem. 2011; 48: 11
    • 12c Wiles C, Watts P. Beilstein J. Org. Chem. 2011; 7: 1360
  • 13 Rodriguez, A. M.; de la Hoz, A.; Velders, A. H.; Fratila, R.; Gomez, M. V. manuscript in preparation
    • 14a Rodríguez AM, Cebrián C, Prieto P, García JI, de la Hoz A, Díaz-Ortiz A. Chem.–Eur. J. 2012; in press; DOI: 10.1002/chem.201103560
    • 14b Microreactors in Organic Synthesis and Catalysis. Wirth T. Wiley-VCH; Weinheim: 2008
  • 15 Griesbeck AG, Franke M, Neudörfl J, Kotaka H. Beilstein J. Org. Chem. 2011; 7: 127
  • 16 Kashima C, Yamamoto Y, Tsuda Y, Omote Y. Bull. Chem. Soc. Jpn. 1976; 49: 1047
    • 17a Sechi M, Sannia L, Orecchioni M, Carta F, Paglietti G, Neamati N. J. Heterocycl. Chem. 2003; 40: 1097
    • 17b Zaitsev AB, Schmidt EY, Mikhaleva AM, Afonin AV, Ushakov IA. Chem. Heterocycl. Compd. (N. Y., NY, U. S.) 2005; 41: 722