Download PDF
Synthesis 2010(4): 678-688  
DOI: 10.1055/s-0029-1218581
PAPER
© Georg Thieme Verlag Stuttgart ˙ New York

Synthesis of N-(Benzyloxyethyl)- and N-(Alkoxycarbonylmethyl)nitrones

Alba Diez-Martinez, Zeynep Gultekin, Ignacio Delso, Tomas Tejero, Pedro Merino*
Laboratorio de Sintesis Asimetrica, Departamento de Quimica Organica, Instituto de Ciencia de Materiales de Aragón, Universidad de Zaragoza - CSIC, 50009 Zaragoza, Aragon, Spain
Fax: +34(976)762075; e-Mail: pmerino@unizar.es;
Further Information

Publication History

Received 5 October 2009
Publication Date:
27 November 2009 (online)

    Permissions and Reprints All articles of this category

Abstract

Highly efficient procedures for the preparation of nitrones bearing an oxygenated functionality at the β-position of the nitrone nitrogen, via either condensation of hydroxylamines with aldehydes or oxidation of the precursor imine, are described. The reactions proceeded smoothly at ambient temperature and the desired products were obtained in high to excellent yields. A total of 45 nitrones and 16 single-crystal analyses have been obtained.

Key words

nitrones - hydroxylamines - oxidation - aldehydes - condensation

    References

  • 1a Merino P. In Targets in Heterocyclic Systems: Chemistry and Properties   Vol. 7:  Attanasi OA. Spinelli D. Italian Society of Chemistry; Rome: 2003.  p.140 
    Google Scholar
  • 1b Merino P. Franco S. Merchan FL. Tejero T. Synlett  2000,  442 
    Google Scholar
  • 1c Lombardo M. Trombini C. Synthesis  2000,  759 
    Google Scholar
  • 1d Lombardo M. Trombini C. Curr. Org. Chem.  2002,  6:  695 
    Google Scholar
  • 2a Martin JN. Jones RCF. In Synthetic Applications of 1,3-Dipolar Cycloaddition Chemistry toward Heterocycles and Natural Products   Padwa A. Pearson WH. Wiley; Chichester: 2002.  p.1 
    Google Scholar
  • 2b Osborn HMI. Gemmell N. Harwood LM. J. Chem. Soc., Perkin Trans. 1  2002,  2419 
    Google Scholar
  • 2c Gothelf KV. Jorgensen KA. Chem. Commun.  2000,  1449 
    Google Scholar
  • 2d Koumbis AE. Gallos JK. Curr. Org. Chem.  2003,  7:  585 
    Google Scholar
  • 2e Frederickson M. Tetrahedron  1997,  53:  403 
    Google Scholar
  • 3 Greenwood-van Meerveld B. Tyler KR. Am. J. Pharm. Toxicol.  2006,  1:  54 
    Google Scholar
  • 4 Robertson L. Hartley RC. Tetrahedron  2009,  65:  5284 
    CrossrefPubMedGoogle Scholar
  • 5 Floyd RA. Aging Cell  2006,  5:  51 
    CrossrefPubMedGoogle Scholar
  • 6 Green AR. Ashwood T. Odergren T. Jackson DM. Pharmacol. Ther.  2003,  100:  195 
    CrossrefPubMedGoogle Scholar
  • For general reviews on nitrones as therapeutics see:
  • 7a Floyd RA. Kopke RD. Choi C.-H. Foster SB. Doblas S. Towner RA. Free Radical Biol. Med.  2008,  45:  1361 
    Google Scholar
  • 7b Maples KR. Green AR. Floyd RA. CNS Drugs  2004,  18:  1071 
    Google Scholar
  • 7c Floyd RA. Hensley K. In Neuroinflammation   2nd ed.:  Wood PL. Humana Press; Totowa NJ: 2003.  p.171 
    Google Scholar
  • 8 Merino P. In Science of Synthesis   Vol. 27:  Padwa A., Bellus D., Thieme; Stuttgart: 2004.  p.511 
    Google Scholar
  • 9 Dondoni A. Franco S. Junquera F. Merchan F. Merino P. Tejero T. Synth. Commun.  1994,  24:  2537 
    CrossrefGoogle Scholar
  • 10 Franco S. Merchan FL. Merino P. Tejero T. Synth. Commun.  1995,  25:  2275 
    CrossrefGoogle Scholar
  • 11 Revuelta J. Cicchi S. Goti A. Brandi A. Synthesis  2007,  485 
    Article in Thieme ConnectGoogle Scholar
  • 12a Merino P. Mannucci V. Tejero T. Eur. J. Org. Chem.  2008,  3943 
    Google Scholar
  • 12b Merino P. Jimenez P. Tejero T. J. Org. Chem.  2006,  71:  4685 
    Google Scholar
  • 12c Chiacchio U. Rescifina A. Saita MG. Iannazzo D. Romeo G. Mates JA. Tejero T. Merino P. J. Org. Chem.  2005,  70:  8991 
    Google Scholar
  • 12d Merino P. Revuelta J. Tejero T. Chiacchio U. Rescifina A. Piperno A. Romeo G. Tetrahedron: Asymmetry  2002,  13:  167 
    Google Scholar
  • 12e Merino P. Franco S. Merchan FL. Tejero T. J. Org. Chem.  2000,  65:  5575 
    Google Scholar
  • 12f Merino P. Castillo E. Franco S. Merchan FL. Tejero T. J. Org. Chem.  1998,  63:  2371 
    Google Scholar
  • 12g Merino P. Lanaspa A. Merchan FL. Tejero T. Tetrahedron: Asymmetry  1998,  9:  629 
    Google Scholar
  • 12h Dondoni A. Franco S. Junquera F. Merchan FL. Merino P. Tejero T. J. Org. Chem.  1997,  62:  5497 
    Google Scholar
  • For representative papers illustrating the synthetic utility of this sort of nitrones see:
  • 13a Ali SA. Iman ZM. Tetrahedron  2007,  63:  9134 
    Google Scholar
  • 13b Hubregtse T. Hanefeld U. Arends IWCE. Eur. J. Org. Chem.  2007,  2413 
    Google Scholar
  • 13c Hanselman R. Zhou J. Ma P. Confalone PN. J. Org. Chem.  2003,  68:  8739 
    Google Scholar
  • 13d Patel SK. Murat K. Py S. Vallee Y. Org. Lett.  2003,  5:  4081 
    Google Scholar
  • 13e Tamura O. Gotanda K. Yoshino J. Morita Y. Terashima R. Kikuchi M. Miyawaki T. Mita N. Yamashita M. Ishibashi H. Sakamoto M. J. Org. Chem.  2000,  65:  8544 
    Google Scholar
  • 14 Tokuyama H. Kuboyama T. Amano A. Yamashita T. Fukuyama T. Synthesis  2000,  1299 
    Article in Thieme ConnectGoogle Scholar
  • 15 Soldani G. Cardona F. Goti A. Org. Lett.  2007,  9:  473 
    CrossrefPubMedGoogle Scholar
  • 16 For application of the MeReO3/UHP system to the oxidation of secondary amines to nitrones see: Goti A. Cardona F. Soldani G. Org. Synth.  2005,  81:  204 
    CrossrefGoogle Scholar
  • 17 Aromatic solvent induced shift, see: Aurich H.-G. Franzke M. Kesselheim HP. Tetrahedron  1992,  48:  663 
    CrossrefGoogle Scholar
  • 19a Wolfe S. Akuche C. Ro S. Wilson M.-C. Kim C.-K. Shi Z. Can. J. Chem.  2003,  81:  915 
    Google Scholar
  • 19b Buehler E. Brown GB. J. Org. Chem.  1967,  32:  265 
    Google Scholar
  • 19c Polonski T. Chimiak A. J. Org. Chem.  1976,  41:  2092 
    Google Scholar
  • 19d Goto G. Kawakita K. Okutani T. Miki T. Chem. Pharm. Bull.  1986,  34:  3202 
    Google Scholar
  • 19e Hercheid JM. Ottenheijm HCJ. Tetrahedron Lett.  1978,  19:  5143 
    Google Scholar
  • 19f Hu J. Miller MJ. J. Am. Chem. Soc.  1997,  119:  3462 
    Google Scholar
  • 19g Polonski T. Chimiak A. Tetrahedron Lett.  1974,  15:  2453 
    Google Scholar
  • 20 Nguyen TB. Martel A. Dhal R. Dujardin G. Synthesis  2009,  3174 
    Article in Thieme ConnectGoogle Scholar
18

The authors have deposited the atomic coordinates for these structures with the Cambridge Crystallographic Data Centre. Deposition numbers are as follows: 1a, CCDC 753240; 1c, CCDC 753241; 1d, CCDC 753242; 1f, CCDC 753243; 1h, CCDC 753244; 1i, CCDC 753245; 1j, CCDC 753246; 1k, CCDC 753247; 2a, CCDC 753248; 2b, CCDC 753249; 2d, CCDC 753250; 2f, CCDC 753251; 2g, CCDC 753252; 2j, CCDC 753253; 2n, CCDC 753254; 2q, CCDC 753255. The coordinates can be obtained on request from the Director, Cambridge Crystallographic Data Centre, 12 Union Road, Cambridge CB2 1EZ, UK.