Download PDF
Synthesis 2010(2): 343-348  
DOI: 10.1055/s-0029-1217109
PAPER
© Georg Thieme Verlag Stuttgart ˙ New York

Intramolecular 1,3-Dipolar Cycloaddition of Alkenylnitrones of the 4H-Imidazole Series: Synthesis of a New Nitroxide pH-Sensitive Spin Probe

Denis A. Morozov*a,b, Igor A. Kirilyuka, Yuri V. Gatilova, Irina Yu. Bagryanskayaa, Julya Yu. Bozhkoc, Denis A. Komarovc, Igor A. Grigor’eva
a Novosibirsk Institute of Organic Chemistry SB RAS, ave. akad. Lavrentjeva 9, Novosibirsk 630090, Russian Federation
b Novosibirsk State University, Pirogova 2, Novosibirsk 630090, Russian Federation
Fax: +7(383)3309752; e-Mail: m_falcon@nioch.nsc.ru;
c Institute of Chemical Kinetics and Combustion SB RAS, Institutskaya 3, Novosibirsk 630090, Russian Federation
Further Information

Publication History

Received 11 August 2009
Publication Date:
06 November 2009 (online)

    Permissions and Reprints All articles of this category

Abstract

A new method was used for the preparation of a pH-sensitive spin probe involving an intramolecular 1,3-dipolar cycloaddition - reductive isoxazolidine ring-opening - oxidation reaction sequence. 2-(2-Allyloxyphenyl)-5-R-4,4-dimethyl-4H-imidazole-3-oxides (R = Me, NMe2), prepared from 3-hydroxylamino-3-methylbutan-2-one, undergo intramolecular 1,3-dipolar cycloaddition upon heating in toluene. Treatment of the cycloadducts with low-valence titanium (LVT) reagent resulted in reductive cleavage of the N-O bond of the isoxazolidine ring to give 3′-hydroxymethyl-5,5-dimethyl-4-R-2,5-dihydrospiro[imidazol-2,4′-chromane]s. The amine (R = NMe2) was then oxidized with MCPBA to the target nitroxide - 3′-hydroxymethyl-5,5-dimethyl-4-dimethylamino-2,5-dihydrospiro[imidazole-2,4′-chroman]-1-oxyl.

Key words

1,3-dipolar cycloaddition - low-valence titanium - nitroxide radical - 4H-imidazole 3-oxide - pH-sensitive spin probe

    References

  • 1 Zweier JL. Wang P. Samouilov A. Kuppusamy P. Nat. Med.  1995,  1:  804 
    CrossrefGoogle Scholar
  • 2 Bond JM. Chacon E. Herman B. Lemasters JJ. Am. J. Physiol.  1993,  265:  129 
    Google Scholar
  • 3 Ferrari LA. Giannuzzi L. Forensic Sci. Int.  2005,  153:  45 
    CrossrefGoogle Scholar
  • 4 Issberner U. Reeh PW. Steen KH. Neurosci. Lett.  1996,  208:  191 
    CrossrefGoogle Scholar
  • 5 Raghunand N. Gillies RJ. Drug Resist. Updates  2000,  3:  39 
    CrossrefGoogle Scholar
  • 6a Khramtsov VV. Grigor’ev IA. Foster MA. Lurie DJ. Nicholson I. Cell. Mol. Biol.  2000,  46:  1361 
    Google Scholar
  • 6b Potapenko DI. Foster MA. Lurie DJ. Kirilyuk IA. Hutchison JMS. Grigor"ev IA. Bagryanskaya EG. Khramtsov VV. J. Magn. Reson.  2006,  182:  1 
    Google Scholar
  • 6c Khramtsov VV. Curr. Org. Chem.  2005,  9:  909 
    Google Scholar
  • 7 Khramtsov VV. Volodarsky LB. In Spin Labeling. The Next Millennium   Berliner LJ. Plenum Press; New York: 1998.  p.109-180  
    Google Scholar
  • 8 Kirilyuk IA. Shevelev TG. Morozov DA. Khromovskih EL. Skuridin NG. Khramtsov VV. Grigor’ev IA. Synthesis  2003,  871 
    Article in Thieme ConnectGoogle Scholar
  • 9 Woldman YaY. Semenov SV. Bobko AA. Kirilyuk IA. Polienko JF. Voinov MA. Bagryanskaya EG. Khramtsov VV. The Analyst  2009,  134:  904 
    CrossrefGoogle Scholar
  • 10 Sár CP. Õsz E. Jekõ J. Hideg K. Synthesis  2005,  255 
    Article in Thieme ConnectGoogle Scholar
  • 11 Bakunova SM. Kirilyuk IA. Grigor’ev IA. Russ. Chem. Bull. (Engl. Transl.)  2001,  50:  882 
    CrossrefGoogle Scholar
  • 12a Jones RCF. Martin JN. Nitrones, In Synthetic Applications of 1,3-Dipolar Cycloaddition Chemistry Toward Heterocycles and Natural Products   Padwa A. Pearson WH. Wiley-IEEE; New York: 2003.  p.55 
    Google Scholar
  • 12b Voinov MA. Grigor’ev IA. Volodarsky LB. Tetrahedron  2000,  56:  4071 
    Google Scholar
  • 12c Grigor’ev IA. Nitrones: Novel Strategies in Synthesis   Feuer H. Wiley; New York: 2008.  p.129 
    Google Scholar
  • 13a Marx L. Chiarelli R. Guiberteau T. Rassat A. J. Chem. Soc., Perkin Trans. 1  2000,  1181 
    Google Scholar
  • 13b Kirilyuk IA. Bobko AA. Grigor"ev IA. Khramtsov VV. Org. Biomol. Chem.  2004,  2:  1025 
    Google Scholar
  • 14 Kirilyuk IA. Morozov DA. Tabatchikova YuS. Medvedev VS. Lebedev AV. Romanenko GV. Rybalova TV. Grigor"ev IA. Russ. Chem. Bull. (Engl. Transl.)  2008,  57:  1516 ; Izv. Akad. Nauk, Ser. Khim 2008, 7, 1487
    CrossrefGoogle Scholar
  • 15 Oppolzer W. Keller K. Tetrahedron Lett.  1970,  1117 
    CrossrefGoogle Scholar
  • 16a Ali SkA. Wazeer MIM. Tetrahedron  1993,  49:  4339 
    Google Scholar
  • 16b Holmes AB. Hughes AB. Smith AL. Synlett  1991,  47 
    Google Scholar
  • 16c Dehnel A. Griller D. Kanabus-Kaminska JM. J. Org. Chem.  1988,  53:  1566 
    Google Scholar
  • 16d Akhrem AA. Lakhvich FA. Khripach VA. Chem. Heterocycl. Compd. (Engl. Transl.)  1981,  853 
    Google Scholar
  • 16e Kotyatkina AI. Zhabinsky VN. Khripach VA. Russ. Chem. Rev. (Engl. Transl.)  2001,  70:  641 
    Google Scholar
  • 16f Curran DP. J. Am. Chem. Soc.  1983,  105:  5826 
    Google Scholar
  • 16g Iida H. Kasahara K. Kibayashi C. J. Am. Chem. Soc.  1986,  108:  4647 
    Google Scholar
  • 16h Cicchi S. Revuelta J. Zanobini A. Betti M. Brandi A. Synlett  2003,  2305 
    Google Scholar
  • 16i Wovkulich PM. Uskokovic MR. Tetrahedron  1985,  41:  3455 
    Google Scholar
  • 16j Merino P. Anoro S. Franco S. Gascon JM. Martin V. Merchan FL. Revuelta J. Tejero T. Tunon V. Synth. Commun.  2000,  30:  2989 
    Google Scholar
  • 17 Churykau DH. Zinovich VG. Kulinkovich OG. Synlett  2004,  1949 
    Article in Thieme ConnectGoogle Scholar
  • 19 Yoshioka T. Higashida S. Murayama K. Bull. Chem. Soc. Jpn.  1972,  45:  636 
    CrossrefGoogle Scholar
  • 20 Kocherginsky N. Swartz HM. Nitroxide spin labels, reactions in biology and chemistry   CRC Press; Boca Raton: 1995.  p.1 
    Google Scholar
  • 21 Kirilyuk IA. Bobko AA. Khramtsov VV. Grigor’ev IA. Org. Biomol. Chem.  2005,  3:  1269 
    CrossrefGoogle Scholar
  • 22 Volodarskii LB. Sevastyanova TK. Zh. Org. Khim.  1971,  8:  1971 ; Chem. Abstr. 1971, 75, 140425
    Google Scholar
18

CCDC-742584 (10b) and CCDC-742583 (1) contain all the crystallographic details for this publication. These are available free of charge at www.ccdc.cam.ac.uk/conts/retrieving.html or can be ordered from the following address: Cambridge Crystallographic Data Centre, 12 Union Road, Cambridge, CB2 1EZ, UK; Fax: +44(1223)336033, or deposit@ccdc.cam.ac.uk.