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Synlett 2004(5): 0874-0876  
DOI: 10.1055/s-2004-820013
LETTER
© Georg Thieme Verlag Stuttgart · New York

A New, Convenient, Highly Selective Free-Radical Hydroxymethylation of Heteroaromatic Bases by Persulfate Oxidation of Ethylene Glycol and Glycerol, Catalysed by AgNO3

Francesco Minisci*a, Ombretta Portaa, Francesco Recuperoa, Carlo Puntaa, Cristian Gambarottia, Barbara Prunaa, Monica Pierinia, Francesca Fontanab
a Dipartimento di Chimica, Materiali e Ingegneria Chimica G. Natta, Politecnico di Milano, via Mancinelli, 7, 20133 Milano, Italy
e-Mail: francesco.minisci@polimi.it;
b Dipartimento di Ingegneria Industriale, Università di Bergamo, viale Marconi 5, 24044 Dalmine BG, Italy
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Publication History

Received 19 December 2003
Publication Date:
24 February 2004 (online)

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Abstract

A new, convenient and selective source of hydroxymethyl (•CH2OH) radical has been developed by persulfate oxidation of ethylene glycol with AgNO3 catalysis. The •CH2OH radical is selectively trapped by protonated heteroaromatic bases, providing a new, general process of hydroxymethylation; the importance of the β-scission of the alkoxyl radical intermediate is emphasised.

Key words

hydroxymethylation - heterocycles - free-radicals - diols - persulfate

    References

  • 1 Studer A. Bossart M. In Radicals in Organic Synthesis   Renaud F. Sibi MP. Wiley-VCH; New York: 2001.  p.74 
    Google Scholar
  • Reviews on the subject:
  • 2a Minisci F. Porta O. In Advances in Heterocyclic Chemistry   Vol. 16:  Katritzky AR. Academic Press; New York: 1974.  p.123-180  
    CrossrefGoogle Scholar
  • 2b Minisci F. Top. Curr. Chem.  1976,  62:  1 
    CrossrefGoogle Scholar
  • 2c Minisci F. Fontana F. Vismara E. J. Heterocycl. Chem.  1990,  27:  79 
    CrossrefGoogle Scholar
  • Recent publications:
  • 3a Cowden CJ. Org. Lett.  2003,  5:  4497 
    Google Scholar
  • 3b Minisci F. Recupero F. Punta C. Gambarotti C. Pedulli GF. Fontana F. Chem. Commun.  2002,  2496 
    Google Scholar
  • 3c Minisci F. Recupero F. Cecchetto A. Punta C. Gambarotti C. Pedulli GF. Fontana F. J. Heterocycl. Chem.  2003,  40:  325 
    Google Scholar
  • 4 Recupero F. Bravo A. Bjorsvik H.-R. Fontana F. Minisci F. Piredda M. J. Chem. Soc., Perkin Trans. 2  1997,  2399 
    CrossrefGoogle Scholar
  • 5 Minisci F. In Substituent Effects in Radical Chemistry   Viehe HG. D. Reidel Publ. Co.; Dordrecht: 1986.  p.391-433  
    Google Scholar
  • 6 Fleming I. Frontier Orbitals and Organic Chemical Reactions   Wiley; Chichester: 1976. 
    Google Scholar
  • 7 Klopman G. J. Am. Chem. Soc.  1968,  90:  223 
    CrossrefGoogle Scholar
  • 8 Minisci F. Citterio A. Vismara E. Giordano C. Tetrahedron  1985,  41:  4157 
    CrossrefGoogle Scholar
  • 9 Clerici A. Minisci F. Ogawa K. Surzur JM. Tetrahedron Lett.  1978,  1149 
    CrossrefGoogle Scholar
  • 10 Avila DV. Brown CE. Ingold KU. Lusztyk J. J. Am. Chem. Soc.  1993,  115:  466 
    CrossrefGoogle Scholar
  • 11 Minisci F. Vismara E. Fontana F. Morini G. Serravalle M. Giordano C. J. Org. Chem.  1987,  52:  730 
    CrossrefGoogle Scholar
  • 12 Counterberger G. Steckam E. Blechert S. Angew. Chem. Int. Ed.  1998,  37:  660 
    CrossrefGoogle Scholar
13

Typical Experimental Procedure: Lepidine (20 mmol), CF3COOH (20 mmol), (NH4)2S2O8 (80 mmol) and AgNO3 (2 mmol) were refluxed in H2O (75 mL) and ethylene glycol (75 mL) for 3 h. The solution was made basic by NaOH and extracted with CH2Cl2. GC analysis (quinoline as internal standard) revealed the presence of 2-hydroxymethyllepidine (18.5 mmol) and lepidine (1.3 mmol). The CH2Cl2 solution was evaporated and the residue gave, by flash chromato-graphy (hexane-EtOAc, 2:1) pure 2-hydroxymethyllepidine (17.1 mmol), identified by comparison with an authentic sample. The results in the Table 1 refer to GC analyses.