Synlett 2009(6): 1019-1020  
DOI: 10.1055/s-0028-1088200
© Georg Thieme Verlag Stuttgart ˙ New York

Alkyl Orthoformate: A Versatile Reagent in Organic Synthesis

Clarissa Piccinin Frizzo*
Department of Chemistry, Federal University of Santa Maria, 97105-900 Santa Maria, RS, Brazil
Further Information

Publication History

Publication Date:
16 March 2009 (online)


Alkyl orthoformates are important intermediates for organic synthesis, widely used in medicines, pesticides and flavors. Alkyl orthoformates, in general, are transparent liquids that decompose in water and are soluble in methanol and chloroform. Alkyl orthoformates in acid media generate alkoxonium, which is a powerful electrophilic agent used as one carbon building block, and two alcohol molecules, which constitutes an important protecting groups. Alkyl orthoformates have also been reported as highly selective O, S and C-alkylating agents due to their ability to furnish methyl groups by releasing methyl formate, which is a good leaving group. Thus, alkyl orthoformates are versatile chemical reagents, used to supply nucleophilic oxygen and eletrophilic carbon atoms. Recent applications of alkyl orthoformates are shown below.


  • 1 Kumar R. Chauhan PMS. Tetrahedron Lett.  2008,  49:  5475 
  • 2 Hazarkhani H. Karimi B. Tetrahedron  2003,  59:  4757 
  • 3 Khosropour AR. Mohammadpoor-Baltork I. Ghorbankhani H. Tetrahedron Lett.  2006,  47:  3561 
  • 4 Narasimhulu M. Mahesh KC. Reddy TS. Rajesh K. Venkateswarlu Y. Tetrahedron Lett.  2006,  47:  4381 
  • 5 Merior E. Conrad J.  Chandi JC. Malakar C. Beifuss U. Synlett  2008,  903 
  • 6 Yadav JS. Kondaji G. Reddy MSR. Srihari PS. Tetrahedron Lett.  2008,  49:  3810 
  • 7 Kumamoto K. Ichikawa Y. Kotsuki H. Synlett  2005,  2254 
  • 8 Evans DA. Thomson RJ. J. Am. Chem. Soc.  2005,  127:  10506 
  • 9 Periasamy M. Kishorebabu N. Jayakumar KN. Tetrahedron Lett.  2007,  48:  1955 
  • 10 Martins MAP. Bastos GP. Bonacorso HG. Zanatta N. Flores AFC. Siqueira GM. Tetrahedron Lett.  1999,  40:  4309 
  • 11 Bonacorso HG. Lopes IS. Wastowski AD. Zanatta N. Martins MAP. J. Fluorine Chem.  2003,  120:  29 
  • 12 Flores AFC. Brondani S. Zanatta N. Rosa A. Martins MAP. Tetrahedron Lett.  2002,  43:  8701 
  • 13 Gesinski MR. Van Orden LJ. Rychnovsky SD. Synlett  2008,  363