Synlett 2013; 24(5): 657-658
DOI: 10.1055/s-0032-1318170
© Georg Thieme Verlag Stuttgart · New York


Aurélie Claraz
Université de Rouen, Laboratory COBRA UMR 6014 & FR 3038, IRCOF, 1 Rue Tesnière, 76821 Mont Saint Aignan Cedex, France; INSA de Rouen, Avenue de l’Université, 76800 St Etienne du ­Rouvray, France   Email:
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Further Information

Publication History

Publication Date:
08 February 2013 (online)


N,O-Bis(trimethylsilyl)acetamide (BSA) is a colorless liquid with a boiling point of 71–73 °C/35 mmHg. It is extremely moisture sensitive and can also be rapidly contaminated with trimethylsilylacetamide and acetamide. The reagent is commercially available and can be prepared from acetamide with an excess of triethylamine and chlorotrimethylsilane (Scheme [1]).[ 1 ] Since the early use of BSA in chromatographic analysis for the preparation of volatile trimethylsilyl derivatives, it has also proved to be useful in many synthetic applications.[ 2 ] At first, BSA has been used as a powerful silylating agent for the protection of amines, amides, carboxylic acids, alcohols, enols and phenols. In these cases, BSA is an attractive alternative to other silylating agents, such as trimethylsilyl chloride. Indeed, the reaction conditions are generally mild and neutral, and the byproducts are sufficiently volatile to be easily removed from the reaction mixture by evaporation under reduced pressure. It has also been used as a Brønsted base precursor in Tsuji–Trost reactions. More recently, it has been used to activate various functional groups during the formation of nucleosides, peptides and heterocycles to name but a few.

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Scheme 1 Synthesis of N,O-Bis(trimethylsilyl)acetamide
  • References

    • 1a Birkofer L, Ritter A, Giessler W. Angew. Chem., Int. Ed. Engl. 1963; 2: 96
    • 1b Klebe JF, Finkbeiner H, White DM. J. Am. Chem. Soc. 1966; 88: 3390
  • 2 El Gihani MT, Heaney H. Synthesis 1998; 357
  • 3 Niedballa U, Vorbrüggen H. J. Org. Chem. 1974; 39: 3654
  • 4 Bookser BC, Raffaele NB. J. Org. Chem. 2007; 72: 173
  • 5 Wu W, Zhang Z, Liebesland LS. J. Am. Chem. Soc. 2011; 133: 14256
  • 6 Chen H, He M, Wang Y, Zhai Y, Cui Y, Li Y, Li Y, Zhou H, Hong X, Deng Z. Green Chem. 2011; 13: 2723
  • 7 Wróbel Z, Wojciechowski K, Kwast A, Gadja N. Synlett 2010; 2435
  • 8 Bourgeois D, Craig D, King NP, Mountford DM. Angew. Chem. Int. Ed. 2005; 44: 618-621
    • 9a Craig D, King NP, Kley JT, Mountford DM. Synthesis 2005; 3279
    • 9b Camp JE, Craig D. Tetrahedron Lett. 2009; 50: 3503
    • 9c Camp JE, Craig D, Funaia K, White AJ. P. Org. Biomol. Chem. 2011; 9: 8000
    • 9d Craig D, Paina F, Smith SC. Chem. Commun. 2008; 3408
    • 9e Craig D, Harvey JW, O’Brien AG, White AJ. P. Org. Biomol. Chem. 2011; 9: 7057
    • 10a Craig D, Gore SJ, Landsell MI, Lewis SE, Mayweg AV. W, White AJ. P. Chem. Commun. 2010; 46: 4991
    • 10b Craig D, Funai K, Gore SJ, Kang A, Mayweg AV. W. Org. Biomol. Chem. 2011; 9: 8000
  • 11 Haufe G, Suzuki S, Yasui H, Terada C, Kitayama T, Shiro M, Shibata N. Angew. Chem. Int. Ed. 2012; 51: 12275