Synlett 2010(19): 2971-2972  
DOI: 10.1055/s-0030-1258840
SPOTLIGHT
© Georg Thieme Verlag Stuttgart ˙ New York

2,2,2-Trifluoroethanol

Hartmut Schwertfeger*
Institut für Organische Chemie, Justus-Liebig University, Heinrich-Buff-Ring 58, 35392 Gießen, Germany
e-Mail: [email protected];

Further Information

Publication History

Publication Date:
22 October 2010 (online)

Biographical Sketches

Hartmut Schwertfeger was born in 1979 in Lahn-Gießen, Germany. He studied chemistry at the Justus-Liebig University Gießen (2001-2005) and received his diploma in September 2006. During his diploma thesis in the group of Professor P. R. Schreiner he worked on the preparation of functionalized diamondoid derivatives. He continued his work on the selective functionalizations of diamondoids in the same group and received his doctorate in April 2010.

Introduction

2,2,2-Trifluoroethanol (TFE) is one of the most common used fluorinated alcohols that is available on large commercial scale. In contrast to its non-fluorinated analogue, TFE has a lower boiling point (74 ˚C) and is more acidic (pKa 12.4). [¹] Due to its low boiling point TFE can easily be removed from reaction mixtures by destillation. TFE can be prepared by reduction of trifluoroacetamide [²] or trifluoroacetic acid [³] with H2 and various catalysts. Another possibility is the treatment of trifluoroacetyl chloride [4] and n-butyl trifluoroacetate [5] using LiAlH4 (Scheme  [¹] ). Owing to its unique properties TFE has been used in a variety of reactions as a solvent, cosolvent or additive, [¹] but it can also be utilized as a reagent for the introduction of a fluorine moiety.

Scheme 1 Preparation of 2,2,2-trifluoroethanol

Abstracts

(A) TFE was used as a recyclable solvent for the one-pot, three component coupling of aldehydes or ketones, amines, and trimethylsilyl cyanide or trimethyl phosphite to give α-amino phosphonates or α-amino nitriles. [6]

(B) Primary alcohols were converted into their corresponding 2,2,2-trifluoroethyl esters with iodine and K2CO3 in TFE. In this reaction TFE acts as reagent and solvent. [7]

(C) TFE can also be used as a simple starting compound to generate precursors for fluorinated sugar structures. Thereby, TFE is firstly converted into an allyl ether that is further transformed into cyclohexene diols. [8]

(D) The difluorovinylation of arylboronic acids was achieved via the Suzuki-Miyaura cross-coupling. In this reaction, TFE was transferred into the 2,2-difluorovinyl tosylate, which was then utilized as a reagent in the coupling reaction. [9]

(E) The hydroalkoxylation of hexafluoropropene with TFE in the presence of a catalytic system consisting of a potassium salt and an ionic liquid leads to the formation of CF3CHFCF2OCH2CF3. This compound is one of the third generation chlorofluorocarbons (CFC) alternatives. [¹0]

(F) Hantzsch 1,4-dihydropyridines (and also polyhydroquinolines) can be prepared in high yields by utilizing TFE as solvent. After the reation the solvent is distilled off and can be reused in further reactions. [¹¹]

(G) Aliphatic and aromatic epoxides react with indoles and pyrroles in TFE without the use of a catalyst. In this reaction the ring opening is electrophilically assisted by TFE. The examples shown have high stereoselectivites (>99% ee) indicating an SN2-type process. [¹²]

(H) Quinolinones can be obtained by oxidation of methoxyamides utilizing a hypervalent iodine reagent. This reagent is prepared electrochemically from iodobenzene and TFE. [¹³]

(I) The monoprotection (desymmetrization) of diamondoid, benzy­lic, and ethynyl diols has been achieved using TFE under acidic conditions. The obtained diamondoid monoethers can further be converted into unequally disubstituted diamondoid derivatives, such as amino acids or amino alcohols. [¹4]

    References

  • 1a Bégué J.-P. Bonnet-Delpon D. Crousse B. Synlett  2004,  18 
  • 1b Shuklov IA. Dubrovina NV. Börner A. Synthesis  2007,  2925 
  • 2 Gilman H. Jones RG. J. Am. Chem. Soc.  1948,  70:  1281 
  • 3 Lee D. Kim H. Kang M. Kim JM. Lee I. Bull. Korean Chem. Soc.  2007,  28:  2034 
  • 4 Henne AL. Alm RM. Smook M. J. Am. Chem. Soc.  1948,  70:  1968 
  • 5 Campbell KN. Knobloch JO. Campbell BK. J. Am. Chem. Soc.  1950,  72:  4380 
  • 6 Heydari A. Khaksar S. Tajbakhsh M. Tetrahedron Lett.  2009,  50:  77 
  • 7 Mori N. Togo H. Synlett  2004,  880 
  • 8 Audouard C. Fawcett J. Griffith GA. Krourdan E. Miah A. Percy JM. Yang H. Org. Lett.  2004,  6:  4269 
  • 9 Gøgsig TM. Søbjerg LS. Lindhardt AT. Jensen KL. Skrydstrup T. J. Org. Chem.  2008,  73:  3404 
  • 10 Kang JE. Lee JS. Kim DS. Lee SD. Lee H. Kim HS. Cheong M. J. Catal.  2009,  262:  177 
  • 11 Heydari A. Khaksar S. Tajbakhsh M. Bijanzadeh HR. J. Fluorine Chem.  2009,  130:  609 
  • 12 Westermaier M. Mayr H. Chem. Eur. J.  2008,  14:  1638 
  • 13a Amano Y. Nishiyama S. Tetrahedron Lett.  2006,  47:  6505 
  • 13b Amano Y. Inoue K. Nishiyama S. Synlett  2008,  134 
  • 14 Schwertfeger H. Würtele C. Serafin M. Hausmann H. Carlson RMK. Dahl JEP. Schreiner PR. J. Org. Chem.  2008,  73:  7789 

    References

  • 1a Bégué J.-P. Bonnet-Delpon D. Crousse B. Synlett  2004,  18 
  • 1b Shuklov IA. Dubrovina NV. Börner A. Synthesis  2007,  2925 
  • 2 Gilman H. Jones RG. J. Am. Chem. Soc.  1948,  70:  1281 
  • 3 Lee D. Kim H. Kang M. Kim JM. Lee I. Bull. Korean Chem. Soc.  2007,  28:  2034 
  • 4 Henne AL. Alm RM. Smook M. J. Am. Chem. Soc.  1948,  70:  1968 
  • 5 Campbell KN. Knobloch JO. Campbell BK. J. Am. Chem. Soc.  1950,  72:  4380 
  • 6 Heydari A. Khaksar S. Tajbakhsh M. Tetrahedron Lett.  2009,  50:  77 
  • 7 Mori N. Togo H. Synlett  2004,  880 
  • 8 Audouard C. Fawcett J. Griffith GA. Krourdan E. Miah A. Percy JM. Yang H. Org. Lett.  2004,  6:  4269 
  • 9 Gøgsig TM. Søbjerg LS. Lindhardt AT. Jensen KL. Skrydstrup T. J. Org. Chem.  2008,  73:  3404 
  • 10 Kang JE. Lee JS. Kim DS. Lee SD. Lee H. Kim HS. Cheong M. J. Catal.  2009,  262:  177 
  • 11 Heydari A. Khaksar S. Tajbakhsh M. Bijanzadeh HR. J. Fluorine Chem.  2009,  130:  609 
  • 12 Westermaier M. Mayr H. Chem. Eur. J.  2008,  14:  1638 
  • 13a Amano Y. Nishiyama S. Tetrahedron Lett.  2006,  47:  6505 
  • 13b Amano Y. Inoue K. Nishiyama S. Synlett  2008,  134 
  • 14 Schwertfeger H. Würtele C. Serafin M. Hausmann H. Carlson RMK. Dahl JEP. Schreiner PR. J. Org. Chem.  2008,  73:  7789 

Scheme 1 Preparation of 2,2,2-trifluoroethanol