Direct Conversion of Carboxylic Acids to
Trifluoromethyl Ketones

A recent publication from workers at Boehringer-Ingelheim* describes a method for the direct conversion of primary and secondary carboxylic acids to trifluoromethyl ketones by reaction with trifluoroacetic anhydride (TFAA) and pyridine in toluene. Tertiary carboxylic acids are not mentioned in the report, but since a pyridinium enolate is proposed as an intermediate, it seems that the presence of at least one α–proton is necessary and so tertiary carboxylic acids will not react.

In a typical reaction the carboxylic acid is reacted with 4.5 equivalents of TFAA and 6 equivalents of pyridine in toluene at 60 oC for 8 hours (for primary carboxylic acids) or 75-100 oC for 24-48 hours for secondary carboxylic acids. Yields of 55-82% are achieved with primary carboxylic acids, and 41-66% for secondary carboxylic acids. Trevor Laird

*J.T. Reeves et al., Tetrahedron Letters 2007, 48, 189-192


 

 Trevor Laird