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Updated: Oct 3, 2025

Protocol for the Synthesis of Ortho-trifluoromethoxylated Aniline Derivatives
Published on: January 19, 2016
Experimental and computational study of BF3-catalyzed transformations of ortho-(pivaloylaminomethyl)benzaldehydes: an
Györgyi Koványi-Lax1, Csilla Hargitai1, Péter Ábrányi-Balogh2
1Directorate of Drug Substance Development, Egis Pharmaceuticals Plc., P.O. Box 100, H-1475 Budapest, Hungary. volk.balazs@egis.hu.
Abstract:
Previously, we have studied the trifluoroacetic acid (TFA)-catalyzed rearrangements of unsubstituted and alkoxy-substituted ortho-(pivaloylaminomethyl)benzaldehydes and revealed the formation of rearranged, regioisomeric aldehydes along with dimer-like products ("TFA dimers"). In the present study, related reactions of ortho-(pivaloylaminomethyl)benzaldehydes are described with the difference that boron trifluoride diethyl etherate (BF3·OEt2) is used as the catalyst. Although in these reactions the formation of the same "TFA dimers" can be observed after a couple of hours reaction time, during further stirring these are transformed into a new dimer-like keto compound ("BF3 dimer") that gradually becomes the main product. Apart from this, an oxoindene-type by-product is also formed. The new products are characterized by detailed NMR studies and two of them also by single-crystal X-ray diffraction. DFT calculations support the mechanism proposed for the transformations and explain the differences observed in the product distribution.
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