<i>N</i>,<i>N</i>‐Bis(trifluoromethyl)aminoacetonitrile: A Versatile Building Block for the Introduction of the Bis(trifluoromethyl)amino Group
N,N-Bis(trifluoromethyl)aminoacetonitrile (CF<sub>3</sub>)<sub>2</sub>NCH<sub>2</sub>CN (1) that is accessible via a simple single-step protocol is established as a building block for the introduction of the (CF<sub>3</sub>)<sub>2</sub>N group. The two reaction sites of 1, the methylene unit and the nitrile (cyano) group, provide access to different organic substance classes. This includes alkenes via Knoevenagel condensations, and N-heterocycles and acid derivatives obtained by addition reactions to the nitrile unit. These new (CF<sub>3</sub>)<sub>2</sub>N derivatives are potential building blocks containing the bis(trifluoromethyl)amino group. Deprotonation of 1 at the methylene group highlights the electron-withdrawing nature of the (CF<sub>3</sub>)<sub>2</sub>N group. The {(CF<sub>3</sub>)<sub>2</sub>NCHCN}<sup>-</sup> anion (1<sup>-</sup>) is characterized by NMR spectroscopy and its reaction with [Ph<sub>3</sub>PAuCl] results in [Ph<sub>3</sub>PAuCH{N(CF<sub>3</sub>)<sub>2</sub>}(CN)] (Au1) and [(Ph<sub>3</sub>PAu)<sub>2</sub>C{N(CF<sub>3</sub>)<sub>2</sub>}(CN)] (Au<sub>2</sub>1). Crystal structure analysis of (CF<sub>3</sub>)<sub>2</sub>NCH<sub>2</sub>CN (1), Au<sub>2</sub>1, and almost all alkenes, N-heterocycles, and acid derivatives with a (CF<sub>3</sub>)<sub>2</sub>N group combined with spectroscopic data and results from DFT calculations provide insight into properties of the highly fluorinated (CF<sub>3</sub>)<sub>2</sub>N substituent. Especially the ability of the amino nitrogen atom to participate in weak hydrogen bonding, albeit its low basicity, is of relevance.
Authors
- Michael Schulte
- Christoph Breitenstein
- Holger Braunschweig (ORCID: https://orcid.org/0000-0001-9264-1726)
- Leon N. Schneider
- Younes K. J. Bejaoui
- Kristina A. M. Maibom
- Maik Finze (ORCID: https://orcid.org/0000-0002-6098-7148)
- Carl Deutsch
- Sabine Lorenzen
- Krzysztof Radacki (ORCID: https://orcid.org/0000-0003-3088-6327)
- Thomas Fuchß (ORCID: https://orcid.org/0000-0002-1203-7180)
- Tanja Knuplez (ORCID: https://orcid.org/0009-0005-3228-0064)
- Nikolai V. Ignat’ev
- Min Shan
- Johannes Gierling
Institutions
- Merck KGaA, Darmstadt (Germany) (DE)
- University of Würzburg (DE)
- NBE Therapeutics (Switzerland) (CH)
- Heinrich Heine University Düsseldorf (DE)
Publication Details
- Journal
- Chemistry - A European Journal
- Published
- 2025-06-02
- DOI
- https://doi.org/10.1002/chem.202501550
- Citations
- 2
- Primary Topic
- Fluorine in Organic Chemistry
- Type
- article
- Field-Weighted Citation Impact
- 1.58