New β-amino-α-trifluoromethyl alcohols and their exploration in the synthesis of trifluoromethylated imidazole derivatives

Racemic and enantiomerically pure β-amino-α-trifluoromethyl alcohols were obtained via sequential nucleophilic trifluoromethylation of selected α-imino ketones, derived from arylglyoxals, and subsequent removal of the MeO or Ph(Me)CH substituent, respectively, located at the N-atom. The obtained products, containing a primary amino group, were used for the synthesis of imidazole N-oxides bearing a trifluoromethyl group as a part of the N(1)-alkyl chain. Imidazole N-oxides with an electron-withdrawing ester group at C(4) underwent spontaneous isomerization under the reaction conditions, and the corresponding imidazol-2-ones derivatives were isolated as final products.

Graphical abstractA new approach for synthesis of imidazole derivatives bearing fluorinated hydroxylalkyl group as a substituent at the N(1) atom is described.Figure optionsDownload full-size imageDownload as PowerPoint slideHighlights► Nucleophilic trifluoromethylation of arylgloxal N-substituted monoimines leeds to (β-amino-α-trifluoromethyl)arylethanol derivatives. ► Removal of CH(Me)Ph or OMe groups from the nitrogen atom opens access to primary amino groups. ► In the case of CH(Me)Ph residue attached to the nitrogen atom, synthesis of enantiomerically pure amino alcohols is possible. ► Condensation of β-amino-α-trifluoromethyl-2-arylethanols with H2CO and an appropriate α-hydroxyiminoketone yields N-(3,3,3-trifluoro-2-aryl-2-hydroxypropyl)imidazole derivatives.