Greener fluorous chemistry: Convenient preparation of new types of ‘CF3-rich’ secondary alkyl mesylates and their use for the synthesis of azides, amines, imidazoles and imidazolium salts

2,2,2-Trifluoroethanol, 1,1,1,3,3,3-hexafluoro-2-propanol, and nonafluoro-tert-butyl alcohol were used as precursors for the preparation of the appropriate bis(polyfluoroalkoxymethyl)carbinols [(RFHOCH2)2CHOH, 1a–c, RFH = (a) CF3CH2, (b) (CF3)2CH, and (c) (CF3)3C] and the corresponding mesylates [(RFHOCH2)2CHOSO2CH3, 2a–c]. This novel design paradigm is introduced to eliminate the persistence and bioaccumulation problems of fluorous chemistry, which are associated with the use of longer linear perfluoroalkyl groups (e.g. Rfn ≥ n-C8F17, n-C7F15). Secondary mesylates 2a,b and the primary tosylate [(CF3)3COCH2CH2OTs, 2d] displayed acceptable reactivity towards azide and imidazole nucleophiles to allow the syntheses of novel fluorous azides, which on hydrogenolysis with H2/Pd-C offered fluorous amines [(RFHOCH2)2CHNH2, 8a,b], and 1-(polyfluoroalkyl)imidazoles (5a,b,d), respectively, while 2c showed no reactivity due to steric hindrance. The reaction of 8a,b with formaline, glyoxal and hydrochloric acid gave symmetrical 1,3-dialkylated imidazolium chlorides (9a,b), while 5a,b,d were effectively alkylated using n-C8F17(CH2)3I, methyl iodide, 2-bromoethanol, and 2d to yield the corresponding 1,3-dialkylimidazolium iodides, bromides, and tosylates (7aa–ec). Some physical properties of new compounds including mp, bp and solubility patterns were also analyzed; and the fluorophilicity values of 1a–c, and 2a–c were experimentally determined by GC and/or 19F NMR spectroscopy.

. 1,3-Bis(polyfluoroalkoxy)propan-2-yl mesylates can be made easily and used as alkylating reagents. Their reaction with sodium azide or imidazole yields the corresponding azides or N-alkylimidazoles, respectively, useful precursors for the synthesis of 1,3-dialkylimidazolium salts.Figure optionsDownload as PowerPoint slideResearch highlights▶ CF3-rich fluorous ponytails were designed to replace perfluoroalkyl groups. ▶ Bis(polyfluoroalkoxymethyl)mesylates were synthesized as alkylating agents. ▶ Alkylating reactions yield fluorous azides and 1-(polyfluoroalkyl)imidazoles. ▶ 1,3-Dialkylimidazolium salts were prepared by alkylating and ring formation. ▶ F-content depending physical data were determined and compared.