The Preparation of Hexafluoroacetone

Abstract

Hexduoroacetone has been obtained by previous workers in the reaction between acetone and elemental fluorine. The reaction was described as complex, difficult to control and hazardous. We have now devised an alternate synthesis which is more convenient for laboratory preparation and which can be extended to large scale operation. The procedure involves many steps, but uses only readily available intermediates and simple, conventional operations.The procedure consists in synthesizing a hexafluorinated derivative of isobutene, preferably (CF&C=CClz, and in oxidizing its double bond to create the ketone function. The synthesis parallels our preparation of trifluoroacetic acid from either CF,CCI=CClz or CF3CCI=CC1CF3.2p3To obtain the desired carbon skeleton and the first CF3 group, CF&(CH3)ClCHzCl was synthesized by two different procedures. In the first sequence, isocrotyl chloride was transformed into CCls(CH3) ClCHzCl by successive chlorinations and dehydrochlorinations, and this pentachlorinated compound was treated with antimony fluoride to transform its CC13 group to a CFa group. In the second sequence, ethyl trifluoroacetate was condensed with methylmagnesium chloride, and the resulting tertiary carbinol was dehydrated to the corresponding olefin, CF3C-(CH3)=CHZ; chlorine was then added to the double bond. Cost considerations favor the first sequence for large quantities, and the second sequence for small preparations.To create the second CF3 group, CF3C(CH3)-CICHzCI was transformed into CF3C(CH3)= CC1z by alternated removals of hydrogen chloride and additions of chlorine; by treatment with antimony fluoride in anhydrous hydrogen fluoride; the olefin was easily transformed into (CF3)z-The olefin most convenient for the oxidation step is (CF,)zC=CClz. It was obtained by chlorination of (CF&CHCH3 to (CF3)2CHCC13 followed by hydrogen chloride removal. The final oxidation was performed with aqueous potassium permanganate, in neutral or acid solutions only on account of the known sensitivity of hexafluoroketone to alkalies. Isolation of the ketone was complicated hy its ability to form a stable hydrate, soluble i n water. 'l'he pure ketone was ultiiiiately obtaiiied by distilling a cuiiceiitrated solution of its hydrate from phosphoric anhydride, and its observed properties proved in agreement with those previously recorded.In the developinent of a practical procedure, CHCH3.(1) Fukuhara and Bigelow, THIS JOURNAL, 63, i 8 8 (1941) (2) Henne, Alderson and Newman, zbid, 61, 918 (1945) (3) H e m e and Trott, ibid., 69, 1820 (1947) HEXAFLUORO ACETONE 3577 CHEMISTRY AT THE OHIO STATE UNIVERSITY]

“Teflon-coated peptides”: Hexafluoroacetone trihydrate as a structure stabilizer for peptides

“…3,4,8 -12 2,2,2-Trifluoroethanol (TFE) has been the most widely used fluoroalcohol additive to aqueous solutions of peptides and proteins. 4,13 -18 We describe in this communication the superior structure-stabilization properties of hexafluoroacetone trihydrate (HFA, a covalent hydrate, of the ketone, a gem diol, hexafluoropropan-2,2diol) [19][20][21] and provide a rationale for the induction of intramolecularly hydrogen-bonded conformations in peptides, in aqueous fluoroalcohol solutions. Figure 1 shows the far-uv CD spectrum of a 21-residue peptide (YHACQKKLLKFEALQQEEGEE; 1), a C-terminal antigenic fragment of the chicken riboflavin carrier protein, 22 in water at pH 2.8.…”

“…fluorosurfactants, as compared to their hydrogenated counterparts. [34][35][36] (2) The enhanced hydrogen bond donating ability of the {OH group, as evidenced by low pKa (6.58) of HFA [19][20][21], H 2 O 15.3] and by the ability of HFA to induce large shifts in the n 0 p* transition of the ketones. 38 In this study, we obtained n 0 p* band positions for acetone in various solvents: HFA 259 nm, H 2 O 262 nm, TFE 266 nm, cyclohexane 278 nm.…”

Behavior of chloro alkenes in sulfur trioxide-sulfuric acid and in fluorosulfonic acid

“…The fluoro analog, 2-methyl-l, 1, l-trifluoro-2-propanol, was prepared from ethyl trifluoroacetate and CH3MgBr as reported. 21 The pmr spectrum consisted of bands at 1.38 and 3.23 in the required ratio of 6:1.…”

Hydrolytische Aktivierung von C-F-Bindungen in der Gasphase durch intrinsisch unreaktive Chrom-Kationen

“…Das Wasser wurde in ein direkt mit dem Gaseinlass‐System des Massenspektrometers verbundenes Halbmikro‐Reagenzglas gegeben und durch zweimaliges Ausfrieren im Vakuum entgast. Hexafluoraceton wurde aus seinem Sesquihydrat (Merck‐Schuchardt, >97 %) in Analogie zu bisherigen Verfahren16–19 durch Umsetzung und zusätzliches Trocknen mit Phosphorpentoxid, P 4 O 10 , freigesetzt.…”