4
K. Ramig et al. / Journal of Fluorine Chemistry 94 (1999) 1±5
in the latter case, lower selectivity resulted because the
¯uoride source decomposed after ¯uoride donation to give
an acid ¯uoride, which caused an appreciable amount of
¯uorination itself. In both cases, the by-products from the
¯uoride source were either highly volatile or water-reactive,
which simpli®ed puri®cation after aqueous work-up. The
new ¯uorination system was applied to an improved synth-
esis of the anesthetic compound 2,2,2-trichloro-1,1-di¯uoro-
ethyl methyl ether (2).
8 were easily removed by distillation through a short
Vigreux column to give pure 2, bp 568C/80 mmHg (lit.
1
bp 468C/46 mmHg [2]). 2: H NMR ꢀ 3.77 ppm (s); 19F
NMR ꢀ 89.5 ppm (s); 13C NMR ꢀ 52.7 (t, J6.2 Hz), 94.0
(t, J44 Hz) 120 (t, J271 Hz) ppm.
4.4. Dichloroacetyl fluoride (8)
SbCl5 (2.20 g, 7.36 mmol) was added dropwise to meth-
oxy¯urane (6) (56.7 g, 344 mmol) at r.t. under N2. After
heating at 408C for 1 h, additional SbCl5 (2.57 g,
8.59 mmol) was added and the mixture was heated for an
additional 45 min to complete the reaction. The mixture was
distilled under N2 using a short Vigreux column, giving
31.4 g (70% yield) of dichloroacetyl ¯uoride (8) as a clear
liquid, bp 688C (lit. bp 708C [10]). 8: 1H NMR ꢀ 6.09 ppm
(d, J2.6 Hz); 19F NMR ꢀ 21.1 ppm (s).
4. Experimental
4.1. General
Antimony pentachloride was obtained from Aldrich and
was of 99.99% purity. All reactions were run under an
atmosphere of N2. Boiling points are uncorrected. 1H NMR
spectra (TMS reference) were recorded at 300 MHz, 19F
NMR spectra (CFCl3 reference, proton decoupled) at
282 MHz, and 13C NMR spectra (TMS reference, proton
decoupled) at 75 MHz.
4.5. Chlorofluoroacetyl fluoride (21)
SbCl5 (5.00 g, 16.9 mmol) was added dropwise to 2-
chloro-1,1,2-tri¯uoroethyl methyl ether (9) (50.0 g,
337 mmol) at r.t. under N2 using a condenser kept at
58C. After heating at 25±308C for 30 min, distillation
gave 28.1 g (73% yield) of chloro¯uoroacetyl ¯uoride (21)
4.2. 1,2,2,2-Tetrachloro-1-fluoroethyl methyl ether (1)
1
Methoxy¯urane (6) (500 g, 3.03 mol) was heated at re¯ux
under N2 over KOH pellets (175 g (85%), 2.66 mol) over-
night. Distillation to dryness under N2 gave a mixture of
water and crude product. The crude product was dried over
KOH, giving 424 g of a mixture of methoxy¯urane (6) and
2,2-dichloro-1-¯uorovinyl methyl ether (7) which was car-
ried into the chlorination without further puri®cation. 7: lit.
bp 1018C [2], 1H NMR ꢀ 3.81 ppm (s), 19F NMR ꢀ
90.7 ppm (s).
A 413 g portion of the mixture was cooled to 408C and
chlorine was bubbled through until uptake ceased. At this
point, the solution was a 50:50 mixture of 1 and methoxy-
¯urane. Fractional distillation in vacuo gave 171 g of
1,2,2,2-tetrachloro-1-¯uoroethyl methyl ether (1), bp 58±
618C/25 mmHg (lit. bp 578C/18 mmHg [2]). Overall
yield42%, based on consumed methoxy¯urane. 1: 1H
NMR ꢀ 3.84 ppm (s); 19F NMR ꢀ 69.5 ppm (br s).
as a clear liquid, bp 32±338C (lit. bp 34±448C [7]). 21: H
NMR ꢀ 6.45 ppm (d, J49 Hz); 19F NMR ꢀ 20.0 (d,
J22 Hz, 1 F), 148 (d, J22 Hz, 1 H) ppm.
4.6. Fluorination of trichloromethyl 2,2,2-trifluoro-1-
(trifluoromethyl)ethyl ether (18) with dichloroacetyl
fluoride (8)
SbCl5 (1.01 g, 3.38 mmol) was added dropwise to a
stirred solution of trichloromethyl 2,2,2-tri¯uoro-1-(tri-
¯uoromethyl)ethyl ether (18) (23.5 g, 82.5 mmol) and
dichloroacetyl ¯uoride (8) (10.8 g, 82.5 mmol) at r.t. under
N2. After 1.5 h, the mixture was cooled to 38C and ice-cold
H2O (20 ml) was added in portions with rapid stirring. After
the exotherm had subsided, the organic layer was washed
with dilute Na2CO3 solution (10 ml) and dried over CaCl2.
Isolated was 21.0 g liquid which by NMR contained 95%
dichloro¯uoromethyl 2,2,2-tri¯uoro-1-(tri¯uoromethyl)-
ethyl ether (19) (yield91% based on 8); the remainder
was 18.
4.3. 2,2,2-Trichloro-1,1-difluoroethyl methyl ether (2)
SbCl5 (3.36 g, 11.2 mmol) was added dropwise to a
stirred solution of 1,2,2,2-tetrachloro-1-¯uoroethyl methyl
ether (1) (80.9 g, 375 mmol) and methoxy¯urane (6)
(61.9 g, 375 mmol) at r.t. under N2. Vigorous gas evolution
and an exotherm to 408C resulted. After 50 min, the mixture
was cooled to 08C and ice-cold H2O (70 ml) was added
dropwise. Vigorous gas evolution [CAUTION: probably
HF] and an exotherm to 458C resulted. After thorough
mixing, the lower organic phase was dried over CaCl2,
giving 65.1 g clear liquid which by NMR contained
55.3 g (74%) of 2. The contaminants methyl chloride and
4.7. Fluorination of trichloromethyl 2,2,2-trifluoro-1-
(trifluoromethyl)ethyl ether (18) with
chlorfluoroacetyl fluoride (21)
SbCl5 (1.57 g, 5.25 mmol) was added dropwise to a
stirred solution of trichloromethyl 2,2,2-tri¯uoro-1-(tri-
¯uoromethyl)ethyl ether (18) (15.0 g, 52.5 mmol) and
chloro¯uoroacetyl ¯uoride (21) (6.00 g, 52.5 mmol) at r.t.
under N2. The mixture was heated at 608C for 1 h. Aqueous
work-up as before gave 10.6 crude product. NMR analysis