L.V. Kudzma et al. / Journal of Fluorine Chemistry 111 32001) 11±16
15
of these complexes may allow prediction of which kind and
what proportion of amine would work best for a particular
class of substrates.
removed under vacuum into a dry ice-cooled trap, giving
7.55 g of liquid. GCanalysis indicated that this liquid was
28.5% 15 and 64.0% 16, equivalent to 4.83 g 16 ꢀ65% yield
based on consumed starting material). 1H NMR d 5.63
ꢀd, J 51:3 Hz). 19F NMR ꢀH-coupled) d À75.9 ꢀt, 1F,
J 8:2 Hz), À88.3 ꢀt, 2F, J 8:2 Hz), À154.8 ꢀtt, 1F,
J 51:2, 8.2 Hz).
3. Experimental
3.1. General methods and starting materials
3.4. 2-Chloro-1,1,2-trifluoroethyl fluoromethyl
ether 318) [33]
1H NMR spectra were recorded in CDCl3 solvent at either
300 MHz with a Bruker WH-300 instrument, or, for routine
analyses, at 60 MHz with a Hitachi R-1200 instrument;
chemical shifts ꢀd) are reported in ppm down®eld from
the standard tetramethylsilane, d 0. 19F NMR spectra
were recorded in CDCl3 solvent at 282 MHz with a Bruker
WH-300 instrument; chemical shifts are reported in ppm
up®eld from the standard ¯uorotrichloromethane, d 0.
Gas chromatographic analyses were performed on a Hew-
lett-Packard 5890 gas chromatograph ®tted with a packed
Supelco 10% igepalco-880/50% lb-550X on 80/60 Chro-
masorb PAW column with TCD detection.
Detailed preparations for sevo¯urane, 1,2,2,2-tetra¯uor-
oethyl ¯uoromethyl ether ꢀ10) [16], and 1,1,2,3,3,3-hexa-
¯uoropropyl ¯uoromethyl ether ꢀ12) [16] can be found in
[13]. The starting materials 1,2,2,2-tetra¯uoroethyl chloro-
methyl ether ꢀ9) [16], 1,1,2,3,3,3-hexa¯uoropropyl chloro-
methyl ether ꢀ11) [16], 2,2-dichloro-1,1,2-tri¯uoroethyl
chloromethyl ether ꢀ15) [29], 2-chloro-1,1,2-tri¯uoroethyl
chloromethyl ether ꢀ17) [29], 1,1,1,3,3,3-hexa¯uoroisopro-
pyl chloro¯uoromethyl ether ꢀ19) [30], and 1-chloro-2,2,2-
tri¯uoroethyl chloro¯uoromethyl ether ꢀ21) [31] were pre-
pared as previously reported. Chloromethyl ethyl ether ꢀ13),
diisopropylethylamine, triethylamine, triethylamine trihy-
dro¯uoride ꢀtriethylamine trisꢀhydrogen ¯uoride), 4) were
purchased from Aldrich Chemical Co.
A mixture of complex 7 ꢀ17.2 g, 91 mmol), diisopropy-
lethylamine ꢀ23.5 g, 182 mmol), and chloroether 17 ꢀ50.0 g,
273 mmol) was heated at re¯ux under nitrogen for 18 h. The
volatile components were transferred in vacuo to a dry-ice-
cooled receiver, giving 46.4 g liquid. This was washed
with 10% aqueous HCl and water to remove traces of
diisopropylethylamine. Drying over CaCl2 gave 39.8 g
liquid which showed by GCanalysis a 2.0:1.0 mixture of
18 and 17. Fractional distillation using a 2 ft  1=2 in.
vacuum-jacketed column packed with glass beads gave
21.7 g 18 ꢀ66% yield based on consumed starting material),
bp 828Cꢀlit : 83:58C[33]). 1H NMR d 6.14 ꢀdt, 1H
J 48:0, 4.28 Hz), 5.62 ꢀdt, 1H, J 54:2, 3.33 Hz). 19F
NMR ꢀH-decoupled) d À82 ꢀm, 2F), À154.5 ꢀt, 1F,
J 9:0 Hz), À154.8 ꢀbr t, 1F, J 11:6 Hz).
3.5. 1,1,1,3,3,3-Hexafluoroisopropyl difluoromethyl
ether 320) [30]
A mixture of complex 7 ꢀ3.1 ml, 16 mmol), diisopropy-
lethylamine ꢀ5.7 ml, 33 mmol), and chloroether 19 ꢀ10.8 g,
46.0 mmol) was heated at re¯ux under nitrogen for 35 h.
1
Periodic monitoring by H NMR of aliquots dissolved in
CDCl3 indicated the reaction was 77% complete after this
time. Simple distillation gave 7.27 g distillate, bp 52±568C
ꢀlit. bp of pure 20 41:58C[30]). 1H NMR analysis indi-
cated that the distillate was composed of 91% ether 20, 6.5%
starting ether 19, and 2.5% diisopropylethylamine, equiva-
3.2. Fluoromethyl ethyl ether 314) [32]
Diisopropylethylamine ꢀ6.63 ml, 38.1 mmol) was added
to complex 7 under nitrogen, giving a biphasic mixture. With
rapid stirring, chloroether 13 ꢀ5.32 ml, 57.3 mmol) was
added in one portion, giving a mild exotherm. Upon cooling,
the mixture solidi®ed. Simple distillation under nitrogen
gave 2.9 g ꢀ65% yield) 14 as a colorless liquid, bp 368C. 1H
NMR d 5.27 ꢀd, 2H, J 57 Hz), 3.79 ꢀqd, 2H, J 7:2 and
1.2 Hz), 1.29 ꢀt, 3H J 7:2 Hz) [WARNING: Compound
14 is highly unstable to moisture. Upon exposure to the
atmosphere, it decomposes rapidly, producing HF fumes].
1
lent to 6.6 g ꢀ66% yield) of 20. H NMR d 6.44 ꢀt, 1H
J 70:5 Hz), 4.84 ꢀsept, 1H, J 5:66 Hz). 19F NMR ꢀH-
decoupled) d À74.6 ꢀt, 6F, J 4:40 Hz), À85.6 ꢀsept, 2F,
J 4:40 Hz).
3.6. 1-Chloro-2,2,2-trifluoroethyl difluoromethyl
ether 3isoflurane, 22) [29]
A mixture of complex 7 ꢀ7.00 ml, 36.8 mmol), diisopro-
pylethylamine ꢀ12.8 ml, 73.4 mmol), and chloroether 21
ꢀ20.0 g, 99.6 mmol) was heated at re¯ux under nitrogen
for 21 h. Periodic monitoring by 1H NMR of aliquots
dissolved in CDCl3 indicated the reaction was 77% complete
after 4 h. Simple distillation gave 16.4 g distillate, bp 55±
878Cꢀlit. bp of pure 22 48:58C[29]). 1H NMR analysis
indicated that the distillate was composed of 86% ether 22,
and 14% diisopropylethylamine, equivalent to 16.4 g ꢀ77%)
3.3. 2,2-Dichloro-1,1,2-trifluoroethyl fluoromethyl
ether 316) [33]
A mixture of complex 7 ꢀ2.79 g, 14.7 mmol), diisopro-
pylethylamine ꢀ4.07 g, 31.5 mmol), and chloroether 15
ꢀ10.15 g, 46.69 mmol) was heated at re¯ux under nitrogen
for 16 h. After cooling to RT, the volatile component was