2-Trifluoromethoxyethyl triflate: A versatile trifluoromethoxyethyl carrier

Full text of DOI:10.1021/jo005701t

J . Org. Chem. 2001, 66, 1061-1063
1061
Sch em e 1
2-Tr iflu or om eth oxyeth yl Tr ifla te: A
Ver sa tile Tr iflu or om eth oxyeth yl Ca r r ier
J ean-Claude Blazejewski,* Elsa Anselmi, and
Claude Wakselman
SIRCOB, ESA CNRS 8086, Universite´ de Versailles,
45 Avenue des Etats-Unis, 78035 Versailles, France
jcblaz@chimie.uvsq.fr
Received October 27, 2000
In tr od u ction
On the basis of its electronic properties, which are close
to those of a chlorine or a fluorine atom,1 the trifluoro-
methoxy group has been referred to as a super-2 or a
pseudo-halogen.3 On the other hand, the fluorination of
carbon adjacent to oxygen atoms increases lipophilicity
as shown by the high value of the OCF3 hydrophobic
substituent parameter.4 Molecules bearing this group
should be more able to traverse lipid membranes than
their non fluorinated analogues. Unlike aromatic tri-
fluoromethyl ethers,5 there are few examples of aliphatic
trifluoromethyl ethers;6 mainly because there is no
general direct method for the introduction of the OCF3
unit in organic molecules.7 We here report the prepara-
tion of 2-trifluoromethoxyethyl triflate 3 from ethylene
glycol derivatives 1a -c and its use as a useful aliphatic
trifluoromethyl ether carrier for the preparation of
substituted aliphatic trifluoromethyl ethers 6a -f by its
ready reaction with various nucleophiles.
function could survive the fluorination conditions while
enabling further chemical transformations.
For our purpose, xanthate esters of ethylene glycol
derivatives 1a -c were readily obtained using minor
variations of the standard phase transfer procedure.11
Fluorination of the xanthates 1a -c using the HF-
pyridine, DBH method (Scheme 1) proceeds uneventfully
to give the corresponding trifluoromethyl ethers 2a -c
in good yields.
To obtain other functional trifluoromethyl ethers from
compounds 2a -c, the nonfluorinated group has to be
transformed selectively. Various methods are described
in the literature for the cleavage of simple ethers. THF,
for example, is known to be cleaved symmetrically by
trifluoromethanesulfonic anhydride ((CF3SO2)2O) to give
1,4-butaneditriflate.12 It has been claimed that the same
behavior is observed with diethyl ether.13
In the event, however, only trace amounts of triflate 3
were formed during attempted cleavage of the bis-ether
2a with (CF3SO2)2O under strictly anhydrous conditions
(sealed tube, 60 °C, 4 days). Under more forcing condi-
tions (80 °C reflux, 2 days) and using an excess of (CF3-
SO2)2O, the main product formed was the bis triflate 4.14
We suspected that in this case trace amounts of trifluo-
romethanesulfonic acid may have catalyzed the reaction.
Trifluoromethanesulfonic acid itself is also known to
cleave diethyl ether to give ethylene and ethyl triflate.15
Attempted cleavage of the ether 2a with CF3SO3H alone
(60 °C, 3 days) gave an incomplete reaction (50% conver-
sion) and resulted in a complex mixture of fluorinated
products. After some trials, it turned out that when ether
2a was held at 60 °C for 2 days with a mixture comprising
(CF3SO2)2O (4 equiv) and CF3SO3H (0.1 equiv) a clean
reaction was observed leading to triflate 3 in 50% isolated
yield.16 These experimental conditions were then applied
to ethers 2b and 2c giving triflate 3 in 27 and 73%
isolated yield, respectively. The lower yield encountered
Resu lts a n d Discu ssion
Recent advances in the fluorodesulfurization reaction8
enabled the preparation of aromatic as well as aliphatic
trifluoromethyl ethers by treatment of dithiocarbonates
(xanthate esters) with 1,3-dibromo-5,5-dimethylhydan-
toin (DBH) in an HF-pyridine medium.9 This transfor-
mation may be interpreted as involving successive bro-
monium formation with sulfur atoms followed by nucleo-
philic introduction of fluorine substituents. To our knowl-
edge, no functional fluorinated ether has been prepared
using this methodology. Our own work in this area has
shown that a functional group (e.g., ester) close to the
xanthate ester does interfere (or even participate) with
the fluorination process.10 We thought that an ether
(1) Olah, G. A.; Yamamoto, T.; Hashimoto, T.; Shih, J . G.; Trivedi,
N.; Singh, B. P.; Piteau, M.; Olah, J . A. J . Am. Chem. Soc. 1987, 109,
3708.
(2) Sheppard, W. A. J . Am. Chem. Soc. 1962, 85, 1314.
(3) Haas, A. Adv. Inorg. Chem. Radio Chem. 1984, 28, 167.
(4) Smart, B. E. In Chemistry of Organic Fluorine Compounds II;
Hudlicky´, M., Pavlath, A. E., Eds.; ACS Monograph 187; American
Chemical Society: Washington, DC, 1997; p 986.
(5) Clarck, J . H.; Wails, D.; Bastock, T. W. Aromatic fluorination;
CRC Press: Boca Raton, 1996; Chapter 7.
(6) Ben-David, I.; Rechavi, D.; Mishani, E.; Rozen, S. J . Fluorine
Chem. 1999, 97, 75.
(7) McClinton, M. A.; McClinton, D. A. Tetrahedron 1992, 48, 6555.
(8) Kollonitsch, J .; Marburg, S.; Perkins, L. M. J . Org. Chem. 1976,
41, 3107. See also: Sondej, S. C.; Katzenellenbogen, J . A. J . Org. Chem.
1986, 51, 3508.
(11) Lee, A. W. M.; Chan, W. H., Wong, H. C.; Wong, M. S. Synth.
Commun. 1989, 19, 547.
(12) Beard, C. D.; Baum, K.; Grakauskas, V. J . Org. Chem. 1973,
38, 3673.
(13) Forbus, T. R., J r.; Taylor, S. L.; Martin, J . C. J . Org. Chem.
1987, 52, 4156. This specific example does not appear, however, in
the cited publication (ref 12).
(14) Katsuhara, Y.; Desmarteau, D. D. J . Fluorine Chem. 1980, 16,
257.
(9) Kanie, K.; Tanaka, Y.; Suzuki, K.; Kuroboshi, M.; Hiyama, T.
Bull. Chem. Soc. J pn. 2000, 73, 471.
(10) Lequesne, C. Thesis, University of Versailles, 1997.
(15) Gramstad, T.; Haszeldine, R. N. J . Org. Chem. 1957, 22, 9.
(16) Based on the expectation that cleavage of 2a should give two
molecules of 3.
10.1021/jo005701t CCC: $20.00 © 2001 American Chemical Society
Published on Web 01/09/2001

1062 J . Org. Chem., Vol. 66, No. 3, 2001
Notes
After removal of the solvents, the solid residue was eluted on a
silica gel column using first 20% CH2Cl2/pentane as eluent to
remove less polar impurities (mainly dimethyl trithiocarbonate).
Further elution with CH2Cl2 gave 35.1 g (87% yield) of [MeSC-
(S)O(CH2)2]2O as pale yellow crystals: mp 62.5-62.9 °C; 1H
NMR (CDCl3) δ 4.6 (m, 4 H), 3.8 (m, 4 H), 2.5 (s, 6 H); 13C NMR
Sch em e 2
(CDCl3) δ 215.8, 72.5, 68.7, 19.0; FTIR (CCl4) 1197, 1079 cm-1
;
CIMS (NH3) m/z 304 (M + NH4+, 5), 135 (75), 70 (100). Anal.
Calcd for C8H14O3S4: C, 33.54; H, 4.93; O, 16.76; S, 44.78.
Found: C, 33.59; H, 4.91; O, 16.81; S, 44.75.
P r ep a r a tion of EtO(CH2)2O(CH2)2OC(S)SMe (1b). Simi-
larly, 1b was prepared by the general procedure from 5.0 g (37.3
mmol) of diethyleneglycol monoethyl ether, 0.5 g (1.4 mmol) of
nBu4NHSO4, 40 mL of 50% NaOH, 40 mL of CS2, and 6.4 g (45
mmol) of MeI. The reaction mixture was purified as described
above and gave 5.9 g (71% yield) of EtO(CH2)2O(CH2)2OC(S)-
SMe as a yellow oil: 1H NMR (CDCl3) δ 4.11 (t, J ) 4.9 Hz, 2
H), 3.73 (t, J ) 4.9 Hz, 2 H), 3.68 (m, 2 H); 3.61 (m, 2 H), 3.54
(q, J ) 7.0 Hz, 2 H), 2.54 (s, 3 H), 1.22 (t, J ) 7.0 Hz, 3 H); 13C
NMR (CDCl3) δ 215.8, 72.6, 70.7, 69.7, 68.4, 66.5, 18.9, 15.0;
FTIR (CCl4) 1170, 1090 cm-1; LRMS m/z 224 (M+, 1), 116 (45),
72 (100). Anal. Calcd for C8H16S2O3: C, 42.83; H, 7.19; S, 28.59.
Found: C, 42.73; H, 7.18; S, 28.46.
in the cleavage of ether 2b was not unexpected because
of the various protonation sites possible. In this specific
case we also isolated triflate 5.
Triflate 3 proved to be a valuable intermediate for the
formation of substituted trifluoromethyl ethers. It thus
reacted readily with various common nucleophiles under
mild conditions (THF, rt) to give the products 6a -e in
good yields (Scheme 2). Further deprotection of the
phthalimide derivative 6e using hydrazine hydrate17
afforded the potentialy useful amine 6f, isolated as its
hydrochloride salt in 70% yield.
P r ep a r a tion of C5H11O(CH2)2OC(S)SMe (1c). Similarly 1c
was prepared by the general procedure from 4.6 g (35 mmol) of
ethyleneglycol monopentyl ether, 0.5 g (1.4 mmol) of nBu4NHSO4,
40 mL of 50% NaOH, 40 mL of CS2, and 6.4 g (45 mmol) of MeI.
The reaction mixture was purified as described above and gave
7.0 g (91% yield) of C5H11O(CH2)2OC(S)SMe as a yellow oil: bp
252-254 °C (Siwoloboff); 1H NMR (CDCl3) δ 4.73 (m, 2H), 3.77
(m, 2H), 3.46 (t, J ) 6.7 Hz, 2H), 2.57 (s, 3 H), 1.59 (m, 2 H),
1.34 (m, 4 H), 0.9 (m, 3 H); 13C NMR (CDCl3) δ 216.0, 72.8, 71.5,
67.9, 29.2, 28.1, 22.4, 19.0, 14.0; FTIR (CCl4) 1192, 1095 cm-1
;
LRMS m/z 223 (M+ + 1, 1), 114 (63), 99 (100). Anal. Calcd for
C9H18O2S2: C, 48.61; H, 8.16. Found: C, 48.49; H, 8.30.
Con clu sion s
It appears that ether substituents are compatible with
the experimental conditions of the fluorodesulfurization
reaction of alkyl dithiocarbonates. Starting from the
xanthate ester 1a , it is possible to obtain by this way the
hemifluorinated glyme 2a . A regioselective cleavage of
the non fluorinated ether group allows the preparation
of the trifluoromethoxy substituted triflate 3 from eth-
ylene glycol derivatives. Its ready reaction with nucleo-
philes open the way to the easy introduction of the
2-trifluoromethoxyethyl moiety into organic molecules.
This substituent should increase the lipophilicity of the
products and consequently their bioavailability.
Gen er a l P r oced u r e for th e P r ep a r a tion of Tr iflu or o-
m eth yl Eth er s As Descr ibed by th e P r ep a r a tion of [CF 3O-
(CH2)2]2O (2a ). A two-necked 500 mL round-bottomed flask
equipped with a magnetic stirbar, a septum port, and a reflux
condenser connected to a silica gel guard was charged with 60.0
g (210 mmol) of 1,3-dibromo-5,5-dimethylhydantoin (DBH) and
300 mLof CH2Cl2, The flask was immersed in a dry ice/acetone
cooling bath and the HF/pyridine complex (50 mL) was added
via a polyethylene syringe followed by 10.0 g (35 mmol) of the
bis-xanthate 1a . The cooling bath was removed and the reaction
mixture was allowed to reach rt over 2 h. The mixture was
poured into 500 mL of ice water, diluted with 100 mL of CH2-
Cl2, and saturated with NaCl. The organic layer was removed,
and the aqueous phase was extracted with 3 × 200 mL of CH2-
Cl2. The organic layers were pooled and washed successively
with 250 mL of a cold 37% NaHSO3 solution and then with 2 ×
250 mL of cold brine. After drying (MgSO4) and removal of the
solvents, short-path distillation of the residue (0.01 mmHg) to
a cold (-78 °C) trap gave 6.7 g (79% yield) of [CF3O(CH2)2]2O
as a colorless oil: bp 132-134 °C (Siwoloboff); 1H NMR (CDCl3)
δ 4.0 (m, 4 H), 3.7 (m, 4 H); 13C NMR (CDCl3) δ 121.6 (q, J )
255 Hz), 66.5 (q, J ) 3.3 Hz), 68.8 (s); 19F NMR (CDCl3) δ -61,5;
LRMS m/z 241 (M+ - H, 1), 143 (60), 113 (86), 69 (100). Anal.
Calcd for C6H8O3F6: C, 29.76; H, 3.33. Found: C, 29.88; H, 3.31.
P r ep a r a tion of CF 3O(CH2)2O(CH2)2OEt (2b). Similarly, 2b
was prepared by the general procedure from 5.0 g (22.3 mmol)
of xanthate 1b, 32.0 g (112 mmol) of DBH, and 37 mL of HF/
pyridine complex in 150 mL of CH2Cl2. Column chromatography
of the crude reaction mixture (SiO2, CH2Cl2) gave 3.13 g (70%
yield) of CF3O(CH2)2O(CH2)2OEt as a colorless oil: bp 152-154
°C (Siwoloboff); 1H NMR (CDCl3) δ 4.11 (m, 2 H), 3.75 (m, 2 H),
3.67 (m, 2 H), 3.61 (m, 2 H), 3.54 (q, J ) 7 Hz, 2 H), 1.22 (t, J )
7 Hz, 3 H); 13C NMR (CDCl3) δ 121.6 (q, J ) 254 Hz), 70.9, 69.7,
68.6, 66.6, 66.5 (q, J ) 3.3 Hz), 15.0; 19F NMR (CDCl3) δ -61.4;
LRMS m/z 202 (M+, 1), 73 (71), 69 (91), 59 (100). Anal. Calcd
for C7H13O3F3: C, 41.59; H, 6.48. Found: C, 41.56; H, 6.64.
P r ep a r a tion of CF 3O(CH2)2OC5H11 (2c). Similarly, 2c was
prepared by the general procedure from 5.0 g (22.5 mmol) of
xanthate 1c, 19.3 g (67.6 mmol) of DBH, and 37 mL of
HF/pyridine complex in 150 mL of CH2Cl2. Column chromatog-
raphy of the crude reaction mixture (SiO2, 30% CH2Cl2/pentane)
gave 3.1 g (69% yield) of CF3O(CH2)2OC5H11 as a colorless oil:
Exp er im en ta l Section
Gen er a l Meth od s. NMR spectra were recorded as CDCl3
solutions. The reported coupling constants and chemicals shifts
were based on a first-order analysis. Internal reference was the
residual peak of CHCl3 (δ 7.27) for 1H (300 MHz), central peak
of CDCl3 (δ 77) for 13C (75 MHz) spectra and internal CFCl3 (0
ppm) for 19F (282 MHz) NMR spectra. Elemental analyses were
obtained at ICSN, Gif-sur-Yvette, France. The hydrogen fluoride-
pyridine complex used was purchased from Aldrich and contains
ca. 70% HF.
Gen er a l P r oced u r e for th e P r ep a r a tion of Xa n th a tes As
Descr ibed by th e P r ep a r a tion of [MeSC(S)O(CH2)2]2O (1a ).
A two-necked
1 L round-bottomed flask equipped with a
magnetic stirbar and a reflux condenser was charged with 15.0
g of diethyleneglycol (140 mmol) and 3.0 g of tetrabutylammo-
nium sulfate (8.8 mmol). A 50% solution of sodium hydroxide
(282 mL) was added via a dropping funnel. After the mixture
was stirred for 10 min, CS2 (282 mL) was added dropwise,
followed by 43.7 g of iodomethane (310 mmol). The mixture was
stirred for 4 h at room temperature. Water (40 mL) was added.
The organic layer was removed, and the aqueous phase was
extracted with CH2Cl2 (3 × 30 mL). The pooled organic layers
were washed with brine (2 × 20 mL) and dried over MgSO4.
(17) Sheehan, J . C.; Bolhofer, W. A. J . Am. Chem. Soc. 1950, 72,
2786.

Notes
J . Org. Chem., Vol. 66, No. 3, 2001 1063
bp 142-144 °C (Siwoloboff); 1H NMR (CDCl3) δ 4.07 (t, J ) 4.7
Hz, 2 H), 3.64 (t, J ) 4.7 Hz, 2 H), 3.47 (t, J ) 6.6 Hz, 2 H), 1.59
(m, 2 H), 1.33 (m, 4 H), 0.89 (m, 3 H); 13C NMR (CDCl3) δ 121.7
(q, J ) 254 Hz), 71.6, 68.0, 66.5 (q, J ) 3.2 Hz), 29.2, 28.1, 22.5,
13.9; 19F NMR (CDCl3) δ -61.4; LRMS m/z 201 (M+ + 1, 1), 71
(100). Anal. Calcd for C8H15O2F3: C, 48.00; H, 7.55. Found: C,
47.95; H, 7.71.
Gen er a l P r oced u r e for th e P r ep a r a tion of CF 3O(CH2)2-
OSO2CF 3 (3) As Descr ibed by th e Rea ction of Eth er 2a
w ith (CF 3SO2)2O a n d CF 3SO3H. A mixture of 14 mL of (CF3-
SO2)2O (82 mmol), 0.5 mL of CF3SO3H (5.6 mmol), and 5.0 g of
trifluoromethyl ether 2a (21 mmol) was stirred at 60 °C over 48
h in a two-necked 50 mL round-bottomed flask equipped with a
OSO2CF3 3 and gave 0.49 g (66% yield) of CF3O(CH2)2SPh as a
colorless oil: bp 204-206 °C (Siwoloboff); 1H NMR (CDCl3) δ
7.41 (m, 2 H), 7.31 (m, 3 H), 4.09 (t, J ) 7.2 Hz, 2 H), 3.19 (t,
J ) 7.2 Hz, 2 H); 13C NMR (CDCl3) δ 134.1, 130.5, 129.2, 127.1,
121.5 (q, J ) 255 Hz), 65.5 (q, J ) 3.0 Hz), 32.5; 19F NMR (CDCl3)
δ -61.1; LRMS m/z 222 (M+, 45), 123 (100), 109 (22), 69 (30).
Anal. Calcd for C9H9F3O2: C, 48.64; H, 4.08. Found: C, 48.28;
H, 4.01.
P r ep a r a tion of CF 3O(CH2)2NHP h (6c). Similarly 6c was
prepared by the general procedure from 0.4 g (4.3 mmol) of
aniline, 0.32 g (3.2 mmol) of triethylamine, and 0.86 g (3.3 mmol)
of CF3O(CH2)2OSO2CF3 3 and gave after column chromatogra-
phy (SiO2, 20% CH2Cl2/pentane) 0.54 g (80% yield) of CF3O(CH2)2-
1
magnetic stirbar and
a reflux condenser under an argon
NHPh as a colorless oil: bp 184-186 °C (Siwoloboff); H NMR
atmosphere. Volatile compounds were removed under reduced
pressure (40 mmHg), and the residue was diluted with 50 mL
of CH2Cl2, washed with water, and dried (MgSO4). After removal
of the solvent under reduced pressure (40 mmHg), short-path
distillation (0.1 mmHg) of the residue gave 5.41 g (50% yield)
of CF3O(CH2)2OSO2CF3 as a colorless oil: bp 140-142 °C
(Siwoloboff); 1H NMR (CDCl3) δ 4.69 (m, 2 H), 4.27 (m, 2 H);
13C NMR (CDCl3) δ 121.3 (q, J ) 256 Hz), 118.5 (q, J ) 319
Hz), 72.6, 64.0 (q, J ) 3.6 Hz); 19F NMR (CDCl3) δ -75.1 (s,
3F), -62.1 (s, 3F); CIMS (CH4) m/z 263 (M+ + 1, 2), 243 (37),
177 (100). No satisfactory combustion analysis could be obtained
for this compound. Anal. Calcd for C4H4F6O4S: C, 18.33; H, 1.54.
Found: C, 16.96, H, 1.27. The derivatives, however (vide infra),
are well characterized.
(CDCl3) δ 7.30 (t, J ) 7.9 Hz, 2 H), 6.87 (t, J ) 7.4 Hz, 1 H),
6.71 (t, J ) 7.9 Hz, 2 H), 4.19 (t, J ) 5.4 Hz, 2 H), 3.96 (br s,
1H), 3.49 (t, J ) 5.4 Hz, 2 H); 13C NMR (CDCl3) δ 147.1, 129.3,
121.6 (q, J ) 254 Hz), 118.2, 113.1, 65.8 (q, J ) 3.0 Hz), 42.4;
19F NMR (CDCl3) δ -61.2; FTIR (CCl4) 3422, 3465 cm-1; LRMS
m/z 205 (M+, 24), 106 (100. Anal. Calcd for C9H10F3ON: C, 51.69;
H, 4.91; N, 6.83. Found: C, 51.66; H, 4.88; N, 6.71.
P r ep a r a tion of CF 3O(CH2)2C(Me)(CO2Et)2 (6d ). Similarly,
6d was prepared by minor variations of the general procedure
from 0.34 g (1.1 mmol) of 80% NaH in oil, 0.2 g (1.1 mmol) of
MeCH(CO2Et)2, and 0.3 g (1.1 mmol) of CF3O(CH2)2OSO2CF3
3 under an argon atmosphere and gave after neutralization with
NH4Cl extraction with CH2Cl2 and column chromatography
(Al2O3, 10% CH2Cl2/pentane), 0.25 g (77% yield) of CF3-
The byproduct (CF3SO2OCH2)2 (4) was isolated by column
chromatography (SiO2, CH2Cl2) from the residue left after the
short path distillation, and had the following properties: 1H
NMR (CDCl3) δ 4.78 (s); 13C NMR (CDCl3) δ 118.5 (q, J ) 319
Hz), 71.7; 19F NMR (CDCl3) δ -74.8 (s); CIMS (NH3) m/z 344
(M + NH4+, 100), 177 (98).
P r ep a r a tion of CF 3O(CH2)2OSO2CF 3 (3) fr om Eth er 2b.
Similarly, 3 was prepared by the general procedure from 3.5 mL
of (CF3SO2)2O (20 mmol), 0.1 mL of CF3SO3H (1.13 mmol), and
1.0 g of trifluoromethyl ether 2a (5 mmol). Short-path distillation
was not performed. Instead, column chromatography of the crude
residue (SiO2, 10% Et2O/ pentane) gave 0.36 g (28% yield) of
CF3O(CH2)2OSO2CF3 3, 0.43 g (27% yield) of (CFSO2OCH2)2 4,
and 0.29 g (19% yield) of a new byproduct CF3O(CH2)2O(CH2)2-
OSO2CF3 (5) with the following characteristics: bp 156-158 °C
(Siwoloboff, dec); 1H NMR (CDCl3) δ 4.63 (m, 2 H), 4.11 (m, 2
H), 3.83 (m, 2 H), 3.76 (m, 2 H); 13C NMR (CDCl3) δ 121.6 (q,
J ) 255 Hz), 118.6 (q, J ) 319 Hz), 75.3, 68.8, 68.5, 66.4 (q, J )
3.2 Hz); 19F NMR (CDCl3) δ -75.2 (s, 3F), -61.6 (s, 3F); CIMS
(NH3) m/z 324 (M + NH4+, 100). Anal. Calcd for C8H15O2F3: C,
23.54; H, 2.63. Found: C, 23.56; H, 2.65.
O(CH2)2C(Me)(CO2Et)2 as
a colorless oil: bp 210-212 °C
1
(Siwoloboff); H NMR (CDCl3) δ 4.16 (q, J ) 7.1 Hz, 4 H), 4.06
(t, J ) 6.6 Hz, 2 H), 2.26 (t, J ) 6.6 Hz, 2 H), 1.44 (s, 3H), 1.22
(t, J ) 7.1 Hz, 6 H); 13C NMR (CDCl3) δ 171.4, 121.4 (q, J ) 255
Hz), 63.7 (q, J ) 3.5 Hz), 61.5, 51.6, 34.4, 20.1, 13.8; 19F NMR
(CDCl3) δ -61.6; FTIR (CCl4) 1732, 1764 cm-1; LRMS m/z 286
(M+, 4), 241 (81), 214 (32), 174 (95), 128 (69), 115 (81), 100 (99),
69 (100). Anal. Calcd for C11H17F3O5: C, 46.16; H, 5.99. Found:
C,46.47; H, 6.06.
P r ep a r a tion of N-[2-(Tr iflu or om eth oxy)eth yl]p h th a l-
im id e (6e). Similarly, 6e was prepared by minor variations of
the general procedure from 1 g (5.4 mmol) of potassium phthal-
imide and 0.86 g (3.3 mmol) of CF3O(CH2)2OSO2CF3 3 and gave
after extraction with CH2Cl2 and column chromatography (SiO2,
CH2Cl2 gradient/pentane), 0.71 g (84% yield) of N-[2-(trifluo-
romethoxy)ethyl]phthalimide as white crystals: mp 77.0-77.4
°C; 1H NMR (CDCl3) δ 7.82 (m, 2 H), 7.71 (m, 2 H), 4.19 (t, J )
5.6 Hz, 2 H), 3.98 (t, J ) 5.6 Hz, 2 H); 13C NMR (CDCl3) δ 167.7,
134.1, 131.7, 123.4, 121.4 (q, J ) 255 Hz), 63.8 (q, J ) 3.2 Hz),
36.6; 19F NMR (CDCl3) δ -61.4; FTIR (CCl4) 1727 cm-1; LRMS
m/z 259 (M+, 24), 190 (100). Anal. Calcd for C11H8F3O3N: C,
50.98; H, 3.11; N, 5.40. Found: C, 50.85; H, 3.11; N, 5.18.
P r ep a r a tion of CF 3O(CH2)2NH2 (6f). A solution of 0.7 g (2.7
mmol) of phthalimide 6e and 0.16 g (3.2 mmol) of hydrazine
hydrate in 25 mL of MeOH was refluxed during 2 h. The mixture
was cooled to 0 °C, 3 mL of 3 M HCl was added, and the mixture
was refluxed again for 1 h. After the mixture was cooled to room
temperature, the solid was filtered and washed with water (2 ×
5 mL). The resulting aqueous phase was extracted with Et2O
(3 × 15 mL), and the ethereal layer was dried with MgSO4. After
filtration, the organic phase was saturated with gaseous HCl,
followed by evaporation of the solvent and gave 0.31 g (70% yield)
of the hydrochloride salt of CF3O(CH2)2NH2 as an hygroscopic
white powder: mp 189.4-191.0 °C dec; 1H NMR (D2O) δ 4.18
(br t, 2 H), 3.21 (br t, 2 H); 13C NMR (D2O) δ 123.8 (q, J ) 255
Hz), 66.4 (q, J ) 3.4 Hz), 41.0; 19F NMR (D2O) δ -59.9; FTIR
(Nujol mull) 3037 cm-1; POS ESIMS m/z 130 (M+, 100). Anal.
Calcd for C3H7ClF3NO: C, 21.93; H, 4.17; N, 8.08. Found: C,
21.77; H, 4.26; N, 8.46.
P r ep a r a tion of CF 3O(CH2)2OSO2CF 3 (3) fr om Eth er 2c.
Similarly 3 was prepared by the general procedure from 3.5 mL
of (CF3SO2)2O (20 mmol), 0.1 mL of CF3SO3H (1.13 mmol), and
1.0 g of trifluoromethyl ether 2c (5 mmol) and gave after
Kugelrohr distillation (75 °C, 15 mmHg) 0.96 g (73% yield) of
CF3O(CH2)2OSO2CF3.
Gen er a l P r oced u r e for th e Alk yla tion of Nu cleop h iles
w ith CF 3O(CH2)2OSO2CF 3 (3) As Descr ibed by th e P r ep a -
r a tion of CF 3O(CH2)2OP h (6a ). Sodium phenoxide (0.42 g, 3.6
mmol) was added to a stirred solution of 0.86 g (3.3 mmol) of
CF3O(CH2)2OSO2CF3 3 in 25 mL of THF. The mixture was
stirred for 48 h. After addition of water (20 mL) and basification
with saturated NaHCO3 solution, the mixture was extracted
with Et2O (3 × 20 mL). Drying of the organic layer (MgSO4)
followed by concentration under vacuum and flash chromatog-
raphy of the residue (SiO2, CH2Cl2) gave 0.67 g (90% yield) of
CF3O(CH2)2OPh as a colorless oil: bp 182-184 °C (Siwoloboff);
1H NMR (CDCl3) δ 7.43 (t, J ) 8.0 Hz, 2 H), 7.13 (t, J ) 7.4 Hz,
1 H), 7.04 (d, J ) 8.0 Hz, 2 H), 4.36 (m, 2 H), 4.23 (m, 2 H); 13
C
NMR (CDCl3) δ 158.2, 129.5, 121.7 (q, J ) 254 Hz), 121.4, 114.6,
65.6 (q, J ) 3.3 Hz), 65.2; 19F NMR (CDCl3) δ -61.4; LRMS m/z
206 (M+, 64), 106 (30), 94 (100), 77 (42), 69 (31). Anal. Calcd for
C9H9F3O2: C, 52.43; H, 4.40. Found: C, 52.41; H, 4.51.
P r ep a r a tion of CF 3O(CH2)2SP h (6b). Similarly, 6b was
prepared by the general procedure from 0.57 g (3.8 mmol)
potassium thiophenoxide and 0.86 g (3.3 mmol) of CF3O(CH2)2-
Ack n ow led gm en t. This work is part of the Euro-
pean TMR program ERB FMRX-CT970120, entitled
“Fluorine As a Unique Tool for Engineering Molecular
Properties”.
J O005701T