Synthesis of polyfluorinated tertiary alcohols using ring opening reactions of 2,2-bis(trifluoromethyl)oxirane

Article abstract of DOI:10.1055/s-2002-34857

This paper describes new reactions of 2,2-bis(trifluoromethyl)oxirane (1). Ring opening of 1 by oxygen, nitrogen, sulfur or carbon nucleophiles (Nu^-) proceeds regioselectively, with exclusive formation of tertiary alcohols: NuCH₂C(CF₃)₂OH. The reaction of 1 with strong acids (HX) is also regioselective and proceeds under mild conditions leading to the formation of XCH₂C(CF₃)₂OH (X = FSO₂O, CF₃SO₂O, Cl, I). The addition of acetic acid to 1, however, requires an elevated temperature and TaF₅ a catalyst. Highly selective reactions of 1 with nucleophilic or electrophilic reagents provide a simple and general route to materials containing CH₂C(CF₃)₂OH group.

Full text of DOI:10.1055/s-2002-34857

PAPER
2225
Synthesis of Polyfluorinated Tertiary Alcohols Using Ring Opening Reactions
of 2,2-Bis(trifluoromethyl)oxirane1
R
ing Opening Rea
i
c
tions
o
a
f
2,2-Bis(t
c
rifluoromet
hhyl)oxirane eslav A. Petrov*
DuPont Central Research and Development, Experimental Station, P.O. Box 80328, Wilmington, Delaware 19880-0328, USA
E-mail: Viacheslav.A.Petrov@USA.Dupont.com
Received 24 May 2002; revised 28 July 2002
rane is still limited to very few transformations, i.e.
Abstract: This paper describes new reactions of 2,2-bis(trifluoro-
interaction with ammonia and methylamine.8 Recently
methyl)oxirane (1). Ring opening of 1 by oxygen, nitrogen, sulfur
developed simple and practical synthesis of 19 made this
or carbon nucleophiles (Nu–) proceeds regioselectively, with exclu-
sive formation of tertiary alcohols: NuCH2C(CF3)2OH. The reac-
material readily available on a multigram scale. The de-
tion of 1 with strong acids (HX) is also regioselective and proceeds tailed investigation of reactivity of 1 is presented in this
under mild conditions leading to the formation of XCH2C(CF3)2OH
paper.
(X = FSO2O, CF3SO2O, Cl, I). The addition of acetic acid to 1, how-
ever, requires an elevated temperature and TaF5 a catalyst. Highly
selective reactions of 1 with nucleophilic or electrophilic reagents
Reactions with Nucleophiles
provide a simple and general route to materials containing
CH2C(CF3)2OH group.
The strong electron-withdrawing effect of two CF3-
groups in 2,2-bis(trifluoromethyl)oxirane (1) leads to the
Key words, 2,2-bis(trifluoromethyl)oxirane, ring opening reac-
tions, nucleophilic addition, electrophilic addition, epoxides
development of a substantial positive charge on the car-
bon bearing two hydrogen substituents and makes 1 sus-
ceptible to nucleophilic attacks. Even a relatively weak
nucleophile, such as water, reacts with 1 in the absence of
a catalyst, although only at elevated temperature
(Scheme 1). The diol 210 was isolated in this reaction as a
1:1 mixture with THF solvent.
Introduction
Development of a new generation of photoresist polymers
for 157 nm microlithography requires preparation of poly-
mers, which must be base-soluble, but at the same time
highly transparent in the vacuum UV region of the spec-
trum. It has been demonstrated2 that this goal can be
achieved by the introduction of a C(CF3)2OH fragment
into the polymer backbone, since this group has low ab-
sorbance at 157 nm, and is acidic enough to provide the
solubility of the polymer in conventional aqueous-base
developers.
175 °C, 12 h
F3C
HOCH2C(CF3)2OH
+ H2O
F3C
O
THF
2, 55%,
at 60% conversion
1
Scheme 1
Separation of 2 and solvent proved to be difficult due to
the combination of high solubility of 2 in water and for-
mation of a complex between relatively acidic diol and
THF. More convenient synthesis of 2 is based on hydrol-
ysis of acetate 2a under basic conditions (Scheme 2) (for
preparation of 2a see next section).
Methods to introduce the C(CF3)2OH group into organic
molecules are limited to reactions of hexafluoroacetone
with organic substrates3 or the reaction of the synthetic
equivalents of trifluoromethyl anion,4a,b especially
CF3SiMe34c with carbonyl compounds. In search of a new
methodology for introduction of the C(CF3)2OH fragment
into organic substrates we chose 2,2-bis(trifluorometh-
yl)oxirane (1), since ring opening reactions of 1 can po-
tentially lead to materials containing the CH2C(CF3)2OH
group. Similar reactions of its closest analogue, trifluor-
omethyloxirane, are indeed regiospecific, resulting in the
formation of secondary -trifluormethyl alcohols.5
CH3C(O)OCH2C(CF3)2OH + KOH/CH3OH
2a
1) 25 °C, 1h
2) H+
2, 68%
Scheme 2
Despite the fact that compound 1 was prepared for over
30 years ago (along with a few others epoxides of this
type by the reaction of diazomethane with polyfluoroace-
tones 6–8), the chemistry of 2,2-bis(trifluoromethyl)oxi-
The diol 2 was isolated after acidification of the reaction
mixture by 10% hydrochloric acid and extraction with
CH2Cl2 or Et2O (see Experimental Part). The diol 2 con-
taminated with water could be a liquid,10 however pure,
water-free material was found to be a solid (mp 45–
47 °C). At ambient temperature, epoxide 1 did not react
with alcohols. However, the addition of 1 to a solution of
alkoxides 3a,b in THF resulted in fast, exothermic ring
Synthesis 2002, No. 15, Print: 29 10 2002.
Art Id.1437-210X,E;2002,0,15,2225,2231,ftx,en;M02002SS.pdf.
© Georg Thieme Verlag Stuttgart · New York
ISSN 0039-7881

2226
V. A. Petrov
PAPER
The reverse orientation of ring opening reactions of 1
(compared to octafluoroisobutene oxide) is a strong indi-
cation that in this case, the direction of the nucleophilic
ring opening is governed by electronic, but not steric fac-
tors, as it was earlier suggested for reactions of trifluorom-
ethyloxirane.5a
The reaction of 1 with excess of ammonia or ammonium
hydroxide at low or ambient temperature gave primary
amine 68 as a major product, along with a smaller amount
of secondary amine 6a (Scheme 5).
Scheme 3
opening reaction with the formation of compounds 4a,b.
The anion 4c formed as an intermediate was intercepted
and converted into the ether 4d (Scheme 3).
The synthesis of hydroxyether 5 (isomer of 4a) was con-
ducted by methylation of the C(CF3)2OH group of the es-
ter 2a with dimethyl sulfate, followed by deprotection of
the primary alcohol function by basic hydrolysis
(Scheme 4).
Scheme 5
2a + (CH3)2SO4
K2CO3
At higher temperature, in the reaction of 1 and NH4OH,
the amine 6a was produced as the sole product in high
yield (Scheme 6).
CH3C(O)OCH2C(CF3)2OCH3
1)C2H5OH/KOH
2) H+
60 °C, 1 h
1 + NH4OH
HN[CH2C(CF3)2OH]2
6a
HOCH2C(CF3)2OCH3
yield 82%
5, 70%
Scheme 6
Scheme 4
Surprisingly, the alkylation of 6a by another equivalent of
epoxide 1 was found to be difficult. Only a trace of the
corresponding tertiary amine was detected in the reaction
of 6a and 1 at elevated temperature in a closed system
(170 °C, diethyl ether) by GC/MS. This result can be ex-
plained in terms of steric hindrance created by two bulky
CH2C(CF3)2OH substituents in the molecule of 6a, since
the reaction of trifluoromethyloxirane and NH4OH was
reported to give N[CH2CH(OH)CF3]3 at ambient temper-
ature.14
Compound 2a used in this experiment was prepared by
the reported method involving radical addition of methyl
acetate to hexafluoroacetone.11
Despite structural similarity of 4a and 5, there is a notice-
able difference in chemical shifts of C(CF3)2OH and
C(CF3)2OCH3 groups in 19F NMR spectra. Introduction of
a substituent to oxygen results in the substantial downfield
shift of the resonance of (CF3)2C ( = –77.6 for 4a and
–71.5 ppm for 5; in CDCl3). Independent synthesis of 5
combined with NMR data of compounds 4a and 5 allow
unambiguous assignment of structure 4a to the material
formed in the reaction of 1 with sodium methoxide. The
absence of a detectable amount of isomeric 5 in the crude
reaction mixture (GC, NMR) is an indication of high
regioselectivity of the ring-opening reaction of 1. Attack
of the nucleophile occurs on the CH2 group of 1 leading to
selective formation of the corresponding tertiary alcohol.
It should be also pointed out that nucleophilic attack on
perfluorinated oxiranes, such as oxides of hexafluoro-
propene12a,bor octafluoroisobutene,12a,c takes place at the
sterically hindered carbon bearing trifluoromethyl
group(s), with only a few exceptions reported for hexa-
fluoropropene epoxide.12a,13 For example, octafluoro-
isobutene epoxide reacts with Nu– forming derivatives of
hexafluoroisobutyric acid.12c In light of these data, the re-
activity of 1 actually resembles the reactivity of trifluoro-
methyloxirane,5 rather than octafluoroisobutene epoxide.
The epoxide 1 rapidly reacts with diethylamine (7a) and
anilines 7b,c under mild conditions in the absence of sol-
vent to give the corresponding adducts 8a–c in moderate
to high yield (Scheme 7).
Scheme 7
The addition of thiol 9 to 1 proceeds at ambient tempera-
ture in dry DMF solvent without a catalyst leading to 10
(Scheme 8).
Synthesis 2002, No. 15, 2225–2231 ISSN 0039-7881 © Thieme Stuttgart · New York

PAPER
Ring Opening Reactions of 2,2-Bis(trifluoromethyl)oxirane
2227
25 °C, 6 h
DMF
C6F13CH2CH2SCH2C(CF3)2OH
1 + C6F13CH2CH2SH
9
10, 43%
Scheme 8
Scheme 11
The reaction of 1 with methylmagnesium iodide was only
briefly mentioned in Ref.8 As it was found in this study,
the reaction between 1 and i-PrMgCl or PhMgBr is sur-
prisingly slow in diethyl ether or THF as solvent. In both
cases the conversion of 1 did not exceed 20% even after
one week at ambient temperature. However, several years
ago it was demonstrated that CuI could significantly ac-
celerate the reaction of trifluoromethyloxirane with Grig-
nard reagents.15 The addition of a catalytic amount of CuI
also had a drastic effect on the reaction of 1 with arylmag-
nesium bromides. The reaction in the presence of CuI cat-
alyst rapidly proceeds at low temperature leading to the
formation of aryl derivatives 12,16 13a and 13b
(Scheme 9).
BF3 OEt2, SbF5 or glacial acetic acid at ambient temper-
ature. On the other hand, the reaction of 1 with much
stronger protic acids, trifluoromethanesulfonic or fluoro-
sulfonic acid, proceeds rapidly at ambient or slightly ele-
vated temperature, selectively leading to the
corresponding -hydroxysulfonates 15a,b (Scheme 11).
It seems that epoxide 1 is more active in reaction with pro-
tic acids compared to perfluorinated epoxides. For exam-
ple, hexafluoropropene oxide was reported to react with
HOSO2F only at elevated temperature (>150 °C).19 Acetic
acid can be added to 1, although this reaction proceeds
only in the presence of Lewis acid catalyst at elevated
temperature (Scheme 12).
130 °C, 12h
1 + CH3C(O)OH
CH3C(O)OCH2C(CF3)2OH
TaF5
2a, 68%
Scheme 12
Scheme 9
This transformation provides an easy access to acetate 2a,
which was previously prepared by prolonged UV irradia-
tion of a mixture of hexafluoroacetone and methyl ace-
tate.11 Similar to the reported reaction of 2,2-
(chlorodifluoromethyl)oxirane with hydrobromic acid,7 1
rapidly reacts with concentrated hydrochloric or hy-
droiodic acids at 25–40 °C producing halohydrines 16a20
and 16b (Scheme 13).
Moderate yields of 12, 13a,b in this reaction are the result
of a side reaction, the formation of BrCH2C(CF3)2OH17
(confirmed by NMR of the crude reaction mixture). It
should be also pointed out that the formation of the corre-
sponding bromohydrin was previously reported in the re-
action of trifluoromethyloxirane with MgBr2 and
CH3MgBr.18 The epoxide 1 seems to be more susceptible
to attack by Br– since the formation of the corresponding
bromohydrin in the reactions of trifluoromethyloxirane
with Grignard reagents catalyzed by CuI was not report-
ed.15
20-35 °C, 2-3h
XCH2C(CF3)2OH
1 + HX
H2O
X=Cl, 16a, 88%
X=I, 16b, 71%
The reaction of 1 with hexafluoroacetone in the presence
of dry CsF results in the formation of dioxolane 14
(Scheme 10).
Scheme 13
Analogous to trifluoromethyloxirane,15 the epoxide 1 can
be used as an alkylating agent for aromatic compounds.
For example, the reaction between benzene, and 1 cata-
lyzed by AlCl3, resulted in the formation of 12, along with
chlorohydrin 16a as a byproduct (Scheme 14). The forma-
tion of 16a, probably is the result of addition of HCl to the
epoxide catalyzed by AlCl3.
CF3
CsF
CH3CN
CF3
1 + (CF3)2C=O
O
O
F3C
CF3
14, 24%
Scheme 10
10-25 °C, 3h
1 + C6H6
12 + 16a
AlCl3
ratio 12 : 16a - 3:1
yield of 12 - 63%
Reactions with Electrophiles
Electron-withdrawing effect of two trifluoromethyl
groups attached to the carbon of the oxirane ring signifi-
cantly decreases the basicity of the oxygen atom of ep-
oxide 1, resulting in reduced reactivity towards
electrophiles. For example, compound 1 did not react with
Scheme 14
Compounds containing CH2C(CF3)2OH group could be
converted into the corresponding olefins by elimination of
water, using a method previously developed for the dehy-
Synthesis 2002, No. 15, 2225–2231 ISSN 0039-7881 © Thieme Stuttgart · New York

2228
V. A. Petrov
PAPER
dration of CH3C(CF3)2OH.21 Heating the compounds 13a,
or 13b with excess PCl5 resulted in the formation of ole-
fins 17a22 or 17b in good yields (Scheme 15).
Conclusion
The epoxide 1 has relatively high reactivity towards both
nucleophilic and electrophilic reagents. Both types of
ring-opening reactions of 1 are regioselective and proceed
with formation of tertiary alcohols providing a simple
method of the introduction the CH2C(CF3)2OH group into
organic compounds and giving an access to a variety of
new polyfluorinated tertiary alcohols.
Scheme 15
The conditions and yields for the reactions of 1 and the
spectral data of compounds prepared are given in Tables 1
and 2.
Table 1 Conditions and Yields for the Reactions of 2,2-Bis(trifluoromethyl)oxirane (1)
Entry
1
Reagents (mol)
Solvent (mL)
THF (100)
Time (h)
12
Temp. (°C) Product
Yield (%)
55a
bp (°C)/mm Hg
–
1 (0.1),
175
2
H2O (0.11)
2
3
1 (0.1), MeONa (0.1)
THF (100)
1
10–25
4a
5
60
62–63/110
2a (0.1),
K2CO3 (0.11), Me2SO4 (0.1)
MeCN
(100)
14
25
70b
125–126/760
4
5
6
7
1 (0.1),
7a (0.1)
Et2O
(100)
3
25–33
25
8a
8c
83
75
43
40
71/5
1 (0.055),
7c (0.055)
CH2Cl2
(10)
16
117–118/12
(mp 35–36)
1 (0.025),
9 (0.025)
DMF (50)
25
16
10
25–26/0.1
1 (0.1),
THF (100)
0–25
14
12
101–103/53c
11a (0.1),
CuI (1 mol%)
8
9
1 (0.11),
11c (0.1),
CuI (1 mol%)
THF (100)
–
10–25
0–25
16
3
13b
15b
32
78
92–93/10
–
1 (0.2),
CF3SO2OH
(0.25)
10
11
12
1 (0.56),
–
–
–
25–85
25–60
10
16
6
16a
16b
12
88
71
63f
84–85/760
41–42/55
–
HCl (100 mL)d
1 (0.56),
HI (100 mL)e
1 (0.055),
1
C6H6 (0.26),
AlCl3 (0.004)
13
13a (0.031),
–
16
110–130
17a
69g
73–74/10
PCl5 (0.04)
a Reaction was carried out in a 240 mL Hastelloy shaker tube, compound 2 was isolated as 1:1 mixture with THF; calculated yield (NMR).
b One-pot reaction; after dilution of the reaction mixture with H2O (200 mL), the separated lower layer was treated with a 10% solution of KOH
in MeOH (100 mL) for 30 min, diluted with H2O (200 mL), the organic layer was separated, dried (MgSO4) and distilled.
c According Ref.16 isolated material was a colorless viscous oil.
d Concd HCl (36 wt%).
e Concd HI (48 wt%).
f The crude product also contained 16a (ratio 12:16a = 3:1, NMR).
g At 90% conversion (NMR).
Synthesis 2002, No. 15, 2225–2231 ISSN 0039-7881 © Thieme Stuttgart · New York

PAPER
Ring Opening Reactions of 2,2-Bis(trifluoromethyl)oxirane
2229
Table 2 NMR and IR Data for New Compounds
Entry Product 1H NMRa
19F NMRa
, J (Hz)
IR
, J (Hz)
(cm–1)
1
2
3
4
1b
3.3 (s)
–73.3 (s)
–77.3 (s)
–77.5 (s)
1404, 1368c
3490
2d
2.3(1 H, br s), 4.0 (2 H, s), 4.2 (1 H, br s)
3.5 (3 H, s), 3.8 (hept, J = 0.8), 4.3 (br s)
4ae
4b
3485
1.3 (6 H, d, J = 6.0), 3.8 (1 H, m), 3.8 (2 H, m), –77.6 (s)
3426
4.2 (1 H, br s)
5
6
4d
5f
3.45 (3 H, s), 3.47(3 H, hept, J = 1.0), 3.9 (2 H, –71.5 (s)
hept, J = 3.0)
–
2.5 (1 H, br s), 3.7 (3 H, hept, J = 1.1), 4.1 (2 H, –73.9 (s)
3485
s)
7
8
9
6
2.8 (3 H, br s), 3.3 (2 H, s)
3.1 (3 H, br s), 3.2 (4 H, s)
–78.5
3395, 3333
3400, 3380g
6a
8a
–77.5 (s)
1.0 (6 H, t, J = 7.6), 2.7 (4 H, q, J = 7.6), 2.8 (2 –78.6 (s)
3083, 2978, 2872
H, s), 6.7 (1 H, br s)
10
8b
8c
3.8 (2 H, s), 4.3 (1 H, br s), 4.2 (1 H, br s), 6.8 –78.0 (s)
(2 H, d, J = 8.0), 7.0 (1 H, t, J = 8.0), 7.3 (2
H, t, J = 8.0)
–
11
12
3.6 (2 H, s), 4.1 (1 H, br s), 6.9 (2 H, m, J = 9.0), –77.9 (3 F, s), –123.1 (1 F, m)
7.9 (2 H, t, J = 9.0)
3424, 3378g
10
2.5 (2 H, m), 2.9 (2 H, m), 3.2 (2 H, s), 4.2 (1
H, br s)
–77.9 (6 F, s), –81.4 (3 F, t, J = 7.5), –114.6 (2 F, m), 3389
–122.4 (2 F, m),
–123.3 (2 F, m), –123.8 (2 F, m),
–126.6 (2 F, m)
13
14
15
13a
13b
14h
2.8 (1 H, br s), 3.1 (2 H, s), 7.3 (2 H, m), 7.4 (2 –63.2 (3 F, s), –76.5 (6 F, s)
H, m)
3589
3590
–
3.0 (1 H, br s), 3.3 (2 H, s), 7.5 (2 H, d, J = 8.0), –62.1 (3 F, s), –76.4 (6 F, s)
7.6 (2 H, d, J = 8.0)
4.7 (s)
–74.3 (6 F, hept, J = 0.5),
–77.6 (6 F, hept, J = 0.5)
16
17
18
19
20
15a
15b
16a
16b
17a
4.1 (1 H, br s), 4.8 (2 H, s)
3.3 (1 H, br s), 4.5 (2 H, s)
3.6 (1 H, br s), 3.9 (2 H, s)
3.2 (1 H, br s), 3.5 (2 H, s)
7.6 (2 H, m), 7.7 (3 H, m)
36.9 (1 F, s), –77.1 (6 F, s)
–74.7 (3 F, s), –76.2 (6 F, s)
–76.1 (s)
–
3507, 1426
3530
–75.8 (s)
3507
–57.9 (3 F, q, J = 7.2), –63.4 (3 F, s), –64.3 (3 F, qd, 1669
J = 7.2, 1.2)
21
17b
7.2 (1 H, s), 7.5 (2 H, m), 7.9 (2 H, m)
–57.9 (3 F, q, J = 7.0), –63.5 (3 F, s), –64.4 (3 F, qd, 1670
J = 7.0, 1.2)
a In CDCl3.
b 13C{H} NMR (CDCl3): = 46.8 (s), 55.0 (hept, J = 37 Hz), 120.8 (q, J = 275 Hz).
c Gas phase.
d Lit.:10 19F NMR (standard CF3CO2H, in DMSO-d6): = 11.68.
e 13C{H} NMR (neat): = 59.2 (s), 68.1 (s), 75.3 (hept, J = 28 Hz), 122.9 (q, J = 289 Hz).
f In acetone-d6; 13C{H} NMR (neat): = 54.3 (s), 59.0 (s), 80.4 (hept, J = 26 Hz), 123.0 (q, J = 285 Hz).
g In KBr.
h 13C{H} NMR (neat): = 70.1 (s), 84.6 (hept, J = 29 Hz), 105.2 (hept, J = 33 Hz), 119.8 (q, J = 291 Hz), 121.1 (q, J = 285 Hz).
Synthesis 2002, No. 15, 2225–2231 ISSN 0039-7881 © Thieme Stuttgart · New York

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V. A. Petrov
PAPER
19F and 1H NMR spectra were recorded on QE-300 (General Elec-
tric, 200 MHz) or Bruker DRX-400 instruments (376.8485 and
400.5524 MHz respectively) using CFCl3 and TMS as an internal
standard and CDCl3 or acetone-d6 as a lock solvents. IR spectra
were recorded on a Perkin-Elmer 1600 FT spectrometer as films or
KBr pellets. GC and GC/MS analysis were carried out on a HP 6890
instrument using HP FFAP capillary column (30 m) and TC (GC)
or mass-selective (GC/MS) detectors.
Tables 1 and 2.
1,1,1,3,3,3-Hexafluoro-2-methoxy-2-(methoxymethyl)propane
(4d)
NaH (98%, 5 g, 0.21mol) was placed in a 500-mL flask inside a dry
box. Anhyd THF (100 mL) was introduced into the flask under a N2
blanket using a syringe. A solution of MeOH (7.1g, 0.22 mol) in an-
hyd THF (100 mL) was slowly added using an addition funnel to
keep the temperature between 30–35 °C. The reaction mixture was
stirred for 30 min, cooled down to 15 °C and compound 1 (36 g, 0.2
mol) was added dropwise to keep the temperature of the mixture at
15–20 °C. After 14 h, Me2SO4 (10 mL, 12.0 g, 0.095 mol) was add-
ed dropwise at 25–30 °C. After 1 h, the mixture was diluted with
H2O, the organic layer was separated, and dried (MgSO4). The
crude product (45 g, a mixture of 40% ether 4d and 60% of alcohol
4a, GC, NMR) was distilled to give 22 g of a fraction with bp 100–
120 °C (mixture of 4d and 4a, 70:30). Pure 4d was isolated by
washing this fraction with 10% NaOH. Redistillation of the dried
product afforded 15 g (33%) of 4d; bp 120.3–120.5 °C (Table 2).
Anhyd solvents, alcohols, NaH (98%), Et2NH, anilines, BF3-ether-
ate, benzene, anhyd AlCl3 (Aldrich); FSO2OH, hexafluoroacetone,
CF3SO2OH, SbF5 (Synquest); C6F13(CH2)2SH (Ciba-Geigy),
(CF3)2C=CH2 (DuPont) are commercially available and used with-
out further purification. Reagents 11a–c were prepared by the addi-
tion of the corresponding aryl bromides to Mg turnings (30%
excess) in THF solvent at 30–40 °C. These solutions were filtered
under N2 and used immediately. The epoxide 1 was prepared ac-
cording to reported procedure.9 Due to its relatively low boiling
point (39 °C,8 41–42 °C9) and high vapor pressure, most of the re-
actions were carried out in a reactor equipped with a dry-ice con-
denser to prevent loss of the epoxide.
Anal. Calcd for C5H6F6O2: C, 31.57, H, 3.57. Found: C, 31.97, H,
3.51.
Compounds 2,10 2a,11 6,812,16 16a,20 and 17a22 were identified by
comparison of boiling points or NMR data with reported values.
2-(Aminomethyl)-1,1,1,3,3,3-hexafluoropropane-2-ol (6)
Compound 1 (54 g, 0.3 mol) 1 was slowly added to a stirred mixture
of 30% NH4OH (100 mL) and Et2O (100 mL) at 25–30 °C ( 1 h).
The reaction mixture was stirred for 2 h at 25 °C, the organic layer
was separated, and the aqueous layer was extracted with Et2O
(2 50 mL). The organic layers were combined, dried (MgSO4), the
solvent was removed under vacuum (15–20 °C) and the crude solid
product (mixture of 6 and 6a, ratio 5:1, NMR) was distilled to give
37.8 g (64%) of 6; bp 134–137 °C/760 mm Hg, which crystallized
on standing; mp 75–76 °C (Lit.7mp 76–77 °C) (Table 2).
Caution! Hexafluoroactone is a highly toxic material and should be
handled in a well-ventilated hood to avoid contact with its vapor.
The epoxide 1 and compounds prepared in this work are materials
whose toxicological properties are not fully explored, and these ma-
terials should be handled accordingly.
Reactions with Nucleophiles; 3,3,3-Trifluoro-2-(trifluorometh-
yl)propane-1,2-diol (2) by Hydrolysis of 2a
Compound 2a (48 g, 0.2 mol) was added dropwise to a stirred solu-
tion of KOH (30 g, 0.54 mol) in anhyd MeOH (150 mL) at 45–
50 °C. The reaction mixture was kept at 50 °C for 30 min, cooled
down to 10 °C and aq 20% HCl (200 mL) was slowly added. The
mixture (pH 1) was extracted with Et2O (3 100 mL), the com-
bined organic layers were dried (MgSO4), the solvent was distilled
off at atmospheric pressure, and the residue was distilled to give 27
g (68%) of 2; bp 136–137 °C which crystallized on standing; mp
45–47 °C (Tables 1 and 2).
Anal. Calcd for C4H5F6NO: C, 24.38, H, 2.56, N, 7.11. Found: C,
24.63, H, 2.27, N, 7.11.
1,1,1,3,3,3-Hexafluoro-2-({[3,3,3-trifluoro-2-hydroxy-2-(tri-
fluoromethyl)propyl]amino}methyl)propan-2-ol (6a)
Compound 1 (80 g, 0.44 mol) was slowly added to a stirred 30%
NH4OH (20 mL) at 25–60 °C. The reaction mixture was kept at
60 °C for 1 h and cooled down to 25 °C. The crystallized crude
product was dissolved in Et2O (200 mL), the Et2O solution was
dried (MgSO4), the solvent was removed under vacuum, and the
crude product was recrystallized from hexane to give 68 g (82%) of
6a; mp 90–91 °C (Table 2).
Anal. Calcd for C4H4F6O2: C, 24.26, H, 2.04. Found: C, 24.26, H,
1.96.
1,1,1,3,3,3-Hexafluoro-2-(isopropoxymethyl)propane-2-ol (4b);
Typical Procedure
Anal. Calcd for C8H7F12NO2: C, 25.48, H, 1.87, N, 3.71. Found: C,
25.28, H, 1.64, N, 3.82.
NaH (98%, 5 g, 0.21 mol) was placed in a 500-mL flask inside a dry
box. Anhyd THF (100 mL) was introduced into the flask under a N2
blanket using a syringe. A solution of i-PrOH (12 g, 0.2 mol) in an-
hyd THF (100 mL) was slowly added using an addition funnel to
maintain the internal temperature at 30–35 °C. The reaction mixture
was stirred for 1 h at 35 °C, cooled down to 15 °C and compound 1
(36 g, 0.2 mol) was added dropwise to keep the temperature of the
reaction mixture below 20 °C. After 14 h, MeOH (10 mL) was add-
ed and the mixture was diluted with 10% HCl (500 mL). The organ-
ic layer was separated and the aqueous layer was extracted with
CH2Cl2 (2 100 mL). The combined organic layers were dried
(MgSO4), the solvent was removed under vacuum and the residue
was distilled to give 13 g of a fraction with bp 66–71 °C/100 mm
Hg (mixture of 4b and THF, 1:1) and 37 g of a fraction with bp 71–
73 °C/100 mm Hg (4b 95%, 5% of THF). The calculated yield of
4b was 90% (Table 2).
2-(Anilinomethyl)-1,1,1,3,3,3-hexafluoropropan-2-ol (8b); Typ-
ical Procedure
Compound 1 (15 g, 0.083 mol) was added dropwise to C6H5NH2 (10
mL, 10.2 g, 0.11 mol) with stirring over a period of 1 h at 15–20 °C.
After the addition was over, the reaction mixture was kept at 25 °C
for 16 h and distilled to give 15 g (66%) of 8b; bp 112–113 °C/10
mm Hg, which crystallized on standing; mp 34–35 °C (Table 2).
Anal. Calcd for C10H9F6NO: C, 43.97, H, 3.32, F, 40.53. Found: C,
43.46, H, 3.26, F, 40.73.
Compounds 8a,c, and 10
These compounds were prepared similarly (Tables 1 and 2).
1,1,1,3,3,3-Hexafluoro-2-[3-(trifluoromethyl)benzyl]propan-2-
ol (13a); Typical Procedure
+
MS: m/z = 240 [M+, C7H10F6O2 ].
To a solution of 11a prepared by reacting Mg turnings (2.8 g) with
3-bromo-1-trifluoromethylbenzene (22.5 g, 0.1 mol) in anhyd THF
(100 mL) was added CuI (0.2 g, 0.001 mol) at 10 °C, followed by
slow addition of 1 (20 g, 0.11 mol). The reaction mixture was then
1,1,1,3,3,3-Hexafluoro-2-(methoxymethyl)propane-2-ol (4a)
Compound 4a was prepared similarly. Reaction condition, the ratio
of reagents, analytical and spectroscopic data for 4a are given in
Synthesis 2002, No. 15, 2225–2231 ISSN 0039-7881 © Thieme Stuttgart · New York

PAPER
Ring Opening Reactions of 2,2-Bis(trifluoromethyl)oxirane
2231
brought to r.t. After 12 h, it was diluted with aq sat. solution of
NH4Cl (300 mL), and extracted with CH2Cl2 (100 mL). The organic
layer was dried (MgSO4), the solvent was removed under vacuum
and the residue (30 g) was distilled to give 17.2 g (53%) of 13a; bp
88–89 °C/13 mm Hg (Table 2).
References
(1) Publication No.: 8286.
(2) (a) Chiba, T.; Hung, R. J.; Yamada, S.; Trinque, B.;
Yamachika, M.; Brodsky, C.; Patterson, K.; Hayden, V.;
Jaminson, A.; Lin, S.-H.; Somervell, M.; Byers, J.; Coneley,
W.; Willson, G. J. Photopolym. Sci. Technol. 2000, 13, 657.
(b) French, R. H.; Feldman, J.; Zumsteg, F. C.; Crawford, M.
K.; Feiring, A. E.; Petrov, V. A.; Schadt, F. L. III; Wheland,
R. C. Semiconductor Fabtech, 14th Ed., 167; ICG
Publishing Ltd.: London, 2001.
Anal. Calcd for C11H7F9O: C, 40.51, H, 2.16, F, 54.42. Found: C,
40.64, H, 2.18, F, 54.32.
Compounds 12, 13a,b
These compounds were prepared similarly (Tables 1 and 2).
(3) Krespan, C. G.; Middleton, W. J. Fluorine Chem. Rev. 1967,
1, 145.
Reaction of 1 with Hexafluoroacetone; 2,2,4,4-Tetrakis(tri-
fluoromethyl)-1,3-dioxolane (14)
(4) (a) Burton, D. J.; Morken, P. A. In Methods of Organic
Chemistry (Houben–Weyl), Vol. E10b/1; Baasner, B.;
Hagemann, H.; Tatlow, J. C., Eds.; Thieme: Stuttgart, 2000,
Chap. 2.1.1.3, 483. (b) Furin, G. G. In Methods of Organic
Chemistry (Houben-Weyl), Vol. E10b/1; Baasner, B.;
Hagemann, H.; Tatlow, J. C., Eds.; Thieme: Stuttgart, 2000,
Chap. 2.1.1.1, 402. (c) For a review on application of
fluoroalkylsilanes in organic synthesis, see: Prakash, G. K.
S.; Yudin, A. K. Chem. Rev. 1997, 97, 757.
(5) For reviews on the chemistry of trifluoromethyloxirane,
see: (a) Katagiri, T. In Enantiocontrolled Synthesis of
Fluoro-Organic Compounds; Soloshonok, V., Ed.; Wiley:
New York, 1999, Chap. 5, 161. (b) Katagiri, T.; Uneyama,
K. J. Fluorine Chem. 2000, 105, 285.
(6) Dear, R. E. A.; Gilbert, E. E. (Allied Corporation) US Patent
3573330, 1971; Chem. Abstr. 1971, 74, 141498.
(7) Simmons, H. E.; Wiley, D. W. J. Am. Chem. Soc. 1960, 82,
2288.
(8) Chang, I. S.; Willis, C. J. Can. J. Chem. 1977, 55, 2465.
(9) Petrov, V. A.; Feiring, A. E.; Feldmann, J. (to DuPont) WO
00/66575, PCT/US/00/11746, 2000; Chem. Abstr. 2000,
133, 350691.
CsF (9 g, 0.06 mol) was dried at 120 °C at reduced pressure (>0.1
mm Hg) in a 250 mL 3-neck round-bottom flask for 2 h. Anhyd
MeCN (100 mL) was introduced under N2 at r.t. into the reaction
vessel and gaseous hexafluoroacetone (8 g, 0.047 mol) was intro-
duced into the flask at 25–30 °C. The epoxide 1 was added to the
resulting homogeneous solution dropwise ( 20 min) and the mix-
ture was stirred at r.t. for 12 h. It was diluted with H2O (200 mL),
the organic layer was separated, washed with H2O (2 50mL),
dried (MgSO4) and fractionated to give 4 g (23.5%) of 14; bp 70–
72 °C/760 mm Hg (Table 2).
+
MS: m/z = 346 [M+, C7H2F6O2 ].
Reactions of 1 with Electrophiles; 3,3,3-Trifluoro-2-hydroxy-2-
(trifluoromethyl)propyl Fluorosulfate (15a)
Compound 1 (36 g, 0.2 mol) was added slowly (exothermic!) under
stirring to HOSO2F (20 g, 0.2 mol) in a 50-mL glass flask at a rate,
which allow to maintain the internal temperature at 30–35 °C. The
reaction mixture was stirred for 30 min at 35–40 °C and was slowly
poured onto ice. The organic layer was separated, dried (MgSO4)
and distilled under reduced pressure to give 44 g (79%) of 15a; bp
72–74 °C/40 mm Hg (Table 2).
(10) Herrmann, W. A.; Eder, S. J. Chem. Ber. 1993, 126, 31.
(11) Howard, E. G.; Seargent, P. B.; Krespan, C. G. J. Am. Chem.
Soc. 1967, 89, 1422.
Compounds 15b, 16a,b
These compounds were prepared similarly (Tables 1 and 2).
(12) (a) Tarrant, P.; Allison, C. G.; Barthhold, K. P.; Stump, E. G.
Fluorine Chem. Rev. 1971, 5, 77. (b) Millauer, H.;
Schwertfeger, W.; Siegemund, G. Angew. Chem., Int. Ed.
Engl. 1985, 24, 161. (c) Knunyants, I. L.; Shokina, V. V.;
Tuyleneva, V. V.; Cheburkov, Yu. A.; Aronov, Yu. E. Izv.
Akad. Nauk SSR., Ser. Khim. 1966, 1831; Chem. Abstr.
1967, 66, 94673.
(13) Watts, R. O’B.; Tarrant, P. J. Fluorine Chem. 1975, 6, 481.
(14) Voronkov, M. G.; Baryshok, V. P.; Tandure, S. N.;
Vitkovskii, V. Y. U.; D’aykov, V. M.; Pestunovich, V. A. J.
Gen. Chem. USSR 1978, 48, 2033.
(15) Takshashi, O.; Furuhashi, K.; Fukumasa, M.; Hirai, T.
Tetrahedron Lett. 1990, 31, 7031.
(16) Ohno, F.; Kawashima, T.; Okazaki, R. Chem. Commun.
2001, 463.
(17) Grushin, V. V.; Marshall, W. J.; Halliday, G. A.; Davidson,
F.; Petrov, V. A. J. Fluorine Chem., in press.
(18) McBee, E. T.; Hathaway, C. E.; Roberts, C. W. J. Am. Chem.
Soc. 1956, 78, 3851.
3,3,3-Trifluoro-2-hydroxy-2-(trifluoromethyl)propyl Acetate
(2a)
A 400 mL Hastelloy shaker tube was charged with TaF5 (2 g, 0.007
mol), glacial AcOH (60 g, 1 mol) and 1 (180 g, 1 mol), evacuated at
–78 °C and kept for 12 h at 120 °C. The crude reaction product was
washed with H2O (300 mL), separated, dried (MgSO4) and distilled
to give 192–216 g (80–90%) of 2a; bp 75–76 °C/35 mm Hg (Lit.11
mp 78 °C/35 mm Hg).
1-(Trifluoromethyl)-4-[3,3,3-trifluoro-2-(trifluoromethyl)prop-
1-enyl]benzene (17b)
A mixture of 13b (10 g, 0.03 mol) and PCl5 (8.5 g, 0.04 mol) was
heated in a glass flask till evaluation of HCl had ceased ( 12 h). The
reaction mixture was quenched with cold water and stirred at 20–
50 °C for 1 h to reach the complete hydrolysis of POCl3. The sepa-
rated organic layer was dried (MgSO4) and distilled to give 6.7 g
(70%) of 17b; bp 76–78 °C/12 mm Hg (Table 2)
Anal. Calcd for C11H5F9: C, 42.88, H, 1.64, F, 55.49. Found: C,
42.66, H, 1.80, F, 55.30.
(19) Kolenko, I. P.; Filaykova, T. I.; Zapevalov, A. Ya.;
Mochalina, E. P.; German, L. S.; Polishcuk, V. R. Izv. Akad.
Nauk., Ser. Khim. 1979, 667; Chem. Abstr. 1979, 91, 38866.
(20) Dear, R. E. A. Synthesis 1970, 361.
(21) Dear, R. E. A.; Gilbert, E. E.; Murray, J. J. Tetrahedron
1971, 27, 3345.
Acknowledgements
The author thanks Dr. V. V. Grushin and Dr. A. F. Feiring for hel-
pful discussions, R. E. Smith Jr. for technical assistance and B. Vek-
ker for help with the preparation of the manuscript.
(22) Burton, D. J.; Inouye, Y. Tetahedron Lett. 1979, 20, 3397.
Synthesis 2002, No. 15, 2225–2231 ISSN 0039-7881 © Thieme Stuttgart · New York