Convenient access to trifluoromethanol

Article abstract of DOI:10.1002/anie.200701823

From chimera to useful reagent: Easy access to trifluoromethanol in a one-step reaction from readily available inexpensive bulk chemicals opens the door for CF₃OH to become a useful general reagent in synthetic chemistry and industrial applications. (Graph Presented).

Full text of DOI:10.1002/anie.200701823

Angewandte
Chemie
DOI: 10.1002/anie.200701823
Perfluorinated Compounds
Convenient Access to Trifluoromethanol**
Karl O. Christe,* Joachim Hegge, Berthold Hoge, and Ralf Haiges
Dedicated to Professor George Olah on the occasion of his 80th birthday
With the exception of cyclo-C4F7OH,[1] alcohols possessing a
fluorine atom on the a-carbon atom are unstable and undergo
facile HF elimination.Therefore, it is not surprising that the
most simple perfluorinated alcohol, trifluoromethanol
(CF3OH), was synthesized by Seppelt only in 1977.[2] His
synthesis of CF3OH involved the reaction of a positively and a
negatively polarized chlorine ligand at ꢀ1208C [Eq.(1)].
Equation (2) constitutes a direct polar addition of HF
across the C O bond with the d+ hydrogen and the
=
dꢀ fluorine atoms of HF adding to the dꢀ oxygen and
d+ carbon atoms of the carbonyl group, respectively.Such
addition reactions are well known.For example, Olah and
=
Pavlath reported in 1953 that HFadds across the C O bond of
formaldehyde, but were unable to isolate and characterize the
pure monofluoromethanol.[9] In subsequent papers, Olah and
Mateescu[10] and Minkwitz et al.[11] successfully stabilized this
alcohol by protonation in super acids and identified the
CF3OCl þ HCl ! CF3OH þ Cl2
ð1Þ
+
resulting FCH2OH2 ion in solution by multinuclear NMR
The fact that the thermally unstable CF3OCl is not readily
available and had to be prepared from ClF and Cs+[CF3O]ꢀ,
which in turn had to be prepared from CsF and COF2,
discouraged further synthetic work with this interesting
compound.In spite of great academic and commercial
interest in -OCF3 substituted compounds, these have been
prepared exclusively by relatively cumbersome methods, such
as the replacement of the doubly bonded oxygen atom in acyl
fluorides by SF4 or halogen-exchange reactions using HF at
elevated temperatures and pressures and long reaction
times.[3] A literature survey showed that out of 128 citations
found by SciFinder for CF3OH, only the original synthesis
reports,[2] an unsuccessful attempt to protonate CF3OH in HF/
SbF5,[4] a measurement of its UV spectrum,[5] and a study of its
photoionization[6] involved the actual bulk synthesis or
handling of CF3OH.Therefore, it was of great interest to
find a more convenient access to this interesting compound to
make it readily available for general syntheses.
During a previous study we found that an excess of COF2
reacts with the strong Lewis acids SbF5 and AsF5 to form
oxygen-bridged, donor–acceptor adducts.[7,8] However, when
anhydrous HF was used as a solvent in these reactions, very
different products were obtained.This surprising result
prompted us to study the interaction of anhydrous HF with
COF2 in more detail.It was found that anhydrous HF and
COF2 are in equilibrium with CF3OH [Eq.(2)].
spectroscopy.Similarly, Andreades and England successfully
=
added HF across the C O bond of hexafluorocyclobuta-
none.[1]
We have studied the equilibrium in Equation (2) by
variable-temperature 19F NMR spectroscopy.In the temper-
ature range from ꢀ45 to 258C the percentage of CF3OH
increased from about 21% at ꢀ458C to a maximum of about
33% at ꢀ58C and then dropped off again rather sharply to
about 20% at 258C (Figure 1).This kind of temperature
dependence was rather unexpected because the unimolecular
dissociation of CF3OH to COF2 and HF has been calculated
to be endothermic (DH ꢁ 7 kcalmolꢀ1),[12] and, therefore, the
formation of CF3OH should be favored by a decrease in
temperature.The shape of the temperature-dependence
curve of Equation (2) implies that more than one equilibrium
reaction is involved.A plausible explanation for the observed
curve shape is that the concentration of monomeric HF is also
governed by a temperature-dependent equilibrium between
monomeric and oligomeric HF [Eq.(3)].
K2
n HF
ðHFÞ
H
ð3Þ
G
n
K1
COF þ HF
CF OH
H
ð2Þ
G
2
3
[*] Prof. Dr. K. O. Christe, Dr. J. Hegge, Dr. B. Hoge,[#] Dr. R. Haiges
Loker Research Institute and Department of Chemistry
University of Southern California
Los Angeles, CA 90089-1661 (USA)
Fax: (+1)213-740-6679
E-mail: kchriste@usc.edu
[#] Present address: Institut für anorganische Chemie
Universität Köln (Germany)
[**] This work was funded by the Air Force Office of Scientific Research,
the Office of NavalResearch, Merck KGaA, and the NationalScience
Foundation under Grant No. 0456343. We thank Dr. J. Sheehy for
some of the calculations.
Figure 1. Temperature dependence of the COF2 +HFÐCF3OH equilib-
rium measured by area integration of the corresponding 19F NMR
signals for two different mole ratios of HF/COF2.
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It is well known that HF forms oligomeric ring and chain
A second major issue was the determination of the exact
nature of the CF3OH species present in liquid HF.Because
gaseous oligomeric HF is a stronger acid than monomeric
HF[14] or HN3,[15] HN3 is completely protonated in liquid HF
[Eq.(6)]. [16]
structures in the liquid phase, and even in the gas phase at
elevated pressures.[13] Combining Equations (2) and (3) shows
that the absolute concentration of CF3OH increases, as
expected, with increasing concentrations of COF2 and mono-
meric HF [Figure 2 and Eq.(4)] and that the mole ratio of
n HF þ HN3ꢀ+H2N3þHF2ꢀ ꢂ ðnꢀ2Þ HF
(
ð6Þ
sffiffiffiffiffiffiffiffiffiffiffiffiffiffiffi
½ðHFÞnŠ
n
ð4Þ
½CF3OHŠ ¼ K1½COF2Š½HFŠ ¼ K1½COF2Š
K2
Although the gas-phase acidity of CF3OH is somewhat
higher[17,18] than that of HN3, polymeric liquid HF is more
acidic than either monomeric HF or CF3OH (see Table 1).
Therefore, the possibility had to be considered that in liquid
HF trifluoromethanol might also be protonated.
CF3OH to COF2 increases with increasing dilution, and
decreases if K2 dominates at the lower temperatures [Eq.(4)].
Table 1: Observed (values listed with error bars) and calculated (values
listed without error bars) gas-phase acidities of CF3OH and related acids.
acid
DGo [kcalmolꢀ1
]
Ref.
(HF)3
HI
CF3OH
(HF)2
HCl328.10
HN3
304.0
[14]
[a]
309.3ꢃ0.2
323.0ꢃ1.6
326.1
[17]
[14]
[a]
ꢃ0.10
[a]
[a]
337.9ꢃ2.3
365.50 ꢃ0.2
HF
[a] Data from NIST Standard Reference Database 69, March 1998
Release: NIST Chemistry WebBook (data compiled by J. E. Bartmess).
Figure 2. Temperature dependence of the absolute concentrations of
CF3OH measured by area integration of the 19F NMR signals of HF
and CF3OH for two different mole ratios of HF/COF2.
This issue was settled by recording the 13C and 19F NMR
spectra of HF solutions of CF3OH and [CF3OH2]+[SbF6]ꢀ and
comparing them with those previously reported[2] for neat
CF3OH.It was found that the chemical shifts of all three
systems were, within experimental error, identical (see
Table 2).Because one would predict that on protonation of
CF3OH the carbon and the fluorine nuclei should become
more deshielded, the chemical shifts for these species were
calculated by theoretical methods (see Table 2).The calcu-
lated 19F chemical shifts were in excellent agreement with
those observed for neat CF3OH[2] and the closely related
species CF3OCH3 and [CF3O(CH3)2]+[19] and, indeed, pre-
dicted significant deshielding on protonation.The calculated
corresponding 13C chemical shifts for the trifuoromethyl
Therefore, the CF3OH/COF2 ratio is higher in dilute
solution, although the absolute CF3OH concentration
becomes lower.To a lesser extent, the CF 3OH concentration
is also influenced by the solubility of COF2 in liquid HF.To
minimize this effect, the NMR equilibrium measurements
were carried out with a large excess of COF2 and a minimum
of ullage above the liquid phase.
The reversal of the slope of the CF3OH concentration
curve at about ꢀ58C, accompanied by a sharp decline in
CF3OH concentration at higher temperatures is attributed to
the thermal decomposition of CF3OH[2] becoming the dom-
inating effect.On the basis of previous calculations, which
showed that the energy barrier for intramolecular HF
elimination is very high,[12] this decomposition is most likely
not unimolecular, but either involves a dimer or oligomer or is
catalyzed by traces of H2O,[12] HF, or active surfaces.The
equilibrium in Equation (2) was also approached from the
CF3OH side by treating Cs+CF3Oꢀ with a large excess of
liquid HF [Eq.(5)].
Table 2: Observed 19F and 13C NMR data for CF3OH and related
compounds. Values calculated at the MP2/6-311++G(2d,2p) level are
given in parentheses.
1
d
19F obsd (calcd)
d
13C obsd (calcd) J13C–19F
[ppm]
[ppm]
[Hz]
neat CF3OH[a]
CF3OH in HF
ꢀ54.5 (ꢀ59.9)
ꢀ57.8
118 (131.4)
120.4
116.8 (136.4)
256
254
277
CF3OH2+SbF6ꢀ in ꢀ58.4 (ꢀ41.1)
CsþCF3Oꢀ þ 2 HF ! CsþHF2ꢀ þ CF3OH
ð5Þ
HF
CF3OCH3
[b]
ꢀ65.6 (ꢀ68.3)
CF3 123.7 (132.6), 252.3
CH3 53.7 (56.3)
CF3 118.2 (132.5), 281
CH3 (78.9)
CF3 120.7 (132.8), 287.0
CH3 80.2 (81.0)
It was found that the equilibrium in Equation (2) was
rapidly established and the COF2/CF3OH ratio was compa-
rable to that obtained when it was approached from the
COF2/HF side.The experimental determination of individual
rate constants for the different equilibria was not feasible
because of the complexity of the system.
CF3OHCH3+SbF6
in HF
ꢀ63.7 (ꢀ59.1)
ꢀ
CF3O(CH3)2+SbF6 ꢀ66.9 (ꢀ67.9)
ꢀ
in HF[b]
[a] Data from reference [2]. [b] Data from reference [19].
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Angewandte
Chemie
groups of the unprotonated species were about 12 ꢃ 2 ppm
lower than those observed and also showed some, albeit
smaller, deshielding on protonation.
These findings presented a dilemma because either the
experimental or the calculated shifts had to be seriously
flawed and, therefore, it was impossible to decide on the basis
of the chemical shift data alone whether CF3OH in liquid HF
is protonated or not.Fortunately, the one-bond 13C-19F
In conclusion, the COF2 + HFÐCF3OH equilibrium pro-
vides a convenient one-step access to trifluoromethanol from
inexpensive and readily available bulk chemicals.It is
expected to transform CF3OH from an exotic laboratory
curiosity into a generally useful reagent of significant interest
for the syntheses of commercially interesting products.
coupling constants were found to be significantly different Experimental Section
Caution! Carbonyl fluoride is a toxic gas (24 h LC50 = 370 ppm)[20]
and should be handled with care.Anhydrous HF can cause severe
burns and contact with the skin must be avoided.
for CF3OH (1J13C,19F = 255 ꢃ 1 Hz) and CF3OH2 (1J13C,19F
=
+
277 ꢃ 1 Hz).This difference is in accord with our expectations
that on protonation, the covalent character and s-orbital
Materials and apparatus: All reactions were carried out in either
teflon-FEP NMR tubes or ampules that were closed by stainless steel
valves.Volatile materials were handled in a stainless steel/teflon-FEP
vacuum line.[21] All reaction vessels were passivated with ClF3 prior to
ꢀ
contribution to the C F bond should increase, resulting in
stronger coupling.Because the J13C,19F coupling constant for
1
CF3OH in liquid HF was observed to be 254 Hz, it can be
concluded that 1) CF3OH is not protonated in liquid HF and
2) coupling constants provide a much better criterion than
chemical shifts for distinguishing between protonated and
unprotonated species.Additional support for the conclusion
that CF3OH in HF solution is unprotonated comes from the
reaction of CsCF3O with HF.The formation of HF 2ꢀ as a by-
product in Equation (5) reduces the acidity of the HF solvent,
thereby rendering protonation of CF3OH less likely.In
agreement with the spectra of the neat CF3OH/COF2/HF
use.HF was dried by storage over BiF .[22] Carbonyl fluoride (PCR
5
Research Chemicals) was purified by fractional condensation prior to
use.The NMR spectra were recorded either on Varian Unity
300 MHz or Bruker AMX-500 NMR instruments by using 5-mm
variable-temperature broad-band probes and TMS and CFCl3 as
external references.The mole ratios of HF and CF 3OH were
determined by area integration of the corresponding NMR signals.
The absolute concentrations of CF3OH were determined by integra-
tion of the areas of the CF3OH and HF NMR signals and weighing of
the HF used.Nonvolatile materials were handled in the dry nitrogen
atmosphere of a glove box.
Preparation of solutions of CF3OH in HF: In a typical experi-
ment, anhydrous HF (3 mL) and COF2 (5 mmol) were condensed on
the vacuum line at ꢀ1968C into a prepassivated, 5-inch o.d. teflon-
FEP ampule, which was closed by a stainless steel valve.The mixture
was warmed to 08C and rapidly equilibrated to a solution containing
COF2 and CF3OH in a mole ratio of about 2.5:1. These solutions were
1
system, the J13C,19F coupling constant was observed to be
254 Hz.
Having demonstrated that CF2O and HF are in equilib-
rium with CF3OH with useful CF3OH concentrations as high
as 33 mol%, it remained to be shown that this equilibrium can
be exploited for synthetic purposes.Continuous removal of
CF3OH by reaction with a suitable reagent shifts the
equilibrium in Equation (2) all the way to the right and
allows trapping of the CF3OH in the form of useful
derivatives.We have demonstrated this approach by con-
version of the CF3OH into either trifluoromethyloxonium
stable at room temperature.Complete conversion of COF into
2
CF3OH could be achieved by the addition of a third component, such
as a strong Lewis acid or CH3F in the presence of a suitable catalyst,
which reacted quantitatively with the CF3OH and shifted the
COF2ÐCF3OH equilibrium all the way to the side of CF3OH.
Theoretical methods: Theoretical calculations were carried out
by using the B3LYP density functional method[23] and a 6-311 + +
G(2p,2d)[24] basis set.Optimized geometries and isotropic NMR
shieldings were calculated by the GIAO-MBPT(2) approach,[25]
which employs the gauge-including atomic orbital (GIAO) solution
to the gauge-invariance problem.[26] Chemical shifts were obtained by
referencing these shieldings to those of the standard reference
compounds TMS and CFCl3, which were computed at the same level
of theory.
ꢀ
MF6 (M = Sb or As) salts [see above and Eq.(7)] or ethers,
ꢀ
CF3OH þ HF þ MF5 ! CF3OH2þMF6
ð7Þ
such as CF3OCH3 (E143A), which are of significant interest as
potential chlorofluorocarbon replacements with low ozone
depletion potentials [Eq.(8)].
Received: April 25, 2007
Revised: June 16, 2007
Published online: July 10, 2007
CF3OH þ CH3F ! CF3OCH3 þ HF
ð8Þ
Keywords: alcohols · carbonyl fluoride · fluorine ·
hydrogen fluoride · trifluoromethanol
The syntheses of numerous higher a-fluoro alcohols and
the generality of the ether formation have also been
demonstrated in our laboratory, but are not included herein
because of the large amount of data and the space limitations.
In addition to the ether synthesis, the convenient access to
trifluoromethanol is expected to have also significant indus-
trial interest for other applications, such as trifluoromethoxy-
substituted compounds for pharmaceuticals and liquid-crystal
materials.[3] More details on the reaction chemistry of CF3OH,
the stability and barriers to HF elimination in fluoro alcohols,
and the syntheses of higher a-fluoro alcohols and their
reaction chemistry will be published in separate papers.
.
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