Alcoholysis of fluoroform

Article abstract of DOI:10.1016/j.jfluchem.2014.06.006

Fluoroform (CHF₃) reacts with alkali metal alkoxides MOR (M = Na, K) in the corresponding alcohols ROH (R = Me, Et, i-Pr, t-Bu, and Allyl) at 80-120°C to give orthoformate esters HC(OR)₃ in 55-90% yield. Particularly notable is the f

Full text of DOI:10.1016/j.jfluchem.2014.06.006

Accepted Manuscript
Title: Alcoholysis of Fluoroform
Author: Fedor M. Miloserdov Vladimir V. Grushin
PII:
S0022-1139(14)00152-3
DOI:
Reference:
http://dx.doi.org/doi:10.1016/j.jfluchem.2014.06.006
FLUOR 8335
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2-6-2014
8-6-2014
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Alcoholysis of Fluoroform, Journal of Fluorine Chemistry (2014),
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*Graphical Abstract - Pictogram
CHF3 + 3NaOR
CH(OR)3 + 3NaF
80-120 oC
H
C
R = Me, Et, i-Pr,
t-Bu, Allyl
O
O
O
55-90% yield
Page 1 of 23

*Graphical Abstract - Synopsis
Fluoroform (CHF3) reacts with alkali metal alkoxides MOR (M = Na, K) in the corresponding
alcohols ROH (R = Me, Et, i-Pr, t-Bu, and Allyl) at 80-120 oC to give orthoformate esters
HC(OR)3 in 55-90% yield. Particularly notable is the formation of HC(OBu-t)3 in 75-80% yield
(62% isolated yield), an exotic organic compound that has been previously synthesized only once
(3% yield). Solutions of NaOH in ROH (R = Me, Et, i-Pr, t-Bu) react with CHF3 to give NaF,
HCOONa, and orthoformates HC(OR)3. Hydrolysis of fluoroform with MOH (M = Na, K) at
140 oC produces largely MF and HCOOM along with small quantities of CO.
Page 2 of 23

*Highlights (for review)
 CHF3 reacts with NaOR in ROH at 80-120 oC to give HC(OR)3 (55-90% yield).
 Extremely rare and exotic HC(OBu-t)3 forms in 75-80% yield (62% isolated yield).
 NaOH in ROH reacts with CHF3 to give NaF, HCOONa, and HC(OR)3.
-
 Alkaline hydrolysis of CHF3 produces F-, HCO2 , and small amounts of CO.
Page 3 of 23

*Manuscript
For the Special Issue of the Journal of Fluorine Chemistry, dedicated to Dr. Teruo Umemoto
Alcoholysis of Fluoroform
Fedor M. Miloserdov, Vladimir V. Grushin*
Institute of Chemical Research of Catalonia (ICIQ), Tarragona 43007, Spain
ABSTRACT
Fluoroform (CHF3) reacts with alkali metal alkoxides MOR (M = Na, K) in the corresponding
alcohols ROH (R = Me, Et, i-Pr, t-Bu, and Allyl) at 80-120 oC to give orthoformate esters
HC(OR)3 in 55-90% yield. Particularly notable is the formation of HC(OBu-t)3 in 75-80% yield
(62% isolated yield; X-ray), an exotic organic compound that has been previously synthesized
only once (3% yield). Solutions of NaOH in ROH (R = Me, Et, i-Pr, t-Bu) react with CHF3 to
give NaF, HCOONa, and orthoformates HC(OR)3. Hydrolysis of fluoroform with MOH (M =
Na, K) at 140 oC produces largely MF and HCOOM along with small quantities of CO.
Keywords:
Fluoroform
CHF3
HFC-23
Alcoholysis
Orthoformates
* Corresponding author at: Institute of Chemical Research of Catalonia (ICIQ), Tarragona
43007, Spain. E-mail address: vgrushin@iciq.es (V. V. Grushin).
1
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1. Introduction
Fluoroform (CHF3, trifluoromethane, HFC-23, R-23), a gas (b.p. -82 oC) and the lightest
member of the haloform family, was first reported by Meslans [1] and Chabrié [2] over 120
years ago. In the 1930’s, Henne [3] and Ruff et al. [4] developed efficient synthetic procedures
furnishing CHF3 in sufficient quantities for isolation in pure form and thorough studies.
Numerous experiments carried out back then, particularly by Henne [3], established that
fluoroform is an exceptionally chemically and biologically inert compound. In addition to being
nontoxic and highly unreactive, CHF3 is ozone-friendly and, consequently, is not on the
Montreal Protocol list of chemicals depleting the ozone layer. It is not surprising therefore, that
for many decades CHF3 was considered to be a rather unremarkable, nonhazardous compound.
As a result, large quantities of gaseous HFC-23 side-produced by the fluorochemicals and
fluoropolymers industries could be disposed of by venting into the atmosphere without much
environmental concern. This state of affairs, however, has recently changed dramatically.
In recent years, CHF3 has become a center of attention as a potent greenhouse gas with
the second highest global warming potential of 11,700 (100 years) and a long, 264-year
atmospheric lifetime [5-8]. The release of HFC-23 into the atmosphere should be stopped as
otherwise it would likely lead to an ecological disaster [9]. Therefore, the large quantities of the
side-generated fluoroform should be destroyed or utilized. As fluoroform currently lacks
industrial applications on a scale comparable with that of its production, the destruction of HFC-
23 is the only viable solution to the problem [5]. The available methods to eliminate large
quantities of fluoroform, a flame retardant, are thermal oxidation, catalytic hydrolysis, and
plasma destruction. All of these processes are costly and none of them are free from
considerable drawbacks.
2
Page 5 of 23

Utilizing HFC-23 waste streams as a chemical feedstock would provide an ideal solution
to the problem. However, the exceptional inertness of fluoroform makes its use as a reagent a
considerable challenge. This task is further complicated by the requirements of industrially
viable conditions and sufficiently low-cost chemicals and materials for converting CHF3 to
useful products on a scale commensurate with that of its side-production, ca. 20000-25000
metric tons annually. Since 1990’s, considerable progress has been made toward the
development of new chemical transformations of fluoroform. Strong bases have been
-
demonstrated to deprotonate CHF3, a weak acid (pKa = 27 in H2O) [10], to generate CF3
carbanion equivalents, e.g., for trifluoromethylation of carbonyl compounds and some other
electrophiles [11-23]. These reactions have been reviewed [24-26]. Over the last few years, a
novel approach to H-CF3 activation has emerged, employing transition metals [27-36]. Although
none of these reactions [11-36] have been commercialized for various reasons, some seem to
hold promise [22, 30-34, 36]. A number of high-temperature transformations of fluoroform have
also been developed, including the gas-phase flow pyrolysis to CF2=CF2 (TFE) and
hydrogenolysis to mixtures of hydrofluorocarbons (HFC’s) [37], the catalytic iodination to CF3I
[38, 39], and the co-pyrolysis with TFE yielding hexafluoropropylene [40] and with methane to
produce various fluorinated products [41-44].
In the current work, we studied reactions of fluoroform with simple bases such as NaOH
and KOH as well as with alkali metal alkoxides in the corresponding alcohols under mild
conditions. Surprisingly little has been reported on such reactions, although mineralization of
CHF3 with solid alkali metal hydroxides and alkali and alkaline earth metal carbonates at 200-
400 oC has recently been investigated in considerable detail [45].
3
Page 6 of 23

2. Results and Discussion
In their original publications on the synthesis of fluoroform, both Meslans [1] and
Chabrié [2] mentioned that CHF3 reacted with alcoholic KOH to give a mixture of potassium
fluoride and potassium formate (Fig. 1). Meslans conducted the hydrolysis in a sealed tube at
160 oC [1], whereas in Chabrié’s report, the reaction conditions were not specified [2]. In 1956,
Hine et al. published a detailed kinetic study of alkaline hydrolysis of six haloforms in 2:1
dioxane-water to determine the following order of reactivity CHBrClF >> CHBrCl2 > CHBr2Cl
≈ CHCl2I > CHBr3 > CHCl3 >> CHF3, also reporting that “the reaction of fluoroform was too
slow to measure” [46]. Hine’s observations are consistent with the fact that fluoroform is ca. 106
times less reactive than chloroform toward H/D exchange with aqueous alkali [10]. Very
recently, Thomoson and Dolbier [22] demonstrated that CHF3 reacts with KOH in aqueous
dioxane or acetonitrile in the presence of phenols or thiophenols to give ArOCF2H and
ArSCF2H, respectively. It was concluded that “The mechanism of the reaction almost certainly
involves the intermediacy of difluorocarbene, which would be formed by deprotonation of CHF3
by hydroxide followed by loss of fluoride ion” [22].
Fig. 1. The chemical equations for the reaction of CHF3 with KOH, exactly as they appear in the
original articles by Meslans [1] (1890; top) and Chabrié [2] (1892; bottom). Note the old symbol
“Fl” used for fluorine.
4
Page 7 of 23

We first confirmed that CHF3 reacted with NaOH or KOH under solvent-free conditions
to give the corresponding formate salt (Table 1, entries 1-3; Eq. (1)). These reactions were
carried out with freshly ground (in air) NaOH or KOH, in Fischer-Porter tubes at 140 oC under
initial CHF3 pressure of 50 psi (3.45 bar). The products were analyzed by 1H and 19F NMR,
using sodium acetate and sodium trifluoroacetate as internal standards for the aqueous phase and
1,3-benzodioxole and benzotrifluoride for the organic extracts (see the Experimental section for
details). With ca. 85% KOH (eutectic, m.p. = ca. 100 oC [47]), the reaction occurred in the melt,
whereas NaOH remained solid throughout the experiment and, therefore, agitation was
especially important for faster CHF3 hydrolysis with sodium hydroxide (Table 1, entries 1 and
3). After 65-75% conversion was reached at stirring, the reaction virtually stopped. It is
unlikely that considerably higher conversions could be achieved under such conditions because
as the reaction occurs, water is produced, diminishing the basicity and reactivity of the alkali in
the system. The yield of the formate anion (55-65%) was roughly 10% lower than that of
fluoride because of the competing reaction leading to CO (Eq. (2)), in accord with the literature
data [45]. The formation of CO was confirmed by GC analysis of the gas phase after the
reaction.
140 oC
CHF3 + 4MOH
M = Na, K
HCO2M + 3MF + 2H2O
(1)
140 oC
CHF3 + 3MOH
M = Na, K
CO + 3MF + 2H2O
(2)
5
Page 8 of 23

Table 1
Reactions of fluoroform with alkali metal hydroxides and alkoxides.a
Conversion
of base, %
Yield of
HC(OR)3
Entry Base (g)
Solvent (mL)
T, oC
HCO2M, % (yield, %)
1
NaOH (0.82)
-
140
140
140
120
120
120
80
75
65
30
60
45
50
55
75
90
55
90
80
85
60
65
55
20
2
KOH (1.32)
-
3 b
NaOH (0.82)
NaOH (0.82)
NaOH (0.82)
NaOH (0.82)
NaOH (0.82)
MeONa (1.08)
MeONa (1.08)
EtONa (1.36)
i-PrONa (1.64) c
t-BuONa (1.92)
t-BuOK (2.24)
-
4
MeOH (1.5)
EtOH (1.5)
i-PrOH (1.5)
t-BuOH (5.0)
MeOH (1.5)
diglyme (1.5)
EtOH (1.5)
i-PrOH (5.0)
t-BuOH (5.0)
t-BuOH (5.0)
35
15
40
50
CH(OMe)3 (15)
5
CH(OEt)3 (20)
6
CH(OPr-i)3 (10)
CH(OBu-t)3 (<0.5)
CH(OMe)3 (55)
CH(OMe)3 (70)
CH(OEt)3 (55)
7
8
120
120
120
120
80
9
10
11
12
13
14
CH(OPr-i)3 (90)
CH(OBu-t)3 (80)
CH(OBu-t)3 (75)
CH(OCH2CH=CH2)3 (60)
80
CH2=CHCH2ONa (1.60) c CH2=CHCH2OH (5.0)
120
a Reaction conditions: base (20 mmol), CHF3 (initial pressure 50 psi), 90-mL Fisher-Porter tube, 24 h. All yields are NMR yields
b
(±5%) calculated using Eqs. (1-3) on the total amount of base used for the reaction (see the Experimental section for details).
Without agitation. Generated in situ by adding 0.8 g of NaH (60% suspension in mineral oil) to the specified amount of the
c
corresponding alcohol.
6
Page 9 of 23

We then studied reactions of fluoroform with NaOH in various alcohols, ROH (Table 1,
entries 4-7). These reactions occurred in the temperature range of 80-120 oC to give NaF,
HCO2Na, and the corresponding orthoformate HC(OR)3 as a result of a competition between the
two processes shown in Eq. (1) and Eq. (3). We are unaware of publications reporting the
formation of orthoformates from fluoroform, although the reaction of chloroform with alkali
metal alkoxides is widely used to prepare the corresponding orthoformate esters [48]. The
conversion of the base did not exceed 45-60%, with the yield of the orthoformate decreasing in
the order R = Et (20%) > Me (15%) > i-Pr (10%) > t-Bu (<0.5%). The formation of small
quantities of the corresponding CHF2(OR) (ca. 0.5%) was observed in all of these reactions.
80-120 oC
CHF3 + 3NaOH + 3ROH
HC(OR)3 + 3NaF + 3H2O
(3)
R = Me, Et, i-Pr, t-Bu
Orthoformates are valuable reagents that find numerous applications in organic synthesis
[48]. To favor the formation of orthoformates from fluoroform, NaOH was replaced with alkali
metal alkoxides under anhydrous conditions (Table 1, entries 8-14; Eq. (4)). With MeONa in
MeOH (entry 8), the reaction gave HC(OMe)3 in 55% yield, along with 75% of NaF. Although
the yield of methyl orthoformate increased to 70% at ca. 90% conversion in diglyme (entry 9),
C2 products (MeO)2C=C(OMe)2 (ca. 2%) and (MeO)3C-CH(OMe)2 (ca. 10%) were detected by
GC-MS in the reaction mixture. This is apparently because the slower formation of HC(OMe)3
at the lower overall concentration of MeOX (X = Na, H) favored dimerization of the carbene
intermediates.
7
Page 10 of 23

80-120 oC
CHF3 + 3NaOR
HC(OR)3 + 3NaF
(4)
R = Me, Et, i-Pr, t-Bu, CH2=CH-CH2
The reactions of EtONa and i-PrONa in the corresponding alcohols furnished the
corresponding orthoformate esters in 55% and 90% yield, respectively (entries 10 and 11).
Likewise, allyl orthoformate was produced in 60% yield under similar conditions (entry 14). Of
special interest, however, is the reaction of fluoroform with t-BuOM (M = Na, K) in t-BuOH
(entries 12 and 13). These reactions afforded, in 75-80% yield, tri-tert-butyl orthoformate
HC(OBu-t)3, a simple yet exceedingly rare and exotic compound. This bulkiest orthoformate
ester has appeared only once in the chemical literature. In 1969, Hine et al. [49] reported the
synthesis and isolation of HC(OBu-t)3 in only 3% yield from the reaction of CHFCl2 with t-
BuOK in t-BuOH. In their article, Hine, Dalsin, and Schreck also noted that “in the preparation
of orthoformates from haloforms and alkali metal alkoxides, dichlorofluoromethane is the
haloform of choice” and that “fluoroform is relatively unreactive” under such conditions [49].
As can be seen from our results (entries 12 and 13), fluoroform can be successfully used to
produce HC(OBu-t)3 in >75% yield. In a scale-up of the reaction of CHF3 with t-BuONa (0.1
mol) in tert-butanol, NMR-spectroscopically pure HC(OBu-t)3 was isolated in 62% yield as a
white, low-melting (m.p. 25-26 oC [49]) crystalline solid. The structure of HC(OBu-t)3 was
confirmed by a single crystal diffraction study (Fig. 2) [50]. Also interesting is the fact that in all
our reactions of ROM/ROH with CHF3, the corresponding difluoromethyl ethers CHF2OR were
formed in only small amounts (0.5-1.5%), whereas similar transformations of haloforms bearing
two fluorine atoms have been reported to conventionally produce large quantities of such
difluoromethyl ethers [51-53].
8
Page 11 of 23

Fig. 2. ORTEP drawing of HC(OBu-t)3 with thermal ellipsoids drawn at the 50% probability
level. Selected bond distances (Å) and angles (o): O1-C1 1.390(5), O2-C1 1.399(5), O3-C1
1.398(5), O1-C1-O2 108.1(3), O1-C1-O3 107.4(3), O2-C1-O3 106.8(3).
We also probed the reactivity of CHF3 toward Mg(OEt)2 and Al(OPr-i)3 with CHF3 in
EtOH and i-PrOH, respectively. At temperatures up to 120 oC, no reaction was observed with
these much less basic alkoxides. On the other hand, the pyrrolide anion generated from pyrrole
and NaH reacted with fluoroform at 120 oC to give NaF (30%), three isomers of HC(C4H4N)3 in
a 5:3:2 ratio, and ca. 1% of (C4H4N)CHF2 (one isomer), as detected by GC-MS.
The reactions described above likely involve the intermediacy of difluorocarbene CF2
[49, 51-54]. A plausible mechanism for the formation of HC(OR)3 as the main product and of
the small quantities of CHF2OR is presented in Scheme 1. It is conceivable that the CF(OR)
carbene proposed by Hine [51-53] is converted to C(OR)2 that, as has been shown by Moss et al.
for R = Me [55], readily reacts with ROH to give HC(OR)3. The difluoromethyl ethers CHF2OR
9
Page 12 of 23

produced in only 0.2-1.5% yield in the reactions, are most likely end products rather than
intermediates in the formation of the orthoformates [52].
Scheme 1. Proposed mechanism for the formation of orthoformate esters from CHF3.
3. Conclusions
In this work, we have confirmed that, in full accord with the original early 1890’s reports
by Meslans [1] and Chabrié [2], fluoroform reacts with NaOH or KOH at 140 oC to give
mixtures of the corresponding metal fluoride and formate. Solutions of NaOH in various
alcohols ROH (R = Me, Et, i-Pr, t-Bu) also hydrolyze CHF3 to NaF and HCOONa. Importantly,
however, the corresponding orthoformate (up to 20%) is also produced in these reactions.
Against previously reported observations [49, 51-53], fluoroform can be sufficiently reactive
toward MOR (M = Na, K) in ROH (R = Me, Et, i-Pr, t-Bu, and Allyl) to give the corresponding
orthoformate esters in 55-90% yield, provided the reactions are carried out at 80-120 oC. Of
particular interest is the formation of HC(OBu-t)3 (70-80% yield), a simple yet extremely rare
and poorly accessible organic compound that has been previously synthesized only once and in
only 3% yield. A scale-up of the reaction of CHF3 with t-BuONa (0.1 mol) in tert-butanol
produced pure HC(OBu-t)3 that has been isolated in 62% yield and structurally characterized. It
is hoped that the overall simple, low-cost transformations developed in the current work may
contribute to a solution for the HFC-23 ecological problem.
10
Page 13 of 23

4. Experimental
Chemicals were purchased from Aldrich (EtONa, t-BuONa, (EtO)2Mg, (i-PrO)3Al,
pyrrole, allyl alcohol, CF3CO2Na, 1,3-benzodioxole, PhCF3), Alfa Aesar (MeONa, t-BuOK, t-
BuOH, CH3CO2Na), Acros (NaH, 60% suspension in mineral oil), Apollo Scientific (CHF3),
Panreac (NaOH, 98%), and Carlo Erba (KOH, 85%). Methanol, ethanol, isopropanol, tert-
butanol, toluene, and pentane were used as received, unless otherwise noted. Anhydrous MeOH,
EtOH, i-PrOH, t-BuOH, allyl alcohol, and pyrrole were distilled from CaH2 under argon and
stored over freshly activated 4 Å molecular sieves in an argon glove-box. Sodium
1
trifluoroacetate was dried at 130 oC under vacuum (0.05 mmHg) and stored in the glovebox. H
and 19F NMR spectra were recorded on a Bruker Avance 400 Ultrashield NMR spectrometer.
1,3-Benzodioxole, benzotrifluoride, sodium acetate, and sodium trifluoroacetate were used as
internal standards for quantitative 1H and 19F (D1 = 5 s) NMR analysis. Agilent Technologies
7890A-5975C and 7890B instruments were used for GC-MS and GC-TCD analyses,
respectively.
Alkaline hydrolysis of CHF3 (Table 1, entries 1-3). A 90-mL Fisher-Porter tube containing a
Teflon-coated magnetic stirbar was charged, in air, with freshly ground alkali (20 mmol;
calculated on the MOH assay in the reagent used), evacuated, and pressurized with CHF3 to 50
psi. After 24 h of heating at 140 oC (oil bath; see Table 1 for specifics), the tube was allowed to
cool to room temperature and the gas phase was analyzed for CO by GC-TCD. To the contents
of the tube, were added water (100 mL), sodium acetate, and sodium trifluoroacetate as internal
standards (Table 2). A ca. 0.6-mL aliquot of the resultant aqueous solution was admixed with
-
D2O (0.1 mL) and quantitatively analyzed by 1H (for HCO2 ) and 19F (for F-) NMR (see Tables 1
11
Page 14 of 23

and 2). The amount of the base consumed in the reaction was calculated using the stoichiometry
-
displayed in Eq. (1) and Eq. (2), as a sum of the amounts of the F- and HCO2 produced.
Reactions of CHF3 with NaOH in alcohols (Table 1, entries 4-7). A 90-mL Fisher-Porter tube
containing a Teflon-coated magnetic stirbar was charged in air with freshly ground NaOH (98%
purity; 0.82 g; 20 mmol) and an alcohol (see Table 1 for specifics), quickly evacuated, and
pressurized with CHF3 to 50 psi. After 24 h of agitation at 80 oC or 120 oC (oil bath; see Table
1), the tube was allowed to cool to room temperature, unsealed, and its contents were treated
with toluene (40 mL) containing 1,3-benzodioxole (200 L; 237 mg) and benzotrifluoride (50
L; 58 mg) as internal standards. Upon agitation, a solid inorganic phase and a liquid organic
phase were produced. A ca. 0.6-mL aliquot of the organic phase was filtered through Celite and
the filtrate was admixed with C6D6 (0.1 mL) and analyzed, within an hour, first by 1H and 19F
NMR and then by GC-MS. (A longer delay in carrying out the analysis may produce incorrect
data because of partial slow hydrolysis of the orthoformate product with residual moisture in the
toluene solvent and in the atmosphere). The solid inorganic phase was separated by filtration,
washed with toluene (3 × 15 mL), and dissolved in water (200 mL). Sodium acetate and sodium
trifluoroacetate were added as internal standards. A ca. 0.6-mL aliquot of this aqueous solution
was admixed with D2O (0.1 mL) and quantitatively analyzed by 1H and 19F NMR (see Tables 1
and 2). The amount of the base consumed in the reaction was calculated using the stoichiometry
-
displayed in Eq. (1) and Eq. (3), as a sum of the amounts of the F- and HCO2 produced.
Reactions of CHF3 with MOR in alcohols (Table 1, entries 8, 10, 12, and 13). A 90-mL
Fisher-Porter tube containing a Teflon-coated magnetic stirbar was charged, in a glovebox, with
12
Page 15 of 23

a metal alkoxide (20 mmol) and the corresponding anhydrous alcohol (see Table 1 for specifics),
brought out, quickly evacuated, and pressurized with CHF3 to 50 psi. After 24 h of agitation at
80 oC or 120 oC (oil bath; see Table 1), the tube was allowed to cool to room temperature,
unsealed, and its contents were treated with toluene (40 mL) containing 1,3-benzodioxole (200
L; 237 mg) and benzotrifluoride (50 L; 58 mg) as internal standards. A ca. 0.6-mL aliquot of
the resultant suspension was filtered through Celite and the filtrate was admixed with C6D6 (0.1
mL) and analyzed, within an hour, first by 1H and 19F NMR and then by GC-MS. (A longer
delay in carrying out the analysis may produce incorrect data because of partial slow hydrolysis
of the orthoformate product with residual moisture in the toluene solvent and in the atmosphere).
To the rest of the reaction mixture, were added water (200 mL) and sodium trifluoroacetate as an
internal standard. A ca. 0.6-mL aliquot of this aqueous solution was admixed with D2O (0.1 mL)
and quantitatively analyzed by 1H and 19F NMR (see Tables 1 and 2).
Reactions of CHF3 with NaOR generated in situ from NaH in ROH (Table 1, entries 11 and
14). A 90-mL Fisher-Porter tube containing a Teflon-coated magnetic stirbar was charged, in a
glovebox, with NaH (60% suspension in mineral oil; 0.80 g; 20 mmol) and anhydrous i-PrOH or
allyl alcohol (see Table 1 for specifics) and brought out. After stirring for 30 min at 120 oC (oil
bath), the tube was cooled to room temperature, quickly evacuated, and pressurized with CHF3 to
50 psi. After 24 of agitation at 120 oC (oil bath; see Table 1), the tube was allowed to cool to
room temperature, unsealed, and its contents were treated with toluene (40 mL) containing 1,3-
benzodioxole (200 L; 237 mg) and benzotrifluoride (50 L; 58 mg) as internal standards. A ca.
0.6-mL aliquot of the resultant suspension was filtered through Celite and the filtrate was
admixed with C6D6 (0.1 mL) and analyzed, within an hour, first by 1H and 19F NMR and then by
13
Page 16 of 23

GC-MS. (A longer delay in carrying out the analysis may produce incorrect data because of
partial slow hydrolysis of the orthoformate product with residual moisture in the toluene solvent
and in the atmosphere). To the rest of the reaction mixture, were added water (200 mL) and
sodium trifluoroacetate as an internal standard. A ca. 0.6-mL aliquot of this aqueous solution
was admixed with D2O (0.1 mL) and quantitatively analyzed by 1H and 19F NMR (see Tables 1
and 2).
Preparation of HC(OBu-t)3. A 450-mL Fisher-Porter bottle containing a Teflon-coated
magnetic stirbar was charged, in a glovebox, with t-BuONa (9.60 g; 100 mmol) and t-BuOH (25
mL), brought out, quickly evacuated, and pressurized with CHF3 to 50 psi. After 21 h of
agitation at 80 oC (oil bath), the bottle was allowed to cool to room temperature and opened to
air. Pentane (60 mL) was added and the mixture was transferred to a 250-mL flask. The bottle
was rinsed with pentane (3 × 30 mL) and the combined reaction mixture and the washings were
evaporated on a rotary evaporator to remove the pentane and t-BuOH. Vacuum transfer of the
residue at ca. 0.06 mmHg with gentle heating, followed by drying on a rotary evaporator (ca. 50
mbar at 40 oC for 1 h) gave 4.81 g (62%) of HC(OBu-t)3 as a colorless liquid that crystallized on
1
cooling to +8 oC. The compound was spectroscopically pure. H NMR (dry CDCl3), δ: 1.27 (s,
27H), 5.67 (s, 1H) [49]. 13C NMR (dry CDCl3), δ: 29.5, 73.7, 104.4.
14
Page 17 of 23

Table 2
NMR data for compounds obtained and for internal standards (in reaction mixtures).
Compound
1H NMR, δ
19F NMR, δ
1,3-benzodioxole
CH(OMe)3
5.45 (s, 2H), 6.70-6.79 (m, 4H)
3.25 (s, 9H), 4.91 (s, 1H)
-
-
CH(OEt)3
1.24 (t, J = 7 Hz, 9H), 3.63 (q, J = 7 Hz, 6H), 5.18 (s, 1H)
-
CH(OPr-i)3
CH(OBu-t)3
CH(Oallyl)3
CH3CO2Na
HCO2Na
1.27 (d, J = 6 Hz, 18H), 4.07 (sept, J = 6 Hz, 3H), 5.39 (s, 1H)
-
-
-
-
1.37 (s, 27H), 5.78 (s, 1H)
4.12 (m, 6H), 5.15 (m), a 5.25-5.50 (m), a 5.92 (m, 3H)
1.90
8.44
PhCF3
-
-63.7
CHF2OMe
CHF2OEt
5.74 (t, JF,H = 75 Hz)
5.82 (t, JF,H = 75 Hz)
5.89 (t, JF,H = 76 Hz)
6.05 (t, JF,H = 77 Hz)
-87.5 (d, JF,H = 75 Hz)
-84.7 (d, JF,H = 75 Hz)
-81.7 (d, JF,H = 76 Hz)
-77.3 (d, JF,H = 77 Hz)
-84.9 (d, JF,H = 75 Hz)
CHF2OPr-i
CHF2OBu-t
CHF2Oallyl
b
-
b
-
-89.1 (d, JF,H = 62 Hz)
CF3CO2Na
F-
-
-
-75.5
-120.1
a
Signals overlapped with those from the residual allyl alcohol. b Although the 1H NMR signals
could not be observed because of their low intensity and overlap with other resonances, the
presence of these products was confirmed by 19F NMR and GC-MS.
15
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Acknowledgments
We thank Drs. Jordi Benet Buchholz and Eddy Martin for the crystallographic study of
HC(OBu-t)3. This work was supported by the ICIQ Foundation and the Spanish Government
(Grant CTQ2011-25418). F.M. thanks the Government of Spain (MICINN) for the FPI PhD
Scholarship (BES-2012-054922). Dr. Carolina Gimbert-Suriñach’s assistance with the GC-TCD
analysis is thankfully acknowledged.
16
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