Direct fluorination of cyclic carbonates and closo-K2[B 12H12] in a slug-flow ministructured reactor

Article abstract of DOI:10.1002/cplu.201200267

A novel minireactor for direct fluorination of organic and inorganic substances was tested. The reactor consists of nickel-coated copper blocks with mechanically machined 1 mm channels and is equipped with an active cooling system. The direct fluorination of ethylene carbonate and propylene carbonate is described. For the fluorinated propylene carbonate, the NMR data of various fluorinated isomers were determined. The Gibbs reaction energies for the direct fluorination of ethylene and propylene carbonate were calculated at the reliable G3 level of theory. The excellent decomposition stability of the cyclic carbonates against high fluorine and HF concentrations also qualifies them as good solvents for direct fluorination processes, especially for ionic substrates. In this respect, the direct fluorination of the inorganic salt closo-K₂[B₁₂H₁₂] in cyclic carbonates is presented.

Full text of DOI:10.1002/cplu.201200267

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DOI: 10.1002/cplu.201200267
Direct Fluorination of Cyclic Carbonates and closo-
K2[B12H12] in a Slug-Flow Ministructured Reactor
Mathias Hill,[a] Patrick Baron,[a] Keith Cobry,[b] Sascha K. Goll,[a] Philipp Lang,[b]
Carsten Knapp,[c] Harald Scherer,[a] Peter Woias,[b] Pengcheng Zhang,[a] and Ingo Krossing*[a]
A novel minireactor for direct fluorination of organic and inor-
ganic substances was tested. The reactor consists of nickel-
coated copper blocks with mechanically machined 1 mm chan-
nels and is equipped with an active cooling system. The direct
fluorination of ethylene carbonate and propylene carbonate is
described. For the fluorinated propylene carbonate, the NMR
data of various fluorinated isomers were determined. The
Gibbs reaction energies for the direct fluorination of ethylene
and propylene carbonate were calculated at the reliable G3
level of theory. The excellent decomposition stability of the
cyclic carbonates against high fluorine and HF concentrations
also qualifies them as good solvents for direct fluorination pro-
cesses, especially for ionic substrates. In this respect, the direct
fluorination of the inorganic salt closo-K2[B12H12] in cyclic carbo-
nates is presented.
Introduction
Special applications often require
the bonding of fluorine atoms in
specific positions into a target
molecule.[1] Fluorine, with its very
high electronegativity and very
stable bonds, offers a multitude
of possibilities for application in
chemical industrial processes. For
example, fluorination is employed
to vary the lipophilicity in phar-
maceutical products. Today, ten of
the 30 top-selling pharmaceutical
are the enhancement of the polarity of liquid crystals for
LCDs,[4] the weakly coordinating anions[5] or the fine tuning of
the electrochemical stability of solvents for lithium-ion batter-
ies such as in (fluorinated) ethylene carbonate.[6]
In order to perform fluorination of organic compounds, ex-
pensive reagents, such as DAST, Selectfluor, or the Ruppert–
Prakash reagent are used.[7] Another commonly applied
method is electrofluorination, which works well for perfluorina-
tion but is rather limited in terms of selectivity and the toler-
ance of functional groups.[8–10] After the initial work by Adcock
and Lagow[11] and Rozen,[12] direct fluorination using F2 became
a real alternative and several groups successfully demonstrated
its application.[13,14] Nevertheless there are two main difficulties
that are commonly encountered when working with fluorine:
COVER
products contain at least one flu-
orine atom.[2,3] Other examples
[a] M. Hill, P. Baron, S. K. Goll, Dr. H. Scherer, P. Zhang, Prof. I. Krossing
Institut fꢀr Anorganische und Analytische Chemie
Freiburger Materialforschungszentrum FMF and
Freiburg Institute for Advanced Studies FRIAS
Albert-Ludwigs-Universitꢁt Freiburg
1) The strongly exothermic character of the reactions: for ex-
ample, CH4 +F2!CH3F+HF (DrHꢀꢁ430 kJmolꢁ1). A single
substitution already provides enough energy to cleave
a CꢁC bond in the molecule, which usually has a bond
energy of 351–368 kJmolꢁ1 [14]
The fast rate of the direct
.
Albertstrasse 21, 79104 Freiburg i. Br. (Germany)
Fax: (+49)761-203-6001
E-mail: krossing@uni-freiburg.de
fluorination reaction often leads to local hot spots or even
explosions,[15] which is problematic with respect to selectivi-
ty and degradation reactions, not to mention operational
safety. To overcome this, very fast energy transport and effi-
cient temperature control is essential.
[b] Dr. K. Cobry, Dr. P. Lang, Prof. P. Woias
Department of Microsystems Engineering (IMTEK)
Albert-Ludwigs-Universitꢁt Freiburg
Georges-Kçhler-Allee 102, 79110 Freiburg i. Br. (Germany)
[c] Prof. C. Knapp
2) The second challenge is the toxicity of fluorine. A leak can
lead to a release of highly toxic fluorine or hydrogen fluo-
ride gases. Thus, a minimization of hazardous reagents
would be desirable, given that the overall product yield is
still acceptable.
Fachbereich C, Anorganische Chemie
Bergische Universitꢁt Wuppertal
Gaußstrasse 20, 42097 Wuppertal (Germany)
Supporting information for this article is available on the WWW under
http://dx.doi.org/10.1002/cplu.201200267. It contains details of the en-
thalpy/Gibbs free energy calculation carried out at the G3 Level; the cal-
orimetric calculations; mass spectra of nonvolatile material after fluorina-
tion of toluene; selected NMR spectra; flow characterization results; pic-
ture of bubbles at the product outlet and graphs showing the values
listed in Table 4.
One elegant possibility to handle the problems of elemental
fluorine is the use of microstructured reactors. These reactors,
having reaction channels less than 1 mm in diameter, were
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used successfully for a variety of liquid organic chemical reac-
tions since the late 1990s.[16–21] Their high surface to volume
ratio provides very fast heat transfer, which is necessary to
remove the high thermal energy released during the direct flu-
orination of a substance.[22–26] In addition, the small channels
guarantee fast mixing in two-phase systems.[27] The risks of
working with fluorine are minimized because of the reduced
volumes.
Toluene
In the literature the direct fluorination of toluene in acetonitrile
was carried out in microreactors and is the most often de-
scribed model system. Besides the main products, de Mas
et al.[33] and Jꢁhnisch et al.[31] already reported on the formation
of high molecular side products.
Despite of these advantages, so far very few research
groups have developed microreactors for direct fluorinations.
Chambers, Sandford and co-workers developed channel and
falling film reactors and used them for various selective direct
fluorinations. Their reactors are based on nickel or stainless
steel, and are to date the only broadly tested microreactor sys-
tems for direct fluorination. They obtained very good results
for the selective direct fluorination of organic compounds such
as b-ketoesters,[28] aromatic systems,[29] and ethers.[30] Jꢁhnisch
et al.[31] developed a falling film micro reactor for direct fluori-
nation and Jensen and co-workers[32] invented a silicon-based
microreactor. The channel widths were between 500–250 mm.
Both groups tested their reactors with toluene in solvents like
acetonitrile as their only substrate.
Ethylene carbonate (EC)
The substitution of one of the four symmetry-equivalent hy-
drogen atoms in EC leads to a single possible product. Double
fluorination only leads to three new products. Its structures are
very stable against fluorine and a HF concerning fragmenta-
tion. Fluorine concentrations of 30% during direct fluorination
without solvent are standard in classical batch reactions.[15,34,35]
In addition, monofluorinated ethylene carbonate (F1-EC) is
used commercially as solvent additive in lithium-ion batteries
and is produced on a scale of a few tons per year, which
would be in the desired range for commercial production of
mini- or microreactors. Because pure ethylene carbonate has
a melting point of 368C, heating or a solvent is necessary. As
solvent the product F1-EC was used; please compare with ref-
erence [34]. Its melting point of 178C allowed experiments at
room temperature.
Herein, the direct fluorination of ethylene carbonate, propyl-
ene carbonate, and closo-K2[B12H12], using ministructured reac-
tors is described. With channel diameters of 1 mm, this mini-
reactor represents a proof-of-concept stepping stone toward
the future goal of true microreactors.
Propylene carbonate (PC)
By having an additional methyl group compared with ethylene
carbonate, the number of possible monofluorinated isomers
increases to four. Thus, the regioselectivity of the direct fluori-
nation can be determined. Propylene carbonate, like ethylene
carbonate, is remarkably stable against fluorine or hydrogen
fluoride, and is a liquid with a melting point of ꢁ558C. These
factors permitted experiments without solvent and at lower
temperatures. To the best of our knowledge only one group
has published a direct fluorination of propylene carbonate:
Nanbu et al. published a batch reaction, but did not give any
details on yield or optimization.[36] However, they investigated
the influence of the monofluorination on relative permittivity,
density, refractive index, and dynamic viscosity. As a conclusion
they expect the monofluorinated propylene carbonate to form
better conducting salt solutions than nonfluorinated propylene
carbonate.
Choice of substrates
A summary of the investigated reactions is shown in Figure 1.
The main substrates are the two cyclic carbonates (reactions A
and B) and closo-K2[B12H12] (reaction C). Nevertheless, we also
include a short critical comment on the direct fluorination of
toluene.
closo-K2[B12H12]2ꢁ
To our knowledge, no ionic substances and no boron clusters
have thus far been investigated for direct fluorination in mini/
microreactors. However, Strauss and co-workers published
a batch method for the direct fluorination of closo-K2[B12H12] to
give K2[B12F12].[37] The substrate salt K2[B12F12] and the products
are soluble in acetonitrile, which is helpful for fluorination in
mini/microstructured reactors. Moreover, similar related batch
reactions were reported to be susceptible to complete degra-
dation and formation of the thermodynamic sinks BF3 gas and
[BF4]ꢁ.[37] Because the halogenated dodecaborates can be used
Figure 1. Summary of the investigated direct fluorination reactions with
partly idealized outcome: (X) toluene; (A) ethylene carbonate; (B) propylene
carbonate; (C) closo-K2[B12H12].
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to stabilize for example, reactive cations or electrolyte salts in
lithium-ion batteries,[38] it appeared interesting to investigate
the fluorination of such an inorganic substrate in our minireac-
tor system.
Results and Discussion
Methods and Materials
Reactor
The reactor construction and design was performed in the
group of P. Woias and co-workers. Full details on the reactor
design and construction were published elsewhere.[39,40]
It was constructed from four nickel-coated (10–20 mm)
copper blocks. All channels and holes were conventionally ma-
chined. The meandered channels measure 1ꢂ1 mm in their
profile and have 908 corners. A top view of the channels is
shown in Figures 2 and 3. The reactor was designed for slug
Figure 4. Above: The minireactor before being assembled. Below: Construc-
tion scheme of the minireactor.
ate second fluorination of an already fluorinated molecule
would lead to a strongly increased risk of decomposition.
A potent heat sink was included and optimized for a maxi-
mum cooling at the point of the gas inlet. Five T-type thermo-
couple sensors were placed inside the reactor block at a dis-
tance of 1 mm from the reaction channels themselves. They
were placed 1, 2, 4, 29, and 53 cm behind the gas inlet. The
minireactor had a reaction channel length of 53.7 cm from the
junction of the gas inlet and the main reaction channel. The
channel length before the gas inlet was 6.6 cm. Figure 3 shows
the reactor before assembly.
Figure 2. Picture of a nitrogen and 2-propanol slug flow for flow characteri-
zation, showing the meandered channels, the liquid inlet, and the gas
nozzle.
Figure 3. Scheme showing the flows within a gas liquid slug flow system.
Fluorine delivery system
flow. The flow parameters, like slug flow length, velocities, fre-
quencies, and bubble surfaces were measured in experiments
using nitrogen and 2-propanol.[42] A picture of the experimen-
tal setup and representative slugs are shown in Figure 2 and 4.
The ranges of the slug flow regime were tested between 5
and 400 mLhꢁ1 liquid and gas flow (see Figure 2 and appen-
dix 3 in the Supporting Information). Below 25 mLhꢁ1 liquid
flows at a gas flow rate of 400 mLhꢁ1, and the slug flow
regime changes to an annular type flow. By changes to the
liquid flow the bubble length could be varied between 2 and
32 mm.
A 5 L cylinder of fluorine (99.98%; Solvay Fluor GmbH) was
used as a fluorine source. It was diluted to desired concentra-
tions by 99.996% nitrogen. All piping was constructed from
monel or perfluoroalkoxy polymer tubes. All connectors were
made from monel (Swagelok). To measure the fluorine pres-
sure, a fluorine compatible sensor (MKS Baratron) was used.
The flow and the dilution of the gases were controlled by two
mass flow meters (MKS M330). For mixing the nitrogen and
the fluorine stream, a monel T-shaped connector was used.
Before use, the system was carefully leak tested and passivated
for several hours using a gradually increasing fluorine concen-
tration, up to 100%.
Slug flow was chosen, because we expected a higher fluo-
rine conversion rate in comparison with annular flows. In addi-
tion, a current within the liquid slug is induced, which should
improve the exchange of substrate molecules at the phase
boundaries (Figure 4).[41] This current would lead to an im-
proved heat control and a reduced probability of multiple fluo-
rination on one molecule within a very short time. An immedi-
Liquid delivery system
A Masterflex 7730-00 peristaltic pump with 4 mm outer diame-
ter PFA (perfluoroalcoxy polymer) tubing and six rollers was
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n
ꢁ n
used to realize a cyclic system for the minireactor. The effluent
was repeatedly recycled back into the reactor after separating
the liquid from the remaining gaseous hydrogen fluoride and
nitrogen. A self-constructed small pulsation dampener was
placed between pump and the reactor inlet. For the toluene
experiments a syringe pump was used. However, this noncyclic
system yielded low conversions for the fluorination of toluene.
F1ECr
F1ECo
Space ꢁ TimeYield ¼
ꢂ 100
ð4Þ
ð5Þ
ð6Þ
Vreactionchannel
n
þ n
þ n
transF2EC
cisF2EC
4;4F2EC
YF2 ¼
CF2 ¼
ꢂ 100
nF
2
n
þ n
þ n
þ n
F1ECr
transF2EC
cisF2EC
4;4F2EC
ꢂ 100
nF
2
In Equations (1)–(6) nEC0 is the molar amount of ethylene car-
bonate before the reaction, nECr the amount after the reaction,
meanwhile nF1EC0 is the amount of F1EC added as solvent and
nF1ECr is the amount of F1EC found in the product mixture. See
Figure 5 for the structure of possible twice fluorinated ethyl-
ene carbonated isomers (F2EC).
Fluorination of toluene
It was possible to obtain monofluorinated toluene compounds
by direct fluorination of toluene in acetonitrile. With regard to
selectivity, the results were similar to those published by
de Mas et al. (Table 1), who used a microreactor with channel
diameter of less than 500 mm.
Table 1. Relative ratios of the four possible monofluorinated toluene
compounds. T=08C, 12.5 vol% toluene in acetonitrile, liquid flow=
90 mLhꢁ1, gas flow=480 mLhꢁ1, 25 vol% fluorine.[36]
Fluorination position
ortho
meta
para
methyl
this study
Jensen et al.[36]
3.4
3.7
1.0
1.0
2.0
2.1
0.9
–
Figure 5. Two 19F NMR spectra of EC after the fluorination reaction. Condi-
tions: F1EC (30 wt%) as solvent. Spectrum (a) 0.5 equiv F2, T=228C, liquid
flow=2.5 mLminꢁ1 gas flow=6.6 mLminꢁ1, 45 vol% F2. Spectrum
A deeper investigation of this system was not carried out,
because of difficulties, which were occurring when toluene
and acetonitrile were fluorinated. Both substances tended to
form solid organic material, leading to a clogging of the reac-
tor, after 1–3 hours of use. A mass spectrometry analysis (EI,
2008C, 70 eV, 500 mA) of the dark organic material collected
inside the reactor showed masses up to 532 m/z (see the Sup-
porting Information). Evident were masses that indicated the
formation of toluene di- and trimers. This is an indicative for
the formation of less soluble or even solid toluene oligomers.
The formation of such low-solubility materials, which led to
blockages inside the reactor, makes the fluorination of toluene
a difficult reaction for direct fluorination in microreactors and
we recommend using other substrates for testing purposes.
(b) 0.5 equiv F2, T=228C, liquid flow=2.5 mLminꢁ1, gas flow=3.4 mLminꢁ1
,
88 vol% F2, minireactor. The [BF4]ꢁ signal is formed from residual HF.
Our aim at fluorinating ethylene carbonate (reaction A in
Figure 1) was to achieve a high yield of the commercially inter-
esting F1EC. Therefore, a high conversion and a limited genera-
tion of difluorinated ethylene carbonates were desirable. To
reach the desired high conversion, the fluorine should react
completely with ethylene carbonate without causing fragmen-
tation. As ethylene carbonate is a solid at room temperature,
liquid monofluorinated ethylene carbonate was added as a sol-
vent.[34] Adding the product as the solvent has the advantage
of reducing the number of possible active reagents and allows
for a straightforward separation of the products. However, the
selectivity with respect to doubly fluorinated products (F2EC) is
lowered, yet all concentrations of F1EC below 25 wt% led to
crystallization of ethylene carbonate at room temperature. In
our experimental setup the PFA tubing could not be heated
and thus we had to tolerate this relatively high content of F1EC
and the consequent losses in selectivity. It can certainly be im-
proved by using a heated tubing system.
Fluorination of ethylene carbonate
Some of the preliminary ethylene carbonate fluorination results
were already included with the more technical article on the
minireactor design by Lang et al.[39] The conversion (C) the
yield (Y) and the selectivity (S) with respect to the formation of
monofluorinated ethylene carbonate (F1EC) are described by
Equations (1)–(6).
In all fluorination experiments, ethylene carbonate was
shown to be robust with respect to decomposition. Other than
the expected difluorinated isomers, only a very small amount
of side products, below 2 mol% with respect to the mono-
fluorinated ethylene carbonate, were observed. In Figure 5 two
19F spectra of direct fluorinations using 45 and 88% fluorine
are shown. Even with such harsh reaction conditions, good re-
sults were obtained.
n
n
n
ꢁ n
EC0
ECr
C ¼
Y ¼
S ¼
ꢂ 100
ð1Þ
ð2Þ
ð3Þ
n
EC0
ꢁ n
F1ECr
F1EC0
ꢂ 100
ꢂ 100
n
EC0
ꢁ n
F1ECr
F1EC0
n
ꢁ n
EC0
ECr
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Table 2. Results of the direct fluorination of ethylene carbonate. Entry 6: laboratory batch experiment of Kobayashi et al.;[4] entry 7: patented batch reac-
tion by Solvay Fluor;[1] entry 8: patented batch reaction by Ulsan Glas.[20]
Entry
t [h] Flow of F2
Flow of N2 T [8C] C [%] Y [%] S [%] Space-time Y[a]
Y of F2 C of F2 Y of F2EC [%]
Relative ratios
[mLminꢁ1
]
[mLminꢁ1
]
[molmꢁ3 hꢁ1
]
[%]
[%]
(trans/cis/4,4-F1EC) trans/cis/4,4-F1EC
1
2
3
4
5
6
7
8
4.0
1.8
3.3
3.1
2.0
41
–
3.0
3.0
3.0
3.0
3.0
105
–
3.6
3.6
3.6
3.6
0.1
245
–
22
22
40
22
22
50
35
55
80
45
68
69
47
–
49
32
46
39
31
70
64
76
59
70
68
58
66
–
6348
10585
8174
8173
9706
102
–
52
76
59
57
80
39
69
57
74
83
77
79
82
–
20.9 (11.4:6.7:2.8)
6.1 (3.1:2.1:0.9)
15.5 (8.6:4.8:2.1)
14.2 (7.5:4.6:1.9)
5.1 (2.5:1.9:0.7)
75 (59:11:5)[b]
–
4.0:2.4:1.0
3.5:2.4:1.0
4.0:2.3:1.0
3.8:2.4:1.0
3.5:2.6:1.0
11.8:2.2:1.0[b]
–
–
–
–
93
–
61
5.3
6533
26133
–
–
–
[a] Calculated by using the volume of the reaction containing segment (tube volume, flask volume). [b] Separate reaction, started from pure F1EC. C=con-
version, S=selectivity, Y=yield.
In Table 2, the results of our direct fluorination experiments
(entries 1–5) and those from the literature (entries 6–8) are col-
lected. Entries 1 and 2 show sets of results at different conver-
sion levels. The selectivity for F1EC was, as expected, reduced
at higher conversion and owing to the formation of doubly flu-
orinated species. The yield increased up to a maximum of
49%, which is lower than already known methods, but this
low value is also caused by the use of F1EC as a solvent. The
conversion with respect to the use of fluorine is very good,
and values of around 74 to 80% were achieved. Entries 3 and
4 compare experiments at 22 and 408C, respectively: In this
case the conversion remained constant, and a rise of the tem-
perature seemed to be advantageous. Entry 5 shows an experi-
ment using slightly diluted F2. The results of this experiment
were only slightly inferior to those obtained when using dilut-
ed fluorine. This outcome demonstrates the robustness of EC
as well as the reactor system. The results of three more classi-
cal approaches by the groups of Woo,[15] Bçse,[34] and Kobaya-
shi[35] are also included with Table 2 as entries 6–8. All three are
batch reactions, in which diluted fluorine was bubbled through
pure EC or EC diluted with F1EC.[15,34,35] Our resulting yields
with respect to fluorine use are comparable to those of Woo
and Bçse, both of which were patented as optimized process-
es. Meanwhile Kobayashi et al. employed a relatively simple
lab approach using a PFA vessel (Table 2, entry 6). Here our
method is clearly superior regarding the fluorine use. The con-
version of valuable fluorine with a fluorine use of up to 80%,
while using a significantly higher fluorine concentration at the
same time is certainly the main advantage of exploiting the
ministructured reactor. On the other hand our yield with re-
spect to the formation of F1EC is relatively low. This value is
largely influenced by use of F1EC, which was needed as sol-
vent.
of the reaction volume are taken into account. Nevertheless,
for better comparability this value was chosen.
The relative ratios of the doubly fluorinated ethylene car-
bonate isomers were constant through all of our experiments.
However, they differ strongly from the results Kobayashi
et al.[35] obtained when fluorinating pure F1EC. This difference
indicates a reduced kinetic influence, which could be caused
either by an increased temperature (unlikely) or by a faster
mixing of the biphasic gas-liquid reaction (likely).
For a better understanding of the reaction, the underlying
thermochemistry of the reaction was calculated using the relia-
ble Gaussian 3 (G3) compound method as the level of
theory.[42,43] The results of these calculations are shown in
Figure 6. There is no obvious trend of the DrG8 values going
from monofluorination (ꢁ468 kJmolꢁ1
) to perfluorination
(ꢁ508 kJmolꢁ1) of ethylene carbonates. Especially high values
were calculated for the monofluorination and when a fluorine
atom was added to a carbon center already bearing a fluorine
atom. If comparing the difluorinated isomers, the 4,4-difluoro-
ethylene carbonate (4,4-F2EC) is the energetically most pre-
ferred isomer, which contrasts with the experimental results.
This finding shows that the reaction is still kinetically con-
For an overall evaluation the space-time yield was calculat-
ed. The values of our system included with Table 2 are typical
for microreactors (e.g. compared to Jꢁhnisch et al.[31]), and
range from 6300 to 10500 molmꢁ3 hꢁ1, which is two orders of
magnitude higher than the laboratory batch approach of Ko-
bayashi et al.[35] However, this value was only calculated for the
active reaction volume. It certainly is reduced, when the walls
Figure 6. DrG8 [kJmolꢁ1] values for the direct fluorination of ethylene car-
bonate (CO3HnFm +F2!CO3Hn-1Fn+1 +HF). For the cis-F2EC and the trans-
F2EC the relative energies are compared to the global minimum 4,4-F2EC.
Calculations were carried out with the Gaussian 3 compound method.
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trolled. However, as expected for the efficient heat dissipation
in our minireactor system, our results are already closer to the
thermodynamic product than those in the batch experiment
by Kobayashi et al., that is the amount of 4,4-F2EC is much
higher in our experiments than that in reference [35] (see
Table 2).
Figure 8. The four possible monofluorinated propylene carbonate products.
CFH2 =4-fluoromethyl-1,3-dioxolan-2-one, CF=4-fluoro-4-methyl-1,3-dioxo-
lan-2-one, transCHF=4-trans-fluoro-5-methyl-1,3-dioxolan-2-one, cisCHF=4-
cis-fluoro-5-methyl-1,3-dioxolan-2-one.
For some of the direct fluorination experiments of ethylene
carbonate, the reactor temperatures were measured by using
the embedded temperature sensors. These experiments dem-
onstrated the excellent temperature control enabled by the
active cooling. No difference in temperature between the five
sensors could be detected when the cooling was active. Ex-
periments performed without active cooling and the reactor
being placed in a Styrofoam box, yielded nearly adiabatic con-
ditions and the reproducible measurement of an independent
temperature at five sensor positions. Even though the sensors
are placed only 1 mm vertically above the reaction channel,
the thermal conductivity of the reactor copper block blurred
the differences within 0.258C. Still, according to the tempera-
ture profile shown in Figure 7, the reaction mainly takes place
within the first four centimeters of the reactor. For the temper-
monofluorinated isomers (F1PC, Figure 8) and a large amount
of polyfluorinated compounds. To decrease the amount of
polyfluorinated products, only 0.44 equivalents of fluorine was
used in most experiments.
Eight experiments were investigated in a simple 23 factorial
design of experiment (DOE) approach, using temperatures of
ꢁ10 and +408C and nitrogen and fluorine flows of 2 and
4 mLminꢁ1. The results are shown in Tables 3 and 4, and the
formulas for conversion, yield, and selectivity are given in the
Equations (7)–(9). Where nPC0 is the initial PC amount and nPCr
the amount after the reaction.
n
þ n
PC0
PCr
C ¼
Y ¼
S ¼
ꢂ 100
ð7Þ
ð8Þ
ð9Þ
n
PC0
n
þ n
þ n
þ n
CH2FFPC
CHFF1PC
cisCHFF1PC
transCHFF1PC
ꢂ 100
n
PC0
n
F1PC
ꢂ 100
PCr
n
ꢁ n
PC0
Figure 7. Temperature profile of the direct fluorination of EC in acetonitrile
Unexpectedly the conversion and the yield did not show
any significant changes when the fluorine concentration was
varied between 33 and 66% and the total gas flow between 4
and 8 mLminꢁ1. This stability of the system with respect to the
fluorine concentration was unexpected. To see how far this can
be pushed, a reaction using 100% fluorine was performed
(Table 3, entry 9). In this case the lowest yield of all experi-
ments was obtained. This indicates at least a small relation be-
tween the fluorine concentration and the yield. When the reac-
tion was run with 100% fluorine and the nitrogen gas flow
switched off, some small gas bubbles were still observed in
the product stream (see the Supporting Information). This
might be a sign for some decomposition of the propylene car-
bonate. In contrast with the fluorine concentration and the
total gas flow, lowering the temperature showed a small
effect: the yield and conversion both were slightly improved.
without active cooling, liquid flow=0.67 mLminꢁ1, gas flow=6 mLminꢁ1
,
33 vol% F2, minireactor.
ature increase measured for the reactor block, liquid and air
within the box during the reaction was equal to an uptake of
105% of the energy expected for full fluorine conversion, as
calculated by using the temperature difference and the tabu-
lated heat capacities of the reactor materials (see the Support-
ing Information for details). The energy release measured is
thus within the uncertainty of the calculation and the experi-
ment, thus indicating an almost complete reaction. Therefore,
the system could be used in an optimized manner to experi-
mentally determine the reaction enthalpies of direct fluorina-
tion processes.
Fluorination of propylene carbonate
Isomer distribution
The direct fluorination of propylene carbonate (PC) allowed
the use of a broader range of temperatures because of its
much lower melting point compared with that of ethylene car-
bonate, without the need of a solvent. No approach for the
direct fluorination of PC has been published so far. Known syn-
theses are the reaction of epifluorhydrin plus CO2 or fluoropro-
pandiol plus carbonic acid dimethyl ester. Also substitution re-
actions are possible. For propylene carbonate the number of
isomers is larger than for ethylene carbonate. There are four
In all experiments, at a conversion of around 30% (Table 4),
the relative abundance of the four possible isomers did not
change. The distribution of the fluorinated isomers showed
the methyl group to be mainly fluorinated, next favored was
fluorination at the tertiary carbon atom, even though it has
just one hydrogen atom and it is sterically shielded by the
methyl group. The secondary carbon’s hydrogen atoms are the
least favored. Here the cis isomer was fluorinated slightly more
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tion of doubly fluorinated propylene carbonates. The amounts
of CF-F1PC as well as the two CHF-F1PC isomers were found to
reach around 7% concentration at most. For those isomers
a more conventional synthesis should be developed. The con-
centration for CH2F-F1PC was found to reach around 24% at
best; it seems to be the most easily accessible isomer by direct
fluorination.
Table 3. Results of an eight experiments matrix of the direct fluorination
of propylene carbonate. The N2 flow and the F2 flow were set to 2 and
4 mLminꢁ1 and the temperature to ꢁ10 and 408C. PC (3.75 g, 36.7 mmol)
and F2 (0.44 equiv) were added in each experiment. The reaction time
was 180 minutes for
4.0 mLminꢁ1
a F2 flow of 2.0 and 90 minutes for a flow
.
Entry T [8C] Flow of F2 Flow of N2 C [%] Y [%] S [%] CH2F/cisCHF/
[mLminꢁ1] [mLminꢁ1
]
transCHF/CH
[%][a]
Quantum chemical calculations using the Gaussian 3
method (Figure 10) revealed CF-F1PC to be the thermodynami-
cally preferred monofluorinated propylene carbonate isomer.
1
2
3
4
5
6
7
ꢁ10 4.0
2.0
2.0
4.0
4.0
2.0
2.0
4.0
4.0
0.0
32
26
33
26
26
30
29
29
24
23
19
26
21
20
22
22
20
17
72
72
77
80
79
73
75
68
71
32:21:19:27
31:22:20:27
32:21:19:27
31:21:20:27
31:21:21:27
32:21:19:28
32:21:19:28
31:22:20:28
32:21:19:27
40 2.0
ꢁ10 2.0
40 4.0
40 4.0
ꢁ10 2.0
ꢁ10 4.0
40 2.0
ꢁ10 4.0
8
9[b]
[a] Relative abundance, normalized by the number of hydrogen atoms at
the position of propylene carbonate and to a total sum of 100%. [b] Ex-
periment with undiluted fluorine. Not part of the eight DOE experiments.
Table 4. Influence of the temperature and the gas flows of F2 and N2 on
conversion yield and selectivity based on the experiments shown in
Table 4. Each value is the average result of the four experiments with the
same +/— parameter for each to the three variables.
Figure 10. DrG8 [kJmolꢁ1] values for the direct monofluorination of propyl-
ene carbonate (CO3H6 +F2!CO3H5F+HF). The energy difference for the
axial and equatorial propylene carbonate are also shown, as well as the rela-
tive energies of the F1PC isomers with respect to the minimum isomer CF-
F1PC. Calculations were carried out with the Gaussian 3 compound method.
[a]
+/ꢁ
T
F2 flow
N2 flow
ꢁ10/+408C
2/4 mLminꢁ1
2/4 mLminꢁ1
C [%]
C [%]
Y [%]
Y [%]
S [%]
S [%]
ꢁ
+
ꢁ
+
ꢁ
+
31
27
23
20
74
75
29
29
21
22
73
76
29
29
21
22
74
75
This thermodynamic stability of the CF-F1PC isomer can be an
explanation of why this position was preferred over fluorina-
tion at the CH2 position, even though this position is sterically
shielded by the methyl group. On the other hand, the fluorina-
tion of the kinetically most accessible methyl group was com-
puted to be thermodynamically the least favored, less stable
by 56 kJmolꢁ1 if compared with CH-F1PC. Nevertheless it was
the major product isomer found experimentally and clearly
shows that the reaction carried out in the minireactor is also
controlled by kinetics and not by thermodynamics.
[a] ꢁ=minimum value, + =maximum value.
often. Figure 9 shows the NMR distributions of the
F1PC isomers in the mixture after quenching the HF. They are
plotted against different equivalents of fluorine used in the flu-
orination reaction. The increase in F1PC concentration lowers
with increasing amount of fluorine used because of the forma-
Fluorination of closo-K2[B12H12]
After showing good fluorination stability of the cyclic carbo-
nates (EC and PC), their performance to act as highly polar sol-
vents with er =98 (EC)[44] and 64 (PC)[45] for direct fluorination
of ionic substrates was tested with the salt closo-K2[B12H12]. To
date few results on the direct fluorination of inorganic substan-
ces in mini/microreactors has been published. As a test, the
salt closo-K2[B12H12] was almost completely dissolved to
a formal concentration of 2.5 wt% in a mixture of EC/PC (4:1;
a light clouding of the liquid remained). The finely suspended
nondissolved salt went into solution within the first 30minutes
of the reaction. In Figure 11 the 19F NMR spectrum of the reac-
tion mixture after quenching the hydrogen fluoride is shown.
The yield of the perfluorinated material was determined by
NMR analysis and found to be 58%, with only 12% of polyfluo-
rinated material remaining. The main side reactions that oc-
curred were the formation of [BF4]ꢁ and BF3. Strauss and co-
Figure 9. Conversion plus yield and selectivity of the F1PC isomers (sum and
individual) plotted against equivalents fluorine used. Values after quenching
the HF. T=ꢁ208C, 240 mLhꢁ1 F2, 240 mLhꢁ1 N2, 150 mLhꢁ1 PC. C=conver-
sion, Y=yield, S=selectivity.
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to design reactors, which are precisely optimized to the condi-
tions required for direct fluorination.
In this study we also noted the high stability of polar cyclic
carbonates EC and PC against decomposition even with high
fluorine concentrations and in the presence of hydrogen fluo-
ride. This compatibility makes them an interesting solvent al-
ternative for fluorinations of ionic or other substrates in com-
parison to the volatile polar solvents currently employed for
such fluorinations (acetonitrile or methanol). In support of this
notion, our experiments on the fluorinations of toluene or
closo-[B12H12]2ꢁ with the commonly used solvent acetonitrile
tended to cause a clogging of the reactor, and which was
avoided in carbonate solvents. Moreover, the favorable fluori-
nation of closo-[B12H12]2ꢁ in the EC/PC solvent system is the
first example of an inorganic ionic substance being fluorinated
within a mini/microreactor.
Figure 11. 19F NMR spectrum of the K2[B12H12] after the reaction. Conditions:
2.5 wt% in a mixture of EC/PC (3.3:1), T=208C, liquid flow 5 mLminꢁ1, gas
flow 6.6 mLminꢁ1, 30% F2.
Finally it should to be mentioned that our minireactor has
been hitherto used for an active operation time of more than
300 hours and still shows no signs of degradation. This under-
lines the robustness of the system and how well the reactor
can withstand the corrosive conditions of direct fluorination re-
actions.
workers reported an yield of 74%[37] for the isolated product
by using a classical batch approach with acetonitrile as solvent.
In their approach, the HF formed was constantly removed by
addition of sodium fluoride and a work-up in the middle of
the reaction was necessary. The fluorination carried out using
the minireactor and our EC/PC solvent combination already
shows promise, although the yield is still lower than others re-
ported in the literature. However, our experiment was carried
out only on a 100 mg scale and was not optimized in terms of
temperature and gas/liquid flow rates. Preliminary tests indi-
cate that the use of pure PC as a solvent is also possible, but
more fluorine would be required. Thus, the cyclic carbonates
were shown to be suitable solvents for direct fluorination of
closo-K2[B12H12]. Acetonitrile has also been tested as a possible
alternative solvent that also leads to the fluorinated product,
but tended to cause undesirable clogging of the reactor. Simi-
lar to the experiments with toluene, it forms solid organic ma-
terial within the reactor.
Experimental Section
Materials and equipment
The 99.98% fluorine was donated by Solvay Fluor GmbH, Germany.
Commercially available ethylene carbonate (99%) from Alfa Aesar,
acetonitrile (HPLC grade) form VWR, and sodium fluoride (pure)
from Merck. 4-fluoro-ethylencarbonate was donated by the Solvay
Fluor, Germany. The K2[B12H12] was prepared according to the
method report by Knapp and co-workers.[46] For the NMR analysis
of the experiments an Advance II+400 NMR (Bruker, Germany)
with a 5 mm broadband fluorine observation head was used. To
enable a precise integration of the NMR signals (ethylene and pro-
pylene carbonate reactions), the spectra were recorded using the
following optimized settings: For acquisition of the19F NMR spectra
at 377 MHz were set to a spectral width of 41667 Hz, an acquisi-
tion time of 3.15 seconds and a relaxation D1 delay of 30 seconds.
The spectrum comprised 262144 data points. For acquisition of the
1H NMR spectrum at 400 MHz, a spectral width of 6410 Hz, an ac-
quisition time of 5.11 seconds, and a D1 delay of 30 seconds was
used. The spectrum comprised 65536 data points. For both nuclei,
spectra with 32 scans were recorded. An exponential function with
a value of 0.5 Hz was applied to the spectra before processing. The
phase and baseline corrections were checked for reproducibility. By
using this procedure, the error bars of the measurements were
found to be around ꢃ1%.
Conclusion
The direct fluorination of ethylene carbonate was successfully
carried out in our minireactor (channel diameter of 1 mm) and
the results were comparable to optimized large-scale batch
processes. Propylene carbonate was directly fluorinated for the
first time. The isomer distribution was investigated and CH2F-
PC was found to be the major monofluorinated isomer. The
distribution of the isomers was very stable under different re-
action conditions. Direct fluorinations without solvent and
using highly concentrated fluorine of up to 100% were shown
to be possible with only small losses in yield and conversion.
Thermodynamic calculations for ethylene and propylene car-
bonate were presented. They showed the reaction to be kineti-
cally controlled.
Fluorination procedure for toluene
First, the nitrogen flow was started to fill the gas inlet line and the
reaction channel. The liquid solution (reagent dissolved in acetoni-
trile) was loaded into a glass syringe, which was equipped with
a Luer-lock valve. The syringe was placed into the syringe pump
and the pump was started at the desired flow level, resulting in si-
multaneous flow of nitrogen and liquid solution within the reac-
tion channel. When the liquid started to exit the reactor, the fluo-
rine flow was started and turned off when the syringe had another
Toluene was found to be a difficult substrate for direct fluori-
nation in microreactors because of the formation of solids of
high molecular mass as side products.
Direct temperature measurements inside the reactors reveal
opportunities for experimental observation and determination
of thermodynamic and kinetic parameters. Those data will help
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two minutes before being empty. During the reaction, the toluene
solution tended to show a light brown color after the reaction. The
liquid flow was switched off when the syringe was empty. After
a further 20 minutes of purging the PFA vessel and the reactor, the
nitrogen flow was switched off. The product was transferred to
a different vessel, equipped with excess sodium to scrub the hy-
drogen fluoride. The mixture was then washed three times with
water to remove acetonitrile. Remaining sodium fluoride and di-
fluoride were removed by filtration. Because of the low maximal
conversion, caused by the syringe pump, yields were not deter-
mined.
Monofluorinated isomers of propylene carbonate
4-Fluoromethyl-1,3-dioxolan-2-one: 1H NMR (400 MHz, CD3CN): d=
2
3
2
4.35 (dd, 1H, JHH =8.8 Hz, JHH =6.1 Hz, H5), 4.58 (ddd, 1H, JHF
=
=
=
2
64.9 Hz, 2JHH =11 Hz, 2JHF =3.7 Hz, H6), 4.58 (ddd, 2JHF =8.8, JHF
3
8.8, 4JHF =1.4, H5), 4.71 (ddd, 1H, 2JHF =64.9, 2JHH =11.3 Hz, JHF
2.0 Hz, H6), 4.91–5.02 ppm (m, 1H, H4); 13C NMR (100.6 MHz,
CD3CN): d=65.0 (C5), 75.2 (C4) 82.2 (1JCF =155 Hz, C6), 154.9 ppm
(C2); 19F NMR (376.5 MHz, CD3CN): d=ꢁ236.4–237.6 ppm (t, 1F,
2
2JFH =46.9 Hz, 3JFH =25.3 Hz, JFH =1.4 HZ, F6)
trans-4-Fluoro-5-methyl-1,3-dioxolan-2-one:
1H NMR
CD3CN): d=1.45 (dd, 3H, JHH =6.8 Hz, JHF =0.7 Hz, H6), 4.86 (dqd,
(400 MHz,
3
4
3
3
3
1H, JHF =19.6 Hz, JHH =6.8 Hz, JHH =0.9 Hz, 5), 6.07 ppm (1H, dd,
2JHF =63.4 Hz, 3JHH =0.9 Hz, H4); 13C NMR (100.6 MHz, CD3CN): d=
15.7 (C6), 79.9 (C4), 109.2 (5), 152.4 ppm (C2); 19F NMR (376.5 MHz,
CD3CN): d=ꢁ122.4 ppm (ddq, 1F, 3JFH =19.6 Hz, 2JFH =63.4 Hz,
4JHF =0.7 Hz, F5)
Fluorination of ethylene carbonate and propylene carbon-
ate
Before fluorination, ethylene carbonate was dissolved in F1EC at
408C prior to the experiment. First the nitrogen flow was started
and the liquid was filled into the separator vessel. The circulation
pump was started with a low flow of 0.5 mLminꢁ1. When stable
gas slugs were observed at the outlet, the liquid flow was carefully
increased to the desired level of between 0.5 mLminꢁ1 and
2.5 mLminꢁ1. Once the system was running in a stable manner, the
fluorine flow was started and turned off after the desired reaction
time was complete. The liquid flow was switched off 5 minutes
after the fluorine flow was turned off. After a further 20 minutes of
purging the PFA vessel and the reactor, the nitrogen flow was
switched off. Two different work-up methods were used: For low
amounts of HF the mixture was transferred to a different vessel,
equipped with excess sodium fluoride (3 g per 3 g of substrate)
and acetonitrile (4 mL per 3 g of substrate) to scrub the hydrogen
fluoride. The mixture was stirred for two minutes, and then the so-
lution was filtered. For high amounts of HF the mixture was trans-
ferred into a PFA beaker containing an excess of silica gel and ace-
tonitrile. After stirring for 3 hours, the mixture was filtered and
washed with acetonitrile. p-Fluorotoluene was used as an internal
standard for NMR analysis (typically 0.3–0.7 g per 3 g of substrate).
1
cis-4-Fluoro-5-methyl-1,3-dioxolan-2-one: H NMR (400 MHz, CD3CN):
d=1.46 (dd, 3H, 3JHH =6.6 Hz, 4JHF =2.4 Hz, H6), 4.95 (dqd, 1H,
3JHF =25.6 Hz, 3JHH =6.6 Hz, 3JHH =4.0 Hz, H4), 6.25 ppm (dd, 1H,
2JHF =64.2 Hz, 3JHH =4.0 Hz, H5), 13C NMR (100.6 MHz, CD3CN): d=
11.3(C6), 77.8 (C4) 106.1(C5) 152.4 ppm (C2); 19F NMR (376.5 MHz,
CD3CN): d=ꢁ141.2 ppm (ddq, 1F, 3JFH =64.2 Hz, 2JFH =25.6 Hz,
4JHF =2.4 Hz, F5)
4-Fluoro-4-methyl-1,3-dioxolan-2-one: 1H NMR (400 MHz, CD3CN):
2
d=1.82 (d, 3H, 3JHF =18.0 Hz, H6), 4.46 (1H, 3JHF =32.4 Hz, JHH
=
10.6 Hz, H5), 4.60 ppm (dd, 1H, 3JHF =17.6 Hz, 2JHH =10.6 Hz, H);
13C NMR (100.6 MHz, CD3CN): d=19.9 (2JCF =34 Hz, C6), 74.9 (C5),
115.2 (C4), 152.7 ppm (C2); 19F NMR (376.5 MHz, CD3CN): d=
ꢁ92.1–ꢁ93.8 ppm (m,1F, F4)
Difluorinated isomers of propylene carbonate
1
4-Difluoromethyl-1,3-dioxolan-2-one: H NMR (400 MHz, CD3CN): d=
4.51 (dd, 1H, 2JHH =9.36 Hz, 3JHH =5.08 Hz, H5), 4.60–4.62 (m, 1H,
2
2
H5), 4.95–5.00 (m, 1H, H4), 6.05 ppm (td, 1H, JHF =26.9 Hz, JHH
=
NMR data for several mono- and difluorinated propylene
carbonates
2.6 Hz, H6); 13C NMR (100.6 MHz, CD3CN): d=64 (C5), 73 (C4), 113
(C6), 155 ppm (C2); 19F NMR (376.5 MHz, CD3CN): d=ꢁ134.0–
ꢁ136.2 ppm (m, 2F, F6)
All data are based on various 2D NMR experiments of isomer mix-
tures. The NMR data is also given for 4,4-difluoro-1,3-dioxolan-2-
one. These data have been previously published by Kobayashi[34]
and Ishii,[47] but both groups misinterpreted the signals in the H
and 19F NMR spectra. The signal formed by the CF2CH2 group is,
though it appears to be a triplet with a coupling constant of
12.0 Hz, of higher order. It is an AA’XX’ system in which a dominat-
ing 19F–19F coupling is responsible for the formation of a pseudo
triplet.
cis-4-Fluoromethyl-5-fluoro-1,3-dioxlan-2-one: 1H NMR (400 MHz,
CD3CN): d=4.77 (ddd, 1H, 2JHF =47.3 Hz, 2JHH =11.3 Hz, JHH
=
=
3
1
6.6 Hz, H5), 4.87 (ddd, 1H, 2JHF =45.3 Hz, 2JHH =11.3 Hz, JHH
3
2
3.6 Hz, H5) 5.02–5.18 (m, 1H, H4), 6.43 ppm (dd, 1H, JHF =63.8 Hz,
3JHH =4.5 Hz, H5); 13C NMR (100.6 MHz, CD3CN): d=79 (C4) 79 (C6),
105 (C5), 152 ppm (C2); 19F NMR (376.5 MHz, CD3CN): d=ꢁ140.8–
ꢁ140.6 (m, 1F, F5), ꢁ234.1 ppm (dddd, 1F, 2JHF =47.3 Hz, JHF
=
2
3
45.3 Hz, JHF =17.7 Hz, 4JFF =4.56 Hz, F6)
Structures show relevant atom numbering
trans-4-Fluoromethyl-5-fluoro-1,3-dioxlan-2-one: 1H NMR (400 MHz,
CD3CN): d=4.83 (ddd, 1H, JHF =45.4 Hz, JHH =12 Hz, JHH =2.4 Hz,
H6), 4.77 (ddd, 1H, 2JHF =47.2 Hz, 2JHH =12 Hz, 3JHF =4.6 Hz, H6),
2
2
3
3
4.92–5.07 (m, 1H, H4), 6.39 ppm (dd,1H, 2JHF =62.5 Hz, JHH
=
1.0 Hz, H5); 13C NMR (100.6 MHz, CD3CN): d=81 (C6), 81 (C4), 106
(C5), 152 ppm (C2); 19F NMR (376.5 MHz, CD3CN): d=ꢁ125.0 (ddd,
2
1F, 2JHF =62.5 Hz, 2JHF =20.1 Hz, F5), ꢁ240.2 ppm (ddd, 1F, JHF
=
4,4-F2EC
2
47.2 Hz, JHF =45.4 Hz, 3JHF =29.0 Hz, F6)
4,4-Difluoro-1,3-dioxolan-2-one: 1H NMR (400 MHz, CD3CN): d=
4.79–4.85 ppm (2H, m, 2ꢂH5); 13C NMR (100.6 MHz, CD3CN): d=71
(C5), 125 (C4), 148 ppm (C2; 19F NMR (376.5 MHz, CD3CN): d=
ꢁ74.10–ꢁ74.16 ppm (1H, m, F4+F4),
4-Fluoromethyl-4-fluoro-1,3-dioxolan-2-one:
1H NMR
(400 MHz,
CD3CN): d=4.78 (ddd, 2H, 2JHF =45 Hz, 3JHF =10 Hz, 4JHH =2.5 Hz,
H6), 4.63–4.72 ppm (m, 2H, H5), 13C NMR (100.6 MHz, CD3CN): d=
70.5 (C5), 79.5 (C6), 112.2 (C4), 151.7 ppm (C2); 19F NMR
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Fluorination of closo-K2[B12H12]
Well dried closo-K2[B12H12] (0.0907 g, 0.44 mmol) was dissolved in
EC (3.0 g) and PC (0.9 g). First the nitrogen flow of 400 mLhꢁ1 was
started and the mixture was transferred into a separator vessel.
The circulation pump was started at a low flow of 30 mLhꢁ1. When
stable gas slugs were observed at the outlet, the liquid flow was
slowly increased to 300 mLhꢁ1. The reaction gas flow was set to
a total gas flow of 400 mLhꢁ1. During the reaction, the fluorine
concentration was increased from 22% to 45%. The average fluo-
rine concentration was 33%. After 5.6 hours the fluorine was
switched of and the reactor purged with nitrogen. After quenching
the HF with calcium carbonate the standard was added and a NMR
sample prepared.
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We thank the Deutsche Forschungsgemeinschaft DFG for funding
support of this project, and Solvay Fluor GmbH for donating fluo-
rine and 4-fluoro-ethylene carbonate. This study was also sup-
ported by the Freiburg Materials Research Center FMF and the
Freiburg Institute of Advanced Studies FRIAS. We also thank
Franz Richardt in the Laboratory for Design of Microsystems Ma-
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Keywords: closo-dodecaborates · cyclic carbonates · direct
fluorination · flow reactors · microreactors
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