Investigation of (Me4N)SCF3 as a Stable, Solid and Safe Reservoir for S=CF2 as a Surrogate for Thiophosgene

Article abstract of DOI:10.1002/chem.201705240

While thiophosgene finds widespread usage on a multi-ton scale, its fluorinated counterpart S=CF₂ is essentially unexplored in synthesis. Using experimental reactivity tests, ReactIR and computational techniques, we herein showcase that the solid (Me₄N)SCF₃ functions as a safe reservoir for S=CF₂. A key feature is that the reactive electrophile is not simply released over time, but instead is liberated under activation with a protic nucleophile. The reactivity of S=CF₂ is mild, allowing large-scale and late-stage synthetic applications without special reaction control. The mechanism was fully elucidated, including a rationalization of the role of the Me₄N cation and the origins of selectivity.

Full text of DOI:10.1002/chem.201705240

DOI: 10.1002/chem.201705240
Communication
&
Reagent Alternatives
Investigation of (Me N)SCF as a Stable, Solid and Safe Reservoir
4
3
for S=CF as a Surrogate for Thiophosgene
2
[
a]
Thomas Scattolin, Maoping Pu, and Franziska Schoenebeck*
Abstract: While thiophosgene finds widespread usage on
a multi-ton scale, its fluorinated counterpart S=CF is es-
2
sentially unexplored in synthesis. Using experimental reac-
tivity tests, ReactIR and computational techniques, we
herein showcase that the solid (Me N)SCF functions as a
4
3
safe reservoir for S=CF . A key feature is that the reactive
2
electrophile is not simply released over time, but instead
is liberated under activation with a protic nucleophile. The
reactivity of S=CF is mild, allowing large-scale and late-
2
stage synthetic applications without special reaction con-
trol. The mechanism was fully elucidated, including a ra-
tionalization of the role of the Me N cation and the origins
4
of selectivity.
It has widely been recognized that the introduction of fluorine
into organic molecules allows for the modulation of various
[
1]
physical properties. While medicinal chemistry research pro-
grams widely make use of these effects, and an arsenal of syn-
thetic methods have also emerged to prepare fluorine-contain-
ing compounds, this report capitalizes on fluorine’s beneficial
impacts on reactivities for the development of safe surro-
[6]
4 3
Figure 1. Reactivity pattern of (Me N)SCF and overview.
and instead, a controlled chemical liberation in minute quanti-
ties will be required to harness its reactivity benefits.
[
2]
gates.
For example, thiophosgene (S=CCl ) finds widespread usage
We herein report a detailed investigation of the bench-
stable and easily accessible solid (Me N)SCF as a solid reservoir
2
as a coupling agent to access thioureas, isothiocyanates, thio-
4
3
[3]
carbonates as well as a range of valuable heterocycles, and
for the controlled release of S=CF . We elucidate the mecha-
2
[
4]
consequently is manufactured on a multi-ton scale. However,
thiophosgene is a volatile liquid, highly toxic and reacts vigo-
rously with nucleophiles, requiring careful reaction control. The
identification of safe alternatives is therefore of considerable
interest. Following the above mentioned impacts of fluorine
on properties, the fluorinated analogue of thiophosgene, that
nism of liberation with experimental and computational tech-
niques, precise mode of action, and also assess its beneficial
reactivity features as compared to thiophosgene.
The bench-stable salt (Me N)SCF3 was first synthesized in
4
2002 by a team at Merck KGaA and Tyrra’s group at roughly
[
7,8]
the same time.
In recent years, it has become a popular nu-
[9]
is, S=CF , bears significant potential. However, due to difficul-
cleophilic SCF source for catalytic CÀSCF bond formations,
2
3
3
[
5]
ties in the preparation and handling, it is essentially unex-
plored. It is a gas, and reported to generate a complex mixture
of compounds upon reaction with itself (Figure 1). Conse-
for example, it allows for the efficient trifluoromethylthiolation
[10]
of aryl (pseudo-)halides under transition-metal catalysis. As
[11]
part of our studies in this area, we recently untapped its po-
quently, the storage or handling of S=CF will not be feasible
tential to access chemistry, which would formally arise from S=
2
CF . We discovered that subjection of the nucleophilic “C=S”
2
source (Me N)SCF to amines gives rise to the direct and quan-
4
3
titative formation of electrophiles, that is, thiocarbamoyl fluo-
[
a] T. Scattolin, Dr. M. Pu, Prof. Dr. F. Schoenebeck
Institute of Organic Chemistry, RWTH Aachen University,
Landoltweg 1, 52074 Aachen (Germany)
E-mail: franziska.schoenebeck@rwth-aachen.de
Homepage: http://www.schoenebeck.oc.rwth-aachen.de/
[12]
rides or isothiocyanates (see Figure 1). These species serve
as key intermediates to various products, including otherwise
challenging to access trifluoromethyl amines. Other protic nu-
cleophiles, such as alcohols, also lead to the corresponding
Supporting information and the ORCID identification number(s) for the au-
thor(s) of this article can be found under https://doi.org/10.1002/
chem.201705240.
[12a,13]
thioester derivatives.
As opposed to established ap-
proaches, a non-volatile solid is used and all by-products can
Chem. Eur. J. 2017, 23, 1 – 6
1
ꢀ 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
&
&
These are not the final page numbers! ÞÞ

Communication
[
5]
readily be precipitated with low-polarity solvents, allowing the
purification of the desired products by filtration. Moreover, our
synthetic investigations with primary and secondary amines re-
vealed that there is a distinct selectivity pattern that does not
follow the general electrophile–nucleophile reactivity trend.
Formally quite nucleophilic sites, such as tertiary amines, het-
erocycles or deprotonated alcohols remained completely un-
touched, that is, the starting materials, substrate and
tion of KF. This hypothesis was subsequently also used to try
and rationalize the transformations of RÀOH with AgSCF to
3
[13]
RÀSCF .
However, our NMR spectroscopic studies of
3
(NMe )SCF suggest that it is stable and remains untouched by
4
3
itself as a solid and in solution until the amine reaction partner
is added. Moreover, our observed “NÀH” selectivity and lack of
reactivity of formally more nucleophilic sites are inconsistent
with a simple, direct release of S=CF from the salt precursor.
2
(
Me N)SCF , remained unchanged. Instead, ’heteroatomÀH’
Similarly, the observed initiation phase in the ReactIR profile
and non-exponential growth is also inconsistent with a sponta-
neous release of S=CF from (NMe )SCF Instead, the data sug-
4
3
sites are the reaction partners. However, of the available ’NÀH’
units, only the more nucleophilic and hence, less acidic, sites
2
4
3.
[
12]
transform (see Figure 1). This substrate specificity hints to-
wards an unusual mechanistic scenario.
gest a substrate-induced transformation.
To gain additional support we also tested AgSCF for its po-
3
Being encouraged by the practicability paired with late-
stage synthetic potential, we herein report our study of the
mechanism of the transformation.
tential to transform a secondary amine to a thiocarbamoyl
fluoride. This salt was previously also suggested to potentially
[13]
release S=CF2 upon AgF elimination.
However, when we
Our investigation began with an in-depth monitoring of the
mixed AgSCF with methyl 4-(methylamino)benzoate, at best
3
formation of RÀNCS from RÀNH using in situ FTIR spectrosco-
traces of thiocarbamoyl fluoride product (ꢁ2%) was observed
2
py (ReactIRꢀ). We investigated three electronically and sterical-
ly different primary amines for their propensity to form RÀNCS
with (Me N)SCF under anhydrous conditions. The data are
and starting material remained (see Scheme 2). This
4
3
shown in Scheme 1. Interestingly, for all three amines, an in-
duction period is observed under these conditions. The reac-
tion profiles are unusual and might imply that a chemical ini-
tiation event needs to take place before any conversion can
happen. As the initiation phases differ for the three amines (
ꢀ
3 vs. 6 vs. 10 min), with the least nucleophilic/electron-rich
displaying the longest, the initiation is clearly substrate-depen-
dent. Once initiated, relatively rapid and non-exponential con-
version to the RÀNCS products follows. Such non-exponential
growth is frequently associated with autocatalytic reaction be-
havior. Moreover, as seen in the 3D illustration in Scheme 1, no
intermediate was observed en route to the RÀNCS product.
A mechanistic possibility is that an S=CF electrophile is li-
2
berated. For KSCF , it has previously been suggested that the
3
salt might be unstable and might release S=CF upon elimina-
2
3
Scheme 2. a) Test whether AgSCF would also be effective. b) Proposed
Scheme 1. ReactIR reaction profiles of aniline, 1-adamantanamine and
methyl 4-aminobenzoate with (Me N)SCF under anhydrous conditions.
4 3
mechanism for the formation of isothiocyanates with (NMe
hydrous vs. protic conditions.
4 3
)SCF under an-
&
&
Chem. Eur. J. 2017, 23, 1 – 6
www.chemeurj.org
2
ꢀ 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
ÝÝ These are not the final page numbers!

Communication
observation refutes the spontaneous liberation of S=CF and
2
reinforces a special role of the tetraalkylammonium cation.
On the basis of these observations, we propose the mecha-
nism in Scheme 2. A reasonable substrate-induced initiation
would arise from an initial Me-transfer between the
[14]
(
Me N)SCF and the amine site in the substrate. This process
4 3
would only be efficient for more nucleophilic “NÀH” sites and
would now render the N-methylated substrate acidic. The
latter species could equilibrate further to the proton-ex-
+
changed counterpart (e.g. H NR ). These acidic species could
3
À
then trigger the conversion of the SCF3 anion to S=CF under
2
concomitant formation of ammonium fluoride. Once generat-
ed, the S=CF would then serve as electrophile to the ’NÀH’
2
moiety to give a thiocarbamoyl fluoride and ammonium bi-
fluoride. NEt -triggered conversion to RÀNCS would subse-
3
quently take place.
Importantly, a trace amount of methylated amine would be
fully sufficient to initiate the overall transformation. This mech-
anism would account for the fact that (i) the tetraalkylammoni-
um ion is key for reactivity, that (ii) “nucleophilic NÀH” units
are required, (iii) the occurrence of a substrate-dependent ini-
tiation phase and (iv) the non-exponential evolution of product
under anhydrous reaction conditions.
Scheme 3. Test experiment in the presence of HBF
of the reaction with observed disappearance of the initiation phase (top).
BOMD simulations (bottom) of S=CF release from (H NMe)SCF . Colour
4 2
·Et O and ReactIR profile
2
3
3
code of atoms: Cl (green), C (grey), S (yellow), F (pink), N (blue), H (white).
To gain further insight, we applied QM studies as a first ap-
proximation to evaluate the feasibility of the initiation pro-
that are not dried prior to use under open-flask reaction condi-
tions, the initiation phase equally disappeared, consistent with
small amounts of protonated amine that could function in the
SCF3 anion activation. On the contrary, a mixture of amine
(1.0 equiv), AgSCF3 (1 equiv), Et N (1.5 equiv) and HBF ·Et O
[
15]
cess. As a representative example, we studied 1-adamantan-
amine. At CPCM (DCM) B3LYP-D3/def2-tzvp level of theory, the
+
methyl transfer between NMe4 and RNH2 to generate
3
4
2
+
RNH Me was energetically slightly uphill with a reaction free
(10 mol%) gave only traces of product. These observations
would be consistent with our proposed mechanism (see
2
À1
+
+
energy (D G) of 2.5 kcalmol . From here further Me /H ex-
r
changes could in principle take place in a dynamic equilibrium
Scheme 2). With AgSCF , the required counter-cation exchange
3
+
+
À1
+
À
to generate RNH3 and RNHMe2 (D G=3.1 kcalmol ). While
to form an activated complex and later from (RNH ) (F H) to
3 2
r
+
À
these energetics will not allow quantitative Me/proton trans-
fers, they are in agreement with the prerequisite for an initia-
tion (i.e. requiring only a trace). However, as we did not involve
(RNH ) (SCF ) would not likely happen, and the crucial
3 3
À
proton for activation of SCF3 would not be propagated.
With all experimental observations accounted for in our
mechanistic model, the final open question is, how the S=CF2
electrophile is released. To assess this, we turned to computa-
À
the SCF3 counter anion and hence ion-pairing in these consid-
erations, the results must not be taken as more than a first in-
dication. We hence sought for additional experimental sup-
port.
+
À
tions. Ion pair reactivity of RÀNH3 and F CS is challenging to
3
investigate with static, gas-phase QM techniques. Thus, we
turned to DFT-based (BLYP-D3) MD, that is, Born–Oppenheimer
Mechanistically, the generation of an acidic amine appears
[16]
to be key for the liberation of S=CF . In our current mechanis-
molecular dynamics (BOMD).
The advantage is that this
2
tic picture, the observed initiation time stems from the pro-
pensity to allow for H/Me-transfers. If this mechanistic picture
is indeed true, we would expect the formation of a trace
amount of methylated amine resulting from initial Me-transfer.
Using a secondary amine, we were indeed able to detect a
methodology, in principle, maps all possible pathways at
atomic resolution from a given reactant complex under more
realistic conditions, that is, with explicit solvent.
We started our MD from a reactant complex consisting of
+
À
MeÀNH3 and F CS , embedded in 14 DCM molecules. We ran
3
trace of R NMe upon mass spectrometric analysis (see Support-
20 trajectories at BLYP-D3/6-31G level of theory at room tem-
perature for about one picosecond, of which nine progressed
to the product. We subsequently verified the results also at
2
ing Information). Moreover, given that in situ generation of an
acidic species appears to be key, the addition of an external
proton should also trigger the chain reaction, but without the
substrate-dependent initial lag time. Thus, we undertook an-
other experiment, in which we added HBF ·Et O to the reaction
[16]
B3LYP-D3/6-31G(d) level of theory.
Snapshots of the key
transformations are illustrated in Scheme 3. We observed that
S=CF2 is indeed formed. Interestingly, the release of S=CF
4
2
2
+
À
of methyl 4-aminobenzoate with (Me N)SCF . This led to a
occurs under fluoride transfer, following R NÀH···FÀCF S in-
4
3
2
2
complete disappearance of the previously observed initiation
phase and the product started to form immediately (see
Scheme 3). Similarly, using reaction conditions that are not
completely anhydrous, that is, with technical grades solvents
teraction and not through initial protonation at the formally
negative sulfur in the SCF anion. This observation is in line
3
with our calculation of the pKa of HSCF , which is predicted to
3
[17]
be only 2.7 and, as such, is acidic.
Chem. Eur. J. 2017, 23, 1 – 6
www.chemeurj.org
3
ꢀ 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
&
&
These are not the final page numbers! ÞÞ

Communication
These data present a compelling reactivity picture for the re-
Acknowledgements
lease of S=CF from (Me N)SCF in the presence of protic nu-
2
4
3
cleophiles and we next explored the practicability of employ-
ing (Me N)SCF as a surrogate for thiophosgene. We found the
We thank the RWTH Aachen and the MIWF NRW. Calculations
were performed with computing resources granted by JARA-
HPC from RWTH Aachen University under project ‘jara0091’.
We are grateful to Andre Jung (RWTH Aachen) for the DSC
measurement.
4
3
transformation of (Me N)SCF with amines to be very efficient
4
3
in a range of solvents, that is, DCM, toluene, EtOAc, acetone,
[
12b]
THF, MeCN, MTBE, CPME.
All side-products that are formed
in the reaction are solids, allowing their precipitation with low
polarity solvents. An open question is the heat generated by
Conflict of interest
the reaction of S=CF (and its release) as compared to thio-
2
phosgene. We performed a direct reactivity comparison of the
coupling of thiophosgene versus (Me N)SCF with methyl 4-
The authors declare no conflict of interest.
4
3
aminobenzoate at 10 mmol scale (ca. 1.5 g). Both reagents
were added in one portion to the respective solutions of
amine and triethylamine in DCM. While this resulted in vigo-
rous and uncontrolled reactivity for thiophosgene (see
Figure 2) that rapidly released so much heat that DCM started
boiling (>158C temperature increase in a few seconds), the re-
action with (Me N)SCF showed only a slow warming of 58C
Keywords: computational chemistry · fluorine · late-stage
functionalization · reaction mechanisms · thiophosgene
[1] a) K. Mꢁller, C. Faeh, F. Diederich, Science 2007, 317, 1881; b) S. Purser,
P. R. Moore, S. Swallow, V. Gouverneur, Chem. Soc. Rev. 2008, 37, 320;
c) O. A. Tomashenko, V. V. Grushin, Chem. Rev. 2011, 111, 4475; d) T.
Liang, C. N. Neumann, T. Ritter, Angew. Chem. Int. Ed. 2013, 52, 8214;
Angew. Chem. 2013, 125, 8372; e) P. A. Champagne, J. Desroches, J.-D.
Hamel, M. Vandamme, J.-F. Paquin, Chem. Rev. 2015, 115, 9073; f) A. Tlili,
F. Toulgoat, T. Billard, Angew. Chem. Int. Ed. 2016, 55, 11726; Angew.
Chem. 2016, 128, 11900.
4
3
over a period of 20 minutes.
[
2] Fluorine’s impact on conformation or inductive/electrostatic effects will
ultimately influence also reactivity. See: a) C. Sparr, W. B. Schweizer,
H. M. Senn, R. Gilmour, Angew. Chem. Int. Ed. 2009, 48, 3065; Angew.
Chem. 2009, 121, 3111; b) L. E. Zimmer, C. Sparr, R. Gilmour, Angew.
Chem. Int. Ed. 2011, 50, 11860; Angew. Chem. 2011, 123, 12062; c) M. C.
Nielsen, K. J. Bonney, F. Schoenebeck, Angew. Chem. Int. Ed. 2014, 53,
5903; Angew. Chem. 2014, 126, 6013.
[
[
[
3] S. Sharma, Synthesis 1978, 1978, 803.
4] J. I. Grayson, Org. Process Res. Dev. 1997, 1, 240.
5] a) S. J. Tavener, D. J. Adams, J. H. Clark, J. Fluorine Chem. 1999, 95, 171;
b) W. Dmowski, A. Haas, J. Chem. Soc. Perkin Trans. 1 1987, 1, 2119; c) A.
Haas, W. Klug, Chem. Ber. 1968, 101, 2609; d) J. F. Harris, J. Org. Chem.
Figure 2. Assessment of heat generation in the reactions of thiophosgene
(left) versus (Me
4
N)SCF
3
(right) to give the corresponding RÀNCS (i.e. methyl
4-isothiocyanatobenzoate).
1
967, 32, 2063.
[
[
6] For the “unreactive sites”, the starting materials remain unchanged.
7] a) P. Kirsch, G-V. Roeschenthaler, G. Bissky, A. Kolomeitsev (Merck KGaA),
DE10254597, 2002; b) D. Naumann, B. Hogea, Y. L. Yagupolskii, W. E.
Tyrra, J. Fluorine Chem. 2003, 119, 101.
Moreover, a differential scanning calorimetry analysis (DSC)
of the (Me N)SCF salt from 108C to 1608C showed that no
4
3
exotherm is observed, indicating that the salt is safe to use up
to 1608C (see Supporting Information for additional informa-
tion).
[8] We made use of a slightly modified procedure to synthesize the
Me N)SCF reagent, which is reported in reference 11c.
(
4
3
[
9] F. Toulgoat, T. Billard in Modern Synthesis Processes and Reactivity of Flu-
orinated Compounds: Progress in Fluorine Science (Eds.: H. Groult, F.
Leroux, A. Tressaud), Elsevier Science UK, 2017, pp. 141.
In summary, a mechanistic study of the mode of action and
selectivity of the solid reagent, (Me N)SCF , as a safe surrogate
[10] a) C.-P. Zhang, D. A. Vicic, J. Am. Chem. Soc. 2012, 134, 183; b) C.-P.
Zhang, D. A. Vicic, Chem. Asian J. 2012, 7, 1756.
4
3
for thiophosgene was conducted. Our studies suggest that an
[
11] a) A. B. Dꢁrr, G. Yin, I. Kalvet, F. Napoly, F. Schoenebeck, Chem. Sci. 2016,
, 1076; b) G. Yin, I. Kalvet, U. Englert, F. Schoenebeck, J. Am. Chem. Soc.
015, 137, 4164; c) G. Yin, I. Kalvet, F. Schoenebeck, Angew. Chem. Int.
S=CF electrophile is generated in a controlled fashion upon
2
7
2
activation with a protic nucleophile. Under anhydrous condi-
tions, the process is likely initiated by a substrate-dependent
Ed. 2015, 54, 6809; Angew. Chem. 2015, 127, 6913.
[
12] a) T. Scattolin, K. Deckers, F. Schoenebeck, Angew. Chem. Int. Ed. 2017,
series of Me- and proton transfers from the NMe cation, con-
4
5
6, 221; Angew. Chem. 2017, 129, 227; b) T. Scattolin, A. Klein, F. Schoe-
sistent with its crucial role in the transformation (AgSCF gives
3
nebeck, Org. Lett. 2017, 19, 1831; c) T. Scattolin, K. Deckers, F. Schoene-
beck, Org. Lett. 2017, 19, 5740.
no reaction). This substrate-dependent initiation phase will dis-
appear in the presence of exogenous HBF ·Et O (10 mol%) or
[13] a) J.-B. Liu, X.-H. Xu, Z.-H. Chen, F.-L. Qing, Angew. Chem. Int. Ed. 2015,
4, 897; Angew. Chem. 2015, 127, 911; b) Q. Glenadel, A. Tlili, T. Billard,
4
2
5
non-anhydrous conditions. In contrast to previous literature
Eur. J. Org. Chem. 2016, 1955.
statements, (Me N)SCF3 is stable as a solid and in solution
4
[
14] a) B. P. Callahan, R. Wolfenden, J. Am. Chem. Soc. 2003, 125, 310; b) H.
Gunaydin, O. Acevedo, W. L. Jorgensen, K. N. Houk, J. Chem. Theory
Comput. 2007, 3, 1028; c) According to our calculations the solvation
free energy barriers in MeCN or DCM only deviate by, respectively 0.1
under anhydrous conditions, liberating the S=CF not by itself
2
in an equilibrium, but under chemical activation and direct
+
À
fluoride transfer, following R NÀH···FÀCF S interaction. A sys-
3
2
À1
and 0.4 kcalmol from those in water.
tematic comparison with S=CCl revealed much less exother-
2
[
15] Gaussian 09, Revision D.01, M. J. Frisch, G. W. Trucks, H. B. Schlegel, G. E.
Scuseria, M. A. Robb, J. R. Cheeseman, G. Scalmani, V. Barone, B. Men-
nucci, G. A. Petersson, H. Nakatsuji, M. Caricato, X. Li, H. P. Hratchian,
mic reactivity of the fluorinated analogue, requiring no reac-
tion control even at larger scale.
&
&
Chem. Eur. J. 2017, 23, 1 – 6
www.chemeurj.org
4
ꢀ 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
ÝÝ These are not the final page numbers!

Communication
A. F. Izmaylov, J. Bloino, G. Zheng, J. L. Sonnenberg, M. Hada, M. Ehara,
K. Toyota, R. Fukuda, J. Hasegawa, M. Ishida, T. Nakajima, Y. Honda, O.
Kitao, H. Nakai, T. Vreven, J. A. Montgomery, Jr., J. E. Peralta, F. Ogliaro,
M. Bearpark, J. J. Heyd, E. Brothers, K. N. Kudin, V. N. Staroverov, R. Ko-
bayashi, J. Normand, K. Raghavachari, A. Rendell, J. C. Burant, S. S. Iyen-
gar, J. Tomasi, M. Cossi, N. Rega, J. M. Millam, M. Klene, J. E. Knox, J. B.
Cross, V. Bakken, C. Adamo, J. Jaramillo, R. Gomperts, R. E. Stratmann,
O. Yazyev, A. J. Austin, R. Cammi, C. Pomelli, J. W. Ochterski, R. L. Martin,
K. Morokuma, V. G. Zakrzewski, G. A. Voth, P. Salvador, J. J. Dannenberg,
S. Dapprich, A. D. Daniels, ꢂ. Farkas, J. B. Foresman, J. V. Ortiz, J. Cio-
slowski, D. J. Fox, Gaussian, Inc. Wallingford CT, 2009.. See Supporting
Information for further details.
2015, 21, 5477; b) K. Black, P. Liu, L. Xu, C. Doubleday, K. N. Houk, Proc.
Natl. Acad. Sci. USA 2012, 109, 12860; c) L. Wang, A. Titov, R. McGibbon,
F. Liu, V. S. Pande, T. J. Martꢃnez, Nat. Chem. 2014, 6, 1044; d) M. Pu, T.
Privalov, Chem. Eur. J. 2015, 21, 17708.
3 3
[17] HSCF & SCF were optimized at B3LYP/6-31G(d). SMD (Water), energies
were calculated at B3LYP/tzvp. The pKa value was calculated with COS-
MOthermX (F.Eckert, A. Klamt, COSMOtherm, Version C30 1601, Release
12.15; COSMOlogic GmbH &Co. KG, Germany, 2010).
Manuscript received: November 4, 2017
Accepted manuscript online: December 4, 2017
Version of record online: && &&, 0000
[
16] For recent use of MD to study reactivity and adequateness of applied
level of theory, see: a) C. Loerbroks, E. Boulanger, W. Thiel, Chem. Eur. J.
Chem. Eur. J. 2017, 23, 1 – 6
www.chemeurj.org
5
ꢀ 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
&
&
These are not the final page numbers! ÞÞ

Communication
COMMUNICATION
Experiments and computations show-
&
Reagent Alternatives
case the solid (Me N)SCF functioning
4
3
T. Scattolin, M. Pu, F. Schoenebeck*
& – &&
Investigation of (Me N)SCF as a
as a safe reservoir for S=CF and shed
2
light on the mechanism of activation.
&
4
3
Stable, Solid and Safe Reservoir for S=
CF as a Surrogate for Thiophosgene
2
&
&
Chem. Eur. J. 2017, 23, 1 – 6
www.chemeurj.org
6
ꢀ 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
ÝÝ These are not the final page numbers!