A Very Strong Methylation Agent: [Me2Cl][Al(OTeF5)4]

Article abstract of DOI:10.1002/anie.201904007

A new chloronium-containing salt, [Me₂Cl][Al(OTeF₅)₄], was synthesized on multigram scale by means of a simple one-pot procedure. The isolated product can be handled at room temperature and used as a strong electrophilic methylation agent. This is demonstrated by the methylation of the very weak bases P(CF₃)₃, PF₃, MeI, and MeBr.

Full text of DOI:10.1002/anie.201904007

A Journal of the Gesellschaft Deutscher Chemiker
Angewandte
Chemie
International Edition
www.angewandte.org
Accepted Article
Title: A Very Strong Methylation Agent: [Me2Cl][Al(OTeF5)4]
Authors: Sebastian Hasenstab-Riedel, Sebastian Hämmerling, Simon
Steinhauer, Helmut Beckers, and Günther Thiele
This manuscript has been accepted after peer review and appears as an
Accepted Article online prior to editing, proofing, and formal publication
of the final Version of Record (VoR). This work is currently citable by
using the Digital Object Identifier (DOI) given below. The VoR will be
published online in Early View as soon as possible and may be different
to this Accepted Article as a result of editing. Readers should obtain
the VoR from the journal website shown below when it is published
to ensure accuracy of information. The authors are responsible for the
content of this Accepted Article.
To be cited as: Angew. Chem. Int. Ed. 10.1002/anie.201904007
Angew. Chem. 10.1002/ange.201904007
Link to VoR: http://dx.doi.org/10.1002/anie.201904007
http://dx.doi.org/10.1002/ange.201904007

10.1002/anie.201904007
Angewandte Chemie International Edition
COMMUNICATION
A Very Strong Methylation Agent: [Me2Cl][Al(OTeF5)4]
Sebastian Hämmerling, Günther Thiele, Simon Steinhauer, Helmut Beckers, Carsten Müller,
Sebastian Riedel*
Dedicated to Prof. Dr. Hans-Ulrich Reißig on the occasion of his 70th birthday
Abstract: A new chloronium containing salt [Me2Cl][Al(OTeF5)4] is
synthesized on a multigram-scale by means of a simple one-pot
procedure. The isolated product can be handled at room temperature
and used as a strong electrophilic methylation agent. This is
demonstrated by the methylation of the very weak bases P(CF3)3, PF3,
MeI and MeBr.
chloromethane at –40 °C, the initial reaction mixture changes
color, starting from a yellow tinge to a colorless solution within five
minutes. Distillation of excess MeCl from the reaction mixture
under reduced pressure leads to the formation of a colorless
precipitate which still contains solvate MeCl, which can be
removed in vacuo at room temperature. Once solvent free,
[Me2Cl][Al(OTeF5)4] (1) is isolated as a colorless powder and
stable for hours at room temperature, where it turns brown within
days, however, IR and NMR indicate the absence of impurities or
decomposition. The NMR spectra of 1 yields the signal for the
methyl groups with the expected chemical shifts and coupling
constants ((1H) = 5.61 ppm; (13C) = 52.7 ppm; 1J(13C,1H) =
162.1 Hz, 1H NMR spectrum see Figure S1) and a cross signal in
the 1H,13C-HMBC due to the 3J(13C,1H) coupling. Its IR data
corresponds well to literature reported values.[7,8,12]
Strong and easily-accessible electrophilic methylation agents are
rare. The strongest known methylation systems are MeF/SbF5 in
liquid SO2,[1,2] or anhydrous HF,[3] and the closo-carborates
Me(CHB11Me5X6) (X = Cl, Br).[4] It is possible to crystallize
methylated SO2, i.e., [MeSO2][SbF6], from
a mixture of
[1,2]
MeF/SbF5/SO2.
However, due to secondary reactions of the
strong Lewis acid SbF5 as oxidizer, its synthetic usability is
limited.[5] The application of methyl cations stabilized by closo-
carborates is limited due to the small-scale accessibility of these
compounds.[6] Another class of strong alkylation agents are salts
with dialkylhalonium cations.[7,8] Such cations can be prepared by
the reaction of SbF5·MeF with MeX (X= I, Br, Cl) in liquid SO2.
Their alkylation strength increases from the iodonium [Me2I]+ to
the chloronium cation [Me2Cl]+. The elusive fluoronium cation
[Me2F]+ – proposed to be an even stronger methylation agent – is
experimentally still unknown. Attempts to detect this elusive
species failed so far and yield instead decomposition products
Colorless crystals suitable for X-Ray diffraction where grown from
a MeCl/n-pentane mixture at –80 °C. 1·MeCl crystallizes in the
monoclinic space group P21/n (Figure 1). Both, solvate MeCl and
the aluminate anion are disordered as shown in the supporting
information (Figure S2). The cation [Me2Cl]+ has a C1–Cl1–C2
bond angle of 101.0(7) ° with a considerably elongated C–Cl bond
+
such as HF and C2F5 cations.[9] In contrast, a bis-silylated
fluoronium salt, [(Me3Si)2F][B(C6F5)4],[10] and a cage like C-F-C
hydrocarbon based system were described recently.[11]
(d(C1–Cl1) = 183.9(16) pm,
d(C2–Cl1) = 180.1(19)
pm)
Another access to the [Me2Cl]+ cation was reported by using a
Brønsted superacid. Addition of chloromethane to H(CHB11Cl11)
was reported to yield first HCl and Me(CHB11Cl11). The latter
reacts further with a second chloromethane molecule to the
[Me2Cl]+ cation.[12] We recently reported the synthesis of a new
Brønsted superacid, [ArH][Al(OTeF5)4] (Ar=ortho-C6H4F2).[13] It is
obtained in multi-gram batches by a simple one-step synthesis
based on the reaction of triethylaluminium (AlEt3) and pentafluoro-
orthotelluric acid (HOTeF5) in ortho-difluorobenzene (oDFB). We
were thus interested in the generation of strong methylation
agents, starting from this readily-available Brønsted superacid.
Here, we present the simple one-step synthesis of the
dimethylchloronium salt [Me2Cl][Al(OTeF5)4]·MeCl (1·MeCl) using
the superacidic system of in-situ generated H[Al(OTeF5)4] in neat
chloromethane (equation 1). Upon addition of pentafluoro-
compared to free MeCl (d(C–Cl) = 178.1 pm).[14] The structure of
the cation is similar to those in [Me2Cl][CHB11Cl11].[12] The cation
shows a weak contact to the embedded MeCl through a weak C2–
H–Cl2 hydrogen bridge[15] (d(C2–Cl2) = 339.2(18) pm) and three
further contacts to neighboring anions by weak C–H–F hydrogen
bridges (d(C1–F) = 316.7(21) pm, d(C2–F) = 313.2(22) pm and
d(C2–F) = 311.2(22) pm, see Figure S3).
orthotelluric acid to
a
solution of triethylaluminium in
[*]
M. Sc. S. Hämmerling, Dr. G. Thiele, Dr. S. Steinhauer, Dr. H.
Beckers, Dr. C. Müller, Prof. Dr. S. Riedel
Freie Universität Berlin, Institut für Chemie und Biochemie
Fabeckstr.34/36, 14195 Berlin (Germany)
E-mail: s.riedel@fu-berlin.de
Supporting information for this article is given via a link at the end of
the document.
Figure 1. Molecular structure of 1·MeCl in the solid state. H-Atoms of solvate
MeCl are omitted for clarity. Thermal ellipsoids drawn at 50% probability level.
This article is protected by copyright. All rights reserved.

10.1002/anie.201904007
Angewandte Chemie International Edition
COMMUNICATION
Selected bond length (pm) and angles (°): C1-Cl1 183.9(16), C2-Cl1 180.1(19),
C1-Cl1-C2 101.0(7), Al-O1 184.5(14), Al-O2 166.4(14), Al-O3 178.7(14), Al-O4
176.1(14), O1-Te1 180.7(11), O1-Al-O2 112.0(7), O1-Al-O3 107.0(7), O1-Al-O4
110.8(7), O2-Al-O3 114.6(8), O3-Al-O4 105.0(7), O4-Al-O2 107.4(7).
1 is soluble in MeCl, SO2 and SO2ClF, but decomposes in solution
within days at room temperature, yielding MeOTeF5 from the
methylation of the weakly coordinating anion. It can thus be used
as Me+ transfer reagent.
To evaluate this methylation ability, fluorinated phosphorus(III)
compounds P(CF3)3 and PF3 were chosen as reagent due to their
weak nucleophilicity and basicity.[3,16] The reaction of 1 and
P(CF3)3 (equation 2) slowly takes place at room temperature with
formation of the previously reported cation [MeP(CF3)3]+, as
monitored by its characteristic 31P NMR spectrum ((31P) =
40.6 ppm, decet of quartets with 2J(31P,19F) = 127.6 Hz, 2J(31P,1H)
= 15.7 Hz, see Fig. 2).[3] The formation of [MeP(CF3)3]+ indicates
that the methylation strength of 1 is similar to that of the strongest
known methylation system MeF/HF/SbF5. Furthermore, reaction
2
occurres at room temperature while the reaction of
MeF/HF/SbF5 and P(CF3)3 requires temperatures below –10 °C to
prevent secondary reactions of the phosphonium cation in
solution.
Figure 2. 31P NMR spectra (161.2 MHz, SO2, 20 °C) of [MeP(CF3)3][Al(OTeF5)4]
(top) and [MePF3][Al(OTeF5]4] (2, bottom). Experimental spectra are shown in
black, simulated ones are depicted in gray.
The [MePF3][Al(OTeF5)4] salt decomposes in SO2 solution at
room temperature much faster than 1, forming initially the
[MePF2(OTeF5)]+ cation which further reacts to [MePF(OTeF5)2]+,
as observed by NMR spectroscopy. Depending on the number of
fluorine substituents in [MePF3–x(OTeF5)x]+, (31P) shifts from
53.1 ppm (x = 0), to 45.2 ppm (x = 1) and 37.1 ppm (x = 2). Within
this series the 1J(31P,19F) coupling constants decrease from
1277 Hz to 1233 Hz and 1192 Hz, respectively. This
decomposition pathway of the aluminate anion indicates the
strong Lewis acidic character of the phosphonium cations. We
note that the fluoride ion affinity (FIA) of the phosphonium cations
[MePF3–x(OTeF5)x]+ decrease with increasing the number x of the
OTeF5 substituents (Table 1). This observation is surprising as it
not only indicates an increase in stability by substitution of F by
the OTeF5 group, it also contradicts common consensus, that the
OTeF5 substituent has a higher group electronegativity than
fluorine.[18] Indeed, the fluoride ion affinity of e.g. E(OTeF5)5 was
proved to be higher than that of EF5 (E = As, Sb)[19], and this
conclusion is in accordance with our result of the increase of the
FIA values within the series PF5–x(OTeF5)x with x = 0 - 5 (see Fig.
S4). These seemingly contradictory results for the two series of
the phosphonium cations and the neutral hypervalent species can
be attributed to the bonding properties of the OTeF5 group. Our
preliminary NBO analysis[20] revealed that substitution of F by the
OTeF5 group in [MePF3–x(OTeF5)x]+ indeed reduces the NPA
charge at the central phosphorus atom and thus, decreases its
Lewis-acidity (Fig. S5). This trend is generally found for the series
[MeEF3–x(OTeF5)x]+ (E = P, As, Sb), [PF4–x(OTeF5)x]+ and also for
the neutral species PF5–x(OTeF5)x (see Fig. S5), which can most
probably be attributed to both, a higher ionic character of the P–F
bond (Table S3) and a stronger -bonding of the oxygen lone
pairs especially in the 2-center-2-electron bonds of these systems.
On the other side, the F5TeO group preferentially stabilizes 3-
center-4-electron bonds in hypervalent species compared to a
An even more challenging cation is [MePF3]+ which was, so far,
only detected in the gas phase by ICR mass spectroscopy.[17]
Treatment of PF3 with 1 in liquid SO2 at –10 °C leads to the
formation of the elusive [MePF3]+ cation in the salt
[MePF3][Al(OTeF5)4] (2) (equation 3). This is supported by the
observed doublet of quartets in the 1H NMR spectrum at (1H) =
3.35 ppm with 2J(31P,1H) = 18.1 Hz, and 3J(19F, 1H) = 8.1 Hz. The
signal in the 31P NMR at (31P) = 53.1 ppm revealed a smaller
1J(31P,19F) coupling constant of 1277 Hz compared to the signal
obtained for PF3 in SO2 solution with 1403 Hz. The reaction
product was isolated as an off-white powder, but rapidly
decomposes at room temperature to a dark brown oil. A 10 mol%
excess of 1 within the reaction mixture allows quick handling of 2
at room temperature. The experimental IR spectra of 2, shown in
Table S1, is in good agreement with the calculated spectra at the
RI-B3LYP-D3/def2-TZVPP level of theory.
This article is protected by copyright. All rights reserved.

10.1002/anie.201904007
Angewandte Chemie International Edition
COMMUNICATION
fluorine ligand, because it allows for a more efficient charge
delocalization via the *(P–O) orbitals than the *(P–F) orbitals
(Fig. S6). This, most likely result in the higher FIA values for the
OTeF5 substituted neutral derivatives.
1H,13C-HMBC).[7,8] [Me2I][Al(OTeF5)4] was obtained as colorless
powder, stable at room temperature and soluble in
dichloromethane without decomposition for months, while
[Me2Br]+ is only as stable as 1.
Based on the very high computed FIA value of [MePF3]+ (851
kJ·mol–1), this is an even stronger Lewis acid than the previously
reported exceptional strong Lewis acid [FP(C6F5)3]+ with a FIA
value of 773 kJ·mol–1.[21] The experimental determination of the
Lewis acidity of the [MePF3]+ cation by either 31P NMR
spectroscopy using triethylphosphine oxid (Gutmann-Beckett
method),[22] or IR spectroscopy using an acetonitrile adduct[23] are
not suitable due to the methylation reactions of the substrates.[24]
Therefore, a solution of 2 was combined with a solution of either
[nBu4N][PF6] (equation 4) or [nBu4N][SbF6] at –70 °C and allowed
to warm to room temperature.
According to the proton affinities (PA) SO2 should be methylated
by 1. However this is not observed as 1 is handled in liquid SO2
at room temperature. Therefore the methyl cation affinities (MCA)
are investigated (see Table 2, more values see Table S2). The
MCA predicts the reactivity of 1 in liquid SO2 – i.e. the not
observed methylation of SO2 with 1 – correctly. Furthermore, even
more methylation reaction that are predicted wrongly with the PA,
are predicted correctly with the MCA like the methylation of
acetonitrile with [Me3O]+.[26] Hence literature values of PA may be
a first reactivity hint for methylation reactions, but calculating the
MCA is quit convenient and suggested.
The reaction of 2 with [PF6]– anions yields MePF4[25] as observed
in the 31P NMR spectrum (quintet of quartets, (31P) = –27.0 ppm,
1J(31P,19F) = 967.9 Hz, 2J(31P,1H) = 7.2 Hz). In contrast, the
[SbF6]– anion is stable in the presence of 2, and it can be
concluded that the Lewis acidity of 2 in solution is stronger than
that of PF5, but weaker than SbF5. The reaction of the chloronium
salt 1 with [nBu4N][PF6] or [nBu4N][SbF6] at room temperature in
SO2 yields MeF and PF5 or SbF5, respectively (equation 5). This
observation exemplifies the high electrophilicity of 1.
[nBu4N][AsF6] reacts with 1 under formation of MeF. The formation
of AsF5 could not be verified as the reaction mixture rapidly forms
an insoluble gel – even at –40 °C.
Table 2. Experimental and calculated[a] proton affinities (PA) and methyl
cation affinities (MCA)[b] in kJ·mol–1
Compound
PA
MCA
SO2
672.3 [27]
229.1, 254[28]
279.2, 260[28]
294.4, 265[28]
323.7
MeCl
MeBr
MeI
647.3 [27]
664.2 [27]
691.7 [27]
P(CF3)3
PF3
690.9
367.2
695.3 [27], 669±21 [17]
792.0 [27]
370.2
Me2O
MeCN
374.0
779.6 [27]
414.2
Table 1. Fluoride ion affinities (FIA) of selected Lewis acids in kJ·mol–1
.
[a] values in italics at RI-B3LYP-D3/def2-TZVPP level
[b] MCA = –ΔH0 for reaction B + Me+  BMe+
Compound
BF3
FIA[a]
356
385
445
500
773
Compound
FIA[a]
767
782
811
811
851
[MeP(OTeF5)3]+
[MePF(OTeF5)2]+
[MePF2(OTeF5)]+
[MeP(CF3)3]+
[MePF3]+
In conclusion, we report
a simple one-pot synthesis of
[Me2Cl][Al(OTeF5)4] (1), which is available on a multi-gram scale
and can be handled at room temperature and stored for several
weeks at –40 °C. The usage of 1 as a strong methylation agent
was demonstrated by methylation of very weak bases yielding the
[MeP(CF3)3]+, [Me2Br]+ and [Me2I]+ cations, as well as the first
spectroscopic proof of the elusive [MePF3]+ cation. The
PF5
AsF5
SbF5
[FP(C6F5)3]+
methylating agent
1
combines the advantages of
[a] RI-B3LYP-D3/def2-TZVPP level using TMS+/TMSF as anchor point.[19]
Me(CB11Me5X6)[4] and the MeF/SbF5[1,2] system: a Lewis acid free,
non-oxidizing compound with a large-scale accessibility.
Iodomethane, and the even less basic molecule bromomethane,
are also methylated quantitatively by 1 under formation of [Me2I]+
or [Me2Br]+ respectively (equation 6), as proven by IR and NMR
spectroscopy ([Me2I]+: (1H) = 3.59 ppm; (13C) = 11.7 ppm;
1J(13C,1H) = 158.7 Hz; 1H,13C-HMBC: cross signal; [Me2Br+:
(1H) = 5.31 ppm; (13C) = 40.2 ppm; 1J(13C,1H) = 161.4 Hz;
Acknowledgements
The authors gratefully acknowledge the research training network
“Fluorine as a key element” for financial support, Solvay Fluor
GmbH for donating chemicals and the Zentraleinrichtung für
This article is protected by copyright. All rights reserved.

10.1002/anie.201904007
Angewandte Chemie International Edition
COMMUNICATION
Datenverarbeitung (ZEDAT) of the Freie Universität Berlin for
computational resources and support. The project was supported
by the Deutsche Forschungsgemeinschaft (DFG, German
Research Foundation) – project id 387284271 – CRC 1349:
Fluorine-Specific Interactions. GT was supported by a Liebig
Scholarship of the Fond der Chemischen Industrie.
Keywords: methylation • weakly coordinating anion •
pentafluoro-orthotellurates • fluorine chemistry • Lewis acids
[1]
[2]
[3]
[4]
[5]
[6]
R. J. Gillespie, F. G. Riddell, D. R. Slim, J. Am. Chem. Soc. 1976, 98,
8069.
R. Minkwitz, D. Bernstein, H. Preut, W. Sawodny, H. Härtner, Z. Anorg.
Allg. Chem. 1991, 606, 157.
O. Shyshkov, U. Dieckbreder, T. Drews, A. Kolomeitsev, G.-V.
Röschenthaler, K. Seppelt, Inorg. Chem. 2009, 48, 6083.
T. Kato, E. Stoyanov, J. Geier, H. Grützmacher, C. A. Reed, J. Am. Chem.
Soc. 2004, 126, 12451.
M. J. Molski, D. Mollenhauer, S. Gohr, B. Paulus, M. A. Khanfar, H.
Shorafa, S. H. Strauss, K. Seppelt, Chem. Eur. J. 2012, 18, 6644.
a) V. Geis, K. Guttsche, C. Knapp, H. Scherer, R. Uzun, Dalton Trans.
2009, 2687; b) I. M. Riddlestone, A. Kraft, J. Schaefer, I. Krossing,
Angew. Chem. 2018, 130, 14178; Angew. Chem. Int. Ed., 2018, 57,
13982.
[7]
[8]
[9]
G. A. Olah, J. R. DeMember, J. Am. Chem. Soc. 1970, 92, 718.
G. A. Olah, J. R. DeMember, J. Am. Chem. Soc. 1969, 91, 2113.
E. S. Stoyanov, J. Phys. Chem. A 2017, 121, 2918.
[10] M. Lehmann, A. Schulz, A. Villinger, Angew. Chem. 2009, 121, 7580;
Angew. Chem. Int. Ed., 2009, 48, 7444.
[11] a) C. R. Pitts, M. G. Holl, T. Lectka, Angew. Chem. 2018, 130, 1942;
Angew. Chem. Int. Ed., 2018, 57, 1924; b) M. D. Struble, M. T. Scerba,
M. Siegler, T. Lectka, Science 2013, 340, 57.
[12] E. S. Stoyanov, I. V. Stoyanova, F. S. Tham, C. A. Reed, J. Am. Chem.
Soc. 2010, 132, 4062.
[13] A. Wiesner, T. W. Gries, S. Steinhauer, H. Beckers, S. Riedel, Angew.
Chem. 2017, 129, 8375; Angew. Chem. Int. Ed., 2017, 56, 8263.
[14] S. L. Miller, L. C. Aamodt, G. Dousmanis, C. H. Townes, J. Kraitchman,
J. Chem. Phys. 1952, 20, 1112.
[15] a) A. Bondi, J. Phys. Chem. 1964, 68, 441; b) J. Emsley, Chem. Soc.
Rev. 1980, 9, 91.
[16] J. Apel, J. Grobe, Z. Anorg. Allg. Chem. 1979, 453, 28.
[17] R. R. Corderman, J. L. Beauchamp, Inorg. Chem. 1978, 17, 1585.
[18] D. Lentz, K. Seppelt, Angew. Chem. 1978, 90, 390; Angew. Chem. Int.
Ed. 1978, 17, 355.
[19] H. Böhrer, N. Trapp, D. Himmel, M. Schleep, I. Krossing, Dalton Trans.
2015, 44, 7489.
[20] Alan E. Reed, Robert B. Weinstock, Frank Weinhold, J. Chem. Phys.
1985, 83, 735.
[21] a) C. B. Caputo, L. J. Hounjet, R. Dobrovetsky, D. W. Stephan, Science
2013, 341, 1374; b) L. Greb, Chem. Eur. J. 2018, 24, 17881.
[22] a) U. Mayer, V. Gutmann, W. Gerger, Monatshefte für Chemie 1975, 106,
1235; b) M. A. Beckett, G. C. Strickland, J. R. Holland, K. Sukumar
Varma, Polymer 1996, 37, 4629.
[23] a) I. R. Beattie, T. Gilson, J. Chem. Soc. 1964, 2292; b) K. F. Purcell, R.
S. Drago, J. Am. Chem. Soc. 1966, 88, 919.
[24] a) M. Murray, R. Schmutzler, E. Gründemann, H. Teichmann, J. Chem.
Soc. B 1971, 1714; b) B. L. Booth, K. O. Jibodu, M. F. Proença, J. Chem.
Soc., Chem. Commun. 1980, 1151.
[25] a) R. Schmutzler, J. Chem. Soc. 1964, 4551; b) J. H. Cameron, A. J.
McLennan, D. S. Rycroft, J. M. Winfield, J. Fluorine Chem. 1981, 19, 135.
[26] a) A. Peter, S. M. Fehr, V. Dybbert, D. Himmel, I. Lindner, E. Jacob, M.
Ouda, A. Schaadt, R. J. White, H. Scherer et al., Angew. Chem. 2018,
130, 9605; Angew. Chem. Int. Ed., 2018, 57, 9461; b) G. A. Olah, T. E.
Kiovsky, J. Am. Chem. Soc. 1968, 90, 4666.
[27] E. P. L. Hunter, S. G. Lias, J. Phys. Chem. Ref. Data 1998, 27, 413.
[28] T. B. McMahon, T. Heinis, G. Nicol, J. K. Hovey, P. Kebarle, J. Am. Chem.
Soc. 1988, 110, 7591.
This article is protected by copyright. All rights reserved.

10.1002/anie.201904007
Angewandte Chemie International Edition
COMMUNICATION
COMMUNICATION
A
new chloronium containing salt
Sebastian Hämmerling, Günther Thiele,
Simon Steinhauer, Helmut Beckers,
Carsten Müller, Sebastian Riedel*
[Me2Cl][Al(OTeF5)4]is synthesized on a
multigram-scale by means of a simple
one-pot procedure. The isolated
product can be handled at room
temperature and used as a strong
electrophilic methylation agent. This is
demonstrated by the methylation of the
very weak bases P(CF3)3, PF3, MeI and
MeBr.
Page No. – Page No.
A Very Strong Methylation Agent:
[Me2Cl][Al(OTeF5)4]
((Insert TOC Graphic here))
This article is protected by copyright. All rights reserved.