Synthesis of 4-trimethylammonio-2,2,6,6-tetramethylpiperidine-1-yloxyl with various anions for investigation of ionic liquids

Article abstract of DOI:10.1016/j.tetlet.2008.03.073

A new synthetic way is described to prepare 4-trimethylammonio-2,2,6,6-tetramethylpiperidine-1-yloxyl bearing tetrafluoroborate, hexafluorophosphate or bis(trifluoromethylsulfonylimide) by an anion metathesis of 4-trimethylammonio-2,2,6,6-tetramethylpiperidine-1-yloxyl iodide using the corresponding silver salts. 4-Trimethylammonio-2,2,6,6-tetramethylpiperidine-1-yloxyl iodide is obtained by the methylation of 4-amino-2,2,6,6-tetramethylpiperidine-1-yloxyl with methyliodide. The new spin probe 4-trimethylammonio-2,2,6,6-tetramethylpiperidine-1-yloxyl bistrifluoromethylsulfonylimide and the spin probes containing tetrafluoroborate or hexafluorophosphate may be useful for an effective investigation of ionic liquids with similar anions.

Full text of DOI:10.1016/j.tetlet.2008.03.073

Available online at www.sciencedirect.com
Tetrahedron Letters 49 (2008) 3264–3267
Synthesis of 4-trimethylammonio-2,2,6,6-tetramethylpiperidine-1-yloxyl
with various anions for investigation of ionic liquids
a,
a
b
*
Veronika Strehmel , Hans Rexhausen , Peter Strauch
a University of Potsdam, Institute of Chemistry, Applied Polymer Chemistry, Karl-Liebknecht-Str. 24-25, D-14476 Potsdam-Golm, Germany
b University of Potsdam, Institute of Chemistry, Inorganic Chemistry, Karl-Liebknecht-Str. 24-25, D-14476 Potsdam-Golm, Germany
Received 16 February 2008; revised 11 March 2008; accepted 17 March 2008
Available online 20 March 2008
Abstract
A new synthetic way is described to prepare 4-trimethylammonio-2,2,6,6-tetramethylpiperidine-1-yloxyl bearing tetrafluoroborate,
hexafluorophosphate or bis(trifluoromethylsulfonylimide) by an anion metathesis of 4-trimethylammonio-2,2,6,6-tetramethylpiper-
idine-1-yloxyl iodide using the corresponding silver salts. 4-Trimethylammonio-2,2,6,6-tetramethylpiperidine-1-yloxyl iodide is obtained
by the methylation of 4-amino-2,2,6,6-tetramethylpiperidine-1-yloxyl with methyliodide. The new spin probe 4-trimethylammonio-
2,2,6,6-tetramethylpiperidine-1-yloxyl bistrifluoromethylsulfonylimide and the spin probes containing tetrafluoroborate or hexafluoro-
phosphate may be useful for an effective investigation of ionic liquids with similar anions.
Ó 2008 Elsevier Ltd. All rights reserved.
Keywords: Spin probes; ESR spectroscopy; Nitroxides; Ionic liquids
Ionic liquids are new solvents distinguishing from tradi-
tional solvents by their higher viscosity and their tunability
of solvent properties just by the variation of the cation or
the anion structure resulting in the name ‘designer sol-
vents’. Furthermore, ionic liquids are interesting for vari-
ous applications, such as in electrochemical devices, as
solvents for extractions and for reactions in organic, inor-
ganic, and polymer chemistry.1–7 The specific structure of
ionic liquids composed of cations and anions, and their
interactions with solutes may cause advantages of ionic liq-
uids compared to molecular solvents. However, the knowl-
edge about the properties of ionic liquids on a molecular
level and their interactions with solutes can be considered
as rare. Spin probes are a versatile tool to explore mole-
cular properties of these designer solvents in the molecular
domain.8–16 Positively or negatively charged spin probes
are crucial for the investigation of ionic liquids because
they directly interact with the individual ions of the ionic
liquids. Recently, we described an improved synthesis for
potassium 4-sulfonatooxy-2,2,6,6-tetramethylpiperidine-1-
yloxyl and sodium 4-sulfonatooxy-2,2,6,6-tetramethylpi-
peridine-1-yloxyl.16 These spin probes open the possibility
to study especially interactions with the cation of the ionic
liquid. This Letter describes the synthesis of 4-trimethylam-
monio-2,2,6,6-tetramethylpiperidine-1-yloxyl salts bearing
either bistrifluoromethylsulfonylimide, tetrafluoroborate
or hexafluorophosphate as anions, which can also function
as anions in ionic liquids. The selection of spin probes with
similar counter ions as ionic liquids will improve the solu-
bility of the spin probes in these ionic liquids and it will
eliminate the counter ion exchange of charged spin probes
dissolved in ionic liquids. Therefore, spin probes contain-
ing a similar counter ion as the investigated ionic liquid will
increase the efficiency of the investigation of ionic liquids
with spin probes.
4-Trimethylammonio-2,2,6,6-tetramethylpiperidine-1-yl-
oxyl iodide can be obtained by the methylation of
4-dimethylamino-2,2,6,6-tetramethylpiperidine-1-yloxyl or
4-amino-2,2,6,6-tetramethylpiperidine-1-yloxyl with methyl-
iodide.17–19 The latter19 cites a further reference, where
*
Corresponding author. Tel.: +49 331 977 5224; fax: +49 331 977 5036.
E-mail address: vstrehme@uni-potsdam.de (V. Strehmel).
0040-4039/$ - see front matter Ó 2008 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2008.03.073

V. Strehmel et al. / Tetrahedron Letters 49 (2008) 3264–3267
3265
the formation of another trimethylammonio substituted
radical is described by the reaction of a primary amino
substituted radical with methyliodide.20 Nevertheless, the
information about the experimental conditions to obtain
4-trimethylammonio-2,2,6,6-tetramethylpiperidine-1-yloxyl
iodide is rare in the literature.
Furthermore, exchange of the iodide can be done by
using KPF6 to obtain 4-trimethylammonio-2,2,6,6-tetra-
methylpiperidine-1-yloxyl hexafluorophosphate.21 How-
ever, no experimental details are given for this anion
exchange in the literature. Anion exchange is important
to tailor-made spin probes for the investigation of ionic
liquids. Therefore, we developed an improved procedure
for anion exchange of 4-trimethylammonio-2,2,6,6-tetra-
methylpiperidine-1-yloxyl iodide to obtain 4-trimethyl-
attributed to the presence of a small amount of the lithium
salt. Therefore, anion metathesis using silver bis-
trifluoromethylsulfonylimide is preferred because the
formed silver iodide precipitates, and it can be easily
removed resulting in 3 with a higher purity.
The spin probes are well soluble in dimethylsulfoxide.
The ESR spectrum of 3 dissolved in dimethylsulfoxide
consists of the expected three lines (Fig. 2), which are char-
acteristic for 2,2,6,6-tetramethylpiperidine-1-yloxyl deriva-
tives. Examples for ESR spectra of 3–5 dissolved in
1-butyl-3-methylimidazolium salts containing similar anions
as the spin probes are depicted in Figure 2 as well.
The ESR spectra of the spin probes in the ionic liquids
show line broadening and changes in the habitus in com-
parison with the ESR spectrum of 3 in dimethylsulfoxide
due to the stronger interactions between the spin probes
and the individual ions of the ionic liquids and the higher
viscosity of the ionic liquids. Furthermore, the observed
differences between the ESR spectra of the spin probes in
the ionic liquids may be attributed to the viscosity of these
ionic liquids that increase in the order 1-butyl-3-methyl-
ammonio-2,2,6,6-tetramethylpiperidine-1-yloxyl
deriva-
tives bearing similar counter ions as ionic liquids, such as
bistrifluoromethylsulfonylimide, tetrafluoroborate, and
hexafluorophosphate.
In a first step the commercially available 4-amino-
2,2,6,6-tetramethylpiperidine-1-yloxyl is converted into
4-trimethylammonio-2,2,6,6-tetramethylpiperidine-1-yloxyl
iodide by reaction with methyliodide (Fig. 1).22 Then,
anion metathesis of the iodide occurs when 4-trimethyl-
ammonio-2,2,6,6-tetramethylpiperidine-1-yloxyl iodide is
stirred with silver bistrifluoromethylsulfonylimide, silver
tetrafluoroborate or silver hexafluorophosphate in ace-
tone.23 High yields on the new spin probe 4-trimethyl-
ammonio-2,2,6,6-tetramethylpiperidine-1-yloxyl bistrifluoro-
methylsulfonylimide (3, mp 229–248 °C dec), 4-trimethyl-
ammonio-2,2,6,6-tetramethylpiperidine-1-yloxyl tetrafluo-
roborate (4, mp 259–268 °C dec), and 4-trimethyl-
ammonio-2,2,6,6-tetramethylpiperidine-1-yloxyl hexafluoro-
phosphate (5, mp 250–256 °C dec) are obtained because
silver iodide precipitates, and it can be easily separated
from the reaction mixture by the filtration resulting in
the crystalline 4-trimethylammonio-2,2,6,6-tetramethyl-
piperidine-1-yloxyl salts after the evaporation of acetone
in vacuo (Fig. 1).23
imidazolium
3-methylimidazolium
bistrifluoromethylsulfonylimide < 1-butyl-
tetrafluoroborate < 1-butyl-3-
methylimidazolium hexafluorophosphate.24,25 This is also
mirrored in the rotational correlation times (s) of the spin
probes (figure caption of Fig. 2) determined using the
method of Budil et al.26 The s values increase in the same
order as the solvent viscosity: dimethylsulfoxide < 1-butyl-
3-methylimidazolium bistrifluoromethylsulfonylimide < 1-
butyl-3-methylimidazolium tetrafluoroborate < 1-butyl-3-
methylimidazolium hexafluorophosphate.24,25,27 Moreover,
slight distinct values are obtained for the isotropic hyper-
fine coupling constant (Aiso(14N)) of the spin probes
dissolved in dimethylsulfoxide and in ionic liquids.
We can conclude from the synthetic work that anion
metathesis of 4-trimethylammonio-2,2,6,6-tetramethyl-
piperidine-1-yloxyl iodide using silver bistrifluoromethyl-
sulfonylimide, silver tetrafluoroborate and silver hexa-
fluorophosphate is an efficient way to obtain the
In principle, 3 can be obtained from 2 and lithium bis-
trifluoromethylsulfonylimide as well. However, purification
is difficult in this case, and a paste-like product is obtained.
The significant decrease in the melting point of 3 may be
corresponding
4-trimethylammonio-2,2,6,6-tetramethyl-
piperidine-1-yloxyl salts in a high yield. This new method
opens the possibility to make further ammonio substituted
spin probes with anions, which can be also found as the
Fig. 1. Formation of 4-trimethylammonio-2,2,6,6-tetramethylpiperidine-1-yloxyl iodide (2) by the methylation of 4-amino-2,2,6,6-tetramethylpiperidine-
1-yloxyl (1) with methyl iodide22 and anion metathesis using silver salts resulting in the cationic spin probes 3–5.23

3266
V. Strehmel et al. / Tetrahedron Letters 49 (2008) 3264–3267
and the DFG for financial support within the priority
programme SPP 1191.
References and notes
1. Wasserscheid, P.; Keim, W. Angew. Chem. 2000, 112, 3926.
2. Rogers, R. D.; Seddon, K. R. Ionic Liquids Industrial Applications to
Green Chemistry. ACS Symp. Ser. 818; American Chemical Society:
Washington, DC, 2002.
3. Wasserscheid, P.; Welton, T. Ionic Liquids in Synthesis; Wiley-VCH:
Weinheim, 2003.
4. Rogers, R. D.; Seddon, K. R.; Kubisa, P. Ionic Liquids as Green
Solvents. ACS Symp. Ser. 856; American Chemical Society: Wash-
ington, DC, 2003.
5. Rogers, R. D.; Brazel, C. S. Ionic Liquids in Polymer Systems. ACS
Symp. Ser. 913; American Chemical Society: Washington, DC, 2005.
6. Ohno, H. Electrochemical Aspects of Ionic Liquids; John Wiley &
Sons: Hoboken, New Jersey, 2005.
7. Wang, J.; Tian, Y.; Zhao, Y.; Zhuo, K. Green Chem. 2003, 5, 618.
8. Noel, M. A. M.; Allendoerfer, R. D.; Osteryoung, R. A. J. Phys.
Chem. 1992, 96, 2391.
9. Kawai, A.; Hidemori, T.; Shibuya, K. Chem. Lett. 2004, 11, 1464.
10. Kawai, A.; Hidemori, T.; Shibuya, K. Chem. Phys. Lett. 2005, 414,
378.
11. Evans, R. G.; Wain, A. J.; Hardacre, C.; Compton, R. G.
ChemPhysChem 2005, 6, 1035.
12. Stoesser, R.; Herrmann, W.; Zehl, A.; Strehmel, V.; Laschewsky, A.
ChemPhysChem 2006, 7, 1106.
13. Strehmel, V.; Laschewsky, A.; Stoesser, R.; Zehl, A.; Herrmann, W.
J. Phys. Org. Chem. 2006, 19, 318.
14. Grampp, G.; Kattnig, D.; Mladenova, B. Spectrochim. Acta A 2006,
63, 821.
15. Stoesser, R.; Herrmann, W.; Zehl, A.; Laschewsky, A.; Strehmel, V.
Z. Phys. Chem. 2006, 220, 1309.
16. Strehmel, V.; Rexhausen, H.; Strauch, P. Tetrahedron Lett. 2008, 49,
586.
17. Keith, A. D.; Snipes, W.; Mehlhorn, R.; Gunter, T. Biophys. J. 1977,
19, 205.
18. Hamada, K.; Iijima, T.; Mc Gregor, R. J. Polym. Sci. Phys. Ed. 1988,
26, 421.
19. Huang, W.; Charleux, B.; Chiarelli, R.; Marx, L.; Rassat, A.; Vairon,
J.-P. Macromol. Chem. Phys. 2002, 203, 1715.
20. Reid, D. A.; Bottle, S. E.; Micallef, A. S. Chem. Commun. 1998, 1907.
21. Aonuma, S.; Casellas, H.; Faulmann, C.; de Bonneval, B. G.;
Malfant, I.; Lacroix, P. G.; Cassoux, P.; Hosokoshi, Y.; Inoue, K.
Synth. Met. 2001, 120, 993.
Fig. 2. ESR spectra of
3
dissolved in (a) dimethylsulfoxide
(Aiso
containing similar anions as the spin probes: (b) 3 in 1-butyl-3-methyl-
imidazolium bistrifluoromethylsulfonylimide (Aiso
14N) = 15.7 G; s =
5.7 ns), (c) 4 in 1-butyl-3-methylimidazolium tetrafluoroborate (Aiso
14N) =
15.8 G; s = 9.9 ns), and (d) 5 in 1-butyl-3-methylimidazolium hexa-
fluorophosphate (Aiso
14N) = 15.4 G; s = 17.2 ns) at room temperature.
(
14N) = 15.5 G; s = 0.7 ns),26,28 and of 3–5 dissolved in ionic liquids
(
(
(
22. For the synthesis of 4-trimethylammonio-2,2,6,6-tetramethylpiper-
idine-1-yloxyl iodide (2), methyliodide from Aldrich (7 ml) is added to
4-amino-2,2,6,6-tetramethylpiperidine-1-yloxyl (1) from Acros
structural elements of ionic liquids. Such spin probes may
be of great interest for the study of ionic liquids. These spin
probes can be tailor made for ionic liquids, and possible
counter ion exchange with the ionic liquid anion can be
avoided. This should simplify the interpretation of results
obtained by the investigation of ionic liquids with spin
probes bearing cationic substituents.
(200 mg) dissolved in
a tert-butylmethylether methanol mixture
(10 ml: 10 ml) and stirred under nitrogen overnight. The 4-trimethyl-
ammonio-2,2,6,6-tetramethylpiperidine-1-yloxyl iodide precipitates
as red precipitate, which is filtered, washed with 10 ml tert-butyl-
methylether, and dried in vacuo (<40 °C, 1 mbar). The 4-trimethyl-
ammonio-2,2,6,6-tetramethylpiperidine-1-yloxyl iodide is obtained
with 28–39% yield (mass spectrometry: 214.2059 Da in the TOF MS
ES+ mode (calcd for C12H26N2O: 214.2045 Da) and 126.9453 Da in
the TOF MS ESÀ mode (calcd for IÀ: 126.9050 Da), mp 244–246 °C
dec determined by the microscopic observation of 2 during heating
and thermogravimetric analysis).
Acknowledgments
23. 4-Trimethylammonio-2,2,6,6-tetramethylpiperidine-1-yloxyl iodide
(100 mg) is stirred in 5 ml acetone under nitrogen at room temper-
ature. Then, a silver salt (113.8 mg silver bistrifluoromethylsulfonyl-
imide (Aldrich), 57 mg silver tetrafluoroborate (Aldrich) or 74.1 mg
silver hexafluorophosphate (Aldrich)) dissolved in 10 ml acetone is
dropped to the 4-trimethylammonio-2,2,6,6-tetramethylpiperidine-1-
yloxyl iodide acetone solution within 15 min. The reaction mixture is
The authors gratefully acknowledge A. Laschewsky for
the use of laboratory equipment, the group of E. Klein-
peter, especially I. Starke and S. Furstenberg from the
¨
University of Potsdam for mass spectrometric investiga-
tion, H. Wetzel from the Fraunhofer Institute for Applied
Polymer Research Potsdam-Golm for elementary analysis,

V. Strehmel et al. / Tetrahedron Letters 49 (2008) 3264–3267
3267
stirred for further 30 min in the case of the bistrifluoromethylsulf-
onylimide salt and for further 15 min in the case of the tetrafluoro-
borate and the hexafluorophosphate salts at room temperature and
then cooled at 0 °C for 12 h. The precipitate is filtered off resulting in
clear solutions. The acetone is evaporated from the clear solution (1 h
at 10 mbar) and dried in vacuo (1 mbar) for 2 h resulting in 90% yield
on the yellow to orange crystalline 4-trimethylammonio-2,2,6,6-
microscopic observation of 4 during heating and thermogravimetric
analysis), and 91% yield of yellow to orange crystalline 4-trimethyl-
ammonio-2,2,6,6-tetramethylpiperidine-1-yloxyl hexafluorophosphate
5 (mass spectrometry: 214.2040 Da in the TOF MS ES+ mode
(calcd for C12H26N2O: 214.2045 Da) and 144.8458 Da in the TOF MS
ESÀ mode (calcd for PF6À: 144.9642 Da), IR: characteristic vibration
for PF6 at 825 cmÀ1, mp 250–256 °C dec determined by the
À
tetramethylpiperidine-1-yloxyl bistrifluoromethylsulfonylimide
3
microscopic observation of 5 during heating and thermogravimetric
(mass spectrometry: 214.2034 Da in the TOF MS ES+ mode (calcd
for C12H26N2O: 214.2045 Da) and 279.6999 Da in the TOF MS ESÀ
mode (calcd for C2F6NO4SÀ2 : 279.9178 Da); elementary analysis:
34.00% C, 5.30% H, 8.24% N, 13.20% S (calcd for C14H26F6N3O5S2:
34.00% C, 5.30% H, 8.50% N, 12.97% S); IR: characteristic vibrations
for S–N–S (asymmetric vibration) at 1051 cmÀ1, –SO2– (symmetric
vibration) at 1137 cmÀ1, CF3 at 1188 cmÀ1, –SO2– (asymmetric
vibration) at 1330 cmÀ1 and 1345 cmÀ1, mp 229–248 °C dec deter-
mined by the microscopic observation of 3 during heating and
thermogravimetric analysis), 80% yield of yellow to orange crystalline
4-trimethylammonio-2,2,6,6-tetramethylpiperidine-1-yloxyl tetrafluo-
roborate 4 (mass spectrometry: 214.2039 Da in the TOF MS ES+
mode (calcd Àfor C12H26N2O: 214.2045 Da), IR: characteristic vibra-
tion for BF4 at 1035 cmÀ1, mp 259–268 °C dec determined by the
analysis).
24. Strehmel, V.; Laschewsky, A.; Wetzel, H.; Go¨rnitz, E. Macromole-
cules 2006, 39, 923.
25. Jin, H.; O’Hare, B.; Dong, J.; Arzhantsev, S.; Baker, G. A.; Wishart,
J. F.; Benesi, A. J.; Maroncelli, M. J. Phys. Chem. B 2008, 112, 81.
26. Budil, D. E.; Lee, S.; Saxena, S.; Freed, J. H. J. Magnet. Res. A 1996,
120, 155.
27. Ali, A.; Tewari, K.; Nain, A. K.; Chakravortty, V. Phys. Chem. Liq.
2000, 38, 459.
28. Methods: Mass spectra were taken in the ES+ and the ESÀ mode with
an ESI Q-TOF instrument. ESR spectra of the spin probes were
measured in X-band with
Thermogravimetric analysis was carried out using a Mettler-Toledo
TGA/SDTA 851e using a heating rate of 20 K/min.
a CW spectrometer E500 (Bruker).