TEMPO-derived task-specific ionic liquids for oxidation of alcohols

Article abstract of DOI:10.1055/s-2005-862396

A novel 2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPO) radical bearing an ionic liquid-type appendage has been prepared, and its catalytic activity for the selective oxidation of alcohols to the corresponding carbonyl compounds in ionic liquid-aqueous biphasic conditions has been investigated. The ionic liquid-supported TEMPO radical shows catalyst properties similar to those of nonsupported counterpart in terms of activity and selectivity, and can be easily recycled and reused without loss of activity and selectivity.

Full text of DOI:10.1055/s-2005-862396

LETTER
607
TEMPO-Derived Task-Specific Ionic Liquids for Oxidation of Alcohols
I
X
onic Liquids for
O
u
xidation of
A
e
lcohols -E Wu, Li Ma, Meng-Xian Ding, Lian-Xun Gao*
State Key Laboratory of Polymer Physics and Chemistry, Changchun Institute of Applied Chemistry, Chinese Academy of Science and
Graduate School of Chinese Academy of Sciences, Changchun, 130022, P. R. China
Fax +86(431)5697831; E-mail: lxgao@ciac.jl.cn
Received 13 December 2004
of reaction when compared to unsupported species. Fur-
Abstract: A novel 2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPO)
ther, with many polymeric supports a high proportion of
radical bearing an ionic liquid-type appendage has been prepared,
the reagent mass and volume serves solely as scaffolding
corresponding carbonyl compounds in ionic liquid-aqueous bipha- for the chemical functionality.
and its catalytic activity for the selective oxidation of alcohols to the
sic conditions has been investigated. The ionic liquid-supported
TEMPO radical shows catalyst properties similar to those of non-
Ionic liquids (ILs) have received recognition as novel and
16
promising solvents for synthetic chemistry. In parallel to
these uses a new class of reagents designed as task-specif-
ic ionic liquids (TSILs) has been developed: such deriva-
tives combine an IL-type part (in order to maintain the
corresponding physical properties) with an attached extra
function designed for the specific property.17 Another
very attractive possibility is to develop such TSILs as
alternatives to classical solid and soluble polymeric sup-
ports used in parallel. In contrast to classical solid and sol-
uble polymer-supported catalysts, these TSILs derivatives
are low molecular weight supports and should maintain
good mobility making their reactivity very close to solu-
tion chemistry. At the same time, the insolubility proper-
ties induced by the IL part of the molecule offers the
advantages of simply work up procedure and easy recov-
ery and recycling, which are usually associated with the
use of classical solid and soluble polymer-supported
TEMPO.
supported counterpart in terms of activity and selectivity, and can be
easily recycled and reused without loss of activity and selectivity.
Key words: ionic liquids, alcohols, carbonyl compounds, oxida-
tion, TEMPO
The oxidation of alcohols into the corresponding alde-
hydes or ketones is one of the most important functional
1
group transformations in organic synthesis. The use of
metal-free catalyst for selective oxidation of alcohols is
very appealing. The most useful ones are stable nitroxyl
radicals of the 2,2,6,6-tetramethylpiperidine-1-oxyl
2
3
(
TEMPO) derivatives that present low toxicity and an
4
interesting reversible redox behavior. Typically, such ox-
idations are carried out in the presence of 1 mol% of cat-
alyst and a stoichiometric amount of a terminal oxidant
such as bleach, sodium chlorite, N-chlorosuccinimide,
MCPBA according to the protocol introduced by Anelli,
5
6
7
8
9
Herein, we report the first time the synthesis of 4
Montanari and coworkers. However, the separation of
(
Scheme 1), a TEMPO derived TSIL, and its use as
products from TEMPO could require lengthy workup pro-
cedures in these systems, especially when reactions are
run on large scale.
catalyst for the metal-free, chemoselective oxidation of
To solve this problem, TEMPO has been immobilized
O
1
0
11
onto inorganic as well as organic supports affording
solid catalysts, which are readily separated from the reac-
tion mixtures. However, these solid catalysts are fraught
Cl
OH
O
a
1
2
with drawbacks of their own. On the other hand, the sol-
uble-polymers supported catalysis has gained increasing
attention in the last few years due to their feature conve-
nient solubility properties. Recent examples of soluble
polymer-supported TEMPO catalysts for the selective ox-
idation of alcohols include the polymer-immobilized pip-
N
O
1
N
O
2
O
O
N
N
N
N
1
3
eridinyl-oxyl, polymer-supported TEMPO obtained by
ring-opening metathesis polymerization (ROMP) of ni-
O
O
Cl –
PF6–
b
1
4
c
troxyl-functionalized norbornene monomers, and more
1
5
recently, a PEG-linker-TEMPO system has also been
described. However, the presence of the macromolecular
support has, in general, a detrimental effect up on the rates
N
O
N
O
3
4
Scheme 1 Synthesis of IL-supported TEMPO. Reagents and condi-
tions: (a) 4-hydroxy-TEMPO, chloroacetic acid, DMAP, DCC, 0 °C,
12 h, 92%; (b) 1-methylimidazole (1.4 equiv) 80 °C, 24 h in MeCN,
SYNLETT 2005, No. 4, pp 0607–0610
Advanced online publication: 22.02.2005
DOI: 10.1055/s-2005-862396; Art ID: U34204ST
0
4.
0
3.
2
0
0
5
98%; (c) KPF (1.2 equiv), r.t., 48 h in acetone, 96%.
6
©
Georg Thieme Verlag Stuttgart · New York

6
08
X.-E Wu et al.
LETTER
primary and secondary alcohols to aldehydes and ketones Table 1.22 As shown by quantitative GC analysis, alde-
1
8
in aqueous-[bmim]PF6 biphasic conditions, respec- hydes and ketones were formed in high yields from the
tively.
corresponding primary and secondary alcohols, respec-
tively.
Compound 4 has been prepared from commercially avail-
able 4-hydroxy-2,2,6,6-tetramethylpiperdine-1-oxyl as For comparison, we also evaluated the catalytic activity of
shown in Scheme 1. For the attachment of one TEMPO conventional non-immobilized TEMPO in aquoues IL bi-
1
9
unit, a general procedure was followed.
phase conditions under the same conditions and the result
is shown in Table 1, entry 11. It is found that the IL-sup-
ported TEMPO shows similar catalyst proprieties to the
non-supported TEMPO in terms of activity and selectivi-
ty, and offers the additional advantages of simplified
workup procedure and easy recovery and recycling.
The IL-suported TEMPO radical 4 was then applied as
catalyst in the oxidation of various alcohols according to
the Anelli protocol. The general procedure described in
reference 22 was applied for all oxidation runs. The most
significant results of this study are summarized in
2
1
Table 1 Oxidation of Alcohols by Ionic Liquid-Supported Nitroxyl Catalysts
NaOCl (1.24 equiv), KBr (10 mol%),
O
OH
4 (1 mol%), pH = 8.6
R1
R2
[bmim]PF6, H2O, 0 °C
R1
R2
Entry
1
Alcohol
Producta
Time (min)
5
Yield (%)b
94
OH
OH
O
O
2
3
Cl
Cl
5
5
95c
93
OH
O
O2N
O2N
4
5
6
5
5
95
96
96
OH
OH
O
O
OH
OH
O
O
10
7
8
9
10
10
95
88
OH
O
OH
O
5
5
5
90
86
95c
1
1
0
1
OH
O
OH
O
a
b
c
All the products were identified by GC-MS, IR, NMR and in comparison with authentic samples.
Selectivity >99% based on GC.
TEMPO was used as catalyst.
Synlett 2005, No. 4, 607–610 © Thieme Stuttgart · New York

LETTER
Ionic Liquids for Oxidation of Alcohols
609
We finally investigated the possibility of recycling the
catalyst. The recyclability of the used ILs solution con-
taining the catalyst was demonstrated for the oxidation of
benzyl alcohol to benzaldehyde under the same condi-
tions. After separation from the reaction products, the IL-
supported TEMPO was reused up to three times and the
results are summarized in Table 2. No variation of catalyt-
ic activity and selectivity of the recovered catalyst com-
pared to the fresh catalyst were observed.
(8) (a) Cella, J. A.; Kelley, J. A.; Kenehan, E. F. J. Org. Chem.
975, 40, 1860. (b) Cella, J. A.; McGrath, J. P.; Kelley, J.
A.; El Soukkary, O.; Hilpert, L. J. Org. Chem. 1977, 42,
077.
1
2
(
9) (a) Anelli, P. L.; Biffi, C.; Montanari, F.; Quici, S. J. Org.
Chem. 1989, 54, 2970. (b) Anelli, P. L.; Montanari, F.;
Quici, S. Org. Synth. 1990, 69, 212.
(10) (a) Heeres, A.; van Doren, H. A.; Gotlieb, K. F.; Bleeker, I.
P. Carbohydr. Res. 1997, 299, 221. (b) Bolm, C.; Fey, T.
Chem. Commun. 1999, 1795. (c) Brunel, D.; Lentz, P.;
Sutra, P.; Fajula, F.; Nagy, J. B. Stud. Surf. Sci. Catal. 1999,
125, 237. (d) Verhoef, M. J.; Peters, J. A.; van Bekkum, H.
Table 2 Reuse of the Catalyst Solution for the Oxidation of Benzyl
Stud. Surf. Sci. Catal. 1999, 125, 465. (e) Ciriminna, R.;
Blum, J.; Avnir, D.; Pagliaro, M. Chem. Commun. 2000,
1441. (f) Fey, T.; Fischer, H.; Bachmann, S.; Albert, K.;
Bolm, C. J. Org. Chem. 2001, 66, 8154.
Alcohol to Benzaldehyde
Entry Alcohol
1
Product
Time (min) Yield (%)a
5
5
5
95
95
93
(11) Dijksman, A.; Arends, I. W. C. E.; Sheldon, R. A. Chem.
Commun. 2000, 271.
12) (a) Cornils, B. Catalysis from A to Z: A Concise
Encyclopedia; Wiley-VCH: Weinheim, 2000. (b) Czarnik,
A. W. Solid Phase Organic Synthesis; Wiley: New York,
OH
OH
O
O
O
(
2
3
2001.
(
13) Dijksman, A.; Arends, I. W. C. E.; Sheldon, R. A. Chem.
Commun. 2000, 271.
OH
(
(
14) Tanyeli, C.; Gümüs, A. Tetrahedron Lett. 2003, 44, 1639.
15) Pozzi, C.; Cavazzini, M.; Quici, S.; Benaglia, M.;
Dell’Anna, G. Org. Lett. 2004, 6, 441.
a
Selectivity >99% based on GC.
(
16) Wasserscheid, P.; Welton, T. Ionic Liquids in Synthesis;
Wiley-VCH: Weinheim, 2003.
(
17) Wierzbicki, A.; Davis, J. H. Proceedings of the Symposium
on Advances in Solvent Selection and Substitution for
Extraction, 5-9 March 2000; AIChE: New York, 2000.
18) Fuller, R. T.; Carlin, H. C.; de Long, H. C.; Haworth, D. J.
Chem. Soc., Chem. Commun. 1994, 299.
In summary, a different approach to designing a recycla-
ble TEMPO catalyst using IL carrier for the selective
oxidation of alcohols in IL and aqueous biphasic media is
presently reported in this work. The new IL-supported
radical proved to be an efficient, selective and recoverable
catalyst for the selective oxidation of alcohols, and shows
catalyst properties similar to non-supported TEMPO in
terms of activity and selectivity. The facile recovering of
the catalyst is a great advantage of this method since it
allows its reuse without observing obvious decrease in re-
activity. Work is in progress to further address the recov-
erability and recyclability properties of this new ligand.
(
(
19) General Procedure for the Attachment of One TEMPO
Unit.
To a stirred solution of 4-hydroxy-2,2,6,6-tetramethyl-
piperdine-1-oxyl (1, 0.86 g, 5 mmol) and chloroactic acid
(
0.40 g, 5 mmol) in CH Cl (25 mL) at 0 °C under argon,
2 2
DCC (1.03 g, 5 mmol) and DMAP (0.15 g, 1.25 mmol) were
added and the reaction mixture was stirred for 12 h at r.t. The
solid materials formed were filtered off and the filtrate was
washed with 1 M HCl (5 mL) followed by sat. NaHCO (10
3
mL) and brine (10 mL). The organic phase was dried over
MgSO and evaporated under reduced pressure, and then
4
Acknowledgment
filtered through a short flash chromatography (EtOAc–
hexanes 1:4) providing chloroacetic acid 2,2,6,6-tetra-
methyl-1-oxy-piperidin-4-yl ester(2) as a red powder (1.14
g, 92%). Then 1-methylimidazole (0.46 g, 5.6 mmol) was
added to a solution of 2 (1.00 g, 4 mmol) in MeCN (30 mL)
and the resulting solution was stirred for 48 h at 80 °C. After
that, the solvent was removed in vacuum and the residue was
washed with acetone to give 3 as a light red powder (1.30 g,
The work was supported by the National Natural Science foundati-
on of China (no. 20174040 and 50333030).
References
(
(
(
(
(
(
1) Hudlicky, M. Oxidations in Organic Chemistry; American
Chemical Society: Washington DC, 1990.
2) Degonneau, M.; Kagan, E. S.; Mikhailov, V. I.; Rozantsev,
E. G.; Sholle, V. D. Synthesis 1984, 895.
3) LD50 (oral rat, 4-hydroxy-TEMPO) = 1053 mg Kg21; CAS
database.
4) de Nooy, A.; Besemer, A.; van Bekkum, H. Synthesis 1996,
98%). Compound 4 was prepared by stirring 3 (1.00 g, 3
mmol) with KPF (0.66 g, 3.6 mmol) in acetone (30 mL) at
6
r.t. for 48 h. After this, the insoluble by-products were
filtered off and the acetone was removed in vacuum to afford
4
as a pink powder (1.27 g, 96%). As excepted, this charged
TEMPO 4 is preferentially soluble in [bmim]PF and
6
35, 1153.
insoluble in water. All these novel compounds were stable in
5) Anelli, P. L.; Biffi, C.; Montanari, F.; Quici, S. J. Org.
Chem. 1987, 52, 2559.
6) Zhao, M.; Li, J.; Mano, E.; Song, Z.; Tschaen, D. M.;
Grabowski, E. J. J.; Reider, P. J. J. Org. Chem. 1999, 64,
1
13
air and characterized by H NMR, C NMR, FTIR spectro-
metry, mass spectrometry and elemental analyses ref. 20.
20) To samples containing nitroxyl radical residues was added
one drop of neat phenylhydrazine to the NMR sample tube
immediately prior to analysis in order to reduce in situ the
paramagnetic center to the corresponding hydroxylamine
species.
(
2564.
(
7) Einhorn, J.; Einhorn, C.; Ratajczak, F.; Pierre, J. L. J. Org.
Chem. 1996, 61, 7452.
Synlett 2005, No. 4, 607–610 © Thieme Stuttgart · New York

6
10
X.-E Wu et al.
LETTER
1
Compound 2: mp 55 °C. H NMR (400 MHz, CDCl ): d =
49.59, 43.41, 35.87, 32.09, 20.37. IR (KBr, selected data):
3
–
1
5
.14 (s, 1 H), 4.10 (s, 2 H), 1.97 (t, 2 H, J = 0.8 Hz), 1.83 (t,
1745.13, 1225.18, 1178.83, 839.76 cm . Anal. calcd for
C H F N O P: C, 40.91; H, 5.72; N, 9.54; P, 7.03. Found:
2
H, J = 1.2 Hz), 1.28 (s, 6 H), 1.14 (s, 6 H). 13C NMR (400
1
5
25
6
3
3
MHz, CDCl ): d = 20.37, 31.93, 41.21, 43.29, 68.47, 166.79.
C, 40.81; H, 5.62; N, 9.30; P, 7.23. MS (FAB): m/z calcd
[M] : 295.38; found: 294.9.
3
+
IR (KBr, selected data): 1751.93, 1204.23, 1161.84, 791.67
–
1
cm . Anal. Calcd for C H ClNO : C, 53.12; H, 7.70; Cl,
(21) Anelli, P. L.; Biffi, C.; Montanari, F.; Quici, S. J. Org.
Chem. 1987, 52, 2559.
(22) General Procedure for all Oxidation Runs.
An alcohol (0.80 mmol), 4 (0.008 mmol, 3.54 mg) and
dodecane (0.24 mmol) used as the internal standard in GC-
1
1
19
3
1
4.25; N, 5.63. Found: C, 53.17; H, 7.74; N, 5.67. MS (ESI):
+
m/z calcd [M] : 248.73; found: 248.40.
1
Compound 3: mp 191 °C. H NMR (400 MHz, DMSO): d =
9.14 (s, 1 H), 7.54 (s, 1 H), 7.36 (s, 1 H), 5.24 (s, 2 H), 5.04
(
s, 3 H), 3.90 (s, 3 H), 1.90 (t, 2 H, J = 0.8 Hz), 1.50 (t, 2 H,
analysis were dissolved in [bmim]PF (2 mL) followed by
0.16 mL aq KBr (0.5 M). After cooling the mixture at 0 °C,
2.7 mL of aq NaOCl diluted to a concentration of 0.37 M and
6
1
3
J = 1.2 Hz), 1.10 (s, 6 H), 1.07 (s, 6 H). C NMR (400 MHz,
DMSO): d = 166.43, 137.73, 123.66, 123.27, 68.92, 57.93,
4
9.54, 43.37, 35.89, 32.06, 20.32. IR (KBr, selected data):
buffered to pH 8.6 by NaHCO was added and the reaction
3
–
1
1
745.13, 1175.20, 1221.89 cm . Anal. calcd for
mixture stirred vigorously. After the oxidation, the IL phase
was separated and the resultant carbonyl compounds could
easily be separated from the IL medium by simple extraction
C H ClN O : C, 54.46; H, 7.62; N, 12.70. Found: C, 54.58;
H, 7.59; N, 12.72. MS (FAB): m/z calcd [M] : 295.38;
15
25
3
3
+
found: 294.7.
with Et O (4 × 5 mL), which was analyzed by GC. The IL
2
1
Compound 4: mp 53 °C. H NMR (400 MHz, DMSO): d =
containing catalyst can subsequently be re-used for a new
reaction cycle. The combined organic extracts were dried
with Na SO , and evaporated to dryness. The residue was
9.04 (s, 1 H), 7.36 (s, 1 H), 7.27 (s, 1 H), 5.20 (s, 2 H), 5.04
(
s, 3 H), 3.89 (s, 3 H), 1.91 (t, 2 H, J = 0.8 Hz), 1.50 (t, 2 H,
2
4
1
3
J = 1.2 Hz), 1.10 (s, 6 H), 1.08 (s, 6 H). C NMR (400 MHz,
DMSO): d = 166.38, 137.69, 123.68, 123.29, 69.09, 58.03,
purified by silica gel flash chromatography eluting with
EtOAc–petroleum ether.
Synlett 2005, No. 4, 607–610 © Thieme Stuttgart · New York