Ionic TEMPO in Ionic Liquids: Specific Promotion of the Aerobic Oxidation of Alcohols

Article abstract of DOI:10.1002/cctc.201600491

The main objective of this study was to design a recyclable TEMPO (2,2,6,6-tetramethylpiperidinyl-N-oxyl) derivative that could be used as a catalyst in an ionic liquid solvent for the aerobic oxidation of alcohols by using NaNO₂ and HCl as co-catalysts. To this end, a TEMPO derivative bearing a quaternary ammonium group, [4-Bu₂MeN-TEMPO][PF₆] (1), was prepared. It was subsequently shown that this ionic TEMPO derivative is an efficient catalyst for the aerobic oxidation of a variety of primary and secondary alcohols. It exhibits a synergistic effect with ionic liquid solvents and readily outperforms analogous oxidations in methylene chloride. Moreover, the ionic TEMPO could be recycled five times with no loss of activity.

Full text of DOI:10.1002/cctc.201600491

DOI: 10.1002/cctc.201600491
Full Papers
Ionic TEMPO in Ionic Liquids: Specific Promotion of the
Aerobic Oxidation of Alcohols
[
a]
[a]
[a]
[a]
Tsunehisa Hirashita,* Makoto Nakanishi, Tomoya Uchida, Masakazu Yamamoto,
[a]
[b]
[b, c]
Shuki Araki, Isabel W. C. E. Arends, and Roger A. Sheldon*
The main objective of this study was to design a recyclable
TEMPO (2,2,6,6-tetramethylpiperidinyl-N-oxyl) derivative that
could be used as a catalyst in an ionic liquid solvent for the
It was subsequently shown that this ionic TEMPO derivative is
an efficient catalyst for the aerobic oxidation of a variety of pri-
mary and secondary alcohols. It exhibits a synergistic effect
with ionic liquid solvents and readily outperforms analogous
oxidations in methylene chloride. Moreover, the ionic TEMPO
could be recycled five times with no loss of activity.
aerobic oxidation of alcohols by using NaNO and HCl as co-
2
catalysts. To this end, a TEMPO derivative bearing a quaternary
ammonium group, [4-Bu MeN-TEMPO][PF ] (1), was prepared.
2
6
Introduction
The selective oxidation of alcohols is one of the most impor-
catalysed by TEMPO and nitrite or its precursor has been
[
1]
[5]
tant reactions in organic synthesis. There is a growing con-
cern to develop greener oxidation processes that eliminate the
need for a stoichiometric amount of toxic heavy metals. The
introduced in this field. However, these reactions are normal-
ly performed in aqueous biphasic systems using methylene di-
[4e]
chloride as the organic phase. Hence, from the point of view
of green chemistry, the design of a greener protocol for this
oxidation is necessary.
[
2]
2
,2,6,6-tetramethylpiperidinyl-N-oxyl (TEMPO)-catalysed oxida-
tion of alcohols has emerged as a clean and economical oxida-
tion process using bleach or dioxygen as terminal oxidizing
Ionic liquids have been used as alternative to organic sol-
vents owing to their low vapour pressure; safety issues associ-
ated with the flammability of mixtures of oxygen and volatile
organic solvents in the gas phase can thus be circumvented.
Moreover, ionic liquids have the potential to immobilise cata-
[
3]
agents. In general, TEMPO-catalysed oxidations proceed with
high chemoselectivity; the over-oxidation of aldehydes to car-
boxylic acids is very slow because TEMPO prevents auto-oxida-
[
4]
tion under aerobic conditions.
[6]
Because of its high atom efficiency, oxygen (air) is usually
the oxidant of choice and aerobic oxidations are considered
one of the greenest oxidation processes; however, they are
usually performed with the aid of a catalytic amount of transi-
tion-metal compounds. Metal contamination of products
causes serious issues in the field of fine chemicals and pharma-
ceuticals manufacture. The best way to avoid this contamina-
tion is to eliminate the need for metal catalysts for oxidative
processes. Recently, an appealing aerobic oxidation of alcohols
lysts and recycle them for further reaction. The metal-free
aerobic oxidation of alcohols with recyclable catalysts immobi-
lised in ionic liquids is a desirable method for the preparation
of aldehydes and ketones. The TEMPO-catalysed oxidation in
ionic liquids and the recyclability of the ionic liquids in the pro-
[7]
cess have been successfully examined in the literature.
Because TEMPO is a rather expensive material, a technique
that facilitates its separation from the products and its reuse
should be considered. However, extraction of the reaction
products from the ionic liquid with an organic solvent results
in leaching of TEMPO, which prevents its recycling. To over-
come this difficulty, TEMPO derivatives containing polar func-
[a] Dr. T. Hirashita, M. Nakanishi, T. Uchida, M. Yamamoto, Prof. S. Araki
Graduate School of Engineering
Nagoya Institute of Technology
Gokiso-cho, Showa-ku, Nagoya 466-8555 (Japan)
E-mail: hirasita@nitech.ac.jp
[8]
tionalities have been tested. Besides their recyclability, the
use of ionic liquids as media for the aerobic oxidation of alco-
hols catalysed by a stable N-oxy radical, has not been system-
[
b] Prof. I. W. C. E. Arends, Prof. R. A. Sheldon
Biocatalysis and Organic Chemistry
Delft University of Technology
Julianalaan 136
[7e,8a,9]
atically investigated.
Herein, we report an expeditious
aerobic oxidation of alcohols catalysed by NaNO /HCl by using
2
a suitable ionic liquid and a TEMPO derivative bearing an am-
monium moiety. The recyclability of the ionic liquid and cata-
lyst is also discussed.
2
628 BL Delft (The Netherlands)
[c] Prof. R. A. Sheldon
School of Chemistry
University of the Witwatersrand
Johannesburg 2050 (Republic of South Africa)
Supporting information for this article can be found under:
http://dx.doi.org/10.1002/cctc.201600491.
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to that of the reaction performed in [bmim][NTf ] (entries 4
Results and Discussion
2
and 5). In a blank experiment in [bmim][PF ], benzaldehyde
6
was not detected, instead benzoic acid was formed in 4%
yield and 2a was recovered almost quantitatively. These results
demonstrate the importance of the proper choice of ionic
liquid in promoting the oxidation reaction.
Synthesis of [4-Bu MeN-TEMPO][PF ] (1)
2
6
To recycle the catalyst in the ionic liquid, an ammonium tag
was introduced into TEMPO (Scheme 1). The ionic TEMPO
1
was prepared by alkylation of 4-amino-TEMPO with n-butyl
iodide, followed by quaternisation with MeI. Ion exchange
with KPF gave [Bu MeN-TEMPO][PF ] as a pale-orange solid in
Effect of ammonium tag and solvent
6
2
6
[
10]
good yield.
To clarify the conditions for a faster oxidation, a set of reac-
tions was performed in [bmim][PF ] and CH Cl (Table 2). Com-
6
2
2
[
a]
Table 2. Solvent and catalyst effect on the oxidation of 2a.
[
b]
À1
Entry
Catalyst
Solvent
Time [h]
Yield [%]
TOF [h ]
1
2
3
4
1
1
[bmim][PF
6
6
]
]
1
10
10
13
99
33
CH
[bmim][PF
CH Cl
2
Cl
2
49 (51)
27 (64)
77 (23)
1.6
0.9
2.0
TEMPO
TEMPO
2
2
[
a] Reaction conditions: 2a (0.50 mmol), TEMPO or
1
(0.015 mmol),
(0.025 mmol), 1m HCl (0.050 mmol), solvent (ionic liquid: 1.5 mL
Cl : 5 mL), air, RT. [b] GC yield. Values in parentheses show the re-
NaNO
or CH
2
2
2
covery of 2a.
Scheme 1. Synthesis of [4-Bu
2
6
MeN-TEMPO][PF ] (1).
pared with the reaction using TEMPO 1 in [bmim][PF ], oxida-
6
tion in CH Cl was found to be sluggish, affording benzalde-
2
2
hyde in only 49% yield in 10 h (entry 2). In contrast, if TEMPO
Catalytic activity of 1 in aerobic oxidation
was used, better results were obtained in CH Cl2 (entry 3).
2
We first examined the oxidation of benzyl alcohol (2a) using
Under the conditions reported in reference [5e], the corre-
sponding aldehyde was obtained in 77% yield, although
a longer reaction time (13 h) was needed (entry 4).
3
mol% of ionic TEMPO 1, 5 mol% of NaNO and 10 mol% of
2
HCl in [bmim][PF ] (bmim=1-butyl-3-methylimidazolium). Ben-
6
zaldehyde was obtained in 99% yield in 1 h (Table 1, entry 1).
To confirm the importance of the ammonium group bound
to TEMPO, the reaction was performed in the presence of the
individual components: the oxidation of 2a in the presence of
TEMPO and tetrabutylammonium hexafluorophosphate gave
benzaldehyde in a lower yield compared with that obtained by
using catalyst 1 (Scheme 2).
In [bmim][NTf ], a slower oxidation rate was observed than
2
in [bmim][PF ] (entry 2), and a high yield can be obtained by
6
simply prolonging the reaction time (entry 3). The reaction in
[
bmpy][PF ] showed a lower oxidation rate, with a trend similar
6
[
a]
Table 1. Oxidation of 2a with 1.
[
b]
Entry
Solvent
Time
Yield of
Aldehyde [%]
Recovery
of 2a [%]
4 6
Scheme 2. Oxidation of 2a with TEMPO in the presence of [Bu N][PF ].
[
b]
[c]
[h]
1
2
3
4
5
[bmim][PF
[bmim][NTf
[bmim][NTf
6
]
1
1
16
1
16
1
99
53
99
52
99
0
43
0
40
0
2
2
]
]
These results clearly indicate that the use of ionic TEMPO
in the ionic liquid is crucial for increasing the oxidation rate.
1
[bmpy][PF
[bmpy][PF
[bmim][PF
6
]
]
]
6
[
d]
e
6
6
0
83
Aerobic oxidation of alcohols with 1
[
(
=
a] Reaction conditions: 2a (0.50 mmol),
0.025 mmol), HCl (0.050 mmol) in ionic liquid (0.5 mL), air, RT. [b] bmim
1-butyl-3-methylimidazolium; bmpy 1-butyl-4-methylpyridinium.
c] GC yield. [d] Without 1. [e] Benzoic acid was obtained in 4% yield.
1
(0.015 mmol), NaNO
2
Having established the optimum conditions, the scope and
limitations were examined by using a series of alcohols
=
[
(
Figure 1). The results are summarised in Table 3. Benzylic
&
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oxidation of unsaturated aliphatic alcohol 9 afforded the corre-
sponding aldehyde in moderate yield (entry 12). b-Phenethyl
alcohol (10) gave predominantly the corresponding acetal 12
(
entry 13). Using oxygen instead of air in [bmim][NTf ] under
2
heating was found to accelerate the reaction: phenylacetalde-
hyde was obtained in moderate yield and formation of acetal
12 was suppressed, presumably by the faster oxidative process
(
entry 14).
Thus, the optimum ionic liquid for this reaction depends on
the alcohol employed. Whereas [bmim][PF ] was preferable for
6
the oxidation of 2a as shown in Table 1, the use of [bmim]
[
NTf ] resulted in the selective oxidation of a primary aliphatic
2
Figure 1. Selected alcohol substrates.
Table 3. Oxidation of various alcohols.
alcohol (Table 3, entry 9).
[
a]
Aerobic oxidation of octan-2-ol with 1
We next tested the oxidation of 7, as a representative aliphatic
secondary alcohol, in a series of ionic liquids with different
anionic counterparts (Table 4). In contrast to the case of pri-
[
b]
[c]
Entry
Alcohol
Conditions
Time [h]
Yield [%]
[
d]
1
2
3
4
5
6
7
8
9
1
2a
2b
3a
3b
4
5
5
6
6
7
8
9
10
10
3:5:10
3:5:10
5:10:10
5:10:10
5:10:20
5:10:20
5:10:20
5:8:16
5:8:16
5:8:16
5:10:20
5:8:16
5:8:16
5:8:16
1
1
1
16
2
5
16
5
5
5
3
99
99
98
90 (2)
99
mary alcohols, [bmim][PF ] was superior to [bmim][NTf ] (en-
6
2
tries 1 and 2) and to [bmim][BF ], which resulted in slow oxida-
4
tion (entry 3). Ionic liquid [bmim][OTf] was also suitable for the
79 (12)
92
oxidation of 7 (entry 4).
36 (13), 11: 51
68 (22)
[
e]
[
a]
0
91
99
50 (19)
Table 4. Oxidation of 7 with 1 in ionic liquids.
1
1
[
b]
[b]
1
1
1
2
3
4
5
5
5
Entry
Solvent
Yield of 2-octanone [%]
Recovery of 7
18 (21), 12: 56
59 (13)
1
2
3
4
[bmim][PF
6
]
2
]
91
78
69
91
0
0
24
0
[e,f]
[bmim][NTf
[bmim][BF
[bmim][OTf]
[
a] Reaction conditions: alcohol (0.50 mmol) in [bmim][PF
6
] (1.5 mL) under
4
]
2
air at RT. [b] 1/NaNO /HCl (mol%). [c] Determined by GC. Values in paren-
theses show the recovery of the starting alcohol. [d] Entry 1 in Table 1.
e] In [bmim][NTf ]. [f] Performed under O (balloon pressure) at 608C.
[
a] Reaction conditions:
7
(0.50 mmol),
1
(0.015 mmol), NaNO
2
[
2
2
(
0.025 mmol), HCl (0.050 mmol), ionic liquid (1.5 mL) under air atmos-
phere at RT for 5 h. [b] GC yield.
Recyclability of 1
alcohols 2a, 2b and 3a were easily oxidised to the corre-
sponding aldehydes in high yields (entries 1–3), whereas ben-
zylic alcohol 3b with an electron-withdrawing group was sig-
nificantly less reactive (entry 4). Allylic alcohol 4 was converted
to cinnamaldehyde in good yield (entry 5). Normally, cyclic sec-
ondary alcohol 5 resists oxidation because of steric factors: for
instance, the TEMPO-catalysed reaction in CH Cl generates cy-
Next, the recyclability of the catalytic system was examined in
the oxidation of 2a. After the first run, the product was sepa-
rated from the ionic liquid layer by extraction with diethyl
ether. The ionic liquid containing ionic TEMPO 1 was directly
reused for the next oxidation. Although addition of new
NaNO and HCl was required, no decrease in yield was ob-
2
served up to five recycles (Table 5).
2
2
clohexanone only with 37% conversion and with 91% selectiv-
[
5e]
ity after 24 h. In contrast, the present method afforded cy-
clohexanone in high yields, although a longer reaction time
Stoichiometric oxidation
was required (entries 6 and 7). In [bmim][PF ], aliphatic alcohol
To gain insight into the catalytic role of 1, oxidation of 2a
6
+
6
was mainly converted into acetal 11, originating from the re-
using a stoichiometric amount of oxoammonium 1 was
+
action of the formed aldehyde with 6 (entry 8). The formation
tested. Oxoammonium 1 was prepared according to the liter-
+
[12]
of acetal in a protic ionic liquid has been previously report-
ature procedure described for [TEMPO ][BF ]. After exposure
4
[
11]
[13]
ed; however, this side reaction can be suppressed by switch-
of 1 to HPF6, the reaction mixture was treated with NaOCl.
ing the ionic liquid to [bmim][NTf ], which affords the corre-
The purity of the resulting oxoammonium salt was estimated
2
+
sponding aldehyde in moderate yield (entry 9). Secondary ali-
phatic alcohols 7 and 8 were converted into the corresponding
ketones in excellent yields (entries 10 and 11). Moreover, the
by oxidation of an excess amount of benzyl alcohol. TEMPO
obtained by this procedure showed good purity (98%), where-
as the oxoammonium derived from 1 was only 46% pure
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Comparison of TEMPO and ionic TEMPO (1) in ionic liquids
Table 5. Recycling of ionic TEMPO 1 and [bmim][PF
6
] for the oxidation of
[
a]
2
a.
For the catalytic and stoichiometric oxidations, CH Cl , which is
2
2
[
b]
[b]
Run
Yield [%]
Recovery of 2a [%]
typically used for TEMPO-catalysed reactions, was a superior
1
2
3
4
5
6
99
99
99
98
95
92
0
0
0
0
0
0
solvent to [bmim][PF ]. The oxidation in acetonitrile also yield-
6
ed better results than those obtained in [bmim][PF ]. This is in
6
[9a]
good agreement with the literature reports, which ascribe
this tendency to the different viscosities of molecular solvents
+
and ionic liquids. In contrast, TEMPO -mediated oxidations in
an alternative ionic liquid, N-butyl-N-methyl pyrrolidinium
[
(
a] Reaction conditions: 2a (0.50 mmol),
1
(0.015 mmol), NaNO
2
0.025 mmol), HCl (0.050 mmol), [bmim][PF ] (1.5 mL), air, RT for 1 h. The
6
bis(trifluoromethylsulfonyl)imide, proceeded faster those in
[
9b]
ionic phase recovered from the previous reaction was used. NaNO
0.025 mmol) and HCl (0.050 mmol) were added. [b] GC yield.
2
acetonitrile,
suggesting that the reaction rate of the
(
+
TEMPO -mediated oxidation is strongly dependent on the
ionic liquid employed. On the other hand, the results related
to the use of 1 were found to be quite different. The reactions
in [bmim][PF ] proceeded at a clearly faster rate than those
6
performed in CH Cl , and approximately the same results were
2
2
obtained in acetonitrile. This trend can be rationalized by as-
suming that more polar solvents preferably promote the for-
+
mation and reaction of the highly active oxoammonium 1
containing both oxoammonium and ammonium groups,
[
14]
thus compensating for the high viscosity of the ionic liquid.
Compared with the ionic liquid, acetonitrile served as a good
solvent, giving the same level of conversion. However, [bmim]
[
PF ] is superior to acetonitrile in separating the products from
6
the reaction mixture while keeping the catalyst in the solvent
to be reused in the next reaction.
Scheme 3. Preparation of oxoammonium salts.
(
Scheme 3). However, a satisfactory result was obtained by
+
Conclusions
using a double amount of reagents (88% purity of 1 ).
+
+
Stoichiometric oxidation of 2a with TEMPO or 1 was per-
TEMPO derivative 1 proved to be an effective mediator for the
aerobic oxidation of alcohols in ionic liquids. This study clearly
demonstrates the importance of careful screening of ionic liq-
uids with respect to the selectivity as well as the acceleration.
In addition, a strong synergistic effect between ionic TEMPO
formed in CH Cl , CH CN and [bmim][PF ], and the results are
2
2
3
6
summarised in Table 6.
1
and ionic liquids became apparent. The use of 1 and an
+
+ [a]
Table 6. Stoichiometric oxidation of 2a with TEMPO or 1 .
ionic liquid plays a key role in increasing the oxidation rate.
The ammonium tag on 1 is responsible not only for recycling
the N-oxy radical in the ionic liquid phase but also for enhanc-
ing the oxidation rate.
Entry
Oxidant
Solvent
Time
h]
Yield of
aldehyde [%]
Recovery
of 2a [%]
[
b]
[b]
[
+
1
2
3
4
5
6
1
1
1
[bmim][PF
6
]
]
0.25
0.25
1.5
1.5
1.5
96
100
64
23
70
0
0
36
66
24
6
+
CH
CH
3
2
CN
Cl
+
2
+
TEMPO
TEMPO
TEMPO
[bmim][PF
6
+
+
CH
CH
3
2
CN
Cl
2
1.5
92
Experimental Section
+
+
[
a] Reaction conditions: 2a (0.09 mmol), TEMPO or 1 (0.10 mmol) in
General methods
solvent (1.0 mL) at RT. [b] Determined by GC.
IR spectra were recorded with a JASCO IRA-102 spectrophotome-
1
ter. H NMR spectra were obtained in CDCl3 or CD CN by using
3
a Varian Mercury 300 spectrometer (300 MHz) with Me Si as inter-
4
nal standard; J values are given in Hz. GC analyses were performed
with a SHIMADZU GC-14B and GC-2014 fitted with a capillary
column and a flame ionization detector. Elemental analyses were
performed with a PerkinElmer 2400II analyser. Melting points were
measured with a Yanaco MP 50533 and are uncorrected. Ionic liq-
uids were purchased from Kanto Chemical and were used as re-
ceived. All alcohols were commercially available and distilled
before use.
Comparison of the results in Tables 2 and 6 reveals a similar
tendency in the stoichiometric and catalytic oxidations. The re-
+
action with 1 in CH CN and [bmim][PF ] proceeded faster
3
6
+
than that in CH Cl (entries 1–3), whereas TEMPO was most
2
2
+
efficient in CH Cl (entries 4–6). Notably, 1 was not completely
2
2
dissolved in CH Cl , and therefore the above results may not
2
2
+
accurately reflect the reaction rate of 1 in CH Cl .
2
2
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Experimental procedures
Octanal dioctyl acetal
1
Preparation of 4-Bu N-TEMPO
H NMR (300 MHz, CDCl
): d=0.86–0.90 (m, 9H), 1.2–1.4 (m, 30H),
3
2
1
.54–1.59 (m, 6H), 3.39–3.44 (m, 2H), 3.53–3.57 (m, 2H), 4.46 ppm
A mixture of 4-amino-TEMPO (1.62 g, 9.45 mmol), n-butyl iodide
13
(t, J=5.7 Hz, 1H); C NMR (75 MHz, CD CN): d=14.23, 22.81, 23.13,
3
(
4.5 mL, 39.6 mmol) and K CO (8.23 g, 59.5 mmol) in acetonitrile
2 3
2
6
4.95, 26.43, 29.40, 29.44, 29.59, 30.05, 30.46, 31.94, 31.99, 33.56,
5.50, 103.23 ppm.
(
50 mL) was heated at reflux for 23 h. The product was diluted
with diethyl ether (150 mL), washed with water (40 mLꢁ3) and
brine and dried over Na SO . The solvent was removed under re-
2
4
duced pressure to give 4-Bu N-TEMPO (2.38 g, 89%). R =0.82
2
f
Phenylacetaldehyde diphenetyl acetal
1
(
SiO /EtOH); H NMR spectra were recorded after addition of phe-
2
1
1
nylhydrazine (one drop) to the NMR sample tube. H NMR
H NMR (300 MHz, CDCl ): d=2.77–2.90 (m, 4H), 2.89 (d, J=5.7 Hz,
3
(
6
300 MHz, CDCl ): d=0.94 (t, J=7.1 Hz, 6H), 1.16 (s, 6H), 1.22 (s,
2H), 3.49–3.60 (m, 2H), 3.69–3.77 (m, 2H), 4.62 (t, J=5.7 Hz, 1H),
3
13
H), 1.30–1.42 (m, 4H), 1.46–1.71 (br s, 6H), 1.79–1.83 (m, 2H), 2.65
7.10–7.30 ppm (m, 15H); C NMR (75 MHz, CD CN): d=36.44,
3
13
(
br s, 4H), 3.17–3.22 ppm (m, 1H); C NMR (75 MHz, CDCl3):
40.68, 67.20, 104.10, 126.30, 126.42, 128.36, 128.42, 129.08, 129.70,
137.20, 139.06 ppm.
d=14.144, 19.925, 20.694, 31.234, 32.796, 41.227, 50.323, 50.371,
5
1
9
9.253 ppm; IR (neat): n˜ =3448, 2955, 2871, 2809, 1639, 1464,
376, 1362, 1328, 1287, 1243, 1217, 1195, 1089, 1074, 1035, 937,
À1
+[12]
03, 867, 735, 680 cm .
Preparation and titration of TEMPO
HPF (65 wt%, 115 mL, 0.50 mmol) was slowly added to a mixture
6
of TEMPO (78.6 mg, 0.50 mmol) and water (0.2 mL) over a period
of 3 min at room temperature. After stirring for 40 min, NaOCl
(1.84m, 136 mL, 0.25 mmol) was added over 3 min at 08C, and the
mixture was stirred for a further 1 h. The product was filtered and
Preparation of [4-Bu MeN-TEMPO]I
2
4
-Bu N-TEMPO (2.24 g, 7.92 mmol) was treated with MeI (2.5 mL,
2
4
0 mmol) in acetonitrile (40 mL) and heated at reflux for 3 h. After
complete consumption of 4-Bu N-TEMPO, as monitored by TLC,
2
washed with cold aqueous 5% NaHCO , water and cold diethyl
3
+
the solvent was removed under reduced pressure affording
ether. After drying, [TEMPO ][PF ] was obtained as a bright yellow
6
1
[
4-Bu MeN-TEMPO]I (3.23 g, 96%). R =0.78 (Al O /EtOH). H NMR
2
f
2
3
solid (88 mg). A mixture of benzyl alcohol (11.4 mL, 0.11 mmol) and
+
spectra were recorded after addition of phenylhydrazine (one
[
TEMPO ][PF ] (15.2 mg, 0.050 mmol) in CH Cl (4 mL) was stirred
6
2
2
1
drop) to the NMR sample tube. H NMR (300 MHz, CDCl ): d=1.03
3
at room temperature for 17 h. The product was extracted with
+
(
t, J=7.4 Hz, 6H), 1.23 (s, 6H), 1.32 (s, 6H), 1.44–1.60 (m, 4H), 1.68–
ether. The yield of benzaldehyde (98%) based on [TEMPO ][PF ]
6
1
3
1
.84 (m, 4H), 1.88 (d, J=12 Hz, 2H), 2.02 (d, J=9.6 Hz, 2H), 3.22 (s,
was determined by GC by using hexadecane as an internal
standard.
13
H), 3.30–3.62 ppm (m, 5H); C NMR (75 MHz, CDCl ): d=13.714,
3
9.678, 24.419, 32.479, 37.916, 46.840, 59.186, 59.597, 64.477 ppm;
À1
IR (KBr): n˜ =3434, 2962, 2867, 1633, 1463, 1362, 1245, 1195 cm .
+
Preparation and titration of 1
Preparation of ionic TEMPO 1
HPF (65 wt%, 115 mL, 0.50 mmol) was slowly added to a mixture
6
of 1 (111 mg, 0.25 mmol) and water (0.4 mL) over a period of 3 min
at room temperature. After stirring for 40 min, NaOCl (1.84m,
[
5
(
4-Bu MeN-TEMPO]I (2.15 g, 5.06 mmol) and KPF6 (1.06 g,
2
.74 mmol) were mixed in distilled water (40 mL) and acetone
40 mL) at room temperature for 3 h. The product was extracted
1
36 mL, 0.25 mmol) was added over 3 min at 08C, and the mixture
was stirred for a further 1 h. The product was filtered and washed
with methylene chloride, washed with water and brine and dried
over Na SO to give [4-Bu MeN-TEMPO][PF ] (1, 2.08 g, 93%).
R =0.80 (Al O /EtOH); m.p.: 167–1698C; H NMR and C NMR spec-
tra were recorded after addition of phenylhydrazine (one drop) to
the NMR sample tube. H NMR (300 MHz, CD CN): d=0.97 (t,
J=7.2 Hz, 6H), 1.14 (s, 6H), 1.18 (s, 6H), 1.32–1.40 (m, 4H), 1.64–
1
3
2
with cold aqueous 5% NaHCO , water and cold diethyl ether. After
3
2
4
2
6
+
drying, [1 ][PF ] was obtained as a yellow solid (118 mg). A mixture
of benzyl alcohol (10.4 mL, 0.10 mmol) and [1 ][PF ] (29.5 mg,
6
1
13
f
2
3
+
6
0
1
.050 mmol) in CH Cl (4 mL) was stirred at room temperature for
2 2
1
3
7 h. The product was extracted with ether. The yield of benzalde-
+
hyde (88%) based on [1 ][PF ] was determined by GC by using
6
.72 (m, 6H), 1.92–1.95 (m, 2H), 2.83 (s, 3H), 3.13–3.19 (m, 4H),
hexadecane as an internal standard.
13
.43–3.51 ppm (m, 1H); C NMR (75 MHz, CD CN): d=13.80, 19.56,
3
0.29, 24.77, 32.87, 38.31, 46.09, 59.69, 60.02, 65.18 ppm; IR (KBr):
n˜ =2970, 2879, 1637, 1469, 1384, 1368, 1243, 1198, 1105, 843, 741,
Stoichiometric oxidation of benzyl alcohol by ionic TEMPO
À1
+
6
79 cm ; HRMS (ESI ): m/z calcd for C H N O (cation): 298.2984;
18 38 2
+
À
1
(Table 6, entry 1)
found: 298.3002; HRMS (ESI ): m/z calcd for PF (anion): 144.9642;
6
found: 144.9636; elemental analysis calcd (%) for C H F N OP
18
38
6
2
A mixture of benzyl alcohol (10.2 mg, 0.094 mmol) and ionic
+
(
443.47): C 48.75, H 8.64, N 6.3; found: C 49.08, H 8.82, N 6.23.
TEMPO 1 (88% purity, 67 mg, 0.10 mmol) in [bmim][PF ] (1.0 mL)
6
was stirred at room temperature for 15 min. The product was ex-
tracted with diethyl ether (2 mLꢁ7). The yield was determined by
GC analysis by using hexadecane as an internal standard.
NaNO /HCl-mediated oxidation of alcohols catalysed by am-
2
monium TEMPO 1 (Table 1, entry 1)
A mixture of benzyl alcohol (52 mL, 0.50 mmol), NaNO2 (1.7 mg,
Acknowledgements
2
5 mmol), 1m HCl (50 mL) and ionic TEMPO 1 (6.7 mg, 3 mol%) in
[
bmim][PF ] (1.5 mL) was stirred at room temperature for 1 h. The
6
product was extracted with ether (5 mLꢁ5). The yield was deter-
mined by GC by using hexadecane as an internal standard.
This work was supported by the Overseas Advanced Educational
Research Practice Support Program from the Ministry of
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Received: April 26, 2016
Published online on && &&, 0000
&
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FULL PAPERS
Keeping the TEMPO: A recyclable
TEMPO (2,2,6,6-tetramethylpiperidinyl-N-
oxyl) derivative that can be used as cat-
alyst in ionic liquid solvent for the aero-
bic oxidation of alcohols by using
T. Hirashita,* M. Nakanishi, T. Uchida,
M. Yamamoto, S. Araki, I. W. C. E. Arends,
R. A. Sheldon*
&& – &&
NaNO and HCl as co-catalysts was de-
Ionic TEMPO in Ionic Liquids: Specific
Promotion of the Aerobic Oxidation of
Alcohols
2
signed. This ionic TEMPO derivative is
an efficient, recyclable catalyst for the
aerobic oxidation of a variety of primary
and secondary alcohols.
ChemCatChem 2016, 8, 1 – 7
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ꢀ 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
&
These are not the final page numbers! ÞÞ