Synthetic utilities of ionic liquid-supported NHPI complex

Article abstract of DOI:10.1016/j.tetlet.2006.02.077

Ionic liquid (IL)-supported NHPI complex for the oxidation and/or nitration was prepared. Synthetic utilities of the complex as recoverable and recyclable system in ionic liquid were described.

Full text of DOI:10.1016/j.tetlet.2006.02.077

Tetrahedron Letters 47 (2006) 2797–2801
Synthetic utilities of ionic liquid-supported NHPI complex
Shinichi Koguchi and Tomoya Kitazume*
Graduate School of Bioscience and Bioengineering, Tokyo Institute of Technology, 4259 Nagatsuta-cho,
Midori-ku, Yokohama 226-8501, Japan
Received 27 January 2006; revised 10 February 2006; accepted 10 February 2006
Available online 3 March 2006
Abstract—Ionic liquid (IL)-supported NHPI complex for the oxidation and/or nitration was prepared. Synthetic utilities of the
complex as recoverable and recyclable system in ionic liquid were described.
Ó 2006 Elsevier Ltd. All rights reserved.
The concept of recoverable and recyclable catalysts has
become extremely important from both the environmen-
tal and economical points of view.1 Further, there is a
growing interest in the development of the greener
chemical processes that do not lead to three major
sources of waste: organic solvents, catalysts and any
hazardous by-products.2 Especially, nucleophilic and/
or oxidation reactions have been recognized as being
useful in organic synthesis, their reactions commonly
employ organic solvents (such as DMF, CH3CN,
DMSO, etc.), and in many cases they are removed from
the final reaction mixture by a water quench which leads
to an aqueous waste stream. Further, reusable media
(ionic liquids) are having an important impact on organ-
ic reactions,3 and various kinds of reactions in ionic liq-
uids have been reported until now.4 In this field, it has
been recognized that ionic liquid (IL)-supported catalyst
system is the major advantage in the homogeneous cat-
alytic processes as recoverable and recyclable system.5
To date, synthetic applications using ionic liquid (IL)-
supported materials have been based on a few methods:
(1) Rh-complex for the ring-closing reaction,6 (2) Bay-
lis–Hillman reaction,7 (3) Fructose-derived ionic liq-
uids,8 (4) IL-supported TEMPO or NHPI complex for
oxidation.9 Furthermore, in spite of the above men-
tioned pioneering complexes, their scope and limitation
of synthesis and synthetic utilities are an unsolved
problem.
able and recyclable system for the oxidation and nitra-
tion with HNO3.
Catalytic oxidation of carbohydrates using the stable
phthalimide N-oxy (PINO) radical has become one of
the most promising procedures to convert carbinols into
the corresponding carbonyl compounds.11–14 It is
known that N-hydroxy-phthalimide (NHPI) acts as a
catalyst for the transformation of alkanes to alcohols,
ketones, carboxylic acids, and/or nitroalkanes under
mild oxidation conditions.13,14 In our results of the oxi-
dation reaction from 1-phenyl ethanol to acetophenone
in the NHPI–Co(OAc)2–O2 system shown in Table 1,
the fluorinated ionic liquids are efficient for the oxida-
tion reaction using NHPI as a catalyst. However, yields
Table 1. Sovelt effect in the oxidation with NHPI
O
N
OH
O
O
OH
NHPI
Co(OAc)2/O2
80 oC/6 h
Entry
Solvent
Yielda (%)
1
2
3
4
[bmim][PF6]
[bmim][CF3SO3]
[bmim][BF4]
93
80
78
78
[bmim][(CF3SO2)2N]
In this letter, we would like to describe the utilities of
ionic liquid (IL)-supported NHPI complexes as recover-
5
6
7b
[bmim][NO3]
[bmim][CH3SO3]
Ethyl acetate
65
33
92
a Yields were determined by 1H NMR integral intensities using
C6H5CF3 as an internal standard.
b The reaction was carried out under reflux.
Keywords: Ionic liquid; Supported complex; Oxidation reaction.
*
Corresponding author. Tel.: +81 45 924 5754; fax: +81 45 924
5780; e-mail: tkitazum@bio.titech.ac.jp
0040-4039/$ - see front matter Ó 2006 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2006.02.077

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S. Koguchi, T. Kitazume / Tetrahedron Letters 47 (2006) 2797–2801
for signal of 19F NMR spectrum suggests a simple pat-
tern (doublet with a coupling constant: JF–P = 700–
730 Hz).10 In the 19F NMR spectrum of the above com-
plex 4, a signal of PF6 appears at d 92.4 ppm (4) from
ext. C6F6, and the coupling pattern of a signal of PF6
was doublet (4, d, JF–P = 716.5 Hz). From the results
Table 2. Reuse of catalyst and solvent system
OH
O
Co(OAc)2/O2
[bmim][PF6]
1
of the H, 19F, and 13C NMR spectra, the structure of
Run: yield (%)
1
2
3
4
5
this complex was identified. From the results of the oxi-
dation reaction from 1-phenyl ethanol to acetophenone
shown in Table 2, we have found that the system using
by the IL-NHPI (10 mol %)–Co(OAc)2–O2 in ionic
liquid ([bmim][PF6]; made in NIPPON GOHSEI (The
Nippon Synthetic Chemical Industry Co. Ltd)) is reus-
able. In the same system, various types of carbinols
are transformed into the corresponding aldehydes and/
or ketones in good yield shown in Table 3. Obviously,
secondary hydroxy group is selectively oxidized in this
system (entry 5).
NHPI (6 h)
IL-NHPI 4 (2 h)
93
98
80
99
26
96
98
97
drastically decreased from the first cycle (93%) to the
second (80%) and the third cycles (26%) shown in Table
2.
From these results, we have found that NHPI is sepa-
rated smoothly from ionic liquid with organic solvents,
and that it is impossible to construct the reusable reac-
tion system because of the disappearance of NHPI as
a catalyst. Therefore, we have designed the ionic
liquid-supported NHPI complex which offers several
benefits in comparison to homogeneous and/or hetero-
geneous catalysts, including easier product isolation
and purification and the possibility to reuse the system.
Ionic liquid (IL)-supported NHPI was prepared via the
synthetic routes shown in Scheme 1. The structure of
Table 3. Oxidation with complex
4
and Co(OAc)2 system in
[bmim][PF6]
Entry Substrate
Product
Time Yield
(h)
(%)
1
2
3
Heptanol
2-Nonanol
PhCH(Me)OH
Heptanal
2-Nonanon
PhCOMe
10
2
2
Trace
84
98
O
this complex was confirmed by the H and 13C NMR
1
4
5
cyclo-C6H11OH
2
2
80
78
spectra.
OH
O
In the literature,15 the crystal structure of 1-ethyl-3-
methylimidazolium hexafluorophosphate indicates PF6
unit related by symmetry elements, and then the report
OH
OH
O
O
O
O
H2N O
pyridine, 80 oC
OH
OH
N
O
BnO
O
O
1 (58%)
O
O
O
O
O
O
1) SOCl2
2) HOCH2CH2Cl
FeCl3
CH2Cl2
N
N
BnO
HO
O
O
Cl
Cl
(63%)
2 (60%)
O
O
O
O
N
NMe
Cl-
N
NMe
-
PF6
N
NMe
HPF6
O
OH
3 (quant.)
O
toluene
N
N
O
O
OH
4 (50%)
IL-supported NHPI
Scheme 1.

S. Koguchi, T. Kitazume / Tetrahedron Letters 47 (2006) 2797–2801
2799
The above reactions commonly employ organic solvents
(diethyl ether, methylene dichloride, etc.) for the extrac-
tion of the product, and in the above cases they are re-
moved from the final reaction product. However, from
the point of view on the greener chemical processes, it
is important that they do not lead to three major sources
of waste: organic solvents, catalysts and any hazardous
by-products.2 Therefore, instead of the organic solvents
for the extraction process, we examined other extraction
method. As it is well known that the supercritical carbon
dioxide is a useful medium for organic reaction and
extraction solvent, we examined the extraction of oxida-
tion products in IL-supported NHPI complex-ionic
liquid [bmim][PF6] with supercritical carbon dioxide. At
first, we have examined the relationship with tempera-
ture and percentage of extracted acetophenone in ionic
liquid [bmim][PF6]. From the results shown in Figure
1, we have found that the extraction proceeded
smoothly at 35 °C. Therefore, the oxidation reactions
in the pressure steel vessel were carried out at 80 °C.
After heating for 5 h, the product was extracted with
supercritical carbon dioxide at 35 °C shown in Figure
2, and then successive reuse of the recovered IL-sup-
ported NHPI complex-ionic liquid system and in the
same reaction yielded amounts of product as high as
in the first cycle. In the third cycle, reuse of reaction
system recovered from the second cycle is possible to
produce the same material in the same reaction. The
results in supercritical carbon dioxide extraction system
are shown in Table 4.16
In the next step, we examined the direct nitration of car-
bon–hydride bond. Nitration is an important process in
Table 4. Extraction with supercritical carbon dioxide
Entry
Substrate
Product
Yielda (%)
1
2
3
4
5
PhCH(Me)OH
PhCH(Me)OH
PhCH(Me)OH
2-Nonanol
cyclo-C6H11OH
OH
PhCOMe
PhCOMe
PhCOMe
2-Nonanon
cyclo-Hexanone
O
89
95b
86c
97
77
6
63
OH
OH
a Reaction condition: 1-phenyl ethanol (0.5 mmol), ionic liquid (5 mL),
IL-NHPI complex (0.05 mmol), 80 °C.
b Second cycle.
c Third cycle.
Table 5. Nitration with HNO3 in IL-complex 4 systema
Entry Alkane
1
Product
Time (h) Yield (%)
NO2
10
49
NO2
NO2
2b
10
10
10
40
70
50
100
90
80
70
60
50
40
30
20
10
3
NO2
4
0
10 15 20 25 30 35 40 45 50 55 60 65
a Reaction was carried out at 80 °C with 40% IL-supported NHPI
complex and 1.5 equiv HNO3.
b Second cycle.
Temperature (oC)
Figure 1.
Pressure
Mater
Pressure
Mater
Safety
Valve
40 ºC
Back
Pressure
Regulator
Pressure
Regulator
CO2
Temp. Controller
Cold Trap
Compound
Ionic Liquid
IL-Cat.
Compound
Figure 2.

2800
S. Koguchi, T. Kitazume / Tetrahedron Letters 47 (2006) 2797–2801
the organic synthesis.14 However, the temperature (250–
400 °C) for the nitration of alkanes using nitric acid
and/or NO2 is not convenient for the greener chemis-
try.15 Therefore, we examined the nitration of alkanes
in IL-supported NHPI complex (25 mol %)–HNO3–
ionic liquid [bmim][PF6] system. From the results shown
in Table 5, this reaction system is reusable (entries 1
and 2), and then the nitrations proceed at 80 °C
smoothly.
15. (a) Markofsky, S. B. In Ullmann’s Encyclopedia Industrial
Organic Chemicals; Wiley-VCH: Weinheim, 1999; Vol. 6,
p 3487; (b) Sakaguchi, S.; Nishiwaki, Y.; Kitamura, T.;
Ishii, Y. Angew. Chem., Int. Ed. 2001, 40, 222–224.
16. Ionic liquid-supported NHPI complex 4.
(a) 2-Chloroethyl 2-(benzyloxy)-1,3-dioxoisoindoline-5-
carboxylate 2.
A mixture of compound 1 (0.60 g, 2 mmol) and SOCl2
(6 ml) was stirred for 1 h at 50 °C, and then the excess
SOCl2 was removed under vacuum. Into the residue, 2-
chloroethanol (0.16 g, 2 mmol), pyridine (0.02 g,
0.2 mmol) and CH2Cl2 (10 ml) were added. After the
mixture was refluxed for 2 h, the solvent was removed
under vacuum. Product was extracted with ethyl acetate,
and the whole was washed with 1 N-HCl. After drying
over anhydrous MgSO4, the product was purified by
column chromatography on silica gel using a mixture of
ethyl acetate–hexane (1:5), giving the title material 2 (yield.
60%) as a colorless oil.
In conclusion, ionic liquid-supported systems are conve-
nient reaction reuse systems to accelerate the various
types of organic reactions.
References and notes
1. Trost, B. M. Angew. Chem., Int. Ed. Engl. 1995, 34, 259–
1H NMR (CDCl3): d 3.84 (2H, t, J = 5.8 Hz), 4.63 (2H, t,
J = 5.8 Hz), 5.23 (1H, s), 5.29 (1H, s), 7.38 (5H, m), 7.91
(1H, d, J = 8.5 Hz), 8.45 (1H, d, J = 8.5 Hz), 8.50 (1H, s).
13C NMR (CDCl3): d 37.4, 66.5, 73.5, 118.4, 119.8, 121.4,
122.6, 123.8, 124.5, 125.2, 128.1, 128.6, 130.6, 131.2,
131.5, 157.6 (2c), 159.2.
(b) 4-(2-Chloroethyl)carboxyl-N-hydroxy-phthalimide. A
mixture of compound 2 (0.30 g, 0.8 mmol) and iron chloride
(0.51 g, 3.2 mmol) in CH2Cl2 was stirred for 4 h at room
temperature. Product was extracted with ethyl acetate, and
the whole was washed with 1 N HCl, and dried over
MgSO4. The product was purified by column chromato-
graphy on silica gel (AcOEt/Hex = 1:1), giving 4-(2-chlo-
roethyl)carboxyl-N-hydroxy-phthalimide in 63% yield.
1H NMR (CDCl3): d 3.86 (2H, t, J = 5.5 Hz), 4.58 (2H, t,
J = 5.5 Hz), 7.86 (1H, d, J = 7.8 Hz), 8.32 (1H, s), 8.39 (1H,
d, J = 7.8 Hz). 13C NMR (CDCl3): d 37.0, 60.7, 118.5,
119.0, 124.8, 128.2, 130.3, 130.8, 151.5, 158.1, 159.2.
(c) 4-(2-Chloroethyl)carboxyl-N-hydroxy-phthalimide 3-
methyl-3H-imidazol-1-ium chloride 3.
281.
´
´
2. Horvath, I. T.; Rabai, J. Science 1994, 266, 72–75.
3. (a) Kitazume, T.; Nagura, H.; Koguchi, S. J. Fluorine
Chem. 2004, 125, 79–82; (b) Salaheldin, A. M.; Yi, Z.;
Kitazume, T. J. Fluorine Chem. 2004, 125, 1105–1110; (c)
Kitazume, T.; Ebata, T. J. Fluorine Chem. 2004, 125,
1509–1511; (d) Kitazume, T. In Clean Solvents; Abraham,
M. A., Moens, L., Eds.; ACS: Washington, DC, 2002; pp
50–63; (e) Kitazume, T. In Electrochemical Aspects of Ionic
Liquid; Enzymatic Reaction; Ohno, H., Ed.; John Wiley
and Sons, 2005, Chapter 10, pp 135–142, and references
cited therein.
4. (a) Kim, D. W.; Song, C. E.; Chi, D. Y. J. Am. Chem. Soc.
2002, 124, 10278–10279; (b) Kim, D. W.; Song, C. E.; Chi,
D. Y. J. Org. Chem. 2003, 68, 4281–4285; (c) Fuller, J.;
Carlin, R. T.; De Long, H. C.; Haworth, D. Chem.
Commun. 1994, 299–300, and references cited therein; (d)
Electrochemical Aspects of Ionic Liquids; Ohno, H., Ed.;
John Wiley and Sons: NJ, USA, 2005.
5. (a) Wassersheid, P.; Keim, W. Angew. Chem., Int. Ed.
2000, 39, 3773–3789; (b) Sheldon, R. Chem. Commun.
2001, 2399–2407; (c) Gordon, C. M. Appl. Catal. A,
General 2001, 222, 101–117; (d) Fraga-Dubreuil, J.;
Bazureau, J. P. Tetrahedron Lett. 2001, 42, 6097–6100;
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Hesemann, P.; Moreau, J. J. E. Chem. Commun. 2004,
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Chem. Soc. 2003, 125, 9248–9249.
7. Mi, X.; Luo, S.; Cheng, J.-P. J. Org. Chem. 2005, 70,
2338–2341.
A mixture of 4-(2-chloroethyl)carboxyl-N-hydroxy-phthal-
imide (0.36 g, 1.3 mmol) and methylimidazole (0.10 g,
1.2 mmol) in toluene (10 ml) was refluxed for 2 h, and then
the solvent was removed. The product was extracted with
water, and the aqueous layer was concentrated under
vacuum. The product was purified by column chromatog-
raphy on silica gel (CHCl3–MeOH = 1:1), giving the
compound 3 as an oil.
1H NMR (DMSO-d6): d 3.75 (3H, s), 4.03 (2H, t,
J = 6.6 Hz), 4.65 (2H, t, J = 6.6 Hz), 6.99 (1H, s), 7.15
(1H, s), 7.76 (1H, s), 8.00 (1H, d, J = 7.8 Hz), 8.29 (1H, s),
8.43 (1H, d, J = 7.8 Hz). 13C NMR (DMSO-d6): d 28.9,
38.2, 61.4, 116.5, 118.7, 119.0, 123.0, 125.6, 129.0, 130.6,
131.1, 133.5, 159.2 (2c), 159.8.
8. Handy, S. T.; Okello, M. Tetrahedron Lett. 2003, 44,
8399–8402.
(d) Compound 4.
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Lett. 2002, 1507–1509; (c) Wu, X.-E.; Ding, M.-X.; Gao,
L.-X. Synlett 2005, 607–610.
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Catal. 2004, 27, 49–66.
To the above material 3, hexafluorophosphonic acid
(1.2 mmol), and water (10 ml) were added, and the whole
was stirred for 2 h at room temperature. The layer was
washed with water, and then concentrated under vacuum,
affording the material 4 in 50%.
1H NMR (DMSO-d6): d 3.87 (3H, s), 4.02 (2H, t,
J = 5.7 Hz), 4.61 (2H, t, J = 5.7 Hz), 7.66 (1H, s), 7.68
(1H, s), 7.99 (1H, d, J = 8.0 Hz), 8.32 (1H, s), 8.38 (1H, d,
J = 8.0 Hz), 9.03 (1H, s). 13C NMR (DMSO-d6): d 31.1,
38.2, 61.1, 115.3, 118.4, 118.7, 119.1, 125.0, 128.3, 130.1,
130.9, 131.3, 152.0, 158.8, 159.5. 19F NMR (DMSO-d6): d
92.4 (d, J = 716.5 Hz) ppm from ext. C6F6.
13. Ishii, Y. J. Synth. Org. Chem., Jpn. 2003, 61, 1056–1063,
and references cited therein.
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Soc. 2000, 122, 7390–7391; (b) Isozaki, S.; Nishiwaki, Y.;
Sakaguchi, S.; Ishii, Y. Chem. Commun. 2001, 1352–1353.
General procedure for aerobic oxidation reaction.
A mixture of 1-phenyl ethanol (0.12 g, 1 mmol), IL-
supported THPI complex
4 (0.04 g, 0.1 mmol) and

S. Koguchi, T. Kitazume / Tetrahedron Letters 47 (2006) 2797–2801
2801
Co(OAc)2 (0.003 g, 0.02 mmol) in [bmim][PF6] (2 ml) was
heated at 80 °C under an atmosphere of O2. After stirring
for 5 h at that temperature, the vessel was set to 35 °C, and
then scCO2 (10 MPa at 1 ml/min) was bubbled through the
reaction mixture in ionic liquid, venting through a back-
pressure regulator in a cold trap (À78 °C). The recovered
reaction system containing IL-supported THPI complex 4,
Co(OAc)2 and [bmim][PF6] was used in the second cycle.
General procedure for nitration. A mixture of cyclohexane
(0.18 g, 1 mmol), IL-supported NHPI complex 4 (0.185 g,
0.4 mmol) and HNO3 (0.186 g, 3 mmol) in [bmim][PF6]
(6 ml) was heated at 80 °C. After stirring for 10 h at that
temperature, the organic materials were extracted with
diethyl ether, and the ethereal layer was dried over
anhydrous MgSO4. On removal of the solvent, nitro-
cyclohexane was obtained.