An efficient organic solvent-free methyltrioxorhenium-catalyzed epoxidation of alkenes with hydrogen peroxide

Article abstract of DOI:10.1016/j.tet.2008.07.033

Methyltrioxorhenium/3-methylpyrazole has proved to be an efficient catalytic system for epoxidation of alkenes with aqueous 35% H₂O₂ in excellent yields under organic solvent-free conditions. The yields of epoxides by the organic solvent-free epoxidation are comparable to those using CH₂Cl₂ as the organic solvent. The epoxidations of simple alkenes under organic solvent-free conditions are slower than those in CH₂Cl₂, while the epoxidations of alkenols such as citronellol are faster than those in CH₂Cl₂.

Full text of DOI:10.1016/j.tet.2008.07.033

Tetrahedron 64 (2008) 9253–9257
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Tetrahedron
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An efficient organic solvent-free methyltrioxorhenium-catalyzed
epoxidation of alkenes with hydrogen peroxide
*
Shigekazu Yamazaki
Toyama Industrial Technology Center, 150 Futagami, Takaoka, Toyama 933-0981, Japan
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 10 June 2008
Received in revised form 10 July 2008
Accepted 10 July 2008
Available online 16 July 2008
Methyltrioxorhenium/3-methylpyrazole has proved to be an efficient catalytic system for epoxidation of
alkenes with aqueous 35% H2O2 in excellent yields under organic solvent-free conditions. The yields of
epoxides by the organic solvent-free epoxidation are comparable to those using CH2Cl2 as the organic
solvent. The epoxidations of simple alkenes under organic solvent-free conditions are slower than those
in CH2Cl2, while the epoxidations of alkenols such as citronellol are faster than those in CH2Cl2.
Ó 2008 Elsevier Ltd. All rights reserved.
Keywords:
Methyltrioxorhenium
Hydrogen peroxide
Epoxidation
Organic solvent-free
1. Introduction
epoxides produced during the reaction. Herrmann’s group man-
aged modest increases in selectivity by addition of tertiary nitrogen
Epoxides are important compounds for both laboratory and
industry as the intermediates and the final products for a wide
range of chemicals.1,2 Although a major method for producing ep-
oxides in industry is dehydrochlorination of chlorohydrins,2 direct
epoxidation of alkenes is more favorable than the two-step
procedure,3 and extensive studies of direct epoxidation methods
have been continued.4 Various oxidants have been used for both
laboratory and industrial epoxidations. Most of the oxidants are
often hazardous and expensive, and in addition, form equimolar
amounts of the deoxygenated compounds as waste, which are
troublesome to remove from the epoxide products. The ideal alkene
epoxidation procedure must be high yield and selectivity without
any by-products through a simple and safe operation using a clean
and cheap oxidant. In this context, H2O2 is one of the ideal oxidants,
because of its high atom efficiency (47%) as oxidant and sole
theoretical side product water.5,6
Currently, methyltrioxorhenium (CH3ReO3, MTO) is one of the
most effective catalysts for epoxidation using aqueous H2O2.7 In
1991, Herrmann and co-workers reported on the H2O2 epoxidation
of various alkenes using MTO as a catalyst and t-BuOH as the sol-
vent under homogeneous reaction medium conditions.8 Although
catalytic activity of MTO has proven to be very high, the disad-
vantage of the method is acid (MTO) catalyzed hydrolysis of
bases.8,9 Since then, intense efforts have been made to improve the
performance of this significant epoxidation.10–17 Subsequently,
Sharpless and co-workers found that the addition of 12 mol %
pyridine (or substituted pyridines) under organic-aqueous biphasic
conditions using CH2Cl2 as the organic solvent both suppressed
epoxide ring-opening reaction and enhanced catalytic activity.10
Shortly afterward Herrmann reported pyrazole as a superior addi-
tive to pyridine because pyrazole is not affected under the reaction
conditions while pyridine is oxidized to pyridine N-oxide during
epoxidation.18 Recently, we reported 3-methylpyrazole as a supe-
rior additive to pyrazole because MTO/3-methylpyrazole system
has higher catalytic activity and longer catalyst lifetime than MTO/
pyrazole system.19
Generally, CH2Cl2 has been chosen as the solvent for MTO-
catalyzed epoxidation, because fast rate, high yield, and high
selectivity are obtained by using CH2Cl2.10–19 From environmental
and toxic points of view, this is certainly not the most appropriate
solvent. The negative influences of CH2Cl2 on health and the envi-
ronment20 cancel out the advantages of aqueous H2O2. The use of
environmentally friendly and lower toxic solvent instead of CH2Cl2
or organic solvent-free reaction is desirable. Although various
alternative solvents have been investigated to lower the negative
impact of CH2Cl2, only a limited success has been obtained. The
change of the solvent from CH2Cl2 to fluorinated alcohols such as
trifluoroethanol21 and hexafluoro-2-propanol22 allowed reduction
of MTO loading. However, acid-sensitive epoxides undergo ring-
opening leading to a mixture of compounds in these fluorinated
* Tel.: þ81 766 21 2121; fax: þ81 766 21 2402.
E-mail address: s-yamazk@itc.pref.toyama.jp
0040-4020/$ – see front matter Ó 2008 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2008.07.033

9254
S. Yamazaki / Tetrahedron 64 (2008) 9253–9257
alcohols.21,22 Room temperature ionic liquids were also examined
for MTO-catalyzed epoxidation. A higher MTO loading and use of
UHP (urea hydrogen peroxide adduct) were required to obtain
comparable results in ionic liquids to those in CH2Cl2.23 Very re-
cently dimethylcarbonate has been reported as the good solvent for
MTO-catalyzed oxidations.24 However, the paper reported only one
example of alkene epoxidation (styrene) using UHP as the oxidant.
Herein, we wish to report an effective organic solvent-free
epoxidation of alkenes with aqueous 35% H2O2 catalyzed by MTO
using 3-methylpyrazole as an additive when alkenes are liquid. This
reaction will be performed under entirely organic solvent-free and
halide-free conditions, and avoids the solvent problem.
an important role as phase-transfer catalyst,10d transporting the
peroxo complexes of MTO from the aqueous layer into CH2Cl2.
Because of the poor solubility of pyrazole in cyclohexene, pyrazole
does not work as good phase-transfer catalyst in the cyclohexene-
aqueous H2O2 biphasic system. This must be the reason of the
unsatisfactory result using pyrazole.
When the organic solvent-free epoxidations of cyclohexene
were carried out with 3-methylpyrazole, compared with un-
satisfactory results using pyridine and pyrazole, a good result was
obtained. The reaction completed within 3 h to give 97% yield of
cyclohexene oxide (entry 7). Because of the good solubility in
cyclohexene, 3-methylpyrazole works as good phase-transfer
catalyst in the cyclohexene-aqueous H2O2 biphasic system. And
furthermore, the lower basicity of 3-methylpyrazole (pKa¼3.3)
than pyridine (pKa¼5.2) must prevent the decomposition of
MTO.10d These must be the reasons of the excellent result of
3-methylpyrazole as the additive.
The results in Table 1 clearly indicated that 3-methylpyrazole is
an effective additive for organic solvent-free epoxidation of alkenes
catalyzed by MTO with aqueous H2O2 as the terminal oxidant, and
that pyridine and pyrazole are ineffective for this purpose.
We then investigated the influence of the amount of 3-meth-
ylpyrazole added on the cyclohexene epoxidation under organic
solvent-free conditions. As can be seen from Figure 1, the efficient
epoxidation required 10 mol % or higher amount of 3-methylpyr-
azole.28 For comparison and general applicability, the amount of
3-methylpyrazole (10 mol %) was maintained for all experiments.
MTO-catalyzed epoxidations of a variety of alkenes using
3-methylpyrazole as an additive under organic solvent-free con-
ditions were examined. The results are summarized in Table 2.
Cyclic alkenes, 1-methylcyclohexene, 1-phenylcyclohexene,
cyclopentene, cycloheptene, and cyclooctene, required longer re-
action time compared to the reaction in CH2Cl2 with comparable
conversions and yields of epoxides (entries 1–10).
2. Results and discussion
We first examined organic solvent-free MTO-catalyzed epoxi-
dation of cyclohexene using pyridine,10 pyrazole,18 and 3-methyl-
pyrazole19 as the additives (Table 1). These three additives have
been reported to be effective for MTO-catalyzed cyclohexene ep-
oxidation under CH2Cl2-aqueous biphasic conditions. Pyridine and
3-methylpyrazole are liquid at room temperature and soluble in
cyclohexene. On the other hand, pyrazole is solid at room
temperature and insoluble in cyclohexene.
The reaction without additive or organic solvent resulted in
hydrolysis of the epoxide produced, and only a trace amount of the
epoxide was detected (entry 1).
The epoxidation of cyclohexene with 0.2 mol % MTO in the
presence of 10 mol % pyridine, pyrazole, or 3-methylpyrazole in
CH2Cl2 gave quantitative conversion to cyclohexene oxide (entries
2, 4, and 6).19
When the epoxidation of cyclohexene was carried out without
organic solvent in the presence of pyridine, the reaction stopped
within 30 min with large amount of unreacted cyclohexene
remained (entry 3). The yellow color of the reaction mixture, which
indicates the presence of catalytically active peroxo rhenium
species,8 changed to colorless within 30 min. This indicated that
the decomposition of MTO is rapid in the presence of pyridine
under organic solvent-free conditions.13c,25–27
MTO-catalyzed epoxidation of 1-octene, aliphatic terminal
alkene, was slower under organic solvent-free conditions than that
100
80
60
40
20
0
Although pyrazole is not dissolved in common alkenes, aqueous
H2O2 dissolves pyrazole. When the epoxidations of cyclohexene
were carried out without organic solvent in the presence of pyr-
azole (dissolved in aqueous H2O2 before mixing with cyclohexene
and MTO), the reaction stopped within 1 h with low conversion of
the alkene and low yield of epoxide (entry 5). It is reported that in
CH2Cl2-aqueous H2O2 biphasic system the additive (pyridine) play
Table 1
a
MTO-catalyzed epoxidation of cyclohexene with 35% H2O2
35% H2O2 / 0.2 mol% MTO
10 mol% additive
O
rt
Entry Additive
Solventb Time (h) Conversionc (%) Epoxidec,d (%)
1
2
3
4
5
6
7
de
df
5
5
0.5
3
1
89
99
14
>99
25
>99
>99
<1
>99
14
>99
14
Pyridine
Pyridine
Pyrazole
Pyrazole
CH2Cl2
df
CH2Cl2
df
3-Methylpyrazole CH2Cl2
1
3
>99
97
0
1
2
3
Time / h
4
5
6
3-Methylpyrazole df
a
Cyclohexene (20 mmol), 35% H2O2 (40 mmol), additive (2 mmol), MTO
(0.04 mmol) at room temperature in CH2Cl2 (10 mL) or without organic solvent.
Figure 1. Time course of MTO-catalyzed epoxidation of cyclohexene with different
amounts of 3-methylpyrazole under organic solvent-free conditions. Conditions:
cyclohexene (10 mmol), 35% H2O2 (20 mmol), MTO (0.02 mmol), and 3-methylpyrazole
at 20 ꢀC. Analysis by GC: (C) Curve A: 1.5 mmol (15 mol %) 3-methylpyrazole. (:)
Curve B: 1.0 mmol (10 mol %) 3-methylpyrazole. (,) Curve C: 0.5 mmol (5 mol %) 3-
methylpyrazole. The curve of 20 mol % 3-methylpyrazole lapped over that of 15 mol %.
b
The results of epoxidation in CH2Cl2 are from Ref. 19.
Determined by GC analysis.
Yield of cyclohexene oxide based on cyclohexene used.
Reaction without additive.
c
d
e
f
Reaction without organic solvent.

S. Yamazaki / Tetrahedron 64 (2008) 9253–9257
9255
Table 2
MTO-catalyzed epoxidation of various alkenes with 35% H2O2 in the presence of 3-methylpyrazolea,b
Entry
Alkene
Solvent
MTO (mol %)
Temperature (ꢀC)
Time (h)
Conversionc (%)
Epoxidec (%)
1
2
0.1
0.1
10
10
5
9
>99
>99
>99
>99
CH2Cl2
dd
3
4
0.1
0.1
rt
3
9
>99
>99
95
85
CH2Cl2
dd
10
5
6
0.1
0.1
rt
2.5
6
>99
>99
>99
>99
CH2Cl2
dd
10
7
8
0.1
0.1
rt
rt
3
7
>99
>99
>99
CH2Cl2
dd
89
9
0.1
0.1
rt
rt
2
3
>99
>99
>99
>99
CH2Cl2
10
dd
11
12
0.5
0.5
rt
rt
8
8
98
74
91
62
CH2Cl2
dd
13
14
0.1
0.1
rt
rt
5
>99
>99e
85e
CH2Cl2
dd
24
96
15
16
0.1
0.1
rt
rt
3
8
>99
>99
>99f
90f
CH2Cl2
dd
17
18
19
0.5
0.5
0.5
rt
4
>99
82
>99
97g
43h
98i
CH2Cl2
dd
dd
rt
10
0.5
2.5
20
21
0.1
0.1
rt
3
5
>99
>99
92
97
CH2Cl2
dd
10
22
23
0.1
0.1
rt
5
5
>99
>99
>99e
>99e
CH2Cl2
dd
10
24
25
0.1
0.1
rt
5
7
>99
>99
>99f
>99f
CH2Cl2
dd
10
26
27
28
0.1
10
10
10
4
2
4
>99
>99
>99
97
>99
95
CH2Cl2
dd
0.1
0.04
OH
OH
dd
29
30
0.2
0.2
rt
8
8
>99
>99
>99e
>99e
CH2Cl2
dd
10
31
32
a
0.2
0.2
rt
6
2
>99
>99
99e
95e
CH2Cl2
OH
dd
10
Alkene (20 mmol), 35% H2O2 (40 mmol), 3-methylpyrazole (2 mmol), in CH2Cl2 (10 mL) or without organic solvent.
The results of epoxidation in CH2Cl2 are from Ref. 19.
Yields of epoxides based on alkenes used. Determined by GC analysis.
Reaction without organic solvent.
b
c
d
e
f
trans-Epoxide.
cis-Epoxide.
g
h
i
Styrene glycol (2%) and benzaldehyde (1%) were also produced.
Styrene glycol (24%) and benzaldehyde (5%).
Only trace amounts of styrene glycol and benzaldehyde were detected.
in CH2Cl2 (entries 11 and 12). The internal alkenes such as trans-
and cis-2-octene were also converted to the corresponding epox-
ides under organic solvent-free conditions in somewhat lower yield
of epoxides at longer reaction times compared to the epoxidation in
CH2Cl2 (entries 13–16).
glycol 50%, and benzaldehyde 9%). A marked improvement
was observed when the reaction was performed at 10 ꢀC. The re-
action was faster than that in CH2Cl2 at room temperature, and
complete conversion and excellent yield of the epoxide were
obtained (entry 19).
Styrene oxide is known to be very prone to ring-opening
reaction. Although MTO-catalyzed epoxidation of styrene in CH2Cl2
afforded excellent yield of the epoxide (entry 17), the same epox-
idation without organic solvent at room temperature resulted in
the formation of large amount of styrene glycol (24%) and benzal-
dehyde (5%) with lower amount of epoxide (43%) in 82% conversion
at 30 min (entry 18). The longer reaction time caused hydrolysis of
the epoxide (after 2.5 h, conversion 95%, styrene oxide 5%, styrene
Organic solvent-free MTO-catalyzed epoxidation of
a
-methyl-
styrene, cis- and trans-
b
-methylstyrene proceeded smoothly at
10 ꢀC to give the corresponding epoxides in excellent yields within
comparable reaction times to the reaction in CH2Cl2 at room
temperature (entries 20–25).
Citronellol was converted to the corresponding epoxide in
excellent yield with 0.1 mol % MTO within 2 h at 10 ꢀC. The reaction
is faster than that in CH2Cl2 (entries 26 and 27). A complete

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S. Yamazaki / Tetrahedron 64 (2008) 9253–9257
conversion of citronellol to the corresponding epoxide quantita-
tively was also observed with reduced amount of MTO (0.04 mol %)
with prolonged reaction time (entry 28). A scale-up epoxidation of
citronellol (20 g) was examined. The epoxidation and work-up
were carried out under entirely CH2Cl2 and any chlorine containing
compounds free conditions, and 16.7 g (76%) of corresponding
epoxide was isolated (see detail Section 4).
phase. The conversion of cyclohexene and yield of cyclohexene
oxide were determined by GC internal standard method. The GC
internal standard material (n-undecane) was added just before the
first analysis.
4.2. Procedure for 20 g scale epoxidation of citronellol
Homoallylic alcohol, trans-3-hexen-1-ol, and allylic alcohol,
trans-2-hexene-1-ol were also converted to the corresponding
epoxides in excellent yields (entries 30 and 32). The rate of epox-
idation of trans-3-hexen-1-ol under organic solvent-free condition
at 10 ꢀC is faster than that in CH2Cl2 at room temperature. The rate
of epoxidation of trans-2-hexene-1-ol was slower than those of
trans-3-hexen-1-ol and citronellol.
As shown above, the epoxidation of simple cyclic alkenes and
aliphatic alkenes under organic solvent-free conditions is generally
slower than that in CH2Cl2. This is because the solubility of the
catalytically active peroxo rhenium complexes is lower in those
alkenes compared to in CH2Cl2 solution. On the other hand, the
results that the epoxidation of styrenes and alkenols is faster than
in CH2Cl2 indicated that the peroxo complexes are dissolved in
these alkenes at high concentrations. In every alkene, the yields of
epoxides by MTO-catalyzed epoxidations using 3-methylpyrazole
under organic solvent-free conditions are comparable with those
obtained by epoxidation in CH2Cl2.
A 200-mL flask equipped with a stirbar was charged with cit-
ronellol (20 g, 128 mmol), 3-methylpyrazole (1.03 mL, 12.8 mmol,
10 mol %), and MTO (31.9 mg, 0.128 mmol, 0.1 mol %). The flask was
cooled to 10 ꢀC by applying an external cooling bath. H2O2 (35%,
21.5 mL, 256 mmol) was added dropwise to the stirring solution
from dropping funnel (ca. 50 min). During the H2O2 addition the
temperature of the solution was kept below 22 ꢀC. The resulted
two-phase mixture was stirred vigorously (1000 rpm) at 10 ꢀC. The
reaction was completed after 2 h. AcOEt was added to the reaction
mixture, and the mixture was washed successively with aqueous
solution of Na2SO4 (two times) and with aqueous solution of
Na2S2O3. Then the organic layer was washed with aqueous solution
of tartaric acid (5 g in 50 mL H2O) to remove 3-methylpyrazole,
followed with aqueous solution of NaHCO3. The organic layer was
dried over anhydrous Na2SO4, and AcOEt was distilled out by
evaporator. The residual oil was dried under vacuum to give crude
citronellol oxide (18.5 g). Vacuum distillation (1 Torr, 122–123 ꢀC)
afforded citronellol oxide as colorless oil (16.7 g, 76%, >96% purity
by GC). The physical data agreed with that previously reported.31
Although various catalytic epoxidations with aqueous H2O2
under organic solvent-free conditions have been reported, most of
them are tungstate-based catalysts.29 The method described in this
paper is superior to previously reported methods in terms of low
catalyst loading and high epoxide selectivity. The outstanding
advantage is the excellent yields of acid-sensitive epoxides such as
styrene oxide.29b,c
References and notes
1. Yudin, A. K. Aziridines and Epoxides in Organic Synthesis; Wiley-VCH: Weinheim,
2006.
2. Weissermel, K.; Arpe, H.-J. Industrial Organic Chemistry, Fourth, Completely
Reviced Edition; Wiley-VCH: Weinheim, 2003.
3. Sheldon, R. A. Green Chem. 2007, 9, 1273.
3. Conclusions
4. (a) Sheldon, R. A.; Kochi, J. K. Metal-Catalyzed Oxidations of Organic Compounds;
Academic: New York, NY, 1981; (b) Adam, W. Peroxide Chemistry; Wiley-VCH:
Weinheim, 2000; (c) Ba¨ckvall, J.-E. Modern Oxidation Methods; Wiley-VCH:
Weinheim, 2004.
5. (a) Strukul, G. Catalytic Oxidations with Hydrogen Peroxide as Oxidant; Kluwer
Academic: New York, NY, 1992; (b) Jones, C. W. Application of Hydrogen Peroxide
and Derivatives; Royal Society of Chemistry: Cambridge, 1999.
6. Reviews on epoxidation using H2O2 as an oxidant. (a) Grigoropoulou, G.; Clark,
J. H.; Elings, J. A. Green Chem. 2003, 5, 1; (b) Noyori, R.; Aoki, M.; Sato, K. Chem.
Commun. 2003, 1977; (c) Lane, B. S.; Burgess, K. Chem. Rev. 2003, 103, 2457; (d)
Mizuno, N.; Yamaguchi, K. Chem. Rec. 2006, 6, 12.
7. Reviews on MTO-catalyzed oxidations. (a) Espenson, J. H. Chem. Commun. 1999,
479; (b) Owens, G. S.; Arias, J.; Abu-Omar, M. M. Catal. Today 2000, 55, 317; (c)
Ku¨hn, F. E.; Scherbaum, A.; Herrmann, W. A. J. Organomet. Chem. 2004, 689,
4149; (d) Adolfsson, H. Ref. 4c, pp 21–49; (e) Adolfsson, H.; Balan, D. Ref. 1, pp
185–228.
We have explored and succeeded for the first time in performing
MTO-catalyzed epoxidation with aqueous 35% H2O2 under organic
solvent-free conditions using 3-methylpyrazole as an additive. The
use of 3-methylpyrazole is significant for achieving high epoxides’
yields. Pyridine and pyrazole were inferior to 3-methylpyrazole as
the additive for organic solvent-free epoxidation. This method will
exclude CH2Cl2 and any chlorine containing compounds from the
reaction system, and will avoid negative impact of CH2Cl2.
4. Experimental
8. (a) Herrmann, W. A.; Fischer, R. W.; Marz, D. W. Angew. Chem., Int. Ed. Engl. 1991,
30, 1638; (b) Herrmann, W. A.; Fischer, R. W.; Scherer, W.; Rauch, M. U. Angew.
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119, 6189; (b) Cope´ret, C.; Adolfsson, H.; Sharpless, K. B. Chem. Commun. 1997,
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All reagents obtained were from commercial sources unless
otherwise noted and were used without further purification.
Methyltrioxorhenium was prepared according to the reported
procedure.30 The concentration of hydrogen peroxide was de-
termined by iodometric titration before use. The progress of the
reaction was monitored by GC analysis. The conversion of alkenes
and yield of epoxides were determined by GC internal standard
method. GC analyses were performed on Shimadzu GC-2010 (FID
detector) equipped with GL Sciences InertCap 1 column (30 m
11. (a) Yudin, A. K.; Sharpless, K. B. J. Am. Chem. Soc. 1997, 119, 11536; (b) Yudin,
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A. K.; Chiang, J. P.; Adolfsson, H.; Coperet, C. J. Org. Chem. 2001, 66, 4713.
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lengthꢁ0.25 mm IDꢁ0.25
mm film thickness).
´
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4.1. Cyclohexene epoxidation (Table 1, entry 7)
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Ajlouni, A. M.; Espenson, J. H. J. Org. Chem. 1996, 61, 3969; (c) Wang, W. D.;
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A 50-mL flask equipped with a stirbar was charged with cyclo-
hexene (2.03 mL, 20 mmol), 3-methylpyrazole (161 mL, 2.0 mmol,
10 mol %), and MTO (10 mg, 0.020 mmol, 0.1 mol %). H2O2 (35%,
3.36 mL, 40 mmol) was added all at once to the stirring solution.
The resulted two-phase mixture was stirred vigorously (1000 rpm)
at room temperature. The progress of the reaction was monitored at
appropriate interval by GC analysis of small aliquots of the organic

S. Yamazaki / Tetrahedron 64 (2008) 9253–9257
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