Unique salt effect on highly selective synthesis of acid-labile terpene and styrene oxides with a tungsten/Hcatalytic system under acidic aqueous conditions

Article abstract of DOI:10.1055/s-0031-1290948

Acid-labile epoxides such as terpene and styrene oxides are effectively synthesized in high yields with good selectivities using tungsten-catalyzed hydrogen peroxide epoxidation in the presence of NaO The salt effect is thought to originate with the addition of a saturated amount of NaOto aqueous H this addition strongly inhibited the undesired hydrolysis of the acid-labile epoxy products, despite the biphasic conditions of substrate as oil phase and Has acidic aqueous phase.

Full text of DOI:10.1055/s-0031-1290948

1672▌
PAPER
paper
Unique Salt Effect on Highly Selective Synthesis of Acid-Labile Terpene and
Styrene Oxides with a Tungsten/H2O2 Catalytic System under Acidic Aqueous
Conditions
Houjin Hachiya,a Yoshihiro Kon,*a Yutaka Ono,a Kiyoshi Takumi,b Naoki Sasagawa,b Yoichiro Ezaki,b Kazuhiko Sato*a
a
National Institute of Advanced Industrial Science and Technology (AIST), Central 5 Higashi 1-1-1, Tsukuba, Ibaraki, 305-8565, Japan
Fax +81(29)8614670; E-mail: y-kon@aist.go.jp
b
Arakawa Chemical Industries, Ltd., 5, Okubo, Tsukuba, Ibaraki, 300-2611, Japan
Received: 13.02.2012; Accepted after revision: 14.03.2012
mediates and/or precursors for chemical production,
Abstract: Acid-labile epoxides such as terpene and styrene oxides
including resins, paints, glues, flavors, and pharmaceuti-
are effectively synthesized in high yields with good selectivities us-
cals.8 Although various types of aqueous H2O2 epoxida-
ing tungsten-catalyzed hydrogen peroxide epoxidation in the pres-
ence of Na2SO4. The salt effect is thought to originate with the
tion of terpenes and styrenes have been reported,9–13 their
addition of a saturated amount of Na2SO4 to aqueous H2O2; this ad- reaction is still a challenging task due to their sensitivity
toward H2O2 acidic media.8 For example, the isomeriza-
tion of α-pinene in the presence of acid catalysts with
acidic media has been widely studied, and it produces a
complex mixture of mono- and bicyclic terpenes such as
dition strongly inhibited the undesired hydrolysis of the acid-labile
epoxy products, despite the biphasic conditions of substrate as oil
phase and H2O2 as acidic aqueous phase.
Key words: oxidation, catalysis, epoxides, terpenoids, green chem-
istry
β-pinene, limonene, camphene, 3-carene, terpineol, and
so on.8 And through the H2O2 epoxidation of α-pinene,
isomerization and/or hydrolysis of the product also lead to
The epoxidation of olefins is a fundamental process for
the laboratory and for industrial manufacturing because
epoxy compounds include a wide variety of useful chem-
icals.1 While various oxidants are now being used for ep-
oxidation,2 they often give equimolar amounts of the
deoxygenated compounds as waste that no longer meets
current environmental constraints.
a complex mixture of terpenoids (campholenic aldehyde,
pinanediol, sobrerol, etc.) as shown in Scheme 1.8,14
O
H2O2 epoxidation
acidic conditions
Hydrogen peroxide (H2O2) is an ideal oxidant because
water is the only side product,3 its atom efficiency4 is ex-
cellent, and it is cheap, readily available, and easy to han-
dle. Although a number of metal-catalyzed H2O2
epoxidation reactions have been reported thus far,5,6 the
chemical processes using organic solvent and halide com-
pounds should be converted to organic solvent- and ha-
lide-free processes from both an industrial perspective,
taking costs into account, and an environmental perspec-
tive. In this context, we have developed various epoxida-
tion reactions of olefins, including terminal aliphatic
olefins with aqueous H2O2 under halide- and organic-sol-
vent-free conditions.7 This oxidation process gives the
corresponding epoxides in good yields catalyzed by high-
ly active tungsten peroxide species that are effectively
formed at 90 °C under acidic conditions.7b
OH
OH
OH
O
OH
Scheme 1 Isomerization and/or hydrolysis of α-pinene oxide
A few successful examples utilizing an immobilized cata-
lyst of polyoxometalates on mesoporous silica gel and
methyltrioxorhenium catalysts have been shown to effec-
tively catalyze α-pinene epoxidation.15,16 However, these
methods are not fully satisfactory for practical syntheses
because of the requirement of hazardous organic solvents,
more than equimolar amounts of H2O2, and/or the compli-
cated multistep preparation of catalysts using organic sol-
vents. Therefore, a catalytic system applicable to the
avoidance of the decomposition of acid-labile terpene and
styrene oxides was employed under organic solvent-free
conditions. Recently, the epoxidation of terpene and sty-
rene under weak acidic conditions in which the pH was
adjusted by adding NaOH was also employed.17 It was
also revealed that the combination of Na2WO4, [Me(n-
C8H17)3N]HSO4, PhP(O)(OH)2, and NaOH was effective
for the epoxidation of terpene and styrene at 25–35 °C.
However, acid-labile terpene and styrene oxides were not
obtained under these reaction conditions because the gen-
erated epoxides easily underwent ring opening, rearrange-
ment, and hydrolysis by acid catalysis or by the
application of heating.8 Terpene and styrene oxides are
key raw materials; they are some of the most useful inter-
SYNTHESIS 2012, 44, 1672–1678
Advanced online publication: 26.04.2012
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DOI: 10.1055/s-0031-1290948; Art ID: SS-2012-F0145-OP
© Georg Thieme Verlag Stuttgart · New York

PAPER
H2O2 Epoxidation of Terpenes and Styrenes
1673
But this process required as much as 0.08 equivalent of the produced epoxide 2 decomposed under acidic condi-
catalysts and 1.3 equivalents of intractable 60% H2O2 for tions (55% conversion of 1 and 1% yield of 2). The addi-
the reaction to proceed. Based on these results, we have tion of 0.6 equivalent of NaHCO3 to the aqueous phase
developed another synthetic approach that effectively created an alkaline solution (pH 9.0), and as a result the
protects the generated acid-labile terpene and styrene ox- H2O2 epoxidation did not proceed (Table 1, entry 2). The
ides from hydrolysis under organic solvent-free acidic addition of 0.6 equivalent of NaCl to the epoxidation re-
conditions, maintaining the intrinsic catalyst reactivity at action afforded only 20% conversion of 1 and 15% yield
the same time.14 We report here the effective and conve- of 2 (Table 1, entry 3). The addition of 0.6 equivalent of
nient tungsten-catalyzed H2O2 epoxidation of terpenes NaNO3 did not give 2 at all (Table 1, entry 4). One of the
and styrenes by the simple addition of inorganic neutral reasons for the low conversion of 1 in Table 1, entries 1–
salts to give the acid-labile epoxides in good to excellent 4, is that sobrerol (3) formed by the hydrolysis of 2 might
yields. This process required as much as 0.02 equivalent be chelated with tungstate metal at the diol moiety of 3,18
of tungsten, 0.02 equivalent of phase-transfer catalyst, which would prohibit any possibility of the epoxidation
0.01 equivalent of phenyl phosphonic acid or phosphoric proceeding. It is noteworthy that the Na2WO4, [Me(n-
acid, and 1.0 equivalent of commercially available 30% C8H17)3N]HSO4, and PhP(O)(OH)2 catalyzed H2O2 epox-
H2O2 aqueous solution for the reaction to proceed under idation of 1 with 0.3 equivalent of Na2SO4 as divalent neu-
organic solvent-free biphasic conditions of substrate as tral salts, exhibits excellent efficiency despite the acidic
the oil phase and aqueous H2O2 as the acidic water phase. conditions (pH 2.0) and produced 2 in 89% yield and
100% selectivity (Table 1, entry 5). The catalytic H2O2 ep-
The H2O2 epoxidation of α-pinene (1) was examined as
oxidation of 1 with sulfates of other cation species such as
the screening substrate, because 1 is not only a major
+
Li+, NH4 , and Mg2+ proceeded moderately to give 40%,
component of gum turpentine but also a challenging ter-
pene that is difficult to inhibit the hydrolysis during the re-
action. The reaction was conducted with 30% H2O2 (1.0
equiv to 1), Na2WO4 (tungsten catalyst, 0.02 equiv),
44%, and 30% yields of 2 with selectivity of 55%, 60%,
and 43%, respectively (each 0.3 equivalent, Table 1, en-
tries 6, 8, and 9). In contrast, the reaction in the presence
of 0.3 equivalent of K2SO4 afforded 2 in only 6% yield
[Me(n-C8H17)3N]HSO4 (phase-transfer catalyst, 0.02
(Table 1, entry 7). The addition of 0.3 equivalents of
equiv) at 25 °C for 16 hours with vigorous stirring. As
Na2SO410H2O to the epoxidation reaction afforded 69%
shown in Table 1, entry 1, the epoxidation reaction in the
absence of any additional salts proceeded moderately, but
conversion of 1 and 23% yield of 2 (Table 1, entry 10).
Table 1 Effects of Salts on Tungsten-Catalyzed H2O2 Epoxidation of 1 under Acidic Conditionsa
30% H2O2 (1.0 equiv)
Na2WO4 (0.02 equiv)
[Me(n-C8H17)3N]HSO4 (0.02 equiv)
PhP(O)(OH)2 (0.01 equiv)
O
salt
25 °C, 16 h
1
2
Conversion (%)b
Yield (%)b
Selectivity (%)c
Entry
Salt (equiv)
1
2
none (0)
55
3
1
0
2
0
NaHCO3 (0.6)
NaCl (0.6)
3
20
31
89
73
57
74
69
69
15
0
75
0
4
NaNO3 (0.6)
Na2SO4 (0.3)
Li2SO4 (0.3)
K2SO4 (0.3)
5
89
40
6
100
55
11
60
43
33
6
7
8
(NH4)2SO4 (0.3)
MgSO4 (0.3)
Na2SO410H2O (0.3)
44
30
23
9
10
a Reaction conditions: 1 (1.0 equiv), 30% H2O2 (1.0 equiv), Na2WO4 (0.02 equiv), [Me(n-C8H17)3N]HSO4 (0.02 equiv), PhP(O)(OH)2 (0.01
equiv), salt, 25 °C, 1000 rpm, 16 h.
b Determined by GC analysis with n-decane as an internal standard.
c Yield/conversion (%).
© Georg Thieme Verlag Stuttgart · New York
Synthesis 2012, 44, 1672–1678

1674
H. Hachiya et al.
PAPER
To clarify the effect of the addition of salt on H2O2 epox- Na2SO4, and the reaction in the absence of Na2SO4
idation, a simple hydrolysis reaction of 2 was carried out showed low yield (Table 3, entries 1 and 2).The reaction
with aqueous 30% H2O2 (1.0 equiv to 2) in the presence of with α-terpineol and terpinen-4-ol having a hydroxy
Na2SO4 (0.3 equiv) without any other catalysts at 25 °C group that causes intramolecular addition reactions in its
for 16 hours (Table 2). As a result, the hydrolysis of 2 was product under acidic conditions19 also gave the corre-
only 5% with 0.3 equivalent of Na2SO4 when the biphasic sponding epoxides in good to high yield (67% and 82%,
mixture of 2 was stirred with 30% H2O2 (Table 2, entry 4). respectively, Table 3, entries 3 and 4). A reaction with
On the other hand, the hydrolysis of 2 occurred complete- isopulegol gave the corresponding epoxides in excellent
ly in the absence of Na2SO4, and the hydrolysis of 2 to yield (97%, Table 3, entry 5). The hydroxy group in allyl-
give 3 was observed in 62% yield as main product (Table ic alcohols has been known to facilitate the epoxida-
2, entry 1). The amount of the added salts is also crucial to tion.7b,c The hydroxy group at homoallylic position in
effectively protect the generated epoxides from hydroly- isopulegol might also facilitate the epoxidation. The epox-
sis. Table 2 shows the results of the investigation regard- idation of limonene, which has two alkene moieties in the
ing the relationship between the conversion of 2 and the molecule, also successfully produced the corresponding
amount of Na2SO4 in the biphasic reaction. The amount of monoepoxides in high yield (89%, Table 3, entry 6).
Na2SO4 increased from 0 to 0.4 equivalent, and the de-
composition rate of 2 decreased from 100% to 4% (Table Table 3 Tungsten-Catalyzed H2O2 Epoxidation of Terpenes under
a
Acidic Conditions Using Na2SO4
2, entries 1 and 5). These results suggest that the addition
of Na2SO4 clearly enhanced the inhibition of the hydroly-
Entry Alkene
Product
Conversion Yield
sis of 2. But in comparing entries 4 and 5, the addition of
more than 0.3 equivalent of Na2SO4 seems less effective
because the aqueous H2O2 solution was saturated by the
addition of 0.3 equivalent of Na2SO4. The results clearly
showed that the addition of a saturated amount of Na2SO4
effectively inhibited the hydrolysis of 2 under the H2O2
epoxidation reaction conditions at room temperature
without deactivation of the tungsten peroxide species.
(%)b
(%)b
O
1
2c
89
55
89
1
O
67 d
3
77
100
97
Table 2 Effects of Na2SO4 on the Inhibition of Hydrolysis of 2 in the
Presence of 30% H2O2
a
OH
OH
O
OH
O
30% H2O2 (1.0 equiv)
with or without
Na2SO4 (0 to 0.4 equiv)
4
5
6
7
82
OH
25 °C, 16 h
OH
OH
2
3
Entry
Na2SO4
(equiv)
Decomposition of 2 Yield of 3
(%)b
(%)b
97
OH
OH
1
2
3
4
5
0
100
59
11
5
62
22
11
5
O
O
0.1
0.2
0.3
0.4
91
89
4
4
a Reaction conditions: 2 (1.0 equiv), 30% H2O2 (1.0 equiv), Na2SO4,
25 °C, 1000 rpm, 16 h.
O
O
O
O
b Determined by GC analysis with n-decane as an internal standard.
50
(41:9)
51
O
This epoxidation reaction using Na2SO4 as an additive un-
der the biphasic conditions can be adopted for various ter-
penes to generate the corresponding terpene oxides. And
the concentration of H2O2 in the solution was 30% regard-
less of the presence or absence of Na2SO4. These results
are summarized in Table 3. As previously shown in Table
1, entries 1 and 5, tungsten-catalyzed H2O2 epoxidation
reaction of 1 proceeded in good yield in the presence of
a Reaction conditions: terpenes (1.0 equiv), 30% H2O2 (1.0 equiv),
Na2WO4 (0.02 equiv), [Me(n-C8H17)3N]HSO4 (0.02 equiv),
PhP(O)(OH)2 (0.01 equiv), Na2SO4 (0.3 equiv), 25 °C, 1000 rpm, 16
h.
b Determined by GC analysis with n-decane or biphenyl as an internal
standard.
c The reaction was run in the absence of Na2SO4.
d Ratio cis/trans = 1:1.
Synthesis 2012, 44, 1672–1678
© Georg Thieme Verlag Stuttgart · New York

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H2O2 Epoxidation of Terpenes and Styrenes
1675
Meanwhile, it should be noted that the addition of a cata-
Table 4 Tungsten-Catalyzed H2O2 Epoxidation of Styrenes under
a
lytic amount of Na2SO4 for H2O2 epoxidation of limonene Acidic Conditions Using Na2SO4
has already been reported,20 while the reaction required an
Entry Alkene
Product
Conversion Yield
organic solvent. In this reaction, three alkyl substituted
cyclic alkene moiety was epoxidized preferentially.7b The
epoxidation of carvone, which has a carbonyl group and
two alkenes, also gave two types of mono epoxides in a to-
tal 50% yield with a specific rate. Carvone 7,8-oxide was
obtained in 41% yield, and carvone 1,6-oxide was formed
in 9% yield (Table 3, entry 7). The cyclic alkene in car-
vone is in conjugation with the carbonyl group. In the case
of tungsten-catalyzed epoxidation, the stabilization by the
conjugation might be one reason for the low reactivity of
carvone.7b,c
(%)b
(%)b
O
1
2c
3e
85
83d
0
87
91
57
O
4
82
88
86
96
75
79
83
96
F
F
O
5
This catalytic system using Na2SO4 as an additive under
the acidic aqueous biphasic conditions was also applied to
the syntheses of various styrene oxides that are easily hy-
drolyzed under acidic conditions. Generally, a reaction
with styrene gives the corresponding styrene oxides,21
which easily undergo rearrangement, overoxidation, and
hydrolysis to give 1-phenylethane-1,2-diol, benzalde-
hyde, benzoic acid, etc., with aqueous H2O2.13 As shown
in Table 4, entry 1, epoxidation of styrene effectively gave
styrene oxide in 85% yield and 98% selectivity, while the
reaction without Na2SO4 did not give styrene oxide at all
(Table 4, entry 3). Epoxidation of electron-deficient sty-
renes such as p-fluoro-, p-chloro-, and p-bromostyrene
gave the corresponding oxides in moderate to good yields
(75%, 79%, and 83%, Table 4, entries 4, 5, and 6, respec-
tively). Epoxidation of α-methylstyrene gave its oxide in
high yield (96%, Table 4, entry 7). A reaction with trans-
β-methylstyrene and cis-β-methylstyrene gave the corre-
sponding oxides in moderate to high yields (55% and
89%, Table 4, entry 8 and 9, respectively). The high reac-
tivity of cis-β-methylstyrene relative to the trans-β-meth-
ylstyrene could be explained by the steric hindrance of the
substituent of olefin with a peroxotungsten complex in the
Cl
Cl
Br
O
6
Br
O
7
O
O
8
9
55
89
55
89
a Reaction conditions: styrenes (1.0 equiv), 30% H2O2 (1.0 equiv),
Na2WO4 (0.02 equiv), [Me(n-C8H17)3N]HSO4 (0.02 equiv), H3PO4
(0.01 equiv), Na2SO4 (0.3 equiv), 25 °C, 1000 rpm, 16 h.
b Determined by GC analysis with n-decane or biphenyl as an internal
standard.
c Synthesis scale: 1 gram.
d Isolated yield, epoxide (mol)/styrene (mol) × 100 (%).
spiro-structured model in the transition state.7c The pres- e The reaction was run in the absence of Na2SO4.
ent method can be carried out on gram-scale synthesis of
acid-labile epoxides. That is, with 1.06 grams of styrene
+
NH4 with sulfate anion SO42–, Na+ is the most effective
as the starting material, 1.01 grams of the corresponding
epoxides was obtained after column chromatography on
silica gel using ethyl acetate as an eluent (83% yield, Ta-
ble 4, entry 2). However, the epoxidation of various sub-
strates is often quite exothermic. Although the reaction
proceeded in the presence of Na2SO4, careful reaction
temperature control was found to be crucial to a large-
scale preparation.
salt for the salting-out process under biphasic conditions
using various solvents as the oil phase and aqueous solu-
tion as the water phase.25 On the other hand, nitrate anion
–
NO3 is known to have the smallest salting-out effect; this
is one reason why the epoxidation reaction of 1 using
NaNO3 did not give 2 at all (Table 1, entry 4). However,
the findings regarding hydrolysis inhibition in the bipha-
sic epoxidation reaction cannot simply explain the reac-
tivity due to the interaction between substrate 2 and
cations, or to the interaction between the catalyst species
and anions.
Recently, specific salt effects on the structure of water
have been the subject of increasing attention.22 Under the
biphasic conditions of benzene (oil phase) and aqueous
solution (water phase), the solubility of benzene to the wa-
ter phase was effectively reduced by Na2SO4.23 The great-
er abilities of sulfate anion (SO42–) and sodium cation
(Na+) compared with other anions and cations, respective-
ly, to decrease protein solubility in aqueous solution is
known as the Hofmeister effect.24 Among the neutral salts
containing monovalent cations such as Na+, Li+, K+, and
In summary, we have demonstrated the effective and se-
lective salt effects on the high yield syntheses of acid-la-
bile epoxides using H2O2 with Na2WO4, [Me(n-
C8H17)3N]HSO4, and PhP(O)(OH)2 or H3PO4 catalysts un-
der not only organic solvent-free but also acidic aqueous
biphasic conditions. The simple addition of a saturated
amount of Na2SO4 strongly promotes the production of
© Georg Thieme Verlag Stuttgart · New York
Synthesis 2012, 44, 1672–1678

1676
H. Hachiya et al.
PAPER
Gram-Scale Epoxidation of Styrene; Typical Procedure for Iso-
lation
A test tube equipped with a magnetic stirring bar was charged with
styrene (1.06 g, 10 mmol), 30% H2O2 (1.14 g, 10 mmol),
Na2WO42H2O (97.2 mg, 0.2 mmol), [Me(n-C8H17)3N]HSO4 (66.1
terpene and styrene oxides due to the suppression of hy-
drolysis without deactivation of the catalytic H2O2 epoxi-
dation system. We consider that the present synthetic
improvement by the addition of salt will be quite promis-
ing for the practical preparation of a variety of acid-labile mg, 0.2 mmol), 5 M aq P(O)(OH)2 (20 μL, 0.1 mmol), and Na2SO4
(0.43 g, 3 mmol). The mixture was vigorously stirred at 25 °C for
epoxides using H2O2.
16 h. After stirring, the two phases were separated, and the organic
phase was washed with 10% aq Na2S2O3 (17 mL). The organic
1H (400 MHz) and 13C NMR (100 MHz) spectra were recorded on
phase was purified by column chromatography on silica gel using
a Jeol ECX-400P spectrometer using CDCl3, CD3OD, and DMSO-
EtOAc as an eluent to give styrene oxide as a colorless oil; yield:
1.01 g (83%).
d6 as solvents. Chemical shifts (δ) are reported in parts per million
1
relative to internal TMS at 0.00 ppm for H and 13C. GC analyses
α-Pinene Oxide26
Yield: 408 mg (89%); colorless oil.
1H NMR (400 MHz, CDCl3): δ = 0.94 (s, 3 H), 1.29 (s, 3 H), 1.34
(s, 3 H), 1.62 (d, J = 9.6 Hz, 1 H), 1.70–1.75 (br m, 1 H), 1.87–2.03
(m, 4 H), 3.07 (dd, J = 4.1, 1.4 Hz, 1 H).
13C NMR (100 MHz, CDCl3): δ = 20.2, 22.4, 25.9, 26.7, 27.6, 39.7,
40.5, 45.1, 56.9, 60.3.
were performed on a Shimadzu GC-17A instrument using a TC-1
column (0.25 mm × 30 m, GL Sciences Inc.). H2O was obtained on
a Millipore Direct-Q UV.
α-Pinene, 3-carene, α-terpineol, terpinen-4-ol, isopulegol, limo-
nene, carvone, sobreol, styrene derivatives, PhP(O)(OH)2, and
[Me(n-C8H17)3N]HSO4 were obtained from Tokyo Chemical Indus-
try Co., Ltd. Na2WO42H2O, 30% aq H2O2, and NaNO3 were ob-
tained from Kanto Chemical Co., Inc. NaHCO3, NaCl, Na2SO4,
(NH4)2SO4, K2SO4, MgSO4, and H3PO4 were obtained from Wako
Pure Chemical Industries., Ltd. Li2SO4 was obtained from Aldrich
Chemical Co.
α-Terpineol Oxide19
Obtained as a 1:1 mixture of cis- and trans-epoxides. Yield: 67%
(GC yield); colorless oil.
1H NMR (400 MHz, CDCl3): δ = 1.01 (qd, J = 12.3, 6.9 Hz, 1 H),
1.13 (s, 3 H), 1.141 (s, 3 H), 1.144 (s, 3 H), 1.16 (s, 3 H), 1.313 (s,
3 H), 1.315 (s, 3 H), 1.43–1.54 (m, 3 H), 1.58–1.69 (m, 3 H), 1.79–
1.94 (m, 2 H), 2.00–2.08 (m, 2 H), 2.19–2.24 (m, 1 H), 3.00 (d, J =
5.5 Hz, 1 H), 3.07 (br, s, 1 H).
13C NMR (100 MHz, CDCl3): δ = 20.1, 22.8, 22.9, 24.4, 25.9, 26.2,
26.6, 27.18, 27.22, 27.4, 29.5, 30.8, 40.2, 44.1, 57.5, 57.7, 59.2,
61.2, 72.2, 72.4.
Epoxidation of α-Pinene; Typical Procedure for GC Analysis
A test tube equipped with a magnetic stirring bar was charged with
α-pinene (475 μL, 3.0 mmol), 30% H2O2 (308 μL, 3.0 mmol),
Na2WO42H2O (19.8 mg, 0.06 mmol), [Me(n-C8H17)3N]HSO4 (29.1
mg, 0.06 mmol), PhP(O)(OH)2 (4.7 mg, 0.03 mmol), and Na2SO4
(129.2 mg, 0.9 mmol). The mixture was vigorously stirred at 25 °C
for 16 h and extracted with toluene (3 × 6 mL). The conversion and
yield were determined by GC analysis of the toluene solution with
ca. 0.2 mmol of n-decane as an internal standard.
Terpinen-4-ol Oxide19b,27
Obtained as a 1:1 mixture of cis- and trans-epoxides; yield: 82%
(GC yield); colorless oil.
Epoxidation of α-Pinene; Typical Procedure for Isolation
A test tube equipped with a magnetic stirring bar was charged with
α-pinene (475 μL, 3.0 mmol), 30% H2O2 (308 μL, 3.0 mmol),
Na2WO42H2O (19.8 mg, 0.06 mmol), [Me(n-C8H17)3N]HSO4 (29.1
mg, 0.06 mmol), PhP(O)(OH)2 (4.7 mg, 0.03 mmol), and Na2SO4
(129.2 mg, 0.9 mmol). The mixture was vigorously stirred at 25 °C
for 16 h. After 16 h, the two phases were separated, and the organic
phase was washed with 10% aq Na2S2O3 (5 mL). The organic phase
was purified by column chromatography on silica gel using EtOAc
as an eluent to give α-pinene oxide as a colorless oil; yield: 408 mg
(89%).
cis-Epoxide
1H NMR (400 MHz, CD3OD): δ = 0.89 (d, J = 7.2 Hz, 3 H), 0.91 (d,
J = 7.2 Hz, 3 H), 1.3–2.4 (m, 7 H), 1.36 (s, 3 H), 3.20 (s, 1 H), 3.53
(s, 1 H).
13C NMR (100 MHz, CD3OD): δ = 6.7, 6.9, 14.0, 15.9, 19.5, 22.0,
27.1, 48.8, 52.3, 62.0.
trans-Epoxide
1H NMR (400 MHz, DMSO-d6): δ = 0.9 (d, J = 7.2 Hz, 6 H), 1.1 (s,
1 H), 1.20–1.24 (m, 2 H), 1.35–1.40 (m, 2 H), 1.65–1.92 (m, 3 H),
2.8 (t, J = 7.0 Hz, 1 H), 4.0 (s, 1 H).
Hydrolysis of α-Pinene Oxide; General Procedure
A test tube equipped with a magnetic stirring bar was charged with
α-pinene oxide (471 μL, 3.0 mmol), 30% H2O2 (308 μL, 3.0 mmol)
or H2O (178 μL, 3.0 mmol), and adding the corresponding neutral
salt as given in Table 1 (0.9 or 1.8 mmol). The mixture was vigor-
ously stirred at 25 °C for 16 h and extracted with toluene (3 × 6 mL).
The conversion and yield were determined by GC analysis of the
toluene solution with ca. 0.2 mmol of n-decane as an internal stan-
dard.
13C NMR (100 MHz, DMSO-d6): δ = 16.1, 16.2, 23.0, 26.3, 29.5,
32.8, 34.5, 57.0, 59.0, 70.0.
Isopulegol Oxide28
Obtained as a 1:1 mixture of cis- and trans-epoxides; yield: 97%
(GC yield); white powder.
cis-Epoxide
1H NMR (400 MHz, CDCl3): δ = 0.80–1.10 (m, 3 H), 0.93 (d, J =
6.6 Hz, 3 H), 1.15–1.27 (m, 1 H), 1.31 (s, 3 H), 1.36–1.52 (m, 1 H),
1.63–1.80 (m, 2 H), 1.98–2.08 (m, 1 H), 2.54 (d, J = 4.8 Hz, 2 H),
2.59 (d, J = 4.8 Hz, 2 H), 2.82 (s, 1 H), 3.71 (dt, J = 4.5, 10.5 Hz, 1
H).
Epoxidation of Styrene; Typical Procedure for GC Analysis
A test tube equipped with a magnetic stirring bar was charged with
styrene (344 μL, 3.0 mmol), 30% H2O2 (308 μL, 3.0 mmol),
Na2WO42H2O (19.8 mg, 0.06 mmol), [Me(n-C8H17)3N]HSO4 (29.1
mg, 0.06 mmol), 5 M aq P(O)(OH)2 (6 μL, 0.03 mmol), and Na2SO4
(129.2 mg, 0.9 mmol). The mixture was vigorously stirred at 25 °C
for 16 hours and extracted with toluene (3 × 6 mL). The conversion
and yield were determined by GC analysis of the toluene solution
with ca. 0.2 mmol of biphenyl as an internal standard.
13C NMR (100 MHz, CDCl3): δ = 16.9, 22.0, 27.7, 30.9, 33.9, 43.5,
51.2, 52.8, 59.1, 71.2.
trans-Epoxide
1H NMR (400 MHz, CDCl3): δ = 0.83–1.18 (m, 3 H), 0.93 (d, J =
6.6 Hz, 3 H), 1.37 (s, 3 H), 1.38–1.52 (m, 2 H), 1.63–1.73 (m, 1 H),
1.83–1.97 (m, 2 H), 2.66 (d, J = 4.2 Hz, 2 H ), 2.92 (d, J = 4.2 Hz,
2 H ), 3.23–3.39 (m, 2 H).
Synthesis 2012, 44, 1672–1678
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H2O2 Epoxidation of Terpenes and Styrenes
1677
13C NMR (100 MHz, CDCl3): δ = 20.8, 22.0, 27.6, 31.1, 33.9, 42.9,
49.0, 52.2, 60.2, 70.5.
trans-β-Methylstyrene Oxide35
Yield: 55% (GC yield); colorless oil.
1H NMR (400 MHz, CDCl3): δ = 1.43 (d, J = 6.8 Hz, 3 H), 3.12 (dq,
J = 6.8, 2.6 Hz, 1 H), 3.55 (d, J = 2.5 Hz, 1 H), 7.27 (m, 5 H).
13C NMR (100 MHz, CDCl3): δ = 17.8, 58.9, 59.4, 125.4, 127.9,
Limonene 2,3-Oxide29
Yield: 89% (GC yield); colorless oil.
1H NMR (400 MHz, CDCl3): δ = 1.13–2.27 (m, 7 H), 1.29 (s, 3 H),
1.71 (s, 3 H), 3.02 (t, J = 5.5 Hz, 1 H), 4.75 (s, 2 H).
128.3, 137.7.
13C NMR (100 MHz, CDCl3): δ = 20.2, 22.1, 25.8, 28.5, 30.7, 40.7,
57.3, 59.2, 109.0, 148.8.
cis-β-Methylstyrene Oxide35
Yield: 89% (GC yield); colorless oil.
1H NMR (400 MHz, CDCl3): δ = 1.08 (d, J = 7.1 Hz, 3 H), 3.33 (dq,
J = 7.1, 5.8 Hz, 1 H), 4.05 (d, J = 5.6 Hz, 1 H), 7.29 (m, 5 H).
13C NMR (100 MHz, CDCl3): δ = 12.5, 55.0, 57.5, 126.5, 127.4,
Carvone 1,6-Oxide30
Yield: 41% (GC yield); colorless oil.
1H NMR (400 MHz, CDCl3): δ = 1.42 (s, 3 H), 1.72 (s, 3 H), 1.91
(dd, J = 15.0, 11.1 Hz, 1 H), 2.03 (dd, J = 17.4, 11.1 Hz, 1 H), 2.38
(dt, J = 15.0, 3.0 Hz, 1 H), 2.59 (dd, J = 17.4, 4.5 Hz, 1 H), 2.67–
2.76 (m, 1 H), 3.46 (d, J = 2.7 Hz, 1 H), 4.72 (s, 1 H), 4.79 (s, 1 H).
13C NMR (100 MHz, CDCl3): δ = 15.2, 20.5, 28.6, 34.9, 41.7, 58.7,
61.2, 110.4, 146.2, 205.4.
127.9, 135.5.
Acknowledgment
This work was partially supported by the New Energy and Industri-
al Technology Development Organization (NEDO), Japan.
Carvone 7,8-Oxide31
Yield: 9% (GC yield); colorless oil.
References
1H NMR (400 MHz, CDCl3): δ = 1.32 (d, J = 6.4 Hz, 3 H), 1.78 (s,
3 H), 2.02–2.70 (m, 7 H), 6.74 (m, 1 H).
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Styrene Oxide32
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α-Methylstyrene Oxide34
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© Georg Thieme Verlag Stuttgart · New York
Synthesis 2012, 44, 1672–1678

1678
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