Epoxidation of α,β-Unsaturated Ketones Using Hydrogen Peroxide in the Presence of Basic Hydrotalcite Catalysts

Article abstract of DOI:10.1021/jo000247e

The basic layered hydrotalcites have been used as catalysts for the epoxidation of α,β-unsaturated ketones in heterogeneous reaction media using hydrogen peroxide as an oxidant. A wide variety of α,β-unsaturated ketones were oxidized to the corresponding epoxyketones in excellent yields under mild reaction conditions. For example, 2-cyclohexen-1-one gave 2,3-epoxycyclohexanone in 91% yield at 40°C for 5 h with high efficiency in hydrogen peroxide. The catalytic activity of the hydrotalcites increased as the basicity of their surfaces increased. In the case of the epoxidation of less reactive substrates, adding a cationic surfactant such as n-dodecyltrimethylammonium bromide (DTMAB) to the above oxidation system accelerated the epoxidation reaction. These hydrotalcite catalysts were easily separated from the reaction mixture and were reusable.

Full text of DOI:10.1021/jo000247e

J . Org. Chem. 2000, 65, 6897-6903
6897
Ep oxid a tion of r,â-Un sa tu r a ted Keton es Usin g Hyd r ogen P er oxid e
in th e P r esen ce of Ba sic Hyd r ota lcite Ca ta lysts
Kazuya Yamaguchi, Kohsuke Mori, Tomoo Mizugaki, Kohki Ebitani, and Kiyotomi Kaneda*
Department of Chemical Science and Engineering, Graduate School of Engineering Science,
Osaka University, 1-3 Machikaneyama, Toyonaka, Osaka 560-8531, J apan
kaneda@cheng.es.osaka-u.ac.jp
Received February 22, 2000
The basic layered hydrotalcites have been used as catalysts for the epoxidation of R,â-unsaturated
ketones in heterogeneous reaction media using hydrogen peroxide as an oxidant. A wide variety of
R,â-unsaturated ketones were oxidized to the corresponding epoxyketones in excellent yields under
mild reaction conditions. For example, 2-cyclohexen-1-one gave 2,3-epoxycyclohexanone in 91% yield
at 40 °C for 5 h with high efficiency in hydrogen peroxide. The catalytic activity of the hydrotalcites
increased as the basicity of their surfaces increased. In the case of the epoxidation of less reactive
substrates, adding a cationic surfactant such as n-dodecyltrimethylammonium bromide (DTMAB)
to the above oxidation system accelerated the epoxidation reaction. These hydrotalcite catalysts
were easily separated from the reaction mixture and were reusable.
In tr od u ction
hydrogen peroxide reacts with a basic hydroxyl function
on the hydrotalcite surface to form a perhydroxyl anion
species (HOO ), which in turn nucleophilically attacks a
Epoxidation of electron-deficient carbon-carbon double
bonds of R,â-unsaturated ketones is of great interest in
organic chemistry because of the synthetic utility of the
resulting intermediates for further functionalization of
ketones.1 In contrast to common olefins, nucleophilic
oxidants are required for the epoxidation of electron-
deficient olefins. Aqueous hydrogen peroxide is an ideal
oxidant because it is both cheap and safe, yielding only
-
nitrile to generate a peroxycarboximidic acid as an active
intermediate oxidant. It is well-known that the epoxida-
tion of R,â-unsaturated ketones using hydrogen peroxide
under alkaline conditions proceeds by nucleophilic attack
3a
of a perhydroxyl anion on olefinic carbons. Since these
hydrotalcite catalysts efficiently transform hydrogen
peroxide into a perhydroxyl anion on the catalyst surface,
we expected that the hydrotalcite-catalyzed system could
be further extended for the epoxidation of R,â-unsatur-
ated ketones.
2
water as a coproduct. The epoxidation of R,â-unsaturated
ketones using hydrogen peroxide under strongly alkaline
conditions with bases such as NaOH, Na
2 3
CO , KOH, and
K
2
CO is still the most common procedure; it is not
3
Here, we report on the efficient heterogeneous epoxi-
dation of R,â-unsaturated ketones by hydrogen peroxide
using hydrotalcite catalysts under mild reaction condi-
tions (eq 1). This heterogeneous hydrotalcite system can
applicable for base-sensitive substrates such as cyclo-
pentenones unless the pH of the reaction media is strictly
controlled. Moreover, the use of such bases is undesirable
because they are hazardous and lead to the production
of a vast amount of wastes. With ever-growing environ-
mental concern, much attention has been paid to the
development of a “green protocol” using a “green oxidant”
like hydrogen peroxide in a combination with reusable
(3) The following are works on the epoxidation of R,â-unsaturated
carbonyl compounds using hydrogen peroxide as an oxideant: (a)
Bunton, C. A.; Minkoff, G. J . J . Chem. Soc. 1949, 665. (b) Greco, P. A.;
Nishizawa, H.; Oguri, T.; Burkee, S. D.; Marinovic, N. J . Am. Chem.
Soc. 1977, 99, 5773. (c) J ulia, S.; Guixer, J .; Masana, J .; Rocas, J .;
Colonna, S.; Molinari, H. J . Chem. Soc., Perkin Trans. 1 1982, 1317.
(d) Ishii, Y.; Sakata, Y. J . Org. Chem. 1990, 55, 5545. (e) Banfi, S.;
Colonna, S.; Molinari, H.; J ulia, S.; Guixer, J ., Tetrahedron 1984, 40,
3
solid catalysts.
We have recently developed a series of hydrotalcite
catalysts as solid bases for various oxidation reactions
5
207. (f) Schulz, M.; Kluge, R.; Lipke, M. Synlett 1993, 915. (g)
using hydrogen peroxide or molecular oxygen as an
Cativiela, C.; Figueras, F.; Fraile, J . M.; Garc ´ı a, J . I.; Mayoral, J . A.
Tetrahedron Lett. 1995, 36, 4125. (h) Kim, Y. H.; Hwang, J . P.; Yang,
S. G. Tetrahedron Lett. 1997, 38, 3009. (i) Choudary, B. M.; Kantam,
M. L.; Bharathi, B.; Reddy, C. V. Synlett 1998, 1203.
oxidant.4 The hydrotalcite, Mg10Al
-8
2 3
(OH)24CO , in the
presence of an oxidant composed of hydrogen peroxide
and a nitrile had high catalytic activity for the epoxida-
tion of unfunctionalized olefins.7 In such epoxidations,
(4) For Baeyer-Villiger oxidation of ketones, see: (a) Kaneda, K.:
a
Ueno, S.; Imanaka, T. J . Chem. Soc., Chem. Commun. 1994, 797. (b)
Kaneda, K.; Ueno, S.; Imanaka, T. J . Mol. Catal. 1995, 102, 135. (c)
Kaneda, K.; Yamashita, T. Tetrahedron Lett. 1996, 37, 4555. (d) Ueno,
S.; Ebitani, K.; Ookubo, A.; Kaneda, K. Appl. Surf. Sci. 1997, 121/
122, 366.
*
Phone and Fax: +81-6-6850-6260.
1) (a) Parker, R. E.; Isaacs, N. S. Chem. Rev. 1959, 59, 737. (b) Rao,
A. S. Paknikar, S. K.; Kirtane, J . G. Tetrahedron Lett. 1983, 39, 2323.
c) Smith, G. J . Synthesis 1984, 629. (d) Kotsuki, H.; Kataoka, M.;
(
(5) For the oxidative dehydrogenation of alcohols, see: Kaneda, K.;
Yamashita, T.; Matsushita, T.; Ebitani, K. J . Org. Chem. 1998, 63,
1750.
(6) For the oxygenation of aromatic compounds, see: Matsushita,
T.; Ebitani, K.; Kaneda, K. Chem. Commun. 1999, 265.
(7) For the epoxidation of olefins, see: (a) Ueno, S.; Yamaguchi, K.;
Yoshida, K.: Ebitani, K.; Kaneda, K. Chem. Commun. 1998, 295. (b)
Yamaguchi, K.; Ebitani, K.; Kaneda, K. J . Org. Chem. 1999, 64, 2966.
(8) For the N-oxidation of pyridines, see: Yamaguchi, K.; Mizugaki,
T.; Ebitani, K.; Kaneda, K. New J . Chem. 1999, 23, 799.
(
Nishizawa, H. Tetrahedron Lett. 1993, 34, 4031. (e) Alcaraz, L.;
Harnett, J . J .; Mioskowski, C.; Martel, J .-P.; Gall, T. L.; Shin, D.-S.;
Falck, J . R. Tetrahedron Lett. 1994, 35, 5449.
(2) (a) Green Chemistry: Theory and Practice; Anastas, P. T.,
Warner, J . C., Eds.; Oxford University Press: New York, 1998. (b)
Clark, J . H. Green Chem. 1999, 1, 1. (c) Sheldon, R. A. Green Chem.
2
000, 2, G1. (d) Anastas, P. T.; Bartlett, L. B.; Kirchhoff, M. M.;
Williamson, T. C. Catal. Today 2000, 55, 11.
1
0.1021/jo000247e CCC: $19.00 © 2000 American Chemical Society
Published on Web 09/19/2000

6
898 J . Org. Chem., Vol. 65, No. 21, 2000
Yamaguchi et al.
Ta ble 1. Effect of Solven ts on th e Ep oxid a tion of
Ta ble 2. Recyclin g of th e Mg10Al2(OH)24CO3 Ca ta lyst in
a
2
-Cycloh exen -1-on e Ca ta lyzed by Mg10Al2(OH)24CO3
th e Ep oxid a tion of 2-Cycloh exen -1-on e
a
Usin g H2O2
convn of
cyclohexenone (%)
yield of
epoxyketone (%)
b
b
yield of
epoxyketone (%)
run
convnb (%)
b
entry
solvent
methanol
1
(fresh)
94
91
92
91
91
90
90
89
1
2
3
4
5
6
7
78
30
15
79
87
77
71
74
26
10
78
84
77
71
2
3
4
ethanol
2-propanol
ethyl acetate
1,2-dichloroethane
n-heptane
a
Reaction conditions: cyclohexenone (2 mmol), Mg10Al2(OH)24CO3
0.15 g), 30% aq H2O2 (0.9 mL, 8 mmol), methanol (5 mL), 40 °C,
(
b
5
h. Determined by GC using an internal standard technique.
cyclohexane
a
Reaction conditions: cyclohexenone (2 mmol), Mg10Al2(OH)24CO3
equiv of hydrogen peroxide in methanol solvent. High
efficiency in hydrogen peroxide utilization was observed
when the reaction was performed at low temperatures.
However, attaining high yields of the epoxyketone re-
quired long reaction times below 20 °C, e.g., 82% yield
at 20 °C for 48 h. The increase of reaction temperatures
over 60 °C resulted in a decrease in efficiency; when the
reaction temperature was changed from 40 to 60 °C, 85%
yield of the epoxyketone after 24 h dropped to 73%.
Epoxidation at 40 °C was the most suitable from the
standpoints of the efficiency of hydrogen peroxide and
the reaction rate.
(
0.15 g), 30% aq H2O2 (0.9 mL, 8 mmol), solvent (5 mL), 40 °C, 2
b
h. Determined by GC using an internal standard technique.
be regarded as an environmentally friendly chemical
process because it uses 30 wt % aqueous hydrogen
peroxide, a simple workup procedure, and a reusable
catalyst. In addition, cationic surfactants act as phase-
transfer reagents to promote the epoxidation.
The use of a solid hydrotalcite makes the workup
procedure very simple. The spent hydrotalcite, Mg10Al
2
-
(
OH)24CO , was easily separated from the reaction mix-
3
ture by a simple filtration. The recovered catalyst was
then reused for the epoxidation of 2-cyclohexen-1-one.
The results are summarized in Table 2. The oxidation
using the spent catalyst gave the epoxyketone in 90%
yield under the same conditions as those of the first run.
In the same manner, third and forth runs afforded the
epoxyketone in 90% and 89% yields, respectively.
1-2. Ep oxid a tion of Va r iou s r,â-Un sa tu r a ted Ke-
ton es. Oxidations of various R,â-unsaturated ketones
2 3
using Mg10Al (OH)24CO were carried out in methanol
Resu lts a n d Discu ssion
1
. Tr ip h a sic Ep oxid a tion System . 1-1. Su r vey of
Rea ction Con d ition s. Oxidations of 2-cyclohexen-1-one
as a model substrate using 30 wt % aqueous hydrogen
peroxide in various solvents were carried out in the
2 3
presence of the hydrotalcite, Mg10Al (OH)24CO . The
results are summarized in Table 1. 1,2-Dichloroethane
was the most effective solvent for this oxidation; 2,3-
epoxycyclohexanone was formed in 84% yield (40 °C, 2
h, entry 5). However, the use of halogenated solvents is
solvent at 40 °C and are summarized in Table 3. Simple
cyclic enones such as cyclopentenone and cyclohexenone
were smoothly oxidized to form the corresponding ep-
oxyketones. 2-Cyclohexen-1-one was converted into 2,3-
epoxycyclohexanone in 91% yield for 5 h (entry 3). A
â-substituted cyclohexenone of 3-methyl-2-cyclohexen-1-
one gave a high yield of the corresponding epoxyketone
when the reaction time was prolonged to 24 h (entry 4).
It is said that selective epoxidation of cyclopentenone is
not attainable under basic conditions using NaOH and
KOH because of competing aldol-type condensation.
Notably, in the hydrotalcite catalyst system, 97% of 2,3-
epoxycyclopentanone could be obtained from 2-cyclo-
penten-1-one in 3 h without formation of the aldol
products (entry 1). Further, an alkyl-substituted cyclo-
pentenone of 3-methyl-2-cyclopenten-1-one also could give
the corresponding epoxyketone in excellent yield (entry
2). The oxidation of 1,4-naphthoquinone was very fast,
affording the epoxyketone in an almost quantitative yield
within 1 h (entry 5). Simple cyclic enones gave high yields
of the corresponding epoxides, but the epoxidation of
acyclic enones was difficult using the above reaction
system. 4-Hexen-3-one, an aliphatic R,â-unsaturated
ketone, was hardly oxidized under the above reaction
conditions (entry 6). Further, oxidation of chalcone
resulted in only 57% yield of 2,3-epoxy-1,3-diphenylpro-
panone (entry 7).
2
undesirable from an environmental point of view. There-
fore, we had to try to use nonhalogenated solvents. It was
then found that ethyl acetate, n-heptane, methanol, and
cyclohexane were also good solvents, affording 78%, 77%,
7
4%, and 71% yields of the epoxyketone under the same
reaction conditions, respectively (entries 1, 4, 6, and 7).
Ethanol and 2-propanol were poor solvents (entries 2 and
3
).
To optimize the amount of hydrogen peroxide required,
epoxidations of 2-cyclohexen-1-one were carried out using
various oxidant stoichiometries at 40 °C in methanol.
When 4 equiv of hydrogen peroxide to a substrate were
used, 2-cyclohexen-1-one gave an almost quantitative
yield of the epoxyketone within 5 h. The epoxidation rate
was slightly improved when a greater than 4-fold excess
of hydrogen peroxide was used. It is notable that excellent
efficiency in hydrogen peroxide utilization could also be
attained in this reaction system. For example, 2,3-epoxy-
cyclohexanone was obtained in 85% yield with only 1
equiv of hydrogen peroxide in methanol, although the
reaction time was 24 h. The use of ethyl acetate, cyclo-
hexane, and n-heptane solvents afforded the epoxyketone
in 61%, 61%, and 58% yields, respectively.
The effect of reaction temperatures on the efficiency
of hydrogen peroxide utilization was also examined in
the case of the oxidation of 2-cyclohexen-1-one using 1
To explain the reactivity of the above R,â-unsaturated
ketones, orbital energies in the LUMO of substrates 1-7

Epoxidation of R,â-Unsaturated Ketones
J . Org. Chem., Vol. 65, No. 21, 2000 6899
Ta ble 3. Ep oxid a tion of Va r iou s r,â-Un sa tu r a ted Keton es Ca ta lyzed by Mg10Al2(OH)24CO3 Usin g H2O2 in Meth a n ola
a
Reaction conditions: substrate (2 mmol), Mg10Al2(OH)24CO3 (0.15 g), 30% aq H2O2 (0.9 mL, 8 mmol), methanol (5 mL), 40 °C.
Determined by GC or HPLC using an internal standard technique. Values in parentheses are isolated yields. For the isolation experiment,
b
the reaction scale was three times as much as that of reaction conditions a. c Orbital energies in the LUMO were calculated by the PM3
semiempirical method.
9
were calculated (Table 3). The orbital energies in the
LUMO can be regarded as a measure of the electrophi-
licity of these enones.10 The substrates 1, 3, and 5 having
low LUMO orbital energies showed high reactivity for
this epoxidation. The lower reactivity of substituted cyclic
enones of 2 and 4 compared with nonsubstituted ones of
organic reactions by increasing the contact area of the
1
1,12
interface between water and organic phases.
Since
this oxidation occurs at the interface between water and
organic phases, we expected that the use of surfactants
might enhance the epoxidation of poorly reactive sub-
strates such as 4-hexen-3-one and chalcone.
1
, 3, and 5 might be due to the steric hindrance about
The effect of various surfactants on the epoxidation of
chalcone was examined in n-heptane solvent as shown
in Table 4. Interestingly, the use of cationic surfactants
olefinic double bonds. Vide supra, 4-hexen-3-one has a
high LUMO orbital energy and gave an extremely low
yield of the epoxyketone. The low reactivity of chalcone
despite its low LUMO orbital energy might be related to
its solubility into the water phase; the solubility is 0.16
mM for chalcone, whereas it is 157.7 mM for 2-cyclo-
hexen-1-one at 25 °C.
having long alkyl chains such as [CH
(DTMAB), [CH (CH ]Br, and [(n-C12
gave high yields of 2,3-epoxy-1,3-diphenylpropanone
(entries 2, 4, and 6), while [CH (CH N(CH ]Br and [(n-
N]Br having short alkyl chains were not effective
(entries 1 and 5). Both an anionic surfactant [CH (CH
SO ]Na (SDS) and a nonionic surfactant of sorbitan
3
(CH
2
)11N(CH
3
)
3
]Br
3
2
)15N(CH
3
)
3
25 4
H ) N]Br
3
2
)
7
3 3
)
4 9 4
C H )
2
. Ep oxid a tion u n d er th e P h a se-Tr a n sfer Con d i-
3
2 11
) -
tion s. 2-1. Su r fa cta n t Effect. The above epoxidation
mixture contains three phases: an organic ketone phase,
an aqueous phase containing hydrogen peroxide, and the
solid hydrotalcites. It is well-known that in a biphasic
medium, surfactants can enhance the rates of many
4
monolaurate (span 20) failed to promote the epoxidation
(11) Mathias, L. J .; Vaidys, R. A. J . Am. Chem. Soc. 1986, 108, 1093
and references cited therein.
(12) Recently, phase-transfer oxidation systems using hydrogen
peroxide have been developed. The followings are excellent examples
of epoxidation under phase-transfer conditions: (a) Sakaguchi, S.;
Nishiyama, Y.; Ishii, Y. J . Org. Chem. 1996, 61, 5307. (b) Boyer, B.;
Hambardzoumian, A.; Lamaty, G.; Leydet, A.; Roque, J .-P.; Bouchet,
P. New J . Chem. 1996, 20, 985. (c) Sato, K.; Aoki, M.; Ogawa, M.;
Hashimoto, T.; Panyella, D.; Noyori, R. Bull. Chem. Soc. J pn. 1997,
70, 905. (d) Boyer, B.; Hambardzoumian, A.; Roque, J .-P. Tetrahedron
1999, 55, 6147.
(
9) The geometries of R,â-unsaturated ketones were calculated by
the PM3 semiempirical method as implemented in the MOPAC version
7 system. The calculation was performed to localize the olefinic double
9
bonds of R,â-unsaturated ketones into the XY plane: Stewart, J . J . P.
J . Comput. Chem. 1989, 10, 221.
(10) Loncharich, R. J .; Brown, F. K.; Houk, K. N. J . Org. Chem. 1989,
5
4, 1129.

6
900 J . Org. Chem., Vol. 65, No. 21, 2000
Yamaguchi et al.
Ta ble 4. Effect of Su r fa cta n ts on th e Ep oxid a tion of
Ch a lcon e Ca ta lyzed by Mg10Al2(OH)24CO3 Usin g H2O2a
of R,â-unsaturated ketones. Typical examples are col-
lected in Table 5. Oxidations of common open-chain R,â-
unsaturated ketones proceeded smoothly to give epoxyke-
tones in high yields (entries 1-5). In the oxidation of the
open-chain ketones using calcined hydrotalcites, Cativiela
et al. reported the formation of 1,2-dioxolane products;
mesityl oxide and 4-hexen-3-one gave the corresponding
yield of
convnb epoxyketoneb
entry
surfactant
(%)
(%)
1
2
3
4
5
6
7
8
9
[CH3(CH2)7N(CH3)3]Br
[CH3(CH2)11N(CH3)3]Br
[CH3(CH2)11N(CH3)3]Br
[CH3(CH2)15N(CH3)3]Br
[(n-C4H9)4N]Br
12
100
3
100
5
100
3
5
12
98
3
96
3
96
3
5
c
3
-hydroxy-1,2-dioxolanes in 36 %and 22% yields, respec-
3
g
tively. Using our catalyst system, 13% yield of 3-hy-
droxy-3,3,5-trimethyl-1,2-dioxolane was obtained as a
byproduct in the case of mesityl oxide (entry 1). Other
open-chain aliphatic enones such as 4-hexen-3-one and
[(n-C12H25)4N]Br
[CH3(CH2)11SO4]Na
sorbitan monolaurate (span 20)
without
2
2
3
-nonen-2-one gave high yields of epoxyketones as sole
a
Reaction conditions: chalcone (2 mmol), Mg10Al2(OH)24CO3
products, respectively (entries 2 and 3).
(
0.15 g), 30% aq H2O2 (0.9 mL, 8 mmol), n-heptane (5 mL),
Generally, the epoxidation of isophorone does not easily
proceed as a result of the steric hindrance of the
b
surfactant (0.3 mmol), water (3 mL), 40 °C, 2 h. Determined by
c
HPLC using an internal standard technique, Without hydrotalcite
1
3
â-substituted methyl group and gem-dimethyl group.
catalyst.
Isophorone, however, could be efficiently oxidized to form
epoxyisophorone in 95% yield with this system (entry 7).
In the case of (R)-(-)-carvone, hydrotalcite catalysts
resulted in regioselective oxidation of the conjugated
double bond to afford 2,3-epoxy-5-isopropenyl-2-methyl-
cyclohexanone as a single diastereomer with the methyl
group cis to the isopropenyl group (entry 8).1 A similar
selective formation of the cis-carvone oxide can be also
observed in the base-catalyzed epoxidation using the
hydrogen peroxide/NaOH system.14
4
The â,â-disubstituted acyclic enone, pulegone, hardly
gave any epoxyketone, even after 48 h. Pulegone has high
orbital energies both in the LUMO and HOMO, 0.273
and -9.605 eV, respectively. It is likely that electrophilic
oxidants such as peracids might be preferable to a
-
nucleophilic HOO species for the epoxidation of pule-
gone. Indeed, using a combined oxidant of benzonitrile
7
a
and hydrogen peroxide in the presence of hydrotalcites,
pulegone could be smoothly oxidized to give the corre-
sponding epoxyketone in 93% yield (eq 2).
2 3
F igu r e 1. Reaction profiles of the Mg10Al (OH)24CO -catalyzed
epoxidation of chalcone in (a) n-heptane with DTMAB, (b)
methanol with DTMAB, (c) methanol without DTMAB, and
(d) n-heptane without DTMAB.
3
. Ca ta lyst Effect a n d Rea ction Mech a n ism . Oxi-
dations of isophorone using various kinds of base cata-
lysts carried out in the presence of DTMAB are shown
in Table 6. Yields of the epoxyketone increased with an
increase in the heat of benzoic acid adsorption on
hydrotalcites (entries 1, 3, and 5). The calorimetric heat
of benzoic acid adsorption can be regarded as a measure
of the basicity of the solid surfaces.4d The catalytic activity
of MgO was lower than those of hydrotalcites and Mg-
(
entries 7 and 8 vs entry 2). In addition, oxidation without
the hydrotalcite catalyst gave only 3% of the epoxyketone
even in the presence of DTMAB (entry 3).
Oxidations of chalcone using DTMAB or no surfactant
were carried out in various solvents at 40 °C, as shown
in Figure 1. Adding DTMAB to the above oxidation
system remarkably accelerated yields of the epoxyketone,
particularly when nonpolar solvents such as n-hexane,
cyclohexane, and n-heptane were used. For example, a
quantitative yield of the epoxyketone was obtained in
n-heptane within 2 h, while the epoxidation hardly
proceeded in the absence of DTMAB. The use of methanol
in the presence of DTMAB gave the epoxyketone in only
(OH)
2
, although MgO possesses a strong basicity (entry
6
). The use of NaOH as a base catalyst resulted in a low
selectivity as a result of oxidative cleavage of the ep-
oxyketone to form 3,3-dimethyl-5-oxohexanoic acid (entry
1
5
9
). It is said that the calcined hydrotalcites of Mg-Al
mixed oxides have high Lewis basicity derived from the
4
6% yield after 4 h.
Further, a similar phenomenon was observed also in
surface oxygen species.16 However, their catalytic activi-
the epoxidation of 2-cyclohexen-1-one (Table 5, entry 6).
It is clear that this phase-transfer procedure by the use
of DTMAB is very effective, especially for the epoxidation
of hydrophobic enone substrates.
(
13) (a) Yadav, V. K.; Kapoor, K. K. Tetrahedron Lett. 1994, 35, 9481.
(
b) Straub, T. S. Tetrahedron Lett. 1995, 36, 663. (c) Fraile, J . M.;
Garc ´ı a, J . I.; Cativiela, C.; Mayoral, J . A.; Figueras, F. Tetrahedron
Lett. 1996, 37, 5995.
(
14) Lindquist, N.; Battiste, M. A.; Whitten, W. M.; Williams, N.
2
-2. Su bstr a te Scop e. This phase-transfer procedure
H.; Strekowski, L. Phytochemistry 1985, 24, 683.
(15) Temple, R. D. J . Org. Chem. 1970, 35, 1275.
using DTMAB could be widely applied to various kinds

Epoxidation of R,â-Unsaturated Ketones
J . Org. Chem., Vol. 65, No. 21, 2000 6901
Ta ble 5. Ep oxid a tion of Va r iou s r,â-Un sa tu r a ted Keton es Ca ta lyzed by Mg10Al2(OH)24CO3 Usin g H2O2 u n d er
P h a se-Tr a n sfer Con d ition s w ith DTMABa
a
Reaction conditions: substrate (2 mmol), Mg10Al2(OH)24CO3 (0.15 g), 30% aq H2O2 (0.9 mL, 8 mmol), n-heptane (5 mL), DTMAB (0.3
b
mmol), water (3 mL), 40 °C. Determined by GC or HPLC using an internal standard technique. Values in parentheses are isolated
c
yields. For the isolation experiment, the reaction scale was three times as much as that of reaction conditions a. Yields were determined
1
by H NMR of the reaction mixture. 3-Hydroxy-3,3,5-trimethyl-1,2-dioxolane was also formed in 13% yield.
ties were slightly lower than those of the corresponding
uncalcined hydrotalcites (entries 1 vs 2 and 3 vs 4). The
XRD spectra revealed that calcined hydrotalcites were
hydrated partially to rebuild the original hydrotalcite
structure under our reaction conditions using aqueous
hydrogen peroxide. Moreover, the calcined hydrotalcites
have not only strong basic sites but also acidic sites.16
Vide supra, in the oxidation of open-chain aliphatic
enones using calcined hydrotalcites, the selectivities to
epoxyketones were undesirable because of the acid-
catalyzed formation of 1,2-dioxolanes.3g,17 These results
Ta ble 6. Ep oxid a tion of Isop h or on e Ca ta lyzed by
Va r iou s Ba ses Usin g H2O2a
convn of
yield of
heat of
isophorone epoxyketoneb adsorptionc
-
1
entry
1
catalyst
(%)
(%)
(J g )
Mg10Al2(OH)24CO3
97
88
77
69
61
51
60
8
95
84
73
62
61
40
60
7
14.2
20.2
6.3
16.9
5.1
8.4
6.4
1.8
d
2
3
4
5
6
7
8
9
0
1
Mg10Al (OH)24CO3
2
Mg6Al2(OH)16CO3
d
Mg6Al2(OH)16CO3
Mg6Al2(OH)16SO4
MgO
Mg(OH)2
Al(OH)3
NaOH
Na2CO3
without
e
(
16) We have recently reported that the Mg-Al mixed oxides
obtained by calcination of hydrotalcites were effective acid-base
bifunctional catalysts for the fixation of CO to various epoxides to
f
g
81
53
<1
70
47
<1
f
1
1
2
form five-membered cyclic carbonates: Yamaguchi, K.; Ebitani, K.;
Yoshida, T.; Yoshida, H.; Kaneda, K. J . Am. Chem. Soc. 1999, 121,
a
Reaction conditions: isophorone (2 mmol), catalyst (0.15 g),
4
526.
17) It is known that 1,2-dioxolane compounds are formed by 1,4-
n-heptane (5 mL), DTHMAB (0.3 mmol), water (3 mL), 30% aq
H2O2 (0.9 mL, 8 mmol), 40 °C, 24 h. Yields of the epoxide were
determined by GC. See ref 4d. Catalysts calcined at 400 °C were
used. e MgO calcined at 400 °C was used. f 0.2 mmol. g 3,3-Dimeth-
yl-5-oxohexanoic acid was also formed as a byproduct.
(
b
addition reaction of hydrogen peroxide to the enone such as mesityl
oxide and 4-hexen-3-one under acidic conditions: (a) Rieche, A.;
Schmitz, E.; Gr u¨ ndemann, E. Angew. Chem. 1960, 72, 635. (b) Rieche,
A.; Schmitz, E.; Gr u¨ ndemann, E. Chem. Ber. 1960, 93, 2443.
c
d

6
902 J . Org. Chem., Vol. 65, No. 21, 2000
Yamaguchi et al.
Sch em e 1
after the calcination at 400 °C. Hydrogen peroxide (30 wt %)
and various kinds of surfactants were purchased from Wako
Pure Chemical and used as received. R,â-Unsaturated ketones
as substrates and solvents were purified by the standard
procedures before use.18 All of the epoxidation products are
well-known compounds. Their identities were confirmed by
1
13
comparison with mass spectroscopy and H and C NMR and
infrared spectra.1
4,19
Gen er a l P r oced u r e for P r ep a r a tion of Hyd r ota lcite
Ca ta lysts. Various hydrotalcites were prepared by the litera-
ture procedure.20 A typical example is for Mg10Al
(OH)24CO
O (0.05 mol) were
dissolved in deionized water (100 mL), and a second water
solution (60 mL) of Na CO (0.03 mol) and NaOH (0.07 mol)
2
3
.
indicate that basic sites due to the surface hydroxyl
groups on uncalcined hydrotalcites might play an impor-
tant role in this selective epoxidation.
Al(NO
3
)
3
‚9H
2
O (0.01 mol) and Mg(NO
3
)
2
‚6H
2
2
3
A possible reaction mechanism for this epoxidation is
shown in Scheme 1. Hydrogen peroxide reacts with a
basic hydroxyl function on the surface of a hydrotalcite
to form a perhydroxyl anion. This anionic species attacks
the â-olefinic carbon atom of an R,â-unsaturated ketone,
followed by the ring enclosure to give the corresponding
epoxyketone, which regenerates the surface hydroxyl
function of the hydrotalcite. Vide supra, R,â-unsaturated
ketones having low LUMO orbital energies show high
reactivity. The above results support that this epoxida-
tion can occur via a nucleophilic attack of a perhydroxyl
species. Oxidation of less reactive substrates with high
LUMO energies and/or low solubility into the water
phase is strongly promoted by cationic surfactants. Under
these phase-transfer conditions, it is likely that a per-
hydroxyl anion species interacts with quaternary am-
was prepared. After the first solution was slowly added to the
second one, the resulting mixture was heated at 65 °C for 18
h with vigorous stirring. The white slurry was then cooled to
room temperature, filtered, washed with large amount of
deionized water, and dried overnight at 110 °C. The basal
spacing was 7.93 Å determined from the XRD measurement.
These hydrotalcite catalysts were stored in air and used
without further pretreatment.
Mea su r em en t of th e Ba sicity of Ca ta lysts. The calori-
metric heats of benzoic acid adsorption on the catalysts were
4d
measured by using a microdifferential scanning calorimeter.
Catalyst (10 mg) was added into a cyclohexane solution (0.5
mL), and then a solution of benzoic acid (0.005 mmol) in
cyclohexane (0.2 mL) was added into the above solution. The
heat of generation was regarded as the calorimetric heat of
benzoic acid adsorption.
Gen er a l P r oced u r e for th e Ep oxid a tion w ith Hyd r o-
ta lcite Ca ta lysts. Typical hydrotalcite-catalyzed epoxidation
of R,â-unsaturated ketones is accomplished as follows. Into a
reaction vessel with a reflux condenser were successively
+
monium cation (Q ) and then moves into organic phase
+
-
by forming an ion pair such as a Q HOO species in order
to react with a lipophilic R,â-unsaturated ketone sub-
strate. The long alkyl chains of cationic surfactants bring
about increasing the lipophilicity of cationic surfactant
molecules, which facilitates the transporting of a lipo-
philic enone from the organic phase to the interface as a
reaction zone. We think that main roles of the cationic
surfactants are (1) to increase the contact area of the
interface between water and organic phases, (2) to ensure
the transfer of a substrate from the organic phase to the
surface boundary, and (3) to gather the perhydroxyl anion
from the water phase to the surface boundary.
placed the hydrotalcite of Mg10Al
2 3
(OH)24CO (0.45 g), methanol
(15 mL), 2-cyclohexen-1-one (6 mmol), and 30% aqueous
hydrogen peroxide (2.7 mL, 24 mmol). After the resulting
mixture was stirred at 40 °C for an appropriate time, the
hydrotalcite was separated by a filtration. The filtrate was
2
treated with MnO , followed by extraction with ethyl acetate
(
25 mL × 3). The extract was concentrated and subjected to
column chromatography on silica gel (Wako gel C-200) with a
mixture of n-hexane and ether (3:1) to afford 0.61 g of pure
2
,3-epoxycyclohexanone (90% yield).
Gen er a l P r oced u r e for th e Hyd r ota lcite-Ca ta lyzed
Ep oxid a tion u n d er P h a se-Tr a n sfer Con d ition s. A typical
example for the epoxidation under the phase-transfer condi-
tions is as follows. Into a reaction vessel with a reflux
Con clu sion
condenser were successively placed the hydrotalcite of Mg10
-
Solid hydrotalcites efficiently catalyze the epoxidation
of various kinds of R,â-unsaturated ketones using hy-
drogen peroxide under mild reaction conditions. In this
epoxidation, basic sites due to surface hydroxyl functions
of hydrotalcites promote the transformation of hydrogen
peroxide into the perhydroxyl anion as an active species.
For less reactive substrates, the phase-transfer procedure
using a cationic surfactant of DTMAB is very effective
for facile formation of epoxyketones. Further, these
hydrotalcite catalysts are easily separated from the
reaction mixture and can be reused with retention of
their high catalytic activity and selectivity. We believe
that this hydrotalcite-catalyzed system could have high
potential in a wide variety of environment-friendly
organic syntheses.
Al (OH)24CO (0.45 g), methanol (15 mL), chalcone (6 mmol),
2
3
30% aqueous hydrogen peroxide (2.7 mL, 24 mmol), dodecyl-
trimethylammonium bromide (DTAB) (0.3 mmol), and water
(0.9 mL). After the resulting mixture was stirred at 40 °C for
an appropriate time, affording 1.10 g of pure 2,3-epoxy-1,3-
diphenylpropanone (82% yield).
Recyclin g of th e Hyd r ota lcite Ca ta lyst for th e Ep oxi-
d a tion of 2-Cycloh exen -1-on e. Using the same procedure
as described in the above, the first run for 2-cyclohexen-1-one
(2 mmol scale) was carried out. After the oxidation, the spent
hydrotalcite was recovered by filtration. The isolated hydro-
talcite was washed with a small portion of deionized water
and dried overnight at 110 °C before reuse. These recycling
procedures were repeated three times in the same manner as
for the first recycle.
(
18) Purification of Laboratory Chemicals, 3rd ed.; Perrin, D. D.,
Armarego, W. L. F., Eds; Pergamon Press: Oxford, U.K., 1988.
19) (a) Wyneberg, H.; Marsman, B. J . Org. Chem. 1980, 45, 158.
b) Reed, K. L.; Gupton, J . T.; Solarz, T. L. Synth. Commun. 1989, 19,
Exp er im en ta l Section
(
(
Gen er a l. Al(NO
Mg(OH) were purchased from Wako Pure Chemical as a
3
)
3
‚9H
2
O, Al(OH)
3
, Mg(NO
3
)
2
2
‚6H O, and
3
1
579. (c) Adam, W.; Hadjiarapoglou, L.; Nester, B. Tetrahedron Lett.
990, 31, 331. (d) Straub, T. S. Tetrahedron Lett. 1995, 36, 663.
(20) (a) Miyata, S. Clays Clay Miner. 1980, 28, 50. (b) Cavani, F.;
2
special grade. MgO was supplied from the Catalyst Society of
J apan as a reference catalyst, J RC-MGO-4 (1000 A) and used
Trifir o` , F.; Voccari, A. Catal. Today 1991, 11, 173.

Epoxidation of R,â-Unsaturated Ketones
J . Org. Chem., Vol. 65, No. 21, 2000 6903
Ack n ow led gm en t. This work is supported by a
Grant-in-Aid for Scientific Research from the Ministry
of Education, Science, Sports and Culture of J apan
grateful to the Department of Chemical Science and
Engineering, Osaka University, for scientific support by
the Gas-Hydrate Analyzing System (GHAS).
(
11450307). We thank Prof. Yasunori Yoshioka at Osaka
University for his help in MO calculations. We are also
J O000247E