Iron-catalyzed epoxidation of olefins using hydrogen peroxide

Article abstract of DOI:10.1039/c0gc00943a

A practical method of olefin epoxidation was developed by combining FeCl₃·6H₂O and 1-methylimidazole in acetone using H₂O₂ as the terminal oxidant. This system showed very good reactivity toward epoxidation of both terminal and substituted alkenes. The use of tridentate and tetradentate amine-bis(phenolate) ligands as additives was also examined. Modest improvement in selectivity was achieved if a bulky tridentate ligand was used. Generally, however, the simple catalyst system involving ferric chloride, 1-methylimidazole and dilute H₂O ₂ in acetone proved most successful in achieving good to excellent yields of epoxide products for a number of substrates, including aromatic and aliphatic alkenes.

Full text of DOI:10.1039/c0gc00943a

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PAPER
Iron-catalyzed epoxidation of olefins using hydrogen peroxide†
Kamrul Hasan, Nicole Brown and Christopher M. Kozak*
Received 22nd December 2010, Accepted 22nd February 2011
DOI: 10.1039/c0gc00943a
A practical method of olefin epoxidation was developed by combining FeCl
3
·6H
2
O and
1
-methylimidazole in acetone using H as the terminal oxidant. This system showed very good
2
O
2
reactivity toward epoxidation of both terminal and substituted alkenes. The use of tridentate and
tetradentate amine-bis(phenolate) ligands as additives was also examined. Modest improvement
in selectivity was achieved if a bulky tridentate ligand was used. Generally, however, the simple
catalyst system involving ferric chloride, 1-methylimidazole and dilute H
2
2
O in acetone proved
most successful in achieving good to excellent yields of epoxide products for a number of
substrates, including aromatic and aliphatic alkenes.
Introduction
ever, recent development of Mn catalysts for the epoxidation
of alkenes was explored by heterogeneous Mn(II) exchanged
19
Metal-catalyzed oxygenation of organic substrates is becoming
an increasingly important reaction in modern organic synthesis.
zeolites in a bicarbonate solution and a SiO
Mn(II) complex in an ammonium acetate solution. In the
SiO -immobilized Mn(II) acetylacetonate system, the active
2
-immobilized
1
20
The development of catalytic epoxidation agents that are
rapid, selective, scalable, and inexpensive with a wide substrate
scope remains an important goal. Olefins are one of the
most important starting materials for organic synthesis and
their oxidation leads to various value-added products such as
epoxides, alcohols, aldehydes, ketones, and carboxylic acids.
These in turn are important building blocks for the production of
bulk and fine chemicals. The quest for clean, selective oxidation
processes has been motivated by the need for atom efficient
technologies adhering to the principles of green chemistry.
2
catalytic features of the homogeneous system were successfully
embedded onto the silica surface. Furthermore, a small number
of non-heme iron-catalyzed epoxidation catalysts have recently
been prepared. For example, Jacobsen reported an Fe-mep cat-
alyst (mep = N,N¢-dimethyl-N,N¢-bis(2-pyridylmethyl)ethane-
2
1
1
,2-diamine) and Stack described an oxide-bridged bimetallic
2
22
iron catalyst bearing phenanthroline ligands. Both of these
catalysts employ acetic acid, which in the case of Jacobsen’s
system is proposed to give the active iron species, whereas in
Stack’s system it is used to generate peracetic acid as the active
3
The use of stoichiometric oxidants that generate significant
waste, especially toxic metal residues such as chromates and
permanganates is being discouraged in favour of catalytic
processes. For economical and ecological reasons, molecular
oxidant upon reaction with H
that a combination of FeCl
·6H
,6-dicarboxylic acid (H pydic) and an organic base catalyzed
the epoxidation of olefins with H During
2
O
2
. Recently, Beller demonstrated
3
2
O, with and without pyridine-
2
2
4
23–27
oxygen and hydrogen peroxide are the preferred oxidants.
2
O
2
in good yield.
Hydrogen peroxide is generally easier to handle, cheap and
produces water as a by-product. Thus, the combination of
these studies, it was shown that 5-chloro-1-methylimidazole was
capable of high yielding epoxidations of aromatic alkenes (e.g.
5
hydrogen peroxide with a non-toxic and inexpensive metal
source constitutes an ideal system for epoxidation reactions,
styrenes and stilbenes) without the use of H
2
pydic, but was
unsuccessful for aliphatic alkenes. A combination of H pydic
with bulky imidazole bases was required for epoxidation of a
25
2
6–13
especially in liquid phase processes in industry.
the use of H in combination with catalytic amounts of first
row late transition metals such as Fe or Mn is desirable.
The use of H in combination with simple non-heme
complexes is limited, due to the vigorous
Therefore,
26
2
O
2
broader range of substrates.
We are interested in pursuing the reactivity of iron complexes
supported by amine-bis(phenolate) ligands for catalytic organic
synthesis. For example, we have recently reported iron(III)
complexes of tridentate and tetradentate amine-bis(phenolate)
ligands as effective catalysts for C–C cross coupling between aryl
2
O
2
13
14,15
Mn or Fe
decomposition of H
16–18
2
O
2
in the presence of these metals.
How-
28–30
Grignard reagents and alkyl halides.
These Fe(III) complexes
Department of Chemistry, Memorial University of Newfoundland, St.
John’s, Newfoundland, A1B 3X7, Canada. E-mail: ckozak@mun.ca;
Fax: +1-709-864-3702; Tel: +1-709-864-8082
are inexpensive and possess low environmental toxicity, and
are therefore interesting candidates for further study of their
reactivity. Herein we report the use of simple iron(III) chloride
salts in the presence of readily available organic N-containing
†
Electronic supplementary information (ESI) available: Characteriza-
tion data (GC-MS) for epoxide products. See DOI: 10.1039/c0gc00943a
1
230 | Green Chem., 2011, 13, 1230–1237
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bases, as well as the influence of amine-bis(phenol) ligands, for
catalytic epoxidation of internal and terminal, aromatic and
Table 2 Epoxidation of trans-stilbene in the presence of different iron
a
sources
aliphatic olefins using H
2
2
O .
Results and discussion
Imidazole plays a crucial role in biological systems especially
Conv. Yield Select.
31
in metalloenzymes. It is also used as an additive for epox-
Entry Iron source
Additive
(%)
(%)
(%)
32
idation systems with iron porphyrin complexes. Inspired by
the recent results obtained by the group of Beller, preliminary
screening started with using a mixture of appropriate amounts
1
2
3
4
5
6
7
8
9
1
1
FeCl
FeCl
3
·6H
2
O
1-Methylimidazole 93
1-Methylimidazole 100
90
90
0
0
0
97
90
0
0
0
3
FeBr
Fe(NO
Fe(acac)
FeCl
Fe(BF
Fe(ClO
3
1-Methylimidazole
1-Methylimidazole
1-Methylimidazole
0
0
0
of FeCl
Table 1). Trans-stilbene was chosen as the substrate for the
epoxidation process using H as oxidant. A solution of H
3
·6H
2
O and 1-methylimidazole in a number of solvents
3
)
3
·9H
2
O
(
3
2
1-Methylimidazole 88
1-Methylimidazole 19
1-Methylimidazole 16
1-Methylimidazole 19
49
9
16
10
18
9
55
44
100
54
94
76
2
O
2
2
O
2
4
)
4
2
·6H
2
O
O
-
1
was added over a period of 1 h at 1 mL h using a syringe
pump. In the first instance, tert-amyl alcohol was used as the
solvent due to its use in previously reported metal-catalyzed
)
2
·H
2
Fe(CH
Fe(CH
Fe O
2 3
3
COO)
COO)
2
0
1
3
2
Acetic acid
20
1-Methylimidazole 12
33,34
epoxidation reactions.
Using these conditions, 31% trans-
a
stilbene oxide was obtained after stirring the reaction mixture
at room temperature for 19 h (Table 1, entry 1). Beller and co-
workers observed 18% yield of trans-stilbene oxide in 1 h under
Reaction conditions: To a 45 mL reaction tube of a Radleys Carousel
TM
Reactor , Fe salt (0.025 mmol), additive (0.05 mmol), acetone (9 mL),
trans-stilbene (0.5 mmol), and dodecane (GC internal standard, 50 mL)
were added in sequence at r.t. in air. The mixture was stirred and a
solution of 30% H O (170 mL, 1.5 mmol) in acetone (830 mL) was
26,35
these reaction conditions,
however, they went on to show
2
2
added over a period of 1 h by a syringe pump. The reaction mixture was
heated to 62 C for 18–21 h. Conversion and yields were determined
by GC-MS and NMR analysis. Selectivity refers to the ratio of yield to
conversion in percentage.
trans-stilbene oxide formation was improved to 80% using 5-
◦
25
chloro-1-methylimidazole instead of 1-methylimidazole. The
use of non-halogenated organic additives is desirable from
an environmental perspective, but also in terms of cost 1-
methylimidazole is approximately 400 times less expensive
36
than 5-chloro-1-methylimidazole. Therefore, we sought a way
to improve the yield of epoxide using the inexpensive 1-
methylimidazole as additive. In our studies, only tert-amyl
alcohol, acetonitrile and acetone gave significant conversions
with excellent selectivity, with acetone giving the best result
towards the epoxidation of trans-stilbene (entry 6) at room
temperature, giving 40% yield of stilbene oxide. Heating the
reaction to 62 C for 19 h, however, increased the yield to 90%
with 97% selectivity showing modestly elevated temperatures
are required to obtain a significant increase in both conversion
of starting material and yield of desired epoxide product. In the
absence of either FeCl
no conversion of alkene to epoxide was observed.
3
·6H
2
O or 1-methylimidazole compounds,
Having observed such promising results when mixtures of
Fe(III), 1-methylimidazole and H
2
2
O were heated with trans-
stilbene, we examined the influence of the iron salt on epoxida-
tion in acetone (Table 2). Iron(III) chloride hexahydrate (Strem
Chemicals, 97+%) showed excellent conversion and high yield
of corresponding epoxide (entry 1 shows the average of three
◦
runs). Similar results were obtained by using anhydrous FeCl
3
a
Table 1 Epoxidation of trans-stilbene in different solvents
(Sigma Aldrich, 97%), which demonstrates reproducibility when
different sources of the salt are used (entry 2). Surprisingly,
other Fe(III) salts did not show any catalytic epoxidation of
trans-stilbene (entries 3 to 5), whereas iron(II) chloride gave
high conversion of trans-stilbene, but the yield of epoxide was
much lower than for iron(III) chloride (entry 6). The nature
of the counter ion appears significant, since Fe(II) salts with
different anions (i.e. tetrafluoroborate, perchlorate and acetate)
Entry
Solvent
Conv. (%)
Yield (%)
1
2
3
4
5
6
tert-Amyl alcohol 31
31
0
0
(entries 7 to 9) showed low conversion and yield. In the case of
Isopropyl alcohol
Water
Dichloromethane
Acetonitrile
Acetone
0
iron(II) acetate, using acetic acid instead of 1-methylimidazole
did not improve conversion, but selectivity was increased (entry
0
0
35
40
0
35
40
90
10). Interestingly, even iron(III) oxide showed some catalytic
b
b
activity toward epoxidation trans-stilbene (entry 11). What this
study showed was the apparent importance of the chloride
ion to epoxidation catalysis under these conditions. Therefore,
9
3
a
Reaction conditions: To
a
50 mL Schlenk tube, FeCl
3
·6H
2
O
(
0.025 mmol), 1-methylimidazole (0.05 mmol), solvent (9 mL), trans-
other first-row transition metal chlorides (i.e. MnCl
CoCl O, NiCl ·6H O and CuCl ) were examined using
·6H
these reaction conditions. Slow addition of H O solutions to
2
·4H
2
O,
stilbene (0.5 mmol), and dodecane (GC internal standard, 100 mL) were
added in sequence at 25 C in air. The mixture was stirred and a solution
◦
2
2
2
2
2
2 2
of 30% H O (170 mL, 1.5 mmol) in solvent (830 mL) was added over
2
2
a period of 1 h using a syringe pump. The reaction mixture was stirred
acetone solutions containing 1-methylimidazole, trans-stilbene
and 5 mol% of metal chloride followed by heating showed no
conversion of the alkene to oxidized products.
◦
at 25 C for 18–21 h. Conversion and yields were determined by GC
b
◦
analysis. The reaction mixture was heated for 20 h at 62 C.
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a
Next, the effect of different additives in combination with
FeCl O was studied for the epoxidation of trans-stilbene.
Table 3 Epoxidation of trans-stilbene in presence of different additives
3
·6H
2
The additives were selected to include either acidic or basic
functionality that can easily coordinate with Fe(III). Among the
additives, carboxylates can bridge metal centers and activated
carbonyl groups can easily react with peroxide to enhance
Entry Additive
Conv. (%) Yield (%) Selectivity (%)
5
the epoxidation process. However, we obtained a relatively
low yield of epoxide using acetic acid under the experimental
conditions used (Table 3, entry 1), and a number of by-
products were observed by GC-MS (see ESI†). In the presence
of diphenylamine (entry 2), no significant formation of trans-
stilbene oxide was observed. This might be due to the bulkiness
of the phenyl groups, which hinder the reactivity at the iron
centre. However, in the case of N-phenylpyrrole conversion was
1
2
CH CO H
51
44
16
0
30
0
3
2
3
4
53
50
37
30
100
60
5
3% but yield for epoxide product was 37% (entry 3). In these
cases (entries 1–3), the main by-products were benzaldehyde and
,2-diphenylethane-1,2-diol. These by-products were observed
1
5
6
93
90
18
97
91
b
b
c
b
1
9
in reactions where low yields of trans-stilbene oxide are obtained.
Employing 3,5-dimethylpyrazole (entry 4) showed relatively low
yield and conversion toward trans-stilbene epoxidation. As men-
67
52
78
b
b
b
7
4
61c
tioned above, using 1-methylimidazole with FeCl
3
·6H
2
O gave
c
c
1
00
66
66
an excellent yield (90%) and selectivity (97%) for epoxidation
of trans-stilbene, but heating was required to achieve optimum
results (entry 5). We therefore investigated other N- and C-
substituted imidazoles to see their effect on catalytic activity,
but none proved as effective as 1-methylimidazole. Using the 2-
position substituted 1,2-dimethylimidazole, 52% yield with 67%
conversion were obtained for trans-stilbene epoxidation (entry
7
8
9
56
40
65
71c
c
c
1
00
65
c
c
36
33
92
6
). Increasing the amount of H
2
O
2
to 3.0 mmol (a six-fold excess
versus olefin substrate) but maintaining the Fe(III) loading at
b
b
b
5
1
mol% with respect to trans-stilbene increased conversion to
00%, but the yield increased only slightly to 66%. This is a
5
5
87
vast improvement compared to a previous report where iron-
catalyzed epoxidation in the presence of 1,2-dimethylimidazole
showed very poor conversion (7%) and yield (4%) of epoxide.
26
a
Reaction conditions: To a 45 mL reaction tube of a Radleys Carousel
TM
Using only C-substituted 2-ethyl-4-methyl imidazole showed
relatively low yield (40%) and conversion (56%) (entry 7).
Reactor , FeCl
(
5
3
·6H
2
O (0.025 mmol), additive (0.05 mmol), acetone
9 mL), trans-stilbene (0.5 mmol), and dodecane (GC internal standard,
◦
0 mL) were added in sequence at 25 C in air. The mixture was stirred
But again, increasing the amount of H
2
2
O to 3.0 mmol from
2 2
and a solution of 30% H O (170 mL, 1.5 mmol) in acetone (830 mL)
1
.5 mmol improved the yield to 65% with a 100% conversion. The
was added over a period of 1 h using a syringe pump. The reaction
◦
mixture was heated to 62 C for 18–21 h. Conversion and yields were
bulkier 2-phenyl-4-methylimidazole only produced 33% trans-
stilbene oxide with 36% conversion (entry 8) when oxidized by
determined by GC-MS and NMR analysis. Selectivity refers to the ratio
b
26
of yield to conversion in percentage. Previously reported conditions:
O and 10 mol% imidazole
3
.0 equiv. of H
2
O
2
.
0
.5 mmol trans-stilbene, 5 mol% FeCl
3
·6H
2
Our results using 2-substituted imidazoles show considerably
derivative, tert-amyl alcohol (9 mL), 0.44 mmol dodecane as internal
standard were added in sequence at room temperature in air. To this
higher activity than in previous reports where it was found
that the substitution pattern of the imidazole was critically
important for obtaining significant catalytic activity towards the
epoxidation of olefins. Specifically, the presence of alkyl groups
in the 2-position of the imidazole was previously found to be
detrimental to the epoxidation of trans-stilbene compared to
mixture a solution of 30% H
830 mL) was added over 1 h at room temperature by syringe pump.
Conversion and yield were determined by GC analysis. Selectivity refers
2 2
O (170 mL, 1.5 mmol) in tert-amyl alcohol
(
c
to the chemoselectivity of epoxide from olefin. 30% H
.0 mmol) in acetone (1660 mL) was added over a period of 2 h using a
syringe pump.
2 2
O (340 mL,
3
26
those having H-functionalized 2-positions (entries 6 and 9).
The decreased reactivity of the 2-substituted imidazoles was
proposed to result from the involvement of a carbene-type
“abnormal” carbenes (i.e. bonded to the metal through the 5-
position) are still possible. Also, while intramolecular hydrogen
37
38
ligand in the catalytic cycle or hydrogen bonding between
the proton in the 2-position of a coordinated imidazole and
an iron hydroperoxo species. We, however, have found that
using imidazoles bearing alkyl groups in the 2-position did not
necessarily result in poor yields of epoxide under our conditions
bonding may not be likely due to the position of the hydrogen-
bond donor relative to the basic nitrogen atom of the imidazole
ring, intermolecular hydrogen bonding may still be achieved.
Regardless, by obtaining a moderate yield of epoxide using
2-position substituted imidazoles suggests other mechanistic
pathways are possible using these reaction conditions.
(
entries 6, 7 and 8). This does not necessarily invalidate the
involvement of a carbene-type interaction of the imidazole since
1
232 | Green Chem., 2011, 13, 1230–1237
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a
Various other substrates were studied for epoxidation
catalyzed by FeCl O (5 mol%) and 1-methylimidazole
·6H
10 mol%) and the results are given in Table 4. As observed
in Table 3, entries 6 and 7, use of six-fold excess of H led
Table 4 Olefinic substrates screened for epoxidation
3
2
(
2
O
2
to improved yields, therefore these conditions were employed
for further reactions. Thus, the conversion of trans-stilbene can
be improved to 100% with a 100% yield of epoxide product
Entry Substrate
1
Conv. (%) Yield (%) Select. (%)
◦
upon heating the reaction to 62 C for 21 h (Table 4, entry
100
100
100
1
). This catalytic system is applicable for both aliphatic and
aromatic systems and mono-, di- and tri- substituted olefins
can be epoxidized in good-to-excellent yields and selectivity.
The epoxidation of cis-stilbene is typically low yielding and
the best result reported in the literature to date is 34% con-
2
66
64
76
97
87
b
b
b
8
7
25
version with 24% yield of epoxide. Using the FeCl
methylimidazole system in acetone gave better conversion (66%)
3
·6H
2
O/1-
3
4
100
91
64
91
64
and yield (64%), however, cis-stilbene was converted to trans-
1
stilbene oxide (entry 2) as determined by H NMR. Heating
the reaction for 48 rather than 20 h improved the conversion to
100
8
7% with 76% yield. The conversion of trans-b-methyl styrene is
quantitive; however, the yield of the epoxide product is moderate
(
(
entry 3). Under the same conditions, trisubstituted acyclic
entry 4) and cyclic alkenes (entry 5) can also be converted to
5
6
100
84
95
58
95
69
epoxides in excellent yields. Terminal olefins (entries 6 to 8) are
a particularly challenging class of substrate for epoxidation due
to their relatively electron deficient nature.
5,39,40
c
Halo-substituted
8
styrenes (entries 6 to 8) showed moderate conversion and
selectivity for epoxidation, even for the ortho-substituted 2-
chlorostyrene. The main by-product in these cases was halogen-
substituted acetophenone (see ESI†). It appears that both steric
and electronic effects limit olefin conversion. For example, trans-
stilbene conversion was 100% (entry 1) whereas cis-stilbene
conversion was 66% (entry 2) under the same condition, likely
because of steric constraints caused by cis-oriented phenyl
groups. Also the moderately sterically encumbered trans-a-
methyl stilbene gave a conversion of 91% (entry 4) which was
between that observed for the trans and cis-stilbene conversions.
Regarding electronic effects, halo-substituted electron-deficient
olefins (entries 6–8) exhibited conversions of 80–86%, which
were lower thanunsubstituted terminal olefin like trans-b-methyl
styrene (100%) (entry 3). Cyclic aliphatic alkenes were converted
to epoxides with varying yields (entries 9 to 11). Limonene
oxide has been employed as a feedstock for polycarbonate
7
8
86
80
69
80
81
c
1
5
65
15
c
9
95
65
68
10
11
79
69
95
87
95
100
41
synthesis and since it can be obtained from renewable sources
citrus fruit peels), a catalytic, green method of epoxidation is
(
desirable. Catalytic limonene epoxidation has been previously
1
1
2
3
96
87
66
72
63
83
achieved by using dioxomolybdenum complexes with t-BuOOH
◦
heated to 55 C for 24 h obtaining 95% epoxide product with
42
1
00% selectivity. Iron has also showed catalytic limonene
epoxidation with H as the oxidant but the yields were
2
O
2
typically much lower. For example, iron polynitroporphyrin
complexes produced a 24% yield of limonene oxide in a 1 : 1
43
II
2+
mixture of CH
2
Cl
2
and MeCN. Also, [Fe (bpy) solvent] gave
2
a
Reaction conditions: To a 45 mL reaction tube of a Radleys Carousel
4
6% limonene oxide in MeCN after 24 h, but side products such
TM
Reactor , FeCl
3
·6H
2
O (0.025 mmol), 1-methylimidazole (0.05 mmol),
44
as carvone and carveol were also produced. Our catalyst system
acetone (9 mL), olefin (0.5 mmol), and dodecane (GC internal standard,
5
and a solution of 30% H O (340 mL, 3.0 mmol) in acetone (1660 mL)
2 2
was added over a period of 2 h using a syringe pump and heated to
◦
0 mL) were added in sequence at 25 C in air. The mixture was stirred
was investigated for epoxidation of both (+) and (-) limonene
(
(
entries 12 and 13) and high conversions (~ 90%) with good yields
~ 69%) were obtained. To our knowledge, these are the highest
◦
6
2
C for 19–21 h. Conversion and yield were determined by GC-MS
yields of limonene oxide obtained by Fe-catalyzed epoxidation.
Unfortunately, no stereocontrol is observed as both isomers of
and NMR analysis. Selectivity refers to the ratio of yield to conversion
in percentage. Heated to 62 C for 48 h. Yield of ketone by-product.
b
◦
c
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Table 5 Screening of Fe(III) complexes with tetradentate amine-
Table 6 Epoxidation of trans-stilbene using tridentate amine-
a
a
bis(phenol) ligands
bis(phenol) ligands with FeCl
3
·6H
2
O
Entry Complex/Proligand Additive
Conv. (%) Yield (%)
Entry
Ligand
Conv. (%)
Yield (%)
Select. (%)
b
b
1
2
3
4
5
6
7
1
1-Methylimidazole 36
1-Methylimidazole 30
36
26
24
29
0
1
2
3
4
5
6
H
H
H
H
H
H
2
2
2
2
2
2
L4
L5
L6
L7
L8
L9
75
67
57
88
59
62
64
51
34
61
49
56
85
76
60
69
83
90
H
H
H
H
H
H
2
2
2
2
2
2
L1
L1
L2
L3
L3
L3
Imidazole
27
1-Methylimidazole 33
Triethylamine
Pyrolidine
Acetic acid
0
0
0
0
0
a
Reaction conditions: To a 45 mL reaction tube of a Radleys
a
TM
Reaction conditions: To
a
25 mL Schlenk tube, FeCl
3
·6H
2
O
Carousel Reactor , FeCl
3
·6H
2
O (0.025 mmol), ligand (0.025 mmol), 1-
(
0.025 mmol), ligand (0.025 mmol, if used), additive (0.05 mmol), tert-
methylimidazole (0.05 mmol), acetone (9 mL), trans-stilbene (0.5 mmol),
amyl alcohol (9 mL), trans-stilbene (0.5 mmol), and dodecane (GC
and dodecane (GC internal standard, 50 mL) were added in sequence
◦
◦
internal standard, 100 mL) were added in sequence at 25 C in air. The
at 25 C in air. The mixture was stirred and a solution of 30% H
2
O
2
mixture was stirred and a solution of 30% H
2
O
2
(170 mL, 1.5 mmol)
(170 mL, 1.5 mmol) in acetone (830 mL) was added over a period of 1 h
using syringe pump and heated at 62 C for 19–21 h. Conversion and
yield were determined by GC-MS and NMR analysis. Selectivity refers
to the ratio of yield to conversion in percentage.
◦
in tert-amyl alcohol (830 mL) was added over a period of 1 h using a
◦
syringe pump and stirred at 25 C for 19 h. Conversion and yield were
b
determined by GC-MS analysis. Acetone used as solvent.
limonene are converted to mixtures of the cis and trans epoxide
products.
amount of FeCl
3
·6H
2
O to solutions of tetradentate amine-
bis(phenol) proligands, H
2
L1, H
2
L2 or H L3 in tert-amyl alco-
2
The use of 2,6-pyridinedicarboxylic acid as ancillary ligand
in combination with simple amines for Fe-catalyzed epoxi-
◦
hol at 25 C. To these mixtures were added the basic or acidic co-
47
catalysts. These conditions are generally found to give at least
23,45,46
dation of olefins by H
2
O
2
has been reported.
Use of
24
modest yields in other iron-catalyzed epoxidations. However,
only the use of imidazole bases gave any epoxide product (yields
this ligand was thought to be crucial for obtaining high
yields of epoxide products, but it was later shown that by
using sterically demanding imidazole ligands the need for
~
30%) (entries 2–4) and no significant influence was observed by
varying the ligand. No yields of epoxide products were obtained
26
2
,6-pyridinedicarboxylic acid was alleviated. Our group has
in the presence of triethylamine, pyrolidine or acetic acid with
reported the catalytic activity of Fe(III) complexes bearing
tetradentate and tridentate amine-bis(phenolate) ligands to-
◦
H
(
2
L3 and FeCl
entries 5–7).
Since these tetradentate ligands did not show promise as
3
·6H
2
O even after prolonged stirring at 25 C
28–30
wards C–C cross-coupling reactions.
There is a structural
similarity between 2,6-pyridinedicarboxylic acid and amine-
bis(phenol) ligands (Fig. 1), namely they both possess acidic
ancillary ligands in Fe-catalyzed epoxidation of trans-stilbene,
the less coordinatively demanding tridentate amine-bis(phenol)
–
OH sites and neutral N-donors. Therefore, Fe(III) amine-
ligands (abbreviated H
methylimidazole as co-catalyst. An aqueous solution of H
was diluted in acetone and added to a mixture of FeCl
·6H
[O N], 1-methylimidazole and trans-stilbene in acetone. Also,
2
[O
2
N]) were studied (Fig. 2) using 1-
bis(phenolate) complexes were investigated for catalytic epox-
idation of olefins to see whether any enhancement of reactivity
could be obtained. However, using a combination of pre-
made Fe(III) amine-bis(phenolate) complex 1 (the iron chloride
complex of L3, shown in Fig. 1) and 1-methylimidazole gave
2
O
2
3
2
O,
H
2
2
since the reactions in Table 5 gave unimpressive yields of epoxide
at room temperature, the reactions given in Table 6 were heated
30% yield of trans-stilbene oxide in acetone (Table 5, entry 1).
◦
to 62 C for 20 h. Under these conditions, all the systems
studied exhibited catalytic activity toward the epoxidation of
Fig. 1 Iron complex 1 and tetradentate amine-bis(phenol) proligands
used in this study.
Next, the effect of in situ iron complexation by amine-
bis(phenol) ligands, H
2
L1, H
2
L2 and H
2
L3 was studied. Screen-
ing of ligand effects was conducted by adding the appropriate
Fig. 2 Tridentate amine-bis(phenol) ligands used in this study.
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1
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trans-stilbene, but unlike for the tetradentate ligands, a slight
ligand effect was observed. In the presence of ligands with
electron donating and sterically bulky tert-butyl groups in the
ortho- and para-positions relative to the phenol oxygen atom
and yield are obtained after 20 h, whereas the reaction is
complete (100% conversion and yield) within 21 h when no
amine-bis(phenolate) ligand is present (Fig. 3B).
Because of the lengths of time involved in these epoxidation
(
6
Table 6, entries 1, 2 and 4), trans-stilbene oxide formed in 51–
4% yield with 69–85% selectivity. The lowest yield was attained
using proligand H L6, which possesses electron-withdrawing
fluoro groups (entry 3). Highest selectivity (90%) was achieved
by using the more bulky tert-amyl-substituted ligand H L9
entry 6) with a 56% overall yield of trans-stilbene oxide.
reactions, it is reasonable to query whether any H
2
O is present
2
in the reaction after this time period. In other words, is all the
peroxide consumed early in the reaction or perhaps converted
to another oxidant? We therefore performed titrations of several
reaction mixtures after 21 h to quantify any unreacted H
may remain. Under the conditions employed in Table 4, entry 1,
titration of the mixture after 21 h reveals that 5.81% of the added
2
2
2
O that
2
(
Nonetheless, what is apparent is that the presence of these
ligands in the catalytic system actually lowers the epoxidation
H
2
O
2
remains. Using 170 mL of H
entry 1, 2.81% of the added H remained. The consumption of
has some limiting effect of the olefin conversion. Namely,
as shown in Table 2, entry 1, 93% conversion of trans-stilbene was
obtained after using 170 mL of H whereas 100% conversion of
trans-stilbene was obtained after using 340 mL of H (Table 4,
entry 1). When 170 mL of H was added to Fe(acac) as the iron
source instead of FeCl O (Table 2, entry 5), the remaining
·6H
was 2.46%, but no epoxidation was observed. Therefore,
it appears the iron catalyst precursors do not influence the rate
of consumption of H , but they are vital to the epoxidation
process itself. The solvent used also shows some effect on the
consumption of H because 9.85% of the H remains when
acetonitrile was used as solvent (Table 1, entry 5). During the re-
action, H may be converted to other oxidants, such as HOCl,
and investigations into this are underway. Also, a very recent re-
port by Beller and co-workers shows FeCl O in the presence
·6H
of a b-keto ester (ethyl-2-oxocyclopentanecarboxylate) epoxi-
2
O
2
, as performed in Table 2,
activity compared to just FeCl
acetone under heating.
3
·6H
2
O and 1-methylimidazole in
2
O
2
H
2
O
2
During our studies, FeCl
3
·6H O and 1-methylimidazole in
2
acetone were found to be the best catalytic system for olefin
epoxidation by dilute H . However, the reactions proceeded
2
O
2
2
O
2
2
O
2
slowly and required heating for several hours to achieve high
yield of epoxide product. Preliminary kinetic studies of the
catalyst system were performed by monitoring two epoxidation
reactions in the presence and absence of amine-bis(phenol)
2
O
2
3
3
2
H
2
O
2
proligand, H
2
L7. Plots of conversion and yield versus time
2
O
2
are given in Fig. 3. From these observations, it was found
that the rate of epoxide formation decreases over time, but
the epoxidation continues to proceed over the duration of the
experiments. As shown in Fig. 3A, the presence of H
slows the epoxidation of trans-stilbene and only 79% conversion
2
O
2
2
O
2
2
L7 actually
2
O
2
3
2
48
dizes olefins using air as the oxidant and no H
2
2
O was required.
Because our reactions were also conducted under aerobic con-
ditions, we questioned whether it was the presence of air rather
than peroxide that led to epoxidation. Performing the reaction
in air as described in Table 2, entry 1 or Table 4, entry 1, without
the addition of H
2
2
O showed no formation of epoxide product.
The exact nature of the catalytic species is unknown at
this time, however, crystalline material was obtained from a
solution of FeCl
acetone and X-ray diffraction studies of this product unsurpris-
ingly revealed it to be the octahedral complex, trichlorotris(1-
methylimidazole)iron(III). Generally, high-valent iron-oxo
compounds act as the catalytic species for the oxygen activating
non-heme iron enzymes. The reaction of iron porphyrin
complexes with H forms high-valent iron(IV) oxo porphyrin
cation radical intermediates, [(Porp) Fe
3
·6H
2
O and 2 equiv. of 1-methylimidazole in
49
50
2
O
2
+
∑
IV
O], which are gen-
32
erated via O–O bond heterolysis. In our catalyst system, a
high-valent iron-oxo species may also be the active catalyst. Of
course it cannot be ignored that the combination of acetone and
H
2
O
2
under acidic conditions can also result in the formation
of explosive cyclic peroxides, and therefore this solvent may
not be suitable for industrial applications involving H
2
2
O .
Nonetheless, no accumulation of alkylperoxides was observed
when performed on a laboratory scale. Indeed, the formation
of 2-hydroperoxy-2-hydroxypropane (hphp) has been proposed
as a reason for decreased decomposition of the oxidant in the
1
presence of a metal catalyst. Thus, due to the dilution of the
H
2
O
2
solution in acetone, the epoxidation reaction is favoured
over oxidant decomposition. Therefore, hphp can be considered
either an “oxidant reservoir” which gradually releases H
Fig. 3 Monitoring the progress of epoxidation of trans-stilbene in the
presence (A) and absence of amine-bis(phenol) ligand H L7 (B).
2
2
O
2
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maintaining a low oxidant concentration or it may directly be
involved in the epoxidation pathway itself. Further mechanistic
studies are ongoing in our laboratory.
prepared by careful removal of solvent and dissolving the residue
in CDCl .
3
Method for determination of H
2
O
2
concentration
Conclusions
Determination of remaining H O was performed by cooling
the epoxidation reactions to room temperature and removing
any precipitated material by filtration through glass filter paper.
2
2
We have demonstrated that simple epoxidation of both ter-
minal and substituted (both endo- and exocyclic) olefins
can be achieved using low concentrations of FeCl
The filtered solution was acidified using 3 M H
for reactions using 170 mL 30% H or 1.2 mL for reactions
using 340 mL 30% H ). The acidic solution was titrated with
2
SO
4
(0.8 mL
3
·6H
2
O
2
O
2
and 1-methylimidazole in acetone. The use of acetone as a
solvent presents a potential advantage over other solvents
typically employed, namely toxic acetonitrile, carcinogenic
dichloromethane, and costly tert-butyl or tert-amyl alcohols.
Also, this catalytic system employs the simple and readily
available 1-methylimidazole as additive/co-catalyst, which is
considerably less expensive than other imidazole-containing co-
catalysts reported to date.
2
O
2
standardized 0.10 M KMnO solution.
4
Acknowledgements
C. M. K. thanks Memorial University of Newfoundland, the
Natural Sciences and Engineering Research Council (NSERC)
of Canada, the Canada Foundation for Innovation (CFI) and
the Government of Newfoundland and Labrador for funding.
We are grateful to Prof. Francesca M. Kerton for use of the GC-
MS instrument, acquired through a CFI Leaders Opportunity
Fund Award. K.H. thanks the Memorial University School of
Graduate Studies for a Merit Award.
Experimental
General experimental conditions
Unless otherwise stated, all manipulations were performed
in air by using a Radleys 12 Carousel Reactor. Organic
reagents, solvents and alkene substrates were purchased from
either Sigma–Aldrich or Alfa Aesar and used without further
Notes and references
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3
·6H
2
O was purchased from Strem Chem-
2
2
O
2
from
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9,52
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