1

PERKIN
Selenium catalysed oxidations with aqueous hydrogen peroxide.
Part I: epoxidation reactions in homogeneous solution

Gerd-Jan ten Brink, Bruno C. M. Fernandes, Michiel C. A. van Vliet, Isabel W. C. E. Arends
and Roger A. Sheldon *

Laboratory for Organic Chemistry and Catalysis, Delft University of Technology,

Julianalaan 136, 2628 BL Delft, The Netherlands. E-mail: [email protected];
fax: ⫹31-15-2781415; tel: ⫹31-15-2782683

Received (in Cambridge, UK) 11th October 2000, Accepted 7th December 2000
First published as an Advance Article on the web 10th January 2001

Several diselenides were synthesised and tested for catalytic activity in epoxidation reactions with aqueous hydrogen
peroxide. Bis[3,5-bis(trifluoromethyl)phenyl] diselenide forms the corresponding 3,5-bis(trifluoromethyl)benzene
seleninic acid (L. Syper and J. Mlochowski, Tetrahedron, 1987, 43, 207.) in situ, which is a highly reactive and selective
catalyst for the epoxidation of olefins in 2,2,2-trifluoroethanol. This is the first selenium compound that effectively
(substrate to catalyst molar ratio s/c = 200) catalyses the formation of sensitive epoxides in nearly quantitative yields.

Introduction
Olefin epoxidation is a key transformation in organic synthesis
both on a laboratory and an industrial scale.2,3 The method of
choice—in fine chemicals production—is usually the Prilezhaev
reaction of olefins with stoichiometric amounts of percarb-
oxylic acids, such as peracetic and m-chloroperbenzoic acid.4
Major disadvantages of this method are the relatively high cost
of peracids, the need for large amounts of (buffered) organic
solvents and the co-production of the corresponding carboxylic
acid, which has to be separated from the product. Moreover,
increasingly stringent regulation of the transport, storage and
handling of peracetic acid are making its use prohibitive. Con-
sequently, effective catalytic methods for epoxidation with
aqueous hydrogen peroxide are actively being sought. Aqueous
hydrogen peroxide is inexpensive, relatively safe and easy to
handle and produces water as the sole co-product.
Several systems have been reported in the literature, based on
tungstate,5,6 methyl rhenium trioxide (MTO),7 manganese tri- Fig. 1 Catalytic epoxidation with arylseleninic acid–hydrogen
azacyclononane complexes 8 and the heterogeneous titanium peroxide systems.
silicalite (a hydrophobic molecular sieve),9 but the search for
effective, stable catalysts with broad scope continues. Organo- Solvent effects
metallic compounds of main group elements, notably arsenic 10
and selenium 11 are also known to catalyse epoxidations. Peroxy- The choice of solvent for epoxidation reactions with hydrogen
seleninic acids were first used as stoichiometric oxidants,12 but peroxide is limited. A solvent should preferably be polar,
following the discovery, by Sharpless,13 that tert-butyl hydro- non-coordinating, non-basic and inert under the oxidising con-
peroxide can be used in conjunction with catalytic amounts, the ditions. This leaves only a few possibilities e.g. chlorinated
method gained interest.14 Further improvements came with hydrocarbons, 2,2,2-trifluoroethanol 18 and sulfolane (1,1-
the use of hydrogen peroxide instead of tert-BuOOH as the dioxothiole). A water-immiscible solvent is often preferred, to
oxidant, heterogenisation 15,16 and functionalisation of the minimise hydrolysis of the epoxides,6 but with aqueous hydro-
aromatic ring of the selenium catalyst with electron with- gen peroxide this can cause problems with mass transfer.5,19
drawing nitro-substituents (Fig. 1).17 However, the reaction Chlorinated hydrocarbons are less interesting because of
conditions (≥5 mol% catalyst, reaction times up to 12 h) and environmental issues associated with their use.20
results (selective epoxidation of activated olefins only) left room In an initial solvent screening (Table 1) the epoxidation of
for improvement.16,17 This prompted us to study the effect of cyclohexene in the presence of 0.5 mol% of bis[3,5-bis(trifluoro-
the nature and position of substituents in the aromatic ring of methyl)phenyl] diselenide (1) was studied since this olefin gives
the selenium catalysts and solvent and base effects to ascertain information regarding reactivity and selectivity. The best results
whether further improvement was possible. were obtained in 2,2,2-trifluoroethanol, dichloromethane and
sulfolane. The advantage of 2,2,2-trifluoroethanol as a solvent
in epoxidations has been known for some time.21 It combines
Results the prerequisites of a good solvent (polar, non-basic, non-
The structures of the diselenides used are depicted in Fig. 2. coordinating, non-oxidisable) with a very high rate of epoxid-
Under the reaction conditions the diselenides are oxidised by ation compared to the rate of solvolysis. Consequently, the
H2O2 to give the corresponding aryl seleninic acids (ArSe(O)- complete miscibility with aqueous hydrogen peroxide, which
OH) which are the true catalysts.1 eliminates mass transfer limitations, does not pose a threat to

224 J. Chem. Soc., Perkin Trans. 1, 2001, 224–228 DOI: 10.1039/b008198l

This journal is © The Royal Society of Chemistry 2001
Table 1 Solvent screening for cyclohexene epoxidation 1 a Table 2 Effect of base on cyclohexene epoxidation with 1 a

Solvent TOF0 b Yield (%) c Selectivity (%) d Diol

Yield Selectivity formation
b
2,2,2-Trifluoroethanol 250 88 90 Base pKa TOF0 (%) c (%) d (%)
Dichloromethane 40 35 90
1,2-Dichloroethane 34 21 68 None — 300 80 85 ~3
Nitromethane 27 19 69 Pyrazole 2.5 350 75 96 ~3
Sulfolane e 21 14 95 NaOAc 4.77 420 98 99 <1
α,α,α-Trifluorotoluene 12 7 49 Na2HPO4 7.21 470 82 91 0
a a
Conditions: 0.5 mol% 1, 2 mmol cyclohexene, 4 mmol 60% H2O2, 1 M Conditions: 0.25 mol% 1, 2 mmol cyclohexene, 0.2 mol% base, 4 mmol
solutions, T = 20 ⬚C, t = 1 h. b TOF0 = initial rate in mmol product 60% H2O2, 1 M solutions, T = 20 ⬚C, t = 1 h; pKa denotes the pKa of
(mmol catalyst)⫺1 h⫺1. c GC-yield on epoxide. d Selectivity = mmol the conjugated acid. b TOF0 = initial rate in mmol product (mmol
epoxide (mmol converted olefin)⫺1. e Reaction carried out at 30 ⬚C (mp catalyst)⫺1 h⫺1. c GC-yield on epoxide. d Selectivity = mmol epoxide
sulfolane = 27 ⬚C). (mmol converted olefin)⫺1.

Table 3 Initial catalyst screening for epoxidation of cyclohexene in

2,2,2-trifluoroethanol a

Catalyst TOF0 b Yield (%) c Selectivity (%) d

1 250 88 90
2 140 80 90
3 120 73 94
4 190 78 88
5 150 68 79
6 200 80 80
7 260 73 81
8 160 27 25
9 150 73 95
10 130 57 70
11 4 2 7
12 320 8 8.4
a
Conditions: 1 mol% catalyst (based on active ArSe(O)O2H), 2 mmol
cyclohexene, 4 mmol 60% H2O2, 2 ml CF3CH2OH, T = 20 ⬚C, t = 1 h.
b
TOF0 = initial rate in mmol product (mmol catalyst)⫺1 h⫺1. c GC-yield
on epoxide. d Selectivity = mmol epoxide (mmol converted olefin)⫺1.

reaction, but significant cyclohexane-1,2-diol formation was

observed when pyrazole was used as a base, which probably
explains why the reaction slowed down. The low pKa of
pyrazole may not be sufficient to scavenge all acids present,
Fig. 2 Selenium compounds tested for catalytic activity. preventing diol formation and addition of larger amounts of
base would inhibit the reaction too drastically. On the other
the product.22 Since 2,2,2-trifluoroethanol was by far superior hand, addition of Na2HPO4 gives good reactivity but induces
to other solvents further reactions were carried out in this formation of a large number of side-products, which leaves
medium. NaOAc as the optimum base for cyclohexene epoxidation in
2,2,2-trifluoroethanol. Table 2 also shows that probably only
Base effects Brønsted basicity is involved since the bases are not expected to
coordinate to the metal centre as in epoxidation reactions with
Generally speaking, epoxidation reactions that remain selective
e.g. MTO.27
in the course of time also maintain a high reaction rate because
it is often the side-products (vic-diols) that inhibit catalytic
Substituent effects
activity.23 Therefore, sensitive epoxides (e.g. 1,2-epoxycyclo-
hexane) are best prepared in the presence of mild bases which Earlier reports show that the presence of nitro-groups in
neutralise the acidic H2O2 solution from pH ~ 2.5 to 4.5–5.24 areneseleninic acids—preferably at the ortho-position—
Tertiary amines, for example, are known to accelerate epoxid- improves catalysis.17 A second nitro-group—placed at the para-
ation with MTO 6 and other systems.25 For epoxidations with position—did not improve results further, which might imply
hydrogen peroxide it is important to add a weakly nucleophilic an optimum in electronegativity of the aryl ring. Therefore, we
base with a pKa ~ 2–7.5 (in water), which is stable towards tested a fairly extensive range of selenium compounds (Fig. 2,
hydrogen peroxide 26 (Table 2). Tables 3 and 4).
As shown in Table 2 the addition of bases with pKa ranging Tables 3 and 4 show a general trend that both reactivity and
from 2.5 to 7.2 resulted in a substantial improvement in rate selectivity of the selenium catalysts increase through the
and selectivity of cyclohexene epoxidation. With 0.5% of 1 (1 addition of acetate. Under optimised conditions, most diaryl
mol% active ArSe(O)O2H) and 0.2% of base the conversion of diselenides show selectivities of (95 ± 4)% with bis[2,4-bis(tri-
cyclohexene was already ca. 90% after 15 minutes. This necessi- fluoromethyl)phenyl] diselenide (2) and bis(4-nitrophenyl)
tated a reduction of the amount of catalyst to 0.25 mol% (0.5 diselenide (8) being negative exceptions. For most diaryl
mol% active ArSe(O)O2H) to follow the reaction more accur- diselenides the initial turnover rate is roughly (400 ± 20) h⫺1,
ately. The optimum amount of base was found to be 0.1 to 0.3 while the bis(2-nitrophenyl) diselenide (6) and 8 react more
mol%. Below these values the selectivity decreased and above slowly (300 h⫺1) and show a larger tendency to destroy the more
these values the reactivity decreased significantly in all three sensitive epoxides, such as 1,2-epoxycyclohexane.17 The bis-
cases. At the optimum concentration all three bases improve the (nitrophenyl) diselenides 6 and 8 both give rise to cyclohexane-

J. Chem. Soc., Perkin Trans. 1, 2001, 224–228 225

Table 4 Catalyst screening for epoxidation of cyclohexene under sion can be reached in ca. 4 hours. Allylic alcohols such as
optimised conditions a 3-methylpent-2-en-1-ol are selectively oxidised, albeit at a
relatively low rate, again due to the decreased electron density
Catalyst TOF0 b Yield (%) c Selectivity (%) d at the double bond. Furthermore, the alcohol functionality
can be protected with methyl, acetyl or trimethylsilyl groups
1 420 98 99 (cf. citronellol † in Table 5) which are not affected during
2 390 85 86 epoxidation.
3 390 73 93
4 470 81 95
5 420 82 98 Conclusions
6 300 83 95
7 360 80 98 3,5-Bis(trifluoromethyl)benzeneseleninic acid is an effective
8 300 75 80 catalyst for epoxidation of olefins. Electron withdrawing sub-
9 230 64 91 stituents on the benzene ring, preferably with inductive proper-
10 220 70 88
11 150 2 7
ties only, give the best results in epoxidations. The best solvent
12 450 21 27 for epoxidations is 2,2,2-trifluoroethanol. Addition of sodium
blank — 1e — acetate improves results allowing effective formation of more
a
Conditions: 0.5 mol% catalyst (based on active ArSe(O)O2H), 2 mmol
delicate epoxides with organoselenium catalysts for the first
cyclohexene, 0.2 mol% NaOAc, 4 mmol 60% H2O2, 2 ml CF3CH2OH, time.
T = 20 ⬚C, t = 1 h. b TOF0 = initial rate in mmol product (mmol
catalyst)⫺1 h⫺1. c GC-yield on epoxide. d Selectivity = mmol epoxide
(mmol converted olefin)⫺1. e After 16 h.
Experimental
Catalytic reactions
1,2-diol formation after ca. 45 and 15 minutes, respectively, Hydrogen peroxide (60%, 4 mmol, 200 µl) was added to a
which is only partly solved through the addition of NaOAc. It stirred solution (1000 rpm) of the appropriate amount of
indeed seems that the strong electron withdrawing properties catalyst (0.5–1 mol% on active ‘Se’) in 2 ml of solvent in a
combined with the resonance effect of the nitro substituent closed flask. After the solution had become colourless, dibutyl
make the seleninic acid too acidic and thus promote hydrolysis ether (0.4 mmol, 67 µl) as internal standard and olefin (2 mmol)
of the epoxides, yielding vic-diols that in turn react with the were added. The reaction temperature was kept at (20 ± 1) ⬚C
catalyst and slow the reaction down. A less likely possibility is with a water bath. Samples (~50 µl) were first treated with
that mainly in the cases of 6 and 8 the aryl–selenium bond is MnO2 (10 mg) ⫹ MgSO4 in Et2O (2 ml) and subsequently fil-
cleaved—as was observed by Sharpless and others.17 The likely tered and analysed with GC. Identities of the epoxides were
product resulting from decomposition—SeO2—would have had confirmed by GC–MS and by comparing retention times with
a deleterious effect on the selectivity of the reaction, since in those of commercially available epoxides.
our case SeO2 is highly reactive, but unselective. However,
Sharpless observed similar poor reactivity of 8, where in that Synthesis
case SeO2 was not reactive. Also, reaction of cyclohexene with a Catalysts 1 to 5, 8 and 10 were synthesised from the correspond-
solution of 1 or 8 in 2,2,2-trifluoroethanol activated 16 hours ing arylmagnesium bromides and metallic selenium according
earlier with H2O2 did not give different results to a freshly pre- to the method of Reich et al.29 Catalyst 7 was prepared via
pared catalyst solution. Both observations indicate that SeO2 nitration of diphenyl diselenide 30 to the 3-nitrophenylseleninic
plays no part in the reaction. acid 31 and subsequent reduction with hydrazine dihydrogen
Substitution of the aromatic ring with two trifluoromethyl sulfate.31 Catalyst 8 was synthesised from p-nitroaniline via
groups at the meta-positions gives by far the best catalyst 1, diazotation to the p-nitrophenyl selenocyanate and treatment
which is significantly better than catalysts with only one tri- with sodium methanolate.32 The methyl,33 trimethylsilyl 34 and
fluoromethyl substituent (3–5), or with two trifluoromethyl acetate 35 derivatives of citronellol were synthesised according
substituents placed at ortho- and para-positions (2). In the case to known literature procedures.
of trifluoromethyl substituents there is only an inductive (elec-
tron withdrawing) effect, which seems to give the optimum Bis[3,5-bis(trifluoromethyl)phenyl] diselenide 1. Diselenide 1
results. Similarly, the m-nitro substituent of diselenide 7 can was crystallised from n-pentane to give dark yellow transparent
also just show an inductive effect and gives slightly better plates (2.3 g, 3.9 mmol, 79%), purity = 99.9% (GC).36 Mp =
results than 6 or 8. Catalysts 9 and 10 are influenced through 65 ⬚C (n-pentane); δH(400 MHz; CDCl3; Me4Si) 8.03 (4 H, s,
the electron withdrawing effect of the p-fluoro and p-chloro H2 ⫹ H2⬘ ⫹ H6 ⫹ H6⬘), 7.79 (2 H, s, H4 ⫹ H4⬘); δC(100 MHz;
substituents, but in these cases the resonance effect is reversed CDCl3; Me4Si) 132.7 (4 C, q, JCF 33.6, C3 ⫹ C3⬘ ⫹ C5 ⫹ C5⬘),
and the catalysts are selective, but considerably less reactive. 132.3 (C1 ⫹ C1⬘), 131.6 (C2 ⫹ C2⬘ ⫹ C6 ⫹ C6⬘), 122.7 (4 C,
With the bis(pentafluorophenyl) diselenide 11 poor results JCF 273.1, 4 × CF3), 122.3 (C4 ⫹ C4⬘); m/z (EI) 586.861 (M⫹
were obtained, possibly because the pentafluorophenyl ring is with Se2 pattern, 80%), 567 (22, M ⫺ F), 293 (100, M ⫺ 3,5-
involved in side-reactions. (CF3)2C6H3Se), 291 (66), 273 (40), 213 (41), 163 (25).

Epoxidation under optimised conditions Bis[2,4-bis(trifluoromethyl)phenyl] diselenide 2. Diselenide 2

The results of epoxidation of a variety of olefins with the was purified over silica, Rf = 0.57 (petroleum ether–EtOAc
optimised catalyst system are shown in Table 5. 95 : 5) to give light yellow plates (1.6 g, 2.8 mmol, 81%),
A representative selection of mono-, di- and tri-substituted purity = 99.9% (GC). Mp = 74–76 ⬚C (n-pentane); δH(400 MHz;
olefins was studied and the order of reactivity roughly followed CDCl3; Me4Si) 8.02 (2 H, d, J 8.4, H6 ⫹ H6⬘), 7.87 (2 H, s,
that observed with peracids (relative rates in parentheses): CH2᎐ H3 ⫹ H3⬘), 7.68 (2 H, d, J 8.4, H5 ⫹ H5⬘); δC(100 MHz;
CH2 (1) < RCH᎐᎐CH2 (25) < ArCH᎐᎐CH2 (60) < RCH᎐᎐CHR and CDCl3; Me4Si) 133.7 (C6 ⫹ C6⬘), 133.0 (C1 ⫹ C1⬘), 130.5 ⫹
R2C᎐᎐CH2 (500–600) < R2C᎐᎐CHR (6000–6500).3,28 This is con- 130.4 (4 C, 2q, JCF 34.0 and 32.2, C2 ⫹ C2⬘ ⫹ C4 ⫹ C4⬘), 129.4
sistent with the active oxidant (ArSe(O)OOH) being electro- (C5 ⫹ C5⬘), 123.9 (C3 ⫹ C3⬘), 123.2 (4 C, q, JCF 274.1,
philic in nature and the oxygen transfer to the olefin being the o-CF3 ⫹ o-CF3⬘ ⫹ p-CF3 ⫹ p-CF3⬘); m/z 586.861 (M⫹ with Se2
rate-limiting step. The α-olefins react slowly as expected, but
with increased amounts of catalyst (~5 mol%) complete conver- † The IUPAC name for citronellol is 3,7-dimethyloct-6-enol.

226 J. Chem. Soc., Perkin Trans. 1, 2001, 224–228

Table 5 Olefin epoxidation in 2,2,2-trifluoroethanol with 1 under optimised conditions a

Alkene TOF0 b Time/h Yield (%) c Selectivity (%) d

e
12 4 25 99

190 1 74 95

860 0.5 ≥99 ≥99

80 4 12 23

e
600 1 99 ≥99

420 1 98 99

620 0.5 ≥99 ≥99

380 2 74 84

400 1 99 ≥99

>750 0.5 95 95

>750 0.5 95 95

>750 0.5 95 95

a
Conditions: 0.25 mol% 1, 2 mmol olefin, 0.2 mol% NaOAc, 4 mmol 60% H2O2, 2 ml 2,2,2-trifluoroethanol, T = 20 ⬚C. b TOF0 = initial rate in mmol
product (mmol catalyst)⫺1 h⫺1. c Yield on epoxide. d Selectivity = mmol epoxide (mmol converted olefin)⫺1. e No NaOAc added, since epoxides are
stable.

pattern, 79%), 567 (10, M ⫺ F), 332 (10), 293 (100, M ⫺ 2,4- Solvents: 2,2,2-trifluoroethanol (99⫹%), α,α,α-trifluoro-
(CF3)2C6H3Se), 274 (32) 213 (32). toluene (99⫹%), nitromethane (98%), anhydrous THF
(99.5⫹%) and anhydrous Et2O (99.5⫹%) were purchased
Bis(3-nitrophenyl) diselenide 7. Diselenide 7 was crystallised from Fluka. Dichloromethane (99.5⫹%), 1,2-dichloroethane
from methanol to give fine dark-yellow needles (2.5 g, 6.2 (99⫹%) sulfuric acid (96%) and concentrated nitric acid (65%)
mmol, 70% overall), purity = 99.9% (GC). Mp = 82–83 ⬚C were purchased from Baker. Fuming nitric acid (100%) was
(lit.:31 81–83 ⬚C); δH(400 MHz; CDCl3; Me4Si) 8.47 (2 H, t, purchased from Merck. Sulfolane (99⫹%) was purchased from
J 1.8, H2 ⫹ H2⬘), 8.12 (2 H, ddd, J 8.2, 2.2 and 1.0, H4 ⫹ H4⬘), Acros.
7.92 (2 H, ddd, J 7.9, 1.7 and 1.0, H6 ⫹ H6⬘), 7.48 (2 H, t, All solvents and reagents were used without further puri-
J 8.0, H5 ⫹ H5⬘); δC(100 MHz; CDCl3; Me4Si) 148.3 fication.
(C3 ⫹ C3⬘), 136.8 (C6 ⫹ C6⬘), 131.8 (C1 ⫹ C1⬘), 130.2
(C5 ⫹ C5⬘), 126.0 (C2 ⫹ C2⬘), 123.0 (C4 ⫹ C4⬘). Analysis
Column chromatography was performed with silica gel (particle
Materials size 0.063–0.200 mm) from Merck. Melting points were deter-
Reagents: 3,5-bis(trifluoromethyl)bromobenzene (99%), 2,4- mined with a Buchi 510 Melting Point Apparatus with open
bis(trifluoromethyl)bromobenzene (98%), o-trifluoromethyl- capillary. GC measurements were carried out with a Varian Star
bromobenzene (99%), m-trifluoromethylbromobenzene (99%), 3400 equipped with a CP Sil 5-CB column (50 m × 0.53 mm).
1
p-trifluoromethylbromobenzene (99%), bromopentafluoro- H-NMR and 13C-NMR spectra were carried out on a Varian
benzene (99%), KSeCN (99%), bis(2-nitrophenyl) diselenide VXR 400S spectrometer at 400 MHz and 100 MHz, respect-
(97%), bis(4-chlorophenyl) diselenide (98%), 4-bromofluoro- ively. Chemical shifts (δ) relative to tetramethylsilane (TMS).
benzene (99%), bromobenzene (99%) and hydrazine dihydrogen Gas chromatography/mass spectrometry (GC/MS) analyses
sulfate (99⫹%) were purchased from Acros. Cyclohexene were performed on a VG 70-SE mass spectrometer equipped
(99.5%), cyclooctene (95%), oct-1-ene (97⫹%), 2-methylhept-2- with a CP Sil 5-CB column.
ene (98%) and pyrazole (98%) were purchased from Fluka.
Styrene (99⫹%), 2-methylhept-1-ene (99%), 1-methylcyclo- References
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Interox. of Organic Chemicals, Wiley-VCH, Weinheim, 1999, vol. 4, p. 1987.

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