A catalytic, environmentally benign method for the epoxidation of unsaturated terpenes with hydrogen peroxide

Article abstract of DOI:10.1016/j.tetlet.2006.04.047

Various unsaturated terpenes were selectively oxidised to the corresponding epoxides in good yields using phosphate buffered hydrogen peroxide and catalytic amounts of tungstate under halide free conditions. The selectivity of the reaction to epoxides was significantly increased with respect to the ionic strength of the aqueous phase of the system.

Full text of DOI:10.1016/j.tetlet.2006.04.047

Tetrahedron Letters 47 (2006) 4461–4463
A catalytic, environmentally benign method for the epoxidation
of unsaturated terpenes with hydrogen peroxide
Georgia Grigoropoulou and James H. Clark*
Centre for Clean Technology, Chemistry Department, University of York, York YO10 5DD, UK
Received 10 February 2006; revised 5 April 2006; accepted 10 April 2006
Available online 11 May 2006
Abstract—Various unsaturated terpenes were selectively oxidised to the corresponding epoxides in good yields using phosphate buf-
fered hydrogen peroxide and catalytic amounts of tungstate under halide free conditions. The selectivity of the reaction to epoxides
was significantly increased with respect to the ionic strength of the aqueous phase of the system.
Ó 2006 Elsevier Ltd. All rights reserved.
The oxidation of terpenes is an important industrial
application as their epoxides are used as starting materi-
als in the synthesis of commercially important fragrance
and flavour materials.1 One of the most used epoxida-
tion methods in the fine chemicals industry is the stoichio-
metric peracid route using acids such as peracetic acid
and m-chloroperbenzoic acid.2 The employment of per-
acids is not a clean method as equivalent amounts of
acid waste are produced. The safety issues associated
with handling peracids are also a matter for concern.
Therefore, there is a strong need for catalytic epoxida-
tion methods which employ safer oxidants and produce
little waste. The employment of hydrogen peroxide is an
attractive option both on environmental and economic
grounds.3 It is cheap, readily available and gives water
as the only by-product.
Noyori conditions without expensive phosphonic acids
and halo auxiliaries but optimised with respect to pH
and ionic strength.
Limonene (1) was chosen as a model substrate. It
has been oxidised to limonene oxide (1a) with hydro-
gen peroxide in the presence of catalytic amounts of
sodium tungstate under various reaction conditions
(Table 1).
The oxidation of 1 in the presence of a catalytic system
which consists of sodium tungstate dihydrate, (amino-
methyl)phosphonic acid and methyltri-n-octylammo-
nium hydrogen sulfate6 in a 2:1:1 ratio, resulted in
high conversion but low selectivity to limonene oxide
(45%), entry 1.
Tungsten-based catalysts have been shown to be very
effective in some epoxidations using hydrogen peroxide.
Reactions are carried out under biphasic phase transfer
catalysed conditions and require the employment of halo-
genated solvents4 and the use of a preformed catalyst.
An improved catalytic system under halide free condi-
tions was developed by Noyori5 but requires the use of
aminomethyl phosphonic acid additive and fails to pro-
duce acid sensitive epoxides due to their hydrolytic
decomposition under the acidic conditions.
The use of a phosphate buffer solution of H3PO4/NaH2-
PO4 (0.1 M made in H2O2 solution) as a phosphate
source increases significantly the selectivity of the reac-
tion to epoxide. Addition of a 7:3 molar ratio of
H3PO4/NaH2PO4 solution to the reaction mixture
(initial pH of aqueous phase 2.5) results in high conver-
sion and an increased selectivity to limonene oxide
(66%), entry 2. The use of a 5:5 molar ratio of H3PO4/
NaH2PO4 solution to the reaction mixture (initial pH
of aqueous phase 3.0) is not beneficial to the selectivity
of the reaction and it also results in a decrease of the
reaction rate, entry 3.
We report here the synthesis of several acid labile epox-
ides from a range of terpenes (Scheme 1) under pseudo-
The effect of the counter anion of the methyltri-n-octyl-
ammonium salt was investigated and it was found that
dihydrogen phosphate7 compared to hydrogen sulfate
*
Corresponding author. E-mail: jhc1@york.ac.uk
0040-4039/$ - see front matter Ó 2006 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2006.04.047

4462
G. Grigoropoulou, J. H. Clark / Tetrahedron Letters 47 (2006) 4461–4463
O
1
1a
O
O
OH
OH
OH
OH
2
2a
3
3a
O
O
O
O
O
O
O
O
O
O
4
4a
5
5a
OH
O
O
O
OH
OH
7b
6
6a
7
7a
Scheme 1. Unsaturated terpenes and the corresponding reaction products.
a
Table 1. Epoxidation of limonene with 30% H2O2
large amounts of sodium sulfate are added to the
system.
Entry
Time (min)
Conversion (%)
Selectivity to 1a (%)
1b
2
60
30
120
120
60
95
98
98
39
92
94
45
66
64
69
79
81
Furthermore, the increase of the volume of the solvent
added to the reaction mixture is beneficial for both the
conversion and selectivity of the reaction, entry 6.
3
4c
5d
6d,e
Our optimised method was successfully expanded to
other terpene substrates (Table 2).
120
a Reaction conditions: limonene (20 mmol), H2O2 (30 mmol),
Na2WO4Æ2H2O (0.4 mmol), [(n-C8H17)3NCH3]HSO4 (0.2 mmol),
H3PO4/NaH2PO4 (0.2 mmol) in toluene (4 mL) at 70 °C.
b NH2CH2PO3H2 was used instead of H3PO4/NaH2PO4.
c [(n-C8H17)3NCH3]H2PO4 was used instead of [(n-C8H17)3NCH3]-
HSO4.
It was found that both geraniol (2) and nerol (3) affor-
ded the 2,3-epoxides (2a, 3a) with high to moderate
selectivities (81% and 47%, respectively). The observed
regioselectivity in the oxidation of geraniol and nerol
is not unexpected, as it has been demonstrated before10
that in the presence of tungsten metal catalysts a com-
plex is possibly formed involving the metal centre, the
d Addition of Na2SO4(1 mmol).
e 15 mL of toluene.
results in a significant decrease in the conversion of
limonene but does not alter the selectivity of the reac-
tion, entry 4. The low efficiency with dihydrogen phos-
phate is probably due to a higher initial pH value of
the aqueous phase (pH 3.3).
Table 2. Epoxidation of a range of different terpenes under the
optimum reaction conditions9
Substrate
Time Conversion Yield Selectivity to
(min) (%)
(%)
epoxide (%)
Geraniol 2
Nerol 3
Geranyl acetate 4 120
Neryl acetate 5
3-Carene 6
30
30
98
99
90
95
93
80
47
71
59
88
81
47
80
62
95
The addition of sodium sulfate to increase the ionic
strength of the aqueous phase results in a significant in-
crease of the selectivity to epoxide, entry 5. The hydro-
lytic decomposition of epoxide slows down as the
water content of the organic phase decreases8 when
120
240

G. Grigoropoulou, J. H. Clark / Tetrahedron Letters 47 (2006) 4461–4463
4463
5. (a) Sato, K.; Aoki, M.; Ogawa, M.; Hashimoto, T.;
Noyori, R. J. Org. Chem. 1996, 61, 8310–8311; (b) Sato,
K.; Aoki, M.; Ogawa, M.; Hashimoto, T.; Panyella, D.;
Noyori, R. Bull. Chem. Soc. Jpn. 1997, 70, 905–915.
6. Sato, K.; Hyodo, M.; Aoki, M.; Zheng, X. Q.; Noyori, R.
Tetrahedron 2001, 57, 2469–2476.
oxidant and the substrate through OH coordination.
The oxidation of geranyl acetate (4) and neryl acetate
(5) gave the 6,7-epoxides 4a and 5a in good selectivities
(80% and 62%, respectively). The epoxidation takes
place preferably, as expected, at the C6–C7 double
bond, which has higher electron density compared to
the C2–C3 double bond.
7. Procedure for the preparation of trioctylmethylammo-
nium dihydrogen phosphate: a round-bottomed flask
(500 mL) equipped with a magnetic stirring bar was
charged with [(n-C8H17)3NCH3]Cl (4.042 g, 10 mmol),
34% H3PO4 (168 mL, 1 mol) and toluene (150 mL). The
biphasic mixture was vigorously stirred at room temper-
ature for 12 h. The aqueous phase was removed and 34%
H3PO4 (168 mL, 1 mol) was added to the organic phase
and the mixture vigorously stirred at room temperature
for 12 h. The organic phase was separated, dried over
Na2SO4, filtered and toluene was removed under vacuum.
8. Starks, C. M.; Liotta, C. L.; Halpern, M. Phase-transfer
Catalysis: Fundamentals, Applications, and Industrial Per-
spectives; Chapman & Hall: New York, 1994; p 41.
9. Procedure for the epoxidation of terpenes under optimised
conditions: a round-bottomed flask (50 mL) was charged
with Na2WO4Æ2H2O (0.132 g, 0.4 mmol), [(n-C8H17)3-
NCH3]HSO4 (0.093 g, 0.2 mmol), a 30% H2O2/phosphate
solution (3.49 mL) (the solution was prepared by mixing
0.1 M H3PO4 solution made in H2O2 and 0.1 M NaH2PO4
solution made in H2O2, in a 7:3 molar ratio) and Na2SO4
(0.142 g, 1 mmol). The mixture was vigorously stirred at
room temperature for 10 min and then was heated at
70 °C. To this, the substrate (20 mmol) and tetradecane
(1.04 mL, 4 mmol) as internal standard dissolved in
toluene (15 mL) were added. The reaction mixture was
vigorously stirred for 2 h at 70 °C and aliquots were taken
during the reaction and analysed by GC. The yields of
products were estimated from the peak areas based on the
internal standard technique. Products were identified by
1H and 13C NMR. Spectra were compared with those of
authentic compounds for 1a and with listed data for 2a,
3a, 4a, 5a, 6a, 7a and b.11
Furthermore, the main product of the oxidation of 3-
carene (6) was 3,4-epoxycarene (6a) with high selectivity
(95%). Finally, linalool (7) was transformed with 91%
conversion but no epoxide product was detected. Some
of the identified reaction products were the tetrahydro-
furan derivative 7a with low selectivity (26%) and the
tetrahydropyran derivative 7b (14% selectivity).
In summary, a variety of terpenes were selectively oxi-
dised with 30% H2O2 and a phosphotungstate catalytic
system, to the corresponding epoxides in good yields
under halide free conditions.
Acknowledgements
We thank Quest International for supporting this work
and Dr. Jacob Elings for helpful discussions.
References and notes
1. Bauer, K.; Garbe, D.; Surburg, H. Common Fragrance and
Flavor Materials; Wiley-VCH: New York/Weinheim,
1997.
2. Swern, D. In Organic Peroxides; Swern, D., Ed.; Wiley
Interscience: New York, 1971; Vol. 2.
3. (a) Jones, C. W. Applications of Hydrogen Peroxides and
Derivatives; Royal Society of Chemistry: Cambridge,
1999; (b) Noyori, R.; Aoki, M.; Sato, K. Chem. Commun.
2003, 1977–1986; (c) Lane, B. S.; Burgess, K. Chem. Rev.
2003, 103, 2457–2473; (d) Grigoropoulou, G.; Clark, J. H.;
Elings, J. A. Green Chem. 2003, 5, 1–7; (e) Arends, I. W. C.
E.; Sheldon, R. A. Top. Catal. 2002, 19, 133–141.
4. (a) Venturello, C.; Alneri, E.; Ricci, M. J. Org. Chem.
1983, 48, 3831–3833; (b) Venturello, C.; D’Aloisio, R.
J. Org. Chem. 1988, 53, 1553–1557; (c) Ishii, Y.; Yama-
waki, K.; Ura, T.; Yamada, H.; Yoshida, T.; Ogawa, M. J.
Org. Chem. 1988, 53, 3587–3593.
10. Sakagushi, S.; Nishiyama, Y.; Ishii, Y. J. Org. Chem.
1996, 61, 5307–5311.
11. (a) See Ref. 10; (b) Martins, R. R. L.; Neves, M. G. P. M.
S.; Silvestre, A. J. D.; Simoes, M. M. Q.; Silva, A. M. S.;
Tome, A. C.; Cavaleiro, J. A. S.; Tagliatesta, P.; Crestini,
C. J. Mol. Catal. 2001, 172, 33–42; (c) Fdil, N.; Romane,
A.; Allaoud, S.; Karim, A.; Castanet, Y.; Mortreux, A.
J. Mol. Catal. 1996, 108, 15–21; (d) Villa de, P. A. L.; Sels,
B. F.; De Vos, D. E.; Jacobs, P. E. J. Org. Chem. 1999, 64,
7267–7270; (e) Saladino, R.; Neri, V.; Pellicia, A. R.;
Mincione, E. Tetrahedron 2003, 59, 7403–7408.