Oxidation of alkenes with hydrogen peroxide, catalyzed by boron trifluoride. Synthesis of vicinal methoxyalkanols

Article abstract of DOI:10.1134/S1070363208040130

In oxidation of alkenes with the BF₃-H₂O₂ system, boron trifluoride induces transfer of available oxygen from hydrogen peroxide, accompanied by the formation of epoxides. The oxidation in methanol occurs as a one-pot two-step process involving epoxidation of the C=C bond followed by opening of the oxirane ring, with the formation of methoxyalkanols.

Full text of DOI:10.1134/S1070363208040130

ISSN 1070-3632, Russian Journal of General Chemistry, 2008, Vol. 78, No. 4, pp. 592–596. © Pleiades Publishing, Ltd., 2008.
Original Russian Text © A.O. Terent’ev, K.A. Boyarinova, G.I. Nikishin, 2008, published in Zhurnal Obshchei Khimii, 2008, Vol. 78, No. 4, pp. 611–615.
Oxidation of Alkenes with Hydrogen Peroxide,
Catalyzed by Boron Trifluoride.
Synthesis of Vicinal Methoxyalkanols
A. O. Terent’ev, K. A. Boyarinova, and G. I. Nikishin
Zelinskii Institute of Organic Chemistry, Russian Academy of Sciences,
Leninskii pr. 47, Moscow, 119991 Russia
e-mail: terentev@ioc.ac.ru
Received August 30, 2007
Abstract—In oxidation of alkenes with the BF3–H2O2 system, boron trifluoride induces transfer of available
oxygen from hydrogen peroxide, accompanied by the formation of epoxides. The oxidation in methanol occurs
as a one-pot two-step process involving epoxidation of the C=C bond followed by opening of the oxirane ring,
with the formation of methoxyalkanols.
DOI: 10.1134/S1070363208040130
The development of new methods for oxidation of
unsaturated componds attracts enduring interest of or-
ganic chemists. An appreciable share of studies in this
field concern the search for catalysts that transfer
available oxygen from hydrogen peroxide. These
studies are performed within the framework of the
development of methods of fine organic synthesis. At
the same time, they also serve as a basis for the
development of commercial-scale oxidation processes,
because hydrogen peroxide is cheap and environmen-
tally friendly. Compounds of many metals (W, V, Mo,
Rh, Re, Ir, Ru, Pd, Ti, Co, Mg, Cu, Mn, Fe, Zr, Ag, Cr,
Au are used as catalysts of oxidative transformations
involving H2O2 [1–7].
oxidizing species is per acid generated in situ from
hydrogen peroxide and carboxylic acid, have been
reported [8].
We used previously the BF3–H2O2 system for
preparing geminal bishydroperoxides from enol ethers
[9]. In this study, when attempting to perform hydro-
peroxidation of related unsaturated compounds, al-
kenes, we discovered that in this system boron trifluo-
ride, commonly known as a Lewis acid, shows a
different behavior, inducing oxygen transfer from
hydrogen peroxide to alkene. In oxidation of alkenes
Ia–If in methanol, the major products are epoxides
IIa–IIf and methoxyalkanols IIIa–IIIf (Scheme 1).
Alkyl hydroperoxides were not detected, although it
was reported that they are formed in oxidation of
alkenes with H2O2, catalyzed by acids (e.g., H2SO4)
[10, 11].
Boron-containing catalysts in combination with
hydrogen peroxide were not used for oxidation of
alkenes. Only oxidation reactions with perborates,
performed in carboxylic acids, in which the actual
Scheme 1. Oxidation of alkenes Ia–If with the BF3–H2O2 system in MeOH
OMe
BF3, H2O2
MeOH
BF3, MeOH
O
OH
IIIа_IIIf
Ia_If
IIа_IIf
592

OXIDATION OF ALKENES WITH HYDROGEN PEROXIDE
593
The capability of H2O2 in combination with BF3 to
induce Baeyer–Villiger oxidative rearrangement of
ketones is well known [12, 13]. It is assumed in these
papers that initially H2O2 and then the product of
addition of H2O2 to the ketone form with BF3 a com-
plex in which the O–O bond is polarized, which is the
necessary condition for the rearrangement to occur.
Apparently, polarization of the O–O bond in the BF3–
H2O2 system imparts to the peroxy fragment the prop-
erties of a per acid which is the active species oxidiz-
ing the alkenes. Boron trifluoride is coordinated with
the forming epoxide II and in the absence of an ex-
ternal nucleophile induces its polymerization and iso-
merization into a ketone. To make the synthesis of
methoxyalkanols III more selective and prevent side
reactions, the oxidation was performed in excess
methanol. Previously BF3 was already used as acid
catalyst for opening of the oxirane ring with alcohols
[14–18]. The interest in this reaction is due to the fact
that opening of epoxides (e.g., styrene or indene epox-
ide [15], or glycidyl ethers [16–18]) with an alcohol
yields, as a rule, a single regioisomer.
from 20 to 22, and from 35 to 38°C. As follows from
Table 1, the temperature strongly affects the conver-
sion of cyclooctene and the composition and yield of
the products.
In the temperature range from –16 to 22°C, oxida-
tion of cyclooctene Ic is slow. For example, at 20–22°C
70% conversion of cyclooctene was attained only in 80 h.
At 35–38°C, the oxidation rate noticeably increases,
and 41% conversion is attained in 4 h. An increase in
the amount of BF3·Et2O from 0.5 to 1 equiv also
accelerates the reaction: The conversion of Ic in 4 and
5 h becomes 75 and 91%, respectively.
Oxidation of Ia–If (Table 2) was performed under
the conditions optimal for selective formation of
methoxyalkanols. Namely, the majority of experiments
were performed at 40–42 and 50–55°C in excess
MeOH.
Thus, alkenes Ia–If in the temperature ranges 40–
42 and 50–55°C in 10–22 h under the action of a
threefold molar excess of H2O2 and one- or twofold
molar excess of BF3·Et2O undergo oxidation with a
high degree of conversion (80–100%). The oxidation
results only slightly depend on the structure of the
starting cycloalkene Ia–If. Methoxyalkanols IIIa–IIIf
were prepared under optimized conditions in 61–72%
yields, which is a good result taking into account the
two-step reaction course (epoxidation followed by ring
opening).
The objects of our study were cycloalkanes (cyclo-
pentene Ia, cyclohexene Ib, cyclooctene Ic, cyclo-
odecene Id; Id, as a mixture of cis and trans isomers)
and alkenes with the double bond conjugated with an
aromatic ring (styrene Ie, indene If).
The influence of the experimental conditions on the
reaction of olefins with the BF3–H2O2 system was
studied with oxidation of cyclooctene Ic as example.
The reaction yielded two major products: epoxycyclo-
octane IIc and 1-hydroxy-2-methoxycyclooctane IIIc
(Scheme 2).
Table 1. Influence of reaction temperature and time on the
conversion of cyclooctene Ic and yields of oxidation
products IIc and IIIca
Mol
BF3·Et2O/
mol Ic
Yield, %b
Conversion, Time,
T, °C
%
h
Scheme 2. Oxidation of cyclooctene Ic with the BF3–H2O2
IIc
IIIc
system in MeOH
From –16
to –12c
0.5
12
120
73
10
OMe
BF3, H2O2
O
+
Ic
0–5d
0.5
0.5
0.5
1
28
70
41
75
91
120
80
4
70
57
62
45
38
12
27
28
38
42
MeOH
OH
20–22d
35–38d
35–38d
IIc
IIIc
4
35–38d
1
5
To perform the oxidation, we prepared a mixture
a
To 7% solution of H2O2 in Et2O (2.7 or 8.1 mmol of H2O2) we
added 0.3 g of cyclooctene, 0.192 or 0.384 g of BF3·Et2O, and
of methanol with a 7% solution of H2O2 in ether and
BF3·Et2O, after which compound Ic was added, and
the homogeneous mixture was kept for 4–120 h at
various temperatures: from –16 to –12, from 0 to 5,
b
2 ml of MeOH. GLC data; yields based on converted cyclo-
octene Ic. c 7% solution of H2O2 in Et2O, 2.7 mmol. d 7% solution
of H2O2 in Et2O, 8.1 mmol.
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 78 No. 4 2008

594
TERENT’EV et al.
Table 2. Results of oxidation of alkenes Ia–Ifa
Alkene
Ia
Mol Н2О2/mol I
Mol BF3·Et2O/mol I
T, °C
40–42
20–25
20–25
Time, h Conversion, %
Products, yield, %b
3
1
3
1
22
100
40
100
70
IIa, 0
IIIa, 61
IIIb, 42
IIIb, 29
0.5
1
IIb, 2
IIb, 2
Ib
41
Ib
3
3
1
3
3
3
3
1
1
2
1
2
2
1
50–55
50–55
40–42
50–55
50–55
50–55
50–55
14
12
10
15
14
16
12
100
100
80
IIb, 0
IIc, 0
IId, 2
IId, 0
IIe, 11
IIe, 0
IIf, 0
IIIb, 69
IIIc, 72
IIId, 51
IIId, 67
IIIe, 62
IIIe, 67
IIIf, 69
Ib
Ic
Idc
Idc
Ie
100
95
100
100
Ie
If
a
Reaction conditions: 2.7 mmol of alkene; 7% solution of H2O2 in Et2O (2.7 or 8.1 mmol of H2O2); 0.192, 0.384 or 0.767 g of
BF3·Et2O; 6 ml of MeOH. b Based on alkene taken into reaction. c Cyclododecene Id was used as a mixture of cis (41%) and trans (59%)
isomers.
The structure of the epoxides and methoxyalkanols
analysis was performed on Silufol UV-254 plates,
sorbent Silpearl, eluent hexane–ethyl acetate (3:1 by
volume). Column chromatography was performed with
silica gel, 63–200 mesh (Merck). Cyclopentene,
cyclohexene, cyclooctene, and indene were purchased
from Acros. Styrene (pure grade), cyclododecene (pure
grade), Et2O, hexane, MeOH, ethyl acetate,
Na2S2O3·5H2O, and 37% aqueous H2O2 (Russia) were
used without additional purification. A solution of
H2O2 in Et2O was prepared by extraction from 37%
aqueous H2O2 solution, followed by drying over
MgSO4 [23]. The concentration of peroxides was
determined by iodometric titration [24]. GC–MS
analysis was performed with a Varian 3400 chromato-
graph equipped with an HP-101 capillary column
(25 m×0.2 mm×0.2 μm). The injector temperature was
270°C. The carrier gas was helium, flow rate 1 ml min–1.
An MS Finnigan MAT ITP-700 ion trap was used.
Mass range monitored: m/z 40–300. Ionizing electron
energy 70 eV. Software: ITDS (Finnigan MAT),
version 4.10.
obtained was determined by NMR spectroscopy and
mass spectrometry. Oxidation of cyclododecene Id
taken as a mixture of isomers yielded epoxide IId as a
mixture of cis and trans isomers and 2-methoxy-1-
cyclododecanol IIId as a mixture of erythro and threo
isomers, which was confirmed by GLC–MS, doubling
of signals in the 13C NMR spectra, and comparison of
the TLC data for IId and IIId with those for the
references prepared by epoxidation of cyclododecene
and methanolysis of its epoxide [19, 20]. 1-Methoxy-
2,3-dihydro-1H-inden-1-ol IIIf was prepared as a mix-
ture of cis and trans isomers, which was found by
comparison with the known NMR spectra [21, 22]; the
isomer ratio was ~1/2 (GC–MS).
Thus, we have discovered a new property of boron
trifluoride: capability to activate hydrogen peroxide in
oxidation of alkenes in methanol. The first step
involves formation of an epoxide, and in the second
step BF3 catalyzes the epoxy ring opening with meth-
anol, yielding 2-methoxy-alkan-1-ols. Alkyl hydroper-
oxides, expected products of acid-catalyzed addition of
hydrogen peroxide, are not formed under these con-
ditions.
Oxidation of alkenes (general procedure). To a
7% solution of H2O2 in Et2O (2.7–8.1 mmol), we
added an alkene (2.7 mmol), 0.192–0.767 g of BF3·
Et2O, and 2 or 6 ml of MeOH. The homogeneous
reaction mixture was kept at a temperature from –16 to
55°C for 4–240 h. In the course of synthesis at
temperatures exceeding 35°C, the required amount of
Et2O was evaporated in the initial period of the reac-
tion to increase the boiling point of the mixture. After
the reaction completion, 40 ml of Et2O and 10 ml of a
5% solution of Na2S2O3·5H2O were added, the mixture
EXPERIMENTAL
The NMR spectra were recorded on Bruker AC-
1
13
200 (200.13 MHz for H, 50.32 MHz for C), Bruker
WM-250 (250.13 MHz for 1H, 62.9 MHz for 13C), and
1
Bruker AM-300 (300.13 MHz for H, 75.4 MHz for
13C) spectrometers in CDCl3 solutions. The TLC
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 78 No. 4 2008

OXIDATION OF ALKENES WITH HYDROGEN PEROXIDE
595
was stirred, and the ether layer was separated, washed
with 2 × 5 ml of H2O, and dried over MgSO4. The
mixtures were analyzed by GC–MS. Compounds IIb–
IIe and IIIa–IIIf were isolated pure by column
chromatography.
spectrum (250.13 MHz, CDCl3), δ, ppm: 1.18–1.70 m
(40H, CH2), 3.65–3.9 br.s (2H, OH), 3.11–3.39 m (8H,
CH3, CHOMe), 3.65–3.87 m (2H, CHOH). 13C NMR
spectrum (62.9 MHz, CDCl3), δ, ppm: 21.5–25.1 (18C,
CH2), 28.2, 29.3 (CH2), 57.1, 57.3 (CH3), 69.7, 69.9
(CHOH), 82.4, 82.7 (CHOMe). Erythro and threo
isomers. Mass spectrum, m/z (Irel, %): 214 [M]+ (3),
199 [M – CH3]+ (15), 71 (100) and 214 [M]+ (2), 199
[M – CH3]+ (14), 71 (100).
2-Methoxycyclopentanol (IIIa) [25]. Oil, Rf 0.44.
1H NMR spectrum (250.13 MHz, CDCl3), δ, ppm:
1.45–2.03 m (6H, CH2), 3.0–3.25 br.s (1H, OH), 3.31 s
(3H, CH3), 3.50–3.59 m (1H, CHCOCH3), 4.03–4.10
m (1H, CHOH). Mass spectrum, m/z (Irel, %): 116 [M]+
(9), 84 (100).
1
2-Phenyloxirane (IIe) [28]. Oil, Rf 0.81. H NMR
spectrum (300 MHz, CDCl3), δ, ppm: 2.82 d.d (1H,
CH2, J 2.6, 5.4 Hz), 3.16 d.d (1H, CH2, J 4.1, 5.4 Hz),
3.88 d.d (1H, CH, J 2.6, 4.1 Hz), 7.28–7.41 m (5H,
Ph). Mass spectrum, m/z (Irel, %): 120 [M]+ (12), 91
[PhCH2]+ (100).
7-Oxabicyclo[4.1.0]heptane (IIb) [26, 27].
1
Mobile liquid. H NMR spectrum (300 MHz, CDCl3),
δ, ppm: 1.11–1.45 m (4H, CH2), 1.69–1.94 m (4H,
CH2), 3.08 br.s (3H, OCH3).
2-Methoxy-2-phenylethanol (IIIe) [25]. Oil, Rf
0.38. H NMR spectrum (300 MHz, CDCl3), δ, ppm:
2.51–2.73 br.s (1H, OH), 3.30 s (3H, CH3), 3.58–3.71
m (2H, CH2), 4.30 d.d (1H, CH, J 3.7, 8.5 Hz), 7.27–
7.40 m (5H, Ph). Mass spectrum, m/z (Irel, %): 135 [M –
H2O]+ (2), 121 [M – MeO]+ (100).
2-Methoxycyclohexanol (IIIb) [25]. Oil. Rf 0.33.
1H NMR spectrum (250.13 MHz, CDCl3), δ, ppm:
1
0.85–2.05
m
(8H, CH2), 2.75–2.90
m
(1H,
13
CHCOCH3), 3.20–3.41 m (5H, CHOH, CH3, OH). C
NMR spectrum (62.9 MHz, CDCl3), δC, ppm: 23.7,
23.8, 28.1, 32.0, 56.0, 73.2, 84.6. Mass spectrum, m/z
(Irel, %): 130 [M]+ (45), 112 [M – H2O]+ (8), 71 (100).
1-Methoxy-2,3-dihydro-1H-inden-2-ol (IIIf) [21,
22] [mixture of cis and trans isomers, 2:1 (GLC–MS)].
Rf 0.21, 0.28. 1H NMR spectrum (300 MHz, CDCl3), δ,
ppm: 2.45–3.38 m (3H, CH2, OH), 3.54, 3.57 s (CH3),
4.46–4.68 m (2H, CH), 7.19–7.45 m (4H, CH, Ar). 13C
NMR spectrum (75 MHz, CDCl3), δ, ppm: 39.0, 39.1
(CH2), 57.1, 57.2 (CH3), 72.3, 78.0 (CHOH), 83.9,
90.3 (CHOMe), 125.1, 125.2, 125.5, 126.5, 126.8,
129.0, 139.6, 140.1, 140.13, 141.0 (C, Ar). Mass
spectrum, m/z (Irel, %): 164 [M]+ (12), 104
[PhCH=CH2]+ (100).
9-Oxabicyclo[6.1.0]nonane (IIc) [28]: mp 54–56°C
(mp 55–56°C [29]). Rf 0.81. 1H NMR spectrum
(250.13 MHz, CDCl3), δ, ppm: 1.10–1.65 m (12H,
CH2), 2.01–2.19 m (1H, CH), 2.78–2.91 m (1H, CH).
13C NMR spectrum (62.9 MHz, CDCl3), δ, ppm: 25.4,
26.1, 26.4, 55.4. Mass spectrum, m/z (Irel, %): 125 [M –
H]+ (1), 55 (100).
2-Methoxycyclooctanol (IIIc) [19]. Oil. Rf 0.49. 1H
NMR spectrum (250.13 MHz, CDCl3), δ, ppm: 1.32–
1.88 m (12H, CH2), 2.90–3.12 m (2H, CHCOCH3,
OH), 3.33 s (3H, OCH3), 3.57 m (1H, CHOH). 13C
NMR spectrum (62.9 MHz, CDCl3), δC, ppm: 23.5,
24.6, 25.7, 26.2, 26.8, 30.2, 56.3 (CH3), 74.6 (CHOH),
86.4 (CHOMe). Mass spectrum, m/z (Irel, %): 158 [M]+
(0.5), 143 [M – CH3]+ (11), 71 (100).
ACKNOWLEDGMENTS
The study was financially supported by the Pro-
gram for Support of Leading Scientific Schools of the
Russian Federation (project no. NSh 5022.2006.3),
Program of the Russian Federation President (project
no. MK-3515.2007.3), and Foundation for Support of
Domestic Science.
13-Oxabicyclo[10.1.0]tridecane (IId) [20] (mix-
1
ture of cis and trans isomers). Rf 0.82, 0.88. H NMR
spectrum (300 MHz, CDCl3), δ, ppm: 1.14–1.61 m
(36H, CH2), 1.72–2.19 m (4H, CH2CHO), 2.62–2.90 m
(4H, CHO). 13C NMR spectrum (75 MHz, CDCl3), δ,
ppm: 22.4, 23.4, 23.6, 23.8, 23.9, 24.0, 25.0, 25.5,
25.9, 26.6, 31.3 (CH2), 58.0, 58.1, 59.8, 59.9 (CHO).
Mass spectrum, m/z (Irel, %): 164 [M – H2O]+ (8), 55
(100).
REFERENCES
1. Tojo, G. and Fernandez, M., Oxidation of Alcohols to
Aldehydes and Ketones: a Guide to Current Common
Practice, New York: Springer, 2006.
2. Meyer, F. and Limberg, C., Organometallic Oxidation
Catalysis, Top. Organomet. Chem., 2007, vol. 22.
2-Methoxycyclododecanol (IIId) [19] (mixture of
erythro and threo isomers). Rf 0.52, 0.67. H NMR
1
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 78 No. 4 2008

596
TERENT’EV et al.
3. Tolstikov, G.A., Reaktsii gidroperekisnogo okisleniya
(Reactions of Hydroperoxide Oxidation), Moscow:
Nauka, 1976.
17. Guivisdalsky, P.N. and Bittman, R., J. Org. Chem.,
1989, vol. 54, no. 19, p. 4637.
18. Guivisdalsky, P.N. and Bittman, R., J. Org. Chem.,
4. Jones, C.W., Applications of Hydrogen Peroxide and
Derivatives, Royal Soc. Chem., 1999.
1989, vol. 54, no. 19, p. 4643.
19. Kas’yan, L.I., Stepanova, N.V., Belyakova, T.A.,
Kunanets, V.K., Lutsenko, A.I., and Zefirov, N.S., Zh.
Org. Khim., 1984, vol. 20, no. 11, p. 2295.
5. Strukul, G., Catalytic Oxidations with Hydrogen
Peroxide as Oxidant, Springer, 1992.
6. Lane, B.S. and Burgess, K., Chem. Rev., 2003, vol. 103,
20. Kas’yan, L.I., Stepanova, N.V., Galafeeva, M.F.,
Boldeskul, I.E., Trachevskii, V.V., and Zefirov, N.S.,
Zh. Org. Khim., 1987, vol. 23, no. 1, p. 122.
no. 7, p. 2457.
7. Butler, A., Clague, M.J., and Meister, G.E., Chem. Rev.,
21. Iranpoor, N. and Baltork, I.M., Synth. Commun., 1990,
1994, vol. 94, no. 3, p. 625.
vol. 20, no. 18, p. 2789.
8. McKillop, A. and Sanderson, W.R., J. Chem. Soc.,
Perkin Trans. 1, 2000, no. 4, p. 471.
22. Hatsui, T. and Takeshita, H., Bull. Chem. Soc. Jpn.,
1980, vol. 53, no. 9, p. 2655.
9. Terent’ev, A.O., Kutkin, A.V., Platonov, M.M.,
Vorontsov, I.I., Antipin, M.Yu., Ogibin, Yu.N., and
Nikishin, G.I., Izv. Ross. Akad. Nauk, Ser. Khim., 2004,
no. 3, p. 650.
23. Saito, I., Nagata, R., Yuba, K., and Matsuura, T.,
Tetrahedron Lett., 1983, vol. 24, no. 16, p. 1737.
24. Antonovskii, V.L. and Buzlanova, M.M.,
Analiticheskaya khimiya organicheskikh peroksidov
(Analytical Chemistry of Organic Peroxide), Moscow:
Khimiya, 1978.
10. Davies, A.G., Foster, R.V., and White, A.M., J. Chem.
Soc., 1954, p. 2200.
11. Milas, N.A. and Perry, L.H., J. Am. Chem. Soc., 1946,
25. Barluenga, J., Vazquez-Villa, H., Ballesteros, A., and
vol. 68, no. 10, p. 1938.
Gonzalez, J.M., Org. Lett., 2002, vol. 17, no. 4, p. 2817.
12. Carlqvis, P., Eclend, R., and Brinck, T., J. Org. Chem.,
26. Nicolaou, K.C., Montagnon, T., Ulven, T., Baran, P.S.,
Zhong, Y.-L., and Sarabia, F., J. Am. Chem. Soc., 2002,
vol. 124, no. 20, p. 5718.
2001, vol. 66, no. 4, p. 1193.
13. McClure, J.D. and Williams, P.H., J. Org. Chem., 1962,
vol. 27, no. 1, p. 24.
27. Lane, B.S., Vogt, M., DeRose, V.J., and Burgess, K.,
14. Petrov, A.A., Zh. Obshch. Khim., 1940, vol. 10, no. 11,
J. Am. Chem. Soc., 2002, vol. 124, no. 40, p. 11946.
p. 981.
28. Geng, X.-L., Wang, Z., Li, X.-Q., and Zhang, C., J. Org.
Chem., 2005, vol. 70, no. 23, p. 9610.
15. Liu, Y.-J., Chu, T.-Y., and Engel, R., Synth. Commun.,
1992, vol. 22, no. 16, p. 2367.
29. Betzemeier, B., Lhermitte, F., and Knochel, P., Synth.
Lett., 1999, no. 4, p. 489.
16. Guivisdalsky, P.N. and Bittman, R., J. Am. Chem. Soc.,
1989, vol. 111, no. 8, p. 3077.
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 78 No. 4 2008