Hexafluoroacetone in hexafluoro-2-propanol: A highly active medium for epoxidation with aqueous hydrogen peroxide

Article abstract of DOI:10.1055/s-2001-16037

The combination of hexafluoro-2-propanol and catalytic amounts of hexafluoroacetone gives a versatile medium for epoxidation of a wide range of alkenes with aqueous hydrogen peroxide.

Full text of DOI:10.1055/s-2001-16037

LETTER
1305
Hexafluoroacetone in Hexafluoro-2-propanol: A Highly Active Medium for
Epoxidation with Aqueous Hydrogen Peroxide
Michiel C.A. van Vliet, Isabel W.C. E. Arends, Roger A. Sheldon*
Laboratory for Organic Chemistry and Catalysis, Delft University of Technology, Julianalaan 136, 2628 BL Delft, The Netherlands
Fax +31(0)152781415; E-mail: secretariat-ock@tnw.tudelft.nl
Received 10 May 2001
was observed in halogenated solvents,1,2 but large (some-
Abstract: The combination of hexafluoro-2-propanol and catalytic
times stoichiometric) amounts of catalyst and high reac-
tion temperatures were required.
amounts of hexafluoroacetone gives a versatile medium for epoxi-
dation of a wide range of alkenes with aqueous hydrogen peroxide
In related work on catalytic epoxidation, we found that a
significant increase in reaction rate could be achieved if
the reaction was conducted in fluorinated alcohols.6 In
these alcohols even uncatalysed epoxidation occurred,
with a reasonable rate and high selectivity.7 Some alkenes
reacted somewhat sluggishly in the uncatalysed reaction.
Therefore, we investigated the combination of the fluori-
nated ketones with fluoro alcohols in the epoxidation of
alkenes with aqueous hydrogen peroxide.
Key words: epoxidation, alkenes, electrophilic addition, hydrogen
peroxide, fluoro ketone
Epoxidation of alkenes with hydrogen peroxide generally
requires a catalyst. Most efficient catalytic systems are
based on transition metals or main group elements such as
arsenic and selenium. However, a major problem with ho-
mogeneous catalysis is the contamination of the product
by traces of catalyst. The traces of metal can be highly
toxic and/or very expensive. In the former case an elabo-
rate purification of the product is required to reduce the
trace amounts of metal in the product. In the latter case an
equally difficult work-up is required to minimise losses of
the precious metal. A possible solution for the metal con-
tamination of the product is immobilisation of the cata-
lyst, but for the most efficient catalysts no adequate
immobilisation procedure is known.
Initially, we used a reactive alkene, 3-carene which forms
a single stereoisomer due to steric influences, for compar-
ison of several solvents (Table 1). The best solvent proved
to be hexafluoro-2-propanol. A much higher rate was ob-
served than in the common chlorinated solvents.
Table 1 Solvent effects in hexafluoroacetone catalysed epoxidation
of 3-carene
A totally different approach is the use of metal-free epoxi-
dation catalysts. If no metal is present no problems of re-
covery or of trace contamination by metals can occur. A
large number of metal-free epoxidations with hydrogen
peroxide is known. However, in most cases a stoichiomet-
ric amount of coreactant is present to activate the hydro-
gen peroxide. Most of the reported activation agents are
acid derivatives (forming percarboxylic acids in situ) that
generate stoichiometric amounts of a coproduct as waste.
The number of truly catalytic, metal-free epoxidation
methods using hydrogen peroxide is limited. Most notable
are those based on highly fluorinated ketones.1 These
compounds form an adduct (perhydrate) with hydrogen
peroxide which resembles percarboxylic acids in forming Conditions: 5 mol% hexafluoroacetone, 3-carene (1 M) in solvent
with 2 eq. 60% H2O2 and 0.05 eq. Na2HPO4. Stirring at room tempe-
rature. Analysis by GLC.
internal hydrogen bonds. The advantage over percarboxy-
lic acids is the uncatalysed formation of the active oxidant
with hydrogen peroxide. The formation of percarboxylic
acids from carboxylic acids and hydrogen peroxide re-
As was mentioned above, an uncatalysed epoxidation re-
quires acid catalysis which is, in most cases, incompatible
action also occurred in fluoroalcohols.7 However, the ad-
with the production of acid sensitive epoxides.
dition of a small amount of hexafluoroacetone greatly
Several reports on epoxidation with hexafluoroacetone
have appeared in the literature.1,2 Other highly halogenat-
ed ketones, e.g. hexachloroacetone,3 tetrachloroacetone4
and some mixed fluorochloroketones5 are also active in
catalytic epoxidation and have appeared in patent litera-
ture. The best catalytic performance of hexafluoroacetone
improved the epoxidation reaction. As Table 2 shows, the
initial rate did not increase very much with added catalyst,
but the reaction time required to obtain complete conver-
sion was greatly shortened. A slightly higher epoxide
yield was reached in just one tenth of the time that was re-
quired by the uncatalysed reaction.
Synlett 2001, No. 8, 1305–1307 ISSN 0936-5214 © Thieme Stuttgart · New York

1306
M. C. A. van Vliet et al.
LETTER
Table 2 Influence of added hexafluoroacetone on 3-carene epoxi-
dation in hexafluoro-2-propanol
The scope of the reaction was investigated in some more
detail with a range of functionalised cyclohexenes (Table
4). Yields of epoxides were in most cases very high, but
not quantitative. Due to the high polarity of the solvent
(per)hydrolysis and solvolysis reactions also occurred.
Most epoxides were obtained in 80-95%, with no by-
products observed with GLC. The exception was the silyl
ether, that was hydrolysed forming the epoxyalcohol in a
yield comparable to that of the hydroxyalkene substrate.
The rate of the reaction was strongly influenced by the
ability of the functional group to coordinate with hydro-
gen bond donors; functional groups able to accept hydro-
gen bonds reacted slower. However, these functionalised
alkenes bearing groups capable of forming hydrogen
bonds did not react at all in the uncatalysed reaction in
hexafluoro-2-propanol, indicating that in the uncatalysed
reaction hydrogen bonding ability has an even stronger in-
fluence.
Conditions: 2 mmol 3-carene, 0.4 mmol dibutyl ether, 0.1 mmol
Na2HPO4 and 4 mmol 60% H2O2 in 2 ml of hexafluoro-2-propanol.
The indicated amount of hexafluoroacetone was added. Stirring at
room temperature. Analysis by GLC.
The effect of the added hexafluoroacetone was even stron-
ger in the case of unreactive alkenes. In the uncatalysed
reaction, terminal alkenes were unreactive at room tem-
perature and gave only a moderate conversion at reflux
temperature.7 In the catalysed reaction even the terminal
alkenes were, although slowly, epoxidised in >90% yield
at room temperature.
Table 4 Epoxidation of funtionalised cyclohexenes catalysed by
hexafluoroacetone in hexafluoro-2-propanol
The scope of the reaction for non-functionalised alkenes
is given in Table 3, using the optimised conditions (5
mol% of catalyst and an 1 M alkene concentration in
hexafluoro-2-propanol). The reaction is quite selective. In
most catalytic experiments no by-products were observed
and the yields determined by GLC with internal standard
were nearly quantitative. Only in the case of very sensitive
epoxides (e.g. -pinene oxide) were by-products ob-
served. In some other cases the yields were lower than
quantitative, presumably by-products were formed that
could not be observed by GLC. 3-Carene epoxidation was
conducted on a somewhat larger scale and subjected to
standard work-up. A high yield (80% after distillation) of
pure epoxide was obtained on a 5 mmol scale.
Table 3 Epoxidation in a hexafluoroacetone/hexafluoro-2-propanol
mixture with aqueous hydrogen peroxide
Conditions: alkene (2 mmol), dibutyl ether (0.5 mmol), hexafluoro-
acetone (0.1 mmol), Na2HPO4 (0.1 mmol) and hydrogen peroxide (4
mmol; 60%) in hexafluoro-2-propanol (2 ml) were stirred at room
temperature. Analysis by GLC. a Epoxyalcohol.
The influence of hydrogen bonding was also noted in the
observed isomer ratio of the epoxides. This isomer ratio
cannot be easily determined with the functionalised
epoxides in which the functionality is isolated from the
cyclohexane ring with a CH2 spacer. GLC gave overlap-
ping peaks. 13C NMR did separate the two isomers, but
this is not a quantitative technique. The isomer ratio of the
epoxides with the functionality directly bonded to the
cyclohexane ring could be easily determined in a quanti-
tative manner, since GLC gave well separated peaks. The
isomer ratio was opposite to that observed for methyl-
trioxorhenium (MTO) catalysed epoxidation. MTO gives
a 1.3-1.5:1 ratio with a preference for the trans-epoxide
(epoxidation from the less hindered side of the alkene).
Conditions: 5 mol% hexafluoroacetone, Alkene (1 M) in hexafluoro-
2-propanol with 2 eq. 60% H2O2 and 0.05 eq. Na2HPO4. Stirring at
room temperature. Analysis by GLC. a Isolated yield on 5 mmol scale
81%. b Bisepoxide, 3% cymene was also formed. c Only 2,3 epoxide
was observed.
Synlett 2001, No. 8, 1305–1307 ISSN 0936-5214 © Thieme Stuttgart · New York

LETTER
Hexafluoroacetone in Hexafluoro-2-Propanol
1307
The combination of hexafluoroacetone and hexafluoro-2-
propanol showed a preference, with a slightly higher ratio,
for epoxidation from the more hindered side of the alkene,
presumably caused by hydrogen bonding of the perhy-
drate with the oxygen containing functionality.
Acknowledgement
This work was sponsered by the Dutch Innovation Oriented Rese-
arch Program on Catalysis (IOP Catalysis, IKA 96018)
References and Notes
Compared to other epoxidation methods, this method has
some advantages. The reaction is conducted under very
mild conditions. No sacrificial co-reagents or co-catalysts
are required, except for the small amount of phosphate
buffer. The catalyst and solvent are quite expensive, but
readily available on a laboratory scale for small scale re-
actions. On a larger scale advantage can be taken of the
high volatility of both catalyst and solvent for recycling.
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(5) L. Kim, Br. Pat. 1399639 (1972) to Shell Internationale
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General Procedure, epoxidation of 3-carene
3-Carene (3,3,7-trimethylbicyclo[4,1,0]hept-3-ene; 681 mg; 5
mmol), hexafluoroacetone trihydrate (55 mg; 0.25 mmol) and diso-
dium hydrogenphosphate (36 mg; 0.25 mmol) were dissolved in
hexafluoro-2-propanol (5 mL). Hydrogen peroxide (60% solution;
0.5 mL; 10 mmol) was added. The mixture was stirred at room tem-
perature for 3 hours. The solvent was removed under reduced pres-
sure. The residue was dissolved in diethyl ether (5 mL) and washed
with water (3 mL). The water was extracted with diethyl ether
(2 x 2.5 mL). The combined ether extracts were mixed with a small
amount of MnO2 to decompose traces of hydrogen peroxide and
dried on Na2SO4. The residue obtained after removal of the solvent
was distilled on a Kugelrohr apparatus. A colourless oil (612 mg;
4.03 mmol; 81%) was obtained at 75-80 C (20 mm Hg). GC:
>99.5% purity.
Article Identifier:
1437-2096,E;2001,0,08,1305,1307,ftx,en;D06901ST.pdf
1H NMR (300 MHz, CDCl3) 0.50 (ddt; 2H); 0.73 (s, 3H, Me); 1.01
(s, 3H, Me); 1.26 (s, 3H, Me); 1.49 (dd, 1H); 1.64 (dt, 1H); 2.14 (dd,
1H); 2.30 (ddd, 1H); 2.84 (br, 1H).
13C NMR (75 MHz, CDCl3) 13.8; 14.6; 16.0; 19.2; 23.1; 23.3;
27.7(d); 56.2; 58,4.
Synlett 2001, No. 8, 1305–1307 ISSN 0936-5214 © Thieme Stuttgart · New York