Dramatic enhancement of enone epoxidation rates in nonionic microemulsions

Article abstract of DOI:10.1002/chem.200600550

The ability of microemulsions to dissolve polar and non-polar components with a huge internal interface can overcome the reagent incompatibilities frequently encountered in organic reactions. We investigated model epoxidation reactions of α,β-unsaturated enones and alkaline hydrogen peroxide in different nonionic microemulsions, both in the presence and absence of a phase-transfer agent (PTA). The obtained reaction profiles were compared with those for the corresponding surfactant-free two-phase systems. In addition, we defined a time constant τ as a measure for the rate of turnover. The epoxidation of trans-chalcone using an n-alkyl-polyoxyethylene surfactant based microemulsion was fastest in the system with the PTA (τ = 66 min) and slightly slower without the PTA (τ = 77 min). It was still slower in the two-phase system with a PTA (τ = 114 min) and extremely sluggish without a phase-transfer agent. With n-alkyl β-D-glucopyranoside as the surfactant the conversion was twice as fast than in the former microemulsion systems, but the PTA did not accelerate the reaction further (τ = 35 and 33 min). The epoxidation of vitamin K₃, the second model system, was extremely accelerated. It proceeded a factor of approximately 35 faster in the microemulsion (τ =1.44 min) than in the corresponding two-phase system (τ = 57 min).

Full text of DOI:10.1002/chem.200600550

FULL PAPER
DOI: 10.1002/chem.200600550
Dramatic Enhancement of Enone Epoxidation Rates in Nonionic
Microemulsions
[
b]
[b]
[b]
[a]
Thomas Wielpütz, Thomas Sottmann, Reinhard Strey, Friederike Schmidt, and
[
a]
Albrecht Berkessel*
Abstract: The ability of microemul-
sions to dissolve polar and non-polar
components with a huge internal inter-
face can overcome the reagent incom-
patibilities frequently encountered in
organic reactions. We investigated
model epoxidation reactions of a,b-un-
saturated enones and alkaline hydro-
gen peroxide in different nonionic mi-
croemulsions, both in the presence and
systems. In addition, we defined a time
constant t as a measure for the rate of
turnover. The epoxidation of trans-
chalcone using an n-alkyl-polyoxyethy-
lene surfactant based microemulsion
was fastest in the system with the PTA
(t=66 min) and slightly slower without
the PTA (t=77 min). It was still
slower in the two-phase system with a
PTA (t=114 min) and extremely slug-
gish without a phase-transfer agent.
With n-alkyl b-d-glucopyranoside as
the surfactant the conversion was twice
as fast than in the former microemul-
sion systems, but the PTA did not ac-
celerate the reaction further (t=35
and 33 min). The epoxidation of vita-
min K , the second model system, was
3
extremely accelerated. It proceeded a
factor of approximately 35 faster in the
microemulsion (t=1.44 min) than in
the corresponding two-phase system
(t=57 min).
absence of
a phase-transfer agent
Keywords: enones · epoxidation ·
(
PTA). The obtained reaction profiles
kinetics
·
microemulsions
·
were compared with those for the cor-
responding surfactant-free two-phase
phase-transfer catalysis
Introduction
uids such as DMSO (dimethyl sulfoxide) and DMF (di-
methyl formamide), offering the possibility of solubilizing
both the organic and the inorganic compound. These sol-
vents are excellent media; however, they have three main
drawbacks: they are expensive, toxic and have high boiling
points, which makes them difficult to remove once the reac-
Organic Synthesis lies at the heart of the production of fine
chemicals, pharmaceuticals and other valuable products
from readily available and cheap starting materials. Howev-
er, reagent incompatibility, that is, dramatically different sol-
ubility properties are frequently encountered in organic re-
actions (i.e., inorganic salts and organic substrate). In many
cases, water-soluble reactants such as inorganic salts need to
be reacted with water-insoluble organic compounds. Many
reactions, for instance, the alkaline hydrolysis of esters, oxi-
dative cleavage of olefins or nucleophilic substitution on
benzylhalides with inorganic salts are typical examples. It is
current practice to solve the problem of the pure phase con-
tact by choosing as solvents polar protic or polar aprotic liq-
[1]
tion is completed.
As an alternative approach, the reactants can be dissolved
in two immiscible solvents, and the contact area between
the phases is increased by either intensive mechanical
mixing or better by the use of a phase-transfer agent (PTA).
These PTAs, in most cases quaternary ammonium salts and
crown ethers, act as phase-transfer catalysts (PTCs) and are
widely used in two-phase reactions. Such compounds are ca-
pable of carrying the ionic reactant into the organic phase,
where the low degree of solvation increases the reactivity
remarkably. PTCs have been intensively used for oxidation
[
1–3]
[
a] Dr. F. Schmidt, Prof. Dr. A. Berkessel
Department of Organic Chemistry, University of Cologne
Greinstrasse 4, 50939 Kçln (Germany)
Fax : (+49)221-470-5102
reactions in general.
The catalytic epoxidation of
[4]
enones, in particular the epoxidation of trans-chalcone
using alkaline hydrogen peroxide (Weitz–Scheffer condi-
[5]
tions) as oxidant, is of special interest in this field. Jew
et al. found an enhancement of the enantioselectivity and
the reaction rate in epoxidations of trans-chalcone using
enantiomeric pure PTAs and catalytic amounts of technical
E-mail: berkessel@uni-koeln.de
[
b] Dipl.-Chem. T. Wielpütz, Dr. T. Sottmann, Prof. Dr. R. Strey
Department of Physical Chemistry, University of Cologne
Luxemburger Strasse 116, 50939 Kçln (Germany)
Chem. Eur. J. 2006, 12, 7565 – 7575
ꢀ 2006 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
7565

[
6]
grade surfactants. In 2000, Maruoka and co-workers re-
ported a significant rate enhancement of phase-transfer cat-
alyzed enone epoxidations and alkylations by the combina-
already shown by Boyer and co-workers that this PTA accel-
erates the transformation of enones to epoxides under
Weitz–Scheffer conditions in heterogeneous two-phase sys-
[7]
[5]
tion of a non-chiral PTC and ultrasonic irradiation.
tems. For comparison, the same reaction was performed in
Microemulsions are thermodynamically stable, optically
isotropic mixtures of at least the three components water,
a second nonionic microemulsion based on the rather hydro-
philic nonionic surfactant n-octyl b-d-glucopyranoside
(C G ). The phase behaviour of this rather temperature in-
1
[8,9]
oil and surfactant.
These ternary systems offer various
8
1
nanosized and complex microstructures, with a huge internal
interface that can vary from droplets of oil dispersed in a
continuous water phase over a bicontinuous “sponge” phase
sensitive surfactant was tuned by using a medium-chain al-
cohol as cosurfactant, resulting in the quaternary system
H O–n-octane–C G –1-octanol (C E ). In the second part of
2
8
1
8
0
[10–13]
to water droplets dispersed in a continuous oil phase.
this work, the epoxidation of vitamin K (III) by alkaline hy-
3
Regardless of the structure, the surfactant generates the in-
ternal surface which is positioned as a monolayer between
water and oil. Much effort has been devoted to the utiliza-
tion of these macroscopically homogeneous but microscopi-
drogen peroxide was performed in the nonionic microemul-
sion system H O–toluene–C E , and analyzed kinetically by
UV/Vis measurements.
2
10
8
[14]
cally nanosized two-phase systems as reaction media.
[
15–17]
[18,19]
Nanoparticle designing,
polymerizations,
enzymatic
Results
[20]
reactions and, of course in our interest, organic synthetic
[21]
transformations
are suitable applications of microemul-
Epoxidation of trans-chalcone (I)
sions. These ternary systems have the ability to dissolve a
broad spectrum of water-soluble and water-insoluble com-
pounds. An organic reaction occurs at the very large water–
oil interface and, in contrast to the use of PTAs, the ionic re-
actant is not transported into the oil phase. Additionally,
these solutions are highly dynamic with a surfactant mono-
layer fluctuating on the time scale of less than milliseconds.
This effect, as well as the high local reactant concentrations
inside the water and oil sub-volumes influence and increase
the reaction rates.
The reaction scheme of the epoxidation of trans-chalcone
(I) is shown in Scheme 1. As can be seen in Scheme 1, de-
protonation of H O by NaOH in the aqueous phase deter-
2
2
ꢀ
mines the concentration of the reactive species OOH . Due
[29]
to the fact that the pK of H O is 11.65, the formation of
a
2
2
the hydrogen peroxide anion is favored. The reaction B be-
ꢀ
tween the substrate trans-chalcone (I) and OOH can then
take place at the interfacial area of the microemulsion and
consumes one molar equivalent of hydrogen peroxide. As
already discussed by Boyer and co-workers, both nucleophil-
A number of reactions show enhanced reaction rates in
microemulsions, for example, the oxidation of different hy-
ꢀ
ꢀ
ic reagents OH and OOH were not able to open the epox-
[22]
[5]
drophobic substrates by Caron and co-workers, alkylation
ide ring of rac-II.
[23]
of phenol, nucleophilic sub-
[24]
stitution reactions as well as
catalytic, enantioselective oxi-
[25]
dations of olefins
by Egger
et al. The microemulsion ap-
proach and the PTA approach
can be combined by adding a
specific ionic surfactant to a
microemulsion system, yielding
together the highest reaction
Scheme 1. Weitz–Scheffer epoxidation of trans-chalcone (I), yielding the epoxide rac-II.
[26–28]
rates.
However, only a few
reports have dealt with this
The H O/NaOH/H O –n-octane/trans-chalcone–C E /C E -
2 2 2 10 4 10 5
powerful method so far.
A
H
R
U
G
In our approach, we used this combined method, that is,
using a one-phase microemulsion formulation based on the
well-known nonionic surfactants n-alkyl-polyglycol ether
pseudo-ternary systems is usually studied in T(g) phase dia-
grams at a constant mass ratio a of oil-to-water plus oil,
which is a representative cut through the corresponding
[10,30,31]
(
C E ) with a cationic quaternary ammonium PTA. As a
phase prism.
pseudo-ternary system H O/NaOH/H O –n-octane/trans-
Figure 1 shows a T(g) section of the
i
j
model reaction, we studied the epoxidation of the enone
trans-chalcone (I) by alkaline hydrogen peroxide as a mild,
inexpensive and environmentally benign oxidant. As micro-
emulsion system we used H O–n-octane–C E /C E with
2
2
2
chalcone–C E /C E (-DTAB, 10 mol%) at d=mC10E5
/
1
0
4
10
5
(mC10E5 + mC10E4)=0.225 and a=0.4120, which corresponds
to equal volumes of water and oil. The concentrations of the
solutes in the water phase were c(H O , NaOH)=0.30m and
2
10
4
10
5
and without phase-transfer agent. We employed dodecyltri-
methylammonium bromide (DTAB) as PTA because it was
2
2
of the substrate in n-octane c(trans-chalcone)=0.15m.
The phase boundaries resemble the shape of a “fish-
tail”. It shows a one-phase region (1) which contains a la-
1
[11]
The term “oil” stands for hydrophobic liquids in general.
7566
www.chemeurj.org
ꢀ 2006 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Chem. Eur. J. 2006, 12, 7565 – 7575

Enone Epoxidation
FULL PAPER
investigated without and with DTAB. The reaction composi-
tions are designated by the star in Figure 1 and Table 1.
Figure 2 shows the reaction profiles in the different media
monitored by HPLC. Here, the epoxide yield is shown as a
function of time. The reaction was also performed in the ap-
propriate two-phase system with addition of 10 mol%
DTAB (relative to the substrate concentration). The compo-
sitions and the measurement conditions of the three reac-
tions are compiled in Table 1. The time constants t of all
profiles were calculated as the reciprocal slope of an expo-
nential function fitted to the experimental data and are also
compiled in Table 1.
The use of a microemulsion with DTAB (curve 1) in the
epoxidation of trans-chalcone (I) resulted in a substantial ac-
celeration of the reaction rate compared to both the microe-
mulsion without DTAB (curve 2), and even more compared
to the heterogeneous two-phase system with DTAB (curve
3). Nevertheless, the reaction in the microemulsion without
DTAB proceeded still faster than the reaction in the hetero-
geneous two-phase system with DTAB. In all three systems
the conversion was quantitative after six to ten hours. In
contrast, the product rac-II was not detected in the hetero-
geneous two-phase system without DTAB after t=24 h. As
a measure for the reaction rate a time constant is extracted
2 2 2
Figure 1. Phase diagram of the pseudo-ternary system H O/NaOH/H O –
n-octane/trans-chalcone–C10
and d 10E5 =0.225 containing c(trans-chalcone)=0.15m in the oil phase
and c(NaOH)=0.30 and c(H )=0.30m in the aqueous phase. The star
shows the reaction composition.
4 5
E /C10E (-DTAB, 10 mol%) at a=0.4120
C
A
C
H
T
R
E
U
N
G
A
T
E
N
2 2
O
mellar phase (L ) at higher surfactant mass fractions (open
a
squares). At lower temperatures, a two-phase area (2) exists
where an oil-in-water micro-
A
C
H
T
R
E
U
N
G
emulsion coexists with an oil
2 2 2
Table 1. Compositions of the epoxidation reaction of trans-chalcone (I) in the system H O/NaOH/H O –n-
excess phase. A second two-
phase area (2) exists at higher
octane/trans-chalcone–C10
E
4
/C10E
5
at a=0.4120 and T=18.008C.
¯
Equivalents
c [m]
temperatures where a water-
in-oil microemulsion coexists
No. H O
NaOH trans-chalcone H O
2
NaOH trans-chalcone t [min]
g
dC10E5 DTAB
2
2
2
[a]
1
2
3
2
2
2
2
2
2
1
1
1
0.30
0.30
0.30
0.30
0.30
0.30
0.15
0.15
0.15
66.19
77.06
114.07
0.155 0.225 with
0.155 0.225 without
–
with
a
water excess phase.
[
a]
–
with
Considering the one-phase
region it can be seen that it
shrinks with decreasing surfac-
tant mass fraction g. The point
[a] 10 mol%.
where the phase boundaries meet is referred to as the X-
point or “fishtail” point. This X-point is a reference point
for each system and describes the minimum mass fraction of
surfactant which is necessary for the complete solubilization
˜
of water and oil at a specific temperature (denoted as g˜ , T).
Decreasing g further a three-phase body (3) appears, in
which the microemulsion phase coexists with a water and an
oil excess phase. The X-point of the pure ternary system
[31]
˜
H O–n-octane–C E is located at T = 24.38C. The addi-
2
10
4
tion of NaOH shifts the X-point to lower temperatures. In
our case, this effect was partially compensated by the addi-
tion of the more hydrophilic surfactant C E . We chose the
1
0
5
specific mass ratio of dC10E5 = 0.225 in order to adjust the X-
˜
point temperature at T=188C since organic reactions with
sensitive starting materials (i.e., the decomposition of H O )
2
2
and products should be performed at low temperatures. Fur-
thermore, all following transformations of trans-chalcone (I)
to the epoxide rac-II are carried out at T=188C in order to
avoid different temperature effects on the reaction profiles.
Addition of 10 mol% DTAB as PTA (with respect to the
substrate concentration) does not influence the phase boun-
daries noticeably. The conversion of trans-chalcone (I) was
Figure 2. Reaction profiles for the epoxidation of trans-chalcone (I) to
the epoxide rac-II at T=18.008C, a = 0.4120 in the microemulsion
system
0 mol% (with respect to the substrate concentration) DTAB (full cir-
cles, curve 1), without DTAB (dotted circles, curve 2), as well as the reac-
tion in the two-phase system H O/NaOH/H –n-octane/trans-chalcone
2 2 2 4 5
H O/NaOH/H O –n-octane/trans-chalcone (I)–C10E /C10E with
1
2
2 2
O
with 10 mol% DTAB (open circles, curve 3). Lines shown are guides to
the eye.
Chem. Eur. J. 2006, 12, 7565 – 7575
ꢀ 2006 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemeurj.org
7567

A. Berkessel et al.
from the exponential fit to the experimental data (given in
minutes and seconds). For the microemulsion with DTAB,
without DTAB and of the heterogeneous two-phase system
with DTAB it amounts to t=66, t=77 and t=114 min, re-
spectively. Consequently, the reaction in the microemulsion
with and without PTA is approximately twice as fast as in
the two-phase system with PTA.
plus-water mass fraction of a=0.4120. Figure 3a and b show
the phase diagrams of the system H O/NaOH/H O –n-
2
2
2
octane/trans-chalcone–C G –1-octanol (C E ) at this a and a
8
1
8
0
constant temperature of T=18.008C. The ordinate and the
abscissa mirror the overall C E mass fraction and the over-
8
0
all C G mass fraction, respectively.
8
1
In Figure 3a, the concentrations of trans-chalcone (I) in n-
octane, H O in water and NaOH in water were chosen to
2
2
The H O/NaOH/H O –n-octane/trans-chalcone–C G
A
H
R
U
G
be
(NaOH)=0.30m. In Figure 3b c(trans-chalcone) equals
0.15m, c(H O )=4.50m and c(NaOH)=0.45m.
c(trans-chalcone)=0.15m,
c
A
H
R
U
G
and
2
2
2
8
1
2
2
system: The pseudo-quaternary microemulsion studied con-
tains the four components H O/NaOH/H O (A), n-octane/
c
ACHTREUNG
A
H
R
U
G
ACHTREUNG
2
2
2
2
2
trans-chalcone (B), n-octyl b-d-glucopyranoside
A
H
R
U
G
The phase boundaries in both diagrams resemble the
shape of a “fishtail” with the phase progression 2–3–2 for
8
1
¯
and as cosurfactant 1-octanol (D). The weak temperature
sensitivity of the surfactant C G in this system makes it dif-
low mass fractions of surfactant while for high mass frac-
8
1
¯
ficult to influence the phase behaviour by varying the tem-
perature. Instead, the hydrophobic cosurfactant 1-octanol
tions of surfactant the progression 2–1–2 is observed with in-
creasing amount of 1-octanol. Comparing Figure 3a and b it
is obvious that the X-points coincide well with each other.
Consequently, both reactants H O and NaOH appear to do
(
C E ) was used for tuning the system in the same fashion
8 0
as if the temperature was increased. Considering a four
component system, the phase behaviour has to be represent-
ed in a phase tetrahedron at constant pressure and tempera-
2
2
not affect the phase behaviour noticeably. Note that c
is increased by a factor of 15 from 0.30 to 4.50m.
A
C
H
T
R
E
U
N
G
(H O )
2 2
[32,33]
ture.
The characterization of the phase behaviour is
The reaction profiles within the two microemulsions con-
taining c(H O )=0.30m, c(NaOH)=0.30m in the aqueous
most conveniently done performing two-dimensional sec-
tions through the phase tetrahedron at a constant oil to oil-
A
H
R
U
G
ACHTREUNG
2
2
phase and c(trans-chalcone)=0.15m in the organic phase
were determined. One of them comprises additional
1
0 mol% of DTAB as PTA (again with respect to the sub-
strate concentration) which does not influence the phase be-
haviour remarkably. The composition of both samples is
designated by the star in Figure 3a. The reaction profile of
the system containing c
A
H
R
U
G
A
T
E
N
2
2
the aqueous phase and c(trans-chalcone)=0.15m in n-octane
was monitored at the sample composition exhibited by the
star in Figure 3b. The reaction profiles of the epoxidation in
the different reaction media are shown in Figure 4 while
Table 2 compiles the compositions of the reaction media.
For comparison, the time profile of the reaction in the heter-
ogeneous two-phase systems with 10 mol% of DTAB is also
given. All time constants t of the reactions were obtained as
discussed above and they are compiled in Table 2.
The microemulsion containing 30 equivalents H O with
2
2
respect to the substrate showed the fastest reaction rate and
quantitative conversion after t=150 min (curve 4, t=
2
7 min). The reaction proceeded more slowly in the two mi-
croemulsions with lower peroxide concentrations (curve 5
and 6) while one of them contained 10 mol% DTAB (filled
circles). The time constants t for curve 5 (t=35 min) and 6
(
t=33 min) show no substantial difference in the reaction
rates. In both cases, the conversion of trans-chalcone (I) is
quantitative finished after t=300 min. In fact, all three mi-
croemulsion systems described show a considerable en-
hancement of the reaction rate compared to the two-phase
system with 10 mol% DTAB (t=114 min). In the latter
case, the conversion is not quantitative after t=420 min
(curve 3). Hence, the reaction acceleration in the micro-
Figure 3. Phase diagram of the pseudo-quaternary system H
–n-octane/trans-chalcone–C –C at a=0.4120 and T=18.008C.
a) Containing c(H /NaOH)=0.30m in the aqueous phase and c(trans-
chalcone (I))=0.15m in the oil phase. b) Containing c(H )=4.50m and
(NaOH)=0.45m in the aqueous phase and c(trans-chalcone (I))=0.15m
in the oil phase. The stars indicates the reaction compositions.
2
O/NaOH/
H
2
O
2
8
G
1
8 0
E
A
H
R
U
G
2
O
2
pared with the two-phase system with DTAB. It is three-
fold in the microemulsions both with and without DTAB
using two equivalents of peroxide.
A
H
E
N
2 2
O
c
ACHTREUNG
7568
www.chemeurj.org
ꢀ 2006 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Chem. Eur. J. 2006, 12, 7565 – 7575

Enone Epoxidation
FULL PAPER
The H O/NaOH/H O –toluene/III–C E system: Due to the
2
2
2
10
8
low solubility of vitamin K (III) in n-alkanes, the aromatic
3
oil toluene was chosen as organic solvent in the pseudo-ter-
nary system H O/NaOH/H O –toluene/III–C E . The terna-
2
2
2
10
8
ry base system H O–toluene–C E was investigated previ-
2
10
8
[34]
ously. It was shown that the already known phase behav-
iour of the systems H O–n-alkane–C E is transferable to ter-
2
i
j
nary systems comprising H O–toluene–C E .
2
10
8
Figure 5 shows a T(g) phase diagram of the system H O/
2
NaOH/H O –toluene/III–C E at constant a=0.4120. The
2
2
10
8
concentrations of H O and NaOH with respect to the water
2
2
phase and vitamin K (III) with respect to the oil phase are
3
c
A
H
R
U
G
A
H
R
N
A
H
R
U
G
2
2
spectively. Because the volumes of oil and water are not
equal at a=0.4120, the molar ratio of III to NaOH to H O2
2
is 1 to 3.7 to 37.3.
The phase diagram shows the typical “fishtail” behaviour
Figure 4. Reaction profiles for the transformation of trans-chalcone (I) to
with an X-point at g˜ ꢁ0.12 and Tꢁ148C and a pronounced
˜
the epoxide rac-II at T=18.008C in the microemulsion system H
NaOH/H –n-octane/trans-chalcone–C –C with and without
0 mol% DTAB (with respect to the substrate concentration). The filled
triangles (curve 4) show the conversion in the microemulsion system
without DTAB containing c(H )=4.50m and c(NaOH)=0.45m in the
2
O/
lamellar phase L at slightly higher mass fractions of surfac-
a
2
O
2
8
G
1
8 0
E
tant.
1
The reaction in the microemulsion, the composition of
which is indicated by the star in Figure 5 (g=0.13 and T=
4.008C) was to fast to be monitored by GC. The color
A
H
R
U
G
2
O
2
ACHTREUNG
aqueous phase and c(trans-chalcone)=0.15m in the oil phase. The filled
and dotted circles show the profile in the microemulsion containing
1
change from the yellow vitamin K (III) to the colorless ep-
3
c
A
C
H
T
R
E
U
N
G
(H
2
O
2
)=0.30m and c(NaOH)=0.30m in the aqueous phase and c(trans-
A
C
H
T
R
E
U
N
G
oxide rac-IV points to a complete conversion after a few mi-
nutes. No substrate (III) could be detected after t=4 min.
Throughout the reaction the system was in the one-phase
area, indicating low impact of the substrate or H O on the
chalcone)=0.15m in n-octane with and without DTAB, respectively. The
open circles exhibit the reaction course of the two-phase system contain-
ing c
A
C
H
T
R
E
U
N
G
(H
2
O
2
)=0.30m and c(NaOH)=0.30m in the aqueous phase and
A
H
R
U
G
c(trans-chalcone)=0.15m in n-octane. Lines shown are guides to the eye.
2
2
phase behaviour.
In order to slow down the
reaction rate the aqueous con-
2 2 2
Table 2. Compositions of the epoxidation reaction of trans-chalcone (I) in the system H O/NaOH/H O –n-
octane/trans-chalcone–C
8
G
1
–C
8
E
0
at a=0.4120 and T=18.008C.
centrations of H O2 and
NaOH were reduced to
2
Equivalents
NaOH trans-chalcone
c [m]
mC8 G1
mC8 E0
No.
H
2
O
2
H
2
O
2
NaOH trans-chalcone t [min]
P
P
DTAB
m
m
c
c
0
A
T
E
N
(H O )=0.36m
and
or
2
2
4
5
6
3
30
2
2
3
2
2
2
1
1
1
1
4.50
0.30
0.30
0.30
0.45
0.30
0.30
0.30
0.15
0.15
0.15
0.15
27.44
35.22
33.13
0.154 0.06 without
A
H
R
U
G
0.03
[
a]
0.154 0.06 with
0.154 0.06 without
.012m, respectively. Figure 6
[
a]
shows a series of T(g) phase
2
114.07
–
–
with
diagrams of the system H O/
2
[
a] 10 mol%.
NaOH/H O –toluene/III–C E
8
2
2
10
at a=0.4120 containing differ-
ent concentrations of H O ,
2
2
Epoxidation of vitamin K3
A
H
R
U
G
NaOH and III. As expected, the phase boundaries resemble
the shape of a “fishtail”, and all systems exhibit the typical
X-point.
The epoxidation of III to the epoxide rac-IV is shown in
Scheme 2. The reaction of III to the corresponding epoxide
rac-IV requires the same deprotonation of H O as already
Phase diagram A shows the ternary system H O–toluene–
2
C E without H O , NaOH and III. In phase diagrams 7, 8
2
2
10
8
2
2
shown in Scheme 1. The subsequent reaction between the
enone III and OOH takes place at the interfacial area.
and 9 the concentrations of H O in the aqueous phase and
2 2
ꢀ
III in toluene are c
spectively. Furthermore, the concentration of NaOH is in-
creased from 9, 8 and 7 to c(NaOH)=0.012, 0.03 and 0.06m,
A
H
R
U
G
A
T
E
N
(III)=0.15m, re-
2
2
AHCTREUNG
respectively. As can be seen from Figure 6, low concentra-
tions of the substrate and alkaline hydrogen peroxide shift
the X-point only slightly to lower temperatures. Comparison
with Figure 5 reveals that even the strong increase of the
H O and NaOH concentrations to c(H O )=4.50m and
A
H
R
U
G
2
2
2 2
˜
c
A
H
R
U
G
Scheme 2. Reaction scheme for the epoxidation of III to the epoxide rac-
IV.
˜
(pure ternary system) to Tꢁ148C while the mass fraction of
Chem. Eur. J. 2006, 12, 7565 – 7575
ꢀ 2006 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemeurj.org
7569

A. Berkessel et al.
The concentration of H O in the aqueous phase, and III in
2
2
toluene were set at c
whereas the concentration of NaOH was varied: c-
(NaOH)=0.012, 0.03 and 0.06m. Each profile was moni-
A
H
R
U
G
A
T
E
N
(III)=0.15m,
2
2
AHCTREUNG
tored in the one-phase region just in front of the lamellar
phase area at g=0.15 and at the temperature of the X-point
˜
of Tꢁ24.008C (23.50, 22.708C) for c
A
H
R
U
G
0
.06m). The transformation was also performed in the ap-
propriate two-phase system H O–toluene at T=22.708C
2
where the concentration of III in toluene and of H O and
2
2
NaOH in water are c
A
H
R
U
G
A
H
R
U
c
ACHTREUNG
(NaOH)=0.06m, respectively. In the three microemulsion
systems the UV transmittance of III was continuously meas-
ured during the reaction. Figure 7 shows the transmittance
Figure 5. Phase diagram of the system H
system at a=0.4120 containing c(H
.45m in the aqueous phase and c(III)=0.15m in the oil phase. A signifi-
2
O/NaOH/H
2
O
2
–toluene/III–
C
10
E
8
A
H
R
U
G
2
O
2
)=4.50m and c
ACHTREUNG
(NaOH)=
0
ACHTREUNG
cant lamellar phase exists in the one-phase region. The reaction composi-
tion and temperature is designated by the star.
1
Figure 7. Reaction profiles (curves 7, 8 and 9, axis: T/T ) for the transfor-
mation of III to the epoxide rac-IV measured in the system H
–toluene/III–C10 by UV/Vis spectroscopy. The wavelength which
transmittance has been observed as a function of time is l=415 nm (dcell
1 mm). Curves 7, 8 and 9 correspond to conditions specified in Table 3
2
O/NaOH/
H
2
O
2
E
8
=
and Figure 6. Curve 10 shows the normalized reaction profile for the for-
mation of the epoxide rac-IV in the heterogeneous two-phase system
with
axis: epoxide/epoxide ) at T=22.78C. The dashed lines (7–9) and the
solid line (10) shown are guides to the eye.
c
toluene
A
H
R
U
G
A
H
E
N
(NaOH)=0.06m and cH2O
A
H
R
U
G
2 2
(H O )=0.36m
Figure 6. Phase diagrams of the
system at a=0.4120. In diagram A the system contains no substrate. Dia-
gram 7, 8 and 9 contain c(III)=0.15m in toluene and c(H )=0.36m
and c(NaOH)=0.012, 0.03 and 0.06m, respectively, in water. The X-point
H
2
O/NaOH/H
2
O
2
–toluene/III–C10
E
8
1
(
A
H
R
U
G
A
H
R
U
G
2 2
O
ACHTREUNG
drops to some extend in temperature while the concentration of NaOH
is increased. The reaction compositions are designated by the star in 7, 8
and 9.
normalized onto the transmittance at quantitative transfor-
mation (axis T/T ) as function of time. On the other hand,
1
the transformation of III in the two-phase system was meas-
ured by GC. Consequently, this reaction profile was given
by data points that are assigned to the axis epoxide/epox-
surfactant at the X-point stays approximately constant at g˜
1
ꢁ
0.12. The shift of the phase behaviour to lower tempera-
ide of Figure 7, that is, the normalized yield of the epoxide.
tures is due the effect that H O molecules have to hydrate
As discussed above, all time constants were obtained by fit-
ting an exponential function to the experimental data.
Table 3 summarized the sample compositions and reaction
conditions of the reaction shown in Figure 7.
The reaction was extremely fast in all microemulsion sys-
tems. Using 50 mol% NaOH with respect to the substrate
2
the starting materials and thus are not available for the hy-
[35]
dration of the surfactant head groups.
The epoxidation of III in the microemulsion systems was
monitored by UV/Vis measurements, following the transmit-
tance of the incident light at l=415 nm, as described in the
Experimental Section. Three reaction profiles were recorded
at a constant a=0.4120, using the one-phase microemulsion
H O/H O /NaOH–toluene/III–C E as reaction medium.
concentration (c
quantitative after t=5 min. With 25 mol% NaOH
(c(NaOH)=0.03m, curve 8), the reaction was nearly as fast
A
H
R
U
G
AHCTREUNG
2
2
2
10
8
7570
www.chemeurj.org
ꢀ 2006 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Chem. Eur. J. 2006, 12, 7565 – 7575

Enone Epoxidation
FULL PAPER
Table 3. Compositions of the epoxidation reaction of III in the system
As can be seen in Figure 2 (curve 2) a significant increase
in the reaction rate was obtained by using the nonionic mi-
croemulsion system H O/NaOH/H O –n-octane/trans-chal-
H
2
O/NaOH/H
Equivalents
NaOH III
2 2 8
O –toluene/III–C10E at a=0.4120.
c [m]
2
2
2
No.
H
2
O
2
H
2
O
2
NaOH III
t [min]
g
T [8C]
cone–C E /C E . The total surfactant mass fraction of g=
1
0
4
10
5
7
8
9
3
3
3
3
0.50
0.25
0.10
0.50
1
1
1
1
0.36
0.36
0.36
0.36
0.06
0.03
0.012
0.06
0.15
0.15
0.15 19.05
0.15 56.57
1.44
3.51
0.15 22.70
0.15 23.50
0.15 24.00
0
.155 leads to a significantly larger total interfacial area,
which in turn results in an enhancement of the reaction rate
Figure 2, curve 2). The observation that the reaction rates
are different in the heterogeneous two-phase system with
0 mol% DTAB and in the microemulsion indicates that in
(
1
0
–
22.70
1
and the transformation was completed after t=12 min. With
0 mol% NaOH (c(NaOH)=0.012m, curve 9) the reaction
still proceeded extremely well, but the quantitative product
was obtained after t=90 min. This result is in line with the
time constants t which increase from t=1.44, 3.51 to
the rate-limiting step, close contact between the two reac-
tants is facilitated. As a consequence, the epoxidation of
trans-chalcone (I) proceeds very quickly and efficiently.
1
ACHTREUNG
Considering the model S 2 reaction between 4-tert-butyl-
N
benzyl bromide and potassium iodide the situation can be
[27]
19.05 min for curves 7, 8 and 9, respectively.
different.
They found that the conversion within a two-
In contrast to the above results, in the two-phase system
phase system with addition of a PTA is just as fast as in a
microemulsion system with PTA. In this case the total inter-
facial area does not determine the reaction rate and one
may assume a fast and efficient extraction equilibrium,
whereby the “chemical” reaction itself is the rate determin-
ing step.
H O/NaOH/H O –toluene/III
without
C E
10
with
2
2
2
8
c
A
C
H
T
R
E
U
N
G
(NaOH)=0.06m and c
ACHTREUNG
(H O )=0.36m in the aqueous phase
2
2
and c(III)=0.15m in toluene at T=22.708C, the conversion
ACHTREUNG
to the product proceeds sluggishly. The conversion of III to
the epoxide rac-IV is not quantitatively after t=180 min
(
t=57 min). Thus, the corresponding reaction rate in the
As can be seen in Figure 2, addition of 10 mol% DTAB
to the microemulsion system further increases the reaction
rate (curve 1). The amount added is so low (0.24 wt%) that
the total interfacial area between water and n-octane is not
enhanced significantly. Hence, the effect of the surface en-
hancement can be neglected while the function as PTA must
be taken into account. Furthermore, this result supports the
assumption that bringing the two reactants in close contact
to each other (either by increasing the interfacial area or by
using a PTA) is the rate-limiting, that is, and not the “chemi-
cal” reaction between the enone and the oxidant.
microemulsion is a factor of approximately 35 faster than in
the heterogeneous two-phase system.
Discussion
Epoxidation of trans-chalcone (I)
The solubility of trans-chalcone (I) in water and that of hy-
drogen peroxide and sodium hydroxide in n-octane is ex-
tremely low. Accordingly, the epoxidation reaction can only
take place at the water–n-octane interface within the two-
phase system. Due to the fact that the interfacial tension be-
tween water and n-octane is very high (~50 mNm ), the in-
terfacial area, even with intensive mechanical stirring, is ex-
tremely small. No conversion of the enone I to the epoxide
rac-II was obtained after 24 h.
The reaction proceeds faster in the similar nonionic mi-
croemulsion system H O–n-octane–C G –C E , based on the
2
8
1
8
0
rather hydrophilic surfactant n-octyl b-d-glucopyranoside,
and using 1-octanol as cosurfactant. As can be seen in
Figure 4, the conversion to the epoxide is slowest for the
heterogeneous two-phase system (curve 3) as already dis-
cussed above, faster in the microemulsion with and without
10 mol% DTAB (curve 5 and 6, respectively), and fastest
when a large excess of H O was employed (curve 4). With
ꢀ
1
Furthermore, it is not surprising that the reaction in the
two-phase system without PTA is slower than in the system
with 10 mol% of DTAB. As can be seen in Figures 2 and 4
2
2
equal concentrations of oxidant and base, the reaction pro-
ceeds faster in the C G /C E system without DTAB
(
curve 3), the epoxidation proceeds reasonably fast under
8
1
8
0
these conditions. DTAB acts simultaneously as ionic surfac-
tant and as PTA by carrying the anionic reactant into the oil
phase. The ionic surfactant decreases the interfacial tension
between water and n-octane. Therefore, the interfacial area
where the contact between the reagents is facilitated in-
creases noticeably. In addition, the positively charged
DTAB which adsorbs at the oil–water interface may well at-
tract the negatively charged hydrogen peroxide anion. Due
to DTAB acting as PTA, a favorable extraction equilibrium
is established, namely, the equilibrium between the PTA in
the water and in the oil phase, carrying the hydroperoxide
(Figure 4, curve 6) than in the C E /C E system without
10 4 10 5
DTAB (Figure 1, curve 2). This behaviour is reflected in the
time constants of the reaction profiles which are t=77 min
for the C E /C E based systems and more than twice as
1
0
4
10
5
fast (t=33 min) for the C G /C E based system, respective-
8
1
8
0
ly. In both systems, the reactions were conducted under very
similar conditions, only different surfactants and surfactant
amounts were used. This indicates a correlation of the reac-
tion rate with the specific interfacial area on one hand,
which is mainly determined by the amount of surfactant and
cosurfactant in the system and the molecular composition of
the interfacial film on the other hand. The specific interfa-
anion. Once carried into the oil, the nucleophilic reagent
ꢀ
ꢀ1
(
OOH ) becomes poorly solvated, and thus highly reactive.
cial area, SV , which is the area created by the surfactant
Chem. Eur. J. 2006, 12, 7565 – 7575
ꢀ 2006 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemeurj.org
7571

A. Berkessel et al.
and the cosurfactant molecules can, as a first approximation,
be calculated as shown in equation (1)
the larger interfacial area. Most likely, the composition of
the interfacial film and the molecular structures of the sur-
factants give rise to considerable differences in the reaction
rates.
[32]
X
X
S
V
aC
vC
aD
vD
¼
ꢀC,i
þ
ꢀD,i
ð1Þ
The very polar structure of C
the dielectrical constant at the interface, compared with the
system containing C10 . This effect was already dis-
covered by Drummond et al. for micelles of sugar-based and
G causes a difference in
8 1
where a and a are the areas and v and v the volumes of
E /C10E
4 5
C
D
C
D
the surfactant and cosurfactant molecules, respectively, fC,i
and fD,i are the overall volume fractions of the surfactants
and cosurfactants in the interfacial layer. The molecular
areas and volumes of the surfactant and cosurfactant mole-
cules and their overall volume fractions in the internal inter-
[37]
of ethoxylate-based surfactants. The conversion of trans-
chalcone (I) to the corresponding epoxide rac-II proceeds
via a charged transition state in which the epoxide ring clo-
[38]
sure is not yet completed (Figure 1)
(and references
[32,36]
face are given in Table 4.
The total interfacial areas be-
therein). It is well known that charged transition states are
stabilized by polar solvents. Therefore, the reaction proceeds
faster the higher the polarity of the solvent is. The same
holds true when one compares the epoxidation reaction in
sugar-based and ethoxylate-based microemulsion systems.
Due to the fact that the reaction takes place at the interfa-
cial film, the high polarity of the surface stabilizes the charg-
ed transition state and accelerates the reaction when the car-
bohydrate-surfactant is employed. Otherwise, as in case of
Table 4. Molecular areas and volumes of the surfactant and cosurfactant
molecules.
2
3
Surfactant
a
C
[Š ]
n
C
[Š ]
C
C
C
C
10
10
10
E
E
E
4
5
8
52.8
579
58.9
77.1
52.0
646
841
429
8
G
1
2
3
the C E /C E system, the reaction proceeds more slowly.
10 4 10 5
Cosurfactant
a
D
[Š ]
v
D
[Š ]
As can be seen by comparison of curves 5 and 6 in
Figure 4, 10 mol% of DTAB does not influence the course
of the reaction noticeably. This is surprising because an en-
hancement of the reaction rate was observed in the nonionic
C E /C E system. However, it may be assumed that the al-
8 0
C E
29.3
260
tween water and oil are compiled in Table 5. Therefore, the
monomeric solubilities of the surfactants and cosurfactants
in water and oil have been taken into account.
1
0
4
10
5
ready very polar surface of the C G -based systems is not
8
1
[
31,34]
polarized further. Furthermore, the conversion in the C G -
8 1
ꢀ
1
2
ꢀ1
The surface area increases from SV = 122 m mL in
based microemulsion is already very rapid and for that
reason, the effect will be extremely small compared to the
“background” reaction.
ꢀ
1
2
ꢀ1
the C E /C E system to SV =212 m mL in the C G /
10
4
10
5
8
1
C E system. DTAB was neglected in the calculation of the
8
0
total specific interfacial area due to its considerably low
amount in the solution. Thus, we conclude that the larger in-
terfacial area of the C G /C E system in comparison with
Epoxidation of vitamin K3
8
1
8
0
the C E /C E system is associated with the observed en-
Because the solubility of vitamin K in water and that of hy-
10
4
10
5
3
hancement of the reaction rate of a factor slightly higher
drogen peroxide and sodium hydroxide in toluene is also
low, one can assume that the epoxidation reaction takes
place only at the water–toluene interface, too. However, the
ꢀ
1
than two. However, the total interfacial area SV , as dis-
cussed above, is not twice as high, and hence, the enhance-
ment of the reaction rate cannot be explained exclusively by
[39]
[40]
small solubility of toluene in water and water in toluene
results in a slow conversion of
III (Figure 7, curve 10). The re-
action turns into completion
after t ꢁ360 min and the time
constant of the reaction is t=
ꢀ
1
Table 5. Summary of the different reaction profiles including the total interfacial area SV and the time con-
stants t of the fitted exponential functions.
No.
System
DTAB
0 mol%
Interface/
t [min]
Equivalents
2
ꢀ1
1
A
H
R
U
]
H
2
O
2
NaOH
Substrate
5
7 min. This is in contrast to
1
2
3
4
5
6
n/a
H
H
H
H
H
H
H
2
2
2
2
2
2
2
O/n-octane/C10
O/n-octane/C10
O/n-octane
E
E
4
4
/C10
/C10
E
E
5
5
with
without
with
without
with
without
without
122
122
n/a
212
212
212
n/a
66.19
77.06
114.07
27.44
35.22
33.13
2
2
2
30
2
2
2
2
2
3
2
2
2
1
1
1
1
1
1
1
the absence of any conversion
of trans-chalcone (I) in the
two-phase system H O/NaOH/
O/n-octane/C
O/n-octane/C
O/n-octane/C
O/n-octane
8
8
8
G
G
G
1
/C
/C
/C
8
8
8
E
E
E
0
0
0
2
H O –n-octane/trans-chalcone.
1
1
2
2
The addition of C E to the
1
0
8
no conv.
2
system H O/NaOH/H O –tol-
2
2
2
uene/III changes the situation
substantially. As can be seen in
Figure 7 curves 7, 8 and 9, the
reaction did take place quanti-
tatively within t=5, 12 and
n/a
7
8
H
H
H
H
H
2
2
2
2
2
O/toluene/C10
O/toluene/C10
O/toluene/C10
O/toluene/C10
O/toluene
E
8
8
8
8
without
without
without
without
without
55
74
74
74
n/a
<1.44
1.44
3.51
19.05
56.57
37.2
3.70
0.50
0.25
0.10
0.50
1
1
1
1
1
E
E
E
3
3
3
3
9
1
0
7572
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ꢀ 2006 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Chem. Eur. J. 2006, 12, 7565 – 7575

Enone Epoxidation
FULL PAPER
9
0 min, respectively. This is in accordance with their time
rather polar interfacial area generated by the surfactant
C E is also of minor importance.
constants t=1.44, 3.51 and 19.95 min. The conversion rate
decreased with the concentration of sodium hydroxide (c=
1
0
8
0.06, 0.03 and 0.012m). This observation indicates that the
concentration of NaOH is decisive for the reaction rate.
Acting as a “catalyst”, the concentration of base mainly de-
termines the reaction rate. Compared with the conversion
without surfactant and 50 mol% base (t=57 min, curve 10),
the conversion of III is a factor of approximately 35 faster
than in the corresponding microemulsion system (Figure 7,
curve 7).
Conclusion
The reaction between trans-chalcone (I) and the alkaline hy-
drogen peroxide proceeds at an appreciable rate in nonionic
microemulsions based on H O, n-octane and C E /C E or,
2
10
4
10
5
alternatively, C G and C E . PTC was effective in the heter-
8
1
8
0
ogeneous two-phase system as well as in the C E /C E
5
1
0
4
10
Table 5 summarizes the total interfacial areas between
water–toluene, calculated by Equation (1), and by taking
based systems. In general, the reaction proceeded fastest in
the systems based on the carbohydrate surfactant. This is
probably due to the fact that the charged intermediate in
the reaction cycle is stabilized better within the very polar
interfacial area. Furthermore, the specific interfacial area is
larger than that in the ethoxyethylate-based systems. More-
over, we found that the reagents NaOH, H O and trans-
chalcone (I) did not show a considerable impact on the
phase behaviour of the carbohydrate surfactant based
system. For this reason, these nonionic microemulsions are
suitable for large scale applications.
[34]
into account the monomeric solubility of C E in toluene.
1
0
8
The specific interfacial area for the system containing g=
ꢀ
1
2
ꢀ1
0
0
.13 is SV =55 m mL and of the systems containing g=
ꢀ
1
2
ꢀ1
.15 is SV =74 m mL . Compared with the values calcu-
2
ꢀ1
lated for the C E /C E (122 m mL ) or the C G /C E
10
4
ꢀ1
10
5
8
1
8
0
2
2
2
system (177 m mL ), it is not possible to explain the rapid
reaction rate by the interfacial area alone. In addition, the
interfacial area is less polar than that of the C G -based one,
8
1
but only slightly more polar than that of the C E /C E -
1
0
4
10
5
based surfactant. Consequently, the b-peroxy
A
H
R
U
G
The reaction between vitamin K , hydrogen peroxide and
3
resulting from the addition of hydroperoxide to III will not
catalytical amounts of base proceeded strikingly fast in the
system H O, toluene and C E . We found a quantitative
be stabilized significantly better by the C E interfacial
1
0
8
2
10
8
layer compared with the interface of the C G /C E and
conversion of vitamin K3 after t=5 min (50 mol% base)
8
1
8
0
C E /C E .
whereas the reaction in the heterogeneous two-phase system
1
0
4
10
5
However, microemulsion formulations with strongly pene-
trating “polar” oils as toluene have been thoroughly investi-
H O–toluene is quantitative after t ꢁ6 h. The time constants
2
reveal that the conversion in the latter system is approxi-
mately 35-fold slower than in the corresponding microemul-
sion.
[34]
gated. It was found that the mass fraction of monomeric-
dissolved C E in toluene is 15.6 wt%. The molecular struc-
10
8
ture of C E is rather similar to the structure of cyclic poly-
Both results are of practical interest for organic synthesis
where the reagent incompatibility is frequently encountered.
Transfer of this oxidation methodology to further enones is
currently under investigation.
10
8
oxyethylenes (crown ethers) which, in turn, are known to
act as PTAs. This leads to the conclusion that n-alkyl-poly-
oxyethylene-based surfactants such as C E have a reasona-
1
0
8
ble extraction equilibrium in the organic phase. The surfac-
tant carries—depending on the quality of C E as PTA—
1
0
8
the reactive species in the organic phase and, hence, the re-
action rate is increased appreciably. This “crown ether
effect” is less pronounced in non-polar oils such as n-alkanes
since under these conditions, the monomeric solubility is
only in the dimension of 2 wt%. Nevertheless, this point is
not sufficient to explain the striking acceleration of the reac-
tion rate compared to the conversion of trans-chalcone (I).
Toluene is not only crucial for the reaction rate due to the
monomeric solubility of the surfactant, but rather the pene-
tration into the interfacial film is decisive for the reaction
rate. It appears that the penetration of toluene brings the re-
ExperimentalSection
Materials: The surfactants polyoxyethylene n-alkylethers (C
and C10 were purchased from Nikko Chemicals (Tokyo,
Japan) and Fluka (Buchs, Switzerland), respectively (> 98% purity in all
cases). n-Octyl b-D-glucopyranoside (C ) was obtained from Bachem
Bubendorf, Switzerland) with a purity > 99%. The phase-transfer agent
i j
E ), namely
C
10
E
4
, C10
E
5
E
8
8
G
1
(
dodecyltrimethylammonium bromide (DTAB), 2-methyl-1,4-naphthoqui-
none (III) and trans-chalcone were purchased from Fluka (Buchs, Swit-
zerland) with a purity of > 98%. As oils, n-octane from Fluka (Buchs,
Switzerland) and toluene from Sigma-Aldrich (Milwaukee, USA) with a
purity of > 99.5 and > 99.8%, respectively, were used. The cosurfactant
1
8 0
-octanol (C E ) was purchased from Sigma-Aldrich (Milwaukee, USA)
actants closer to each other compared with the H O–n-
2
with a purity of > 99.4%. Water was double-distilled using a quartz
column. Sodium hydroxide with a purity of > 99% and a 30% w/w solu-
tion of hydrogen peroxide were purchased from Merck (Darmstadt, Ger-
many). All components were used without further purification.
octane–C E /C E and the H O–n-octane–C G –C E sys-
10
4
10
5
2
8
1
8
0
tems. This effect increases the reaction rate dramatically as
a closer contact of the substrates is provided over the total
interfacial area.
Phase diagrams: Meaningful experiments on microemulsions can only be
conducted if the phase behaviour is well known. Thus, we studied at first
the phase behaviour of all microemulsions used as reaction media. There-
by the phase behaviour is studied in two different ways. While for the
temperature dependent ternary (i.e., pseudo-ternary) systems the isople-
thal (constant composition) method is used, the temperature invariant
The above two aspects are crucial for the rate enhance-
ment. The very strong penetration is assumed to cause an
enhancement of the reaction rate, while the influence of the
monomeric solubility of C E is rather secondary. The
1
0
8
Chem. Eur. J. 2006, 12, 7565 – 7575
ꢀ 2006 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemeurj.org
7573

A. Berkessel et al.
quaternary (i.e., pseudo-quaternary) systems are studied at isothermal
conditions. Accordingly the phase diagrams of the ternary systems are
determined as a function of temperature and the overall surfactant mass
fraction. The polar component (A), the non-polar component (B), the
For the two-phase reaction, a solution of trans-chalcone (I) (46.9 mg,
1.00 equiv, 225 mmol) in n-octane (1.50 mL) and an aqueous solution
(1.50 mL) containing hydrogen peroxide (30% aqueous solution;
37.2 mL, 15.3 mg, 2.00 equiv, 450 mmol) and sodium hydroxide (18.0 mg,
2.00 equiv, 450 mmol) were combined. After a given time 100 mL samples
of the organic phase were withdrawn and the reaction was stopped by ad-
dition of aqueous sodium thiosulfate solution (excess, to ensure complete
reduction of hydrogen peroxide). The organic phase was dried over mag-
nesium sulfate, and the crude product was purified by flash chromatogra-
phy (c-hexane/diethyl ether 9:1). The course of the reaction was moni-
tored by HPLC.
i j
nonionic surfactants C E (C) and, if required, the PTA DTAB were
weighed into test tubes which were then sealed with polyethylene stop-
pers. The occurring phases were investigated at a constant sample com-
position and as a function of temperature in a water bath with a tempera-
ture control of DT
phases are studied by visual inspection of both transmitted and scattered
light. Using crossed polarizers the existence of anisotropic phases, as for
=
ꢂ0.02 K. The number and kind of coexisting
a
example, the lamellar phase (L ) can be detected. To characterize fixed
compositions, it is useful to define the mass fraction of the non-polar
component in the mixture of the polar and non-polar component
II: The epoxidation of III with alkaline hydrogen peroxide was per-
formed in the microemulsion H
system H O–toluene. To this end, stock solutions of the substrate III in
toluene (0.15m) and of NaOH (0.12, 0.06, 0.024 and 0.90m) and H
2 8
O–toluene–C10E and in the two-phase
2
2
O
2
m
B
(0.72 and 9.00m) in water were prepared. Sodium hydroxide and hydro-
gen peroxide were used in different ratios, whereas the concentration of
a ¼ m
þ m
,
ð2Þ
ð3Þ
ð4Þ
A
B
III in toluene was kept constant at c
croemulsion the surfactant C10 was added and the influence of the re-
actants on the phase behaviour was determined.
In the microemulsion containing c(H )=4.50 and c
the aqueous phase, the reaction was carried out in the one-phase region
at T=14.008C. In the microemulsion systems containing c(III)=0.15m,
(H )=0.36m and c(NaOH)=0.06m (0.03, 0.12m) in the aqueous
phase, the substrate conversion was investigated at T=22.708C (23.50,
4.008C). The course of the reaction was monitored by measuring the
transmittance of the incident light through the microemulsion at l=
15 nm where III exhibited a very low transmittance and the product III
A
H
R
U
G
E
8
the overall mass fraction of the surfactant and cosurfactant
P m
þ
P m
D
A
H
R
U
G
2
O
2
A
H
R
U
G
C
g ¼
,
m
total
AHCTREUNG
c
A
H
R
U
G
2
O
2
ACHTREUNG
and the mass fraction of one surfactant in the surfactant mixture
2
m
D
d ¼ m
:
C
þ m
D
4
epoxide rac-IV was almost transparent. UV/Vis measurements were per-
formed with a Perkin Elmer Lambda 19 spectrophotometer. For temper-
ature control, the cell (of 1 mm optical pathway) was placed in a thermo-
stated cell holder with an accuracy of DT=0.028C.
The amount of all starting materials is given in molar concentrations and
of DTAB in mol% with respect to the molar amount of the substrate.
Thereby it is assumed that the concentration of DTAB is so small that
the total interfacial area between water and n-octane is not enhanced
considerably.
Product isolation (reaction conditions according to Figure 7, curve 7) was
performed as follows: The reaction was stopped at t=5 min by the addi-
tion of a large excess of ethyl acetate and water. The phases were sepa-
rated and the aqueous phase was extracted with ethyl acetate. The com-
bined organic phases were evaporated, and the crude product was puri-
fied by flash chromatography (ethyl acetate/c-hexane 3:1). The 2,3-
epoxy-2-methyl-1,4-naphthoquinone (rac-IV) was isolated in 94% yield.
To determine the phase diagrams of the quaternary temperature invari-
ant systems all components were weighed into a test-tube as stated
above. The samples were placed in a water bath at constant temperature
T = 18.00ꢂ0.028C. When temperature equilibrium was reached, the
stopper was lifted and the mixture was titrated with the cosurfactant
8 0
C E (D) using a calibrated microliter syringe. The amount added was
Two-phase reaction conditions: III (38.7 mg, 1.00 equiv, 225 mmol) and di-
phenyl ether (internal standard) (38.3 mg, 1.00 equiv, 225 mmol, 35.7 mL)
were dissolved in toluene (1.50 mL) at 22.708C. After addition of sodium
hydroxide (4.50 mg, 0.50 equiv, 113 mmol) and hydrogen peroxide
controlled by weight with an accuracy of Dm = ꢂ0.001 g. After stirring,
the system was allowed to equilibrate and the occurring phases were
monitored. The composition of these quaternary systems was character-
ized by Equations (2), (3) and (4).
(
68.9 mL, 76.5 mg, 3.00 eq, 675 mmol) in water (1.85 mL) the reaction was
Chemicalreactions : Two different epoxidation reactions were carried out
as follows:
stirred for three hours. After a given time 100 mL samples of the organic
phase were withdrawn. The reaction was stopped by the addition of an
aqueous sodium thiosulfate solution. After drying over magnesium sul-
fate, the organic phase was analyzed by GC.
I: The epoxidation of the a,b-unsaturated enone trans-chalcone (I) with
alkaline hydrogen peroxide was performed in various microemulsions
and in heterogeneous two-phase systems in test tubes using vigorous agi-
tation. Different ratios of the substrate, of the base and of hydrogen per-
oxide were employed. To this end, stock solutions of the substrate I
(
9
0.15m) in n-octane and of NaOH (0.60 and 0.90m) and H
.00m) in water were prepared. If required, the surfactants C10
and DTAB or analogously C , C and DTAB, were added. The influ-
2 2
O (0.60 and
4 5
E , C10E
8
G
1
8 0
E
Acknowledgements
ence of the reactants on the phase behaviour of the corresponding micro-
emulsion was determined. The reactions were all carried out at T=
This work was supported by the “Fonds der Chemischen Industrie”. We
wish to thank Verena Posselt for experimental assistance in the early
stage of the present work.
1
8.008C.
Thereby it was assured that the microemulsion system stayed in the one-
phase state during the complete course of the reaction. After a given
period of time, samples were withdrawn and the reaction was stopped by
addition of aqueous sodium thiosulfate (excess, to ensure complete re-
duction of hydrogen peroxide). The reaction mixture was evaporated to
dryness, and the crude product was purified by flash chromatography
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7574
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ꢀ 2006 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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Received: April 18, 2006
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81.
Published online: September 6, 2006
Chem. Eur. J. 2006, 12, 7565 – 7575
ꢀ 2006 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemeurj.org
7575