High frequency ultrasound as a tool for elucidating mechanistic elements of cis-cyclooctene epoxidation with aqueous hydrogen peroxide

Article abstract of DOI:10.1016/j.ultsonch.2018.12.038

The use of high frequency ultrasound (800 kHz) highlights the non-radical character of the cis-cyclooctene epoxidation mediated by H₂O₂ and H₂WO₄. Combination of moderate mixing brought by the ultrasonic irradiation with precise thermoregulation of the double jacketed sonoreactor demonstrates the potential of this technique for studying and optimizing all the reaction parameters. The results not only reveal that the optimized ultrasonic conditions lead to excellent epoxidation outcomes with 96% yield and 98% selectivity but also to higher selectivities toward the epoxidation product compared with silent conditions.

Full text of DOI:10.1016/j.ultsonch.2018.12.038

Accepted Manuscript
High frequency ultrasound as a tool for elucidating mechanistic elements of
cis-cyclooctene epoxidation with aqueous hydrogen peroxide
Tony Cousin, Gregory Chatel, Nathalie Kardos, Bruno Andrioletti, Micheline
Draye
PII:
S1350-4177(18)31542-6
DOI:
https://doi.org/10.1016/j.ultsonch.2018.12.038
ULTSON 4435
Reference:
To appear in:
Ultrasonics Sonochemistry
Received Date:
Revised Date:
Accepted Date:
9 October 2018
4 December 2018
27 December 2018
Please cite this article as: T. Cousin, G. Chatel, N. Kardos, B. Andrioletti, M. Draye, High frequency ultrasound as
a tool for elucidating mechanistic elements of cis-cyclooctene epoxidation with aqueous hydrogen peroxide,
Ultrasonics Sonochemistry (2019), doi: https://doi.org/10.1016/j.ultsonch.2018.12.038
This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers
we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and
review of the resulting proof before it is published in its final form. Please note that during the production process
errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

High frequency ultrasound as a tool for elucidating mechanistic elements of
cis-cyclooctene epoxidation with aqueous hydrogen peroxide
a,b
a
a
b
a
Tony Cousin , Gregory Chatel , Nathalie Kardos , Bruno Andrioletti † and Micheline Draye †
a
Univ. Savoie Mont Blanc - LCME, F- 73000, Chambéry, France.
Univ Lyon, Université Claude Bernard Lyon 1, INSA-Lyon, CPE-Lyon, ICBMS-UMR CNRS 5246, Campus Lyon-Tech la Doua, Bât. Lederer, 43
b
Boulevard du 11 Novembre 1918, 69622 Villeurbanne, France.
The use of high frequency ultrasound (800 kHz) highlights the non-radical character of the cis-cyclooctene epoxidation
mediated by H O and H WO . Combination of moderate mixing brought by the ultrasonic irradiation with precise
2 2 2 4
thermoregulation of the double jacketed sonoreactor demonstrates the potential of this technique for studying and
optimizing all the reaction parameters. The results not only reveal that the optimized ultrasonic conditions lead to excellent
epoxidation outcomes with 96% yield and 98% selectivity but also to higher selectivities toward the epoxidation product
compared with silent conditions.
Keywords : Epoxidation; Cis-cyclooctene; Tungsten-based catalyst; Hydrogen peroxide; Ultrasound.
1
. Introduction
Epoxides are important oxygenated intermediates leading to a large variety of daily products
including epoxy resins, surfactants, cross-linked polymers, plasticizers, paints or surface coating agents
1]. However, the synthesis of epoxides usually involves non-environmentally-friendly oxidants such as
iodosylbenzene, chlorate and perchlorate salts, amine and pyridine-N-oxides, peracids and peroxides
1–3]. Despite their high oxidizing potential these species are converted into undesirable by-products
[
[
such as halogenated salts, amines, pyridines, acids or alcohols and that must be treated.
For this reason, the development of clean and efficient processes for the manufacture of epoxides
is a great challenge. Over the past few decades, hydrogen peroxide has witnessed a growing interest
for oxidation reactions thanks to its low environmental impact. Indeed, it is non-toxic and only releases
water as theoretical by-product [4]. In addition, with a production of 4.5 metric tons/year, H O is a
2 2
readily available and cheap oxidant [4–6]. After molecular oxygen, it is thereby more accessible than
other oxidizing compounds and displays high oxygen content [2].
2 2
Epoxidation reactions with H O are also discussed intensively in the literature. More specifically,
the use of transition metal based catalysts under solvent-free conditions have received much attention
to develop eco-friendly epoxidations [2]. Among them, tungsten-based catalysts have been studied
recently thanks to their high oxidizing potential, non-toxicity and low cost [7–9].
Study of their activity is often assessed with the epoxidation of cis-cyclooctene as a model
compound. High affinity of its double-bond towards electrophilic oxidants makes it a substrate of
interest [3,10]. As an illustration, with the W-H
commonly epoxidized 2 to 5 times faster than other olefins with conversions and yields above 90%
3,11,12]. Nevertheless, in spite of the well documented literature dealing with this reaction, higher
2 2
O based oxidizing systems, cis-cyclooctene is
[
reaction kinetics observed with this model compound did not allow any in-detail description on the
reaction parameters on the outcome of the reaction. Besides, no clear explanation on the contribution
•
of HO that is commonly produced from H
2 2
O has been proposed to date to complete the proposed
mechanisms.
Ultrasound-assisted syntheses have received a growing attention over the past few decades thanks
to the multiple effects brought by ultrasonic waves to the media [13]. Indeed, ultrasonic effects are the
consequence of cavitation phenomenon occurring through nucleation, growth and brutal collapse of
micrometric bubbles in elastic media leading to modifications of different nature. When imploding,
these bubbles create local zones where intense temperatures (up to 5,000 K) and very high pressures
(up to 1,000 atm) are reached, leading to both important physical and chemical effects. At low
frequencies, physical effects resulting from violent microjets and shearing forces are preferentially
observed while chemical effects coming from solvent sonolysis and radical formation prevail under
high frequency ultrasound [14,15].

2 2
Recent studies reported the multiple benefits brought by low frequency ultrasound for H O -
mediated epoxidations, including enhanced mass transfer, reduced reaction times and decreased use
of harmful compounds [16–21]. Conversely, very few examples relate the use of high frequency
ultrasound for organic synthesis. Actually, the corresponding reports mainly focused on
alkylpolyglycoside polymerization or oxidation of hexoses to uronic acids [22,23]. To date, no use of
2 2
high frequency ultrasound has been described to carry out H O -mediated epoxidations. In this study,
we demonstrate that a high frequency ultrasonic reactor (800 kHz) cannot only reveal elements of cis-
cyclooctene epoxidation that are not accessible under silent conditions but also enhances its
environmental performances.
H O (35 wt. %)
H WO4
PTC*
2
2
2
O
)))) (800 kHz)
Fig. 1: Cis-cyclooctene epoxidation mediated by hydrogen peroxide and high frequency ultrasound. *PTC = Phase Transfer
Catalyst.
2
. Results and discussion
2 2
Among the literature describing the cis-cyclooctene epoxidation with H O and a tungsten-based
catalyst, the results presented by Reedijk et al. are the most interesting in terms of green chemistry
12]. Indeed, the solvent-free conditions used involve a catalytic system made of 0.2 mol % of Na WO
WO , Aliquat 336® as Phase Transfer Catalyst (PTC) and chloroacetic acid as promoter. After 30 min
at 60 °C in the presence of 1.5 eq. H (50% in water), cyclooctene is epoxidized in 89% yield and 99%
[
2
4
,
H
2
4
2 2
O
selectivity. These excellent results led us to use similar conditions in order to compare the kinetics of
this reaction between silent conditions and ultrasonic irradiation. As illustrated in Fig. 2, even in the
absence of chloroacetic acid, a catalyst loading of 0.2 mol % affords very good results after 30 min of
reaction under silent conditions. Interestingly, over this period, the conversion and the yield increase
-1
very sharply almost reaching their final values after 15 min (TOF = 1350 h over 15 min). As already
observed in the literature, these results illustrate faster kinetics for the cis-cyclooctene epoxidation
than with other substrates under similar conditions [3,11,12]. Interestingly, in the meantime, the
temperature also strongly increases from 25 °C to almost 95 °C within only 10 min due to the
exothermic character of the epoxidation. To assess the potential contribution of the temperature
increase to the fast improvement of the conversion and yield, the reaction was carried out using a
double-jacketed high frequency ultrasound reactor (picture in ESI). An acoustic power of 0.66 W.mL-1
was applied in order to ensure a steady 60 °C temperature during sonication. Under ultrasonic
conditions, both conversion and yield increase slower than under silent conditions (Fig. 2). Indeed,
while the reaction is almost completed after 30 min reaction under magnetic stirring, 90 min are
needed to reach final conversion and maximum yields under ultrasound. Such slower kinetics can be
attributed to the precise control of the temperature imposed by the water-cooled reactor as the
reaction mixture did not exceed 60 °C during sonication. These preliminary results reveal that a
thermo-regulated reactor and the use of high frequency ultrasound lead to a slower increase of
-1
conversion and yield against time (TOF = 380 h over 15 min). The moderate conditions reached thanks
to the ultrasonic reactor allowed us to study the influence of each reaction parameter and to optimize
them independently.

1
00%
9
8
7
6
5
4
3
2
1
0%
0%
0%
0%
0%
0%
0%
0%
0%
Conversion (Δ)
Yield (Δ)
Conversion ( )))) )
Yield ( )))) )
0
%
0
50
100
Time (min)
Fig. 2: Evolution of cis-cyclooctene epoxidation results under silent and ultrasonic conditions versus time.
Cis-cyclooctene (280 mmol), H (35 wt. %, 1.5eq.), H WO (0.2 mol %), Aliquat 336® (0.2 mol %), 25-60°C. Silent conditions (Δ):
2
O
2
2
4
-1
1
,000 rpm. Ultrasonic conditions ( )))) ): f = 800 kHz, Pacous = 0.66 W.mL . Conversion (transformed starting material) and epoxide
yield (on the basis on starting cis-cyclooctene) calculated by internal quantification during GC analysis.
The most critical reaction parameters for cis-cyclooctene epoxidation were determined using high
frequency ultrasound. As total electric consumption becomes higher under ultrasound than under
silent conditions after 1 h, optimization was made over 1 h studies (See example of energy
consumptions under optimized conditions in Fig. S2 in ESI). Firstly, we investigated the chemical action
of high frequency ultrasound on aqueous hydrogen peroxide. Indeed, as exposed previously, the
subsequent formation, growth and collapse of the cavitation bubbles under high frequency irradiation
leads to the homolytic cleavage of water O-H bonds (Fig. 3, Eq. (1)) [24,25]. This reaction leads to the
•
formation of highly reactive HO radicals that can also be produced through homolytic scission of the
hydrogen peroxide O-O bond (Fig. 3, Eq. (2)). Thus, the reactivity of such species toward the double
bond of cyclooctene can be studied.
))))
(
1) H O
HO + H
2
))))
(
2) H O
2
2
2 HO
•
Fig. 3: HO formation under ultrasonic irradiation of aqueous solution of hydrogen peroxide.
The chemical action of high frequency ultrasound on water homolysis has been determined by
•
measuring the HO production kinetics thanks to a chemical dosimeter based on the Weissler reaction
-
1
[
26]. Under a selected acoustic power of 0.58 W.mL , the open-air ultrasonic irradiation of 50 mL
•
-1 -1
deionized water leads to the production of HO radicals at a rate of 0.784 mmol L h .
As exposed above, hydroxy radicals can also be produced by sonolysis of the H peroxide bond. In
order to assess the amount of hydrogen peroxide decomposed under high frequency ultrasound, we
studied the degradation of H under ultrasonic irradiation over 1 h (Fig. 4). Fig. 4 reveals that
hydrogen peroxide is little decomposed under these conditions. After 1 h of ultrasonic irradiation, less
than 2% loss of hydrogen peroxide is observed. In order to evaluate the effect of the catalyst on H
2 2
O
2 2
O
2 2
O
decomposition under ultrasound, the study was undertaken in the presence of tungstic acid used in a 5
times higher concentration than the one used previously for cis-cyclooctene epoxidation. Interestingly,
even the addition of tungstic acid does not catalyze hydrogen peroxide decomposition under ultrasonic
conditions. This observation can be illustrated by the formation of stable peroxotungstates from the
reaction between H
results indicate that, in the absence of any organic substrate, HO radicals formed from water or
hydrogen peroxide sonolysis do not undergo side reactions leading to progressive H decomposition.
2 4 2 2
WO and H O preventing hydrogen peroxide from decomposition [27,28]. These
•
2 2
O
Thus, the ability of tungstic acid to preserve hydrogen peroxide from degradation under ultrasound
and its very good activity toward cis-cyclooctene epoxidation led us to select this catalyst to start
optimization study.

40
35
30
25
20
15
10
5
0
Time (min)
0
15
30
45
60
H
2
O
2
alone
H2O2 + H2WO4
2 2 2 4
H O + H WO
H2O2 alone
Fig. 4: Evolution of %H
2
O
2
during high frequency sonication of aqueous hydrogen peroxide solution alone or in the presence of
-1
H
2
WO versus time. H
4
2
O
2
(35 wt. %, 50 mL), H
2
WO
4
(6 mmol), f = 800 kHz, Pacous = 0.58 W.mL .
In order to complete the catalytic system used to study cis-cyclooctene epoxidation under biphasic
+
-
3 4
conditions and ultrasound, we selected Oct MeN HSO as PTC. The choice of this onium salt was
driven by the excellent results reported by Noyori et al. for alkene epoxidation, alcohol oxidation and
alkene oxidative cleavage applied for a broad substrate scope [27,29,30]. The optimization study
started by investigating the influence of the amount of H
O
2 2
on the outcomes of the reaction (Fig. 5).
1
00%
8
6
4
2
0%
0%
0%
0%
Conversion
Yield
0
%
Eq. H2O2
0
1
2
3
4
5
Fig. 5: Influence of the H
2 2
O amount on the results of cis-cyclooctene epoxidation under high frequency ultrasound.
+ -
Cis-cyclooctene, H (35 wt. %), H WO (1 mol %), Oct MeN HSO (1 mol %), 25-50°C, 1h. Ultrasonic conditions: f =800 kHz,
2
O
2
2 4 3 4
-
1
P
2 2
acous = 0.58 W.mL . Cyclooctene and H O amounts are determined to reach a 50 mL reaction volume. Conversion (transformed
starting material) and epoxide yield (on the basis on starting cis-cyclooctene) calculated by internal quantification during GC
analysis.
As illustrated in Fig. 5, when the reaction is performed in the only presence of water (0 equivalent
of H O
2 2
), a very small amount of cis-cyclooctene is converted (6%) and no epoxide is observed (0%). It
WO under these conditions. These
observations suggest that the HO radicals formed from the sonolysis of water do not have a significant
impact on the reaction. Study of the reaction in the presence of 0.5 equivalents of H allowed us to
assess the influence of OH radicals originating from hydrogen peroxide sonolysis. Under high
frequency ultrasound, O-O homolytic cleavage of 0.5 equivalent of H leads to the theoretical
is worth noting that also no epoxide is formed without H
2
4
•
2 2
O
•
2
O
2
•
formation of 1 equivalent of HO . However, under these conditions, conversion and yield did not
exceed 50% (44% and 42% respectively), indicating that molecular hydrogen peroxide is the limiting
reactant. The limited effect of the HO radicals on this reaction may be correlated to the cis-
cyclooctene aqueous solubility. Indeed, even if the addition of HO radicals on cis-cyclooctene
2 2
proceeds faster than their recombination into H O (rate constants: 3.1 x 10 against 6.2 x 10 L.mol
s calculated from refs [31,32]), the aqueous solubility of cis-cyclooctene (from 22.9 to 43.5 mg.L in
temperature range of the study, calculated from ref [33]) is too low to react quantitatively with HO in
aqueous phase. In order to confirm that HO radicals do not have influence on epoxidation results, the
•
•
1
0
9
-
1
-1,
-1
.
•
•
reaction has been undertaken in the presence of tert-butanol as radical inhibitor. By carrying out the
epoxidation in the presence of 0.5 equivalent of H O , similar conversion and yield as those observed
2 2
without radical inhibitor have been found (48% and 46% respectively).
•
Consequently, these results show that HO radicals do not contribute to cis-cyclooctene epoxidation:
the reaction occurs through a non-radical mechanism under high frequency ultrasound. In our
conditions, the chemical action of high frequency ultrasound does not affect the epoxidation
mechanism: it can be compared to a physical activation technique. Consequently, this reaction can be

classified as type II reaction, also known under “false sonochemistry” [14,34]. In spite of excellent
results obtained with 2.2 equivalents of H , the use of 120% stoichiometric excess of hydrogen
2 2
O
peroxide is not attractive in terms of Atom Economy. Besides, conversion and yield reached under
these conditions are too high (97% and 88% respectively) to adjust the other reaction parameters to
enhance epoxidation results. Since lower conversion (83%) and yield (79%) obtained in the presence of
1
.5 H
2
O
2
equivalents are high enough to study the influence of reaction parameters, we decided to set
at 1.5 equivalents for the rest of this study.
the amount of H
2 2
O
The nature of the PTC on the results of epoxidation was next studied. To this end, 3 common onium
+
-
salts used in the literature with tungsten-based catalysts were compared (Fig. 6): Oct
3
MeN HSO
4
,
+
-
+
-
Oct MeN Cl (Aliquat 336®), and (C16H32)C H N Cl (CetylPyridinium Chloride = CPC). All of these phase
3
5
5
transfer catalysts have been selected for their activity in a large variety of epoxidation and oxidation
reactions with tungsten-based catalysts [27,30,35–37]. The presence of these compounds in the
catalytic system was justified by studying the reaction without any phase transfer material. As shown
in Fig.6, very low conversion and yield were observed in the absence of PTC. Conversely, the addition
of selected onium salts resulted in moderate to high epoxidation yields. These results highlight the
crucial role of the phase transfer catalyst for the effective catalytic conversion of cis-cyclooctene into
epoxide. Besides, it is noteworthy that even under the moderate mixing reached by high frequency
ultrasonic irradiation, high epoxidation results were obtained when using PTC. Under these conditions,
ultrasound showed that a strong mixing is not necessary to afford very good conversion. Comparison
of the results obtained in the presence of onium salts revealed that best epoxidation yields are reached
+
-
3 4
with Oct MeN HSO and Aliquat 336® with yields above 80%. Indeed, the tricaprylmethylammonium
cation forming these onium salts displayed a higher activity than cetylpyridinium cation present in CPC
that led to moderate 51% yield. The nature of the anion on the pH of the media also greatly influenced
the results of the reaction. On the one hand, while cyclooctene is almost converted quantitatively in
+
-
3 4
the presence of Oct MeN HSO , Aliquat 336® only affords 83% conversion. These results can be
explained by the lower pH brought by the hydrogen sulfate anion (pH < 1) during the reaction leading
to enhanced oxidizing power of hydrogen peroxide. Indeed, equation of Eh-pH diagram of hydrogen
peroxide (Eq. (3)) reveals that H
O
2 2
redox potential increases at lower pH ranges [7]:
2푂2 + 2퐻 + + 2푒 = 2 퐻2푂
‒
퐸 = 1.74 ‒ 0.06푝퐻
(3)
퐻
2 2
Activation of W-based catalyst by H O is thus favored to form active peroxo species as pH
decreases [27,28,36]. On the other hand, very acidic conditions brought by the hydrogen sulfate anion
during the reaction led to the formation of a higher amount of by-products from cis-cyclooctene.
Indeed, epoxide ring opening is favored in such acidic conditions. In contrast, mild acidic conditions (pH
=
3) reached thanks to the buffering action of Aliquat 336® during the reaction resulted in less side
reactions. As it is low cost, commercially available and shows very good epoxidation results, Aliquat
36® has been selected as optimal PTC for the reaction.
3
1
00%
Conversion
Yield
8
6
4
2
0%
0%
0%
0%
0
%
Oct3MeN+
HSO4-
pH < 1
Aliquat 336
CPC
No PTC
pH = 3
pH = 6
pH = 1
Fig. 6: Influence of different Phase Transfer Catalysts (PTC) on the results of cis-cyclooctene epoxidation under high frequency
ultrasound. Cis-cyclooctene (185 mmol), H (35 wt. %, 275 mmol, 1.5 eq.), H WO (1 mol %), PTC (1 mol %), 25-50 °C, 1 h, f =
00 kHz, Pacous = 0.58 W.mL . Conversion (transformed starting material) and epoxide yield (on the basis on starting cis-
cyclooctene) calculated by internal quantification during GC analysis.
O
2 2
2
4
-1
8

Catalytic involvement of Aliquat 336® on epoxidation has been assessed by studying the reaction in the
only presence of H 35% and Aliquat 336® (1.5 eq. and 1% respectively); it led to a conversion below
0% and 0% epoxide after 1h of reaction. In a similar way, 0% epoxide is observed with 1.5 eq. H
only. These results indicate that PTC has no direct interaction with H during the reaction. These
2 2
O
1
2 2
O
2 2
O
observations are consistent with mechanisms proposed in the literature showing that PTC allows
bringing active peroxo-tungsten species from aqueous phase to organic phase to epoxidize cis-
cyclooctene.
Based on results on the investigation of cis-cyclooctene epoxidation under high frequency ultrasound
and proposed mechanisms in the literature, mechanism occurring through a molecular pathway was
suggested (Fig. 7) [27,28,38].
-
H+
O
O
O
a)
2
-
W
2-
2 H+
O
O
O
O
O
O
O
O
O
OH
O
O
H2O2
O
W
W
O
2 H+
=
O
H2WO4
+
-
H+
O
O
OH
W
O
O
W
O
2
O
O
Active
O
O
O
O
Peroxo-tungsten
complex
b)
O
2-
2 Q+
2-
Q+
2
O
O
O
O
O
O
O
O
O
W
W
O
O
2
2
Organic
Phase
2 Q+
- 2 Q+
+ 2 H+
+
-
2 H+
Aqueous
Phase
2- 2 H+
2-
H+
2
O
H
H
H
O
O O
O
O
O
O
H
O
W
O
W
O
O
O
O
2
2
H
H
H
O
O
O
H
Fig. 7: Hypothesis of mechanism of H
2
O
2
mediated cis-cyclooctene epoxidation under high frequency ultrasound a) Formation of
active peroxo-tungsten complex. b) Detailed epoxidation mechanism under phase transfer catalysis conditions (Aliquat 336®:
+
-
-
Oct
3
MeN Cl = Q+ X ) Adapted from [27,28,38]
2 4 2 2
In aqueous phase, the reaction between H WO and H O results in the formation of mononuclear
tungsten peroxo-species that lead to an active dimeric peroxo-tungsten complex (Fig.7a). This complex
2
-
([W
2 3 2 4
O (O ) ] ) is transferred from the aqueous phase to the organic phase by 2 quaternary ammonium
+
+
moieties of Aliquat 336® (Oct MeN = Q in Fig. 7b) where epoxidation of cis-cyclooctene occurs. The
3
efficiency of [Oct
presence of the two asymmetrically bounded  -peroxide ligands in [W
bond weaker and easier to break [38]. The catalyst is then renewed by reacting with another molecule
3 2 2 3 2 4
MeN] [W O (O ) ] for alkene epoxidation has been shown to derive from the
2
2-
2 3
O (O
2 4
) ]
making the W-O

2 2
of H O at the interface between organic and aqueous phase or in aqueous phase after cation
+
+
exchange of Q by H .
Further optimizations on the temperature, the amount of catalysts and the acoustic power led us to
use only 0.75 mol % of H
0
2
WO
.61 W.mL at 80 °C. Finally, optimization of reaction time under ultrasound showed that the best
epoxidation results are obtained in 30 min. Indeed, as illustrated in Fig. 8, when reaction time exceeds
0 min, selectivity decreases from 98 to 94%. Under high frequency ultrasound, the best results are
reached in only 30 min of reaction at 80 °C where cyclooctene oxide is obtained with 96% yield and
8% selectivity.
4
and Aliquat 336® and high frequency ultrasound at an acoustic power of
-1
3
9
1
00%
9
9
8
8
7
5%
0%
5%
0%
5%
Conversion (Δ)
Yield (Δ)
Conversion ( )))) )
Yield ( )))) )
5
15
25
35
45
Time (min)
Fig. 8: Results of cis-cyclooctene epoxidation under high frequency ultrasound and silent conditions versus time.
2 2 2 4
Cis-cyclooctene (185 mmol), H O (35 wt. %, 275 mmol, 1.5 eq.), H WO (0.75 mol %), Aliquat 336® (0.75 mol %), 25-80°C. Silent
-1
conditions (Δ): 1,000 rpm. Ultrasonic conditions ( )))) ): f = 800 kHz, Pacous = 0.61 W.mL . Conversion (transformed starting
material) and epoxide yield (on the basis on starting cis-cyclooctene) calculated by internal quantification during GC analysis.
A comparative study was next carried out under magnetic stirring at 80 °C. Under silent conditions,
conversion and yield reach their final values after 15 min reaction. Interestingly, between 15 and 45
min reaction, the selectivity toward epoxide is always higher under ultrasound than under silent
conditions. Indeed, under silent conditions, the selectivity did not exceed 91% while the reaction
afforded cyclooctene oxide in 94 to 99% selectivity under ultrasonic activation. These observations can
be explained by the faster temperature increase observed under magnetic stirring. Actually, under
silent conditions at 1,000 rpm, the temperature measured in the medium showed a sharp increase
from 25 to 95 °C in 5 min only and remained constant for 10 min (Fig. 9). Strong mixing of biphasic
media under such temperatures would thereby lead to more side reactions. Conversely, precise
thermoregulation and moderate mixing provided by our high frequency ultrasound reactor allowed a
good control of the temperature at 80 °C after 10 min of irradiation, leading to high selectivity toward
epoxidation product. Thus, the high frequency ultrasound reactor is not only an efficient tool to unveil
mechanistic aspects of cis-cyclooctene epoxidation but is also an innovative direct activation
technique. More specifically, the unique combination of mild mixing brought by ultrasonic activation
and precise temperature control allowed enhancing the selectivity of the reaction. Besides, the
sonoreactor enables lowering the overall energy consumption compared to silent conditions
contributing to enhance the green character of the reaction (See energy calculations under Fig. S2 in
ESI).
1
00
8
6
4
2
0
0
0
0
Δ
))))
Time
0
10
20
30
40
50
(min)

Fig. 9: Temperature profiles during cis-cyclooctene epoxidation at 80°C under silent and ultrasonic conditions.
Cis-cyclooctene (185 mmol), H (35 wt. %, 275 mmol, 1.5 eq.), H WO (0.75 mol %), Aliquat 336® (0.75 mol %), 25-80 °C. Silent
conditions (Δ): 1,000 rpm. Ultrasonic conditions ( )))) ): f = 800 kHz, Pacous = 0.61 W.mL .
O
2 2
2
4
-1
3
. Experimental section
3
.1. Reagents, apparatus and analysis
Gas chromatography was performed on a HP 6890 Series gas chromatograph from Hewlett Packard
using a flame-ionization detector and equipped with an Optima-5MS Accent capillary column
(dimethylpolysiloxane, 30 m x 0.25 mm x 0.25 µm) from Marcherey Nagel.
The high frequency ultrasonic cup-horn system is shown in ESI. It is made up of a jacketed Pyrex
reaction cell (internal diameter x height: 60 x 185 mm) equipped with a high frequency transducer
which resonance frequency was measured at 807 ± 1 kHz. Cooling of the piezoelectric transducer was
ensured by a fan to avoid degradation from heating due to Joule effect. A homemade 800 kHz
generator was used to supply energy to the high frequency transducer (in the presence of 50 mL of
-1
-1
deionized water: Pacous = 0.58 W.mL for Pelec = 60 W; Pacous = 0.66 W.mL for Pelec = 73 W). A Minichiller
Huber cooling system (Offenburgh, Germany) was filled with deionized water and used for
thermoregulated experiments. The temperature was measured by a Pt-100 resistance probe (100 Ω at
0
°C; 119 Ω at 50 °C) within about 0.1 °C precision. The total liquid volume reached 50mL for the whole
reactions.
Acoustic power of ultrasonic reactor was determined in deionized water using calorimetry according to
•
procedure described in the literature [39]. Kinetic of formation of HO radicals was evaluated by iodide
dosimetry using UV-Vis spectroscopy [26,40,41].
All chemicals were obtained and used without further purification. Cis-cyclooctene, and potassium
permanganate were purchased from Acros. Tungstic acid and methylytrioctylammonium
hydrogensulfate were obtained from Aldrich. Aliquat 336® and hexadecylpyridinium chloride were
provided by Alfa Aesar. Hydrogen peroxide (aqueous solution, 35 wt. %) and potassium iodide were
purchased from Honeywell. Permanganate titration of hydrogen peroxide solution was performed
2 2
regularly according to literature procedure for accurate determination of H O concentration [42].
3
.2. General procedures
3
.2.1. Cis-cyclooctene epoxidation under silent conditions
In a 250 mL round bottom flask, aqueous solution of hydrogen peroxide (280 mmol, 27.90 g, 1.5 eq., 35
wt. % solution) was added to a mixture of H WO (1.4 mmol, 0.346 g, 0.75 mol %) and Aliquat 336® (1.4
2
4
mmol, 0.56 g, 0.75 mol %). The aqueous solution was stirred at room temperature for 2 min before
adding cis-cyclooctene (185 mmol, 21.44 g). Round bottom flask was equipped with a condenser and
the biphasic mixture was stirred at 80 °C without any incubation period at 1,000 rpm. After 1 h
2 2
reaction, aqueous phase is separated from the organic layer and thoroughly washed with CH Cl (3 x 30
mL) in order to extract remaining cyclooctene and newly formed products. After evaporation of the
solvent under reduced pressure, remaining liquid residue and organic phase were analysed by gas
chromatography for quantification by internal standard method (dodecane used as internal standard).
3
.2.2. Cis-cyclooctene epoxidation under high frequency ultrasound
Reactants were introduced into the high frequency sonochemical reactor according to the same
procedure as previously before closing head of reactor with rubber plug. Double-Jacket of
sonochemical reactor was then filled with water at 25 °C thanks to a Minichiller Huber cooling system
and the mixture was subjected to 800 kHz ultrasonic irradiation (60 mm diameter piezoelectric
-1
ceramic, Pelec = 67 W, Pacous = 0.61 W.mL ) for 1 h. Reactor was degassed at regular intervals to avoid
pressure increase. At the end of reaction, aqueous and organic phases were treated and analysed
following the same procedure as previously.

Note : as sonochemical efficiency of a sonoreactor was demonstrated to depend on liquid height [41],
amounts of reactants were calculated to reach a total volume of 50 mL during optimization study.
3
.2.3. Kinetic studies of cis-cyclooctene epoxidation
Reactants were prepared following the same procedures as previously as well as under ultrasonic as
under silent conditions. During the reaction, stirring or irradiation was stopped for a few seconds to
allow sampling of organic phase at regular intervals. Reaction was monitored analysing samples by gas
chromatography. Final results were confirmed by analysing both phases according to the same
procedure as previously.
4
. Conclusion
2 2
In this work, the use of high frequency ultrasound proved that H O -mediated epoxidation of cis-
cyclooctene with a tungsten-based catalyst involves a non-radical mechanism. Study on the nature of
the PTC not only revealed the crucial role of this compound in the catalytic conversion of cis-
cyclooctene but also that mild mixing brought by ultrasonic irradiation is sufficient to lead to high
yields. The unique combination of high frequency ultrasound with a double-jacket reactor thereby
allowed the independent study and optimization of critical reaction parameters to lead cis-cyclooctene
epoxidation with 96% yield and 98% selectivity in only 30 min. More specifically, accurate temperature
control coupled with moderate mixing brought by ultrasound proved to limit the initial temperature
increase of the reaction leading to higher selectivity toward epoxidation product compared to silent
conditions. These results revealed high frequency ultrasonic reactor as a direct activation technique
that enables study, optimization and enhancement of performances of radical non-sensitive reactions.
Application of this innovative tool for the efficient and environmentally benign epoxidation of other
olefinic substrates is currently under study.
Conflicts of interest
There are no conflicts to declare.
Acknowledgements
Authors are grateful to the Région Auvergne Rhône Alpes for their financial support through an ARC
Environnement doctoral research grant (ARC 2016).
References
[
1] G. Sienel, R. Rieth, K.T. Rowbottom, in: Wiley-VCH Verlag GmbH & Co. KGaA (Ed.), Ullmanns
Encycl. Ind. Chem., Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim, Germany, 2000.
2] J.-E. Bäckvall, ed., Modern Oxidation Methods: Second Edition, Wiley-VCH Verlag GmbH & Co.
KGaA, Weinheim, Germany, 2010.
[
[
[
3] S.A. Hauser, M. Cokoja, F.E. Kühn, Catal Sci Technol 3 (2013) 552–561.
4] C.W. Jones, Applications of Hydrogen Peroxide and Derivatives, Royal Society of Chemistry,
Cambridge, 1999.
[
5] N.M. Wilson, D.T. Bregante, P. Priyadarshini, D.W. Flaherty, in: J. Spivey, Y.-F. Han (Eds.),
Catalysis, Royal Society of Chemistry, Cambridge, 2017, pp. 122–212.
[
[
6] R. Ciriminna, L. Albanese, F. Meneguzzo, M. Pagliaro, ChemSusChem 9 (2016) 3374–3381.
7] M.J.N. Pourbaix, N. de Zoubov, Atlas d’equilibres electrochimiques, Gauthier-Villars, Paris,
1
963.
[
8] P.E. Leffler, G. Kazantzis, in: Handb. Toxicol. Met., Elsevier, 2015, pp. 1297–1306.

[
[
9] National Research Council (U.S.)., Handbook of Toxicology., Saunders, Philadelphia, 1956.
10] W.R. Sanderson, in: J.H. Clark, D. Macquarrie (Eds.), Handb. Green Chem. Technol., Blackwell
Science Ltd, Oxford, UK, 2002, pp. 258–305.
[
[
[
11] W. Yan, G. Zhang, H. Yan, Y. Liu, X. Chen, X. Feng, X. Jin, C. Yang, ACS Sustain. Chem. Eng. 6
(
2018) 4423–4452.
12] P.U. Maheswari, P. deꢀHoog, R. Hage, P. Gamez, J. Reedijk, Adv. Synth. Catal. 347 (2005) 1759–
764.
13] G. Chatel, Sonochemistry: New Opportunities for Green Chemistry, WORLD SCIENTIFIC
EUROPE), 2017.
1
(
[
[
[
[
[
14] J.-L. Luche, Synthetic Organic Sonochemistry, Springer US, Boston, MA, 1998.
15] T.J. Mason, Sonochemistry, Oxford Univ. Press, Oxford, 1999.
16] F. Braghiroli, J. Barboza, A. Serra, Ultrason. Sonochem. 13 (2006) 443–445.
17] M. Wang, V. Rajendran, Ultrason. Sonochem. 14 (2007) 46–54.
18] G. Chatel, C. Goux-Henry, N. Kardos, J. Suptil, B. Andrioletti, M. Draye, Ultrason. Sonochem. 19
(
2012) 390–394.
19] V.P. Chavan, A.V. Patwardhan, P.R. Gogate, Chem. Eng. Process. Process Intensif. 54 (2012) 22–
8.
[
2
[
[
[
20] A.P. Chavan, P.R. Gogate, J. Ind. Eng. Chem. 21 (2015) 842–850.
21] M.S. Bhalerao, V.M. Kulkarni, A.V. Patwardhan, Ultrason. Sonochem. 40 (2018) 912–920.
22] P.N. Amaniampong, J.-L. Clément, D. Gigmes, C. OrtizꢀMellet, J.M. GarcíaꢀFernández, Y. Blériot,
G. Chatel, K. DeꢀOliveiraꢀVigier, F. Jérôme, ChemSusChem (2018).
[
[
23] P.N. Amaniampong, A. Karam, Q.T. Trinh, K. Xu, H. Hirao, F. Jérôme, G. Chatel, Sci. Rep. 7
(2017).
24] K.S. Suslick, Y. Didenko, M.M. Fang, T. Hyeon, K.J. Kolbeck, W.B. McNamara, M.M. Mdleleni, M.
Wong, Philos. Trans. R. Soc. Math. Phys. Eng. Sci. 357 (1999) 335–353.
25] D.M. Kirpalani, K.J. McQuinn, Ultrason. Sonochem. 13 (2006) 1–5.
26] A. Weissler, J. Am. Chem. Soc. 81 (1959) 1077–1081.
27] R. Noyori, M. Aoki, K. Sato, Chem. Commun. (2003) 1977.
28] L. Fan, Y. Hong, J. Cao, C. Hu, RSC Adv. 6 (2016) 56656–56660.
[
[
[
[
[
[
29] K. Sato, M. Aoki, M. Ogawa, T. Hashimoto, R. Noyori, J. Org. Chem. 61 (1996) 8310–8311.
30] K. Sato, M. Aoki, M. Ogawa, T. Hashimoto, D. Panyella, R. Noyori, Bull. Chem. Soc. Jpn. 70
(1997) 905–915.
[
[
31] S.M. Aschmann, J. Arey, R. Atkinson, J. Phys. Chem. A 116 (2012) 9507–9515.
32] G. Chatel,"Ultrasonic parameter estimation" in: Sonochemistry, WORLD SCIENTIFIC (EUROPE),
2
017, pp. 27–39.
33] P. Dohányosová, S. Sarraute, V. Dohnal, V. Majer, M.C. Gomes, Ind. Eng. Chem. Res. 43 (2004)
805–2815.
[
2
[
[
[
[
34] J.L. Luche, C. Einhorn, J. Einhorn, J.V. Sinisterra-Gago, Tetrahedron Lett. 31 (1990) 4125–4128.
35] C. Venturello, E. Alneri, M. Ricci, J. Org. Chem. 48 (1983) 3831–3833.
36] C. Venturello, R. D’Aloisio, J. Org. Chem. 53 (1988) 1553–1557.
37] Y. Ishii, K. Yamawaki, T. Ura, H. Yamada, T. Yoshida, M. Ogawa, J. Org. Chem. 53 (1988) 3587–
3
593.
[
[
[
[
38] A.J. Bailey, W.P. Griffith, B.C. Parkin, J. Chem. Soc. Dalton Trans. (1995) 1833.
39] S. Koda, T. Kimura, T. Kondo, H. Mitome, Ultrason. Sonochem. 10 (2003) 149–156.
40] M.H. Entezari, P. Kruus, Ultrason. Sonochem. 1 (1994) S75–S79.
41] S. de La Rochebrochard, J. Suptil, J.-F. Blais, E. Naffrechoux, Ultrason. Sonochem. 19 (2012)
2
80–285.
[
42] N.V. Klassen, D. Marchington, H.C.E. McGowan, Anal. Chem. 66 (1994) 2921–2925.
Cyclooctene epoxidation by H O /H WO /Aliquat 336 under high frequency ultrasound. > High
2
2
2
4
frequency ultrasound proved the non-radical mechanism involved. > High frequency ultrasound

allows step by step optimization of reaction parameters. > High Frequency ultrasound lead to
enhanced selectivities.