Oxidation of Monoterpenes Catalysed by a Water-Soluble MnIII PEG-Porphyrin in a Biphasic Medium

Article abstract of DOI:10.1002/cctc.201800239

It is well established that the transformation of abundant and cheap natural products, such as terpenoids, can produce other more valuable compounds. Thymoquinone, which has a commercial value significantly higher than that of its precursors, can be obtained by oxidation of carvacrol and thymol. In this work, a new water-soluble Mn^III PEG-porphyrin is reported as catalyst in a water/hexane (1:1) biphasic medium for the oxidation of carvacrol and thymol into thymoquinone. The reactions were performed using tert-butyl hydroperoxide as oxidant in the presence of ammonium acetate as co-catalyst, reaching 94 and 78 % of conversion after 5 h of reaction for thymol and carvacrol, respectively. Experiments with oregano essential oil as substrate revealed selective transformation of thymol and carvacrol into thymoquinone. The main advantage of this biphasic system based on a water-soluble catalyst and on substrates and products soluble in hexane, is the straightforward isolation, recovery and recycling of the catalyst by simple phase separation. Recycling studies of the Mn^III PEG-porphyrin using thymol as substrate showed high conversion values throughout four catalytic cycles.

Full text of DOI:10.1002/cctc.201800239

Accepted Article
Title: Oxidation of monoterpenes catalysed by a water-soluble Mn(III)
PEG-porphyrin in a biphasic medium
Authors: Mario Manuel Quialheiro Simoes, Cláudia Neves, Zhanyao
Hou, Richard Hoogenboom, Maria da Graça Neves, Wim
Dehaen, and Joao P. C. Tomé
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ChemCatChem
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Oxidation of monoterpenes catalysed by a water-soluble Mn(III)
PEG-porphyrin in a biphasic medium
[
a]
[b]
[c]
[d]
[c]
Cláudia M. B. Neves, João P. C. Tomé, Zhanyao Hou, Wim Dehaen, Richard Hoogenboom, M.
[
a]
[a]
Graça P. M. S. Neves,* Mário M. Q. Simões*
Abstract: It is well established that the transformation of abundant
and cheap natural products, such as terpenoids, can produce other
more valuable compounds. Thymoquinone, which has a commercial
value significantly higher than that of its precursors, can be obtained
by oxidation of carvacrol and thymol. In this work, a new water-
in high amounts through the oxidation of carvacrol and thymol
(Scheme 1), which are abundantly available in oregano essential
oils. Carvacrol and thymol have been identified as the active
molecules responsible for the antibacterial, antifungal and
[8–11]
antioxidant properties of oregano essential oils,
which make
soluble Mn(III) PEG-porphyrin is reported as catalyst in
a
them very attractive for pharmaceutical and food
[
12,13]
water/hexane (1:1) biphasic medium for the oxidation of carvacrol
and thymol into thymoquinone. The reactions were performed using
tert-butyl hydroperoxide as oxidant in the presence of ammonium
acetate as co-catalyst, reaching 94% and 78% of conversion after 5
h of reaction for thymol and carvacrol, respectively. Experiments with
oregano essential oil as substrate revealed selective transformation
of thymol and carvacrol into thymoquinone. The main advantage of
this biphasic system based on a water-soluble catalyst and on
substrates and products soluble in hexane, is the straightforward
isolation, recovery and recycling of the catalyst by simple phase
separation. Recycling studies of the Mn(III) PEG-porphyrin using
thymol as substrate showed high conversion values throughout four
catalytic cycles.
applications.
Thus, the search for processes for the
synthesis of TQ starting from cheaper and abundant substrates
is a subject of great interest.
Scheme 1. Structures of the substrates (carvacrol and thymol) and the
product (thymoquinone).
Dockal et al. prepared thymoquinone by homogeneous oxidation
Introduction
of thymol and carvacrol in DMF using Co(II) (salen) catalysts,
[
14]
under oxygen flow at low pressure.
Thymoquinone was also
Thymoquinone (TQ) is
therapeutic effects in numerous diseases, but is only available in
limited amounts from natural sources such as Nigella sativa L.
and Monarda fistulosa L. plants.
a
valuable compound that has
efficiently obtained by oxidation of thymol and carvacrol in
acetonitrile in the presence of homogeneous Mn(III) porphyrins
[
15]
and hydrogen peroxide as oxidant. Similar oxidation reactions
catalysed by an zeolite supported tetracationic Mn(III)
porphyrin complex led to <25% conversion of carvacrol and
18% conversion of thymol after 24 h of reaction, in acetonitrile,
[
1–7]
However, it can be obtained
Y
<
[
16]
[
a]
Cláudia M. B. Neves, M. Graça P. M. S. Neves,* Mário M. Q.
Simões*
with 100% selectivity towards TQ. The leaching of the Mn(III)
porphyrin complex to the reaction solution in the presence of
Department of Chemistry & QOPNA
University of Aveiro
H
2
O
2
, accompanied by the partial collapse and changes of the
crystalline structure, causing irreversible deactivation, led to a
3810-193 Aveiro, Portugal
[
16]
E-mail: gneves@ua.pt; msimoes@ua.pt
João P. C. Tomé
Centro de Química Estrutural (CQE)
Departmento de Engenharia Química
Instituto Superior Técnico, Universidade de Lisboa
complete loss of activity when it was recycled.
A mixture of
[
[
b]
c]
thymoquinone, thymohydroquinone, and other benzoquinones
was obtained when the oxidation of carvacrol was performed in
the
presence
of
zeolite-encapsulated
metal-N,N’-
1049-001 Lisboa, Portugal
bis(salicylidene)propane-1,3-diamine complexes [M(salpn)-NaY;
M=Cr, Fe, Zn, Ni, Bi] as catalysts and hydrogen peroxide as
Zhanyao Hou, Richard Hoogenboom
Supramolecular Chemistry Group
Center of Macromolecular Chemistry (CMaC)
Department of Organic and Macromolecular Chemistry
Ghent University
[17]
oxidant, in acetonitrile. The oxidation of carvacrol and thymol
in the presence of Keggin-type heteropolyanions and hydrogen
peroxide, in acetonitrile at reflux, was also less selective,
Krijgslaan 281 S4, B-9000 Ghent, Belgium
Wim Dehaen
Department of Chemistry
KU Leuven,
Celestijnenlaan 200f-bus 02404
affording a mixture of benzoquinones as products, in moderate
[
d]
[18]
conversion.
Recently, the oxidation of thymol and carvacrol
) as
oxidant in the presence of Fe(III) phthalocyanine tetrasulfonate
was studied by using potassium peroxymonosulfate (KHSO
5
[
19]
3001 Leuven, Belgium
(
FePcTS) and a mixture of methanol:water (8:1) as solvent.
The selectivity for thymoquinone was lower than 34% for
carvacrol and lower than 21% for thymol. When H or tert-
Supporting information for this article is given via a link at the end of
the document.((Please delete this text if not appropriate))
2
O
2
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ChemCatChem
10.1002/cctc.201800239
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butyl hydroperoxide (TBHP) were used as oxidants, the yield of
TQ was <1 %. Moreover, by recycling the catalyst, FePcTS, the
authors observed that both thymol and carvacrol conversions
dispersity value below 1.15. Additionally, the successfully
loading of manganese in the core of porphyrin was also
confirmed by the MALDI-TOF MS spectra (Figures S3 and S4)
revealing the expected increase in molar mass after the Mn(III)
coordination.
[
19]
dropped to <5% in the second cycle.
Milos compared the
catalytic efficiency of the Fe(III) complexes of meso-
tetraphenylporphyrin and of phthalocyanine in the oxidation of
In the oxidation reactions, the solvent used was a water/hexane
(1:1) mixture and the substrates selected were carvacrol and
thymol, due to their high solubility in hexane and low solubility in
water. In this way, it was possible to develop a biphasic system
in which the catalyst is water-soluble and the substrate is soluble
in the organic solvent. The product obtained is also poorly
soluble in water, thereby allowing an easy separation of the
catalyst from the substrate and/or product by a simple phase
separation. Other solvent mixtures, such as water/acetone and
water/ethyl acetate were also tested, but in these cases no
oxidation of the substrates was observed.
an oregano essential oil using KHSO
5
or H
acetonitrile. The essential oil was rich in thymol and carvacrol
47.6% and 25.1%), p-cymene (21.4%), -terpinene (2.0%)
among other constituents (<1%). Both catalysts were efficient
using KHSO with a complete or almost complete conversion of
2 2
O as oxidant, in
[20]
(
5
carvacrol and thymol within 1 h (19.1–63.3% yields for TQ), and
the co-catalyst, ammonium acetate, did not influence the
catalytic process. When H O was used as oxidant, a relatively
2 2
slower conversion and lower yields for TQ were observed and
the presence of ammonium acetate affected the oxidation profile
with both catalysts, while p-cymene and -terpinene remained
[
20]
unchanged.
Catalytic studies with Mn(TPP)acac under homogeneous
conditions
Results and Discussion
Before investigating the proposed biphasic catalysis, the best
reaction conditions, namely the substrate/catalyst molar ratio
and the oxidant to be used, were optimized under homogeneous
conditions with Mn(TPP)acac as catalyst, using carvacrol as
substrate, ammonium acetate as co-catalyst and acetonitrile as
solvent at ambient temperature. The oxidant was initially added
in portions with intervals of 15 min, each addition corresponding
to 0.5 equiv relatively to the molar amount of the substrate.
In the present study, taking advantage of the high water-
solubility of porphyrins functionalized with polyethylene glycol
[
21]
(
PEG) chains,
2 4
the Mn(III) complex of H TPP(PEG) was
prepared to be tested as catalyst for oxidation reactions in a
biphasic medium (Scheme 2). The obtained manganese
complex MnTPP(PEG)
4
OAc was characterized by UV-Vis
(
Figure S1), size exclusion chromatography (SEC; Figure S2)
and MALDI-TOF MS (Figures S3 and S4).
2 2
When H O was used as oxidant no oxidation reaction occurred,
even for a substrate/catalyst molar ratio of 25. Additionally, a
change in the catalyst colour from green to red/brown was
observed
after
some
time
indicating
a
possible
destruction/deactivation of the catalyst with H
2
2
O , which was
confirmed by UV-Vis spectrophotometry as the Soret band
disappeared (Fig. 1).
4
Scheme 2. The synthetic strategy to obtain the MnTPP(PEG) OAc from the
H TPP(PEG) .
2 4
Figure S1 compares the UV-Vis spectra of the free-base
porphyrin H TPP(PEG) with the corresponding manganese
complex, MnTPP(PEG) OAc. The manganese complexation of
2
4
4
the free-base porphyrin resulted in a pronounced change in the
Q bands region, with the disappearance of two of the Q bands.
In addition, a bathochromic shift (to higher wavelengths) of the
Soret band and the presence of the metal transition bands at
Figure 1. UV-Vis monitoring of the Mn(TPP)acac catalyst stability in the
homogeneous oxidation of carvacrol in acetonitrile using H
substrate/catalyst molar ratio of 25.
2 2
O as oxidant for a
350-450 nm were observed. SEC revealed that the
MnTPP(PEG) OAc has a narrow molar mass distribution with a
4
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A
totally different result was obtained with tert-butyl
hydroperoxide (TBHP) as oxidant revealing total conversion of
the substrate after 45 min and high stability of the catalyst as
indicated by UV-Vis spectrophotometry (Fig. 2).
It is well known from the literature that, in general, the use of
aqueous H
catalysts in oxidation reactions, since a cooperative action of
water and H can cause catalyst destruction and / or metal
2 2
O can be disadvantageous for the integrity of the
2
O
2
leaching, which is usually in contrast to what happens with
anhydrous TBHP (a solution in decane was used in the present
work) as oxidant. The fact that TBHP is a bulkier molecule than
hydrogen peroxide and the steric effects related with this, are
also mentioned as features that make TBHP less reactive
towards catalyst structure decomposition. The so-called first
generation metalloporphyrin catalysts are particularly prone to
oxidative degradation in the presence of aqueous hydrogen
[
22–26]
peroxide, which is the case of the Mn(TPP)acac.
Figure 3. Carvacrol conversion using Mn(TPP)acac or MnTPP(PEG)
4
OAc as
catalyst, TBHP as oxidant (0.5 equiv every 15 min) and acetonitrile as solvent.
Catalytic studies with MnTPP(PEG)
medium
4
OAc in a biphasic
4
In a next step, the performance of MnTPP(PEG) OAc was
evaluated using a water/hexane (1:1) biphasic medium, under
vigorous stirring. In this case, and using TBHP with additions of
0.5 equiv every 15 min, the reaction was slower and after 120
min (4 equiv of oxidant added) the conversion of carvacrol was
around 70%. The slower reaction was anticipated as the
reaction will mainly occur at the interphase between the
aqueous and organic phases. The reaction mixture was already
in the presence of a large excess of oxidant, since even without
adding TBHP, carvacrol continued to be oxidised to
thymoquinone. In this case, further additions of oxidant would
only lead to destruction of the catalyst. Therefore, the oxidant
was added at once (4 equiv of TBHP) and a conversion of 78%
was obtained after 300 min (Fig. 4). The same conditions were
used in the oxidation of thymol reaching 94% of conversion after
Figure 2. UV-Vis monitoring of the Mn(TPP)acac catalyst stability in the
homogeneous oxidation of carvacrol in acetonitrile using TBHP as oxidant for
a substrate/catalyst molar ratio of 25.
300 min (Fig. 4), with thymoquinone being the only product
detected. Blank experiments, without adding the catalyst and the
co-catalyst were performed and no oxidation was observed.
These good results for the homogeneous catalysis with TBHP
as oxidant led us to test other substrate/catalyst molar ratios
with a smaller amount of catalyst. Almost total conversion of
carvacrol was obtained, after 45 min (Fig. 3), for
a
substrate/catalyst molar ratio of 100 (94%), and the efficiency of
the catalyst was maintained for a substrate/catalyst molar ratio
of 200 (93% conversion, after 45 min). The same result was
obtained using MnTPP(PEG)
4
OAc as catalyst and acetonitrile as
solvent, i.e. under homogeneous conditions (Fig. 3).
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Figure 5. Conversion of carvacrol and thymol in the oxidation of the essential
oil of Origanum vulgare using MnTPP(PEG) OAc as catalyst and TBHP as
4
oxidant in a water/hexane (1:1) biphasic medium.
4
Figure 4. Conversion of carvacrol and thymol using MnTPP(PEG) OAc as
catalyst and TBHP as oxidant (4 equiv added at once) in a biphasic medium of
water/hexane (1:1).
Table 1. Volatile compounds present in the composition of the oregano
essential oil
The same catalytic system was used in the oxidation of an
essential oil of Origanum vulgare. The composition of the
essential oil was determined by GC-MS (Figure S5) revealing
carvacrol (33.2%), thymol (17.0%), and p-cymene (15.3%) as
the main components (Table 1). Other minor components
included terpinen-4-ol (6.6%), trans-caryophyllene (5.6%) and
β-bisabolene (6.3%). The oxidation reaction was monitored by
GC-FID and by GC-MS (Figure S5) to identify the oxidation
Retention time (min)
Compound
%
8
.25
.58
α-Thujene
α-Pinene
1.3
<1.0
1.9
8
1
0.58
1.56
Sabinene
1
β-Myrcene
1.1
[
20]
13.08
3.64
Terpinolene
1.0
products. In line with a previous report by Milos,
it was
1
p-Cymene
15.3
<1.0
<1.0
1.9
observed that the reaction was selective for the oxidation of
thymol and carvacrol. After 3 hours of reaction, thymol and
carvacrol were almost totally converted into thymoquinone (98%
and 89%, respectively – Fig. 5) and the other components
remained practically intact.
Additional assays were performed in order to evaluate if the
separation of thymoquinone was not affected by the recycling of
the catalyst. These experiments were carried with
14.36
14.99
15.66
trans-β-Ocimene
cis-β-Ocimene
-Terpinene
18.53
23.80
27.74
32.09
32.68
39.08
41.29
42.91
44.79
48.88
cis-Sabinene hydrate
Terpinen-4-ol
Carvacrol methyl ether
Thymol
1.1
6.6
2.3
17.0
33.2
5.6
MnTPP(PEG)
4
OAc in water-hexane (1:1) by using thymol as
Carvacrol
substrate and a substrate/catalyst molar ratio of 50.
trans-Caryophyllene
α-Humulene
<1.0
<1.0
6.3
Germacrene D
β-Bisabolene
Caryophyllene oxide
2.7
After each cycle, the catalyst was isolated from the reaction
mixture by simple phase separation, for subsequent reuse. The
evolution of thymol conversion for each catalytic cycle was
monitored by GC-FID and is shown in Fig. 6.
The results show that the efficiency of the catalytic biphasic
system in the first cycle (99% after 120 min) is maintained in the
second catalytic cycle (98% after 150 min). In the third cycle
after 210 min of reaction a high conversion (83%) is still
observed. In the fourth cycle the system was able to convert
50% of thymol after 240 min of reaction. The catalytic activity
decrease of the first generation porphyrin metal complexes
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FULL PAPER
[
22,23]
under oxidative conditions is well known from the literature.
The GC-FID analyses were carried out on a Varian 3900 chromatograph
using helium as the carrier gas (30 cm/s) equipped with a fused silica
capillary DB-5 type column (30 m length, 0.25 mm i.d., 0.25 m film
thickness). The GC-FID chromatographic conditions were as follows:
initial temperature, 100 ºC; temperature rate of 10 ºC/min up to 200 ºC,
followed by a new temperature rate of 40 ºC/min up to 280 ºC which was
maintained for 2 min; injector and detector temperatures were both set at
300 ºC.
Nevertheless, the present biphasic conditions seem to promote
the MnTPP(PEG) OAc stability, allowing its recovery and reuse.
4
In all catalytic cycles the only product obtained was
thymoquinone, which was readily and efficiently separated from
the catalyst by phase separation, thus allowing us to obtain the
thymoquinone in the organic phase, concomitantly to the easy
separation of the catalyst, which remained in the aqueous phase
ready for a new run.
The GC-MS analyses were performed using a gas chromatograph mass
spectrometer (GC-MS Shimadzu QP2010 Ultra) equipped with an AOC-
20i autosampler (Shimadzu, Japan), with the electron impact ionization
(EI) at 70 eV and high-performance quadrupole mass filter. The
separation of compounds was carried out in a DB-5ms column (30 m
length, 0.25 mm i.d., 0.25 m film thickness) using helium as the carrier
gas (40 cm/s). The GC-MS chromatographic conditions were as follows:
initial temperature, 50 ºC which was maintained for 3 min; temperature
rate of 2 ºC/min up to 250 ºC which was maintained for 10 min; injector
temperature, 250 ºC. The mass spectrometer was operated over a range
of m/z 34-450. The ion source was kept at 230 ºC and the interface
temperature at 280 ºC. Chromatographic peaks were identified by
comparing their mass spectra with the equipment mass spectral library
(NIST14s MS Library Database or WILEY229 MS Library Database).
Size exclusion chromatography (SEC) was performed on an Agilent
260-series HPLC system equipped with a 1260 online degasser, a 1260
1
ISO-Pump, a 1260 automatic liquid sampler, a thermostated column
compartment, a 1260 diode array detector (DAD) and a 1260 refractive
index detector (RID). Analyses were performed on a PPS Gram 30
o
column in series with a PPS Gram 1000 column at 50 C. DMA
containing 50 mM of LiCl was used as an eluent at a flow rate of 0.6
mL/min. The SEC traces were analysed using the Agilent Chemstation
software with the GPC add on. Molar mass and PDI values were
calculated against PMMA standards.
Figure 6. Catalyst recycling studies of the MnTPP(PEG)
thymol as substrate, TBHP as oxidant and a substrate/catalyst molar ratio of
0 in a water/hexane (1:1) biphasic medium.
4
OAc catalyst using
5
MALDI-TOF mass spectra were acquired with a Voyager DE-STR
(PerSeptive Biosystem) using a simultaneous delay extraction procedure
Conclusions
(20 kV applied after 233 ns with a potential gradient of 2545 V/mm and a
wire voltage of 200 V) and detection in reflection mode. The instrument
was equipped with a nitrogen laser (emission at 337 nm for 3 ns) and a
flash AD converter (time base 2 ns). The trans-2-[3-(4-t-butylphenyl)-2-
methyl-2-propenylidene]malononitrile (DCTB) was used as matrix.
4
In summary, the water-soluble MnTPP(PEG) OAc is an efficient
catalyst for the preparation of thymoquinone by oxidation of
carvacrol and thymol in a water/hexane (1:1) biphasic medium,
using tert-butyl hydroperoxide as oxidant and ammonium
acetate as co-catalyst. The methodology can be applied directly
to an oregano essential oil particularly rich in carvacrol and
thymol. The catalyst is easily isolated and recovered by simple
phase separation allowing its reutilization.
4
Synthesis of MnTPP(PEG) OAc
MnTPP(PEG)
4
OAc was prepared using the free-base porphyrin
[27]
H
2
TPP(PEG) , which was synthesized as previously described. In a 25
4
mL round bottom flask, equipped with a reflux condenser and a magnetic
stirrer, 50 mg of the free-base porphyrin were dissolved in 5.0 mL of DMF.
The solution was refluxed in the dark, under a nitrogen atmosphere and
then 0.5 mL of pyridine and 10 equivalents of manganese(II) acetate
Experimental Section
3 2 2
[Mn(CH COO) .4H O] were added. The progress of the reaction was
Reagents and Methods
monitored by UV-Vis. The UV-Vis spectrum shows a Soret band shift to a
higher wavelength (λmax=472 nm) and the disappearance of two Q bands
of the free-base macrocycle, thereby confirming the presence of the
complex (Figure S1). The absorption bands of manganese at λmax=380
nm and 402 nm can also be observed. The reaction was complete after 4
h. The heating was switched off and the reaction mixture was kept under
stirring overnight, in the open air and protected from light. The solvent
was evaporated in the rotary evaporator with addition of toluene to
facilitate the solvent removal. The residue was dissolved in
dichloromethane and the organic phase was washed 2-3 times with
water in a separating funnel. The organic phase was passed through a
glass funnel with cotton wool and anhydrous sodium sulphate to remove
Thymol was purchased from Sigma, whereas carvacrol and tert-butyl
hydroperoxide 5.0-6.0 M solution in decane were obtained from Aldrich.
Ammonium acetate was purchased from Scharlau and chlorobenzene
was obtained from Carlo Erba and used as internal standard for the
determination of substrates’ conversion by GC. The synthetic procedure
[
27]
of free base porphyrin was described in our previous work.
Mn(TPP)acac was prepared by the acetylacetonate method as described
[
28]
in the literature.
Cardoso.
The oregano oil was gently provided by Dr. Susana
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ChemCatChem
10.1002/cctc.201800239
FULL PAPER
traces of water. The manganese complexes were crystallized in hexane,
after dissolution in a minimal amount of dichloromethane. The crystals
were filtered under vacuum, using a Hirsch funnel with filter paper, and
washed several times with hexane. The yield, based on the porphyrin,
Thanks are due to National Foundation for Science and
Technology / Ministério da Educação e Ciência − FCT/MEC
(
POPH/FSE) for the financial support to QOPNA (FCT
UID/QUI/00062/2013) and CQE (FCT UID/QUI/0100/2013)
research units. The authors are also grateful to FCT (Portugal)
and POPH/FSE for the PhD Grant to C. Neves
3
was over 90%. UV-Vis (CH CN) λmax, nm (%): 380 (51), 402 (52), 472
(100), 581 (11), 620 (14).
(
(
PD/BD/52531/2014). Z. Hou thanks China Scholarship Council
NO. 201407650003) and Ghent University (BOF 01SC0415) for
General procedure for the oxidation reactions
For the oxidation reactions under homogeneous conditions: a standard
solution of the catalyst was previously prepared in acetonitrile and
reserved in the fridge protected from light until next use. The volume of
the catalyst solution was added to the reactor in accordance to the
corresponding substrate/catalyst molar ratio (S/C). The co-catalyst (0.2
PhD scholarship. RH is grateful to BELSPO(IAP VII/5 Functional
Supramolecular Systems FS2), FWO and UGent (BOF) for
financial support. RH and WD thank FWO for support of the
WOG on Supramolecular chemistry and materials - W0.031.14N.
-
5
mmol ≈15 mg of ammonium acetate), the substrate (7.5 × 10 mol), the
-
5
Keywords: manganese • porphyrin • monoterpenes • oxidation •
internal standard (7.5 × 10 mol of chlorobenzene) and acetonitrile were
added until a final volume of 2 mL. The oxidant was added in aliquots of
biphasic catalysis
0.5 equiv relatively to the molar amount of the substrate every 15 min.
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10
mol; 3.19 mg for a S/C of 200) was dissolved in 1 mL of Milli-Q water,
[
[
3]
4]
and the co-catalyst (0.2 mmol ≈15 mg of ammonium acetate) was added.
-
5
-5
The substrate (7.5 × 10 mol) and the internal standard (7.5 × 10 mol of
chlorobenzene) were dissolved in 1 mL of hexane and added to the
aqueous mixture. The oxidant used was tert-butyl hydroperoxide 5.0-6.0
M solution in decane and 4 equiv relatively to the molar amount of
[5]
[
[
[
[
6]
7]
8]
9]
-
4
substrate (3 × 10 mol) were added at the beginning of the reaction.
Blank experiments were performed under the same conditions without
the catalyst and the co-catalyst.
-
5
For the recycling studies, thymol (7.5 × 10 mol; 11.3 mg) was chosen as
-
6
[10]
substrate and 1.5 × 10 mol of MnTPP(PEG)
4
OAc (12.7 mg for a S/C of
[
11]
50) were used under biphasic conditions. The reaction was stopped
when the substrate was totally converted or when no significant
conversion of the substrate was observed after two successive GC-FID
analyses. At the end of the reaction, the organic phase containing the
internal standard, the tert-butyl hydroperoxide, the thymoquinone and the
unreacted thymol was separated from the aqueous phase containing the
manganese porphyrin and the co-catalyst. The aqueous phase was
washed several times with hexane and controlled by GC-FID to assure
that the aqueous phase was deprived of any thymol, thymoquinone or
internal standard. The aqueous phase was stored in the freezer
protected from light until the next reuse. At each recycling assay, 4 equiv
of oxidant were added. No further co-catalyst was added in the recycles.
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146, 2306–2312.
of ammonium acetate) were dissolved in 1 mL of Milli-Q water. Next, 20
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-
5

L of the oregano oil and 7.5 × 10 mol of the internal standard were
[21]
[22]
[23]
dissolved in 1 mL of hexane and added to the aqueous mixture. Finally, 3
-
4
D. Mansuy, C. R. Chim. 2007, 10, 392–413.
×
10 mol of tert-butyl hydroperoxide 5.0-6.0 M solution in decane were
[
[
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added to start the reaction.
All the reactions were kept under vigorous stirring at 30 ± 1 °C and
protected from light. The conversion of the substrate was monitored by
GC-FID and the stability of the catalyst was checked by UV-Vis
spectrophotometry.
[27]
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[
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Acknowledgements
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ChemCatChem
10.1002/cctc.201800239
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It is well established that the
Cláudia M. B. Neves, João P. C. Tomé,
Zhanyao Hou, Wim Dehaen, Richard
Hoogenboom, M. Graça P. M. S.
Neves,* Mário M. Q. Simões*
transformation of abundant and cheap
natural products, such as terpenoids,
can produce other more valuable
compounds. Thymoquinone, which
has a commercial value significantly
higher than that of its precursors, can
be obtained by oxidation of carvacrol
and thymol. A new water-soluble
Mn(III) PEG-porphyrin is reported as
catalyst in a biphasic medium for the
oxidation of carvacrol and thymol into
thymoquinone.
Page No. – Page No.
Oxidation of monoterpenes catalysed
by a water-soluble Mn(III) PEG-
porphyrin in a biphasic medium
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