Sustainable catalytic epoxidation of biorenewable terpene feedstocks using H2O2as an oxidant in flow microreactors

Article abstract of DOI:10.1039/d1gc01734a

Solvent-free continuous flow epoxidation of the alkene bonds of a range of biorenewable terpene substrates have been carried out using a recyclable tungsten-based polyoxometalate phase transfer catalyst and aqueous H2O2 as a benign oxidant. These sustainable flow epoxidation reactions are carried out in commercial microreactors containing static mixing channels that enable common monoterpenes (e.g. untreated crude sulfate turpentine, limonene, etc.) to be safely epoxidized in short reaction times and in good yields. These flow procedures are applicable for the flow epoxidation of trisubstituted and disubstituted alkenes for the safe production of multigram quantities of a wide range of epoxides. This journal is

Full text of DOI:10.1039/d1gc01734a

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Sustainable catalytic epoxidation of biorenewable
terpene feedstocks using H2O2 as an oxidant in
flow microreactors†
Cite this: Green Chem., 2021, 23,
5449
Received 16th May 2021,
Accepted 6th July 2021
Joshua D. Tibbetts, a,b William B. Cunningham,a,b Massimiliano Vezzoli,c
a
Pawel Plucinskic and Steven D. Bull
*
DOI: 10.1039/d1gc01734a
rsc.li/greenchem
Solvent-free continuous flow epoxidation of the alkene bonds of a chemical products (e.g. flavours, fragrances and vitamins).5
range of biorenewable terpene substrates have been carried out Consequently, the development of new efficient catalytic proto-
using a recyclable tungsten-based polyoxometalate phase transfer cols to transform abundant monoterpene feedstocks into syn-
catalyst and aqueous H2O2 as a benign oxidant. These sustainable thetically versatile intermediates is important, since they
flow epoxidation reactions are carried out in commercial micro- would broaden the range of biorenewable products available
reactors containing static mixing channels that enable common from terpene biorefineries, thus helping improve their econ-
monoterpenes (e.g. untreated crude sulfate turpentine, limonene, omic viability.6,7
etc.) to be safely epoxidized in short reaction times and in good
Epoxides are one of the most synthetically useful functional
yields. These flow procedures are applicable for the flow epoxi- groups,8,9 so the availability of sustainable catalytic protocols
dation of trisubstituted and disubstituted alkenes for the safe pro- that can be used to epoxidize the alkene bonds of monoter-
duction of multigram quantities of a wide range of epoxides.
pene feedstocks to produce monoterpenoid epoxides is highly
desirable.10 Current examples of potentially useful terpene
epoxides include α-pinene oxide which is used as an inter-
mediate to produce commercially valuable fragrance com-
pounds,11 and limonene 1,2-oxide which can be used as a
monomer for the sustainable synthesis of biorenewable poly-
mers.12 We have recently described optimal biphasic solvent-
free protocols that use a preformed tungsten based Venturello
Phase Transfer Catalyst (VPTC) and 30 mol% H2O2 as a benign
terminal oxidant to carry out batch catalytic epoxidation of the
alkene bonds of biorenewable terpene feedstocks (including
untreated CST, see Fig. 1).13 Variations of this batch catalytic
epoxidation process have been used to epoxidize the tri- and/
or di-substituted alkene bonds of a wide range of terpenes,
exhibiting good tolerance of common terpenoid functional
groups (e.g. alcohols and esters). Catalyst recycling studies
revealed that the VPTC could be recycled up to three times for
the sequential production of monoterpene oxides with only
minimal losses in epoxide yield or catalyst activity.13
Treatment of crude epoxides (no work-up) with a hetero-
geneous acid catalyst (Amberlyst-15) was also used to prepare
their corresponding terpene-anti-diols in good yields.13
Introduction
Terpenes and terpenoids are produced in large amounts as
secondary metabolites from plants and microbes, which are
widely used as biorenewable feedstocks for production of
chemicals, flavours, fragrances, drugs and polymers.1–3 Several
unsaturated monoterpenes are currently available in large
volumes as waste by-products from the forestry (e.g. α-/
β-pinene from paper milling) and agricultural (e.g. limonene
from citrus juice production) industries.4 The largest biore-
newable monoterpene source is turpentine, with an estimated
230 000 tonnes of Crude Sulfate Turpentine (CST) produced
annually as a co-product from the Kraft paper pulping process.
Another 100 000 tonnes of gum turpentine are produced
through distillation of resin harvested from tapping trees in
forestry plantations. CST (major components: α-/β-pinene and
3-carene; exact composition dependent on geographic origin)
is currently available at low-cost (∼$220 per tonne), which is
used for production of a range of value-added biorenewable
The scope and versatility of the VPTC/H2O2 catalytic system
means that it has been widely used for batch epoxidation of
the alkene bonds of a wide range of substrates.14–16 However,
we (and others17,18) have described that scale up of batch
biphasic VPTC/H2O2 epoxidation reactions is challenging,
requiring slow dropwise addition of the H2O2 oxidant and
aDepartment of Chemistry, University of Bath, Bath, UK. E-mail: s.d.bull@bath.ac.uk
bCentre for Sustainable Chemical Technologies, University of Bath, UK
cDepartment of Chemical Engineering, University of Bath, Bath, UK
†Electronic supplementary information (ESI) available. See DOI: 10.1039/
d1gc01734a
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since it would enable this catalytic system to be used safely for
large scale epoxide manufacturing. Consequently, we now
describe that preformed VPTC/H2O2 systems can be used for
the flow epoxidation of biorenewable terpene feedstocks in in-
expensive continuous flow microreactors containing static
mixing units, with these simple flow protocols also applicable
for epoxidation of other types of alkene substrate.29
Results and discussion
Previous studies using the VPTC/H2O2 system for batch epoxi-
dation reactions had established that the overall rate of epoxi-
dation was highly dependent on the rate of stirring of these
biphasic reactions.13 Consequently, it was decided to use a
commercial flow microreactor containing static mixing chan-
nels to carry out flow epoxidation reactions, since this would
ensure efficient mass and heat transfer between organic and
aqueous streams, as well as allowing for efficient control of
reaction temperature. The microreactor system used contains
separate channels (2.2 × 2.2 mm) that allow discrete preheat-
ing of organic (terpene and catalyst, solvent free) and aqueous
(aq. 30 wt% H2O2) input streams. Both these organic and
aqueous streams are then flowed into a single static mixer
channel that results in efficient mass transfer between the two
phases (under a positive pressure of up to 7 bar) (see Fig. SI1
and SI2† for details of flow reactor design). Use of this flow
reactor design results in fast solvent-free catalytic epoxidation
reactions under good thermal control to produce an epoxide
and water as the only by-product. Sampling ports were used for
reaction monitoring, with reaction data (e.g. alkene conversion
rates, product ratios, etc.) acquired at different time points
Fig. 1 (a) A recyclable tungsten-based polyoxometalate catalyst using
H2O2 as a stoichiometric oxidant for the solvent free batch epoxidation
of the alkene bonds of monoterpenes present in untreated CST. (b)
Structure of Venturello Phase Transfer Catalyst (VPTC) used in H2O2
based epoxidation reactions.
careful control of reaction temperature to prevent dangerous
delayed onset thermal runaways from occurring.19 The poten-
tial benefits of carrying out catalytic epoxidation reactions
using H2O2 as an oxidant in flow reactors are well established
(for literature examples, see Table 1, entries 1–7), including:
excellent mass and heat transfer; reduced reaction times;
more efficient temperature control; improved safety profiles;
and the ability to telescope reactions to generate epoxide
derivatives.20–28 Therefore, the ability to carry out continuous
VPTC/H2O2 mediated epoxidations of monoterpenes (and
other types of alkenes) in flow reactor systems is desirable, used to modify reaction conditions (e.g. catalyst loadings, flow
Table 1 Conditions used for the catalytic H2O2-mediated epoxidation of alkene substrates (≥6 carbon atoms) that are liquid at room temperature
Entry Substrate
Reactor type
Conditions
Yield
92%
Ref.
22
1
2
3
4
5
Styrene
Corning advanced flow G1
reactor
15% 2,2,2-trifluoroactephenone, 3
equiv. H2O2, MeCN/t-BuOH, 80 °C,
3 min
Cocoa butter (cis-alkenes of
palmitic, stearic and oleic
acid side chains)
Soybean Oil (cis-alkenes of
α-linoleic, linoleic and oleic
acid side chains)
Soapstock fatty acids (cis-
alkenes of linoleic, oleic and (0.8 mm i.d. × 1000 mm)
linolenic acid side chains)
Vapourtec PTFE tubular reactor 2.5% tungsten powder, 1.5%
(1 mm i.d. × 12.7 m length)
77%
23
24
25
26
surfactant, 4% H3PO4, 8 equiv.
H2O2, 80 °C, 80 min
3% H2SO4, 3% EDTA-2Na, 8 equiv.
Microflow slit plate mixer
7.3
H2O2, 8 equiv. HCOOH, 75 °C, 7 min (epoxy number)
Microchannel bioreactor
0.3 wt% Candida rugosa lipase, 1.6
equiv. H2O2, 36 °C, 51 min
85%
98%
96%
Cyclohexene
Glass capillary microreactor
(3 mm i.d. × 36 mm length)
packed with enzyme catalyst
Micro-flow capillary tube
100 mg Novozym® 435, 2 equiv.
H2O2, 2.6 min
6
7
Cyclohexene
Cyclohexene
3% DCC, 8 equiv. Urea H2O2, 80 °C,
12 min
Ti/Nb-SiO2, 3 kPa H2O2 and 3 kPa
27
28
Vapour phase flow reactor
50% selectivity
(fluorinated ethylene propylene cyclohexene, 120 °C, 200 min
tubing)
(+∼50% diol)
8
Cyclohexene
LTF microreactor (7.5 mL)
2% PW4O24[PTC]3, 1.6 equiv. H2O2,
50 °C, 17 min
91%
This work
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rates, etc.) to enable flow epoxidation conditions of individual
alkene substrates to be optimised.
Previous batch epoxidation conditions developed for mono-
epoxidation of the trisubstituted alkene of limonene that
produce good yields of limonene 1,2-oxides in ∼1 h were
chosen as a starting point to commence the flow epoxidation
studies.13 Therefore, an organic flow stream containing
1 mol% PW4O24[PTC]3 catalyst dissolved in limonene and an
aqueous stream containing 30 wt% H2O2 (pH 7.0) was trialled.
The organic and aqueous streams were preheated to 50 °C,
with both streams then flowed into the static mixing channel
(7.5 mL total volume, 50 °C) of the reactor where epoxidation
occurs. Limonene consumption levels at a relatively low flow
rate of 9 mL h−1 proved to be sluggish, requiring >30 min to
reach completion. Conversely, a higher flow rate of 54 mL h−1
resulted in a faster epoxidation rate, however the total volume
of the static reactor gave insufficient residence time to allow
for full limonene consumption. Therefore, a flow rate of 27 mL
h−1 was chosen, which resulted in total consumption of limo-
nene in ∼17 min, with this median flow rate subsequently
used to carry out all further flow optimisation studies (see
Fig. SI3† for flow rate studies). Incremental increases in the
temperature of the flow epoxidation reaction from 25 to 50 °C
resulted in a corresponding increase in the rate of limonene
Fig. 2 Optimal conditions used for the continuous flow epoxidation of
limonene using 1 mol% PW4O24[PTC]3 catalyst and 30 wt% H2O2 (pH
7.0) as oxidant.
epoxidation, with temperatures up to 50 °C resulting in >90% conversions (Fig. 3). 2 mol% VPTC was used to epoxidize the
selectivity for formation of limonene 1,2-oxides alkene bond of 3-carene to give 3-carene oxide 4 in 97% con-
(55 : 45 mixture of diastereomeric epoxides 1a and 1b). Raising version and 98% selectivity in <20 min. Previous batch epoxi-
the temperature above 50 °C led to a decrease in selectivity for dation studies had shown that α-pinene oxide 5 produced
production of limonene 1,2-oxides 1a/1b (<75% at 60 °C), with under VPTC/H2O2 conditions underwent rapid hydrolysis to its
losses in epoxide yield caused by competing epoxidation/ corresponding anti-diol. However, this unwanted epoxide ring-
hydrolysis reactions producing anti-diols 2 and diastereomeric opening rection could be suppressed by inclusion of 30 mol%
bis-epoxides 3 as unwanted side-products. Increasing the Na2SO4 as an additive, which increases the ionic strength of
temperature of the static mixer further to 70 °C resulted in the aqueous H2O2 phase to minimise hydrolysis of the
thermal decomposition of hydrogen peroxide (oxygen bubbles epoxide.13,31 Attempts to carry out additive-free flow epoxi-
observed in reactor channels) that resulted in lower limonene dation of α-pinene also produced α-pinene anti-diols as major
consumption rates (see Fig. SI4† for flow temperature studies). products (<20% α-pinene oxide 5). However, incorporation of
Use of 1 mol% VPT catalyst proved optimal for carrying out the 30 mol% Na2SO4 in the aqueous H2O2 (pH 7.0) flow stream
flow epoxidation of limonene, with higher catalyst loadings and use of a higher 3 mol% VPTC loading resulted in excellent
leading to faster limonene consumption, however lower yields 95% conversion and 95% selectivity for formation of α-pinene
of limonene 1,2-oxides 1a/1b were obtained due to greater oxide 5 (see Fig. SI8 and SI9†). Selective flow mono-epoxidation
amounts of unwanted diols 2 and bis-epoxides 3 being formed of the trisubstituted alkene bond of myrcene could also be
as by-products (see Fig. SI5 and SI6† for catalyst loading achieved, producing myrcene mono-epoxide 6 in 92% conver-
studies).30 Increasing the amount of commercial 30 wt% H2O2 sion and 97% selectivity, with its diene fragment left intact for
(pH 7.0) oxidant from 1.0 to 1.6 equiv. had a positive effect on further functionalisation.
limonene conversion rates, with only a 2% decrease in selecti-
Bis-epoxidation of both trisubstituted alkenes bonds of
vity for 1a/1b observed at higher H2O2 levels (see Fig. SI7† for γ-terpinene was achieved by increasing the amount of 30 wt%
H2O2 concentration studies). These screening studies led to H2O2 used as oxidant from 1.6 to 3.2 equiv., with γ-terpinene-
optimal conditions for flow epoxidation of limonene being bis-epoxide 7 produced in >99% conversion and 60% selecti-
established as 1 mol% VPTC and 1.6 equiv. H2O2 (pH 7.0) at vity. The other products formed were γ-terpinene-monoepox-
50 °C using a 27 mL h−1 total flow rate that produced a resi- ides that could be easily separated by distillation/chromato-
dence time of 16.7 min in a 7.5 mL volume microreactor. graphy and resubjected to the flow epoxidation conditions to
These conditions gave 89% limonene conversion, producing produce more bis-epoxide 7 as required. The diastereo-
limonene 1,2-oxides 1a/1b with >90% selectivity in <20 min selectivity of this bis-epoxidation reaction arises from coordi-
(Fig. 2).
nation of the tungsten catalyst to the oxygen atoms of either
These conditions were then used as a starting point to opti- mono-epoxide, which directs alkene epoxidation to the same
mise flow epoxidation of six other monoterpenes in 92–100% face to exclusively afford the syn-bis-epoxide 7. These flow
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ging, primarily due to the reactive β-pinene oxide undergoing
hydrolysis to its corresponding β-pinene diol. Similar problems
were encountered using our standard flow epoxidation con-
ditions which also produce large quantities of β-pinene diol.
However, use of higher 5 mol% VPTC loadings, 1.6 equiv. of
more concentrated aq. 50 wt% H2O2 (18 M, (pH 7.0)), a higher
temperature of 75 °C and shorter static mixer residency times
of 1.65 min enabled 55% conversion of β-pinene into β-pinene
oxide 10 with excellent 99% selectivity levels (Fig. 3). These
flow conditions proved optimal, with attempts to increase
β-pinene conversion levels by reducing flow rates, increasing
catalyst loadings/temperature, and changing static mixer resi-
dency times leading to lower yields of β-pinene oxide 10.
The synthetic utility of the VPTC/H2O2 catalytic system used
in this flow epoxidation study is well established, and it has
been used to carry out batch epoxidation reactions of a wide
range of alkene substrates.14–18 Consequently, we decided to
carry out a brief exploration of the scope and limitation of the
protocol to flow epoxidize four non-biorenewable substrates
containing challenging disubstituted and monosubstituted
alkene substitution patterns. Flow epoxidation of the cis-di-
substituted alkene bond of cyclohexene (benchmark substrate
used in previous flow epoxidation studies, see Table 1) gave
cyclohexene oxide 11 with excellent 93% conversion and 98%
selectivity. The (E)-alkene bond of trans-ethyl-3-hexenoate
proved less reactive, with flow-epoxidation affording the
desired trans-epoxide 12 in only 26% conversion, but with
100% selectivity levels. Exclusive formation of trans-epoxide 12
means that better yields of this epoxide should be available
using longer flow reaction times in a microreactor with a
larger volume. Flow epoxidation of the gem-disubstituted
alkene functionality of α-methylstyrene required incorporation
of 30 mol% Na2SO4 as an additive to prevent unwanted
epoxide hydrolysis, which produced epoxide 13 in 55% conver-
sion with 89% selectivity. Unfortunately, the alkene bond of
1-octene proved unreactive towards the flow epoxidation con-
ditions, with electron poor monosubstituted alkenes also
found to be unreactive in batch VPTC/H2O2 epoxidation
systems.13
Fig. 3 Catalytic flow epoxidation reactions used for the synthesis of a
range of trisubstituted and disubstituted epoxides 1a/b and 4–13.
Standard flow epoxidation conditions (30 wt% H2O2 (pH 7.0), 50 °C.
Residence Times (R.T.) were 16.7 min unless otherwise stated. FR1 and
FR2 = Flow Rates 1 and 2. See ESI† for individual FR and R.T. values.
Conversion values refer to levels of alkene consumption. Selectivity
values refer to amount of epoxide product relative to substrate con-
sumption levels.
The flow epoxidation protocol was then applied to
untreated industrial CST obtained from a Swedish paper mill,
which is the largest biorenewable monoterpene feedstock
available for use in a terpene biorefinery. Pleasingly, use of
5 mol% catalyst, 2.2 equiv. of 30 wt% H2O2 (pH 7.0), 30 mol%
Na2SO4, 60 °C, 15 min residence time resulted in 95% con-
epoxidation reaction conditions were also used to epoxidize sumption of its three major components [α-pinene (40%),
both trisubstituted alkene bonds of acyclic farnesene (leaving 3-carene (39%), β-pinene (10%), other monoterpenes (11%)].
the less reactive diene fragment intact), with farnesene bis- This resulted in an excellent selectivity profile for production
epoxide 8 generated in 99% conversion and 72% selectivity of 3-carene oxide 4 (99%) and α-pinene oxide 5 (63%), whilst
(along with ∼25% mono-epoxides).
its β-pinene fraction was converted into β-pinene diol (Fig. 4
The less electron rich gem-disubstituted alkene bond of and Fig. SI10†). The major epoxide products could be separ-
(−)-isopulegol was flow epoxidized using 1.6 equiv. H2O2 to ated by fractional distillation of the crude product under
afford isopulegol epoxides 9a/b as a 60 : 40 mixture of diaster- reduced pressure to afford 3-carene oxide 4 (bp 87 °C at
eomers in 92% conversion and 97% selectivity. Previous batch 50 mm Hg) and α-pinene oxide 5 (bp 102 °C at 50 mm Hg),
epoxidation reactions of the exocyclic alkene bond of β-pinene with small amounts of pinane diols recoverable from the distil-
using the VPTC/H2O2 epoxidation protocol had proven challen- lation residue. Pleasingly these flow oxidative conditions also
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dation reaction could be reused to produce a second batch of
1
limonene 1,2-oxide in 83% conversion. H NMR spectroscopic
analysis of the recovered catalyst revealed some degradation
had occurred, however the VPTC was still present as the major
component (see Fig. SI11 and SI12† for details).32 Flow reac-
tions in microreactors can be scaled up using a numbering up
principle, with multiple flow reactions run in parallel to gene-
rate large amounts of product. Based on results obtained for
the flow epoxidation of limonene, it can be calculated that
simultaneous use of 111 microreactors could be used to
produce 1 kg of limonene 1,2-oxides 1a/b per hour, which if
operated continuously would generate around 8 tonnes of
these epoxides annually.
Conclusions
Fig. 4 Flow epoxidation of the α-pinene, β-pinene and 3-carene com-
Sustainable solvent free flow epoxidation of the di- and tri-sub-
stituted alkene bonds of various biorenewable terpenes to
produce terpene oxides has been carried out using a recyclable
tungsten-based polyoxometalate phase transfer catalyst and
ponents of untreated CST.
eliminated the noxious sulfurous odour caused by the sulfur commercial H2O2 (pH 7.0) as an oxidant. Using these continu-
impurities (e.g. Me2S, Me2S2, etc.) present in the CST feedstock ous flow epoxidation reactions in a flow reactor containing
(e.g. through oxidation to DMSO).
static mixing channels results in rapid mass and heat transfer
The yields of the eight terpene epoxides 1 and 4–10 pro- between organic and aqueous streams that leads to fast epoxi-
duced in these flow epoxidation protocols are similar (cf. 92% dation reactions and excellent temperature control. This
(batch) vs. 95% (flow) for 3-carene oxide 4), or better (cf. 63% enables epoxide products to be safely prepared in short reac-
(batch) vs. 90% (flow) for isopulegol epoxides 9a/b) than those tion times, with the flow epoxidation protocol used to produce
obtained in their corresponding batch epoxidation reactions.13 multigram quantities of limonene 1,2-oxide, with the recov-
Flow epoxidation rates for the terpene substrates were gener- ered VPT catalyst then recycled for further epoxide production
ally an order of magnitude faster than for their corresponding as required. The improved safety profile of these VPTC/H2O2
batch epoxidation reactions, with flow epoxidation reactions flow epoxidation conditions means they are better suited for
generally complete within 20 min, whilst the batch epoxidation large-scale manufacturing of epoxides than widely used bipha-
reactions required between 1–18 h to proceed. The efficiency of sic batch epoxidation conditions that suffer from potentially
these VPTC/H2O2 catalytic flow-epoxidation reactions of cyclo- dangerous thermal runaways caused by inefficient mixing and
hexene (see Table 1, entry 8) also compare favourably (e.g. poor temperature control.
lower temperature, low recyclable catalyst loadings, fast conver-
sion rates, lower equiv. of H2O2, etc.) with previous reports
where H2O2 has been used as an oxidant in catalytic flow
epoxidation reactions of alkene substrates that are liquid at
Experimental
Representative flow epoxidation procedure of (R)-(+)-limonene
ambient temperatures (see Table 1, entries 1–8 for
comparison).22–28
Two Little Things Factory (LTF) GmbH XXL-ST-04 micro-
The smaller reaction volumes, static mixing channels and reactors were connected in series using PTFE 1/16-inch tubing
heat exchangers present in the microreactors result in highly to give a total reactor volume of 10 mL (see Fig. SI1 and SI2
efficient mass transfer and excellent temperature control in ESI† for diagrams of microreactor setup). The reactor volume
these flow epoxidation reactions. This means that it should be (and residence time) could be varied by allowing the reaction
much safer to scale-up VPTC/H2O2 catalysed flow epoxidation mixture to exit at any of the sampling ports. The PW4O24[PTC]3
reactions, since it should avoid dangerous thermal runaways (2.79 g, 2259 gmol−1, 1.24 mmol, 1 mol%) catalyst33 was dis-
that can be difficult to control in large-scale batch epoxidation solved in (R)-(+)-limonene (20 mL, 16.8 g, 124 mmol, 1 equiv.)
reactions.13 The scale-up potential of this flow epoxidation pro- and then loaded into a 24 mL syringe connected to the first
tocol was demonstrated for continuous epoxidation of 13.5 mL input channel of the reactor using PTFE tubing. 30 wt%
of limonene over a 1 h period, which safely produced deca- aqueous H2O2 (20 mL, 200 mmol, 1.6 equiv.) was basified to
gram quantities of limonene 1,2-oxides 1a/b. Vacuum distilla- pH 7.0 using 3 M NaOH and then loaded into a second 24 mL
tion of the resultant crude epoxidation product enabled 9.0 g syringe connected to the second input channel of the reactor
of pure limonene 1,2-oxides 1a/b to be isolated in 71% yield. using PTFE tubing. 30 mol% of Na2SO4 (relative to terpene
The VPT catalyst recovered from this limonene flow epoxi- substrate) was added to the aqueous H2O2 stream when
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Conflicts of interest
There are no conflicts to declare.
Acknowledgements
We would like to thank EPSRC for funding through “Terpene-
based Manufacturing for Sustainable Chemical Feedstocks”
EP/K014889 and the Centre for Doctoral Training in
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30 Different catalyst precursors can be used for VPTC prepa-
ration, however varying the tungsten source and the qua-
ternary ammonium counterion did not affect the conver-
sion/selectivity in these flow epoxidations reactions. See:
D. C. Duncan, R. C. Chambers, E. Hecht and C. L. Hill,
J. Am. Chem. Soc., 1995, 117, 681–691.
produce consecutive batches of 3-carene oxide in 75–66%
yields, with small losses in catalytic activity occurring
1
between each consecutive epoxidation reaction. H and 31P
NMR spectroscopic analysis of catalyst recovered after the
third recycle indicated the presence of significant amounts
of high boiling/oligomeric/polymeric terpene species and
losses in POM counter-anion that are likely to be respon-
sible for catalyst deactivation. See ref. 13 and 30.
31 K. Sato, Y. Kon, H. Hachiya, Y. Ono, K. Takumi,
N. Sasagawa and Y. Ezaki, Synthesis, 2012, 1672–1678.
32 Previous batch epoxidation catalyst recycling studies 33 For a procedure describing the decagram scale synthesis of
revealed that the VPTC could be recycled three times to
the VPTC used in this flow epoxidation study, see ref. 13.
This journal is © The Royal Society of Chemistry 2021
Green Chem., 2021, 23, 5449–5455 | 5455