Continuous Production of Biorenewable, Polymer-Grade Lactone Monomers through Sn-Β-Catalyzed Baeyer–Villiger Oxidation with H2O2

Article abstract of DOI:10.1002/cssc.201701298

The Baeyer–Villiger oxidation is a key transformation for sustainable chemical synthesis, especially when H₂O₂ and solid materials are employed as oxidant and catalyst, respectively. 4-substituted cycloketones, which are readily available from renewables, present excellent platforms for Baeyer–Villiger upgrading. Such substrates exhibit substantially higher levels of activity and produce lactones at higher levels of lactone selectivity at all values of substrate conversion, relative to non-substituted cyclohexanone. For 4-isopropyl cyclohexanone, which is readily available from β-pinene, continuous upgrading was evaluated in a plug-flow reactor. Excellent selectivity (85 % at 65 % conversion), stability, and productivity were observed over 56 h, with over 1000 turnovers (mol product per mol Sn) being achieved with no loss of activity. A maximum space–time yield that was almost twice that for non-substituted cyclohexanone was also obtained for this substrate [1173 vs. 607 g(product) kg(catalyst)^?1 cm^?3 h^?1]. The lactone produced is also shown to be of suitable quality for ring opening polymerization. In addition to demonstrating the viability of the Sn-β/H₂O₂ system to produce renewable lactone monomers suitable for polymer applications, the substituted alkyl cyclohexanones studied also help to elucidate steric, electronic, and thermodynamic elements of this transformation in greater detail than previously achieved.

Full text of DOI:10.1002/cssc.201701298

Accepted Article
Title: Continuous production of bio-renewable, polymer-grade lactone
monomers through Sn-β catalysed Baeyer-Villiger oxidation with
H2O2
Authors: Keiko Yakabi, Thibault Mathieux, Kirstie Milne, Eva M Lopez-
Vidal, Antoine Buchard, and Ceri Hammond
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To be cited as: ChemSusChem 10.1002/cssc.201701298
Link to VoR: http://dx.doi.org/10.1002/cssc.201701298
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Continuous production of bio-renewable, polymer-grade lactone
monomers through Sn-β catalysed Baeyer-Villiger oxidation with
H2O2
Keiko Yakabi,[a] Thibault Mathieux,[a] Kirstie Milne,[a] Eva M. López-Vidal,[b] Antoine Buchard [b] and Ceri
Hammond*[a]
The Baeyer-Villiger oxidation is a key transformation for sustainable
chemical synthesis, especially when H2O2 and solid materials are
employed as oxidant and catalyst, respectively. We demonstrate that
4-substituted cycloketones, readily available from renewables,
present excellent platforms for Baeyer-Villiger upgrading. Such
substrates exhibit substantially higher levels of activity, and produce
lactones at higher levels of lactone selectivity at all values of
substrate conversion, relative to non-substituted cyclohexanone. For
4-isopropyl cyclohexanone, readily available from β-pinene,
continuous upgrading was also evaluated in a plug flow reactor.
Excellent selectivity (< 90 % at 65 % conversion), stability and
productivity were observed over 56 h, with over 1000 turnovers (mol.
product / mol. Sn) being achieved with no loss of activity. A
maximum space-time yield almost twice that obtained for non-
substituted cyclohexanone was also obtained for this substrate
(1173 vs. 607 g (product) kg-1 (cat) cm-3 (reactor) h-1). The lactone
produced is also shown to be of suitable quality for ring opening
polymerisation. In addition to demonstrating the viability of the Sn-
β/H2O2 system to produce renewable lactone monomers suitable for
polymer applications, the substituted alkyl cyclohexanones studied in
this work also allowed us to probe the steric, electronic and
thermodynamic elements of this transformation in greater detail than
previously achieved.
utilisation is strongly limited by their cost and intrinsic properties,
particularly their lack of functionalisation. Accordingly, the
development of new bio-based polymers with high degrees of
functionality represents a significant challenge.
The first step in tackling this great challenge involves the
development of new bio-based monomer structures, preferably
with tailored physical properties. Substituted ε-caprolactones (R-
Capr) are valuable monomer building blocks to a variety of
versatile functional polyesters, as well as elastomers via block
copolymerisation with lactic acid,4 with potential employment in
pharmaceutical and medical applications due to their
biocompatibility, and favourable mechanical and chemical
properties.5 A broad palette of biomass sources is suitable for
renewable monomer formation. For example, naturally available
terpenes and terpenoids, such as β-pinene or ᴅ-limonene, have
successfully been reported as precursors for substituted ε-
caprolactones.6 Lignin, the largest renewable feedstock for
aromatic compounds, has also been revealed to be a promising
source for substituted ε-caprolactones.7 Despite their differing
pathways, both routes share a common final step, where a
substituted cyclohexanone (R-CyO) is converted via Baeyer
Villiger oxidation (BVO) into the corresponding lactone monomer.
In this kind of sustainable processes where multiple steps are
required, optimisation of each step is crucial to minimise costs
and maximise productivity and selectivity. The study of the final
steps i.e. the BVO of substituted ketones, and polymerisatno of
the resulting lactones, represent the focus points of this work.
Introduction
The use of commodity polymers, such as polyesters and
polyolefins, is widespread in our society. Their range of
applications is highly varied, and includes the textile, agricultural,
automotive and healthcare industries, and applications in
storage and packaging, amongst several other fields. Such
materials are highly desired as they are light, strong and cheap.
In light of this, over 300 Mt a-1 of plastics are produced globally.1
At present, almost all polymeric materials are based on fossil
feedstock. Due to the finite nature of fossil feedstock and its
negative environmental impact, the use of sustainable resources
for polymeric materials has gathered increasing attention.2
Whilst the development of poly(lactic acid), a biodegradable
polymeric material produced from renewable lactic acid,
represents a significant breakthrough, such bio-based and bio-
degradable polymers currently only account for < 1 % of
polymers produced on an annual basis.3 Moreover, their
[a]
[b]
K. Yakabi, T. Mathieux, K. Milne, Dr. C. Hammond
Cardiff Catalysis Institute, Cardiff University,
Main Building, Park Place, Cardiff, CF10 3AT, UK
E-mail: hammondc4@cardiff.ac.uk; Web:
http://blogs.cardiff.ac.uk/hammond; Tel: +44 (0) 29 2087 6002
Dr E. López-Vidal, Dr. A. Buchard
Figure 1. Scheme of reaction for terpenes and lignin valorisation to
renewable polyester.
a
Centre for Sustainable Chemical Technologies (CSCT), Department
of Chemistry, University of Bath, Bath, BA2 7AY, UK
The BVO of ketones to lactones and esters has been widely
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10.1002/cssc.201701298
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studied over the past 100 years.8 With the aim of increasing the
sustainability of this reaction, traditionally used peracid-based
oxidants, such as peracetic acid,9 have recently been replaced
by hydrogen peroxide (H2O2), a green oxidant with several
cyclohexanones were explored as substrates. Understanding
the effect of substituents at different positions (2- and 4-) is of
high importance in order to anticipate the viability of the system
to convert more complex substrates, such as terpene-derived
ketones such as 4-isopropylcyclohexanone, into renewable
lactones. With this aim, we first investigated the impact of
increasing the size of substituent for alkyl-cyclohexanones (-Me,
-Eth, -iPr and -tBu) substituted in position 2 (2-R-CyO) and 4 (4-
R-CyO). All substrates were evaluated for BVO under our
standard reaction conditions (internal solution temperature
100°C, 0.33 M substrate in 1,4-dioxane, 1 mol % of cat,
ketone:H2O2 ratio of 1.5), and their intrinsic activity profiles
compared to non-substituted CyO.13
favourable
properties.10
Amongst
several
suitable
heterogeneous catalysts, the Lewis acidic silicate, Sn-β, has
been shown to be an excellent catalytic material for this reaction,
suitably polarising the carbonyl group and making it more
susceptible to the nucleophilic attack. Since the first report of its
activity for this reaction,11 this catalytic system has received
increasing amounts of attention. Although several studies have
focused on this system for one particular substrate
(cyclohexanone, a precursor to ε-caprolactone),12 the general
applicability and scalability of the system remain relatively
unexplored. Moreover, control of the lactone selectivity,
particularly at high levels of conversion, remains a formidable
challenge, due to unavoidable ring opening hydrolysis resulting
in hydroxyacid formation.13
Motivated by these challenges, and the possibility of
employing this system as a sustainable step towards the
catalytic generation of renewable lactones from biomass
sources (Vide Supra), the focus points of this work are to 1)
identify the general applicability of the Sn-β/H2O2 BVO system,
particularly in terms of substrate scope, 2) further evaluate its
activity, selectivity and stability in the continuous regime,
particularly for renewable-based ketones, and 3) probe the
suitability of the lactones produced during catalysis for
downstream applications.
Figure 2. Scheme for the BVO of 2-R and 4-R-substituted cyclic ketones.
Despite the similar chemical nature of the substrates tested,
large differences in reactivity within each series, and between
both series, were observed (Figure 3). For 2-R-CyO, catalytic
activity was found to decrease with increasing size of R,
decreasing from an initial turnover frequency (TOF) of ± 200 h-1
for CyO, to < 10 h-1 when the bulkiest substrates (iPr and above)
were screened (Figure 3). We note that TOF was calculated
over the first 10 minutes of reaction as mol. ketone converted /
mol. Sn per unit time. In contrast, excellent performance was
observed for 4-R-CyO at all sizes of substituent. Indeed, initial
TOF increased by some 50 % across the series, from ± 200 h-1
for CyO to > 300 h-1 for 4-tBu-CyO.
Results and Discussion
Catalyst synthesis and characterisation.
In line with our recent studies, including those focused on the
BVO of cyclic ketones, microporous Sn-β was prepared by solid
state incorporation (SSI).12a A Sn loading of 2 wt. % was
employed, as this loading results in a material possessing a
uniform distribution of isolated Sn(IV) species, with negligible
amounts of tin oxides (SnOx) being present.12a Where
appropriate, hierarchical Sn-β (Sn-β-H) was also synthesized.
This material possesses a combination of micro- and meso-
pores, resulting in improved molecular transport and greater
substrate accessibility.14 According to our optimised synthesis
protocols, Sn-β and Sn-β-H catalysts were prepared from
350
H
300
250
200
150
100
50
Me
Eth
iPr
tBu
commercially available Al-β (SiO2/Al2O3
= 38), following
dealumination in HNO3 or desilication in NaOH and
dealumination, respectively.
Both materials were extensively characterized in recent
studies,15 and for brevity the spectroscopic data will not be
reproduced in the main text. Briefly, the post-synthetic
treatments employed (dealumination, or desilication followed by
dealumination for Sn-β and Sn-β-H, respectively) did not change
the parental zeolite beta structure (ESI Figure S1-2) and Sn (IV)
was successfully incorporated in the zeolite framework almost
exclusively for both materials, as evidenced by 119Sn MAS NMR
and DRIFT studies with CD3CN (ESI Figure S3-4).
0
2-R-CyO
4-R-CyO
Figure 3. Initial TOF (10 min) obtained for the two series of BVO reactions: 2-
R-CyO (left) and 4-R-CyO (right). TOF calculated as moles of R-CyO
converted per mole Sn per time. Reaction conditions: 10 ml of 0.33 M of R-
CyO in 1,4-dioxane, 1.5 H2O2:R-CyO, 1 mol % Sn at 100 °C.
Density Functional Theory (DFT) studies (ESI Table S1)
indicate that whilst the BVO reaction of cyclohexanones into
lactones is strongly thermodynamically favoured, alkyl
substitution does not influence the overall thermodynamics of
Extending the substrate scope: Effect of 2- and 4-
substitution on catalytic activity
To evaluate the general applicability of the Sn-β/H2O2 BVO
system beyond cyclohexanone,
a
range of substituted
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the reaction. Hence, kinetic and/or steric factors must account
for the observed changes in reactivity. Although the position and
identity of the substituent will evidently impact the kinetic
diameter of each substrate, it is unlikely that overall steric bulk
and, hence, transport limitations account for the reactivity trends
within, and between, each series. This was confirmed by the
observation that hierarchical Sn-β, which also possesses
mesopores < 8 nm in diameter and has been shown to catalyse
the conversion of 12-membered cycloketones,15b gave rise to the
same trends in relative reactivity (ESI Figures S5-7). Clearly,
more localised effects are present.
The 4-R-AcetoPhO series was also screened employing Sn-
β-H as catalyst, as additional mesoporous may decrease
potential transport contributions for the bulkiest substrates. As
with Sn-β, however, electron-donating R enhanced catalytic
performance of BVO reaction with respect to acetophenone (ESI
Figure S9). The Hammett plot obtained from initial rates using
Sn-β-H also showed a similar trend to conventional Sn-β, but
with slightly improved linearity.
Although not truly conjugated, both electronic and localized
steric effects could contribute to the decrease in activity within
the 2-R-CyO series at increasing size of R. To investigate
possible electronic contributions in the BVO reaction of our
substrates of study, we selected a range of ρ-substituted
acetophenones (4-R-AcetoPhO) as model substrates. Such
substrates possess an electronically delocalized phenone ring,
which can be activated or deactivated by the para-substituent.
This can enhance or decrease its general activity for the BVO
reaction depending on the potential electronic contributions
present. In addition to providing a system by which potential
electronic effects can be elucidated, the R-phenyl acetates
generated by BVO are an attractive source for phenol derivative
formation via ester hydrolysis.16
Figure 5. Hammett plot obtained from BVO of 4-R-AcetoPhO with Sn-β (left)
and Sn-β-H (right). Reaction conditions: 10 ml of 0.33 M of 4-R-AcetoPhO in
1,4-dioxane, 1.5 H2O2:4-R-AcetoPhO, 1 mol % Sn at 100 °C.
Although unexpected based on the hypothesised reaction
mechanism, the Hammett correlation obtained agrees with
previous studies of classical BVO chemistry with peracid-based
oxidants.18 In said systems, the presence of an electron-
donating group in the para-position results in two opposite
effects: whilst it decreases the electrophilicity of the carbonyl
group, it also increases the basicity of the carbonyl oxygen,
facilitating its protonation. Once protonated, the electrophilicity of
the carbonyl group is increased dramatically, thus favouring
attack by the oxidant. Despite of the differences with our system,
the same principle can be invoked here; Given that the Lewis
acid Sn sites of the catalyst need to coordinate to, and
subsequently polarize, the C=O bond of the substrate to
promote nucleophilic attack of H2O2, it may be that electron-
donating R groups enhance coordination of the substrate,
facilitating attack by the oxidant.
Regardless of the mechanistic consequences, the
acetophenone results clearly demonstrate that potential
electronic effects cannot account for the decrease in activity at
increasing size of R in 2-R-CyO, since an increase in BVO rate
would be expected across the series based purely on electronic
factors. In view of this, it is likely that the increasing bulk of R in
the second position hinders the reaction through steric
contributions. Indeed, it can be anticipated that coordination of
the C=O group to the Sn sites within the zeolite framework will
be hindered greatly by the presence of a bulky R group in the
second position. However, this effect is likely to be very
dependent upon the precise speciation, composition and
properties of the catalyst, particularly the precise T-site location
of the Sn atoms, and is therefore likely to be strongly influenced
the preparation methodology, especially since Sn-β samples
prepared by hydrothermal synthesis exhibit different trends.7b
Figure 4. BVO of 4-R-AcetoPhO, including potential downstream valorisation
of the resulting R-phenyl acetates.
The effect of various electron-donating (Hammet constant
value (σ) < 1) and electron-withdrawing substituents (σ > 1),
were studied under standard BVO conditions with microporous
Sn-β as catalyst. Considering the most widely accepted reaction
mechanism, based on
a two-step reaction first involving
nucleophilic attack of the oxidant to the carbonyl group forming a
Criegge adduct, and subsequent migration resulting in the BVO
product,17 we hypothesized that a decrease of the BVO rate
should be observed when electron-donating R groups are
present, due to lower electrophilicity at the carbonyl carbon atom.
However, detailed kinetic analysis revealed that the opposite
trend for all 4-R-AcetoPhO substrates tested occurred. Electron-
donating R groups (-NH2, -OAlkyl and -Alkyl) enhanced activity,
whilst electron-withdrawing R groups (-Cl and -NO2) decreased
the rate substantially. For instance, the presence of -NH2, the
highest electron-donating R tested, improved conversion of
acetophenone from 8% to 60% after 6h of reaction. In contrast, -
NO2, the most electron-withdrawing R group, deactivated the
substrate completely (ESI Figure S8). A typical Hammett plot
further supported the observed electronic effect. Although the
trend obtained was not completely linear, in general terms,
higher electron-donating ability resulted in higher initial rates of
BVO with respect to acetophenone.
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Given that Sn-β also catalyses the hydrolysis of the lactone
product, we considered the possibility that pore size limitations
experienced by the bulkier 4-R-Capr products may inhibit their
access the Sn sites following BVO, thus decreasing consecutive
ring opening. To evaluate this hypothesis, the conversion-
selectivity profile obtained for the BVO of CyO, 4-Eth-CyO and
4-iPr-CyO over Sn-β-H and Sn-β were compared. If confinement
and pore size limitations were key to inhibiting the interaction of
the product lactone and the Sn sites, hydrolysis of the lactone
should be more dramatic when using the hierarchical catalyst.
Nevertheless, no significant differences in terms of activity or
selectivity were observed for the three substrates when using
Sn-β-H (Figure 6, Right), and the selectivity trends to substituted
lactones using both materials were maintained i.e. higher
lactone selectivity was still observed even when mesopores < 8
nm are present.
Extending the substrate scope: Effect of 2- and 4-
substitution on reaction selectivity
In addition to increased activity, substitution of the cyclohexane
ring results in major changes in reaction selectivity, especially
for the 4-R-CyO series. In our previous studies focused on the
BVO of CyO with Sn-β/H2O2,13 we demonstrated that a decrease
in lactone selectivity occurs as the level of ketone conversion
increases beyond approximately 60 %. This occurs through
hydrolysis of the lactone product, resulting in the formation of the
corresponding hydroxyacid (6-hydroxyhexanoic acid (6-HHA) in
the case of CyO). In addition to decreasing selectivity, the
hydroxyacid product also deactivates the catalyst by poisoning.
Unfortunately, our previous work revealed the consecutive ring
opening reaction to be unavoidable for CyO, as it is also
catalysed by Sn-β. The unavoidable formation of the ring-
opened hydroxyacid is currently a major limitation of the Sn-
β/H2O2 system for ε-caprolactone formation.
To investigate the impact of alkyl substitution on reaction
selectivity, we monitored lactone selectivity as a function of
substrate conversion for
a variety of substituted ketone
substrates. Due to their rapid rates of reaction, we primarily
focused upon 4-substituted ketones (4-R-CyO). As can be seen
(Figure 6, Left), the lactone selectivity obtained for each
substrate is generally higher at all overlapping levels of
conversion, following substitution at the 4 position. The improved
selectivity is especially notable at high levels of conversion,
where the consecutive hydrolysis reaction occurs more readily.
Indeed, lactone selectivity at particular levels of conversion
increases as the size of the 4-R substituent increases. For
example, whilst the lactone selectivity decreased to < 50 % at a
conversion of 80 % for CyO, lactone selectivity for both 4-iPr-
CyO and 4-tBu-CyO remained above 80 % throughout the
reaction profile, and becomes independent of the extent of
conversion. Quantification of all the reaction products confirms
that ring opening hydrolysis accounts for the remaining carbon
balance for each substrate (ESI Figure S10-12). Given the
negative role of hydroxyacids in the Sn-β/H2O2 system (Vide
Supra), the outstanding results obtained for 4-R-CyO, especially
in terms of high lactone selectivity at high levels of conversion,
points towards them as being especially promising substrates for
renewable lactone formation.
Figure 7. Caprolactone (left) and 4-iPr-Capr (right) hydrolysis performed with
Sn-βa, Sn-β-Ha and H2SO4b. Reaction conditions: 10 ml of 0.2 M of lactone in
1,4-dioxane, 0.15 ml of H2O, 1 mol % Sn and H2SO4 equivalent to usual 1
mol % Sn used, at 100 °C.
a
b
To verify that the substituted lactone products are
intrinsically more resistant to ring opening, and that pore size
limitations do not decrease the extent of hydrolysis through
steric effects, a study of the hydrolysis of isolated 4-iPr-Capr was
performed. Three catalysts (Sn-β, Sn-β-H and H2SO4) were
screened for hydrolysis activity using the same amount of water
as present in a typical BVO reaction from aqueous H2O2. If pore
size limitations were responsible for the decreased levels of
hydrolysis that occurs to 4-iPr-Capr, then one would expect
hydrolysis to occur more readily for Sn-β-H, which is hierarchical
in nature and possesses
a combination of micro- and
mesopores. Although both heterogeneous catalysts are less
active than H2SO4, it is clear that the co-presence of mesopores
is not at all beneficial to the rate of hydrolysis, as the rate of
hydrolysis is similar, if not lower, when hierarchical Sn-β-H is
employed as catalyst. It is also notable that the rate of hydrolysis
of 4-iPr-Capr is much lower than that of Capr even when a
homogeneous catalyst is employed. Since there are no
confinement issues present for the homogeneous system, the
decreased rates of hydrolysis observed between Capr and 4-iPr-
Capr confirms that the substituted lactones is more resistant to
hydrolysis. Further verification of this was achieved through a
Figure 6. Selectivity to 4-R-lactone as function of 4-R-CyO conversion (left)
and selectivity to lactone obtained with Sn-β and Sn-β-H as function of
conversion of 4-R-cyclohexanone (right), where R is defined in the figure
legend.
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thermodynamic study of the hydrolysis reaction with DFT (ESI
Table S2). These calculations were consistent with the
experimental data, indicating that increasing substitution at the
Indeed, the maximal space-time-yield obtained during the BVO
of 4-iPr-CyO is almost two-times higher than that obtained during
the BVO of CyO (1173 vs. 607 g kg-1 cm-3 h-1, respectively).
Thus, in addition to being a renewable and sustainable source of
carbon for chemical production, 4-substituted ketones such as 4-
iPr-CyO are more active, selective and productive substrates for
BVO chemistry.
4-position
makes
hydrolysis
more
thermodynamically
unfavoured, despite the substitution being relatively remote from
the lactone function. We note here, therefore, that the hydrolysis
reaction is clearly disfavoured for substituted lactones for both
thermodynamic (DFT) and kinetic (experimental) reasons.
Probing lactone quality: Polymerisation studies
Extending the substrate scope: Intensification of 4-iPr-CyO
BVO in continuous flow
To demonstrate the viability of the lactone produced through this
BVO process for polymer formation, ring opening polymerization
of 4-iPr-Capr, isolated by simple column chromatography, was
performed under industrially relevant melt conditions at 110 °C,
using triazabicyclodecene (TBD) as catalyst (1 mol. %) and 4-
methylbenzyl alcohol (1 mol. %) as initiator. Previously, only
metal-catalysed polymerisation has been reported for such
substrates. After a period of 24 h, 30% conversion was observed.
The produced polymer possessed an average molecular weight
number (Mn) of 1384 g mol–1, and 1.27 dispersity, clearly
demonstrating that the lactone produced through BVO is
suitable for polymer applications even without excessive pre-
treatments. Future studies will further explore the potential of
monomers produced through this BVO process for polymer
formation.
Given that 4-substituted ketones, such as 4-iPr-CyO, are more
active for BVO, are more resistant to undesirable hydrolysis, and
are also available from renewable resources such as β-pinene,
they appear to be especially promising substrates for BVO
upgrading. Accordingly, intensification of the BVO of 4-iPr-CyO
was investigated in the continuous regime with Sn-β as catalyst.
Performance, in terms of stability and productivity (space-time-
yield) was compared to that obtained during the BVO of CyO.
After a short induction period, during which both activity
and selectivity increase, both systems (CyO and 4-iPr-CyO)
reach a steady state level of performance over the reaction
period explored (56 h), with little or no loss of activity being
observed. Selectivity continues to increase during the initial
cycle, reaching a maximum of ± 85 % after 50 h of operation.
During this period, > 1000 turnovers (mol. product / mol. Sn) are
achieved for 4-iPr-CyO, equivalent to > 10 batch reactions under
typical conditions. This clearly demonstrates the stability of the
Sn-β/H2O2 catalytic system for the BVO of more functionalized
starting substrates.
Conclusions
4-substituted cycloketones, such as 4-isorpopyl cyclohexanone
(4-iPr-CyO), are readily available from a variety of renewable
resources, including terpenes and lignin. Herein, we show such
substrates are especially favourable as platforms for Baeyer-
Villiger oxidation, which is a key step in the production of
renewable lactone monomers. In addition to being renewable,
we show that such substrates are also more active, more
selective and more productive substrates for BVO relative to
non-substituted cycloketones such as cyclohexanone. Optimal
performance was observed for 4-isorpopyl cyclohexanone,
which could be continuous oxidised to the corresponding lactone
at high conversion (< 80 %), selectivity (< 80 %) for over 60 h on
stream, corresponding to over > 1000 substrate turnovers. In
this case, the maximal space-time yield was almost twice that
obtained during BVO of cyclohexanone, reaching 1173 g
(product) kg-1 (catalyst) cm-3 h-1, at a lactone selectivity of 85 %.
Various electronic, steric and thermodynamic effects are shown
to contribute to the outstanding reactivity of such substituted
cyclic ketones for Baeyer-Villiger oxidation. The lactone
produced by this continuous experiment is also shown to be
suitable for downstream polymerisation, being effectively
polymerized at mild, metal-free conditions.
Figure 8. Space-time yield obtained for BVO of CyO and 4-iPr-CyO in
continuous operation (left). Space-time yield calculated as
g of lactone
produced per kg of catalyst per reactor volume per time. Selectivity to lactone
as function of conversion (right). Reaction conditions: Reactant feed of 0.33 M
cyclohexanone and 0.5 M H2O2 in 1,4-dioxane with a contact time of 5.5 min
under a pressure of 10 bars, at 100°C.
The outstanding results obtained in both batch and
continuous mode clearly demonstrates the successful
broadening of the substrate scope of the Sn-β/H2O2 BVO system.
Moreover, it opens a route towards the sustainable production of
renewable monomers through the BVO of sustainably derived
ketones.
Although both systems exhibit comparable levels of
stability, it is notable that under identical conditions, the
continuous BVO of 4-iPr-CyO results in higher levels of activity
(conversion) and selectivity (Figure 8, Right). In addition to
corroborating the batch results (Vide Supra), the increased
levels of activity and selectivity combine to yield substantial
improvements in space-time-yield over the reaction period.
Experimental Section
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Catalyst synthesis. Sn-β catalyst was prepared as follows:
Continuous BVO reactions were performed in a home-made
plug flow, stainless steel, tubular reactor. Reactant delivery (0.33
M R-CyO in 1,4-dioxane, H2O2:ketone = 1.5) was performed by
an HPLC pump. The catalyst (0.2 g) was mixed with a diluent
material (SiC (particle size of 63-75 µm), 0.8 g) in order to avoid
back mixing and to minimize pressure drop, and the bed placed
in between two plugs of quartz wool. The diluted catalyst was
densely packed into a ¼” stainless steel tube (4.1 mm ID), and a
frit (0.5 µm) was placed at the end of the bed to avoid any loss
of material. A contact time of 5.5 min was typically employed.
The reactor temperature was controlled by immersion in a
thermostatic oil bath, and pressure was controlled by means of a
backpressure regulator (10 bars). The reaction feed was
identical to that used for batch reactions. Aliquots of the BVO
reaction solutions were taken periodically from a sampling valve
placed after the reactor, and were analysed in the same manner
as the batch reactions.
Zeolite Al-β (Zeolyst, NH4-form, SiO2/Al2O3
=
38) was
dealuminated by treatment in HNO3 solution (13 M HNO3, 100
ºC, 20 h, 20 mL g-1 zeolite). The dealuminated powder was
washed with water and dried overnight at 110 ºC. Solid-state
stannation was performed by grinding the appropriate amount of
tin (II) acetate with the necessary amount of dealuminated
zeolite for 10 minutes in a pestle and mortar, prior to heat
treatment in a combustion furnace (Carbolite MTF12/38/400). A
two stage heat treatment was employed: to 550 ºC (10 ºC min-1
ramp rate) first in a flow of N2 (3 h not including ramp period)
and subsequently air (3 h) for a total of 6 h plus heating and
cooling periods. Gas flow rates of 60 mL min-1 were employed at
all times. The sample was held horizontally in an alumina
combustion boat (10 mL capacity), and a quartz tube was used
to seal the sample environment.
Sn-β Hierarchical (Sn-β-H) was prepared as follows:
Commercial Al-β Zeolite (CP814E, NH4-form, SiO2/Al2O3 = 38,
Zeolyst International) was first converted into protonic form by
calcination in static air at 550 °C (5 °C min-1) for 5 h. The H-form
zeolite was subsequently suspended in an aqueous solution of
NaOH (0.2 M, 318 K, 0.5 h, 30 mL g-1 zeolite) to obtain a
i
Polymerisation. In a glovebox, 4- PrCapr (0.35 g, 2.2
mmol), triazabicyclodecene (22 µL of 1 mol L–1 solution in
anhydrous DCM), 4-methylbenzylalcohol (22 µL of 1 mol L–1
solution in anhydrous DCM) were mixed and sealed in flask
under argon, before transferring to an oil bath preheated at
110 °C. After the required time, the flask was opened to air,
quenched with a few drops of MeOH and the solvent removed in
vacuo. A crude NMR was recorded to determine conversion of
monomers from the relative integrals of monomer and polymer
resonances.6 The polymer was then washed with MeOH to
remove unreacted monomer before drying under vacuum and
analysis by Size-Exclusion Chromatography (SEC). SEC was
carried out on an Agilent Technologies 1260 Infinity instrument
with a flow rate of 1 mL min–1 at 35 °C with a THF eluent and
referenced against polystyrene standards (RI).
desilicated zeolite
β (deSi-β). The reaction was stopped
immediately by cooling the container in an ice bath. The
remaining solid product was centrifuged, thoroughly washed with
deionized water until neutral pH was attained, and finally dried at
373
K overnight. Subsequently, deSi-β was dealuminated
following the same procedure described above. After filtering
and drying the sample, the sample was reconverted into NH4-
o
form via ion exchange in a solution of NH4NO3 (1 M, 2 h, 85 C,
30 mL solution g-1 (catalyst). Solid-state incorporation of Sn was
performed as described above.
Kinetic evaluation and analytical methods. Batch BVO
reactions were performed in a 100 mL round bottom flask
equipped with a reflux condenser. Reaction temperature was
controlled by immersion in a silicon oil bath. The vessel was
charged with a 10 mL solution of substrate in 1,4-dioxane (0.33
M), which also contained an internal standard (biphenyl, 0.01M),
and the appropriate amount of catalyst. The vessel was
subsequently heated to the desired temperature (100 ºC internal
temperature). The reaction was initiated by addition of an
appropriate amount of H2O2 (50 wt% in aqueous solution),
typically corresponding to a H2O2:ketone ratio of 1.5. The
solution was stirred at ± 750 rpm with an oval magnetic stirrer
bar. Aliquots of reaction solution were taken periodically for
analysis, and were centrifuged prior to injection into a GC
(Agilent 7820, 25m CP-Wax 52 CB). Reactants were quantified
against a biphenyl internal standard. Quantification of the by-
products by 1H NMR was achieved by calibrating a capillary
containing a known amount of tetramethylsilane (TMS) (s, δ= 0.0
ppm) against known standards, and placing this capillary within
the NMR tubes of various time online samples.
Computational details. All calculations were performed
using the Gaussian09 suite of codes (revision D.01).19
Geometries were fully optimised without any symmetry or
geometry constraints using various functional (ωB97XD,20
B3LYP-D321 and M06-2X).22 Calculations were carried out using
a temperature of 398.15 K and solvent effects in 1,4-dioxane
were considered using a conductor-like polarisable continuum
model (CPCM).23 The nature of all the stationary points as
minima was verified by calculations of the vibrational frequency
spectrum. Free energies were calculated within the harmonic
approximation for vibrational frequencies. Only the most stable
conformational isomers are reported for all intermediates.
Acknowledgements, funding sources and
contributions
Acknowledgements. CH gratefully acknowledges support
of The Royal Society for provision of a University Research
Fellowship (UF140207) and additional research grant funding
(RG140754). AB gratefully acknowledges Roger and Sue
Whorrod (Whorrod Research Fellowship) and the University of
Bath HPC facilities. KY, AB and CH appreciate the support of
the EPSRC for provision of a PhD studentship to KY as part of
the EPSRC-funded Catalysis CDT, 2014-2018.
R-Caprolactones were obtained as colourless oils from the
BVO
reactant
solutions
and
separate
by
column
chromatography (silica gel, Hexane:Ethyl acetate = 3:1). Batch
R-caprolactone hydrolysis reactions were performed following
the same procedure and reaction conditions as used for the
BVO reaction, although R-Cyclohexanones were replaced with
R-caprolactone and oxidant was replaced with the equivalent
water amount added.
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[21] S. Grimme, J. Antony, S. Ehrlich and H. Krieg, J. Chem. Phys., 2010, 132,
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Keywords: Baeyer-Villiger oxidation • Tin beta • Heterogeneous
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[22] Y. Zhao and D. G. Truhlar, Theor. Chem. Account, 2008, 120, 215 - 241
[23] G. Scalmani and M. J. Frisch, J. Chem. Phys., 2010, 132, 114110
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Keiko Yakabi, Thibault Mathieux, Kirstie
Milne, Eva M. López-Vidal, Antoine
Buchard and Ceri Hammond*
Page No. – Page No.
Title
The continuous conversion of renewable ketones, available from pinenes and lignins, to polymer end products is
achieve through Sn-b-catalysed Baeyer-Villiger oxidation with H2O2 and metal-free ring opening polymerisation.
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