Solvent-free hydrogenation of levulinic acid to γ-valerolactone using a Shvo catalyst precursor: Optimization, thermodynamic insights, and life cycle assessment

Article abstract of DOI:10.1039/c9gc02088h

The hydrogenation of levulinic acid (LA) to γ-valerolactone (GVL) using the η⁴-(2,3,4,5-tetraphenylcyclopentadienone) ruthenium tricarbonyl precursor of the well-known Shvo catalyst and H₂ pressure was established under solvent-free conditions to achieve 100% conversion and 100% selectivity within 5 hours. Kinetic reaction curves were measured in order to deduce the optimal reaction conditions, which were further evaluated by means of density functional theory (DFT) calculations, and compared with catalytic concepts that consume formic acid or isopropyl alcohol as hydrogen donor. Ultimately, this alternative reaction procedure was subjected to a life cycle assessment (LCA) in comparison with the transfer hydrogenation methodologies, in order to verify its contribution towards a practice of environmentally benign chemistry.

Full text of DOI:10.1039/c9gc02088h

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Solvent-free hydrogenation of levulinic acid to
γ-valerolactone using a Shvo catalyst precursor:
optimization, thermodynamic insights, and life
cycle assessment†
Cite this: DOI: 10.1039/c9gc02088h
Christian A. M. R. van Slagmaat,
Lukas Morick,‡ Yvonne van der Meer, * Katrien V. Bernaerts
Stefaan M. A. De Wildeman
Marie A. F. Delgove,
Jules Stouten,‡
and
*
The hydrogenation of levulinic acid (LA) to γ-valerolactone (GVL) using the η4-(2,3,4,5-tetraphenylcyclo-
pentadienone) ruthenium tricarbonyl precursor of the well-known Shvo catalyst and H2 pressure was
established under solvent-free conditions to achieve 100% conversion and 100% selectivity within
5 hours. Kinetic reaction curves were measured in order to deduce the optimal reaction conditions,
which were further evaluated by means of density functional theory (DFT) calculations, and compared
with catalytic concepts that consume formic acid or isopropyl alcohol as hydrogen donor. Ultimately, this
alternative reaction procedure was subjected to a life cycle assessment (LCA) in comparison with the
transfer hydrogenation methodologies, in order to verify its contribution towards a practice of environ-
mentally benign chemistry.
Received 21st June 2019,
Accepted 9th December 2019
DOI: 10.1039/c9gc02088h
rsc.li/greenchem
In 2004, the US Department of Energy compiled a list of
promising substrates obtainable from carbohydrates, categor-
1. Introduction
While for the past 150 years many of our fuel, drug, and izing them according to their anticipated properties in one of
material needs have been satisfied with fossil-based products, nine different fields.4 LA is one of those molecules, that was
the need to find sustainable bio-based alternatives is ever- identified as a platform molecule showing great potential for a
increasing with dwindling resources, accelerating global large variety of conversions.5 It is shown to be facilely converti-
warming, and increasing global turmoil.1 One promising ble into molecules relevant in a plethora of different appli-
source of such renewable resources is the abundant and widely cations (Scheme 1). One conversion is particularly relevant in
accessible lignocellulosic material. Much effort over the past the fields of bio-based solvents,6 fuels,7 and fuel additives:8 the
decades has gone into the development of technologies to hydrogenation of LA to GVL. In addition, other research ident-
harness the potential of this inherently complex natural ifies the high potential of this molecule as monomer for the
material, and cellulose in particular has become an efficient synthesis of polymeric materials9 and related applications, such
feedstock to produce a large variety of building blocks and as the conversion to adipic acid via (hydroxy) carbonylation with
fuels.2 Many processes such as fermentation, enzymatic depo- carbon monoxide or formic acid (FA). The high value of adipic
lymerizations, and acid-catalyzed conversions have become acid in polycondensations creates high interest in this conver-
well established in providing mono-sugars or oligomers, which sion.10 In terms of domestic applications (e.g. cosmetical pro-
in turn can be transformed further into numerous fine ducts,11 lighter- and candle fluids7), beneficial properties of
chemicals.3
GVL are its high thermal and chemical stability,12 and its plea-
sant smell.11 GVL also possesses a stereogenic carbon center,
which creates opportunities for the manufacture of pharma-
ceutical products, should enantio-selectivity be achieved.13
Over the last couple of decades, various catalytic procedures
have been established for the hydrogenation of LA to GVL.14
Heterogeneous catalysts are often preferred in chemical indus-
tries for advantages, such as facile separation and recycling.
However, various homogeneous catalysts recently have entered
the spotlights by displaying high activities and excellent – or at
Department of Biobased Materials, Aachen-Maastricht Institute for Biobased
Materials, Maastricht University, Brightlands Chemelot Campus, 6167 RD Geleen,
The Netherlands. E-mail: c.vanslagmaat@maastrichtuniversity.nl,
yvonne.vandermeer@maastrichtuniversity.nl, s.dewildeman@maastrichtuniversity.nl;
https://www.maastrichtuniversity.nl/research/department-biobased-materials
†Electronic supplementary information (ESI) available. See DOI: 10.1039/
c9gc02088h
‡These authors contributed equally to this work.
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Scheme 1 Overview of the conversion of biomass via (hemi)cellulose, furanoic platform molecules, and LA into GVL, and its various applications.
least tunable – selectivity towards GVL. Among the homo- produce stoichiometric amounts of carbon dioxide (CO2) and
geneous examples some outstanding turn-over numbers (TON) acetone, respectively. Hence, it is expected that this chemical
up to 174 000 have been reported for catalysts based on ruthe- route is environmentally more benign. Furthermore, H2 allows
nium15 and iridium16 predominantly, while iron17 has recently more parameter variation (temperature, pressure) without
made its debut.
diminishing the effective reaction volume. On the other hand,
Other homogeneous catalysts have also shown tolerance to using FA as reductant is an eclectic choice as well, since FA is
solvent-free conditions. Several in situ catalysts derived from the co-product of the synthesis of LA from 5-hydroxymethyl-
Ru(acac)3 and phosphine ligands were shown to be highly furfural (HMF) (Scheme 1), and would not require separation
efficient by the groups of Horváth,18 Leitner,19 Mika,15a,20 and before a subsequent hydrogenation step. Hence, we ques-
Beller,15b whereas full conversions to GVL were selectively tioned how the choice of hydrogen donor under solvent-free
achieved under 80–100 bar H2 pressure and temperatures of conditions affects the reaction in terms of catalytic perform-
135–160 °C. Alternatively, Deng et al. reported the transfer ance as well as environmental impact.
hydrogenation of LA using 1 equivalent of FA catalyzed by
Therefore, we established the solvent-free H2-mediated
RuCl3 with phosphine ligands.21 Other examples of transfer selective hydrogenation of LA to GVL using the monomeric
hydrogenation using FA in slight excess (less than 2 equivalents) Shvo catalyst precursor Ru-1 in this work, and optimized it in
were demonstrated with Shvo-type catalysts at a milder tempera- terms of temperature, H2-pressure, and catalyst loading. A
ture of 100 °C by Fábos et al.,22 and with dipyridyl-ligated ruthe- possibility for catalyst recycling as well as the role of water in
nium23 and iridium16c,23 catalysts by Wang et al. Moreover, the the catalytic mechanism were investigated. Computational
group of Makhubela recently reported ruthenium catalysts with DFT experiments were conducted to evaluate the thermo-
pyrazolylphosphite24 and pyridylimine25 ligands, of which the dynamic pathways of different hydrogen donors, and these
former one is able to use both FA and H2 as hydrogen donors in results were validated with the experimental observations.
low quantities of 1 equivalent and 5–20 bar, respectively, for Finally, a LCA evaluating the use of each hydrogen donor in
this conversion. The same group also synthesized polynuclear this context was performed.
Ru4^Zn2 complexes with phosphino-carboxylate ligands, which
show a remarkably improved activity for such transfer hydrogen-
ations compared to their corresponding monomeric forms.26
Previously, we reported on the comparative study of the
Shvo catalyst versus its pre-activated iron analogue, the aceto-
2. Results and discussion
2.1. Catalyst precursor syntheses and evaluation in catalysis
nitrile-appended Knölker catalyst, for the selective hydrogen- To pursue our findings regarding the activity of the Shvo-type
ation of LA to GVL.27 Herein, the catalysis was driven by the ruthenium catalysts, it was decided to test all three possible
hydrogen donors isopropyl alcohol (IPA) and H2 in various sol- precursors. These can be synthesized from triruthenium dode-
vents. Although appreciable TON’s could be achieved by using cacarbonyl and tetraphenylcyclopentadienone in refluxing
the iron catalyst, the ruthenium Shvo catalyst was significantly toluene, methanol, or heptane, to yield the monomeric
more active. However, the solvent-free form of this chemical [2,3,4,5-Ph4(η4-C4CO)]Ru(CO)3 (Ru-1), and the dimeric species
transformation using H2 reductant facilitated by the Shvo cata- {[2,3,4,5-Ph4(η4-C4CO)]2H}Ru2(CO)4-(μ-H) (Ru-2) and {[2,3,4,5-
lyst is not reported yet, and the absence of added organic sol- Ph4(η4-C4CO)]Ru(CO)2}2 (Ru-3), respectively (Scheme 2,
vents herein are envisioned as key to furtherly improve space– ‘Synthesis’).29 High yields up to 98% for Ru-1 were typically
time yields significantly, and thereby also reducing the obtained, since this compound can facilely be purified using
environmental impact of the process. While in transfer hydro- column chromatography. However, Ru-2 and Ru-3 require pre-
genation the hydrogen donor (e.g. FA, IPA) often co-functions cipitation/crystallization in order to be isolated, leading to
as a solvent and therefore may stabilize the in situ catalytic lower yields in the range of 50–60% in our hands.
species,28 the use of H2 under absolute solvent-free conditions
Exploratory hydrogenation reactions of LA using these cata-
is expected to be more challenging. Meanwhile, the use of H2 lyst precursors were conducted under solvent-free conditions
does not yield any by-products, unlike FA and IPA, which co- at 100 °C and under 50 bar H2 pressure for 5 hours.
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Alternatively, the structurally related iron Knölker-type cata-
lysts could be realized as a cheaper and greener substitute. In
our previous study we concluded the necessity of converting
Knölker’s complex (Fe-1) into its mono-decarbonylated aceto-
nitrile-appended contender Fe-2, to conveniently afford
Casey’s catalyst (Fe-3) in situ for the successful hydrogenation
of LA in a solvent (ESI, Scheme S1.1†).27 In this work we tested
Fe-2 also under solvent-free conditions, but it rapidly decom-
posed as such, and no LA conversion was observed (Table 1,
entry 8). Therefore, the focus was kept on the Shvo catalyst.
Despite the lower activity of Ru-1 compared to its dimeric
homologues, we selected this catalyst precursor for further
investigation on the basis of the synthetic yields, as well as
possible future applications of Shvo type complexes with sub-
stituents on the 2- and 5-position, which are too large to allow
the dimer formations seen for Ru-2 and Ru-3.30 In addition,
this choice gave us the opportunity to elucidate the relation
between requiring in situ decarbonylation of Ru-1 and the
inhibited LA conversion (63.0%), and how to overcome it.
Scheme 2 Overview for the solvent-mediated syntheses of the three
different Shvo catalyst precursors and their dissociation into the catalyti-
cally active species. Each synthetic pathway requires reflux conditions
under a N2 atmosphere during 24–72 hours.
2.2. Reaction parameter optimizations
The control experiments employing no catalytic additive;
only the ligand; only Ru3(CO)12; and the ligand plus Ru3(CO)12
(Table 1, entries 1–4, respectively) all rendered no conversions,
while significant activity was observed for Ru-1, Ru-2, and Ru-3
with TON’s of at least 630 (Table 1, entries 5–7). This obser-
vation confirms that the sophisticated organometallic struc-
ture of the Shvo catalyst is indeed essential to afford catalytic
activity in this reaction, and that in situ generation in LA is not
possible. Moreover, the remarkable difference in LA conver-
sion between Ru-1 (63%) and both Ru-2 and Ru-3 (>99%) can
be rationalized by the requirement of mono-decarbonylation
for Ru-1 in order to be activated (vide infra), while the dimeric
Ru-2 and Ru-3 are reported to readily dissociate at 80 °C into
monomeric ruthenium species Ru-4 and Ru-5, that are part of
the catalytic cycle (Scheme 2, ‘Activation’).22
The research was continued by establishing kinetic curves for
each experiment using 0.1% Ru-1, in order to observe the
effect of systematically altering the reaction conditions. These
experiments took place in a batch autoclave reactor, equipped
with an external heating mantle, which required
10–15 minutes to heat up the reaction mixture to the desired
temperature. Since the t = 0 point is defined as the moment
where heating was initiated, the first 15 minutes of the reac-
tion always feature minimal LA conversion.
Firstly, the reaction temperature was varied, ranging from
100 to 160 °C (Fig. 1A). While a maximal turn-over frequency
(TOF) of 144 h−1 is finally reached after 3 hours at 100 °C, a
dramatic increase in activity was achieved at 120 °C, rendering
a TOF of 598 h−1 after 30 minutes already, and reaching near-
complete conversion within 4 hours. A further increase in
activity was observed at 140 °C and 160 °C with maximal local
TOF’s around 1200 h−1. However, these reactions undergo
sudden catalyst deactivation after 60–90 minutes at LA conver-
sions of 97% and 78%, respectively. Thus, an optimal reaction
temperature of 120 °C was found for Ru-1, as in agreement
with the observation of Casey et al., that decomposition of
such complexes starts around 130 °C.31 Next, the H2 pressure
was varied from 20 to 100 bar at the optimal reaction tempera-
ture of 120 °C (Fig. 1B). In general, a higher TOF was achieved
by applying a higher H2 pressure, but a ceiling in activity was
observed at 50 bar H2 pressure and higher. Nevertheless, >97%
GVL yields were always obtained after 5 hours. As such, 50 bar
H2 was selected as the optimal pressure for this reaction.
The concentration effect of Ru-1 was investigated as well
(Fig. 1C). Higher reaction rates were observed at higher con-
centrations of Ru-1, as expected. However, the relative TOFs
increased upon lowering the catalyst loading. In order to yield
>99% GVL within the convenient time frame of 5 hours, 0.1%
Ru-1 should be maintained.
Table 1 Exploratory solvent-free hydrogenations of LA to GVL using
the Shvo precursor catalysts and several control experiments
Entrya
Catalyst precursor
GVL yield (%)
1
2b
3
4
5
6
7
8
None
Ph4CpO ligand
Ru3(CO)12
3 Ph4CpO + Ru3(CO)12
Ru-1
Ru-2
Ru-3
Fe-2
0
0
0
0
63.0
99.5
99.1
0
a Catalyst loading is always based on the amount of metal atoms.
b 0.1 mol% ligand with respect to LA.
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Fig. 1 Parameter optimizations for the solvent-free hydrogenation of LA to GVL, established by the kinetic reaction profiles. The standard con-
ditions are 120 °C, 50 bar H2 (hot pressure), 0.1 mol% Ru-1, unless indicated otherwise. The investigated parameters concern (A) reaction tempera-
ture; (B) H2 pressure; (C) catalyst loading; (D) catalyst precursor using 0.1% Ru atoms.
Finally, to retrospectively assess our choice to use Ru-1 in Karl-Fischer titration of the used LA stock revealed a water con-
this study, we applied the optimized conditions using Ru-2 centration of 2022 ppm, which equals 0.002 equivalent with
and Ru-3 (Fig. 1D). These two dimeric species were observed to respect to LA. It is plausible this initial presence of water
become much more readily active within the first 30 minutes indeed activates a part of the present Ru-1 into Ru-4 upon
than Ru-1, although keeping in mind that the slower LA con- heating. As such, the LA hydrogenation can be enabled, so
version within the first 15 minutes most likely corresponds to that the H2O concentration accumulates further, and pushes
the heating ramp of the autoclave. Consequently, the reactions the Ru-1 decarbonylation to completion, as observed in the
catalyzed by Ru-2 and Ru-3 finish 1 hour earlier compared to kinetic curves.
Ru-1. However, their maximal TOF’s render 711 and 678 h−1
respectively, which is in the same order of magnitude com-
,
2.3. Catalyst recycling studies and the effect of water
pared to the rate observed for Ru-1. Hence, despite their Attempts to recycle the catalyst were conducted in a similar
immediate activation, Ru-2 and Ru-3 do not bear significant manner as earlier reported by Fábos et al.22 Careful vacuum
advantages over Ru-1 in terms of catalytic activity.
distillation of the reaction mixture yields water (50 °C,
The sigmoidal curves observed for Ru-1 throughout these 40 mbar) first, and then GVL (90 °C, 1 mbar). The catalyst
kinetic studies could be rationalized further by build-up of remains in the residue as an orange solid along with a trace
water over the course of the hydrogenation reaction, which is amount of GVL or unreacted LA, and is dissolved in fresh LA
proposed as a suitable decarbonylative agent for Ru-1,28,32 as for recycling. Unfortunately, after the successful run with fresh
well as for Fe-1.33 Since numerous examples of such catalyst catalyst, the conversion of the first and second recycles
decarbonylations are described using various bases34 or tri- decreased to 85% and 36%, respectively. This result was sur-
methylamine oxide,35 a similar mechanism can be realized prising, since Fábos et al. reported three successful recycles of
with water acting as an Arrhenius base (ESI, Scheme S1.2†). A Ru-2 without loss of activity.22 Therefore, several possibilities
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were considered, that may have caused catalyst deactivation in
our hands.
Firstly, we focused on ascribing this problem to either our
hydrogenation procedure, or to the catalyst recovery. To
exclude the possibility of catalyst deactivation by exposure to
oxygen upon opening the autoclave after the regular reaction
time of 5 hours, a 32 hours long experiment with 0.005% Ru-1
at 120 °C and 50 bar H2 was devised, in order to either
confirm or dismiss an increased activity compared to the
cumulative TONs of the recycling experiments. This reaction
rendered a total TON of 9140, upon which a plateau was
observed after 10 hours, confirming catalyst deactivation (ESI,
Fig. S2.1†). This result suggests a certain aspect in the present
hydrogenation procedure to be the critical factor in causing
catalyst deactivation.
Fig. 3 Recycling studies of Ru-1 in the hydrogenation of LA and EL.
Conditions: 0.1% Ru-1 in LA (neat) under 50 bar H2 pressure at 120 °C.
In an attempt to elucidate the catalyst deactivation on mole-
cular level, the catalysts used in one run were isolated in vacuo.
13C NMR analysis of the residual catalyst from the H2-hydro-
genation reveals a distinct peak pattern for the three different
carbon sets in the cyclopentadienone ring and the metal-
bound carbonyls, which do not match with the signals found
for Ru-1, Ru-2, and Ru-3, or with the starting materials to syn-
thesize these catalyst precursors (Fig. 2). The disappearance of
the signal at 174 ppm and appearance of a signal at 108 ppm
may be an indicator for a change in the architecture of the
ligand (e.g. deoxygenation), rendering the deactivated material
to be a unique species. We also isolated the catalyst used after
the FA-mediated transfer hydrogenation for analysis, however,
in this case the successful reformation of Ru-2 was observed.
Considering these results, some plausible explanations for
the catalyst deactivation appear to rely on differences between
this work and the catalytic system of Fábos et al.22 Since our re-
cycling studies were performed at 120 °C instead of 100 °C,
while observing catalyst deactivation within 3 hours at 140 °C
(Fig. 1A), eventual deactivation at lower temperatures remains
a possibility after a longer time. On the other hand, in our
work H2 was used as reductant instead of FA. While associ-
ation of H2 to any of the Shvo catalyst precursors leads to the
sensitive Ru-4, association of FA to Ru-2 could potentially yield
a stable organometallic adduct in situ.
However, a vital clue was found in the work of Pasini et al.,
who applied the Shvo catalyst in the hydrogenation of HMF at
90 °C.36 Herein, recycling studies of Ru-2 from both toluene as
well as a biphasic water/toluene medium, and the introduction
of water was evidenced to be destructive for the catalyst. In
light of this information, we sought to eliminate water from LA
hydrogenation in this work, and replaced LA by ethyl levulinate
(EL), which co-produces ethanol instead of water. Strikingly,
the Shvo catalyst applied in this reaction could be reused
without losing activity after two recycles (Fig. 3). Moreover, the
kinetic curve of EL was found to be practically identical to that
of LA hydrogenation under the optimal conditions
(ESI, Fig. S2.2†). The use of EL instead of LA is therefore a
more preferable substrate for the synthesis of GVL by
H2-mediated hydrogenation using Shvo-type catalysts.
Evaluating the role of water in catalyst deactivation further,
this concept does not readily apply to the work of Fábos et al.22
However, their three successful catalyst recycles could rely on
experimental differences. We believe the use of FA as hydrogen
donor is the most likely cause, and possibly manifests via
more stabilization of the catalytic species and/or dilution of all
components in the reaction mixture.
2.4. Kinetic and thermodynamic comparison of hydrogen
donors by DFT calculations
Reflecting on the kinetic reaction profiles at different tempera-
tures in this work, a significantly lower activity is observed for
the H2-hydrogenation of LA at 100 °C in this work (Fig. 1A),
than for the FA-mediated hydrogenation at 100 °C (with Ru-2),
as described by Fábos et al.22 The maximal TOF’s for these are
144 h−1 and approximately 400 h−1, respectively. However,
upon increasing the temperature of the H2-hydrogenation this
Fig. 2 13C NMR spectra of the catalyst precursors, and the recycled
material derived from Ru-1.
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difference is annulled. In addition, the hydrogenation of LA
with H2 in this work proceeds relatively fast, compared to the
transfer hydrogenation with IPA (in toluene at 80 °C), which
we reported earlier.27
For a fair comparison, we repeated the solvent-free transfer
hydrogenations of LA to GVL catalyzed by 0.1% Ru-1 using 2.5
equivalents of FA and IPA, respectively, at 100 °C and 120 °C
(Fig. 4). To allow temperatures above the boiling point of IPA,
the reactions were performed in an autoclave under 2.5 bar of
N2 atmosphere. Since the reaction with FA releases stoichio-
metric amounts of CO2, a pressurized reaction was not con-
sidered feasible and only 100 °C was applied. Moreover, no
activation of Ru-1 with FA as hydrogen donor was observed,
hence Ru-2 was used instead. At 100 °C reaction rates were
observed in the order FA > H2 > IPA, rendering TOF’s of 498,
144, and 81 h−1 in the linear regions, respectively. Upon apply-
ing an increased temperature of 120 °C to the reactions with
Fig. 5 The two different conformations of the phenyl substituents of
Ru-1. Left structure is ‘mirror’; right structure is ‘propeller’.
For the hydrogen transfers mediated by the Shvo catalyst,
the mechanisms of Assary et al.41 and Casey et al.42 concerning
FA and alcohols, respectively, were assumed. The mechanism
for the splitting of H2 is also adapted from Casey et al. These
structural mechanisms are shown in Fig. 6–8 (vide infra), and
always feature a concerted hydrogen transfer, which has been
evidenced unanimously before.31,42,43
H2 and IPA the reaction rates increased to 598 and 257 h−1
respectively.
,
In order to elucidate these experimental outcomes, DFT cal-
culations were performed. Herein, the goal is to compare the
energetic hydrogenation pathways, facilitated by H2, IPA, and
FA, and to correlate the results with the experimental findings.
The computational structures were optimized using the hybrid
B3LYP function,37 and the LANL2DZ core potential38 was
applied on all atoms. Unlike some earlier reports,39 in this
work the Shvo catalyst was computed without any structural
simplification. Since Hollmann et al.40 identified two energetic
minima regarding the conformation of the four phenyl rings
(i.e. mirror and propeller; Fig. 5), we have taken both confor-
mations into account for these calculations. The energetic
difference between these two conformations varies from 0.0 to
2.1 kcal mol−1 throughout our calculated structures, as a result
of steric hindrance. However, conformational interchange is
considered possible at any stage of the catalytic mechanism.
In closer detail, the generic catalytic cycle can be accessed
by the formation of either Ru-4, Ru-5, or both, depending on
the used catalyst precursor. In Scheme 3, the catalytic cycle
starts with Ru-5 (I). From here, a hydrogen donor associates to
the catalyst (II), and the transition state is crossed via a con-
certed heterolytic hydrogen transfer (in case of FA and IPA as
hydrogen donors) (TS1). As such, a protonic and a hydridic
moiety are generated on the catalyst, while the residual part of
the hydrogen donor (if present) has become carbonylic (III),
and is then dissociated to form the active 18e− species Ru-4
(IV). Subsequently, LA associates onto Ru-4 in an outer-sphere
fashion (V). Next, another transition state is crossed (TS2),
corresponding to the concerted transfer of the proton and
hydride of Ru-4 to the ketone functionality of LA. Hence, the
catalyst is reverted into a 16e− species, while LA is converted
into 4-hydroxyvaleric acid (4-HVA) (VI). The catalytic cycle is
closed by the dissociation of 4-HVA (VII), however, 4-HVA
cyclizes spontaneously into GVL via the extrusion of water
(VIII).
Fig. 4 Catalytic conversion of LA to GVL using different H-donors and
temperatures. Conditions: 0.1% Ru-1 in LA (neat) under 50 bar H2; 0.1%
Ru-1 in a mixture of 1 equiv. LA in 2.5 equiv. IPA; 0.1% Ru-2 in a mixture
of 1 equiv. LA in 2.5 equiv. FA.
Scheme 3 Generic catalytic cycle for the Shvo-catalyzed hydrogen-
ation of LA to GVL.
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Fig. 6 Energetic reaction profile for the regeneration of the active Shvo catalyst species using FA, followed by the Shvo-catalyzed hydrogenation of
LA to GVL. The Gibbs free energy is normalized as such, that stage VII equals 0.0 kcal mol−1. A summary of the computational outputs is provided in
the ESI.†
Fig. 7 Energetic reaction profile for the regeneration of the active Shvo catalyst species using IPA, followed by the Shvo-catalyzed hydrogenation
of LA to GVL. The Gibbs free energy is normalized as such, that stage VII equals 0.0 kcal mol−1. A summary of the computational outputs is provided
in the ESI.†
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Fig. 8 Energetic reaction profile for the regeneration of the active Shvo catalyst species using H2, followed by the Shvo-catalyzed hydrogenation of
LA to GVL. The by-pass reaction pathway colored in blue depicts the energetic profile for the splitting of H2 co-catalyzed by a water molecule. The
Gibbs free energy is normalized as such, that stage VII equals 0.0 kcal mol−1. A summary of the computational outputs is provided in the ESI.†
The reaction with FA (Fig. 6) was firstly remodeled, since Ultimately, the dissociation of 4-HVA and its cyclization (step
only a simplified version of the Shvo catalyst was reported by TS2 – VIII) are calculated to be an all-exothermic pathway of
Assary et al., who substituted its phenyl groups with hydro- 9.2–10.2 kcal mol−1 to yield GVL. This result suggests that acti-
gens.41 It should be noted that, although our results are for vation of Ru-5 by FA (step I to IV) is practically a spontaneous
the larger part qualitatively the same, the presence of the process, and therefore the hydrogen transfer to LA (TS2) is the
phenyl groups has a significant influence on the Gibbs free rate-determining step. Moreover, the pathway from I to IV is
energy differentials, that are steric as well as electronic in unlikely to revert in case of FA, because the gaseous CO2 by-
nature.
product readily evaporates from the reaction mixture. However,
Our calculations reveal an energetically favorable associ- despite such favorable conditions, a minimal temperature of
ation of FA to Ru-5 (step I–II), followed by a practically non- 80 °C is still required, because at lower temperatures Ru-4
existent transition barrier (ΔGTS1 = 0.0–1.2 kcal mol−1) for the tends to dimerize into inactive Ru-2.
hydrogen transfer (TS1). The subsequent formation and dis-
The energetic reaction profile for the transfer hydrogen-
sociation of CO2 (step TS1 – IV) renders a combined exother- ation using IPA was also calculated as a reference to our experi-
mic value of 16.5–18.3 kcal mol−1. In the second part (step IV– mental work reported earlier (Fig. 7).27 Herein, the regener-
VIII), which is identical for all three reactions in terms of ΔG, ation of Ru-4 features a slightly endothermic association of
LA association to Ru-4 appears only slightly endothermic IPA to Ru-5 (step I–II), rendering 0.9–1.1 kcal mol−1. This is fol-
(ΔGTS2 = 0.4–1.8 kcal mol−1), while the hydrogen transfer to LA lowed by a transition barrier of 5.4–6.3 kcal mol−1 for the
features a transition barrier of 13.7–14.9 kcal mol−1 (TS2). hydrogen transfer (TS1). The subsequent extrusion of acetone
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renders an exothermic 14.4–15.0 kcal mol−1, which is quanti- After H2 association to Ru-5 (II), LA associates with its acidic
tatively comparable to the energetic barrier of TS2. As such, a proton to the cyclopentadienone ligand. Then, two modes of
rather symmetric energetic profile concerning step I–VII is concerted H2 splitting co-catalyzed by LA were considered: (a)
observed. This correlates with the Meerwein–Ponndorf–Verley One hydrogen from H2 migrates to the sp3-hybridized oxygen
equilibrium, however, the reaction is ultimately dragged to of LA, which simultaneously donates its own acidic proton to
completion by the exothermic cyclization of 4-HVA to GVL the cyclopentadienone ligand, followed by dissociation of levu-
(step VII–VIII).
linic acid forming Ru-4. This mode is nearly identical to the
Finally, to probe our present work into this thermodynamic ‘water-relay’ mechanism in terms of mechanistic atom inter-
context, the pathway in which H2 is heterolytically split by Ru-5 actions, as well as the energetic pathway, rendering a tran-
directly was first calculated (Fig. 8, black and purple plots). As sition barrier of 5.4–6.8 kcal mol−1 (ESI, Fig. S4.1†). Hence,
such, the catalyst regeneration is initiated by an endothermic this interaction could possibly co-exist with the ‘water-relay’
association of H2 onto the ruthenium atom of Ru-5, rendering mechanism in the reaction, but providing spectroscopic dis-
3.8–4.4 kcal mol−1 (I–II). Then, via transfer of one hydrogen tinction between these mechanisms is deemed impossible due
atom to the cyclopentadienone ligand, the transition state for to proton-scrambling. (b) The other investigated mode con-
hydrogen splitting is engaged (TS1, black and purple plots), cerns a relay mechanism involving both carboxylic oxygen
which leads directly to the formation of Ru-4 without the for- atoms. One hydrogen from H2 migrates to the sp2-hybridized
mation of by-products (IV). This process consumes a remark- oxygen of LA, which transfers its electron density via the car-
ably high 28.1–29.4 kcal mol−1 for TS1, but releases a see- boxylic carbon to the sp3-hybridized oxygen, and simul-
mingly irreversible 43.6–45.5 kcal mol−1 for step TS1 – IV. taneously donating the acidic proton to the cyclopentadienone
Hence, the rate-determining step in this scenario appears to ligand as such, which is most resembling to related inter-
be the splitting of H2 instead of hydrogen transfer to LA, actions by phosphoric acids.34b–e,44,45 This mode of LA associ-
unlike the cases for the reactions with FA and IPA.
ation to the Shvo catalyst and H2, as well as the resting state
Although certain values of about 29 kcal mol−1 were after hydrogen splitting are found more exergonic than the
reported to be viable for H2 splitting by structurally related previously described interaction with LA. However, the found
iron Knölker-type catalysts,43 this computational outcome does transition state for the anticipated concerted hydrogen-transfer
not correlate with our experimental findings. Therefore we also mechanism reveals a negative ΔG, and the corresponding
considered an alternative reaction pathway featuring a ‘water- molecular vibration is only visible for the splitting of H2, but
relay’ mechanism (Fig. 8, blue plot), which is evidenced via not for the transfer of the proton from LA to the cyclopentadie-
deuterium labelling studies by Casey et al.42a According to this none ligand (ESI, Fig. S4.2†). This mismatch suggests that the
mechanism, after H2 association to Ru-5 (II), a water molecule proposed concerted mechanism in this particular mode may
associates onto the cyclopentadienone ligand (II*). A transition not be existent.
barrier of only 5.8–6.7 kcal mol−1 is then observed for the
Thus, based on our DFT studies, viable reaction pathways
water-mediated hydrogen transfer, in which one hydrogen for the Shvo-catalyzed (transfer) hydrogenation of LA to GVL
atom from H2 is donated to the oxygen atom of the water, using FA, IPA, H2 + H2O, and one interaction mode for H2 + LA
while the water molecule passes one of its own hydrogens to as hydrogen donors were calculated. For each of the four
the cyclopentadienone ligand in a concerted way (TS1). The hydrogen donor combinations the hydrogen transfer to LA
following completion of the hydrogen transfer and dis- (TS2) is predicted to be the rate-determining step. On the
sociation of water (step TS1 – IV) yield Ru-4 as well. Since the other hand, the thermodynamic gain for the catalyst activation
transition barrier for water-catalyzed H2 splitting is notably by the hydrogen donor – and therefore for the entire reaction –
lower compared to that of the ‘dry’ mechanism, and the hydro- is in the order: FA > H2 + H2O = H2 + LA > IPA. Since the mag-
genation of LA to GVL co-produces water, we regard only the nitude of ΔG co-defines the reaction equilibrium as eqn (1), it
‘water-relay’ mechanism as representable for our study. also controls the reaction rate by establishing the equilibria
Importantly, the co-catalysis by water causes the energetic throughout step I–VIII. Therefore, the order of ΔG for FA, IPA,
barrier of TS1 to become lower than that of TS2, hence turning H2 + H2O, and H2 + LA is qualitatively in accordance with the
TS2 into the rate-determining step.
observed reaction rates for the corresponding hydrogen donors
Alternatively, H2 splitting aided by the carboxylic acid func- at equithermal conditions.
tionality of LA is another potential mechanism that could take
ΔG
½GVLꢀ½H2Oꢀ½byproductꢀ
K ¼
¼ eꢁ
ð1Þ
place in this particular reaction. Although no experimental evi-
dence for H2 splitting by Shvo-type catalysts employing car-
boxylic acids as co-catalysts is available in literature yet,
examples of hydrogen-shuttling induced by phosphoric acids
are known,44 of which some also involve the related Knölker
RT
½LAꢀ½H‐donorꢀ
2.5. Life cycle assessment
catalyst.34b–e,45 Based on the interactions described in these With the complete, optimized experimental data, and a
reports and the ‘water-relay’ mechanism by Casey et al.,42a we rational overview of thermodynamic feasibility for all Shvo-
considered similar concerted mechanisms, in which classical catalyzed (transfer) hydrogenations of LA to GVL at hand, it is
hybridization of the acidic oxygen atoms of LA was assumed. interesting to identify the most desirable methodology with
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respect to green chemistry practices. A quantitative expression hydrogenation reactions were performed on laboratory scale,
in terms of environmental impact can be derived from a LCA rendering 20–43 g of GVL product. However, to apply a
as an accurate indicator or comparative value for such.
uniform comparison on representative scale, the functional
LCA is an analytical tool, that is standardized in the ISO unit (FU) was chosen as 10 g of GVL, being in accordance with
14040 series,46 to assess the environmental impact of a the product category rules (PCR) of the environmental product
product or service. Herein, the combined total of all material declaration (EPD).53
inputs and outputs, energy consumption, and other process
As shown in Scheme 4, the procedure for converting LA to
attributes (e.g. workup procedures, transport, waste manage- GVL is initiated by creating an inert atmosphere for the reac-
ment) are preferably included as complete as possible for an tion by purging with nitrogen (and optionally H2, in case of
accurate assessment.47
direct hydrogenation). The purged gas is released from the
In recent years, numerous LCAs in the field of chemistry system, thus regarded as waste. In the next step, the (transfer)
have appeared, with the focus on evidencing the benefit of hydrogenation reaction takes place, for which any of the Shvo-
applying bio-based feedstock,48 alternative synthesis routes,49 type catalyst precursors, any of the three different hydrogen
and innovative procedures.50 However, many of these novel donors, and electric energy are the input. The environmental
researches are merely conducted in early-development stages, impact of LA is not taken into account here, since this LCA is a
such as laboratory scale or computational process simulations. ‘gate-to-gate’ assessment. Depending on the scenario, residual
Hence, their corresponding LCA’s are prospective, with the nitrogen or H2, or CO2 by-product are considered as waste. The
purpose of, for example, identifying the key aspects towards GVL product is isolated via the DSP steps, which consume elec-
improvement in upscaling,51 or to compare the benefit of tric energy for heating and cooling water circulation. First, a
choosing a raw material from a selection.48a,52
mild vacuum distillation is applied to remove water, and any
In this work, we performed a prospective LCA comprising a residual liquid hydrogen donor (i.e. FA, IPA), and acetone by-
comparison of several reaction parameters for the Shvo-cata- product if present. In the harsh vacuum distillation, pure GVL
lyzed (transfer) hydrogenation of LA to GVL, in terms of is distilled from the catalyst. The spent catalyst is discarded in
environmental impact. These parameters concern the catalyst the main scenario, however, catalyst recovery from the distilla-
precursor, hydrogen donor, temperature, and time of the reac- tion residue and recycling is considered in the sensitivity ana-
tion, aiming for the optimal balance between environmental lysis (vide infra).
impact and process metrics. The included reactions are
described in section 2.4 (Scheme 4), and the function studied rosynthesis was devised on the basis of standard laboratory
in this LCA is the production and isolation of GVL.
scale reports found in literature (Scheme 4).54–62 Firstly, these
For the assessment of Ru-1, Ru-2, and Ru-3, a plausible ret-
The life cycle inventory (LCI) comprises three different Shvo-type catalyst precursors are conventionally synthesized
hydrogenation methods, which are [1] transfer hydrogenation from tetraphenyl-cyclopentadienone and triruthenium dodeca-
using FA and emitting CO2, [2] transfer hydrogenation using carbonyl, as shown in Scheme 2. Although various procedures
IPA and co-producing acetone, and [3] direct hydrogenation for synthesis and purification with different isolated yields
using H2 without generating any by-product. Herein, the exist in literature,22,29,57,64,65 those acquired from the present
boundaries of this LCA are chosen to be ‘gate-to-gate’ for the work are adopted as the base case in this LCA. Furthermore,
production and isolation of GVL from LA (Scheme 4). This the ligand is produced via the double aldol condensation of
means that the environmental impact of consumed chemicals, benzil and diphenyl ketone,57 which are ultimately derived
electric energy input, and downstream processing (DSP) are from benzaldehyde and benzyl chloride, respectively. The trir-
taken into account for this chemical transformation, but not uthenium dodecacarbonyl is ultimately produced from metal-
for the synthesis of LA from primary resources. Excluding the lic ruthenium,55,56 which is a by-product from platinum ore
environmental impact of LA synthesis can only provide reliable mining, purification, and refining processes.56
comparisons, if the assessed LA hydrogenations achieve 100%
The total procedure for the (transfer) hydrogenation reac-
conversion to GVL with complete isolation. We consider it tions, product isolation, and the catalyst synthesis routes were
reasonable to assume this for the present work, given that all modelled in Simapro V8 (PRé consultants, NL). The environ-
the actual LA conversions equal at least 97%. The choice for mental impacts were calculated using the IMPACT 2002+
this boundary was made, because the only reported LCA on LA V2.14 method, and the results are generally expressed as
production to our knowledge is based on a process model and damage categories.66 However, mid-point categories were used
is too specific with respect to a location or feedstock,47b and is for the life cycle impact assessment interpretations. The
therefore not representative for this work. Moreover, as GVL climate change impact was calculated with the IPCC GWP
provides a very wide versatility in further applications and pro- 100a mid-point method, in accordance with the updated
ducts, its ‘end-of-life’ scenario is regarded as yet undefined in method from the Intergovernmental Panel on Climate Change
this work. The applied Shvo catalyst precursors were modelled (IPCC).67
as ‘cradle-to-gate’ (vide infra), to demonstrate the environ-
The potential environmental impacts of the five different
hydrogenation scenarios, were investigated on four different
mental impact for their synthesis and use in this reaction.4
The present LCA is modelled in accordance with the experi- end-point categories, and scaled with respect to the functional
mental execution described in sections 2.2, 2.3, and 2.4. All unit:
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Scheme 4 The studied boundaries and process flow-sheet for the production of GVL from LA on laboratory scale: comparative gate-to-gate
assessment including [1] the transfer hydrogenation of the substrate using FA as reductant, [2] the transfer hydrogenation of the substrate using IPA
as reductant, [3] the hydrogenation of the substrate using H2, and [4] the syntheses of the Shvo catalyst precursors. Reaction conditions: (a)
Metalation (in toluene, N2, 110 °C, 24 h, 98%); (b) metalation (in MeOH, N2, 65 °C, 24 h, 51%); (c) metalation (in heptane, N2, 100 °C, 48 h, 58%); (d)
carbonylation (ethoxyethanol, CO, KOH, 75–135 °C, 145 min, 96%);54 (e) chlorination (neat, Cl2, 360–390 °C, 8 h, 100%);55 (f) mining/purification/
refining;56 (g) aldol condensation (in EtOH, Microwave, 70 °C, 30 min, 78%);57 (h) oxidation (in H2O/AcOH, NH4NO3, 1% Cu(II)OAc2, 100 °C, 2.5 h,
94%);58 (i) Benzoin condensation (in DMSO, Ar, NaCN, Ultrasound, 25 °C, 10 min, 98%);59 ( j) Dakin-West reaction (neat, N2, Ac2O, Et3N, 25 °C, 48 h,
69%);60 (k) hydrolysis (in H2O/H2SO4, 100 °C, 3 h, 78%);61 (l) Kolbe nitrile synthesis (in H2O, NaCN, 80 °C, 4 h, 85%).62 Reactions a–c are conducted
in this work, reactions d–l are adapted from literature procedures. Additional chemicals (i.e. ethoxyethanol for reaction d, copper sulfate for reaction
h, and triethylamine for reaction j), required in these syntheses, of which the impact could not be derived from the database, were assessed on the
basis of literature procedures as well.63 Electricity consumptions are denoted as “E” (see ESI Table S5.1† for details). Dashed arrows indicate an
optional reaction- or DSP-pathway.
(1) Damage to human health, expressed in disability- emission type is scaled to kg CO2 equivalents, in accordance
adjusted life year (DALY). This includes human toxicity, respir- with the global warming potential (GWP) as conversion factor,
atory effects, ionizing radiation, ozone-layer depletion, and provided by the IPCC.67
photochemical oxidation.
(4) Resources, expressed in MJ, are calculated by the sum of
(2) Ecosystem quality, expressed in potentially disappeared energy derived from non-renewable feedstock and mineral
fraction of species per m2 per year (PDF m−2 year−1). Herein, extractions.
aspects for both aquatic and terrestrial ecotoxicity (e.g. acidifi-
cation, eutrophication, land occupation) are taken into contributions of process features to the damage categories are
account. presented in Fig. 9. Remarkably, the largest contributors to
For the optimized H2-hydrogenation at 120 °C, the relative
(3) Climate change, as a result from greenhouse gas emis- nearly the entire environmental impact are the electric energy
sions into the environment. The severity of the impact per consumption required for the hydrogenation reaction and the
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Fig. 10 Reduction of the environmental impact of the catalyst by
improving its isolated yield. The catalyst synthesis concerns Ru-1, but for
the FA-mediated reaction Ru-2 is modelled.
Fig. 9 Magnitude of contribution to four environmental impact cat-
egories for the optimized hydrogenation reaction in this work. The total
values for each impact category are indicated below the x axis.
catalyst synthesis. This is also found for the other reaction
scenarios (ESI S5.1†), but their impact distribution slightly
differs. Herein, a trend between the electric energy impact and
the reaction duration is clearly visible. However, the lowest
electric impact found for the FA-mediated reaction can be
rationalized by having the reaction performed in a reflux
setup, instead of using an autoclave. Despite the small numeri-
cal difference, the impact of H2 consumption appears notably
lower than that of FA or IPA. Since the four damage categories
always indicate a similar impact distribution, only the GWP
was selected for further investigations.
The catalyst synthesis delivers a large part of the impact to
this reaction process, while its loading counts only 0.1 mol%
with respect to LA. Therefore, it is considered worthy to identify
the cause of this result, and how to improve it. First, the GWP’s
of the hydrogenation reactions were modelled as a function of Fig. 11 Sensitivity analysis of the catalyst syntheses in relation to the
GWP of the hydrogenation reactions.
the isolated catalyst yields (Fig. 10). The curves indicate signifi-
cant reductions of the GWP in all hydrogenation scenarios,
however, the relatively highest reductions are seen for the FA-
and H2-mediated reactions. The yield of Ru-1 in this work is mental impact of LA hydrogenation in terms of H-donors is in
already an excellent 98%. Contrarily, improving our isolated the order: IPA > FA > H2 (Fig. 11). To eliminate the difference in
yield of 51% for Ru-2 could reduce the GWP of the corres- GWP caused by significantly different isolated yields amongst
ponding FA-mediated hydrogenation reaction up to 27%.
Ru-1 and Ru-2, but not neglecting the incompatibility of Ru-1
It should be mentioned though, that the GWP of the cata- with FA, a combinatorial comparison was devised between the
lyst is strongly dependent of the applied synthetic procedure optimal reaction conditions for using each H-donor, and apply-
as well as the DSP methodology, and isolated yield. ing each Shvo catalyst precursor with a modelled 98% isolated
Throughout various literature procedures for synthesizing yield (ESI S5.3†). Also in this hypothetical circumstance the use
Ru-1,64 Ru-2,22,29,57 and Ru-365 the electricity consumption of H2 as H-donor shows the lowest GWP.
originating from the reaction duration and the solvent amount
The environmental impact of the FA-mediated reaction
used for column chromatography are found to be the most could arguably be reduced in two ways. Since FA is a concomi-
dominant impact factors (ESI, Fig. S5.2†). The variation in tant by-product from the hydrolysis of HMF to LA (Scheme 1),
these aspects significantly affects the total GWP of the LA 1 equivalent of FA can be bio-derived from the same feedstock.
hydrogenation reactions (Fig. 11).
As such, the environmental impact for the separation of LA
Nevertheless, by considering the isolated yields of Ru-1 and from FA could then be eliminated, however, this separation
Ru-2 obtained in this work, the magnitude of the environ- step is not included within the gate-to-gate boundaries of this
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LCA. Secondly, Fábos et al. have demonstrated the use of only
0.5 equivalents of excess FA to be feasible for 99.9% conver-
sion,22 while 1.5 excessive equivalents were used in this work.
Hence, the effects of these two potential eliminations of petro-
chemical formic acid were assessed in our catalytic system, but
even the combination of these effects inflict only a lean 2%
reduction of the GWP (ESI S5.4†).
To furtherly decrease the impact of the catalyst synthesis,
the benefit of potential recycling was assessed. Although we
concluded that recycling of the Shvo catalyst is incompatible
with LA because of deactivation by co-produced water (section
2.3, Fig. 3), it is still interesting to investigate its hypothetical
recycling as a model for the EL hydrogenation or even other
reactions outside this work. The corresponding calculation can
be described by dividing the GWP accounting for the catalyst
synthesis by the number of each following hydrogenation
cycle, but not for the DSP, as this recurs in each cycle. The
obtained plot (ESI, Fig. 5.5†) reveals a decreasing decline after
each recycle, leading to a reduction from 44% to less than 7%
of the total GWP for the hydrogenation reaction after ten
recycles, compared to a reaction without catalyst recycling.
Beyond this point an asymptote is reached, whereas 147
recycles are required to draw the catalyst’s impact below 1%.
We consider a minimum of ten recycles without losing cata-
lytic activity a proper goal to thrive for.
In addition, a further decrease of the environmental impact
could be envisioned by immobilizing the catalyst. Supported
Shvo-type complexes are known,68 and their application would
allow facile catalyst separation by filtration. As such, the harsh
distillation step in the DSP can be omitted, which reduces the
environmental impact by 31%. However, it is important to
mention that immobilizing the Shvo catalyst requires extra syn-
thesis steps, which increases the impact of the catalyst syn-
thesis in turn, and catalyst decomposition by sensitivity to
water may still occur. In addition, the GVL product is likely to
be of lower purity, because in this scenario GVL is collected
from the mild distillation residue.
Fig. 12 Expansion of GWP (kg CO2 equivalents per 10 g of product) as
a function of reaction time and the isolated yield for Ru-1. The optimal
reaction established in this work (i.e. 120 °C, 50 bar H2) is selected. The
crosshair indicates the current isolated yield and reaction time.
case LA hydrogenation in this work (Fig. 12). In this way, an
environmentally optimal combination of the reaction parameter
values can be pinpointed, in order to achieve the lowest impact
possible. In the case of the present reaction, the isolated yield
for Ru-1 (98%) can hardly be improved. However, by shortening
the reaction time from 5 hours to 3 hours, an appreciable
decrease of 0.5 kg CO2 eq. per 10 g GVL, corresponding to 7%,
can be achieved. LCA representations of this kind can make a
useful tool to predict the optimal reaction metrics for develop-
ing chemical reactions on laboratory scale into large-scale pro-
cesses, in the context of green chemistry practices.
3. Conclusions
Finally, the duration of the hydrogenation reaction is
regarded as the other vital parameter in terms of environ- This multi-disciplinary study describes the selective hydrogen-
mental impact, whereas it is directly proportional to the reac- ation of LA to GVL under solvent-free conditions using the
tion’s electricity consumption. While the applied reaction Shvo catalyst. In this specific reaction, the use of hydrogen gas
temperature is one significant factor, also the choice of as reducing agent is the novelty, for which the effects of
H-donor plays a dominant role, resulting from the differences various reaction conditions were thoroughly investigated by
in thermodynamic properties amongst the three reaction path- means of kinetic studies using the monomeric Shvo-type cata-
ways, as demonstrated by the DFT studies in section 2.4. Based lyst Ru-1. The optimal laboratory scale protocol to yield 99.7%
on the kinetic reaction curve in Fig. 1D, a minimum in conversion within 5 hours is achieved by heating at 120 °C
environmental impact could potentially be realised by mitigat- under 50 bar H2, using 0.1 mol% [Ru], and this applies to each
ing between a shorter reaction time and slightly lower GVL of the possible Shvo catalyst precursors known.
yield. For the LA hydrogenation catalyzed by Ru-1 it is possible
Attempts to recycle the catalyst from the LA hydrogenation
to shorten the reaction time for at least 1 hour, while being were not successful, since the co-produced water appears to de-
reacted at 120 °C under 50 bar H2. However, applying a reac- activate the catalyst. However, successful catalyst recycling can
tion time under 2 hours goes severely at the cost of the GVL be achieved by substituting LA for EL, which renders an identi-
yield, and is therefore deemed not feasible. To illustrate this in cal kinetic plot in the same hydrogenation reaction, but co-pro-
a numerical fashion, the GWP was plotted as a function of the duces ethanol instead of water.
reaction time and the isolated yield for Ru-1, which are the two
The comparison of H2 versus other hydrogen donors – FA
largest contributors to the environmental impact of the base and IPA – under similar solvent-free conditions result in sig-
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nificantly different reaction rates, in the order of FA > H2
>
References
IPA. Computational modelling of each reaction using DFT
indicate the energetic transition barrier for hydrogen splitting/
transfer generating the active catalytic species, and also the
overall exothermic energy loss to be the determining factors in
these reaction rates. In addition, the role of water in co-catalyz-
ing H2 splitting via a relay mechanism was considered as a
more plausible reaction pathway than direct H2 splitting,
based on the magnitude of their energetic transition barriers.
As such, the interpretation of the DFT study correlates properly
with the experimental observations.
To identify the optimal hydrogen donor from an environ-
mental perspective, the LA hydrogenation procedures featuring
the three different hydrogen donors were subjected to a com-
parative gate-to-gate LCA. Herein, the environmental impacts of
the Shvo catalyst precursors are modelled as a cradle-to-gate
LCA, mostly based on secondary literature-derived information.
The results reveal for all (transfer) hydrogenation reactions, that
the total electricity consumption and the catalyst synthesis are
the main contributors to the environmental impact with a com-
bined part of ≥95%. Sensitivity analysis of these factors shows
that a significant variation in the GWP is possible, depending
on the reaction duration/temperature/thermodynamics, and
synthetic procedure, respectively. Therefore, effectively decreas-
ing the environmental impact could be established by balancing
out the reaction time versus the GVL yield, and to apply catalyst
recycling (if possible) for at least 10 times.
However, in the optimistic-realistic scenario, where all reac-
tions are assumed to achieve 100% conversion within their
applied optimal reaction conditions, and all catalyst precursor
yields are normalized to 98%, the magnitude of environmental
impact renders IPA ≫ FA > H2. Hence, the present LCA demon-
strates the use of H2 to be the ‘greenest’ choice, originating
from the short reaction time compared to the reaction with
IPA, and to the absence of the stoichiometric CO2 by-product
compared to the reaction with FA. We expect the environ-
mental benefit of using H2 to be more pronounced in scaled-
up facilities, which generally display a much higher energy
efficiency than laboratory-scale equipment.
With this research, we would also like to emphasize the value
of combining different research interests and methodologies in
today’s chemistry, whereas the interfaces between them may
create a pivotal synergy in understanding the chemistry, and
therefore how to achieve the greenest and most efficient process.
1 (a) G. W. Huber, S. Iborra and A. Corma, Chem. Rev., 2006,
106, 4044; (b) A. Corma, S. Iborra and A. Velty, Chem. Rev.,
2007, 107, 2411; (c) J. J. Bozell and G. R. Petersen, Green
Chem., 2010, 12, 539.
2 (a) R. C. Saxena, D. K. Adhikari and H. B. Goyal, Renewable
Sustainable Energy Rev., 2009, 13, 167; (b) P. Mäki-Arvela,
B. Holmbom, T. Salmi and D. Y. Murzin, Catal. Rev., 2007,
49, 197; (c) G. Centi, P. Lanzafame and S. Perathoner, Catal.
Today, 2011, 167, 14; (d) R. Serrano-Ruiz, A. Luque and
A. Sepulveda-Escribano, Chem. Soc. Rev., 2011, 40, 5266.
3 (a) K. H. Kim, M. Tucker and Q. Nguyen, Bioresour.
Technol., 2005, 96, 1249–1255; (b) A. Fukuoka and
P. L. Dhepe, Angew. Chem., Int. Ed., 2006, 45, 5161–5163;
(c) P. Lenihan, A. Orozco, E. O’Neill, M. N. M. Ahmad,
D. W. Rooney and G. M. Walker, Chem. Eng. J., 2010, 156,
395–403; (d) D. M. Alonso, J. Q. Bond and A. Dumesic,
Green Chem., 2010, 12, 1493–1513.
4 T. Werpy, G. Petersen, A. Aden, J. Bozell, J. Holladay,
J. White and A. Manheim, in Top Value Added Chemicals
from Biomass: Volume 1 – Results of Screening for Potential
Candidates from Sugars and Synthesis Gas, ed. T. Werpy and
G. Petersen, U. S. Department of Energy, Washington, DC,
2004.
5 (a) L. Qi, Y. F. Mui, S. W. Lo, M. Y. Lui, G. R. Akien and
I. T. Horváth, Chem. Commun., 2012, 48, 5850; (b) L. Yan,
Q. Yao and Y. Fu, Green Chem., 2017, 19, 5527.
6 (a) I. T. Horváth, Green Chem., 2008, 10, 1024;
(b) J. Q. Bond, D. Wang, D. M. Alonso and J. A. Dumesic,
J. Catal., 2011, 281, 290; (c) J. Q. Bond, D. M. Alonso,
D. Wang, R. M. West and J. A. Dumesic, Science, 2010, 327,
1110; (d) D. Fegyverneki, L. Orhá, G. Láng and
I. T. Horváth, Tetrahedron, 2010, 66, 1078; (e) A. Strádi,
M. Molnár, M. Óvári, G. Dibó, F. U. Richter and L. T. Mika,
Green Chem., 2013, 15(7), 1857; (f) L. Qi, Y. F. Mui,
S. W. Lo, M. Y. Liu, G. R. Akien and I. T. Horváth, ACS
Catal., 2015, 4, 1470.
7 V. Fábos, M. Y. Lui, Y. F. Mui, Y. Y. Wong, L. T. Mika, L. Qi,
E. Cséfalvay, V. Kovács, T. Szucs and I. T. Horváth, ACS
Sustainable Chem. Eng., 2015, 3, 1899.
8 J.-P. Lange, R. Price, P. M. Ayoub, J. Louis, L. Petrus,
L. Clarke and H. Gosselink, Angew. Chem., Int. Ed., 2010,
49, 4479.
9 (a) C. W. Lee, R. Urakawa and Y. Kimura, Eur. Polym. J.,
1998, 34, 117; (b) M. Chalid, H. J. Heeres and
A. A. Broekhuis, J. Appl. Polym. Sci., 2012, 123, 3556;
(c) M. Chalid, H. J. Heeres and A. A. Broekhuis, Polym.-
Plast. Technol. Eng., 2015, 54, 234.
Conflicts of interest
The authors state that there are no conflicts to declare.
10 J. G. de Vries, Top. Catal., 2014, 57, 1306.
11 Good Scents Company, Parfumery Raw Materials
Information Sheet, http://www.thegoodscentscompany.
com/data/rw1024031.html.
Acknowledgements
This work was performed within the framework of the public- 12 (a) I. T. Horváth, H. Mehdi, V. Fábos, L. Boda and
private knowledge institute of Chemelot InSciTe, who we grate-
fully acknowledge for their financial support.
L. T. Mika, Green Chem., 2008, 10, 238–242;
(b) C. Y. Y. Wong, A. W-T. Choi, M. Y. Lui, B. Fridrich,
Green Chem.
This journal is © The Royal Society of Chemistry 2019

View Article Online
Green Chemistry
Paper
A. K. Horváth, L. T. Mika and I. T. Horváth, Struct. Chem.,
2017, 28, 423.
(c) S. Fleischer, S. Werkmeister, S. Zhou, K. Junge and
M. Beller, Chem. – Eur. J., 2012, 18, 9005; (d) S. Fleischer,
S. Zhou, S. Werkmeister, K. Junge and M. Beller, Chem. –
Eur. J., 2013, 19, 4997; (e) S. Zhou, S. Fleischer, H. Jiao,
K. Junge and M. Beller, Adv. Synth. Catal., 2014, 356, 3451;
(f) K. Natte, W. Li, S. Zhou, H. Neumann and X. F. Wu,
Tetrahedron Lett., 2015, 56, 1118.
13 (a) A. K. Ghosh and L. J. Swanson, Org. Chem., 2003, 68,
9823; (b) E. L. Stangeland and T. J. Sammakia, Org. Chem.,
2004, 69, 2381; (c) R. Datrika, S. R. Kallam, S. R. Khobare,
V. S. Gajare, M. Kommi, H. R. Mohan, V. Siddaiah and
T. Pratap, Tetrahedron: Asymmetry, 2016, 27, 603.
14 (a) W. H. R. Wright and R. Palkovits, ChemSusChem, 2012, 35 (a) S. A. Moyer and T. W. Funk, Tetrahedron Lett., 2010, 51,
5, 1657; (b) U. Omoruyi, S. Page, J. Hallett and P. W. Miller,
ChemSusChem, 2016, 9, 2037.
15 (a) J. M. Tukacs, M. Novák, G. Dibó and L. T. Mika, Catal.
Sci. Technol., 2014, 4, 2908; (b) A. Dutta Chowdhury,
R. Jackstell and M. Beller, ChemCatChem, 2014, 6, 3630.
16 (a) W. Li, J. Xie, H. Li and Q. Zhou, Green Chem., 2012, 14,
5430; (b) A. Pagnoux-Ozherelyeva, N. Pannetier,
M. D. Mbaye, S. Gaillard and J.-L. Renaud, Angew. Chem.,
Int. Ed., 2012, 51, 4976; (c) D. S. Merel, M. Elie, J. F. Lohier,
S. Gaillard and J.-L. Renaud, ChemCatChem, 2013, 5, 2939;
(d) B. Emayavaramban, M. Roy and B. Sundararaju, Chem. –
Eur. J., 2016, 22, 3952.
2388; (b) J. Deng, Y. Wang, T. Pan, Q. Xu, Q. Guo and Y. Fu, 36 T. Pasini, G. Solinas, V. Zanotti, S. Albonetti, F. Cavani,
ChemSusChem, 2013, 6, 1163; (c) S. Wang, H. Huang,
V. Dorcet, T. Roisnel, C. Bruneau and C. Fischmeister,
Organometallics, 2017, 36, 3152.
A. Vaccari, A. Mazzanti, S. Ranieri and R. Mazzoni, Dalton
Trans., 2014, 43, 10224–10234.
37 (a) P. J. Stevens, F. J. Devlin, C. F. Chablowski and
M. J. Frisch, J. Phys. Chem., 1994, 98, 11623; (b) A. D. Becke,
J. Chem. Phys., 1993, 98, 5648.
17 Y. Yi, H. Liu, L.-P. Xiao, B. Wang and G. Song,
ChemSusChem, 2018, 11, 1474.
18 H. Mehdi, V. Fábos, R. Tuba, A. Bodor, L. T. Mika and 38 (a) P. J. Hay and W. R. Wadt, J. Chem. Phys., 1985, 82, 299;
I. T. Horváth, Top. Catal., 2008, 48, 49.
19 F. M. A. Geilen, B. Engendahl, A. Harwardt, W. Marquardt,
J. Klankermayer and W. Leitner, Angew. Chem., Int. Ed.,
2010, 49, 5510.
20 J. M. Tukacs, D. Király, A. Strádi, G. Novodarszki, Z. Eke,
G. Dibó, T. Kégl and L. T. Mika, Green Chem., 2012, 14,
2057.
(b) S. Huizinga, J. Anzelm, M. Klobukowski, E. Radzio-
Andzelm, Y. Sakai and H. Tatewaki, Gaussian Basis Sets for
Molecular Calculations, Elsevier, Amsterdam, 1984.
39 (a) A. Comas-Vives, G. Ujaque and A. Lledós, Organometallics,
2007, 26, 4135; (b) A. Comas-Vives, G. Ujaque and A. Lledós,
J. Mol. Struct.: THEOCHEM, 2009, 307, 123.
40 D. Hollmann, H. Jiao, A. Spannenberg, S. Bähn, A. Tillack,
R. Parton, R. Altink and M. Beller, Organometallics, 2009,
28, 473.
21 L. Deng, J. Li, D. M. Lai, Y. Fu and Q.-X. Guo, Angew.
Chem., Int. Ed., 2009, 48, 6529.
22 V. Fábos, L. T. Mika and I. T. Horvath, Organometallics, 41 R. S. Assary and L. A. Curtiss, Chem. Phys. Lett., 2012, 541,
2014, 33, 181. 21.
23 S. Wang, V. Dorcet, T. Roisnel, C. Bruneau and 42 (a) C. P. Casey and J. B. Johnson, Can. J. Chem., 2005, 83,
C. Fischmeister, Organometallics, 2016, 36, 708.
24 G. Amenuvor, B. C. E. Makhubela and J. Darkwa, ACS
Sustainable Chem. Eng., 2016, 4, 6010.
1339; (b) C. P. Casey and J. B. Johnson, J. Am. Chem. Soc.,
2005, 127, 1883; (c) C. P. Casey, J. B. Johnson, S. W. Singer
and Q. Cui, J. Am. Chem. Soc., 2004, 127, 3100.
25 N. K. Oklu and B. C. E. Makhubela, Inorg. Chim. Acta, 2018, 43 (a) S. Moulin, H. Dentel, A. Pagnoux-Ozherelyeva,
482, 460.
S. Gaillard, A. Poater, L. Cavallo, J.-F. Lohier and
J.-L. Renaud, Chem. – Eur. J., 2013, 19, 17881; (b) T.-T. Thai,
D. S. Mérel, A. Poater, S. Gaillard and J.-L. Renaud, Chem. –
Eur. J., 2015, 21, 7066.
26 G. Amenuvor, J. Darkwa and B. C. E. Makhubela, Catal. Sci.
Technol., 2018, 8, 2370.
27 C. A. M. R. van Slagmaat and S. M. A. De Wildeman,
Eur. J. Inorg. Chem., 2018, 6, 694.
28 H. M. Jung, S. T. Shin, Y. H. Kim, M.-J. Kim and J. Park,
Organometallics, 2001, 20, 3370.
44 (a) B. Xu, S.-F. Zhu, Z.-C. Zhang, Z.-X. Yu, Y. Ma and
Q.-L. Zhou, Chem. Sci., 2014, 5, 1442; (b) Y.-Y. Ren, S.-F. Zhu
and Q.-L. Zhou, Org. Biomol. Chem., 2018, 16, 3087.
29 B. L. Conley, M. K. Pennington-Boggio, E. Boz and 45 K. Hopmann, Chem. – Eur. J., 2015, 21, 10020.
T. J. Williams, Chem. Rev., 2010, 110, 19.
30 C. P. Casey and H. Guan, Organometallics, 2012, 31, 2631.
31 C. P. Casey, S. Singer, D. R. Powell, R. K. Hayashi and
M. Kavana, J. Am. Chem. Soc., 2001, 123, 1090 (ref. 54.
32 Y. Shvo and D. Czarkie, J. Organomet. Chem., 1986, 315,
C25.
46 ISO 14044: 2006, Environmental Management – Life Cycle
Assessment – Requirements and Guidelines, International
Organization for Standardization, 2006.
47 (a) D. Kralisch, D. Ott and D. Gericke, Green Chem., 2015,
17, 123; (b) V. Isoni, D. Kumbang, P. N. Sharratt and
H. H. Khoo, J. Environ. Manage., 2018, 214, 267.
33 M. K. Thorson, K. L. Klinkel, J. Wang and T. J. Williams, 48 (a) H. H. Khoo, W. L. Ee and V. Isoni, Green Chem., 2016,
Eur. J. Inorg. Chem., 2009, 2, 295.
18, 1912; (b) R. Mazzoni, C. Cesari, V. Zanotti, C. Lucarelli,
T. Tabanelli, F. Puzzo, F. Passarini, E. Neri, G. Marani,
R. Prati, F. Viganò, A. Conversano and F. Cavani, ACS
Sustainable Chem. Eng., 2019, 7, 224.
34 (a) A. Tlili, J. Schranck, H. Neumann and M. Beller, Chem.
– Eur. J., 2012, 18, 15935; (b) S. Zhou, S. Fleischer, K. Junge
and M. Beller, Angew. Chem., Int. Ed., 2011, 50, 5120;
This journal is © The Royal Society of Chemistry 2019
Green Chem.

View Article Online
Paper
Green Chemistry
49 (a) Z. Wang, Z. Li, T. Lei, M. Yang, T. Qi, L. Lin, X. Xin, 60 K.-V. Tran and D. Bickar, J. Org. Chem., 2006, 71, 6640.
A. Ajayebi, Y. Yang, X. He and X. Yan, Appl. Energy, 2016, 61 R. Adams and A. F. Thal, Benzyl cyanide, Org. Synth., 1922,
183, 170; (b) M. A. F. Delgove, A. B. Laurent, J. M. Woodly,
S. M. A. De Wildeman, K. V. Bernaerts and Y. van der Meer, 62 R. Adams and A. F. Thal, Benzyl cyanide, Org. Synth., 1922,
ChemSusChem, 2019, 12, 1349. 2, 9, collective vol. 2, p63.
50 (a) C. Koroneos, A. Dompros, G. Roumbas and 63 (a) J. Y. Bae, S-H. Park, W-X. Cai and J-H. Zhen, Preparation
2, 59, collective vol. 1, p36.
N. Moussiopoulos, Int. J. Hydrogen Energy, 2004, 29, 1443;
(b) S. Rivas, A. M. Raspolli-Galletti, C. Antonetti, V. Santos
and J. C. Parajó, J. Wood Chem. Technol., 2015, 35, 315.
51 R. Arvidsson, A.-M. Tillman, B. A. Sandén, M. Janssen,
A. Nordelöf, D. Kushnir and S. Molander, J. Ind. Ecol.,
2018, 22, 1286.
52 H. H. Khoo, L. L. Wong, J. Tan, V. Isoni and P. Sharratt,
Resour., Conserv. Recycl., 2014, 95, 174.
53 Environmental Product Declaration (EPD) – PCR Basic
Module – Basic Chemicals CPC 34 (v3.0), 2017.
of glycol ether (line 0027), JPH07206744A, 1995;
(b) H. W. Richardson, Copper Compounds, Ullmann’s
Encyclopedia of Industrial Chemistry, Wiley-VHC, Weinheim,
2005; (c) G. Zhou, L. Feng, Q. Sun, A. Wang, T. Song and
Q. Qi, The method of producing high selectivity tri-
ethylamine (example 4, line 0060–0062), CN104370748B,
2016.
64 (a) M. I. Bruce and J. R. Knight, J. Organomet. Chem., 1968,
12, 411; (b) B. A. Persson, A. L. E. Larsson, M. Le Ray and
J.-E. Bäckvall, J. Am. Chem. Soc., 1999, 121, 1645.
54 M. Fauré, C. Saccavini and G. Lavigne, Chem. Commun., 65 M. J. Mays, M. J. Morris, P. R. Raithby, Y. Shvo and
2003, 1578. D. Czarkie, Organometallics, 1989, 8, 1162.
55 (a) H. Remy, Z. Anorg. Allg. Chem., 1924, 137, 365; 66 O. Jolliet, M. Margni, R. Charles, S. Humbert, J. Payet,
(b) W. P. Griffith, Platinum Metals Rev., 1975, 19, 60.
56 P. Nuss and M. J. Eckelman, Met. Environ. Impacts, 2014, 9,
e101298.
G. Rebitzer and R. Rosenbaum, Int. J. Life Cycle Assess.,
2003, 8, 324.
67 Fifth
Assessment
Report,
The
Physical
Science
57 C. Cesari, L. Sambri, S. Zacchini, V. Zanotti and
R. Mazzoni, Organometallics, 2014, 33, 2814.
Basis, Intergovernmental Panel on Climate Change,
2013.
58 D. X. Klein, T. A. Girard and H. R. Johnson; assignors to 68 (a) J. H. Choi, N. Kim, Y. J. Shin, J. H. Park and J. Park,
Heyden Chemical Corporation, New York, N.Y., a corpor-
ation of Delaware, US2658920, 1951.
59 J. Safari, N. M. Arani and A. R. Esfahani, Asian J. Chem.,
2011, 23(6), 495–498.
Tetrahedron Lett., 2004, 45, 4607; (b) D. G. Hanna,
S. Shylesh, P. A. Parada and A. T. Bell, J. Catal., 2014, 311,
52; (c) D. He and I. T. Horváth, J. Organomet. Chem., 2017,
847, 263.
Green Chem.
This journal is © The Royal Society of Chemistry 2019