Selective hydrodeoxygenation of hydroxyacetophenones to ethyl-substituted phenol derivatives using a FeRu?SILP catalyst

Article abstract of DOI:10.1039/d0cc03695a

The selective hydrodeoxygenation of hydroxyacetophenone derivatives is achieved opening a versatile pathway for the production of valuable substituted ethylphenols from readily available substrates. Bimetallic iron ruthenium nanoparticles immobilized on an imidazolium-based supported ionic liquid phase (Fe25Ru75?SILP) show high activity and stability for a broad range of substrates without acidic co-catalysts. This journal is

Full text of DOI:10.1039/d0cc03695a

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Selective hydrodeoxygenation of
hydroxyacetophenones to ethyl-substituted
Cite this:DOI: 10.1039/d0cc03695a
phenol derivatives using a FeRu@SILP catalyst†
Received 25th May 2020,
Accepted 13th July 2020
Lisa Goclik,ab Lisa Offner-Marko,ab Alexis Bordet *a and Walter Leitner
*
ab
DOI: 10.1039/d0cc03695a
rsc.li/chemcomm
The selective hydrodeoxygenation of hydroxyacetophenone deri- of hydrogenating and deoxygenating aromatic ketones, while
vatives is achieved opening a versatile pathway for the production leaving the aromaticity of the ring untouched (Fig. 1A). Recent
of valuable substituted ethylphenols from readily available sub- efforts resulted in the development of catalysts with promising
strates. Bimetallic iron ruthenium nanoparticles immobilized on an performance for the selective hydrogenation and hydrodeoxygena-
imidazolium-based supported ionic liquid phase (Fe25Ru75@SILP) tion of aromatic substrates.10,11 In particular, we introduced a
show high activity and stability for a broad range of substrates bifunctional catalyst composed of bimetallic iron–ruthenium
without acidic co-catalysts.
nanoparticles immobilized on an acid-functionalized supported
ionic liquid phase (Fe25Ru75@SILP + IL-SO3H) and demonstrated
Although substituted ethylphenols have attracted considerable its excellent activity, selectivity, and stability for the hydrodeoxy-
attention due to their importance as building blocks for the genation of benzylic and non-benzylic ketones.10a However,
production of fine chemicals,1 polymers,2 and pharmaceuticals,3 despite its versatility, this bifunctional catalyst cannot be
their synthesis remains particularly challenging. The Friedel– employed to convert hydroxyacetophenone derivatives due to
Crafts alkylation of phenols4 to produce ethylphenol derivatives competing acid-catalyzed side-reactions.12 Now we report that
is indeed difficult and requires harsh conditions, since the –OH we were able to close this gap in the substrate scope by utilizing
group of phenol coordinates with classical Lewis acidic catalysts bimetallic Fe25Ru75 nanoparticles immobilized on a non-acidic
and prevents the reaction. In addition, this pathway offers poor imidazolium-based SILP support. The mesomeric effects activat-
chemo- and regioselectivity as well as a very limited substrate ing the ketone and stabilizing the intermediate carbocation were
scope. Several alternative methods providing access to ethylphe- found to be the key to high hydrodeoxygenation activity under the
nol derivatives have been developed, including in particular the optimized acid-free conditions. Thus, a broad range of hydroxya-
hydrogenolysis of diarylethers and lignin model substrates,5 and cetophenone derivatives were effectively and selectively hydro-
the hydrogenation of vinylphenol derivatives.6 These approaches deoxygenated using the Fe25Ru75@SILP catalyst, giving access to
suffer from significant limitations, however, such as low catalyst
activity,5b,c,6a low selectivity,5a,e, f low stability/recyclability,5a,d, f or
limited substrate scope.5c–e The high costs of vinylphenols are
prohibitive for their use as starting materials in most commer-
cial applications.6 In this context, the hydrodeoxygenation of
easily accessible hydroxyacetophenone derivatives – obtained for
example through Friedel–Crafts acylation,7 Fries rearrangement8
or oxidative depolymerization of lignin9 – could offer an
attractive alternative. Robust synthetic methods based on these
transformations require the design of catalytic systems capable
a Max Planck Institute for Chemical Energy Conversion, Stiftstr. 34-36,
¨
45470 Mulheim an der Ruhr, Germany. E-mail: alexis.bordet@cec.mpg.de,
walter.leitner@cec.mpg.de
b
¨
Institut fur Technische und Makromolekulare Chemie, RWTH Aachen University,
Fig. 1 (A) Pathway for the synthesis of alkyl phenol derivatives through
hydrodeoxygenation of hydroxyacetophenones. (B) Examples of applica-
tions for substituted alkyl phenols in pharmaceutical products.
Worringerweg 2, 52074 Aachen, Germany
† Electronic supplementary information (ESI) available. See DOI: 10.1039/
d0cc03695a
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Table 1 Hydrodeoxygenation of 1 with different catalytic systems
a wide range of ethylphenols, which are very difficult to obtain
through other synthetic methods. This opens a new retrosynthetic
pathway for the production of valuable substituted ethylphenols
from widely accessible substrates (Fig. 1).
The Fe25Ru75@SILP catalyst (Fig. 2a) was synthesized
through an organometallic approach following a recently
reported procedure (see ESI† for details).10b The use of the
imidazolium-based SILP is crucial for the formation of small,
well-dispersed and homogeneously alloyed Fe25Ru75 NPs under
these conditions, as well as for their efficient stabilization
through electrosteric interactions. TEM analysis evidenced
the formation of small and well-dispersed nanoparticles with
an average size of 3.3 nm (Fig. 2b). The catalyst was further
characterized by BET measurements, giving a surface area of
a
a
a
Entry Catalyst
Xa [%] Y1c [%] Y1d–f [%] Y1g,h [%]
1
2
3
Fe100@SILP
Ru100@SILP
Fe25Ru75
SILP+IL-SO3H
Fe25Ru75@SILP 499
0
499
499
0
0
53
0
0
0
91b
0
@
47c
4
499
0
0
Reaction conditions: catalyst (37.5 mg, metal content: 0.015 mmol),
substrate (0.375 mmol, 25 eq.), solvent (0.5 mL), 175 1C, H2 (50 bar),
16 h, 500 rpm. Determined by GC-FID using tetradecane as an internal
standard. Products are 1g (41%), 1h (50%), dimers (9%). Other pro-
ducts: 1d (30%), 1e (12%) and 1f (5%).
170 m2 ꢀ1, corresponding to about 50% of the undecorated
g
a
silica. SEM-EDX analysis indicated a metal loading of 0.4 mmol gꢀ1
and a Fe : Ru ratio of 25 : 75 (ꢁ5%), well in agreement with the
theoretical values (Table S1, ESI†). The oxidation state and alloy
extent of the Fe25Ru75 NPs in Fe25Ru75@SILP were investigated
b
c
by XANES and EXAFS already in a previous study, evidencing acetophenone derivatives under standard conditions (Table S2,
zerovalent Fe and Ru atoms organized in a slightly homophilic ESI†) Interestingly, significant activity was observed only for
bimetallic structure.10b
acetophenone derivatives possessing functional groups providing
The catalytic properties of Fe25Ru75@SILP and several refer- mesomeric stabilization (–OH, –OMe, –OPh, –NH2, etc.), suggest-
ence catalysts were investigated using 4-hydroxyacetophenone ing the importance of mesomeric effects on the hydrodeoxygena-
(1) as model substrate (Table 1). Monometallic Fe@SILP pre- tion. For the substrates, which cannot provide this stabilisation,
sented no activity under these conditions. Ru@SILP lead to the the hydrogenation products (2a, 3a, 5a, 6a) were mostly observed.
full but unselective conversion of the substrate, with the To further study the importance of the mesomeric stabilisation,
production of a mixture of 4-(1-hydroxy-ethyl)cyclohexan-1-ol 20- and 30-hydroxyacetophenone were considered as substrates
(1g, 41%), 40-ethylcyclohexanol (1h, 50%), and dimers (9%). As (Table S3, ESI†). With the hydroxyl group located in ortho- (13) or
expected, the aromaticity of the ring was not conserved. The use para- (1) positions, the conversion, selectivity and yield of the
of the recently reported Fe25Ru75@SILP+IL-SO3H catalyst10a target products are over 99%. In the case of the meta-substituted
resulted in low selectivity and low yield of the desired product substrate 30-hydroxyacetophenone (12), the conversion is signifi-
(1c, 53%). Other products observed include phenol (1d, 30%), cantly lower with 39%. The selectivity remains however excellent
2040-ethylphenol (1e, 12%) and 20-ethylphenol (1f, 5%). The for- (95%). The results confirm that mesomeric effects play a key role
mation of these compounds is due to several acid-catalysed side- activating the substrates and stabilizing the intermediate carboca-
reactions such as protiodeacylation,12 Friedel–Crafts acylation and tion. Despite a lower reactivity, the excellent selectivity observed
hydrodeoxygenation. In contrast, the hydrodeoxygenated pro- with 30-hydroxyacetophenone (12) as substrate suggests that
duct 1c was yielded quantitatively using Fe25Ru75@SILP. The under optimized reaction conditions Fe25Ru75@SILP could effec-
hydrogenation selectivity observed here is in agreement with tively produce meta-ethyl phenols, which are extremely difficult to
our previous studies showing that alloying Fe and Ru in this obtain through other pathways.
specific 25 : 75 ratio generates synergistic effects leading to a
Based on these promising results, the Fe25Ru75@SILP
significant enhancement of the CQO hydrogenation rate as catalyst was applied to a scope of hydroxyacetophenone deri-
compared to monometallic Ru, while the aromatic hydrogenation vatives with a wide range of substituent patterns (Table 2). All
is prevented.10a,b To investigate the versatility of Fe25Ru75@SILP as the substrates considered were effectively hydrodeoxygenated
a hydrodeoxygenation catalyst, its activity was tested for various under these conditions, producing substituted ethylphenols in
excellent selectivity and yields. Interestingly, the products 15c,
17c and 18c are building blocks used directly in the synthesis of
the pharmaceutical compounds highlighted in Fig. 1B.3b–d
Substrates 19 and 20 can be obtained from lignin,13 evidencing
the capacity of Fe25Ru75@SILP to convert biomass-derived
substrates to value added chemicals. Furthermore, the synth-
esis of products 14c and 15c was, to the best of our knowledge,
not reported before, and this is thus the first synthetic method
providing these compounds in high yields and selectivity. The
production of 22c in excellent yield indicates that the length
Fig. 2 Fe25Ru75@SILP; (a) illustration of the catalytic system; (b) TEM
image.
of the chain does not affect the reactivity. This opens the way to
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Table 2 Hydrodeoxygenation of hydroxyacetophenone derivatives
The results show that the conversion of hydroxyacetophenone
derivatives possessing electron-donating substituents is signifi-
cantly faster than for those possessing electron-withdrawing func-
tionalities. This is in agreement with previous observations.11d The
corresponding alcohols and olefins were observed in the pro-
duct mixtures at these shortened reaction times, supporting a
hydrogenation/dehydration/hydrogenation sequence as plausi-
ble reaction pathway. The nature and proportion of the inter-
mediates observed during the reactions strongly depends on
the nature of the substituents, albeit no clear trend could be
identified regarding the electron donating/withdrawing proper-
ties of the substituents. This most likely reflects different
effects of the substituents on the rates of the individual steps
of the sequence. To get further insight into the hydrodeoxygena-
tion activity of Fe25Ru75@SILP, a time profile was recorded using
40-hydroxyacetophenone (1) as model substrate (Fig. S1, ESI†).
The reaction temperature was reduced to 120 1C in order to
slow down the reaction and allow the observation of the inter-
mediates. Under these conditions, the substrate was fully con-
verted after 3 h, giving 1c in quantitative yield. 4-Vinylphenol (1b)
was the only intermediate observed, suggesting a very fast deox-
ygenation of the alcohol intermediate 1a. Prolonging the reaction
time to 16 h did not change the product distribution, highlighting
the excellent selectivity of Fe25Ru75@SILP. Interestingly, the con-
version of the substrate (and formation of 1c) appears to become
faster with time, indicating that the reaction rate increases when
the concentration of the substrates decreases. This presumably
reflects the influence of the release of water during the reaction,
rather than a true negative kinetic order with regards to the
substrate. Mesitylene is a hydrophobic solvent, and the water
released during hydrodeoxygenation accumulates on the catalyst,
increasing progressively the polarity of the medium around the
NPs. Consequently, the affinity of the polar substrate 1 for
adsorption at the Fe25Ru75@SILP material also increases, thus
resulting in an increase of the local substrate concentration
around NPs and an acceleration of the reaction, even though
the global substrate concentration decreases. The accumulation
of water on the catalyst during the reaction was confirmed by IR
spectroscopy, supporting this assumption (Fig. S2, ESI†). Similar
increases in reaction rate due to high local concentrations of
substrates has previously been reported for SCILL-type catalysts
where the substrates are more soluble in the IL layer than in the
solvent used.15 Recording a time profile in the presence of
deliberately added small amounts of H2O resulted indeed in
much higher initial activity, strongly supporting this hypothesis
(Fig. S3, ESI†). The release of water as a co-product of the reaction
is thus beneficial in this case, since it counterbalances the global
decrease of the substrate concentration with time by increasing its
affinity (and thus local concentration) around the active sites. This
Entry
1
Substrate
Product
Xa [%]
97
Sa [%]
Y*a [%]
97
499
2
3
499
499
96b
96b
96 (81)
96
4
5
6
499
499
499
499
499
499
499
499 (88)
499 (85)
7
8
499
499
499
499
499 (91)
499 (98)
9
96
96c
92
10
499
499
499 (91)
Reaction conditions: catalyst (37.5 mg, metal content: 0.015 mmol),
substrate (0.375 mmol, 25 eq.), solvent (0.5 mL), 175 1C, H2 (50 bar), 16
a
h, 500 rpm. Determined by GC-FID using tetradecane as internal
b
standard. * Isolated yield in parentheses. By-products is 4-ethylphenol
c
(4%). By-product is methyl 2-hydroxy-5-(1-hydroxyethyl)benzoate (4%).
X = conversion, S = selectivity, Y = yield.
the synthesis of long chain alkyl phenols, which are key reagents behaviour is in contrast to most of the deoxygenation catalysts
for the production of alkylphenol ethoxylates, a very important previously reported, which tend to lose their activity due to the
class of non-ionic surfactants.14 Comparing the prices of the accumulation of water.5a,16 The possibility to recycle the Fe25R-
substrates and products at classical providers shows that in the u75@SILP catalyst was studied using 40-hydroxyacetophenone (1)
vast majority the cases, the ethylphenol derivatives are much more as substrate. Fully constant conversion and selectivity towards
expensive than the starting hydroxyacetophenones, confirming the formation of 4-ethylphenol (1c) were obtained in five con-
the value-adding potential through this pathway (Table S4, ESI†). secutive runs without any make-up or regeneration (Fig. S4, ESI†).
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After 5 cycles, the catalyst was characterized by BET, TEM and
SEM-EDX (Table S1, ESI†). BET analysis indicated that the textural
properties of the catalyst remained largely unaffected. According to
TEM analysis, the size of the NPs and their dispersion on the
support did not change significantly. In addition, SEM-EDX did not
evidence any significant leaching of the metal or any modification of
the Fe : Ru ratio under these conditions. These results evidence the
excellent stabilization of the bimetallic NPs by the SILP.
In conclusion, the organometallic approach to graft bime-
tallic Fe25Ru75 nanoparticles on imidazolium-modified silica
materials produces a Fe25Ru75@SILP catalyst with excellent
properties for the hydrodeoxygenation of hydroxyacetophenone
derivatives. The presence of the OH-substituent allows meso-
meric stabilization of the carbocation intermediates and is
essential to observe high hydrodeoxygenation activity under
these non-acidic conditions. Achieving the hydrodeoxygenation
in the absence of acidic co-catalysts is beneficial for this
particular class of substrates, since it prevents side-reactions
such as protiodeacylation. Synthesized through a molecular
approach, the Fe25Ru75@SILP catalyst was found to be highly
active and stable for the selective conversion of a wide range of
hydroxyacetophenones with various functional groups, opening
a versatile route for the production of value-added substituted
ethylphenols from widely available substrates. Preliminary
results indicate that the same retrosynthetic design is applic-
able to ethylaniline derivatives and long chain alkyl phenols,
which are key intermediates in the synthesis of pharmaceuti-
cals and non-ionic surfactants, respectively.
The authors acknowledge financial support by the Max
Planck Society and by the Deutsche Forschungsgemeinschaft
(DFG, German Research Foundation) under Germany’s Excellence
Strategy – Exzellenzcluster 2186 ‘‘The Fuel Science Center’’ ID:
390919832. Furthermore, the authors thank Alina Jakubowski,
¨
Annika Gurowski, Justus Werkmeister and Norbert Pfander
(MPI-CEC, Mu¨lheim/Ruhr) for their support with the analytics.
Open Access funding provided by the Max Planck Society.
ˇ
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Conflicts of interest
There are no conflicts to declare.
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