Multifunctional supported bimetallic catalysts for a cascade reaction with hydrogen auto transfer: Synthesis of 4-phenylbutan-2-ones from 4-methoxybenzyl alcohols

Article abstract of DOI:10.1039/c7cy00184c

We report the one-pot tandem synthesis of 4-(4-methoxyphenyl)butan-2-one directly from 4-methoxybenzyl alcohol and acetone using a multifunctional supported AuPd nanoalloy catalyst. This one-pot synthesis involves dehydrogenation, aldol condensation and hydrogenation of CC. In this supported AuPd catalyst, the bimetallic sites catalyse the dehydrogenation and hydrogenation steps and, in combination with the support, catalyse the C-C coupling (aldol) process. This supported bimetallic catalyst is also effective in utilizing hydrogen from the dehydrogenation reaction for the hydrogenation of 4-(4-methoxyphenyl)but-3-en-2-one to 4-(4-methoxyphenyl)butane-2-one via a hydrogen auto transfer route. These multifunctional catalysts were characterised using transmission electron microscopy, X-ray diffraction and X-ray photoelectron spectroscopy.

Full text of DOI:10.1039/c7cy00184c

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Nowicka, J. M. Douthwaie, S. Iqbal, P. Miedziak, J. Edwards, G. Brett, Q. He, D. W. Knight, D. Morgan, H.
Alshammari, D. Bethell, M. Sankar and G. Hutchings, Catal. Sci. Technol., 2017, DOI:
10.1039/C7CY00184C.
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Catalysis Science & Technology
Multifunctional supported bimetallic catalysts for a cascade reaction with hyDdOrIo: 1g0e.1n03V9ie/wC7ACrtYic0le0O18nl4inCe
auto transfer: synthesis of 4-phenylbutan-2-ones from 4-methoxybenzyl alcohols
Moataz Morad,a,b Ewa Nowicka,a Mark Douthwaite,a Sarwat Iqbal,a Peter Miedziak,a Jennifer
K. Edwards,a Gemma L. Brett,a Qian He,a David Morgan,a Hamed Alshammari,a,c Donald
Bethell,a David W. Knight,a Meenakshisundaram Sankara* and Graham J. Hutchingsa**
aCardiff Catalysis Institute, School of Chemistry, Cardiff University, CF10 3AT Cardiff,
United Kingdom.
bChemistry Department Faculty of Science, Umm al-qura University, PO Box 21955, 9264
Makkah, Saudi Arabia.
cChemistry Department, Faculty of Science, Ha'il University, P. Box 2440, 81451 Ha'il,
Saudi Arabia.
* Dr. Meenakshisundaram Sankar, Cardiff Catalysis Institute, School of Chemistry, Cardiff
University, Cardiff, CF10 3AT (UK), Fax: (+44) 2920-874-030, E-mail:
sankar@cardiff.ac.uk.
** Prof Graham J. Hutchings, Cardiff Catalysis Institute, School of Chemistry, Cardiff
University, Cardiff, CF10 3AT (UK), Fax: (+44) 2920-874-030, E-mail: hutch@cardiff.ac.uk

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DOI: 10.1039/C7CY00184C
Abstract
We report the one-pot tandem synthesis of 4-(4-methoxyphenyl)butan-2-one directly from 4-
methoxybenzyl alcohol and acetone using a multifunctional supported AuPd nanoalloy
catalyst. This one pot-synthesis involves dehydrogenation, aldol condensation and
hydrogenation of C=C. In this supported AuPd catalyst, the bimetallic sites catalyse the
dehydrogenation and hydrogenation steps and, in combination with the support, catalyse the
C-C coupling (aldol) process. This supported bimetallic catalyst is also effective in utilizing
hydrogen from the dehydrogenation reaction for the hydrogenation of 4-(4-
methoxyphenyl)but-3-en-2-one to 4-(4-methoxyphenyl) butane-2-one via a hydrogen auto
transfer route. These multifunctional catalysts were characterised using Transmission
Electron Microscopy, X-ray diffraction and X-ray Photoelectron Spectroscopy.
Keywords: Supported AuPd catalysts, Multifunctional catalysts, AuPd nanoparticles,
Cascade reactions, one-pot synthesis, hydrogen autotransfer reaction.

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DOI: 10.1039/C7CY00184C
Introduction
4-(4-methoxyphenyl)butan-2-one (4), also known as “raspberry ketone,” is an important fine
chemical and is used extensively in several consumer products such as (a) a raspberry scent,
(b) a food additive, (c) an insect attractant and (d) in the preparation of melanin formation
inhibitors.1, 2 However, the quantities available from natural sources are exceedingly low (ca
1–4 mg per kg of raspberries) and hence an efficient synthetic route leading to 4 is in high
demand. Commercially, ketone 4-(4-methoxyphenyl)butan-2-one is prepared by Friedel-
Crafts alkylation of anisole with 4-hydroxybutan-2-one or methyl vinyl ketone (MVK) using
homogeneous or heterogeneous Lewis or Brønsted acid catalysts.3 This method produces
many side products (as a result of transalkylation, isomerization, polyalkylation and
polymerisation reactions) besides significant quantities of waste. Corma et al. proposed
another route for the synthesis of 4 using the Heck reaction between 4-methoxyiodobenzene
and methyl vinyl ketone.4 Although this is an efficient method, it is not environmentally
benign, especially as iodide is a by-product. Recently, the same group reported a one-pot
synthesis of 4-(4-methoxyphenyl)butan-2-ol (5) from 4-methoxybenzaldehyde (2)
(R1=OCH3) and acetone by combining aldol coupling and hydrogenation reactions in one-pot
(2 to 5 in Scheme 1). They compared the three processes and deduced that the tandem
synthesis, employing a multifunctional catalyst, has the smallest E factor.5
One of the grand challenges in chemistry is to develop alternative technologies to produce
chemicals in a cleaner, safer, and environmentally benign manner.6 Multi-enzymatic systems
that perform multi-step reactions in nature have inspired catalytic chemists to develop
multifunctional catalysts that can catalyse several chemical transformations in a single
reactor, known as tandem, domino or cascade reactions.7-9 This strategy helps to improve the
atom economy or the E factor (kgwaste/kgproduct) by decreasing the number of energy-intensive

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separation and purification steps of the intermediates.10 Designing a multi-functional catVaielwyAsrtticle Online
DOI: 10.1039/C7CY00184C
is a challenging task because each transformation requires different, often incompatible,
catalytic active sites (e.g. acidic and basic sites) and/or reaction conditions.11, 12 There are
examples
of bi-functional
catalysts,
including the widely used alkane
hydroisomerization/hydrocracking catalyst, in this case the metal (Pt) centre catalyses the
dehydrogenation of an n-alkane to form the corresponding olefin and H2 whilst the acidic
support (alumina or zeolite) catalyses the isomerization or cracking reactions.13 The metal
(Pt) site subsequently catalyses the hydrogenation of the branched olefins.
Following initial reports by Sinfelt on the use of bimetallic catalysts, we have reported the
application of supported gold-palladium bimetallic catalysts for the aerobic oxidative
dehydrogenation of primary alcohols and the hydrogenation of levulinic acid (LA) to -
valerolactone (GVL).14-16 In these examples, we found that alloying two metals substantially
increased the activity and/or selectivity compared to their monometallic counterparts. A
number of other bimetallic catalysts have also been reported to be exceptionally active and/or
selective for oxidation, hydrogenation, hydrochlorination, reforming reactions and biomass
conversion.17, 18 Recently we found that for the aerobic oxidative dehydrogenation of benzyl
alcohol, supporting the gold-palladium nanoalloys on MgO, the disproportionation pathway,
which leads to the undesired formation of toluene, is completely inhibited, thereby increasing
the selectivity for the desired benzaldehyde to >99%.19 We further exploited the basicity of
MgO in this catalyst for the (otherwise) base-free oxidation of glycerol to glyceric acid under
mild reaction conditions.20, 21
In this work, we report an efficient multi-functional catalyst for the tandem synthesis of 4-(4-
methoxyphenyl)butan-2-one (4) starting from 4-methoxybenzyl alcohol (1) instead of 4-

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methoxybenzaldehyde (2) (Scheme 1). Adding an initial dehydrogenation reactioVniew iAsrticle Online
DOI: 10.1039/C7CY00184C
advantageous because alcohols are generally more readily available starting materials than
aldehydes and inherently they are more stable. Importantly, we further report that the
hydrogen generated from this dehydrogenation reaction is effectively used in the
hydrogenation reaction (3 to 4) using a hydrogen auto-transfer strategy. Moreover, we
demonstrate, using different derivatives of benzyl alcohol, this one-pot reaction proceed in a
similar way as 4-methoxybenzyl alcohol.
Experimental
Catalyst Preparation
Pre-treatment of nano-MgO
Mg(OH)2 (Sigma Aldrich, 50nm) was heated at 723K for 5h with a heating ramp rate of 5K
min-1 to form nano-MgO.
Synthesis of Au-Pd nanoparticles supported via the sol-immobilizaiton technique
Au–Pd bimetallic catalysts were prepered using TiO2 (Sigma Aldrich), MgO (BDH),
Mg(OH)2 (nanopowder, <100 nm, Sigma Aldrich), and Al2O3 (Sigma Aldrich) as support.
Only the Mg(OH)2 support was pre-treated (calcined) at 673K for 5 h under static air (heating
rate 5K min-1) to form nano-MgO. The supported bimetallic catalysts were prepared using the
following sol-immobilisation method: aqueous solutions of PdCl2 (Johnson Matthey, 6
mg/ml) and HAuCl4·3H2O (Sigma Aldrich, 12.25 mg/ ml) were freshly prepared. Polyvinyl
alcohol (PVA) (1 wt% solution, Aldrich, Mw = 10 000, 80% hydrolyzed) was added to the
solution and stirred with HAuCl4·3H2O for 15 min. 0.1 M of NaBH4 (>96% Aldrich,
NaBH4/Au (mol/mol = 5)) was freshly prepared and then added to the solution to form a dark

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brown sol. The mixture was stirred for 30 min and adjusted to pH 1 by the drop-wise addition
DOI: 10.1039/C7CY00184C
of sulphuric acid. The supports was added to mixture and the slurry was then stirred for 1 h.
Following this the catalyst was recovered by filtration, washed with 2 L distilled water and
dried at 383K overnight. The 0.5% Au–Pd/ Mg(OH)2 catalyst was then treated at 723K for 5h
under N2 (ramp rate 20 K min-1) to form 0.5% Au-Pd/MgO. All these catalysts were used
without any further treatment.
Catalytic testing
All the catalytic reactions were performed in a 50 mL stainless steel high-pressure autoclave
reactor (PARR® Autoclaves) fitted with an overhead stirrer. In a typical reaction, the reactor
was charged with requisite amount of the catalyst, the reactants (alcohol and acetone) and the
internal standard (mesitylene). Then the reactor was purged with the appropriate gas (O2, H2,
N2) three times before pressurizing it to the requisite pressure. The stirring and heating were
started and when the temperature of the reaction mixture reached the set temperature, the
reaction is considered to have started (0 h). After a specific time, the stirring was stopped and
the reactor was immediately cooled in an ice bath until the temperature deceased below
283K. Then the reaction was opened slowly and 0.5 mL of the content was centrifuged. 0.1
mL of the clear supernatant reaction mixture was taken for GC analysis.
Quantification of the products
Initially the products were identified using a GC fitted with Mass Spectrometer. After
identifiying the products, the samples were analysed using Varian star CP-3800 GC fitted
with a column (CP-Wax 52 column, capillary, 25m, 0.35mm ID, 0.2 micron) and a FID
detector for quantification studies. Determination and calibration of the reactants and
products using GC was carried out using range of known concentrations of them to obtain

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response factor (RF) which express the relative response of components to the detectorV.ie0w.A1rticle Online
DOI: 10.1039/C7CY00184C
ml of reaction mixture was used for GC analysis. A sample (0.02µl) was auto-injected into
the GC without addition of any further material as the reaction was performed in the presence
of internal standard (mesitylene). Conversion (X) was calculated following the equation:
X = (Sin-Sout)/(Sin)*100%
Selectivities were calculated taking into account only identified products. Unidentified
products accounted for 20 to 30% of all products (depending on the reaction). Those were not
taken into account during the analysis, resulting in carbon mass balance of 70-80%.
Selectivity was calculated based on the following equation:
SP = (P / ΣPidentified) *100%
Catalyst Characterisation
Powder X-ray diffraction: Powder X-ray diffraction (XRD) was recorded using a
PANalytical X’Pert Pro system fitted with a CuKα X-ray source run at 40 kV and 40 mA. An
X’Celerator detector was used in order to assess the scattered media. Each sample was
scanned from 2θ = 10 º to 80 º for 30 minutes. Prior to analysis, catalysts were ground into a
fine powder and loaded onto a silicon wafer. The corresponding results were compared
directly with the data held in the ICDD library.
Transmission Electron Microscopy: Transmission electron microscopy (TEM) was carried
out using a JEOL JEM-2100 with a LaB6 filament operating at 200 KV. Powdered catalyst
samples were dry dispersed lacey carbon films over a 400 mesh copper grid.
Microwave Plasma Atomic Emission Spectroscopy (MP-AES): Analysis was conducted
using an Agilent 4100 MP-AES. Au content was analysed using two emission lines. A known
mass of AuPd/MgO was added to dilute aqua regia solution (50 mL of 20% aqueous

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solution) and left to digest overnight. The samples were filtered using PTFE filters (Acrodisc
DOI: 10.1039/C7CY00184C
PVDF 0.45 μl). Samples were introduced into a stream of nitrogen plasma via a single pass
spray chamber at a pressure of 120 kPa in the absence of any air injection. The instrument
was calibrated with 2.5 ppm, 5 ppm and 10 ppm of Au standards. Samples were tested three
times and an average of the three results was taken.
Inductively Coupled Plamsa (ICP): ICP analyse was performed using an Agilent ICP-MS
7900 instrument. Quantitative analyses of the aqueous solutions containing metal ions were
carried out using calibration plots of certified standards (from Agilent). Each analysis was
performed in duplicate.
Thermal Gravitation Analysis (TGA): TGA was conducted using a Setram Labsys
TGA/DTA instrument. Catalyst samples were heated from 30 to 800 ºC under flowing air (15
mL min-1) at a heating rate of 10K min-1.
X-ray Photoelectron spectroscopy (XPS): A Thermo k-Alpha+ photoelectron spectrometer
equipped with monochromatic Al radiation was used in this work. Charge neutralisation was
achieved using a combination of low energy electrons and argon ions. Due to changes in the
C(1s) level due to the heat treatments used in the study calibration to this core level was
found to be inconsistent, therefore calibration was performed using the Mg(1s) line taken to
be 1303.9 eV for MgO.22
Results and Discussion
Initially we used aldehyde 2 (R1=OCH3) as the starting material to identify a suitable active
support for the aldol condensation step. Basic metal oxides such as MgO (BDH), ZnO (Sigma
Aldrich) and La2O3 (Sigma Aldrich) were tested as received; for comparison TiO2 (Degussa

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P-25) and Al2O3 (Sigma Aldrich) were also tested (see supporting information TableVSiew1A)r.ticle Online
DOI: 10.1039/C7CY00184C
Surprisingly, the basic metal oxides are not effective for this transformation. This is not due
to poisoning of the basic sites by CO2 as, even after calcination at 673 K there was no
improvement in their catalytic activities. Al2O3 and TiO2, however, show appreciable abilities
to catalyse this coupling, possibly via acid catalysed aldol condensation reaction. In the next
stage, we supported AuPd nanoalloy particles, which were between 1-7 nm, on all these
supports using a sol-immobilization technique.19 In addition to these supports, a nano MgO,
produced by the calcination of commercial nano Mg(OH)2 at 673 K was also used to support
23
these AuPd nanoalloys. All supported AuPd catalysts were tested for the conversion of 4-
methoxybenzaldehyde (2) to 4-(4-methoxyphenyl)butan-2-one (4). Here we sought to
combine the coupling reaction with hydrogenation of the C=C bond in the resulting α, β
unsaturated ketone 3. For comparison, we also prepared monometallic Au and Pd catalysts
and tested these in this one-pot synthesis (see supporting information Table S2). The results
indicate that the nature of the metallic site and the metal oxide support play crucial roles in
determining the reaction pathways and hence the selectivity towards the products.
Monometallic Pd supported on TiO2 (5%Pd/TiO2) is extremely active and selective for the
transformation of 2 into 4-methylanisole (6) with 100% conversion and 99% selectivity,
presumably by sequential reduction to the corresponding benzyl alcohol 1 and its
hydrogenolysis. This is a totally different pathway compared to the formation of 3 and 4. A
different 1%Pd/TiO2 catalyst was prepared by conventional wet-impregnation method and
was used for this reaction. This catalyst is less active than the previous catalyst (5%Pd/TiO2),
however, it leads predominantly to formation of ketone 4 with no trace of anisole 6. This
change in reaction pathway between 1%Pd/TiO2 and 5%Pd/TiO2 could be because of the
difference in the acidity of these two catalysts. The Pd precursor solution is made by
dissolving solid PdCl2 in 0.58M HCl solution to form palladate because solid PdCl2 is

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sparingly soluble in cold water, whereas palladate is. This means that higherDPOId: 10l.o10a3d9/iCn7gCY00184C
increases the HCl concentration in the catalyst synthesis medium. This could have resulted in
the increased acidic surface of the catalyst for higher Pd loading which results in the
hydrogenolysis pathway rather than the aldol condensation pathway. Another explanation is
that metal catalysed reactions (hydrogenation & hydrogenolysis) dominate in the competition
for 2 when catalysts with higher metal loading. Metal oxide catalysed aldol condensation
dominates when the catalysts with lower metal loading are used. However, the role of the
nature of the metal particles (specifically size and structure) in determining the reaction
pathways cannot be ruled out at this stage. A further in-depth investigation to study this
interesting behaviour is currently in progress. All other observations are understandable in
terms of the flow chart in Scheme 1.
When bimetallic 1%AuPd/TiO2 was used for this reaction, the conversion increased to 63%
compared to 16% for the monometallic Pd catalyst prepared by the same method. However,
the selectivity to 4 dropped dramatically to 16% with reduction to alcohol 1 becoming the
major pathway (62%). We also used Al2O3 as the support for the AuPd nanoalloys since it
was found to be active for the transformation of 2 into 3 in the absence of a metal (Table 1).
Surprisingly, this catalyst is less active, with only 7% conversion and a higher selectivity for
reduction to alcohol 1. However, when 1%AuPd/MgO was used as the catalyst, the
selectivity to ketone 4 increased markedly to 58% with 100% conversion. This indicates that
MgO-supported catalysts are preferred for this reaction and validates the initial hypothesis of
this work. We then employed nano-MgO 23, as support for the AuPd nanoalloys and
decreased the metal content by 50% to 0.5wt%. As shown in Figure S2, XRD confirmed that
the final phase of the support was in fact MgO. The final heat treatment conducted under
flowing N2 appears to result in a complete phase change from the Mg(OH)2 after the

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immobilisation of Au and Pd to MgO. Both catalysts displayed 100% conversion but for this
DOI: 10.1039/C7CY00184C
new catalyst there was a marginal increase in the selectivity to the desired product 4. For
comparison we used the monometallic counterparts of this catalyst [0.5%Au/MgO and
0.5%Pd/MgO] for this reaction and found 0.5%Pd/MgO to be the most effective (see
supporting information Table S2). The most interesting observation is that MgO alone does
not catalyse the aldol coupling reaction (see supporting information Table S1); however,
when combined with metal nanoparticles, it is highly effective. This is completely reversed in
the case of Al2O3, where the metal oxide alone is active for the coupling reaction whereas
AuPd supported on Al2O3 is not. These two examples indicate that the active sites for these
two reactions (coupling and hydrogenation) are interdependent: the metal sites appear to
promote the catalytic activities of metal oxide sites for the coupling reactions.
Inspired by our discovery that supported AuPd nanoalloys are extremely active for the
selective oxidative dehydrogenation of benzyl alcohol to benzaldehyde15, we then
investigated the tandem synthesis of ketone 4 (R2= CH3) directly from alcohol
1( R1=OCH3).The results are presented in Table 1. Initially we used 1%AuPd/TiO2 and
performed the oxidative dehydrogenation reaction (step 1) under O2 pressure at 398 K for 3h
resulting in 100% conversion with selectivities of 64% and 34% for 2 (aldehyde) and 3
(enone) respectively. The reaction mixture was then hydrogenated (step 3) under a hydrogen
atmosphere (after purging the reaction mixture with N2 thoroughly) at 398 K for 2 h. The
product mixture contained mostly anisole 6 (57%) together with small amounts of ketone 4
(27%) and alcohol 5 (14%). This catalyst, although very suitable for the oxidative
dehydrogenation reaction is not effective for either the coupling or hydrogenation reactions.
Instead, it catalyses the hydrogenation of 2 to 1 which further undergoes hydrogenolysis to 6.
To force 2 to undergo the coupling reaction instead of hydrogenation, we introduced another

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step (step 2) between steps 1 and 3 (Scheme 1), where N2 replaced the oxygen atmospheVrieewiAnrticle Online
DOI: 10.1039/C7CY00184C
a reaction carried out for 17 h at 398 K. At the end of this, the product mixture was mostly
enone 3 (76%) together with some residual aldehyde 2 (21%). This mixture was further
hydrogenated at 348 K for 2 h. This additional step increased the selectivity of 4 to 55% with
selectivities of 24 % and 21 % for 6 and 5 respectively. When monometallic Pd (1%Pd/TiO2)
was used for this reaction, the selectivity to ketone 4 increased slightly to 61%.
Finally, we used 1%AuPd/MgO for this one pot synthesis because MgO does not catalyse the
hydrogenolysis reaction. The resulting reaction mixture had a substantially lower amount of
anisole 6 (<1 %), however with a lower conversion (57%) to the desired products 3 and 4,
which were formed with selectivities of 44% and 32% respectively. The lower conversion
was deemed to be due to the hydrogenation of 2 back to 1. Instead of this three-step strategy,
we decided to perform an experiment in hydrogen atmosphere, which resulted in better
activity. After a 22h reaction at 398 K, we achieved 100% conversion with 85% selectivity
for the formation of ketone 4 (Table 2). The reaction was performed in an inert atmosphere
(N2) and the results, presented in Table-2 (last entry), clearly indicate that the hydrogen from
the dehydrogenation of alcohol is utilized for the hydrogenation of 3 to 4. This is evidently
the hydrogen auto transfer methodology (or hydrogen borrowing) proposed by Williams and
co-workers.24 This heterogeneous catalyst is one of the very few that is active for this
hydrogen auto transfer under mild reaction conditions.25, 26 This hydrogen auto transfer route
has potentially many applications, especially in the synthesis of fine chemicals.27, 28 In order
to test the substrate tolerance of this catalyst, in one reaction, benzyl alcohol was coupled
with acetone and in a different reaction, 4-metoxybenzyl alcohol and 4-tertbutylbenzyl
alcohol were coupled with 2-butanone (Table 2). In this hydrogen auto transfer reaction, we
have combined dehydrogenation, coupling and hydrogenation reactions in one-pot for the

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sequential synthesis of an industrially very important compound 4. It is interesDtiOnI:g10t.1o03V9nie/owC7tACertYic0le0O18nl4inCe
that the first step of this synthesis (dehydrogenation of 1 to 2) proceeds without any oxidant
and even in the presence of H2. Further detailed investigation is needed to understand this
observation. To the best of our knowledge, this is the first time that these three reactions
(dehydrogenation, coupling and hydrogenation) have been combined in one-pot for the
selective synthesis of this industrially very important ketone (4).
The conversion of 1 to 4 is a complex sequence of reactions and the mechanism of formation
of all these products on a multi-functional catalyst is complex. However, based on the
currently available experimental evidences, we can say that the dehydrogenation of the alcohol
1, presumably reversibly, gives aldehyde 2 + 2 Cat-H (potential side reaction –> Cat + H2). The
aldol reaction of 2 with acetone, giving unsaturated ketone 3 + water. Reaction of 3 with Cat-H,
giving 4, followed by hydrogenation of the carbonyl group to give 5, these steps being limited by
the amount of Cat-H remaining after the first step, in reactions not conducted in a hydrogen
atmosphere. With a hydrogen atmosphere, another source of Cat-H is available and the
hydrogenation steps 3 –> 4 –> 5 progress further; however, the probability of hydrogenolysis of
the alcohol, giving toluene 6 + water, in competition with dehydrogenation, is now increased.
To study the effect of the electronic nature of the substituents on the reactivity and the
versatility of this catalyst, we tested 1%AuPd/MgO using different substituted benzyl
alcohols and ketones and the results are presented in Table 2. The electron donating methoxy
group (-OCH3) in the phenyl ring displays the maximum reactivity, whereas a tertiary butyl
group suppresses the activity for both the one-pot synthesis and the hydrogen auto transfer
reaction. Acetone is a better carbonyl compared to butanone for this one-pot synthesis.

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We assessed the stability of this catalyst by reusing them for the reactions conducted under
DOI: 10.1039/C7CY00184C
both H2 and N2 and the results are presented in Table 3. A significant decrease in catalytic
performance was observed for the catalysts recovered from the reactions under both H2 and
N2. A drop in conversion from 100 % to 46 % was observed for the reaction conducted under
H2. The hydrogenation of 3 to 4 appears to have a reduced rate, which suggests that this
pathway may also be affected by the deactivation of the catalyst. Interestingly, the selectivity
to product 6 is significantly reduced during the re-use study under H2, which indicates that
the used catalyst is more selective to our desired reaction pathway. For the re-use study under
N2 no conversion was observed suggesting that the catalyst was fully deactivated.
In order to understand the reason for the catalyst deactivation, the fresh and used catalysts
have been studied. Representative TEM images of fresh and used AuPd/MgO catalysts
prepared from the nano-Mg(OH)2 are shown in Figure 1 and 2. From Figure 1, it is clearly
shown that small Au-Pd nanoparticles can be found in the fresh catalyst (Figure 1(a)) and are
still present in the used catalysts (Figure 1(b,c)), suggesting that particle agglomeration is not
likely to be responsible for deactivation. However, the support material appears to have
undergone some changes after the reaction. In the fresh catalyst, well crystallised MgO
particles can be found (Figure 2(a)), while in the catalyst used in a H2 environment, a mixture
of MgO (Figure 2(b)) and brucite Mg(OH)2 phase (Figure 2(c)) can be found. The difference
in the electron diffraction can be clearly seen in the rotational averaged profile shown in
Figure 2(d). This also agrees with the XRD data shown in Figure S3, which indicates that
there is a clear change the support during the reactions. The support in the used catalyst
appears to be partially hydroxylated whereas the fresh sample is clearly an oxide. It is known
that MgO readily converts to Mg(OH)2 in presence of H2O20, so it is likely that the
production of H2O as a result of the aldol condensation from 3 to 4 is responsible for this

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change in phase from MgO to Mg(OH)2. This subtle change in the support phaDsOeI:m10.a10y3V9iae/wCls7AoCrtYic0le0O18nl4inCe
contribute to the clear deactivation of the catalyst. Another possible source of deactivation
could be substantial quantity of organics on the surface. These organic materials, covering
some of the metallic sites, could explain the reduced reduction rate for the used catalyst. TGA
experiments revealed a large loss in mass in at approximately 630 K (Figure S1), which is not
observed in the corresponding fresh catalytic sample. ICP analysis confirmed that metal
leaching was not responsible for the deactivation . Concentrations of Au and Pd observed in
the post reaction effluents of the H2 and N2 reactions were comparable with an acetone
background blank suggesting that no Au or Pd is leached from the support during the
reactions (see supporting information Table S3).
XPS analysis of low loading Au and Pd supported materials on MgO is complicated by the
overlap of the Mg(2s) and Mg(KLL) Auger peaks respectively29, however careful fitting of
peak components and also application of “vector” techniques for determination of peak
positions and lineshapes30 can greatly enhance the information which can be elucidated from
such complicated data. For the fresh catalyst, Au is found in two states with binding energies
of 83.8 and 85.5 eV, which we attribute to metallic Au and ionic Au, potentially anchored to
defect sites such as F-centres. For the fresh sample, we have been unable to determine the Pd
content with significant confidence. Figure
Pd(3d)/Mg(Auger) fitted spectra.
3
shows the Au(4f)/Mg(2s) and
For the H2 sample, the Au is found to shift upward slightly to 84.1 and 86.3 eV respectively
and may be due to increased stabilisation of the Au by hydroxide groups31. The Pd content in
this sample can be determined by the vector method and is found have a binding energy of
335.8 eV (+/- 0.2 eV) and attributed to partially oxidised Pd or binding energy shifts due to
reduced final state screening effects32, however with the small metal loadings employed in

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this study, we are unable to perform analysis of the Pd(LMM) Auger signal to elucidate this
DOI: 10.1039/C7CY00184C
shift any further. For the N2 sample, similar Au and Pd species remain, however the intensity
of the Au species is diminished, whilst the high binding energy Au species is downshifted ca
0.4 eV potentially indicating an increase in particle size.
XPS was also used to determine estimated surface content of Au, Pd, C, O and Mg which is
displayed in Table 4. Although it was not possible to accurately determine the quantity of Pd
in the fresh AuPd/MgO sample, near stoichiometric quantities of Au and Pd were observed in
the used catalysts after reaction under H2 and N2. Interestingly, a significantly larger quantity
of oxygen is observed on the surface of the used catalysts, which provides further evidence
that the MgO undergoes partial hydroxylation during the reaction. It was previously
suggested that this is a result of H2O from the aldol condensation reaction taking place and is
supported by the diffraction data of the used catalysts displayed in Figure S3. Perhaps the
most significant finding from this technique is the larger quantities of carbon observed on the
surface of the used catalysts. This further supports the suggestion that catalytic deactivation
observed could be the result of coking on the surface of the catalysts during the reactions.
The deactivation mechanism of the catalyst still remains unclear. Although there is evidence
to suggest that the deactivation may be a consequence of particle agglomeration and/or
substrate coking on the catalysts surface. Enhancements and modifications in the design of
the catalyst that could alleviate these deactivation issues and allow for greater potential for
industrialisation of this process are needed.
Conclusion:
We report that AuPd nanoalloys supported on MgO and TiO2 are effective multi-functional
catalysts for the one-pot synthesis of 4-(4-methoxyphenyl)butan-2-one (4) from 4-

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methoxybenzyl alcohol (1) and acetone. This one-pot synthesis comprises dehydrogenation,
DOI: 10.1039/C7CY00184C
condensation and hydrogenation reactions. This is the first report of combining all these
reactions in one-pot. Throughout, we have portrayed this chemistry as a sequential
dehydrogenation-aldol-hydrogenation sequence. However, it can be viewed in another, very
general way as the overall alkylation of a ketone (acetone) by a benzyl alcohol 1. This places
the foregoing methodology in the same area as the recently developed protocols for achieving
the same overall transformations.28, 33, 34 Furthermore we have shown that the MgO supported
material is very active, as a heterogeneous catalyst, for the hydrogen auto transfer reaction.
Authors Contributions:
MM carried out initial catalytic experiments including catalyst preparation and testing under
the supervision of MS and this was followed by EN, MD, SI and HA under the supervision of
PM, GB and JKE. QH carried out the electron microscopy studies of the catalysts. DM was
involved in the XPS data acquisition and analysis. DWK and DB helped in the mechanistic
studies and data interpretation. MS initiated and supervised this project and GJH directed this
research program. All authors contributed to the manuscript preparation. PM designed the
graphical abstract.
Acknowledgement
M.M. thanks the Umm Al-Qura University, Saudi Arabia for his Ph.D. studentship and MS,
QH and JKE thank Cardiff University for their University Research Fellowships. Authors
thank the UK Catalysis Hub for resources and support provided via our membership of the
UK Catalysis Hub Consortium funded by the EPSRC (grants EP/K014706/2, EP/K014668/1,
EP/K014854/1, EP/K014714/1 and EP/M013219/1). Authors further thank the EPSRC for

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funding the ICP and MS equipment in the School of Chemistry, Cardiff University (grant
DOI: 10.1039/C7CY00184C
EP/L027240/1)
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DOI: 10.1039/C7CY00184C
Scheme 1. General scheme for the tandem synthesis of aldols from alcohol and ketone by
combining dehydrogenation, coupling and hydrogenation reactions.

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Table 1. Synthesis of 4-(4-methoxyphenyl)butan-2-one (4) from 4-methoxybenzyDlaOlI:c1o0.h10o3l9/C(17C)Y00184C
and acetone using supported metal bi-functional catalyst.
Catalyst
Conv Products
selectivity
(%)
(%)[a]
2
0
0
0
0
3
4
5
6
[b]
[c]
1%AuPd/TiO2
1%AuPd/TiO2
100
100
100
57
<1 27 14 57
0
0
55 21 24
55 11 34
[d]
1%Pd/TiO2
1%AuPd/MgO
44 32
1
<1
Reaction conditions: 4-methoxybenzyl alcohol: 1.3g; acetone: 6.3g; mesitylene (internal
standard): 1g; catalyst: 0.5g; pH2: 5 bar; T: 348K; time: 17h. Keys [a]: selectivity is
calculated based known and identified products and we have used a normalisation method
based on these products. The C balance for these reactions were calculated to be between 70-
80%. Remaining products are unidentified (20-30%); [b]: oxidative dehydrogenation for 3h
followed by reduction for 2h; [c]: oxidation for 3h followed by coupling reaction for 17h and
hydrogenation for 2h. [d]: oxidative dehydrogenation for 3h followed by coupling reaction
for 17h and hydrogenation for 3h.

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DOI: 10.1039/C7CY00184C
Table 2. Tandem synthesis using different alcohols and ketones with1%Au-Pd/MgO.
R1
R2
Atm Conv
(%)
Product selectivity
(%)[a]
2
3
4
5
6
OCH3
OCH3
H
CH3 N2
H2
96
100
79
97
65
65
34
90
1
55 43
85 10 5
14 73 12 0
0
4
0
0
C2H5 N2
H2
2
0
0
0
6
0
4
78 13 5
CH3 N2
H2
74 17
6
2
0
2
3
11
88
0
6
81
0
C(CH3) C2H5 N2
H2
6
95
3
Reaction conditions: 4-methoxybenzyl alcohol: 1.3g; benzyl alcohol: 1.1g, 4-tertbutyl benzyl
alcohol:1.54g, 2-butanone:7.7g acetone: 6.3g; mesitylene (internal standard): 1g; catalyst:
0.5g; p: 5 bar; T: 398K; time: 22h. [a]: selectivity is calculated based known and identified
products and we have used a normalisation method based on these products. The C balance
for these reactions were calculated to be between 70-80%. Remaining products are
unidentified (20-30%);

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DOI: 10.1039/C7CY00184C
Table 3. Reusability studies using 1 wt.% Au-Pd/MgO.
Atm
Conv
Product selectivity
(%)[a]
(%)
2
1
-
3
4
43
-
5
0
6
96
/
55
-
4
-
N2
-
100
46
0
0
0
85
77
10
16
5
H2
6
0.3
Reaction conditions: 4-methoxybenzyl alcohol: 1.3g, acetone: 6.3g; mesitylene (internal
standard): 1g; catalyst: 0.5g; p: 5 bar; T: 398K; time: 22h. [a]: selectivity is calculated
based known and identified products and we have used a normalisation method based on
these products. The C balance for these reactions were calculated to be between 70-80%.
Remaining products are unidentified (20-30%);

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DOI: 10.1039/C7CY00184C
Table 4. Atomic % of elements observed on the catalysts surface as determined by XPS of the
fresh 1 wt.% AuPd/MgO catalyst and after reactions under H2 and N2.
Atomic %
Catalyst
C
Mg
O
Au
Pd
AuPd MgO Fresh
AuPd MgO Used H2
AuPd MgO Used N2
5.84
46.58
47.4
0.19
n.d.
9.65
9.63
31.54
32.53
58.59
57.62
0.12
0.10
0.10
0.12

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DOI: 10.1039/C7CY00184C
(a)
(b)
(c)
Figure 1. Representative TEM images of Au-Pd/MgO catalysts prepared using nano-
Mg(OH)2 showing the Au-Pd nanoparticles on (a) the catalyst prior to reaction, (b) the used
catalyst after the reaction with 4-methoxybenzyl alcohol under H2 and (c) the used catalyst
after the reaction with 4-methoxybenzyl alcohol under N2.

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DOI: 10.1039/C7CY00184C
(a)
(b)
(c)
(d)
(a)
(b)
(c)
Figure 2. Representative TEM images of Au-Pd/MgO catalysts prepared using nano-
Mg(OH)2 showing the support structure change on the (a) AuPd/MgO catalyst prior to
reaction, and (b, c) the used AuPd/MgO catalyst after the reaction with 4-methoxybenzyl
alcohol under H2. The insets are corresponding select area electron diffractions. (d) shows
the rotational average of the diffraction pattern shown in (a), (b) and (c). ●: Mg(OH)2
brucite phase; ▲: MgO phase

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DOI: 10.1039/C7CY00184C

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DOI: 10.1039/C7CY00184C
Figure 3. Au(4f)/Mg(2s) and Pd(3d)/Mg(KLL) Auger peak photoemission spectra for (a)
AuPd/Mgo Fresh, (b) AuPd/MgO- N2 and (c) AuPd/MgO-H2.