Oxidations of allylic and benzylic alcohols under inductively-heated flow conditions with gold-doped superparamagnetic nanostructured particles as catalyst and oxygen as oxidant

Article abstract of DOI:10.1002/adsc.201400261

A continuous flow protocol for the oxidation of allylic and benzylic alcohols to aldehydes and ketones, respectively, using oxygen gas or atmospheric air is reported. The key features of this work are gold nanoparticles that are attached to the surface of nanostructured core shell particles composed of an Fe3O4-containing core and a silica shell. These nanostructured particles exert superparamagnetic properties and thus inductively heat up in an external oscillating electromagnetic field, conditions under which the gold catalyst is able to perform these oxidation reactions.

Full text of DOI:10.1002/adsc.201400261

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DOI: 10.1002/adsc.201400261
Oxidations of Allylic and Benzylic Alcohols under Inductively-
Heated Flow Conditions with Gold-Doped Superparamagnetic
Nanostructured Particles as Catalyst and Oxygen as Oxidant
Sangeeta Roy Chaudhuri,a Jan Hartwig,a Lukas Kupracz,a Torben Kodanek,b
Jens Wegner,a and Andreas Kirschninga,*
a
Institut fꢀr Organische Chemie und Zentrum fꢀr Biomolekulare Wirkstoffe (BMWZ), Leibniz Universitꢁt Hannover,
Schneiderberg 1B, 30167 Hannover, Germany
Fax : (+49)-(0)511-762-3011; phone: (+49)-(0)511-762-4614; e-mail: andreas.kirschning@oci.uni-hannover.de
Laboratorium fꢀr Nano- und Quantenengineering (LNQE), Leibniz Universitꢁt Hannover, Schneiderberg 39, 30167
b
Hannover, Germany
Received: March 13, 2014; Revised: July 23, 2014; Published online: October 16, 2014
Supporting information for this article is available on the WWW under http://dx.doi.org/10.1002/adsc.201400261.
Abstract: A continuous flow protocol for the oxida-
tion of allylic and benzylic alcohols to aldehydes
and ketones, respectively, using oxygen gas or at-
mospheric air is reported. The key features of this
work are gold nanoparticles that are attached to the
surface of nanostructured core shell particles com-
posed of an Fe3O4-containing core and a silica shell.
These nanostructured particles exert superparamag-
netic properties and thus inductively heat up in an
external oscillating electromagnetic field, conditions
under which the gold catalyst is able to perform
these oxidation reactions.
such oxidation processes.[11,12] These also include
metal-based nanoparticles (NPs) that are based on
Pd, Pt and Ag.[13] Gold nanoparticles (Au-NPs) have
recently found use in heterogeneous catalysis,[14] espe-
cially in oxidations of alcohols and nitrogen-contain-
ing compounds.[15] In this context they have been
found to exhibit better selectivities for multifunctional
alcohols compared to other metals, including al-
loys.[15d,16] Mechanistic studies by Corma and co-work-
ers identified several factors which are important for
the catalytic activity of gold nanoparticles.[16a,17] When
particles have dimensions below 10 nm, “naked”, re-
active gold atoms are present in large numbers at the
edges and corners of these particles. The active sites
show strong catalytic activity in oxidations.[18] The cat-
alytic performance of Au-NPs also depends on their
shape and on the supporting material used to con-
struct the nanoparticle.[19] In order to guarantee high
catalytic activity, stability and easy recovery, Au-NPs
Keywords: flow chemistry; gold; inductive heating;
nanostructures; oxidation; superparamagnetism
The oxidation of alcohols is one of the most impor- are generally dispersed on suitably chosen support
tant synthetic processes in academia and industry.[1] materials.
Common methods of oxidation utilize stoichiometric
In the past decade, magnetic nanoparticles have
oxidants based on chromium[2] or hypervalent iodine emerged as new supports for the generation of metal-
reagents.[3] Alternatively catalytic methods based on doped NPs with catalytic properties. The magnetic
tetra-n-butylammonium
perruthenate
(TPAP),[4] properties allow easy removal of the catalyst from the
stable N-oxyl radicals (TEMPO),[5–9] or zirconia[10] in reaction mixture. Other features of the particles
the presence of appropriate cooxidants have enjoyed which make them attractive are their easy preparation
widespread use. One of the major drawbacks of these and low toxicity.[20]
systems is the price of oxidants and cooxidants, and
Even though heterogeneous catalysts have been re-
the difficulty in the separation of the by-products ported to facilitate oxidation, there is a genuine con-
from the products. Other drawbacks are reduced cern that the process of mixing the catalyst, reactant
atom economy, as well as issues, concerning toxicity.
and gaseous oxidant can lead to explosive hazards,
Molecular oxygen is the cheapest and most user particularly if the reactions are performed batchwise
friendly oxidant, and as water is commonly formed, on a large scale.[21]
purification issues are of minor importance. Metal
In recent years, continuous flow processing has
catalysts have served to activate molecular oxygen in emerged as a powerful and safe enabling technolo-
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Oxidations of Allylic and Benzylic Alcohols
gy[22] that provides precise reaction control with re-
spect to mass and heat transfer as only a small portion
of the reaction mixture is exposed to the reaction con-
ditions. The possibility of rapid heating and cooling in
flow systems[23] reduces the risk of uncontrolled exo-
thermic reactions.[24] For example, flow devices make
it possible to carry out high temperature reactions
with sodium azide or hydroazoic acid.[25] Several
groups, including our own, have performed oxidation
reactions under flow conditions, utilizing a wide range
of reagents, including CrO2, NiO2, KMnO4, ozone,
DMSO/trifluoroacetic anhydride, NaOCl/catalytic
Bu4NBr, and immobilized versions of TEMPO and
ruthenium complexes.[26]
Over the past years, we have disclosed the first ap-
plications of ferromagnetic materials like steel beads,
copper metal and superparamagnetic nanostructured
particles as heating media in chemical synthesis under Scheme 1. Preparation of nanostructured, gold-doped parti-
cles 4 (MAGSILICAꢃ).
flow conditions.[27] These studies also included the
synthesis of the clinical drugs olanzapine and amitryp-
tilin.[28] We showed that many endothermic reactions,
such as transesterifications, condensations, Pd-cata- followed by metal reduction under forming gas at
lyzed cross-coupling reactions, and Wittig olefinations 4008C and further reduction in an autoclave under
can be conducted continuously using inductive heat- a hydrogen atmosphere to furnish the desired gold-
ing.[27]
doped core-shell particle 4 (Scheme 1). We prepared
Here, we report on the development of a catalytic two different types of particles that differed in the
flow process for the oxidation of alcohols using mo- amount of HAuCl4 employed during immobilization
lecular oxygen as the stoichiometric oxidant. Our pro- (2!3). Catalysts 4a and 4b differed in the amount
cess relies on catalytically active gold nanoparticles 4 and size of gold nanoparticles present on the silica
that are immobilized on nanostructured core shell surface. We used nanostructured, superparamagnetic
particles based on iron oxide (primarily Fe3O4) and nanoparticles 1 as supporting material,[31] composed
a silica shell. This complex particle architecture serves of an Fe3O4-containing core and an SiO2 shell.[32]
as fixed bed material in mesofluidic devices which can These particles were functionalized by coupling of (3-
be heated inductively (IH) in an external oscillating aminopropyl)trimethoxysilane (APTMS) to the silica
field due to the superparamagnetic properties of the coating. The basic amino groups in 2 facilitated load-
ꢀ
iron oxide core.
ing of the anionic Au complex [Au(OH)xCl4ꢀx
]
to
Preparation and characterization of catalytic yield 3. In our hands this protocol was superior to the
nanostructured particles: The most common methods adsorption of gold on SiO2 surfaces.[33] From X-ray
for attaching gold nanoparticles (Au-NPs) to a support absorption near edge structure analysis, Rossi et al.
are either by deposition–precipitation or by co-precip- concluded that amino groups grafted on solid sup-
itation.[29] Particle size and size distribution, as well as ports interact more strongly with metal ions than gold
degree of distribution on the support depend on the that is simply adsorbed on the surface of non-func-
pH, concentration, isoelectric point, the nature of the tionalized supports.[20b]
oxide support and the calcination temperature.[30]
The functionalization of MAGSILICAꢃ 1 with an
In the present work, we relied on the uptake of organic linker and amino groups was confirmed for
Au3+ ions from an aqueous HAuCl4 solution onto nanostructured particles 2, as well as, the Au-NPs 4,
amino-functionalized, silica-coated nanostructured by utilizing combustion analysis (Table 1). Clearly, the
magnetic particles 2. The loading was achieved at aminoalkyl functionalization resulted in an increase
pH 6 and yielded nanostructured particles 3. This was of carbon and nitrogen on MAGSILICAꢃ (entries 1
Table 1. Combustion analysis of non-funtionalized and functionalized supports 1, 2 as well as Au-NP (4).
Entry
Catalyst
C [%]
H [%]
N [%]
1
2
3
non-functionalized MAGSILICAꢃ
1
0.072
1.424
0.576
0.401
0.550
0.175
0.126
0.486
0.188
functionalized MAGSILICAꢃ 2
Au-NPs on MAGSILICAꢃ
4
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Sangeeta Roy Chaudhuri et al.
Figure 1. XRD image of Au-NP sample 4b (vertical lines in-
dicate signals that are characteristic for gold; signals with
strong intensities refer to Fe2O3 and Fe3O4, respectively).
and 2). The reduced carbon and nitrogen contents
(entry 3) of 4 can be ascribed to thermolysis of the
linker system in 3.
Figure 2. TEM measurements of catalyst samples 4a (a and
c) and 4b (b and d) and distribution of Au particle size (e:
Next, the crystalline properties and the presence of
gold on modified MAGSILICAꢃ 4 were confirmed by for sample 4a and f: for sample 4b).
X-ray diffraction (XRD) measurements and are
based on the appearance of diagnostic peaks at 2q
values 38.18, 44.39, 64.58 and 77.55 (Figure 1). How- for the presence of Au in catalytic samples 4a and 4b
ever, the broadening and the intensity of these peaks was collected by atomic absorption analysis (ICP
with respect to the iron peaks suggest low concentra- OES). These analyses revealed that catalyst sample
tion and a smaller average size of gold particles com- 4a contained 1.20 wt% gold while sample 4b had
pared to the core iron nanoparticles. It is noteworthy a loading of 2.76%.
that XRD analysis also revealed the presence of both
a hematite and magnetite phase.
Catalytic activity of Au-NP: The heating proper-
ties of gold-doped MAGSILICAꢃ 4a and 4b in an ex-
Next, the morphology of Au-NPs 4 was examined ternal oscillating electromagnetic field (medium fre-
with respect to varying concentrations of gold using quency=25 kHz) are similar to those of non-function-
electron microscopy and high resolution transmission alized, nanostructured particles 1 as shown for the
electron microscopy (TEM) (Figure 2a and b for cata- heating profiles (Figure 3).
lyst 4a and Figure 2c and d for catalyst 4b). No
Initially, we tested the catalytic activity of our com-
changes in the morphology of these nanoparticles plex nanostructured particles under batch conditions
were observed after modification of non-functional- in a sealed microwave vial. A suspension of 4-bromo-
ized MAGSILICAꢃ 1 and generation of immobilized benzyl alcohol and catalyst 4a in benzene was heated
Au-NPs 4, as deduced from the TEM images (see also under an oxygen atmosphere (5 bar) to 1508C using
the Supporting Information; Figures S1 and S2). The an external oil bath. After 6 h the degree of conver-
average diameter of Au-NPs on MAGSILICAꢃ was sion was low (13%). We then tested the oxidation
determined to be about 2.5 nm with a polydispersity under flow conditions employing a biphasic gas/liquid
of 41% for catalyst 4a and 5.8 nm with a polydispersity set-up.[34] Both nanoparticle samples 4a and 4b were
of 27% for catalyst 4b (Figure 2e and f). The average first probed with the same model alcohol, 4-bromo-
sizes of Au-NP were well below 10 nm.
benzyl alcohol, which gave aldehyde 5d (R1 =4-
The initial use of a larger amount of HAuCl4 BrC6H4, R2 =H; see also Table 4) with 75% conver-
during the immobilization step subsequently led to sion.
Au-NPs on MAGSILICAꢃ that are distinctly larger in
The flow set-up for the catalytic oxidations is
size (4b vs. 4a). In both cases, the Au-NPs are well shown in Scheme 2. Our previously reported PEEK
distributed across the surface of the support as shown (polyether ether ketone) reactor (14 cm length, 9 mm
in the histograms (Figure 2e and f). However, the par- internal diameter) was filled with a mixture of 0.5 g
ticle size distribution is narrower for catalyst sample (~6.0 or 13.8 mg Au) of catalyst 4a or 4b, respectively,
4a compared to catalyst sample 4b). Additional proof and 2.5 g MAGSILICAꢃ (total loading ~3 g) to facili-
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Table 2. Optimization of temperature (set-up see Scheme 2).
Entry[a]
Temp. [8C]
4-Br-BnOH [%]
Product [%]
1
2
3
4
5
52
70
100
113
150
99
98
78
46
3
1
2
22
54
97
[a]
Reaction conditions: 4-bromobenzyl alcohol (50 mg,
0.27 mmol) in benzene (3 mL), catalyst 4a (0.5 g, 6.0 mg
Au) and MAGSILICAꢃ (2.5 g), flow rate 0.05 mLminꢀ1.
O2 [p(O2)=7 bar].
[b]
Table 3. Optimization of flow rate (set-up see Scheme 2).
Entry[a,d]
Flow rate [mLminꢀ1]
Conversion [%]
1[b]
2[b]
3[b]
4[b]
5[c]
6[c]
0.05
0.1
0.2
0.3
0.1
0.3
100
100
98
52
100
63
[a]
Reaction conditions: 4-bromobenzyl alcohol (50 mg,
0.27 mmol) in benzene (3 mL).
Catalyst 4a (0.5 g, 6.0 mg Au).
Figure 3. Heating profiles of MAGSILICAꢃ 1 and Au-NPs
4a and 4b at 25 kHz.
[b]
[c]
Catalyst 4b (0.5 g, 13.8 mg Au), 1508C and MAGSILI-
CAꢃ (2.5 g).
[d]
O2 [p(O2)=7 (bar)].
heated catalytic reactor and was run with oxygen at
7 bar.
First, we optimized the reaction temperature and
the flow rate for the model oxidation using catalyst
sample 4a. Technically, it is extremely difficult to
measure the temperature of an inductively heated
nanoparticle inside the reactor. Therefore, we mea-
sured the temperature externally using an IR pyrome-
ter, being aware of the fact that the surface tempera-
ture of the reactor is lower than the actual tempera-
ture of the nanoparticle surface. The temperature was
adjusted with the power input of the AC-generator.
Scheme 2. Flow set-up for oxygen-promoted oxidations of
alcohols (the optimization was conducted for R1 =4-Br-C6H4
and R2 =H, see Table 2 and Table 3). MS=MAGSILICAꢃ.
tate inductive heating. This catalytic reactor was in- At 1008C 22% of 4-bromobenzyl alcohol was convert-
cased in an inductor suitable for medium frequency ed into aldehyde 5d (Table 2, entry 4). Complete con-
induction (25 kHz). Among many known multiphasic version was achieved by increasing the temperature
reactors such as segmented flow microreactors, to 1508C (entry 5). It is noteworthy that we and
packed-bed microreactors and falling film microreac- others[37] have encountered partial overoxidation to
tors,[34,35] we chose Leyꢄs tube-in-tube reactor.[28b,26c,36] the corresponding benzoic acids under batch condi-
Its design is well suited for introducing a gas into tions[38] but not for the flow set-up.
a stream of reactants. The reactor consists of a Teflon
Next, the degree of conversion with respect to resi-
AF-2400 tubing (0.8 mm AD, 0.6 mm ID) as a contact dence time was studied at 1508C by altering the flow
interface to saturate the liquid stream with rate. Complete conversion was achieved at flow rates
gas.[28b,26c,35] Teflon AF-2400 is an amorphous fluoro- between 0.05 and 0.1 mLminꢀ1 in all cases (Table 3,
polymer tubing which is highly permeable to gases entries 1 and 2) with a single pass of the reactor. A
but impervious to organic solvents.[36] The tube-in- flow rate of 0.2 mLminꢀ1 or 0.3 mLminꢀ1 led to in-
tube reactor was installed in front of the inductively complete conversion (entries 1 and 2). Oxidation of 4-
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Table 4. Oxidations of primary and secondary alcohols.[a]
bromobenzyl alcohol was carried out with catalyst 4b
under the same optimized conditions as described for
catalyst 4a. It is noteworthy that both nanocatalysts
4a and 4b behaved similarly at a lower flow rate of
0.1 mLminꢀ1 (compare entries 2 and 5). As we ex-
pected, the larger amount of Au nanoparticles present
in catalyst sample 4b furnished slightly better conver-
sions at higher flow rates (compare entries 4 and 6).
Besides benzene we also tested methanol, ethyl
acetate, acetonitrile and dichloromethane as solvents
Entry
Product
Conversion Yield
[%][b]
[%][c]
R=H
(5a)
1[d]
2[d]
100
100
98
85
R=Me
(5b)
R=Cl
(5c)
R=Br
(5d)
3[d]
100
100
93
but in no case did we observe full conversion. Al- 4[d]
though in toluene full conversion was achieved, we
94 (18)
63
5[e]
R=NO2 70
also had to encounter the formation of by-products
that derive from the oxidation of toluene, which ham-
pered work-up. With the optimized conditions in
hand, we expanded our flow protocol to other alco-
hols (Table 4). These oxidations commonly proceeded
with complete conversions and good to very good iso-
(5e)
R=OMe 100
(5f)
6[d]
65
7[e]
100
75[d]
lated yields were obtained (Table 4) (residence times
30–60 min). Primary benzyl alcohols and allylic alco-
hols were selectively converted to the corresponding
aldehydes 5a–5i under these flow conditions without
8[d]
100
100
90
formation of undesired side reactions such as overoxi-
9[d]
85 (8)
dation. The presence of electron-withdrawing groups
(entries 5 and 7) leads to decreased reaction rates.
Better conversion was achieved at a lower flow rate
of 0.05 mLminꢀ1 as exemplified for the preparation of
salicyl aldehyde 5g (entry 7). However, this continu-
ous oxidation protocol is not suited when substrates
or products are thermally unstable such as furfuryl al-
cohol.
10[d]
100
100
90 (10)
83
11[e]
[a]
The oxidation of secondary alcohols such as diphe-
nylmethanol and 1-phenylpropan-1-ol to the corre-
sponding ketones 5j–5k also proceeded smoothly (en-
tries 10 and 11). In selected cases (entries 4, 9 and 10)
we performed the oxidation in the absence of the
gold nanoparticles using non-functionalized MAG-
SILICAꢃ 1 as fixed bed material under the same con-
ditions. Formation of only small amounts of oxidation
Reaction conditions: alcohol (0.27 mmol) in benzene
(3 mL), catalyst 4b (0.5 g, 13.8 mg Au), 1508C and MAG-
SILICAꢃ (2.5 g).
[b]
[c]
O2 [p(O2)=7 (bar)].
Isolated yields; values in brackets refer to yields in the
presence of non-functionalized MAGSILICAꢃ and the
absence of Au-NPs.
[d]
[e]
Flow rate=0.1 mLminꢀ1.
Flow rate=0.05 mLminꢀ1.
1
products was observed as judged by H NMR spec-
troscopy.
In selected cases, we observed that the acidic char-
acter of the silica shell in 4 is able to promote elimi-
nation of water, a process that can overrule oxidation
(Scheme 3). This was observed for 1-(2-methoxynaph-
thalen-6-yl)ethanol (6) that provided the desired
ketone 5l as a by-product along with styrene deriva-
tive 7. In the case of 1,2,3,4-tetrahydronaphthalen-1-
ol (8) only naphthalene (9) was formed which likely
resulted from water elimination followed by oxidative
aromatization.
Indeed, MAGSILICAꢃ 1 is able to promote water
elimination, as demonstrated in the case of cyclohexa-
nol (10) (Table 5). When carbinol 10 and 1 were
heated in an oil bath for 6 h, cyclohexene 7 was
formed in 2% yield. When the system was subjected
to the same conditions but heated by an external os- Scheme 3. Water eliminations as side reactions.
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Oxidations of Allylic and Benzylic Alcohols
Table 5. Studies on water elimination under thermal conditions using MAGSILICAꢃ 1.
Entry
Heating mode
Conditions[a]
Yield 3 [%][b]
1
2
3
4
oil bath
1508C,6 h (batch)
2
IH (medium frequency)
IH (high frequency)
IH (medium frequency)
25 kHz, 1108C, 6 h (batch)
800 kHz, 1308C,[c] 2 h (batch)
25 kHz, 1208C,[c] 0.03 mLminꢀ1 (flow)
12
99
98
[a]
Reaction conditions: cyclohexanol (300 mg, 30.0 mmol) and MAGSILICAꢃ (300 mg) in a closed vial; the oil bath temper-
ature was measured by a temperature sensor; IH induced temperature was determined by an IR pyrometer.
Calculated from the 1H NMR spectrum.
[b]
[c]
Temperature adjusted by inductor power input.
cillating electromagnetic field (25 kHz, medium fre-
We noted slow deactivation[39] of the catalyst after
quency) 7 was formed in yields of 12%. When high- 35–40 separate oxidations with the same flow system.
frequency conditions (800 kHz) were employed, The two catalysts 4a and 4b show TONs of minimum
almost complete conversion was encountered at 350 and 154, respectively. Several factors can be re-
1308C within in a shorter time. This observation also sponsible for the deactivation, one being leaching of
occurred under flow conditions in a medium-frequen- the gold nanoparticles. To get further insight, we col-
cy field (entry 4).
lected product samples in regular intervals at the
We next aimed to carry out a scale-up study to outlet of the flow system during the oxidation of pyri-
demonstrate the practicability of this catalytic system. dine-3-ylmethanol to nicotine aldehyde 5h (table 4,
Therefore, a PEEK reactor was filled with 2.0 g of entry 8). The reactor contained 500 mg of catalyst
catalyst 4a (24.0 mg Au) and 1.0 g of MAGSILICAꢃ sample 4b (13.8 mg Au). These samples were analyzed
1. Thus, 4-bromobenzyl alcohol (2.5 g 13.37 mmol) by ICP OES (Figure 4). Leaching of gold reached
was dissolved in 50 mL benzene and the solution was a maximum after about 4 h before it went back to
pumped through the reactor at a flow rate of values below 2 ngmLꢀ1. After 12 h of continuous syn-
0.1 mLminꢀ1. Several reaction parameters were thesis of nicotine aldehyde 5h we encountered no de-
changed towards higher productivity The concentra- activation of the flow system.
tion of the reaction mixture was increased three-fold
We ascribe the unexpected peak of Au leaching (up
and the flow rate was doubled while catalyst loading to 22 ngmLꢀ1; 3–6 h) to unbound or weakly absorbed
was only increased by a factor of four. The desired gold that leaves the reactor under the force of the
product was isolated in 92% yield. The same transfor- convective flow. The total amount of gold leached
mation was repeated using pressured air instead of from the samples is negligible (the total amount of
oxygen gas. Gratifyingly, the catalyst also showed
high activity with atmospheric oxygen as oxidant and
the product was isolated in 96% yield (Scheme 4).
Scheme 4. Oxidation of 4-bromobenzyl alcohol with atmos-
pheric oxygen as oxidant. Reaction conditions (i): 4-bromo-
benzyl alcohol (100 mg, 0.54 mmol) in benzene (4 mL); reac-
tion conditions (ii): catalyst 4a (2.0 g, 24.0 mg Au), 1508C
and MAGSILICAꢃ (1.0 g).
Figure 4. Leaching of gold (from two independent measure-
ments) from catalyst sample 4b as determined by ICP QMS
(for test reaction refer to Table 4, entry 8; conditions men-
tioned there apply); accumulative presentation (dark grey
graph), leaching of hourly taken samples (light grey bars).
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gold collected was 202.3 ng, 0.00147%, compared to potential applications for continuous oxygen-promot-
13.8 mg Au in the reactor fixed bed).
ed oxidations in technical processes.
A second factor is the chemical stability of the
silica support and the nanostructured particles under
the reaction conditions. In order to address this issue Experimental Section
TEM micrographs of the used catalyst 4b were taken
(see Figure S3 in the Supporting Information). These Synthesis of Gold Nanoparticles
distinctively differed from the freshly prepared cata-
Catalyst 4a: HAuCl4·3H2O (20 mg, 0.05 mmol) was dis-
lyst samples 4a and 4b shown in Figure 2. However,
the morphology of the silica support (Fe3O4@SiO2)
had not changed during catalysis and had stayed
intact. However, we found that very small gold nano-
particles were absent on the support. The difficulty to
find gold particles can in part be accounted for by the
fact that the catalytic fixed bed material was com-
posed of a mixture of MAGSILICAꢃ 1 (2.5 g) and
catalysts sample 4 (500 mg) which led to dilution of 4.
Secondly, the gold particles underwent aggregation
during the catalytic process, forming larger and less
active particles. This may also lead to reduced reactiv-
ity over prolonged reaction times.
In order to exclude the possibility of a homogeneous
reaction catalyzed by gold present in solution
a PEEK reactor was filled with untreated MAGSILI-
CAꢃ 1 (~3.0 g). The reaction was carried out with
a solution of 100 mg 4-bromobenzyl alcohol and
200 ng HAuCl4 (50 ngmLꢀ1 Au) in 2.0 mL benzene
under standard conditions. After the reaction 90%
starting material was recovered via flash chromatog-
raphy while slight decomposition and no significant
product were observed.
solved in double distilled water (500 mL, 0.1 mM in
HAuCl4). The pH of the solution was set to 6 with dropwise
addition of 0.2M NaOH. Functionalized MAGSILICAꢃ-
NH2 2 (1 g) was added to the reaction and the suspension
was stirred for 24 h at room temperature. The nanostruc-
tured particle was then fixed with an external magnet and
the suspended liquid was decanted. The particles were
washed three times with double distilled water and dried
under vacuum at 608C for 16 h. The particles were then re-
duced for 3 h at 4008C in tube furnace under forming gas
(97/3; 7 Lhꢀ1) and subsequently reduced in autoclave for
16 h at 808C and 10 bar H2 in cyclohexane.
General Procedure for Oxidations under Flow
Conditions
A PEEK reactor was filled with a mixture of gold nanopar-
ticles (500 mg) and MAGSILICAꢃ (~2.5 g) and encased
with the inductor. The reactor (void volume: 3 mL) was con-
nected to the tube-in-tube reactor, which was run with O2 at
7 bar, a pump and at the outlet with a back-pressure device
(250 psi), which then led to the collecting vial. The flow
device was flushed with benzene, and the temperature was
adjusted to 1508C. Once a constant temperature of the
stream (flow rate 0.05 or 0.1 mLminꢀ1) was reached, a solu-
tion of the alcohol dissolved in benzene was pumped
through the system (residence time ca. 30–60 min). The re-
action mixture was collected, and after removal of the sol-
vent under reduced pressure, the crude product was purified
by column chromatography (silica gel) to yield the corre-
sponding aldehyde or ketone, respectively.
In conclusion, we report on the design of nano-
structured core shell particles based on iron oxide
(primarily Fe3O4) and a silica shell that are doped
with gold nanoparticles (<10 nm).[40] This nanostruc-
tured architecture allows rapid heating in direct prox-
imity of the heterogenic, catalytically active gold
nanoparticles under inductive heating conditions and
their use in O2-promoted oxidations of allylic and
benzylic alcohols primary and secondary alcohols, Acknowledgements
which provided aldehydes and ketones, respectively.
S. R. C. and J. W contributed equally to this work. This re-
The catalytic samples were mixed with nanostruc-
tured core-shell iron oxide and used as catalytic fixed
bed materials in mesofluidic PEEK reactors. The pro-
cesses were conducted under high pressure/high tem-
perature conditions and provided in almost all cases
complete conversion in a single pass. The catalytically
active nanoparticles show excellent distribution across
the nanostructured surface of the core shell nanopar-
ticles with sizes below 10 nm and low polydispersity.
Catalyst leaching is negligible with less than 0.0015%
over 12 h of operation. The high activity of the cata-
lyst was demonstrated after upscaling as well as when
exchanging oxygen gas by atmospheric oxygen as oxi-
dant. It is important to note that no overoxidation oc-
curred during the flow-process. We are certain that
the catalyst architecture and the technical set-up has
search was supported in part by the Fonds der Chemischen
Industrie (Ph. D. scholarship for J. H.) and by Henkel AG &
Co. KGaA (Dꢀsseldorf, Germany). We thank H. Herzog and
Prof. S. Katusic (EVONIK Industries AG, Essen, Germany)
for technical support. TEM measurements were conducted at
the Laboratory of nano- and quantum engineering (LNQE,
Leibniz University Hannover). We are grateful to Dr. M.
Wiebcke and J. Thieleke (both institute of inorganic and ana-
lytical chemistry, Leibniz University Hannover) for XRD
analyses and ICP-OES measurements, respectively. We thank
the referees for providing helpful suggestions.
3536
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Adv. Synth. Catal. 2014, 356, 3530 – 3538

COMMUNICATIONS
Oxidations of Allylic and Benzylic Alcohols
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3538
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Adv. Synth. Catal. 2014, 356, 3530 – 3538