Menthylamine synthesis via gold-catalyzed hydrogenation of menthone oxime

Article abstract of DOI:10.1016/j.apcata.2020.117799

In the current work gold nanoparticles supported on oxides (MgO, Al₂O₃, ZrO₂, TiO₂) were used for menthylamine synthesis via menthone oxime hydrogenation. An increase of the gold nanoparticles size and application of metal oxides with a strong basic character such as magnesia favored deoximation to menthone. Au/Al₂O₃ catalyst with the gold nanoparticles size of 2.0 nm afforded high catalytic activity and selectivity to menthylamine. The reaction kinetics including stereoselectivity to the reaction products and recyclability of the catalyst was studied using Au/Al₂O₃ in the temperature range 90?110 °C under hydrogen pressure of 5.5–7.5 bar. The catalytic behavior was influenced by the solvent nature, with higher selectivity to desired amine achieved using methanol. The reaction rate was pressure independent, while has first order with respect to menthone oxime concentration. Stereoselectivity to menthylamines and menthones was independent on the reaction temperature and the hydrogen pressure.

Full text of DOI:10.1016/j.apcata.2020.117799

Applied Catalysis A, General 605 (2020) 117799
Contents lists available at ScienceDirect
Applied Catalysis A, General
journal homepage: www.elsevier.com/locate/apcata
Menthylamine synthesis via gold-catalyzed hydrogenation of menthone
oxime
Yu.S. Demidova , E.S. Mozhaitsev , E.V. Suslov , A.A. Nefedov , A.A. Saraeva,b, K.P. Volchob,c,
a,b
c
d
c
b,c
b,c
a,
e
N.F. Salakhutdinov , A. Simakov , I.L. Simakova *, D.Yu. Murzin
a
b
c
d
Boreskov Institute of Catalysis, pr. Lavrentieva 5, 630090, Novosibirsk, Russia
Novosibirsk State University, Pirogova 2, 630090, Novosibirsk, Russia
Novosibirsk Institute of Organic Chemistry, pr. Lavrentieva 9, 630090, Novosibirsk, Russia
Universidad Nacional Autónoma de México, Centro de Nanociencias y Nanotecnología, km. 107 carretera Tijuana a Ensenada, C.P. 22860, Ensenada, Baja California,
Mexico
e
Process Chemistry Centre, Åbo Akademi University, FI-20500, Turku/Åbo, Finland
A R T I C L E I N F O
A B S T R A C T
Keywords:
In the current work gold nanoparticles supported on oxides (MgO, Al
2
O
3
, ZrO
2
, TiO ) were used for menthy-
2
Oxime hydrogenation
Terpenoids
lamine synthesis via menthone oxime hydrogenation. An increase of the gold nanoparticles size and application
of metal oxides with a strong basic character such as magnesia favored deoximation to menthone. Au/Al
O
2 3
Menthylamine
Gold catalyst
Biomass
catalyst with the gold nanoparticles size of 2.0 nm afforded high catalytic activity and selectivity to menthy-
lamine. The reaction kinetics including stereoselectivity to the reaction products and recyclability of the catalyst
was studied using Au/Al
2
O in the temperature range 90−110 °C under hydrogen pressure of 5.5–7.5 bar. The
3
Kinetics
catalytic behavior was influenced by the solvent nature, with higher selectivity to desired amine achieved using
methanol. The reaction rate was pressure independent, while has first order with respect to menthone oxime
concentration. Stereoselectivity to menthylamines and menthones was independent on the reaction temperature
and the hydrogen pressure.
1
. Introduction
Stereo-, regio- and chemoselective hydrogenation is of interest for
menthylamine [4] (Fig. 1), which is of great practical interest due to its
wide application for synthesis of catalysts for chiral phase-transfer [5]
and a range of chiral reactions, including hydrosilylation [6–8], Mi-
chael addition [9,10], asymmetric epoxidation [11,12]and Henry re-
actions [13]. Moreover, menthylamine is applied for synthesis of the
stationary phase for high performance column chromatography [14].
Based on menthylamine, some biologically active compounds were
obtained, including selective antagonists of TRPM8 channels, an im-
portant target for neuropathic analgesic drugs [15], as well as an-
tagonists/inverse agonists of cannabinoid CB2 receptors [16].
synthesis of the desired products with a high efficiency. Widespread
terpenoids form the largest group of natural compounds and are ex-
tensively applied as platform molecules in food, pharmaceutical and
perfumery industries [1]. Terpenoids often contain asymmetric centers
and several functional groups, including reducible ones. Development
of selective catalysts for reduction of different functional groups in
terpenoids aiming at production of valuable intermediates for fine
chemicals and pharmaceuticals is a challenging task. Hydrogenation of
monoterpene oximes is one of the key steps in the synthesis of valuable
compounds. There is a variety of products that can be obtained starting
from oximes including carbonyl compounds and amines. For instance,
deoximation of carvone oxime is a key step in the synthesis of in-
dustrially valuable carvone from limonene [2]. Different terpene
oximes are widely used as starting compounds and intermediates to
obtain important heterocycles, nitriles, amines and carbonyl com-
pounds [3]. Reduction of menthone oxime leads to formation of
Menthylamine can be produced from menthone via a multistep re-
ductive amination under Leuckart–Wallach conditions (a thermally
driven reaction) or from menthone oxime under Bouveault–Blanc
conditions using absolute ethanol and sodium metal and via hydro-
genation using a transition metal catalyst [4,17,18]. In particular,
menthone oxime was reduced using platinum black in glacial acetic
acid and Raney nickel in methanol [4,18]. These approaches resulted in
menthylamine formation as a diastereomeric mixture, with the total
yield of amine reaching 40–60 %. The reaction complexity is related to
⁎
Corresponding author.
E-mail address: simakova@catalysis.ru (I.L. Simakova).
https://doi.org/10.1016/j.apcata.2020.117799
Received 19 May 2020; Received in revised form 18 August 2020; Accepted 19 August 2020
Available online 21 August 2020
0926-860X/ © 2020 Elsevier B.V. All rights reserved.

Y.S. Demidova, et al.
Applied Catalysis A, General 605 (2020) 117799
Generally, utilization of gold catalysts with low hydrogenation ac-
tivity did often provide higher chemoselectivity compared to conven-
tional hydrogenation over Pt, Pd, Ru catalysts in the case of compli-
cated substrates with several reducible functional group, such as
terpenoids [36,37]. Herein the research program of the authors on
terpene oximes hydrogenation over heterogeneous metal catalysts was
further expanded. In the present work the focus was on the gold catalyst
design for direct menthone oxime hydrogenation to menthylamine
(
Fig. 1), a compound of a high practical value. To the best of our
knowledge, gold catalysts have never been applied for a systematic
study of chemoselective oxime hydrogenation. Menthone oxime with a
relatively simple structure was selected aiming at further application of
the designed catalyst and approaches for more complicated structures
of monoterpene oximes, containing reducible functional groups. As
expected, Au catalysts can provide higher chemoselectivity compared
to conventional Pt catalysts and were successfully applied for selective
menthone oxime hydrogenation to menthylamine in the previous work
of the authors [19]. On the other hand, it should be noted that men-
thylamine has three stereocenters resulting in diastereomers formation.
A detailed study of mechanistic and kinetics regularities, including
dynamics of diastereomers formation, was thus performed with gold
containing catalysts.
Fig. 1. Scheme of gold-catalyzed transformation of menthone oxime under
hydrogen atmosphere.
possible formation of four diastereoisomers, namely, neomenthylamine,
menthylamine, isomenthylamine and neoisomenthylamine. In our re-
cent work Pt catalysts based on metal oxides were successfully used for
menthone oxime hydrogenation to menthylamine [19]. Menthone
2. Experimental/methodology
oxime hydrogenation over Pt/Al
2
O
3
catalysts provided the desired
2.1. Preparation of catalysts
amine formation with the selectivity of 90 % at complete oxime con-
version. At the same time Pt catalysts application for hydrogenation of
oximes, containing several reducible functional groups, such as carvone
oxime, led to non-selective hydrogenation of both C]C and C]N bond
Gold catalysts comprising Au (2 wt.%) on metal oxides were pre-
pared by the deposition-precipitation method [38]. Commercial Al
2 3
O
(Sasol), ZrO
2
(Alfa-Aesar), TiO (Degussa AG, Aerolyst 7708), and MgO
2
[
19].
(Vekton) oxides were used as supports. The measured BET surface areas
As potential catalysts for selective hydrogenation of oximes to
amines gold nanoparticles supported on metal oxides can be also con-
are presented in Table 1. Typically, an aqueous solution of HAuCl
4
−3
(1.6 × 10
M) and urea (0.21 M) was heated up to 81 °C and the
sidered. Previously it has been demonstrated in our work that Au/TiO
2
supports in the powder form (< 63 μm) were added. The slurry was
mixed for 4 h at 81 °C and then filtered and washed with water. Ad-
ditionally, in the case of titania a different concentration of the gold
catalyst promoted a one-pot synthesis of dihydrocarvone comprising
sequential transformations of carvone oxime to dihydrocarvone [20],
which is widely used as a flavoring additive in food industry [21]. In
−4
precursor (5 × 10 M) and duration of the deposition of 24 h instead
of 4 h were applied to vary the gold nanoparticles size. An excess of
chloride in the samples after gold deposition was removed by washing
that work, application of Au/TiO catalyst for both deoximation and
2
selective hydrogenation of conjugated olefinic C]C functional group
was reported for the first time. Note, that unconjugated C]C double
bond remained intact. A significant increase in stereoselectivity towards
trans-dihydrocarvone was observed when carvone oxime was hydro-
genated: the ratio between trans- and cis-dihydrocarvone was close to
with a solution of NH OH, as reported in [38,39]. Thereafter the cat-
4
alysts were washed thoroughly with deionized water, filtered and dried
at room temperature for 24 h. Before the catalytic tests, the samples
were pre-treated in air flow increasing temperature to 350 °C with a
ramp rate of 2 °C/min.
4
.0 compared to 1.8 achieved in carvone hydrogenation [2,22]. How-
ever, no amine formation was detected in that work. Generally gold
catalysts showed outstanding selectivity and activity in the hydrogen
borrowing reactions, as well as in hydrogenation of aldehydes, olefins
2.2. Characterization of supports and catalysts
[
23–29]. They are well known as catalysts of the choice for chemose-
The fresh catalysts were studied by X-ray fluorescence spectroscopy
lective hydrogenation of nitro compounds in the presence of reducible
functional groups [30–34]. Hydrogenation of nitrocompounds to
amines was shown to proceed via an intermediate hydroxylamine de-
rivative formation, while Corma et al. obtained oxime from α,β-un-
(
XRF), nitrogen adsorption technique, transmission electron micro-
scopy (TEM), and X-ray photoelectron spectroscopy (XPS).
The gold content in the synthesized catalysts was analyzed with an
XRF with the powder pellet method using an ARL PERFORM’X spec-
trometer equipped with a rhodium anode X-ray tube (Thermo Fisher
Scientific, USA). The porous structure of the catalysts was evaluated by
saturated nitrocompounds with H using a gold catalyst [31,32]. Wang
2
et al. reported gas phase hydrogenation of nitrocyclohexane over sup-
ported gold catalysts with the oxime being detected among the reaction
products [35]. A cooperative effect between the metal and the support
N adsorption in a Micromeritics TriStar II-3020 device (Micromeritics
2
Instrument Corp., USA). Prior the analysis, the samples were degassed
to dissociate H and to adsorb the substrate was revealed [33]. It was
2
discussed by Boronat et al. that the desired selectivity can be achieved
by using a proper support for the nitro group adsorption on the support
and at the gold-support interface [33]. Shimizu et al. proposed co-
operation of the acid-base pair site on alumina and the coordinatively
unsaturated Au atoms on Au nanoparticles for heterolytic molecular
Table 1
Specific surface area and pores of oxides used as supports.
2
3
Sample
S
BET, m /g
Pore volume, cm /g
Pore diameter, nm
MgO
Al O
33
0.2
0.5
0.3
0.2
22.6
10.3
10.8
7.6
+
−
hydrogen dissociation to H /H pair at the metal/support interface
204
103
45
2
3
[
32]. Following the latter study utilization of metal oxides containing
ZrO
2
TiO
2
both acid and basic active sites is preferable.
2

Y.S. Demidova, et al.
Applied Catalysis A, General 605 (2020) 117799
in vacuum at 300 °C for 4 h using a Micromeritics VacPrep 061-Sample
degas system (Micromeritics Instrument Corp., USA). The specific sur-
face areas of the catalysts were determined with the Brunauer-Emmett-
Teller (BET) method, while the pore size distribution was determined
by the BJH model.
HP-5 MS column (length 30 m, inner diameter 0.25 mm and film
thickness 0.25 μm); 280 °C GC injector temperature; GC oven tem-
perature range from 50 °C with the temperature holding of 2 min to
280 °C with temperature holding of 5 min, heating 2 °C/min; helium
3
carrier gas (flow division 50:1) with 1 cm /min flow rate. The mass
The mean size, morphology and elements distribution for supported
nanoparticles were determined by STEM using JEM-2010 microscope
spectrometer used electron ionization with 70 eV ionization energy,
230 °C MS ion source temperature, 150 °C MS quadrupole temperature.
The signals for amines and ketones were integrated as ions with a
maximum contribution in the total ion current (70 ± 0.5 m/z for
amines and 112 ± 0.5 m/z for ketones, respectively). The total ion
current for each signal was calculated as a maximum intensity of the ion
current to maximum intensity ion contribution in the total ion current.
The latter was obtained for all diastereomers by analyzing the men-
thones and methylamines mixtures as a maximum intensity ion current
to the total ion current.
(
JEOL, Japan) with a lattice resolution of 0.14 nm at an accelerating
voltage of 200 kV. Prior to analysis, the samples were ultrasonically
deposited from a suspension in ethanol on a copper grid coated with a
carbon film. The mean diameter was evaluated via measuring more
than 150 particles.
The XPS study of the fresh catalysts was performed on photoelectron
spectrometer (SPECS Surface Nano Analysis GmbH, Germany) equipped
with PHOIBOS-150 hemispherical electron energy analyzer, FOCUS-
5
00 X-ray monochromator, and XR-50 M X-ray source with double Al/
TOF values were calculated in two different ways using either moles
of converted menthone oxime (Eq. 1) or formed menthylamines (Eq. 2)
per mole of exposed catalytic site per unit of time corresponding to the
linear part of the kinetic curves according to the following equation:
Ag anode. The core-level spectra were obtained using monochromatic
Al Kα radiation (hν =1486.74 eV) and energy of a fixed analyzer pass
of 20 eV under ultra-high-vacuum conditions. All measured binding
energies were referred to the C1s line of adventitious carbon at
0
n
n
2
84.8 eV. For detailed analysis, the spectra were fitted into several
TOF =
nMe D t
(1)
(2)
peaks after background subtraction using the Shirley method. The fit-
ting procedure was performed using CasaXPS software. The line shapes
were approximated by the sum of Gaussian and Lorentz functions.
na min e
nMe D t
TOF* =
0
where
n
and nare the initial and after 1 h molar amounts of menthone
2.3. Catalytic experiments
oxime, na min eis molar amounts of menthylamines after 1 h, nMe(mol)
the active metal amount in the catalyst, D is the metal dispersion, t is
the reaction time, ranging from 0 to 1 h. The metal dispersion was es-
timated from TEM images for metal nanoparticles using the following
equation D = 8 rMe/dMe, where rMe is the metal radius (nm) and dMe is
the particle mean diameter (nm). Eq. (1) corresponds to overall trans-
formations of menthone including those involving the acid-base prop-
erties of the metal oxide materials, while eq. (2) reflects exclusively
hydrogenation on the surface of gold.
Methanol (JT Baker) and L-menthone (SAFC, trans-/cis-
isomer = 85/15) for the synthesis of menthone oxime were purchased
from commercial suppliers and used as received. Menthone oxime was
synthesized starting from L-menthone according to the method pre-
sented in [19]. Menthylamine mixture and (-)-menthone (pure trans-
isomer) to study the reaction mechanism were synthesized according to
the method presented below.
The catalyst screening was carried out in a batch reactor at 100 °C
under H atmosphere (7.5 bar). In a typical experiment, a mixture of
2
2.4. Synthesis of menthylamine (mixture of stereoisomers)
menthone oxime (1 mmol), methanol (10 mL) and the catalyst (0.150 g,
the active metal to substrate =1.5 mol %) was intensively stirred. To
explore the reaction kinetics, the temperature and hydrogen pressure
were varied in the range of 90−110 °C and 5.5–7.5 bar, respectively.
The catalytic experiments were performed in the kinetic regime. The
internal diffusion limitations were excluded by using the Weisz-Prater
criterion [40]. The impact of external diffusion was avoided by con-
ducting experiments at an appropriate stirring speed (1100 rpm).
The catalyst recyclability was studied by scaling the substrate, sol-
vent and the catalyst threefold keeping the ratio between all of them the
same. After each reaction run the catalysts was washed with methanol,
dried at 100 °C and reused for the next run.
2
.4.1. Method 1
Synthesis of menthylamine was performed according to the method
described in [41]. Sodium borohydride (2.8 g, 75 mmol) was added to
the solution of (2S,5R)-2-isopropyl-5-methylcyclohexanone oxime
(
2.1 g, 12 mmol) and NiCl
2
·6H O (5.7 g, 24 mmol) in MeOH (40 mL) at
2
−
40 °C during 4 h. The resulting mixture was stirred 2 h at −40 °C and
then overnight at room temperature. The saturated ammonia solution
20 mL) was added followed by filtering the mixture and extracting
with diethyl ether (100 mL). The combined organic layer was washed
(
with brine (20 mL), dried over Na
2
SO and evaporated yielding the
4
mixture of menthylamines (65 %, 1.3 g, 8.1 mmol). This mixture was
analyzed by high resolution gas chromatography. All four diastereoi-
somers were formed, with neomenthylamine being the main product
During the reaction the samples of the volume of ca. 0.1−0.2 ml
were periodically withdrawn and analyzed by gas chromatography:
7
3
820A gas chromatograph (Agilent Tech., USA), HP-5 column (length
0 m, inner diameter 0.25 mm and film thickness 0.25 μm), flame io-
1
according to H-NMR. The spectrum of the pure neomenthylamine is
presented in [42]. Menthylamine and isomenthylamine were assigned
using the amines mixture obtained by the method 2 (see below). After
the signals of neoisomenthylamine were identified by excluding signals
of other isomers, the ratio of amines was calculated as
nization detector operating at 300 °C, helium carrier gas (flow rate
2
mL/min, flow division 5:1), temperature range from 120 °C to 280 °C,
heating 20 °C/min. Additionally the structure of the products was
confirmed by gas chromatography - mass spectrometry (Agilent Tech.
6
0.0:21.0:0.5:18.5 (neomenthylamine
:
menthylamine
:
iso-
7
890 A gas chromatograph with an Agilent 5975C quadrupole mass
menthylamine : neoisomenthylamine).
spectrometer, HP-5 MS column, length 30 m, inner diameter 0.25 mm
and film thickness 0.25 μm, helium carrier gas, flow rate 1 mL/min,
flow division 10:1, temperature range from 50 °C to 280 °C, heating
2.4.2. Method 2
1
13
1
5 °C/min). H- and C-NMR spectra were recorded using a Bruker
Menthylamine was synthesized following [43]. Sodium (1.1 g,
49 mmol) was added to the solution of (2S,5R)-2-isopropyl-5-methyl-
cyclohexanone oxime (0.75 g, 4.4 mmol) in absolute ethanol (5.6 mL)
under reflux. After the reaction was completed, the mixture was diluted
by ethanol (4.7 mL) and treated upon cooling by 2.5 M HCl (20 mL) and
10 % NaOH (20 mL) solutions consequently, followed by extraction of
1
13
DRX-500 spectrometer 500.13 MHz ( H) and 125.76 MHz ( C) in
1
CDCl
3
and Bruker AV-400 spectrometer 400.13 MHz ( H) and
1
3
1
00.61 MHz ( C) in CDCl . A ratio of stereomeric menthylamines and
3
menthones was determined by high resolution gas chromatography on
Agilent 7200 Accurate Mass Q-TOF GC/MS under following conditions:
3

Y.S. Demidova, et al.
Applied Catalysis A, General 605 (2020) 117799
amines by diethyl ether (3 x 30 mL). The organic layer was washed with
catalyst Au4f spectrum was partly overlapping with the Mg2s spectrum.
brine (20 mL), dried over Na
2
SO and evaporated yielding the mixture
4
of menthylamines (82 %, 0.57 g, 3.6 mmol). According to [44] only
menthylamine and isomenthylamine could be formed. We found by
NMR that menthylamine was mainly formed while isomenthylamine
and neomenthylamine were minor products. The spectra of the in-
dividual isomer are presented in [45].
3.2. Catalytic results
3.2.1. Catalytic properties of synthesized Au catalysts. Effect of the support
nature
In the current study Au catalysts were used for menthone oxime
hydrogenation aiming at the development of a catalytic method for
menthylamine synthesis and, in general, finding approaches for stereo-
and chemoselective hydrogenation of oximes to amines. First, gold
nanoparticles supported over different metal oxides such as MgO,
2.5. Synthesis of (-)-menthone
Synthesis of (-)-menthone was performed according to the method
described elsewhere [46]. Commercially available L-menthone re-
presents a mixture of trans- and cis-isomers (85:15). In the current study
the trans-isomer was used to explore the reaction scheme. Pyridinium
chlorochromate (0.64 g, 3.0 mmol) and silica gel 60 (0.64 g) were
ground. The powder was suspended in dichloromethane (6.5 mL) and a
solution of (-)-menthol (Sigma-Aldrich, 0.31 g, 2.0 mmol) in di-
chloromethane (1.5 mL) was added to the resulted mixture. The sus-
pension was stirred at room temperature for 5 h, eluted with diethyl
ether (20 mL), filtered through silica gel end evaporated yielding
Al
2
O
3
, ZrO
2
, TiO were tested in menthone oxime hydrogenation at
2
100 °C and hydrogen pressure of 7.5 bar using methanol as a solvent to
determine an optimal catalyst for a further study of kinetic regularities.
As mentioned above hydrogenation of methone oxime is of interest
to produce valuable menthylamine (Fig. 1). While menthylamine has
three stereocenters, in the current case only two of them were involved
in catalytic processes resulting in four diastereoisomers. The kinetics of
the diastereomers formation is discussed below. The second possible
direction of the reaction is deoximation to menthone. The route is in-
teresting as an approach for selective deoximation, which in some cases
can be of practical interest [20,53]. The reaction scheme was proposed
based on the earlier discussed mechanism of the oximes hydrogenation
in the presence of Pd complexes [54]. Note that the intermediate imine
seems to be not stable and was not detected in the reaction mixture.
It is worth to note that the metal oxides per se were shown to be
active in menthone oxime deoximation producing selectively menthone
(Table 2). No menthylamine was, however, observed in their presence.
Moreover, catalytic activity was noticeably lower compared to the
corresponding Au-containing catalysts.
(
-)-menthone. For removing traces of chromium impurities prior to
catalytic experiments a solution of (-)-menthone in hexane (10 mL) was
washed by 0.05 M EDTA (50 mL), the organic layer was washed with
brine (5 mL) dried over Na
2
SO and solvent was evaporated. The yield
4
1 13
of (-)-menthone was 94 % (0.29 g, 1.9 mmol). NMR H and C are
given in Supplementary Materials.
3
. Results and discussion
3.1. Catalysts characterization
Catalytic behavior was seen to be dependent on the gold nano-
particles size and the support nature (Table 2). Au nanoparticles sup-
ported on titania with an average particle size 4.9 nm promoted men-
thone oxime deoximation giving trans- and cis-menthones. The decrease
in Au nanoparticles size to 3.0 nm resulted in predominant menthyla-
Specific surface area and porosity of oxides used as supports were
determined by nitrogen adsorption. The results are presented in
Table 1. Based on XRF the metal loading in the catalysts was in
agreement with the theoretical one being ca. about 2 wt. Au %.
According to TEM data Au nanoparticles were characterized with an
almost semispherical shape practically without well detectable crys-
tallographic planes. Typically, the catalysts were characterized with a
uniform and narrow distribution of metal particles. Note, in the case of
mine formation. Gold supported on other metal oxides (TiO2, ZrO ,
2
Al
2
O ) with the average Au nanoparticle size ranging from 2.0–3.0 nm
3
showed similar selectivity to the products and catalyzed hydrogenation
of the oxime to the amino group. In the case of gold nanoparticles
supported on MgO with a strong basic character selectivity to men-
thylamine decreased noticeably and deoximation to menthone mainly
occurred with selectivity of 53 %.
Au/TiO catalysts synthesized during 24 h some agglomerates with Au
2
nanoparticles size of ca. 20 nm were detected by TEM. The agglomer-
ates were found only in a negligible fraction not affecting the mono-
modal size distribution of gold nanoparticles as well as the average
particle size. The latter values are summarized in Table 2, while TEM
micrographs are presented in Supplementary Material. In the case of
Turnover frequency (TOF) for a series of gold catalysts over dif-
ferent metal oxides depends strongly on the acid-base properties of
support (Table 2). A similar trend was observed for TOF* values re-
presenting efficiency of the amine formation over Au catalysts (Eq. 2)
(Table 2).
Au/TiO catalysts two type of catalysts were synthesized depending on
2
the preparation technique with average particle sizes of 3.0 and 4.9 nm.
XPS was used to study the chemical state of gold giving the Au4f
core-level spectra shown in Fig. 2. The Au4f spectra were characterized
by the Au 4f7/2-Au 4f5/2 doublet, where the peak integral intensities are
related as 4:3 and the spin-orbit splitting is 3.67 eV. Only metallic Au
species were found for the synthesized catalysts. Depending on the
support a slight shift of the Au4f7/2 peak was observed. Typically, the
binding energy of metallic bulk gold is 84.0 eV. At the same time, Au
nanoparticles show a significant shift of the electron binding energy of
core levels compared with the bulk values [47]. Moreover, the core
level values were demonstrated to depend on the metal oxide support.
Particularly, Claus et al. proposed that the binding energy of an electron
is influenced by the coordination number of the respective atom, being
strongly related to the particle–support interactions [47]. Different
position of Au4f7/2 peak found in the present work may be related to
different character of the particle-support interactions in the tested
catalysts. Au nanoparticles supported on titania was 83.7 eV, while for
gold supported on alumina, magnesia and zirconia the binding energy
values of Au4f7/2 peak were 83.8 eV, respectively, being in a good
agreement with the literature data [38,48–52]. Note that for Au/MgO
Similar to Shimizu et al. [32] analysis of TOF values for gold cata-
lysts along with the electronegativity of the metal ions in metal oxides
supports demonstrated that both acidic and basic sites of the support
played an important role in menthone oxime hydrogenation to men-
thylamine. Electronegativity of the metal or a corresponding ion cal-
culated based on the Pauling approach determines the acid–base
properties of metal oxides in the way that an increase in electro-
negativity increases acidity of the metal oxide surface. For applied in
this work metal oxides electronegativity of the metals or their ions in
support
Al < ZrO
the gold particle size ranging from 2.0–3.0 nm was achieved using Au/
increases
in
the
following
order:
MgO <
2
O
3
2
< TiO
2
. The highest TOF value among the catalysts with
Al
2
O . Gold deposited on the support with a basic character such as
3
MgO and on more acidic metal oxides such as ZrO
almost the same catalytic activity.
2
and TiO showed
2
Thus, small Au nanoparticles (2−3 nm) favored oxime group hy-
drogenation to amine, whereas the influence of the support nature is
also traced. In fact, the former result can be caused by more efficient
hydrogen activation over smaller gold nanoparticles [55,56]. On the
4

Y.S. Demidova, et al.
Applied Catalysis A, General 605 (2020) 117799
Table 2
Average particle sizes according to TEM measurements and catalytic properties of gold catalysts after 7 h. The reaction conditions: T =100 °C, p (H
menthone oxime 1 mmol, solvent 10 mL, catalyst 150 mg (Me/menthone oxime =1.5 mol.%).
2
) =7.5 bar,
d
−1
e
−1
Sample
NPs size, nm
Solvent
TOF , h
TOF* , h
Conversion, %
Selectivity, %
Menthylaminesf
Menthonesf
TiO
ZrO
Al
MgO
Au/TiO
Au/TiO
Au/TiO
Au/TiO
2
2
O
–
–
methanol
methanol
methanol
methanol
methanol
methanol
methanol
toluene
–
–
–
–
–
–
5.6
14.2
14.2
9.2
14
20
38
22
82
73
80
99
0
0
0
0
10
62
61
29
82
100
92
2
3
91
70
13
13
66
a
c
2
4.9
3.0
54
21
21
32
2
2
2
Au/ZrO
2
2
2.1
2.0
methanol
18
12.3
79
67
13
c
Au/ZrO
methanol
18
12.3
85
66
13
Au/Al
Au/Al
Au/Al
Au/Al
2
O
2
O
2
O
2
O
3
3
3
3
methanol
toluene
hexane
THF
30
45
34
19
20.1
19.3
16.5
8.3
99
98
97
65
64
43
48
45
18
41
37
48
Au/MgO
3.0
methanol
20
4.7
63
24
53
Au/MgOc
methanol
20
4.7
76
26
57
b
The reaction was performed using toluene as a solvent;
a
with the concentration of 5 × 10−4 M during 24 h;
Au/TiO
2
catalyst was synthesized using an aqueous solution of HAuCl
4
c
d
e
f
Conversion after 9 h;
Total turnover frequency was calculated after 1 h according to Eq. 1;
Total turnover frequency was calculated after 1 h according to Eq. 2;
Overall selectivity to menthylamine and menthone, respectively.
other hand, the acid–base properties of the support can affect the dis-
sociative adsorption of hydrogen on the surface of gold catalysts and
the substrate adsorption [32]. Detailed discussion on the mechanism
scheme based on the obtained results is presented below. Based on the
quantitatively described based on the transition state theory and the
Kirkwood treatment [22]. The applied theory considered a reaction
between ions and dipolar molecules or between two dipolar molecules
and the influence of the solvent polarity on the reaction kinetics.
In the current work the effect of the solvent nature on the reaction
regularities was explored using apolar and aromatic, polar aprotic and
protic solvents, such as hexane, toluene, tetrahydrofuran (THF), me-
thanol, respectively. Note that the solvent effect was studied using the
gold catalyst. The experiments with the gold catalyst and particularly
with Au nanoparticles supported on titania with an average particle size
catalysts screening, Au/Al
2
O catalyst with the gold nanoparticles size
3
of 2.0 nm as more active and selective in menthone oxime hydrogena-
tion to menthylamine among the tested catalysts was selected for the
kinetic study.
3
.2.2. Solvent effect
4
.9 nm revealed that not only the active sites of the support but also Au
species are involved in menthone oxime deoximation. Indeed Au/TiO
promoted menthone oxime deoximation giving trans- and cis-men-
thones with the total yield of 57 % compared to 11 % over TiO per se
after 7 h (Table 2). Since the influence of Au is more important for
Crucial effect of the solvent nature on the hydrogenation regula-
2
rities is well known [57]. The solvent can affect the active sites of the
catalyst, intermediates/products, reactants etc. Particularly, in our
previous work the effect of solvent on the catalytic activity and ste-
reoselectivity in carvone hydrogenation to dihydrocarvone was
2
Fig. 2. XPS spectra of Au catalysts (symbols – experimental data, curves – fitting).
5

Y.S. Demidova, et al.
Applied Catalysis A, General 605 (2020) 117799
deoximation than of the support, the impact of the side transformations
depending on the solvent was estimated over the gold catalyst, rather
than over the support per se. Catalytic activity and selectivity to men-
thylamine were significantly influenced by the solvent in the presence
of Au/Al
2
3
O catalyst (Table 2). The highest TOF value was obtained
using toluene, with the following reactivity trend toluene <
hexane < methanol < THF. At the same time methanol provided
noticeably higher selectivity to menthylamine, while other solvents
diminished selectivity to the desired amine in a similar manner because
of menthone oxime deoximation to menthone. In the latter cases
menthones were formed with almost the same selectivity as menthy-
lamines (Table 2). Similarly, toluene utilization in the presence of ti-
tania-supported gold catalyst (Au NPs 3 nm) increased the catalytic
activity along with the decrease in the selectivity to the amine because
of predominant deoximation (Table 2).
In fact, there are numerous parameters that can regulate both the
reaction rate and the selectivity to the reaction products. In particular
activity can be related to hydrogen solubility, which decreases in the
following order: hexane > toluene > THF > methanol [58,59].
Thus, hydrogen concentration in the solution seems not to limit the
reaction. Another parameter is related to competitive adsorption of the
substrates and the solvents on the catalysts surface [57]. However, such
influence is crucial when aromatic solvents like toluene, THF are used
because of strong adsorption of the solvent on the catalysts surface
decreasing the reaction rate. Compared to other solvents applied for
menthone oxime hydrogenation methanol has a tendency for dis-
sociative adsorption on the catalysts, forming alkoxides and additional
surface hydrogen [57,60]. Indeed, accumulation of additional hydrogen
on the gold-support interface can increase selectivity to the desired
amine, being thus significantly higher in methanol. Note that during
menthol oxime hydrogenation in methanol traces of the product of the
interactions between the methoxide and amine were detected in the
reaction mixture. At the same time no transformations of menthone
oxime without molecular hydrogen were initiated over the gold catalyst
in methanol.
Fig. 3. Effect of hydrogen pressure on menthone oxime consumption and
menthylamines formation over Au/Al
2
O catalyst. The reaction conditions: T
3
=
100 °C, p (H ) = 5.5-7.5 bar, menthone oxime 1 mmol, methanol 10 mL,
2
catalyst 150 mg (Me/menthone oxime =1.5 mol.%).
Considering stabilization of the reactants and intermediates by the
solvent it was demonstrated that polar solvents provided a lower re-
action rate of polar substrates conversion because of stronger interac-
tions between the substrate and the solvent [57]. Particularly the re-
action rate of acetophenone hydrogenation was higher in apolar
solvents like toluene [61]. In the current study apolar toluene and
hexane led to higher activity compared to methanol and THF. A simple
analysis considering the transition state theory and the Kirkwood
treatment for elementary reactions does not allow correlation of cata-
lytic activity (TOF in Table 2) with the dielectric constant, which in-
creases in the order: hexane < toluene < THF < methanol. Thus, the
solvent effect on activity and selectivity in menthone oxime is more
complex and cannot be interpreted using a concept of the elementary
reactions dependence on solvent polarity. For instance, already a re-
action mechanism comprising two steps [62] is capable of describing
optima (maxima or minima as in the current case) for the reaction rates
vs. dielectric constant. Moreover, as mentioned above, dissociative
adsorption of the solvent can interfere influencing not only activity, but
also selectivity. In particular, a noticeably higher selectivity to men-
thylamine in methanol as a solvent most likely can be attributed to such
type of adsorption.
Fig. 4. Menthone oxime conversion vs. reaction time at different temperature
over Au/Al
2
3
O catalyst (a) and Arrhenius plot of rate constant of menthone
oxime hydeogenation (b). The reaction conditions: T = 90-110 °C, p (H
7.5 bar, menthone oxime 1 mmol, methanol 10 mL, catalyst 150 mg (Me/
menthone oxime =1.5 mol.%).
2
)
=
amounted to Ф = 0.04, which indicates absence of any influence of the
reaction rate by the substrate diffusion inside the catalyst pores. Due to
this criterion no pore limitation occurs, if the Weisz-Prater modulus for
the first order reaction is below unity, while for the second order re-
action it should be below 0.3. The impact of external diffusion limita-
tions was avoided by conducting experiments at an appropriate stirring
speed (1100 rpm).
The hydrogen pressure had no effect on the oxime consumption and
overall selectivity to menthylamines within the studied interval (Fig. 3).
Thus, the reaction has a zero order with respect to hydrogen pressure.
The experimental data for different temperatures were well described
by the equation corresponding to the first order kinetics (Fig. 4a):
3
.2.3. Formal reaction kinetics
To explore the kinetics of menthone oxime hydrogenation the effect
of the reaction temperature and hydrogen pressure on the reaction rate
and the selectivity to the products was studied in the range 90−110 °C
X = 1 – e−k·t,
(2)
and 5.5–7.5 bar in methanol using Au/Al
depicted in Figs. 3 and 4.
2
O catalyst. The results are
3
where X is conversion and k is the rate constant. Plotting ln(k) versus 1/
T results in a straight line, as shown in Fig. 4b, giving the apparent
activation energy calculated from the slope of the Arrhenius plot equal
to 46 kJ/mol (with 98 % confidence limits). The value of apparent
The internal diffusion limitations were excluded by using the Weisz-
Prater criterion [40]. For the maximal initial oxime hydrogenation rate
−4
−1 −1
(
3 ×10
mol l
s
) the estimated Weisz-Prater modulus was
6

Y.S. Demidova, et al.
Applied Catalysis A, General 605 (2020) 117799
activation energy showed a negligible impact of external diffusion,
since otherwise the apparent activation energy is close to 3−10 kJ/mol
significantly improving efficiency and sustainability of the process.
Note that individual diastereomers can be obtained from the resulting
mixtures by silica gel column chromatography purification [45] or by
crystallization with (+)- and (-)-tartaric acids [63].
[
40].
As mentioned above, in the current study menthylamine was formed
as a mixture of four diastereoisomers, namely neomenthylamine,
menthylamine, isomenthylamine, neoisomenthylamine (Fig. 1). To
identify the diastereoisomers the synthesis of menthylamine was ad-
ditionally performed in the current study. Two different approaches
were applied giving a mixture of stereoisomers with different compo-
sition [41,43]. The oxime reduction by sodium borohydride in the
Similar to menthylamines the formation of trans- and cis-menthone
was not affected by the reaction temperature and hydrogen pressure
(Fig. 5 b, d). The ratio between stereoisomers was close to 4 at almost
complete menthone oxime conversion, with thermodynamically more
stable trans-isomer being obtained predominantly [64,65]. Note that
while the trans-isomer of menthone oxime was used as a starting sub-
strate, both trans- and cis-menthone were detected in the reaction
mixture.
presence of NiCl in methanol resulted in the mixture of diastereoi-
2
somers with ratio calculated as 60.0:21.0:0.5:18.5 (neomenthylamine :
menthylamine : isomenthylamine : neoisomenthylamine). The reduc-
tion of menthone oxime by sodium borohydride in absolute ethanol
gave mainly menthylamine while isomenthylamine and neomenthyla-
mine were formed in minor amounts. In the case of menthone oxime
An attempt to explore in more detail catalytic isomerization of
menthone was performed using neat trans-isomer synthesized by
(-)-menthol oxidation. First, no thermal isomerization of trans-men-
thone occurred under hydrogen atmosphere. Trans-menthone was re-
acting very slowly in the presence of the catalyst under the reaction
conditions resulting in only 5 % trans-menthone conversion to cis-
isomer after 7 h. Addition of menthylamine to trans-menthone in a
stoichiometric amount resulted in 18 % of conversion after 7 h.
Utilization of triethylamine instead of menthylamine suppressed iso-
merization completely. Additionally, no trans-menthone isomerization
occurred under nitrogen pressure both without the amine and in the
presence of menthylamine. Therefore, the results demonstrated a cri-
tical feature of menthone isomerization that the primary amine and
molecular hydrogen are involved in the transformation.
hydrogenation over Au/Al
2
O predominant formation of neomenthy-
3
lamine and neoisomenthylamine was detected in the reaction mixture,
whereas isomenthylamine was observed in trace amounts. The se-
lectivity to the diastereomers on menthone oxime conversion was in-
dependent on both the reaction temperature and the hydrogen pressure
(
Fig. 5 a, c). During the reaction the stereoselectivity slightly changed
being most likely thermodynamically controlled. Indeed the ratio be-
tween diastereoisomers of menthylamine obtained using Au/Al as a
O
2 3
catalyst was close to the value for the synthetic method 1 applied in the
current study (neomenthylamine (60.0 %), menthylamine (21.0 %),
isomenthylamine (0.5 %) and neoisomenthylamine (18.5 %)). Hydro-
genation of menthone oxime to the intermediate imine seems to be the
rate determining step and further hydrogen addition is controlled by
thermodynamics. Based on the literature data in the presence of pla-
tinum black in glacial acetic acid the main product was neomenthyla-
mine, while hydrogenation over Raney nickel in methanol led to pre-
dominant neoisomenthylamine formation [44]. Thus, utilization of
catalysts did not affect the diastereoisomers composition, however,
Thus, a scheme of trans- to cis-menthone isomerization can tenta-
tively be proposed based on the obtained reaction regularities and a
general mechanism of similar transformations. The proposed reaction
intermediate formed during isomerization as a result of the initial
protonation followed by hydrogen subtraction from the α-carbon via
interaction with the amine is presented in Fig. 6. Molecular hydrogen,
as discussed in details below, underwent heterolytic dissociation on the
gold catalyst surface giving hydride ions on gold and protons stabilized
Fig. 5. Selectivity to menthylamines (a, c) and menthones (b, d) vs. reaction time at different reaction temperature and hydrogen pressure. The reaction conditions:
T = 90-110 °C, p (H
2
) = 5.5-7.5 bar, menthone oxime 1 mmol, methanol 10 mL, Au/Al
2
O catalyst 150 mg (Me/menthone oxime =1.5 mol.%).
3
7

Y.S. Demidova, et al.
Applied Catalysis A, General 605 (2020) 117799
Fig. 6. The intermediate of catalytic trans- to cis-menthone isomerization in the presence of menthylamine.
on the support, with the latter being initiated menthone isomerization.
Such heterolytic dissociation of hydrogen over gold catalysts has been
recently discussed in the literature in connection of several hetero-
geneous catalytic reactions [66,67].
previous work a drastic reduction of the catalytic activity was observed
during one-pot myrtenol amination with aniline over Au/ZrO catalyst
2
because of the intermediate imine oligomerization or polymerization
and subsequent blocking of the active sites [72]. At the same time, in
the case of menthone oxime hydrogenation, its conversion was not in-
fluenced giving just a gradual decrease in selectivity to menthylamine.
Thus, deactivation mainly affected the active sites required for hydro-
genation to the amine. An attempt to restore selectivity to menthyla-
Menthone isomerization was earlier studied using both homo-
geneous acidic and basic catalysts including a detailed kinetic study
[
64,68,69]. Bergman observed a larger rate constant for the enolate ion
formation from trans-menthone compared to the corresponding rate
constant for cis-menthone, being considered as a rate-limiting step.
Generally similar reaction mechanisms were proposed in these studies
with some specificities depending on the catalyst nature. In fact, pre-
viously hydrogen was considered as an astoichiometric reactant in cis-
trans isomerization of substituted cyclohexanols, such as for example 4-
tertbutylcyclohexanols [70] or in menthols [71].
mine by Au/Al
2
O catalyst regeneration was performed. The catalyst
3
after the third reaction run was subjected to the treatment in an air flow
up to 450 °C with the heating rate 10°/min. According to TEM data the
gold particle size in Au/Al
2
O did not change after the treatment
3
(Fig. 8b). At the same time catalyst regeneration did not completely
restore the catalytic activity and almost the same catalytic activity and
selectivity to desired menthylamine were achieved as for the third re-
action run (Fig. 7).
Ultimately, to study Au/Al
2
O
3
catalyst recyclability, menthone
oxime hydrogenation was performed in three consecutive experiments.
After each experiment the catalyst was filtered, washed with methanol,
dried at 100 °C and reused, keeping the same ratio between substrates,
the solvent and the catalyst. The catalytic activity increased in each
subsequent experiment, whereas selectivity to menthylamine at the
same value of menthone oxime conversion (95 %) decreased (Fig. 7).
Selectivity to menthones and the side products including the product of
the interactions between the solvent and amine increased in each
subsequent experiment.
3
.2.4. Discussion on the reaction mechanism
In our recent study on monoterpenoid oximes hydrogenation over
platinum catalysts possible reaction scheme was discussed [19]. It was
proposed that the oxime hydrogenation proceeds via imine formation
followed by its further hydrogenation or hydrolysis depending on the
nature of the catalyst [19,54]. Similar to Pt catalysts, no transforma-
tions of menthone oxime to both menthones and menthylamines were
observed without molecular hydrogen over the gold nanoparticles on
metal oxides. At the same time menthylamine was obtained over the
gold nanoparticles with a proper particle size close to 2−3 nm.
Earlier Corma et al. observed oxime formation during hydrogena-
tion of α,β-unsaturated nitrocompounds by molecular hydrogen using a
gold catalyst that tentatively showed some common features in the
substrate activation on the catalyst surface for the reduction of ni-
trocompounds and oximes [31]. Based on DFT calculations, it was
proposed that chemoselective hydrogenation of a nitro group in ni-
The reasons of the catalyst deactivation are most likely related to
strong adsorption of the intermediates or the reaction products, which
can form oligomeric or polymeric structures. Au/Al
2
O catalyst after
3
the third reaction run was characterized by TEM (Fig. 8a). Compared to
the fresh sample the gold particles size increased just slightly while the
carbon deposits, which may block the active sites, were clearly detected
on the surface. Leaching of the active phase, as another reason for
catalyst deactivation, was excluded based on the XRF analysis. In our
trostyrene over Au/TiO
2
proceeded via H
2
dissociation, while en-
ergetically and geometrically favored adsorption through the nitro
group occurred on titania and in the interface between the low co-
ordinated gold nanoparticle and the support [33]. In addition, Shimizu
et al. demonstrated for a highly active Au/Al
2
3
O catalyst using FTIR in-
situ that nitrostyrene interacts with alumina through the nitro group.
Molecular hydrogen underwent heterolytic dissociation on the surface
of Au/Al
2
O giving hydride ions on low coordinated Au atoms and
3
protons stabilized at the oxygen atoms of the support [32,73].
Based on the data obtained in the current study and the literature
data the reaction scheme can be proposed for gold catalysts (Fig. 9). In
the case of menthone oxime hydrogenation independent on the reaction
route the substrate is adsorbed on the metal oxide (MeO, Fig. 9) surface
interacting with it through the oxime group. Subsequently for both
routes activation most likely proceeds via a proton transfer from the
support surface. The presence of gold nanoparticles increased the initial
reaction rate because of heterolytic hydrogen dissociation generating
available hydrogen species [73]. Such dissociation leads to formation of
δ−
δ+
Fig. 7. Menthone oxime conversion after 4 h and selectivity to the main pro-
Au
experimentally and theoretically demonstrated that low coordinated
gold atoms were required for dissociative adsorption of H and the
average number of dissociatively adsorbed hydrogen atoms increased
-H
and MeOH
(Fig. 9). It is worth to emphasize that it was
n
ducts at the same menthone oxime conversion (95 %) at 100 °C and hydrogen
pressure of 7.5 bar for Au/Al
2
O recycling and regeneration in air flow up to
3
2
4
50 °C (10°/min).
8

Y.S. Demidova, et al.
Applied Catalysis A, General 605 (2020) 117799
Fig. 8. TEM micrographs and histograms of Au/Al
2
O
3
catalyst: (a) after third reaction run and (b) the catalyst regeneration in air flow up to 450 °C (10°/min). The
reaction conditions: T =100 °C, p (H ) =7.5 bar, menthone oxime 1 mmol, methanol 10 mL, catalyst 150 mg (Me/menthone oxime =1.5 mol.%).
2
with decreasing the particle size being limited to the gold atoms on
corner and edge positions [55,56]. Thus, smaller gold nanoparticles
provided more efficient hydrogen activation favoring oxime hydro-
menthylamine. Gold nanoparticles and metal oxides used as a support
seem to act in tandem. The initial adsorption of menthone oxime was
proposed to proceed on the support surface, while molecular hydrogen
is dissociated giving a hydride ion on the low coordinated Au atom and
proton stabilized at the oxygen atom of the support. An increase of gold
nanoparticles size and utilization of metal oxides with a strong basic
character such as magnesia favored deoximation to menthone. A higher
catalytic activity and selectivity to menthylamine was achieved in the
+
genation to the amino group via a transfer of H /H- species from the
metal-support interface to the polar bond (Fig. 9). Alternatively, a lack
of active hydrogen species on the catalyst surface as well as metal
oxides with a basic character resulted in a transfer of hydroxyl species
from the support giving menthone (Fig. 9). Note that the presence of
hydroxyl species on the support surface can be related also to dis-
sociative methanol adsorption [74]. In fact, an increase in selectivity to
menthone over gold supported on basic magnesia is in line with this
hypothesis.
presence of Au/Al
oxides such as ZrO
2
O
3
catalyst. Gold supported on more acidic metal
2
and TiO showed a lower catalytic activity com-
2
pared to alumina displaying similar selectivity to menthylamine.
Kinetics of menthone oxime hydrogenation was studied over Au/Al
2 3
O
Therefore, gold nanoparticles seem to act in tandem with the metal
oxide during menthone oxime transformation. Both menthone oxime
and molecular hydrogen activation proceeded by involving active sites
of the support, with the acid-base properties of the support being im-
portant. Gold nanoparticles with a proper size (2−3 nm) provided more
efficient hydrogen activation.
catalyst. The catalytic activity and the selectivity to menthylamine were
noticeably influenced by the solvent nature, with higher selectivity to
the amine achieved using methanol. The reaction has zero and first
orders with respect to hydrogen pressure and menthone oxime con-
centration, respectively. Stereoselectivity to menthylamines and men-
thones was independent on the reaction temperature and the hydrogen
pressure, being more affected by thermodynamics. Au/Al
2
3
O catalyst
recyclability was studied in three consecutive experiments. A gradual
decrease of selectivity to menthylamine was observed, whereas the
catalytic activity did not suffer. The deactivation mainly affected the
active sites required for hydrogenation to the amine most likely related
to strong adsorption of the intermediates or reaction products, which
can form oligomeric or polymeric structures.
4
. Conclusions
In the current study gold nanoparticles supported over different
metal oxides such as magnesia, titania, zirconia and alumina were
utilized for menthone oxime hydrogenation. For the first time gold
catalysts were shown to be efficient for the synthesis of valuable
Fig. 9. A mechanistic scheme of gold-catalyzed menthone oxime hydrogenation (MeO – metal oxide support).
9

Y.S. Demidova, et al.
Applied Catalysis A, General 605 (2020) 117799
CRediT authorship contribution statement
D.V. Korchagina, K.P. Volcho, N.F. Salakhutdinov, A.V. Simakov, D. Yu, Murzin,
Appl. Catal.A: Gen. 464–465 (2013) 348–356.
[
25] Yu.S. Solkina, S. Reshetnikov, M. Estrada, A.V. Simakov, D.Yu. Murzin,
I.L. Simakova, Chem. Eng. J. 176–177 (2011) 42–48.
Yu.S. Demidova: Data curation, Investigation, Writing - original
draft. E.S. Mozhaitsev: Data curation. E.V. Suslov: Methodology,
Conceptualization, Writing - review & editing. A.A. Nefedov: Data
curation. A.A. Saraev: Data curation. K.P. Volcho: Methodology,
Conceptualization, Writing - review & editing. N.F. Salakhutdinov:
Methodology, Conceptualization. A. Simakov: Conceptualization,
[26] C. Milone, R. Ingoglia, A. Pistone, G. Neri, F. Frusteri, S. Galvano, J. Catal. 222
(
2004) 348–356.
[
27] C. Milone, R. Ingoglia, L. Schipilliti, C. Crisafulli, G. Neri, S. Galvano, J. Catal. 236
(
2005) 80–90.
[28] C. Milone, C. Crisafulli, R. Ingoglia, L. Schipilliti, S. Galvano, Catal. Today 122
(2007) 341–351.
[
[
[
29] A.S.K. Hashmi, G.J. Hutchings, Angew. Chem. 45 (2006) 7896–7936.
30] A. Corma, P. Serna, Science 313 (2006) 332–334.
Writing
-
review
&
editing. I.L. Simakova: Methodology,
Conceptualization, Writing
- review & editing. D.Yu. Murzin:
31] A. Corma, P. Serna, H. Garcia, J. Am. Chem. Soc. 129 (2007) 6358–6359.
Conceptualization, Writing - review & editing.
[32] K. Shimizu, Y. Miyamoto, T. Kawasaki, T. Tanji, Y. Tai, A. Satsuma, J. Phys. Chem.
1
13 (2009) 17803–17810.
[
33] M. Boronat, P. Concepciòn, A. Corma, S. Gonzàlez, F. Illas, P. Serna, J. Am. Chem.
Soc. 129 (2007) 16230–16237.
Declaration of Competing Interest
[
[
[
[
34] P. Serna, M. Boronat, A. Corma, Top. Catal. 54 (2011) 439–446.
35] X. Wang, N. Perret, M.A. Keane, Appl. Catal. A Gen. 467 (2013) 575–584.
36] J.A. Becerra, Ó.F. Arbeláez, A.L. Villa, Brazilian J. Chem. Eng. 37 (2020) 1–27.
37] M. Sankar, Q. He, R.V. Engel, M.A. Sainna, A.J. Logsdail, A. Roldan, D.J. Willock,
N. Agarwal, C.J. Kiely, G.J. Hutchings, Chem. Rev. 120 (8) (2020) 3890–3938.
38] E. Smolentseva, B.T. Kusema, S. Beloshapkin, M. Estrada, E. Vargas, D.Y. Murzin,
F. Castillon, S. Fuentes, A. Simakov, Appl. Catal. A Gen. 392 (2011) 69–79.
The authors report no declarations of interest.
Acknowledgements
[
The authors acknowledge the Multi-Access Chemical Research
Center SB RAS and the Center of Collective Use «National Center of
Catalyst Research» of Boreskov Institute of Catalysis for spectral and
analytical measurements. This work was supported by the Russian
Foundation for Basic Research grant № 18-33-20175 and by Ministry of
Science and Higher Education of the Russian Federation project no.
АААА-А17-117041710075-0.
[39] S. Ivanova, V. Pitchon, Y. Zimmermann, C. Petit, Appl. Catal. A 298 (2006) 57–64.
[
[
[
40] D. Murzin, T. Salmi, Catalytic Kinetics, Elsevier, Amsterdam, 2005, pp. 341–418.
41] Y. Zhou, J. Dong, F. Zhang, Y. Gong, J. Org. Chem. 76 (2) (2011) 588–600.
42] T.C. Pickel, G.J. Karahalis, C.T. Buru, J. Bacsa, C.C. Scarborough, Eur. J. Org. Chem
2018 (48) (2018) 6876–6889.
[
[
[
43] H. Feltkamp, F. Koch, T.N. Thanh, Justus Liebigs Ann. Chem. 707 (1967) 78–86.
44] N.G. Kozlov, Chem. Nat. Compd. 18 (2) (1983) 131–143.
45] J. Kulisch, M. Nieger, F. Stecker, A. Fischer, S.R. Waldvogel, Angew. Chem. 50 (24)
(2011) 5564–5567.
[
[
[
46] Y. Murakami, Y. Takeda, S. Minakata, J. Org. Chem. 76 (15) (2011) 6277–6285.
47] J. Radnik, C. Mohr, P. Claus, Phys. Chem. Chem. Phys. 5 (2003) 172–177.
48] F.-W. Chang, H.-Y. Yu, L.S. Roselin, H.-C. Yang, T.-C. Ou, Appl. Catal. A Gen. 302
References
(
2006) 157–167.
[
[
[
1] N.F. Salakhutdinov, K.P. Volcho, O.I. Yarovaya, Pure Appl. Chem. 89 (8) (2017)
[49] P. Konova, A. Naydenov, C. Venkov, D. Mehandjiev, D. Andreeva, T. Tabakova, J.
Mol. Catal. 213 (2004) 235–240.
1
105–1118.
2] E. Lück, Gvon R. Lipinski, Foods, 3. Food Additives, Ulmann’s Encycl. Ind.
Chemostry, (2012), pp. 671–692.
[50] I.L. Simakova, Yu.S. Demidova, M. Estrada, S. Beloshapkin, E.V. Suslov,
K.P. Volcho, N.F. Salakhutdinov, D.Yu. Murzin, A. Simakov, Catal. Tod. 279 (2017)
63–70.
3] Z. Rappoport, J.F. Liebman, The Chemistry of Hydroxylamines, Oximes and
Hydroxamic Acids, John Wiley & Sons, Ltd, 2009.
[51] Yu.S. Demidova, I.L. Simakova, M. Estrada, S. Beloshapkin, E.V. Suslov,
D.V. Korchagina, K.P. Volcho, N.F. Salakhutdinov, A.V. Simakov, D.Yu. Murzin,
Appl. Catal. A Gen. 464–465 (2013) 348–356.
[
[
4] N.G. Kozlov, Chem. Nat. Compd. 18 (1982) 131–143.
5] S. Kumar, M.E. Sobhia, U. Ramachandran, Tetrahedron Asymmetry 16 (2005), pp.
2
599–2605.
[52] X. Cao, J. Zhou, H. Wang, S. Li, W. Wang, G. Qin, J. Mater. Chem. A 7 (2019)
10980–10987.
[
[
[
[
6] M. Steinbeck, G.D. Frey, W.W. Schoeller, W.A. Herrmann, J. Organomet. Chem. 696
(
2011) 3945–3954.
[53] K.-G. Fahlbusch, F.-J. Hammerschmidt, J. Panten, W. Pickenhagen, D. Schatkowski,
K. Bauer, H. Surburg, Flavors and fragrances, Ullmann’S Encyclopedia of Industrial
Chemistry 15 Wiley-VCH Verlag GmbH & Co. KGaA, 2003, pp. 73–198.
[54] Y. Liu, Z. Quan, S. He, Z. Zhao, J. Wang, B. Wang, React. Chem. Eng. 4 (2019)
1145–1152.
7] V.M. Uvarov, D.A. de Vekki, V.P. Reshetilovskii, N.K. Skvortsov, Russ. J. Gen.
Chem. 80 (2010) 35–46.
8] D.A. de Vekki, V.M. Uvarov, A.N. Reznikov, N.K. Skvortsov, Russ. Chem. Bull. 57
(
2008) 349–357.
9] D. Ma, K. Cheng, Tetrahedron Asymmetry 10 (1999) 713–719.
[55] A. Corma, M. Boronat, S. Gonzàlez, F. Illas, Chem. Commun 32 (2007) 3371–3373
2007.
[
[
10] Y. Zhou, Q. Liu, Y. Gong, Org. Biomol. Chem. 10 (2012) 7618–7627.
11] P.C. Bulman Page, G.A. Rassias, D. Barros, D. Bethell, M.B. Schilling, J. Chem. Soc.
Perkin Trans. I 1 (2) (2000) 3325–3334.
[56] E. Bus, J.T. Miller, J.A. van Bokhoven, J. Phys. Chem. B 109 (2005) 14581–14587.
[57] J.J. Varghese, S.H. Mushrif, React. Chem. Eng. 4 (2019) 165–206.
[58] E. Brunner, J. Chem. Eng. Data 30 (3) (1985) 269–273.
[59] Hydrogen and deuterium, Solubility Data Series 5/6 Pergamon Press, Oxford, 1981
646.
[
12] P.C.B. Page, G.A. Rassias, D. Bethell, M.B. Schilling, A J. Org. Chem. 63 (1998)
2
774–2777.
[
[
13] Y. Zhou, Y. Gong, Asymmetric Eur. J. Org. Chem. (2011) 6092–6099.
14] B. Bömer, R. Großer, W. Lange, U. Zweering, B. Köhler, W. Sirges, M. Grose-Bley,
DE19546136A1, Chem. Abstr. 1997 (127) (1997) 96037.
[60] Yu.S. Demidova, E.V. Suslov, I.L. Simakova, K.P. Volcho, E. Smolentseva,
N.F. Salakhutdinov, A.V. Simakov, D.Yu. Murzin, Mol. Catal. 433 (2017) 414–419.
[61] N.M. Bertero, A.F. Trasarti, C.R. Apesteguía, A.J. Marchi, Appl. Catal. A Gen. 394
(2011) 228–238.
[
[
15] G. Ortar, L. De Petrocellis, L. Morera, A.S. Moriello, P. Orlando, E. Morera, M. Nalli,
V. Di Marzo, Bioorganic Med. Chem. Lett. 20 (2010) 2729–2732.
16] A. Dore, B. Asproni, A. Scampuddu, S. Gessi, G. Murineddu, E. Cichero, P. Fossa,
S. Merighi, S. Bencivenni, G.A. Pinna, Bioorg. Med. Chem. Lett. 24 (2016)
[62] D.Yu. Murzin, Catal. Sci. Technol. 6 (2016) 5700–5713.
[63] N. Welschoffa, S.R. Waldvogel, Synthesis 21 (2010) 3596–3601.
[64] N. Bergman, Acta Chem. Scand. A 33 (1979) 577–582.
[65] B. Rickborn, J. Am. Chem. Soc. 84 (1962) 2414–2417.
[66] T. Whittaker, K.B. Sravan Kumar, C. Peterson, M.N. Pollock, L.C. Grabow,
B.D. Chandler, J. Am. Chem. Soc. 140 (48) (2018) 16469–16487.
[67] R. Juárez, S.F. Parker, P. Concepción, A. Corma, H. García, Chem. Sci. 1 (2010)
731–738.
5
291–5301.
[
[
[
17] C. Edinger, J. Kulisch, S.R. Waldvogel, Beilstein J. Org. Chem. 11 (2015) 294–301.
18] H. Feltkamp, F. Koch, T.N. Thanh, Justus Liebigs Ann. Chem. 707 (1967) 78–86.
19] Yu.S. Demidova, E.S. Mozhaitsev, A.A. Munkuev, E.V. Suslov, A.A. Saraev,
K.P. Volcho, N.F. Salakhutdinov, I.L. Simakova, D. Yu, Murzin, Top. Catal. 63
(
2020) 187–195.
[
[
20] Yu.S. Demidova, E.V. Suslov, O.A. Simakova, I.L. Simakova, K.P. Volcho,
N.F. Salakhutdinov, D. Yu, Murzin, J. Mol. Catal. 420 (2016) 142–148.
21] K.-G. Fahlbusch, F.-J. Hammerschmidt, J. Panten, W. Pickenhagen, D. Schatkowski,
K. Bauer, H. Surburg, Flavors and Fragrances. In Ullmann’s Encyclopedia of
Industrial Chemistry 15 Wiley-VCH Verlag GmbH & Co. KGaA, 2003, pp. 73–198.
22] Yu.S. Demidova, E.V. Suslov, O.A. Simakova, I.L. Simakova, K.P. Volcho,
N.F. Salakhutdinov, D. Yu, Murzin, Catal. Today 241 (2015) 189–194.
23] P. Claus, Appl. Catal. A Gen. 291 (2005) 222–229.
[68] J.F. Bunnett, L.A. Retallick, J. Am. Chem. Soc. 89 (1967) 423–428.
[69] Y. Pocker, R.F. Buchholz, J. Am. Chem. Soc. 93 (1971) 2905–2909.
[70] D.Yu. Murzin, React. Kinet. Catal. Lett. 34 (1993) 495–499.
[71] B. Etzold, A. Jess, M. Nobis, Catal. Today 140 (1-2) (2009) 30–36.
[72] Yu.S. Demidova, I.L. Simakova, J. Wärnå, A.V. Simakov, D.Yu. Murzin, Chem. Eng.
J. 238 (2014) 164–171.
[
[73] E. Bus, J.T. Miller, J.A. van Bokhoven, Phys. Chem. B 109 (30) (2005)
14581–14587.
[
[
24] Yu.S. Demidova, I.L. Simakova, M. Estrada, S. Beloshapkin, E.V. Suslov,
[74] M.M. Branda, R.M. Ferullo, P.G. Belelli, N.J. Castellani, Surf. Sci. 527 (2003) 89–99.
10