Preparation of Betulone Via Betulin Oxidation Over Ru Nanoparticles Deposited on Graphitic Carbon Nitride

Article abstract of DOI:10.1007/s10562-018-02649-8

Derivatives of betulin obtained by oxidation have broad pharmacological applications, demonstrating anti-inflammatory, antioxidant, hepatoprotective, and anticancer activity. Ru supported catalysts based on graphitic carbon nitride or N-doped carbon were prepared via a mild reduction of the initial Ru precursor with hydrazine. These catalysts along with Ru supported on carbon nanofibers and a mesoporous carbon support Sibunit were studied in catalytic oxidation of betulin. Ru/carbon nitride demonstrated catalytic activity in betulin oxidation higher than Ru/N-doped carbon (conversion of betulin up to ca. 70% and 30%, respectively). Selectivity to different oxidation products was dependent on the properties of the carbon supports.

Full text of DOI:10.1007/s10562-018-02649-8

Catalysis Letters
https://doi.org/10.1007/s10562-018-02649-8
Preparation of Betulone Via Betulin Oxidation Over Ru Nanoparticles
Deposited on Graphitic Carbon Nitride
1
,2
2
2
3
4,5
6
7
N. D. Shcherban · P. Mäki‑Arvela · A. Aho · S. А. Sergiienko · M. A. Skoryk · E. Kolobova · I. L. Simakova ·
2
2
2
2
K. Eränen · A. Smeds · J. Hemming · D. Yu. Murzin
Received: 5 July 2018 / Accepted: 9 December 2018
©
The Author(s) 2019
Abstract
Derivatives of betulin obtained by oxidation have broad pharmacological applications, demonstrating anti-inflammatory, anti-
oxidant, hepatoprotective, and anticancer activity. Ru supported catalysts based on graphitic carbon nitride or N-doped carbon
were prepared via a mild reduction of the initial Ru precursor with hydrazine. These catalysts along with Ru supported on
carbon nanofibers and a mesoporous carbon support Sibunit were studied in catalytic oxidation of betulin. Ru/carbon nitride
demonstrated catalytic activity in betulin oxidation higher than Ru/N-doped carbon (conversion of betulin up to ca. 70%
and 30%, respectively). Selectivity to different oxidation products was dependent on the properties of the carbon supports.
Graphical Abstract
Keywords Betulin oxidation · Carbon nitride · Ruthenium · Betulone
Electronic supplementary material The online version of this
article (https://doi.org/10.1007/s10562-018-02649-8) contains
supplementary material, which is available to authorized users.
4
*
D. Yu. Murzin
NanoMedTeсh LLC, 68 Gorkogo str., Kiev, Ukraine
dmurzin@abo.fi
5
6
7
G.V. Kurdyumov Institute for Metal Physics,
N.A.S. of Ukraine, 36 Academician Vernadskiy av.,
Kiev 03680, Ukraine
1
L.V. Pisarzhevsky Institute of Physical Chemistry, National
Academy of Sciences of Ukraine, 31 pr. Nauky, Kiev 03028,
Ukraine
Research School of Chemistry & Applied Biomedical
Sciences, Tomsk Polytechnic University, Lenin Avenue 30,
Tomsk 634050, Russia
2
3
Johan Gadolin Process Chemistry Centre, Åbo Akademi
University, Biskopsgatan 8, 20500 Åbo/Turku, Finland
Boreskov Institute of Catalysis, Lavrentieva ave. 5,
Novosibirsk, Russia
National University of Science and Technology MISiS,
Leninskii pr. 4, 119049 Moscow, Russia
Vol.:(0
1
123456789)
3

N. D. Shcherban et al.
1
Introduction
synthetic air at 108 °C in toluene to betulinic aldehyde
[
5]. The presence of silica in the reaction mixture leads to
Betulin is a natural compound from a class of lupane-type
pentacyclic triterpenes possessing interesting biological
properties [1–3]. Betulin derivatives obtained by oxidation
a significant increase in the betulin conversion (41% and
20%, respectively, after 24 h) with similar selectivity (67%
and 66%, respectively). The use of ruthenium nanoparti-
cles deposited on an acidic carbon support results in the
formation of allobetulin as the main reaction product [5].
Another betulin derivative, betulone, is present in
quite low quantities in many plants [22, 23]. Regarding
its biological activity it was noted that selective oxidation
of 3-hydroxyl group in the initial compound results in a
significant increase in biological activity compared with
betulin (regulation of melanin biosynthesis, anticancer
activity etc.) [24, 25]. Moreover, betulone can be used
as the main building block for the synthesis of another
valuable product allobetulone [26]. Betulone was prepared
from betulin through regioselective oxidation using grow-
ing microorganism cells as catalyst [1].
(
Fig. 1) have a wide spectrum of pharmacological action,
which include anti-inflammatory, antioxidant, hepatoprotec-
tive, anticancer and other ones [4–10]. Lupane-type com-
pounds have antitumor activity, among them the strongest
effect is belonging to betulinic acid, which is recognized
as an effective inhibitor of the growth of cancer cells [11].
Betulin, betulinic acid and betulonic acid are also interesting
from the medical point of view as a basis for creation of new
antiviral medicines showing inhibitory effect. Allobetulin
has a moderately expressed effect on the influenza virus type
B [12].
Betulonic acid is prepared via betulin oxidation in acetone
with the Jones reagent [13–15]. This compound can also be
obtained as a result of betulin oxidation with a pyridine-
dichromate complex with acetic anhydride in dimethylfor-
mamide [16] and chromium (VI) oxide in acetic acid [17].
Betulinic aldehyde is formed as a result of betulin oxi-
dation with potassium dichromate on silica gel in dichlo-
romethane [18]. Reaction between betulin and chlorochro-
mate or pyridinium dichromate in dichloromethane leads to
formation of betulonic aldehyde [19]. Synthesis of betulinic
acid consists of reduction of betulonic acid with sodium
borohydride [15] (Fig. 1). For oxidation of betulin to betu-
linic acid with iodine or (diacetoxyodo)benzene as oxidants,
TEMPO (2,2,6,6-tetramethylpiperidine oxyl) as a catalyst
was also used [20]. When RuCl (PPh ) as a homogene-
Graphitic carbon nitride possessing besides interest-
ing electronic properties also catalytic activity due to the
presence of Lewis basic sites [27] seems to be a suitable
support for preparation of catalysts active in betulin oxida-
tion. The number of publications devoted to investigations
of catalytic performance of Ru nanoparticles supported
on graphitic C3N4 is rather limited. For instance, Ru/g-
C3N4 demonstrated promising catalytic activity and a high
turnover frequency number in the hydrolysis of ammonia
borane which provides an eco-friendly and sustainable
way to hydrogen production [28]. Deposition of Pt50–Ru50
alloy catalyst on nanoporous graphitic C3N4 as a support
allowed to increase the anodic performance in direct meth-
anol fuel cells due to well-developed three-dimensionally
interconnected porosity of the support [29].
2
3 3
ous catalyst and TEMPO as a co-catalyst were also used for
betulin oxidation in oxygen, the yields of betulinic aldehyde
at 1 bar and 105 °C and 8 bar and 100 °C were 15% (27 h)
and 69% (8 h), respectively [21].
The aim of the current study was to investigate betulin
oxidation over ruthenium nanoparticles supported on gra-
phitic carbon nitride. For comparison, nitrogen-containing
carbon and several undoped carbons were also used as
supports.
Use of Ru/C as a catalyst in a mixture with the basic
hydrotalcite and silicon dioxide as a dehydrating agent
allowed to perform selective oxidation of betulin with
Fig. 1 Scheme of betulin oxida-
tion
1
3

Preparation of Betulone Via Betulin Oxidation Over Ru Nanoparticles Deposited on Graphitic…
2
Experimental
in 250 ml of deionized water. The support sample (0.3 g)
was added to the resulting solution and stirred at a room
temperature for ca. 16 h. After water evaporation the resi-
due was dried at 120 °C for 3 h. The resulting sample was
stirred in 100 ml of 0.1 M KOH (Merck, 85%) solution at a
room temperature for 10 min, thereafter hydrazine (Merck,
80%) was added (molar ratio of hydrazine:ruthenium was
2), slowly heated up to 80 °C, and maintained at this tem-
perature for 1 h. The sample was filtered, washed with
distilled water to a neutral pH of wash water and dried at
100 °C.
2.1 Sample Preparation
Initial samples of nanostructured graphitic carbon nitride
and N-doped carbon were obtained by bulk and hard tem-
plate method using melamine, as well as sucrose and mela-
mine as precursors, respectively.
The material denoted as C N –1 was prepared via bulk
3
4
pyrolysis of melamine (Chimlaborreactiv, 99%). For this
purpose melamine was placed in the middle of the quartz
tube, followed by heating in an inert atmosphere (argon)
at 500 °C for 2 h. As a result yellow carbon nitride pow-
der was obtained. C N –2 was synthesized using a similar
Two Ru catalysts were synthesized using different
undoped carbons: carbon nanofibers of the platelet struc-
ture (CNF-Pl) (fraction 50-120m, FutureCarbon GmbH,
R141402333-01) and a mesoporous carbon material Sibunit
(fraction 50-120m). The catalyst denoted as Ru-CNF (2 wt%
Ru) was prepared by immobilization on CNF-Pl colloidal
Ru nanoparticles (0.1 M) synthesized by the polyol method
using RuCl3·nH2O and ethylene glycol (EG) as a metal
precursor and a reducing agent, respectively, and polyvi-
nylpyrrolidone (PVP) as a stabilizing agent. As a general
procedure, RuCl3·nH2O and PVP (mol Ru/mol monomers
PVP=1/5) were dissolved in EG under stirring followed by
heating up to 198 °C for 1 h. Ru nanoparticles supported on
CNF-Pl were subjected to thermal treatment in air at 180 °C
with a temperature ramp 10 K/min during 0.5 h followed
by reduction in hydrogen at 250 °C with temperature ramp
1.5 K/min during 1 h to remove excess of PVP [31]. The
catalyst denoted as Ru-Sib-Imp (3 wt%) was prepared by
impregnation of Sibunit with RuCl3 ×nH2O aqueous solu-
tion (0.1 M) [32] followed by oxidation in air at 150 °C dur-
ing 1.5 h and reduction in hydrogen until 440 °C during 6 h
with temperature ramp 10 K/min. The metal loading in those
catalysts was measured by XRF.
3
4
technique, except that the heat treatment was carried out
in air. For synthesis of C N –MCF a weighed amount of
3
4
MCF mesoporous silica was mixed with an aqueous solu-
tion containing a certain amount of melamine and hydro-
chloric acid (Lachema, 35%) used for melamine binding
into the salt in order to reduce its sublimation (ca. 2.356 g
of melamine and 1.8 ml of concentrated hydrochloric acid
for 0.5 g of MCF). The resulting suspension was stirred
on a magnetic stirrer at a room temperature for 3 h and
dried at 40 °C for 12 h. The obtained composite was then
subjected to heat treatment in argon at 600 °C for 2 h. For
a more complete filling of the hard template pores with the
substance after pyrolysis a second impregnation step of the
composite with melamine was performed using the same
procedure. The silica component was removed by treat-
ment of the obtained composites with 15% HF (Merck,
4
0%) solution for 12 h. Carbon nitride was filtered and
washed to a neutral pH value, and then dried at 100 °C. For
synthesis of N-doped carbon (С_M sample) the product of
bulk carbonization of sucrose at 900 °C for 2.5 h was used
as the initial material. For doping of the carbon structure
with nitrogen 3 g of the obtained carbon was treated with
ethanol solution of melamine (2 g of melamine in 10 mL
of ethanol) and stirred at a room temperature for 5 h. The
obtained suspension was boiled in order to evaporate alco-
hol and then the mixture was dried at 120 °C. The impreg-
nated carbon was heated in argon atmosphere up to 950 °C
2.2 Characterization
Phase composition of the samples was analyzed using
Bruker D8 Advance diffractometer equipped with Cu Kα
(λ=0.15406 nm) X-ray source, in the range of 2θ=3°–60°
at a scan rate of 1 deg/min.
(
heating rate 10 °C/min) and kept at this temperature for
Morphology of the samples was investigated using scan-
ning electron microscopy (SEM) with MIRA3 TESCAN
microscope at accelerating voltage of 5–20 kV.
0
.5 h. Then the sample was washed with hot distilled water
to neutral pH of wash water in order to remove any excess
of melamine decomposition products.
TEM images were obtained using the field emission TEM
JEM-2100 (JEOL) with an accelerating voltage of 100 kV.
The samples for TEM were ground in agate mortar with
ethanol, and then the suspension was deposited on a copper
grid coated with a carbon film.
In order to avoid significant changes in the chemical
nature of the support surface, ruthenium nanoparticles
were deposited using a mild reduction of the initial Ru pre-
cursor with a chemical reducing agent (hydrazine) similar
to an approach described in [30]. A weighted amount of
ruthenium trichloride (0.0409 g) (Merck, 99.98%), based
on the content in the composite of 5 wt%, was dissolved
Porous texture characterization of the carbon nitride and
carbon samples was carried out by nitrogen physisorption at
−196 °C using Sorptomatic 1990 after outgassing the sam-
ples at 200 °C under vacuum for 4 h. The total surface area,
1
3

N. D. Shcherban et al.
S
, was calculated using the BET equation [33]. Mesopore
well as 200 mg of catalyst. Before the reaction, the catalyst
was heated to 200 °C in an argon atmosphere for 60 min.
The samples were taken at different time intervals. Before
analysis of the samples by gas chromatography (GC), a sam-
ple of 0.5 ml was silylated using N,O-Bis(trimethylsilyl)
trifluoroacetamide, BSTFA (Acros, > 98%), 100 µl, and
trimethylchlorosilane, TMCS (Fluka, > 99%), 25 µl, and
pyridine (VWR Chemicals, >99%) 25 µl, respectively, at
70 °C for 1 h. The silylated reaction mixtures were ana-
lyzed with a gas chromatograph using HP-1 column (25 m,
200 µm, 0.11 µm) applying the following temperature pro-
gram: 120 °C (1 min)—6 °C/min—320 °С (15 min) and a
split ratio of 25:1. The injector temperature was 260 °C and
the detector temperature was 320 °C. The products were
confirmed by GC–MS using HP-5 column.
BET
size was determined using the Barrett–Joyner–Halenda
method from the desorption branch of the isotherm [34].
The micropore size was calculated according to the Hor-
vath–Kawazoe equation [35].
XPS-analysis of the samples was made using Perkin-
Elmer PHI 5400 spectrometer with a Mg K X-ray source
α
operated at 14 kV and 200 W. The samples were kept in the
preparation chamber of the XPS equipment overnight before
analysis. The pass energy of the analyzer was 17.9 eV and
the energy step 0.1 eV. The charging was adjusted according
to the C–C bond at 284.5 eV. Peak fitting was performed
with the program XPS Peak 4.1. The background was cor-
rected with the Shirley function.
Semi-quantitative analysis of metal concentrations was
performed using wavelength dispersive X-ray fluorescence
(
WDXRF) spectrometry with the powder pellet method.
Undiluted samples (0.5 g) were milled and put in the 29 mm
diameter die. The intensities of the metal lines in the samples
were measured in vacuum conditions on an ARL Advant’X
spectrometer equipped with a rhodium anode X-Ray tube.
Excitation conditions were as follows: tube voltage of 50 kV;
current of 40 mA; collimator with a divergence of 0.25°;
LiF200 crystal was used as a monochromator; scintillation
counter was used as a detector; counting time was 12 s. The
content of elements in the sample was estimated using a
semi-quantitative method by means of a QuantAS program
for standard-less analysis.
3 Results and Discussion
Pyrolysis of melamine leads to the formation of structures
with high-angle peaks (2θ~27.3–27.7°) on the X-ray diffrac-
tion patterns (Fig. 2) corresponding to the average interlayer
distance of d=0.327–0.322 nm similar to the (002) plane of
graphitic carbon nitride. The average crystallite sizes cal-
culated according to the broadening of (002) peak by the
Scherrer’s formula [37] are ca. 6–7 nm. Synthesized car-
bon, doped with nitrogen (C_M), is an amorphous material
because the corresponding X-ray diffraction pattern does not
contain any reflexes, including those ones characteristic for
the graphite structure.
The basicity of the tested materials was determined
by temperature programmed desorption of CO using a
2
Micromeritics Autochem 2910 equipment. Prior to adsorp-
According to SEM-images (Fig. 3a) carbon nitride
obtained by bulk pyrolysis consists of relatively large
monolithic particles (from 200 nm to a few microns). Car-
bon nitride prepared using silica template (C N –MCF) is
tion of CO a sample was heated to 400 °C (10 °C/min) in
2
a 10 ml/min flow of helium and kept at this temperature for
6
0 min. Thereafter, the sample was cooled to ambient tem-
3
4
perature and CO was adsorbed to the catalyst for 30 min
2
with a 50 ml/min flow. After CO adsorption the sample
2
was flushed with helium (20 ml/min) for 30 min to remove
500
400
300
200
100
0
physisorbed CO . The temperature programmed desorption
2
C N -1
3
4
was carried out with a 10 °C/min heating rate until 600 °C,
C N -2
the TCD signal was recorded every second.
3
4
C N -MCF
3
4
C_M
2
.3 Catalytic Tests
Betulin (90–94% purity) was extracted from birch with a
nonpolar solvent and recrystallised from 2-propanol fol-
lowing the literature procedure [36]. Betulin oxidation was
performed over synthesized Ru catalysts at a temperature of
1
40 °C and atmospheric pressure using a batch-mode oper-
10
20
30
40
50
60
ated glass reactor. Synthetic air (AGA, 20% oxygen, 80%
nitrogen) was used as an oxidant, mesitylene—as a solvent.
In a typical catalytic experiment, betulin oxidation was car-
ried out using 200 mg of reagent in 100 ml of solvent, as
2θ, deg., CuKα
Fig. 2 X-ray diffraction patterns of the obtained carbon nitride and
nitrogen-doped carbon samples
1
3

Preparation of Betulone Via Betulin Oxidation Over Ru Nanoparticles Deposited on Graphitic…
Fig. 3 SEM- and TEM-images of the obtained samples: SЕМ: a C N –1, b C N –MCF; TEM: c С_М
3
4
3
4
characterized by a more friable structure (Fig. 3b). Such
slightly more developed structure apparently can be due to
the presence of silica acting as a template during the ther-
mal treatment. N-doped carbon (С_М) is characterized by
a well-developed structure possessing slit-like micropores
with a size of ca. 0.5 nm (Fig. 3c).
pore volume testifying a high uniformity of microporous
structure in the obtained sample (Table 1).
Temperature-programmed desorption curves of carbon
dioxide (TPD CO ) from synthesized g-C N and nitrogen-
2
3
4
doped carbon samples contain one main maximum of carbon
dioxide desorption at ca. 130–160 °C (Fig. 4a). Deconvolu-
tion of the indicated curves (Fig. 7 b) using the Gaussian dis-
tribution function gives two main peaks with the temperature
maxima of carbon dioxide desorption at ca. 90–100 °C and
130–160 °C, which can be attributed to physisorption and
The textural characteristics of the prepared carbon
nitride and N-doped carbon calculated from nitrogen
adsorption–desorption isotherms are presented in Table 1.
C N –1 and C N –2 contain large mesopores (D
3
4
3
4
meso
4
0–50 nm). C N –MCF possesses smaller mesopores
adsorption of CO on weak basic sites, respectively. The cor-
3
4
2
(
D
ca. 30 nm) which can be associated with the pres-
responding concentrations of the basic sites without taking
meso
ence of the template in comparison with carbon nitride
into account the physically adsorbed carbon dioxide are ca.
prepared via traditional melamine bulk pyrolysis.
40–80 µmol/g (shoulder with the CO desorption maximum
2
Application of silica template (mesoporous cellular
foam MCF) results in some increase of carbon nitride
at 130–160 °C).
Deposition of ruthenium trichloride followed by reduc-
tion leads to formation of ruthenium nanoparticles with a
diameter ranging from 1 to 5 nm (Fig. 5) which is close
to the particle sizes obtained in [32]. It should be noted
that carbon nitride contributes to the formation of rela-
tively homogeneous nanoparticles (maxima of particle size
distribution are 1.7, 1.3, 4.0 and 1.6 nm for Ru–C N –1,
2
porosity, in particular BET specific surface area (22 m /g)
3
and pore volume (0.16 cm /g) compared to typical C N
3
4
2
3
(
10 m /g and 0.04 cm /g, respectively, Table 1). Com-
pletely mesoporous structures (without micropores) of the
prepared carbon nitride samples should be noted.
N-doped carbon (С_М) is a homogeneously micropo-
3
4
3
rous material with the micropore volume of 0.17 cm /g.
Ru–C N –2, Ru–C N –MCF and Ru–C_M, respectively,
3 4 3 4
Micropores (D
≤ 1 nm) constitute 85% of the total
Fig. 5), which can be connected with stabilizing effect of
the carbon nitride surface [38]. The average particle sizes
micro
Table 1 Structural-sorption
3
3
2
2
3
Sample
C N –1
Vmicrо, cm /g
Vmеsо, cm /g
Dmesо, nm
Smesо, m /g
SBET, m /g
Vads, cm /g
characteristics of supports (N ,
2
7
7 K)
0.003
–
–
0.04
0.06
0.16
–
38
~50
33
–
10
10
19
–
10
10
22
630
350
123
0.04
0.06
0.16
0.20
0.56
0.29
3
4
C N –2
3
4
C N –MCF
3
4
C_M
Sibunit
CNF-PI
0.17
1
3

N. D. Shcherban et al.
3
2
1
0
a
b
C N -1
2.5
2.0
1.5
1.0
0.5
0.0
3
4
C N -2
3
4
C N -MCF
3
4
C_M
100
200
300
400
0
100
200
300
400
Temperature,°C
Temperature,°C
Fig. 4 CO -TPD profiles for the prepared carbon nitride and carbon samples (a) and deconvolution for C N –MCF (b)
2
3
4
for Ru-CNF and Ru-Sib-Imp catalysts were 2.5 and 1.3 nm
respectively.
carbon. Betulone was the main desired product over the stud-
ied catalysts (selectivity up to 27%). The mass spectrum of
betulone is presented in SI. The peaks of by-products in
GC–MS are very small and therefore their identification is
very challenging. In general, by-products were represented
by several esters/ethers. Utilization of Ru-CNF prepared by
the colloidal method resulted in a much less active catalyst
forming mainly betulone (33% selectivity) while Ru-Sib-
Imp afforded higher conversion that Ru-CNF not, however,
comparable with Ru/carbon nitride catalysts. Selectivity
to betulinic aldehyde was at the same time the highest (ca.
15%) especially considering that conversion was lower for
Ru-Sib-Imp than in the case of Ru–C N (Table 2).
The chemical state of Ru in the obtained composites was
characterized by XPS (Fig. 6). Ru 3d XPS spectra (Fig. 6
a, b) consist of two main peaks at binding energies 280.7
and 280.2 eV assigned to Ru (4+) of the ruthenium oxide
(
RuO ) and the Ru (0) metal peak, respectively [39, 40].
2
Formed Ru particles being quite small (mainly 2–4 nm) are
exposed to surface oxidation, therefore resulting in the for-
mation of a core–shell structures [39]. In fact a high content
of Ru in a high oxidation state is observed even in classical
Ru/C catalysts and Ru/CNT after hydrogenation of sugars
[
41, 42]. Other peaks belong to C 1 s region of the sup-
3
4
port. In particular, two main peaks at 284.5 and 287.9 eV
Typical kinetic plots showing the main identified com-
ponents in the reaction mixture are presented in Fig. 7. As
can be seen from the kinetic curves Ru–C N –MCF allows
2
2
(
Fig. 6a, b) correspond to sp C–C bonds and sp -bonded
carbon in N-containing aromatic rings (N–C=N) [43]. Ru
p XPS spectra, compared to Ru 3d spectra, do not overlap
with other signals allowing monitoring the oxidation state
3
4
3
achieving a more rapid betulin transformation and forma-
tion of the reaction products (betulone, betulonic aldehyde,
betulonic acid, betulinic aldehyde, betulinic acid, lupeol) in
higher concentrations than Ru deposited on N-doped carbon
and undoped carbons. However faster formation of other
(unidentified) products should be noted which can be due
to an overall higher catalytic activity of Ru–C N –MCF
(
Fig. 6c, d). These spectra can be deconvoluted into three
peaks. The peak at a binding energy of 461.2 eV can be
attributed to Ru (0) from metal atoms, at 463.0–463.5 eV to
RuO and at 465.8–466.3 eV to RuO [39, 40].
2
x
Catalytic activity of Ru supported catalysts based on the
graphitic carbon nitride and N-doped carbon was tested in
the betulin oxidation with synthetic air. In order to compare
the influence of the support nature and porosity, Ru catalysts
supported on different undoped carbons (mesoporous Sibu-
nit and carbon nanofibers) were also investigated.
3
4
resulting in generation of side products together with the
desired ones. Application of Ru nanoparticles supported on
a conventional carbon support (Ru/C, Degussa) as a catalyst
results in a predominant formation of allobetulin (selectivity
72%, conversion 54%) which was assigned to acidic sites
inherent to the support [5]. Use of basic supports (i.e. car-
bon nitride and N-doped carbon) allows avoiding allobetulin
generation and it can be possibly responsible for higher oxi-
dation activity involving basic sites. Better catalytic perfor-
mance of Ru–C N –MCF in comparison with Ru-C N –1
Ru/carbon nitride possesses catalytic activity in betulin
oxidation higher than Ru/N-doped carbon (ca. 70% and 30%
conversion of betulin, respectively, Table 2). Probably, it
can be due to several reasons: (1) a significant fraction of
defects serving as active sites as well as presence of weak
Lewis basic sites on the surface of carbon nitride, (2) better
dispersion of the Ru nanoparticles and (3) more effective
mass transfer compared to only microporous Ru/N-doped
3
4
3
4
and Ru–C N –2 manifested in increased selectivity toward
3
4
the desired products (Table 2) can be associated with a bet-
ter developed porosity (Table 1) and reticulated structure
1
3

Preparation of Betulone Via Betulin Oxidation Over Ru Nanoparticles Deposited on Graphitic…
a
b
c
d
4
3
2
1
0
e
f
20
15
10
5
0
0
0
0
0
1
.0
1.5
2.0
2.5
3.0
0.75
1.00
1.25
1.50
1.75
2.00
Diameter, nm
Diameter, nm
g
h
2
5
0
5
0
5
0
20
15
10
5
0
2
1
1
2
3
4
5
6
1
2
3
4
5
Diameter, nm
Diameter, nm
Fig. 5 TEM-images and particle size distributions for the composites based on graphitic carbon nitride or nitrogen-doped carbon with ruthenium
nanoparticles: a, e Ru–C N –1, b, f Ru–C N –2, c, g Ru–C N –MCF, d, h Ru–C_M
3
4
3
4
3
4
1
3

N. D. Shcherban et al.
with a developed porosity (Ru-Sib-Imp) leads to an increase
of selectivity not only towards betulone, but also towards
another important product—betulinic aldehyde (Table 2).
There are available data in the literature on the prepa-
ration of betulone from betulin using microorganisms. For
example, the yield of betulone was up to 25% at 33 °C after
a
b
6
days [1]. Data on the preparation of betulone from betulin
using heterogeneous catalysts according to our knowledge
are absent. The maximal yield of betulone achieved in the
current study is ca. 14% after 3 h using Ru–C N –MCF as
3
4
the catalyst. The obtained data can be used for further inves-
tigation and improvement of the catalytic performance of Ru
supported heterogeneous catalysts in betulin oxidation to
useful pharmaceutical products including betulone.
2
94 292 290 288 286 284 282 280 278 276
294 292 290 288 286 284 282 280 278 276
Binding energy, eV
Binding energy, eV
c
d
It should be noted that, as a result of catalytic experi-
ments, the reaction mixture became yellow, which according
to GC–MS data was due to partial oxidation of the solvent
(
mesitylene) to 3,5-dimethylbenzoic acid.
High oxidative activity of the prepared materials and
formation of betulone can be associated with the presence
of RuO in the nanoparticles, which in accordance with
2
[
39] is extremely active for CO oxidation. The size effect
of catalytic activity for Ru nanoparticles within the 2–7 nm
size range was correlated with the stability of the core–shell
structure [44].
472 470 468 466 464 462 460 458 456
472 470 468 466 464 462 460 458 456
Binding energy, eV
Binding energy, eV
Fig. 6 XPS spectra of Ru 3d (a, b) and Ru 3p (c, d) regions for Ru–
C N –2 (a, c) and Ru–C_M (b, d)
4
Conclusions
3
4
Ru nanoparticles were deposited on graphitic carbon nitride,
N-doped carbon and mesoporous carbons. It has been shown
that Ru supported on a hard-templated carbon nitride exhib-
ited higher catalytic activity in the betulin oxidation than
Ru/N-carbon composites, which can be probably attributed
to a significant fraction of weak basic sites required for oxi-
dation. Formation of betulone as the main desired reaction
product (selectivity up to 27% with the yield reaching ca.
14% after 3 h) over heterogeneous Ru supported catalysts
was demonstrated.
(
Fig. 4c) of Ru–C N –MCF obtained via the hard-templating
3 4
method.
Selectivity towards betulone as a function of betulin
conversion presented in Fig. 8, contains maxima, testifying
probably intensification of the side products formation.
Comparing the catalytic results it can be suggested that
the presence of weak basic sites in the structure of the sup-
port (carbon nitride and N-doped carbon) increases the bet-
ulin conversion, while application of the carbon supports
Table 2 Catalytic behaviour
Catalyst
X (%)
S1 (%)
S2 (%)
S3 (%)
S4 (%)
S5 (%)
Y (%)
1
of Ru containing catalysts in
betulin oxidation
Ru–C N –1
82.6
72.9
67.3
30.7
6.7
9.8
7.2
23.4
27.4
33.3
19.5
1.2
0
8.5
0.9
4.2
9.4
2.8
2.7
4.4
4.4
0.1
1.0
1.3
3.6
8.6
6.0
12.8
14.9
4.0
8.9
1.5
3.6
0
8.1
5.3
12.8
8.4
2.2
7.7
3
4
Ru–C N –2
3
4
Ru–C N –MCF
3
4
Ru–C_M
Ru–CNF
Ru-Sib-Imp
39.4
4.1
X conversion of betulin after 4 h (%), S selectivity to betulone (%), S selectivity to betulonic aldehyde
1
2
(
%), S selectivity to betulonic acid (%), S selectivity to betulinic aldehyde (%), S selectivity to betulinic
3
4
5
acid (%), Y (%) yield of betulone (%)
1
1
3

Preparation of Betulone Via Betulin Oxidation Over Ru Nanoparticles Deposited on Graphitic…
Fig. 7 Kinetics of betulin oxida-
tion over Ru–C N –MCF (a),
a
b
3
4
4
3
2
1
0
4
3
2
1
0
Ru–C_M (b) and Ru-Sib-Imp
betulin
betulone
(
c)
betulin
betulone
betulonic aldehyde
betulonic acid
betulinic aldehyde
betulinic acid
lupeol
betulonic aldehyde
betulonic acid
betulinic aldehyde
betulinic acid
lupeol
other
other
0
60
120
180
240
0
60
120
180
240
Time, min
Time, min
c
5
betulin
betulone
4
3
2
1
0
betulonic aldehyde
betulonic acid
betulinic aldehyde
betulinic acid
other
0
60
120
180
240
Time, min
biologically active substances for pharmaceutics) of the State Founda-
tion for Fundamental Research.
Ru-C_M
4
3
2
1
0
0
0
0
0
Ru-C N -MCF
3
4
Compliance with Ethical Standards
Conflict of interest The authors declare no conflict of interest.
OpenAccess This article is distributed under the terms of the Crea-
tive Commons Attribution 4.0 International License (http://creativeco
mmons.org/licenses/by/4.0/), which permits unrestricted use, distribu-
tion, and reproduction in any medium, provided you give appropriate
credit to the original author(s) and the source, provide a link to the
Creative Commons license, and indicate if changes were made.
0
10
20
30
40
50
60
70
Conversion of betulin,%
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