Heterogeneous Catalytic Synthesis of Zingerone and Dehydrozingerone

Article abstract of DOI:10.1134/S0965544120090066

Abstract: Results of a single-stage heterogeneous catalytic synthesis of zingerone and dehydrozingerone have been described. The prospects of the proposed approach have been shown; the main kinetic laws governing the reaction have been revealed. Optimum conditions for zingerone and dehydrozingerone synthesis providing a yield of the target products of 45.8 and 76.2%, respectively, have been found.

Full text of DOI:10.1134/S0965544120090066

ISSN 0965-5441, Petroleum Chemistry, 2020, Vol. 60, No. 9, pp. 1080–1086. © Pleiades Publishing, Ltd., 2020.
Russian Text © The Author(s), 2020, published in Neftekhimiya, 2020, Vol. 60, No. 5, pp. 693–700.
Heterogeneous Catalytic Synthesis
of Zingerone and Dehydrozingerone
P. A. Chistyakovaa, *, A. V. Chistyakova, and M. V. Tsodikova
aTopchiev Institute of Petrochemical Synthesis, Russian Academy of Sciences, Moscow, 119071 Russia
*e-mail: polina.zharova@mail.ru
Received March 26, 2020; revised May 5, 2020; accepted May 12, 2020
Abstract—Results of a single-stage heterogeneous catalytic synthesis of zingerone and dehydrozingerone
have been described. The prospects of the proposed approach have been shown; the main kinetic laws gov-
erning the reaction have been revealed. Optimum conditions for zingerone and dehydrozingerone synthesis
providing a yield of the target products of 45.8 and 76.2%, respectively, have been found.
Keywords: heterogeneous catalysis, copper, dehydrozingerone, zingerone
DOI: 10.1134/S0965544120090066
Zingerone and dehydrozingerone are biologically rhea is the main cause of infant mortality in develop-
active substances constituting ginger root [1]. These
substances are commonly used in the food industry (as
flavorings and conserving agents [2]) and the pharma-
ceutical industry: dehydrozingerone is used as an
active component of anticonvulsants, an antioxidant,
and an antimutagenic agent [3], while zingerone is an
antioxidant and an antiinflammatory agent and exhib-
its activity in the suppression of enterotoxins (Esche-
ing countries [6]).
Zingerone and dehydrozingerone were first iso-
lated from ginger root by Japanese chemist Hiroshi
Nomura in 1917 [7]. In addition, Nomura has devel-
oped a synthetic method for zingerone synthesis by the
hydrogenation of dehydrozingerone derived by the
condensation of acetone and vanillin in the presence
richia coli) that cause diarrhea [4, 5] (this type of diar- of alkalis (Scheme 1).
OH OH
OH
O
O
O
CH3
CH3
CH3
CH3
CH3
NaOH
+H2
H3C
CH3
+
−H2O
O
OH
O
O
Dehydrozingerone
Scheme 1. Two-stage synthesis of zingerone.
Zingerone
Zingerone is still [8] produced by the two-stage used to synthesize zingerone from vanillin and isopro-
method proposed by Nomura with the use of alkalis,
which significantly increases the amount of waste and
the cost of production [9]. Currently, attempts are
being made to search for effective heterogeneous cata-
lysts for the production of dehydrozingerone by the
condensation of acetone with vanillin. A promising
catalyst for the process is hydrotalcite, in the presence
panol in a single stage. A single-stage synthesis in the
presence of supported catalysts will make it possible to
exclude the hydrogenation stage and abandon the use
of alkali at the first stage of condensation of vanillin
with acetone.
This study is focused on the development of het-
of which the dehydrozingerone yield achieves 88% erogeneous catalytic methods to produce valuable bio-
within 4 h of the reaction [3].
logically active substances by the alkylation of vanillin
with acetone or isopropanol. Results of a single-stage
heterogeneous catalytic synthesis of zingerone and
It was previously found that primary alcohols can
undergo heterogeneous catalytic cross-condensation
with secondary alcohols [10]. This approach can be dehydrozingerone are described. Prospects of the pro-
1080

HETEROGENEOUS CATALYTIC SYNTHESIS
1081
posed approach are shown; the main kinetic laws gov- (5 min), 10 deg/min, 280°C , Tinj = 250°С, Pinj = 1
erning the reactions are revealed.
bar, split ratio of 1/200, a flame ionization detector).
The acidic properties of the catalysts were studied
by temperature-programmed desorption (TPD) of
ammonia, which is used as a probe molecule, on an
USGA gas chemisorption analyzer. A catalyst with a
fraction of 0.25–0.5 mm and a weight of ~0.1 g
(weighed portion was taken at an accuracy of 5 × 10–4 g)
was placed in a quartz reactor on a layer of silica with
a fraction of 1–0.5 mm. The sample was heated in a
helium stream to a temperature of 500°С at a rate of 15
deg/min and calcined at this temperature in a helium
stream for 1 h; after that, it was cooled to a tempera-
ture of 60°С. Next, the sample was saturated with
ammonia in a stream of dried ammonia diluted with
nitrogen for 20 min. Physically adsorbed ammonia
was removed at 100°С in a dry helium stream for 1 h.
After that, the sample was rapidly cooled in a dry
helium stream (30 mL/min) to a temperature of 60°С.
Analysis conditions: temperature increase to 600°C at
a rate of 8°C/min in a helium stream at a flow rate of
30 mL/min.
EXPERIMENTAL
Catalytic tests for the cross-condensation of vanil-
lin with acetone and isopropanol in the presence of the
synthesized systems were conducted on a Parr Series
5000 multiple reactor autoclave system. The test time
under steady-state conditions was 5 h; stirring was
implemented with a magnetic stirrer at a speed of
1000 rpm; the gas in the autoclave volume was argon
under an initial pressure of 1 atm. Acetone and isopro-
panol were taken in a 15-fold molar excess with respect
to vanillin.
Mono- and bimetallic catalysts Cu/Al2O3,
Ni/Al2O3, Ni–Cu/Al2O3, Fe–Cu/Al2O3, and Co–
Cu/Al2O with a metal content of 1 wt % were prepared
by incipient wetness impregnation from solutions
of respective nitrates (reagent grade); the support was
γ-Al2O3 (AO Angarsk Plant of Catalysts and Organic
Synthesis, 160 m2/g, 0.5-mm pellets). The synthesized
samples were dried in a vacuum at 80°C for 5 h and
then calcined in a muffle furnace at 500°C in an argon
atmosphere for 5 h.
RESULTS AND DISCUSSION
The laws governing the occurrence of two reac-
tions—the condensation of vanillin and acetone
(Scheme 2, reaction (1)) and vanillin and isopropanol
(Scheme 2, reaction (2))—were studied. The catalysts
were mono- and bimetallic systems based on γ-Al2O3
with supported copper particles and the iron triad
metals, which previously proved to be highly active
and selective in the condensation of oxygen-contain-
The qualitative composition of the liquid organic
products was determined by chromatography–mass
spectrometry on an Agilent MSD 6973 (HP-5MS col-
umn) and DelsiNermag Automass-150 instruments
(CPSil-5 column) at an electron ionization of EI =
70 eV. The quantitative content of the liquid organic
substances was determined by gas–liquid chromatog-
raphy on a Varian 3600 instrument (Chromatec col-
umn, SE-30, 0.25 × 250 cm, Df = 0.3 mm, 50°C ing compounds [11–13]:
OH OH
O
O
CH3
CH3
CH3
cat.
−H2O
H3C
OH
CH3
+
(1)
(2)
O
OH
O
OH
OH
H3C
CH3
OH
H3C
CH3
O
O
O
CH3
CH3
CH3
CH3
CH3
cat.
+H2
cat.
−H2O
кат.
−H2
+
O
OH
O
O
Scheme 2. Condensation of (1) vanillin with acetone to produce dehydrozingerone
and (2) vanillin with isopropanol to produce zingerone.
Figure 1 shows dependences of vanillin conversion catalysts based on iron and cobalt exhibit a signifi-
at a fixed temperature (180°C) on the nature of the cantly lower activity in the dehydrozingerone and zin-
supported metals. It is evident from the data in the fig- gerone synthesis reactions; therefore, Ni/Al2O3 and
ure that the most active metals are copper and nickel,
which provide the maximum vanillin conversion. The
Сu/Al2O3 catalysts were selected for further studies.
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CHISTYAKOVA et al.
Zingerone
100
90
80
70
60
50
40
30
20
10
0
Dehydrozingerone
Fe
Co
Ni
Cu
Fig. 1. Vanillin conversion in the studied reactions in the presence of monometallic catalysts at a temperature of 180°C and a con-
tact time of 3 h.
The temperature dependences of the dehydrozing- in the presence of the Cu/Al2O3 catalyst, the target
erone and zingerone yields achieved during the con-
densation of vanillin with isopropanol and vanillin
with acetone, respectively, are listed in Table 1.
product yield is more than 10% higher than the yield
obtained in the presence of the Ni/Al2O3 catalyst (at
245°C).
It was found that the optimum temperature for
dehydrozingerone synthesis is 180°C; it provides a
maximum product yield in the presence of the studied
catalysts. In the presence of the Ni/Al2O3 catalyst, the
dehydrozingerone yield is more than 10% higher than
the yield achieved in the presence of the Cu/Al2O3 cat-
alyst (at 180°C); this fact indicates a higher activity of formation of resinous nonvolatile compounds, which
the nickel-containing system. However, an opposite apparently are products of the polycondensation of
picture is observed during the synthesis of zingerone: vanillin and acetone (Scheme 3).
It is significant that, at temperature of 180°C, the
zingerone yield is 40–50% lower than the dehydrozin-
gerone yield; this fact apparently suggests that the
reactions have different rate-limiting steps. With an
increase in temperature to 245°C, the dehydrozinge-
rone yield abruptly decreases owing to the vigorous
OH
CH3
O
O
CH3
...
CH3
O
HO
H3C
O
Scheme 3. Probable dehydrozingerone polycondensation route.
In the presence of the Cu/Al2O3 catalyst, an vanillin and isopropanol was the Cu/Al2O3 catalyst, in
increase in temperature to 245°C leads to a 10% the presence of which the maximum zingerone yield of
increase in the yield of zingerone synthesized from 45.8% at 245°C was achieved (Table 1).
vanillin and isopropanol. In the presence of the
Ni/Al2O3 catalyst, an increase in temperature
increases the zingerone yield only slightly; in this case,
the content of resinous nonvolatile compounds in the
reaction products increases.
Thus, it was found that the most active catalyst of
the samples studied in dehydrozingerone synthesis
was the Ni/Al2O3 catalyst providing the target product
Taking into account the fact that the catalyst sys-
tems tested in this study are supported catalysts, cata-
lytic tests on the determination of the catalytic activity
of the support (γ-Al2O3) were conducted (Table 2). It
is evident from Table 2 that alumina is active in the
conversion of acetone and vanillin to dehydrozinge-
rone and almost inactive in the conversion of isopro-
panol and vanillin to zingerone. In the presence of alu-
yield of more than 87% at a temperature of 180°C. The mina, the dehydrozingerone yield is lower than that in
most promising catalyst for zingerone synthesis from the presence of the metal-containing catalysts. At the
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HETEROGENEOUS CATALYTIC SYNTHESIS
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Table 1. Temperature dependence of the dehydrozingerone and zingerone yields in the case of catalysis with 1 wt %
Cu/Al2O3 and 1 wt % Ni/Al2O3 systems
Cu/Al2O3
Ni/Al2O3
Cu/Al2O3
Ni/Al2O3
Catalyst
temperature, °С
dehydrozingerone yield, %*
zingerone yield, %**
130
180
245
16.0
76.2
20.4
18.1
87.5
17.3
4.2
36.3
45.8
1.5
31.6
35.2
* Dehydrozingerone is synthesized by reaction (1) shown in Scheme 2.
** Zingerone is synthesized by reaction (2) shown in Scheme 2.
same time, the variation in the dehydrozingerone yield
To determine the acidic properties of the studied
in the presence of Al2O3 exhibits a symbatic depen- catalysts, ammonia TPD studies were conducted;
their results are shown in Fig. 2. It is evident from
Fig. 2 that the alumina surface is capable of adsorbing
a significantly larger number of ammonia probe mol-
ecules; this finding indicates the presence of a larger
number of acid sites on the alumina surface. The
Sibunit-based catalyst has hardly any ability to adsorb
ammonia. Thus, the above assumption of the depen-
dence of the catalyst activity in the condensation of
acetone with vanillin to dehydrozingerone on the cat-
alyst acidity is fully confirmed in the studies.
The next stage of the study was analysis the laws
governing the synthesis of zingerone and dehydrozin-
gerone in the presence of bimetallic catalysts. The use
of bimetallic catalysts is a potentially promising field
of catalysis, because different pairs of metals can
dence, which is shown in Table 1 for the supported
catalysts. This fact suggests that a key factor in the
condensation of acetone and vanillin is the acidity of
the catalyst surface, whereas condensation is not the
rate-limiting step for zingerone synthesis. It should be
noted that, according to Scheme 2, one of the initial
stages of zingerone synthesis is isopropanol dehydro-
genation to acetone, which is apparently complicated
in the presence of alumina without metal components.
In addition, the main route of isopropanol conversion
in the presence of unmodified alumina is isopropanol
dehydration into propylene and diisopropyl ether. On
the other hand, the low activity of alumina in zinge-
rone synthesis can be attributed to the competing
chemisorption of isopropanol and vanillin.
It is known that an important factor affecting the exhibit a synergistic effect, which consists in an abrupt
occurrence of chemical reactions is catalyst acidity increase in their catalytic activity and/or selectivity in
[14–16]. To verify the effect of the acid–base proper- chemical reactions [17].
ties of the support on the parameters of the studied
The catalytic test results showed that the introduc-
reactions, catalytic tests on the synthesis of zingerone
tion of iron or cobalt into the Cu/Al2O3 system leads to
and dehydrozingerone in the presence of catalysts
a decrease in catalytic activity in the synthesis of both
based on Sibunit and silica were conducted (Table 3).
dehydrozingerone and zingerone (Fig. 3). The use of a
It was found that, in the presence of the silica-
based catalyst, the zingerone and dehydrozingerone
yield abruptly decreases, while the Sibunit-based cat-
alyst exhibits hardly any catalytic activity. Taking into
account the surface factor, in this study, catalyst sup-
ports with a specific surface area that was close to or
larger than the specific surface area of alumina (180–
230 m2/g) were tested (250–300 and 380–430 m2/g for
SiO2 and Sibunit, respectively). Thus, the decrease in
catalytic activity in the order Cu/Al2O3 > Cu/SiO2 >
Cu/C is most probably attributed to a change in the
surface acidity.
Ni–Cu/Al2O3 bimetallic system with different ratios
of active components for the condensation of vanillin
with acetone does not lead to visible changes in activ-
ity; moreover, the monometallic nickel catalyst exhib-
its a nearly identical activity. Thus, a key factor in
dehydrozingerone synthesis from vanillin and acetone
is, apparently, the acidity of the catalyst support. The
deposition of nickel particles by the impregnation of
alumina with nickel nitrate and subsequent calcining
can lead to the formation of surface NixAl2xO4 mixed
oxide particles, which, in turn, can form a favorable
acidity region for the occurrence of the condensation
reaction. It should be noted that the ammonia TPD
curves of “pure” alumina and alumina with deposited
nickel particles are almost identical; this factor com-
plicates the further analysis by this method.
Table 2. Dehydrozingerone and zingerone yield in the
presence of an Al2O3 catalyst support at a test time of 3 h
Dehydrozingerone
In the case of using bimetallic systems for zinge-
rone synthesis, it was found that the maximum target
product yield is achieved in the presence of the Cu–
Ni/Al2O3 system at a 1 : 1 molar ratio of components
(Fig. 3). There is a large amount of published data on
the formation of copper and nickel alloys on the sur-
Temperature, °С
Zingerone yield, %
yield, %
130
180
245
4.9
33.3
13.6
0.0
0.0
0.1
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CHISTYAKOVA et al.
Table 3. Dehydrozingerone and zingerone yield in the presence of catalysts based on the different supports
Temperature
catalyst
180°С
Temperature
catalyst
245°С
dehydrozingerone yield, %
zingerone yield, %
Ni/Al2O3
Cu/Al2O3
87.5
13.7
0.4
45.8
9.4
0.1
Ni/SiO2
Ni/C
Cu/SiO2
Cu/C
face of porous supports [18–20]. In general, the
Calculations of the recorded kinetic curves showed
main factor affecting the catalytic properties of alloys that, for the condensation of vanillin with isopropanol
is the electronic factor, i.e., a change in the energy of and vanillin with acetone, a pseudo-zero and pseudo-
the d-band of the alloy compared with that of the indi- first order of reaction with respect to vanillin, respec-
vidual metals [21].
tively, is observed. The data suggest that, in the case of
the condensation of vanillin with acetone, vanillin
and, apparently, acetone are chemisorbed by the cata-
lyst surface; after that, they undergo a chemical reac-
tion. In the reaction of vanillin with isopropanol, the
pseudo-first order of reaction with respect to vanillin
suggests that a probable rate-limiting step is isopropa-
nol dehydrogenation on the catalyst surface.
The results show that, in the condensation of ace-
tone with vanillin and isopropanol with vanillin, the
main factor is the acidity of the catalyst and the hydro-
genation–dehydrogenation activity of the supported
active components, respectively. To confirm this con-
clusion, a kinetic analysis of the reactions was con-
ducted to determine the apparent activation energies
and compare them.
The activation energy and preexponential factor for
the studied reactions were calculated. In the synthesis
of dehydrozingerone, the apparent activation energy
Figure 4 shows the kinetic curves of the conversion
of vanillin reacting with isopropanol in the presence of was 80.3 kJ/mol and the preexponential factor was
1.3 × 106. In the synthesis of zingerone, the apparent
a Ni–Cu/Al2O3 catalyst (initial vanillin concentration
of 0.1 mol/L, 13-fold molar excess of isopropanol). activation energy was 92.4 kJ/mol and the preexpo-
nential factor was 7.8 × 107. The calculated activation
energy values also indicate a high probability of differ-
ent rate-limiting steps in the alkylation of vanillin with
acetone or isopropanol.
Figure 5 shows the kinetic curves of the conversion of
vanillin reacting with acetone in the presence of a Ni–
Cu/Al2O3 catalyst (initial vanillin concentration of
0.1 mol/L, 13-fold molar excess of acetone).
800
700
600
500
400
300
200
100
0
50
100
150
200
250
300
350
400
450
500
Temperature, °С
Fig. 2. Temperature dependence of ammonia desorption rate for alumina, silica, and Sibunit.
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HETEROGENEOUS CATALYTIC SYNTHESIS
Dehydrozingerone yield Zingerone yield
1085
100
90
80
70
60
50
40
30
20
10
0
Fig. 3. Yield of dehydrozingerone (at 180°C) and zingerone (at 245°C) in the presence of bimetallic catalysts at a test time of 3 h.
0.100
0.095
0.090
0.085
0.080
463 К
483 К
0.075
503 К
0.070
1000
2000
3000
Time, s
4000
5000
6000
0
Fig. 4. Kinetic curves of the conversion of vanillin reacting with isopropanol in the presence of a Ni–Cu/Al O catalyst (initial
2
3
vanillin concentration of 0.1 mol/L, 13-fold molar excess of isopropanol).
CONCLUSIONS
nol, a fundamental role is played by the hydrogena-
tion–dehydrogenation activity of the copper-contain-
ing active components. Kinetic studies have revealed
the order of the studied reactions with respect to van-
illin and the apparent activation energies. For the con-
densation of vanillin with acetone and vanillin with
isopropanol, the apparent activation energy is 80.3
and 92.4 kJ/mol, respectively. The increase in the
apparent activation energy for the condensation of
vanillin with isopropanol is apparently attributed to a
change of the rate-limiting step for another, which is
characterized by a higher activation barrier to the reac-
The studies have shown the possibility of imple-
menting the heterogeneous catalytic alkylation of van-
illin with isopropanol and acetone to produce zinge-
rone and dehydrozingerone, which are valuable bio-
logically active substances constituting ginger root. It
has been shown that nickel–copper catalysts are
highly promising for a single-stage synthesis of zinge-
rone from vanillin and isopropanol, without using
alkalis and solvents. It has been found that, in the con-
densation of vanillin with acetone, the main factor
affecting the catalyst activity is the catalyst acidity,
while in the condensation of vanillin with isopropa- tion.
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1086
CHISTYAKOVA et al.
0.095
0.085
0.075
0.065
0.055
0.045
0.035
393 К
408 К
423 К
1000
2000
3000
Time, s
4000
5000
6000
0
Fig. 5. Kinetic curves of the conversion of vanillin reacting with acetone in the presence of a Ni–Cu/Al O catalyst (initial vanillin
2
3
concentration of 0.1 mol/L, 13-fold molar excess of isopropanol).
FUNDING
9. Z. Wang, G. Yin, J. Qin, et al., Synthesis 2008, 3675
(2008).
This work was supported by the Russian Foundation for
Basic Research, project no. 18-33-01068.
10. A. V. Chistyakov, P. A. Zharova, S. A. Nikolaev, and
M. V. Tsodikov, Catal. Today 279, 124, (2017).
11. A. V. Chistyakov, S. A. Nikolaev, P. A. Zharova, et al.,
CONFLICT OF INTEREST
Energy 166, 569 (2019).
12. P. A. Zharova, A. V. Chistyakov, M. V. Tsodikov, et al.,
The authors declare that there is no conflict of interest
regarding the publication of this manuscript.
Chem. Eng. Trans. 57, 31 (2017).
13. P. A. Zharova, A. V. Chistyakov, M. V. Tsodikov, et al.,
Chem. Eng. Trans. 50, 295 (2016).
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