Pt-Catalyzed selective oxidation of alcohols to aldehydes with hydrogen peroxide using continuous flow reactors

Article abstract of DOI:10.1039/d0ob02213f

The oxidation of alcohols to aldehydes is a powerful reaction pathway for obtaining valuable fine chemicals used in pharmaceuticals and biologically active compounds. Although many oxidants can oxidize alcohols, only a few hydrogen peroxide oxidations can be employed to continuously synthesize aldehydes in high yields using a liquid-liquid two-phase flow reactor, despite the possibility of the application toward a safe and rapid multi-step synthesis. We herein report the continuous flow synthesis of (E)-cinnamaldehyde from (E)-cinnamyl alcohol in 95%-98% yields with 99% selectivity for over 5 days by the selective oxidation of hydrogen peroxide using a catalyst column in which Pt is dispersed in SiO₂. The active species for the developed selective oxidation is found to be zero-valent Pt(0) from the X-ray photoelectron spectroscopy measurements of the Pt surface before and after the oxidation. Using Pt black diluted with SiO₂as a catalyst to retain the Pt(0) species with the optimal substrate and H₂O₂introduction rate not only enhances the catalytic activity but also maintains the activity during the flow reaction. Optimizing the contact time of the substrate with Pt and H₂O₂using a flow reactor is important to proceed with the selective oxidation to prevent the catalytic H₂O₂decomposition.

Full text of DOI:10.1039/d0ob02213f

Organic &
Biomolecular Chemistry
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PAPER
Pt-Catalyzed selective oxidation of alcohols to
aldehydes with hydrogen peroxide using
continuous flow reactors†
Cite this: Org. Biomol. Chem., 2021,
19, 1115
a
Yoshihiro Kon, *a Takuya Nakashima,a Akira Yada, a Tadahiro Fujitani,
a
Shun-ya Onozawa,a Shū Kobayashi
*
a,b and Kazuhiko Sato
*
The oxidation of alcohols to aldehydes is a powerful reaction pathway for obtaining valuable fine chemi-
cals used in pharmaceuticals and biologically active compounds. Although many oxidants can oxidize
alcohols, only a few hydrogen peroxide oxidations can be employed to continuously synthesize aldehydes
in high yields using a liquid–liquid two-phase flow reactor, despite the possibility of the application
toward a safe and rapid multi-step synthesis. We herein report the continuous flow synthesis of (E)-cinna-
maldehyde from (E)-cinnamyl alcohol in 95%–98% yields with 99% selectivity for over 5 days by the selec-
tive oxidation of hydrogen peroxide using a catalyst column in which Pt is dispersed in SiO2. The active
species for the developed selective oxidation is found to be zero-valent Pt(0) from the X-ray photo-
electron spectroscopy measurements of the Pt surface before and after the oxidation. Using Pt black
diluted with SiO2 as a catalyst to retain the Pt(0) species with the optimal substrate and H2O2 introduction
rate not only enhances the catalytic activity but also maintains the activity during the flow reaction.
Optimizing the contact time of the substrate with Pt and H2O2 using a flow reactor is important to
proceed with the selective oxidation to prevent the catalytic H2O2 decomposition.
Received 6th November 2020,
Accepted 27th December 2020
DOI: 10.1039/d0ob02213f
rsc.li/obc
only application to tandem reactions, but also improvement in
the selectivity of aldehyde formation by adjusting the contact
Introduction
The selective oxidation of alcohols to obtain their corresponding time of the substrate with H2O2 and catalyst. Many environmen-
aldehydes is a central issue in the synthesis of various fine tally benign oxidation reactions use flow reactors in the pres-
chemicals used in pharmaceuticals and biologically active com- ence of catalysts, with water being the co-product.6,7 For
pounds.1 Many reports exist on the selective oxidation of alco- example, RuO2/Mn3O4, Au–Pd/TiO2, Au-doped FenOm particles,
hols using heavy metals containing oxidants and hypervalent Au–Pd nanoparticles, Ru(OH)x/Al2O3, and biocatalysts in the
iodide oxidants.1a,2 These oxidants allow the syntheses of alde- presence of O2 and Br− with H2SO4 and a phase transfer catalyst
hydes in high yields, but their by-products include heavy metals with polyoxometalates in the presence of H2O2 have been
and iodide compounds, which are harmful to the environ- reported.6 In particular, some of them can also oxidize allylic
ment.3 Although H2O2 is a clean oxidant that forms only water alcohols to obtain α,β-unsaturated aldehydes.7 However, no
after oxidation, it is less reactive and thus needs an appropriate examples exist on long-term oxidation using a flow reactor for
catalyst to accelerate the oxidation.4 Recently, flow reactors have several days in the presence of environmentally friendly oxi-
been frequently applied to produce valuable compounds that dants such as O2 and H2O2.6,7 Although H2O2 offers the advan-
are useful as pharmaceuticals.5 The use of flow reactors for tage of being easier to activate than O2, its disadvantage is that
selective H2O2 oxidation reactions offers the advantages of not it is an explosive oxidant.6b Various solid catalysts for selective
H2O2 oxidation in batch processes have been reported.8 We
selected Pt black as an excellent candidate for the selective syn-
aInterdisciplinary Research Center for Catalytic Chemistry,
thesis of α,β-unsaturated aldehydes because the oxidation pro-
ceeded significantly fast.9 However, mixing Pt and H2O2 in a
National Institute of Advanced Industrial Science and Technology (AIST), Tsukuba,
flask results in immediate H2O2 decomposition9,10 thereby
Ibaraki 305-8565, Japan. E-mail: y-kon@aist.go.jp, k.sato@aist.go.jp
bDepartment of Chemistry, School of Science, The University of Tokyo, Hongo,
making it difficult to control the contact between Pt and H2O2
Bunkyo-ku, Tokyo 113-0033, Japan. E-mail: shu_kobayashi@chem.s.u-tokyo.ac.jp
to achieve selective H2O2 oxidation.9 Flow synthesis is one of
†Electronic supplementary information (ESI) available. See DOI: 10.1039/
the best choices for controlling the contact time of Pt and H2O2
d0ob02213f
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Table 1 Screening of catalysts regarding the oxidation of 1
with substrates by adjusting the flow rate, H2O2 concentration,
substrate concentration, and reaction temperature.
Entry
Catalysts
Time (min.)
Conv. of 1a (%)
Yield of 2a (%)
Herein, we report the continuous selective oxidation of
useful alcohols, including aliphatic, benzyl, and allylic alco-
hols, by a continuous flow method. The optimized reaction
conditions using a catalyst in which Pt black was dispersed in
SiO2 (i.e., Pt + SiO2), in the presence of H2O2, enabled the oxi-
dation of (E)-cinnamyl alcohol (1) to (E)-cinnamaldehyde (2) in
more than 95% yield with excellent selectivity while retaining
high reactivity for over 5 days. The surprisingly well-preserved
catalytic activity of Pt during the reaction was studied through
substrate screening and oxidation state measurements by X-ray
1
2
3
4
5
6
7
8
9
Pt + Al2O3
Pt + Al2O3
Pt + Al2O3
Pt + MgO
Pt + MgO
Pt + MgO
Pt + SiO2
Pt + SiO2
Pt + SiO2
15
30
60
15
30
60
15
30
60
13
12
12
7
6
5
22
19
18
13
12
12
7
6
5
22
19
18
Reaction conditions: 10 mg of Pt black, 990 mg of metal oxide, 1 mol
L
−1 of 1 in t-amylOH solution, 6 wt% aq. H2O2, 90 °C reaction tempera-
photoelectron spectroscopy (XPS). The appropriate flow rate of ture, and 0.3 ml min−1 flow rate. Conversions and yields were exam-
ined by sampling at 15, 30, and 60 min. a Determined by gas chromato-
the reactants and H2O2 to optimize the contact time with the
Pt + SiO2 catalyst maintains zero-valent Pt (Pt(0)) at the Pt
graphy (GC) analysis based on 1.
black surface, which is crucial for selective H2O2 oxidation.
cation of the Pt black catalyst itself to a flow rector column
seems to be dangerous because it causes the explosive
Results and discussion
Screening of catalysts in the Pt-catalyzed H2O2 oxidation of (E)-
decomposition of H2O2.6b,9 An optimal catalyst was thus
required to avoid the explosive decomposition of H2O2 and the
aggregation of Pt black. Upon using TiO2 and CeO2 to dilute Pt
black individually, the flow stopped owing to the small par-
ticles of TiO2 and CeO2. Al2O3 and MgO also did not show
good reactivity (Table 1). Al2O3 was known to coordinate with
Pt because of its low binding energy (BE) toward the O atom in
the support, which would affect the oxidation state of Pt.11
MgO worked as a solid base catalyst and facilitated H2O2
decomposition. In the case of using a mixture of Pt black and
SiO2 (1 : 99 w/w, ca. 1.0 g), a clear improvement in the catalytic
activity was observed to obtain (E)-cinnamaldehyde (2) in up to
22% yield. The TOF value (h−1) of the Pt catalyst was calculated
to be 77.12 We used a mixture of Pt black and SiO2 for the fol-
lowing flow oxidation reactions.
cinnamyl alcohol (1)
(E)-Cinnamyl alcohol (1) was selected as a test sample for the
selective oxidation of alcohols because it is a less-reactive
alcohol having a CvC double bond in its skeleton. Pt black
was selected as an oxidation catalyst because it was known to
show good catalytic activity among various solid catalysts in
the batch processes.9a Because the contact time in the catalytic
column is around 2 minutes (min), there is an actual demand
for selection of a highly active catalyst to proceed with quick
oxidation. On the other hand, Pt has enough redox potential
to decompose H2O2. Therefore, the optimization of reaction
conditions such as the selection of catalysts, the concentration
of reactants and H2O2, and the tuning of the flow rate to tune
the contact time and contact order for Pt black, H2O2, and 1 is
required.
We screened the mixture of Pt black and metal oxides as
catalysts by using a flow reactor equipped with a glass column
reactor (length (L): 100 mm, inner diameter (ID): 5 mm)
packed with a catalyst, two pumps (one for delivering 1 and
the other for delivering aq. H2O2 to the column reactor), a con-
necting attachment, and flasks for solution storage, as shown
in Fig. 1. Eluent 1 was set to tert-amyl alcohol (t-amylOH)
because the reaction required a tertiary alcohol that would not
oxidize and have a high boiling point over 90 °C.
Optimization of the reaction conditions for the continuous
flow oxidation
Optimizing the contact time of the substrate with Pt and H2O2
is important to proceed with selective oxidation. The catalyst
column packed with 40 mg of Pt and 960 mg of SiO2 was pre-
pared, and the reaction conditions were optimized by adjust-
ing the reaction temperature, flow rate, and concentrations of
1 and H2O2 (Fig. 2 and Tables S1–S4†). The yield of 1 increased
upon raising the reaction temperature from 60 °C to 90 °C
(Fig. 2a). A reaction temperature over 90 °C is not appropriate
for the oxidation, as H2O2 decomposition tends to occur at
temperatures over 95 °C, and the boiling point of water is
100 °C, at which the generated steam would inhibit the flow of
1 and H2O2. We selected 0.4 mol L−1 as the optimal concen-
tration of 1 in t-amylOH solution to obtain 2 in 97% yield
(Fig. 2b). In the case of using 0.6 mol L−1 1/t-amylOH solution,
the conversion of 1 stopped at approximately 80% (Fig. 2b), as
the activity of the Pt catalyst was not sufficient to oxidize all
the amount of the supplied 1. However, the overreaction of 1
to form (E)-cinnamic acid (3) was observed at a 0.2 mol L−1
concentration of 1. The second stage oxidation of 2 to give 3 by
The Pt black catalyst has good chemoselectivity for the oxi-
dation of 1 in a batch process.9 However, the simple appli-
Fig. 1 H2O2 oxidation of 1 using a flow reactor.
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Fig. 3 Pt catalytic activity test. (a) Screening of the catalyst amounts at
the L = 100 mm column; (b) comparison of the column lengths (50 and
100 mm) using the same Pt + SiO2 catalyst. The base reaction conditions
are as follows: 0.4 mol L−1 1 in t-amylOH solution, 6 wt% aq. H2O2,
90 °C reaction temperature, and 0.3 ml min−1 flow rate. The conversion
and yield were the average of the results at 15, 30, and 60 min reaction
times, respectively.
(Fig. 3a). Notably, using 40 mg Pt black, the highest yield of 2
under the same reaction conditions was achieved (Fig. 3a). A
comparison of conversions of 1 and yields of 2 between the
reactions using a 10 cm column (using 40 mg of Pt and
960 mg of SiO2) and a 50 mm column (using 20 mg of Pt and
480 mg of SiO2) showed the remaining capacity of the Pt cata-
lytic activity (Fig. 3b). In the case of the 100 mm column, the
oxidation completed giving 2 in 97% yield, whereas the 50 mm
Pt column achieved approximately 60% conversion (Fig. 3b).
The amount of Pt black in the column reactor was related to
the yields of 2 because Pt did not give other by-products except
for 3. The reaction conditions might be freely designed to
obtain a reaction with a high-yield of over 90% by optimizing
the reaction temperature, concentrations of 1 and H2O2, flow
rate, and catalyst amounts.
Fig. 2 (a) Reaction temperature optimization. (b) Screening of the con-
centration of 1. (c) Screening of the concentrations of aq. H2O2. (d) Flow
rate optimization. The base reaction conditions are as follows: 40 mg of
Pt black, 960 mg of SiO2, 0.4 mol L−1 1 in t-amylOH solution, 6 wt% aq.
H2O2, 90 °C reaction temperature, and 0.3 ml min−1 flow rate. The con-
version and yield were the average of the results at 15, 30, and 60 min
reaction times, respectively.
the Pt catalyst began before the ejection of 2 from the column
reactor, although the second stage oxidation was difficult to
proceed for compounds with the CvC double bond, such as 2
(Fig. 2b). Delivering only water in the absence of H2O2 did not
give 2 at all. The oxidation reaction required H2O2 as a term-
inal oxidant. A higher concentration of H2O2 caused the for-
mation of 3 in 8% yield when we used 10% aq. H2O2 (Fig. 2c).
The concentration of 6% aq. H2O2 is sufficient for the oxi-
dation to proceed (Fig. 2c). A flow rate of 0.3 ml L−1 was the
best when we set the concentration of 1 to 0.4 mol L−1 and 6%
aq. H2O2 at 90 °C as reaction conditions, to give 2 in 97% yield
(Fig. 2d). The only side product was the corresponding acid 3
with a yield of 2% (Fig. 2d). These results showed the possi-
bility of tuning the reaction that could stop at the first stage
oxidation reaction from 1 to 2, resulting in the achievement of
the selective oxidation of 1 using a flow reactor under the opti-
mized conditions.
The continuous flow oxidation was performed for over 50 h
under the optimized conditions (Fig. 4 and Table S7†). A slight
Next, we checked the correlation between the catalyst
amounts and the yields of 2 in the flow oxidation (Fig. 3,
Tables S5 and S6†). When the reaction conditions were set as
0.4 mol L−1 1 in t-amylOH solution, 6 wt% aq. H2O2, 90 °C,
and a flow rate of 0.3 ml min−1 for 1 and H2O2, then 20 mg of
Pt black in the catalyst column was not sufficient to complete
the oxidation to give 2 in ca. 70% yield (Fig. 3a). However,
Fig. 4 Effect of the air trap on long-term H2O2 oxidation. The reaction
conditions are as follows: 40 mg of Pt black, 960 mg of SiO2, 0.4 mol
L
−1 1 in t-amylOH solution, 6 wt% aq. H2O2, 90 °C reaction temperature,
and 0.3 ml min−1 flow rate. Yields and conversions were determined by
60 mg of Pt resulted in overoxidation to give 3 in 6% yield GC analysis based on 1.
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Table 2 H2O2 oxidation of various alcohols using a flow reactora
decomposition of H2O2 in a storage flask occurred over 40 h,
and the O2 generated inhibited the pump delivery. Therefore, a
connection of an air-trap system immediately before the pump
in the H2O2 feeding route was useful for a long-term flow oxi-
dation. Without setting an air trap, the conversion dropped
every 24 h owing to the inhibition of H2O2 delivery by the O2
bubbles generated (Fig. 4, left). The reactivity was recovered
when we degassed the O2 bubbles from the route using a
syringe (Fig. 4, left). The inhibition of H2O2 delivery was coun-
tered using an air trap (Fig. 4, right).
After the connection of the air trap, the oxidation of 1 pro-
ceeded well to produce 2 in 95%–98% yields with excellent
selectivity for over 120 h (Fig. 5 and Table S8†). The optimized
reaction conditions are as follows: 40 mg of Pt black, 960 mg
of SiO2, 0.4 mol L−1 1 in t-amylOH solution, 6 wt% aq. H2O2,
90 °C reaction temperature, and 0.3 ml min−1 flow rate. The
only by-product was 3 in 1% yield.
Yield
(%)
Selectivity
(%)
Entry
1
Substrates
Products
96b
99c
98c
99c
2
3
92b
91b,d
4
5
6
83b
92b
95b
95c
93c
95c
Application to various alcohols in the Pt-catalyzed selective
oxidation using H2O2 as an oxidant
The developed flow reaction was applicable to various alco-
hols, including aliphatic, benzyl, and allylic alcohols (Table 2).
In addition to 2, other allylic alcohols were also successfully
oxidized to give their corresponding aldehydes, i.e., 4–8, in
83%–95% yields. 2-Methyl- and 3-methyl-substituted allylic
alcohols were also oxidized to give their corresponding alde-
hydes (4 and 8) in 92% and 95% yields, respectively. The
results suggested that steric hindrance due to the methyl
group did not affect the reactivity and that the substrates
approached the Pt surface from the direction in which the
CvC double bond was parallel to the Pt surface plane.
Substituted cinnamyl alcohol and linear allylic alcohols were
successfully oxidized to give their corresponding aldehydes (5,
6 and 7) in 91%, 83% and 92% yields, respectively. Benzyl
alcohol is easily converted to benzaldehyde (9) by the oxidation
7
91e
7e
93c
8
9
94e
55e
99c
99c
10
52e
31e
62c
a Reaction conditions: 40 mg of Pt black, 960 mg of SiO2, 0.4 mol L−1
alcohol in t-amylOH solution, 6 wt% aq. H2O2, 90 °C reaction tempera-
ture, 1 h, and 0.3 ml min−1 flow rate. b Isolated yield. c Selectivity =
yield/(100 − remaining alcohol yield) × 100 (%). d 0.1 mol L−1 alcohol
in t-amylOH solution. e Determined by GC analysis based on alcohol.
of H2O2 because of the easy contact between the Pt black and
substrate facilitated by the aromatic ring and its high electro-
philicity at the benzyl position. An electrophilic character of
para-substituted benzyl alcohols in the presence of a Pt black
catalyst was reported from the Hammett plot.9b The overoxida-
tion of 9 also occurred to form its corresponding carboxylic
acid (10) in 7% yield. Substituted benzyl alcohols also reacted
with H2O2 to give their corresponding aldehydes (11 and 12) in
94% and 55% yields, respectively. Aliphatic alcohols, including
simple chain-shaped primary alcohols, were also easily oxi-
dized to give their corresponding aldehydes and carboxylic
acids. For example, 1-octanol oxidized to give its corres-
Fig. 5 Oxidation of 1 to 2 for over 120 h.
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ponding aldehyde (13) and carboxylic acid (14) in 52% and 31%
yields, respectively. Nevertheless, under the reaction conditions
developed, it was still difficult to inhibit the overoxidation of
13.13 However, no products other than 13 and 14 were produced.
Reaction mechanism of H2O2 flow oxidation
From the ICP-AES analysis, Pt black was not detected at all
from the solution after the oxidation of 1. Additionally, the
pore size of the filter connected to the column reactor was
2 µm, suggesting that the reaction proceeded on the surface of
Pt black, as the size of Pt particles exceeded 2 µm. The reaction
mechanism was estimated considering the reactivities of
various alcohols and XPS data, in addition to following the
previous work on Pt black-catalyzed oxidation in a batch
process.9 The oxidation of 1 in the presence of 1-octene
decreased the yield of 2 from 95% to 65%, thereby confirming
the importance of the coordination of 1 toward a Pt active site
because the coordination of 1-octene to Pt inhibited the pro-
gress of the reaction (Scheme 1 and Table S9†).
We developed the reaction by setting the concentration of
aq. H2O2 to as low as 6% (Fig. 2c), which could result in the oxi-
dation of 1 before the decomposition of H2O2 under the opti-
mized reaction conditions because the reaction did not proceed
in the absence of H2O2. Considering the results in Fig. 2,
Table 2, and Scheme 1 and previous reports, the reaction
mechanism was estimated as shown in Scheme 2. Pt black
would be covered almost completely by a solvent and substrates,
thereby preventing the extra H2O2 decomposition due to the
contact between Pt black and H2O2. Afterward, H2O2 addition
resulted in the formation of an aldehyde, followed by the
coordination of the new alcohol to the Pt surface, which facili-
tated the desorption of the aldehyde from the Pt surface.
Fig. 6 XPS spectra of Pt black before and after the reaction.
The preservation of Pt(0) during the reaction is the key to
the developed flow oxidation. Pt(0) enables the coordination of
CvC double bonds, and this coordination prevents the
contact of H2O2 with the Pt surface to cause the catalytic H2O2
decomposition. The surface oxidation state of Pt black in the
Pt + SiO2 column reactor was examined by XPS before and
after the reaction (Fig. 6). By referencing to C 1s (284.3 eV), the
peaks at 70.7 and 74.2 eV BEs were ascribed to Pt 4f7/2 and Pt
4f5/2, respectively. These values of the Pt 4f peaks were close to
70.9 and 74.2 eV, which were assigned to the BEs of the bulk
Pt metal, and the observed peaks corresponded to Pt(0).14
After the reaction, there was no change in the peaks assigned
at Pt 4f7/2 and Pt 4f5/2, demonstrating the preservation of Pt(0)
during the reaction. Additionally, PtO2, which is a good precur-
sor of platinum black,15 did not exhibit the reactivity for the
oxidation.9 The preservation of Pt(0) was thus critical to achiev-
ing the high-yield syntheses of aldehydes.
Concerning the quantification of the strength of the Pt-
oxide–support interaction, Nagai et al. suggested that SiO2
showed the lowest interaction with Pt in Pt-supported SiO2,
among various metal oxides, including Al2O3, ZrO2, TiO2, and
CeO2, which are frequently used as support oxides.11
Moreover, Pt-supported Al2O3 showed a similar Pt–support
interaction strength to that of Pt-supported SiO2 and thus had
the second-lowest BE of the O (1s) electron after Pt-supported
SiO2.11 The slightly less reactivity of Pt + Al2O3 than that of Pt +
SiO2 is in good accordance with the order of the Pt–support
interaction strength (Table 1). SiO2 seems to retain Pt(0)
during the reaction. The low interaction between Pt and SiO2
facilitates the access of the CvC double bonds in allylic alco-
hols toward the Pt(0) surface in the Pt + SiO2 catalyst, as Pt can
freely coordinate with substrates without binding with SiO2.
Scheme 1 H2O2 flow oxidation of 1 in the presence of 1-octene. The
reaction conditions are as follows: 40 mg of Pt black, 960 mg of SiO2, a
mixture of each 0.4 mol L−1 1 and 0.4 mol L−1 1-octene in t-amylOH
solution, 6 wt% aq. H2O2, 90 °C reaction temperature, and 0.3 ml min−1
flow rate. Yields and conversions were determined by GC analysis based
on 1.
Conclusions
A fixed-bed flow reactor equipped with the Pt + SiO2 catalyst
for the selective synthesis of α,β-unsaturated aldehydes was
developed. During the oxidation reaction, the contact time of
Scheme 2 Estimated reaction mechanism of H2O2 flow oxidation.
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the substrate with H2O2 and Pt was controlled, inhibiting the obtained in 2% yield. The H NMR spectroscopic data of the
decomposition of H2O2 to utilize selective oxidation. A mixture product were in accordance with the reported NMR data.16
of Pt black and SiO2 enabled the preservation of Pt(0) during
Other aldehydes 4–9 and 11–13 were also synthesized, and
the catalytic reaction because of the weak interaction between carboxylic acids 10 and 14 were produced by the same
Pt and SiO2. The oxidation of 1 proceeded selectively to obtain methodology.16
2 in over 95% yield for 120 h continuously because of the pres-
ervation of the Pt(0) species on the Pt black surface in the Pt +
Materials and methods
SiO2 catalyst column under the optimized reaction conditions.
Pt black was obtained from N.E. CHEMCAT Co. Aluminum
The developed continuous flow reaction can be used to
oxide (Al2O3) was obtained from Nikki Universal Co., Ltd
oxidize various alcohols, including allylic, benzylic, and ali-
(JCS-ALO-6, a reference catalyst in the Catalysis Society of
phatic alcohols, to their corresponding aldehydes. It may be
Japan (CSJ)). Cerium oxide (CeO2) was obtained from Daiichi
directly utilized for the next reactions, such as amide synthesis
Kigenso Kagaku Kogyo Co., Ltd. Titanium oxide (TiO2) was
obtained from Merck Co., Ltd. (E)-Cinnamyl alcohol, 2-methyl-
3-phenyl-2-propen-1-ol, geraniol, (E)-2-octen-1-ol, n-dodecane,
tert-amyl alcohol, 1-octanol, 1-octene, (E)-4-nitrocinnamyl
and esterification, as tandem reactions because the co-product
derived from H2O2 is only water.
alcohol, (E)-2-nonen-1-ol, 4-methoxybenzyl alcohol, 4-bromo-
benzyl alcohol and benzyl alcohol were obtained from the
Experimental
Tokyo Chemical Industry Co., Ltd. Silica (SiO2, Wakogel
C-200), magnesium oxide (MgO), acetonitrile, ethyl acetate,
n-hexane, and CDCl3 (containing 0.05 wt% of tetramethyl-
silane (TMS)) were obtained from FUJIFILM Wako Pure
Chemical Industries, Ltd. 35 wt% hydrogen peroxide was
obtained from Kanto Chemical Co., Inc.
As examples, we herein report some optimized methods. The
reaction conditions have been screened by following the pro-
cedures reported in the table captions.
H2O2 oxidation of (E)-cinnamyl alcohol (1) by using a continu-
ous flow reactor for over 120 h reaction time (as standard reac-
tion conditions)
Sample analysis
SiO2 (960 mg) and Pt black (40 mg) were mixed and packed in
a column reactor (L = 100 mm and ID = 5 mm) equipped with
double plunger pumps. The first plunger pump was used for
passing 1 in t-amylOH solution (0.40 M) and the other for
passing 6% H2O2 aqueous solution. The two lines were com-
bined just before the column reactor by using a connector.
Before the reaction began, t-amylOH was passed at 25 °C for
10 min to prepare the flow reactor conditions. The reaction
was initiated at a 0.3 mL min−1 flow rate for each plunger
pump under almost atmospheric pressure (0.4 MPa). The resi-
dence time was estimated to be 2.25 min at the column
reactor. The column was heated at 90 °C, and the 6 ml reaction
solution was corrected every hour to check the product yields
by using GC. The sample used for GC was prepared as follows:
extraction of the organic phase from the collected sample, fol-
lowed by dilution using acetonitrile. An air trap was utilized to
maintain steady delivery of aq. H2O2 to the column reactor.
GC analyses were performed using a Shimadzu GC-2014 gas
chromatograph system equipped with an Inert Cap 1 column
(0.25 mm × 30 m, GL Sciences Inc.). The H NMR (400 MHz)
1
spectra were recorded using a JEOL ECX-400P spectrometer at
25 °C. Chemical shifts (δ) were measured in parts per million
relative to TMS at 0.00 ppm for 1H, unless otherwise noted.
XPS spectra were recorded using a VG ESCALab 250 spectro-
meter fitted with an Al Kα X-ray source (1486.6 eV). The
elemental analysis of Pt after the reaction was performed
using a Shimadzu ICPE-9000 inductively coupled plasma-
atomic emission spectrometer (ICP-AES). The BE was based on
C 1s (284.3 eV).
Flow reactors
As the apparatus of the flow synthesis system, an LC plunger
pump (FLOM, Inc., Intelligent pump UI22-110S for substrates
and UI22-110P for aq. H2O2), a column reactor oven (TOKYO
RIKAKIKAI CO., LTD, Column Flow Reactor MCR-1000 and
XCR-1000), and a fraction collector (Advantec Toyo Kaisha,
Ltd, fraction collector CHF122SC) were used. An air trap
(Nihon Seimitsu Kagaku Co. Ltd, AD-2) was used for delivering
degassed aq. H2O2. An empty column (SUS316, L = 100 mm,
ID = 5 mm, and filter pore size = 2 µm) was purchased from
TOMOE WORKS CO., LTD.
Synthesis of (E)-cinnamaldehyde (2) using a continuous flow
reactor (isolation experiment under standard reaction
conditions)
The flow oxidation reaction was performed under the same
conditions as those stated in the previous section. The column
reactor was finally rinsed by passing t-amylOH (20 mL), and all
the solutions that were passed through the catalyst column
were collected. After separating the organic phase from the
water phase, the product was purified by column chromato-
graphy by eluting with n-hexane : ethyl acetate (10 : 1 (v/v)). The
product (E)-cinnamaldehyde (2) was obtained after the
removal of the eluents as a colorless oil (0.92 g, 96% yield). As
Conflicts of interest
confirmed by GC analysis, (E)-cinnamic acid (3) was also There are no conflicts to declare.
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Paper
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Acknowledgements
This article is based on results obtained from a project,
JPNP19004, subsidized by the New Energy and Industrial
Technology Development Organization (NEDO), Japan.
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