Visible light catalyzed anti-markovnikov hydration of styrene to 2-phenylethanol: From batch to continuous

Article abstract of DOI:10.1016/j.jphotochem.2019.112340

The 2-phenylethanol production by traditional chemical methods requires multi-step reactions, in which harsh conditions such as high temperature or strong acid/base are required and undesired by-products are easily produced. The visible light catalyzed anti-Markovnikov hydration of styrene is a single-step reaction using non-toxic catalyst under mild conditions. However, this reaction usually takes ten or even dozens of hours, facing the problem in scale up. The present work aims to intensify this reaction in continuous flow microreactor with comparison to traditional batch reactor. The effects of light source shape, reaction temperature, substrate concentration and catalyst concentration on the reaction were investigated. The continuous flow microreactor permitted to ensure more uniform light intensity and larger specific surface area, the reaction rate could thus be enhanced. The maximum productivity of 2-phenylethanol was 0.122 mol/(L.h), which was 2.5 times higher than that obtained in test tube under the same reaction conditions and 34 times higher than that reported in previous literature. The optimal photosensitizer concentration was 2 %. The increase of substrate concentration would lead to the addition reaction between styrene cationic intermediates with styrene, thereby decreasing the selectivity of 2-phenylethanol.

Full text of DOI:10.1016/j.jphotochem.2019.112340

Journal Pre-proof
Visible light catalyzed Anti-Markovnikov hydration of styrene to
2-phenylethanol: from batch to continuous
Yuhang Chen (Methodology) (Investigation) (Writing - original draft),
Jie Zhang (Writing - review and editing), Zhiyong Tang
(Conceptualization) (Supervision) (Funding acquisition), Yuhan Sun
(Supervision)
PII:
S1010-6030(19)31542-4
DOI:
https://doi.org/10.1016/j.jphotochem.2019.112340
JPC 112340
Reference:
To appear in:
Journal of Photochemistry & Photobiology, A: Chemistry
Received Date:
Revised Date:
Accepted Date:
6 September 2019
5 December 2019
22 December 2019
Please cite this article as: Chen Y, Zhang J, Tang Z, Sun Y, Visible light catalyzed
Anti-Markovnikov hydration of styrene to 2-phenylethanol: from batch to continuous, Journal
of Photochemistry and amp; Photobiology, A: Chemistry (2020),
doi: https://doi.org/10.1016/j.jphotochem.2019.112340
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Visible light catalyzed Anti-Markovnikov hydration of
styrene to 2-phenylethanol: from batch to continuous
Yuhang Chena,b, Jie Zhanga,b,*, Zhiyong Tanga,b,c,*,Yuhan Suna,b,c
aCAS Key Laboratory of Low-Carbon Conversion Science and Engineering, Shanghai
Advanced Research Institute, Chinese Academy of Sciences, Shanghai, 201203, PR China
bSchool of Chemical Engineering, University of Chinese Academy of Sciences, Beijing, 100049,
PR China
cSchool of Physical Science and Technology, Shanghai Tech University, Shanghai, 201210, PR
China
*Corresponding authors
Email address: zhangjie@sari.ac.cn (J. Zhang); tangzy@sari.ac.cn (Z. Tang)
1

Graphical abstract
Highlights:
 2-phenylethanol by anti-Markovnikov hydration of styrene was synthetized for
the first time in a continuous flow microreactor
 The microreactor performance was compared to a traditional batch reactor
 The effects of various reaction parameters were examined offering insight into
reaction mechanism
 The microreactor outperformed the batch reactor in shorter reaction time and
higher productivity of 2-phenylethanol
2

Abstract：
The 2-phenylethanol production by traditional chemical methods requires multi-
step reactions, in which harsh conditions such as high temperature or strong acid/base
are required and undesired by-products are easily produced. The visible light catalyzed
anti-Markovnikov hydration of styrene is a single-step reaction using non-toxic catalyst
under mild conditions. However, this reaction usually takes ten or even dozens of hours,
facing the problem in scale up. The present work aims to intensify this reaction in
continuous flow microreactor with comparison to traditional batch reactor. The effects
of light source shape, reaction temperature, substrate concentration and catalyst
concentration on the reaction were investigated. The continuous flow microreactor
permitted to ensure more uniform light intensity and larger specific surface area, the
reaction rate could thus be enhanced. The maximum productivity of 2-phenylethanol
was 0.122 mol/(L.h), which was 2.5 times higher than that obtained in test tube under
the same reaction conditions and 34 times higher than that reported in previous
literature. The optimal photosensitizer concentration was 2%. The increase of substrate
concentration would lead to the addition reaction between styrene cationic
intermediates with styrene, thereby decreasing the selectivity of 2-phenylethanol.
keywords：photocatalytic; continuous flow microreactor; anti-Markovnikov; 2-
phenylethanol; process intensification;
3

1. Introduction
As an aromatic alcohol with a mild rose fragrance, 2-phenylethanol (commonly
known as phenethyl alcohol) is a key molecule used in the fragrance and food industries
[1, 2]. It is also an important raw material for the synthesis of other flavourings and
pharmaceutical compounds, like phenylacetaldehyde and phenylethyl acetate [3].
Natural 2-phenylethanol is mainly extracted from the essential oil of roses, jasmine and
other flowers, in which the content of 2-phenylethanol accounts for about 60% [4].
However, the natural plant grows slowly and its essential oil content is very low
yielding very limited 2-phenylethanol. As a result, it is very difficult to meet its huge
market demand with this approach from nature. In recent years, biotechnological
approach has gained increasing attention as an alternative process [5-7]. This method
uses microbial fermentation to produce 2-phenylethanol from phenylalanine. However,
due to the antibacterial characteristics of 2-phenylethanol, its final concentration is
limited to a low level. Moreover, the fermentation cycle usually lasts for several days,
making scale-up difficult.
Since long ago, chemists have been exploring the chemical synthesis of 2-
phenylethanol, which can be divided into three routes depending on the raw material
and catalyst [8-11], as summarized in Scheme 1. The benzene-ethylene oxide method
(Scheme 1.1a) is a typical Friedel-craft reaction. In the presence of anhydrous
aluminum trichloride, benzene reacts with ethylene oxide to form 2-phenylethylalcohol
salt, which is further hydrolyzed to 2-phenylethanol. This process is simple with low
equipment requirements, representing thus current main chemical method to produce
2-phenylethanol. Nevertheless, the produced 2-phenylethanol is accompanied by many
impurities with unpleasant odor, such as biphenyl, 2-ethylbenzene chloride,
chloroethanol. The boiling point of these byproducts is close to the desired 2-
phenylethanol, causing difficult separation. In the toluene method (Scheme 1.1b),
toluene is firstly chlorinated to benzylchloride by side chain chlorination, and then
cyanolyzed to benzylnitrile, followed by reduction to phenylethylamine, which finally
converted to 2-phenylethanol. This process is very complex and involves highly toxic
potassium cyanide, restricting its application in large-scale. In the styrene method
(Scheme 1.1c), 2-phenylethanol is obtained by catalytic hydrogenation of phenyl
4

ethylene oxide, which is produced from styrene. The hydroboration/oxidation of
styrene is a widely used approach for preparing alcohols with anti-Markovnikov
regioselectivity (Scheme 1.1d). However, this process requires a stoichiometric amount
of borane reagents and peroxides, causing chemical waste problems. Therefore, it is
noticeable that all the above four traditional chemical methods involve multi-steps, and
face problems of harsh reaction conditions and/or producing annoying byproducts.
Scheme 1. Synthesis route of 2-phenylethanol
Recently, the direct anti-Markovnikov hydration of styrene for producing 2-
phenylethanol has attracted considerable attention. This kind of technology could be
considered to be an attractive alternative approach because of its economy in atom
utilization. However, it should be mentioned that achieving anti-Markovnikov
hydration of alkenes under mild conditions has been a dream of chemists for a long
time, and it has been referred as one of top ten challenges of catalysis [12]. Grubbs and
5

co-workers [13] proposed a general palladium catalyst system for 2-phenylethanol from
styrene through the direct anti-Markovnikov hydration reaction (Scheme 1.2a).
Recently, palladium catalyst was also used by M. Tokunaga group [14] for converting
olefins to corresponding primary alcohols in presence of water and oxygen.
Nevertheless, these approaches are not very economical from a commercial application
perspective, as high concentrations of expensive noble metals were required as catalyst.
Consequently, it is worthwhile to develop a less-hazardous, cost-effective, and
noblemetal-free catalytic system for the direct anti-Markovnikov hydration of styrene.
In recent ten years, organic synthesis catalyzed by visible light has been an
emergent area of research and scientific interest due to its mild reaction conditions and
high product selectivity [15-17]. Nicewicz and co-workers [18-21] proposed 9-Mesityl-
10-methylacridinium perchlorate as photocatalyst for the anti-Markovnikov hydro-
functionalization of alkenes. Based on their work, Hu et al. [11] combined 9-mesityl-
10-methylacridinium perchlorate and phenyl disulfide as photoredox/hydrogen atom
transfer dual catalytic system to realize visible-light-mediated anti-Markovnikov
hydration of styrene, as shown in Scheme 1.3a. Although using phenyl disulfide as
catalysis produces the thiophenol, the formed thiophenol converts finally to phenyl
disulfide to complete catalysis cycle. This is different from indirect synthesis route,
which forms unpleasant odor by-product. Hence, visible light catalyzed Anti-
Markovnikov hydration of styrene is still an attractive alternative approach to produce
2-phenylethanol. Nevertheless, the light transfer was restricted by the Beer-Lambert
law. Due to the strong molar extinction coefficient of photosensitizers, the light emitted
by the light source was difficult to penetrate the reaction mixture, which suggests that
the visible-light photoredox reaction might only take place in the proximal area of the
vessel wall [22-24], leading to tens of hours in reaction time.
The microreactor diameter is <1.0 mm and thus the optical trajectory is small. The
large specific surface area of microreactors allows receiving more photons by the
reaction solution, leading to the increasing reaction rate [25]. Consequently, in the past
few years, micro-flow reactors have demonstrated significant promise in the area of
organic photochemistry [26-32]. Hessel et al.[29] realized photocatalyzed
6

trifluoromethylation of phenylthiophenol using winding perfluoroalkoxy (PFA) tubing
as microreactor. Due to the high efficiency of gas-liquid mass transfer, the microreactor
took only a few minutes for the complete transformation of reactant, while the test tube
needed up to an hour. Hamami et al. [33] also took advantage of PFA tubing as
continuous flow photocatalytic reactor to enhance the photocatalytic oxidation of
citronella alcohol using LED as light source. The effects of photocatalyst concentration,
oxygen partial pressure and PFA tube diameter on the reaction were investigated to
obtain the optimum operating conditions. Moreover, due to the small volume of the
microreactor, the safety of the reaction could be greatly improved. The photocatalytic
carboxylation of styrene was studied in a similar continuous flow microreactor [34],
which reduced the reaction time from 1 hour for batch to 8 min with improved
reproducibility.
In the present work, the visible light catalyzed anti-Markovnikov hydration of
styrene to 2-phenylethanol was realized for the first time in continuous flow, with the
purpose to shorten the reaction time and reduce the required catalyst amount. The
performance of microreactor was compared to conventional batch reactor. The effects
of light source, reaction temperature, substrate concentration and catalyst concentration
on the reaction were examined experimentally so as to optimize the reaction conditions
and better understand the reaction mechanism.
2. Experimental
2.1. Experimental setup
As shown in Fig. 1, in this study, a PFA tube (IDEX Health and Science) loop
around a test tube was used as a microreactor to carry out the continuous flow
photocatalyzed anti-Markovnikov hydration of styrene reaction. The internal diameter
of the PFA tube was 1.0 mm and the external diameter was 2.0 mm. The total reaction
length was 5.1 m leading to a total reaction volume of 4.0 mL. PFAtube is characterized
of chemical compatibility, thermal stability, and high transparency, so it is frequently
7

applied to as microreactors for photochemical reaction. In the present work, the
transmittance of PFA film with 0.45 mm thickness was measured as 91.6% at 450 nm.
The real transmittance of the present PFA tube, which represented a thickness of 0.5
mm, was estimated as 85-90% at 450 nm (see details in Supplementary Material). In
the meantime, a test tube was used as conventional batch reactor for comparison.
Fig. 1. PFA capillary microreactor
The experimental set-up is illustrated in Fig. 2 (details see the Supplementary
Material). To obtain a controlled reaction temperature, the whole microreactor was
immersed in a water bath, which was illuminated by blue LED light (Planck, Shenzhen,

max=450 nm, 80W/m2). The reactant, catalyst and solvent were firstly mixed prior to
be injected into the tubing via a syringe pump (Longer Pump LSP01-3A), which allows
a flowrate ranging from 0.001 μl/min to 43.349 ml/min. In the present study, the
delivery rate of reaction mixture was varied from 0.67 mL/h to 8.0 mL/h to adjust the
residence time. In parallel, the conventional tube reactions were carried out using the
same light source and water bath. It is worthwhile mentioning that two light source
shape (planar and annular LED) were used in test tube for evaluating its effect on
photocatalytic reaction. Fig. 3 displays the photos of two working reactors.
Fig. 2. Schematic diagram of continuous flow microreactor platform
8

Fig. 3. Different photoreactors and light sources. (a) and test tube (b) annular
LED and test tube (c) annular LED and microreactor
2.2. Method and materials
Prior to every photocatalytic reaction, a mixture solution of reaction substrate and
catalyst was prepared in a test tube as follows. Unless otherwise stated, analytical grade
solvents and commercially available reagents were used without further purification.
The substrate, 0.156 g styrene (J&K, with purity of 98%), and the photocatalysts,
0.0158 g 9-Mesityl-10-methylacridinium perchlorate (J&K, with purity of 98%), 0.068
g phenyl disulfide (Aladdin, with purity of 99%), were weighted and then dissolved in
a mixture of 10.0 mL acetonitrile (Aladdin，purity >99.5) and 1.0 mL deionized water
in a test tube (20 mL) equipped with a stir bar. The test tube was then sealed with
silicone stoppers and was stirred in magnetic stirrer for 5 minutes. Afterwards, argon
was pumped into the test tube for 5 minutes in order to remove completely the inside
air. It should be noted that the amount of chemical reagents indicated in above process
corresponded to the standard reaction conditions in this study: 0.15 M styrene, 3 mol%
9-Mesityl-10-methylacridinium perchlorate, and 20 mol% phenyl disulfide.
The reaction solution prepared as above was extracted by a syringe under argon
atmosphere and then mounted on a syringe pump. The microreactor was subsequently
put into a water bath and the inside air was excluded completely. After the temperature
of water bath stabilized, the reactant solution was pumped into the microreactor with
9

regulated flowrate according to the desired residence time. The anti-Markovnikov
hydration reaction was conducted with the irradiation of blue LED, and the products
were continuously collected in a test tube for further analysis.
As mentioned previously, experiments were also carried out in conventional batch
reactor. For that, a test tube with prepared solution was placed directly in a water bath
with the irradiation of blue LED. After the reaction time was reached, the LED light
was turned off and the products were sent to be analyzed.
2.3. Analysis method
The reaction products were characterized by GC-MS (Agilent 7890A-5975C) and
quantitatively analyzed by GC (GC-2014 Shimadzu) equipped with an SH-Rtx-Wax
column using nitrogen as a carrier gas. The GC was calibrated in advance with internal
standard curve method using biphenyl (Aladdin, purity>99.5%). The GC injection
volume was 1.0 L with a split ratio of 50. The initial column temperature was 50℃,
and then increased to 220℃ with a heating rate of 10℃/min. The retention time was 23
min.
3. Results and discussion
3.1. The effect of light source shape
In this study, the effect of light source shape on the photocatalytic reaction was
firstly investigated. Fig. 4 illustrates the evaluation of 2-phenylethanol yield and styrene
conversion as function of reaction time. The net turnover frequency (TOF) of catalyst
is summarized in Table 1. It can be seen that the application of annular LED greatly
reduced the reaction time required for the test tube. With planar LED array, the
conversion of styrene reached 87% in test tube after 16 hours of irradiation and the
totally conversion of styrene took more than 20 hours. The corresponding TOF was 1.8
h-1. Replacing the planar LED array by annular LED resulted in 96% of styrene
conversion with a TOF of 8 h-1 after 4 hours of irradiation. This could be explained by
10

the increased light intensity of the annular LED, which increased the amount of
radiation received by the photosensitizer in the test tube per unit of time, leading to an
increase in the reaction rate [22].
Fig. 4. Styrene conversion (a) and yield of 2-phenylethanol (b) in different light
sources and reactors (Experimental conditions: 25℃, 0.15M Styrene, 3mol%
-
photocatalyst Acr+-Mes ClO4 , 20mol% HAT catalyst Ph-S-S-Ph)
Table 1. Conversion and TOF in different light sources and reactors
Reaction system
time styrene Conversion TOF[a] AQY[b]
[h] [mmol]
[%]
87
[h-1]
1.8
8
[%]
2.03
6.34
1.72
planar LED array + test tube
annular LED + test tube
16
4
0.3
0.3
0.6
96
annular LED +microreactor
2
87
14.5
n(styrene)×conversion
[a] net turnover frequency (TOF)=
−
n(Acr −Mes ClO )×time
+
4
[b] apparent quantum yield (AQY) (see Supplementary Material for detail calculation)
After screening out more efficient light source shape, we then investigated the
photocatalytic reaction in microreactor with annular LED light. As can be seen from
Fig. 4b, in the first 4 hours, the production rate of 2-phenylethanol in the microreactor
was higher than that in the test tube. Table 2 shows that the conversion of styrene in the
microreactor reached 87% after 2 hours irradiation, corresponding to a TOF of 14.5 h-
1, which was 81.3% higher than that in the test tube of 4 hours irradiation. Similar results
11

have been reported in the previous studies [23, 35].
Thanks to the larger specific surface area of the microreactor, a large part of the
reaction medium was kept very close to the light source, resulting in more received
energy in the microreactor as compared to that in the test tube [36]. The received optical
power by reagent was found as 160 W/L in the microreactor, while it was only 14 W/L
and 28 W/L in the test tube depending on the light source. Therefore, the increased
reaction rate observed in microreactor could be attributed to higher illumination.
Nevertheless, it was shown in Table 1 that the apparent quantum yield (AQY) of
microreactor was 1.72 %, which was lower than that in the test tube. As matter of fact,
the large specific surface area increases the received optical power of reaction medium
in the microreactor, while its overall volumetric flow rate is low due to the small
volumes. Therefore, the low throughput of the microreactor resulted in waste of lighting
power of LED, thus decreasing the AQY.
As shown in Fig. 4b, it was noticed that the yield of 2-phenylethanol in
microreactor decreased slightly from 61.9 % to 60 % when the reaction time
increased from 4 hours to 6 hours, whereas the yield of 2-phenylethanol reached 71%
in test tube with 6-8 hours of reaction time. This phenomenon was probably due to
the enhanced addition reaction between the styrene cation intermediates with styrene
in the microreactor with long reaction time, resulting in a decrease in the yield of 2-
phenylethanol.
3.2. The effect of temperature
Using annular LED lamp as the light source, we studied the photocatalytic reaction
under different reaction temperatures ranging from 25℃ to 70℃. As illustrated in Fig.
5, for the both test tube and microreactor, the yield of 2-phenylethanol was generally
favored by the increasing reaction temperature. But this promoting effect was less
pronounced with longer reaction time, and too high temperature might even inhibit the
2-phenylethanol production. In test tube (Fig. 5a), the yield of 2-phenylethanol
stabilized around 71% with a reaction temperature of 25℃ at 6-8 hours, while it
12

stabilized around 67.5% with a reaction temperature of 70℃ at 2-4 hours. The best 2-
phenylethanol yield was obtained at 75% with a reaction temperature of 40℃at 4 hours.
As seen in Fig. 5b, the curves of microreactor followed very similar trends as observed
in test tube. The curves seemed to reach flat at shorter time than test tube, which was 4
hours and 1 hour with a reaction temperature of 25℃and 70℃, respectively.
Fig. 5. Yield of 2-phenylethanol under different reaction temperatures (a) test tube (b)
microreactor (Experimental conditions: 0.15M Styrene, 3mol% photocatalyst Acr+-
-
Mes ClO4 , 20mol% HAT catalyst Ph-S-S-Ph)
Fig. 6. The yield of 2-phenylethanol as function of reaction temperature in the test
tube and microreactor (Experimental conditions: 0.15M Styrene, 3mol% photocatalyst
-
Acr+-Mes ClO4 , 20mol% HAT catalyst Ph-S-S-Ph, reaction time 1h)
13

Fig. 7. Schematic diagram of mass transfer between light limited zone and light
irradiance zone in different reaction systems
Fig. 6 exhibits the evaluation of yield to 2-phenylethanol as function of the
reaction temperature with 1 hour for the both test tube and microreactor. It can be seen
that the yield of 2-phenylethanol per unit time in both reactors was considerably favored
by the increasing of reaction temperature. In the present work, the molar extinction
coefficient for 9-Mesityl-10-methylacridinium perchlorate is 1887 M-1cm-1 and the light
transmission is limited Beer-Lambert law. After absorption partially by reactor wall,
the entered light intensity continues decreasing along the reactor cross-section. It was
calculated that under current reaction conditions, the entered light intensity was reduced
to 14% after 1 mm of reaction mixture (see Supplementary Material for details).
Therefore, as shown in Fig. 7, the light source failed to irradiate the entire volume of
the reactant solution, leading to a “light-starved” status. Mass transfer exists between
the light limited and light irradiance zone. Under higher temperatures, the accelerated
thermal motion of molecules enhanced the radial mixing, leading to the increase of
reaction rate, as observed in this work. Similar results have also been reported in the
literature [24]. However, it should be noted that too high reaction temperature might
cause problem of heat dissipation of the light source. Additionally, the working lifetime
of LED lamp will be shortened, and its output wavelength and power will become
instable after longtime operation under high temperature [37]. Hence, a reaction
temperature of 60℃was chosen for the following study. Meanwhile, it is also indicated
14

by the Fig. 6 that the microreactor could nearly double the yield of 2-phenylethanol at
every investigated reaction temperature, which was mainly due to its higher light
utilization efficiency.
3.3. The effect of substrate concentration
The effect of substrate concentration on the reaction was studied under the
irradiation of the annular LED lamp. It can also be seen from Fig. 8a&b that, with a
same reaction time, a decrease of 2-phenylethanol yield was resulted from the
increasing substrate concentration for the both reactors. The yield to 2-phenylethanol
was nearly reduced by half when the styrene concentration increased from 0.15 M to
0.6 M. With the increasing substrate concentration, the concentration of activated
styrene cationic intermediates in the reaction solution was increased, which would
intensify its addition reaction with the styrene. Therefore, the selectivity to 2-
phenylethanol decreased, as observed in Fig. 8a&b. It was worthwhile mentioning that
the peak of 1-phenyl-1,2,3,4-tetrahydronaphthalene was detected on GC-MS in the
present work, and its peak area increased with the increasing styrene concentration,
further proving our assumption.
When the styrene concentration increased from 0.15 M to 0.6 M, the photocatalyst
was increased too so as to maintain 3 mol%. As shown in Fig. 8c, with the increasing
photocatalyst concentration, the light penetrate distance decreased sharply. Therefore,
the “light-limited” regime increased in the test tube, leading to the increased proportion
of unexposed substrate. As a result, the required reaction time in the test tube was
prolonged from 3 hours to ≥ 10 hours. However, due to much smaller cross-section
and higher light illumination area, the reaction time required in the microreactor was
nearly not affected by the increasing substrate concentration, which remained fairly
constant at 2 hours.
15

Fig. 8. Yield of 2-phenylethanol with different substrate concentrations (a) test tube,
(b) microreactor (Experimental conditions: 60℃, 3mol% photocatalyst Acr+-Mes
-
ClO4 , 20mol% HAT catalyst Ph-S-S-Ph) (c) Plots of light transmittance versus the
-
distance of light propagation with three different concentrations Acr+-Mes ClO4
The increase of substrate concentration could increase the product concentration,
but this positive effect was offset by the decreasing selectivity to some extent. Hence,
it is necessary to strike a balance for an optimal productivity of 2-phenylethanol. As
seen in Fig. 9, for the both reactors, the productivity of 2-phenylethanol increased firstly,
and then dropped with the increasing reaction time with each substrate concentration.
The maximum productivity of 2-phenylethanol was 0.049 mol/(L.h) in the test tube
(0.3M styrene, 3 hours). The microreactor permitted to achieve a productivity of 0.122
mol/(L.h) (0.3M styrene, 1 hour), which was 2.5-fold of the test tube, and 34 times
higher than the reported value (0.0036 mol/(L.h)) in the literature [11].
16

Fig. 9. Productivity of 2-phenylethanol with different substrate concentrations (a)
test tube, (b) microreactor (Experimental conditions: 60℃, 3mol% photocatalyst
-
Acr+-Mes ClO4 , 20mol% HAT catalyst Ph-S-S-Ph)
3.4. The effect of catalyst concentration
The catalyst concentration is another important parameter which has a significant
influence on the photocatalytic reaction. In this work, we have studied the effect of
-
photocatalyst Acr+-Mes ClO4 concentration and HAT catalyst Ph-S-S-Ph concentration
in the test tube and microreactor using annular LED lamp as light source. It is noted
that the reaction time in the test tube was 2 hours, which was reduced to 1 hour in the
microreactor since similar styrene conversion and 2-phenylethanol yield could be
achieved.
-
Fig. 10. The effect of Acr+-Mes ClO4 concentration on the reaction. Reaction
time (a) test tube 2 hours (b) microreactor 1 hour (other experimental conditions:
60℃, 0.15M Styrene, 20mol% HAT catalyst Ph-S-S-Ph)
17

-
Fig. 10 displays the effect of Acr+-Mes ClO4 concentration on the styrene
conversion and 2-phenylethanol yield for the test tube (a) as well as the microreactor
(b). It can be observed that an optimal photosensitizer content 2 mol% existed in the
both reactors. When the photosensitizer content was lower than 2 mol%, the reaction
rate increased with the increasing photosensitizer content, which was in line with the
traditional reaction kinetics behavior. However, by the increasing the photosensitizer
content further (>2 mol%), the reaction rate was somehow inhibited by high
photosensitizer concentration. Indeed, the light transmission was limited by the beer-
lambert law. Although the photosensitizer concentration was high, not all presented
photosensitizer in the reactant solution were activated by the light, resulting in a
decrease of overall excited photosensitizers. The reaction rate was thus reduced. Similar
trend was reported in the previous study, in which a beaker with irradiation of laser was
used as the photoreactor [38]. This phenomenon was observed in different reaction
systems with different light sources and reactors, indicating its universality in
photocatalytic reactions.
Fig. 11. The effect of Phenyl disulfide concentration on the reaction. Reaction
time (a) test tube 2 h (b) microreactor 1 h (other experiment conditions：60℃, 0.15M
-
Styrene, 3 mol% photocatalyst Acr+-Mes ClO4 )
The evaluation of yield to 2-phenylethanol as function of phenyl disulfide
concentration is shown in Fig. 11. When the content of phenyl disulfide was lower than
20%, the reaction rate increased almost linearly with the increasing content of phenyl
disulfide. This promoting effect was much less pronounced when the content of phenyl
disulfide exceeded 20%.
18

Scheme 2. Catalytic cycle for the anti-Markovnikov hydration of styrene
Scheme 2 shows the reaction mechanism of the anti-Markovnikov hydration of
styrene, which was discussed by Lei [11]. Firstly, the acridinium photocatalyst
(substance 3) is excited by visible light, and then quenched by the alkene (substance 1)
through a single-electron transfer (SET) process to generate alkene radical cation
intermediate (substance 10) and acridine radical (substance 5). Then, alkene radical
cation takes anti-Markovnikov addition of water leading the formation of distonic
radical cation (substance 11). At the same time, the phenyl disulfide (substance 9)
photolytic cleavages to thiophenol radical (substance 6), which reacts with acridine
radical (substance 5) to complete the photocatalytic cycle. The protonation of generated
thiophenol anion (substance 7) yields thiophenol (substance 8). The distonic radical
cation (substance 11) is firstly deprotonated and then reacts with thiophenol (substance
8) through hydrogen atom transfer (HAT) process to form alcohol products (substance
2). The thiophenol (substance 8) converts to thiophenol radical (substance 6) through
HAT process, which reversibly converts to phenyl disulfide (substance 9) leading to the
complete photocatalytic cycle. Besides the photocatalytic cycle, the produced styrene
cationic intermediate (substance 10) also undergoes an addition reaction with styrene,
19

resulting in the corresponding 1-phenyl-1,2,3,4-tetrahydronaphthalene (substance 13).
This might be the reason why the yield to 2-phenylethanol reached a plateau in the both
reactors when the content of Phenyl disulfide was above 20%.
4. Conclusion
In this study, the continuous flow production of 2-phenylethanol by visible light
catalyzed anti-Markovnikov hydration of styrene was realized for the first time using
PFA as microreactor. In parallel, a test tube was used as a conventional batch reactor to
compare the performance of microreactor.
Compared with planar LED array, the annular LED could greatly shorten the
reaction time and increase the net turnover frequency (TOF). Using the same annular
LED, the reaction time required by the microreactor was half that of the test tube. The
increasing reaction temperature enhanced the radial mixing, leading to an increase of
the yield to 2-phenylethanol per unit time in both reactors. Moreover, under all studied
reaction temperatures (25-70℃), the microreactor offered a twofold yield to 2-
phenylethanol as compared to test tube, which could be attributed to its higher
efficiency in light utilization. Ultimately, through the optimization of light source shape,
reaction temperature and other reaction conditions, the required reaction time was
successfully reduced from initial 20 hours to < 2 hours.
In both reactors, the increasing substrate concentration resulted in the addition
reaction of styrene carbocation intermediates with styrene, which reduced the
selectivity of 2-phenylethanol. The maximum productivity obtained in this study was
0.049 mol/(L.h) and 0.122 mol/(L.h), respectively in the test tube and microreactor.
Therefore, the present microreactor achieved a 34 times higher productivity of 2-
phenylethanol than the reported value (0.0036 mol/(L.h)) in the open literature.
Furthermore, it was found out that the optimal concentration of photosensitizer Acr+-
-
Mes ClO4 was 2 %. Regarding the HAT catalyst phenyl disulfide, increasing its
concentration within the range of 0-20 % significantly promoted the reaction.
The present work showed that the continuous flow microreactor could be a
20

promising alternative for the 2-phenylethanol production through visible light catalyzed
styrene anti-Markovnikov hydration. The addition reaction between styrene cationic
intermediates with styrene remained as one of the most important drawbacks of this
reaction. A specific designed microreactor other than PFA tubing might be required in
the future to enhance the HAT process of the photocatalytic cycle, so as to increase
further the product yield.
Author Statement
Yuhang Chen: Methodology, Investigation, Writing - Original Draft; Jie
Zhang: Verification, Writing-Review & Editing; Zhiyong Tang:
Conceptualization, Supervision, Funding acquisition; Yuhan Sun: Supervision
Declaration of interests
The authors declare that they have no known competing financial interests or personal
relationships that could have appeared to influence the work reported in this paper.
Acknowledgments
This work was supported by the Youth Innovation Promotion Association of
Chinese Academy of Sciences and the Key Technical Personnel of Chinese Academy
of Sciences, the Ministry of Science and Technology of China (grant
2016YFA0602603). The work was also supported by Frontier Scientific Research
Project funded by Shell under contract No. PT19253.
21

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