(542c) Visible Light Driven Anti-Markovnikov Hydration of Styrene to 2-Phenylethanol in Continuous Flow Microreactor

Introduction

2-phenylethanol (2PE), which is an aromatic
alcohol with a mild rose fragrance, is a key molecule in the fragrance and food
industries. The traditional production method of 2PE involves multi-step
chemical reactions, which require high temperature, strong acid, strong alkali
and other harsh conditions. Furthermore, it is very difficult to separate the
by-products of the reactions, leading to an increase in overall producing cost.
Visible light catalyzed anti-Marko addition of olefin has the characteristics
of less by-products and mild reaction conditions[1]. However, the required reaction time is up
to ten or even dozens of hours. Like large number of other reported photocatalytic
reactions, it is still very challenging to scale up this reaction in
traditional batch reactors due to limited mass and photo transfer issues.

The continuous flow microreactor could be a
promising alternative to circumvent the above common drawbacks of batch
photoreactors because of its larger specific surface and shorter light path. Herein,
for the first time, we attempt to synthesis 2PE through Anti-Marko hydration of
styrene in continuous microreactor system with comparison of batch reactor. The
effects of light source, reaction temperature, substrate concentration and
catalyst concentration were examined experimentally so as to optimize the
reaction conditions and better understand the reaction mechanism.

Experimental

In the present work, the continuous flow
microreactor consisted of PFA capillary with 1mm in inner diameter (total
reaction volume 4 mL) and blue LED irradiation. The schematic diagram of the
reaction platform is shown in Figure 1. The raw materials are styrene and
deionized water, the solvent is acetonitrile, and the catalyst is 9-trimethylene10-methyl
acridine perchlorate and diphenyl
disulfide. For each test, the prepared reactant mixture was pumped into
micoreactor by a syringe pump, and the products were collected and analyzed by
GC-MS. For comparison, batch tests were also conducted using 2 mL reactant mixture in lab test tube under blue LED
irradiation.

Figure 1. Schematic diagram of continuous flow
microreactor platform

Results and discussion

Figure 2 compares the 2PE yield with
different light sources and reactors. For batch reactor, replacing the plat LED
by annular LED could shorten the reaction time from 24 hr to ~6 hr, indicating
that the reaction rate was largely increased by increasing received radiation[2]. As for microreactor system, with
annular LED, the 2PE yield reached maximum (62%) at 4 hr, then it slightly
declined in 6 hr. Also, it can be seen from Figure 1 that the mircroreactor
yielded much more 2PE than tube reactor in the first 3 hrs, which can be
explained by more uniform light distribution in microchannels.

Figure
2. Effect of light sources and reaction system on yield of 2PE (Reaction
conditions: styrene 0.15 M, Acr⁺-Mes ClO₄^- 3
mol%, Ph-S-S-Ph 20 mol%, reaction temperature 25 ËÎÌå">¡æ.)

With the same reaction time 1hr, the effect
of reaction temperature on the 2PE yield is illustrated in Figure 3. As
expected, the 2PE yield was significantly favored by increasing temperature
from 25¡æ to 70¡æ for the both microreactor and
batch systems,. The main reason
is that the increasing temperature accelerates molecular thermal motion, and
thus increases the reaction rate. Nevertheless, it should be noted that
long-term operation of LEDs at high temperature would shorten their lifetime
and also affect the emission wavelength. Moreover, it
can be seen from Figure 3 that as compared to batch system, the 2PE yield was doubled in microreactor system at each reaction
temperature, further confirming its advantages.

Figure
3. Effects of reaction temperature on the 2PE yield in microreactor system (Reaction
conditions: styrene 0.15 M, Acr+-Mes ClO4- 3 mol%, Ph-S-S-Ph 20mol%, reaction
time 1 hr.)

Figure 4 shows the trend of 2-phenylethanol yield for two different
initial styrene concentrations. Increasing the styrene concentration from 0.15M
to 0.3M led to a lower yield of 2PE. The peak of 1-phenyl-1,2,3,4-tetrahydronaphthalene
was detected on GC-MS, and its
area was larger when initial 0.3M styrene was applied. Therefore, we could conclude that the
increasing styrene concentration will result in an increase of polymerization
between styrene, which competes with the formation of 2PE. Moreover, we can
notice that the 2PE yield
remained almost constant after 1 hr or 1.5 hr for the both cases, indicating
that the reaction equilibrium was reached.

Figure 4. Effect of substrate concentration on
the 2PE yield in microreactor system (Reaction conditions: styrene 0.15 M, Acr+-Mes ClO4- 3 mol%,
Ph-S-S-Ph 20mol%, temperature 60¡æ.)

Conclusions

In this study, the continuous production of
2PE from Anti-Markovnikov hydration of styrene was realized for the first time
by using PFA capillary
microreactor. After the optimization of light source, reaction temperature and
other reaction conditions, the reaction time was successfully reduced from the
24 hr to 1 hr. The increasing styrene concentration led to the polymerization
of styrene carbocation intermediates, resulting in a lower selectivity of 2PE. Therefore,
it is worthwhile to design a suitable structured microreactor so as to reduce
the potential polymerization through enhanced mass transfer. The overall
production capacity could then be further improved.

References

[1] X. Hu, G. Zhang, F. Bu, A.
Lei, Visible-Light-Mediated Anti-Markovnikov Hydration of Olefins ACS Catalysis,
(2017) 6.

[2] C.C. Le, M.K. Wismer, Z.C.
Shi, R. Zhang, D.V. Conway, G. Li, P. Vachal, I.W. Davies, D.W.C. MacMillan, A
General Small-Scale Reactor To Enable Standardization and Acceleration of
Photocatalytic Reactions, ACS Cent Sci, 3 (2017) 647-653.