Green benzylation of sodium salicylate by phase-transfer catalysis with

third-liquid phase in a continuous two-phase-ow reactor

Hung-Ming Yang *, Yu-Shoh Huang
Department of Chemical Engineering, National Chung Hsing University, Taichung 402, Taiwan
1. Introduction
Phase-transfer catalysis is an effective technology in organic
synthesis, giving a high conversion and good product selectivity at
mild conditions for the reactions of two mutually insoluble
reactants, and is widely applied in pharmaceuticals, avors,
perfumes, dyes, environmental processes, etc. (Starks et al.,
1994) The main feature of phase-transfer catalysis is that a highly
active intermediate would be formed and transported between
phases to conduct the intrinsic reaction. The reaction systems by
phase-transfer catalysis can be divided into several categories, i.e.
liquidliquid, solidliquid, gasliquid, solidliquidliquid, and tri-
liquid types, among which the liquidliquid PTC systems are
mostly studied previously. In liquidliquid PTC systems, strong
alkali compounds are commonly employed to accelerate the
reaction (Wang and Liu, 2008), but the liquidliquid PTC systems
somewhat have the difculties in the separation of catalyst from
the reaction mixture, and some side reactions might be present.
Suchdrawbacks can be overcome by triphase catalysis, third-liquid
phase-transfer catalysis (Yang and Wu, 2003), PTC in a membrane
reactor (Wu and Wu, 2008), or the combination of PTC and
ultrasound irradiation (Wang and Rajendran, 2007; Yang and
Chen, 2009). In a tri-liquid system, the reaction is conducted by a
viscous layer where a catalytic intermediate is highly concentrat-
ed. This viscous layer is called the third-liquid phase. Since the
third-liquid phase-transfer catalysis (TLPTC) behaves the char-
acteristics of high reaction rates at mild conditions, without using
aprotic or halide-containing solvents, easier separation of the
product and the catalyst, and easy catalyst recovery, it is an
environmentally benign technology in organic synthesis.
In 1984, Neumann and Sasson investigated the isomerization of
allylanisole using polyethylene glycol as the catalyst, and found
that a third phase was formed between the aqueous and the
organic phases (Neumann and Sasson, 1984). Later, quaternary
onium salts were reported to be able to form the third-liquid
phase under specic conditions; the overall reaction rate was
rapidly accelerated with the third-liquid phase, compared with
that conducting in a liquidliquid system (Mason et al., 1991;
Wang and Weng, 1988, 1995). In general, factors inuencing the
formation of the third-liquid phase include the amounts and types
of phase-transfer catalyst, aqueous reactant and extra inorganic
salts, molecular structure of reactants, polarity of organic solvents,
and the interaction between ingredients (Huang and Yang, 2005;
Yadav and Reddy, 1999). In TLPTC, the main reaction usually occurs
in the third-liquid phase where the catalytic intermediate reacts
with the organic reactant that transferred from the organic phase
into the third-liquid phase. Thus, the catalytic intermediate
incorporating with the interfacial characteristics, such as the
interfacial tensions between phases, play important roles in TLPTC
(Lin and Yang, 2005; Yang and Li, 2006; Yang and Huang, 2007).
Journal of the Taiwan Institute of Chemical Engineers 42 (2011) 265270
A R T I C L E I N F O
Article history:
Received 7 May 2010
Received in revised form 6 July 2010
Accepted 11 July 2010
Keywords:
Third-liquid phase
Phase-transfer catalysis
Benzyl salicylate
Two-phase ow
A B S T R A C T
The synthesis of benzyl salicylate frequently used in cosmetics was investigated by third-liquid phase-
transfer catalysis (TLPTC) in a continuous two-phase-ow reactor. This reactor was designed in a way to
keep the third-liquid phase residing in the middle part with the aqueous and organic phases owing
through it countercurrently. To prevent the entrainment of the catalyst into outlet streams, two
membranes were installed in the reactor with a lipophilic type in the upside and a hydrophilic one in the
downside of the reaction zone. With 0.025 mol of tetrabutylphosphonium bromide, 0.125 mol of NaBr
and 0.67 M of sodium salicylate in the aqueous phase to form the third-liquid phase, the yield of benzyl
salicylate in the organic outlet was 82% at steady-state for the conditions of 0.33 Mof benzyl bromide in
n-heptane, space time at 290 min, stirring speed at 300 rpm and temperature at 70 8C. The effects of
various operating parameters were explored and the distributions of the catalyst between phases after
reaction were analyzed. A kinetic model concerning the two-phase ow was proposed to describe the
overall reaction. The results show that the green benzylation of sodium salicylate by TLPTC in a
continuous two-phase-ow reactor was developed.
2010 Taiwan Institute of Chemical Engineers. Published by Elsevier B.V. All rights reserved.
* Corresponding author. Tel.: +886 4 22840510x609; fax: +886 4 22854734.
E-mail address: hmyang@dragon.nchu.edu.tw (H.-M. Yang).
Contents lists available at ScienceDirect
Journal of the Taiwan Institute of Chemical Engineers
j our nal homepage: www. el sevi er . com/ l ocat e/ j t i ce
1876-1070/$ see front matter 2010 Taiwan Institute of Chemical Engineers. Published by Elsevier B.V. All rights reserved.
doi:10.1016/j.jtice.2010.07.012
In the past, the investigations of catalytic reactions by TLPTC
were mostly performed in a batch reactor. The continuous-ow
reactor with three liquid phases coexisted was seldomreported for
TLPTC (Weng et al., 1997; Yang and Peng, 2010). The aim of the
present study is to develop a green process of synthesizing benzyl
salicylate, which is frequently used in cosmetics such as a xative
in perfumes, in sunscreen preparations, etc., via TLPTC in a
continuous two-phase-ow reactor. The phenomena of TLPTC in
continuous operation were explored.
2. Experimental
The aqueous reactant sodium salicylate (ArCOONa, 99.5
+
%)
from SHOWA was used without further treatment. Tetra-n-
butylphosphonium bromide (TBPB or QBr in general), tetra-n-
butylammonium bromide (TBAB), tetra-n-butylammonium iodide
(TBAI), Benzyltributylammonium bromide (BTBAB), benzyl bro-
mide (RBr), the desired product benzyl salicylate (ArCOOR), and
other reagents are all reagent-grade chemicals from SHOWA,
ACROS, TEDIA, Lancaster and TCI.
2.1. Formation and determination of the third-liquid phase
The main constituent in the third-liquid phase is the catalytic
intermediate. In the present system, the catalytic intermediate
tetra-n-butylphosphonium salicylate (ArCOOQ) was prepared and
used in the determination of third-liquid phase. The preparation
procedure was the same with that in the previous study (Yang and
Li, 2006). The third-liquid phase accompanied with portions of the
aqueous and organic phases was introduced in the reactor to start
up the reaction.
After the reaction system was shut down, the content in the
reactor was discharged to separate the third-liquid phase from the
aqueous and organic phases. To analyze ArCOOQin the third-liquid
phase, a denite amount of de-ionized water was introduced into
the third-liquid phase. ArCOOQ in this mixture was then extracted
by chlorobenzene three times; subsequently an aliquot sample of
the chlorobenzene solution was analyzed by HPLC. The amount of
tetra-n-butylphosphoniumcation (denoted as Q
+
) was determined
by Volhards method. In a waterchloroform system, sodium
tetraphenyl borate (0.05N of Na
+
TBP

) and bromophenol blue

(0.2% in ethanol) were used as the titrant and the indicator,
respectively. When the end point is reached, the color of the
chloroform layer will change from blue to colorless.
2.2. The continuous two-phase-ow reactor system
The two-phase-ow reactor was designed to let the aqueous
and organic phases ow countercurrently and to keep the third-
liquid phase residing in the middle part. For preventing the loss of
third-liquid phase entrained to the outlet streams, two membranes
were installed with the hydrophobic type (PTFE membrane lter,
0.5 mm of pore size, from ADVANTEC MFS, Inc., USA) at upside and
the hydrophilic type (Nylon membrane lter, 0.45 mmof pore size,
from WHATMAN, England) at downside of the reaction zone. The
temperature in the reactor was controlled by jacketed water with
thermostat. Within the reaction zone, a bafe was installed to
assist the mixing of various phases. The schematic ow diagramof
the continuous two-phase-ow TLPTC process is shown in Fig. 1.
2.3. Kinetic measurements
The reaction scheme of the third-liquid phase-transfer cata-
lyzed esterication of sodium salicylate with benzyl bromide to
synthesize benzyl salicylate was as follows:
Before starting a kinetic run, the required concentrations of the
aqueous and organic solutions (each with 300 cm
3
of solution)
were rst prepared. A portion of this aqueous solution (87 cm
3
)
was adapted to form the third-liquid phase by reacting with the
required quantity of phase-transfer catalyst. Introducing the above
mixture and the required concentration of RBr into the reaction
zone by pumping, balancing the aqueous and organic streams
between the inlet and outlet, then the continuous kinetic run was
activated. The ow rates of the aqueous and organic streams were
controlled at the desired values. In general, the steady-state
operation can be achieved after 5 h on stream. The product yield in
the organic outlet, the catalyst and catalytic intermediate after
reaction were analyzed. The product yield is dened as the outlet
concentration of product ArCOOR in the organic phase at steady-
state divided by the inlet concentration of reactant RBr in the
organic phase. The organic and aqueous samples were withdrawn
in the sampling port of the process lines at each chosen time. The
amount of Q
+
in the third-liquid phase was determined by the
Volhards method. ArCOOR and ArCOOQ were analyzed by HPLC.
The organic sample and the third-liquid sample were diluted into
4 cm
3
of acetonitrile and analyzed with internal method using
HPLC with C-18 (5-mm) column and variable-wavelength UV
detector at 254 nm. The ow rate of eluent was 1.0 cm
3
/min in a
volume ratio of acetonitrile/water to be 70/30.
3. The kinetic model
For the third-liquid phase-transfer catalyzed esterication, the
key step is the formation of the catalytic intermediate, which is
produced from the reaction of ArCOONa and catalyst QBr in the
aqueous phase. The reaction mechanism is shown as follows.

Fig. 1. Schematic ow diagram of the continuous TLPTC reaction system. T1:
feedstock of organic phase, T2: feedstock of aqueous phase, T3: storage tank of
organic phase, T4: storage tank of aqueous phase, T5: make-up catalyst, P1, P2, P3:
feeding pump, R: reactor, J: jacketed heat exchanger, M1: Nylon membrane lter,
M2: PTFE membrane lter, C1, C2: inlet and outlet of circulating water.
H.-M. Yang, Y.-S. Huang / Journal of the Taiwan Institute of Chemical Engineers 42 (2011) 265270 266
The reaction and mass-transfer steps in the overall reaction are
(a) reaction of QBr and ArCOONa in the aqueous phase to form
ArCOOQ which is then distributed into the third-liquid phase,
ArCOONa aq QBr aq ArCOOQ aq NaBr aq;
ArCOOQ aq ArCOOQ th
with the distribution relation
K
ArCOOQ

C
th
ArCOOQ
C
aq
ArCOOQ
; (1)
(b) transfer of RBr from the organic phase into the third-liquid
phase,
RBr org RBr th
with the distribution relation
K
RBr

C
th
RBr
C
org
RBr
; (2)
(c) intrinsic reaction of ArCOOQ and RBr in the third-liquid phase,
ArCOOQth RBrth ! ArCOORth QBrth;
with the reaction rate of RBr
r
th
RBr
kC
th
ArCOOQ
C
th
RBr
; (3)
where k is the reaction rate constant.
(d) transfer of the regenerated QBr fromthe third-liquid phase into
the aqueous phase,
QBr th QBr aq
with the distribution relation
K
QBr

C
aq
QBr
C
th
QBr
; (4)
(e) transfer of the product ArCOORfromthe third-liquid phase into
the organic phase with the distribution relation,
K
ArCOOR

C
th
ArCOOR
C
org
ArCOOR
: (5)
Since the main reactionis conductedby ArCOOQand RBr, taking
material balance for RBr in the continuous-ow system at steady-
state gives
v
org
C
RBr;0
v
org
C
org
RBr
r
th
RBr
V
th
; (6)
where V
th
is the volume of third-liquid phase, and v
org
is the
volumetric ow rate of the organic phase.
Combining Eqs. (6) and (3), we have
v
org
C
org
RBr;0
v
org
C
org
RBr
kC
th
ArCOOQ
C
th
RBr
V
th
kC
th
ArCOOQ
K
RBr
C
org
RBr
dV
org
(7)
where V
org
is the volume of organic phase in the reactor and
d = V
th
/V
org
. From experimental observations, the variation of
molar ratio of ArCOOQin the third-liquid phase to initial QBr added
was small after reaching the steady-state (e.g. the ratios 65.4% in
300 min and 60.6% in 480 min of reaction), and C
th
ArCOOQ
can be
regarded as a constant for simplicity. Thus, Eq. (7) can be
rearranged to give
C
org
RBr
C
org
RBr;0

1
1 k
app
t
org
; (8)
where t
org
V
org
=v
org
and k
app
kdC
th
ArCOOQ
K
RBr
:
The apparent reaction rate constant k
app
is functions of intrinsic
reaction rate, volume of third-liquid phase, distribution of RBr and
concentration of ArCOOQin the third-liquid phase. At steady-state,
the product ArCOOR in the organic outlet comes from the
consumption of RBr in the organic stream. Thus, the material
balance for the conversion of RBr into ArCOOR in the owsystemis
v
org
C
org
RBr;0
v
org
C
org
RBr
v
org
C
org
ArCOOR
: (9)
dening the product yield Y
S
in the organic outlet at steady-state,
Y
S
C
org
ArCOOR
=C
org
RBr;0
, Eq. (9) can be rearranged to give
1 Y
S

C
org
RBr
C
org
RBr;0
: (10)
by substituting Eq. (10) into Eq. (8) and rearranging, we can get the
performance equation at steady-state as
k
app

Y
S
1 Y
S
t
org
: (11)
the apparent rate constant k
app
can be obtained from Eq. (11) and
used to describe the reaction system. The apparent activation
energy E
app
can be obtained from the Arrhenius equation of k
app
,
k
app
= A exp( E
app
/RT).
4. Results and discussion
In performing the continuous two-phase-ow TLPTC reaction,
the third-liquid phase should be separately prepared prior to the
reaction. This was achieved by the reaction of the catalyst and
sodiumsalicylate in the aqueous solution with an addition of extra
inorganic salts. To start up a run, the third-liquid phase
accompanying with the aqueous and organic phases was intro-
duced into the reactor simultaneously, following the steps as
described in Section 2. The product yield in the exit, the
distribution of Q
+
in the reactor, and the catalytic intermediate
in the third-liquid phase after reaction were analyzed.
4.1. Effect of ow rate of the organic phase
In TLPTC, the intrinsic reaction of ArCOOQ with RBr mainly
occurs in the third-liquid phase. In a continuous-ow system, the
ow rate of the organic phase determines the time of the reactant
residing in the reaction zone. The extent of overall reaction and
distributions of the catalyst between the aqueous, the organic and
the third-liquid phases would be affected by the organic ow rate.
Fig. 2 shows the average yields of benzyl salicylate in the organic
exit stream after steady-state (>5 h of on stream) for various
organic ow rates. The space time t
org
for the organic stream was
estimated by using Eq. (8) to be 290, 217.5, 174, and 145 min for
the organic ow rates (cm
3
/min) at 0.3, 0.4, 0.5, and 0.6,
respectively. The product yields were obtained to be 82%, 71%,
60%, and 34% at 0.3, 0.4, 0.5, and 0.6 cm
3
/min of organic ow rate,
respectively. The apparent reaction rate constant k
app
was
estimated using Eq. (11) by averaging the yield after steady-state,
H.-M. Yang, Y.-S. Huang / Journal of the Taiwan Institute of Chemical Engineers 42 (2011) 265270 267
and approximately linearly increased with increasing the space
time of the organic stream, as shown in Fig. 3. The results showthat
the proposed kinetic model can be used to describe the TLPTC in
continuous-ow mode.
When the intrinsic reaction was conducted in the third-liquid
phase, the catalyst would be regenerated and distributed into the
organic phase depending on the type of catalyst used, thus the
amount of the catalyst retained in the third-liquid phase also
reects the extent of the intrinsic reaction. In addition, some of the
catalyst distributed into the organic streammight be entrained out
of the reactor. Fig. 4 shows the distribution of catalyst Q
+
in
different phases. The ratios for Q
+
(third)
/QBr
,0
were 88.2%, 81.2%,
79.5%, and 77.1% for organic ow rates (cm
3
/min) at 0.3, 0.4, 0.5,
and 0.6, respectively. The catalyst in the third-liquid phase
decreased with decreasing space time, revealing that a higher
ow rate resulted in more catalyst owing out of the reactor.
Before starting the reaction, the volume of the third-liquid phase
was measured to be 15 cm
3
at the conditions of 87 cm
3
of aqueous
solution containing 0.67 M of ArCOONa, 0.083 M of TBPB and
4.17 Mof NaBr. After terminating the reaction in 5 h, the volume of
the third-liquid phase within the reactor was measured for different
organic ow rates to be 10.5 cm
3
for 0.3 cm
3
/min, 11.5 cm
3
for
0.4 cm
3
/min, 11.0 cm
3
for 0.5 cm
3
/min, and 10.5 cm
3
for 0.6 cm
3
/
min. It showed that much more catalyst would be kept in the third-
liquid phase for a larger space time. Furthermore, the catalytic
intermediate in the third-liquid phase within the reactor also
increased with decreasing organic ow rate, i.e. ArCOOQ
(third)
/QBr
,0
being60.6%, 54.6%, 49.7%, and50.3%for organicowrates (cm
3
/min)
at 0.3, 0.4, 0.5, and 0.6, respectively. Ahigher organic owrate led to
much catalyst and catalytic intermediate distributed into the
organic phase and subsequently owing out of the reactor.
4.2. Effect of the molar ratio of RBr to ArCOONa
The concentration of RBr affects the intrinsic reaction rate of
ArCOOQ and RBr in the third-liquid phase. In the conditions of
0.3 cm
3
/min of organic ow rate (t
org
= 290 min), 0.3 cm
3
/min of
aqueous owrate, 0.67 Mof ArCOONa, 0.025 mol of TBPB, 1.25 mol
of NaBr and using n-heptane as the solvent, the proles of product
concentration at 70 8C for different feeding concentrations of RBr
are shown in Fig. 5. The amount of the product ArCOOR was
increased as increasing the amount of RBr employed. The product
yields in the organic phase based on RBr and the apparent reaction
rate constants k
app
were obtained as 71% (0.0084 min
1
), 82%
(0.0162 min
1
), 81% (0.0138 min
1
) and 80% (0.0149 min
1
) for
RBr concentration at 0.5 M, 0.33 M, 0.25 Mand 0.17 M, respective-
ly. Regardless of almost the same yield for the feeding ratio (RBr/
ArCOONa) less than 0.5, the produced ArCOOR actually increased
with increasing the amount of RBr.
The volume of the third-liquid phase was reduced after 5 h of on
stream because some of the catalyst was entrained to the outlet
streams. With the concentration of RBr up to 0.5 M, the
entrainment of catalyst Q
+
was observed to be 12.8% of Q
+
/QBr
,0
in the outlet stream, as shown in Fig. 6. A higher feeding
concentration of RBr enhanced the reaction rate of RBr with
ArCOOQ, leading to a faster consumption rate of ArCOOQ in the
third-liquid phase. From the results in Fig. 6, the ratio of
ArCOOQ
(third)
to QBr
,0
decreased from 0.8 at 0.17 M of RBr to
0.45 at 0.5 Mof RBr, almost in a linear relation of decline. However,

Fig. 2. Proles of product yield for different organic ow rates; 0.67 M of ArCOONa
in water, 0.33 M of RBr in n-heptane, 1.25 mol of NaBr, 0.025 mol of TBPB, 70 8C,
300 rpm, 0.3 cm
3
/min of aqueous ow rate; organic ow rate (cm
3
/min): (^) 0.3,
(&) 0.4, (4) 0.5, (*) 0.6.

Fig. 3. Plot of k
app
vs. space time; 0.67 M of ArCOONa in water, 0.33 M of RBr in n-
heptane, 1.25 mol of NaBr, 0.025 mol of TBPB, 70 8C, 300 rpm, 0.3 cm
3
/min of
aqueous (or organic) ow rate.

Fig. 4. Dependence of organic ow rate on the distribution of catalyst between
phases; molar ratio: (*) Q
+
(third)
/QBr
,0
, (&) Q
+
(aq)
/QBr
,0
, (4) Q
+
(org)
/QBr
,0
, (^)
Q
+
(exit)
/QBr
,0
, (~) ArCOOQ
(third)
/QBr
,0
.
H.-M. Yang, Y.-S. Huang / Journal of the Taiwan Institute of Chemical Engineers 42 (2011) 265270 268
the catalyst that entrained by the outlet streams can be easily
separated and recovered for use.
4.3. Effect of phase-transfer catalyst and temperature
Four phase-transfer catalysts TBAB, TBPB, TBAI, and BTBAB
were selected to test their performance in a continuous-ow
reactor. For the conditions of ArCOONa at 0.67 M, RBr at 0.33 M,
0.125 mol of NaBr, 0.0125 mol of PTC, and the space time at
290 min, the product yield and the apparent reaction rate constant
were 65% (0.0065 min
1
) for TBAB, 82% (0.0162 min
1
) for TBPB,
76% (0.011 min
1
) for TBAI, and 77% (0.0116 min
1
) for BTBAB, as
shown in Table 1. The order of catalytic activity in the continuous
two-phase-ow system for the tested catalysts is
TBPB > BTBAB > TBAI > TBAB. TBPB possessed the highest activity
in the continuous operation. This might be due to that TBPB has a
higher hydrophobic property to keep much of the catalyst (88.2% of
Q
+
(third)
/QBr
,0
) resided in the third-liquid phase, with only 0.8% of
Q
+
(third)
/QBr
,0
in the exit streams when a sufcient amount of NaBr
was used. WithTBABas the catalyst, 57%of Q
+
(third)
/QBr
,0
was kept in
the reactor but with3.8%of Q
+
/QBr
,0
entrainedto the outlet streams,
leading to a lower activity of catalyst. With BTBAB as the catalyst,
although13.5%of Q
+
/QBr
,0
was distributedtothe outlet streams, but
74.8% of Q
+
/QBr
,0
still retained in the third-liquid phase to give a
product yield of 77%.
Using TBPB as the catalyst for different reaction temperatures,
the proles of product yield versus time are showninFig. 7. It is seen
that the steady-state operation was achieved after about 5 h of on
streamfor 50, 60, and 70 8C, and a slightly longer time needed (6 h)
for 40 8C. The average product yields and k
app
were 51%
(0.005 min
1
) for 40 8C, 73% (0.0091 min
1
) for 50 8C, 78%
(0.0124 min
1
) for 60 8C, and 82% (0.0162 min
1
) for 70 8C. The
apparent activation energy for TBPBwas calculated as 8.91 kcal/mol
with k
app
= 8.76 10
6
exp( 8910/RT). In addition, the volume of
thethird-liquidphasebeforereactionwas 15 cm
3
; after reaction, the
volumes of the third-liquid phase were reduced to 14 cm
3
for 40 8C,
13 cm
3
for 50 8C, 12 cm
3
for 60 8C, and 10.5 cm
3
for 70 8C. The
volume of reduction in the third-liquid phase increased with
increasing the reaction temperature due to the solubility of catalyst

Fig. 5. Effect of RBr concentration on the product yield; 0.67 Mof ArCOONa in water,
1.25 mol of NaBr, 0.025 mol of TBPB, RBr in n-heptane, 300 rpm, 70 8C, ow rate
(aqueous or organic phase) at 0.3 cm
3
/min; feeding concentration of RBr (M):
(^) 0.17, (&) 0.25, (4) 0.33, (*) 0.50.

Fig. 6. Dependence of RBr concentration on the distribution of catalyst between
phases; molar ratio: (*) Q
+
(third)
/QBr
,0
, (&) Q
+
(aq)
/QBr
,0
, (4) Q
+
(org)
/QBr
,0
,
(^) Q
+
(exit)
/QBr
,0
, (~) ArCOOQ
(third)
/QBr
,0
.
Table 1
Effects of PTC on the product yield and distribution of Q
+
after reaction.
PTC (mol) Q
+
(third)
/QBr
,0
within
the reactor (%)
Q
+
(aq)
/QBr
,0
within
the reactor (%)
Q
+
(org)
/QBr
,0
within
the reactor (%)
Q
+
/QBr
,0
in outlet
streams (%)
Product
yield
a
(%)
10
2
k
app
(min
1
)
TBPB 88.2 9.6 1.4 0.8 82 1.62
TBAB 57.0 37.4 1.8 3.8 65 0.65
BTBAB 74.8 10.1 1.6 13.5 77 1.16
TBAI 51.6 39.2 0.0 9.2 76 1.10
Conditions: 0.67Mof ArCOONa in water, 0.33Mof RBr in n-heptane, 1.25mol of NaBr, 0.025mol of PTC, stirring at 300rpm, 708C, aqueous or organic owrate at 0.3cm
3
/min.
a
Average value based on RBr after 5h of duration (at steady-state).

Fig. 7. Proles of product yield for different temperatures; 0.67 M of ArCOONa in
water, 0.33 M of RBr in n-heptane, 1.25 mol of NaBr, 0.025 mol of TBPB, 300 rpm,
0.3 cm
3
/minof aqueous (or organic) owrate; temperature (8C): (^) 40, (*) 50, (4)
60, (&) 70.
H.-M. Yang, Y.-S. Huang / Journal of the Taiwan Institute of Chemical Engineers 42 (2011) 265270 269
in the aqueous phase increased at a higher temperature, resulting in
the decline of the temperature sensitivity on the reaction rate.
4.4. Effect of inorganic salts
A signicant factor in forming the third-liquid phase is the type
andamount of inorganic salts added. Four salts NaBr, KBr, NaI, andKI
were compared. The distribution of Q
+
in the three phases and the
product yield after 5 h of duration are shown in Table 2. The
percentages of Q
+
(third)
/QBr
,0
within the reactor catalyst were 88.2%
for NaBr, 84.8% for KBr, 31.2% for NaI, and 41% for KI. For KI system,
almost half of the catalyst would reside in the aqueous phase within
the reactor. But for NaI system, 20.9% of Q
+
(org)
/QBr
,0
was found to
exist in the organic phases, and that might conduct the intrinsic
reaction in a signicant level. The phenomena of catalyst distribu-
tion determine where the reaction mainly takes place. The product
yields and the apparent reaction rate constants by adding inorganic
salts were 82% (0.0162 min
1
) for NaBr, 71% (0.0082 min
1
) for NaI,
68% (0.0075 min
1
) for KBr, and 62% (0.0057 min
1
) for KI. For the
four testedsalts, the fastest reactionrate was promotedbyNaBr, and
the slowest by KI. This is due to the fact that the iodides (NaI, KI)
convert benzyl bromide into benzyl iodide to induce much more Q
+
solvated in the aqueous phase, and the effective amount of Q
+
in the
third-liquid phase is thus reduced. The results indicate that the
addition of extra inorganic salt is a signicant factor in this
continuous-ow TLPTC esterication system.
5. Conclusions
A green technology in organic synthesis, the third-liquid phase-
transfer catalysis, was developed in a continuous two-phase-ow
reactor for synthesizing benzyl salicylate. The reactor was speci-
cally designed to retain the third-liquid phase in the reaction zone
under the interaction of the countercurrent owof the aqueous and
organic phases. Using an environmentally friendly solvent to
prepare the third-liquid phase, the yield of benzyl salicylate in
the organic outlet reached82%at steady-state. The effects of various
operating parameters were explored and the distributions of the
catalyst between phases after reaction were analyzed. The present
studyprovides aneffective process tosynthesize esters byTLPTCina
continuous two-phase-ow reactor.
Acknowledgment
The authors acknowledge the nancial support of the National
Science Council, Taiwan. (Grant No. NSC 93-2214-E-005-001).
References
Huang, C. C. and H. M. Yang, Kinetics for Benzoylation of Sodium 4-Acetylphenoxide
via Third-Liquid Phase in the Phase-Transfer Catalysis, Appl. Catal. A: Gen., 290, 65
(2005).
Lin, P. J. and H. M. Yang, Kinetics for Etherication of Sodium o-Nitrophenoxide via
Third-Liquid Phase-Transfer Catalysis, J. Mol. Catal. A: Chem., 235, 293 (2005).
Mason, D., S. Magdassi, and Y. Sasson, Role of a Third Liquid Phase in Phase-Transfer
Catalysis, J. Org. Chem., 56, 7229 (1991).
Neumann, R. and Y. Sasson, Mechanism of Base-Catalyzed Reactions in Phase-
Transfer Systems with Poly(ethylene glycols) as Catalysts. The Isomerization of
Allylanisole, J. Org. Chem., 49, 3448 (1984).
Starks, C. M., C. L. Liotta, and M. Halpern, Phase-Transfer Catalysis: Fundamental,
Applications, and Industrial Perspectives, Chapman & Hall, New York (1994).
Wang, M. L. and Y. C. Liu, Kinetic Study of S-Alkylation of 2-Mercaptobenzimidazole
by Allyl Bromide in the Presence of Potassium Hydroxide, J. Chin. Inst. Chem.
Engrs., 39, 587 (2008).
Wang, M. L. and V. Rajendran, Ultrasound Assisted Phase-Transfer Catalytic Epoxi-
dation of 1, 7-Octadiene A Kinetic Study, Ultrason. Sonochem., 14, 46 (2007).
Wang, D. H. and H. S. Weng, Preliminary Study on the Role Played by the Third Liquid
Phase in Phase Transfer Catalysis, Chem. Eng. Sci., 43, 2019 (1988).
Wang, D. H. and H. S. Weng, Phase Transfer Catalytic Reaction between n-Butyl
Bromide and Sodium PhenolateFormation of the Third Liquid Phase and Its
Effect, J. Chin. Inst. Chem. Engrs., 26, 147 (1995).
Weng, H. S., C. M. Wang, and D. H. Wang, A Preliminary Study on a Continuous Flow
Stirred Vessel Reactor for Tri-Liquid-Phase Phase Transfer Catalysis, Ind. Eng.
Chem. Res., 36, 3613 (1997).
Wu, H. S. and Y. K. Wu, Kinetics of Allylation of Phenol Using Quaternary Ammonium
Membranes in a Membrane Reactor, J. Chin. Inst. Chem. Engrs., 39, 29 (2008).
Yadav, G. D. and C. A. Reddy, Kinetics of the n-Butoxylation of p-Chloronitrobenzene
under LiquidLiquidLiquid Phase-Transfer Catalysis, Ind. Eng. Chem. Res., 38,
2245 (1999).
Yang, H. M. and C. H. Chen, Catalytic Esterication of Sodium Salicylate in Third-
Liquid Phase under Ultrasound-Assisted Tri-liquid Phase-Transfer Catalysis, J.
Mol. Catal. A: Chem., 312, 107 (2009).
Yang, H. M. and C. C. Huang, Catalytic Benzoylation of 4-Chloro-3-methylphenol
Sodium Salt in Third-Liquid Phase under Conditions of Phase-Transfer Catalysis,
Ind. Eng. Chem. Res., 46, 7915 (2007).
Yang, H. M. and C. C. Li, Kinetics for Synthesizing Benzyl Salicylate by Third-Liquid
Phase-Transfer Catalysis, J. Mol. Catal. A: Chem., 246, 255 (2006).
Yang, H. M. and G. Y. Peng, Ultrasound-Assisted Third-Liquid Phase-Transfer Cata-
lyzed Esterication of Sodium Salicylate in a Continuous Two-Phase-Flow
Reactor, Ultrason. Sonochem., 17, 239 (2010).
Yang, H. M. and H. S. Wu, Interfacial Mechanism and Kinetics of Phase-Transfer
Catalysis, Catal. Rev.-Sci. Eng., 45, 463 (2003).
Table 2
Effect of PTC and inorganic salts on the distribution of catalyst after reaction.
Inorganic salt Q
+
(third)
/QBr
,0
within
the reactor (%)
Q
+
(aq)
/QBr
,0
within
the reactor (%)
Q
+
(org)
/QBr
,0
within
the reactor (%)
Q
+
/QBr
,0
in outlet
streams (%)
Product
yield
a
(%)
10
2
k
app
(min
1
)
NaBr 88.2 9.6 1.4 0.8 82 1.62
KBr 84.8 12.6 1.5 1.1 68 0.75
NaI 31.2 42.0 20.9 5.9 71 0.82
KI 41.0 50.8 6.4 1.8 62 0.57
Conditions: 0.67Mof ArCOONa in water, 0.33Mof RBr in n-heptane, 1.25mol of salt, 0.025mol of TBPB, stirring at 300rpm, 708C, aqueous or organic owrate at 0.3cm
3
/min.
a
Average value based on RBr after 5h of duration (at steady-state).
H.-M. Yang, Y.-S. Huang / Journal of the Taiwan Institute of Chemical Engineers 42 (2011) 265270 270