4722 Ind. Eng. Chem. Res.

2002, 41, 4722-4732

Continuous Regioselective Enzymatic Esterification in a Simulated

Moving Bed Reactor
Jonathan P. Meissner and Giorgio Carta*
Department of Chemical Engineering, University of Virginia, Charlottesville, Virginia 22904-4741

A simulated moving bed adsorptive reactor (SMBR) has been developed and tested experimentally
to conduct a regioselective enzyme-catalyzed diol esterification in a hexane solvent. The reaction
is equilibrium limited, and accumulation of water on the biocatalyst causes a reduction in
biocatalytic activity. As a result simultaneous removal of water by adsorption on a catalytically
inert ion-exchange resin in Na form has been used to improve conversion. A three-zone SMBR
system was developed for this purpose integrating reaction, adsorption, and regeneration. The
packed beds in the three zones are periodically advanced in a “merry-go-round” fashion to
simulate countercurrent flow. The SMBR allows continuous operation while reducing desorbent
consumption and improving conversion relative to a conventional fixed-bed reactor. A math-
ematical model was developed to simulate the SMBR system based on independent analyses of
adsorption and reaction phenomena. The model takes into account the interplay of these
phenomena and provides a useful tool to understand the effects of process variables and for the
selection of optimum operating conditions.

Introduction shown that catalytically inert ion-exchange resins are

The discovery that certain enzymes, such as lipases,
can also function in nearly anhydrous organic solvents1
has greatly expanded the range of substrates usable in
biocatalytic reactions, spurring a growing interest in
new industrial applications. Much of the industrial
interest stems from the chemospecificity, regioselectiv-
ity, and stereoselectivity that is often exhibited by these
biocatalysts.2-6 Moreover, enzymes are thought to be
more environmentally friendly than many conventional
catalysts and work at moderate temperatures and pH.
Esterifications are among the most industrially in-
teresting reactions in this area.7 However, while, these
reactions are of great interest for the synthesis of flavors
and fragrances, pharmaceutical intermediates, and
specialty chemicals, they are often subject to thermo-
dynamic equilibrium limitations8-10 as well as to loss
of catalytic activity when water produced in the reaction
accumulates on the biocatalyst.11 Thus, in general, the
water produced in these reactions must be controlled
in order to attain high conversions and preserve the
biocatalyst activity.
It has been suggested12,13 that water can be controlled
by limiting its thermodynamic activity in the reaction
mixture, because that in turn controls the reaction
equilibrium and the partitioning of substrates and
products between the reaction mixture and the biocata-
lyst. Several approaches have been proposed to achieve
this, including the use of salt hydrates14 pervaporation
through water-selective membranes,15,16 free and vacuum
evaporation,17 distillation,18 and air sparging.19 Adsorp-
tion onto a water-selective medium has also been
considered by a number of authors17,20 and is of par-
ticular interest because of the ease with which adsor-
bents can be incorporated into packed bed reactors that
are often preferred for enzymatic conversions.21,22 For
example, Mensah et al.11,23 and Migliorini et al.24 have
* Corresponding author. Telephone: (434) 924 6281. FAX:
(434) 982 2658. E-mail: gc@virginia.edu.
10.1021/ie0202625 CCC: $22.00 © 2002 American Chemical Society
Published on Web 08/24/2002
effective for in situ control of water in enzymatic
reactions, with the advantage that removal of the
adsorbed water can be done with a polar solvent,
without having to separate the biocatalyst from the
adsorbent. However, to obtain a continuous operation
of adsorptive reactor, systems that integrate reaction,
separation, and regeneration steps efficiently are desir-
able. Simulated moving bed reactor (SMBR) systems
have been developed for this purpose.
SMBR systems simulate a countercurrent flow of the
adsorbent/catalyst and the fluid phase through the use
of multiple fixed beds advanced in a “merry-go-round”
fashion. The technology draws upon the success of
simulated moving bed separators that are now used
extensively on a large scale25 but incorporates a reactive
component. As such, they retain the advantages of true
countercurrent reactor systems without the operational
complexities of actually moving adsorbent/catalyst par-
ticles.
A number of laboratory studies of SMBR systems
have appeared in the literature in recent years, includ-
ing reactors for the hydrogenation of mesitylene,26-29
for the oxidative coupling of methane,30-32 and for a
number of sulfonic acid resin catalyzed esterifications,
transesterifications, and acetylations.33-35 Some experi-
mental applications to enzyme-catalyzed reactions have
also been studied such as the enzymatic isomerization
of glucose to fructose36 and lipase-catalyzed transes-
terifications,37 and a number of theoretical studies of
adsorptive reactors have been conducted.38-41 However,
despite these studies, no industrial scale applications
of adsorptive SMBR have been reported. It is hoped that
a better understanding of the interplay of adsorptive
and reaction phenomena and the exploration of the
potential for applications in critical fields such as
biocatalysis will allow practical implementation of these
reactors. It should be noted that biocatalytic reactions
are good candidates because the temperature is low so
that adsorption can be effective.

Figure 1. Simulated moving bed reactor concept.
The objective of this work is to determine the suit-
ability of an SMBR system for a reversible regioselective
enzymatic esterification. The reaction considered is the
lipase-catalyzed esterification of propionic acid and
2-ethyl-1,3-hexanediol to form the primary monoester
and water according to
The reaction occurs in a nearly anhydrous hexane
solvent and is equilibrium limited (K ) 0.6 at 22 °C).24
The biocatalyst is Lipozyme IM (Novo Nordisk Bioin-
dustrials, Inc., Franklinton, NC) and consists of a Mucor
miehei lipase immobilized on a macroporous polymeric
support. Direct conversions of diols to their monoester
are of considerable importance as these products have
applications in cosmetics, pharmaceutical intermedi-
ates, and surfactants.2 Biocatalytic routes are often
desirable for these applications because of regulatory
and selectivity considerations.
The Lipozyme biocatalyst used in this work is highly
selective for the primary monoester and exhibits long-
term stability. However, as shown by Migliorini et al.,24
accumulation of water on the biocatalyst reduces its
catalytic activity. Thus, adsorption of water onto the
biocatalyst must be prevented to maintain the highest
reaction rates. Migliorini at al. studied the adsorption-
assisted operation of this reaction by incorporating an
ion-exchange resin as a water adsorbent together with
the biocatalyst in batch and fixed-bed reactors. In situ
water removal was shown to provide two distinct
advantages: it shifted the thermodynamic equilibrium
toward high conversion and it prevented accumulation
of water on the biocatalyst, maintaining high activity.
Since these advantages are realized only during tran-
sient operation of these reactors, the application of an
SMBR system integrating reaction, adsorption, and
regeneration is developed in this work.
SMBR System
The SMBR considered in this work is shown sche-
matically in Figure 1. It consists of three separate zones
with intermediate feed and product withdrawal points.
The acid substrate feed is supplied continuously to zone
III, while the diol substrate feed is supplied continuously
to zone I. A “raffinate” stream containing the ester
product is recovered from zone III, while an “extract”
stream containing the water product and excess diol fed
to the system is withdrawn from zone I. Each zone
Ind. Eng. Chem. Res., Vol. 41, No. 19, 2002 4723
comprises multiple beds, and the inner arrow shows the
direction of bed switching. In practice, of course, this
motion is obtained by the periodic switching of valves.
The switching time, p, is related to the equivalent solid
and liquid velocities in a true countercurrent system by
the following equations:
(1 - )L
js )
u (1a)
p
L
j i ) ui -
u (1b)
p
where  is the bed void fraction, L is the bed length,
and ui is the fluid-phase velocity. The latter is different
in each zone as a result of the addition or withdrawal
of streams.
The role played by the different zones in the SMBR
is as follows. Zone III serves as the reaction/separation
zone. In this zone the acid substrate reacts with the diol
entering from zone II to form the ester and water. The
water produced is adsorbed and is carried upstream by
the solid phase with each successive switch. The bulk
of the adsorbed water is removed in zone I by the diol
substrate, which is fed in amounts in excess of the
stoichiometric reaction requirement. The regenerated
adsorbent is thus returned to zone III. The excess diol
and desorbed water are purged from the system in the
extract stream, which is withdrawn between zones I and
II. A portion of the diol stream emerging from zone I
enters zone II. The function of this zone is to remove
water from the diol, preventing a high water concentra-
tion from entering the reaction/separation zone (zone
III) and preventing the acid and ester produced near
the entrance of zone III from being lost in the extract.
Figure 1 shows two beds in each zone. While more beds
could be added, it has been shown that most of the
benefits of the true countercurrent operation can be
gained even with only a single bed in each zone.
The correct operation of the SMBR requires the
selection of fluid velocities in such a way that the
adsorbed species (e.g., water) move in the appropriate
direction in each zone. Thus, the fluid velocity in the
reaction/adsorption zone must be such as to prevent the
water produced in the reaction from breaking through
in the raffinate. Conversely, the diol feed flow rate must
be sufficiently high so that water will be desorbed in
zone I and move toward the extract withdrawal point.
Finally, the fluid velocity in zone II must be sufficiently
low that water is transported by the solid phase toward
the extract withdrawal point.
Experimental Section
Materials and Methods. Lipozyme IM was obtained
from Novo Nordisk Bioindustrials, Inc., (Franklinton,
NC). The biocatalyst has a particle size of 0.04 ( 0.02
cm and a porosity of 0.53 ( 0.02. The initial water
content of the fresh Lipozyme IM used in this work was
2.4 ( 0.4 mmol/g, determined through weight loss on
drying in an oven at 120 °C.
The adsorbent used in this work is Dowex HCR-W2
in Na+ form (Dow Chemical Company, Midland, MI).
This is a sulfonated, gel-type polystyrene-divinylben-
zene resin with a nominal degree of cross-linking of 8%.
The resin consists of spherical particles 0.04 ( 0.02 cm
in size. It was converted to the sodium form with 1 N
4724 Ind. Eng. Chem. Res., Vol. 41, No. 19, 2002
Figure 2. Simulated moving bed reactor apparatus.
sodium hydroxide, rinsed with deionized distilled water,
and dried in an oven at 120 °C.
Propionic acid (99% purity), 2-ethyl-1,3-hexanediol
(97% purity), and hexane (capillary GC grade) were
obtained from Sigma Chemical Co. (St. Louis, MO). The
feed solutions were kept nearly anhydrous by storing
them under the Dowex adsorbent material.
A 80/100 mesh Chromosorb 101 column (Alltech,
Deerfield, IL) was used with a Hewlett-Packard model
5890A gas chromatograph (thermal conductivity detec-
tion) for analysis.
SMBR Apparatus. A schematic of the SMBR ap-
paratus is shown in Figure 2. For simplicity the diagram
shows only three beds (one per zone), although the
apparatus could accommodate as many as ten beds.
Glass chromatographic columns 1.5 cm in diameter
(Omnifit, Toms River, NJ) were used, each containing
2 g of Dowex resin and 4 g of the Lipozyme biocatalyst.
The two materials were intimately mixed and poured
in the columns. The settled bed height was 7.1 ( 0.1
cm. The total void fraction of these columns was
estimated to be 0.66, based on b ) 0.4 and the porosity
of Lipozyme. Metering pumps with accuracy of (0.01
cm3/min (Eldex A-60-S and Eldex B-100-S, Napa, CA)
were used to feed the acid and diol streams dissolved
in hexane and withdraw the extract stream. The flow
rate of the remaining stream (the raffinate) is deter-
mined by a mass balance. The desired stream routing
is accomplished using rotary stream selector valves
(model C25Z-3180E, Valco Instrument Company, Inc.,
Houston, TX). Check valves (model CV 3000, Upchurch
Scientific, Oak Harbor, WA) are placed between each
column to prevent backflow. Connections between the
columns and valves were made with 1/16 in. PTFE
tubing. Samples were collected from the raffinate and
extract streams at predetermined time intervals. To
prevent evaporation of these samples, a Gilson model
231 autoinjector was modified to automatically collect
the raffinate samples and inject them into septum-
capped glass vials.
Synchronized switching of the valves was accom-
plished using electric actuators (model E10, Valco
Instrument Company, Inc., Houston, TX) interfaced to
a PC-based control system. All experiments were con-
ducted at room temperature 22 ( 2 °C.
Table 1. Experimental Conditions for SMBR Runsa
configuration QD QE QA p
run (NI - NII - NIII) (cm3/min) (cm3/min) (cm3/min) (min)
A 1-1-1 0.77 0.68 0.11 180
B 1-1-2 0.77 0.68 0.11 180
C 1-1-3 0.78 0.69 0.11 180
D 1-1-3 0.58 0.51 0.11 240
E 2-1-2 0.40 0.31 0.11 180
a CAF ) 1.0 mol/L, CDF ) 3.0 mol/L, L ) 7.1 cm.
A summary of operating conditions for the different
SMBR runs is given in Table 1. In each case, the
desorbent fed to zone I was 3 mol/L diol in hexane. A
high diol concentration is desirable because it lowers
the thermodynamic activity of water that, in turn, is
more efficient for desorption. However, since the diol is
rather viscous (µ ) 2.8 cp for 3 mol/L diol in hexane at
25 °C), this concentration was used as a compromise.
Varied numbers of beds per zone, flow rates, and switch
times were used in the different runs.
Mathematical Model
As discussed above, the correct operation of an SMBR
system requires the selection of appropriate fluid-phase
velocities in the different zones. For certain idealized
conditions (e.g., linear isotherms or Langmuir iso-
therms) and in the absence of mass transfer and kinetic
effects, these operating conditions can be selected on the
basis of explicit expressions (see Lode et al.).41 In our
case, however, reaction kinetic effects and mass transfer
resistances are substantial. Moreover, the adsorption
equilibria are dependent on the thermodynamic activity
coefficients, which, in turn, vary dramatically as a
function the composition of the reactions mixture and,
thus, with conversion. A detailed mathematical model
was thus developed based on independently determined
rate expressions.
The equations used to simulate the SMBR system are
summarized in Table 2 and are based on the fixed-bed
model developed by Migliorini et al.24 Each bed is
assumed to be uniformly packed with a homogeneous
mixture of the biocatalyst (bed density Fc ) 0.32 g/cm3)
and the adsorbent (bed density Fa ) 0.16 g/cm3). The
model comprises (a) the conservation equations (eq 2.1)
for each fixed bed assuming axially dispersed plug flow;
(b) boundary conditions and mass balances to describe
the addition and removal of the fluid streams (eqs 2.2a-
f); (c) rate equations based on the LDF approximation
(eqs 2.3a-b) to describe the rates of mass transfer
between the fluid phase and the biocatalyst and between
the fluid phase and the adsorbent; (d) the rate equation
for the reaction (eqs 2.4a-b); and (d) adsorption iso-
therms describing the equilibrium distribution of sub-
strates and products between the fluid phase and the
adsorbent and between the fluid phase and the biocata-
lyst (eqs 2.5a-c). The effects of intercolumn dead
volumes were found to be negligible in our experimental
system. Thus, this volume was neglected in the mass
balances and boundary conditions connecting adjacent
columns.
The reaction kinetics is described by the reversible
Ping Pong Bi-Bi rate expression including substrate
inhibition (eq 2.4a) according to the results of Migliorini
et al.24 Since the amount of adsorbed water on Lipozyme
IM has a strong effect on the biocatalyst activity but no
effect on the substrate concentration dependence of the
rate,11 the maximum rate parameter rm in the rate
 Ind. Eng. Chem. Res., Vol. 41, No. 19, 2002 4725

Table 2. SMBR Model Equationsa

Bed conservation equations

∂ci,j ∂qi,jc ∂qi,ja ∂ci,j ∂2ci,j

 + Fc + Fa + uj ) bDL 2 + Fcvir(c,qw,ic) (2.1)
∂t ∂t ∂t ∂z ∂z
Boundary conditions and mass balances
∂ci,j
z ) 0: ujci,j0 ) ujci,j - bDL (2.2a)
∂z
∂ci,j
z ) L: )0 (2.2b)
∂z

j ) 1: cA,j0 ) cE,j0 ) cW,j0 ) 0, cD,j0 ) cDF (2.2c)

j ) 2,NI + NII: ci,j0 ) ci,j-1(L) for i ) A,D,E,W (2.2d)

QD - QE QA QD - QE
j ) NI + NII + 1: cA,j0 ) c (L) + c F, c 0 ) c (L) for i ) D,E,W (2.2e)
QD - QE + QA A,j-1 QD - QE + QA A i,j QD - QE + QA i,j-1

j ) NI + NII + 2,N: ci,j0 ) ci,j-1(L) for i ) A,D,E,W (2.2f)

Adsorption rate equations

∂qi,jc
) kic(qi,jc* - qi,jc) (2.3a)
∂t

∂qi,ja
) kia(qi,ja* - qi,ja) (2.3b)
∂t
Reaction kinetic model
rm(cA,jcD,j - cE,jcW,j/K)
r) (2.4a)
cA,jcD,j + KDmcA,j(1 + cA,j/KAi) + KAmcD,j(1 + cD,j/KDi)

rm ) rm° [0.63 - 0.35 tanh (0.66qW,jc - 3.3)] (2.4b)

Adsorption equilibria

qW,jc* ) 13.6aW,j - 19.7aW,j2 + 22.2aW,j3 (2.5a)

qW,ja* ) 56.4aW,j - 106aW,j2 + 105aW,j3 (2.5b)

qA,jc* ) 57.2aA,j/(1 + 19.7aA,j) (2.5c)

a Subscripts: A ) acid, D ) diol, E ) ester, W ) water, j ) 1,2,.....N with N ) N + N + N . Superscripts: c ) catalyst, a ) adsorbent,
I II III
F ) feed value, 0 ) bed inlet, L ) end of bed, * ) equilibrium value.

expression is a strong function of the water content of
the biocatalyst, qWc. This relationship is expressed by
an empirical function (eq 2.4.b). Accordingly, the reac-
tion rate is maximum when qWcf0, it remains nearly
constant up to qWc∼3 mmol/g, and then decreases
rapidly over the range of qWc ) 3.5 to 6.5 mmol/g to a
lower limit where the rate is only 30% of the initial
value.24 As a result, it is desirable to keep the adsorbed
water concentration on the biocatalyst at or below 3
mmol/g. This water content will be referred to as the
“deactivation limit”.
Adsorption equilibrium isotherms are used to describe
the partitioning of solutes for both the biocatalyst and
the adsorbent resin. As shown by Migliorini et al.,24 only
two of the components are significantly adsorbed: pro-
pionic acid, which is adsorbed on the biocatalyst only,
and water, which is adsorbed on both the biocatalyst
and the adsorbent resin. In both cases, the adsorption
isotherms are expressed as empirical functions of the
thermodynamic activity in the reaction mixture, which
were calculated using the UNIFAC model42 with the
parameter set of Hansen et al.43 Inclusion of activity
coefficients is necessary in this system because of the
highly nonideal nature of the reaction mixture. The
latter causes the thermodynamic activity and, hence,
the adsorption isotherm, to vary dramatically as a
function of conversion. As shown by Migliorini et al.,24
the water adsorption isotherms are S-shaped (type V)
when plotted as a function of aW. For low aW values,
water adsorption on the resin is about four times greater
than on the biocatalyst. Adsorption of propionic acid on
the biocatalyst follows a favorable type I isotherm, but
the maximum amount adsorbed is low for our experi-
mental conditions.
All of the model parameters, with the exception of the
axial dispersion coefficient, were determined by Miglior-
ini et al.24 and are summarized in Table 3. The activity
of the biocatalyst sample used in this work was lower
than that used by Migliorini et al.;24 however, the
concentration dependence and the effect of adsorbed
water were the same. As a result, the only variation is
the value of the rate coefficient r0m.
The axial dispersion coefficient, DL, was determined
as follows. First, breakthrough experiments using n-
octane as a nonadsorbed tracer in hexane were per-
4726 Ind. Eng. Chem. Res., Vol. 41, No. 19, 2002
Table 3. Model Parametersa
parameter value units
rm0 1.0 mmol/(h g)
KDm 6.5 × 10-5 mol/L
KAm 3.0 × 10-2 mol/L
KDi 5.0 mol/L
KAi 1.1 × 10-4 mol/L
K 0.6 -
kWc 7.9 h-1
kAc 3.0 h-1
kWa 1.3 h-1
Figure 3. Experimental and predicted diol profiles. Experimental
conditions: 3.0 mol/L diol, diol loading step u ) 0.13 cm/min,
hexane rinse step u ) 0.15 cm/min, L ) 7.1 cm. Lines show model
predictions with different values of Pe ) udp/bDL.
formed.23 A Peclet number Pe ) udp/bDL ) 0.3 was
found, in good agreement with the Peclet number
predicted by the correlation of Chung and Wen.44 Tracer
experiments were then done using 3 mol/L diol in
hexane. These experimental results are shown in Figure
3 along with model calculations. Although the diol is
not adsorbed, the results of positive and negative
concentration steps are quite different. In both cases,
the stoichiometric centers of the curves occur at V/Vc ∼
0.66, which coincides with the total void fraction of the
column. However, while the positive concentration step
yields a sharp curve, the negative concentration step
yields a strongly tailing curve. This difference is at-
tributable to viscous fingering. This is likely to occur
when the more viscous diol solution (µ ) 2.8 cp) is
displaced by the less viscous hexane solvent (µ ) 0.33
cp). In this case, the less viscous displacing fluid forms
“fingers” that extend into the more viscous fluid at the
rear boundary between the two fluids. These fingers
become increasingly pronounced as the displacing fluid
moves through the column, resulting in a long elution
tail. Conversely, viscous fingering is not expected to
affect the response to the positive concentration step
because, in this case, the viscosity difference actually
stabilizes the front.
As seen in Figure 3, while Pe ) 0.3 provides a good
prediction of the response to the positive concentration
step, a much lower Pe value is needed to fit the response
to the negative concentration step. It should be noted
that in describing the SMBR system, axial dispersion
and viscous fingering affect different components to a
different extent. They have the greatest effect on the
nonadsorbed species (the diol and the ester), while they
are expected to have almost no effect on the adsorbed
Figure 4. Experimental and predicted profiles for run A (1-1-1
configuration): (a) raffinate; (b) extract. Conditions are given in
Table 1.
components (water and propionic acid), for which mass
transfer resistances are dominant. Moreover, the effects
of viscous fingering are expected to be different in the
different zones of the SMBR system. Thus, to simplify
the analysis, a single Pe value was used in the model
simulations, chosen to provide the best fit of the SMBR
data. A value of Pe ) 0.06 was optimal and is interme-
diate between the two Pe values obtained in the diol
tracer experiments. This value of Pe was used in all the
simulations. More rigorous models incorporating an
explicit description of viscous fingering could be devel-
oped.45 However, it will be shown that the approximate
modeling approach used in this work produces results
in reasonable agreement with the experimental data
without occurring in the detailed description of the fluid
mechanics of viscous fingering which, as a minimum,
would require a two-dimensional transient model.
Results and Discussion
Experimental results for SMBR run A are shown in
Figure 4. The top figure shows the raffinate concentra-
tions while the bottom figure shows those for the extract
stream. This run corresponds to a 1-1-1 SMBR con-
figuration with one bed in zone I, one bed in zone II,
and one bed in zone III. Starting with initially clean
beds, the concentrations build up in the system gradu-
ally during the first few cycles. As a result of the periodic
switching of beds, a periodic steady-state is reached by

Figure 5. Experimental and predicted raffinate profiles for period
5, run A. Experimental conditions as in Figure 4.
Figure 6. Predicted adsorbed water profiles as a function of
reactor length: (a) zone I; (b) zone III. Experimental conditions of
Figure 4. Profiles are shown at the end of the period.
the fourth cycle. At this point the effluent concentrations
become periodic functions of time with a period equal
to the bed switching time. A better understanding of
the interplay of the zones and of the periodic steady-
state profiles can be obtained by plotting the raffinate
concentrations as a function of the number of column
volumes in zone III, V/Vc, rather than time. The results
for the fifth period are shown in Figure 5 on an enlarged
scale. At the start of the period, the bed that was just
moved to zone III is filled with the 3 mol/L diol feed
solution. Thus, initially, a high concentration of diol is
Ind. Eng. Chem. Res., Vol. 41, No. 19, 2002 4727
Figure 7. Experimental and predicted profiles for run B (1-1-2
configuration): (a) raffinate; (b) extract. Conditions are given in
Table 1.
seen in the raffinate. This diol is then rapidly displaced
as this bed fills with the zone III feed. As this occurs
the concentration of the ester formed in the reaction
begins to rise. As shown by Migliorini et al.,24 the acid
in zone III forms a reactive front whose speed depends
on both the reaction rate and its adsorption isotherm.
Downstream of this front no reaction takes place
because the acid is absent. Thus, initially, only a portion
of the reactor zone is active. As seen in Figure 5, the
maximum ester concentration is attained approximately
when the acid breaks through. When this occurs, acid
and diol are simultaneously present throughout the
length of the reactor zone and the maximum rate of
ester production is obtained. It can be seen that the
water concentration is kept very low in the raffinate.
When the water begins to break through, the ester
concentration begins to decline, indicating that equilib-
rium limitations have reduced the reaction rate. The
extract profiles in Figure 4b demonstrate the regenera-
tion of the adsorbent in zone I. During the first few
cycles the beds contained little water so that the water
concentration in the extract is low. By the third cycle,
water produced by the reaction in zone III begins to
appear in the extract, building up until the periodic
steady state is reached.
Predicted effluent concentration profiles are shown
in Figures 4 and 5. In general there is a good agreement
between the model predictions and the experimental
data for both the extract and raffinate. In fact, the
agreement is quite impressive when one considers that
4728 Ind. Eng. Chem. Res., Vol. 41, No. 19, 2002
Figure 8. Experimental and predicted profiles for run C (1-1-3
configuration): (a) raffinate; (b) extract. Conditions are given in
Table 1.
the thermodynamic activity coefficient of water varies
over 2 orders of magnitude in the reactor zone for these
experimental conditions. The initial acid breakthrough
is not as well predicted. Most likely this is due to slight
inaccuracies in the description of the highly favorable
acid adsorption isotherm24 and by the fact that the LDF
approximation is used to describe the rate of adsorption.
The corresponding predicted axial profiles of adsorbed
water on the biocatalyst and the adsorbent in zones I
and III are shown in Figure 6 at the end of the period
in the periodic steady state. The profiles in zone I show
that both the Dowex resin and Lipozyme are sufficiently
regenerated. The biocatalyst leaving zone I is in the fully
active state (adsorbed water less than 3 mmol/g).
Similarly, there is a very low concentration of water
adsorbed on Lipozyme in zone III as most of the water
formed in the reaction is adsorbed on the Dowex resin.
Since the biocatalyst remains below 3 mmol/g of ad-
sorbed water, full activity is maintained throughout the
period. For these conditions, the conversion attained is
limited by the rate of reaction and the reaction equi-
librium, since the simultaneous removal of water keeps
the biocatalyst away from the deactivation limit.
The effect of adding a second bed to the reaction/
adsorption zone (run B) is shown in Figure 7. The flow
rates in this 1-1-2 SMBR configuration are the same
as in run A. Thus the residence time in zone III is
doubled. The extract and raffinate concentration profiles
are qualitatively similar to the previous run. However,
Figure 9. Predicted adsorbed water profiles as a function of
reactor length; (a) zone I; (b) zone III. Experimental conditions of
Figure 8. Profiles are shown at the end of the period.
in this case a nearly complete conversion of the acid
substrate occurs, and a much higher conversion of the
diol leads to a higher purity ester product. Correspond-
ingly, a higher concentration of water is seen in the
extract (Figure 7b).
Figure 8 shows the effect of adding a third bed to the
reaction/adsorption zone. For simplicity, only the final
five cycles are shown (from 12 to 27 h). For this 1-1-3
SMBR configuration (run C), the diol substrate concen-
tration approaches small values in the raffinate stream
toward the end of the period, resulting in an even higher
ester purity. The corresponding predicted axial adsorbed
water profiles in zone III are shown in Figure 9. It can
be seen that although most of the water produced is
adsorbed on the Dowex resin, the adsorbed water
concentration on the biocatalyst has risen slightly above
the 3 mmol/g deactivation limit in the first 40% of the
first bed. This suggests that the switch time is near the
maximum because any increase, corresponding to a
decrease of the equivalent adsorbent velocity (see eq 1a),
would cause further accumulation of water and a
reduction in the catalytic activity.
The effect of increasing the switch time to 240 min
for the 1-1-3 configuration is shown in Figure 10. The
acid feed rate is the same as run C. However, the diol
feed rate and the extract flow rates are lower. Conver-
sion of the acid is, however, now far from being
complete, and a significant acid concentration breaks
through. The adsorbed water profiles are shown in
 Ind. Eng. Chem. Res., Vol. 41, No. 19, 2002 4729

Figure 10. Experimental and predicted profiles for run D (1-1-3 Figure 11. Predicted adsorbed water profiles as a function of
configuration): (a) raffinate; (b) extract. Conditions are given in reactor length: (a) zone I; (b) zone III. Experimental conditions of
Table 1. Figure 10.

Table 4. Performance Parameters

Figure 11. In this case, the adsorbed water concentra-
tion has risen above the deactivation limit over the % acid conversion % ester purity in raffinate
entire length of the first bed as well a portion of the run exp. model exp. model
second bed. The lower reaction rates caused by the A 79 85 25 31
accumulation of water, in turn, resulted in a lower B 92 93 35 40
conversion of the acid substrate. Since the diol feed rate C 93 96 43 47
was reduced for this run, a higher concentration of D 80 87 44 56
water is seen in the extract (Figure 10b). E 88 90 37 40
a
Finally, the effect of adding an additional bed to the From ref 24.
regeneration zone, zone I, is shown in Figure 12 (run
E). The addition of another bed to the desorption section As seen from these profiles, at the end of the period the
is expected to increase the desorption efficiency, allow- first bed in zone I is regenerated sufficiently so that the
ing the diol feed flow rate to be lowered while maintain- water adsorbed on the biocatalyst is below the deactiva-
ing a similar amount of regeneration. In this run, the tion limit while more than half of the water adsorbed
diol feed flow rate was reduced from 0.77 to 0.40 cm3/ on the Dowex resin has been removed.
min while keeping the switching time equal to 180 min Process Performance Parameters. In general, the
and the acid feed flow rate equal to 0.11 cm3/min. The optimization of the SMBR is dependent on the definition
experimental and predicted raffinate profiles are quite of an economic objective function. However, for simplic-
similar to those obtained in the 1-1-2 configuration ity, only the acid conversion and the ester purity in the
(see Figure 7). The extract water concentration profiles raffinate stream were used in this work to compare
are quite different, however, as in this case a much different experimental conditions. A summary of the
smaller amount of diol feed is used as a desorbent. experimental and predicted values for these two quanti-
Because essentially the same amount of water is ties is given in Table 4 for periodic steady state
produced and recovered in the extract as in run C, the conditions. The acid conversion is based on the period-
efficiency of using the desorbent has been increased average concentration in the raffinate, while the ester
substantially by the countercurrent operation with two purity is calculated from the average raffinate concen-
beds in series in zone I. The axial profiles of adsorbed trations excluding the bed void volume. These quantities
water corresponding to this run are shown in Figure can be compared directly with the corresponding equi-
13 at the end of the period in the periodic steady state. librium values for a nonseparating plug flow reactor,
4730 Ind. Eng. Chem. Res., Vol. 41, No. 19, 2002
Figure 12. Experimental and predicted profiles for run E (2-1-2
configuration): (a) raffinate; (b) extract. Conditions are given in
Table 1.
which are calculated from the following relationships:
(x*)2
K)
(1 - x*)(cFD/cFA - x*)
x*
ester purity )
1 + cFD/cFA
where x* is the equilibrium conversion of the acid. For
feed concentrations of the acid and diol substrates of 1
and 3 mol/L, we obtain x* ) 67% and an ester purity of
17%. As seen in Table 4, the SMBR runs achieved both
acid conversion and ester purity much higher than the
corresponding equilibrium values. Increasing the num-
ber of beds in zone III from one to three (runs A-C)
increases the acid conversion and the ester purity
because of the longer residence time. Increasing the
switching time from 180 to 240 min (runs C and D)
increases the average ester purity in the raffinate
because the diol concentration is reduced to a low value.
Finally, including an additional bed in zone I (run E)
yields a performance similar to that of run B, but with
greatly reduced diol consumption.
Conclusions
In this study, an enzymatic esterification has been
coupled with the adsorption of water. Previously, this
coupling has been shown to enhance the rate and
ultimate conversion in batch reactors as well as the
Figure 13. Predicted adsorbed water profiles as a function of
reactor length: (a) zone I; (b) zone III. Experimental conditions of
Figure 12.
conversion during the transient operation of fixed-bed
reactors.24 While these adsorptive reactors offered these
advantages over conventional reactors, their operation
was necessarily discontinuous. A continuous SMBR
system, integrating reaction, adsorption of water, and
regeneration, has been shown to be effective for this
reaction. The process operates in a nearly continuous
manner while overcoming equilibrium limitations and
preventing deactivation of the biocatalyst by adsorbed
water. The SMBR system offered two additional advan-
tages: reduced desorbent consumption due to maximiz-
ing the driving force for desorption through counter-
current operation, and internal recycle through zone II
of a portion of the diol used as the regenerant. A
mathematical model, based on independently deter-
mined descriptions of adsorption and reaction phenom-
ena, was developed to predict the behavior of the SMBR
system. In all cases, model predictions were in good
agreement with the experimental results obtained in
our laboratory scale system. Ester concentration profiles
were predicted well, whereas the diol concentration
profiles were predicted less accurately because of strong
tailing behavior of this species. These predictions are
impressive when one considers that they are dependent
on the simultaneous description of a number of inde-
pendent effects, including the calculation of activity
coefficients that vary as much as 2 orders of magnitude
over the conditions studied. The level of model accuracy
attained was useful as a means of directing the experi-
mental investigation and elucidating the performance-
governing parameters. The model provides a useful tool

to investigate the effects of process variables and
ultimately a powerful tool for process optimization.
Notation
ai ) thermodynamic activity of species i
ci,j ) concentration of species i in column j, mol/L
dp ) particle diameter, cm
DL ) axial dispersion coefficient, cm2/h
K ) reaction equilibrium constant
kia ) LDF adsorption rate constant for species i on the
adsorbent, 1/h
kic ) LDF adsorption rate constant for species i on the
catalyst, 1/h
Kii ) substrate inhibition constant in kinetic model, mol/L
Kim ) Michealis-Menten constant in kinetic model, mol/L
L ) bed length, cm
Nj ) number of beds in zone j
p ) switching time, h
Pe ) Peclet number ( ) udp/bDL)
Qj ) fluid flow rate in zone j for j ) I, II, or III or fluid flow
rate of acid feed, diol feed, and extract for j ) A, D, and
E, respectively, cm3/min
qi,ja ) adsorbed concentration of species i in adsorbent
particles, mmol/g
qi,jc ) adsorbed concentration of species i in the catalyst,
mmol/g
r ) reaction rate, mmol/g
rm ) reaction rate coefficient in kinetic model, mmol/(g h)
t ) time, h
u ) fluid velocity, cm/h
uj ) fluid velocity in column j, cm/h
j i ) true countercurrent equivalent fluid velocity in column
u (15) Van der Padt, A.; Sewalt J. J.; Van’t Riet, K. On-line water
i of a SMBR, cm/h
j s ) true countercurrent equivalent solid velocity in column
u
i of a SMBR, cm/h
V ) effluent volume, cm3
Vc ) column volume, cm3
x* ) equilibrium conversion of limiting reactant
z ) axial coordinate measured from entrance to zone, cm
Greek Symbols
 ) total void fraction
b ) bed extraparticle void fraction
p ) particle porosity
νi ) stoichiometric coefficient of species i
Fa ) mass of adsorbent per unit column volume, g/cm3
Fc ) mass of catalyst per unit column volume, g/cm3
Acknowledgment
This research was supported in part by NSF grants
BCS-9301447 and GER-9452654. We thank Dr. Gio-
vanni Biressi for his help in developing the SMBR
simulation code.
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Received for review April 5, 2002
Revised manuscript received July 17, 2002
Accepted July 24, 2002
IE0202625