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Modeling and Scale-up of Sitosterol Hydrogenation Process: From LaboratorySlurry Reactor to Plant Scale
Johan Wa1rnå,† Manuel Flores Geant,† Tapio Salmi,† Antti Hamunen,‡ Juha Orte,‡Rami Hartonen,‡ and Dmitry Yu. Murzin* ,†
Laboratory of Industrial Chemistry, Åbo Akademi UniVersity, Biskopsgatan 8, 20500 Åbo/Turku, Finland, andRaisio Life Sciences, Raisionkaari 60, PL 101, 21201 Raisio, Finland
The hydrogenation kinetics of an industrially relevant mixture of sterols was studied over a commercialpalladium catalyst in a laboratory reactor. The experimental data was used to estimate the kinetic parametersfor the proposed reaction network. The kinetic parameters estimated from experimental data described verywell the concentrations of the stanol and sterol compounds. These parameters were used to simulate theindustrial reactor, calculating the gas-liquid mass-transfer coefficients of hydrogen. The simulation of theplant-scale reactor, which was based on the kinetic parameters estimated from laboratory data, was successfulfor the description of the main products and reactants.
1. Introduction
Cholesterol is found in almost all tissues of animals,particularly in the brain, in the spinal column, and in gallstones.1
A high level of cholesterol is a leading risk factor for heartdiseases. Since cardiovascular diseases are one of the leadingcauses of death, the development of functional food to enhancethe cholesterol-lowering ability of traditional food products isincreasing. Although it has been known as early as the 1950sthat phytosterols and phytostanols can lower blood cholesterol,2a,2b
cholesterol-lowering margarines containing plant stanol esterhave recently made a breakthrough into the American andEuropean markets.3a In Finland, commercial production of thesemargarines started in 1995.3a
Phytosterols have a role in plants similar to that of cholesterolin mammals, e.g., they are forming cell membrane structures.More than 40 sterols have been identified, of whichâ-sitosterol,campesterol, and stigmasterol are the most abundant. Thesephytosterols and cholesterol share identical ring structures,belonging to the class of 4-desmethylsterols.4a
A less-abundant class of related compounds found in plantsis the phytostanols. Phytostanols are completely saturated formsof plant sterols and lack the carbon-carbon double bond foundin cholesterol and phytosterols. Figure 1 compares the structureof cholesterol, phytosterols, and phytostanols.
The consumption of phytosterols and phytostanols lowersblood cholesterol levels by inhibiting the adsorption of dietaryand endogenously produced cholesterol from the small intestine,and the phytosterols/phytostanols are only very poorly adsorbedthemselves.
Although both phytosterols and phytostanols present choles-terol-lowering properties, the superior ability of phytostanols toinhibit cholesterol absorption is known. This difference is alsoattributed to small structural differences: the longer the sidechain attached to the sterol molecule and the fewer double bondsthere are, the less sterol/stanol is adsorbed. This knowledge isthe main reason for application of stanols and the driving forcefor further improvement of the production process of stanols,specifically the phytosterols catalytic hydrogenation. The follow-
ing step in the commercial process is esterification leading toplant stanol ester.3b Numerous clinical studies have shown thatplant stanol ester reduces serum total cholesterol by 10%, theharmful low-density lipoprotein (LDL) cholesterol by 10-15%,and also the levels of plant sterols by 30-50% in both short-and long-term studies when consumed regularly.3 The currentunderstanding of the role of plant stanol esters is that first theyreduce the incorporation of cholesterol and plant sterols into themicelles.4c,d Consequently, this reduces cholesterol absorptioninto the enterocytes. In the second step, plant stanol ester increas-es the ABC A1-mediated efflux of cholesterol within the enter-ocyte and pumps the cholesterol back into the intestinal lumen.4e
The present work is devoted to kinetics modeling of plantsterols hydrogenation as well as modeling of an industrialreactor. The generated knowledge is essential in furtherimprovement of this process on an industrial scale. Recently, akinetic modeling study9 of hydrogenation of plant sterols usingpolymer fiber-supported Pd catalyst was published. This studydid not include the formation of byproducts and was also limitedto one pressure and a rather narrow temperature interval.
2. Experimental Section
2.a. Raw Materials. The raw material, i.e., the reactantmolecules, used in this work is derived from vegetable oilprocessing or wood pulping processes. In addition toâ-sitosterol(ca. 45-47%) (MW ) 414.7 g/mol), the feed sterol containsother sterol species, the most frequent of which are campesterol(ca. 25%), stigmasterol (ca. 18%), brassicasterol (ca. 2%), andthe target product, sitostanol itself (ca. 2-4%). The sterol feedhas a melting point of 135°C.
2.b. Reaction Network.Generally speaking, hydrogenationof plant sterols yields the respective stanols by hydrogenatingthe carbon-carbon double bond and the CdO bond. Somebyproducts can be formed during the hydrogenation, primarythe ketone and the unsaturated compounds. A proposed routefor the hydrogenation of sitosterol and campesterol is sketchedin Figure 2. The molecular structures of the main reactants areshown in Figure 1.
In general, it is possible to identify 12 compounds in the reac-tion scheme. However, in the present work, the campesterol iso-mer species was not taken into account, since it did not appearin the analysis of the samples. This implies that, in total, 11compounds were analyzed.
* Corresponding author. E-mail: [email protected].† Åbo Akademi University.‡ Raisio Life Sciences.
7067Ind. Eng. Chem. Res.2006,45, 7067-7076
10.1021/ie0514298 CCC: $33.50 © 2006 American Chemical SocietyPublished on Web 09/20/2006
2.c. Hydrogenation Procedure.Sitosterol and campesterolwere hydrogenated to sitostanol and campestanol in a batchreactor over 5% Pd catalysts on active Carbon Degussa (catalyst1 with the specific surface area)1010 m2/g, and catalyst 2 withthe surface area) 800 m2/g, Degussa) in an organic solvent(2-propanol). The reactor volume was 1000 mL, and the liquidvolume in the reactor was 500 mL.
A mixture of plant sterols (sitosterol, campesterol, stigmas-terol, and brassicasterol) was used as a raw material. Eighteenexperiments were performed under different conditions, varyingthe temperature (70-120°C) and hydrogen pressure (4-45 bar)over a Pd catalyst. The experimental conditions are listed inTable 1. The batch reactor was equipped with a heating jacketable to keep the temperature of the reaction fluid constant.
The reactor was also equipped with four valves. The hydrogenand nitrogen valves were used, respectively, to open/close thehydrogen or nitrogen feed. The vacuum valve was employedto extract undesired gases from the system and reduce thepressure within it, while the sampling valve was used to takesamples. The reactor also had a stirrer system with an efficientimpeller, a digital thermometer, a manometer, and a hydrogenflowmeter.
The reactant mixture was prepared by dissolving 133 g ofraw material (plant sterols) into 422 g of solvent (1-propanol,99.99% purity). The solution was poured in the batch reactortogether with the catalyst. The amount of catalyst was 2.9 g inexperiments 1-10 and 1.25 g in experiments 11-18. The
Figure 1. Structures of cholesterol and common phytosterols and phytostanols.
Figure 2. Reaction scheme for hydrogenation of sterols.
Table 1. Experimental Conditions: Catalyst 1 Was Used inExperiments 1-9 (2.9 g) and Catalyst 2 (1.25 g) Was Used inExperiments 10-18
exp. no.pressure
(bar)temp(°C) exp. no.
pressure(bar)
temp(°C)
1 4 70 10 30 952 4 120 11 45 1203 4 95 12 45 954 7 70 13 30 955 7 95 14 30 706 7 120 15 45 707 9.5 120 16 15 1208 9 95 17 30 1209 9 70 18 15 70
7068 Ind. Eng. Chem. Res., Vol. 45, No. 21, 2006
reactor was closed, and immediately, the oxygen from the airwas removed from the system by adding nitrogen and thenpurging it using the vacuum line. Once the system, filled withthe sterols solution and the catalyst, was oxygen-free, the heatingand stirring were started and kept until the system reached thesteady state. The stirring speed was 1000 rpm in all experiments.It was verified that experiments were conducted in the kineticregime, free from the influence of external and internal diffusion.Some initial hydrogenation experiments were performed withstirring speeds from 700-1500 rpm. These tests showed that astirring speed of 1000 rpm is sufficient for the reactor to operatein the kinetic regime.
When the system reached the steady state (temperature), thereaction was commenced by opening the hydrogen valve. Thesteady state was set at the time when the temperature insidethe reactor was stabilized. Temperature inside the reactorincreased just after the reaction was commenced, and then itstabilized again after a short time (∼3 min, depending primarilyon the experiment temperature and the mass of catalyst).
Samples were taken along the reaction, and at the same time,temperature and pressure were registered. Hydrogen flow ratewas also registered during the experiments. The samplinginterval depended on the length of the experiment; samples werewithdrawn at 5-15 min intervals and thereafter with a longerinterval. The sample flasks were filled by opening the samplingvalve, and the stirring speed was decreased to 400 rpm to takethe sample. Sample flasks were weighed before and after thesamples were taken for further analysis by GC (Hewlett-Packard6890 with HP 5 column: 30 m/0.32 mm i.d./o.s. 5µm df, flameionization detector (FID) at 300°C).
Part of the catalyst initially poured in the batch reactor leftthe system when the samples were taken. To know howsignificant the loss of catalyst was, the following calculationswere done.
The distribution of catalyst in the system was assumed to beuniform, which implies that the catalyst concentration in thesystem does not vary between different locations. The catalystconcentration was calculated using the following equation:
Figure 3. (a) Fit of the model to experimental data, wt % as a function oftime (min) (catalyst 1): plus sign, sitosterol; open circle, campesterol; right-facing triangle, stigmasterol; left-facing triangle, brassicasterol; asterisk,sitostanol;×, campestanol. (b) Fit of the model to experimental data, wt%as a function of time (min) (catalyst 1): plus sign, sitosterol; open circle,campesterol; right-facing triangle, stigmasterol; left-facing triangle, bras-sicasterol; asterisk, sitostanol;×, campestanol.
Figure 4. (a) Fit of the model to experimental data, wt % as a function oftime (min) (catalyst 2): plus sign, sitosterol; open circle, campesterol; right-facing triangle, stigmasterol; left-facing triangle, brassicasterol; asterisk,sitostanol;×, campestanol. (b) Fit of the model to experimental data, wt %as a function of time (min) (catalyst 2): plus sign, sitosterol; open circle,campesterol; right-facing triangle, stigmasterol; left-facing triangle, bras-sicasterol; asterisk, sitostanol;×, campestanol.
Ind. Eng. Chem. Res., Vol. 45, No. 21, 20067069
All the sample flasks were weighed before and after the sampleswere taken; therefore, the mass of sample was determined asthe difference of these two values:
It is possible to estimate the mass of catalyst taken out withevery single sample, if the concentration of catalyst in the systemand the mass of the sample are known:
The amount of catalyst that leaves the system is proportionalto the number of samples taken and the mass of sample.
Experimental results demonstrated that 97% of the initialamount of catalyst remained in the system. This value provedthat the catalyst losses do not represent a considerable problem,and for the calculations, the amount of catalyst was assumed tobe invariable.
3. Results
Typical kinetic curves are given in parts a and b of Figures3 (catalyst 1) and 4 (catalyst 2) for the main components. Thewhole set of both catalysts’ experimental data, also includingbyproducts, is provided in the Supporting Information. Thereaction rate was essentially the same, independent of hydrogenpressure. As expected, increased temperature resulted in higherreaction rates; see Figure 5. Figure 6 shows the sterol concentra-tion with time at 95°C and different hydrogen pressures.
The influence of the vapor pressure of the solvent (1-propanol) had to be taken into account in the calculations, sinceit lowers the hydrogen partial pressure in the reactor. The vaporpressure can be obtained from the Clausius-Clapeyron equa-tion5
where Hvap is 47 200 J/mol for propanol and the referencetemperature and pressure areT1 ) 371.15 K andP1 ) 1 bar,respectively;R is the gas constant.
In the kinetics and reactor modeling, the recorded totalpressure in the reactor was corrected by subtracting the vaporpressure of 1-propanol, in order to get the hydrogen pressure.
Solubility of hydrogen in 1-propanol (x* ) 0.000 234) and2-propanol (x* ) 0.000 266) at 1 bar and 298.2 K was reported.6
The solubility of hydrogen in sitosterol/1-propanol solution hasbeen previously measured.7 The results are summarized in Table2.
4. Modeling
4.a. Kinetic Model. The kinetic model was based on thefollowing hypothesis: molecularly adsorbed hydrogen wasassumed to react on the catalyst surface with adsorbed organicspecies. The role of hydrogen in catalytic hydrogenation wasdebated in the literature. Taking into account the fact that theimpact of hydrogen pressure on reaction rate is negligible andthe fact that smaller-in-size adsorbed hydrogen does not competefor sites with the much-larger molecules adsorbed on the surface,the adsorption of hydrogen and organic components waspresumed to be noncompetitive. Keeping in mind that it is closeto zero order in hydrogen, an alternative explanation ofcompetitive hydrogen adsorption would result in a kineticequation for sitosterol hydrogenation with only first-orderdependence in sterols. Since this model was qualitatively indisagreement with the experimental data, it was disregarded.Preliminary analysis of the reaction rate dependence on hydro-gen concentration revealed that discrimination between molec-ular and dissociative hydrogen adsorption cannot be performedin a meaningful way; therefore, molecular hydrogen adsorptionwas preferred, because in principle, it gives a possibility todescribe first order in hydrogen frequently observed in hydro-genation of carbon-carbon double bonds.
The surface hydrogenation step was assumed to be ratelimiting, whereas the adsorption and desorption steps wereregarded as rapid quasi-equilibria.
Equilibrium for hydrogen adsorption gives
resulting in
Analogously, the following is obtained for adsorption of A
From the balance equation
equilibrium constants could be obtained, finally leading to
Figure 5. Influence of temperature on reaction rate (4 bar).
wcat ≈m0,cat
m0,cat+ m0,1-propanol+ m0,sterols(1)
msample) mflask+sample- mflask (2)
mcat-out ) msamplewcat (3)
ln(P1
P2) )
Hvap
R ( 1T1
- 1T2
) (4)
PH2) Ptot - x1-propanolP1-propanol
vap (5)
H2 + *’ h H2*’ (6)
A + * h A* (7)
KH2)
θH2
/
cH2θ′0
θ′H2) KH2
cH2θ′0 θ′H2
+ θ′0 ) 1
(8)
θ′H2)
KH2cH2
1 + KH2cH2
(9)
θA* ) KAcAθ0 (10)
1 ) θ0 + θA + θB + θC + θD + θE + θF +θG + θI + θJ + θK (11)
7070 Ind. Eng. Chem. Res., Vol. 45, No. 21, 2006
where indexi denotes the components (A) sitosterol, B)sitostanol, C) sitostanone, D) sitostane, E) campesterol, F) campestanol, G) campestanone, H) campestane, I)brassicasterol, J) stigmasterol, and K) sitosterol isomer) andindex j denotes the reactions (1-16; see Figure 2).
On the basis of this mechanistic hypothesis, the rates of thehydrogenation steps become
whereD andDH2 are defined as
As mentioned above, campesterol isomer (Figure 2) was notdetected in the analysis of the samples; therefore, it is notincluded in the kinetic model.
The influence of temperature on the rate and adsorptioncoefficients can be accounted for with the Arrhenius and vanHoff equations.
The rate constants (k0,j), adsorption constants (K0,i), activationenergies (∆EA), and adsorption enthalpies were estimated fromthe laboratory experiment data by nonlinear regression.
4.b. Reactor Model. The mass balance for a liquid-phasecomponent (i) in a batch reactor was written as
whereri is the reaction rate andFB is the catalyst bulk density(FB ) mcat/Vliq). The mass balance eq 17 is valid in the kineticregime, i.e., in the absence of mass-transfer limitations.
Hydrogen is present both in the gas and liquid phases; thus,the mass balance is written as
where the fluxNHav between the gas and liquid phase is
The gas-liquid equilibrium constantK is obtained from gas-liquid solubility data.
wherex* is the saturation molar fraction of the gas componentin the liquid phase. The laboratory reactor was well-stirred,which ensures that the gas-liquid mass-transfer rate (kla) didnot influence the reaction rate.
4.c. Parameter Estimation.The proposed kinetic model andthe equations of the batch reactor were linked to the MODESTsoftware;8 the code was compiled and used for the parameterestimation of the data obtained in the experimental work. Therate constants, adsorption coefficients, heats of adsorption, andactivation energies included in the kinetic model were estimatedfrom the laboratory experiments by nonlinear regression withthe Levenberg-Marquardt method. The reactor mass balances
rj )k′jKAKH2
cjcH2
(1 + ∑Kici)(1 + KH2cH2
)(12)
r1 )k1KAKH2
cAcH2
DH2D
r2 )k2KAcA
D
r3 )k3KAKH2
cAcH2
DH2D
r4 )k4KJKH2
cJcH2
DH2D
r5 )k5KCKH2
cCcH2
DH2D
r6 )k6KJKH2
cJcH2
DH2D
r7 )k7KAKH2
cAcH2
DH2D
r8 )k8KKKH2
cKcH2
DH2D
(13)
r9 )k9KEKH2
cEcH2
DH2D
r10 )k10KEcE
D
r11 )k11KEKH2
cEcH2
DH2D
r12 )k12KIKH2
cIcH2
DH2D
r13 )k13KGKH2
cGcH2
DH2D
r14 )k14KIKH2
cIcH2
DH2D
D ) 1 + KAcA + KBcB + KCcC + KDcD + KEcE + KFcF +KGcG + KIcI + KJcJ + KKcK (14)
DH2) 1 + KH2
cH2(15)
kj ) k0,j e-∆EAj/R(1/T-1/Tmean)
Ki ) K0,i e∆H/R(1/T-1/Tmean) (16)
dci
dt) FBri (17)
dcH
dt) NHav + rHFB (18)
NHav ) klav(PG/RT
K- cH) (19)
K )cG
x*ctot(20)
Ind. Eng. Chem. Res., Vol. 45, No. 21, 20067071
were solved as a subtask to the parameter estimation with thebackward difference method. The parameter estimation routineminimizes the objective function, the sum of square error (Q),which is defined as
where yexp is the component concentration obtained fromexperiments,yest is the component concentration predicted bythe model, andw is the weight factor for the experimental point.The weight factor was set to 1 for all experimental points.
The parameter estimation was performed by applying the esti-mation procedure directly to the data. The program was executed
many times; it has the built-in option to use the last result as astarting condition for the next estimation. Different sets of initialvalues for the calculation of the model parameters were alsotried, finally permitting the convergence of the numericalprocedure.
The number of components and reactions in the estimationwere 11 and 14, respectively, giving 14 rate constants, 14activation energies, 12 adsorption coefficients, and 12 adsorptionenergies, altogether 52 adjustable parameters. Some initialparameter estimations with all 52 parameters revealed that thereare too many parameters, resulting in large parameter errors.To reduce the number of parameters, some assumptions weremade; in particular due to the small temperature difference (∆T) 50 °C) in the experiments, the possible variations for heat ofadsorption of hydrogen with temperature were neglected.Furthermore, the adsorption coefficients for sitosterol-campes-terol, sitostanol-campestanol, sitonanone-campestanone, si-tostane-campestane, and stigmasterol-brassicasterol were setequal to each other, which is a reasonable assumption takinginto account their structural similarities. With these modifica-tions, the number of parameters was reduced to 36.
To reduce further the number of parameters, some assump-tions were made after initial estimations with all parameters.The reaction rates for reactions 5 and 13 were very low.Therefore, these reactions were considered to be nonsignificant.For reactions 4 and 12 to occur, two double bonds should be
Figure 6. Influence of pressure, 4, 7, and 9 bar at 95°C (left) and 15, 30, and 45 bar at 120°C (right).
Table 2. Solubility of Hydrogen in Sitosterol/Propanol Solution
temperature (°C) pressure (bar) wt % sitosterol x*H2
65 10 1075 10 10 0.0037490 10 10 0.00385
110 10 10 0.0042975 5 10 0.0013190 5 10 0.00138
110 5 10 0.00147
Table 3. Parameter Estimation Results (TMean)100°C)
experiments 1-9catalyst 1
explained 99.82%
experiment 10-18catalyst 2
explained 99.06%
parametervalue
std.error (%)
parametervalue
std.error (%)
k1 (mol/(m3 min)) 274 13.9 548 34.1k2 (mol/(m3 min)) 7.51 14.2 25.2 28.7k3 (mol/(m3 min)) 1.93 17.3 57.1 23.9k6 (mol/(m3 min)) 15.5 5.8 421 21.2k7 (mol/(m3 min)) 2.95 19 1470 30.6k8 (mol/(m3 min)) 0.0109 53.1 5.37 19.2k9 (mol/(m3 min)) 259 13.9 1660 18.9k10 (mol/(m3 min)) 12.2 15.1 39.9 26.8k11 (mol/(m3 min)) 0.761 27.7 0.0607 68.5k14 (mol/(m3 min)) 44.4 24.8 2 970 34.4∆EA1 (J/mol) 57 000 2.8 74 100 5.2∆EA2 (J/mol) 95 300 3.4 55 200 20.9∆EA3 (J/mol) 124 000 3.8 98 000 9.5∆EA6 (J/mol) 43 700 4.8 80 100 6.1∆EA7 (J/mol) 99 900 10 84 400 5.3∆EA8 (J/mol) 27 500 36.3 41 200 5.7KA (m3/mol) 0.000 776 19.6 0.001 61 29KB (m3/mol) 0.718 20.1 6.51 26.2KJ (m3/mol) 0.018 6 12.5 0.014 7 26.1KK (m3/mol) 0.061 8 38.2 4.87 21KH2 (m3/mol) 0.275 11.1 0.056 2 15.1∆H2 (J/mol) 18 600 25.2 3 440 58.3
Q ) ∑(yexp - yest)2w (21)
Figure 7. Fit of the model to experimental data, wt % as a function oftime (min), byproducts (catalyst 2):g, stigmasterol isomer;3, sitostanone;0, campestanone.
7072 Ind. Eng. Chem. Res., Vol. 45, No. 21, 2006
hydrogenated simultaneously. In further calculations, they wereomitted. The activation energies for the pairs of similar sterols(i.e., sitosterol-campesterol) were set equal to each other (EA9
) EA1, EA10 ) EA2, EA11 ) EA3, EA12 ) EA4, EA13 ) EA5) alsodue to structural similarities. The number of kinetic parametersto estimate was now 22.
The results of the fitting are shown in Table 3. The highestdegree of explanation (R2) defined as
was 99.8%.The kinetic model described very well the concentrations of
the reactants and the main products, stanols and sterols; seeparts a and b of Figures 3 and 4 and the figures in the SupportingInformation. However, the fit of the kinetic model for the byprod-ucts, stanes and stanones, as exemplified in Figure 7, was notas good as for the main products. This was mainly due to themuch lower concentrations of byproducts (stanes and stenes).
Parts a and b of Figures 8 and 9 show parity plots forexperimental and estimated concentrations for the sterols, stanol,
stane, and stanone. It is clearly noticed from part a of Figures8 and 9 that the stanol and sterol behavior is very well-describedwithin the range of temperature and hydrogen pressure used inthe experimental work. Because of the rather narrow temperatureinterval, the analysis of parameter significance should beperformed with care; the value of activation energy for the mainreaction, hydrogenation of sitosterol to sitostanol, is, however,very similar to the one reported in the literature for Pd fibercatalyst, e.g., ca. 50 kJ/mol.9
The correlation matrixes for the estimated parameters areshown in Tables 4 and 5, and the sensitivity plots for allestimated parameters are displayed in Figure 10.
4.d. Plant-Scale Reactor.The developed kinetic model wasused to predict the plant-size reactor behavior. A characteristicfeature for a plant-size reactor is the presence of hydrogen mass-transfer resistance. In the simulations, only the gas-liquid mass-transfer coefficients were fitted.
Experimental data were collected from a plant reactor of 8m3 with 25 kg of catalyst. The plant reactor was simulated withthe values of kinetic parameters obtained from the laboratoryreactor (see previous section). The simulation of the plant reactorgave the values of the gas-liquid mass-transfer coefficient (kla)equal to 0.34 min-1. For efficiently stirred tank reactors, the
Figure 8. (a) Fit of the model to experimental data (catalyst 1): reactantsand main productsssitostanol and campestanol (catalyst 1). (b) Fit of themodel to experimental data (catalyst 1): byproductssstigmasterol isomer,sitostanone, campestanone, sitostane, and campestane (catalyst 1).
R2 ) 100(1 -(|yexp - yest|)2
(|yexp - yjexp|)2) (22)
Figure 9. (a) Fit of model to experimental data: reactants and mainproductsssitostanol and campestanol (catalyst 2). (b) Fit of model toexperimental data: byproductssstigmasterol isomer, sitostanone, campes-tanone, sitostane, and campestane (catalyst 2).
Ind. Eng. Chem. Res., Vol. 45, No. 21, 20067073
typical values are ca. 3-12 min-1,10 demonstrating the lowefficiency of gas/liquid mass transfer in the plant reactor.
Results displayed in Figure 11 demonstrate the successfulapplication of the adopted approach in process scale-up. Themodel can predict the formation of the main products very well(Figure 11).
Figure 12 shows the calculated concentration of hydrogen inthe reaction mixture in the plant conditions. During the first100 min, the hydrogen concentration is very low because all
Figure 10. Sensitivity plots for the estimated parameters (catalyst 1).
Figure 11. Simulation of a plant reactor, 4 bar and 70°C, based onlaboratory data.O indicates experimental points from the plant reactor, andlines indicate simulated data.
Tab
le4.
Cor
rela
tion
Mat
rixfo
rth
eE
stim
ated
Kin
etic
Par
amet
ers,
Exp
erim
ents
1-9
(Cat
alys
t1)
k 11.
00k 2
0.93
1.00
k 30.
690.
571.
00k 6
0.01
0.02
-0.
121.
00k 7
0.65
0.55
0.37
-0.
131.
00k 8
0.03
0.07
0.09
-0.
21-
0.02
1.00
k 90.
990.
930.
680.
030.
650.
031.
00k 1
00.
870.
870.
56-
0.04
0.54
0.10
0.88
1.00
k 11
0.16
0.13
0.27
0.11
0.12
-0.
340.
160.
021.
00k 1
40.
050.
050.
16-
0.30
-0.
06-
0.05
0.02
0.05
-0.
091.
00∆
EA
1-
0.15
-0.
180.
01-
0.04
-0.
20-
0.03
-0.
16-
0.17
0.01
-0.
121.
00∆
EA
2-
0.01
-0.
240.
09-
0.04
0.11
-0.
09-
0.01
-0.
210.
030.
020.
381.
00∆
EA
30.
020.
12-
0.38
0.07
0.07
-0.
070.
030.
10-
0.21
-0.
230.
12-
0.19
1.00
∆E
A6
-0.
12-
0.14
0.07
0.20
-0.
160.
00-
0.12
-0.
13-
0.03
0.03
0.48
0.19
-0.
071.
00∆
EA
70.
060.
110.
090.
19-
0.53
0.10
0.06
0.10
-0.
010.
090.
23-
0.18
-0.
110.
161.
00∆
EA
80.
160.
140.
31-
0.35
0.24
0.67
0.16
0.19
-0.
140.
17-
0.08
-0.
05-
0.14
-0.
03-
0.09
1.00
KA
-0.
85-
0.87
-0.
42-
0.12
-0.
52-
0.01
-0.
85-
0.80
-0.
110.
030.
440.
26-
0.28
0.35
-0.
07-
0.06
1.00
KB
-0.
12-
0.20
-0.
130.
03-
0.02
0.02
-0.
13-
0.17
-0.
220.
130.
540.
48-
0.33
0.46
0.01
-0.
100.
511.
00K
J-
0.22
-0.
320.
19-
0.47
0.00
0.12
-0.
23-
0.25
-0.
040.
260.
450.
38-
0.49
0.47
-0.
150.
270.
640.
651.
00K
K0.
030.
110.
06-
0.30
-0.
040.
110.
020.
10-
0.03
-0.
050.
18-
0.12
0.24
0.12
0.13
0.40
-0.
06-
0.24
0.07
1.00
KH
2-
0.22
-0.
05-
0.28
-0.
21-
0.11
0.14
-0.
22-
0.08
-0.
040.
09-
0.07
-0.
140.
36-
0.05
-0.
050.
04-
0.06
-0.
32-
0.23
0.49
1.00
∆H
20.
00-
0.03
-0.
030.
120.
13-
0.02
0.00
-0.
040.
060.
27-
0.56
0.07
-0.
36-
0.36
-0.
24-
0.11
0.00
0.14
-0.
03-
0.48
-0.
061.
00k 1
k 2k 3
k 6k 7
k 8k 9
k 10
k 11
k 14
∆E
A1
∆E
A2
∆E
A3
∆E
A6
∆E
A7
∆E
A8
KA
KB
KJ
KK
KH
2∆
H2
7074 Ind. Eng. Chem. Res., Vol. 45, No. 21, 2006
hydrogen in the liquid phase is immediately consumed by thereaction, and thus, the gas-liquid mass-transfer rate controlsthe overall reaction rate. After 100 min of reaction, lesshydrogen is consumed and the hydrogen concentration ap-proaches the saturation level determined by the gas-liquidequilibrium constant.
5. Conclusions
Hydrogenation of an industrially relevant mixture of sterolscomprising sitosterol, campesterol, stigmasterol, and brassicaster-ol was carried out over a commercial palladium catalyst at hydro-gen pressures of 4-45 bar and temperatures of 70-120 °C.
The reaction rate was found to be independent of the hydrogenpressure. The apparent activation energy was found to be 57kJ/mol.
The experimental data was used to estimate the kinetic param-eters for the proposed reaction network. The estimated param-eters described very well the concentrations of the stanol andsterol compounds.
The estimated parameters from laboratory experiments wereused to simulate the industrial reactor. For these calculations,the gas-liquid mass-transfer coefficients of hydrogen werecalculated. The simulation of the plant-scale reactor wassuccessful for the description of the main products and reactants.
Acknowledgment
This work is part of the activities at the Åbo Akademi ProcessChemistry Centre (PCC) within the Finnish Centre of ExcellenceProgram (2000-2011) by the Academy of Finland.
Supporting Information Available: Supporting Informationcontains experimental data and fits of the model for the reactants,main products, and byproducts for both catalysts as well assensitivity plots. This material is available free of charge viathe Internet at http://pubs.acs.org.
Notation
av ) mass-transfer area/reactor volume (m2/m3)c ) concentration (mol/m3)∆EA ) activation energy (J/mol)∆H ) adsorption enthalpy (J/mol)k ) rate constant (min-1)kl ) gas-liquid mass-transfer coefficient (m/s)K ) gas-liquid equilibrium constantKA-K ) adsorption coefficient, (m3/mol)mcat ) mass of catalyst (kg)NH ) flux of hydrogen from gas to liquid (mol/(m3 s))T
able
5.C
orre
latio
nM
atrix
for
the
Est
imat
edK
inet
icP
aram
eter
s,E
xper
imen
ts10
-18
(Cat
alys
t2)
k 11.
00k 2
-0.
051.
00k 3
-0.
190.
131.
00k 6
-0.
330.
140.
141.
00k 7
-0.
540.
420.
730.
311.
00k 8
-0.
850.
240.
520.
360.
871.
00k 9
-0.
160.
470.
760.
200.
900.
601.
00k 1
0-
0.29
0.33
0.17
0.02
0.39
0.34
0.32
1.00
k 11
0.47
0.22
0.20
-0.
140.
01-
0.28
0.24
0.22
1.00
k 14
0.10
-0.
070.
200.
080.
110.
030.
160.
390.
571.
00∆
EA
1-
0.04
0.00
-0.
06-
0.06
0.06
0.09
0.07
0.04
-0.
020.
041.
00∆
EA
20.
050.
33-
0.30
-0.
02-
0.20
-0.
15-
0.20
0.11
0.11
-0.
210.
081.
00∆
EA
3-
0.10
0.02
0.00
0.16
0.15
0.19
0.12
0.07
-0.
170.
010.
830.
001.
00∆
EA
6-
0.10
-0.
03-
0.05
-0.
050.
050.
110.
010.
03-
0.04
0.05
0.76
0.12
0.72
1.00
∆E
A7
0.39
-0.
06-
0.22
-0.
23-
0.29
-0.
35-
0.18
-0.
150.
06-
0.02
0.75
0.15
0.73
0.65
1.00
∆E
A8
0.56
-0.
14-
0.26
-0.
04-
0.45
-0.
55-
0.29
-0.
210.
140.
03-
0.17
-0.
080.
17-
0.04
0.28
1.00
KA
-0.
21-
0.33
-0.
450.
10-
0.49
-0.
18-
0.67
0.00
-0.
56-
0.27
-0.
080.
130.
00-
0.05
-0.
030.
081.
00K
B-
0.31
0.24
-0.
200.
390.
230.
340.
120.
30-
0.45
-0.
230.
100.
050.
320.
06-
0.04
-0.
010.
461.
00K
J-
0.10
-0.
12-
0.05
-0.
55-
0.13
-0.
03-
0.20
0.21
-0.
35-
0.25
-0.
010.
01-
0.04
0.11
0.03
-0.
080.
560.
291.
00K
K-
0.26
-0.
06-
0.05
0.22
-0.
060.
07-
0.18
0.23
-0.
49-
0.24
-0.
040.
050.
09-
0.07
-0.
06-
0.05
0.80
0.62
0.58
1.00
KH
20.
080.
07-
0.16
-0.
03-
0.17
-0.
29-
0.16
0.12
0.13
-0.
200.
030.
090.
010.
030.
080.
150.
090.
010.
010.
121.
00∆
H2
-0.
03-
0.11
-0.
080.
23-
0.08
-0.
03-
0.11
-0.
210.
030.
14-
0.14
-0.
11-
0.07
-0.
10-
0.15
-0.
09-
0.08
-0.
22-
0.35
-0.
22-
0.07
1.00
k 1k 2
k 3k 6
k 7k 8
k 9k 1
0k 1
1k 1
4∆
EA
1∆
EA
2∆
EA
3∆
EA
6∆
EA
7∆
EA
8K
AK
BK
JK
KK
H2
∆H
2
Figure 12. Simulation of plant reactor: concentration of hydrogen (mol/m3) in the liquid phase as a function of time (min).
Ind. Eng. Chem. Res., Vol. 45, No. 21, 20067075
P ) pressureQ ) sum of squaresr ) reaction rate (mol/(m3 s))R ) gas constant (8.31 J/(mol K))R2 ) degree of explanationt ) time (min)T ) temperature (K)Tmean) mean temperature of experiments (K)Vliq ) liquid volume (m3)w ) weight factorwcat ) catalyst fractionyexp ) experimental valueyest ) estimated valueFB ) catalyst bulk density) mcat/Vliq
Component Symbols and Legends in Figures
A ) sitosterol,0B ) sitostanol,]C ) sitostanone,3D ) sitostane,∆E ) campesterol, oF ) campestanol,×G ) campestanone,+H ) campestane, *I ) brassicasterol,<J ) stigmasterol,>K ) sitosterol isomer,f
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(3) (a) IFST: Current Hot Topics, Phytosterols esters (plant sterol andstanol esters); Institute of Food Science and Technology: London, U.K.,2000. (b) http://www.benecol.net/.
(4) (a) Pollak, O. J.; Kritchevsky, D. Phytosterols-sitosterol as cholesteroldepressants. Sitosterol. InMonograph on Atherosclerosis; Karger Basel:Switzerland, 1981; Vol. 10, pp 60-118. (b) O’Neill, F. H.; Brynes, A.;Mandeno, R.; Rendell, N.; Taylor, G.; Seed, M.; Thompson, G. R.Comparison of the effects of dietary plant sterol and stanol esters on lipidmetabolism.Nutr., Metab. CardioVasc. Dis.2004, 14, 133-142. (c) Sugano,M.; Kamo, F.; Ikeda, I.; Morioka, H. Lipid-lowering activity of phytostanolsin rats. Atherosclerosis1976, 24, 301-309. (d) Heinemann, T.; Kullak-Ublick, G. A.; Pietruck, B.; von Bergmann, K. Mechanisms of action ofplant sterols on inhibition of cholesterol absorption. Comparison of sitosteroland sitostanol.Eur. J. Clin. Pharmacol.1991, 40 (Suppl 1), S59-S63. (e)Plat, J.; Mensink, R. P. Increased intestinal ABC A1 expression contributesto the decrease in cholesterol absorption after plant stanol consumption.FASEB J.2002, 16, 1248-1253.
(5) Perry, R.; Green, D.Perry’s Chemical Engineer’s Handbook; Mc-Graw Hill: New York, 1984.
(6) Fogg, P. G. T.; Gerrard, W.Solubility of gases in liquids; Wiley:New York, 1991.
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(8) Haario, H.Modest 6.0 user’s guide; Profmath Oy: Helsinki, Finland,2001.
(9) Helminen, J.; Paatero, E.; Hotanen, U. Hydrogenation of plant sterolsover a polymer fiber-supported Pd catalyst.Org. Process Res. DeV. 2006,10, 51-63.
(10) Moulijn, J. A.; Makkee, M.; va Diepen, A.Chemical processtechnology; Wiley: Chichester, U.K., 2001.
ReceiVed for reView December 22, 2005ReVised manuscript receiVed June 22, 2006
AcceptedAugust 15, 2006
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7076 Ind. Eng. Chem. Res., Vol. 45, No. 21, 2006
