Kinetic Investigations of a Ketonization Reaction Using ReactionCalorimetry

Aljosa Crevatin,‡ Francesco Mascarello,‡ Bettina Leuthe,‡ Bruno Minder,‡ andIreneo Kikic*,†

Chemical, Environmental and Raw Materials Engineering Department, University of Trieste, I-34127 Trieste,Italy, and F. Hoffmann-La Roche Ltd., Vitamins and Fine Chemicals, CH-4070, Basle, Switzerland

The reactor calorimetric technique was employed to study a homogeneous, liquid-phaseketonization reaction used in fine chemical syntheses, where an unsaturated alcohol andunsaturated ether condense to form an unsaturated ketone with higher molecular weight. Theexperiments were carried out in a calorimetric reactor (RC-1) and the data obtained allowedthe determination of reaction heat flow versus time, overall reaction enthalpy, and reactioncourse for experiments at different temperatures. Using the latter data, the conversion versustime behavior was determined. These data were modeled assuming a pseudo-first-order kineticsand an Arrhenius-type temperature dependence of the specific reaction rate. Comparison betweenthese results and the usual concentration versus time experimental data obtained with a differenttechnique was satisfactory.

Introduction

Many fine chemical industrial syntheses, for theproduction of long-chain compounds, use as intermedi-ate reactions the condensation of an unsaturated alcoholand an unsaturated ether to form an unsaturatedketone with higher molecular weight, which is veryuseful for different subsequent reactions in the chainprolongation. They can be usually classified as “Claisen”-type ketonization reactions and are used in perfume,vitamin, and other fine chemical syntheses.1-4 Thegeneral pathway for such reactions5 is presented inFigure 1 where the unsaturated tertiary alcohol (allyl-alcohol) (later A) and the unsaturated ether (later B)condense to form the methyl-ketone (later C) and theketal (later D). This is a homogeneous liquid-phase,acid-catalyzed, exothermic reaction.

The kinetic description and the enthalpy of thereaction are of paramount importance for the reactormodeling and optimization. A reaction calorimetrictechnique was employed for the kinetic investigation ofthe reaction. The experimental data were obtained atdifferent temperatures. Using these data, we couldevaluate the heat of the reaction and therefore theconversion course versus time and the overall reactionenthalpy.

The experimental calorimetric conversion data werecorrelated using a simple kinetic model based on thereaction chemistry. The determined specific reactionrates allowed the description of the kinetics. Comparisonbetween these results and the usual concentrationversus time experimental data was satisfactory andprovided a validation of the method.

Experimental Section

The reported purity of the reagents used was 98.0%for the unsaturated alcohol and 97.5% for the unsatur-

ated ether; the catalyst was a solution of phosphoric acidin acetone. Roche supplied the reagents and the catalystwas from Fluka (phosphoric acid, 99.9%; acetone,99.99%).

Experimental Apparatus. The experiments for thedetermination of the heat of the reaction were carriedout using the reactor calorimeter (RC-1) from the“Mettler Toledo”, schematically represented in Figure2. The main part is the hastelloy steel batch reactor witha nominal volume of 1.8 L and operative temperaturefrom -20 to 250 °C and pressure up to 60 bar. Theheating and cooling of the reactor is provided throughthe reactor jacket, using oil, by the thermostatic RC-1system coupled with an external cryostat. To minimizethe heat losses, the top of the reactor is also heated.The temperature control comprises four thermocouplesfor the measurement of the reactor, jacket, top of thereactor and the cooling oil temperatures, with a preci-sion of (0.001 K. The reactor also has a calibrationsystem (electric heater) to bring into the reactor a veryprecise quantity of heat (QC), which permits one to makethe necessary calibrations during the experiments. Apiezoresistive sensor measures the pressure, with aprecision of (0.01 bar. The stirrer is a four-propellerstirrer with a speed range from 30 to 2500 rpm and arotation momentum measurement system. The reactoris also coupled with a high-pressure pump for the fill-in, a laboratory balance for the mass determination, anda laboratory vacuum pump to remove the air from thereactor. The security system is composed of a stop-solution (NaOH) and a blow-down tank connected to thereactor with a rupture disk valve. The reactor calorim-eter system and all measured parameters are controlledand recorded through an electronic transducer by asoftware computer package.

Experimental Procedure. All experiments werecarried out using stoichiometric reagents molar ratio.The predetermined reagents mass was exactly weightedwith the laboratory balance and then introduced intothe reactor. By the vacuum pump the reactor wasevacuated; successively, nitrogen was introduced. The

* To whom correspondence should be addressed.† University of Trieste.‡ F. Hoffmann-La Roche Ltd.

4629Ind. Eng. Chem. Res. 1999, 38, 4629-4633

10.1021/ie980697l CCC: $18.00 © 1999 American Chemical SocietyPublished on Web 10/26/1999

stirrer speed was set on 1000 rpm to ensure the perfectmixing and to avoid temperature and concentrationgradients. Because the reaction does not occur in theabsence of a catalyst, the reactor was heated to thedesired temperature and a calibration was carried outto determine the overall heat-transfer coefficient andthe flow of total heat loss (base line). At this point,through the pump, the exact quantity of the catalystsolution was filled and the reaction started. During theexperiments the reaction temperature was maintainedconstant and through the control system some calibra-tions allowed the determination of the heat-transfercoefficients. The experimental data collection was longenough to ensure the complete conversion of the re-agents. The complete conversion was verified in anindependent experimental run, using GC analysis of thesamples. The absence of a reaction heat flow and thelinearity of the heat flow curve were then the mainevidence for complete conversion.

Control System. The heat of the reaction wasdetermined on the basis of the heat flow between thereactor and the jacket, or rather on the differencebetween the reaction mass (Tr) and jacket oil (Tj)temperatures. Therefore, the temperature control sys-tem was of paramount importance for the accuracy andreproducibility of the experiments. In Figure 3 thetemperature control system of the reaction calorimeteris illustrated. The reaction mass temperature (Tr) hada proportional control and the jacket temperature (Tj)a proportional-integral one.

Results and Discussion

The investigated ketonization reaction is an exother-mic, irreversible, and very slow reaction. As mentioned

before, the experiments were carried out until thecomplete conversion was reached to maximize thecollection of experimental data and to minimize errorsin experimental data evaluation. As a consequence, theexperimental reaction time was between 10 and 60 h,depending on the reaction temperature. The investi-gated temperatures were 389, 410, 426, and 445 K.

Calorimetric Data Evaluation. The overall heatbalance for the system is expressed as6

and rearranging

Because it is difficult to determine exactly andseparately all terms of eq 1, in the experimental datatreatment they were globally considered as one time-

Figure 1. Reaction scheme.5

Figure 2. Experimental calorimetric equipment.

Figure 3. Scheme of the calorimetric temperature control system.

Qf + Qa ) Qr + QC + Qstir - Qi - Qadd - Qloss (2)

4630 Ind. Eng. Chem. Res., Vol. 38, No. 12, 1999

dependent term Q(t) and the calibration heat flux QCwas assumed negligible in comparison to other fluxes:

where Qb is the sum of all fluxes different from reactionheat flux.

The accumulation term Qa is defined as

and during the reaction, because of isothermal condi-tions, can be considered negligible. The heat fluxthrough the reactor wall is

while the oil film plays an important role because of itsviscosity and low flow, the wall temperature wascalculated from the measured thermostatic oil temper-ature as6

with

The reaction mass is well-mixed by the stirrer andtherefore the effects of the inner film can be assumednegligible.

In the presence of a reacting system the product ofthe overall heat-transfer coefficient and the exchangearea UA changes during the reaction, so it was deter-mined experimentally by calibrations:

These data were correlated along the total reaction time,obtaining their profile, which was then used in eq 5 todetermine the heat flux through the reactor wall.

For the integration, the base line was a linearconnection between the starting and the final Q-con-stant values. In these conditions the reaction does notoccur (Qr ) 0) and from eq 3, the total heat flux Q isequal to Qb. The overall reaction enthalpy was thancalculated by numerical integration in the form

with ∆t being the time interval between two subsequentmeasurements (in the experiments reported, it was 10s).

The reaction enthalpy was ascribed to only onechemical reaction; therefore, from the reaction enthalpy,

the conversion of the reaction on the thermal basis isdefined as

was determined. In Figure 4 the typical calorimetricresults for the experiment carried out at the tempera-ture of 423 K are presented. The course of the reactionheat flow (Q) versus time (curve Q), the base line(dashed line), the integrated area that corresponds tothe reaction enthalpy, and the constancy of the reactortemperature with time (curve T) are clearly evident. Theexperimental conversion, on a thermal basis, is givenby curve X. During the reaction the pressure of thesystem slightly decreases (curve P) with an inversecourse to conversion, due to differences in vapor pres-sures between reagents and products.

The obtained reaction enthalpies (∆Hr) for the differ-ent experiments are -353.2 kJ at 445 K, -348.1 kJ at426 K, and -349.9 kJ at 410 K. Therefore, the experi-mental average reaction enthalpy is -350.4 kJ, andwhile the initial amount of reagent A was 3.856 mol,the mean reaction enthalpy referred to as A is -90.87kJ/mol. When the Joback method7 was used, the calcu-lated enthalpies of formation (∆Hf) for the componentsat 423 K are -250.43 kJ/mol for A, -210.63 kJ/mol forB, -281.70 kJ/mol for C, and -487.80 kJ/mol for D. Thecalculated reaction enthalpy referring to the reagent A,expressed as

is ∆Hrcalc. ) -97.81 kJ/mol. The values are in agree-

ment with each other and the difference is about 7%.This difference can be ascribed to the model predictionerror and to experimental error due to small deviationsin the reaction temperature during the fill-in of thecatalyst.

Kinetic Model Correlation. The investigated ho-mogeneous, liquid-phase, ketonization reaction com-prises the reaction of 1 mol of unsaturated alcohol (A)and 2 mol of unsaturated ether (B) to form 1 mol ofunsaturated ketone (C) and 1 mol of diether (D). Thereaction can than be expressed as

Q(t) ) Qf + Qa ) Qr + Qstir - Qi - Qadd - Qloss )Qr + Qb (3)

Qa ) mrcpr

dTr

dt(4)

Qf ) UA (Tr - Ta) (5)

Ta ) a(T*r - Tr) + b(T*r - Tj) + Tj (6)

a )4r(1 + j)2

j(4 + 3r + 3j + 2rj)and b )

4(1 + j)2

4 + 3r + 3j + 2rj

(r ) 0.4, j ) jf(1.12 + 0.006Tj), and jf ) 0.12)

UA )

∑s

f

QC∆t

∑s

f

(Tr - Ta)∆t

(7)

∆Hr ) ∑[(Q - Qb)∆t] (8)

Figure 4. Experimental curves (experimental data versus time)obtained from the calorimetric control system for the experimentat 426 K. (X ) conversion; P ) pressure (MPa); T ) temperature(K × 10-3); Q ) reaction heat flow (J/min × 105).

X(t) )∆Hr(t)

∆Hr(tf)(9)

∆Hrcalc. ) ∆Hc

f + ∆HDf - ∆HA

f - 2∆HBf (10)

A + 2B 98H+

C + D

Ind. Eng. Chem. Res., Vol. 38, No. 12, 1999 4631

Because the reaction is homogeneous, it takes placein liquid phase, and the volume remains practicallyconstant, for the reaction rate model it was assumedthat the reaction obeys first-order kinetics with respectto the total concentration of reagents A and B. There-fore, the reaction rate equation can be expressed aspseudo-first-order kinetics with respect to conversion8

with k as the reaction rate parameter. When thisequation was used, the experimental calorimetric con-version data for the four different experimental tem-peratures were fitted. The adopted software packagewas “Scientist” (MicroMath), an equation solver andsimulator. The experimental points and the calculatedcurves are presented in Figure 5. The fitting results arevery satisfactory and the specific reaction rates for thedifferent temperatures, the data standard deviations,

where n is the number of points y, and the correlationgoodness between observed (x) and calculated (y) de-pendent values (component concentrations)

are listed in Table 1.

The temperature effect on the reaction kinetics isclearly evident: the reaction rate increases with as-cending temperature. Therefore, the Arrhenius equation

was used to determine the temperature dependence ofthe calculated reaction rate parameters. The reactionrate parameters and the correlated temperature depen-dence are reported in Figure 6. The agreement betweenthe specific reaction rates and the linear temperaturedependence, in the logarithmic diagram, denotes thegoodness of the fitting. The numerical values obtainedfor the activation energy and for the pre-exponentialterm are E ) 64 330 J mol-1 and A0 ) 413 383 min-1,respectively.

Because some of usual concentration versus timeexperimental data for the considered reaction wereavailable,9 a comparison was made between theseresults and those calculated from the developed kineticmodel and is presented in Figure 7. The very goodagreement is a proof of the goodness of the usedcalorimetric analysis to determine the reaction kinetics.

Conclusions

For the kinetics investigation of a homogeneous,liquid-phase, ketonization reaction, the reaction calori-metric technique was employed. The experiments werecarried out at different reaction temperatures.

The determination of the course of the reactionenthalpy was made using a computer-controlled calo-

Figure 5. Experimental conversions from calorimetric data andthe conversions calculated with the obtained reaction model; forthe experiments at 410, 426, and 445 K.

Table 1. Reaction Rate Parameters, StandardDeviations, and Correlation Goodness from theExperimental Data Fitting

exp. temp. (K) 388.85 409.85 426.15 444.85

k (L/min) 0.000 930 0.002 564 0.005 600 0.011 331stand. deviation 0.079 836 0.033 967 0.010 697 0.006 684correlation 0.974 615 0.997 275 0.999 752 0.999 789

dXdt

) k(1 - X) (11)

standard deviation ) x 1

n - 1∑i)1

n

(yi - yj)2,

yj )1

n∑i)1

n

yi (12)

correlation )

∑i)1

n

(xi - xj)(yi - yj)

x∑i)1

n

(xi - x)2x∑i)1

n

(yi - y)2

(13)

Figure 6. Temperature dependence of the reaction rate param-eters correlated with an Arrhenius-type equation.

Figure 7. Experimental conversions from concentration data,experimental conversion from calorimetric data, and the calculatedconversion curve from the kinetic model at T ) 426 K.

k ) A0e-E/RT 98

logln k ) ln A0 -

ER

1T

(14)

4632 Ind. Eng. Chem. Res., Vol. 38, No. 12, 1999

rimetric reactor. The difference between the reactor andjacket temperatures and the determined parameters forthe heat exchange allowed for the determination of theheat of the reaction as a function of time. From thesedata the variation of the conversion with time on thecalorimetric basis was determined.

The conversion data were satisfactorily correlatedwith a pseudo-first-order kinetics model. When theArrhenius equation was used, the temperature depen-dence of the specific reaction rates, the activationenergy, and the pre-exponential term were determined.

The accuracy of the employed calorimetric methodand the developed kinetic model was verified by thecomparison with the usual concentration versus timedata. The good agreement obtained emphasizes the useof the calorimetric method for kinetics investigations.

Notation

A ) unsaturated alcoholA ) wall area, m2

A0 ) pre-exponential term in the Arrhenius equation,min-1

B ) unsaturated etherC ) unsaturated ketoneCA ) molar concentration for component Acpr ) heat capacity of reacting mixture at constant pressure,

J kg-1 K-1

D ) dietherE ) activation energy, J mol-1

e ) Eulero’s number∆Hr ) reaction enthalpyj ) parameter, linear function of the oil temperaturejf ) oil constantK ) kinetic rate parameter, mole min-1

ln ) natural logarithmsmr ) mass of reacting mixtureQ ) total heat fluxQa ) heat flux of accumulation in the reaction massQadd ) other heat flux lossesQb ) basis line for heat fluxQC ) calibration heat fluxQf ) heat flux through the wallQi ) heat flux of accumulation in the insertsQloss ) heat flux through the top of the reactorQr ) heat flux of the reaction,Qstit ) heat flux produced by the stirrer

R ) gas constantr ) film parameter dependent on reactor mass and opera-

tive parametersrA ) reaction raterpm ) stirrer rotation speed, rotations per minT ) temperature, KTa ) reactor wall temperatureTr ) reactor temperatureTj ) reactor jacket temperatureTi ) measured temperatureT* ) corrected temperature by reactor response time

constant (13 s)t ) time, min∆t ) time interval between two measurements, sU ) global heat-transfer parameter, W m-2 K-1

X ) conversion

Literature Cited

(1) Zakharova, P., I.; Miropol’skaya, M. A.; Yurkina, O. T.;Filippova, T. M.; Kustanovich, I. M.; Samokhvalov, G. I. Prepara-tion and Rearrangement of Acetone Methyl. Zh. Org. Khim. 1971,7, 1137.

(2) Attenburrow, J.; Cameron, A. F. B.; Hapman, J. H.; Evans,R. M.; Hems, B. A.; Jansen, A. B. A.; Walker, T. A Synthesis ofVitamin A from Cyclohexanone. J. Am. Chem. Soc. 1951, 73, 1094.

(3) Isler, O.; Ronco, A.; Guex, W.; Hindley, N. C.; Huber, W.;Dialer, K.; Kofler, M. Ueber die Ester und Aether des synthetis-chen Vitamins A. Helv. Chim. Acta 1949, 32 (63), 489.

(4) Graffin, P.; Julia, S.; Julia, M. Transposition HomoallyliqueVinylogue d’Alcools R,â,γ,δ-Dieniques ε-Cyclopropaniques. Mem.Pres. Soc. Chim. 1964, 517, 3218.

(5) Saucy, G.; Marbet, R. Ueber die Reaktion von tertiaerenVinylcarbinolen mit Isopropenylaether. Eine neue Methode zurHestellung von γ,δ-Ungesaettigten Ketonen. Helv. Chim. Acta1967, 50 (218), 2091.

(6) Mettler Toledo, Manual RC-1; Mettler Toledo, 1995.(7) Reid, R. C.; Prausnitz, J. M.; Poling, B. E. The Properties of

Gases and Liquids; McGraw-Hill: New York, 1987.(8) Marbet, R.; Saucy, G.; Ueber eine neuartige Synthese von

â-Kettoallenen durch Reaktion von tertiaeren Acetylencarbinolenmit Vinylaethern. Eine ergiebige Methode zur Darstellung desPseudojonons und verwandter Verbindungen. Helv. Chim. Acta1967, 50 (119), 1158.

(9) F. Hoffman-LaRoche Ltd., Internal Report, 1997.

Received for review November 5, 1998Revised manuscript received April 8, 1999

Accepted September 12, 1999

IE980697L

Ind. Eng. Chem. Res., Vol. 38, No. 12, 1999 4633