Evaluation of kinetic data with an automatically working laboratory unit

Pergamon

Chemical Engineering Science, Vol. 5I, No. I l. pp. 2909-2914, 1996

Copyright© 1996ElsevierScienceLtd Printedin GreatBritain. All rightsreserved 0009-2509/96 $15.00+ 0.00

S0009-2509(96)00173-X

EVALUATION AUTOMATICALLY

OF KINETIC

DATA WITH

WORKING

LABORATORY

AN UNIT

B. KRUGER, H. ZIEMER, M. MERTL, TH. BAYER Itoechst AG. Verfahrenstechnik,G811, 65926 Frankfurt

Abstract - For the automation of the evaluation of kinetic data, we have built up a modular laboratory unit with three difl'erent continuously working gradientless reactors (CSTR, double-mixed-contactor,betty-reactor). The experimental plan and the laboratory unit are controlled by a process-control-systemIn the CSTR we have determinedkinetic data for a three-phase enzymatic reaction The NO-absorptionwas part of our resarch in the double-mixed-contactor. The results of our investigation and the problem of automation are the content of this paper.

A U T O M A T I O N O F D E T E R M I N I N G K I N E T I C DATA

A major problem in research of reaction kinetics is the evaluation of experimental data, which lead to useful micro-, macro- or formal kinetic models. In the past, different types of reactors have been developed to increase accuracy o f experimental data. The idea of working with gradientless reactors, which simplify the calculation of reaction kinetics, has been established for almost all reaction systems. Three different types of reactors, which are the CSTR for gas-liquid-solid reactions, the berty-Reactor for heterogenous gas-solid reactions and the double-mixed-contactor for gas-liquid reactions enable to determine kinetic data in industrially relevant systems. Aim of our work was to develop a modular unit, which essentially consists of three components and works with a high degree of automation. The modular components are a dosing unit for liquids and gases, three different reactor units and an online-analytical unit. Automation includes controlling of individual components of the units as well as management of an experimental plan. To reach a high degree of automation we use a process-control-syslem (PLS). It allows the control of dosing, reaction parameters (partial pressures, pH, temperature ...) and collection of analytical data in an easy way. Furthermore we can incorporate an experimental plan with the theoretical background of reaction kinetics. Such a system is able to decide whether measured experimental data are useful for evaluation or whether further measurements are necessary. Influence of several reaction parameters can be evaluated independently. Advantage of the unit is the continuous mode of the reactors. Therefore periods of time to get useful data and manpower necessary for the measurements are minimized. The concept of the unit is shown schematically in Fig. 1. An external PC is used tbr creating the configuration of the process-control-system. Configuration with an experimental plan is sent to the process-control-system. A permanent data transfer from PLS to dosing, reactor and analytical unit takes place. The dosing unit has different pumps for liquid-dosing, liquid-flow-controllers and mass-flow-controllers for gases. Types of reactors used for the different reactionsystem, are the CSTR, the double-mixed-contactor and the berry-reactor. For online-analytics we use HPLC and GC. For controlling reactor concentrations, we use those analytical results, which are sent to the PLS. Step by step the PLS checks the reactor concentrations and changes, if necessary, dosing parameters to control the concentration or continues in the experimental plan. 2909

2910

B. KRUGER et al.

GRADIENTLESS REACTORS Concept of Automation for determining kinetic parameters Experimental plan Evaluation Modelling

4t Process control system 1. process control 2. data registration GILLS

4

G/L

tt

Online-Analytic

Dosing 1. Gas 2. Liquid

Fig. 1

t

G/S

1. CSTR 2. Double mixed contactor 3. Berry-Reactor

Concept of the modular and automated laboratory unit

1. GC 2. HPLC

Evaluation of kinetic data

2911

AUTOMATION OF KINETIC EVALUATION FOR THREE-PHASE-REACTIONS

The first reaction we investigated in our automated unit was the first step of the enzymatically catalysed synthesis of 7-aminocephalosporanic acid (7-ACA). It is the oxidation of cephalosporin C (CPC) to glutaryl-7ACA (G-7-ACA). The three phases of the reaction are the aqueous solution of CPC, oxygen in the gas-phase and the catalyst, which is D-amino acid oxidase (DAAO) on a solid polymersupport. The reaction of G7-ACA with glutarylamidase (GA) to 7-ACA was not part of our research. The reaction scheme to the final product 7-aminocephalosporanic acid is shown in Fig. 2. In the first step of the reaction CPC is oxidized with the catalyst DAAO to O~ -keto-7-ACA (k-7-ACA). The k-7-ACA reacts with the intermediate hydrogen peroxide to G-7-ACA. Ammonia and carbondioxide are byproducts. The reaction is influenced by the CPC-concentration, the oxygen-partial pressure, the pH and the reaction-temperature.

NH2

O

S

N

-CH2-O-~-CH 3

O

cephalosporin C (CPC), C~6H21OsN3S MW: 415,4 g/mol

COOH

+ D-amino acidoxidase (D,~O)

0

~

+%

0

.ooc_cU..ic.2~3_~...

-

s

o

C~-keto-adipinyt-7-aminocephalosporanicacid (K-7-ACA), C18H18OgN2S MW: 414,4 g/mol

1~

+H202 -C%

0 HOOC'(CH2)3"(~'NH"[ ~ S

~'~

O

glutaryl-7-aminocephalosporanicacid (G-7-ACA), C1sH18OsN2S MW: 386,4 g/mol

1~ " ~ +H20 + glutaryl-7-ACAacylase (GA)

J.

HOOC-(CH2)3-COOH

$

-CH2-O-OH3

7-amino-cephalosporanicacid (7-ACA), 010H12OsN2S MW: 272,3 g/mol

COOH

Fig.2

Reactionscheme lbr the 7-ACAreaction

2912

B. KROGERet aL

Our model for the first step of the reaction kinetics is based on literature of Tischer et al. (1993), Dunn et al. (1992), Giesecke (1992) and has been independently conf'u'med with batch experiments in our laboratory. The reaction rates for the reaction system are given in Eq. 1. to 6. The model is based on the well known MichaelisMenten-Kinetics for enzymatic reactions.

dC CPC,I

Vmax " C cPc ,I =

dt

k.,ce c +ccI.C, '

Co 2 ,I

ki

" "

dC KA,I

k~'°~ +c°~'t

.J

Vmax " C cPc ,l

Co 2 ,I

¢

dt

k.,,o2

k,,, cec + ccpca" |1 + ~*~"1 •

dCGA'I dt

=

\

+

- k2 "cH~o, ,~ Cr~ a - ki - Cr.Aj

Vmax " C cPc ,I

Co 2 ,I

"/l+ Ccec.t I ki

'

dc°2; _ k , aO2.(Co2, _Co,,,)_ dt

km(,PC

"

Eq.

3

Eq. 4

dt

k,.cvc +Cceca

2

)

k,

dC Np'---------J-I-- k l . ( C c P c , I + CGA,I -+- C KA,I )

dt

Eq.

Co 2

k2 "CH=o,,z "cx~,~ - ki • c~a,~

dC H202 ,I

Eq. 1

- k I • CoPe, t

-(1+%'<#1

- k 2 • C~2o~,~ • c~,~

- k 3 • Cr~,l Eq.5

km,o2 +Coax

)

Vmax"CcPc ,I +CcPc,' .(1+

Co 2,I CcPc'II

Eq.6

km'°: +C02'1

k, J

With the concept of gradientless reactors we can measure the reaction-rate of CPC directly Eq.7.

Pc=- % • (CcPc't ""

- Ccl"c't )

Eq. 7

V. With three pumps controlled by the PLS and the HPLC we were able to control the CPC-concentration. The oxygen-concentration was measured with an oxygen-sensor. To control the gas/liquid mass-transfer the oxygenpartial pressure and stirrer speed could be changed. The pH-dependence of the reaction could be determined by pH-variation controlled by the PLS. The reaction temperature was equally controlled by the PLS. The liquid volume is controlled by an opto-electronical device.

With the online-HPLC results and the given set-points of the experimental plan in the worksheet of the PLS we were able to determine the parameters of reaction kinetics.

2913

Evaluation of kinetic data

A U T O M A T I O N O F KINETIC EVALUATION FOR GAS/LIQUID-REACTIONS

For many technical reactions the combination of mass-transfer and chemical reaction is important. The NOabsorption is interesting in the nitric-acid-process and the removal as pollutant from air. In the azo-dyes-process the NO-absorption is part of the safety-concept. Based on literature data, Sada, Kumazawa, Kudo and Kondo (1978) and Blumhofer and Weisweiler (1983), we studied the NO-absorption in a double-mixed-contactor. The solubility of NO in water is small. Therefore it is necessary to oxidize the NO to NO2 in the liquid phase to keep the concentration gradient between gas- and liquid-phase at a high level. The oxidation can be achieved with different absorbents in the liquid phase. To separate chemical kinetics from mass transfer we created an experimental plan with the following parameters: the NO-partial pressure:, the absorbant concentration, the surface area, the residence time and the pH of the liquid phase. The NO partial pressure was controlled by GC-online analytic and the dosing unit. The residence time for the gas-phase is given by the gas volume and the flow controller, and for the liquid-phase by the liquid volume and pumps in combination with flow-controllers. The reactor volume is controlled by an optoelectronical device and a pump. With this concept both liquid- and gas-phase are continuously working. With Eq.8 and Eq.9 we have been able to determine the mass transfer of NO into the liquid~phase and the following chemical-reaction. gas-phase:

k l a ,vo

. ( c N~;,I

_ c,vo,/) =

J/;'g (C e ill . au', ) NO ,g -- C NO.g

Eq.8

VR

liquid-phase:

*

Ryo =

k ~a A'O . ( C NO,[ -- C NO,I ) --

~/;l(t.. ¢in - - C .... ) ab;.I ab.~ ,l Eq.9

VI¢

CONCLUSION

With our concept we have shown that it is possible to build up a modular and automated laboratory unit to measure reliable kinetic data. The idea to use a PLS in the laboratory is to control the different parts of the unit and to include an experimental plan in the PLS, which enables us to reach a high degree of automation. With two reactions, a three-phase enzymatic reaction and the NO-absorption, we proofed our concept on basis of literature results.

2914

B. KRUGERet al.

NOTATION

k ,,,cl,( :

reaction rate CPC maximum of the reaction rate Michaelis-Menten (CPC)

[mol/(m 3 s)] [mol/(m 3 s)] [mol/m 3]

k nl,O

Michaelis-Menten (02 )

[mol/m 3]

ki

Inhibition by CPC

[mol/m 3]

kl

desacetylation rate

[s-~]

k2

decarboxylation rate

[m3mol%1]

k3 kl a o2

hydrogenperoxide decomposition

[s-~]

Oxygen mass-transfer-coefficient

[s~]

C('PC,I

concentration of CPC

[mol/m 3]

CGA,I

Glutaryl-7ACA

[mol/m 3]

Rcpc Vmax

(/. -keto-7-ACA

[mol/m 3]

C NP,I

Byprodukts

[mol/m 3]

C H202 ,I

concentration of H~O2

[mol/m 3]

concentration of Oz

[mol/m 3]

02 -solubility

[mol/m 3]

CPC concentration at inlet

[mol/m ~ ]

RNo k~ aN°

CPC concentration at outlet reaction rate NO NO mass-transfer-coefficient

[mol/m 3 ] [mol/(m 3 s)] [s-~]

C em NO,g

NO concentration at gasinlet

[mol/m 3 ]

C ~1115 NO ,g

NO concentration at gasoutlet

[mol/m 3 ]

C NO,I

NO -solubility

[mol/m 3]

C NO ,I

N O -concentration

[mo l/m~]

ein C ab.~,I

Absorbant concentration at inlet

[mol/m 3 ]

C ahs,l au.s

Absorbant concentration at outlet reactor volume

[mol/m 3 ] [m3 ]

volume rate of liquid-phase

[m 3/s]

volume rate of gas-phase

[m 3/s]

C KA ,I

CO 2 ,I C o 2 ,1 ein C(T(,,I C(7,(,,l

VR

REFERENCES

W. Tischer et al., 1993, Enzyme Engineering XI, pp. 502-509 Dunn et al., 1992, VCH, pp. 383 U. E. Giesecke et al., 1992, DECHEMA B iotechnology Conferences, 5, pp. 609-613 E. Sada, H. Kumazawa, 1. Kudo, T.Kondo, 1978, Chemical Engineering Science, Vol 33, pp. 315-318 R. Blumhofer, W. Weisweiler, 1983, Chem.-lng.-Tech., 55, Nr. 10, pp. 810-811