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The effect of mixing on scaleup of a parallel reaction system
Clvmical Engh?etir#g Science, Printed in Gfeat Britain.
Vol.
47,
No. 9-11.
pp. 2837-2840.
1992.
0
THE EFFECT OF MIXING ON SCALEUP PARALLEL REACTION SYSTEM E L. Paul, H. Mahadevau,
ooo9-25ow92 1992 Pcq-n
s5.oo+o.co Rcss
Ltd
OF A
J. Foster, M. Kennedy, M. Mid&
Merck & Co., Inc., P.O. Box 2000, Rahway, N.J. 07065, USA
ABSTRACT The study of the effect of mixing on parallel reactions can be effectively utilized to provide information on local micromixing as well as to define the mixing requirements for this important class of industrial applications. Parallel reactions can be either part of the inherent reaction system or can be encountered in neutralization of mixtures containing labile substrates. These effects must be considered in scale-up of reaction systems in which mixing sensitivity may be significant-
INTRODUCTION
required to achieve mixing on the molecular scale as required for complete neutralization of the added reagent.
Parallel reactions are encountered in industrial processes to a lesser extent than consecutive reactions. For that reason, they have not received as much attention from a mixing and scale-up point of view as have the cousecutive, competitive type. Two recent papers (Baldyga and Boume, 1990 and Boume and Yu, 1991) have demonstrated the importance of mixing in the determination of product distribution for parallel reactions. The kinetic differences were used to predict theoretical product distributions, which were compared to actual distribution in experimental systems. Differences between theoretical and actual results were used as a measure of actual mixing intensity in the contacting of the reagents.
For the reaction system
A+B
kl_
P
A-t-C
L
Q
where A is added to neutralize B in the presence of a substrate C, the ratio of P to Q should be a direct function of the ratio of the reaction rates. In this analysis, P would be the water formed in the neutralization reaction and Q would be symbolic of a reaction byproduct of A reacting with the substrate C instead of neutralizing B.
An industrially significant application of these effects may be experienced in the common practice of addition of acids or bases to adjust pH in the presence of a labile substrate. Depending on the decomposition rate of the substrate in the presence of high (or low) pH,, a significant amount of degradation could occur during the course of a pH adjustment. This would be caused by local high concentrations of the base (or acid) in the zone of addition because of the finite time
In most cases, the rate of the neutralization reaction will be so much faster than the parallel reaction of C to Q that no Q would be formed. However, there may be substrates that are sufficiently labile for some finite parallel reaction to occur because of imperfect mixing on the molecular scale. The actual degree of conversion may be very small but in certain cases this degradation could be significant in terms of byproduct formation. The criticality 2837
E. L. PAUL et aI.
2838
H3
of the mixing requirements may not be recognized at the laboratory scale but may become apparent in plant scale operation.
LABORATORY
The above parallel reaction system was further studied in the laboratory to quantify the changes in yield as a function of impeller speed and feed position. The results of this experimental work are shown in Figures 1 and 2 where the amount of the byproduct of hydrolysis, Q, is used as the response variable. The amount of Q is measured by HPLC in the final neutralized mixture after pH adjustment from pH 2 to pH 7 with aqueous sodium hydroxide.
EXAMPLE REACTION SYSTEM: PLANT SCALE Neutralization of a labile substrate is analyzed in the following example. In this case the substrate is in solution in an organic solvent and aqueous sodium hydroxide is added to raise the pH from pH 2 to 7. The rapid parallel reactions are acid-base the neutralization and a base-catalyzed hydrolysis as shown:
OH(A)
OH-
+
H30+
k1 =_
2H20
03)
09
‘--OR
+
0
(A)
(0
Enolization occurs under basic conditions, subjecting the substrate to possible irreversible decomposition (ring opening). This neutralization was in pIant operation when a detailed analysis revealed that the indicated parallel hydrolysis was occuring to a significant extent. This observation was confirmed in a laboratory study. A significant yield increase was realized by a change from sodium hydroxide to sodium bicarbonate as the neutralizing base because of the reduction in local pH gradients.
SMJDIRS
J,
I
6
+HCOO0
CQ) In Fig.1, the amount of Q formed is shown to be a function of impeller speed in a .006 m3 fully baffled vessel with a 7.2 cm. six-bladed Rushton turbine. The absolute value of the hydrolysis rate constant, k2. is not known in this pH range but has been observed to be many orders of magnitude lower than the acid-base neutralization rate. Therefore, the significant amounts of Q shown in Fig. 1 can only result from local high concentrations of base, where the high pH would cause the hydrolysis reaction rate to be competitive with that of the acid-base neutrallzadon.
Effect of mixing on scaleup of padIe
H3
2839
reaction system
0.1
0.08
0.06
0.04
0.02
0 50
100
200
150
Turbine Figure
RPM
250
300
1
FractionByproduct(Q/C Ratiio) versusRPM (7.ON NaOH addition)
In Fig. 2, the changes in the amount of Q formed at constant impeller speed are the result of changes in feed position. At 3.3 s-1 the two liquid phases (methylene chloride/water) are not uniformly blended. Addition of base (7N in all cases) to the upper portion of the vessel, where the mixture is
aqueous-rich, results in local dilution before reaction and in a lower amount of Q. On the other hand. additionof the base to the solventrich lower portion resnltsin higher levels of Q formationbecause of reduced local dilution.
Feed Tube
o.oo8°16 Q (Feed Tube in Upper Section)
Region of good 0.014% Q (Feed Tube as Shown)
O.O27?h Q (Feed Tube in Lower Section)
Effect of Feed Tube Location on ByproductFormation (200RPM, 7.ON NxOH addition)
H3
E. L. PAUL etai.
2840
MACRO-
VERSUS MICROMIXING
Although base was added to the mixed vessel slowly to minimize the effect of imperfect macromixing in the vessel, the effect of mixing parameters on yield observed in this cannot be ascribed solely to work micromixing without additional analysis of flow generated by the impeller. Such a model (Mann and El-Hamouz, 1991) has recently been used to evaluate the macromixing limitations in a competitive/consecutive reaction system. CONCLUSIONS The expected effect of mixing on a system of fast parallel reactions has been determined experiment.aIly. The results have been used to make a significant change in a manufacturing operation involving an acid-base neutralization step. The effects of imperfect mixing are expected to be more pronounced at the manufacturing scale thereby making analyses of this type industriallysignificant.
BIBLIOGRAPHY Baldyga, J. and Boume, J. R., 1990, The effect of micromixing on parallel reactions. Chemical Engineering Science 45. 907-916. Bourne, J. R_ and Yu. S.. 1991, An experimental study of micromixmg using two parallel reactions. Proc. 7th European Conference on Mixing, pp 67-76, Brugges. Belgium. Mann, R. and El-Hamouz, 1991. Effect of macromixing on a competitive/consecutive reaction in a semi-batch stirred reactor: Paul’s experiments interpreted by iodination networks of zones, Proc. 7th European Conference on Mixing. pp l-8. Brugges. Belgium.
Vol.
47,
No. 9-11.
pp. 2837-2840.
1992.
0
THE EFFECT OF MIXING ON SCALEUP PARALLEL REACTION SYSTEM E L. Paul, H. Mahadevau,
ooo9-25ow92 1992 Pcq-n
s5.oo+o.co Rcss
Ltd
OF A
J. Foster, M. Kennedy, M. Mid&
Merck & Co., Inc., P.O. Box 2000, Rahway, N.J. 07065, USA
ABSTRACT The study of the effect of mixing on parallel reactions can be effectively utilized to provide information on local micromixing as well as to define the mixing requirements for this important class of industrial applications. Parallel reactions can be either part of the inherent reaction system or can be encountered in neutralization of mixtures containing labile substrates. These effects must be considered in scale-up of reaction systems in which mixing sensitivity may be significant-
INTRODUCTION
required to achieve mixing on the molecular scale as required for complete neutralization of the added reagent.
Parallel reactions are encountered in industrial processes to a lesser extent than consecutive reactions. For that reason, they have not received as much attention from a mixing and scale-up point of view as have the cousecutive, competitive type. Two recent papers (Baldyga and Boume, 1990 and Boume and Yu, 1991) have demonstrated the importance of mixing in the determination of product distribution for parallel reactions. The kinetic differences were used to predict theoretical product distributions, which were compared to actual distribution in experimental systems. Differences between theoretical and actual results were used as a measure of actual mixing intensity in the contacting of the reagents.
For the reaction system
A+B
kl_
P
A-t-C
L
Q
where A is added to neutralize B in the presence of a substrate C, the ratio of P to Q should be a direct function of the ratio of the reaction rates. In this analysis, P would be the water formed in the neutralization reaction and Q would be symbolic of a reaction byproduct of A reacting with the substrate C instead of neutralizing B.
An industrially significant application of these effects may be experienced in the common practice of addition of acids or bases to adjust pH in the presence of a labile substrate. Depending on the decomposition rate of the substrate in the presence of high (or low) pH,, a significant amount of degradation could occur during the course of a pH adjustment. This would be caused by local high concentrations of the base (or acid) in the zone of addition because of the finite time
In most cases, the rate of the neutralization reaction will be so much faster than the parallel reaction of C to Q that no Q would be formed. However, there may be substrates that are sufficiently labile for some finite parallel reaction to occur because of imperfect mixing on the molecular scale. The actual degree of conversion may be very small but in certain cases this degradation could be significant in terms of byproduct formation. The criticality 2837
E. L. PAUL et aI.
2838
H3
of the mixing requirements may not be recognized at the laboratory scale but may become apparent in plant scale operation.
LABORATORY
The above parallel reaction system was further studied in the laboratory to quantify the changes in yield as a function of impeller speed and feed position. The results of this experimental work are shown in Figures 1 and 2 where the amount of the byproduct of hydrolysis, Q, is used as the response variable. The amount of Q is measured by HPLC in the final neutralized mixture after pH adjustment from pH 2 to pH 7 with aqueous sodium hydroxide.
EXAMPLE REACTION SYSTEM: PLANT SCALE Neutralization of a labile substrate is analyzed in the following example. In this case the substrate is in solution in an organic solvent and aqueous sodium hydroxide is added to raise the pH from pH 2 to 7. The rapid parallel reactions are acid-base the neutralization and a base-catalyzed hydrolysis as shown:
OH(A)
OH-
+
H30+
k1 =_
2H20
03)
09
‘--OR
+
0
(A)
(0
Enolization occurs under basic conditions, subjecting the substrate to possible irreversible decomposition (ring opening). This neutralization was in pIant operation when a detailed analysis revealed that the indicated parallel hydrolysis was occuring to a significant extent. This observation was confirmed in a laboratory study. A significant yield increase was realized by a change from sodium hydroxide to sodium bicarbonate as the neutralizing base because of the reduction in local pH gradients.
SMJDIRS
J,
I
6
+HCOO0
CQ) In Fig.1, the amount of Q formed is shown to be a function of impeller speed in a .006 m3 fully baffled vessel with a 7.2 cm. six-bladed Rushton turbine. The absolute value of the hydrolysis rate constant, k2. is not known in this pH range but has been observed to be many orders of magnitude lower than the acid-base neutralization rate. Therefore, the significant amounts of Q shown in Fig. 1 can only result from local high concentrations of base, where the high pH would cause the hydrolysis reaction rate to be competitive with that of the acid-base neutrallzadon.
Effect of mixing on scaleup of padIe
H3
2839
reaction system
0.1
0.08
0.06
0.04
0.02
0 50
100
200
150
Turbine Figure
RPM
250
300
1
FractionByproduct(Q/C Ratiio) versusRPM (7.ON NaOH addition)
In Fig. 2, the changes in the amount of Q formed at constant impeller speed are the result of changes in feed position. At 3.3 s-1 the two liquid phases (methylene chloride/water) are not uniformly blended. Addition of base (7N in all cases) to the upper portion of the vessel, where the mixture is
aqueous-rich, results in local dilution before reaction and in a lower amount of Q. On the other hand. additionof the base to the solventrich lower portion resnltsin higher levels of Q formationbecause of reduced local dilution.
Feed Tube
o.oo8°16 Q (Feed Tube in Upper Section)
Region of good 0.014% Q (Feed Tube as Shown)
O.O27?h Q (Feed Tube in Lower Section)
Effect of Feed Tube Location on ByproductFormation (200RPM, 7.ON NxOH addition)
H3
E. L. PAUL etai.
2840
MACRO-
VERSUS MICROMIXING
Although base was added to the mixed vessel slowly to minimize the effect of imperfect macromixing in the vessel, the effect of mixing parameters on yield observed in this cannot be ascribed solely to work micromixing without additional analysis of flow generated by the impeller. Such a model (Mann and El-Hamouz, 1991) has recently been used to evaluate the macromixing limitations in a competitive/consecutive reaction system. CONCLUSIONS The expected effect of mixing on a system of fast parallel reactions has been determined experiment.aIly. The results have been used to make a significant change in a manufacturing operation involving an acid-base neutralization step. The effects of imperfect mixing are expected to be more pronounced at the manufacturing scale thereby making analyses of this type industriallysignificant.
BIBLIOGRAPHY Baldyga, J. and Boume, J. R., 1990, The effect of micromixing on parallel reactions. Chemical Engineering Science 45. 907-916. Bourne, J. R_ and Yu. S.. 1991, An experimental study of micromixmg using two parallel reactions. Proc. 7th European Conference on Mixing, pp 67-76, Brugges. Belgium. Mann, R. and El-Hamouz, 1991. Effect of macromixing on a competitive/consecutive reaction in a semi-batch stirred reactor: Paul’s experiments interpreted by iodination networks of zones, Proc. 7th European Conference on Mixing. pp l-8. Brugges. Belgium.