- Batch Reactor vs CSTR
- CSTR Design
- PFR vs CSTR
- Advantages and Disadvantages
- CSTR Residence Time Distribution (RTD)
- Modeling and Simulation of CSTRs
- PAT Integration
- Industry Applications
- Citations and References
- FAQs
What is a Continuous Stirred Tank Reactor?
A continuous stirred tank reactor (CSTR) is a reaction vessel in which reagents, reactants, and solvents flow into the reactor while the products of the reaction concurrently exit the vessel. In this manner, the tank reactor is considered to be a valuable tool for continuous chemical processing.
CSTR reactors are known for their efficient mixing and stable, uniform performance under steady-state conditions. Typically, the output composition is the same as the material inside the reactor, which depends on the residence time and reaction rate.
In situations where a reaction is too slow, when two immiscible or viscous liquids require a high agitation rate, or when plug flow behavior is desired, multiple reactors can be linked together to create a CSTR cascade.
A CSTR assumes an ideal backmixing scenario, which is the exact opposite of a plug flow reactor (PFR).
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CSTR vs Batch Reactor
In general, reactors can be classified as either continuous (Fig. 1) or batch reactors (Fig. 2). CSTRs are typically smaller in size and enable the seamless addition of reactants and reagents while the product can flow out continuously without interruption.
In contrast, a batch reactor is a chemical reactor that involves the addition of a fixed amount of reactants to the reactor vessel, followed by the reaction process until the desired product is obtained. Unlike a continuous reactor, reactants are not added continuously, and products are not removed continuously. Furthermore, batch reactors are not as uniformly mixed, and the temperature and pressure conditions may vary during the reaction.
CSTRs have the unique ability to handle higher reactant concentrations, as well as more energetic reactions due to their superior heat transfer properties in comparison to batch reactors. In this manner, a CSTR is considered a tool supporting flow chemistry.
Design and Operation of CSTRs
Continuous stirred tank reactors (CSTRs) consist of:
- A tank reactor
- Stirring system to mix reactants (impeller or fast-flowing introduction of reactants)
- Feed and exit pipes to introduce reactants and remove products
CSTRs are most commonly used in industrial processing, primarily in homogeneous liquid-phase flow reactions where constant agitation is required. However, they are also used in the pharmaceutical industry and for biological processes, such as cell cultures and fermenters.
CSTRs may be used in a cascade application (Fig. 3) or standalone (Fig. 1).
CSTR and PFR
What Is the Difference Between CSTR and PFR (plug flow reactor)?
CSTRs (Fig. 1) and PFRs (Fig. 4) are both used in continuous flow chemistry. CSTRs and PFRs can either function as standalone reaction systems or be combined to form part of a continuous flow process. Mixing is a crucial aspect of CSTRs, whereas PFRs are designed as tubular reactors where individual moving plugs contain reactants and reagents, acting as mini-batch reactors. Each plug in a PFR has a slightly different composition, and they internally mix, but not with the nearby plug ahead of or behind it. In an ideally mixed CSTR, product composition is uniform throughout the entire volume, whereas in a PFR, product composition varies depending on its position within the tubular reactor. Each type of reactor has its own set of advantages and disadvantages when compared to the others.
While a CSTR can produce substantial quantities of product per unit of time and can operate for extended periods, it may not be the best choice for reactions with slow kinetics. In such cases, batch reactors are typically the preferred option for synthesis.
Plug flow reactors are generally more space-efficient and have higher conversion rates compared to other types of reactors. However, they are not suitable for highly exothermic reactions because it can be challenging to control sudden temperature surges. Furthermore, PFRs typically entail higher operating and maintenance costs than CSTRs.
Advantages of CSTR over PFR
- Temperature control is easily maintained
- CSTR behavior is well understood, including in mixing (ability to handle solids and slurries), reaction calorimetry, dosing options, and chemical kinetics
- Less expensive and easier to construct than dedicated specialty flow systems
- The interior of the reactor is accessible for process analytical technology (PAT)
- Multiple units can be easily joined for cascade operation or integration in more complex flow systems with PFR, etc.
Optimization of CSTR Performance
CSTR Residence Time Distribution (RTD)
Residence time distribution (RTD) describes the duration that a fluid component stays in a system or a reactor. CSTR residence time relates to the time that reactants spend in the reactor before they leave it.
Understanding the residence time distribution of a CSTR is critical in designing and optimizing reactors for chemical reactions. It helps in evaluating the reactor's efficiency and the duration required to achieve a complete reaction. Deviation from ideality can result from the channeling of fluid through the vessel, recycling of fluid within the vessel, or the presence of poorly mixed or stationary regions in the vessel. As a result, a probability distribution function, RTD, is used to describe the amount of time that any finite portion of the fluid resides in the reactor. This helps to characterize the mixing and flow characteristics in the reactor and to compare the behavior of the reactor to ideal models. For example, a cascade of CSTRs exhibits tighter residence time and reaction resolution as the number of reactors increases in the cascade setup.
The residence time distribution of a fluid in a vessel can be experimentally determined by the addition of a non-reactive tracer substance into the system inlet. The concentration of this tracer is varied by a known function and overall flow conditions in the vessel are determined by tracking the concentration of the tracer in the effluent of the vessel.
Modeling for Greener Chemistry
Green and sustainable chemistry is a growing trend in the pharmaceutical and fine chemical industries. This approach to chemistry aims to minimize the environmental impact of chemical processes by reducing waste and energy consumption, using renewable resources, and designing processes that are safe and efficient.
By using modeling software, scientists and engineers can predict how chemical reactions will behave under different conditions, optimize reaction conditions to reduce waste and energy consumption, and design processes that are safer and more efficient. For example, evaluations of batch versus flow chemistry can be made quickly, or determining CSTRs sized for best performance. Continuous processes may be more sustainable than batch, for reasons such as lower volume, less solvent usage, and reduced cleaning cycles.
Chemical reaction modeling and simulation are particularly well-suited to support green chemistry initiatives. Scale-up Suite's advanced modeling capabilities enable users to accurately simulate complex chemical reactions, including multi-step reactions and optimize process parameters such as temperature, pressure, and reactant concentrations to minimize waste and maximize yield.
Scale-up Suite™ also has features that allow users to assess the environmental impact of their processes, such as calculating the carbon footprint or energy consumption of a given reaction. This information can help users make informed decisions about process design and identify opportunities to make their processes more sustainable.
CSTR and Process Analytical Technology (PAT)
Automated lab-scale chemical reactors can help convert from batch to CSTR operation.
- Parallel synthesis reactors such as EasyMax have multiple well-controlled independent reactors that can be used individually or together as CSTRs
- Synthesis reactors and reactor control systems can operate as single CSTR systems or couple to other reactors controlled from the same PC
- For crystallizations or multi-phase reactions, pressure difference can be used to transfer slurries
Process analytical technology is invaluable in keeping steady state monitored and well controlled.
- FTIR spectroscopy and Raman spectroscopy provide real-time measurement of critical reaction species.
- For example, in continuous crystallizations, FTIR spectrometers can measure and present steady state concentration of one or more key solutes.
- Raman spectrometers measure and monitor crystal form development as a function of time
- ParticleTrack uses Focused Beam Reflectance Measurement (FBRM) to monitor key crystallization parameters, including particle size distribution and chord length
- pH and O₂ probes continually monitor conditions in CSTR - as required
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Industry Applications
Continuous Process for Safe Production of Diazomethane
ReactIR monitors the Diazoketone concentration and is used for RTD determination
The authors report the development of a diazomethane generator consisting of a CSTR cascade with internal membrane separation technology. They used this technology in a three-step, telescoped synthesis of a chiral α-chloroketone – an important intermediate compound in the synthesis of HIV protease inhibitors. A coil reactor was used to generate a mixed anhydride that was passed into the CSTR diazomethane cascade. The Teflon membrane allowed diffusion of the diazomethane into the CSTR where it reacted with the anhydride to form the corresponding diazoketone. The diazoketone was then converted to the α-chloroketone by reaction with HCl in a batch reactor.
ReactIR measurements were used to follow the formation of the intermediate diazoketone compound (tracking 2107 cm-1 peak) and also to experimentally determine the residence time distribution for the system by tracking the tracer substance. The tracer experiment monitored by ReactIR determined that five reactor volumes of the second CSTR in the cascade were required to reach steady state, corresponding to a 6-hour start-up time.
Wernik, M., Poechlauer, P., Schmoelzer, C., Dallinger, D., & Kappe, C. O. (2019). Design and Optimization of a Continuous Stirred Tank Reactor Cascade for Membrane-Based Diazomethane Production: Synthesis of α-Chloroketones. Organic Process Research & Development, 23(7), 1359–1368. https://doi.org/10.1021/acs.oprd.9b00115
Automated Intermittent Flow Suzuki Coupling System with Associated Downstream Operations
OptiMax used as MSMPR reaction vessels in continuous crystallization
The authors report the development of a system to enable a fully automated intermittent flow liquid−liquid Suzuki coupling, as well as handle batch metal treatment and continuous crystallization. With respect to the continuous crystallization, OptiMax reactors were used in series as Multistage Mixed Suspension and Mixed Product Removal (MSMPR) vessels driving the ambient temperature antisolvent crystallization.
These MSMPR vessels act as CSTRs that produce and transfer a slurry containing crystals of the product. The authors report that the nominal residence time in the crystallizers was calculated by the fill volume of the crystallizers divided by the total flow rate of incoming feeds. PAT, including ParticleTrack with FBRM and attenuated total reflectance (ATR), was used in measuring the continuous crystallization.
Cole, K. P., Campbell, B. M., Forst, M. B., McClary Groh, J., Hess, M., Johnson, M. D., Miller, R. D., Mitchell, D., Polster, C. S., Reizman, B. J., & Rosemeyer, M. (2016). An Automated Intermittent Flow Approach to Continuous Suzuki Coupling. Organic Process Research & Development, 20(4), 820–830. https://doi.org/10.1021/acs.oprd.6b00030
PFR-CSTR Cascade for Continuous Reactive Crystallization
ReactIR and ParticleTrack provide PAT information and feedback
The authors report the development of a combined PFR-CSTR cascade flow reactor system that incorporated inline FTIR and FBRM sensors as process analytical technology. This system was used to investigate several continuous reactive crystallizations, determining crystal morphology, crystal size distribution, reaction and crystallization yields and supersaturation levels. Residence time distribution (RTD) for the PFR, CSTR cascade and PFR-CSTR cascade were measured and showed that the combined PFR-CSTR cascade had a slightly longer RTD than that of the CSTR cascade alone. For the reactive crystallization, a higher yield was obtained for the PFR-CSTR cascade system as a result of the PFR’s narrower RTD, minimizing both unreacted material and impurity formation.
ReactIR and ParticleTrack probes measured the reactant concentration and crystal chord length during the reactive crystallization process. The reactant concentrations in the mother liquor measured by ReactIR were in good agreement with HPLC results (prediction error < 0.17 %). ParticleTrack measurements revealed a relatively stable chord length of ~ 150 µm.
Hu, C., Shores, B. T., Derech, R. A., Testa, C. J., Hermant, P., Wu, W., Shvedova, K., Ramnath, A., Al Ismaili, L. Q., Su, Q., Sayin, R., Born, S. C., Takizawa, B., O’Connor, T. F., Yang, X., Ramanujam, S., & Mascia, S. (2020). Continuous reactive crystallization of an API in PFR-CSTR cascade with in-line PATs. Reaction Chemistry & Engineering, 5(10), 1950–1962. https://doi.org/10.1039/d0re00216j
Related Resources
Citations and References
Continuous Stirred Tank Reactors in Journal Publications
- Glace, M., Wu, W., Kraus, H., Acevedo, D., Roper, T. D., & Mohammad, A. (2023). Development of a continuous synthesis process for carbamazepine using validated in-line Raman spectroscopy and kinetic modelling for disturbance simulation. Reaction Chemistry and Engineering. https://doi.org/10.1039/d2re00476c
- Copelli, S., Petrucci, N. B., Florit, F., & Barozzi, M. (2022). Increasing Safety by Shifting Semi-Batch Polymerizations into Semi-Continuous Production. DOAJ (DOAJ: Directory of Open Access Journals). https://doi.org/10.3303/cet2290101
- Talicska, C. N., O’Connell, E. C., Ward, H. W., Diaz, A., Hardink, M., Foley, D. P., Connolly, D., Girard, K. P., & Ljubicic, T. (2022). Process analytical technology (PAT): applications to flow processes for active pharmaceutical ingredient (API) development. Reaction Chemistry and Engineering, 7(6), 1419–1428. https://doi.org/10.1039/d2re00004k
- Muir, R., G, B. J., Pearsall, A., Jorgensen, M. J., Sims, B., Yonoski, K., Mehta, N., & Salan, J. S. (2021). Development of a Safe Continuous Process to Sodium Nitrotetrazolate via Solid Phase “Catch and Release.” Organic Process Research & Development, 25(8), 1882–1888. https://doi.org/10.1021/acs.oprd.1c00129
- Ahmed, B., Brown, C., McGlone, T., Bowering, D., Sefcik, J., & Florence, A. J. (2019). Engineering of acetaminophen particle attributes using a wet milling crystallisation platform. International Journal of Pharmaceutics, 554, 201–211. https://doi.org/10.1016/j.ijpharm.2018.10.073
- Glace, A. M., Cohen, B. J., Dixon, D. D., Beutner, G. L., Vanyo, D., Akpinar, F., Rosso, V. W., Fraunhoffer, K. J., DelMonte, A. J., Santana, E., Wilbert, C., Gallo, F., & Bartels, W. (2020). Safe Scale-up of an Oxygen-Releasing Cleavage of Evans Oxazolidinone with Hydrogen Peroxide. Organic Process Research & Development, 24(2), 172–182. https://doi.org/10.1021/acs.oprd.9b00462
- Hu, C., Shores, B. T., Derech, R. A., Testa, C. J., Hermant, P., Wu, W., Shvedova, K., Ramnath, A., Ismaili, L. Q. A., Su, Q., Sayin, R., Born, S. C., Takizawa, B., O’Connor, T. G., Yang, X., Ramanujam, S., & Mascia, S. (2020). Continuous reactive crystallization of an API in PFR-CSTR cascade with in-line PATs. Reaction Chemistry and Engineering, 5(10), 1950–1962. https://doi.org/10.1039/d0re00216j
- Copelli, S., Barozzi, M., Petrucci, N., & Moreno, V. C. (2019). Modeling and process optimization of a full-scale emulsion polymerization reactor. Chemical Engineering Journal, 358, 1410–1420. https://doi.org/10.1016/j.cej.2018.10.055
- Feng, R., Ramchandani, S., Salih, N. M., Lim, X. Y., Tan, S., Lee, L. S., Teoh, S. S., Sharratt, P. N., & Boodhoo, K. (2019). Process Intensification Strategies and Sustainability Analysis for Amidation Processing in the Pharmaceutical Industry. Industrial & Engineering Chemistry Research, 58(11), 4656–4666. https://doi.org/10.1021/acs.iecr.8b04063
- Wernik, M., Poechlauer, P., Schmoelzer, C., Dallinger, D., & Kappe, C. O. (2019). Design and Optimization of a Continuous Stirred Tank Reactor Cascade for Membrane-Based Diazomethane Production: Synthesis of α-Chloroketones. Organic Process Research & Development, 23(7), 1359–1368. https://doi.org/10.1021/acs.oprd.9b00115
- Agnew, L. R., McGlone, T., Wheatcroft, H. P., Robertson, A., Parsons, A. R., & Wilson, C. C. (2017). Continuous Crystallization of Paracetamol (Acetaminophen) Form II: Selective Access to a Metastable Solid Form. Crystal Growth & Design, 17(5), 2418–2427. https://doi.org/10.1021/acs.cgd.6b01831
- Guinand, C. I., Dabros, M., Meyer, T., & Stoessel, F. (2017). Reactor dynamics investigation based on calorimetric data. Canadian Journal of Chemical Engineering. https://doi.org/10.1002/cjce.22700
- Yang, X., Acevedo, D., Mohammad, A., Pavurala, N., Wu, H., Brayton, A. L., Shaw, R., Goldman, M. J., He, F., Li, S., Fisher, R. N., O’Connor, T. G., & Cruz, C. N. (2017). Risk Considerations on Developing a Continuous Crystallization System for Carbamazepine. Organic Process Research & Development, 21(7), 1021–1033. https://doi.org/10.1021/acs.oprd.7b00130
- Cole, K. D., Campbell, B. A., Forst, M. B., Groh, J. M., Hess, M., Johnson, M. H., Miller, R. A., Mitchell, D. L., Polster, C. S., Reizman, B. J., & Rosemeyer, M. (2016). An Automated Intermittent Flow Approach to Continuous Suzuki Coupling. Organic Process Research & Development, 20(4), 820–830. https://doi.org/10.1021/acs.oprd.6b00030
- Yang, Y., Song, L., & Nagy, Z. K. (2015). Automated Direct Nucleation Control in Continuous Mixed Suspension Mixed Product Removal Cooling Crystallization. Crystal Growth & Design, 15(12), 5839–5848. https://doi.org/10.1021/acs.cgd.5b01219
- Rudniak, L., Machniewski, P., Milewska, A., & Molga, E. (2004). CFD modelling of stirred tank chemical reactors: homogeneous and heterogeneous reaction systems. Chemical Engineering Science, 59(22–23), 5233–5239. https://doi.org/10.1016/j.ces.2004.09.014
FAQs
FAQs
What is a CSTR? How does a CSTR work?
A continuous stirred tank reactor (CSTR) is a container used for chemical reactions. It allows the substances needed for the reaction to flow in, while the products flow out at the same time. This makes it a great tool for making chemicals continuously. The CSTR reactor mixes the substances well and works consistently under steady conditions. Typically, the mixture that comes out is the same as what's inside, which depends on how long the substances are in the container and how fast the reaction occurs.
In certain cases, when a reaction is too slow or two different liquids are present requiring a high agitation rate, several CSTRs can be connected together to create a cascade. A CSTR assumes ideal backmixing, which is the opposite of a plug flow reactor (PFR).
Is a CSTR a batch reactor?
No, a CSTR (Continuous Stirred Tank Reactor) is not a batch reactor. The main difference between a CSTR and a batch reactor is that a CSTR is a continuous flow reactor where reactants are continuously fed into the reactor and products are continuously removed, while in a batch reactor, a fixed amount of reactants are added to the reactor and allowed to react until the reaction is complete before the products are removed.
In a CSTR, the reactants are continuously mixed using an agitator or stirrer, which ensures that the reaction mixture is homogenous and well-mixed.
CSTRs are often used in large-scale industrial processes where a continuous supply of reactants is required to meet production demands. Batch reactors, on the other hand, are more commonly used in laboratory-scale experiments, where smaller quantities of reactants are required for testing and analysis and in the production of smaller volume pharmaceuticals, agrochemicals and speciality chemicals.
What is the difference between a CSTR reactor and PFR?
PFR (Plug Flow Reactor) and CSTR (Continuous Stirred Tank Reactor) are two common types of chemical reactors used in industrial and laboratory settings. The main differences between these two reactors are the way they operate and their applications.
- PFR operates by passing reactants through a long tube or channel, where they mix and react as they move through the reactor. In a PFR, the reaction conditions, such as temperature and pressure, should be precisely controlled along the length of the tube. The product stream from a PFR is continuous, and the conversion rate of reactants is typically high. PFRs are often used for large-scale, continuous production of chemicals and petrochemicals.
- CSTR is a well-mixed reactor that continuously stirs reactants in a tank or vessel. In a CSTR, the reaction conditions are uniform throughout the reactor, and the reaction rate is determined by the flow rate of reactants into and out of the tank. CSTRs are commonly used for homogeneous and heterogeneous reactions that require a high degree of mixing and a relatively short residence time.
Overall, the choice between a PFR and CSTR depends on the specific reaction being carried out and the desired production outcome. High quality laboratory data are invaluable for reaction characterization and process modeling can be used to aid reactor selection. Learn more about CSTR vs PFR.
What are the benefits of CSTR over PFR?
Whether continuous flow (CSTR) or PFR (plug flow) is better for a particular application depends on the specific reaction being carried out and the desired outcome. However, in general, CSTRs are often preferred over PFRs for several reasons:
- Good mixing: CSTRs provide good mixing of reactants, especially slurries, which helps to maintain a uniform reaction rate and prevent localized hot spots or dead zones. In contrast, PFRs can sometimes lead to gradients in temperature, concentration, or flow rate, which can affect reaction efficiency.
- Flexibility: CSTRs are highly flexible and can be easily adapted to different reaction conditions or volumes. For example, the residence time can be easily adjusted by changing the flow rate, and the reactor can be scaled up or down depending on the production needs.
- Reduced reaction time: CSTRs can often achieve a high conversion rate in a relatively short residence time since the reactants are well mixed and the reaction conditions are uniform. This can lead to faster reaction times and higher production rates.
- Lower costs: CSTRs are generally simpler and less expensive to construct and operate than PFRs since they do not require long, specialized tubing and associated equipment.
Overall, the choice between a CSTR and a PFR depends on the specific needs of the reaction being carried out, and both reactors have their advantages and disadvantages. However, CSTRs are often favored for their flexibility, good mixing, and ability to achieve high conversion rates in a short residence time.