Reaction Calorimeters

Process Safety Design and Scale-up

A reaction calorimeter is a tool used by scientists in chemical and pharmaceutical development to measure the amount of energy released or absorbed by a chemical or physical reaction.

It typically consists of a stirred tank reactor of variable size in which the temperature of the reaction mass is monitored and precisely controlled, together with all relevant critical process parameters.

Reaction calorimeters allow the investigation of chemical processes under process-like conditions, providing a full set of information about the scalability and safety of the process.

Depending on the stage of development, additional information might also be relevant. Thus, complementary data (e.g. analytical data from Infrared, Raman, HPLC, or similar) may be collected and integrated with the heat flow data.

Reaction Calorimeters for Screening, Process Development, and Process Safety Studies

RC1mx HFCal™

Ensure Safety by Design

World-leading reaction calorimeter for process safety and scale-up.

Temperature Range: -70 °C – 300 °C
Operating Volume: 100 mL – 22 L

Optimax HFCal™

Detect Non-Scalable Conditions

For fast and efficient safety studies for process characterization and scale-up.

Temperature Range: -40 °C – 180 °C
Operating Volume: 150 mL – 1,000 mL

EasyMax 402 HFCal™

Calorimetry for Safety Screening

Designed for fast and efficient safety screening and characterization of chemical processes early in development.

Temperature Range: -40 °C – 180 °C
Operating Volume: 80 mL – 400 mL

EasyMax 102 HFCal™

Calorimetry for Safety Screening

Designed for fast and efficient safety screening and characterization of chemical reactions at small scale.

Temperature Range: -40 °C – 180 °C
Operating Volume: 40 mL – 100 mL

EasyMax 102 LT HFCal™

Developed for Low Temperatures

Facilitates low temperatures at the push of a button. Special purging of the reactor zone prevents icing.

Temperature Range: -90 °C – 80 °C
Operating Volume: 40 mL – 100 mL

The RC1mx™ reaction calorimeter is the industry “Gold-Standard” for measuring heat profiles, chemical conversion, and heat transfer under process-like conditions. RC1mx provides a modern solution with a high-performance thermostat as the centerpiece. RC1mx allows chemical and safety engineers to optimize processes under safe conditions while determining all critical process parameters and reducing the risk of failure on a large scale.

OptiMax HFCal, EasyMax 402 HFCal, and EasyMax 102 HFCal are smaller-scale heat flow calorimeters that combine the benefits of a synthesis workstation and a reaction calorimeter. These calorimetry instruments are designed for process safety screening and scale-up and provide relevant reaction information early in the development process.

Real-Time Reaction Calorimetry Data

The development and optimization of chemical processes require the determination of a variety of different types of information in order to make the best decisions. It is common to collect analytical data, such as Infrared (IR), Raman, particle size distribution, or concentration online and in real-time to create kinetic models and gain mechanistic unterstanding. Collecting heat release data in real time is absolutely necessary to design safe and sustainable chemical processes.

Reactor systems that enable the scanning of reactions for heat release in real-time provide instantaneous feedback on the progress of the reaction and allow users to immediately take corrective actions. Online heat data in real time is often used to control the process by adjusting critical process parameters, such as the addition rate of reactants, controlling the pressure, the stirring speed, or any other process parameter.

With the RTCal™ reactor, the researcher uses a PAT (process analytical technology) tool that allows tracking reactions in real time. It delivers valuable heat information about the progress of the reaction without the need for expert knowledge. RTCal™ technology uses heat flux sensors that are built into the reactor, detecting the heat flow across the wall of the reactor.

The measurement of heat data with RTCal™ is independent of the properties or the behavior of the reaction mass. Hence, no calibration procedures need to be run before, during, or after the reaction, which reduces the experiment time substantially.

Safe Processes at Any Scale

METTLER TOLEDO reaction calorimeters enable safety screening from lab to plant scale to ensure safe and robust scale-up. Whenever a process is scaled-up, critical variables that affect the performance or outcome need to be investigated. In some cases, the route chosen is not scalable because of expensive or scarce starting materials, conditions that are difficult to control in large vessels, or potential safety hazards and thus, needs to be modified.

This requires the investigation of scale-dependent variables, such as dosing rates, mixing, or mass transfer. However, one of the key pieces of information to move a process into manufacturing safely is the understanding of the total heat released, the heat release rate, the accumulation of reactant(s) or energy as well as the stability of the reaction mass and the individual components.

Reaction calorimetry studies provide evidence of the critical process parameters and their impact on the process, the manufacturability, the yield, and the quality of the product or intermediate.

Since chemical reactions are influenced by several parameters such as concentration, addition rate, temperature, solvent, catalyst and pH value, the seamless integration of online analytics or automated sampling tools into the reaction calorimeter increases the value of the study tremendously.

Data-rich experiments comprising both calorimetry and analytical information effectively support today's needs for developing safe and robust processes fast and transferring them from lab to plant effectively.

Chemistries at Subambient Temperature

LowTemp (LT) reactor models expand the temperature design space down to -90°C for the discovery of new synthetic pathways, process optimization, and design of reactions including organometallic metalation and lithiation reactions at sub-ambient conditions.

Unlike traditional equipment with discrete temperatures at 0°C, -21°C (sodium chloride in ice), and -78°C (acetone/dry ice), our LowTemp reactors precisely control experimental conditions along a broad temperature range – even when unattended.

Combine the EasyMax LT with the HFCal upgrade kit to cover chemistries at the most extreme temperatures.

Calorimetry in Process Safety Screening

Bringing new chemical or pharmaceutical entities to market successfully requires innovative ideas, creative researchers, and modern tools that support an effective development workflow. Reaction calorimeters enable:

Experiments to be carried out at small scales due to a lack of material
Precise data collection
Data application to statistical approaches (e.g. Design of Experiments (DoE) Studies)
Confidence to identify scalability and safety issues at an early development stage

Comprehensive Process Safety Studies

Reaction calorimeters provide reliable data to calculate the relevant safety parameters and to understand potential risks. To improve safety considerations, reaction calorimeters are often paired with software to:

Automatically convert reaction calorimetry data into safety information
Analyze the thermal risk (e.g. thermal accumulation, ΔTadiabatic, MTSR)
Auto-generate and share reports

Accelerate Process Development with Dynochem

Dynochem chemical reaction modeling software ensures effective mixing and heat transfer when scaling up reactions. Easily and quickly compare lab, pilot, and production scale reactors, and find the appropriate mixing parameters to safely speed reactor-to-reactor process transfer. With data provided by reaction calorimetry and Dynochem modeling, quickly ensure chemical process safety and process performance across scales.

Reaction Calorimetry FAQs

What is reaction calorimetry?

Reaction calorimetry measures the heat released from a chemical reaction or physical process and provides the fundamentals of the thermochemistry and kinetics of a reaction.

The information obtained is essential to describe the heat release of a chemical reaction over time, and to safely transfer it from lab to plant.

Reaction calorimetry uncovers unexpected behavior and makes any scalability issues visible and quantifiable. It also helps to identify issues related to heat and mass transfer or mixing, and allows the determination of the correct temperature, stirring, or dosing profile of a given reaction or process. The information obtained is subsequently used to evaluate a process's risk, scalability, and criticality.

Reaction calorimetry data is used to characterize, optimize, and understand process parameters in a controlled, accurate, and reproducible environment, enabling safe scale-up and transfer into manufacturing.

What is heat flow calorimetry?

Heat flow calorimetry is the simplest and most robust method for determining the heat released by a chemical reaction or physical process. It is supported by all METTLER TOLEDO reaction calorimetry workstations. Heat flow calorimetry is highly sensitive and applicable under most conditions, and it offers excellent repeatability.

The heat flow calorimetry principle is based on measuring the temperature difference across the reactor wall, which is then converted into a heat flow by measuring its heat transfer coefficient.

The heat transfer coefficient depends on the type of chemistry, reaction conditions, and the reactor material and is determined using a reference electrical heater.

To get real and accurate data, each workstation and reactor is provided with a Thermal Analysis (Ta) model that corrects the heat flow through the reactor walls, considering the thermal conductivity and thickness of the reactor wall, the thermal resistance of the reaction mass film, and the thermal resistance of the oil film.

The method of heat flow calorimetry is applicable on both small and large scales and is the basis for all chemical process development projects, process scale-up, and chemical process safety investigations.

What is the value of reaction calorimetry?

Reaction calorimeters allow the efficient and safe development of processes at scale.

As a reaction is scaled from lab to plant, scalability problems may suddenly emerge for various reasons. In the worst case, unidentified reaction risks may lead to a runaway reaction followed by an explosion. The causes of thermal incidents are often attributed to:

Lack of understanding of the chemistry or the thermochemistry of a process
Inability to remove heat
Bad or poorly understood mixing behavior
Human factors

Incidents can be avoided by determining the relevant data at lab scale. The lab work is performed under process-like conditions using reaction calorimeters so that the results can be directly applied to larger-scale operations.

Reaction calorimetry provides a high level of process understanding so that the necessary procedures can be performed routinely, robustly, and to the required quality standards.

How can you obtain accurate and precise calorimetric data under any conditions?

Accurate and precise heat flow data is essential for transitioning from lab to plant. A high-performance heating and cooling system combined with a sensitive temperature measurement and control system is a prerequisite to obtaining accurate and precise heat information about a chemical process. This includes details about the heat of the reaction, the total heat flow balance, the mass and heat transfer, and the specific heat of the reaction mass.

The total heat flow balance of a chemical process itself includes a variety of thermal effects, such as the accumulation of heat, heat exchange due to reactant or solvent additions, heat due to changing viscosity, heat loss, etc.

For reactions that are run under changing temperature conditions, heat accumulation becomes an important factor in the calculation of the heat of the reaction (heat released as a function of time). In this case the correction from isothermal to non-isothermal temperature control is essential and the Thermal Analysis (Ta) model plays an extremely important role.

METTLER TOLEDO reaction calorimeters and iControl software suite use sophisticated calculation algorithms. These take into account the dynamic behavior of the reactor wall, the heat capacities of the vessel, and the reactor inserts – providing calorimetric data of maximum accuracy and precision.

What is heat of reaction?

The heat of reaction, or reaction enthalpy, is the energy that is released or absorbed during a chemical reaction. When reactants are transformed into products, it describes how the energy content changes. While there are endothermic (heat absorbing) and exothermic (heat releasing) reactions, the majority of reactions carried out in the chemical and pharmaceutical sectors are exothermic. The heat of reaction is one of the thermodynamic characteristics that is utilized in chemical research, scale-up, and safety to scale processes from the lab scale to production, among other things.

Learn more about heat of reaction and reaction enthalpy.

Can I connect my reaction calorimeter to third party accessories?

Yes! The Easy Control Box (ECB) accessory (purchased separately) extends your reaction calorimeter automated control and data capture of third-party devices, including sensors, dosing, and sampling solutions.

ECB provides dosing control capabilities and easily connects commercially available pumps and balances for automated pre-programmed gravimetric or volumetric dosing. The accessory has plug-and-play measure functionality with SmartConnect Technology Sensors. Control elements are automatically recognized making the reactor system configuration a simple task.

Learn more about Easy Control Box (ECB).

Reaction Calorimetry Resources

Gelinski, E. K., Sheibat–Othman, N., & McKenna, T. F. L. (2023). Mass transfer in emulsion polymerization: An experimental and modelling study. Canadian Journal of Chemical Engineering/˜the œCanadian Journal of Chemical Engineering, 102(2), 532–547. https://doi.org/10.1002/cjce.25120
Nandi, S., Padrela, L., Tajber, L., & Collas, A. (2023). Nucleation kinetics-based solvent selection for the liquid antisolvent crystallization of a lipophilic intermediate. Journal of Molecular Liquids, 375, 121306. https://doi.org/10.1016/j.molliq.2023.121306
Quan, Y., Parker, T., Hua, Y., Jeong, H., & Wang, Q. (2023). Process elucidation and hazard analysis of the Metal–Organic Framework Scale-Up Synthesis: A case study of ZIF-8. Industrial & Engineering Chemistry Research, 62(12), 5035–5041. https://doi.org/10.1021/acs.iecr.2c04570
Yang, Q., Canturk, B., Gray, K., McCusker, E., Sheng, M., & Li, F. (2018). Evaluation of Potential Safety Hazards Associated with the Suzuki–Miyaura Cross-Coupling of Aryl Bromides with Vinylboron Species. Organic Process Research & Development, 22(3), 351–359. https://doi.org/10.1021/acs.oprd.8b00001
Monteiro, A. M., & Flanagan, R. C. (2017). Process Safety Considerations for the Use of 1 M Borane Tetrahydrofuran Complex Under General Purpose Plant Conditions. Organic Process Research & Development, 21(2), 241–246. https://doi.org/10.1021/acs.oprd.6b00407
Hua, M., Qi, M., Pan, X., Yu, W., Zhang, L., & Jiang, J. (2017). Inherently safer design for synthesis of 3-methylpyridine-N-oxide. Process Safety Progress, 37(3), 355–361. https://doi.org/10.1002/prs.11952
Jyotsna, G. K., Srikanth, S., Ratnaparkhi, V., Rakeshwar, B. (2017). Reaction calorimetry as a tool for thermal risk assessment and improvement of safe scalable chemical processes. Inorg Chem Ind J.,12(1),110.
Pečar, D., & Goršek, A. (2015). Saponification reaction system: a detailed mass transfer coefficient determination. Acta Chimica Slovenica, 62(1). https://doi.org/10.17344/acsi.2014.1110
Wang, J., Huang, Y., Wilhite, B. A., Papadaki, M., & Mannan, M. S. (2018). Toward the Identification of Intensified Reaction Conditions Using Response Surface Methodology: A Case Study on 3-Methylpyridine N-Oxide Synthesis. Industrial & Engineering Chemistry Research, 58(15), 6093–6104. https://doi.org/10.1021/acs.iecr.8b03773
Lakshminarasimhan, T. (2014). Predicting 24 and 8 h Adiabatic Decomposition Temperature for Low Temperature Reactions by Kinetic Fitting of Nonisothermal Heat Data from Reaction Calorimeter (RC1e). Organic Process Research & Development, 18(2), 315–320. https://doi.org/10.1021/op400301f
Mitchell, C. W., Strawser, J. D., Gottlieb, A., Millonig, M. H., Hicks, F. A., & Papageorgiou, C. D. (2014). Development of a Modeling-Based Strategy for the Safe and Effective Scale-up of Highly Energetic Hydrogenation Reactions. Organic Process Research & Development, 18(12), 1828–1835. https://doi.org/10.1021/op500207r

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