XRCC specializes in scaling-up chemistries from the lab bench to the pilot plant, and is committed to process safety at each and every stage. Developing and transferring new chemical syntheses from the laboratory to manufacturing scale requires a thorough understanding of the chemical route and reaction thermochemistry. XRCC uses comprehensive reaction calorimetry to assess potential hazards starting from the earliest stages of scale-up, saving our clients time and money in the developmental pipeline.
The Importance of Understanding Reaction Thermochemistry for New Processes
New syntheses often begin as batch or semi-batch processes, with the main hazards a result of the reactivity and toxicity of the materials used. Although the toxicity of reagents cannot be directly influenced without making changes to the synthetic procedure itself, the reactivity of a process can be controlled using a smart engineering design, provided key process information is known. XRCC engineers begin each project by assessing potential hazards of the chemical processes involved. For exothermic systems this information can be condensed into the following six questions:
1. Can the process temperature be controlled by the cooling system?
2. What temperature can be attained after runaway of the desired reaction?
3. What temperature can be attained after runaway of secondary decomposition reactions?
4. At what moment does a cooling failure have the largest impact?
5. How fast is the runaway of the desired reaction?
6. How fast is the runaway of secondary decomposition reactions?
These questions provide guidance on forming a runaway scenario for risk assessment (Figure 1). For a given process, this information helps identify thermal hazards that can arise due to a number of scaling factors. For example, inadequate mixing of chemicals can result in mass transfer limitations whereas, suboptimal temperature and feed profiles can lead to dangerous reactant accumulation.
Failure to address these issues can result in loss of control of the desired reaction, potentially triggering secondary decomposition reactions (thermal runaway). The uncontrolled reactions can result in damage to equipment, serious worker injury, and destructive environmental impact. Correcting these inadequacies late in process development can potentially incur substantial costs to the client. A process will always be more economical if potential issues are evaluated early in the design stage, minimizing the need for specialized equipment and safety features. XRCC is committed to de-risking the scale-up of processes for our clients, and our engineers are involved in every step of the design phase to ensure safe and economical operation.
Determining Reaction Criticality
By examining the runaway scenario presented above (Figure 1), a systematic approach to determine the criticality of a given process can be developed using a few key temperature thresholds. By considering the relative positions of four temperature levels, the hazard potential of a chemical process can be estimated:
• The process temperature (Tp) is the internal temperature of the reaction mass at the time of cooling failure.
• The maximum temperature of synthesis reaction (MTSR) is the highest temperature reached by the reaction mass resulting from accumulated reactants.
• TD24 can be described as the highest temperature at which the thermal stability of the reaction mass is not problematic.
• The maximum temperature due to technical limitations (MTT) is the highest temperature achievable due to limitations on the reaction process. (E.g. boiling point of solvent in open systems, set point of pressure relief valve in closed systems).
This information allows for classification of the process into one of five criticality levels (Figure 2). Based on the criticality level identified, our process engineers can make educated decisions on which reactor geometries are appropriate, which safeguards need to be put in place to ensure inherently safe operation, or whether alternative conditions should be explored to minimize risks.
Process Data Collection and Analysis
To obtain the information required to assess potential reaction hazards, XRCC uses a combination of reaction calorimetry, differential scanning calorimetry, and computer modelling. The techniques enable us to create a more complete process picture and to make educated engineering decisions during scale-up.
Reaction Calorimetry (RC) allows for direct measurement of the reaction heat-flow under conditions which mimic real process conditions. The data obtained from reaction calorimetry experiments allow for determination of heats of reaction, adiabatic temperature rise, MTSR, reactant accumulation, and maximum instantaneous heat generation (Figure 3).
Differential Scanning Calorimetry (DSC) allows for stability evaluation of the reaction mass. Parameters are collected under both isothermal and dynamic temperature profiles to characterize undesired and secondary reactions. From this information the temperature of secondary reaction onset and TD24 can be calculated.
Computer Modelling is a powerful tool used to optimize reaction parameters such as feed rate, temperature profile, and hold times without dedicating a large amount of resources to experimental work. Using parameters obtained from RC, DSC, and known coefficients for XRCC’s process reactors, it is possible to model the vessel temperature profile and product conversion as a function of a number of input parameters. The reagent feed rate, jacket temperature, and hold time are a few parameters which can be optimized using this technique.
Developing a safe manufacturing scale process hinges on the information known on the reaction thermodynamics. XRCC obtains information, evaluates hazards, and designs processes around reaction thermochemistry to optimize cycle time and maximize product yields through the scale-up pipeline.
 F. Stoessel, Planning protection measures against runaway reactions using criticality classes, Process Saf. Environ. Prot. 87 (2009) 105–112.
 R. Gygax, Chemical reaction engineering for safety, Chem. Eng. Sci. 43 (1988) 1759–1771.
Author: Alex Rousina-Webb, Process Engineering Specialist, Xerox Research Centre of Canada