Reaction Calorimeters

Investigations with reaction calorimeters, such as the OptiMax HFCal Heat Flow Calorimeter and the RC1mx Reaction Calorimeter, provide detailed information needed for thorough scale-up and process safety studies. The RC1 is the gold standard in reaction calorimeters.

Assessing safety is a task inherently present early in development. The challenges to developing a safe process can already be observed and addressed during chemical development. Simple tools, such as an EasyMax Chemical Synthesis Reactor or EasyMax HFCal Heat Flow Calorimeter, provide information to allow identification and minimization of the risk of non-scaleable conditions early in development.

Screening at small scale increases productivity in development, can be executed with low quantities of precious raw materials, reduces the amount of waste significantly, and provides information critical to taking go-no-go decisions.

As a reaction is scaled from lab to plant, scalability problems may suddenly emerge for various reasons. The causes of thermal incidents are often attributed to:

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

Incidents can be avoided by determining the relevant data at laboratory scale. Laboratory 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 standard of quality.

Chemical and pharmaceutical industries often use complex chemical processes in which large amounts of energy can be released. Knowing and understanding the potential risks is critical, and a prerequisite for safe manufacturing of chemical and pharmaceutical products.  This includes the understanding of the thermodynamics of the desired reaction, as well as that of a possible undesired reaction.

Using the RC1mx Reaction Calorimeter provides reliable data to calculate the relevant safety parameters of the main reaction with the highest degree of confidence. iC Safety turns experimental data into safety information, combines it with data from the undesired reaction and presents the thermal risk (e.g. thermal accumulation, ΔTadiabatic, MTSR etc) in a concise and easy-to-understand format (e.g. table, runaway and criticality graph). 

EasyMax HFCal and OptiMax HFCal (Heat Flow Calorimeters) combine the benefits of a synthesis workstation and a reaction calorimeter. As small scale reaction calorimeters, they are designed for process safety screening and provide reaction information early in the development process. 

Heat flow calorimetry data can be used to characterize, optimize and understand process parameters in a controlled, accurate and reproducible environment.

The RC1 Reaction Calorimeter is the industry “Gold Standard” for measuring heat profiles, chemical conversion and heat transfer under process-like conditions. The RC1mx Reaction Calorimeter provides a modern solution with a high-performance thermostat as the centerpiece.  The 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.

Bringing new chemical or pharmaceutical entities to market successfully asks for innovative ideas, creative researchers and modern synthesis tools that support an effective development workflow.

Experiments are to be carried out at small scale due to lack of material while the data obtained need to be precise. It is imperative that data applied to statistical approaches, e.g. Design-of-Experiments, but also experiments based on traditional procedures, be trustworthy, allowing the identification of scalability and potential safety issues at an early stage in development. This enables increased productivity in chemical development and also ensures that a process can be carried out safely and economically at large scale.

Chemical process safety and related-applications using reaction calorimeters are referenced in many publications, including:

• Qiang Yang, Belgin Canturk, Kaitlyn Gray, Elizabeth McCusker, Min Sheng, Fangzheng Li; Evaluation of Potential Safety Hazards Associated with the Suzuki−Miyaura Cross-Coupling of Aryl Bromides with Vinylboron Species; Org.ProcessRes.Dev.2018, 22, 351−359
  
  
• Jingyao Wang, Yanyan Huang, Benjamin A. Wilhite, Maria Papadaki, M. Sam Mannan, Toward the Identification of Intensified Reaction Conditions Using Response Surface Methodology: A Case Study on 3‑Methylpyridine N‑Oxide Synthesis, Industrial & Engineering Chemistry Research 2019 58 (15), 6093-6104
  
  
• Thirumalai Lakshminarasimhan, Predicting 24 and 8 h Adiabatic Decomposition Temperature for Low Temperature Reactions by Kinetic Fitting of Nonisothermal Heat Data from Reaction Calorimeter, Org. Process Res. Dev. 2014, 18, 315−320
  
  
• Kamala Jyotsna G, Srikanth S, Ratnaparkhi V, et al. Reaction calorimetry as a tool for thermal risk assessment and improvement of safe scalable chemical processes. Inorg Chem Ind J. 2017;12(1):110
  
  
• Darja Pecar and Andreja Gorsek, Saponification Reaction System: a Detailed Mass Transfer Coefficient Determination, Acta Chim. Slov. 2015, 62, 237–241
  
  
• Christopher W. Mitchell, Josiah D. Strawser, Alex Gottlieb, Michael H. Millonig, Frederick A. Hicks, and Charles D. Papageorgiou, Development of a Modeling-Based Strategy for the Safe and Effective Scale-up of Highly Energetic Hydrogenation Reactions, Org. Process Res. Dev. 2014, 18, 1828−1835
  
  
• Min Hua, Min Qi, Xuhai Pan, Wendi Yu, Lu Zhang, and Juncheng Jianga, Inherently Safer Design for Synthesis of 3-Methylpyridine-N-Oxide, Process Safety Progress, Wiley Online Library (wileyonlinelibrary.com). DOI 10.1002/prs.11952
  
  
• Alexandre M. Monteiro, Roy C. Flanagan, Process Safety Considerations for the Use of 1 M Borane Tetrahydrofuran Complex Under General Purpose Plant Conditions, Org. Process Res. Dev. 2017, 21, 241−246