Heat of Reaction

For quite some time, safety considerations have become an essential component of chemical process development, and safety concepts are routinely developed while designing the pilot or large scale process. Industrial associations and federal authorities, such as CSB, OSHA (US), HSE (UK), EU-OSHA, EPSC (EU) or IPE and the State Administration of Work Safety (SAWS) in China, require chemical and pharmaceutical industries to comply with regulations that assure safe production. The directives provided focus on avoiding incidents and accidents in the chemical and pharmaceutical industries.

Risk assessment requires key chemical data that describes the properties of the substances, but also information about the process itself. Among other thermal information, the heat of reaction is an essential parameter that can be used to derive information related to safe processes and to build up process safety knowledge. Building process safety knowledge also means understanding both the desired and possible undesired reactions. While the undesired reaction is primarily concerned with identifying possible side or consecutive reactions that may be followed by a runaway reaction, the investigation of the desired reaction demonstrates how the reaction behaves under normal operating conditions.

The accumulation of starting material, the heat of reaction, the enthalpy of reaction and the specific heat are some of the key parameters necessary to create cooling failure scenarios of the desired reaction. However, more advanced studies, such as the evaluation of worst case scenarios, criticality class or the criticality matrix, use the information from the heat of reaction to the same extent.

The heat of reaction can be calculated based on the standard heat of formation of all reactants involved. However, it is usually determined by measuring the heat production over time using a reaction calorimeter, such as a heat flow calorimeter.

The determination of the heat of reaction requires the knowledge of the overall heat flow balance, including the heat flow through the reactor wall, the amount of heat that is exchanged during dosing of reactants or solvents and the heat that is accumulated due to a temperature increase or decrease.

While the heat release rate and the heat of reaction provide information how the heat is released in function of time, the heat of reaction enthalpy is obtained by integrating the heat of reaction trend between start and end of the reaction. As all of the individual heat flow terms are relevant for the overall heat balance, care has to be taken to determine them as accurately as possible.

For more than 30 years, the RC1 has been the gold standard in reaction calorimetry; RC1 is an instrument you can trust. The RC1mx builds on its predecessors by adding a level of convenience for faster development of better optimized, more robust and economically viable processes.

• Understand Your Process
  Determine thermodynamic data quickly and precisely under isothermal or non-isothermal conditions.
  
• Heat Flow Calorimetry – Simply Reliable
  Immune and robust against external influence, heat flow calorimetry allows to accurately and precisely measure the evolution of heat under process conditions.
  
• Measure the True Heat of Reaction
  Measuring the true heat of reaction is the basis to understanding the progress of chemical reactions, their kinetics and its hazard potential.

The thermal conversion is relevant information for chemical process development, and describes the relationship between the partial heat of reaction as a function of time and the total heat of reaction. The calculation of the thermal conversion is based solely on the heat released during the reaction as opposed to the chemical conversion, which is based on the chemical conversion from reactants into products.

While the thermal conversion at the end of the reaction is always 100 %, the chemical conversion may be lower, and varies depending on the choice of process parameters. It is indeed the goal of chemical development to achieve the highest possible conversion of reactants, resulting in the highest yield possible.

Reaction calorimetry combined with real-time analysis, such as in-situ FTIR spectroscopy, is an ideal method to study the progress of a chemical reaction, the conversion of reactants, the formation of products, by-products and intermediates, while measuring thermodynamic information, such as the heat of reaction, the heat flow, the specific heat or the heat transfer at the same time.

Thanks to information obtained from the RC1 (e.g. heat of reaction, heat capacity and the heat production rate), an established but challenging process was optimized and implemented at large scale within a very short time. The optimization resulted in savings of approximately $70,000 because no pilot stage was required. In addition, annual savings of $50,000 on production costs could be realized due to the less expensive equipment and the larger batch size.

Both steps of an indole synthesis, the phenylhydrazone synthesis followed by a Fischer ring closure, were investigated in an RC1 reaction calorimeter.

The main focus of the investigation was on the heat release rate, the heat of reaction and the heat transfer, as well as the impact of the reaction temperature, and at a later stage, the dosing rate on the information above. Based on the experimental data, the temperature and dosing regime, as well as the time and the cooling, performance required for the operations in the plant reactor could be estimated. The fact that the existing process could be modified to become virtually dosing-controlled also improved the safety at manufacturing scale, which substantially eliminated the need for expensive safety measures.

Use Dynochem modeling to ensure effective mixing and heat transfer when scaling-up reactions. Dynochem makes it easy to 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. 

Below is a selection of publications that discuss the heat of reaction or reaction enthalpy.

• Agosti, A., Bertolini, G., Bruno, G., Lautz, C., Glarner, T., & Deichtmann, W. (2017). Handling Hydrogen Peroxide Oxidations on a Large Scale: Synthesis of 5-Bromo-2-nitropyridine. Organic Process Research & Development, 21(3), 451–459. https://doi.org/10.1021/acs.oprd.6b00433
• Changi, S. M., & Wong, S. W. (2016). Kinetics Model for Designing Grignard Reactions in Batch or Flow Operations. Organic Process Research & Development, 20(2), 525–539. https://doi.org/10.1021/acs.oprd.5b00281
• Glotz, G., Knoechel, D. J., Podmore, P., Gruber-Woelfler, H., & Kappe, C. O. (2017). Reaction Calorimetry in Microreactor Environments—Measuring Heat of Reaction by Isothermal Heat Flux Calorimetry. Organic Process Research & Development, 21(5), 763–770. https://doi.org/10.1021/acs.oprd.7b00092
• 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
• 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