Alessandro Agosti obtained his MSc in Industrial Organic Chemistry at the University of Milan and his PhD at the University of Berne under the supervision of Prof. Philippe Renaud. His research involved the discovery of new synthetic methodologies for the construction of aza-spirocycles, a structural motif of naturally occurring alkaloids. Afterwards, he conducted postdoctoral research in the group of Prof. Timothy Jamison at the Massachusetts Institute of Technology (MIT). He then had a second postdoctoral stay at the Laboratory for Process Research in Switzerland where he began applying organic chemistry for the development of synthetic processes of pharmaceutical relevant molecules. In 2011, he started his industrial career in INFA Group (now OLON) on the outskirts of Milan (Italy) as a Process Development Scientist, being involved in the design, optimization and industrialization of complex chemical processes for the production of advanced intermediates and APIs. He is currently the Head of Process Safety Laboratory at OLON Spa.
Continuous Safety Improvements to Avoid Runaway Reactions
Reactions with hazardous chemistries, such as cyanides, bromine and sodium metal, are not uncommon, and need special attention when scaling from small to large scale. Careful investigation and continual safety improvements are particularly important for processes that include highly reactive or hazardous chemistries.
Alessandro Agosti of Olon Spa discusses the risk assessment approach for a transformation of morpholine with dichlorothiadiazole (a high-temperature process) and how to ensure safety at large scale. The approach uses the risk assessment methodology based on the cooling failure scenario from Prof. Stoessel – allowing scientists to estimate the criticality of a reaction. In order to obtain the full picture of the process, all possible reaction pathways were investigated. This includes the desired main reaction, but also possible undesired reactions, as all of these contribute to the heat generation and potentially may lead to critical or even runaway situations.
In the studies, reaction calorimetry was used to investigate the desired reaction while differential scanning calorimetry (DSC) was used to collect the safety data of the starting material, the intermediates, the final products and the reaction mixture. Based on these, the decomposition kinetics and subsequently the Time-to-Maximum-Rate (TMR) of the decomposition reaction were evaluated.
Combining the information of the desired reaction with the ones of the undesired reaction leads to the criticality class describing the reaction as highly critical. To study the consequences of the decomposition reaction additional experiments were executed using an adiabatic calorimeter. With this additional information at hand, a risk matrix (probability vs. consequence) was created determining the level of risk as unacceptable.
Consequently, a number of process parameters were modified to:
- Improve the temperature and reaction control
- Limit formation of unstable components
- Reduce the overall criticality
View the webinar to see how modifications led to a safer, but also, high-quality process.