(714a) Process Safety Evaluation and Scale-up Resorting to Mechanistic Modelling for Exothermic and Gas Release Reactions

The present work regards all the steps taken during the development and scale-up of an exothermic (Stoessel criticality class 5) and gas releasing (> 1.7m3/kg) reaction, while evaluating the potential impact of the control strategy on the large-scale process conditions/outcome.

Even tough the main reaction is exothermic, the most part of the heat generated throughout the process comes from the decomposition of the reagent in the solvent, with strong gas release. This was determined by performing a blank run without starting material, where it was observed that similar heat and gas releasing profiles were obtained between normal process and blank run. After this finding, it was relatively straight-forward to propose a mechanism that could represent the reaction data such as yield, heat output and gas release, from routine lab experiments and calorimetry studies data.

The following step was to determine the heat transfer capability of the large-scale reactor by performing heating/cooling cycles with the same solvent of the reaction and collecting jacket and reactor temperatures throughout the cycles. Afterwards, it was possible to simulate what-if scenarios at large scale and calculate the accumulated heat through time and determine the best conditions in terms of jacket temperature and feeding duration to optimize yield, productivity and avoiding temperature spikes. We also estimated what would be the outcome in case of cooling failure scenario, which helped to understand and design the safe guards strategy that included how long the cooling could be on hold between changing from the regular heat transfer fluid to liquid nitrogen.

The large-scale campaign was composed of 3 batches of >50 kg (54.4, 54.2 and 94.7 kg) and without any impact on safety (for people and process) nor yield.