Client Background
The client is a Pharmaceutical CDMO brand. This brand was working to scale up a new reaction process to produce Grignard reagents for further reactions.
Client Problem
The chemistry is well established in the literature and is known to be a difficult reaction to initiate.
Close communication between R&D teams and our laboratory staff agreed on a desired method and reagent dosage regime with greater reliability.
Client Objectives
Understand and quantify heat evolved, reaction rates and reaction initiation, and also to identify any thermal decomposition risks of reaction mixtures and products.
This was all to fully assess the intrinsic risks of the reaction process to support scale up from laboratory scale to plant.
Testing Overview – What is Reaction Calorimetry?
Reaction Calorimetry testing is performed to assist in process development or scale up of new chemical reactions for industrial chemical manufacture.
The testing provides information on reaction kinetics, heat evolution, gas generation, reactant accumulation and more, which all feeds into the proper design of processes and helps to optimise syntheses.
The testing provides information on reaction kinetics, heat evolution, gas generation, reactant accumulation and more, which all feeds into the proper design of processes and helps to optimise syntheses.
Strategy
The reaction was studied with the presence of a reaction initiator reagent after previous unsuccessful attempts without the initiator, to match the clients experience at laboratory scale trials.
The desired Grignard formation and subsequent quench steps were studied using the Power Compensated Calorimetry mode, which quantified the reaction heat against the calibrated internal heater. Reaction Calorimetry was supported by thermal screening studies with Differential Scanning Calorimetry and Carius tube, to assess hazard criticality of the process as a whole.
