Recently, I saw a conversation on the LinkedIn Organic Process Research & Development (OPRD) Group that began with the subject: “Precaution during scale-up of a Grignard reaction?”. This discussion regarding the safety of Grignard reactions on scale made me realize how useful old chemical reactions can be, although not necessarily well-understood or controlled.
As of August 12, 2010, the number of comments in this LinkedIn OPRD discussion was 23 – and in only one month. For me, this illustrates the concern many chemists and engineers have regarding the use of a Grignard reaction on a large scale. RC1e reaction calorimetry and ReactIR in situ FTIR spectroscopy – either independently or in combination – are excellent methods to make sure the Grignard reaction will be safe on scale.
Some great papers on the topics from Organic Process Research & Development (OPRD) include:
- Safety Improvements of a Grignard Reaction by Controlling the Reactant Feed, 2006, 10, 1282-1286 and 2005, 9 (3), 365 -371
- Preparation of Grignard Reagents: FTIR and Calorimetric Investigation for Safe Scale-up, 1999, 3(5), 319-329
- Activation of Mg Metal for Safe Formation of Grignard Reagents on Plant Scale, 2002, 6, 906-910
Simon Rea gave an interesting presentation on this topic as well – Identifying Non-Scalable Reaction Conditions at Small Scale – which is now available on-demand.