- Pilot-plant scale
9. The pilot plant results were identical to those in the lab.
10. However, on plant-scale, the Grignard reaction could not be initiated.
11. Back in the lab, it was demonstrated that small quantities of acetone are the real cause of this Grignard initiation problem.
12. Acetone was a cleaning solvent, frequently used to dry reactors, condensers and piping. Usually final traces of this solvent could be removed by applying vacuum on various equipment sections.
13. After the make-up of magnesium and THF, a certain quantity of Grignard solution of the previous batch was added to destroy remaining acetone...I can only imagine the irritation of the chemists upon learning of this stumbling block.
Grignard initiation on plant scale can be tricky and potentially quite dangerous (in terms of adding a bunch of halide and magnesium together that might react all-at-once and spray hot flammable solvent out of the rupture disk.) I've heard of SOPs where a verifiable initiation (as measured by exotherm or other in-process check) must take place before the full quantity of halide can be added.
*Sadly, Dr. Hulshof's passing was noted in OPRD recently.