ABSTRACT
The prototypical Grignard reagent preparation involves the reaction of an alkyl or aryl halide (RX) with magnesium (Mg) in an ethereal solvent, under reflux conditions [ 1 ,2]. Initiation of this reaction should occur within the first 1 0-20 wt% addition of the RX solution. Evidence for this initiation is a large exotherm, and a visual change of the magnesium turnings from a bright-shiny silver color to a dull gray-black. Many chemists look for this color change in the magnesium or solution, but this can be misleading if the agitation is strong enough to shear the magnesium (see Chapter 4). Until initiation has been confirmed, no more than 20 wt% of the RX charge should be added to the reactor. Otherwise, one risks initiation of this exothermic reaction after all of the RX has been added. This is one of the major hazards in the Grignard reagent preparation, because the resulting rapid exotherm will cause a release of the reactor contents into the atmosphere. Therefore, an appropriate hazard review should be conducted before carrying out this reaction [3,4] . From a laboratory safety point of view the following precautions are recommended:
1 . Isolate reaction setup i n a hood. 2. Place a spill tray beneath the flask. 3. Install a vent relief and a surge flask to prevent the release of the RX-solvent
mixture to the environment. 4. Use tetrahydrofuran (THF) instead of diethyl ether (EtzO). 5. Use activity measurements (see Chapter 6) to determine if initiation has occurred.
