Issue Date: April 13, 2009
Chemical Safety Explosion Hazard
THE MERCK FROSST Center for Therapeutic Research would like to alert the scientific community of a potential explosion hazard associated with the reagent magnesium nitride (Mg3N2). We have been using this compound for direct primary amide formation from esters according to a recently reported protocol (Org. Lett. 2008, 10, 3623). This procedure, typically carried out in a glass microwave reactor vial, involves adding magnesium nitride to a solution of ester substrate in methanol at 0 ºC followed by sealing of the vessel. The mixture is then stirred at room temperature for one hour and heated at 80 ºC for several hours.
On at least two other occasions in our labs, reactions conducted in this manner have proceeded without incident. However, in a recent scaled-up application using 800 mg of an ester substrate, 1.3 g of Mg3N2 and 6 mL of methanol in a 20-mL thick-walled Pyrex tube sealed with a heavy Teflon screw cap and rubber O-ring, a violent explosion occurred approximately one minute after removal of the reaction vessel from the ice bath. This event occurred with a force sufficient to sever the metal holding clamp and completely shatter the thick-walled tube. Fortunately, no one was injured.
The published procedure calls for stirring in a room-temperature water bath for one hour prior to heating at 80 ºC. Immediately after the incident above, we contacted the authors of the original research paper. They informed us that the purpose of the water bath is to control a significant exotherm that accompanies the formation of ammonia from magnesium nitride during this stage of the reaction.
Because we were unaware of this at the time of our experiment, we had employed the commonly used practice of warming the reaction mixture to ambient temperature by simply removing the cooling bath. Under these circumstances, the putative exotherm would not have been sufficiently controlled.
Given the newly uncovered potential hazard associated with the use of this reagent, the published procedure should be followed exactly as written and only on a scale comparable with those reported in the original research paper. In addition, extreme care and precaution should be exercised by those who choose to use this protocol in the future.
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