Potential Safety Hazards Associated with Using Acetonitrile and a Strong Aqueous Base

Acetonitrile, a common solvent in organic synthesis, can be hydrolyzed in the presence of a strong aqueous base, such as NaOH or KOH, which can propagate into a runaway reaction. For a process recently reviewed in our laboratory, a possible loss of cooling incident during the desired reaction was found to have the potential to self-heat to the onset temperature of this hydrolysis reaction. This base-catalyzed acetonitrile hydrolysis was determined to potentially escalate into a runaway reaction, where it could lead to secondary exothermic runaway reactions of the reaction mixture. The use of acetonitrile was preferred for the initial cyclization step. Thus, adequate removal of acetonitrile prior to the following step avoided the process safety hazard posed by the hydrolysis of the acetonitrile solvent. The findings presented in this work serve as an alert to chemists and engineers for the potential safety hazards when scaling up a process in which the solvent becomes a reactant.