A recent report is bringing chemists’ attention to a longstanding but frequently forgotten hazard in chemistry. Sodium hydride (NaH), when used with certain solvents, can unexpectedly generate heat and gas, leading to a runaway reaction or even an explosion (Org. Process Res. Dev. 2019, DOI: 10.1021/acs.oprd.9b00276).
Synthetic chemists often use NaH to pluck protons from molecules. But to get this ionic base into solution with greasy organic molecules, chemists usually have to use a so-called polar aprotic solvent, such as dimethylsulfoxide (DMSO), dimethylformamide (DMF), or dimethylacetamide (DMAc).
Reports that NaH in these solvents can lead to explosions date back more than 50 years, says Qiang Yang, a chemist with Corteva Agriscience who led the team behind the report. Nevertheless, he says, every year chemists publish papers that describe the use of these unsafe combinations. Yang’s team reports that between 2014 and 2018, Organic Letters published 38–62 papers/year with these combinations, the Journal of Organic Chemistry published 28−46 papers/year, and the Journal of Medicinal Chemistry published 67−94 papers/year.
“The most striking feature of this paper is the authors’ data compilation showing the abundance of recent papers that continue to use these hazardous reagent combinations,” says Suzanne Blum, a chemist at the University of California, Irvine.
Yang and coworkers also investigated the chemistry that makes these combinations unsafe. Yang says that radical reactions between the base and the solvents can generate gases, including dimethylsulfide and ethylene in the case of NaH added to DMSO.
“People should be aware of this safety hazard,” Yang says. “I haven’t used these combinations in my entire industrial career.” He points out that there are alternatives that can perform the same chemistry, although there is no combination that can be universally applied as a substitute. Tetrahydrofuran could be used as a solvent with NaH, and there are alternative bases, like alkoxides and hydroxides. “But scientists have to understand the stability of these bases with the solvents as well,” Yang says.
“The future work for us as a community is to integrate centralized hazards training into our graduate programs and to otherwise make finding hazards easier,” Blum adds. For example, she says, papers that use these conditions could be amended with hazard information that appears when readers click the articles online.