Sodium hydride (NaH) is typically stabilized and stored in mineral oil. In its pure form, it reacts violently with even trace amounts of water or alcohol, releasing hydrogen gas and heat, and is highly prone to fire and explosion. It is insoluble in organic solvents. As a strongly basic hydrogen anion reducing agent with a pKa of approximately 35, it is commonly used in organic synthesis for deprotonation, elimination reactions, and condensation reactions, as well as for the preparation of alcoholates, thiolates, and various carbocation intermediates.

Sodium Hydride as a Base and as a Reducing Agent

Sodium hydride is a commonly used base for deprotonation of alcohols, phenols, amides, ketones, esters, and other functional groups for the promotion of their nucleophilic substitution. Typically, sodium hydride and the reagents are mixed in polar aprotic solvents such as DMSO, DMF, or acetonitrile for these SN2-type reactions. Whereas the literature is replete with examples of the use of these solvents in such reactions, our chance discovery of reactivity of sodium hydride with two of these commonly used solvents, DMF and acetonitrile, indicates that certain undesired side reactions involving these two solvents might be common, but unrecognized. As is disclosed in this report, the root cause of these complicating side reactions is the dual role that sodium hydride exhibits as a base and as a source of hydride. The type of byproducts that will be disclosed in this report are generally difficult to detect with common visualization methods and are easy to overlook. Using benzyl bromide as the electrophile helped us to isolate the byproducts by UV detection and the structures were ultimately assigned by X-ray analysis of single crystals. Sodium hydride can behave both as a base and as a source of hydride. This dual ability in the presence of an electrophile such as benzyl bromide results in the formation of byproducts when dimethylformamide or acetonitrile are used as solvents for these reactions.[1]

Sodium Hydride in Aprotic Solvents

It's a reagent combination whose hazards have been noted before, but a lot of people don't seem to know about it: sodium hydride in DMSO or other polar aprotic solvents. And yeah, I've used that exact combination, too, many times. But I did those reactions (for the most part) before I was aware of the possible hazards, and they have mostly been on a rather small scale and mostly at room temperature. Scaling up any such preparation, especially with heating, is a very bad idea. Severe explosions have been reported for over fifty years, as the new paper linked above details, but people still use these conditions without knowing that. This paper notes that the major organic chemistry titles publish dozens of papers a year with these reagent combinations in the experimental sections. When you use sodium hydride /DMSO you're forming the dimsyl anion (deprotonated DMSO), and that is not a stable species (as was first reported in the mid-1960s). If you know how to read a differential scanning calorimetry (DSC) plot, the one at right may well interest you. And even if you don't, you can see those lively spikes in heat flow and appreciate what that's going to mean if you have a decent-sized reaction going. (The inversion around 20C is, naturally, the melting point of DMSO - it's always been a good indicator of a cold lab!) Whether or not you experience the second spike after the first will be a function of how large a reaction you have going, how well it's mixed, and how much heat you can transfer out of it (and how quickly). Local heating in such cases can send things into a runaway decomposition.[2]

For an illustration of that, see the photo at right. The left-hand panel is a Hastelloy accelerating-rate calorimetry (ARC) cell, before and after doing a DMSO/ sodium hydride run, and the right-hand panel shows the ARC apparatus itself after said assay. You don't want this. You especially don't want this when your reaction vessel is not contained within a large calorimeter, but is rather a Pyrex round-bottom in the middle of your fume hood. This was a loading of 4.5 grams of a mixture of 84% DMSO and 9.7% NaH (the rest was the mineral oil from the sodium hydride). In case you're wondering, that model ARC cell has an average burst limit of about 14,500 psi, which should inspire some serious thought. But you're not off the hook with DMF or DMA, either. The temperature where trouble hits is a little bit higher in those cases, but they're trouble just the same. An analysis of the gaseous byproducts from the DMF/NaH decomposition showed hydrogen, carbon monoxide, methane, and even ethylene/acetylene, which argues for a radical chain mechanism, at least in part. In all cases, the more sodium hydride in the reaction, the lower the temperature where decomposition sets in.

References

[1]Hesek, D., Lee, M., Noll, B. C., Fisher, J. F., & Mobashery, S. (2009). Complications from Dual Roles of Sodium Hydride as a Base and as a Reducing Agent. The Journal of Organic Chemistry, 74(6), 2567–2570. https://doi.org/10.1021/jo802706d

[2]Lowe, D. (2019, August 14). Sodium hydride in aprotic solvents: Look out. Science Blog – In the Pipeline. https://www.science.org/content/blog-post/sodium-hydride-aprotic-solvents-look-out