Here’s a safety warning for my fellow synthetic organic chemists. 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 NaH/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.
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/NaH 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.
So strongly consider alternative solvents or bases for such reactions, especially if you’re working on any kind of scale. And most definitely don’t heat them up! Most industrial process chemists are aware of these hazards (or should be!), but a lot of academic and industrial synthetic chemists aren’t, or don’t realize how bad the problem is. The fact that these combinations are used pretty often shows that you can get away with them under “ordinary” conditions, but the problem (as always) is that you never quite know when things are going to stop being ordinary – and then it’s far too late to do anything but hope you’re not nearby.