If you’ve ever prepared an NMR sample, you’re familiar with the fact that we almost always use deuterated solvents to dissolve our samples of interest. These special solvents, in which the majority (>99%) of hydrogen atoms have been replaced by deuterium, include lab staples such as: water (D2O), chloroform (CDCl3), dichloromethane (CD2Cl2), dimethyl sulfoxide (DMSO-d6), acetonitrile (CD3CN), methanol (CD3OD), acetone (acetone-d6), benzene (C6D6), toluene (toluene-d8), tetrahydrofuran (THF-d8), and trifluoroacetic acid (TFA-d). By using deuterated solvents, we can retain their respective solubilizing properties, while also ensuring that the solvent signal does not overwhelm the 1H spectrum we are acquiring. Conveniently, since no solvent is ever truly 100% deuterated, the residual solvent peak from each solvent (i.e., the small amount of regular proteo solvent that remains non-deuterated) is often used as an internal chemical shift reference. Finally, deuterated solvents are also commonly used as a field lock in NMR instruments! Now that we’ve confirmed their usefulness, it’s time to ask: how are deuterated solvents made!?
Historically, the most widely used approach for making one of the most popular deuterated solvents, D2O, involved the use of the Girdler sulfide process,1 sometimes referred to as the Geib-Spevack process. This approach takes advantage of the following equilibrium: