NMR Solvent Selection

December 07, 2018 | Evaporator

When selecting a solvent for running Nuclear Magnetic Resonance Spectroscopy (NMR) analysis, typically a deuterated solvent is used in order to minimize background signals and provide a lock signal to compensate for drifts in the magnetic field¹.

However, there are several other factors to consider for NMR solvent selection:

• • Solubility
  • Interfering peaks
  • Price
  • Isotopic purity
  • Ease of NMR sample recovery

CDCl₃
With these factors in mind, a common “go-to” solvent for analysis is the deuterated form of chloroform, since it is relatively inexpensive with high isotopic purity, dissolves many compounds, and is easy to evaporate after analysis for NMR sample recovery (boiling point 61.2°C)³.

However, there are cases when CDCl₃ is not appropriate. In fact, there are many other solvents commonly used for NMR analysis⁴. Since no solvent is 100% deuterated, there will always be an observed ¹H peak for the solvent, which may interfere with the compound of interest⁵. Additionally, solubility might be a problem leading one to empirically determine an appropriate solvent. “For ¹H NMR, it is recommended to dissolve between 2 and 10 mg in between 0.6 and 1 mL of solvent so that the sample depth is at least 4.5 cm in the tube.”⁴ Thus, appropriate solubility must be considered in NMR solvent selection.

Let’s DMF/DMSO!  Compounds like DMF-d7 or DMSO-d6 have benefits to use as an NMR solvent as they are relatively inexpensive and can solubilize many compounds that are otherwise difficult to solubilize. However, in the past, it was difficult to remove these solvents due to high boiling points (153°C and 189°C), and thus running NMR with DMF or DMSO as a solvent was seen as a “dead end” for samples. This is frustrating and disheartening when forced to discard the most precious samples. However, a new instrument called Smart Evaporator has made it possible to evaporate solvents for quick NMR sample recovery, even directly in small 2 mL vials.

The Smart Evaporator uses a novel “Spiral Plug” technology to evaporate samples without any risk of bumping. It is particularly useful for high boiling point solvents like DMSO or DMF, but can also be used to dry down most organic solvents directly in a sample vial.

Here’s what our users had to say:
“The Smart Evaporator is perfect for small samples. I have found it especially useful for recovering material from DMSO-d6 NMR samples.”
– Dr. Tioga Martin, Asc. Scientist, Agensys, Inc.

“The Smart Evaporator is suitable for evaporation of samples previously measured by NMR.”
– Smart Evaporator User

For more information about the Smart Evaporator technology for NMR sample recovery and other dry-down applications, visit our page: https://biochromato.com/smart-evaporator/

For more testimonials, you can visit our page here.

References:

1. http://nmr.chem.wsu.edu/tutorials/basics/lock/
2. https://webspectra.chem.ucla.edu/NotesOnSolvents.html
3. https://web.nmsu.edu/~kburke/Instrumentation/NMR_Solv.html
4. https://www.chem.wisc.edu/areas/reich/nmr/nmr-solvents.htm
5. http://chem.ch.huji.ac.il/nmr/preparation/preparation.html