Troubleshooting: Spectroscopy

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Common impurities (with images)

Problem: Product peaks overlap, so you can't see coupling patterns, get accurate integrations or isolate individual protons for proton-proton correlation experiments.

Solution: Try a different NMR solvent- sometimes the peak of interest will emerge from the pack.   Often spectra taken in benzene-d6 have a different pattern than spectra taken in deuterochloroform.

Problem: My compound is not soluble in deuterochloroform.  

Solution: Try a new solvent. Depending on the compound, benzene-d6, acetone-d6, or deuteromethanol can solve this problem. Dimethyl sulfoxide is another option, but you will not be able to easily recover your sample from this solvent.    

Problem: Your spectrum looks different than it did the first time you made the compound, but you're pretty sure you didn't make any mistakes.

Solution: If there are only slight differences between the spectra, it may be that the two samples had different substrate concentrations. Sometimes the peaks of a more concentrated sample reflect bimolecular interactions.

Problem: I have a peak that might represent an OH or NH proton. How can I confirm this assignment?

Solution: Add a drop of D2O to your sample and shake vigorously for several minutes. The proton should exchange and the peak should disappear from the spectrum. You can also measure the spectrum in methanol-d4.

Problem: Ethyl acetate keeps appearing in my spectrum, even after the sample has been under high vacuum for hours.

Solution: Some compounds hang on very tightly to ethyl acetate. It can often be displaced by dichloromethane- if you add some to your sample and rotovap, and repeat once or twice, you will successfully remove the ethyl acetate.

Problem: You can't get accurate integrations for the aromatic region because of the deuterochloroform peak.

Solution: Try measuring the spectrum in acetone.

Problem: Your reaction seems very clean by TLC or GC, but after purification the1H NMR is COMPLICATED. Too complicated to be a simple mixture of diastereomers.

Solution: You might be looking at rotamers: try measuring the spectrum at a higher temperature, to increase bond rotation on the NMR time scale.

Problem: Even though I was very careful with my sample, my spectrum has large water peaks.

Solution: NMR solvents can collect significant amounts of water. One way to avoid this problem is to add an inert drying agent (like potassium carbonate or sodium sulfate) to your bottle of deuterochloroform.

Problem: I have an acetone peak in my spectrum.

Solution: It may be that your NMR tube had residual acetone in it. Surprisingly, after an NMR tube is cleaned, it takes 2-3 hours for residual acetone to disappear from a tube, even when the tube is dried in the oven.

Problem: My spectrum has very broad peaks.

Solution: A number of factors can cause peak broadening: poor shimming, a sample that is not homogenous (can be caused by poor solubility of your compound), or a sample that is too concentrated. If none of these seem reasonable, check with you NMR technician. The machine may need adjustments.

Problem: Your crude NMR looks awful. None of the peaks you expect are visible, and a lot of peaks you don't expect are cluttering the spectrum.

Explanations and Solutions: Crude NMR is not always the best way to determine whether your reaction worked. Situations when crude NMR is misleading:

  Reagent peaks dwarf product peaks. Sometimes a reaction has worked perfectly, only you can't tell until you remove leftover reagent.

  Solvent peaks dwarf product peaks. This is particularly true of reactions run in high boiling solvents, which are not always completely removed during workup.

  The reaction gave a mixture of isomeric products. In these cases, NMR of the crude mixture is extremely complex, but simplifies upon purification.

If you can identify a major product by TLC or GC, go ahead and purify your reaction mixture. You might be pleasantly surprised.

*If your problem is not on this list, post it on Q & A!*