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I sometimes face the challenge of explaining to my organic chemists that, even if no impurity signals are visible in their 1H spectrum, other signs (like FID shape, very poor s/n compared to what could be expected with the sample qty, broad peaks, bad resolution...) indicate that clearly, something is wrong with their sample. Everybody would agree that it's way much easier to convince an invidual based on concrete facts ("look, here we can see solvent/starting material/side product/isomer signals integrating for x% in your proton-nmr") rather than just doubts ("well, your structure is correct however something seems weird with the spectrum...Yet I can't see anything so I can't tell you exactly what"). Ultimately in these cases, I can't think of an easy way to get indisputable evidence of a purity issue, other than using quantitative NMR techniques maybe (which still won't tell me the nature of impurities). Purpose of my post is firstly for us to share personal experiences and discuss that topic. I'm also very interested if someone could provide me with a simple definition + common examples of paramagnetic impurities in order to explain to lab technicians the potential effects in small-molecule NMR measurements. Finally, I'm all ears if someone has good arguments, a straightforward method or eventually an idea of a good test sample that could be performed as an example to prove the point that having a nice LCMS chromatogram and no obvious imps in your 1H-NMR doesn't necessarily mean your compound is pure. Thanks in advance |
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Dissolved oxygen is the most common paramagnetic impurity that most people are likely to encounter. It is best to flush out the dissolved oxygen with nitrogen gas (preferably helium) - incomplete removal of oxygen can certainly degrade the quality of the spectra. Another source of degradation is the presence of particulate material consisting of suspended aggregates - dynamic motion of the sample between the aggregate phase and soluble phase can lead to considerable line broadening. This effect can be reduced by passing the sample through a filter. A sample containing such aggregates may look pure in LC-MS. However, during the preparation of the sample for NMR spectroscopy, concentration or solvent exchange or lyophilization may cause precipitation/aggregation. Some samples may aggregate over time, i.e., they have no aggregates immediately after passing through the filter, but the aggregates appear at a later stage. Dynamic light scattering can be used to measure the number and size of particles(aggregates) in solution. |
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Sometimes its hard to get a 'text book' spectra from even simple, pure compounds, I know, I've been asked to do it and spent some time getting the sample concentration/water content acceptable. I've very commonly found that to high a sample concentration for a given sample is the problem. For some inorganic (probably slightly paramagnetic) samples this can be more than a mg or so. For some simple organics, 50mgs or so. Occasionally I've made up a trivial organic compound in CDCl3, not too high concentration, sample peaks about twice that of the solvent; only to find the lineshape isn't good, multiplets can't be resolved. Diluting the sample by 10x usually works. (I suspect hydrogen bonding to be the blame) Residual water in the solvent/sample can sometimes confuse people too, if there's a lot and there's exchangeable protons in the sample the spectrum can be affected. That's without the chemistry this can trigger in some samples. Very dry solvent can show coupling to any -OH in the sample too, which again can confuse... (Eg dilute methanol in very dry cdcl3) Duncan |
