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Author Topic: Residual peak in NMR after a column  (Read 739 times)

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clemi2310

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Residual peak in NMR after a column
« on: November 29, 2016, 06:07:40 AM »

Hello everyone,

Since several months I'm having troubles with some impurities in my NMRs. My final compounds have to be pure (>95%) for biological analysis.
Here an example of my reaction (see attached file)

I mix the reagents in EtOH with K2CO3, I put in under microwave irradiation and after 2 hours it's down.
Work-up:
- removal of solvent
- addition of Et2O + H2O
- Et2O extraction
- Drying and evaporation

Column chromatography: with EtOAc/Cyclohexane from 0 to 50% EtOAc with 40CV (around 30min)

After that, I get pure fraction in CCM, LCMS. I dry the oil under vaccun and then I do my nmr.
Product is okay, but few residual peaks are here around 1ppm and I don't know what it is.

1.42 ppm (probably some cyclohexane left)
but at 1.24ppm, 1.25ppm, 1.28 ppm and 1.33, no idea. It is not UV active since I do not see anything in the CCM or LCMS. But it's annoying me. I thought about grease but I don't use grease...

And these residuals peaks are here on every similar compounds with the same step. However, if I do a different reaction they are not present (it means it is not my deuterated solvent). I also tried new NMR tubes.

NMR is performed in CDCl3

Thank you for your help
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Irlanur

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Re: Residual peak in NMR after a column
« Reply #1 on: November 30, 2016, 04:19:48 AM »

are you sure that all reagents are clean? definitely no reaction by-products?
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clemi2310

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Re: Residual peak in NMR after a column
« Reply #2 on: December 01, 2016, 03:09:42 AM »

Well, NMR of starting materials are clean, and besides I see only one TLC spot, and one peak in LCMS with the corresponding mass...
I'm thinking of aliphatic impurities..
I tried a washing step with Acetonitrile and n-Hexane to remove aliphatic impurities in n-hexane.. It is drying under vaccuum I will see the NMR
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Irlanur

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Re: Residual peak in NMR after a column
« Reply #3 on: December 01, 2016, 04:49:55 AM »

Quote
LCMS with the corresponding mass...

Well are there other masses?

Of course it is also always possible that you have some form of chemical exchange. You could have an equilibrium between different conformations, which is not even that unlikely given the cycle. You could test this by recording an EXSY. Or for a cheaper variant try rising/lowering the temperature and observe the peak lineforms.
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discodermolide

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Re: Residual peak in NMR after a column
« Reply #4 on: December 01, 2016, 06:15:53 AM »

Looks like crap from the solvent together with some ethyl acetate.
Try distilling the solvents before use.
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Babcock_Hall

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Re: Residual peak in NMR after a column
« Reply #5 on: December 01, 2016, 12:03:43 PM »

"NMR Chemical Shifts of Trace Impurities: Common Laboratory Solvents, Organics, and Gases in Deuterated Solvents Relevant to the Organometallic Chemist" by Fulmer et al. (supporting information) Organometallics, 2010, 29 (9), pp 2176–2179
DOI: 10.1021/om100106e

This reference might possibly be helpful in identifying your impurity.  Someone posted it here years ago, and I am grateful for that.
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clemi2310

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Re: Residual peak in NMR after a column
« Reply #6 on: December 02, 2016, 05:01:52 AM »

Thank you for the reference but I already checked it, I do it with all my NMRs  since several years :)

The washing step with n-hexane/MeCN seems to work, I still have to dry more my sample, I will see. I have extra peaks around 1ppm But initial peaks are gone.

Probably aliphatic peaks from solvents ? Grease, I do not know. Hope it will work
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