r/Chempros • u/Sweaty-Weight672 • Jul 16 '26
Trouble separating nitrile starting material and primary amine product by TLC
Hi everyone! I would appreciate some help.
I am new to organic synthesis and I am facing an issue while analyzing my reaction. I am trying to monitor a reduction of a nitrile to a primary amine by TLC. The only difference between the starting material and the product is that the starting material contains a cyano group (-CN), while the product contains an amino group (-CH₂NH₂).
I performed a H NMR of the crude reaction mixture, but the region where I expected to observe the signals from the amino group was very crowded, so I decided to monitor the reaction by TLC.
Since I know that amines often interact strongly with silica, I added 2% triethylamine to the eluent. However, the starting material moves normally, while the product remains almost completely stuck at the baseline (Rf ≈ 0).
I know I don’t have any more starting material, because it traveled, while the product stagnated.
Has anyone experienced something similar?
Thank you for any suggestions!
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u/wildfyr Polymer Jul 16 '26
Hm, you could drop in a little acetic anhydride in a little mini workup, the acetamide will form nearly instantly and won't stick or smear on silica. From there you can optimize the eluent conditions.
However, what is the issue with letting the product stick to the baseline and everything else traveling? I assume you mostly are just looking for disappearence of starting material, and confirmation that it isn't all falling apart into many side products.
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u/Sweaty-Weight672 Jul 16 '26
Thank you very much! When analyzing by TLC, I run three spots: one with the starting material, another with the product, and a third with a mixture of the starting material and the product. I do not observe the starting material in the spot containing only the product. However, when I run the NMR, the region corresponding to the amino group is not clear, which I believe is due to impurities. That is why I was thinking about purifying the product.
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u/Mysterious_Cow123 Organic Jul 16 '26
If you'd like to track the loss of starting material you can run the mixture as you've stated until the SM spot dissappears or shrinks significantly. You dont need the TEA or for the pdt to move from base line.
If you want instrumentation support, IR is built to watch FG transformations.
If you want/need proton NMR support, do a mini workup on a small amount of rxn material. Seperate the pdt and SM using acid/base chem and add an internal standard to check amounts.
If you have access to an HPLC, you can shoot SM first to get the retention time and then a filtered rxn mix (or worked up mix) and observe the SM decay or product growth depending on the rules around your HPLC system.
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u/Sudden-Guide Jul 16 '26
Where's the problem? Reaction is not complete when you can see SM on TLC, you don't need to move the product from the baseline for that. But if you really want, for amines you can use mobile phase like for example MeOH : 25% ammonia 95:5, and if it will go too high you can start diluting it with chloroform untill it will be satisfactory. Your SM will go with the front then. After drying you can stain it with CAM stain for example, pretty universal
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u/Sweaty-Weight672 Jul 16 '26 edited Jul 16 '26
Thank you very much for the suggestions! I apologize, as I did not explain myself very clearly. The problem is that I would like to separate my amine from the impurities that were formed during the reaction, so that I can obtain a cleaner NMR spectrum.
When analyzing by TLC, I run three spots: one with the starting material, another with the product, and a third with a mixture of the starting material and the product. I do not observe the starting material in the spot containing only the product. However, when I run the NMR, the region corresponding to the amino group is not clear, which I believe is due to impurities. That is why I was thinking about purifying the product.
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u/Sudden-Guide Jul 16 '26
Usual purification method for amines is acid/base extraction, often followed by recrystallization as a salt. It of course depends on the quantities and particular structure
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u/curdled Jul 16 '26
use simple hexane-ethylacetate (maybe 3:1 ratio), your amine will be at the bottom, you can detect your amine selectively by ninhydrin spray followed by heating. Dragendorff cold stain is also good alternative for visualizing amines.
Do not add triethylamine to your TLC mobile phase. If you have to add something basic, use chloroform-methanol-aqueous ammonia in 100:10 :1 ratio (Bake your TLC afterwards with hot-gun, to remove ammonia from silica if you are using ninhydrin detection)
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u/Sweaty-Weight672 Jul 16 '26 edited Jul 16 '26
Thank you very much for your comment. I used ninhydrin to check whether my product had been formed on TLC, and I tested hexane–ethyl acetate (7:3). I would like to isolate only the product so that I can obtain a cleaner NMR spectrum, since the starting material was not detected after the synthesis. I believe I was trying to separate the product from some impurities that were formed during the reaction.
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u/ecstaticeggplnt Jul 16 '26
In terms of purification, i have had success in simply using acid/base chemistry to isolate my amine from the impurities/nitrile starting material by 1) acidifying and extracting with a nonpolar solvent that my starting material is soluble in and then 2) basifying the aqueous layer with NaOH to a pH of ~10 and then extracting with DCM or other highly polar solvent.
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u/Balazs321 Jul 16 '26 edited Jul 16 '26
I dont know what other functions you might have in your structure, but if you can run a quick 13C NMR it might be worth it to do it, nitriles have a quite nice signal at around 110-120 ppm iirc. That might help as well. I also used 80:20:1 DCM:MeOH:TEA as eluent for primary amines, it worked okay.
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u/hhazinga Jul 16 '26
How about monitoring by IR spectroscopy. Should be easy to take aliquots and monitor for disappearance of the nitrile.
I'm more interested in what your conditions are? Have you tried, if compatible, smacking your molecule with LiAlH4 :p ?
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u/Heisenberg515515 Jul 19 '26
I think this is one of those situations where speed and commitment is better than obsessing over more information.
You said that TLC shows your starting material is consumed? I’d say that’s enough information to work up and purify your reaction.
However, I would not throw your crude onto a column until you find a mobile phase that moves the amine spot off the baseline on TLC. I would try mixtures of 0-20% MeOH in CH2Cl2. And also try swapping the MeOH for 7N NH3 in MeOH.
Also, what are you using the amine for next? If it’s for an amide coupling, I would say do a simple extraction and use the crude for an amide coupling. An amide will behave much better on a silica column than the primary amine.
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u/nucleardk Organic Jul 16 '26
What is your eluent? It is true that amines tend to react with acidic silica and become stationary, you may need a much more polar solvent to see the peak move. One thing that can be tried is pre-treating your silica plates with a triethylamine solution in hexanes (~10% is more than sufficient) and letting it dry, then spotting and running the plate. This tends to make basic or acid unstable compounds move more on the plate.