[hans50316]

Hello everyone

I first used trifluoroacetic anhydride to react with my amine to form a protecting group, it should be something like the picture below. However, the 1H-NMR spectrum showed there was a peak at 11.5 ppm which didn't match the NMR spectrum described in paper. Therefore, I believe there's a CF₃COO^- group attached on amine group .

I have tried to extract my product from DCM/water several times, then evaporated the organic layer, and according to the reference it should work. unfortunately it didn't. Also I've seen that amberlyst-21 resin might help but we don't have it.

So, any suggestion how can I freebase my amine?

[kriggy]

I think your 11,5 ppm peak is COOH from trifluoracetic acid left in reaction.

[salteen]

How far off is your 11.5ppm peak from the NH signal reported in the paper?  Protons on acids/amides have quite variable chemical shifts depending on the degree of H-bonding.  The signal can move quite a bit depending on how concentrated the sample is.

11.5 ppm could be from excess TFA in your compound as kriggy mentioned.  It's also a reasonable signal for the NH proton - I expect it is quite deshielded in this structure.  If you're concerned that you have acylated the twice, mass spec would be a quick way to check.

[OrgXemProf]

To purify and isolate your product you might consider a sequence of liquid-liquid extractions that take advantage of polarity differences among reactants and products. For example:

1. Make certain that you have hydrolyzed any unreacted trifluoroacetic anhydride that might be present in the product to trifluoroacetic acid.

2. Dissolve your reaction product in ether; then, place the ethereal solution in a separatory funnel and shake with 5% aqueous NaOH (or NaHCO3). If trifluoroacetic acid is present it will be extracted into the aqueous layer as the corresponding, water-soluble sodium salt. The ether layer now contains only basic and neutral components.

3. Separate the layers, discard the aqueous layer, and extract the ether layer with 5% aqueous HCl. Any unreacted amine will be extracted into the aqueous layer as the corresponding. water-soluble ammonium chloride salt, leaving only neutral compound(s) in the ether layer.

4. Separate the layers and discard the aqueous layer. Dry the ether layer over, e. g., anhydrous MgSO4, filter and evaporate. Hopefully, the residue will contain your desired amide. If any neutral (non-acidic, non-basic) impurities are present you should be able to further purify by fractional crystallization (lit. mp 86.0-86.5 degrees C).

An alternate procedure for preparing N-trifluoroacetanilide can be found here: Organic Syntheses, Coll. Vol. 6, p.1004 (1988); Vol. 56, p.122 (1977).

[hans50316]

To salteen:

The peak should be at around 7.5~7.8ppm according to paper.

Besides, the yield was 100% in a patent, and 95% in paper, and from my TLC plate test, there was only one spot on TLC plate.

[hans50316]

I tried extraction again by DCM and aqueous NaHCO₃, but it didn't work.

I already sent a sample for mass, now waiting for the result.

Does anyone have any other suggestion?

Thanks for all your reply.