Home >
Community >
How can I free-base my amine from TFA salt?
Upvote
VOTE
Downvote
+ Organic
Posted by
Mrs.Brie Zee.2U
How can I free-base my amine from TFA salt?
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).
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).
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.
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.
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).
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).
More
VOTE
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.
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.
More
VOTE
I already sent a sample for mass, now waiting for the result.
Does anyone have any other suggestion?
Thanks for all your reply.
I already sent a sample for mass, now waiting for the result.
Does anyone have any other suggestion?
Thanks for all your reply.
More
VOTE
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.
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.
More
VOTE
More
VOTE