Sciencemadness Discussion Board

Seperation of amines(Post-alkylation) : Hypothetical

smaerd - 3-9-2011 at 07:45

(this is just a thought experiment might be kind of vague) Obviously this is going to vary from compound to compound. I'm only wondering about general traits and techniques involved in this sort of thing.

Say someone does an elementary alkylation reaction on an organic amine. The reaction goes to completion, and one is left with different proportions of the secondary amine, tertiary amine, and the lovely quaternary ammonium salts. How does one go about isolating these from one another in general.

To remove quat amines I have been reading but struggling to find solid information on adsorbing them on silica and activated carbon? Are either of these two practical?
Quote:
Tanada et al. (1991) studied the adsorption removal of benzalkonium chloride by granular activated carbon for medical waste water treatment; they found significant correlation between the amount of benzalkonium chloride adsorbed in less than 1000 ppm of equilibrium concentration and the micropore volume of activated carbon.


This thread on another forum describes using a silica plug? http://chemknowhow.com/forum/viewtopic.php?t=769

Are they saying that "most"(hate using that word) quaternary ammonium salts tend to bind not irreversibly but have a very strong affinity for the solid phase in column chromatography? This makes sense because of I.M. forces. Just trying to make sure I'm following correctly.

Here's a pretty cool paper about adsorption :)
Attachment: Adsorption at Silica, Alumina, and Related Surfaces.pdf (1.4MB)
This file has been downloaded 1661 times


After the separation/adsorption one is left with a secondary amine, and the tertiary amine(unless they isolated everything via chromatography). So isolating the two of these depending on the situation seems pretty tricky. The only crafty thing I could think of would be to treat them with an acid anhydride so that the secondary amine goes tertiary but the solubility would be very different from the other(assuming sterics prohibits the quat formation on the tertiary).

Is it more practical to employ means such as column chromatography, and short-path distillation(assuming decomposition happens before boiling) to separate these three? Or is this a case where an ion exchange column could be used?

Sorry this thread is practically reference-less but it's more of a question on technique than data, making it harder to find information.

If anyone knows of any good books(or e-books) about chemical separation's I would be very appreciative! It seems like a lot of books will tell you reactions, mechanisms, apparatus, reagents, etc, but good separation techniques seem kind of hard to come by. Thanks as always sci mad.

{last edit I promise}

[Edited on 3-9-2011 by smaerd]

Nicodem - 3-9-2011 at 09:24

Absorption:
Ammonium salts, just like all highly polar compounds and metals, can often be removed by filtration trough a plug of silicagel provided you use a proper solvent. Obviously you first need to check on TLC for the proper solvent which will push the other amines but keep the ammonium salt at the starting line. You then extract the ammonium salt from the silicagel using ethanol or methanol.

Chromatography:
Tertiary aliphatic amines can often be chromatographed on silicagel, while chromatography of the secondary and primary ones is often troublesome due to extensive tailing, but if you manage to find a proper eluent (usually made basic with ammonia or triethylamine to reduce tailing) you can hopefully separate all four by using a column (if you are lucky). This is not always a viable solution - chromatoghraphy of aliphatic amines is no trivial task. It is furthermore limited to lab scale synthesis. Anilines, heteroaromatic amines, azines and azoles usually represent no such problems in their chromatographic separation (for example, primary anilines do not tail at all on silica).

Extraction:
Extraction is generally only useful when one product is to be separated and the others discarded or further processed by other means. For example, some quat. ammonium salts can be very efficiently partitioned into water, but this is only limited to the hydrophilic enough. Some amines can be efficiently extracted into CH2Cl2, CHCl3 or even other solvents as hydrochlorides (from a diluted HCl solution). The amines are then regenerated by washing with a base. It is somewhat likely that only one of the amine hydrochlorides will be preferentially partitioned in the organic phase (if any at all) as this is not a common property.

Trituration:
Some quat. ammonium salts are insoluble in solvents such as acetone, hexane, etc., contrary to their prim-sec-tert amine counterparts, so that they can be separated by trituration, but you first need to have this information at hand. Trituration of salt derivatives is also very efficient to remove non-amine side products. Also trituration of salt derivatives of the amine mixture in alcohols or other suitable solvents can be used to remove minor amine side products from the major amine product, though recrystallization is a similar option to the same end. Still, I remember a case where I totally removed the secondary amine from the primary amine by trituration of their hydrochloride mixture in acetone (only the hydrochloride of the primary amine was insoluble). In such rare case recrystallization would not be an option because of the insolubility even at boiling and it would also not give an equally good recovery.

Distillation:
The best separation technique for the volatile amines is fractional vacuum distillation using a distillation column. Short path distillation or distillation without a column will not separate prim-sec-tert amines unless there is at least 100 K difference in their boiling points, but it will at least separate them from the quaternary ammonium salt, unless heated above the decomposition temperature.

Crystallization of salt derivatives:
An amine salt will efficiently precipitate if insoluble enough and often it is possible to find an acid to be useful in fractional crystallization. Crystallization of a salt derivative is obviously the best choice when only the major amine product is to be isolated and others discarded. It can be further purified by recrystallization. Though, the choice of the optimal salt derivative takes a lot of effort. The amine is then recycled by basification.

Selective decomposition:
If only the tertiary amine is to be isolated, other amines can be decomposed by acylation to make them neutral and the unaffected tertiary amine isolated by the virtue of its basic properties.






smaerd - 3-9-2011 at 10:15

Thank you so much that went over essentially everything I was curious about and really put me onto the right path. :D