[reflux]

I was curious what solvent systems have been effective for those who have purified very polar amines via column chromatography?  I have a compound that will only come off in MeOH/DCM with NH4OH or MeOH/Ethyl Acetate with TEA.  In either system it will streak and co-elute with several impurities.  Also I've noticed that basic alumina seems to be better for elution of the polar amine however separation is not as good as silica.  Even reverse phase HPLC does not clean this compound up so I am hoping for a better solvent system which will give me better resolution.  Any ideas?

Thanks!

[russellm72]

Hi,

You could try

(a) Amino silica

(b) Ion exchange chromatography.

Regards

Russell.

[reflux]

Found a good discussion of this on the Totally Synthetic blog:

http://totallysynthetic.com/blog/?p=979

Thanks I will look into those methods.

[zq]

I have used upto 30% methanol in ethyl acetate to purify polar amines by silica gel column chromatography.

[reflux]

Once again I am working with some very polar amines and amino alcohols... so I decided to resurrect this thread.  I will note that careful elution with a gradient of 1-10% MeOH/DCM with 1% NH4OH has worked the best for me when working with polar (nonaromatic) amines... so far.

Two new questions:
1) My key reaction gives me a mixture of isomers.  I think that two are secondary amines and one is a tertiary amine - does anyone know which is generally more polar, a tertiary or a secondary amine?

2) I have absolutely no experience with using DOWEX ion exchange resin.  I've noticed in a lot of preps that polar compounds are stirred with it before standard (silica gel or alumina) chromatography or just chromatographed on it.  What exactly does it do to aid in purification (i.e. why wouldn't I just put my compound on the standard column to begin with)?

Thanks for your *delete me*

[amancalledhorace]

A former collague (real 'old school') once recommended trying chloroform saturated with ammonia gas to me

I tried it and must say I was really very pleased with the results - though its a bit of a faff to set up

I bubbled some ammonia through a winchester of chloroform for a while and also deactivated the silica by bubbling ammonia through a slurry before loading the column. The ammoniacal eluent can be used in conjunction with other non-ammoniacal co-eluents (MeOH, Hexane etc)

/ H

[Captain Sci]

Sometimes, column chromatography of extremely polar molecules is not straightforward even with solvent mixtures that contain MeOH - and let's not forget that methanol can partially dissolve regular silica gel. In these cases, you may wish to consider alternative sorbents for chromatography that are less polar than normal silica gel.

Examples include the following:

1) cyano-functionalised silica gel (you can use this as a normal phase or as a reverse phase, depending on the solvent mixture that you employ; it is excellent for the chromatography of polar molecules)
2) Florisil (this is a magnesia-silica gel that is particularly useful in the separation of lipids, steroids, vitamins, complex alkaloids and generally for polar molecules)

I hope this helps

Athan

[da692]

heard wind of celite/silica mixture (various ratios, homogenize; industrial route) used for chromatography, never tried it though.

are you working w/ quaternary ammonium salts? you mentioned dowex IC resin and it got me wondering if you are dealing w/ the salts or free amines. if working w/ salts, chromatography can be painful. the ones i've dealt w/ tend not to like ether (ppt). good luck

[suku]

could you please let me know what is amino silica?

[Captain Sci]

Hello Suku and welcome to the chemical forums.

Amino silica gel is the product formed when "regular" silica gel is funcionalised with a molecule bearing the "NH2" functional group. For details of the functionalisation process and to see the structure of amino silica gel, please have a look at our web page by clicking on http://www.materialharvest.com/welcome/silica_products/functional_and_reverse.html.

Amino silica gel is retentive towards basic molecules and exists in "endcapped" as well as "non-endcapped" varieties. It is used in the separation of peptides, drugs and metabolites from physiological fluids; purification of sugars; separation of steroids, cholesterol and triglycerides; and as a weak anion exchanger for the purification of strong acids. It can also scavenge electrophiles and metals (including Zn, Pb, Cu, Co, Rh3+, Ru, Cd, Hg and Cr3+). In organic synthesis, you can use amino silica gel as a solid-supported reagent/catalyst to carry out Knoevenagel and Claisen reactions.

If you want more specific advice fee free to send me a private message or email. I would be delighted to help out.

Best wishes

Athan

[suku]

Hi Athan,
Thanks a lot for the information.
I am actually trying to purify opioids which are highly polar.
When i am trying to elute, the compound never elutes out, tried to elute with only methanol, it never comes. tried to add NH4OH but of no use.
can you please help me with this.

[Captain Sci]

Hello Suku

I can think of a few solutions to your problem - there are a number of purification sorbents that are worth tyring here, some in fact being much more affordable than amino silica gel.

I will contact you by email to discuss your problem in more detail. Feel free to also email me on athan[at]materialharvest.com.

Best regads

Athan

[russellm72]

Sorry this is an old thread but have you also considered using ion exchange chromatography?

You could see how u get on catching your amine on a SCX cartridge then eluting off with increasing concentrations of ammonia in methanol or something similar....

R

[AC Prabakar]

If it is free amine you can try to isolate/purify the compound by preparing it's salt(for example try Hcl or Oxalic acid).
There will be a difference in the tendency to form salt for 1° and 2° amine.Hence you can expect one compound as pure.
It may be easy to handle insted of column, especially in if the other impurities also polar!

[itsstar]

Dear Athan,

I have a mixture of polar compounds but i couldn't sort out the best solvent system for separating them. I'm a novice in molecule separations. When i used 50% Meoh in water the compounds moved completely with the solvent front on a TLC plate. Hoping for a valuable suggestion. Thanks in advance.

-Shan.