[tomek]

Hey,

I am trying to separate two isomers I get from the reaction of isocyanate and amine. They separate on TLC alright although difference in Rf is very small. When I want to transfer that method to column the problem is that those compounds are virtually insoluble in any solvent (apart from DMSO). So when I run the column they slowly disolve in eluent (hexane-EtOAc) and bands diffuse. They say if your compounds are insoluble in eluent you're using dryload but that doesn't change the fact I still need some solubility in eluent. Crystallization is also difficult, however I managed to have some succes using fractional crystallization with some of my compounds. I was wondering if someone had similar problem and managed to solve. Any suggestions would be greatly appreciated. Thanks.

[Arkcon]

If you have access to an HPLC, you can get better separation.  Even better, if you use a chiral column.

[discodermolide]

If they slowly dissolve in hexane-EtOAc then they must be soluble in EtOAc?
Is this the case? If so then they may crystallise apart?
Maybe isopropyl ether/EtOAc mixtures for the chromatography? Check it on TLC.

[Dan]

I have had several cases where the presence of hexane causes precipitation on the column. I have found that solubility problems in chromatography are often solved by running in eluents where toluene, chloroform or DCM are the weak solvent.

e.g. A compound that behaved as you described in 30% EtOAc/hexane eluted beautifully in 10% acetone/toluene.
e.g. I had another ridiculously crystalline product that eluted beautifully in 5% ethyl acetate/chloroform.

[tomek]

The problem is those compounds don't dissolve in toluene, chloroform, DCM, EtOAc (or dissolve sparingly - one time I weighed residue from EtOAc fraction eluted from the colum which was circa 70ml and found out I had about 10mg compound there, where I initialy had loaded few hundreds of miligrams). Have anyone tried running the column with pyridine, DMSO or something similiar. DMSO is the only solvent that dissolves most of my compounds but using it for the column seems like a bad idea. But anyway thanks for the suggestion, nevertheless I'll try them.

[discodermolide]

You can't really elute a column with pyridine or DMSO you will get a mess.
With this solubility it may be worth going for crystallisation.

[Babcock_Hall]

What about acetonitrile?

[Dan]

Is there another step? The isomers may be easier to separate after the next transformation.

[tomek]

There is no another step. These compounds are the final compounds although I'm thinking I might add one more ring to them. I get mixture of regioisomers (though at the same time it might be E/Z geometrical isomers of the first product that I'm getting) that's why I want pure samples to NMR them.

[OC pro]

By not knowing the rest R I think these compound should elute with CHCl3/MeOH + 1% aq. NH3 mixtures.
You should invest more time in making TLCs. There are plenty combinations. And if it moves on TLC you will also get them from the column if they do not DECOMPOSE on the column.

[Messi]

How about DCM?