[biomedical]

Dear Forum,

I have recently begun to work with L-lactide for polymer synthesis, and
all the available protocols suggest its purification by recristalization
prior to the reaction. The procedure involves heating ethyl acetate
and then dissolving the coumpound in small ammounts of solvent
while hot.
My problem is when i add just 1 or 2mL of solvent it quickly dissolves the reagent
and when i place it in ice to form crystals nothing appears...
In the literature its described that for 100mg it should be used 450mL of solvent,
but my reagent dissolves in just 1 or 2mL.
Could someone please aid me an indicate if i may be doing something wrong. Or if there
is another procedure better than the one i am currently using.

Thanks in advance for all the expertise on this matter.

regards,

Biomedical

[Babcock_Hall]

What was the mass with which you started?

[orgopete]

I cannot speak to the solubility of your compound, except to realize it must be more soluble than the examples you are following. None the less, when I did a resolution by recrystallization, I had to choose a solvent system in which less than half of my material was recovered. You should be able to find a solvent system in which you can achieve a similar result. You should be able to scout solubilities quite easily with small samples. If you use mixed solvents, this may be accomplished in a very short amount of time.

[Babcock_Hall]

I have to wonder about the solubility value you were given; it just does not sound correct.  If it were correct, I would consider looking for another solvent.  I sometimes check solubilities with one or more test tubes and weighed out samples and/or measured volumes of solvent.  The other good thing is that if something does not come back out, one can always remove the solvent by rotary evaporation.  I don't know your level of familiarity with organic purification techniques, so I hope that this comment does not come across as condescending.  It is obviously not intended to be.

[Dan]

I have to wonder about the solubility value you were given; it just does not sound correct.

I agree with this. 100 mg in 450 mL sounds unlikely.

This paper popped up following a quick google that suggests in the abstract that the solubility might be more like 50 g lactide in 100 g EtOAc.

For a small quantity I would suggest suspending the crude in a couple of mLs of refluxing hexane, then adding EtOAc dropwise until you have a solution, and finally let it cool. The presence of hexane should lower the solubility sufficiently so that you can purify small amounts with a volume that is practical to handle.

[orgopete]

Babcock_Hall has described a very good procedure to follow. I had often done something similar, but with less rigor, soluble v insoluble for starters. None the less, I would ignore all prior solubility advice, except if you have identical compounds with identical purities. An impurity can have a significant effect upon a recrystallization.

If you are using L-lactide to also purify your starting material, impurities can also have a profound effect upon the solubility. If that is true, the product may seem far more soluble than the pure compound. This should only reinforce the value of the procedure suggested by Babcock_Hall.

This is how I would do it. I'd scout solvent systems to find a system that I found workable. I would then adjust that system so I could get approximately a 50% recovery (assuming a perfect 100:0 ratio of solubility). I would strongly suggest using a two solvent system because it is most easily adjusted. This can work well except for very soluble or insoluble compounds. Then repeat, repeat, repeat.

[IsotopeBill]

I like Dan's method of suspending your solute in a solvent in which it is insoluble, then adding the other solvent to dissolve it.  I've had good success with this procedure when dealing with very soluble compounds.