[kriggy]

hey, im looking for any practical experience with this matter. Im trying to crystalize an acid and so far Im not able to get any crystals even on very high concentration (1M). I tried different solvents (alcohols, ACN, acetone, ethylaceate). I think my best bet now is to change the resolving agent (which im going to do when I get them).

Im looking for some practical tips or knowhow that realy cant be found in papers.. does the order of addition matter? or how do I analyze the sample to see if the salt is formed or not? Or why usualy polar solvents are used compared to solvents like toluene or whatever else

[crawlingmcedge]

Cannot give much help if you don't provide details on the sample and resolving agent.

Try slower crystallization in diffusion chambers. That did the trick for me a couple of times.

[TheUnassuming]

In my experience, there are some general good practices that are similar to all small molecule crystallography, but otherwise the best method I've seen is essentially a brute force slog to find the best crystallizing conditions. Its a very good idea to run a wide variety of resolving agents (amines in your case) in a variety of solvents/solvent combo's.  I think many major vendors actually sell plates for higher throughput screening of conditions (aldrich:https://www.sigmaaldrich.com/technical-documents/articles/chemfiles/facile-and-rapid-chiral0.html).  Its not cheap, but not as expensive as buying all the bases yourself and screening them one by one. 

To try to answer your questions:

Order of addition shouldn't matter because of the time frame you are working with. 

For quick and dirty results you can analyze the mother-liquor to see if you get an appreciable ee of the remaining acid.  More thorough (and necessary to fully qualify conditions) is to isolate the acid from both the mother-liquor and the crystal.  I prefer chiral HPLC, but a polarimeter will work after you isolate your acid from each sample.

From my own experience, the more greasy solvents were too non-polar to keep the salt in solution, making it all crash out and I wouldn't get resolution. 

Good luck!

[kriggy]

The kits looks good but its probably not the stuff I could buy. Took me some time to convince my boss to buy several resolving agent to try dutch resolution (using tree reagent at once, usually two are rather cheap but the third one is always shitty expensive)

btw what are reagent you have good experience with?
Also, if anyone if you used 1-phenetylamine, I read inthe literature that its its lot of times crystalized from water but its not very water liking molecule..but I suppose it only depends on the structure of the salt not of the resolving agent right?

[TheUnassuming]

Its been a while, but if I remember right the best results I got were with a nitro-phenethylamine in an alcohol/ether combo.  A pseudoephedrine isomer also gave some decent results too, but I can't remember the solvent set for that one.

Yes, its more important what the salt is soluble in rather than the individual non-charged species.

[kriggy]

How did you get the nitro derivative? AFAIK its not very available commercialy or its very expensive for the amounts required and the synthetic procedures I know about get the mxture of o-p isomers but dont describe their separation.

Im currently getting oil in MeOH+Water (suspending in water and adding alcohol till it disolves at reflux, but maybe adding water into the alcohol will give better results) but the alcohol-ether looks easy to try