[Ingeniosuccinimide]

Could anyone please give me the solubility data for phthalimide in DCM at room temperature (or near room temperature)? I have some issue with the sample we have in our lab and I need some official data as a reference.

Apart from DCM chloroform can also be used. I was unable to find any reliable data so far.

[discodermolide]

Why don't you buy a small quantity from Aldrich and do the experiments?

[Ingeniosuccinimide]

Why don't you buy a small quantity from Aldrich and do the experiments?

I have 1 kilo of that stuff in the lab. The point is that I need some official source which states the solubility, besides that phthalimide dissolves in DCM quite poorly, and it is something slightly unexpected.

I don't know any other non-polar solvent that dissolves phthalimide nicely. If anyone has some official data or at least a suggestion where I could check that would be nice. Tried With wikipedia and CRC handbook but that was not helpful.

[discodermolide]

There are three things you can do:
1 ask the manufacturer
2 do the experiments yourself
3 try a melting point.

Data such as this are not usually compiled.
It is actually a compound which is quite insoluble in a lot of things.

[Ingeniosuccinimide]

I tested at least the general solubility (on scale 5mg per 1 mL) in a series of solvents, and the only suitable solvent seems to be DMF. Other reaction components are also soluble in DMF.

The only question that remains is how to get rid of DMF when isolating the product (if the reaction will work)? I never perfromed any kind of reaction in pure DMF.

Is it a very unpleasant solvent to get rid of? The original procedure I'm following for a different series of substrates involves flashing with hexane:EtOAc or DCM:EtOAc after concentrating the reaction mixture in vacuo. How difficult is it to evaporate DMF on a common rotavap (due to the nature of the potential product nothing should be warmed above room temperature)?

Also, how should DMF behave on a flash column? Should it be easily retained on silica or maybe eluted very quickly?

[clarkstill]

Tricky, tricky... On a common Buchi at room temperature (without very good vacuum) you'll have serious difficulty removing DMF. It can also be a pain on the column, as it tends to pull the product (and all the impurities) through, if there's a reasonable amount of it. However, if your product is soluble in diethyl ether, you may have a solution: DMF doesn't mix with ether but does with water, so if you dissolve your crude residue in a large volume of ether and wash multiple times (at least 5) with aqueous 10% MgSO4 or 1M HCl, it tends to do the trick and wash away the DMF. Other aqueous washes might also do the trick, but these are the ones I've personally used.

[Ingeniosuccinimide]

I'm not optimistic when it comes to dissolving the product in ether, on contrary, for previous analogues the next step after flashing was to recrystalize the wanted product from DCM by adding ether, since two very simillar compounds (main product and byproduct) go out together on flash.

All what I managed to do is to further test the solubility, and I found that the mixture DCM:DMF up to 5:1 can be used to dissolve the reactants, after that phthalimide will precipitate if I add more DCM. Maybe I can run the reaction in that system and decrease the amount of DMF, but still the issue with removing remains when I want to rotavap the crude.

Is DMF really so nasty on silica columns? What about some other stationary phases like acid/basic/neutral alumina, florisil or sth similar?

[wildfyr]

DMF is not something you want on your column, it will likely cause your band to badly broaden, and might cause general streaking.

You could add water and DCM to the reaction then extract it multiple times with water, which is extremely standard for DMF reactions, but it does depend on your product being more soluble in DCM than water. Chloroform is also an option. You could try Ethyl acetate as a hail mary, but Ive never seen that done with DMF, would probably need to do more than the typical 3 water extractions.

If your stuff is heat tolerant/not volatile you could try doing a simple distillation, DMF boils at 153C at 1 atm. If you have a  high vac setup this is probably pretty trivial, can be done by directly hooking up the hi-vac pump to the rotovap, or just on a shlenk line. If not this could be a gamble against time for your compound breaking down if it is not thermally stable.

[MOTOBALL]

My reading of your situation is that you have two, unrelated, problems and I would suggest that you resolve each separately.

1.  Removal of DMF from the rxn mixture---I'm assuming, from phthalimide, that your desired product + major byproduct are both insoluble in water.  Therefore, quench the rxn with crushed ice-water, (DMF slowly into excess ice/water or vice versa).  Filter the ppt, wash well with several aliquots of water, dry.

2. Use tlc on silica gel plates to perform scouting expts; determine a mobile phase, that after 3-4 developments sequentially will give adequate resolution of product/byproduct.
Suppose EtOAc (100%) gives Rf ~0.9 with no resolution & Hexane (100%) gives Rf ~0.01.
Start with EtOAc/Hex 1:4 v/v, run the plate 3x, with thorough drying of the plate after each run.
Adjust EtOAc/Hex ratio to optimize the tlc separation,with Rf ~0.4-0.7 for the two products.
This will give you an idea of the likely behavior on a column.   Separate by dry-column chromatography.