09-27-04 11:20
No 533415
Hello. I have tryed to crystallise som tma-2 freebase solved in ether with pregassed toluene, the precipitate is very fine powered and hard to filtrate at small qantity.. I wonder if there is a good solution on this problem? would i get bigger crystall with pregassed DCM? The secound problem i observed was a yellow colour on the solution after the toluene*HCL vas added.. Dis completely destroyed the hole project
, i read in the search engine thet this could be water present in the freebase/ether.. could this also bee something else?? to low pH or something... because the ether was dried on a rotavapour and solved in ether dried with MgSO4. I tryed to do a A/B to recover my freebase and then solved it in MeOH and addjusted the pH to 6,5 and evaporated the alcohol.. but then i only got some greasy crystalls... Is there any experts on tma-2 crystallisation here??? 
I have tryed the shulgine route with IPA and ether to... that works but the water in the HCl makes some trouble and
the IPA also tyrned yellow...
(Newbee)
09-27-04 12:25
No 533425
I would rather use a mixture of nonpolar and water-miscible solvent - or better said: pregassed IPA/EtOH/MeOH rather than toluene...
Try dissolving your amine in EtOAc (or ether) and add pregassed IPA/HCl until pH 5, then add acetone, and chill in the fridge for several hours. Use a fine-pored fritted funnel (those small ones for analytical filtration are great), with a porosity of 3 or better 4 (0 is the most coarse, 5 the finest porosity).
This should allow you to filter the crystals even if they are very small. But filtering takes some time with such fine pores, even with vacuum.
Alternately, you could try forming the sulfate by adding 5N IPA/H2SO4 dropwise until pH approaches 6 and then adding dry acetone, cooling and filtering - amine sulfates are not as hygroscopic as amine hydrochlorides and therefore easier to make...
indole_amine
(Hive Bee)
09-27-04 14:32
No 533440
EtOAc, good sugestion! thanks.. miscible with alchohol and acetone as well, could add ether instead of acetone maybee?... Have you tryed pregassed DCM, i think its a litle polar and might solve some amine?? true?
(Hive Bee)
09-28-04 05:37
No 533549
I got nice crystalls from EtOAc with pregassed 100% EtOH and Acetone, filtered trough filter nr.3! Nice TMA-2 powder mp- 187,9-188,1 ! Thank`s..
09-28-04 09:10
(Rated as: misinforming)
(Chief Bee)
09-28-04 16:53
No 533662
The only problem is that ether requires thorough drying, as the solvent traces in the crystalline mass attract water from the air
That is incorrect and that theory has no factual basis.
Ether evaporates long before it has any chance to absorb water. Any ether-wet crystals will be just as hygroscopic (if not more) when the ether is gone. It would greatly surprise me if methanol would absorb water at a faster rate than it evaporates as well.
The Hive - Clandestine Chemists Without Borders
09-28-04 18:10
(Rated as: misinforming)
(Chief Bee)
09-29-04 01:53
No 533662
The only problem is that ether requires thorough drying, as the solvent traces in the crystalline mass attract water from the air
That is incorrect and that theory has no factual basis.
Ether evaporates long before it has any chance to absorb water. Any ether-wet crystals will be just as hygroscopic (if not more) when the ether is gone. It would greatly surprise me if methanol would absorb water at a faster rate than it evaporates as well.
The Hive - Clandestine Chemists Without Borders
(Hive Bee)
09-29-04 17:17
No 533755
Maybe I live in a very humid climate...
(the fact that ether washed hydrochlorides become wet before having dried is just empirical data. This is not the case with acetone)
And even if you have fairly dry methanol and evaporate it in a flat dish at room temp., it will take up water traces from the surrounding atmosphere before all of it has evaporated. And this is empirical data too...
So, the correct statement would be: I don't know why ether and methanol gave wet crystalline masses in all my pevious experiences with crystallizing hydrochlorides. From my point of view, acetone is the solvent to use for rinsing before drying is attempted. Because I didn't experience said wetting when rinsing with it, I recommend it.
Don't know why, but it works best.
And still:
The reason why acetone is added is to diminish the overall solubility of the amine salt. If no acetone is added, some of your product will dissolve in the small amt. of EtOH. By adding dry acetone, you create conditions similar to a dual-solvent reXtalization (amine*HCl dissolved in minimum boiling alcohol, acetone added and cooling applied to precipitate again).
indole_amine
(Chief Bee)
09-29-04 20:15
No 533770
Maybe I live in a very humid climate...
Do you experience this kind of hygroscopy in the winter as well?
(the fact that ether washed hydrochlorides become wet before having dried is just empirical data. This is not the case with acetone)
I believe it is much more likely that the acetone washes away whatever hygroscopic contaminants you may have present in the crude product, while the ether and methanol does not (this assuming that you are perfectly sure that all your solvents are dry).
An experiment to distinguish between these effects can be made by taking an amount of dry crystals previously washed with acetone and then divide it into two piles. One of the piles are wetted with anhydrous ether, which is allowed to evaporate. Afterwards the ether-treated crystals should be at least as dry as the un-treated pile placed next to it.
The Hive - Clandestine Chemists Without Borders
(Hive Bee)
09-29-04 22:33
No 533792
I dont think the big problem here is the humidity in the air... Ether is sligthly polar with the oxygen in the middle and got a possibillity to make hydrogen bonds to eks water in small amounts.. Acetone work vell, and the solubillity of the amine is low in it, so you dont need to rextallise as you would with MeOH.. Pregassed MeOH instead of EtOH would not make any difference as long as the alcohol is dry..
(Hive Bee)
09-30-04 00:58
No 533800
I believe it is much more likely that the acetone washes away whatever hygroscopic contaminants you may have present in the crude product, while the ether and methanol does not (this assuming that you are perfectly sure that all your solvents are dry).
Good point, this could be a good explanation!
About air humidity and winter: my "empirical data" is indeed from the hottest months of the year (ether seemed the most volatile solvent to me back then). We'll see - just the right season to experiment on that...
Grignard: well acetone is slightly polar, too - or not? But I too think acetone allows for more water being present without getting muddy crystals. So it could well be that it binds more H2O molecules (or does so with more ease) than ether does.
Besides, acetone is way cheaper, easier to handle (not nearly as dangerous) and you don't get that nasty buzz from it...
(think I will try wetting some crystals with ether and some with acetone (both completely anhydrous of course), and see what will be left after evaporating the solvents...)
While we're at it: has anyone experience with using chloroform for gassing? Some amine hydrochlorides are soluble in it, but it could be easily stripped with vacuum, and then, flooding with dry acetone should result in a nice in-situ recrystallization...
indole_amine
(Hive Bee)
09-30-04 11:56
No 533888
Why use chloroform when there are other good solvents? It is poisonous and carcinogenic. It can also form phosgene upon storage unless stabilized/kept in the dark (stabilize with ethanol if not supplied stabilized).
In addition, chlorinated hydrocarbons are bad for the environment (but can of course be recycled).