I did an coupling reaction between a diamine compound and the propynoic acid with PyBOP and DIPEA in DCM. After stirring, I wash the mixture with
water to remove the PyBOP and than evaporated the solvent. I found that there are a lot of the DIPEA in my mixture which can not be removed by
evaporating. I did a column but I can not separate the DIPEA, because that it mixed with my compound!Dr. Beaker - 9-1-2008 at 13:54
1. since the b.p of this amine is about 120 it can be removed in RT or gentle heating using good vacuum.
2. if you have no acess to high vacuum remove it by its toluene azeotrope.chemoleo - 9-1-2008 at 16:47
Make the HCl salt of DIPEA and then distill the more volatile compound you are after. Presumably all your amines of your compound are converted to
amide, and will thus not form HCl salts. Or, run HPLC etc etc, I'm sure you can work out something from there.
[Edited on 10-1-2008 by chemoleo]dangator - 27-1-2008 at 20:18
Honestly the easiest way around this problem without knowing the identity of your product is a double column. Amines are never easy to chromatograph
in my experience (I'm assuming you're leaving one amine free); your stuff is just trailing together. MeOH/CHCl3 mixtures work well, and adding a
smidge of concentrated ammonia is a trick that sometimes reduces trailing. It's a non-answer (just do it again) but it'll likely work. I've had
success with nucleic acid derivatives by doing zero workup, quick filter though silica and then column.chemrox - 28-1-2008 at 15:31
I say without more information suggestions here are weak. *Assuming* HCl won't mees up the product that would be my first choice. I'm intrigued by
the above, however and would love to hear more about the double column approach. Also what about rigging sort of a flash column by pushing everything
through with N2 pressure? @dangator: does the ammonia trick work with mixtures it won't dissolve in?Nerro - 7-5-2008 at 06:36
I have a similar problem, I have synthesized something that is a salt and in the reaction mixture there is DiPEA.HCl... Is there any info out the on
the solubility of DiPEA.HCl?Klute - 7-5-2008 at 08:00
You could try basing evrything, and washing with conc. CuSO4 solution. I know this removes triethylamine effectively. Is your other product a amine?
I tried searching if the formation of amine/copper complexes was selective to primary,secondary and/or tertiary , but din't find any info on the
subject.. Anyone knows?Nerro - 7-5-2008 at 08:35
Hmm, that might work. Only I don't really know how I would then proceed to remove the Cu-complex...Klute - 7-5-2008 at 08:52
Well, basify your product, extract it into non polar, and wash the none polar several times with CuS4 solution, then water and finally brine. What is
your product (functions?)Nicodem - 7-5-2008 at 08:58
Diisopropylethylamine is used exactly because the only electrophile/acid that it can react with is a proton and nothing bigger than that, so I
seriously doubt it could ligand something stericaly relatively as bulky as the Cu<sup>2+</sup> cation.
If the amount of DIPE hydrochloride is small, then a recrystallization should be the best option among the simple solutions. This way you would not
have to freebase the salt mixture. If there is a lot of this contaminant, then basifying and isolating the amine mixture followed by drying in vacuo
should do (assuming the product is an amine of considerably higher molecular weight than DIPE). Then, of course, there is also the option of doing a
chromatography on the free base mixture.Klute - 7-5-2008 at 10:04
Hum, good point. I was just guessing by analogy to Et3N, but didn't consider the sterical factor.. Too bad.unionised - 7-5-2008 at 11:12
Is ti more stericly hindered than things like triphenylphosphine?
I think the Cu++ wash is worth a try unless the product you want is very susceptible to oxidation in which case Ni++ might be better.
It's difficult to see this doing much harm.Nicodem - 7-5-2008 at 11:37
Quote:
Originally posted by unionised
Is ti more stericly hindered than things like triphenylphosphine?
Most certainly.
Is triphenylphosphine considered as particularly stericaly hindered? I never heard about it considered that way. I would even tend to believe that
crowding around a phosphorous atom does not influence much its ability to share the lone electron pair even with larger electrophiles/acids/metals. At
least solely by considering that it is one period above nitrogen in the periodic table (which should make its radius big enough to make crowding more
or less irrelevant or at least relatively so).
A quick SciFinder search of quaternized DIPEA compounds yields only the salts of the protonated specie and a single reference for its complex with BH3
(and even this as its use in a patent procedure). Though I could buy it that BH3 might be a small enough acid to combine with DIPEA, I doubt copper or
nickel cations have any interaction.
