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Chemistry Forums for Students => Organic Chemistry Forum => Organic Chemistry Forum for Graduate Students and Professionals => Topic started by: reflux on May 23, 2012, 11:57:33 AM

Title: Removal of tetrabutylammonium impurities
Post by: reflux on May 23, 2012, 11:57:33 AM
What are the best ways to remove tetrabutylammonium impurities after a reaction with TBAF, TBAI, etc.  I have a polar amino acid compound which after purification by silica gel column (10% MeOH/DCM) or reverse-phase HPLC (30-70% MeCN/H2O + 0.1% NH4OH) still contains a lot of some tetrabutylammonium impurity (probably as the hydroxide).  It comes from a TBAF mediated OTBS deprotection that requires 3 eq of TBAF, which is why I get so much of the impurity.
Title: Re: Removal of tetrabutylammonium impurities
Post by: discodermolide on May 23, 2012, 01:49:50 PM
Quote from: reflux on May 23, 2012, 11:57:33 AM
What are the best ways to remove tetrabutylammonium impurities after a reaction with TBAF, TBAI, etc.  I have a polar amino acid compound which after purification by silica gel column (10% MeOH/DCM) or reverse-phase HPLC (30-70% MeCN/H2O + 0.1% NH4OH) still contains a lot of some tetrabutylammonium impurity (probably as the hydroxide).  It comes from a TBAF mediated OTBS deprotection that requires 3 eq of TBAF, which is why I get so much of the impurity.


Try an ion exchange resin?
Title: Re: Removal of tetrabutylammonium impurities
Post by: nox on May 23, 2012, 09:14:09 PM
Is your polar amino acid soluble in water? I used to have the same problem when working with unprotected sugars, always had a lot of tetrabutylammonium crap in my aqueous phase which I couldn't get rid of no matter how many organic washes I did.

One thing I found that worked really nicely is via anion exchange with potassium hexafluorophosphate (KPF6). After the reaction I just throw in 3 equivalents of KPF6, this makes a nice and greasy Bu4N+ -PF6 ion pair which dissolves very well in DCM. Wash the aqueous layer with DCM a few times and it cleanly removes all the tetrabutylammonium salts.
Title: Re: Removal of tetrabutylammonium impurities
Post by: Babcock_Hall on May 24, 2012, 06:51:19 PM
Amino acids are eluted from Dowex 50 with ca. 3 M ammonia but a tetrabutylammonium ion should remain bound.
Title: Re: Removal of tetrabutylammonium impurities
Post by: g-bones on May 25, 2012, 07:15:43 PM
maybe deprotect differently? 1% HCl in MeOH typically drops TBS groups like their hot.  MeOH is volatile and you can isolate the HCl salt of your amine.
Title: Re: Removal of tetrabutylammonium impurities
Post by: reflux on June 13, 2012, 11:31:39 AM
Sorry for my late response.  These are all excellent suggestions.  I have a feeling many people dealing with this problem will benefit from this discussion.  I only have ~1-5 mg of material so I haven't been able to try these strategies myself, but I will once I have more in hand.

Thanks to all!