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Topic: best way to remove dimethylformamide  (Read 42783 times)

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Offline Babcock_Hall

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best way to remove dimethylformamide
« on: July 18, 2012, 12:55:57 PM »
What is the best way to remove dimethylformamide (DMF) from a reaction mixture?  The product is an amide that also has an ester and a BOC group.  One suggestion we were given was to add water repeatedly and rotovap the mixed solvent with a Buchi V-500 pump.  Another possibility is to use a high vacuum and a cold trap, and a third would be to use a high vacuum attached to a rotary evaporator.  Thanks in advance.

Offline discodermolide

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Re: best way to remove dimethylformamide
« Reply #1 on: July 18, 2012, 01:02:27 PM »
What is the best way to remove dimethylformamide (DMF) from a reaction mixture?  The product is an amide that also has an ester and a BOC group.  One suggestion we were given was to add water repeatedly and rotovap the mixed solvent with a Buchi V-500 pump.  Another possibility is to use a high vacuum and a cold trap, and a third would be to use a high vacuum attached to a rotary evaporator.  Thanks in advance.

It's BPt. at normal pressure is 152-154°C. So it should come off in a rotavap with a vacuum pump. Bath temperature 30°C if you use high vac.
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Offline fledarmus

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Re: best way to remove dimethylformamide
« Reply #2 on: July 18, 2012, 01:56:33 PM »
If your compound dissolves in ethyl acetate or ether, extraction is by far the best and fastest method. In my experience, DMF is difficult to remove from reaction mixtures. And leaves a very obvious signal in the NMR even in trace amounts.


Offline Dan

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Re: best way to remove dimethylformamide
« Reply #3 on: July 18, 2012, 04:15:48 PM »
I always wash it out. Typically I partition the DMF solution between EtOAc and 1:1 brine/water, drain off the aqueous and wash the organic with 1:1 brine water 3 times, then once with brine. The purpose of the brine in the 1:1 brine/water is to reduce the amount of organic product that gets pulled into the aqueous - you can TLC the aqueous layer from the first extraction to ascertain whether or not this is a problem for your product. If it's quite polar you will probably lose some material, but in my experience the sacrifice is worth it. You can also remove most of the DMF under vacuum and then wash out the last traces.

If you back extract the aqueous with EtOAc you will back extract the DMF, so don't do that unless you are losing a significant amount of product in the wash and have a high vac or other alternative method to remove the DMF.

You can find examples of this method in this paper.
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Offline zoork34

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Re: best way to remove dimethylformamide
« Reply #4 on: July 26, 2012, 02:01:21 PM »
See the link on this page entitled "Efficient extraction of highly polar solvents (i.e. DMF or DMSO) from reaction mixtures - Contributed by Professor Philip Hultin"

http://chem.chem.rochester.edu/~nvd/magicformulas.html

Haven't tried it myself, but it seems useful. 

Offline superg

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Re: best way to remove dimethylformamide
« Reply #5 on: July 31, 2012, 07:09:40 AM »
maybe a bit late to reply, but this might be useful for other peoples...

I have run quite a lot of reactions in DMF and basically used two ways to remove it. The first one was to pour my reaction mixture in water, extract with ether or ethylacetate my compound and wash with water (at least three time). In some cases the compounds was precipitating in water, so just collecting it on a frit, washing of the solid with water. In these case, a simple recryst was enough to get my compound pure and free of DMF.

the second option I used was to remove the DMF by bulb to buld distillation ( bath at 60°C, oil pump vacuum) and trapping the DMF into a liquid nitrogen cooled trap. I tried on a rotavap but it was not convenient. the residue was then dissolved into ether or ethylacetate and washed extensively with water.

note that my compounds were neither volatiles or water soluble.

Offline NotExactly

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Re: best way to remove dimethylformamide
« Reply #6 on: October 02, 2012, 05:16:04 PM »
A great trick to remove DMF via extraction is to wash your organic layer with an aqueous LiCl solution.  I generally use a 1M solution.  This is part of every workup I do for reactions in which DMF is the solvent.  I believe the reason is that the lithium coordinates between the carbonyl oxygen and nitrogen of DMF and pulls it into the aqueous layer. 

I've also heard of people using a lyopholizer to get rid of DMF but I'd imagine this is not so great for the pump. 

Offline metallocene2015

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Re: best way to remove dimethylformamide
« Reply #7 on: January 09, 2015, 08:46:40 AM »
A great trick to remove DMF via extraction is to wash your organic layer with an aqueous LiCl solution.  I generally use a 1M solution.  This is part of every workup I do for reactions in which DMF is the solvent.  I believe the reason is that the lithium coordinates between the carbonyl oxygen and nitrogen of DMF and pulls it into the aqueous layer. 

I've also heard of people using a lyopholizer to get rid of DMF but I'd imagine this is not so great for the pump.

Would this still work if my product also has carbonyls and amines ?

Offline zuriel

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Re: best way to remove dimethylformamide
« Reply #8 on: January 28, 2015, 07:52:47 PM »
A great trick to remove DMF via extraction is to wash your organic layer with an aqueous LiCl solution.  I generally use a 1M solution.  This is part of every workup I do for reactions in which DMF is the solvent.  I believe the reason is that the lithium coordinates between the carbonyl oxygen and nitrogen of DMF and pulls it into the aqueous layer. 

I've also heard of people using a lyopholizer to get rid of DMF but I'd imagine this is not so great for the pump.

Glad this topic has been brought back to life purely for this suggestion! I'm going to try this sometime. Thanks NotExactly.

Offline Babcock_Hall

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Re: best way to remove dimethylformamide
« Reply #9 on: January 28, 2015, 10:25:40 PM »
I think our compound is somewhat soluble in water.  We obtain low recovery when we attempt purification via extraction, and there are functional groups such as a carboxylic acid that give it more polarity than it would otherwise have.  However, I see no harm in trying the LiCl method the next time we do this synthesis.

Offline TheUnassuming

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Re: best way to remove dimethylformamide
« Reply #10 on: January 29, 2015, 09:33:52 AM »
I've always had luck with just rotovap'ing it off with the highvac attached.  Are you wanting to carry directly to the next step or are you going to chromatograph the compound and just want the DMF off before you load?
When in doubt, avoid the Stille coupling.

Offline Babcock_Hall

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Re: best way to remove dimethylformamide
« Reply #11 on: January 29, 2015, 09:46:23 AM »
We run a silica column at this point.

Offline TheUnassuming

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Re: best way to remove dimethylformamide
« Reply #12 on: January 29, 2015, 12:42:11 PM »
I should really look at the time stamp for the original post!  I didn't notice it was resurrected from 3 years ago!
When in doubt, avoid the Stille coupling.

Offline tomek

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Re: best way to remove dimethylformamide
« Reply #13 on: March 13, 2015, 04:05:38 PM »
Don't forget that blowing it out works nicely too. That of course can be time consuming if you're dealing with large amount of DMF (and also not very economical). Recently when in need of removing DMF from the reaction I set up a vial on a hot plate (50°C) and used a stream of argon. It took something over an hour to remove 5 ml of DMF.

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