Getting rid of DMF

[Brian Watson]

Compared to THF, I've found that getting rid of DMF is a major ass-pain.
For
one thing, one can often remove the bulk of THF from the crude product by
rotovap before partitioning before washing out the remaining THF with water.

DMF on the other hand is too high boiling to rotovap, it seems to partition
less into the aqueous phase than THF, and traces of DMF remaining in an oil
or
resin are all but impossible to remove in vacuo.

I've tried using a mixture of ether and hexane for the organic phase of the
aqueous work-up, and this works ok. But any tricks readers are familiar
with
would be appreciated.

--
Paul J. Franklin (moderator - sci.chem.organic.synthesis)
http://chemistry.gsu.edu/post_docs/koen/wnewshp.html
Georgia State University <che...@panther.gsu.edu>
Atlanta, GA

[Gabriel Tojo]

Brian Watson wrote:

> Compared to THF, I've found that getting rid of DMF is a major ass-pain.
> For
> one thing, one can often remove the bulk of THF from the crude product by
> rotovap before partitioning before washing out the remaining THF with water.
>
> DMF on the other hand is too high boiling to rotovap, it seems to partition
> less into the aqueous phase than THF, and traces of DMF remaining in an oil
> or
> resin are all but impossible to remove in vacuo.
>
> I've tried using a mixture of ether and hexane for the organic phase of the
> aqueous work-up, and this works ok. But any tricks readers are familiar
> with
> would be appreciated.
>

In case of doubt, THF is the solvent of choice for all the reasons you mention.
The problem is that DMF is a superb dipolar aprotic solvent which works fine in
most SN2 reactions involving heteronucleophiles. In many cases those reactions
go much quicker in DMF. The alternative of DMSO suffers from tendency to cause
unwanted oxidations.

The best elaboration for a reaction done in DMF is the following:

1?Add very slowly water to the reaction mixture.
2?When some precipitate appears, heat gently till it disolves.
3?Keep on adding water and heating till the hot solution is not able to acept
more water without precipitation of the product.
4-Leave the hot solution overnight.
5?Hopefully the following day you will have some fine crystals.
6-Filter the crystals and wash them with water.

The success of this elaboration depends on the willingness of the product to
crystalize

Best regards.

--
Gabriel Tojo

Profesor Titular de Química Orgánica
Faculty of Chemistry
University of Santiago de Compostela
SPAIN

[peter.breed]

Brian Watson wrote:

> Compared to THF, I've found that getting rid of DMF is a major ass-pain.
> For
> one thing, one can often remove the bulk of THF from the crude product by
> rotovap before partitioning before washing out the remaining THF with
> water.

> DMF on the other hand is too high boiling to rotovap, it seems to
> partition less into the aqueous phase than THF, and traces of DMF
> remaining in an oil or
> resin are all but impossible to remove in vacuo.

> I've tried using a mixture of ether and hexane for the organic phase of
> the
> aqueous work-up, and this works ok. But any tricks readers are familiar
> with
> would be appreciated.
>

I usually find that partitioning between ether and saturated brine is good
for removing DMF, it sometimes takes 3-6 brine washes, of course it depends
how much was in there to start with. Its easier if you can remove most of
the DMF on a well setup rotavap first. We have one with a dry ice trap, and
one of our better pumps which we normally use for smellies, this usually
get rid of most. it helps using a splash head, as one DMF tends to bump,
and the DMF often collects in the splash head, as it does need to travel to
far. Don't be afraid to turn the bath temp up to 60deg C if your compound
isn't too thermall sensitive
As for resins I have never seen any DMF when I have used my usual 3x
alternating washes with DCM and methanol, though some people argue this can
damage the resin by osmotic shock.
Hope this help
Peter Breed
PS At least you are not using N-methylpyrolidinone, which is even higher
boiling, and harder to remove by extraction

[Jonas Nilsson]

I can't see why you should need to do extaction after evaporating THF. THF
is a very volatile solvent and I have never seen any trace of THF after
rotavap/vacuum pump. I even doubt that any remaining trace of THF would be
extracted by water from most solvents. On the other hand DMF is extractable
by water to my knoledge. If you use a very unpolar organic phase (hexane) it
should be extracted to the aqueous phase. You have to use a lot of
extractions however to get rid of it.

In our lab we evaporate the DMF. You have to use a good pump (oil pump) with
a pressure below 1 mmHg i think to get it to work. Just connect the pump via
a solvent trap emerged in liquid nitrogen or other cooling fluid and then to
your flask containing the solution. Use magnetic stirrer to avoid bumping.
Our pump gets down to 0.2 mmHG, and DMF is evaporated in less than 5 minutes
(<50 ml DMF).

/jN

--
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"Brian Watson" <brian...@MailAndNews.com> wrote in message
news:93coj7$s...@panther.Gsu.EDU...

> Compared to THF, I've found that getting rid of DMF is a major ass-pain.
> For
> one thing, one can often remove the bulk of THF from the crude product by
> rotovap before partitioning before washing out the remaining THF with
water.
>
> DMF on the other hand is too high boiling to rotovap, it seems to
partition
> less into the aqueous phase than THF, and traces of DMF remaining in an
oil
> or
> resin are all but impossible to remove in vacuo.
>
> I've tried using a mixture of ether and hexane for the organic phase of
the
> aqueous work-up, and this works ok. But any tricks readers are familiar
> with
> would be appreciated.
>

[Thomas Hoeg-Jensen]

Yes, I agree that DMF is difficult to remove.
However, it can be removed on rotavapor (mostly).
If you have a good pump, you can do this without much heating, e.g 30-40 oC.

Often it is sugested to replace poisonous DMF with NMP (N-methylpyrrolidone)
I tried removing that on occations, and stay happy with DMF ...

Thomas Hoeg-Jensen, Denmark

[Patrice Gill]

You can try either 2N NH4OH or 2N LiBr they both work rather well. Try using 3X
the volume of aq. phase versus the organic.