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Re: ORGLIST: NaH reaction

From: Graham Cumming <graham.cumming>
Subject: Re: ORGLIST: NaH reaction
Date: Thu, 28 Jun 2012 11:22:29 +0200
Why, since it has been known for so long (30 years) that NaH/DMF is a
dangerous combination, do people still use it?

NaH and DMF can (not often, but you don´t want to be there if it does)
result in a thermal runaway, with the solvent decomposing to gaseous
products - at best, the potential for a mess in the fumehood, at worst
glass and hot reactants flying across the lab.  While such a runaway
typically happens above 50 degC, calorimetry data shows exothermic
behaviour even at 20 degC.

I´m not aware of incidents on a small scale (is anyone else?) but if
we all stopped using (and publishing) this combination for small scale
reactions, then people would be less tempted to use it later on larger
scales.  Related solvents (NMP, DMA) and DMSO may be less prone, but
can still ´go off´ in the same way.

For your specific reaction, 2-chlorophenol is easy to deprotonate, as
the proton is pretty acidic.  NaH is more than sufficient.  For
alkylation, K2CO3 or Cs2CO3 will normally be enough (DMF at room temp,
or THF or toluene at reflux), and often (at 100 degC or more) is
sufficient for SnAr reaction too, since you have not specified what
your reaction is.

Just to reiterate - do NOT heat NaH/DMF, it is not safe.

With NaH/DMF, the most obvious reason for failure is water - either
your NaH is ´dead´ (the 60% in oil grade should be grey, not white) -
if the bottle is old, this is probably the case.  Also, DMF and
similar solvents are very difficult to dry, and unless you have
specifically done so it is almost certainly too ´wet´ for NaH.  If gas
evolves when you add NaH to DMF without the phenol, this shows it is
wet.  But in any case, NaOH (teh result of water + NaH) is still a
strong enough base to deprotonate 2-chlorphenol.

On 27/06/2012, vinutha hanumaiah <> wrote:
> Hi all,
> Am doing a regioselective reaction with  2- chlorophenol and a substituted
> pyridine in DMF.  It seems the phenol is not deprotonated completely in the
> reaction ending up with less yield. Is it possible to heat the reaction
> mixture? I have never done heating with NaH. Please can anyone suggest me
> anyother strong base for deprotonation of phenol or suggest ideas to
> improve yeilds?
> Thanks,
> Thanu

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