Re: Problem with the Claisen condensation

Marcin Ptaszek wrote:
> 
> Dear Colleagues,
> 
> I have performed reaction of p-hydroxyacetophenone with ethyl acetate,
> in the presence of sodium, in order to obtain p-hydroxybenzoylacetone.
> I have done it according to the analogous procedure for orto-hydroxy
> izomer, which I found in the literature. I have refluxed a mixture of
> ketone, ester and sodium metal, under argon for 4 houers. In
> accordance with the published procedure I have obtain the yellow
> precipitate (probaly the sodim salt of product), but after treatment
> it with 40% acetic acid I have obtain a pure starting material
> (p-hydroxyacetophenone).
> Could anyone give me any suggestion what is wrong.
> Thank you in advance.

Why not make the acetate ester of p-hydroxyacetophenone and react it
with a strong base (e.g., sodamide or K t-butoxide in ether)?  Now
everything is its own protecting group.  Dissolving sodium metal
always makes me worry about reduction side products, though it is
worth a try (maybe with a few mole-% isopropanol to get the ball
rolling).  Dioxane boils where sodium melts.

You might even get away with 2.1 equivalents of powdered KOH in
pyridine around 60-80 C.  Get a good pair of oven mits.  Heat KOH
pellets in a mortar, with the pestle in the oven too, at 110 C for 90
minutes.  Quickly grind it up fine while hot and store the powder in a
tared plastic zip-lock bag.  Set up your reaction, snip the end of the
bag to dispense the KOH right into the pot.  I imagine the whole thing
will dissolve to give a yellow solution that quickly solidifies as the
product dianion precipitates.  Stop the stirrer and keep it warm for
an hour, cool (all under inert gas), and quickly ladle the mush into
vigorously strred ice-cold AcOH solution.

An early "Organic Syntheses" uses the pyr/KOH trick for the reacton of
o-benzoylacetophenone into o-hydroxyphenyl-phenyl-1,3-propanedione. 
This is an optimum case, with no naughty enolizable protons in the
wrong place and a cyclic intramolecular intermediate.

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