Natural Science Forum / Chemistry / Organic Synthesis / November 2003

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.

How much sodium?  One would expect the phenol group to mop up an equivalent
amount of base, so a second equivalent is needed for the condensation.

Hi Marcin,

the problem which you encountered, is an old topic. The reason is due
to the unprotected phenolic hydroxyl group, since due to tautomerism
this reaction does not takes place.
But to obtain successfully your target molecule, you have to do this
reaction after you have protected the phenolic hydroxyl group. Then
the reaction will work. See the following patent: Thorton, D.A.; et
al: US Patent Appl.
US 3,281,493 (also as corresponding British Patent GB 948,494). This
patent is cited in Chem. Abstr. Vol. 60, 1964, 11950h.

Steven