METODE KALKON

GENERAL PROCEDURE FOR THE SYNTHESIS OF CHALCONESa

Reference: Roberts, Gilbert, & Martin, "Experimental Organic Chemistry,"
Saunders, 1994, 543.
Please calculate the amounts you need prior to coming to the lab so you can spend your lab time
doing chemistry rather than calculations!
O
O

CH3

NaOH/EtOH/H2O

+
X

Y
benzaldehyde

acetophenone

chalcone

Dissolve 0.01 mol of the benzaldehyde and 0.01 mol of the acetophenone in 10
mL of 95% ethanol in a 25-mL Erlenmeyer flask equipped with a magnetic stirring
barb. 3.5 mL of 6M NaOH solution are then added to the reaction flask using a
Pasteur pipettte. Stir the reaction mixture for 10 minutes c. Cool in an ice-water
bath until crystal formation is complete. Add 2 mL of ice-cold water to the flask
and vacuum filter. Wash the crystals with 5 mL of water followed by 3-5 mL of icecold ethanol. Allow to air-dry. Recrystallize from 95% ethanol if necessary d.
Notes
a
Not all combinations of substituted benzaldehydes and acetophenones will
result in the simple formation of chalcones. Try figuring out which combinations
should be more reactive.
Some will require longer reaction times (e.g., the
unsubstituted chalcone takes approximately 3 hours and usually forms an oil
rather than crystals. However, a recent JCE article (2000, Vol. 77, p. 511) gives a
method that apparently works. By all means give this variation a try. You can
get the article from the lab web site).
Use TLC to determine the appropriate
reaction time. Some combinations will not work.
b
Some benzaldehydes and acetophenones are not very soluble in ethanol. If this
is the case you can a) use some more ethanol and/or b) warm up the solution.
Since the Aldol condensation is exothermic be careful if adding the NaOH solution
to a warm solution of the carbonyl compounds.
c
Often the chalcone will begin to precipitate before the 10 minutes is up.
However, don't cool until the ten minutes is up. If the chalcone has not begun to
precipitate after 10 minutes, check the progress of the reaction by TLC before
cooling.
Do not throw away the reaction mixture as "no good."
See note a
above.
d
Check the purity of your product by TLC (7:3 hexane/ethyl acetate on silica gel
is a good place to start. Remember to run starting materials on the same plate
as your sample.)

A variety of methods are available for the synthesis of chalcones, the

most convenient method is the one that involves the Claisen-Schmidt
condensation of equimolar quantities of a substituted acetophenone with
substituted aldehydes in the presence of aqueous alcoholic alkali.
10-17
In the
Claisen-Schmidt reaction, the concentration of alkali used, usually ranges
between 10 and 60 %.
18-19
The reaction is carried out at about 50
o
C for 12-15
hours or at room temperature for one week. Under these conditions, the
Cannizaro reaction
20
also takes place and thereby decreases the yield of the
desired product. To avoid the disproportionation of aldehyde in the above
reaction, the use of benzylidene-diacetate in place of aldehyde has been
recommended.
21 (a)