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
O
H
CH 3
NaOH/EtOH/H2O
+
X
Y
Y
benzaldehyde
acetophenone
X
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 bar b. 3.5 mL of 6M
NaOH solution are then added to the reaction flask using a Pasteur pipettte. Stir the reaction
mixture for 10 minutesc. 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 ice-cold ethanol. Allow to air-dry. Recrystallize from 95% ethanol if
necessaryd.
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.)