CH 2280
GREEN CHEMISTRY: SYNTHESIS OF DISUBSTITUTED CHALCONES
– THE ALDOL REACTION (Adapted from a procedure by J. R. Mohrig, C. N. Hammond, and
P. F. Schatz.)
Materials
From the Chemicals Hood:
4-Methylbenzaldehyde
4-Methoxybenzaldehyde
4-Chlorobenzaldehyde
4-Benzyloxybenzaldehyde
4-Methylacetophenone
Nothing from the Stockroom
4-Methoxyacetophenone
4-Fluoroacetophenone
30% Sodium hydroxide aqueous
solution
Ethanol
Scenario:
You will synthesize a disubstituted chalcone and use a variety of analytical techniques to discover which
of its functional groups are reduced by catalytic hydrogenation.
Most research in organic chemistry involves multifunctional molecules. Indeed, most organic
compounds found in nature, as well as modern pharmaceutical agents, are multifunctional molecules.
Determining which functional groups react in a chemical reaction is critical to the success of synthetic
organic chemistry. Another goal of organic synthesis is to discover environmentally friendly reactions,
called green chemistry, where a minimum of waste is produced and the reactions have high atom
economy.
One of the goals of green chemistry is the use of less hazardous solvents. The synthesis of
chalcones can even be done with no solvent. However, the use of water as a solvent leads to a more
uniform product. This straightforward synthesis demonstrates the important chemistry of the aldol
condensation followed by dehydration to form a conjugated ketone. Chalcones are an important class of
naturally occurring compounds of interest to the pharmaceutical industry for their potential antitumor,
antibacterial, antifungal, and anti-inflammatory activity.
A set of chalcones will be synthesized in this project, using a variety of para-substituted
benzaldehydes and acetophenones. After purification by recrystallization and characterization by melting
point, infrared and NMR spectroscopy, the chalcones will be readily identifiable.
SAFETY INFORMATION
Wear gloves while conducting this experiment.
The aldehydes and ketones used in this project are skin and eye irritants.
The concentrated aqueous sodium hydroxide solution is corrosive. Contact with it can cause burns.
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R1
Name
R2
Name
Chalcone
mp, °C
CH3
4-Methylbenzaldehyde
CH3
4-Methylacetophenone
1
126-127.5
OCH3
4-Methoxybenzaldehyde
OCH3
4-Methoxyacetophenone
2
100-101.5
CH3
4-Methylbenzaldehyde
OCH3
4-Methoxyacetophenone
3
127-127.5
CH3
4-Methylbenzaldehyde
F
4-Fluoroacetophenone
4
146-147.5
Cl
4-Chlorobenzaldehyde
CH3
4-Methylacetophenone
5
146-147.5
Cl
4-Chlorobenzaldehyde
OCH3
4-Methoxyacetophenone
6
127-128.5
Cl
4-Chlorobenzaldehyde
F
4-Fluoroacetophenone
7
136-137
C6H5CH2O
4-Benzyloxybenzaldehyde
CH3
4-Methylacetophenone
8
108-109
C6H5CH2O
4-Benzyloxybenzaldehyde
OCH3
4-Methoxyacetophenone
9
116-117
Techniques:
Recrystallization
Melting Point
Infrared Spectroscopy NMR Spectroscopy
Procedure:
Your group will be assigned an aldehyde and a ketone to use in your chalcone synthesis. Combine 14.0
mmol of your aldehyde and 14.0 mmol of your ketone in a 50-mL Erlenmeyer flask. Stir the mixture with
a glass rod until a homogeneous liquid forms.
Add 4 mL of 30% aqueous NaOH to the Erlenmeyer flask. The best way to do this is to pour a
very small amount of this solution into a beaker, then use a plastic disposable pipet to transfer 1 mL at a
time into the Erlenmeyer flask containing the aldehyde/ketone mixture. Pour any left over NaOH solution
into the “Base Waste” 5-gallon waste container in the hood.
Stir the contents of the Erlenmeyer flask occasionally with a stirring rod for 10 min or until the
mixture solidifies. Next, heat the mixture on a steam bath for 15 min. The mixture may liquefy upon
heating.
Cool the reaction mixture to room temperature. If the product does not solidify in 5 min, stir the
mixture while cooling it in an ice-water bath. If solidification does not occur by cooling and stirring, add
1 mL of ethanol to the crude product and stir to induce crystallization. If solidification still does not occur,
heat the product on the steam bath. If the reaction mixture is completely solidified, add 5 mL of water
and stir it with a stirring rod until a suspension forms.
Collect the product by vacuum filtration, and while the vacuum is still connected wash the
product with 20 mL of water. Transfer the solid into a 125 mL Erlenmeyer flask and recrystallize the
crude product from ethanol.
Allow the product to dry until the next lab period, and then obtain its mass and melting point.
Compare the melting point with the literature value listed above. Calculate your percent yield. Obtain an
infrared spectrum and NMR spectrum of the purified chalcone. Save the remainder of your product for
next week’s hydrogenation.
Cleanup: Discard the filtrate from the reaction mixture in the container labeled “Base Waste.” If your
chalcone does not contain chlorine or fluorine, place the recrystallization filtrate in the container for
flammable organic waste; use the container for halogenated organic waste if your chalcone contains
chlorine or fluorine.
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