Aldol Type Condensations
Aldol Type Condensations on Supported
David A. Nelson
General Procedure for Aldol-Type Condensations Using SPE
Tubes and Ion-Exchange Resins
- Fit a 8 mL SPE reservoir with a closed stopcock and support it
in an appropriate fashion. If the reservoir does not have a frit
in the bottom, insert one. Make sure that the frit is pressed down
- Add about 2 mL (1/4 full) of a strongly basic anion exchange
resin in the hydroxide form to the reservoir. A convenient way to
do this is to make a slurry of the resin in the solvent being used
and use a poly transfer pipet that has had the tip cut back so
that it will suck up and hold the resin slurry.
- Allow the resin to settle. Open the stopcock and allow the
solvent to drain from the tube. If a vacuum system is available,
the solvent can be sucked out and the stopcock closed.
- Mix the reagents to be used in a test tube with 0.5 mL of
solvent (or more if necessary for solution of the starting
materials) and transfer the mixture carefully to the top of the
resin bed in the reservoir with a poly transfer pipet. Wash the
test tube with another 0.5 mL of solvent and add this to the
- If necessary, add solvent until it is about 1-2 mm above the
top of the resin bed. The idea is to have the reaction solution in
contact with the entire resin bed. Agitate gently to mix the
reagent solution. One way of doing this is to insert a 1 mL
calibrated poly transfer pipet to the bottom of the resin bed and
squeeze the bulb slowly. The expelled air bubbles will mix the
reactants. If the resulting solution is much above the resin bed,
cap the tube and shake it occasionally.
- Allow the solution to stand for 30 minutes, or as directed by
- After this time if it appears that product has crystallized in
the reservoir tube add enough solvent to dissolve the product. To
aid in solution the top of the reservoir may be capped and the
- Open the stopcock and allow the contents to drain into a
flask, or suck the contents through with a vacuum device. Wash the
resin with one bed-volume of solvent.
- Analyze the solution to determine the percent conversion of
reactant to product, and/or isolate and purify the product as
directed by your instructor.
- For Chalcone, use 0.5 mmol each of
benzaldehyde and acetophenone.
- For 4-methoxychalcone, use 0.25mmol each of
4-methoxybenzaldehyde and acetophenone. Larger amounts tend to
crystallize in the reservoir. Use 50/50 ethanol/acetonitrile for a
- For Dibenzalacetone, use 0.25 mmol of acetone
and 0.50 mmol of benzaldehyde.
- For Monobenzalacetone, use 0.25 mmol of
benzaldehyde and 2.0 mmole of acetone.
- Amounts for other chalcones have not been optimized. It is
recommended to start with 0.1 mmol each of the substituted
benzaldehyde and substituted acetophenone.
- The liquids are most conveniently measured by volume using a
Safety Considerations: Have available MSDS for
all reactants and solvents used. Assign reading to your students as
required by your institutional safety policies. In general, ethanol
is listed as a flammable liquid and an irritant. Most of the
suggested reactants are listed as irritants. Benzaldehyde has a
cancer suspect rating on the MSDS from Aldrich, and it is listed as
such on the label. Carcinogenicity is based on one rat test; the
mouse test was negative. There is no evidence of human toxicity. The
FDA allows the use of benzaldehyde as a food additive. Artificial
almond flavor is 65% benzaldehyde and 35% alcohol. Other suppliers
usually list it as a toxic irritant. If you need to avoid the
potential carcinogenicity, use a substituted benzaldehyde. If
appropriate, the use of benzaldehyde can serve as an example of how
to handle a carcinogenic substance in the lab. As a minimum this
entails goggles, gloves, and lab coats, and the use of a "Designated
Area". The hydroxide ion exchange resins are listed as eye irritants,
but are much less hazardous than the concentrated NaOH solutions used
in solution methods. If you convert the chloride form of the resin,
aqueous NaOH will be required. It is recommended that the conversion
be done by lab assistants or the faculty in charge. Ethanol is a
toxic, flammable liquid.
Waste Disposal Considerations: The used ion
exchange resins can be recycled and should not be considered as
waste. As part of the procedure students can be instructed to empty
the resins into a specific container containing 1N NaOH. This will
regenerate any ion exchange sites that may have been exchanged. The
most probable cause of the exchange is the formation of the benzoate
anion resulting from aldehyde oxidation. Some reactants seem to
discolor the resins but that should not affect their behavior as
catalysts. After a sufficient amount of catalyst is recovered it
should be filtered on a sintered glass funnel, washed to neutrality,
and used again.
The SPE reservoirs, frits, and stopcocks can be used repeatedly.
Leave the frit in the reservoirs and wash them with a small amount of
ethanol. The only waste from this procedure should be the ethanol or
other solvents used for recrystallizations.
General Procedure for "Dry Media" Aldol Condensations
- Prepare the KOH/Alumina by dissolving 1.0 g of potassium
hydroxide in 100 mL of methanol, and adding 10.0 g of neutral
Activity Grade I chromatographic alumina. Scale up as necessary
allowing 1.0 g of supported reagent for each experiment. Evaporate
the slurry using a rotary evaporator at about 90 degrees for 1 hr
with water aspirator vacuum. A free flowing powder containing
about 5% residual methanol should result.
- Fit a 8 mL SPE reservoir tube with a frit and stopcock and add
1 g of the supported reagent.
- Dissolve 0.25 mmol of each reactant in 0.1 mL of MTBE (or
other non-polar solvent) and add the solution onto the KOH/alumina
reagent in the SPE tube. Liquid reactants can be added directly
with no solvent.
- Cap or stopper the SPE tube and rotate it until the reactants
appear evenly distributed on the alumina. This may take several
minutes. No lumps should be evident. If a color begins to form,
this should appear evenly distributed over the alumina.
- Rotate the tube periodically during the course of the
- After the reaction period is complete, wash the product from
the support by adding at least 2 mL of MTBE or other non-polar
solvent to the tube, placing a test-tube under the stopcock, and
opening the stopcock. This is equivalent to eluting a small-scale
chromatography column. It is convenient to use a vacuum device for
this step. If the product is colored, the elution can be followed
by observing the loss of color of the support. Colored by-products
are usually formed in these condensations which are more strongly
held than the desired product. Methanol or ethanol will wash the
KOH off the support.
- The purity of the eluted product can be followed using TLC or
HPLC if available.
- If product isolation is desired, evaporate the elution solvent
and recrystrallize the product from the appropriate solvent.
Reaction Times: Yields of dry-media reactions
vary considerably. Yields of 60-80% are usually obtained in 2-3 hrs.
Reaction can remain for longer periods of time, up to one week, but
often side products increase. To improve yields allow the reactants
to sit as long as possible during the lab period and then elute the
product; work it up next period if that is desired. "Overnight" or 24
hr seems to be an optimum time for complete reaction to take place.
It is important that the aldehydes used be free of any
corresponding acids. We routinely shake benzaldehyde or liquid
substituted benzaldehydes with bicarbonate solution before use. Solid
substituted benzaldehydes should be recrystallized or otherwise
purified to remove any suspected acid impurities.
The resin used for Aldol Condensations is Amberlite IRA-400 (OH)
which may be purchased from Aldrich. Wash the resin several times in
the solvent to be used before running the reaction. SPE tubes with 8
ml reservoirs, frits and stopcocks may be purchased from Alltech.
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© February 1996.
These experiments are designed to be
used in college and university level chemistry laboratory courses,
and assume the availability of routine supplies, equipment, and
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