Expt 9: The Aldol Condensation

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1 Expt 9: The Aldol Condensation INTRDUCTIN Reactions that form carbon-carbon bonds are particularly important in organic chemistry as they allow the synthesis of more complex structures from simpler molecules. ne of the more common types of these reactions are condensation reactions which occur between carbonyl-containing molecules, in which the enol or enolate of one carbonyl compound acts as the nucleophile, and a second carbonyl compound acts as an electrophile. If the carbonyl compounds are aldehydes or ketones, this process is known as the Aldol condensation. In a self-aldol condensation, the same carbonyl compound condenses with itself, whereas in a mixed-aldol condensation, the two carbonyl compounds are different. In the second case, careful choice of both components is required so that only a single product is formed. Usually one component is selected because it cannot form an enolate, and therefore can only act as the electrophile. These reactions may be catalyzed by either acid or base we will be performing a base-catalyzed reaction using aqueous sodium hydroxide as the base. The reactions we are doing in this lab are sometimes known as the Claisen-Schmidt condensation, which is a mixed-aldol reaction between a ketone and an aldehyde. In our cases, the ketone is acetone, and the aldehyde component is benzaldehyde or p- methoxybenzaldehyde, often known as p-anisaldehyde. f these compounds, only acetone can form an enolate anion, and it will preferentially react with the more reactive carbonyl group of the aldehyde, ensuring that we only get a single product. Acetone contains enolizable sites on both sides of the carbonyl group and thus a second condensation can occur with a second equivalent of benzaldehyde. The summary reactions are shown below: 2 + Na (aq) ethanol C C 3 benzaldehyde dibenzalactone 2 + Na (aq) ethanol C C 3 3 C 3 C C p-anisaldehyde dianisalacetone 3 1

2 EXPERIMENTAL VERVIEW The key intermediates in the mechanism of these Aldol condensations are shown in the scheme below. Deprotonation of acetone with Na generates its enolate anion this enolate anion is in equilibrium with free acetone as the pka of acetone is 19.3 and Na is not a sufficiently strong enough base to ensure complete deprotonation. owever, as benzaldehyde is a more reactive electrophile than acetone, the enolate will selectively act as a nucleophile towards it, forming a β-hydroxyketone intermediate. Both of these steps are reversible, but the β-hydroxyketone readily undergoes favorable dehydration under base-catalyzed conditions to form the α,β-unsaturated ketone product. The more stable trans-alkene is the only product of the dehydration. The reaction will stop at this stage, unless two equivalents of the aldehyde are present, in which case the process repeats itself. The methyl ketone can undergo enolization and reaction with a second equivalent of benzaldehyde forming another β-hydroxyketone, which also spontaneously dehydrates to give the final product, again as the trans isomer. 3 C C 2 Na C C 2 enolate anion 3 C C 2 C 2 enolate anion (resonance not shown) Na C 3 β-hydroxyketone - 2 C 3 α,β-unsaturated ketone Aldol condensation product α,β-unsaturated ketone double Aldol condensation product In the solvent system we are using, aqueous ethanol, the double-aldol product crystallizes out of the reaction mixture and can be recovered by filtration. Washing with water removes traces of Na and the product is recrystallized from ethanol. 2

3 REAGENT/PRDUCT TABLE: Reagents MW (g/mol) MP (ºC) BP (ºC) Density acetone benzaldehyde p-anisaldehyde % Na(aq) (of solute) 1.11 ethanol (95%) Products MW (g/mol) MP (ºC) BP (ºC) Density dibenzalacetone dianisalacetone FR YUR SAFETY: 1.Wear gloves when dispensing reagents. If Na is spilled on the skin, immediately rinse off with plenty of flowing water. 2. Ethanol is highly flammable. Your instructor will assign the aldehyde component you should use in Step 2. therwise, the procedures are the same. EXPERIMENTAL PRCEDURE: 1. btain a clean, dry 5 ml conical reaction vial with a spin vane and add 2 ml of 10% sodium hydroxide solution. Place it in the aluminum heating block on your stirrer/hotplate and commence stirring. Do not heat! 2. Record the mass of a clean, dry small sample vial. Benzaldehyde only: In the hood, dispense 0.20 ml of benzaldehyde into this vial. Reweigh the vial and determine the mass of benzaldehyde you are using. p-anisaldehyde only: In the hood, dispense 0.25 ml of p-anisaldehyde into this vial. Reweigh the vial and determine the mass of p-anisaldehyde you are using. 3. Using a Pasteur pipette, add the aldehyde to the stirring sodium hydroxide solution in the conical vial on your hotplate. Use a small volume (few drops only) of ethanol to wash out the sample vial and add the washings to the conical vial using the same pipette. 3

4 4. In the hood, transfer 1.6 ml of the acetone/ethanol solution to another clean, dry sample vial and return to your bench. [Note: This solution contains 58 mg of acetone in each 1.6 ml of ethanol solution]. 5. At your bench transfer the acetone/ethanol solution to your conical vial containing the other reactants with a Pasteur pipette. Then place a cap loosely on the conical vial. 6. Stir the reaction for 30 minutes at room temperature (No eating!) and make a note of any observations. 7. After 30 minutes, you should have observed solid or crystal formation. Set up your irsch funnel for vacuum filtration. 8. Add 1-2 ml DI (deionized) water to the conical vial until its full and break up any solids in the vial with a microspatula to make them easier to transfer. Then pour the contents of the vial onto the irsch funnel and filter the solid. 9. To ensure complete transfer of all the solids into the irsch funnel, wash out the conical vial with two 3 ml portions of DI water and transfer all washings into the irsch funnel. Turn off the vacuum before each transfer to ensure that the water contacts the solids in the funnel sufficiently to properly wash the solids. 10. Pull vacuum on the crystals for 5 minutes or until they are no longer wet. 11. You need two hot water baths for the recrystallization of your product. First set up one hot water bath using a 50 ml beaker with ~30 ml of water on your hotplate, set to 4. [The water does not need to reach boiling but should be sufficiently hot to cause ethanol to boil.] Then, set up a second hot water bath, next to the first one, using a 100 ml beaker that s half full of water (~50 ml). The small bath will be used for heating the ethanol needed for recrystallization, and the larger bath will be used for keeping the recrystallization solution hot while the crystals are dissolving. 12. btain a clean, dry large sample vial and fill it one-third full with 95% ethanol. Using a micro clamp, clamp it in the smaller water bath and heat until it is boiling. 13. While the ethanol is warming, obtain a weight on your crude crystals. Pre-weigh a 25 ml Erlenmeyer flask, record the weight in your notebook then transfer the crystals to the Erlenmeyer. Re-weigh the Erlenmeyer flask, recording the weight with the crystals, to obtain the mass of the crude crystals. Then, using a Pasteur 4

5 pipette, add ~1 ml of the hot ethanol and swirl to begin dissolving. Clamp this flask in the larger hot water bath to keep the solution hot. 14. Continue adding ethanol in small portions (~1/4 ml at a time) with stirring with a glass stirring rod until all of the crystals just dissolve (you should only need 2-3 ml so do not add too much at one time). 15. Remove the flask from the water bath and allow to cool to room temperature slowly on the benchtop, and then further cool the solution in an ice bath. Crystals should form if not, scratch the bottom of the flask with a glass stirring rod to induce crystallization. 16. Clean your irsch funnel and reassemble the filtration apparatus. nce crystallization appears complete, isolate the crystals by filtration, and wash with one 1 ml portion of ice-cold ethanol. Pull air through for a few minutes to further dry the crystals. 17. Leave the crystals to dry on your filter funnel standing in a small beaker in your locker until next week, when you will obtain a melting point and IR spectrum on your product. After completing the MP and IR, submit your product in a properly labeled SMALL sample vial WASTE DISPSAL 1. The filtrates should be placed in the waste container labeled aqueous basic waste. 2. Carefully wash all the apparatus used in this experiment in the sink and return the glassware and equipment to your lab station. CALCULATINS 1. Calculate the number of moles of aldehyde used (make sure to use the mass of aldehyde and not the volume) 2. Calculate the number of moles of acetone used. 3. Determine which component is the limiting reagent (remember the mole ratio!) 4. Calculate the theoretical yield of your double Aldol condensation product. 5. Calculate the percent yield of your double Aldol condensation product. 5

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