An aldol condensation reaction was performed on acetophenone using p-anisaldehyde and sodium hydroxide as a base. This produced trans-p-anisalacetophenone in the form of a fluffy yellow crystal. The reaction was performed in a test tube and sodium hydroxide was added drop by drop followed by recrystallization and vacuum filtration. In order to verify the presence of the ketone 2,4-dinitrophenylhydrazone was synthesized and reacted with trans-p-anisalacetophenone resulting in a red color change indicating the presence of the ketone. The percent yield of the product was found to be 49% with six NMR shifts at 1.76, 2.14, 3.83, 6.98, 7.53, and 7.97 ppm. The melting point was originally found to be 169.7-180.1 °C but was determined to be an error. Introduction:
In this experiment an acetophenone is treated with Sodium hydroxide to produce an enolate (Figure 2).
Enolates are a resonance stabilized intermediate that have the ability to attack as an electrophile due to its two nucleophilic sites1. The base chosen for this reaction is important as it must be strong enough to drive the reaction forward1.
The enolate intermediate allows acetophenone to react with p-anisaldehyde to produce an aldol which then can undergo aldol condensation by using the alcohol as a leaving group (Figure 3) to produce a α,β-unsaturated ketone such as the product in this experiment: trans-p-anisalacetophenone1. The major product of an aldol condensation is usually observed as a trans product as it provides less steric hindrance due to the substituents on each side of the alkene being placed farther apart1. 2,4-dinitrophenylhydrazine is also used in this experiment to indicate the presence of a ketone. When hydrazine is reacted with a ketone in acidic conditions it produces 2,4-dinitrophenylhydrazone which is a bright red color2. Thus, 2,4-dinitrophenylhydrazine can be used as an indicator test for the presence of ketones. Recrystallization is also performed in this experiment as it provides a means to purify solids by cooling a saturated solution down to where the solid will precipitate out of its solvent. Discussion:
An aldol condensation reaction was performed creating trans-p-anisalacetophenone by using both acetophenone and p-anisaldehyde (Figure 4).
A small amount of acetophenone and p-anisaldehyde were placed into a test tube with ethanol. This solution was shaken until all solid was dissolved. A 50% sodium hydroxide was produced with water and cooled to room temperature. Five drops of this hydroxide solution was added to the test tube and shaken to produce a dark yellow liquid before being cooled in an ice bath. This caused yellow crystals to be recrystallized out of the solution into the bottom of the flask. They were then vacuum filtrated and recrystallized again from methanol to produce a very fluffy yellow crystal product. The indicator used to determine the presence of ketones 2,4-dinitrophenylhydrazone was produced by fist mixing a solution of sulfuric acid and 2,4-dinitrophenylhydrazine with water and ethanol (Figure 5). Furthermore, this mixture was then mixed with the product trans-p-anisalacetophenone in ethanol and recrystallized from ethanol producing red crystals.
The resulting trans-p-anisalacetophenone was found to have a percent yield of 49% with the limiting reagent being p-anisaldehyde. This yield was reasonable as only 1 gram of the product could have been produced overall, but it could have been higher with more refined techniques as some crystal was lost on the filter paper and when transferring to a watch glass for weighing. The product can be identified as trans-p-anisalacetophenone as the NMR data recorded matches the literature NMR for the product with peaks near 8 ppm and 4 ppm with the exception of a peak at 2.14 ppm which was due to acetone being present in the product. The indicator used also indicated the presence of a ketone which is also present in trans-p-anisalacetophenone. But the product can be determined as impure as the NMR integration does not match well with the literature values and the presence of acetone. Also, the recorded melting point of 169.7-180 °C cannot be used as the red crystals from the 2,4-dinitrophenylhydrazone indication were used instead of the normal yellow trans-p-anisalacetophenone crystals. If the normal crystals were used the melting point would have been closer to the literature melting point of 73-76 °C. Conclusion:
Overall, a yellow fluffy crystal solid was created from the aldol condensation reaction from acetophenone and p-anisaldehyde. The solid was identified as trans-p-anisalacetophenone by comparing its NMR to literature NMR data, which also showed that the resulting product was impure. 2,4-dinitrophenylhydrazone was used as an indicator to determine the presence of a ketone in the product. The melting point determination as incorrectly performed. In the future more caution will be used for which products need to be used for melting points but being rushed does not help with clear thinking. The reaction could likely be improved by using a rotary evaporator to produce a higher percent yield of the product. Experimental:
All reagents (p-anisaldehyde, Acetophenone, sodium hydroxide, sulfuric acid, 2,4-dinitrophenylhydrazine, ethanol, methanol, and water) used were obtained from the reagent hood and all glassware used was obtained from the provided glassware kits. Reagents were not further modified unless written. 50% sodium hydroxide solution was produced from 1g sodium hydroxide per 1 ml of water. Vacuum filtration was performed with a filter paper. Melting points were determined by a SRS DigiMelt MPA160. NMR was recorded through a Nanalysis NMReady 60. Trans-p-anisalacetophenone. A solution of p-anisaldehyde (0.98 ml) and acetophenone (1.03 ml) was mixed with ethanol (3.10 ml) in a test tube and shaken until dissolution.. 50% sodium hydroxide (5 drops) was reacted drop-wise and solution was shaken producing yellow liquid. Solution was cooled with ice-bath and yellow crystals formed. Crystals were vacuum filtrated and recrystallized with methanol. Product was dissolved in ethanol (20 ml) reacted with 2,4-dinitrophenylhydrazine (0.405 g) solution (15 ml) containing sulfuric acid (1.95 ml), water (3.0 ml), 2,4-dinitrophenylhydrazine (0.405 g), and ethanol (10 ml). Mixture was shaken and a solid formed after turning red. Solid was vacuum filtrated and recrystallized out of ethanol. Trans-p-anisalacetophenone (0.528 g, 49%, 169.7-180.1 °C). NMR: (60 MHz, Chloroform-d) 1.76, 2.14, 3.83, 6.98, 7.53, 7.97 ppm). References:
Gilbert, John C., Stephen F. Martin, and Royston M. Roberts. Experimental Organic Chemistry: A Miniscale and Microscale Approach. 5th ed. Fort Worth: Saunders College Pub., 1998. Print. Klein, David R. " Alpha Carbon Chemistry: Enols and Enolates" Organic Chemistry. 1st ed. Hoboken, NJ: John Wiley, 2012. 1030-1089. Print.