Aldol Condensation Reaction of 4-chlorobenzaldehyde and 4-methoxyacetophenone Phillip Wachowiak Section 156 Jacob Geri Fall 2013

Introduction The aldol condensation reaction occurs when an enol reacts with a carbonyl compound to form beta-hydroxy aldehydes or beta-hydroxy ketones by self condensations or mixed condensations of aldehydes and ketones as well as other reactions. The Claisen-Schmidt condensation is a specific type of aldol condensation.1 All possible products of the experiment were chalcones, which are an aromatic ketone and enone. Chalcones are important biological compounds, and there is evidence that they can be used as potential antimalarials on bacteria resistant to existing malaria antibiotics.2 The experiment synthesized 4-chlorobenzaldehyde and 4-methoxyacetophenone by aldol condensation to a chalcone product. 4-chlorobenzaldehyde consists of a an aldehyde with a phenyl as the R group and a chlorine atom at the para position, while 4-methoxyacetophenone (acetanisole) has one methyl group and the other group is a phenyl group with a methoxy group at the para position; it has been shown to limit activity of spores and cells of the toxic clostridium botulinum.3 The mechanism of the reaction involves the following steps. A proton on the carbon on the non-phenyl R group of the ketone is deprotonated. This deprotonated form attacks the carbonyl carbon of the aldehyde via nucleophilic addition. A series of protonations and deprotonations leads to the re-formation of the carbonyl as well as an alkene. The recrystallized product of the reaction between acetanisole and 4chlorobenzaldehyde was analyzed using IR spectroscopy, thin layer chromatography, and melting point. Reaction Scheme: (See End) Experimental First, 4-chlorobenzaldehyde (142 mg, 1.01 mmol) was placed into a conical vial equipped with a magnetic spin vain. Roughly one molar equivalent of 4methoxyacetophenone (154 mg, 1.03 mmol) and 1 mL 95% ethanol was added to the vial and stirred. After the compound dissolved, 0.10 mL of 50% w/w aqueous sodium
1 2

Nielsen, A. T. and Houlihan, W. J. 2011. The Aldol Condensation. Organic Reactions. 1438 Li, Rongshi, Kenyon, George L., ET. al. 1995. In Vitro Antimalarial Activity of Chalcones and Their Derivatives 3 Bowles, Bobby L., and Arthur J. Miller. "Antibotulinal properties of selected aromatic and aliphatic ketones." Journal of food protection 56.9 (1993): 795-800.

hydroxide was added to the vial. The vial was capped and stirred at room temperature until it solidified. Chalcone product precipitated out of the solution and was broken up with a spatula. Resultant mixture was diluted with 6 mL ice water. The mixture was stirred thoroughly, and then vacuum filtered and recrystallized. Melting point was 132C, IR 2840, 1655, 1601 , TLC Rf = 0.867 (1:1 ethyl acetate, hexane), 0.596 1:3 ethyl acetate, hexane), 0.318 (1:9 ethyl acetate, hexane), 0.043 (hexane), crude yield was 91.0% and pure yield was 74.1%. Results/Discussion The 4-chlorobenzaldehye was successfully synthesized with 4methoxyacetophenone to form a chalcone product. Qualitative information from the experiment was observed and the IR spectrum data was analyzed for functional groups and structures. TLC and melting point was also analyzed for the product. Both reactants were solids in the form of white crystals that had to be broken up in solution before being fine enough to dissolve. The product of the reaction was a fine white crystalline powder. All aspects of the experiment followed the procedure except for dilution with water, where more water was added with the knowledge that it would be filtered out through vacuum filtration. Additionally, the molar amounts of each reaction had to be calculated based on the actual amount measured. Literature melting point data for the chalcone product is 130-131C. The recrystallized form of the experimental product had a melting point of 153C, which is in the acceptable range indicating a pure substance. The systematic name for the product is 3-(4chlorophenyl)-1-(4-methoxyphenyl)prop-2-en-1-one. A total of four TLC plates were run, each comparing a mix of the products with the product via co-spot. Initially a 1:1 hexane, ethyl acetate developing solvent was used, but this yielded poor Rf values (co-spot Rf values of 0.956 and 0.089). Increasing concentrations of hexane were used until 1:9 ethyl acetate, hexane solution was deemed the best combination for different of the compounds (co-spot Rf values of 0.705, 0.432, and 0.045). The results indicate that the compounds were strongly nonpolar, with the reactants being more nonpolar than the product. Infrared spectroscopy was used to analyze functional groups and structures for the product. The product yielded a spectrum with three distinct peaks: 2840, 1655, and 1601. A short peak at 2840 indicates the presence of a methoxy group attached to a

benzene ring. One peak at 1655 indicates a C=O carbonyl group. Finally, a stretch at 1601 indicates a conjugated C=C bond characteristic of a benzene ring. Unfortunately, a chlorine group would appear in the fingerprint region, so its presence could not be verified with IR; however, all other data supports the structure of the chalcone product. Any percent yield above 50% is considered fair, while above 90% are considered excellent.4 A 91.0% yield for the crude product was excellent, while a 74.1% yield for the pure product was satisfactory. Conclusion The purpose of the experiment was to perform an aldol condensation reaction using a known aldehyde and ketone to form a chalcone product and analyzed. Reactants used were the aldehyde 4-chlorobenzaldehyde and the ketone 4-methoxyacetophenone to form 3-(4-chlorophenyl)-1-(4-methoxyphenyl)prop-2-en-1-one. Melting point of the experimental product matched the literature value, and analysis of the IR spectrum confirms the identity of the product.

Vogel, A.I., Tatchell, AR., Furnis, B.S., Hannaford, A.J. and P.W.G. Smith. Vogel's Textbook of Practical OrganicHall, 19936-3.