Synthesis Of 4-Hydroxy-1 Lab Report

Abstract – The synthesis of 4-hydroxy-4,4-diphenylbutn-2-one was a three week multi-step project. The steps involved protecting the ketone of ethyl acetoacetate with a ketal group, followed by preparation and reaction with Grignard, then purification by extraction and recrystallization. The yield was 78.5%, but there are impurities present suggested by 1H-NMR, IR, and TLC. However, the results do indicate the desired hydroxyketone was formed.

Introduction: The purpose of this multi-step lab was to synthesize 4-hydroxy-4,4-diphenylbutan-2-one from ethyl acetoacetate. The Grignard reaction is widely used to react with ketones and aldehydes to give alcohols, however, it cannot selectively retained carbonyl groups already present in a structure.1,2
The final product from Week 3 was an orange liquid with a yield of 78.5% (Table 1). Melting points of liquids could not be obtained. Refer to Figure 1 for TLC plate of the crude final product and Table 1 for the IR, MS, and 1H-NMR data. The mechanism for ketal formation is in Scheme 1, while the Grignard preparation and reaction is in Scheme 2. Scheme 3 has the general reaction scheme for the synthesis.

Discussion:
The physical properties of the Week 1 product corresponded to the expected found in the literature – a clear liquid.4 However, based on Sigma-Aldrich the Week 3 product was supposed to be a solid, however it was an orange liquid.4 The yield for the Week 1 intermediate was 3 g, which is approximately half of the theoretical, however, the weight is representative of how much product is present because the IR shows the product is dry due to the lack of an O-H stretch (Figure 2). On the other hand, the yield for the
Based on common solvent impurities the peak at ~3.33 ppm is water, ~2.30, 7.18, and 7.25 ppm is toluene, ~1.09 ppm is diethyl ether, ~3.41 is ethylene glycol, and ~2.50 ppm is DMSO.6 The 1H NMR of the intermediate shows a shielded proton peak in the 0.9-1.7 ppm region with an integration of 3 protons as expected of the methyl group furthest away from the electron withdrawing oxygens (Figure 4). The second most shielded peak also has an integration of 3, and would be the methyl group attached to the ketal group. The subsequent C and E peaks have the correct integration and splitting pattern for their appropriate locations as depicted in Figure 4. The protons on D show a singlet as the protons on both carbons are similar due to the symmetry of the ketal group, thus they would be considered equivalent and would not split each other. The possible impurities are caused by leftover starting reagent. The 1H NMR of the final product shows protons present on the aromatic rings seen as peaks at 6.5-8.5 ppm, due to the symmetry of the protons D, E, and F have similar electron environments despite being on separate rings (Figure 5). These benzyl protons have the appropriate integration values, and is a good indicator that two equivalences of phenyl magnesium bromide added. The peak at ~5.44 ppm shows an O-H