Acetophenetidin

Data Tables:

Williamson Ether Synthesis

Reagents MW (g/mol) Amount Mol Lit. Mp

p-Acetimido phenol 151.17 1.513 g 0.010 N/A

Bromoethane 108.97 1.1 mL 0.0147 N/A

Products MW (g/mol) Amount (g) Mol Lit. Mp Observed Mp Percent

Yield Percent Recovery

Crude product 179.22 0.498 0.0028 133-136Ð'Ñ"C 132-134Ð'Ñ"C 73.82% N/A

Recryst. Product 179.22 0.416 0.0023 133-136Ð'Ñ"C 143-145Ð'Ñ"C N/A 83.53%

Amide Synthesis

Reagents MW (g/mol) Amount Mol Lit. Mp

p-phenetidine 137.18 2..0 g 0.0146 N/A

Acetic anhydride 102.09 1.8 mL 0.0190 N/A

Products MW (g/mol) Amount (g) Mol Lit. Mp Observed Mp Percent

Yield Percent Recovery

Crude product 179.22 0.5 0.0028 133-136Ð'Ñ"C 131.9-133.3Ð'Ñ"C 200.15% N/A

Recryst. Product 179.22 0.336 0.0019 133-136Ð'Ñ"C 144.5-146Ð'Ñ"C N/A 67.2%

Introduction:

Acetophenetidin was synthesized utilizing the Williamson ether synthesis. The product from this synthesis was compared to a product synthesized using another method, the amide synthesis method, in order to ascertain which method was most efficient for the synthesis of acetophenetidin. For the Williamson ether synthesis, the reagents sodium methoxide, ethanol, and p-acetomidophenol were added to a 25mL flask. Then bromoethane was added and the reaction was refluxed using a water-cooled condenser. The product was allowed to crystallize in an ice bath and collected using vacuum filtration. The product was also recrystallized and compared to the recrystallized product of the second method. Melting points of both crude and recrystallized products were obtained, and percent yield and percent recovery were calculated.

Results and Discussion:

The first step in the Williamson ether synthesis of acetephenetidin was to combine sodium methoxide, ethanol, and p-acetomidophenol in a 25mL flask. This resulted in the deprotonation of p-acetomidophenol, the first step of the synthesis. After this bromoethane was added to the reaction mixture which resulted in further reaction, evident through the visible change in color of the solution from colorless to pink. Addition of bromoethane to the reaction mixture resulted in a substitution reaction, which after reflux using a water-cooled condenser, yielded the end product acetophenetidin. The product was pale pink in color and was allowed to crystallize in an ice bath, which produced powdery pale pink flakes, which were collected through vacuum filtration. The synthesis resulted in a 73.82% yield, and the product had a melting point of 132-134Ð'oC. This is not a very high yield and this could be due to insufficient cooling time between the end of reflux and the ice bath, or insufficient time in the ice bath. The melting point is close to the literature Mp, and also has a narrow range which is indicative of minimal impurities. The product was also recrystallized using a minimum amount of boiling water as the recrystallization solvent, since the product was soluble in boiling water but insoluble in room temperature water. This gave an 83.53% recovery yield and a melting point of 144-146Ð'oC, which is a bit high and indicates the presence of impurities. .

Post Lab Questions:

1. The amide synthesis gave a crude product yield of 200.15%. This was due to the fact that acid may have been left in the product and was never sufficiently washed out. The melting point for the product of this synthesis was 131.9-133.3Ð'oC. The Williamson Ether Synthesis gave a crude product yield of 73.82%, and the product had a melting point of 132-134Ð'oC.