Toluene → 4-methyl-3-oxo-N-phenylpentanamide

Participants

Reaction Conditions

Reaction Steps

A three-necked, 12 L round bottom flask equipped with a mechanical stirrer, a thermometer, and set up for distillation was charged with 2.6 L of toluene, 1.73 kg (12 mol) of methyl 4-methyl-3-oxopentanoate and 72 g (1.18 mol) of ethylenediamine. The mixture was heated to 80° C. and charged with 0.49 kg of aniline. The mixture was brought to reflux and distillation was started. After 40 minutes, a further 0.245 kg of aniline was charged and, at 40 minute intervals, a further two portions of aniline (0.245 and 0.25 kg) were charged. Distillation was continued for a further 1 to 5 hours until a total of 985 mL of solvent was removed. The solution was stirred at room temperature for 16 hours, and a further 550 mL of solvent was removed by vacuum distillation (at approximately 85 mm Hg). The mixture was cooled, and 2 L of water was charged to provide an oil. The mixture was warmed to 40° C., and a further 1.0 L of water was charged. Seven hundred milliliters of toluene/water mixture was removed by vacuum distillation (approximately 20 mm Hg). Two liters of water were charged, and the mixture allowed to stand for 10 days. The product was isolated by filtration and washed with three portions of hexane. Drying in vacuo gave 1.7 kg of 4-methyl-3-oxo-N-phenylpentanamide as a hydrate; mp 46.5-58.8° C.

Provenance & Evidence