Ethanol → Valproic Acid

Participants

Reaction Conditions

Reaction Steps

A mixture of 70 g of p-toluenesulfonic acid monohydrate, 140 g of diethyl dipropylmalonate and 9 ml of water was heated to reflux in a flask equipped with a distillation column packed with Raschig rings. Ethanol was distilled as it formed and the pot temperature was maintained at 120°-155° C. by periodic addition of water to the pot. After 5 hours, 25 ml of water had been added and the evolution of ethanol had nearly stopped. The mixture was maintained at 140° C. for 18 hours and then was cooled and treated with 100 ml of water. The layers were separated to afford 72.2 g (87.8% yield) of valproic acid as a light brown liquid. The water layer was washed with 50 ml of toluene and the toluene was combined with the crude valproic acid layer. Vacuum distillation afforded a colorless valproic acid fraction (72 g, 87% yield) boiling at 132° C./28" Hg.

Provenance & Evidence