Thiantoin, Lilly, US,1950
The 5-phenyl-5-(2-thienyl)hydantoin is prepared by heating a mixture of 5.64 g (0.03 mol) of phenyl-(2-thienyl)ketone, 3.25 g (0.03 mol) of potassium cyanide and 10.2 g (0.09 mol) of ammonium carbonate in 75 cc of 50% ethanol for 28 hours at a temperature of about 110°C. An additional 3.25 g of potassium cyanide and 3 g of ammonium carbonate are added and the mixture heated for 24 hours at about 110°C.
The reaction mixture is removed and about half of the liquid evaporated, an oil separating during the process. The mixture is acidified with concentrated hydrochloric acid and extracted with two 100 cc portions of ether. The extracts, which contain the 5-phenyl-5-(2-thienyl)hydantoin, are combined and the combined ether extracts are shaken with two 25 cc portions of 5% potassium hydroxide solution. The alkaline solution, which dissolves the 5phenyl-5-(2-thienyl)hydantoin to form the potassium salt thereof, is acidifed with hydrochloric acid and heated to expel ether.
By the process of purification, 4.3 g of 5-phenyl-5-(2-thienyl)hydantoin is obtained, and from the ether layer, 2.2 g of unreacted ketone. The yield of the 5-phenyl-5-(2-thienyl)hydantoin is about 56%. The melting point of the purified 5-phenyl-5-(2-thienyl)hydantoinis about 256°C to 257°C.
