Preparation of Phenobarbital-D5_Kain Industrial Additive

Background and overview^[1]

Phenobarbital is a long-acting hypnotic drug with sedative, hypnotic, anticonvulsant and anti-epileptic effects. In addition, this drug is a hepatic microsomal enzyme inducer, which can induce hepatic microsomal glucuronosyltransferase, promote the combination of bilirubin and glucuronic acid, reduce the concentration of bilirubin in the plasma, and can treat neonatal nuclear jaundice. . Used for: ① Sedation: such as anxiety, irritability, hyperthyroidism, and hypertension. ②Hypnosis: Occasionally used for intractable insomnia. People are often tired and sleepy after sleep. ③Anticonvulsants: against convulsions caused by central nervous system stimulants or diseases such as high fever, tetanus, encephalitis, etc. ④ Use in combination with antipyretic and analgesic drugs to enhance its analgesic effect. ⑤Administer before anesthesia. ⑥Grand mal epilepsy: The effect occurs quickly and can also be combined with phenytoin. Phenobarbital-D5 is a deuterated derivative of phenobarbital, which can improve its physical and chemical properties.

Preparation^[2]

Phenobarbital-D5 is prepared as follows: under nitrogen, add 1.0g (0.0166 mole) urea and 1.0g (0.0416 mole) to a 50ml round bottom flask equipped with a stirring rod, reflux condenser and rubber septum. Sodium hydride. While stirring, 3.4 g (0.0126 mol) of ethyl-D5-phenylmalonate diethyl ester in 40 ml of absolute ethanol was slowly added via cannula. The mixture was refluxed for 24 hours and then added to 50 ml of 0.1 NH2SO and 25 ml of crushed ice. After extraction with diethyl ether, drying and evaporation of the solvent to a small volume, phenobarbital-D5 was obtained by column chromatography (silica gel; E.M. reagent, 0.5-0.2 mm mesh, 2.5x28 cm), and 200 ml of anhydrous diethyl ether was added. Evaporation of the ether yielded 2.0 g (65%) of pure Phenobarbital-D5.