Experiment No. 1 Synthesis of Phenytoin PDF

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Synthesis of phenytoin...

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Experiment No: 1

SYNTHESIS OF PHENYTOIN FROM BENZIL----ANTI EPILEPIC DRUG

Aim: To synthesize phenytoin from benzil and urea. References: 1. Vogel’s Textbook of Organic Chemistry by Brian S. Furniss, Antony J. Hannaford, Peter W. G. Smith & Austin R. Tatchell; Fifth Edition; Page No. 1153. 2. Practical in Organic Chemistry, by Hitesh G. Raval, Sunil L. Baldania and Dimal A. Shah, Nirav Prakashan, Page No. 313. Requirements: Chemicals: Benzil, urea, sodium hydroxide, ethanol, concentrated hydrochloric acid. Apparatus: Round bottom flask 100 mL, reflux condenser, beaker 400 mL, graduated cylinders 50 mL or 100 mL, filtering flask with Buchner funnel, water bath, petri dish. Theory: Principle: Base catalyzed reaction between benzil and urea is used for synthesis of phenytoin. The reaction is proceeding via intramolecular cyclization to form an intermediate heterocylic pinacol, which on acidification yield hydantoin ( phenytoin) as a result of 1,2-diphenyl shift in pinacol rearrangement reaction. Reaction:

Mechanism:

Diphenyl hydantoin (phenytion) can be synthesized by treating the benzil with urea, in the presence of a strong base. The first step is a nucleophilic attack by a nitrogen atom of urea, following protonation of the intermediate, migration of a phenyl group occurs. The carbonyl carbon atom is not a carbo-cation, but it does have a partial positive charge due to the polarized C=O bond. Use: 1. Phenytoin is a widely used anticonvulsant drug. Phenytoin Sodium acts by reducing the spread of certain activities in the brain that result in seizures. 2. It is also used in the treatment of trigeminal neuralgia as well as certain cardiac arrhythmias. Procedure: Place 5.3 g (0.025 mol) of benzil, 3.0 g (0.005 mol) of urea, 15 mL of aqueous NaOH (30 %) and 75 mL of EtOH in a RBF of 100 mL capacity. Set up a reflux condenser with the RBF and boil using a water bath/electric heating mantle for at least 2 h. Cool to room temperature, pour the reaction mixture into 125 mL of water and mix carefully. Allow the reaction mixture to stand for 15 min and then filter the product under suction to remove an insoluble by-product. Render the filtrate strongly acidic with concentrated hydrochloric acid, cool in ice-water and immediately filter off the precipitated product under suction.

Recrystallise at least once from industrial spirit to obtain 2.8 g (44%) of pure 5,5diphenylhydantoin, m.pt. 297-298 0C. Preparation of hydantoin and thiohydantoin: In a round-bottomed flask equipped with a reflux condenser, a mixture of benzil (0.025 mol), urea or thiourea (0.05 mol), 15 mL of 30% aqueous sodium hydroxide solution and 75 mL of ethanol were placed. The mixture was heated under reflux for 2 hrs, after cooling to room temperature; the reaction mixture was poured into 125 mL of cold water and mixed thoroughly. The reaction mixture was allowed to stand for 15 min and it was filtered under suction. Then the filtrate was acidified with concentrated hydrochloric acid and the resulting precipitate was filtered and washed with water. The crude products were recrystallized from 95% ethanol Calculations: Molecular formula of benzil = C14H10O2 Molecular formula of phenytoin = C15H12N2O2 Molecular weight of benzil = 210 g/mole Molecular weight of phenytoin = 252 g/mole Theoretical yield 210 g benzil forms 252 g phenytoin Therefore, 5.3 g benzil will form………? (X) g phenytoin X = (252 X 5.3)/ 210 = 6.36 g Theoretical yield = 6.36 g Practical yield = …….. g % yield = (Practical yield /Theoretical yield)/ 100 Result: Phenytoin was synthesized and the percentage yield was found to be …….%....