Synthesis of Phenytoin from Benzil and Urea

BACKGROUND

Aim: To prepare phenytoin from benzil and urea.

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.¹

Reaction:

Mechanism:

Use: 

It is a common antiepileptic drug.

REQUIREMENTS TO PREPARE PHENYTOIN

Chemicals:      

• Benzil
• Urea
• Sodium hydroxide
• Ethanol
• Concentrated hydrochloric acid

Apparatus:       

• Round-bottom flask – 100 ml
• Reflux condenser
• Crystallizing dish – 500 ml
• Heating mantle
• Stirrer
• Beaker – 400 ml
• Filtering flask with Büchner funnel
• Graduated cylinders – 100 ml and 50 ml
• Petri dish etc.

PROCEDURE

Place 5.3 g (0.025 mol) of benzil, 3.0 g (0.05 mol) of urea, 15 ml of aqueous sodium hydroxide solution (30%) and 75 ml of ethanol in a round bottomed flask of 100 ml capacity. Set up a reflux condenser with the flask and boil using an 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 about 2.8 g (44%) of pure 5,5-diphenylhydantoin, m.p. 297-298 °C.

Calculation:

Here limiting reagent is benzil; hence yield should be calculated from its amount taken.

C₁₄H₁₀O₂ =Molecular formula of benzil

C₁₅H₁₂N₂O₂ =Molecular formula of phenytoin

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 ×5.3)/210 = 6.36 g

Theoretical yield = 6.36 g

Practical yield = ————- g

% Yield = (Practical Yield)/(Theoretical Yield) × 100

CONCLUSION

Phenytoin was synthesized and the percentage yield was found to be………..%.

REFERENCES

1. Vogel’s Textbook of Practical 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.

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