1. syhtesis-of-phynetoin-students.pdf

Synthesis-of-phenytoin

1. Synthesis of Phenytoin
Dr. Pawan Kumar Gupta
Associate Professor
SVKM's Institute of Pharmacy, Dhule, Maharashtra
https://sites.google.com/view/pawanpharma79/about-me?authuser=1

2. Introduction
•Phynetoinis anti-
epileptic drug
•Hydantoin derivative
Phynetoin
(5,5-diphenylimidazolidine-2,4-dione)

3. Mechanism of Action
•Phenytoin bind voltage
dependant Sodium ion
channel
•It prolong the inactive
stage of sodium ion
channel
•It reduces the entry of
sodium ion inside the
neuronal membrane
•Inhibition of repetitive
generation of action
potential
•Prevention of discharge
of seizure
•
phenytoin

4. Synthesis of Phenytoin

6. Principle
•1. Formation of the benzilform benzaldehyde:
•Benzoincondensation:InpresenceoftheNaCN,twomoleculesofthe
benzaldehydearereactedandformedthebenzoin(2-hydroxy-1,2-diphenylethan-
1-one).InthepresenceoftheFeCl
3andacid,2-hydroxylgroupisgetoxidizedinto
carbonylgroupandformedbenzil(diphenylethane-1,2-dione)
•2. Formation of phenytoin from benzil:
•It is base catalysed reaction followed by pinacol-pinacolone rearrangement.
•In presence of the NaOH/EtOH and HCl (10%), reaction between benziland urea
are undergone intramolecular cyclization and formed pinacol intermediate (4,5-
dihydroxy-4,5-diphenylimidazolidin-2-one). This intermediate is containing two
hydroxyl groups in adjacent carbon (vicinal diol). In the acidic medium, this
intermediate is undergone for pinacol-pinacolone rearrangement (diphenyl shift)
and eventually get converted into the phenytoin.

7. •REQUIREMENTS
•Round bottom flask
•Measuring cylinder
•Beaker
•Pipette
•Funnel
•Reflux condensor
•Glass rod
•Filter paper
•Dropper

8. Chemicals required:
•Benzil
•Urea
•EtOH
•NaOH (30% w/v solution)
•HCl

9. Procedure
•1. Take 2 gm of the benziland transfer it into RBF (Round bottle flask).
•2. Take 1.2 gm urea and add into RBF
•3. Add 10 ml of ethanol into the RBF
•4. Mix well and 10ml of 30 % NaOH solution into RBF
•5. Attach the RBF to the reflux condenser and boil the content on water bath for 2 hrs.
•6. Transfer the reaction mixture into the beaker.
•7. Keep the beaker on the ice-bath and add 10ml of the cold water into the reaction mixture. Allow
the mixtures to keep it for sometime.
•8. In the reaction mixture, formation of the by-product is appeared.
•9. To remove the by product, filter the content with the help of funnel and filter paper.
•10. After the filtration, acidify the filtrate with 20% HCl drop-by-drop into the beaker (in order to
get around pH2). Precipitation of the is appeared in the beaker.
•11. Filter out the precipitate content with the help of the funnel and filter paper.
•12. This precipitated content are stick on the filter paper and it is crude phenytoin which can be
again recrystalized by using EtOH.
•13. Prepare TLC with Starting chemical (Benzil), final crude phenytoin and standard phenytoin. And
calculate Rf value of them.

10. Calculations
•Molecular weight the Benzil: 210.2
•Molecular formula of Benzil: C
14H
10O
2
•Molecular formula: C
15H
12N
2O
2
•Molecular weight the phytenoin: 252.26
•1 mol of the benzilis equivalent to 1 mol of the phenytoin

11. •Theoretical yield:
•210.23 gm benzilforms 252.26 gm phenytoin
•1 gm-------------------------------= 252.26/210.23
•X gm------------------------------= (252.26/210.2)*x
•Therefore, ___2 gm benzilwill form …….? (X) g
phenytoin
•X =(252.26 ×__2__)/210.23 = 2.399 gm
•Theoretical yield = 2.399 gm
•Practical yield = 2.16 gm

12. Calculations
(2.16/2.399)*100 = 90 % yield

13. •Use of Phenytoin:
•Anticonvulsants/antiepileticdrug: to control certain type
ofseizures, and to treat and preventseizuresthat may begin during
or aftersurgeryto thebrainor nervous system

14. Video links
•https://www.youtube.com/watch?v=bss7gmuWJRk
•https://www.youtube.com/watch?v=59jG3I7wRpQ
•https://www.youtube.com/watch?v=p5rXWRobVRg
•https://www.youtube.com/watch?v=sKs-sE28x14
•Synthesis of Benzil
•https://www.youtube.com/watch?v=upcNzdd5M7s