1. SYNTHESIS OF POSSIBLESYNTHESIS OF POSSIBLE
ANTICONVULSANT DRUGSANTICONVULSANT DRUGS
by
SROTA DAWN
B.PHARM,4TH
YEAR
REG. NO:
ROLL NO:
OF
BENGAL SCHOOL OF TECHNOLOOGY
Under the supervision
Of
PROF.(DR) DHANANJAY PAL
Project submitted for the partial fulfillment of
the degree of B.PHARM
Under
West Bengal University of Technology

2. SYNTHESIS OFSYNTHESIS OF
POSSIBLEPOSSIBLE
ANTICONVULSANTANTICONVULSANT
DRUGSDRUGS

3. Under the GUIDANCE OF……Under the GUIDANCE OF……
Dr. Dhananjay PalDr. Dhananjay Pal
M.Pharm,Ph.D. HOD ofM.Pharm,Ph.D. HOD of
Pharmaceutical chemistryPharmaceutical chemistry
Bengal School Of Technology
Sugandha,Delhi road
Hooghly-712102

4. CERTIFICATECERTIFICATE
THIS IS TO CERTIFY THAT MISS. SROTA DAWN,ATHIS IS TO CERTIFY THAT MISS. SROTA DAWN,A
CANDIDATE OF B.PHARM,7CANDIDATE OF B.PHARM,7THTH
SEM OF BENGAL SCHOOLSEM OF BENGAL SCHOOL
OF TECHNOLOGY HAS CARRIED OUT HER PROJECTOF TECHNOLOGY HAS CARRIED OUT HER PROJECT
WORK ENTITLEDWORK ENTITLED
““SYNTHESIS OF POSSIBLE ANTICONVULSANT”SYNTHESIS OF POSSIBLE ANTICONVULSANT”
IS A RECORD OF INDEPENDENT WORK UNDER MYIS A RECORD OF INDEPENDENT WORK UNDER MY
SUPERVISION.SUPERVISION.
PROF. (DR.) DHANANJAY PALPROF. (DR.) DHANANJAY PAL
BENGAL SCHOOL OF TECHNOLOGYBENGAL SCHOOL OF TECHNOLOGY
DR.GOUTAM CHATTERJEE,DR.GOUTAM CHATTERJEE,
PRINCIPALPRINCIPAL
BENGAL SCHOOL OF TECHNOLOGYBENGAL SCHOOL OF TECHNOLOGY
SUGANDHA,DEHLI ROAD,HOOGHLY-712102SUGANDHA,DEHLI ROAD,HOOGHLY-712102

5. EPILEPSIES (Definition) :
These are groups of CENTRAL NERVOUS SYSTEM
disorders
characterised by PAROXYSMAL CEREBRAL DYSRHYTHMIA ,
manifestation of brief episodes of seizures ,loss and disturbance of
consciousness ,with
or with or without characteristic body movements(convulsions) ,
Sensory or psychiatric phenomena.
INTRODUCTION
India is one of the dense populated country, people are attacked
by various kinds of diseases as time goes on . Epilepsy is
One of them which is a risk factor for patient in case of any
situation.
About 40 million people world-wide suffer from epilepsy.
In 70% of patients who have epilepsy, no specific cause can be
determined. Epilepsy can be acquired as a result of neurological
injury and can also occur as a part of
Systemic medical illness

6. Nature of epilepsy
Epilepsy affects about 0.5% of the population.
The characteristic event is the seizure, which may be
associated with convulsions but often takes other forms.
The seizure is caused by an asynchronous high-
frequency discharge of a group of neurons, starting
locally and spreading to a varying extent to affect other
parts of the brain. In absence seizures, the discharge is
regular and oscillatory.
Partial seizures affect localised brain regions, and the
attack may involve mainly motor, sensory or
behavioural phenomena. Unconsciousness occurs when
the reticular formation is involved. Generalised seizures
affect the whole brain.

7. •Two common forms of epilepsy are the tonic-clonic fit
(grand mal) and the absence seizure (petit mal). Status
epilepticus is a life-threatening condition in which seizure
activity is uninterrupted.
•Many animal models have been devised, including
electrically and chemically induced generalised seizures,
production of local chemical damage, and kindling. These
provide good prediction of antiepileptic drug effects in
humans.
•The neurochemical basis of the abnormal discharge is not
well understood. It may be associated with enhanced
excitatory amino acid transmission, impaired inhibitory
transmission, or abnormal electrical properties of the
affected cells. Several susceptibility genes, mainly encoding
neuronal ion channels, have been identified.
•Repeated epileptic discharge can cause neuronal death
(excitotoxicity).
•Current drug therapy is effective in 70-80% of patients

8. Anticonvulsant agentsAnticonvulsant agents
Anticonvulsant agents are those which are use to treat,
control or to eliminate convulsions.
Anticonvulsants are the drug which selectively depresses
Central Nervous System(C N S).
Types of epilepsyTypes of epilepsy
There are four types of epilepsy
1.Grandmal epilepsy
2. Petitmal epilepsy
3.Jacksionian epilepsy
4.Psycomotor epilepsy

9. 1.1. GrandmalGrandmal epilepsyepilepsy ::
In which seizures lasts for 2 to 5 minutes. It isIn which seizures lasts for 2 to 5 minutes. It is
characterized by sudden loss of consiousness.Thecharacterized by sudden loss of consiousness.The
patientspatients
has tonic as well as clonic convulsions of all muscles andhas tonic as well as clonic convulsions of all muscles and
there is urinary incontinence.there is urinary incontinence.
In this type of epilepsy the person experiencesIn this type of epilepsy the person experiences
anan auraaura (this consists of certain sounds , fear and(this consists of certain sounds , fear and
discomfortdiscomfort
immediately before a seizure)immediately before a seizure)
2.2.PetitmalPetitmal epilepsyepilepsy ::
The seizures lasts for 5 to 30 seconds beingThe seizures lasts for 5 to 30 seconds being
characterized by brief attacks of unconsciousness. Thischaracterized by brief attacks of unconsciousness. This
type of epilepsy is most frequently found in children attype of epilepsy is most frequently found in children at
age of 4 to 8 years.age of 4 to 8 years.

10. 3.3.Jacksonian epilepsyJacksonian epilepsy ::
It is usually associated with lesion of a certain partIt is usually associated with lesion of a certain part
of the brain(cerebral cortex).Jacksionian epilepsy is characterizedof the brain(cerebral cortex).Jacksionian epilepsy is characterized
by local clonic type convulsions (thumb, big toe etc.)The seizureby local clonic type convulsions (thumb, big toe etc.)The seizure
normally lasts fromnormally lasts from
1 to 2 minutes.1 to 2 minutes.
44..Psychomotor epilepsyPsychomotor epilepsy ::
It is characterized by attacks without convulsionsIt is characterized by attacks without convulsions
lasting from 2 to 3 minutes. The individual may experience an auralasting from 2 to 3 minutes. The individual may experience an aura
(such as hallucinations or a sense of fear).(such as hallucinations or a sense of fear).

11. Mechanism of action of antiepileptic drugs
•Current antiepileptic drugs are thought to act mainly by
three main mechanisms:
• reducing electrical excitability of cell membranes,
mainly through use-dependent block of sodium
channels
• enhancing GABA-mediated synaptic inhibition; this
may be achieved by an enhanced postsynaptic action of
GABA, by inhibiting GABA transaminase, or by drugs
with direct GABA agonist properties
• inhibiting T-type calcium channels (important in
controlling absence seizures).
•Newer drugs act by other mechanisms yet to be elucidated.
•Drugs that block glutamate receptors are effective in animal
models but are unsuitable for clinical use.

12. 1.BARBITURATES Phenobarbitone
2.DEOXYBARBITURATES Primidone
3.HYDANTOINS Phenytoin,Phosphenytoin
4.IMINOSTILBENES Carbamazepine,Oxcarbamazepine
5.SUCCINIMIDES Ethosuximide
6.ALIPHATIC CARBOXYLIC ACIDS Valproic acid(sodium
valproate),Divalproex
7.BENZODIAZEPINES Clonazepam,Diazepam,Lorazepam,Cloba
zepam
8.PHENYLTRIAZINE Lamotrigine
9.CYCLIC GABA ANALOGUE Gabapentin
10.NEWER DRUGS Vigabatrin,Topiramate,Tiagabine,Z
onisamide,Levetiracetam

13. Structure of some importantStructure of some important AnticonvulsantsAnticonvulsants
N
N
O
O
R
R 2
1
R
H
Generral structure of
HYDANTOIN
derivatives
ON
N
O
O
H
R
R
R1
2
General structure of BARBTTURATES
N O
O
O
CH
R R 1
3
General structure of
Oxazolidinediones
N
O
O
R
R 2
1
R
Generral structure of
Succinimides

14. From the above structures we can conclude that,
Most anticonvulsants drugs like
HYDANTOIN (eg.PHENYTOIN);
BARBITURATES(eg.PHENOBARBITAL);
OXAZOLIDINEDIONES;SUCCNIMIDES contains the following group:
We assume that THIS GROUP MAY ACTS AS A
PHARMACOPHORE FOR
ANTICONVULSANT DRUGS

15. PROJECT SCHEME

17. PRESENT PROJECT WORK

18. Synthesis of Butyl derivative of Phthalimide
Step 1: preparation of Phthalic Anhydride
Theory:
In the first step we have to prepare Phthalic anhydride from
Phthalic acid in the presence of acetic anhydride. Acetic
anhydride take
One molecule of water from Phthalic acid and formation of
phthalic anhydride takes place.
Physical characteristics of
Phthalic acid
Physical characteristics of
phthalic anhydride
Molecular wt=(96+6+64)=
166
Molecular wt=(48+6+48)=
102
Melting point=230◦c Melting point=130◦c

19. Reaction:
Physical characteristics of
Phthalic acid
Physical characteristics of
phthalic anhydride
Solubility:
Dissolve ,
1gm in 160ml. Water;
10ml. Alcohol;
250ml.ether;
5.3ml. methanol
Solubility:
Dissolve,
1gm in 162 parts water;
125 parts cs2;
soluble in alcohol;
sparingly soluble in ether.

20. PROCEDURE:
1.Phthalic acid and acetic anhydride are taken in a round
bottom flask in 1:2 mole ratio.
2.They are heated and refluxed for 2 hours in a water
bath.
3. A mass white colored crystalline product is prepared.
4.Obtained product is filtered and then the mass was
taken and dried.
5.Measure the melting point of the obtained product .
OBSERVATION:
Melting point of the obtained product is 129◦c,which is
near to the melting point of phthalic anhydride 130◦c.
(according to Mark Index)
CONCLUSION:
The obtained product is phthalic anhydride.

21. Synthesis of Butyl derivative of Phthalimide
Step 2: preparation of Butyl Phthalimide
Theory:
In the second step we have to prepare Butyl
phthalimide from Phthalic anhydride in the presence of Butyl
amine. Physical characteristics of butyl amine are as follows,
Butyl amine:
Molecular wt : 73.14
Density : 0.736gm/cc
Phthalimide
It is slightly soluble in water,100gm. Of boiling alcohol
dissolves 5gm. Of phthalimide.Almost insoluble in benzene and
Pet ether . Fairly soluble in boiling acetic acid. Freely soluble in
aq.alkali hydroxide.

22. Reaction:

23. PROCEDURE:
1. Phthalic anhydride and butyl amine are taken in a
round bottom flask in 1:2 mole ratio.
Phthalic anhydride taken 5gm,butyl amine taken 6.8 ml.
2. They are heated and refluxed for 2 hours in an oil
bath.
Temperature of the oil bath is maintained in between
140◦c-160◦c
3. A mass white colored crystalline product is
prepared.
4.Obtained product is filtered and then the mass was
taken and dried.
5.Measure the melting point of the obtained product .
 RECRYSTALLISATION PROCEDURE:
The crude product is recrystallized to remove the
impurities or to remove the other unwanted compounds
which are formed during the reaction procedure.

24. 1 . The obtained crude product is 1st
taken in a beaker .
2 . Then the product is dissolved in solution of alcohol and
water (1:1) .
3 . Heat the drug solution till the drug completely dissolves
in the media.
4 . Cool the solution of drug, during cooling recrystallized
product is obtained.
5 . Determine the melting point of the filtered material .
6 . This process is repeated until a stable melting point is
observed.
PROCEDURE:

25. OBSERVATION:
Melting point of the obtained crude product 95◦c,
AFTER RECRYSTALLIZATION:
After 1ST
recrystallization : 97◦c-98◦c
After 2nd
recrystallization :100◦c
After 3rd
recrystallization :102◦c-103◦c
After 4th
recrystallization :106◦c-108◦c
After 5th
recrystallization :106◦c-108◦c
Solubility
The drug is freely soluble in
boiling water , warm ethyl alcohol,
insoluble in water , benzene.
Colour:
Off white.
REPORT:
The obtained product is phthalic anhydride

26. Discussion and conclusion
Our project “preparation of possible anticonvulsant” was
very challenging project for us . we have prepare
The butyl derivative of phthalimide. After proper
characterization through proper techniques , our
next target is to evaluate the biological activity
Of the compound for anticonvulsant activity.

27. References
1.Willams David A. ,Lekme thomas l.,
Foyes Principle of Medicinal
Chemistry 5th
ed.(2006)
2.Tripathi K.D. ,Essentials of Medical
Pharmacology,6th
ed.(2008)
3.Seth S.D., Textbook of
Pharmacology,2th
ed.(1999)
4.The Mark Index,13th
ed.(2001)
5.Vogel H. Gerhard , Drug Discovery
and Evaluation,2nd
ed.

28. MECHANISMMECHANISM ofof ACTIONACTION ofof ANTICONVULSANTSANTICONVULSANTS
Seizures are caused by abnormal stimulations ofSeizures are caused by abnormal stimulations of
nerves in brain.nerves in brain.
Generally anticonvulsants reduce the excitabilityGenerally anticonvulsants reduce the excitability
of neurons (eg.nerve cells) of the brain . Whenof neurons (eg.nerve cells) of the brain . When
neurons excitability decreased ,seizures areneurons excitability decreased ,seizures are
reduced in intensity and frequency of occurrencereduced in intensity and frequency of occurrence
is virtually eliminated .It is believed thatis virtually eliminated .It is believed that
anticonvulsants suppress seizure byanticonvulsants suppress seizure by
Depressing the cerebral cortex of the brain ,Depressing the cerebral cortex of the brain ,
thereby raising thethereby raising the
C N S to convulsive stimuli .C N S to convulsive stimuli .