International Journal of Medical Works

Kambohwell Publisher Enterprises

Vol. 1, Issue 2, PP. 5-8, Nov. 2015
www.kwpublisher.com

Synthesis And Characterization of Phenytoin Drug And Alpha

Benzilmonoxime From BEA711
Jamila khan, Arifullah khan, Tahirabashir

AbstractPhenytoin was prepared by the reaction of benzil

with urea in the presence of sodiumhydroxide. Alpha
benzilmonoxime was prepared by the reaction of benzil with
hydroxylamine hydrochloride in the presence of
sodiumhydroxide and ethanol. U.V techniques had been
utilized to observe the maximum absorption wavelength to
identify the chromophoric groups present in the molecule of
phenytoin and alpha benzilmonoxime. Melting point was taken
to determine the purity of these compounds. FT-IR had been
used for the determination of functional groups present in the
molecule of synthesized derivatives. Percentage yield was also
determined.
Keywords Benzil. Phenytoin, Alpha-Benzilmonoxime,
Hydroxylamine hydrochloride, Urea, Sodiumhydroxide

I.

INTRODUCTION

Benzil is a a-diketone and an organic compound. Diketone

have the two ketonic groups and have two alkyl groups which
may be same or different such as benzil which have the same
phenyl groups. Benzil is a yellow crystalline solid. Its m.p is
95C. It has the long C-C bond which is 1.5A. The PhCO
centers are planar. The benzoyl group pairs are twisted with
respect to each other and having the 11 rdihederal angle. The
molecular formula of benzil is (C6H5C0)2 [ I ].
Benzil is used to form the phenytoin which is medicme in
the treatment of epilepsy It is used as a photosensitive agent in
photo curable coatings, as a precursors for some
pharmaceutically important compound such as the antiepileptic
phenytoin and anticonvulsant dilantin, as a aluminum
electrolytic capacitors [2.3]. asa potent activator of microsomal
epoxide hydrolase in vitro, as a photosensitive agent. It is
unique because it produces a large number of reduction
products [4,5]. Benzilsare used as inhibitors of carboxyl
esterase enzymes, proteins involved in the metabolism of
esterified drugs and xenobiotics.
Phenytoin is the oldestnonsedativeantiseizure drug. It is
also known as muscle relaxant and anti-arrythmic. It is an
antiepileptic drug which is also called anticonvulsant. The
concentration of phenytoin must be maintained in the plasma
[6]. Phenytoin is composed of five membered hydantoin with
two phenyl groups at the five positions. Phenytoin has three
member molecule associated with urea and although has
Jamila wazir: Gomal university ,Dera Ismail Khan.
Email:jamilawazir.18@gmail.com.
Arif ullah khan: Shifa College of Nursing ,Islamabad. Pakistan.
Tahira bashir: government college university Faisalabad. Pakistan

pharmacological tool. It is an anticonvulsant and used to treat

various types of disorders such as epilepsy. Phenytoin is an
antiepileptic drug which decreases the action of epilepsy. It
plays the important role in controlling the action of brain and
nervous system during the treatment of epilepsy. It reduces the
flow of calcium and sodium ions and at high frequency the
flow of neurons is low which causes to prevent from the
electrical activity of seizure. Phenytoin reduces the release of
neurotransmitter and glutamate through them the body's central
nervous system is stimulated and increases the release of
GABA through it the body's central nervous system is
suppressant. The first action of Phenytoin is decrease the effect
of seizure on motor cortex. Epilepsy caused by the rapid flow
of sodium ions from neurons. It decreases the flow of sodium
ions by the release of GABA .Threshold is stabilized by
phenytoin against the extraordinary energetic excitability
occurred due to the environmental changes thus it reduces the
membrane potential gradient which causes the loss of posttetanic potentiation. Due to this losing cortex area has been
prevented from cortical seizure foci. Due to the effect of
chlonic seizure it reduces the action of brain stem centers. It
blocks the voltage sodium channel in neurons. By this action
neurological electrical recovery is delay from inactivation. The
inhibitory effect of phenytoin is depend on folic acid. The data
was published by Putnam Merrit in 1938 in which they use
phenytoin for the treatment of seizures. Thus phenytoin
appeared as an anticonvulsant agent at that time. More than
hundred diseases cured by phenytoin. They also found that it
has been used for the treatment of ulcers and many other
diseases due to its inhibitory effect on collagenase, facilitating
collagen deposition and also have a major effect on immune
system. It is distributed to muscles, into central nervous
system, fat and brain tissue where in endoplasmic reticulum it
cumulate [4]. a-Benzilmonoxime is a derivative of benzil. It is
known as chelating agent and having the special interest due to
their biological activities and semi-conducting properties. aBenzilmonoxime have the importance due to their
physiochemical properties and their reactivity patterns [12].

II.

RESEARCH ELABORATIONS

The
Benzil(97%),urea(95%)
and
ethanol(99.8%),
concentrated hydrochloric acid(98%) were obtained from
MERCK and used as received. Sodium-hydroxide (99%) was
obtained from Riedel-Dehaen, Glacial acetic acid(100%) from
Sigma-Alorich, Phenyl hydrazine(99%) was obtained from
china. Hydroxylamine hydrochloride(99%) British Drug
House(BDH).

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Spvthesisof phenytoin

test were performed for the identification of phenytoin which

was given in table 1.

EOUATION

TABLE NO:1
THE CHEMICAL TEST FOR PHENITOIN

Benzilphenytom
PROCEDURE
5.25g (0.025M) of benzil, Ig(0.025M) of Na0H in 100m1
of water,I.5g(0.025M) urea in 50m1 ethanol were taken in
250m1 of round bottom flask. The round bole flask was
equipped with a reflux condenser Mixture was heated under
reflux on a steam bath for 3-hours. This mixture was allowed to
cool at room temperature and poured the reaction mixture in
100m1 of cold water. The solution was filtered and acidified
the filtrate with concentrated hydrochloric acid. White
precipitates, m.p. 293 oC, formed filtered and washed with
water, recrystalized with ethanol.
SENTHESIS OF a- BENZILMONOXIME
EOUATION

Experiment

Observation

inference

Dissolve 20mg in
2m1 of ammonia and
add 5m1 of
silver nitrate

A white
precipitate is
produced

Phenytoin
is
Confirmed

Dissolve 5mg in Iml

Phenytoin
A blue violet
of boiling ethanol+2
is
colour is
droops
confirmed
produced
or copper (II)
sulphate and allow to
a-Benzilmonoxime
was synthesized by the reaction of benztl
cool.
with phenyl-hydrazinehyrochloride in the presence of ethanol
and sodium-hydroxide. Pure a-Benzilmonoxime was obtained
by the recrystallization of crude a-Benzilmonoxime with
ethanol. They were characterized by the FTIR. UV-VIS
spectroscopy and melting point. The melting point of this
comp0d was determined by the use of Gallenhamp melting
point apparatus. The physical properties of these were given in
table 2.
TABLE NO:2

PROCEDURE
21g (0.1M) of benzil was taken in beaker and little ethanol
was added to make a little thin paste. Concentrated aqueous
solution of 6.9g (0.1M) of hydroxylamine hydrochloride was
also added in this mixture and cooled the mixture in ice salt
bath at -5 C. Then 20% of 15g sodium hydroxide was added
drop-wise with rapid mechanical stirring. This procedure was
continued for 90 minutes. The temperature must be maintained
and was not risen above 0C. After 90 minutes it was diluted
with water. Filteration was done by sintered glass funnel to
remove the small quantity of unchanged benzil. Filtrate was
acidified with glacial acetic acid. It was allowed to stand for 30
minutes Filtered the a-benzilmonoxime and recrystalized from
ethanol. Yield was 82% and M P. 137C.Equations
III.

RESULTS

Phenytoin was synthesized by the reaction of benzil with

urea in the presence of sodium hydroxide. There were
impurities in phenytoin. Impurities were removed by washing
with water and then recrystallized the phenytoin with ethanol.
Then pure form of phenytoin was obtained. It was formed by
addition and condensation mechanism. After recrystalization
white crystals of phenytoin was obtained. Different chemical

International Journal of Medical Works

PHYSICAL PROPERTIES OF PHENYTOIN AND ALPHA

BENZILMONOXIME
Mol.for
Percentag
Color
Melti
mula
e
Name
and
ng
and
yield
Phase points
weight
C15H12N
71%
White
phenyton
2 O2
2930
solid
252.3
C14H11N Light
82%
AplhaBenzilmonoxi
1370
O2
pinkS
me
225.24
olid
The structure of all synthesized compounds was determined
by the FTIR. FTIR-Spectra of phenytoin showed that the broad
peak for C-N observed at 1342.95. This was the major group in
phenytoin. Peak came at 744,22 which indicated that CH bond
was present. The peak came at 1513 which indicated that C-C
bond was present. The peak which came at 1572.18 which
indicated that bond was present. These peaks showed that
aromatic ring was present which was phenyl group.The peaks
which came atl 342.95 indicated that C-N bond was present.
These peaks showed that amide group is present. Thus the
structure of phenytoin was confirmed by all these peaks which
came in FTIR-Spectra. The FTIR absorption of different
chemical bonds/functional groups of phenytoin were shown in
table no: 3.
TABLE NO :3

Vol. 1, Issue 2, PP. 4-8, Nov. 2015

FTIR ABSORPTION BANDS OF DIFFERENT

CHEMICAL BONDS/FUNCTIONAL GROUPS OF
PHENYTION
Range of
Observed
Functional Chemical
Type of
peaks
peaks
group
bond
vibration
(cm )
(cm )
Amide
Phenyl
Amide
Amide
Phenyl
Phenyl

C=O
C-H
N-H
C-N
C-C
C=C

Stretching
Stretching
Bending
Stretching
Stretching
Stretching

1692.06 16801700
730770
744.22
1598.07 15001650
1331.79 12801350
1513.03
1506
1527.18
1580

MR-SPECTRA OF ALPILI-BENZIL MONOXIME

The UV-VIS spectroscopy is also used for the identification
of compound which was given in table.
TABLE.5:
The max And Absorbance of Alpha-Benzilmonoxime
Name of Derivatives

FTIR spectra of a-benzilmonoxime showed that the broad

peak for C=N observed at 1620.04, for OH at 3200.07 which
indicated that oxime group was present. Different peaks of this
compound were observed such as CH peak at 730.07, C=C
peak at 1570.08 and C-C peak at 1511.07.A11 these
bands/peaks showed that phenyl group was present. The CO
peak came at 1685 which showed that ketonic group was
present.The FTIR absorption of different chemical
bonds/functional groups of phenytoin were shown in table no
4.
TABLE NO 4:
F77R absorption bands of different chemical bonds/
functional groups of alpha-benzilmonoxime
Observed Range of
Chemical
Type of
peaks
Functional
peaks
bond
vibration
(cm
)
group
(cm )
O-H

Stretching

3200.07

Ketone

CO

Stretching

1685.00

Oxime

C=N

Stretching

1620.04

Phenyl

C-H

Stretching

730.07

Phenyl

C-C

Stretching

1511.07

Phenyl

C=C

Stretching

1570.08

International Journal of Medical Works

Absorbance

Alpha305
2.374
Benzilmonoxime
The 2max And Absorbance OfAlaph-Benilrn,nv,xune.

FTIR SPECTRA OF PHENYTOIN

Oxime

max
(nm)

31503300
16751690
16201690
730-770

IV.

CONCLUSION

Phenytoin and Alpha-benzilmonxime have been prepared in

the laboratory. They are playing important role in industry,
biomedical fields, extraction and analytical chemistry.
Phenytoin is the famous derivative of benzil which is widely
used for the treatment of different diseases_ Structure
determination of benzil derivatives were obtained by the use
of FTIR and UV-VIS spectroscopy. FTIR spectra of
Phenytoin showed the peak for C-N at 1342.95 cm's and for
CO at 1692.06 cm'', FTIR spectra of a-Benzilmonoxime
showed the peak for OH at 3200.07 cnil and for CO at 1685
em's. UV technique was also applied on determining the
maximum absorbance Alpha-benzilmonoxime which was
2.374. Thus the structures of benzil derivatives were
determined.
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Vol. 1, Issue 2, PP. 4-8, Nov. 2015

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Vol. 1, Issue 2, PP. 4-8, Nov. 2015