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GSJ: Volume 8, Issue 11, November 2020, Online: ISSN 2320-9186
www.globalscientificjournal.com
Synthesis and characterization of new derivatives of 4-fluoro
benzoic acid as bioactive compound
Samreen Gul khan1, Amna Tarteel1*, Muhammad Farman2*, Ali Usman1, Maryam Azam1, Muhammad
irfan1, Umer Hayat1, Awais Munir3, Muhammad Usman Rasheed1
1Department of Chemistry, Government College University, Faisalabad, Pakistan.
2Department of Chemistry, University of Engineering and Technology, Lahore, Pakistan.
3Department of Environmental Sciences, Islamia University of Bahawalpur, Pakistan.
Email address:
farman.gujjjar@gmail.com
Abstract:
Infectious microbial diseases are a serious issue of the whole World. Medicinal chemists & biologists are
paying special attention on disease causing pathogens and bacteria because risk of diseases is increasing day by day
& fatal for life. A series of hydrazide hydrazones of 4-fluorobenzoic acid hydrazide were prepared and evaluated as
potential antimicrobial agents. Reaction progress was checked by using pre-coated silica gel aluminium packed thin
layer plates with the help of ethyl acetate & n-hexane that will serve as mobile phase. These new compounds were
characterized by their physical properties (melting point, Colour, TLC spot, Molecular formula, Molecular wt,
%yield, solubility), the structures were confirmed by elemental analysis, IR spectral methods.
Keywords: 4-fluoro benzoic acid, IR, Antimicrobial activity
1. INTRODUCTION
In present days, infectious microbial diseases are a
serious issue of the whole World. Medicinal chemists
& biologists are paying special attention on disease
causing pathogens and bacteria because risk of
diseases is increasing day by day & fatal for life.
Literature survey reveals that resistance has been
increased for existing antimicrobial drugs. So, it is
necessary to design novel biologically important
antimicrobial drugs with good activity profiles. These
facts have made the synthesis and characterization of
new drugs an ongoing process for research purposes.
Two methodologies are in use for this purpose one is
the use of already existing materials and second one
is the use of new self created procedure. Hetero-
cycles specially oxadiazoles are of great importance
for this task and are in use for synthesizing new drugs
from last decades. Organic compounds are
characterized such that some or all the atoms are
linked through ring structure with at least one non-
carbon atom. In heterocyclic compounds the cyclic
part represents the presence of at least one ring
structure and the term hetero represents the one
atom other than carbon in the ring. On the basis of
general structure heterocyclic compounds resemble
to the organic compounds but due to the hetero-
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atoms they show unique physical and chemical
properties (Kunied & Mustsanga, 2012).
History of hetero cyclic compounds was started with
the development of organic chemistry in 1800s. In
1832, Dobereiner designed a reaction between starch
and sulfuric acid to produce a furan named furfural.
By using dry distillation of bones, Runge synthesized
pyrrole in1834. Treibs in 1936, separated derivatives
of chlorophyll from crude oil and also explained
biological origin of petroleum (Arora et al., 2012).
Heterocyclic chemistry constitutes almost 65% of
organic chemistry. It has wide range of applications. It
has a vital role in carrying out enzymatic reactions
necessary for life.
Large number of hetero-cyclic compounds are in
clinical use & are pharmacologically very active.
Heterocyclic bases like pyrimidines and purines make
the genetic material DNA. Effect of induction due to
hetero-atom makes oxadiazole a weak base.
• As density of electrons is low for carbons so
oxadiazole ring shows high resistance towards
electrophilic substitution reactions.
• Attack of electrophile substitution may happens
on nitrogen if a change takes place in electron
releasing groups.
• In oxadiazole ring nucleophilic substitution is
difficult but if substituting agent is halogen atom
then nucleophile is substituted in the ring by
releasing the halogen atom.
• The ring cleavage reactions in oxadiazoles are
also of great importance because of applications
in pharmacological industry. As a result of these
reactions compounds having ring structures and
nitrogen are obtained.
For medicinal chemists, it is a challenging task to
prepare novel drugs. Oxadiazoles have shown a large
number of applications like anti-bacterial, anti-
inflamatory, analgesic, anti-tumor, anti-convulsant,
anti-oxidant herbicidal and anti-fungal activities.Two
basic approaches are adapted by chemists for
developing novel drugs:
• Forming analogues as well as their derivative
formation gives new substituted compounds for
good and developed treatment.
• Searching & preparing new compounds that
bacteria and diseases has never been presented
before.
For this purpose oxadiazoles and their derivatives are
considered as important antiinflammatory,
anti-convulsant and anti-bacterial agents.
1-Rivera et al. (2006), developed a pathway of
forming 2-amino-5-phenyl-1,3,4-oxadiazole by
performing oxidative cyclization of different oxidizing
agents like Nbromosuccinamide, H2O2 & bleach etc.
NaOH was used as base & a catalyst naming
potassium iodide.
2-Kiselyov et al. (2010) synthesized oxadiazoles by
performing condensation of C3H3NS derivative
through hydrazine hydrate for about 4.2 hours. Further
reaction of transitional molecule was carried out and
desired compound was synthesized.
3-Kamble et al., (2008) used microwave for the
synthesis of oxadiazoles. The microwave method is a
cleaner technique which gives higher production in
lesser time.
Within the sight chalcones exhibit swift hydrazine
hydrate cyclization. Medium used was with formic
acid and polyethylene glycol. Titled product was
converted into derivatives of oxadiazole by reacting it
with acetic acid.
4-Cyclization of acyl thiosemicarbazide was used to
synthesize 5-aryl-2-amino-1,3,4- oxadiazoles. 1,3-
dibromo-5,5-dimethylhydantoin was used as oxidizing
agent. The important benefit of this method is that it is
safe to use, easily available and cheap (Rivera et al.,
2006).
Thiophene is the most common sulfur based hetero-
cycle. In physical and chemical properties it resembles
benzene a lot. During the purification of benzene it
was obtained for the first time. Thiophene is a
common contaminant of benzene and is obtained from
natural
resources. It was discovered in the late 19th century.
In the furan ring, when the two methane (-CH=)
groups are interchanged with two pyridine type
nitrogen, oxadiazole or furadiazole is obtained with
molecular representation C2H2N2O (de Oliveira et
al., 2012). This replacement decreases the aromaticity
of the ring
such that it starts reflecting the characteristics of
conjugate diene (Bachwani & Sharma,2011). There
exist four isomers of oxadiazole having nitrogen at
different positions and isomerization is also due to this
reason. Isomers are 1,2,5-oxadiazole, 1,2,5-
oxadiazole,1,2,4-oxadiazole and 1,2,4-oxadiazole
(Somani et al., 2011).
But 1,2,3-oxadiazole is not stable and opens readily
giving diazoketone tautomer (Leite et al., 2000),
(Schmidt et al., 2003), (Salahuddin et al., 2017).
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Biological activities of some compounds
Compounds
Biological activity
Reference
2-arylaminosulfonylmethyl-5- aryl-
1,3,4-oxadiazole
Anti-bacterial activity
(Padmavathi et al., 2010)
2,5-Disubstituted-1,3,4-
oxadiazole derivatives
Anti-bacterial activity
(Jha et al., 2010)
2-(Biphenyl-4-yl)-5-aryl-1,3,4-
oxadiazole derivatives
Anti-bacterial activity
(Kumar et al., 2013)
5-(2-amino-3-pyridyl)-2-thioxo- 3H-
1,3,4-oxadiazole derivatives
Anti-cancer activity
(Liszkiewicz et al., 2003)
2-(1,3,4-triphenylpyrazol-5-yl)- 5-
phenyl-1,3,4-oxadiazole
Anti-cancer activity
(Mansour et al., 2003)
2-(4-chlorophenyl)-5-aryl-1,3,4-
oxadiazole derivatives
Anti-cancer activity (Ahsan et al., 2013)
5-pyridyl-1,3,4-oxadiazole-2- thiol
Anti-inflammatory activity
(Khan et al., 2004)
2,4-dichlorophenyl-5-(2,4,6-
trichlorophenoxymethyl)1,3,4-
oxadiazole
Anti-inflammatory activity
(Amir et al., 2007)
2,substituted-5-(2-
benzylthiophenyl)-1,3,4-
oxadiazoles
Anti-convulsant activity
(Almasirad et al., 2004)
2,substituted-5-[2-(2-
fluorophenoxy)phenyl]-1,3,4-
oxadiazoles
Anti-convulsant activity (Zarghi et al., 2005)
Aryl sulfonamido-5-[2’-
(benzimidazol-2’’-yl)]-1,3,4-
oxadiazoles
Anti-tubercular activity
(Kagthara et al., 1999)
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MATERIALS AND METHODS
The apparatus used for the research purpose is given
below:
Measuring cylinder
Beakers
Pipettes
Iodine flask
Magnetic stirrer
Glass rod
Round bottom flask (250ml, 100ml)
Condenser
Capillaries
Funnels
Viols
Separating funnels
Reagent bottles
Spatula
TLC card
Filter paper
Aluminum foil
Chemicals and reagents
The chemicals which were used for research purpose
are:
4-Fluorobenzoic acid
n-hexane
Ethyl acetate
Methanol
Absolute Ethanol
Chloroform
Diethyl Ether
Sulfuric acid (H2SO4)
Hydrazine hydrate
Carbon disulphide (CS2)
KOH
NaOH
Na2CO3
Hydrochloric acid (HCL)
DMF
LiH
Bromoacetyl bromide
Aniline
2-Ethyl aniline
2-Chloro aniline
3-Chloro aniline
4-Ethyl aniline
3-Methyl aniline
2-Ethoxy aniline
2,5-Dimethyl aniline
2,3-dimethyl aniline
2-Methyl aniline2-Bromo aniline
2-Methyl,6-Ethyl aniline
3-NO2 aniline
3,5-dimethyl aniline
Instruments used
For research work instruments that were used are
given below:
Electric Balance, UV lamp, Rotary Vacuum
evaporator, Microwave oven, Hot plate, FT-IR
Solvent purification
Methanol
CaO was used for purifying methanol i.e. for
removing water from methanol. 1 liter
of methanol was taken into a round bottom flask
(500ml). CaO was added and kept it
overnight. Distillation of methanol was done at 69 C.
Dry DMF
DMF was taken into a round bottom flask of required
capacity & is allowed to boil by
placing it on hot plate until it started evaporating. To
keep the DMF water free sodium
sulphate was added to the bottle after boiling DMF.
Absolute ethanol
In order to purify ethanol, CaO was used. One liter of
ethanol was taken into the
round bottom flask of 500 ml and was subjected to the
CaO and left for night. Temperature
for distillation of ethanol was set to about 78C.
General procedure
Reaction progress was checked by using pre-coated
silica gel aluminium packed thin
layer plates with the help of ethyl acetate & n-hexane
that will serve as mobile phase.
Melting points were checked by using melting point
apparatus & open capillaries.
Synthesis of 4-fluorobenzoate from 4-fluorobenzoic
acid (1)
Procedure
4-fluorobenzoic acid (15g) was taken in a round
bottom flask (250ml) and dissolved in 60ml of
absolute Ethanol. Then 7.5ml of H2SO4 was added
and shake it well. A condenser was used to reflux it
for7-8 hrs. The progress of reaction was monitored
from time to time by using Ethyl acetate and n-hexane
with the help of TLC. The gradual completion of
reaction was checked. The final product formation i.e.
4-fluorobenzoatee and its purity was checked by TLC
& observing it under UV lamp. After the completion
of reaction 5ml of 10% solution of Na2CO3 was
added to remove un-reacted acid. Then chilled water
was added and rested it for some time to perform
solvent extraction as ester of 4-fluorobenzoic acid is
not solid.
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Solvent extraction procedure
10% solution of Na2CO3 was added and pH was
maintained at 9. Then chloroform was added and
whole solution was transferred into separating funnel.
Shake it well and rest for almost 20 minutes until two
layers get separated. Then denser ester layer was
separated from bottom, chloroform was evaporated
by rotary vacuum evaporator and liquid ester was
obtained with yield 80%.
Formation of 4-fluorobenz hydrazide (2)
Procedure
The synthesized ester (12.5ml) was taken into a round
bottom flask (250ml), 50ml of absolute ethanol &
37.5ml of hydrazine hydrate was added in the flask.
The ester, ethanol & hydrazine hydrate for the
synthesis of hydrazide must be in following ratio:
Ester: Absolute ethanol: Hydrazine hydrate
1 : 4 : 3
Then round bottom flask was covered with aluminium
foil, placed on hot plate & allowed to stir it for almost
12-15 hrs. As the solid product appeared, reaction
completion was checked by performing TLC using n-
hexane, ethyl acetate & TLC cards & observed under
UV lamp.
After completion of reaction n-hexane was added.
Solution filtered as needle like crystals appeared.
Allowed it to dry & a shiny off white product was
obtained that was hydrazide & product was calculated
(79%).
1,3,4-oxadiazole synthesis (3)
Procedure
A solution of potassium hydroxide (4 pellets) was
made in absolute ethanol (40ml) & poured into a
round bottom flask. 10g of prepared hydrazide and
10ml of carbon disulphide was added in the round
bottom flask. Condenser was adjusted and allowed to
reflux for 6-8
hours. Reaction progress was checked at regular
intervals by using TLC procedure with the use of
varying ratio of n-hexane & ethyl acetate. As the
reaction got completed, 20ml of chilled distilled water
and a very small amount of dil. Sulfuric acid (H2SO4)
to maintain the pH 2-3 in order to remove un-reacted
base. Solid precipitates were obtained on vigorous
shaking and filtered. Product was dried, collected
&calculated.
Common scheme for amide formation
Chemicals used
Aniline (0.1 ml/0.05g)
Bromoacetyl bromide (0.1 ml)
Distilled water
10% solution of sodium carbonate
Procedure
0.1ml of aniline (for liquid anilines) & 0.05g (for solid
anilines) was taken in an iodine flask (250ml). Freshly
prepared 10ml solution of 10% of Na2CO3 was added
into the iodine flask and mixed it. Solution attains pH
approximately 8-9 & becomes basic. Mix it well and
acid was added slowly. Cover the flask with lid and
shake it well until precipitates begain to appear.
Reaction was shaken for another 20 minutes to obtain
fine precipitates and filtered. Product formed is an
amide of respective aniline and is dried. Purity of
product was checked by TLC.
Formation of 2-bromo-N-(2,3-dimethylphenyl)
acetamide
Chemicals
2,3-dimethyl aniline
Bromoacetyl bromide
Distilled water
10% solution of Na2CO3
Procedure
A clean iodine flask of 250 ml was taken. 10ml
solution of freshly prepared 10% solution of sodium
carbonate was added to the flask followed by the
addition of 0.1 ml of 2,3-dimethyl aniline. Shake the
flask to mix it properly. Then bromoacetyl bromide
was added gradually. Again shake it vigorously until
ppts appeared. Precipitates were filtered and proper
washing was done. Dry the precipitates and product
purity was checked by TLC.
3.5.2 Preparation of 2-bromo-N-(2,5-
dimethylphenyl) acetamide
Chemicals
2,5-dimethyl aniline
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Bromoacetyl bromide
Distilled water
10% solution of sodium carbonate
Procedure
Wash the round bottom flask properly and rinse with
distilled water. Add 10 ml of 10%
solution of sodium carbonate in round bottom flask
and 0.1 ml of 2,5-dimethyl aniline. Shake
it well to mix it evenly. Gradually add 1 ml 0f acid in
the flask and shake it vigorously. Filter
the reaction as the precipitates appeared. Precipitates
were dried and confirmed by
performing TLC. Amount of obtained product was
calculated and saved.
Synthesis of 2-bromo-N-(2-
methylphenyl)acetamide
Chemicals used
2-methyl aniline
Bromoacetyl bromide
Distilled water
10% solution of sodium carbonate
Procedure
10 ml solution of prepared 10% sodium carbonate was
added in a neat round bottom flask of 250ml. Then 0.1
ml of 2-methyl phenyl amine was added with the help
of pipette and shake gently to mix it. Acid was added
slowly and again shake to obtain precipitates. Filter it
on getting precipitates. Dry it and check its purity. The
solid product was then calculated and saved properly.
Formation of 2-bromo-N-(2-
bromophenyl)acetamide
Chemicals used
2-bromo aniline
Bromoacetyl bromide
Distilled H2O
10 % solution of Na2CO3 10 ml
Procedure
A washed round bottom flask was taken and 10 ml of
10 % sodium carbonate solution was poured.0.1 ml of
2-bromo aniline was dispersed into the flask and was
shaken properly. Then 1 ml of acid titled acid was
added and shaken it vigorously until ppts appeared.
Reaction mixture was filtered to separate the
precipitates formed. Precipitates were dried and solid
product obtained was calculated.
Synthesis of 2-bromo-N-(2-methyl,6-ethylphenyl)
acetamide
Chemicals used
2-methyl,6-ethyl aniline
Bromoacetyl bromide
Distilled water
10% solution of sodium carbonate
Procedure
A properly cleaned iodine flask was taken and 10 ml
solution of 10 % sodium carbonate was added. After
that 0.1 ml of 2-methyl,6-ethyl phenyl amine was
poured and shaking of reaction was done for 2-3
minutes at room temperature. Then bromoacetyl
bromide was added safely and shaking was done for
another 10 minutes or more according to reaction
conditions. Precipitates then obtained were filtered
and purity was checked. Solid precipitates were
collected and weighed.
Formation of 2-bromo-N-(3-
nitrophenyl)acetamide
Chemicals used
3-nitro aniline (0.05g)
Bromoacetyl bromide
Distilled water
10 % solution of sodium carbonate
Procedure
0.05g of solid 3-nitro aniline was weighed on
weighing balance and then transferred
to a clean iodine flask of 250 ml in which 10 ml
solution of 10% sodium carbonate was already
present. Mix the reaction mixture so that solid aniline
got dissolved in Na2CO3 solution evenly. After that
bromoacetyl bromide was added gradually and shaken
vigorously for 10 minutes to prepare solid precipitates
which were filtered later with proper washing. Solid
precipitates were collected, weighed and saved.
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Synthesis of 2-bromo-N-(3,5-dimethylphenyl)
acetamide
Chemicals used
3,5-dimethyl aniline
Bromoacetyl bromide (1 ml)
Distilled water
10 % solution of sodium carbonate
Procedure
10 ml freshly prepared solution of 10 % sodium
carbonate was added in a clean round bottom flask
rinsed with distilled water followed by the addition of
0.1 ml of 3,5-dimethyl aniline. Mix it properly and 1
ml of acid was added safely with the help of pipette
into the flask. Shake it well so that precipitates
appeared. Filter the ppts by using filter paper and
wash the product with distilled water properly. Dry
the ppts, collect them, weigh them and
save.
Preparation of 2-bromo-N-(2-
ethoxyphenyl)acetamide
Chemicals used
2-ethoxy aniline (0.1 ml)
Bromoacetyl bromide (1 ml)
Distilled water
10 % solution of sodium carbonate
Procedure
A clean iodine flask rinsed with distilled water was
taken and addition of 10 ml solution of 10 % sodium
carbonate was done. Then 0.1 ml of 2-ethoxy aniline
was poured and mixed evenly. Then slow and safe
addition of acid was done and shaken properly until
ppts of acetamide appeared. Filter it and dry the ppts.
Confirmation of reaction was checked by performing
TLC. Solid product then obtained was weighed and
kept.
Synthesis of 2-bromo-N-(3-
chlorophenyl)acetamide
Chemicals used
3-chloro aniline
Bromoacetyl bromide
Distilled water
10% solution of Na2CO3
Procedure
A clean iodine flask of 250 ml was taken. 10ml
solution of freshly prepared 10% solution of sodium
carbonate was added to the flask followed by the
addition of 0.1 ml of 3- chloro aniline. Shake the flask
to mix it properly. Then bromoacetyl bromide was
added gradually. Again shake it vigorously until ppts
appeared. Precipitates were filtered and proper
washing was done. Dry the precipitates and product
purity was checked by TLC. Amount
was calculated & packed.
Synthesis of 2-bromo-N-(2-ethylphenyl)acetamide
Chemicals used
2-ethyl aniline
Bromoacetyl bromide
Distilled water
10% solution of sodium carbonate
Procedure
Wash the round bottom flask properly and rinse with
distilled water. Add 10 ml of 10% solution of sodium
carbonate in round bottom flask and 0.1 ml of 2-ethyl
aniline. Shake it well to mix it evenly. Gradually add 1
ml 0f acid in the flask and shake it vigorously. Filter
the reaction as the precipitates appeared. Precipitates
were dried and confirmed by performing TLC.
Amount of obtained product was calculated and saved.
Synthesis of 2-bromo-N-(4-ethylphenyl)acetamide
Chemicals used
4-ethyl phenyl amine
Bromoacetyl bromide
Distilled water
10% solution of sodium carbonate
Procedure
10 ml solution of prepared 10% sodium carbonate was
added in a neat round bottom flask of 250ml. Then 0.1
ml of 4-ethyl phenyl amine was added with the help of
pipette and shaken gently to mix it. Acid was added
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slowly and again shake to obtain precipitates. Filter it
on getting precipitates. Dry it and check its purity. The
solid product was then calculated and saved properly.
Synthesis of 2-bromo-N-phenyl aetamide
Chemicals used
Aniline
Bromoacetyl bromide
Distilled water
10% solution of sodium carbonate
Procedure
A clean iodine flask rinsed with distilled water was
taken and addition of 10 ml solution of 10 % sodium
carbonate was done. Then 0.05g of aniline was poured
and mixedevenly. Then slow and safe addition of acid
was done and shaken properly until ppts of acetamide
appeared. Filtered it and dried the ppts. Confirmation
of reaction was checked by performing TLC. Solid
product then obtained was weighed and kept.
Synthesis of 2-bromo-N-(3-
methylphenyl)acetamide
Chemicals used
3-methyl aniline
Bromoacetyl bromide
Distilled water
10% solution of sodium carbonate
Procedure
A properly cleaned iodine flask was taken and 10 ml
solution of 10 % sodium
carbonate was added. After that 0.1 ml of 4-ethyl
aniline was poured and shaking of reaction
was done for 2-3 minutes at room temperature. Then
bromoacetyl bromide was added safely
and shaking was done for another 10 minutes or more
according to reaction conditions.
Precipitates then obtained were filtered and purity was
checked. Solid precipitates were
collected and weighed.
Synthesis of N-substituted 2[5-(4-
fluorophenyl)1,3,4-oxadiazol-2-yl-sulfanyl]Nphenyl
Acetamide
Chemicals used
5-(4-fluorophenyl)-1,3,4-oxadiazole-2-thiol (0.1g)
DMF (3-4 ml)
LiH (0.05g)
2-bromo-N-phenyl acetamide (0.09g)
Distilled water
n-hexane
Ethyl acetate
Procedure
A neat round bottom flask was taken. Synthesized and
weighed 5-(4-fluorophenyl)-
1,3,4-oxadiazole-2-thiol(0.1g) was added to the round
bottom flask also with the addition of
3-4 ml DMF and catalyst LiH. It was allowed to stir
for about half an hour. After 30 minutes
stirring 2-bromo-N-phenyl acetamide was added and
placed to continuous stirring. The reaction progress
was monitored properly. After completion of reaction
workup was done by
adding chilled water. Precipitates were filtered,
washed properly, dried and purity was
checked. Then obtained product was saved for further
analysis.
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Synthesis of N-substituted 2[5-(4-
fluorophenyl)1,3,4-oxadizol-2-yl-sulfanyl]-N-(3-
methylphenyl) acetamide
Chemicals used
5-(4-fluorophenyl)-1,3,4-oxadiazole-2-thiol
DMF (3-4 ml)
LiH (0.05g)
2-bromo-N-(3-methylphenyl)acetamide
Distilled water
n-hexane
Ethyl acetate
Procedure
A properly washed round bottom flask of 50 ml was
taken & o.1g of synthesized 5-
(4-fluorophenyl)-1,3,4-oxadiazole-2-thiol was added.
Then 3-4 ml of dimethylformamide
was poured into the round bottom flask followed by
the addition of 0.05g of lithium hydride
and allowed to stir for about 30 minutes at room
temperature. LiH acts as a catalyst in this
reaction. 0.09g of prepared 2-bromo-N-(3-
methylphenyl) acetamide was weighed and
transferred to the reaction mixture, covered the mouth
of round bottom flask with aluminium
foil and allowed to continuous stirring. Confirmation
of reaction was checked by TLC. After
completion of reaction chilled distilled water is added
and placed for stirring until ppts
appeared. Reaction mixture was filtered and dried.
Purity is again checked by TLC. The solid
product is collected, weighed and saved
Synthesis of N-substituted 2[5-(4-
fluorophenyl)1,3,4-oxadizol-2-yl-sulfanyl]-N-(2-
chlorophenyl) acetamide
Chemicals used
5-(4-fluorophenyl)-1,3,4-oxadiazole-2-thiol
DMF (3-4 ml)
LiH (0.05g)
2-bromo-N-(2-chlorophenyl)acetamide
Distilled water
n-hexane
Ethyl acetate
Procedure
0.1g of 5-(4-fluorophenyl)-1,3,4-oxadiazole-2-thiol
was taken in a properly washed
and dried round bottom flask of 50ml. Then 3-4ml of
DMF was added followed by addition
of lithium hydride and allowed for stirring for about
30 minutes. Then 0.09g of synthesized
2-bromo-N-(2-chlorophenyl) acetamide was added
and started stirring. Progress of reaction
was checked time to time by TLC with the help of n-
hexane and ethyl acetate in different
ratios. As reaction got completed chilled distilled
water added up to neck and again started
stirring until ppts became visible. Then ppts were
filtered, dried, calculated and saved for
further activities.
Biological activities
Activities of newly synthesized compounds were
monitored against microbes in opposition to
antibacterial and antifungal strains. All the strains
used were collected from pharmaceutical institute of
Lahore. Microorganisms were cultured and facilitated
with a
fundamental growth medium. Ager medium was rich
in gelatinous material which gave the bacteria
excellent medium for growth. Each bacterium was
provided a suitable environment nutrient and culture
medium for rapid growth. The temperature was set at
37C which is the best suitable temperature for
bacterial growth and to establish long colonies.
Disk diffusion method
A well known method i.e. disk diffusion method was
used to monitor the antimicrobial activity of newly
synthesized compounds. In this method the body fluid
of individual under study was placed onto filter paper
and then placed into potato dextro medium. After that
plates were placed under incubation for about 24h by
maintaining temperature at 35-37C. For checking anti-
microbial activity temperature was set at about 4C
while for examining anti-fungal activity it was 28C for
24h. Then growth of inhibition was measured by
measuring diameter.
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10
RESULT AND DISCUSSION
4-fluoro benzoate
Color
Brownish liquid
TLC spot
Single
Molecular weight
167
Molecular formula
C
9
H
9
FO
2
Melting point
124-127C
% yield
80%
IR Analysis
The characteristic peaks of 4-fluorobenzoate were
obtained at 1601.78 cm-1 for N-H bending,
2983.61cm-1 of alkane stretching, 1715.58 cm-1 of
C=O, at 605.35 cm-1 for C-Br and C-O str. at 1268.55
cm-1. These peaks ensured the presence of ester with
the existence of carbonyl in molecule. Analysis
confirmed the structure of 4-fluorobenzoate.
4-fluorobenzo hydrazide
Colour
White shinny powder
TLC spot
Single
Molecular wt.
153
Molecular formula
C
7
H
7
N
2
FO
Melting point
142-146
% yield
79%
IR Analysis
The characteristic peaks of 4-fluorobenzoate were
obtained at 3300.56cm-1 for N-H, 3014.97cm-1 of
alkane stretching, at 3195.52 for O-H str. and C-O at
1240.16cm-1. These peaks ensured the presence of
hydrazide with the existence of carbonyl in molecule.
Analysis
confirmed the structure of 4-fluorobenzo hydrazide.
5-(4-fluorobenzyl 1,3,4-oxadiazole)-2-thiol
Colour
White ppts
TLC spot
Single spot
Molecular wt.
211
Molecular formula
C
8
H
5
N
2
OSF
Melting point
210-215C
% yield
80%
IR Analysis
The characteristic peaks were obtained at 2945.12cm-
1 for C-H methylene, for C=C at 830.37cm-1, O-H at
2766.37cm-1 and N-O at 1511cm-1. Presence of these
peaks confirmed the five membered oxadiazole ring &
amidic carbonyl assembly in molecule. Considering
the
fundamental analysis the structure was designed as 5-
{(4-fluorobenzyl 1,3,4-oxadiazole)-2-thiol.
2-(5-(4-fluorophenyal)-1,3,4-oxadiazole-2-yl-
sylfanyl)-N-(2,3-
dimethylphenyl)acetamide
Colour
Off white
TLC spot
Single
Molecular formula
C
19
H
18
FN
3
O
2
S
Molecular wt.
370
Melting point
270-273
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%yield
78%
IR Analysis
The characteristics peaks for 2-(5-(4-fluorophenyl)-
1,3,4-oxadiazole-2-sulfanyl)-
N(2,3dimethylphenyl)acetamide were observed at
3058.71 cm-1 for C-H, at 2924cm-1 for O-H, for C-Cl
at 847cm-1 and for C-O at 1208.88cm-1. These peaks
and their study revealed the presence of five
membered oxadiazole ring and amidic carbonyl
assembly in molecule. On the basis of analysis the
name 2-(5-(4-fluorophenyl)-1,3,4-oxadiazol-2-yl-
sulfanyl)-N-(2,3-
dimethylphenyl)acetamide was awarded to it.
2-(5-(4-fluorophenyal)-1,3,4-oxadiazole-2-yl-
sylfanyl)-N-(2-
methylphenyl)acetamide
Colour
Light pinkish
TLC spot
Single
Molecular wt.
370
Molecular formula
C19H18FN3O2S
Melting point
290-293
%yield
78%
IR Analysis
The characteristics peaks for 2-(5-(4-fluorophenyl)-
1,3,4-oxadiazole-2-sulfanyl)-N-(2
methylphenyl)acetamide were observed at 3281 cm-1
for N-H, at 1664.86cm-1 for C=N, 1501.52 of N-
Ocm-1, for C-Cl str. at 692.58cm-1 and for C=C at
885cm-1. These peaks and their study revealed the
presence of five membered oxadiazole ring and
amidic carbonyl assembly in molecule. On the basis of
analysis the name 2-(5-(4-fluorophenyl)-1,3,4-
oxadiazol-2-yl-sulfanyl)-N-(2-
methylphenyl)acetamide was awarded to it.
2-(5-(4-fluorophenyal)-1,3,4-oxadiazole-2-yl-
sylfanyl)-N-(2-
bromophenyl)acetamide
Colour
Ash white
TLC spot
Single
Molecular formula
C17H14FN3O2S
Molecular wt.
422
IR Analysis
The characteristics peaks for 2-(5-(4-fluorophenyl)-
1,3,4-oxadiazole-2-sulfanyl)-N-(2-
bromophenyl)acetamide were observed at 3068cm-1
for C-H, 1618cm-1 of C=O, for C-N at 3266cm-1, for
C-S str. at 830cm-1 and for C-Br at 823cm-1. These
peaks and their study revealed the presence of five
membered oxadiazole ring and amidic carbonyl
assembly in molecule. On the basis of analysis the
name 2-(5-(4-fluorophenyl)-1,3,4-oxadiazol-2-
ylsulfanyl)-N-(2-bromophenyl)acetamide was
awarded to it.
2-(5-(4-fluorophenyal)-1,3,4-oxadiazole-2-yl-
sylfanyl)-N-(2-methyl,6-
ethylphenyl)acetamide
Colour
Off white
TLC spot
Single
Molecular formula
C
20
H
20
FN
3
O
2
S
Molecular wt.
384
Melting point
320-328
%yield
91%
IR Analysis
The characteristics peaks for 2-(5-(4-fluorophenyl)-
1,3,4-oxadiazole-2-sulfanyl)-N-(2-methyl,6-
ethylphenyl)acetamide were seen at 3071cm-1 for C-
H, for N-H at3269 cm-1, for C-H stretching of
methylene at 2931cm-1, C-N at 2361cm-1 and for C-F
at 1287cm-1. These peaks and their study revealed the
presence of five membered oxadiazole ring and
amidic carbonyl assembly in molecule. On the basis of
analysis the name 2-(5-(4-fluorophenyl)- 1,3,4-
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12
oxadiazol-2-yl-sulfanyl)-N-(2-methyl,6-
ethylphenyl)acetamide was given to it.
2-(5-(4-fluorophenyl)-1,3,4-oxadiazole-2-yl-
sulfanyl)-N-(3,5-
dimethylphenyl)acetamide
Colour
Light pinkish
TLC spot
Single
Molecular wt.
370
Molecular formula
C
19
H
18
FN
3
O
2
S
Melting point
269-271
%yield
71%
IR Analysis
The characteristics peaks for 2-(5-(4-fluorophenyl)-
1,3,4-oxadiazole-2-sulfanyl)-N-(3,5
dimethylphenyl)acetamide were observed at 3257 cm-
1 for N-H, at 3071cm-1 for C-H, for C=O at 1731cm-
1, for C-F at 1499cm-1. These peaks and their study
revealed the presence of five membered oxadiazole
ring and amidic carbonyl assembly in molecule. On
the basis of analysis the name 2-(5-(4-fluorophenyl)-
1,3,4-oxadiazol-2-yl-sulfanyl)-N-(3,5-
dimethylphenyl)acetamide was awarded to it.
2-(5-(4-fluorophenyal)-1,3,4-oxadiazole-2-yl-
sylfanyl)-N-
(2ethoxyphenyl)acetamide
Colour
Off white
TLC spot
Single
Molecular wt.
356
Molecular formula
C
18
H
16
FN
3
O
2
S
Melting point
206-208
% yield
70%
IR Analysis
IR analysis revealed the presence of characteristic
peaks at 2366.58 for C=C=O stretching, at 1459.24 for
O-H stretching, at 1254.11 for C-O, at 845 for C-Cl
bond str., at 761.66 for C-H. These peaks confirmed
the presence and structure of desired compound 2-(5-
(4-fluorophenyal)-1,3,4-oxadiazole-2-yl-sylfanyl)-N-
(2ethoxyphenyl)acetamide.
2-(5-(4-fluorophenyal)-1,3,4-oxadiazole-2-yl-
sylfanyl)-N-(3-
chlorophenyl)acetamide
Colour
Yellowish white
TLC spot
Single
Molecular formula
C17H14FClN3O2S
Molecular wt.
377
Melting point
291-293
%yield
80%
IR Analysis
The characteristics peaks for 2-(5-(4-fluorophenyl)-
1,3,4-oxadiazole-2-sulfanyl)-N-(3-
chlorophenyl)acetamide were observed at 3068cm-1
for C-H, 2359cm-1 of C-N, for N-H at 3266cm-1 and
for C-Br at 823cm-1. These peaks and their study
revealed the presence of five membered oxadiazole
ring and amidic carbonyl assembly in molecule. On
the basis of analysis the name 2-(5-(4-fluorophenyl)-
1,3,4-oxadiazol-2-yl-sulfanyl)-N-(3-
chlorophenyl)acetamide was awarded to it.
2-(5-(4-fluorophenyal)-1,3,4-oxadiazole-2-yl-
sylfanyl)-N-(2-
ethylphenyl)acetamide
Colour
Light yellow
TLC spot
Single
Molecular wt.
356
Molecular formula
C18H20FN3O2S
Melting point
201-203
IR Analysis
IR analysis revealed the presence of characteristic
peaks at 2876 for N-H stretching,
at 1477 for C-H bending, at 1651 for C=N, at 3258 for
0-H str., at 2051 for C=N and at 843
for C-Cl. These peaks confirmed the presence and
structure of desired compound 2-(5-(4-
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fluorophenyal)-1,3,4-oxadiazole-2-yl-sylfanyl)-N-(2-
ethylphenyl)acetamide.
2-(5-(4-fluorophenyal)-1,3,4-oxadiazole-2-yl-
sylfanyl)-N-(4-
ethylphenyl)acetamide
Colour
Light yellow
TLC spot
Single
Molecular wt.
356
Molecular formula
C
18
H
20
FN
3
O
2
S
Melting point
201-203
% yield
75%
IR Analysis
IR analysis revealed the presence of characteristic
peaks at 3387 for N-H stretching, at 2987 for C-H
stretching, at 1669 for C=O, at 1292 for C-O-C bond
str., at 2051 for C=N, at 823 for C-F and at 515 for C-
S. These peaks confirmed the presence and structure
of
desired compound 2-(5-(4-fluorophenyal)-1,3,4-
oxadiazole-2-yl-sylfanyl)-N-(4-
ethylphenyl)acetamide.
2-(5-(4-fluorophenyl)-1,3,4-oxadiazol-2-yl-
sulfanyl)-N-phenyl
Acetamide
Colour
Off white
TLC spot
Single
Molecular formula
C
18
H
15
FN
3
O
2
S
Molecular wt.
355
Melting point
298-300
%yield
79%
IR Analysis
The characteristics peaks for 2-(5-(4-fluorophenyl)-
1,3,4-oxadiazole-2-sulfanyl)-Nphenyl acetamide were
seen at 3131cm-1 for C-H, for N-H at3388 cm-1, for
C-N at 2359cm-1,
for C-O at 1288 and for C-F at 11157cm-1. These
peaks and their study revealed the presence of five
membered oxadiazole ring and amidic carbonyl
assembly in
molecule. On the basis of analysis the name 2-(5-(4-
fluorophenyl)-1,3,4-oxadiazol-2-yl-sulfanyl)-N-
acetamide was given to it.
2-(5-(4-fluorophenyl)-1,3,4-oxadiazole-2-yl-
sylfanyl)-N-(3-
methylphenyl)acetamide
Colour
Pinkish
TLC spot
Single
Molecular formula
C18H15FN3O2S
Molecular wt.
355
Melting point
275-278
%yield
77%
IR Analysis
The characteristics peaks for 2-(5-(4-fluorophenyl)-
1,3,4-oxadiazole-2-sulfanyl)-N-(3-
methylphenyl)acetamide were observed at 2708cm-1
for C-H, 1667 of C=Ncm-1, for O-H at 3242, for C-N
str. at 1310cm-1 and for C-Cl at 813cm-1. These
peaks and their study revealed the presence of five
membered oxadiazole ring and amidic carbonyl
assembly in molecule. On the basis of analysis the
name 2-(5-(4-fluorophenyl)-1,3,4-oxadiazol-2-
ylsulfanyl)-N-(3-methylphenyl) acetamide was
awarded to it.
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